Center Hospitalier University Bicetre

Le Kremlin-Bicêtre, France

Center Hospitalier University Bicetre

Le Kremlin-Bicêtre, France
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Saliou G.,Center Hospitalier University Bicetre | Krings T.,University of Toronto
Handbook of clinical neurology | Year: 2016

Spinal vascular diseases are rare but potentially devastating diseases affecting the cord. This chapter gives an overview about their imaging features, differential diagnoses, the neurologic symptomatology, and the potential therapeutic approaches of these diseases, which might vary depending on the underlying pathologic condition. © 2016 Elsevier B.V. All rights reserved.


Khellaf M.,University Paris Est Creteil | Charles-Nelson A.,University Paris Est Creteil | Fain O.,University of Paris 13 | Terriou L.,Lille University Hospital Center | And 21 more authors.
Blood | Year: 2014

We conducted a prospective multicenter registry of 248 adult patients with immune thrombocytopenia (ITP) treated with rituximab to assess safety. We also assessed response and predictive factors of sustained response. In total, 173 patients received 4 infusions of 375 mg/m2 and 72 received 2 fixed 1-g infusions 2 weeks apart. The choice of the rituximab regimen was based on the physician's preference and not patient characteristics. Overall, 38 patients showed minor intolerance to rituximab infusions; infusions had to be stopped for only 3 patients. Seven showed infection (n = 11 cases), with an incidence of 2.3 infections/100 patient-years. Three patients died of infection 12 to 14 months after rituximab infusions, but the role of rituximab was questionable. In total, 152 patients (61%) showed an overall initial response (platelet count ≥30 x 109/L and ≥2 baseline value). At a median follow-up of 24 months, 96 patients (39%) showed a lasting response. On multivariate analysis, the probability of sustained response at 1 year was significantly associated with ITP duration <1 year (P = .02) and previous transient complete response to corticosteroids (P = .05). The pattern of response was similar with the 2 rituximab regimens. With its benefit/risk ratio, rituximab used off-label may remain a valid option for treating persistent or chronic ITP in adults. This trial was registered at www.clinicaltrials.gov as #NC1101295. © 2014 by The American Society of Hematology.


Hescot S.,French Institute of Health and Medical Research | Seck A.,Gustave Roussy | Guerin M.,French Institute of Health and Medical Research | Cockenpot F.,Gustave Roussy | And 8 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2015

Context: Mitotane (o,p′-DDD), the only approved drug for advanced adrenocortical carcinoma (ACC), is a lipophilic agent that accumulates into circulating lipoprotein fractions and high-lipid-containing tissues. Objective: The aim of our study was to evaluate the in vivo and in vitro biological implication of serum lipoproteins on pharmacological action of mitotane. Distribution and concentration of mitotane were studied in plasma and adrenal tissue samples from mitotane-treated patients. The effect of lipoprotein-bound or lipoprotein-free (LP-F) mitotane was analyzed on proliferation and apoptosis of human adrenocortical H295R cells. A retrospective study of patients with ACC treated or not with statins was also performed. Results: o,p′-DDD distribution among very low-density lipoprotein, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and LP-F fractions obtained after plasma ultracentrifugation of 23 of mitotane-treated patients was widely distributed in each subfraction. A positive correlation was observed between mitotane levels in plasma and in LDL, HDL, but also LP-F compartment. Intratumor o,p′-DDD concentrations in five ACC samples of mitotane-treated patients were found to be independent of cholesterol transporter expression, scavenger receptors, and LDL receptors. In vitro studies showed significant higher antiproliferative and proapoptotic effects and higher cell and mitochondrial uptake of mitotane when H295R cells were grown in LP-F medium. Finally, retrospective study of an ACC cohort of 26 mitotane-treated patients revealed that statin therapy was significantly associated with a higher rate of tumor control. Conclusions: Altogether, our in vitro and in vivo studies provided compelling evidence for a greater efficacy of LP-F mitotane. Patients with ACC may thus benefit from therapeutic strategies that aim to increase LP-F mitotane fraction. Copyright © 2015 by the Endocrine Society.


PubMed | Center Hospitalier University Estaing, University of Bordeaux 1, Groupement Hospitalier Edouard Herriot, Center Hospitalier University Necker and 14 more.
Type: Clinical Trial | Journal: Blood | Year: 2014

We conducted a prospective multicenter registry of 248 adult patients with immune thrombocytopenia (ITP) treated with rituximab to assess safety. We also assessed response and predictive factors of sustained response. In total, 173 patients received 4 infusions of 375 mg/m(2) and 72 received 2 fixed 1-g infusions 2 weeks apart. The choice of the rituximab regimen was based on the physicians preference and not patient characteristics. Overall, 38 patients showed minor intolerance to rituximab infusions; infusions had to be stopped for only 3 patients. Seven showed infection (n = 11 cases), with an incidence of 2.3 infections/100 patient-years. Three patients died of infection 12 to 14 months after rituximab infusions, but the role of rituximab was questionable. In total, 152 patients (61%) showed an overall initial response (platelet count 30 10(9)/L and 2 baseline value). At a median follow-up of 24 months, 96 patients (39%) showed a lasting response. On multivariate analysis, the probability of sustained response at 1 year was significantly associated with ITP duration <1 year (P = .02) and previous transient complete response to corticosteroids (P = .05). The pattern of response was similar with the 2 rituximab regimens. With its benefit/risk ratio, rituximab used off-label may remain a valid option for treating persistent or chronic ITP in adults. This trial was registered at www.clinicaltrials.gov as #NC1101295.


Kasteleijn- Nolst Trenite D.,University of Rome La Sapienza | Kasteleijn- Nolst Trenite D.,University Utrecht | Parain D.,University of Rouen | Genton P.,Center Saint Paul | And 3 more authors.
Epilepsy and Behavior | Year: 2013

A new class of drugs, the nonimidazole histamine 3 receptor (H3R) antagonists, has been developed in the past decade for treatment of various brain diseases. Pitolisant is such a drug.We studied the pharmacodynamic effect of pitolisant in patients with epilepsy in early Phase II, using the photosensitivity proof of concept model. A total of 14 adult patients (11 females and 3 males; 5 drug naïve) were studied for three days to evaluate the effect of a single oral dose of pitolisant on EEG photosensitivity ranges. All patients showed repeatedly a generalized photoparoxysmal response (PPR) prior to drug administration on placebo Day 1. A statistically significant suppressive effect (standardized photosensitive response [SPR] reduction as measured with paired t-tests) for 20-, 40-, or 60-mg doses of pitolisant was seen in 9/14 (64%) patients of whom 6/14 (43%) showed abolition of the response to intermittent photic stimulation (IPS). Patients on the highest dosage (60. mg) showed the strongest effect with an effect lasting up to 28. h. Thus, full-scale Phase II studies with this novel H3R antagonist, pitolisant, in patients with epilepsy are warranted. © 2013 Elsevier Inc.


Carbonne A.,Regional Coordinating Center for Nosocomial Infection Control | Thiolet J.M.,Institute of Veille Sanitaire | Fournier S.,Central infection control team | Fortineau N.,Center Hospitalier University Bicetre | And 12 more authors.
Eurosurveillance | Year: 2010

An outbreak of Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae type 2 was detected in September 2009 in two hospitals in a suburb south of Paris, France. In total, 13 KPC-producing K. pneumoniae type 2 cases (four with infections and nine with digestive-tract colonisations) were identified, including a source case transferred from a Greek hospital. Of the 13 cases, seven were secondary cases associated with use of a contaminated duodenoscope used to examine the source case (attack rate: 41%) and five were secondary cases associated with patient-topatient transmission in hospital. All isolated strains from the 13 patients: (i) exhibited resistance to all antibiotics except gentamicin and colistin, (ii) were more resistant to ertapenem (minimum inhibitory concentration (MIC) always greater than 4 mg/L) than to imipenem (MIC: 1-8 mg/L, depending on the isolate), (iii) carried the blaKPC-2 and blaSHV12 genes and (iv) had an indistinguishable pulsed-field gel electrophoresis (PFGE) pattern. These cases occurred in three hospitals: some were transferred to four other hospitals. Extended infection control measures implemented in the seven hospitals included: (i) limiting transfer of cases and contact patients to other wards, (ii) cohorting separately cases and contact patients, (iii) reinforcing hand hygiene and contact precautions and (iv) systematic screening of contact patients. Overall, 341 contact patients were screened. A year after the outbreak, no additional case has been identified in these seven hospitals. This outbreak emphasises the importance of rapid identification and notification of emerging highly resistant K. pneumoniae strains in order to implement reinforced control measures.


Gonzalez-Aguilar A.,Groupe Hospitalier Pitie Salpetriere | Gonzalez-Aguilar A.,University Pierre and Marie Curie | Idbaih A.,Groupe Hospitalier Pitie Salpetriere | Idbaih A.,University Pierre and Marie Curie | And 27 more authors.
Clinical Cancer Research | Year: 2012

Purpose: Our objective was to identify the genetic changes involved in primary central nervous system lymphoma (PCNSL) oncogenesis and evaluate their clinical relevance. Experimental Design: We investigated a series of 29 newly diagnosed, HIV-negative, PCNSL patients using high-resolution single-nucleotide polymorphism (SNP) arrays (n = 29) and whole-exome sequencing (n = 4) approaches. Recurrent homozygous deletions and somatic gene mutations found were validated by quantitative real-time PCR and Sanger sequencing, respectively. Molecular results were correlated with prognosis. Results: All PCNSLs were diffuse large B-cell lymphomas, and the patients received chemotherapy without radiotherapy as initial treatment. The SNP analysis revealed recurrent large and focal chromosome imbalances that target candidate genes in PCNSL oncogenesis. The most frequent genomic abnormalities were (i) 6p21.32 loss (HLA locus), (ii) 6q loss, (iii) CDKN2A homozygous deletions, (iv) 12q12-q22, and (v) chromosome 7q21 and 7q31 gains. Homozygous deletions of PRMD1 , TOX, and DOCK5 and the amplification of HDAC9 were also detected. Sequencing of matched tumor and blood DNA samples identified novel somatic mutations in MYD88 and TBL1XR1 in 38% and 14% of the cases, respectively. The correlation of genetic abnormalities with clinical outcomes using multivariate analysis showed that 6q22 loss (P = 0.006 and P = 0.01) and CDKN2A homozygous deletion (P = 0.02 and P = 0.01) were significantly associated with shorter progression-free survival and overall survival. Conclusions: Our study provides new insights into the molecular tumorigenesis of PCNSL and identifies novel genetic alterations in this disease, especially MYD88 and TBL1XR1 mutations activating the NF-κB signaling pathway, which may be promising targets for future therapeutic strategies. ©2012 AACR.


PubMed | University of Bordeaux 1, Paris-Sorbonne University, Assistance Publique Hopitaux de Paris, Institut Universitaire de France and 7 more.
Type: Journal Article | Journal: Oncotarget | Year: 2014

Little is known about the genomic basis of primary central nervous system lymphoma (PCNSL) tumorigenesis. To investigate the mutational profile of PCNSL, we analyzed nine paired tumor and germline DNA samples from PCNSL patients by high throughput exome sequencing. Eight genes of interest have been further investigated by focused resequencing in 28 additional PCNSL tumors to better estimate their incidence. Our study identified recurrent somatic mutations in 37 genes, some involved in key signaling pathways such as NFKB, B cell differentiation and cell cycle control. Focused resequencing in the larger cohort revealed high mutation rates for genes already described as mutated in PCNSL such as MYD88 (38%), CD79B (30%), PIM1 (22%) and TBL1XR1 (19%) and for genes not previously reported to be involved in PCNSL tumorigenesis such as ETV6 (16%), IRF4 (14%), IRF2BP2 (11%) and EBF1 (11%). Of note, only 3 somatically acquired SNVs were annotated in the COSMIC database. Our results demonstrate a high genetic heterogeneity of PCNSL and mutational pattern similarities with extracerebral diffuse large B cell lymphomas, particularly of the activated B-cell (ABC) subtype, suggesting shared underlying biological mechanisms. The present study provides new insights into the mutational profile of PCNSL and potential targets for therapeutic strategies.


Blanie A.,Center Hospitalier University Bicetre | Ract C.,Center Hospitalier University Bicetre | Leblanc P.-E.,Center Hospitalier University Bicetre | Cheisson G.,Center Hospitalier University Bicetre | And 6 more authors.
Anesthesia and Analgesia | Year: 2012

Background: Urgent tracheal intubations are common in intensive care units (ICU), and succinylcholine is one of the first-line neuromuscular blocking drugs used in these situations. Critically ill patients could be at high risk of hyperkalemia after receiving succinylcholine because one or more etiologic factors of nicotinic receptor upregulation can be present, but there are few data on its real risk. Our objectives in this study were to determine the factors associated with arterial potassium increase (ΔK) and to assess the occurrence of acute hyperkalemia ≥6.5 mmol/L after succinylcholine injection for intubation in the ICU. Methods: In a prospective, observational study, all critically ill patients intubated with succinylcholine in an ICU were screened. Only intubations with arterial blood gases and potassium measurements before and after (Kafter) a succinylcholine injection were studied. Results: During 18 months, 131 critically ill patients were intubated after receiving succinylcholine with arterial potassium before and after intubation (K after) for a total of 153 intubations. After multivariate analysis, the only factor associated with ΔK was the length of ICU stay before intubation (ρ = 0.561, P < 0.001). The factors associated with K after ≥6.5 mmol/L (n = 11) were the length of ICU stay (P < 0.001) and the presence of acute cerebral pathology (P = 0.047). The threshold of 16 days was found highly predictive of acute hyperkalemia ≥6.5 with 37% (95% confidence interval: 19%-58%) of Kafter ≥6.5 after the 16th day compared with only 1% (95% confidence interval: 0%-4%) of Kafter ≥6.5 when succinylcholine was injected during the first 16 days. Conclusions: This study shows that the risk of ΔK after succinylcholine injection is strongly associated with the length of ICU stay. The risk of acute hyperkalemia ≥6.5 mmol/L is highly significant after 16 days. Copyright © 2012 International Anesthesia Research Society.


Toulgoat F.,Center Hospitalier University Bicetre | Lasjaunias P.,Center Hospitalier University Bicetre
Handbook of Clinical Neurology | Year: 2013

Pediatric neurovascular malformations are rare. However, proper diagnosis and management are mandatory to achieve a good neurocognitive outcome. Among them several types can be identified with specificities for each. In the newborn and infancy, the most frequent cerebral venous malformation is vein of Galen aneurysmal malformation. It can be discovered antenatally, in neonates (mainly in cases with hemodynamic impact), or in infants presenting with macrocrania and hydrocephalus. Treatment of choice is endovascular, by transarterial selective occlusion of pathological vessels. Interventions are staged with a first session at around 5 months, adjusted to neurological development. Late consequences, especially if left untreated or treated outside the therapeutic window, are delayed neurocognitive development and seizures. Pial arteriovenous malformation can also be diagnosed antenatally. Regional parenchymal destruction could occur in the first months of life, requiring early endovascular treatment. Dural sinus malformations are the third main type of neurovascular malformation, and are also diagnosed antenatally or in the first months of life. Cardiac tolerance is usually good. Adverse consequences are mainly neurocognitive delay due to chronic venous hyperpressure or acute hemorrhage due to thrombosis of the pathological sinuses. Nidal-type brain arteriovenous malformation and cavernous angioma are usually seen later in children, with hemorrhage often being the first presenting symptom. © 2013 Elsevier B.V.

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