From Bench to Bedside: Experiencing the Transition from Scientist to Medical Student

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Is adipose tissue a reservoir for viral spread, immune activation and cytokine amplification in COVID-19?

Coronavirus disease 2019 (COVID-19), the worst pandemic in more than a century, has claimed >125,000 lives worldwide to date. Emerging predictors for poor outcome include advanced age, male gender, pre-existing cardiovascular disease and risk factors including hypertension, diabetes and more recently obesity. Herein, we posit new obesity-driven predictors of poor COVID-19 outcome, over and above the more obvious extant risks associated with obesity including cardiometabolic disease and hypoventilation syndrome in intensive care patients. We outline a theoretical mechanistic framework whereby adipose tissue in subjects with obesity may act as a reservoir for more extensive viral spread with increased shedding, immune activation and cytokine amplification. We propose studies to test this reservoir concept with a focus on specific cytokine pathways that might be amplified in subjects with obesity and COVID-19. Finally, we underscore emerging therapeutic strategies that might benefit subsets of patients in which cytokine amplification is excessive and potentially fatal

Probiotics and non-alcoholic fatty liver disease in children and adolescents: a systematic review

Background: Non-Alcoholic Fatty Liver Disease (NAFLD) in childhood is an increasing public health issue globally with significant long-term consequences. NAFLD management mainly consists of lifestyle modifications, however, adjunct pharmacological therapies are currently lacking. Gut microbiota manipulation via probiotics may alter the course of pediatric NAFLD. The objective of this systematic review was to synthesise all the available literature on the use of probiotics in children and adolescents with NAFLD. Methods: We systematically searched PubMed, EBSCOhost, Scopus, Web of Science, and Cochrane Library for trials on the use of probiotics in pediatric NAFLD. A quantitative DerSimonian Laird random effects meta-analysis was performed when possible; otherwise, a narrative summary of the study outcomes was presented and discussed. A separate search was completed to include all the ongoing registered trials on probiotics use in pediatric NAFLD. Results: 5 randomized controlled trials met the inclusion criteria. Of these, 4 trials were included in the final quantitative analysis. Probiotic therapy significantly reduced the levels of ALT (mean difference, -10.39 [-19.85, -0.93]), however significant heterogeneity between studies was identified (I2, 93%). Conclusions: There is insufficient evidence to support probiotics in the treatment of pediatric NAFLD given the substantial degree of discordance amongst the available trials. Lifestyle modifications focusing on maintaining a normal BMI and regular exercise continue to be the gold standard approach to treating NAFLD in children

Global, regional, and national progress towards Sustainable Development Goal 3.2 for neonatal and child health: all-cause and cause-specific mortality findings from the Global Burden of Disease Study 2019

Background Sustainable Development Goal 3.2 has targeted elimination of preventable child mortality, reduction of neonatal death to less than 12 per 1000 livebirths, and reduction of death of children younger than 5 years to less than 25 per 1000 livebirths, for each country by 2030. To understand current rates, recent trends, and potential trajectories of child mortality for the next decade, we present the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 findings for all-cause mortality and cause-specific mortality in children younger than 5 years of age, with multiple scenarios for child mortality in 2030 that include the consideration of potential effects of COVID-19, and a novel framework for quantifying optimal child survival. Methods We completed all-cause mortality and cause-specific mortality analyses from 204 countries and territories for detailed age groups separately, with aggregated mortality probabilities per 1000 livebirths computed for neonatal mortality rate (NMR) and under-5 mortality rate (USMR). Scenarios for 2030 represent different potential trajectories, notably including potential effects of the COVID-19 pandemic and the potential impact of improvements preferentially targeting neonatal survival. Optimal child survival metrics were developed by age, sex, and cause of death across all GBD location-years. The first metric is a global optimum and is based on the lowest observed mortality, and the second is a survival potential frontier that is based on stochastic frontier analysis of observed mortality and Healthcare Access and Quality Index. Findings Global U5MR decreased from 71.2 deaths per 1000 livebirths (95% uncertainty interval WI] 68.3-74-0) in 2000 to 37.1 (33.2-41.7) in 2019 while global NMR correspondingly declined more slowly from 28.0 deaths per 1000 live births (26.8-29-5) in 2000 to 17.9 (16.3-19-8) in 2019. In 2019,136 (67%) of 204 countries had a USMR at or below the SDG 3.2 threshold and 133 (65%) had an NMR at or below the SDG 3.2 threshold, and the reference scenario suggests that by 2030,154 (75%) of all countries could meet the U5MR targets, and 139 (68%) could meet the NMR targets. Deaths of children younger than 5 years totalled 9.65 million (95% UI 9.05-10.30) in 2000 and 5.05 million (4.27-6.02) in 2019, with the neonatal fraction of these deaths increasing from 39% (3.76 million 95% UI 3.53-4.021) in 2000 to 48% (2.42 million; 2.06-2.86) in 2019. NMR and U5MR were generally higher in males than in females, although there was no statistically significant difference at the global level. Neonatal disorders remained the leading cause of death in children younger than 5 years in 2019, followed by lower respiratory infections, diarrhoeal diseases, congenital birth defects, and malaria. The global optimum analysis suggests NMR could be reduced to as low as 0.80 (95% UI 0.71-0.86) deaths per 1000 livebirths and U5MR to 1.44 (95% UI 1-27-1.58) deaths per 1000 livebirths, and in 2019, there were as many as 1.87 million (95% UI 1-35-2.58; 37% 95% UI 32-43]) of 5.05 million more deaths of children younger than 5 years than the survival potential frontier. Interpretation Global child mortality declined by almost half between 2000 and 2019, but progress remains slower in neonates and 65 (32%) of 204 countries, mostly in sub-Saharan Africa and south Asia, are not on track to meet either SDG 3.2 target by 2030. Focused improvements in perinatal and newborn care, continued and expanded delivery of essential interventions such as vaccination and infection prevention, an enhanced focus on equity, continued focus on poverty reduction and education, and investment in strengthening health systems across the development spectrum have the potential to substantially improve USMR. Given the widespread effects of COVID-19, considerable effort will be required to maintain and accelerate progress. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd

Inside the skin of a patient with diabetes: fostering cognitive empathy through insulin pump simulation

Implication Statement: In order to best treat a patient, the carer must be able to clearly see their point of view. In the case of the complexities of insulin pump therapy, physicians may not fully understand the common challenges that drive patients to non-adherence. The author undertook a three-day simulation using wearable technology to explore this experience. This form of simulation represents a simple yet effective means by which to foster cognitive empathy in undergraduate and postgraduate medical education settings alike.Énoncé des implications de la recherche : Pour offrir le meilleur traitement possible, le soignant doit être en mesure de voir les choses du point de vue du patient. Or, les médecins pourraient ne pas comprendre les défis courants liés à la complexité du traitement par pompe à insuline qui expliquent la non-observance thérapeutique chez les patients. L'auteur a mené une simulation de trois jours pour explorer l’expérience de ce traitement à l’aide d’une technologie portable. Cette forme de simulation constitue un moyen simple et efficace pour favoriser l'empathie cognitive dans les établissements d'enseignement médical prédoctoral et postdoctoral