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.

Prevalence and incidence rates of pressure ulcers in an Emergency Department.

Older patients represent an increasing population in emergency department (ED) with underlying diseases and longer ED length of stay, which are potential risk factors of pressure ulcers (PUs). The aim of the study was to determine the prevalence and incidence rates of PUs in an Emergency Department and to analyse variables related to PUs occurrence. The study was carried out in the Emergency Department of Bordeaux (France), and included 602 patients from 1 to 15 June 2010. All the potential body sites of pressure were examined at admission and discharge for all the patients by trained nurses. Comorbidity score, list of treatment, length of stay (hours), PUs (including stage I) and C-reactive protein (CRP) level were systematically recorded. A total of 47 (7·8%) patients had prevalent PUs at admission and 74 (12·3%) at discharge. The cumulative incidence was 4·9% and the incidence density was 5·4 per 1000 patients per hour. In multivariate analysis, higher comorbidities (OR 1·3; P = 0·014) and CRP levels (OR 1·005; P = 0·017) were both independent risk factors for developing PU. In conclusion, these data show that even a very short stay to the ED is sufficient to induce PUs especially stage I.

A Lemierre syndrome variant caused by Staphylococcus aureus.

Lemierre syndrome is a rare clinical entity, characterized by thrombosis of the internal jugular vein that develops after an oropharyngeal infection. We report the case of a 22-year-old woman hospitalized initially for cellulitis of the face. In view of the aggravation of the clinical state (septic shock and multiple organ failure), a computed tomography of the neck was performed and revealed a thrombosis of the right internal and external jugular veins. The patient was treated with antibiotics, heparin, and by a surgical excision for the vascular lesions associated with ligation of jugular veins. The patient completely recovered from her infection.

Life-threatening adverse drug reactions at admission to medical intensive care: a prospective study in a teaching hospital.

OBJECTIVE: To assess the characteristics of life-threatening adverse drug reactions in patients admitted to medical intensive care unit and to define those that could facilitate early identification. DESIGN: A prospective 6-month observational study. PATIENTS: Of the 436 admissions to the teaching hospital medical intensive care unit, all patients aged over 15 years and who had received documented drug treatment were included (n = 405). MEASUREMENTS: Characteristics of patients [age, gender, underlying diseases, organ failure(s), drugs taken, Severity Acute Physiologic Score II, length of stay, outcome at discharge] were prospectively collected using a standardised questionnaire. A panel of experts assessed putative serious adverse drug reaction(s) for each drug taken and each organ failure at admission by using a standardised causality assessment method. Characteristics of patients with and without serious adverse drug reactions at admission were compared using univariate and then stepwise descending multivariate logistic regression. RESULTS: Of the 405 patients included, 111 (27.4%) presented an adverse drug reaction leading to organ failure. In 48% of cases adverse drug reactions were preventable, 23% were undiagnosed and 19% contributed to death. Age over 75 years [odds ratio (OR) 2.25; 95% confidence interval (CI) 1.15-4.38; p = 0.02], having more than three drugs (OR 6.90; 95% CI 1.44-33.00; p = 0.02) and a diagnosis of haematological malignancy (OR 6.19; 95% CI 2.07-18.53; p = 0.001) were independently associated with serious adverse drug reactions. CONCLUSIONS: Preventable life-threatening adverse drug reactions were frequently involved in organ failure at admission to medical intensive care; many of them had not been identified.

Decrease in circulating dendritic cells predicts fatal outcome in septic shock.

OBJECTIVE: Biomarkers allowing accurate early staging of septic shock patients are lacking despite their obvious interest for patient management. Experimental models of septic shock in mouse previously noted a decrease in dendritic cell numbers. The aim of the study was to find a rapid reproducible biological test for an assessment of disease severity. DESIGN: Evaluation of peripheral blood dendritic cell counts by flow cytometry using three commercially available kits. PATIENTS AND PARTICIPANTS: Forty-two consecutive septic shock patients were studied prospectively. MEASUREMENTS AND RESULTS: Early low dendritic cell counts were correlated to disease severity as assessed by Simplified Acute Physiology Score or Sequential Organ Failure Assessment and predicted fatal outcome. The correlation was still present when the results were adjusted for age. CONCLUSION: The monitoring of blood dendritic cell count may provide an early and valuable assessment of the severity of the host response against infection and may influence the therapeutic management of septic shock patients.

Psychotropic drugs use and risk of heat-related hospitalisation.

OBJECTIVE: To assess if use of psychotropic drugs is associated with an increased risk of admission for heat-related pathologies during a heat wave period. METHOD: We conducted a matched case-control study. Cases were defined as subjects admitted to an emergency department for heat-related pathology (hyperthermia or heat stroke) over the August 2003 heat wave. Controls were defined as subjects living in the same area but not hospitalised over the same period and who had at least one prescription form submitted for refunding by the social security insurance in July 2003. Multivariate analyses were used to identify psychotropic drugs independently associated with hospital referral during the heat wave period. RESULTS: Out of the 1405 patients admitted to the emergency department, 56 (4%) presented with heat-related pathology. The mean age of cases was 83 years. Multivariate analyses showed that cases were more likely than controls to be treated with anticholinergic drugs (OR 6.0, 95% CI 1.8-19.6), antipsychotics (OR 4.6, 95% CI 1.9-11.2) or anxiolytics (OR 2.4, 95% CI 1.3-4.4). CONCLUSION: In special risk situations such as heat waves, the risk/benefit ratio of psychotropic drugs which could interfere with body temperature regulation has to be carefully assessed, particularly in the elderly.