Le Mans, France
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Obert L.,Center Hospitalier Of Besancon | Ferrier M.,Center Hospitalier Of Besancon | Jacquot A.,Center Chirurgical lle | Mansat P.,Institut Universitaire de France | And 4 more authors.
Orthopaedics and Traumatology: Surgery and Research | Year: 2013

Introduction: Fractures of the distal humerus in patients over the age of 65 remain a therapeutic challenge. Treatment options include conservative treatment, internal fixation or total elbow arthroplasty. The complications of these different treatment options were evaluated in a multicentre study. Materials and methods: Four hundred and ninety-seven medical records were evaluated. A retrospective study was performed in 410 cases: 34 received conservative treatment, 289 internal fixation and 87 underwent total elbow arthroplasty. A prospective study was performed in 87 cases: 22 received conservative treatment, 53 internal fixation, and 12 underwent total elbow arthroplasty. Patients were evaluated after at least 6 months follow-up. Results: The rate of complications was 30% in the retrospective study and 29% in the prospective study. The rate of complications in the conservative treatment group was 60%, and the main complication was essentially malunion. The rate of complications was 44% in the internal fixation group and included neuropathies, mechanical failure or wound dehiscence. Although complications only developed in 23% of total elbow arthroplasties, they were often more severe than those following other treatments. Discussion: Complications develop in one out of three patients over 65 with distal humerus fractures. Three main types of complications were identified. Neuropathies especially of the ulnar nerve, especially during arthroplasty, must always be identified, the nerve requiring isolation and transposition. Bone complications, due principally to mechanical failure, were found following internal fixation. Despite technical progress, care must be taken not to favor excessive utilization of this treatment option in complex fractures on fragile bone. Although there were relatively fewer complications with total elbow arthroplasty they were more difficult to treat. Ossifications were frequent whatever the surgical option and can jeopardize the functional outcome. Level of evidence: Level IV. © 2013.


PubMed | Brest University Hospital Center, Unite de consultations externes, Nancy University Hospital Center, Institute Federatif Of Biologie and 21 more.
Type: Journal Article | Journal: European journal of human genetics : EJHG | Year: 2016

Heterozygous COL2A1 variants cause a wide spectrum of skeletal dysplasia termed type II collagenopathies. We assessed the impact of this gene in our French series. A decision tree was applied to select 136 probands (71 Stickler cases, 21 Spondyloepiphyseal dysplasia congenita cases, 11 Kniest dysplasia cases, and 34 other dysplasia cases) before molecular diagnosis by Sanger sequencing. We identified 66 different variants among the 71 positive patients. Among those patients, 18 belonged to multiplex families and 53 were sporadic. Most variants (38/44, 86%) were located in the triple helical domain of the collagen chain and glycine substitutions were mainly observed in severe phenotypes, whereas arginine to cysteine changes were more often encountered in moderate phenotypes. This series of skeletal dysplasia is one of the largest reported so far, adding 44 novel variants (15%) to published data. We have confirmed that about half of our Stickler patients (46%) carried a COL2A1 variant, and that the molecular spectrum was different across the phenotypes. To further address the question of genotype-phenotype correlation, we plan to screen our patients for other candidate genes using a targeted next-generation sequencing approach.


PubMed | Center hospitalier Le Mans, Service de rhumatologie, University Paris - Sud, Lille University Hospital Center and 2 more.
Type: Journal Article | Journal: RMD open | Year: 2016

Neurological manifestations seem common in primary Sjgrens syndrome (pSS) but their reported prevalences vary. We investigated the prevalence and epidemiology of neurological manifestations in a French nationwide multicentre prospective cohort of patients with pSS, the Assessment of Systemic Signs and Evolution in Sjgrens syndrome (ASSESS) cohort.The ASSESS cohort, established in 2006, includes 395 patients fulfilling American-European Consensus Group criteria for pSS. Demographic and clinical data were compared between patient groups with and without neurological manifestations, and across patient groups with peripheral nervous system (PNS) manifestations, central nervous system (CNS) manifestations and no neurological manifestations.Data at inclusion were available for 392 patients, whose mean age was 5812years. Mean follow-up was 33.9months. Neurological manifestations were present in 74/392 (18.9%) patients, including 63 (16%) with PNS manifestations and 14 (3.6%) with CNS manifestations. Prevalences were 9.2% for pure sensory neuropathy, 5.3% for sensorimotor neuropathy, 1.3% for cerebral vasculitis and 1.0% for myelitis. Neurological manifestations were associated with greater pSS activity as assessed using the ESSDAI (9.46.8 vs 4.34.8; p<0.001) and proportion of patients taking immunomodulatory/immunosuppressive drugs (32.4% (24/74) versus 13.8% (44/318), p=0003). New neurological symptoms were more common in patients with than without prior neurological manifestations (RR=3.918 (95% CI 1.91 to 8.05); p<0.001).Prevalences of peripheral and central neurological manifestations in pSS are about 15% and 5%, respectively. Neurological manifestations are associated with greater pSS activity. New neurological manifestations are more common in patients with prior neurological involvement.


Zalcman G.,University of Caen Lower Normandy | Zalcman G.,University Paris Diderot | Mazieres J.,Larrey Hospital | Margery J.,CNRS Gustave Roussy Institute | And 18 more authors.
The Lancet | Year: 2016

Background Malignant pleural mesothelioma is an aggressive cancer with poor prognosis, linked to occupational asbestos exposure. Vascular endothelial growth factor is a key mitogen for malignant pleural mesothelioma cells, therefore targeting of vascular endothelial growth factor might prove effective. We aimed to assess the effect on survival of bevacizumab when added to the present standard of care, cisplatin plus pemetrexed, as first-line treatment of advanced malignant pleural mesothelioma. Methods In this randomised, controlled, open-label, phase 3 trial, we recruited patients aged 18-75 years with unresectable malignant pleural mesothelioma who had not received previous chemotherapy, had an Eastern Cooperative Oncology Group performance status of 0-2, had no substantial cardiovascular comorbidity, were not amenable to curative surgery, had at least one evaluable (pleural effusion) or measurable (pleural tumour solid thickening) lesion with CT, and a life expectancy of >12 weeks from 73 hospitals in France. Exclusion criteria were presence of central nervous system metastases, use of antiaggregant treatments (aspirin ≥325 mg per day, clopidogrel, ticlopidine, or dipyridamole), anti-Vitamin K drugs at a curative dose, treatment with low-molecular-weight heparin at a curative dose, and treatment with non-steroidal anti-inflammatory drugs. We randomly allocated patients (1:1; minimisation method used [random factor of 0·8]; patients stratified by histology [epithelioid vs sarcomatoid or mixed histology subtypes], performance status score [0-1 vs 2], study centre, or smoking status [never smokers vs smokers]) to receive intravenously 500 mg/m2 pemetrexed plus 75 mg/m2 cisplatin with (PCB) or without (PC) 15 mg/kg bevacizumab in 21 day cycles for up to six cycles, until progression or toxic effects. The primary outcome was overall survival (OS) in the intention-to treat population. Treatment was open label. This IFCT-GFPC-0701 trial is registered with ClinicalTrials.gov, number NCT00651456. Findings From Feb 13, 2008, to Jan 5, 2014, we randomly assigned 448 patients to treatment (223 [50%] to PCB and 225 [50%] to PC). OS was significantly longer with PCB (median 18·8 months [95% CI 15·9-22·6]) than with PC (16·1 months [14·0-17·9]; hazard ratio 0·77 [0·62-0·95]; p=0·0167). Overall, 158 (71%) of 222 patients given PCB and 139 (62%) of 224 patients given PC had grade 3-4 adverse events. We noted more grade 3 or higher hypertension (51 [23%] of 222 vs 0) and thrombotic events (13 [6%] of 222 vs 2 [1%] of 224) with PCB than with PC. Interpretation Addition of bevacizumab to pemetrexed plus cisplatin significantly improved OS in malignant pleural mesothelioma at the cost of expected manageable toxic effects, therefore it should be considered as a suitable treatment for the disease. Funding Intergroupe Francophone de Cancérologie Thoracique (IFCT). © 2016 Elsevier Ltd.


Cavailles A.,Nantes University Hospital Center | Brinchault-Rabin G.,Hopital Pontchaillou | Dixmier A.,CHR dOrleans | Goupil F.,Center Hospitalier Le Mans | And 9 more authors.
European Respiratory Review | Year: 2013

By 2020, chronic obstructive pulmonary disease (COPD) will be the third cause of mortality. Extrapulmonary comorbidities influence the prognosis of patients with COPD. Tobacco smoking is a common risk factor for many comorbidities, including coronary heart disease, heart failure and lung cancer. Comorbidities such as pulmonary artery disease and malnutrition are directly caused by COPD, whereas others, such as systemic venous thromboembolism, anxiety, depression, osteoporosis, obesity, metabolic syndrome, diabetes, sleep disturbance and anaemia, have no evident physiopathological relationship with COPD. The common ground between most of these extrapulmonary manifestations is chronic systemic inflammation. All of these diseases potentiate the morbidity of COPD, leading to increased hospitalisations and healthcare costs. They can frequently cause death, independently of respiratory failure. Comorbidities make the management of COPD difficult and need to be evaluated and treated adequately. © ERS 2013.


Laribi K.,Center Hospitalier Le Mans | Denizon N.,Center Hospitalier Le Mans | Ghnaya H.,Center Hospitalier Le Mans | Atlassi M.,Center Hospitalier Le Mans | And 4 more authors.
European Journal of Haematology | Year: 2014

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy which was first included as an independent cutaneous lymphoma in the 2008 World Health Organisation (WHO) classification (1). BPDCN usually has an extremely poor prognosis, with quick relapses after chemotherapy (2; 3). Here, we report two cases of patients diagnosed in 2011 with BPDCN and myelodysplasia, and who were treated for the first time with 5-azacytidine (5-Aza); a drug approved by the Food and Drug Administration (FDA) and mainly used in the treatment of myelodysplastic syndrome (Kaminskas E, et al. 2005 Clin Cancer Res, 11, 3604-8). The first case was an 81-year-old man who presented with unusual CD10+, CD56- immunohistochemistry and 45X, -Y abnormality using fluorescent in situ hybridization (FISH) analysis. The second case was a 78-year-old woman who manifested monosomy 13 and chromosome instability due to D13S319 locus deletion in 13q14 as determined by FISH. Both patients showed excellent responses of their skin lesions after one cycle of chemotherapy, and their hematological disease was stabilized; however, pulmonary sepsis set in, followed by neutropenia after the fourth and the fifth cycle of treatment, that is, eight and 9 months postdiagnosis, respectively, leading to patient death. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


DesbEne C.,Center Hospitalier le Mans | Gaillard O.,Center Hospitalier le Mans
Annales de Biologie Clinique | Year: 2014

This paper points out the structural and physiological data of galectin-3, and emphasizes its role in cardiac fibrosis and heart failure pathophysiology. Then we summarize the optimal conditions for sampling, assays and we discuss the interpretation of results.


AIM : To calculate the prevalence of emmetropia, myopia, hyperopia, and amblyopia. METHOD : Cross sectional, descriptive, populationbased study, studying 212 randomly selected Lebanese patients of Armenian origin, aged from 15 to 45 years, from June 1 st till September 30 th 2003. The patients presenting with no exclusion factors are examined, before and after cycloplegia. Mean keratometry and mean ocular axial length are measured for each eye. RESULTS : 212 patients are examined. Mean age is 33.6 years. Sexe ratio F/M is 1.94. The prevalence of hyperopia, emmetropia and myopia is 14.6%, 51%, and 34.4% before cycloplegia, and 50%, 16.5% and 33.5% after cycloplegia, respectively. 14.9% of patients wearing myopic corrections were not found myopic after cycloplegia. The prevalence of amblyopia is 19.8%. Most of hyperopic patients do not wear eye-glasses (p = 0.00000101), whereas most of the myopic patients wear eyeglasses (p = 0.00000024). CONCLUSION : Prevalence of hyperopia is very high (50%) in this group of Lebanese Armenian population, as well as amblyopia (19.8%). Moreover, 6.7% of myopic patients wearing eyeglasses are not truly myopic.


Introduction: Telephone counseling is a daily occurrence in the pediatric emergency department (ED). It is difficult and has no legal framework. In 2010, we created a new protocol aimed at improving the telephone counseling given by the admission nurse at our pediatric emergency department: an index card is created for every call, color-coded according to severity with a list of clinical items, allowing for simple and reproducible advice. Materials and methods: The aim of this study was to evaluate the reliability of the cards. We conducted a prospective analysis, from June 2011 to January 2012, to analyze every card generated for seven major reasons for calling. The study was designed to: (a) measure the level of accurate completion of the cards by the admission nurse; (b) evaluate the quality of the advice given, as defined by the color coding. Results: Of 3297 calls received, 1033 cards were included in the analysis: 504 (49%) of these cards were correctly completed for optimal traceability (complete administrative and clinical data, correct color coding). The level of completion significantly increased for admission nurses who had filled in more than ten cards. Among these 504 calls, 386 cards (77%) delivered appropriate advice and 87 (17%) inappropriate advice. Thirty-one cards (6%) could not be evaluated for the quality of the advice given. There was no significant difference between the different causes for calling.Overall, only ten calls (less than 2%) resulted in underestimation of the severity of the child's condition, and 9% in overestimation (leading to an unnecessary consultation in the ED). Discussion: The quality of card completion needs to improve, especially since this study demonstrates how easy it is to use these cards. They ensure exhaustive questioning; guide the admission nurse toward safer advice, with appropriate advice given in 77% of cases. The rate of underestimated severity is low, and the initial severity of these cases is debatable because half of these cases consulted at the ED 12-24. h after the initial call. Conclusion: These innovative color-coded cards make it possible to dispense reliable and harmonized advice. They ease the process of an otherwise difficult exercise. © 2013.


Some non-small cell lung cancers harbor single mutated oncogenes that, as EGFR mutation or ALK fusion genes, are valid predictors of increased sensitivity to specific inhibitors. Molecular subsets have been recently identified and are potential targets for new therapies. Thus, besides these two mutations, those illustrate the therapeutic relevance of molecular clusters, a lot of genomic alterations, belonging to the proteins of the MAPK family - as BRAF or MEK1 - or to the proteins of the PI3K signaling - as PI3KCA or AKT-have been found in lung tumors. However, because of the molecular complexity of NSCLC, the way from the identification of driver mutations to substantial therapeutic improvements will be certainly long. KRAS mutations are the most commonly mutated oncogenes and are essentially negative predictors of benefit from adjuvant chemotherapy or anti- EGFR therapy; inversely, no direct RAS inhibitors have proven clinically effective. Squamous-cell lung cancer do not benefit from these advances in targeted therapeutics, but the discovery of genome alterations, as amplifications of FGFR1 or mutations of the DDR2 gene, can be the first step for development of distinct molecularly therapeutics. © 2012 Elsevier Masson SAS.

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