The impact of job-demand-control-support on leptin and ghrelin as biomarkers of stress in emergency healthcare workers

Despite the available literature on the consequences of night shiftwork on stress and food intake, its impact on leptin and ghrelin has never been studied. We previously demonstrated that leptin and ghrelin were biomarkers related to stress, and acute stress-induced a decrease in leptin levels and an increase in ghrelin levels. We performed a prospective observational study to assess the influence of night work, nutrition, and stress on the levels of ghrelin and leptin among emergency healthcare workers (HCWs). We took salivary samples at the beginning of a day shift and/or at the end of a night shift. We also monitored stress using the job demand-control-support model of Karasek. We recorded 24-h food intake during the day shift and the consecutive night shift and during night work and the day before. We included 161 emergency HCWs. Emergency HCWs had a tendency for decreased levels of leptin following the night shift compared to before the dayshift (p = 0.067). Furthermore, the main factors explaining the decrease in leptin levels were an increase in job-demand (coefficient −54.1, 95 CI −99.0 to −0.92) and a decrease in job control (−24.9, −49.5 to −0.29). Despite no significant changes in ghrelin levels between shifts, social support was the main factor explaining the increase in ghrelin (6.12, 0.74 to 11.5). Food intake (kcal) also had a negative impact on leptin levels, in addition to age. Ghrelin levels also decreased with body mass index, while age had the opposite effect. In conclusion, we confirmed that ghrelin and leptin as biomarkers of stress were directly linked to the job demand-control-support model of Karasek, when the main cofounders were considered

Arrhythmic risk prediction in arrhythmogenic right ventricular cardiomyopathy: external validation of the arrhythmogenic right ventricular cardiomyopathy risk calculator

Aims Arrhythmogenic right ventricular cardiomyopathy (ARVC) causes ventricular arrhythmias (VAs) and sudden cardiac death (SCD). In 2019, a risk prediction model that estimates the 5-year risk of incident VAs in ARVC was developed (ARVCrisk.com). This study aimed to externally validate this prediction model in a large international multicentre cohort and to compare its performance with the risk factor approach recommended for implantable cardioverter-defibrillator (ICD) use by published guidelines and expert consensus.Methods and results In a retrospective cohort of 429 individuals from 29 centres in North America and Europe, 103 (24%) experienced sustained VA during a median follow-up of 5.02 (2.05-7.90) years following diagnosis of ARVC. External validation yielded good discrimination [C-index of 0.70 (95% confidence interval-CI 0.65-0.75)] and calibration slope of 1.01 (95% CI 0.99-1.03). Compared with the three published consensus-based decision algorithms for ICD use in ARVC (Heart Rhythm Society consensus on arrhythmogenic cardiomyopathy, International Task Force consensus statement on the treatment of ARVC, and American Heart Association guidelines for VA and SCD), the risk calculator performed better with a superior net clinical benefit below risk threshold of 35%.Conclusion Using a large independent cohort of patients, this study shows that the ARVC risk model provides good prognostic information and outperforms other published decision algorithms for ICD use. These findings support the use of the model to facilitate shared decision making regarding ICD implantation in the primary prevention of SCD in ARVC

Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility

Brugada syndrome (BrS) is a cardiac arrhythmia disorder associated with sudden death in young adults. With the exception of SCN5A, encoding the cardiac sodium channel NaV1.5, susceptibility genes remain largely unknown. Here we performed a genome-wide association meta-analysis comprising 2,820 unrelated cases with BrS and 10,001 controls, and identified 21 association signals at 12 loci (10 new). Single nucleotide polymorphism (SNP)-heritability estimates indicate a strong polygenic influence. Polygenic risk score analyses based on the 21 susceptibility variants demonstrate varying cumulative contribution of common risk alleles among different patient subgroups, as well as genetic associations with cardiac electrical traits and disorders in the general population. The predominance of cardiac transcription factor loci indicates that transcriptional regulation is a key feature of BrS pathogenesis. Furthermore, functional studies conducted on MAPRE2, encoding the microtubule plus-end binding protein EB2, point to microtubule-related trafficking effects on NaV1.5 expression as a new underlying molecular mechanism. Taken together, these findings broaden our understanding of the genetic architecture of BrS and provide new insights into its molecular underpinnings

Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility.

Brugada syndrome (BrS) is a cardiac arrhythmia disorder associated with sudden death in young adults. With the exception of SCN5A, encoding the cardiac sodium channel Na1.5, susceptibility genes remain largely unknown. Here we performed a genome-wide association meta-analysis comprising 2,820 unrelated cases with BrS and 10,001 controls, and identified 21 association signals at 12 loci (10 new). Single nucleotide polymorphism (SNP)-heritability estimates indicate a strong polygenic influence. Polygenic risk score analyses based on the 21 susceptibility variants demonstrate varying cumulative contribution of common risk alleles among different patient subgroups, as well as genetic associations with cardiac electrical traits and disorders in the general population. The predominance of cardiac transcription factor loci indicates that transcriptional regulation is a key feature of BrS pathogenesis. Furthermore, functional studies conducted on MAPRE2, encoding the microtubule plus-end binding protein EB2, point to microtubule-related trafficking effects on Na1.5 expression as a new underlying molecular mechanism. Taken together, these findings broaden our understanding of the genetic architecture of BrS and provide new insights into its molecular underpinnings

Leptin as a Biomarker of Stress: A Systematic Review and Meta-Analysis

International audienceBackground: Leptin is a satiety hormone mainly produced by white adipose tissue. Decreasing levels have been described following acute stress. Objective: To conduct a systematic review and meta-analysis to determine if leptin can be a biomarker of stress, with levels decreasing following acute stress. Methods: PubMed, Cochrane Library, Embase, and ScienceDirect were searched to obtain all articles studying leptin levels after acute stress on 15 February 2021. We included articles reporting leptin levels before and after acute stress (physical or psychological) and conducted random effects meta-analysis (DerSimonian and Laird approach). We conducted Meta-regressions and sensitivity analyses after exclusion of groups outside the metafunnel. Results: We included seven articles—four cohort and three case-control studies—(28 groups) from 27,983 putative articles. Leptin levels decreased after the stress intervention (effect size = −0.34, 95%CI −0.66 to −0.02) compared with baseline levels, with a greater decrease after 60 min compared to mean decrease (−0.45, −0.89 to −0.01) and in normal weight compared to overweight individuals (−0.79, −1.38 to −0.21). There was no difference in the overweight population. Sensitivity analyses demonstrated similar results. Levels of leptin after stress decreased with sex ratio—i.e., number of men/women—(−0.924, 95%CI −1.58 to −0.27) and increased with the baseline levels of leptin (0.039, 0.01 to 0.07). Conclusions: Leptin is a biomarker of stress, with a decrease following acute stress. Normal-weight individuals and women also have a higher variation of leptin levels after stress, suggesting that leptin may have implications in obesity development in response to stress in a sex-dependent manner

Creatine supplementation and VO 2 max: a systematic review and meta-analysis

International audienceAlthough creatine supplementation is well-known to increase exercise performance in acute high-intensity exercises, its role in aerobic performance based on VO2max is more controversial. Thus, we performed a systematic review and meta-analysis on the effects of creatine supplementation on VO2max. PubMed, Cochrane, Embase, and ScienceDirect were searched for randomized controlled trials (RCTs) reporting VO2max in creatine supplementation and placebo groups before and after supplementation. We computed a random-effects meta-analysis on VO2max at baseline, within groups following supplementation, on changes on VO2max between groups, and after supplementation between groups. Sensitivity analyses and meta-regression were conducted. We included 19 RCTs for a total of 424 individuals (mean age 30 years old, 82% men). VO2max did not differ at baseline between groups (creatine and placebo). Participants in both groups were engaged in exercise interventions in most studies (80%). Using changes in VO2max, VO2max increased in both groups but increased less after creatine supplementation than placebo (effect size [ES] = −0.32, 95%CI = −0.51 to −0.12, p = 0.002). Comparisons after creatine supplementation confirmed a lower VO2max in the creatine group compared to the placebo group (ES= −0.20, 95%CI = −0.39 to −0.001, p = 0.049). Meta-analysis after exclusion from meta-funnel resulted in similar outcomes in a subgroup of young and healthy participants. Meta-regressions on characteristics of supplementation, physical training, or sociodemographic were not statistically significant. Creatine supplementation has a negative effect on VO2max, regardless of the characteristics of training, supplementation, or population characteristics

Predictive performance of blood S100B in the management of patients over 65 years old with mild traumatic brain injury

International audienceBackground: We previously assessed the inclusion of S100B blood determination into clinical decision rules for mild traumatic brain injury (mTBI) management in the Emergency Department (ED) of Clermont-Ferrand Hospital. At the 0.10 µg/L threshold, S100B reduced the use of cranial computed tomography (CCT) scan in adults by at least 30% with a ~100% sensitivity. Older patients had higher serum S100B values, resulting in lower specificity (18.7%) and decreased CCT reduction. We conducted this study to confirm the age effect on S100B concentrations, and to propose new decisional thresholds for older patients. Methods: A total of 1172 mTBI patients aged 65 and over were included. They were divided into three age-groups: 65-79, 80-89, and ≥ 90 years old. S100B's performance to identify intracranial lesions (sensitivity (SE) and specificity (SP)) was assessed using the routine 0.10 µg/L threshold and also other more efficient thresholds established for each age group. Results: S100B concentration medians were 0.18 µg/L, 0.26 µg/L, and 0.32 µg/L for the 65-79, 80-89, and ≥ 90 years old age-groups, respectively (p < 0.001). The most efficient thresholds were 0.11 µg/L for the 65-79 age-group and 0.15 µg/L for the other groups. At these new thresholds, SP was respectively 28.4%, 34.3%, and 20.5% for each age-group vs. 24.9%, 18.2%, and 10.5% at the 0.10 µg/L threshold. Conclusions: Adjustment of the S100B threshold is necessary in older patients' management. An increased threshold of 0.15 µg/L is particularly interesting for patients ≥ 80 years old, allowing a significant increase of CCT scan reduction (29.3%)

Impact of 24 h shifts on urinary catecholamine in emergency physicians: a cross-over randomized trial

International audienceAbstract 24-h shift (24 hS) exposed emergency physicians to a higher stress level than 14-h night shift (14 hS), with an impact spreading on several days. Catecholamines are supposed to be chronic stress biomarker. However, no study has used catecholamines to assess short-term residual stress or measured them over multiple shifts. A shift-randomized trial was conducted to study urinary catecholamines levels of 17 emergency physicians during a control day (clerical work on return from leave) and two working day (14 hS and 24 hS). The Wilcoxon matched-pairs test was utilized to compare the mean catecholamine levels. Additionally, a multivariable generalized estimating equations model was employed to further analyze the independent relationships between key factors such as shifts (compared to control day), perceived stress, and age with catecholamine levels. Dopamine levels were lower during 24 hS than 14 hS and the control day. Norepinephrine levels increased two-fold during both night shifts. Epinephrine levels were higher during the day period of both shifts than on the control day. Despite having a rest day, the dopamine levels did not return to their normal values by the end of the third day after the 24 hS. The generalized estimating equations model confirmed relationships of catecholamines with workload and fatigue. To conclude, urinary catecholamine biomarkers are a convenient and non-invasive strong measure of stress during night shifts, both acutely and over time. Dopamine levels are the strongest biomarker with a prolonged alteration of its circadian rhythm. Due to the relation between increased catecholamine levels and both adverse psychological effects and cardiovascular disease, we suggest that emergency physicians restrict their exposure to 24 hS to mitigate these risks

Ionized Magnesium: Interpretation and Interest in Atrial Fibrillation

Background: Magnesium (Mg) is often used to manage de novo atrial fibrillation (AF) in the emergency department (ED) and intensive care unit (ICU). Point of care measurement of ionized magnesium (iMg) allows a rapid identification of patients with impaired magnesium status, however, unlike ionized calcium, the interpretation of iMg is not entirely understood. Thus, we evaluated iMg reference values, correlation between iMg and plasmatic magnesium (pMg), and the impact of pH and albumin variations on iMg levels. Secondary objectives were to assess the incidence of hypomagnesemia in de novo AF. Methods: A total of 236 emergency department and intensive care unit patients with de novo AF, and 198 control patients were included. Reference values were determined in the control population. Correlation and concordance between iMg and pMg were studied using calcium (ionized and plasmatic) as a control in the whole study population. The impact of albumin and pH was assessed in the discordant iMg and pMg values. Lastly, we assessed the incidence of ionized hypomagnesemia (hypoMg) among de novo AF. Results: The reference range values established in our study for iMg were: 0.48–0.65 mmol/L (the manufacturers were: 0.45–0.60 mmol/L). A strong correlation was observed between pMg and iMg (r = 0.85), but, unlike for calcium values, there was no significant impact of pH and albumin in iMg/pMg interpretation. The incidence of hypoMg among de novo AF patients was 8.5% (12.7% using our ranges). When using our ranges, we found a significant link (p = 0.01) between hyopMg and hypokalemia. Conclusion: We highlight the need for more accurate reference range values of iMg. Furthermore, our results suggest that blood Mg content is not identical to that of calcium. The incidence of ionized hypomagnesemia among de novo AF patients in our study is 8.5%

Burden of rare variants in arrhythmogenic cardiomyopathy with right dominant form associated genes provides new insights for molecular diagnosis and clinical management.

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