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5,931 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. The role of Monte Carlo simulation in understanding the performance of proton computed tomography

Author

Simon Rit, Jannis Dickmann, Sebastian Meyer, George Dedes, Reinhard W. Schulte, Nils Krah, R. P. Johnson, Vladimir Bashkirov, V. Giacometti, Katia Parodi, Guillaume Landry, Department of Medical Physics, Ludwig-Maximilians-Universität München (LMU), 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), PRISME (PRISME), Institut de Physique des 2 Infinis de Lyon (IP2I Lyon), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Loma Linda University, University of California [Santa Cruz] (UCSC), and University of California

Subjects
Proton computed tomography, Scanner, Computer science, Physics::Medical Physics, Monte Carlo method, ComputingMethodologies_IMAGEPROCESSINGANDCOMPUTERVISION, Biophysics, Iterative reconstruction, 030218 nuclear medicine & medical imaging, Computational science, 03 medical and health sciences, 0302 clinical medicine, proton therapy, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Radiology, Nuclear Medicine and imaging, Tomography, Image resolution, Proton therapy, Monte Carlo simulation, proton computed tomography, Tomographic reconstruction, Radiological and Ultrasound Technology, Phantoms, Imaging, Detector, relative proton stopping power, Protons, Monte Carlo Method
Abstract

International audience; Proton computed tomography (pCT) is a promising tomographic imaging modality allowing direct reconstruction of proton relative stopping power (RSP) required for proton therapy dose calculation. In this review article, we aim at highlighting the role of Monte Carlo (MC) simulation in pCT studies. After describing the requirements for performing proton computed tomography and the various pCT scanners actively used in recent research projects, we present an overview of available MC simulation platforms. The use of MC simulations in the scope of investigations of image reconstruction, and for the evaluation of optimal RSP accuracy, precision and spatial resolution omitting detector effects is then described. In the final sections of the review article, we present specific applications of realistic Monte Carlo simulations of an existing pCT scanner prototype, which we describe in detail.

Published
2022

3. 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

4. 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

5. Improving motion‐mask segmentation in thoracic CT with multiplanar U‐nets

Author

Nicolas Pinon, Maciej Orkisz, Jean-Christophe Richard, Ludmilla Penarrubia, Eduardo Enrique Dávila Serrano, David Sarrut, Emmanuel Roux, 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), 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), Service de Réanimation Médicale, Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), and Imagerie Tomographique et Radiothérapie

Subjects
Lung Neoplasms, Computer science, Image registration, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Robustness (computer science), Carcinoma, Non-Small-Cell Lung, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Image Processing, Computer-Assisted, Humans, Segmentation, Generalizability theory, Computer vision, Four-Dimensional Computed Tomography, Artificial neural network, SARS-CoV-2, business.industry, Deep learning, Process (computing), COVID-19, General Medicine, 3. Good health, 030220 oncology & carcinogenesis, Memory footprint, Artificial intelligence, business
Abstract

International audience; Purpose. Motion-mask segmentation from thoracic computed tomography (CT) images is the process of extracting the region that encompasses lungs and viscera, where large displacements occur during breathing. It has been shown to help image registration between different respiratory phases. This registration step is, for example, useful for radiotherapy planning or calculating local lung ventilation. Knowing the location of motion discontinuity, that is, sliding motion near the pleura, allows a better control of the registration preventing unrealistic estimates. Nevertheless, existing methods for motion-mask segmentation are not robust enough to be used in clinical routine. This article shows that it is feasible to overcome this lack of robustness by using a lightweight deep-learning approach usable on a standard computer, and this even without data augmentation or advanced model design.Methods. A convolutional neural-network architecture with three 2D U-nets for the three main orientations (sagittal, coronal, axial) was proposed. Predictions generated by the three U-nets were combined by majority voting to provide a single 3D segmentation of the motion mask. The networks were trained on a database of nonsmall cell lung cancer 4D CT images of 43 patients. Training and evaluation were done with a K-fold cross-validation strategy. Evaluation was based on a visual grading by two experts according to the appropriateness of the segmented motion mask for the registration task, and on a comparison with motion masks obtained by a baseline method using level sets. A second database (76 CT images of patients with early-stage COVID-19), unseen during training, was used to assess the generalizability of the trained neural network.Results. The proposed approach outperformed the baseline method in terms of quality and robustness: the success rate increased from urn:x-wiley:00942405:media:mp15347:mp15347-math-0001 to urn:x-wiley:00942405:media:mp15347:mp15347-math-0002 without producing any failure. It also achieved a speed-up factor of 60 with GPU, or 17 with CPU. The memory footprint was low: less than 5 GB GPU RAM for training and less than 1 GB GPU RAM for inference. When evaluated on a dataset with images differing by several characteristics (CT device, pathology, and field of view), the proposed method improved the success rate from urn:x-wiley:00942405:media:mp15347:mp15347-math-0003 to urn:x-wiley:00942405:media:mp15347:mp15347-math-0004.Conclusion. With 5-s processing time on a mid-range GPU and success rates around urn:x-wiley:00942405:media:mp15347:mp15347-math-0005, the proposed approach seems fast and robust enough to be routinely used in clinical practice. The success rate can be further improved by incorporating more diversity in training data via data augmentation and additional annotated images from different scanners and diseases. The code and trained model are publicly available.

Published
2021

6. 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

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. Molar Sodium Lactate Attenuates the Severity of Postcardiac Arrest Syndrome: A Preclinical Study

Author

Gabriel Bidaux, Laurent Argaud, Louis Kreitmann, Neven Stevic, Martin Cour, Michel Ovize, Laurent Desmurs, Joseph Loufouat, CarMeN, laboratoire, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), and 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)

Subjects
Male, Molar, Mean arterial pressure, Cardiac output, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Sodium, Hemodynamics, Diuresis, chemistry.chemical_element, cardiac arrest, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, Random Allocation, sodium lactate, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine, Sodium lactate, Animals, Post-Cardiac Arrest Syndrome, Saline, business.industry, brain mitochondria, Brain, 030208 emergency & critical care medicine, 3. Good health, [SDV] Life Sciences [q-bio], Disease Models, Animal, chemistry, postcardiac arrest syndrome, Anesthesia, Rabbits, business
Abstract

International audience; OBJECTIVES: To determine whether continuous IV infusion of molar sodium lactate would limit cardiac arrest-induced neurologic injury and cardiovascular failure. DESIGN: Randomized blinded study (animal model). SETTING: University animal research facility. SUBJECTS: Twenty-four adult male "New Zealand White" rabbits. INTERVENTIONS: Anesthetized rabbits underwent 12.5 minutes of asphyxial cardiac arrest and were randomized to receive either normal saline (control group, n = 12) or molar sodium lactate (molar sodium lactate group, n = 12) at a rate of 5 mL/kg/hr during the whole 120-minute reperfusion period. MEASUREMENTS AND MAIN RESULTS: Pupillary reactivity (primary outcome), levels of S100β protein, in vitro brain mitochondria functions, cardiovascular function, and fluid balance were assessed. Molar sodium lactate reduced brain injury, with a higher proportion of animals exhibiting pupillary reactivity to light (83% vs 25% in the CTRL group, p = 0.01) and lower S100β protein levels (189 ± 42 vs 412 ± 63 pg/mL, p \textless 0.01) at the end of the protocol. Molar sodium lactate significantly prevented cardiac arrest-induced decrease in oxidative phosphorylation and mitochondrial calcium-retention capacity compared with controls. At 120 minutes of reperfusion, survival did not significantly differ between the groups (10/12, 83% in the molar sodium lactate group vs nine of 12, 75% in the control group; p \textgreater 0.99), but hemodynamics were significantly improved in the molar sodium lactate group compared with the control group (higher mean arterial pressure [49 ± 2 vs 29 ± 3 mm Hg; p \textless 0.05], higher cardiac output [108 ± 4 vs 58 ± 9 mL/min; p \textless 0.05], higher left ventricle surface shortening fraction [38% ± 3% vs 19% ± 3%; p \textless 0.05], and lower left ventricular end-diastolic pressure [3 ± 1 vs 8 ± 2 mm Hg; p \textless 0.01]). While fluid intake was similar in both groups, fluid balance was higher in control animals (11 ± 1 mL/kg) than that in molar sodium lactate-treated rabbits (1 ± 3 mL/kg; p \textless 0.01) due to lower diuresis. CONCLUSIONS: Molar sodium lactate was effective in limiting the severity of the postcardiac arrest syndrome. This preclinical study opens up new perspectives for the treatment of cardiac arrest.

Published
2021

10. 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

11. In Vivo Evaluation of the Efficacy and Safety of a Novel Degradable Polymeric Film for the Prevention of Intrauterine Adhesions

Author

S. Huberlant, Salome Leprince, Vincent Letouzey, Renaud de Tayrac, Sophie Warembourg, Isabelle Leteuff, Lucie Allegre, Xavier Garric, Hubert Taillades, Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service de Gynécologie et Obstétrique [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)

Subjects
Male, medicine.medical_specialty, animal structures, Adhesions, medicine.medical_treatment, Rat model, Urology, Tissue Adhesions, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, medicine.disease_cause, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Pregnancy, In vivo, Hyaluronic acid, medicine, Animals, Humans, Animal model, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Hyaluronic Acid, Rats, Wistar, Good practice, Intrauterine, Medical device, Uterine Diseases, 030219 obstetrics & reproductive medicine, Biologic response, business.industry, [SDV.BA]Life Sciences [q-bio]/Animal biology, Obstetrics and Gynecology, Curettage, Rats, 3. Good health, medicine.anatomical_structure, chemistry, Case-Control Studies, 030220 oncology & carcinogenesis, embryonic structures, Female, Uterine cavity, Irritation, business, Synechiae
Abstract

Study Objective To study the safety of a degradable polymeric film (DPF) and its efficacy on reducing the risk of intrauterine-adhesion (IUA) formation in a rat model. Design A series of case-control studies relying on random allocation, where feasible. Setting University and good practice animal laboratories. Animals The animal models comprised female and male Oncins France Strain A and female Wistar rats. Intervention(s) and Measurements The Oncins France Strain A rats were used for in vivo evaluation of the impact of the DPF on endometrial thickness and its effect on fertility. For in vivo evaluation of the biologic response, 40 Wistar rats were randomly allocated to intervention and control groups, with matched sampling time after surgery. Finally, for the in vivo evaluation of the DPF's efficacy on IUA prevention, a total of 24 Wistar rats were divided into 3 groups: 1 treated with the DPF, 1 treated with hyaluronic acid gel, and a sham group. Main Results The DPF did not have a significant impact on endometrial thickness, and there were no significant differences in the number of conceived or prematurely terminated pregnancies, confirming its noninferiority to no treatment. The DPF did not induce irritation at 5 days and 28 days. Finally, the DPF significantly reduced the likelihood of complete IUA formation compared with hyaluronic acid gel– and sham-implanted animals, where only 27% of the animals had their uterine cavity obliterated compared with 80% and 100%, respectively. Conclusion The DPF is a safe film that is effective in preventing IUA formation after intrauterine curettage in rats.

Published
2021

12. 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

13. 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

14. 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

15. Real Time Intraoperative Functional Brain Mapping Based on RGB Imaging

Author

C. Caredda, Michaël Sdika, Jacques Guyotat, Raphaël Sablong, Bruno Montcel, Laurent Mahieu-Williame, RMN et optique : De la mesure au biomarqueur, 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), Plateforme d'Imagerie Multimodale LyonTech (PILoT), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), and Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL)

Subjects
[SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Computer science, [SDV]Life Sciences [q-bio], 0206 medical engineering, Biomedical Engineering, Biophysics, 02 engineering and technology, Human brain, 020601 biomedical engineering, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Functional brain, 0302 clinical medicine, Optical imaging, medicine.anatomical_structure, Robustness (computer science), Cortex (anatomy), medicine, White light, RGB color model, Neuroscience, ComputingMilieux_MISCELLANEOUS, Electrical brain stimulation
Abstract

Intraoperative optical imaging is a localization technique for the functional areas of the human brain cortex during neurosurgical procedures. However, it still lacks robustness to be used as a clinical standard. In particular new biomarkers of brain functionality with improved sensitivity and specificity are needed. We present a method for the real time identification of the activated cortical areas based on the analysis of the cortical hemodynamic using a RGB camera and a white light source. We measure the quantitative oxy and deoxy-hemoglobin concentration changes in the human brain cortex with the modified Beer-Lambert law and Monte Carlo simulations. A functional model has been implemented to define in real time a binary biomarker of the cortical activation following neuronal activation by physiological stimuli. The results show a good correlation between the computed activation maps and the brain areas localized by electrical brain stimulation. We demonstrate that a RGB camera combined with a quantitative modeling of brain hemodynamics biomarkers can evaluate in real time the functional areas during neurosurgery and serve as a tool of choice to complement electrical brain stimulation.

Published
2021

16. PET metabolic imaging of time-dependent reorganization of olfactory cued fear memory networks in rats

Author

Anne-Marie Mouly, Philippe Litaudon, Nadine Ravel, Nicolas Costes, Caroline Bouillot, Luc Zimmer, 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), 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), Hospices Civils de Lyon (HCL), RAVEL, Nadine, 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), MOULY, Anne-Marie, 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
[SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Cognitive Neuroscience, [SDV]Life Sciences [q-bio], Hippocampus, Sensory system, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Piriform cortex, Odor, Animals, Fear conditioning, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Prefrontal cortex, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Memory Consolidation, Cued speech, 0303 health sciences, Recall, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, Fear, Cued Fear conditioning, Recent memory, Odor fear conditioning, Rats, [SDV] Life Sciences [q-bio], [18F]FDG micro PET, Positron-Emission Tomography, Mental Recall, Memory consolidation, System-level consolidation, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Remote memory, Cues, Psychology, Neuroscience, 030217 neurology & neurosurgery
Abstract

Memory consolidation involves reorganization at both the synaptic and system levels. The latter involves gradual reorganization of the brain regions that support memory and has been mostly highlighted using hippocampal-dependent tasks. The standard memory consolidation model posits that the hippocampus becomes gradually less important over time in favor of neocortical regions. In contrast, this reorganization of circuits in amygdala-dependent tasks has been less investigated. Moreover, this question has been addressed using primarily lesion or cellular imaging approaches thus precluding the comparison of recent and remote memory networks in the same animals. To overcome this limitation, we used microPET imaging to characterize, in the same animals, the networks activated during the recall of a recent versus remote memory in an olfactory cued fear conditioning paradigm. The data highlighted the drastic difference between the extents of the two networks. Indeed, although the recall of a recent odor fear memory activates a large network of structures spanning from the prefrontal cortex to the cerebellum, significant activations during remote memory retrieval are limited to the piriform cortex. These results strongly support the view that amygdala-dependent memories also undergo system-level reorganization, and that sensory cortical areas might participate in the long-term storage of emotional memories.

Published
2022

17. Estimating Arterial Wall Deformations from Automatic Key-Point Detection and Matching

Author

Sami Qorchi, Maciej Orkisz, Didier Vray, Modeling & analysis for medical imaging and Diagnosis (MYRIAD), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Imagerie Ultrasonore

Subjects
Acoustics and Ultrasonics, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Computer science, 0206 medical engineering, Biophysics, Robust statistics, 02 engineering and technology, Motion estimation, Translation (geometry), 030218 nuclear medicine & medical imaging, Motion, 03 medical and health sciences, 0302 clinical medicine, Robustness (computer science), Ultrasound, Humans, Radiology, Nuclear Medicine and imaging, Computer vision, Arterial wall motion, Ultrasonography, [SPI.ACOU]Engineering Sciences [physics]/Acoustics [physics.class-ph], Ground truth, Radiological and Ultrasound Technology, business.industry, Compression (physics), 020601 biomedical engineering, Carotid Arteries, Outlier, Artificial intelligence, Affine transformation, business, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Carotid artery
Abstract

International audience; Assessing arterial-wall motion and deformations may reveal pathologic alterations in biomechanical properties of the parietal tissues and, thus, contribute to the detection of vascular disease onset. Ultrasound image sequences allow the observation of this motion and many methods have been developed to estimate temporal changes in artery diameter and wall thickness and to track 2-D displacements of selected points. Some methods enable the assessment of shearing or stretching within the wall, but none of them can estimate all these deformations simultaneously. The method herein proposed was devised to simultaneously estimate translation, compression, stretching and shearing of the arterial wall in ultrasound B-mode image sequences representing the carotid artery longitudinal section. Salient blob-like patterns, called key points, are automatically detected in each frame and matched between successive frames. A robust estimator based on an affine transformation model is then used to assess frame-to-frame motion explaining at best the key-point matches and to reject outliers. Realistic simulated image sequences were used to evaluate the accuracy and robustness of the method against ground truth. The method was also visually assessed on clinical image sequences, for which true deformations are unknown.

Published
2021

18. Reconsidering adsorption in hemodialysis: is it just an epiphenomenon? A narrative review

Author

Fitsum Guebre-Egziabher, Laurent Juillard, Nans Florens, 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), and ROSSI, Sabine

Subjects
Dialysis adequacy, medicine.medical_treatment, 030232 urology & nephrology, Hemodiafiltration, 030204 cardiovascular system & hematology, Dialysis membrane, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Dialysis tubing, Hydrophobic effect, 03 medical and health sciences, 0302 clinical medicine, Adsorption, Renal Dialysis, Humans, Medicine, Renal replacement therapy, business.industry, Membranes, Artificial, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Membrane, Nephrology, Hemodialysis, Biophysics, Kidney Failure, Chronic, business, Dialysis (biochemistry)
Abstract

International audience; Since the first attempt at extracorporeal renal replacement therapy, renal replacement therapy has been constantly improved. In the field of hemodialysis, substantial efforts have been made to improve toxin removal and biocompatibility. The advent of hemodiafiltration (HDF) and, more recently, of mid cut-off membranes have contributed to management of patients with end-stage renal disease (ESRD). Although several uremic toxins have been discovered, we know little about the clinical impact of their clearance in hemodialysis patients. In addition, a great deal of progress has been made in the areas of filtration and diffusion, but the adsorptive properties of hemodialysis membranes remain under-studied. The mechanism of action of adsorption is based on the attraction between the polymer of the dialysis membrane and the solutes, through hydrophobic interactions, ionic or electrostatic forces, hydrogen bonds or van der Waals forces. Adsorption on the dialysis membrane depends on the membrane surface, pore size, structure and electric load. Its involvement in toxin removal and biocompatibility is significant, and is not just an epiphenomenon. Diffusive and convective properties cannot be improved indefinitely and high permeability membranes, despite their high performance in the clearance of many toxins, have several limitations for long-term use in hemodialysis. This review will discuss why adsorption should be reconsidered and better characterized to improve efficiency and adequacy of dialysis.

Published
2021

19. 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

20. Predictors of Outcome After Mechanical Thrombectomy in Stroke Patients Aged ≥85 Years

Author

Céline Odier, Julie Haesebaert, Norbert Nighoghossian, Omer Eker, Marlène Lapierre, Laura C. Gioia, Alexandre Y Poppe, Jean Raymond, Marielle Buisson, Walid Alesefir, Nicole Daneault, Grégory Jacquin, Daniel Roy, Yan Deschaintre, Christian Stapf, Yves Berthezène, Dana Iancu, Alain Weill, Fatine Karkri, Laurent Derex, Research on Healthcare Performance (RESHAPE - Inserm U1290 - UCBL1), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Service de neuroradiologie [Lyon], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (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), 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], Direction générale (DG), Centre national du machinisme agricole, du génie rural, des eaux et forêts (CEMAGREF), 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), CarMeN, laboratoire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon

Subjects
medicine.medical_specialty, Stroke patient, [SDV]Life Sciences [q-bio], medicine.medical_treatment, 030204 cardiovascular system & hematology, Logistic regression, Brain Ischemia, 03 medical and health sciences, Elderly, 0302 clinical medicine, Modified Rankin Scale, Internal medicine, medicine, Humans, Aged, Retrospective Studies, Thrombectomy, Aged, 80 and over, Ischemic stroke, business.industry, General Medicine, Thrombolysis, Odds ratio, 3. Good health, Stroke, [SDV] Life Sciences [q-bio], Mechanical thrombectomy, Treatment Outcome, Neurology, Reperfusion, Cohort, Neurology (clinical), business, Lower mortality, 030217 neurology & neurosurgery
Abstract

Background:The effectiveness of mechanical thrombectomy (MT) in elderly stroke patients remains debated. We aimed to describe outcomes and their predictors in a cohort of patients aged ≥ 85 years treated with MT.Methods:Data from consecutive patients aged ≥ 85 years undergoing MT at two stroke centers between January 2016 and November 2019 were reviewed. Admission National Institutes of Health Stroke Scale (NIHSS), pre-stroke, and 3-month modified Rankin scale (mRS) were collected. Successful recanalization was defined as modified thrombolysis in cerebral ischemia score ≥ 2b. Good outcome was defined as mRS 0–3 or equal to pre-stroke mRS at 3 months.Results:Of 151 included patients, successful recanalization was achieved in 74.2%. At 3 months, 44.7% of patients had a good outcome and 39% had died. Any intracranial hemorrhage (ICH) and symptomatic ICH occurred in 20.3% and 3.6%, respectively. Logistic regression analysis identified lower pre-stroke mRS score (adjusted odds ratio [aOR], 0.52; 95% CI, 0.36–0.76), lower admission NIHSS score (aOR, 0.90; 95% CI, 0.83–0.97), successful recanalization (aOR, 3.65; 95% CI, 1.32–10.09), and absence of ICH on follow-up imaging (aOR, 0.42; 95% CI, 0.08–0.75), to be independent predictors of good outcome. Patients with successful recanalization had a higher proportion of good outcome (45.3% vs 34.3%, p = 0.013) and lower mortality at 3 months (35.8% vs 48.6%, p = 0.006) compared to patients with unsuccessful recanalization.Conclusions:Among patients aged ≥ 85 years, successful recanalization with MT is relatively common and associated with better 3-month outcome and lower mortality than failed recanalization. Attempting to achieve recanalization in elderly patients using MT appears reasonable.

Published
2021

21. 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

22. Innovative approaches in CNS drug discovery

Author

Luc Zimmer, Mathieu Charvériat, Vincent Lafon, Franck Mouthon, Theranexus [Lyon], Insiliance, Hospices Civils de Lyon (HCL), Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), 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
Big Data, medicine.medical_specialty, Neurology, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Big data, 030226 pharmacology & pharmacy, 03 medical and health sciences, Neuropharmacology, 0302 clinical medicine, Artificial Intelligence, medicine, Animals, Humans, Pharmacology (medical), Intensive care medicine, Drug discovery, business.industry, Translational, Biomarker, 3. Good health, Central nervous system, Therapeutic Area, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], business, Central Nervous System Agents
Abstract

International audience; Central nervous system disorders remain the leading causes of mortality and morbidity worldwide, affecting more than 1 billion patients. This therapeutic area suffers from high unmet medical needs and the search for innovative approaches to identify therapeutic strategies is urgent in the field. This review will first cover the challenges and opportunities of drug discovery in neurology, and then as well as the new models, such as human model stem cells and animal models under development in the field. In addition, innovative and translational neuroimaging techniques will be discussed, as the use of big data and artificial intelligence to discovery new drugs in neurological and neuropsychiatric disorders.

Published
2021

23. 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

24. 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

25. 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

26. Material Decomposition in Spectral CT Using Deep Learning: A Sim2Real Transfer Approach

Author

Abascal, Juan F P J, Abascal, Juan Fpj, Ducros, Nicolas, Pronina, Valeriya, Rit, Simon, Rodesch, Pierre-Antoine, Broussaud, Thomas, Bussod, Suzanne, Douek, Philippe, Hauptmann, Andreas, Arridge, Simon, PEYRIN, Françoise, 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), and Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
General Computer Science, Computer science, Computed tomography, 02 engineering and technology, Iterative reconstruction, transfer learning, Regularization (mathematics), Convolutional neural network, 030218 nuclear medicine & medical imaging, Spectral CT, 03 medical and health sciences, 0302 clinical medicine, [INFO.INFO-LG]Computer Science [cs]/Machine Learning [cs.LG], [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, 0202 electrical engineering, electronic engineering, information engineering, medicine, General Materials Science, Electrical and Electronic Engineering, medicine.diagnostic_test, business.industry, Deep learning, General Engineering, deep learning, Experimental data, Decomposition, Nonlinear system, inverse problem, 020201 artificial intelligence & image processing, lcsh:Electrical engineering. Electronics. Nuclear engineering, Artificial intelligence, business, lcsh:TK1-9971, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Algorithm
Abstract

International audience; The state-of-the art for solving the nonlinear material decomposition problem in spectral computed tomogra-phy is based on variational methods, but these are computationally slow and critically depend on the particular choice of the regularization functional. Convolutional neural networks have been proposed for addressing these issues. However, learning algorithms require large amounts of experimental data sets. We propose a deep learning strategy for solving the material decomposition problem based on a U-Net architecture and a Sim2Real transfer learning approach where the knowledge that we learn from synthetic data is transferred to a real-world scenario. In order for this approach to work, synthetic data must be realistic and representative of the experimental data. For this purpose, numerical phantoms are generated from human CT volumes of the KiTS19 Challenge dataset, segmented into specic materials (soft tissue and bone). These volumes are projected into sinogram space in order to simulate photon counting data, taking into account the energy response of the scanner. The network is trained to decompose the materials in the projection domain after which we apply any conventional tomographic method to reconstruct the dierent material volumes. The proposed decomposition method is compared to a regularized Gauss-Newton (RGN) method on synthetic data, experimental phantom data and human thorax data.

Published
2021

27. 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

28. 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

29. The effect of natriuretic C-type peptide and its change over time on mortality in patients on haemodialysis or haemodiafiltration

Author

Peter J. Blankestijn, Menso J. Nubé, Marinus A. van den Dorpel, Camiel L.M. de Roij van Zuijdewijn, Muriel P.C. Grooteman, Michiel L. Bots, Lieke H A van Gastel, Denis Fouque, Piet M. ter Wee, Internal medicine, ACS - Diabetes & metabolism, Nephrology, VU University medical center, Vrije Universiteit Amsterdam [Amsterdam] (VU), University Medical Center [Utrecht], Department of Internal Medicine [Rotterdam, The Netherlands] (ROTTERDAM - Med Int), Maasstad Hospital, 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), Maasstad Ziekenhuis = Maasstad Hospital, and CarMeN, laboratoire

Subjects
Change over time, medicine.medical_specialty, medicine.drug_class, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Population, 030232 urology & nephrology, haemodiafiltration, 030204 cardiovascular system & hematology, convection volume, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, end-stage kidney disease, medicine, Natriuretic peptide, In patient, AcademicSubjects/MED00340, education, Dialysis, Transplantation, education.field_of_study, Proportional hazards model, business.industry, Original Articles, mortality, [SDV] Life Sciences [q-bio], haemodialysis, Nephrology, Cohort, NTproCNP, Cardiology, Hemodialysis, business, C-type natriuretic peptide
Abstract

Background C-type natriuretic peptide (CNP) and its co-product N-terminal proCNP (NTproCNP) have been associated with beneficial effects on the cardiovascular system. In prevalent dialysis patients, however, a relation between NTproCNP and mortality has not yet been investigated. Furthermore, as a middle molecular weight substance, its concentration might be influenced by dialysis modality. Methods In a cohort of patients treated with haemodialysis (HD) or haemodiafiltration (HDF), levels of NTproCNP were measured at baseline and 6, 12, 24 and 36 months. The relation between serum NTproCNP and mortality and the relation between the 6-month rate of change of NTproCNP and mortality were analysed using Cox regression models. For the longitudinal analyses, linear mixed models were used. Results In total, 406 subjects were studied. The median baseline serum NTproCNP was 93 pmol/L and the median follow-up was 2.97 years. No relation between baseline NTproCNP or its rate of change over 6 months and mortality was found. NTproCNP levels remained stable in HD patients, whereas NTproCNP decreased significantly in HDF patients. The relative decline depended on the magnitude of the convection volume. Conclusions In our study, levels of NTproCNP appear strongly elevated in prevalent dialysis patients. Second, while NTproCNP remains unaltered in HD patients, its levels decline in individuals treated with HDF, with the decline dependent on the magnitude of the convection volume. Third, NTproCNP is not related to mortality in this population. Thus NTproCNP does not seem to be a useful marker for mortality risk in dialysis patients.

Published
2021

30. 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

31. Guidelines for the management of chronic spontaneous urticaria: recommendations supported by the Centre of Evidence of the French Society of Dermatology

Author

M.‐H. Jegou, Bernard Guillot, Marie Beylot-Barry, Annabel Maruani, Stéphane Munck, S. Mavoungou, Hélène Cornillier, Bruno Giraudeau, G. d’Acremont, B.‐N. Pham, Olivier Chosidow, A.‐P. Jonville‐Bera, F. Hacard, Service d'immunologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Université de Tours (UT), Université de Nantes (UN), MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Nice Sophia-Antipolis (UNSA), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Bordeaux [Bordeaux], Hôpital Henri Mondor, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université de Tours, and Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques

Subjects
medicine.medical_specialty, Urticaria, [SDV]Life Sciences [q-bio], MEDLINE, Disease, Dermatology, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Correspondence, Drug approval, Research Letter, Medicine, Humans, Chronic Urticaria, skin and connective tissue diseases, ComputingMilieux_MISCELLANEOUS, Reimbursement, Angioedema, business.industry, Research Letters, 3. Good health, Natural history, 030228 respiratory system, Chronic Disease, medicine.symptom, business
Abstract

Chronic spontaneous urticaria (CSU) is an inflammatory disease characterised by spontaneous wheals or angioedema for more than 6 weeks. The natural history of the disease is resolution within several months or years, and treatment is necessary to limit flares, reduce pruritus and improve quality of life (QoL). Numerous medical drugs are available, all having suspensive effects on CSU. International guidelines from the EAACI/GA(2) LEN/EDF/UNEV were published in 2018,1 but practice remains heterogeneous, especially for CSU refractory to H1 antihistamines and regarding states' official drug approval and reimbursement policies.

Published
2021

32. 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

33. 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

34. 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

35. 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

36. Evaluation of GATE‐RTion (GATE/Geant4) Monte Carlo simulation settings for proton pencil beam scanning quality assurance

Author

Susanna Guatelli, Michael Taylor, David Boersma, A. Aitkenhead, Carla Winterhalter, L. Grevillot, Peter Sitch, A. Resch, Marie Vidal, David Sarrut, Karen J. Kirkby, Vladimir Ivanchenko, Ranald I Mackay, Lydia Maigne, A. Elia, Division of Cancer Sciences, University of Manchester [Manchester], The Christie NHS Foundation Trust, Austrian Center for Mediacl Innovation and Technology [Wiener Neustadt] (ACMIT), Austrian Center for Mediacl Innovation and Technology, EBG MedAustron GmbH, Centre for Medical Radiation Physics, University of Wollongong [Australia], Laboratoire de Physique de Clermont (LPC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), European Organization for Nuclear Research (CERN), Tomsk State University [Tomsk], Medizinische Universität Wien = Medical University of Vienna, Imagerie Tomographique et Radiothérapie, 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)-Université Claude Bernard Lyon 1 (UCBL), 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 de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), 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), and Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Monte Carlo method, Geant4, dose calculation, Imaging phantom, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Proton Therapy, Range (statistics), proton pencil beam scanning therapy, Humans, Computer Simulation, Radiometry, Pencil-beam scanning, Monte Carlo, Proton therapy, Physics, business.industry, Radiotherapy Planning, Computer-Assisted, Radiotherapy Dosage, General Medicine, GATE-RTion, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, Computational physics, 030220 oncology & carcinogenesis, Tomography, Protons, business, Monte Carlo Method, Quality assurance, Beam (structure)
Abstract

International audience; Purpose: Geant4 is a multi-purpose Monte Carlo simulation tool for modeling particle transport in matter. It provides a wide range of settings, which the user may optimize for their specific application. This study investigates GATE/Geant4 parameter settings for proton pencil beam scanning therapy.Methods: GATE8.1/Geant4.10.3.p03 (matching the versions used in GATE-RTion1.0) simulations were performed with a set of prebuilt Geant4 physics lists (QGSP_BIC, QGSP_BIC_EMY, QGSP_BIC_EMZ, QGSP_BIC_HP_EMZ), using 0.1mm-10mm as production cuts on secondary particles (electrons, photons, positrons) and varying the maximum step size of protons (0.1mm, 1mm, none). The results of the simulations were compared to measurement data taken during clinical patient specific quality assurance at The Christie NHS Foundation Trust pencil beam scanning proton therapy facility. Additionally, the influence of simulation settings was quantified in a realistic patient anatomy based on computer tomography (CT) scans.Results: When comparing the different physics lists, only the results (ranges in water) obtained with QGSP_BIC (G4EMStandardPhysics_Option0) depend on the maximum step size. There is clinically negligible difference in the target region when using High Precision neutron models (HP) for dose calculations. The EMZ electromagnetic constructor provides a closer agreement (within 0.35 mm) to measured beam sizes in air, but yields up to 20% longer execution times compared to the EMY electromagnetic constructor (maximum beam size difference 0.79 mm). The impact of this on patient-specific quality assurance simulations is clinically negligible, with a 97% average 2%/2 mm gamma pass rate for both physics lists. However, when considering the CT-based patient model, dose deviations up to 2.4% are observed. Production cuts do not substantially influence dosimetric results in solid water, but lead to dose differences of up to 4.1% in the patient CT. Small (compared to voxel size) production cuts increase execution times by factors of 5 (solid water) and 2 (patient CT).Conclusions: Taking both efficiency and dose accuracy into account and considering voxel sizes with 2 mm linear size, the authors recommend the following Geant4 settings to simulate patient specific quality assurance measurements: No step limiter on proton tracks; production cuts of 1 mm for electrons, photons and positrons (in the phantom and range-shifter) and 10 mm (world); best agreement to measurement data was found for QGSP_BIC_EMZ reference physics list at the cost of 20% increased execution times compared to QGSP_BIC_EMY. For simulations considering the patient CT model, the following settings are recommended: No step limiter on proton tracks; production cuts of 1 mm for electrons, photons and positrons (phantom/range-shifter) and 10 mm (world) if the goal is to achieve sufficient dosimetric accuracy to ensure that a plan is clinically safe; or 0.1 mm (phantom/range-shifter) and 1 mm (world) if higher dosimetric accuracy is needed (increasing execution times by a factor of 2); most accurate results expected for QGSP_BIC_EMZ reference physics list, at the cost of 10-20% increased execution times compared to QGSP_BIC_EMY.

Published
2020

37. Carotid Wall Longitudinal Motion in Ultrasound Imaging: An Expert Consensus Review

Author

Didier Vray, Rytis Jurkonis, Aimilia Gastounioti, Zhifan Gao, André Sérusclat, Konstantina S. Nikita, Spyretta Golemati, Guillaume Zahnd, Tomi Laitinen, Fereshteh Yousefi Rizi, Maciej Orkisz, Heikki Yli-Ollila, Jason S. Au, Maureen J. MacDonald, Monika Makūnaitė, Hamid Behnam, Tiina M. Laitinen, Nassir Navab, University of Teheran, University of Waterloo [Waterloo], Kanta-Häme Central Hospital, Kuopio University Hospital, National and Kapodistrian University of Athens (NKUA), Kaunas University of Technology (KTU), 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), 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), Computer Aided Medical Procedures & Augmented Reality (CAMPAR), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), McMaster University [Hamilton, Ontario], Iran University of Science and Technology [Tehran] (IUST), National Sun Yat-Sen University (NSYSU), Perelman School of Medicine, University of Pennsylvania [Philadelphia], Imagerie Ultrasonore, Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), National Technical University of Athens [Athens] (NTUA), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
medicine.medical_specialty, Consensus, Acoustics and Ultrasonics, Arteriosclerosis, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Carotid arteries, Biophysics, 030204 cardiovascular system & hematology, Longitudinal motion, Motion estimation, Motion (physics), 030218 nuclear medicine & medical imaging, Vascular health, Motion, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Ultrasound, medicine, Humans, Radiology, Nuclear Medicine and imaging, In patient, Wall motion, Cardiovascular risk factors, Ultrasonography, Speckle tracking, Radiological and Ultrasound Technology, business.industry, Block matching, Expert consensus, Atherosclerosis, 3. Good health, Carotid Arteries, Practice Guidelines as Topic, Ultrasound imaging, business, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Carotid artery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Motion extracted from the carotid artery wall provides unique information for vascular health evaluation. Carotid artery longitudinal wall motion corresponds to the multiphasic arterial wall excursion in the direction parallel to blood flow during the cardiac cycle. While this motion phenomenon has been well characterized, there is a general lack of awareness regarding its implications for vascular health assessment or even basic vascular physiology. In the last decade, novel estimation strategies and clinical investigations have greatly advanced our understanding of the bi-axial behavior of the carotid artery, necessitating an up-to-date review to summarize and classify the published literature in collaboration with technical and clinical experts in the field. Within this review, the state-of-the-art methodologies for carotid wall motion estimation are described, and the observed relationships between longitudinal motion-derived indices and vascular health are reported. The vast number of studies describing the longitudinal motion pattern in plaque-free arteries, with its putative application to cardiovascular disease prediction, point to the need for characterizing the added value and applicability of longitudinal motion beyond established biomarkers. To this aim, the main purpose of this review was to provide a strong base of theoretical knowledge, together with a curated set of practical guidelines and recommendations for longitudinal motion estimation in patients, to foster future discoveries in the field, toward the integration of longitudinal motion in basic science as well as clinical practice.

Published
2020

38. 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

39. 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

40. 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

41. 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

42. Mycoplasma hyopneumoniae J elicits an antioxidant response and decreases the expression of ciliary genes in infected swine epithelial cells

Author

Scheila G. Mucha, Sophie Rome, Marie-France Sagot, Laurent Guyon, Mariana Galvão Ferrarini, Carol Moraga, Florence Tardy, Alex Di Genova, Arnaldo Zaha, Centro de Biotecnologia [Porto Alegre] (CBiot), Universidade Federal do Rio Grande do Sul [Porto Alegre] (UFRGS), Baobab, Département PEGASE [LBBE] (PEGASE), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Equipe de recherche européenne en algorithmique et biologie formelle et expérimentale (ERABLE), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Mycoplasmoses des Ruminants - UMR (MYCO), Université de Lyon-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-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), CAPES782/13European Research Council (ERC)[247073]10CAPES CAPES-Cofecub doctoral fellowship CAPES post-doctoral fellowship (CAPES-Biologia Computacional) 611 23038.010043/2013-02CONICYT BECAS CHILE DOCTORADO 2016/FOLIO 72170320, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL)

Subjects
0301 basic medicine, Swine, [SDV]Life Sciences [q-bio], lcsh:Medicine, Article, Antioxidants, 03 medical and health sciences, 0302 clinical medicine, Mycoplasma hyopneumoniae, Bacterial Proteins, Gene expression, microRNA, Animals, Cilia, RNA, Messenger, Transcriptomics, lcsh:Science, Gene, Pathogen, Transcription factor, Cells, Cultured, Regulation of gene expression, Multidisciplinary, biology, Gene Expression Profiling, lcsh:R, Bacteriology, Epithelial Cells, Pneumonia of Swine, Mycoplasmal, biology.organism_classification, 3. Good health, Cell biology, Gene expression profiling, MicroRNAs, 030104 developmental biology, Gene Expression Regulation, miRNAs, lcsh:Q, Pathogens, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], 030217 neurology & neurosurgery, Biomarkers
Abstract

Mycoplasma hyopneumoniae is the most costly pathogen for swine production. Although several studies have focused on the host-bacterium association, little is known about the changes in gene expression of swine cells upon infection. To improve our understanding of this interaction, we infected swine epithelial NPTr cells with M. hyopneumoniae strain J to identify differentially expressed mRNAs and miRNAs. The levels of 1,268 genes and 170 miRNAs were significantly modified post-infection. Up-regulated mRNAs were enriched in genes related to redox homeostasis and antioxidant defense, known to be regulated by the transcription factor NRF2 in related species. Down-regulated mRNAs were enriched in genes associated with cytoskeleton and ciliary functions. Bioinformatic analyses suggested a correlation between changes in miRNA and mRNA levels, since we detected down-regulation of miRNAs predicted to target antioxidant genes and up-regulation of miRNAs targeting ciliary and cytoskeleton genes. Interestingly, most down-regulated miRNAs were detected in exosome-like vesicles suggesting that M. hyopneumoniae infection induced a modification of the composition of NPTr-released vesicles. Taken together, our data indicate that M. hyopneumoniae elicits an antioxidant response induced by NRF2 in infected cells. In addition, we propose that ciliostasis caused by this pathogen is partially explained by the down-regulation of ciliary genes.

Published
2020

43. Place des tests immunitaires fonctionnels dans la prise en charge du risque infectieux et de la gestion des thérapies immunosuppressives chez les patients immunodéprimés non-VIH

Author

W. Mouton, Fabienne Venet, I. Durieu, Chloé Albert-Vega, Mathilde Boccard, Florence Ader, Karen Brengel-Pesce, Sophie Trouillet-Assant, 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), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Laboratoire Commun de Recherche Hospices Civils de Lyon – bioMérieux (Cancer Biomarkers Research Group), Hospices Civils de Lyon (HCL)-BIOMERIEUX, Virology and human respiratory Pathologies - Virology and human respiratory Pathologies (VirPath), 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), Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques / Pathophysiology of Injury-induced Immunosuppression (PI3), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Hôpital Edouard Herriot [CHU - HCL], Hôpital de la Croix-Rousse [CHU - HCL], 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), Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques - EA 7426 (PI3), 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), 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), and CCSD, Accord Elsevier

Subjects
[SDV]Life Sciences [q-bio], medicine.medical_treatment, chemical and pharmacologic phenomena, 030230 surgery, 03 medical and health sciences, 0302 clinical medicine, Immune system, Internal Medicine, medicine, Infectious risk, Transplantation, business.industry, Vaccination, Gastroenterology, Immunosuppression, Immunotherapy, biochemical phenomena, metabolism, and nutrition, Vaccine efficacy, Precision medicine, Risque infectieux, 3. Good health, [SDV] Life Sciences [q-bio], Immunomonitoring, Immunodépression, Immunology, bacteria, Monitoring immunitaire, business, Ex vivo, 030215 immunology
Abstract

International audience; The holistic approach of the human immune system is based on the study of its components collectively driving a functional response to an immunogenic stimulus. To appreciate a specific immune dysfunction, a condition is mimicked ex vivo and the immune response induced is assessed. The application field of such assays are broad and expanding, from the diagnosis of primary and secondary immunodeficiencies, immunotherapy for cancer to the management of patients at-risk for infections and vaccination. These assays are immune monitoring tools that may contribute to a personalised and precision medicine. The purpose of this review is to describe immune functional assays available in the setting of non-HIV acquired immune deficiency. First, we will address the use of theses assays in the diagnosis of opportunistic infections such as viral reactivation. Secondly, we will report the usefulness of these assays to assess vaccine efficacy and to manage immunosuppressive therapies.

Published
2020

44. 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

45. Spectral photon-counting CT imaging of colorectal peritoneal metastases: initial experience in rats

Author

Vahan Kepenekian, Philippe Douek, Pascal Rousset, Pierre-Emmanuel Bonnot, Loic Boussel, Salim Si-Mohamed, Arnaud Thivolet, Christophe Blanchet, Bodescot, Myriam, In Vivo Spectral Photon Counting CT Molecular Imaging in Cardio- and Neuro-Vascular Diseases - SPCCT - - H20202016-01-01 - 2019-12-31 - 668142 - VALID, Radiology Department [Lyon], Hospices Civils de Lyon (HCL), Ciblage thérapeutique en Oncologie (EA3738), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Université de Lyon, 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), Surgical Department [Lyon], Pathology Department [Lyon], 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), This work was supported by European Union Horizon 2020 grant No 668142, France Life Imaging (FLI)., European Project: 668142,H2020,H2020-PHC-2015-two-stage,SPCCT(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 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), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL)

Subjects
0301 basic medicine, Male, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Gadolinium, chemistry.chemical_element, Contrast Media, lcsh:Medicine, [SDV.CAN]Life Sciences [q-bio]/Cancer, Sensitivity and Specificity, Article, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, Distribution (pharmacology), Medicine, Animals, Cancer models, lcsh:Science, Peritoneal Neoplasms, Photons, Multidisciplinary, business.industry, Significant difference, Contrast resolution, lcsh:R, Rats, Inbred Strains, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Colorectal cancer, Photon counting, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Disease Models, Animal, 030104 developmental biology, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, chemistry, Preclinical research, Surgical oncology, Immunohistochemistry, Cancer imaging, lcsh:Q, Tomography, Ct imaging, business, Nuclear medicine, Colorectal Neoplasms, Tomography, X-Ray Computed, 030217 neurology & neurosurgery, Neoplasm Transplantation
Abstract

Computed tomography imaging plays a major role in the preoperative assessment of tumor burden by providing an accurate mapping of the distribution of peritoneal metastases (PM). Spectral Photon Counting Computed Tomography (SPCCT) is an innovative imaging modality that could overcome the current limitations of conventional CT, offering not only better spatial resolution but also better contrast resolution by allowing the discrimination of multiple contrast agents. Based on this capability, we tested the feasibility of SPCCT in the detection of PM at different time of tumor growth in 16 rats inoculated with CC531 cells using dual-contrast injection protocols in two compartments (i.e. intravenous iodine and intraperitoneal gadolinium or the reverse protocol), compared to surgery. For all peritoneal regions and for both protocols, sensitivity was 69%, specificity was 100% and accuracy was 80%, and the correlation with surgical exploration was strong (p = 0.97; p = 0.0001). No significant difference was found in terms of diagnostic performance, quality of peritoneal opacification or diagnostic quality between the 2 injection protocols. We also showed poor vascularization of peritoneal metastases by measuring low concentrations of contrast agent in the largest lesions using SPCCT, which was confirmed by immunohistochemical analyses. In conclusion, SPCCT using dual-contrast agent injection protocols in 2 compartments is a promising imaging modality to assess the extent of PM in a rat model.

Published
2020

46. 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

47. 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

48. 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

49. Matrix Metalloproteinase-9 and Monocyte Chemoattractant Protein-1 Are Associated With Collateral Status in Acute Ischemic Stroke With Large Vessel Occlusion

Author

Camille Amaz, Nathan Mewton, Yves Berthezène, Claire Crola Da Silva, Marielle Buisson, Thomas Bochaton, Nathalie Dufay, Elodie Ong, Omer Eker, Alexandre Paccalet, Norbert Nighoghossian, Laurent Derex, Michel Ovize, Tae-Hee Cho, Laura Mechtouff, Stroke Department, Neurological Hospital, 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), Virologie et pathogenèse virale (VPV), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche et d'Application en Traitement de l'Image et du Signal (CREATIS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École Supérieure Chimie Physique Électronique de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), Imagerie et modélisation Vasculaires, Thoraciques et Cérébrales (MOTIVATE), 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), Neuroradiology Department, Neurological Hospital, Department of Cardiology, and Imagerie Tomographique et Radiothérapie

Subjects
Monocyte Chemoattractant Proteins, medicine.medical_specialty, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, digital subtraction angiography, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, collateral circulation, Acute ischemic stroke, brain edema, Advanced and Specialized Nursing, medicine.diagnostic_test, business.industry, Matrix metalloproteinase 9, Digital subtraction angiography, Collateral circulation, Inflammatory biomarkers, Cardiology, matrix metalloproteinase 9, Neurology (clinical), monocyte chemoattractant proteins, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery, Large vessel occlusion, Monocyte chemoattractant protein
Abstract

Background and Purpose: In ischemic stroke, inflammatory status may condition the development of collateral circulation. Here we assessed the relationship between systemic inflammatory biomarkers and collateral status in large vessel occlusion before mechanical thrombectomy. Methods: HIBISCUS-STROKE is a cohort study including acute ischemic stroke patients with large vessel occlusion treated with mechanical thrombectomy following admission magnetic resonance imaging. MMP-9 (matrix metalloproteinase-9) and MCP-1 (monocyte chemoattractant protein-1) were measured on blood sampling collected at admission. Collateral status was assessed on pretreatment Digital subtraction angiography and categorized into poor (Higashida score, 0–2) and good (Higashida score, 3–4). A multiple logistic regression model was performed to detect independent markers of good collateral status. Results: One hundred and twenty-two patients were included, of them 71 patients (58.2%) had a good collateral status. In univariate analysis, low MMP-9 levels ( P =0.01), high MCP-1 levels ( P P =0.046), a high diastolic blood pressure ( P =0.049), the absence of tandem occlusion ( P =0.046), a high Alberta Stroke Program Early CT Score ( P P P =0.02) and high MCP-1 levels ( P Conclusions: Low MMP-9 and high MCP-1 levels were associated with good pretreatment collateral status in patients with acute ischemic stroke with large vessel occlusion. These results might suggest a relationship between collateral status and inflammation.

Published
2020

50. 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

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