Protein C concentrations in severe sepsis: an early directional change in plasma levels predicts outcome

INTRODUCTION: Protein C, because of its central role in hemostasis, plays an integral role in the host response to infection. Protein C depletion, resulting from increased consumption, degradation, and/or decreased synthesis, is characteristic of sepsis and has been shown to predict morbidity and mortality. The objective of this study was to determine whether early directional changes in protein C levels correlate with outcome. METHODS: Patients in the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) clinical trial were assessed and categorized by baseline protein C (n = 1574). Deficiency was categorized as: severe deficiency, protein C levels ≤ 40% of normal protein C activity (n = 615, 39% of patients); deficient, protein C levels 41–80% of normal protein C activity (n = 764, 48.5% of patients); and normal, >80% of normal protein C activity (n = 195, 12.4% of patients). Logistic regression analysis of 28-day mortality for placebo patients was used to investigate whether baseline and day 1 protein C levels were independent risk factors for mortality. The impact of treatment with drotrecogin alfa (activated) (DrotAA) was also assessed. RESULTS: Protein C levels at baseline and day 1 were independent risk factors in placebo patients. If baseline protein C levels of severely deficient placebo patients remained ≤ 40% at day 1 their odds of death increased (odds ratio = 2.75, P < 0.0001), while if levels improved to >40% by day 1 their risk of death decreased (odds ratio = 0.43, P = 0.03). If baseline protein C levels of placebo patients were >40% but decreased by ≥ 10% on day 1, their risk of death increased (odds ratio = 1.87, P = 0.02). DrotAA treatment improved protein C levels by day 1 compared with placebo (P = 0.008) and reduced the risk of death in severely deficient (≤ 40%) patients at baseline. Treatment also decreased the number of severely protein C deficient (= 40%) patients and decreased the number of deficient (41–80%) patients and normal (>80%) patients who had a ≥ 10% decrease in protein C levels by day 1. CONCLUSION: Baseline protein C levels were an independent predictor of sepsis outcome. Day 1 changes in protein C, regardless of baseline levels, were also predictive of outcome. The association of DrotAA treatment, increased protein C levels, and improved survival may partially explain the mechanism of action

Universal changes in biomarkers of coagulation and inflammation occur in patients with severe sepsis, regardless of causative micro-organism [ISRCTN74215569]

INTRODUCTION: PROWESS (Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis) was a phase III, randomized, double blind, placebo controlled, multicenter trial conducted in patients with severe sepsis from 164 medical centers. Here we report data collected at study entry for 1690 patients and over the following 7 days for the 840 patients who received placebo (in addition to usual standard of care). METHODS: Nineteen biomarkers of coagulation activation, anticoagulation, fibrinolysis, endothelial injury, and inflammation were analyzed to determine the relationships between baseline values and their change over time, with 28-day survival, and type of infecting causative micro-organism. RESULTS: Levels of 13 of the 19 biomarkers at baseline correlated with Acute Physiology and Chronic Health Evaluation II scores, and nearly all patients exhibited coagulopathy, endothelial injury, and inflammation at baseline. At study entry, elevated D-dimer, thrombin–antithrombin complexes, IL-6, and prolonged prothrombin time were present in 99.7%, 95.5%, 98.5%, and 93.4% of patients, respectively. Markers of endothelial injury (soluble thrombomodulin) and deficient protein C, protein S, and antithrombin were apparent in 72%, 87.6%, 77.8%, and 81.7%, respectively. Impaired fibrinolysis (elevated plasminogen activator inhibitor-1) was observed in 44% of patients. During the first 7 days, increased prothrombin time (which is readily measurable in most clinical settings) was highly evident among patients who were not alive at 28 days. CONCLUSION: Abnormalities in biomarkers of inflammation and coagulation were related to disease severity and mortality outcome in patients with severe sepsis. Coagulopathy and inflammation were universal host responses to infection in patients with severe sepsis, which were similar across causative micro-organism groups

Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Is the pulmonary artery catheter misused? A European view.

To review the problems associated with pulmonary artery catheter use in the intensive care unit; to discuss the need for clinical trials to assess its benefits; and to present original data on the use of the pulmonary artery catheter in European countries.Journal ArticleReviewSCOPUS: no.jinfo:eu-repo/semantics/publishe

Boosting Formaldehyde catalytic oxidation of silica-supported Pt nanoparticles with tailored silanol density

International audienc

Le traitement du choc septique: Aspects hemodynamiques

SCOPUS: re.jinfo:eu-repo/semantics/publishe

A multicenter, double-blind, placebo-controlled. Study of liposomal prostaglandin El (TLC C-53) in patients with acute respiratory distress syndrome

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

On the role of cationic defects over the surface reactivity of manganite-based perovskites for low temperature catalytic oxidation of formaldehyde

International audienceDefect engineering in catalytic materials is a versatile strategy to fine-tune their performance towards oxidation reactions, and break the related bottlenecks. Herein, a series of La1−xMnO3 perovskite-based materials was designedly synthesized to investigate the effect of cation defects on their physico-chemical properties. Based on extensive characterizations and density function theory (DFT) calculations, it is demonstrated that La-deficiency could orderly induce oxygen vacancies and electronic structure regulation on perovskite, which prominently promotes the catalytic activity towards formaldehyde oxidation. The leading material (La0.6MnO3) could retain high activity for 63 h, either under dry or humid air. In brief, this work unveils the feasibility of modulating the surface reactivity by modifying the electronic structure properties of lanthanum manganite perovskites following simple adjustment of the A-site cationic vacancies, and also highlights A-site deficient perovskite as a potentially efficient catalyst for environmental remediation