Host Genetics and Antiviral Immune Responses in Adult Patients With Multisystem Inflammatory Syndrome.

COVID-19 associated multisystem inflammatory syndrome (MIS) is a rare condition mostly affecting children but also adults (MIS-A). Although severe systemic inflammation and multiorgan dysfunction are hallmarks of the syndrome, the underlying pathogenesis is unclear. We aimed to provide novel immunological and genetic descriptions of MIS-A patients. Cytokine responses (IL-6, IL-1ß, TNFα, CXCL10, type I, II and III interferons) following SARS-CoV-2 infection of peripheral blood mononuclear cells in vitro were analyzed as well as antibodies against IFNα and IFNω (by ELISA) in patients and healthy controls. We also performed whole exome sequencing (WES) of patient DNA. A total of five patients (ages 19, 23, 33, 38, 50 years) were included. The patients shared characteristic features, although organ involvement and the time course of disease varied slightly. SARS-CoV-2 in vitro infection of patient PBMCs revealed impaired type I and III interferon responses and reduced CXCL10 expression, whereas production of proinflammatory cytokines were less affected, compared to healthy controls. Presence of interferon autoantibodies was not detected. Whole exome sequencing analysis of patient DNA revealed 12 rare potentially disease-causing variants in genes related to autophagy, classical Kawasaki disease, restriction factors and immune responses. In conclusion, we observed an impaired production of type I and III interferons in response to SARS-CoV-2 infection and detected several rare potentially disease-causing gene variants potentially contributing to MIS-A.

Coffee consumption and work satisfaction among Scandinavian anaesthesiologists: A survey.

BACKGROUND: It is a common prejudice that anaesthetic doctors are believed to have high coffee consumption. In this study, we aimed to assess the association between coffee drinking and work satisfaction among Scandinavian anaesthesiologists. We hypothesised that coffee consumption was positively correlated with work satisfaction. METHODS: We invited anaesthesiologists attending the 34th congress of The Scandinavian Society of Anaesthesiology and Intensive Care Medicine in Malmö, Sweden, September 2017 to participate in a paper-based survey. We collected data on characteristics of the respondents, coffee drinking and work satisfaction, and compared coffee vs non-coffee drinkers with regard to work satisfaction scored on a modified Wong-Baker Faces Pain Rating Scale (Visual Analogue Scale from 0 to 10). RESULTS: A total of 271 anaesthesiologists participated in the survey, of which 265 (97.7%) of the questionnaires contained valid data. Some 143 (54.0%) of the respondents were women, the median (interquartile range, IQR) age was 41.0 (35.0-49.5) years, and 242 (91.3%) were coffee drinkers. Coffee drinkers consumed median 4.0 (IQR: 2.5-5.0) cups of coffee daily. Overall work satisfaction was median 8 (IQR: 8-9), with no difference between respondents drinking coffee and those who did not (median 8 (IQR: 8-9) vs 8 (IQR: 8-9), Wilcoxon rank sum test, P = 0.62). Also, we found no association between work satisfaction and the number of cups of coffee consumed daily (r2  = 0.005, P = 0.24). CONCLUSION: In this survey, we found high work satisfaction among Scandinavian anaesthesiologists, with no difference between coffee and non-coffee drinkers.

The effect on glycaemic control of low-volume high-intensity interval training versus endurance training in individuals with type 2 diabetes.

AIM: To evaluate whether high-intensity interval training (HIIT) with a lower time commitment can be as effective as endurance training (END) on glycaemic control, physical fitness and body composition in individuals with type 2 diabetes. MATERIALS AND METHODS: A total of 29 individuals with type 2 diabetes were allocated to control (CON; no training), END or HIIT groups. Training groups received 3 training sessions per week consisting of either 40 minutes of cycling at 50% of peak workload (END) or 10 1-minute intervals at 95% of peak workload interspersed with 1 minute of active recovery (HIIT). Glycaemic control (HbA1c, oral glucose tolerance test, 3-hour mixed meal tolerance test with double tracer technique and continuous glucose monitoring [CGM]), lipolysis, VO2 peak and body composition were evaluated before and after 11 weeks of intervention. RESULTS: Exercise training increased VO2 peak more in the HIIT group (20% ± 20%) compared with the END group (8% ± 9%) despite lower total energy expenditure and time usage during the training sessions. HIIT decreased whole body and android fat mass compared with the CON group. In addition, visceral fat mass, HbA1c, fasting glucose, postprandial glucose, glycaemic variability and HOMA-IR decreased after HIIT. The reduced postprandial glucose in the HIIT group was driven primarily by a lower rate of exogenous glucose appearance. In the CON group, postprandial lipolysis was augmented over the 11-week control period. CONCLUSIONS: Despite a ~45% lower training volume, HIIT resulted in similar or even better improvements in physical fitness, body composition and glycemic control compared to END. HIIT therefore appears to be an important time-efficient treatment for individuals with type 2 diabetes.

Effect of 6 wk of high-intensity one-legged cycling on functional sympatholysis and ATP signaling in patients with heart failure.

Breathlessness during daily activities is the primary symptom in patients with heart failure (HF). Poor correlation between the hemodynamic parameters of left ventricular performance and perceived symptoms suggests that other factors, such as skeletal muscle function, play a role in determining exercise capacity. We investigated the effect of 6 wk of high-intensity, one-legged cycling (HIC; 8 × 4 at 90% one-legged cycling max) on 1) the ability to override sympathetic vasoconstriction (arterial infusion of tyramine) during one-legged knee-extensor exercise (KEE), 2) vascular function (arterial infusion of ACh, sodium nitroprusside, tyramine, and ATP), and 3) exercise capacity in HF patients with reduced ejection fraction ( n = 8) compared with healthy individuals ( n = 6). Arterial tyramine infusion lowered leg blood flow and leg vascular conductance at rest and during KEE before the training intervention in both groups ( P < 0.05) but not during KEE after the training intervention. There was no difference between groups. The peak vasodilatory response to ATP was blunted in HF patients ( P < 0.05), whereas there was no difference in ACh- and sodium nitroprusside-induced vasodilation between HF patients and healthy individuals. ACh-induced vasodilation increased in HF patients after the training intervention ( P < 0.05). HIC improved aerobic capacity in both groups ( P < 0.05), whereas only HF patients made improvements in the 6-min walking distance ( P < 0.05). These results suggest that exercise hyperemia and functional sympatholysis are not altered in HF patients and that functional sympatholysis is improved with HIC in both HF patients and healthy individuals. Moreover, these results suggest that the peak vasodilatory response to ATP is blunted in HF. NEW & NOTEWORTHY The ability to override sympathetic vasoconstrictor activity (by arterial tyramine infusion) during exercise is not different between heart failure patients and healthy individuals and is improved by high-intensity, one-legged cycling training. The peak vasodilatory response to ATP is reduced in heart failure patients.