Center Hospitalier University Pitie Salpetriere

Paris, France

Center Hospitalier University Pitie Salpetriere

Paris, France
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Montalescot G.,Institut Universitaire de France | Collet J.-P.,Institut Universitaire de France | Ecollan P.,Center Hospitalier University Pitie Salpetriere | Bolognese L.,Azienda Ospedaliera | And 10 more authors.
Journal of the American College of Cardiology | Year: 2014

Background After percutaneous coronary intervention (PCI) for non-ST-segment elevation myocardial infarction (NSTEMI), treatment with a P2Y12 antagonist with aspirin is recommended for 1 year.Objectives The oral P2Y12 antagonists ticagrelor and prasugrel have higher recommendations than clopidogrel, but it is unknown if administration before the start of PCI is beneficial.Methods In the randomized, double-blind ACCOAST (A Comparison of prasugrel at the time of percutaneous Coronary intervention Or as pre-treatment At the time of diagnosis in patients with non-ST-segment elevation myocardial infarction) trial, 4,033 patients were diagnosed with NSTEMI and 68.7% underwent PCI; 1,394 received pre-treatment with prasugrel (30-mg loading dose), and 1,376 received placebo. At the time of PCI, patients who received pre-treatment with prasugrel received an additional 30-mg dose of prasugrel, and those who received placebo received a 60-mg loading dose of prasugrel. Primary efficacy was a composite of cardiovascular death, myocardial infarction, stroke, urgent revascularization, or glycoprotein IIb/IIIa bailout through 7 days from randomization. Investigators captured the presence of thrombus on initial angiography and during PCI.Results The incidence of the primary endpoint through 7 days from randomization in the pre-treatment group versus the no pre-treatment group was 13.1% versus 13.1% (p = 0.93). Pre-treatment with prasugrel was not associated with decreases in any ischemic event, including total mortality. Patients with thrombus on angiography had a 3-fold higher incidence of the primary endpoint than patients without thrombus. There was no impact of pre-treatment with prasugrel on the presence of thrombus before PCI or on occurrence of stent thrombosis after PCI. There was a 3-fold increase in all non-coronary artery bypass graft Thrombolysis In Myocardial Infarction (TIMI) major bleeding and a 6-fold increase in non-coronary artery bypass graft life-threatening bleeding with pre-treatment with prasugrel; the same trends persisted in patients who had radial or femoral access even with use of a closure device.Conclusions These findings support deferring treatment with prasugrel until a decision is made about revascularization in patients with NSTEMI undergoing angiography within 48 h of admission. (A Comparison of prasugrel at the time of percutaneous Coronary intervention Or as pre-treatment At the time of diagnosis in patients with non - ST-segment elevation myocardial infarction [ACCOAST]; NCT01015287). © 2014 American College of Cardiology Foundation.


Le Manach Y.,Center Hospitalier University Pitie Salpetriere | Hofer C.K.,Triemli City Hospital | Vallet B.,Lille University of Science and Technology | Goarin J.-P.,Center Hospitalier University Pitie Salpetriere | And 2 more authors.
Anesthesiology | Year: 2012

Background: Cardiac output (CO) is rarely monitored during surgery, and arterial pressure remains the only hemodynamic parameter for assessing the effects of volume expansion (VE). However, whether VE-induced changes in arterial pressure accurately reflect changes in CO has not been demonstrated. The authors studied the ability of VE-induced changes in arterial pressure and in pulse pressure variation to detect changes in CO induced by VE in the perioperative period. Methods: The authors studied 402 patients in four centers. Hemodynamic variables were recorded before and after VE. Response to VE was defined as more than 15% increase in CO. The ability of VE-induced changes in arterial pressure to detect changes in CO was assessed using a gray zone approach. Results : VE increased CO of more than 15% in 205 patients (51%). Areas under the receiver operating characteristic curves for VE-induced changes in systolic, diastolic, means, and pulse pressure ranged between 0.64 and 0.70, and sensitivity and specificity ranged between 52 and 79%. For these four arterial pressure-derived parameters, large gray zones were found, and more than 60% of the patients lay within this inconclusive zone. A VE-induced decrease in pulse pressure variation of 3% or more allowed detecting a fluid-induced increase in CO of more than 15% with a sensitivity of 90% and a specificity of 77% and a gray zone between 2.2 and 4.7% decrease in pulse pressure variation including 14% of the patients. Conclusion: Only changes in pulse pressure variation accurately detect VE-induced changes in CO and have a potential clinical applicability. © 2012, the American Society of Anesthesiologists, Inc.


Marie I.,University of Rouen | Josse S.,University of Rouen | Hatron P.Y.,Lille University of Science and Technology | Dominique S.,University of Rouen | And 7 more authors.
Arthritis Care and Research | Year: 2013

Objective To assess the outcome of interstitial lung disease (ILD) in anti-Jo-1 patients with antisynthetase syndrome, determine predictive variables of ILD deterioration in these patients, and compare features of anti-Jo-1 patients with and without ILD. Methods Ninety-one anti-Jo-1 patients were identified by medical records search in 4 medical centers. All of these patients had undergone pulmonary function tests (PFTs) and high-resolution computed tomography (HRCT) scans. Results Sixty-six patients (72.5%) had ILD. Patients could be divided into 3 groups according to their presenting lung manifestations: acute onset of lung disease (n = 12), progressive onset of lung signs (n = 35), and asymptomatic patients exhibiting abnormalities consistent with ILD on PFTs and HRCT scans (n = 19). Sixteen patients had resolution of ILD; 39 and 11 patients experienced improvement and deterioration of ILD, respectively. ILD led to decreased functional status, since 29.8% of patients exhibited a marked reduction of activities due to ILD and 13.6% had respiratory insufficiency requiring oxygen therapy; 5 of 6 patients died due to ILD complications. Predictive parameters of ILD deterioration were HRCT scan pattern of usual interstitial pneumonia, respiratory muscle involvement, and age ≥55 years. Furthermore, anti-Jo-1 patients with ILD, compared with those without, more frequently exhibited mechanic's hands and lower creatine kinase levels. Conclusion Our findings confirm that ILD is a frequent complication in anti-Jo-1 patients, resulting in high morbidity. We suggest that patients with predictive factors of ILD deterioration may require more aggressive therapy. Finally, anti-Jo-1 patients with ILD, compared with those without, may exhibit a particular clinical phenotype. © 2013 by the American College of Rheumatology.


Rinehart J.,University of California at Irvine | Alexander B.,University of California at Irvine | Manach Y.L.,Center Hospitalier University Pitie Salpetriere | Manach Y.L.,University of Oxford | And 4 more authors.
Critical Care | Year: 2011

Introduction: Dynamic predictors of fluid responsiveness have made automated management of fluid resuscitation more practical. We present initial simulation data for a novel closed-loop fluid-management algorithm (LIR, Learning Intravenous Resuscitator).Methods: The performance of the closed-loop algorithm was tested in three phases by using a patient simulator including a pulse-pressure variation output. In the first phase, LIR was tested in three different hemorrhage scenarios and compared with no management. In the second phase, we compared LIR with 20 practicing anesthesiologists for the management of a simulated hemorrhage scenario. In the third phase, LIR was tested under conditions of noise and artifact in the dynamic predictor.Results: In the first phase, we observed a significant difference between the unmanaged and the LIR groups in moderate to large hemorrhages in heart rate (76 ± 8 versus 141 ± 29 beats/min), mean arterial pressure (91 ± 6 versus 59 ± 26 mm Hg), and cardiac output (CO; (6.4 ± 0.9 versus 3.2 ± 1.8 L/min) (P < 0.005 for all comparisons). In the second phase, LIR intervened significantly earlier than the practitioners (16.0 ± 1.3 minutes versus 21.5 ± 5.6 minutes; P < 0.05) and gave more total fluid (2,675 ± 244 ml versus 1,968 ± 644 ml; P < 0.05). The mean CO was higher in the LIR group than in the practitioner group (5.9 ± 0.2 versus 5.2 ± 0.6 L/min; P < 0.05). Finally, in the third phase, despite the addition of noise to the pulse-pressure variation value, no significant difference was found across conditions in mean, final, or minimum CO.Conclusion: These data demonstrate that LIR is an effective volumetric resuscitator in simulated hemorrhage scenarios and improved physician management of the simulated hemorrhages. © 2011 Cannesson et al.; licensee BioMed Central Ltd.


Lefort B.,French Institute of Health and Medical Research | Lefort B.,University of Tours | Saheb S.,Center Hospitalier University Pitie Salpetriere | Bruckert E.,Center Hospitalier University Pitie Salpetriere | And 4 more authors.
Atherosclerosis | Year: 2015

Background: Homozygous familial hypercholesterolemia (HFH) is a rare genetic disease leading to early onset atherosclerosis, due to high concentrations of LDL-C in the blood. Aortic root atheromas may be complicated by obstruction to left ventricle outflow or coronary stenosis. The aim of this study was to describe the progression of aortic root atheroma in patients requiring lipoprotein apheresis before 16 years of age and to examine the requirement of these patients for aortic surgery. Method: Clinical reports, lipid profiles and echocardiogram results were obtained retrospectively for patients with HFH from three French hemapheresis centers. Data are presented as group medians. Results: Twenty patients were included, of which 53% had aortic root atheroma (as assessed by echocardiogram) before starting lipoprotein apheresis. These patients began lipoprotein apheresis later than children without aortic root atheroma (10.3 years old [range 5.6-15.9 years] vs. 5.0 years old [range 4.5-11.6 years], respectively, p<0.05). After 16.4 years (range 2.2-22.8 years) of lipoprotein apheresis treatment, aortic root atheroma had progressed in 64% of patients. Five patients needed surgery for aortic stenosis, which was associated with a coronary artery by-pass for two of them. There were significantly more operations among patients with an aortic root atheroma at the beginning of lipoprotein apheresis than among patients without preexisting lesions (p<0.01). One patient died after aorta replacement surgery during this period. Conclusion: Our results suggest that the initiation of lipoprotein apheresis before the onset of aortic root atheroma should reduce the requirement for aortic surgery. © 2015 Elsevier Ireland Ltd.


Kirova Y.M.,University Pierre and Marie Curie | Chargari C.,Hopital dInstruction des Armees du Val de Grace | Mazeron J.-J.,Center Hospitalier University Pitie Salpetriere
Bulletin du Cancer | Year: 2011

Whole brain radiotherapy remains standard in the management of breast cancer patients with brain metastases. It allows for symptomatic improvement and good local control in most patients. However, its results remain suboptimal in terms of both efficacy and toxicity.highly selected patients, stereotactic radiotherapy demonstrated very good local control with lowtoxicity. With purpose of improving the efficacy/toxicity ratio, strategies of biomodulation of tumor radiosensitivity were recently developed. First results are promising and warrant further assessment. At the same time, new technologies and new irradiation modalities demonstrated their ability in providing high dosimetric homogeneity, delivering integrated radiation boosts, and avoiding critical structures that are involved in long-term neurological toxicity. Further assessment is required and recruitment of breast cancer patients into clinical trials is encouraged. ©John Libbey Eurotext.


Van Den Bent M.J.,Erasmus University Rotterdam | Dubbink H.J.,Erasmus University Rotterdam | Marie Y.,Center Hospitalier University Pitie Salpetriere | Brandes A.A.,Bellaria Maggiore Hospital | And 11 more authors.
Clinical Cancer Research | Year: 2010

Purpose: Recent studies have shown the prognostic significance of IDH1 mutations in glioma. It is yet unclear if IDH1 mutations are predictive for outcome to chemotherapy. We determined the effect of IDH1 mutations on progression-free survival and overall survival (OS), and its correlation with other clinical and molecular features in the prospective randomized European Organization for Research and Treatment of Cancer study 26951 on adjuvant procarbazine, 1-(2-chloroethyl)-3-cyclohexyl-L-nitrosourea, and vincristine (PCV) in anaplastic oligodendroglioma. Experimental Design: IDH1 and IDH2 alterations of the mutational hotspot codons R132 and R172 were assessed by the bidirectional cycle sequencing of PCR-amplified fragments. MGMT promoter methylation was assessed using methylation-specific multiplex ligation-dependant probe amplification based on methylation-sensitive restriction analysis. Loss of chromosomes 1p, 19q, 10, and 10q and the gain of 7 and the EGFR gene were assessed with fluorescence in situ hybridization. Results: From 159 patients, sufficient material was available for IDH1 analysis. In 151 and 118 of these patients, respectively, the 1p/19q status and the MGMT promoter methylation status were known. In 73 cases (46%), an IDH1 mutation was found and only one IDH2 mutation was identified. The presence of IDH1 mutations correlated with 1p/19q codeletion and MGMT promoter methylation, and inversely correlated with loss of chromosome 10, EGFR amplification, polysomy of chromosome 7, and the presence of necrosis. IDH1 mutations were found to be prognostic in the radiotherapy- and the radiotherapy/PCV-treated patients, for both progression-free survival and OS. With Cox proportional hazard modeling for OS with stepwise selection, IDH1 mutations and 1p/19q codeletion but not MGMT promoter methylation were independent prognostic factors. Conclusion: In this homogeneously treated group of anaplastic oligodendroglioma patients, the presence of IDH1 mutations was found to carry a very strong prognostic significance for OS but without evidence of a predictive significance for outcome to PCV chemotherapy. IDH1 mutations were strongly associated with 1p/ 19q codeletion and MGMT promoter methylation. ©2010 AACR.


Launay-Vacher V.,Center Hospitalier University Pitie Salpetriere | Zimner-Rapuch S.,Center Hospitalier University Pitie Salpetriere | Poulalhon N.,Lyon University Hospital Center | Fraisse T.,CHU Gabriel Montpied | And 5 more authors.
Cancer | Year: 2014

BACKGROUND Vemurafenib is a BRAF inhibitor that has become the cornerstone of metastatic or inoperable melanoma therapy since its approval in 2011 in the United States and 2012 in Europe. This targeted therapy has shown impressive results in terms of increased progression-free and overall survival as compared to dacarbazine. The safety profile did not include any renal manifestations at that time. METHODS This report is the first case series of 8 patients who experienced significant to severe renal insufficiency under vemurafenib treatment. RESULTS This case series shows that vemurafenib may induce potentially severe acute renal failure, including renal sequelae and persistent kidney disease in some cases. CONCLUSIONS Further studies are needed to investigate the effects of vemurafenib on the kidneys. Meanwhile, renal function should be closely monitored in treated patients for early detection of any renal dysfunction occurrence. © 2014 American Cancer Society.


Said G.,Center Hospitalier University Pitie Salpetriere | Plante-Bordeneuve V.,Hopital Henri Mondor
Amyloid | Year: 2012

Transthyretin familial amyloid polyneuropathy is characterized by a devastating sensory-motor polyneuropathy associated with life-threatening autonomic disturbance. An early diagnosis is mandatory to increase the chance to modify the course of the disease. This paper underlines the diagnostic problems encountered in this condition. © 2012 Informa UK, Ltd.


Plante-Bordeneuve V.,Center Hospitalier University Henri Mondor | Said G.,Center Hospitalier University Pitie Salpetriere
The Lancet Neurology | Year: 2011

Familial amyloid polyneuropathies (FAPs) are a group of life-threatening multisystem disorders transmitted as an autosomal dominant trait. Nerve lesions are induced by deposits of amyloid fibrils, most commonly due to mutated transthyretin (TTR). Less often the precursor of amyloidosis is mutant apolipoprotein A-1 or gelsolin. The first identified cause of FAP-the TTR Val30Met mutation-is still the most common of more than 100 amyloidogenic point mutations identified worldwide. The penetrance and age at onset of FAP among people carrying the same mutation vary between countries. The symptomatology and clinical course of FAP can be highly variable. TTR FAP typically causes a nerve length-dependent polyneuropathy that starts in the feet with loss of temperature and pain sensations, along with life-threatening autonomic dysfunction leading to cachexia and death within 10 years on average. TTR is synthesised mainly in the liver, and liver transplantation seems to have a favourable effect on the course of neuropathy, but not on cardiac or eye lesions. Oral administration of tafamidis meglumine, which prevents misfolding and deposition of mutated TTR, is under evaluation in patients with TTR FAP. In future, patients with FAP might benefit from gene therapy; however, genetic counselling is recommended for the prevention of all types of FAP. © 2011 Elsevier Ltd.

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