Author: "Hospices Civils de Lyon (HCL)" / Topic: medicine.disease - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Hospices Civils de Lyon (HCL)"' showing total 4,100 results

Start Over Author "Hospices Civils de Lyon (HCL)" Topic medicine.disease

4,100 results on '"Hospices Civils de Lyon (HCL)"'

1. Regression of Q waves and clinical outcomes following primary PCI in anterior STEMI

Author: Mathieu Schaaf, Inesse Boussaha, Claire Jossan, Thomas Bochaton, Sophie Pichot-Lamoureux, Denis Angoulvant, Nathan Mewton, Marc J. Claeys, Michel Ovize, Grégoire Rangé, Yuni de Framond, Olivier Dubreuil, David Garcia Dorado, Gilles Rioufol, CHU Tenon [APHP], 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 Cardiology, Hospices Civils de Lyon (HCL), Johns Hopkins University School of Medicine [Baltimore], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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: medicine.medical_specialty, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Population, Myocardial Infarction, Left ventricle remodeling, Stunned myocardium, 030204 cardiovascular system & hematology, Lower risk, Infarct size, QT interval, Ventricular Function, Left, Electrocardiography, 03 medical and health sciences, Percutaneous Coronary Intervention, 0302 clinical medicine, Internal medicine, medicine, Humans, cardiovascular diseases, 030212 general & internal medicine, education, Creatine Kinase, Heart Failure, education.field_of_study, Ejection fraction, biology, Anterior ST-elevation myocardial infarction, business.industry, Percutaneous coronary intervention, Stroke Volume, Q wave regression, medicine.disease, 3. Good health, Heart failure, Conventional PCI, biology.protein, Cardiology, ST Elevation Myocardial Infarction, Creatine kinase, Human medicine, Cardiology and Cardiovascular Medicine, business
Abstract: Background: Pathological Q waves are correlated with infarct size, and Q-wave regression is associated with left ventricular ejection fraction improvement. There are limited data regarding the association of Q-wave regression and clinical outcomes. Our main objective was to assess the association of pathological Q wave evolution after re-perfusion with clinical outcomes after anterior STEMI.Methods: Standard 12-lead electrocardiograms (ECGs) were recorded in 780 anterior STEMI patients treated with primary percutaneous coronary intervention (PCI) from the CIRCUS trial. ECGs were recorded before and 90 min following PCI, as well as at hospitalization discharge and 12 months of follow-up. The number of classic ECG criteria Q waves was scored for each ECG. Patients were classified in the Q wave regression group if they had re-gression of at least one Q wave between the post-PCI, the discharge and/or one year ECGs. Patients were classified in the Q wave persistent group if they had the same number or greater between the post-PCI, the discharge and/ or 1 and one year ECGs. All-cause death and heart failure events were assessed for all patients at one year.Results: There were 323(43%) patients with persistent Q waves (PQ group), 378(49%) patients with Q wave re-gression (RQ group) and 60(8%) patients with non-Q wave MI (NQ group). Infarct size as measured by the peak creatine kinase was significantly greater in the PQ group compared to the RQ and NQ groups (4633 +/- 2784 IU/l vs. 3814 +/- 2595 IU/l vs. 1733 +/- 1583 IU/l respectively, p b 0.0001). At one year, there were 22 deaths (7%) in the PQ-group, 15 (4%) in the RQ-group and none in the NQ-group (p = 0.04). There was a 4-fold increase in the risk of death or heart failure in the PQ compared to the NQ group (HR 4.7 [1.1; 19.3]; p = 0.03), but there was no significant difference between NQ and RQ groups (HR 3.3 [0.8; 13.8]; p = 0.09).Conclusion: Ina population of anterior STEMI patients, persistent Q waves defined according to the classic ECG criteria after reperfusion was associated with a 4-fold increase in the risk of heart failure or death compared to non-Q-wave MI, while Q-wave regression was associated with significantly lower risk of events.(c) 2019 Elsevier Inc. All rights reserved.
Published: 2022

2. Funding kidney research as a public health priority

Author: Ziad A. Massy, Dimitrios S. Goumenos, Annette Bruchfeld, Ivan Rychlik, Carsten A. Wagner, Hans-Joachim Anders, Tom Oostrom, Carmine Zoccali, Giovambattista Capasso, Ron T. Gansevoort, María José Soler, Kate Stevens, Denis Fouque, Peter J. Blankestijn, Goce Spasovski, Danilo Fliser, Friedo W. Dekker, Kitty J Jager, Mario Cozzolino, Christoph Wanner, Raymond Vanholder, University of Zurich, Universita Mediterranea of Reggio Calabria [Reggio Calabria], Ghent University Hospital, European Kidney Health Alliance (EKHA), University hospital of Zurich [Zurich], Klinikum der Universität [München], University Medical Center [Utrecht], Karolinska University Hospital [Stockholm], University of the Study of Campania Luigi Vanvitelli, University of Milan, Leiden University Medical Center (LUMC), Saarland University [Saarbrücken], Université de la Sarre, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), University Medical Center Groningen [Groningen] (UMCG), General University Hospital of Patras, University of Amsterdam [Amsterdam] (UvA), Épidémiologie et recherches translationnelles sur les maladies rénales et cardiovasculaires (EPREC) (U1018 (Équipe 5)), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Dutch Kidney Foundation [Bussum, The Netherlands] (DKF), Charles University [Prague] (CU), Vall d’Hebron Research Institute (VHIR), Queen Elizabeth University Hospital (Glasgow), Ss. Cyril and Methodius University in Skopje, University of Würzburg, CarMeN, laboratoire, Università degli Studi di Milano = University of Milan (UNIMI), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Ss. Cyril and Methodius University in Skopje (UKIM)
Subjects: medicine.medical_specialty, kidney, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, 610 Medicine & health, 030204 cardiovascular system & hematology, 10052 Institute of Physiology, 03 medical and health sciences, 0302 clinical medicine, Renal Dialysis, medicine, CKD, Humans, Transplantation, research, Health Priorities, business.industry, Public health, funding, Public relations, medicine.disease, Medical research, 3. Good health, [SDV] Life Sciences [q-bio], Europe, Seed money, Alliance, Framing (social sciences), scientific societies, Nephrology, 570 Life sciences, biology, Public Health, business, Working group, Social responsibility, Kidney disease
Abstract: Medical societies have a social responsibility to disseminate knowledge and inform health authorities on threats to public health posed by various diseases. Advocacy for health protection programmes and for medical research funding is now embedded into the missions of most scientific societies. To promote kidney research funding in Europe, the European Renal Association – European Dialysis and Transplant Association (ERA-EDTA), rather than acting as an individual society advocating for the fight against kidney disease, has actively helped to create an alliance of national associations centred on kidney diseases, the European Kidney Health Alliance (EKHA), and joined the Biomedical Alliance (BMA). The ERA-EDTA is fully committed to supporting its working groups (WGs) and consortia of its members to allow them to produce valuable kidney research. The framing and formalization of projects, and the regulatory issues related to submission to the European Commission, are complex. To help WGs to gain expert advice from agencies with specific know-how, the ERA-EDTA has adopted a competitive approach. The best research projects proposed by WGs and consortia of other European investigators will receive seed funding to cover the costs of consultancy by expert agencies. Via its broader platforms, the EKHA and the BMA, the ERA-EDTA will strive towards broader recognition of kidney disease and related clusters of non-communicable diseases, by European and national agencies, as major threats to the qualities of life of their populations and their economies.
Published: 2022

3. Cyclophosphamide added to glucocorticoids in acute exacerbation of idiopathic pulmonary fibrosis (EXAFIP): a randomised, double-blind, placebo-controlled, phase 3 trial

Author: Abdellatif Tazi, Aurélie Le Borgne-Krams, Marine Cachanado, Tabassome Simon, Sylvain Marchand-Adam, Morgane Didier, Lidwine Wemeau-Stervinou, Sandrine Hirschi, Frédéric Rivière, Arnaud Bourdin, François Lebargy, Stéphane Dominique, Aude Gibelin, Alexandre Chabrol, Tristan Dégot, Jacques Cadranel, Martine Reynaud-Gaubert, Marie-Pierre Debray, Sylvie Leroy, Frédéric Gagnadoux, Emmanuel Bergot, François-Xavier Blanc, Alexandra Rousseau, Raphael Borie, Pierre Yves Brillet, Guillaume Beltramo, Mallorie Kerjouan, Hilario Nunes, Olivia Freynet, Julie Traclet, Bruno Crestani, Anne-Sophie Gamez, Grégoire Prévot, Jean Pastré, Dominique Israel-Biet, Marie-Christine Dombret, Laurent Plantier, Cécile Chenivesse, Laurence Berard, Ana Nieves, Emmanuel Gomez, Dominique Valeyre, Stéphane Jouneau, Anne Gondouin, Elodie Blanchard, C. Launois, Nathalie Bautin, Jean-Marc Naccache, Vincent Cottin, Antoine Parrot, Philippe Bonniaud, Centre de référence maladies rares des maladies pulmonaires rares de l’adulte (CHU Dijon) (CRMR des maladies pulmonaires rares de l’adulte), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Sorbonne Université (SU), Centre hospitalier Saint-Joseph [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Foch [Suresnes], CHU Pontchaillou [Rennes], École des Hautes Études en Santé Publique [EHESP] (EHESP), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hôpital Avicenne [AP-HP], Laboratoire d'Excellence INFLAMEX [Paris], Université Sorbonne Paris Cité (USPC), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP - Hôpital Bichat - Claude Bernard [Paris], CHU Saint-Antoine [AP-HP], Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre régional de pharmacovigilance de Marseille Provence Corse [CHU de Marseille] (CRPV-Marseille), Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille, CHU Dijon, Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), 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), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Les Hôpitaux Universitaires de Strasbourg (HUS), Nouvel Hôpital Civil de Strasbourg, Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Lille, Hôpital Albert Calmette, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Référence des Maladies Pulmonaires Rares [Hôpital Louis Pradel - HCL], Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL), Université de Lyon, CIC CHU Lyon (inserm), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nice (CHU Nice), Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital d'instruction des Armées Percy, Service de Santé des Armées, Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital JeanMinjoz, CHU Bordeaux [Bordeaux], Hôpital Haut-Lévêque [CHU Bordeaux], unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Rouen, Normandie Université (NU), CHU Tenon [AP-HP], Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université Paris Cité (UPCité), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), CHU Montpellier, Université de Lille, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), 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), Roche, Ministere de la Sante et des Solidarites, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), CHU Marseille-Assistance Publique-Hôpitaux de Marseille (AP-HM), Hôpital Larrey [Toulouse], CHU Toulouse [Toulouse], Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Université de Paris (UP), 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), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, education.field_of_study, Exacerbation, Cyclophosphamide, business.industry, [SDV]Life Sciences [q-bio], Population, medicine.disease, Placebo, 3. Good health, 03 medical and health sciences, Idiopathic pulmonary fibrosis, 0302 clinical medicine, 030228 respiratory system, Methylprednisolone, Internal medicine, Clinical endpoint, Medicine, 030212 general & internal medicine, business, education, Adverse effect, ComputingMilieux_MISCELLANEOUS, medicine.drug
Abstract: Summary Background The use of cyclophosphamide in patients with acute exacerbation of idiopathic pulmonary fibrosis (IPF) is unknown. Our study was designed to evaluate the efficacy and safety of four cyclophosphamide pulses in addition to high-dose methylprednisolone in this population. Methods In this double-blind, placebo-controlled trial done in 35 departments across 31 hospitals in France, adult patients (≥18 years) with acute exacerbation of IPF and those with suspected acute exacerbation of IPF were randomly assigned in a 1:1 ratio using a web-based system to receive either intravenous pulses of cyclophosphamide (600 mg/m2) plus uromitexan as haemorrhagic cystitis prophylaxis (200 mg/m2) at the time of cyclophosphamide administration and then again, 4 h later, or placebo at days 0, 15, 30, and 60. Random assignment was stratified according to the severity of IPF and was block-balanced with variable block sizes of four or six patients. Patients receiving mechanical ventilation, with active infection, with active cancer, or who were registered on the lung transplant waiting list were excluded. All patients received standardised high-dose glucocorticoids. The investigators, patients, and the sponsor were masked to the treatment assignments. The primary endpoint was 3-month all-cause mortality, analysed by a χ2 test adhering to an intention-to-treat principle. The trial is now complete and registered with ClinicalTrials.gov , NCT02460588 . Findings Between Jan 22, 2016, and July 19, 2018, 183 patients were assessed for eligibility, of whom 120 patients were randomly assigned and 119 patients (62 [52%] with severe IPF) received at least one dose of cyclophosphamide (n=60) or placebo (n=59), all of whom were included in the intention-to-treat analysis. The 3-month all-cause mortality was 45% (27/60) in patients given cyclophosphamide compared with 31% (18/59) in the placebo group (difference 14·5% [95% CI −3·1 to 31·6]; p=0·10). Similar results were found after adjustment by IPF severity (odds ratio [OR] 1·89 [95% CI 0·89–4·04]). The risk of death at 3 months, independent of the treatment received, was higher with severe than non-severe IPF (OR 2·62 [1·12–6·12]) and was lower with the use of antifibrotic therapy (OR 0·33 [0·13–0·82]). Adverse events were similar between groups by 6 months (25 [42%] in the cyclophosphamide group vs 30 [51%] in the placebo group) and their proportion, including infections, did not differ. Overall infection was the main adverse event and occurred in 20 (33%) of 60 patients in the cyclophosphamide group versus 21 (36%) of 59 patients in the placebo group. Interpretation In patients with acute exacerbation of IPF, adding intravenous cyclophosphamide pulses to glucocorticoids increased 3-month mortality. These findings provide evidence against the use of intravenous cyclophosphamide in such patients. Funding Programme Hospitalier de Recherche Clinique of the French Ministry of Health (PHRC 2014–502), Roche Pharmaceuticals.
Published: 2022

4. Glial Fibrillary Acidic Protein Autoimmunity

Author: Daniela Molinier-Tiganas, Jonathan Biberon, Quentin Bodard, Véronique Rogemond, Anne Ruiz, Bastien Bouldoires, Celine Derollez, Philippe Diraison, Daniela Andriuta, Alberto Vogrig, Amelie Leblanc, Thomas De Broucker, Aditya Ambati, Philippe Kerschen, Géraldine Picard, Thierry Tchoumi, Eve Chanson, Anne-Laure Kaminsky, Irina Grigorashvili-Coin, Clementine Fort, Fanny Duval, Roxana Genet, Jérôme Honnorat, Kumaran Deiva, Sergio Muñiz-Castrillo, Mathilde Goudot, Bastien Joubert, François Sellal, Gabriel Mirebeau, Anais Dutray, Marion Philbert, Guillaume Rieul, Véronique Bourg, Erwan Morvan, Jonathan Ciron, Adrien Bigot, Romain Marignier, Roxana Ameli, Lucie Hopes, Jean Louis Devoize, Nahema Issa, Mickael Bonnan, Elena-Camelia Rusu, Laurent Kremer, Florence Rulquin, Alice Gravier Dumonceau, Marie Benaiteau, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (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), Département de Neuroradiologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL), Institut NeuroMyoGène (INMG), 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 du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Référence Maladie Rare 'Syndromes neurologiques Paranéoplasiques', Hospices Civils de Lyon (HCL)-Hopital Neurologique, CHU Toulouse [Toulouse], Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de neurologie [Le Kremlin Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Excitabilité nerveuse et thérapeutique (ENT), Hôpital Henri Mondor-EA 4391, Service de Physiologie Explorations Fonctionnelles-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpitaux Civils de Colmar, Centre Psychothérapique de Nancy [Laxou] (CPN), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Groupe hospitalier Pellegrin, CHU Bordeaux [Bordeaux], Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Saint Jean de Perpignan, Centre Hospitalier d'Angoulême (CH Angoulême), Université des Antilles - UFR des sciences médicales Hyacinthe Bastaraud (UA UFR SM), Université des Antilles (UA), CHU Clermont-Ferrand, Service de Neurologie [Brest], Hôpital d'Instruction des Armées 'Clermont-Tonnerre' (HIA), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Service de neurologie [Amiens], CHU Amiens-Picardie, Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Hôpital Pasteur [Nice] (CHU), CHU de Saint-Brieuc, CHU Pau, 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), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Strasbourg, Université Grenoble Alpes (UGA), and ANR-18-RHUS-0012,BETPSY,Biomarkers in autoimmune EncephaliTis and Paraneoplastic neurological SYndromes(2018)
Subjects: Adult, Male, Pathology, medicine.medical_specialty, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Myelitis, Autoimmunity, Autoimmune Diseases, Cohort Studies, Autoimmune Diseases of the Nervous System, Cerebrospinal fluid, Glial Fibrillary Acidic Protein, medicine, Humans, Child, Autoantibodies, Retrospective Studies, biology, Glial fibrillary acidic protein, business.industry, Autoantibody, Meningoencephalitis, medicine.disease, Hyperintensity, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Immunohistochemistry, Neurology (clinical), Antibody, business
Abstract: Background and ObjectivesTo report the clinical, biological, and imaging features and clinical course of a French cohort of patients with glial fibrillary acidic protein (GFAP) autoantibodies.MethodsWe retrospectively included all patients who tested positive for GFAP antibodies in the CSF by immunohistochemistry and confirmed by cell-based assay using cells expressing human GFAPα since 2017 from 2 French referral centers.ResultsWe identified 46 patients with GFAP antibodies. Median age at onset was 43 years, and 65% were men. Infectious prodromal symptoms were found in 82%. Other autoimmune diseases were found in 22% of patients, and coexisting neural autoantibodies in 11%. Tumors were present in 24%, and T-cell dysfunction in 23%. The most frequent presentation was subacute meningoencephalitis (85%), with cerebellar dysfunction in 57% of cases. Other clinical presentations included myelitis (30%) and visual (35%) and peripheral nervous system involvement (24%). MRI showed perivascular radial enhancement in 32%, periventricular T2 hyperintensity in 41%, brainstem involvement in 31%, leptomeningeal enhancement in 26%, and reversible splenial lesions in 4 cases. A total of 33 of 40 patients had a monophasic course, associated with a good outcome at last follow-up (Rankin Score ≤2: 89%), despite a severe clinical presentation. Adult and pediatric features are similar. Thirty-two patients were treated with immunotherapy. A total of 11/22 patients showed negative conversion of GFAP antibodies.DiscussionGFAP autoimmunity is mainly associated with acute/subacute meningoencephalomyelitis with prodromal symptoms, for which tumors and T-cell dysfunction are frequent triggers. The majority of patients followed a monophasic course with a good outcome.
Published: 2021

5. Ten-year outcomes of islet transplantation in patients with type 1 diabetes: Data from the Swiss-French GRAGIL network

Author: Lablanche, Sandrine, Borot, Sophie, Wojtusciszyn, Anne, Skaare, Kristina, Penfornis, Alfred, Malvezzi, Paolo, Badet, Lionel, Thivolet, Charles, Morelon, Emmanuel, Buron, Fanny, Renard, Eric, Tauveron, Igor, Villard, Oriane, Munch, Marion, Sommacal, Salomé, Clouaire, Léa, Jacquet, Morgane, Gonsaud, Laura, Camillo-Brault, Coralie, Colin, Cyrille, Bosson, Jean-Luc, Bosco, Domenico, Berney, Thierry, Kessler, Laurence, Benhamou, Pierre-Yves, GRAGIL Network, Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), CHU Grenoble, Université Grenoble Alpes (UGA), Pôle DigiDune, Hôpital JeanMinjoz, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire [Grenoble] (CHU), Modélisation et Évaluation des données complexes en Santé Publique (TIMC-MESP), Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC ), 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 (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-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 (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Centre Hospitalier Sud Francilien, CH Evry-Corbeil, Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Clermont-Ferrand, Université Clermont Auvergne (UCA), Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Nanomédecine Régénérative (NanoRegMed), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pôle Médecine Interne, Rhumatologie, Nutrition, Endocrinologie, Diabétologie (CHU de Strasbourg) (M.I.R.N.E.D), Les Hôpitaux Universitaires de Strasbourg (HUS), Université de Strasbourg (UNISTRA), Pôle de Santé Publique [Lyon], Geneva University Hospitals and Geneva University, and CarMeN, laboratoire
Subjects: Blood Glucose, medicine.medical_specialty, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Islets of Langerhans Transplantation, 030209 endocrinology & metabolism, 030230 surgery, clinical research/practice, Gastroenterology, Islets of Langerhans, 03 medical and health sciences, 0302 clinical medicine, Endocrinology/diabetology, Internal medicine, medicine, Humans, Immunology and Allergy, Pharmacology (medical), In patient, type 1 [Diabetes], Retrospective Studies, Glycemic, Transplantation, Kidney, Type 1 diabetes, geography, geography.geographical_feature_category, ddc:617, business.industry, Insulin, medicine.disease, Islet, 3. Good health, [SDV] Life Sciences [q-bio], Diabetes Mellitus, Type 1, Treatment Outcome, medicine.anatomical_structure, Metabolic control analysis, diabetes: type 1, Clinical research/practice, endocrinology/diabetology, islets of Langerhans, business, Switzerland
Abstract: International audience; To describe the 10-year outcomes of islet transplantation within the Swiss-French GRAGIL Network, in patients with type 1 diabetes experiencing high glucose variability associated with severe hypoglycemia and/or with functional kidney graft. We conducted a retrospective analysis of all subjects transplanted in the GRAGIL-1c and GARGIL-2 islet transplantation trials and analyzed components of metabolic control, graft function and safety outcomes over the 10-year period of follow-up. Forty-four patients were included between September 2003 and April 2010. Thirty-one patients completed a ten-year follow-up. Ten years after islet transplantation, median HbA1c was 7.2% [6.2-8.0] (55 mmol/mol [44-64]) vs 8.0% [7.1-9.1] (64 mmol/mol [54-76]) before transplantation (p\textless0.001). 17/23 (73.9%) recipients were free of severe hypoglycemia, 1/21 patient (4.8%) was insulin-independent and median C-peptide was 0.6 ng/ml [0.2-1.2]. Insulin requirements (UI/kg/day) were 0.3 [0.1-0.5] vs 0.5 [0.4-0.6] before transplantation (p\textless0.001). Median [IQR] β-score was 1 [0-4] (p\textless0.05 when comparing with pre-transplantation values) and 51.9% recipients had a functional islet graft at 10 years. With a 10-year follow up in a multicentric network, islet transplantation provided sustained improvement of glycemic control and was efficient to prevent severe hypoglycemia in almost 75% of the recipients.
Published: 2021

6. Cost-Effectiveness of Magnetic Resonance Imaging-Guided Thrombolysis for Patients With Stroke With Unknown Time of Onset

Author: Alexander Konnopka, Louisa-Kristin Muntendorf, Jochen B. Fiebach, Norbert Nighoghossian, Keith W. Muir, Matthias Endres, Hans-Helmut König, Florent Boutitie, Vincent Thijs, Claus Z Simonsen, Götz Thomalla, Salvador Pedraza, Christian Gerloff, Robin Lemmens, Martin Ebinger, CarMeN, laboratoire, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Hospices Civils de Lyon (HCL), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Klinik für Neurologie, Westfälische Wilhelms-Universität Münster = University of Münster (WWU), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, 10785 Berlin, Germany, Austin Health, University of Melbourne, The Florey Institute of Neuroscience and Mental Health, University Hospitals Leuven [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University of Glasgow, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta - Girona Biomedical Research Institute (IDIBGI), and Aarhus University Hospital
Subjects: thrombolysis, medicine.medical_specialty, Cost effectiveness, [SDV]Life Sciences [q-bio], Cost-Benefit Analysis, medicine.medical_treatment, Placebo, law.invention, methods [Magnetic Resonance Imaging], Randomized controlled trial, Modified Rankin Scale, law, economics [Thrombolytic Therapy], Acute care, economics [Magnetic Resonance Imaging], medicine, magnetic resonance imaging, Humans, methods [Cost-Benefit Analysis], Thrombolytic Therapy, ddc:610, cost-effectiveness, Stroke, quality-adjusted life-year, tissue-type plasminogen activator, health care economics and organizations, business.industry, Health Policy, Public Health, Environmental and Occupational Health, methods [Thrombolytic Therapy], Thrombolysis, medicine.disease, Magnetic Resonance Imaging, Markov Chains, Quality-adjusted life year, [SDV] Life Sciences [q-bio], Surgery, Computer-Assisted, Emergency medicine, Quality-Adjusted Life Years, business
Abstract: International audience; OBJECTIVES: Patients waking up with stroke symptoms are often excluded from intravenous thrombolysis with alteplase (IV-tpa). The WAKE-UP trial, a European multicenter randomized controlled trial, proved the clinical effectiveness of magnetic resonance imaging-guided IV-tpa for these patients. This analysis aimed to assess the cost-effectiveness of the intervention compared to placebo. METHODS: A Markov model was designed to analyze the cost-effectiveness over a 25-year time horizon. The model consisted of an inpatient acute care phase and a rest-of-life phase. Health states were defined by the modified Rankin Scale (mRS). Initial transition probabilities to mRS scores were based on WAKE-UP data and health state utilities on literature search. Costs were based on data from the University Medical Center Hamburg-Eppendorf, literature, and expert opinion. Incremental costs and effects over the patients' lifetime were estimated. The analysis was conducted from a formal German healthcare perspective. Univariate and probabilistic sensitivity analyses were performed. RESULTS: Treatment with IV-tpa resulted in cost savings of €51 009 and 1.30 incremental gains in quality-adjusted life-years at a 5% discount rate. Univariate sensitivity analysis revealed incremental cost-effectiveness ratio being sensitive to the relative risk of favorable outcome on mRS for placebo patients after stroke, the costs of long-term care for patients with mRS 4, and patient age at initial stroke event. In all cases, IV-tpa remained cost-effective. Probabilistic sensitivity analysis proved IV-tpa cost-effective in \textgreater95% of the simulations results. CONCLUSIONS: Magnetic resonance imaging-guided IV-tpa compared to placebo is cost-effective in patients with ischemic stroke with unknown time of onset.
Published: 2021

7. Nintedanib in idiopathic and secondary pleuroparenchymal fibroelastosis

Author: Lara Chalabreysse, Salim Si-Mohamed, Julie Traclet, François Philit, Françoise Thivolet-Béjui, Ségolène Turquier, Philippe Bonniaud, Kais Ahmad, Mouhamad Nasser, Vincent Cottin, National Reference Center for Rare Pulmonary Diseases, Hospices Civils de Lyon (HCL), 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), Hospices Civils de Lyon, Hôpital Louis Pradel, Lyon, France., Croix-Rousse Hospital, Hospices civils de Lyon, Université Bourgogne Franche-Comté [COMUE] (UBFC), Infections Virales et Pathologie Comparée - UMR 754 (IVPC), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ROSSI, Sabine, Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: medicine.medical_specialty, Indoles, Nintedanib, 030204 cardiovascular system & hematology, Controlled studies, Gastroenterology, Pulmonary function testing, Pulmonary fibrosis, 03 medical and health sciences, chemistry.chemical_compound, FEV1/FVC ratio, 0302 clinical medicine, Pharmacotherapy, Internal medicine, CT volumetry, medicine, Humans, Pharmacology (medical), Lung volumes, Prospective Studies, Genetics (clinical), Retrospective Studies, Pulmonary function tests, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Progression, business.industry, Research, Pleuroparenchymal fibroelastosis, General Medicine, medicine.disease, Prognosis, Respiratory Function Tests, 3. Good health, 030228 respiratory system, chemistry, Tolerability, Medicine, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background Pleuroparenchymal fibroelastosis (PPFE) has a variable disease course with dismal prognosis in the majority of patients with no validated drug therapy. This study is to evaluate the effect of nintedanib in patients with idiopathic and secondary PPFE. Patients admitted to a tertiary care center (2010–2019) were included into this retrospective analysis if they had a multidisciplinary diagnosis of PPFE, had been followed-up for 3 months or more, and had lung function tests and chest CTs available for review. Changes in pulmonary function tests were assessed using non-parametric tests and linear mixed effect model. Lung volumes were measured with lobar segmentation using chest CT. Results Out of 21 patients with PPFE, nine had received nintedanib, six had received another treatment and another six patients were monitored without drug therapy. Annual FVC (% of predicted) relative decline was − 13.6 ± 13.4%/year before nintedanib and − 1.6 ± 6.02%/year during nintedanib treatment (p = 0.014), whereas no significant change in FVC% relative decline was found in patients receiving another treatment (− 13.25 ± 34 before vs − 16.61 ± 36.2%/year during treatment; p = 0.343). Using linear mixed effect model, the slope in FVC was − 0.97%/month (95% CI: − 1.42; − 0.52) before treatment and − 0.50%/month (95% CI: − 0.88; 0.13) on nintedanib, with a difference between groups of + 0.47%/month (95% CI: 0.16; 0.78), p = 0.004. The decline in the upper lung volumes measured by CT was − 233 mL/year ± 387 mL/year before nintedanib and − 149 mL/year ± 173 mL/year on nintedanib (p = 0.327). Nintedanib tolerability was unremarkable. Conclusion In patients with PPFE, nintedanib treatment might be associated with slower decline in lung function, paving the way for prospective, controlled studies.
Published: 2021

8. Haemodynamic parameters associated with renal function prior to and following heart transplantation

Author: Nathan Mewton, Elisabeth Hugon-Vallet, Juliette Bourdin, Matteo Pozzi, Nicolas Girerd, Guillaume Baudry, Laurent Sebbag, Patrick Rossignol, Antoine Jobbe Duval, Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), The Nancy team is supported by the RHU Fight-HF, a public grant overseen by the French National Research Agency(ANR) as part of the second ‘Investissements d’Avenir’ programme (reference: ANR-15-RHUS-0004), the FrenchPIA project ‘Lorraine Université d’Excellence’ (reference: ANR-15-IDEX-04-LUE), the ANR FOCUS-MR (reference: ANR-15-CE14-0032-01), the ERA-CVD EXPERT (reference: ANR-16- ECVD-0002-02), the Contrat de Plan Etat Lorraine IT2MP, and FEDER Lorraine., ANR-15-RHUS-0004,FIGHT-HF,Combattre l'insuffisance cardiaque(2015), ANR-15-IDEX-0004,LUE,Isite LUE(2015), ANR-15-CE14-0032,MR-focus,Régulation, Diagnostique et Thérapeutique ciblée du récepteur minéralocorticoïde dans le remodelage cardiaque(2015), ANR-16-ECVD-0002,EXPERT,Exploring new pathways in age-related heart diseases(2016), European Project, BOZEC, Erwan, Combattre l'insuffisance cardiaque - - FIGHT-HF2015 - ANR-15-RHUS-0004 - RHUS - VALID, ISITE - Isite LUE - - LUE2015 - ANR-15-IDEX-0004 - IDEX - VALID, Régulation, Diagnostique et Thérapeutique ciblée du récepteur minéralocorticoïde dans le remodelage cardiaque - - MR-focus2015 - ANR-15-CE14-0032 - AAPG2015 - VALID, Exploring new pathways in age-related heart diseases - - EXPERT2016 - ANR-16-ECVD-0002 - ERA-CVD - VALID, and Entreprises lorraines, parties prenantes et Développement Durable (FEDER) (Région Lorraine) - INCOMING
Subjects: Adult, Male, medicine.medical_specialty, Cardiorenal syndrome, medicine.medical_treatment, Cardiac index, Urology, Renal function, Hemodynamics, Heart failure, Heart transplantation, 030204 cardiovascular system & hematology, Kidney, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, medicine, Diseases of the circulatory (Cardiovascular) system, Humans, Renal Insufficiency, 030212 general & internal medicine, Cardiac oedema, Cardiac catheterization, business.industry, Central venous pressure, Original Articles, Middle Aged, medicine.disease, Confidence interval, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Cardiovascular diseases, RC666-701, Original Article, Female, Cardiology and Cardiovascular Medicine, business, Glomerular Filtration Rate
Abstract: International audience; Aims: Abnormal renal function is a common feature in patients on heart transplant waiting lists. This study aimed to identify the haemodynamic parameters associated with decreased estimated glomerular filtration rate (eGFR) in patients listed for heart transplantation (HT) and renal function improvement following HT.Methods and results: A total of 176 adults (52 years old, 81% men) with available right heart catheterization (RHC) listed in our centre for HT between 2014 and 2019 were studied. Cardiac catheterization measurements were obtained at time of HT listing evaluation. Changes in renal function were assessed between RHC and 6 months after HT. Median eGFR was 63 mL/min/1.73 m2 at time of RHC. Central venous pressure > 10 mmHg was associated with a two-fold increase in the likelihood of eGFR < 60 mL/min/1.73 m2 at time of RHC (adjusted odd ratio, 2.2; 95% confidence interval, 1.1-4.7; P = 0.04). In the 134 patients (76%) who underwent HT during follow-up, eGFR decreased by 7.9 ± 29.7 mL/min/1.73 m2 from RHC to 6 months after HT. In these patients, low cardiac index (
Published: 2021

9. Transcorporal vs. bulbar artificial urinary sphincter implantation in male patients with fragile urethra

Author: Franck Bruyère, T. Tricard, Pierre Lecoanet, Baptiste Poussot, Nicolas Hermieu, Alain Ruffion, Victor Gaillard, Hervé Monsaint, Grégoire Capon, Christian Saussine, Xavier Biardeau, Damien Robin, Daniel Chevallier, L. Corbel, Thibaut Brierre, Alice Pitout, Priscilla Bertrand-Leon, Jean-Nicolas Cornu, Benoit Peyronnet, Mehdi El-Akri, Hugo Dupuis, Xavier Gamé, I. Bentellis, Tiffany Cousin, Jean-François Hermieu, Florian Beraud, CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Strasbourg, Centre Hospitalier Universitaire Toulouse (CHU Toulouse), CHU Bordeaux [Bordeaux], Service d'urologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service d’urologie, hôpital Bichat-Claude-Bernard, Hôpitaux Universitaires Paris Nord Val de Seine, Centre Hospitalier Universitaire de Reims (CHU Reims), Service d'Urologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'Urologie, andrologie et transplantation rénale [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Clinique Oceane, Vannes, Clinique Plérin, Plérin, Service d'urologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), CHU Toulouse [Toulouse], and Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, medicine.medical_specialty, Urethral stricture, Urology, Population, 030232 urology & nephrology, Urinary incontinence, Risk Assessment, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Prosthesis Implantation, Artificial urinary sphincter, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, medicine, Humans, Risk factor, education, Device Removal, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Aged, 80 and over, education.field_of_study, business.industry, Urethral sphincter, Middle Aged, medicine.disease, Surgery, Urethra, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cuff, Urinary Sphincter, Artificial, medicine.symptom, business
Abstract: To compare transcorporal vs bulbar artificial urinary sphincter (AUS) implantation in men with fragile urethra and to investigate the risk factors of AUS explantation in this population. The charts of all male patients who had an AUS implantation between 2004 and 2020 in 16 centers were reviewed retrospectively. The primary endpoint was device explantation-free survival. Only patients with a fragile urethra were included in the present analysis. Fragile urethra was defined as a urethra carrying a high risk of cuff erosion because of prior radiotherapy and/or history of AUS explantation and/or history of urethral stricture surgery. The patients were divided in two groups according to the implantation site: bulbar vs transcorporal. 464 patients were included for analysis. 88 patients underwent a transcorporal AUS implantation and 376 underwent a bulbar AUS implantation. Explantation-free survival was similar in both groups (estimated 5-year explantation free survival rates 55.3% vs. 58.4%; p=0.98). In the subgroup of patients with a history of previous AUS explantation, transcorporal approach tended to bring longer explantation-free survival (2-year explantation-free survival: 61.9% vs. 58.2%; p=0.096). In multivariate analysis, the only risk factor of shorter explantation-free survival was the history of previous AUS explantation (HR=2.65; p=0.01). Transcorporal AUS implantation was not associated with longer explantation-free survival. History of previous AUS explantation was the only risk factor associated with shorter explantation-free survival and this subgroup of patients may be the only one to draw benefits of transcorporal AUS implantation.
Published: 2021

10. Lenin's Stroke

Author: Laura Mechtouff, Tae-Hee Cho, Norbert Nighoghossian, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), and CarMeN, laboratoire
Subjects: medicine.medical_specialty, business.industry, Ischemic strokes, [SDV]Life Sciences [q-bio], Autopsy, medicine.disease, Atherosclerosis, 3. Good health, Neurosyphilis, [SDV] Life Sciences [q-bio], Stroke, 03 medical and health sciences, Health problems, 0302 clinical medicine, Bolchevik leader, Medicine, Neurology. Diseases of the nervous system, 030212 general & internal medicine, Neurology (clinical), RC346-429, business, Intensive care medicine, 030217 neurology & neurosurgery, Single Case − General Neurology
Abstract: International audience; Lenin's stroke remains a matter of debate. Here, we propose to assess the potential mechanisms. Lenin died on January 21, 1924 at the age of 53 years. Although some doctors suggested that the origin of his health problems was neurosyphilis, the autopsy findings were consistent with a severe atherosclerosis. This process might account for his recurrent ischemic strokes. In view of the family vascular history, an early hereditary atherosclerosis may be proposed.
Published: 2021

11. Safety and efficacy of the Silk flow diverter: Insight from the DIVERSION prospective cohort study

Author: Florent Gariel, Gaultier Marnat, Xavier Barreau, Patrice Menegon, Romain Bourcier, Laurent Pierot, Lauren Spelle, Alain Bonafé, Francis Turjman, Benjamin Gory, Jérôme Berge, Vincent Costalat, Gregory Gascou, Cyril Dargazanli, Sébastien Soize, Georges Metaxas, Jacques Moret, Léon Ikka, Jildaz Caroff, Aymeric Rouchaud, Christian Mihaela, Nidal Benachour, Michel Piotin, Raphaël Blanc, Hocine Redjem, Elisa Pomero, Alessandra Biondi, Christophe Cognard, Anne-Christine Januel, Jean Darcourt, Adrien Guenego, Philippe Tall, Fabrice Bonneville, Charbel Mounayer, Suzana Saleme, Nader Sourour, Frédéric Clarençon, Charlotte Barbier, Denis Herbreteau, Ana-Paula Narata, Richard Bibi, Serge Bracard, René Anxionnat, Anne-Laure Derelle, Romain Tonnelet, Liang Liao, Emmanuel Chabert, Hervé Brunel, Frederic Ricolfi, Hubert Desal, Zsolt Kulcsar, Christian Taschner, Département de Neuro-Radiologie [Bordeaux] (DNR - Bordeaux), CHU Bordeaux [Bordeaux], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire de Reims (CHU Reims), Service de Neuroradiologie [CHU de Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neuroradiologie [Hôpital Gui de Chauliac], Hôpital Gui de Chauliac [Montpellier], Service de neuroradiologie [Lyon], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Département de neuroradiologie diagnostique et thérapeutique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Neuroradiologie Diagnostique et Thérapeutique [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Service de Neuroradiologie interventionnelle [CHU Limoges], CHU Limoges, Service de Neuroradiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Départment de Neuroradiologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de neuroradiologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Clermont-Ferrand, Service de neuroradiologie diagnostique et interventionnelle, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service de neuroradiologie, imagerie des urgences [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), University hospital of Zurich [Zurich], University Hospital Freiburg, Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), and DIVERSION investigators: Vincent Costalat , Gregory Gascou , Cyril Dargazanli, Sébastien Soize, Georges Metaxas, Jacques Moret , Léon Ikka, Jildaz Caroff, Aymeric Rouchaud, Christian Mihaela, Nidal Benachour, Michel Piotin, Raphaël Blanc, Hocine Redjem, Elisa Pomero , Alessandra Biondi, Christophe Cognard, Anne-Christine Januel, Jean Darcourt, Adrien Guenego, Philippe Tall, Fabrice Bonneville , Charbel Mounayer , Suzana Saleme, Nader Sourour, Frédéric Clarençon, Charlotte Barbier, Denis Herbreteau, Ana-Paula Narata, Richard Bibi , Serge Bracard , René Anxionnat , Anne-Laure Derelle, Romain Tonnelet, Liang Liao , Emmanuel Chabert , Hervé Brunel, Frederic Ricolfi, Hubert Desal, Zsolt Kulcsar, Christian Taschner
Subjects: Adult, medicine.medical_specialty, medicine.medical_treatment, Silk, Subgroup analysis, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Aneurysm, Occlusion, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, medicine, Humans, Endovascular treatment, Radiology, Nuclear Medicine and imaging, Prospective Studies, Prospective cohort study, Survival rate, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Flow diverter, Radiological and Ultrasound Technology, business.industry, Endovascular Procedures, Flow diversion, Stent, Intracranial Aneurysm, Middle Aged, medicine.disease, Confidence interval, 3. Good health, Surgery, Treatment Outcome, Stents, Neurology (clinical), Intracranial aneurysms, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract: Background and purpose Flow diverters are considered as an essential tool in the stent-based treatment of complex intracranial aneurysms. We report here a subgroup analysis of the nationwide prospective DIVERSION study to investigate the safety and efficacy of the Silk flow diverter at 12 months follow-up. Methods We performed a subgroup analysis of patients included in the DIVERSION, a national prospective cohort study including all flow diverters placement between 2012 and 2014 in France, and treated with the Silk. The primary outcome was the morbi-mortality at 12 months, including death, morbidity event and aneurysm retreatment within 12 months post-treatment. All reported serious events were adjudicated by an independent Data Safety and Monitoring Board. Satisfactory occlusion was defined as 3 or 4 on Kamran's scale by an independent imaging core laboratory during follow-up. Results A total of 102 procedures involving 101 patients (mean age ± standard deviation, 54.3 ± 13.5 years) harbouring 118 aneurysms (113/118 located in the anterior circulation; mean size 8.2 ± 7.1 mm) were included. During the 12-month follow-up, 34 (33.3%) procedures experienced at least one morbi-mortality event: 3 deaths, 27 morbidity events and 4 retreatments. Overall, 1/3 deaths and 10/27 morbidity events were related to the device and/or the procedure, leading to a specific survival rate and a specific free-morbidity survival rate at 12 months of 98.98% [95% confidence interval, 92.98%–99.86%] and 89.73% [95%CI, 81.71%–94.36%], respectively. The rate of permanent-related neurological deficit was 5.9% within 12 months. One year follow-up imaging showed satisfactory occlusion in 82.2% of cases. Conclusion Flow diversion with the Silk device has a reasonable safety and effectiveness profile for the endovascular treatment of intracranial aneurysms.
Published: 2021

12. Regional myocardial function at preclinical disease stage of hypertrophic cardiomyopathy in female gene variant carriers

Author: Tjeerd Germans, Celine Seegers, Albert C. van Rossum, Pierre Croisille, Patrick Clarysse, Jolanda van der Velden, Rahana Y. Parbhudayal, Cardiology, ACS - Heart failure & arrhythmias, Physiology, Modeling & analysis for medical imaging and Diagnosis (MYRIAD), 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 Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Imagerie et modélisation Vasculaires, Thoraciques et Cérébrales (MOTIVATE)
Subjects: Male, Cardiac function curve, medicine.medical_specialty, TNNT2, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Diastole, Magnetic Resonance Imaging, Cine, 030204 cardiovascular system & hematology, Asymptomatic, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, MYBPC3, MYH7, 0302 clinical medicine, Predictive Value of Tests, Internal medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, Cardiac imaging, Original Paper, medicine.diagnostic_test, business.industry, Myocardium, Hypertrophic cardiomyopathy, Heart, Tissue tagging, Magnetic resonance imaging, Cardiomyopathy, Hypertrophic, medicine.disease, Cardiology, Female, medicine.symptom, Cardiology and Cardiovascular Medicine, business, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing
Abstract: We recently showed more severe diastolic dysfunction at the time of myectomy in female compared to male patients with obstructive hypertrophic cardiomyopathy. Early recognition of aberrant cardiac contracility using cardiovascular magnetic resonance (CMR) imaging may identify women at risk of cardiac dysfunction. To define myocardial function at an early disease stage, we studied regional cardiac function using CMR imaging with tissue tagging in asymptomatic female gene variant carriers. CMR imaging with tissue tagging was done in 13 MYBPC3, 11 MYH7 and 6 TNNT2 gene carriers and 16 age-matched controls. Regional peak circumferential strain was derived from tissue tagging images of the basal and midventricular segments of the septum and lateral wall. Left ventricular wall thickness and global function were comparable between MYBPC3, MYH7, TNNT2 carriers and controls. MYH7 gene variant carriers showed a different strain pattern as compared to the other groups, with higher septal peak circumferential strain at the basal segments compared to the lateral wall, whereas MYBPC3, TNNT2 carriers and controls showed higher strain at the lateral wall compared to the septum. Only subtle gene-specific changes in strain pattern occur in the myocardium preceding development of cardiac hypertrophy. Overall, our study shows that there are no major contractile deficits in asymptomatic females carrying a pathogenic gene variant, which would justify the use of CMR imaging for earlier diagnosis.
Published: 2021

13. Comparison of two delayed strategies for renal replacement therapy initiation for severe acute kidney injury (AKIKI 2): a multicentre, open-label, randomised, controlled trial

Author: Nicolas de Prost, Saber Barbar, Stéphane Gaudry, Jean-Pierre Quenot, Christophe Vinsonneau, Laurent Argaud, Eric Boulet, Didier Thevenin, Didier Dreyfuss, Marion Beuzelin, Adrien Robine, Cyril Cadoz, Steven Grangé, Béatrice La Combe, Dimitri Titeca-Beauport, Julien Mayaux, Julio Badie, Saad Nseir, Guillaume Chevrel, Karim Asehnoune, Florent Poirson, Kada Klouche, Sébastien Moschietto, Guillaume Louis, Guillaume Thiery, Marc Leone, David Hajage, Pascal Andreu, Elisabeth Coupez, Bertrand Pons, Said Lebbah, Jean-Damien Ricard, Jean-Marie Forel, Laurent Martin-Lefevre, Julien Bohé, Guillaume Geri, Sébastien Besset, Karim Lakhal, Nicolas Chudeau, Alain Combes, Bertrand Rozec, Nadia Aissaoui, Guillaume Lacave, Jean Reignier, CarMeN, laboratoire, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), UFR Santé, Médecine et Biologie Humaine (UFR SMBH), Université Sorbonne Paris Nord, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre de Pharmacoépidémiologie de l'AP-HP (Cephepi), 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 Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Laboratoire Informatique, Image et Interaction - EA 2118 (L3I), La Rochelle Université (ULR), Centre Hospitalier Henri Duffaut (Avignon), CHU Amiens-Picardie, Université de Bretagne Sud - Lorient (UBS Lorient), Université de Bretagne Sud (UBS), Centre d'Etudes Lasers Intenses et Applications (CELIA), Université de Bordeaux (UB)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Hôpital Henri Mondor, Laboratoire Sciences Analytiques, Bioanalytiques, et Miniaturisation (LSABM), Chimie-Biologie-Innovation (UMR 8231) (CBI), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier de Dieppe, CH Belfort-Montbéliard, Centre Hospitalier Sud Francilien, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Centre Hospitalier Le Mans (CH Le Mans), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Assistance Publique - Hôpitaux de Marseille (APHM), Centre Hospitalier de Lens, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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), Géomécanique, Matériaux et Structures (GEOMAS), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Service Anesthésie et Réanimation [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Centre Hospitalier de Versailles André Mignot (CHV), Centre d'Investigation Clinique - Innovation Technologique de Lille - CIC 1403 - CIC 9301 (CIC Lille), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Ambroise Paré [AP-HP], 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 Universitaire de Saint-Etienne (CHU de Saint-Etienne), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Service de Réanimation Médicale (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Louis Mourier - AP-HP [Colombes], Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Programme Hospitalier de Recherche Clinique., Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, Université de La Rochelle (ULR), Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Bordeaux (UB), Laboratoire de Tribologie et Dynamique des Systèmes (LTDS), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-École Nationale des Travaux Publics de l'État (ENTPE)-Ecole Nationale d'Ingénieurs de Saint Etienne-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Centre Hospitalier Fleyriat [Bourg en Bresse], Centre Hospitalier Sud Francilien [Corbeil-Essonnes] (CH Sud Francilien), Centre Hospitalier de Béthune Beuvry (CH Béthune Beuvry), Hôpital Nord [CHU - APHM], GH Carnelle Portes de l'Oise, Hôpital Lapeyronie [Montpellier] (CHU), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord
Subjects: medicine.medical_specialty, MESH: Acute Kidney Injury, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Population, 030204 cardiovascular system & hematology, urologic and male genital diseases, MESH: Severity of Illnes Index, 03 medical and health sciences, MESH: Aged, 80 and over, 0302 clinical medicine, Oliguria, Intensive care, Internal medicine, Medicine, MESH: Time-to-Treatment, 030212 general & internal medicine, Renal replacement therapy, education, Blood urea nitrogen, MESH: Aged, education.field_of_study, MESH: Humans, MESH: Middle Aged, business.industry, Hazard ratio, Acute kidney injury, General Medicine, medicine.disease, MESH: Male, MESH: Prospective Studies, 3. Good health, [SDV] Life Sciences [q-bio], MESH: France, MESH: Intensive Care Units, medicine.symptom, MESH: Renal Remplacement Therapy, business, MESH: Female, Kidney disease
Abstract: International audience; BACKGROUND: Delaying renal replacement therapy (RRT) for some time in critically ill patients with severe acute kidney injury and no severe complication is safe and allows optimisation of the use of medical devices. Major uncertainty remains concerning the duration for which RRT can be postponed without risk. Our aim was to test the hypothesis that a more-delayed initiation strategy would result in more RRT-free days, compared with a delayed strategy. METHODS: This was an unmasked, multicentre, prospective, open-label, randomised, controlled trial done in 39 intensive care units in France. We monitored critically ill patients with severe acute kidney injury (defined as Kidney Disease: Improving Global Outcomes stage 3) until they had oliguria for more than 72 h or a blood urea nitrogen concentration higher than 112 mg/dL. Patients were then randomly assigned (1:1) to either a strategy (delayed strategy) in which RRT was started just after randomisation or to a more-delayed strategy. With the more-delayed strategy, RRT initiation was postponed until mandatory indication (noticeable hyperkalaemia or metabolic acidosis or pulmonary oedema) or until blood urea nitrogen concentration reached 140 mg/dL. The primary outcome was the number of days alive and free of RRT between randomisation and day 28 and was done in the intention-to-treat population. The study is registered with ClinicalTrial.gov, NCT03396757 and is completed. FINDINGS: Between May 7, 2018, and Oct 11, 2019, of 5336 patients assessed, 278 patients underwent randomisation; 137 were assigned to the delayed strategy and 141 to the more-delayed strategy. The number of complications potentially related to acute kidney injury or to RRT were similar between groups. The median number of RRT-free days was 12 days (IQR 0-25) in the delayed strategy and 10 days (IQR 0-24) in the more-delayed strategy (p=0·93). In a multivariable analysis, the hazard ratio for death at 60 days was 1·65 (95% CI 1·09-2·50, p=0·018) with the more-delayed versus the delayed strategy. The number of complications potentially related to acute kidney injury or renal replacement therapy did not differ between groups. INTERPRETATION: In severe acute kidney injury patients with oliguria for more than 72 h or blood urea nitrogen concentration higher than 112 mg/dL and no severe complication that would mandate immediate RRT, longer postponing of RRT initiation did not confer additional benefit and was associated with potential harm. FUNDING: Programme Hospitalier de Recherche Clinique.
Published: 2021

14. Prognostic significance of vascular and valvular calcifications in low- and high-gradient aortic stenosis

Author: Eric Durand, Nina Ghigo, Herve Liebgott, Géraud Souteyrand, Loic Boussel, Thierry Lefèvre, Pierre Lantelme, Hélène Eltchaninoff, Brahim Harbaoui, Pierre-Yves Courand, 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)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Modeling & analysis for medical imaging and Diagnosis (MYRIAD), 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)-Université Claude Bernard Lyon 1 (UCBL), Image Science for Interventional Techniques (ISIT), Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Centre National de la Recherche Scientifique (CNRS), Pharmacologie des Dysfonctionnements Endotheliaux et Myocardiques, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Ramsay Santé, 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-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), and Liebgott, Hervé
Subjects: medicine.medical_specialty, aortic stiffness, [SDV]Life Sciences [q-bio], Renal function, TAVR, 030204 cardiovascular system & hematology, Severity of Illness Index, Ventricular Function, Left, Transcatheter Aortic Valve Replacement, TAVI, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Atrial Fibrillation, medicine, Humans, Radiology, Nuclear Medicine and imaging, 030212 general & internal medicine, Retrospective Studies, Ejection fraction, business.industry, Hazard ratio, vascular stiffness, Stroke Volume, Atrial fibrillation, Aortic Valve Stenosis, General Medicine, Prognosis, medicine.disease, outcome, Confidence interval, [SDV] Life Sciences [q-bio], Stenosis, Treatment Outcome, Aortic Valve, cardiovascular system, Cardiology, Aortic stiffness, Cardiology and Cardiovascular Medicine, business
Abstract: Aims In low-gradient aortic stenosis (LGAS), the high valvulo-arterial impedance observed despite low valvular gradient suggests a high vascular load. Thoracic aortic calcifications (TACs) and valvular aortic calcifications (VACs) are, respectively, surrogates of aortic load and aortic valvular gradient. The aim of this study was to compare the respective contributions of TAC and VAC on 3-year cardiovascular (CV) mortality following TAVI in LGAS vs. high-gradient aortic stenosis (HGAS) patients. Methods and results A total of 1396 consecutive patients were included. TAC and VAC were measured on the pre-TAVI CT-scan. About 435 (31.2%) patients had LGAS and 961 (68.8%) HGAS. LGAS patients were more prone to have diabetes, coronary artery disease (CAD), atrial fibrillation (AF), and lower left ventricular ejection fraction (LVEF), P Conclusion TAC plays a major prognostic role in LGAS while VAC remains the key in HGAS patients. This confirms that LGAS is a complex vascular and valvular disease.
Published: 2021

15. Central hypothyroidism during pregnancy in a woman with Graves' disease

Author: Safouane M. Hamdi, Glinoer Daniel, Tanguy Faustine, Philippe Caron, Chikh Karim, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut Fédératif de Biologie (IFB), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Vrije Universiteit Brussel (VUB), and CarMeN, laboratoire
Subjects: medicine.medical_specialty, Pregnancy, Pediatrics, business.industry, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Graves' disease, Pregnancy Complications, medicine.disease, Graves Disease, [SDV] Life Sciences [q-bio], Endocrinology, Hypothyroidism, Internal medicine, medicine, Central hypothyroidism, Humans, Female, business, Graves Disease/complications/drug therapy
Abstract: International audience; No abstract available
Published: 2021

16. Rare diseases of phosphate and calcium metabolism: Crossing glances between nephrology and endocrinology

Author: Aurélia Bertholet-Thomas, Mélodie Mosca, Julie Bernardor, Sandrine Lemoine, Justine Bacchetta, Centre de référence des maladies rénales rares Néphrogones [CHU-HCL, Lyon], Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital l'Archet, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Université de Lyon, and CarMeN, laboratoire
Subjects: Nephrology, X-linked hypophosphatemia, medicine.medical_specialty, Hypoparathyroidism, Hypoparathyroïdie, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Phosphate, 030209 endocrinology & metabolism, Context (language use), Nephrolithiasis, Kidney, urologic and male genital diseases, Hypophosphatémie liée à l’X, Phosphates, Lithiase, 03 medical and health sciences, Hyperphosphatemia, Rare Diseases, 0302 clinical medicine, Endocrinology, Calcium Metabolism Disorders, Internal medicine, medicine, Teriparatide, Humans, Hypercalciuria, Patient Care Team, Calcium metabolism, business.industry, Hyperparathyroidism, Phosphorus Metabolism Disorders, General Medicine, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Hyperparathyroïdie, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Phosphore, Rein, Calcium, Interdisciplinary Communication, business, medicine.drug
Abstract: International audience; Rare diseases of phosphate/calcium metabolism correspond to a wide and heterogeneous spectrum of diseases. Recent knowledge in physiology and genetics has made it possible to better characterize them and to propose attractive therapeutic approaches based on the underlying pathophysiology. These diseases are often at the interface between nephrology and endocrinology. In this spirit of a multidisciplinary care, each specialty can bring its own critical point of view and its own specificities to improve patient care. The objective of this manuscript is to "read" with a nephrologist's point of view the main frameworks of diseases of phosphate/calcium metabolism, to illustrate the three crucial messages of nephro-protection sent to endocrinologists. First, calciuria must be interpreted both in absolute value (concentration hypercalciuria) and in ratio (flow hypercalciuria). Second, renal monitoring of therapies inducing hypercalciuria on kidneys with normal renal function (e.g. active vitamin D analogs or teriparatide) should be systematic. Last, hyperphosphatemia, often latent in hypoparathyroidism and pseudo-hypoparathyroidism, should be detected and at least benefit from dietary measures, in the context of Western diets rich in phosphate hidden in food additives.
Published: 2021

17. Standardization of 18F-FDG–PET/CT According to Deauville Criteria for Metabolic Complete Response Definition in Newly Diagnosed Multiple Myeloma

Author: Elena Zamagni, Cristina Nanni, Luca Dozza, Thomas Carlier, Clément Bailly, Paola Tacchetti, Annibale Versari, Stephane Chauvie, Andrea Gallamini, Barbara Gamberi, Denis Caillot, Francesca Patriarca, Margaret Macro, Mario Boccadoro, Laurent Garderet, Simona Barbato, Stefano Fanti, Aurore Perrot, Francesca Gay, Peter Sonneveld, Lionel Karlin, Michele Cavo, Caroline Bodet-Milin, Philippe Moreau, Françoise Kraeber-Bodéré, Zamagni E., Nanni C., Dozza L., Carlier T., Bailly C., Tacchetti P., Versari A., Chauvie S., Gallamini A., Gamberi B., Caillot D., Patriarca F., Macro M., Boccadoro M., Garderet L., Barbato S., Fanti S., Perrot A., Gay F., Sonneveld P., Karlin L., Cavo M., Bodet-Milin C., Moreau P., Kraeber-Bodere F., Bernardo, Elizabeth, The Institute of Hematology and Oncology L. and A. Seràgnoli [Bologna, Italy], Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Policlinico S. Orsola-malpighi, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO)-Servizio sanitario regionale Emilia-Romagna, Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Santa Croce e Carle Hospital [Cuneo, Italy], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Università degli Studi di Udine - University of Udine [Italie], Laboratoire d'Hématologie Biologique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Università degli studi di Torino = University of Turin (UNITO), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'Hématologie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Università degli Studi di Modena e Reggio Emilia, Università degli studi di Torino (UNITO), and Hematology
Subjects: Cancer Research, [SDV.CAN]Life Sciences [q-bio]/Cancer, Computed tomography, Newly diagnosed, 18F-Fluorodeoxyglucose, FDG, positron emission tomography, PET, computed tomography, CT, minimal residual disease, multiple myeloma, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Deauville Criteria, 18 F-FDG-PET/CT, Medicine, Multiple myeloma, Complete response, 18F-FDG-PET/C, Multiple Myeloma, medicine.diagnostic_test, business.industry, medicine.disease, Standard technique, Minimal residual disease, Oncology, Positron emission tomography, 030220 oncology & carcinogenesis, Fdg pet ct, 18F-FDG, myeloma, Deauville, Nuclear medicine, business, 030215 immunology
Abstract: PURPOSE 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is currently the standard technique to define minimal residual disease (MRD) status outside the bone marrow (BM) in patients with multiple myeloma (MM). This study aimed to define criteria for PET complete metabolic response after therapy, jointly analyzing a subgroup of newly diagnosed transplantation-eligible patients with MM enrolled in two independent European randomized phase III trials (IFM/DFCI2009 and EMN02/HO95). PATIENTS AND METHODS Two hundred twenty-eight patients were observed for a median of 62.9 months. By study design, PET/CT scans were performed at baseline and before starting maintenance (premaintenance [PM]). The five-point Deauville scale (DS) was applied to describe BM (BM score [BMS]) and focal lesion (FL; FL score [FS]) uptake and tested a posteriori in uni- and multivariable analyses for their impact on clinical outcomes. RESULTS At baseline, 78% of patients had FLs (11% extramedullary), 80% with an FS ≥ 4. All patients had BM diffuse uptake (35.5% with BMS ≥ 4). At PM, 31% of patients had visually detectable FLs (2% extramedullary), 24% and 67.7% of them with an FS of 3 and ≥ 4, respectively. At PM, 98% of patients retained residual BM diffuse uptake, which was significantly lower than at baseline (mainly between BMS 2 and 3, BMS was ≥ 4 in only 8.7% of patients). By both uni- and multivariable analysis, FS and BMS < 4 were associated with prolonged progression-free survival (PFS) and overall survival (OS) at PM (OS: hazard ratio [HR], 0.6 and 0.47, respectively; PFS: HR, 0.36 and 0.24, respectively) CONCLUSION FL and BM FDG uptake lower than the liver background after therapy was an independent predictor for improved PFS and OS and can be proposed as the standardized criterion of PET complete metabolic response, confirming the value of the DS for patients with MM.
Published: 2021

18. Stroke patients’ support: evaluation of knowledge, practices and training needs of French community pharmacists

Author: Marie Viprey, Claude Dussart, Sophie Khettar, Audrey Janoly-Dumenil, Jacques Luauté, Gilles Rode, Laura Mechtouff, Julie Haesebaert, Sophie Jacquin-Courtois, Laurent Derex, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Parcours santé systémique (P2S), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Université de Lyon, Research on Healthcare Performance (RESHAPE - Inserm U1290 - UCBL1), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Health Service and Performance Research (HESPER), Hôpital Henry Gabrielle [CHU - HCL], Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), 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), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], CarMeN, laboratoire, Centre de recherche en neurosciences de Lyon (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: Health Knowledge, Attitudes, Practice, medicine.medical_specialty, Cross-sectional study, [SDV]Life Sciences [q-bio], education, Pharmaceutical Science, Pharmacy, Community Pharmacy Services, Pharmacists, Toxicology, 030226 pharmacology & pharmacy, 03 medical and health sciences, Professional Role, 0302 clinical medicine, Humans, Medicine, Pharmacology (medical), Pharmacist knowledge, 030212 general & internal medicine, Survey, Stroke, Pharmacies, Patient counseling, Pharmacology, Modalities, business.industry, Public health, medicine.disease, Community pharmacist, 3. Good health, [SDV] Life Sciences [q-bio], Long-term care, Cross-Sectional Studies, Pharmaceutical care, Family medicine, business, Patient education
Abstract: International audience; Background Stroke represents a major Public Health issue in industrialized countries because of its frequency and severity. In secondary stroke prevention, treatment efficacy is correlated to medication adherence. However, it remains suboptimal in stroke patients. Community pharmacists, in light of their positioning in the care pathway and proximity to patients, can play an essential role in patient support and improving treatment adherence. However, it is currently unknown whether pharmacists are ready to perform this task. Objective Evaluate knowledge, practices and training needs for community pharmacists in therapeutic stroke management to improve long term care for stroke patients. Setting Community pharmacies in the Rhone Alpes region (France). Method We conducted a cross sectional study via a standardized self-assessment questionnaire consisting of 40 questions divided into three parts. The latter was designed by a multidisciplinary team and distributed electronically to community pharmacists of the Rhône-Alpes region (France). Main outcome measure (a) global knowledge score on the pathology, risk factors and clinical care management, (b) description of the support practices for stroke patients, (c) training needs for pharmacists. Results The 104 participants presented a moderate level of knowledge (global score: 12/20 ± 3). Topics best mastered were: pathophysiology, target blood pressure and place of antiplatelets in the therapeutic strategy. Knowledge items that needed improvement were: warning signs correctly identified by 44% of participants, time delay for thrombolysis for which 14% answered correctly, target glycated hemoglobin levels were correct for 41%, and the 3 recommended antihypertensive drug classes were only identified by 5% of participants. Patient education received from pharmacists concerned dosage (89%), treatment adherence (88%), benefits (66%) and administration modalities of medicines (64%), management of risk factors (75% for diet, 73% for physical activity, 70% for smoking and 53% for alcohol). All pharmacists wanted additional training on risk factors and clinical management guidelines. Conclusion Based on this small study, the fragmented knowledge and varied practices promote the need for further training for pharmacists to optimize support of stroke patients. This study promotes the elaboration of training systems adapted to pharmacists' needs. This will help support the development of a targeted pharmaceutical care approach for stroke patients.
Published: 2021

19. Third bariatric procedure for insufficient weight loss or weight regain: how far should we go?

Author: Emmanuel Disse, Maud Robert, Thibault Lunel, Gilles Poncet, Julie Perinel, Sylvain Iceta, Elise Pelascini, Arnaud Pasquer, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Quebec Heart and Lung Institute, Université Laval [Québec] (ULaval), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and CCSD, Accord Elsevier
Subjects: Adult, Reoperation, Weight loss failure, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Revisional surgery, 030209 endocrinology & metabolism, Super obesity, Weight Gain, Logistic regression, Tertiary care, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Weight regain, Weight loss, Weight Loss, medicine, Humans, Obesity, Retrospective Studies, Bariatric surgery, 2. Zero hunger, business.industry, medicine.disease, Obesity, Morbid, 3. Good health, Surgery, [SDV] Life Sciences [q-bio], Malnutrition, Treatment Outcome, Third bariatric procedure, Laparoscopy, 030211 gastroenterology & hepatology, France, medicine.symptom, business, Body mass index
Abstract: International audience; BACKGROUND: Revisional procedures in bariatric surgery are increasing with several debated failure risk factors, such as super obesity and old age. No study has yet evaluated the outcomes and risks of a third bariatric procedure indicated for weight loss failure or weight regain. OBJECTIVES: To assess failure risks of a third bariatric procedure according to Reinhold's criteria (percentage excess weight loss [%EWL] ≤50% and/or body mass index [BMI] ≥35 kg/m(2)). SETTING: A university-affiliated tertiary care center, France. METHODS: From 2009 to 2019, clinical data and weight loss results of patients who benefited from 3 bariatric procedures for weight loss failure or weight regain were collected prospectively and analyzed using a binary logistic regression. Weight loss failure was defined according to Reinhold's criteria. RESULTS: Among 1401 bariatric procedures performed, 336 patients benefited from 2 or more procedures, and 45 had a third surgery. Eleven patients that were reoperated on because of malnutrition or gastroesophageal reflux disease were excluded from the final analysis. Among 34 patients with 3 procedures because of weight loss failure or regain, mean BMI was 48.3 ± 8.3 kg/m(2), and mean age was 30 ± 10.7 years. Three out of 34 patients (9%) presented a severe complication (Dindo-Clavien IIIb) and 2 (6%) had a minor one. Achieving Reinhold's weight loss criteria after the second bariatric procedure was a significant predictor of success of the third procedure (β = 2.9 ± 1.3 S.E.). CONCLUSION: Not reaching Reinhold's criteria after a second bariatric procedure was identified as a significant risk factor of failure of a third procedure. A third surgery should be carefully discussed especially in case of primary failure of previous procedures.
Published: 2021

20. Towards in vivo imaging of functionally active 5-HT1A receptors in schizophrenia: concepts and challenges

Author: Adrian Newman-Tancredi, Luc Zimmer, Oriane Razakarivony, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (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), Hospices Civils de Lyon (HCL), Neurolixis, Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Rayet, Béatrice, Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)
Subjects: Agonist, medicine.drug_class, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, medicine.medical_treatment, lcsh:RC321-571, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Neuroimaging, medicine, Radioligand, Receptor, Antipsychotic, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Biological Psychiatry, business.industry, medicine.disease, 030227 psychiatry, Psychiatry and Mental health, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Schizophrenia, Serotonin, business, Neuroscience, 030217 neurology & neurosurgery, Preclinical imaging, Biomarkers
Abstract: The serotonin 5-HT1A receptor has attracted wide attention as a target for treatment of psychiatric disorders. Although this receptor is important in the pharmacological mechanisms of action of new-generation antipsychotics, its characterization remains incomplete. Studies based on in vitro molecular imaging on brain tissue by autoradiography, and more recently in vivo PET imaging, have not yielded clear results, in particular due to the limitations of current 5-HT1A radiotracers, which lack specificity and/or bind to all 5-HT1A receptors, regardless of their functional status. The new concept of PET neuroimaging of functionally active G-protein-coupled receptors makes it possible to revisit PET brain exploration by enabling new research paradigms. For the 5-HT1A receptor it is now possible to use [18F]-F13640, a 5-HT1A receptor radioligand with high efficacy agonist properties, to specifically visualize and quantify functionally active receptors, and to relate this information to subjects’ pathophysiological or pharmacological state. We therefore propose imaging protocols to follow changes in the pattern of functional 5-HT1A receptors in relation to mood deficits or cognitive processes. This could allow improved discrimination of different schizophrenia phenotypes and greater understanding of the basis of therapeutic responses to antipsychotic drugs. Finally, as well as targeting functionally active receptors to gain insights into the role of 5-HT1A receptors, the concept can also be extended to the study of other receptors involved in the pathophysiology or therapy of psychiatric disorders.
Published: 2021

21. Association of Interleukin-6 Levels and Futile Reperfusion After Mechanical Thrombectomy

Author: Laura Mechtouff, Elodie Ong, Michel Ovize, Omer Eker, Nathalie Dufay, Norbert Nighoghossian, Alexandre Paccalet, Nathan Mewton, Laurent Derex, Claire Crola Da Silva, Camille Amaz, Thomas Bochaton, Marielle Buisson, Tae-Hee Cho, Yves Berthezène, CarMeN, laboratoire, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre d'Investigation Clinique [Bron] (CIC1407), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupement Hospitalier Est [Bron], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Modeling & analysis for medical imaging and Diagnosis (MYRIAD), 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), Service de neuroradiologie [Lyon], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Neurobiotec [HCL, Lyon], Hospices Civils de Lyon, Departement de Neurologie (HCL), and 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)
Subjects: Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], medicine.medical_treatment, 03 medical and health sciences, 0302 clinical medicine, Modified Rankin Scale, medicine.artery, Internal medicine, Diabetes mellitus, Occlusion, Odds Ratio, medicine, Humans, Treatment Failure, 030212 general & internal medicine, Stroke, Aged, Ischemic Stroke, Thrombectomy, Aged, 80 and over, Interleukin-6, Cerebral infarction, business.industry, Endovascular Procedures, Thrombolysis, Odds ratio, Middle Aged, Prognosis, medicine.disease, [SDV] Life Sciences [q-bio], Treatment Outcome, Multivariate Analysis, Cardiology, Female, Neurology (clinical), Internal carotid artery, business, Medical Futility, 030217 neurology & neurosurgery
Abstract: ObjectiveTo assess whether interleukin-6 (IL-6) level is a marker of futile reperfusion in patients with acute ischemic stroke (AIS) with large vessel occlusion treated with mechanical thrombectomy (MT).MethodsThe Cohort of Patients to Identify Biological and Imaging Markers of Cardiovascular Outcomes in Stroke (HIBISCUS-STROKE) includes patients with AIS treated with MT after MRI. We performed a sequential assessment of IL-6 (admission, 6 hours, 24 hours, 48 hours and 3 months from admission). Among patients with successful reperfusion (Thrombolysis in Cerebral Infarction scale 2b/3), reperfusion was considered effective if 3-month modified Rankin Scale (mRS) score was 0 to 2 and futile if 3-month mRS score was 3 to 6. Our model was adjusted for the main confounding variables.ResultsOne hundred sixty-four patients represent the study population. One hundred thirty-three patients had successful reperfusion (81.1%), while in 46 (34.6%), reperfusion was classified as futile. In single-variable analyses, high IL-6 levels at 6, 24, and 48 hours in combination with a higher age, a prestroke mRS score >2, a history of hypertension or diabetes, lack of current smoking, a higher baseline NIH Stroke Scale score, the absence of associated intravenous thrombolysis, an intracranial internal carotid artery or a tandem occlusion, and an increased infarct growth were associated with futile reperfusion. After multivariable analyses, a high IL-6 level at 24 hours (odds ratio 6.15, 95% confidence interval 1.71–22.10) remained associated with futile reperfusion.ConclusionsIL-6 is a marker of futile reperfusion in the setting of MT.
Published: 2020

22. Characteristics of IDH-mutant gliomas with non-canonical IDH mutation

Author: Poetsch, L., Bronnimann, C., Loiseau, H., Frénel, J., Siegfried, A., Seizeur, R., Gauchotte, G., Cappellen, D., Carpentier, C., Figarella‑Branger, Dominique, Eimer, S., Meyronet, D., Ducray, F., Network, POLA, Rigaud, V., CHU Bordeaux [Bordeaux], Imagerie moléculaire et thérapies innovantes en oncologie (IMOTION), Université de Bordeaux (UB), CRLCC René Gauducheau, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de neurochirurgie [Brest], Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Service d’Anatomie Pathologique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université - Département de neurologie 2 - Mazarin, 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), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Anatomie Pathologique-Neuropathologique [AP-HM Hôpital La Timone], Hôpital de la Timone [CHU - APHM] (TIMONE), Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de neuro-oncologie [Hôpital Pierre Wertheimer - HCL], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Cancer Research, medicine.medical_specialty, IDH1, [SDV]Life Sciences [q-bio], Mutant, IDH2, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Glioma, Internal medicine, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, Family history, neoplasms, ComputingMilieux_MISCELLANEOUS, Brain Neoplasms, business.industry, Cancer, Prognosis, medicine.disease, Combined Modality Therapy, Isocitrate Dehydrogenase, nervous system diseases, 3. Good health, Idh mutation, Survival Rate, Neurology, Oncology, 030220 oncology & carcinogenesis, Mutation, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: Approximately 10% of IDH-mutant gliomas harbour non-canonical IDH mutations (non-p.R132H IDH1 and IDH2 mutations). The aim of this study was to analyse the characteristics of non-canonical IDH-mutant gliomas. We retrospectively analysed the characteristics of 166 patients with non-canonical IDH mutant gliomas and compared them to those of 155 consecutive patients with IDH1 p.R132H mutant gliomas. The median age at diagnosis was 38 years in patients with non-canonical IDH mutant gliomas and 43 years in glioma patients with IDH1 p.R132H-mutant tumours. Family history of cancer was more frequent among glioma patients harbouring non-canonical IDH mutations than in patients with IDH1 p.R132H mutations (22.2% vs 5.1%; P
Published: 2020

23. Consensus Guidelines of the French Society of Neuroradiology (SFNR) on the use of Gadolinium-Based Contrast agents (GBCAs) and related MRI protocols in Neuroradiology

Author: René Anxionnat, Myriam Edjlali-Goujon, Suzana Saleme, Hubert Desal, Nadya Pyatigorskaya, Stéphane Kremer, Douraied Ben Salem, Claire Boutet, Apolline Kazemi, Gregoire Boulouis, François Cotton, Olivier Clément, Basile Kerleroux, Jérôme Berge, Augustin Lecler, François Lersy, CCSD, Accord Elsevier, Les Hôpitaux Universitaires de Strasbourg (HUS), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), GHU Paris Psychiatrie et Neurosciences, 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Neuro-Radiologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Bordeaux [Bordeaux], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), CHU Lille, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Fondation Ophtalmologique Adolphe de Rothschild [Paris], CHU Limoges, Laboratoire de Traitement de l'Information Medicale (LaTIM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), 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), Hospices Civils de Lyon (HCL), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), 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), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], Gadolinium, Gadolinium-based contrast agents, Contrast Media, chemistry.chemical_element, Neuroimaging, Recommendations, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Pituitary adenoma, medicine, Humans, Radiology, Nuclear Medicine and imaging, Neuroradiology, Intracerebral hemorrhage, Radiological and Ultrasound Technology, medicine.diagnostic_test, business.industry, Multiple sclerosis, Magnetic resonance imaging, medicine.disease, Magnetic Resonance Imaging, 3. Good health, [SDV] Life Sciences [q-bio], Venous thrombosis, chemistry, Nephrogenic systemic fibrosis, France, Neurology (clinical), Radiology, business, Brain MRI protocols, 030217 neurology & neurosurgery
Abstract: International audience; Gadolinium-based contrast agents (GBCAs) are used in up to 35% of magnetic resonance imaging (MRI) examinations and are associated with an excellent safety profile. Nevertheless, two main issues have arisen in the last two decades: the risk of nephrogenic systemic fibrosis and the risk of gadolinium deposition and retention. As a first step, this article reviews the different categories of GBCAs available in neuroradiology, their issues, and provides updates regarding the use of these agents in routine daily practice. Recent advances in MRI technology, as well as the development of new MRI sequences, have made GBCA injection avoidable in many indications, especially in patients with chronic diseases when iterative MRIs are required and when essential diagnostic information can be obtained without contrast enhancement. These recent advances also lead to changes in recommended MRI protocols. Thus, in a second step, this review focuses on consensus concerning brain MRI protocols in 10 common situations (acute ischemic stroke, intracerebral hemorrhage, cerebral venous thrombosis, multiple sclerosis, chronic headache, intracranial infection, intra- and extra-axial brain tumors, vestibular schwannoma and pituitary adenoma). The latter allowing the standardization of practices in neuroradiology. Recommendations were also made concerning the use of GBCAs in neuroradiology, based on evidence in the literature and/or by consensus between the different coauthors.
Published: 2020

24. Impact of Arterial Blood Pressure on Ultrasound Hemodynamic Assessment of Aortic Valve Stenosis Severity

Author: Hélène Thibault, Marion Rosset, Lisa Green, Gilles Rioufol, Gérard Finet, François Derimay, Ahmad Hayek, 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), 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), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and CCSD, Accord Elsevier
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], Dimensionless index, Hemodynamics, 030204 cardiovascular system & hematology, Flow rate, Severity of Illness Index, Ventricular Function, Left, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Afterload, Mean transaortic gradient, Internal medicine, Aortic valve area, medicine, Humans, Arterial Pressure, Radiology, Nuclear Medicine and imaging, Prospective Studies, Ejection fraction, business.industry, Aortic stenosis, Ultrasound, afterload, Stroke Volume, Aortic Valve Stenosis, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Stenosis, medicine.anatomical_structure, Blood pressure, Echocardiography, Ventricle, Aortic Valve, Aortic valve stenosis, Cardiology, Cardiology and Cardiovascular Medicine, business
Abstract: International audience; BACKGROUND: Aortic stenosis (AS) severity assessment is based on several indices. Aortic valve area (AVA) is subject to inaccuracies inherent to the measurement method, while velocities and gradients depend on hemodynamic status. There is controversy as to whether blood pressure directly affects common indices of AS severity. OBJECTIVES: The study objective was to assess the effect of systolic blood pressure (SBP) variation on AS indices, in a clinical setting. METHODS: A prospective, single-center study included 100 patients with at least moderately severe AS with preserved left ventricle ejection fraction. Patients underwent ultrasound examination during which AS severity indices were collected, with three hemodynamic conditions: (1) low SBP: \textless120 mm Hg; (2) intermediate SBP: between 120 and 150 mm Hg; (3) high SBP: ≥150 mm Hg. For each patient, SBP profiles were obtained by injection of isosorbide dinitrate or phenylephrine. RESULTS: At baseline state, 59% presented a mean gradient (G(mean)) ≥ 40 mm Hg, 44% a peak aortic jet velocity (V(peak)) ≥4 m/sec, 66% a dimensionless index (DI) ≤0.25, and 87% an indexed AVA (AVAi) ≤ 0.6 cm(2)/m(2). Compared with intermediate and low SBP, high SBP induced a significant decrease in G(mean) (39 ± 12 vs 43 ± 12 and 47 ± 12 mm Hg, respectively; P \textless .05) and in V(peak) (3.8 ± 0.6 vs 4.0 ± 0.6 and 4.2 ± 0.6 mm Hg; P \textless .05). Compared with the baseline measures, in 16% of patients with an initial G(mean)\textless 40 mm Hg, gradient rose above 40 mm Hg after optimization of the afterload (low SBP; P \textless .05). Conversely, DI and AVAi did not vary with changes in hemodynamic conditions. Flow rate, not stroke volume was found to impact G(mean) and V(peak) but not AVA and DI (P \textless .05). CONCLUSIONS: Hemodynamic conditions may affect the AS ultrasound assessment. High SBP, or afterload, leads to an underestimation of AS severity when based on gradients and velocities. Systolic blood pressure monitoring and control are crucial during AS ultrasound assessment.
Published: 2020

25. Progressive multifocal leukoencephalopathy: MRI findings in HIV-infected patients are closer to rituximab- than natalizumab-associated PML

Author: Caroline Papeix, Elisabeth Maillart, Morgane Solis, Caroline Houillier, Philippe Kerschen, Manel Alleg, Jerome Tamburini Bonnefoy, Xavier Roussel, Bertrand Bourre, Céline Kennel, Stéphane Kremer, Jean-Pierre Marolleau, Philippe Agape, Guido Ahle, Adrien Chauchet, François Cotton, Alexis Caulier, Xavier Leclerc, Patrick Vermersch, Cécile Chabrot, Béatrice Claise, Guillaume Martin-Blondel, Sandra Malak, Samira Fafi-Kremer, Seyyid Baloglu, Jérôme De Seze, Fabrice Bonneville, Jean-Pierre Pruvo, Les Hôpitaux Universitaires de Strasbourg (HUS), Laboratoire de Virologie [Strasbourg], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), 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)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier de Luxembourg [Luxembourg] (CHL), CHU Rouen, Normandie Université (NU), Service de Neurologie [Hôpitaux Civils de Colmar], Hôpitaux Civils Colmar, Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Departement de Neuroradiologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), CHU Clermont-Ferrand, Institut Curie - Saint Cloud (ICSC), Service Maladies infectieuses et tropicales [CHU Toulouse], Pôle Inflammation, infection, immunologie et loco-moteur [CHU Toulouse] (Pôle I3LM Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service Neuroradiologie Diagnostique et Thérapeutique [CHU Toulouse], Pôle imagerie médicale [CHU Toulouse], Laboratoire d'Hématologie [CHU Amiens], CHU Amiens-Picardie, AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, CHU Limoges, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital de Hautepierre [Strasbourg], Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Service de neurologie 1 [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), Service de neurologie 2 [CHU Pitié-Salpêtrière], Institut Curie [Saint-Cloud], Service des maladies infectieuses et tropicales [Toulouse], Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de neuroradiologie [CHU Toulouse], CHU Toulouse [Toulouse], Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA), Service de Radiologie (Hôpitaux Universitaires de Strasbourg), Laboratoire de Virologie Médicale [Strasbourg], CHU Strasbourg, Université de Lyon, Centre Hospitalier Universitaire de Rouen, University of Rouen, Rouen, France, University of Lille, Univ. Lille, Inserm, CHU Lille, U1172 - Lille Neurosciences & Cognition, F-59000 Lille, France, Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Lille, Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU de Clermont-Ferrand, université Clermont-Auvergne, Service des maladies infectieuses et tropicales[Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Service d'Hématologie Clinique [CHU Amiens], Centre Hospitalier Universitaire de Besançon (CHU Besançon), Service of Neurologie - Centres Mémoire de Ressources et de Recherche (Hôpitaux Universitaires de Strasbourg ) (CMRR), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-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), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: MESH: Leukoencephalopathy, Progressive Multifocal* / diagnostic imaging, medicine.medical_specialty, Pathology, medicine.medical_treatment, [SDV]Life Sciences [q-bio], viruses, MESH: Natalizumab / adverse effects, HIV Infections, 030218 nuclear medicine & medical imaging, MESH: Magnetic Resonance Imaging, Lesion, 03 medical and health sciences, 0302 clinical medicine, Natalizumab, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Progressive multifocal leukoencephalopathy, medicine, MESH: HIV Infections* / complications, Humans, Radiology, Nuclear Medicine and imaging, Neuroradiology, Retrospective Studies, Chemotherapy, MESH: Humans, business.industry, Leukoencephalopathy, Progressive Multifocal, virus diseases, Brain, Immunosuppression, MESH: Retrospective Studies, General Medicine, MESH: HIV Infections* / drug therapy, medicine.disease, Magnetic Resonance Imaging, MESH: Rituximab / adverse effects, 3. Good health, 030220 oncology & carcinogenesis, MESH: Leukoencephalopathy, Progressive Multifocal* / chemically induced, Rituximab, MESH: Brain / diagnostic imaging, Radiology, medicine.symptom, Neuro, Complication, business, medicine.drug
Abstract: To compare brain MRI findings in progressive multifocal leukoencephalopathy (PML) associated to rituximab and natalizumab treatments and HIV infection. In this retrospective, multicentric study, we analyzed brain MRI exams from 72 patients diagnosed with definite PML: 32 after natalizumab treatment, 20 after rituximab treatment, and 20 HIV patients. We compared T2- or FLAIR-weighted images, diffusion-weighted images, T2*-weighted images, and contrast enhancement features, as well as lesion distribution, especially gray matter involvement. The three PML entities affect U-fibers associated with low signal intensities on T2*-weighted sequences. Natalizumab-associated PML showed a punctuate microcystic appearance in or in the vicinity of the main PML lesions, a potential involvement of the cortex, and contrast enhancement. HIV and rituximab-associated PML showed only mild contrast enhancement, punctuate appearance, and cortical involvement. The CD4/CD8 ratio showed a trend to be higher in the natalizumab group, possibly mirroring a more efficient immune response. Imaging features of rituximab-associated PML are different from those of natalizumab-associated PML and are closer to those observed in HIV-associated PML. • Nowadays, PML is emerging as a complication of new effective therapies based on monoclonal antibodies. • Natalizumab-associated PML shows more inflammatory signs, a perivascular distribution “the milky way,” and more cortex involvement than rituximab- and HIV-associated PML. • MRI differences are probably related to higher levels of immunosuppression in HIV patients and those under rituximab therapy.
Published: 2020

26. Characteristics and outcomes of acute respiratory distress syndrome related to COVID-19 in Belgian and French intensive care units according to antiviral strategies: the COVADIS multicentre observational study

Author: David Grimaldi, Nadia Aissaoui, Gauthier Blonz, Giuseppe Carbutti, Romain Courcelle, Stephane Gaudry, Aurelie Gaultier, Alain D’hondt, Julien Higny, Geoffrey Horlait, Sami Hraiech, Laurent Lefebvre, Francois Lejeune, Andre Ly, Michael Piagnerelli, Bertrand Sauneuf, Nicolas Serck, Thibaud Soumagne, Piotr Szychowiak, Julien Textoris, Benoit Vandenbunder, Christophe Vinsonneau, Jean- Baptiste Lascarrou, for the COVADIS study group, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Services des soins intensifs, Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), 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), Centre Hospitalier Départemental site de la Roche-sur-Yon (CHD de la Roche-sur-Yon), hospital universitaire de Mons-Hainaut, Hopital de Jolimont, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Plateforme de Méthodologie et Biostatistique, Direction de la Recherche [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Ambroise Paré [Mons, Belgium], CHU Dinant-Godinne UCL Namur [Yvoir, Belgique], Hôpital Nord [CHU - APHM], Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Centre Hospitalier du Pays d'Aix, 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), Université libre de Bruxelles (ULB), Grand Hôpital de Charleroi [Belgium], Service de Réanimation Polyvalente [CHPC - Site Louis Pasteur], Site Louis Pasteur [CHPC], CH Centre Hospitalier Public du Cotentin (CHPC)-CH Centre Hospitalier Public du Cotentin (CHPC), Saint Pierre clinic of Ottignies (CSPO), Saint Pierre clinic of Ottignies, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Médecine Intensive et Réanimation [Tours], 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), Réseau CRICS-TRIGGERSEP [CHRU Tours] (F-CRIN research network), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hospices Civils de Lyon (HCL), Laboratoire Commun de Recherche Hospices Civils de Lyon – bioMérieux (Cancer Biomarkers Research Group), Hospices Civils de Lyon (HCL)-BIOMERIEUX, Hôpital Privé d'Antony, Centre Hospitalier de Béthune (CH Béthune), GHT de l'Artois, and COVADIS study group: Patrick Biston, Gwenhael Colin, Oriane de Maere, Nathan Ebstein, Stephan Ehrmann, Frederic Foret, Lionel Haentjens, Thibault Helbert, Jean-Baptiste Mesland, Celine Monard, Nicolas Mongardon, Gregoire Ottavy, Thomas Pasau, Gael Piton, Ester Ponzetto, Caroline Sejourne, Morgane Snacken, Xavier Souloy, Aude Sylvestre, Nicolas Tartrat, Cedric Vanbrussel
Subjects: ARDS, medicine.medical_specialty, medicine.medical_treatment, Remdesivir, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Lopinavir, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Intensive care, Internal medicine, medicine, 030212 general & internal medicine, Renal replacement therapy, Mechanical ventilation, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Ritonavir, business.industry, Research, Acute kidney injury, lcsh:Medical emergencies. Critical care. Intensive care. First aid, lcsh:RC86-88.9, medicine.disease, Cohort, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, medicine.drug, Hydroxychloroquine
Abstract: Background Limited data are available regarding antiviral therapy efficacy in most severe patients under mechanical ventilation for Covid-19-related acute respiratory distress syndrome (ARDS). Methods Comparison of antiviral strategies (none, hydroxychloroquine (OHQ), lopinavir/ritonavir (L/R), others (combination or remdesivir) in an observational multicentre cohort of patients with moderate-to-severe Covid-19 ARDS. The primary endpoint was the number of day 28 ventilator-free days (VFD). Patients who died before d28 were considered as having 0 VFD. The variable was dichotomized into “patients still ventilated or dead at day 28” versus “patients weaned and alive at day 28”. Results We analyzed 415 patients (85 treated with standard of care (SOC), 57 with L/R, 220 with OHQ, and 53 others). The median number of d28-VFD was 0 (IQR 0–13) and differed between groups (P = 0.03), SOC patients having the highest d28-VFD. After adjustment for age, sex, Charlson Comorbidity Index, PaO2/FiO2 ratio and plateau pressure and accounting for center effect with a generalized linear mixed model, none of the antiviral strategies increased the chance of being alive and weaned from MV at day 28 compared to the SOC strategy (OR 0.48 CI95% (0.18–1.25); OR 0.96 (0.47–2.02) and OR 1.43 (0.53–4.04) for L/R, OHQ and other treatments, respectively). Acute kidney injury during ICU stay was frequent (55%); its incidence was higher in patients receiving lopinavir (66 vs 53%, P = 0.03). After adjustment for age, sex, BMI, chronic hypertension and chronic renal disease, the use of L/R was associated with an increased risk of renal replacement therapy (RRT). (OR 2.52 CI95% 1.16–5.59). Conclusion In this multicentre observational study of moderate-to-severe Covid-19 ARDS patients, we did not observe any benefit among patients treated with OHQ or L/R compared with SOC. The use of L/R treatment was associated with an increased need for RRT. Take home message Neither hydroxychloroquine nor lopinavir/ritonavir as COVID-19 antiviral treatment is associated with higher ventilator-free days at day 28 when compared with standard of care (no antiviral treatment) in ICU patients under invasive mechanical ventilation. Lopinavir/ritonavir is associated with an increased risk of renal replacement therapy requirement. Tweet COVID-19: Insights from ARDS cohort: no signal of efficacy of any antiviral drugs. Lopinavir/ritonavir may be associated with need for RRT
Published: 2020

27. Transcriptomic and immunohistochemical approaches identify HLA-G as a predictive biomarker of gestational choriocarcinoma resistance to monochemotherapy

Author: Fabienne Allias, Benoit You, Touria Hajri, Mojgan Devouassoux-Shisheboran, François Mallet, François Golfier, Jérôme Massardier, Sophie Patrier, Jonathan Lopez, Pierre-Adrien Bolze, Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques - EA 7426 (PI3), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), BIOMERIEUX, Université de Lyon, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de Pathologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de gynécologie obstétrique, Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), and CCSD, Accord Elsevier
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], HLA-G, Gestational choriocarcinoma, Malignant transformation, 0302 clinical medicine, Pregnancy, Antineoplastic Combined Chemotherapy Protocols, Choriocarcinoma, reproductive and urinary physiology, Etoposide, Gestational trophoblastic neoplasia, Obstetrics and Gynecology, Hydatidiform Mole, Middle Aged, Immunohistochemistry, female genital diseases and pregnancy complications, 3. Good health, [SDV] Life Sciences [q-bio], Oncology, 030220 oncology & carcinogenesis, Uterine Neoplasms, embryonic structures, Female, Chemoresistance, medicine.drug, Adult, Vincristine, Cyclophosphamide, Antineoplastic Agents, Young Adult, 03 medical and health sciences, Predictive Value of Tests, Biomarkers, Tumor, medicine, Humans, HLA-G Antigens, business.industry, Hydatidiform moles, medicine.disease, Methotrexate, 030104 developmental biology, Drug Resistance, Neoplasm, Cancer research, Transcriptome, business
Abstract: International audience; Objective: Using a transcriptional approach on tissue samples, we sought to identify predictive biomarkers of post molar malignant transformation, and of choriocarcinoma chemosensitivity to mono- (methotrexate or actinomycin D) or polychemotherapy [EMA(Etoposide, Methotrexate, Actinomycin D)-CO(Cyclophosphamide, Vincristine) and EMA-EP(Etoposide, Cisplatine)] regimens.Methods: We studied the expression of a 760-gene panel (PanCancer Pathway) related to oncogenesis and immune tolerance in tissue samples of complete hydatidiform moles and gestational choriocarcinoma.Results: We did not identify any differentially expressed gene between moles with post molar malignant transformation in choriocarcinoma (n = 14) and moles with remission (n = 20). In monochemoresistant choriocarcinoma (n = 34), four genes (HLA-G, COL27A1, IL1R2 and GLI3) had a significantly reduced expression and one (THEM4) had an increased expression [FDR (false discovery rate) adjusted p-value ≤ 0.05] when compared to monochemosensitive choriocarcinoma (n = 9). The proportion of trophoblast cells and the intensity of immunohistochemical HLA-G expression were reduced in monochemoresistant choriocarcinoma (p < 0.05). In polychemoresistant choriocarcinoma (n = 20) we did not identify differentially expressed genes with an FDR adjusted p-value ≤ 0.05 when compared to polychemosensitive choriocarcinoma (n = 15). Gene pathway analysis revealed a predicted activation of IFN ᵞ in monochemoresistant choriocarcinoma and inhibited IL2 and TNF in polychemoresistant choriocarcinoma. The main biological functions predicted to be altered in chemoresistant choriocarcinoma were related to immunological homeostasis and leukopoiesis.Conclusion: HLA-G is a strong candidate gene to predict choriocarcinoma resistance to monochemotherapy and that further studies are required to implement its routine quantification in the decision process for the management of gestational choriocarcinoma.
Published: 2020

28. Type 1 Diabetes in People Hospitalized for COVID-19: New Insights From the CORONADO Study

Author: Sandrine Lablanche, Florence Galtier, Pierre Leroy, Vincent Dubée, Dominique Bonnefont-Rousselot, Patrick Saulnier, Matthieu Wargny, Manuel Etienne, Patrice Darmon, Anne-Laure Borel, Jean-Louis LAPLANCHE, Olivier Lesieur, Bertrand Cariou, Malak Taher, Lydia GUITTET, Vincent Minville, BRUNO MOURVILLIER, Jean-Pierre QUENOT, Bernard Bonnotte, Lucien Marchand, Team2 Carmen, Veronique Kerlan, Pascal Reynier, Nadia Sabbah, Matthieu PICHELIN, Jean-Charles Aurégan, Guillaume Martin-Blondel, Olivier Bourron, Blandine Rammaert, Pierre-Edouard Fournier, Coralie Amadou, Giulia Chinetti, Jean-Christophe Lagier, Didier Raoult, Centre hospitalier universitaire de Nantes (CHU Nantes), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), 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], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), 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 Hospitalier Sud Francilien, Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service d'endocrinologie, diabétologie et nutrition [CHU Bichat], 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)-Université Paris Cité (UPCité), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), 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), Pathogénèse et contrôle des infections chroniques (PCCI), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Diabétologie [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), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), CH Evry-Corbeil, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), 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), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Service de diabétologie [CHU Pitié-Salpétrière], Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Paris (UP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Gestionnaire, Hal Sorbonne Université
Subjects: Male, Pediatrics, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Pneumonia, Viral, Population, 030209 endocrinology & metabolism, law.invention, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, law, Diabetes mellitus, Internal Medicine, medicine, Clinical endpoint, Humans, 030212 general & internal medicine, education, Pandemics, Case report form, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, Glycated Hemoglobin, Advanced and Specialized Nursing, Inpatients, Type 1 diabetes, education.field_of_study, business.industry, e-Letters: Observations, COVID-19, Middle Aged, Prognosis, medicine.disease, Respiration, Artificial, Intensive care unit, 3. Good health, [SDV] Life Sciences [q-bio], Diabetes Mellitus, Type 2, Hypertension, Etiology, Female, Observational study, Coronavirus Infections, business
Abstract: Since the start of the coronavirus disease 2019 (COVID-19) pandemic, patients with diabetes were rapidly recognized as a high-risk population for severe disease. Indeed, a high prevalence of diabetes among patients with COVID-19 who required hospitalization has been consistently reported, reaching 33.8% in 5,700 people hospitalized for COVID-19 in the New York City area (1). In addition, diabetes was associated with more than a doubled risk of intensive care unit (ICU) admission and more than a tripled risk of death (2). However, precise data regarding the type of diabetes are scarce. We report here the clinical characteristics and early prognosis of patients with type 1 diabetes (T1D) hospitalized for COVID-19 in the nationwide multicenter observational CORONADO (Coronavirus SARS-CoV-2 and Diabetes Outcomes) study (3). The aim of the CORONADO study was to describe the phenotypic characteristics and prognosis of patients with diabetes admitted with COVID-19 between 10 March and 10 April 2020 in 68 French hospitals. The protocol (ClinicalTrials.gov reg. no. NCT04324736) obtained all regulatory approvals as recently described (3). Inclusion criteria were 1 ) hospitalization for biologically and/or clinically/radiologically attested COVID-19 and 2 ) personal history of diabetes or newly diagnosed diabetes on admission. The composite primary end point combined tracheal intubation for mechanical ventilation and/or death on day 7 (D7). Secondary outcomes included death, tracheal intubation, and discharge on D7. Classification of diabetes was recorded in the electronic case report form as noted in the medical file by the physician in charge of the patient. In the present subanalysis, patients in whom diabetes was diagnosed on admission were excluded since the etiological diagnosis had not been formally established. All cases noted as T1D were carefully reviewed by local investigators and the steering committee …
Published: 2020

29. Inhibition of Osteoclast Differentiation by 1. <scp>25‐D</scp> and the Calcimimetic <scp>KP2326</scp> Reveals 1. <scp>25‐D</scp> Resistance in Advanced <scp>CKD</scp>

Author: Irma Machuca-Gayet, Justine Bacchetta, Olivier Peyruchaud, Diane Platel, Julie Bernardor, Sacha Flammier, Ségolène Gaillard, Bruno Ranchin, Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Référence des Maladies Rénales Rares, Hospices Civil de Lyon, Université Nice Sophia Antipolis - Faculté de Médecine (UNS UFR Médecine), 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), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Centre d'Investigation Clinique [Bron] (CIC1407), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupement Hospitalier Est [Bron], Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Université de Lyon, and Machuca-Gayet, Irma
Subjects: 0301 basic medicine, medicine.medical_specialty, Calcimimetic, ETELCALCETIDE, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Osteoclasts, 030209 endocrinology & metabolism, Bone resorption, VITAMIN D, 03 medical and health sciences, 0302 clinical medicine, Osteoclast, Internal medicine, medicine, Vitamin D and neurology, Humans, Orthopedics and Sports Medicine, Osteodystrophy, Bone Resorption, Renal Insufficiency, Chronic, Vitamin D, Child, OSTEOCLAST, Etelcalcetide, biology, CHRONIC KIDNEY DISEASE, business.industry, Macrophage Colony-Stimulating Factor, RANK Ligand, Cell Differentiation, medicine.disease, SECONDARY HYPERPARATHYROIDISM, [SDV] Life Sciences [q-bio], 030104 developmental biology, medicine.anatomical_structure, Endocrinology, RANKL, Leukocytes, Mononuclear, biology.protein, Secondary hyperparathyroidism, business
Abstract: International audience; Active vitamin D analogs and calcimimetics are the main therapies used for treating secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD). Peripheral blood mononuclear cells of 19 pediatric patients with CKD1-5D and 6 healthy donors (HD) were differentiated into mature osteoclasts with receptor activator of NF-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). The effects of single or combined treatment with active vitamin D (1.25-D) and/or calcimimetic KP2326 were evaluated on osteoclastic differentiation and osteoclastic-mediated bone resorption. Although 1.25-D inhibited osteoclastic differentiation, a significant resistance to 1.25-D was observed when glomerular filtration rate decreased. A significant albeit less important inhibitory effect of KP2326 on osteoclastic differentiation was also found both in cells derived from HD and CKD patients, through a putative activation of the Erk pathway. This inhibitory effect was not modified by CKD stage. Combinatorial treatment with 1.25-D and KP2326 did not result in synergistic effects. Last, KP2326 significantly inhibited osteoclast-mediated bone resorption. Both 1.25-D and KP2326 inhibit osteoclastic differentiation, however, to a different extent. There is a progressive resistance to 1.25-D in advanced CKD that is not found with KP2326. KP2326 also inhibits bone resorption. Given that 1.25-D has no effect on osteoclastic resorption activity and that calcimimetics also have direct anabolic effects on osteoblasts, there is an experimental rationale that could favor the use of decreased doses of 1.25-D with low doses of calcimimetics in SHPT in dialysis to improve the underlying osteodystrophy. However, this last point deserves confirmatory clinical studies. © 2020 American Society for Bone and Mineral Research.
Published: 2020

30. Phosphorylation of cyclophilin D at serine 191 regulates mitochondrial permeability transition pore opening and cell death after ischemia-reperfusion

Author: Stephen Hurst, Maya Dia, Fabrice Gonnot, Claire Crola Da Silva, Ludovic Gomez, Shey-Shing Sheu, Jefferson (Philadelphia University + Thomas Jefferson University), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA2R01HL0936711R01HL1372661R01HL122124T32AA007463French National Research Agency (ANR)16-CE17-0020-01, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and CarMeN, laboratoire
Subjects: Male, 0301 basic medicine, Cancer Research, Programmed cell death, Oligomycin, [SDV]Life Sciences [q-bio], Immunology, Mutant, Myocardial Reperfusion Injury, 030204 cardiovascular system & hematology, Mitochondrial Membrane Transport Proteins, Article, Serine, Mice, 03 medical and health sciences, Cellular and Molecular Neuroscience, chemistry.chemical_compound, 0302 clinical medicine, Ischemia, medicine, Animals, Myocytes, Cardiac, Phosphorylation, lcsh:QH573-671, Mice, Knockout, Cell Death, Mitochondrial Permeability Transition Pore, lcsh:Cytology, MPTP, Cell Biology, medicine.disease, Mitochondria, Cell biology, [SDV] Life Sciences [q-bio], Mice, Inbred C57BL, Myocardial infarction, 030104 developmental biology, Mitochondrial permeability transition pore, chemistry, Reperfusion Injury, Mitochondrial Membranes, Reperfusion, Reperfusion injury, Cyclophilin D, Signal Transduction
Abstract: The mitochondrial permeability transition pore (mPTP) plays a critical role in the pathogenesis of cardiovascular diseases, including ischemia/reperfusion injury. Although the pore structure is still unresolved, the mechanism through which cyclophilin D (CypD) regulates mPTP opening is the subject of intensive studies. While post-translational modifications of CypD have been shown to modulate pore opening, specific phosphorylation sites of CypD have not yet been identified. We hypothesized here that phosphorylation of CypD on a serine residue controls mPTP opening and subsequent cell death at reperfusion. We combined in silico analysis with in vitro and genetic manipulations to determine potential CypD phosphorylation sites and their effect on mitochondrial function and cell death. Importantly, we developed an in vivo intramyocardial adenoviral strategy to assess the effect of the CypD phosphorylation event on infarct size. Our results show that although CypD can potentially be phosphorylated at multiple serine residues, only the phosphorylation status at S191 directly impacts the ability of CypD to regulate the mPTP. Protein-protein interaction strategies showed that the interaction between CypD and oligomycin sensitivity-conferring protein (OSCP) was reduced by 45% in the phosphoresistant S191A mutant, whereas it was increased by 48% in the phosphomimetic S191E mutant cells. As a result, the phosphoresistant CypD S191A mutant was protected against 18 h starvation whereas cell death was significantly increased in phosphomimetic S191E group, associated with mitochondrial respiration alteration and ROS production. As in vivo proof of concept, in S191A phosphoresistant rescued CypD-KO mice developed significantly smaller infarct as compared to WT whereas infarct size was drastically increased in S191E phosphomimetic rescued mice. We conclude that CypD phosphorylation at S191 residue leads to its binding to OSCP and thus sensitizes mPTP opening for the subsequent cell death.
Published: 2020

31. Cemented vs Uncemented Femoral Components: A Randomized, Controlled Trial at 10 Years Minimum Follow-Up

Author: Elvire Servien, Guillaume Demey, Yves Malemo, Sébastien Lustig, Raymond Kenney, 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), Laboratoire de Biomécanique et Mécanique des Chocs (LBMC UMR T9406 ), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Gustave Eiffel
Subjects: Reoperation, musculoskeletal diseases, medicine.medical_specialty, Knee Joint, SURVIVAL RATE, Total knee arthroplasty, Osteoarthritis, Prosthesis Design, law.invention, TOTAL KNEE ARTHROPLASTY, 03 medical and health sciences, 0302 clinical medicine, CEMENTED FEMORAL IMPLANT, UNCEMENTED FEMORAL IMPLANT, Randomized controlled trial, law, Survivorship curve, Humans, Medicine, Orthopedics and Sports Medicine, Arthroplasty, Replacement, Knee, 10. No inequality, Survival rate, Aged, Fixation (histology), Aged, 80 and over, 030222 orthopedics, business.industry, Bone Cements, [SPI.MECA.BIOM]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], LOOSENING, Middle Aged, musculoskeletal system, medicine.disease, Prosthesis Failure, 3. Good health, Surgery, Treatment Outcome, surgical procedures, operative, Radiological weapon, Implant, Knee Prosthesis, business, Follow-Up Studies
Abstract: Background The type of total knee arthroplasty (TKA) fixation (cemented or uncemented) is still subject to debate. The aim of this study is to assess the survival rate, clinical outcomes, and radiological results of TKA according to the fixation type. Methods A total of 130 patients were randomly assigned to either the cement group (cemented femoral and tibial implants) or the hybrid group (cemented tibial implant, uncemented femoral implant). The inclusion criteria were patients between 50 and 90 years old who underwent primary TKA for osteoarthritis between 2004 and 2005 without a history of open knee surgery. Revisions and complications were reported, as well as clinical scores and radiological signs of loosening. Results One hundred eighteen patients had complete data at 10 years of minimum follow-up (59 in each group). The mean age was 72 years old. The mean follow-up was 13 years. The survival rate was 98% at 13 years in both groups (1 aseptic loosening at 2 years in the cement group, 1 septic loosening in the hybrid group). The complication rate in the cement group was 8.5% (n = 5) vs 12.1% (n = 7) in the hybrid group (P = .8). The clinical results were not significantly different. In the cement group, 25% of patients (n = 15) had radiolucent lines at 10 years. In the hybrid group, 33% of patients had bone transparencies, not evolving or symptomatic. Conclusion At a minimum follow-up of 10 years, there were no significant differences between cemented TKA and hybrid TKA for the survivorship, the complication rate, the clinical scores, or the radiological signs of loosening. Level of Evidence I.
Published: 2020

32. Urinary Sodium-to-Potassium Ratio and Blood Pressure in CKD

Author: Natalia Alencar de Pinho, Jean Kaboré, Maurice Laville, Marie Metzger, Céline Lange, Christian Jacquelinet, Christian Combe, Denis Fouque, Luc Frimat, Carol Ayav, Bruce M. Robinson, Tilman Drueke, Ziad A. Massy, Bénédicte Stengel, Thierry Hannedouche, Bruno Moulin, Sébastien Mailliez, Gaétan Lebrun, Eric Magnant, Gabriel Choukroun, Benjamin Deroure, Adeline Lacraz, Guy Lambrey, Jean Philippe Bourdenx, Marie Essig, Thierry Lobbedez, Raymond Azar, Hacène Sekhri, Mustafa Smati, Mohamed Jamali, Alexandre Klein, Michel Delahousse, Séverine Martin, Isabelle Landru, Eric Thervet, Philippe Lang, Xavier Belenfant, Pablo Urena, Carlos Vela, Dominique Chauveau, Viktor Panescu, Christian Noel, François Glowacki, Maxime Hoffmann, Maryvonne Hourmant, Dominique Besnier, Angelo Testa, François Kuentz, Philippe Zaoui, Charles Chazot, Laurent Juillard, Stéphane Burtey, Adrien Keller, Nassim Kamar, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut de Recherche en Sciences de la Santé (IRSS), CNRST, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Agence de la biomédecine [Saint-Denis la Plaine], Service de Néphrologie Transplantation, Dialyse et Aphérèse [CHU Bordeaux], CHU Bordeaux [Bordeaux], Bioingénierie tissulaire (BIOTIS), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Arbor Research Collaborative for Health, Hôpital Ambroise Paré [AP-HP], 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), Agence Nationale de la Recherche, ANR Agence Nationale de la Recherche, ANR, The CKD-REIN study is funded by the Agence Nationale de la Recherche through the 2010 «Cohortes-Investissements d’Avenir » program (ANR) and by the 2010 national Programme Hospitalier de Recherche Clinique . CKD-REIN is also supported through a public–private partnership with Amgen , Fresenius Medical Care , and GlaxoSmithKline (GSK) since 2012, Lilly France since 2013, Otsuka Pharmaceutical since 2015, Baxter and Merck Sharp & Dohme-Chibret (MSD France) from 2012 to 2017, Sanofi-Genzyme from 2012 to 2015, and Vifor Fresenius and AstraZeneca , since 2018. Inserm Transfert set up and has managed this partnership since 2011., Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Chronic Kidney Disease - Réseau Epidémiologie et Information en Néphrologie (CKD REIN), and Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: medicine.medical_specialty, Urinary system, Population, 030232 urology & nephrology, 030204 cardiovascular system & hematology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Gastroenterology, Excretion, 03 medical and health sciences, 0302 clinical medicine, Clinical Research, Interquartile range, Internal medicine, medicine, salt, 10. No inequality, education, sodium, education.field_of_study, business.industry, potassium, blood pressure, medicine.disease, 3. Good health, Blood pressure, Quartile, Nephrology, Albuminuria, medicine.symptom, business, chronic kidney disease, Kidney disease
Abstract: Introduction In the general population, urinary sodium-to-potassium (uNa/K) ratio associates more strongly with high blood pressure (BP) than either urinary sodium or potassium alone. Whether this is also the case among patients with chronic kidney disease (CKD) is unknown. Methods We studied the associations of spot urine sodium-to-creatinine (uNa/Cr), potassium-to-creatinine (uK/Cr), and uNa/K ratios with a single office BP reading in 1660 patients with moderate to severe CKD at inclusion in the CKD-REIN cohort. Results Patients' median age was 68 (interquartile range [IQR], 59–76) years; most were men (65%), had moderate CKD (57%), and albuminuria (72%). Mean systolic and diastolic BP was 142/78 mm Hg. Spot uNa/Cr and uNa/K ratios were positively associated with systolic, mean arterial, and pulse pressures. The mean adjusted difference in systolic BP between the highest and the lowest quartile (Q4 vs. Q1) was 4.24 (95% confidence interval [CI], 1.53–6.96) mm Hg for uNa/Cr and 4.79 (95% CI, 2.18–7.39) mm Hg for uNa/K. Quartiles of spot uK/Cr were not associated with any BP index. The higher the quartile of uNa/K, the higher the prevalence ratio of uncontrolled (Q4 vs. Q1, 1.43; 95% CI, 1.19–1.72) or apparently treatment-resistant hypertension (Q4 vs. Q1, 1.35; 95% CI, 1.14–1.60). Findings were consistent in a subset of 803 individuals with 2 BP readings. Conclusion In patients with CKD, higher urinary sodium excretion is associated with higher BP, but unlike in general population, lower potassium excretion is not. Urinary Na/K does not add significant value in assessing high BP risk, except perhaps for hypertension control assessment., Graphical abstract
Published: 2020

33. ERRα Expression in Bone Metastases Leads to an Exacerbated Antitumor Immune Response

Author: Soumaya El-Moghrabi, Martine Duterque-Coquillaud, Alexandra Lainé, Philippe Clézardin, Sandra Geraci, Cyril Boyault, Casina W.S. Kan, Emmanuelle Meugnier, Lamia Bouazza, Julien C. Marie, Yuji Yoshiko, Hector Hernandez-Vargas, Edith Bonnelye, Mathilde Proponnet-Guerault, Claire Benetollo, Mathilde Bouchet, Inflammasome NLRP3 – NLRP3 Inflammasome, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre 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), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Régulations métaboliques, nutrition et diabètes (RMND), 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), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Institut de biologie de Lille - UMS 3702 (IBL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), ANR-10-LABX-0061,DEVWECAN,Development Cancer and Targeted Therapies(2010), Institut de Génomique Fonctionnelle de Lyon (IGFL), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), 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 Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), 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), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Centre de recherche en neurosciences de Lyon (CRNL), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Inserm UMR1069, Nutrition, croissance et cancer (U 1069) (N2C), 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), Université de Lille-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS), Médecine cellulaire et moléculaire (MCM), Université de Lille, Sciences et Technologies-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, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon], Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Bonnelye, Edith, Development Cancer and Targeted Therapies - - DEVWECAN2010 - ANR-10-LABX-0061 - LABX - VALID, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Cardiovasculaire, métabolisme, diabétologie et nutrition [CarMeN], Institut de biologie de Lille - UMS 3702 [IBL], Médecine cellulaire et moléculaire [MCM], Institut National de la Santé et de la Recherche Médicale [INSERM], Institut de Génomique Fonctionnelle de Lyon [IGFL], Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) [IAB], Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases [LYOS], and Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Subjects: 0301 basic medicine, Cancer Research, Chemokine, T-Lymphocytes, [SDV]Life Sciences [q-bio], Apoptosis, Mice, 0302 clinical medicine, Tumor Cells, Cultured, Tumor Microenvironment, Cytotoxic T cell, ComputingMilieux_MISCELLANEOUS, Mice, Inbred BALB C, biology, Prognosis, Primary tumor, 3. Good health, Gene Expression Regulation, Neoplastic, Receptors, Estrogen, Oncology, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Signal Transduction, [SDV.IMM] Life Sciences [q-bio]/Immunology, Mice, Nude, Bone Neoplasms, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, 03 medical and health sciences, Transforming Growth Factor beta3, Breast cancer, Immune system, [SDV.CAN] Life Sciences [q-bio]/Cancer, Biomarkers, Tumor, medicine, Animals, Humans, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Cell Proliferation, Chemokine CCL20, business.industry, medicine.disease, Xenograft Model Antitumor Assays, CCL20, 030104 developmental biology, Transforming growth factor, beta 3, biology.protein, Cancer research, Chemokine CCL17, business, Transforming growth factor
Abstract: Bone is the most common metastatic site for breast cancer. Although the estrogen-related receptor alpha (ERRα) has been implicated in breast cancer cell dissemination to the bone from the primary tumor, its role after tumor cell anchorage in the bone microenvironment remains elusive. Here, we reveal that ERRα inhibits the progression of bone metastases of breast cancer cells by increasing the immune activity of the bone microenvironment. Overexpression of ERRα in breast cancer bone metastases induced expression of chemokines CCL17 and CCL20 and repressed production of TGFβ3. Subsequently, CD8+ T lymphocytes recruited to bone metastases escaped TGFβ signaling control and were endowed with exacerbated cytotoxic features, resulting in significant reduction in metastases. The clinical relevance of our findings in mice was confirmed in over 240 patients with breast cancer. Thus, this study reveals that ERRα regulates immune properties in the bone microenvironment that contributes to decreasing metastatic growth. Significance: This study places ERRα at the interplay between the immune response and bone metastases of breast cancer, highlighting a potential target for intervention in advanced disease.
Published: 2020

34. Plant-based diets to manage the risks and complications of chronic kidney disease

Author: Catherine M. Clase, Stephan J. L. Bakker, Karine Moreau, Siren Sezer, Adamasco Cupisti, Adrian Post, Denis Fouque, Carla Maria Avesani, Giorgina Barbara Piccoli, Pablo Molina, Ángeles Espinosa-Cuevas, Philippe Chauveau, Juan Jesus Carrero, Ailema González-Ortiz, Vincenzo Bellizzi, Department of Internal Medicine, Huntsman Cancer Institute, University of Groningen, Institut de Recherche en Génie Civil et Mécanique (GeM), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), and Institut National des Sciences Appliquées (INSA)-Université de Lyon-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)
Subjects: Dietary Fiber, 0301 basic medicine, POTASSIUM EXCRETION, Acid-Base Equilibrium, Diet, Healthy, Diet, Mediterranean, Dietary Approaches To Stop Hypertension, Dietary Fats, Unsaturated, Disease Progression, Humans, Hyperkalemia, Phosphorus, Dietary, Plant Proteins, Dietary, Potassium, Dietary, Renal Dialysis, Renal Insufficiency, Chronic, Diet, Vegetarian, Mediterranean diet, [SDV]Life Sciences [q-bio], medicine.medical_treatment, 030232 urology & nephrology, Mediterranean, Gut flora, GLOMERULAR-FILTRATION-RATE, LOW-PROTEIN-DIET, 0302 clinical medicine, Renal Insufficiency, Chronic, ALL-CAUSE MORTALITY, Plant Proteins, 2. Zero hunger, Unsaturated, biology, food and beverages, Phosphorus, 3. Good health, MEDITERRANEAN DIET, CHAIN FATTY-ACIDS, Nephrology, Water-Soluble Vitamin, medicine.medical_specialty, METABOLIC-ACIDOSIS, Dietary, MOLECULAR-WEIGHT PROTEINS, 03 medical and health sciences, Vegetarian, Low-protein diet, medicine, CARDIOVASCULAR EVENTS, Intensive care medicine, Dialysis, Healthy, business.industry, Metabolic acidosis, medicine.disease, biology.organism_classification, Dietary Fats, Diet, WATER-SOLUBLE VITAMINS, Malnutrition, 030104 developmental biology, Potassium, business, Kidney disease
Abstract: Traditional dietary recommendations for patients with chronic kidney disease (CKD) focus on the quantity of nutrients consumed. Without appropriate dietary counselling, these restrictions can result in a low intake of fruits and vegetables and a lack of diversity in the diet. Plant nutrients and plant-based diets could have beneficial effects in patients with CKD: increased fibre intake shifts the gut microbiota towards reduced production of uraemic toxins; plant fats, particularly olive oil, have anti-atherogenic effects; plant anions might mitigate metabolic acidosis and slow CKD progression; and as plant phosphorus has a lower bioavailability than animal phosphorus, plant-based diets might enable better control of hyperphosphataemia. Current evidence suggests that promoting the adoption of plant-based diets has few risks but potential benefits for the primary prevention of CKD, as well as for delaying progression in patients with CKD G3-5. These diets might also help to manage and prevent some of the symptoms and metabolic complications of CKD. We suggest that restriction of plant foods as a strategy to prevent hyperkalaemia or undernutrition should be individualized to avoid depriving patients with CKD of these potential beneficial effects of plant-based diets. However, research is needed to address knowledge gaps, particularly regarding the relevance and extent of diet-induced hyperkalaemia in patients undergoing dialysis. Emerging evidence suggests that plant-based diets could help to prevent chronic kidney disease (CKD), manage its symptoms and metabolic complications and delay disease progression. Here, the authors discuss the potential risks and benefits of these diets in patients with CKD, as well as implementation strategies and knowledge gaps.
Published: 2020

35. Clinical and virological data of the first cases of COVID-19 in Europe: a case series

Author: Bruno Lina, M. Valette, Paul-Henri Wicky, Lila Bouadma, Alexandre Gaymard, Duc Bao Nguyen, Alexandra Mailles, Flora Donati, Quentin Le Hingrat, Xavier Duval, Yazdan Yazdanpanah, Marion Parisey, Denis Malvy, Jean-François Timsit, Nadhira Houhou-Fidouh, Sylvie Behillil, Diane Descamps, François-Xavier Lescure, Vincent Enouf, Jean-Christophe Lucet, M. Bouscambert-Duchamp, Sylvie van-der-Werf, Services de Maladies Infectieuses et Tropicales [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Réanimation médicale et infectieuse - Medical and Infectious Diseases Intensive Care [Paris], Department of Infectious Diseases and Tropical Medicine [Bordeaux], CHU Bordeaux [Bordeaux], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Institut Pasteur [Paris] (IP), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Laboratoire de Virologie [Lyon], Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Virpath-Grippe, de l'émergence au contrôle -- Virpath-Influenza, from emergence to control (Virpath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Virologie [CHU Bichat], 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), Plateforme de Microbiologie Mutualisée (PIBnet) - Mutualized Platform for Microbiology (P2M), Pasteur International Bioresources network (PIBNet), Santé publique France - French National Public Health Agency [Saint-Maurice, France], Infection Control Unit [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Department of Epidemiology, Biostatistics and Clinical Research [Paris], CIC Hôpital Bichat, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-UFR de Médecine, REACTing (Research & Action Emerging Infectious Diseases)., ANR-20-COVI-0035,COCONEL,COronavirus et CONfinement : Enquête Longitudinale(2020), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR), Institut Pasteur [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-UFR de Médecine-AP-HP - Hôpital Bichat - Claude Bernard [Paris], École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and CCSD, Accord Elsevier
Subjects: Adult, Male, 0301 basic medicine, China, Pediatrics, medicine.medical_specialty, Pneumonia, Viral, Disease, Urine, medicine.disease_cause, Virus, IDLIC, Betacoronavirus, Feces, 03 medical and health sciences, 0302 clinical medicine, Nasopharynx, Pandemic, medicine, Humans, Infection control, 030212 general & internal medicine, Pandemics, Coronavirus, Aged, 80 and over, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Travel, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, SARS-CoV-2, business.industry, COVID-19, Middle Aged, Viral Load, medicine.disease, 3. Good health, Natural history, Pneumonia, Blood, 030104 developmental biology, Infectious Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, RNA, Viral, Female, France, Coronavirus Infections, business, Viral load
Abstract: International audience; BACKGROUND:On Dec 31, 2019, China reported a cluster of cases of pneumonia in people at Wuhan, Hubei Province. The responsible pathogen is a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report the relevant features of the first cases in Europe of confirmed infection, named coronavirus disease 2019 (COVID-19), with the first patient diagnosed with the disease on Jan 24, 2020.METHODS:In this case series, we followed five patients admitted to Bichat-Claude Bernard University Hospital (Paris, France) and Pellegrin University Hospital (Bordeaux, France) and diagnosed with COVID-19 by semi-quantitative RT-PCR on nasopharyngeal swabs. We assessed patterns of clinical disease and viral load from different samples (nasopharyngeal and blood, urine, and stool samples), which were obtained once daily for 3 days from hospital admission, and once every 2 or 3 days until patient discharge. All samples were refrigerated and shipped to laboratories in the National Reference Center for Respiratory Viruses (The Institut Pasteur, Paris, and Hospices Civils de Lyon, Lyon, France), where RNA extraction, real-time RT-PCR, and virus isolation and titration procedures were done.FINDINGS:The patients were three men (aged 31 years, 48 years, and 80 years) and two women (aged 30 years and 46 years), all of Chinese origin, who had travelled to France from China around mid-January, 2020. Three different clinical evolutions are described: (1) two paucisymptomatic women diagnosed within a day of exhibiting symptoms, with high nasopharyngeal titres of SARS-CoV-2 within the first 24 h of the illness onset (5·2 and 7·4 log10 copies per 1000 cells, respectively) and viral RNA detection in stools; (2) a two-step disease progression in two young men, with a secondary worsening around 10 days after disease onset despite a decreasing viral load in nasopharyngeal samples; and (3) an 80-year-old man with a rapid evolution towards multiple organ failure and a persistent high viral load in lower and upper respiratory tract with systemic virus dissemination and virus detection in plasma. The 80-year-old patient died on day 14 of illness (Feb 14, 2020); all other patients had recovered and been discharged by Feb 19, 2020.INTERPRETATION:We illustrated three different clinical and biological types of evolution in five patients infected with SARS-CoV-2 with detailed and comprehensive viral sampling strategy. We believe that these findings will contribute to a better understanding of the natural history of the disease and will contribute to advances in the implementation of more efficient infection control strategies.
Published: 2020

36. Lung and chest wall mechanics in patients with acute respiratory distress syndrome, expiratory flow limitation, and airway closure

Author: Loredana Baboi, Emanuele Turbil, Bruno Louis, Louis-Marie Galerneau, Martin Cour, Nicolas Terzi, Mehdi Mezidi, Claude Guérin, Louis Kreitmann, Laurent Argaud, Hodane Yonis, STMicroelectronics [Crolles] (ST-CROLLES), Unité de soins intensifs médicaux [CHU Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Hôpital Edouard Herriot, Service Anesthésie Réanimation, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), THALES Airborne Systems [Elancourt], and THALES
Subjects: ARDS, medicine.medical_specialty, Supine position, Physiology, [SDV]Life Sciences [q-bio], medicine.medical_treatment, 03 medical and health sciences, 0302 clinical medicine, Physiology (medical), Internal medicine, medicine, Humans, Prospective Studies, Expiration, Thoracic Wall, Lung, Positive end-expiratory pressure, Mechanical ventilation, Respiratory Distress Syndrome, expiratory flow limitation, business.industry, Exhalation, 030208 emergency & critical care medicine, acute respiratory distress syndrome, respiratory system, medicine.disease, medicine.anatomical_structure, 030228 respiratory system, airway closure, Respiratory Mechanics, Cardiology, business, Airway, positive end-expiratory pressure
Abstract: Tidal expiratory flow limitation (EFL), which may herald airway closure (AC), is a mechanism of loss of aeration in ARDS. In this prospective, short-term, two-center study, we measured static and dynamic chest wall (Est,cw and Edyn,cw) and lung (Est,L and Edyn,L) elastance with esophageal pressure, EFL, and AC at 5 cmH(2)O positive end-expiratory pressure (PEEP) in intubated, sedated, and paralyzed ARDS patients. For EFL determination, we used the atmospheric method and a new device allowing comparison of tidal flow during expiration to PEEP and to atmosphere. AC was validated when airway opening pressure (AOP) assessed from volume-pressure curve was found greater than PEEP by at least 1 cmH(2)O. EFL was defined whenever flow did not increase between exhalation to PEEP and to atmosphere over all or part of expiration. Elastance values were expressed as percentage of normal predicted values (%N). Among the 25 patients included, eight had EFL (32%) and 13 AOP (52%). Between patients with and without EFL Edyn,cw [median (1st to 3rd quartiles)] was 70 (16-127) and 102 (70-142) %N (P = 0.32) and Edyn,L338 (332-763) and 224 (160-275) %N (P \textless 0.001). The corresponding values for Est,cw and Est,L were 70 (56-88) and 85 (64-103) %N (P = 0.35) and 248 (206-348) and 170 (144-195) (P = 0.02), respectively. Dynamic E(L) had an area receiver operating characteristic curve of 0.88 [95% confidence intervals 0.83-0.92] for EFL and 0.74[0.68-0.79] for AOP. Higher Edyn,L was accurate to predict EFL in ARDS patients; AC can occur independently of EFL, and both should be assessed concurrently in ARDS patients.NEW & NOTEWORTHY Expiratory flow limitation (EFL) and airway closure (AC) were observed in 32% and 52%, respectively, of 25 patients with ARDS investigated during mechanical ventilation in supine position with a positive end-expiratory pressure of 5 cmH(2)O. The performance of dynamic lung elastance to detect expiratory flow limitation was good and better than that to detect airway closure. The vast majority of patients with EFL also had AC; however, AC can occur in the absence of EFL.
Published: 2020

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

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

38. Perceived Health and Quality of Life in Patients With CKD, Including Those With Kidney Failure: Findings From National Surveys in France

Author: Elodie Speyer, Denis Fouque, Stéphane Edet, Carole Ayav, Anne Durand, Ziad A. Massy, Karine Legrand, Bénédicte Stengel, Maurice Laville, Serge Briançon, Luc Frimat, Christian Combe, Stéphanie Gentile, Christian Jacquelinet, Willy Ngueyon Sime, Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service Néphrologie/Dialyse [AP-HP Ambroise-Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Bioingénierie tissulaire (BIOTIS), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), CHU Rouen, Normandie Université (NU), Centre d'Epidémiologie Clinique (CIC-EC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie [Ambroise Paré], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Ambroise Paré, 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), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, dialysis patients, symptom burden, patient well-being, medicine.medical_treatment, 030232 urology & nephrology, health status, Chronic kidney disease (CKD), survey data, Random Allocation, 0302 clinical medicine, Quality of life, kidney transplant patients, Outcome Assessment, Health Care, Medicine, Registries, 030212 general & internal medicine, education.field_of_study, Minimal clinically important difference, Middle Aged, 3. Good health, Renal Replacement Therapy, Nephrology, Female, health-related quality of life (HRQoL), France, Glomerular Filtration Rate, medicine.medical_specialty, Population, Renal function, patient-reported outcomes (PROs), Diagnostic Self Evaluation, 03 medical and health sciences, Internal medicine, Diabetes mellitus, Humans, Renal Insufficiency, Chronic, education, Dialysis, business.industry, medicine.disease, Kidney Transplantation, Obesity, kidney failure, Cross-Sectional Studies, renal replacement therapy (RRT), end-stage renal disease (ESRD), Quality of Life, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Kidney disease
Abstract: International audience; RATIONALE & OBJECTIVE: Health-related quality of life (HRQoL) is a major outcome measure increasingly used in patients with chronic kidney disease (CKD). We evaluated the association between different stages of CKD and the physical and mental health domains of HRQoL.STUDY DESIGN: Cross-sectional study.SETTING & PARTICIPANTS: 2,693 outpatients with moderate (stage 3, estimated glomerular filtration rate [eGFR], 30-60mL/min/1.73m2) or advanced (stages 4-5, estimated glomerular filtration rate40% of those with advanced CKD or receiving dialysis, 12% with a functioning transplant, and 3% of the general population sample. HRQoL physical scores (adjusted for age, sex, education, obesity, and diabetes) were significantly lower in patients in all CKD subgroups than in the general population. For patients receiving dialysis, the magnitude of the difference in physical score versus the general population exceeded 4.5 points, the minimal clinically important difference for this score in this study; for both kidney transplant recipients and patients with advanced CKD, the magnitude of the difference was close to this threshold. For mental score, only dialysis patients had a score that differed from that of the general population by more than the minimal clinically important difference.LIMITATIONS: Cross-sectional study design for each subpopulation.CONCLUSIONS: This study highlights the degree to which perceived physical health is lower in the setting of CKD than in the general population, even in the absence of kidney failure, and calls for greater attention to CKD-related quality of life.
Published: 2020

39. Nomenclature for kidney function and disease: report of a Kidney Disease

Author: Caroline Vinck, Andrew S. Levey, Mark Lambie, Josephine P. Briggs, Andrew Davenport, Susan J. Allison, Stacy L. Christiansen, Shari E. Leventhal, Stephen B. Walsh, Joseph Laycock, Jonathan S. Bromberg, Paul M. Palevsky, Denis Fouque, Brenda R. Hemmelgarn, Jennifer St. Clair Russell, Lesley A. Inker, Pascale H. Lane, Michael Cheung, Rajnish Mehrotra, Detlef Bockenhauer, Adeera Levin, Matthias Kretzler, Mark A. Perazella, Ron T. Gansevoort, Kai-Uwe Eckardt, Lesley Rees, Daniel E. Weiner, John S. Gill, Harold I. Feldman, Julie R. Ingelfinger, Allison Tong, Michael Mittelman, Michel Jadoul, Pierre Ronco, Nijsje M. Dorman, Marlies Ostermann, Patricia Morrissey, Wolfgang C. Winkelmayer, Franz Schaefer, Eddie L. Greene, Ewout J. Hoorn, School of Metallurgy and Materials, University of Birmingham [Birmingham], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), California Institute of Technology (CALTECH), Service de Néphrologie et Dialyses [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - (SLuc) Service de néphrologie, Cardiovascular Centre (CVC), Groningen Kidney Center (GKC), and Internal Medicine
Subjects: 0301 basic medicine, medicine.medical_specialty, Glossary, kidney disease, precision medicine, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Renal function, Disease, Q1, 03 medical and health sciences, 0302 clinical medicine, kidney measures, medicine, patient-centeredness, Intensive care medicine, kidney function, Kidney, acute kidney diseases and disorders, business.industry, urogenital system, Acute kidney injury, Precision medicine, medicine.disease, R1, 3. Good health, kidney failure, 030104 developmental biology, medicine.anatomical_structure, acute kidney injury, Nephrology, Albuminuria, nomenclature, medicine.symptom, business, chronic kidney disease, Kidney disease
Abstract: The worldwide burden of kidney disease is rising, but public awareness remains limited, underscoring the need for more effective communication by stakeholders in the kidney health community. Despite this need for clarity, the nomenclature for describing kidney function and disease lacks uniformity. In June 2019, Kidney Disease: Improving Global Outcomes (KDIGO) convened a Consensus Conference with the goal of standardizing and refining the nomenclature used in the English language to describe kidney function and disease, and of developing a glossary that could be used in scientific publications. Guiding principles of the conference were that the revised nomenclature should be patient-centered, precise, and consistent with nomenclature used in the KDIGO guidelines. Conference attendees reached general consensus on the following recommendations: (i) to use "kidney" rather than "renal" or "nephro-" when referring to kidney disease and kidney function; (ii) to use "kidney failure" with appropriate descriptions of presence or absence of symptoms, signs, and treatment, rather than "end-stage kidney disease"; (iii) to use the KDIGO definition and classification of acute kidney diseases and disorders (AKD) and acute kidney injury (AKI), rather than alternative descriptions, to define and classify severity of AKD and AKI; (iv) to use the KDIGO definition and classification of chronic kidney disease (CKD) rather than alternative descriptions to define and classify severity of CKD; and (v) to use specific kidney measures, such as albuminuria or decreased glomerular filtration rate (GFR), rather than "abnormal" or "reduced" kidney function to describe alterations in kidney structure and function. A proposed 5-part glossary contains specific items for which there was general agreement. Conference attendees acknowledged limitations of the recommendations and glossary, but they considered standardization of scientific nomenclature to be essential for improving communication.
Published: 2020

40. A non-human primate model of stroke reproducing endovascular thrombectomy and allowing long-term imaging and neurological read-outs

Author: F. Taborik, Karine Portier, Norbert Nighoghossian, Adrien Oudotte, Michaël Verset, Thomas Troalen, Omer Eker, Denis Vivien, Inés Mérida, Christelle Leon, Christian Tourvieille, Didier Le Bars, Emmanuelle Canet-Soulas, Michel Ovize, Hugues Contamin, Nicolas Costes, Nikolaos Makris, Véronique Agin, Joachim Confais, Tae-Hee Cho, Mohamed Aggour, Sophie Lancelot, Justine Debatisse, Jean-Baptiste Langlois, Océane Wateau, Marjorie Villien, Imagerie Tomographique et Radiothérapie, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-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 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)-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), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Laboratoire d'Ecologie des Hydrosystèmes Naturels et Anthropisés (LEHNA), Université de Lyon-Université de Lyon-École Nationale des Travaux Publics de l'État (ENTPE)-Centre National de la Recherche Scientifique (CNRS), Cynbiose, CYNBIOSE, Institut Claude Bourgelat (ICLB), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Siemens Healthcare [France], Siemens AG [Munich], Institute of Electronic Structure and Laser (FORTH-IESL), Foundation for Research and Technology - Hellas (FORTH), Radiopharmaceutical and Neurochemical Biomarkers Team (BioRaN), Centre de recherche en neurosciences de Lyon (CRNL), 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)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Cardiology, Hospices Civils de Lyon (HCL), Laboratoire de Chimie de la Matière Condensée de Paris (site ENSCP) (LCMCP (site ENSCP)), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC), French Ministry of Higher Education and Research (ANRT), ANR-15-CE17-0020,CYCLOPS,CYCLOsporine A : effet neuroprotecteur dans un modèle Primate de Stroke en imagerie(2015), ANR-16-RHUS-0009,MARVELOUS,MARVELOUS(2016), 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-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), 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), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, [SDV]Life Sciences [q-bio], Executive Function, 0302 clinical medicine, Occlusion, Stroke, Thrombectomy, 0303 health sciences, Behavior, Animal, Endovascular Procedures, Infarction, Middle Cerebral Artery, Magnetic Resonance Imaging, 3. Good health, Treatment Outcome, Neurology, Blood-Brain Barrier, Motor Skills, Reperfusion Injury, Middle cerebral artery, Cardiology, medicine.symptom, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, Ischemia, Context (language use), ischemia–reperfusion, Asymptomatic, Lesion, 03 medical and health sciences, medicine.artery, Internal medicine, medicine, Animals, cardiovascular diseases, Thrombus, Ischemic Stroke, 030304 developmental biology, business.industry, Original Articles, medicine.disease, Disease Models, Animal, Macaca fascicularis, Endovascular non-human primate stroke model, PET-MRI imaging, Positron-Emission Tomography, neurofunctional tests, Neurology (clinical), Tomography, X-Ray Computed, business, 030217 neurology & neurosurgery
Abstract: International audience; Stroke is a devastating disease. Endovascular mechanical thrombectomy is dramatically changing the management of acute ischemic stroke, raising new challenges regarding brain outcome and opening up new avenues for brain protection. In this context, relevant experiment models are required for testing new therapies and addressing important questions about infarct progression despite successful recanalization, reversibility of ischemic lesions, blood-brain barrier disruption and reperfusion damage. Here, we developed a minimally invasive non-human primate model of cerebral ischemia (Macaca fascicularis) based on an endovascular transient occlusion and recanalization of the middle cerebral artery (MCA). We evaluated per-occlusion and post-recanalization impairment on PET-MRI, in addition to acute and chronic neuro-functional assessment. Voxel-based analyses between per-occlusion PET-MRI and day-7 MRI showed two different patterns of lesion evolution: "symptomatic salvaged tissue" (SST) and "asymptomatic infarcted tissue" (AIT). Extended SST was present in all cases. AIT, remote from the area at risk, represented 45% of the final lesion. This model also expresses both worsening of fine motor skills and dysexecutive behavior over the chronic post-stroke period, a result in agreement with cortical-subcortical lesions. We thus fully characterized an original translational model of ischemia-reperfusion damage after stroke, with consistent ischemia time, and thrombus retrieval for effective recanalization.
Published: 2020

41. Evolution of renal function in patients with severe intestinal failure on home parenteral nutrition

Author: Laetitia Koppe, M. Lauverjat, Cécile Chambrier, D. Barnoud, Denis Fouque, E. Chalencon, Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hospices Civils de LyonUniversity of Lyon, and ROSSI, Sabine
Subjects: measured glomerular filtration rate, medicine.medical_specialty, 030309 nutrition & dietetics, Population, 030232 urology & nephrology, Urology, Renal function, urologic and male genital diseases, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, home parenteral nutrition, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, chronic renal failure, intestinal failure, Epidemiology, medicine, AcademicSubjects/MED00340, education, 0303 health sciences, Transplantation, education.field_of_study, Creatinine, business.industry, Gold standard, Original Articles, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Parenteral nutrition, chemistry, Nephrology, Complication, business, Kidney disease
Abstract: Background Kidney disease is a frequent but underestimated complication in patients suffering from intestinal failure (IF) treated by long-term home parenteral nutrition (HPN). The evolution in glomerular filtration rate (GFR) over time is poorly characterized. The current equations for estimating GFR have limited precision. No study has specifically investigated the reliability of recent creatinine-based estimated GFR (eGFR) equations in this population. The aim of this study was to evaluate the renal function decline under home parenteral nutrition (HPN) with a gold standard method and compare the performances of routinely used eGFR equations. Methods Forty patients with HPN and two or more GFR measurements were retrospectively studied. The renal function decline was calculated by the slope drawn between the successive measured GFRs (mGFRs). The performances of the Modification of Diet in Renal Disease, Chronic Kidney Disease Epidemiology Collaboration, full age spectrum and revised Lund–Malmö equations were compared with reference methods (inulin or iohexol clearance). Results The mean mGFR was 78 ± 28 mL/min/1.73 m2. The annual decline of mGFR was −1.9 mL/min/1.73 m2/year. No predisposing factor was identified to predict impairment in renal function. eGFR formulas grossly overestimated mGFR and had a low level of accuracy. Conclusions Patients with IF are at significant risk for impaired renal function. In this population, the tested eGFR equations were inaccurate. However, monitoring kidney function with mGFR remains important in these patients, as their GFR regularly declines and no specific risk factor has yet been identified.
Published: 2020

42. Liver transplantation as a rescue therapy for severe neurologic forms of Wilson disease

Author: Aurélia Poujois, Rodolphe Sobesky, Wassilios G. Meissner, Anne-Sophie Brunet, Emmanuel Broussolle, Chloé Laurencin, Laurence Lion-François, Olivier Guillaud, Alain Lachaux, François Maillot, Jérémie Belin, Ephrem Salamé, Claire Vanlemmens, Bruno Heyd, Céline Bellesme, Dalila Habes, Christophe Bureau, Fabienne Ory-Magne, Pascal Chaine, Jean-Marc Trocello, Daniel Cherqui, Didier Samuel, Victor de Ledinghen, Jean-Charles Duclos-Vallée, France Woimant, National reference Centre for Wilson's Disease [Paris] (CRMR Wilson), Service de neurologie [Univ. Paris VII], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service d'Electroneuromyographie et Service de Neurologie C [Hôpital Pierre Wertheimer - HCL], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Université de Lyon, Département d'hépatologie, Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Groupe de Recherche en Economie Théorique et Appliquée (GREThA), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Hôpital Claude Huriez [Lille], CHU Lille, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Badji Mokhtar de Annaba, CHU Toulouse [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Paul Brousse, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), Hôpital Purpan [Toulouse], and 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)
Subjects: Male, medicine.medical_specialty, Adolescent, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Drug Resistance, Liver transplantation, Severity of Illness Index, Disability Evaluation, Young Adult, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Hepatolenticular Degeneration, Liver Function Tests, Modified Rankin Scale, Internal medicine, Severity of illness, Humans, Medicine, Survival rate, Retrospective Studies, medicine.diagnostic_test, business.industry, Parkinsonism, Retrospective cohort study, medicine.disease, Magnetic Resonance Imaging, Liver Transplantation, 3. Good health, Survival Rate, Female, 030211 gastroenterology & hepatology, Neurology (clinical), business, Liver function tests, 030217 neurology & neurosurgery
Abstract: ObjectiveTo evaluate the effect of liver transplantation (LT) in patients with Wilson disease (WD) with severe neurologic worsening resistant to active chelation.MethodsFrench patients with WD who underwent LT for pure neurologic indication were retrospectively studied. Before LT and at the last follow-up, neurologic impairment was evaluated with the Unified Wilson's Disease Rating Scale (UWDRS) score, disability with the modified Rankin Scale (mRS) score, and hepatic function with the Model for End-stage Liver Disease score, together with the presence of a Kayser-Fleischer ring (KFR), brain MRI scores, and copper balance. The survival rate and disability at the last follow-up were the coprimary outcomes; evolution of KFR and brain MRI were the secondary outcomes. Prognosis factors were further assessed.ResultsEighteen patients had LT. All were highly dependent before LT (median mRS score 5). Neurologic symptoms were severe (median UWDRS score 105), dominated by dystonia and parkinsonism. The cumulated survival rate was 88.8% at 1 year and 72.2% at 3 and 5 years. At the last follow-up, 14 patients were alive. Their mRS and UWDRS scores improved (p< 0.0001 andp= 0.0003). Eight patients had a major improvement (78% decrease of the UWDRS score), 4 a moderate one (41% decrease), and 2 a stable status. KFR and brain MRI scores improved (p= 0.0007). Severe sepsis (p= 0.011) and intensive care unit admission (p= 0.001) before LT were significantly associated with death.ConclusionsLT is a rescue therapeutic option that should be carefully discussed in selected patients with neurologic WD resistant to anticopper therapies (chelators or zinc salts) as it might allow patients to gain physical independency with a reasonable risk.Classification of evidenceThis study provides Class IV evidence that for patients with WD with severe neurologic worsening resistant to active pharmacologic therapy, LT might decrease neurologic impairment.
Published: 2020

43. A Randomized Controlled Trial of Bone–Patellar Tendon–Bone Anterior Cruciate Ligament Reconstruction With and Without Lateral Extra-articular Tenodesis: 19-Year Clinical and Radiological Follow-up

Author: Elvire Servien, Stanislas Gunst, Cécile Batailler, Sébastien Lustig, Philippe Neyret, Robert A. Magnussen, Marie Castoldi, Hôpital Pasteur [Nice] (CHU), Ohio State University [Columbus] (OSU), 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), Infirmerie Protestante, parent, Laboratoire de Biomécanique et Mécanique des Chocs (LBMC UMR T9406 ), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Gustave Eiffel
Subjects: Male, Anterior cruciate ligament reconstruction, medicine.medical_treatment, Osteoarthritis, ADOLESCENT, law.invention, Bone patellar tendon bone, 0302 clinical medicine, Randomized controlled trial, Risk Factors, law, RADIOGRAPHIE, Orthopedics and Sports Medicine, Extra-Articular, GENOU, HOMME, 030222 orthopedics, BONE-PATELLAR TENDON-BONE GRAFTING, RISK FACTOR, HUMAN, [SPI.MECA.BIOM]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], Osteoarthritis, Knee, musculoskeletal system, medicine.anatomical_structure, Radiological weapon, Bone-Patellar Tendon-Bone Grafting, Female, Adult, medicine.medical_specialty, Anterior cruciate ligament, Physical Therapy, Sports Therapy and Rehabilitation, 03 medical and health sciences, medicine, Humans, ADULTE, PATIENT REPORTED OUTCOME MEASURES, FOLLOW-UP STUDIES, business.industry, ANTERIOR CRUCIATE LIGAMENT INJURIES, YOUNG ADULT, LATERAL EXTRA-ARTICULAR TENODESIS, 030229 sport sciences, medicine.disease, TENODESIS, JOINT INSTABILITY, Surgery, Radiography, OSTEOARTHRITIS, ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION, FEMME, GRAFT SURVIVAL, BONE-PATELLAR TENDON-BONE, business, ANTERIOR CRUCIATE LIGAMENT
Abstract: Background: Arthroscopic anterior cruciate ligament (ACL) reconstruction (ACLR) with a bone–patellar tendon–bone graft (BTB) is a reliable surgical option for the control of anterior knee laxity after ACL injury. The addition of a lateral extra-articular tenodesis (LET) may improve control of rotation knee laxity and improve short-term graft survival in high-risk patients. Purpose: The aims of this study were to compare long-term patient-reported outcomes, graft survival, and risk of osteoarthritis between ACLR with and without LET. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: This study included 121 consecutive knees (120 patients) presenting to a single center with an ACL rupture between 1998 and 1999. In total, 61 knees were randomized to an isolated BTB ACLR, and 60 knees were randomized to a BTB ACLR with an extra-articular lateral tenodesis with gracilis tendon (modified Lemaire). Results: Eighty knees in 79 patients (66%) were available for follow-up at a postoperative mean of 19.4 years (range, 19-20.2). Of those patients, 43 had a clinical examination and completed patient-reported outcome questionnaires, and the other 37 patients were evaluated through the questionnaires alone. Standard radiographs were available for 45 patients and laximetry (TELOS) for 42 patients. Mean subjective International Knee Documentation Committee score at last follow-up was 81.8, and no differences were noted between the BTB and BTB-LET groups ( P = .7). Two-thirds of patients were still participating in pivoting sports. A total of 17 knees (21%) experienced a graft failure, 5 of which (6%) underwent revision ACLR. There was no significant difference in graft failure risk between the BTB group (29%) and the BTB-LET group (13%; P = .1). Lateral tibiofemoral osteoarthritis was significantly more frequent in the BTB-LET group (59%) as compared with the BTB group (22%; P = .02). Lateral compartment osteoarthritis was correlated with partial lateral meniscectomy. Conclusion: There were no significant differences in long-term patient-reported outcomes after ACLR with or without an LET. LET may increase the risk of lateral compartment osteoarthritis at long-term follow-up. There was a trend toward decreased graft failure risk with the addition of LET but this study was underpowered to assess this outcome.
Published: 2020

44. Nevirapine Use Is Associated with Higher Bone Mineral Density in HIV-1 Positive Subjects on Long-Term Antiretroviral Therapy

Author: Couffignal, Camille, Kolta, Sami, Flamant, Martin, Cazanave, Charles, Haymann, Jean-Philippe, Mentre, France, Duval, Xavier, Leport, Catherine, Raffi, Francois, Chêne, G., Salamon, R., Moatti, J., Pierret, J., Spire, B., Brun-Vézinet, F., Fleury, H., Masquelier, B., Peytavin, G., Garraffo, R., Costagliola, D., Dellamonica, P., Katlama, C., Meyer, L., Salmon, D., Cuzin, L., Dupon, M., Le Moing, V., Marchou, B., May, T., Morlat, P., Rabaud, C., Waldner-Combernoux, A., Hardel, L., Reboud, P., Couffin-Cadiergues, S., Marchand, L., Assuied, A., Carrieri, P., Habak, S., Couturier, F., Jadand, C., Perrier, A., Préau, M., Protopopescu, C., Schmit, J.L., Chennebault, J.M., Faller, J.P., Magy-Bertrand, N., Chirouze, C., Humbert, P., Neau, D., Granier, P., Ansart, S., Verdon, R., Merrien, D., Chevojon, P., Sobel, A., Levy, Y., Piroth, L., Perronne, C., Froguel, E., Ceccaldi, J., Chidiac, C., Grégoire, V., Reynes, J., Fuzibet, J., Arsac, P., Bouvet, E., Bricaire, F., Monsonego, J., Girard, P.M., Guillevin, L., Herson, S., Molina, J.M., Pialoux, G., Sain, O., Sellier, P., Roblot, F., Bani-Sadr, F., Michelet, C., Lucht, F., Debord, C., Martin, T., de Jaureguiberry, J.P., Bernard, L., Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Physiologie [Bichat-Claude Bernard], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Service des Maladies Infectieuses et Tropicales A [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Remodelage et Reparation du Tissu Renal, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Hôpital Bichat, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-UFR de Médecine, Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques (U738 / UMR_S738), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes (CHU Nantes), Epidémiologie, santé publique et développement, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Santé Publique, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Microbiologie Fondamentale et Pathogénicité (MFP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Pharmacie de l'Hôpital Bichat, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service des maladies infectieuses, Centre Hospitalier Universitaire de Nice (CHU Nice)-University Hospital, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Bell Labs (BELL), Lucent Technologies, Service des Maladies Infectieuses et Tropicales [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Amiens-Picardie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), service de maladies infectieuses CHU J Minjoz Besancon, Service de virologie et d'immunologie biologique, Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Unité de Maladies Infectieuses et Tropicales [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Département d'infectiologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service des Maladies Infectieuses et Tropicales [CHU Raymond Poincaré], Hôpital Raymond Poincaré [AP-HP], Centre Hospitalier Libourne, 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), Department of Radiation Oncology, Université Catholique de Louvain = Catholic University of Louvain (UCL), GERES - Groupe d'Étude sur le Risque d'Exposition des Soignants aux agents infectieux - Research Group for the Prevention of Occupational Infections in Healthcare Workers [Paris, France], Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Reims (CHU Reims), University Hospital and University Jean Monnet, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Institut National de la Santé et de la Recherche Médicale (INSERM)-UFR de Médecine-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des maladies infectieuses et tropicales [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), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Groupe d'Étude sur le Risque d'Exposition des Soignants aux agents infectieux (GERES), Cholley, Pascal, and Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière]
Subjects: Adult, Male, medicine.medical_specialty, Time Factors, Nevirapine, nevirapine, Immunology, Cumulative Exposure, HIV Infections, 03 medical and health sciences, Absorptiometry, Photon, 0302 clinical medicine, Bone Density, Virology, Internal medicine, medicine, Humans, Prospective Studies, 030212 general & internal medicine, 030304 developmental biology, Bone mineral, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Incidence (epidemiology), HIV, virus diseases, Odds ratio, Middle Aged, medicine.disease, Confidence interval, 3. Good health, Cross-Sectional Studies, Infectious Diseases, Cohort, HIV-1, Coinfection, Reverse Transcriptase Inhibitors, Female, bone mineral density, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Follow-Up Studies, medicine.drug
Abstract: International audience; We assessed bone mineral density (BMD) in a cohort of human immunodeficiency virus (HIV)-positive patients after a median of 11 years of combination antiretroviral therapy (cART) and evaluated the respective role of HIV infection and antiretroviral drugs (ARVs). A cross-sectional study of 162 participants (131 male) from the ANRS-C08 cohort was performed with bone dual-energy X-ray absorptiometry (DXA) scans and renal assessment. The window of exposure to ARVs was defined as an exposure of more than six cumulative months during the last 3 years before the DXA evaluation to account for a cumulative exposure that could affect bone remodeling. The association with low BMD (Z-score < -2) was assessed by a multiple logistic regression model. The study population was 50 years (median), hepatitis C virus (HCV) (18%), and hepatitis B virus (HBV) (8%) coinfection with HIV-RNA
Published: 2020

45. Specific PCR and Quantitative Real-Time PCR in Ocular Samples from Acute and Delayed-Onset Postoperative Endophthalmitis

Author: Pierre-Loïc Cornut, Max Maurin, Sandrine Boisset, François Vandenesch, Ralitsa Hubanova, Anne Carricajo, Florent Aptel, Gilles Thuret, Julie Kosacki, Christophe Chiquet, Université Grenoble Alpes (UGA), CHU Grenoble, Service d'Ophtalmologie [Hôpital Edouard Herriot - HCL]], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, and Clinique du Val d'Ouest
Subjects: Male, Microbiological culture, [SDV]Life Sciences [q-bio], Antibiotics, Visual Acuity, medicine.disease_cause, Polymerase Chain Reaction, Eye Infections, Bacterial, law.invention, Postoperative Complications, 0302 clinical medicine, Endophthalmitis, Staphylococcus epidermidis, law, Vitrectomy, Prospective Studies, Polymerase chain reaction, 0303 health sciences, biology, Staphylococcal Infections, Anti-Bacterial Agents, 3. Good health, Streptococcus pneumoniae, Staphylococcus aureus, Acute Disease, Female, Nucleic Acid Amplification Techniques, DNA, Bacterial, medicine.drug_class, Trabeculectomy, Cataract Extraction, Real-Time Polymerase Chain Reaction, DNA, Ribosomal, Microbiology, Aqueous Humor, 03 medical and health sciences, medicine, Humans, Aged, 030304 developmental biology, Bacteriological Techniques, business.industry, Eye infection, biology.organism_classification, medicine.disease, Vitreous Body, Ophthalmology, 030221 ophthalmology & optometry, business
Abstract: Rapid identification of virulent pathogens is essential to strengthen the therapeutic strategy of acute endophthalmitis.This study sought to compare the contribution of a combination of polymerase chain reaction (PCR)-based tests to culture methods, in patients with postoperative endophthalmitis.Prospective multicenter study diagnostic evaluation.Setting: university referral centers.153 consecutive patients presenting with acute or delayed-onset postoperative endophthalmitis, between 2008 and 2015. There were a total of 284 aqueous humor (AH) and/or vitreous fluid (VF) samples. Outcomes and measurements: microbiological tests of intraocular samples included bacterial culturing of pediatric blood culture bottles; 16SrDNA amplification and sequencing (panbacterial PCR) for detection and identification of all bacterial species; real-time PCR (qPCR) assays targeting the femA or lytA gene for detection of Staphylococcus aureus (S. aureus) or Streptococcus pneumoniae (S. pneumoniae), respectively; and a qPCR assay targeting the tuf gene for detection and quantification of Staphylococcus epidermidis (S. epidermidis).At the time of admission, the rate of detection of microorganisms by PCR-based tests was not significantly different than that by culturing (38% versus 30% in AH samples [n = 69]; 66% versus 63% in VF samples [n = 82], respectively). In contrast, after 1 intravitreal injection (IVI) of antibiotics, the identification rate by PCR-based tests was higher than that in VF by culturing (62% vs 48%, respectively; n = 94; P = 0.05). Bacteria were identified in 70% of patients, with a predominance of Gram-positive bacteria (93%). Specific qPCR tests targeting S. aureus and S. pneumoniae did not provide additional diagnoses but provided earlier results. The S. epidermidis load in vitreous at the time of patients' admission was higher in cases of final visual acuity (VA) of20/40 (127,118 ± 125,848 DNA copies/mL) in patients with a VA of ≥20/40 (40350,000 ± 46,912 DNA copies/mL; P = 0.09). No significant changes in S. epidermidis load was found after one IVI.Patients with acute or delayed-onset endophthalmitis should benefit from microbiological identification in vitreous samples by combined analysis using bacterial cultures in pediatric blood culture bottles and panbacterial PCR. The last test was more effective than cultures in vitreous samples collected after an IVI of antibiotics. The qPCR tests targeting S. aureus and S. pneumoniae gave earlier results than culture and panbacterial PCR but did not provide additional diagnoses. As for S. epidermidis infections, determination of bacterial load using the qPCR test targeting the tuf gene could help evaluation of the visual prognosis of patients. Its role in the follow-up of patients after antibiotic treatment needs further investigation.
Published: 2020

46. Effect of bile acid supplementation on endogenous lipid synthesis in patients with short bowel syndrome: A pilot study

Author: Laurent Brondel, Jocelyne Drai, M. Lauverjat, Michel Beylot, Cécile Chambrier, Thomas Mouillot, P. Gelas, Patrick Hillon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Lipides - Nutrition - Cancer (U866) (LNC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, and Hospices Civils de Lyon (HCL)
Subjects: Male, 0301 basic medicine, Pilot Projects, Critical Care and Intensive Care Medicine, Gastroenterology, chemistry.chemical_compound, Liver disease, 0302 clinical medicine, Nutrition and Dietetics, Bile acid, Middle Aged, Short bowel syndrome, Ursodeoxycholic acid, ursodeoxycholic acid, 3. Good health, Cholesterol, gas-chromatography, Female, acid, medicine.drug, Adult, spectroscopy, medicine.medical_specialty, cholesterol-synthesis, medicine.drug_class, water, parenteral nutrition, 030209 endocrinology & metabolism, short bowel syndrome, Bile Acids and Salts, intestinal-failure, Young Adult, 03 medical and health sciences, total parenteral-nutrition, lipid, Internal medicine, medicine, Humans, Triglycerides, Aged, 030109 nutrition & dietetics, business.industry, Lipogenesis, hepatic lipogenesis, cholestatic liver-disease, Lipid metabolism, medicine.disease, Parenteral nutrition, intestinal failure-associated liver disease, chemistry, Dietary Supplements, Steatosis, business, metabolism, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, ursodeoxycholic
Abstract: International audience; Background & aims: Short bowel syndrome patients (SBS) receiving parenteral nutrition (PN) often have dyslipidaemia and can develop intestinal failure-associated liver disease (IFALD). These patients demonstrate increased cholesterol synthesis and hepatic lipogenesis. These lipid disturbances may be due to a decreased concentration of the bile acid pool or malabsorption. The aim of this pilot study was to evaluate the effect of bile acid administration on lipid synthesis in patients with SBS. Methods: The 24 h fractional synthesis rate (FSR) of cholesterol and triglycerides was measured by the isotopic method (deuterated water) before and after 4 months of ursodeoxycholic acid (UDCA) treatment (20 mg/kg/day). Five short bowel patients (age: 53.4 +/- 19.2 years) who had normal liver function and lipid plasmatic profiles received 1920 +/- 300 ml of PN for 151 +/- 74 days (mean PN energy intake was 27.0 +/- 6.0 kcal/kg body weight, composed with 3.87 +/- 1.38 g/kg of carbohydrate, 0.72 +/- 0.25 g/kg of fat and 1.10 +/- 0.23 g/kg of amino acids). Plasma metabolites, liver enzymes, 7-cc-OH-cholesterol and steatosis levels were also evaluated before and after treatment. Student's t-tests were performed, and the results were expressed in means (+/- SD). Results: After treatment, decreases in the absolute values of cholesterol synthesis (0.31 +/- 0.12 mmol L-1 to 0.24 +/- 0.11 mmol L-1; p < 0.05), FSR of cholesterol (31.6 +/- 4.7% to 26.4 +/- 4.7%; p = 0.06) and FSR of triglycerides (12.8 +/- 5.8% to 9.2 +/- 5.5%; p < 0.01) were observed. Cholesterol and alanine aminotrans-ferase concentrations also decreased (ALT) (p < 0.05). The absolute values of triglyceride synthesis and triglyceride concentrations remained unchanged. Conclusions: In SBS patients, UDCA decreases the hepatic synthesis of triglycerides and cholesterol. These results suggest that UDCA could prevent the onset of the IFALD. (C) 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism.
Published: 2020

47. Widening of the genetic and clinical spectrum of Lamb-Shaffer syndrome, a neurodevelopmental disorder due to SOX5 haploinsufficiency

Author: Ashley N. Sigafoos, Salima El Chehadeh, Marcia C. Willing, Ela Akay, Florian Cherik, Anne-Marie E. Goyette, Vinodh Narayanan, Diane Masser-Frye, Catherine Karimov, Rhonda E. Schnur, Rebekah Bressi, Rhys H. Thomas, Gary D. Clark, Tina Barbaro-Dieber, Jill A. Rosenfeld, Carlos A. Bacino, Maria J. Guillen Sacoto, Laura Russell, Kristin Lindstrom, Caroline Schluth-Bolard, Xia Wang, Yvonne Hilhorst-Hofstee, Marcelo Vargas, Zehua Zhu, Ash Zawerton, Boris Keren, Mariëtte J.V. Hoffer, Isabelle Marey, Alice Poisson, Daphné Lehalle, Maries Joseph, Gaetan Lesca, Simon Zwolinski, Laurence Perrin, Rhoda Akilapa, Emilia K. Bijlsma, Christel Depienne, Amélie Piton, Claire G. Salter, Lucie Dupuis, Daryl A. Scott, Jolien S. Klein Wassink-Ruiter, Benjamin Cogné, Mathilde Nizon, Richard Chang, Kirsty McWalter, Myriam Srour, Perrine Charles, Anne-Claude Tabet, Natalie Canham, Sylvie Odent, Caroline Nava, Karl J. Clark, Elizabeth J. Bhoj, Jonathan Levy, Keri Ramsey, Yves Alembik, Lucia Ortega, Sophie Dupuis-Girod, Shoji Ichikawa, Christine Francannet, Marta Bertoli, Christèle Dubourg, Eric W. Klee, Ange-Line Bruel, Sebastien Moutton, Emily Fassi, Anthony Vandersteen, Abdul Haseeb, Antonina Wojcik, Patrick R. Blackburn, Lynne M. Bird, Patrick Rump, Véronique Lefebvre, Alma Kuechler, Sophie Nambot, Keren Machol, Cyril Mignot, Andreas Hartmann, Rossana Sanchez Russo, Erica H. Gerkes, Sylvie Jaillard, Roberto Mendoza-Londono, Trevor Cole, Pauline Monin, Cleveland Clinic, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Département de génétique [Robert Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Hospices Civils de Lyon (HCL), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Center for Human and Clinical Genetics, Leiden University Medical Center (LUMC), Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Health Sciences Research [Mayo Clinic] (HSR), Mayo Clinic, This research was funded in part by the Agence Nationale de la Recherche and European High-Functioning Autism Network (ANR EUHFAUTISM), the Assistance Publique–Hôpitaux de Paris (AP-HP), the Institut National de la Santé et de la Recherche Médicale (INSERM), the BioPsy labex (to Christel Depienne and C.N.) and the Association Française du Syndrome Gilles de la Tourette (AFSGT) to Christel Depienne. It was also funded by the Cleveland Clinic Lerner Research Institute (LRI Chair’s Innovative Research Award to V.L.), and by Harper’s Quest and the LAMSHF Syndrome Research Fund (donations to V.L.) and the Center for Individualized Medicine, Mayo Clinic. This study makes use of data generated by the DECIPHER community and the Deciphering Developmental Disorders (DDD) Study, which is funded by the Wellcome Trust. The DDD study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between Wellcome and the Department of Health, and the Wellcome Sanger Institute (grant number WT098051). The views expressed in this publication are those of the author(s) and not necessarily those of Wellcome or the Department of Health. The study has UK Research Ethics Committee approval (10/H0305/83, granted by the Cambridge South REC, and GEN/284/12 granted by the Republic of Ireland REC). The research team acknowledges the support of the National Institute for Health Research, through the Comprehensive Clinical Research Network., We thank the patients and their families for their participation in this study, and the C4RCD Research Group (Newell Belnap, Amanda Courtright, Ana Claasen, David Craig, Matt Huentelman, Madison LaFleur, Sampathkumar Rangasamy, Ryan Richholt, Isabelle Schrauwen, Ashley L. Siniard, and Szabolics Szelinger) for providing clinical information on patient P18., Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Génétique et Cytogénétique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP Hôpital universitaire Robert-Debré [Paris], Centre d'Exploration et de Recherche Médicales par Émission de Positons (CERMEP), Université Joseph Fourier - Grenoble 1 (UJF)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, Medizin, Haploinsufficiency, L-SOX5, VARIANTS, 0302 clinical medicine, Neurodevelopmental disorder, Intellectual disability, Missense mutation, 2.1 Biological and endogenous factors, Aetiology, Child, Genetics (clinical), Genetics, Pediatric, Genetics & Heredity, 0303 health sciences, Pedigree, FAMILY, DNA-Binding Proteins, developmental delay, TRANSCRIPTION FACTORS, Phenotype, intellectual disability, Child, Preschool, missense variants, Female, SOXD Transcription Factors, Adult, EXPRESSION, Adolescent, Intellectual and Developmental Disabilities (IDD), Clinical Sciences, Mutation, Missense, autism, Cell fate determination, Biology, LONG FORM, SEQUENCE, Article, 03 medical and health sciences, Young Adult, Rare Diseases, Clinical Research, CARTILAGE, Intellectual Disability, medicine, Animals, Humans, Language Development Disorders, Genetic Predisposition to Disease, Preschool, Transcription factor, Gene, 030304 developmental biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, MUTATIONS, Human Genome, Infant, medicine.disease, Brain Disorders, Neurodevelopmental Disorders, Deciphering Developmental Disorder Study, Mutation, Autism, epilepsy, Missense, 030217 neurology & neurosurgery, GENERATION
Abstract: International audience; PURPOSE: Lamb-Shaffer syndrome (LAMSHF) is a neurodevelopmental disorder described in just over two dozen patients with heterozygous genetic alterations involving SOX5, a gene encoding a transcription factor regulating cell fate and differentiation in neurogenesis and other discrete developmental processes. The genetic alterations described so far are mainly microdeletions. The present study was aimed at increasing our understanding of LAMSHF, its clinical and genetic spectrum, and the pathophysiological mechanisms involved.METHODS: Clinical and genetic data were collected through GeneMatcher and clinical or genetic networks for 41 novel patients harboring various types of SOX5 alterations. Functional consequences of selected substitutions were investigated.RESULTS: Microdeletions and truncating variants occurred throughout SOX5. In contrast, most missense variants clustered in the pivotal SOX-specific high-mobility-group domain. The latter variants prevented SOX5 from binding DNA and promoting transactivation in vitro, whereas missense variants located outside the high-mobility-group domain did not. Clinical manifestations and severity varied among patients. No clear genotype-phenotype correlations were found, except that missense variants outside the high-mobility-group domain were generally better tolerated.CONCLUSIONS:This study extends the clinical and genetic spectrum associated with LAMSHF and consolidates evidence that SOX5 haploinsufficiency leads to variable degrees of intellectual disability, language delay, and other clinical features.
Published: 2020

48. Cisplatin unleashes Toll-like receptor 3-mediated apoptosis through the downregulation of c-FLIP in malignant mesothelioma

Author: Serge Lebecque, Sylvie Lantuejoul, Kathrin Weber, Yann Estornes, Marc Grégoire, Toufic Renno, Olivier Micheau, Thomas Daunizeau, Audrey Ziverec, Marion Delphin, Béatrice Vanbervliet-Defrance, Tiphaine Delaunay, Leila Djemal, Christophe Blanquart, Karene Mahtouk, Jean-François Fonteneau, Vahan Kepenekian, Guillaume Passot, Olivier Glehen, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunogenic Cell Death and Mesothelioma Therapy (CRCINA-ÉQUIPE 4), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), LabEX IGO Immunothérapie Grand Ouest, Service de Chirurgie Viscérale et Oncologique (Centre Hospitalier Lyon Sud [CHU - HCL] CHLS), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Ciblage thérapeutique en Oncologie (EA3738), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Department of Biopathology and Translation Research and Innovation [Centre Léon Bérard, Lyon], Centre Léon Bérard [Lyon], Synergie Lyon Cancer [Lyon], Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Service D'Anatomie Pathologique (Centre Hospitalier Lyon Sud [CHU - HCL] CHLS ), Bernardo, Elizabeth, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Nantes Université (Nantes Univ), and Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement
Subjects: Mesothelioma, 0301 basic medicine, Cancer Research, Programmed cell death, Lung Neoplasms, viruses, Cell, CASP8 and FADD-Like Apoptosis Regulating Protein, Apoptosis, [SDV.CAN]Life Sciences [q-bio]/Cancer, chemical and pharmacologic phenomena, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Downregulation and upregulation, Cell Line, Tumor, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Cell Proliferation, Inflammation, Cisplatin, Caspase 8, Chemistry, Mesothelioma, Malignant, hemic and immune systems, medicine.disease, Toll-Like Receptor 3, 3. Good health, Gene Expression Regulation, Neoplastic, Poly I-C, 030104 developmental biology, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Immune receptor, TLR3, Cancer research, Peritoneal mesothelioma, Therapy, Signal Transduction, medicine.drug
Abstract: International audience; Toll-like receptor 3 (TLR3) is an immune receptor that behaves like a death receptor in tumor cells, thereby providing an original target for cancer therapy. The therapeutic potential of TLR3 targeting in malignant mesothelioma, an aggressive and incurable neoplasia of the pleura and peritoneum, has so far not been addressed. We investigated TLR3 expression and sensitivity of human mesothelioma cell lines to the synthetic dsRNA Poly (I:C), alone or in combination with cisplatin, the gold standard chemotherapy in mesothelioma. Activation of TLR3 by Poly(I:C) induced apoptosis of 4/8 TLR3-positive cell lines but not of TLR3-negative cell lines. The combined cisplatin/Poly(I:C) treatment enhanced apoptosis of 3/4 Poly(I:C)-sensitive cell lines and overcame resistance to Poly(I:C) or cisplatin alone in 2/4 cell lines. Efficacy of the combined treatment relied on cisplatininduced downregulation of c-FLIP, the main regulator of the extrinsic apoptotic pathway, leading to an enhanced caspase-8-mediated pathway. Of note, 6/6 primary cell samples isolated from patients with peritoneal mesothelioma expressed TLR3. Patient-derived cells were sensitive to Poly(I:C) alone while the combined cisplatin/Poly(I:C) treatment induced dramatic cell death. Our findings demonstrate that TLR3 targeting in combination with cisplatin presents an innovative therapeutic strategy in mesothelioma.
Published: 2020

49. Right Colectomy with Absorbable Mesh Repair as a Salvage Solution for the Management of Giant Incisional Hernia with Loss of Domain: Results of a Bicentric Study

Author: David Moszkowicz, Maud Robert, Jean-Luc Bouillot, Marie-Cécile Blanchet, Olivier Benoit, Dominique Cabral, Laurent Milot, Frédérique Peschaud, CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU), Centre de Recherche et d'Application en Traitement de l'Image et du Signal (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)-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), 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), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Adult, Male, medicine.medical_specialty, Abdominal compartment syndrome, Incisional hernia, [SDV]Life Sciences [q-bio], medicine.medical_treatment, 030230 surgery, 03 medical and health sciences, 0302 clinical medicine, Pneumoperitoneum, Laparotomy, medicine, Humans, Incisional Hernia, Hernia, Colectomy, Herniorrhaphy, Aged, Retrospective Studies, Aged, 80 and over, business.industry, Middle Aged, Surgical Mesh, medicine.disease, Hernia repair, 3. Good health, Surgery, 030220 oncology & carcinogenesis, Right Colectomy, Female, business, Abdominal surgery
Abstract: BACKGROUND: Incisional hernia (IH) may occur in 20% of patients after laparotomy. The hernia sac volume may be of significance, with reintegration of visceral contents potentially leading to repair failure or abdominal compartment syndrome. The present study aimed to evaluate a two-step surgical strategy comprising right colectomy for hernia reduction with synchronous absorbable mesh repair followed by definitive non-absorbable mesh repair in recurrence. METHODS: Patients operated between 2012 and 2017 at two university centers were retrospectively included. Volumetric evaluation of the IH was performed by CT imaging. RESULTS: Eleven patients were included. The mean BMI was 43 kg/m(2) (23-52 kg/m(2)). Progressive preoperative pneumoperitoneum was performed in 82% of patients, with complications in 22%. The mean volumetric ratio of the volume of the hernia to the volume of the abdominal cavity was 70% (48-100%). The first parietal repair was performed using an synthetic absorbable mesh (36%), a biologic mesh (27%), or a slowly absorbable mesh (36%). No patients died as a result of the procedure. Seven (64%) patients developed grade III-IV complications, including one case of an anastomotic fistula. Recurrence occurred in eight (73%) patients after the first repair. Of these, four (50%) patients were reoperated using a non-absorbable mesh, leading to solid repair in 75% of cases. After 27 ± 18 months of follow-up, the residual IH rate was 46%. CONCLUSIONS: Right colectomy for volume reduction in IH with loss of domain potentially represents an appropriate salvage option, supporting bowel reintegration and temporary hernia repair with absorbable material.
Published: 2020

50. Uraemic toxin‐induced inflammation and oxidative stress in human endothelial cells: protective effect of polyphenol‐rich extract from açaí

Author: Patricia Leticia Trindade, Angela Castro Resende, Graziele Freitas de Bem, Christophe O. Soulage, Julio Beltrame Daleprane, Elaine Soares, Magna Cottini Fonseca Passos, Elisa B. Monteiro, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National de la Recherche Agronomique (INRA)
Subjects: Acai, Necrosis, Euterpe, Physiology, [SDV]Life Sciences [q-bio], uremic toxins, Inflammation, 030204 cardiovascular system & hematology, Pharmacology, Protective Agents, medicine.disease_cause, Antioxidants, endothelial dysfunction, Superoxide dismutase, 03 medical and health sciences, 0302 clinical medicine, Physiology (medical), Human Umbilical Vein Endothelial Cells, medicine, Humans, oxidative stress, Secretion, Viability assay, Renal Insufficiency, Chronic, Endothelial dysfunction, Cells, Cultured, Nutrition and Dietetics, Cell Death, biology, Plant Extracts, Superoxide Dismutase, Chemistry, Polyphenols, General Medicine, medicine.disease, Endothelial stem cell, inflammation, biology.protein, Cytokines, medicine.symptom, Biomarkers, chronic kidney disease, 030217 neurology & neurosurgery, Oxidative stress
Abstract: NEW FINDING: What is the central question of this study? Polyphenols shows protective cardiometabolic actions in different disease models. A potential role of a polyphenols-rich extract from acai in preventing uremic toxin-induced endothelial dysfunction in endothelial cells has not been previously reported. What is the main finding and its importance? We showed that polyphenols from acai prevented cell death, restored the migratory capacity, protected from inflammation and contributed to antioxidant response restoration in endothelial cells exposed to uremic toxins. The protective role of acai from toxic effects exerted by uremic toxins presents a potential new therapeutic target in endothelial cells. ABSTRACT: Aims In chronic kidney disease (CKD), progressive loss of kidney function results in the accumulation of protein-bound uremic toxins such as p-cresyl-sulfate (p-CS) and indoxyl sulfate (IS). Among strategies to ameliorate uremic toxin harmful actions, phenolic compounds have been extensively studied. The main goal of this work was to evaluate the antioxidant and anti-inflammatory actions of phenolic-rich acai seed extract (ASE), in response to endothelial dysfunction induced by IS and p-CS, in human umbilical vein endothelial cells (HUVEC). Main methods Cells were treated with ASE (10 mug/mL) in the presence or absence of IS (61 mug/mL) and p-CS (40 mug/mL). Cell viability, cell death, cell migratory capacity and inflammatory biomarker expression were evaluated. Cellular antioxidant response was measured through the activity and expression of antioxidant enzymes and oxidative damage was evaluated. Key findings IS and p-CS lowered cell viability, triggered cell death and lowered the migratory capacity in endothelial cells (p \textless 0.05). ASE prevented cell death and restored the migratory capacity in cells exposed to IS. Both toxins up-regulated pro-inflammatory cytokine expression and ASE was able to beneficially counteract this effect. TNF-alpha secretion was greater in uremic toxins treated cells and ASE reversed this phenomenon in cells treated with both toxins concomitantly (p \textless 0.05). Regarding the antioxidant response, superoxide dismutase expression was strikingly lower in cells treated with both toxins, and ASE inhibited this harmful effect (p \textless 0.05). Significance From the results above, we conclude that ASE exerted protective effects on inflammation and oxidative stress caused by uremic toxins (particularly by IS) in human endothelial cells. This article is protected by copyright. All rights reserved.
Published: 2020

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

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

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Journal

Database

Publisher

4,100 results on '"Hospices Civils de Lyon (HCL)"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources