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

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

Col\ue9opt\ue8res du Nord de l\u27Afrique

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Les façonnements des parcours de soins menant au démarrage de la dialyse en urgence : croisement des points de vue de médecins généralistes, néphrologues et patients [Conference abstract]

International audienceIntroductionLe démarrage de la dialyse en urgence (DU) reste un problème important dans le parcours de soins des MRC. Adressage tardif, absence de soins néphrologiques et scores de co-morbidité élevés ont été mis en évidence comme facteurs de risque de DU. Cependant, comment ces facteurs surviennent et contribuent à dessiner des trajectoires menant au DU reste inexploré. En mobilisant le discours de patients, médecins généralistes et néphrologues, cette étude qualitative identifie et décrit comment les parcours de soins menant au DU se façonnent.Description/méthodesLe terrain d’enquête était la Bretagne. Trois échantillons ont été constitués et interrogés par entretiens semi-directifs : patients ayant démarré la dialyse en urgence entre 2017 et 2019 (définition du registre REIN), médecins généralistes et néphrologues. L’échantillonnage s’appuyait sur la recherche d’un maximum de diversité de profils socio-économiques de patients et de modes d’exercice et d’ancienneté de professionnels de santé. Une analyse thématique croisée entre les trois corpus de transcriptions a été réalisée.RésultatsVingt patients, 12 médecins généralistes et 18 néphrologues ont été interrogés. Cinq thèmes ont été identifiés : (1) l’apprentissage de l’objet « dialyse » ; (2) les représentations de la dialyse et des soins néphrologiques comme : (a) une inacceptable rupture biographique, (b) l’effrayante machinerie invasive (c) la goutte d’eau faisant déborder le vase thérapeutique ; (3) l’écart entre la maladie perçue et traitée ; (4) le passage entre les mailles du filet préventif ; (5) l’inévitable imprévisibilité du cours de la MRC.ConclusionCette étude montre comment les trajectoires menant au DU sont le résultat d’interactions entre les représentations construites des patients de la dialyse, le rapport à la sphère médicale et la physiopathologie de la MRC. Ses résultats suggèrent l’intérêt d’une évaluation des programmes d’éducation thérapeutique à la suppléance, un renforcement de l’accompagnement psychologique, mais aussi la conception et le déploiement d’une campagne de sensibilisation centrée sur la santé rénale