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    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) also began in the 1990s. Some populations then underwent declines in breast cancer mortality that were recorded in population-based Cancer Registries that were attributed to either mammographic screening and/or adjuvant therapy. In only a few populations, for example, in the State of Victoria Australia from 1986-2019 long term trends in the incidence of breast cancer stages at diagnosis have been recorded by the population-based Victorian Cancer registry (VCR). These long-term stage trends have shown that advanced stages of breast cancer have increased or remained stable in those populations, so mammographic screening could not have directly caused the recorded declines in breast cancer mortality in their population-based Cancer Registries. In contrast in Victoria Australia adjuvant therapy use can explain all the recorded mortality decline.

    Nitin Telang


    Background: Progression of early stage breast cancer to advanced stage metastatic disease represents a major cause of death in women. The Luminal A breast cancer subtype exhibits acceptable response to Chemo-endocrine and targeted therapy. However, these treatment options are associated with intrinsic/acquired therapy resistance and emergence chemo-resistant cancer initiating stem cell population, and resultant progression to advanced stage metastatic disease. These limitations emphasize an unmet need for the development of reliable models for cancer stem cells that facilitate identification of efficacious therapeutic alternatives. Documented human consumption, low systemic toxicity, preclinical cancer growth inhibitory efficacy and stem cell targeting efficacy of natural products, such as dietary phytochemicals and nutritional herbs, provide mechanistic leads for these agents as testable therapeutic alternatives. 

    Objectives: The objectives of the present review are to i.) Provide a systematic discussion of published evidence relevant conceptual background of conventional/targeted therapy and nutritional herbs as testable alternatives, ii.) Growth inhibitory efficacy of nutritional herbs in a cellular model for the Luminal A breast cancer, iii.) Breast cancer stem cell biology and stem cell models for therapy-resistant breast cancer, and iv.) Future research directions.

    Conclusions: Collectively, all the elements discussed in the present review validate mechanism-based experimental approaches to identify and prioritize potential therapeutic alternatives.

    Future Research: This review provides a rationale for investigations on patient-derived tumor samples that may minimize extrapolation of the preclinical data for their clinical relevance and translatability.

    Tommaso Susini, MD, PhD, Irene Renda, Milo Giani, Vania Vezzosi, Gianna Baroni, and Simonetta Bianchi


    Background: Collagen type XI, alpha 1 (COL11A1) is a minor component of extracellular matrix and its overexpression is associated with tumoral progression and poorer outcome in several human cancers; data on breast cancer are promising but scarce. FGD3 expression has been shown to be a strong independent prognostic factor in breast cancer. The aim of our study was to investigate whether COL11A1 expression correlates with other classic pathologic prognostic factors including FGD3 expression, as well as with clinical outcome, to evaluate its potential use as prognostic factor in breast cancer patients.

    Methods: We evaluated by immunohistochemistry COL11A1 expression and we studied the relationship between this protein expression and traditional breast cancer prognostic factors, FGD3 expression, as well as with patients’ outcome.

    Results: We found that higher stromal COL11A1 expression was associated with higher tumour grade (G3) (p = 0.001), higher Ki67 proliferation index (p = 0.006), more advanced AJCC stage (p = 0.031) and lower FGD3 expression (p = 0.039). In a case-control analysis, we observed that patients with high-COL11A1 had a higher risk of recurrence (OR = 2.0) and of dying of the disease (OR = 2.0). Patients with high-COL11A1-expressing tumours had shorter disease-free survival and overall survival (difference not significant). There was a linear positive correlation between COL11A1 expression on epithelial tumoral cells and surrounding stromal cells (r = 0.247, p = 0.04).

    Conclusion: Our findings suggest that COL11A1 may represent a marker of aggressiveness in invasive breast cancer and that its detection warrants further study on larger series to evaluate its possible use in clinical practice.

    Puschel K, Paz S, Fowler M, Vescovic Z, Fuentes I, Sanchez C, and Acevedo F


    Background: Breast cancer is the leading cause of death from cancer among women in Latin America. Most Latin American countries started national mammogram screening programs a decade ago. The implementation level and effects of screening programs in Latin America have not been evaluated.

    Aim: To evaluate the association between screening programs implementation and breast cancer mortality in selected North American and European countries compared to a group of Latin American countries with national screening programs.

    MethodsThe study applied an ecological design with secondary data from official national and international sources. Join point regression analysis was conducted to describe the trends in mortality rates in a group of five Latin American countries (Brazil, Chile, Colombia, Costa Rica and Mexico) with five Non-Latin American countries (Canada, Spain, Sweden, United Kingdom and the United States of America). The association between screening and mortality rates was explored using correlation and linear regression. National cancer plans were assessed to describe screening strategies among selected countries.

    ResultsA significant reduction in standardized breast cancer mortality rates was observed in all Non-Latin American countries with an Average Annual Percent Change (AAPC) of -2.00 (p<.05, 95%CI [-3.33, -0.70]) for the period 2010-2020. In contrast, Latin American countries reported a significant increase in the AAPC of +1.38 (p<.05, 95%CI [0.86,1.76]) in breast cancer mortality rates for the period 2010-2020. For Latin American countries, with screening rates below 50%, there was no correlation between screening and mortality rates for the period 1985-2020 (r = -0.17, p = .78). For non-Latin American countries, with screening rates over 70%, the linear regression model explained significantly 55% of the variance in mortality rates (R2aj =.55, F (5,14) = 5.69, p = .005), with a negative and significant effect of mammogram screening on mortality rates (β = -0.14, p = .01). The National Plans analysis revealed an opportunistic screening model for Latin American countries and an organized-systematic model in Non-Latin American countries.

    ConclusionThere is an association between the level of implementation of screening programs and mortality rates from breast cancer. Latin American countries should transform their opportunistic strategy into an organized-systematic model.

    Donfeng Wu and Seongho Kim


    Aims: Accurate estimation of the three key parameters (sensitivity, time duration in disease-free state and sojourn time in preclinical state) in cancer screening are critical. Likelihood method with a new link function was applied to the Health Insurance Plan of Greater New York (HIP) breast cancer screening data, to estimate the onset age of preclinical state and the sojourn time in the preclinical state for breast cancer.

    Materials and Methods: A new link function to model sensitivity as a function of time in the preclinical state and the sojourn time was adopted. Markov Chain Monte Carlo simulations were used to obtain posterior samples and make inference on the three key parameters. Maximum likelihood estimate was also used for comparison.

    Results: The onset age of the preclinical state has a wide range for breast cancer; the peak onset age was 65.07 years (95% credible interval [C.I.], 55.76 to 73.02). The mean sojourn time was 2.00 years (95% C.I., 0.85 to 2.95). The 95 % C.I. for the sojourn time was 0.16 to 5.53 years. Sensitivity at onset of the preclinical state was 0.75 (95% C.I., 0.54 to 0.88); and sensitivity at the end of the preclinical state was 0.84 (95% C.I., 0.67 to 0.88).   

    Conclusion: The HIP study was the oldest breast cancer mass screening. The estimates reflect key parameters in those days with lower screening sensitivity. However, it is helpful to know other parameters in the planning for future breast cancer screening.

    Nayla Robledo, MD, Maria Jose Chico, MD, Maria Paz Swiecicki, MD, Maria Contos, MD, Karina Alejandra Pesce, MD, PhD, and Pamela Causa Andrieu, MD


    We present and discuss a case report of a 70-year-old patient with a primary carcinoma in accessory breast tissue in the anterior chest wall.

     Accessory breast tissue has a reported incidence of 0.3% to 6% in the general population, resulting from an incomplete involution of the mammary milk line. It usually presents as a palpable mass. The most frequent localization of accessory breast tissue and its possible pathologies is the armpit, although it can occur in the inframammary region and rarely on thighs, perineum, groin, or vulva.

     The diagnosis is mainly clinical, but imaging findings may be helpful to confirm the suspicion because they are similar to breast cancer within the breast. Ultrasound is the most useful radiological method to evaluate these lesions and guide the suspected diagnosis together with the clinical presentation.

    Treatment should be performed under the same principles as breast cancer, both surgical and systemic therapies. The prognosis of accessory breast carcinoma may be poor in cases with delayed diagnosis compared to native breast cancer.

    Haim Werner, PhD


    The insulin-like growth factor-1 hormonal axis has emerged in recent years as a promising therapeutic target in oncology. Empirical support to this view was provided by pre-clinical studies showing that insulin-like growth factor-1 receptor expression and activation constitute fundamental prerequisites for breast cancer development. Unfortunately, the vast majority of phase III clinical trials using monoclonal antibodies against the receptor have been disappointing. As a result of these negative outcomes there is an urgent need to identify predictive biomarkers that may identify potential responders. The present review article is aimed at providing an overview of the role of the insulin-like growth factor-1 axis in breast cancer. Circulating insulin-like growth factor-1 constitutes a risk factor for a number of malignancies, including breast cancer, and various members of the insulin-like growth factor-1 system are produced by the tumoral cells or by stromal cells. In addition, we provide evidence that the mechanism of action of insulin-like growth factor-1 involves interactions with the estrogen receptor as well as with the breast cancer gene-1. Finally, lifestyle factors that are related to insulin-like growth factor-1, such as obesity, have been suggested to have an effect on breast cancer.

    Soumya Sonalika, Sushree Sangita Mishra, Subhashree Mahapatro, Devasmita Sahoo


    Introduction: Breast cancer is a global health concern, accounting for significant morbidity and mortality among women. The fragile ill prepared healthcare systems in low- & middle-income countries need to address these challenges find solutions with their limited resources.

    Objectives: Through a critical examination of the literature, this article aims to contribute to a better understanding of breast cancer and to stimulate further research in this field.

    Methods & Analysis: This review article provides an in-depth analysis of the current state of breast cancer research, focusing on advancements in diagnosis, treatment, and prevention, as well as the challenges and future directions.

    Conclusion: Emerging technologies, such as AI, 3D bioprinting, and nanotechnology, hold promise for addressing the challenges like management of metastatic disease, global disparities in outcomes, and the need for a better understanding of breast cancer etiology and revolutionizing breast cancer care.

    Challenges and Opportunities in Nursing

    Challenges and Opportunities in Nursing

    ¹Jacqueline Dunbar-Jacob, PhD, RN ²Elizabeth A. Schlenk, PhD, RN, CNL ³Patricia Tuite, PhD, RN, CCNS


    Objective: The objective of this narrative review of Doctor of Nursing Practice implementation is to present the background leading to the 2004 American Association of Colleges of Nursing recommendation that the Doctor of Nursing Practice degree be required for advanced practice, discuss the implementation of programs, identify challenges, and provide recommendations for the future.

    Method: Both publications and organizational documents, such as white papers and position statements, were reviewed to identify the historical antecedents to the Doctor of Nursing Practice degree recommendation. A review of the status of the degree acceptance by professional organizations was conducted to identify current trends and challenges.

    Summary: In 2004, the American Association of Colleges of Nursing voted to require the Doctor of Nursing Practice degree for advanced practice providers by 2015. This occurred within a broad initiative within health science disciplines to move to a practice doctorate. The need for the degree was supported by the Institute of Medicine 2002 recommendation for additional competencies in health professions education and the National Research Council 2005 recommendation that nursing create a clinical doctorate. The goal of the Doctor of Nursing Practice by 2015 has not been met, although programs are growing across the country with varying models of education. Currently nurse anesthesia requires the Doctor of Nursing Practice, clinical nurse specialists have a target date for the requirement of the Doctor of Nursing Practice, nurse practitioner recommendations are to move from the master’s level to the Doctor of Nursing Practice, but certification bodies have not required it, and nurse midwives will accept but have not endorsed a requirement for the Doctor of Nursing Practice. Nurse executives have recommended the Doctor of Nursing Practice for advanced leadership, but many health systems do not require it. There are multiple challenges to developing a pathway to the Doctor of Nursing Practice, including the multiple organizations influencing educational programs, the certification and licensure of graduates, and the employment practices by health systems. These challenges will have to be addressed to achieve the original goal of doctoral education for advanced practice in nursing.

    Joyce E. Johnson and Petra Goodman


    Since 2011, enrollment in Doctor of Nursing Practice (DNP) and Doctor of Philosophy (Ph.D.) graduate nursing programs increased by almost 300%, suggesting that nursing had entered its “golden age.” This steep-growth trajectory reflects the concomitant growth in the number of doctoral programs, today exceeding 435 for the combined DNP and Ph.D. degrees. Unfortunately, the recent progress in advancing nurses in academic programs is hampered by a weakness in a competency crucial for nurses to complete their rigorous academic programs and disseminate research findings or evidence-based practice project interventions: academic writing proficiency. Since nursing curricula at the undergraduate level place lesser emphasis on the humanities, nursing students lack training in the liberal arts compendium of logic, grammar, and rhetoric necessary for effective and articulate communication and dissemination of knowledge in the field of nursing. Data generated from a recent national survey offers new perspectives on the pervasive problem of poor scholarly writing evidenced by students in graduate nursing programs: 97% of graduate papers contain grammatical errors, and only 13% of students demonstrate higher-order skills. While 81% of graduate program faculty ranked their own writing ability as “exceptional” or “highly proficient,” graduate faculty noted that 97% of the time, student papers evidenced numerous grammatical errors, such as flawed sentence structure, run-on sentences, punctuation errors, and ambiguous word choice. These data suggest that graduate nursing programs must pursue avenues to address student writing shortfalls.

    The authors opine that the absence of action suggests that graduate nursing programs may be in a dilemma that parallels the metaphor and urban legend of the boiled frog, wherein acceptance of an unacceptable change occurs gradually through minor, unimportant, and unnoticed increments. Aimed at addressing this dilemma, the authors discuss the potential value of offering a customized writing course to refresh and improve students’ basic writing mechanics. A sample curriculum focuses on critical thinking, clarity, and logical flow. Nursing academicians must acknowledge the drift to low writing performance in their students, advance proficiency in scholarly writing to the top of the graduate nursing education’s agenda, and prepare nurses to achieve in nursing’s “golden age.”

    Ruth Marchand Tappen, EdD, RN, FAAN, David G. Wolf, Ph.D., MSJ, MSOL, Karen Southard, RN, MHA, CPHQ, Sarah Worch, Ph.D., and Janet Marchand Sopcheck


    This article presents a quality improvement project involving the first organizational-level test of the effectiveness of a new U.S. Centers for Medicare and Medicaid Services (CMS) endorsed Decision Guide, Go to the Hospital or Stay Here? A Decision Guide for Residents, Families, Friends, and Caregivers. This Decision Guide can enhance resident and family knowledge about nursing home (NH) capabilities and is intended to reduce nursing home resident and family insistence on potentially unnecessary resident transfers and hospital readmissions.

    The SQUIRE 2.0 guidelines were the framework for this project. A quality improvement project was conducted in 16 NHs in the southeastern United States to evaluate the effect of the resident and family Decision Guide on hospital readmission rates. Prior to implementation, the investigators provided an online orientation to the project followed by onsite training of nursing home personnel. The NHs then distributed and reviewed the Guide with residents and their family members. NH staff entered data related to readmissions and resident and family responses to the Guide into a secure portion of the project website. NH staff recorded data for three months before Guide implementation and for three months after Guide distribution. Three of the nursing homes lost their upper management team soon after study initiation and were unable to continue. A fourth did not provide complete data. In the 12 remaining facilities, the three-month mean number of readmissions dropped from 27 pre-intervention to 18.58, a 31.2% decrease. Participating facilities reported the Guide was very well received by residents and their families. The facilities’ personnel reported that most residents and family members were unaware of the scope of services provided by the nursing home, an information gap filled by the Decision Guide. They found that implementing this Guide in nursing homes was cost-effective, easy to use, and could substantially reduce readmissions. The results of this quality improvement project demonstrated a significant decrease in hospital readmission rates underscoring its potential for quality improvement in NH care and avoidance of burdensome hospital transfers.

    ¹Mihail Dimitrios, ²Papatheodorou Maria, and ³Panagiotis Kloutsiniotis


    Background: Leadership becomes crucial during major crises in which one could expect high levels of burnout and decrease in patient quality of care. The Covid-19 pandemic was a major healthcare crisis where healthcare professional and infrastructure had to cope with unprecedented levels of workload and stressful working conditions. Hence, empirical models for estimating the mitigating role of authentic leadership on nurses’ burnout during the pandemic can contribute to the utilization of best practices in managing effectively the scarce nursing personnel resources.

    Aims: To model the influence of leadership, through measures on structural empowerment and work-life balance, on nurses’ burnout and patients’ quality of care, and to measure the nurses΄ perception of their leadership, and the opinion of the leaders regarding their role during the Covid-19 pandemic.

    Methods: An institution-based cross-sectional study conducted during the third wave of the pandemic (March-July 2021). After implementing measures to enhance structural empowerment and improve work-life balance, four questionnaires referring to Authentic leadership, Structural empowerment, Work life balance, and Work Burnout were distributed to 650 nursing personnel. Moreover, 200 patients were asked to assess the received quality of care.

    Results: 530 valid questionnaires included in the study. Using structural equation modeling, we estimated that authentic leadership significantly influences burnout and preserves patients’ quality of care by enhancing structural empowerment and work-life balance. In assessing attitudes, leadership was rated high, 56±5 SD (max =80) by the nursing personnel. Head nurses rated their leadership significantly higher compared to the nurses, 62,13±10 SD, (p<0,001). Structural empowerment and work-life balance measures were rated 3,55±0.6 SD, and 2,67±0,5 SD, (max =5) respectively. On the burnout subscales, emotional exhaustion and cynicism rated 3,1±0,8 and 2,3±0,7 respectively, and high in professional efficacy, 2±0,5. Patients assessed their quality-of-care 3,8±0.48 SD, (4= very good and 5=excellent).

    Conclusion: Our study demonstrates that during major crises, leadership through structural empowerment measures and better work-life conditions mitigates nurses’ burnout and lead them to high levels of professional efficacy, thus preserving patients-quality of care. Moreover, team leaders in healthcare services should be modest and aware of their tendency to overestimate their leadership abilities.

    Ekaterini Lambrinou, PhD, Associate Professor, Maria Thodi, RN, Anastasia Samara, MSc, Katerina Philippou, MSc, Lefkios Paikousis, MSc, Panayiota Sentouxi, MSc, Gerasimos Filippatos, MD, FESC, FHFA, FHFSA (h), Vasiliki Bistola, MD, John Parissis, MD, and Martha Kyriakou, PhD


    Background: Self-care of patients with heart failure (HF) is essential for the effective self-management of their disease, especially during the pandemic era. Self-care assessment instruments give the opportunity to Health Professionals to early recognize possible self-care needs and management of patients with HF.

    Aim: The translation and validation of the Greek version of the instrument “Self-Care of Heart Failure Index’’ (Gr-SCHFI), as well as the investigation of the psychometric properties of the instrument in a Greek-speaking population with HF.

    Methods: It’s a methodological study of an instrument validation. The psychometric properties of the Greek version of Gr-SCHFI were evaluated through reliability factors (Cronbach’s a and Composite Reliability), reliability of repeat test-retest and validity measures (content validity and concurrent validity). Brislin’s (1970) methodology was used to translate the instrument to Greek language.

    Results: The study involved 176 patients, of whom 138 (78%) were men with an average of 69 years old. Most participants were in the NYHA III category [76 (57%)]. Confirmatory factor analysis showed very good measurements in the criteria: RMSEA = 0.07, CFI = 0.97, GFI = 0.98, AGFI = 0.98, NFI = 0.95, TLI = 0.97. The Cronbach’s alpha index and the Composite reliability index had satisfactory internal coherence indicators (Cronbach’s alpha 0.80-0.92, and Composite reliability 0.88-0.96, respectively).

    Conclusions: The Gr-SCHFI scale is a reliable and valid self-care assessment instrument for patients with HF. Self-care is necessary in HF where the evaluation and assessment of the self-care of the specific population is very important along the trajectory of the disease.

    Yan Jiang, Chaoran Wang, Juan Li, Guangli Mi, Yanan Wang, and Shuling Tian


    Objective: To explore the clinical effects of quality control circle (QCC) activities on the preparation of instruments, team cooperation and clinical satisfaction of posterior cervical surgery.

    Methods: The clinical randomization table was used to select 100 patients who underwent posterior single open-door laminoplasty in the Department of orthopedics of our hospital from January 2020 to January 2021 as the study subjects. In the experimental group, quality control circle activities were used to prepare the surgical instruments before operation, including 32 males and 18 females, with an average age of 58.3 ± 10.5 years; The control group did not use quality control circle activities to prepare the surgical instruments before operation, including 27 males and 22 females, with an average age of 60.5 ± 9.8 years. First, the “quality control circle” activity group was established to carry out quality control circle activity steps such as theme selection, plan formulation, status analysis, goal establishment, problem rectification, specific implementation, effect evaluation and effect evaluation. The database was established by software, and the t-test and chi square test were used for statistical analysis to compare the pre-operative instrument preparation rate of the two groups of patients undergoing cervical posterior single open-door laminoplasty. Finally, the improvement of team consciousness, nursing knowledge, nursing quality, consciousness response and other qualities of all circle members in the experimental group before and after the use of quality control circle activities were analyzed, and the clinical satisfaction of patients and their families, anesthesiologists and chief surgeons with the operation and the integrity rate of equipment preparation were compared between the two groups.

    Results: The overall integrity rate of the instruments in the experimental group was 90%, and the overall integrity rate of the instruments in the control group was 74%. The integrity rate of the instruments in the experimental group was significantly higher than that in the control group (P < 0.01). After the implementation of quality control circle activities, the team consciousness, nursing knowledge, nursing quality and consciousness reaction of the circle members in the experimental group were significantly improved compared with those before the implementation of quality control circle activities, and the difference between the two groups was statistically significant (P < 0.01). The overall satisfaction of patients and their families, anesthesiologists, and chief surgeons in the experimental group was 92%, 88%, and 90%, and that of the control group was 76%, 68%, and 74%, respectively. The overall satisfaction of the experimental group was significantly higher than that of the control group (P < 0.05); The integrity rate of surgical instruments preparation in the experimental group was 90%, and that in the control group was 74%. The experimental group was significantly higher than the control group (P < 0.01).

    Conclusion: The application of quality control circle activities can improve the integrity of instrument preparation for posterior cervical surgery, improve the satisfaction of patients, family members and medical staff, and improve the quality of surgical care.

    Aurelian Udristioiu, Adina Martin, Alexandru Giubelan, Papurica Maria Daniela, Maria Daniela, Liviu Martin, and Delia Nica- Badea


    The lifespan of a cell in the body oscillates between two fundamental processes, Autophagy, which ensures cell survival, even under conditions of cellular stress, and Apoptosis, which programs the end of cell life, not before the renewal of a new cell in a tissue. Overall, there is a continuation of daily life until a specified date of highlighting the length of the telomeres, in the chromosomal analysis of the cell.

    Apoptosis, in the scheduling of cell life, is a normal process which is different from cell necrosis that occurs as a result of physical or chemical aggression. The decision to activate a suicide process is made based on intrinsic or extrinsic apoptotic messages. The intrinsic inducers of apotheosis come from the mitochondria or nucleus. Extrinsic inducers of apotheosis are ligands, cytokines for death receptors, (DR-Death receptors) on each cell surface.

    Autophagy: is a homeostatic and catabolic processes that allows the sequestration and lysosomal degradation of cytoplasmic organs and proteins, important for maintaining genomic stability and cell survival. Autophagy is regulated by the Beclin 1 protein, which forms a complex with a class III enzyme, phospho-inoside 3-kinase (PI3K), and serves as a platform for the recruitment of other proteins critical for autophagosome formation.

    Conclusions: The most important regulatory mechanism in autoimmunity and oncogenesis process are death receptors, caspases, mitochondria, the Bcl-2 family proto-oncogenes and tumor suppressor gene P53. Pharmacological manipulation of autophagy for cancer prevention and treatment will depend on our ability to successfully recognize the functional status of autophagy in tumors, and the availability of specific autophagic modulators.

    Vako Ilda, Eirini Patsaki, Alexandros Kouvarakos, Vaios Grammatis, Ioannis Kouroutzis, Theodora Paisia Apostolidi, Vasiliki Roka, Anastasia Kotanidou, Pavlos Sarafis, and Maria Malliarou


    Healthcare professionals during the pandemic in the Greek public healthcare system have experienced increased psychological distress, fear and a greater intention to quit their jobs. This study analyzes the factors of moral distress and moral resilience of healthcare professionals employed during the second wave of the pandemic. The target group was the healthcare professionals (HP = 169) who served in the Evaggelismos General Hospital Covid-clinics and -ICU for 2022 and data were collected through life protocols.


    Healthcare professionals believe that when faced with moral challenges, they are able to discern them and think clearly. They are especially stressed when they care for more patients than they can safely handle when they are involved in care that causes unnecessary suffering or does not adequately relieve pain or symptoms, and when they notice that patient care is getting worse. Also stressful are the situations, leading to the creation of possible moral distress, when they witness a violation of a standard of practice or moral code. Factors that lead or may lead healthcare professionals to moral distress are nursing safety, unnecessary and deteriorating patient care, and violation of medical confidentiality, violation of standards of practice or moral codes.


    The score on the MMD-HP scale indicates low-to-moderate levels of moral distress. Based on the RMRS scale the moral resilience of healthcare professionals is characterized by moderate-to-high with the highest scores per statement seen when patient care is getting worse and feel pressured to ignore situations where patients have not been given adequate information. The healthcare professionals report that they have either left or have considered leaving their position in a clinic due to moral distress, although they are not currently thinking of leaving their position. The factors that increase the frequency of moral distress and decrease their moral resilience are feeling powerless anxiety, nursing/treatment errors, aggressive treatment, caring for more patients than they can handle, substandard patient care, and hierarchical teams.

    Soumya Sonalika, Sushree Sangita Mishra, Subhashree Mahapatro, and Devasmita Sahoo


    Introduction: Breast cancer is a global health concern, accounting for significant morbidity and mortality among women. The fragile ill prepared healthcare systems in low- & middle-income countries need to address these challenges find solutions with their limited resources.

    Objectives: Through a critical examination of the literature, this article aims to contribute to a better understanding of breast cancer and to stimulate further research in this field.

    Methods & Analysis: This review article provides an in-depth analysis of the current state of breast cancer research, focusing on advancements in diagnosis, treatment, and prevention, as well as the challenges and future directions.

    Conclusion: Emerging technologies, such as AI, 3D bioprinting, and nanotechnology, hold promise for addressing the challenges like management of metastatic disease, global disparities in outcomes, and the need for a better understanding of breast cancer etiology and revolutionizing breast cancer care.

    Kah Lee and Jennifer Loke


    Background: Obtaining appointments at a general practice was critical for reducing avoidable hospital admissions, and ultimately saving healthcare costs. In the United Kingdom (UK), problematic access of appointments at individual general practices persisted resulting from increasing health complexities in primary care, which were exacerbated by shortages of medical doctors as general practitioners (GP). The UK government pursued the employing of care-coordinators at primary care networks to allocate care to non-GP health professionals as a solution, but patient demand for GP appointments at individual practices continued to surge.

    Aims: This paper reports on an investigation of the ideal way to address patient demand on GP appointments at individual practices. It aimed to report on the effects of two newly implemented joint consultations, one comprising a nursing team and another, a multi-disciplinary team comprising medical doctors and nursing personnel.

    Methods: Three reviews were conducted in a 3500 patient-list-sized GP practice located in North-Eastern part of England. The aim was to analyse retrospective data of the telephony system to explore the effect of joint consultations on demand of GP appointments that were made through the telephony system. The number and lengths of incoming telephone calls to secure GP or nursing appointments at the practice were analysed descriptively. The periods of analysis were from January to August in the years 2021, 2022 and 2023.

    Results: Since implementation of the two joint consultations, there was a 32% reduction in telephone calls for GP appointments. There was also a shortening of the duration of these telephone calls and decreasing trends of missed calls. The increased lengths of calls towards the tail end of the 3rd review period in 2023 demonstrated increased patient awareness and cooperation for in-depth discussions about their symptoms prior to securing appointments.

    Conclusions: The joint consultations had significantly decreased patient demands for GP appointments via telephone. In addition, the joint consultations had not only allowed holistic care needs to be addressed, but also, they had permitted appropriate care to be delivered in a timely fashion. It is therefore important to ensure appropriate healthcare funding to support the implementation of joint consultations at individual GP practices.

    Thaisa Mara Leal Cintra Rodrigues, Rita de Cássia de Marchi Barcellos Dal, and Carla Aparecida Arena Ventura


    Background: The post-pandemic historical moment of COVID-19 has had consequences on the mental health of workers, evidenced by the growing statistics of depression, anxiety, suicidal ideation, panic syndrome, burnout syndrome, psychotic episodes, alcohol and drug addiction, stress, fatigue, and professional exhaustion.

    Aims: Analyse the recommendations of the International Labour Organization and the Brazilian laws applicable to occupational mental health to identify documents that address intervening laws in workers’ mental health in the international scientific literature and introduce Bill 3,588/2020, which aims to regulate occupational psychosocial risks.

    Methods: Narrative review of the scientific literature in the databases Scopus, Lilacs BVS, PubMed, Cinhal, and Ebesco and document analysis of Brazilian legislation and international recommendations on workers’ mental health and norms related to exposure to occupational psychosocial risks and measures of intervention in mental health.

    Results: The International Labour Organization established three Conventions to protect workers’ health. In the Brazilian legal system, six broad and general norms were identified. The narrative prediction resulted in nine intervening laws that address the worker’s mental health. Conclusion: In Brazil, there is no specific legislation regarding the worker’s right to mental health, nor any regulation through Regulatory Norms, which demonstrates the need for the approval of Bill 3,588/2020, pending in the National Congress, which aims at regulating psychosocial risks, such as intervention, management, and prevention measures capable of minimizing mental illness at work.

    Regina Jillapalli, Kavita Radhakrishnan, Lorraine Walker, Jane D Champion, and Matthew McGlone


    Background: Asian Indians, primarily through immigration, are among the three fastest growing Asian minority populations in the United States. Sadly, Asian Indian Women did not meet the Health People 2020’s the 93% cervical cancer screening goal of 93%. Cervical cancer screening rates among Asian Indian Women were 70.5% compared to 82.7% among non-Hispanic Whites. A systematic review revealed the need for qualitative studies to explore influences of cultural beliefs on cervical cancer screening (pap smears) behaviors among Asian Indian Women applying symbolic interactionism theoretical framework.

    Purpose: To explore the influence of cultural beliefs on cervical cancer screening behaviors among Asian Indian Women.

    Method: A qualitative descriptive ethnographic design used descriptive ethosemantic semi-structured questions to investigate cultural impact on cervical cancer prevention behaviors among a purposive sample of 15 Asian Indian Women between the ages 21 to 49 years of age. Data analysis used inductive analytical methods.

    Findings: Five themes influenced cervical cancer screening: locus of control, concept of health, ‘no sex before marriage,’ awareness, and body image. A healthy internal locus of control, sense of being healthy, awareness, and positive body image supported cervical cancer screening behaviors. An external locus of control, belief that health is not a priority, “no sex before marriage,” and low body image were barriers to cervical cancer screening behaviors. Additionally, the concept of “no sex before marriage” influenced timing of the first pap smear. Notwithstanding their cultural beliefs, employment, health insurance, and recommendations from their providers had a positive impact on cervical cancer screening.

    Conclusion: Findings from this study have implications for both health policy and clinical practice. Health policy influences funding for basic screening and preventive services. Clinical practice implications encompass fostering partnerships within the community to promote prevention programs and cultural sensitivity training for providers. Future community-based participatory research should address interventional studies to increase compliance for cervical cancer screening and prevention behaviors among Asian Indian Women.

    Challenges and Opportunities in Coronary Artery Disease

    Challenges and Opportunities in Coronary Artery Disease

    Jacques Fair, Esperanza Acuna, and Robert Roberts


    Coronary artery disease (CAD) is the number one cause of death in the world. It is estimated that 50% of Americans will experience a cardiac event in their lifetime. The underlying pathology leading to coronary artery disease and its clinical manifestations, such as angina, myocardial infarction, and sudden death, is coronary atherosclerosis. While the disease is not usually manifested clinically until the sixth or seventh decade, the underlying pathology is initiated as early as the second or third decade. Numerous randomized clinical trials have shown cardiac morbidity and mortality can be prevented by lowering the risk of known conventional risk factors for CAD, such as decreasing plasma cholesterol or controlling hypertension. Secondary prevention of these conventional risk factors has been very effective; however, primary prevention has been shown to be even more effective. A major barrier to primary prevention is the lack of markers to detect among young, asymptomatic individuals at risk for CAD. The conventional risk factors are often not present until the sixth or seventh decade, which could be late for primary prevention. Genetic predisposition accounts for 50% of the risk for CAD. Recently, over 200 genetic risk variants predisposing to CAD have been discovered. Based on these variants, one can express the genetic risk for CAD in a single number referred to as the Polygenic Risk Score (PRS). The PRS has been evaluated in over one million individuals and shown that those with high genetic risk have the highest incidence of heart disease and can be reduced by 40–50% by utilizing drugs (statins and PCSK9 inhibitors) or lifestyle changes (a favorable diet and increased exercise). The genetic risk for CAD is determined at conception and thus can be predicted anytime from birth onward. The PRS detection of young, asymptomatic individuals based on the PRS enables one to implement early primary prevention. Adoption of the PRS to risk stratify for CAD could represent a paradigm shift in the prevention of this pandemic disease.

    Robert Roberts and Esperanza Acuna


    Coronary artery disease, the number one cause of death in the world, is highly amenable to primary and secondary prevention. Primary prevention is limited because of a lack of biomarkers to detect CAD in its asymptomatic phase. Conventional risk factors, such as hypertension, are not evident until the 6th or 7th decade, which may be late for primary prevention, particularly in males. The recent discovery of genetic risk variants for CAD has the potential, through risk stratification, to detect individuals most appropriate for primary prevention. First, genetic risk accounts for about 50% of predisposition to CAD; second, it is determined at conception and not influenced by age since DNA does not change in one’s lifetime. Thirdly, genetic risk can be determined at any time from birth onward, which is close to ideal for early primary prevention. A review of the literature shows genetic risk can be summarized in a single number, referred to as the polygenic risk score (PRS), and used to stratify risk for CAD. The PRS has been evaluated in over 1 million individuals, and those in the top 20% exhibit a one-to-four-fold greater risk for CAD than those in the bottom 20%. More importantly, clinical studies have shown that decreasing plasma LDL-C or modifying lifestyle decreases the genetic risk for CAD by 50%. The polygenic risk score, obtained from a single blood sample, does not need to be repeated in one’s lifetime. Furthermore, the genetic risk captured by the PRS is relatively independent of conventional risk factors, including family history. The current PRS was determined primarily for individuals of European decent, which can be a limitation to its use in other ethnic groups. However, the results of trials ongoing in several ethnic groups will soon be available. We propose that primary prevention be initiated early in life in individuals in the top 20% of the PRS. The test is relatively inexpensive, and generic drug therapy is also inexpensive. The use of the PRS to risk stratify for CAD would be a paradigm shift for the implementation of early primary prevention of CAD.

    Lisa Ferraz, Andreia Fernandes, Ana Faustino, Simão Carvalho, Adriana Pacheco, and Ana Neves


    Background: Although dobutamine stress echocardiography (DSE) has a high specificity, there is still a subset of patients with false positive tests (FP); whether these results have prognostic value remains unclear.

    Aims: To identify the clinical and echocardiographic predictors of FP on DSE and to evaluate the prognostic impact of FP on DSE.

    Methods: Retrospective study of 355 consecutive patients who underwent DSE for ischemia assessment over a one-year period: 134 (37,7%) women, 70,3 ± 0,57 years. Demographics, risk factors, clinical and laboratory parameters, and DSE variables were evaluated. Patients were divided into 2 groups regarding the presence (FP+) or absence (FP0) of an FP result on DSE, and a comparative analysis was performed to characterize the groups and identify potential predictors of FP results. Patients were followed for 2 years to assess acute myocardial infarction, hospitalization for acute heart failure (HF), and mortality.

    Results: The FP rate was 4.5%. Compared to FP0, patients in group FP+ were younger, baseline wall motion abnormalities were more frequent, they had higher mean blood pressure values at rest and peak stage, and they often had a hypertensive response. There were no significant differences regarding previous coronary artery disease, medication, or a complete left bundle branch block. By multivariate analysis, only mean blood pressure values at rest (OR 0,01; 95%CI 0,005-0,02; p=0,003) and at peak stage (OR 0,02; 95%CI 0,000-0,004; p=0,003) were independent predictors of FP. During follow-up, acute myocardial infarction (FP+: 12.5% vs. FP0: 1.8%, p = 0.046), HF (FP+: 6.3% vs. FP0: 11.5%, p = 0.44), and mortality (FP+: 6.3% vs. FP0: 6.2%, p = 0.65). After adjustment for age, sex, and comorbidities, there were no differences between the groups regarding HF and mortality, but the group FP+ maintained a higher rate of acute myocardial infarction (OR 0,21; 95%CI 0,065-0,354; p = 0,005).

    Conclusion: The AFP result on DSE was associated with higher mean blood pressure values during the test and higher rates of acute myocardial infarction during follow-up. Therefore, this result on DSE should be used as a risk marker for ischemic events. It can identify patients who may benefit from aggressive risk factor control and careful clinical follow-up.

    Gerald Dorros, M.D., FACC


    The unintended consequences of the US Centers for Medicare & amp; Medicaid Services’ (CMS) decision not to pay for invasive diagnostic FFR (Fractional Flow Reserve) have precluded its routine diagnostic use in hundreds of thousands of Medicare beneficiaries who suffered inappropriate coronary stent procedures (PCI) that worsened Medicare beneficiaries’ clinical outcomes: 20% of PCI patients have no or uncertain clinical indications but are nevertheless operated upon, and 33% of potential PCI stenoses are non-ischemic and require no PCI. These unnecessary PCIs, often confounded by aging’s anatomical and comorbid complexities, result in preventable complications, repeat procedures, worse clinical outcomes, unwarranted deaths, and an avoidable $1 billion annual expenditure. The best coronary artery disease (CAD) patient care requires astute clinical assessment coupled with diagnostic physiologic ischemic lesion categorization, which directly links lesion treatment to patient management. CMS’ unrealistic expectation that their bundled payment to a single healthcare provider would motivate providers to maximize their profits through efficiently coordinated and improved care was naive; this foolish policy of eschewing invasive FFR payments and expecting providers to absorb the FFR pressure wire’s cost has inflicted potential irreparable harm on all Medicare beneficiaries. CMS has forsaken its mission to attain the “highest level of health for all people, where everyone has a fair and just opportunity to attain their optimal health regardless of race, ethnicity, disability, sexual orientation, gender identity, socioeconomic status, geography, preferred language, or other factors that affect access to care and health outcomes”.

    George Trad, MD, Rasiq Zackria, DO, Syed Abdul Basit, MD, and John K. Ryan, MD


    Necrotizing pancreatitis (NP) is a life-threatening complication of acute pancreatitis. It requires an extended hospital stay, aggressive management, and a higher risk of mortality. Risk factors such as comorbidities in the patient’s history, including a history of coronary artery disease and cerebrovascular disease, can increase the risk of developing necrotizing pancreatitis. The presentation of necrotizing pancreatitis is similar to acute pancreatitis, but specific labs such as hematocrit levels can be monitored to anticipate the development of necrotizing pancreatitis.  In addition, diagnostic imaging must be obtained to classify necrotizing pancreatitis and aid in management choice. Fluid hydration, adequate pain management, and nutritional support are the principles of treating necrotizing pancreatitis. Deciding whether to drain the necrotic collection or not is usually determined based on the type of necrosis present and whether it is infected.  Infected necrotizing pancreatitis can also occur, and patients usually need to be monitored closely with appropriate antibiotics for a long duration. Patients affected by necrotizing pancreatitis can potentially develop complications that can lead to devastating outcomes. Necrotizing pancreatitis complications can occur due to an inflammatory reaction on the adjacent structure, such as splanchnic vein thrombosis, gastrointestinal fistula, or an inflammatory reaction within the pancreas leading to an exocrine and an endocrine pancreatic insufficiency. We present here a literature review of necrotizing pancreatitis and the complications that can arise from it.

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