Author: "Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL]" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL]"' showing total 160 results

Start Over Author "Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL]"

160 results on '"Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL]"'

1. Risk profile, quality of life and care of patients with moderate and advanced CKD : The French CKD-REIN Cohort Study

Author: Sophie Liabeuf, Ziad A. Massy, Bénédicte Stengel, Bruce M. Robinson, Jean-François Deleuze, Christophe Pascal, L. Frimat, Maurice Laville, Joost P. Schanstra, Serge Briançon, Marie Metzger, Karine Legrand, Carole Ayav, Céline Lange, Pascal Morel, Denis Fouque, Christian Combe, Elodie Speyer, Christian Jacquelinet, Yves-Edouard Herpe, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Bioingénierie tissulaire (BIOTIS), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Agence de la biomédecine [Saint-Denis la Plaine], Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Réseau Lorrain de prise en charge de l’insuffisance rénale chronique : Réseau NEPHROLOR (Nephrolor), Service de néphrologie, Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université Jean Moulin - Lyon 3 (UJML), Université de Lyon, Biobanque de Picardie [CHU Amiens - Hôpital Sud], CHU Amiens-Picardie, Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Equipe 7 Inserm U1048, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Arbor Research Collaborative for Health, Service Néphrologie/Dialyse [AP-HP Ambroise-Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Département de Néphrologie, Université Bordeaux Segalen - Bordeaux 2, Centre d'Investigation Clinique - Epidemiologie Clinique/essais Cliniques Nancy, Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Réseau Lorrain de prise en charge de l’insuffisance rénale chronique : Réseau NEPHROLOR ( Nephrolor ), Hospices Civils de Lyon ( HCL ) -Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ), Maladies chroniques, santé perçue, et processus d'adaptation. Approches épidémiologiques et psychologiques. ( APEMAC - EA 4360 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Transfert de gènes dans le foie : applications thérapeutiques, Université Paris-Sud - Paris 11 ( UP11 ) -IFR93-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire des sciences et techniques de l'information, de la communication et de la connaissance ( Lab-STICC ), École Nationale d'Ingénieurs de Brest ( ENIB ) -Université de Bretagne Sud ( UBS ) -Université de Brest ( UBO ) -Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques ( IBNM ), Université de Brest ( UBO ) -Université européenne de Bretagne ( UEB ) -ENSTA Bretagne-Institut Mines-Télécom [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Centre National de Génotypage ( CNG ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Institut de médecine moléculaire de Rangueil ( I2MR ), Université Paul Sabatier - Toulouse 3 ( UPS ) -IFR31-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'Epidémiologie et Evaluations Cliniques [CHRU Nancy] ( Pôle S2R ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Centre de Recherche Clinique, Centre hospitalier universitaire d'Amiens ( CHU Amiens-Picardie ), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT), Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Chronic Kidney Disease - Réseau Epidémiologie et Information en Néphrologie (CKD REIN), Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Nephrology, medicine.medical_specialty, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Renal function, Blood Pressure, 030204 cardiovascular system & hematology, urologic and male genital diseases, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Interquartile range, Internal medicine, Diabetes Mellitus, medicine, Albuminuria, Humans, Patient Reported Outcome Measures, Prospective Studies, Prospective cohort study, [ SHS.GESTION ] Humanities and Social Sciences/Business administration, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, Transplantation, business.industry, Acute Kidney Injury, Middle Aged, Prognosis, medicine.disease, female genital diseases and pregnancy complications, 3. Good health, Proteinuria, Cardiovascular Diseases, Cohort, Quality of Life, Kidney Failure, Chronic, [SHS.GESTION]Humanities and Social Sciences/Business administration, Female, France, medicine.symptom, business, Glomerular Filtration Rate, Cohort study, Kidney disease
Abstract: International audience; Background: The French Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort study was designed to investigate the determinants of prognosis and care of patients referred to nephrologists with moderate and advanced chronic kidney disease (CKD). We examined their baseline risk profile and experience.Methods: We collected bioclinical and patient-reported information from 3033 outpatients with CKD and estimated glomerular filtration rates (eGFRs) of 15-60 mL/min/1.73 m2 treated at 40 nationally representative public and private facilities.Results: The patients' median age was 69 (60-76) years, 65% were men, their mean eGFR was 33 mL/min/1.73 m2, 43% had diabetes, 24% had a history of acute kidney injury (AKI) and 57% had uncontrolled blood pressure (BP; >140/90 mmHg). Men had worse risk profiles than women and were more likely to be past or current smokers (73% versus 34%) and have cardiovascular disease (59% versus 42%), albuminuria >30 mg/mmol (or proteinuria > 50) (40% versus 30%) (all P < 0.001) and a higher median risk of end-stage renal disease within 5 years, predicted by the kidney failure risk equation {12% [interquartile range (IQR) 3-37%] versus 9% [3-31%], P = 0.008}. During the previous year, 60% of patients reported one-to-two nephrologist visits and four or more general practitioner visits; only 25% saw a dietician and 75% were prescribed five or more medications daily. Physical and mental quality of life (QoL) were poor, with scores
Published: 2018

2. Management of upper gastrointestinal bleeding in emergency departments, from bleeding symptoms to diagnosis: a prospective, multicenter, observational study

Author: Dominique Pateron, François-Xavier Ageron, Laurent Jacquin, Pierre-Alexis Raynal, Jacques-Emmanuel Galimard, Sébastien Beaune, Pierre-Clément Thiebaud, Youri Yordanov, Service des Urgences [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Initiatives de Recherche aux Urgences [Paris, France], Société Française de Médecine d'Urgence [Paris, France], Sorbonne Universités, Université Pierre et Marie Curie - Paris 6 (UPMC), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), Equipe 2 : ECSTRA - Epidémiologie Clinique, STatistique, pour la Recherche en Santé (CRESS - U1153), Université Paris Diderot - Paris 7 (UPD7)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), Service des Urgences [AP-HP Hôpital Ambroise-Paré], AP-HP Hôpital Ambroise-Paré [Boulogne-Billancourt], Service des Urgences [Hôpital Edouard Herriot - Hospices Civils de Lyon], Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Service des Urgences [Metz-Tessy], Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], This study did not receive any specific funding., Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Sorbonne Université (SU), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Ambroise Paré [AP-HP], Service d'Urgences Adultes [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), BMC, BMC, Initiatives de Recherche aux Urgences Group, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Université Pierre et Marie Curie - Paris 6 ( UPMC ), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité ( CRESS (U1153 / UMR_A 1125) ), Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA ), Equipe 2 : ECSTRA - Epidémiologie Clinique, STatistique, pour la Recherche en Santé ( CRESS - U1153 ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité ( CRESS (U1153 / UMR_A 1125) ), Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA ), Hospices Civils de Lyon ( HCL ) -Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Adult, Male, medicine.medical_specialty, Gastrointestinal bleeding, [SDV]Life Sciences [q-bio], Critical Care and Intensive Care Medicine, 03 medical and health sciences, 0302 clinical medicine, Melena, Intensive care, Epidemiology, medicine, Humans, 030212 general & internal medicine, Prospective Studies, Original Research, Aged, Aged, 80 and over, [ SDV ] Life Sciences [q-bio], medicine.diagnostic_test, business.industry, Emergency department, lcsh:Medical emergencies. Critical care. Intensive care. First aid, Emergency Service, Hospital, Endoscopy, Female, France, Gastrointestinal Hemorrhage/diagnosis, Gastrointestinal Hemorrhage/etiology, Gastrointestinal Hemorrhage/therapy, Middle Aged, Symptom Assessment, Hematemesis, lcsh:RC86-88.9, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Emergency medicine, Emergency Medicine, Portal hypertension, 030211 gastroenterology & hepatology, Upper gastrointestinal bleeding, medicine.symptom, business, Gastrointestinal Hemorrhage
Abstract: Background Upper gastrointestinal bleeding (UGB) is common in emergency departments (EDs) and can be caused by many eso-gastro-duodenal lesions. Most available epidemiological data and data on the management of UGB comes from specialized departments (intensive care units or gastroenterology departments), but little is known from the ED perspective. We aimed to determine the distribution of symptoms revealing UGB in EDs and the hemorrhagic lesions identified by endoscopy. We also describe the characteristics of patients consulting for UGB, UGB management in the ED and patients outcomes. Method This was a prospective, observational, multicenter study covering 4 consecutive days in November 2013. Participating EDs were part of the Initiatives de Recherche aux Urgences network coordinated by the French Society of Emergency Medicine. All patients with suspected UGB in these EDs were included. Results In total, 110 EDs participated, including 194 patients with suspected UGB (median age 66 years [Q1-Q3: 51-81]). Overall, 104 patients (54%) had hematemesis and 75 (39%) melena. Endoscopy revealed lesions in 121 patients, mainly gastroduodenal ulcer or ulcerations (41%) or bleeding lesions due to portal hypertension (20%). The final diagnosis of UGB was reversed by endoscopy in only 3% of cases. Overall, 67 patients (35%) had at least one severity sign. Twenty-one patients died (11%); 40 (21%) were hospitalized in intensive care units and 126 (65%) in medicine departments; 28 (14%) were outpatients. Mortality was higher among patients with clinical and biological severity signs. Conclusion Most of the UGB cases in EDs are revealed by hematemesis. The emergency physician diagnosis of UGB is rarely challenged by the endoscopic findings. Electronic supplementary material The online version of this article (doi:10.1186/s13049-017-0425-6) contains supplementary material, which is available to authorized users.
Published: 2016

3. Influenza vaccine effectiveness among adult patients in a University of Lyon hospital (2004–2009)

Author: Brigitte Coppéré, Bruno Lina, Sélilah Amour, Corinne Régis, Brigitte Comte, Philippe Vanhems, Nicolas Voirin, M. Bouscambert-Duchamp, Silène Pires-Cronenberger, Laboratoire de Biométrie et Biologie Evolutive ( LBBE ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique ( Inria ) -Centre National de la Recherche Scientifique ( CNRS ), Service d'Hygiène, Epidémiologie et Prévention [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Virologie et pathologie humaine ( VirPath ), Université de Lyon-Université de Lyon, Service de médecine gériatrique, Hospices Civils de Lyon ( HCL ) -Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Virologie et pathologie humaine (VirPath), Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], and Hospices Civils de Lyon (HCL)
Subjects: Male, Hospitalized patients, [SDV]Life Sciences [q-bio], MESH : Aged, MESH : Prospective Studies, Hospitals, University, MESH: Influenza Vaccines, MESH: Aged, 80 and over, 0302 clinical medicine, Medicine, MESH : Female, Prospective Studies, MESH : Influenza, Human, 030212 general & internal medicine, Aged, 80 and over, MESH: Aged, 0303 health sciences, MESH: Middle Aged, MESH: Influenza, Human, virus diseases, Middle Aged, MESH : Adult, MESH: Case-Control Studies, 3. Good health, Infectious Diseases, Influenza Vaccines, Molecular Medicine, Female, France, Adult, MESH : Case-Control Studies, medicine.medical_specialty, Influenza vaccine, MESH : Male, Virus, 03 medical and health sciences, Age groups, Internal medicine, Influenza, Human, Flu season, Humans, MESH : Middle Aged, MESH : France, MESH : Aged, 80 and over, MESH : Hospitals, University, Aged, 030304 developmental biology, MESH: Hospitals, University, MESH: Humans, [ SDV ] Life Sciences [q-bio], General Veterinary, General Immunology and Microbiology, Adult patients, business.industry, MESH : Humans, Public Health, Environmental and Occupational Health, MESH: Adult, MESH: Male, MESH: Prospective Studies, MESH : Influenza Vaccines, Confidence interval, MESH: France, Case-Control Studies, Immunology, business, MESH: Female
Abstract: International audience; The aim of this study was to estimate influenza vaccine effectiveness (IVE) against laboratory-confirmed influenza among hospitalized patients. A case-control investigation was based on the prospective surveillance of influenza-like illness (ILI) during five flu seasons. We compared influenza-positive cases and influenza-negative controls. Unadjusted overall IVE was 62% (95% confidence interval 24% to 81%). We found that IVE was lower during the 2004-05 flu season (11%; 95% CI -232% to 76%) when the vaccine and circulating viruses were mismatched. Expansion of the study to other hospitals could provide IVE estimates earlier in the season, for different age groups and emerging virus strains.
Published: 2012

4. Aberrant DNA methylation distinguishes hepatocellular carcinoma associated with HBV and HCV infection and alcohol intake

Author: Fabien Zoulim, Marie-Pierre Lambert, Massimo Tommasino, Zdenko Herceg, Jörg Tost, Jean-Yves Scoazec, Anupam Paliwal, Pierre Hainaut, Thomas Vaissière, Bakary S. Sylla, Isabelle Chemin, Centre de Recherche en Cancérologie de Lyon (CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Interactions Bactéries-Cellules (UIBC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Institut National de la Recherche Agronomique (INRA), International Agency for Cancer Research (IACR), Equipe 16, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Service d'hépatologie et de gastroentérologie, Hospices Civils de Lyon (HCL)-Hôtel-Dieu-Hospices Civils de Lyon (HCL)-Hôtel-Dieu-Centre de Recherche en Cancérologie de Lyon (CRCL), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Sect Mech Carcinogenesis, equipe 4, Laboratoire Central d'Anatomie et de Cytologie Pathologiques [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Centre de Recherche en Cancérologie de Lyon (CRCL), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Interactions Bactéries-Cellules ( UIBC ), Institut National de la Recherche Agronomique ( INRA ) -Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), International Agency for Cancer Research ( IACR ), International Agency for Cancer Research, Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Hospices Civils de Lyon ( HCL ) -Hôtel-Dieu-Hospices Civils de Lyon ( HCL ) -Hôtel-Dieu-Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer ( CIRC - IARC ), Organisation mondiale de la santé (OMS/WHO), international Agency for Research on Cancer - IARC, Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ) -Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ) -Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre National de Génotypage ( CNG ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Hospices Civils de Lyon (HCL)-Hôtel-Dieu-Hospices Civils de Lyon (HCL)-Hôtel-Dieu-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), and Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, MESH : Liver Neoplasms, MESH : Aged, Receptors, Nicotinic, MESH: Base Sequence, medicine.disease_cause, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: DNA Methylation, 0302 clinical medicine, Risk Factors, MESH: Liver Neoplasms, MESH: Risk Factors, MESH : Female, MESH: Gene Silencing, MESH: Carcinoma, Hepatocellular, MESH: Glutathione S-Transferase pi, MESH: Aged, 0303 health sciences, MESH: Middle Aged, MESH : Tumor Suppressor Proteins, Liver Neoplasms, RNA-Binding Proteins, DNA, Neoplasm, Hepatitis C, Methylation, Middle Aged, MESH : Adult, Hepatitis B, MESH : Risk Factors, 3. Good health, DNA-Binding Proteins, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, DNA methylation, MESH: Receptors, Nicotinic, Female, MESH : DNA Primers, MESH : DNA, Neoplasm, MESH : DNA-Binding Proteins, Adult, MESH : Carcinoma, Hepatocellular, MESH: DNA Primers, Carcinoma, Hepatocellular, Alcohol Drinking, MESH : Male, Hepatitis C virus, MESH : RNA-Binding Proteins, MESH: DNA, Neoplasm, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, MESH: Phosphoproteins, 03 medical and health sciences, MESH : Gene Silencing, medicine, Humans, MESH : Middle Aged, MESH: Tumor Suppressor Proteins, Gene Silencing, neoplasms, Aged, DNA Primers, 030304 developmental biology, MESH: Hepatitis C, Hepatitis B virus, MESH: Humans, Base Sequence, MESH : Receptors, Nicotinic, MESH: Hepatitis B, Hepatology, Tumor Suppressor Proteins, MESH : Humans, MESH : Hepatitis B, Cancer, MESH: Adult, DNA Methylation, MESH : Hepatitis C, Phosphoproteins, medicine.disease, MESH: Male, digestive system diseases, MESH : Alcohol Drinking, MESH: RNA-Binding Proteins, Glutathione S-Transferase pi, MESH : Glutathione S-Transferase pi, Immunology, MESH : Base Sequence, MESH : Phosphoproteins, MESH : DNA Methylation, MESH: Female, MESH: Alcohol Drinking, MESH: DNA-Binding Proteins
Abstract: International audience; BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is one of the most frequent human cancers and a major cause of cancer-related death worldwide. The major risk factors for developing HCC are infection by hepatitis B virus (HBV) and hepatitis C virus (HCV), chronic alcoholism, and aflatoxins; however, critical gene targets remain largely unknown. Herein, we sought to establish DNA methylation patterns in HCC and corresponding cirrhotic tissues and to identify DNA methylation changes associated with major risk factors. METHODS: We have established assays for quantitative analysis of DNA methylation levels in a panel of seven cancer-associated genes and repetitive elements, and combined these assays with a series of HCC tumors, associated with major risk factors, collected from two different geographical areas. RESULTS: We found a high frequency of aberrant hypermethylation of specific genes (RASSF1A, GSTP1, CHRNA3, and DOK1) in HCC tumors as compared to control cirrhotic or normal liver tissues, suggesting that aberrant hypermethylation exhibits non-random and tumor-specific patterns in HCC. Importantly, our analysis revealed an association between alcohol intake and the hypomethylation of MGMT and between hypermethylation of GSTP1 and HBV infection, indicating that hypermethylation of the genes analyzed in HCC tumors exhibits remarkably distinct patterns depending on associated risk factors. CONCLUSIONS: This study identifies aberrant DNA methylation of specific cellular genes in HCC and the major risk factors associated with these changes, providing information that could be exploited for biomarker discovery in clinics and molecular epidemiology.
Published: 2011

5. 18F-FLT and 18F-FDG positron emission tomography for the imaging of advanced well-differentiated gastro-entero-pancreatic endocrine tumours

Author: Francesco Giammarile, Valérie Hervieu, Didier Le Bars, Jean-Philippe Vuillez, Catherine Lombard-Bohas, Jean-Yves Scoazec, Catherine Cornu, Claire Houzard, Françoise Borson-Chazot, Claire Bournaud, Sandrine Masson, Thomas Walter, Marc Janier, Claire Billotey, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Laboratoire de Physico-Chimie des Matériaux Luminescents (LPCML), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, E04, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), DOCOMO Euro-Labs, DOCOMO Communications Laboratories Europe GmbH-DOCOMO Communications Laboratories Europe GmbH-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Université de Lyon, Laboratoire Central d'Anatomie et de Cytologie Pathologiques [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Radiopharmaceutiques biocliniques, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Evaluation et modélisation des effets thérapeutiques, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), CIC CHU Lyon (inserm), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), Laboratoire de Physico-Chimie des Matériaux Luminescents ( LPCML ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre d'Exploration et de Recherche Médicales par Émission de Positons ( CERMEP ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon ( HCL ) -CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), DOCOMO Communications Laboratories Europe GmbH-DOCOMO Communications Laboratories Europe GmbH-Centre de Recherche en Cancérologie de Lyon ( CRCL ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ) -Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ) -Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire de Biométrie et Biologie Evolutive ( LBBE ), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique ( Inria ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé ( CREATIS ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, MESH : Aged, Neuroendocrine tumors, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 030218 nuclear medicine & medical imaging, 0302 clinical medicine, MESH: Fluorodeoxyglucose F18, MESH : Intestinal Neoplasms, MESH : Stomach Neoplasms, MESH : Neoplasm Staging, MESH : Female, Prospective cohort study, MESH: Aged, MESH: Middle Aged, medicine.diagnostic_test, Ultrasound, MESH : Neuroendocrine Tumors, Cell Differentiation, MESH: Stomach Neoplasms, MESH: Neoplasm Staging, General Medicine, MESH : Adult, Middle Aged, MESH: Positron-Emission Tomography, 3. Good health, Neuroendocrine Tumors, MESH: Dideoxynucleosides, Positron emission tomography, 030220 oncology & carcinogenesis, MESH : Dideoxynucleosides, Female, MESH: Pancreatic Neoplasms, Radiology, MESH : Cell Differentiation, Preclinical imaging, MESH: Cell Differentiation, Adult, medicine.medical_specialty, MESH: Neuroendocrine Tumors, MESH : Male, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Fluorodeoxyglucose F18, Stomach Neoplasms, Intestinal Neoplasms, Brain positron emission tomography, medicine, Humans, Endocrine system, MESH : Middle Aged, Radiology, Nuclear Medicine and imaging, MESH: Intestinal Neoplasms, Aged, Neoplasm Staging, MESH: Humans, business.industry, MESH : Humans, MESH : Positron-Emission Tomography, MESH: Adult, MESH : Fluorodeoxyglucose F18, medicine.disease, MESH: Male, Dideoxynucleosides, Pancreatic Neoplasms, Positron-Emission Tomography, business, MESH: Female, MESH : Pancreatic Neoplasms, Progressive disease
Abstract: International audience; PURPOSE: Gastro-entero-pancreatic (GEP) endocrine tumours are a heterogenous group of tumours of variable localization and prognosis. It has been suggested that positron emission tomography (PET) using 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) may have a prognostic value and help to identify patients at risk of progression. [18F]fluoro-3'-deoxy-3'-L-fluorothymidine (18F-FLT) has been recently developed as a PET proliferation tracer. At present, there are no studies investigating its role in GEP. The aim of this prospective study was to assess the value of 18F-FLT-PET for the evaluation of GEP. MATERIALS AND METHODS: Ten patients with biopsy-proven locally advanced or metastasized, well-differentiated GEP neuroendocrine tumours were prospectively enrolled and scheduled for 18F-FDG and 18F-FLT-PET. Images were compared with other conventional diagnostic procedures, namely computed tomography, ultrasound, somatostatin receptor scintigraphy and with clinical and diagnostic follow-up. RESULTS: Evaluation criteria were interpreted in terms of assumed presence of tumoral tissue. According to the patient's status, FDG was positive in five out of the seven patients with stable disease and in two out of the three patients with progressive disease. No positive case was identified by 18F-FLT in either the primary or the metastatic tumour site, whatever the status of patients, and this was probably a reflection of the slow proliferation rate of tumours. CONCLUSION: These preliminary data suggest that 18F-FLT-PET is not a suitable tracer for the evaluation of advanced well-differentiated GEP tumours. FDG showed good diagnostic performance but does not help to identify patients at risk of progression.
Published: 2011

6. Incidence of cytomegalovirus infection in seropositive kidney transplant recipients treated with everolimus: A randomized, open-label, multicenter phase 4 trial

Author: Hannah Kaminski, Nassim Kamar, Olivier Thaunat, Nicolas Bouvier, Sophie Caillard, Isabelle Garrigue, Dany Anglicheau, Jean-Philippe Rérolle, Yannick Le Meur, Antoine Durrbach, Thomas Bachelet, Hélène Savel, Roxane Coueron, Jonathan Visentin, Arnaud Del Bello, Isabelle Pellegrin, Julie Déchanet-Merville, Pierre Merville, Rodolphe Thiébaut, Lionel Couzi, Service de Néphrologie Transplantation, Dialyse et Aphérèse [CHU Bordeaux], CHU Bordeaux [Bordeaux], Immunology from Concept and Experiments to Translation (ImmunoConcept), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Département de Néphrologie et Transplantation d'organes [CHU Toulouse], Pôle Urologie - Néphrologie - Dialyse - Transplantations - Brûlés - Chirurgie plastique - Explorations fonctionnelles et physiologiques [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Nephrology, Transplantation and Clinic Immunology [Hospices civils de Lyon], Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Service de Néphrologie-Dialyse-Transplantation rénale [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Néphrologie et Transplantation [Strasbourg], Hôpital Civil [Strasbourg], CHU Strasbourg-CHU Strasbourg, Virology Laboratory, Bordeaux University Hospital, Bordeaux, France, Service Néphrologie et transplantation rénale Adultes [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Néphrologie, Dialyse, Transplantations [CHU Limoges], CHU Limoges, Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHRU Brest - Service de Nephrologie (CHU - BREST - Nephrologie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hôpital Henri Mondor - Service de néphrologie et transplantation, Department of Nephrology, Transplantation and Dialysis, Bordeaux, France, Department of Nephrology, Transplantation and Dialysis, Bordeaux, Service d’information Médicale [CHU de Bordeaux] (Pôle de Santé Publique), Service d'immunologie et d'immunogénétique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Laboratoire d'immunologie et d'immunogénétique [CHU Bordeaux], Statistics In System biology and Translational Medicine (SISTM), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)- Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: T cell biology, Transplantation, immunosuppressant - mechanistic target of rapamycin: everolimus, clinical research, nephrology, virus diseases, kidney transplantation, [SDV.IMM]Life Sciences [q-bio]/Immunology, Immunology and Allergy, clinical trial, Pharmacology (medical), infection and infectious agents - viral: Cytomegalovirus (CMV), practice
Abstract: International audience; Cytomegalovirus (CMV) persists as the most frequent opportunistic infection among solid organ transplant recipients. This multicenter trial aimed to test whether treatment with everolimus (EVR) could decrease the incidence of CMV DNAemia and disease. We randomized 186 CMV seropositive kidney transplant recipients in a 1:1 ratio to receive EVR or mycophenolic acid (MPA) in association with basiliximab, cyclosporin, and steroids and 87 in each group were analyzed. No universal prophylaxis was administered to either group. The composite primary endpoint was the presence of CMV DNAemia, CMV treatment, graft loss, death, and discontinuation of the study at 6 months posttransplant. In the modified intent-to-treat analysis, 42 (48.3%) and 70 (80.5%) patients in the EVR and MPA groups reached the primary endpoint (OR = 0.21, 95% CI: 0.11-0.43, p
Published: 2022

7. MISE EN PLACE ET EVALUATION D'UNE ACTIVITE DE PHARMACIE CLINIQUE EN HOPITAL DE JOUR ONCOLOGIQUE

Author: Malagutti, Fiona, Faure, Rémi, Walter, Thomas, Forestier, Julien, Lombard-Bohas, Catherine, Pivot, Christine, service pharmaceutique Hôpital Edouard Herriot, Hospices Civils de Lyon, Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Faure, Rémi
Subjects: [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, [ SDV.SP ] Life Sciences [q-bio]/Pharmaceutical sciences, pharmacie clinique oncologique, chimiothérapies injectables, information patient, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences
Abstract: International audience; Introduction : En oncologie, la plupart des cures de chimiothérapie sont aujourd’hui administrées en hôpital de jour ce qui implique une autogestion adaptée des effets indésirables et un suivi pendant l’intercure au domicile du patient. L’objectif de cette étude est de contribuer à améliorer l’information au patient vis-à-vis de son traitement et de développer une activité de pharmacie clinique au sein d’un service d’oncologie.Matériel et méthodes : Des entretiens personnalisés d’information thérapeutique ont été mis en place pour les patients recevant une chimiothérapie injectable dans un service d’hôpital de jour d’oncologie médicale, en s’appuyant sur des plaquettes d’information spécifiques du protocole suivi par le patient. Parallèlement, nous avons effectué une anamnèse médicamenteuse du traitement complet de ces patients afin de réaliser un bilan pharmaco-thérapeutique dans le but de détecter d’éventuelles interactions médicamenteuses, et d’évaluer l’observance et l’automédication du patient vis-à-vis de son traitement habituel.Résultats : 50 entretiens patients ont été réalisé d’Avril à Septembre 2014. Nous avons pu constater que la consultation médicale n’était pas le moment le plus adapté pour la distribution de la plaquette et que seulement 16% (n=8) des patients avaient pu en bénéficier. Parmi les 42 patients sans plaquette, 64% (n=27) ignoraient la conduite à tenir en cas de survenue d’effets indésirables, contrairement à ceux qui l’avaient reçue, où 100% la connaissaient. L’évaluation de la plaquette a montré un excellent retour parmi les patients ayant bénéficié d’une 2e visite, avec de leur point de vue, une meilleure gestion du traitement pour eux même mais également pour leurs proches. 50% des interactions médicamenteuses détectées ont fait l’objet d’une intervention pharmaceutique (IP). 70% (n= 35) des patients présentaient au moins une interaction médicamenteuse.A propos de l’observance des patients, 16% (n=8) ont rapporté lors de l’entretien choisir librement, sans avis médical, de prendre ou non leurs traitements personnels. Quant à l’automédication, 68% (n=34) des patients déclarent prendre au moins un médicament en plus de leurs ordonnances.Discussion/conclusion : L’intégration du pharmacien hospitalier au sein des services de soins contribue à l’amélioration des connaissances du patient vis-à-vis de son traitement, en s’appuyant sur un support écrit spécifique à chaque protocole. Une présence pharmaceutique permet également de répondre aux interrogations des patients dans leur gestion de leurs traitements personnels, et favorise la détection des problèmes médicamenteux.
Published: 2015

8. IL-33 drives polyfunctionality and antitumor activity of a unique ST2+ NK cell population

Author: Treilleux, Isabelle, MICHALLET, MARIE-CECILE, Valladeau-Guilemond, Jenny, Marçais, Antoine, Walzer, Thierry, Krebs, Philippe, Cerwenka, Adelheid, Hubert, Margaux, Caux, Christophe, Bendriss-Vermare, Nathalie, Département de Biopathologie, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Réponse immunitaire innée dans les maladies infectieuses et auto-immunes – Innate immunity in infectious and autoimmune diseases, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Immunology and Microbial Science, The Scripps Research Institute [La Jolla, San Diego], German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Schering-Plough Laboratories for Immunological Research, and Schering Plough Laboratories
Subjects: cancer immunosurveillance, cancer immunotherapy, IL-33, ST2/IL1RL1, [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, NK cells, NK cells IL-33 ST2/IL1RL1 cancer immunosurveillance cancer immunotherapy, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity
Abstract: ARTICLE EN REVISION FAVORABLE DANS SCIENCE IMMUNOLOGY; Natural Killer (NK) cell subsets differ to ensure complementary and crucial roles in tumor immunosurveillance. Their biology is critically regulated by cytokines. Here, we show that IL-33 synergizes with IL-12 to strongly activate a subset of CD56 dim NK cells acquiring ST2 expression. Transcriptomic and biological analysis of human ST2 + CD56 dim NK cells revealed a distinct intermediate differentiation state between canonical CD56 bright and CD56 dim NK cells, combining high proliferative properties, cytokines/chemokines production, and cytotoxicity. NK cells expressing ST2 protein or exhibiting a ST2-linked transcriptional signature were identified in human and mouse tumors. Accordingly, IL-12 unleashes human breast tumor ST2 + NK cell potential to produce IFN-γ in response to IL-33 and IL-33/IL-12 co-injection resulted in a NK-dependent IFN- secretion and anti-tumor effects in murine mammary tumors. An IL33 hi-NK hi score in solid tumors correlated with increased progressionfree patient survival. Our findings thus identify polyfunctional ST2 + NK cells which effector functions can be harnessed by IL-33 to boost anti-tumor immunity.
Published: 2022

9. Immunohistochemical markers on needle biopsies are helpful for the diagnosis of focal nodular hyperplasia and hepatocellular adenoma subtypes

Author: François Paraf, Marie Christine Saint Paul, Saïd Taouji, Jeanne Ramos, Nathalie Sturm, Brigitte Bancel, Valérie Paradis, Dominique Wendum, Emmanuelle Leteurtre, Monique Fabre, Jean-Yves Scoazec, Paulette Bioulac-Sage, Charles Balabaud, Jessica Zucman-Rossi, Gaelle Cubel, Brigitte Le Bail, Sophie Michalak, Catherine Guettier, Jeanne Tran Van Nhieu, Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Fibrose hépatique et cancer du foie, Université Bordeaux Segalen - Bordeaux 2-IFR66-Institut National de la Santé et de la Recherche Médicale (INSERM), equipe 4, Laboratoire Central d'Anatomie et de Cytologie Pathologiques [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc - U837 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université Lille 2 - Faculté de Médecine, Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Albert Bonniot - Ontogénèse et oncogénèse moléculaires, CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'anatomie et cytologie pathologiques [CHU Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Equipe 16, Centre de Recherche en Cancérologie de Lyon (CRCL), Tumorothèque de Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Limoges (UNILIM), Hôpital Pasteur [Nice] (CHU), Laboratoire de Pathologie Cellulaire et Tissulaire, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Hôpital Paul Brousse, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse, Laboratoire d'anatomie pathologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Bordeaux Segalen - Bordeaux 2-IFR66-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ) -Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ) -Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de recherche Jean-Pierre Aubert-Neurosciences et Cancer, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lille, Droit et Santé, Centre de recherche biomédicale Bichat-Beaujon ( CRB3 ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHU Grenoble-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Service d'anatomie et cytologie pathologiques, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Université de Limoges ( UNILIM ), Hôpital Pasteur [Nice] ( CHU ), CHU Angers, Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse, Genomique Fonctionnelle des Tumeurs Solides, and Université Paris Diderot - Paris 7 ( UPD7 ) -IFR105-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: Core needle, Male, MESH: Biopsy, Large-Core Needle, Pathology, MESH : Liver Neoplasms, MESH: Focal Nodular Hyperplasia, MESH: beta Catenin, MESH : Hepatocytes, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Hepatocytes, MESH: Adenoma, Liver Cell, 0302 clinical medicine, MESH: Liver Neoplasms, MESH : Tumor Markers, Biological, MESH : Female, Hepatocyte Nuclear Factor 1-alpha, MESH : Algorithms, beta Catenin, medicine.diagnostic_test, Liver Neoplasms, Focal nodular hyperplasia, MESH : Adult, MESH : Biopsy, Large-Core Needle, MESH : Diagnosis, Differential, MESH: Predictive Value of Tests, 3. Good health, Focal Nodular Hyperplasia, 030220 oncology & carcinogenesis, Immunohistochemistry, 030211 gastroenterology & hepatology, MESH : Hepatocyte Nuclear Factor 1-alpha, Female, Anatomy, Algorithms, Adult, medicine.medical_specialty, MESH : Male, MESH: Algorithms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Pathology and Forensic Medicine, Adenoma, Liver Cell, Diagnosis, Differential, 03 medical and health sciences, MESH : Adenoma, Liver Cell, Glutamate-Ammonia Ligase, Predictive Value of Tests, MESH: Diagnosis, Differential, Biopsy, medicine, Biomarkers, Tumor, Humans, MESH: Glutamate-Ammonia Ligase, MESH : Predictive Value of Tests, MESH: Hepatocyte Nuclear Factor 1-alpha, MESH: Humans, business.industry, Significant difference, MESH : Humans, MESH: Adult, MESH : Glutamate-Ammonia Ligase, Hepatocellular adenoma, medicine.disease, MESH : beta Catenin, MESH: Male, Staining, MESH : Focal Nodular Hyperplasia, MESH: Tumor Markers, Biological, Hepatocytes, Surgery, Biopsy, Large-Core Needle, business, MESH: Female, Immunostaining
Abstract: International audience; Phenotypic identification of focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) subtypes using immunohistochemical markers has been developed from their molecular characteristics. Our objective was to evaluate the sensitivity of these markers in the definitive diagnosis of these lesions by core needle biopsies. A total of 239 needle biopsies paired with their surgical resection specimen (group A) or without an associated resection specimen (group B) were reviewed. Using a step-by-step algorithm after standard staining, appropriate immunostaining analyses were performed to determine the certainty of diagnosis of FNH, HNF1α-inactivated HCA, inflammatory HCA, β-catenin-activated HCA, or unclassified HCA. The diagnosis of FNH was certain or probable on routine stains in 53% of needle biopsies of group A, whereas after glutamine synthetase staining, the diagnosis was certain in 86.7% as compared with 100% on the corresponding surgical specimen (P=0.04). In needle biopsies of group A, the diagnosis of HCA was certain on routine stains in 58.6% as compared with 94.3% on surgical specimens. After specific immunostaining, diagnosis was established on biopsies with 74.3% certainty, including all HCA subtypes, with similar distribution in surgical specimens. For each "certain diagnosis" paired diagnostic test (biopsy and surgical specimen), a positive correlation was observed (P
Published: 2012

10. EMT Inducers Catalyze Malignant Transformation of Mammary Epithelial Cells and Drive Tumorigenesis towards Claudin-Low Tumors in Transgenic Mice

Author: Anne-Pierre Morel, Mojgan Devouassoux-Shisheboran, Alain Puisieux, Stéphane Ansieau, Frédérique Fauvet, Joël Lachuer, Douglas B. Spicer, Isabelle Treilleux, Anne Wierinckx, George W. Hinkal, Gareth J. Browne, Agnès Tissier, Baptiste Gras, Clémence Thomas, Isabelle Puisieux, Stéphanie Courtois-Cox, Julie Pourchet, equipe 2, Centre Léon Bérard [Lyon]-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-labex DEVweCAN, Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.)-Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), ProfileXpert, Université de Lyon-Université de Lyon-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-labex DEVweCAN, Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.)-Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.)-Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Biopathologie, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), equipe 11, department of cancer studies and molecular medicine, University of Leicester, centre for molecular medicine, Main medical center research institute, Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.)-Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.)-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Centre Léon Bérard [Lyon]-Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -labex DEVweCAN, Ministère de l'Éducation nationale, de l’Enseignement supérieur et de la Recherche ( M.E.N.E.S.R. ) -Ministère de l'Éducation nationale, de l’Enseignement supérieur et de la Recherche ( M.E.N.E.S.R. ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -labex DEVweCAN, Université de Lyon-Université de Lyon-Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -labex DEVweCAN, Ministère de l'Éducation nationale, de l’Enseignement supérieur et de la Recherche ( M.E.N.E.S.R. ) -Ministère de l'Éducation nationale, de l’Enseignement supérieur et de la Recherche ( M.E.N.E.S.R. ) -Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Léon Bérard [Lyon]-Hospices Civils de Lyon ( HCL ) -Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ), Institut Universitaire de France ( IUF ), Ministère de l'Éducation nationale, de l’Enseignement supérieur et de la Recherche ( M.E.N.E.S.R. ) -Ministère de l'Éducation nationale, de l’Enseignement supérieur et de la Recherche ( M.E.N.E.S.R. ) -Centre de Recherche en Cancérologie de Lyon ( CRCL ), and Ministère de l'Éducation nationale, de l’Enseignement supérieur et de la Recherche ( M.E.N.E.S.R. )
Subjects: Cancer Research, Cellular differentiation, medicine.disease_cause, Retinoblastoma Protein, Malignant transformation, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Twist transcription factor, Mice, 0302 clinical medicine, Protein Phosphatase 2, Telomerase, Genetics (clinical), 0303 health sciences, Malignant Conversion, Transdifferentiation, Cell Differentiation, Cell biology, Gene Expression Regulation, Neoplastic, Cell Transformation, Neoplastic, 030220 oncology & carcinogenesis, Medicine, Female, Research Article, Epithelial-Mesenchymal Transition, lcsh:QH426-470, Breast Neoplasms, Mice, Transgenic, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Cell Line, 03 medical and health sciences, Mammary Glands, Animal, Genetics, medicine, Animals, Humans, Neoplastic transformation, Epithelial–mesenchymal transition, Mammary Glands, Human, Molecular Biology, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Homeodomain Proteins, Twist-Related Protein 1, Zinc Finger E-box-Binding Homeobox 1, Epithelial Cells, lcsh:Genetics, Genes, ras, Claudins, Tumor Suppressor Protein p53, Carcinogenesis, Transcription Factors
Abstract: The epithelial-mesenchymal transition (EMT) is an embryonic transdifferentiation process consisting of conversion of polarized epithelial cells to motile mesenchymal ones. EMT–inducing transcription factors are aberrantly expressed in multiple tumor types and are known to favor the metastatic dissemination process. Supporting oncogenic activity within primary lesions, the TWIST and ZEB proteins can prevent cells from undergoing oncogene-induced senescence and apoptosis by abolishing both p53- and RB-dependent pathways. Here we show that they also downregulate PP2A phosphatase activity and efficiently cooperate with an oncogenic version of H-RAS in malignant transformation of human mammary epithelial cells. Thus, by down-regulating crucial tumor suppressor functions, EMT inducers make cells particularly prone to malignant conversion. Importantly, by analyzing transformed cells generated in vitro and by characterizing novel transgenic mouse models, we further demonstrate that cooperation between an EMT inducer and an active form of RAS is sufficient to trigger transformation of mammary epithelial cells into malignant cells exhibiting all the characteristic features of claudin-low tumors, including low expression of tight and adherens junction genes, EMT traits, and stem cell–like characteristics. Claudin-low tumors are believed to be the most primitive breast malignancies, having arisen through transformation of an early epithelial precursor with inherent stemness properties and metaplastic features. Challenging this prevailing view, we propose that these aggressive tumors arise from cells committed to luminal differentiation, through a process driven by EMT inducers and combining malignant transformation and transdifferentiation., Author Summary The epithelial-mesenchymal transition (EMT) is essential to germ layer formation and cell migration in the early vertebrate embryo. EMT is aberrantly reactivated under pathological conditions, including fibrotic disease and cancer progression. In the latter process, EMT is known to promote invasion and metastatic dissemination of tumor cells. EMT is orchestrated by a variety of embryonic transcription factors called EMT inducers. Among these, the TWIST and ZEB proteins are known to be frequently reactivated during tumor development. We here report in vitro and in vivo observations demonstrating that activation of these factors fosters cell transformation and primary tumor growth by alleviating key oncosuppressive mechanisms, thereby minimizing the number of events required for acquisition of malignant properties. In a model of breast cancer, cooperation between a single EMT inducer and a single mitogenic oncoprotein is sufficient to transform mammary epithelial cells into malignant cells and to drive the development of aggressive and undifferentiated tumors. Overall, these data underscore the oncogenic role of embryonic transcription factors in initiating the development of poor-prognosis neoplasms by promoting both cell transformation and dedifferentiation.
Published: 2012

11. Multidisciplinarity and medical decision, impact for patients with cancer: sociological assessment of two tumour committees' organization

Author: Pierre Meeus, Hervé Mignotte, Thomas Bachelot, Philippe Thiesse, Isabelle Treilleux, Marie-Pierre Sunyach, Perrine Marec-Berard, Jean-Yves Blay, Dominique Ranchère-Vince, Patrick Castel, Christelle Faure, Louis Tassy, A. Lurkin, Isabelle Ray-Coquard, Jean-Paul Guastalla, Nicole Guerin, Centre de sociologie des organisations (CSO), Sciences Po (Sciences Po)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], Eq 11, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Chirurgie cancérologique, Département d'anatomopathologie, biopathologie, Oncogénèse et progression tumorale, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Médecine Nucléaire, Department of Medical Oncology [Lyon], Eq 09, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biopathologie, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Service d'Imagerie, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Département de Biopathologie, Centre de sociologie des organisations (Sciences Po, CNRS) (CSO), and Scanella, Marie-Pierre
Subjects: Male, MESH: Decision Making, Cancer Research, Disease, Medical Oncology, MESH: Pathology, Clinical, Metastasis, MESH: Cancer Care Facilities, 0302 clinical medicine, MESH: Patient Care Team, Multidisciplinary approach, 030212 general & internal medicine, MESH: Advisory Committees, Disease management (health), MESH: Medical Oncology, Pathology, Clinical, [SHS.SOCIO]Humanities and Social Sciences/Sociology, Incidence (epidemiology), Sarcoma, Hematology, General Medicine, MESH: Radiation Oncology, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Medicine, Female, MESH: Interdisciplinary Communication, France, MESH: Radiology, Radiology, medicine.medical_specialty, Consensus, Advisory Committees, Decision Making, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cancer Care Facilities, 03 medical and health sciences, Breast cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, MESH: General Surgery, medicine, Humans, cancer, MESH: Group Structure, Radiology, Nuclear Medicine and imaging, MESH: Consensus, Patient Care Team, Gynecology, MESH: Humans, business.industry, Cancer, MESH: Medicine, medicine.disease, MESH: Male, approche multidisciplinaire, MESH: France, Group Structure, General Surgery, Family medicine, MESH: Sarcoma, Radiation Oncology, Interdisciplinary Communication, business, MESH: Female, MESH: Breast Neoplasms
Abstract: Purpose Medical practices in oncology are expected to be multidisciplinary, yet few articles studied how this may be concretely applied. In the present study, we evaluated the organization of two multidisciplinary committees, one for breast cancer and one for sarcoma, in a French Comprehensive Cancer Centre. Methods Both tumours were specifically chosen so as to emphasise substantial differences in relation with incidence, histological subtypes, management strategy, and scientific evidence. Between 2003 and 2004, 404 decision processes were observed, 210 for sarcoma (26 meetings) and 194 for breast cancer (10 meetings). The number of physicians who took part in the discussions and their medical specialties were systematically noted as well as the number of contradictory discussions, medical specialties represented in these contradictory discussions and the topics of contradiction. The last measured data was whether the final committee's decision was in conformity with the referent preferences or not. All these measures were related to the referent's medical speciality and working place, to the stage of the disease and to the disease management stage. Results Committees’ specificities concerned their organization, referent's medical specialties, the number of participants in discussions and their medical specialties. Discussions in the sarcoma committee tended to be more multidisciplinary, involving more specialties. Initial strategy proposal for one patient was modified during the discussions for 86 patients out of 210 (41%) and for 62 out of 194 (32%) respectively for sarcoma and breast cancer. However, there was no significant difference in the rate of contradictory discussions between breast cancer and sarcoma committees (32% versus 41% respectively; P = 0.08). The rates of contradictory discussions were similar for localized cancers, local relapse and metastasis disease (37%, 41% and 34% respectively; P = 0.86). Conclusions The present study reports more than 30% of changes concerning strategy for patient with cancer due to multidisciplinary discussions. This indicates that, providing tumour committees are adapted to the pathologies’ characteristics, they can promote a collective and multidisciplinary approach to oncology.
Published: 2012

12. Mutational characterization of individual breast tumors: TP53 and PI3K pathway genes are frequently and distinctively mutated in different subtypes

Author: Sandrine Boyault, Thomas Bachelot, Alain Puisieux, Christine Lasset, Claudine Navarro, Isabelle Treilleux, Youenn Drouet, Eric Tabone, Qing Wang, Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Equipe de prévention et épidémiologie génétique, Centre Léon Bérard [Lyon], Biologie Fonctionnelle, Insectes et Interactions (BF2I), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA), Luzhou Medical college, Department of spinal surgery, Eq 11, Oncogénèse et progression tumorale, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Cancérologie de Lyon (CRCL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Département de Médecine Nucléaire, Eq 09, Centre de Recherche en Cancérologie de Lyon (CRCL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Département de Biopathologie, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Eq 02, Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.)-Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.)-Centre de Recherche en Cancérologie de Lyon (CRCL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Département de Médecine Nucléaire, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Département de Biopathologie, Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.)-Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.)-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Genomique Fonctionnelle des Tumeurs Solides, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -IFR105-Université Paris Diderot - Paris 7 ( UPD7 ), Laboratoire de Biométrie et Biologie Evolutive ( LBBE ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique ( Inria ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Département de Médecine Nucléaire, Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Département de Biopathologie, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon ( HCL ) -Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ) -Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ), Biologie Fonctionnelle, Insectes et Interactions ( BF2I ), Institut National de la Recherche Agronomique ( INRA ) -Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Université de Lyon-Institut National des Sciences Appliquées ( INSA ), Institut Universitaire de France ( IUF ), Ministère de l'Éducation nationale, de l’Enseignement supérieur et de la Recherche ( M.E.N.E.S.R. ) -Ministère de l'Éducation nationale, de l’Enseignement supérieur et de la Recherche ( M.E.N.E.S.R. ) -Centre de Recherche en Cancérologie de Lyon ( CRCL ), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: MESH: Signal Transduction, Receptors, Steroid, Cancer Research, DNA Mutational Analysis, MESH : Aged, AKT1, Kaplan-Meier Estimate, MESH : PTEN Phosphohydrolase, MESH : Breast Neoplasms, Gene mutation, MESH: Cadherins, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, CDH1, Phosphatidylinositol 3-Kinases, 0302 clinical medicine, MESH: Carcinoma, Lobular, MESH : Female, MESH: DNA Mutational Analysis, MESH: Tumor Suppressor Protein p53, MESH: Genetic Association Studies, Genetics, MESH: Aged, 0303 health sciences, MESH: Middle Aged, Carcinoma, Ductal, Breast, MESH : Carcinoma, Lobular, Middle Aged, MESH : Adult, Cadherins, 3. Good health, MESH : Proto-Oncogene Proteins c-akt, Oncology, 030220 oncology & carcinogenesis, Female, MESH : Cadherins, Signal Transduction, Adult, Class I Phosphatidylinositol 3-Kinases, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH : DNA Mutational Analysis, Biology, MESH: PTEN Phosphohydrolase, MESH : Kaplan-Meier Estimate, 03 medical and health sciences, Breast cancer, Antigens, CD, medicine, Humans, PTEN, MESH : Middle Aged, Gene, Genetic Association Studies, PI3K/AKT/mTOR pathway, MESH: Kaplan-Meier Estimate, Aged, 030304 developmental biology, MESH : Signal Transduction, MESH: Humans, MESH: Proto-Oncogene Proteins c-akt, MESH : Humans, PTEN Phosphohydrolase, MESH : Carcinoma, Ductal, Breast, MESH : Phosphatidylinositol 3-Kinases, MESH: Adult, MESH : Genetic Association Studies, medicine.disease, MESH: Carcinoma, Ductal, Breast, Carcinoma, Lobular, MESH : Tumor Suppressor Protein p53, MESH: Phosphatidylinositol 3-Kinases, biology.protein, Tumor Suppressor Protein p53, Proto-Oncogene Proteins c-akt, MESH : Receptors, Steroid, MESH: Female, MESH: Breast Neoplasms, MESH: Receptors, Steroid
Abstract: International audience; Understanding how cancer genes are mutated in individual tumors is an important issue with potential clinical and therapeutic impact. This is especially relevant with recently developed targeted therapies since mutated genes can be targets and/or predictors. However, to date, gene mutation profiling in individual tumors is still underexplored. Breast cancer is composed of various subtypes. We presumed that this heterogeneity reflected the involvement of different molecular mechanisms including gene mutations that affect defined signaling pathways. Unlike the majority of published mutational studies, this study was aimed to draw a mutation profile in individual tumors by screening a panel of cancer genes in the same tumor. Thus, five genes frequently mutated in breast cancers: TP53, PIK3CA, PTEN, CDH1, and AKT1 were screened in each of 120 human primary breast tumors. Mutations in at least one of these genes were found in 62.5% of the tumors, of which the majority carried a single-gene mutation. Interestingly, a substantial proportion of tumors carried mutations either in TP53 or in genes of the PI3K pathway (PIK3CA or PTEN or AKT1). These two distinct mutation patterns were significantly associated to hormone receptor expression but independent of HER2 status.
Published: 2012

13. Influenza vaccination of healthcare workers in acute-care hospitals: a case-control study of its effect on hospital-acquired influenza among patients

Author: Bruno Lina, Corinne Régis, Brigitte Coppéré, Silene Cronenberger, Olivier Robert, Brigitte Comte, Philippe Vanhems, Nicolas Voirin, Thomas Bénet, Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon ( HCL ), Laboratoire de Biométrie et Biologie Evolutive ( LBBE ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique ( Inria ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Camille Jordan [Villeurbanne] ( ICJ ), École Centrale de Lyon ( ECL ), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Centre National de la Recherche Scientifique ( CNRS ), Virologie et pathologie humaine ( VirPath ), Université de Lyon-Université de Lyon, Service de médecine gériatrique, Hospices Civils de Lyon ( HCL ) -Hôpital Edouard Herriot [CHU - HCL], Service d'Hygiène, Epidémiologie et Prévention [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Hospices Civils de Lyon (HCL), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Institut Camille Jordan (ICJ), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), Virologie et pathologie humaine (VirPath), Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Institut Camille Jordan [Villeurbanne] (ICJ), Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, MESH : Orthomyxoviridae, [SDV]Life Sciences [q-bio], MESH : Aged, MESH : Prospective Studies, MESH: Influenza Vaccines, MESH: Aged, 80 and over, 0302 clinical medicine, Medical microbiology, Acute care, Health care, Medicine, MESH : Female, Prospective Studies, 030212 general & internal medicine, MESH : Influenza, Human, Prospective cohort study, MESH: Orthomyxoviridae, MESH: Aged, Aged, 80 and over, Cross Infection, 0303 health sciences, MESH: Middle Aged, biology, MESH: Influenza, Human, Vaccination, MESH: Nose, Healthcare worker, virus diseases, Middle Aged, MESH : Adult, MESH: Hospitals, Orthomyxoviridae, MESH: Case-Control Studies, Hospitals, 3. Good health, MESH : Hospitals, Infectious Diseases, MESH: Hemagglutination Inhibition Tests, Influenza Vaccines, Female, MESH : Nose, MESH : Cross Infection, Research Article, Adult, medicine.medical_specialty, MESH : Case-Control Studies, animal structures, Health Personnel, MESH : Male, education, Nose, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, Influenza, Human, Humans, lcsh:RC109-216, MESH : Middle Aged, MESH : Aged, 80 and over, Aged, MESH: Humans, [ SDV ] Life Sciences [q-bio], 030306 microbiology, business.industry, MESH : Humans, Case-control study, MESH: Cross Infection, MESH: Adult, MESH: Vaccination, Hemagglutination Inhibition Tests, biology.organism_classification, MESH: Male, MESH: Prospective Studies, MESH : Hemagglutination Inhibition Tests, MESH : Influenza Vaccines, MESH : Vaccination, Case-Control Studies, Immunology, Emergency medicine, MESH: Health Personnel, MESH : Health Personnel, business, MESH: Female
Abstract: Background In acute-care hospitals, no evidence of a protective effect of healthcare worker (HCW) vaccination on hospital-acquired influenza (HAI) in patients has been documented. Our study objective was to ascertain the effectiveness of influenza vaccination of HCW on HAI among patients. Methods A nested case-control investigation was implemented in a prospective surveillance study of influenza-like illness (ILI) in a tertiary acute-care university hospital. Cases were patients with virologically-confirmed influenza occurring ≥ 72 h after admission, and controls were patients with ILI presenting during hospitalisation with negative influenza results after nasal swab testing. Four controls per case, matched per influenza season (2004-05, 2005-06 and 2006-07), were randomly selected. Univariate and multivariate conditional logistic regression models were fitted to assess factors associated with HAI among patients. Results In total, among 55 patients analysed, 11 (20%) had laboratory-confirmed HAI. The median HCW vaccination rate in the units was 36%. The median proportion of vaccinated HCW in these units was 11.5% for cases vs. 36.1% for the controls (P = 0.11); 2 (20%) cases and 21 (48%) controls were vaccinated against influenza in the current season (P = 0.16). The proportion of ≥ 35% vaccinated HCW in short-stay units appeared to protect against HAI among patients (odds ratio = 0.07; 95% confidence interval 0.005-0.98), independently of patient age, influenza season and potential influenza source in the units. Conclusions Our observational study indicates a shielding effect of more than 35% of vaccinated HCW on HAI among patients in acute-care units. Investigations, such as controlled clinical trials, are needed to validate the benefits of HCW vaccination on HAI incidence in patients.
Published: 2012

14. Early detection of tumor cells by innate immune cells leads to T(reg) recruitment through CCL22 production by tumor cells

Author: Jean-Yves Blay, Thomas Bachelot, Isabelle Durand, Cathy Biota, Isabelle Treilleux, Michael Gobert, Sophie Léon-Goddard, Nadège Goutagny, Julien Faget, Christine Ménétrier-Caux, Christophe Caux, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Médecine Nucléaire, Centre Léon Bérard [Lyon], E09, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biopathologie, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), cytométrie, Oncogénèse et progression tumorale, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), E11, Equipe 11, Université de Lyon, Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Département de Biopathologie, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Cancérologie de Lyon (CRCL), and Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Cytotoxicity, Immunologic, Cancer Research, Interleukin-1beta, Cell Communication, Lymphocyte Activation, 0302 clinical medicine, MESH: Interleukin-1beta, IL-2 receptor, 0303 health sciences, Innate lymphoid cell, MESH: Gene Expression Regulation, Neoplastic, Acquired immune system, 3. Good health, Gene Expression Regulation, Neoplastic, Killer Cells, Natural, MESH: Leukocytes, Mononuclear, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Interleukin 12, Tumor necrosis factor alpha, Female, MESH: Immunity, Innate, MESH: Killer Cells, Natural, MESH: Cell Line, Tumor, MESH: Interferon-gamma, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, 03 medical and health sciences, Interferon-gamma, Immune system, Cell Line, Tumor, MESH: Cell Communication, medicine, Humans, MESH: Cytotoxicity, Immunologic, MESH: Lymphocyte Activation, 030304 developmental biology, Chemokine CCL22, Innate immune system, MESH: Humans, Tumor Necrosis Factor-alpha, Monocyte, MESH: Chemokine CCL22, Immunity, Innate, MESH: Tumor Necrosis Factor-alpha, Immunology, Leukocytes, Mononuclear, MESH: Female, MESH: Breast Neoplasms
Abstract: In breast carcinomas, patient survival seems to be negatively affected by the recruitment of regulatory T cells (Treg) within lymphoid aggregates by CCL22. However, the mechanisms underpinning this process, which may be of broader significance in solid tumors, have yet to be described. In this study, we determined how CCL22 production is controlled in tumor cells. In human breast carcinoma cell lines, CCL22 was secreted at low basal levels that were strongly increased in response to inflammatory signals [TNF-α, IFN-γ, and interleukin (IL)-1β], contrasting with CCL17. Primary breast tumors and CD45+ infiltrating immune cells appeared to cooperate in driving CCL22 secretion, as shown clearly in cocultures of breast tumor cell lines and peripheral blood mononuclear cells (PBMC) or their supernatants. We determined that monocyte-derived IL-1β and TNF-α are key players as monocyte depletion or neutralization of these cytokines attenuated secretion of CCL22. However, when purified monocytes were used, exogenous human IFN-γ was also required to generate this response suggesting a role for IFN-γ–producing cells within PBMCs. In this setting, we found that human IFN-γ could be replaced by the addition of (i) IL-2 or K562-activated natural killer (NK) cells or (ii) resting NK cells in the presence of anti-MHC class I antibody. Taken together, our results show a dialogue between NK and tumor cells leading to IFN-γ secretion, which in turn associates with monocyte-derived IL-1β and TNF-α to drive production of CCL22 by tumor cells and subsequent recruitment of Treg. As one validation of this conclusion in primary breast tumors, we showed that NK cells and macrophages tend to colocalize within tumors. In summary, our findings suggest that at early times during tumorigenesis, the detection of tumor cells by innate effectors (monocytes and NK cells) imposes a selection for CCL22 secretion that recruits Treg to evade this early antitumor immune response. Cancer Res; 71(19); 6143–52. ©2011 AACR.
Published: 2011

15. Quantitative and functional alterations of plasmacytoid dendritic cells contribute to immune tolerance in ovarian cancer

Author: Michael Gobert, Julien Faget, Alexandre Cassignol, Sana Intidhar Labidi-Galy, Nathalie Bendriss-Vermare, Jean-Yves Blay, Agathe Bajard, Christophe Caux, Vanja Sisirak, Isabelle Durand, Isabelle Treilleux, Jean-Damien Combes, François Mithieux, Olivier Tredan, Pierre Meeus, Isabelle Ray-Coquard, Christine Ménétrier-Caux, Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon, Centre Léon Bérard [Lyon], Service d'Oncologie Chirurgicale, Equipe 9, Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Département de Biopathologie, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Unité de Biostatistique et d'Evaluation des Thérapeutiques (UBET), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Applications des ultrasons à la thérapie, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Infirmerie protestante, Departement de chirurgie, Département de Médecine Nucléaire, Service d'Oncologie Médicale, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biopathologie
Subjects: Cancer Research, MESH: Immune Tolerance, MESH: Immunophenotyping, Enzyme-Linked Immunosorbent Assay, MESH: Flow Cytometry, [SDV.CAN]Life Sciences [q-bio]/Cancer, macromolecular substances, Biology, Immunophenotyping, Immune tolerance, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Immune system, MESH: Lymphocyte Culture Test, Mixed, Immune Tolerance, medicine, Humans, Macrophage, MESH: Cohort Studies, 030304 developmental biology, Ovarian Neoplasms, 0303 health sciences, Tumor microenvironment, MESH: Cytokines, MESH: Humans, MESH: Dendritic Cells, MESH: Enzyme-Linked Immunosorbent Assay, hemic and immune systems, Dendritic Cells, Dendritic cell, Flow Cytometry, medicine.disease, 3. Good health, MESH: Ovarian Neoplasms, Oncology, Immunology, Cytokines, Female, Interleukin-3 receptor, Lymphocyte Culture Test, Mixed, Ovarian cancer, MESH: Female, 030215 immunology
Abstract: In ovarian cancer, the immune system fails to eradicate established tumors partly due to the induction of immune tolerance within tumor microenvironment. In this study, we investigated the contribution of plasmacytoid dendritic cells (pDC) in the establishment of immune tolerance in a cohort of 44 ovarian cancer patients. In the tumor and malignant ascites, CD4+CD123+BDCA2+ pDC were the most abundant dendritic cell subset; however, they were profoundly depleted in peripheral blood. The presence of pDC in primary ovarian cancer, but not ascites, was an independent prognostic factor associated with early relapse. Following chemotherapy, we observed a partial restoration of blood pDC levels in patients in complete remission. These findings show preferential recruitment of pDC into tumors where they express a partially mature phenotype that may reflect an in situ activation. Importantly, compared with pDC found in ascites or blood, tumor-associated pDC (TApDC) produced less IFN-α, TNF-α, IL-6, macrophage inflammatory protein-1β, and RANTES in response to toll-like receptor stimulation, and alterations in pDC functions were mainly mediated through tumor-derived TNF-α and TGF-β. Unlike ascites-derived pDC, TApDC induced IL-10 production from allogeneic naive CD4+ T lymphocytes, suggesting the existence of a paracrine immunosuppressive loop. Taken together, our findings indicate that both local and systemic dysfunction of pDC play a critical role in the progression of ovarian cancer via induction of immune tolerance. Cancer Res; 71(16); 5423–34. ©2011 AACR.
Published: 2011

16. Under-estimation of self-reported occupational exposure by questionnaire in hospital workers

Author: Isabelle Pin, M.-A. Denis, N. Massin, F Kauffmann, C. Donnay, Dominique Choudat, Orianne Dumas, J. Fevotte, R. Magis, N. Le Moual, Service de Pneumologie Allergologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Médecine et Santé au Travail, Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Groupement Hospitalier Est, Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement (UMRESTTE UMR T9405), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR), Service Central de Médecine du Travail (SCMT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital de l'Hotel Dieu, Institut national de recherche et de sécurité (Vandoeuvre lès Nancy) (INRS ( Vandoeuvre lès Nancy)), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Merck Sharp & Dohme (MSD), Hospital program of clinical research (PHRC)-Paris, National Research Agency - Health environment, health-work program, French Agency of health safety, environment and work (AFSSET, EST-09-15)., CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Hospices Civils de Lyon ( HCL ) -Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Groupement Hospitalier Est, Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement ( UMRESTTE UMR T9405 ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux ( IFSTTAR ), Service Central de Médecine du Travail ( SCMT ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital de l'Hotel Dieu, Institut national de recherche et de sécurité (Vandoeuvre lès Nancy) ( INRS ( Vandoeuvre lès Nancy) ), Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut d'oncologie/développement Albert Bonniot de Grenoble ( INSERM U823 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), and Nadif, Rachel
Subjects: exposure assessment, MESH: Asthma, MESH : Aged, MESH: Self Disclosure, MESH: Occupational Exposure, 0302 clinical medicine, Epidemiology, MESH : Personnel, Hospital, Medicine, 030212 general & internal medicine, MESH : Environmental Monitoring, MESH: Aged, MESH: Middle Aged, Age Factors, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH : Occupational Diseases, Middle Aged, MESH : Adult, 030210 environmental & occupational health, MESH: Case-Control Studies, 3. Good health, Occupational Diseases, MESH : Occupational Exposure, MESH: Young Adult, Health education, epidemiology, MESH : Self Disclosure, MESH: Environmental Monitoring, Environmental Monitoring, Adult, MESH: Occupational Diseases, medicine.medical_specialty, MESH : Case-Control Studies, Self Disclosure, Detergents, MESH : Young Adult, MESH : Asthma, MESH: Personnel, Hospital, Occupational medicine, 03 medical and health sciences, Young Adult, McNemar's test, Environmental health, Occupational Exposure, Humans, MESH : Middle Aged, Asthma, Exposure assessment, Aged, Estimation, MESH: Age Factors, MESH: Humans, business.industry, Gold standard, MESH : Humans, MESH: Disinfectants, Public Health, Environmental and Occupational Health, MESH: Adult, MESH : Detergents, medicine.disease, Personnel, Hospital, MESH : Disinfectants, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Case-Control Studies, Healthcare worker, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH : Age Factors, business, disinfectant, Disinfectants, MESH: Detergents
Abstract: International audience; OBJECTIVES: The aim of the study was to determine whether self-reported occupational exposure to cleaning/disinfecting agents in hospital workers is accurate, in comparison to expert assessment, taken to be the gold standard. METHODS: In the Epidemiological Study of the Genetics and Environment of Asthma (EGEA), participants were interviewed on occupation with a specific questionnaire for hospital workers regarding tasks and cleaning/disinfecting agents. Two estimates of exposure were available: self-report and expert assessment. The expert assessment involved a standardised procedure to estimate intensity, frequency and probability of exposure for each job. The present analysis focused on eight exposures: formaldehyde, glutaraldehyde, bleach/chlorine, alcohol, quaternary ammonium components, ammonia, sprays and latex gloves. Agreement and differences between self-reported and expert estimates were studied by kappa and phi coefficients and McNemar tests, respectively. RESULTS: In the survey of 1571 adults, 176 ever hospital workers (327 occupations) with both self-reported and expert exposure assessments were studied. An underestimation of self-reported exposure was observed especially for formaldehyde (26.5% vs 32.7%, p=0.01), ammonia (7.4% vs 18.8%, p
Published: 2011

17. Factors associated with chronic hepatitis in patients with hepatitis E virus infection who have received solid organ transplants

Author: Jacques Izopet, Pascal Lebray, Marie Essig, Robert N. Santella, Anne Marie Roque-Afonso, Valérie Garrigue, Nada Kanaan, Amelie Cannesson, Nassim Kamar, Elisabeth Cassuto-Viguier, Lionel Rostaing, Elizabeth B. Haagsma, Filomena Conti, Cyril Garrouste, Sven Pischke, Christiane Mousson, Sylvie Radenne, Harry R. Dalton, Jérôme Dumortier, Cecile Chauvet, Eric Thervet, Service de Néphrologie - Hypertension Artérielle Dialyse - Transplantation, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées, Service de virologie, CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Department of Gastroenterology and Hepatology, University Medical Center Groningen [Groningen] (UMCG), Service de Pédiatrie spécialisée, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School [Hannover] (MHH), Département de néphrologie et transplantation, Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), service d'Hépato-gastro-entérologie, Hospices Civiles de Lyon-Hôpital Edouard Heriault, service de néphrologie et transplantation, Centre Hospitalier Universitaire de Nice (CHU Nice), Service de néphrologie adultes [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hépatologie [Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), European Centre for Environment and Human Health, Royal Cornwall Hospital-Universities of Exeter and Plymouth, North Central Kidney Institute, Avera Mckennan Hospital-University Health Center, Service de néphrologie, Saint-Luc Hospital, Service de Néphrologie, Dialyse, Transplantations [CHU Limoges], CHU Limoges, Service de néphrologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service d'hépatologie, Hospices Civils de Lyon (HCL)-Hôpital de la Croix-Rousse [CHU - HCL], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, Laboratoire de Virologie [Purpan], CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Centre de Physiopathologie Toulouse Purpan (ex IFR 30 et IFR 150), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR30-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ), University Medical Center Groningen, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Lapeyronie, Hannover Medical School [Hannover] ( MHH ), Hospices Civils de Lyon ( HCL ) -Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ), CHU Nice, CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Service d'Hépato-Gastroentérologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Hospices Civils de Lyon ( HCL ) -Hôpital de la Croix-Rousse [CHU - HCL], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse, Marquet, Pierre, Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service d'hépatologie [CHU Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Royal Cornwall Hospital-Plymouth University
Subjects: Male, MESH : Retrospective Studies, CYCLOSPORINE-A, medicine.medical_treatment, MESH : Aged, Liver transplantation, medicine.disease_cause, Polymerase Chain Reaction, MESH : Hepatitis E virus, THERAPY, Organ transplantation, MESH : Organ Transplantation, Liver disease, 0302 clinical medicine, Hepatitis E virus, Cyclosporin a, MESH : Female, MESH: Incidence, MESH : Polymerase Chain Reaction, Hepatitis, Chronic, MESH: Aged, 0303 health sciences, MESH: Middle Aged, Incidence, Liver Disease, Gastroenterology, MESH: Follow-Up Studies, Middle Aged, MESH : Adult, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, LIVER-TRANSPLANTATION, MESH : Incidence, 3. Good health, Hepatitis E, Virus, PREVALENCE, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Europe, MESH: Young Adult, BLOOD-DONORS, MESH: RNA, Viral, RNA, Viral, 030211 gastroenterology & hepatology, Female, Adult, MESH: Hepatitis E virus, medicine.medical_specialty, MESH : United States, MESH : Male, MESH: Hepatitis, Chronic, MESH : Europe, MESH : Young Adult, FRANCE, MESH: Organ Transplantation, 03 medical and health sciences, Young Adult, medicine, MESH: United States, Humans, MESH : RNA, Viral, MESH : Hepatitis, Chronic, MESH : Middle Aged, KIDNEY-TRANSPLANT, 030304 developmental biology, Aged, Retrospective Studies, Hepatitis, Transplantation, MESH: Humans, Hepatology, business.industry, MESH : Humans, MESH: Hepatitis E, MESH : Follow-Up Studies, MESH: Adult, MESH: Polymerase Chain Reaction, MESH: Retrospective Studies, Organ Transplantation, medicine.disease, Fibrosis, Tacrolimus, United States, MESH: Male, Chronic infection, RECIPIENTS, [ SDV.SP ] Life Sciences [q-bio]/Pharmaceutical sciences, MESH : Hepatitis E, Immunology, REPLICATION, PEGYLATED INTERFERON-ALPHA, MESH: Europe, business, MESH: Female, Follow-Up Studies
Abstract: International audience; BACKGROUND & AIMS: Hepatitis E virus (HEV) infection can cause chronic hepatitis in recipients of solid organ transplants. However, the factors that contribute to chronic infection and the outcomes of these patients are incompletely understood. We performed a retrospective analysis of data from 17 centers from Europe and the United States that described the progression, outcomes, and factors associated with development of chronic HEV infection in recipients of transplanted solid organs. METHODS: We studied data from 85 recipients of solid organ transplants who were infected with HEV. Chronic HEV infection was defined by the persistent increases in levels of liver enzymes and polymerase chain reaction evidence of HEV in the serum and/or stool for at least 6 months. RESULTS: Fifty-six patients (65.9%) developed chronic hepatitis. Univariate analysis associated liver transplant, shorter times since transplant, lower levels of liver enzymes and serum creatinine, lower platelet counts, and tacrolimus-based immunosuppressive therapy (rather than cyclosporin A) with chronic hepatitis. On multivariate analysis, the independent predictive factors associated with chronic HEV infection were the use of tacrolimus rather than cyclosporin A (odds ratio [OR], 1.87; 95% confidence interval [CI], 1.49-1.97; P = .004) and a low platelet count at the time of diagnosis with HEV infection (OR, 1.02; 95% CI, 1.001-1.1; P = .04). Of patients with chronic hepatitis, 18 (32.1%) achieved viral clearance after the dose of immunosuppressive therapy was reduced. No HEV reactivation was observed after HEV clearance. CONCLUSIONS: HEV infection causes chronic hepatitis in more than 60% of recipients of solid organ transplants. Tacrolimus therapy is the main predictive factor for chronic hepatitis. Dose reductions of immunosuppressive therapy resulted in viral clearance in more than 30% of patients.
Published: 2011

18. Incidence of sarcoma histotypes and molecular subtypes in a prospective epidemiological study with central pathology review and molecular testing

Author: Pierre-Paul Bringuier, Christophe Bergeron, Luc Istier, Laurent Alberti, Philippe Chalabreysse, A. Lurkin, Dominic Cellier, Michel Peoc'h, Françoise Ducimetière, Jean-Yves Blay, Isabelle Ray-Coquard, Anne-Valérie Decouvelaere, Anne-Marie Schott, Dominique Ranchère-Vince, Christine B. Müller, Jean-Yves Scoazec, Département d'Oncologie Médicale, Centre Léon Bérard [Lyon]-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Santé-Individu-Société 'SIS', Centre Léon Bérard [Lyon], Département d'anatomopathologie, biopathologie, Biologie, Ingénierie et Imagerie de la Greffe de Cornée ( EA 2521, JE2521, IFR143 ), Université Jean Monnet [Saint-Étienne] ( UJM ), Institute of Functional Interfaces, Karlsruhe Institute of Technology ( KIT ), Equipe 11, Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Equipe 4, equipe 4, Laboratoire Central d'Anatomie et de Cytologie Pathologiques [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ) -Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ) -Centre de Recherche en Cancérologie de Lyon ( CRCL ), Département d'information médicale, Hospices Civils de Lyon ( HCL ) -Université de Lyon, Service d'Oncologie, Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] ( IHOPe ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Merck Serono, Parcours santé systémique (P2S), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Biologie, Ingénierie et Imagerie pour l'Ophtalmologie (BIIO), Université Jean Monnet - Saint-Étienne (UJM), Karlsruhe Institute of Technology (KIT), Oncogénèse et progression tumorale, Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL)-Université de Lyon, Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] (IHOPe), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Merck & Co. Inc, Santé Individu Société (SIS), Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie, Ingénierie et Imagerie de la Greffe de Cornée (EA 2521, JE2521, IFR143), Université Jean Monnet [Saint-Étienne] (UJM), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Santé Individu Société - SIS (SIS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Moulin - Lyon 3 (UJML), and Université de Lyon-Université Lumière - Lyon 2 (UL2)
Subjects: Male, Pathology, Epidemiology, MESH : Prospective Studies, MESH : Aged, Soft Tissue Neoplasms, MESH : Sarcoma, Kaposi, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, MESH : Female, Prospective Studies, MESH: Incidence, Prospective cohort study, MESH: Aged, 0303 health sciences, education.field_of_study, MESH: Middle Aged, MESH: Epidemiologic Studies, Multidisciplinary, Incidence, Incidence (epidemiology), Sarcoma, Middle Aged, MESH : Adult, MESH: Bone Neoplasms, MESH : Incidence, 3. Good health, Oncology, MESH: Young Adult, 030220 oncology & carcinogenesis, Medicine, Female, Cancer Epidemiology, Research Article, MESH: Soft Tissue Neoplasms, Adult, Leiomyosarcoma, medicine.medical_specialty, Adolescent, MESH : Male, Science, Population, MESH : Young Adult, Bone Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Liposarcoma, Bone Sarcoma, MESH : Sarcoma, MESH : Epidemiologic Studies, Young Adult, 03 medical and health sciences, Internal medicine, MESH : Adolescent, medicine, Humans, MESH : Middle Aged, education, Sarcoma, Kaposi, Aged, 030304 developmental biology, MESH : Bone Neoplasms, MESH: Adolescent, MESH: Humans, business.industry, MESH : Humans, MESH: Adult, medicine.disease, MESH: Male, MESH: Prospective Studies, Epidemiologic Studies, MESH: Sarcoma, MESH: Sarcoma, Kaposi, business, MESH: Female, MESH : Soft Tissue Neoplasms
Abstract: International audience; BACKGROUND: The exact overall incidence of sarcoma and sarcoma subtypes is not known. The objective of the present population-based study was to determine this incidence in a European region (Rhone-Alpes) of six million inhabitants, based on a central pathological review of the cases. METHODOLOGY/PRINCIPAL FINDINGS: From March 2005 to February 2007, pathology reports and tumor blocks were prospectively collected from the 158 pathologists of the Rhone-Alpes region. All diagnosed or suspected cases of sarcoma were collected, reviewed centrally, examined for molecular alterations and classified according to the 2002 World Health Organization classification. Of the 1287 patients screened during the study period, 748 met the criteria for inclusion in the study. The overall crude and world age-standardized incidence rates were respectively 6.2 and 4.8 per 100,000/year. Incidence rates for soft tissue, visceral and bone sarcomas were respectively 3.6, 2.0 and 0.6 per 100,000. The most frequent histological subtypes were gastrointestinal stromal tumor (18%; 1.1/100,000), unclassified sarcoma (16%; 1/100,000), liposarcoma (15%; 0.9/100,000) and leiomyosarcoma (11%; 0.7/100,000). CONCLUSIONS/SIGNIFICANCE: The observed incidence of sarcomas was higher than expected. This study is the first detailed investigation of the crude incidence of histological and molecular subtypes of sarcomas.
Published: 2011

19. Squamous cell carcinomas are associated with verrucokeratotic cutaneous lesions but not with common warts in organ-transplant patients. A case-control study

Author: Michel D'Incan, Marie-Françoise Avril, Sylvie Euvrard, Céleste Lebbé, Stéphane Barete, Sylvie Bastuji-Garin, Camille Francès, François Aubin, Pascal Joly, Guillaume Lair, D. Penso-Assathiany, Service de santé publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Department of Dermatology, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Département de dermatologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de Dermatologie, Hôtel-Dieu, Service de dermatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), CHU Tenon [AP-HP], Clinique Dermatologique, Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques-Université de Franche-Comté ( UFC ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 ( UPD5 ), CHU Tenon [APHP], Hospices Civils de Lyon ( HCL ) -Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté [COMUE] ( UBFC ) -Université de Franche-Comté ( UFC ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Saint-Jacques-Université de Franche-Comté (UFC), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 (UPD5)
Subjects: Graft Rejection, Male, Skin Neoplasms, Time Factors, MESH : Heart Transplantation, MESH : Aged, MESH : Prospective Studies, Azathioprine, Organ transplantation, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Kidney Transplantation, 030207 dermatology & venereal diseases, 0302 clinical medicine, Risk Factors, MESH: Risk Factors, MESH : Female, Prospective Studies, MESH : Carcinoma, Squamous Cell, Skin, MESH: Aged, MESH: Middle Aged, virus diseases, MESH: Heart Transplantation, MESH: Carcinoma, Squamous Cell, MESH: Follow-Up Studies, Middle Aged, MESH : Risk Factors, MESH: Case-Control Studies, 3. Good health, 030220 oncology & carcinogenesis, Carcinoma, Squamous Cell, Prednisolone, Female, France, Warts, MESH : Skin Diseases, medicine.drug, MESH : Time Factors, medicine.medical_specialty, MESH : Case-Control Studies, MESH : Male, MESH: Skin Diseases, MESH: Graft Rejection, [SDV.CAN]Life Sciences [q-bio]/Cancer, Skin Diseases, 03 medical and health sciences, MESH: Skin, medicine, Carcinoma, MESH : Skin, Humans, MESH : Middle Aged, MESH : France, neoplasms, Common warts, Aged, Transplantation, MESH : Warts, MESH: Humans, business.industry, MESH: Skin Neoplasms, Actinic keratosis, MESH : Skin Neoplasms, MESH : Humans, MESH: Time Factors, MESH: Warts, MESH : Graft Rejection, MESH : Follow-Up Studies, Odds ratio, medicine.disease, Kidney Transplantation, Dermatology, MESH: Male, MESH: Prospective Studies, MESH: France, Case-Control Studies, Heart Transplantation, MESH : Kidney Transplantation, business, MESH: Female, Follow-Up Studies
Abstract: Background Warts are thought to be associated with the development of squamous cell carcinoma (SCC) in organ transplant patients. We investigated the association between the different types of warts and SCC in organ transplant patients. Methods A prospective multicenter case-control study was conducted. Cases were patients with a kidney or heart transplant who were referred for a SCC. Controls were organ transplant patients without SCC, individually matched for age, gender, type of organ transplant (heart or kidney), skin phototype, time from transplantation, and center. Four types of warts: flat warts, verrucae vulgares (including palmo-plantar warts and common warts), verrucous papilloma, and verrucokeratotic lesions were compared between cases and controls using conditional logistic regression. Results Ninety-nine cases and 169 controls were included. In multivariate analysis, number of rejections, azathioprine, prednisolone and anti-lymphocyte anti-serum or anti-CD3 monoclonal antibodies use, cumulative sun exposure, actinic keratosis, and verrucokeratic lesions (odds ratio [OR] 16.50; 95% confidence interval [CI] 2.82-96.80) were independently associated with SCC, whereas the association with verrucous papilloma was borderline significant (OR 2.21; 95% CI 0.97-8.15). The association between the presence of at least one of these two types of warts (verruco-keratotic lesions and verrucous papilloma) and the occurrence of SCC was highly significant (OR 18.36; 95% CI 3.03-111) when these warts were located in the same area than SCC, whereas no significant association was evidenced when these warts were located in another area (OR 1.02; 95% CI 0.13-5.79). Conclusion Verrucous papilloma and mainly verrucokeratotic lesions are strongly associated with the risk of SCC in organ transplant patients, whereas the most typical types of warts: verrucae vulgares and flat warts, are not.
Published: 2010

20. Birt-Hogg-Dubé renal tumors are genetically distinct from other renal neoplasias and are associated with up-regulation of mitochondrial gene expression

Author: Markus Aly, Stéphane Richard, Jeffrey P. MacKeigan, Viorel Vasiliu, Arnaud Mejean, Jeff Klomp, Magnus Nordenskjöld, Natalie M. Niemi, Yves Denoux, Peter Zickert, Sophie Giraud, Bin Tean Teh, Kyle A. Furge, Karl Dykema, David Petillo, Ximing J. Yang, Jindong Chen, Annika Sääf, Sophie Gad, L. Yonneau, Ulf S.R. Bergerheim, BMC, Ed., Laboratory of Computational Biology, Van Andel Institute [Grand Rapids], Laboratory of Cancer Genetics, Laboratory of Systems Biology, Division of Surgical Pathology, Northwestern University Feinberg School of Medicine, Department of Molecular Medicine and Surgery and Center for Molecular Medicine, Karolinska Institutet [Stockholm], Department of Pathology, Karolinska University Hospital [Stockholm], Danderyds sjukhus = Danderyd University Hospital, Cytokines et Immunologie des Tumeurs Humaines (U753), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Génétique, Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre de Références Cancers Rares (PREDIR), INCA, Service d'urologie, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service d'anatomie pathologique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Urologie, Hôpital Foch [Suresnes], NCCS-VARI Translational Research Laboratory, National Cancer Centre of Singapore, This work was supported by the French NCI (Institut National du Cancer, PNES rein) and the Ligue Nationale contre le Cancer (Comités du Cher et de l'Indre)., Division of Urology, Department of Surgery, Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Université Paris-Sud - Paris 11 (UP11) - Institut Gustave Roussy (IGR) - Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL) - Hôpital Edouard Herriot [CHU - HCL], Université Paris-Sud - Paris 11 (UP11) - Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Bicêtre, CHU Necker - Enfants Malades [AP-HP] - Assistance publique - Hôpitaux de Paris (AP-HP), CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: MESH: Signal Transduction, MESH : Transcription Factors, Chromophobe Renal Cell Carcinoma, MESH: Heat-Shock Proteins, urologic and male genital diseases, Oxidative Phosphorylation, Birt-Hogg-Dube Syndrome, MESH : Carcinoma, Renal Cell, 0302 clinical medicine, Renal cell carcinoma, MESH: Up-Regulation, Adenoma, Oxyphilic, Genetics(clinical), Renal oncocytoma, MESH : Up-Regulation, Genetics (clinical), Heat-Shock Proteins, MESH: Estrone, 0303 health sciences, MESH : Genes, Mitochondrial, MESH: Mitochondrial Proteins, MESH: Transcription Factors, MESH: Carcinoma, Renal Cell, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Kidney Neoplasms, 3. Good health, Up-Regulation, DNA-Binding Proteins, Genes, Mitochondrial, MESH: Birt-Hogg-Dube Syndrome, 030220 oncology & carcinogenesis, MESH : Oxidative Phosphorylation, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH : DNA-Binding Proteins, Research Article, Signal Transduction, lcsh:Internal medicine, lcsh:QH426-470, Adenoma, MESH: Adenoma, Oxyphilic, Biology, MESH: Genes, Mitochondrial, Mitochondrial Proteins, 03 medical and health sciences, Germline mutation, MESH: Oxidative Phosphorylation, Proto-Oncogene Proteins, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH : Adenoma, Oxyphilic, Carcinoma, medicine, Genetics, Humans, Folliculin, lcsh:RC31-1245, Carcinoma, Renal Cell, MESH : Mitochondrial Proteins, 030304 developmental biology, MESH : Signal Transduction, MESH: Humans, Tumor Suppressor Proteins, MESH : Humans, MESH : Heat-Shock Proteins, medicine.disease, Human genetics, MESH : Kidney Neoplasms, lcsh:Genetics, MESH : Estrone, MESH : Birt-Hogg-Dube Syndrome, Cancer research, MESH: Kidney Neoplasms, MESH: DNA-Binding Proteins, Transcription Factors
Abstract: Background Germline mutations in the folliculin (FLCN) gene are associated with the development of Birt-Hogg-Dubé syndrome (BHDS), a disease characterized by papular skin lesions, a high occurrence of spontaneous pneumothorax, and the development of renal neoplasias. The majority of renal tumors that arise in BHDS-affected individuals are histologically similar to sporadic chromophobe renal cell carcinoma (RCC) and sporadic renal oncocytoma. However, most sporadic tumors lack FLCN mutations and the extent to which the BHDS-derived renal tumors share genetic defects associated with the sporadic tumors has not been well studied. Methods BHDS individuals were identified symptomatically and FLCN mutations were confirmed by DNA sequencing. Comparative gene expression profiling analyses were carried out on renal tumors isolated from individuals afflicted with BHDS and a panel of sporadic renal tumors of different subtypes using discriminate and clustering approaches. qRT-PCR was used to confirm selected results of the gene expression analyses. We further analyzed differentially expressed genes using gene set enrichment analysis and pathway analysis approaches. Pathway analysis results were confirmed by generation of independent pathway signatures and application to additional datasets. Results Renal tumors isolated from individuals with BHDS showed distinct gene expression and cytogenetic characteristics from sporadic renal oncocytoma and chromophobe RCC. The most prominent molecular feature of BHDS-derived kidney tumors was high expression of mitochondria-and oxidative phosphorylation (OXPHOS)-associated genes. This mitochondria expression phenotype was associated with deregulation of the PGC-1α-TFAM signaling axis. Loss of FLCN expression across various tumor types is also associated with increased nuclear mitochondrial gene expression. Conclusions Our results support a genetic distinction between BHDS-associated tumors and other renal neoplasias. In addition, deregulation of the PGC-1α-TFAM signaling axis is most pronounced in renal tumors that harbor FLCN mutations and in tumors from other organs that have relatively low expression of FLCN. These results are consistent with the recently discovered interaction between FLCN and AMPK and support a model in which FLCN is a regulator of mitochondrial function.
Published: 2010

21. Evidence that graft-site candidiasis after kidney transplantation is acquired during organ recovery: a multicenter study in France

Author: Albano , Laetitia, Bretagne , Stéphane, Mamzer-Bruneel , Marie-France, Kacso , Irina, Desnos-Ollivier , Marie, Guerrini , Patrice, Le Luong , Thanh, Cassuto , Elisabeth, Dromer , Françoise, Lortholary , Olivier, Gangneux , Jean-Pierre, Service de néphrologie, Hôpital Pasteur [Nice] ( CHU ), Service de parasitologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Mycologie moléculaire, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Service de néphrologie adultes [CHU Necker], CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Agence de la biomédecine [Saint-Denis la Plaine], Service de transplantation, Hospices Civils de Lyon ( HCL ) -Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ), Centre d'infectiologie Necker-Pasteur [CHU Necker], Signalisation et Réponses aux Agents Infectieux et Chimiques ( SeRAIC ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR140, Service de Parasitologie-Mycologie [Rennes], Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Hôpital Pasteur [Nice] (CHU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Université de Rennes (UR), and Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes]
Subjects: Male, MESH : Retrospective Studies, medicine.medical_treatment, MESH : Aged, MESH : Genotype, 030230 surgery, MESH: Kidney Transplantation, MESH: Genotype, MESH : Candidiasis, 0302 clinical medicine, MESH: Risk Factors, Risk Factors, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, MESH : Female, MESH: Incidence, Abscess, Candida albicans, Kidney transplantation, MESH: Treatment Outcome, Candida, MESH: Aged, 0303 health sciences, Kidney, MESH: Middle Aged, biology, Incidence, Candidiasis, Middle Aged, MESH : Adult, MESH : Risk Factors, MESH: Candidiasis, Urinoma, Nephrectomy, MESH : Incidence, 3. Good health, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Treatment Outcome, Infectious Diseases, medicine.anatomical_structure, surgical procedures, operative, Female, France, Adult, Microbiology (medical), medicine.medical_specialty, Genotype, MESH : Male, MESH : Treatment Outcome, 03 medical and health sciences, MESH: Candida, medicine, Humans, MESH : Middle Aged, Arteritis, MESH : France, Aged, Retrospective Studies, MESH: Humans, 030306 microbiology, business.industry, MESH : Humans, MESH: Adult, MESH: Retrospective Studies, medicine.disease, biology.organism_classification, Kidney Transplantation, MESH: Male, Surgery, MESH: France, Transplantation, MESH : Kidney Transplantation, business, MESH: Female, MESH : Candida
Abstract: International audience; BACKGROUND: Infections of renal grafts with Candida species can induce life-threatening complications in the recipient. METHODS: A 9-year retrospective study involving all of the transplant centers in France was designed to determine the incidence, origin, characteristics, and outcome of graft-site candidiasis that occurred after kidney transplantation. Yeasts cultured from preservation or drainage solutions and graft specimens were recorded. RESULTS: Among 18,617 kidney grafts, 18 recipients corresponding to 12 donors developed culture-confirmed graft-site candidiasis (incidence, 1 case per 1000 grafts) a median of 25 days after the graft procedure. Clinical presentations included 14 cases of renal arteritis (13 were complicated by aneurysm), 1 urinoma, 2 graft site abscesses, and 1 surgical site infection. Candida albicans was involved in 13 cases. A unique C. albicans genotype or a single rare Candida species was involved in each episode. Together with the clinical history, these findings demonstrate that organ contamination followed by transmission to the recipient occurred during recovery. Therapeutic management varied from simple monitoring in 1 case to a combination of surgery (nephrectomy in 9 cases and arterial bypass in 9 cases) and antifungal therapy (14 cases). Overall, 3 of 18 kidney transplant recipients died, and 9 had their graft surgically removed. CONCLUSION: Graft-transmitted candidiasis that ends most often in fungal arteritis is associated with high morbidity and mortality after kidney transplantation and is related to organ contamination during recovery in the donor.
Published: 2009

22. DHA supplementation and immune function

Author: Mebarek, Saïda, Ermak, Natalia, Benzaria, Amal, Vicca, Stéphanie, Dubois, Madeleine, Némoz, Georges, Laville, Martine, Lacour, Bernard, Véricel, Evelyne, Lagarde, Michel, Prigent, Annie-France, Service de Diabétologie et Nutrition, Hospices Civils de Lyon ( HCL ) -Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ), Régulations métaboliques, nutrition et diabètes - UM55 ( RMND UM55 ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA ), Nutrition Lipidique et Régulation Fonctionnelle du Coeur et des Vaisseaux ( NLRFC ), Institut National de la Recherche Agronomique ( INRA ) -Université Paris-Sud - Paris 11 ( UP11 ), Service de Biochimie A [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre de recherche Croissance et signalisation ( UMR_S 845 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), This work was funded by Inserm and a grant from the Groupe Lipides Nutrition (GLN) (2005)., Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Nutrition Lipidique et Régulation Fonctionnelle du Coeur et des Vaisseaux (NLRFC), Institut National de la Recherche Agronomique (INRA)-Université Paris-Sud - Paris 11 (UP11), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche Croissance et signalisation (UMR_S 845), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Université Paris-Sud - Paris 11 (UP11)-Institut National de la Recherche Agronomique (INRA), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: mitochondrial membrane potential, oxidized LDL, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, DHA enrichment, food and beverages, lipids (amino acids, peptides, and proteins), interleukin-2, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: International audience; Dietary intake of long-chain n-3 PUFA has been reported to decrease several markers of lymphocyte activation and modulate monocyte susceptibility to apoptosis. However, most human studies examined the combined effect of DHA and EPA using relatively high daily amounts of n-3 PUFA. The present study investigated the effects of increasing doses of DHA added to the regular diet of human healthy volunteers on lymphocyte response to tetradecanoylphorbol acetate plus ionomycin activation, and on monocyte apoptosis induced by oxidized LDL. Eight subjects were supplemented with increasing daily doses of DHA (200, 400, 800, 1600 mg) in a TAG form containing DHA as the only PUFA, for 2 weeks each dose. DHA intake dose-dependently increased the proportion of DHA in mononuclear cell phospholipids, the augmentation being significant after 400 mg DHA/d. The tetradecanoylphorbol acetate plus ionomycin-stimulated IL-2 mRNA level started to increase after ingestion of 400 mg DHA/d, with a maximum after 800 mg intake, and was positively correlated (P < 0.003) with DHA enrichment in cell phospholipids. The treatment of monocytes by oxidized LDL before DHA supplementation drastically reduced mitochondrial membrane potential as compared with native LDL treatment. Oxidized LDL apoptotic effect was significantly attenuated after 400 mg DHA/d and the protective effect was maintained throughout the experiment, although to a lesser extent at higher doses. The present results show that supplementation of the human diet with low DHA dosages improves lymphocyte activability. It also increases monocyte resistance to oxidized LDL-induced apoptosis, which may be beneficial in the prevention of atherosclerosis.
Published: 2008

23. Renal function with delayed or immediate cyclosporine microemulsion in combination with enteric-coated mycophenolate sodium and steroids: results of follow up to 30 months post-transplant

Author: Mourad , Georges, Karras , Alexandre, Kamar , Nassim, Garrigue , Valérie, Legendre , Christophe, Lefrançois , Nicole, Charpentier , Bernard, Bourbigot , Bernard, Pouteil-Noble , Claire, Bayle , François, Lebranchu , Yvon, Mariat , Christophe, Le Meur , Yann, Kessler , Michèle, Moulin , Bruno, Ducloux , Didier, Delahousse , Michel, Lang , Philippe, Merville , Pierre, Chaouche-Teyara , Kamel, Rostaing , Lionel, Service de Pédiatrie spécialisée, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Service de néphrologie adultes [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Néphrologie - Hypertension Artérielle Dialyse - Transplantation, Service de transplantation, Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Service de néphrologie, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Greffes d'Epitheliums et Regulation de l'Activation Lymphocytaire, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Service de néphrologie et transplantation, Hospices Civils de Lyon (HCL)-Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Service de néphrologie, dialyse, aphérèses et transplantation, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), Service de néphrologie et tranplantation, CHU Saint-Etienne-Hôpital nord, Service de Néphrologie, Dialyse, Transplantations [CHU Limoges], CHU Limoges, Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Néphrologie et Transplantation, CHU Strasbourg, Service d'urologie, andrologie et transplantation rénale, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de transplantation rénale, Hôpital Foch [Suresnes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Novartis France SAS, Novartis Pharma S.A.S., The French Myriade FR01 Study Group, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de néphrologie et immunologie clinique, Hôpital Bretonneau-Université de Tours-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Saas, Philippe, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Lapeyronie, CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Hospices Civils de Lyon ( HCL ) -Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ) -Hôpital de la Cavale Blanche - CHRU Brest ( CHU - BREST ), Hospices Civils de Lyon ( HCL ) -Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble, Hôpital Bretonneau-Université de Tours-CHRU Tours, Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Service de Néphrologie et Urologie, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), and Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 )
Subjects: Male, Time Factors, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH : Male, MESH: Creatinine, MESH: Tablets, Enteric-Coated, Kidney, Kidney Function Tests, MESH: Cyclosporine, MESH: Kidney Transplantation, MESH : Cyclosporine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Humans, MESH : Middle Aged, MESH : Female, MESH : Immunosuppressive Agents, MESH: Middle Aged, MESH: Humans, MESH : Drug Therapy, Combination, MESH : Humans, MESH : Kidney Function Tests, MESH: Time Factors, MESH : Creatinine, MESH : Follow-Up Studies, MESH: Follow-Up Studies, MESH: Kidney, MESH : Tablets, Enteric-Coated, Middle Aged, Kidney Transplantation, MESH : Kidney, MESH: Male, MESH: Drug Therapy, Combination, MESH: Kidney Function Tests, Creatinine, Cyclosporine, MESH : Kidney Transplantation, [SDV.IMM]Life Sciences [q-bio]/Immunology, Drug Therapy, Combination, Female, Tablets, Enteric-Coated, MESH: Immunosuppressive Agents, MESH: Female, Immunosuppressive Agents, MESH : Time Factors, Follow-Up Studies
Abstract: International audience; BACKGROUND: In the multicenter, open-label Myriade study, renal transplant patients were randomized to early cyclosporine microemulsion (CsA-ME, day 0) or delayed CsA-ME (day 6) with enteric-coated mycophenolate sodium (EC-MPS), steroids and interleukin-2 receptor induction. One-yr results have been published previously. We now report the results of an extension study in which patients were followed up for a period of three yr post-transplant. METHODS: All patients completing the one-yr core study on-treatment were eligible to enter the extension study. RESULTS: Of the 203 patients, 153 completed the core trial on-treatment; 144 (94%) entered the extension study with a minimum follow-up of one yr (73 early CsA-ME, 71 delayed CsA-ME). In 75% of patients receiving EC-MPS during the extension, the recommended dose was administered (1440 mg/d). Median creatinine clearance remained constant (57 mL/min) at 12, 24 and 30 months post-transplant and was similar in the early and delayed CsA-ME groups as well as in subpopulations with or without delayed graft function. One patient in the early CsA-ME group died. No grafts were lost. The incidence of BPAR from time of transplant to the end of the extension study was 17% (24/139). Seven patients (5%) discontinued the extension study prematurely because of adverse events. CONCLUSION: These results suggest that a regimen of CsA-ME, EC-MPS and steroids results in excellent survival rates with stable renal function over a mean follow-up of 30 months. Immediate introduction of CsA-ME has no deleterious effect on long-term renal function, even among patients with delayed graft function.
Published: 2007

24. Methotrexate therapy for rheumatoid arthritis: clinical practice guidelines based on published evidence and expert opinion

Author: Thierry Schaeverbeke, Jean Sibilia, Philippe Goupille, Arnaud Constantin, Xavier Mariette, Bernard Combe, Jacques Tebib, Thao Pham, D. Wendling, Xavier Puéchal, René-Marc Flipo, Jean-Francis Maillefert, Stephan Pavy, Maxime Dougados, Laure Gossec, Alain Cantagrel, Xavier Le Loët, Service de Rhumatologie [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille ( APHM ) -Hôpital de la Conception [CHU - APHM] ( LA CONCEPTION ), Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques, Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Lapeyronie, Service de Rhumatologie, Hôpital Claude Huriez-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Service de rhumatologie, CHRU Tours, Service de rhumatologie [Rouen], CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Service de médecine interne et centre de référence des maladies rares [CHU Cochin], CHU Bordeaux [Bordeaux], Service de rhumatologie [Strasbourg], CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Service d'immunologie et rhumatologie, Hospices Civils de Lyon ( HCL ) -Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ), Agents pathogènes et inflammation - UFC (EA 4266) ( API ), Université de Franche-Comté ( UFC ), Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques (U738 / UMR_S738), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de rhumatologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Agents pathogènes et inflammation - UFC (EA 4266) (API), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Hôpital Cochin [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: MESH : Retrospective Studies, Arthritis, Pulmonary function testing, Arthritis, Rheumatoid, 0302 clinical medicine, MESH: Practice Guidelines as Topic, 030212 general & internal medicine, MESH : Immunosuppressive Agents, MESH: Treatment Outcome, MESH: Arthritis, Rheumatoid, MESH : Evidence-Based Medicine, Evidence-Based Medicine, MESH: Follow-Up Studies, 3. Good health, MESH : Practice Guidelines as Topic, MESH: Methotrexate, Treatment Outcome, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Rheumatoid arthritis, Practice Guidelines as Topic, MESH: Immunosuppressive Agents, Immunosuppressive Agents, medicine.drug, medicine.medical_specialty, Renal function, MESH : Treatment Outcome, [ SDV.MHEP.RSOA ] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, 03 medical and health sciences, Rheumatology, Internal medicine, medicine, Humans, Retrospective Studies, 030203 arthritis & rheumatology, MESH: Humans, business.industry, MESH : Humans, MESH: Retrospective Studies, MESH : Follow-Up Studies, Evidence-based medicine, medicine.disease, Methotrexate, MESH : Methotrexate, MESH : Arthritis, Rheumatoid, Physical therapy, business, Rheumatism, MESH: Evidence-Based Medicine, Follow-Up Studies
Abstract: International audience; OBJECTIVES: To develop clinical practice guidelines for the use of methotrexate in rheumatoid arthritis (RA), using the evidence-based approach and expert opinion. METHODS: A scientific committee used a Delphi procedure to select five questions, which formed the basis for developing recommendations. Evidence providing answers to the five questions was sought in the Cochrane databases, PubMed, and proceedings of meetings of the French Society for Rheumatology, European League Against Rheumatism, and American College of Rheumatology. Using this evidence, a group of rheumatologists developed and validated the recommendations. For each recommendation, the level of evidence and the extent of agreement among experts were specified. RESULTS: The recommendations were as follows: 1: The starting dosage for methotrexate in patients with RA should not be less than 10 mg/week and should be determined based on disease severity and patient-related factors; 2: When a patient with RA shows an inadequate response to methotrexate, the dosage should be increased at intervals of 6 weeks, up to 20 mg/week, according to tolerance and patient-related factors; 3: When starting methotrexate treatment in a patient with RA, preference should be given to the oral route. A switch to the intramuscular or subcutaneous route should be considered in patients with poor compliance, inadequate effectiveness, or gastrointestinal side effects; 4: At present, there is no evidence indicating that a change in methotrexate dosage is in order when a TNF antagonist is given concomitantly; 5: The investigations that are mandatory before starting methotrexate therapy in a patient with RA consist of a full blood cell count, serum transaminase levels, serum creatinine with computation of creatinine clearance, and a chest radiograph. In addition, serological tests for the hepatitis viruses B and C and a serum albumin assay are recommended. In patients with a history of respiratory disease or current respiratory symptoms, lung function tests with determination of the diffusing capacity for carbon monoxide are recommended; 6: Investigations that are mandatory for monitoring methotrexate therapy in patients with RA consist of full blood cell counts and serum transaminase and creatinine assays. These tests should be obtained at least once a month for the first 3 months then every 4-12 weeks; 7: Folate supplementation can be given routinely to patients treated with methotrexate for RA. In practice, a minimal dosage of 5 mg of folic acid once a week, at a distance from the methotrexate dose, is appropriate; 8: In the event of respiratory symptoms possibly related to methotrexate toxicity, the drug must be stopped and symptom severity evaluated. Should evidence of serious disease be found, the patient should be admitted immediately or advice from a pulmonologist should be obtained immediately. CONCLUSION: Recommendations about methotrexate therapy for RA were developed. These recommendations should help to improve practice uniformity and, ultimately, to improve the management of RA.
Published: 2006

25. First-in-human use of a marine oxygen carrier (M101) for organ preservation: A safety and proof-of-principle study

Author: Le Meur, Yannick, Badet, Lionel, Essig, Marie, Thierry, Antoine, Büchler, Matthias, Drouin, Sarah, Deruelle, Charles, Morelon, Emmanuel, Pesteil, Francis, Delpech, Pierre-Olivier, Boutin, Jean-Michel, Renard, Felix, Barrou, Benoit, Delpech, Pierre‐Olivier, Boutin, Jean‐Michel, Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHRU Brest - Service de Nephrologie (CHU - BREST - Nephrologie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service d'urologie [Hôpital Edouard-Herriot, CHU-HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de Néphrologie, Dialyse, Transplantations [CHU Limoges], CHU Limoges, Service de Néphrologie-Hémodialyse-Transplantation rénale [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), Service d'Urologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHRU de Brest, service de chirurgie urologique et de la transplantation reinale (CHU - BREST - Urologie), Service de Transplantation, Néphrologie et Immunologie Clinique [Hôpital Edouard Herriot, HCL], Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Service de Chirurgie Thoracique et Vasculaire - Médecine vasculaire [CHU Limoges], Service d'urologie [CHU de Poitiers], Service d'urologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Service d'Urologie [Poitiers], Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Service de néphrologie et immunologie clinique [CHRU Tours] (EA4245 UT), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours-Hôpital Bretonneau
Subjects: medicine.medical_specialty, delayed graft function (DGF), Organ Preservation Solutions, 030232 urology & nephrology, Ischemia, Urology, Cold storage, Renal function, kidney transplantation/nephrology, 030230 surgery, Kidney, clinical research/practice, Cold Ischemia Time, Microcirculation, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Immunology and Allergy, organ transplantation in general, Pharmacology (medical), Adverse effect, Transplantation, Machine perfusion, business.industry, Graft Survival, clinical trial, Organ Preservation, medicine.disease, Kidney Transplantation, Thrombosis, Tissue Donors, 3. Good health, Oxygen, Perfusion, ischemia reperfusion injury (IRI), [SDV.IMM]Life Sciences [q-bio]/Immunology, business
Abstract: International audience; The medical device M101 is an extracellular hemoglobin featuring high oxygen-carrying capabilities. Preclinical studies demonstrated its safety as an additive to organ preservation solutions and its beneficial effect on ischemia/reperfusion injuries. OXYgen carrier for Organ Preservation (OXYOP) is a multicenter open-label study evaluating for the first time the safety of M101 added (1 g/L) to the preservation solution of one of two kidneys from the same donor. All adverse events (AEs) were analyzed by an independent data and safety monitoring board. Among the 58 donors, 38% were extended criteria donors. Grafts were preserved in cold storage (64%) or machine perfusion (36%) with a mean cold ischemia time (CIT) of 740 minutes. At 3 months, 490 AEs (41 serious) were reported, including two graft losses and two acute rejections (3.4%). No immunological, allergic, or prothrombotic effects were reported. Preimplantation and 3-month biopsies did not show thrombosis or altered microcirculation. Secondary efficacy end points showed less delayed graft function (DGF) and better renal function in the M101 group than in the contralateral kidneys. In the subgroup of grafts preserved in cold storage, Kaplan-Meier survival and Cox regression analysis showed beneficial effects on DGF independent of CIT (P = .048). This study confirms that M101 is safe and shows promising efficacy data.
Published: 2020

26. Outcomes in antiretroviral-naive HIV-infected patients initiating therapy with TDF/FTC plus either atazanavir/r or another third recommended drug

Author: J.-M. Livrozet, Jade Ghosn, Eric Billaud, Odile Launay, Jean-Luc Meynard, J. Pavie, Jean-Marc Lacombe, Dominique Costagliola, A Abgrall, BMC, Ed., Centre hospitalier universitaire de Nantes (CHU Nantes), Epidémiologie, stratégies thérapeutiques et virologie cliniques dans l'infection à VIH, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine interne et maladies infectieuses, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, CIC Cochin Pasteur (CIC 1417), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Université Paris Descartes - Paris 5 (UPD5)-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Immunologie Clinique, Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de maladies infectieuses et tropicales [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier universitaire de Nantes ( CHU Nantes ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, CIC Cochin Pasteur ( CIC 1417 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP]-Hôtel-Dieu-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Hospices Civils de Lyon ( HCL ) -Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ), Service des maladies infectieuses et tropicales [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Drug, medicine.medical_specialty, media_common.quotation_subject, 030312 virology, 03 medical and health sciences, 0302 clinical medicine, Pharmacotherapy, Acquired immunodeficiency syndrome (AIDS), [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, International congress, medicine, Antiretroviral naive, Hiv infected patients, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, media_common, 0303 health sciences, business.industry, Public Health, Environmental and Occupational Health, medicine.disease, 3. Good health, Discontinuation, Atazanavir, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Infectious Diseases, Poster Presentation, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, ComputingMethodologies_GENERAL, business, medicine.drug
Abstract: Atazanavir/r (ATV/r) is a recommended PI option for treating ART-naive patients in recent guidelines. TDF/FTC is the most commonly used recommended backbone in this setting. Our objectives were to compare times 1) to discontinuation of the third drug, 2) to virologic suppression (VL< 50 copies/ml), with discontinuation of the third drug considered as failure, 3) to an increase of at least 100 CD4 cells/mm 3 , with discontinuation of the third drug considered as failure, 4) to AIDS or death from any cause, with an intention to continue approach 5) to hospitalization, AIDS or death with an intention to continue approach in patients initiating with ATV/r or another recommended third drug plus TDF/FTC. Supplement: Abstracts of the Tenth International Congress on Drug Therapy in HIV Infection http://www.biomedcentral.com/content/pdf/1758-2652-13-S4-info.pdf Conference: Tenth International Congress on Drug Therapy in HIV Infection 7-11 November 2010 Glasgow, UK (Published: 8 November 2010) doi:10.1186/1758-2652-13-S4-P9 Cite this article as: Billaud et al.: Outcomes in antiretroviral-naive HIVinfected patients initiating therapy with TDF/FTC plus either atazanavir/ r or another third recommended drug. Journal of the International AIDS Society 2010 13(Suppl 4):P9. Full text: PubMed Central: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3113097/
Published: 2010

27. CKD Increases Carbonylation of HDL and Is Associated with Impaired Antiaggregant Properties

Author: Florens, Nans, Calzada, Catherine, Lemoine, Sandrine, Boulet, Marie, Guillot, Nicolas, Barba, Christophe, Roux, Julie, Delolme, Fréderic, Page, Adeline, Poux, Jean, Laville, Maurice, Moulin, Philippe, Soulère, Laurent, Guebre Egziabher, Fitsum, Juillard, Laurent, Soulage, Christophe O, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Department of Nephrology, Transplantation and Clinic Immunology [Hospices civils de Lyon], Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), University of Lyon, ENS de Lyon, Univ. Claude Bernard, Lyon, 69007, France, Association pour l'Utilisation du Rein Artificiel Région Lyonnaise (AURAL), Fédération d’Endocrinologie, Maladies Métaboliques, Diabète et Nutrition, Hôpital Louis Pradel, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), Année Recherche, Agence Régionale de Santé de Rhône Alpes, IRCT – Dialyse, Société Française Néphrologie Dialyse et Transplantation, ITMO Cancer AVIESAN, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherches sur les Macromolécules Végétales (CERMAV), Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), École des Hautes Études en Santé Publique [EHESP] (EHESP), Service Central d'Analyse (SCA), Centre National de la Recherche Scientifique (CNRS), School of Environmental and Life Sciences - SELS (Callaghan, Australia), University of Newcastle [Australia] (UoN), Centre de Recherche en Nutrition Humaine Rhône - Alpes, Chimie Organique et Bioorganique (COB), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), Service de néphrologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Hypoxie : Physiopathologie Respiratoire et Cardiovasculaire (HP2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), SFR Biosciences, École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and CALZADA, Catherine
Subjects: Adult, Blood Platelets, CD36 Antigens, Male, Platelet Aggregation, [SDV]Life Sciences [q-bio], Antibodies, Protein Carbonylation, cardiovascular disease, Malondialdehyde, Animals, Humans, Phosphorylation, Renal Insufficiency, Chronic, Protein Kinase Inhibitors, thrombosis, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, Aldehydes, dyslipidemia, JNK Mitogen-Activated Protein Kinases, nutritional and metabolic diseases, Middle Aged, [SDV] Life Sciences [q-bio], Disease Models, Animal, Oxidative Stress, src-Family Kinases, Basic Research, platelets, dialysis, lipids (amino acids, peptides, and proteins), Female, Rabbits, Lipoproteins, HDL, Oxidation-Reduction, Peritoneal Dialysis, chronic kidney disease
Abstract: International audience; BACKGROUND: CKD is associated with increased oxidative stress that correlates with occurrence of cardiovascular events. Modifications induced by increased oxidative stress particularly affect circulating lipoproteins such as HDL that exhibit antiatheromatous and antithrombotic properties in vitro. METHODS: To explore the specific role of oxidative modifications of HDL in CKD and their effect on the platelet-targeting antiaggregant properties of HDL, we used a CKD (5/6 nephrectomy) rabbit model. For ex vivo assessment of the antiaggregant properties of HDL, we collected blood samples from 15 healthy volunteers, 25 patients on hemodialysis, and 20 on peritoneal dialysis. We analyzed malondialdehyde, 4-hydroxynonenal (HNE), and 4-hydroxy-2-hexenal protein adduct levels. Platelet aggregation and activation were assessed by aggregometry, thromboxane B2 assay, or FACS. We modified HDL from controls by incubating it overnight at 37°C with 100 µM of HNE. RESULTS: HDL from CKD rabbits and patients on hemodialysis had HNE adducts. The percentage of platelet aggregation or activation induced by collagen was significantly higher when platelets were incubated with HDL from CKD rabbit and hemodialysis groups than with HDL from the control group. In both rabbits and humans, platelet aggregation and activation were significantly higher in the presence of HNE-modified HDL than with HDL from their respective controls. Incubation of platelets with a blocking antibody directed against CD36 or with a pharmacologic inhibitor of SRC kinases restored the antiaggregative phenotype in the presence of HDL from CKD rabbits, patients on hemodialysis and peritoneal dialysis, and HNE-modified HDL. CONCLUSIONS: HDL from CKD rabbits and patients on hemodialysis exhibited an impaired ability to inhibit platelet aggregation, suggesting that altered HDL properties may contribute to the increased cardiovascular risk in this population.
Published: 2020

28. Prognostic value for long-term graft survival of estimated glomerular filtration rate and proteinuria quantified at 3 months after kidney transplantation

Author: Georges Mourad, Sophie Girerd, Valérie Garrigue, Luc Frimat, Kevin Duarte, Magali Giral, Jacques Dantal, Michèle Kessler, Marc Ladrière, Fanny Buron, Clément Mottola, Emmanuel Morelon, Nicolas Girerd, Alice Aarnink, Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Laboratoire d'immunologie et d'histocompatibilité, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), RTRS « Centaure », Service de Néphrologie, Dialyse et Transplantation (Hôpital Lapeyronie [Montpellier] CHU), Hôpital Lapeyronie [Montpellier] (CHU), Service de Transplantation, Néphrologie et Immunologie Clinique [Hôpital Edouard Herriot, HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), BOZEC, Erwan, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], and Hospices Civils de Lyon (HCL)
Subjects: medicine.medical_specialty, medicine.medical_treatment, 030232 urology & nephrology, Urology, graft survival, Renal function, kidney transplantation, 030230 surgery, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, delayed graft function, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, medicine, AcademicSubjects/MED00340, Kidney transplantation, Dialysis, Transplantation, Creatinine, Proteinuria, Proportional hazards model, business.industry, creatinine, Original Articles, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, chemistry, Nephrology, ischaemia reperfusion injury, Graft survival, medicine.symptom, proteinuria, business, Validation cohort
Abstract: Background The estimated glomerular filtration rate (eGFR) measured at 1 year is the usual benchmark applied in kidney transplantation (KT). However, acting on earlier eGFR values could help in managing KT during the first post-operative year. We aimed to assess the prognostic value for long-term graft survival of the early (3 months) quantification of eGFR and proteinuria following KT. Methods The 3-, 6- and 12-month eGFR using the Modified Diet in Renal Disease equation (eGFRMDRD) was determined and proteinuria was measured in 754 patients who underwent their first KT between 2000 and 2010 (with a mean follow-up of 8.3 years) in our centre. Adjusted associations with graft survival were estimated using a multivariable Cox model. The predictive accuracy was estimated using the C-index and net reclassification index. These same analyses were measured in a multicentre validation cohort of 1936 patients. Results Both 3-month eGFRMDRD and proteinuria were independent predictors of return to dialysis (all P Conclusion The 3-month eGFR was a valuable predictor of the long-term return to dialysis whose predictive accuracy was not significantly less than that of the 12-month eGFR in multicentre cohorts totalling >2500 patients. Three-month outcomes may be useful in randomized controlled trials targeting early therapeutic interventions.
Published: 2020

29. Impact of age on cardiovascular drug use in patients with chronic kidney disease

Author: Sophie Liabeuf, Marie Metzger, Christian Jacquelinet, Denis Fouque, Ronald L. Pisoni, Luc Frimat, Ziad A. Massy, Cédric Villain, Nicolas Mansencal, Maurice Laville, Serge Briançon, Christian Combe, Bénédicte Stengel, Épidémiologie et recherches translationnelles sur les maladies rénales et cardiovasculaires (EPREC) (U1018 (Équipe 5)), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service Néphrologie/Dialyse [AP-HP Ambroise-Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], CHU Amiens-Picardie, Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Bioingénierie tissulaire (BIOTIS), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de néphrologie, Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Agence de la biomédecine [Saint-Denis la Plaine], Service de Néphrologie [Lyon], Hospices Civils de Lyon (HCL)-Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Arbor Research Collaborative for Health, Service de cardiologie et maladies vasculaires [CHU Ambroise Paré], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Vialaron, Sylvie
Subjects: medicine.medical_specialty, underuse, 030204 cardiovascular system & hematology, elderly, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antithrombotic, Medicine, atrial fibrillation, Stroke, Transplantation, business.industry, Atrial fibrillation, Odds ratio, Original Articles, medicine.disease, stroke, 3. Good health, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Nephrology, Cardiovascular agent, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, 030217 neurology & neurosurgery, Fibrinolytic agent, chronic kidney disease, coronary artery disease, Kidney disease
Abstract: Background Elderly patients with chronic kidney disease (CKD) are often excluded from clinical trials; this may affect their use of essential drugs for cardiovascular complications. We sought to assess the impact of age on cardiovascular drug use in elderly patients with CKD. Methods We used baseline data from the Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort including 3033 adult patients with CKD Stages 3 and 4. We studied the use of recommended drugs for coronary artery disease (CAD), stroke and atrial fibrillation by age, after adjusting for socio-demographic and clinical conditions. Results The patients’ mean age was 66.8 years (mean estimated glomerular filtration rate 32.9 mL/min/1.73 m2). The prevalence of CAD was 24.5% [81.3% receiving antiplatelet agents, 75.6% renin–angiotensin system (RAS) blockers, 65.4% β-blockers and 81.3% lipid-lowering therapy], that of stroke 10.0% (88.8% receiving antithrombotic drugs) and that of atrial fibrillation 11.1% (69.5% receiving oral anticoagulants). Compared with patients aged Conclusions In patients with CKD, older age per se was not associated with the underuse of antithrombotic drugs but was for other major drugs, with a potential impact on cardiovascular outcomes.
Published: 2020

30. Rilpivirine in HIV-1-positive women initiating pregnancy

Author: Frange, Pierre, Tubiana, Roland, Sibiude, Jeanne, Canestri, Ana, Arvieux, Cédric, Brunet-Cartier, Cécile, Cotte, Laurent, Reynes, Jacques, Mandelbrot, Laurent, Warszawski, Josiane, Le Chenadec, Jérôme, Crenn-Hebert, Catherine, Floch-Tudal, Corinne, Mazy, Fabienne, Joras, Marine, Meier, Françoise, Mortier, Emmanuel, Briquet, Catherine, Ichou, Houria, Marty, Laurence, Jabbarian, Hélène, Ceccaldi, Pierre-François, Villemant, Agnès, Zarouk, Virginie, Lefort, Agnès, Ben Salah, Mariam, Hittinger, Gilles, Chamouilli, Jean-Marc, Burle, Christian, Lafeuillade, Alain, Philip, Gisèle, Lambry, Véronique, Medus, Marie, Bachelard, Germaine, Malet, Martine, Dendale-Nguyen, Joëlle, Guimard, Thomas, Guimard, Karine, Brossier, Jean-Pierre, Perre, Philippe, Esnault, Jean-Luc, Aubry, Olivier, Leautez-Nainville, Sophie, Bonnenfant, Valerie, Laine, Laeticia, Martha, Sandrine-Anne, Maurel, Elise, Francoise, Michel, Barat, Muriel, Murger, Patricia, Rouha, Mahfoud, Lévy, Marc, Lumbroso, Philippe, Checoury, Alain, Sahadatu, Osseni, Perfezou, Pascale, Blondin, Gilles, Ansart, Séverine, De Saint Martin, Luc, Le Moine, Philippe, Duthé, Jean-Charles, Daniel, Corinne, Calvez, Christian, Boutaric, Emmanuelle, Rohan, Jennifer, Bauville, Estelle, Dupre, Christelle, Lotton, Pascal, Ouamara-digue, Enora, Poinsignon, Yves, Goussef, Marie, Grelier, Anne, Mousset, Gaetane, Cudeville, Corinne, Niault, Mathilde, Belzic, Isabelle, Moreau, Philippe, Le Coz, Marie-Françoise, Vaillant, Odile Luycx, Guerin-Duplessy, Anne, Mouton-Rioux, Virginie, De Morel, Philippe, Vitrat, Virginie, Tardif, Didier, Gaillat, Jacques, Vanderbergh, Anne, Braig, Suzanne, Clavere, Gaelle, Dehlinger-Paul, Marion, Mohamed, Khaled, Echard, Marie, Camus, Michel, Mulard, Catherine, Fontelonga, Marie-Agnès, Heller-Roussin, Brigitte, Winter, Cécile, Challier, Marion, Debruyne, Elise, Marcou, Valerie, Firtion, Ghislaine, Pannier, Emmanuelle, Costa, Myriam, Launay, Odile, Salmon-Ceron, Dominique, Belkacem, Touria, Bajawi, Youcef, Aubret, Valérie Raynal, Rivaux, Danièle, Elaoun, Neila, Allal, Lahcene, Djoubou, Sandrine, Rahli, Djamila, Moine, Agnès Bourgeois, Valentin, Morgane, Damond, Florence, Huri, Virginie, Vivier, Valérie, Yahia, Fatma Ait, Garrait, Valérie, Hau, Isabelle, Touboul, Claudine, Ratsimbazafy, Lanto, Boiron, Emilie, Elharrar, Brigitte, Labaune, Jean-Marc, Rudigoz, Rene-Charles, Brochier, Corinne, Galvan, Valérie, Ogoudjobi, Stanislas, Elleau, Christophe, Runel-Belliard, Camille, Pistone, Thierry, Fleury, Hervé, Horovitz, Jacques, Sandler, Boris, Roux, Denis, Ragnaud, Jean-Marie, Chabanier, Pierre, Brun, Jean-Luc, Delveaux, Sandrine, Muanza, Blandine, Diallo, Mama Doufari, Lamaury, Isabelle, Sow, Marie-Thérèse, Samar, Ketty, Carpentier, Bénédicte, Osman, Zafer, Dienga, Etienne, Seaume, Hervé, Ducrocq, Sarah, Bailly-Salin, Philippe, Da Silva, Christelle Dusart, Fayolas, Isabelle, Abbal, Julie, Simon-Toulza, Caroline, Truillet, Véronique, Bogner, Noëlle, Chiabrando, Julie, Armand, Evelyne, Cayla, Claudine, Chacé, Anne, Matheron, Isabelle, Richier, Laurent, Miantezila, Joe, Bry, Sandrine, Couderc, Sophie, Narcy, Catherine, Routier, Corinne, Nassar, Rania, Bouldouyre, Marie-Anne, Zakaria, Ahmed, Dauphin, Hélène, Goissen, Céline, Belloy, Marie, Delassus, Jean-Luc, Favret, Véronique, Nemeth, Céline, Partisani, Marialuisa, Entz-Werlé, Natacha, Langer, Bruno, Uettwiller, Françoise, Durand, Myriam, Partizani, MariaLuisa, Cheneau, Christine, Rey, David, Ebel, Edith, Fischer, Patricia, DAVID, Eric, Vayssière, Christophe, Weil, Michèle, Schmitt, Marie Paule, Nisand, Israël, Genet, Philippe, Brault, Dominique, Allisy, Christine, Gerbe, Juliette, Masse, Virginie, Wifaq, Bouchra, Courdavault, Laurence, Gabor, Petra, Tordjeman, Nathalie, Lebrette, Marie-Gisèle, Selleret, Lise, Samama, Déborah, Bolot, Pascal, Khuong-Josses, Marie-Aude, Amel, Mahdi, Bounan, Stéphane, Nourry, Christelle, Andris, Sabine, Blanche, Stephane, Driessen, Marine, Veber, Florence, Fischer, Alain, Rouzioux, Christine, Avettand-Fenoël, Véronique, Mahlaoui, Nizar, Mourey, Marie-Christine, Granier, Michèle, Devidas, Alain, Donnadieu, Anne-Claire, May, Adrien, Chabrol, Amélie, Chevojon, Pierre, Bellahcene, Chahrazede, Sanchez, Audrey, Malbrunot, Claire, Neizelien, Joelle, Agher, Nouara, Pluchart, Claire, Rouger, Christine, Dommergues, Marc, Bonmarchand, Manuela, Shneider, Luminata, Caby, Fabienne, Calin, Ruxandra-Oana, Blanc, Christine, Lupin, Catherine, Pauchard, Michèle, Yangui, Mohamed Amine, Roca, Didier, Todorova, Darina, Laurent, Juliette, Ferry, A., Deschaud, Martine, Blum, Laurent, Chambrin, Véronique, Labrune, Philippe, Clech, Laure, Raho-Moussa, Mariem, Pauly-Ravelly, Isolde, Jault, Thierry, Bouabdallah, Soufiane, Sanchez, Lydie, Sanchez, Anita, Johnson, Ama, Louchard, Agnès, Allouche, Claude, Pathe, Jean-Paul, Lachassine, Eric, Benoist, Laurence, Jeantils, Vincent, Delannoy, Catherine, Benbara, Amélie, Carbillon, Lionel, Borgne, Anne, Moreau, Laurence, PICARD, Fabienne, Karaoui, Leïla, Elbert, Véronique Lefevre, Balaz, Valérie, Bongain, André, Monpoux, Fabrice, Deville, Anne, Galiba, Eliane, Jabbar, Ahmed, Joutel, Martine, Schmidt, Jean-Luc, Decaux, Nathalie, Cravello, Ludovic, Errichiello, Katia, Hubert, Claire, Dollfus, Catherine, Hervé, François, Tabone, Marie-Dominique, Courcoux, Mary-France, Leverger, Guy, Kayem, Gilles, Schnurgier, Aurélie, Jensen, Aurore, Vaudre, Geneviève, Pinquier, Didier, Gromez, Alexis, Pinto-Cardoso, Gaelle, Faye, Albert, Borie, Constance, Levine, Martine, Matheron, Sophie, Marouts, Erianna Bellaton, Boissinot, Christine, Caseris, Marion, Pommelet, Virginie, Morau, Geneviève, Leveille, Sandrine, Boumediene, Marie Astride, Garion, Dominique, Peretti, Delphine, Fourcade, Corinne, Houllier, Marie, Jrad, Ikram, Bourdic, Katia, Monnier, Sylvie, Chirouze, Catherine, Proust, Aurélie, Catteau, Odile, Gardiennet, Quentin, Reliquet, Véronique, Winer, Norbert, Vaucel, Edouard, Rodallec, Audrey, Garnier-André, Elisabeth, Briandet, Claire, Brouard, Jacques, Goubin, Pascale, Beucher, Gaël, Dina, Julia, Demersay, Arnaud Chalvon, Tassi, Sylvie, Lavarenne, Gaelle, Rajguru, Mandovi, Messaoudi, Fabienne, Carré, Nathalie, Rajguru, Mandavi, Bobrie-Moyrand, Claire, Foucaud, Pierre, Bernard, Louis, Maakroun, Zoha, Bourgault, Olivier, Kebaili, Kamila, Bertrand, Yves, Alixe, Véronique, Boyer, Emeline, Billiemaz, Kareen, Fanget, Cécile, Ronat, Véronique, Lesauder, Catherine, Lavastre, Marie Laure, Moulin, Alice, Turquini, Marie-France, Colombani, Dominique, Belgodere, Danièle, Fialaire, Pascale, Proust, Stéphanie, Rehaiem, Sami, Mesnard, Louis, Werner, Evelyne, Dukiel, Nathalie, Desmergers, Baya, Blanc-Ruffat, Isabelle, Maraux, Barbara, Coursol, Anne, Castaneda, Julie, Etienne, Lise, Vintejoux, Emmanuelle, Lalande, Muriel, Segondy, Michel, Guigue, Nelly, De Gennes, Christiane, Clavel, Cyril, Cazassus, François, Walter, Véronique, Mazingue, Françoise, Hammou, Yamina, Lagree, Marion, Paquiez, Odile, D’angelo, Sophie, Boquet, Laurence, Ajana, Faiza, Hatchuel, Yves, Nahri, Imad, Zebelus, Jenny, Genet, Claire, Ducroix-Roubertou, Sophie, Aubrard, Yves, Constanty, Anne, Weinbreck, Pierre, Piet, Emilie, Jacquier, Françoise, Michaud, Christophe, Safwan, Hassan, Boutet, Arnaud, Grand-Courault, Carole, Autret, Fanny, Habibi, Fakher, Azria, Elie, Abdelhadi, Mohamed, Elenga, Narcisse, Bocket, Laurence, Taillet, Françoise, Palenzuela, Gilles, Khadly, Redouane, Pierronnet, Danielle, Dos-Santos, Emmanuelle, David, Selva, Makhloufi, Djamila, Brunel-Dalmas, Florence, Carbonnel-Delalande, Elisabeth, Chiarello, Pierre, Godinot, Matthieu, Gilbert, Sylvie, Massardier, Jérôme, Gauthier-Moulinier, Hélène, Fernandes, Elisabeth, Ranaivojaona, Sata, Chevry, Coralie, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Maladies infectieuses et tropicales [CHU Tenon], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service des maladies infectieuses et réanimation médicale [Rennes] = Infectious Disease and Intensive Care [Rennes], CHU Pontchaillou [Rennes], Centre hospitalier universitaire de Nantes (CHU Nantes), Département de maladies infectieuses, Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Louis Mourier - AP-HP [Colombes], Chirurgie Gynécologique et Obstétrique (CGO), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d'infectiologie [AP-HP Hôpital Louis Mourier, Colombes], Faculté de Médecine Paris-Diderot [Paris], Université Paris Diderot - Paris 7 (UPD7), Service de Médecine Interne [AP-HP, CHU Beaujon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP], Service de médecine interne, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Centre Hospitalier Intercommunal Toulon-La Seyne sur Mer - Hôpital Sainte-Musse, Service de pédiatrie, Centre Hospitalier Chalon-sur-Saône William Morey, CH de Lorient, Laboratoire de Traitement de l'Information Medicale (LaTIM), Université européenne de Bretagne - European University of Brittany (UEB)-Université de Brest (UBO)-Télécom Bretagne-Institut Mines-Télécom [Paris] (IMT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Unité d'hémato-oncologie, CHU Toulouse [Toulouse], Pôle Médico-Chirurgical de Pédiatrie et de Génétique Clinique, Néonatologie, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Service de Gynécologie et Obstétrique [Rennes] = Gynaecology [Rennes], CH Bretagne Sud, Centre d'Investigations Biomédicales - Hématologie - Oncologie - Greffes (CIB-HOG), Centre d'Investigations Biomédicales - Hématologie - Oncologie - Greffes-Hopital St Louis, Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Service des Maladies Infectieuses, Centre Hospitalier de la Région d'Annecy (Pringy), University of Warwick [Coventry], Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Cochin [AP-HP], Université Paris Descartes - Paris 5 (UPD5), Service de Virologie [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Hôpital de la Croix-Rousse [CHU - HCL], Réseau périnatal Aurore, Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), CHU Bordeaux [Bordeaux], pôle gynécologie-obstétrique et médecine foetale, Laboratoire Rhéologie et Procédés (LRP), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Fédération des Maladies Infectieuses [Bordeaux], CHU de Bordeaux Pellegrin [Bordeaux], Centre de compétences des microangiopathies thrombotiques, department of pathology, university hospital, parakou, CHU Pointe-à-Pitre/Abymes [Guadeloupe], Service des Maladies Infectieuses et Tropicales[Point-à-Pitre], Service de Gynécologie-Obstétrique [Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), CHU Strasbourg, Développement et physiopathologie de l'intestin et du pancréas, Institut National de la Santé et de la Recherche Médicale (INSERM), Service de gynécologie–obstétrique, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], CHRU Strasbourg, Département d'échographie et de Médecine fœtale, SIHCUS-CMCO, Service de Gynécologie-Obstétrique, CHI Poissy-Saint-Germain, Centre Hospitalier Victor Dupouy, Service d'informatique médicale et biostatistiques [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Hôpital d'Argenteuil, Centre Hospitalier de Saint-Denis [Ile-de-France], Hôpital Delafontaine, Recherche Epidémiologique en Santé Périnatale et Santé des Femmes et des Enfants (UMR_S 953), Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de microbilogie & unité d'immunologie, hématologie et rhumatologie pédiatriques, Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Chaire Médecine expérimentale (A. Fischer), Collège de France (CdF (institution)), Laboratoire de Virologie [CHU Necker], Université Sorbonne Paris Cité (USPC), IFR Necker-Enfants Malades (IRNEM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Médecine néonatale, Centre Hospitalier Sud Francilien, Service de pneumologie [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Centre Hospitalier Universitaire de Reims (CHU Reims), Service de Gynécologie-Obstétrique, Maternité, Chirurgie Gynécologique [CHU Pitié-Salpêtrière], Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Hôpital Antoine Béclère, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Référence Maladies Héréditaires du Métabolisme Hépatique [Hôpital Antoine Béclère - APHP (CRMR), Service de rhumatologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Service de gynécologie-obstétrique [Hôpital Jean Verdier], Université Paris 13 (UP13)-Hôpital Jean Verdier [AP-HP], Service de Gynécologie-Obstétrique-Reproduction, Hôpital l'Archet, Service d'Hémato-oncologie Pédiatrique [CHU Nice], Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Trousseau [APHP], Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Service des maladies infectieuses et tropicales, Service de pédiatrie générale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Institut Pasteur du Laos, Réseau International des Instituts Pasteur (RIIP), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service de Gynécologie Obstétrique, Service de Médecine Interne et Immunologie clinique [AP-HP Hôpital Bicêtre], Hôpital Bicêtre, Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), service de maladies infectieuses CHU J Minjoz Besancon, Service des maladies infectieuses et tropicales [CHU Nantes], Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de virologie [CHU Nantes], Service de Pédiatrie Enfants - Hématologie Oncologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Pédiatrie Médicale [Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Gynécologie-Obstétrique et Médecine de la Reproduction [CHU Caen], Service de Virologie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Médecine Interne et Maladies Infectieuses [Tours], Service d'hématologie : Immuno-Hématologie pédiatrique et transplantation de moelle osseuse, Hôpital Debrousse, CHU Saint-Etienne, Centre population et développement (CEPED - UMR_D 196), Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), Médecine Néonatale et Réanimation Pédiatrique, CH René Dubos, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service des Maladies Infectieuses et Tropicales [Hôpital Gustave Dron, Tourcoing], Centre Hospitalier Gustave Dron [Tourcoing], 'Personal Protection Against Vectors' working group (PPAV), PPAV working group, Service des Maladies infectieuses et tropicales [CHU Limoges], CHU Limoges, Equipe de Recherche Médicale Appliquée (ERMA), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), CHU Annecy, Service de Pédiatrie, Centre hospitalier de Saint-Nazaire, EA 3593 Université des Antilles et de la Guyane, Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Laboratoire de virologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Service d'immunologie, Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Centre Hospitalier de Basse-Terre, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Université de Rennes (UR), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Collège de France - Chaire Médecine expérimentale (A. Fischer), Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), ANRS CO1/CO11, French national, Viral Hepatitis, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service des maladies infectieuses et tropicales [CHU Tenon], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Université européenne de Bretagne - European University of Brittany (UEB)-Télécom Bretagne-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Mines-Télécom [Paris] (IMT), Hôpital des Enfants, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris-Sud - Paris 11 (UP11), CH Evry-Corbeil-CH Evry-Corbeil, CH Evry-Corbeil, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13), Université Paris Diderot - Paris 7 (UPD7)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Laboratoire d'Electrotechnique de Lyon (LEL), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon, Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Université de Limoges (UNILIM)-CHU Limoges, Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )-Université de Montpellier (UM)
Subjects: rilpivirine, viral suppression, hiv, hiv-1, pregnancy, conception, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, virology
Abstract: International audience; BackgroundSafety data about rilpivirine use during pregnancy remain scarce, and rilpivirine plasma concentrations are reduced during second/third trimesters, with a potential risk of viral breakthroughs. Thus, French guidelines recommend switching to rilpivirine-free combinations (RFCs) during pregnancy.ObjectivesTo describe the characteristics of women initiating pregnancy while on rilpivirine and to compare the outcomes for virologically suppressed subjects continuing rilpivirine until delivery versus switching to an RFC.MethodsIn the ANRS-EPF French Perinatal cohort, we included women on rilpivirine at conception in 2010–18. Pregnancy outcomes were compared between patients continuing versus interrupting rilpivirine. In women with documented viral suppression (
Published: 2020

31. Exposition to glucose-based peritoneal dialysis fluids exacerbates adipocyte lipolysis and glycogen storage in rat adipose cells

Author: Carmen Lab, Team3 Carmen, Christophe Soulage, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Transplantation, Néphrologie et Immunologie Clinique [Hôpital Edouard Herriot, HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Université de Lyon, CarMeN, laboratoire, Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], and Hospices Civils de Lyon (HCL)
Subjects: glucose-based peritoneal dialysis fluid, medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Adipose tissue, White adipose tissue, 030204 cardiovascular system & hematology, Peritoneal dialysis, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, white adipose tissue, Dialysis Solutions, Adipocyte, Internal medicine, Adipocytes, Animals, Humans, Lipolysis, Medicine, Glycogen, business.industry, General Medicine, Rats, [SDV] Life Sciences [q-bio], Glucose, Endocrinology, Basal (medicine), chemistry, peritoneal dialysis, Nephrology, lipolysis, Mannitol, business, medicine.drug
Abstract: International audience; Glucose absorption during peritoneal dialysis (PD) is suspected to promote visceral fat accretion and weight gain in PD patients. The current study was designed to test the impact of glucose-based PD fluids on adipose cell lipolysis and glycogen content. Rat adipose cells, isolated from epididymal fat pad, were exposed to a 30 vol./70 vol. mixture of glucose-based dialysis solutions (containing 1.36% and 3.86% glucose, Physioneal 35®; Baxter) or Krebs-Henseleit buffer for 4 h. Adipose cells were further incubated with laboratory-made solutions containing 1.36% and 3.86% glucose or mannitol as an osmotic control. Baseline and noradrenaline-stimulated lipolysis was measured, and glycogen content assayed. The glucose-based commercial PD fluids as well as the laboratory-manufactured high glucose solutions exacerbated lipolysis in baseline and noradrenaline conditions and increased glycogen stores in adipose cells. Mannitol solutions (1.36% and 3.86%) used as an osmotic control did not produce such effects. This study provides the first evidence that glucose-based dialysis solutions increase basal as well as stimulated lipolysis in adipocytes, an effect that is directly attributable to high concentrations of glucose per se.
Published: 2020

32. Molecular classification of endometrial stromal sarcomas using RNA sequencing defines nosological and prognostic subgroups with different natural history

Author: Marie Karanian, Alexandra Meurgey, Franck Tirode, Pierre Meeus, Isabelle Ray-Coquard, Tatiana Franceschi, Amine Bouhamama, Mehdi Brahmi, Isabelle Treilleux, Armelle Dufresne, Mélodie Carbonnaux, Daniel Pissaloux, Jean-Yves Blay, Hélène Vanacker, Marie-Pierre Sunyach, Département d'Oncologie Médicale [Lyon] ( Centre Léon Bérard), Centre Léon Bérard [Lyon], Service de Pathologie [Centre Leon Berard], Département de Biopathologie, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Département d'anatomopathologie, biopathologie, Département de Radio-Oncologie [CLB, Lyon] (Centre Léon Bérard), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Oncogénèse et progression tumorale, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and TIRODE, Franck
Subjects: 0301 basic medicine, Cancer Research, Stromal cell, sarcoma, RNA-sequencing, [SDV.CAN]Life Sciences [q-bio]/Cancer, Chromosomal rearrangement, Biology, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Prognostic, lcsh:RC254-282, Article, Fusion gene, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Missense mutation, YWHAE, Gene, Endometrial stromal sarcoma, Gene fusions, uterine, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, expression profile, 030104 developmental biology, Oncology, Endometrial stromal sarcomas, 030220 oncology & carcinogenesis, Cancer research, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Sarcoma
Abstract: Simple Summary In about half of the cases, endometrial stromal sarcomas lack the canonical oncogenic fusions JAZF1-SUZ12 or YWHAE-NUTM2, which are mutually exclusive. The aim of this study was to explore by RNA sequencing a retrospective series of uterine sarcomas diagnosed as endometrial stromal sarcomas but negative for JAZF1 and/or YWHAE rearrangement in FISH, in order to provide a better description of their molecular landscape, improve the classification of endometrial stromal sarcomas and provide guidance for disease management. Abstract A series of 42 patient tumors diagnosed as endometrial stromal sarcoma (ESS) based on the morphology but negative for JAZF1 and/or YWHAE rearrangement in FISH was analyzed by RNA-sequencing. A chromosomal rearrangement was identified in 31 (74%) of the cases and a missense mutation in known oncogenes/tumor suppressor genes in 11 (26%). Cluster analyses on the expression profiles from this series together with a control cohort composed of five samples of low grade ESS harboring a JAZF1-SUZ12 fusion, one high grade ESS harboring a BCOR-ITD, two uterine tumors resembling ovarian sex cord tumors, two samples each of uterine leiomyoma and leiomyosarcomas and a series of BCOR-rearranged family of tumor (n = 8) indicated that tumors could be gather in three distinct subgroups: one mainly composed of BCOR-rearranged samples that contained seven ESS samples, one mainly composed of JAZF1-fused ESS (n = 15) and the last composed of various molecular subtypes (n = 19). These three subgroups display different gene signatures, different in silico cell cycle scores and very different clinical presentations, natural history and survival (log-rank test, p = 0.004). While YWHAE-NUTM2 fusion genes may be present in both high and low grade ESS, the high-grade presents with additional BCOR or BCORL1 gene mutations. RNAseq brings clinically relevant molecular classification, enabling the reclassification of diseases and the guidance of therapeutic strategy.
Published: 2020

33. Comparison of longitudinal quality of life outcomes in preemptive and dialyzed patients on waiting list for kidney transplantation

Author: Magali Giral, Myriam Blanchin, Jean-Benoit Hardouin, Emmanuel Morelon, Line Auneau-Enjalbert, Aurélie Meurette, Véronique Sébille, Elisabeth Cassuto, MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Plateforme de Méthodologie et Biostatistique, Direction de la Recherche [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Réseau CENTAURE [Nantes], Université de Nantes (UN)-Institut de Transplantation et de Recherche en Transplantation (ITUN - Institut Transplantation Urologie Néphroplogie*)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Transplantation, Néphrologie et Immunologie Clinique [Hôpital Edouard Herriot, HCL], Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Département de Néphrologie - Hôpital Pasteur [Nice], Hôpital Pasteur [Nice] (CHU), Biostatistique, Recherche Clinique et Mesures Subjectives en Santé, Université de Nantes (UN), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Institut de Transplantation et de Recherche en Transplantation (ITUN - Institut Transplantation Urologie Néphroplogie*), and Le Bihan, Sylvie
Subjects: Adult, Male, Quality of life, Pediatrics, medicine.medical_specialty, Psychometrics, Waiting Lists, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Population, Emotions, Waiting list, Peritoneal dialysis, Kidney transplantation, 03 medical and health sciences, 0302 clinical medicine, Renal Dialysis, Surveys and Questionnaires, Medicine, Humans, Renal replacement therapy, education, Dialysis, education.field_of_study, business.industry, 030503 health policy & services, Public Health, Environmental and Occupational Health, Preemptive, Middle Aged, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Transplantation, 030220 oncology & carcinogenesis, Female, Hemodialysis, 0305 other medical science, business, Peritoneal Dialysis
Abstract: International audience; PURPOSE:The waiting list period for kidney transplantation can be lengthy and associated with a deteriorated health-related quality of life (HRQoL). It might also be experienced differently depending on the experience of renal replacement therapy (preemptive or dialyzed patients), and the type of dialysis. The main objective of this study is to measure and compare HRQoL changes in preemptive, hemodialysis (HD), and peritoneal dialysis (PD) patients during the waiting list period for kidney transplantation.METHODS:A sample of adult patients on kidney transplant waiting list from three French University Hospital centers was recruited. HRQoL was measured using the SF-36 and a specific questionnaire (ReTransQol), which were collected every 6 months before transplantation in preemptive, HD, and PD patients. Mixed-effects models taking into account time and possible confounding factors were used to compare HRQoL changes between the three groups.RESULTS:Preemptive (n = 230), HD (n = 177), and PD patients (n = 39) were enrolled. The renal replacement therapy modalities, time (time on waiting list and age at registration), and gender were associated with HRQoL changes. The HD and PD patients had a significantly lower perceived HRQoL on Role Physical, Social Functioning, and Role Emotional dimensions than the preemptive patients, with lower scores for PD compared to HD patients. The HRQoL scores of all patients were lower compared to the French general population for all dimensions.CONCLUSIONS:A better understanding of pre-transplantation patients' experience can help improving patient care with adapted educational programs and psychological support depending on the type of renal replacement therapy.
Published: 2019

34. Anti-Donor HLA Antibody Response After Pancreatic Islet Grafting: Characteristics, Risk Factors, and Impact on Graft Function

Author: Pouliquen, Eric, Baltzinger, P., Lemle, A., Chen, Chien-Chia, Parissiadis, A., Borot, S., Frimat, L., Girerd, S., Berney, T., Lablanche, S., Benhamou, P. Y., Morelon, E., Badet, L., Dubois, V., Kessler, L., Thaunat, Olivier, Network, Gragil, Service de Transplantation, Néphrologie et Immunologie Clinique [Hôpital Edouard Herriot, HCL], Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Lymphocytes B effecteurs et à mémoire – Effector and memory B cells, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Endocrinologie - Diabète et Maladies Métaboliques, Hôpitaux Universitaires de Strasbourg, Etablissement Français du Sang - Grand Est (EFS - alsace strasbourg), Service de Diabétologie - Endocrinologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Department of Surgery, University of Geneva [Switzerland], Service d'Endocrinologie, Pôle Digidune, CHU Grenoble, Service d'Urologie et Chirurgie de la Transplantation, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Etablissement français du sang- Rhône-Alpes [Lyon], Université de Lyon, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Service de diabétologie - endocrinologie, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, CHU Strasbourg, Geneva University Hospital (HUG), Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée [2016-2019] (LBFA [2016-2019]), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre Hospitalier Universitaire [Grenoble] (CHU), Service d'urologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), EFS de Lyon, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Genève = University of Geneva (UNIGE)
Subjects: Graft Rejection, Male, antibody-mediated (ABMR) [rejection], [SDV]Life Sciences [q-bio], medicine.medical_treatment, Islets of Langerhans Transplantation, 030232 urology & nephrology, 030230 surgery, Postoperative Complications, 0302 clinical medicine, HLA Antigens, Risk Factors, Isoantibodies, Immunology and Allergy, Pharmacology (medical), Longitudinal Studies, ComputingMilieux_MISCELLANEOUS, Sensitization, geography.geographical_feature_category, ddc:617, biology, Graft Survival, Middle Aged, Prognosis, Islet, Tissue Donors, 3. Good health, medicine.anatomical_structure, Immunosuppressive drug, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Antibody, Type 1, Adult, Human leukocyte antigen, clinical research/practice, 03 medical and health sciences, Diabetes mellitus, Diabetes Mellitus, alloantibody, medicine, Humans, Retrospective Studies, Transplantation, geography, business.industry, islet transplantation, Insulin, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Transplant Recipients, body regions, rejection: antibody-mediated (ABMR), Immunology, biology.protein, business, Follow-Up Studies
Abstract: International audience; Pancreatic islet grafting restores endogenous insulin production in type 1 diabetic patients, but long-term outcomes remain disappointing as a result of immunological destruction of allogeneic islets. In solid organ transplantation, donor-specific anti-HLA antibodies (DSA) are the first cause of organ failure. This retrospective multicentric study aimed at providing in-depth characterization of DSA response after pancreatic islet grafting, identifying the risk factor for DSA generation and determining the impact of DSA on graft function. Forty-two pancreatic islet graft recipients from the Groupe Rhin-Rhône-Alpes-Genève pour la Greffe d'Ilots de Langerhans consortium were enrolled. Pre- and postgrafting sera were screened for the presence of DSA and their ability to activate complement. Prevalence of DSA was 25% at 3 years postgrafting. The risk of sensitization increased steeply after immunosuppressive drug withdrawal. DSA repertoire diversity correlated with the number of HLA and eplet mismatches. DSA titer was significantly lower from that observed in solid organ transplantation. No detected DSA bound the complement fraction C3d. Finally, in contrast with solid organ transplantation, DSA did not seem to negatively affect pancreatic islet graft survival. This might be due to the low DSA titers, specific features of IgG limiting their ability to activate the complement and/or the lack of allogenic endothelial targets in pancreatic islet grafts.
Published: 2017

35. Exome sequencing in Hereditary Hypophosphatemic Rickets

Author: Gaisne, Raphaël, Figueres, Lucile, Houillier, Pascal, Vargas-Poussou, Rosa, Lemoine, Sandrine, Leman, Claire, Vince, Nicolas, Gourraud, Pierre-Antoine, Limou, Sophie, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Regenerative Medicine and Skeleton research lab (RMeS), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité des maladies rénales et métaboliques [Hôpital Européen Georges-Pompidou - APHP], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Génétique [CHU HEGP], Service de Transplantation, Néphrologie et Immunologie Clinique [Hôpital Edouard Herriot, HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), École Centrale de Nantes (ECN), Regenerative Medicine and Skeleton (RMeS), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), and Le Bihan, Sylvie
Subjects: [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience
Published: 2019

36. The 1-year Renal Biopsy Index: a scoring system to drive biopsy indication at 1-year post-kidney transplantation

Author: Dany Anglicheau, Grégoire Couvrat-Desvergnes, Magali Giral, Chloé Paul, Emmanuel Morelon, Sophie Brouard, Maarten Naesens, Karine Renaudin, Redmer Luning, Alexandre Huneau, Etienne Dantan, Yohann Foucher, Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Immunoregulation And Immunointervention in Transplantation and Autoimmunity (Team 4 - U1064 Inserm - CRTI), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Anatomo-cyto-pathologie [Hôtel-Dieu, Nantes], Hôtel-Dieu de Nantes, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University Hospitals Leuven [Leuven], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Réseau CENTAURE, Department of Nephrology, Transplantation and Clinic Immunology [Hospices civils de Lyon], Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Service de Néphrologie, dialyse, transplantation [CHD Vendée] (Site de La Roche sur Yon), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Centre hospitalier universitaire de Nantes (CHU Nantes), The Roche Pharma, Novartis, and Sanoﬁ laboratories ., ANR-11-JSV1-0008,CSM (Composite Surrogate Marker),Construction d'un marqueur composite de substitution de la survie à long terme : application à la transplantation rénale(2011), Le Bihan, Sylvie, Jeunes Chercheuses et Jeunes Chercheurs - Construction d'un marqueur composite de substitution de la survie à long terme : application à la transplantation rénale - - CSM (Composite Surrogate Marker)2011 - ANR-11-JSV1-0008 - JCJC - VALID, Kidney Transplant Center [CHU Necker], Université Paris Descartes - Paris 5 (UPD5)-Sorbonne Université (SU)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Départemental Vendée, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Université Paris Descartes - Paris 5 (UPD5), and Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques
Subjects: medicine.medical_specialty, 030232 urology & nephrology, Urology, kidney transplantation, 030230 surgery, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Biopsy, Medicine, Kidney transplantation, Transplantation, Creatinine, Kidney, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, medicine.diagnostic_test, histological diagnostic, business.industry, Histology, predictive score, medicine.disease, 3. Good health, medicine.anatomical_structure, chemistry, Cohort, surveillance biopsy, Renal biopsy, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Surveillance biopsies after renal transplantation remain debatable. To drive the decision of such intervention, we propose a predictive score of abnormal histology at 1-year post-transplantation, named 1-year Renal Biopsy Index (1-RBI). We studied 466 kidney recipients from the DIVAT cohort alive with a functioning graft and a surveillance biopsy at 1-year post-transplantation. Patients displaying abnormal histology (49%) (borderline, acute rejection, interstitial fibrosis and tubular atrophy [IFTA] grade 2 or 3, glomerulonephritis) were compared to the normal or subnormal (IFTA grade 1) histology group. Obtained from a lasso penalized logistic regression , the 1-RBI was composed of recipient gender, serum creatinine at 3, 6, and 12 month post-transplantation and anticlass II immunization at transplantation (internal validation: AUC = 0.71, 95% CI [0.53-0.83]; external validation: AUC = 0.62, 95% CI [0.58-0.66]). While we could not determinate a threshold able to identify patients at high chance of normal or subnormal histology, we estimated and validated a discriminating threshold capable of identifying a subgroup of 15% of the patients with a risk of abnormal histology higher than 80%. The 1-RBI is computable online at www.divat.fr. The 1-RBI could be a useful tool to standardize 1-year biopsy proposal and may for instance help to indicate one in case of high risk of abnormal histology.
Published: 2019

37. Lack of impact of pre-emptive deceased-donor kidney transplantation on graft outcomes: a propensity score-based study

Author: Magali Giral, Marc Ladrière, Sophie Girerd, Christophe Legendre, Laetitia Albano, Fanny Buron, Denis Glotz, Valérie Garrigue, Florent Le Borgne, Emmanuel Morelon, Carmen Lefaucheur, Yohann Foucher, Georges Mourad, Elisabeth Cassuto, MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Centre hospitalier universitaire de Nantes (CHU Nantes), IDBC/A2com [Pace, France], Réseau CENTAURE, Département de Néphrologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hospices Civils de Lyon (HCL), Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de transplantation rénale [CHRU Nancy], Centre Hospitalier Universitaire de Nancy (CHU Nancy), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Ecotaxie, microenvironnement et développement lymphocytaire (EMily (UMR_S_1160 / U1160)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital Saint-Louis [AP-HP] (AP-HP), Hôpital Pasteur [Nice] (CHU), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Immunoregulation And Immunointervention in Transplantation and Autoimmunity (Team 4 - U1064 Inserm - CRTI), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Le Bihan, Sylvie, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Kidney Transplant Center [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Université Paris Descartes - Paris 5 (UPD5), Department of Nephrology, Transplantation and Clinic Immunology [Hospices civils de Lyon], Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Service de Néphrologie, Dialyse et Transplantation (Hôpital Lapeyronie [Montpellier] CHU), Hôpital Lapeyronie [Montpellier] (CHU), Paris Translational Research Center for Organ Transplantation & Department of Nephrology and Transplantation, Université Paris Diderot - Paris 7 (UPD7)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de néphrologie et transplantation rénale [Nice], and Université Paris Descartes - Paris 5 (UPD5)-Sorbonne Université (SU)-CHU Necker - Enfants Malades [AP-HP]
Subjects: Male, medicine.medical_specialty, Time Factors, Waiting Lists, medicine.medical_treatment, 030232 urology & nephrology, 030204 cardiovascular system & hematology, patient and graft survival, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 03 medical and health sciences, 0302 clinical medicine, Renal Dialysis, Risk Factors, Internal medicine, medicine, Humans, Renal replacement therapy, Prospective Studies, causal inference, Propensity Score, Dialysis, Kidney transplantation, Transplantation, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Graft Survival, pre-emptive kidney transplantation, Middle Aged, medicine.disease, Kidney Transplantation, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Tissue Donors, 3. Good health, Treatment Outcome, Nephrology, Cohort, Propensity score matching, Kidney Failure, Chronic, dialysis, Observational study, Female, observational study, Hemodialysis, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Follow-Up Studies
Abstract: International audience; BACKGROUND: A significant number of studies have compared graft outcomes between patients with Pre-emptive Kidney Transplantation (PreKT) and patients on Dialysis before their Kidney Transplantation (DiaKT). These studies have suffered from the limitation that the DiaKT group is composed of all the dialysed patients, including those placed on a waiting list at the time of their first dialysis session. This seriously questions the comparability of these patients with those placed on the waiting list a long time before the need for renal replacement therapy. The aim of this study was to precisely evaluate the causal effect of PreKT from deceased donors.METHODS: Data were extracted from the multicentric French DIVAT (Données Informatisées et VAlidées en Transplantation) cohort. The DiaKT group was composed of patients placed on the waiting list with an initial intention of pre-emptive transplantation. Cause-specific Cox models with propensity scores (inverse probability weighting) were used to study the patient and graft outcomes.RESULTS: Among the 1138 included patients, 554 patients were in the PreKT group. The outcomes of the PreKT group were similar compared with the DiaKT group. In particular, the life expectancy with a functioning graft was 8.51 years [95% confidence interval (CI) 8.20-8.81] for the PreKT recipients versus 8.49 years (95% CI 8.15-8.84) for the DiaKT recipients.CONCLUSIONS: Our results challenge the utility of PreKTs from deceased donors, especially with regard to the consequential increase in the waiting list.
Published: 2019

38. UMD-MEN1 database: an overview of the 370 MEN1 variants present in 1,676 patients from the French population

Author: Pierre Goudet, Alain Calender, Pauline Romanet, Marie-Françoise Odou, Anne Barlier, Celine Guien, Lucie Coppin, Marie-Odile North, Françoise Borson-Chazot, Christophe Béroud, Eric Pasmant, Amira Mohamed, S. Giraud, Morgane Pertuit, Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance Publique - Hôpitaux de Marseille (APHM), Laboratoire de Génétique, Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre de biologie pathologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Genetique et Biotherapies des Maladies Degeneratives et Proliferatives du Systeme Nerveux (Inserm U745), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de médecine nucléaire, Groupement Hospitalier Lyon-Est (GHE), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Fédération d'endocrinologie, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Cochin [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche Jean-Pierre Aubert-Neurosciences et Cancer, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Fédération d'endocrinologie-Groupement hospitalier Lyon-Est, Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille
Subjects: 0301 basic medicine, Male, endocrine system diseases, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Penetrance, computer.software_genre, Biochemistry, French population, 0302 clinical medicine, Endocrinology, Multiple endocrine neoplasia, Child, Databases, Protein, Aged, 80 and over, education.field_of_study, medicine.diagnostic_test, Database, Hyperparathyroidism, Multiple Endocrine Neoplasia, Age Factors, Autosomal dominant trait, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Child, Preschool, Female, Mutation Analysis, France, Neuroendocrine tumors, Adult, endocrine system, Adolescent, Genotype, Genetic counseling, Population, 030209 endocrinology & metabolism, Context (language use), 03 medical and health sciences, Young Adult, Proto-Oncogene Proteins, medicine, Multiple Endocrine Neoplasia Type 1, Humans, Genetic Testing, education, Genetic testing, Aged, business.industry, Biochemistry (medical), Infant, Newborn, Infant, Odds ratio, medicine.disease, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Mutation, business, computer
Abstract: Context Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disease caused by mutations in the MEN1 gene characterized by a broad spectrum of clinical manifestations, of which the most frequent are primary hyperparathyroidism, pituitary adenomas, and neuroendocrine tumors. Objective The aim of this work was to facilitate interpretation of variants and improve the genetic counseling and medical care of families of patients with MEN1. Design, Setting, and Patients The TENGEN network (Oncogenetics Network of Neuroendocrine Tumors) has interpreted and collected all allelic variants and clinical characteristics of the MEN1-positive patients identified through genetic testing performed in the French population from 1997 to 2015. Patients and their variants were registered in the locus-specific UMD-MEN1 database (www.umd.be/MEN1/). Main Outcomes Variant classification, age-related penetrance, and odds ratios. Results A total of 370 distinct variants reported in 1676 patients, including 181 unpublished variants, have been registered. This database analysis revealed a low frequency (6.6%) of benign or likely benign missense variants in MEN1. Eight families (1.9%) had members with familial isolated hyperparathyroidism and harbored the same mutations as that found in families with authentic MEN1. An association existed between large rearrangements and an earlier onset of the disease, whereas no difference was observed between truncating and nontruncating variants. Conclusion The UMD-MEN1 database provides an exhaustive overview of the MEN1 variants present in the French population. For each variant, a classification is publicly available. Clinical data collections allow the determination of genotype-phenotype correlation and age-related penetrance of lesions in the cohort.
Published: 2019

39. Missing self triggers NK cell-mediated chronic vascular rejection of solid organ transplants

Author: Vannary Meas-Yedid, Sébastien Dussurgey, Thomas Barba, Emmanuel Morelon, Maud Rabeyrin, Romain Guillemain, Maud Racapé, Jean-Paul Duong-Van-Huyen, Valérie Dubois, Chien-Chia Chen, Antoine Marçais, Stéphanie Ducreux, Jean-Christophe Olivo-Marin, Maarten Naesens, Jean-Luc Taupin, Antoine Sicard, Antonino Nicoletti, Olivier Thaunat, Patrick Bruneval, Béatrice Charreau, Helena Paidassi, Alice Koenig, Virginie Mathias, Alexandre Loupy, Thierry Walzer, Thierry Defrance, Jasper Callemeyn, Paidassi, Helena, Instituts Hospitalo-Universitaires B - Organ ProtEction and ReplAcement - - OPeRa2010 - ANR-10-IBHU-0004 - IBHU - VALID, Phenotypage pour le cancer - - PHENOCAN2011 - ANR-11-EQPX-0035 - EQPX - VALID, Ciblage de PECAM-1 pour la prévention et le traitement du rejet humoral en transplantation d'organe - - PETTAR2016 - ANR-16-CE17-0007 - AAPG2016 - VALID, Lymphocytes B effecteurs et à mémoire – Effector and memory B cells, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Transplantation, Néphrologie et Immunologie Clinique [Hôpital Edouard Herriot, HCL], Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Réponse immunitaire innée dans les maladies infectieuses et auto-immunes – Innate immunity in infectious and autoimmune diseases, Laboratoire HLA [EFS - Auvergne-Rhônes-Alpes], Etablissement français du sang - Auvergne-Rhône-Alpes (EFS), Departement de Pathologie [Hospices civils de Lyon], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), SFR Biosciences, Analyse d'images biologiques - Biological Image Analysis (BIA), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Ecotaxie, microenvironnement et développement lymphocytaire (EMily (UMR_S_1160 / U1160)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'immunologie, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University Hospitals Leuven [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), O.T. is supported by the Agence nationale pour la Recherche (ANR-16-CE17-0007-01), the Fondation pour la Recherche médicale (PME20180639518), and the Etablissement français du Sang. C.-C.C., E.M. and O.T. are supported by the Institut Hospitalo-Universitaire–Organ Protection and Replacement (IHU-OPeRa, ANR-10-IBHU-004). A.K. is supported by INSERM (poste accueil 2015/1239/BT), the Hospices Civils de Lyon and the Fondation du Rein. SFR Biosciences is supported by the Agence nationale pour la Recherche (ANR -11-EQPX-0035 PHENOCAN). E.M. and O.T. are members of the CENTAURE Transplantation Research Network., We thank Christelle Forcet and Violaine Tribollet for help with Xcelligence experiments, and Marie-Claude Gagnieu and Laurent Genestier for fruitful scientific discussions. The authors thank Mathilde Koenig for her contribution to the design of the figure., ANR-10-IBHU-0004,OPeRa,Organ ProtEction and ReplAcement(2010), ANR-11-EQPX-0035,PHENOCAN,Phenotypage pour le cancer(2011), ANR-16-CE17-0007,PETTAR,Ciblage de PECAM-1 pour la prévention et le traitement du rejet humoral en transplantation d'organe(2016), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Graft Rejection, 0301 basic medicine, Cell, Translational immunology, General Physics and Astronomy, Inflammatory diseases, 030230 surgery, 0302 clinical medicine, Receptors, KIR, lcsh:Science, Receptor, Cells, Cultured, Mice, Knockout, Multidisciplinary, medicine.diagnostic_test, biology, Tissue Donors, 3. Good health, Killer Cells, Natural, medicine.anatomical_structure, [SDV.IMM]Life Sciences [q-bio]/Immunology, Antibody, [SDV.IMM] Life Sciences [q-bio]/Immunology, Science, Human leukocyte antigen, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Biopsy, Homologous chromosome, medicine, Animals, Humans, Transplantation, Homologous, Inflammation, business.industry, Endothelial Cells, General Chemistry, Innate immune cells, Mice, Inbred C57BL, Transplantation, 030104 developmental biology, Microvessels, Immunology, biology.protein, Heart Transplantation, lcsh:Q, K562 Cells, beta 2-Microglobulin, business, K562 cells
Abstract: Current doctrine is that microvascular inflammation (MVI) triggered by a transplant -recipient antibody response against alloantigens (antibody-mediated rejection) is the main cause of graft failure. Here, we show that histological lesions are not mediated by antibodies in approximately half the participants in a cohort of 129 renal recipients with MVI on graft biopsy. Genetic analysis of these patients shows a higher prevalence of mismatches between donor HLA I and recipient inhibitory killer cell immunoglobulin-like receptors (KIRs). Human in vitro models and transplantation of β2-microglobulin-deficient hearts into wild-type mice demonstrates that the inability of graft endothelial cells to provide HLA I-mediated inhibitory signals to recipient circulating NK cells triggers their activation, which in turn promotes endothelial damage. Missing self-induced NK cell activation is mTORC1-dependent and the mTOR inhibitor rapamycin can prevent the development of this type of chronic vascular rejection., ‘Missing self’ is a mode of natural killer (NK) cell activation aimed to detect the lack of HLA-I molecules on infected or neoplastic cells. Here, the authors show that mismatch between donor HLA-I and cognate receptors on recipient NK cells mediates microvascular inflammation-associated graft rejection, a pathology that is preventable by mTOR inhibition.
Published: 2019

40. Natural killer cell infiltration is discriminative for antibody-mediated rejection and predicts outcome after kidney transplantation

Author: Dirk Kuypers, Evelyne Lerut, Pierre Marquet, Henriette de Loor, Wilfried Gwinner, Marie Essig, Stéphane Gazut, Frans Schuit, Dany Anglicheau, Jasper Callemeyn, Carole Saison, Leentje Van Lommel, Saleh Yazdani, Olivier Thaunat, Max Wevers, Ben Sprangers, Lieven Thorrez, Alice Koenig, Maarten Naesens, Line Heylen, Laure-Hélène Noël, Department of Nephrology and Renal Transplantation, University Hospitals Leuven [Leuven]-Catholic University Leuven, Laboratoire d'analyse des données et d'intelligence des systèmes (LADIS), Département Métrologie Instrumentation & Information (DM2I), Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, University Hospitals Leuven [Leuven], Lymphocytes B effecteurs et à mémoire – Effector and memory B cells, Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Service de Transplantation, Néphrologie et Immunologie Clinique [Hôpital Edouard Herriot, HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Gene Expression Unit, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Service de Néphrologie, Dialyse, Transplantations [CHU Limoges], CHU Limoges, Hannover Medical School [Hannover] (MHH), Département de Néphrologie [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), European Project: 305499,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,BIOMARGIN(2013), Laboratoire d'Intégration des Systèmes et des Technologies (LIST (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Laboratoire d'Intégration des Systèmes et des Technologies (LIST (CEA)), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ESSIG, Marie, and Biomarkers of renal graft injuries in kidney allograft recipients - BIOMARGIN - - EC:FP7:HEALTH2013-03-01 - 2017-02-28 - 305499 - VALID
Subjects: 0301 basic medicine, Graft Rejection, Male, Biopsy, Cell, 030232 urology & nephrology, Datasets as Topic, Kidney, Transcriptome, 0302 clinical medicine, Cytotoxic T cell, Kidney transplantation, Oligonucleotide Array Sequence Analysis, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], natural killer cells, Middle Aged, Allografts, Prognosis, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, Killer Cells, Natural, medicine.anatomical_structure, Treatment Outcome, Nephrology, antibody-mediated rejection, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, Infiltration (medical), Adult, Cell type, kidney transplantation, survival, Antibodies, Natural killer cell, histology, 03 medical and health sciences, Young Adult, Immune system, Predictive Value of Tests, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Humans, Aged, business.industry, Gene Expression Profiling, Computational Biology, kid- ney transplantation, medicine.disease, 030104 developmental biology, Case-Control Studies, Immunology, gene expression, Kidney Failure, Chronic, business, Biomarkers
Abstract: Despite partial elucidation of the pathophysiology of antibody-mediated rejection (ABMR) after kidney transplantation, it remains largely unclear which of the involved immune cell types determine disease activity and outcome. We used microarray transcriptomic data from a case-control study (n=95) to identify genes that are differentially expressed in ABMR. Given the co-occurrence of ABMR and T-cell-mediated rejection (TCMR), we built a bioinformatics pipeline to distinguish ABMR-specific mRNA markers. Differential expression of 503 unique genes was identified in ABMR, with significant enrichment of natural killer (NK) cell pathways. CIBERSORT (Cell type Identification By Estimating Relative Subsets Of known RNA Transcripts) deconvolution analysis was performed to elucidate the corresponding cell subtypes and showed increased NK cell infiltration in ABMR in comparison to TCMR and normal biopsies. Other leukocyte types (including monocytes/macrophages, CD4 and CD8 T cells, and dendritic cells) were increased in rejection, but could not discriminate ABMR from TCMR. Deconvolution-based estimation of NK cell infiltration was validated using computerized morphometry, and specifically associated with glomerulitis and peritubular capillaritis. In an external data set of kidney transplant biopsies, activated NK cell infiltration best predicted graft failure amongst all immune cell subtypes and even outperformed a histologic diagnosis of acute rejection. These data suggest that NK cells play a central role in the pathophysiology of ABMR and graft failure after kidney transplantation. ispartof: Kidney International vol:95 issue:1 pages:188-198 ispartof: location:United States status: published
Published: 2019

41. Impact of active oxygenation and oxygen carrier during the kidney transplant preservation in machine perfusion before transplantation

Author: KASIL, Abdelsalam, Service d'urologie, Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Poitiers (France), Thierry Hauet, Lionel Badet et Céline Auxenfans., and KASIL, Abdelsalam
Subjects: Oxygénation active, Transplantation, Hémoglobine, M101, Donneurs marginaux, Marginal donors, Machine perfusion WAVES®, [SDV]Life Sciences [q-bio], Transporteur d'oxygène, Active oxygenation, [SDV] Life Sciences [q-bio], Kidney transplantation, Ischémie-Reperfusion, Lésions d'ischémie-reperfusion, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Dcd, Transplantation rénale, Rein, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Oxygen carrier, Dons d'organes, Ischemia-Reperfusion
Abstract: Introduction: It is proved that preservation of marginal kidney graft in machine perfusion (MP) is beneficial. However, this method requires improvement to minimize the ischemia-reperfusion injuries (IRI), as addition of oxygen and/or an oxygen carrier. We aimed to evaluate the effects of oxygenation (100% or 21%) and the addition of marine worm hemoglobin (HbAm, M101) during hypothermic renal perfusion before transplantation. Our endpoints were based on graft function recovery and late renal dysfunction. Method and materials: We use a porcine model where kidneys were submitted to 1h warm ischemia, followed by WAVES® MP preservation for 23h before auto-transplantation. Four groups were studied: W (MP-21% O2), W-O2 (MP-100% O2), W-M101 (MP-21% O2 + 2g/L HbAm), W-O2+M101 (100% O2 + 2g/L HbAm), (n=6 per group). Results: Kidneys preserved in W-M101 group showed a higher perfusion flow and lower renal resistance, compared to other groups. During the first week post-transplantation, W-O2 or W-M101 groups showed lower blood creatinine and better glomerular filtration rate. Blood levels of KIM-1 and IL-18 were lower in W-M101 group, while blood levels of AST and NGAL were lower in groups with 100% O2. Three months after transplantation, the fractional excretion of sodium and the proteinuria/ creatininuria ratio were higher in W group. Blood creatinine was lower in W-M101 group. Interstitial fibrosis evaluated at 3 months was lower in groups W-M101 and W-O2+M101. We showed that the combination 21% O2 + hemoglobin improves the kidney graft outcome.Conclusion: We showed that the combination of 21% O2 + hemoglobin improved the kidney graft outcome., Il est prouvé que la conservation des greffons rénaux marginaux en machine de perfusion (MP) est bénéfique. Cependant, cette méthode nécessite des améliorations afin de minimiser les lésions d’ischémie-reperfusion (I/R), par l’ajout d’oxygène et/ou d’un transporteur d’oxygène. Nous avons cherché à évaluer les effets de l’oxygénation et de l’ajout d’une hémoglobine de ver marin (HbAm, M101) durant la perfusion rénale hypothermique avant transplantation. Nos critères de jugement étaient basés sur la reprise de fonction du greffon et sur les lésions tardives de dysfonction rénale. Nous avons utilisé un modèle porcin : les reins ont été exposés à 1h d’ischémie chaude, puis perfusés dans une MP WAVES® pendant 23h à 4°C avant autotransplantation. Quatre groupes ont étudié : W (MP-21% O2), W-O2 (MP-100% O2), W-M101 (MP-21% O2 + 2g/L HbAm), W-O2+M101 (100% O2 + 2g/L HbAm), (n=6 per groupe). Les reins du groupe W-M101 ont montré un débit de perfusion plus élevé et une résistance rénale plus faible comparé aux autres groupes. Pendant la première semaine post-transplantation, les groupes W-O2 et W-M101 ont montré une créatininémie significativement plus faible et un meilleur taux de filtration glomérulaire (GFR). Les niveaux circulants de KIM-1 et IL-18 étaient plus faibles dans le groupe W-M101, tandis que les niveaux de NGAL et d’ASAT étaient plus faibles dans les groupes d’oxygénation active. Trois mois post-transplantation, la fraction excrétée de sodium et le ratio protéinurie/créatininurie étaient plus élevé dans le groupe W. La créatininémie était plus faible dans le groupe W-M101. La fibrose interstitielle a évalué à 3 mois post-transplantation étaient plus faible dans les groupes W-M101 et W-O2+M101. Nous avons révélé histologiquement que l’infiltration de mastocytes était significativement élevée dans le groupe W comparé aux autres groupes. Nous avons montré que la combinaison de 21% O2 + hémoglobine améliorent la reprise de fonction du greffon rénale.
Published: 2018

42. Chronic Rejection in Human Vascularized Composite Allotransplantation (Hand and Face Recipients)

Author: Olivier Thaunat, Sylvie Testelin, Lionel Badet, J. Kanitakis, Jean-Michel Dubernard, Bernard Devauchelle, Emmanuel Morelon, Aram Gazarian, Palmina Petruzzo, Clinique Dermatologique, Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Service d'Urologie et Chirurgie de la Transplantation, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Department of Medical Sciences, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Clinique du Parc, Lymphocytes B effecteurs et à mémoire – Effector and memory B cells, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Transplantation, Néphrologie et Immunologie Clinique [Hôpital Edouard Herriot, HCL], CHU Amiens-Picardie, CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 (CHIMERE), Université de Picardie Jules Verne (UPJV), and Département de chirurgie maxillofaciale et stomatologie [CHU d'Amiens-Picardie]
Subjects: Graft Rejection, Vascularized Composite Allotransplantation, Transplantation, medicine.medical_specialty, Graft acceptance, business.industry, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Immunosuppression, 030230 surgery, medicine.disease, Surgery, 03 medical and health sciences, 0302 clinical medicine, Vascular narrowing, Atrophy, Deep tissue, Chronic Disease, medicine, Humans, 030211 gastroenterology & hepatology, Composite tissue, business, Immune mechanisms
Abstract: International audience; Vascularized composite tissue allografts (VCA) have become a viable option to restore severely damaged parts of the body that cannot be repaired with conventional surgical techniques. Acute rejection develops frequently in the early postgraft period both in human and experimental VCA, but the possibility of human VCA to undergo chronic rejection (CR) remained initially unknown. The experience gained over the years shows that, similar to solid organ transplants (SOT), human VCA can also develop CR. Chronic rejection is clinically mostly apparent on the skin and targets preferentially skin and deep vessels, leading, as in SOT, to graft vasculopathy and often to graft loss. Dermal sclerosis and adnexal atrophy are additional features of CR. The pathogenetic immune mechanisms involved (cell-mediated versus humoral) remain incompletely known. The changes of CR can be detected with skin and deep tissue biopsies. Modern in vivo imaging tools can detect vascular narrowing and have the advantage of being noninvasive. However, the diagnosis and treatment of CR remain challenging, as several important questions remain to be answered: a more accurate definition of CR in VCA is needed to establish criteria allowing an accurate and early diagnosis. The pathogenetic mechanisms of CR need to be better understood to allow more efficacious treatment. Favoring/triggering factors of CR need to be better known so that they can be avoided. As in SOT, there is a need for efficient tolerance-inducing protocols that will favor graft acceptance and (ideally) circumvent the necessity of lifelong immunosuppression.
Published: 2016

43. Clinicopathological Findings of Chronic Rejection in a Face Grafted Patient

Author: Fanny Buron, Emmanuel Morelon, Jean Baptiste Pialat, Palmina Petruzzo, Sylvie Testelin, Lionel Badet, Olivier Thaunat, Bernard Devauchelle, Jean Kanitakis, Service de Transplantation, Néphrologie et Immunologie Clinique [Hôpital Edouard Herriot, HCL], Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Department of Medical Sciences, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Département de Dermatologie [CH Lyon-Sud, Pierre-Bénite], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Département de chirurgie maxillofaciale et stomatologie [CHU d'Amiens-Picardie], CHU Amiens-Picardie, Service de Radiologie, Lymphocytes B effecteurs et à mémoire – Effector and memory B cells, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Graft Rejection, Male, Pathology, medicine.medical_specialty, Erythema, Biopsy, medicine.medical_treatment, Asymptomatic, Vascularized Composite Allotransplantation, medicine, Humans, Hypopigmentation, Transplantation, Facial Transplantation, business.industry, Graft Survival, Immunosuppression, Allografts, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Tacrolimus, 3. Good health, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Chronic Disease, [SDV.IMM]Life Sciences [q-bio]/Immunology, medicine.symptom, business, Immunosuppressive Agents
Abstract: International audience; BACKGROUND: Skin chronic rejection (CR) in vascularized composite allotransplantation has not been included in the Banff classification yet. We report a face-transplant patient who developed cutaneous clinicopathologic changes suggestive of CR. METHODS: The recipient was a 27-year-old man with severe disfigurement of the lower face due to a pyrotechnic explosion. He received a facial allograft, including mandible, cheeks, lips, and chin, in November 2009. Immunosuppression included antithymocyte globulins and bone-marrow infusion then steroids, tacrolimus, and mycophenolate mofetil. RESULTS: During the first posttransplant year the acute rejection episodes were characterized by reversible oedema and erythema of the graft. Subsequently, the patient developed primary asymptomatic Epstein-Barr virus (EBV) infection, followed by EBV+ B-cell lymphoma and hepatic EBV-associated posttransplant smooth muscle tumors; therefore, the immunosuppressive treatment was greatly reduced. Since the second posttransplant year, the allografted facial skin became progressively sclerotic and presented pigmented macules on a background of hypopigmentation and teleangiectasias, resulting in a poikilodermatous aspect. Skin biopsies showed epidermal atrophy, basal cell vacuolization, and diffuse dermal sclerosis in the absence of significant dermal cell infiltration. The dermal capillaries showed thickened walls and narrowed lumina, whereas the large vessels did not show significant alterations. Neither donor-specific antibodies nor vascular Cd4 deposits were detected.A dysfunction of the graft functions occurred. It was evidenced by a decrease in mouth opening and modification of some phonemes although lip closure was still possible allowing food intake. CONCLUSIONS: This is the first report suggestive of CR in a face allotransplantation after immunosuppression minimization.
Published: 2015

44. Performances of creatinine-based glomerular filtration rate estimating equations in simultaneous pancreas-kidney transplant recipients: a single center cohort study

Author: Luciano Selistre, Olivier Thaunat, Lionel Badet, Allyriane Dantec, Vandréa De Souza, Antoine Sicard, Fanny Buron, Emmanuel Morelon, Thomas Rimmelé, Sandrine Lemoine, Laurence Dubourg, Service de Transplantation, Néphrologie et Immunologie Clinique [Hôpital Edouard Herriot, HCL], Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Universidade de Caxias do Sul, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'anesthésie-réanimation [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Lymphocytes B effecteurs et à mémoire – Effector and memory B cells, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Urologie et Chirurgie de la Transplantation, Hôpital Edouard Herriot [CHU - HCL], Laboratoire de Biologie Tissulaire et d'ingénierie Thérapeutique UMR 5305 (LBTI), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, medicine.medical_specialty, Population, Urology, Renal function, 030209 endocrinology & metabolism, Estimating equations, creatinine-based GFR estimating equations, Single Center, Kidney Function Tests, Kidney transplant, Cohort Studies, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Medicine, Humans, 030212 general & internal medicine, Cystatin C, Renal Insufficiency, Chronic, education, simultaneous pancreas-kidney transplantation, Transplantation, Creatinine, education.field_of_study, glomerular filtration rate, business.industry, Reproducibility of Results, Middle Aged, Kidney Transplantation, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, chemistry, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Regression Analysis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Pancreas Transplantation, business, Cohort study
Abstract: International audience; Estimating glomerular filtration rate (GFR) is important for clinical management and research studies in simultaneous pancreas-kidney transplantation (SPK) recipients. No study has specifically investigated the reliability of recent creatinine-based GFR estimating equations in this singular population. We assessed the performances of CKD-EPI, MDRD, Schwartz-2009, Schwartz-Lyon, Lund-Malmo and Full Age Spectrum equations for estimating GFR after SPK. 126 patients were included. GFR was measured by a reference method (mGFR) one year after SPK and estimated with the different equations from a standardized measure of serum creatinine. Relative bias, precisions, 10% and 30% accuracies (P30) were used to determine equations reliability. Ages ranged from 29 to 58. Mean mGFR was 56.3 \textpm 13.3 [23.6-92.5] ml/min/1.73 m2 . In the whole population, P30 of the CKD-EPI and MDRD equations were 42% (38.0; 46.0) and 65% (61.5; 69) respectively. As compared to the other equations, the Schwartz-Lyon equation was significantly more accurate (P30 = 86.0% [83.5-88.0], P \textless 0.01) and less biased (1.13 [1.06-1.19], P \textless 0.01). Conclusions were similar whatever the age class (\textless40 or >=40) and mGFR level (\textless60 or >=60 ml/min/1.73 m2 ). This study suggests that the CKD-EPI and MDRD equations have poor performances in SPK recipients and that the Schwartz-Lyon equation is a reliable alternative.
Published: 2018

45. Could Low-Protein Diet Modulate Nrf2 Pathway in Chronic Kidney Disease?

Author: Bengt Lindholm, Juliana Saraiva dos Anjos, Denis Fouque, Denise Mafra, Peter Stenvinkel, Ludmila F M F Cardozo, Marta Esgalhado, Service de néphrologie, Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National de la Recherche Agronomique (INRA)
Subjects: 0301 basic medicine, cisplatin-induced nephrotoxicity, NF-E2-Related Factor 2, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, nrf2/ho-1 signaling pathway, Medicine (miscellaneous), cardiovascular-disease, Inflammation, Disease, Pharmacology, medicine.disease_cause, bound uremic toxins, bardoxolone methyl, 03 medical and health sciences, 0302 clinical medicine, Low-protein diet, hemodialysis-patients, nf-kappa-b, Diet, Protein-Restricted, medicine, Humans, oxidative stress, Bardoxolone methyl, Renal Insufficiency, Chronic, Transcription factor, Nutrition and Dietetics, Nutrition & Dietetics, business.industry, Urology & Nephrology, medicine.disease, NFKB1, 3. Good health, 030104 developmental biology, Nephrology, transcription factor nrf2, medicine.symptom, business, Oxidative stress, Kidney disease, chronic-renal-failure
Abstract: International audience; Oxidative stress and inflammation are common findings in chronic kidney disease (CKD) patients, and they are directly linked to clinical outcomes such as protein energy wasting and cardiovascular disease. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is the master regulator of antioxidant genes, regulating the expression of detoxifying enzymes of phase II and antioxidant responses. Furthermore, Nrf2 can also regulate anti-inflammatory cellular responses, by inhibiting nuclear factor kappa B activity (transcription factor that promotes inflammation). Therefore, modulating Nrf2 can be a new therapeutic approach to reduce inflammation and oxidative stress in CKD. Low-protein diet (LPD) prescribed for nondialysis CKD patients presents numerous benefits already well established, including reduction of inflammation and oxidative stress. However, there is no available data regarding the relationship between LPD and Nrf2 modulation in these patients. This review aims to discuss the impact, if any, of LPD on Nrf2 expression, in nondialysis CKD patients. (C) 2017 by the National Kidney Foundation, Inc. All rights reserved.
Published: 2018

46. Is 3-Carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF) a Clinically Relevant Uremic Toxin in Haemodialysis Patients?

Author: Samuel Granjon, Anais Bouchara, Myriam Pastural, Mathilde Luce, Christophe O. Soulage, Laetitia Koppe, Maurice Laville, Denis Fouque, Walid Arkouche, Jean Christophe Szelag, Service de néphrologie, Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), INSERM, INSA-Lyon, and 'Annee Recherche' from Agence Regionale de Sante (ARS)
Subjects: 0301 basic medicine, Male, dialyse, Health, Toxicology and Mutagenesis, Metabolite, furan, [SDV]Life Sciences [q-bio], efficient removal, Toxicology, Gastroenterology, chemistry.chemical_compound, body-composition, CMPF, Uremic toxins, CKD, haemodialysis, protein energy wasting, nutrition, Wasting, uremie, 2. Zero hunger, chemistry.chemical_classification, biology, bound furancarboxylic acid, Middle Aged, Fish oil, 3. Good health, toxine, Food Science & Technology, Female, dialyzer membrane, medicine.symptom, fatty-acid, uremic toxins, medicine.medical_specialty, Nutritional Status, Article, 03 medical and health sciences, Renal Dialysis, Internal medicine, medicine, Humans, Furans, Toxicologie, albumin, Aged, Toxins, Biological, Uremia, performance liquid-chromatography, business.industry, solutes, Albumin, Fatty acid, mass-spectrometry, human serum, Transthyretin, 030104 developmental biology, chemistry, Lean body mass, biology.protein, Kidney Failure, Chronic, Propionates, business, Body mass index
Abstract: International audience; 3-Carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF) is a metabolite of furan fatty acid and a marker of fish oil intake. CMPF is described as a protein-bound uremic toxin and interacts with free oxygen radicals, which can induce cell damages. However, the clinical consequences of CMPF accumulation in haemodialysis patients remain poorly documented. The aims of this study are to investigate potential association between CMPF levels and (i) biochemical and nutritional parameters; (ii) cardiovascular events and (iii) mortality. Two hundred and fifty-two patients undergoing maintenance haemodialysis were included. Routine clinical biochemistry tests and assay for CMPF by HPLC technique were performed at the inclusion. Body composition parameters were measured using a bioimpedance spectroscopy method. The enrolled patients were prospectively monitored for cardiovascular events and mortality. CMPF level was positively correlated with nutritional parameters and lean mass and is significantly higher in patients without protein-energy wasting. However, the multivariate linear regression analysis indicated that CMPF level was not independently associated with albumin, prealbumin, creatinemia and body mass index. Elevated serum CMPF was not associated with mortality and cardiovascular morbidity. Our results indicate that CMPF is not a relevant uremic toxin in haemodialysis and in contrast could be a marker of healthy diet and omega 3 intakes.
Published: 2018

47. Mediterranean diet as the diet of choice for patients with chronic kidney disease

Author: Michel Aparicio, Daniel Teta, Pieter M. ter Wee, Anne Kolko, Philippe Chauveau, Christoph Wanner, Siren Sezer, Vincenzo Bellizzi, Denis Fouque, Juan Jesus Carrero, Xu Hong, Lina Johansson, Pablo Molina, Katrina L. Campbell, Service de néphrologie, Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL)
Subjects: health-benefits, Mediterranean diet, vegetarian diet, kidney disease, [SDV]Life Sciences [q-bio], renal outcomes, 030232 urology & nephrology, prospective cohort, Physiology, Renal function, cardiovascular-disease, 030204 cardiovascular system & hematology, Diet, Mediterranean, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, hemodialysis-patients, Medicine, Humans, Renal Insufficiency, Chronic, 2. Zero hunger, Transplantation, medicine.diagnostic_test, business.industry, Dietary management, Urology & Nephrology, medicine.disease, Micronutrient, Prognosis, Obesity, myocardial-infarction, 3. Good health, nutrition, Nephrology, Cardiovascular Diseases, all-cause mortality, glycemic index, predimed trial, business, Lipid profile, acid load, Kidney disease
Abstract: International audience; Traditional dietary management of chronic kidney disease (CKD) focuses on the quantity within the diet of energy and protein, and the restriction of single micronutrients, with little mention of dietary quality. Dietary patterns that are more plant-based, lower in meat (including processed meat), sodium and refined sugar, and have a higher content of grains and fibres are now included in multiple clinical guidelines for chronic disease prevention. The Mediterranean diet (MD) has been associated with reduced cardiovascular disease incidence in both observational and interventional studies. A wealth of evidence links MD with other beneficial effects on chronic diseases such as diabetes, obesity or cognitive health. This review examines each constituent of the classical MD and evaluates their suitability for the management of patients with CKD. We also evaluate the potential hyperkalaemia risk of increasing fruit and vegetable intake. Overall, a decrease in net endogenous acid production and increase in fibre may lead to a better control of metabolic acidosis. This, together with other putative favourable effects of MD on endothelial function, inflammation, lipid profile and blood pressure, provide mechanistic pathways to explain the observed reduced renal function decline and improved survival in CKD patients adhering to an MD.
Published: 2018

48. Full in-frame exon 3 skipping of BRCA2 confers high risk of breast and/or ovarian cancer

Author: Marine Guillaud-Bataille, Pascaline Gaidrat, Ana Vega, Dominique Stoppa-Lyonnet, Inge Søkilde, Mads Thomassen, Ana Peixoto, Florence Coulet, Claude Houdayer, Nancy Uhrhammer, Danièle Muller, Ambre Petitalot, Sandrine M. Caputo, Rita D. Brandão, Hélène Tubeuf, Laurent Castera, Virginie Moncoutier, Olga M. Sinilnikova, Aura Carreira, Alexandra Martins, Gaia Castelain, Francesca Damiola, Åsa Ehlén, Etienne Rouleau, Capucine Delnatte, Nadia Boutry-Kryza, Mélanie Léoné, Myriam Bronner, Manuel R. Teixeira, Sophie Demontety, Henriette Roed Nielsen, Amanda B. Spurdle, Uffe Birk Jensen, Sophie Krieger, Cédrick Lefol, RS: GROW - R4 - Reproductive and Perinatal Medicine, Klinische Genetica, Institut Curie [Paris], Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL), Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Stress génotoxiques et cancer, Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Paris-Sud - Paris 11 (UP11), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Genetics, Portuguese Oncology Institute, Genomic Medicine Group, University of Santiago de Compostela, Université Paris Descartes - Paris 5 (UPD5), Centre René Gauducheau, CRLCC René Gauducheau, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Génétique du cancer et des maladies neuropsychiatriques (GMFC), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Clinical Genetics, Odense University Hospital, Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Génétique, Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Groupement Hospitalier Est, Equipe 6, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Division of Genetics and Population Health, Queensland Institute of Medical Research, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), Universidade de Santiago de Compostela [Spain] (USC ), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and COLO, Mouniati
Subjects: 0301 basic medicine, PALB2, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Germline, 03 medical and health sciences, Exon, 0302 clinical medicine, Breast cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, skin and connective tissue diseases, Gene, splice donor site, Genetics, variants, Variants, Cancer, medicine.disease, BRCA2 Protein, 3. Good health, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, RNA splicing defects, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Splice donor site, Ovarian cancer, BRCA2 exon3, Research Paper
Abstract: International audience; Germline pathogenic variants in the BRCA2 gene are associated with a cumulative high risk of breast/ovarian cancer. Several BRCA2 variants result in complete loss of the exon-3 at the transcript level. The pathogenicity of these variants and the functional impact of loss of exon 3 have yet to be established. As a collaboration of the COVAR clinical trial group (France), and the ENIGMA consortium for investigating breast cancer gene variants, this study evaluated 8 BRCA2 variants resulting in complete deletion of exon 3. Clinical information for 39 families was gathered from Portugal, France, Denmark and Sweden. Multifactorial likelihood analyses were conducted using information from 293 patients, for 7 out of the 8 variants (including 6 intronic). For all variants combined the likelihood ratio in favor of causality was 4.39*1025. These results provide convincing evidence for the pathogenicity of all examined variants that lead to a total exon 3 skipping, and suggest that other variants that result in complete loss of exon 3 at the molecular level could be associated with a high risk of cancer comparable to that associated with classical pathogenic variants in BRCA1 or BRCA2 gene. In addition, our functional study shows, for the first time, that deletion of exon 3 impairs the ability of cells to survive upon Mitomycin-C treatment, supporting lack of function for the altered BRCA2 protein in these cells. Finally, this study demonstrates that any variant leading to expression of only BRCA2 delta-exon 3 will be associated with an increased risk of breast and ovarian cancer.
Published: 2018

49. The Role of Gut Microbiota and Diet on Uremic Retention Solutes Production in the Context of Chronic Kidney Disease

Author: Christophe Soulage, KOPPE Laetitia, Team1 Carmen, Carmen Lab, Team3 Carmen, Service de néphrologie, Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Service de Néphrologie [Lyon], Hospices Civils de Lyon (HCL)-Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Pillet, Lauriane, and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, insuffisance rénale, intestinal microbiota, Health, Toxicology and Mutagenesis, medicine.medical_treatment, [SDV]Life Sciences [q-bio], uremic toxins, 030232 urology & nephrology, Physiology, lcsh:Medicine, Trimethylamine N-oxide, Review, Gut flora, Toxicology, chronic kidney disease, pro, prebiotics, vegetarian diet, low protein diet, nutrient composition, chemistry.chemical_compound, 0302 clinical medicine, uremie, pro/prebiotics, biology, 3. Good health, [SDV] Life Sciences [q-bio], régime alimentaire, toxine, Food Science & Technology, chronic-renal-failure, Context (language use), 03 medical and health sciences, low-protein-diet, Low-protein diet, oligosaccharides, hemodialysis-patients, p-cresyl sulfate, medicine, Animals, Humans, Renal Insufficiency, Chronic, indoxyl sulfate, nephrectomized rats, Toxicologie, Uremia, trimethylamine-n-oxide, Diet composition, lcsh:R, biology.organism_classification, medicine.disease, Diet, Gastrointestinal Microbiome, arabinoxylan, 030104 developmental biology, Dietary protein, chemistry, Red meat intake, microflore digestive, red meat intake, plasma homocysteine, Kidney disease
Abstract: International audience; Uremic retention solutes (URS) are associated with cardiovascular complications and poor survival in chronic kidney disease. The better understanding of the origin of a certain number of these toxins enabled the development of new strategies to reduce their production. URS can be classified according to their origins (i.e., host, microbial, or exogenous). The discovery of the fundamental role that the intestinal microbiota plays in the production of many URS has reinstated nutrition at the heart of therapeutics to prevent the accumulation of URS and their deleterious effects. The intestinal microbiota is personalized and is strongly influenced by dietary habits, such as the quantity and the quality of dietary protein and fibers. Herein, this review out lines the role of intestinal microbiota on URS production and the recent discoveries on the effect of diet composition on the microbial balance in the host with a focus on the effect on URS production.
Published: 2018

50. Poor Patient and Graft Outcome After Induction Treatment by Antithymocyte Globulin in Recipients of a Kidney Graft After Nonrenal Organ Transplantation

Author: Thi Van Ha Nguyen, Jean-Paul Soulillou, Antoine Sicard, Pauline Houssel-Debry, Stéphanie Malard-Castagnet, Katy Trébern-Launay, Valérie Garrigue, Julie Laurent, Vered Padler-Karavani, Christophe Legendre, Magali Giral, Sophie Brouard, Michèle Treilhaud, Anne Cesbron, Hélène Perreault, Xi Chen, Michèle Kessler, Lionel Rostaing, Shani Leviatan Ben-Arye, Hoa Le Mai, Georges Karam, Emmanuel Morelon, Sophie Girerd, Evelyn Ang, Hai Yu, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), Department of Cell Research and Immunology, Tel Aviv University (TAU), Department of Chemistry [Univ California Davis] (Chemistry - UC Davis), University of California [Davis] (UC Davis), University of California (UC)-University of California (UC), Department of Chemistry [Winnipeg, MB, Canada], University of Manitoba [Winnipeg], Manitoba Centre for Proteomics and Systems Biology [Winnipeg, MB, Canada], Methodomics, Etablissement Français du Sang [Nantes], Département de Néphrologie et Transplantation d'organes [CHU Toulouse], Pôle Urologie - Néphrologie - Dialyse - Transplantations - Brûlés - Chirurgie plastique - Explorations fonctionnelles et physiologiques [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de Chirurgie Hépatobiliaire et Digestive [Rennes] = Hepatobiliary and Digestive Surgery [Rennes], CHU Pontchaillou [Rennes], Service Néphrologie et transplantation rénale Adultes [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Transplantation, Néphrologie et Immunologie Clinique [Hôpital Edouard Herriot, HCL], Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Lymphocytes B effecteurs et à mémoire – Effector and memory B cells, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d'urologie, Hôtel-Dieu, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Degauque, Nicolas, Tel Aviv University [Tel Aviv], Department of Chemistry Davis, University of California-University of California, Département de Néphrologie et Transplantation d'organes, Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Service de Chirurgie Hépatobiliaire et Digestive [Rennes], Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes]
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, Kidney Disease, [SDV.IMM] Life Sciences [q-bio]/Immunology, medicine.medical_treatment, Renal and urogenital, lcsh:Surgery, 030230 surgery, Organ transplantation, 03 medical and health sciences, Team2, 0302 clinical medicine, Team4, Internal medicine, medicine, CRTI, Kidney transplantation, Transplantation, Kidney, biology, business.industry, Proportional hazards model, Prevention, Immunosuppression, Organ Transplantation, lcsh:RD1-811, medicine.disease, Kidney Transplantation, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, Propensity score matching, biology.protein, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, [SDV.IMM]Life Sciences [q-bio]/Immunology, Antibody, business
Abstract: Supplemental digital content is available in the text., Background End-stage renal failure occurs in a substantial number of patients having received a nonrenal transplantation (NRT), for whom a kidney transplantation is needed. The medical strategy regarding the use of immunosuppression (IS) for a kidney graft in patients after an NRT is not well established. The prekidney grafts long-term IS advocates for a mild induction, such as using anti-IL-2R antibodies, whereas addition of new incompatibilities and anti-HLA preimmunization may suggest using stronger IS such as induction by polyclonal antithymocyte globulins (ATG). Methods We performed Cox multivariate and propensity score analysis of our validated transplant database to study the impact of the type of induction therapy on kidney graft survival of recipients of a kidney graft after NRT. Results We report here that kidney transplantation after NRT treated with an ATG induction has a poorer outcome (kidney and recipient survival) than that with an anti–IL-2R induction. After accounting for potential baseline differences with a multivariate Cox model, or by adjusting on a propensity score, we found that despite patients having received ATG cumulate more risk factors, ATG appears independently involved. As animal-derived biotherapeutics induce antiglycan antibodies and particularly anti–N-glycolylneuraminic acid (Neu5Gc) IgGs which may activate endothelial cells in patients and grafts, we also investigated the magnitude and the nature of the anti-Neu5Gc elicited by the induction and showed that induction was associated with a shift in anti-Neu5Gc IgG repertoire. Possible reasons and mechanisms of a deleterious ATG usage in these patients are discussed. Conclusions Our study suggests that ATG induction after a kidney transplantation in recipients already under maintenance IS for a NRT should be used cautiously.
Published: 2018

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Journal

Database

Publisher

160 results on '"Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL]"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources