Dubuquoy L.,French Institute of Health and Medical Research |
Colombel J.-F.,Icahn Medical School |
Jouret-Mourin A.,Cliniques Universitaires |
Delos M.,CHU UCL Mont Godinne |
And 5 more authors.
Inflammatory Bowel Diseases | Year: 2013
Background: Increased lymphatic vessel (LV) density has been found in uninflamed intestinal wall of patients with Crohn's disease (CD). The goal of the study was to search for an association between LV density in the proximal ileal resection margin at the time of surgery and endoscopic recurrence. Methods: Ileocolonic resection specimens were obtained from 28 CD patients and 10 control subjects. The ileal proximal uninflamed section was used for the histological quantification of LV using immunohistochemistry with D2-40 antibody in the mucosa and submucosa. Quantification of LV was performed in 8 consecutive fields and was blinded to recurrence score. Patients were divided into 2 groups based on the presence (Rutgeerts score, i3/i4) (R+) or absence (Rutgeerts score, i0/i1) (R-) of endoscopic recurrence 1 year after the surgery. All patients were free of immunomodulators or biologics between surgery and postoperative endoscopy. Results: Median LV density was lower in control subjects than in CD patients in the mucosa (4.5%; interquartile range [IQR], 3.6-5.3 versus 5.9%; IQR, 4.2-8.5; P = 0.04) and submucosa (2.4%; IQR, 1.9-3.6 versus 5.7%; IQR, 4.3-6.9; P < 0.01). R-patients had a higher LV density in the proximal resection margin at surgery than R+ patients, both in the mucosa (8.5%; IQR, 6.5-10.3 versus 4.4%; IQR, 3.1-6.1; P < 0.01) and in the submucosa (6.3%; IQR, 5.5-9.3 versus 5.3%; IQR, 3.4-5.9; P = 0.03). Mucosal LV density greater than 7% predicted the absence of endoscopic recurrence at 1 year, with a sensitivity of 81% and a specificity of 75%. Conclusions: Decreased LV density is associated with high risk of endoscopic recurrence after surgery. Therapies that improve lymphatic flow in the gut may reduce the incidence of endoscopic recurrence. Copyright © 2013 Crohn's & Colitis Foundation of America, Inc.
Feagan B.,University of Western Ontario |
Colombel J.-F.,CHRU Lille |
Sandborn W.J.,University of California at San Diego |
Reinisch W.,University of Vienna |
And 7 more authors.
Gastroenterology | Year: 2012
Treatment of inflammatory bowel disease has greatly improved with the development of targeted, monoclonal antibody-based therapies. Tumor necrosis factor antagonists are frequently used to treat patients with Crohn's disease or ulcerative colitis, but they have side effects and their efficacy often decreases with use. New, more effective drugs are therefore needed and in development. However, many agents that appeared to be promising in preclinical studies have failed to show efficacy in clinical trials. We discuss possible reasons for the failures of these reagents in trials, which include the high rate of response to placebo, an inadequate range of doses, inappropriate timing of end point measurements, the changing therapeutic environment, and the competitive trial system. We also review regulatory guidelines for end points and trial design and recommend ways to improve trials. © 2012 AGA Institute.
PubMed | Clermont Ferrand University Hospital, Montpellier University, University of Nantes, Necker Hospital and 22 more.
Type: | Journal: Bone marrow transplantation | Year: 2017
Allogeneic stem cell transplantation (allo-SCT) following a non-myeloablative (NMA) or reduced-intensity conditioning (RIC) is considered a valid approach to treat patients with refractory/relapsed Hodgkin lymphoma (HL). When an HLA-matched donor is lacking a graft from a familial haploidentical (HAPLO) donor, a mismatched unrelated donor (MMUD) or cord blood (CB) might be considered. In this retrospective study, we compared the outcome of patients with HL undergoing a RIC or NMA allo-SCT from HAPLO, MMUD or CB. Ninety-eight patients were included. Median follow-up was 31 months for the whole cohort. All patients in the HAPLO group (N=34) received a T-cell replete allo-SCT after a NMA (FLU-CY-TBI, N=31, 91%) or a RIC (N=3, 9%) followed by post-transplant cyclophosphamide. After adjustment for significant covariates, MMUD and CB were associated with significantly lower GvHD-free relapse-free survival (GRFS; hazard ratio (HR)=2.02, P=0.03 and HR=2.43, P=0.009, respectively) compared with HAPLO donors. In conclusion, higher GRFS was observed in Hodgkin lymphoma patients receiving a RIC or NMA allo-SCT with post-transplant cyclophosphamide from HAPLO donors. Our findings suggest they should be favoured over MMUD and CB in this setting.Bone Marrow Transplantation advance online publication, 9 January 2017; doi:10.1038/bmt.2016.349.
PubMed | Besancon University Hospital Center, CHU Tours, University of Nantes, Limoges University Hospital Center and 16 more.
Type: | Journal: Transplant international : official journal of the European Society for Organ Transplantation | Year: 2017
Kidney transplantation is one of the therapeutic options for end-stage renal disease (ESRD) in systemic sclerosis (SS). Current evidence demonstrates poorer patient and graft survival after transplantation in SS than in other primary kidney diseases. All the patients presenting ESRD associated with SS who had received a kidney allograft between 1987 and 2013 were systematically included from 20 French kidney transplantation centres. Thirty-four patients received 36 kidney transplants during the study period.. Initial kidney disease was scleroderma renal crisis in 76.4%. Extra-renal involvement of SS was generally stable, excepted cardiac and gastro intestinal involvements, which worsened after kidney transplantation in 45% and 26% of cases respectively. Patient survival was 100%, 90.3% and 82.5% at 1, 3, and 5 years post transplant respectively. Pulmonary involvement of SS was an independent risk factor of death after transplantation. Death-censored graft survival was 97.2% after 1 and 3 years, and 92.8% after 5 years. Recurrence of scleroderma renal crisis was diagnosed in 3 cases. In our study, patient and graft survivals after kidney transplantation can be considered as excellent. On this basis, we propose that in the absence of extra-renal contraindication, SS patients presenting with ESRD should be considered for kidney transplantation. This article is protected by copyright. All rights reserved.
Fantoni-Quinton S.,CHRU Lille |
Frimat P.,Lille 2 University of Health and Law
Sante Publique | Year: 2011
Sante Emploi Info Service (Health and Employment Information Service) is a regional information service aimed at providing support and assistance to people who are struggling to perform their job effectively or to return to work as a result of a health problem. Through personalized assistance and follow-up, the service aims to help individuals to avoid professional exclusion, to provide accessible information, and to encourage networking between healthcare professionals and services specializing in job retention and vocational rehabilitation. In total, 1,392 calls have been received since the service opened in 2006, with most calls dealing with employment, income and legal matters and a range of psychological counseling issues. More than half of the proposed solutions have proved successful. The regional service (a unique initiative in France) is supported by Lille Regional Hospital and helps individuals suffering from health problems to overcome obstacles to job retention and vocational rehabilitation. The service also provides specifically-tailored information about legal procedures relating to professional integration and vocational rehabilitation.
Karila L.,University Paris - Sud |
Megarbane B.,French Institute of Health and Medical Research |
Megarbane B.,University of Paris Descartes |
Megarbane B.,University Paris Diderot |
And 2 more authors.
Current Neuropharmacology | Year: 2015
New psychoactive substances (NPS) have completely modified the drug scene and the current landscape of addiction. Synthetic substances, such as substituted or synthetic cathinones, also known as « legal highs », are often produced and used to mimic the effects of controlled drugs such as cocaine, methylenedioxymethamphetamine (MDMA, ecstasy), and methamphetamine. The overwhelming majority of synthetic cathinones are produced in China and South East Asian countries. The Internet has emerged as the new marketplace for NPS, playing a major role in providing information on acquisition, synthesis, extraction, identification, and substance use. All these compounds are intentionally mislabeled and sold on-line under slang terms such as bath salts, plant food, plant feeders and research chemicals. They are sometimes labeled « not for human use » or « not tested for hazards or toxicity ». The rapid spread of NPS forces member countries of the European Union to adapt their response to the potential new dangers that may cause. To date, not only health actors but also the general public need to be clearly informed and aware of dangers resulting from NPS spread and use. Here, we review the major clinical effects of synthetic cathinones to highlight their impact on public health. A literature search was conducted from 2009 to 2014 based on PubMed, Google Scholar, Erowid, and governmental websites, using the following keywords alone or in combination: “new psychoactive substances”, “synthetic cathinones”, “substituted cathinones”, “mephedrone”, “methylone”, “MDPV”, “4-MEC”, “addiction”, and “substance use disorder”. © 2015 Bentham Science Publishers.
Dubuquoy L.,French Institute of Health and Medical Research |
Dubuquoy L.,Lille University of Science and Technology |
Louvet A.,French Institute of Health and Medical Research |
Louvet A.,Lille University of Science and Technology |
And 21 more authors.
Gut | Year: 2015
Objective In alcoholic hepatitis (AH), development of targeted therapies is crucial and requires improved knowledge of cellular and molecular drivers in liver dysfunction. The unique opportunity of using explanted livers from patients with AH having undergone salvage liver transplantation allowed to perform more in-depth molecular translational studies. Design We studied liver explants from patients with AH submitted to salvage transplantation (n=16), from patients with alcoholic cirrhosis without AH (n=12) and fragments of normal livers (n=16). Hepatic cytokine content was quantified. Hepatocyte function and proliferation and the presence of hepatic progenitor cells (HPCs) were evaluated by immunohistochemistry, western blot or quantitative PCR. Mitochondrial morphology was evaluated by electron microscopy. Results Livers from patients with AH showed decreased cytokine levels involved in liver regeneration (tumour necrosis factor α and interleukin-6), as well as a virtual absence of markers of hepatocyte proliferation compared with alcoholic cirrhosis and normal livers. Electron microscopy revealed obvious mitochondrial abnormalities in AH hepatocytes. Importantly, livers from patients with AH showed substantial accumulation of HPCs that, unexpectedly, differentiate only into biliary cells. AH livers predominantly express laminin (extracellular matrix protein favouring cholangiocyte differentiation); consequently, HPC expansion is inefficient at yielding mature hepatocytes. Conclusions AH not responding to medical therapy is associated with lack of expression of cytokines involved in liver regeneration and profound mitochondrial damage along with lack of proliferative hepatocytes. Expansion of HPCs is inefficient to yield mature hepatocytes. Manoeuvres aimed at promoting differentiation of HPCs into mature hepatocytes should be tested in AH.
Bergeron-Lafaurie A.,CHRU Lille
Revue des Maladies Respiratoires Actualites | Year: 2011
The aging lung is a natural phenomenon characterized by a progressive loss of lung repair structures. This results from several mechanisms among them immunosenescence, increased oxidative stress and apoptosis alterations. Immunosenescence is responsible for increased morbidity and mortality in multiple respiratory areas: bacterial and viral infections, asthma, COPD. Immunosenescence is not expressed homogeneously: in some diseases the adaptive immunity is mainly depressed while the innate immunity can be very amplifled. This lack of immunity is reinforced over the years by malnutrition and certain co-morbidities. Immunosenescence must lead us to reconsider our therapeutic approach in the elderly: «new» vaccines, «cytokine therapy», anti-oxidant supplementation.... © 2011 Société de Pneumologie de Langue Française (SPLF).
Lemyze M.,Schaffner Hospital |
Mallat J.,Schaffner Hospital |
Duhamel A.,CHRU Lille |
Pepy F.,Schaffner Hospital |
And 5 more authors.
Critical Care Medicine | Year: 2013
OBJECTIVE: To evaluate the extent to which sitting position and applied positive end-expiratory pressure improve respiratory mechanics of severely obese patients under mechanical ventilation. DESIGN: Prospective cohort study. SETTINGS: A 15-bed ICU of a tertiary hospital. PARTICIPANTS: Fifteen consecutive critically ill patients with a body mass index (the weight in kilograms divided by the square of the height in meters) above 35 were compared to 15 controls with body mass index less than 30. INTERVENTIONS: Respiratory mechanics was first assessed in the supine position, at zero end-expiratory pressure, and then at positive end-expiratory pressure set at the level of auto-positive endexpiratory pressure. Second, all measures were repeated in the sitting position. MEASUREMENTS AND MAIN RESULTS: Assessment of respiratory mechanics included plateau pressure, auto-positive end-expiratory pressure, and flow-limited volume during manual compression of the abdomen, expressed as percentage of tidal volume to evaluate expiratory flow limitation. In supine position at zero end-expiratory pressure, all critically ill obese patients demonstrated expiratory flow limitation (flow-limited volume, 59.4% [51.3-81.4%] vs 0% [0-0%] in controls; p < 0.0001) and greater auto-positive end-expiratory pressure (10 [5-12.5] vs 0.7 [0.4-1.25] cm H2O in controls; p < 0.0001). Applied positive end-expiratory pressure reverses expiratory flow limitation (flow-limited volume, 0% [0-21%] vs 59.4% [51-81.4%] at zero end-expiratory pressure; p < 0.001) in almost all the obese patients, without increasing plateau pressure (24 [19-25] vs 22 [18-24] cm H2O at zero end-expiratory pressure; p = 0.94). Sitting position not only reverses partially or completely expiratory flow limitation at zero end-expiratory pressure (flow-limited volume, 0% [0-58%] vs 59.4% [51-81.4%] in supine obese patients; p < 0.001) but also results in a significant drop in auto-positive end-expiratory pressure (1.2 [0.6-4] vs 10 [5-12.5] cm H2O in supine obese patients; p < 0.001) and plateau pressure (15.6 [14-17] vs 22 [18-24] cm H2O in supine obese patients; p < 0.001). CONCLUSIONS: In critically ill obese patients under mechanical ventilation, sitting position constantly and significantly relieved expiratory flow limitation and auto-positive end-expiratory pressure resulting in a dramatic drop in alveolar pressures. Combining sitting position and applied positive end-expiratory pressure provides the best strategy. Copyright © 2013 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins.
PubMed | Marseille University Hospital Center, Nouvelles Cliniques Nantaises, Nancy University Hospital Center, Clinique Pasteur and 10 more.
Type: | Journal: Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology | Year: 2017
The magnitude of benefit related to implantable cardioverter defibrillator (ICD) therapy for primary prevention of sudden cardiac death (SCD) in non-ischaemic cardiomyopathy (NICM) and ischaemic cardiomyopathy (ICM) has not been evaluated extensively in clinical practice.Of the 5539 consecutive patients enrolled in the multicentre Dfibrillateur Automatique Implantable-Prvention Primaire (DAI-PP) study (2002-12), 5485 patients (with information on underlying heart disease) were included in the present analysis: 2181 (39.8%) had NICM and 3304 (60.2%) had ICM. ICM patients were older (63.710.3 vs. 60.612.2 years, P<0.0001), with a higher ejection fraction [27% (25-30) vs. 25% (20-30), P<0.0001], narrower QRS (37.3% vs. 21.4% with QRS<120, P<0.0001), and higher prevalence of sinus rhythm (77.3% vs. 74.0%, P=0.009). During a mean follow-up of 3.12.2 years, 814 patients died, giving a mortality incidence of 48.6 per 1000 person-years [95% confidence interval (CI) 45.2-51.9], higher among ICM patients (52.3, 95% CI 47.8-56.7) than in NICM patients (42.4, 95% CI 37.3-47.6; P=0.008) (adjusted hazard ratio 1.31, 95% CI 1.06-1.61, P=0.01). The increase in mortality among ICM patients was mainly due to non-cardiovascular mortality (P=0.0002), whereas incidences of cardiovascular mortality (including ICD-unresponsive SCD) were similar in the two groups. Incidences of appropriate ICD interventions (anti-tachycardia pacing, shocks) were similar, but inappropriate therapies were more frequent in NICM (7.94 vs. 5.96%; P=0.005).NICM and ICM patients had a same rate of ICD therapy for primary prevention of SCD in everyday practice. But, ICM patients more often died of a non- cardiovascular cause of death.NCT 01992458.