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Challenges and Opportunities in Health Anxiety
Special Issue:
Challenges and Opportunities in Health Anxiety
Kathryn L. Lovero
Department of SociomedicalSciences, Columbia University Mailman School Public Health, New York, USA
Melissa A Stockton
Department of Psychiatry, University of Pennsylvania Perelman School Medicine, Philadelphia, USA
M Claire Greene
Program on Forced Migration and Health, Heilbrunn Department of Population and Family Health, Columbia University Mailman School of Public Health, New York, USA
Cale Basaraba
Department of Population Health, Grossman School of Medicine, New York University
Saida Khan
Department of Mental Health, Ministry of Health, Maputo, Mozambique
Dirceu Mabunda
Department of Mental Health, Ministry of Health, Maputo, Mozambique
Flavio Mandlate
Department of Mental Health, Ministry of Health, Maputo, Mozambique
Lidia Gouveia
Department of Mental Health, Ministry of Health, Maputo, Mozambique
Wilza Fumo
Department of Mental Health, Ministry of Health, Maputo, Mozambique
Melanie M Wall
Department of Psychiatry, New York State Psychiatric Institute and Columbia University Vagelos College of Physicians and Surgeons, New York, USA; Department of Biostatistics, Columbia University Mailman School of Public Health, New York, USA
Cristiane S Duarte
Department of Psychiatry, New York State Psychiatric Institute and Columbia University Vagelos College of Physicians and Surgeons, New York, USA
Maria A Oquendo
Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, USA
Milton L Wainberg
Department of Psychiatry, New York State Psychiatric Institute and Columbia University Vagelos College of Physicians and Surgeons, New York, USA
Abstract
Globally, mental and substance use disorders are a leading cause of disease burden. In low- and middle-income countries, where there is an extreme shortage of trained mental health specialists, validated, brief screening tools for mental and substance use disorders are required for non-specialists to efficiently identify patients in need of mental health care. Mozambique, one of the poorest countries in the world, has fewer than two mental health specialists for every 100,000 people. In the present study, we evaluated a comprehensive set of seven measures for depression, anxiety, somatization, alcohol use disorder, substance use disorder, psychosis and mania, and suicide risk among N=911 Mozambican adults in general healthcare settings. All instruments demonstrated acceptable internal consistency (α > 0.75). Compared to diagnoses made by the Mini International Neuropsychiatric Interview, all measures showed good criterion validity (AUC > 0.75), except the Psychosis Screening Questionnaire, which showed low sensitivity (0.58) for psychotic disorder. No substantial differences were observed in internal consistency when stratifying by gender, age, education level, primary language, facility-type, and patient status; criterion validity showed some variability when stratified by sub-population, particularly for education, primary language, and whether the participant was seeking care that day. Exploratory factor analyses indicated that the measures best differentiate categories of diagnoses (common mental disorder, severe mental disorders, substance use disorders, and suicide risk) rather than individual diagnoses, suggesting the utility of a transdiagnostic approach. Our findings support the use of these measures in Mozambique to identify common mental disorders, substance use disorders, and suicide risk, but indicate further research is needed to develop an adequate screen for severe mental disorders. Given the limited mental health specialists in this and other LMIC settings, these brief measures can support non-specialist provision of mental health services and promote closure of the treatment gap.
Deborah R. Gustafson
Department of Neurology, State University of New York Downstate Health Sciences University, Brooklyn, New York
Recai Yucel
Department of Biostatistics, Temple University, Philadelphia, Pennsylvania
Samuel Apple
State University of New York Downstate Health Sciences University, College of Medicine, Brooklyn, New York
Gianna Cirrone
State University of New York Downstate Health Sciences University, College of Medicine, Brooklyn, New York
Haoyuan Gao
Department of Biostatistics, Temple University, Philadelphia, Pennsylvania
Aaron Huang
State University of New York Downstate Health Sciences University, College of Medicine, Brooklyn, New York
Xinrui Ma
Department of Biostatistics, Temple University, Philadelphia, Pennsylvania
Ayesha Saad
State University of New York Downstate Health Sciences University, College of Medicine, Brooklyn, New York
Jeremy Wilson
State University of New York Downstate Health Sciences University, College of Medicine, Brooklyn, New York
Sarah Kabariti
Department of Emergency Medicine, Maimonides Medical Center, Brooklyn, New York; Department of Emergency Medicine, State University of New York Downstate Health Sciences University, Brooklyn New York
Sergey Motov
Department of Emergency Medicine, Maimonides Medical Center, Brooklyn, New York; Department of Emergency Medicine, State University of New York Downstate Health Sciences University, Brooklyn New York
Abstract
Background. Maintaining good mental health among Emergency Department healthcare workers (ED HCW) is paramount to well-functioning healthcare. We measured mental health and COVID-19 symptoms in ED HCW at a COVID-19 epicenter.
Methods. A cross-sectional, convenience sample of adult (>18 years) ED HCW in Brooklyn, New York, USA, who were employed at >50% of a full-time effort, was surveyed September–December, 2020 with reference period March-May 2020. An anonymous email-distributed survey assessed gender, age, race, healthcare worker status (clinical versus non-clinical), SARS-CoV-2 testing, number of people to talk to, COVID-19-related home problems, mental health care interruption during COVID-19, loneliness, and survey date. Outcomes included symptoms of depression, psychological distress, perceived stress, post-traumatic stress disorder (PTSD), anxiety, and resilience measured using validated scales.
Results. Of 774 HCW, 247 (31.9%) responded (mean age 38.2±10.8 years; 59.4% White; 52.5% men; 80.1% clinical; 61.6% SARS-CoV-2 tested). Average mental health scores were significantly higher among clinical vs non-clinical HCW (P’s<0.0001-0.019). The proportion reporting a clinically-relevant psychological distress symptom burden was higher among clinical vs non-clinical HCW (35.8% vs 13.8%, p=0.019); and suggested for depression (53.9% clinical vs 35.7% non-clinical, p=0.072); perceived stress (63.6% clinical vs 44.8% non-clinical, p=0.053); and PTSD (18.2% clinical vs 3.6% non-clinical, p=0.064). Compared to non-clinical staff, Medical Doctors and Doctors of Osteopathy reported 4.8-fold higher multivariable-adjusted odds of clinically-relevant perceived stress (95%CI 1.8-12.9, p=0.002); Emergency Medical Technicians reported 15.5-fold higher multivariable-adjusted odds of clinically-relevant PTSD (95%CI 1.6-150.4, p=0.018). Increasing age, number of COVID-19-related home problems and people to talk to, loneliness and mental health care interruption were adversely associated with mental health; being male and SARS-CoV-2 testing were beneficial.
Conclusions. COVID-19-related mental health burden was high among ED HCW in Brooklyn. Mental health support services are essential for ED HCW.
Elizabeth Armstrong-Mensah
Georgia State University School of Public Health, Atlanta, Georgia.
Maha Karim
Georgia State University School of Public Health, Atlanta, Georgia.
Oluwatoyosi Ogunmuyiwa
Georgia State University School of Public Health, Atlanta, Georgia.
Ernest Alema-Mensah
Morehouse School of Medicine, Department of Community Health and Preventive Medicine, Atlanta, Georgia.
Florence Darko
Georgia State University School of Public Health, Atlanta, Georgia.
Kritika Kolla
Georgia State University School of Public Health, Atlanta, Georgia.
Abstract
Objective: The study examined the mental health conditions experienced by working mothers as caregivers in Georgia, United States during the COVID-19 pandemic, the causes and outcomes of the mental health conditions experienced, and the coping mechanisms they employed.
Methods: A mixed methods cross-sectional study design was used to collect data from 132 working mothers in Georgia across six domains using Qualtrics. Quantitative data was analyzed using SPSS and SAS. Qualitative data was analyzed using a thematic approach.
Results: Working mothers experienced depression and anxiety while providing care during the pandemic. The lack of access to childcare and family support (12.5%), home schooling (18.1%), and juggling work and family (25.6%) contributed to the mental health conditions experienced, which led to anger (12.5%), aggression towards partners (11.3%), and the inability to sleep (18.8%). Coping mechanisms employed were drinking (1.3%), smoking (5.6%) and arguing with a spouse (8%).
Conclusion: While the pandemic affected the mental health of many adults in the US, working mothers providing care were among the population hardest hit. Although the immediate threat of COVID-19 has abated, its impact on mental health cannot be overlooked. By focusing primarily on the mental health of working mothers as caregivers during the pandemic, the study draws attention to, and underscores the need for targeted interventions and policies to be put in place to respond to the mental health needs of this population in the event of a future global health emergency.
Mayur N Mishra, BDS, MDS
Reader, Department Of Public Health Dentistry, K M Shah Dental College and Hospital, Sumandeep Vidhyapith (An institution deemed to be University), Piparia, Vadodara 391760, Gujarat, India.
Suchit Dana, BDS, MDS
Reader, Department of Periodontology, K M Shah dental college and hospital, Sumandeep Vidhyapith (An institution deemed to be University), Waghodia, Vadodara 391760, Gujarat, India.
Pranav Kurup
Senior Lecturer, Department Of Public Health Dentistry, K M Shah Dental College And Hospital, Sumandeep Vidhyapith (An institution deemed to be University), Piparia, Vadodara 391760, Gujarat, India.
Ubaid Kureshi
Senior Lecturer, Department Of Public Health Dentistry, K M Shah Dental College And Hospital, Sumandeep Vidhyapith (An institution deemed to be University), Piparia, Vadodara 391760, Gujarat, India.
Shiba Vijayan
Senior Lecturer, Department Of Public Health Dentistry, Vydehi institute of Dental science and research centre, Whitefield , Bangalore.
Nairuti Dave
General dental practitioner, Bhavnagar.
Abstract
Health workers are central to the COVID-19 pandemic response, balancing additional service delivery needs while preserving access to essential health services and deploying COVID-19 vaccines. They also face higher risks of infection in their efforts to protect the greater community and are exposed to hazards such as psychological distress, fatigue and stigma.
Methodology: A retrospective cross sectional study is carried out among the health care workers residing Gujrat, India. A cross sectional study was carried out among the sample of 600 registered health care workers,(specialist, general physian, nurses, others) who were active during covid pandemics. Online questionnaire (DASS 21 and Maslach burnout inventory) were distributed to the participants to evaluate their stress, anxiety and depression status.
Results: Around 48.1 % participants were suffering from mild-moderate to severe level of depression. Anxiety was found to effect around 60% of health care workers. And almost 68% of health care worker has suffered from stress. The burnout level was also very high among health care worker (table 5). It was found that 52% participants were having low-moderate to high level of burnout.
Conclusion: Stressfulness of work, and practice management were factors in which reality was experienced to be worse than expected. Also, finding a suitable practice was something that appeared more difficult than expected in their early career. Burnout is recognized as a potential problem within a broad range of occupations, and within many different countries.
van der Aa H.P.A
Amsterdam UMC, location Vrije Universiteit Amsterdam, Ophthalmology, De Boelelaan 1117, Amsterdam, The Netherlands/ Amsterdam UMC, location Vrije Universiteit Amsterdam, Public and Occupational health, De Boelelaan 1117, Amsterdam, The Netherlands
van Nassau F
Amsterdam UMC, location Vrije Universiteit Amsterdam, Public and Occupational health, De Boelelaan 1117, Amsterdam, The Netherlands / Amsterdam Public Health, Quality of Care, Mental Health, Aging and Later Life, Amsterdam, The Netherlands
Rozemeijer S.C.A.
Amsterdam UMC, location Vrije Universiteit Amsterdam, Ophthalmology, De Boelelaan 1117, Amsterdam, The Netherlands
Schakel W.
Amsterdam UMC, location Vrije Universiteit Amsterdam, Ophthalmology, De Boelelaan 1117, Amsterdam, The Netherlands / Amsterdam Public Health, Quality of Care, Mental Health, Aging and Later Life, Amsterdam, The Netherlands
van Rens G.H.M.B.
Amsterdam UMC, location Vrije Universiteit Amsterdam, Ophthalmology, De Boelelaan 1117, Amsterdam, The Netherlands
van Nispen R.M.A.
Amsterdam UMC, location Vrije Universiteit Amsterdam, Ophthalmology, De Boelelaan 1117, Amsterdam, The Netherlands / Amsterdam Public Health, Quality of Care, Mental Health, Aging and Later Life, Amsterdam, The Netherlands
Abstract
Purpose: Mental health problems are common in patients with macular oedema, who receive repeated intravitreal injections with anti-vascular endothelial growth factor. A guided internet-based self-help intervention, called E-PsEYE, was developed to reduce these problems. Patients were referred by their ophthalmologist to follow E-PsEYE individually at home, guided by a social worker from low vision services. Since e-mental health is new in this setting and professionals were collaborating in a novel way, barriers and facilitators during implementation and for future scale-up were evaluated.
Methods: Semi-structured interviews were performed with patients (n=8), ophthalmologists (n=4), heads of ophthalmology departments (n=2), doctor’s assistants (n=3), social workers (n=6) and managers from low vision services (n=2), and representatives from a health insurer (n=2). Data were analyzed using a thematic approach.
Results: Both patients and professionals were satisfied with the potential efficiency and added value of the intervention. They indicated that sufficient digital skills in patients and social workers, information technology (IT) support and adding personalized face-to-face contacts, could facilitate implementation. However, a high workload within the different settings (i.e., hospital and low vision services) and the reluctance of both patients and professionals in focusing on mental health problems could hinder implementation. Moreover, evidence on cost-effectiveness and incorporation in current guidelines were expected to be important for reimbursement and scale-up.
Conclusions: Both on the individual level and in the interaction between stakeholders and their context, different important barriers and facilitators were expressed. To facilitate the use of E-PsEYE in practice, strategies that focus on these aspects could be implemented, e.g. healthcare providers could discuss and normalize mental health complaints and their digital skills could be supported.
Georgia Konstantopoulou
Department of Educational Sciences and Social Work, University of Patras, Greece
Martha Toli
Department of Educational Sciences and Social Work, University of Patras, Greece
Maria Skondra
Department of Psychiatry, Faculty of Medicine, University of Patras, Greece
Marina Charalampopoulou
Department of Psychiatry, Faculty of Medicine, University of Patras, Greece
Panagiotis Felemegkas
Department of Psychiatry, Faculty of Medicine, University of Patras, Greece
Panagiotis Alexopoulos
Department of Psychiatry, Faculty of Medicine, University of Patras, Greece
Eliza Georgiou
Department of Psychiatry, Faculty of Medicine, University of Patras, Greece
Abstract
Background: This study investigates the influence of anxiety and anger on the brain health of primary school children and how these emotions manifest in daily life. While anxiety and anger are normal emotional responses, chronic experiences can impact both physical and psychological well-being.
Method: The study involved 96 primary school students from Patras, aged between eight and twelve, with younger grades excluded due to comprehension difficulties. Participants completed questionnaires assessing their health, physical activity, mood, and the frequency and intensity of anxiety and anger symptoms. Descriptive statistics were utilized to analyze the data.
Results: Among the participants, 56.25% were girls and 43.75% were boys. Most reported very good (51.04%) or excellent (33.33%) health. High levels of physical activity and substantial energy were common, with 54.17% being very active and 62.50% having a lot of energy. Positive moods predominated, though 57.29% sometimes felt angry and 76.04% rarely felt sadness. Physical symptoms of anxiety, such as stomach pain (51.04%) and tachycardia (40.63%), were prevalent.
Conclusion: The findings underscore the significant presence of anxiety and anger among children, highlighting their impact on physical symptoms and potential implications for brain health. Early intervention and support are essential to manage these emotions constructively. Addressing environmental and social factors that trigger anxiety and anger is crucial for fostering healthy emotional development and maintaining optimal brain health.
Ehiremhen Ozah
Urology Unit, Department of Surgery, Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria
Esteem Tagar
General Surgery Unit, Department of Surgery, Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria
William Akerele
Paediatric Surgery Unit, Department of Surgery, Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria
Abstract
Background: Coronavirus disease had a devastating effect on the World, with significant disruption in healthcare, the burgeoning impact is still unfolding. The inequities and fragilities amongst nations particularly low and medium economic countries whose patients are dependent on out of pocket expenditure to access healthcare, has occasioned varied consequence of the pandemic on patients in the health care setting and it has reshaped how health care is practiced.
Aims: The aim of this review article was to assess the impact of Coronavirus disease on health care utilization by non -COVID patient during the pandemic.
Methods: The review article was carried out with a search engine focused on articles related to impact of Coronavirus disease published between December 2019 till date, which were identified and reviewed.
Conclusion: The review article gave an insight to the significant disruptions in health care services amongst patients witnessed across countries of the world, the disparities in the disruptions were due to heterogeneity amongst nations, national policies and health policies during the pandemic and the socioeconomic realities that ensued. Outpatient services witnessed varying reduction across the globe ranging between 30-50%. Sub-Saharan Africa witnessed disruption as much as 50% depending on load of COVID-19 infection amongst populace. The reason for the interruptions across the world was the fear of contracting the disease, access to health care setting due to lock down and shortage of health care personnel, in addition in sub-Saharan Africa, the economic down turn occasioned by the pandemic reduced household income which in turn reduced expenditure on health since most countries were dependent on out of pocket expenditure to fund health care services.
In-patient care was also not spared of the disruptions witnessed even though emergency care was prioritized. Overall, there was a reported reduction in admissions for respiratory diseases due to non- pharmacological measures aimed at stemming COVID-19 infection which was equally effective for other respiratory diseases. In some countries like United States the reduction in hospital admissions was paralleled by increasing mortality particularly amongst Hispanic blacks as more acute and severe cases were deemed to have presented for admissions. Surgical priority was maintaining emergency services and prioritization of cancer care, there was a measurable reduction in surgical procedures as elective surgeries were postponed or cancelled. Most laparoscopic and endoscopic procedures were cancelled because of the perceived notion that they are aerosol generating and could increase transmission of COVID-19 infection from asymptomatic carriers, however US jettisoned cancellation of its surgical procedures after 35 days considering that it could not cope. The psychosocial impact of the pandemic and health care access spiraled into increasing anxiety and depression for both health care workers and patients, while the fear of stigmatization was rife from contracting the disease.
Thaisa Mara Leal Cintra Rodrigues
PhD student in Sciences at the University of São Paulo – Interunit Program at the Ribeirão Preto School of Nursing, Ribeirão Preto, São Paulo, Brazil.
Rita de Cássia de Marchi Barcellos Dal
Phd at the University of São Paulo at Ribeirão Preto College of Nursing, EERP-USP, Ribeirão Preto, São Paulo, Brazil.
Carla Aparecida Arena Ventura
Full Professor at the University of São Paulo at Ribeirão Preto College of Nursing, EERP-USP, Ribeirão Preto, São Paulo, Brazil.
Abstract
Background: The post-pandemic historical moment of COVID-19 has had consequences on the mental health of workers, evidenced by the growing statistics of depression, anxiety, suicidal ideation, panic syndrome, burnout syndrome, psychotic episodes, alcohol and drug addiction, stress, fatigue, and professional exhaustion.
Aims: Analyse the recommendations of the International Labour Organization and the Brazilian laws applicable to occupational mental health to identify documents that address intervening laws in workers’ mental health in the international scientific literature and introduce Bill 3,588/2020, which aims to regulate occupational psychosocial risks.
Methods: Narrative review of the scientific literature in the databases Scopus, Lilacs BVS, PubMed, Cinhal, and Ebesco and document analysis of Brazilian legislation and international recommendations on workers’ mental health and norms related to exposure to occupational psychosocial risks and measures of intervention in mental health.
Results: The International Labour Organization established three Conventions to protect workers’ health. In the Brazilian legal system, six broad and general norms were identified. The narrative prediction resulted in nine intervening laws that address the worker’s mental health. Conclusion: In Brazil, there is no specific legislation regarding the worker’s right to mental health, nor any regulation through Regulatory Norms, which demonstrates the need for the approval of Bill 3,588/2020, pending in the National Congress, which aims at regulating psychosocial risks, such as intervention, management, and prevention measures capable of minimizing mental illness at work.
Christine B. Weldon, MBA
The Center for Business Models in Healthcare
Brittani James, MD
University of Illinois at Chicago, UI Health Mile Square Health Center
Kimberly Jinnett, PhD, MSPH
Genentech
Caroline Solon, MSc
Genentech
Claire Thesing, MD
University of Illinois at Chicago, UI Health Mile Square Health Center
Judes Fleurimont
UI Health Mile Square Health Centers
Karriem S. Watson, DHS, MS, MPH
University of Illinois at Chicago, UI Health Mile Square Health Center
Julia R. Trosman, PhD, MBA
The Center for Business Models in Healthcare
Abstract
There is an under-addressed need to help patients who experience mild-to-moderate COVID-19 symptoms or are asymptomatic, to manage their disease at home. While no approved COVID-19 medical treatments exist for these patients, home-based self-management is crucial because it has the potential to relieve patients’ symptom burden and provide concrete actions that help mitigate anxiety, isolation and loss of personal control associated with the disease. Existing resources often provide a deluge of information, which may not be readily actionable by patients. Additionally, existing resources focus primarily on managing severe symptoms. A 4R COVID-19 toolkit was developed to address the unmet need for patients with mild or moderate COVID-19 symptoms based on expert discussions and a literature review. The toolkit applies the principles of the previously developed 4R Oncology Model of providing patients with a project plan for the course of their COVID-19 care, information on self-management of mild to moderate symptoms, and criteria for contacting their medical provider. The toolkit was developed with support from Genentech; it is not intended to substitute for the medical advice of a healthcare provider. The 4R COVID-19 toolkit continues to be improved as updated information is available via patient and clinician feedback, literature, and expert guidance. A copy of the current toolkit is attached to this paper for use and adaptation by care providers, practices, and institutions.
Maria Evandrou
ESRC Centre for Population Change, University of Southampton, Southampton, UK; Centre for Research on Ageing, University of Southampton, Southampton, UK
Jane Falkingham
ESRC Centre for Population Change, University of Southampton, Southampton, UK
Min Qin
ESRC Centre for Population Change, University of Southampton, Southampton, UK
Athina Vlachantoni
ESRC Centre for Population Change, University of Southampton, Southampton, UK; Centre for Research on Ageing, University of Southampton, Southampton, UK
Abstract
Objectives: The COVID-19 crisis significantly reshaped individuals’ daily lives and work, potentially also affecting their mental health. This study examines changes in psychological stress, anxiety, and depression during the first lockdown amongst five British cohorts at different stages of the life course: older adolescence, early adulthood, mid-career, and later life. It investigates the correlation between self-reported stress and life changes across a range of domains including health; education and the move to home schooling; working patterns and furlough; and living arrangements and family life.
Methods: The study analyses data from 14,130 cohort members participating in the special COVID-19 surveys conducted in May 2020. These surveys are part of the ongoing 1946, 1958, 1970, and 2000-01 British birth cohorts, as well as the Next Steps cohort (born in 1989-90). Probit regression models assess the likelihood of increased stress among individuals reporting pandemic-related life changes compared to those who did not, across a range of different life domains. The study also examines the association between heightened stress and subsequent anxiety and depression.
Results: The research highlights the diverse challenges faced by individuals at different life stages during the early phase of the pandemic. Young people faced disrupted education, with many returning to the parental home; parents had to cope with the closure of schools and childcare services, dealing with young children at home; mid-career professionals also found themselves balancing work and family responsibilities; retirees faced cancelled medical appointments and disrupted home care services. All these challenges were associated with significantly increased reported stress among affected individuals; particularly in adolescence and young adulthood, where mental health outcomes were poorer than in older cohorts. Moreover, heightened stress substantially raised the risk of developing anxiety and depression.
Conclusions: The study affirms that individuals in various life stages faced exceptional challenges during the initial lockdown, adversely affecting mental well-being. Adolescents and young adults, experiencing more life changes but lacking coping resources, felt the disruption especially heavily. Going forward, given the potential health consequences of prolonged stress, anxiety, and depression, policymakers must consider these temporary challenges through a life course lens when designing appropriate interventions and support services.
Abstract
Introduction: Childhood and adult trauma are common experiences in perinatal women worldwide. Psychological trauma has a well-documented effect on mothers’ mental health, but less is known about its impact on breastfeeding.
Objectives: This article synthesizes the results from recent studies on trauma on breastfeeding and perinatal mental health. I describe possible mechanisms by which trauma influences breastfeeding and mental health and provide practical suggestions for working effectively with this population.
Method: Studies were identified via searches in PubMed and PsychInfo. Key words were adverse childhood experiences, child abuse, child maltreatment, intimate partner violence, birth trauma, pregnancy, postpartum, breastfeeding, postpartum depression, postpartum anxiety, and posttraumatic stress disorder (PTSD). Preference was given to studies published in the past 5 years, but older studies were included if more recent studies were not available. Review articles were also included.
Results: Psychological trauma can affect anyone regardless of income, religion, country of origin, age, or race and ethnicity. Pregnant and postpartum women are no exception. Traumatic experiences can make breastfeeding more difficult, but it is often an important goal for trauma survivors. Some studies have found that trauma survivors are more likely to breastfeed. Breastfeeding may be particularly important for trauma survivors in that it lessens trauma symptoms, improves mental health, and lowers the risk of mothers maltreating their children. When working with trauma survivors, it is important that practitioners avoid making assumptions that mothers will not breastfeed. It is important to support their breastfeeding goals.
Clinical Implications: Providers who work with new mothers will likely encounter a substantial percentage who are trauma survivors. Trauma survivors may not share their stories with providers, even if they directly ask, but these mothers’ experiences can influence both breastfeeding and their mental health. Practitioners who understand trauma and support breastfeeding in a trauma-informed way can positively influence both breastfeeding and mental health outcomes. Both childhood and adult trauma can have a negative effect on breastfeeding, but the mechanism may vary. Recent trauma can directly impact hormones needed for breastfeeding whereas childhood trauma may impact it via trauma sequelae, such as depression, anxiety, and PTSD.
Giovana Cugini Sanches
Universidade de Taubaté (São Paulo – Brazil)
Juliana Santos de Lima
Universidade de Taubaté (São Paulo – Brazil)
Marcella Vizcaya Val Delatorre
Faculdade Israelita de Ciências da Saúde Albert Einstein (São Paulo – Brazil)
Abstract
Introduction: During the Covid-19 pandemic, a rise in symptoms of anxiety and depression was described in the general population. It’s critical to analyze these symptoms in the pediatric population, considering the influence of mental health across the social and academic domains, and its impact on neurodevelopment, morbidity, and mortality. This study aims to recognize and compare its risk factors, and suggest evidence-based policies to mitigate the adverse effects of future pandemics on youth.
Methodology: Using a search strategy through PubMed, CINAHL, and Scholar Google platforms, after screening 106 articles, 50 were read in full. After its analysis, 10 met the inclusion criteria of a publication date after March 2020, cross-section or cohort/case-control study with data including general pediatric population mental health or pediatric population infected with Covid-19 mental health.
Discussion: In the general pediatric population, isolation, higher time of screen use, and information restriction to one news vehicle were factors associated with the self-reported psychological distress. Nonetheless, the time spent exercising was suggested as a protection element. In the sociodemographic domain, older age, low socioeconomic status, migration background, and limited living space were associated with adverse mental health. Hospitalization and Long-Covid were risk factors associated with the pediatric population infected with the SARSCov-2.
Conclusion: It’s crucial to measure and discuss the impact of the Covid-19 pandemic on the mental health of vulnerable children and adolescents. Applicable interferences that showed less anxiety in hospitalized kids were contacting the family member through free teleconferencing programs and providing video games for children in isolation. There are still COVID-19 worldwide studies and data to be released, it’s a subject to continue its discussion, and formulation of evidence-based policies.
Stephanie F. Dailey
College of Education and Human Development, George Mason University, Fairfax, Virginia. 4400 University Drive MSN 1H1 Fairfax, VA 22030.
Abstract
This article explores the nuanced relationship between COVID-related stressors and mental health outcomes, with a particular focus on sociodemographic patterns and implications for practice. It illuminates the psychological impacts of the pandemic, explores sociodemographic disparities outcomes among historically marginalized communities, and offers recommendations for practitioners and policymakers to address mental health challenges. It reviews current research highlighting the direct correlation between pandemic-related stressors and heightened levels of depression, anxiety, and economic instability across diverse demographic groups, while also exploring the most widely reported barriers these communities face in accessing mental health services. Through a comprehensive review of the literature, key strategies for addressing mental health disparities emphasize the importance of promoting social connectedness and dispositional mindfulness as protective factors. By integrating culturally responsive interventions, promoting mental health literacy, building resilience and coping skills, strengthening support systems, and advocating for policy changes, this article contributes to efforts aimed at reducing mental health inequities and promoting equitable access to care for all individuals affected by the pandemic.
Elena Soto Vega
Escuela de Medicina, Universidad Anáhuac Puebla
Maria Fernanda Pérez Zepeda
Escuela de Medicina, Universidad Anáhuac Puebla
Eduardo Lome Gutierrez
Escuela de Medicina, Universidad Anáhuac Puebla
Maria del Carmen Cabrera Martinez
Escuela de Medicina, Universidad Anáhuac Puebla
Samia Julieta Gomez Gomez
Escuela de Medicina, Universidad Anáhuac Puebla
Sebastian Duno Caldera
Escuela de Medicina, Universidad Anáhuac Puebla
Abstract
The accessibility of online health information has changed the decision-making process for patients concerning their health. Nevertheless, concerns persist regarding the quality and reliability of the information available on the Internet. The Internet has emerged as the dominant global source of health-related information, with a significant proportion of individuals utilizing it to retrieve information on nutrition, diseases, symptoms, and treatment options. However, the unregulated nature of online health information poses challenges in terms of assessing its credibility and accuracy. Increasingly, patients are actively engaged in healthcare decision-making, empowered by the information they acquire online. Consequently, a paradigm shift from the traditional physician-centric model to a more collaborative and patient-centered approach has occurred. Patients now have access to an expanded array of healthcare professionals and possess the ability to make informed decisions regarding their treatment and care. Nonetheless, the variability in quality of online health information and patients’ limited capacity to effectively evaluate it can give rise to misunderstandings, misinformation, and an elevated propensity for self-diagnosis and self-treatment.
Furthermore, patients’ reliance on online information can impact the patient-physician relationship, with discrepancies between online findings and physician diagnoses leading to dissatisfaction and conflicts. Barriers obstructing effective patient-physician communication on online health information include patient’s apprehension about challenging physicians, perceived resistance from physicians themselves, and difficulties in comprehending and articulating the information sourced online. Addressing these barriers and enhancing the patient-physician relationship can yield positive outcomes, including timely diagnosis, effective treatment, and shared decision-making. While Internet use brings advantages such as increased accessibility to healthcare providers and enhanced patient empowerment, it also introduces certain disadvantages. The prevalence of misinformation and disinformation on the Internet engenders risks, contributing to confusion and a lack of trust in healthcare institutions. Additionally, patients may encounter challenges in interpreting and prioritizing the information they find online, which can result in heightened anxiety and uncertainty regarding their health. This review critically examines the impact of Internet use on patient decision-making and its effect on the patient-physician relationship.
Joseph Donnelly
Department of Public Health, Montclair State University
Elena Saldutti
Department of Public Health, Montclair State University
Abstract
This commentary provides a comprehensive overview of the influence of social media on the health and well-being of adolescents, focusing on emotional/mental health, self-esteem, alcohol and drug use, peer pressure, and both negative and positive influences. It highlights concerns about the potential negative impact of social media, including increased levels of anxiety, depression, and loneliness, as well as the impact on self- esteem through seeking validation and unrealistic comparisons. Furthermore, it discusses how social media exposes adolescents to content promoting alcohol and drug use and amplifies peer pressure, leading to potential substance abuse and negative decision-making. Despite these drawbacks, the abstract acknowledges the positive aspects of social media, such as providing social support, educational resources, and mental health awareness. It emphasizes that social media can be leveraged in the high school classroom to promote healthy behaviors. Strategies for responsible social media use, critical thinking skills, digital literacy, cyberbullying prevention, and content creation are suggested as ways to navigate the online world safely and foster positive online interactions. By understanding both the negative and positive impacts of social media, collectively we can guide adolescents in using social media in a way that promotes resilience, well-being, and healthy habits. Employing strategies that harness the positive aspects of social media, educators, parents, and society can play a pivotal role in helping adolescents navigate the digital landscape, promoting healthy behaviors, and fostering resilience in the face of online challenges.
Challenges and Opportunities in Aging
Special Issue:
Challenges and Opportunities in Aging
Hoost SS
Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, and the New York Presbyterian Hospital, New York, NY
Brickman AM
Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY; H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY; Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, and the New York Presbyterian Hospital, New York, NY
Manly JJ
Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY; G.H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY; Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, and the New York Presbyterian Hospital, New York, NY
Honig LS
Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY; G.H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY; Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, and the New York Presbyterian Hospital, New York, NY
Gu Y
Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY; G.H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY; Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, and the New York Presbyterian Hospital, New York, NY
Sanchez D
G.H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY; Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, and the New York Presbyterian Hospital, New York, NY
Reyes-Dumeyer D
Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY; H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY; Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, and the New York Presbyterian Hospital, New York, NY
Lantigua RA
Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY; H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY; Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, and the New York Presbyterian Hospital, New York, NY
Kang MS
Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY
Dage JL
Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN; Department of Neurology, Indiana University School of Medicine, Indianapolis, IN; Indiana Alzheimer’s Disease Research Center, Indiana University School of Medicine Indianapolis IN
Mayeux R
Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY; H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY; Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, and the New York Presbyterian Hospital, New York, NY
Abstract
Background: Comorbidities may influence the levels of blood-based biomarkers for Alzheimer’s disease (AD). We investigated whether differences in risk factors or comorbid conditions might explain the discordance between clinical diagnosis and biomarker classifications in a multi-ethnic cohort of elderly individuals.
Aims: To evaluate the relationship of medical conditions and other characteristics, including body mass index (BMI), vascular risk factors, and head injury, with cognitive impairment and blood-based biomarkers of AD, phosphorylated tau (P-tau 181, P-tau 217), in a multi-ethnic cohort.
Methods: Three-hundred individuals, aged 65 and older, were selected from a prospective community-based cohort for equal representation among three racial/ethnic groups: non-Hispanic White, Hispanic/Latino and African American/Black. Participants were classified into four groups based on absence (Asym) or presence (Sym) of cognitive impairment and low (NEG) or high (POS) P-tau 217 or P-tau 181 levels, determined previously in the same cohort: (Asym/NEG, Asym/POS, Sym/NEG, Sym/POS). We examined differences in individual characteristics across the four groups. We performed post-hoc analysis examining the differences across biomarker and cognitive status.
Results: P-tau 217 or P-tau 181 positive individuals had lower BMI than P-tau negative participants, regardless of symptom status. Symptomatic and asymptomatic participants did not differ in terms of BMI. BMI was not a mediator of the effect of P-tau 217 or P-tau 181 on dementia. Frequencies of other risk factors did not differ between the four groups of individuals.
Conclusions: Participants with higher levels of P-tau 217 or P-tau 181 consistent with AD had lower BMI regardless of whether the individual was symptomatic. These findings suggest that weight loss may change with AD biomarker levels before onset of cognitive decline. They do not support BMI as a confounding variable. Further longitudinal studies could explore the relationship of risk factors with clinical diagnoses and biomarkers.
Michael Leone
Institute for Aging Research, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA; Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA
Nir Barzilai
Institute for Aging Research, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA; Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA
Abstract
The biological mechanisms of aging drive the development of chronic diseases such as cardiovascular disease, diabetes, dementia, and cancer that dominate our current medical system. Geroscience-guided approaches seek to mitigate these pathological consequences of aging by targeting the fundamental hallmarks of aging. Using modalities that modulate these aging mechanisms to reinforce longevity we can prevent the onset of these diseases as well as target many of them at once. In this way, geroscience-guided approaches hope to extend both lifespan and healthspan in the near future. This article builds upon a previous paper which proposed a standardized process for evaluating FDA-approved medications for their geroscience potential and prioritized them to reflect preclinical and clinical evidence. In this article, we provide an update of the previous list of candidate gerotherapeutics to reflect the new and rapidly evolving evidence. We include the geroscience-guided evidence for three new FDA-approved drugs which did not have strong arguments for inclusion before: bisphosphonates, GLP-1 receptor agonists, beta blockers. This updated prioritization should help guide the efforts and financial investments for translating geroscience and allow immediate progress involving such candidate gerotherapeutics, especially the top 4 drugs: SGLT2 inhibitors, metformin, bisphosphonates, and GLP-1 receptor agonists. Since all of these drugs have been approved for safety and used extensively, repurposing them as gerotherapeutics should be considered in older adults.
Abstract
Although it is known that APOE genotype is the strongest genetic risk factor for late-onset Alzheimer’s disease, development is a multifactorial process. Alcohol use is a contributor to the epidemic of Alzheimer’s disease and related dementias in the US and globally, yet mechanisms are not fully understood. Carriers of the APOE ε 4 allele show elevated risk of dementia in relation to several lifestyle factors, including alcohol use. In this review, we describe how alcohol interacts with APOE genotype and aging with potential implications for Alzheimer’s disease promotion. Age-related immune senescence and “inflammaging” (i.e., low-grade inflammation associated with aging) are increasingly recognized as contributors to age-related disease. We focus on three immune pathways that are likely contributors to Alzheimer’s disease development, centering on alcohol and APOE genotype interactions, specifically: 1) microbial translocation and immune activation, 2) the senescence associated secretory phenotype, and 3) neuroinflammation. First, microbial translocation, the unphysiological movement of gut products into systemic circulation, elicits a proinflammatory response and increases with aging, with proposed links to Alzheimer’s disease. Second, the senescence associated secretory phenotype is a set of intercellular signaling factors, e.g., proinflammatory cytokines and chemokines, growth regulators, and proteases, that drives cellular aging when senescent cells remain metabolically active. The senescence associated secretory phenotype can drive development of aging-diseases such as Alzheimer’s disease. Third, neuroinflammation occurs via numerous mechanisms such as microglial activation and is gaining recognition as an etiological factor in the development of Alzheimer’s disease. This review focuses on interactions of alcohol with APOE genotype and aging along these three pathways that may promote Alzheimer’s disease. Further research on these processes may inform development of strategies to prevent onset and progression of Alzheimer’s disease and to delay associated cognitive decline.
Abstract
The world is now well into the third decade of use of effective anti-retroviral therapy (ART) that provides sustained control of HIV-1 viremia (viral loads <200 copies of HIV RNA/microliter). With few exceptions, control of HIV in individual patients is predictable and long lasting. Only a short time ago, the prevailing opinion was that HIV infection ‘physiologically aged’ an individual by ten years or more compared to uninfected subjects and could lead to premature frailty. 1-4 Whereas these findings may have accurately characterized the untreated HIV-infected individual, they do not apply to those on ART. We discuss these concepts and show why they have not held up to scrutiny. Clinical and cellular evidence contradict these statements. Theories about aging in HIV-positive patients arose in the early 2000’s 5 about the time we began to study the course of HIV infection in our clinics, measuring frailty as well as obtaining and preserving blood samples from HIV- and healthy, age-matched control patients allowing us to study cellular aging and immunity as well as the molecular features of HIV genes in viral quasispecies suppressed by ART.
One deleterious outcome of aging may be frailty, once believed to be an ineluctable outcome of aging HIV-infected patients. Most clinicians probably would not argue with a definition of frailty such as, “you’ll know it when you see it.” However useful this definition may be in practice measurable parameters of frailty are needed to conduct a study. We chose to use a phenotypic measurement of frailty, the so-called Fried criteria 6 that are easily and rapidly obtained in the clinic at each visit. 7 The Fried method provides ordinate values for 5 functional aspects of health observed in aging individuals: shrinking weight, slowness, weakness in grip strength, low physical activity and exhaustion. The diagnosis of frailty using these criteria require that any three of such measurements be abnormal. 8 There are many “surrogate measurements of frailty” for HIV patients, the most popular being the “frailty index” wherein one adds up diseases over a lifetime. This information can be obtained from the history and records. However, directly observing our patients in the clinic and measuring for frailty gave us the clue that “frailty” was not permanent, and thus, decline was not inevitable as was held for the uninfected elderly. 9 We found that frailty in HIV patients, with few exceptions, was transient (i.e., reversible), lessened with time clearly related to increasing CD4 cell counts and suppressed viremia due to use of antiretroviral drugs. 10
Darlene E. Berryman
Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701, USA; Edison Biotechnology Institute, Ohio University, Athens, Ohio 45701, USA; Diabetes Institute, Ohio University, Athens, Ohio 45701, USA
Edward O. List
Edison Biotechnology Institute, Ohio University, Athens, Ohio 45701, USA
Grace Lach
Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701, USA; Edison Biotechnology Institute, Ohio University, Athens, Ohio 45701, USA
Jonathan A. Young
Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701, USA; Edison Biotechnology Institute, Ohio University, Athens, Ohio 45701, USA
Zoe A. Kington
Honors Tutorial College, Ohio University, Athens, Ohio 45701, USA
John J. Kopchick
Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701, USA; Edison Biotechnology Institute, Ohio University, Athens, Ohio 45701, USA
Abstract
A reduction in growth hormone has repeatedly been shown to improve healthspan and lifespan in mice and attenuate age-related conditions in subsets of comparable clinical populations. While aging results in progressive physiological changes in many tissues that leads to declines in biological function, this review will focus on the role of growth hormone in adipose tissue with respect to the aging process. Growth hormone dramatically and uniquely alters adipose tissue mass, composition, function and distribution, with decreases in hormone action resulting in a counterintuitive “healthy obese” state. As clinical studies are somewhat limited, much of our understanding of this hormone’s unique effect on adipose tissue and aging comes from mouse lines with specific alterations to the growth hormone axis. Thus, this review will provide an overview of the health span and lifespan consequences of growth hormone action in mouse lines and briefly describe comparable clinical conditions. The review will also summarize the general changes in adipose tissue with normal aging as well as the unique changes in this tissue in response to growth hormones.
Darlene E. Berryman
Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701, USA; Edison Biotechnology Institute, Ohio University, Athens, Ohio 45701, USA; Diabetes Institute, Ohio University, Athens, Ohio 45701, USA
Edward O. List
Edison Biotechnology Institute, Ohio University, Athens, Ohio 45701, USA
Grace Lach
Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701, USA; Edison Biotechnology Institute, Ohio University, Athens, Ohio 45701, USA
Jonathan A. Young
Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701, USA; Edison Biotechnology Institute, Ohio University, Athens, Ohio 45701, USA
Zoe A. Kington
Honors Tutorial College, Ohio University, Athens, Ohio 45701, USA
John J. Kopchick
Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701, USA; Edison Biotechnology Institute, Ohio University, Athens, Ohio 45701, USA
Abstract
A reduction in growth hormone has repeatedly been shown to improve healthspan and lifespan in mice and attenuate age-related conditions in subsets of comparable clinical populations. While aging results in progressive physiological changes in many tissues that leads to declines in biological function, this review will focus on the role of growth hormone in adipose tissue with respect to the aging process. Growth hormone dramatically and uniquely alters adipose tissue mass, composition, function and distribution, with decreases in hormone action resulting in a counterintuitive “healthy obese” state. As clinical studies are somewhat limited, much of our understanding of this hormone’s unique effect on adipose tissue and aging comes from mouse lines with specific alterations to the growth hormone axis. Thus, this review will provide an overview of the healthspan and lifespan consequences of growth hormone action in mouse lines and briefly describe comparable clinical conditions. The review will also summarize the general changes in adipose tissue with normal aging as well as the unique changes in this tissue in response to growth hormone.
Papitchaya Watcharanurak
Faculty of Medical Technology, Prince of Songkla University, Hat Yai, Songkhla, Thailand.
Apiwat Mutirangura
Center of Excellence in Molecular Genetics of Cancer and Human Disease, Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand.
Abstract
Background: Age-associated epigenetic alteration is the underlying cause of DNA damage in aging cells. Two types of youth-associated DNA-protection epigenetic marks, global methylation, and youth-associated genomic stabilization DNA gap (youth-DNA-gap) reduce when cell ages. The epigenomic mark reduction promotes DNA damage and accelerates aging hallmarks. While DNA hypomethylation destabilizes DNA by several mechanisms, the DNA sequence around the youth-DNA-gap is hypermethylated. Therefore, the genomic instability mechanisms underlying DNA hypomethylation and youth-DNA-gap reduction are linked.
Results: DNA gap prevents DNA damage by relieving the torsion forces caused by a twisted wave during DNA strand separation by transcription or replication. When the cells begin to age, hypomethylation and youth-DNA-gap reduction can occur as consequences of the efflux of intranuclear HMGB1. The methylated DNA gaps are formed by several proteins. Box A of HMGB1 possesses a molecular scissor role in producing youth-DNA-gaps. So the lack of a gap-producing role of HMGB1 results in a youth-DNA-gap reduction. The histone deacetylation role of SIRT1, an aging prevention protein, prevents DNA ends of youth-DNA-gaps from being recognized as pathologic DNA breaks. Youth-DNA-gaps are methylated and determined genome distribution by AGO4, an effector protein in RNA-directed DNA methylation. The lack of intranuclear HMGB1 promotes global hypomethylation due to two subsequent mechanisms. First is the loss of AGO4-methylating DNA. The other is the accumulation of DNA damage due to lacking HMGB1-produced DNA gap promoting DNA demethylation while undergoing DNA repair. DNA torsion due to youth-DNA-gap reduction increases DNA damage and, consequently, the DNA damage response (DDR). Persistent DDR promotes cellular senescence. Accumulating senescent cells leads to the deterioration of the structure and function of the human body. Rejuvenating DNA (RED) by adding DNA protection epigenetic marks using genomic stability molecule (GEM) such as box A of HMGB1 increases DNA durability, limits DNA damage, rejuvenates senescence cells, and improves organ structure and function deterioration due to aging.
Conclusion: Reducing youth-associated epigenetic marks is degenerative diseases’ primary molecular pathogenesis mechanism. REDGEM is a new therapeutic strategy inhibiting the upstream molecular aging process that will revolutionize the treatment of DNA damage or age-associated diseases and conditions.
Pegah Derakhshan
Graduate Program in Rehabilitation Sciences, UBC, Vancouver, BC, CA; Centre for Aging Smart Rehabilitation Research Program, GF Strong Rehabilitation, UBC, Vancouver, BC, CA; International Collaboration on Repair Discoveries (ICORD), Vancouver, BC, CA
William C. Miller
Centre for Aging Smart Rehabilitation Research Program, GF Strong Rehabilitation, UBC, Vancouver, BC, CA; International Collaboration on Repair Discoveries (ICORD), Vancouver, BC, CA; Department of Occupational Science & Therapy, UBC, Vancouver, BC, CA
Ethan Simpson
Centre for Aging Smart Rehabilitation Research Program, GF Strong Rehabilitation, UBC, Vancouver, BC, CA; International Collaboration on Repair Discoveries (ICORD), Vancouver, BC, CA; Department of Occupational Science & Therapy, UBC, Vancouver, BC, CA
Christopher B. McBride
Spinal Cord Injury British Columbia, Vancouver, BC, CA
Jaimie Borisoff
International Collaboration on Repair Discoveries (ICORD), Vancouver, BC, CA ; Department of Occupational Science & Therapy, UBC, Vancouver, BC, CA; British Columbia Institute of Technology (BCIT), Burnaby, CA
Julia Schmidt
Centre for Aging Smart Rehabilitation Research Program, GF Strong Rehabilitation, UBC, Vancouver, BC, CA; Department of Occupational Science & Therapy, UBC, Vancouver, BC, CA
W. Ben Mortenson
Centre for Aging Smart Rehabilitation Research Program, GF Strong Rehabilitation, UBC, Vancouver, BC, CA; International Collaboration on Repair Discoveries (ICORD), Vancouver, BC, CA; Department of Occupational Science & Therapy, UBC, Vancouver, BC, CA
Abstract
Introduction: During the COVID-19 pandemic, there was an urgent need for information on dealing with it among people with spinal cord injuries (SCI). Organizations provided resources, but many of them were generic. In some cases, the information was provided by dubious sources, contradictory, or not assessed for usability with individuals with SCI. This study reviewed COVID-19 web-based resources for individuals with SCI and evaluated their quality.
Methods: A scoping review for COVID-19-related web-based resources for individuals with SCI was performed by first identifying SCI-relevant organizations and, subsequently, targeted website searching using a systematic search strategy in May 2021. The included resources were categorized based on their content and format (e.g., video, infographic, text). The resources were evaluated using tools that had been previously validated.
Results: Our search identified 71 SCI organizations and 10,538 potential resources. Based on inclusion and exclusion criteria, 112 resources were included and categorized based on their content into ten main domains: prevention, caregivers, exercise, mental health, stories, telehealth, specific organs/systems, report of evidence, SCI network COVID-19 response and COVID-19 communication rights toolkit. The average score for the quality of the text, infographic, and video resources are 9.72/28 (Range:3-24), 37.75/44 (Range:35-41), and 59.14/80 (Range: 49-75), respectively.
Conclusion: Website resources mainly focused on preventing COVID-19. Only five of them addressed telehealth during COVID-19 for individuals with SCI. The results of this study will inform the development of SCI-oriented toolkits for future pandemics.
Chunhui Yang
Department of Psychiatry, OASIS International Hospital, Beijing, China; Department of Neuropathology, Rush University Medical Center, Rush Alzheimer’s Disease Center, Chicago, USA
Julie A Schneider
Department of Neuropathology, Rush University Medical Center, Rush Alzheimer’s Disease Center, Chicago, USA
Rupal Mehta
Department of Neuropathology, Rush University Medical Center, Rush Alzheimer’s Disease Center, Chicago, USA
Tong Chen
Department of Neurology, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
Zhimin Wei
Department of Pathology, The Affiliated Hospital of Qingdao University, China
Sukriti Nag
Department of Neuropathology, Rush University Medical Center, Rush Alzheimer’s Disease Center, Chicago, USA
Rongwei Huang
Fanglizhihui (Hangzhou) Biotechnology Co. Ltd., China
Abstract
The present report discusses the immune and clearance system of the central nervous system (CNS) in terms of its anatomical, physiological, and biochemical properties. There is now a growing body of evidence that progressive dysfunction of the meningeal lymphatic system should be considered as a risk factor for aging-related brain disorders. In addition, the activity of meningeal lymphatics may alter the access of CSF-carried immune neuromodulators to brain parenchyma, which is also involved in the onset of aging and AD. In the CNS clearance system, impairment of the BBB and small arteries, as well as the major protein of the end feet of astrocytes, AQP4, are associated with aging or AD. The idea of maximizing brain “waste discharge” as a new preventive or therapeutic target for neurodegenerative diseases in the context of healthy aging has been accepted.
Joseph Keenan, MD
Professor Emeritus, University of Minnesota, Department of Family Medicine & Community Health; Associate Professor of Food Science & Nutrition; Director of the University Geriatric Fellowship; Founder and first president of The American Academy of Home Care Medicine.
Abstract
The aging of the global population and the associated increase in chronic disease burden requires a paradigm shift in how we care for older adults, one that could benefit from exploring a return to nicotinic acid (NA) therapy for dyslipidemia management and niacin supplementation to support healthy aging. Despite the exceptional benefits NA demonstrated in the Coronary Drug Project for improving dyslipidemia, reducing cardiovascular disease (CVD), and enhancing longevity, it has since experienced a significant decline in usage. Several factors have contributed to this decline, including poor dosing and side effect management by providers; poor outcomes of subsequent trials that combined NA with statin drugs that, in retrospect, have been attributed to poor study design; and, a faulty meta-analysis that concluded NA did not significantly reduce CVD. In addition, recent research reveals statins increase the risk of dementia in older persons, and providers are urged to look for alternative ways to manage dyslipidemia. One alternative is NA. This review explains the factors that led to the decline in NA use, provides an overview of the lipid and non-lipid effects of niacin (as NA or nicotinamide) for treating dyslipidemia and other age-related diseases, describes clinical protocols that promote efficacy and patient compliance, and identifies other factors that may contribute to a revival of niacin usage, or a “Niacin Rebirth.”
van der Aa H.P.A
van Nassau F
Rozemeijer S.C.A.
Schakel W.
van Rens G.H.M.B.
Amsterdam UMC, location Vrije Universiteit Amsterdam, Ophthalmology, De Boelelaan 1117, Amsterdam, The Netherlands
van Nispen R.M.A.
Amsterdam UMC, location Vrije Universiteit Amsterdam, Ophthalmology, De Boelelaan 1117, Amsterdam, The Netherlands / Amsterdam Public Health, Quality of Care, Mental Health, Aging and Later Life, Amsterdam, The Netherlands
Abstract
Purpose: Mental health problems are common in patients with macular oedema, who receive repeated intravitreal injections with anti-vascular endothelial growth factor. A guided internet-based self-help intervention, called E-PsEYE, was developed to reduce these problems. Patients were referred by their ophthalmologist to follow E-PsEYE individually at home, guided by a social worker from low vision services. Since e-mental health is new in this setting and professionals were collaborating in a novel way, barriers and facilitators during implementation and for future scale-up were evaluated.
Methods: Semi-structured interviews were performed with patients (n=8), ophthalmologists (n=4), heads of ophthalmology departments (n=2), doctor’s assistants (n=3), social workers (n=6) and managers from low vision services (n=2), and representatives from a health insurer (n=2). Data were analyzed using a thematic approach.
Results: Both patients and professionals were satisfied with the potential efficiency and added value of the intervention. They indicated that sufficient digital skills in patients and social workers, information technology (IT) support and adding personalized face-to-face contacts, could facilitate implementation. However, a high workload within the different settings (i.e., hospital and low vision services) and the reluctance of both patients and professionals in focusing on mental health problems could hinder implementation. Moreover, evidence on cost-effectiveness and incorporation in current guidelines were expected to be important for reimbursement and scale-up.
Conclusions: Both on the individual level and in the interaction between stakeholders and their context, different important barriers and facilitators were expressed. To facilitate the use of E-PsEYE in practice, strategies that focus on these aspects could be implemented, e.g. healthcare providers could discuss and normalize mental health complaints and their digital skills could be supported.
Sandra Magalhães
iBiMED: Institute of Biomedicine, Department of Medical Sciences, University of Aveiro, Aveiro, Portugal; CICECO: Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, Aveiro, Portugal
Manuel Teixeira
iBiMED: Institute of Biomedicine, Department of Medical Sciences, University of Aveiro, Aveiro, Portugal
Marisol Gouveia
iBiMED: Institute of Biomedicine, Department of Medical Sciences, University of Aveiro, Aveiro, Portugal
Fernando Ribeiro
iBiMED: Institute of Biomedicine, Department of Medical Sciences, University of Aveiro, Aveiro, Portugal; ESSUA: School of Health Sciences, University of Aveiro, Aveiro, Portugal
Brian J Goodfellow
CICECO: Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, Aveiro, Portugal
Alexandra Nunes
iBiMED: Institute of Biomedicine, Department of Medical Sciences, University of Aveiro, Aveiro, Portugal
Abstract
The loss of proteostasis is a key hallmark of aging and has been well documented using several model systems. However, in biofluids such as blood plasma, little is known about how the loss of proteostasis affects protein conformation during aging.
Our previous work has demonstrated age-related changes in protein conformation in human plasma samples using FTIR spectroscopy and conformation-specific antibodies. To prove the potential of spectroscopy to detect slight changes in protein secondary structure during aging, we have applied the same methodology to a new and independent set of 24 human plasma samples from donors with ages ranging from 40 to 75 years.
The results clearly show that from middle to old age there is a decrease in antiparallel β-sheet structures and an increase in intermolecular β-sheets, indicative of an increase in aggregation-prone proteins in human plasma over time. This confirms the potential of FTIR spectroscopy as a technique to evaluate protein conformational changes related to health and disease and as a suitable method to be used in a clinical setting to produce quick and reliable results.
Challenges and Opportunities in Ageing
Special Issue:
Challenges and Opportunities in Challenges and Opportunities in Ageing
Sunil K. Panchal
School of Pharmacy and Medical Sciences, Griffith University, Gold Coast, QLD 4222, Australia
Lindsay Brown
School of Pharmacy and Medical Sciences, Griffith University, Gold Coast, QLD 4222, Australia
Abstract
Maintaining health during ageing has become a major public health initiative as the proportion of the world’s population aged over 65 years has increased markedly. Macroalgae have been incorporated in the diet for generations, especially in East Asia. Nutritional changes to include macroalgae may provide possibilities for interventions to prevent or reverse the hallmarks of ageing. Their potential to assist in healthy ageing relies on their complex composition including carbohydrates, proteins, minerals, vitamins, fibre and secondary metabolites such as phlorotannins, oxylipins and terpenoids. However, most studies are in animal models with few studies examining the responses in humans to long-term intake. Likely mechanisms of action include reversal of chronic inflammation and gut dysbiosis as part of the changes during ageing. There is now a wide range of foods that incorporate macroalgae, including bread, noodles, yogurt, gluten-free products, and meat and seafood products. Key future priorities with macroalgae include increasing the range of species available for human consumption, defining the health benefits in humans and domestic animals, improving accessibility and decreasing the risk of toxicity from pollutants. Further, health may be improved by indirect effects including wastewater remediation, production of bioenergy and biofertilisers, and decreasing methane production by ruminants. These uses also increase knowledge of macroalgal biology, especially the use ofmolecular engineering techniques to increase sustainable macroalgal biomass production.
Christian Pozzi
University of Applied Sciences and Arts of Southern Switzerland (SUPSI), Centre of Competence on Ageing; PhD Student in Public Health, University of Milano Bicocca – Italy
Andrea Staglianò
San Gerardo dei Tintori IRCCS Foundation, Monza – Italy
Claudia Ballabio
Cooperativa “La Meridiana”, Monza
Chiara De Ponti
Cooperativa “La Meridiana”, Monza
Federica Bartoli
Cooperativa “La Meridiana”, Monza
Laura Antolini
Medical Statistics University of Milano Bicocca – Italy
Maria Cristina Ferrara
PhD Student in Public Health, University of Milano Bicocca – Italy; San Gerardo dei Tintori IRCCS Foundation, Monza – Italy
Alessandro Morandi
Azienda Speciale di Cremona Solidale – Italy; Parc Sanitari Pere Virgili and Vall d’Hebrón Institute of Research, Barcelona – Spain
Stefano Cavalli
University of Applied Sciences and Arts of Southern Switzerland (SUPSI), Centre of Competence on Ageing
Laura N. Gitlin
College of Nursing and Health Professions Drexel University – Philadelphia – USA
Giuseppe Bellelli
San Gerardo dei Tintori IRCCS Foundation, Monza – Italy; School of Medicine and Surgery, University of Milano Bicocca – Italy
Abstract
Background: Nonpharmacological approaches are recommended as first-line treatment for the neuropsychiatric symptoms of persons living with dementia. Tailored Activity Program is a non-pharmacological approach which has shown to reduce neuropsychiatric symptoms and functional dependence of persons living with dementia at the community, as well as caregiver’s distress. The aim of the study is to assess the feasibility of a project in which the Tailored Activity Program is delivered partially at an acute hospital ward and partially at the patient’s home.
Material and Methods: The study is aimed at enrolling 50 dyads (patients/caregivers) from the memory clinic, acute geriatric ward, or short-stay emergency department at the IRCCS San Gerardo dei Tintori, Monza (Italy). Inclusion criteria are: the patient’s clinical diagnosis of dementia, clinically detectable neuropsychiatric symptoms (Neuro Psychiatric Inventory, NPI score >6 in at least one item), the ability to participate in activities of daily living (Katz’s index ≥ 2), the presence of a caregiver (aged ≥ 21 years; minimum 4 hours of daily care), and the willingness of the dyad patient/caregiver to participate in the project. Treatment is delivered both i) in hospital (2 sessions) and ii) at home (6 sessions), including occupational therapy, telemedicine and nursing care provided once a week. The following variables are measured: Neuro Psychiatric Inventory, Time Up and Go Test, Katz’s Index and the level of caregiver’s sense of competence with the Sense of Competence Questionnaire. Data are collected both at baseline, at the end of the treatment, with a follow-up scheduled at 4 months after enrollment. Primary outcome measure is the dyad’s retention rate at 4-month follow-up. Secondary outcomes are the reduction in the patient’s frequency and severity of NPS; the improvement in the patient’s Time Up and Go Test score; the improvement in the patient’s levels of autonomy and participation in activities of daily living and improvement in the caregiver’s Sense of Competence Questionnaire score.
Results and Conclusion: We seek to evaluate whether the Tailored Activity Program is well-received by the patient/caregiver dyad and, consequently, whether our project is feasible. If this objective is achieved, and if we also report some improvement in the secondary outcomes, we can then plan a larger multicenter study aimed at evaluating the effectiveness of this approach, partly delivered at the hospital and partly at patient’s home.
Maria Evandrou
ESRC Centre for Population Change, University of Southampton, Southampton, UK; Centre for Research on Ageing, University of Southampton, Southampton, UK
Jane Falkingham
ESRC Centre for Population Change, University of Southampton, Southampton, UK
Min Qin
ESRC Centre for Population Change, University of Southampton, Southampton, UK
Athina Vlachantoni
ESRC Centre for Population Change, University of Southampton, Southampton, UK; Centre for Research on Ageing, University of Southampton, Southampton, UK
Abstract
Objectives: The COVID-19 crisis significantly reshaped individuals’ daily lives and work, potentially also affecting their mental health. This study examines changes in psychological stress, anxiety, and depression during the first lockdown amongst five British cohorts at different stages of the life course: older adolescence, early adulthood, mid-career, and later life. It investigates the correlation between self-reported stress and life changes across a range of domains including health; education and the move to home schooling; working patterns and furlough; and living arrangements and family life.
Methods: The study analyses data from 14,130 cohort members participating in the special COVID-19 surveys conducted in May 2020. These surveys are part of the ongoing 1946, 1958, 1970, and 2000-01 British birth cohorts, as well as the Next Steps cohort (born in 1989-90). Probit regression models assess the likelihood of increased stress among individuals reporting pandemic-related life changes compared to those who did not, across a range of different life domains. The study also examines the association between heightened stress and subsequent anxiety and depression.
Results: The research highlights the diverse challenges faced by individuals at different life stages during the early phase of the pandemic. Young people faced disrupted education, with many returning to the parental home; parents had to cope with the closure of schools and childcare services, dealing with young children at home; mid-career professionals also found themselves balancing work and family responsibilities; retirees faced cancelled medical appointments and disrupted home care services. All these challenges were associated with significantly increased reported stress among affected individuals; particularly in adolescence and young adulthood, where mental health outcomes were poorer than in older cohorts. Moreover, heightened stress substantially raised the risk of developing anxiety and depression.
Conclusions: The study affirms that individuals in various life stages faced exceptional challenges during the initial lockdown, adversely affecting mental well-being. Adolescents and young adults, experiencing more life changes but lacking coping resources, felt the disruption especially heavily. Going forward, given the potential health consequences of prolonged stress, anxiety, and depression, policymakers must consider these temporary challenges through a life course lens when designing appropriate interventions and support services.
Yurong Zhang
School of Sociology, Beijing Normal University
Yanli Liu
School of Law, Politics and Public Administration, Hebei Normal University
Xiulan Zhang
Emeritus Professor, Beijing Normal University
Abstract
Background: China is facing the challenge of an increasingly ageing population. The proportion of people aged 60 and above increased from 10% to 21.1% between 1999 and 2023 and is projected to reach 28% by 2040. In response to this demographic shift, the Chinese central government has implemented a series of policies that have evolved over time. The rapid advancement of information technology and science has accelerated these changes. However, there is still a research gap in understanding the digital service policies for elderly care.
Methodology: Based on research literature and policy texts, this study specifically focuses on policy development between January 2019 and January 2024. Seventy traceable national policy texts were categorized and analyzed, gathered from the State Council’s policy document database and the official websites of national ministries.
Result: The 70 policies were interpreted and categorized into three major aspects. Firstly, the policies on the improvement of traditional elderly care aimed to meet diverse needs by focusing on health and medical care, the management and standards of serving institutions, service improvements and standardization, and the development of the service workforce. Secondly, the policies on system integration between elderly care and other industries included the integration of finance and elderly care, the construction of the insurance system, long-term care institutions and insurance, hospice care, and the silver economy. Thirdly, the policies on digital services comprised the smart healthcare industry, information accessibility, elderly-friendly digital technology and empowerment, and the creation of elderly-friendly communities and societies.
Conclusion: The development concepts and contents of China’s elderly care policy have evolved. The acceleration of transformation and promotion of the silver economy has become a new comprehensive and universal measure. Despite recent policy developments indicating a growing trend towards integration, there remains considerable room for improvement in actual implementation. This should focus on the uneven development of the “three pillars” of the pension system, insufficient innovation in financial products, and inadequate industry financing channels. It is important to be alert to the persistent problems and obstacles, which widen the gap in elderly welfare, create new forms of social inequality and exclusion, and hinder the development of a friendly information society.
Abstract
The organisation of society into social systems led, from the nineteenth century onwards, to the differentiation of medicine. Its object has been diseases, with the sub-systems of healthcare, responsible for diagnosis and treatment, and public health, responsible for communicating the truths of medical science to the population with the aim of preventing and treating diseases. This organisation, which remains effective, is currently facing two problems:
- Its possible extension of its scope to include health as understood by international organisations, in order to meet the challenges posed by the rapid transformation of the planet: global warming, overpopulation, ageing, poverty, etc.
- The ability to make this advice effective at a time when there is no longer an entity that can generate the confidence needed to apply its recommendations.
To overcome the silos that have prevented the changes we are undergoing today, it will be necessary to organise collaborations that the revolution brought about by Artificial Intelligence (AI) may be able to facilitate.
Abstract
Introduction: Chronic Obstructive Pulmonary Disease (COPD) in exacerbation is globally a frequent cause of admission. In Denmark, annual national epidemiological data on COPD patients have been reported since 2008, and there has been registered a reduction in admissions due to COPD in exacerbation of approximately 25% compared to 2014. There has also been revealed regional differences in use of non-invasive ventilation (NIV) and mortality, and especially, the 30-day mortality rate was significantly higher at Odense University Hospital compared to the other regions in 2022, where the number of admissions was even lower due to the effect of the COVID- 19 pandemic. We therefore decided to repeat an internal audit of all admissions with COPD exacerbation with focus on in-house initiation of NIV as an add-on treatment to standard treatment and mortality.
Methods: Patient data was collected from medical records from the COPD cohort, and the cohort was defined by discharge between 1 st of January to 31 st of December 2023, admission at Odense University Hospital, and confirmed COPD exacerbation.
Results: The COPD cohort comprised in all 396 patients. NIV criteria were fulfilled in 112 patients and initiation of NIV in 92.9%. The 30-day mortality rate was in this cohort 16.2%. Patients who died within 30 days, were significantly older than patients still alive, although there was no difference in comorbidities. The patients, who received NIV and died, had significantly fewer comorbidites compared to patients who died and did not receive NIV.
Conclusions: Acute treatment was given according to guidelines, and the need of NIV was found in 28% of the patients in the cohort. The patients that died were significantly older compared to survivors. The increased mortality can therefore be a consequence of admissions with an ageing population, and, hence, more fragile COPD patients. The COPD population in Denmark is getting older, although there are still some patients with severe COPD dying at younger age.
Lisa Brandon
St James Hospital, Dublin, Ireland
Niall Connolly
St James Hospital, Dublin, Ireland
Mark Hensey
St James Hospital, Dublin, Ireland
Stephen O’Connor
St James Hospital, Dublin, Ireland
I Cruz-Gonzalez
University of Salamanca, Spain
Rose Anne Kenny
St James Hospital, Dublin, Ireland; Trinity College, Dublin, Ireland
Andrew O Maree
St James Hospital, Dublin, Ireland; Trinity College, Dublin, Ireland
Abstract
Aortic stenosis remains the most common valvular abnormality that requires intervention and is becoming more prevalent with an ageing population. Untreated symptomatic severe aortic stenosis is associated with a mortality of 50-60% within two years. Valve replacement either surgical or transcatheter remains the only effective treatment.
The autonomic nervous system involuntarily controls many basic cardiac, respiratory, gastrointestinal and genitourinary functions and plays a central role in the regulation of heart rate and blood pressure. Cardiovascular autonomic dysfunction has shown to be a marker of increased mortality. We discuss current methods to assess autonomic function, alongside abnormalities noted in common cardiac conditions and their correlation to mortality, and review current literature available that confirms severe aortic stenosis is associated with dysregulation of cardiovascular autonomic system.
Challenges and Opportunities in Oxidative Stress
Special Issue:
Challenges and Opportunities in Oxidative Stress
Marina Lancaster D. de Moraes Salles
Department of Biochemistry and Nutrition, School of Nutrition, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília, São Paulo 17525-902, Brazil
Nataly Garcia
Department of Biochemistry and Nutrition, School of Nutrition, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília, São Paulo 17525-902, Brazil
Lucas Fornari Laurindo
Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília, São Paulo 17525-902, Brazil
Angiseli Damaceno Scanavacca
Department of Biochemistry and Nutrition, School of Nutrition, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília, São Paulo 17525-902, Brazil
Karla Regina Ezídio
Department of Biochemistry and Nutrition, School of Nutrition, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília, São Paulo 17525-902, Brazil
Ricardo José Tofano
Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília, São Paulo 17525-902, Brazil
Cláudia Rucco Penteado Detregiachi
Department of Biochemistry and Nutrition, School of Nutrition, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília, São Paulo 17525-902, Brazil; Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília, São Paulo 17525-902, Brazil
Jesselina F. dos Santos Haber
Department of Biochemistry and Nutrition, School of Nutrition, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília, São Paulo 17525-902, Brazil
Mara Silva Foratto Marconatto
Department of Biochemistry and Nutrition, School of Nutrition, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília, São Paulo 17525-902, Brazil
Sandra Maria Barbalho
Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília, São Paulo 17525-902, Brazil; Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília, São Paulo 17525-902, Brazil; Department of Biochemistry, School of Food and Technology of Marilia (FATEC), Avenida Castro Alves, 62, Marília, São Paulo 17500-000, Brazil
Karina Quesada
Department of Biochemistry and Nutrition, School of Nutrition, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília, São Paulo 17525-902, Brazil; Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília, São Paulo 17525-902, Brazil
Abstract
Poor sleep quality can affect cardiovascular health and is considered a significant risk factor for the development of risk factors for Metabolic syndrome (MetS). This study aimed to investigate possible associations between sleep quality measured by the Pittsburgh Sleep Quality Index and the MetS. This was a cross-sectional that comprised data from 208 patients. Biochemical and anthropometric parameters were assessed. The identification of MetS was performed according to the International Diabetes Federation guidelines. The quantitative variables were described with the support of the BioEstat 5.3 software. To assess the association of the studied variables with the diagnosis of MetS, the Mann-Whitney and Chi-square (n x n) statistical tests were used. The level of significance considered was 5%. According to the International Diabetes Federation criteria, 111 (53,36%) men and women presented MetS. There were no statically significant differences between the groups with or without sleep disorders and the values of waist circumference (p=0.6996), high-density lipoprotein cholesterol levels (p=0.7940), triglycerides levels (p=0.8703), blood pressure values (p= 0.9851, and p=0.9795 for systolic and diastolic blood pressure, respectively), and glycemia (p=0.5351). Eighty-eight volunteers (42%) presented sleep quality dysfunction, with the highest proportion observed among individuals affected by MetS (p=0.0019). Our results indicate an association between sleep quality and the prevalence of MetS . Therefore, sleep quality could be evaluated in patients with MetS so that the therapeutic strategy would not be limited to the intervention in biochemical and anthropometric factors.
Angelo Azzi
Tufts University, Boston, MA, USA, School of Graduate Biomedical Pharmacology and Drug Development Program
Abstract
Oxidative stress refers to an imbalance between the production of reactive oxygen species and the ability of the body to detoxify or repair the resulting damage. However, it will be shown that the term “oxidative stress” is often used instead of the correct “oxidative damage”. The term “eustress” has been used for describing beneficial signaling by small amounts of reactive oxygen species, but it will be shown that reactive oxygen species signaling can also promote cancer cell growth. The term “oxidative distress” has been created to describe the negative effects produced on cells, organs, and the entire body by large amounts of reactive oxygen species. However, if the reactive oxygen species are used to kill infectious microorganisms, the result is beneficial. Measurements of oxidative stress in body fluids or tissue specimens are a measure of oxidative damage potentially occurring simultaneously in different cells, tissues, and organs; they only provide a sum of non-separable events, possibly with opposite effects. There is no officially approved therapy to prevent or treat oxidative stress or oxidative damage. This implies that while oxidative stress issues are already a complex challenge for basic biological sciences, in a clinical setting oxidative stress is only a term of convenience with no diagnostic or therapeutic value. A critical appraisal of oxidative stress terminology, quantification, and therapeutic attempts is presented.
Luis-Eder Vargas-Campos
Maestro en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Marco-A. Adams-Reyes
Acapulco de Juárez Guerrero, México. 2 Especialista en Implantología Facultad Centro Oeste Paulista FACOP, Bauru Sao Paulo Brasil.
Julio-Cesar Adams-Ocampo
Maestría en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Juan-Manuel Luna-Gomez
Especialista en Ortodoncia; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Yanet Medina-Rojas
Maestra en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Luis-Martin Vargas-Zuñiga
Doctor en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Abstract
Introduction. – In this review, one of the mechanisms that is generated in inflammation, oxidative stress, was analyzed. Inflammation is an immune system response, it is essential for survival and recovery, but it can cause damage to the body, due to oxidative stress that occurs when there is an imbalance between the production of reactive oxygen species and the body’s ability to neutralize them with Endogenous antioxidants contribute to the development of chronic diseases such as cardiovascular, diabetes, autoimmune diseases, cancer, neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s, amyotrophic lateral sclerosis.
Aim. – Evaluate the literature about inflammation from the basic to the clinical level.
Methodology. – Databases such as MEDLINE/PubMed and ScienceDirect regarding Inflammation were analyzed.
Results. – Despite recent advances in the understanding of inflammation and oxidative stress, there are still important challenges in the study and treatment of these conditions, on the one hand, it is necessary to develop more precise biomarkers to evaluate oxidative stress and inflammation in patients. On the other hand, new therapeutic approaches are needed to modulate inflammation and oxidative stress more effectively and specifically.
Conclusion. – That the study of inflammation and oxidative stress is crucial to understanding the pathophysiological bases of various chronic diseases and that advances in the field of inflammation and oxidative stress have provided new therapeutic perspectives for the treatment and prevention of chronic diseases.
Luis-Eder Vargas-Campos
Maestro en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Marco-A. Adams-Reyes
Acapulco de Juárez Guerrero, México. 2 Especialista en Implantología Facultad Centro Oeste Paulista FACOP, Bauru Sao Paulo Brasil.
Julio-Cesar Adams-Ocampo
Maestría en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Juan-Manuel Luna-Gomez
Especialista en Ortodoncia; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Yanet Medina-Rojas
Maestra en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Luis-Martin Vargas-Zuñiga
Doctor en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Abstract
Introduction. – In this review, one of the mechanisms that is generated in inflammation, oxidative stress, was analyzed. Inflammation is an immune system response, it is essential for survival and recovery, but it can cause damage to the body, due to oxidative stress that occurs when there is an imbalance between the production of reactive oxygen species and the body’s ability to neutralize them with Endogenous antioxidants contribute to the development of chronic diseases such as cardiovascular, diabetes, autoimmune diseases, cancer, neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s, amyotrophic lateral sclerosis.
Aim. – Evaluate the literature about inflammation from the basic to the clinical level.
Methodology. – Databases such as MEDLINE/PubMed and ScienceDirect regarding Inflammation were analyzed.
Results. – Despite recent advances in the understanding of inflammation and oxidative stress, there are still important challenges in the study and treatment of these conditions, on the one hand, it is necessary to develop more precise biomarkers to evaluate oxidative stress and inflammation in patients. On the other hand, new therapeutic approaches are needed to modulate inflammation and oxidative stress more effectively and specifically.
Conclusion. – That the study of inflammation and oxidative stress is crucial to understanding the pathophysiological bases of various chronic diseases and that advances in the field of inflammation and oxidative stress have provided new therapeutic perspectives for the treatment and prevention of chronic diseases.
Vincent Dartigue
Division of Animal and Nutritional Science, West Virginia University, Morgantown, WV
Knox Van Dyke
Department of Biochemistry, West Virginia University School of Medicine, Morgantown, WV
Hillar Klandorf
Division of Animal and Nutritional Science, West Virginia University, Morgantown, WV
Kimberly M. Barnes
Division of Animal and Nutritional Science, West Virginia University, Morgantown, WV
Abstract
Selection for rapid growth in poultry can be linked to an exaggerated state of oxidative stress (reactive oxidative species). Reactive oxidative species are kept in balance by endogenous and exogenous antioxidants. Two compounds, conjugated linoleic acid (CLA) and berberine a purified compound from plant root extract have been suggested to ameliorate oxidative stress. A six-week study examined the effect of CLA and berberine supplementation on markers of oxidative-stress in poultry. Day old broiler chickens (n=60) were equally divided into six groups; a control, a CLA group where half of the regular oil used in a standard was substituted for a CLA oil mixture, a berberine group consisting of berberine supplementation, an allopurinol group, a CLA and allopurinol with the same dose as the CLA and allopurinol groups and a berberine and allopurinol group. The allopurinol was added to induce an oxidative stress state. Body weight, plasma uric acid, plasma glucose, and relative gene expression of six endogenous liver antioxidants were measured during the course of the study. The addition of allopurinol to the diet induced an oxidative stress state as measured by a significant reduction in plasma uric acid. There were no significant changes in BW and blood glucose concentrations. There was a 10-fold increase in the relative mRNA expression of superoxide dismutase 2 and 3 as well as glutathione peroxidase 1 and 3 in CLA+ALLO and BRB+ALLO treatment groups. Notably, CLA increased the expression of uncoupling protein 19-fold compared to control, while the addition of allopurinol blocked these changes. In contrast, there was a slight increase in the uncoupling protein in the BRB+ALLO treatment. Despite the increase in mRNA expression of the antioxidants genes, these results suggest that at the dosages administered, CLA and berberine were not effective in reversing the oxidative stress induced by allopurinol.
Luis-Eder Vargas-Campos
Maestro en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Marco-A. Adams-Reyes
Acapulco de Juárez Guerrero, México. 2 Especialista en Implantología Facultad Centro Oeste Paulista FACOP, Bauru Sao Paulo Brasil.
Julio-Cesar Adams-Ocampo
Maestría en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Juan-Manuel Luna-Gomez
Especialista en Ortodoncia; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Yanet Medina-Rojas
Maestra en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Luis-Martin Vargas-Zuñiga
Doctor en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Abstract
Introduction. – In this review, one of the mechanisms that is generated in inflammation, oxidative stress, was analyzed. Inflammation is an immune system response, it is essential for survival and recovery, but it can cause damage to the body, due to oxidative stress that occurs when there is an imbalance between the production of reactive oxygen species and the body’s ability to neutralize them with Endogenous antioxidants contribute to the development of chronic diseases such as cardiovascular, diabetes, autoimmune diseases, cancer, neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s, amyotrophic lateral sclerosis.
Aim. – Evaluate the literature about inflammation from the basic to the clinical level.
Methodology. – Databases such as MEDLINE/PubMed and ScienceDirect regarding Inflammation were analyzed.
Results. – Despite recent advances in the understanding of inflammation and oxidative stress, there are still important challenges in the study and treatment of these conditions, on the one hand, it is necessary to develop more precise biomarkers to evaluate oxidative stress and inflammation in patients. On the other hand, new therapeutic approaches are needed to modulate inflammation and oxidative stress more effectively and specifically.
Conclusion. – That the study of inflammation and oxidative stress is crucial to understanding the pathophysiological bases of various chronic diseases and that advances in the field of inflammation and oxidative stress have provided new therapeutic perspectives for the treatment and prevention of chronic diseases.
Vincent Dartigue
Division of Animal and Nutritional Science, West Virginia University, Morgantown, WV
Knox Van Dyke
Department of Biochemistry, West Virginia University School of Medicine, Morgantown, WV
Hillar Klandorf
Division of Animal and Nutritional Science, West Virginia University, Morgantown, WV
Kimberly M. Barnes
Division of Animal and Nutritional Science, West Virginia University, Morgantown, WV
Abstract
Selection for rapid growth in poultry can be linked to an exaggerated state of oxidative stress (reactive oxidative species). Reactive oxidative species are kept in balance by endogenous and exogenous antioxidants. Two compounds, conjugated linoleic acid (CLA) and berberine a purified compound from plant root extract have been suggested to ameliorate oxidative stress. A six-week study examined the effect of CLA and berberine supplementation on markers of oxidative-stress in poultry. Day old broiler chickens (n=60) were equally divided into six groups; a control, a CLA group where half of the regular oil used in a standard was substituted for a CLA oil mixture, a berberine group consisting of berberine supplementation, an allopurinol group, a CLA and allopurinol with the same dose as the CLA and allopurinol groups and a berberine and allopurinol group. The allopurinol was added to induce an oxidative stress state. Body weight, plasma uric acid, plasma glucose, and relative gene expression of six endogenous liver antioxidants were measured during the course of the study. The addition of allopurinol to the diet induced an oxidative stress state as measured by a significant reduction in plasma uric acid. There were no significant changes in BW and blood glucose concentrations. There was a 10-fold increase in the relative mRNA expression of superoxide dismutase 2 and 3 as well as glutathione peroxidase 1 and 3 in CLA+ALLO and BRB+ALLO treatment groups. Notably, CLA increased the expression of uncoupling protein 19-fold compared to control, while the addition of allopurinol blocked these changes. In contrast, there was a slight increase in the uncoupling protein in the BRB+ALLO treatment. Despite the increase in mRNA expression of the antioxidants genes, these results suggest that at the dosages administered, CLA and berberine were not effective in reversing the oxidative stress induced by allopurinol.
Luis-Eder Vargas-Campos
Maestro en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Marco-A. Adams-Reyes
Acapulco de Juárez Guerrero, México. 2 Especialista en Implantología Facultad Centro Oeste Paulista FACOP, Bauru Sao Paulo Brasil.
Julio-Cesar Adams-Ocampo
Maestría en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Juan-Manuel Luna-Gomez
Especialista en Ortodoncia; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Yanet Medina-Rojas
Maestra en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Luis-Martin Vargas-Zuñiga
Doctor en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Abstract
Introduction. – In this review, one of the mechanisms that is generated in inflammation, oxidative stress, was analyzed. Inflammation is an immune system response, it is essential for survival and recovery, but it can cause damage to the body, due to oxidative stress that occurs when there is an imbalance between the production of reactive oxygen species and the body’s ability to neutralize them with Endogenous antioxidants contribute to the development of chronic diseases such as cardiovascular, diabetes, autoimmune diseases, cancer, neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s, amyotrophic lateral sclerosis.
Aim. – Evaluate the literature about inflammation from the basic to the clinical level.
Methodology. – Databases such as MEDLINE/PubMed and ScienceDirect regarding Inflammation were analyzed.
Results. – Despite recent advances in the understanding of inflammation and oxidative stress, there are still important challenges in the study and treatment of these conditions, on the one hand, it is necessary to develop more precise biomarkers to evaluate oxidative stress and inflammation in patients. On the other hand, new therapeutic approaches are needed to modulate inflammation and oxidative stress more effectively and specifically.
Conclusion. – That the study of inflammation and oxidative stress is crucial to understanding the pathophysiological bases of various chronic diseases and that advances in the field of inflammation and oxidative stress have provided new therapeutic perspectives for the treatment and prevention of chronic diseases.
Vincent Dartigue
Division of Animal and Nutritional Science, West Virginia University, Morgantown, WV
Knox Van Dyke
Department of Biochemistry, West Virginia University School of Medicine, Morgantown, WV
Hillar Klandorf
Division of Animal and Nutritional Science, West Virginia University, Morgantown, WV
Kimberly M. Barnes
Division of Animal and Nutritional Science, West Virginia University, Morgantown, WV
Abstract
Selection for rapid growth in poultry can be linked to an exaggerated state of oxidative stress (reactive oxidative species). Reactive oxidative species are kept in balance by endogenous and exogenous antioxidants. Two compounds, conjugated linoleic acid (CLA) and berberine a purified compound from plant root extract have been suggested to ameliorate oxidative stress. A six-week study examined the effect of CLA and berberine supplementation on markers of oxidative-stress in poultry. Day old broiler chickens (n=60) were equally divided into six groups; a control, a CLA group where half of the regular oil used in a standard was substituted for a CLA oil mixture, a berberine group consisting of berberine supplementation, an allopurinol group, a CLA and allopurinol with the same dose as the CLA and allopurinol groups and a berberine and allopurinol group. The allopurinol was added to induce an oxidative stress state. Body weight, plasma uric acid, plasma glucose, and relative gene expression of six endogenous liver antioxidants were measured during the course of the study. The addition of allopurinol to the diet induced an oxidative stress state as measured by a significant reduction in plasma uric acid. There were no significant changes in BW and blood glucose concentrations. There was a 10-fold increase in the relative mRNA expression of superoxide dismutase 2 and 3 as well as glutathione peroxidase 1 and 3 in CLA+ALLO and BRB+ALLO treatment groups. Notably, CLA increased the expression of uncoupling protein 19-fold compared to control, while the addition of allopurinol blocked these changes. In contrast, there was a slight increase in the uncoupling protein in the BRB+ALLO treatment. Despite the increase in mRNA expression of the antioxidants genes, these results suggest that at the dosages administered, CLA and berberine were not effective in reversing the oxidative stress induced by allopurinol.
Luis-Eder Vargas-Campos
Maestro en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Marco-A. Adams-Reyes
Acapulco de Juárez Guerrero, México. 2 Especialista en Implantología Facultad Centro Oeste Paulista FACOP, Bauru Sao Paulo Brasil.
Julio-Cesar Adams-Ocampo
Maestría en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Juan-Manuel Luna-Gomez
Especialista en Ortodoncia; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Yanet Medina-Rojas
Maestra en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Luis-Martin Vargas-Zuñiga
Doctor en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Abstract
Introduction. – In this review, one of the mechanisms that is generated in inflammation, oxidative stress, was analyzed. Inflammation is an immune system response, it is essential for survival and recovery, but it can cause damage to the body, due to oxidative stress that occurs when there is an imbalance between the production of reactive oxygen species and the body’s ability to neutralize them with Endogenous antioxidants contribute to the development of chronic diseases such as cardiovascular, diabetes, autoimmune diseases, cancer, neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s, amyotrophic lateral sclerosis.
Aim. – Evaluate the literature about inflammation from the basic to the clinical level.
Methodology. – Databases such as MEDLINE/PubMed and ScienceDirect regarding Inflammation were analyzed.
Results. – Despite recent advances in the understanding of inflammation and oxidative stress, there are still important challenges in the study and treatment of these conditions, on the one hand, it is necessary to develop more precise biomarkers to evaluate oxidative stress and inflammation in patients. On the other hand, new therapeutic approaches are needed to modulate inflammation and oxidative stress more effectively and specifically.
Conclusion. – That the study of inflammation and oxidative stress is crucial to understanding the pathophysiological bases of various chronic diseases and that advances in the field of inflammation and oxidative stress have provided new therapeutic perspectives for the treatment and prevention of chronic diseases.
Vincent Dartigue
Division of Animal and Nutritional Science, West Virginia University, Morgantown, WV
Knox Van Dyke
Department of Biochemistry, West Virginia University School of Medicine, Morgantown, WV
Hillar Klandorf
Division of Animal and Nutritional Science, West Virginia University, Morgantown, WV
Kimberly M. Barnes
Division of Animal and Nutritional Science, West Virginia University, Morgantown, WV
Abstract
Selection for rapid growth in poultry can be linked to an exaggerated state of oxidative stress (reactive oxidative species). Reactive oxidative species are kept in balance by endogenous and exogenous antioxidants. Two compounds, conjugated linoleic acid (CLA) and berberine a purified compound from plant root extract have been suggested to ameliorate oxidative stress. A six-week study examined the effect of CLA and berberine supplementation on markers of oxidative-stress in poultry. Day old broiler chickens (n=60) were equally divided into six groups; a control, a CLA group where half of the regular oil used in a standard was substituted for a CLA oil mixture, a berberine group consisting of berberine supplementation, an allopurinol group, a CLA and allopurinol with the same dose as the CLA and allopurinol groups and a berberine and allopurinol group. The allopurinol was added to induce an oxidative stress state. Body weight, plasma uric acid, plasma glucose, and relative gene expression of six endogenous liver antioxidants were measured during the course of the study. The addition of allopurinol to the diet induced an oxidative stress state as measured by a significant reduction in plasma uric acid. There were no significant changes in BW and blood glucose concentrations. There was a 10-fold increase in the relative mRNA expression of superoxide dismutase 2 and 3 as well as glutathione peroxidase 1 and 3 in CLA+ALLO and BRB+ALLO treatment groups. Notably, CLA increased the expression of uncoupling protein 19-fold compared to control, while the addition of allopurinol blocked these changes. In contrast, there was a slight increase in the uncoupling protein in the BRB+ALLO treatment. Despite the increase in mRNA expression of the antioxidants genes, these results suggest that at the dosages administered, CLA and berberine were not effective in reversing the oxidative stress induced by allopurinol.
Luis-Eder Vargas-Campos
Maestro en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Marco-A. Adams-Reyes
Acapulco de Juárez Guerrero, México. 2 Especialista en Implantología Facultad Centro Oeste Paulista FACOP, Bauru Sao Paulo Brasil.
Julio-Cesar Adams-Ocampo
Maestría en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Juan-Manuel Luna-Gomez
Especialista en Ortodoncia; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Yanet Medina-Rojas
Maestra en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Luis-Martin Vargas-Zuñiga
Doctor en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Abstract
Introduction. – In this review, one of the mechanisms that is generated in inflammation, oxidative stress, was analyzed. Inflammation is an immune system response, it is essential for survival and recovery, but it can cause damage to the body, due to oxidative stress that occurs when there is an imbalance between the production of reactive oxygen species and the body’s ability to neutralize them with Endogenous antioxidants contribute to the development of chronic diseases such as cardiovascular, diabetes, autoimmune diseases, cancer, neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s, amyotrophic lateral sclerosis.
Aim. – Evaluate the literature about inflammation from the basic to the clinical level.
Methodology. – Databases such as MEDLINE/PubMed and ScienceDirect regarding Inflammation were analyzed.
Results. – Despite recent advances in the understanding of inflammation and oxidative stress, there are still important challenges in the study and treatment of these conditions, on the one hand, it is necessary to develop more precise biomarkers to evaluate oxidative stress and inflammation in patients. On the other hand, new therapeutic approaches are needed to modulate inflammation and oxidative stress more effectively and specifically.
Conclusion. – That the study of inflammation and oxidative stress is crucial to understanding the pathophysiological bases of various chronic diseases and that advances in the field of inflammation and oxidative stress have provided new therapeutic perspectives for the treatment and prevention of chronic diseases.
Vincent Dartigue
Division of Animal and Nutritional Science, West Virginia University, Morgantown, WV
Knox Van Dyke
Department of Biochemistry, West Virginia University School of Medicine, Morgantown, WV
Hillar Klandorf
Division of Animal and Nutritional Science, West Virginia University, Morgantown, WV
Kimberly M. Barnes
Division of Animal and Nutritional Science, West Virginia University, Morgantown, WV
Abstract
Selection for rapid growth in poultry can be linked to an exaggerated state of oxidative stress (reactive oxidative species). Reactive oxidative species are kept in balance by endogenous and exogenous antioxidants. Two compounds, conjugated linoleic acid (CLA) and berberine a purified compound from plant root extract have been suggested to ameliorate oxidative stress. A six-week study examined the effect of CLA and berberine supplementation on markers of oxidative-stress in poultry. Day old broiler chickens (n=60) were equally divided into six groups; a control, a CLA group where half of the regular oil used in a standard was substituted for a CLA oil mixture, a berberine group consisting of berberine supplementation, an allopurinol group, a CLA and allopurinol with the same dose as the CLA and allopurinol groups and a berberine and allopurinol group. The allopurinol was added to induce an oxidative stress state. Body weight, plasma uric acid, plasma glucose, and relative gene expression of six endogenous liver antioxidants were measured during the course of the study. The addition of allopurinol to the diet induced an oxidative stress state as measured by a significant reduction in plasma uric acid. There were no significant changes in BW and blood glucose concentrations. There was a 10-fold increase in the relative mRNA expression of superoxide dismutase 2 and 3 as well as glutathione peroxidase 1 and 3 in CLA+ALLO and BRB+ALLO treatment groups. Notably, CLA increased the expression of uncoupling protein 19-fold compared to control, while the addition of allopurinol blocked these changes. In contrast, there was a slight increase in the uncoupling protein in the BRB+ALLO treatment. Despite the increase in mRNA expression of the antioxidants genes, these results suggest that at the dosages administered, CLA and berberine were not effective in reversing the oxidative stress induced by allopurinol.
Luis-Eder Vargas-Campos
Maestro en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Marco-A. Adams-Reyes
Acapulco de Juárez Guerrero, México. 2 Especialista en Implantología Facultad Centro Oeste Paulista FACOP, Bauru Sao Paulo Brasil.
Julio-Cesar Adams-Ocampo
Maestría en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Juan-Manuel Luna-Gomez
Especialista en Ortodoncia; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Yanet Medina-Rojas
Maestra en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Luis-Martin Vargas-Zuñiga
Doctor en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Abstract
Introduction. – In this review, one of the mechanisms that is generated in inflammation, oxidative stress, was analyzed. Inflammation is an immune system response, it is essential for survival and recovery, but it can cause damage to the body, due to oxidative stress that occurs when there is an imbalance between the production of reactive oxygen species and the body’s ability to neutralize them with Endogenous antioxidants contribute to the development of chronic diseases such as cardiovascular, diabetes, autoimmune diseases, cancer, neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s, amyotrophic lateral sclerosis.
Aim. – Evaluate the literature about inflammation from the basic to the clinical level.
Methodology. – Databases such as MEDLINE/PubMed and ScienceDirect regarding Inflammation were analyzed.
Results. – Despite recent advances in the understanding of inflammation and oxidative stress, there are still important challenges in the study and treatment of these conditions, on the one hand, it is necessary to develop more precise biomarkers to evaluate oxidative stress and inflammation in patients. On the other hand, new therapeutic approaches are needed to modulate inflammation and oxidative stress more effectively and specifically.
Conclusion. – That the study of inflammation and oxidative stress is crucial to understanding the pathophysiological bases of various chronic diseases and that advances in the field of inflammation and oxidative stress have provided new therapeutic perspectives for the treatment and prevention of chronic diseases.
Vincent Dartigue
Division of Animal and Nutritional Science, West Virginia University, Morgantown, WV
Knox Van Dyke
Department of Biochemistry, West Virginia University School of Medicine, Morgantown, WV
Hillar Klandorf
Division of Animal and Nutritional Science, West Virginia University, Morgantown, WV
Kimberly M. Barnes
Division of Animal and Nutritional Science, West Virginia University, Morgantown, WV
Abstract
Selection for rapid growth in poultry can be linked to an exaggerated state of oxidative stress (reactive oxidative species). Reactive oxidative species are kept in balance by endogenous and exogenous antioxidants. Two compounds, conjugated linoleic acid (CLA) and berberine a purified compound from plant root extract have been suggested to ameliorate oxidative stress. A six-week study examined the effect of CLA and berberine supplementation on markers of oxidative-stress in poultry. Day old broiler chickens (n=60) were equally divided into six groups; a control, a CLA group where half of the regular oil used in a standard was substituted for a CLA oil mixture, a berberine group consisting of berberine supplementation, an allopurinol group, a CLA and allopurinol with the same dose as the CLA and allopurinol groups and a berberine and allopurinol group. The allopurinol was added to induce an oxidative stress state. Body weight, plasma uric acid, plasma glucose, and relative gene expression of six endogenous liver antioxidants were measured during the course of the study. The addition of allopurinol to the diet induced an oxidative stress state as measured by a significant reduction in plasma uric acid. There were no significant changes in BW and blood glucose concentrations. There was a 10-fold increase in the relative mRNA expression of superoxide dismutase 2 and 3 as well as glutathione peroxidase 1 and 3 in CLA+ALLO and BRB+ALLO treatment groups. Notably, CLA increased the expression of uncoupling protein 19-fold compared to control, while the addition of allopurinol blocked these changes. In contrast, there was a slight increase in the uncoupling protein in the BRB+ALLO treatment. Despite the increase in mRNA expression of the antioxidants genes, these results suggest that at the dosages administered, CLA and berberine were not effective in reversing the oxidative stress induced by allopurinol.
Luis-Eder Vargas-Campos
Maestro en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Marco-A. Adams-Reyes
Acapulco de Juárez Guerrero, México. 2 Especialista en Implantología Facultad Centro Oeste Paulista FACOP, Bauru Sao Paulo Brasil.
Julio-Cesar Adams-Ocampo
Maestría en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Juan-Manuel Luna-Gomez
Especialista en Ortodoncia; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Yanet Medina-Rojas
Maestra en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Luis-Martin Vargas-Zuñiga
Doctor en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Abstract
Introduction. – In this review, one of the mechanisms that is generated in inflammation, oxidative stress, was analyzed. Inflammation is an immune system response, it is essential for survival and recovery, but it can cause damage to the body, due to oxidative stress that occurs when there is an imbalance between the production of reactive oxygen species and the body’s ability to neutralize them with Endogenous antioxidants contribute to the development of chronic diseases such as cardiovascular, diabetes, autoimmune diseases, cancer, neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s, amyotrophic lateral sclerosis.
Aim. – Evaluate the literature about inflammation from the basic to the clinical level.
Methodology. – Databases such as MEDLINE/PubMed and ScienceDirect regarding Inflammation were analyzed.
Results. – Despite recent advances in the understanding of inflammation and oxidative stress, there are still important challenges in the study and treatment of these conditions, on the one hand, it is necessary to develop more precise biomarkers to evaluate oxidative stress and inflammation in patients. On the other hand, new therapeutic approaches are needed to modulate inflammation and oxidative stress more effectively and specifically.
Conclusion. – That the study of inflammation and oxidative stress is crucial to understanding the pathophysiological bases of various chronic diseases and that advances in the field of inflammation and oxidative stress have provided new therapeutic perspectives for the treatment and prevention of chronic diseases.
Vincent Dartigue
Division of Animal and Nutritional Science, West Virginia University, Morgantown, WV
Knox Van Dyke
Department of Biochemistry, West Virginia University School of Medicine, Morgantown, WV
Hillar Klandorf
Division of Animal and Nutritional Science, West Virginia University, Morgantown, WV
Kimberly M. Barnes
Division of Animal and Nutritional Science, West Virginia University, Morgantown, WV
Abstract
Selection for rapid growth in poultry can be linked to an exaggerated state of oxidative stress (reactive oxidative species). Reactive oxidative species are kept in balance by endogenous and exogenous antioxidants. Two compounds, conjugated linoleic acid (CLA) and berberine a purified compound from plant root extract have been suggested to ameliorate oxidative stress. A six-week study examined the effect of CLA and berberine supplementation on markers of oxidative-stress in poultry. Day old broiler chickens (n=60) were equally divided into six groups; a control, a CLA group where half of the regular oil used in a standard was substituted for a CLA oil mixture, a berberine group consisting of berberine supplementation, an allopurinol group, a CLA and allopurinol with the same dose as the CLA and allopurinol groups and a berberine and allopurinol group. The allopurinol was added to induce an oxidative stress state. Body weight, plasma uric acid, plasma glucose, and relative gene expression of six endogenous liver antioxidants were measured during the course of the study. The addition of allopurinol to the diet induced an oxidative stress state as measured by a significant reduction in plasma uric acid. There were no significant changes in BW and blood glucose concentrations. There was a 10-fold increase in the relative mRNA expression of superoxide dismutase 2 and 3 as well as glutathione peroxidase 1 and 3 in CLA+ALLO and BRB+ALLO treatment groups. Notably, CLA increased the expression of uncoupling protein 19-fold compared to control, while the addition of allopurinol blocked these changes. In contrast, there was a slight increase in the uncoupling protein in the BRB+ALLO treatment. Despite the increase in mRNA expression of the antioxidants genes, these results suggest that at the dosages administered, CLA and berberine were not effective in reversing the oxidative stress induced by allopurinol.
Luis-Eder Vargas-Campos
Maestro en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Marco-A. Adams-Reyes
Acapulco de Juárez Guerrero, México. 2 Especialista en Implantología Facultad Centro Oeste Paulista FACOP, Bauru Sao Paulo Brasil.
Julio-Cesar Adams-Ocampo
Maestría en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Juan-Manuel Luna-Gomez
Especialista en Ortodoncia; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Yanet Medina-Rojas
Maestra en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Luis-Martin Vargas-Zuñiga
Doctor en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Abstract
Introduction. – In this review, one of the mechanisms that is generated in inflammation, oxidative stress, was analyzed. Inflammation is an immune system response, it is essential for survival and recovery, but it can cause damage to the body, due to oxidative stress that occurs when there is an imbalance between the production of reactive oxygen species and the body’s ability to neutralize them with Endogenous antioxidants contribute to the development of chronic diseases such as cardiovascular, diabetes, autoimmune diseases, cancer, neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s, amyotrophic lateral sclerosis.
Aim. – Evaluate the literature about inflammation from the basic to the clinical level.
Methodology. – Databases such as MEDLINE/PubMed and ScienceDirect regarding Inflammation were analyzed.
Results. – Despite recent advances in the understanding of inflammation and oxidative stress, there are still important challenges in the study and treatment of these conditions, on the one hand, it is necessary to develop more precise biomarkers to evaluate oxidative stress and inflammation in patients. On the other hand, new therapeutic approaches are needed to modulate inflammation and oxidative stress more effectively and specifically.
Conclusion. – That the study of inflammation and oxidative stress is crucial to understanding the pathophysiological bases of various chronic diseases and that advances in the field of inflammation and oxidative stress have provided new therapeutic perspectives for the treatment and prevention of chronic diseases.
Vincent Dartigue
Division of Animal and Nutritional Science, West Virginia University, Morgantown, WV
Knox Van Dyke
Department of Biochemistry, West Virginia University School of Medicine, Morgantown, WV
Hillar Klandorf
Division of Animal and Nutritional Science, West Virginia University, Morgantown, WV
Kimberly M. Barnes
Division of Animal and Nutritional Science, West Virginia University, Morgantown, WV
Abstract
Selection for rapid growth in poultry can be linked to an exaggerated state of oxidative stress (reactive oxidative species). Reactive oxidative species are kept in balance by endogenous and exogenous antioxidants. Two compounds, conjugated linoleic acid (CLA) and berberine a purified compound from plant root extract have been suggested to ameliorate oxidative stress. A six-week study examined the effect of CLA and berberine supplementation on markers of oxidative-stress in poultry. Day old broiler chickens (n=60) were equally divided into six groups; a control, a CLA group where half of the regular oil used in a standard was substituted for a CLA oil mixture, a berberine group consisting of berberine supplementation, an allopurinol group, a CLA and allopurinol with the same dose as the CLA and allopurinol groups and a berberine and allopurinol group. The allopurinol was added to induce an oxidative stress state. Body weight, plasma uric acid, plasma glucose, and relative gene expression of six endogenous liver antioxidants were measured during the course of the study. The addition of allopurinol to the diet induced an oxidative stress state as measured by a significant reduction in plasma uric acid. There were no significant changes in BW and blood glucose concentrations. There was a 10-fold increase in the relative mRNA expression of superoxide dismutase 2 and 3 as well as glutathione peroxidase 1 and 3 in CLA+ALLO and BRB+ALLO treatment groups. Notably, CLA increased the expression of uncoupling protein 19-fold compared to control, while the addition of allopurinol blocked these changes. In contrast, there was a slight increase in the uncoupling protein in the BRB+ALLO treatment. Despite the increase in mRNA expression of the antioxidants genes, these results suggest that at the dosages administered, CLA and berberine were not effective in reversing the oxidative stress induced by allopurinol.
Luis-Eder Vargas-Campos
Maestro en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Marco-A. Adams-Reyes
Acapulco de Juárez Guerrero, México. 2 Especialista en Implantología Facultad Centro Oeste Paulista FACOP, Bauru Sao Paulo Brasil.
Julio-Cesar Adams-Ocampo
Maestría en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Juan-Manuel Luna-Gomez
Especialista en Ortodoncia; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Yanet Medina-Rojas
Maestra en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Luis-Martin Vargas-Zuñiga
Doctor en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Abstract
Introduction. – In this review, one of the mechanisms that is generated in inflammation, oxidative stress, was analyzed. Inflammation is an immune system response, it is essential for survival and recovery, but it can cause damage to the body, due to oxidative stress that occurs when there is an imbalance between the production of reactive oxygen species and the body’s ability to neutralize them with Endogenous antioxidants contribute to the development of chronic diseases such as cardiovascular, diabetes, autoimmune diseases, cancer, neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s, amyotrophic lateral sclerosis.
Aim. – Evaluate the literature about inflammation from the basic to the clinical level.
Methodology. – Databases such as MEDLINE/PubMed and ScienceDirect regarding Inflammation were analyzed.
Results. – Despite recent advances in the understanding of inflammation and oxidative stress, there are still important challenges in the study and treatment of these conditions, on the one hand, it is necessary to develop more precise biomarkers to evaluate oxidative stress and inflammation in patients. On the other hand, new therapeutic approaches are needed to modulate inflammation and oxidative stress more effectively and specifically.
Conclusion. – That the study of inflammation and oxidative stress is crucial to understanding the pathophysiological bases of various chronic diseases and that advances in the field of inflammation and oxidative stress have provided new therapeutic perspectives for the treatment and prevention of chronic diseases.
Vincent Dartigue
Division of Animal and Nutritional Science, West Virginia University, Morgantown, WV
Knox Van Dyke
Department of Biochemistry, West Virginia University School of Medicine, Morgantown, WV
Hillar Klandorf
Division of Animal and Nutritional Science, West Virginia University, Morgantown, WV
Kimberly M. Barnes
Division of Animal and Nutritional Science, West Virginia University, Morgantown, WV
Abstract
Selection for rapid growth in poultry can be linked to an exaggerated state of oxidative stress (reactive oxidative species). Reactive oxidative species are kept in balance by endogenous and exogenous antioxidants. Two compounds, conjugated linoleic acid (CLA) and berberine a purified compound from plant root extract have been suggested to ameliorate oxidative stress. A six-week study examined the effect of CLA and berberine supplementation on markers of oxidative-stress in poultry. Day old broiler chickens (n=60) were equally divided into six groups; a control, a CLA group where half of the regular oil used in a standard was substituted for a CLA oil mixture, a berberine group consisting of berberine supplementation, an allopurinol group, a CLA and allopurinol with the same dose as the CLA and allopurinol groups and a berberine and allopurinol group. The allopurinol was added to induce an oxidative stress state. Body weight, plasma uric acid, plasma glucose, and relative gene expression of six endogenous liver antioxidants were measured during the course of the study. The addition of allopurinol to the diet induced an oxidative stress state as measured by a significant reduction in plasma uric acid. There were no significant changes in BW and blood glucose concentrations. There was a 10-fold increase in the relative mRNA expression of superoxide dismutase 2 and 3 as well as glutathione peroxidase 1 and 3 in CLA+ALLO and BRB+ALLO treatment groups. Notably, CLA increased the expression of uncoupling protein 19-fold compared to control, while the addition of allopurinol blocked these changes. In contrast, there was a slight increase in the uncoupling protein in the BRB+ALLO treatment. Despite the increase in mRNA expression of the antioxidants genes, these results suggest that at the dosages administered, CLA and berberine were not effective in reversing the oxidative stress induced by allopurinol.
Luis-Eder Vargas-Campos
Maestro en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Marco-A. Adams-Reyes
Acapulco de Juárez Guerrero, México. 2 Especialista en Implantología Facultad Centro Oeste Paulista FACOP, Bauru Sao Paulo Brasil.
Julio-Cesar Adams-Ocampo
Maestría en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Juan-Manuel Luna-Gomez
Especialista en Ortodoncia; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Yanet Medina-Rojas
Maestra en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Luis-Martin Vargas-Zuñiga
Doctor en Ciencias; Universidad Autónoma de Guerrero, Facultad de Odontología, Laboratorio de Ciencias Básicas, Acapulco de Juárez Guerrero, México.
Abstract
Introduction. – In this review, one of the mechanisms that is generated in inflammation, oxidative stress, was analyzed. Inflammation is an immune system response, it is essential for survival and recovery, but it can cause damage to the body, due to oxidative stress that occurs when there is an imbalance between the production of reactive oxygen species and the body’s ability to neutralize them with Endogenous antioxidants contribute to the development of chronic diseases such as cardiovascular, diabetes, autoimmune diseases, cancer, neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s, amyotrophic lateral sclerosis.
Aim. – Evaluate the literature about inflammation from the basic to the clinical level.
Methodology. – Databases such as MEDLINE/PubMed and ScienceDirect regarding Inflammation were analyzed.
Results. – Despite recent advances in the understanding of inflammation and oxidative stress, there are still important challenges in the study and treatment of these conditions, on the one hand, it is necessary to develop more precise biomarkers to evaluate oxidative stress and inflammation in patients. On the other hand, new therapeutic approaches are needed to modulate inflammation and oxidative stress more effectively and specifically.
Conclusion. – That the study of inflammation and oxidative stress is crucial to understanding the pathophysiological bases of various chronic diseases and that advances in the field of inflammation and oxidative stress have provided new therapeutic perspectives for the treatment and prevention of chronic diseases.
Vincent Dartigue
Division of Animal and Nutritional Science, West Virginia University, Morgantown, WV
Knox Van Dyke
Department of Biochemistry, West Virginia University School of Medicine, Morgantown, WV
Hillar Klandorf
Division of Animal and Nutritional Science, West Virginia University, Morgantown, WV
Kimberly M. Barnes
Division of Animal and Nutritional Science, West Virginia University, Morgantown, WV
Abstract
Selection for rapid growth in poultry can be linked to an exaggerated state of oxidative stress (reactive oxidative species). Reactive oxidative species are kept in balance by endogenous and exogenous antioxidants. Two compounds, conjugated linoleic acid (CLA) and berberine a purified compound from plant root extract have been suggested to ameliorate oxidative stress. A six-week study examined the effect of CLA and berberine supplementation on markers of oxidative-stress in poultry. Day old broiler chickens (n=60) were equally divided into six groups; a control, a CLA group where half of the regular oil used in a standard was substituted for a CLA oil mixture, a berberine group consisting of berberine supplementation, an allopurinol group, a CLA and allopurinol with the same dose as the CLA and allopurinol groups and a berberine and allopurinol group. The allopurinol was added to induce an oxidative stress state. Body weight, plasma uric acid, plasma glucose, and relative gene expression of six endogenous liver antioxidants were measured during the course of the study. The addition of allopurinol to the diet induced an oxidative stress state as measured by a significant reduction in plasma uric acid. There were no significant changes in BW and blood glucose concentrations. There was a 10-fold increase in the relative mRNA expression of superoxide dismutase 2 and 3 as well as glutathione peroxidase 1 and 3 in CLA+ALLO and BRB+ALLO treatment groups. Notably, CLA increased the expression of uncoupling protein 19-fold compared to control, while the addition of allopurinol blocked these changes. In contrast, there was a slight increase in the uncoupling protein in the BRB+ALLO treatment. Despite the increase in mRNA expression of the antioxidants genes, these results suggest that at the dosages administered, CLA and berberine were not effective in reversing the oxidative stress induced by allopurinol.
Max Oliver Mackay Walker
Department of Biochemistry, School of Biomedical Science, University of Otago, Dunedin, New Zealand
Katherine H Hall
Department of General Practice and Rural Health, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand
Katie Peppercorn
Department of Biochemistry, School of Biomedical Science, University of Otago, Dunedin, New Zealand
Warren Perry Tate
Department of Biochemistry, School of Biomedical Science, University of Otago, Dunedin, New Zealand
Abstract
Long COVID is now well accepted as an ongoing post-viral syndrome resulting from infection of a single virus, the pandemic SARS-CoV-2. It mirrors the post-viral fatigue syndrome, Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome, a global debilitating illness arising mainly from sporadic geographically-specific viral outbreaks, and from community endemic infections, but also from other stressors. Core symptoms of both syndromes are post-exertional malaise (a worsening of symptoms following mental or physical activity), pervasive fatigue, cognitive dysfunction (brain fog), and sleep disturbance. Long COVID patients frequently also suffer from shortness of breath, relating to the lung involvement of the SARS-CoV-2 virus. There is no universally accepted pathophysiology, or recognized biomarkers yet for Long COVID or indeed for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Clinical case definitions with very similar characteristics for each have been defined. Chronic inflammation, immune dysfunction, and disrupted energy production in the peripheral system has been confirmed in Long COVID and has been well documented in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Neuroinflammation occurs in the brain in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome as shown from a small number of positron emission tomography and magnetic resonance spectroscopy studies, and has now been demonstrated for Long COVID. Oxidative stress, an increase in reactive oxygen and reactive nitrogen species, and free radicals, has long been suggested as a potential cause for many of the symptoms seen in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, resulting from both activation of the brain’s immune system and dysregulation of mitochondrial function throughout the body. The brain as a high producer of energy may be particularly susceptible to oxidative stress. It has been shown in peripheral immune cells that the balanced production of proteins involved in regulation of the reactive oxygen species in mitochondria is disturbed in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Fluctuations in the chronic low level neuroinflammation during the ongoing course of Long COVID as well as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome have been proposed to cause the characteristic severe relapses in patients. This review explores oxidative stress as a likely significant contributor to the pathophysiology of Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, and the mechanisms by which oxidative stress could cause the symptoms seen in both syndromes. Treatments that could mitigate oxidative stress and thereby lessen the debilitating symptoms to improve the life of patients are discussed.
Miki Kosaka
1.Tsurumi University School of Dental Medicine
2. Tokyo Children’s Rehabilitation Hospital, Japan
Hidenobu Senpuku
National Institute of Infectious Disease
Asami Hagiwara
Tokyo Children’s Rehabilitation Hospital
Yoshiaki Nomura
Tsurumi University School of Dental Medicine
Nobuhiro Hanada
Tsurumi University School of Dental Medicine
Abstract
Individuals with Down syndrome (DS) are known to be highly susceptible to periodontal disease, exhibiting a rapid progression and increased severity in younger age. They are also at high risk for Alzheimer’s disease (AD) with certain risk derived from amyloid-β (Aβ) accumulation. Periodontal disease in DS individuals is related to an impaired immune system, poor oral hygiene, gingival tissue abnormalities, salivary factors, microbial factors and oxidative stress with high levels of radical oxygen resulting in genetic abnormalities. However, simultaneous assessments of these factors were not performed to clear risk factors to periodontal disease in DS individuals. This study investigated relationships among various parameters in oral and systemic diseases in DS and non-DS subjects.
Thirty DS subjects and 38 non-DS subjects were enrolled in this study and their oral hygiene and oral disease status were examined. Unstimulated whole saliva and blood samples were collected to investigate the presence of periodontal bacteria, cariogenic bacteria and opportunistic pathogens; interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-α saliva concentrations; and Aβ42 plasma concentrations. Among tested parameters, Aβ42 plasma concentrations, development of periodontal diseases, S. mutans rate, lactobacilli per total streptococci ratio, numbers of Candida and IL-6 and IL-8 saliva concentrations were significantly higher in DS subjects than in control subjects. Additionally, oral disease parameters, except for the decay-missing-filled index, were significantly higher in DS subjects than control subjects. However, no significant difference was observed in periodontal bacteria ratios between DS and control subjects.
Our results demonstrate that DS subjects are more likely to develop periodontal diseases, produce inflammatory cytokines and become infected by opportunistic pathogens in the oral cavity than control subjects. This is likely due to poor oral hygiene and decreased host defense responses rather than infection of pathogenic bacteria or Aβ accumulation.
Subhajit Mahanty
Research Assistant, Department of Zoology, Bankura Sammilani College, Kenduadihi, PIN 722102
Dipankar Saha
Research Assistant, Department of Zoology, Bankura Sammilani College, Kenduadihi, PIN 722102
Soumitra Kumar Choudhuri
Former Emeritus Medical Scientist and Head, dept. of IVCCC, Chittaranjan National Cancer Institute (CNCI), 37 S.P. Mukherjee Road, Kolkata, PIN 700026
Surajit Majumder
Associate Professor, Department of Zoology, Bankura Sammilani College, Kenduadihi, PIN 722102
Abstract
Reactive oxygen species (ROS) are recognized as essential participants in normal cellular processes, while their intricate involvement in the emergence of various diseases, notably cancer, has garnered significant attention. Elevated levels of ROS isassociated with pro-tumorigenic signalling, heightened cell survival, increased proliferation, and DNA damage, thereby making substantial contributions to the genetic instability. Intriguingly, at elevated levels, ROS paradoxically initiate anti-tumorigenic signalling pathways, thereby instigating cell death through oxidative stress. In this comprehensive review, a focus is given on ROS generation, which encompasses both endogenous and exogenous sources that collectively referred to as oxidative stress. To provide a comprehensive understanding, an exploration of the structural, chemical, and biochemical aspects of free radicals is undertaken.Diverse sources contributing to ROS generation, including metal-mediated free radical formation is also discussed. This review additionally conducts an in-depth examination of oxidative stress within the context of cancer. Moreover, noteworthy contributions of key antioxidant enzymes, namely, superoxide dismutase, catalaseand glutathione peroxidase over the multifaceted landscape of carcinogenesis have been discussed, drawing insights from a multitude of studies. Understanding the intricate interplay between pro- and anti-tumorigenic ROS signalling pathways offers a multitude of potential avenues for cancer therapy. The disrupted redox balance observed in cancer cells presents promising opportunities for ROS manipulation, thereby emerging as a viable and innovative treatment strategy. This present review may serve as an invaluable resource, offering profound insights into the multifaceted roles of ROS in cancer while simultaneously highlighting their therapeutic potential, thereby paving the way for novel and effective cancer interventions.
Subhajit Mahanty
Research Assistant, Department of Zoology, Bankura Sammilani College, Kenduadihi, PIN 722102
Dipankar Saha
Research Assistant, Department of Zoology, Bankura Sammilani College, Kenduadihi, PIN 722102
Soumitra Kumar Choudhuri
Former Emeritus Medical Scientist and Head, dept. of IVCCC, Chittaranjan National Cancer Institute (CNCI), 37 S.P. Mukherjee Road, Kolkata, PIN 700026
Surajit Majumder
Associate Professor, Department of Zoology, Bankura Sammilani College, Kenduadihi, PIN 722102
Abstract
Reactive oxygen species (ROS) are recognized as essential participants in normal cellular processes, while their intricate involvement in the emergence of various diseases, notably cancer, has garnered significant attention. Elevated levels of ROS isassociated with pro-tumorigenic signalling, heightened cell survival, increased proliferation, and DNA damage, thereby making substantial contributions to the genetic instability. Intriguingly, at elevated levels, ROS paradoxically initiate anti-tumorigenic signalling pathways, thereby instigating cell death through oxidative stress. In this comprehensive review, a focus is given on ROS generation, which encompasses both endogenous and exogenous sources that collectively referred to as oxidative stress. To provide a comprehensive understanding, an exploration of the structural, chemical, and biochemical aspects of free radicals is undertaken.Diverse sources contributing to ROS generation, including metal-mediated free radical formation is also discussed. This review additionally conducts an in-depth examination of oxidative stress within the context of cancer. Moreover, noteworthy contributions of key antioxidant enzymes, namely, superoxide dismutase, catalaseand glutathione peroxidase over the multifaceted landscape of carcinogenesis have been discussed, drawing insights from a multitude of studies. Understanding the intricate interplay between pro- and anti-tumorigenic ROS signalling pathways offers a multitude of potential avenues for cancer therapy. The disrupted redox balance observed in cancer cells presents promising opportunities for ROS manipulation, thereby emerging as a viable and innovative treatment strategy. This present review may serve as an invaluable resource, offering profound insights into the multifaceted roles of ROS in cancer while simultaneously highlighting their therapeutic potential, thereby paving the way for novel and effective cancer interventions.
Ryan Dashek
Comparative Medicine Program, Veterinary Pathobiology, University of Missouri-Columbia, MO, USA; Research Service, Harry S. Truman Memorial Veterans Hospital, Columbia, MO, USA
Yusuke Higashi
Medicine, Tulane University School of Medicine, New Orleans, LA, USA
Nitin A. Das
Cardiothoracic Surgery, UT Health, San Antonio, TX, USA
Jacob J. Russell
Comparative Medicine Program, Veterinary Pathobiology, University of Missouri-Columbia, MO, USA; Research Service, Harry S. Truman Memorial Veterans Hospital, Columbia, MO, USA
Luis A. Martinez-Lemus
Department of Biomedical, Biological and Chemical Engineering, University of Missouri-Columbia, MO, USA; Dalton Cardiovascular Center, University of Missouri, Columbia, MO, USA; Medical Pharmacology and Physiology, University of Missouri, Columbia, MO, USA; Department of Medicine, University of Missouri School of Medicine, Columbia, MO, USA
R. Scott Rector
Research Service, Harry S. Truman Memorial Veterans Hospital, Columbia, MO, USA; Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO, USA; Division of Gastroenterology and Hepatology, Department of Medicine, University of Missouri, Columbia, MO, USA
Bysani Chandrasekar
Research Service, Harry S. Truman Memorial Veterans Hospital, Columbia, MO, USA; Dalton Cardiovascular Center, University of Missouri, Columbia, MO, USA; Medical Pharmacology and Physiology, University of Missouri, Columbia, MO, USA; Department of Medicine, University of Missouri School of Medicine, Columbia, MO, USA
Abstract
Aims: Chronic intermittent hypoxia (IH), a characteristic feature of obstructive sleep apnea (OSA), contributes to cardiovascular diseases, including atherosclerosis, potentially through persistent oxidative stress and inflammation. TRAF3IP2 (TRAF3 Interacting Protein 2) is an oxidative stress-responsive proinflammatory adapter molecule and plays a causal role in a preclinical model of atherosclerosis. Since SGLT2 (Sodium/Glucose Cotransporter 2) inhibitors have shown protective effects in CVD by inhibiting oxidative stress and inflammation, we hypothesized that IH promotes the crosstalk between oxidative stress and TRAF3IP2, resulting in IL-6-dependent human aortic smooth muscle cell (SMC) proliferation, and that these effects are inhibited by the SGLT2 inhibitor empagliflozin.
Materials and methods: Primary human aortic SMC were exposed to various cycles of IH. Normoxia served as a control. To understand the molecular mechanisms underlying IH-induced nitroxidative stress, TRAF3IP2 and IL-6 induction, and SMC proliferation and those targeted by empagliflozin were determined by treating SMC with various pharmacological inhibitors and viral vectors.
Results: IH upregulated TRAF3IP2 expression, TRAF3IP2-dependent superoxide, hydrogen peroxide and nitric oxide generation, NF-kB and HIF-1a activation, IL-6 induction, and SMC proliferation. Exposure to IL-6 by itself induced SMC proliferation in part via TRAF3IP2, IL-6R, gp130, JAK, and STAT3. Further, SMC express SGLT2 at basal conditions, and is upregulated by both IH and IL-6. Importantly, empagliflozin inhibited IH-induced TRAF3IP2 upregulation, reactive oxygen and nitrogen species generation, TRAF3IP2-dependent HIF-1a and NF-kB activation, IL-6 induction, and IL-6-dependent JAK-STAT3-mediated SMC proliferation. Moreover, empagliflozin inhibited IL-6-induced STAT3-dependent SMC proliferation.
Conclusions: These results suggest the therapeutic potential of empagliflozin in IH and inflammatory vascular proliferative diseases associated with OSA.
Raquel B. Busekrus
University of Northern Colorado, Greeley Colorado, USA
David S. Hydock
University of Northern Colorado, Greeley Colorado, USA
Abstract
Introduction: Doxorubicin is an effective chemotherapy drug, but its use is limited by its cytotoxicity. One of doxorubicin’s anticancer mechanisms is generation of reactive oxygen species which may lead to oxidative stress. The kidney, however, is very vulnerable to oxidative stress, and one way to manage oxidative stress is to scavenge reactive oxygen species via antioxidant enzymes. Although doxorubicin-induced oxidative stress has been extensively studied, a viable treatment to attenuate doxorubcin side effects has yet to be found. This study investigated the effect of creatine feeding on catalase, glutathione peroxide, and superoxide dismutase-1 expression in the kidney following doxorubicin treatment.
Methods: Twenty-eight male Sprague-Dawley rats were randomly assigned to four groups, control saline (C+SAL, n=7), control doxorubicin (C+DOX, n=7), creatine saline (Cr+SAL, n=6) and creatine doxorubicin (Cr+DOX, n=8). Control groups were fed normal chow, and creatine groups were fed chow supplemented with 3% creatine. After two weeks of feeding, doxorubicin groups received15 mg/kg doxorubicin whereas saline groups received saline as a placebo. Western blotting was used to access antioxidant enzyme expression in renal tissue.
Results: A significant between group difference was observed with catalase expression, but post hoc testing did not reveal where differences existed. A trend existed toward doxorubicin treatment increasing catalase expression and creatine attenuated this trend. Glutathione peroxidase and superoxide dismutase-1 presented a similar profile as catalase; however, no significant between group differences were observed. There was a trend, however, toward increased expression of glutathione peroxidase and superoxide dismutase-1 in doxorubicin-treated animals that seemed to be attenuated with creatine supplementation.
Conclusion: To our knowledge there are no studies exploring the antioxidant properties of creatine supplementation in the kidney with doxorubicin, and it is possible that creatine may enhance antioxidant properties that can attenuate the negative effects doxorubicin in the kidney. A trend towards antioxidant enzyme normalization promoted by creatine with doxorubicin suggests that creatine might have similar effect to that observed in previous studies using antioxidant drugs.
Raquel B. Busekrus
University of Northern Colorado, Greeley Colorado, USA
David S. Hydock
University of Northern Colorado, Greeley Colorado, USA
Abstract
Introduction: Doxorubicin is an effective chemotherapy drug, but its use is limited by its cytotoxicity. One of doxorubicin’s anticancer mechanisms is generation of reactive oxygen species which may lead to oxidative stress. The kidney, however, is very vulnerable to oxidative stress, and one way to manage oxidative stress is to scavenge reactive oxygen species via antioxidant enzymes. Although doxorubicin-induced oxidative stress has been extensively studied, a viable treatment to attenuate doxorubcin side effects has yet to be found. This study investigated the effect of creatine feeding on catalase, glutathione peroxide, and superoxide dismutase-1 expression in the kidney following doxorubicin treatment.
Methods: Twenty-eight male Sprague-Dawley rats were randomly assigned to four groups, control saline (C+SAL, n=7), control doxorubicin (C+DOX, n=7), creatine saline (Cr+SAL, n=6) and creatine doxorubicin (Cr+DOX, n=8). Control groups were fed normal chow, and creatine groups were fed chow supplemented with 3% creatine. After two weeks of feeding, doxorubicin groups received15 mg/kg doxorubicin whereas saline groups received saline as a placebo. Western blotting was used to access antioxidant enzyme expression in renal tissue.
Results: A significant between group difference was observed with catalase expression, but post hoc testing did not reveal where differences existed. A trend existed toward doxorubicin treatment increasing catalase expression and creatine attenuated this trend. Glutathione peroxidase and superoxide dismutase-1 presented a similar profile as catalase; however, no significant between group differences were observed. There was a trend, however, toward increased expression of glutathione peroxidase and superoxide dismutase-1 in doxorubicin-treated animals that seemed to be attenuated with creatine supplementation.
Conclusion: To our knowledge there are no studies exploring the antioxidant properties of creatine supplementation in the kidney with doxorubicin, and it is possible that creatine may enhance antioxidant properties that can attenuate the negative effects doxorubicin in the kidney. A trend towards antioxidant enzyme normalization promoted by creatine with doxorubicin suggests that creatine might have similar effect to that observed in previous studies using antioxidant drugs.
Jelani I
Department of Chemical Pathology, School of Medical Laboratory Sciences, Usmanu Danfodiyo University, Sokoto P.M.B. 2346, Sokoto, Nigeria
Abdullahi HL
Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, Bayero University, Kano, P.M.B. 3011, Kano, Nigeria
Alhassan AJ
Department of Biochemistry, Faculty of Basic Medical Sciences Bayero University, Kano, P.M.B. 3011, Kano, Nigeria
Dalhatu MM
Biochemistry Department, Aliko Dangote University of Science and Technology, Wudil, Kano P.M.B. 3244, Nigeria.
Dangambo MA
Department of Biochemistry, Faculty of Basic Medical Sciences Bayero University, Kano, P.M.B. 3011, Kano, Nigeria
Abacha FZ
Department of Medical Laboratory Science, College of Medical Sciences, University of Maiduguri, P.M.B. 1069, Maiduguri, Nigeria
Haruna S
Department of Medical Laboratory Science, Faculty of Allied Health Science, College of Medicine, Ahmadu Bello University, Zaria, P.M.B. 1096, Samaru Zaria, Nigeria
Mahmud RI
Kebbi State College of Health Sciences and Technology Jega, P.M.B. 9003, Kebbi, Nigeria
Yandutse MI
Department of Chemical Pathology, Federal Teaching Hospital, Katsina, P.M.B. 2121, Katsina, Nigeria
Hamza HD
Department of Chemical Pathology, Federal Teaching Hospital, Katsina, P.M.B. 2121, Katsina, Nigeria
Abdu R
Ministry of Defence, Ship House, P.M.B. 196, Abuja, Nigeria
Musa AH
Department of Medical Laboratory Science, College of Medical Sciences, University of Maiduguri, P.M.B. 1069, Maiduguri, Nigeria
Abstract
Glucose-6-phosphate dehydrogenase deficiency is a significant public health problem that is implicated in the pathogenesis of a number of common diseases via increased oxidative stress and a decrease in the generation of nitric oxide. There is little information about its impact on some organ, hence the need for this research. This was a case-control study carried out on Hausa and Fulani ethnics in Kano. Heparinized 5 ml venous blood specimen were collected from 140 individuals (70 deficient and 70 control) aged between 18-35 years selected for the study to determine the blood levels of some biochemical parameters using standard methods. There were significant increase in transaminases (p<0.001), but significant decrease concentrations of sodium (p<0.05), chloride (p<0.001), alkaline phosphatase (p<0.001) and total protein (p<0.001) whereas there was no statistically significant difference (p>0.05) in the plasma concentration of albumin, total bilirubin, conjugated bilirubin, urea, creatinine, potassium and bicarbonate ions. Our results demonstrate extremely significantly lower (p<0.001 for all) concentration in glutathione reductase, total antioxidants potential, copper, zinc and non-significant decrease (p>0.05) in manganese level of G-6-PD deficient patients compared to controls, whereas malondialdehyde level showed an increasing trend on contrary. However, there were correlations between G-6-PD activity and oxidative stress markers. The findings of the present study suggest that liver and kidneys functions were not altered among people living with G-6-PD deficiency but induce oxidative stress which is not capable of causing organ impairment.
Raquel B. Busekrus
University of Northern Colorado, Greeley Colorado, USA
David S. Hydock
University of Northern Colorado, Greeley Colorado, USA
Abstract
Introduction: Doxorubicin is an effective chemotherapy drug, but its use is limited by its cytotoxicity. One of doxorubicin’s anticancer mechanisms is generation of reactive oxygen species which may lead to oxidative stress. The kidney, however, is very vulnerable to oxidative stress, and one way to manage oxidative stress is to scavenge reactive oxygen species via antioxidant enzymes. Although doxorubicin-induced oxidative stress has been extensively studied, a viable treatment to attenuate doxorubcin side effects has yet to be found. This study investigated the effect of creatine feeding on catalase, glutathione peroxide, and superoxide dismutase-1 expression in the kidney following doxorubicin treatment.
Methods: Twenty-eight male Sprague-Dawley rats were randomly assigned to four groups, control saline (C+SAL, n=7), control doxorubicin (C+DOX, n=7), creatine saline (Cr+SAL, n=6) and creatine doxorubicin (Cr+DOX, n=8). Control groups were fed normal chow, and creatine groups were fed chow supplemented with 3% creatine. After two weeks of feeding, doxorubicin groups received15 mg/kg doxorubicin whereas saline groups received saline as a placebo. Western blotting was used to access antioxidant enzyme expression in renal tissue.
Results: A significant between group difference was observed with catalase expression, but post hoc testing did not reveal where differences existed. A trend existed toward doxorubicin treatment increasing catalase expression and creatine attenuated this trend. Glutathione peroxidase and superoxide dismutase-1 presented a similar profile as catalase; however, no significant between group differences were observed. There was a trend, however, toward increased expression of glutathione peroxidase and superoxide dismutase-1 in doxorubicin-treated animals that seemed to be attenuated with creatine supplementation.
Conclusion: To our knowledge there are no studies exploring the antioxidant properties of creatine supplementation in the kidney with doxorubicin, and it is possible that creatine may enhance antioxidant properties that can attenuate the negative effects doxorubicin in the kidney. A trend towards antioxidant enzyme normalization promoted by creatine with doxorubicin suggests that creatine might have similar effect to that observed in previous studies using antioxidant drugs.
Jelani I
Department of Chemical Pathology, School of Medical Laboratory Sciences, Usmanu Danfodiyo University, Sokoto P.M.B. 2346, Sokoto, Nigeria
Abdullahi HL
Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, Bayero University, Kano, P.M.B. 3011, Kano, Nigeria
Alhassan AJ
Department of Biochemistry, Faculty of Basic Medical Sciences Bayero University, Kano, P.M.B. 3011, Kano, Nigeria
Dalhatu MM
Biochemistry Department, Aliko Dangote University of Science and Technology, Wudil, Kano P.M.B. 3244, Nigeria.
Dangambo MA
Department of Biochemistry, Faculty of Basic Medical Sciences Bayero University, Kano, P.M.B. 3011, Kano, Nigeria
Abacha FZ
Department of Medical Laboratory Science, College of Medical Sciences, University of Maiduguri, P.M.B. 1069, Maiduguri, Nigeria
Haruna S
Department of Medical Laboratory Science, Faculty of Allied Health Science, College of Medicine, Ahmadu Bello University, Zaria, P.M.B. 1096, Samaru Zaria, Nigeria
Mahmud RI
Kebbi State College of Health Sciences and Technology Jega, P.M.B. 9003, Kebbi, Nigeria
Yandutse MI
Department of Chemical Pathology, Federal Teaching Hospital, Katsina, P.M.B. 2121, Katsina, Nigeria
Hamza HD
Department of Chemical Pathology, Federal Teaching Hospital, Katsina, P.M.B. 2121, Katsina, Nigeria
Abdu R
Ministry of Defence, Ship House, P.M.B. 196, Abuja, Nigeria
Musa AH
Department of Medical Laboratory Science, College of Medical Sciences, University of Maiduguri, P.M.B. 1069, Maiduguri, Nigeria
Abstract
Glucose-6-phosphate dehydrogenase deficiency is a significant public health problem that is implicated in the pathogenesis of a number of common diseases via increased oxidative stress and a decrease in the generation of nitric oxide. There is little information about its impact on some organ, hence the need for this research. This was a case-control study carried out on Hausa and Fulani ethnics in Kano. Heparinized 5 ml venous blood specimen were collected from 140 individuals (70 deficient and 70 control) aged between 18-35 years selected for the study to determine the blood levels of some biochemical parameters using standard methods. There were significant increase in transaminases (p<0.001), but significant decrease concentrations of sodium (p<0.05), chloride (p<0.001), alkaline phosphatase (p<0.001) and total protein (p<0.001) whereas there was no statistically significant difference (p>0.05) in the plasma concentration of albumin, total bilirubin, conjugated bilirubin, urea, creatinine, potassium and bicarbonate ions. Our results demonstrate extremely significantly lower (p<0.001 for all) concentration in glutathione reductase, total antioxidants potential, copper, zinc and non-significant decrease (p>0.05) in manganese level of G-6-PD deficient patients compared to controls, whereas malondialdehyde level showed an increasing trend on contrary. However, there were correlations between G-6-PD activity and oxidative stress markers. The findings of the present study suggest that liver and kidneys functions were not altered among people living with G-6-PD deficiency but induce oxidative stress which is not capable of causing organ impairment.
Raquel B. Busekrus
University of Northern Colorado, Greeley Colorado, USA
David S. Hydock
University of Northern Colorado, Greeley Colorado, USA
Abstract
Introduction: Doxorubicin is an effective chemotherapy drug, but its use is limited by its cytotoxicity. One of doxorubicin’s anticancer mechanisms is generation of reactive oxygen species which may lead to oxidative stress. The kidney, however, is very vulnerable to oxidative stress, and one way to manage oxidative stress is to scavenge reactive oxygen species via antioxidant enzymes. Although doxorubicin-induced oxidative stress has been extensively studied, a viable treatment to attenuate doxorubcin side effects has yet to be found. This study investigated the effect of creatine feeding on catalase, glutathione peroxide, and superoxide dismutase-1 expression in the kidney following doxorubicin treatment.
Methods: Twenty-eight male Sprague-Dawley rats were randomly assigned to four groups, control saline (C+SAL, n=7), control doxorubicin (C+DOX, n=7), creatine saline (Cr+SAL, n=6) and creatine doxorubicin (Cr+DOX, n=8). Control groups were fed normal chow, and creatine groups were fed chow supplemented with 3% creatine. After two weeks of feeding, doxorubicin groups received15 mg/kg doxorubicin whereas saline groups received saline as a placebo. Western blotting was used to access antioxidant enzyme expression in renal tissue.
Results: A significant between group difference was observed with catalase expression, but post hoc testing did not reveal where differences existed. A trend existed toward doxorubicin treatment increasing catalase expression and creatine attenuated this trend. Glutathione peroxidase and superoxide dismutase-1 presented a similar profile as catalase; however, no significant between group differences were observed. There was a trend, however, toward increased expression of glutathione peroxidase and superoxide dismutase-1 in doxorubicin-treated animals that seemed to be attenuated with creatine supplementation.
Conclusion: To our knowledge there are no studies exploring the antioxidant properties of creatine supplementation in the kidney with doxorubicin, and it is possible that creatine may enhance antioxidant properties that can attenuate the negative effects doxorubicin in the kidney. A trend towards antioxidant enzyme normalization promoted by creatine with doxorubicin suggests that creatine might have similar effect to that observed in previous studies using antioxidant drugs.
Jelani I
Department of Chemical Pathology, School of Medical Laboratory Sciences, Usmanu Danfodiyo University, Sokoto P.M.B. 2346, Sokoto, Nigeria
Abdullahi HL
Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, Bayero University, Kano, P.M.B. 3011, Kano, Nigeria
Alhassan AJ
Department of Biochemistry, Faculty of Basic Medical Sciences Bayero University, Kano, P.M.B. 3011, Kano, Nigeria
Dalhatu MM
Biochemistry Department, Aliko Dangote University of Science and Technology, Wudil, Kano P.M.B. 3244, Nigeria.
Dangambo MA
Department of Biochemistry, Faculty of Basic Medical Sciences Bayero University, Kano, P.M.B. 3011, Kano, Nigeria
Abacha FZ
Department of Medical Laboratory Science, College of Medical Sciences, University of Maiduguri, P.M.B. 1069, Maiduguri, Nigeria
Haruna S
Department of Medical Laboratory Science, Faculty of Allied Health Science, College of Medicine, Ahmadu Bello University, Zaria, P.M.B. 1096, Samaru Zaria, Nigeria
Mahmud RI
Kebbi State College of Health Sciences and Technology Jega, P.M.B. 9003, Kebbi, Nigeria
Yandutse MI
Department of Chemical Pathology, Federal Teaching Hospital, Katsina, P.M.B. 2121, Katsina, Nigeria
Hamza HD
Department of Chemical Pathology, Federal Teaching Hospital, Katsina, P.M.B. 2121, Katsina, Nigeria
Abdu R
Ministry of Defence, Ship House, P.M.B. 196, Abuja, Nigeria
Musa AH
Department of Medical Laboratory Science, College of Medical Sciences, University of Maiduguri, P.M.B. 1069, Maiduguri, Nigeria
Abstract
Glucose-6-phosphate dehydrogenase deficiency is a significant public health problem that is implicated in the pathogenesis of a number of common diseases via increased oxidative stress and a decrease in the generation of nitric oxide. There is little information about its impact on some organ, hence the need for this research. This was a case-control study carried out on Hausa and Fulani ethnics in Kano. Heparinized 5 ml venous blood specimen were collected from 140 individuals (70 deficient and 70 control) aged between 18-35 years selected for the study to determine the blood levels of some biochemical parameters using standard methods. There were significant increase in transaminases (p<0.001), but significant decrease concentrations of sodium (p<0.05), chloride (p<0.001), alkaline phosphatase (p<0.001) and total protein (p<0.001) whereas there was no statistically significant difference (p>0.05) in the plasma concentration of albumin, total bilirubin, conjugated bilirubin, urea, creatinine, potassium and bicarbonate ions. Our results demonstrate extremely significantly lower (p<0.001 for all) concentration in glutathione reductase, total antioxidants potential, copper, zinc and non-significant decrease (p>0.05) in manganese level of G-6-PD deficient patients compared to controls, whereas malondialdehyde level showed an increasing trend on contrary. However, there were correlations between G-6-PD activity and oxidative stress markers. The findings of the present study suggest that liver and kidneys functions were not altered among people living with G-6-PD deficiency but induce oxidative stress which is not capable of causing organ impairment.
Jelani I
Department of Chemical Pathology, School of Medical Laboratory Sciences, Usmanu Danfodiyo University, Sokoto P.M.B. 2346, Sokoto, Nigeria
Abdullahi HL
Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, Bayero University, Kano, P.M.B. 3011, Kano, Nigeria
Alhassan AJ
Department of Biochemistry, Faculty of Basic Medical Sciences Bayero University, Kano, P.M.B. 3011, Kano, Nigeria
Dalhatu MM
Biochemistry Department, Aliko Dangote University of Science and Technology, Wudil, Kano P.M.B. 3244, Nigeria.
Dangambo MA
Department of Biochemistry, Faculty of Basic Medical Sciences Bayero University, Kano, P.M.B. 3011, Kano, Nigeria
Abacha FZ
Department of Medical Laboratory Science, College of Medical Sciences, University of Maiduguri, P.M.B. 1069, Maiduguri, Nigeria
Haruna S
Department of Medical Laboratory Science, Faculty of Allied Health Science, College of Medicine, Ahmadu Bello University, Zaria, P.M.B. 1096, Samaru Zaria, Nigeria
Mahmud RI
Kebbi State College of Health Sciences and Technology Jega, P.M.B. 9003, Kebbi, Nigeria
Yandutse MI
Department of Chemical Pathology, Federal Teaching Hospital, Katsina, P.M.B. 2121, Katsina, Nigeria
Hamza HD
Department of Chemical Pathology, Federal Teaching Hospital, Katsina, P.M.B. 2121, Katsina, Nigeria
Abdu R
Ministry of Defence, Ship House, P.M.B. 196, Abuja, Nigeria
Musa AH
Department of Medical Laboratory Science, College of Medical Sciences, University of Maiduguri, P.M.B. 1069, Maiduguri, Nigeria
Abstract
Glucose-6-phosphate dehydrogenase deficiency is a significant public health problem that is implicated in the pathogenesis of a number of common diseases via increased oxidative stress and a decrease in the generation of nitric oxide. There is little information about its impact on some organ, hence the need for this research. This was a case-control study carried out on Hausa and Fulani ethnics in Kano. Heparinized 5 ml venous blood specimen were collected from 140 individuals (70 deficient and 70 control) aged between 18-35 years selected for the study to determine the blood levels of some biochemical parameters using standard methods. There were significant increase in transaminases (p<0.001), but significant decrease concentrations of sodium (p<0.05), chloride (p<0.001), alkaline phosphatase (p<0.001) and total protein (p<0.001) whereas there was no statistically significant difference (p>0.05) in the plasma concentration of albumin, total bilirubin, conjugated bilirubin, urea, creatinine, potassium and bicarbonate ions. Our results demonstrate extremely significantly lower (p<0.001 for all) concentration in glutathione reductase, total antioxidants potential, copper, zinc and non-significant decrease (p>0.05) in manganese level of G-6-PD deficient patients compared to controls, whereas malondialdehyde level showed an increasing trend on contrary. However, there were correlations between G-6-PD activity and oxidative stress markers. The findings of the present study suggest that liver and kidneys functions were not altered among people living with G-6-PD deficiency but induce oxidative stress which is not capable of causing organ impairment.
Peter Vajdovich
Department of Clinical Pathology and Oncology, University of Veterinary Medicine, 1078, István u. 2., Budapest, Hungary
Bernadett Szabó
Department of Clinical Pathology and Oncology, University of Veterinary Medicine, 1078, István u. 2., Budapest, Hungary
Noémi Tarpataki
Department of Internal Medicine, University of Veterinary Medicine, 1078, István u. 2., Budapest, Hungary
Judit Jakus
Department of Clinical Pathology and Oncology, University of Veterinary Medicine, 1078, István u. 2., Budapest, Hungary
Abstract
Purpose: Oxidative stress is a contributor to the development of neoplasms. OS is involved in multidrug resistance, adverse events, and outcomes.
Methods: Forty- two dogs with lymphoma have been included in the study, 30 of which were treated by Cyclophosphamide – Hydroxyldaunorubicin® (doxorubicin) – Oncovin® (vincristine) – Prednisolone (CHOP)-based protocol. Tumor samples were excised for histopatholgy, immunophenotyping, Ki67%, and biochemical analyses. Thiobarbituric acid reactive substances (TBARS), reduced and oxidized glutathione (GSH, GSSG), glutathione peroxidase (GSH-Px), Cu-Zn-superoxide dismutase (SOD), ferric reducing ability (FRAP), vitamin-C, -E, retinyl palmitate and trans-retinol in red blood cell hemolysates, lymph node homogenates, and blood plasma have been measured. The results were correlated with the outcome of the chemotherapy.
Results: Median overall survival time (OST), relapse-free period (RFP) were 862 and 280 days, respectively, with adverse effects in 18 cases.
Plasma GSH levels increased with age (dogs from 1 to 6 years vs 9 to 13 years, p = 0.0385). Lymph node FRAP levels were higher in samples with higher Ki67%, and plasma GSH/GSSG ratio was lower in dogs with increased OST and RFP. Plasma retinyl palmitate levels were lower in dogs with increased RFP. Overall survival time was increased with lower lymph node TBARS (cut off: 53 nmol/mg protein), GHS-Px (cut off: 16 U/mg protein), and higher plasma all-trans-retinol (cut off: 4 mg/ml). Relapse-free period was increased with lower lymph node TBARS (cut off: 53 nmol/mg protein), lower FRAP (cut off: 6 µmol/mg) and higher SOD (cut off: 70 U/mg protein). During chemotherapy a gradual increase in plasma vitamin E and C concentrations was detected, while GSH and GSSG showed a decrease before adverse events.
Conclusion: Although oxidative stress parameters varied, some parameters, i.e. TBARS, GSH-Px, SOD, FRAP measured in lymph node samples, and plasma all-trans retinol might be used as prognostic indices.
Akira T Kawaguchi
Department of Innovative Medical Science, Tokai University/ Department of Molecular Chemistry and Biochemistry, Doshisha University
Tatsuhide Tanaka, PhD
Department of Anatomy and Neuroscience, Nara Medical University
Mariko Yamano, PhD
Department of Anatomy and Neuroscience, Nara Medical University
Hideaki Sumiyoshi, PhD
Department of Innovative Medical Science, Tokai University
Hiroaki Kitagishi, PhD
Department of Molecular Chemistry and Biochemistry, Doshisha University
Yoshiyuki Yamada, MD, PhD
Department of Pediatrics, Tokai University
Gen T Kawaguchi, MD
Department of Plastic Surgery, Tokai University
Jacob Bergsland, MD, PhD
Oslo University Hospital
Abstract
Objective: Effects of PEGylated-carboxyhemoglobin bovine (SG) infusion and carbon monoxide (CO) inhalation were compared in a rat model of myocardial infarction (MI).
Methods: Lewis rats with induced MI received either 10 mL/kg of SG or of saline (SL), or 400 ppm CO inhalation (CO) daily for 3 days, 4 doses in total. On the fourth day, all animals had left ventricular (LV) functions studied by pressure-volume relationship analyses or in-situ myocardial gene expression by polymerase-chain reaction (PCR).
Results: Both SG infusion and CO inhalation increased the arterial carboxyhemoglobin fraction to 10%, which decreased the total O2 content by 10% for 3 hours before returning to control level, except for the plasma hemoglobin (Hb) over 200 mg/dL 24 hours later, in SG rats. Four days after MI, the SL and CO rats had enhanced cardiac contraction and relaxation, while the SG rats had LV end-systolic pressure, and the isovolumic contraction as well as relaxation remained suppressed at the post-MI levels. PCR showed significant reductions in in-situ antioxidant transcriptional master regulator (Nrf2), its down-stream antioxidant response genes (Nqo-1), hypoxic signal transduction in SG compared to SL or CO rats with enhanced pro-inflammatory, pro-apoptotic genes, and myocardial damage. These cardiac indices were reversed 4 weeks after MI, when SG had less LV dilatation, dysfunction, and myoglobin loss than those with SL or CO.
Conclusion: The results suggest that repeated SG infusion, but not CO inhalation, generates less oxidative stress, reduces hypoxic responses, supports early hemodynamics, and alleviates cardiac compensation early after MI, resulting in attenuated LV dilatation, dysfunction, and myoglobin loss late after MI in this rat model.
Keywords: Artificial Oxygen Carrier, Myocardial Infarction, HBOCs, Carbon Monoxide, Oxidative Stress, Antioxidant Response genes, Cardiac Function
Jeong-Do Kim
Department of Biological Sciences, Louisiana State University, 202 Life Science Building, Baton Rouge, LA 70803
Young-Sun Yim
Department of Biological Sciences, Louisiana State University, 202 Life Science Building, Baton Rouge, LA 70803
Michal Brylinski
Department of Biological Sciences, Louisiana State University, 202 Life Science Building, Baton Rouge, LA 70803
Raafat El-Maghrabi
Department of Physiology and Biophysics, State University of New York at Stony Brook, School of Medicine, Basic Science Tower, T-6, Room168, Stony Brook, NY, 11794-8661
Yong Lee
Department of Biological Sciences, Louisiana State University, 202 Life Science Building, Baton Rouge, LA 70803
Abstract
To understand PFKFB3 control by covalent modifications, the structure/function effect of protein arginine methyl transferase 1-dependent asymmetric di-methylations at Arg131 and Arg134 (N-CH3) and its relationship to S-glutathionylation at Cys206 (S-Gsh) was investigated. Distinctly from the report that N-CH3 is for protection of PFKFB3 from the APC/C-Cdh-mediated polyubiquitination and proteolysis, an increase in the activity for Fru-2,6-P2 production was shown from a molecular simulation and in-vitro tests. The simulation suggested that N-CH3 would uncouple the Fru-6-P entry turn (-130TRERRH-) from its coupling to the p-helix (-204DKCDRD-) by disabling the interaction between Arg131/134 and Asp207. The uncoupling consequently is likely to facilitate the Fru-6-P binding by enhancing the conformational flexibility.
Confirming the simulation, N-CH3 was shown to cause a 5-fold increase in the specific activity (kcat/Km) mostly through a 4-fold decrease in Kms for Fru-6-P. A similar extent of activation was induced by Asp207àA mutagenesis, which disables the coupling, while the activation by N-CH3 was almost abolished by Arg131àA mutagenesis. More interestingly, PFKFB3 with N-CH3 could be additionally S-glutathionylated at Cys206, when oxidative stress is elevated. When modified by both N-CH3 and S-Gsh, the activity was decreased, as if there was no N-CH3 at all, suggesting that the deactivation completely overrules the activation.
When HeLa cells were treated for the dual modifications of PFKFB3, the overruling deactivation effect of S-Gsh was prevalent, causing decreases in Fru-2,6-P2 levels and increases in glycolytic flux redirected to the pentose phosphate pathway. As a result, the levels of NADPH and reduced glutathione were markedly elevated, enhancing cell viability under the conditions of elevated oxidative stress. Altogether, it is suggested that the functional effect of S-Gsh, which represents a mechanism for survival under detrimental oxidative stress, dominates over the effect of N-CH3, which has been suggested as a mechanism for growth.
Rima Dada
Molecular Reproduction and Genetics Facility, Department of Anatomy, AIIMS, New Delhi, India
Surabhi Gautam
Molecular Reproduction and Genetics Facility, Department of Anatomy, AIIMS, New Delhi, India
Tanuj Dada
Department of Ophthalmology, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, AIIMS, New Delhi, India
Prabhakar Tiwari
Molecular Reproduction and Genetics Facility, Department of Anatomy, AIIMS, New Delhi, India
Manoj Kumar
Molecular Reproduction and Genetics Facility, Department of Anatomy, AIIMS, New Delhi, India
Abstract
Complex and chronic lifestyle disorders have become the leading cause of death and disability worldwide. They involve multiple morbidities necessitating the attention of numerous healthcare facilities as well as community-based care too. Stress and anxiety brought on by the fast-paced life, unhealthy eating habits, sedentary lifestyle, poor quality of life, polypharmacy, and high medical costs have significantly influenced the development of such multimorbid conditions. Most chronic complex diseases share a similar underlying pathology including high levels of stress, inflammatory immune response, persistent activation of the hypothalamo-pituitary-adrenal axis, oxidative stress, accelerated immune-aging, dysregulated blood flow, enhanced apoptosis and accelerated aging with shorter telomeres and DNA damage. These are modifiable factors which can impact disease progression and no single treatment modality in modern medicine can alone impact all these factors. As a result, the treatment must involve an integrated approach that targets both mind and body and each of these factors which form an architectural framework which supports the onset of these complex lifestyle disease and thus though we may enjoy longer lifespan, but it is accompanied by shorter health span. Yoga, a mind-body intervention with Indian roots, strives to bring about the synchronization of physical and mental health by unraveling and switching on the internal pharmacy and maintenance of homeostasis at cellular and molecular level.
Challenges and Opportunities in Vaccines
Special Issue:
Challenges and Opportunities in Vaccines
Enrique Chacon-Cruz
Think Vaccines LLC, Houston, Texas, USA.
Erika Zoe Lopatynsky-Reyes
Think Vaccines LLC, Houston, Texas, USA.
Kapil Maithal
Zydus Lifesciences Limited, Ahmedabad, Gujarat, India.
Sabrina Bakeera-Kitaka
Department of Paediatrics, Makerere College of Health Sciences, Kampala, Uganda.
Collins Ankunda
Department of Pharmacology and Therapeutics, Makerere College of Health Sciences, Kampala, Uganda.
Javier Casellas
Allergy, Respiratory, Infectious Diseases and Vaccines Team, IQVIA, Buenos Aires, Argentina.
Malook Vir Singh
IQVIA RDS (India) Private Limited, Noida, India.
Frederic Nikiema
Institut de Recherche en Sciences de la Santè, IRSS, Bobo Dioulasso, Burkina Faso.
Jessabelle E. Basa
Research Institute for Tropical Medicine, Department of Health, Philippines.
Mahmud Sheku
Department of Population Health Sciences, School of Public Health, Georgia State University, Atlanta, Georgia, USA.
Oscar E. Zazueta
Harvard T.H, Chan School of Public Health. Department of Epidemiology. Boston, MA, USA.
Abstract
Pertussis in a highly infectious respiratory disease, and even though vaccination has been globally implemented since the 1940s, we are far from elimination, and even still suffering from many outbreaks throughout the world.
This comprehensive review is tailored primarily for clinicians and healthcare practitioners, aiming to deepen their insights into the evolving dynamics of Pertussis over time since the first whole-cell Pertussis vaccine was started. It delves into the high reactogenicity and alleged severe neurologic effects, which were later conclusively disproven. The ensuing repercussions of these early challenges manifested in multiple outbreaks, compelling the scientific community to respond proactively. This led to the development and subsequent implementation of acellular Pertussis vaccines, marked by an improved safety profile.
Moreover, the exclusive adoption of acellular Pertussis vaccines for widespread immunization in certain countries resulted in a notable surge in Pertussis cases. Subsequent investigations, conducted through both animal models and epidemiological studies, elucidated that acellular Pertussis vaccines exhibited a considerably diminished mucosal immunity. Consequently, nasopharyngeal carriage showed minimal reduction, leading to a substantial decline in indirect or herd immunity when compared to whole-cell Pertussis vaccines. Conversely, numerous developing countries presently incorporate whole-cell Pertussis vaccines either independently or in conjunction with acellular formulations. In light of this, precise recommendations must be systematically addressed to cultivate a more unified and pragmatic landscape for immunization strategies. These recommendations should be rooted in the latest scientific data and aligned with the guidelines articulated by both the World Health Organization and the Global Pertussis Initiative.
This concerted approach aims to optimize immunization practices on a global scale, fostering a harmonized and evidence-based framework for combating Pertussis. Relevant and updated issues concerning maternal, adolescent and adult vaccination are addressed, as well as the ongoing pipeline of new intramuscular and mucosal vaccines, and finally emphasizing the continuous need for improved surveillance and pharmacovigilance systems.
Ayesha Anwar, MD
Allama Iqbal Medical College
Meryem Malik, MD
Harvard University, Cambridge MA
Vaneeza Raees
Undergraduate Student at University of Washington
Maryem Anwar, MBBS, MRCGP
NHS UK
Anjum Anwar, MD
University of Washington School of Medicine
Abstract
Vaccines offer life-saving protection against diseases and keep us safe from the harmful effects. The speedy development of vaccines during COVID-19 pandemic has reduced the coronavirus’s transmissibility and severity. COVID-19 vaccine development was challenging but the global scientific collaboration and use of resources including extensive funding made it possible. COVID-19 vaccines were deployed in controlled phases for general public use, initially offering them to the first responders and those vulnerable to life threatening effects of virus. However, it was observed that the general population has widespread vaccine hesitancy. Mass media plays a critical role in influencing people’s attitudes and practices. A common man cannot comprehend correlation from causation and jumps to conclusions. Media has the power to unite the world on one platform for a common cause. It is a source for the public to seek information, but like a double ended sword, this platform that provides information, also gives misinformation. On one hand, the public uses the media to seek information for vaccine safety and efficacy and on the other hand, to propagate unverified conspiracies against vaccines. In this review, we analyze the role of mass media and public health communications in COVID-19 vaccination from December 11, 2020, to September 15, 2021, and draw scientific inferences. We have discussed vaccine hesitancy and some prominent reasons that instil fear among the public, including the implausible claims of vaccines being the carriers of Radio Frequency Identification (RFID) microchips, impairing the reproductive systems, converting humans to hybrids, and the misconceptions about herd immunity. A consequential role of media was observed in keeping the world updated and motivated by tracking the vaccine number, distribution and deployment through live dashboards. We saw an upward trend in vaccination numbers with media campaigns, social media vaccination surveys, and socio-medico evidence. Thus, we have proposed a model for developing public awareness and health promotion using media as a tool for better distribution and administration of COVID-19 vaccines. With this, health organizations can gain widespread public trust, manage anti-vaccine movements, overcome threats faced due to vaccine conspiracy theories and eventually overcome the COVID-19 and future pandemics.
Larry L Mweetwa
DDT College of Medicine, Department for Pharmacy and Pharmaceutical Sciences, P.O. Box 70587, Gaborone Botswana, Africa, Tel: +267(0)3904924/5, Cell: +267(0) 77100000 Fax: +267(0)3904935.
Derrick D Tlhoiwe
DDT College of Medicine, Department for Pharmacy and Pharmaceutical Sciences, P.O. Box 70587, Gaborone Botswana, Africa, Tel: +267(0)3904924/5, Cell: +267(0) 77100000 Fax: +267(0)3904935.
Tumelo Tlhoiwe
DDT College of Medicine, Department for Pharmacy and Pharmaceutical Sciences, P.O. Box 70587, Gaborone Botswana, Africa, Tel: +267(0)3904924/5, Cell: +267(0) 77100000 Fax: +267(0)3904935.
Kabo Osmas Tshiamo
DDT College of Medicine, Department for Pharmacy and Pharmaceutical Sciences, P.O. Box 70587, Gaborone Botswana, Africa, Tel: +267(0)3904924/5, Cell: +267(0) 77100000 Fax: +267(0)3904935.
Sody Mweetwa Munsaka
University of Zambia, School of Health Sciences, P. O. Box 32379 Lusaka, Africa.
Thatoyaone J Kenaope
Department of Pharmacy, Boitekanelo College, Plot 5824 Masetlheng Rd, Gaborone 00000, Botswana.
Getrude Mothibe
Department of Pharmacy, Boitekanelo College, Plot 5824 Masetlheng Rd, Gaborone 00000, Botswana.
Ogorogile Mokate
DDT College of Medicine, Department for Pharmacy and Pharmaceutical Sciences, P.O. Box 70587, Gaborone Botswana, Africa, Tel: +267(0)3904924/5, Cell: +267(0) 77100000 Fax: +267(0)3904935.
Emmanuel T Oluwabusola
DDT College of Medicine, Department for Pharmacy and Pharmaceutical Sciences, P.O. Box 70587, Gaborone Botswana, Africa, Tel: +267(0)3904924/5, Cell: +267(0) 77100000 Fax: +267(0)3904935.
Abstract
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) or Coronavirus was initially detected in Wuhan China in December 2019 and has subsequently resulted in the COVID-19 pandemic. The disease presents asymptomatically in some of individuals yet also causes symptoms ranging from those associated with influenza and pneumonia, acute respiratory distress syndrome (ARDS) and even death. The world is currently relying on physical (social) distancing, hygiene and repurposed medicines; however, it was predicted that an effective vaccine will be necessary to ensure comprehensive protection against COVID-19. There was a global effort to develop an effective vaccine against SARS-CoV-2 with approximately 300 vaccines in clinical trials, and over 200 more in different stages of development and anticipated that their success will change research clinical trials processes. Although every one of these vaccines comes with its own particular set of characteristics and difficulties, they were all developed as a direct result of research and development efforts that were carried out on a scale that had never been seen before. It is the first time in the history of vaccination that a worldwide immunization campaign has begun during a time of severe pandemic activity that is defined by high virus transmission. This achievement marks an important milestone in the history of vaccination. More than anything else, the most important aspect of the new game change in drug design is that the traditional drug discovery rules have been rewritten. This is especially significant for the development of vaccines, as it is possible for all clinical trials to be accelerated, which would bring a vaccine or drug molecule to market within a year rather than the traditional fifteen years for each phase of drug clinical trials. This review provides insight in respect to first generation COVID-19 vaccines, which were in clinical use as of December 2020 and focused on the Pfizer/ BioNTech/Fosun, Moderna mRNA-1273, Johnson and Johnson and AstraZeneca/Oxford AZD1222 vaccines.
Larry L Mweetwa
DDT College of Medicine, Department for Pharmacy and Pharmaceutical Sciences, P.O. Box 70587, Gaborone Botswana, Africa, Tel: +267(0)3904924/5, Cell: +267(0) 77100000 Fax: +267(0)3904935.
Derrick D Tlhoiwe
DDT College of Medicine, Department for Pharmacy and Pharmaceutical Sciences, P.O. Box 70587, Gaborone Botswana, Africa, Tel: +267(0)3904924/5, Cell: +267(0) 77100000 Fax: +267(0)3904935.
Tumelo Tlhoiwe
DDT College of Medicine, Department for Pharmacy and Pharmaceutical Sciences, P.O. Box 70587, Gaborone Botswana, Africa, Tel: +267(0)3904924/5, Cell: +267(0) 77100000 Fax: +267(0)3904935.
Kabo Osmas Tshiamo
DDT College of Medicine, Department for Pharmacy and Pharmaceutical Sciences, P.O. Box 70587, Gaborone Botswana, Africa, Tel: +267(0)3904924/5, Cell: +267(0) 77100000 Fax: +267(0)3904935.
Sody Mweetwa Munsaka
University of Zambia, School of Health Sciences, P. O. Box 32379 Lusaka, Africa.
Thatoyaone J Kenaope
Department of Pharmacy, Boitekanelo College, Plot 5824 Masetlheng Rd, Gaborone 00000, Botswana.
Getrude Mothibe
Department of Pharmacy, Boitekanelo College, Plot 5824 Masetlheng Rd, Gaborone 00000, Botswana.
Ogorogile Mokate
DDT College of Medicine, Department for Pharmacy and Pharmaceutical Sciences, P.O. Box 70587, Gaborone Botswana, Africa, Tel: +267(0)3904924/5, Cell: +267(0) 77100000 Fax: +267(0)3904935.
Emmanuel T Oluwabusola
DDT College of Medicine, Department for Pharmacy and Pharmaceutical Sciences, P.O. Box 70587, Gaborone Botswana, Africa, Tel: +267(0)3904924/5, Cell: +267(0) 77100000 Fax: +267(0)3904935.
Abstract
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) or Coronavirus was initially detected in Wuhan China in December 2019 and has subsequently resulted in the COVID-19 pandemic. The disease presents asymptomatically in some of individuals yet also causes symptoms ranging from those associated with influenza and pneumonia, acute respiratory distress syndrome (ARDS) and even death. The world is currently relying on physical (social) distancing, hygiene and repurposed medicines; however, it was predicted that an effective vaccine will be necessary to ensure comprehensive protection against COVID-19. There was a global effort to develop an effective vaccine against SARS-CoV-2 with approximately 300 vaccines in clinical trials, and over 200 more in different stages of development and anticipated that their success will change research clinical trials processes. Although every one of these vaccines comes with its own particular set of characteristics and difficulties, they were all developed as a direct result of research and development efforts that were carried out on a scale that had never been seen before. It is the first time in the history of vaccination that a worldwide immunization campaign has begun during a time of severe pandemic activity that is defined by high virus transmission. This achievement marks an important milestone in the history of vaccination. More than anything else, the most important aspect of the new game change in drug design is that the traditional drug discovery rules have been rewritten. This is especially significant for the development of vaccines, as it is possible for all clinical trials to be accelerated, which would bring a vaccine or drug molecule to market within a year rather than the traditional fifteen years for each phase of drug clinical trials. This review provides insight in respect to first generation COVID-19 vaccines, which were in clinical use as of December 2020 and focused on the Pfizer/ BioNTech/Fosun, Moderna mRNA-1273, Johnson and Johnson and AstraZeneca/Oxford AZD1222 vaccines.
Malireddy S. Reddy, BVSC (DVM)., MS., Ph.D.
International Media And Cultures, INC. (IMAC) American Dairy Food And Consulting Labs, INC. (ADFAC Labs, Inc.) Denver, CO., USA.
Abstract
The US patent 11,077,052 B1, issued in August of the year 2021, has been granted relying on the research conducted until September 2020, using the multiple mixed strain probiotics and their immunomodulins to prevent or treat COVID-19 due to SARS-CoV-2 and its limited variants. Since then the SARS-CoV-
2 virus continuously generated multiple variants with different genomic configurations, almost to the point of overriding the vaccines and medications. The objective of this research article is to evaluate the effectiveness of the invention outlined in the U.S. patent 11,077,052 B1 on the variants of SARS- CoV-2 evolved in the later years of 2020, 2021 and 2022. This research has great significance because vaccines are not totally effective because of the high rate of mutations of SARS-CoV-2 virus resulting in antigenically different variants, which are overriding the immunity conferred by vaccines. Thus, there is a definite need for a reliable alternative or adjuvant therapy, which can be used either by itself or used as adjuvant therapy along with vaccines to combat COVID-19 infection due to SAR-CoV-2 virus and its continuously mutating variants of different antigenicity. The results of this investigation proved that the use of multiple mixed strain probiotics along with their immunomodulins are effective not only on novel SARS-CoV-2 coronavirus evolved in late 2019 and mid 2020 but also the mutated variants in the later part of the years 2020, 2021, and 2022. The COVID-19 pandemic is not yet contained as of August 2022. The SARS-CoV- 2 virus has been continuously mutating generating variants which are resisting vaccines and the treatments. The death’s due to SARS -COV- 2 viral infections are attributed predominantly to cytokine storm and thrombosis resulting in ARDS (Acute Respiratory Disease Syndrome} and multi organ failure. The earlier published article thoroughly discussed about the genesis and control of cytokine storm to protect the victims. This article mainly emphasizes the Pathophysiology of thrombosis, due to SARS-CoV-2 virus and its recent multiple variants, and the ways and means of controlling it to prevent or cure COVID-19, using the multiple mixed strain probiotics and their Immunomodulins. The hormonal and enzymatic system variations causing the disturbance in homeostasis of the vascular system resulting in thrombosis, due to SARS-CoV-2 virus and its continuously evolving variants is thoroughly discussed. In addition, the infection pattern and progression of the SARS-CoV-2 virus causing endothelial cell lysis of the vascular system resulting in thrombosis has been elucidated with molecular details. The specific role of immunomodulins of the multiple mixed strain probiotics to prevent or treat COVID-19 disease induced thrombosis has also been presented. The physiological functions of individual components of the probiotics and the immunomodulins produced by the multiple mixed strain probiotics, is presented for the first time with explicitly proven molecular details, showing how they contribute individually and cumulatively to prevent or treat COVID-19 infection, due to SARS-CoV-2 virus and its multiple variants, generated during the years 2020 through 2022, to induce thrombosis.
Oscar Cobar
School of Health Sciences, University of Isthmus, Guatemala; Pharmacogenomics and Nutrigenomics Research Group, School of Chemical Sciences and Pharmacy, University of San Carlos, Guatemala.
Stella Cobar
School of Chemical Sciences and Pharmacy, University of San Carlos, Guatemala.
Abstract
Background: The World Health Organization -WHO- declares the end of COVID-19 pandemic on May 5, 2023, and the contagious and pathogenic XBB.2.3 “Acrux” begins to spread worldwide. XBB.2.3 has a higher transmission rate and greater evasive capacity of immune-generated antibodies and vaccines than the XBB.1.16 strain, the potential to evade all forms of immunity, including those conferred by current booster vaccination or by previous infections, besides that current virus vaccines and their boosters may provide little or no protection against XBB.2.3*. Those infected with XBB.2.3*, are expected to acquire more opportunistic secondary infections that contribute to the severity of the disease and more long-term problems (Post-COVID Syndrome) and a possible increase in the mortality rate.
Aim: The purpose of the manuscript is to present a systematic review on the prevalence, structural, genomic, and pathogenic characteristics of XBB.2.3 and its descendants as of May 31, 2023, emphasizing the symptoms generated in children, adults, and the elderly.
Material and methods: Original scientific articles published in Medline, Pubmed, Science Direct, Web of Science, Scopus, EBSCO and BioMed Central databases, official health organizations (WHO, CDC, ECDEC, DOH Philippines) electronic publications, and specialized media in the subject, were electronically searched to accomplish the aim of the study. Articles published in any language were included from 2020 to present using a variety of keywords in combination. The studies relevant to our review were analysed and compared.
Results and discussion: XBB.2.3 probably originated in India, but is expanding, being detected as early as Europe in mid-January 2023 and as of May 31, 2023, in more than 47 countries, including the United States, India, Philippines and Thailand. XBB.2.3* has five defining mutations; S:D253G (previously found in Lambda and Iota variants), S:P521S (new since XBB family), S:S486P and the unprecedented ORF1a:G2091S, and ORF7a:A13V. S:S486P is probably the responsible of the superior transmissibility of XBB.2.3*, appears to have a 37% rate of infection and hospitalisation, which is 3-8% higher than other sub-variants.
Conclusions: XBB.2.3* SARS-CoV-2 strain has a higher transmission rate than XBB.1.16*, exhibits a greater evasive capacity of immune-generated antibodies and vaccines than XBB.1.16*, and even has the potential to evade all forms of immunity, including those conferred by current booster vaccination or by previous infections. Those infected with XBB.2.3*, are expected to acquire more opportunistic secondary infections that contribute to the severity of the disease and more long-term problems (Post-COVID Syndrome) and a possible increase in the mortality rate. Preliminary data from the study suggest that current virus vaccines and their current boosters may provide little or no protection against XBB.2.3*. The potential consequences of XBB.2.3* underscore the importance of coordinated, proactive and productive efforts to contain its spread.
Mairi C. Noverr
Department of Microbiology and Immunology, Tulane University School of Medicine
Junko Yano
Center of Excellence in Oral and Craniofacial Biology, LSU Health School of Dentistry
Michael E. Hagensee
Section of Infectious Diseases, Department of Medicine, LSU Health New Orleans
Hui-Yi Lin
Biostatistics Program, LSU Health School of Public Health
Mary C. Meyaski
Clinical and Translational Research Center, LSU Health New Orleans
Erin Meyaski
Clinical and Translational Research Center, LSU Health New Orleans
Jennifer Cameron
Department of Microbiology, Immunology, and Parasitology, LSU Health New Orleans
Judd Shellito
Section of Pulmonary Medicine, Department of Medicine, LSU Health New Orleans
Amber Trauth
Section of Infectious Diseases, Department of Medicine, LSU Health New Orleans
Paul L. Fidel, Jr.
Center of Excellence in Oral and Craniofacial Biology, LSU Health School of Dentistry
Abstract
Mortality in COVID-19 cases was strongly associated with progressive lung inflammation and eventual sepsis. There is mounting evidence that live attenuated vaccines commonly administered during childhood, also provide beneficial non-specific immune effects, including reduced mortality and hospitalization due to unrelated infections. It has been proposed that live attenuated vaccine-associated non-specific effects are a result of inducing trained innate immunity to function more effectively against broader infections. In support of this, our laboratory has reported that immunization with a live attenuated fungal strain induces a novel form of trained innate immunity which provides protection against various inducers of sepsis in mice via myeloid-derived suppressor cells. Accordingly, we initiated a randomized control clinical trial with the live attenuated Measles, Mumps, Rubella (MMR) vaccine in healthcare workers in the greater New Orleans area aimed at preventing/reducing severe lung inflammation/sepsis associated with COVID-19 (ClinicalTrials.gov Identifier: NCT04475081). Included was an outcome to evaluate the myeloid-derived suppressor cell populations in blood between those administered the MMR vaccine vs placebo. The unanticipated emergency approval of several COVID-19 vaccines in the midst of the MMR clinical trials eliminated the ability to examine effects of the MMR vaccine on COVID-19-related health status. Unfortunately, we were also unable to show any impact of the MMR vaccine on peripheral blood myeloid-derived suppressor cells due to several inherent limitations (low percentages of blood leukocytes, small sample size), that also included a collaboration with a similar trial (CROWN CORONATION; ClinicalTrials.gov Identifier: NCT04333732) in St. Louis, MO. In contrast, monitoring the COVID-19 vaccine response in trial participants revealed that high COVID-19 antibody titers occurred more often in those who received the MMR vaccine vs placebo. While the trial was largely inconclusive, lessons learned from addressing several trial-associated challenges may aid future studies that test the non-specific beneficial immune effects of live attenuated vaccines.
Oscar Cobar
Pharmacogenomics and Nutrigenomics Research Group, School of Chemical Sciences and Pharmacy, University of San Carlos, Guatemala; Biomedical Sciences Ph.D. Program, School of Medical Sciences, University of San Carlos, Guatemala.
Stella Co
Shool of Chemical Sciences and Pharmacy, University of San Carlos, Guatemala.
Abstract
Background: JN.1 (BA.2.86.1.1) has become the dominant strain in the U.S. at the end of 2023 according to the U.S. Centers for Disease Control and Prevention. The strain is a descendant of EG.5 family that was identified in China in February 2023 and was first detected in the United States in April 2023. JN.1* SARSCoV2 lineages: JN.1 (BA.2.86.1.1), JN.1.1, JN.1.1.1, JN.1.2, JN.1.3 and recombinants XDD (EG.5.1.1/JN.1), XDK (XBB*/JN.1.1.1). There is only a single change between JN.1 and BA.2.86 in the spike protein. JN.1 has inherited more than 30 mutations in its spike protein. It also acquired a new mutation,L455S, which further decreases the ability of antibodies to bind to the virus and prevent infection. A nonspike protein that is heavily mutated in JN.1 is the NSP3 protein. There are six mutations in NSP3 protein, namely T24I, V238L, G489S, K1155R, N1708S, and A1892T. NSP3 is one of the most active proteins in the virus, playing roles in viral RNA binding, polyprotein processing, and other functions. While the exact function of these mutations is unknown, they are likely to increase the efficiency of many of these mechanisms, creating a more functional and pathogenetic virus.The N protein is heavily mutated, R203K and G204R have been mutated in most virus variants throughout the pandemic and likely improve viral replication rate. The other mutations in N may also work to improve viral replication. While the Orf8 protein is truncated in the widespread XBB.1.5 variant, it is fully present in JN.1.
The symptoms of JN.1 appear to be similar to those caused by other strains, which include sore throat, congestion, runny nose, cough, fatigue, headache, muscle aches, fever or chills, loss of sense of taste or smell, shortness of breath or difficulty breathing, nausea or vomiting and diarrhea.
Some doctors have reported that upper respiratory symptoms seem to follow a pattern of starting with a sore throat, followed by congestion and a cough.
Aim: The purpose of the manuscript is to present a systematic review on the prevalence, structural, genomic, and pathogenic characteristics of JN.1 from January 1 to February 29, 2024, emphasizing on the variant genetic characteristics, contagiousness, and potential pathogenicity.
Material and Methods: Original scientific articles published in Medline, Pubmed, Science Direct, Web of Science, Scopus, EBSCO and BioMed Central databases, official health organizations (World Health Organization, U.S. Centers for Disease Control and Prevention, European Centre for Disease Prevention and Control) electronic publications, and specialized media in the subject, were electronically searched to accomplish the aim of the study. Articles published in any language were included from January 2024 to present using a variety of keywords in combination. The studies relevant to our review were analysed and compared.
Results and Discussion: The step-change evolution of BA.2.86, combined with the immune-evading features in JN.1, has given the virus a global growth advantage well beyond the XBB.1-based lineages the world faced in 2023. Evidence suggests the human adaptive immune system could still recognise and respond to BA.286 and JN.1 effectively. Updated monovalent vaccines, tests and treatments remain effective against JN.1. There are two elements to “severity”: first if it is more ‘intrinsically’ severe (worse illness with an infection in the absence of any immunity) and second if the virus has greater transmission, causing greater illness and deaths, simply because it infects more people. The latter is certainly the case with JN.1.
Conclusions: The latest data from US-CDC shows JN.1 as the prevalent SARS-CoV-2 variant in the United States. JN.1 in January 2024, quickly increase its prevalence and surpassed other variants, including HV.1 to become the most prevalent strain in The United States of América. JN.1 has a similar transmission rate, exhibits a greater evasive capacity of immune-generated antibodies than HV.1 family of SARS-CoV-2, produce similar symptoms that of other Omicron variants, are expected not to produce an increase in hospitalizations and mortality rate and the SARS-CoV-2 vaccines recently developed by Pfizer and Moderna, must be effective against this Omicron subvariant. For now, the dominant variant JN.1 does not seem harmful in terms of creating a deadly disease but is still contagious enough to not be ignored.
Chester Spatt, Ph.D.
Tepper School of Business, Carnegie Mellon University, 5000 Forbes Ave, Pittsburgh, PA 15213, USA.
Abstract
Several fundamental principles in economics help enhance our understanding of COVID-19, including opacity and externalities. COVID-19 is a contagious disease whose spread has been difficult to manage due to opacity, as the disease is contagious prior to the presence of symptoms and in some instances testing results for the disease require a considerable time lag before they become available. This highlights the importance of alternative testing strategies to limit the extent of opacity and to manage the costs associated with accurate testing. In addition to individual tests, such strategies would include testing employees in small groups and testing for concentration of the disease in wastewater. Diminishing returns to scale, depreciation, and shocks to the underlying disease also all play an important role in understanding the effectiveness of vaccines. Externalities are central to the mechanism for transmitting contagious diseases. The strength of the externality can be reduced potentially by various preventive measures such as social distancing and masking, though quantitative studies of the efficacy of such measures can be enhanced. Further, efforts to undertake randomized trial studies of various questions related to vaccines and prevention would be helpful, especially in light of the magnitude of economic costs that have been imposed by contagious disease, such as COVID-19.
COVID-19 and other contagious diseases also have had considerable effects on the structure of the economy. This has resulted in great development of technologies to support online meetings and work and the ability to work remotely, which in turn highlights dramatic challenges to the five-day work week, the potential for stay-at-home work, the relationship between residential and office real estate and the value of contractual flexibility in the face of dramatic shocks. Some of the effects arise during the period of acute societal disease, while other aspects reflect long-term learning. The nature of societal shocks to work and income generation also has led to important questions regarding the use of societal resources and potential shocks to the overall macroeconomy.
Babalola O.E.
Department of Surgery, Bingham University, New Karu, Nigeria
Ajayi A.A ., MD, PhD
Adjunct Professor, Keck Department of Medicine, Division of Hypertension and Clinical pharmacology, Baylor College, Houston TX 77030.
Abstract
Background and aims
The covid 19 pandemic necessitated the use of old, repurposed, and new drugs, in addition to vaccines and public health measures. There are still many controversies about the efficacy and impact of some of the medications used, which need further elucidation.
We review the pharmacological properties and the place of the repurposed drug, Ivermectin (IVM) in the prophylaxis and treatment of SARS – CoV- 2 (severe acute respiratory syndrome coronavirus 2.) infection or Covid 19 disease.
Major findings: in-vitro, in-vivo, and human studies
In vitro studies in Vero/hSlam cells caused a 99.98 % inhibition of SARS – Cov-2 (5000-fold) within 48 hours. The IC50 (half maximal inhibitory concentration) for this virucidal action was 2.8μM, which was thought unattainable in humans in-vivo. Thus, there was initial skepticism on pharmacokinetic grounds as to possible efficacy of IVM in humans with Covid 19. There are, however, a multiplicity of anti-covid 19 mechanisms, beyond mere anti-viral effects, such as blockade of ACE2 receptor viral entry, and the anti-cytokine and anti-inflammatory effects of IVM. IVM has a long half-life of 18 – 24 hours, Mean Residence Time (MRT) of 3.4 days and a preferential site of lung accumulation.
In-vivo studies in Syrian Golden hamsters confirmed the symptomatic, anti-inflammatory, anti-cytokine, histopathological and survival benefit of IVM, which was more manifest in female animals.
In a January 2023 meta-analysis of studies (s) in total number of patients (n) for various parameters (p), the reduction in risk relative to placebo or controls were as follows:
- Overall improvement (s= 95) (n= 134,554) was 62% [95%CI 54-69].
- Mortality (s=48) (n=120,000) there was 51% reduction [95%CI 37-62].
- Hospitalization (s=29) (n = 44, 784), there was 34% reduction [ 95% CI 20-45].
- Viral clearance (s=20) (n= 3945) there was 45% reduction [95%CI 31-55].
- Prophylaxis (s=17) (n=19,764) showed 82% reduction [95%CI 73-88]
6 Randomised Control Trial (RCT) studies (s= 45) (n=2173) showed a 54 % mortality reduction [95% CI 39-65]
In addition, IVM has been shown in studies to cause a rapid reversal of hypoxemia (SPO2 < 94%) and a rapid increase in SPO2, an effect exhibiting a gender dichotomy. (SPO2 is the percentage of the maximum carrying capacity of the blood). This effect on SPO2 has been attributed to IVM’s reversal and prevention of SARS-CoV-2 virus induced hemagglutination. The dosage used for treatment of covid 19 varied widely within studies, but doses of 200-400 μg/kg twice weekly or daily for 5 consecutive days, caused significant viral clearance and clinical improvement, with minimal safety concerns. For prophylaxis, a dose of 200μg/kg for two consecutive days every 15 days was found effective in studies.
Conclusion: This review provides powerful evidence that IVM is efficacious singly or as a part of a regimen for covid 19. IVM could potentially be combined with newer oral anti-covid 19 agents, such as Paxlovid, for effective and life-saving regimen in patients infected with covid-19. The anti-viral properties of these drugs can synergize with the anti-inflammatory and anti-cytokine properties of Ivermectin. Ivermectin is also useful prophylactically, especially where vaccines are unavailable or undesirable.
Daniel R. Lucey, MD, MPH
Professor of Medicine Geisel School of Medicine at Dartmouth and the Dartmouth Institute for Healthcare Policy and Clinical Research, Hanover, New Hampshire, USA
Abstract
Nipah virus is a bat-borne zoonotic RNA virus discovered in Malaysia during an 1998-1999 outbreak that involved pigs, fruit bats, and humans in Malaysia (1). Clinical manifestations are primarily encephalitis and pneumonia. The case fatality rate of symptomatic cases is 40%-70%. Survivors can have severe neurologic sequelae (2-5). There are no licensed vaccines, antiviral drugs, monoclonal antibodies, or point-of-care rapid diagnostic tests, although extensive work on vaccines and monoclonal antibodies is underway (6). Person-to-person transmission, including a small number of superspreading events, has occurred in Bangladesh and India (7-9).
From 1998-2023 all reported outbreaks have been in either southeast (SE) Asia (Malaysia, Singapore, the Philippines), or south Asia (Bangladesh, India) (2, 7-10). It is likely that a future Nipah outbreak, and possibly widespread epidemic, will occur outside south/SE Asia, whether elsewhere in Asia such as China, or on another continent. When it does, then as with the COVID-19 pandemic, multiple questions will be raised regarding the origin of the epidemic. Each of the following four (4) main scenarios could be anticipated to account for the origin of such a geographically-unprecedented Nipah epidemic during analysis on Day 1 of the event by national and international organizations.
Marco Villanueva Reza
Infectious Disease Physician, Instituto Nacional Enfermedades Respiratorias
Sebastián Rodríguez-Llamazares
Division of Respirology and Sleep Medicine, Queen’s University Department of Medicine
Alvaro López Iñiguez
HIV and Infectious Disease Physician, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
Santiago Montiel Romero
Infectious Disease Physician, Centro Medico ABC (American British Cowdray Hospital)
Arturo Galindo Fraga
Deputy Director of Epidemiology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
Abstract
In Latin America, the COVID-19 pandemic, which initially surged and is now a constant presence, has brought about significant health challenges due to disparities and differences in regional responses. Vaccination is not only a necessity but also a responsibility as the primary tool for prevention. However, its implementation has not been consistent across countries, leading to various challenges such as global demand, initial high costs, infrastructure limitations for distribution, public hesitance, and misinformation. Other issues, like vaccine efficacy in immunocompromised patients and the use of different vaccines, were initially questioned but are now regarded as strategies to protect patients. This region, with its unique traditions, also faces several risk factors including vaccine supply shortages, lack of vaccine manufacturing, overcrowded cities, and an increasing migrant population that adds to the vulnerability of the people, challenging countries to strive for equity in prevention strategies. It is important to address individual strategies in communities to increase vaccine uptake as part of public health policy, and collaboration between countries should be encouraged to reach more people. This review will provide information about the COVID-19 vaccines available in the region, their characteristics and composition, their use across countries, and the reported effectiveness in the general population and among those with weakened immune systems.
Maia G Campbell
Ball State University Honors College
Dr. Jayanthi Kandiah
Ball State University College of Health
Dr. James Jones
Ball State University
Abstract
Background. The global spread of COVID-19 prompted a need for widespread vaccination to slow the transmission of the virus. Despite global, national, and local efforts, many people in various nations hesitated to receive a COVID-19 vaccine.
Aims. The objective of this systematic review was to synthesize the existing literature addressing factors influencing COVID-19 vaccine acceptance and hesitancy.
Methods. A literature search was conducted between November 2021 and March 2022. Inclusion criteria were studies identifying causations of COVID-19 vaccine acceptance and/or hesitancy since March 2020 in six developed/developing countries, Australia, Brazil, India, Nigeria, Russia, and the United States. Studies that were not originally published in English were excluded.
Results. Patterns in the factors influencing both acceptance and hesitancy toward the COVID-19 vaccines emerged. Vaccination acceptance was largely related to individuals’ personal preferences and beliefs regarding immunity, while vaccination hesitancy was attributed to fears and distrust of vaccine safety, side effects, and efficacy.
Limitations. Lack of consistency in methodical procedures and text availability by country may limit the generalizability of the findings.
Conclusion. In developed/developing nations, emerging data suggest that skepticism surrounding COVID-19 vaccines was the most prevalent factor leading to vaccination hesitancy, while factors including personal protection were largely associated with higher acceptance rates of the COVID-19 vaccine. Because widespread immunization is necessary to slow the transmission of COVID-19, it is important that factors leading to hesitation are addressed in order to increase vaccination rates and achieve herd immunity.
Ronald Cárdenas Krenz
Universidad de Lima. Universidad Pública de Navarra
Abstract
What has been experienced during the COVID-19 pandemic, especially in the most vulnerable populations, has revealed the need for a new health model, much more fair, efficient and inclusive; However, defining and applying it is particularly a complex task.
When the pandemic arrived, health systems in different parts of the world revealed their precariousness and inequality, exacerbating the vulnerability of some groups. To make matters worse, the international response once the crisis arrived revealed limited solidarity in the most difficult moments of the crisis.
Although the arrival of vaccines months later offered hope, demonstrating the importance of collective work and not the fate of nations, many people, for reasons of the most diverse nature, were reluctant to get vaccinated. So, governments, faced with the urgency of confronting the virus in the most massive and rapid way, dictated different measures, sometimes correct, sometimes controversial, with the purpose of promoting vaccination.
This intervention, beyond its results, should raise questions about the scope and limits of state intervention in health, what are the terms that the relationship between the individual and the State should have, the need for subtle measures to motivate vaccination and the possibility of applying nudges as a strategy for the effect.
The experience of the pandemic, with its millions of victims, raises the need for a global and autonomous model, taking advantage of globalization to access knowledge, produce medicines and vaccines, as well as distribute them in the most efficient way.
In this purpose, science plays a crucial role, even when its postulates are provisional. States must rebuild lost trust in their governments, and know how to balance health and the economy. The pandemic has highlighted the importance of global public goods and the need to reconcile personal and collective interests instead of opposing them.
Lessons include the need for universal health systems, balanced measures by the State and the promotion of both a culture of responsibility and an ethic of care, with persuasion preferable to imposition.
This article certainly does not seek to propose what this system should be, which requires deeper and more interdisciplinary work, but it does seek to propose some guidelines that serve as guidance in this task, based on reflection on the experiences lived in the fateful days of the pandemic.
Eliana Zeballos
USDA Economic Research Service, Food Economic Division, Washington, D.C., USA
Wilson Sinclaira
USDA Economic Research Service, Food Economic Division, Washington, D.C., USA
Keenan Marchesia
USDA Economic Research Service, Food Economic Division, Washington, D.C., USA
Abstract
The U.S. government’s efforts in response to the pandemic included the development, manufacturing, and distribution of safe and effective COVID-19 vaccines. By the end of 2020, the Food and Drug Administration issued Emergency Use Authorizations for the Pfizer-BioNTech COVID-19 and the Moderna COVID-19 vaccine. Following this authorization, on December 14, 2020, each State received allocations of vaccines and devised individual distribution plans. This study investigates the impact of COVID-19 vaccination on U.S. food spending at home and away from home in 2021 employing fixed-effects regression analysis on quarterly State-level data. The results reveal that higher vaccination rates—measured by the share of the population that is fully vaccinated—are associated with a decrease in food-at-home sales and an increase in food-away-from-home sales. Further analysis reveals nuanced shifts between full-service and limited-service restaurants, indicating increased sales at full-service establishments and decreased sales at limited-service ones, suggesting a trade-off effect between the two restaurant types. The results of this study provide valuable insights for policymakers and industry stakeholders seeking to understand the heterogenous impacts of vaccinations on food spending.
Kashif Gulzar, Dr
Nephrology Department, Dubai Hospital, Dubai, UAE.
Fakhriya Alalawi, Dr
Nephrology Department, Dubai Hospital, Dubai, UAE.
Hind Hassan Alnour, Dr
Nephrology Department, Dubai Hospital, Dubai, UAE.
Amna Khalifa AlHadari, Dr
Nephrology Department, Dubai Hospital, Dubai, UAE.
Abstract
Background: Coronavirus disease 2019 (COVID-19) is associated with increased morbidity and mortality in chronic kidney disease patients, especially those on maintenance hemodialysis (HD). The comparison of immunogenicity of different COVID vaccines in the dialysis populations is lacking especially in the middle east region.
Methods: We conducted a retrospective observational study, that includes 164 hemodialysis patients (HD) and 54 health workers (HW), who received 2 doses of either Pfizer-BioNTech or Sinopharm vaccine. The primary endpoint was to report the rate of seroconversion and the factors affecting it.
Results: HD patients have a significantly low seroconversion rate than HW (HD vs HW: 76.54% and 100%, p=<0.05), also S1 IgG antibody level was significantly low in HD patients (HD vs HW: 183.5 and 400 BAU/ml, p=<0.05). The type of vaccine and hypo-response to the HBV vaccine were two statistically significant factors affecting the seropositivity rate in HD patients. As compared to Sinopharm, Pfizer-BioNTech vaccinated HD patients exhibit not only higher seroconversion rate (Pfizer-BioNTech vs Sinopharm: 90.80% and 60%, p=<0.05) but also express high S1 antibody titer (Pfizer-BioNTech vs Sinopharm: 425 and 162 BAU/ml (p=<0.05), however, there is no significant difference in post-vaccine COVID infection rate among the two vaccines (Pfizer-BioNTech vs Sinopharm: 39.24% and 42.22% (p= 0.176).
Conclusion: Lower Immune response to the COVID vaccine is observed in HD patients as compared to HW participants, also Pfizer-BioNTech vaccinated HD patients exhibit better seroconversion rates and higher antibody titer than Sinopharm vaccine in HD patients, so alternative vaccine strategies should be designed in dialysis patients.
Ankica Kosic
Sapienza University of Rome, Italy
Corine Stella Kana Kenfack
Sapienza University of Rome, Italy
Amy L. Ai
Florida State University, USA
Abstract
The COVID-19 pandemic has led to psychological stress caused by several threats such as concerns for health, economic problems, and several others. This study aims at exploring if inner resilience and belief in spiritual support may moderate the relationship between the concerns, on one side, and distress and the attitudes towards anti-COVID-19 vaccines, on the other side. We conducted a study involving 235 participants through an online survey from March to April 2021 in Italy, immediately after the last lockdown that took place in March 2021. Several scales were used to measure various difficulties and concerns, resilience, beliefs about spiritual support, conspiracy beliefs about COVID-19, psychological distress, and acceptance of the anti-COVID-19 vaccines. We found that resilience moderates the relationship between several concerns and psychological distress during the COVID-19 pandemic, especially among the participants who have strong beliefs in spiritual support.
Jose-Luis Sagripanti
US Food and Drug Administration and US Department of Defense (RETIRED). Maryland, United States.
Daniel R. Aquilano
Laboratorio de Análisis Bioquímicos, La Plata, Prov. Buenos Aires, Argentina
Abstract
COVID-19 seems to have progressed under two general assumptions: a) every new variant of SARS-Co V-2 should bear the worst consequences, thus justifying extension of government-mandated lock-downs, school and border closures, face mask wearing and other restrictive measures and b) that hastily developed experimental vaccines employing novel technologies would quickly and efficiently stop the pandemic by protecting from infection or, at the very least, by preventing complications and death. We tested these two hypotheses by analyzing the epidemiological data officially released by the governments of six countries in South America. We found that vaccination failed to prevent contagion by Omicron or by previous variants of SARS-Co V-2. Mortality has decreased with time since the start of global COVID-19 in early 2020 with Omicron showing the lowest mortality to date. This finding cursorily agreed with a beneficial effect of vaccination in each individual country but failed when countries with similar mortalities and different vaccination rates were analyzed. Thus, the slight but continued reduction in mortality through the duration of the pandemic and sharp decrease with Omicron do not correlate with the level of national vaccination among the countries studied. A more plausible explanation for the decrease in mortality through time is the natural attenuation of SARS-Co V-2 from successive passage through millions of susceptible and healthy hosts, as dictated by well-established principles of virology, immunology, and vaccinology dating at least from the mid 1950’s. The failure to prevent infection or to substantially reduce mortality as reported here should raise questions about the value of the massive vaccination campaigns in South America, particularly, considering the potential risks of adverse reactions (still to be fully determined) to experimental vaccines and the considerable cost to the stressed national economies of the region.
Abstract
Background: The administration of the COVID-19 vaccine at some points in the COVID-19 pandemic resulted in a significant reduction in the spread, risk of complications, and death from coronavirus infection. However, in the face of hesitancy against COVID-19 vaccination springing from the novelty of the vaccines and safety concerns, vulnerable population to COVID-19 infection such as people living with HIV/AIDS (PLWHA) were showing higher hesitancy to COVID-19 vaccines than the general population. This scoping review aims to identify factors COVID-19 vaccine hesitancy among PLWHA. Methods: A scoping review was conducted to identify and summarize studies from all over the world on COVID-19 vaccine uptake/hesitancy among people living with HIV/AIDS (PLWHA). The Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) Extension for scoping reviews was used. Articles written in English, peer-reviewed, published within the years 2021-2023, and conducted in any part of the world with sample population being PLWHA, and with an outcome of uptake/hesitancy towards the COVID-19 vaccine were included. Results: Fourteen articles met the inclusion criteria and were included in this review. The primary study settings were clinic and hospital-based and online self-reported. The prevalence of COVID-19 vaccine hesitancy was as high as 90.8% in an online survey done in the US and as low as 27.5% in a facility-based survey in China. The most common factors mentioned associated with COVID-19 vaccination were the fear of side effects of the COVID-19 vaccine, concerns about the safety of the vaccine, medical mistrust, vaccine novelty, disclosure of HIV status, and perceived interference with highly active antiretroviral therapy (HAART). Male gender, race, good knowledge of COVID-19 prevention practice, having a CD4 count > 200 cells (p=0.032) and lower or undetectable viral load (p<0.001) were identified as predictors of COVID-19 uptake.
David J.A Goldsmith, FRCP
Retired physician
Eric J.W. Orlowski, MPhil
PhD Candidate
Abstract
It is the purpose of this narrative review to examine the impact of COVID-19 and the countermeasures deployed by central authorities on the health and wellbeing of children in the UK and in Sweden.
The COVID-19 pandemic of 2020-2023 was the most momentous and impactful public health event since the “Spanish Flu” pandemic of 1918-1920. Many fatalities ensued, largely but not completely confined to older subjects. However, taking a broader lens than just counting fatalities, it is clear that the pandemic exposed dramatic societal inequalities, whose impacts also were felt differently by different age groups. Health policy interventions were conceived in the main around the needs of adults, not children.
The special focus of this paper is the comparison between a full “lock down” country such as the UK, which had amongst the longest COVID-mandated school closures in the free world, and Sweden, which almost uniquely declined to impose distance learning on school children aged 15 and under. Similarly, the opportunity afforded by the immunisation of children against COVID-19 using novel vaccines was taken up to a very variable degree with some countries strongly advocating its routine use, while others only administered such vaccines to those at the highest risk of adverse outcomes (Sweden).
The authors searched (using Google Scholar and PubMed) for relevant pre-print/fully-published articles, periodicals, books, press reports, government policy pronouncements and publications for the period January 2020 to October 2023; in addition, the publicly-available outputs of the completed Swedish and ongoing UK COVID-19 enquiries were examined. Finally, a detailed in-person interview was undertaken in 2023 by one of the authors (DG) with the former State Epidemiologist of Sweden (Dr Anders Tegnell), who was in day-to-day charge of that country’s actions between 2020 and 2022.
Using these diverse lines of evidence, the authors have attempted to understand what measures were undertaken in the two countries which directly affected children’s health, why those policy choices were made, and any lessons learned which may be useful in the certain expectation of similar if not worse future pandemics.
Mahmood Dashti
Postgraduate Orthodontics Resident, Georgia School of Orthodontics, Atlanta, Georgia, USA.
Nozhan i Azim
Dental Student, Faculty of Dentistry, Tehran Islamic Azad University of Medical Sciences, Tehran, Iran.
Shohreh Ghasemi
Adjunct Assistant Professor, Department of Oral and Maxillofacial Surgery, The Dental College of Georgia at Augusta University, Augusta, Ga, USA.
Abstract
The B.1.1.529 (Omicron) variant of SARS-CoV-2 has rapidly spread with many variants like BA.1, BA.2, BA3., BA4., and BA5. With sublineages as well. It (Omicron) was first discovered in November 2021 and has become the predominant variant in several nations. Due to the sensitivity of infection and various other limitations like no particular real-time data for different age groups, there is a lack of information on the actual efficacy of vaccines against this variant. Limitations of data and reviews and the incidence of emergence rather than hospitalized people would result in an underestimation of the efficacy of vaccines against severe diseases. This systematic review was conducted by following PRISMA guidelines. Specific inclusion and exclusion parameters were strictly followed. Our studies show that a substantial number of people have received mRNA COVID-19 vaccine doses. The booster dose must be administered and obtained immediately before all efforts to stop the pandemic go to waste. Focusing on the primary vaccination is no longer sufficient.
James E. Galen
Center for Vaccine Development and Global Health, Baltimore MD 21201; University of Maryland School of Medicine, Baltimore MD 21201
Thanh Pham
Center for Vaccine Development and Global Health, Baltimore MD 21201; University of Maryland School of Medicine, Baltimore MD 21201
Abstract
Cancer remains a serious challenge to public health, with breast cancer, lung, and colorectal cancers predominating in both incidence and deaths worldwide. Significant advances have been made in the therapeutic treatment and resolution of non-solid tumors using immune checkpoint inhibitors (ICI) and chimeric antigen receptor (CAR) T cell therapy to break immune tolerance and initiate tumor clearance. However, these innovative strategies have enjoyed only limited success with solid tumors, especially in late-stage cancers in which tumor size is large. An immunosuppressive tumor microenvironment (TME) that surrounds and protects solid tumors significantly confounds the ability of the host immune system to target and eliminate tumor tissue. Novel technologies using nanomedicines have begun to yield promising results by penetrating into the microenvironment to stimulate innate immunity and induce trafficking of activated antigen presenting cells to regional lymph nodes, ultimately leading to tumor-specific adaptive immune responses. One type of nanomedicine that is generating increasing enthusiasm in the field of immunotherapy are bacterial outer membrane vesicles (OMVs) that can be genetically engineered to surface-express tumor-associated antigens; the resulting recombinant OMVs (rOMVs) can then be purified as immunotherapeutic vaccines. Recent data from experimental animal models have demonstrated remarkable efficacy in tumor challenge models. Such promising experiments suggest the possibility of translating these novel strategies into success with solid tumors in clinical trials. In this review, we will summarize current research using purified rOMVs as immunotherapeutic vaccines and further discuss potential obstacles that still need to be adequately addressed to ensure success in human trials.
Oscar Cobar
Pharmacogenomics and Nutrigenomics Research Laboratory, School of Chemical Sciences and Pharmacy, University of San Carlos, Guatemala.
Stella Cobar
School of Chemical Sciences and Pharmacy, University of San Carlos, Guatemala.
Abstract
Background: HV.1 (EG.5.1.6.1) was the dominant strain in the U.S. as of the end of second week of December 2023, according to the U.S. Centers for Disease Control and Prevention (CDC). The strain is a descendant of EG.5 family that was identified in China in February 2023 and was first detected in the United States in April 2023. 44 mutations in S-protein, 2 in Membrane and Envelope viral structures, 5 mutations in the Nucleocapsid, 21 mutations in Orf1a, 1 mutation in Orf3a, Orf6, Orf10, and 2 mutations in Orf8 virus genome open reading frames are reported. The symptoms of HV.1 are similar that of other Omicron variants, these include fever or chills, cough, shortness of breath or difficulty breathing, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea or vomiting, and diarrhea, but congestion, sore throat and dry cough seem to be the three most prominent symptoms right now. Since HV.1 belongs to the same family as XBB, health experts assumethat updated vaccines are expected to be effective against this new dominant subvariant.The only way to distinguish (COVID-19) from RSV and flu, both of which are now gaining steam, is by testing.
Aim: The purpose of the manuscript is to present a systematic review on the prevalence, structural, genomic, and pathogenic characteristics of HV.1 from October 1, 2023, as of December 31, 2023, emphasizing on the variant genetic characteristics, contagiousness, and potential pathogenicity.
Material and Methods: Original scientific articles published in Medline, Pubmed, Science Direct, Web of Science, Scopus, EBSCO and BioMed Central databases, official health organizations electronic publications, and specialized media in the subject, were electronically searched to accomplish the aim of the study. Articles published in any language were included from October 2023 to present using a variety of keywords in combination. The studies relevant to our review were analysed and compared.
Results and Discussion: HV.1 showed significantly lower plasma neutralisation titers compared with their parental strains after acquiring L452R and A475V mutations, explaining their growth advantages. A475V mutation also resulted in decreased binding affinity, enhancing immune evasion compared to HK.3 (XBB.1.5+FLip). However, the L452R mutation of HV.1 did not affect binding affinity. 44 mutations in S-protein, 2 in Membrane and Envelope viral structures, 5 in the Nucleocapsid, 21 in Orf1a, 1 mutation in Orf3a, Orf6, Orf10, and 2 in Orf8 virus genome open reading frames mutations are reported. These mutations give to HV.1 improved ability to enter the human cell, although no greater pathogenicity or severity of the symptoms.
Conclusions: The latest data from US-CDC in 2023, shows HV.1 as the second prevalent SARS-CoV-2 variant in the United States. HV.1 (XBB.1.9.2.5.1.6.1 or EG.5.1.6.1) in October 2023, quickly increase its prevalence and surpassed other variants, includingEG.5 (Eris) to become the most prevalent strain in USA until week ending on December 9, 2023. HV.1 has a similar transmission rate, exhibits a greater evasive capacity of immune-generated antibodies than EG.5.1* family of SARS-CoV-2, produce similar symptoms that of other Omicron variants, are expected not to produce an increase in hospitalizations and mortality rate and the SARS-CoV-2 vaccines recently developed by Pfizer and Moderna, must be effective against this Omicron subvariant.For now HV.1 does not seem harmful in terms of creating a deadly disease but is still contagious enough to not be ignored.
Anushka Ashok
Final Mile Consulting, Mumbai, India
Sangiwe Moyo
Final Mile Consulting, Johannesburg, South Africa
Saransh Sharma
Final Mile Consulting, New York, USA
Laura Myers
Final Mile Consulting, Johannesburg, South Africa
Abstract
In addition to the direct health and economic impacts of the COVID-19 pandemic, routine immunization of children for vaccine-preventable diseases has also suffered. Quantitative studies have shown evidence of backsliding in routine immunization, i.e., children failing to receive their vaccinations on schedule. Pandemic restrictions were the cause for some of this behavior, and there are signs that subsequent campaigns and supply-side initiatives have influenced trends toward routine immunization catch-up. However, limited qualitative research indicates that the pandemic may have disrupted parents/caregivers’ decision-making processes around routine immunization, and their attitudes toward vaccination, in ways that could have long-term effects on rates of immunization. Further behavioral research can help elucidate this and provide guidance to policymakers to boost immunization uptake.
This policy article explores the decision dynamics leading to missed routine immunization doses during the pandemic, through an analysis of secondary literature, a summary of primary-research studies on COVID-19 vaccine hesitancy conducted during the pandemic across Côte d’Ivoire, Burkina Faso, Kenya and Pakistan, and a summary of a study on the impact of COVID-19 on routine immunization uptake in South Africa.
We found that the COVID-19 pandemic severely disrupted prior patterns of engagement with the health system, turning routine immunization from a default decision for parents/caregivers into an “active decision-making” moment. Restrictions on movement, limited routine immunization supplies and other practical impediments combined with fear of contracting COVID-19 at health facilities, misinformation, and fear of vaccine side-effects, creating an emergent behavior of missed immunization doses during the pandemic period. We also found that hesitancy about COVID-19 vaccines may be transferred onto previously accepted vaccines, impacting routine immunization.
We identified three decision-making pathways for routine immunization uptake among South African parents/caregivers once the lockdowns were lifted: the “path of procrastination,” the “path of doubt,” and the “path of persistence.” We highlight the policy implications of these, and suggest potential interventions to increase routine immunization uptake for parents/caregivers on each path, as well as for general communications, service delivery, and pandemic readiness.
Abstract
Annually, 59,000 people die of rabies, the world’s oldest known infectious disease, globally. In the United States, canine rabies has been virtually eliminated but the risk of rabies due to wildlife, especially raccoons, skunks, and bats, has required post exposure prophylaxis (PEP) be administered to more than 60,000 patients annually1. In 2021, 5 people in the United States2 died of rabies mostly due to misinformation or improper treatment. Rabies post exposure prophylaxis consists of three steps, wound washing, administration of human rabies immune globulin (HRIG) and a full course of vaccine3. In 2022, Whitehouse4 published that there were 122 breakthrough rabies infections when PEP was given due to four factors: 1) deviations from core practice 2) delays in seeking health care 3) errors in administration of HRIG 4) comorbidities or immunosuppression. It is estimated that over 40% of PEP administration is given inappropriately.
The publication,” Safety, and efficacy of rabies immunoglobulin in pediatric patients with suspected exposure”, Human Vaccines & Immunotherapeutics, 17:7, 2090–20965, was the first study that prospectively reviewed the use of human rabies immune globulin 150 IU/ml in 30 pediatric patients ages 0.5–14.9 years old.
Globally, 40% of people bitten by animals suspected of being infected with the rabies virus are children under the age of 15.6
This paper will look at risk reduction strategies that will include:
- Proper Identification of major rabies vectors
- Special risks associated with bat exposures in children
- Administration of human rabies immune globulin with volume considerations in children
- Special administration consideration for rabies vaccines
- “Just -in- time “Education for health care providers
Illustrative cases will be used to demonstrate each of these strategies of risk as well as the strategies for risk reduction.
Shaun Dennis Black
The University of Texas at Tyler
Abstract
COVID-19 disease is caused by the Betacoronavirus, SARS-CoV-2. This virus gave rise to 676 million confirmed cases with 6.9 million deaths worldwide by early 2023. After first appearing in Wuhan, China in late 2019, the virus has mutated into seven successive major forms with progressive increases in infectivity: Alpha, Beta, Delta, Omicron, and Omicron variants BA.4, BA.5, and XBB.1.5. Liposomal mRNA vaccines have been developed against SARS-CoV-2. Many of these received Emergency-use Authorization, and all have been highly promoted by civil authorities and the media. On the other hand, therapeutics against COVID-19 have been developed, but some of these have been severely suppressed, even by reliance on retracted papers. Our laboratory found that chlorpheniramine maleate, an over-the- counter antihistamine, was active against the Coronavirus through drug-database searches, molecular modeling, and a preliminary retrospective clinical-study. The manuscript that described this work was rejected by several journal editors without peer review, thus providing further direct evidence for suppression of small-molecule therapeutics. Epidemiologic study of death statistics in the VAERS database showed that 19,710 people lost their lives after COVID-19 vaccination; mortality from all other common vaccines does not sum to even 20% of this staggering value. The vaccine has also been responsible for significant morbidity. A consensus has begun to develop among physicians and scientists that COVID-19 disease and vaccination both result in chronic symptoms in many people, now called “Long COVID” or “Long-hauler’s syndrome”. Thus, vaccination does not appear to be a reasonable approach to combat COVID-19 disease. In view of this, development, testing, and approval or repurposing of therapeutics is imperative, especially as we observe recent increases in mortality due to COVID-19 Omicron XBB.1.5. Chlorpheniramine maleate, an over-the-counter medication, is uniquely positioned to serve as a broad-spectrum antiviral against SARS-CoV-2 and other viruses in this post- pandemic age.
Tom Boom
Department of Science and Engineering, University College Roosevelt, P.O. Box 94, 4330 AB Middelburg, The Netherlands.
Anna Budinská
Department of Science and Engineering, University College Roosevelt, P.O. Box 94, 4330 AB Middelburg, The Netherlands.
Júlia Šeligová
Department of Science and Engineering, University College Roosevelt, P.O. Box 94, 4330 AB Middelburg, The Netherlands.
Ger T. Rijkers
Department of Science and Engineering, University College Roosevelt, P.O. Box 94, 4330 AB Middelburg, The Netherlands.
Abstract
Streptococcus pneumoniae is a polysaccharide encapsulated bacterium responsible for the majority of cases of community acquired pneumonia. The upper respiratory tract of children becomes colonized with pneumococci early in life, from the first weeks of life up to 18 months. Factors which influence timing of colonization include geographical localization, socio-economic circumstances, and household conditions.
Pneumococcal pneumonia to a degree is a seasonal disease, peaking in the winter months. One of the epidemiological determinants is that viral infections (in particular influenza) predispose for pneumococcal pneumonia. The infectious nature of pneumococcal pneumonia was underscored during the COVID-19 pandemic. Due to societal restrictions imposed (face masks, social distancing) the incidence of invasive pneumococcal disease (IPD) dropped, and returned to pre-COVID-19 numbers after lifting of the restrictions.
There are 100 different S. pneumoniae serotypes, based on differences in the capsular polysaccharide. Introduction of protein conjugated polysaccharide vaccines (PCV) has reduced the incidence of IPD in children. Because children are the reservoir for other risk groups, in particular the elderly, introduction of PCV has indirectly also reduced the burden of IPD in latter risk group. The first generation of PCV consisted of the seven most prevalent pneumococcal serotypes. After implementation, replacement colonization of the upper respiratory tract with non-vaccine serotypes was observed and also replacement disease. Upcoming 24-valent PCVs will have a much broader coverage, but whether replacement disease now has been eliminated remains to be seen.
Dr. Sridevi Kulkarni
Senior Resident, Dept of Community Medicine, BGS Global Institute of Medical Sciences, Bangalore
Dr. Guruckeeran Nakkeeran
Non-Pg Registrar, Critical care Medicine, CMC Vellore, Bangalore
Mr. Narayana Swamy DM
Assistant Professor- statistician, Dept of Community Medicine, ESIC Medical College PGIMSR, Bangalore
Dr. Govind GS
Tutor, Department of Physiology, BGS GIMS, Bangalore
Dr. Rani HL
House- surgeon, BGS GIMS, Bangalore
Abstract
Introduction: The novel coronavirus disease (COVID-19) pandemic, is a newly emergent disease and its epidemiology was unknown. In absence of effective treatment and vaccines, prevention of spread was the only option to save mankind. Social distancing, diseased isolation, and face mask use were initiated across the globe as prevention strategies. Of these, using face masks has stood as time tested strategy. But the introduction of face masks in Indian settings, without prior education on appropriate methods of use (wear, storage, disposal) has made their effectiveness questionable. Hence, the present study intended to assess the knowledge, attitude, and practice of face mask use among rural adults and to address the gaps if any.
Objectives:
- To determine the prevalence of face mask usage
- To determine the prevalence of practicing appropriate method (WHO recommended) of face mask use.
- To assess knowledge, attitude, and practice of face mask use and factors influencing them.
Methodology: A community-based cross-sectional study was conducted in the rural field practice area of BGS Global Institute of Medical Sciences, Bangalore. Pretested questionnaire was administered to 120 participants through the face-to-face interview. There were 8,5 and 11 questions used to assess knowledge, attitude, and practice of face mask use respectively.
Results: The face mask acceptance rate was 98.6%. Only 1/3rd of the study population knew the appropriate method (WHO) of wearing a face mask. The majority of participants had good knowledge (76.6%) and positive attitude (74.9%) towards mask use, but poor practices (76.6%). Knowledge about face mask use was associated with age, education, and occupation. A positive attitude towards mask use was associated with the participants’ education level. Whereas the practices related to face mask use was poor and was not associated with any of the factors mentioned above.
Conclusion: The media (mass/social) has equipped people with good knowledge about face masks and the current pandemic has brought in a positive attitude. But people lack skills in appropriate mask use, storage, and disposal. Community activities directed towards Behavioural Change Communication are the need of the hour to ensure WHO-recommended practices for face mask use and disposal.
Ken Steven Rosenthal & Daniel H Zimmerman
CEL-SCI Corporation, 8229 Boone Blvd, Vienna, VA 22182, USA
Abstract
Autoimmune disease disrupts the normal immunological balance by promoting a perpetual cycle of innate/immune/inflammatory responses that continues due to the continued presence of antigen. The disease cycle is in turn amplified and regulated by cycles of antigen-specific T cell mediated immune responses. Removal of the stimuli or regulation of the disease drivers can stop the cycle to allow rebalancing and prevent the progression or chronicity of disease. As an alternative to the current treatments for autoimmune and inflammatory disease, which reduce, inhibit or eliminate the triggers, drivers or antigens, newer approaches stimulate regulatory responses, or inhibit or repurpose the effector/inflammatory responses to control the immune disease cycle. LEAPS (Ligand Epitope Antigen Presentation System) therapeutic vaccines for rheumatoid arthritis are presented as examples of therapies that elicit antigen-specific T cell modulation of autoimmune and inflammatory responses to treat disease.
Poy Theprungsirikul, MD
Clinical Fellow, Yale School of Medicine, Yale University, New Haven, CT, USA
Natalia Neparidze, MD
Associate Professor of Internal Medicine (Hematology); Research Leader, Myeloma Program, Hematology, Yale School of Medicine, Yale University, New Haven, CT, USA
Abstract
Cancer has been recognized as one of the major comorbidities associated with severe outcomes in the novel coronavirus disease 19 (COVID-19) patients. Compared to those with solid tumors and those without cancer, patients with hematologic malignancies appear to have more severe clinical outcomes and higher rate of mortality from COVID-19. This was particularly demonstrated during the early pandemic period. The COVID-19 pandemic has posed additional challenges in the management of hematologic malignancies, including establishing prompt diagnoses, providing optimal treatment while minimizing the risk and sequela of COVID-19 infection. Given these challenges, clinical practice guidelines and recommendations on management of hematologic malignancies during the COVID-19 pandemic were developed and proposed based on expert panels and individual expert opinions. Multiple myeloma is the second most common hematologic malignancy. The management of patients with multiple myeloma during the COVID-19 pandemic is extremely challenging as patients with multiple myeloma are particularly vulnerable to infections due to underlying humoral and cellular immune dysfunction, cytotoxic chemotherapy, immunotherapy, cellular therapy and steroid regimens, advanced age, and the presence of other comorbidities. In this paper, we attempt to provide a general review of clinical practice management patterns during and after the COVID-19 pandemic in patients with multiple myeloma and demonstrate how changes evolved as more knowledge was gained over time. Specifically, we review the impact of the pandemic on treatment approaches, supportive care, and vaccinations for patients with newly diagnosed multiple myeloma, relapsed/refractory multiple myeloma, patients with stable disease, and those with precursor states like monoclonal gammopathy and smoldering multiple myeloma. During early pandemic several changes were noted in myeloma care including minor delay in time to treatment initiation and tendency to defer autologous stem cell transplant. However, after 2022, with the advent of effective vaccines and treatment strategies the severity of COVID-19 infection decreased and care of myeloma returned to usual management, incorporating transplant, CART and multiple novel immune therapy approaches. Finally, we highlight the importance of meticulous vaccination schedule for patients with myeloma for all common viral, bacterial pathogens and vaccination against COVID-19.
Rohan S. Kulkarni, MBBS, MS
Dr. DY Patil Medical College, Hospital & Research Centre, Pimpri, Pune, India.
Salva G. Ahmed, MD
Brookville Family Care, Premier Health Family Medicine, Brookeville, Ohio, USA.
Sunil S. Kulkarni, PhD, MBA, CFA
Department of Engineering Management, Systems, and Technology, School of Engineering, University of Dayton, Ohio, USA.
Virendra K. Bhojwani, PhD
Department of Mechanical Engineering, MIT Art, Design and Technology University, Pune, India.
Abstract
Background: As of March 2024, the populations of the USA, India, and Brazil have suffered over 2.4M combined COVID-19 deaths and are ranked as the top three countries in the world with the most fatalities due to the virus. Their populations differ significantly regarding their races/ethnicities, population densities, urbanization proportions, GDPs (Gross Domestic Products), age profiles, and COVID vaccinations. However, surprisingly they are bunched up at the top when it comes to the world’s COVID-19 deaths.
Aims: This paper examines these populations, with a combined 194M infections and counting, to provide a comprehensive understanding and explore the social inferences of the virus.
The main objectives of this study are to comprehend similarities and differences of the three populations for race, age, income, population density, urbanization, and effectiveness of the COVID-19 vaccines.
Methods: To understand COVID-19’s underlying deaths in a country, its demographic and economic data were analyzed.
Results: For the US, in terms of population proportion of a race, the Whites saw a higher percentage of COVID-19 deaths, while the Blacks’ deaths were in line with this proportion but both the Hispanics and Asians saw lower COVID-caused deaths than their proportions. For the country, 90% of these deaths were for the ages of over 55 years. Surprisingly the 0-17 years age group saw only 0.15% of total 1.2M COVID-19 deaths.
Brazil did experience the second highest COVID-19 deaths in the world. 80% of these deaths occurred in 11 states out of the country’s 26. The same states have 70% of Brazil’s population creating 65% of the country’s GDP.
India, the world’s most populated country, experienced the third-highest COVID-19 deaths in the world. 87% of its COVID deaths came from 14 states out of the country’s 28. These states have 85% of India’s population produced 89% of the country’s GDP. India’s top five COVID-caused deaths producing states experienced 60% of these deaths.
Conclusions: The top five COVID-19 deaths-producing states for both the USA and Brazil were driven by population and GDP rankings. A blend of GDP, total population, urbanization, and median age were key drivers for India’s COVID-19 deaths.
Ali Zare Dehnavi
Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine and Science, Rochester, USA; Research Center for Antibiotic Stewardship and Antimicrobial Resistance, Infectious diseases department, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
Seyed Ali Dehghan Manshadi
Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High-Risk Behaviors, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
Seyed Ahmad Seyed Alinaghi
Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High-Risk Behaviors, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
Behnam Amini
Research Center for Antibiotic Stewardship and Antimicrobial Resistance, Infectious diseases department, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
Fatemeh Rashidi
Research Center for Antibiotic Stewardship and Antimicrobial Resistance, Infectious diseases department, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
Masoumeh Farrokh Ashtiani
Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High-Risk Behaviors, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
Hoda khoshnevis
Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High-Risk Behaviors, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
Adel Tabrizi Tochaee
Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High-Risk Behaviors, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
Mohammadreza Salehi
Research Center for Antibiotic Stewardship and Antimicrobial Resistance, Infectious diseases department, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
Cristina Mussini
University of Modena and Reggio Emilia, Modena, Italy
Abstract
There is limited information about COVID-19 vaccines in people living with HIV (PLWH). We aimed to compare the immunogenicity and effectiveness of the Sinopharm BIBP COVID-19 inactivated vaccine between PLWH and non-HIV individuals in the Omicron era. We evaluated the production of receptor-binding domain (RBD), spike, SARS-CoV-2 IgG, and neutralizing antibodies in both PLWH (case) and individuals without HIV (control) groups three months after they received the second dose of the vaccine. All participants were also followed during three months after the second dose for the COVID-19 infection and its outcomes (hospital admission, need to intensive care unit, and mortality). A total of 250 individuals comprising 150 PLWH and 100 people without HIV were recruited. The mean age was 42.2 years. The infection rate was significantly higher in non-HIV individuals than in PLWH (63% vs. 21.3%, p < 0.001). The hospitalization rate in the PLWH group was significantly hig1her than that in the non-HIV group (5.3% vs. 1%, p = 0.009). There were no significant differences in the mean levels of Spike antibody (84.4 ± 34.4 vs. 95 ± 109.5 RU/mL), RBD antibody (65.6 ± 42 vs. 69 ± 42.3 RU/mL), and SARS-CoV-2 IgG (2.9 ± 2.5 vs. 3 ± 2.3 Index) between the groups. The mean value of neutralizing antibodies was significantly higher in non-HIV individuals (34 ± 23.3 vs. 26.2 ± 20 µg/mL, p = 0.005). The Sinopharm BIBP COVID-19 inactivated vaccine can be as immunogenic in PLWH as in non-HIV individuals. This vaccine is likely more effective in preventing Omicron-associated hospitalization in non-HIV individuals.
Wen-Jan Tuan, DHA
Departments of Family and Community Medicine and Public Health Science, College of Medicine, Pennsylvania State University
Adriana Von Rago
College of Medicine, Pennsylvania State University, Pennsylvania, USA
Christopher Heron, MD
Department of Family and Community Medicine, College of Medicine, Pennsylvania State University, Pennsylvania, USA
Michael Partin, MD
Department of Family and Community Medicine, College of Medicine, Pennsylvania State University, Pennsylvania, USA
Kyle Burke, MD
Departments of Family and Community Medicine, Pennsylvania State University, Pennsylvania, USA
Grace Hwang
Aleksandra E. Zgierska, MD, PhD
Abstract
Despite advancements in vaccines and treatments for COVID-19 over time, many concerns remain about reinfection and waning immunity against COVID-19 and its variants, including among individuals treated with stimulants. The study aimed to evaluate the risk of COVID-19 reinfection and severe illness among adults prescribed stimulants compared to those not on stimulant therapy to elucidate the potential relationship of this therapy to the COVID-19 reinfection-related outcomes. A retrospective cohort study was conducted using the TriNetX database consisting of over 2,563,130 adults (age ≥18 years) with COVID-19 infection from January 1, 2020 to April 30, 2022. COVID-19 reinfection was defined as a new COVID-19 illness documented ≥ 30 days after the initial infection. Logistic regression was applied to assess the odds ratios (ORs) of COVID-19 reinfection and severe illness course (presence of emergence department (ED), hospitalization, and intensive care unit (ICU) care, mortality) within 30 days of reinfection, controlled for demographic and comorbid condition characteristics. Analysis revealed that adults who received at least three prescriptions for stimulants, compared to those without any stimulant prescriptions within six months prior to the initial COVID-19 illness, were more likely to be re-infected by COVID-19 (aOR=1.36, 95% confidence interval (CI): 1.32-1.41), but less likely to be treated in the ED (aOR=0.77, 95% CI: 0.72-0.82), hospital (aOR=0.72, 95% CI: 0.63-0.82), ICU (aOR=0.68, 95% CI: 0.53-0.89), or die (aOR=0.31, 95% CI: 0.15-0.64) within 30 days of reinfection (all p-values < 0.01). The study offers additional insights into the potential risks and benefits of prescription stimulants to aid in clinical decision making for treating COVID-19 reinfection in adults on stimulant therapy.
Dr. Úrsula Oswald-Spring, Prof
Regional Centre of Multidisciplinary Research at National Autonomous University of Mexico (CRIM-UNAM in Spanish)
Abstract
The objective of this article review the complex impacts of COVID-19 not only as a health problem, but also related to unemployment, poverty rise, gender violence, and climate disasters in Mexico. An open, dissipative, and self-regulating system methodology interlinks the complex socioeconomic, political, and sanitary feedback. Governmental and private corruption in the purchase of drugs, protective gear, badly equipped and unbuilt hospitals after the 2017 earthquakes, lack of trained personnel, and people with comorbidity produced excess mortality. Support from private hospitals, ventilators, medical specialists from Cuba, vaccines bought worldwide, and the immunization of 71.3% of the adult population in 2022, reduced dead and contagion. The socioeconomic and health impacts were wide, when in 2020 12.5 million people lost their jobs, mostly women and youth, poverty raised, and lockdown increased intrafamilial violence. Governance included direct money transfers to elderlies, students, youth in apprenticeship, single mothers, and peasants planting timber and fruit trees. The cash steered youth away from organised crime, granted food security, and the acquisition of protective gear. New public works created employment in the poorest southern regions highly affected by COVID-19 due to undernourishment, improving their livelihood. Further, 52 cyclones on both oceans, forced people to flee, while the Trump Administration declared Art. 42 and returned migrants from different countries to the Mexican border, increasing the contagion. The Biden Administration gave vaccine gifts against COVID-19 to stimulate export industries in the northern region. The Russian-Ukrainian war raised prices that affected the food security of poor people. Agreements with supermarkets and food providers, systematic increases in the minimum wage, and new public infrastructure enhanced jobs, improved livelihood, and alleviate poverty. A rigorous macroeconomic policy allowed free vaccination also for children over five years and the building of an alternative public health system, providing sanitary and preventive medical attention to the impoverished population in the indigenous southern regions.
Amofah George, MPH
President, Ghana Public Health Association
Badu Sarkodie
Sarkodie Badu (Former Director Public Health, Ghana Health Service)
Abstract
The Ghana Public Health Association organized a scientific seminar in April 2014 to examine the introduction of genetically modified organisms (GMOs) into public use, and their potential health consequences. The seminar was driven by the current public debate on the subject. Concerns have been raised about the use of GMOs, especially in developing countries, for a variety of reasons including ethical and biosafety considerations. The seminar identified some of their advantages such as the introduction of pest-resistant, disease-resistant, and drought-tolerant crops; the potential for reduced use of chemicals and pesticides; improvement the nutritional properties of crops, and huge potential for the production of pharmaceuticals and vaccines.
Potential health concerns raised included current efforts focusing primarily on a few crop/trait combinations of high commercial value; most trial designs are laboratory design and of short duration; increasing observation of trends in organ disease with the use of GMOs, and lack of labeling of GMO products that hinder post-marketing surveillance.
There is the need to enhance local capacity to research the introduction and use of GMOs; to put in place appropriate regulatory mechanisms including, particularly, the labeling of their products, and long-term post-marketing surveillance for possible negative health consequences.
Furthermore, the appropriate state agency should put in place advocacy and communication strategies to keep the public informed about the health and other consequences of GMOs, for informed public choices.
Willem van Aardt, BProc (Cum Laude), LLM (UP), LLD (NWU)
North-West University, Research Unit: Law, Justice and Sustainability, Potchefstroom Campus, South Africa
Abstract
The global fervor to develop and deliver a vaccine to protect people against COVID-19, the disease caused by SARS-CoV-2, has been extraordinary. COVID-19 vaccine development has been pursued at an unprecedented speed and scale; following the Emergency Use Authorization (EUA) of COVID-19 vaccines, rapid mass vaccination deployment efforts commenced in all earnest. This fervor to get a needle into every arm has now led to the European Commission president calling on the EU’s 27 member states to consider mandatory vaccination across Europe. With an intensification in COVID-19 vaccine hesitancy and many refusing to be vaccinated, an important question that arises is whether obligatory COVID-19 vaccination policies are ethical and legal in terms of international human rights norms and standards. Article 4(2) of the International Covenant on Civil and Political Rights which was ratified by 173 States Parties worldwide enumerates a specific list of human rights from which no derogation is allowed even in times of a public emergency. Included in this list of non-derogable rights is a sub-category of internationally recognized human rights known as “physical integrity rights” that includes the right to be free from medical or scientific experimentation. International human rights law is unambiguous that all people should be afforded their non-derogable fundamental human right to free and informed consent. Normative ethical perspectives and legal obligations erga omnes dictate that States Parties should not make COVID-19 vaccination mandatory in breach of International Human Rights Law relating to non-derogable rights that are regarded as core human rights, jus cogens. A bioethics perspective, rooted in fundamental human rights, should play a crucial role in the COVID-19 pandemic.
Shalom Onyinye Katas, MD
School of Medicine, International University of the Health Sciences (IUHS) Basseterre, St. Kitts & Nevis
Inelefo Roger Iyayi, MD
Department of Medicine and Surgery, University of Benin, Edo State, Nigeria
Princess Okoronkwo, PharmD
Department of Pharmacy, D’youville University, Buffalo, NY
Derek Olatunde Olagbemi, MBBS, LMCC
College of Medicine, University of Lagos, Lagos, Nigeria
Tinuade Oladayo Adeakin-Dada, MD, LMCC, PGCertCR
Department of Medicine, Windsor University School of Medicine, St Kitts and Nevis
Oluwadamilola Daniel Odutola, MD
Department of Internal Medicine Medical University of South Carolina, SC, USA
Paul Akhere Momodu
Department of Medicine, International University of the Health Sciences Basseterre, St Kitts and Nevis
Stephen N. Utulor, MD
Department of Medicine, International University of the Health Sciences (IUHS) School of Medicine, Basseterre, St Kitts and Nevis
Uzodinma Joseph Nwadinigwe, MBBS
Department of Medicine, University of Nigeria Teaching Hospital Ituku, Nigeria
Oluwabusayo Monsurat Osundiji, MD
Department of Medicine, St Martinus University, Curacao, Netherland Antilles
Okelue E. Okobi, MD
Department of Family Medicine, Larkin Community Hospital (PSC), Miami, FL, USA
Abstract
Background: Diabetes mellitus is a prevalent chronic disease that significantly increases the risk of complications from infections such as influenza and pneumococcal disease. Despite established recommendations for vaccination, coverage rates among adults with diabetes remain suboptimal. This study aims to analyze trends in influenza and pneumococcal vaccination rates among adults with diabetes using the United States Diabetes Surveillance System (USDSS) database.
Methods: This retrospective database study utilized data from the USDSS from 2000 to 2022, which provides comprehensive nationwide data on diabetes care. The study population included adults aged 18 and above with a documented diagnosis of diabetes. Data were extracted on demographic variables (age, sex, race/ethnicity), clinical characteristics (type of diabetes, duration of diabetes, comorbid conditions), and vaccination records. Descriptive statistics summarized demographic and clinical characteristics, while temporal trends in vaccination rates were analyzed using graphical representations.
Results: Over the past two decades, influenza vaccination rates among adults with diabetes increased from 41.4% in 2000 to 56.7% in 2019, reflecting improved awareness and healthcare practices, though slightly dipping to 54.2% in 2022. In contrast, pneumococcal vaccination rates showed more variability, starting at 29.3% in 2000, peaking at 39.4% in 2018, and declining to 30.2% in 2022, indicating challenges in maintaining high coverage. Influenza vaccination rates showed an overall increasing trend across all demographic groups: rates among Hispanic individuals increased from 32.1% in 2000 to 55.4% in 2022, non-Hispanic Whites from 43.4% to 52.7%, and non-Hispanic Blacks from 39.2% to 44.5%. Pneumococcal vaccination rates also increased but displayed more variability; Hispanic rates peaked at 33.3% in 2016, non-Hispanic Whites at 45.6% in 2019, and non-Hispanic Blacks at 41.7% in 2017. Higher educational attainment was consistently associated with higher vaccination rates for both vaccines.
Conclusions: This study highlights significant improvements in influenza and pneumococcal vaccination rates among adults with diabetes over the past two decades. However, disparities remain, particularly among racial and educational groups. Targeted strategies are necessary to address these disparities and enhance vaccination coverage, ultimately reducing the risk of severe infections in this vulnerable population.
Robert G. Lisziewicz
VERDI Solutions; Vienna, Austria
Felipe Oviedo
Microsoft AI for Good Research Laboratory; Redmond, USA
Andras G. Szasz
VERDI Solutions; Vienna, Austria
Juan L. Ferres
Microsoft AI for Good Research Laboratory; Redmond, USA
Franco Lori
VERDI Solutions; Vienna, Austria/ Research Institute for Genetic and Human Therapy; Milano, Italy
Julianna Lisziewicz
VERDI Solutions, GMBH
Abstract
Background: The COVID-19 pandemic has necessitated the development of efficient diagnostic tools to predict T-cell responses, which are crucial for viral clearance and protection against reinfection. Current diagnostic tests lack the ability to predict the epitope repertoire of an individual that induces T-cell responses.
Methods: We developed VERDI, a new machine learning-based diagnostic tool that leverages the sequence data of all the six HLA class I alleles of an individual to rank all putative epitopes based on their potential to induce T-cell responses. VERDI was trained on a comprehensive clinical dataset of 920 SARS-CoV-2 epitopes and validated using an independent dataset collected for the FDA-approved T-detect COVID test. We compared VERDI’s performance with existing HLA-allele-based models through statistical analyses.
Results: Our findings reveal that VERDI’s top-ranked epitopes accurately represent the individual’s epitope repertoire that participates in T-cell responses. VERDI outperformed current models, improving T-cell response prediction recall by threefold and precision by eightfold. It exhibited exceptional diagnostic accuracy, precision, and recall in predicting the potency of the top 20 epitopes. Despite experimental limitations that allow testing of only 1% of putative epitopes, VERDI accurately predicted 30% of these, implying a potentially higher accuracy if broader testing were feasible. Notably, the mean potency of the top-ranked epitopes predicted by VERDI, which reflects the strength of an individual’s SARS-CoV-2-specific T-cell responses, exhibited a Gaussian distribution.
Conclusions: VERDI is the first diagnostic tool that uses the complete HLA genotype data to predict the breadth and strength of an individual’s T-cell responses to SARS-CoV-2 infection. Its ability to accurately identify the potency of epitopes involved in individual T-cell responses and its superior performance compared to the state-of-the-art make it a new resource for personalized vaccine design and disease management.
Kunal Saha, MD, PhD, Ex-professor
Dept. of Pediatrics & Microbiology, Ohio State University Medical Center and Children’s Hospital, Columbus, Ohio, USA and President, People for Better Treatment (PBT), Commercial Point (Ground Floor), 79 Lenin Sarani, Kolkata, India.
Abstract
COVID-19 pandemic has devastated the world over the past three years with millions already dead. Despite making major strides to combat the pandemic with useful vaccines against the SARS-CoV-2 virus, potential for more dangers from new variants of COVID-19 cannot be ruled out. Several studies have recently shown that the number of COVID-19 deaths as reported by different nations was far less than the number of people who may have died due to pandemic. Although many countries across the globe may have undercounted the death toll due to COVID-19, India holds the ignominious distinction for the highest number of unrecognized COVID-19 deaths. Both unreliable science and willful spread of misinformation about true lethal nature of COVID-19 by devious governmental authorities are likely responsible for the gross underreporting of COVID-19 deaths. Complete scientific transparency and absolute immunity against political intrusion of healthcare would be essential to end the COVID-19 pandemic and to protect humanity against other pandemics in future.
Challenges and Opportunities in Skin Cancer
Special Issue:
Challenges and Opportunities in Skin Cancer
C DeGiovanni
Department of Dermatology, University Hospitals Sussex NHS Foundation Trust. Brighton General Hospital, Elm Grove, Brighton, BN2 3EW. United Kingdom
M Patel
Department of Dermatology, University Hospitals Sussex NHS Foundation Trust. Brighton General Hospital, Elm Grove, Brighton, BN2 3EW. United Kingdom
P Drake
Department of Dermatology, University Hospitals Sussex NHS Foundation Trust. Brighton General Hospital, Elm Grove, Brighton, BN2 3EW. United Kingdom
P Sains
SainsSurgical. 4 Elsworthy, Thames Ditton, Surrey, KT7 0YP
V Sridhar
Osney thermo-fluids Laboratory, Department of Engineering Science, University of Oxford. Oxford. OX1 3PJ
Kam Chana
Osney thermo-fluids Laboratory, Department of Engineering Science, University of Oxford. Oxford. OX1 3PJ
Abstract
Skin cancer is one of the most common cancers in the world. Skin cancer is currently a global public health problem that is escalating. In the UK, the incidence of malignant melanoma has increased from 837 per year to 6963 per year in males and 1609 per year to 6952 per year in females between 1981 and 2018. Early diagnosis and treatment, as with any other disease will have a positive outcome in terms of survival and costs of management. Advances in technology have allowed the development of tools that provide rapid and sensitive diagnosis of many diseases. This paper describes the development and use of a thermal based technique which directly measures the thermal properties of skin. The Thermal Product Sensor (TPS), a new biosensor, has been demonstrated in the diagnosis of skin malignancies. The technique is quantitative and is shown to distinguish between normal and malignant skin. The study demonstrates on 12 patients the thermal product technique successfully detected skin cancers in comparison to normal skin.
Hamza Malick, BS
Texas A&M College of Medicine, Dallas, Texas
Seo Won Cho, BS
Texas A&M College of Medicine, Dallas, Texas
Kyle C. Lauck, MD
Baylor University Medical Center, Dallas, Texas
Aaisha Firdaus, MBBS
Katihar Medical College & Hospital, Katihar, Bihar, India
Dario Kivelevitch
Texas A&M College of Medicine, Dallas, Texas; Baylor University Medical Center, Dallas, Texas
Abstract
Psoriasis, a chronic immune-mediated skin disorder impacting millions globally, is increasingly recognized for its links to various disease processes. As our understanding of immune dysregulation in psoriasis progresses, acknowledging the pivotal role of dysregulated T-cells in the pathogenic development of the persistent inflammatory state becomes crucial. This immune dysregulation and the resulting prevalent inflammatory state have raised concerns about psoriasis potentially serving as a significant comorbidity in cancer development among patients. To contribute to this discussion, we conducted a global retrospective cohort study with propensity score matching (PSM) using the TriNetX Analytics platform. The study aimed to investigate whether patients diagnosed with psoriasis face an elevated risk in the development of cutaneous malignancies, encompassing both melanoma and non-melanoma skin cancers. Our findings confirmed a noteworthy concern, revealing a significantly increased risk of developing cutaneous neoplasms in individuals with psoriasis. In conclusion, our study underscores the importance of heightened awareness and the necessity for routine skin cancer screenings in this unique patient population. The observed association between psoriasis and an increased risk of cutaneous neoplasms highlights the need for proactive medical interventions and emphasizes the potential impact of psoriasis as a comorbidity in the context of cancer development.
Chase Paulson
University of Utah School of Medicine, School of Medicine, Salt Lake City, UT
D James Barker
University of Utah School of Medicine, School of Medicine, Salt Lake City, UT
Christian Pompoco
Moran Eye Center, Salt Lake City, UT
Sam Taylor
University of Utah School of Medicine, School of Medicine, Salt Lake City, UT
Matthew Conley
University of Utah School of Medicine, School of Medicine, Salt Lake City, UT
Ayesha Patil
Moran Eye Center, Salt Lake City, UT
Nnana Amakiri
Moran Eye Center, Salt Lake City, UT
Brian Stagg
Moran Eye Center, Salt Lake City, UT
Robert Ritch
Einhorn Clinical Research, Department of New York Eye and Ear Infirmary of Mount Sinai, New York, New York
Jae H Kang
Brigham and Women's Hospital, Channing Division of Network Medicine, Boston, MA
Janey L Wiggs
Mass Eye and Ear, Boston, MA
Karen Curtin
University of Utah School of Medicine, School of Medicine, Salt Lake City, UT; Moran Eye Center, Salt Lake City, UT
Barbara Wirostko
Moran Eye Center, Salt Lake City, UT
Abstract
Background: Prior data suggest an association between non-melanoma skin cancer, i.e., basal and squamous cell cancers most often located in areas of sun exposure, and pseudoexfoliation syndrome. This study aimed to evaluate the association between these conditions and UV exposure through a detailed questionnaire in a large and robust Utah population.
Methods: The two arms of this study are a population-based study (evaluated via chart review) and a UV exposure study (evaluated via a questionnaire). Participants answered a questionnaire designed to assess lifelong UV exposure, including leisure and occupational sun exposure, likelihood to tan or burn in early life, eye and hair color, smoking behavior, vitamin D deficiency, skin cancer history, alcohol consumption, and caffeine intake.
Conclusion: Descriptive findings suggest UV exposure over an adult’s lifespan may associate with a higher risk of non-melanoma skin cancer in Utah exfoliation patients vs. unaffected individuals. Patients with exfoliation glaucoma reside at higher elevations than non-glaucoma patients.
Keywords: Non-Melanoma Skin Carcinomas, Non-Melanoma Skin Carcinomas and UV Exposure, Exfoliation Syndrome, Exfoliation Syndrome in Utah
Yunfeng Zhao
Department of Pharmacology, Toxicology & Neuroscience, LSU Health Sciences Center in Shreveport, Shreveport, LA 71130, USA
Annapoorna Sreedhar
Department of Pharmacology, Toxicology & Neuroscience, LSU Health Sciences Center in Shreveport, Shreveport, LA 71130, USA
Chunjing Zhang
Department of Pharmacology, Toxicology & Neuroscience, LSU Health Sciences Center in Shreveport, Shreveport, LA 71130, USA; School of Basic Medicine, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, China
Noel Jacquet
Department of Pharmacology, Toxicology & Neuroscience, LSU Health Sciences Center in Shreveport, Shreveport, LA 71130, USA
Abstract
Upregulation of uncoupling protein 2 (UCP2) is considered a prosurvival mechanism for cancer cells. This prosurvival function is thought to be mediated by UCP2’s uncoupling activity which reduces the production of superoxide in the mitochondria. However, exactly how highly expressed UCP2 regulates cell proliferation, cell cycle, and cell death during the early stage of tumorigenesis has not been studied thoroughly. For this purpose, we generated UCP2 stably overexpressed JB6 Cl-41 cells (a skin cell transformation model) and performed studies to answer the above questions. Our results demonstrated that UCP2 overexpression enhanced cell proliferation, activation of the oncoprotein Fra-1, anchorage-independent growth, 3D spheroids growth, and glucose uptake during skin cell transformation. Next, our results demonstrated that UCP2 overexpression resulted in marked decreases in the proportion of the cells in the G1 phase and an increase of cells in the S phase of the cell cycle, which was accompanied by increased expression of Cyclin E and Cdk2. Lastly, UCP2 overexpression did not enhance or suppress apoptosis during skin cell transformation, as indicated by Annexin V and active caspase 3/7 staining. Taken together, these data suggest that UCP2 upregulation mainly enhances the Fra-1 oncogenic pathway which drives cell proliferation, without inhibiting apoptosis during skin cell transformation.
David John Mackay Smith
University of Queensland
Abstract
Approximately 10% of genes oscillate according to a circadian clock. Even though cells are capable of independent oscillation there is a master controller in the brain, the suprachiasmatic nucleus (SCN), that provides a coordinated response throughout the body, influenced by daily and seasonal patterns of light and heat. These genes have widely varied functions but are significantly influential in DNA damage repair, the cell cycle, cellular proliferation and apoptosis, as well as metabolic function. Normal circadian rhythms are essential for the body’s natural defence against disease and cancer. Deregulation may enhance the capacity for carcinogenesis in the skin and the influence of the circadian clock helps explain two of the anomalies of melanoma exposure patterns: A higher incidence amongst indoor as opposed to outdoor workers and on intermittently as opposed chronically exposed skin.
Paul J. Davis, M.D.
Department of Medicine, Albany Medical College, Albany, NY USA; NanoPharmaceuticals LLC, Troy, NY USA.
Aleck Hercbergs
Department of Radiation Oncology, The Cleveland Clinic, Cleveland, OH USA.
Hung-Yun Lin
PhD Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
Matthew Leinung
Department of Medicine, Albany Medical College, Albany, NY USA; 2NanoPharmaceuticals LLC, Troy, NY USA.
Shaker A. Mousa
NanoPharmaceuticals LLC, Troy, NY USA; Vascular Vision Company, Troy, NY.
Abstract
Thyroid hormone as L-thyroxine (T4) at physiological concentrations acts at its cell surface receptor on integrin avb3 to stimulate cancer cell proliferation1. These proliferation studies have been conducted in vitro, but pharmacological reduction of T4 and substitution of nuclear receptor ligand 3,3’,5-triiodo-L-thyronine (T3) is a state of euthyroid hypothyroxinemia that has been shown clinically to arrest tumor growth in patients with cancer. T3 is inactive at physiological levels at the plasma membrane integrin receptor. A preclinical study of human basal cell carcinoma (BCC) cells has shown that the integrin thyroid hormone receptor regulates BCC radiosensitivity. While the large majority of BCCs are very manageable clinically, a small number of such tumors are aggressive. In this review of documented and proposed effects of T4 on BCC cells, we raise the possibility that BCC aggressiveness reflects T4 actions on its thyrointegrin target. The functions affected by T4 at the integrin in other human cancers include enhanced cell proliferation, anti-apoptosis, immune checkpoint regulation and metastasis, as well as state of radiosensitivity. The importance of investigating this possible pathophysiology is that euthyroid hypothyroxinemia may be tested as a treatment option.
The Skin Cancer Paradox
Joseph C. DiNardo
MS Toxicologist
Abstract
Although the safety and efficacy of ultraviolet filters (sunscreens) is widely accepted by consumers and medical professionals, the scientific community has yet to validate this conclusion. This is evident based on multiple literature searches obtained from PubMed, Google Scholar, ScienceDirect, ResearchGate, sunscreen manufacturers and dermatologic organization websites. In the absences of definitive data, industry continues to promote the use of these products to prevent cancers, specifically a 40% reduction in squamous cell carcinoma and a 50% reduction in melanoma based on one confounded non-reproduced study with numerous design flaws. This causes consumers to be misinformed leading them to intentionally increase ultraviolet light exposure, increasing their risk of skin cancers. Until the scientific community can clearly demonstrate that these products reduce/eliminate skin cancers, consumers should follow sun avoidance measures.
David John Mackay Smith
University of Queensland, St Lucia QLD 4072, Australia
Abstract
Public health messages clearly state the risks of solar radiation and how the risk can be mitigated. This is supported by the availability of creams that effectively block out the ultraviolet component of solar radiation. Why then does the incidence of skin cancer and particularly melanoma remain so disturbingly high in Caucasian populations?
Almost all organisms on the planet have had to adapt to the presence of solar radiation since the beginning of evolutionary time. There are beneficial effects as well as risks in exposure, not the least of which is that it is the ultimate energy source for living species.
We need to re-examine attitudes and exposure patterns with an appreciation that some exposure is essential for good health. A balance needs to be found between benefits and risks. This can only be done by understanding that there are a range of wavelengths of light with different effects rather than a focus solely on the adverse effects of the ultraviolet component.
Norman A. Brooks, M.D.
Institution: Skin Cancer Medical Center
Abstract
The majority of physicians treating melanoma in situ recommend a 5mm to 1cm margin with excision into the subcutaneous tissue extending between the superficial and the deep fat. There is always the potential for an unrecognized invasive component in a melanoma in situ, making aqueous zinc chloride solution an ideal agent to treat the excision wound of a melanoma in situ of the trunk and extremities. Zinc chloride solution penetrates deeply and widely, killing and fixing tissue when applied to the excision wound, facilitating the excision by allowing for a simple saucerized excision with a narrower and thinner margin while ensuring the treatment of any possible unrecognized invasive components. Zinc chloride has been used in a paste since 1835 to treat skin cancers and melanoma but unlike pastes zinc chloride in solution is recognized by the U.S. Food & Drug Administration as a generally safe substance (Code of Federal Regulations Title 21 [Part 182]). The solution penetrates as deeply and widely and effectively as in the paste which Mohs described to be an inactive vehicle for the active ingredient, zinc chloride solution. Mohs reported a large significant survival benefit (p=0.003) for invasive melanoma using surgery combined with zinc chloride over conventional melanoma surgery. Zinc chloride solution without the paste is a new medicine effective as a surgical adjuvant in the treatment of the excision wound of a melanoma in situ of the trunk and extremities. Zinc chloride can be used as a surgical adjuvant for any melanoma, but melanoma in situ of the trunk and extremities is the logical starting point for a physician interested in using this adjuvant in the treatment of melanoma. Zinc chloride is very powerful and potentially scarring and should be used on the excision wound of a previously histologically diagnosed melanoma only.
David John Mackay Smith
University of Queensland, Brisbane, Australia.
Abstract
The keratinocyte and the melanocyte, the main cellular constituents of the epidermis, are two very different cell types. Despite their different origins and functionality, they come together in the skin, synergistically, to function as a unit to control the adverse effects of solar exposure. The most significant element in this protective process is the ability of the melanocyte to produce melanin. This pigmented polymer is responsible for constitutive skin colour that plays a part in our identity as human individuals but more importantly, provides a tanning response. A change in pigmentation that provides both an immediate and prolonged protective effect from the damaging components of solar radiation.
The melanocortin 1 receptor, a cell surface receptor on the melanocyte, receives paracrine stimulation in the form of hormonal communication from the keratinocyte, initiating a series of intracellular molecular interactions in the melanocyte, eventually involving transcription factors in the nucleus, most notably the microphthalmia-associated transcription factor, resulting in upregulation of enzymatic production of melanin and finally, its transfer back to the keratinocyte.
The melanocortin 1 receptor is highly polymorphic and unfortunately this results in the Caucasians’ having constitutionally fairer skin combined with an incomplete tanning response, resulting in a higher susceptibility to skin cancer.
The melanocyte is a relatively long-lived cell and over its extended life span can accumulate a series of mutational events. With malignant transition to melanoma this oncogenic baggage, when combined with antiapoptotic machinery that helps melanocyte survival, resulting in relatively rapid progression of the malignant process and contributing to its resistance to therapeutics.
Natasha Boyette
Ernest Mario School of Pharmacy, Rutgers, the State University of New Jersey, Piscataway, NJ
Ava Dalton
Ernest Mario School of Pharmacy, Rutgers, the State University of New Jersey, Piscataway, NJ
Yearam Tak
Ernest Mario School of Pharmacy, Rutgers, the State University of New Jersey, Piscataway, NJ
Sophie Kang
Ernest Mario School of Pharmacy, Rutgers, the State University of New Jersey, Piscataway, NJ
Subbu Apparsundaram
Cellix Biosciences, Inc., Newark, New Jersey; Cellix Bio Private Limited, Hyderabad, India
Mahesh Kandula
Cellix Biosciences, Inc., Newark, New Jersey; Cellix Bio Private Limited, Hyderabad, India
John York
Ernest Mario School of Pharmacy, Rutgers, the State University of New Jersey, Piscataway, NJ; Institute for the Global Entrepreneur at the Rady School of Management and the Jacobs School of Engineering, University of California, San Diego, CA
Abstract
Introduction: Capecitabine is an oral prodrug of 5-FU, which interpatient pharmacokinetic (PK) variability related to liver function and severe adverse events (e.g., hand-foot syndrome, myelosuppression, and neurotoxicity) limits. CLX-155 is a novel oral 5’-DFCR prodrug involving 5’-DFCR as an intermediate for generating 5-FU, unlike capecitabine, which the liver does not metabolize. This study addresses the following research question: what is the activity of CLX-155 in a human colon cancer xenograft model in nude mice?
Methods: This study involved 50 Foxn1 athymic nude female mice implanted with the human colon cancer cell line HCT116 (5 million cells per site). Investigators randomized animals into five treatment groups (N = 10): vehicle control, CLX-155 at doses of 125, 250, and 500 mg/kg/day, or capecitabine 1000 mg/kg/day. Animals received oral treatment once daily for five days a week with two days off for a total of three consecutive weeks. Investigators evaluated treatment toxicity based on body weight loss. Calculations for tumor growth inhibition involved comparing changes in tumor volume on a given day to tumor volumes on Day 1.
Results: CLX-155 demonstrated statistically significant, dose-dependent tumor growth inhibition at all doses compared to vehicle control (p<0.0001). Tumor growth inhibition at Day 15 for CLX-155 treatment groups of 125, 250, and 500 mg/kg/day was 57.8%, 70.4%, and 90.6% respectively. Two animals in the CLX-155 500 mg/kg/day treatment group experienced complete tumor regression, and all animals in the CLX-155 treatment groups survived. Two animals in the CLX-155 250 and 500 mg/kg/day dosing groups experienced a decrease in body weight. In contrast, two mice in the capecitabine group exhibited clinical signs of hunchback and scaly skin, progressive weight loss, and eventual death.
Conclusion: CLX-155 demonstrated comparable tumor growth inhibition to capecitabine but at a lower dose, suggesting increased potency. In addition, CLX-155 exhibited improved tolerability and fewer adverse effects. These promising results support further investigation in Phase 1 clinical trials for managing colon cancer.
Haruo Sugiyama
Department of Cancer Immunology, Osaka University Graduate School of Medicine.
Abstract
Wilms’ tumor gene 1 (WT1) overexpresses in almost all kinds of hematological malignancies and solid tumors (hereinafter referred to as cancer). Therefore, WT1 protein is a ubiquitous tumor-associated antigen (TAA). Many clinical studies of WT1-targeted cancer immunotherapies (hereinafter referred to as WT1 cancer vaccine), including WT1 peptide vaccine, WT1 peptide-pulsed dendritic cell (WT1-DC) vaccine, and WT1 mRNA-electroporated dendritic cell (WT1 mRNA-DC) vaccine had been conducted for the treatment of almost all kinds of cancer. The clinical effect was promising, whereas the major side effects were the temporary fever and skin reaction on the vaccine injection sites and not significant. The appropriate combination therapy of WT1 cancer vaccine and chemotherapy enhanced WT1 immune response against cancer. Gemcitabine (GEM), for example, increased WT1 immune response through the promotion of the expression of WT1 antigen protein and HLA class I/II molecules in cancer. Furthermore, WT1 cancer vaccine immediately after hematopoietic stem cell transplantation (HSCT) induced sufficient WT1 immune response regardless of severe immunocompromised conditions and exerted sufficient clinical effect, suggesting that the immune condition immediately after HSCT should be suitable for the priming of WT1 immune response. Moreover, the combination therapy of WT1 cancer vaccine and immune checkpoint inhibitors (ICIs) was promising. Compared to the other TAAs, WT1 is especially unique in that it expresses not only in cancer cells but also in their stem cells at the quiescent state of cell-cycle, which are resistant to chemo-and radio-therapies. This uniqueness of WT1 largely contributes to cure cancer through the complete eradication of WT1-expressing cancer stem cells by WT1 immune response against them. Since the complete eradication of cancer stem cells is essential to cure cancer, and since only immune cells against cancer are considered to be able to kill the cancer stem cells at the quiescent state of cell-cycle, the introduction of immunotherapy, especially of WT1 cancer vaccine with sufficient safety is essential in the cure-oriented treatments of cancer. Accumulated clinical results suggest that WT1 cancer vaccine should be useful for cancer prevention, and the development of WT1 cancer prevention vaccine is awaited.
Challenges and Opportunities in Internal Medicine
Challenges and Opportunities in Internal Medicine
Chun-Man Chen
Yen-Ling Chen
Shu-Min Lin
Huang-Pin Wu
Jiun-Nong Lin
Kai-Huang Lin
Chin-Ming Chen
Kuang-Yao Yang
Shih-Chi Ku
Fu-Tsai Chung
Chih-His Kuo
Chien Tung Chiu
Chi-Kuei Hsu
Hsin-Hui Hsu
Chien-Ming Chu
Han-Chung Hu
Chung-Shu Lee
Shin-Hwar Wu
I-Chieh Mao
Ting-Yu Chao
Yi-Wen Chu
Du-Shieng Chien
Abstract
The relationship between serum selenium levels and mortality was investigated in septic patients with severe selenium deficiency (baseline selenium ≤ 80 ng/mL). Eligible patients of sepsis or septic shock were randomized to receive Placebo or High-Dose Selenium (1,000 μg/day) via intravenous injection. Safety, serum selenium, mortality, SOFA, and Glasgow Coma Scale (GCS) scores were monitored. Among all 330 subjects, 27.9% subjects (n=92) had severe selenium deficiency (mean serum selenium = 66.5 ng/mL). Mortality of severe selenium deficiency patients was 27.2%, significantly higher than 17.9% of all subjects. In severe selenium deficiency Placebo group (n=45), 62% subjects showed gradual increase of selenium levels to ~110 ng/mL (mortality ~21.4%), while 38% subjects remained at low selenium ≤ 110 ng/mL throughout study (mortality ~41.2%). Mortality for Placebo subjects with normal baseline selenium ≥ 110 ng/mL was 13.6%. With High-Dose Selenium treatment, 91% of severe selenium deficiency subjects showed quick selenium increase to ~110 ng/mL (mortality 25.5%). Mortality was reduced to 8.6% for High-Dose Selenium subjects with baseline selenium ≥ 110 ng/mL. The odds ratio showed significantly greater survival of High-Dose Selenium subjects with baseline selenium ≥ 110 ng/mL (91.4%) than severe selenium deficiency Placebo subjects (74.1%). Mean baseline SOFA scores for severe selenium deficiency patients were 9.1–9.4, decrease of SOFA scores in High-Dose Selenium subjects was significantly greater than Placebo subjects, along with significant improvement of GCS scores. Repeated infusion of High-Dose Selenium in severe selenium deficiency patients for 14 days was safe and well-tolerated. Mortality for patients with sepsis was clearly affected by serum selenium concentrations. High mortality (41–50%) was observed in the sepsis patients constantly with low selenium £ 80 ng/mL; mortality was reduced to 21–23% if their serum selenium could be increased to ≥ 110 ng/mL. High-Dose Selenium resulted in rapid restoration of serum selenium and improved the survival of severe selenium deficiency septic patients. Low mortality (9–14%) was observed in the sepsis patients starting with baseline selenium ≥ 110 ng/mL. Overall this study demonstrates the significant impact of insufficient selenium levels on the mortality of septic patients. Treatment with high-dose selenium reduced the mortality of severe selenium deficiency septic subjects.
Wajid Ali Rafai
Ahmad Ussaid
Babar Riaz
Faisal Amin Baig
Sohail Anwar
Atif Masood
Rahma Fiaz
Khurram Saleem
Farrukh Iqbal
Abstract
SARS-COV-2 emerged as pneumonia of unknown etiology and transforming into global pandemic leading mass casualties globally. It leads to serious complications with a wide range of symptoms and laboratory and radiological abnormalities.
Methodology: This retrospective study included 191 admitted patients was conducted between 15 April 2020 and 31 August 2020 at university of Lahore teaching hospital, Lahore, Pakistan. Baseline demographics, clinical, laboratory and radiological characteristics were compared amongst disease severity categories with One way ANOVA and comparison amongst recovered and non-recovered was carried out by independent t test, Fisher’s exact and chi-square test respectively. All data were analysed in SPSS 25 and p-value <0.05 was considered significant.
Results: Out of 191 patients enrolled in this study, majority were male and above 50 year age. Fever (68%) was the most common symptom though dyspnea was statistically significant (p-value<0.05) and diabetes (41.4%) being the most common comorbidity. A statistical significant downtrend in eosinophil counts were observed in critical and severe disease from non-severe disease and similar trend was observed in non-recovered (died) patients than recovered. A significant rise in neutrophil to lymphocyte ratio, crp, ferritin and d-dimer were observed amongst critical and severe disease and non-recovered patients (p-value<0.05). Patients with eosinopenia had low survival proportion at day 5 and 10 than those with relatively normal eosinophil counts.
Conclusion: Patients with advanced age, multiple comorbidities, elevated hematological, deranged coagulation markers presented with more severe disease and had poor outcome. In particular, eosinopenia can play key role in early diagnosis, disease severity recognition and disease surveillance as it is an independent risk factor for prognosis.
Preeti Malik, MD, MPH
Azka Zergham, MBBS
Neel Patel, MBBS
Yasameen Kerakhan, MBBS
Shamima Somi, MD
Nagaraj Sanchitha Honganur, MBBS
Aelia Akbar, MD, MPH
Aran Deol, MD
Richa Jaiswal, MD
Janice L. Gabrilove, MD, FACP
Urvish Patel, MD, MPH
Abstract
Background and Objective: Few small observational studies have described various therapeutic interventions utilized in coronavirus disease 2019 (COVID-19) patients based on single/multi-center experiences across the globe. Understanding the utilization of available and possible treatments to curb the COVID-19 pandemic is paramount. We aimed to identify the prevalence and disease-associated utilization of specific therapeutic reagents in hospitalized COVID-19 patients as a function of severity status.
Methods: In systematic review and meta-analysis, extracted data on treatments utilized and severity of COVID-19 hospitalized patients from observational studies using PRISMA guidelines from December 1, 2019 to August 20, 2020. The pooled prevalence and odds of treatment utilization were obtained, and created forest plots using random‐effects models.
Results: 29 studies with 8570 COVID-19-positive patients were included. Higher odds of the utilization of steroids (pooled OR:4.47; 95%CI:3.18–6.28; p<0.00001), antibiotics (3.1;1.81–5.30; p<0.0001), and IV Immunoglobulin (IVIG) (3.76;2.11–6.72; p<0.00001) was observed in patients with severe disease. No association of remdesivir (initially administered via clinical trials and subsequently FDA-approved during this study period), lopinavir/ritonavir, or hydroxychloroquine (HCQ) treatment with the severity of disease was observed.
Conclusion: Higher utilization of steroids, lopinavir/ritonavir, antibiotics, hydroxychloroquine (HCQ), and IV Immunoglobulin (IVIG) was observed in severe COVID-19 patients. Due to limited studies on remdesivir, its accurate utilization could not be delineated. Currently, no Level A evidence favoring single-drug treatment for COVID-19 exists, and trials are needed of combination therapy to evaluate efficacy on the survival outcome.
Ammouri W
Harmouche H
Khibri Hajar
Maamar Mouna
Mezalek Tazi Zoubida
Adnaoui Mohamed
Abstract
Macrophage activation syndrome can be primary with a genetic etiology, or secondary, associated with malignancies, infections or systemic diseases. Its a severe and potentially life-threatening complication of autoimmune diseases. The incidence of MAS among patients with systemic lupus erythematosus is not well known, as most of the previous studies were limited to a small number of case series or case reports. In recent years it has been suggested that macrophage activation syndrome in systemic lupus erythemaosus may be underrecognized because it can mimic the clinical features of the underlying disease or be confused with an infectious complication. The diagnosis of macrophage activation sydrome in adults is supported by hyperferritinemia (higher than 2000 ng/ml), and/or splenomegaly, pronounced cytopenias, hypofibrinogenemia, characteristic cytokine profile and hypertriglyceridemia. In the case of systemic lupus erythematosus flare, hyerferritinemia is the strongest indicator to differentiate them from MAS. So far, no validated and universally embraced diagnostic criteria for macrophage activation syndrome in adult secondary to systemic lupus erythematosus are available. It is important to know the parameters that can guide the clinician towards the diagnosis of macrophage activation syndrome in adult with systemic lupus. Early diagnosis and intensive therapy are essential in improving clinical outcomes. Hence, we decided to write this mini- review to focus on the demographic data, on the pathophysiological mechanisms, clinical and laboratory manifestations, treatments, and outcomes of patients with systemic lupus erythematosus associated macrophage activation syndrome.
Panagiota Xaplanteri
http://orcid.org/0000-0002-4760-4165Vasileios Zoitopoulos
Vasiliki Diamanti
Athanasia Moutafidi
Panagiota Masoura
Charalampos Potsios
Konstantina Filioti
Angeliki Rapanou
Christina-Panagiota Koutsouri
Zoi Grammenidou
Aimilios Tzoudas
Chara Sakarelou
Tatiana Beqo Rokaj
Katerina Ntzinia
Elsa Kampos Martinez
Georgios Papachristopoulos
Constantinos A Letsas
Abstract
Background: Since December 2019 mankind is agonized over the deadly coronavirus disease 2019 (COVID-19) which is due to the novel coronavirus (2019-nCoV) or Severe Acute Respiratory Syndrome Coronavirus-2 (Sars-cov-2).
Methods: In this retrospective study, laboratory findings and demographic features form all confirmed COVID-19 patients who attended the Emergency Department of both branches of our hospital during the first semester of 2021 were collected and analyzed. The working hypothesis was that initial laboratory data at the time the patients seeked medical assistant for the first time, regardless of comorbidities and day of onset of symptoms, can help predict patients’ outcomes. Demographic data and laboratory tests were compared between hospitalized and non-hospitalized patients.
Results: Data of 270 patients were collected and analyzed retrospectively. 31 blood measurement parameters performed in both hospital branches were compared between hospitalized and non-hospitalized patients. Of those, WBC count (p=0.016), neutrophil percentage (p<0.001), lymphocyte percentage (p<0.001), platelet count (p=0.041), glucose (p<0.001), urea (p<0.001), creatinine (p<0.001), SGOT (p=0.024), CK (p<0.053), LDH (p<0.001), GGT (p<0.001), sodium (p<0.001), calcium (p<0.001), high sensitivity Troponin I (p<0.001), and ferritin levels (p<0.001), proved statistically significant. Regarding demographic data, age was significantly linked to patients’ survival.
Conclusion: Our data suggest that common initial laboratory findings of COVID-19 patients who seek for the first-time medical assistant regardless of comorbidities and time from onset of symptoms can give clues to the patient outcome. Age is also important for patients’ survival. Especially in a Primary Health Care Setting, common blood parameters like WBC count, neutrophil and lymphocyte percentage, platelet count, glucose, urea, creatinine, SGOT, CK, LDH, GGT, sodium, calcium, high sensitivity Troponin I, and ferritin levels, could be really helpful to predict disease severity.
Richard Z Cheng, MD, PhD
Michael Passwater
Tievi Yang, MD
Abstract
For over 3 years, the Covid-19 pandemic felt like a world war and has taken close to 7 million lives, disabled many more people, and caused innumerable economic losses around the globe. What can we learn from this tragedy? Are we ready for another Covid-19-like pandemic? Studies show that the majority of people with SARS-Cov-2 infection either show no symptoms or only mild to moderate clinical manifestations; only a small percentage develop severe Covid-19 disease, indicating that the clinical severity of Covid-19 disease is not determined only by the SARS-Cov-2 virus, but more importantly by how the host responds to the viral infection, what is known as natural immunity. Research of what enhances or weakens the natural immunity against viral infections and the practical application thereof is an important lesson one can learn from the pandemic. Research of natural immunity enhancing factors is summarized in this paper. One key characteristic of natural immunity against viral diseases is its non-specificity. The importance of this non-specificity helping to prevent and treat other infections of known or unknown viruses is also discussed. Calls for the clinical application of safe and inexpensive nutrients such as vitamin C in the prevention and treatment of Covid-19 have met significant resistance and objection from the medical authorities and the media since the pandemic outbreak. The main objection is the perceived lack of research and the absence of regulatory approvals. This raises a fundamental philosophical question: what is the primary goal of the medical profession? Facing a new viral pandemic like Covid-19 with no prior research, let alone any approved treatments, why is there opposition to known safe, inexpensive, widely available and often effective nutrients like vitamin C? Why are case reports and case series discounted or ignored rather than explored further to try to help more people? Is such objection protecting consumers or harming the public? Statistics show that viral epidemics and pandemics are occurring more frequently, with a recent review of epidemics and pandemics since 1600 concluding “ the yearly probability of occurrence of extreme epidemics can increase up to threefold in the coming decades.”1. When the next Covid-19-like pandemic of a new virus hits us, are we going to repeat the Covid-19 tragedy? Can improved emphasis on nutritional interventions to prepare for and respond to disease outbreaks mitigate future pandemics?
Aaron I. Vinik, M.D., Ph.D.
Etta J. Vinik, MEd.
Ying-Chuen Lai, M.D.
Steven Morrison, Ph.D.
Sheri R. Colberg, Ph.D.
Serina Neumann, Ph.D.
Joshua Edwards, MS.
Scott Gerwe, M.D
Carolina Casellini, M.D.
Henri Parson, Ph.D.
Abstract
Aims To explore the impact of the autonomic nervous system function in “disease-free” people for testing and appropriate therapies in different age-groups.
Methods Seventy-five disease-free volunteers who participated in a previous study were randomly selected from five age-groups (30-79 years) for a cross/sectional study to assess the impact of fatigue on cardiac/autonomic function by analysis of heart rate variability (HRV) and measures of cognitive and physical fatigue on quality-of-life-fatigue (QOLF) scores. Written informed consent was obtained and protocol approved. To induce fatigue, three 5-minute walking trials were performed on an instrumental treadmill, increasing the incline in increments of 2°/min to measure perceived exertion (RPE) at the beginning and end of each trial. Polar monitors measured heart rate (HR); a modified Borg 10-point scale measured RPE. Cardiac autonomic reflex tests (CART) with time/frequency domains analyzed HRV. QOLF scores were measured and analyzed for correlation with sympathetic/parasympathetic function on the Norfolk QOL-F fatigue scale.
Results QOL-F scores were not significantly different among 5 age groups, likely due to wide standard deviations and small subject numbers. Significant correlations between overall fatigue severity and several indices of HRV were found, independent of age, gender, and body mass index (p<0.05). Self-rated physical fatigue and compromised activities of daily living (ADLs) were related to sympathetic hyperactivity and autonomic imbalance (p=0.04). Participants in the (70–79-year-olds) category had impaired scores.
Conclusions The study identifies a relationship between autonomic nervous system function and cognitive and physical fatigue even in “disease-free” people in different age- groups and suggests that fatigue is impacted by somatic and autonomic nerve function. Higher self-ratings of perceived fatigue were associated with sympathovagal hyperactivity. Impaired HR response to exercise in older people corresponding with vagal over-activity, and paradoxically, best self-rated QOL-F, mandates clinical autonomic dysfunction testing and lifestyle therapies to prevent catastrophic events.
Mohammed Shaban
Franklin Sosa
Jose Lopez
Gustavo J. Duarte
Justin D. Mark
Asma Khizar
Swati Jain
Rishabh Mishra
Miguel Rodriguez Guerra
Timothy J Vittorio
Abstract
SARS-CoV-2 is a highly contagious viral illness that started the COVID-19 pandemic in March 2020. Accumulating evidence suggests that the cardiovascular system is primarily affected by SARS-CoV-2. Cardiovascular complications such as myocarditis, acute coronary syndrome, heart failure, arrhythmias, and venous thromboembolism have been reported. The role of cardiac biomarkers in diagnosing and monitoring COVID-19 patients is becoming of particular interest, as it may provide insights into the underlying mechanisms of cardiovascular injury and inform clinical decision-making.
Troponins, specifically troponin I, have been widely studied and was proven to be elevated in COVID-19 patients with myocardial injury, indicating a negative prognostic indicator and association with poorer outcomes. Elevated levels of Natriuretic peptides, such as B-type natriuretic peptide (BNP), have been noted in severe COVID-19 cases and are associated with higher mortality rates. However, it is essential to consider that elevated natriuretic peptide levels in COVID-19 patients may also be influenced by factors other than heart failure. CK-MB, a subtype of creatine kinase, has been found to have significantly higher concentrations in COVID-19 patients with high disease severity or non-survivor status, suggesting its potential as a biomarker for risk stratification in this population. Myoglobin and lactate dehydrogenase (LDH) are additional cardiac markers that can indicate heart muscle damage, but their specificity in COVID-19 patients may be limited.
The widely used cardiac markers provide valuable diagnostic and prognostic information about cardiac injury and function in COVID-19 patients. Still, their performance characteristics and interpretation should be considered in the context of the individual patient and conjunction with other clinical assessments.
Wen Liu
Mark Gonn
Susanna von Holst
Jessada Thutkawkorapin
Xiang Jiao
Jan Björk2
Ann-Sofie Backman
Kristina Lagerstedt-Robinson
Annika Lindblom
Abstract
Colorectal cancer (CRC) is a multifactorial disease, where both the environment and genetics play a role. It is estimated that approximately 35% of CRCs have a potentially identifiable genetic cause. Well-known and highly penetrant genetic causes make up less than 5% of all CRC, and leave many families not explained by known predisposing genes/mutations. Low penetrant alleles have also been thought to modify the risk of CRC. Linkage studies have been successful in discovering and localizing highly penetrant genes in CRC and risk loci has become possible to discover performing genome wide association studies (GWAS).
In this study we have analyzed families with CRC where individuals with CRC as well as individuals with premalignant lesions, adenomas, were codes as affected. In total 600 individuals in 121 families were included in the study.
In total three genomic regions were found with suggestive linkage located at 4p16.3, 6p24.3 and 10p14. These regions were further studied using sequencing analysis and association studies using haplotypes.
Amy J. Armstrong
Carolyn E. Hawley
Ya Su
Anat Marmor
Sigal Sviri
Isabella Schwartz
Shimon Siri
Zeev Meiner
Abstract
While COVID-19 has had a detrimental impact on most of the world’s population, it has especially affected health care workers (HCWs) who are on the front lines fighting the virus. How HCWs cope with the pandemic have recently been explored. Differences across cultural and health care system settings related to fear of COVID 19 and measures of wellbeing may provide further insight to the coping mechanisms and experiences of HCWs during this worldwide pandemic. The overall subjective well-being and meaning in life scores are noticeably higher for the American participants whereas the fear of COVID and resilience scores are close in both studies, with slightly higher resilience and lower fear in the Israeli HCWs. Age, ethnicity and lower resilience were found to be significantly associated with higher fear of COVID-19 in both cohorts. In the Israeli participants, education level and life satisfaction were also associated with lower fear of COVID19 whereas in the American cohort, gender and relationship were also associated. These results suggest that albeit the cultural differences, similar mechanisms namely age and resilience, are important in coping with fear of the COVID-19 pandemic among both cohorts of HCWs. Therefore, it is important to enhance resilience in order to reduce the psychological burden of the pandemic among HCWs. This study was conducted prior to the availability of a vaccine.
Ali Hamdan
Amir Omar
Rayane Salameh
Pierre Hani
Abstract
Cholangiocarcinoma, an adenocarcinoma arising from the epithelium of biliary ducts, is considered the second most common hepatic malignancy after hepatocellular carcinoma with increasing incidence over the past 3 decades. Many imaging modalities with correlation to clinical presentation are used for the diagnosis and staging of cholangiocarcinoma. However, the diagnosis of cholangiocarcinoma is still challenging due to the presence of some benign and malignant conditions that mimic the clinical presentation and radiological findings of this disease. One of those mimics is the condition of intrabiliary hydatid cyst rupture which can cause biliary obstructive symptoms over weeks with radiological findings that may be indistinguishable from those of cholangiocarcinoma and specifically klatskin tumor when found at the bifurcation of the common hepatic duct. In such a confusing situation, the correct preoperative diagnosis and potential treatment of the disease could both be made possible using Endoscopic Retrograde Cholangiopancreatography avoiding unrequired surgical interventions.
Survival Benefit of High Dose Versus Usual Dose of Baricitinib in Hospitalized Patients with COVID-19: A Systematic Review
Shihan Mahmud Redwanul Huq, Dr
Raziuddin Ahmed, Dr
Md Mahiuddin Ahmed, Dr Raihan Rabbani, Dr
Md Jahidul Hasan
Ahmad Mursel Anam, Dr
Abstract
Baricitinib is an oral selective Janus kinase 1 and 2 inhibitor with known anti-inflammatory and anti-viral properties. In patients hospitalized for coronavirus disease 2019 (COVID-19), baricitinib has shown to reduce the risk of death in line with dexamethasone and tocilizumab. However, the most effective and safe dose or optimal dose of baricitinib in severe COVID-19 was not addressed.
We conducted this systematic review to assess whether higher than usual dose could further improve survival as primary outcome. The need of ICU (Intensive care Unit) and Invasive or non-invasive positive pressure ventilation, time to wean from oxygen, length of stay at hospital and adverse events were analyzed as secondary outcome.
We included 10,032 patients in 5 studies (2 randomised control trials and 3 high quality clinical trials). Among them,5,071 patients received baricitinib at different dosage (4909 patients received 4 mg once daily and 162 patients got more than 4 mg daily) and 4961 received standard of care. Baseline characteristics including mean age, sex, co-morbidities, inflammatory marker (C-reactive protein/CRP) were similar across the intervention and standard care groups.
4 out of 5 trials showed significant survival benefit in baricitinib group usual to higher dose (4 to 8 mg daily). Use of higher dose in 3 controlled trials was associated with significant reduction in admission to ICU and requirement of invasive or non-invasive ventilation support, shortening of hospital stay and earlier stabilization of oxygen status which was not evident in two randomized control trials using usual dose (4 mg daily). There was no significant difference in any serious adverse events or opportunistic infections between higher dose versus usual dose group.
Therefore, baricitinib in higher dose could be a potent, highly effective and safe immunomodulatory drug in hospitalized patients with severe COVID-19.
Gustavo Alexis Lemus-Barrios
Jesus Beltrán España
Luisa Fernanda Rincón Benavides
Edward Andrés Cáceres Méndez
Angel Alberto García Peña
Abstract
Extended dual antithrombotic therapy, which entails the concurrent administration of acetylsalicylic acid and a P2Y12 inhibitor or anticoagulant beyond the initial 12 months of presenting with acute coronary syndrome, has been the subject of considerable research in recent years. The objective of this study was to evaluate the impact of dual antithrombotic therapy in stable coronary artery disease. We conducted a registered (PROSPERO CRD42023394771) assessing the safety and efficacy of antithrombotic therapy published over the past 20 years up to May 2021 in four databases (PubMed, EMBASE, BVSalud /LILACS, Cochrane Reviews). Using the RoB2 tool, we evaluated the risk of bias. We performed a literature search using keywords and identified 95 eligible articles, of which 23 were excluded as duplicates. After applying the inclusion and exclusion criteria, we found 29 articles for a detailed review and assessment of bias by applying the ROB2 toll, and we found that five articles had a low risk of bias. Our analysis found that extended dual antithrombotic therapy reduces ischemic cardiovascular outcomes, but it comes at the cost of an increased risk of bleeding when compared with acetylsalicylic acid monotherapy.
Neglected Tropical Diseases key aspects for the rheumatologist
Anouk Le Goueff
David Jayne
Charlotte Martin
Eric Hachulla
Frédéric Vandergheynst
Nicky Longley
Abstract
Neglected tropical diseases (NTDs) are a group of 20 infectious diseases that are no longer restricted to tropical regions and that will be increasingly encountered by physicians of the Northern hemisphere.
In this article, we review key aspects of tropical medicine relevant for rheumatologists or doctors working with autoimmune diseases or immunosuppressive drugs in order to be aware of NTDs, look out for them and prevent their complications.
The article addresses four main topics:
- eosinophilia workup,
- rheumatic presentations of NTDs, such as myositis or arthritis
- lupus, granulomatosis with polyangiitis or vasculitis mimickers, such Leishmaniasis, Leprosy or Human African Trypanosomiasis and
- screening before starting immunosuppression, including Strongyloidiasis and Chagas disease
With this review, we intend to raise awareness for NTDs amongst rheumatologists and internists working in the Northern hemisphere. NTDs should be considered and excluded in patients with relevant travelhistory or exposure in following situations:
- during the differential diagnosis of a suspected new autoimmune condition,
- in case of poor response or flare of symptoms on initiating immunosuppressive therapy,
- during systematic screening prior to starting immunosuppressive medication, along with blood born viruses and tuberculosis.
Amorn Sankhaanuruk, M.D.
http://orcid.org/0000-0002-6819-0280
Nuntana Kasitanon, M.D.
http://orcid.org/0000-0002-1150-6424
Worawit Louthrenoo, M.D.
Abstract
Background: Nowadays, we have standard treatment guidelines for lupus nephritis (LN), a substantial proportion of patients have LN flare. The aims here to determine the incidence of LN flare in patients who had renal complete remission (CR) after receiving induction therapy (IT) and to identify factors associated with renal flare after CR in clinical practice.
Methods: Retrospective analysis in a tertiary-level center for the clinical outcomes of patients who had first LN episode, achieved CR (24hr urine protein <0.5 gm/day with normal renal function) within 12 months after received IT and received the maintenance therapy (MT).
Results: Eighty-seven out of 548 patients (96.6% female with mean age 29.5±10.8 years) met the inclusion criteria. During 6.1±3.4 years of observation after CR, 42 (48.3%) patients had LN flare. The incidence ratio of LN flare was 10.9/100 patient-years. The mean time from CR to flare was 3.1 years. Using Cox-regression analysis, induction to remission therapy ≥6 months (OR=0.33, p=0.006), and using statins ≥9 months after reached CR (OR=0.44, p=0.032) had a lower incidence of LN flare, while age at onset of disease ≤20 years had a higher incidence of LN flare.
Conclusion: Despite achieving CR with standard treatment, almost half of the patients had an LN flare within a few years. Young SLE patients had an increased incidence of LN flare, the long period of induction therapy and using statins may retard a flare of the disease.
Challenges and Opportunities in Neonatology
Challenges and Opportunities in Neonatology
Basil O. Ibe
Division of Neonatology, Department of Pediatrics, The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA 90502
Mona Hanouni
Attending Neonatologist, Children’s Hospital of Los Angeles, Los Angeles, CA 90027
J Usha Raj
University of Illinois, Chicago, IL 60607
James Popoli
Division of Neonatology, Department of Pediatrics, The Lundquist Institute at Harbor-UCLA Medical Center
Steven Popoli
Division of Neonatology, Department of Pediatrics, The Lundquist Institute at Harbor-UCLA Medical Center
Abstract
The fetus is exposed to chronic low oxygen environment, which is a desirable physiological condition for fetal pulmonary development and hemodynamics. On the other hand, if the newborn is exposed to low oxygen levels, the blood vessels of the lung thicken and narrow due to overgrowth of the smooth muscle cells in the vessel walls, the baby remains blue, resulting in the condition known as persistent pulmonary hypertension of the newborn (PPHN). In the United States, PPHN occurs in 0.43-6.8 newborns per 1000 live births and is most common in term and near-term newborns. Despite the significant advances in management of newborn respiratory diseases, PPHN is still associated with a high morbidity and mortality, accounting for about 10-20% of neonatal mortality. The current mainstay of therapy for PPHN is mechanical ventilation, fluid therapy and use of anti-inflammatory agents for cardiovascular support. Correction of hemodynamic acid/base balance and oxygen supplementation are also commendable therapeutic interventions. New ideas in PPHN therapy should include incorporation of in vivo, ex vivo and in vitro studies on intracellular signaling pathways of pulmonary vascular development in the state of PPHN. These new ideas will entail studies of the cross talk between vasodilators and vasoconstrictors in perinatal pulmonary hemodynamics.
Aseel Alzaghoul, MD, PhD
Division of Social and Transcultural Psychiatry, McGill University, Montreal, Quebec H3A 1A2, Canada.
Rama Eloulabi
Department of Psychology, Western University, London, Ontario N6A 3K7, Canada.
Paniz Fotoohi
School of Kinesiology and Health Science, York University, Toronto, Ontario M3J 1P3, Canada.
Khalid Yunis, MD
Professor of Pediatrics Head Division of Neonatology, Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical center, Beirut, Lebanon
Hala Tamim, PhD
School of Kinesiology and Health Science, York University, Toronto, Ontario M3J 1P3, Canada.
Abstract
Introduction: The aim was to assess the prevalence and factors associated with fear of COVID-19 among Syrian refugee parents in Ontario, Canada.
Methods: A sample of 540 Syrian refugee parents who resettled in Ontario were interviewed between March 2021, and March 2022. The level of fear was measured using the Fear of COVID-19 scale. Multiple linear regression analysis was performed to assess the relationships between socio-demographic, migration, and health-related factors and fear of COVID-19.
Results: The mean (SD) score for the Fear of COVID-19 scale was 15.6 (6.02), and 15.4% of the participants were categorized as having high levels of Fear of COVID-19. Results of the multiple linear regression analysis showed that low self-rated English/French language ability was significantly associated with increased fear of COVID-19 (Adjβ=0.65, p=0.047). When compared to participants who do not need an interpreter, those who needed an interpreter, and were always provided with one, were at reduced fear of COVID-19 (Adjβ=-1.56, p=0.061). In addition, findings indicated that low self-perceived socioeconomic status, more years spent in Canada, living in a refugee camp, and poor self-rated mental health contributed significantly to elevated levels of fear of COVID-19.
Discussion: Targeted intervention and prevention strategies for reducing the fear of COVID-19 should be considered for the Syrian refugee population in Canada. Language ability is one of the factors related to increased fear of COVID-19, thus, providing information and interventions in different languages is essential for this population.
Corrado Moretti
Department of Pediatrics, Policlinico Umberto I, Sapienza University of Rome, Italy
Camilla Gizzi
Department of Neonatology and NICU, Sant’Eugenio Hospital – ASL RM 2, Rome, Italy
Caterina Silvia Barbara
Pediatric Intensive Care Unit, Department of Maternal Science, Policlinico Umberto I, Sapienza University of Rome, Italy
Nicola Pozzi
Neonatal Intensive Care Unit, Department of Maternal and Child Health, San Pio Hospital, Benevento, Italy
Fabio Midulla
Department of Maternal Science, Policlinico Umberto I, Sapienza University of Rome, Italy
Paola Cogo
Department of Medicine, University Hospital S.Maria della Misericordia, University of Udine, Italy
Abstract
Bronchiolitis is one of the most frequent acute diseases of the lower respiratory tract in infants worldwide, and Respiratory Syncytial Virus remains the most common and aggressive viral disease. The course of the disease is usually benign, but its severity may change by evolving into parenchymal disease. In the more severe cases, its clinical and radiological characteristics may be consistent with acute respiratory distress syndrome. Management of these cases includes admission to paediatric intensive care and invasive mechanical ventilation. This paper reviews the definition of paediatric and neonatal acute respiratory distress syndrome, which was primarily designed and validated for adults. The article investigates the pathophysiology of paediatric acute respiratory distress syndrome further, describing how damage to the alveolar-capillary units, surfactant inactivation and inflammation occurs. Mechanisms that contribute to acute lung injury, such as volutrauma, barotrauma, stress and strain, are illustrated in detail, and an overview of the strategies that may help minimize neonatal lung injury and optimize ventilatory support is provided. These strategies include lung-protective mechanical ventilation, surfactant treatment, inhaled nitric oxide, high frequency oscillatory ventilation, recruiting manoeuvres, prone position and neuromuscular blocking agents. The objective is to help clinicians understand the peculiar pathophysiology of severe bronchiolitis and so guide them in preventing or attenuating lung injury during treatment. As such, this paper aims to contribute to defining optimal treatment of severe cases of bronchiolitis.
Luca Brunelli
Division of Neonatology, Department of Pediatrics, Spencer Fox Eccles School of Medicine, University of Utah
Kee Chan
American College of Medical Genetics and Genomics
James Tabery
University of Utah, Department of Philosophy;
Warren Binford
University of Colorado, School of Medicine, CU Law School;
Amy Brower
American College of Medical Genetics and Genomics; Munroe-Meyer Institute, University of Nebraska Medical Center, Creighton University School of Medicine;
Abstract
The year 2023 marked the 60th anniversary of screening newborns in the United States for diseases that benefit from early identification and intervention. All around the world, the goal of NBS is to facilitate timely diagnosis and management to improve individual health outcomes in all newborns regardless of their place of birth, economic circumstances, ability to pay for treatment, and access to healthcare. Advances in technology to screen and treat disease have led to a rapid increase in the number of screened conditions, and innovations in genomics are expected to exponentially expand this number further. A system where all newborns are screened, coupled with rapid technological innovation, provides a unique opportunity to improve pediatric health outcomes and advance children’s rights, including the unique rights of sick and disabled children. This is especially timely as we approach the 100th anniversary of the 1924 Geneva Declaration of the Rights of the Child, which includes children’s right to healthcare, and the 1989 United Nations Convention on the Rights of the Child that expanded upon this aspect and affirmed each child’s right to the highest attainable standard of health. In this manuscript, we provide background on the evolving recognition of the rights of children and the foundational rights to healthcare and non-discrimination, provide two examples that highlight issues to access and equity in newborn screening that may limit a child’s right to healthcare and best possible outcomes, detail ways the current approach to newborn screening advances the rights of the child, and finally, propose that the incorporation of genomics into newborn screening presents a useful case study to recognize and uphold the rights of every child.
Ronaldo Afonso Torres
Faculty of Medicine, Governador Ozanan Coelho University Center (UNIFAGOC), Ubá, Minas Gerais, Brazil.
Tiago Ribeiro Torres
Faculty of Medicine, Federal University of Juiz de Fora, Minas Gerais, Brazil.
Abstract
Introduction: The diagnosis of congenital heart diseases is a challenge for pediatricians due to the diversity of clinical presentations and symptoms, just like several other diseases prevalent in the neonatal period. Often the diagnosis is established during the gestation period, sometimes the hypothesis is formulated by neonatal screening. However, several cases will require clinical suspicion from the pediatrician. Given the possibility of this diagnosis, the evaluation of the infant cardiologist is essential. Unfortunately, this professional is not always readily available. In the intensive care units, health professionals use heart rate, blood pressure, capillary refill, urinary output and acid-base balance for hemodynamic analysis. These data are significant, but nonspecific. Thus, functional echocardiography can improve hemodynamic evaluation with positive impact on diagnosis. Our objective was to conduct a retrospective analysis of hospitalizations in a Brazilian neonatal unit, with the goal of identifying the diagnoses of congenital heart diseases made by a researcher using functional echocardiography, from July 2015 to September 2017, having as inclusion criteria; clinical manifestations of distress or respiratory failure, characterized by tachypnea, signs of dyspnea, need for oxygen therapy or ventilatory support and/or hemodynamic instability, characterized by tachycardia, cyanosis, cold extremities, prolonged capillary filling time, fine pulses and/or hypotension, low urinary output. Results: During the 26 months of the study, 362 neonates were hospitalized. Of these, 223 were included in the research for presenting cardiorespiratory manifestations. We observed three cases of obstructive shock related to cardiac tamponade, 18 cases of congenital heart disease, five cases of hypertrophic myocardiopathy, seven cases of myocardial dysfunction not related to structural heart disease, 46 cases of neonatal persistent pulmonary hypertension and 27 cases of patent ductus arteriosus (six with hemodynamics repercussion).
Conclusions: The results showed functional and/or anatomical changes in 105 patients analyzed (46.7%), identified a diversity of structural cardiopathies, improved hemodynamic evaluation with impact on the therapeutic approach. While using functional echocardiography in neonates, clinicians should be aware that undiagnosed critical congenital heart defects can present during this period. They should acknowledge the limitations of skills, and it should not be used as a screening tool for diagnosing or excluding congenital heart defects. A patient with a suspected critical congenital heart defect should be quickly referred to a pediatric cardiologist, even if this implies out-of-hospital patient’s transportation. We assume that the systematic implementation of this technology by the medical team can improve diagnostic accuracy, which can positively impact the therapy used.
Challenges and Opportunities in Myocardial Infarction
Challenges and Opportunities in Myocardial Infarction
Angel Martin Castellanos
Abstract
Despite the impact of the COVID‑19 pandemic, myocardial infarction remains the leading cause of cardiovascular deaths in Europe. Body mass index (BMI)-defined obesity is a major risk factor for myocardial infarction. However, in the association of anthropometrics and myocardial infarction, the lack of balance between the simple body measurements when comparing healthy and unhealthy cases has demonstrated that affects the outcome. Thus, regardless of association strength of anthropometrics, other criteria to judge the biological causality must be investigated.
We aim to assess different studies worldwide to understand the key concepts to demonstrate association biases for anthropometrics when predicting myocardial infarction risk. In this approach, natural mathematical inequalities between simple measurements in healthy subjects were investigated. Weight, height, height/2, waist circumference and hip circumference mathematically represent absolute values that do not express mathematically equality for the true risk. That way, the mathematical concept of fraction or ratio in anthropometrics such as BMI, waist-to-hip ratio (WHR) or waist-to-height ratio (WHtR) plays an important role. Thus, some anthropometrics may be seen as confounding variables when measuring high-risk body composition. Weight is a confounding factor without indicating a high-risk body composition, meaning that BMI is not fully predictive. WHR is a confounding variable concerning waist and WHtR due to imbalances between the mean hip–waist and hip–height, respectively, which indicates a protective overestimation for hip concerning waist and height. Waist measure may be a confounding variable concerning WHtR due to an imbalance in the mean waist–height. This occurs if, and only if, WHtR risk cut-off is >0.5 and if height is ignored as volume factor, therefore creating an overestimation of risk for waist circumference in the tallest people and underestimation in the shortest. Mathematically/anthropometrically, only WHtR-associated risk above BMI, waist and WHR holds true while considering it as a relative risk volume linked to a causal pathway of higher cardiometabolic risk.
In conclusion, WHtR is the only metric that is directly associated to a risk volume and having more biological plausibility. It should be used to assess the anthropometrically-measured myocardial infarction risk, once the imbalances between measurements and association biases are recognised.
ngel Martin Castellanos
Abstract
Cardiovascular diseases, mainly myocardial infarction and stroke, are the leading cause of death globally. Therefore, epidemiological research seems necessary to prevent cardiovascular events and mortality. However, real-world data from obesity metrics has intrinsic limitations for the assessment of causality. Despite of historical studies showing that the body mass index (BMI), the waist-to-hip ratio (WHR) and the waist circumference (WC) have been associated with increased risk of myocardial infarction, they might not be accurate from a causal inference.
Our aim was to summarize historical and novel findings about obesity metrics and myocardial infarction to evidence causal association biases. Method: an epidemiological review study was conducted while being original research when adding new anthropometrics in study design. Mathematical inequalities between the simple body measurements in anthropometrically healthy adults were described. Mean values and cut-offs for classic and several newer anthropometric variables were established. Classic metrics, ratios between the means of the simple measurements, a modulus |x| as a result of subtracting some measurement means from others (e.g., mean fat free mass minus fat mass) and somatotype ratings were collated. Mathematically, a non-zero difference for each modulus |x| in any population study would indicate an unbalanced distribution of the measurements between groups being compared, and therefore, the risk exposure levels differing. Thus, when between-groups the high-risk body compositions and somatotype ratings differ, any metric-associated risk is biased from a causal inference. After investigating large epidemiological studies, the historical omission of key anthropometric variables is stated, and as being uncontrolled confounding factors distorted causal inferences. Therefore, a protective overestimate of fat free mass and hip circumference over fat mass and WC, respectively, always occurred. Similarly, when the waist-to-height ratio values of >0.5 are associated; a protective underestimate of height over WC occurs. Any metric-associated risk is biased if prediction is made from WC or technologically measured body compositions without accounting for relative risk volume measures. In conclusion, summarizing the historical and novel findings regarding risk prediction, BMI, WHR and WC alone show evidence of causal association biases because of high-risk body compositions and risk exposure levels always differ between the groups being compared.
False Positive Results on Dobutamine Stress Echocardiography: A New Marker of Risk for Ischemic Events
Lisa Ferraz, Andreia Fernandes, Ana Faustino, Simão Carvalho, Adriana Pacheco & Ana Neves
Abstract
Background: Although dobutamine stress echocardiography (DSE) has a high specificity, there is still a subset of patients with false positive tests (FP); whether these results have prognostic value remains unclear.
Aims: To identify the clinical and echocardiographic predictors of FP on DSE and to evaluate the prognostic impact of FP on DSE.
Methods: Retrospective study of 355 consecutive patients who underwent DSE for ischemia assessment over a one-year period: 134 (37,7%) women, 70,3 ± 0,57 years. Demographics, risk factors, clinical and laboratorial parameters and DSE variables were evaluated. Patients were divided into 2 groups regarding the presence (FP+) or the absence (FP0) of a FP result on DSE and a comparative analysis was performed to characterize the groups and identify potencial predictors of FP results. Patients were followed for 2 years to assess acute myocardial infarction, hospitalization for acute heart failure (HF) and mortality.
Results: The FP rate was 4,5%. Comparing to FP0, patients in group FP+ were younger, baseline wall motion abnormalities were more frequent, had higher mean blood pressure values at rest and at peak stage and more often hypertensive response. There were no significant differences regarding previous coronary artery disease, medication or complete left bundle branch block. By multivariate analysis, only mean blood pressure values at rest (OR 0,01; 95%CI 0,005-0,02; p=0,003) and at peak stage (OR 0,02; 95%CI 0,000-0,004; p=0,003) were independent predictors of FP. During follow-up was observed: acute myocardial infarction (FP+: 12,5% vs FP0: 1,8%, p=0,046), HF (FP+: 6,3% vs FP0: 11,5%, p=0,44) and mortality (FP+: 6,3% vs FP0: 6,2%, p=0,65). After adjustment for age, sex and comorbidities, there were no diferences between the groups regarding HF and mortality, but the group FP+ mantained a higher rate of acute myocardial infarction (OR 0,21; 95%CI 0,065-0,354; p=0,005).
Conclusion: A FP result on DSE was associated with higher mean blood pressure values during the test and with higher rates of acute myocardial infarction during follow-up. This result on DSE should therefore be faced as a risk marker for ischemic events and can identify patients that may benefit from aggressive risk factor control and careful clinical follow-up.
Angel Martin Castellanos
Abstract
Among the components of Life’s Essential 8, body mass index is the anthropometric used in the scoring algorithm of cardiovascular health. Concerning myocardial infarction, the waist-to-hip ratio may show more predictive value than body mass index, waist circumference, and waist-to-height ratio, and has showed a greater excess risk of myocardial infarction in women than in men. However, bias has occurred in global research because of inadequate comparisons with the high-risk body composition. Hence, cardiology may have been confused for a long time because bias-related errors were always overlooked. This situation occurred when risk association was distorted by over- or under-estimating some simple measurements over others. Our aim was to determine whether the historical risk associated with some anthropometrics might provide a bias in causal inferences. Our study design was a review on data of the body of literature. We created new anthropometric variables, which were always omitted in previous large studies. In most studies, mathematical inequalities between the simple measurements in anthropometrically healthy subjects were overlooked, including disparities between lean and fat masses. That way, in omitting the difference in means between the simple measurements of length and body mass components, association findings and causality cannot be assumed. No anthropometric will be equivalent for estimating the same high-risk body composition if the difference in means between the simple measurements present an unbalanced distribution, and besides, being associated as confounding factors. Therefore, after describing new anthropometric variables termed as “x” and demonstrating that the simple measurements showed means of differences differentially distributed between healthy and unhealthy cases worldwide, association biases for the body mass index, waist-to-hip ratio or waist circumference alone may be endorsed, indicating the importance of these results. From a new anthropometric perspective, the waist-to-height ratio may indicate the concrete volume of an abdominal three-dimensional disc in direct-inverse relationship with waist-body height without showing association biases. This index may represent a new construct by defining a risk abdominal volume and avoiding potential confounding factors. In a paradigm shift, only the waist-to-height ratio meets causality criteria as the optimal index to predict myocardial infarction risk and to promote cardiovascular health.
Akira T Kawaguchi
Tatsuhide Tanaka, PhD & Mariko Yamano, PhD
Hideaki Sumiyoshi, PhD, Yoshiyuki Yamada, MD, PhD & Gen T Kawaguchi, MD
Hiroaki Kitagishi, PhD
Jacob Bergsland, MD, PhD
Abstract
Objective: Effects of PEGylated-carboxyhemoglobin bovine (SG) infusion and carbon monoxide (CO) inhalation were compared in a rat model of myocardial infarction (MI).
Methods: Lewis rats with induced MI received either 10 mL/kg of SG or of saline (SL), or 400 ppm CO inhalation (CO) daily for 3 days, 4 doses in total. On the fourth day, all animals had left ventricular (LV) functions studied by pressure-volume relationship analyses or in-situ myocardial gene expression by polymerase-chain reaction (PCR).
Results: Both SG infusion and CO inhalation increased the arterial carboxyhemoglobin fraction to 10%, which decreased the total O2 content by 10% for 3 hours before returning to control level, except for the plasma hemoglobin (Hb) over 200 mg/dL 24 hours later, in SG rats. Four days after MI, the SL and CO rats had enhanced cardiac contraction and relaxation, while the SG rats had LV end-systolic pressure, and the isovolumic contraction as well as relaxation remained suppressed at the post-MI levels. PCR showed significant reductions in in-situ antioxidant transcriptional master regulator (Nrf2), its down-stream antioxidant response genes (Nqo-1), hypoxic signal transduction in SG compared to SL or CO rats with enhanced pro-inflammatory, pro-apoptotic genes, and myocardial damage. These cardiac indices were reversed 4 weeks after MI, when SG had less LV dilatation, dysfunction, and myoglobin loss than those with SL or CO.
Conclusion: The results suggest that repeated SG infusion, but not CO inhalation, generates less oxidative stress, reduces hypoxic responses, supports early hemodynamics, and alleviates cardiac compensation early after MI, resulting in attenuated LV dilatation, dysfunction, and myoglobin loss late after MI in this rat model.
Siddhartha Mani, MD(Medicine), DM(Cardiology)
Sujata Sen, DNB(Emergency Medicine)
Kaushik Nag, MD(Community Medicine)
Prof. Sobhan Biswas, MD(Medicine)
Abstract
Background: The occurrence of arrhythmias among acute coronary syndrome patients is very common. However, their diagnosis is not considered in contemporary acute coronary syndrome patients. This study investigates the incidence and types of arrhythsmias among acute coronary syndrome patients presenting to the emergency department, as well as their association with various factors and patient outcomes.
Methods: The current prospective observational study was conducted at a tertiary care center in Kolkata, India. Data were collected from 76 acute coronary syndrome patients admitted between October 2020 and May 2021 to the emergency department. Information was gathered through semi-structured interviews and relevant investigations.
Results: The majority of the patients were aged 61-70 years, with three fourth of the study population being male. The incidence of arrhythmia was diagnosed in 77.6% of the patients. The most common arrhythmias were sinus tachycardia, ventricular premature complex, atrial fibrillation, sinus bradycardia, and complete heart block. Arrhythmias were more prevalent among ST-elevation myocardial infarction (62.7%) and unstable angina (8.5%) patients. Patients with Left Ventricular Ejection Fraction ≤ 40% had a higher incidence of arrhythmias (93.5%). The mortality rate during hospital stay was 11.9% among acute coronary syndrome patients with arrhythmias, while all acute coronary syndrome patients without arrhythmia had a 100% survival rate.
Conclusion: This study highlights the incidence and types of arrhythmias in acute coronary syndrome patients presenting to the emergency department. It reveals a higher prevalence of arrhythmias in specific subgroups, such as patients with ST-elevation myocardial infarction and those with a reduction in left ventricular function. These findings contribute to our understanding of arrhythmias in acute coronary syndrome and their association with patient outcomes, emphasizing the importance of appropriate management and monitoring in this population.
Arthur J. Siegel, M.D.
Abstract
The COVID-19 pandemic has decreased life-expectancy in the United States in 2021, causing over one million deaths especially in elderly persons with medical co-morbidities. While now waning, this epidemic continues to cause more than 500 fatalities per week mostly in individuals over70 years of age who are unvaccinated. Since viral epidemics have been shown to increase mortality due to atherosclerotic coronary heart disease and low-dose aspirin has been shown to reduce first myocardial infarctions by 44%, we recommend consideration of expanding the use of aspirin for primary cardiovascular prevention to reduce the cardiac morbidity and excess mortality associated with COVID-19 infections. Such aspirin use may be seen as especially appropriate for vulnerable elderly persons who qualify for treatment with Paxlovid (ritonavir-boosted nirmatrelvir) but are currently excluded for such in primary prevention guidelines of subspecialty societies. The rationale for this approach is further supported by recent proof of concept that vaccination, an alternative intervention for primary cardiovascular prevention, reduces the excess mortality associated with COVID-19 infection.
Can greater use of aspirin for primary cardiovascular prevention mitigate the excess cardiac mortality associated with COVID-19 as shown with prior viral epidemics 1-3? Recommendations from the 2019 ACC/AHA and 2021 ESC guidelines currently advise limited aspirin use for primary prevention except in persons aged 40 to 59 years with elevated ASCVD risk scores (10-year risk ≥10%) and for those aged 60 to 69 years only with risk ≥20% in the context of no excess risk of bleeding (Figure 1) 4,5. These guidelines have been endorsed by the United States Preventive Services Task Force, which acknowledge that low-dose aspirin in the primary prevention setting reduces the risk of major atherosclerotic cardiovascular events including myocardial infarction and ischemic stroke offset by an increased risk of gastrointestinal bleeding 7,8. Currently endorsed guidelines specifically recommend against aspirin use in individuals at age 70 and beyond.
Abstract
Background: Although pancreaticoduodenectomy (PD) is safe when performed in high-volume hospitals, many patients in low-income countries cannot access these hospitals. Barbados is a small island that does not have a high-volume pancreatic center. We sought to document peri-operative outcomes when PD was performed in Barbados.
Methods: We carried out a retrospective cohort study of all consecutive patients who underwent PDs over from August 1, 2016 to October 30, 2022. Therapeutic outcomes, post-operative morbidity and mortality were evaluated. Statistical analyses were performed using SPSS ver 16.0.
Results: Six patients at a mean age of 54.8 years underwent PD (mean annual case volume of 1). Two patients underwent planned vein resections and reconstruction. In this subset, the mean operating time was 325 minutes (Range 300-250; Median 325; SD ±35.4), mean estimated blood loss was 825mls (Range 750-900; Median 825; SD±106.1), and the mean transfusion requirement was 1 unit of packed cells (Range 0-2; Median 1; SD±1.41).
In the four patients without vein resection, mean operating time was 308 minutes (Range 280-350; Median 300; SD±24.01), median blood loss was 575 ml (Range 150-900; Median 700; SD±320.6) and mean transfusion requirements were 0.5 units of packed cells (Range 0-2; Median 0; SD ±0.84).
The mean ICU stay was 2.17 days (Range 1-3; Median 2.5; SD±0.98), and the mean duration of hospitalization was 9.3 days (Range 7-11; Median 9.5; SD±1.37). There were no recorded peri-operative deaths, but there was 1 (17%) minor complication (delayed gastric emptying) and 1 (17%) major complication (myocardial infarction).
Conclusion: In Barbados, there are good peri-operative outcomes after PD despite the low volume and challenging healthcare environment. We believe that (1) surgeon experience (2) continuous adaptive hospital learning and (3) regular audit of hospital data are better indicators of PD quality than volume data alone.
Abstract
Coronary artery disease (CAD) is the number cause of death in the world. It is estimated that 50% of Americans will experience a cardiac event in their lifetime. The underlying pathology leading to coronary artery disease and its clinical manifestations, such as angina, myocardial infarction, and sudden death is coronary atherosclerosis. While the disease is not usually manifested clinically until the sixth or seventh decade, the underlying pathology is initiated as early as the second or third decade. Numerous randomized clinical trials have shown cardiac morbidity and mortality can be prevented by lowering the risk of known conventional risk factors for CAD such as decreasing plasma cholesterol or controlling hypertension. Secondary prevention of these conventional risk factors has been very effective; however, primary prevention has been shown to be even more effective. A major barrier to primary prevention is the lack of markers to detect among young asymptomatic individuals those at risk for CAD. The conventional risk factors are often not present until the sixth or seventh decade which could be late for primary prevention. Genetic predisposition accounts for 50% of the risk for CAD. Recently over 200 genetic risk variants predisposing to CAD have been discovered. Based on these variants, one can express the genetic risk for CAD in a single number referred to as the Polygenic Risk Score (PRS). The PRS has been evaluated in over one million individuals and shown that those with high genetic risk have the highest incidence of heart disease and can be reduced by 40-50%, utilizing drugs (statins and PCSK9 inhibitors) or lifestyle changes (favorable diet and increased exercise). The genetic risk for CAD is determined at conception and thus can be predicted anytime from birth onward. The PRS detection of young asymptomatic individuals based on the PRS enables one to implement early primary prevention. Adoption of the PRS to risk stratify for CAD could represent a paradigm shift in the prevention of this pandemic disease.
John T. Braggio
Abstract
The success of remote sensing methodology to accurately estimate ambient particulate matter (PM) on the earth’s surface has resulted in the increased use of aerosol optical depth (AOD) AOD-PM10, AOD-PM2.5, and AOD-PM1 concentration level fused surfaces in cardiovascular epidemiologic and hypothesis-testing of inflammatory physiologic studies. AOD-PM fused surfaces have served as proxies for ambient PM monitor measurements in economically developed and developing counties as well as in urban and rural areas. Since 2012, 45 published studies have evaluated the association between increased AOD-PM concentration level readings and adverse cardiovascular outcomes. Fifteen surveillance studies used inflammation as a descriptive physiologic mechanism and another 20 investigations used the inflammatory physiologic mechanism to explain how AOD-PM exposure changes the cardiovascular system. Among the remaining ten studies, nine mentioned another description and one referred to another explanation. Analyses of the published studies showed: 1) There was 81% agreement between AOD-PM2.5 readings and ambient PM2.5 monitor measurements. 2) Developing countries had higher AOD-PM2.5 readings than developed countries. 3) Descriptive physiologic inflammatory studies found positive associations between higher AOD-PM readings and more acute myocardial infarction, cardiovascular disease, and heart failure outcomes. 4) Higher AOD-PM readings were associated with abnormal blood glucose, c-reactive protein and lipids in studies that cited the inflammatory physiologic mechanism as an explanation. 5) The percentage of specific outcomes increased as the number of identified risk factors also went up only if the AOD-PM2.5 readings were higher and decreased if the AOD-PM2.5 readings were lower. 6) The inflammation description AOD-PM2.5 readings mean (43.4 μg/m3) did not differ from the inflammation explanation AOD-PM2.5 mean (32.0 μg/m3). Study results were used to update the physiologic inflammatory mechanism as a mediator of the effects of AOD-PM exposure on the cardiovascular system. The full extent of the adverse effects of AOD-PM exposure on the cardiovascular system only becomes evident when cardiovascular and other pathophysiological changes are also considered and evaluated. This review paper aims to demonstrate why AOD-PM and cardiovascular system studies are a new and useful source of information about how ambient PM exposure adversely impacts the cardiovascular system in diverse populations in different countries.
Ashish Vasudev, BSc (Hons), MBchB
Abdus Samee Wasim, BSc (Hons), MBBS, MRSC
Akash Sharma, FRCS(Tr&Orth)
Yuvraj Agrawal, FRCS(Tr&Orth)
Abstract
Hip and knee arthroplasty is an extremely successful and cost-effective procedure that is widely performed to restore function and alleviate pain. The arrival of the SARS-CoV-2 virus (COVID-19) brought significant disruptions to delivery of surgery worldwide, including lower limb arthroplasty. Three years on from the start of the pandemic the effects of the virus are still present. This literature review aims to explore current data published from our single specialty orthopaedic centre and data collected nationally and internationally, on the impact of the COVID-19 pandemic on lower limb arthroplasty.
Elective hip and knee arthroplasty in the UK fell by approximately 40% and 50% respectively (2020 vs 2019) and by the end of 2021 the number of procedures completed still remained below pre-pandemic levels. As a result, elective waiting times are longer than ever before, with more patients suffering worse health states and a significant impact on quality of life. The UK National Hip Fracture Database showed an active COVID-19 infection was associated with a three-fold greater risk of 30-day mortality post lower limb arthroplasty. Several reports have also correlated peri-operative COVID-19 infection with increased risk of systemic complications with the virus such as pneumonia, deep vein thrombosis, pulmonary embolisms, acute kidney injury and myocardial infarction to name a few.
NHS England provided guidelines for safe recommencement for elective operating. Upon adoption of these recommendations, several orthopaedic units found similar rates of post-operative complications and mortality to pre-pandemic levels, demonstrating that safe elective care can be delivered even during an emergency pandemic setting. The development of rapid testing, use of personal protective equipment and introduction of pre- and post-operative isolation protocols were effective measures to allow elective surgery to restart. For infected individuals awaiting surgery, delays of at least seven weeks are recommended to reduce complication rates. There is limited literature discussing the impact of the vaccine on post-operative complications and mortality. Early reports however have suggested vaccinated individuals benefit from a reduced mortality risk in emergency cases of hip fracture surgery, but this is an area which would benefit from further research.
Ovidiu Vasile Jimborean, Daniela Tatiana Sala, Cristian Borz, Marton Denes, Mara Andreea Vultur, Gabriela Jimborean & Radu Mircea Neagoe
Abstract
We analized the early and late postoperative complications that occurred after 693 bypass operations (574 anatomic and 119 extra-anatomic) performed in 10 consecutive years (1997-2006). The bypass graft failures (infection + thrombosis) treatment and the subsequent evolution of the patients were detected by analyzing patients’ readmissions made to solve these major post-bypass complications. The follow-up period extended up to 12 years after the primary arterial bypass reconstruction. In this period we registered: 89 secondary arterial reconstructions for early and late graft thrombosis; 8 healings after removal of the infected prostheses, followed by extraanatomic bypass operations (7 obturator bypass + 1 axillo-bifemoral bypass). The most frequent vascular prosthesis infection sites were the Scarpa triangle and the thoraco-abdominal subcutaneous segment of the axillo(bi)-femoral graft. Major amputations after extraanatomic bypass operations: at 4 years postoperatively for axillo(bi)-femoral operations the amputation rate was 17.6%, while for crossover operations it was 7.5%. Perioperatory mortality after anatomic bypass operations = 2 intraoperatory and 8 postoperatory (1.38%/574 operations); perioperatory mortality after extraanatomic bypass operations: 2 postoperatory deaths (1.68%/119 operations), 1 after axillo-femoral prosthesis infection and 1 after acute myocardial infarction. In order to reduce the graft major complication rate after extraanatomic bypass operations we took the following measures: 1. When there are arterial occlusive lesions distal to the femoral tripod we ensured an adequate outflow which favores the long-term patency of the extraanatomic graft; this goal was obtained by 2 methods: by enlargement profundoplasty and/or by performing an additional distal bypass towards the popliteal artery or towards the subgenicular arteries. The distal subgenicular anastomosis was made between a venous graft and the distal outflow artery for reducing the intimal hyperplasia. 2. For crossover bypass operations we often used autologous vein grafts; 3. In crossover ilio-femoral bypass operation with venous graft we avoid the graft compression in its path through abdominal wall by passing the graft through a stable caliber hole made in a polypropylene closure mesh of the abdominal wall. 4. We promote the tunneling of the axillo-femoral prosthesis through the subaponeurotic muscular tissue because this tissue better protects the prosthetic graft against infection. 5. In order to reduce the groin prosthesis infections, we prefer performing ilio-femoral crossover bypass instead of femoro-femoral one. 6. The obturator bypass remains a valuable tratment for groin infected prosthesis.
Lawrence Baruch
Kirtipal Bhatia, MD& Persio David Lopez, MD
Olga Sherman, PharmD
Abstract
Direct oral anticoagulants are recommended as first line therapy for patients with atrial fibrillation and venous thromboembolic disease. Measurement of drug levels or pharmacodynamic effect is not recommended during treatment. Dose adjustments are based on age, weight, kidney function and drug-drug interactions. These adjustments are generally based on an estimate of their effect on drug concentration. DOAC dosing recommendations differ across the world. These differences in prescribing recommendations result in different levels of DOAC exposure in patients with identical clinical characteristics. Additionally, data from clinical trials has shown that drug levels may vary significantly in individual patients with identical clinical characteristics despite taking the same prescribed dose. More concerning is that current prescribing recommendations provide cut points for dose adjustments, as an example age 80 or greater in the case of apixaban in atrial fibrillation, which may result in dramatically higher drug concentrations in patients with significantly higher bleeding risk.
Data from outcome trials in both atrial fibrillation and venous thromboembolism have provided mean-median drug concentrations for each of the DOACs. These trial results appear to demonstrate that once a threshold DOAC plasma concentration is reached, higher concentrations fail to provide significant added ischemic stroke reduction while at the same time add an increased risk of bleeding. Bleeding remains a significant problem with DOACs and is associated with an increase in short and long-term mortality, ischemic stroke, myocardial infarction, cost, and drug interruption and discontinuation.
Over the past years, our clinic has been assessing DOAC concentration in patients at risk for under or over exposure. Based on our experience, clinical characteristics alone appear to be insufficient, as a significant number of patients with characteristics suggesting high exposure would be under-dosed using a purely clinical approach and an even greater number, who are at elevated risk of bleeding would have had excessive levels, if prescribing were based strictly on the established dose reduction criteria. We propose, and provide our supporting clinical experience, that measuring DOAC levels in select patients will increase the margin of safety of these medications without compromising efficacy.
Abstract
There have been significant improvement in the care of acute ischemic stroke (AIS) resulting in reducing death and improving outcomes. Numerous groundbreaking positive randomized controlled trials have demonstrated that strokes with large vessel occlusion (LVO) treated with endovascular mechanical thrombectomy (EVMT) with standard treatment are associated with much better outcomes compared to those treated only with standard therapy. Additional evidence also revealed that the positive outcomes continue to persists for stroke patients with large vessels occlusion if they are treated with 24 hours of symptoms including those with wake-up stroke. The evidence suggests that for every two-patient treated with EVMT, one patient can be saved, which is the highest evidence in the medicine surpassing acute myocardial infarction and other acute lifesaving therapies. Based on these evidence, the local, National and International organizations have updated the guidelines in the treatment of AIS which have remarkably strengthen the process, pathways and standards for acute ischemic stroke management in the developed countries. However, not much progresses have made in the developing and third-world countries for stroke therapies, because of cost, affordability and there are no third-party payers. Most recent trials have further discovered that stroke patient with LVO and a large core volume treated with endovascular perfusion therapy in conjunction with standard treatment do significantly better comparted to standard treatment alone. New trials have also demonstrated that stroke patients undergoing EVMT with or without thrombolytic have equal functional outcome. Additional evidence suggests that non-disabling stroke patients treated with dual antiplatelet have equal functional outcome with less bleeding risk compared to intravenous thrombolysis. These evolving evidences have provided us with the opportunities to simplify the algorithm and treatment of acute ischemic stroke, which not only will cutdown time by eliminating unnecessary steps and redundant therapies, but also will reduce the healthcare cost and improving global access, specially, countries where patients bear the costs. In this review, author presents real life stroke patients treated based on recent evidence and provides with a simple and swift algorithm, that will reduce time to perfusion therapy and will make treatment affordable globally.
Abhinav Shrivastava
Department of Cardiology, Maharaja Agrasen Hospital, New Delhi, India.
Preetika Maurya
Department of cardiology, Base Hospital Delhi Cantt, New Delhi, India.
Sunny Pathania
Army Institute of Cardiothoracic Sciences (AICTS), Pune, Maharashtra, India.
Sugam K Singh
Army Institute of Cardiothoracic Sciences (AICTS), Pune, Maharashtra, India.
Sanya Chhikara
Jacobi Medical Center, Bronx, New York, USA.
Ashwin Mahesh
Department of Cardiology UPMC Harrisburg Pennsylvania, USA.
Balwinder Singh
Army Institute of Cardiothoracic Sciences (AICTS), Pune, Maharashtra, India.
Navreet Singh
Army Institute of Cardiothoracic Sciences (AICTS), Pune, Maharashtra, India.
Ranjit Kumar Nath
Department of Cardiology, Dr RML Hospital & ABVIMS, New Delhi, India.
Nalin Kumar Mahesh
St. Gregorios Medical Mission Hospital, Parumala, Kerala, India.
Nitin Bajaj
Army Institute of Cardiothoracic Sciences (AICTS), Pune, Maharashtra, India.
Prafull Sharma
Department of Cardiology, Army Hospital Research and Referral, New Delhi, India.
Prashant Panda
Department of Cardiology, Advanced Cardiac Centre, PGIMER, Chandigarh, India.
Jaskaran S Dugal
Deapartment of Cardiology, Jehangir Hospital, Pune, India.
Ankush Gupta, MD, DM, FACC
Professor of Medicine and Interventional Cardiologist, Army Institute of Cardiothoracic Sciences (AICTS), Pune, India.
Abstract
Introduction: Contemporary evidence suggest the comparable performance of biodegradable polymer sirolimus eluting stents (BPSES) with that of second generation durable polymer drug eluting stents. This study was done to evaluate the performance of BPSES in all comer patients undergoing percutaneous intervention (PCI) in real world setting over a period of three years.
Materials & Methods: This was a prospective observational study, wherein all comer consecutive patients undergoing PCI with BPSES (Yukon Choice Elite stent by Translumina Therapeutics, India) were enrolled and followed up for 3 years. The study’s primary endpoint was the Device Oriented Composite Endpoint (DOCE), which included cardiac death, target vessel myocardial infarction (MI), and clinically driven target lesion revascularization (TLR); the co-primary endpoint was the Patient-Oriented Composite Endpoint (POCE), which included all-cause mortality, any MI , and any repeat revascularization and the secondary endpoint was definite or probable stent thrombosis (DST & PST).
Results: 301 patients with 502 lesions were treated with 485 BP-SES. Mean age of the study cohort was 61.6± 9.3 yrs and males were 79.1%. 18.6% patients were diabetic, 29.6% had ejection fraction less than 40% and 73.1% patients presented with acute coronary syndrome (ACS). Majority of the patient had triple vessel disease (TVD) (51.8%), multivessel PCI was done in 15.6% and complex PCI in 26.2% patients. A mean of 1.6 ±0.8 stents per patient with mean diameter 3.0 ± 0.3 mm and mean length of 27.2 ± 0.8 mm were placed. DOCE & POCE occurred in 7.9% (cardiac death-4.8%, TLR-2.6% & target vessel MI-0.4%) and 12.8% (All deaths-9.7%, any MI- 0.4% and any revascularisation-2.6%) patients respectively at three years follow-up. DST & PST rate was 0.9% and 0.4% respectively in the study cohort. All the cases of stent thrombosis occurred within 30 days. Kaplan Meier analysis revealed that diabetes mellitus, low ejection fraction (EF), acute coronary syndrome (ACS), long stents and complex intervention had no impact on occurrence of DOCE & POCE while using BP-SES in all-comer patient population.
Conclusion: Present study showed favourable long term safety and efficacy profile of BP-SES for all-comer patients undergoing PCI.
Aynur Ozge, MD, PhD
Department of Neurology, Mersin University School of Medicine, Mersin, Türkiye
Reza Ghouri
Department of Neurology, Brain 360 Integrative Center, İstanbul, Türkiye
Derya Uludüz
Department of Neurology, Brain 360 Integrative Center, İstanbul, Türkiye; Department of Neurology, Cerrahpaşa University Medical Faculty, İstanbul, Türkiye
Abstract
This comprehensive review examines the impact of vascular risk factors on the phenotypic expression of migraine in the elderly population. Migraine, particularly migraine with aura, has been established as a risk factor for ischemic lesions of the brain, stroke, and other cardiovascular diseases. The association between migraine and specific vascular events, such as stroke, myocardial infarction, and angina pectoris, underscores the need for a comprehensive understanding of the interplay between migraine and cardiovascular diseases. The challenges in differentiating migraine from vascular insults, especially in the elderly population, highlight the need for improved diagnostic and treatment strategies to address the complexities of managing migraine in this demographic. Patient education and treatment of modifiable risk factors may decrease future vascular events, emphasizing the importance of addressing vascular risk factors in migraine management. The potential impact of prevention and treatment of unfavorable arterial hemodynamics on neurocognitive outcomes underscores the broader implications of addressing vascular risk factors in migraine management. The clinical and public health relevance of understanding the modifiability of vascular risk factors in elderly migraine patients extends to addressing challenges in cancer survivorship, radiological emergency response, and rational person behavior, emphasizing the diverse applications of addressing vascular risk factors in healthcare and public health. Ultimately, the clinical and public health relevance of understanding the impact of vascular risk factors on the phenotypic expression of elderly migraine underscores the need for continued research and clinical vigilance in addressing the complex interplay between migraine and vascular risk factors in the elderly population.
Pancreaticoduodenectomies in a Low Volume, Small Island Eastern Caribbean State: A Retrospective Cohort Study
Abstract
Background: Although pancreaticoduodenectomy (PD) is safe when performed in high-volume hospitals, many patients in low-income countries cannot access these hospitals. Barbados is a small island that does not have a high-volume pancreatic center. We sought to document peri-operative outcomes when PD was performed in Barbados.
Methods: We carried out a retrospective cohort study of all consecutive patients who underwent PDs over from August 1, 2016 to October 30, 2022. Therapeutic outcomes, post-operative morbidity and mortality were evaluated. Statistical analyses were performed using SPSS ver 16.0.
Results: Six patients at a mean age of 54.8 years underwent PD (mean annual case volume of 1). Two patients underwent planned vein resections and reconstruction. In this subset, the mean operating time was 325 minutes (Range 300-250; Median 325; SD ±35.4), mean estimated blood loss was 825mls (Range 750-900; Median 825; SD±106.1), and the mean transfusion requirement was 1 unit of packed cells (Range 0-2; Median 1; SD±1.41).
In the four patients without vein resection, mean operating time was 308 minutes (Range 280-350; Median 300; SD±24.01), median blood loss was 575 ml (Range 150-900; Median 700; SD±320.6) and mean transfusion requirements were 0.5 units of packed cells (Range 0-2; Median 0; SD ±0.84).
The mean ICU stay was 2.17 days (Range 1-3; Median 2.5; SD±0.98), and the mean duration of hospitalization was 9.3 days (Range 7-11; Median 9.5; SD±1.37). There were no recorded peri-operative deaths, but there was 1 (17%) minor complication (delayed gastric emptying) and 1 (17%) major complication (myocardial infarction).
Conclusion: In Barbados, there are good peri-operative outcomes after PD despite the low volume and challenging healthcare environment. We believe that (1) surgeon experience (2) continuous adaptive hospital learning and (3) regular audit of hospital data are better indicators of PD quality than volume data alone.
Jacques Fair
Bachelors of Science, USA
Esperanza Acuna
Bachelors of Science in Physiology, USA
Robert Roberts
Executive Director of the Heart and Vascular Institute, St. Joseph’s Hospital and Medical Center in Phoenix, USA
Abstract
Coronary artery disease (CAD) is the number cause of death in the world. It is estimated that 50% of Americans will experience a cardiac event in their lifetime. The underlying pathology leading to coronary artery disease and its clinical manifestations, such as angina, myocardial infarction, and sudden death is coronary atherosclerosis. While the disease is not usually manifested clinically until the sixth or seventh decade, the underlying pathology is initiated as early as the second or third decade. Numerous randomized clinical trials have shown cardiac morbidity and mortality can be prevented by lowering the risk of known conventional risk factors for CAD such as decreasing plasma cholesterol or controlling hypertension. Secondary prevention of these conventional risk factors has been very effective; however, primary prevention has been shown to be even more effective. A major barrier to primary prevention is the lack of markers to detect among young asymptomatic individuals those at risk for CAD. The conventional risk factors are often not present until the sixth or seventh decade which could be late for primary prevention. Genetic predisposition accounts for 50% of the risk for CAD. Recently over 200 genetic risk variants predisposing to CAD have been discovered. Based on these variants, one can express the genetic risk for CAD in a single number referred to as the Polygenic Risk Score (PRS). The PRS has been evaluated in over one million individuals and shown that those with high genetic risk have the highest incidence of heart disease and can be reduced by 40-50%, utilizing drugs (statins and PCSK9 inhibitors) or lifestyle changes (favorable diet and increased exercise). The genetic risk for CAD is determined at conception and thus can be predicted anytime from birth onward. The PRS detection of young asymptomatic individuals based on the PRS enables one to implement early primary prevention. Adoption of the PRS to risk stratify for CAD could represent a paradigm shift in the prevention of this pandemic disease.
Challenges and Opportunities in Leukemia
Challenges and Opportunities in Leukemia
Christopher K. Williams, MD FRCPC
Abstract
The African environment has for millennia been dominated by rampant agents of infections, of which malaria is among the best known, virtually uncontrolled, and associated with lifelong human struggles, ameliorarated by measures as socioeconomicaly affordable. This has led to the emergence of a variety of genetic aberrations, some of which are deleterious, resulting in major disease dysparities, including benign ones like sickle cell disease, and malignancies like the leukaemias, lymphomas, and breast cancer. They include the reduced incidence and the absence of its peak in acute lymphoblastic leukaemia in the first quinquennium of Nigerian children, which is otherwise typically seen in the children of high-income countries. Conversely is the observation in acute myelogenous leukaemia, with its chloroma-associated variant and its incidence peaking in the second quinquennium. This epidemiology is akin to the recent observation of acute myelogenous leukemia among sickle cell disease patients among the people of African descent in California, USA. Chloroma-associated acute myelogenous leukemia, and Burkitt lymphoma are linked with low socioeconomic status, an epidemiological feature that is shared with triple negative breast cancer patients in West Africa and the women of African descent in the United States. While a role for the malaria-associated genetic aberration underlying the Duffy null genotype is confirmed in the diversity of the triple negative breast cancer in the women of West Africa and those of African descent in the United States, it is conceivable, but not yet established in acute myelogenous leukemia. The zoonosis-linked human T-cell lymphotropic virus type 1 infection is associated with at least 17% of non-BL-non-Hodgkin lymphoma in form of its sentinel disease, the adult T-lymphoma/leukemia, but unexpicably much lower than the 50-60% of other major endemic zones of Japan and the African descendants of the Caribeean. This report describes the clinical, laboratory, and epidemiological features of leukemia and lymphoma cases diagnosed between 1982 and 1984 in the city of Ibadan, Nigeria, some of the features of which are reminiscent of the observations of Ludwig Gross’s experiments on environmental influences, such as malnutrition and infections, on animal leukemogenesis. These events are the consequences of the primordial pressures that have shaped human genetics and pathophysiology. Evidence provided in this study, indicating association of increasing socioeconomic status with increasing frequency of the c-ALL subtype, is indicative of the prospects for leukemogenesis of acute lymphoblastic leukemia and its epidemiology in Nigerians. Some findings reported here indicate the influence of the African genetic ancestry in the etiology of acute myelogenous leukemia, while socioecomic status is linked to the etiology of childhood acute lymphoblastic leukemia, as well as a variant of chronic lymphocytic leukemia, and the chloroma-associated acute myelogenous leukemia. These observations are suggestive of the existence of pathways to etiological discoveries in the leukemias. Observations reviewed in this paper reflect examples of changes that have occurred over the past 200 years in the societal perception of health challenges among the new-found communities of colonial Africa and the Americas – from the reductionistic connotations such as in the “virgin-soil theory” – towards that of social determinants of health.
María Alejandra Deu
Pediatric Hematology Oncology Department, Hospital de Pediatría “Prof. Dr. Juan P. Garrahan”, Buenos Aires C1245, Argentina.
María Ceciclia Bertone
Pediatric Hematology Oncology Department, Hospital de Pediatría “Prof. Dr. Juan P. Garrahan”, Buenos Aires C1245, Argentina.
Luisina Belén Peruzzo
Pediatric Hematology Oncology Department, Hospital de Pediatría “Prof. Dr. Juan P. Garrahan”, Buenos Aires C1245, Argentina.
Carla Luciana Pennella
Pediatric Hematology Oncology Department, Hospital de Pediatría “Prof. Dr. Juan P. Garrahan”, Buenos Aires C1245, Argentina.
Cristian Germán Sanchez La Rosa
Pediatric Hematology Oncology Department, Hospital de Pediatría “Prof. Dr. Juan P. Garrahan”, Buenos Aires C1245, Argentina.
Myriam Ruth Guitter
Pediatric Hematology Oncology Department, Hospital de Pediatría “Prof. Dr. Juan P. Garrahan”, Buenos Aires C1245, Argentina.
Elizabeth Melania Alfaro
Pediatric Hematology Oncology Department, Hospital de Pediatría “Prof. Dr. Juan P. Garrahan”, Buenos Aires C1245, Argentina.
Pedro Zubizarreta
Pediatric Hematology Oncology Department, Hospital de Pediatría “Prof. Dr. Juan P. Garrahan”, Buenos Aires C1245, Argentina.
María Sara Felice
Pediatric Hematology Oncology Department, Hospital de Pediatría “Prof. Dr. Juan P. Garrahan”, Buenos Aires C1245, Argentina.
Abstract
Spinal cord compression (SCC) is an unusual manifestation of leukemias and lymphomas in children and defines an oncological emergency frequently unsuspected, being a cause of severe sequelae. Our aim was to analyze the characteristics of patients who presented signs or symptoms of spinal cord compression in early phases of malignant hematopoietic diseases. From November-1988 to July-2022, 3878 patients with leukemia and lymphoma were diagnosed. Of them, 36 children (0.92%) presented spinal cord compression signs/symptoms in early phases of their diagnosis: Acute Lymphoblastic Leukemia (n=18), Acute Myeloblastic Leukemia and Myeloid Sarcoma (n=7), Non-Hodgkin Lymphomas (n=9) and Hodgkin Lymphoma (n=2). Clinical characteristics, images and hematological findings, treatment strategies, results and sequelae were analyzed. Sex distribution was 3.5/1 (M/F) and the media age at diagnosis was 10 (range: 4.9-16.9) years. The most common symptoms were back pain (34/36), functional impotence (27/36) and sphincter compromise (10/36). The media time from symptom onset to diagnosis was 47,5 (range: 0-300) days. Magnetic resonance imaging was performed on 33 (92%) patients and showed epidural mass (n=16) or vertebral collapse (n=17) in all of them. Two patients received initial radiotherapy and 11 decompressive surgeries for the management of the urgency spinal cord compression. Bone marrow aspiration was the diagnostic procedure in 69% of cases. All patients received chemotherapy and 94% achieved complete remission. Severe sequelae were observed in 10 patients (paraplegia with neurogenic bladder and kyphoscoliosis). Leukemia and lymphoma should be considered as a differential diagnosis when spinal cord compression is suspected, and magnetic resonance imaging is the mandatory study to confirm this diagnosis as a matter of urgency. Bone marrow involvement was evident due to hematological alterations in 95% of cases allowing to guide the diagnosis and initiate treatment early to reduce sequelae.
Natalia Neparidze, MD
Yale University School of Medicine New Haven, CT
Krystal W. Lau, PhD
Flatiron Health, New York, NY
Xiaoliang Wang, PhD
Flatiron Health, New York, NY
Scott Huntington, MD, MPH
Yale University School of Medicine New Haven, CT
Omer Jamy, MD
University of Alabama at Birmingham, Birmingham, AL
Gregory S. Calip, PharmD, MPH, PhD
Flatiron Health, New York, NY
Harsh Shah, DO
University of Utah, Huntsman Cancer Center, Salt Lake City, UT
Deborah M. Stephens, DO
University of Utah, Huntsman Cancer Center, Salt Lake City, UT
Rebecca Miksad, MD, MPH
Flatiron Health, New York, NY
Ravi B. Parikh, MD, MPP
University of Pennsylvania, Philadelphia, PA
Samuel Takvorian, MD, MSHP
University of Pennsylvania, Philadelphia, PA
Gaurav Goyal, MD
University of Alabama at Birmingham, Birmingham, AL
Erlene Seymour, MD
Flatiron Health, New York, NY
Abstract
Background: The COVID-19 pandemic impacted healthcare visit trends, transitioning care to utilize telemedicine. We aimed to investigate if the uptake in telemedicine during pandemic was equitable across racial groups for patients with hematologic malignancies.
Methods: Using the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database we analyzed patients with diagnosis of acute myelogenous leukemia (AML), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL) or multiple myeloma (MM). Patients were categorized into treatment types within lines of therapy: outpatient (oral therapy and outpatient infusions combined with oral therapy) vs. inpatient treatments (chemotherapy, cellular therapy). Monthly visit rates were calculated as the number of visits (telemedicine or in-person [in-clinic treatment administration, vitals, and/or labs]) per active patient per 30-day standardized month. We used time-series forecasting methods on pre-pandemic monthly visit rate data (March 2016 – February 2020) to estimate projected counterfactual monthly visit rates between March 2020 – February 2021.Telemedicine uptake was descriptively analyzed over time (t).
Results: We included 18,924 active patients (2,394 Black and 16,530 White) and 884,504 visits (117,673 Black and 766,831 White). 4,053 AML, 3,468 diffuse large B cell lymphoma, 1,943 follicular lymphoma, 2,151 mantle cell lymphoma, 5,926 chronic lymphocytic leukemia and 7,752 myeloma patients. Black patients had no significant reductions in in-person visit rates throughout the pandemic period compared to the projected rates. Conversely, White patients experienced an 18% (95% PI 9.9% – 25%) lower rate of in-person visits for outpatient therapy during the early pandemic (March – May 2020) (actual monthly visit rate 1.61; projected visit rate 2.0 [95% CI 1.8-2.2]). Telemedicine uptake was significantly higher for White patients compared with Black patients for all diseases and treatment categories between March 2020-February 2021 (t = 9.5, p < 0.01), AML inpatient (t = 2.4, p = 0.04), MM outpatient (Figure 3C) (t = 6.0, p < 0.01) and MM inpatient treatment categories (Figure 3D) (t = 2.3, p = 0.04).
Conclusions: White patients had significantly higher telemedicine uptake compared with Black patients for all treatment categories. These findings challenge healthcare systems to direct efforts toward reducing the gap in healthcare access.
Dhanya Mohan
Amna Khalifa Alhadari
Dileep Kumar
Sima Abdolla Nejad
Rahaf Mohamad Wardeh
Department of Internal Medicine, Dubai hospital, Dubai, United Arab Emirates
Batool Khan
Dubai Medical College for Girls, Dubai, United Arab Emirates
Madheeha Mahmood
Dubai Medical College for Girls, Dubai, United Arab Emirates
Zuha Fathima
Dubai Medical College for Girls, Dubai, United Arab Emirates
Mohammed Railey
Department of Neprology, Dubai hospital, Dubai, United Arab Emirates
Abstract
Cryoglobulinemic vasculitis presents with systemic vasculitis including vasculitic rash, fever, peripheral neuropathy, and, in rare cases renal involvement. This could be secondary to infections like hepatitis C, malignancies like myeloma, Non Hodgkin’s lymphoma and chronic lymphocytic leukemia. We encountered a patient who presented with fever, anemia, purpuric skin rash and acute kidney injury due to acute glomerulonephritis with nephritic picture and fluid overload that required hemodialysis.Investigations revealed hemolytic anemia, cryoglobulinemia, proliferative glomerulonephritis with Ig M intra-capillary deposits and hyaline thrombi. Bone marrow biopsy clinched the diagnosis of Chronic lymphocytic B cell lymphoma with CD 20 positivity. Treatment was instituted with Rituximab and Bendamustine. Plasmapheresis was done for hyperviscosity syndrome. With treatment, hemodialysis could be discontinued after 10 weeks and renal functions recovered partially with serum creatinine settling at 1.5 mg/dl. We present this case to highlight the presentation of chronic lymphocytic leukemia with cryoglobulinemic vasculitis that presented with purpura and rapidly progressive renal failure that required dialysis.
Richard L. Momparler
Département de pharmacologie-physiologie, Université de Montréal; Centre de recherche, Service d’hématologie-oncologie, CHU Sainte-Justine, Montreal, Quebec H3T 1C5, Canada
Sylvie Côté
Centre de recherche, Service d’hématologie-oncologie, CHU Sainte-Justine, Montreal, Quebec H3T 1C5, Canada
Louise F. Momparler
Centre de recherche, Service d’hématologie-oncologie, CHU Sainte-Justine, Montreal, Quebec H3T 1C5, Canada
Abstract
Complete eradication of leukemic stem cells (LSCs) in patients with acute myeloid leukemia (AML) is required for curative therapy. Epigenetic alterations that involve gene-silencing by DNA methylation by DNMT1, methylation of H3K27 by EZH2 histone methyltransferase (HMT) and methylation of H3K9 by G9a HMT may play a major role in the development of AML. The major action of these epigenetic alterations is the silencing of the genes that program differentiation of AML cells. Inhibitors of DNA and histone methylation have the potential to reverse this block in differentiation. If tumor suppressor genes (TSGs) contain two gene-silencing markers, such as DNA methylation and H3K27me3, they may not be fully reactivated with only an inhibitor of DNA methylation, such as 5-aza-2’-deoxycytidine (5-AZA-CdR), but may also require an inhibitor of EZH2. In support of this model is the synergistic antileukemic action as shown by a colony assay on AML cells using 5-AZA-CdR in combination with 3-deazaneplanocin A (DZNep), a potent inhibitor of EZH2. A similar type of interaction can occur when TSGs are silenced by DNA methylation and the G9a methylation of H3K9me2, a second gene-silencing marker. Treatment of these AML cells with 5-AZA-CdR and BIX01294, an inhibitor of G9a, also results in a synergistic antileukemic action. Leukemic cells that contain 3 different gene-silencing markers: DNA methylation, H3K27me3 and H3K9me2 may require 3 different inhibitors for maximal antineoplastic activity. This result was observed when the AML cells were treated in with 5-AZA-CdR, DZNep and BIX01294. The aim of this study was to demonstrate that epigenetic agents that target DNA and histone methylation have remarkable antineoplastic activity against myeloid leukemia cells. The second aim was to propose a dose-schedule for these epigenetic agents that can be evaluated in a clinical trial in patients with advanced AML for its potential to eradicate LSCs. One of the most sensitive targets for chemotherapeutic intervention in LSCs is the block in differentiation due to gene-silencing by DNA and histone methylation. Epigenetic agents that have the potential to reverse this block merit clinical investigation with high priority.
Abstract
Background: Several studies of the health problems incurred by flight attendants flying during the smoking years concluded that they suffered elevated rates of chronic bronchitis, heart disease, skin cancer, breast cancer, melanoma, reproductive cancers, middle ear infections, hearing loss, asthma, pneumonia, chronic obstructive pulmonary disease, various pulmonary function abnormalities, plus depression and anxiety.
Aims: Systematic review of secondhand smoke risks to flight attendants, exemplified using a specific case involving a deceased flight attendant who suffered from a multiplicity of tobacco-smoke-related diseases, including asthma, breast cancer, carotid artery stenosis, cataracts, cervical cancer, chronic obstructive pulmonary disease, coronary artery disease, laryngeal cancer, pneumonia and chronic myeloid leukemia. The decedent died in 2014 at age 68, losing an estimated 18.5 years of life expectancy.
Methods: Pharmacokinetic modeling was used for the first time to estimate the risk from secondhand smoke for flight attendants on typical passenger aircraft flown by the decedent during an 18 year period ending in 1988.
Results: Based on in-flight cotinine dosimetry measured in an Air Canada study, typical flight attendants would have inhaled a dose-equivalent of fine particle air pollution exceeding the “Air Pollution Emergency” levels of the U.S. Environmental Protection Agency’s Air Quality Index. The secondhand smoke cotinine dose for typical flight attendants in aircraft cabins is estimated to have been 6-fold that of the average US worker and 14-fold that of the average person. Thus, ventilation systems massively failed to control secondhand smoke air pollution in aircraft cabins, and led to extreme exposures. The decedent’s estimated lifetime cancer risk from secondhand smoke was 18 times U.S. OSHA’s Significant Risk of Material Impairment of Health level of 1 per 1000 per working lifetime.
Conclusions: In-flight exposure to toxic and carcinogenic tobacco smoke in smoky passenger cabins was the major risk factor leading to the decedent’s multiple smoking-related diseases, and her premature death. This has implications for the extant and future health of the cohort of surviving flight attendants exposed to secondhand smoke on aircraft during the 20th Century Era.
Evelim Leal de Freitas Dantas Gomes, Dr
São Paulo University USP
Carolina Cristina Santos Camargo
Ibirapuera University
Debora Nunes Prata Anjos
Ibirapuera University
Etiene Farah Teixeira de Carvalho
FacPhysio
Abstract
Onco-hematological diseases are serious conditions and often require aggressive treatment that can lead to systemic complications, consequently affecting musculoskeletal functions as well as physical and functional capacity. Respiratory complications can lead to a greater frequency of hospitalizations and immobility, creating a cycle of sedentarism as well as an increase in morbidity and mortality. The goal of physical therapy in such cases is to restore compromised functions in affected children and adolescents and ensure the performance of activities of daily living and better development.The aim of this review was to bring to light the dysfunctions promoted by onco-hematological diseases of childhood in order to understand the best way to approach the treatment for this population.In this review, the functional alterations of sickle cell anemia, leukemia and bone marrow transplantation were addressed, as well as the interventions used by physiotherapy for the treatment.
Ying Xiong
Caring Cross, 910 Clopper Rd., Suite 200 S, Gaithersburg, MD 20878 USA
Yanping Xie
Caring Cross, 910 Clopper Rd., Suite 200 S, Gaithersburg, MD 20878 USA
Zhongyu Zhu
Caring Cross, 910 Clopper Rd., Suite 200 S, Gaithersburg, MD 20878 USA
Ibeawuchi Oparaocha
Caring Cross, 910 Clopper Rd., Suite 200 S, Gaithersburg, MD 20878 USA
Oxana Sleesareva
Caring Cross, 910 Clopper Rd., Suite 200 S, Gaithersburg, MD 20878 USA
Boro Dropulić
Caring Cross, 910 Clopper Rd., Suite 200 S, Gaithersburg, MD 20878 USA
Rimas J. Orentas
Caring Cross, 910 Clopper Rd., Suite 200 S, Gaithersburg, MD 20878 USA
Abstract
The creation of autologous gene-modified cell products, such as CAR-T cells (chimeric antigen receptor T cells) has met with clinical success but has been severely restricted by cost, availability, and current commercial models of central manufacturing. Moreover, the inability to produce CAR-T cells at reasonable cost in all but the largest centers slow innovation. CAR-T cells are unique in that these ex vivo expanded effector T cell populations express activation receptors comprised of immunoglobulin-like binders, or other immune ligands, bypassing the restriction of expanding and appropriately activating effector cells that arise by recombination of V-D-J genetic elements. However, the use of a single binding moiety to recognize leukemia target cells has selected for the generation of escape mutants, or for cryptic clones to expand that were not initially detected upon diagnostic work-up. To meet this challenge, we have engineered both B cell malignancy-specific and HIV surface antigen-specific CAR-T cells that express multiple binding moieties, thereby reducing the chance of immune escape. The creation of a therapeutic CAR-T cell population also requires a complex set of procedures that includes procurement of a large number of patient T cells, most often by leukapheresis, activation of the T cell population using matrix-associated antibodies targeting the T cell receptor and an immune co-receptor, a gene vector to permanently transduce T cells, and a bioreactor that can accommodate the expansion of the engineered cell population to numbers suitable for infusion. This complex set of procedures, combined with the current central processing model, has led to a complex chain of custody and expensive temperature-controlled shipping requirements. We present here a model whereby production of CAR-T cells at the point of care, using simplified cell procurement, purification, and expansion, can reduce the time and expense of CAR-T cell generation, with the aim to expand the use of these therapies in both the majority world, and in managed care or publicly funded systems. The CAR-T populations produced in this point-of-care ready process are highly active, viable, and have preferred CAR-T phenotypic characteristics associated with clinical efficacy.
Maurizio Martellini
Scientific Director of Theranosti Centre Srl
Ka-Ngo Leung
Berkion Technology LLC
Giuseppe Gherardi
Theranosti Centre Srl
Lidia Falzone
Theranosti Centre Srl
Abstract
Alpha-particle emitting radioisotope Actinium225 (225Ac) is of great interest for use in Targeted Alpha Therapy (TAT) treatments of e.g., brain tumors, bladder cancer, neuroendocrine tumors and leukemia. A suitable 225 Ac radioligand is also potentially resolutive for the treatment of advanced and metastatic Castration-Resistant Prostate Cancers (mCRPCs). The mCRPC has a mean survival rate of 9-36 months and encompasses a heterogeneous ample range of molecular cancer behavior with a high risk of progression.
Global demand for the 225 Ac has spurred several production efforts including extraction from 233U, high energy protons or photon irradiation of 226Ra or spallation of 232Th by, at least, 100 MeV protons. Instead of using accelerators systems such as cyclotrons or LINACs, a Compact Neutron Generator (CNG) system has been developed. A 400kV-10 mA DC (D_7Li) CNG potentially able to produce substantial amount of 225Ac with low 227Ac impurities is here presented. Exploiting the high flux of 10 and 13 MeV energy neutrons generated by the (D_7Li) reactions to bombard a thin target layer of 226Ra, 225Ra/225Ac is produced via the 226Ra(n,2n)225Ra nuclear reaction. By irradiating a 5 mm thick 226Ra layer for 100 hours, about 11-13 mCi of 225Ac can be produced – corresponding to the TAT treatment of about 65 oncological patients – with an estimated 227Ac contamination of about one percent, which is below the acceptable limit for clinical use. This 225Ac production scheme by a suitable CNG should allow to adopt a local/regional approach avoiding the shipment costs of 225Ac.
The aim of this paper is to inform the production chain of radioisotopes to be used in medical field and the medical community involved in the application of radiopharmaceuticals for the cure of cancer, that a new technology based on Compact Neutron Generators (CNG) is in a R&D phase and will allow to produce the necessary quantity of radioisotopes for clinical and research purpose. This will be essential in treatment advanced metastatic cancer as for instance the metastatic Castration – Resistant Prostate Cancer.
Abstract
Successful cancer evolution (CE) relies on the sequential molecular and functional events including 1) telomere; 2) sub-telomere; 3) epigenetic; 4-6) hit-episodes; 7) an innovative cell cycle machinery, as the multi-phase, and 8) chromosomal abnormalities. In this regard, eight available, fundamental/evolutionary and strategic key information (Evolutionary- ID) presented.
Telomere length (TL), has the fundamental role in cancer development, with serious challenges in the clinical managements. Breast cancer and brain tumor are an unresolved problem in Science and Medicine. Besides, an early and translatable diagnostic- prognostic-predictive platform, by considering the targets-ID, is required. Diverse TL in two cases affected with astrocytoma with grade IV, revealed to be 12500 and 15000 bp in tumor, and 10000 and 9000 bp at genomic level. Interestingly, TL is declined in the lymph node, i.e., occurrence of evolution.
Sub-telomeres (STs) through the cellular journey, are the neighboring destination at genomic and somatic level. The evolutionary pattern of STs has not been, routinely, decoded to the personalized clinical managements. The ST–sequences, are diversely predisposed to variety of environmental factors and play influential role in healthy individuals and the patients. An early detection is available by analysis of the ST- hybridized signals in the biopsy of auxiliary lymph nodes (ALN), and/or by circulating tumor cells (CTCs) into the blood stream. Diverse pattern of signal frequency and intensity in individual chromosomes at both somatic (ALN) and genomic (lymphocytes) levels were remarkable. The most common involved targets included chromosomes 5 and 9, 16 and 19; with diverse intensity at p and q chromosomal arms respectively. These findings have the predisposing, and an initial influence through the patients’ course of disease.
ST- signals, by providing the STs-ID, offer periodical and predictive, indices in cancer screening and therapy.
Furthermore, the complementary, cell cycle protein expression (PE) including Ki67, cyclin D1, and cyclin E, accelerates an early clinical management through the period of disease based on the CTCs.
Epigenetics is the next molecular destination by focusing on the genomic/somatic index, as an evolutionary Epigenetics-ID with its impact on the cancer management. The target panel is Ataxia Telangiectasia mutated gene (ATM) as the molecular marker and an initiator of different cancers.
ATM has remarkable roles, including: 1) in DNA double strand break (DSB), 2) to initiate different types of neoplastic disorders, including cancer, and 3), polymorphism, D1853N as a peridisposing marker by initiating the hit process. The influential characteristics include: family history of neoplastic disorders through the pedigree, the key role of ATM promoter methylation, cooperation of ATM/Rb protein expression, D1853N- marker, telomere length (TL) and the clinico-pathological characteristics in different types of brain tumors, and the environmental factors. Interestingly, TL has an independent influence on the progressive cancer evolution. An early detection by CTCs based on the D1853N/Sub-TL/Cell cycle checkpoints based on the PE assay and molecular test facilitate an early detection and therapy, based on the personalized approach.
By highlighting the preventive insight in Medicine, a brief record on the “Methylation in Chorionic villus samples (CVS)” with aim of an early detective strategy is provided. All nine CVS samples were methylated for the MCPH1 gene. An early detection is possible either through CV sampling or by the circulating CV cells in the maternal blood.
Evolutionary Hit includes: presence of D1853N polymorphism of ATM, as the hit-initiator through an evolutionary and progressive molecular based sequential alterations led to discovery of three-hit hypothesis in a patient affected with astrocytoma. More hits include five, and eight- hit hypotheses in primary breast cancer patients. Such platforms are considered as the individualized model in cancer. The pedigrees and details at the molecular follow-up studies and functional alteration at protein level are available in the provided sections.
Novel strategy of Cell cycle phases in breast cancer is the major intersection for cancer therapy.
The novel cell cycle hypothesis (CCH) highlights the mosaic based of dual and/or multi-phases, as minor clones at single cell level in the breast cancer (BC) -patients, escorted by the normal cell population. Such mosaicism provided an archetypal, unique diagnostic and therapeutic model, by applying different mosaic patterns (MPs) as well as “G1/S, S/G2 and G1/S/G2, and accompanied by normal phases, as a sole including G1, S, and G2 at the single cells level.
Diagnosis is based on the mode of signal copy numbers (SCN) and the related PE. Interestingly MPs were also unmasked in patients with chronic myelogeneous leukemia and other solid tumors.
Finally, the predisposing/predictive/prognostic/preventive square provides an innovate CDKs inhibitor-based therapy in BC and other cancers.
Personalized base cancer therapy is the confusing procedure and requires the pedigree-based data, personalized, evolutionary based information including molecular and functional at both genomic and somatic, at single cell level. The target territories comprise cell cycle phases, proteins, Telomere length, telomerase, sub-telomere, and Epigenetics. The aim is directing the cell cycle fundamental forces back to normal, by performing:
1) Applying personalized, single cell-based approach, at molecular, functional level, pedigree analysis, and balancing the micro-/macro-environmental factors, including nutrition.
2) Satisfactory high single cell enumeration based on the FISH and protein expression assays;
3) Decoding the required dosage and combined therapeutic regimens accordingly,
4) Unmasking the cell cycle combined (mosaic) phases including different Cyclins; and
5) Bilateral cooperation between Pharmacology, Medicine, and Cancer Genetics/cell biology.
Let’s combine the evolutionary based strategy by translating the personalized data at molecular/ Functional/ Informative, and pedigree-based level to the personalized therapy.
Challenges and Opportunities in Immune Regulation
Challenges and Opportunities in Immune Regulation
Walker, M., Peppercorn, K., Kleffmann, T., Edgar, C. D., & Tate, W. P. (2023b)
Abstract
Viral infection in most people results in a transient immune/inflammatory response resulting in elimination of the virus and recovery where the immune system returns to that of the pre-infectious state. In susceptible people by contrast there is a transition from an acute immune response to a chronic state that can lead to an ongoing lifelong complex post-viral illness, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. This susceptibility is proposed to be genetic or be primed by prior health history. Complex abnormalities occur in immune cell functions, immune cell metabolism and energy production, and in cytokine immune modulator regulation. The immune system of the brain/central nervous system becomes activated leading to dysfunction in regulation of body physiology and the onset of many neurological symptoms.
A dysfunctional immune system is core to the development of the post-viral condition as shown with diverse strategies of immune profiling. Many studies have shown changes in numbers and activity of immune cells of different phenotypes and their metabolism. Immune regulating cytokines show complex altered patterns and vary with the stage of the disease, and there are elements of associated autoimmunity. These complex changes are accompanied by an altered molecular homeostasis with immune cell transcripts and proteins no longer produced in a tightly regulated manner, reflected in the instability of the epigenetic code that controls gene expression. Potential key elements of the altered immune function in this disease needing further exploration are changes to the gut-brain-immune axis as a result of changes in the microbiome of the gut, and viral reactivation from latent elements of the triggering virus or from a prior viral infection. Long COVID, an Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-like illness, is the post-viral condition that has arisen in large numbers solely from the pandemic virus Severe Acute Respiratory Syndrome Coronovirus-2. With over 760 million cases worldwide, an estimated ~100 million cases of Long COVID have occurred within a short period. This now provides an unprecedented opportunity to understand the progression of these post-viral diseases, and to progress from a research phase mainly documenting the immune changes to considering potential immunotherapies that might improve the overall symptom profile of affected patients, and provide them with a better quality of life.
Rosenthal, K. S., & Zimmerman, D. H. (2022)
Abstract
Autoimmune disease disrupts the normal immunological balance by promoting a perpetual cycle of innate/immune/inflammatory responses that continues due to the continued presence of antigen. The disease cycle is in turn amplified and regulated by cycles of antigen-specific T cell mediated immune responses. Removal of the stimuli or regulation of the disease drivers can stop the cycle to allow rebalancing and prevent the progression or chronicity of disease. As an alternative to the current treatments for autoimmune and inflammatory disease, which reduce, inhibit or eliminate the triggers, drivers or antigens, newer approaches stimulate regulatory responses, or inhibit or repurpose the effector/inflammatory responses to control the immune disease cycle. LEAPS (Ligand Epitope Antigen Presentation System) therapeutic vaccines for rheumatoid arthritis are presented as examples of therapies that elicit antigen specific T cell modulation of autoimmune and inflammatory responses to treat disease.
Walker, M., Hall, K. S., Peppercorn, K., & Tate, W. P. (2022)
Abstract
Long COVID is now well accepted as an ongoing post-viral syndrome resulting from infection of a single virus, the pandemic SARS-CoV-2. It mirrors the post-viral fatigue syndrome, Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome, a global debilitating illness arising mainly from sporadic geographically-specific viral outbreaks, and from community endemic infections, but also from other stressors. Core symptoms of both syndromes are post-exertional malaise (a worsening of symptoms following mental or physical activity), pervasive fatigue, cognitive dysfunction (brain fog), and sleep disturbance. Long COVID patients frequently also suffer from shortness of breath, relating to the lung involvement of the SARS-CoV-2 virus. There is no universally accepted pathophysiology, or recognized biomarkers yet for Long COVID or indeed for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Clinical case definitions with very similar characteristics for each have been defined. Chronic inflammation, immune dysfunction, and disrupted energy production in the peripheral system has been confirmed in Long COVID and has been well documented in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Neuroinflammation occurs in the brain in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome as shown from a small number of positron emission tomography and magnetic resonance spectroscopy studies, and has now been demonstrated for Long COVID. Oxidative stress, an increase in reactive oxygen and reactive nitrogen species, and free radicals, has long been suggested as a potential cause for many of the symptoms seen in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, resulting from both activation of the brain’s immune system and dysregulation of mitochondrial function throughout the body. The brain as a high producer of energy may be particularly susceptible to oxidative stress. It has been shown in peripheral immune cells that the balanced production of proteins involved in regulation of the reactive oxygen species in mitochondria is disturbed in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Fluctuations in the chronic low level neuroinflammation during the ongoing course of Long COVID as well as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome have been proposed to cause the characteristic severe relapses in patients. This review explores oxidative stress as a likely significant contributor to the pathophysiology of Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, and the mechanisms by which oxidative stress could cause the symptoms seen in both syndromes. Treatments that could mitigate oxidative stress and thereby lessen the debilitating symptoms to improve the life of patients are discussed.
Cardozo, D. M., De Barros-Mazon, S., Guimarães, F., Visentainer, J. E. L., & De Souza, C. A. (2024)
Abstract
The Natural Killer cells are innate lymphoid cells that play essential roles in defense against viral and parasitic infections, elimination of tumor cells, regulation of adaptive immunity through cytotoxicity, and cytokine secretion. Fundamental knowledge about the regulation of Natural Killer cells can be applied to study their function in patients undergoing hematopoietic stem cell transplantation, with or without Cytomegalovirus reactivation. The function of Natural Killer cells is governed by a repertoire of receptors responsible for initiating intracellular activating or inhibitory signaling. The balance of this signaling directs the cytotoxic activity of these cells, as well as cell proliferation and cytokine release.Understanding the interaction of receptors expressed on the surface of Natural Killer cells with their ligands expressed on target cells is a topic of discussion in the context of alloreactivity and the graft-versus-leukemia effect in transplant patients. Recent investigations have shown that KIR/HLA interactions go beyond affinity and describe that many of them depend on the peptide being presented by the HLA at that moment. Analysis of the peptidome (HLA class I + bound peptide) has demonstrated that some Natural Killer cell receptors are peptide-dependent. Therefore, understanding these interactions by considering the entire Natural Killer cell receptor + HLA class I + peptide complex is crucial in the reestablishment of immune cells after hematopoietic stem cell transplantation, especially in the context of Cytomegalovirus reactivation, which is very common in these patients. Hence, the aim of this study is to deepen our understanding of the specificity of interactions between human Natural Killer cell KIR receptors and the peptidome in the context of Cytomegalovirus reactivation after allogeneic, related, HLA-compatible hematopoietic stem cell transplantation without T-cell depletion. For the analysis of interactions between Natural Killer cell receptors and peptidomes, specific peptide libraries for HLA class I alleles will be created to evaluate the specificities of interactions between KIR + HLA class I + peptide.
Davis, P. J., Hercbergs, A., Lin, H., Leinung, M. C., & Mousa, S. A. (2023)
Abstract
Thyroid hormone as L-thyroxine (T4) at physiological concentrations acts at its cell surface receptor on integrin avb3 to stimulate cancer cell proliferation1. These proliferation studies have been conducted in vitro, but pharmacological reduction of T4 and substitution of nuclear receptor ligand 3,3’,5-triiodo-L-thyronine (T3) is a state of euthyroid hypothyroxinemia that has been shown clinically to arrest tumor growth in patients with cancer. T3 is inactive at physiological levels at the plasma membrane integrin receptor. A preclinical study of human basal cell carcinoma (BCC) cells has shown that the integrin thyroid hormone receptor regulates BCC radiosensitivity. While the large majority of BCCs are very manageable clinically, a small number of such tumors are aggressive. In this review of documented and proposed effects of T4 on BCC cells, we raise the possibility that BCC aggressiveness reflects T4 actions on its thyrointegrin target. The functions affected by T4 at the integrin in other human cancers include enhanced cell proliferation, anti-apoptosis, immune checkpoint regulation and metastasis, as well as state of radiosensitivity. The importance of investigating this possible pathophysiology is that euthyroid hypothyroxinemia may be tested as a treatment option.
Challenges and Opportunities in Emphysema
Challenges and Opportunities in Emphysema
Adekanye, A. G., Umana, A. N., Akintomide, A. O., Nakanda, B., Mgbe, R. B., Offiong, M. E., & Asuquo, B. 2017,
Abstract
Subcutaneous emphysema after adeno-tonsillectomy is rarely encountered. One of such cases following adenotonsilectomy was seen in our institution.
We report the case of a 5-year-old girl who developed cervicofacial emphysema and pneumomediastinum following retching and vomiting 6 hours after a routine adenotonsillectomy. Radiograph of the jaws and chest revealed subcutaneous emphysema. Previously published cases showed that the cause was most likely due to air passing into subcutaneous tissue through the tonsillar fossa and superior constrictor muscle into the facial layers of the neck following a bout of coughing and straining (crying), or the use of positive pressure ventilation. The emphysema can then spread to parapharyngeal and retropharyngeal spaces with associated morbidities. Further complications may include pneumothorax and pneumomediastinum and this should be excluded.Martínez‐Hernández, L., Jung, C. Y., Gerardo, M., Manuel, L., Claudia, L., & José, D. (2022)
Abstract
To date, few report cases of spontaneous pneumothorax, pneumomediastinum and subcutaneous emphysema without any cause of trauma have been observed in patients with COVID-19 pneumonia. We present a case of a 66-year-old male patient who developed such complication on day 19 of hospitalization, without requiring non-invasive or invasive ventilator. CT thorax scan revealed widespread bilateral ground glass opacities with pneumothorax, pneumomediastinum, and subcutaneous emphysema, which were resolved totally on the following 29 days. We highlight preexisting mechanisms for pulmonary air-leak syndrome and importance of prompt recognition to establish adequate therapy in patients with COVID-19 pneumonia.
Salinas, M., & Florenzano, M. (2021)
Abstract
Interstitial lung diseases (ILD) are a complex and diverse group of disorders. ILD are more frequently diagnosed and prevalent now. In this article, diagnosis approach, including new bronchoscopy and genetic tools, and some recently added concepts are revisited, as progressive fibrosing interstitial lung diseases and interstitial lung abnormalities.
Recently information relative to idiopathic pulmonary fibrosis is shown, including genetics and pathophysiology. We look over the dynamic world of interstitial lung diseases related to connective tissue diseases, principal characteristics of this group and the principles that define which of the various available therapies should be chosen. Finally new concepts and guidelines published about the diagnosis and management of hypersensitivity pneumonitis are reported. New data and treatments have changed our traditional vision of these lung diseases and we will new options in the next years.
Zhang, W., & Mehta, A. (2018, August 16)
Abstract
Background: Pursed lip breathing (PLB) is an important aspect of respiratory exercise training utilized by patients with chronic obstructive pulmonary disease (COPD) to alleviate symptoms of dyspnea. This modality became a part of the recommended treatment during pulmonary rehabilitation and was endorsed by ACCP/AACVPR (American College of Chest Physicians/ American Association of Cardiovascular and Pulmonary Rehabilitation) in 1997. 1 Theoretically, PLB promotes maximum exhalation by creating back-pressure inside the airways and thereby improving patency. These changes in respiratory mechanics counteract the pathophysiology leading to emphysema and optimize pulmonary function, thus decreasing dyspnea symptoms associated with dynamic hyperinflation. While there is no overwhelming evidence to support the efficacy of PLB, clinicians still encourage their patients to use PLB techniques during their pulmonary rehabilitation program.
Methods: A total of 26 research articles met criteria for inclusion in this review.
The purpose of this review is to better understand the historical perspectives and evidence surrounding the use of PLB.
Discussion: Most evidence suggested that PLB could be an effective self-care management that optimizes pulmonary function. The knowledge gained from this review may be used to explore implementation strategies utilizing pursed lip breathing exercises for developing a home-based pulmonary rehabilitation program in order to optimize pulmonary function and quality of life in COPD patients.
Palma, D., Cracchiolo, A., Librizzi, D., La Sala, A., & Agrusa, L. (2021)
Abstract
Introduction: The aim of our retrospective analysis is to evaluate the results of conservative management of acquired tracheoesophageal fistulae (TEF). TEF are rare but potentially life-threatening emergencies which can be of either spontaneous or iatrogenic origin. Spontaneous ones can be congenital or secondary to malignancy. For acquired ones numerous causes have been documented, the most common of which are endotracheal and tracheostomy tube-related injuries.
Methods: From February 2016 to March 2019 seven patients (5 men; 2 women) with acquired TEF were diagnosed in our intensive care unit (ICU). The injury occurred after dilational percutaneous tracheostomy in three patients, after esophageal endoscopy in one patient, after cuff-related ruptures in three intubated and mechanically ventilated patients. Our patients had no particular medical history. Mean age: 46 years. Mean duration of signs before diagnosis: 8 hours. The median length of the injury was 1,4 cm. The mean duration of hospitalization in the ICU was 31 days.
Results: All patients underwent conservative management: antibiotic therapy, close brochoscopic controls, percutaneous endoscopic gastrostomy and tomographic investigation. No mediastinitis was observed. Two patients died from causes unrelated to the tracheal injury.
Conclusions: Successful management of acquired TEF requires a fast and straightforward diagnostic evaluation. According to our experience, conservative management of TEF may be a save option in patients with uncomplicated ventilation and moderate and nonprogressive emphysema.
Challenges and Opportunities in Cardiovascular Surgery
Challenges and Opportunities in Cardiovascular Surgery
Groeben, H., Schulze, L., Brunkhorst, V., Alesina, P. F., & Walz, M. K. (2021)
Abstract
Background: During resections of phaeochromocytoma release of catecholamines can lead to excessive hypertension and arrhythmia. Therefore, these procedures can be stressful to surgeons and anaesthetists. It is completely unknown, how the excessive catecholamine concentrations in phaeochromocytoma patients relate to catecholamine concentrations of physiological stress of physicians and control patients undergoing adrenalectomy because of hormone inactive tumours. We measured catecholamine concentrations, heart rate and blood pressure in patients with phaeochromocytoma, incidentaloma, a surgeon and an anaesthetist.
Methods: After approval of the local ethics committee, we measured metanephrine and normetanephrine plasma concentrations in 8 patients with phaeochromocytoma, 6 control patients with incidentaloma, one surgeon and one anaesthetist at rest, after incision, after 20 and 40 minutes of surgery, and in recovery. Moreover, blood pressure and heart rate were obtained.
Results: Intraoperatively significant increases of blood pressure, metanephrine and normetanephrine were found in patients and surgeon. Significant increase of normetanephrine was also found in control patients. But catecholamine concentrations in patients with phaeochromocytoma were 18 to 42 times higher than in control patients and physicians. Heart rate analysis showed no significant results.
Conclusion: During phaeochromocytoma resections significant increases in catecholamine concentration and blood pressure can be found in patients and physicians. The excessive increase of catecholamine concentrations in phaeochromocytoma patients, was not always reflected by a corresponding blood pressure increase. Interestingly, although catecholamine concentrations in phaeochromocytoma patients almost normalize directly after surgery, their blood pressure remains stable without the need for pharmacological support.
Razi, A. a. M. (2023)
Abstract
Robotic surgery is a platform for minimally invasive thoracic surgery with similar general advantages as in VATS (Video Assisted Thoracic Surgery) including small incisions, faster recovery, minimal blood loss and shorter hospital stay. The extra advantages of using a robotic platform in thoracic surgery include a three-dimensional surgical view, elimination of physiological tremors, and enabling surgical manipulation in a natural orientation because of the presence of forceps that move in the same manner as human wrist joints. These advantages allow more complex procedures to be performed safely and easier technically, thus leading to better outcomes and improvement in the overall result. As a new advance in thoracic surgery, it has challenges that may become the reason why this technique has difficulty being adopted by a number of surgeons including cost, advancement in VATS technique and instrumentation. Despite the challenges, robotic thoracic surgery offers the platform for the expansion and improvement of thoracic surgery. Development in instrument technologies and designs, in addition to progress and interest in other futuristic technology, are notable opportunities for thoracic robotic surgery.
Berivan Bedir Sert, M.D., Mahmut Yargı, M.D., Mehmet Ferit Özdemir, M.D., Meral Erdal Erbatur, M.D., Tuba İlhan Karaaslan, M.D., and Osman Uzundere, M.D. (2024)
Abstract
Background: Intraoperative hypertension continues to be a significant cause of morbidity and mortality for patients undergoing surgery. In this case presentation, an instance of sudden, unexpected, and resistant hypertension during surgery will be discussed in a patient who underwent mitral valve replacement.
Case report: A 75-year-old patient with known coronary artery disease and advanced mitral stenosis underwent mitral valve replacement surgery. During the intraoperative process, after the completion of cannulation procedures and transitioning to partial bypass, a sudden increase in blood pressure was observed in the patient. Blood pressure was only brought under control through the intravenous administration of a triple antihypertensive agent. Upon postoperative evaluation following a smooth completion of the surgery and discharge, findings suggested that the cause of the hypertension in the patient might be renovascular hypertension.
Conclusions: Intraoperative hypertension, when unexpected and sudden, can lead to an increase in mortality and morbidity. During the intraoperative process, efforts should be made to identify the underlying causes promptly, and appropriate interventions should be carried out. In the postoperative period, patients should be thoroughly evaluated for underlying reasons.
Evaluation of Common Clinical and Hemodynamic Parameters to Pulmonary Capillary Wedge Pressures in Patients Undergoing Right Heart Catheterization
Hocking, K. M., Huston, J., Schmeckpeper, J., Polcz, M., Case, M., Breed, M., Vaughn, L., Wervey, D., Brophy, C. M., Lindenfeld, J., & Alvis, B. D. (2022)
Abstract
Introduction: A cornerstone of heart failure assessment is the right heart catheterization and the pulmonary capillary wedge pressure measurement it can provide. Clinical and hemodynamic parameters such as weight and jugular venous distention are less invasive measures often used to diagnose, manage, and treat these patients. To date, there is little data looking at the association of these key parameters to measured pulmonary capillary wedge pressure (PCWP). This is a large, retrospective, secondary analysis of a right heart catheterization database comparing clinical and hemodynamic parameters against measured PCWP in heart failure patients.
Methods: A total of 538 subjects were included in this secondary analysis. Spearman’s Rho analysis of each clinical and hemodynamic variable was used to compare their association to the documented PCWP. Variables analyzed included weight, body mass index (BMI), jugular venous distention (JVD), creatinine, edema grade, right atrial pressure (RAP), pulmonary artery systolic pressure (PASP), systemic vascular resistance, pulmonary vascular resistance, cardiac output (thermal and Fick), systolic blood pressure, diastolic blood pressure, heart rate, respiratory rate, oxygen saturation (SpO2), and pulmonary artery diastolic pressure (PADP).
Results: Ten out of 17 selected parameters had a statistically significant association with measured PCWP values. PADP had the strongest association (0.73, p<0.0001), followed by RAP and PASP (0.69, p<0.0001 and 0.67, p<0.0001, respectively). Other significant parameters included weight (0.2, p<0.001), BMI (0.2, p<0.001), SpO2 (-0.17, p<0.0091), JVD (0.24, p<0.005) and edema grade (0.2, p<0.0001).
Conclusion: This retrospective analysis clarifies the associations of commonly used clinical and hemodynamic parameters to the clinically used gold standard for volume assessment in heart failure patients, PCWP.
Çelik, S., Çallı, İ., Deniz, S., Bartin, M., Çıkman, Ö., Duran, M., & Binici, S. (2022)
Abstract
World Health Organization defines obesity as “excessive fat accumulation at a level that may impair health”. Obesity is also officially defined as a “disease” by many surgical and endocrine societies (1,2), and also accepted as a risk factor for some cancers, cardiovascular diseases, chronic kidney disease, diabetes, metabolic syndrome, non-alcoholic fatty liver disease, as well as many chronic diseases (2). Although the degree of accuracy is debated, obesity is still defined as a body mass index (BMI) above 30 (1).
Obesity, which was alarming in western countries in the past, is currently a public health problem that concerns the whole world, except for a few southern African and Asian countries (1). Preventive measures are important in tackling the public health problem. In this context, an active life and low-calorie nutrition are accepted as basic preventive practices.
Bhamidipati, C. M., Morasch, A., Mitchell, B., Atkinson, T. M., Cannan, C. R., Gross, B. D., Ravichandran, P., Rahimtoola, A., Gluckman, T. J., & Chadderdon, S. (2020)
Abstract
The Sars-Cov-2 (COVID-19) pandemic has created unprecedented challenges, and revamped the way we live and work. Overall, this pandemic and its isolating consequences has forced societies to become more creative and develop new ways to engage. Professionally, employees are more secluded with attempts to work from home, while in the medical community, physicians have needed to either be on the frontlines treating patients or have adapted to interacting with patients virtually. Even with today’s technological advances to virtually connect with patients, physicians have had to relearn and re-engage.
Singh, F. (2020)
Abstract
Prostatectomy is associated with short- and long-term morbidity, which includes attenuation of cardiovascular and muscle function, as well as the deterioration of lean body mass. Physical function is a known predictor of morbidity and mortality, with initial evidence indicating that pre-surgical exercise is associated with fewer post-surgical complications and shorter hospitalisation. Prehabilitation has been previously shown to be more effective in enhancing postoperative functional capacity than rehabilitation alone. Evidence grows indicating benefits to clinical, physical and quality of life outcomes. Exercising within this critical period between cancer diagnosis and surgery allows the usage of surgical wait time to promote and facilitate health behaviour changes that can lead to altering prostate cancer patient management. By combining exercise with a nutritional and psychological intervention a prostate cancer patient can be set up to significantly improve preoperative physical and mental fitness in preparation for surgery and beyond.
Belerenian, G., Gabay, A., Hall, P. P. I., Pucheta, C., Bouquet, O., Linares, M., Rodríguez, D., & Abuin, G. (2023)
Abstract
The application of the Alfieri technique in humans is a well-known and pioneering thechnique that was replaced by modern atrioventricular valve repair strategies.1,2 This technique in canines and also in humans is yet a valid alternative, particullary to canine tricuspid dysplasia.1 The “strategy” consists to transform the “monorificial” dysplastic tricuspid valve insufficiency into a “biorificial” one by means of a suturing at the level of the valve apposition face in the site of greatest regurgitant flow. The surgical field is cleared from blood by means of occlusion of both venae cavae. With this strategy the reduction of the insufficiency jet was achieved in 7 canine carriers of said congenital pathology. The technique demonstrated its anatomical reliability, repeatability, low mortality, and low cost. Of the total number of cases operated on, one patient died the day after surgery, another patient a year later due to non-cardiac causes, and the rest continue under clinical follow-up at the time of presenting this series.
Dashek, R. J., Higashi, Y., Das, N. A., Russell, J. A., Martinez‐Lemus, L. A., Rector, R., & Chandrasekar, B. (2022)
Abstract
Aims: Chronic intermittent hypoxia (IH), a characteristic feature of obstructive sleep apnea (OSA), contributes to cardiovascular diseases, including atherosclerosis, potentially through persistent oxidative stress and inflammation. TRAF3IP2 (TRAF3 Interacting Protein 2) is an oxidative stress-responsive proinflammatory adapter molecule and plays a causal role in a preclinical model of atherosclerosis. Since SGLT2 (Sodium/Glucose Cotransporter 2) inhibitors have shown protective effects in CVD by inhibiting oxidative stress and inflammation, we hypothesized that IH promotes the crosstalk between oxidative stress and TRAF3IP2, resulting in IL-6-dependent human aortic smooth muscle cell (SMC) proliferation, and that these effects are inhibited by the SGLT2 inhibitor empagliflozin.
Materials and methods: Primary human aortic SMC were exposed to various cycles of IH. Normoxia served as a control. To understand the molecular mechanisms underlying IH-induced nitroxidative stress, TRAF3IP2 and IL-6 induction, and SMC proliferation and those targeted by empagliflozin were determined by treating SMC with various pharmacological inhibitors and viral vectors.
Results: IH upregulated TRAF3IP2 expression, TRAF3IP2-dependent superoxide, hydrogen peroxide and nitric oxide generation, NF-kB and HIF-1a activation, IL-6 induction, and SMC proliferation. Exposure to IL-6 by itself induced SMC proliferation in part via TRAF3IP2, IL-6R, gp130, JAK, and STAT3. Further, SMC express SGLT2 at basal conditions, and is upregulated by both IH and IL-6. Importantly, empagliflozin inhibited IH-induced TRAF3IP2 upregulation, reactive oxygen and nitrogen species generation, TRAF3IP2-dependent HIF-1a and NF-kB activation, IL-6 induction, and IL-6-dependent JAK-STAT3-mediated SMC proliferation. Moreover, empagliflozin inhibited IL-6-induced STAT3-dependent SMC proliferation.
Conclusions: These results suggest the therapeutic potential of empagliflozin in IH and inflammatory vascular proliferative diseases associated with OSA.
Van Ginkel, N., Meijer, D., Boormans, J. L., Mertens, L. S., Van Beek, S., & Vis, A. N. (2023)
Abstract
Introduction Radical cystectomy improves survival of patients with muscle invasive and high-risk non-muscle invasive bladder cancer, but is a challenging surgical procedure as patients may experience major complications after surgery.
Objectives To assess the incidence of Clavien-Dindo ≥3 complications in patients who underwent radical cystectomy and to assess the association of these complications with pre-operative and peroperative parameters. The secondary aim was to study the association of complications with long-term oncological outcome.
Methods A nationwide registry was set up in 19 Dutch hospitals that studied patients with muscle invasive bladder cancer and high-risk non-muscle invasive bladder cancer treated by radical cystectomy. Major complications were classified as complications that were related to uretero-ileal anastomosis, intra-abdominal (e.g. urinoma, bowel leakage) infectious and cardiovascular complications. Multivariable logistic regression analyses were performed to assess the correlation between these groups and perioperative, clinical and pathological factors. Kaplan-Meier survival curves were constructed to analyze the correlation between complications and overall survival.
Results The study population consisted of 1,464 patients, of whom 420 (29%) developed severe complications. The most common complications were intra-abdominal (n=328, 60%) and uretero-ileal anastomosis related (n=92, 17%). Male gender (odds ratio 1.6, p=0.007), American Society of Anaesthesiologists score ≥3 (odds ratio 1.6, p=0.003), Charlson Comorbidity Index score ≥5 (odds ratio 2.1, p=0.002) and blood loss >700ml (odds ratio 1.4, p=0.044) were associated with severe complications. In addition, open radical cystectomy was associated with multiple complications (odds ratio 2.6, p=0.001). Furthermore, the overall survival of patients with major complications was worse than those who had no major complications. The median overall survival was 3.8 years versus 6.2 years for patients with and without severe complications (p<0.001).
Conclusions In a real-world setting, 29% of patients undergoing radical cystectomy developed severe complications. The risk of severe complications was higher in men, patients with impaired pre-operative condition, and in those who underwent open surgery. Severe complications had a negative impact on overall survival.
Bono, L., Puente, L. J., Szarfer, J., Llobera, M. N., Doppler, E. M., Estrella, M. L., Kim, A., Mori, A. L., Arce, P., & Gagliardi, J. (2020)
Abstract
Background
Single and multi-center studies have described substantial changes in the landscape of health care in cardiac intensive care units (CICU). Few reports have quantitatively characterized current diagnoses in a contemporary CICU in Latin America.
This study aims to describe demographics, diagnoses, care patterns, and outcomes in patients admitted to a CICU in a high-volume center in South America.
Methods
A total of 1629 consecutive patients admitted to CICU from December 2017 to April 2020 were included in a prospective registry. The variables analyzed included demographic data, admission and final diagnoses, management, and outcomes.
Results
Among 1629 participants, 32.4% were women, and the median age was 62 years (53-71). Admissions were due to primary cardiac causes in 1335 (81.9%), postsurgical care in 13.3%, and a combination of general and cardiac diagnoses in 4.8% of patients. The most frequent diagnosis on admission was acute coronary syndrome (ACS) (35.7%). Primary reasons for CICU admission were postprocedural observation (PPO) (31.8%), diagnosed or suspected ACS (31.7%), heart failure (10.1%), postsurgical management after cardiovascular surgery (8.9%), arrhythmia (5.8%), shock (4.5%) and cardiac arrest (CA) (1.2%). Advanced CICU therapy requirements were ventilatory assistance (19.3%) and vasoactive or inotropic drug use (19.6%). The overall mortality rate was 6.4%. Admission diagnoses associated with the highest mortality rates were CA (52.6%), noncardiogenic shock (39.5%), and cardiogenic shock (32.3%). Notably, patients admitted solely for PPO had a mortality rate of 0.8%.
Conclusions
In a contemporary CICU from a high-volume reference center in South America, the most frequent diagnosis was an ACS, although it represented only one-third of the admissions.
One-fifth of admissions required advanced CICU therapies. CA and shock on admission carried a poor prognosis. We identified PPO as a substantially low-risk population.
Kalaycı, T. Ö., Sönmezgöz, F., & Kestellı, M. (2023)
Abstract
Aims: The purpose of this study was comparing flow volume rates, velocities and diameters of lower extremity arteries and veins of smokers and non-smokers with peripheral arterial disease.
Patients and methods: The study consisted of 58 patients, 26 smokers and 32 non-smokers, who had no smoked for at least 5 years prior to the investigation. Colour Duplex Ultrasonography measurements of the common femoral artery, common femoral vein, popliteal artery, popliteal vein, anterior tibial artery, anterior tibial vein, posterior tibial artery and posterior tibial vein were obtained in the supine position. Differences in the diameters, blood flow velocities, and flow volume rates of the vessels were compared according to the sex, age and Colour Duplex Ultrasonography measurements of the patients.
Results: The diameters of the common femoral artery, popliteal vein and posterior tibial artery were statistically significantly reduced in smokers. The flow volume rate of the popliteal artery showed a significant correlation with that of crural vessels in non-smokers but not in smokers.
Conclusions: The absence of a statistically significant correlation between the measurements of the popliteal artery and crural vessels in smokers shows that cigarette smoking reduces the diameters and flow volumes of crural vessels, potentially giving rise to impaired tissue perfusion.
Compagnucci, P., & Capucci, A. (2019)
Abstract
For the past 10 years, the introduction of rivaroxaban in clinical practice has produced dramatic changes in lives of patients affected by thrombotic disorders. In this review, we discuss rivaroxaban’s pharmacokinetic properties, focusing on the issues of interactions with other drugs and on the appropriate clinical use of coagulation tests in patients treated with this drug. We also examine the many clinical scenarios in which rivaroxaban was tested. In particular, results of studies on venous thromboembolism (VTE) prevention in orthopaedic surgery, deep vein thrombosis (DVT) and pulmonary embolism (PE) acute and long-term treatment with a focus on cancer patients, stroke prevention in atrial fibrillation (AF) with a special mention for cardioversion and trans-catheter ablation and atherosclerotic cardiovascular disease are presented. Our objective is to provide a summary of the evidence in order for the physician to be able to critically apply this information to patients’ management in everyday clinical practice.
Challenges and Opportunities in Asthma
Challenges and Opportunities in Asthma
Daria Lahoda
Abstract
Diseases of the respiratory tract occupy one of the leading places among pathologies in people of working age in the world. According to the data of world studies, it can be considered that these two comorbidities are mutually aggravating, but scientists do not have a unanimous opinion about whether this is a simple coincidence or whether these pathologies are pathogenetically related. There is considerable evidence that asthma patients do not achieve adequate asthma control worldwide. Yes, according to Maria Sandra Magnoni et al. 77.8% of patients with asthma have an uncontrolled course of asthma, although 68.4% of them believe that they have sufficient asthma control, and their treatment does not require correction. Therefore, taking into account all of the above and taking into account the low level of asthma control in patients with comorbid pathology who often suffer from bacterial and viral diseases, we believe that a more detailed study of the immunological status of these individuals is necessary in order to optimize treatment and prevention measures. Aim: to investigate the effectiveness of alternative ways of asthma control in patients with bronchial asthma against the background of overweight or obesity. Materials and methods. At the I stage, 255 patients with BA were examined. According to the study design, patients were selected according to the “inclusion/exclusion” criteria at this stage. The study was randomized. Allocation of patients into groups was carried out by the method of simple randomization with elements of stratification. Groups are statistically significant. Statistical processing of the results was carried out using parametric and non-parametric analysis methods. Resalts. Overweight or obese patients had a more severe course of bronchial asthma than patients with a normal body mass index. Overweight or obese patients were found to have higher levels of systemic inflammation, namely eosinophilic cationic protein levels and erythrocyte sedimentation rate, than patients with a normal body mass index. In addition, a close direct correlation was established between the severity of the course of bronchial asthma and indicators of eosinophil cationic protein (r=0.97; p˂0.001). After pharmacological correction, there was an increase in asthma control in patients with different severity of the course (р˂0.001; p˂0.001; p˂0.001, respectively), a decrease in the frequency of exacerbations (p˂0.05), a reduction in the number of hospitalizations (p˂0, 05) and the number of acute respiratory diseases (p˂0.05) in patients with bronchial asthma against the background of excess body weight or obesity. The use of the developed treatment-prophylactic complex using the drug bacterial lysate and inosine pranobex together with training in the Asthma School and standard treatment contributes to increasing asthma control and compliance with the doctor, reducing the number of exacerbations and hospitalizations per year in patients with bronchial asthma against the background overweight or obesity.
Guadalupe García Elorriaga, Maximino Miranda-García, Guillermo Del Rey-Pineda, Luisa María Sánchez-Zamorano, Eduardo César Lazcano-Ponce, and Eduardo Salazar-Martínez
Abstract
Previous report shows relationship between C. pneumonie and Asthma. In this study, we assessed the association between exposure to C. pneumoniae infection and the risk of bronchial asthma in adolescents in the State of Morelos, Mexico. An analysis was performed on a population-based cohort study of 80 adolescents with respiratory symptoms of asthma defined by ISAAC and 202 healthy adolescents between 12 and 17 years old. The information was collected twice from questionnaires, anthropometry, and sampling. Excessive weight gain was determined by calculating body mass index, and exposure to the specific antibodies IgM, IgG, and IgA was detected by microimmunofluorescence. The geometric means were calculated for titers of C. pneumoniae. The odds ratio was used across multiple models. The results showed that the exposure to C. pneumoniae was very high in the study population (67.2%). All immunoglobulins were significantly increased in patients with asthma symptoms compared with the healthy population (17% for IgG, 34% for IgM, and 52% for IgA). In multiple models, the IgM and IgA immunoglobulins were found to be associated with asthma (OR, 2.4; 95% CI, 1.4–4.2 and OR, 2.4; 95% CI, 1.2–4.8, respectively). Our study reflects a high seroprevalence of C. pneumoniae in the population; this seroprevalence is higher in young people with asthma. Specific immunoglobulins to C. pneumoniae are associated with IgM and IgA. The epidemiological significance of our results influences the timely monitoring and management of infections acquired at an early age that persist, or recur, for much of the juvenile life. Additional studies are needed to validate our findings.
Yousser Mohammad, MD, PhD and Basim Dubaybo
Abstract
The Global Asthma Network (GAN) report issued in 2022 and the Global Initiative for Asthma (GINA) report of 2023 emphasize challenges and difficulties faced by health workers in managing asthma in Low- and Middle-income countries (LMICs). Among the many reasons for these difficulties are insufficient knowledge of health workers of management guidelines, and lack of medical resources especially inhaler medications1,2,3. When available in limited amounts, these resources are prohibitively expensive4,5,6. These reports did not address the impact of disaster on asthma care. In this article, we aim to highlight this issue, hoping that future international asthma reports will take this aspect into consideration.
When disasters such as war and earthquakes occur in LMIC, several aspects of asthma care are negatively impacted. First, challenges in asthma management are compounded by difficulties related to displacement, overcrowding in shelters, immigration of health care workers (HCW), damage to health facilities, limited referral capacity to specialists, and limited availability of expensive inhalers4,5,6. Second, governments face logistical challenges. While the immediate need may be to provide emergency needs,6,7 health facilities should secure medications to provide care according to World Health Organization (WHO) guidelines7. Third, asthma research and data collection are hampered.8 Digital health could be a solution9,10.
It is therefore imperative that we develop suitable asthma management programs applicable to zones in turmoil4,11,12.
We conducted a literature search on challenges in asthma management in zones of turmoil. We used the following search keywords and phrases: asthma and war, asthma and turmoil, asthma and earthquakes, and asthma and disasters. We reviewed all publications that relate to this topic that appeared in the literature between 2014 and 2023. Based on this review and analysis, we list several lessons learned, conclusions and recommendations.
Razia Sultana Mansoor Ghani, Ann Smith, Shazia Ashraf, and Shakeela Bashir
Abstract
Background: Bronchial sensitive individuals are prone to develop many health issues from airborne allergens, and viral and bacterial respiratory infections. Studies have shown that airborne allergen causes allergies and asthma in the susceptible population. Some other environmental factors such as tobacco smoke, air pollution and diet have also been linked to an increased risk for the onset of asthma. The burden of asthma is increasing day by day but the exact etiology of asthma is yet unknown. Some genetic predisposition and environmental factors are thought to play a role in causation of disease, yet how they interact to cause asthma it is still being investigated.
Methods & Study Design: A Cross- sectional analytical study design was used to determine the various environmental factors that can trigger asthma and their association with asthma control among school aged asthmatic children, 4-12 years age. A questionnaire was used to find out various environmental factors that can trigger asthma attacks. Data was represented in the form of tables and the chi square test was used to determine the association of various environmental factors with asthma control.
Results: A total of 196 asthmatic children and their parents participated in this study. The chi-square test showed that female parents control asthma more effectively as compared to male parents. The majority of parents 118 (60.2%) were living in urban areas, 180 (91.8%) parents had low income adequacy level, 119 (60.7%) parents’ homes had 1-2 rooms, and 118 (60.2%) homes were congested/poor ventilated. Environmental factors had a direct link with asthma. Children exposure to passive-smoking 106 (54.08%), exercise (p =.035*), sports (p =.015*), cold weather (p =.002*), seasonal allergy (p =.002*), allergic rhinitis (p =.004*), small homes (p =.008*) and, uneducated parents (no education or primary only) (p =.035*) are factors that are associated with high asthma rates.
Conclusion: Asthma is influenced by environmental factors. By modifying environmental factors, we can improve the number of asthma episodes among asthmatic children.
MUHAMMED ANAS AYOOB, Soumya Mol Mohammed Ismail, and Dr. Prasad
Abstract
Background: The most crucial step in achieving and keeping asthma under control is to lessen the inflammation in the airways. Nitric oxide fractional exhaled (FeNO) levels have been utilised as an indicator of airway inflammation. Uncertainty regarding the potential function and properties of exhaled fractional nitric oxide in asthma management.
Objective: To determine whether FeNO and Asthma Control Test (ACT) can objectively assess asthma control in adult patients and identify any potential relationships between FeNO and both the ACT score and the spirometry data of patients. Also determine their use in reducing the dose of inhaled steroids.
Methods: The design of the study was a systematic review. A qualitative research methodology based on an analysis of previously published materials.
Results: This study thoroughly examined the literature on the Asthma Control Test and Fractional Exhaled Nitric Oxide assessment of asthma control in adult patients. Finally, 16 scientific studies were analysed. The highest variations in FeNO values during diagnosis were significantly linked with FeNO levels at diagnosis during conventional asthma treatment. Evaluating adherence and FeNO response to monitored inhaled corticosteroid treatment may prevent the needless progression to biologic therapy in asthmatic patients with high Type-2 biomarker levels. There is a close connection between the ACT score and the treatment modifications as well as the measurements of lung function. FeNO may be able to detect poor asthma control; however, it cannot substitute for clinical judgment and may only be beneficial in a subset of asthmatics. The average and percentage variation of standards following asthma treatment did not show any significant relationship between FeNO levels and various other factors are related (expiratory volume in one second (FEV1) or ACT scoring), however, there were strong positive correlations between ACT scores and FEV1.
Conclusion: Research revealed a highly significant link between the level of FeNO at diagnosis and the biggest variations in FeNO readings after diagnosis. Using FeNO as a supplementary non-invasive method for assessing asthma control may be effective in both steroid-naive asthmatics and those who are being treated with steroids.
Tassalapa Daengsuwan, MD and Thitaya Sangsawang, MD
Abstract
Background: Monitoring of lung function is necessary to detect irreversible airway obstruction in both asthma and obesity. Impulse oscillometry (IOS), a novo non-invasive equipment, is increasing popularity to measure airway resistance in young children worldwide.
Aims: To compare IOS parameters among Thai asthmatic children and Thai obese children with and without asthma.
Methods: A cross-sectional study was conducted in 120 participants, aged 4-15 years old. Forty children were in each group (asthma, obesity, and obesity with asthma). All volunteers were consented to measure airway resistance by IOS technique (Jaeger, Germany).
Results: Seventy-three percent of patients were male with the mean age at 8.8 + 2.61 years old. Mean X5 was found normal in childhood obesity (-0.13) when compared to children with asthma (-0.23) and obesity with asthma (-0.19) (p < 0.001 and 0.013 respectively). The cut-off value of X5, according to ROC curve, for predicting asthma in obese patients was -0.16 kPa/L/s with 70% sensitivity, 70% specificity and 70% accuracy (AUC= 0.69). However, with the bronchodilator effect (adjusted by duration of asthma control), we found significant higher percentage change of IOS parameters, including resonant frequency, area of reactance and R5-R20, in asthma (Fres -24.57 + 15.82, AX -58.28 + 13.37, R5-R20 -51.32 + 20.13) than in asthma with obesity (Fres -13.77 + 16.42, AX -43.35 + 21.4, R5-R20 -34.72 + 18.21), (p = 0.014, 0.004, 0.002 respectively).
Conclusions: X5 and percentage changes after bronchodilator of Fres, AX, and R5-R20 are useful parameters to differentiate airway dysfunction in asthmatic children from obese children.
Matti Korppi
Abstract
The risk of asthma and lung function reduction is increased in children who have presented with wheezing associated with respiratory tract infection in early childhood. Three prospective cohort studies consisting of patients hospitalized for infection-associated wheezing at <24 months of age, which started in Finland and Sweden in the 1980`s and 1990`s, have reported outcomes at >25 years of age. These three cohorts are even globally the only cohorts consisting of early-childhood wheezers followed prospectively until adulthood. Initially, the studies were not controlled, and the risk of asthma and reduced lung function and the risk factors in question were assessed by analyses within the cohorts. Matched population-based controls without wheezing history in early childhood were recruited for the studies in adulthood. One follow-up included only questionnaire data without lung function results. Two studies included control visits, and one of them presented clinical and lung function data, and the other clinical and bronchial reactivity data. Respiratory syncytial virus was identified on admission in all three post-wheezing cohorts, and rhinoviruses in the newest cohort from the 1990`s.
The present narrative review summarizes data on asthma and lung function reduction in adults aged >25 years after hospitalization for wheezing at age <24 months compared to population-based controls in the three until now published prospective post-wheezing cohorts. The frequency of doctor-diagnosed asthma varied from 10.3% to 36.6%, and that of self-reported symptom-based asthma from 35.4% to 40.7%. The differences between cases and controls were significant and robust to adjustments with current smoking and allergic rhinitis, which were associated with asthma in all cohorts. One cohort study reported lung function results, and both baseline and post-bronchodilator forced expiratory volumes were lower in cases than in controls. About 10-15% of former early-childhood wheezers presented with irreversible lung function reduction characteristic to chronic obstructive lung disease. Family asthma was associated with current asthma, but other early risk factors, with exception of blood eosinophilia in one cohort, were not anymore predictive.
In conclusion, hospitalization for infection-associated wheezing at <24 months of age was an independently significant risk factor of asthma in adults at >25 years of age.
Oishi Sikdar and Anne Greenough
Abstract
Sickle Cell Disease is a life-threatening hereditary blood disorder which affects millions of people worldwide. Pulmonary complications are important causes of morbidity and mortality in patients with sickle cell disease. Asthma is a recognised comorbidity of sickle cell disease and may occur in between 15 and 28% of children with sickle cell disease. It has been associated with increased episodes of acute chest syndrome and all cause mortality. Obstructive lung disease, however, is common in children with sickle cell disease, independent of an asthma diagnosis. This review explores the pathophysiology, diagnosis and therapeutic opportunities for asthma in sickle cell disease patients. The diagnostic challenges and inconsistencies in current clinical approaches are highlighted. Convergence of inflammatory pathways in sickle cell disease and asthma occurs, but there is also a heightened level of inflammation unique to sickle cell disease. Thus, wheezing may not be due to asthma but be a manifestation of sickle cell disease per se and the result of the increased pulmonary vascular volume. As a consequence, anti-asthma therapy may not be appropriate for all wheezy children with sickle cell disease and commencing treatment on the basis of a physician’s diagnosis alone is inappropriate. Data from paediatric cohorts suggest use of spirometry, aeroallergen sensitisation tests, impulse oscillometry and dedicated interdisciplinary pulmonary clinics could improve diagnosis accuracy. Corticosteroids and bronchodilators are well-established treatments for asthma; observational studies suggest they may provide benefit for some children with sickle cell disease, but therapies such as hydroxyurea may improve respiratory outcomes in others. It is, therefore, essential children are thoroughly investigated and followed-up and a personalised approach taken to their care. Prospective randomised studies are required to establish the effectiveness of asthma therapies in children with sickle cell disease.
Tassalapa Daengsuwan and On-anong Nilwalaikul
Abstract
Background: Impulse oscillometry (IOS), a new respiratory impedance measurement, is increasing in its popularity as a means to assess airway resistance in young children. Its great advantage lies in its effortless and fast performance, making the airway obstruction measurement easier for patients who are not able to perform spirometry tests. However, studies comparing spirometry with IOS in Thai children are rare.
Aims: To evaluate the correlation between IOS and spirometry parameters in Thai childhood asthma
Methods: Vyntus IOS (JEAGER®, Germany) and spirometry tests (Vyntus SPIRO) were performed in 48 children, aged 5-15 years old, who fulfilled the GINA asthma criteria. The study, approved by the hospital’s ethics committee, was conducted between March 1, 2020 and March 31, 2021 at the Queen Sirikit National Institute of Child Health, Thailand. (TCTR20220527005)
Results: Forty-eight childhood asthma patients with a median age of 10.79 (IQR = 8.41, 11.87) years underwent both IOS and spirometry measurements. Male sex was predominant (64.58%), and 77% of patients had well-controlled asthma (C-ACT score ≥20). In our study population, the atopic comorbidities were allergic rhinitis (91.67%), atopic dermatitis (10.42%) and food allergy (10.42%). Moreover, parental asthma was found in 16.67% of the participants. In comparison with spirometry, the percentage change of FEF25-75% was significantly negatively correlated with R5, R10, AX, and mean R5-R20 (r = -0.608, -0.528, -0.500, -0.511, respectively; p <0.001). Likewise, FEV1 was significantly negatively correlated with R15 and R20 (r = -0.520, -0.565, respectively; p <0.001). The linear regression prediction model demonstrated that a 30% increase in FEF25-75% was related to a 22.7% reduction in R5 (p = 0.007).
Conclusion: The percentage change of FEF25-75% was found to negatively correlate in statistically significant terms with R5 in Thai childhood asthma. Hence, IOS is an effective and feasible replacement for spirometry as a measurement modality of lung function, especially in young children.
Angelica Gangemi, Nabil Abou-Baker, and Kristin Wong
Abstract
Purpose: This study examines the correlation of the Mini Pediatric Asthma Quality of Life Questionnaire (miniPAQLQ) with the Got Transitions Readiness Assessment Survey (GTRAS) of inner-city adolescents and young adults with asthma in Newark, New Jersey.
Methods: One hundred six patients with asthma, aged 12-21 years old, were assessed at University Hospital in Newark, NJ while receiving typical care. In this cross-sectional study, patients were assessed using the miniPAQLQ and GTRAS tools. General demographics were captured. MiniPAQLQ sections on activity, symptom, and emotional function, were compared to the GTRAS questions on perceived transition readiness and ability to complete healthcare tasks
Results: Fifty-three percent of the patients were female, 57% were African American, 37% were Latino/a, and 97% had insurance. The overall median quality of life (QOL) score was 6. Specific activity, symptom and emotional function QOL scores did not correlate with overall perceived transition readiness. However, QOL scores >5 did correlate with patients’ abilities to complete specific health-related tasks of transition, especially when comparing emotional function and “knowing” their health.
Conclusions: Our results demonstrate that the emotional function of adolescents and young adults with asthma is significantly linked to their ability to complete healthcare tasks independently, indicating that a psychological-based approach to transition may be necessary. Low emotional QOL scores may help identify patients at risk of poor transition who would benefit from additional intervention. Further research is needed to assess quality of life and its effects on development of these patients.
González-Uribe, V., Martínez-Tenopala, R., Baro-Alvarez, P., & Mojica-Gonzalez, Z. S. (2022).
Abstract
Background: Asthma is a chronic allergic disease characterized by variable airflow limitation; Obesity is a chronic disease that has reached epidemic proportions globally. Both are diseases with a significant inflammatory component, and their relationship suggests being weight dependent. Adiponectin (ADIPOQ) is the main adipokine secreted by white adipose tissue, it is an insulin synthesizer and regulator of energy homeostasis, and its plasma levels are inversely correlated with obesity and asthma. The effect of genetic factors in both diseases has been investigated, and haplotypes of the ADIPOQ 45 T/G (rs2241766) and ADIPOQ 276 G/T (rs1501299) polymorphisms have been related.
Aims: To know de polymorphisms frequency of ADIPOQ 45 and ADIPO 276 in obese and eutrophic adolescents with and without asthma, likewise, link the adiponectin levels with the presence of such polymorphisms.
Methods: An observational, analytical, and cross-sectional study in which 169 Mexican adolescents were recruited. Thirty mL of blood was taken from each individual; genomic DNA was extracted using the saline expulsion technique and quantified by spectrophotometry; two polymorphisms located in the promoter region were studied: ADIPOQ 45 and ADIPOQ 276; the determination of the different polymorphisms was carried out using TaqMan probes using real-time PCR (qPCR) using the commercial kit TaqMan One Step RT-PCR mastermix, the RNA extraction was carried out with Trizol Ls (Invitrogen), and the fluorescence was quantified employing the 7900HT ABI PRISM real-time computer SDS software.
Results: There were no statistically significant differences between ADIPOQ 276 and ADIPOQ 45 polymorphisms in asthmatic and obese patients. Compared to the control group, a negative correlation was observed between adiponectin plasmatic levels in obese and asthmatic individuals.
Conclusion: The ADIPOQ 276 and ADIPOQ 45 polymorphisms do not seem to be associated with asthma and obesity in the Mexican population. It is necessary to continue studying these polymorphisms and consider larger populations.
Feng, D. (2022).
Abstract
Yokkaichi asthma is one of Japan’s four “big pollution diseases.” It occurred in the early 1960s and was caused by emissions from the petrochemical industry. The disease led to the first litigation concerning air pollution in Japan. From 1967 to 1972, citizens fought against corporations as part of the Yokkaichi lawsuit. This article explores how Yokkaichi asthma occurred, how citizens saw the disease before and during the lawsuit, and what actions they took to react to the problem. By appealing, studying, recording, and measuring, citizens in Yokkaichi made their voices heard and helped scientists testify during the legal proceedings, ultimately promoting Japan’s environmental legislation.
Visser, R. (2016).
Abstract
Exercise induced bronchoconstriction (EIB) is a frequent and specific symptom of childhood asthma featured by expiratory flow limitation. A recent study showed that exercise can also induce inspiratory flow limitation, independent of EIB. The aim of this study was to investigate whether salbutamol protects against exercise induced inspiratory flow limitation in asthmatic children.
Methods: The study had a prospective double-blind placebo-controlled randomized cross-over design with two exercise challenge tests preceded by the inhalation of 200µg salbutamol or placebo. Children 8-16 years old with documented exercise induced inspiratory flow limitation performed two exercise challenge tests (ECT’s) to assess EIB. EIB was defined as a fall in forced expiratory volume in 1 second (FEV1) ≥ 13% whereas inspiratory flow limitation was defined as a fall in mid inspiratory flow (MIF50) ≥ 25%.
Results: 63% of the children (19/30) with exercise induced flow limitation showed an inspiratory flow limitation. Salbutamol significantly reduced the mean exercise induced fall in MIF50 in children with exercise induced inspiratory flow limitation compared to placebo (17.6% versus 24.9%, p=0.004).
Conclusions: We observed a significant but inconsistent, individually variable protection of salbutamol against exercise induced inspiratory flow limitation in contrast to the consistent protective effect of salbutamol against EIB. We confirmed that a substantial number of the children with exercise induced flow limitation have an inspiratory flow limitation. Asthmatic children who experience persistent exercise induced asthmatic symptoms despite the use of (prophylactic) salbutamol, may suffer from an inspiratory flow limitation as a component of their asthma.
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Nagasaka, Y., & Tsuchiya, M. (2021).
Abstract
Since the historical article by Forgacs in 1978, many studies have clarified the changes of lung sounds due to airway narrowing as well as the mechanism of genesis of these sounds. Studies using bronchoprovocation have shown that an increase of the frequency and/or intensity of lung sounds was a common finding of airway narrowing and correlated well with lung function in bronchial asthma. Bronchoprovocation studies also showed that wheezing may not be as sensitive as changes in basic lung sounds in acute airway narrowing in adult asthmatics.
In lung sound analysis, narrow airways cause an increase in the frequency of breath sounds and lung sound intensity, implying when the patient has higher than normal breath sounds, i.e., bronchial sounds, he or she may have airway narrowing. Recent studies reported that this increase of breath sounds suggested worsening of airway inflammation in rather stable patients with bronchial asthma. As it is difficult to detect subtle changes in lung sounds by auscultation alone, automated sound analysis will be expected.
Galvis, J., Villanueva, S., Mollinedo, M., Vázquez, M. F., Rodríguez, M., Vera, E., Álvarez-Leire, G., Lifona, L., Bacaicoa, M., Paez, A., Rodilla, E., Daga, Ó., Quintero, O., Capilla, M. R., Lorenzo, I., López, B. S., & Cancelliere, N. (2023).
Abstract
BACKGROUND: More than 90% of the Spanish population has been vaccinated against the SARS-CoV-2 virus in our setting. The administration of this vaccine is not contraindicated in allergic subjects; however, it is unknown whether any precaution should be taken when initiating subcutaneous allergen immunotherapy after this vaccination.
The objective of the study was to analyze the safety of subcutaneous allergen immunotherapy during the dose escalation phase in subjects sensitized to pollens or mites previously vaccinated against SARS-CoV-2.
METHODS: An observational study with retrospective data collection from protocolled patients’ medical records was designed. Outpatients older than 12 years with diagnosis of pollen or house dust mite allergic rhinitis with or without bronchial allergic asthma were selected who had completed the subcutaneous immunotherapy dose escalation phase. A complete SARS-CoV-2 vaccination was required for the inclusion.
RESULTS: Three hundred and seventy-nine patients were included by 53 investigators. The mean age was 31 years old and 55,9% female. Time from last SARS-Cov-2 vaccination dose to subcutaneous immunotherapy initiation was 4.1 months (95%CI 3.8-4.4). subcutaneous immunotherapy with a pollen allergoid was administered to 135 patients (35.6%) with a total of 739 injections, while subcutaneous immunotherapy using a house dust mite allergoid was administered to 244 patients (64.4%) with a total of 1311 doses. During the dose escalation phase with the pollen allergoid, 45 patients (33.3%) suffered 93 local adverse reactions (12.6% of injections), while 17 patients (12.6%) experienced 17 systemic allergic reactions (2.3% of injections) of them 14 were World Allergy Organization Grade 1 and 3 of Grade 2. During the dose escalation phase with the house dust mite allergoid, 55 patients (22.5%) reported 133 local adverse reactions (10.1% of injections), and 7 patients (2.9%) showed 7 World Allergy Organization Grade 1 systemic reactions (0.5% of injections). No systemic reactions Grade 3 or higher were reported.
CONCLUSIONS: The well-known safety profile of the subcutaneous allergen immunotherapy using pollen or house dust mite allergoids has not been changed after the SARS-CoV-2 vaccine administration. No relevant differences in the incidence of local or systemic allergic reactions during the dose escalation phase were identified, so it is considered that the patient’s safety has not been compromised to initiate this treatment after the SARS-CoV-2 vaccine administration.
Challenges and Opportunities in Arthritis
Challenges and Opportunities in Arthritis
Bjorg Gudjonsdottir, Audur Kristjansdottir, Svanhildur Arna Oskarsdottir, Judith Amalia Gudmundsdottir, Solrun W Kamban, Zinajda Alomerovic Licina, and Drifa Bjork Gudmundsdottir
Abstract
Purpose: To compare physical activity in children with juvenile idiopathic arthritis and age-matched peers.
Materials and methods: Daily physical activity was measured for seven consecutive days with activPALTM accelerometer in 8–18- year-old children with juvenile idiopathic arthritis (n=28) and age- and sex-matched controls (n=35). The main variables were daily steps and duration of time in moderate to vigorous physical activity. A mixed model analysis of variance was used for statistical analysis.
Results: The groups were comparable in terms of age, height, weight, body mass index and sex ratio. There was no difference in physical activity between the groups, measured in daily steps (p = 0.83) and duration of time in moderate to vigorous physical activity (p = 0.92). Both groups had lower physical activity at weekends than weekdays (p < 0.001). No interaction was observed between groups and days of the week regarding daily steps (p = 0.89) and time spent in moderate to vigorous physical activity (p = 0.60). Neither group met the current physical activity recommendations.
Conclusion: Physical activity of children with juvenile idiopathic arthritis in Iceland is comparable to age-matched peers without juvenile idiopathic arthritis. There is a need for intervention to increase physical activity in both groups.
Dr. Balaji Zacharia, Dr. Sanoj Poulose, Dr. Rose Xavier, Dr. Navaneeth Panarukandy, and Nidhin Chacko Valiyaveetil Hilary
Abstract
We report a case of Salmonella septic arthritis of the shoulder in an immunocompetent infant one month after COVID-19 infection. An eight-month-old infant presented with intermittent fever for two weeks. She had features of septic arthritis of the left shoulder. She was treated with arthrotomy of the shoulder. The Gram staining and culture were consistent with Salmonella. Ceftriaxone was given parenterally followed by an oral route. She recovered fully without any recurrence. Salmonella septic arthritis is a rare entity. This is the first case of Salmonella septic arthritis reported in an immunocompetent infant after COVID-19 infection.
Iulian Nusem and Marjoree Sehu
Abstract
Background: Septic arthritis of the hip is an orthopaedic emergency which requires prompt diagnosis and treatment. If treated late or inadequately, it can have devastating consequences for the development of the hip joint. Infection is most commonly caused by Staphylococcus aureus which spreads via the blood stream or from an adjacent area of osteomyelitis. Diagnosing and managing this condition continue to be challenging and poor outcomes may occur. Neonates may present with sepsis and failure to thrive. There may be no fever. The hip is held in flexed, abducted and externally rotated position. The limb is held still and any passive movement causes pain. Older children typically present with a limp or refusal to walk. Children typically have elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels. Needle aspiration is the most specific diagnostic test. Prompt surgical drainage and postoperative antibiotic therapy until signs of infection resolve are necessary to prevent late sequelae.
Objectives: The present review aims to discuss the published evidence related to the diagnosis of septic arthritis of the hip based on history, physical examination, laboratory tests, imaging studies and arthrocentesis, and management including antibiotic treatment and surgical joint debridement.
Conclusion: With prompt diagnosis and appropriate treatment, outcomes are generally good, with only few long-term sequelae. Delay in diagnosis and treatment may result in growth disturbances and joint destruction.
Dr. Balaji Zacharia, Dr. Sanoj Poulosse, Dr. Rose Xavier, Dr. Navaneeth Panarukandy, and Nidhin Chacko Valiyaveetil Hilary
Abstract
Salmonella infections of the bone and joints are very rare. They are common in hemoglobinopathies and immunocompromised children. The diaphysis and metaphysis of the long bones are common sites. The spine pelvis, ribs, and cranium are rare sites. The clinical course is indolent compared to acute osteomyelitis. Serological tests and culture can be used for the diagnosis. Radiographs are frequently negative early in the disease. CT scans and MRI scans can be used in certain cases. The majority of cases can be managed with antibiotics. In this review, we describe the etiology, clinical features, investigations, and management of Salmonella bone and joint infections. We have described the features of Salmonella bone and joint infections in normal and sickle disease patients. We also present an illustrative case of Salmonella septic arthritis of the shoulder in an immunocompetent infant one month after COVID-19 infection.
Abstract
Due to its remarkable mechanical properties and excellent biocompatibility, PyrocarbonTM is an ideal material for articular use. Various Pyrocarbon implants for the hand and wrist have been developed over the past 25 years. The Ensemble implant is unique in that it can be inserted as a minimally invasive hemiarthroplasty technique that does not require any preparation to insert a stem into the thumb metacarpal. The device has a unique three-dimensional design that locks onto the surface of the trapezium without requiring any internal fixation. We report on our first 12 cases with 1 year follow-up. There was significant improvement in the DASH score and pinch strength at 1 year follow-up (p< 0.5) with no significant decrease in thumb motion or instances of dislocation. One patient was revised due to rapid progression arthritis at the scaphoid trapezial interface that required revision to an arthroplasty with complete removal of the trapezium.
Abdulsatar J Mathkhor, Abdulnasser H Abdullah, Ali H Atwan, and Zahraa Mustafa Kamel
Abstract
Background: Levels of Vitamin D may impact the development and progression of knee osteoarthritis (OA), a disorder common in elderly people The aim of this study was to investigate the association between serum Vitamin D deficiency and knee OA.
Methods: One hundred twenty (40 male and 80 female) consecutive patients were recruited from the rheumatology outpatient clinic for the study. X-rays in two anterior-posterior and lateral views of the knees were performed for all patients. Staging of knee OA was done according to Kellgren-Lawrence criteria and divided into two groups; group A consisting of grades 1 and 2, and group B, consisting of grades 3 and 4. One hundred (30 male and 70 female) healthy individuals without clinical and radiographic signs of the disease were defined as a control group. Hematological and biochemical investigations, including measurement of 25-hydroxyvitamin D serum level, were performed for all participants. Pain intensity using a visual analog scale (VAS) and disease severity using the Western Ontario and McMaster Universities Arthritis Index was measured for all patients.
Results: The mean age of patients and controls were 60±3.5 and 54±2.6 years, respectively. Vitamin D levels of patients and controls were 13±3.3 and 32±2.5, respectively. More severe disease and diseases with prolonged duration were associated with a lower vitamin D level, and low vitamin D levels were associated with high VAS and WOMAC.
Conclusion: Vitamin D deficiency was associated with the development and the severity of knee OA as well as with the disease duration.
Spencer Lofink, B.S. and Thomas Trumble, M.D.
Abstract
We compared the effectiveness of Wharton’s jelly versus steroid injection into the carpometacarpophalangeal joint by comparing 60 patients in two cohorts with a follow up evaluation at three months and then at one year. We evaluated preoperative and postoperative grip strength, pinch strength, thumb range of motion, Disabilities of Arm, Shoulder, and Hand (DASH) score and a Visual Analog (VAS) pain score before the injection and then at 3 months and 12 months after injection. The patients in the steroid injection group had substantial improvement in their DASH and VAS pain scores as well as their pinch strength at 3 months p < .05. However, by the 12-month evaluation the benefits of the steroid injection had completely dissipated. The patients in the Wharton’s jelly cohort had improvements at 3 months in terms DASH and VAS score and pinch strength and this improvement persisted at the one-year evaluation. However, grip strength and thumb range of motion did not substantially improve in either group.
Challenges and Opportunities in Anesthesiology
Challenges and Opportunities in Anesthesiology
Aliaga, J., Ojeda, A., Comino-Trinidad, O., Cuñat, T., Arias, M., & Calvo, A. (2023).
Abstract
Introduction: The COVID-19 pandemic has resulted in a significant number of cases worldwide, leading to a substantial increase in Intensive care unit (ICU) admissions. Survivors of critical illness are known to experience long-term physical, cognitive, and psychological impairments. Chronic pain is also a prevalent complication, and specifically, neuropathic pain (NP) is strongly linked to a diminished quality of life. This narrative review aims to investigate the incidence, causes and manifestations of NP in critical illness COVID survivors.
Methods: A comprehensive search of the Pubmed database was conducted on May 31, 2023, using the keywords “Covid-19” OR “Sars-cov-2” combined with “neuropathic pain” and “critical care” OR “intensive care unit” to identify relevant publications in English or Spanish pertaining to adult human subjects. The search process adhered to the recommended flowchart format outlined in the PRISMA 2020 statement.
Results: The primary search yielded 26 results. Eight results were excluded as they did not pertain to COVID-19 pain.
Discussion: Intensive care survivors can develop new onset pain and chronic pain though various mechanisms. In the case of critical illness COVID-19 survivors, pain may arise due to viral neurotropic potential, immune-mediated reactions, and microvascular complications. Studies have reported new-onset upper extremity NP, with ulnar neuropathy being the most prevalent, followed by brachial plexus, axillary, and median neuropathies. Lower limb NP particularly sciatic neuropathy has also been documented, along with peroneal nerve, meralgia paresthetica, and femoral neuropathy. Cranial neuropathies, such as facial palsy and trigeminal neuralgia, have been observed in case series. Additionally, widespread pain frequently associated with critical illness neuromyopathy may be present. Notably, COVID-19 survivors with critical illness may experience nociplastic pain and conditions related to central sensitization, posing challenges in distinguishing them from those with Long-COVID syndrome.
Conclusion: Further research is crucial to gain a comprehensive understanding of the neurological consequences arising from critical COVID-19 illness. Healthcare professionals should maintain a high suspicion index for NP in this population. Advancing our knowledge of NP in COVID-19 survivors can help develop effective strategies to enhance overall patient outcomes.
Abstract
Anesthesiology is nowadays an independent and multidisciplinary speciality of great demand and responsibility and plays a preponderant role in the human life, from the moment of birth.
Anesthesiology has evolved since the earliest times to the present, along with the advances of science, intercepting most medical and surgical specialties, to the extent of being essential to us nowadays.
From the days of magic to the present time, the history of the speciality deserves to be visited.
This article of historical research provides a timeline review of the main themes and milestones of the specialty all over the world and particularly in Portugal, from ancient control of pain, the evolution of ressuscitation and critical care until the new technics and holistic care provided by modern Anesthesiology.
Zhang, J., Raines, D. E., Cogswell, L. P., & Strichartz, G. R. (2022).
Abstract
Binding of local anesthetics to plasma proteins has been presented as an important determinant of their bioavailability. Local anesthetics with a high potential for systemic toxicity, e.g. bupivacaine (BUP), are bound strongly by alpha1-acid glycoprotein (AAG), more weakly by serum albumin, but drug dissociation may be rapid, thus limiting the importance of protein binding. The purpose of this study was to determine the binding kinetics of BUP to AAG. Bupivacaine binding to AAG was monitored by its displacement of the fluorescent probe 1-anilinonaphthalene-8-sulfonic acid (ANS). The increased fluorescence of ANS (λ excit/em = 380/480 nm) upon binding to AAG was used to determine the equilibrium and kinetic characteristics of this reaction. By studying how BUP altered the binding kinetics of ANS to AAG it was possible to calculate the BUPs equilibrium and kinetic rate constants for AAG binding. ANS fluorescence increased ca. 50-fold when bound to AAG. Increasing [BUP] with a constant [AAG] + [ANS] returned ANS fluorescence to its unbound status, due to complete displacement of ANS from AAG; bupivacaine’s competitive equilibrium constant, Ki , equals 1-2 μM (pH 7.4, 23oC). Pre-equilibrating AAG with BUP before the rapid (0.008s) addition of excess ANS slowed the binding of ANS to a rate limited by BUP’s dissociation: koff = 12.0 ± 0.5 s-1, corresponding to a half-time ~0.06 seconds. Therefore, although much of the total serum BUP at toxic levels (2-4 µg/mL) will be bound by plasma proteins, dissociation from the tightest binding protein shows that drug is rapidly freed during organ perfusion, allowing newly unbound drug to permeate into the perfused tissues. The very rapid dissociation of BUP from AAG means that equilibrium binding is a very poor index of bio-availability and systemic toxicity of that local anesthetic.
Krishnamurti, C., Mehdi, Z., & Chandrasekhar, V. (2023).
Abstract
Over the past decade, the practice of anesthesiology had become inextricably dependent upon technology. Anesthetics were first discovered, then made increasingly safe, and now, more precise and efficient, all due to tremendous advances in monitoring and delivery technology. Telemedicine has revolutionized medicine and preoperative evaluations and teaching are being done via teleconference and zoom meetings. Patient monitoring has become noninvasive, and closed-loop anesthesia delivery systems are making anesthetic administration very precise and safe. Next-generation technology and innovations will eliminate human errors entirely.
Guevara-López, U., Luna, M. S., & Ramírez, E. H. (2023).
Abstract
Background: The teaching-learning process is a fundamental competence in high-risk environments such as the operating room. Although conventional approaches are based on learning from negative performance, it is convenient to visualize the virtuous behavior of actors in specialties where security events are latent.
Objective: to explore through a survey the perception of crisis in the teaching of anesthesia in Mexico, and to identify the possible causes and precipitating factors.
Methods: A prospective observational design was used, prior approval from the research ethics committee. It was studied by means of a survey with 40 items to people who carry out their professional practice in the Mexican Republic. The positive and/or negative characteristics of specialists, student teachers, the educational program and work environment were explored.
Results: 1,125 participants responded. The highest percentage believed that there is a severe deficit in the teaching of the specialty, indicating in descending order the students, the work environment, and in similar proportions, the structure of the program and the characteristics of the teachers as the causes. Significant statistical differences were found in the attitude and values of the residents, in lack of adherence to educational programs, in the lack of stimuli, motivation and lack of recognition and encouragement to teachers, p < 0.000.
Conclusions: Our findings indicate that anesthesiologists are doing many things “right”, but the existing educational deficit can be corrected to avoid an eventual crisis, suggesting a clinical practice based on evidence and values in a better environment.
Blum, K., Gold, M. S., Cadet, J. L., Lewis, M., McLaughlin, T. J., Braverman, E. R., Elman, I., Carney, B., Cortese, R., Abijo, T., Bagchi, D., Giordano, J., Dennen, C. A., Baron, D., Thanos, P. K., Soni, D., Makale, M., Makale, M., Murphy, K. L., . . . Badgaiyan, R. D. (2023b).
Abstract
Addiction, albeit some disbelievers like Mark Lewis [1], is a chronic, relapsing brain disease, resulting in unwanted loss of control over both substance and non- substance behavioral addictions leading to serious adverse consequences [2]. Addiction scientists and clinicians face an incredible challenge in combatting the current opioid and alcohol use disorder (AUD) pandemic throughout the world. Provisional data from the Centers for Disease Control and Prevention (CDC) shows that from July 2021-2022, over 100,000 individuals living in the United States (US) died from a drug overdose, and 77,237 of those deaths were related to opioid use [3]. This number is expected to rise, and according to the US Surgeon General it is highly conceivable that by 2025 approximately 165,000 Americans will die from an opioid overdose. Alcohol abuse, according to data from the World Health Organization (WHO), results in 3 million deaths worldwide every year, which represents 5.3% of all deaths globally [4].
Kissin, I. (2022).
Abstract
Purpose: The current study assesses how academic medical journals reflected the prescription opioid death crisis. The principal aim was to answer the question: How long did it take to reach definite bibliometric acknowledgment of deaths from opioid epidemic?
Methods: Death-related bibliometric indices were determined for opioids associated with increased mortality. The main of them is the percentage of articles on an individual opioid associated with death among all PubMed articles on that opioid. The bibliometric indices were followed for six 5-year periods, from 1988 to 2017. The time course for each of the indices were compared for two groups of opioids: 1) Those used for the treatment of chronic pain (“root cause of the epidemic”) – such as oxycodone, hydrocodone, and tramadol, and 2) Those which were always associated with the death due to addiction — heroin and methadone. The difference in death-related bibliometric indices between these two groups of opioids was used as an indicator of changes in presentation of opioid deaths.
Results: The articles reporting death associated with oxycodone, tramadol, or hydrocodone became noticeable during 2003-2007, ten years after the beginning of epidemic (1993-1997). It was only in 2013-2017 mortality associated with these opioids were presented at the levels close to those of heroin or methadone. Only during 2013-2017 (twenty years after the beginning of epidemic) was death associated with oxycodone presented in journals as openly (in the article’s titles) as that associated with heroin, or methadone.
Conclusion: The danger of death from treatment of chronic pain with opioids was not properly appreciated for almost twenty years.
Takorov, I., Lukanova, T., Simeonovski, S., Vylcheva, D., Dimitrov, D., Stanimirov, T., Arnaudov, S., & Abrasheva, M. (2022).
Abstract
Spontaneous pneumomediastinum is one of the few rare complications of coronavirus disease – 19 (COVID-19) pneumonia. We report a case of a male patient with COVID-19 disease, severe pneumonia and spontaneous pneumomediastinum, supported via high-flow nasal cannula (HFNC) oxygen supplementation. Factors causing pneumomediastinum are discussed, but further research is still necessary.
Caes, L., Wallace, E., Duncan, C. L., & Dick, B. (2022).
Abstract
Background: Optimal executive functioning is pivotal to successful self-management of chronic pain (e.g., by being able to adapt self-management behaviours to changing situations), thereby contributing to improved health-related quality of life. However, preliminary evidence points to impaired executive functioning in people with chronic pain. Despite adolescence being identified as a sensitive period for the development of appropriate self-management and executive functioning skills, little is known about the associations between chronic pain and executive functioning performance in adolescents. The aim of the study was to pilot a multi-method approach to compare executive functioning, chronic pain, and quality of life between adolescents with and without chronic pain.
Methods: A sample of 22 adolescents with chronic pain (12-18 years, 82% female, mean chronic pain duration = 6.68 years) and 13 pain-free adolescents (age and sex matched) participated. All participants completed a battery of neuropsychological tasks to assess the three key executive functioning components (i.e., inhibition, working memory and cognitive flexibility) and provided self-report on their executive functioning, pain experiences and health-related quality of life.
Results: In addition to confirming the feasibility of the methods, data revealed that 23-62% of adolescents with chronic pain showed problematic performance, using normative scoring, in all three executive functioning components and showed significantly lower performance on all three executive functioning components compared to pain-free adolescents. Self-reported, but not neuropsychologically assessed, working memory and emotional control difficulties were associated with more pain-related interference and lower health-related quality of life.
Conclusion: These preliminary findings reveal the critical need to screen for and address any potential deficits in executive functioning in adolescents with chronic pain to optimise their self-management of pain and subsequent health-related quality of life. The findings also illustrate the feasibility of and need for future systematic, multi-method and prospective investigations in larger samples to further clarify the cyclical associations between chronic pain and executive functioning in adolescents.
Carr, Z. J. (2023).
Abstract
Background: Systemic sclerosis (SSc) is a rare autoimmune disorder with pathological manifestations affecting multiple organ systems. Few studies have examined perioperative outcomes in patients with this disorder. The primary aim of this retrospective single-center comparative cohort analysis was to estimate the incidence of select perioperative complications in a population of SSc patients. In an exploratory analysis, we analyzed the relationship between SSc and susceptibility to select perioperative complications when treated at a large quaternary-care institution.
Methods: We conducted a single-center retrospective, comparative cohort study to compare perioperative outcomes in a SSc (n=258) and a frequency matched control cohort (n=632). We analyzed for the presence of major composite infection (MCI), major adverse cardiac events (MACE), 30-day readmission, 30-day mortality, in-hospital complications, length of stay and airway management outcomes.
Results: MCI was higher in the SSc compared to the control cohort [adjusted odds ratio (ORadj)=5.02 (95%CI: 2.47-10.20) p<0.001]. Surgical site infection (3.5% vs. 0%, p<0.001), and other infection types (5% vs. 0%, p<0.001) were higher in the SSc cohort. MACE was not significantly different between SSc vs. Control groups [6.2% vs. 7.9%, ORadj=1.33 (95%CI: 0.61-2.91) p=0.48]. Higher rates of limited cervical range of motion (13.6% vs. 3.5%, p<0.001), microstomia (11.5% vs. 1.3%, p<0.001) and preoperative difficult airway designation (8.7% vs. 0.5%, p<0.001) were observed in the SSc cohort. Bag mask ventilation grade was similar between groups (p=0.44). After adjustment, there was no between-group difference in Cormack-Lehane grade 3 and 4 view on direct laryngoscopy in SSc patients [ORadj = 1.86 (95%CI: 0.612 -5.66) p=0.18] but evidence of higher rates of video laryngoscopy [ORadj= 1.87 (95%CI:1.07 – 3.27) p=0.03]. Length of stay [median: 0.2 vs. 0.3 days, p=0.08], 30-day mortality [1.2% vs. 0.6%, ORadj=2.79 (95%CI: 0.50-15.6) p=0.24] and readmission [11.5% vs. 8.1%, ORadj=1.64 (95%CI: 0.96 – 2.82) p=0.07] were not statistically significant.
Conclusions: SSc patients demonstrate mostly similar rates of MACE, 30-day mortality, length of stay intraoperative and airway complications. There is evidence of increased risk of overall 30-day MCI risk and readmission after endoscopic procedures.
Bruce, B. K., Weiss, K. E., Ale, C. M., Allman, M., Harrison, T. E., & Fischer, P. R. (2022).
Abstract
Importance: Estimates suggest that 1% of all teens struggle with Postural Orthostatic Tachycardia Syndrome. It can be a devastating condition for the adolescents who do not respond to the currently available pharmacologic and non-pharmacologic interventions. Preliminary data suggests that intensive interdisciplinary treatment may provide an effective intervention that can return these youth to normal functioning including full-time attendance at school, as well as reduce orthostatic symptoms, and psychological distress.
Objective: To determine the effectiveness and durability of a 3-week interdisciplinary treatment in adolescents with Postural Orthostatic Tachycardia Syndrome in improving orthostatic symptoms, functioning, and psychological distress.
Design: Patients diagnosed with Postural Tachycardia Syndrome admitted to an interdisciplinary treatment program were assessed at admission, discharge and 3-month follow-up to determine presence and severity of orthostatic symptoms, as well as functional status including return to school, and depression.
Setting: An intensive interdisciplinary treatment program in a tertiary hospital outpatient setting.
Participants: Forty-five adolescents ages 12-18 with confirmed diagnoses of Postural Tachycardia Syndrome referred to a tertiary medical center for interdisciplinary treatment.
Intervention: A 3-week intensive outpatient interdisciplinary rehabilitation program with significant parental involvement based on a cognitive-behavioral model.
Main Outcome and Measure(s): Self-reported orthostatic symptoms were assessed with the Compass 31; level of functioning was assessed with the Functional Disability Index, depressive symptoms were assessed with the Center for Epidemiological Studies-Depression for Children, and self-reported school attendance was assessed.
Results: Significant improvements were observed and maintained at the end of treatment and at 3-month follow-up on measures of orthostatic symptoms, physical functioning, and psychological distress. At admission, 32% of patients had completed high school or were attending school full-time. At 3-month follow-up, 90% were either attending school full-time or had completed their schooling.
De Witte, P., Bruins, P., Boerma, D., & Kemmel, V. (2023).
Abstract
Background: Surgical cytoreduction and simultaneous hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) is a common treatment for peritoneal carcinomatosis. During intraperitoneal chemotherapy, mitomycin C is frequently used. Mitomycin C is known to be nephrotoxic. Little is known about the effect of systemically absorbed mitomycin C on renal function during HIPEC surgery.
Methods: In twenty-two patients undergoing cytoreductive surgery and HIPEC for peritoneal carcinomatosis the systemic levels of mitomycin C were measured in plasma. The relation of plasma levels of mitomycin C with duration of surgery and complexity of surgery was evaluated.
Furthermore, we evaluated the relation between systemic mitomycin C levels with renal function.
Results Two patients of the total of 22 patients developed acute kidney injury. In these patients, preoperative creatinine level increased from (1) 109 μmol/L to maximum 890 μmol/L on the 6th postoperative day after which renal replacement therapy was started and (2) from 67 μmol/L to 213 μmol/L. Whereas maximum plasma levels of mitomycin C in these 2 patients were 145 μg/L and 280 μg/L compared to the levels in the other patients (167 μg/L ±80.8). Peak levels of plasma creatinine were on post operative day 2. None of the other patients needed renal replacement therapy. Eight patients showed significant increase of plasma creatinine levels, i.e. >20% increase from preoperative values. We did not observe a correlation between complexity of surgery, increased absorption of mitomycin C, higher mitomycin C plasma levels and signs of kidney injury.
Conclusions: Systemic absorption of mitomycin C during HIPEC surgery is independent to extension of cytoreductive surgery and duration of surgery. In this small study group, we observed an impairment of renal function which may be related to systemic absorption of mitomycin C. Further research is warranted to answer possible association of mitomycin C levels in patients at risk for development of AKI.
Mykola, O., Oleksandr, T., Bohdan, K., Volodymyr, L., Serhii, S., Larysa, L., Maksym, K., Maksym, S., Alona, S., Serhii, B., & Oleksandra, S. (2022).
Abstract
Introduction. Pulmonary tuberculosis is a serious problem as in Ukraine as throughout the world. The number of patients with pulmonary tuberculosis is increasing year by year, which is due to the difficulties in early detection of this disease.
The aim. To determine the effectiveness of surgical treatment of patients with pulmonary tuberculosis by using video-assisted thoracoscopic interventions.
Methods. In the Department of Thoracic Surgery of the State University “National Institute of Phthisiology and Pulmonology named after F. G. Yanovsky NAMS of Ukraine” from 2008 to 2022 140 video assisted lung resections were performed in a planned manner for phthisis-surgical patients. The distribution according to the type of resection intervention was as follows: atypical segmental resection – in 30 (21.4 %) cases, typical segmentectomy – in 50 (35.7 %), lobectomy – in 52 (37.2 %), bilobectomy – in 3 (2.1 %), pulmonectomy – in 5 (3.6 %).
The results. The average duration of operative VATS resection interventions was (75.1 ± 22.3) min., intraoperative blood loss was (85.4 ± 1.6) ml, duration of narcotic analgesics prescription in patients with video-assisted thoracoscopic lung resections was (2.20 ± 0.04) days. Early mobilization of patients recorded in 112 (80.0 ± 3.4) cases. The average length of stay of the patient in the intensive care unit after video-assisted thoracoscopic lung resection was (2.6 ± 0.8) days, length of stay of the patient in the hospital in the postoperative period was (12.4 ± 0.5) days. Intraoperative complications were diagnosed in 7 (5.0 ± 1.8) % of patients. The rate of postoperative complications was 22 (15.7 ± 3.1) % of observation. There was no postoperative mortality after minimally invasive surgical interventions. The overall efficiency of performing video-assisted thoracoscopic lung resections was 97.1 %.
Conclusion. The use of video-assisted thoracoscopic is a convenient, effective and low-traumatic method in the treatment of patients with pulmonary tuberculosis. The overall effectiveness of video-assisted thoracoscopic methods for pulmonary tuberculosis was 97.1 %. An adequate assessment of the possibility of performing video-assisted thoracoscopic and the use of methods to prevent complications ensures a predictable course of the intra- and postoperative periods and increases the effectiveness of surgical interventions.
Challenges and Opportunities in Anxiety Disorders
Challenges and Opportunities in Anxiety Disorders
Dr. Caitlin Powell and Dr. Kaitlin Vollet Martin
Abstract
The following study explores the potential impact of COVID-19 on Social Anxiety and Rejection Sensitivity among college students. Over 300 college students completed a survey asking about whether they had contracted COVID-19, and, if they had, additional characteristics (i.e., when they contracted the disease, whether they were symptomatic, whether their symptoms were neurological, how many times they had contracted COVID-19). In addition, they indicated their current levels of Social Anxiety and Rejection Sensitivity, as well as general classroom anxiety. Lastly, participants indicated whether they had been formally diagnosed with related psychological disorders (autism, ADHD, anxiety disorders, mood disorders, rejection sensitivity dysphoria), as well as roughly when they had been diagnosed. Approximately half of the sample reported that they had contracted COVID-19 at least once, and approximately one third of the total sample had been previously diagnosed with anxiety. Results indicated that about one third of those who contracted COVID-19 indicated increases in anxiety or depression post-COVID-19. In addition, females in reported higher Social Anxiety and general classroom anxiety. Results did find that there were higher amounts of Social Anxiety and classroom anxiety among those who had been diagnosed with COVID-19 more recently, these results were no longer significant after controlling for previously diagnosed mental illness. There were otherwise no significant relationships between any aspects of contracting COVID-19 and Social Anxiety, rejection sensitivity, or classroom anxiety. This indicates that while students are reporting increased anxiety and depression, and while recently diagnosed COVID-19 does contribute to Social Anxiety and classroom anxiety, that these increases are likely due to the stress of being ill rather than the virus itself.
Robert D Friedberg, Callie Goodman, Ellison Choate, Hannah Zelcer, Eunice Mendez, Yasaman Movahedi, Sandra Trafalis, Isabella Xie, Megan Neelly, and Joee Zucker
Abstract
The search for transdiagnostic pathways and processes to emotional disorders in youth is an emerging and compelling field. In this mini-review, intolerance of uncertainty is posed as a transdiagnostic pathway. The theoretical foundation of intolerance of uncertainty is discussed. Subtypes of intolerance of uncertainty are explained, a behavioral typology is reviewed, neuropsychological correlates are briefly discussed, and age differences are addressed. The role of the Coronavirus-19 pandemic as a critical incident is examined. Subsequently, the research supporting the association between intolerance of uncertainty and anxiety, obsessive-compulsive,, depression, autism, as well as eating disorders is reviewed. The findings are then integrated into a parsimonious theoretical synthesis. Limitations of the research are delineated and clinical implications are presented
Gilbert Seda, MD, PhD and Sharonya Shrivastava, MD
Abstract
Purpose of Review: Obstructive sleep apnea and chronic insomnia are the most common sleep disorders in adults. Both sleep disorders can adversely affect physical and mental well-being. Cognitive function has been extensively studied in relation to chronic insomnia and obstructive sleep apnea. This paper reviews the recent studies investigating the cognitive effects of insomnia and obstructive sleep apnea as well as the potential benefits of treatment.
Recent Findings: Recent studies indicate that insomnia is associated with impairments in attention, memory, and executive function. Chronic insomnia may have a moderating role in mild cognitive impairment and Alzheimer’s dementia. Mood and anxiety disorders may moderate the effects of insomnia on cognitive function. Hyperarousal and short sleep time associated with insomnia are risk factors for cognitive impairment. Cognitive behavior therapy for insomnia may improve cognitive function but more studies are needed. Nonbenzodiazepine receptor agonists improve insomnia without causing cognitive impairment. Benzodiazepine use is associated with cognitive impairment.
Obstructive sleep apnea is associated with impairments in attention, concentration, memory, and executive function with apnea severity as measured by the apnea hypopnea index and severity of nocturnal hypoxemia being the largest risk factors. Untreated obstructive sleep apnea may have a significant impact on the progression of mild cognitive impairment and Alzheimer’s dementia. The impact of obstructive sleep apnea treatment, particularly with continuous positive airway pressure, appears to mitigate and slow the rate of cognitive decline but more randomized controlled studies are needed.
Summary: Standardized cognitive assessments and larger, long-term controlled prospective studies with diverse populations are needed to further elucidate the cognitive impairments associated with chronic insomnia and obstructive sleep apnea. More studies are needed on the benefits of various treatments for obstructive sleep apnea and insomnia.
Sermin Kesebir and Rüştü Murat Demirer
Abstract
Background: Current classification systems ignore the family histories of patients and psychiatric and medical comorbidity.
Methods: We study a new approach of applying spectral clustering to determine distinct bipolar disorder subtypes, which is data whose clusters are of various sizes and densities. We discovered clusters by processing a SRB (Sinai-Ruelle-Bowen) similarity matrix that reflects the proximity of Von Bertalanffy’s functions fitted to phase growth dynamics of EEG (electroencephalography) within a new pipeline architecture. For this purpose, 109 patients diagnosed with bipolar disorder according to DSM-V (Diagnostic and Statistical Manual of Mental Disorders, fifth edition) were evaluated in remission period cross-sectionally.
Results: We found three distinct bipolar disorder subtypes with the p-values < 0.001. We exhibit mixing sub-shifts of EEG phase gradients such that there are chaotic phase transitions but higher order phase gradients in a cone basin is always strictly convex. More surprisingly, we show that the SRB entropy measures on some time interval although there exist several equilibrium states each corresponds to equilibrium state.
Conclusion: It seems subtypes of the bipolar spectrum were shaped according to seasonality, comorbidity for anxiety disorder and presence of psychotic symptom.
Osman Sinanovic, Muhamed Lepuzanović, Edin Bašagić, Mirsad Muftić, and Sedjad Kahrić
Abstract
Background: Corona infection is primarily a respiratory disease, but the SARS-CoV-2 virus also penetrates other organs, causing various symptoms, including olfactory and gustatory dysfunction, which is why we can consider COVID-19 as a multisystem disease.
Aim: To present review of some aspects of the olfactory and gustatory dysfunction in SARS-CoV- infection.
Methods: The article has an analytical character and review of the literature.
Results and Discussion: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a high similarity with SARS-CoV-1 and uses the same receptors to enter the human body (angiotensin-converting enzyme 2/ACE2). COVID-19 is primarily a disease of the respiratory system, but SARS-CoV-2 also penetrates the other organs including central nervous system (CNS). Patients with SARS-CoV-2 infection can experience a range of clinical manifestations, from no symptoms to critical illness. The entry of the virus into the brain can lead to different neurological and psychiatric manifestations, including loss of smell (anosmia) and the loss of taste (ageusia). The frequency of anosmia and ageusia in patients with COVID-19 varies widely, from 10 to 65%, being the primary symptom in about 12% of patients. For now, the etiopathogenesis of anosmia and ageusia in SARS-CoV-2 infection is still unknown. Most of the analyzed subjects reported olfactory recovery. However, anosmia and ageusia can last several months or even longer. While most patients are expected to recover their sense of smell or taste within the first three months, a major subpopulation of patients might develop long lasting dysfunction. Although a substantial proportion of patients with Covid-19 might develop long lasting of diferent level of ansomia and ageusia it is uncertain what proportion of patients develop persistent dysfunction. Anosmia/ageusia can be as an important risk factor for fog, anxiety, and depression that may show a prolonged and/or delayed impact. However, we do not yet know what long-term effects these disorders may have on the central nervous system and mental health in general.
Conclusion: The COVID-19 is primarily a disease of the respiratory system, but SARS-CoV-2 also penetrates other organs (multisystem disease), causing various symptoms, including olfactory and gustatory dysfunction. The frequency of anosmia and ageusia in patients with COVID-19 is common but according to different papaers varies widely, from 10 to 65%, being the primary symptom in about 12% of patients. Most of the analyzed subjects reported olfactory recovery. However, anosmia and ageusia can last several months or even longer. We do not yet know what long-term consequences these disorders may have on the central nervous system and mental health in general.
Vasiliki S. Raidou, Stilliani Andreadou, Anna Christakou, and Eleni A. Kortianou
Abstract
The coronavirus disease 2019 pandemic increased the need for alternative disease monitoring, medication management, and rehabilitation approaches. During this period, significant adjustments were made to integrate telemedicine into various aspects of healthcare.
This critical review describes the use and effectiveness of digital health approaches adopted for the care of people with chronic respiratory diseases during and beyond the COVID-19 pandemic. A thorough search was conducted in the PubMed database from January 2020 up to December 2022. A total of thirty studies were retrieved and reviewed for the utilization of telehealth services for education, monitoring, assessment, self-management, and rehabilitation in comparison to standard care or not.
During the lockdown patients with chronic obstructive pulmonary disease, asthma, cystic fibrosis, interstitial lung diseases, lung cancer, and neuromuscular disorders indicated positive perception towards remote healthcare delivery. They expressed high levels of satisfaction and achieved self-management in chronic obstructive pulmonary disease and asthma. Remote visits decreased exacerbations of asthma and reinforced smoke cessation in patients with chronic obstructive pulmonary disease. Teleassessment and monitoring increased the percentage of cystic fibrosis and Duchenne Muscular Dystrophy patients seen via telemedicine. Web platforms and mobile applications supported telehealth interventions to reduce stress, depression, and anxiety in patients with cystic fibrosis, assessed the quality of life and physical activity of patients with sarcoidosis, and pursued health education in adolescents with asthma. A few studies carried out telerehabilitation programs in patients with chronic obstructive pulmonary disease, cystic fibrosis, Duchenne Muscular Dystrophy, and sarcoidosis. Findings advocate the feasibility of online exercises, the improvement of exercise capacity, muscle strength, respiratory muscle strength, and the reduction of dyspnea and fatigue.
Rima Dada, Surabhi Gautam, Tanuj Dada, Prabhakar Tiwari, and Manoj Kumar
Abstract
Complex and chronic lifestyle disorders have become the leading cause of death and disability worldwide. They involve multiple morbidities necessitating the attention of numerous healthcare facilities as well as community-based care too. Stress and anxiety brought on by the fast-paced life, unhealthy eating habits, sedentary lifestyle, poor quality of life, polypharmacy, and high medical costs have significantly influenced the development of such multimorbid conditions. Most chronic complex diseases share a similar underlying pathology including high levels of stress, inflammatory immune response, persistent activation of the hypothalamo-pituitary-adrenal axis, oxidative stress, accelerated immune-aging, dysregulated blood flow, enhanced apoptosis and accelerated aging with shorter telomeres and DNA damage. These are modifiable factors which can impact disease progression and no single treatment modality in modern medicine can alone impact all these factors. As a result, the treatment must involve an integrated approach that targets both mind and body and each of these factors which form an architectural framework which supports the onset of these complex lifestyle disease and thus though we may enjoy longer lifespan, but it is accompanied by shorter health span. Yoga, a mind-body intervention with Indian roots, strives to bring about the synchronization of physical and mental health by unraveling and switching on the internal pharmacy and maintenance of homeostasis at cellular and molecular level.
Challenges and Opportunities in Anemia
Challenges and Opportunities in Anemia
Mocket Adolphe Ehouman, Kouakou Eliezer Ngoran, Rufin Kouassi Assare, Ahossan Andre Ehouman, Pamela Nassinata Dosso, and Cyrille K. Konan
Abstract
Background: Anaemia is serious public health problem affecting nearly 42% of children less than 5 years of age globally. In Cote d`Ivoire, 72% of the children aged 6-59 months were anemic in 2019. Anemia is defined as a reduction in the hemoglobin level in the peripheral blood below the normal threshold set for a particular population. Very commonly in the subtropics, helminthes, protozoans or malaria co-infects the same person, causing morbidities that vary according to age and region. This research study aims to characterize the type of anemia observed in 6 years old children infected with helminthes and protozoans in the Western part of Côte d`Ivoire, in order to improve the recommended strategy of care.
Methods: The study was carried out from March 2020 to May 2021 in 22 villages of Biankouma and Man, in Tonkpi Region, with a cohort of 451 children, both male and female, aged from 3 months to 6 years. The children provided venous blood samples for the diagnosis and characterization of anemia (full blood count), urines and stool samples were used for the diagnosis of helminthiasis and protozoosis. Univariate analysis (Chi-2 test (χ2) and P: (Probability) were used for comparison between groups. Significant test was considered at a threshold of 0.05.
Results: Of the 451 children who completed the study, 221 (49.0%) were female and 230 (51.0%) were male. Helminthes infections (230, 51.0%) were more prevalent than the protozoans’ infections (40, 8.9%). 50.0% of children infected by intestinal helminthes (S. mansoni) were anemics (33.9% mild, 64.4% moderate and 1.7% severe). The characterization of anemia revealed that hypochromic microcytic anemia (HMA) was the predominant type, being found in 87 (74.8%) children. It was followed by normochromic microcytic anemia (12 children, 10.4%), normochromic normocytic anemia (09 children, 7.8%), and, finally, hypochromic normocytic anemia (08 children, 7.0%).
Conclusion: S. mansoni infection was highly prevalent among 6 years old children in both sex and in different age groups, although the number of helminthes parasites present during infections was greatest in older children. Similarly, the prevalence of anemia was high, with moderate anemia and HMA being more prevalent in 6 years old children in the western region of Côte d’Ivoire.
Esa Soppi, MD, PhD,
Abstract
Iron deficiency in absence of anemia and blood count changes is a common disorder. Since iron is an essential cofactor not only of hemoglobin and myoglobin but also of numerous enzymes fundamental for many biological processes, it is understandable that the spectrum of iron deficiency related symptoms may be complex, severe and difficult to associate with iron deficiency. This often leads to significant diagnostic delays and a multitude of misleading diagnoses and treatments. Therefore, considering a diagnosis of iron deficiency without anemia requires a high degree of alertness. The second step in the diagnostic process, following consideration of the possibility of iron deficiency, is a careful history that covers all potential causes of deficient iron stores since the patient’s birth and beyond combined by the appropriate investigations. The ferritin concentration is key for ascertaining the diagnosis. A ferritin concentration of less than 30 µg/L in a symptomatic individual means iron deficiency, but the patient may be iron deficient with much higher ferritin concentrations. Simultaneous determination of C-reactive protein with ferritin is practically useless. The treating physician should be familiar with the complexity of ferritin determinations and the interpretation of the results. The mainstay of treatment is oral iron but a considerable proportion of patients are intolerant or insufficiently responsive to oral iron and require intravenous iron therapy. The longer the duration of the iron deficiency, the more complicated the treatment and the patient’s recovery may become. For some patients, iron deficiency seems to be a chronic disorder requiring management exceeding 5 years. In 1–5% of patients, particularly those with a duration of iron deficiency in absence of anemia of more than 15–25 years, the restoration of iron stores does not lead to clinical recovery within 5 years of follow-up. Iron deficiency without anemia has a high impact on the well-being and quality of life of the affected individuals and impacts significantly also on society, since the challenges in recognition, diagnosis and treatment of the condition generate costs probably in excess of 100 million euros/5 million inhabitants.
Dhanya Mohan, Amna Khalifa Alhadari, Dileep Kumar, Sima Abdolla Nejad, Rahaf Mohamad Wardeh, Batool Khan, Madheeha Mahmood, Zuha Fathima, and Mohammed Railey
Abstract
Cryoglobulinemic vasculitis presents with systemic vasculitis including vasculitic rash, fever, peripheral neuropathy, and, in rare cases renal involvement. This could be secondary to infections like hepatitis C, malignancies like myeloma, Non Hodgkin’s lymphoma and chronic lymphocytic leukemia. We encountered a patient who presented with fever, anemia, purpuric skin rash and acute kidney injury due to acute glomerulonephritis with nephritic picture and fluid overload that required hemodialysis.Investigations revealed hemolytic anemia, cryoglobulinemia, proliferative glomerulonephritis with Ig M intra-capillary deposits and hyaline thrombi. Bone marrow biopsy clinched the diagnosis of Chronic lymphocytic B cell lymphoma with CD 20 positivity. Treatment was instituted with Rituximab and Bendamustine. Plasmapheresis was done for hyperviscosity syndrome. With treatment, hemodialysis could be discontinued after 10 weeks and renal functions recovered partially with serum creatinine settling at 1.5 mg/dl. We present this case to highlight the presentation of chronic lymphocytic leukemia with cryoglobulinemic vasculitis that presented with purpura and rapidly progressive renal failure that required dialysis.
Evelim Leal de Freitas Dantas Gomes, Dr., Carolina Cristina Santos Camargo, Debora Nunes Prata Anjos, Etiene Farah Teixeira de Carvalho
Abstract
Onco-hematological diseases are serious conditions and often require aggressive treatment that can lead to systemic complications, consequently affecting musculoskeletal functions as well as physical and functional capacity. Respiratory complications can lead to a greater frequency of hospitalizations and immobility, creating a cycle of sedentarism as well as an increase in morbidity and mortality. The goal of physical therapy in such cases is to restore compromised functions in affected children and adolescents and ensure the performance of activities of daily living and better development.The aim of this review was to bring to light the dysfunctions promoted by onco-hematological diseases of childhood in order to understand the best way to approach the treatment for this population.In this review, the functional alterations of sickle cell anemia, leukemia and bone marrow transplantation were addressed, as well as the interventions used by physiotherapy for the treatment.
Pétur Sigurjónsson, MD Msc., Asta Dogg Jonasdottir, MD Msc., Ingvar H Olafsson, MD, Sigurbergur Karason, MD, PhD, professor, Gudmundur Sigthorsson, MD Msc PhD, and Helga A Sigurjonsdottir, MD, PhD, professor
Abstract
Background and aims of the study: Traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) can cause death and long-term morbidity. Studies indicate that both TBI and SAH may affect pituitary function in both the acute and the chronic phase. The aims of this study were firstly to evaluate the nature of neuroendocrine changes in the acute phase of moderate and severe TBI and all SAH, to evaluate association between neuroendocrine disturbance and indicators of severity of insult as well as hypotension, desaturation and anemia and to evaluated the incidence of neuroendocrine changes after moderate and severe TBI and SAH in the acute phase. Purpose: To explore neuroendocrine disturbances in moderate traumatic brain injury (mTBI), severe TBI (sTBI) and subarachnoid hemorrhage (SAH) in the acute phase.
Methods: The study was a prospective single-center study. Anterior hypothalamic-pituitary (HP) hormone axis were assessed on admission (day 0) with baseline hormone levels and on day 6 post insult with baseline hormone levels and a Synacthen test. From patient charts we recorded for all patients GCS, APACHEII score, length of ICU stay, pupil dilatation, documented hypotension, desaturation and hemoglobin value <80 g/dL. Hunt and Hess grade for SAH group and Injury severity score for TBI group. S100b was measured in all patients on admission. We included 21 TBI patient, 6 moderate TBI and 15 severe TBI, and 19 SAH patients. Anterior hypothalamic-pituitary (HP) hormone axis were assessed on day 0 and 6 post insult in Twenty-one TBI patient and 19 SAH patients.
Results: HP-adrenal axis: The TBI group had significantly lower mean cortisol than the SAH group on day 0, 23.8% of TBI patients had low cortisol and 0% of SAH patients. On day 6, one patient in each group had low cortisol, 6.7% of TBI and 9.1% of SAH. HP-gonadal axis: In males on day 0, 52.9% of TBI patients and 57.1% of SAH patients had suppressed HP-gonadal axis and on day 6, 84.6% of TBI patients and 90% of SAH patients. There was a greater suppression of LH/FSH in the TBI group. HP-thyroid axis: Only one TBI patient (5.9%) had secondary hypothyroidism on day 6. HP-somatotroph axis: On day 0, 52.4% of TBI patients and 35.7% of SAH patients had low IGF-1. On day 6 all but one TBI patient (5.9%) had normalized their IGF-1 but 25% of SAH patients still had low IGF-1. In general, when evaluating association there seemed to more suppression of the hypothalamic-pituitary (HP) gonadal and thyroid axis with more severe insult and adequately more activation of the hypothalamic-pituitary adrenal axis.
Conclusion: Neuroendocrine disturbances in the acute phase of TBI and SAH are common and seem to differ between the two groups. The clinical significance of these disturbances is uncertain.
PRERNA GHODKE, SHARAYU DHANDE, RASHMI HEGDE, AJIT KOSHY, AMISHA SHAH, and PRACHI BALDAWA
Abstract
Background: Plasma cell gingivostomatitis belongs to a group of uncommon benign inflammatory conditions characterised by macular lesions that are bright red, velvety, sharply circumscribed, flat to slightly elevated in nature. Intra-oral lesions can manifest as dense band-like gingival enlargements with plasma-cystic infiltrate seen in the histo-pathological sections. The present case report highlights findings of atypical plasma cell gingivostomatitis further managed through clinical, radiological, histopathology, immunohistochemistry, hematological analysis and treated with surgical periodontal therapy.
Method: Intra-oral periodontal parameters were assessed followed by non-surgical periodontal therapy. In the later phase, internal bevel gingivectomy carried out and approximated with interrupted sutures. Furthermore, gingivoplasty with a 810nm diode laser, for better adaptation of gingival margins was performed. The patient was recalled for follow-up visits at regular intervals and results were maintained.
Result: Intra-oral histopathological sections revealed plasma cell gingivitis whereas hematological reports were suggestive of anemia. Gradual follow up showed reduced gingival inflammation. Post-surgical wound healing was satisfactory. Disappearance of extraoral induration was highlighting feature in the post-operative phase.Further patient was recalled for follow-up visits at regular intervals and results were found to be maintained.
Conclusion: The overall gingival condition was seen to be improving at the follow-up visits. The authors thus conclude that the case of plasma cell gingivitis treated by comprehensive periodontal therapy showed satisfactory results at 3 years follow-up and no recurrence in extra-oral findings was noted.
Challenges and Opportunities in ADHD
Challenges and Opportunities in ADHD
Blandine French, Dr, Anna Price, Dr, Anita Salimi, Abby Russell, Dr
Abstract
In this letter, we summarize key points of learning from research projects on attention deficit hyperactivity disorder (ADHD) that have had patient and public involvement and engagement (PPIE) as a key part of the research process. We share learning from our experiences in delivering research working with PPIE groups with ADHD as top tips for researchers. Our aim is to highlight the importance of including lived experience in ADHD research, share learning, and highlight some of the (potentially invisible) differences in functioning that someone with ADHD can experience in relation to attentional focus, organization, and time management. Specifically, how these might impact the working practices of PPIE groups that include people with ADHD.
Lay summary: This research discusses the importance of involving individuals with ADHD in research and shares insights gained. It emphasizes the unique challenges faced by those with ADHD in terms of attention, organization, and time management, which might not always be apparent. The paper offers practical tips for researchers to better engage with ADHD groups, aiming to ensure that their experiences and perspectives are considered in the research process. In summary, it highlights the value of including firsthand experiences in ADHD research and provides guidance for researchers to enhance this inclusion.
Peter S Jensen, MD, Tiffany D Brandt, PhD, Christopher Kratochvil, MD, Lisa Hunter Romanelli, PhD, James Jaccard, PhD, and Charles Humble, PhD
Abstract
Objective: To understand the benefits of an intensive 6-month practice change intervention (with or without the assistance of an embedded care manager) on primary care providers’ (PCPs’) adoption of evidence-based practices for diagnosing and managing Attention-Deficit/Hyperactivity Disorder (ADHD).
Methods: Following an intensive weekend training in primary care pediatric mental health service delivery, 47 PCPs were randomly assigned to 6 months of ongoing educational support via twice-monthly conference calls, either with or without the additional assistance of a care manager. In addition to the impact of a care manager, basic science-derived predictors of behavior change were examined to explore the impact on PCPs’ initial and subsequent intentions and decisions to adopt 11 specific changes in ADHD practices. The effects of practice obstacles on PCPs’ practice decisions, both initially and over 6 months, were also examined.
Results: PCPs’ initial and subsequent decisions to employ program-targeted ADHD evidence-based practices increased over time and were significantly predicted by underlying hypothesized predictors. Additional support from a care manager had minimal effects on PCPs’ initial and subsequent decisions to apply specific evidence-based ADHD practices. Of note, PCPs’ initial worries and perceptions concerning practice obstacles decreased significantly over time, likely due to twice-monthly support calls.
Conclusions: With intensive and sustained support, PCPs will adopt most evidence-based practices for ADHD diagnosis and treatment. Many initially anticipated obstacles dissipated over time. Additional support of care managers had little impact on PCPs’ longitudinal decisions to adhere to ADHD practice guidelines. Basic science predictors of behavior change are robust correlates of PCPs’ practice changes and should be more routinely applied to understand and improve training outcomes in multiple areas of health service delivery.
Argyro Rentzi
Abstract
In early 2020, the COVID-19 pandemic appeared, due to which strict health measures were announced by the World Health Organization around the world. Among these health measures were strict adherence to hygiene, the use of a protective mask, and social isolation. These measures were immediately implemented in schools worldwide. School, after all, is a living social system that is included in the wider society and interacts with it. For this reason, every important social phenomenon that brings about changes in the way of life of humanity (pandemic, war, etc.) directly affects the school environment, forcing its adaptation to them. Therefore, schools in Greece implemented distance education for all students during the 2020–21 school year, applying inclusive distance education practices for children with special educational needs and disabilities. In Greek schools, children with Attention Deficit Hyperactivity Disorder belong in the category of “students with special educational needs.” Unfortunately, as proven by research, COVID-19 had a negative impact on children diagnosed with Attention Deficit Hyperactivity Disorder, having affected children’s behavior to such an extent that great difficulties are observed in their adapting to the social conditions of school. Because of these results, inclusive pedagogical practices are formed in Greek public primary education to help these children adjust to the school learning environment. This theoretical study will document the above facts and will also present these practices.
Dr. Caitlin Powell and Dr. Kaitlin Vollet Martin
Abstract
The following study explores the potential impact of COVID-19 on Social Anxiety and Rejection Sensitivity among college students. Over 300 college students completed a survey asking about whether they had contracted COVID-19, and, if they had, additional characteristics (i.e., when they contracted the disease, whether they were symptomatic, whether their symptoms were neurological, how many times they had contracted COVID-19). In addition, they indicated their current levels of Social Anxiety and Rejection Sensitivity, as well as general classroom anxiety. Lastly, participants indicated whether they had been formally diagnosed with related psychological disorders (autism, ADHD, anxiety disorders, mood disorders, rejection sensitivity dysphoria), as well as roughly when they had been diagnosed. Approximately half of the sample reported that they had contracted COVID-19 at least once, and approximately one third of the total sample had been previously diagnosed with anxiety. Results indicated that about one third of those who contracted COVID-19 indicated increases in anxiety or depression post-COVID-19. In addition, females in reported higher Social Anxiety and general classroom anxiety. Results did find that there were higher amounts of Social Anxiety and classroom anxiety among those who had been diagnosed with COVID-19 more recently, these results were no longer significant after controlling for previously diagnosed mental illness. There were otherwise no significant relationships between any aspects of contracting COVID-19 and Social Anxiety, rejection sensitivity, or classroom anxiety. This indicates that while students are reporting increased anxiety and depression, and while recently diagnosed COVID-19 does contribute to Social Anxiety and classroom anxiety, that these increases are likely due to the stress of being ill rather than the virus itself.
Alessio Congiu, Roberta Vesentini, Francesca Locatelli, Lorenzo Zamboni, Rosaria Giordano, Silvia Carli, Isabella Barbon, Rebecca Casari, Silvia Melchiori, Simone Campagnari, Tommaso Bovo Francesca Fusina Giuseppe Verlato, and Fabio Lugoboni
Abstract
Background: Several scientific studies indicate that Attention Deficit Hyperactivity Disorder (ADHD) is a risk factor for the development of pathological addiction, including Tobacco Use Disorder (TUD). Despite various hypotheses proposed to explain the reasons for this frequent comorbidity, the limited amount of research aimed at describing the characteristics of this population restricts our understanding of the nature of this relationship. Aims: The purpose of our descriptive and retrospective study is to examine the differences between a group of tobacco users with suspected ADHD and those without it, with respect to socio-demographic characteristics, factors related to tobacco addiction, alcohol consumption, past and current use of illicit substances, and comorbid psychiatric symptoms. Methods: A total of 1166 smokers who were referred to the Addiction Medicine Unit of the University Hospital in Verona between 2015 and 2021 were selected. Users for whom it was not possible to obtain all the necessary information were excluded from the sample. The remaining participants were divided into two groups based on their scores on an ADHD screening test. The group that scored negatively on the screening test (n = 964) was then compared to the group that scored positively on the same test (n = 114). Results: Statistically significant differences emerged between the two groups. Specifically, users in the positive group were found to be more likely to have the marital statuses of “Single” and “Separated/Divorced,” as well as the occupational statuses of “Unemployed,” “Student,” “Teacher,” “Housework,” “Casual Worker,” “Worker,” and “Artisan/Trader.” They also exhibited a higher level of nicotine addiction and reported an increase in smoking in the last 12 months. Furthermore, they had a history of both previous and current use of illicit substances and higher overall levels of anxious and depressive symptoms, regardless of gender. Conclusion: Several factors related to sociodemographic characteristics, smoking behavior, past and current use of illicit substances, and current levels of anxiety and depression could potentially mediate the relationship between ADHD and TUD. Clinicians involved in smoking cessation treatments should take comorbidity with adult ADHD into consideration.
Mohammed Abdulrahman Alrabah, Afnan Abdullah AlMarshedi, and Mansour Abdulaziz E Alharthi
Abstract
Introduction: Lujan-Fryns syndrome (LFS), a rare genetic anomaly first described in 1984, is characterized by a unique constellation of clinical features primarily attributed to mutations in the MED12 gene. These features include intellectual disability, behavioral complexities, and distinct somatic attributes. Although formal psychiatric criteria are lacking, numerous case studies have revealed a co-occurrence of LFS with psychological manifestations, including attention-deficit/hyperactivity disorder (ADHD). This case report explores the intricate relationship between LFS and ADHD, shedding light on potential diagnostic and therapeutic strategies.
Case Presentation: We present the clinical profile of a 13-year-old male diagnosed with LFS, who exhibited hyperactivity and inattention symptoms, leading to a diagnosis of ADHD. The patient’s history included full-term birth, developmental delays, and speech challenges, necessitating special education. Treatment for ADHD included methylphenidate extended-release, behavioral modification techniques, and clonidine, resulting in significant symptom improvement. Marfanoid features were present, and LFS was confirmed through genetic testing. Comprehensive care with a multi-disciplinary approach addressed the associated medical concerns.
Conclusion: Recognizing and addressing the co-occurrence of LFS and ADHD is crucial. This complex interplay presents diagnostic and therapeutic challenges requiring a multidisciplinary approach. The absence of specific medications for LFS-associated ADHD highlights the need for customized treatments. This case report enhances our understanding of their relationship, paving the way for further research to improve clinical care for individuals with both these conditions.
Challenges and Opportunities in Breast Cancer
Challenges and Opportunities in Breast Cancer
Joyce Ayugi, Dr., George Ndagijimana, Dr., Stanley Luyima, Dr., and David Lagoro Kitara
Abstract
Background: Breast Cancer is one of the most common cancers that occur universally among women. The disability-adjusted life years lost by women to breast cancer globally are more than any other cancer. Breast cancer occurs in women worldwide after puberty with increasing rates in later life. Improvements in breast cancer survival began in the 1980s in countries where early detection programs combined with different modes of treatment to eradicate the invasive form of the disease are practiced. Recent data show a higher prevalence of breast cancer among women in Northern Uganda compared to the rest of the country.
This study aimed to determine factors associated with breast cancer awareness, breast self-examination, clinical breast examination, and other modalities for screening and early breast cancer detection among adult women in Gulu Main Market.
Methods: We conducted a cross-sectional study in Gulu’s Main Market in 2020. We recruited Ninety-eight adult women for the study using a random sampling method. The questionnaire had an internal validity of Cronbach’s α=0.72, and a local IRB approved the study. We used SPSS version 26.0 for data analysis, and a p-value less than 0.05 was considered significant.
Results: Most participants were 20-29 years 41(41.8%), married 44(44.9%), monthly incomes of more than one million shillings 51(52.2%), Acholi 81(82.7%), Catholics 46(46.9%), vendors 75(76.5%), work duration in the Market (1-10 years) 64(65.4%), primary level of education 39(39.8%), and had 1-2 pregnancies 37(37.8%). The independent factors associated with breast cancer awareness, breast self-examination, and clinical breast examination were vendor (primary occupation) (β=-0.130, t=-2.979, p=0.004), work duration in the Main Market (1-10 years) (β=-0.186, t=-2.452, p=0.016), and the highest level of education (β=-0.091, t=-2.506, p=0.014).
Conclusions: Breast cancer awareness and downstaging practices among adult women in Gulu’s Main Market are thought-provoking. Women with better socioeconomic status (higher education level, moderate work duration in the Market, and vendors) in Gulu Main Market were more likely aware and practiced breast cancer downstaging activities. There is a need to strengthen publicity on breast cancer-related knowledge for lower-income occupational groups and those with lower educational levels to understand better the importance of conducting early breast cancer detection activities.
Mandeep Singh, Sonal Prakash, Supinder Kaur, Neha Sharma, Deepak Jha, Chandrakant S Pandav, and Frank Hoffman
Abstract
Introduction: Breast cancer is the most common cancer in women around the world, including India. The peak incidence in India is occurring between the ages of 45 -49 years. The solution to problem lies in early detection. The two important methodologies are tactile examination and radiological assessment in form of Mammography. This study explores the concept of enabling and training visually impaired women known as Medical Tactile Examiners with enhanced tactile sense to perform Tactile Breast Examination (TBE) for early detection of Breast Cancer.
Material & Method: A total 1338 women were enrolled. Tactile Breast Examination included intensive and meticulous examination of every cm of breast by three different touch pressures using specialized strips to guide the visually impaired. It was preceded by recording information around lifestyle habits, pregnancy, lactation, menstruation, family history, etc. The radiological assessment included Ultrasound for women less than 40 years and Mammogram for 40 years and above. Data generated was statistically analyzed.
Results: 2.6% of 1338 women were doing routine breast screening; 16% had Body Mass Index > 30; 3% were into substance abuse; 7% experienced menstrual irregularities; 16% were nulliparous; 15% of the parous women had insufficient lactation. 5% had family history of Hereditary Breast and Ovarian Cancer and 4% had previous history of Breast Cancer. Tactile Breast Examination findings were normal in 756/1338 (56.5%), amongst which 8/756 (1%) had radiology reports with BIRADS 4 (suspicious for malignancy) findings. Medical Tactile Examiners during the process of TBE identified palpable breast alterations in 582/1338 (43.5%) of the cases, amongst which 29/582 (5%) were identified as BIRADS 4. The statistical analysis suggests Tactile Breast Examination having a high sensitivity (78.3%) and a very high negative predictive value (98.9%)
Conclusion: The process of Tactile Breast Examination by visually impaired appears apt for breast screening as it detects almost any aberration both benign and malignant in breast which is amenable to human touch and misses out in just 1% changes which can be malignant. It has the potential to become vocational avenue for visually impaired women.
Maseabata Ramathebane Lineo Maja Mopa Sooro, Molungoa Sello, Motselisi Mokhethi, and Kabelo Mputsoe
Abstract
Background: It has been estimated that, more than 60% of the new breast cancer cases and 70% of related deaths will be seen in Low-Middle Income Countries in the coming 20 years. In Lesotho, out of 228 women, 177 had heard about breast cancer while 72.9% had heard of breast cancer screening. Given limited treatment facilities and options in Lesotho, many patients die soon after diagnosis, before they are able to access treatment; to date this cannot be quantified. Another challenge that affects breast cancer management is treatment and travel-related costs, particularly for those not living close to the medical centre. Most patients are coming with advanced disease stage and are sent home for home-based care, some of which could have been prevented with early screening.
Aim: The aim of study is to determine challenges faced by breast cancer patients, the cost to the health system and the opportunities this may bring to the country.
Methods: A quantitative cross-sectional, prospective and retrospective study was conducted on 45 breast cancer patients who were initiated chemotherapy at the only cancer treatment centre in Lesotho; Senkatana oncology clinic located at the Botshabelo complex in Maseru.
Results: The majority of patients were facing challenges of arranging transport to the doctor (83.3%, n=15), of being far from the healthcare facilities even if transportation was available (77.8%, n=14), paying for healthcare (83.3%, n=15), paying for transport (77.8%, n=14) and paying for diagnostic test (88.9%, n=16) in all ages. Majority of patients who presented for care and treatment late faced challenges more than those who presented earlier. Diagnostic and monitoring laboratory test constituted 64.5% of total direct medical costs followed by 24.7 % from chemotherapy.
Conclusion: The challenges faced by breast cancer patients are of financial and practical nature and they get higher for patients who presented at advanced stage for care and treatment. In order to improve breast cancer care and treatment outcome at lower costs efforts for breast cancer awareness need to be intensified so that patients presented early at the health centers. In term of direct medical cost, the largest cost came from the diagnostic and monitoring laboratory tests.
Anita Gadgil, MS, Radhika Srinivasan, MD, PhD, Surita Kantharia, MD, and Partha Basu, MD, PhD
Abstract
Breast cancer tops the list of female cancers both in incidence and mortality. Eastern and south Asian countries have seen a very significant 86%-89% rise in age standardized incidence. Currently 5-year survival of breast cancer in low- and middle-income countries is only 40-60%. There is an urgent need to reduce delays in diagnosis of breast cancer and establish effective referral pathways to improve the observed low survival. Existing literature describes reasons for such delays in breast cancer management extensively, yet does not propose solutions to disrupt this status quo.
Pre-diagnostic delays and diagnostic delays are interdependent due to overlapping socioeconomic and cultural barriers to seeking health, and accessing and accepting care. Non-availability of diagnostic tests or trained human resource and out of pocket expenditure complicate these delays. Present article highlights probable solutions to mitigate these problems with an emphasis on resource limited settings.
Early diagnosis of breast cancer essentially involves reducing the delays in triple assessment of symptomatic patients in the context of limited resources. Clinical breast examination, use of ultrasonography and fine needle aspiration biopsy which are possible to organize at secondary level can mitigate some of the delays. Newer technologies like portable ultrasound devices, use of artificial intelligence, cartridge based real time receptor assay can further reduce the diagnostic delay. Many pilot studies and interventions using newer point of care tests are in progress to establish their role against gold standard investigations in clinical practice.
Delay in diagnosis cannot be mitigated by providing standalone solutions. Robust pathways with provision of green corridor for referrals, task shifting of patient navigation to various grassroot level health care workers, developing contextual practice guidelines, recognising challenges and weaknesses of cancer control system, and realizing importance of equitable distribution of health resources can strengthen the cancer control strategies and mitigate the delays in breast cancer diagnosis.
Robert Charles Burton
Abstract
In Australia and many other high and middle-income countries diagnosis of the most curable stages of breast cancer, early breast cancer (EBC), in women by population based mammographic screening began after 1990. In many of these same and other high and middle-income countries administering adjuvant endocrine and chemotherapy after surgical complete resection of EBC (adjuvant therapy) also began in the 1990s. Some populations then underwent declines in breast cancer mortality that were recorded in population-based Cancer Registries that were attributed to either mammographic screening and/or adjuvant therapy. In only a few populations, for example, in the State of Victoria Australia from 1986-2019 long term trends in the incidence of breast cancer stages at diagnosis have been recorded by the population-based Victorian Cancer registry (VCR). These long-term stage trends have shown that advanced stages of breast cancer have increased or remained stable in those populations, so mammographic screening could not have directly caused the recorded declines in breast cancer mortality in their population-based Cancer Registries. In contrast in Victoria Australia adjuvant therapy use can explain all the recorded mortality decline.
Nitin Telang
Abstract
Background: Progression of early stage breast cancer to advanced stage metastatic disease represents a major cause of death in women. The Luminal A breast cancer subtype exhibits acceptable response to Chemo-endocrine and targeted therapy. However, these treatment options are associated with intrinsic/acquired therapy resistance and emergence chemo-resistant cancer initiating stem cell population, and resultant progression to advanced stage metastatic disease. These limitations emphasize an unmet need for the development of reliable models for cancer stem cells that facilitate identification of efficacious therapeutic alternatives. Documented human consumption, low systemic toxicity, preclinical cancer growth inhibitory efficacy and stem cell targeting efficacy of natural products, such as dietary phytochemicals and nutritional herbs, provide mechanistic leads for these agents as testable therapeutic alternatives.
Objectives: The objectives of the present review are to i.) Provide a systematic discussion of published evidence relevant conceptual background of conventional/targeted therapy and nutritional herbs as testable alternatives, ii.) Growth inhibitory efficacy of nutritional herbs in a cellular model for the Luminal A breast cancer, iii.) Breast cancer stem cell biology and stem cell models for therapy-resistant breast cancer, and iv.) Future research directions.
Conclusions: Collectively, all the elements discussed in the present review validate mechanism-based experimental approaches to identify and prioritize potential therapeutic alternatives.
Future Research: This review provides a rationale for investigations on patient-derived tumor samples that may minimize extrapolation of the preclinical data for their clinical relevance and translatability.
Tommaso Susini, MD, PhD, Irene Renda, Milo Giani, Vania Vezzosi, Gianna Baroni, and Simonetta Bianchi
Abstract
Background: Collagen type XI, alpha 1 (COL11A1) is a minor component of extracellular matrix and its overexpression is associated with tumoral progression and poorer outcome in several human cancers; data on breast cancer are promising but scarce. FGD3 expression has been shown to be a strong independent prognostic factor in breast cancer. The aim of our study was to investigate whether COL11A1 expression correlates with other classic pathologic prognostic factors including FGD3 expression, as well as with clinical outcome, to evaluate its potential use as prognostic factor in breast cancer patients.
Methods: We evaluated by immunohistochemistry COL11A1 expression and we studied the relationship between this protein expression and traditional breast cancer prognostic factors, FGD3 expression, as well as with patients’ outcome.
Results: We found that higher stromal COL11A1 expression was associated with higher tumour grade (G3) (p = 0.001), higher Ki67 proliferation index (p = 0.006), more advanced AJCC stage (p = 0.031) and lower FGD3 expression (p = 0.039). In a case-control analysis, we observed that patients with high-COL11A1 had a higher risk of recurrence (OR = 2.0) and of dying of the disease (OR = 2.0). Patients with high-COL11A1-expressing tumours had shorter disease-free survival and overall survival (difference not significant). There was a linear positive correlation between COL11A1 expression on epithelial tumoral cells and surrounding stromal cells (r = 0.247, p = 0.04).
Conclusion: Our findings suggest that COL11A1 may represent a marker of aggressiveness in invasive breast cancer and that its detection warrants further study on larger series to evaluate its possible use in clinical practice.
Puschel K, Paz S, Fowler M, Vescovic Z, Fuentes I, Sanchez C, and Acevedo F
Abstract
Background: Breast cancer is the leading cause of death from cancer among women in Latin America. Most Latin American countries started national mammogram screening programs a decade ago. The implementation level and effects of screening programs in Latin America have not been evaluated.
Aim: To evaluate the association between screening programs implementation and breast cancer mortality in selected North American and European countries compared to a group of Latin American countries with national screening programs.
Methods: The study applied an ecological design with secondary data from official national and international sources. Join point regression analysis was conducted to describe the trends in mortality rates in a group of five Latin American countries (Brazil, Chile, Colombia, Costa Rica and Mexico) with five Non-Latin American countries (Canada, Spain, Sweden, United Kingdom and the United States of America). The association between screening and mortality rates was explored using correlation and linear regression. National cancer plans were assessed to describe screening strategies among selected countries.
Results: A significant reduction in standardized breast cancer mortality rates was observed in all Non-Latin American countries with an Average Annual Percent Change (AAPC) of -2.00 (p<.05, 95%CI [-3.33, -0.70]) for the period 2010-2020. In contrast, Latin American countries reported a significant increase in the AAPC of +1.38 (p<.05, 95%CI [0.86,1.76]) in breast cancer mortality rates for the period 2010-2020. For Latin American countries, with screening rates below 50%, there was no correlation between screening and mortality rates for the period 1985-2020 (r = -0.17, p = .78). For non-Latin American countries, with screening rates over 70%, the linear regression model explained significantly 55% of the variance in mortality rates (R2aj =.55, F (5,14) = 5.69, p = .005), with a negative and significant effect of mammogram screening on mortality rates (β = -0.14, p = .01). The National Plans analysis revealed an opportunistic screening model for Latin American countries and an organized-systematic model in Non-Latin American countries.
Conclusion: There is an association between the level of implementation of screening programs and mortality rates from breast cancer. Latin American countries should transform their opportunistic strategy into an organized-systematic model.
Donfeng Wu and Seongho Kim
Abstract
Aims: Accurate estimation of the three key parameters (sensitivity, time duration in disease-free state and sojourn time in preclinical state) in cancer screening are critical. Likelihood method with a new link function was applied to the Health Insurance Plan of Greater New York (HIP) breast cancer screening data, to estimate the onset age of preclinical state and the sojourn time in the preclinical state for breast cancer.
Materials and Methods: A new link function to model sensitivity as a function of time in the preclinical state and the sojourn time was adopted. Markov Chain Monte Carlo simulations were used to obtain posterior samples and make inference on the three key parameters. Maximum likelihood estimate was also used for comparison.
Results: The onset age of the preclinical state has a wide range for breast cancer; the peak onset age was 65.07 years (95% credible interval [C.I.], 55.76 to 73.02). The mean sojourn time was 2.00 years (95% C.I., 0.85 to 2.95). The 95 % C.I. for the sojourn time was 0.16 to 5.53 years. Sensitivity at onset of the preclinical state was 0.75 (95% C.I., 0.54 to 0.88); and sensitivity at the end of the preclinical state was 0.84 (95% C.I., 0.67 to 0.88).
Conclusion: The HIP study was the oldest breast cancer mass screening. The estimates reflect key parameters in those days with lower screening sensitivity. However, it is helpful to know other parameters in the planning for future breast cancer screening.
Nayla Robledo, MD, Maria Jose Chico, MD, Maria Paz Swiecicki, MD, Maria Contos, MD, Karina Alejandra Pesce, MD, PhD, and Pamela Causa Andrieu, MD
Abstract
We present and discuss a case report of a 70-year-old patient with a primary carcinoma in accessory breast tissue in the anterior chest wall.
Accessory breast tissue has a reported incidence of 0.3% to 6% in the general population, resulting from an incomplete involution of the mammary milk line. It usually presents as a palpable mass. The most frequent localization of accessory breast tissue and its possible pathologies is the armpit, although it can occur in the inframammary region and rarely on thighs, perineum, groin, or vulva.
The diagnosis is mainly clinical, but imaging findings may be helpful to confirm the suspicion because they are similar to breast cancer within the breast. Ultrasound is the most useful radiological method to evaluate these lesions and guide the suspected diagnosis together with the clinical presentation.
Treatment should be performed under the same principles as breast cancer, both surgical and systemic therapies. The prognosis of accessory breast carcinoma may be poor in cases with delayed diagnosis compared to native breast cancer.
Haim Werner, PhD
Abstract
The insulin-like growth factor-1 hormonal axis has emerged in recent years as a promising therapeutic target in oncology. Empirical support to this view was provided by pre-clinical studies showing that insulin-like growth factor-1 receptor expression and activation constitute fundamental prerequisites for breast cancer development. Unfortunately, the vast majority of phase III clinical trials using monoclonal antibodies against the receptor have been disappointing. As a result of these negative outcomes there is an urgent need to identify predictive biomarkers that may identify potential responders. The present review article is aimed at providing an overview of the role of the insulin-like growth factor-1 axis in breast cancer. Circulating insulin-like growth factor-1 constitutes a risk factor for a number of malignancies, including breast cancer, and various members of the insulin-like growth factor-1 system are produced by the tumoral cells or by stromal cells. In addition, we provide evidence that the mechanism of action of insulin-like growth factor-1 involves interactions with the estrogen receptor as well as with the breast cancer gene-1. Finally, lifestyle factors that are related to insulin-like growth factor-1, such as obesity, have been suggested to have an effect on breast cancer.
Soumya Sonalika, Sushree Sangita Mishra, Subhashree Mahapatro, Devasmita Sahoo
Abstract
Introduction: Breast cancer is a global health concern, accounting for significant morbidity and mortality among women. The fragile ill prepared healthcare systems in low- & middle-income countries need to address these challenges find solutions with their limited resources.
Objectives: Through a critical examination of the literature, this article aims to contribute to a better understanding of breast cancer and to stimulate further research in this field.
Methods & Analysis: This review article provides an in-depth analysis of the current state of breast cancer research, focusing on advancements in diagnosis, treatment, and prevention, as well as the challenges and future directions.
Conclusion: Emerging technologies, such as AI, 3D bioprinting, and nanotechnology, hold promise for addressing the challenges like management of metastatic disease, global disparities in outcomes, and the need for a better understanding of breast cancer etiology and revolutionizing breast cancer care.
Challenges and Opportunities in Nursing
Challenges and Opportunities in Nursing
¹Jacqueline Dunbar-Jacob, PhD, RN ²Elizabeth A. Schlenk, PhD, RN, CNL ³Patricia Tuite, PhD, RN, CCNS
Abstract
Objective: The objective of this narrative review of Doctor of Nursing Practice implementation is to present the background leading to the 2004 American Association of Colleges of Nursing recommendation that the Doctor of Nursing Practice degree be required for advanced practice, discuss the implementation of programs, identify challenges, and provide recommendations for the future.
Method: Both publications and organizational documents, such as white papers and position statements, were reviewed to identify the historical antecedents to the Doctor of Nursing Practice degree recommendation. A review of the status of the degree acceptance by professional organizations was conducted to identify current trends and challenges.
Summary: In 2004, the American Association of Colleges of Nursing voted to require the Doctor of Nursing Practice degree for advanced practice providers by 2015. This occurred within a broad initiative within health science disciplines to move to a practice doctorate. The need for the degree was supported by the Institute of Medicine 2002 recommendation for additional competencies in health professions education and the National Research Council 2005 recommendation that nursing create a clinical doctorate. The goal of the Doctor of Nursing Practice by 2015 has not been met, although programs are growing across the country with varying models of education. Currently nurse anesthesia requires the Doctor of Nursing Practice, clinical nurse specialists have a target date for the requirement of the Doctor of Nursing Practice, nurse practitioner recommendations are to move from the master’s level to the Doctor of Nursing Practice, but certification bodies have not required it, and nurse midwives will accept but have not endorsed a requirement for the Doctor of Nursing Practice. Nurse executives have recommended the Doctor of Nursing Practice for advanced leadership, but many health systems do not require it. There are multiple challenges to developing a pathway to the Doctor of Nursing Practice, including the multiple organizations influencing educational programs, the certification and licensure of graduates, and the employment practices by health systems. These challenges will have to be addressed to achieve the original goal of doctoral education for advanced practice in nursing.
Joyce E. Johnson and Petra Goodman
Abstract
Since 2011, enrollment in Doctor of Nursing Practice (DNP) and Doctor of Philosophy (Ph.D.) graduate nursing programs increased by almost 300%, suggesting that nursing had entered its “golden age.” This steep-growth trajectory reflects the concomitant growth in the number of doctoral programs, today exceeding 435 for the combined DNP and Ph.D. degrees. Unfortunately, the recent progress in advancing nurses in academic programs is hampered by a weakness in a competency crucial for nurses to complete their rigorous academic programs and disseminate research findings or evidence-based practice project interventions: academic writing proficiency. Since nursing curricula at the undergraduate level place lesser emphasis on the humanities, nursing students lack training in the liberal arts compendium of logic, grammar, and rhetoric necessary for effective and articulate communication and dissemination of knowledge in the field of nursing. Data generated from a recent national survey offers new perspectives on the pervasive problem of poor scholarly writing evidenced by students in graduate nursing programs: 97% of graduate papers contain grammatical errors, and only 13% of students demonstrate higher-order skills. While 81% of graduate program faculty ranked their own writing ability as “exceptional” or “highly proficient,” graduate faculty noted that 97% of the time, student papers evidenced numerous grammatical errors, such as flawed sentence structure, run-on sentences, punctuation errors, and ambiguous word choice. These data suggest that graduate nursing programs must pursue avenues to address student writing shortfalls.
The authors opine that the absence of action suggests that graduate nursing programs may be in a dilemma that parallels the metaphor and urban legend of the boiled frog, wherein acceptance of an unacceptable change occurs gradually through minor, unimportant, and unnoticed increments. Aimed at addressing this dilemma, the authors discuss the potential value of offering a customized writing course to refresh and improve students’ basic writing mechanics. A sample curriculum focuses on critical thinking, clarity, and logical flow. Nursing academicians must acknowledge the drift to low writing performance in their students, advance proficiency in scholarly writing to the top of the graduate nursing education’s agenda, and prepare nurses to achieve in nursing’s “golden age.”
Ruth Marchand Tappen, EdD, RN, FAAN, David G. Wolf, Ph.D., MSJ, MSOL, Karen Southard, RN, MHA, CPHQ, Sarah Worch, Ph.D., and Janet Marchand Sopcheck
Abstract
This article presents a quality improvement project involving the first organizational-level test of the effectiveness of a new U.S. Centers for Medicare and Medicaid Services (CMS) endorsed Decision Guide, Go to the Hospital or Stay Here? A Decision Guide for Residents, Families, Friends, and Caregivers. This Decision Guide can enhance resident and family knowledge about nursing home (NH) capabilities and is intended to reduce nursing home resident and family insistence on potentially unnecessary resident transfers and hospital readmissions.
The SQUIRE 2.0 guidelines were the framework for this project. A quality improvement project was conducted in 16 NHs in the southeastern United States to evaluate the effect of the resident and family Decision Guide on hospital readmission rates. Prior to implementation, the investigators provided an online orientation to the project followed by onsite training of nursing home personnel. The NHs then distributed and reviewed the Guide with residents and their family members. NH staff entered data related to readmissions and resident and family responses to the Guide into a secure portion of the project website. NH staff recorded data for three months before Guide implementation and for three months after Guide distribution. Three of the nursing homes lost their upper management team soon after study initiation and were unable to continue. A fourth did not provide complete data. In the 12 remaining facilities, the three-month mean number of readmissions dropped from 27 pre-intervention to 18.58, a 31.2% decrease. Participating facilities reported the Guide was very well received by residents and their families. The facilities’ personnel reported that most residents and family members were unaware of the scope of services provided by the nursing home, an information gap filled by the Decision Guide. They found that implementing this Guide in nursing homes was cost-effective, easy to use, and could substantially reduce readmissions. The results of this quality improvement project demonstrated a significant decrease in hospital readmission rates underscoring its potential for quality improvement in NH care and avoidance of burdensome hospital transfers.
¹Mihail Dimitrios, ²Papatheodorou Maria, and ³Panagiotis Kloutsiniotis
Abstract
Background: Leadership becomes crucial during major crises in which one could expect high levels of burnout and decrease in patient quality of care. The Covid-19 pandemic was a major healthcare crisis where healthcare professional and infrastructure had to cope with unprecedented levels of workload and stressful working conditions. Hence, empirical models for estimating the mitigating role of authentic leadership on nurses’ burnout during the pandemic can contribute to the utilization of best practices in managing effectively the scarce nursing personnel resources.
Aims: To model the influence of leadership, through measures on structural empowerment and work-life balance, on nurses’ burnout and patients’ quality of care, and to measure the nurses΄ perception of their leadership, and the opinion of the leaders regarding their role during the Covid-19 pandemic.
Methods: An institution-based cross-sectional study conducted during the third wave of the pandemic (March-July 2021). After implementing measures to enhance structural empowerment and improve work-life balance, four questionnaires referring to Authentic leadership, Structural empowerment, Work life balance, and Work Burnout were distributed to 650 nursing personnel. Moreover, 200 patients were asked to assess the received quality of care.
Results: 530 valid questionnaires included in the study. Using structural equation modeling, we estimated that authentic leadership significantly influences burnout and preserves patients’ quality of care by enhancing structural empowerment and work-life balance. In assessing attitudes, leadership was rated high, 56±5 SD (max =80) by the nursing personnel. Head nurses rated their leadership significantly higher compared to the nurses, 62,13±10 SD, (p<0,001). Structural empowerment and work-life balance measures were rated 3,55±0.6 SD, and 2,67±0,5 SD, (max =5) respectively. On the burnout subscales, emotional exhaustion and cynicism rated 3,1±0,8 and 2,3±0,7 respectively, and high in professional efficacy, 2±0,5. Patients assessed their quality-of-care 3,8±0.48 SD, (4= very good and 5=excellent).
Conclusion: Our study demonstrates that during major crises, leadership through structural empowerment measures and better work-life conditions mitigates nurses’ burnout and lead them to high levels of professional efficacy, thus preserving patients-quality of care. Moreover, team leaders in healthcare services should be modest and aware of their tendency to overestimate their leadership abilities.
Ekaterini Lambrinou, PhD, Associate Professor, Maria Thodi, RN, Anastasia Samara, MSc, Katerina Philippou, MSc, Lefkios Paikousis, MSc, Panayiota Sentouxi, MSc, Gerasimos Filippatos, MD, FESC, FHFA, FHFSA (h), Vasiliki Bistola, MD, John Parissis, MD, and Martha Kyriakou, PhD
Abstract
Background: Self-care of patients with heart failure (HF) is essential for the effective self-management of their disease, especially during the pandemic era. Self-care assessment instruments give the opportunity to Health Professionals to early recognize possible self-care needs and management of patients with HF.
Aim: The translation and validation of the Greek version of the instrument “Self-Care of Heart Failure Index’’ (Gr-SCHFI), as well as the investigation of the psychometric properties of the instrument in a Greek-speaking population with HF.
Methods: It’s a methodological study of an instrument validation. The psychometric properties of the Greek version of Gr-SCHFI were evaluated through reliability factors (Cronbach’s a and Composite Reliability), reliability of repeat test-retest and validity measures (content validity and concurrent validity). Brislin’s (1970) methodology was used to translate the instrument to Greek language.
Results: The study involved 176 patients, of whom 138 (78%) were men with an average of 69 years old. Most participants were in the NYHA III category [76 (57%)]. Confirmatory factor analysis showed very good measurements in the criteria: RMSEA = 0.07, CFI = 0.97, GFI = 0.98, AGFI = 0.98, NFI = 0.95, TLI = 0.97. The Cronbach’s alpha index and the Composite reliability index had satisfactory internal coherence indicators (Cronbach’s alpha 0.80-0.92, and Composite reliability 0.88-0.96, respectively).
Conclusions: The Gr-SCHFI scale is a reliable and valid self-care assessment instrument for patients with HF. Self-care is necessary in HF where the evaluation and assessment of the self-care of the specific population is very important along the trajectory of the disease.
Yan Jiang, Chaoran Wang, Juan Li, Guangli Mi, Yanan Wang, and Shuling Tian
Abstract
Objective: To explore the clinical effects of quality control circle (QCC) activities on the preparation of instruments, team cooperation and clinical satisfaction of posterior cervical surgery.
Methods: The clinical randomization table was used to select 100 patients who underwent posterior single open-door laminoplasty in the Department of orthopedics of our hospital from January 2020 to January 2021 as the study subjects. In the experimental group, quality control circle activities were used to prepare the surgical instruments before operation, including 32 males and 18 females, with an average age of 58.3 ± 10.5 years; The control group did not use quality control circle activities to prepare the surgical instruments before operation, including 27 males and 22 females, with an average age of 60.5 ± 9.8 years. First, the “quality control circle” activity group was established to carry out quality control circle activity steps such as theme selection, plan formulation, status analysis, goal establishment, problem rectification, specific implementation, effect evaluation and effect evaluation. The database was established by software, and the t-test and chi square test were used for statistical analysis to compare the pre-operative instrument preparation rate of the two groups of patients undergoing cervical posterior single open-door laminoplasty. Finally, the improvement of team consciousness, nursing knowledge, nursing quality, consciousness response and other qualities of all circle members in the experimental group before and after the use of quality control circle activities were analyzed, and the clinical satisfaction of patients and their families, anesthesiologists and chief surgeons with the operation and the integrity rate of equipment preparation were compared between the two groups.
Results: The overall integrity rate of the instruments in the experimental group was 90%, and the overall integrity rate of the instruments in the control group was 74%. The integrity rate of the instruments in the experimental group was significantly higher than that in the control group (P < 0.01). After the implementation of quality control circle activities, the team consciousness, nursing knowledge, nursing quality and consciousness reaction of the circle members in the experimental group were significantly improved compared with those before the implementation of quality control circle activities, and the difference between the two groups was statistically significant (P < 0.01). The overall satisfaction of patients and their families, anesthesiologists, and chief surgeons in the experimental group was 92%, 88%, and 90%, and that of the control group was 76%, 68%, and 74%, respectively. The overall satisfaction of the experimental group was significantly higher than that of the control group (P < 0.05); The integrity rate of surgical instruments preparation in the experimental group was 90%, and that in the control group was 74%. The experimental group was significantly higher than the control group (P < 0.01).
Conclusion: The application of quality control circle activities can improve the integrity of instrument preparation for posterior cervical surgery, improve the satisfaction of patients, family members and medical staff, and improve the quality of surgical care.
Aurelian Udristioiu, Adina Martin, Alexandru Giubelan, Papurica Maria Daniela, Maria Daniela, Liviu Martin, and Delia Nica- Badea
Abstract
The lifespan of a cell in the body oscillates between two fundamental processes, Autophagy, which ensures cell survival, even under conditions of cellular stress, and Apoptosis, which programs the end of cell life, not before the renewal of a new cell in a tissue. Overall, there is a continuation of daily life until a specified date of highlighting the length of the telomeres, in the chromosomal analysis of the cell.
Apoptosis, in the scheduling of cell life, is a normal process which is different from cell necrosis that occurs as a result of physical or chemical aggression. The decision to activate a suicide process is made based on intrinsic or extrinsic apoptotic messages. The intrinsic inducers of apotheosis come from the mitochondria or nucleus. Extrinsic inducers of apotheosis are ligands, cytokines for death receptors, (DR-Death receptors) on each cell surface.
Autophagy: is a homeostatic and catabolic processes that allows the sequestration and lysosomal degradation of cytoplasmic organs and proteins, important for maintaining genomic stability and cell survival. Autophagy is regulated by the Beclin 1 protein, which forms a complex with a class III enzyme, phospho-inoside 3-kinase (PI3K), and serves as a platform for the recruitment of other proteins critical for autophagosome formation.
Conclusions: The most important regulatory mechanism in autoimmunity and oncogenesis process are death receptors, caspases, mitochondria, the Bcl-2 family proto-oncogenes and tumor suppressor gene P53. Pharmacological manipulation of autophagy for cancer prevention and treatment will depend on our ability to successfully recognize the functional status of autophagy in tumors, and the availability of specific autophagic modulators.
Vako Ilda, Eirini Patsaki, Alexandros Kouvarakos, Vaios Grammatis, Ioannis Kouroutzis, Theodora Paisia Apostolidi, Vasiliki Roka, Anastasia Kotanidou, Pavlos Sarafis, and Maria Malliarou
Abstract
Healthcare professionals during the pandemic in the Greek public healthcare system have experienced increased psychological distress, fear and a greater intention to quit their jobs. This study analyzes the factors of moral distress and moral resilience of healthcare professionals employed during the second wave of the pandemic. The target group was the healthcare professionals (HP = 169) who served in the Evaggelismos General Hospital Covid-clinics and -ICU for 2022 and data were collected through life protocols.
Healthcare professionals believe that when faced with moral challenges, they are able to discern them and think clearly. They are especially stressed when they care for more patients than they can safely handle when they are involved in care that causes unnecessary suffering or does not adequately relieve pain or symptoms, and when they notice that patient care is getting worse. Also stressful are the situations, leading to the creation of possible moral distress, when they witness a violation of a standard of practice or moral code. Factors that lead or may lead healthcare professionals to moral distress are nursing safety, unnecessary and deteriorating patient care, and violation of medical confidentiality, violation of standards of practice or moral codes.
The score on the MMD-HP scale indicates low-to-moderate levels of moral distress. Based on the RMRS scale the moral resilience of healthcare professionals is characterized by moderate-to-high with the highest scores per statement seen when patient care is getting worse and feel pressured to ignore situations where patients have not been given adequate information. The healthcare professionals report that they have either left or have considered leaving their position in a clinic due to moral distress, although they are not currently thinking of leaving their position. The factors that increase the frequency of moral distress and decrease their moral resilience are feeling powerless anxiety, nursing/treatment errors, aggressive treatment, caring for more patients than they can handle, substandard patient care, and hierarchical teams.
Soumya Sonalika, Sushree Sangita Mishra, Subhashree Mahapatro, and Devasmita Sahoo
Abstract
Introduction: Breast cancer is a global health concern, accounting for significant morbidity and mortality among women. The fragile ill prepared healthcare systems in low- & middle-income countries need to address these challenges find solutions with their limited resources.
Objectives: Through a critical examination of the literature, this article aims to contribute to a better understanding of breast cancer and to stimulate further research in this field.
Methods & Analysis: This review article provides an in-depth analysis of the current state of breast cancer research, focusing on advancements in diagnosis, treatment, and prevention, as well as the challenges and future directions.
Conclusion: Emerging technologies, such as AI, 3D bioprinting, and nanotechnology, hold promise for addressing the challenges like management of metastatic disease, global disparities in outcomes, and the need for a better understanding of breast cancer etiology and revolutionizing breast cancer care.
Kah Lee and Jennifer Loke
Abstract
Background: Obtaining appointments at a general practice was critical for reducing avoidable hospital admissions, and ultimately saving healthcare costs. In the United Kingdom (UK), problematic access of appointments at individual general practices persisted resulting from increasing health complexities in primary care, which were exacerbated by shortages of medical doctors as general practitioners (GP). The UK government pursued the employing of care-coordinators at primary care networks to allocate care to non-GP health professionals as a solution, but patient demand for GP appointments at individual practices continued to surge.
Aims: This paper reports on an investigation of the ideal way to address patient demand on GP appointments at individual practices. It aimed to report on the effects of two newly implemented joint consultations, one comprising a nursing team and another, a multi-disciplinary team comprising medical doctors and nursing personnel.
Methods: Three reviews were conducted in a 3500 patient-list-sized GP practice located in North-Eastern part of England. The aim was to analyse retrospective data of the telephony system to explore the effect of joint consultations on demand of GP appointments that were made through the telephony system. The number and lengths of incoming telephone calls to secure GP or nursing appointments at the practice were analysed descriptively. The periods of analysis were from January to August in the years 2021, 2022 and 2023.
Results: Since implementation of the two joint consultations, there was a 32% reduction in telephone calls for GP appointments. There was also a shortening of the duration of these telephone calls and decreasing trends of missed calls. The increased lengths of calls towards the tail end of the 3rd review period in 2023 demonstrated increased patient awareness and cooperation for in-depth discussions about their symptoms prior to securing appointments.
Conclusions: The joint consultations had significantly decreased patient demands for GP appointments via telephone. In addition, the joint consultations had not only allowed holistic care needs to be addressed, but also, they had permitted appropriate care to be delivered in a timely fashion. It is therefore important to ensure appropriate healthcare funding to support the implementation of joint consultations at individual GP practices.
Thaisa Mara Leal Cintra Rodrigues, Rita de Cássia de Marchi Barcellos Dal, and Carla Aparecida Arena Ventura
Abstract
Background: The post-pandemic historical moment of COVID-19 has had consequences on the mental health of workers, evidenced by the growing statistics of depression, anxiety, suicidal ideation, panic syndrome, burnout syndrome, psychotic episodes, alcohol and drug addiction, stress, fatigue, and professional exhaustion.
Aims: Analyse the recommendations of the International Labour Organization and the Brazilian laws applicable to occupational mental health to identify documents that address intervening laws in workers’ mental health in the international scientific literature and introduce Bill 3,588/2020, which aims to regulate occupational psychosocial risks.
Methods: Narrative review of the scientific literature in the databases Scopus, Lilacs BVS, PubMed, Cinhal, and Ebesco and document analysis of Brazilian legislation and international recommendations on workers’ mental health and norms related to exposure to occupational psychosocial risks and measures of intervention in mental health.
Results: The International Labour Organization established three Conventions to protect workers’ health. In the Brazilian legal system, six broad and general norms were identified. The narrative prediction resulted in nine intervening laws that address the worker’s mental health. Conclusion: In Brazil, there is no specific legislation regarding the worker’s right to mental health, nor any regulation through Regulatory Norms, which demonstrates the need for the approval of Bill 3,588/2020, pending in the National Congress, which aims at regulating psychosocial risks, such as intervention, management, and prevention measures capable of minimizing mental illness at work.
Regina Jillapalli, Kavita Radhakrishnan, Lorraine Walker, Jane D Champion, and Matthew McGlone
Abstract
Background: Asian Indians, primarily through immigration, are among the three fastest growing Asian minority populations in the United States. Sadly, Asian Indian Women did not meet the Health People 2020’s the 93% cervical cancer screening goal of 93%. Cervical cancer screening rates among Asian Indian Women were 70.5% compared to 82.7% among non-Hispanic Whites. A systematic review revealed the need for qualitative studies to explore influences of cultural beliefs on cervical cancer screening (pap smears) behaviors among Asian Indian Women applying symbolic interactionism theoretical framework.
Purpose: To explore the influence of cultural beliefs on cervical cancer screening behaviors among Asian Indian Women.
Method: A qualitative descriptive ethnographic design used descriptive ethosemantic semi-structured questions to investigate cultural impact on cervical cancer prevention behaviors among a purposive sample of 15 Asian Indian Women between the ages 21 to 49 years of age. Data analysis used inductive analytical methods.
Findings: Five themes influenced cervical cancer screening: locus of control, concept of health, ‘no sex before marriage,’ awareness, and body image. A healthy internal locus of control, sense of being healthy, awareness, and positive body image supported cervical cancer screening behaviors. An external locus of control, belief that health is not a priority, “no sex before marriage,” and low body image were barriers to cervical cancer screening behaviors. Additionally, the concept of “no sex before marriage” influenced timing of the first pap smear. Notwithstanding their cultural beliefs, employment, health insurance, and recommendations from their providers had a positive impact on cervical cancer screening.
Conclusion: Findings from this study have implications for both health policy and clinical practice. Health policy influences funding for basic screening and preventive services. Clinical practice implications encompass fostering partnerships within the community to promote prevention programs and cultural sensitivity training for providers. Future community-based participatory research should address interventional studies to increase compliance for cervical cancer screening and prevention behaviors among Asian Indian Women.
Challenges and Opportunities in Coronary Artery Disease
Challenges and Opportunities in Coronary Artery Disease
Jacques Fair, Esperanza Acuna, and Robert Roberts
Abstract
Coronary artery disease (CAD) is the number one cause of death in the world. It is estimated that 50% of Americans will experience a cardiac event in their lifetime. The underlying pathology leading to coronary artery disease and its clinical manifestations, such as angina, myocardial infarction, and sudden death, is coronary atherosclerosis. While the disease is not usually manifested clinically until the sixth or seventh decade, the underlying pathology is initiated as early as the second or third decade. Numerous randomized clinical trials have shown cardiac morbidity and mortality can be prevented by lowering the risk of known conventional risk factors for CAD, such as decreasing plasma cholesterol or controlling hypertension. Secondary prevention of these conventional risk factors has been very effective; however, primary prevention has been shown to be even more effective. A major barrier to primary prevention is the lack of markers to detect among young, asymptomatic individuals at risk for CAD. The conventional risk factors are often not present until the sixth or seventh decade, which could be late for primary prevention. Genetic predisposition accounts for 50% of the risk for CAD. Recently, over 200 genetic risk variants predisposing to CAD have been discovered. Based on these variants, one can express the genetic risk for CAD in a single number referred to as the Polygenic Risk Score (PRS). The PRS has been evaluated in over one million individuals and shown that those with high genetic risk have the highest incidence of heart disease and can be reduced by 40–50% by utilizing drugs (statins and PCSK9 inhibitors) or lifestyle changes (a favorable diet and increased exercise). The genetic risk for CAD is determined at conception and thus can be predicted anytime from birth onward. The PRS detection of young, asymptomatic individuals based on the PRS enables one to implement early primary prevention. Adoption of the PRS to risk stratify for CAD could represent a paradigm shift in the prevention of this pandemic disease.
Robert Roberts and Esperanza Acuna
Abstract
Coronary artery disease, the number one cause of death in the world, is highly amenable to primary and secondary prevention. Primary prevention is limited because of a lack of biomarkers to detect CAD in its asymptomatic phase. Conventional risk factors, such as hypertension, are not evident until the 6th or 7th decade, which may be late for primary prevention, particularly in males. The recent discovery of genetic risk variants for CAD has the potential, through risk stratification, to detect individuals most appropriate for primary prevention. First, genetic risk accounts for about 50% of predisposition to CAD; second, it is determined at conception and not influenced by age since DNA does not change in one’s lifetime. Thirdly, genetic risk can be determined at any time from birth onward, which is close to ideal for early primary prevention. A review of the literature shows genetic risk can be summarized in a single number, referred to as the polygenic risk score (PRS), and used to stratify risk for CAD. The PRS has been evaluated in over 1 million individuals, and those in the top 20% exhibit a one-to-four-fold greater risk for CAD than those in the bottom 20%. More importantly, clinical studies have shown that decreasing plasma LDL-C or modifying lifestyle decreases the genetic risk for CAD by 50%. The polygenic risk score, obtained from a single blood sample, does not need to be repeated in one’s lifetime. Furthermore, the genetic risk captured by the PRS is relatively independent of conventional risk factors, including family history. The current PRS was determined primarily for individuals of European decent, which can be a limitation to its use in other ethnic groups. However, the results of trials ongoing in several ethnic groups will soon be available. We propose that primary prevention be initiated early in life in individuals in the top 20% of the PRS. The test is relatively inexpensive, and generic drug therapy is also inexpensive. The use of the PRS to risk stratify for CAD would be a paradigm shift for the implementation of early primary prevention of CAD.
Lisa Ferraz, Andreia Fernandes, Ana Faustino, Simão Carvalho, Adriana Pacheco, and Ana Neves
Abstract
Background: Although dobutamine stress echocardiography (DSE) has a high specificity, there is still a subset of patients with false positive tests (FP); whether these results have prognostic value remains unclear.
Aims: To identify the clinical and echocardiographic predictors of FP on DSE and to evaluate the prognostic impact of FP on DSE.
Methods: Retrospective study of 355 consecutive patients who underwent DSE for ischemia assessment over a one-year period: 134 (37,7%) women, 70,3 ± 0,57 years. Demographics, risk factors, clinical and laboratory parameters, and DSE variables were evaluated. Patients were divided into 2 groups regarding the presence (FP+) or absence (FP0) of an FP result on DSE, and a comparative analysis was performed to characterize the groups and identify potential predictors of FP results. Patients were followed for 2 years to assess acute myocardial infarction, hospitalization for acute heart failure (HF), and mortality.
Results: The FP rate was 4.5%. Compared to FP0, patients in group FP+ were younger, baseline wall motion abnormalities were more frequent, they had higher mean blood pressure values at rest and peak stage, and they often had a hypertensive response. There were no significant differences regarding previous coronary artery disease, medication, or a complete left bundle branch block. By multivariate analysis, only mean blood pressure values at rest (OR 0,01; 95%CI 0,005-0,02; p=0,003) and at peak stage (OR 0,02; 95%CI 0,000-0,004; p=0,003) were independent predictors of FP. During follow-up, acute myocardial infarction (FP+: 12.5% vs. FP0: 1.8%, p = 0.046), HF (FP+: 6.3% vs. FP0: 11.5%, p = 0.44), and mortality (FP+: 6.3% vs. FP0: 6.2%, p = 0.65). After adjustment for age, sex, and comorbidities, there were no differences between the groups regarding HF and mortality, but the group FP+ maintained a higher rate of acute myocardial infarction (OR 0,21; 95%CI 0,065-0,354; p = 0,005).
Conclusion: The AFP result on DSE was associated with higher mean blood pressure values during the test and higher rates of acute myocardial infarction during follow-up. Therefore, this result on DSE should be used as a risk marker for ischemic events. It can identify patients who may benefit from aggressive risk factor control and careful clinical follow-up.
Gerald Dorros, M.D., FACC
Abstract
The unintended consequences of the US Centers for Medicare & amp; Medicaid Services’ (CMS) decision not to pay for invasive diagnostic FFR (Fractional Flow Reserve) have precluded its routine diagnostic use in hundreds of thousands of Medicare beneficiaries who suffered inappropriate coronary stent procedures (PCI) that worsened Medicare beneficiaries’ clinical outcomes: 20% of PCI patients have no or uncertain clinical indications but are nevertheless operated upon, and 33% of potential PCI stenoses are non-ischemic and require no PCI. These unnecessary PCIs, often confounded by aging’s anatomical and comorbid complexities, result in preventable complications, repeat procedures, worse clinical outcomes, unwarranted deaths, and an avoidable $1 billion annual expenditure. The best coronary artery disease (CAD) patient care requires astute clinical assessment coupled with diagnostic physiologic ischemic lesion categorization, which directly links lesion treatment to patient management. CMS’ unrealistic expectation that their bundled payment to a single healthcare provider would motivate providers to maximize their profits through efficiently coordinated and improved care was naive; this foolish policy of eschewing invasive FFR payments and expecting providers to absorb the FFR pressure wire’s cost has inflicted potential irreparable harm on all Medicare beneficiaries. CMS has forsaken its mission to attain the “highest level of health for all people, where everyone has a fair and just opportunity to attain their optimal health regardless of race, ethnicity, disability, sexual orientation, gender identity, socioeconomic status, geography, preferred language, or other factors that affect access to care and health outcomes”.
George Trad, MD, Rasiq Zackria, DO, Syed Abdul Basit, MD, and John K. Ryan, MD
Abstract
Necrotizing pancreatitis (NP) is a life-threatening complication of acute pancreatitis. It requires an extended hospital stay, aggressive management, and a higher risk of mortality. Risk factors such as comorbidities in the patient’s history, including a history of coronary artery disease and cerebrovascular disease, can increase the risk of developing necrotizing pancreatitis. The presentation of necrotizing pancreatitis is similar to acute pancreatitis, but specific labs such as hematocrit levels can be monitored to anticipate the development of necrotizing pancreatitis. In addition, diagnostic imaging must be obtained to classify necrotizing pancreatitis and aid in management choice. Fluid hydration, adequate pain management, and nutritional support are the principles of treating necrotizing pancreatitis. Deciding whether to drain the necrotic collection or not is usually determined based on the type of necrosis present and whether it is infected. Infected necrotizing pancreatitis can also occur, and patients usually need to be monitored closely with appropriate antibiotics for a long duration. Patients affected by necrotizing pancreatitis can potentially develop complications that can lead to devastating outcomes. Necrotizing pancreatitis complications can occur due to an inflammatory reaction on the adjacent structure, such as splanchnic vein thrombosis, gastrointestinal fistula, or an inflammatory reaction within the pancreas leading to an exocrine and an endocrine pancreatic insufficiency. We present here a literature review of necrotizing pancreatitis and the complications that can arise from it.
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