Sex differences in pulmonary and systemic vascular function at rest and during exercise in healthy middle-aged adults.

Our aim was to conduct a sex-disaggregated analysis of pulmonary and systemic vascular function in healthy individuals both at rest and during submaximal exercise. Healthy individuals underwent right-heart catheterization at rest and during submaximal cycling. Hemodynamic data were collected in a control state and with moderate exercise. Pulmonary and systemic vascular variables including: compliance, resistance, and elastance were calculated, indexed to body surface area (BSA), adjusted for age and compared between male and female sex. Thirty-six individuals (18M/18F; 54 ± 7 vs. 58 ± 6 years, p = 0.04) were included. When adjusted for age and indexed to BSA, total pulmonary resistance (TPulmR) (516 ± 73 vs. 424 ± 118 WU m-2, p = 0.03) and pulmonary arterial elastance (PEa) (0.41 ± 0.1 vs. 0.32 ± 0.1 mmHg ml-1 m2, p = 0.03) were higher in females vs. males. Both pulmonary (Cpa) and systemic compliance (Csa) were lower in females vs. males however lost significance with adjustment for age. Systemic arterial elastance (SEa) was higher in females (1.65 ± 0.29 vs. 1.31 ± 0.24 mmHg ml-1, p = 0.05). Secondary analyses demonstrated significant correlations between age and PVR (r = 0.33, p = 0.05), TPulmR (r = 0.35, p = 0.04), Cpa (r = -0.48, p < 0.01), and PEa (r = 0.37, p = 0.03). During exercise, there were greater increases in TPulmR (p = 0.02) and PEa (p = 0.01) in females vs. males. In conclusion, TPulmR and PEa are significantly higher at rest and exercise in females vs. males. Cpa and Csa were lower in females, however this may have been confounded by age. Our results are consistent with the notion that indices of pulmonary and systemic vascular load are higher, related to both older age and female sex, independent of heart failure.

Safety and Efficacy of Glucagon-Like Peptide-1 Receptor Agonists in Children and Adolescents with Obesity: A Meta-Analysis.

OBJECTIVES: To determine the weight, body mass index (BMI), cardiometabolic, and gastrointestinal effects of glucagon-like peptide-1 (GLP-1) receptor agonists in children with obesity. STUDY DESIGN: Web of Science, PubMed/MEDLINE, and Scopus databases from 01/01/1994-01/01/2021 for randomized control trials examining the weight, BMI, cardiometabolic, or gastrointestinal effects of GLP-1 receptor agonists in children and adolescents with obesity. Data were extracted by 2 independent surveyors and a random effects model was applied to meta-analyze generic inverse variance outcomes. Primary outcomes were related to weight and cardiometabolic profile, and secondary outcomes of interest were gastrointestinal-related treatment-emergent adverse events. RESULTS: Nine studies involving 574 participants were identified, of which 3 involved exenatide and 6 involved liraglutide. GLP-1 receptor agonists use caused a modest reduction in body weight (mean difference [MD] -1.50 [-2.50,-0.50] kg, I2 64%), BMI (MD -1.24 [-1.71,-0.77] kg/m2, I2 0%), and BMI z score (MD -0.14 [-0.23,-0.06], I2 43%). Glycemic control was improved in children with proven insulin resistance (glycated hemoglobin A1c MD -1.05 [-1.93,-0.18] %, I2 76%). Although no lipid profile improvements were noted, a modest decrease in systolic blood pressure was detected (MD -2.30 [-4.11,-0.49] mm Hg; I2 0%). Finally, analysis of gastrointestinal-related treatment-emergent adverse events revealed an increased risk of nausea (risk ratio 2.11 [1.44, 3.09]; I2 0%), without significant increases in other gastrointestinal symptoms. CONCLUSIONS: This meta-analysis indicates that GLP-1 receptor agonists are safe and effective in modestly reducing weight, BMI, glycated hemoglobin A1c, and systolic blood pressure in children and adolescents with obesity in a clinical setting, albeit with increased rates of nausea. PROSPERO ID: CRD42020195869.

Journey into the unknown: considering the international medical graduate perspective on the road to Canadian residency during the COVID-19 pandemic.

The COVID-19 pandemic has had a tremendous effect on education programs worldwide, including medical education. Particularly, International Medical Graduates (IMGs) planning to pursue residency training in Canada have been profoundly impacted. Cancellation of away electives, as well as changes to the format, timeline, and requirements of mandatory medical licensing exams has left IMG residency applicants in uncharted territory. Given that IMGs comprise up to 25% of the Canadian healthcare force, and often are based in underserviced areas, the licensure and eligibility of IMGs to continue to enter the Canadian healthcare force is of the utmost importance in the midst of the COVID-19 pandemic. As the pandemic evolves, it is imperative that key decision makers and stakeholders continue to consider the downstream effect for IMGs and their eligibility to practice in Canada.

La pandémie de la COVID-19 a fortement affecté les programmes d'éducation dans le monde entier, y compris l'éducation médicale. En particulier, les diplômés internationaux en médecine (DIM) qui prévoyaient s'inscrire à un programme de résidence au Canada ont été profondément touchés. L'annulation des stages à l'étranger, ainsi que les changements apportés au format, au calendrier et aux exigences des examens requis pour l'obtention du permis d'exercice de la médecine ont laissé en territoire inconnu les candidats internationaux aux programmes de résidence. Étant donné que les DIM représentent jusqu'à 25 % des professionnels de la santé au Canada et qu'ils exercent souvent dans les régions mal desservies, l'octroi de permis d'exercice et le recrutement de DIM dans le réseau de la santé canadien revêtent une importance capitale en contexte de pandémie de la COVID-19. À mesure que la pandémie évolue, il est impératif que les principaux décideurs et intervenants continuent de tenir compte des effets néfastes qu'elle peut avoir pour les DIM et leur admissibilité à l'exercice de la profession au Canada.

Characterization of troponin I levels post synchronized direct current cardioversion of atrial arrhythmias in patients with and without cardiomyopathy.

BACKGROUND: Cardiac-specific markers of myocardial injury, such as troponin I (TnI), are often elevated following procedures that stimulate the myocardium. This study aimed to determine the effect of synchronized direct current (DC) cardioversion of atrial arrhythmias on myocardial injury 6-h post-procedure, as measured by cardiac TnI in patients with and without cardiomyopathy. METHODS: Seventy-three individuals (59 M:14 F) participated in this study. Inclusion criteria were subjects 18 and older undergoing DC cardioversion for an atrial arrhythmia, including elective and non-elective admissions. Exclusion criteria included MI or CABG within the past month, cardioversion for a ventricular arrhythmia, or recent shock by implantable internal cardioverter defibrillator. Patients underwent standard DC cardioversion procedure with blood work (TnI and CRP) prior to and 6-h post-cardioversion. Primary outcome was change in TnI. Secondary outcomes included changes in CRP, correlation of TnI with cumulative energy and LVM, and a sub-group analysis in patients with cardiomyopathy. RESULTS: There was no significant change in TnI following cardioversion (20.4 ± 7.9 vs. 17.5 ± 6.5 ng/L, F(1,72) = 2.651, p = 0.108). When stratified by cardiomyopathy status, there was a statistically significant reduction in TnI following cardioversion in the non-cardiomyopathy group (6.7 ± 3.7 ng/L vs. 6.2 ± 3.2 ng/L, F(1,58) = 6.481, p = 0.014) and a clinically significant reduction in the cardiomyopathy group (74.4 ± 136.7 ng/L vs. 54.6 ± 104.3 ng/L, F(1,13) = 3.676, p = 0.07). There was no significant relationship between change in TnI and cumulative energy or LVM (r = 0.137, p = 0.306 and r = 0.125, p = 0.412 respectively). CONCLUSIONS: Synchronized DC cardioversion of an atrial arrhythmia did not cause myocardial injury 6-h post-cardioversion. Sub-group analysis suggests that cardioversion of patients with cardiomyopathy may result in normalization of TnI levels.

Effect of bariatric surgery on circulating FGF-19: A systematic review and meta-analysis.

Fibroblast growth factor-19 (FGF-19) is a gut hormone which interacts with metabolism and is depleted in obesity. There is some indication that the hormone undergoes a resurgence following bariatric surgery (BS), an effect which may contribute to the beneficial outcomes of such procedures. This systematic review and meta-analysis aims to synthesize the available literature on FGF-19 levels before and after BS. MEDLINE, Scopus and Web of Science databases were searched, and the effect of different surgical procedures and degrees of body mass index (BMI) reduction on FGF-19 levels was assessed by DerSimonian and Laird random-effects model in meta-analysis and dose-response analyses. This meta-analysis, which included 474 patients from 25 arms undergoing one of five BS procedures, revealed a significant increase in the levels of circulating FGF-19 following all-type BS. Vertical sleeve gastrectomy, duodenal-jejunal bypass liner and Roux-en-Y gastric bypass all significantly increased circulating FGF-19 levels from baseline. However, gastric banding failed to achieve the same, and in fact, biliopancreatic diversion was associated with decreased circulating FGF-19. Finally, an inverse association between FGF-19 and the degree of BMI-reduction post-operatively was noted. FGF-19 is increased by BS and may represent a pharmaceutical target in efforts to reproduce the beneficial effects of BS in a medical setting.

Absence of resting cardiovascular dysfunction in middle-aged endurance-trained athletes with exaggerated exercise blood pressure responses.

OBJECTIVE: Untrained individuals with exaggerated blood pressure (EBP) responses to graded exercise testing are characterized as having resting dysfunction of the sympathetic and cardiovascular systems. The purpose of this study was to determine the resting cardiovascular state of endurance-trained individuals with EBP through a comparison of normotensive athletes with and without EBP. METHODS: EBP was defined as a maximal systolic blood pressure (SBP) at least 190 mmHg and at least 210 mmHg for women and men respectively, in response to a graded exercise test. Twenty-two life-long endurance-trained athletes (56 ±â€Š5 years, 16 men) with EBP (EBP+) and 11 age and sex-matched athletes (55 ±â€Š5 years, eight men) without EBP (EBP-) participated in the study. Sympathetic reactivity was assessed using BP responses to a cold pressor test, isometric handgrip exercise, and postexercise muscle ischemia. Resting left ventricular structure and function was assessed using two-dimensional echocardiography, whereas central arterial stiffness was assessed using carotid-to-femoral pulse wave velocity. Calf vascular conductance was measured at rest and peak postexercise using strain-gauge plethysmography. RESULTS: All sympathetic reactivity, left ventricular, and arterial stiffness indices were similar between groups. There was no between-group difference in resting vascular conductance, whereas peak vascular conductance was higher in EBP+ relative to EBP- (1.81 ±â€Š0.65 vs. 1.45 ±â€Š0.32 ml/100 ml/min/mmHg, P < 0.05). CONCLUSION: Findings from this study suggest that athletes with EBP do not display the resting cardiovascular state typically observed in untrained individuals with EBP. This response in athletes, therefore, is likely a compensatory mechanism to satisfy peripheral blood-flow demands rather than indicative of latent dysfunction.