Assistance Publique Hpitaux de Paris

Paris, France

Assistance Publique Hpitaux de Paris

Paris, France

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Puymirat E.,Assistance Publique Hpitaux de Paris | Puymirat E.,University of Paris Descartes | Assaoui N.,Assistance Publique Hpitaux de Paris | Assaoui N.,University of Paris Descartes | And 10 more authors.
American Journal of Cardiology | Year: 2011

Data are lacking on the efficacy and safety of a loading dose (LD) of clopidogrel in elderly patients with acute myocardial infarction (AMI). FAST-MI is a nationwide registry that was carried out over a 1-month period in 2005 and included consecutive patients with AMI admitted to intensive care units <48 hours from symptom onset in 223 participating centers. We assessed the impact of a clopidogrel LD (<300 mg) compared to a conventional dose (<300 mg) on bleeding, need for blood transfusion, and 30-day and 12-month survivals in 791 elderly patients (<75 years old, mean age 81 ± 4 years, 48% women, 35% with ST-segment elevation MI) included in this registry. Fifty-nine percent (466 patients) received a clopidogrel LD. Follow-up was >99% complete. Major bleeding and blood transfusions were not significantly different in patients who received a clopidogrel LD (3.2% vs 3.7%, p = 0.72; 5.4% vs 6.2%, p = 0.64, respectively). Early mortality was also not significantly different (10.1 vs 10.8, p = 0.76). Using multivariate analyses, clopidogrel LD did not significantly affect major bleeding or transfusion (odds ratio 1.03, 95% confidence interval 0.49 to 2.17, p = 0.94) and 12-month mortality (hazard ratio 1.00, 95% confidence interval 0.72 to 1.40, p = 0.98). In conclusion, the present data showed that in elderly patients admitted for AMI, use of a LD of clopidogrel compared to a conventional dose was not associated with increased in-hospital bleeding, need for transfusion, or mortality. Large-scale randomized trials are still needed to identify the optimal LD of clopidogrel for elderly patients admitted for AMI. © 2011 Elsevier Inc. All Rights Reserved.


Dewachter P.,Assistance Publique Hopitaux de Paris | Dewachter P.,University of Paris Descartes | Castro S.,Assistance Publique Hpitaux de Paris | Castro S.,University of Versailles | And 4 more authors.
British Journal of Anaesthesia | Year: 2011

Methylene blue-treated fresh-frozen plasma (MB-FFP) is mainly used in Europe. The advantage of the methylene blue system is that units can be treated individually. The combined action of methylene blue and illumination is a photodynamic process preventing viral RNA and DNA replication. We report the first immediate allergic hypersensitivity reaction to methylene blue-treated plasma transfusion. The clinical course and subsequent assessment of the allergic reaction, including skin tests and basophil activation test, confirmed methylene blue-induced IgE-mediated anaphylaxis. All immediate reactions after MB-FFP transfusion should be investigated to document the underlying mechanism. © 2011 The Author Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved.


Saliba J.,French Institute of Health and Medical Research | Saliba J.,University Paris - Sud | Saliba J.,Laboratory of Excellence GR Ex | Saint-Martin C.,French Institute of Health and Medical Research | And 64 more authors.
Nature Genetics | Year: 2015

No major predisposition gene for familial myeloproliferative neoplasms (MPN) has been identified. Here we demonstrate that the autosomal dominant transmission of a 700-kb duplication in four genetically related families predisposes to myeloid malignancies, including MPN, frequently progressing to leukemia. Using induced pluripotent stem cells and primary cells, we demonstrate that overexpression of ATG2B and GSKIP enhances hematopoietic progenitor differentiation, including of megakaryocytes, by increasing progenitor sensitivity to thrombopoietin (TPO). ATG2B and GSKIP cooperate with acquired JAK2, MPL and CALR mutations during MPN development. Thus, the germline duplication may change the fitness of cells harboring signaling pathway mutations and increases the probability of disease development. © 2015 Nature America, Inc.


Pillebout E.,CHU St Louis | Alberti C.,University Paris Diderot | Guillevin L.,CHU Cochin | Ouslimani A.,Assistance Publique Hpitaux de Paris | Thervet E.,CHU Necker
Kidney International | Year: 2010

Henoch Schönlein Purpura (HSP) is a common disease in children, usually associated with a good prognosis. In adults there are no prospective studies concerning its prognosis or treatment, especially in cases of severe visceral involvement. Here we compared steroid therapy without or with cyclophosphamide co-treatment in adults with severe HSP in a 12-month, multi-center, prospective, open-label trial that treated 54 adults with biopsy-proven HSP including proliferative glomerulonephritis and severe visceral manifestations. All received steroids; however, 25 were randomized to also receive cyclophosphamide. The primary endpoint that occurred in three patients in each group was complete disease remission defined as zero on the Birmingham Vasculitis Activity Score with no persistent or new clinical and/or biological vasculitis at 6 months. No patient had active visceral involvement. The secondary endpoints were renal outcome, deaths, and adverse events at 12 months. Renal function, proteinuria, safety data, incidence of diabetes, and severe infections were similar between the two groups. At the last follow-up, renal function remained stable. The small population size of our study does not permit definitive conclusions; however, we suggest that treatment of adults with severe HSP by adding cyclophosphamide provides no benefit compared with steroids alone. © 2010 International Society of Nephrology.


Bruckert E.,Assistance Publique Hpitaux de Paris | Duchene E.,Assistance Publique Hpitaux de Paris | Bonnefont-Rousselot D.,Assistance Publique Hpitaux de Paris | Hansel B.,Assistance Publique Hpitaux de Paris | And 3 more authors.
Current Medical Research and Opinion | Year: 2010

Objective: To investigate the effect of fenofibrate on sleep apnoea indices. Methods: Proof-of-concept study comprising a placebo run-in period (1 week, 5 weeks if fibrate washout was required) and a 4-week randomized, double-blind treatment period. Thirty-four subjects (mean age 55 years, body mass index 34kg/m2, fasting triglycerides 3.5mmol/L) with diagnosed sleep apnoea syndrome not treated with continuous positive airways pressure were enrolled and randomized to once daily treatment with fenofibrate (145mg NanoCrystal® tablet) or placebo. Overnight polysomnography, computerized attention/vigilance tests and blood sampling for measurement of lipids, insulin, fasting plasma glucose and fibrinogen were performed at the end of each study period. Clinical trial registration: NCT00816829. Main outcome measures: As this was an exploratory study, a range of sleep variables were evaluated. The apnoea/hypopnoea index (AHI) and percentage of time spent with arterial oxygen saturation (SpO2) <90 were relevant as they have been evaluated in other clinical trials. Other variables included total apnoeas, hypopnoeas and oxygen desaturations, and non-cortical micro-awakenings related to respiratory events per hour. Results: Fenofibrate treatment significantly reduced the percentage of time with SpO2 <90 (from 9.0 to 3.5 vs. 10.0 to 11.5 with placebo, p0.007), although there was no significant change in the AHI (reduction vs. control 14 (95CI-47 to 40, p0.533). Treatment reduced obstructive apnoeas (by 44, from 18.5 at baseline to 15.0 at end of treatment vs. 29.0 to 30.5 on placebo, p0.048), and non-cortical micro-awakenings per hour (from 23.5 to 18.0 vs. 24.0 to 25.0 with placebo, p0.004). Other sleep variables were not significantly influenced by fenofibrate. Key limitations: Exploratory study in patients with mild to moderate sleep apnoea, limited treatment duration; concomitant hypnotic treatment (35); lack of correction for multiplicity of testing. Conclusions: The consistent direction of change in sleep indices in this proof-of-concept study may support further investigation of fenofibrate in moderate to severe sleep apnoea syndrome. © 2010 Informa UK Ltd All rights reserved.


Bats A.S.,University of Paris Descartes | Blons H.,University of Paris Descartes | Narjoz C.,Assistance Publique Hpitaux de Paris | Le Frere-Belda M.-A.,University of Paris Descartes | And 2 more authors.
Anticancer Research | Year: 2014

Aim: To assess the feasibility of Microsatellite Instability (MSI) analysis in uterine cavity washings for detecting endometrial cancer in Lynch syndrome. Materials and Methods: This was a proof-of-concept study in Lynch syndrome patients, scheduled for hysterectomy. At the beginning of surgical procedure, uterine cavity washings were performed, and sent for MSI analysis. Pathological examination of the uterus was associated with mismatch repair protein expression and MSI analysis. Results; Nine patients were included in the study. Uterine cavity washings were feasible and interpretable in all cases. Final histological report identified 2 endometrial cancers and 7 benign specimens. There was no atypical hyperplasia. Sensitivity, specificity, positive predictive value, and negative predictive value of MSI analysis in uterine washings reached 100% in all cases. Concordance of MSI presence or absence was absolute between uterine washings and final histology. Conclusion; MSI analysis in uterine cavity washings may be a promising screening tool for Lynch syndromeassociated endometrial cancer diagnosis.

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