Septic Shock Sera Containing Circulating Histones Induce Dendritic Cell–Regulated Necrosis in Fatal Septic Shock Patients

Objectives: Innate immune system alterations, including dendritic cell loss, have been reproducibly observed in patients with septic shock and correlated to adverse outcomes or nosocomial infections. The goal of this study is to better understand the mechanisms behind this observation in order to better assess septic shock pathogenesis.Design: Prospective, controlled experimental study. Setting: Research laboratory at an academic medical center. Subjects: The study enrolled 71 patients, 49 with septic shock and 22 with cardiogenic shock. Seventeen healthy controls served as reference. In vitro monocyte-derived dendritic cells were generated from healthy volunteers. Interventions: Sera were assessed for their ability to promote in vitro dendritic cell death through flow cytometry detection in each group of patients. The percentage of apoptotic or necrotic dendritic cells was evaluated by annexin-V and propidium iodide staining. Measurements and Main Results: We observed that only patients with septic shock and not patients with pure cardiogenic shock were characterized by a rapid and profound loss of circulating dendritic cells. In vitro analysis revealed that sera from patients with septic shock induced higher dendritic cell death compared to normal sera or cardiogenic shock (p < 0.005). Sera from surviving patients induced dendritic cell death through a caspase-dependent apoptotic pathway, whereas sera from nonsurviving patients induced dendritic cell-regulated necrosis. Dendritic cell necrosis was not due to necroptosis but was dependent of the presence of circulating histone. The toxicity of histones toward dendritic cell could be prevented by recombinant human activated protein C. Finally, we observed a direct correlation between the levels of circulating histones in patients and the ability of the sera to promote dendritic cell-regulated necrosis. Conclusions: The study demonstrates a differential mechanism of dendritic cell death in patients with septic shock that is dependent on the severity of the disease

Movements of Hoplias aimara during the filling phase of the Petit-Saut dam, French Guyana

indexedccInternational audienceTwenty Hoplias aimara were tagged intraperitoneally with radio-transmitters in the Sinnamary River, French Guyana. In November 1993, 13 tagged fish were released in an area which would be flooded by the Petit-Saut reservoir impoundment in mid-1994. Seven other tagged fish were released in January 1994, 20 km upstream of the upper limit of the reservoir. Hoplias aimara showed site fidelity: 75% of fish returned to their capture site before the test area was inundated. The remaining fish stayed close to the release area. Monitoring during three 24-h cycles before reservoir filling showed that H. aimara has a limited home range, which is less marked in unconstrained reaches during the wet season (April to August) than in constrained reaches during the dry season (September to November). In natural conditions, H. aimara has a wider home range in unconstrained river reaches than in constrained river reaches. After closure of the dam, in September and October 1994 (dry season, low water) more than half of the total H. aimara tagged in the flooded zone migrated upstream following the rise of water

Identifying factors associated with treatment delay in leptospirosis : a retrospective study of patients admitted to hospital in Reunion (Indian Ocean) between 2014 and 2015

Background. - Leptospirosis is a life-threatening zoonotic disease for which delayed treatment onset has been associated to poor prognosis. The purpose of the study was to identify the determinants of therapeutic delay in hospitalized leptospirosis cases. Patients and methods. - We carried out a retrospective multicenter study in the 4 public hospitals of Reunion Island, South Western Indian Ocean. Medical records of confirmed leptospirosis cases occurring in 2014-2015 were reviewed for socio-economic, demographic, geographic and medical data. The primary outcome measure was the therapeutic delay, defined as the time elapsed between the onset of symptoms and initiation of antibiotics. Results. - Of the 117 patients included, 107 were men, with an average age of 44.9 +/- 15 years. The median therapeutic delay was 4 days (interquartile: 2-5 days) and this delay was not found to be associated with severity. The following were found to be at increased risk of having a longer therapeutic delay: cases occurring outside the epidemic period, or rainy season (OR 2.8 [1.08-7.3], P = 0.04) and cases with first medical evaluation in primary health care (OR 4.63 [1.43-14.93]; P = 0.01) instead of emergency unit. Nosocio-economic or geographic characteristics were found to be linked to a longer therapeutic delay. Conclusion. - Although delayed treatment was not associated to disease severity, our results indicate that leptospirosis awareness is needed all year in the subtropical area of Reunion Island and particularly in primary care