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


    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


    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


    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


    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


    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.


    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


    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


    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


    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.


    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


    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.


    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


    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


    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


    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


    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 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


    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


    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.


    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


    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


    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


    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 virusHow 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


    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


    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


    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


    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:

      1. during the differential diagnosis of a suspected new autoimmune condition,
      1. in case of poor response or flare of symptoms on initiating immunosuppressive therapy,
    1. during systematic screening prior to starting immunosuppressive medication, along with blood born viruses and tuberculosis.

    Amorn Sankhaanuruk, M.D.

    Nuntana Kasitanon, M.D.

    Worawit Louthrenoo, M.D.


    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


    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.


    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


    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;


    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.


    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


    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


    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


    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


    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


    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)


    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.


    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.

    Shamir O Cawich, Greg Padmore, Sahle Griffith, Karisha Hinkson-LaCorbiniere & Reena Patel


    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 FairEsperanza AcunaRobert Roberts


    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


    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)


    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


    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


    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.

    Yahia M Lodi, MD, FAHA, FANA, FAAN & Aria Soltani


    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.


    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


    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

    Shamir O Cawich, Greg Padmore, Sahle Griffith, Karisha Hinkson-LaCorbiniere & Reena Patel


    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


    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


    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.


    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


    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


    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


    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.

    James Repace


    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


    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


    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


    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.

    Parvin Mehdipour


    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 STsequences, 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 levelThe 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)


    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)


    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)


    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)


    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)


    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,


    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)


    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)


    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)


    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)


    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)


    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)


    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)


    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)


    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)


    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)


    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)


    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)


    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)


    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)


    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)



    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.


    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.


    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%.


    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)


    AimsThe 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)


    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


    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


    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


    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.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


    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


    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


    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


    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


    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


    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


    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). 


    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). 


    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).


    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.

    vinar dapibus leo.

    Nagasaka, Y., & Tsuchiya, M. (2021). 


    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). 


    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


    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


    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


    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


    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.

    Spencer Lofink, BS and Thomas Trumble, MD


    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


    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.


    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). 


    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.

    De Mendonça, M. C. (2023).


    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).


    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). 


    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). 


    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). 


    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). 


    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). 


    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). 


    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). 


    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). 


    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). 


    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). 


    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


    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


    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


    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


    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


    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


    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


    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


    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,


    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


    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


    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


    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.



    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


    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


    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


    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


    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


    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


    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


    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


    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


    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


    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


    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)