Fouret R.,Telecom ParisTech |
Laffaire J.,Programme Carte dIdentite des Tumeurs |
Hofman P.,Nice University Hospital Center |
Beau-Faller M.,CHU Strasbourg |
And 10 more authors.
Clinical Cancer Research | Year: 2012
Purpose: To identify genetic changes that could drive cancer pathogenesis in never and ever smokers with lung adenocarcinoma. Experimental Design: We analyzed the copy number and gene expression profiles of lung adenocarcinomas in 165 patients and related the alterations to smoking status. Having found differences in the tumor profiles, we integrated copy number and gene expression data from 80 paired samples. Results: Amplifications at 8q24.12 overlapping MYC and ATAD2 were more frequent in ever smokers. Unsupervised analysis of gene expression revealed two groups: in the group with mainly never smokers, the tumors expressed genes common to normal lung; in the group with more ever smokers, the tumors expressed "proliferative" and "invasive" gene clusters. Integration of copy number and gene expression data identified one module enriched in mitotic genes and MYC targets. Its main associated modulator was ATAD2, a cofactor of MYC. A strong dose-response relationship between ATAD2 and proliferation-related gene expression was noted in both never and ever smokers, which was verified in two independent cohorts. Both ATAD2 and MYC expression correlated with 8q24.12 amplification and were higher in ever smokers. However, only ATAD2, and not MYC, overexpression explained the behavior of proliferation-related genes and predicted a worse prognosis independently of disease stage in a large validation cohort. Conclusions: The likely driving force behind MYC contribution to uncontrolled cell proliferation in lung adenocarcinoma is ATAD2. Deregulation of ATAD2 is mainly related to gene amplification and is more frequent in ever smokers. ©2012 AACR.
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.
Chaze T.,Institute for Radiological Protection and Nuclear Safety |
Slomianny M.-C.,Lille University of Science and Technology |
Milliat F.,Institute for Radiological Protection and Nuclear Safety |
Tarlet G.,Institute for Radiological Protection and Nuclear Safety |
And 6 more authors.
Molecular and Cellular Proteomics | Year: 2013
Exposure of the skin to ionizing radiation leads to characteristic reactions that will often turn into a pathophysiological process called the cutaneous radiation syndrome. The study of this disorder is crucial to finding diagnostic and prognostic bioindicators of local radiation exposure or radiation effects. It is known that irradiation alters the serum proteome content and potentially post-translationally modifies serum proteins. In this study, we investigated whether localized irradiation of the skin alters the serum glycome. Two-dimensional differential in-gel electrophoresis of serum proteins from a man and from mice exposed to ionizing radiation showed that potential post-translational modification changes occurred following irradiation. Using a large-scale quantitative mass-spectrometry-based glycomic approach, we performed a global analysis of glycan structures of serum proteins from non-irradiated and locally irradiated mice exposed to high doses of γ-rays (20, 40, and 80 Gy). Non-supervised descriptive statistical analyses (principal component analysis) using quantitative glycan structure data allowed us to discriminate between uninjured/slightly injured animals and animals that developed severe lesions. Decisional statistics showed that several glycan families were down-regulated whereas others increased, and that particular structures were statistically significantly changed in the serum of locally irradiated mice. The observed increases in multiantennary N-glycans and in outer branch fucosylation and sialylation were associated with the up-regulation of genes involved in glycosylation in the liver, which is the main producer of serum proteins, and with an increase in the key proinflammatory serum cytokines IL-1β, IL-6, and TNFα, which can regulate the expression of glycosylation genes. Our results suggest for the first time a role of serum protein glycosylation in response to irradiation. These protein-associated glycan structure changes might signal radiation exposure or effects. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.
Martinaud C.,Federation de Biologie Clinique |
Ausset S.,Hopital DInstruction des Armees Percy |
Deshayes A.V.,Sanguine |
Cauet A.,Hopital DInstruction des Armees Percy |
And 2 more authors.
Journal of Trauma - Injury, Infection and Critical Care | Year: 2011
Background: Modern warfare causes severe injuries, and despite rapid transportation to theater regional trauma centers, casualties frequently arrive coagulopathic and in shock. Massive hemorrhage management includes transfusion of red blood cells and plasma in a 1:1 ratio. Fresh frozen plasma requires thawing and badly fits the emergency criteria. Since 1994, the French Military Blood Bank has been producing freeze-dried plasma (FDP) and providing it for overseas operation. The aim of our study was to evaluate the use of FDP in war settings and to assess its clinical efficiency and safety. PATIENTS: We performed a prospective study of the FDP delivered at the International Security Assistance Force Role 3 Military Medical Treatment Facility in the Kabul Afghanistan International Airport between February 2010 and February 2011. We included every patient who received at least one unit of FDP. Basic clinical data were recorded at admission. Transfusion requirements were monitored. Biological testing were performed before and after administration of FDP including hemoglobin concentration, platelets count, fibrinogen level, prothrombin time (PT), and thromboelastography. Result: Eighty-seven casualties received FDP during 93 episodes of transfusion. On average, 3.5 FDP units were transfused per episodes of transfusion. Of the 87 patients studied, 7 died because of nonsurvivable injuries and outcomes were unavailable for 11. The other 59 patients survived. PT significantly declined by an average of 3.3 seconds after FDP transfusion. This moderate decrease in PT reflects continued bleeding and resuscitation. It nevertheless suggests improvement in hemostasis before surgical control of bleeding. All FDP users reported ease of use, clinically observed efficacy equivalent to fresh frozen plasma and the absence of adverse effects associated with FDP. CONCLUSION: Our results provide evidence of the effectiveness of FDP for the prevention or correction of coagulopathy and hemorrhage in combat casualties.Copyright © 2011 by Lippincott Williams & Wilkins.
Falzone E.,Hopital dInstruction des Armees Percy |
Hoffmann C.,Hopital dInstruction des Armees Percy |
Keita H.,University Paris Diderot
Drugs and Aging | Year: 2013
Elderly people represent the fastest-growing segment of our society and undergo surgery more frequently than other age groups. Effective postoperative analgesia is essential in these patients because inadequate pain control after surgery is associated with adverse outcomes in elderly patients. However, management of postoperative pain in older patients may be complicated by a number of factors, including a higher risk of age- and disease-related changes in physiology and disease-drug and drug-drug interactions. Physiological changes related to aging need to be carefully considered because aging is individualized and progressive. Assessment of pain management needs to include chronological age, biological age with regard to renal, liver and cardiac functions, and the individual profile of pathology and prescribed medications. In addition, ways in which pain should be assessed, particularly in patients with cognitive impairment, must be considered. Cognitively intact older patients can use most commonly used unidimensional pain scales such as the visual analogue scale (VAS), verbal rating scale (VRS), numeric rating scale (NRS) and facial pain scale (FPS). VRS and NRS are the most appropriate pain scales for the elderly. In older patients with mild to moderate cognitive impairment, the VRS is a better tool. For severe cognitively impaired older patients, behavioural scales validated in the postoperative context, such as Doloplus-2 or Algoplus, are appropriate. For postoperative pain treatment, most drugs (e.g. paracetamol, nonsteroidal anti-inflammatory drugs, nefopam, tramadol, codeine, morphine, local anaesthetics), techniques (e.g. intravenous morphine titration, subcutaneous morphine, intravenous or epidural patient-controlled analgesia, intrathecal morphine, peripheral nerve block) and strategies (e.g. anticipated intraoperative analgesia or multimodal analgesia) used for acute pain management can be used in older patients. However, in view of pharmacokinetic and pharmacodynamic changes in older persons, the higher incidence of co-morbidities and concurrent use of other drugs, each must be carefully adjusted to suit each patient. Evaluation of treatment efficacy and incidence and severity of adverse events should be monitored closely, and the concept of 'start low and go slow' should be adopted for most analgesic strategies. © 2012 Springer International Publishing Switzerland.
Daudin M.,Hopital dinstruction des armees Percy |
Defontaine D.,Hopital dinstruction des armees Percy
Annales Medico-Psychologiques | Year: 2015
Through the clinical story of a gendarme confronted with several successive traumatic events, on the occasion of violent riots in Ivory Coast, then later, in Île-de-France, the authors wish to illustrate the relevance of a joint care by the psychiatrist and the psychomotor therapist within the framework of the psychic trauma. This patient, whose physical integrity was repeatedly threatened, presents, beyond the initial experience of peritraumatic dissociation, a state of post-traumatic stress coming along with a progressive loss of the identical marks. The complementary action of the psychiatrist and the psychomotor therapist allows the joint of a direct, concrete work, on the involvement of the body and the work of word. The psychotherapeutic care attempts to build of the sense and to put in words the traumatic experience. The contribution of the psychomotricity is complementary: she allows the patient, by means of the body, to return to the "sensory", but by giving him the possibility of a putting in act and a putting in words. The work made in psychotherapy finds its continuation in psychomotricity, and vice versa. © 2015 Elsevier Masson SAS.
[Amputation in low-income countries: particularities in epidmiological features and management practices]. [Les amputations dans les pays à faibles revenus: particularités de l'épidémiologie, de l'appareillage et de la rééducation.]
Bisseriex H.,Hopital dInstruction des Armees Percy
Médecine tropicale : revue du Corps de santé colonial | Year: 2011
The epidemiological features and management practices associated with amputation in low-income countries, generally synonymous with the tropics, are different from those observed in Western countries. Unlike developed countries, amputation most frequently involves traumatic injury in young active people. However, Westernization of the lifestyle is leading to an increasing number of cases involving diabetes and atherosclerotic disease. In the developing world, leprosy and Buruli ulcer are still significant etiologic factors for amputation. In war-torn countries, use of antipersonnel landmines is another major cause of amputation with characteristic features. Management of amputees in the developing world is hindered by the lack of facilities for rehabilitation and prosthetic fitting. Many international organizations are supporting national programs to develop such facilities. In addition to being affordable, prosthetics and orthotics must be adapted to the living conditions of a mostly rural amputee population, i.e., heat, humidity, and farm work. The rehabilitation process must be part of a global handicap policy aimed at changing attitudes about disability and reintegrating amputees both socially and professionally.
Three individual psychotherapies offered in psychotraumatology: Between opposition and suppositions on specific and/or common action mechanisms [Trois psychothérapies individuelles proposées en psychotraumatologie: Entre oppositions et suppositions de mécanismes d'action spécifiques et/ou communs?]
Auxemery Y.,Hopital dinstruction des armees Percy
Annales Medico-Psychologiques | Year: 2016
Which psychotherapy(ies) for psychotraumatised subjects? Today is referenced hundreds of psychotherapeutic approaches that hold many differences! Different theories and psychotherapeutic techniques contribute to what is common to assemble under the same term of "psychotherapy" practices based on an interpersonal relationship to cure illnesses, to resolve a disorder, to appease maladjustment or suffering. We will present the most common cares offered by psychotraumatology: the cognitive and behavioral psychotherapy (CBT), Eye Movement Desensitization and Reprocessing (EMDR) and psychodynamic psychotherapies before discussing their mechanisms of action. If "schools" sometimes sell contradictory practices, in fact, common principles and techniques are actually shared by three psychotherapeutic orientations. © 2015.
Bouix J.,Hopital dInstruction des Armees Percy
Oxymag | Year: 2013
Continuous professional development is the new programme which will govern the continuous education of all health care professionals. It will become fully operational during the course of 2013. It encourages interprofessional coherence as well as the coordination of national or regional plans. The composition of the CPD programmes combines the analysis of practices and the perfecting of skills.
Coutier D.,Hopital dinstruction des armees Percy
Annales Medico-Psychologiques | Year: 2015
In August 2013, in the acme of the Syrian crisis, the French State decides on the implementation of a medical surgical structure bound for the Syrian refugees, positioned within the camp of Za'atari in Jordan, a few kilometers away from the Syrian border. In front of the obvious fact of the psychic wounds of this bruised, saddened population and in exile, the medicopsychologic urgency will override the surgical aspect, so the device will evolve allowing the implementation of a binomial psychiatrist/psychologist. The operation "Tamour" is atypical because it places the action of the Health service for the benefit of the refugees in the center of its mission, and not in its kingly mission of support of the armed forces. The psychological problems of the Syrian refugees are in direct link with the related traumatic experiences of the civil war horrors (torture, rape, executions, bombing raids), but also with the insecurity and violence of life in the long course on a refugee camp of more than 140,000 people. We will also develop the particular work with children through mediations, distinct from the support for adults. Finally, particular attention will be paid on the experience of the military detachment, disarmed and without enemy, dispossessed of their warrior ideal, risking a difficult identification with the exiles statute of Syrian refugees. © 2015.