Respective roles of social deprivation, health literacy, and clinical factors for COVID-19: a case-control study in hospitalized patients

IntroductionTo investigate the association between social deprivation and COVID-19 among hospitalized patients in an underprivileged department of the greater Paris area.MethodsIndividuals hospitalized for COVID-19 between March 1st and October 31, 2020, were included, matched on age and sex, and compared with patients hospitalized for any other reason with negative RT-PCR for SARS-CoV-2, through a case-control study. Clinical, socio-demographic characteristics, health literacy, and social deprivation, assessed by the EPICES score, were collected. Factors associated with COVID-19 in hospitalized patients were assessed using univariate and multivariate logistic regression models.Results69 cases and 180 controls were included. Participants were mostly men (N = 148: 59.4%) aged 65 or older (N = 109: 44.1%). Median EPICES score was 43.2 (IQR 29.4–62.9). EPICES score > 30.17 (precariousness threshold) was not significantly associated with COVID-19 in hospitalized patients (adjusted odds ratio (aOR) = 0.46; 95% Confidence Interval (CI) [0.21–1.01]). Advanced age, higher BMI, professional activity, home area of less than 25 m2 per person, and low health literacy, were significantly associated with COVID-19 in hospitalized patients.DiscussionThis study highlights probable risk factors for specific exposition in disadvantaged area: maintenance of professional activity, smaller home area, and low health literacy

Serelaxin as a potential treatment for renal dysfunction in cirrhosis: Preclinical evaluation and results of a randomized phase 2 trial

<div><p>Background</p><p>Chronic liver scarring from any cause leads to cirrhosis, portal hypertension, and a progressive decline in renal blood flow and renal function. Extreme renal vasoconstriction characterizes hepatorenal syndrome, a functional and potentially reversible form of acute kidney injury in patients with advanced cirrhosis, but current therapy with systemic vasoconstrictors is ineffective in a substantial proportion of patients and is limited by ischemic adverse events. Serelaxin (recombinant human relaxin-2) is a peptide molecule with anti-fibrotic and vasoprotective properties that binds to relaxin family peptide receptor-1 (RXFP1) and has been shown to increase renal perfusion in healthy human volunteers. We hypothesized that serelaxin could ameliorate renal vasoconstriction and renal dysfunction in patients with cirrhosis and portal hypertension.</p><p>Methods and findings</p><p>To establish preclinical proof of concept, we developed two independent rat models of cirrhosis that were characterized by progressive reduction in renal blood flow and glomerular filtration rate and showed evidence of renal endothelial dysfunction. We then set out to further explore and validate our hypothesis in a phase 2 randomized open-label parallel-group study in male and female patients with alcohol-related cirrhosis and portal hypertension. Forty patients were randomized 1:1 to treatment with serelaxin intravenous (i.v.) infusion (for 60 min at 80 μg/kg/d and then 60 min at 30 μg/kg/d) or terlipressin (single 2-mg i.v. bolus), and the regional hemodynamic effects were quantified by phase contrast magnetic resonance angiography at baseline and after 120 min. The primary endpoint was the change from baseline in total renal artery blood flow.</p><p>Therapeutic targeting of renal vasoconstriction with serelaxin in the rat models increased kidney perfusion, oxygenation, and function through reduction in renal vascular resistance, reversal of endothelial dysfunction, and increased activation of the AKT/eNOS/NO signaling pathway in the kidney. In the randomized clinical study, infusion of serelaxin for 120 min increased total renal arterial blood flow by 65% (95% CI 40%, 95%; <i>p <</i> 0.001) from baseline. Administration of serelaxin was safe and well tolerated, with no detrimental effect on systemic blood pressure or hepatic perfusion. The clinical study’s main limitations were the relatively small sample size and stable, well-compensated population.</p><p>Conclusions</p><p>Our mechanistic findings in rat models and exploratory study in human cirrhosis suggest the therapeutic potential of selective renal vasodilation using serelaxin as a new treatment for renal dysfunction in cirrhosis, although further validation in patients with more advanced cirrhosis and renal dysfunction is required.</p><p>Trial registration</p><p>ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT01640964" target="_blank">NCT01640964</a></p></div

The articulation of racism and homophobia in contemporary France

Fondée sur l'ethnographie d'associations parisiennes gays noires et sur des entretiens semi-biographiques auprès de personnes se définissant comme gay noir, cette thèse a pour objet l'articulation du racisme et de l'homophobie en contexte français contemporain. La construction sociale de ces oppressions comme séparées et hiérarchisées alimente un processus global de racisation de l'homophobie qui pose les minorités raciales comme supposément plus homophobes. Les personnes interrogées – tant individuellement que collectivement – ont tendance à être plus préoccupées par l'homophobie que par le racisme et à comprendre leur marginalisation comme l'effet d'une « homophobie noire » exacerbée, faits qui participent à alimenter la racisation de l'homophobie. Pour expliquer la subordination individuelle et collective du racisme a l'homophobie, l'analyse porte dans un premier temps sur la façon dont racisme et homophobie s'articulent et se coconstruisent comme instances de marginalisation dans la vie quotidienne des gays noirs. Elle interroge l'effet de la marginalisation sexuelle sur la marginalisation raciale et inversement en espace majoritaire et au sein des groupes statutaires d'appartenance des gays noirs. Elle porte ensuite sur la construction de soi en tant que gay noir et sur l'émergence et la structuration de mobilisations associatives gays noires. D'un point de vue théorique, cette thèse se situe au sein du paradigme intersectionnel et propose des éléments méthodologiques, analytiques et théoriques visant à rendre opératoire l'intersectionnalité dans une démarche de recherche empiriquement fondée. Elle propose, en outre, des éléments portant sur la distinction analytique entre race et ethnicité et avance des propositions conceptuelles pour appréhender la race en tant que rapport social.Based on an ethnography of Parisian black gay organizations and semi-biographic interviews of self-identified black gay individuals, this Ph.D dissertation focuses on the articulation of racism and homophobia in contemporary France. Racism and homophobia are socially constructed as separate and hierarchized, supporting the “racialization of homophobia” (a process that labels racial minorities as particularly homophobic). Interviewees tend to be more preoccupied by homophobia than racism, both individually and collectively, and tend to understand their marginalization as the result of an exacerbated “black homophobia”. These facts fuel the aforementioned racialization of homophobia. To explain this deprioritization of racism vis-à-vis homophobia, this analysis focuses on the articulation and the co-construction of racism and homophobia as marginalization factors in black gay individuals’ daily lives. The effects of sexual marginalization on racial marginalization and vice versa are studied in various contexts (within homosexual spaces, black spaces and majority society). Then, the analysis concentrates on the process of self-construction as a black gay individual and on the emergence and structuring of black gay organizations. On a theoretical level, this intersectional research suggests methodological, analytical and theoretical elements to implement intersectionality in empirically grounded studies. Additionally, it proposes elements to analytically distinguish race and ethnicity and to conceptualize race as a structural power relationship

NEPHROPATHY IN THE COURSE OF HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION - A CLINICOPATHOLOGICAL STUDY

We report 16 patients with HIV1 infection with biopsy-proven renal involvement. Nine patients were caucasians and seven were blacks. There were 11 patients at stage II and 5 at stage IV of the HIV1 infection. Three patterns of histologic lesions were found: 6 patients, all blacks, with nephrotic syndrome and/or renal insufficiency had focal and segmental glomerulosclerosis (FSGS) with tubulo-interstitial lesions. In contrast, 6 patients, all caucasians, had various types of glomerulonephritis characterized by immunoglobulin and complement deposits; 3 of them were membranoproliferative glomerulonephritis (MPGN). The four remaining patients had predominant tubulo-interstitial lesions. In three patients who had FSGS, treatment by AZT induced temporary improvement of renal function and hemodialysis could be interrupted for a few months. The cure of infectious foci was followed by improvement in renal signs in two out of the 3 MPGN patients

Systemic inflammation in decompensated cirrhosis: Characterization and role in acute-on-chronic liver failure.

Acute-on-chronic liver failure (ACLF) in cirrhosis is characterized by acute decompensation (AD), organ failure(s), and high short-term mortality. Recently, we have proposed (systemic inflammation [SI] hypothesis) that ACLF is the expression of an acute exacerbation of the SI already present in decompensated cirrhosis. This study was aimed at testing this hypothesis and included 522 patients with decompensated cirrhosis (237 with ACLF) and 40 healthy subjects. SI was assessed by measuring 29 cytokines and the redox state of circulating albumin (HNA2), a marker of systemic oxidative stress. Systemic circulatory dysfunction (SCD) was estimated by plasma renin (PRC) and copeptin (PCC) concentrations. Measurements were performed at enrollment (baseline) in all patients and sequentially during hospitalization in 255. The main findings of this study were: (1) Patients with AD without ACLF showed very high baseline levels of inflammatory cytokines, HNA2, PRC, and PCC. Patients with ACLF showed significantly higher levels of these markers than those without ACLF; (2) different cytokine profiles were identified according to the type of ACLF precipitating event (active alcoholism/acute alcoholic hepatitis, bacterial infection, and others); (3) severity of SI and frequency and severity of ACLF at enrollment were strongly associated. The course of SI and the course of ACLF (improvement, no change, or worsening) during hospitalization and short-term mortality were also strongly associated; and (4) the strength of association of ACLF with SI was higher than with SCD. CONCLUSION: Our data support SI as the primary driver of ACLF in cirrhosis

Systemic inflammation in decompensated cirrhosis: Characterization and role in acute-on-chronic liver failure.

UNLABELLED Acute-on-chronic liver failure (ACLF) in cirrhosis is characterized by acute decompensation (AD), organ failure(s), and high short-term mortality. Recently, we have proposed (systemic inflammation [SI] hypothesis) that ACLF is the expression of an acute exacerbation of the SI already present in decompensated cirrhosis. This study was aimed at testing this hypothesis and included 522 patients with decompensated cirrhosis (237 with ACLF) and 40 healthy subjects. SI was assessed by measuring 29 cytokines and the redox state of circulating albumin (HNA2), a marker of systemic oxidative stress. Systemic circulatory dysfunction (SCD) was estimated by plasma renin (PRC) and copeptin (PCC) concentrations. Measurements were performed at enrollment (baseline) in all patients and sequentially during hospitalization in 255. The main findings of this study were: (1) Patients with AD without ACLF showed very high baseline levels of inflammatory cytokines, HNA2, PRC, and PCC. Patients with ACLF showed significantly higher levels of these markers than those without ACLF; (2) different cytokine profiles were identified according to the type of ACLF precipitating event (active alcoholism/acute alcoholic hepatitis, bacterial infection, and others); (3) severity of SI and frequency and severity of ACLF at enrollment were strongly associated. The course of SI and the course of ACLF (improvement, no change, or worsening) during hospitalization and short-term mortality were also strongly associated; and (4) the strength of association of ACLF with SI was higher than with SCD. CONCLUSION These data support SI as the primary driver of ACLF in cirrhosis. (Hepatology 2016;64:1249-1264)