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Hausfater P.,Center Hospitalo University Pitie Salpetriere | Hausfater P.,Groupe Hospitalier Pitie Salpetriere | Megarbane B.,Center Hospitalo University Lariboisiere | Dautheville S.,Center Hospitalo University Tenon | And 10 more authors.
Intensive Care Medicine | Year: 2010

Purpose: To identify the prognostic factors associated with mortality in heat-related illness. Methods: Multi-center observational cohort-study in 16 emergency departments (ED) belonging to the teaching hospital network of the Paris area. The cohort comprised all patients admitted to one of the EDs during the August 2003 heat wave in Paris and having a core temperature > 38.5°C. Baseline clinical and biological data in ED, patient's course and 1-year survival rate were recorded. Potential prognostic factors associated with death were assessed by Cox proportional-hazards analysis. Results: A total of 1,456 patients were included. Mean age was 79 ± 19 years. Critically ill conditions were noted in 391 patients (27%), but only 72 (5%) were admitted into an intensive care unit. The survival rate was 57% at 1 year as compared to an expected 90% (P < 0.001). Nine independent prognostic factors were identified: previous treatment with diuretics, living in an institution, age[80 - years, cardiac disease, cancer, core temperature >40°C, systolic arterial pressure <100 mmHg, Glasgow coma scale <12 and transportation to hospital by ambulance. We defined three risk groups: low, intermediate and high risk, with a 1-year survival rate of 85, 61 and 18%, respectively. Conclusions: We observed a low survival rate and developed a risk score based on easily obtained variables that may be useful to clinicians managing casualties from future heat waves. © Copyright jointly hold by Springer and ESICM 2009.


Granger B.,University Pierre and Marie Curie | Granger B.,Center Hospitalo University Pitie Salpetriere | Gueneau L.,French Institute of Health and Medical Research | Gueneau L.,University Pierre and Marie Curie | And 11 more authors.
Human Genetics | Year: 2011

Autosomal dominant Emery-Dreifuss muscular dystrophy is caused by mutations in LMNA gene encoding lamins A and C. The disease is characterized by early onset joint contractures during childhood associated with humero-peroneal muscular wasting and weakness, and by the development of a cardiac disease in adulthood. Important intra-familial variability characterized by a wide range of age at onset of myopathic symptoms (AOMS) has been recurrently reported, suggesting the contribution of a modifier gene. Our objective was to identify a modifier locus of AOMS in relation with the LMNA mutation. To map the modifier locus, we genotyped 291 microsatellite markers in 59 individuals of a large French family, where 19 patients carrying the same LMNA mutation, exhibited wide range of AOMS. We performed Bayesian Markov Chain Monte Carlo-based joint segregation and linkage methods implemented in the Loki© software, and detected a strong linkage signal on chromosome 2 between markers D2S143 and D2S2244 (211 cM) with a Bayes factor of 28.7 (empirical p value = 0.0032). The linked region harbours two main candidate genes, DES and MYL1 encoding desmin and light chain of myosin. Importantly, the impact of the genotype on the phenotype for this locus showed an overdominant effect with AOMS 2 years earlier for the homozygotes of the rare allele and 37 years earlier for the heterozygotes than the homozygotes for the common allele. These results provide important highlights for the natural history and for the physiopathology of Emery-Dreifuss muscular dystrophy. © 2010 Springer-Verlag.


Pallud J.,University Pierre and Marie Curie | Pallud J.,French Institute of Health and Medical Research | Pallud J.,Center Hospitalier Sainte Anne | Pallud J.,University of Paris Descartes | And 35 more authors.
Science Translational Medicine | Year: 2014

Brain gliomas are highly epileptogenic. Excitatory glutamatergic mechanisms are involved in the generation of epileptic activities in the neocortex surrounding gliomas. However, chloride homeostasis is known to be perturbed in glioma cells. Thus, the contribution of γ-aminobutyric acidergic (GABAergic) mechanisms that depend on intracellular chloride merits closer study. We studied the occurrence, networks, cells, and signaling basis of epileptic activities in neocortical slices from the peritumoral surgical margin resected around human brain gliomas. Postoperative glioma tissue from 69% of patients spontaneously generated interictal-like discharges, synchronized, with a high-frequency oscillation signature, in superficial layers of neocortex around areas of glioma infiltration. Interictal-like events depended both on glutamatergic AMPA receptor-mediated transmission and on depolarizing GABAergic signaling. GABA released by interneurons depolarized 65% of pyramidal cells, in which chloride homeostasis was perturbed because of changes in expression of neuronal chloride cotransporters: KCC2 (K-Cl cotransporter 2) was reduced by 42% and expression of NKCC1 (Na-K-2Cl cotransporter 1) increased by 144%. Ictal-like activities were initiated by convulsant stimuli exclusively in these epileptogenic areas. This study shows that epileptic activities are sustained by excitatory effects of GABA in human peritumoral neocortex, as reported in temporal lobe epilepsies, suggesting that both glutamate and GABA signaling and cellular chloride regulation processes, all also involved in oncogenesis as already shown, induce an imbalance between synaptic excitation and inhibition underlying epileptic discharges in glioma patients. Thus, the control of chloride in neurons and glioma cells may provide a therapeutic target for patients with epileptogenic gliomas.


Regnier M.-A.,Center Hospitalo University Pitie Salpetriere | Raux M.,Center Hospitalo University Pitie Salpetriere | Le Manach Y.,Center Hospitalo University Pitie Salpetriere | Asencio Y.,Center Hospitalo University Pitie Salpetriere | And 4 more authors.
Anesthesiology | Year: 2012

BACKGROUND:: Lactate has been shown to be a prognostic biomarker in trauma. Although lactate clearance has already been proposed as an intermediate endpoint in randomized trials, its precise role in trauma patients remains to be determined. METHODS:: Blood lactate levels and lactate clearance (LC) were calculated at admission and 2 and 4 h later in trauma patients. The association of initial blood lactate level and lactate clearance with mortality was tested using receiver-operating characteristics curve, logistic regression using triage scores, Trauma Related Injury Severity Score as a reference standard, and reclassification method. RESULTS:: The authors evaluated 586 trauma patients (mean age 38 ± 16 yr, 84% blunt and 16% penetrating, mortality 13%). Blood lactate levels at admission were elevated in 327 (56%) patients. The lactate clearance should be calculated within the first 2 h after admission as LC0-2 h was correlated with LC0-4 h (R = 0.55, P < 0.001) but not with LC2-4 h (R = 0.04, not significant). The lactate clearance provides additional predictive information to initial blood lactate levels and triage scores and the reference score. This additional information may be summarized using a categorical approach (i.e., less than or equal to-20 %/h) in contrast to initial blood lactate. The results were comparable in patients with high (5 mM/l or more) initial blood lactate. CONCLUSIONS:: Early (0-2 h) lactate clearance is an important and independent prognostic variable that should probably be incorporated in future decision schemes for the resuscitation of trauma patients. © 2012, the American Society of Anesthesiologists, Inc.


PubMed | Aix - Marseille University, University of Helsinki, Center Hospitalo University Pitie Salpetriere, University of Paris Descartes and University Pierre and Marie Curie
Type: Journal Article | Journal: Science translational medicine | Year: 2014

Brain gliomas are highly epileptogenic. Excitatory glutamatergic mechanisms are involved in the generation of epileptic activities in the neocortex surrounding gliomas. However, chloride homeostasis is known to be perturbed in glioma cells. Thus, the contribution of -aminobutyric acidergic (GABAergic) mechanisms that depend on intracellular chloride merits closer study. We studied the occurrence, networks, cells, and signaling basis of epileptic activities in neocortical slices from the peritumoral surgical margin resected around human brain gliomas. Postoperative glioma tissue from 69% of patients spontaneously generated interictal-like discharges, synchronized, with a high-frequency oscillation signature, in superficial layers of neocortex around areas of glioma infiltration. Interictal-like events depended both on glutamatergic AMPA receptor-mediated transmission and on depolarizing GABAergic signaling. GABA released by interneurons depolarized 65% of pyramidal cells, in which chloride homeostasis was perturbed because of changes in expression of neuronal chloride cotransporters: KCC2 (K-Cl cotransporter 2) was reduced by 42% and expression of NKCC1 (Na-K-2Cl cotransporter 1) increased by 144%. Ictal-like activities were initiated by convulsant stimuli exclusively in these epileptogenic areas. This study shows that epileptic activities are sustained by excitatory effects of GABA in human peritumoral neocortex, as reported in temporal lobe epilepsies, suggesting that both glutamate and GABA signaling and cellular chloride regulation processes, all also involved in oncogenesis as already shown, induce an imbalance between synaptic excitation and inhibition underlying epileptic discharges in glioma patients. Thus, the control of chloride in neurons and glioma cells may provide a therapeutic target for patients with epileptogenic gliomas.


Sartorius D.,University of Lyon | Sartorius D.,Lyon University Hospital Center | Le Manach Y.,Center Hospitalo University Pitie Salpetriere | David J.-S.,Lyon University Hospital Center | And 8 more authors.
Critical Care Medicine | Year: 2010

Objectives: Prehospital triage of trauma patients is of paramount importance because adequate trauma center referral improves survival. We developed a simple score that is easy to calculate in the prehospital phase. Design: Multicenter prospective observational study. Setting: Prehospital physician-staffed emergency system in university and nonuniversity hospitals. Interventions: We evaluated 1360 trauma patients receiving care from a prehospital mobile intensive care unit in 22 centers in France during 2002. The association of prehospital variables with in-hospital death was tested using logistic regression, and a simple score (the Mechanism, Glasgow coma scale, Age, and Arterial Pressure [MGAP] score) was created and compared with the triage Revised Trauma Score, Revised Trauma Score, and Trauma Related Injury Severity Score. The model was validated in 1003 patients from 2003 through 2005. Measurements and Main Results: Four independent variables were identified, and each was assigned a number of points proportional to its regression coefficient to provide the MGAP score: Glasgow Coma Scale (from 3-15 points), blunt trauma (4 points), systolic arterial blood pressure (>120 mm Hg: 5 points, 60 to 120 mm Hg: 3 points), and age <60 yrs (5 points). The area under the receiver operating characteristic curve of MGAP was not significantly different from that of the triage Revised Trauma Score or Revised Trauma Score, but when sensitivity was fixed >0.95 (undertriage of 0.05), the MGAP score was more specific and accurate than triage Revised Trauma Score and Revised Trauma Score, approaching those of Trauma Related Injury Severity Score. We defined three risk groups: low (23-29 points), intermediate (18-22 points), and high risk (<18 points). In the derivation cohort, the mortality was 2.8%, 15%, and 48%, respectively. Comparable characteristics of the MGAP score were observed in the validation cohort. Conclusion: The MGAP score can accurately predict in-hospital death in trauma patients. Copyright © 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins.


PubMed | University of Nimes, French Institute of Health and Medical Research, Center Hospitalo University Pitie Salpetriere, Montpellier University and Paris-Sorbonne University
Type: Journal Article | Journal: Anaesthesia, critical care & pain medicine | Year: 2016

Single interscalene blocks (ISB) impair pulmonary function (<24h). We hypothesized that continuous ISBs would prolong pulmonary dysfunction until h48 compared with a single ISB. We compared the time course of spirometric and diaphragmatic dysfunction following single or continuous ISBs.We prospectively included consecutive adult patients scheduled to undergo shoulder surgery under standard general anaesthesia with single (n=30) or continuous (n=31) ISB. Before ISB (baseline), spirometric tests were recorded and the diaphragm course was evaluated with a B-mode ultrasound technique every 12h until h48. ISBs were performed with 15mL 0.5% ropivacaine using an ultrasound technique approach. The continuous group received the same bolus followed by 0.2% ropivacaine 5mLhPatient characteristics were similar in both groups. Thirty minutes after blocks in the PACU, all patients demonstrated a similar and significant unilateral diaphragm paralysis (<25% from baseline). For the primary end point (FVC), no significant difference was observed between groups over the study period. A difference between single and continuous groups was observed at h24 for: FVC (-25%, P=0.038), FEV1s (-24%, P=0.036), diaphragmatic course (-26%, P=0.02), while no differences for other time points (h0-h48) were noted. Clinical respiratory evaluations (respiratory rate, SpOOver infusion, continuous ISB did not significantly prolong unilateral phrenic paresis and demonstrated a limited pulmonary impact.


Delerme S.,Center Hospitalo University Pitie Salpetriere | Freund Y.,Center Hospitalo University Pitie Salpetriere | Renault R.,Center Hospitalo University Pitie Salpetriere | Devilliers C.,Center Hospitalo University Pitie Salpetriere | And 5 more authors.
American Journal of Emergency Medicine | Year: 2010

Background: End-tidal carbon dioxide pressure (etCO2) is widely used in anaesthesia and critical care in intubated patients. The aim of our preliminary study was to evaluate the feasibility of a simple device to predict capnia in spontaneously breathing patients in an emergency department (ED). Patients and methods: This study was a prospective, nonblind study performed in our teaching hospital ED. We included nonintubated patients with dyspnea (≥18 years) requiring measurement of arterial blood gases, as ordered by the emergency physician in charge. There were no exclusion criteria. End-tidal CO2 was measured by an easy-to-use device connected to a microstream capnometer, which gave a continuous measurement and graphical display of the etCO2 level of a patient's exhaled breath. Results: A total of 43 patients (48 measurements) were included, and the majority had pneumonia (n = 12), acute cardiac failure (n = 8), asthma (n = 7), or chronic obstructive pulmonary disease exacerbation (n = 6). Using simple linear regression, the correlation between etCO2 and Paco2 was good (R = 0.82). However, 18 measurements (38%) had a difference between etCO2 and Paco2 of 10 mm Hg or more. The mean difference between the Paco 2 and etCO2 levels was 8 mm Hg. Using the Bland and Altman matrix, the limits of agreement were -10 to +26 mm Hg. Conclusion: In our preliminary study, etCO2 using a microstream method does not seem to accurately predict Paco2 in patients presenting to an ED for acute dyspnea. © 2010 Elsevier Inc. All rights reserved.


Delerme S.,Center Hospitalo University Pitie Salpetriere | Montout V.,Center Hospitalo University Pitie Salpetriere | Goulet H.,Center Hospitalo University Pitie Salpetriere | Arhan A.,Center Hospitalo University Pitie Salpetriere | And 4 more authors.
American Journal of Emergency Medicine | Year: 2012

Background: Transcutaneous carbon dioxide pressure (PtcCO2) has been suggested as a noninvasive surrogate of arterial carbon dioxide pressure (PaCO2). Our study evaluates the reliability of this method in spontaneously breathing patients in an emergency department. Patients and methods: A prospective, observational study was performed in nonintubated dyspneic patients who required measurement of arterial blood gases. Simultaneously and blindly to the physicians in charge, PtcCO2 was measured using a TOSCA 500 monitor (Radiometer, Villeurbanne, France). Agreement between PaCO2 and PtcCO2 was assessed using the Bland-Altman method. Results: Forty-eight patients (mean age, 65 years) were included, and 50 measurements were done. Eleven (23%) had acute heart failure; 10 (21%), pneumonia; 7 (15%), acute asthma; and 7 (15%), exacerbation of chronic obstructive pulmonary disease. Median PaCO2 was 42 mm Hg (range, 17-109). Mean difference between PaCO2 and PtcCO2 was 1 mm Hg with 95% limits of agreement of - 3.4 to + 5.6 mm Hg. All measurement differences were within 5 mm Hg, and 32 (64%) were within 2 mm Hg. Conclusion: Transcutaneous carbon dioxide pressure accurately predicts PaCO2 in spontaneously breathing patients. © 2012 Elsevier Inc. All rights reserved.


PubMed | Center Hospitalo University Pitie Salpetriere and Royal University
Type: | Journal: International orthopaedics | Year: 2016

Some data indicate that first-generation highly cross-linked polyethylene (HXLPE) can oxidise in vivo and is associated with reduced mechanical properties. To overcome these limitations, a natural anti-oxidant vitamin E has been added to HXLPE to preserve the mechanical properties and decrease oxidative degradation whilst conserving high wear resistance. We hypothesised that after a minimal threeyears of follow-up the use of vitamin E-blended HXLPE would result in lower radiographic wear when compared with ultra-high molecular weight polyethylene (UHMWPE).One hundred patients were randomised to receive hybrid total hip arthroplasty (THA) using a monoblock cementless acetabular component made either of UHMWPE or vitamin E-blended HXLPE. All other parameters were identical in both groups. Complete follow-up was available for 74 of these patients. Femoral head penetration was measured using a validated computer-assisted method.The median creep measured 0.111mm (range, -0.576 - +0.444mm) in the vitamin E-blended group versus 0.170mm (range, -0.861 - +0.884mm) in the UHMWPE group (difference of medians, 0.059; p=0.046). The median steady state penetration rate was -0.008mm/year (range, -0.88 - +0.64mm/year) in the vitamin E-blended group versus 0.133mm/year (range, -0.84 - +0.85mm/year) in the UHMWPE group (difference of medians 0.141, p=0.043).This study demonstrated that femoral head penetration was lower when using vitamin E-blended HXLPE when compared with UHMWPE, with a steady-state penetration rate far below the osteolysis threshold. Longer-term follow-up is needed to warrant whether wear reduction will generate less occurrence of osteolysis and aseptic loosening.

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