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31 results on '"Hospices Civils de Lyon (HCL)"'

1. Proposition of a corrected measure of the Lawton instrumental activities of daily living score

Author: Dufournet, Marine, Moutet, Claire, Achi, Sarah, Delphin-Combe, Floriane, Krolak-Salmon, Pierre, Dauphinot, Virginie, Centre Mémoire de Ressources et de Recherche [Lyon] (CMRR), Hospices Civils de Lyon (HCL)-Hôpital des Charpennes [CHU - HCL], Hospices Civils de Lyon (HCL), Centre de recherche en neurosciences de Lyon (CRNL), 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), Hôpital des Charpennes [CHU - HCL], MEMORA group: Pierre Krolak-Salmon, Virginie Dauphinot, Florian Delphin-Combe, Zaza Makaroff, Denis Federico, Marie-Hélène Coste, Isabelle Rouch, Jean-Michel Dorey, Alexis Lepetit, Keren Danaila, Julien Vernaudon, Anthony Bathsavanis, Alain Sarciron, Yves Guilhermet, Sylvain Gaujard, Pierre Grosmaître, Claire Moutet, Mathieu Verdurand, Antoine Garnier-Crussard, Malbec, Odile, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), 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: Reproducibility of results, Aged, 80 and over, Male, [SDV]Life Sciences [q-bio], Dependency, [SDV] Life Sciences [q-bio], Neurocognitive disorders, Cognition, Cross-Sectional Studies, Memory, mental disorders, Activities of Daily Living, Humans, Dementia, Female, human activities, Research Article, Aged
Abstract: International audience; Background: We aimed to propose a correction of the Lawton instrumental activity of daily living (IADL) score to take into account the possibility to have never done some activities, and measured its agreement and reliability with the usual IADL score. Methods: A cross-sectional study was conducted in outpatients attending French memory clinics between 2014 and 2017. Lawton IADL, cognitive performance, diagnosis, neuropsychiatric symptoms, and sociodemographics characteristics were collected. A corrected IADL was calculated and its agreement with the usual IADL was assessed. Results: The study included of 2391 patients (79.9 years old, 61.7% female). Based on the usual IADL, 36.9% of patients had never carried out at least one of the activities. This proportion reached 68.8% for men and 17.7% for women. Women had a mean IADL higher than men: 4.72 vs 3.49, this difference decreased when considering the corrected IADL: 4.82 vs 4.26 respectively. Based on Bland-Altman method, 93.5% of observations lied within the limits agreement. The ICC between the 2 scores was 0.98. The relationships between patients' characteristics and the IADL scores were similar, regardless the usual or corrected version. Conclusions: This corrected IADL score had an excellent degree of agreement with the usual version based the ICC. This simple correction could benefit both for the clinical practice by providing a more accurate description of the real clinical state of the patients allowing to manage them more precisely, and for research involving the evaluation of the functional abilities of patients.
Published: 2021

2. Can levosimendan reduce ECMO weaning failure in cardiogenic shock? A cohort study with propensity score analysis

Author: Guilherme, E, Jacquet-Lagrèze, M, Pozzi, M, Achana, F, Armoiry, X, Fellahi, J-L, Hôpital Louis Pradel [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), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Nuffield Department of Primary Care Health Sciences, University of Oxford, University of Oxford [Oxford], Matériaux, ingénierie et science [Villeurbanne] (MATEIS), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA), Warwick Medical School, University of Warwick [Coventry], CarMeN, laboratoire, 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), University of Oxford, and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: ECMO weaning failure, Levosimendan, [SDV]Life Sciences [q-bio], Circulatory failure, lcsh:Medical emergencies. Critical care. Intensive care. First aid, lcsh:RC86-88.9, [SDV] Life Sciences [q-bio], surgical procedures, operative, VA-ECMO, Cardiogenic shock
Abstract: Background Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has been increasingly used over the last decade in patients with refractory cardiogenic shock. ECMO weaning can, however, be challenging and lead to circulatory failure and death. Recent data suggest a potential benefit of levosimendan for ECMO weaning. We sought to further investigate whether the use of levosimendan could decrease the rate of ECMO weaning failure in adult patients with refractory cardiogenic shock. Methods We performed an observational single-center cohort study. All patients undergoing VA-ECMO from January 2012 to December 2018 were eligible and divided into two groups: group levosimendan and group control (without levosimendan). The primary endpoint was VA-ECMO weaning failure defined as death during VA-ECMO treatment or within 24 h after VA-ECMO removal. Secondary outcomes were mortality at day 28 and at 6 months. The two groups were compared after propensity score matching. P Results Two hundred patients were analyzed (levosimendan group: n = 53 and control group: n = 147). No significant difference was found between groups on baseline characteristics except for ECMO duration, which was longer in the levosimendan group (10.6 ± 4.8 vs. 6.5 ± 4.7 days, p Conclusion Levosimendan did not improve the rate of successful VA-ECMO weaning in patients with refractory cardiogenic shock. Trial registration ClinicalTrials.gov, NCT04323709.
Published: 2020

3. Study protocol of the HYPER-LIV01 trial: a multicenter phase II, prospective and randomized study comparing simultaneous portal and hepatic vein embolization to portal vein embolization for hypertrophy of the future liver remnant before major hepatectomy for colo-rectal liver metastases

Author: François Quenet, Christian Sengel, Lauranne Piron, Anthony Dohan, Patrick Chevallier, Emilie Lermite, Chloé Guillot, Boris Guiu, Laurent Vervueren, Agnès Rode, Antoine Bouvier, Jean-Baptiste Pinaquy, Christophe Laurent, Emmanuel Deshayes, Bruno Lapuyade, Salvy-Córdoba, Nathalie, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut du Cancer de Montpellier (ICM), Département radiologie diagnostique et interventionnelle Saint Eloi [CHRU Montpellier], Pôle Digestif [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Bordeaux [Bordeaux], CHU d'Angers [Département Urgences], PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Universitaire de Nice (CHU Nice), Service de Radiologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Radiologie [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), and Centre Hospitalier Universitaire [Grenoble] (CHU)
Subjects: Male, Cancer Research, [SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery, medicine.medical_treatment, MESH: Hepatomegaly, Phases of clinical research, 030218 nuclear medicine & medical imaging, Muscle hypertrophy, law.invention, Study Protocol, Liver metastases, 0302 clinical medicine, Portal vein embolization, Postoperative Complications, Randomized controlled trial, law, Surgical oncology, MESH: Liver Neoplasms, MESH: Postoperative Complications, Medicine, Multicenter Studies as Topic, Embolization, Prospective Studies, MESH: Treatment Outcome, Randomized Controlled Trials as Topic, MESH: Middle Aged, Portal Vein, Liver Neoplasms, MESH: Follow-Up Studies, MESH: Hepatectomy, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Embolization, Therapeutic, medicine.anatomical_structure, Treatment Outcome, Oncology, Colo-rectal cancer, Liver, 030220 oncology & carcinogenesis, MESH: Liver Regeneration, Female, Colorectal Neoplasms, MESH: Clinical Trials, Phase II as Topic, Hepatomegaly, MESH: Preoperative Care, Venous deprivation, Adult, medicine.medical_specialty, Major hepatectomy, Urology, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, lcsh:RC254-282, 03 medical and health sciences, Clinical Trials, Phase II as Topic, [SDV.CAN] Life Sciences [q-bio]/Cancer, Preoperative Care, Genetics, Hepatectomy, Humans, Vein, MESH: Liver Failure, MESH: Humans, business.industry, MESH: Adult, MESH: Portal Vein, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH: Prospective Studies, MESH: Male, Liver Regeneration, MESH: Embolization, Therapeutic, MESH: Randomized Controlled Trials as Topic, Tumor progression, MESH: Multicenter Studies as Topic, Liver function, business, MESH: Female, MESH: Colorectal Neoplasms, Liver Failure, MESH: Liver, Follow-Up Studies
Abstract: Background In patients undergoing major liver resection, portal vein embolization (PVE) has been widely used to induce hypertrophy of the non-embolized liver in order to prevent post-hepatectomy liver failure. PVE is a safe and effective procedure, but does not always lead to sufficient hypertrophy of the future liver remnant (FLR). Hepatic vein(s) embolization has been proposed to improve FLR regeneration when insufficient after PVE. The sequential right hepatic vein embolization (HVE) after right PVE demonstrated an incremental effect on the FLR but it implies two different procedures with no time gain as compared to PVE alone. We have developed the so-called liver venous deprivation (LVD), a combination of PVE and HVE during the same intervention, to optimize the phase of liver preparation before surgery. The main objective of this randomized phase II trial is to compare the percentage of change in FLR volume at 3 weeks after LVD or PVE. Methods Patients eligible to this multicenter prospective randomized phase II study are subjects aged from 18 years old suffering from colo-rectal liver metastases considered as resectable and with non-cirrhotic liver parenchyma. The primary objective is the percentage of change in FLR volume at 3 weeks after LVD or PVE using MRI or CT-Scan. Secondary objectives are assessment of tolerance, post-operative morbidity and mortality, post-hepatectomy liver failure, rate of non-respectability due to insufficient FLR or tumor progression, per-operative difficulties, blood loss, R0 resection rate, post-operative liver volume and overall survival. Objectives of translational research studies are evaluation of pre- and post-operative liver function and determination of biomarkers predictive of liver hypertrophy. Sixty-four patients will be included (randomization ratio 1:1) to detect a difference of 12% at 21 days in FLR volumes between PVE and LVD. Discussion Adding HVE to PVE during the same procedure is an innovative and promising approach that may lead to a rapid and major increase in volume and function of the FLR, thereby increasing the rate of resectable patients and limiting the risk of patient’s drop-out. Trial registration This study was registered on clinicaltrials.gov on 15th February 2019 (NCT03841305).
Published: 2020

4. Anatomic risk factor for meniscal lesion in association with ACL rupture

Author: Sébastien Lustig, Elvire Servien, Robert A. Magnussen, Philippe Neyret, Romain Gaillard, Cécile Batailler, Service de Chirurgie Orthopédique [Centre Albert Trillat], Centre Albert Trillat [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Ohio State University [Columbus] (OSU), Laboratoire de Biomécanique et Mécanique des Chocs (LBMC UMR T9406 ), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Gustave Eiffel, Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)
Subjects: CT scan, Adult, Male, medicine.medical_specialty, lcsh:Diseases of the musculoskeletal system, Adolescent, Menisci, Tibial, ANATOMIE, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Sex Factors, lcsh:Orthopedic surgery, Risk Factors, medicine, Humans, Orthopedics and Sports Medicine, Femur, Single-Blind Method, Tibia, [PHYS.MECA.BIOM]Physics [physics]/Mechanics [physics]/Biomechanics [physics.med-ph], Risk factor, Meniscal tear, Retrospective Studies, 030203 arthritis & rheumatology, 030222 orthopedics, Anterior Cruciate Ligament Reconstruction, business.industry, ACL, Anterior Cruciate Ligament Injuries, Middle Aged, musculoskeletal system, Sagittal plane, Surgery, lcsh:RD701-811, Acl rupture, medicine.anatomical_structure, Concomitant, Orthopedic surgery, Female, lcsh:RC925-935, Anatomy, business, Meniscal lesions, Research Article
Abstract: Background To assess anatomic risk factors for meniscal lesions in association with acute ACL rupture. The primary hypothesis was that tibiofemoral anatomic measures will be different in those with and without concomitant meniscus tears. Methods A retrospective review of patients who underwent acute ACL reconstruction in the department was performed. All patients underwent a postoperative CT scan. The concavity and/or convexity on the femur and the tibia were measured by two blinded observers on the sagittal plane with different ratios, and these measures were compared in patients with and without meniscus tears in each compartment. Intra- and inter-rater reliabilities were assessed. Results Four hundred twelve patients (268 males and 144 females) were included from October 2012 to February 2015. One hundred sixty-seven patients had a medial meniscal tear (119 males/48 females), and 100 had a lateral meniscal tear (80 males/20 females). The mean time from injury to surgery was 3 months. The average ICC for all measurements was 0.87 (range 0.82–0.98) indicating good reliability. The medial femoral condyle was noted to be significantly longer than the medial tibial plateau in the sagittal plane in patients with a medial meniscal tear (p = 0.04), and the lateral femoral condyle was noted to be significantly longer than the lateral tibial plateau in the sagittal plane in patients with a lateral meniscal tear (p
Published: 2019

5. Cross sectional study on prevalence of sickle cell alleles S and C among patients with mild malaria in Ivory Coast

Author: Serge-Brice Assi, Baba Coulibaly, Stephane Koui Tossea, David N’golo Coulibaly, Philippe Joly, Eric Gbessi Adji, Berenger Ako Ako, Ronan Jambou, André Offianan Touré, Institut Pasteur de Côte d'Ivoire, Réseau International des Instituts Pasteur (RIIP), Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM), Unité de Pathologie Moléculaire du Globule Rouge, Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Institut Pierre Richet (IPR), Programme National de Lutte Contre le Paludisme [Côte d'Ivoire], Ministère de la Santé [Côte d'Ivoire], Département Parasites et Insectes vecteurs - Department of Parasites and Insect Vectors, Institut Pasteur [Paris], This study was supported by a grant from the International Rotary foundation and the District of Paris Rotary., Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), and Institut Pasteur [Paris] (IP)
Subjects: Male, Cross-sectional study, [SDV]Life Sciences [q-bio], Hemoglobin, Sickle, lcsh:Medicine, Comorbidity, 0302 clinical medicine, Pregnancy, Genotype, Prevalence, 030212 general & internal medicine, Child, lcsh:QH301-705.5, education.field_of_study, Geography, Hemoglobin C, General Medicine, Sickle cell anemia, 3. Good health, Research Note, Child, Preschool, Female, Ivory Coast, Adult, medicine.medical_specialty, Adolescent, 030231 tropical medicine, Population, Anemia, Sickle Cell, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Young Adult, Internal medicine, parasitic diseases, medicine, Humans, lcsh:Science (General), education, Alleles, Retrospective Studies, business.industry, lcsh:R, Infant, Newborn, Infant, Retrospective cohort study, medicine.disease, Abnormal hemoglobin, Malaria, Cote d'Ivoire, Cross-Sectional Studies, lcsh:Biology (General), Pregnancy Complications, Parasitic, FRET, Hemoglobin, business, lcsh:Q1-390
Abstract: Objectives Sickle cell anemia is due to a mutations on the betaglobin gene, inducing abnormal hemoglobin. In West Africa the main mutations lead to S or C types of hemoglobin. Patients with homozygote mutations seem protected against severe malaria, but not against mild disease. The prevalence of abnormal hemoglobin among patients attending dispensaries for mild malaria is thus unknown. A retrospective study was conducted to update data on the prevalence of S and C hemoglobin among patients attending dispensaries with mild malaria. Enrolment of patients was conducted during in vivo malaria treatment efficacy survey following the 42 days WHO protocol. A group of non-infected pregnant women and a group of patients with fever different from malaria, were also recruited in the same dispensaries. Results 794 blood samples were included. S and C genotypes were found in all the regions of Ivory Coast with the highest prevalence in the Northern region (S and C genotypes, 27%). In non-infected patients, prevalence of mutations was higher than in malaria patients. Conclusion A high proportion of patients with mild malaria carried genetic hemoglobin disorder. This population of high risk must be better investigated to control treatment efficacy and to manage complications. Electronic supplementary material The online version of this article (10.1186/s13104-018-3296-7) contains supplementary material, which is available to authorized users.
Published: 2018

6. High-flow nasal oxygen vs. standard oxygen therapy in immunocompromised patients with acute respiratory failure: study protocol for a randomized controlled trial

Author: Alexandre Demoule, Naïke Bigé, Jean Reignier, Jean-Herlé Raphalen, François Barbier, Lila Bouadma, Frédéric Pène, Antoine Rabbat, Michael Darmon, Christophe Girault, Nicolas Terzi, Pierre Perez, Virginie Lemiale, Alexandre Lautrette, Fabrice Bruneel, Martine Nyunga, Loay Kontar, Julien Mayaux, Elie Azoulay, Florent Wallet, Laurent Argaud, Samir Jaber, Laurent Papazian, Djamel Mokart, Guillaume Louis, Sylvie Chevret, Christine Lebert, Saad Nseir, Kada Klouche, Johanna Oziel, Achille Kouatchet, Vincent Peigne, Anabelle Stoclin, Jean-Michel Constantin, Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hospices Civils de Lyon (HCL), Service de réanimation [CH Versailles], Centre Hospitalier de Versailles André Mignot (CHV), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Horticulture et Semences (IRHS), Université d'Angers (UA)-Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Service d'anesthésie et réanimation chirurgicale [Nantes], Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), CHU Clermont-Ferrand, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service de réanimation médicale, 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), CHU Rouen, Normandie Université (NU), Medical-Surgical Intensive Care Unit, Avicenne University Hospital, APHP, 125 rue de Stalingrad, Bobigny 93009, France, Avicenne University Hospital, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Bichat - Claude Bernard, Service de Réanimation Polyvalente, CH Départemental Vendée, Unité de soins intensifs [Clermont Ferrand], CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], Service des Soins Intensifs [CHU Saint-Antoine], 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), Hôpital Sainte-Marguerite, CHU Marseille, Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service des Urgences et de Réanimation Médicale (Urg - SAINT ETIENNE), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Biostatistique et épidemiologie clinique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), réanimation chirurgicale, CH Versailles, Ministère de la santé, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), AGROCAMPUS OUEST-Institut National de la Recherche Agronomique (INRA)-Université d'Angers (UA), CHU Pitié-Salpêtrière [APHP], Department of Anesthesia and Critical Care Medicine, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Clermont-Ferrand-Hôpital Gabriel Montpied, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), and MORNET, Dominique
Subjects: Time Factors, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Medicine (miscellaneous), medicine.disease_cause, Acute respiratory failure, law.invention, Study Protocol, 0302 clinical medicine, Randomized controlled trial, Immunocompromised Hematology, law, Oxygen therapy, Medicine, Multicenter Studies as Topic, Pharmacology (medical), Prospective Studies, education.field_of_study, lcsh:R5-920, Respiratory distress, Mortality rate, Intensive care unit, 3. Good health, [SDV] Life Sciences [q-bio], Intensive Care Units, Treatment Outcome, Anesthesia, Acute Disease, France, lcsh:Medicine (General), Respiratory Insufficiency, Nasal cannula, Population, Equivalence Trials as Topic, 03 medical and health sciences, Immunocompromised Host, High-flow oxygen, Intensive care, Cannula, Humans, Mortality, education, business.industry, Oxygen Inhalation Therapy, 030208 emergency & critical care medicine, Oxygen, 030228 respiratory system, business, Intubation, Immunosuppression
Abstract: Acute respiratory failure (ARF) is the leading reason for intensive care unit (ICU) admission in immunocompromised patients. High-flow nasal oxygen (HFNO) therapy is an alternative to standard oxygen. By providing warmed and humidified gas, HFNO allows the delivery of higher flow rates via nasal cannula devices, with FiO2 values of nearly 100%. Benefits include alleviation of dyspnea and discomfort, decreased respiratory distress and decreased mortality in unselected patients with acute hypoxemic respiratory failure. However, in preliminary reports, HFNO benefits are controversial in immunocompromised patients in whom it has never been properly evaluated., ClinicalTrials.gov, ID: NCT02739451 . Registered on 15 April 2016.
Published: 2018

7. Chronic Lyme borreliosis associated with minimal change glomerular disease: a case report

Author: Maud Rabeyrin, Fitsum Guebre-Egziabher, J. Kanitakis, Sandrine Lemoine, Nans Florens, Florent Valour, Laurent Juillard, 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), Department of Infectious Diseases and Tropical Medicine, Hospices Civils de Lyon (HCL), Departement det Dermatologie, Departement de Pathologie, Centre médical universitaire de Genève (CMU), 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), and Université de Lyon-Institut National de la Recherche Agronomique (INRA)
Subjects: Nephrology, Pathology, lésion cutanée, Nephrotic Syndrome, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Case Report, examen clinique, Kidney, 0302 clinical medicine, Lyme disease, Minimal change disease, 030212 general & internal medicine, Borreliosis, pathogénèse, Skin, Lyme Disease, medicine.diagnostic_test, diagnostic techniques, pathogenesis, Ceftriaxone, 3. Good health, LYME, Anti-Bacterial Agents, Renal pathology, Female, Renal biopsy, Chronic atrophic acrodematitis, medicine.medical_specialty, lyme, borreliosis, minimal change disease, chronic atrophic acrodematitis, Prednisolone, 03 medical and health sciences, Internal medicine, corticostéroïde, medicine, Humans, Glucocorticoids, Aged, business.industry, Nephrosis, Lipoid, Acrodermatitis, maladie de lyme, medicine.disease, Dermatology, Skin biopsy, Chronic Disease, Lyme, business, Nephrotic syndrome
Abstract: Background: There are only few cases of renal pathology induced by Lyme borreliosis in the literature, as this damage is rare and uncommon in humans. This patient is the first case of minimal change glomerular disease associated with chronic Lyme borreliosis. Case presentation: A 65-year-old Caucasian woman was admitted for an acute edematous syndrome related to a nephrotic syndrome. Clinical examination revealed violaceous skin lesions of the right calf and the gluteal region that occurred 2 years ago. Serological tests were positive for Lyme borreliosis and skin biopsy revealed lesions of chronic atrophic acrodermatitis. Renal biopsy showed minimal change glomerular disease. The skin lesions and the nephrotic syndrome resolved with a sequential treatment with first ceftriaxone and then corticosteroids. Conclusion: We report here the first case of minimal change disease associated with Lyme borreliosis. The pathogenesis of minimal change disease in the setting of Lyme disease is discussed but the association of Lyme and minimal change disease may imply a synergistic effect of phenotypic and bacterial factors. Regression of proteinuria after a sequential treatment with ceftriaxone and corticosteroids seems to strengthen this conceivable association.
Published: 2017

8. Intradermal injection of human adipose-derived stem cells accelerates skin wound healing in nude mice

Author: Ali Mojallal, Ondine Rouyer, Charlotte Lequeux, Audrey Josset-Lamaugarny, F. Boucher, Orianne Ardisson, Dominique Sigaudo-Roussel, Jonathan Rodriguez, Héléna Rutschi, Odile Damour, 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), Banque Tissus and Cellules, Laboratoire Substituts Cutanés, Hospices Civils de Lyon (HCL), Service Chirurgie Plast Esthétique et Reconstructrice, Banque Tissus et Cellules, Laboratoire Substituts Cutanés, 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), Centre National de la Recherche Scientifique (CNRS), Institut de biologie et chimie des protéines [Lyon] (IBCP), Laboratoire Central d'Anatomie Pathologique, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Revitacare laboratory, IHU OPeRa, 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), ProdInra, Archive Ouverte, 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: Adipose-derived stem cells, Male, Pathology, Time Factors, Skin blood perfusion, Medicine (miscellaneous), Adipose tissue, tissu adipeux, Human skin, Vehicle, Mice, 0302 clinical medicine, Medicine, Intradermal injection, Stem cell transplantation for articular cartilage repair, adipose-derived stem cell, Skin, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, integumentary system, Bone Marrow Stem Cell, 3. Good health, Adipose Tissue, 030220 oncology & carcinogenesis, Molecular Medicine, Stem cell, cutaneous wound healing, skin blood perfusion, vehicle, medicine.medical_specialty, Injections, Intradermal, Médecine humaine et pathologie, Mice, Nude, Context (language use), voie intradermique, Biochemistry, Genetics and Molecular Biology (miscellaneous), 03 medical and health sciences, Cicatrix, cellule souche, Animals, Humans, skin drug administration, 030304 developmental biology, Wound Healing, business.industry, Research, Cell Biology, stem cell, Cutaneous wound healing, Human health and pathology, business, Wound healing, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Stem Cell Transplantation
Abstract: Background The use of stem cells from adipose tissue or adipose-derived stem cells (ASCs) in regenerative medicine could be an interesting alternative to bone marrow stem cells because they are easily accessible and available in large quantities. The aim of this study was to evaluate the potential effect of ASCs on the healing of 12 mm diameter-excisional wounds (around 110 mm2) in nude mice. Methods Thirty nude mice underwent surgery to create one 12-mm excisional wound per mouse (spontaneous healing, n = 6; Cytocare® 532, n = 12; ASCs, n = 12). The Galiano wound model was chosen to avoid shrinkage and thus slow the spontaneous healing (SH) of mouse skin, making it closer to the physiology of human skin healing. Transparent dressings were used to enable daily healing time measurements to be taken. Immunohistochemistry, histological and blood perfusion analysis were carried out on the healed skin. Results The in vivo results showed the effectiveness of using ASCs on reducing the time needed for complete healing to 21.2 days for SH, 17.4 days for vehicle alone (Cytocare® 532) and 14.6 days with the addition of ASCs (p Conclusions The tolerance and efficacy of cryopreserved ASCs to accelerate the complete closure of the wound by increasing the maturation of the skin and its blood perfusion, shows their therapeutic benefit in the wound healing context.
Published: 2015

9. Targeted screening for third-generation cephalosporin-resistant Enterobacteriaceae carriage among patients admitted to intensive care units: a quasi-experimental study

Author: Olivier Dauwalder, Romain Hernu, Bernard Allaouchiche, Philippe Vanhems, Laurent Argaud, Thomas Bénet, Cédric Dananché, François Vandenesch, 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), 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), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National de la Recherche Agronomique (INRA)
Subjects: Pediatrics, medicine.medical_specialty, infection-control, [SDV]Life Sciences [q-bio], Rectum, Critical Care and Intensive Care Medicine, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, Enterobacteriaceae, Intensive care, General & Internal Medicine, medicine, Infection control, Humans, Mass Screening, 030212 general & internal medicine, Poisson regression, spectrum beta-lactamase, risk-factors, interventions, Mass screening, 0303 health sciences, Cross Infection, Infection Control, Cephalosporin Resistance, 030306 microbiology, business.industry, staphylococcus-aureus, Incidence (epidemiology), Research, Incidence, transmission, colonization, gram-negative bacteria, Confidence interval, 3. Good health, Anti-Bacterial Agents, Cephalosporins, Intensive Care Units, Carriage, medicine.anatomical_structure, admission, Carrier State, symbols, escherichia-coli, epidemiology, business
Abstract: Introduction Identification of third-generation, cephalosporin-resistant Enterobacteriaceae (3GC-RE) carriers by rectal screening at admission seems to be an important step in the prevention of transmission and outbreaks; however, little is known about its effectiveness. The aim of this study was to evaluate the impact of ‘targeted screening’ at patient admission to intensive care units (ICUs) on the incidence of 3GC-RE hospital-acquired infections (HAIs) and compare it to ‘universal screening’. Methods We undertook a quasi-experimental study of two ICUs (unit A: intervention group; unit B: control group) at a university-affiliated hospital between 1 January 2008 and 31 December 2011. In unit A, patients were screened universally for 3GC-RE at admission during period 1 (1 January 2008 through 30 September 2010). During period 2 (2011 calendar year), the intervention was implemented in unit A; patients transferred from another unit or hospital were screened selectively. In unit B, all patients were screened throughout periods 1 and 2. 3GC-RE-related HAI incidence rates were expressed per 1,000 patient-days. Incidence rate ratios (IRRs) were examined by multivariate Poisson regression modelling. Results In unit A, 3GC-RE-related HAI incidence rates decreased from 5.4 (95% confidence interval (CI), 4.1 to 7.0) during period 1 to 1.3 (95% CI, 0.5 to 2.9) during period 2 (P P = 0.5). In unit A, the adjusted incidence of 3GC-RE-related HAIs decreased in period 2 compared with period 1 (adjusted IRR, 0.3; 95% CI, 0.1 to 0.9; P = 0.03) independently of temporal trend, trauma and age. No changes were seen in unit B (P = 0.4). The total number of rectal swabs taken showed an 85% decrease in unit A between period 1 and 2 (P Conclusions Targeted screening of 3GC-RE carriers at ICU admission was not associated with an increase in 3GC-RE-related HAI incidence compared with universal screening. Total number of rectal swabs decreased significantly. These findings suggest that targeted screening may be worth assessing as an alternative to universal screening.
Published: 2015

10. In vivo free-breathing DTI & IVIM of the whole human heart using a real-time slice-followed SE-EPI navigator-based sequence: a reproducibility study in healthy volunteers

Author: Pierre Croisille, Thorsten Feiweier, Olivier Beuf, Bénédicte M. A. Delattre, Kevin Moulin, Benjamin Robert, Magalie Viallon, Hongjiang Wei, RMN et optique : De la mesure au biomarqueur, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), 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)-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 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)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Siemens Healthcare [France], Siemens AG [Munich], Service de radiologie [Saint-Etienne], CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM), and Siemens AG Healthcare Sector, Erlangen
Subjects: [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, 02 engineering and technology, computer.software_genre, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, In vivo, Fractional anisotropy, 0202 electrical engineering, electronic engineering, information engineering, Medicine, Radiology, Nuclear Medicine and imaging, Intravoxel incoherent motion, Medicine(all), Reproducibility, Sequence, Radiological and Ultrasound Technology, business.industry, Duty cycle, Maximum intensity projection, Poster Presentation, 020201 artificial intelligence & image processing, Data mining, Cardiology and Cardiovascular Medicine, business, computer, Free breathing, Biomedical engineering
Abstract: In this study, we proposed an efficient free-breathing strategy for rapid and improved cardiac diffusion-weighted imaging (DWI) acquisition using a single-shot spin-echo echo planar imaging (SE-EPI) sequence. Methods: A real-time slice-following technique during free-breathing was combined with a sliding acquisition-window strategy prior Principal Component Analysis temporal Maximum Intensity Projection (PCAtMIP) postprocessing of in-plane co-registered diffusion-weighted images. This methodology was applied to 10 volunteers to quantify the performance of the motion correction technique and the reproducibility of diffusion parameters. Results: The slice-following technique offers a powerful head–foot respiratory motion management solution for SE-EPI cDWI with the advantage of a 100% duty cycle scanning efficiency. The level of co-registration was further improved using nonrigid motion corrections and was evaluated with a co-registration index. Vascular fraction f and the diffusion coefficients D and D* were determined to be 0.122 ± 0.013, 1.41 ± 0.09 × 10−3 mm2/s and 43.6 ± 9.2 × 10−3 mm2/s, respectively. From the multidirectional dataset, the measured mean diffusivity was 1.72 ± 0.09 × 10−3 mm2/s and the fractional anisotropy was 0.36 ± 0.02. Conclusion: The slice-following DWI SE-EPI sequence is a promising solution for clinical implementation, offering a robust improved workflow for further evaluation of DWI in cardiology. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc.
Published: 2015

11. The prediction of hospital length of stay using unstructured data

Author: Jan Chrusciel, François Girardon, Lucien Roquette, David Laplanche, Antoine Duclos, Stéphane Sanchez, CH de Troyes, CODOC SAS [Paris] (CS), Research on Healthcare Performance (RESHAPE - Inserm U1290 - UCBL1), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL), and Malbec, Odile
Subjects: Emergency department, Health Policy, [SDV]Life Sciences [q-bio], Research, Computer applications to medicine. Medical informatics, R858-859.7, Health Informatics, Hospitals, Computer Science Applications, [SDV] Life Sciences [q-bio], Hospitalization, Length of stay, Health services research, Humans, Emergency Service, Hospital, Data mining, Retrospective Studies
Abstract: Objective This study aimed to assess the performance improvement for machine learning-based hospital length of stay (LOS) predictions when clinical signs written in text are accounted for and compared to the traditional approach of solely considering structured information such as age, gender and major ICD diagnosis. Methods This study was an observational retrospective cohort study and analyzed patient stays admitted between 1 January to 24 September 2019. For each stay, a patient was admitted through the Emergency Department (ED) and stayed for more than two days in the subsequent service. LOS was predicted using two random forest models. The first included unstructured text extracted from electronic health records (EHRs). A word-embedding algorithm based on UMLS terminology with exact matching restricted to patient-centric affirmation sentences was used to assess the EHR data. The second model was primarily based on structured data in the form of diagnoses coded from the International Classification of Disease 10th Edition (ICD-10) and triage codes (CCMU/GEMSA classifications). Variables common to both models were: age, gender, zip/postal code, LOS in the ED, recent visit flag, assigned patient ward after the ED stay and short-term ED activity. Models were trained on 80% of data and performance was evaluated by accuracy on the remaining 20% test data. Results The model using unstructured data had a 75.0% accuracy compared to 74.1% for the model containing structured data. The two models produced a similar prediction in 86.6% of cases. In a secondary analysis restricted to intensive care patients, the accuracy of both models was also similar (76.3% vs 75.0%). Conclusions LOS prediction using unstructured data had similar accuracy to using structured data and can be considered of use to accurately model LOS.
Published: 2021

12. Lower ribavirin biodisponibility in patients with HIV-HCV coinfection in comparison with HCV monoinfected patients

Author: Marie-Claude Gagnieu, Patrick Miailhes, Jean-Michel Livrozet, Fabien Zoulim, François Parant, François Bailly, Marianne Maynard, Pierre Chiarello, Giorgiana Hatu, Pierre Pradat, Emmanuel Pourcelot, Service d'hépatologie, Hospices Civils de Lyon (HCL)-Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Université de Médicine et Pharmacie 'Iuliu Hatieganu', 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), Pharmacologie, Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'immunologie, BMC, Ed., 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)
Subjects: Male, HIV Infections, medicine.disease_cause, 030226 pharmacology & pharmacy, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, Pegylated interferon, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 0303 health sciences, education.field_of_study, Human immunodeficiency virus, Coinfection, Area under the curve, virus diseases, Hepatitis C, Middle Aged, 3. Good health, Infectious Diseases, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, medicine.drug, Research Article, Adult, medicine.medical_specialty, Combination therapy, Hepatitis C virus, Population, Biological Availability, Antiviral Agents, Ribavirin exposure, 03 medical and health sciences, Young Adult, Internal medicine, Ribavirin, medicine, Humans, education, Aged, 030306 microbiology, business.industry, Hepatitis C, Chronic, medicine.disease, Treatment, chemistry, Immunology, business
Abstract: International audience; BACKGROUND: In HIV infected patients, the impact of ribavirin (RBV) pharmacology on sustained virologic response (SVR) to hepatitis C virus (HCV) treatment has not been fully investigated. The objective of this study was to compare the early RBV plasma exposure between a population of HIV-HCV coinfected patients and an HCV monoinfected group. METHODS: Early RBV plasma exposure (expressed as Area Under the Curve (AUC) from 0 to 4 h) after a 600 mg first dose of RBV was measured in a population of HIV-HCV coinfected patients in comparison with an HCV monoinfected group. Peripheral blood samples were collected before the 600 mg RBV first dose (T0) to ensure no detectable baseline plasma RBV, and then 30 mn, 1, 2 and 4 hours after RBV intake (T0.5, T1, T2 and T4). RESULTS: Eighty-six patients with chronic hepatitis C entered the study among whom 23 (27%) were HIV-HCV coinfected. Coinfected patients had a significantly lower RBV-AUC(0-4h) (median: 1469 μg*h/L [range 936-3677]) compared with monoinfected patients (2030 μg*h/L [851-7700]; p = 0.018). This RBV under exposure in coinfected patients persisted after normalization of AUC to RBV dose per kilogram of body weight (182 μg*h/L [110-425] versus 271 μg*h/L [82-1091], p = 0.001). CONCLUSIONS: These results suggest that lower early bioavailability of RBV could be one of the reasons for lower SVR in HIV-HCV coinfected patients treated with pegylated interferon/RBV combination therapy. RBV plasma underexposure seems to be associated with the immunological status of the patients with lower AUC(0-4h) values observed in the more immunosuppressed coinfected patients.
Published: 2014

13. Potential of pre-contrast T1 mapping as a marker of interstitial fibrosis in severe aortic stenosis

Author: Rick Wage, Raad H. Mohiaddin, Sanjay K Prasad, Dudley J. Pennell, Mario Petrou, David N. Firmin, Pedro F. Ferreira, Benjamin Hewins, Carl Shakespeare, Taigang He, Andrew Jabbour, Oluwatosin Sotubo, Saman Zaman, Ankur Gulati, Tevfik F Ismail, Yanqiu Feng, Callum Ettles, Pierre Croisille, Sameer Zaman, John Pepper, National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, RMN et optique : De la mesure au biomarqueur, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-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 Claude Bernard Lyon 1 (UCBL), Institut National des Sciences Appliquées (INSA)-Université de Lyon-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), Cardiothoracic Surgery, 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 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)-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 BMC, Ed.
Subjects: Pathology, medicine.medical_specialty, lcsh:Diseases of the circulatory (Cardiovascular) system, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Interstitial fibrosis, Septal wall, Pre contrast, Left atrial dilatation, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, Radiology, Nuclear Medicine and imaging, ComputingMilieux_MISCELLANEOUS, Angiology, Medicine(all), Radiological and Ultrasound Technology, Strain (chemistry), business.industry, medicine.disease, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Stenosis, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, lcsh:RC666-701, Cardiology, Oral Presentation, Cardiology and Cardiovascular Medicine, business
Abstract: circumferential max strain (r=0.43, p=0.03), angle δ strain (r=0.78, p=0.001), and motion magnitude peak strain (r=0.87, p
Published: 2012

14. Regulation of chemokine and chemokine receptor expression by PPARG in adipocytes and macrophages

Author: Ai Chen, David Patsouris, WuQiang Fan, Pingping Li, MT A Nguyen, Da Young Oh, Wendell J. Lu, Dept. of Medicine, University of California, 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), BMC, Ed., University of California (UC), 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), 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), and Université de Lyon-Institut National de la Recherche Agronomique (INRA)
Subjects: Male, Chemokine, Anatomy and Physiology, endocrine system diseases, Gene Expression, lcsh:Medicine, Adipose tissue, Fatty Acids, Nonesterified, Mice, chemistry.chemical_compound, Chemokine receptor, Endocrinology, 0302 clinical medicine, Immune Physiology, Adipocyte, Immunologie, Adipocytes, Medicine, Thiazolidinedione, lcsh:Science, ComputingMilieux_MISCELLANEOUS, Medicine(all), 0303 health sciences, Arachidonic Acid, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Multidisciplinary, biology, General Medicine, Endoplasmic Reticulum Stress, Adipose Tissue, 030220 oncology & carcinogenesis, Cytokines, [SDV.IMM]Life Sciences [q-bio]/Immunology, Receptors, Chemokine, Chemokines, medicine.symptom, Rosiglitazone, Signal Transduction, Research Article, medicine.drug, Drugs and Devices, medicine.medical_specialty, Peroxisome proliferator-activated receptor gamma, Drug Research and Development, [SDV.IMM] Life Sciences [q-bio]/Immunology, medicine.drug_class, Immunology, Down-Regulation, Médecine humaine et pathologie, Inflammation, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Insulin resistance, Internal medicine, Animals, Hypoglycemic Agents, Obesity, Biology, Nutrition, 030304 developmental biology, Diabetic Endocrinology, Chemotactic Factors, Biochemistry, Genetics and Molecular Biology(all), business.industry, Macrophages, lcsh:R, Immunity, nutritional and metabolic diseases, medicine.disease, Mice, Inbred C57BL, PPAR gamma, Toll-Like Receptor 4, chemistry, Immune System, Poster Presentation, biology.protein, Cancer research, Thiazolidinediones, Clinical Immunology, lcsh:Q, Human health and pathology, ComputingMethodologies_GENERAL, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background PPARγ plays a key role in adipocyte biology, and Rosiglitazone (Rosi), a thiazolidinedione (TZD)/PPARγ agonist, is a potent insulin-sensitizing agent. Recent evidences demonstrate that adipose tissue inflammation links obesity with insulin resistance and that the insulin-sensitizing effects of TZDs result, in part, from their anti-inflammatory properties. However the underlying mechanisms are unclear. Methodology and Principal Findings In this study, we establish a link between free fatty acids (FFAs) and PPARγ in the context of obesity-associated inflammation. We show that treatment of adipocytes with FFAs, in particular Arachidonic Acid (ARA), downregulates PPARγ protein and mRNA levels. Furthermore, we demonstrate that the downregulation of PPARγ by ARA requires the activation the of Endoplamsic Reticulum (ER) stress by the TLR4 pathway. Knockdown of adipocyte PPARγ resulted in upregulation of MCP1 gene expression and secretion, leading to enhanced macrophage chemotaxis. Rosi inhibited these effects. In a high fat feeding mouse model, we show that Rosi treatment decreases recruitment of proinflammatory macrophages to epididymal fat. This correlates with decreased chemokine and decreased chemokine receptor expression in adipocytes and macrophages, respectively. Conclusions and Significance In summary, we describe a novel link between FAs, the TLR4/ER stress pathway and PPARγ, and adipocyte-driven recruitment of macrophages. We thus both describe an additional potential mechanism for the anti-inflammatory and insulin-sensitizing actions of TZDs and an additional detrimental property associated with the activation of the TLR4 pathway by FA.
Published: 2011

15. Severe metabolic or mixed acidemia on intensive care unit admission: incidence, prognosis and administration of buffer therapy. a prospective, multiple-center study

Author: Laurent Muller, Laurent Papazian, Thomas Rimmelé, Boris Jung, Jean-Yves Lefrant, Christophe Guervilly, Gerald Chanques, Philippe Corne, Bernard Allaouchiche, Charlotte Le Goff, Samir Jaber, Olivier Jonquet, Passerieux, Emilie, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), CHU Marseille, 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), and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_treatment, Population, 030204 cardiovascular system & hematology, Buffers, Critical Care and Intensive Care Medicine, Severity of Illness Index, law.invention, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Patient Admission, law, medicine, Humans, Renal replacement therapy, Prospective Studies, Risk factor, education, Intensive care medicine, Prospective cohort study, Acidosis, Aged, education.field_of_study, Sodium bicarbonate, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Mortality rate, Research, Incidence, nutritional and metabolic diseases, 030208 emergency & critical care medicine, Proton Pump Inhibitors, Middle Aged, Prognosis, Intensive care unit, 3. Good health, Intensive Care Units, Sodium Bicarbonate, Treatment Outcome, chemistry, Emergency medicine, Female, medicine.symptom, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Introduction: In this study, we sought describe the incidence and outcomes of severe metabolic or mixed acidemia in critically ill patients as well as the use of sodium bicarbonate therapy to treat these illnesses. Methods: We conducted a prospective, observational, multiple-center study. Consecutive patients who presented with severe acidemia, defined herein as plasma pH below 7.20, were screened. The incidence, sodium bicarbonate prescription and outcomes of either metabolic or mixed severe acidemia were analyzed. Results: Among 2, 550 critically ill patients, 200 (8%) presented with severe acidemia, and 155 (6% of the total admissions) met the inclusion criteria. Almost all patients needed mechanical ventilation and vasopressors during their ICU stay, and 20% of them required renal replacement therapy within the first 24 hours of their ICU stay. Severe metabolic or mixed acidemia was associated with a mortality rate of 57% in the ICU. Delay of acidemia recovery as opposed to initial pH value was associated with increased mortality in the ICU. The type of acidemia did not influence the decision to administer sodium bicarbonate. Conclusions: The incidence of severe metabolic or mixed acidemia in critically ill patients was 6% in the present study, and it was associated with a 57% mortality rate in the ICU. In contradistinction with the initial acid-base parameters, the rapidity of acidemia recovery was an independent risk factor for mortality. Sodium bicarbonate prescription was very heterogeneous between ICUs. Further studies assessing specific treatments may be of interest in this population.
Published: 2011

16. Prognostic value of the expression of C-Chemokine Receptor 6 and 7 and their ligands in non-metastatic breast cancer

Author: Philippe A. Cassier, Nathalie Bendriss-Vermare, Olivier Tredan, Jean-Yves Blay, Isabelle Treilleux, Christophe Caux, Hervé Mignotte, Thomas Bachelot, Christine Ménétrier-Caux, Isabelle Ray-Coquard, Clarisse Bathélémy-Dubois, Serge Lebecque, Sophie Goddard-Léon, Jean-Jacques Pin, BMC, Ed., Département de Médecine Nucléaire, Centre Léon Bérard [Lyon], 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), Département de Biopathologie, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Département de Chirurgie cancérologique, Innate Pharma, and This work was supported by grants from the Breast Cancer Research Foundation, from La Ligue contre le Cancer, comité de la Savoie et du Rhône and Shering Plough Research Institute
Subjects: Oncology, Adult, Receptors, CCR6, medicine.medical_specialty, Cancer Research, Receptors, CCR7, C-C chemokine receptor type 7, [SDV.CAN]Life Sciences [q-bio]/Cancer, chemical and pharmacologic phenomena, Breast Neoplasms, C-C chemokine receptor type 6, Ligands, lcsh:RC254-282, Metastasis, Chemokine receptor, Breast cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Genetics, metastasis, Humans, early breast cancer, Aged, Aged, 80 and over, business.industry, CCL19, chemokine, chemokine receptor, hemic and immune systems, Middle Aged, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Prognosis, Survival Analysis, Chemokines, C, CCL20, Gene Expression Regulation, Neoplastic, Lymphatic Metastasis, metastasi, Female, Lymph Nodes, Stromal Cells, business, CCL21, Research Article
Abstract: Background Chemokines and chemokine receptors are major actors of leukocytes trafficking and some have been shown to play an important role in cancer metastasis. Chemokines CCL19, CCL20 and CCL21 and their receptors CCR6 and CCR7, were assessed as potential biomarkers of metastatic dissemination in primary breast cancer. Methods Biomarker expression levels were evaluated using immunohistochemistry on paraffin-embedded tissue sections of breast cancer (n = 207). Results CCR6 was expressed by tumor cells in 35% of cases. CCR7 was expressed by spindle shaped stromal cells in 43% of cases but not by tumor cells in this series. CCL19 was the only chemokine found expressed in a significant number of breast cancers and was expressed by both tumor cells and dendritic cells (DC). CCR6, CCL19 and CCR7 expression correlated with histologic features of aggressive disease. CCR6 expression was associated with shorter relapse-free survival (RFS) in univariate and but not in multivariate analysis (p = 0.0316 and 0.055 respectively), and was not associated with shorter overall survival (OS). Expression of CCR7 was not significantly associated with shorter RFS or OS. The presence of CCL19-expressing DC was associated with shorter RFS in univariate and multivariate analysis (p = 0.042 and 0.020 respectively) but not with shorter OS. Conclusion These results suggest a contribution of CCR6 expression on tumor cells and CCL19-expressing DC in breast cancer dissemination. In our series, unlike what was previously published, CCR7 was exclusively expressed on stromal cells and was not associated with survival.
Published: 2011

17. Impact of a multifaceted program to prevent postoperative delirium in the elderly: the CONFUCIUS stepped wedge protocol

Author: Damien Heitz, Antoine Duclos, Marc Bonnefoy, P. Rippert, Brigitte Comte, Thomas Fassier, Christelle Mouchoux, Pierre Krolak-Salmon, Cyrille Colin, Pharmacie, Hospices Civils de Lyon (HCL)-Hôpital des Charpennes [CHU - HCL], Hospices Civils de Lyon (HCL), 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), Université de Lyon-Université Lumière - Lyon 2 (UL2), Pôle Information Médicale Evaluation Recherche (IMER), Service de médecine gériatrique, Hospices Civils de Lyon (HCL)-Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), 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)-Hôpital Edouard Herriot [CHU - HCL], Pôle de Gériatrie, CHU Strasbourg, Hôpital des Charpennes [CHU - HCL], Dynamique Cérébrale et Cognition, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), The CONFUCIUS study is funding by the National French Program of Hospital Quality Research (Programme de Recherche en Qualité Hospitalière), 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), 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), Santé Individu Société (SIS), 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), 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), and BMC, Ed.
Subjects: medicine.medical_specialty, Postoperative Complications/prevention & control, medicine.medical_treatment, MEDLINE, Psychological intervention, lcsh:Geriatrics, Disease cluster, law.invention, 03 medical and health sciences, Study Protocol, 0302 clinical medicine, Postoperative Complications, Randomized controlled trial, law, Intervention (counseling), mental disorders, medicine, Cluster Analysis, Humans, 030212 general & internal medicine, Cluster randomised controlled trial, Postoperative Period, Geriatry and gerontology, Aged, Aged, 80 and over, Patient Care Team, Rehabilitation, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, business.industry, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Postoperative Complications/psychology, Age Factors, Delirium, 3. Good health, lcsh:RC952-954.6, Delirium/prevention & control, Gériatrie et gérontologie, Physical therapy, Delirium/psychology, Geriatrics and Gerontology, medicine.symptom, business, Patient Care Team/trends, 030217 neurology & neurosurgery
Abstract: Background Postoperative delirium is common in the elderly and is associated with a significant increase in mortality, complications, length of hospital stay and admission in long care facility. Although several interventions have proved their effectiveness to prevent it, the Cochrane advises an assessment of multifaceted intervention using rigorous methodology based on randomized study design. Our purpose is to present the methodology and expected results of the CONFUCIUS trial, which aims to measure the impact of a multifaceted program on the prevention of postoperative delirium in elderly. Method/Design Study design is a stepped wedge cluster randomized trial within 3 surgical wards of three French university hospitals. All patients aged 75 and older, and admitted for scheduled surgery will be included. The multifaceted program will be conducted by mobile geriatric team, including geriatric preoperative consultation, training of the surgical staff and implementation of the Hospital Elder Life Program, and morbidity and mortality conference related to delirium cases. The primary outcome is based on postoperative delirium rate within 7 days after surgery. This program is planned to be implemented along four successive time periods within all the surgical wards. Each one will be affected successively to the control arm and to the intervention arm of the trial and the order of program introduction within each surgical ward will be randomly assigned. Based on a 20% reduction of postoperative delirium rate (ICC = 0.25, α = 0.05, β = 0.1), three hundred sixty patients will be included i.e. thirty patients per service and per time period. Endpoints comparison between intervention and control arms of the trial will be performed by considering the cluster and time effects. Discussion Better prevention of delirium is expected from the multifaceted program, including a decrease of postoperative delirium, and its consequences (mortality, morbidity, postoperative complications and length of hospital stay) among elderly patients. This study should allow better diagnosis of delirium and strengthen the collaboration between surgical and mobile geriatric teams. Should the program have a substantial impact on the prevention of postoperative delirium in elderly, it could be extended to other facilities. Trial registration ClinicalTrials.gov: NCT01316965
Published: 2011

18. Determination of the myocardial area at risk after reperfused acute myocardial infarction with different imaging techniques: cardiac magnetic resonance imaging, multidetector computed tomography and histopathological validation

Author: Stanislas Rapacchi, Didier Revel, Lionel Augeul, Pierre Croisille, Loic Boussel, Nathan Mewton, Joseph Loufouat, Michel Ovize, René Ferrera, Gilles Rioufol, Hôpital Cardiovasculaire Louis Pradel, Hospices Civils de Lyon ( HCL ), 5 - RMN et optique : De la mesure aux biomarqueurs, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé ( CREATIS ), 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 ) -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 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 ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Cardioprotection, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Recherche et d'Application en Traitement de l'Image et du Signal ( CREATIS ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -École Supérieure Chimie Physique Électronique 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), RMN et optique : De la mesure au biomarqueur, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), 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)-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 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)-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-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche et d'Application en Traitement de l'Image et du Signal (CREATIS), 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 National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), BMC, Ed., Institut National des Sciences Appliquées (INSA)-Université de Lyon-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 Claude Bernard Lyon 1 (UCBL), Institut National des Sciences Appliquées (INSA)-Université de Lyon-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), and Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: lcsh:Diseases of the circulatory (Cardiovascular) system, medicine.medical_specialty, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Area at risk, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Cardiac magnetic resonance imaging, Multidetector computed tomography, medicine, Radiology, Nuclear Medicine and imaging, Myocardial infarction, ComputingMilieux_MISCELLANEOUS, [ SDV.IB.IMA ] Life Sciences [q-bio]/Bioengineering/Imaging, Angiology, Medicine(all), Radiological and Ultrasound Technology, medicine.diagnostic_test, business.industry, [ SDV.MHEP.CSC ] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Infarct size, medicine.disease, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Angioplasty balloon, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, lcsh:RC666-701, Oral Presentation, Radiology, Imaging technique, Cardiology and Cardiovascular Medicine, business
Abstract: The myocardial area at risk (AAR) is a major determinant of infarct size. Which imaging technique is the most appropriate to accurately measure its size remains debated.
Published: 2011

19. Strategies of initiation and streamlining of antibiotic therapy in 41 French intensive care units

Author: Philippe Montravers, Herve Dupont, Remy Gauzit, Benoit Veber, Jean-Pierre Bedos, Alain Lepape, The CIAR Study Group, Service d'anesthésie - réanimation chirurgicale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Pôle d'Anesthésie Réanimation, CHU Amiens-Picardie, Affectations Mineralisantes du Systeme Cardiovasculaire : Calcifications Arterielles et Valvulaires Aortiques, Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'anesthésie-réanimation [Hôtel-Dieu], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Hôtel-Dieu [Paris], Service de réanimation médicale [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de réanimation [CH Versailles], Centre Hospitalier de Versailles André Mignot (CHV), 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), This research was supported by Wyeth Pharmaceuticals France, CIAR (Club d'infectiologie en Anesthésie-Réanimation) Study Group, Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Université de Picardie Jules Verne ( UPJV ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Hôtel-Dieu [Paris], Service de réanimation médicale [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Service de Reanimation Polyvalente, Centre Hospitalier de Versailles (CHV), Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, and BMC, Ed.
Subjects: Male, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], MESH : Prospective Studies, MESH : Aged, Bacteremia, Critical Care and Intensive Care Medicine, MESH : Intensive Care, MESH : Intraabdominal Infections, law.invention, MESH: Clinical Protocols, MESH : Physician's Practice Patterns, 0302 clinical medicine, Clinical Protocols, law, MESH: Risk Factors, Risk Factors, MESH : Female, 030212 general & internal medicine, Hospital Mortality, Prospective Studies, MESH : Anti-Bacterial Agents, Practice Patterns, Physicians', Prospective cohort study, MESH: Bacteremia, MESH: Aged, MESH: Intraabdominal Infections, MESH: Middle Aged, [ SDV.MHEP.PHY ] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], MESH : After-Hours Care, MESH : Adult, Middle Aged, MESH : Risk Factors, Intensive care unit, 3. Good health, Anti-Bacterial Agents, Intensive Care Units, SAPS II, Cohort, SOFA score, Female, France, MESH : Intensive Care Units, MESH: After-Hours Care, Adult, medicine.medical_specialty, MESH: Pneumonia, Critical Care, MESH : Male, MESH : Drug Administration Schedule, MESH: Drug Administration Schedule, Drug Administration Schedule, MESH : Hospital Mortality, 03 medical and health sciences, After-Hours Care, Intensive care, MESH: Anti-Bacterial Agents, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, MESH : Middle Aged, MESH : Clinical Protocols, MESH: Intensive Care, MESH: Hospital Mortality, MESH : France, MESH: Physician's Practice Patterns, Aged, MESH: Humans, business.industry, MESH : Pneumonia, Research, MESH : Humans, 030208 emergency & critical care medicine, MESH: Adult, Odds ratio, Pneumonia, MESH : Bacteremia, medicine.disease, MESH: Male, MESH: Prospective Studies, MESH: France, Emergency medicine, Intraabdominal Infections, MESH: Intensive Care Units, business, MESH: Female
Abstract: CIAR (Club d'infectiologie en Anesthésie-Réanimation) Study Group: Pr B Allaouchiche (HCL, CHU Lyon), Pr C Arich (CHU Nimes), Pr C Auboyer (CHU St-Etienne), Dr JP Caramella (CHG Nevers), Dr JF Cochard (CHU Bordeaux), Dr A Combes (CHG Meaux), Dr P Courant (CHG Avignon), Dr J Durand-Gasselin (CHG Toulon), Pr J Duranteau (APHP, CHU Bicetre), Dr H Floch (CHU Nantes), Dr F Fraisse (CHG St Denis), Pr M Freysz (CHU Dijon), Dr B Garrigues (CHG Aix-en-Provence), Dr B Georges (CHU Toulouse), Pr F Gouin (APHM, CHU Marseille), Pr L Jacob (APHP, CHU St Louis), Pr P Juvin (APHP, CHU Beaujon), Dr J Keinlen (CHU Montpellier), Dr AM Korinek (APHP, CHU Pitie Salpetriere), Dr C Lamer (Institut Mutualiste Montsouris, Paris), Pr JY Lefrant (CHU Nimes), Dr O Lesieur (CHG La Rochelle), Dr Yazine Mahjoub (CHU Amiens), Pr Y Malledant (CHU Rennes), Pr C Martin (APHM, CHU Marseille), Pr O Mimoz (CHU Poitiers), Pr C Paugam-Burtz (APHP, CHU Beaujon, Clichy), Dr PF Perrigault (CHU Montpellier), Pr T Pottecher (CHU Strasbourg), Pr JL Pourriat (APHP, CHU Hotel Dieu), Dr JF Poussel (CHG Metz), Dr A Rabbat (APHP, CHU Hotel Dieu), Dr J Reignier (CHG La Roche sur Yon), Dr P Sichel (CHG Cherbourg), Dr JP Sollet (CHG Argenteuil), Dr D Thevenin (CHG Lens), Dr G Viquesnel (CHU Caen).; International audience; INTRODUCTION: Few studies have addressed the decision-making process of antibiotic therapy (AT) in intensive care unit (ICU) patients. METHODS: In a prospective observational study, all consecutive patients admitted over a one-month period (2004) to 41 French surgical (n = 22) or medical/medico-surgical ICUs (n = 19) in 29 teaching university and 12 non-teaching hospitals were screened daily for AT until ICU discharge. We assessed the modalities of initiating AT, reasons for changes and factors associated with in ICU mortality including a specific analysis of a new AT administered on suspicion of a new infection. RESULTS: A total of 1,043 patients (61% of the cohort) received antibiotics during their ICU stay. Thirty percent (509) of them received new AT mostly for suspected diagnosis of pneumonia (47%), bacteremia (24%), or intra-abdominal (21%) infections. New AT was prescribed on day shifts (45%) and out-of-hours (55%), mainly by a single senior physician (78%) or by a team decision (17%). This new AT was mainly started at the time of suspicion of infection (71%) and on the results of Gram-stained direct examination (21%). Susceptibility testing was performed in 261 (51%) patients with a new AT. This new AT was judged inappropriate in 58 of these 261 (22%) patients. In ICUs with written protocols for empiric AT (n = 25), new AT prescribed before the availability of culture results (P = 0.003) and out-of-hours (P = 0.04) was more frequently observed than in ICUs without protocols but the appropriateness of AT was not different. In multivariate analysis, the predictive factors of mortality for patients with new AT were absence of protocols for empiric AT (adjusted odds ratio (OR) = 1.64, 95% confidence interval (95%CI): 1.01 to 2.69), age ≥60 (OR = 1.97, 95% CI: 1.19 to 3.26), SAPS II score >38 (OR = 2.78, 95% CI: 1.60 to 4.84), rapidly fatal underlying diseases (OR = 2.91, 95% CI: 1.52 to 5.56), SOFA score ≥6 (OR = 4.48, 95% CI: 2.46 to 8.18). CONCLUSIONS: More than 60% of patients received AT during their ICU stay. Half of them received new AT, frequently initiated out-of-hours. In ICUs with written protocols, empiric AT was initiated more rapidly at the time of suspicion of infection and out-of-hours. These results encourage the establishment of local recommendations for empiric AT.
Published: 2011

20. Hydroxychloroquine levels in patients with systemic lupus erythematosus: whole blood is preferable but serum levels also detect non-adherence

Author: Jean-Sébastien Hulot, Felix Ackermann, N. Costedoat-Chalumeau, Jérémie Sellam, Amar Smail, Claire Goulvestre, Jean-Emmanuel Kahn, François Chasset, Gaëlle Leroux, Laurent Perard, Patrice Cacoub, Karim Sacre, Du Le Thi Huong, Moez Jallouli, Olivier Fain, Lionel Galicier, Bouchra Asli, Noémie Jourde-Chiche, Michel Vidal, Véronique Le Guern, Frédéric Lioté, Jean-Charles Piette, Judith Cohen-Bittan, Xavier Mariette, O. Aumaître, Thomas Papo, Benoit Blanchet, Marie Allard, Pascale Ghillani-Dalbin, Jérôme Stirnemann, Nicolas Limal, Hélène Desmurs-Clavel, Zahir Amoura, Laurent Sailler, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Cibles Thérapeutiques et conception de médicaments (CiTCoM - UMR 8038), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Chimie médicinale et recherche translationnelle (ERL Inserm U1268), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hedi Chaker Hospital [Sfax], CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Université Sorbonne Paris Cité (USPC), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hopital Saint-Louis [AP-HP] (AP-HP), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, CHU Tenon [AP-HP], Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Service de Rhumatologie [CHU Lariboisière], Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Amiens-Picardie, Service de médecine interne [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre hospitalier Saint Joseph - Saint Luc [Lyon], Hospices Civils de Lyon (HCL), Hôpital Ambroise Paré [AP-HP], Université Paris-Saclay, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Hôpital Foch [Suresnes], CHU Saint-Antoine [AP-HP], Hôpitaux Universitaires de Genève (HUG), Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de néphrologie et transplantation rénale [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service d'Immunologie [CHU Pitié-Salpétrière], 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 dermatologie et allergologie [CHU Tenon], Centre National de Référence du Lupus Systémique, Syndrome des Anticorps Anti-phospholipides et Maladies Auto-immunes Systémiques Rares [CHU Pitié Salpêtrière], Service de Médecine Interne 2, maladies auto-immunes et systémiques [CHU Pitié-Salpêtrière], Institut E3M [CHU Pitié-Salpêtrière], 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut E3M [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), CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées, Service de médecine interne [CHU Saint-Antoine], Centre National de Référence Maladies auto-immunes Systémiques Rares [CHU Pitié-Salpêtrière], Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Service de Médecine Gériatrique [CHU Pitié-Salpêtrière], Service de rhumatologie [CHU Saint-Antoine], Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Institut E3M [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Purpan [Toulouse], 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Service de gériatrie [CHU Pitié-Salpêtrière], and Gestionnaire, Hal Sorbonne Université
Subjects: Serum, medicine.medical_specialty, lcsh:Diseases of the musculoskeletal system, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Systemic lupus erythematosus, Pharmacokinetics, Risk Factors, Internal medicine, medicine, Humans, Lupus Erythematosus, Systemic, In patient, 030212 general & internal medicine, Whole blood, 030203 arthritis & rheumatology, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, business.industry, Hydroxychloroquine, Drug monitoring, Rheumatology, Non adherence, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Adherence, Pharmacodynamics, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Antirheumatic Agents, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Patient Compliance, lcsh:RC925-935, business, medicine.drug, Research Article
Abstract: Background Hydroxychloroquine (HCQ) levels can be measured in both serum and whole blood. No cut-off point for non-adherence has been established in serum nor have these methods ever been compared. The aims of this study were to compare these two approaches and determine if serum HCQ cut-off points can be established to identify non-adherent patients. Methods HCQ levels were measured in serum and whole blood from 573 patients with systemic lupus erythematosus (SLE). The risk factors for active SLE (SLEDAI score > 4) were identified by multiple logistic regression. Serum HCQ levels were measured in 68 additional patients known to be non-adherent, i.e. with whole-blood HCQ Results The mean (± SD) HCQ levels were 469 ± 223 ng/mL in serum and 916 ± 449 ng/mL in whole blood. The mean ratio of serum/whole-blood HCQ levels was 0.53 ± 0.15. In the multivariate analysis, low whole-blood HCQ levels (P = 0.023), but not serum HCQ levels, were independently associated with active SLE. From the mean serum/whole-blood level ratio, a serum HCQ level of 106 ng/mL was extrapolated as the corresponding cut-off to identify non-adherent patients with a sensitivity of 0.87 (95% CI 0.76–0.94) and specificity of 0.89 (95% CI 0.72–0.98). All serum HCQ levels of patients with whole-blood HCQ below the detectable level ( Conclusions These data suggest that whole blood is better than serum for assessing the pharmacokinetic/pharmacodynamic relation of HCQ. Our results support the use of serum HCQ levels to assess non-adherence when whole blood is unavailable.
Published: 2020

21. Treatment of voluminous and complicated superficial slow-flow vascular malformations with sirolimus (PERFORMUS): protocol for a multicenter phase 2 trial with a randomized observational-phase design

Author: Valérie Gissot, Laurent Guibaud, Groupe de Recherche de la Société Française de Dermatologie Pédiatrique, Jean-Baptiste Woillard, Christine Chiaverini, Sébastien Barbarot, Catherine Droitcourt, Stéphanie Mallet, Bruno Giraudeau, Juliette Mazereeuw-Hautier, Dominique Goga, Ludovic Martin, Gérard Lorette, Jérôme Rollin, Denis Herbreteau, Didier Bessis, Yves Gruel, Baptiste Morel, Annabel Maruani, Sophie Leducq, Annie-Pierre Jonville-Béra, Anne Le Touze, Elsa Tavernier, Pierre Vabres, Olivia Boccara, Sophie Blaise, MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), 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)-Université de Nantes (UN), Service de dermatologie (CHRU de Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Clinical Investigation Center - INSERM 1415, CHU Necker - Enfants Malades [AP-HP], Centre de Référence National des Maladies Génétiques à Expression Cutanée (MAGEC), Service de Dermatologie, Département de dermatologie [CHU de Montpellier], Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Service de Dermatologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de dermatologie (CHU de Toulouse), CHU Toulouse [Toulouse], Service de dermatologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), Clinique de Médecine Vasculaire, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Service de Dermatologie [Rennes], CHU Pontchaillou [Rennes], Département de dermatologie, CHU Marseille, CHU Marseille, Service de Dermatologie [CHU Angers] (PXE - le PseudoXanthome Elastique), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service de pharmacologie clinique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours, Service de neuroradiologie [Tours], Service de chirurgie maxillo-faciale [CHRU Tours], Département de chirurgie pédiatrique [Clocheville University Hospital, Tours], CHRU Clocheville, CIC 1415 Centre d’Investigation Clinique, Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Radiologie [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université, Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de dermatologie [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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), CHU Dijon, Centre Hospitalier Universitaire [Grenoble] (CHU), PRES Université Nantes Angers Le Mans (UNAM), Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Université de Limoges (UNILIM)-CHU Limoges, Université de Tours (UT), Groupe de Recherche de la Societé Française de Dermatologie Pédiatrique., Rollin, Jérôme, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), 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), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Pediatrics, Time Factors, Vascular Malformations, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Medicine (miscellaneous), Study Protocol, 0302 clinical medicine, Quality of life, Sclerotherapy, Clinical endpoint, Multicenter Studies as Topic, Pharmacology (medical), Child, Lymphatic malformations, Children, Mammalian target of rapamycin inhibitors, Randomized Controlled Trials as Topic, lcsh:R5-920, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Age Factors, Vascular anomalies, Magnetic Resonance Imaging, 3. Good health, Lymphangiogenesis, Natural history, [SDV] Life Sciences [q-bio], Observational Studies as Topic, Treatment Outcome, 030220 oncology & carcinogenesis, Venous malformations, Female, France, lcsh:Medicine (General), Blood Flow Velocity, medicine.drug, medicine.medical_specialty, Adolescent, 03 medical and health sciences, Clinical Trials, Phase II as Topic, 030225 pediatrics, Coronary Circulation, medicine, Humans, Protein Kinase Inhibitors, Sirolimus, business.industry, Clinical trial, Randomized placebo-phase design, Observational study, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background Slow-flow superficial vascular malformations (VMs) are rare congenital anomalies that can be responsible for pain and functional impairment. Currently, we have no guidelines for their management, which can involve physical bandages, sclerotherapy, surgery, anti-inflammatory or anti-coagulation drugs or no treatment. The natural history is progressive and worsening. Mammalian target of rapamycin (mTOR) is a serine/threonine kinase that acts as a master switch in cell proliferation, apoptosis, metabolism and angio/lymphangiogenesis. Sirolimus directly inhibits the mTOR pathway, thereby inhibiting cell proliferation and angio/lymphangiogenesis. Case reports and series have reported successful use of sirolimus in children with different types of vascular anomalies, with heterogeneous outcomes. Objective The objective of this trial is to evaluate the efficacy and safety of sirolimus in children with complicated superficial slow-flow VMs. Methods/design This French multicenter randomized observational-phase, phase 2 trial aims to include 50 pediatric patients 6 to 18 years old who have slow-flow (lymphatic, venous or lymphatico-venous) voluminous complicated superficial VM. Patients will be followed up for 12 months. All patients will start with an observational period (no treatment). Then at a time randomly selected between month 4 and month 8, they will switch to the experimental period (switch time), when they will receive sirolimus until month 12. Each child will undergo MRI 3 times: at baseline, at the switch time, and at month 12. For both periods (observational and treatment), we will calculate the relative change in volume of the VM divided by the study period duration. This relative change weighted by the study period duration will constitute the primary endpoint. VM will be measured by MRI images, which will be centralized and interpreted by the same radiologist who will be blinded to the study period. Hence, each patient will be his/her own control. Secondary outcomes will include assessment of safety and efficacy by viewing standardized digital photographs and according to the physician, the patient or proxy; impact on quality of life; and evolution of biological makers (coagulation factors, vascular endothelial growth factor, tissue factor). Discussion The main benefit of the study will be to resolve uncertainty concerning the efficacy of sirolimus in reducing the volume of VMs and limiting related complications and the safety of the drug in children with slow-flow VMs. This trial design is interesting in these rare conditions because all included patients will have the opportunity to receive the drug and the physician can maintain it after the end of the protocol if is found efficient (which would not be the case in a classical cross-over study). Trial registration ClinicalTrials.gov Identifier: NCT02509468, first received: 28 July 2015. EU Clinical Trials Register EudraCT Number: 2015-001096-43. Electronic supplementary material The online version of this article (10.1186/s13063-018-2725-1) contains supplementary material, which is available to authorized users.
Published: 2018

22. Prevalence, risk factors for infection and subtype distribution of the intestinal parasite Blastocystis sp. from a large-scale multi-center study in France

Author: El Safadi, Dima, Cian, Amandine, Nourrisson, Céline, Pereira, Bruno, Morelle, Christelle, Bastien, Patrick, Bellanger, Anne-Pauline, Botterel, Françoise, Candolfi, Ermanno, Desoubeaux, Guillaume, Lachaud, Laurence, Morio, Florent, Pomares, Christelle, Rabodonirina, Meja, Wawrzyniak, Ivan, Delbac, Frédéric, Gantois, Nausicaa, Certad, Gabriela, Delhaes, Laurence, Poirier, Philippe, Viscogliosi, Eric, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Centre National de la Recherche Scientifique (CNRS), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut de Parasitologie et de Pathologie Tropicale (IPPTS), Université de Strasbourg (UNISTRA), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cibles et Médicaments des Infections et de l'Immunité (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Hospices Civils de Lyon (HCL), This work was supported by grants from the Programme Orientations Stratégiques from the University of Lille 2, the Fonds Hospitalier d’Aide à l’Emergence from the CHRU of Lille, the Centre National de la Recherche Scientifique and the Institut Pasteur of Lille. DES was supported by a PhD fellowship from the Conseil National de la Recherche Scientifique and the AZM & Saade Association and AC by a PhD fellowship from the University of Lille 2 and the Institut Pasteur of Lille., Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre d'Etude des Pathologies Respiratoires (CEPR), UMR 1100. Equipe 3 'Aérosolthérapie et biothérapies à visée respiratoire' (CEPR. Equipe 3), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Gabriel Montpied (CHU), Institut de Recherche pour le Développement (IRD [France-Sud])-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Centre d'Etude des Pathologies Respiratoires (CEPR), UMR 1100. Equipe 3 (CEPR. Equipe 3), and COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)
Subjects: Adult, Male, Blastocystis sp, Adolescent, Intestinal parasite, Blastocystis Infections, Subtyping, Feces, Young Adult, Risk Factors, Prevalence, Animals, Humans, Child, Aged, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, Aged, 80 and over, Infant, Middle Aged, Infectious Diseases, PCR, Cross-Sectional Studies, Molecular epidemiology, Child, Preschool, Blastocystis, Risk factors for infection, Female, France, Research Article
Abstract: Background Blastocystis sp. is the most common intestinal parasite of humans. Despite its potential public health impact, epidemiological data regarding the prevalence and molecular subtype distribution of Blastocystis sp. in Europe are rarely reported. Therefore, the first multi-center epidemiological survey performed in Europe was conducted in France to diagnose and subtype Blastocystis sp. and to identify risk factors for infection. Methods Stool samples from 788 patients were collected either in summer or winter in 11 hospitals throughout France together with patient data. All stool samples were tested for the presence of Blastocystis sp. by quantitative PCR targeting the SSU rDNA gene. Positive samples were sequenced to determine the distribution of the subtypes in our cohort. Statistical analyses were performed to identify potential risk factors for infection. Results Using quantitative PCR, the overall prevalence of Blastocystis sp. was shown to reach 18.1 %. The prevalence was significantly higher in summer (23.2 %) than in winter (13.7 %). Travellers or subjects infected with other enteric parasites were significantly more infected by Blastocystis sp. than non-travellers or subjects free of other enteric parasites, respectively. Different age-related epidemiological patterns were also highlighted from our data. The prevalence of Blastocystis sp. was not significantly higher in patients with digestive symptoms or diagnosed with chronic bowel diseases. Among symptomatic patients, Blastocystis sp. infection was significantly associated with abdominal pain. Gender, socioeconomic status, and immune status were not identified as potential risk factors associated with infection. Among a total of 141 subtyped isolates, subtype 3 was predominant (43.3 %), followed by subtype 1 and subtype 4 (20 %), subtype 2 (12.8 %), subtype 6 and subtype 7 (2.1 %). No association between ST and clinical symptoms was statistically evidenced. Conclusions A high prevalence of Blastocystis sp. infection was found in our French patient population. Seasonal impact on the prevalence of Blastocystis sp. was highlighted and recent travels and age were identified as main risk factors for infection. Most cases were caused by subtypes 1 to 4, with a predominance of subtype 3. Large variations in both prevalence and ST distribution between hospitals were also observed, suggesting distinct reservoirs and transmission sources of the parasite. Electronic supplementary material The online version of this article (doi:10.1186/s12879-016-1776-8) contains supplementary material, which is available to authorized users.
Published: 2016

23. Assessment of the contribution of morbidity and mortality conferences to quality and safety improvement: a survey of participants’ perceptions

Author: Alizé Guyomard, Frédéric Prate, Gwenaëlle Vidal-Trecan, Arnaud Seigneurin, André Lecoanet, Jean-François Quaranta, Elodie Sellier, Patrice François, Université Nice Sophia Antipolis - Faculté de Médecine (UNS UFR Médecine), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Centre Hospitalier Universitaire de Nice, Centre Hospitalier Universitaire de Nice (CHU Nice), Techniques pour l'Evaluation et la Modélisation des Actions de la Santé (TIMC-IMAG-ThEMAS), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service de Biostatistiques [Lyon], Hospices Civils de Lyon (HCL), Biologie Computationnelle et Mathématique (TIMC-IMAG-BCM), Genomic Research Laboratory, Geneva University Hospital (HUG), and SELLIER, ELODIE
Subjects: Male, medicine.medical_specialty, Quality management, Attitude of Health Personnel, media_common.quotation_subject, Health informatics, Health administration, 03 medical and health sciences, Patient safety, Hospital, 0302 clinical medicine, Perception, Surveys and Questionnaires, mental disorders, medicine, Humans, Quality (business), 030212 general & internal medicine, Mortality, Hospitals, Teaching, ComputingMilieux_MISCELLANEOUS, media_common, Quality of Health Care, Morbidity and mortality conferences, business.industry, 030503 health policy & services, Public health, Nursing research, Health Policy, Consumer Behavior, Quality Improvement, 3. Good health, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Family medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Morbidity, 0305 other medical science, business, Attitude to Health, Research Article
Abstract: Background Evidence for the effectiveness of the morbidity and mortality conferences in improving patient safety is lacking. The aim of this survey was to assess the opinion of participants concerning the benefits and the functioning of morbidity and mortality conferences, according to their organizational characteristics. Methods We conducted a survey of professionals involved in a morbidity and mortality conference using a self-administered questionnaire in three French teaching hospitals in 2012. The questionnaire focused on the functioning of morbidity and mortality conferences, the perceived benefits, the motivations of participants, and how morbidity and mortality conferences could be improved. The perception of participants was analysed according to the characteristics of morbidity and mortality conferences. Results A total of 698 participants in 54 morbidity and mortality conferences completed the questionnaire. Most of them (91 %) were satisfied with how the morbidity and mortality conference they attended was conducted. The improvements in healthcare quality and patient safety were the main benefits perceived by participants. Effectiveness in improving safety was mainly perceived when cases were thoroughly analysed (adjusted odds ratio [a0R] =2.31 [1.14–4.66]). The existence of a written charter (p = 0.05), the use of a standardized case presentation (p = 0.049), and prior dissemination of the meeting agenda (p = 0.02) were also associated with the perception of morbidity and mortality conference effectiveness. The development and achievement of improvement initiatives were associated with morbidity and mortality conferences perceived as being more effective (p
Published: 2016

24. Exploring the link between MORF4L1 and risk of breast cancer

Author: Martrat, G., Maxwell, C.A., Tominaga, E., Porta-de-la-Riva, M., Bonifaci, N., Gomez-Baldo, L., Bogliolo, M., Lazaro, C., Blanco, I., Brunet, J., Aguilar, H., Fernandez-Rodriguez, J., Seal, S., Renwick, A., Rahman, N., Kuhl, J., Neveling, K., Schindler, D., Ramirez, M.J., Castella, M., Hernandez, G., Easton, D.F., Peock, S., Cook, M., Oliver, C.T., Frost, D., Platte, R., Evans, D.G., Lalloo, F., Eeles, R., Izatt, L., Chu, C., Davidson, R., Ong, K.R., Cook, J., Douglas, F., Hodgson, S., Brewer, C., Morrison, P.J., Porteous, M., Peterlongo, P., Manoukian, S., Peissel, B., Zaffaroni, D., Roversi, G., Barile, M., Viel, A., Pasini, B., Ottini, L., Putignano, A.L., Savarese, A., Bernard, L., Radice, P., Healey, S., Spurdle, A., Chen, X.Q., Beesley, J., Rookus, M.A., Verhoef, S., Tilanus-Linthorst, M.A., Vreeswijk, M.P., Asperen, C.J., Bodmer, D., Ausems, M.G.E.M., Os, T.A. van, Blok, M.J., Meijers-Heijboer, H.E.J., Hogervorst, F.B.L., Goldgar, D.E., Buys, S., John, E.M., Miron, A., Southey, M., Daly, M.B., Harbst, K., Borg, A., Rantala, J., Barbany-Bustinza, G., Ehrencrona, H., Stenmark-Askmalm, M., Kaufman, B., Laitman, Y., Milgrom, R., Friedman, E., Domchek, S.M., Nathanson, K.L., Rebbeck, T.R., Oskar, T., Couch, F.J., Wang, X.S., Fredericksen, Z., Cuadras, D., Moreno, V., Pientka, F.K., Depping, R., Caldes, T., Osorio, A., Benitez, J., Bueren, J., Heikkinen, T., Nevanlinna, H., Hamann, U., Torres, D., Caligo, M.A., Godwin, A.K., Imyanitov, E.N., Janavicius, R., Sinilnikova, O.M., Stoppa-Lyonnet, D., Mazoyer, S., Verny-Pierre, C., Castera, L., Pauw, A. de, Bignon, Y.J., Uhrhammer, N., Peyrat, J.P., Vennin, P., Ferrer, S.F., Collonge-Rame, M.A., Mortemousque, I., McGuffog, L., Chenevix-Trench, G., Pereira-Smith, O.M., Antoniou, A.C., Ceron, J., Tominaga, K., Surralles, J., Pujana, M.A., EMBRACE, kConFab, HEBON, BCFR, SWE-BRCA, GEMO Study Collaborators, Human Genetics, BMC, Ed., Translational Research Laboratory, Catalan Institute of Oncology-Bellvitge Institute for Biomedical Research, Biomedical Research Centre Network for Epidemiology and Public Health (CIBERESP), Catalan Institute of Oncology, Department of Cellular and Structural Biology, The University of Texas Health Science Center at Houston (UTHealth)-Sam and Ann Barshop Institute for Longevity and Aging Studies, Chemoresistance and Predictive Factors of Tumor Response and Stromal Microenvironment, Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Biomarkers and Susceptibility Unit, Department of Genetics and Microbiology, Universitat Autònoma de Barcelona (UAB), Biomedical Research Centre Network for Rare Diseases (CIBERER), Genetic Counseling and Hereditary Cancer Programme, Section of Cancer Genetics, Institute of cancer research, Department of Human Genetics, Julius-Maximilians-Universität Würzburg (JMU), Strangeways Research Laboratory, University of Cambridge [UK] (CAM)-Department of Public Health and Primary Care-Centre for Cancer Genetic Epidemiology, Centre for Cancer Genetic Epidemiology [Cambridge], University of Cambridge [UK] (CAM)-Department of Oncology, Genetic Medicine, St Mary's Hospital-NHS Foundation Trust-Manchester Academic Health Sciences Centre-Central Manchester University Hospitals, Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Clinical Genetics Department, Guy's and St Thomas NHS Foundation Trust, Yorkshire Regional Genetics Service, St James's hospital, Ferguson-Smith Centre for Clinical Genetics, West Midlands Regional Genetics Service, Birmingham Women's and Children's NHS Foundation Trust, Sheffield Clinical Genetics Service, Sheffield Children's NHS Foundation Trust, Institute of Human Genetics, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Queen Mary University of London (QMUL)-St George's Hospital, Department of Clinical Genetics, Royal Devon & Exeter Hospital, Northern Ireland Regional Genetics Centre, Belfast City Hospital, South East of Scotland Regional Genetics Service, Western General Hospital, Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine-Fondazione IRCCS Istituto Nazionale Tumori (INT), Department of Preventive and Predictive Medicine, IFOM, Istituto FIRC di Oncologia Molecolare (IFOM), Unit of Medical Genetics, Fondazione IRCCS INT, Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia (IEO), Division of Experimental Oncology 1, Centro di Riferimento Oncologico (CRO), Department of Genetics, Biology and Biochemistry, Università degli studi di Torino = University of Turin (UNITO), Department of Molecular Medicine, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Università degli Studi di Firenze = University of Florence (UniFI), Fiorgen Foundation for Pharmacogenomics, Division of Medical Oncology, Regina Elena Cancer Institute, Department of Experimental Oncology, IEO, Division of Genetics and Population Health, Queensland Institute of Medical Research, Department of Epidemiology, The Netherlands Cancer Institute, Family Cancer Clinic, Department of Surgical Oncology, Erasmus University Medical Center [Rotterdam] (Erasmus MC)-Family Cancer Clinic, Center for Human and Clinical Genetics, Leiden University Medical Center (LUMC), DNA Diagnostics, Radboud University Medical Center [Nijmegen], Department of Medical Genetics, University Medical Center [Utrecht], Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), University Hospital Maastricht, VU Medical Center, Department of Dermatology, University of Utah School of Medicine [Salt Lake City], Department of Internal Medicine, Huntsman Cancer Institute, Cancer Prevention Institute of California, Department of Cancer Biology, Dana-Farber Cancer Institute [Boston], Department of Surgery, Harvard Medical School [Boston] (HMS), Centre for Molecular, Environmental, Genetic and Analytic Epidemiology (MEGA), University of Melbourne-Melbourne School of Population Health, Division of Population Science, Fox Chase Cancer Center, Department of Oncology, Clinical Sciences, Lund University [Lund]-Skåne University Hospital, Karolinska University Hospital [Stockholm], Department of Genetics and Pathology, Uppsala University, Department of Oncology, University Hospital-Hälsouniversitetet Universitetssjukhuset, The Institute of Oncology, Chaim Sheba Medical Center, The Susanne Levy Gertner Oncogenetics Unit, Sackler Faculty of Medicine, Tel Aviv University (TAU), Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania-University of Pennsylvania, Department of Medicine, Medical Genetics, Abramson Cancer Center-Perelman School of Medicine, Center for Clinical Epidemiology and Biostatistics, Faculty of Medicine, University of Iceland [Reykjavik], Department of Laboratory Medicine and Pathology, Mayo Clinic, Department of Health Sciences Research, Statistical Assessment Service, Department of Physiology, Universität zu Lübeck = University of Lübeck [Lübeck]-Center for Structural and Cell Biology in Medicine, Medical Oncology Branch, Hospital Clínico San Carlos, Human Cancer Genetics Programme, CIBER de Enfermedades Raras (CIBERER)-Spanish National Cancer Research Centre, Division of Hematopoiesis and Gene Therapy, Centro de Investigaciones Energéticas Medioambientales y Tecnológicas [Madrid] (CIEMAT), Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Molecular Genetics of Breast Cancer, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Instituto de Genética Humana, Pontificia Universidad Javeriana (PUJ), Section of Genetic Oncology, University of Pisa - Università di Pisa, Department of Pathology and Laboratory Medicine, University of Kansas Medical Center [Kansas City, KS, USA], Laboratory of Molecular Oncology, N.N. Petrov Institute of Oncology, Department of Molecular and Regenerative Medicine, Hematology, Oncology and Transfusion, Vilnius University [Vilnius]-Hospital Santariskiu Clinics, Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Léon Bérard [Lyon]-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), Service de Génétique Oncologique, Institut Curie [Paris], 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), Département d'Oncogénétique, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER-UNICANCER, Laboratoire d'Oncologie Moléculaire Humaine, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER, Consultation d'Oncogénétique, Laboratoire de Génétique Chromosomique, CH Chambéry, Département de Génétique et Reproduction, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques, Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, The CIMBA data management is supported by Cancer Research - UK., kConFab, HEBON, BCFR, SWE-BRCA, GEMO Study Collaborators, Autonomous University of Barcelona, Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), Department of Oncology-University of Cambridge [UK] (CAM), University of Turin, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Departament of Genetics and Pathology, Uppsala University-Rudbeck Laboratory, Tel Aviv University [Tel Aviv], University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], Universität zu Lübeck [Lübeck]-Center for Structural and Cell Biology in Medicine, University of Kansas Medical Center [Lawrence], Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER, Universiteit Leiden-Universiteit Leiden, Skåne University Hospital-Lund University [Lund], University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia]-Abramson Cancer Center, 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 Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Clinical Genetics, Faculteit der Geneeskunde, Klinische Genetica, RS: GROW - School for Oncology and Reproduction, Genetica & Celbiologie, Easton, Douglas [0000-0003-2444-3247], Antoniou, Antonis [0000-0001-9223-3116], Apollo - University of Cambridge Repository, Martrat, G, Maxwell, C, Tominaga, E, Porta de la Riva, M, Bonifaci, N, Gómez Baldó, L, Bogliolo, M, Lázaro, C, Blanco, I, Brunet, J, Aguilar, H, Fernández Rodríguez, J, Seal, S, Renwick, A, Rahman, N, Kühl, J, Neveling, K, Schindler, D, Ramírez, M, Castellà, M, Hernández, G, Embrace, Easton, D, Peock, S, Cook, M, Oliver, C, Frost, D, Platte, R, Evans, D, Lalloo, F, Eeles, R, Izatt, L, Chu, C, Davidson, R, Ong, K, Cook, J, Douglas, F, Hodgson, S, Brewer, C, Morrison, P, Porteous, M, Peterlongo, P, Manoukian, S, Peissel, B, Zaffaroni, D, Roversi, G, Barile, M, Viel, A, Pasini, B, Ottini, L, Putignano, A, Savarese, A, Bernard, L, Radice, P, Healey, S, Spurdle, A, Chen, X, Beesley, J, Rookus, M, Verhoef, S, Tilanus Linthorst, M, Vreeswijk, M, Asperen, C, Bodmer, D, Ausems, M, van Os, T, Blok, M, Meijers Heijboer, H, Hogervorst, F, Goldgar, D, Buys, S, John, E, Miron, A, Southey, M, Daly, M, Harbst, K, Borg, A, Rantala, J, Barbany Bustinza, G, Ehrencrona, H, Stenmark Askmalm, M, Kaufman, B, Laitman, Y, Milgrom, R, Friedman, E, Domchek, S, Nathanson, K, Rebbeck, T, Johannsson, O, Couch, F, Wang, X, Fredericksen, Z, Cuadras, D, Moreno, V, Pientka, F, Depping, R, Caldés, T, Osorio, A, Benítez, J, Bueren, J, Heikkinen, T, Nevanlinna, H, Hamann, U, Torres, D, Caligo, M, Godwin, A, Imyanitov, E, Janavicius, R, Sinilnikova, O, Stoppa Lyonnet, D, Mazoyer, S, Verny Pierre, C, Castera, L, de Pauw, A, Bignon, Y, Uhrhammer, N, Peyrat, J, Vennin, P, Ferrer, S, Collonge Rame, M, Mortemousque, I, Mcguffog, L, Chenevix Trench, G, Pereira Smith, O, Antoniou, A, Cerón, J, Tominaga, K, Surrallés, J, Pujana, M, Human genetics, CCA - Oncogenesis, Biomedical Research Centre Network for Epidemiology and Public Health ( CIBERESP ), The University of Texas Health Science Center at San Antonio-Sam and Ann Barshop Institute for Longevity and Aging Studies, Institut d'Investigació Biomèdica de Bellvitge [Barcelone] ( IDIBELL ), Biomedical Research Centre Network for Rare Diseases ( CIBERER ), University of Würzburg, University of Cambridge [UK] ( CAM ) -Department of Public Health and Primary Care-Centre for Cancer Genetic Epidemiology, University of Cambridge [UK] ( CAM ) -Department of Oncology, Birmingham Women's Hospital Healthcare NHS Trust, Sheffield Children's Hospital, Newcastle Upon Tyne Hospitals NHS Trust, Queen Mary University of London ( QMUL ) -St George's Hospital, IFOM, Istituto FIRC di Oncologia Molecolare ( IFOM ), Università degli Studi di Roma 'La Sapienza' [Rome], University of Florence, Erasmus MC-Daniel den Hoed Cancer Center-Family Cancer Clinic, University Medical Center Utrecht, Academic Medical Center [Amsterdam] ( AMC ), University of Amsterdam [Amsterdam] ( UvA ) -University of Amsterdam [Amsterdam] ( UvA ), Harvard Medical School [Boston] ( HMS ), Centre for Molecular, Environmental, Genetic and Analytic Epidemiology ( MEGA ), University of Pennsylvania School of Medicine, University of Pennsylvania School of Medicine-Abramson Cancer Center, Centro de Investigaciones Energéticas, Deutsches Krebsforschungszentrum ( DKFZ ), Pontificia Universidad Javeriana, University of Pisa [Pisa], University of Kansas Medical Center, Centre Léon Bérard [Lyon]-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 ), INSTITUT CURIE, Unité de génétique et biologie des cancers ( U830 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), CRLCC Jean Perrin, CRLCC Oscar Lambret, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques, Hôpital Bretonneau-CHRU Tours, and Universitat de Barcelona
Subjects: DNA Repair, Genes, BRCA2, RAD51, Genes, BRCA1, Germ-Cell, Helicase Brip1, medicine.disease_cause, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Mice, 0302 clinical medicine, Breast cancer, Fanconi anemia, Risk Factors, Replication Protein A, Teknik och teknologier, Homologous Recombination, skin and connective tissue diseases, C-Elegans, Genetics, Medicine(all), ddc:616, 0303 health sciences, Mutation, Fanconi Anemia Complementation Group D2 Protein, Nuclear Proteins, Anèmia aplàstica, 3. Good health, 030220 oncology & carcinogenesis, Chromodomain Protein, Engineering and Technology, Female, RNA Interference, Fanconi Anemia Complementation Group N Protein, Aplastic anemia, Research Article, BRCA2 Mutation Carrier, DNA repair, PALB2, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Cell Line, Càncer de mama, Genomic disorders and inherited multi-system disorders [IGMD 3], 03 medical and health sciences, SDG 3 - Good Health and Well-being, [SDV.CAN] Life Sciences [q-bio]/Cancer, Two-Hybrid System Techniques, medicine, Genetic predisposition, Animals, Humans, Genetic Predisposition to Disease, Caenorhabditis elegans, Gene, 030304 developmental biology, Phenocopy, Caenorhabditis-Elegan, Tumor Suppressor Proteins, medicine.disease, BRCA1, BRCA2, Pancreatic-Cancer, Fanconi Anemia, Genes, Cancer and Oncology, Fanconi-Anemia, Cancer research, Rad51 Recombinase, Susceptibility Gene, DNA Damage, Transcription Factors
Abstract: Introduction Proteins encoded by Fanconi anemia (FA) and/or breast cancer (BrCa) susceptibility genes cooperate in a common DNA damage repair signaling pathway. To gain deeper insight into this pathway and its influence on cancer risk, we searched for novel components through protein physical interaction screens. Methods Protein physical interactions were screened using the yeast two-hybrid system. Co-affinity purifications and endogenous co-immunoprecipitation assays were performed to corroborate interactions. Biochemical and functional assays in human, mouse and Caenorhabditis elegans models were carried out to characterize pathway components. Thirteen FANCD2-monoubiquitinylation-positive FA cell lines excluded for genetic defects in the downstream pathway components and 300 familial BrCa patients negative for BRCA1/2 mutations were analyzed for genetic mutations. Common genetic variants were genotyped in 9,573 BRCA1/2 mutation carriers for associations with BrCa risk. Results A previously identified co-purifying protein with PALB2 was identified, MRG15 (MORF4L1 gene). Results in human, mouse and C. elegans models delineate molecular and functional relationships with BRCA2, PALB2, RAD51 and RPA1 that suggest a role for MRG15 in the repair of DNA double-strand breaks. Mrg15-deficient murine embryonic fibroblasts showed moderate sensitivity to γ-irradiation relative to controls and reduced formation of Rad51 nuclear foci. Examination of mutants of MRG15 and BRCA2 C. elegans orthologs revealed phenocopy by accumulation of RPA-1 (human RPA1) nuclear foci and aberrant chromosomal compactions in meiotic cells. However, no alterations or mutations were identified for MRG15/MORF4L1 in unclassified FA patients and BrCa familial cases. Finally, no significant associations between common MORF4L1 variants and BrCa risk for BRCA1 or BRCA2 mutation carriers were identified: rs7164529, Ptrend = 0.45 and 0.05, P2df = 0.51 and 0.14, respectively; and rs10519219, Ptrend = 0.92 and 0.72, P2df = 0.76 and 0.07, respectively. Conclusions While the present study expands on the role of MRG15 in the control of genomic stability, weak associations cannot be ruled out for potential low-penetrance variants at MORF4L1 and BrCa risk among BRCA2 mutation carriers.

25. Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers

Author: Antoniou, Antonis C., Kuchenbaecker, Karoline B., Penny, Soucy, Jonathan, Beesley, Xiaoqing, Chen, Lesley, Mcguffog, Andrew, Lee, Daniel, Barrowdale, Sue, Healey, Sinilnikova, Olga M., Caligo, Maria A., Niklas, Loman, Katja, Harbst, Annika, Lindblom, Brita, Arver, Richard, Rosenquist, Per, Karlsson, Kate, Nathanson, Susan, Domchek, Tim, Rebbeck, Anna, Jakubowska, Jan, Lubinski, Katarzyna, Jaworska, Katarzyna, Durda, Zlowocka Perlowska, E., Elzbieta Złowowcka Perłowska, Ana, Osorio, Mercedes, Duran, Raquel, Andres, Javier, Benitez, Ute, Hamann, Hogervorst, Frans B., Van, A., Van Os, Theo A., Senno, Verhoef, Meijers Heijboer, Hanne E. J., Juul, Wijnen, Gomez Garcia, Encarna B., Ligtenberg, Marjolijn J., Mieke, Kriege, Margriet Collee, J., Margreet Gem Ausems, Oosterwijk, Jan C., Susan, Peock, Debra, Frost, Ellis, Steve D., Radka, Platte, Elena, Fineberg, Gareth Evans, D., Fiona, Lalloo, Chris, Jacobs, Ros, Eeles, Julian, Adlard, Rosemarie, Davidson, Trevor, Cole, Jackie, Cook, Joan, Paterson, Fiona, Douglas, Carole, Brewer, Shirley, Hodgson, Morrison, Patrick J., Lisa, Walker, Rogers, Mark T., Alan, Donaldson, Huw, Dorkins, Godwin, Andrew K., Betsy, Bove, Dominique Stoppa Lyonnet, Claude, Houdayer, Bruno, Buecher, De Pauw, A., Antoine Pauw, D. E., Sylvie, Mazoyer, Alain, Calender, Melanie, Leone, Brigitte Bressac De Paillerets, Olivier, Caron, Hagay, Sobol, Marc, Frenay, Fabienne, Prieur, Sandra, Ferrer, Isabelle, Mortemousque, Saundra, Buys, Mary, Daly, Alexander, Miron, Terry, Mb, Terry, Mu, Mary, Terry, Hopper, John L., John, Em, Esther, John M., Melissa, Southey, David, Goldgar, Singer, Christian F., Anneliese Fink Retter, Muy Kheng Tea, Geschwantler Kaulich, D., Daphne, Kaulich, Hansen, Thomas V. O., Nielsen, Finn C., Barkardottir, Rosa B., Mia, Gaudet, Tomas, Kirchhoff, Joseph, V., Joseph, Vijai, Ana Dutra Clarke, Kenneth, Offit, Marion, Piedmonte, Judy, Kirk, David, Cohn, Jean, Hurteau, John, Byron, James, Fiorica, Toland, Amanda E., Marco, Montagna, Cristina, Oliani, Evgeny, Imyanitov, Claudine, Isaacs, Laima, Tihomirova, Ignacio, Blanco, Conxi, Lazaro, Alex, Teule, Del Valle, J., Gayther, Simon A., Kunle, Odunsi, Jenny, Gross, Karlan, Beth Y., Edith, Olah, Soo Hwang Teo, Ganz, Patricia A., Beattie, Mary S., Dorfling, Cecelia M., Jansen Van Rensburg, E., Elizabeth Van Rensburg, Orland, Diez, Ava, Kwong, Schmutzler, Rita K., Barbara, Wappenschmidt, Christoph, Engel, Alfons, Meindl, Nina, Ditsch, Norbert, Arnold, Simone, Heidemann, Dieter, Niederacher, Sabine Preisler Adams, Dorothea, Gadzicki, Raymonda Varon Mateeva, Helmut, Deissler, Andrea, Gehrig, Christian, Sutter, Karin, Kast, Britta, Fiebig, Dieter, Schafer, Trinidad, Caldes, Miguel De La Hoya, Heli, Nevanlinna, Muranen, Taru A., Bernard, Lesperance, Spurdle, Amanda B., Neuhausen, Susan L., Ding, Yuan C., Xianshu, Wang, Zachary, Fredericksen, Pankratz, Vernon S., Lindor, Noralane M., Paolo, Peterlongo, Siranoush, Manoukian, Bernard, Peissel, Daniela, Zaffaroni, Bernardo, Bonanni, Loris, Bernard, Riccardo, Dolcetti, Laura, Papi, Ottini, Laura, Paolo, Radice, Greene, Mark H., Loud, Jennifer T., Andrulis, Irene L., Hilmi, Ozcelik, Anna, Mulligan, Gord, Glendon, Mads, Thomassen, Anne Marie Gerdes, Jensen, Uffe B., Anne Bine Skytte, Kruse, Torben A., Georgia Chenevix Trench, Couch, Fergus J., Jacques, Simard, Easton, Douglas F., Swedish Breast, Cancer Study S. B., Facility, Research H., Study, E., Collaborators, Study G., Investigators, K., Swe Brca Cimba, Embrace, Hebon, Study Gemo Collaborators, Kconfab, Investigators, BMC, Ed., Collaborative Oncological Gene-environment Study - COGS - - EC:FP7:HEALTH2009-05-01 - 2014-01-31 - 223175 - VALID, Centre for Cancer Genetic Epidemiology, University of Cambridge [UK] (CAM), Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec, Genetics and Population Health Division, Queensland Institute of Medical Research, Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Léon Bérard [Lyon]-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), Section of Genetic Oncology, University of Pisa - Università di Pisa, Department of Oncology, Lund University Hospital, Department of Clinical Genetics, Karolinska University Hospital [Stockholm], Department of Genetics and Pathology, Uppsala University-Rudbeck Laboratory, Sahlgrenska University Hospital [Gothenburg], Abramson Cancer Center, University of Pennsylvania-Perelman School of Medicine, University of Pennsylvania, International Hereditary Cancer Centre-Pomeranian Medical University [Szczecin] (PUM), Postgraduate School of Molecular Medicine, Warsaw Medical University, Human Genetics Group, Spanish National Cancer Research Centre, Biomedical Research Centre Network for Rare Diseases, CIBER de Enfermedades Raras (CIBERER), Institute of Biology and Molecular Genetics, Universidad de Valladolid [Valladolid] (UVa), Medical Oncology Division, Hospital Clínico de Zaragoza, Molecular Genetics of Breast Cancer, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Family Cancer Clinic, Netherlands Cancer Institute, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), VU Medical Center, Department of Clinical Genetics and GROM, School for Oncology and Developmental Biology, Department of Human Genetics, Radboud University [Nijmegen], Erasmus University Medical Center [Rotterdam] (Erasmus MC)-Family Cancer Clinic, Department of Clinical Molecular Genetics, University Medical Center [Utrecht], Department of Genetics, VU University Medical Center [Amsterdam], Genetic Medicine, Manchester Academic Health Sciences Centre-Central Manchester University Hospitals, Clinical Genetics, Guy's and St. Thomas' NHS Foundation Trust, Oncogenetics Team, The Institute of Cancer Research-Royal Marsden NHS Foundation Trust, Yorkshire Regional Genetics Service, Ferguson-Smith Centre for Clinical Genetics, Yorkhill Hospitals, West Midlands Regional Genetics Service, Birmingham Women's and Children's NHS Foundation Trust, Sheffield Clinical Genetics Service, Sheffield Children's NHS Foundation Trust, Addenbrookes Hospital, Institute of Human Genetics, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Royal Devon & Exeter Hospital, Medical Genetics Unit, University College of London [London] (UCL), Northern Ireland Regional Genetics Centre, Belfast Health and Social Care Trust, Department of Medical Genetics, Queen's University [Belfast] (QUB), Oxford Regional Genetics Service, Churchill Hospital Oxford Centre for Haematology, All Wales Medical Genetics Services, Singleton Hospital, Clinical Genetics Department, St Michael's Hospital, North West Thames Regional Genetics Service, Kennedy-Galton Centre, Department of Pathology and Laboratory Medicine, University of Kansas Medical Center [Kansas City, KS, USA], Clinical Molecular Genetics Laboratory, Fox Chase Cancer Center, Service de Génétique Oncologique, Institut Curie [Paris], 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), Service de génétique, Institut Gustave Roussy (IGR), Variabilité Génétique et Maladies Humaines, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Consultation de génétique, Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Service d'Oncologie Génétique, de Prévention et Dépistage, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Service de Génétique Clinique Chromosomique et Moléculaire, CHU Saint-Etienne, Laboratoire de Génétique Chromosomique, CH Chambéry, Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Department of Internal Medicine, Huntsman Cancer Institute, Division of Population Science, Department of Cancer Biology, Dana-Farber Cancer Institute [Boston], Department of Surgery, Harvard Medical School [Boston] (HMS), Department of Epidemiology, Columbia University [New York], Centre for Molecular , Environmental, Genetic and Analytic (MEGA) Epidemiology, University of Melbourne-Centre for Molecular, Melbourne School of Population Health, Cancer Prevention Institute of California, entre for Molecular, Environmental, Genetic and Analytic (MEGA) Epidemiology, University of Melbourne, Department of Dermatology, University of Utah School of Medicine [Salt Lake City], Dept of OB/GYN and Comprehensive Cancer Center, Medizinische Universität Wien = Medical University of Vienna, Center for Genomic Medicine, Copenhagen University Hospital-Rigshospitalet [Copenhagen], Copenhagen University Hospital, Department of Pathology, University of Iceland [Reykjavik]-Landspitali - University Hospital, Epidemiology Research Program, American Cancer Society, Department of Environmental Medicine, New York University School of Medicine, NYU System (NYU)-NYU System (NYU)-NYU Cancer Institute, Clinical Genetics Service, Memorial Sloane Kettering Cancer Center [New York], Statistical and Data Center, Roswell Park Cancer Institute [Buffalo], Australia New Zealand (ANZGOG), Westmead Hospital [Sydney], Ohio State University [Columbus] (OSU), Evanston CCOP - NorthShore University Health System, University of Chicago, Southern Pines Women's Health Center, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), Sarasota Memorial Healthcare, Tufts Medical Center, Department of Molecular Virology, Immunology and Medical Genetics [Colombus], Ohio State University [Columbus] (OSU)-College of Medicine and Public Health [Colombus], Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV - IRCCS, U.O.C. di Oncologia, Laboratory of Molecular Oncology, N.N. Petrov Institute of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University [Washington] (GU), Latvian Biomedical Research and Study Centre [Rīga], Genetic Counselling Unit, IDIBELL-Catalan Institute of Oncology, Molecular Diagnostic Unit, Department of Preventive Medicine, University of Southern California (USC)-Keck School of Medicine [Los Angeles], University of Southern California (USC), Department of Gynecologic Oncology, Women's Cancer Program, Samuel Oschin Comprehensive Cancer Institute, Department of Molecular Genetics, National Institute of Oncology, Cancer Research Initiatives Foundation, Sime Darby Medical Centre-Malaysia and University Malaya Cancer Research Institute-University Malaya Medical Centre, Jonsson Comprehensive Cancer Center at UCLA, Jonsson Comprehensive Cancer Center, UCSF Cancer Risk Program, University of California (UC), Departments of Medicine, Epidemiology, and Biostatistics, UCSF, Cancer Genetics Laboratory, University of Pretoria [South Africa], Oncogenetics Laboratory, Vall d'Hebron Institute of Oncology (VHIO), The Hong Kong Hereditary Breast Cancer Family Registry, The University of Hong Kong (HKU), Department of Gynaecology and Obstetrics, University Hospital of Cologne [Cologne]-Centre of Familial Breast and Ovarian Cancer-Centre for Integrated Oncology (CIO), Institute for Medical Informatics, Statistics and Epidemiology [Leipzig] (IMISE), Universität Leipzig [Leipzig], Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Ludwig-Maximilians-Universität München (LMU), University Hospital of Schleswig-Holstein-Christian-Albrechts-Universität zu Kiel (CAU), University Hospital Düsseldorf-Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Institute of Cell and Molecular Pathology, Hannover Medical School [Hannover] (MHH), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Universitätsklinikum Ulm - University Hospital of Ulm, Julius-Maximilians-Universität Würzburg (JMU)-Centre of Familial Breast and Ovarian Cancer, Heidelberg University Hospital [Heidelberg], University Hospital Carl Gustav Carus, Universität Regensburg (UR), University Hospital Frankfurt a.M., Molecular Oncology Laboratory, Hospital Clínico San Carlos, Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Hemato-oncology service, Hôpital du Sacré-Coeur de Montréal, Department of Population Sciences, Beckman Research Institute of City of Hope, Department of Laboratory Medicine and Pathology, Mayo Clinic, Unit of Molecular Bases of Genetic Risk and Genetic Testing, Fondazione IRCCS Istituto Nazionale Tumouri (INT)-Fondazione Istituto FIRC di Oncologia Molecolare, Unit of Medical Genetics, Fondazione IRCCS Istituto Nazionale Tumouri (INT), Division of Cancer Prevention and Genetics, Department of Experimental Oncology, Istituto Europeo di Oncologia-Consortium for Genomics Technology (Cogentech), Cancer Bioimmunotherapy Unit, IRCCS-Centro di Riferimento Oncologico, Università degli Studi di Firenze = University of Florence (UniFI), Department of Molecular Medicine, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Clinical Genetics Branch, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto-Cancer Care Ontario, Samuel Lunenfeld Research Institute, Mount Sinai Hospital [Toronto, Canada] (MSH), Department of Laboratory Medicine and Pathobiology, University of Toronto, Department of Laboratory Medicine, St Michael's Hospital-Keenan Research Centre of the Li Ka Shing Knowledge Institute [Toronto], Ontario Cancer Genetics Network, Cancer Care Ontario, Odense University Hospital, Department of Clinical Genetics [Copenhagen], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Skejby Hospital, Department of Laboratory Medicine and Pathology and Health Sciences Research, This work was supported by Cancer Research UK grants C12292/A11174 and C1287/A10118. The research leading to these results has received funding from the European Community's Seventh Framework Programme under grant agreement n° 223175 (HEALTH-F2-2009-223175), from the Canadian Institutes of Health Research for the 'CIHR Team in Familial Risks of Breast Cancer' program and by the Canadian Breast Cancer Research Alliance-grant #019511. This research was also supported by NIH grant CA128978, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a U.S. Department of Defence Ovarian Cancer Idea award (W81XWH-10-1-0341) and grants from the Breast Cancer Research Foundation and the Komen Foundation for the Cure. ACA is a CR-UK Senior Cancer Research Fellow, DFE is CR-UK Principal Research Fellow, GCT is a NHMRC Senior Principal Research Fellow, J.S. is Chairholder of the Canada Research Chair in Oncogenetics, on behalf of CIMBA, SWE-BRCA, HEBON, EMBRACE, GEMO Study Collaborators and kConFab Investigators, European Project: 223175,EC:FP7:HEALTH,FP7-HEALTH-2007-B,COGS(2009), Pediatric Surgery, Neurology, Medical Oncology, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Roswell Park Cancer Institute [Buffalo] (RPCI), Universität Leipzig, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Pennsylvania [Philadelphia]-Perelman School of Medicine, University of Pennsylvania [Philadelphia], Pomeranian Medical University-International Hereditary Cancer Centre, Radboud university [Nijmegen], University of Kansas Medical Center [Lawrence], Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Georgetown University, University of California, Westfälische Wilhelms-Universität Münster (WWU), Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU)-Centre of Familial Breast and Ovarian Cancer, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], RS: GROW - School for Oncology and Reproduction, Genetica & Celbiologie, Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Human Genetics, CCA -Cancer Center Amsterdam, ARD - Amsterdam Reproduction and Development, Human genetics, and CCA - Oncogenesis
Subjects: Oncology, Medicin och hälsovetenskap, Estrogen receptor, Genome-wide association study, HORMONE-RELATED PROTEIN, Chromosomes, Human, Pair 9 - genetics, Medical and Health Sciences, 0302 clinical medicine, 610 Medical sciences Medicine, CDKN2A, Risk Factors, Genotype, INVESTIGATORS, Chromosomes, Human, Pair 12 - genetics, skin and connective tissue diseases, MAMMOGRAPHIC DENSITY, Medicine(all), 0303 health sciences, BRCA1 Protein, Middle Aged, BRCA2 Protein, 3. Good health, DNA-Binding Proteins, Hereditary Breast and Ovarian Cancer Syndrome - genetics, 030220 oncology & carcinogenesis, Hereditary Breast and Ovarian Cancer Syndrome, TUMOR SUBTYPES, Female, Chromosomes, Human, Pair 9, Research Article, Adult, Breast cancer, BRCA1, BRCA2, medicine.medical_specialty, Heterozygote, SUSCEPTIBILITY LOCI, Single-nucleotide polymorphism, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Polymorphism, Single Nucleotide, OVARIAN-CANCER, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, SDG 3 - Good Health and Well-being, Internal medicine, medicine, Humans, ddc:610, GENOME-WIDE ASSOCIATION, ddc:611, Genetic Association Studies, 030304 developmental biology, Aged, Gynecology, Chromosomes, Human, Pair 12, CONSORTIUM, BRCA1 Protein - genetics, ALLELES, medicine.disease, BRCA2 Protein - genetics, Cancer and Oncology, GENETIC MODIFIERS, Ovarian cancer, Transcription Factors
Abstract: INTRODUCTION: Several common alleles have been shown to be associated with breast and/or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Recent genome-wide association studies of breast cancer have identified eight additional breast cancer susceptibility loci: rs1011970 (9p21, CDKN2A/B), rs10995190 (ZNF365), rs704010 (ZMIZ1), rs2380205 (10p15), rs614367 (11q13), rs1292011 (12q24), rs10771399 (12p11 near PTHLH) and rs865686 (9q31.2). METHODS: To evaluate whether these single nucleotide polymorphisms (SNPs) are associated with breast cancer risk for BRCA1 and BRCA2 carriers, we genotyped these SNPs in 12,599 BRCA1 and 7,132 BRCA2 mutation carriers and analysed the associations with breast cancer risk within a retrospective likelihood framework. RESULTS: Only SNP rs10771399 near PTHLH was associated with breast cancer risk for BRCA1 mutation carriers (per-allele hazard ratio (HR) = 0.87, 95% CI: 0.81 to 0.94, P-trend = 3 x 10-4). The association was restricted to mutations proven or predicted to lead to absence of protein expression (HR = 0.82, 95% CI: 0.74 to 0.90, P-trend = 3.1 x 10-5, P-difference = 0.03). Four SNPs were associated with the risk of breast cancer for BRCA2 mutation carriers: rs10995190, P-trend = 0.015; rs1011970, P-trend = 0.048; rs865686, 2df-P = 0.007; rs1292011 2df-P = 0.03. rs10771399 (PTHLH) was predominantly associated with estrogen receptor (ER)-negative breast cancer for BRCA1 mutation carriers (HR = 0.81, 95% CI: 0.74 to 0.90, P-trend = 4 x 10-5) and there was marginal evidence of association with ER-negative breast cancer for BRCA2 mutation carriers (HR = 0.78, 95% CI: 0.62 to 1.00, P-trend = 0.049). CONCLUSIONS: The present findings, in combination with previously identified modifiers of risk, will ultimately lead to more accurate risk prediction and an improved understanding of the disease etiology in BRCA1 and BRCA2 mutation carriers., published_or_final_version
Published: 2012

26. Evidence for SMAD3 as a modifier of breast cancer risk in BRCA2 mutation carriers

Author: Walker, L.C., Fredericksen, Z.S., Wang, X.S., Tarrell, R., Pankratz, V.S., Lindor, N.M., Beesley, J., Healey, S., Chen, X.Q., Fab, K.C., Stoppa-Lyonnet, D., Tirapo, C., Giraud, S., Mazoyer, S., Muller, D., Fricker, J.P., Delnatte, C., Schmutzler, R.K., Wappenschmidt, B., Engel, C., Schonbuchner, I., Deissler, H., Meindl, A., Hogervorst, F.B., Verheus, M., Hooning, M.J., Ouweland, A.M.W. van den, Nelen, M.R., Ausems, M.G.E.M., Aalfs, C.M., Asperen, C.J. van, Devilee, P., Gerrits, M.M., Waisfisz, Q., Szabo, C.I., Quad, M.S., Easton, D.F., Peock, S., Cook, M., Oliver, C.T., Frost, D., Harrington, P., Evans, D.G., Lalloo, F., Eeles, R., Izatt, L., Chu, C., Davidson, R., Eccles, D., Ong, K.R., Cook, J., Rebbeck, T., Nathanson, K.L., Domchek, S.M., Singer, C.F., Gschwantler-Kaulich, D., Dressler, A.C., Pfeiler, G., Godwin, A.K., Heikkinen, T., Nevanlinna, H., Agnarsson, B.A., Caligo, M.A., Olsson, H., Kristoffersson, U., Liljegren, A., Arver, B., Karlsson, P., Melin, B., Sinilnikova, O.M., McGuffog, L., Antoniou, A.C., Chenevix-Trench, G., Spurdle, A.B., Couch, F.J., Gemo Study Collaborators, HEBON, EMBRACE, SWE BRCA, Easton, Douglas [0000-0003-2444-3247], Antoniou, Antonis [0000-0001-9223-3116], Apollo - University of Cambridge Repository, Division of Genetics and Population Health, Queensland Institute of Medical Research, Department of Laboratory Medicine and Pathology, Mayo Clinic, Pathologie moléculaire des cancers, Institut Curie [Paris]-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), Génétique moléculaire, signalisation et cancer (GMSC), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Unité d'Oncogénétique, CLCC Paul Strauss, Centre René Gauducheau, Centre for Hereditary Breast and Ovarian Cancer, Department of Obstetrics and Gynaecology-University of Cologne, Institute for Medical Informatics, Statistics and Epidemiology [Leipzig] (IMISE), Universität Leipzig [Leipzig], Institute of Human Genetics, Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), Department of Obstetrics and Gynaecology, Universität Ulm - Ulm University [Ulm, Allemagne], Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Klinikum Rechts der Isar-Division of Tumor Genetics, Family Cancer Clinic, The Netherlands Cancer Institute, Department of Epidemiology, Netherlands Cancer Institute, Department of Medical Oncology, Erasmus University Medical Center [Rotterdam] (Erasmus MC)-Family Cancer Clinic, Department of Clinical Genetics, Department of Human Genetics, University Nijmegen Medical Centre, Department of Medical Genetics, University Medical Center [Utrecht], Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), Leiden University Medical Center (LUMC), Department of Human Genetics & Department of Pathology, Department of Genetics and Cell Biology, VU University Medical Center [Amsterdam], Strangeways Research Laboratory, University of Cambridge [UK] (CAM)-Department of Public Health and Primary Care-Centre for Cancer Genetic Epidemiology, Centre for Cancer Genetic Epidemiology [Cambridge], Department of Oncology-University of Cambridge [UK] (CAM), Genetic Medicine, St Mary's Hospital-NHS Foundation Trust-Manchester Academic Health Sciences Centre-Central Manchester University Hospitals, Oncogenetics Team, The Institute of Cancer Research-Royal Marsden NHS Foundation Trust, Clinical Genetics Department, Guy's and St Thomas NHS Foundation Trust-Guys Hospital, Yorkshire Regional Genetics Service, St. James's Hospital, Ferguson-Smith Centre for Clinical Genetics, Wessex Clinical Genetics Service, Princess Anne Hospital-Cancer Sciences Division, West Midlands Regional Genetics Service, Birmingham Women's and Children's NHS Foundation Trust, Sheffield Clinical Genetics Service, Sheffield Children's NHS Foundation Trust, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], Division of Special Gynecology, Medizinische Universität Wien = Medical University of Vienna-Department of OB/GYN, Women's Cancer Program, Fox Chase Cancer Center, Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Department of Pathology, University Hospital and University of Iceland School of Medicine, Section of Genetic Oncology, University of Pisa - Università di Pisa, Department of Oncology, Lund University Hospital, Karolinska University Hospital [Stockholm], Sahlgrenska University Hospital [Gothenburg], Department of Radiation Sciences and Oncology, Umeå University, kConFab, GEMO Study Collaborators, HEBON, ModSQuaD, EMBRACE, SWE-BRCA, Human Genetics, BMC, Ed., Julius-Maximilians-Universität Würzburg (JMU), University of Cambridge [UK] (CAM)-Department of Oncology, University of Pennsylvania-University of Pennsylvania, Medical Oncology, Clinical Genetics, Gastroenterology & Hepatology, Targeted Gynaecologic Oncology (TARGON), and Damage and Repair in Cancer Development and Cancer Treatment (DARE)
Subjects: MESH: Signal Transduction, Linkage disequilibrium, Candidate gene, endocrine system diseases, Genes, BRCA2, Gene Expression, Genome-wide association study, Gene mutation, Linkage Disequilibrium, 0302 clinical medicine, MESH: Aged, 80 and over, MESH: Risk Factors, Risk Factors, Transforming Growth Factor beta, INVESTIGATORS, skin and connective tissue diseases, POPULATION, Medicine(all), Genetics, MESH: Aged, Aged, 80 and over, 0303 health sciences, MESH: Middle Aged, MESH: Polymorphism, Single Nucleotide, MESH: Genetic Predisposition to Disease, Middle Aged, BRCA2 Protein, MESH: Linkage Disequilibrium, 030220 oncology & carcinogenesis, Female, Signal Transduction, Research Article, Adult, MESH: Mutation, MESH: Gene Expression, GENES, Single-nucleotide polymorphism, [SDV.CAN]Life Sciences [q-bio]/Cancer, Breast Neoplasms, Biology, Polymorphism, Single Nucleotide, OVARIAN-CANCER, PROPHYLACTIC OOPHORECTOMY, 03 medical and health sciences, Breast cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, SDG 3 - Good Health and Well-being, medicine, MESH: Smad3 Protein, Humans, Genetic Predisposition to Disease, COHORT, Smad3 Protein, GENOME-WIDE ASSOCIATION, MESH: Transforming Growth Factor beta, 030304 developmental biology, Genetic association, Aged, MESH: Humans, CONSORTIUM, MESH: Adult, ALLELES, medicine.disease, POLYMORPHISM, Cancer and Oncology, MESH: Genome-Wide Association Study, Mutation, MESH: Female, MESH: Breast Neoplasms, MESH: Genes, BRCA2, Genome-Wide Association Study
Abstract: Introduction: Current attempts to identify genetic modifiers of BRCA1 and BRCA2 associated risk have focused on a candidate gene approach, based on knowledge of gene functions, or the development of large genome-wide association studies. In this study, we evaluated 24 SNPs tagged to 14 candidate genes derived through a novel approach that analysed gene expression differences to prioritise candidate modifier genes for association studies.Methods: We successfully genotyped 24 SNPs in a cohort of up to 4,724 BRCA1 and 2,693 BRCA2 female mutation carriers from 15 study groups and assessed whether these variants were associated with risk of breast cancer in BRCA1 and BRCA2 mutation carriers.Results: SNPs in five of the 14 candidate genes showed evidence of association with breast cancer risk for BRCA1 or BRCA2 carriers (P Conclusions: This study provides evidence that the SMAD3 gene, which encodes a key regulatory protein in the transforming growth factor beta signalling pathway and is known to interact directly with BRCA2, may contribute to increased risk of breast cancer in BRCA2 mutation carriers. This finding suggests that genes with expression associated with BRCA1 and BRCA2 mutation status are enriched for the presence of common genetic modifiers of breast cancer risk in these populations.
Published: 2010

27. Detecting differential allelic expression using high-resolution melting curve analysis: application to the breast cancer susceptibility gene CHEK2

Author: Olga M. Sinilnikova, Florence Le Calvez-Kelm, Melissa C. Southey, Lars Petter Jordheim, Sandrine McKay-Chopin, Jocelyne Michelon, Tu Nguyen-Dumont, Sean V. Tavtigian, Fabienne Lesueur, Nathalie Forey, Section Génétique - Groupe Prédispositions génétiques au cancer, Centre International de Recherche contre le Cancer (CIRC), 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), Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL), Department of Pathology, University of Melbourne, Department of Oncological Sciences, University of Utah-Huntsman Cancer Institute, kConFab is supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC) and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. We gratefully acknowledge Arnaud Dumont for his help on developing the R script. TN-D was the recipient of a fellowship from Fondation de France and a Special Trainee Award from the International Agency for Research on Cancer. LPJ was the recipient of a fellowship from Ligue Contre le Cancer - Comité du Rhône. MCS is a National Health and Medical Research Council Senior Research Fellow and Victorian Breast cancer Research Consortium (VBCRC) Group Leader. This work was also supported by the Canadian Institutes of Health Research team grant CRN-87521-IC089832 and by the National Cancer Institute, National Institutes of Health (NIH) grant R01 CA121245., for Kathleen Cuningham Foundation Consortium for Research into Familial Aspects of Breast Cancer (kConFab), and BMC, Ed.
Subjects: Candidate gene, RNA Stability, DNA Mutational Analysis, Allelic Imbalance, medicine.disease_cause, Nucleic Acid Denaturation, MESH: Genotype, 0302 clinical medicine, Coding region, Genetics(clinical), MESH: Codon, Nonsense, MESH: DNA Mutational Analysis, skin and connective tissue diseases, Genetics (clinical), MESH: Heterozygote, Regulation of gene expression, Genetics, 0303 health sciences, Mutation, MESH: Polymorphism, Single Nucleotide, MESH: Genetic Predisposition to Disease, MESH: RNA Stability, MESH: Gene Expression Regulation, Neoplastic, Exons, Gene Expression Regulation, Neoplastic, Codon, Nonsense, 030220 oncology & carcinogenesis, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, Research Article, lcsh:Internal medicine, Heterozygote, MESH: Cell Line, Tumor, lcsh:QH426-470, Genotype, Breast Neoplasms, MESH: Nucleic Acid Denaturation, Biology, Protein Serine-Threonine Kinases, Polymorphism, Single Nucleotide, MESH: Protein-Serine-Threonine Kinases, 03 medical and health sciences, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Cell Line, Tumor, medicine, Humans, Genetic Predisposition to Disease, lcsh:RC31-1245, Gene, CHEK2, MESH: Genes, Neoplasm, Alleles, 030304 developmental biology, MESH: Humans, MESH: Alleles, MESH: Allelic Imbalance, lcsh:Genetics, Checkpoint Kinase 2, Human genome, MESH: Exons, MESH: Female, MESH: Breast Neoplasms, Genes, Neoplasm
Abstract: BackgroundThe geneCHEK2encodes a checkpoint kinase playing a key role in the DNA damage pathway. ThoughCHEK2has been identified as an intermediate breast cancer susceptibility gene, only a small proportion of high-risk families have been explained by genetic variants located in its coding region. Alteration in gene expression regulation provides a potential mechanism for generating disease susceptibility. The detection of differential allelic expression (DAE) represents a sensitive assay to direct the search for a functional sequence variant within the transcriptional regulatory elements of a candidate gene. We aimed to assess whetherCHEK2was subject to DAE in lymphoblastoid cell lines (LCLs) from high-risk breast cancer patients for whom no mutation inBRCA1orBRCA2had been identified.MethodsWe implemented an assay based on high-resolution melting (HRM) curve analysis and developed an analysis tool for DAE assessment.ResultsWe observed allelic expression imbalance in 4 of the 41 LCLs examined. All four were carriers of the truncating mutation 1100delC. We confirmed previous findings that this mutation induces non-sense mediated mRNA decay. In our series, we ruled out the possibility of a functional sequence variant located in the promoter region or in a regulatory element ofCHEK2that would lead to DAE in the transcriptional regulatory milieu of freely proliferating LCLs.ConclusionsOur results support that HRM is a sensitive and accurate method for DAE assessment. This approach would be of great interest for high-throughput mutation screening projects aiming to identify genes carrying functional regulatory polymorphisms.
Published: 2011

28. P19-23. Putative prefusion mechanism of HIV-1 Env revealed by ligand-induced quaternary alterations in o-gp140 trimers

Author: Loïc Martin, R Cheng, Dj Green, Indresh K. Srivastava, S Poon, Frank I. Lin, Li Xing, Susan W. Barnett, Cg Moscoso, Elaine Kan, Yide Sun, Department of Chemistry - The Chinese University of Hong-Kong, The Chinese University of Hong Kong [Hong Kong], Service d'Ingénierie Moléculaire pour la Santé (ex SIMOPRO) (SIMoS), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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), 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-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-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: lcsh:Immunologic diseases. Allergy, Chemokine, viruses, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Gp41, Cleavage (embryo), Bioinformatics, 03 medical and health sciences, Protein structure, Mediator, Virology, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], 030306 microbiology, Chemistry, virus diseases, Lipid bilayer fusion, Transmembrane protein, 3. Good health, Cell biology, Cytosol, Infectious Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Poster Presentation, biology.protein, lcsh:RC581-607
Abstract: Background The human immunodeficiency virus envelope spike is the key mediator of membrane fusion with the host cell and is a promising research target for vaccine development. The surface spike gp120 and the transmembrane protein gp41 result from cleavage of immature cytosolic gp160 and are expressed as trimers. Conformational rearrangement upon binding of gp120 to host CD4 receptors and chemokine coreceptors mediates membrane fusion, exposes the fusion peptide of gp41 and enables viral genome insertion.
Published: 2009

29. Testicular impairment in Primary Adrenal Insufficiency caused by Nicotinamide Nucleotide Transhydrogenase (NNT) deficiency - a case report: implication of oxidative stress and importance of fertility preservation.

Author: Ferreux L, Boumerdassi Y, Dulioust E, Bertagna X, Roucher-Boulez F, Bourdon M, Thiounn N, and Patrat C
Abstract: Introduction: Nicotinamide nucleotide transhydrogenase (NNT) gene deficiency has recently been shown to be involved in Primary Adrenal Insufficiency (PAI). NNT encodes an inner mitochondrial membrane protein that produces large amounts of NADPH. NADPH is used in several biosynthesis pathways and the oxidoreduction of free radicals by the glutathione and thioredoxin systems in mitochondria. Patients with PAI due to NNT deficiency may also exhibit extra-adrenal manifestations, usually including gonadal impairment., Case Report: We present the case of a 35-year-old patient referred to our center for primary infertility with non-obstructive azoospermia, in a context of PAI and obesity. PAI genetic exploration carried out at the age of thirty revealed NNT deficiency due to the presence of two deleterious mutations (one on each allele) in the NNT gene. Scrotal ultrasound revealed a right Testicular Adrenal Rest Tumor (TART). Intensification of glucocorticoid therapy over the course of 8 months failed to reduce the TART volume or improve sperm production and endocrine function. No spermatozoa were found after surgical exploration of both testes, and subsequent histopathological analysis revealed bilateral Sertoli cell-only syndrome. A retrospective review of the hypothalamic-pituitary-gonadic axis hormonal assessment over 20 years showed progressive impairment of testicular function, accelerated during adulthood, leading to hypergonadotropic hypogonadism and non-obstructive azoospermia when the patient reached his thirties, while the PAI remained controlled over the same period., Conclusion: This case report provides, for the first time, direct evidence of complete germ line loss in an azoospermic man with NNT deficiency. Additional data further support the hypothesis of a determinant role of oxidative cellular damage due to reactive oxygen species (ROS) imbalance in the severe gonadal impairment observed in this NNT-deficient patient. Early and regular evaluation of gonadal function should be performed in patients with PAI, especially with NNT deficiency, as soon as the patients reach puberty. Fertility preservation options should then be provided in early adulthood for these patients., (© 2023. The Author(s).)
Published: 2023
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30. National influenza surveillance systems in five European countries: a qualitative comparative framework based on WHO guidance.

Author: de Fougerolles TR, Damm O, Ansaldi F, Chironna M, Crépey P, de Lusignan S, Gray I, Guillen JM, Kassianos G, Mosnier A, de Lejarazu RO, Pariani E, Puig-Barbera J, Schelling J, Trippi F, Vanhems P, Wahle K, Watkins J, Rasuli A, Vitoux O, and Bricout H
Subjects: Europe epidemiology, France epidemiology, Humans, United Kingdom epidemiology, World Health Organization, Influenza, Human epidemiology
Abstract: Background: Influenza surveillance systems vary widely between countries and there is no framework to evaluate national surveillance systems in terms of data generation and dissemination. This study aimed to develop and test a comparative framework for European influenza surveillance., Methods: Surveillance systems were evaluated qualitatively in five European countries (France, Germany, Italy, Spain, and the United Kingdom) by a panel of influenza experts and researchers from each country. Seven surveillance sub-systems were defined: non-medically attended community surveillance, virological surveillance, community surveillance, outbreak surveillance, primary care surveillance, hospital surveillance, mortality surveillance). These covered a total of 19 comparable outcomes of increasing severity, ranging from non-medically attended cases to deaths, which were evaluated using 5 comparison criteria based on WHO guidance (granularity, timing, representativeness, sampling strategy, communication) to produce a framework to compare the five countries., Results: France and the United Kingdom showed the widest range of surveillance sub-systems, particularly for hospital surveillance, followed by Germany, Spain, and Italy. In all countries, virological, primary care and hospital surveillance were well developed, but non-medically attended events, influenza cases in the community, outbreaks in closed settings and mortality estimates were not consistently reported or published. The framework also allowed the comparison of variations in data granularity, timing, representativeness, sampling strategy, and communication between countries. For data granularity, breakdown per risk condition were available in France and Spain, but not in the United Kingdom, Germany and Italy. For data communication, there were disparities in the timeliness and accessibility of surveillance data., Conclusions: This new framework can be used to compare influenza surveillance systems qualitatively between countries to allow the identification of structural differences as well as to evaluate adherence to WHO guidance. The framework may be adapted for other infectious respiratory diseases., (© 2022. The Author(s).)
Published: 2022
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31. Whole exome sequencing in three families segregating a pediatric case of sarcoidosis.

Author: Calender A, Rollat Farnier PA, Buisson A, Pinson S, Bentaher A, Lebecque S, Corvol H, Abou Taam R, Houdouin V, Bardel C, Roy P, Devouassoux G, Cottin V, Seve P, Bernaudin JF, Lim CX, Weichhart T, Valeyre D, Pacheco Y, Clement A, and Nathan N
Subjects: Base Sequence, Child, Female, Genetic Variation, Genome-Wide Association Study, Humans, Male, Pedigree, Sarcoidosis genetics, Exome Sequencing
Abstract: Background: Sarcoidosis (OMIM 181000) is a multi-systemic granulomatous disorder of unknown origin. Despite multiple genome-wide association (GWAS) studies, no major pathogenic pathways have been identified to date. To find out relevant sarcoidosis predisposing genes, we searched for de novo and recessive mutations in 3 young probands with sarcoidosis and their healthy parents using a whole-exome sequencing (WES) methodology., Methods: From the SARCFAM project based on a national network collecting familial cases of sarcoidosis, we selected three families (trios) in which a child, despite healthy parents, develop the disease before age 15 yr. Each trio was genotyped by WES (Illumina HiSEQ 2500) and we selected the gene variants segregating as 1) new mutations only occurring in affected children and 2) as recessive traits transmitted from each parents. The identified coding variants were compared between the three families. Allelic frequencies and in silico functional results were analyzed using ExAC, SIFT and Polyphenv2 databases. The clinical and genetic studies were registered by the ClinicalTrials.gov - Protocol Registration and Results System (PRS) ( https://clinicaltrials.gov ) receipt under the reference NCT02829853 and has been approved by the ethical committee (CPP LYON SUD EST - 2 - REF IRB 00009118 - September 21, 2016)., Results: We identified 37 genes sharing coding variants occurring either as recessive mutations in at least 2 trios or de novo mutations in one of the three affected children. The genes were classified according to their potential roles in immunity related pathways: 9 to autophagy and intracellular trafficking, 6 to G-proteins regulation, 4 to T-cell activation, 4 to cell cycle and immune synapse, 2 to innate immunity. Ten of the 37 genes were studied in a bibliographic way to evaluate the functional link with sarcoidosis., Conclusions: Whole exome analysis of case-parent trios is useful for the identification of genes predisposing to complex genetic diseases as sarcoidosis. Our data identified 37 genes that could be putatively linked to a pediatric form of sarcoidosis in three trios. Our in-depth focus on 10 of these 37 genes may suggest that the formation of the characteristic lesion in sarcoidosis, granuloma, results from combined deficits in autophagy and intracellular trafficking (ex: Sec16A, AP5B1 and RREB1), G-proteins regulation (ex: OBSCN, CTTND2 and DNAH11), T-cell activation (ex: IDO2, IGSF3), mitosis and/or immune synapse (ex: SPICE1 and KNL1). The significance of these findings needs to be confirmed by functional tests on selected gene variants.
Published: 2018
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31 results on '"Hospices Civils de Lyon (HCL)"'

1. Proposition of a corrected measure of the Lawton instrumental activities of daily living score

2. Can levosimendan reduce ECMO weaning failure in cardiogenic shock? A cohort study with propensity score analysis

3. Study protocol of the HYPER-LIV01 trial: a multicenter phase II, prospective and randomized study comparing simultaneous portal and hepatic vein embolization to portal vein embolization for hypertrophy of the future liver remnant before major hepatectomy for colo-rectal liver metastases

4. Anatomic risk factor for meniscal lesion in association with ACL rupture

5. Cross sectional study on prevalence of sickle cell alleles S and C among patients with mild malaria in Ivory Coast

6. High-flow nasal oxygen vs. standard oxygen therapy in immunocompromised patients with acute respiratory failure: study protocol for a randomized controlled trial

7. Chronic Lyme borreliosis associated with minimal change glomerular disease: a case report

8. Intradermal injection of human adipose-derived stem cells accelerates skin wound healing in nude mice

9. Targeted screening for third-generation cephalosporin-resistant Enterobacteriaceae carriage among patients admitted to intensive care units: a quasi-experimental study

10. In vivo free-breathing DTI & IVIM of the whole human heart using a real-time slice-followed SE-EPI navigator-based sequence: a reproducibility study in healthy volunteers

11. The prediction of hospital length of stay using unstructured data

12. Lower ribavirin biodisponibility in patients with HIV-HCV coinfection in comparison with HCV monoinfected patients

13. Potential of pre-contrast T1 mapping as a marker of interstitial fibrosis in severe aortic stenosis

14. Regulation of chemokine and chemokine receptor expression by PPARG in adipocytes and macrophages

15. Severe metabolic or mixed acidemia on intensive care unit admission: incidence, prognosis and administration of buffer therapy. a prospective, multiple-center study

16. Prognostic value of the expression of C-Chemokine Receptor 6 and 7 and their ligands in non-metastatic breast cancer

17. Impact of a multifaceted program to prevent postoperative delirium in the elderly: the CONFUCIUS stepped wedge protocol

18. Determination of the myocardial area at risk after reperfused acute myocardial infarction with different imaging techniques: cardiac magnetic resonance imaging, multidetector computed tomography and histopathological validation

19. Strategies of initiation and streamlining of antibiotic therapy in 41 French intensive care units

20. Hydroxychloroquine levels in patients with systemic lupus erythematosus: whole blood is preferable but serum levels also detect non-adherence

21. Treatment of voluminous and complicated superficial slow-flow vascular malformations with sirolimus (PERFORMUS): protocol for a multicenter phase 2 trial with a randomized observational-phase design

22. Prevalence, risk factors for infection and subtype distribution of the intestinal parasite Blastocystis sp. from a large-scale multi-center study in France

23. Assessment of the contribution of morbidity and mortality conferences to quality and safety improvement: a survey of participants’ perceptions

24. Exploring the link between MORF4L1 and risk of breast cancer

25. Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers

26. Evidence for SMAD3 as a modifier of breast cancer risk in BRCA2 mutation carriers

27. Detecting differential allelic expression using high-resolution melting curve analysis: application to the breast cancer susceptibility gene CHEK2

28. P19-23. Putative prefusion mechanism of HIV-1 Env revealed by ligand-induced quaternary alterations in o-gp140 trimers

29. Testicular impairment in Primary Adrenal Insufficiency caused by Nicotinamide Nucleotide Transhydrogenase (NNT) deficiency - a case report: implication of oxidative stress and importance of fertility preservation.

30. National influenza surveillance systems in five European countries: a qualitative comparative framework based on WHO guidance.

31. Whole exome sequencing in three families segregating a pediatric case of sarcoidosis.

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