Un nouvel espoir dans le traitement de l’hémophilie A. Expression du facteur VIII dans des précurseurs plaquettaires myéloïdes

International audienceNo abstract availabl

A cohort study of banana plantation workers in the French West Indies: first mortality analysis (2000-2015)

International audienceChlordecone, an organochlorine insecticide, was widely used in the French West Indies banana plantations. We set up a cohort of banana plantation workers who worked between 1973 and 1993, the period of authorized use of chlordecone. Vital status and causes of death were collected from French national registries. Workers were followed up from 1 January 2000 to 31 December 2015. Cause-specific mortality in the cohort was compared to that of the general population of the French West Indies by computing standardized mortality ratios (SMRs). A total of 11,112 workers (149,526 person-years, 77% men) were included in the mortality analysis, and 3647 deaths occurred over the study period. There was a slight deficit in all-cause mortality, which was statistically significant in men (SMR = 0.93, 95% CI 0.89-0.96), but not in women (SMR = 0.96, 95% CI 0.89-1.04). All-cancer mortality did not differ significantly from that of the general population (men SMR = 0.96, 95% CI 0.90-1.03; women SMR = 1.04, 95% CI 0.89-1.21). Significant excesses of deaths were observed for stomach cancer in women (SMR = 1.94, 95% CI 1.24-2.89) and pancreatic cancer in women farm owners (SMR = 2.31, 95% CI 1.06-4.39). Mortality from prostate cancer was similar to that of the general population in the whole cohort (SMR = 1.00; 95% CI 0.89-1.13) and non-significantly elevated among farm workers (SMR = 1.10, 95% CI 0.87-1.36). Non-significant increases in mortality were also observed for lung cancer in women, leukemia in men, and non-Hodgkin lymphoma in both genders

Characteristics and outcome of adults with severe autoimmune hemolytic anemia admitted to the intensive care unit: Results from a large French observational study

Adult'autoimmune hemolytic anemia (AIHA), which is often seen as a rare and "benign" autoimmune hematological disease, can be lifethreatening with an overall mortality rate from 8% to 20% depending on the series 1-3 and a short-term mortality rate that can be up to 30% in intensive care units (ICUs). 4 Factors associated with the need for ICU management of patients with severe AIHA remain partially unknown because only few data are available in the literature. 3-5 The aims of this retrospective observational multicenter study set up by the French reference center for adult immune cytopenias were to: (1) better describe the baseline characteristics and outcome of adults with severe AIHA admitted to an ICU, (2) investigate the factors associated with mortality in the ICU, and (3) identify factors at AIHA diagnosis associated with admission to an ICU. To be included in the study, patients had to (1) be ≥16 years old at the time of AIHA onset; (2) have a diagnosis of AIHA defined as hemoglobin level <12 g/dL, with ≥2 features of hemolysis among low haptoglobin level and/or elevated lactate dehydrogenase (LDH) level and/or elevated free bilirubin level, and a positive direct antiglobulin test (DAT) with no other cause of acquired or hereditary hemolytic anemia; and (3) at least one admission to an ICU specifically for AIHA management between January 2013 and December 2020. We excluded patients with nonautoimmune hemolytic anemia, DAT-negative AIHA and drug-induced immune hemolytic anemia and those admitted to the ICU for another reason than severity of AIHA. Baseline data in the ICU included the Charlson Comorbidity Index, the Knaus score, the Sequential Organ Failure Assessment (SOFA), and Simplified Acute Physiology Scor

Hydrocortisone plus fludrocortisone for community acquired pneumonia-related septic shock: a subgroup analysis of the APROCCHSS phase 3 randomised trial

International audienceBackground: Glucocorticoids probably improve outcomes in patients hospitalised for community acquired pneumonia (CAP). In this a priori planned exploratory subgroup analysis of the phase 3 randomised controlled Activated Protein C and Corticosteroids for Human Septic Shock (APROCCHSS) trial, we aimed to investigate responses to hydrocortisone plus fludrocortisone between CAP and non-CAP related septic shock.Methods: APROCCHSS was a randomised controlled trial that investigated the effects of hydrocortisone plus fludrocortisone, drotrecogin-alfa (activated), or both on mortality in septic shock in a two-by-two factorial design; after drotrecogin-alfa was withdrawn on October 2011, from the market, the trial continued on two parallel groups. It was conducted in 34 centres in France. In this subgroup study, patients with CAP were a preselected subgroup for an exploratory secondary analysis of the APROCCHSS trial of hydrocortisone plus fludrocortisone in septic shock. Adults with septic shock were randomised 1:1 to receive, in a double-blind manner, a 7-day treatment with daily administration of intravenous hydrocortisone 50 mg bolus every 6h and a tablet of 50 μg of fludrocortisone via the nasogastric tube, or their placebos. The primary outcome was 90-day all-cause mortality. Secondary outcomes included all-cause mortality at intensive care unit (ICU) and hospital discharge, 28-day and 180-day mortality, the number of days alive and free of vasopressors, mechanical ventilation, or organ failure, and ICU and hospital free-days to 90-days. Analysis was done in the intention-to-treat population. The trial was registered at ClinicalTrials.gov (NCT00625209).Findings: Of 1241 patients included in the APROCCHSS trial, CAP could not be ruled in or out in 31 patients, 562 had a diagnosis of CAP (279 in the placebo group and 283 in the corticosteroid group), and 648 patients did not have CAP (329 in the placebo group and 319 in the corticosteroid group). In patients with CAP, there were 109 (39%) deaths of 283 patients at day 90 with hydrocortisone plus fludrocortisone and 143 (51%) of 279 patients receiving placebo (odds ratio [OR] 0·60, 95% CI 0·43-0·83). In patients without CAP, there were 148 (46%) deaths of 319 patients at day 90 in the hydrocortisone and fludrocortisone group and 157 (48%) of 329 patients in the placebo group (OR 0·95, 95% CI 0·70-1·29). There was significant heterogeneity in corticosteroid effects on 90-day mortality across subgroups with CAP and without CAP (p=0·046 for both multiplicative and additive interaction tests; moderate credibility). Of 1241 patients included in the APROCCHSS trial, 648 (52%) had ARDS (328 in the placebo group and 320 in the corticosteroid group). There were 155 (48%) deaths of 320 patients at day 90 in the corticosteroid group and 186 (57%) of 328 patients in the placebo group. The OR for death at day 90 was 0·72 (95% CI 0·53-0·98) in patients with ARDS and 0·85 (0·61-1·20) in patients without ARDS (p=0·45 for multiplicative interaction and p=0·42 for additive interaction). The OR for observing at least one serious adverse event (corticosteroid group vs placebo) within 180 days post randomisation was 0·64 (95% CI 0·46-0·89) in the CAP subgroup and 1·02 (0·75-1·39) in the non-CAP subgroup (p=0·044 for multiplicative interaction and p=0·042 for additive interaction).Interpretation: In a pre-specified subgroup analysis of the APROCCHSS trial of patients with CAP and septic shock, hydrocortisone plus fludrocortisone reduced mortality as compared with placebo. Although a large proportion of patients with CAP also met criteria for ARDS, the subgroup analysis was underpowered to fully discriminate between ARDS and CAP modifying effects on mortality reduction with corticosteroids. There was no evidence of a significant treatment effect of corticosteroids in the non-CAP subgroup.Funding: Programme Hospitalier de Recherche Clinique of the French Ministry of Health, by Programme d'Investissements d'Avenir, France 2030, and IAHU-ANR-0004