Enjeux de santé mentale et consommation de substances psychoactives en contexte sexuel ou «chemsex» chez les HARSAH à Montréal

Contexte : Les hommes ayant des relations sexuelles avec des hommes (HARSAH) sont plus à risque de présenter des symptômes de dépression et d’anxiété comparativement à leurs pairs hétérosexuels. Le chemsex est une pratique qui consiste en la consommation de gamma-hydroxybutyrate, méthamphétamine, cocaïne, ecstasy et/ou kétamine dans un contexte sexuel. Peu de données probantes existent concernant l’association de cette pratique avec la présence de symptômes d’anxiété et de dépression, et si cette relation est modérée par le statut VIH. Méthode : 1179 HARSAH ont été recrutés lors de la première vague montréalaise de la cohorte ENGAGE par la méthode d’échantillonnage par les répondants (RDS). La présence de symptômes d’anxiété et de dépression a été définie par un score ≥ 8 à chacune des sous échelles d’anxiété et de dépression de l’échelle « Hospital Anxiety and Depression Scale ». L’association de la pratique du chemsex avec la présence de symptômes d’anxiété et de dépression a été mesurée via deux modèles de régression logistiques multivariées. L’interaction statistique du statut VIH autorapporté dans la relation entre la pratique du chemsex et les symptômes d’anxiété et de dépression a été testée en ajustant par les facteurs de confusion potentiels. Les rapports de côtes ajustés (ORa) et d’intervalles de confiance à 95% (IC95%) sont présentés. Les analyses sont ajustées selon le poids RDS des participants. Résultats : Les symptômes d’anxiété ont été positivement associés avec la pratique du chemsex chez les individus séronégatifs en comparaison aux individus séronégatifs qui ne pratiquent pas le chemsex (aOR=1.75, IC95% : 1.14-2.68). Les facteurs de confusion significatifs comprennent : avoir un plus jeune âge (aOR=1.04, IC95% : 1.02-1.05) ; un niveau d’éducation ≤ CEGEP ou Technique (aOR=1.89, IC95% : 1.28-2.82) ; l’abus d’alcool (aOR=1.45, IC95% : 1.08-1.96) ; un historique d’abus sexuel au cours de la vie (aOR=3.47, IC95% : 2.46-4.92) et être positif à une infection gonococcique, à C. trachomatis ou à la syphilis (aOR=0.45, IC95% : 0.27-0.75). Les symptômes de dépression ont été positivement associés à la pratique du chemsex chez les individus séronégatifs en comparaison aux individus séronégatifs qui ne pratiquent pas le chemsex (aOR=1.66, IC95% : 1.11-2.46). Les facteurs de confusion significatifs comprennent : ne pas s’identifier comme un homme cisgenre (aOR=2.77, IC95% : 1.78-4.28) et un historique d’abus sexuel au cours de la vie (aOR=2.85, IC95% : 2.08-3.91). Conclusion : Les résultats suggèrent que la pratique du chemsex est associée à la présence de symptômes d’anxiété et de dépression chez les individus séronégatifs mais pas chez les individus séropositifs. Des analyses longitudinales permettront d’identifier la direction de ces associations. L’implication des résultats pour le développement d’interventions est discutée.Background: Gay, bisexual and other men who have sex with men (GBM) are at higher risk of anxiety and/or depression symptoms compared to the general population. Chemsex is defined as the use of gamma-Hydroxybutyric acid, methamphetamine, cocaine, ecstasy and ketamine during sex. Little is known regarding the association between chemsex and anxiety and depression symptoms, and if this relation is moderated by HIV status. Methods: Montréal baseline data from the Engage cohort study were used. 1179 sexually active GBM ≥ 16 years old were recruited via respondent-driven sampling (RDS). Presence of anxiety and depression symptoms were defined using a score of ≥ 8 on either the anxiety- or depression-subscale of the Hospital Anxiety and Depression Scale. Using two logistic multivariate models, we assessed the association of chemsex with symptoms of anxiety and depression. Statistical interaction between self-reported HIV status and chemsex were tested in each multivariate model adjusting for potential confounders. Adjusted odds ratios (aOR) and 95% confidence intervals (95%CI) are reported; analyses were RDS-adjusted. Results: Effect modification by self-reported HIV status was statistically significant for anxiety and depression symptoms. Anxiety symptoms were positively associated with HIV-negative GBM engaging in chemsex compared to HIV-negative GBM not engaging in chemsex (aOR=1.75, 95%CI:1.14-2.68); significant confounders included being younger (aOR=1.04, 95%CI:1.02-1.05), education ≤ high school diploma (aOR=1.89, 95%CI:1.28-2.82), alcohol misuse (aOR=1.45, 95%CI:1.08-1.96), lifetime history of sexual abuse (aOR=3.47, 95%CI:2.46-4.92) and being positive to C. trachomatis, gonococcal or syphilis infection (aOR=0.45, 95%CI:0.27-0.75). Depression symptoms were positively associated with HIV-negative GBM engaging in chemsex compared to HIV-negative GBM not engaging in chemsex (aOR=1.66, 95%CI:1.11-2.46); significant confounders included not identifying as a cis-gendered male (aOR=2.77, 95%CI:1.78-4.28) and lifetime history of sexual abuse (aOR=2.85, 95%CI:2.08-3.91). Conclusions: Results suggest that engaging in chemsex is linked to anxiety and depression symptoms among HIV-negative GBM but not for GBM living with HIV. Longitudinal research is needed to understand the directionality of identified associations. Implications of results for intervention strategies are discussed

Human MCTS1-dependent translation of JAK2 is essential for IFN-γ immunity to mycobacteria.

Human inherited disorders of interferon-gamma (IFN-γ) immunity underlie severe mycobacterial diseases. We report X-linked recessive MCTS1 deficiency in men with mycobacterial disease from kindreds of different ancestries (from China, Finland, Iran, and Saudi Arabia). Complete deficiency of this translation re-initiation factor impairs the translation of a subset of proteins, including the kinase JAK2 in all cell types tested, including T lymphocytes and phagocytes. JAK2 expression is sufficiently low to impair cellular responses to interleukin-23 (IL-23) and partially IL-12, but not other JAK2-dependent cytokines. Defective responses to IL-23 preferentially impair the production of IFN-γ by innate-like adaptive mucosal-associated invariant T cells (MAIT) and γδ T lymphocytes upon mycobacterial challenge. Surprisingly, the lack of MCTS1-dependent translation re-initiation and ribosome recycling seems to be otherwise physiologically redundant in these patients. These findings suggest that X-linked recessive human MCTS1 deficiency underlies isolated mycobacterial disease by impairing JAK2 translation in innate-like adaptive T lymphocytes, thereby impairing the IL-23-dependent induction of IFN-γ

Suicide attempt with self-made <i>Taxus baccata</i> leaf capsules: survival following the application of extracorporeal membrane oxygenation for ventricular arrythmia and refractory cardiogenic shock

<p><b>Context:</b> Yew intoxication has been known for many years; high dose ingestion of <i>Taxus baccata</i> leads to cardiac toxicity mediated by calcium and sodium channel blocking properties. We present a case report of a patient who attempted suicide after <i>T. baccata</i> ingestion, causing refractory cardiogenic shock requiring temporary circulatory assistance by veno-arterial extra corporeal membrane oxygenation (VA ECMO).</p> <p><b>Case details:</b> A 28-year-old man was admitted to the critical care unit of a university hospital for arrhythmia after ingestion of self-made <i>T. baccata</i> leaf capsules. He rapidly developed cardiovascular collapse requiring mechanical ventilation, high dose intravenous catecholamines and electrical cardioversion. A femoro-femoral VA ECMO was implanted due to severe biventricular dysfunction and ventricular arrhythmia, associated with continuous renal replacement therapy. Taxol A, taxol B and baccatin III were detected and measured in both blood and urine samples by high-performance liquid chromatography tandem mass spectrometry, and kinetics suggested urinary excretion. Two days after hospital admission, VA ECMO and continuous renal replacement therapy were removed with full recovery of cardiac function.</p> <p><b>Discussion:</b> Our experience suggests that circulatory assistance by VA ECMO and continuous renal replacement therapy seem to be effective safe second-line therapeutic options in critically ill cases of severe yew intoxication with refractory cardiogenic shock due to arrhythmia.</p

Neurally adjusted ventilatory assist (NAVA) versus pressure support ventilation: patient-ventilator interaction during invasive ventilation delivered by tracheostomy

Abstract Background Prolonged weaning is a major issue in intensive care patients and tracheostomy is one of the last resort options. Optimized patient-ventilator interaction is essential to weaning. The purpose of this study was to compare patient-ventilator synchrony between pressure support ventilation (PSV) and neurally adjusted ventilatory assist (NAVA) in a selected population of tracheostomised patients. Methods We performed a prospective, sequential, non-randomized and single-centre study. Two recording periods of 60 min of airway pressure, flow, and electrical activity of the diaphragm during PSV and NAVA were recorded in a random assignment and eight periods of 1 min were analysed for each mode. We searched for macro-asynchronies (ineffective, double, and auto-triggering) and micro-asynchronies (inspiratory trigger delay, premature, and late cycling). The number and type of asynchrony events per minute and asynchrony index (AI) were determined. The two respiratory phases were compared using the non-parametric Wilcoxon test after testing the equality of the two variances (F-Test). Results Among the 61 patients analysed, the total AI was lower in NAVA than in PSV mode: 2.1% vs 14% (p < 0.0001). This was mainly due to a decrease in the micro-asynchronies index: 0.35% vs 9.8% (p < 0.0001). The occurrence of macro-asynchronies was similar in both ventilator modes except for double triggering, which increased in NAVA. The tidal volume (ml/kg) was lower in NAVA than in PSV (5.8 vs 6.2, p < 0.001), and the respiratory rate was higher in NAVA than in PSV (28 vs 26, p < 0.05). Conclusion NAVA appears to be a promising ventilator mode in tracheotomised patients, especially for those requiring prolonged weaning due to the decrease in asynchronies

Neutralizing IFN-γ autoantibodies are rare and pathogenic in HLA-DRB1*15:02 or 16:02 individuals.

BACKGROUNDWeakly virulent environmental mycobacteria (EM) can cause severe disease in HLA-DRB1*15:02 or 16:02 adults harboring neutralizing anti-IFN-γ autoantibodies (nAIGAs). The overall prevalence of nAIGAs in the general population is unknown, as are the penetrance of nAIGAs in HLA-DRB1*15:02 or 16:02 individuals and the proportion of patients with unexplained, adult-onset EM infections carrying nAIGAs.METHODSThis study analyzed the detection and neutralization of anti-IFN-γ autoantibodies (auto-Abs) from 8,430 healthy individuals of the general population, 257 HLA-DRB1*15:02 or 16:02 carriers, 1,063 patients with autoimmune disease, and 497 patients with unexplained severe disease due to EM.RESULTSWe found that anti-IFN-γ auto-Abs detected in 4,148 of 8,430 healthy individuals (49.2%) from the general population of an unknown HLA-DRB1 genotype were not neutralizing. Moreover, we did not find nAIGAs in 257 individuals carrying HLA-DRB1* 15:02 or 16:02. Additionally, nAIGAs were absent in 1,063 patients with an autoimmune disease. Finally, 7 of 497 patients (1.4%) with unexplained severe disease due to EM harbored nAIGAs.CONCLUSIONThese findings suggest that nAIGAs are isolated and that their penetrance in HLA-DRB1*15:02 or 16:02 individuals is low, implying that they may be triggered by rare germline or somatic variants. In contrast, the risk of mycobacterial disease in patients with nAIGAs is high, confirming that these nAIGAs are the cause of EM disease.FUNDINGThe Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI095983 and U19AIN1625568), the National Center for Advancing Translational Sciences (NCATS), the NIH Clinical and Translational Science Award (CTSA) program (UL1 TR001866), the French National Research Agency (ANR) under the Investments for the Future program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), ANR-GENMSMD (ANR-16-CE17-0005-01), ANR-MAFMACRO (ANR-22-CE92-0008), ANRSECTZ170784, the French Foundation for Medical Research (FRM) (EQU201903007798), the ANRS-COV05, ANR GENVIR (ANR-20-CE93-003), and ANR AI2D (ANR-22-CE15-0046) projects, the ANR-RHU program (ANR-21-RHUS-08-COVIFERON), the European Unions Horizon 2020 research and innovation program under grant agreement no. 824110 (EASI-genomics), the Square Foundation, Grandir - Fonds de solidarité pour lenfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, the Battersea &amp; Bowery Advisory Group, William E. Ford, General Atlantics Chairman and Chief Executive Officer, Gabriel Caillaux, General Atlantics Co-President, Managing Director, and Head of business in EMEA, and the General Atlantic Foundation, Institut National de la Santé et de la Recherche Médicale (INSERM) and of Paris Cité University. JR was supported by the INSERM PhD program for doctors of pharmacy (poste daccueil INSERM). JR and TLV were supported by the Bettencourt-Schueller Foundation and the MD-PhD program of the Imagine Institute. MO was supported by the David Rockefeller Graduate Program, the Funai Foundation for Information Technology (FFIT), the Honjo International Scholarship Foundation (HISF), and the New York Hideyo Noguchi Memorial Society (HNMS)