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Le Touquet – Paris-Plage, France

Jambou R.,Institute Pasteur Paris | Le Bras J.,Center Hospitalier University Bichat | Randrianarivelojosia M.,Institute Pasteur Of Madagascar
Trends in Parasitology | Year: 2011

Artemisinin combination therapy (ACT) paves the way for new opportunities to eliminate malaria in the tropics. However, the huge increase of ACT consumption raises major concerns about their availability over the next few years. At the same time a decrease in their efficacy has already been reported. Alongside the deployment of multifocal control programs, the process ranging from artemisia crop production to accreditation of new ACT combinations urgently needs to be strengthened to supply sufficient quantities of high-quality drugs. New suppliers will have the opportunity to enter this market to develop new formulations, and bioequivalence studies are required to validate these new formulations. It is thus crucial for national malaria control teams to be able to better scrutinize the dossier of these new formulations. © 2010 Elsevier Ltd.

Ducrocq G.,French Institute of Health and Medical Research | Steg P.-G.,Center Hospitalier University Bichat
Archives of Cardiovascular Diseases Supplements | Year: 2012

Antiplatelet agents play a key role in the management of coronary artery disease. Clopidogrel, in association with aspirin, is a cornerstone of the treatment of patients with acute coronary syndromes and patients treated by angioplasty. However, a heterogeneity of clopidogrel response has been demonstrated. Patients with a low response to clopidogrel have a higher rate of ischaemic events. For this reason, molecules providing faster, stronger and more reproducible inhibition of platelet aggregation have been developed. Among them, prasugrel and ticagrelor have shown promise in phase III clinical trials. Current indications are limited to acute coronary syndromes, with or without ST segment elevation. Prasugrel is restricted to patients treated by angioplasty, whereas ticagrelor can be prescribed irrespective of the strategy. © 2012 Elsevier Masson SAS.

Tchetche D.,University Paul Sabatier | Farah B.,University Paul Sabatier | Misuraca L.,University Paul Sabatier | Pierri A.,University Paul Sabatier | And 14 more authors.
JACC: Cardiovascular Interventions | Year: 2014

Objectives The aim of this study was to analyze the incidence, impact, and predictors of cerebrovascular events (CVEs) in patients undergoing transcatheter aortic valve replacement (TAVR).Background Several issues remain unresolved post-TAVR, including CVEs.Methods The FRANCE-2 (French Aortic Nation CoreValve and Edwards-2) registry prospectively included all patients who underwent TAVR in France and Monaco from January 2010 to October 2011. A total of 3,191 patients were analyzed. Six-month follow-up data were obtained. Events were adjudicated according to Valve Academic Research Consortium (VARC)-1 definition.Results Of the cohort, 3.98% experienced a CVE: 55% were major strokes, 14.5% minor strokes, and 30.5% transient ischemic attacks. The mean delay for CVE occurrence was 2 days (interquartile range: 0 to 7 days) with 48.5% of CVEs occurring within 2 days. There was no statistically significant difference in CVE rate with regard to the type of valve (p = 0.899) and the access route (p = 0.128). Patients with a CVE more frequently had new-onset paroxysmal atrial fibrillation (13.6% vs. 7.6%; p = 0.015). During follow-up, the unadjusted mortality rate was higher in patients with a CVE (26% vs. 16.5%; p = 0.002). By multivariate analysis, only advanced age (odds ratio: 1.05; 95% confidence interval: 1.02 to 1.08; p = 0.02) and having 2 valves implanted (odds ratio: 3.13; 95 confidence interval: 1.40 to 7.05; p = 0.006) were associated with a significant risk of CVEs.Conclusions CVEs occur frequently after TAVR and are associated with an increased mortality rate. No difference exists in the CVE rate when exploring the type of valve or the access route. Advanced age and multiple valves implanted during the same procedure are predictors of CVE. © 2014 American College of Cardiology Foundation Published by Elsevier Inc.

Mammadova-Bach E.,French Institute of Health and Medical Research | Mammadova-Bach E.,University of Strasbourg | Ollivier V.,French Institute of Health and Medical Research | Ollivier V.,University Paris Diderot | And 20 more authors.
Blood | Year: 2015

Fibrin, the coagulation end product, consolidates the platelet plug at sites of vascular injury and supports the recruitment of circulating platelets. In addition to integrin αIIbβ3, another as-yet-unidentified receptor is thought to mediate platelet interaction with fibrin. Platelet glycoprotein VI (GPVI) interacts with collagen and several other adhesive macromolecules. We evaluated the hypothesis that GPVI could be a functional platelet receptor for fibrin. Calibrated thrombin assays using platelet-rich plasma (PRP) showed that tissue factor-triggered thrombin generation was impaired in GPVI-deficient patients and reduced by the anti-GPVI Fab 9O12. Assays on reconstituted PRP and PRP from fibrinogen-deficient patients revealed a fibrinogen-dependent enhancement of thrombin generation, which relied on functional GPVI. The effect of GPVI was found to depend on fibrin polymerization. A binding assay showed a specific interaction between GPVI-Fc and fibrin, inhibited by the Fab 9O12. This Fab also reduced platelet adhesion to fibrin at low (300 s-1) and high (1500 s-1) wall shear rates. Platelets adherent to fibrin displayed shape change, exposure of procoagulant phospholipids, and the formation of small clots. When hirudinated blood was perfused at 1500 s-1 over preformed fibrin-rich clots, the Fab 9O12 decreased the recruitment of platelets by up to 85%. This study identifies GPVI as a platelet receptor for polymerized fibrin with 2 major functions: (1) amplification of thrombin generation and (2) recruitment of circulating platelets to clots. These so-far-unrecognized properties of GPVI confer on it a key role in thrombus growth and stabilization. © 2015 by The American Society of Hematology.

Bessede T.,Center Hospitalier University Henri Mondor | Soulie M.,Toulouse University Hospital Center | Mottet N.,Clinique Mutualiste Saint Etienne | Peyromaure M.,Center Hospitalier University Cochin | And 2 more authors.
Journal of Urology | Year: 2010

Purpose: We analyzed preoperative data, pathological results and followup of pT0 tumors after radical prostatectomy for prostate cancer diagnosed on previous positive biopsy. Materials and Methods: At 6 centers a total of 30 of 7,693 radical prostatectomy specimens were classified as pT0 despite prior biopsy proven prostate cancer. No patients were diagnosed after transurethral prostate resection or received neoadjuvant hormonal treatment. All biopsy cores and radical prostatectomy specimens were reanalyzed by a second pathologist. Followup comprised clinical examination and postoperative prostate specific antigen assay at 1 and 3 months, and every 6 months thereafter. Results: Median patient age was 63 years (range 46 to 73). Median preoperative prostate specific antigen was 7.4 ng/ml (range 1.3 to 23). Of the cases 24 were T1c and 6 were T2a. The median number of biopsy cores was 10 (range 6 to 21) with 1 positive (range 1 to 4). On biopsies median tumor length was 1 mm (range 0.3 to 18) and there was tumor in 11.1% (range 3.4% to 64%). In 25 cases (83.3%) there was only 1 positive biopsy. Gleason score was 3 + 3 in 23 cases and less than 6 in 5 with grade 4 in 2. Only 9 cases filled all nonsignificant tumor criteria. Median specimen weight was 61 gm (range 40 to 160). At a median 82-month followup (range 14 to 226) there was no biochemical progression. Conclusions: After biopsy proven cancer pT0 prostate cancer is an unpredictable pathological finding. Despite its excellent prognosis it has medicolegal repercussions that justify DNA based tissue analysis. There is no evidence that finding focal cancer after extensive prostate resection changes patient prognosis and postoperative treatment. © 2010 American Urological Association Education and Research, Inc.

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