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1. Effect of Peg-IFN on the viral kinetics of patients with HDV infection treated with bulevirtide

Author: Selma El Messaoudi, Ségolène Brichler, Claire Fougerou-Leurent, Emmanuel Gordien, Athenaïs Gerber, Amal Kortebi, Garance Lagadic, Miroslava Subic-Levrero, Sophie Metivier, Stanislas Pol, Anne Minello, Vlad Ratziu, Vincent Leroy, Philippe Mathurin, Laurent Alric, Fatoumata Coulibaly, Jean-Michel Pawlotsky, Fabien Zoulim, Victor de Lédinghen, and Jérémie Guedj
Subjects: Viral kinetics, Hepatitis delta virus, Antiviral treatment, Peg-IFN, Bulevirtide, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Background & Aims: Bulevirtide is a first-in-class entry inhibitor antiviral treatment for chronic hepatitis D. The viral kinetics during bulevirtide therapy and the effect of combining bulevirtide with pegylated-interferon (Peg-IFN) are unknown. Methods: We used mathematical modelling to analyze the viral kinetics in two French observational cohorts of 183 patients receiving bulevirtide with or without Peg-IFN for 48 weeks. Results: The efficacy of bulevirtide in blocking cell infection was estimated to 90.3%, whereas Peg-IFN blocked viral production with an efficacy of 92.4%, albeit with large inter-individual variabilities. The addition of Peg-IFN to bulevirtide was associated with a more rapid virological decline, with a rate of virological response (>2 log of decline or undetectability) at week 48 of 86.9% (95% prediction interval [PI] = [79.7–95.0]), compared with 56.1% (95% PI = [46.4–66.7]) with bulevirtide only. The model was also used to predict the probability to achieve a cure of viral infection, with a rate of 8.8% (95% PI = [3.5–13.2]) with bulevirtide compared with 18.8% (95% PI = [11.6–29.0]) with bulevirtide + Peg-IFN. Mathematical modelling suggests that after 144 weeks of treatment, the rates of viral cure could be 42.1% (95% PI = [33.3–52.6]) with bulevirtide and 66.7% (95% PI = [56.5–76.8]) with bulevirtide + Peg-IFN. Conclusions: In this analysis of real-world data, Peg-IFN strongly enhanced the kinetics of viral decline in patients treated with bulevirtide. Randomized clinical trials are warranted to assess the virological and clinical benefit of this combination, and to identify predictors of poor response to treatment. Impact and implications: Bulevirtide has been approved for chronic HDV infection by regulatory agencies in Europe based on its good safety profile and rapid virological response after treatment initiation, but the optimal duration of treatment and the chance to achieve a sustained virological response remain unknown. The results presented in this study have a high impact for clinicians and investigators as they provide important knowledge on the long-term virological benefits of a combination of Peg-IFN and bulevirtide in patients with CHD. Clinical trials are now warranted to confirm those predictions.
Published: 2024
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2. Treatment with bulevirtide in HIV-infected patients with chronic hepatitis D: ANRS HD EP01 BuleDelta and compassionate cohort

Author: Victor de Lédinghen, Claire Fougerou-Leurent, Estelle Le Pabic, Stanislas Pol, Dulce Alfaiate, Karine Lacombe, Marie-Noëlle Hilleret, Caroline Lascoux-Combe, Anne Minello, Eric Billaud, Isabelle Rosa, Anne Gervais, Vlad Ratziu, Nathalie Ganne, Georges-Philippe Pageaux, Vincent Leroy, Véronique Loustaud-Ratti, Philippe Mathurin, Julie Chas, Caroline Jezequel, Sophie Métivier, Jérôme Dumortier, Jean-Pierre Arpurt, Tarik Asselah, Bruno Roche, Antonia Le Gruyer, Marc-Antoine Valantin, Caroline Scholtès, Emmanuel Gordien, Christelle Tual, Amel Kortebi, Fatoumata Coulibaly, Eric Rosenthal, Miroslava Subic-Levrero, Dominique Roulot, Fabien Zoulim, François Raffi, Laurent Alric, Patrick Miailhes, Albert Tran, Christiane Stern, Xavier Causse, Simona Tripon, Ghassan Riachi, Olivier Chazouillères, Armando Abergel, Louis d’Alteroche, Jérôme Gournay, Garance Lagadic, Patrizia Carrieri, Ségolène Brichler, Martin Siguier, Jessica Krause, Juliette Foucher, Souad Ben Ali, Magdalena Meszaros, Anne Varaut, and Valérie Canva
Subjects: Cirrhosis, HDV, HBV, Pegylated interferon, Hepatitis D, HDV RNA, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Background & Aims: In France, bulevirtide (BLV) became available in September 2019 through an early access program to treat patients with HDV. The aim of this analysis was to evaluate the efficacy and safety of BLV in patients with HIV and HDV coinfection. Methods: Patients received BLV 2 mg ± pegylated interferon-α (pegIFNα) according to the physician’s decision. The primary endpoint (per-protocol analysis) was the virological response rate at Week 48, defined as the proportion of patients with undetectable serum HDV RNA or a HDV RNA decline >2 log10 IU/ml from baseline. Results: The characteristics of the 38 patients were as follows: 28 male, mean age 47.7 years, and mean baseline HDV RNA viral load 5.7 ± 1.2 log10 IU/ml. Median HIV viral load and mean CD4 count were 32 (30–65) copies/ml and 566 ± 307/mm3, respectively. Eight patients stopped treatment before Week 48. At Week 48, 10 of 19 patients (52.6%) in the 2 mg BLV group and five of seven patients (71.4%) in the 2 mg BLV + pegIFNɑ group had reached virological response (no HDV RNA available in four patients). At Week 48, seven of 19 patients in the 2 mg BLV group and three of six patients in the 2 mg BLV + pegIFNɑ group had a combined response (virological response and normal alanine aminotransferase level). Conclusions: Adults living with HIV coinfected with HDV can be treated by BLV with a virological response in more than 50% of patients. The combination of BLV and pegIFNɑ showed a strong virological response. Impact and implications: Bulevirtide is the only EMA-approved drug for HDV treatment, and we showed that it can be used in adults living with HIV, with an overall good tolerability. Bulevirtide induces a virological response in more than 50% of patients, suggesting that bulevirtide should be considered as a first-line therapy in this specific population. Bulevirtide in combination with pegIFNα could be used in patients without pegIFNα contraindication. No specific drug–drug interaction is reported. Bulevirtide is the only EMA-approved drug for HDV treatment, and we showed that it can be used in adults living with HIV, with an overall good tolerability. Bulevirtide induces a virological response in more than 50% of patients, suggesting that bulevirtide should be considered as a first-line therapy in this specific population. Bulevirtide in combination with pegIFNα could be used in patients without pegIFNα contraindication. No specific drug–drug interaction is reported. Bulevirtide is the only EMA-approved drug for HDV treatment, and we showed that it can be used in adults living with HIV, with an overall good tolerability. Bulevirtide induces a virological response in more than 50% of patients, suggesting that bulevirtide should be considered as a first-line therapy in this specific population. Bulevirtide in combination with pegIFNα could be used in patients without pegIFNα contraindication. No specific drug–drug interaction is reported.
Published: 2024
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3. Management of pharmacovigilance during the COVID‐19 pandemic crisis by the safety department of an academic sponsor: Lessons learnt and challenges from the EU DisCoVeRy clinical trial

Author: Noémie Mercier, Drifa Belhadi, Aline DeChanet, Christelle Delmas, Juliette Saillard, Marina Dumousseaux, Soizic Le Mestre, Claire Fougerou‐Leurent, Assia Ferrane, Charles Burdet, Hélène Espérou, Florence Ader, Maya Hites, Nathan Peiffer‐Smadja, Julien Poissy, Claire Andrejak, José Artur Paiva, Evelina Tacconelli, Thérèse Staub, Richard Greil, Dominique Costagliola, France Mentre, Yazdan Yazdanpanah, Alpha Diallo, and the DisCoVeRy Safety Working group
Subjects: adverse event, COVID‐19, EU‐RESPONSE, pandemic crisis, pharmacovigilance, Therapeutics. Pharmacology, RM1-950
Abstract: Abstract The current COVID‐19 pandemic was an exceptional health situation, including for drug use. As there was no known effective drug for COVID‐19 at the beginning of the pandemic, different drug candidates were proposed. In this article, we present the challenges for an academic Safety Department to manage the global safety of a European trial during the pandemic. The National Institute for Health and Medical Research (Inserm) conducted a European multicenter, open‐label, randomized, controlled trial involving three repurposed and one‐in development drugs (lopinavir/ritonavir, IFN‐β1a, hydroxychloroquine, and remdesivir) in adults hospitalized with COVID‐19. From 25 March 2020 to 29 May 2020, the Inserm Safety Department had to manage 585 Serious Adverse Events (SAEs) initial notification and 396 follow‐up reports. The Inserm Safety Department's staff was mobilized to manage these SAEs and to report Expedited safety reports to the competent authorities within the legal timeframes. More than 500 queries were sent to the investigators due to a lack of or incoherent information on SAE forms. At the same time, the investigators were overwhelmed by the management of patients suffering from COVID‐19 infection. These particular conditions of missing data and lack of accurate description of adverse events made evaluation of the SAEs very difficult, particularly the assessment of the causal role of each investigational medicinal product. In parallel, working difficulties were accentuated by the national lockdown, frequent IT tool dysfunctions, delayed implementation of monitoring and the absence of automatic alerts for SAE form modification. Although COVID‐19 is a confounding factor per se, the delay in and quality of SAE form completion and the real‐time medical analysis by the Inserm Safety Department were major issues in the quick identification of potential safety signals. To conduct a high‐quality clinical trial and ensure patient safety, all stakeholders must take their roles and responsibilities.
Published: 2023
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4. Protocol for the DisCoVeRy trial: multicentre, adaptive, randomised trial of the safety and efficacy of treatments for COVID-19 in hospitalised adults

Author: Florence Ader, François-Xavier Lescure, Laetitia Moinot, Christelle Delmas, Hélène Espérou, Laurent Abel, Benjamin Leveau, Vinca Icard, Toni Alfaiate, Charles Burdet, France Mentré, Marion Schneider, Nathan Peiffer-Smadja, Julien Poissy, Lila Bouadma, Bruno Lina, Florence Morfin-Sherpa, Maude Bouscambert, Alexandre Gaymard, Gilles Peytavin, Jeremie Guedj, Cedric Laouenan, Drifa Belhadi, Axelle Dupont, Basma Basli, Anissa Chair, Samira Laribi, Julie Level, Marie-Capucine Tellier, Aline Dechanet, Dominique Costagliola, Sandrine Couffin-Cadiergues, Juliette Saillard, Claire Fougerou, Carole Cagnot, Soizic Le Mestre, Delphine Lebrasseur-Longuet, Ventzislava Petrov-Sanchez, Alpha Diallo, NoéMie Mercier, Sarah Tubiana, Benjamin Hamze, Ambre Gelley, Marion Noret, Eric D’Ortenzio, Oriane Puechal, and Caroline Semaille
Subjects: Medicine
Published: 2020
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5. Melatonin: From Pharmacokinetics to Clinical Use in Autism Spectrum Disorder

Author: Sébastien Lalanne, Claire Fougerou-Leurent, George M. Anderson, Carmen M. Schroder, Tali Nir, Sylvie Chokron, Richard Delorme, Bruno Claustrat, Eric Bellissant, Solenn Kermarrec, Patricia Franco, Laure Denis, and Sylvie Tordjman
Subjects: melatonin, circadian rhythm, pharmacokinetics, autism, autism spectrum disorder (ASD), autistic behavioral impairments, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract: The role of melatonin has been extensively investigated in pathophysiological conditions, including autism spectrum disorder (ASD). Reduced melatonin secretion has been reported in ASD and led to many clinical trials using immediate-release and prolonged-release oral formulations of melatonin. However, melatonin’s effects in ASD and the choice of formulation type require further study. Therapeutic benefits of melatonin on sleep disorders in ASD were observed, notably on sleep latency and sleep quality. Importantly, melatonin may also have a role in improving autistic behavioral impairments. The objective of this article is to review factors influencing treatment response and possible side effects following melatonin administration. It appears that the effects of exposure to exogenous melatonin are dependent on age, sex, route and time of administration, formulation type, dose, and association with several substances (such as tobacco or contraceptive pills). In addition, no major melatonin-related adverse effect was described in typical development and ASD. In conclusion, melatonin represents currently a well-validated and tolerated treatment for sleep disorders in children and adolescents with ASD. A more thorough consideration of factors influencing melatonin pharmacokinetics could illuminate the best use of melatonin in this population. Future studies are required in ASD to explore further dose-effect relationships of melatonin on sleep problems and autistic behavioral impairments.
Published: 2021
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6. Advances in the Research of Melatonin in Autism Spectrum Disorders: Literature Review and New Perspectives

Author: Guillaume Bronsard, Claire Fougerou, Michel Botbol, Sophie Ribardiere, Enas Lagdas, Solenn Kermarrec, Rémi Fagard, Olivier Schischmanoff, Nemat Jaafari, David Cohen, Marianne Barburoth, George M. Anderson, Imen Najjar, Eric Bellissant, Julie Vernay-Leconte, and Sylvie Tordjman
Subjects: melatonin, biological clocks, circadian rhythm, synchrony, autism spectrum disorders, social communication, stereotyped behaviors, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract: Abnormalities in melatonin physiology may be involved or closely linked to the pathophysiology and behavioral expression of autistic disorder, given its role in neurodevelopment and reports of sleep-wake rhythm disturbances, decreased nocturnal melatonin production, and beneficial therapeutic effects of melatonin in individuals with autism. In addition, melatonin, as a pineal gland hormone produced from serotonin, is of special interest in autistic disorder given reported alterations in central and peripheral serotonin neurobiology. More specifically, the role of melatonin in the ontogenetic establishment of circadian rhythms and the synchronization of peripheral oscillators opens interesting perspectives to ascertain better the mechanisms underlying the significant relationship found between lower nocturnal melatonin excretion and increased severity of autistic social communication impairments, especially for verbal communication and social imitative play. In this article, first we review the studies on melatonin levels and the treatment studies of melatonin in autistic disorder. Then, we discuss the relationships between melatonin and autistic behavioral impairments with regard to social communication (verbal and non-verbal communication, social interaction), and repetitive behaviors or interests with difficulties adapting to change. In conclusion, we emphasize that randomized clinical trials in autism spectrum disorders are warranted to establish potential therapeutic efficacy of melatonin for social communication impairments and stereotyped behaviors or interests.
Published: 2013
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7. Remdesivir for the treatment of hospitalised patients with COVID-19: final results from the DisCoVeRy randomised, controlled, open-label trial

Author: Florence Ader, Maude Bouscambert-Duchamp, Maya Hites, Nathan Peiffer-Smadja, Julien Poissy, Drifa Belhadi, Alpha Diallo, Christelle Delmas, Juliette Saillard, Aline Dechanet, Claire Fougerou, Minh-Patrick Lê, Gilles Peytavin, Noémie Mercier, Priyanka Velou, Sarah Tubiana, Xavier Lescure, Emmanuel Faure, Saad Nseir, Jean-Christophe Richard, Florent Wallet, François Goehringer, Benjamin Lefèvre, Antoine Kimmoun, François Raffi, Benjamin Gaborit, Jean Reignier, Jean-Philippe Lanoix, Claire Andrejak, Yoann Zerbib, Firouzé Bani-Sadr, Bruno Mourvilliers, François Danion, Yvon Ruch, Raphaël Clere-Jehl, Vincent Le Moing, Kada Klouche, Karine Lacombe, Guillaume Martin-Blondel, Fanny Vardon-Bounes, André Cabié, Jean-Marie Turmel, Lionel Piroth, Mathieu Blot, Élisabeth Botelho-Nevers, Amandine Gagneux-Brunon, Guillaume Thiery, François Bénézit, Rostane Gaci, Joy Mootien, Sébastien Gallien, Denis Garot, Kevin Bouiller, Loïc Epelboin, Stéphane Jauréguiberry, Alexandre Gaymard, Gil Verschelden, Sandra Braz, Joao Miguel Ferreira Ribeiro, Michael Joannidis, Thérèse Staub, Antoine Altdorfer, Richard Greil, Alexander Egle, Jérémie Guedj, Marion Noret, Roberto Roncon-Albuquerque, Jose-Artur Paiva, Bruno Lina, Dominique Costagliola, Yazdan Yazdanpanah, Charles Burdet, France Mentré, Hospices Civils de Lyon (HCL), Université libre de Bruxelles (ULB), 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, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), ANRS - Maladies infectieuses émergentes (ANRS - MIE), Institut National de la Santé et de la Recherche Médicale (INSERM), Pôle de Recherche Clinique [Paris] (PRC), Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Croix-Rousse [CHU - 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), Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), and Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie
Subjects: [SDV]Life Sciences [q-bio]
Abstract: BackgroundThe antiviral efficacy of remdesivir is still controversial. We aimed at evaluating its clinical effectiveness in hospitalised patients with COVID-19, with indication of oxygen and/or ventilator support. Following prior publication of preliminary results, here we present the final results after completion of data monitoring.MethodsIn this European multicentre, open-label, parallel-group, randomised, controlled trial (DisCoVeRy, NCT04315948; EudraCT2020-000936-23), participants were randomly allocated to receive usual standard of care (SoC) alone or in combination with remdesivir, lopinavir/ritonavir, lopinavir/ritonavir and IFN-β-1a, or hydroxychloroquine. Adult patients hospitalised with COVID-19 were eligible if they had clinical evidence of hypoxemic pneumonia, or required oxygen supplementation. Exclusion criteria included elevated liver enzyme, severe chronic kidney disease, any contra-indication to one of the studied treatments or their use in the 29 days before randomization, or use of ribavirin, as well as pregnancy or breast-feeding. Here, we report results for remdesivir + SoC versus SoC alone. Remdesivir was administered as 200 mg infusion on day 1, followed by once daily infusions of 100 mg up to 9 days, for a total duration of 10 days. It could be stopped after 5 days if the participant was discharged. Treatment assignation was performed via web-based block randomisation stratified on illness severity and administrative European region. The primary outcome was the clinical status at day 15 measured by the WHO 7-point ordinal scale, assessed in the intention-to-treat population.FindingsBetween March 22nd, 2020 and January 21st, 2021, 857 participants were randomised to one of the two arms in 5 European countries and 843 participants were included for the evaluation of remdesivir (control, n=423; remdesivir, n=420).At day 15, the distribution of the WHO ordinal scale was as follow in the remdesivir and control groups, respectively: Not hospitalized, no limitations on activities: 62/420 (14.8%) and 72/423 (17.0%); Not hospitalized, limitation on activities: 126/420 (30%) and 135/423 (31.9%); Hospitalized, not requiring supplemental oxygen: 56/420 (13.3%) and 31/423 (7.3%); Hospitalized, requiring supplemental oxygen: 75/420 (17.9%) and 65/423 (15.4%); Hospitalized, on non-invasive ventilation or high flow oxygen devices: 16/420 (3.8%) and 16/423 (3.8%); Hospitalized, on invasive mechanical ventilation or ECMO: 64/420 (15.2%) and 80/423 (18.9%); Death: 21/420 (5%) and 24/423 (5.7%). The difference between treatment groups was not statistically significant (OR for remdesivir, 1.02, 95% CI, 0.62 to 1.70, P=0.93). There was no significant difference in the occurrence of Serious Adverse Events between treatment groups (remdesivir, n=147/410, 35.9%, versus control, n=138/423, 32.6%, p=0.29).InterpretationRemdesivir use for the treatment of hospitalised patients with COVID-19 was not associated with clinical improvement at day 15.FundingEuropean Union Commission, French Ministry of Health, DIM One Health Île-de-France, REACTing, Fonds Erasme-COVID-ULB; Belgian Health Care Knowledge Centre (KCE), AGMT gGmbH, FEDER “European Regional Development Fund”, Portugal Ministry of Health, Portugal Agency for Clinical Research and Biomedical Innovation. Remdesivir was provided free of charge by Gilead.
Published: 2023

8. HCV eradication does not protect from fibrosis progression in patients with fibrosing cholestatic hepatitis after liver transplantation

Author: Audrey, Coilly, Mylène, Sebagh, Claire, Fougerou-Leurent, Georges-Philippe, Pageaux, Vincent, Leroy, Sylvie, Radenne, Christine, Silvain, Pascal, Lebray, Pauline, Houssel-Debry, Carole, Cagnot, Emilie, Rossignol, Hélène, Danjou, Aurélie, Veislinger, Didier, Samuel, Jean-Charles, Duclos-Vallée, Jérôme, Dumortier, Hôpital Paul Brousse, Physiopathologie et traitement des maladies du foie, Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Dynamique des systèmes d'adhérence et différenciation (DySAD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Albert Bonniot, Hospices Civils de Lyon, Departement de Neurologie (HCL), Laboratoire Inflammation, Tissus épithéliaux et Cytokines (LITEC), Université de Poitiers, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), Hospices Civils de Lyon (HCL), and The study was sponsored and funded by The National Agency for Research on AIDS and Viral Hepatitis (ANRS, France Recherche Nord&sud Sida-hiv Hépatites).
Subjects: Liver Cirrhosis, Liver transplantation, Hepatology, Cholangitis, Fibrosing cholestatic hepatitis, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hepacivirus, Hepatitis C, Chronic, Antiviral Agents, Hepatitis C, Fibrosis, Treatment, Recurrence, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, HCV, Pathology, Humans, Retrospective Studies
Abstract: International audience; INTRODUCTION: Hepatitis C virus (HCV) may recur after liver transplantation (LT) in the severe form of fibrosing cholestatic hepatitis (FCH). The prognosis dramatically improved by the use of direct acting antivirals (DAAs). The aim of the present study was to describe the change in histological features of FCH after virological eradication. METHODS: From the ANRS CUPILT cohort we included 17 patients who presented FCH and at least two graft biopsies, one before DAA-treatment and one after. A single expert pathologist, blinded for clinical outcome, retrospectively confirmed the diagnosis of FCH and progression of fibrosis. RESULTS: Diagnosis of FCH was made after a median [IQR] 6.0 [3.1-11.8] months after LT, and the median interval between diagnosis and onset of treatment was 1.2 [0.7-6.1] months. The rate of viral eradication was 94.1%. The median delay between the pre-treatment and the treatment biopsies was 12.5 [11.1-20.0] months. Between the end of treatment and the second biopsy, the delay was 5.3 [0.6-7.4] months. Fibrosis stage worsened in 10 patients (58.8%); 6 patients had cirrhosis (35.3%). Chronic rejection appeared in 4 (23.5%) patients. CONCLUSION: Our results suggest that, despite viral eradication in patients presenting FCH after LT, fibrosis progression was observed in half of patients. This should encourage monitoring fibrosis progression despite HCV cure.
Published: 2022

9. Enquête sur la certification aux bonnes pratiques cliniques en recherche académique

Author: Elodie Labourdette, Mariella Le Saux, Sabrina Nekmouche, Véronique Lorre, Jimmy Chesnais, Céline Joumard, Claire Fougerou-Leurent, Eric Bellissant, Aurelie Veislinger, Carole Marie, Catherine Bellot, Loïc Fin, Nathalie Alleton, and Bruno Laviolle
Subjects: Protocol (science), medicine.medical_specialty, business.industry, education, Certification, Audit, Certificate, 030226 pharmacology & pharmacy, 3. Good health, Clinical trial, 03 medical and health sciences, 0302 clinical medicine, Clinical research, Quality standard, Family medicine, Good clinical practice, Medicine, Pharmacology (medical), business
Abstract: Good clinical practice (GCP) is an international ethical and scientific quality standard for the design, conduct, performance, monitoring, auditing, recording, analyses and reporting of clinical trials. Before the start of a clinical trial, investigators commit to perform the research in accordance with GCPs, regulatory dispositions and protocol. The sponsors are responsible for investigators' selection and for controlling their skills. Whereas industrial sponsors systematically require a certificate of GCP training, academic sponsors seem to be less demanding. We have carried out two surveys between April and June 2018. A first questionnaire was sent to the 40 French academic directions of clinical research and innovation in order to determine their requirements about the GCP training of the investigators participating in their trials. The second questionnaire was transmitted to physicians of the "Bretagne recherche clinique hospitaliere network": Rennes, Saint-Malo, Saint-Brieuc, Vannes, Lorient and Pontivy hospitals, in order to determine the GCP certification rate, and their needs in terms of clinical research training. Twenty-eight (70%) directions of clinical research answered the first survey, among which 18 (64%) required systematically the investigators' GCP certification in case of category 1 interventional studies. This rate decreased for category 2 (50%) and non-interventional category 3 (18%) studies. A total of 345 physicians answered the second survey, among which 263 (76%) had already been clinical trial investigators. However, only 29% of all physicians and 54% of those who had been principal investigator were certified for GCP training. These results support the need for large campaigns of GCP training in public hospitals.
Published: 2020

10. Bleeding and thrombotic events in patients with severe COVID-19 supported with extracorporeal membrane oxygenation: a nationwide cohort study

Author: Alexandre, Mansour, Erwan, Flecher, Matthieu, Schmidt, Bertrand, Rozec, Isabelle, Gouin-Thibault, Maxime, Esvan, Claire, Fougerou, Bruno, Levy, Alizée, Porto, James T, Ross, Marylou, Para, Sabrina, Manganiello, Guillaume, Lebreton, André, Vincentelli, Nicolas, Nesseler, and Yannick, Fedun
Subjects: Cohort Studies, Extracorporeal Membrane Oxygenation, Anticoagulants, COVID-19, Humans, Hemorrhage, Thrombosis, Intracranial Hemorrhages, Retrospective Studies
Abstract: To describe bleeding and thrombotic events and their risk factors in patients receiving extracorporeal membrane oxygenation (ECMO) for severe coronavirus disease 2019 (COVID-19) and to evaluate their impact on in-hospital mortality.The ECMOSARS registry included COVID-19 patients supported by ECMO in France. We analyzed all patients included up to March 31, 2022 without missing data regarding bleeding and thrombotic events. The association of bleeding and thrombotic events with in-hospital mortality and pre-ECMO variables was assessed using multivariable logistic regression models.Among 620 patients supported by ECMO, 29% had only bleeding events, 16% only thrombotic events and 20% both bleeding and thrombosis. Cannulation site (18% of patients), ear nose and throat (12%), pulmonary bleeding (9%) and intracranial hemorrhage (8%) were the most frequent bleeding types. Device-related thrombosis and pulmonary embolism/thrombosis accounted for most of thrombotic events. In-hospital mortality was 55.7%. Bleeding events were associated with in-hospital mortality (adjusted odds ratio (adjOR) = 2.91[1.94-4.4]) but not thrombotic events (adjOR = 1.02[0.68-1.53]). Intracranial hemorrhage was strongly associated with in-hospital mortality (adjOR = 13.5[4.4-41.5]). Ventilation duration before ECMO ≥ 7 days and length of ECMO support were associated with bleeding. Thrombosis-associated factors were fibrinogen ≥ 6 g/L and length of ECMO support.In a nationwide cohort of COVID-19 patients supported by ECMO, bleeding incidence was high and associated with mortality. Intracranial hemorrhage incidence was higher than reported for non-COVID patients and carried the highest risk of death. Thrombotic events were less frequent and not associated with mortality. Length of ECMO support was associated with a higher risk of both bleeding and thrombosis, supporting the development of strategies to minimize ECMO duration.
Published: 2022

11. Real life study of bulevirtide in chronic hepatitis delta: preliminary results of the ANRS HD EP01 BuleDelta prospective cohort

Author: Helene Fontaine, Claire Fougerou-Leurent, Emmanuel Gordien, Caroline Scholtes, Sophie Metivier, Victor de Lédinghen, Vlad Ratziu, Laurent Alric, Nathalie Ganne-Carrié, Veronique Loustaud-Ratti, Dominique Guyader, Vincent Leroy, Jérôme Dumortier, Karine Lacombe, Georges-Philippe Pageaux, Anne Minello Franza, Christelle Tual, Alain Renault, Estelle Le Pabic, Lucie Marchand, Dominique Roulot, Fabien Zoulim, AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Bordeaux [Bordeaux], Hôpital Avicenne [AP-HP], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), Hospices Civils de Lyon (HCL), and Jonchère, Laurent
Subjects: [SDV] Life Sciences [q-bio], Hepatology, [SDV]Life Sciences [q-bio]
Abstract: International audience; Real life study of bulevirtide in chronic hepatitis delta: preliminary results of the ANRS HD EP01 BuleDelta prospective cohort
Published: 2022

12. Final results of the DisCoVeRy trial of remdesivir for patients admitted to hospital with COVID-19

Author: Florence Ader, Maude Bouscambert-Duchamp, Maya Hites, Nathan Peiffer-Smadja, France Mentré, Charles Burdet, Jérôme Aboab, Hafid Ait-Oufella, Antoine Altdorfer, Claire Andrejak, Pascal Andreu, Laurent Argaud, Firouzé Bani-Sadr, Drifa Belhadi, Leila Belkhir, François Benezit, Marc Berna, Mathieu Blot, Elisabeth Botelho-Nevers, Lila Bouadma, Olivier Bouchaud, David Bougon, Kevin Bouiller, Fanny Bounes-Vardon, David Boutoille, Alexandre Boyer, Sandra Braz, Cédric Bruel, André Cabié, Emmanuel Canet, Charles Cazanave, Cyrille Chabartier, Catherine Chirouze, Raphaël Clere-Jehl, Dominique Costagliola, Sandrine Couffin-Cadièrgues, Johan Courjon, Flora Crockett, François Danion, Aline Dechanet, Agathe Delbove, Jean Dellamonica, Christelle Delmas, Alpha Diallo, Félix Djossou, Clément Dubost, Alexandre Duvignaud, Alexander Egle, Olivier Epaulard, Loïc Epelboin, Hélène Esperou, Murielle Fartoukh, Karine Faure, Emmanuel Faure, Joao-Miguel Ferreira Ribeiro, Tristan Ferry, Cécile Ficko, Samy Figueiredo, Claire Fougerou, Vincent Fraipont, Benjamin Gaborit, Rostane Gaci, Amandine Gagneux-Brunon, Sébastien Gallien, Denis Garot, Alexandre Gaymard, Guillaume Geri, Sébastien Gibot, François Goehringer, Marie Gousseff, Richard Greil, Didier Gruson, Jérémie Guedj, Yves Hansmann, Olivier Hinschberger, Stéphane Jaureguiberry, Vanessa Jeanmichel, Michael Joannidis, Solen Kerneis, Antoine Kimmoun, Kada Klouche, Marie Lachâtre, Karine Lacombe, Fabrice Laine, Bernd Lamprecht, Jean-Philippe Lanoix, Odile Launay, Bruno Laviolle, Minh-Patrick Lê, Vincent Le Moing, Jérôme Le Pavec, Yves Le Tulzo, Paul Le Turnier, David Lebeaux, Benjamin Lefevre, Sylvie Leroy, François-Xavier Lescure, Henry Lessire, Benjamin Leveau, Bruno Lina, Paul Loubet, Alain Makinson, Denis Malvy, Charles-Hugo Marquette, Guillaume Martin-Blondel, Martin Martinot, Julien Mayaux, Armand Mekontso-Dessap, Noémie Mercier, Ferhat Meziani, Jean-Paul Mira, Jean-Michel Molina, Xavier Monnet, Joy Mootien, Bruno Mourvillier, Bruno Mourvilliers, Marlène Murris-Espin, Jean-Christophe Navellou, Marion Noret, Saad Nseir, Walid Oulehri, José-Artur Paiva, Thomas Perpoint, Gilles Peytavin, Gilles Pialoux, Benoît Pilmis, Vincent Piriou, Lionel Piroth, Julien Poissy, Valérie Pourcher, Jean-Pierre Quenot, François Raffi, Jean Reignier, Jean Reuter, Matthieu Revest, Jean-Christophe Richard, Béatrice Riu-Poulenc, Céline Robert, Pierre-Alexandre Roger, Claire Roger, Roberto Roncon-Albuquerque, Elisabeth Rouveix-Nordon, Yvon Ruch, Nadia Saidani, Juliette Saillard, Naomi Sayre, Eric Senneville, Albert Sotto, Thérèse Staub, Francois Stefan, Charles Tacquard, Nicolas Terzi, Julien Textoris, Guillaume Thiery, Jean-François Timsit, Violaine Tolsma, Sarah Tubiana, Jean-Marie Turmel, Florent Valour, Fanny Vardon-Bounes, Priyanka Velou, Gil Verschelden, Florent Wallet, Guilhem Wattecamps, Yazdan Yazdanpanah, Yoann Zerbib, UCL - SSS/IREC/LTAP - Louvain Centre for Toxicology and Applied Pharmacology, and UCL - (SLuc) Service de médecine interne générale
Subjects: Hospitalization, Clinical Trials as Topic, Alanine, Infectious Diseases, COVID-19, Humans, Adenosine Monophosphate, COVID-19 Drug Treatment
Published: 2022

13. Remdesivir plus standard of care versus standard of care alone for the treatment of patients admitted to hospital with COVID-19 (DisCoVeRy): a phase 3, randomised, controlled, open-label trial

Author: Florence Ader, Maude Bouscambert-Duchamp, Maya Hites, Nathan Peiffer-Smadja, Julien Poissy, Drifa Belhadi, Alpha Diallo, Minh-Patrick Lê, Gilles Peytavin, Thérèse Staub, Richard Greil, Jérémie Guedj, Jose-Artur Paiva, Dominique Costagliola, Yazdan Yazdanpanah, Charles Burdet, France Mentré, Alexander Egle, Michael Joannidis, Bernd Lamprecht, Antoine Altdorfer, Leila Belkhir, Vincent Fraipont, Gil Verschelden, Jérôme Aboab, Hafid Ait-Oufella, Claire Andrejak, Pascal Andreu, Laurent Argaud, Firouzé Bani-Sadr, François Benezit, Mathieu Blot, Elisabeth Botelho-Nevers, Lila Bouadma, Olivier Bouchaud, David Bougon, Kevin Bouiller, Fanny Bounes-Vardon, David Boutoille, Alexandre Boyer, Cédric Bruel, André Cabié, Emmanuel Canet, Charles Cazanave, Cyrille Chabartier, Catherine Chirouze, Raphaël Clere-Jehl, Johan Courjon, Flora Crockett, François Danion, Agathe Delbove, Jean Dellamonica, Félix Djossou, Clément Dubost, Alexandre Duvignaud, Olivier Epaulard, Loïc Epelboin, Murielle Fartoukh, Karine Faure, Emmanuel Faure, Tristan Ferry, Cécile Ficko, Samy Figueiredo, Benjamin Gaborit, Rostane Gaci, Amandine Gagneux-Brunon, Sébastien Gallien, Denis Garot, Guillaume Geri, Sébastien Gibot, François Goehringer, Marie Gousseff, Didier Gruson, Yves Hansmann, Olivier Hinschberger, Stéphane Jaureguiberry, Vanessa Jeanmichel, Solen Kerneis, Antoine Kimmoun, Kada Klouche, Marie Lachâtre, Karine Lacombe, Fabrice Laine, Jean-Philippe Lanoix, Odile Launay, Bruno Laviolle, Vincent Le Moing, Jérôme Le Pavec, Yves Le Tulzo, Paul Le Turnier, David Lebeaux, Benjamin Lefevre, Sylvie Leroy, François-Xavier Lescure, Henry Lessire, Benjamin Leveau, Paul Loubet, Alain Makinson, Denis Malvy, Charles-Hugo Marquette, Guillaume Martin-Blondel, Martin Martinot, Julien Mayaux, Armand Mekontso-Dessap, Ferhat Meziani, Jean-Paul Mira, Jean-Michel Molina, Xavier Monnet, Joy Mootien, Bruno Mourvillier, Marlène Murris-Espin, Jean-Christophe Navellou, Saad Nseir, Walid Oulehri, Thomas Perpoint, Gilles Pialoux, Benoît Pilmis, Vincent Piriou, Lionel Piroth, Valérie Pourcher, Jean-Pierre Quenot, François Raffi, Jean Reignier, Matthieu Revest, Jean-Christophe Richard, Béatrice Riu-Poulenc, Céline Robert, Pierre-Alexandre Roger, Claire Roger, Elisabeth Rouveix-Nordon, Yvon Ruch, Nadia Saidani, Naomi Sayre, Eric Senneville, Albert Sotto, Francois Stefan, Charles Tacquard, Nicolas Terzi, Julien Textoris, Guillaume Thiery, Jean-François Timsit, Violaine Tolsma, Jean-Marie Turmel, Florent Valour, Florent Wallet, Guilhem Wattecamps, Yoann Zerbib, Marc Berna, Jean Reuter, Sandra Braz, Joao-Miguel Ferreira Ribeiro, José-Artur Paiva, Roberto Roncon-Albuquerque, Alexandre Gaymard, Bruno Lina, Sarah Tubiana, Sandrine Couffin-Cadièrgues, Hélène Esperou, Aline Dechanet, Christelle Delmas, Claire Fougerou, Noémie Mercier, Marion Noret, Juliette Saillard, Priyanka Velou, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Internal Medicine, Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université libre de Bruxelles (ULB), 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, Imperial College London, Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), ANRS - Maladies infectieuses émergentes (ANRS - MIE), Institut National de la Santé et de la Recherche Médicale (INSERM), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier de Luxembourg [Luxembourg] (CHL), Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Universidade do Porto = University of Porto, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), ARN régulateurs bactériens et médecine (BRM), Université de Rennes (UR)-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 ), 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), 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), European Union Commission, French Ministry of Health, Domaine d'intérêt majeur One Health Île-de-France, REACTing, Fonds Erasme-COVID-Université Libre de Bruxelles, Belgian Health Care Knowledge Centre, Austrian Group Medical Tumor, European Regional Development Fund, Portugal Ministry of Health, Portugal Agency for Clinical Research and Biomedical Innovation., Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-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 ), 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), UCL - SSS/IREC/LTAP - Louvain Centre for Toxicology and Applied Pharmacology, and UCL - (SLuc) Service de médecine interne générale
Subjects: Male, medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Population, 030204 cardiovascular system & hematology, Antiviral Agents, law.invention, 03 medical and health sciences, Extracorporeal Membrane Oxygenation, 0302 clinical medicine, Randomized controlled trial, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, law, Internal medicine, Humans, Medicine, media_common.cataloged_instance, 030212 general & internal medicine, European union, education, Contraindication, ComputingMilieux_MISCELLANEOUS, Aged, media_common, Mechanical ventilation, education.field_of_study, Alanine, business.industry, COVID-19, Standard of Care, Odds ratio, Articles, Middle Aged, Respiration, Artificial, Adenosine Monophosphate, COVID-19 Drug Treatment, 3. Good health, Europe, Hospitalization, Oxygen, Clinical trial, Infectious Diseases, Clinical research, Female, business
Abstract: Summary Background The antiviral efficacy of remdesivir against SARS-CoV-2 is still controversial. We aimed to evaluate the clinical efficacy of remdesivir plus standard of care compared with standard of care alone in patients admitted to hospital with COVID-19, with indication of oxygen or ventilator support. Methods DisCoVeRy was a phase 3, open-label, adaptive, multicentre, randomised, controlled trial conducted in 48 sites in Europe (France, Belgium, Austria, Portugal, Luxembourg). Adult patients (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and illness of any duration were eligible if they had clinical evidence of hypoxaemic pneumonia, or required oxygen supplementation. Exclusion criteria included elevated liver enzymes, severe chronic kidney disease, any contraindication to one of the studied treatments or their use in the 29 days before random assignment, or use of ribavirin, as well as pregnancy or breastfeeding. Participants were randomly assigned (1:1:1:1:1) to receive standard of care alone or in combination with remdesivir, lopinavir–ritonavir, lopinavir–ritonavir and interferon beta-1a, or hydroxychloroquine. Randomisation used computer-generated blocks of various sizes; it was stratified on severity of disease at inclusion and on European administrative region. Remdesivir was administered as 200 mg intravenous infusion on day 1, followed by once daily, 1-h infusions of 100 mg up to 9 days, for a total duration of 10 days. It could be stopped after 5 days if the participant was discharged. The primary outcome was the clinical status at day 15 measured by the WHO seven-point ordinal scale, assessed in the intention-to-treat population. Safety was assessed in the modified intention-to-treat population and was one of the secondary outcomes. This trial is registered with the European Clinical Trials Database, EudraCT2020-000936-23, and ClinicalTrials.gov, NCT04315948. Findings Between March 22, 2020, and Jan 21, 2021, 857 participants were enrolled and randomly assigned to remdesivir plus standard of care (n=429) or standard of care only (n=428). 15 participants were excluded from analysis in the remdesivir group, and ten in the control group. At day 15, the distribution of the WHO ordinal scale was: (1) not hospitalised, no limitations on activities (61 [15%] of 414 in the remdesivir group vs 73 [17%] of 418 in the control group); (2) not hospitalised, limitation on activities (129 [31%] vs 132 [32%]); (3) hospitalised, not requiring supplemental oxygen (50 [12%] vs 29 [7%]); (4) hospitalised, requiring supplemental oxygen (76 [18%] vs 67 [16%]); (5) hospitalised, on non-invasive ventilation or high flow oxygen devices (15 [4%] vs 14 [3%]); (6) hospitalised, on invasive mechanical ventilation or extracorporeal membrane oxygenation (62 [15%] vs 79 [19%]); (7) death (21 [5%] vs 24 [6%]). The difference between treatment groups was not significant (odds ratio 0·98 [95% CI 0·77–1·25]; p=0·85). There was no significant difference in the occurrence of serious adverse events between treatment groups (remdesivir, 135 [33%] of 406 vs control, 130 [31%] of 418; p=0·48). Three deaths (acute respiratory distress syndrome, bacterial infection, and hepatorenal syndrome) were considered related to remdesivir by the investigators, but only one by the sponsor's safety team (hepatorenal syndrome). Interpretation No clinical benefit was observed from the use of remdesivir in patients who were admitted to hospital for COVID-19, were symptomatic for more than 7 days, and required oxygen support. Funding European Union Commission, French Ministry of Health, Domaine d'interet majeur One Health Ile-de-France, REACTing, Fonds Erasme-COVID-Universite Libre de Bruxelles, Belgian Health Care Knowledge Centre, Austrian Group Medical Tumor, European Regional Development Fund, Portugal Ministry of Health, Portugal Agency for Clinical Research and Biomedical Innovation. Translation For the French translation of the abstract see Supplementary Materials section.
Published: 2021

14. Certification ISO 9001 d’un système de management qualité dans un centre d’investigation clinique

Author: Alain Renault, Eric Bellissant, Bruno Laviolle, Claire Fougerou-Leurent, Claire Laforest, and Jimmy Chesnais
Subjects: Engineering, Standardization, business.industry, media_common.quotation_subject, Certification, 030226 pharmacology & pharmacy, Clinical trial, 03 medical and health sciences, Engineering management, 0302 clinical medicine, Quality management system, Clinical investigation, Pharmacology (medical), Quality (business), Good practice, business, media_common
Abstract: Beyond the application of legal requirements, clinical trials must have a permanent approach of quality control. The clinical investigation centers (CICs) are academic structures of clinical research certified by the French National institute of health and medical research (Inserm) and whose functioning relies on recommendations of good practice. It is important to accompany this standardization of practices by the implementation of a quality management system. This article presents the process that enabled the CIC of Rennes to become certified ISO 9001 by French standards association (Afnor) certification in May, 2016. The application of the fundamental principles of the standard ISO 9001 in the domain of clinical research is approached. The problem of the perimeter for the certification and the related process mapping are exposed. The activities of methodology, management and analysis of clinical studies were chosen for the initial certification of the CIC of Rennes. The perspectives for the extension of the perimeter of certification are also approached at the end of article.
Published: 2018

15. 12 Weeks of a Ribavirin‐Free Sofosbuvir and Nonstructural Protein 5A Inhibitor Regimen Is Enough to Treat Recurrence of Hepatitis C After Liver Transplantation

Author: Audrey Coilly, Carole Cagnot, Pascal Lebray, Stéphane Chevaliez, Alpha Diallo, Victor de Lédinghen, Jean-Charles Duclos-Vallée, Danielle Botta-Fridlund, Claire Francoz, Camille Besch, Nassim Kamar, Christine Silvain, P. Perré, Albert Tran, Jérôme Dumortier, François Habersetzer, Claire Fougerou-Leurent, Aurelie Veislinger, Valérie Canva, Vincent Di Martino, Georges-Philippe Pageaux, Filomena Conti, Caroline Jezequel, Christophe Duvoux, Armando Abergel, Christophe Moreno, Sylvie Radenne, Maryline Debette-Gratien, H. Montialoux, Emilie Rossignol, Vincent Leroy, Louis d’Alteroche, and Pauline Houssel-Debry
Subjects: Liver Cirrhosis, Male, Sofosbuvir, medicine.medical_treatment, Viral Nonstructural Proteins, 030230 surgery, Liver transplantation, medicine.disease_cause, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, Belgium, Recurrence, Prospective Studies, 10. No inequality, education.field_of_study, Graft Survival, virus diseases, Hepatitis C, Middle Aged, Sciences bio-médicales et agricoles, Prognosis, 3. Good health, Treatment Outcome, Disease Progression, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, France, Viral load, medicine.drug, Adult, medicine.medical_specialty, Hepatitis C virus, Population, Drug Administration Schedule, 03 medical and health sciences, Internal medicine, Ribavirin, medicine, Humans, education, Aged, Dose-Response Relationship, Drug, Hepatology, business.industry, Hepatitis C, Chronic, medicine.disease, digestive system diseases, Liver Transplantation, Regimen, chemistry, business
Abstract: Sofosbuvir (SOF) combined with nonstructural protein 5A (NS5A) inhibitors has demonstrated its efficacy in treating a recurrence of hepatitis C virus (HCV) after liver transplantation (LT). However, the duration of treatment and need for ribavirin (RBV) remain unclear in this population. Our aim was to determine whether LT recipients could be treated with an SOF + NS5A inhibitor-based regimen without RBV for 12 weeks post-LT. Between October 2013 and December 2015, 699 LT recipients experiencing an HCV recurrence were enrolled in the multicenter ANRS CO23 CUPILT cohort. We selected patients receiving SOF and NS5A inhibitor ± RBV and followed for at least 12 weeks after treatment discontinuation. The primary efficacy endpoint was a sustained virological response 12 weeks after the end of treatment (SVR12). Among these 699 patients, 512 fulfilled the inclusion criteria. Their main characteristics were: 70.1% genotype 1, 18.2% genotype 3, 21.1% cirrhosis, and 34.4% previously treated patients. We identified four groups of patients according to their treatment and duration: SOF + NS5A without RBV for 12 (156 patients) or 24 (239 patients) weeks; SOF + NS5A + RBV for 12 (47 patients) or 24 (70 patients) weeks. SVR12 values reached 94.9%, 97.9%, 95.7%, and 92.9%, respectively (P = 0.14). Only 20 patients experienced a treatment failure. Under multivariate analysis, factors such as fibrosis stage, previous treatment, HCV genotype, and baseline HCV viral load did not influence SVR12 rates in the four groups (P = 0.21). Hematological adverse events (AEs) were more common in the RBV group: anemia (P < 0.0001) and blood transfusion (P = 0.0001). Conclusion: SOF + NS5A inhibitors without RBV for 12 weeks constituted reliable therapy for recurrent HCV post-LT with an excellent SVR12 whatever the fibrosis stage, HCV genotype, and previous HCV treatment. (Hepatology 2018; 00:000-000)., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2018

16. Melatonin: From Pharmacokinetics to Clinical Use in Autism Spectrum Disorder

Author: Solenn Kermarrec, Sylvie Tordjman, Richard Delorme, George M. Anderson, Sébastien Lalanne, Tali Nir, Laure Denis, Carmen M. Schröder, Eric Bellissant, Bruno Claustrat, Claire Fougerou-Leurent, Patricia Franco, Sylvie Chokron, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Yale School of Medicine [New Haven, Connecticut] (YSM), Institut des Neurosciences Cellulaires et Intégratives (INCI), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Centre Neurosciences intégratives et Cognition (INCC - UMR 8002), Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut cellule souche et cerveau (SBRI), Institut National de la Recherche Agronomique (INRA)-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 Guillaume Régnier [Rennes], 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), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Yale University School of Medicine, Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut cellule souche et cerveau (U846 Inserm - UCBL1), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA), 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: Male, Autism Spectrum Disorder, [SDV]Life Sciences [q-bio], Receptors, Melatonin, Administration, Oral, melatonin, Review, Bioinformatics, 030226 pharmacology & pharmacy, lcsh:Chemistry, 0302 clinical medicine, Child, lcsh:QH301-705.5, Spectroscopy, education.field_of_study, Tryptophan, autism spectrum disorder (ASD), autistic behavioral impairments, General Medicine, Sleep Latency, 3. Good health, Computer Science Applications, Sleep Disorders, Intrinsic, Tolerability, Autism spectrum disorder, Child, Preschool, Injections, Intravenous, autism spectrum disorder (ASD), Female, Seasons, analytical variability, pharmacokinetics, hormones, hormone substitutes, and hormone antagonists, medicine.drug, Adult, circadian rhythm, concentration-effect relationship, Serotonin, endocrine system, dose-response effect, Population, Biological Availability, autism, Catalysis, Inorganic Chemistry, Melatonin, 03 medical and health sciences, mental disorders, medicine, Humans, Circadian rhythm, Physical and Theoretical Chemistry, tolerability, education, Adverse effect, Saliva, Molecular Biology, business.industry, Organic Chemistry, Social Behavior Disorders, medicine.disease, Clinical trial, autistic behavioral impairments, lcsh:Biology (General), lcsh:QD1-999, Delayed-Action Preparations, Dietary Supplements, Autism, business, 030217 neurology & neurosurgery
Abstract: International audience; The role of melatonin has been extensively investigated in pathophysiological conditions, including autism spectrum disorder (ASD). Reduced melatonin secretion has been reported in ASD and led to many clinical trials using immediate-release and prolonged-release oral formulations of melatonin. However, melatonin’s effects in ASD and the choice of formulation type require further study. Therapeutic benefits of melatonin on sleep disorders in ASD were observed, notably on sleep latency and sleep quality. Importantly, melatonin may also have a role in improving autistic behavioral impairments. The objective of this article is to review factors influencing treatment response and possible side effects following melatonin administration. It appears that the effects of exposure to exogenous melatonin are dependent on age, sex, route and time of administration, formulation type, dose, and association with several substances (such as tobacco or contraceptive pills). In addition, no major melatonin-related adverse effect was described in typical development and ASD. In conclusion, melatonin represents currently a well-validated and tolerated treatment for sleep disorders in children and adolescents with ASD. A more thorough consideration of factors influencing melatonin pharmacokinetics could illuminate the best use of melatonin in this population. Future studies are required in ASD to explore further dose-effect relationships of melatonin on sleep problems and autistic behavioral impairments.
Published: 2021

17. Remdesivir for the Treatment of Hospitalised Patients with COVID-19 (DisCoVeRy): A Randomised, Controlled, Open-Label Trial

Author: Florence Ader, Maude Bouscambert-Duchamp, Maya Hites, Nathan Peiffer-Smadja, Julien Poissy, Drifa Belhadi, Alpha Diallo, Christelle Delmas, Juliette Saillard, Aline Dechanet, Claire Fougerou, Minh-Patrick Lê, Gilles Peytavin, Noémie Mercier, Priyanka Velou, Sarah Tubiana, Xavier Lescure, Emmanuel Faure, Saad Nseir, Jean-Christophe Richard, Florent Wallet, François Goehringer, Benjamin Lefèvre, Antoine Kimmoun, François Raffi, Bejamin Gaborit, Jean Reignier, Jean-Philippe Lanoix, Claire Andrejak, Yoann Zerbib, Firouzé Bani-Sadr, Bruno Mourvilliers, François Danion, Yvon Ruch, Raphaël Clere-Jehl, Vincent Le Moing, Kada Klouche, Karine Lacombe, Guillaume Martin-Blondel, Fanny Vardon-Bounes, André Cabié, Jean-Marie Turmel, Lionel Piroth, Mathieu Blot, Elisabeth Botelho-Nevers, Amandine Gagneux-Brunon, Guillaume Thiery, François Bénézit, Rostane Gaci, Joy Mootien, Sébastien Gallien, Denis Garot, Kevin Bouiller, Loïc Epelboin, Stéphane Jauréguiberry, Alexandre Gaymard, Gil Verschelden, Sandra Braz, Joao-Miguel Ferreira Ribeiro, Michael Joannidis, Thérèse Staub, Antoine Altdorfer, Richard Greil, Alexander Egle, Jérémie Guedj, Marion Noret, Roberto Roncon-Albuquerque Jr, Jose-Artur Paiva, Bruno Lina, Dominique Costagliola, Yazdan Yazdanpanah, Charles Burdet, France Mentré, Hospices Civils de Lyon (HCL), Laboratoire de Virologie [Lyon], Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Virpath-Grippe, de l'émergence au contrôle -- Virpath-Influenza, from emergence to control (Virpath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université libre de Bruxelles (ULB), 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, Imperial College London, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Département d'épidémiologie, biostatistique et recherche clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], ANRS France Recherche Nord & sud Sida-hiv hépatites, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut de Veille Sanitaire (INVS), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Faculté de Médecine Henri Warembourg - Université de Lille, 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), 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), CHU Amiens-Picardie, Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), and Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie
Subjects: education.field_of_study, medicine.medical_specialty, business.industry, Population, Declaration, Commission, Treatment and control groups, Informed consent, Family medicine, Health care, medicine, media_common.cataloged_instance, European union, education, business, Psychology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Declaration of Helsinki, media_common
Abstract: Background: The antiviral efficacy of remdesivir is still controversial. We aimed at evaluating its clinical effectiveness in patients with COVID-19 requiring oxygen and/or ventilator support. Methods: In this European multicentre, open-label, parallel-group, randomised, controlled trial in adults hospitalised with COVID-19 (DisCoVeRy, NCT04315948; EudraCT2020-000936-23), participants were randomly allocated to receive usual standard of care alone or in combination with intravenous remdesivir (200 mg on day 1, then 100 mg once-daily for 9 days or until discharge). Treatment assignation was performed via web-based randomisation stratified on illness severity and administrative European region. The primary outcome was the clinical status at day 15 measured by the WHO 7-point ordinal scale, assessed in the intention-to-treat population. Findings: Between March 22nd, 2020 and January 21st, 2021, 857 participants were randomised to one of the two arms in 5 European countries and 832 participants were included for the evaluation of remdesivir (control, n=418; remdesivir, n=414). There was no difference in the clinical status neither at day 15 between treatment groups (OR for remdesivir, 0.98, 95% CI, 0.77 to 1.25, P=0.85) nor at day 29. The proportion of deaths at day 28 was not significantly different between control (8.9%) and remdesivir (8.2%) treatment groups (OR for remdesivir, 0.93 95%CI 0.57 to 1.52, P=0.77). There was also no difference on SARS-CoV-2 viral kinetics (effect of remdesivir on viral load slope, -0.004 log10 cp/10,000 cells/day, 95% CI, -0.03 to 0.02, P=0.75). There was no significant difference in the occurrence of Serious Adverse Events between treatment groups. Interpretation: The use of remdesivir for the treatment of hospitalised patients with COVID-19 was not associated with clinical improvement at day 15 or day 29, nor with a reduction in mortality, nor with a reduction in SARS-CoV-2 RNA. Trial Registration: DisCoVeRy, NCT04315948; EudraCT2020-000936-23 Funding: European Union Commission, French Ministry of Health, DIM One Health Ile-de-France, REACTing, Fonds Erasme-COVID-ULB; Belgian Health Care Knowledge Centre (KCE) Declaration of Interests: Dr. Costagliola reports grants and personal fees from Janssen, personal fees from Gilead, outside the submitted work. Dr. Mentre reports grants from INSERM Reacting (French Government), grants from Ministry of Health (French Government), grants from European Commission, during the conduct of the study; grants from Sanofi, grants from Roche, outside the submitted work. Dr. Hites reports grants from The Belgian Center for Knowledge (KCE), grants from Fonds Erasme-COVID-ULB, during the conduct of the study; personal fees from Gilead, outside the submitted work. Dr. Mootien reports non-financial support from GILEAD, outside the submitted work. Dr. Gaborit reports non-financial support from Gilead, non- financial support from MSD, outside the submitted work. Dr. Botelho-Nevers reports other from Pfizer, other from Janssen, outside the submitted work. Dr. Lacombe reports personal fees and non-financial support from Gilead, personal fees and non-financial support from Janssen, personal fees and non-financial support from MSD, personal fees and non-financial support from ViiV Healthcare, personal fees and non-financial support from Abbvie, during the conduct of the study. Dr. Wallet reports personal fees and non-financial support from Jazz pharmaceuticals, personal fees and non-financial support from Novartis, personal fees and nonPage financial support from Kite-Gilead, outside the submitted work. Dr. Kimmoun reports personal fees from Aguettan, personal fees from Aspen, outside the submitted work. Dr. Thiery reports personal fees from AMGEN, outside the submitted work. Dr. Burdet reports personal fees from Da Volterra, personal fees from Mylan Pharmaceuticals, outside the submitted work. Dr. Poissy reports personal fees from Gilead for lectures, outside the submitted work. Dr. Goehringer reports personal fees from Gilead Sciences, non-financial support from Gilead Sciences, grants from Biomerieux, non-financial support from Pfizer, outside the submitted work. Dr. Peytavin reports personal fees from Gilead Sciences, personal fees from Merck France, personal fees from ViiV Healthcare, personal fees from TheraTechnologies, outside the submitted work. Dr. Danion reports personal fees from Gilead, outside the submitted work. Dr. Raffi reports personal fees from Gilead, personal fees from Janssen, personal fees from MSD, personal fees from Abbvie, personal fees from ViiV Healthcare, personal fees from Theratechnologies, personal fees from Pfizer, outside the submitted work. Dr. Gallien reports personal fees from Gilead, personal fees from Pfizer, personal fees from ViiV, personal fees from MSD, outside the submitted work; and has received consulting fee from Gilead in August 2020 to check the registration file of remdesivir for the French administration. Dr. Nseir reports personal fees from MSD, personal fees from Pfizer, personal fees from Gilead, personal fees from Biomerieux, personal fees from BioRad, outside the submitted work. Dr. Lefevre reports personal fees from Mylan, personal fees from Gilead, outside the submitted work. Dr. Guedj reports personal fees from Roche, outside the submitted work. Other authors have nothing to disclose. Ethics Approval Statement: The trial was approved by the Ethics Committee (CPP Ile-de-France-III, approval #20.03.06.51744), and is sponsored by the Institut national de la sante et de la recherche medicale (Inserm, France); it was conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from all included participants (or their legal representatives if unable to consent). The present analysis is based on the protocol v11.0 of December 12th, 2020.
Published: 2021

18. Comparison of the effect of direct-acting antiviral with and without ribavirin on cyclosporine and tacrolimus clearance values results from the ANRS CO23 CUPILT cohort

Author: Thibaut Gelé, Christophe Duvoux, Anne Marie Taburet, Didier Samuel, Carole Cagnot, Claire Laforest, Christophe Moreno, Valérie Canva, H. Danjou, Georges-Philippe Pageaux, Victor de Lédinghen, Danielle Botta-Fridlund, Nassim Kamar, Audrey Lavenu, Lauriane Goldwirt, Sylvie Radenne, Claire Fougerou-Leurent, Filomena Conti, François Durand, Aurélie Barrail-Tran, Vincent Leroy, Louis d’Alteroche, Jean-Charles Duclos-Vallée, Pauline Houssel-Debry, Audrey Coilly, Université Paris-Sud - Paris 11 (UP11), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), CHU Grenoble, Hôpital Claude Huriez [Lille], CHU Lille, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Marseille, Université libre de Bruxelles (ULB), ANRS France Recherche Nord & sud Sida-hiv hépatites, Physiopathologie et traitement des maladies du foie, Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Paul Brousse, Hôpital Lapeyronie [Montpellier] (CHU), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Agence Nationale de Recherches sur le Sida et les Hépatites Virales, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: Male, Pyrrolidines, Sofosbuvir, medicine.medical_treatment, [SDV]Life Sciences [q-bio], HIV Infections, Liver transplantation, Pharmacologie, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, Pharmacology (medical), Drug Interactions, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Imidazoles, Anemia, Valine, General Medicine, Hepatitis C, Middle Aged, 3. Good health, Cyclosporine, 030211 gastroenterology & hepatology, Drug Therapy, Combination, Female, Immunosuppressive Agents, medicine.drug, medicine.medical_specialty, Daclatasvir, Liver fibrosis, Anaemia, Antiviral Agents, Tacrolimus, 03 medical and health sciences, Internal medicine, Ribavirin, medicine, Humans, Aged, Pharmacology, business.industry, medicine.disease, Liver Transplantation, Calcineurin, Regimen, chemistry, Carbamates, business
Abstract: Purpose: Direct-acting antiviral agents have demonstrated their efficacy in treating HCV recurrence after liver transplantation and particularly the sofosbuvir/daclatasvir combination. Pharmacokinetic data on both calcineurin inhibitors and direct-acting antiviral exposure in liver transplant recipients remain sparse. Methods: Patients were enrolled from the ANRS CO23 CUPILT cohort. All patients treated with sofosbuvir/daclatasvir with or without ribavirin were included in this study when blood samples were available to estimate the clearance of immunosuppressive therapy before direct-acting antiviral initiation and during follow-up. Apparent tacrolimus and cyclosporine clearances were estimated from trough concentrations measured using validated quality control assays. Results: Sixty-seven mainly male patients (79%) were included, with a mean age of 57 years and mean MELD score of 8.2; 50 were on tacrolimus, 17 on cyclosporine. Ribavirin was combined with sofosbuvir/daclatasvir in 52% of patients. Cyclosporine clearance remained unchanged as well as tacrolimus clearance under the ribavirin-free regimen. Tacrolimus clearance increased 4 weeks after direct-acting antivirals and ribavirin initiation versus baseline (geometric mean ratio 1.81; 90% CI 1.30–2.52). Patients under ribavirin had a significantly higher fibrosis stage (> 2) (p = 0.02) and lower haemoglobin during direct-acting antiviral treatment (p = 0.02) which impacted tacrolimus measurements. Direct-acting antiviral exposure was within the expected range. Conclusion: Our study demonstrated that liver transplant patients with a recurrence of hepatitis C who are initiating ribavirin combined with a sofosbuvir-daclatasvir direct-acting antiviral regimen may be at risk of lower tacrolimus concentrations because of probable ribavirin-induced anaemia and higher fibrosis score, although there are no effects on cyclosporine levels. Trial registration: NCT 01944527., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2019

19. Direct-acting antiviral agent–based regimen for HCV recurrence after combined liver-kidney transplantation: Results from the ANRS CO23 CUPILT study

Author: Jérôme Dumortier, A. Rohel, Jean-Charles Duclos-Vallée, Christophe Duvoux, Vincent Di Martino, Christine Silvain, Sébastien Dharancy, Danielle Botta-Fridlund, Sylvie Radenne, Maryline Debette-Gratien, Nassim Kamar, Audrey Coilly, Vincent Leroy, Georges-Philippe Pageaux, Armand Abergel, Louis d’Alteroche, Emilie Rossignol, Claire Francoz, Pauline Houssel-Debry, P. Perré, Filomena Conti, Claire Fougerou-Leurent, François Habersetzer, Camille Besch, Christophe Moreno, H. Montialoux, Valérie Canva, Albert Tran, Didier Samuel, Victor de Lédinghen, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Paul Brousse, Physiopathologie et traitement des maladies du foie, Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Service d'Hépatologie, Hôpital Henri Mondor, AP-HP, Créteil, France., Hôpital Henri Mondor, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Physiopathologie Toulouse Purpan (CPTP), 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), Département de Gastroentérologie et hépatologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hépato-gastro-entérologie, Hôpital Huriez-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Département d'hépatologie, Service d'hépatologie, Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital de la Croix-Rousse [CHU - HCL], Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Chirurgie Digestive, Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Interactions Virus-Hôte et Maladies Hépatiques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Virologie, Chirurgie digestive et hépatobiliaire, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hépato-Gastro-Entérologie et Nutrition [CHU Limoges], CHU Limoges, ANRS France Recherche Nord & sud Sida-hiv hépatites, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Paul Brousse-Université Paris-Sud - Paris 11 (UP11), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Université de Limoges (UNILIM)-CHU Limoges, Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), 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 Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent
Subjects: Graft Rejection, Male, Sofosbuvir, [SDV]Life Sciences [q-bio], medicine.medical_treatment, kidney transplantation/nephrology, Hepacivirus, 030230 surgery, Liver transplantation, medicine.disease_cause, 0302 clinical medicine, Recurrence, Risk Factors, Immunology and Allergy, liver disease: infectious, Pharmacology (medical), Prospective Studies, Prospective cohort study, education.field_of_study, Graft Survival, Middle Aged, Prognosis, Hepatitis C, 3. Good health, [SDV] Life Sciences [q-bio], kidney failure/injury, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, medicine.drug, Adult, medicine.medical_specialty, infectious disease, Hepatitis C virus, Population, clinical research/practice, Antiviral Agents, 03 medical and health sciences, Internal medicine, medicine, Humans, Adverse effect, education, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Transplantation, business.industry, Kidney Transplantation, Liver Transplantation, Regimen, Immunology, infection and infectious agents - viral: hepatitis C, business, liver transplantation/hepatology, Follow-Up Studies
Abstract: International audience; Hepatitis C virus (HCV) infection is associated with reduced patient survival following combined liver-kidney transplantation (LKT). The aim of this study was to assess the efficacy and safety of second-generation direct-acting antivirals (DAAs) in this difficult-to-treat population. The ANRS CO23 "Compassionate use of Protease Inhibitors in Viral C Liver Transplantation" (CUPILT) study is a prospective cohort including transplant recipients with recurrent HCV infection treated with DAAs. The present work focused on recipients with recurrent infection following LKT. The study population included 23 patients. All patients received at least one NS5B inhibitor (sofosbuvir) in their antiviral regimen an average of 90 months after LKT. Ninety-six percent of recipients achieved a sustained virological response (SVR) at week 12 (SVR12). In terms of tolerance, 39% of recipients presented with at least one serious adverse event. None of the patients experienced acute rejection during therapy and there were no deaths during follow-up. The glomerular filtration rate (GFR) decreased significantly from baseline to the end of therapy. However, this study did not show that the decline in GFR persisted over time or that it was directly related to DAAs. The DAA-based regimen is well tolerated with excellent results in terms of efficacy. It will become the gold standard for the treatment of recurrent HCV following LKT.
Published: 2017

20. Sofosbuvir‐based treatment of hepatitis C with severe fibrosis (METAVIR F3/F4) after liver transplantation

Author: A. Rohel, Christophe Moreno, Jean-Charles Duclos-Vallée, Sylvie Radenne, Camille Besch, Armand Abergel, Nassim Kamar, Albert Tran, Georges-Philippe Pageaux, Pascal Lebray, Pauline Houssel-Debry, Valérie Canva, Claire Francoz, Danielle Botta-Fridlund, Jérôme Dumortier, Alpha Diallo, Vincent Leroy, Christophe Duvoux, Louis d’Alteroche, Claire Fougerou-Leurent, Audrey Coilly, Vincent Di Martino, Didier Samuel, Filomena Conti, Victor de Lédinghen, and Emilie Rossignol
Subjects: Compassionate Use Trials, Liver Cirrhosis, Male, Pyrrolidines, Cirrhosis, Sofosbuvir, medicine.medical_treatment, Hepacivirus, 030230 surgery, Liver transplantation, medicine.disease_cause, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, Belgium, Recurrence, Prospective Studies, Imidazoles, Valine, Hepatitis C, Middle Aged, 3. Good health, Treatment Outcome, Female, 030211 gastroenterology & hepatology, France, Immunosuppressive Agents, medicine.drug, Reoperation, medicine.medical_specialty, Daclatasvir, Genotype, Hepatitis C virus, Antiviral Agents, 03 medical and health sciences, Internal medicine, Ribavirin, medicine, Humans, Protease Inhibitors, Aged, Transplantation, Hepatology, business.industry, medicine.disease, Liver Transplantation, chemistry, Immunology, Surgery, Carbamates, business
Abstract: Recurrence of hepatitis C virus (HCV) after liver transplantation (LT) can rapidly lead to liver graft cirrhosis and, therefore, graft failure and retransplantation or death. The aim of the present study was to assess efficacy and tolerance of sofosbuvir (SOF)–based regimens for the treatment of HCV recurrence in patients with severe fibrosis after LT. The Compassionate Use of Protease Inhibitors in Viral C Liver Transplantation (CULPIT) study is a prospective multicenter cohort including patients with HCV recurrence following LT treated with second generation direct antivirals. The present study focused on patients included between October 2013 and November 2014 and diagnosed with HCV recurrence and liver graft extensive fibrosis (METAVIR F3/F4). A SOF-based regimen was administered to 125 patients fulfilling inclusion criteria. The median delay from LT was 95.9 ± 69.6 months. The characteristics of patients were as follows: mean age, 59.4 ± 9.0 years; 78.4% male; infected by HCV genotype 1: 78.2%, mean HCV RNA: 6.1 ± 1.0 log10 IU/mL. Eighty patients had failed previous post-LT antiviral therapy (64.0%) including triple therapy with first generation protease inhibitors in 19 (15.2%) patients. The main combination regimen was SOF/daclatasvir (73.6%). Ribavirin was used in 60 patients. Sustained virological response 12 weeks after treatment was 92.8% (on an intention-to-treat basis); 7 patients with virological failure were observed. Serious adverse events occurred in 25.6% of the patients during antiviral treatment. During antiviral treatment and follow-up, 3 patients were retransplanted and 4 patients died. In conclusion, SOF-based antiviral treatment shows very promising results in patients with HCV recurrence and severe fibrosis after LT. Liver Transplantation 22 1367–1378 2016 AASLD. © 2016 by the American Association for the Study of Liver Diseases
Published: 2016

21. Safety of sofosbuvir-based regimens after liver transplantation longitudinal assessment of renal function in the prospective ANRS CO23 CUPILT study

Author: Rodolphe Anty, Alpha Diallo, Vincent Leroy, L. D’Alteroche, Jean Charles Duclos-Vallée, Claire Fougerou-Leurent, Christophe Duvoux, Vincent L.M. Esnault, P. Perré, François Habersetzer, Audrey Coilly, Aurelie Veislinger, Nassim Kamar, V. Di Martino, Emilie Rossignol, Valérie Canva, Maryline Debette-Gratien, Carole Cagnot, François Durand, Didier Samuel, Clémence M. Canivet, Danielle Botta-Fridlund, H. Montialoux, V. de Ledinghen, Christine Silvain, Camille Besch, Jérôme Dumortier, Albert Tran, Guillaume Favre, Pauline Houssel-Debry, Georges Philippe Pageaux, S. Radenne, H. Danjou, Sébastien Dharancy, Fabio Conti, Pascal Lebray, Armando Abergel, Christophe Moreno, Centre Hospitalier Universitaire de Nice (CHU Nice), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Laboratoire de PhysioMédecine Moléculaire (LP2M), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Grenoble, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Toulouse [Toulouse], Hôpital Claude Huriez [Lille], CHU Lille, Hôpital Edouard Herriot [CHU - HCL], Service d'Hépato-Gastro-Entérologie [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), CHU Strasbourg, CHU Marseille, CHU Rouen, Normandie Université (NU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Interactions Virus-Hôte et Maladies Hépatiques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Virologie, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, CHU Limoges, ANRS France Recherche Nord & sud Sida-hiv hépatites, Hôpital Lapeyronie [Montpellier] (CHU), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: medicine.medical_specialty, Sofosbuvir, Hepatitis C virus, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Urology, Renal function, Hepacivirus, 030230 surgery, Liver transplantation, medicine.disease_cause, Kidney, Cohort Studies, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Recurrence, Ribavirin, Medicine, Humans, Pharmacology (medical), Longitudinal Studies, Prospective Studies, Renal Insufficiency, Chronic, Aged, Creatinine, Hepatology, business.industry, Gastroenterology, Middle Aged, Hepatitis C, 3. Good health, Liver Transplantation, medicine.anatomical_structure, chemistry, Cohort, 030211 gastroenterology & hepatology, Female, business, medicine.drug, Glomerular Filtration Rate
Abstract: International audience; Background In liver transplant recipients with hepatitis C virus recurrence, there is concern about renal safety of sofosbuvir-based regimens. Changes in serum creatinine or in the estimated glomerular filtration rate (eGFR) under treatment are used to look for possible renal toxicity. However, serum creatinine and eGFR are highly variable. Aim To analyse renal function trajectory with numerous assays of serum creatinine over a long period of time. Methods In a multicentre cohort of 139 patients, the eGFR was obtained from serum creatinine using the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation. Slopes of eGFR were defined as a change in eGFR during a period divided by time. Pre-treatment, on-treatment and post-treatment periods were 9 months, 3-9 months and 4.5 months. Interactions between eGFR slopes and the pre-treatment eGFR, use of ribavirin or mycophenolate mofetil, and stage of fibrosis were addressed. On-treatment eGFR slopes were separated in tertiles. Pre- and post-treatment eGFR slopes were compared globally and according to tertiles. Results The post-treatment eGFR slope was significantly better than pre-treatment eGFR slope (+0.18 (IQR -0.76 to +1.32) vs -0.11 (IQR -1.01 to +0.73) mL/min/1.73 m(2)/month, P=0.03) independently of the pre-treatment eGFR (P=0.99), ribavirin administration (P=0.26), mycophenolate mofetil administration (P=0.51) and stage of fibrosis (F3 and F4 vs lower stages, P=0.18; F4 vs lower stages, P=0.08; F4 Child-Pugh B and C vs lower stages, P=0.38). Tertiles of on-treatment eGFR slopes were -1.71 (IQR -2.54 to -1.48), -0.78 (IQR -1.03 to -0.36) and +0.75 (IQR +0.28 to +1.47) mL/min/1.73 m(2)/month. Pre- and post-treatment eGFR slopes were not significantly different according to tertiles (respectively, P=0.34, 0.08, 0.73). Conclusion The eGFR varies during treatment and gives a confusing picture of the renal safety of sofosbuvir-based regimens. In contrast, longitudinal assessment of the eGFR shows a rising trajectory over longer time, meaning that these therapies are safe for the kidneys in our cohort of liver transplant recipients.
Published: 2018

22. Efficacy, safety and patient-reported outcomes of ledipasvir/sofosbuvir in NS3/4A protease inhibitor-experienced individuals with hepatitis C virus genotype 1 and HIV coinfection with and without cirrhosis (ANRS HC31 SOFTRIH study)

Author: Isabelle Poizot-Martin, P. Perré, Stanislas Pol, Lionel Piroth, L Alric, Stéphanie Dominguez, Thierry Allegre, I. Amri, Yazdan Yazdanpanah, G.-P. Pageaux, M P Carrieri, Eric Billaud, Alissa Naqvi, Eric Bellissant, M Dupon, Marc-Antoine Valantin, Pierre-Marie Girard, Julie Chas, P de Truchis, Vincent Leroy, M. Bourlière, Philippe Morlat, Stéphane Chevaliez, E. Le Pabic, J.-M. Molina, Eric Rosenthal, F Raffi, S. Metivier, Claire Fougerou-Leurent, Hugues Aumaitre, Alain Renault, V. Jeantils, Fabienne Marcellin, François Bailly, Rodolphe Garraffo, Didier Neau, David Zucman, Jacques Reynes, A. Pailhé, Christelle Tual, Karine Lacombe, Laurent Cotte, Elina Teicher, Dominique Salmon-Ceron, Centre Hospitalier Universitaire de Nice (CHU Nice), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Université de Rennes 1 - Faculté de Médecine (UR1 Médecine), Université de Rennes (UR), ORS PACA, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Centre Hospitalier Saint Jean de Perpignan, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hospices Civils de Lyon (HCL), Centre hospitalier universitaire de Nantes (CHU Nantes), 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), Service de Maladies Infectieuses et Tropicales [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), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Bordeaux [Bordeaux], Centre Hospitalier du Pays d'Aix, Hôpital Raymond Poincaré [AP-HP], Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Tenon [AP-HP], Hôpital Cochin [AP-HP], Service Maladies infectieuses et tropicales [AP-HP Hôpital Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Service d'hépatologie médicale [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Gastro-entérologie [CHU Cochin], Hôpital Saint-Joseph [Marseille], Hôpital Foch [Suresnes], Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), AP-HP - Hôpital Bichat - Claude Bernard [Paris], ANRS France Recherche Nord & sud Sida-hiv hépatites, Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Agence Nationale de Recherches sur le Sida et les Hépatites Virales, Gilead Sciences, KARLI, Mélanie, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), CHU Toulouse [Toulouse], Université de Rennes - Faculté de Médecine (UR Médecine), Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Male, hepatitis C virus, Cirrhosis, ledipasvir, Sofosbuvir, Sustained Virologic Response, HIV Infections, Pilot Projects, Hepacivirus, medicine.disease_cause, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, Pegylated interferon, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Pharmacology (medical), 030212 general & internal medicine, treatment, Health Policy, virus diseases, Middle Aged, 3. Good health, Infectious Diseases, Treatment Outcome, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Coinfection, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 030211 gastroenterology & hepatology, Female, medicine.drug, Ledipasvir, medicine.medical_specialty, Genotype, Hepatitis C virus, sofosbuvir, Drug Administration Schedule, 03 medical and health sciences, Internal medicine, medicine, Humans, Protease inhibitor (pharmacology), Patient Reported Outcome Measures, Aged, Fluorenes, business.industry, Ribavirin, HIV, HIV Protease Inhibitors, Hepatitis C, Chronic, medicine.disease, Fibrosis, coinfection, chemistry, HIV-1, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Benzimidazoles, business
Abstract: International audience; Objectives - Studies evaluating the efficacy and safety of the fixed-dose combination ledipasvir (LDV)/sofosbuvir (SOF) in patients coinfected with HIV-1 and hepatitis C virus (HCV) have mainly included treatment-naïve patients without cirrhosis. We aimed to evaluate the efficacy and safety of this combination in treatment-experienced patients with and without cirrhosis.Methods - We conducted a multicentre, open-label, double-arm, nonrandomized study in patients coinfected with HIV-1 and HCV genotype 1 with and without cirrhosis, who had good viral suppression on their antiretroviral regimens. All patients were pretreated with a first-generation NS3/4A protease inhibitor (PI) plus pegylated interferon/ribavirin. Patients received a fixed-dose combination of LDV/SOF for 12 weeks, or for 24 weeks if cirrhosis was present. The primary endpoint was a sustained virological response (SVR) 12 weeks after the end of therapy. Secondary endpoints included safety, pharmacokinetics and patient-reported outcomes.Results - Of the 68 patients enrolled, 39.7% had cirrhosis. Sixty-five patients [95.6%; 95% confidence interval (CI): 87.6-99.1%; P < 0.0001] achieved an SVR, with similar rates of SVR in those with and without cirrhosis. Tolerance was satisfactory, with mainly grade 1 or 2 adverse events. Among patient-reported outcomes, only fatigue significantly decreased at the end of treatment compared with baseline [odds ratio (OR): 0.36; 95% CI: 0.14-0.96; P = 0.04]. Mean tenofovir area under the plasma concentration-time curve (AUC) at week 4 was high, with mean ± SD AUC variation between baseline and week 4 higher in cirrhotic than in noncirrhotic patients (3261.57 ± 1920.47 ng/mL vs. 1576.15 ± 911.97 ng/mL, respectively; P = 0.03). Mild proteinuria (54.4%), hypophosphataemia (50.0%), blood bicarbonate decrease (29.4%) and hypokalaemia (13.2%) were reported. The serum creatinine level was not modified.Conclusions - LDV/SOF provided a high SVR rate in PI-experienced subjects coinfected with HCV genotype 1 and HIV-1, including patients with cirrhosis.
Published: 2018

23. Sofosbuvir-Based Regimens in HIV/HCV Coinfected Patients after Liver Transplantation: Results from the ANRS CO23 CUPILT Study

Author: Didier Samuel, Audrey Coilly, Jérôme Dumortier, Vincent Leroy, Danielle Botta-Fridlund, Anne-Marie Taburet, P. Perré, A. Rohel, Aurelie Veislinger, Emilie Rossignol, Teresa Antonini, Valérie Canva, Pauline Houssel-Debry, Jean Charles Duclos-Vallée, Sylvie Radenne, Georges Philippe Pageaux, Alpha Diallo, Nassim Kamar, Claire Fougerou-Leurent, François Durand, V. de Ledinghen, Physiopathologie et traitement des maladies du foie, Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Dynamique des systèmes d'adhérence et différenciation (DySAD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), CHU Marseille, Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Foie, métabolismes et cancer, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-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 ), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Services de Maladies de l'Appareil Digestif, Hôpital Claude Huriez, Centre Hospitalier Universitaire de Lille, Lille, France, Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille, CHU Bordeaux [Bordeaux], ANRS France Recherche Nord & sud Sida-hiv hépatites, Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Lapeyronie [Montpellier] (CHU), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-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 Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Ledipasvir, Male, medicine.medical_specialty, Daclatasvir, Sofosbuvir, medicine.medical_treatment, Hepatitis C virus, [SDV]Life Sciences [q-bio], HIV Infections, Liver transplantation, medicine.disease_cause, Gastroenterology, Antiviral Agents, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, Humans, 030212 general & internal medicine, Transplantation, business.industry, Coinfection, Ribavirin, virus diseases, Hepatitis C, Middle Aged, medicine.disease, 3. Good health, Liver Transplantation, chemistry, Liver, 030211 gastroenterology & hepatology, Female, business, Viral load, medicine.drug
Abstract: Background A recurrence of hepatitis C virus (HCV) after liver transplantation affects survival in human immunodeficiency virus (HIV)/HCV coinfected patients. This study assessed the efficacy and safety of sofosbuvir (SOF)-based regimens in HIV/HCV coinfected patients after liver transplantation. Methods Twenty-nine HIV/HCV coinfected transplanted patients receiving tacrolimus-, cyclosporine-, or everolimus-based immunosuppressive therapy were enrolled in the Compassionate Use of Protease Inhibitors in Viral C Liver Transplantation cohort. Their antiviral treatment combined SOF, daclatasvir with or without ribavirin (n = 10/n = 6), or SOF, ledipasvir with or without ribavirin (n = 2/n = 11). Results The median delay between liver transplantation and treatment initiation was 37.5 months (interquartile range [IQR], 14.4-99.2). The breakdown of HCV genotypes was G1, 22 patients (75.9%); G3, 3 patients (10.3%); and G4, 4 patients (13.8%). The treatment indications were HCV recurrence (≥ F1 n = 23) or fibrosing cholestatic hepatitis (n = 6). Before starting SOF, the HCV viral load and CD4 count were 6.7 log 10 IU/mL (IQR, 5.9-7.2) and 342 cells/mm 3 (IQR, 172-483), respectively. At week 4, the HCV viral load was less than 15 IU/mL in 12 (42.9%) patients. The overall sustained virological response 12 was 96.6%. No significant drug-drug interactions were observed. Conclusions SOF-based treatment regimens produced excellent results in HIV/HCV coinfected patients after liver transplantation, suggesting an important change in their prognosis. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
Published: 2018

24. [ISO 9001certification of a quality management system in a clinical investigation center]

Author: Jimmy, Chesnais, Claire, Fougerou-Leurent, Claire, Laforest, Alain, Renault, Eric, Bellissant, and Bruno, Laviolle
Subjects: Quality Control, Clinical Trials as Topic, Biomedical Research, Certification, Quality Assurance, Health Care, Research Design, Academies and Institutes, Humans, France, Reference Standards, Societies, Medical
Abstract: Beyond the application of legal requirements, clinical trials must have a permanent approach of quality control. The clinical investigation centers (CICs) are academic structures of clinical research certified by the French National institute of health and medical research (Inserm) and whose functioning relies on recommendations of good practice. It is important to accompany this standardization of practices by the implementation of a quality management system. This article presents the process that enabled the CIC of Rennes to become certified ISO 9001 by French standards association (Afnor) certification in May, 2016. The application of the fundamental principles of the standard ISO 9001 in the domain of clinical research is approached. The problem of the perimeter for the certification and the related process mapping are exposed. The activities of methodology, management and analysis of clinical studies were chosen for the initial certification of the CIC of Rennes. The perspectives for the extension of the perimeter of certification are also approached at the end of article.
Published: 2017

25. Melatonin: Pharmacology, Functions and Therapeutic Benefits

Author: Annaëlle Charrier, Eric Bellissant, Claire Fougerou, Nemat Jaafari, Sylvie Tordjman, Richard Delorme, Sylvie Chokron, Service Psychiatrie de l'Enfant et de l'Adolescent, CHU Pontchaillou [Rennes]-Centre Hospitalier Guillaume Régnier [Rennes]-CHS (Centre Hospitalier Spécialisé lutte Maladies Mentales), Laboratoire Psychologie de la Perception (LPP - UMR 8242), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pharmacologie, CHU Pontchaillou [Rennes], CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de neurosciences expérimentales et cliniques (LNEC), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pharmacologie [Rennes], Laboratoire Psychologie de la Perception ( LPP - UMR 8242 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré, Centre d'Investigation Clinique [Rennes] ( CIC ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Poitiers-Centre hospitalier universitaire de Poitiers ( CHU Poitiers ) -Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire de neurosciences expérimentales et cliniques ( LNEC ), and Université de Poitiers-Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: 0301 basic medicine, synchronizer, [SDV]Life Sciences [q-bio], melatonin, Pharmacology, Biology, Antioxidants, Article, sleep-wake rhythm, Melatonin, 03 medical and health sciences, 0302 clinical medicine, Immune system, prevention and treatment, Pharmacokinetics, Prolonged release, Detoxification, medicine, Animals, Humans, Pharmacology (medical), Circadian rhythm, central and peripheral oscillators, Kidney, [ SDV ] Life Sciences [q-bio], Mental Disorders, Brain, General Medicine, adaptation to external and internal environment, 3. Good health, Circadian Rhythm, Psychiatry and Mental health, Biomarker, clinical application, 030104 developmental biology, medicine.anatomical_structure, Neurology, biomarker, Neurology (clinical), 030217 neurology & neurosurgery, hormones, hormone substitutes, and hormone antagonists, biological clocks, medicine.drug
Abstract: International audience; Background: Melatonin synchronizes central but also peripheral oscillators (fetal adrenal gland, pancreas, liver, kidney, heart, lung, fat, gut, etc.), allowing temporal organization of biological functions through circadian rhythms (24-hour cycles) in relation to periodic environmental changes and therefore adaptation of the individual to his/her internal and external environment. Measures of melatonin are considered the best peripheral indices of human circadian timing based on an internal 24-hour clock. Methods: First, the pharmacology of melatonin (biosynthesis and circadian rhythms, pharmacokinetics and mechanisms of action) is described, allowing a better understanding of the short and long term effects of melatonin following its immediate or prolonged release. Then, research related to the physiological effects of melatonin is reviewed. Results: The physiological effects of melatonin are various and include detoxification of free radicals and antioxidant actions, bone formation and protection, reproduction, and cardiovascular, immune or body mass regulation. Also, protective and therapeutic effects of melatonin are reported, especially with regard to brain or gastrointestinal protection, psychiatric disorders, cardiovascular diseases and oncostatic effects. Conclusion: This review highlights the high number and diversity of major melatonin effects and opens important perspectives for measuring melatonin as a biomarker (biomarker of early identification of certain disorders and also biomarker of their follow-up) and using melatonin with clinical preventive and therapeutic applications in newborns, children and adults based on its physiological regulatory effects.
Published: 2017

26. Advances in the Research of Melatonin in Autism Spectrum Disorders: Literature Review and New Perspectives

Author: Nemat Jaafari, Michel Botbol, Olivier Schischmanoff, George M. Anderson, Sylvie Tordjman, Guillaume Bronsard, Sophie Ribardiere, Solenn Kermarrec, Marianne Barbu-Roth, Eric Bellissant, Claire Fougerou, Julie Vernay-Leconte, David Cohen, Imen Najjar, Remi Fagard, Enas Lagdas, Service Psychiatrie de l'Enfant et de l'Adolescent, CHU Pontchaillou [Rennes]-Centre Hospitalier Guillaume Régnier [Rennes]-CHS (Centre Hospitalier Spécialisé lutte Maladies Mentales), Laboratoire Psychologie de la Perception ( LPP - UMR 8242 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Centre National de la Recherche Scientifique ( CNRS ), Centre d'Investigation Clinique [Rennes] ( CIC ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Pharmacologie, CHU Pontchaillou [Rennes], Laboratory of Developmental Neurochemistry, Yale Child Study Center, Department of Laboratory Medicine, Yale School of Medicine, Service de psychiatrie de l'enfant et de l'adolescent, CHU Pitié-Salpêtrière [APHP], CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers ( CHU Poitiers ) -Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Adaptateurs de signalisation en hématologie ( ASIH ), Université Paris 13 ( UP13 ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de biochimie et biologie moléculaire, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne-Université Paris 13 ( UP13 ), Service Hospitalo-Universitaire de Psychiatrie de l'Enfant et de l'Adolescent, Université de Brest ( UBO ), Santé Publique et maladies Chroniques : Qualité de vie Concepts, Usages et Limites, Déterminants ( SPMC ), Aix Marseille Université ( AMU ) -Assistance Publique - Hôpitaux de Marseille ( APHM ), Maison Départementale de l'Adolescent et Centre Médico-Psycho-Pédagogique, Le Corre, Morgane, Laboratoire Psychologie de la Perception (LPP - UMR 8242), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pharmacologie [Rennes], Yale School of Medicine [New Haven, Connecticut] (YSM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Adaptateurs de signalisation en hématologie (ASIH), Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Brest (UBO), Santé Publique et maladies Chroniques : Qualité de vie Concepts, Usages et Limites, Déterminants (SPMC), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Yale University School of Medicine, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: [ SDV.MHEP.PED ] Life Sciences [q-bio]/Human health and pathology/Pediatrics, melatonin, Review, lcsh:Chemistry, Peripheral oscillators, Pineal gland, 0302 clinical medicine, stereotyped behaviors, lcsh:QH301-705.5, Spectroscopy, 0303 health sciences, Social communication, General Medicine, 3. Good health, Computer Science Applications, medicine.anatomical_structure, Communication Disorders, hormones, hormone substitutes, and hormone antagonists, biological clocks, medicine.drug, circadian rhythm, medicine.medical_specialty, endocrine system, autism spectrum disorders, social communication, Catalysis, Inorganic Chemistry, Melatonin, 03 medical and health sciences, Nonverbal communication, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, medicine, Animals, Humans, Circadian rhythm, Physical and Theoretical Chemistry, Psychiatry, Molecular Biology, 030304 developmental biology, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, business.industry, Organic Chemistry, synchrony, medicine.disease, Social relation, lcsh:Biology (General), lcsh:QD1-999, Child Development Disorders, Pervasive, Autism, business, Neuroscience, 030217 neurology & neurosurgery
Abstract: International audience; Abnormalities in melatonin physiology may be involved or closely linked to the pathophysiology and behavioral expression of autistic disorder, given its role in neurodevelopment and reports of sleep-wake rhythm disturbances, decreased nocturnal melatonin production, and beneficial therapeutic effects of melatonin in individuals with autism. In addition, melatonin, as a pineal gland hormone produced from serotonin, is of special interest in autistic disorder given reported alterations in central and peripheral serotonin neurobiology. More specifically, the role of melatonin in the ontogenetic establishment of circadian rhythms and the synchronization of peripheral oscillators opens interesting perspectives to ascertain better the mechanisms underlying the significant relationship found between lower nocturnal melatonin excretion and increased severity of autistic social communication impairments, especially for verbal communication and social imitative play. In this article, first we review the studies on melatonin levels and the treatment studies of melatonin in autistic disorder. Then, we discuss the relationships between melatonin and autistic behavioral impairments with regard to social communication (verbal and non-verbal communication, social interaction), and repetitive behaviors or interests with difficulties adapting to change. In conclusion, we emphasize that randomized clinical trials in autism spectrum disorders are warranted to establish potential therapeutic efficacy of melatonin for social communication impairments and stereotyped behaviors or interests.
Published: 2013

27. Should we keep using Ribavirin to Treat Hepatitis C Recurrence after Liver Transplantation? Results from the CO23 ANRS Cupilt Study

Author: Jean Charles Duclos-Vallée, F. Durand, Valérie Canva, V. Di Martino, Abou Diallo, G.-P. Pageaux, S. Radenne, Claire Fougerou-Leurent, Emilie Rossignol, Aurelie Veislinger, Pauline Houssel-Debry, Rodolphe Anty, H. Danjou, Vincent Leroy, Christophe Duvoux, L. D’Alteroche, C. Silvain, Audrey Coilly, V. de Ledinghen, Camille Besch, Caroline Jezequel, Maryline Debette-Gratien, A. Rohel, François Habersetzer, Nassim Kamar, H. Montialoux, Jérôme Dumortier, Armando Abergel, Christophe Moreno, Fabio Conti, Pascal Lebray, Danielle Botta-Fridlund, P. Perré, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Service d'Hépatologie, Hôpital Henri Mondor, AP-HP, Créteil, France., Hôpital Henri Mondor, Hôpital Paul Brousse, Département d'hépatologie, Hospices Civils de Lyon (HCL), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Services de Maladies de l'Appareil Digestif, Hôpital Claude Huriez, Centre Hospitalier Universitaire de Lille, Lille, France, Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille, CHU Pitié-Salpêtrière [AP-HP], Service d'hépato-gastroentérologie, Hôpital de la Conception, AP-HM, Marseille, Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Laboratoire Inflammation, Tissus épithéliaux et Cytokines (LITEC), Université de Poitiers, Service de Transplantation, Centre Hospitalier Universitaire de Strasbourg, Centre Hospitalier Universitaire de Strasbourg (CHU de Strasbourg ), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Unité de la recherche fondamentale et clinique sur l' hépatite virale, France Recherche Nord & Sud Asdi-VIH Hépatites, Agence Nationale de Recherche sur le Sida, Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: medicine.medical_specialty, Hepatology, business.industry, medicine.medical_treatment, Ribavirin, [SDV]Life Sciences [q-bio], Hepatitis C, 030230 surgery, Liver transplantation, medicine.disease, Gastroenterology, 3. Good health, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, chemistry, Internal medicine, Medicine, 030211 gastroenterology & hepatology, business
Abstract: International audience; EASL International Liver Congress, APR 13-17, 2016, Barcelona, SPAIN
Published: 2016

28. LEDIPASVIR/SOFOSBUVIR IN NS3/4A PROTEASE INHIBITOR-EXPERIENCED SUBJECTS WITH HCV GENOTYPE 1 AND HIV-COINFECTION FINAL RESULTS OF THE ANRS HC31 SOFTRIH STUDY

Author: Elina Teicher, Yazdan Yazdanpanah, Stanislas Pol, J.-M. Molina, Eric Rosenthal, A. Naqvi, M Dupon, E. Billaud, Vincent Leroy, G.-P. Pageaux, P. Perré, Stéphanie Dominguez, Lionel Piroth, S. Metivier, Marc-Antoine Valantin, Hugues Aumaitre, Alain Renault, Patrizia Carrieri, Philippe Morlat, Claire Fougerou-Leurent, I. Amri, R. Garraffo, David Zucman, Stéphane Chevaliez, Isabelle Poizot-Martin, P. de Truchis, Thierry Allegre, Julie Chas, Jacques Reynes, A. Pailhé, Karine Lacombe, Laurent Cotte, Pierre-Marie Girard, Dominique Salmon-Ceron, Eric Bellissant, V. Jeantils, François Bailly, M. Bourlière, François Raffi, Didier Neau, Hôpital l'Archet, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service d'hépatologie médicale [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d'infectiologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service des maladies infectieuses, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service des maladies infectieuses et tropicales [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Services de Maladies Infectieuses et Tropicales [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Hôpital Foch [Suresnes], Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U912 INSERM - Aix Marseille Univ - IRD), Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hépato-gastroentérologie, Assistance Publique - Hôpitaux de Marseille (APHM), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'Investigation Clinique [Rennes] ( CIC ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), CHU Cochin [AP-HP], Centre hospitalier universitaire de Nantes ( CHU Nantes ), Service des maladies infectieuses [CHU Bichat], Hôpital Sainte-Marguerite [CHU - APHM] ( Hôpitaux Sud ), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale ( SESSTIM - U912 INSERM - AMU - IRD ), Institut de Recherche pour le Développement ( IRD ) -Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], and Assistance Publique - Hôpitaux de Marseille ( APHM )
Subjects: 0303 health sciences, [ SDV ] Life Sciences [q-bio], Hepatology, business.industry, [SDV]Life Sciences [q-bio], Virology, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Hcv genotype 1, LEDIPASVIR/SOFOSBUVIR, Medicine, 030211 gastroenterology & hepatology, business, Ns3 4a protease, Hiv co infection, 030304 developmental biology
Abstract: International audience; EASL International Liver Congress, APR 13-17, 2016, Barcelona, SPAIN
Published: 2016

29. Multicentre experience using daclatasvir and sofosbuvir to treat hepatitis C recurrence - The ANRS CUPILT study

Author: Armando Abergel, Christophe Moreno, Danielle Botta-Fridlund, Sylvie Radenne, Maryline Debette-Gratien, Pauline Houssel-Debry, Pascal Lebray, A. Rohel, Claire Francoz, Jean-Charles Duclos-Vallée, P. Perré, François Habersetzer, Nassim Kamar, Christine Silvain, Didier Samuel, H. Danjou, Rodolphe Anty, Vincent Leroy, Emilie Rossignol, Victor de Lédinghen, Louis d’Alteroche, Anne-Marie Roque-Afonso, Camille Besch, Filomena Conti, Christophe Duvoux, Georges-Philippe Pageaux, Valérie Canva, Claire Fougerou-Leurent, Jérôme Dumortier, Vincent Di Martino, Audrey Coilly, Hôpital Paul Brousse, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, Centre hépato-biliaire (CHB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie et traitement des maladies du foie, Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Pôle Recherche Clinique-Santé Publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Service d'hépatologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Hospices Civils de Lyon (HCL)-Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Néphrologie et Transplantation d'organes [CHU Toulouse], Pôle Urologie - Néphrologie - Dialyse - Transplantations - Brûlés - Chirurgie plastique - Explorations fonctionnelles et physiologiques [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), ScaLable Information Discovery and Exploitation [Grenoble] (SLIDE), Laboratoire d'Informatique de Grenoble (LIG ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service d'hépato-gastro-entérologie, Hôpital Huriez-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Pierre et Marie Curie - Paris 6 (UPMC), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), service d'Hépato-gastro-entérologie, Hospices Civiles de Lyon-Hôpital Edouard Heriault, Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Chirurgie Digestive, Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Département Digestif, Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital de l'Archet, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), CHU Pitié-Salpêtrière [AP-HP], Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Interactions Virus-Hôte et Maladies Hépatiques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Virologie, Pathogénèse et traitement de l'hépatite fulminante et du cancer du foie, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hépato-biliaire - CHB [Paul Brousse, Paris], Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse, Hepatinov (DHU), Université Paris-Sud - Paris 11 (UP11)-Centre Hépato-Biliaire Paul Brousse, Centre National de Référence pour la maladie de Wilson (CNR wilson), CNR Wilson, Service de Neurologie, Hôpital Lariboisière, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), ANRS (France REcherche Nord & sud Sida-HIV Hepatites-FRENCH), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Multiorgan Transplantation, CHU Toulouse [Toulouse], Service de gastro-entérologie [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Service de Chirurgie Digestive, Hépato-Bilio-pancréatique et Transplantation Hépatique [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Paul Brousse-Université Paris-Sud - Paris 11 (UP11), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Paul Brousse-Université Paris-Sud - Paris 11 (UP11), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse, Centre hépato-biliaire ( CHB ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AP-HP Hôpital Paul Brousse, Centre d'Investigation Clinique [Rennes] ( CIC ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri-Mondor, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz-Université de Franche-Comté ( UFC ), Hospices Civils de Lyon ( HCL ) -Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon ( HCL ), Institut de médecine moléculaire de Rangueil ( I2MR ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de gastro-entérologie, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], CHRU Tours, ScaLable Information Discovery and Exploitation [Saint Martin d’Hères] ( SLIDE ), Laboratoire d'Informatique de Grenoble ( LIG ), Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut National Polytechnique de Grenoble ( INPG ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut National Polytechnique de Grenoble ( INPG ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Hôpital Huriez-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), APHP, Université Pierre et Marie Curie - Paris 6 ( UPMC ), Hôpital Erasme, Université Libre de Bruxelles [Bruxelles] ( ULB ), Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Assistance Publique - Hôpitaux de Marseille ( APHM ) -Hôpital de la Conception [CHU - APHM] ( LA CONCEPTION ), Centre méditérannéen de médecine moléculaire ( C3M ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ), CHU Nice-Hôpital de l'Archet, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Beaujon, Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques ( RESINFIT ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST ), Université de Limoges ( UNILIM ) -Université de Limoges ( UNILIM ) -CHU Limoges, Service de chirurgie digestive hépato-bilio-pancréatique transplantation hépatique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Human HepCell [AP-HP Hôpital Saint-Antoine], Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AP-HP - Hôpital Saint-Antoine -Paris Biotech santé, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut de Virologie, Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris-Sud - Paris 11 ( UP11 ) -AP-HP Hôpital Paul Brousse, Hepatinov ( DHU ), Université Paris-Sud - Paris 11 ( UP11 ) -Centre Hépato-Biliaire Paul Brousse, Centre National de Référence pour la maladie de Wilson ( CNR wilson ), and Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -CHU Saint-Eloi
Subjects: Compassionate Use Trials, medicine.medical_specialty, drug-drug interactions, Daclatasvir, Sofosbuvir, Hepatitis C virus, medicine.medical_treatment, Hepacivirus, Liver transplantation, medicine.disease_cause, Gastroenterology, Antiviral Agents, virus-infection, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Model for End-Stage Liver Disease, Pegylated interferon, Internal medicine, Ribavirin, medicine, Humans, Prospective Studies, combination, Hepatology, business.industry, association, natural-history, Hepatitis C, interferon, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, medicine.disease, 3. Good health, liver-transplant recipients, hcv infection, [ SDV.SP ] Life Sciences [q-bio]/Pharmaceutical sciences, Treatment Outcome, chemistry, 030220 oncology & carcinogenesis, triple therapy, Immunology, 030211 gastroenterology & hepatology, Drug Therapy, Combination, France, business, medicine.drug
Abstract: International audience; Background & Aims:HCV recurrence remains a major issue in the liver transplant field, as it has a negative impact on both graft and patient survival. The purpose of this study was to investigate the efficacy and safety of treating HCV recurrence with sofosbuvir (SOF) and daclatasvir (DCV) combination therapy. Methods: From October 2013 to March 2015, 559 liver recipients were enrolled in the prospective multicentre France REcherche Nord&Sud Sida-hiv Hepatites (ANRS) Compassionate use of Protease Inhibitors in viral C Liver Transplantation cohort. We selected 137 patients with an HCV recurrence receiving SOF and DCV, whatever the genotype or fibrosis stage. The use of ribavirin and the duration of therapy were at the investigator's discretion. The primary efficacy end point was a sustained virological response (SVR) 12 weeks after the end of treatment. Results: The SVR rate 12 weeks after completing treatment was 96% under the intention-to treat analysis and 99% when excluding non-virological failures. Only two patients experienced a virological failure. The serious adverse event (SAE) rate reached 17.5%. Four patients (3%) stopped their treatment prematurely because of SAEs. Anaemia was the most common AE, with significantly more cases in the ribavirin group (56% vs. 18%; p
Published: 2015

30. Diagnostic contributions of cardiac magnetic resonance imaging in patients presenting with elevated troponin, acute chest pain syndrome and unobstructed coronary arteries

Author: Dominique Boulmier, Pierre-Axel Lentz, Marc Bedossa, Hervé Le Breton, Guillaume Leurent, B. Langella, A. Larralde, Claire Fougerou, Service de cardiologie et maladies vasculaires [Rennes] = Cardiac, Thoracic, and Vascular Surgery [Rennes], CHU Pontchaillou [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC-IT Rennes, Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de radiologie et imagerie médicale [Rennes] = Radiology [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Myocardite, MESH: Chi-Square Distribution, Cardiac magnetic resonance, Myocardial Infarction, Contrast Media, MESH: Takotsubo Cardiomyopathy, 030204 cardiovascular system & hematology, Coronary Angiography, Chest pain, Coronary artery disease, 0302 clinical medicine, MESH: Up-Regulation, MESH: Coronary Vessels, MESH: Syndrome, Prospective Studies, 030212 general & internal medicine, Myocardial infarction, MESH: Myocardial Perfusion Imaging, Ejection fraction, biology, medicine.diagnostic_test, MESH: Chest Pain, Syndrome de takotsubo, Myocardial Perfusion Imaging, MESH: Magnetic Resonance Imaging, Cine, Syndrome, General Medicine, Syndrome coronaire aigu, Coronary Vessels, MESH: Predictive Value of Tests, Troponin, Up-Regulation, 3. Good health, MESH: Myocardial Infarction, Myocarditis, MESH: Young Adult, Acute Disease, cardiovascular system, Cardiology, MESH: Acute Disease, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Female, Acute coronary syndrome, France, Radiology, medicine.symptom, Takotsubo syndrome, Cardiology and Cardiovascular Medicine, Adult, Chest Pain, medicine.medical_specialty, Magnetic Resonance Imaging, Cine, Infarctus du myocarde, MESH: Meglumine, Young Adult, 03 medical and health sciences, Meglumine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, MESH: Myocarditis, Predictive Value of Tests, Takotsubo Cardiomyopathy, Cardiac magnetic resonance imaging, MESH: Contrast Media, Internal medicine, Organometallic Compounds, medicine, Humans, MESH: Humans, Chi-Square Distribution, business.industry, MESH: Biological Markers, MESH: Adult, MESH: Organometallic Compounds, medicine.disease, MESH: Male, MESH: Prospective Studies, MESH: Coronary Angiography, MESH: France, IRM cardiaque, biology.protein, MESH: Troponin, Myocardial infarction diagnosis, business, human activities, MESH: Female, Biomarkers
Abstract: International audience; AIMS: Myocardial infarction with unobstructed coronary artery disease represents a serious diagnostic challenge. The role of cardiac magnetic resonance in the management of cardiomyopathies is increasing. We examined the diagnostic contributions of cardiac magnetic resonance in patients presenting with acute chest pain syndrome, elevated serum cardiac troponin concentrations and no significant coronary artery stenoses. METHODS: Over a 3-year period, 107 consecutive patients (mean age 43.5 years; 62% men) presented to our institution with acute onset of chest pain, elevated serum troponin concentration and unobstructed coronary arteries, and underwent 3-tesla cardiac magnetic resonance at a mean delay of 6.9 days. A diagnosis was made based on: wall motion abnormalities and pericardial effusion on cine mode; myocardial oedema on T2-weighted imaging; abnormalities on first-pass perfusion imaging; and late gadolinium enhancement on T1-weighted imaging. RESULTS: Cardiac magnetic resonance was normal in 10.3% of patients and contributed a diagnosis in 89.7%, including myocarditis in 59.9%, stress cardiomyopathy (takotsubo syndrome) in 14% and myocardial infarction in 15.8%. Patients with normal cardiac magnetic resonance had a significantly lower mean peak troponin concentration (2.6ng/mL) than patients with diagnostic cardiac magnetic resonance (9.7ng/mL; P=0.01). CONCLUSION: Cardiac magnetic resonance contributed a diagnosis in nearly 90% of patients presenting with acute chest pain, elevated serum troponin and unobstructed coronary arteries.
Published: 2011
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31. O109 : Treatment of severe HCV-recurrence after liver transplantation using sofosbuvir-based regimens: The ANRS CO23 CUPILT study

Author: G.-P. Pageaux, Jean Charles Duclos-Vallée, F. Durand, L. D’Alteroche, Valérie Canva, H. Danjou, Audrey Coilly, Vincent Leroy, Danielle Botta-Fridlund, Claire Fougerou-Leurent, Pauline Houssel-Debry, Abou Diallo, Fabio Conti, Nassim Kamar, V. Di Martino, S. Radenne, Christophe Duvoux, A. Rohel, V. de Ledinghen, Jérôme Dumortier, Département d'hépatologie, Hospices Civils de Lyon (HCL), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Néphrologie et Transplantation d'organes [CHU Toulouse], Pôle Urologie - Néphrologie - Dialyse - Transplantations - Brûlés - Chirurgie plastique - Explorations fonctionnelles et physiologiques [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Multiorgan Transplantation, and CHU Toulouse [Toulouse]
Subjects: medicine.medical_specialty, Hepatology, Sofosbuvir, business.industry, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Hcv recurrence, Liver transplantation, Gastroenterology, 3. Good health, Internal medicine, medicine, business, ComputingMilieux_MISCELLANEOUS, medicine.drug
Abstract: International audience; no abstract
Published: 2015

32. Ledipasvir/sofosbuvir chez les patients co-infectés par le VIH et un VHC de génotype 1 prétraités par un inhibiteur de la protéase NS3/A4 du VHC (étude ANRS HC31 SOFTRIH)

Author: Groupe Anrs Hc Softrih, Eric Bellissant, Eric Rosenthal, Claire Fougerou-Leurent, Hugues Aumaitre, Alain Renault, Karine Lacombe, A. Naqvi, E Teicher, François Bailly, Jean-Michel Molina, M. Bourlière, Philippe Morlat, Hôpital l'Archet, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hépato-gastroentérologie, Assistance Publique - Hôpitaux de Marseille (APHM), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Jonchère, Laurent
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], Gastroenterology, Internal Medicine, 3. Good health
Abstract: National audience; Introduction L’association fixe d’antiviraux directs ledipasvir/sofosbuvir (LDV/SOF), disponible sous la forme d’un comprimé unique, n’a pas été étudiée spécifiquement chez les patients chroniquement infectés par un VHC de génotype 1 (G1), co-infectés par le VIH et en échec d’un traitement préalable incluant un inhibiteur de la protéase (IP) NS3/A4 du VHC. Nous avons évalué l’efficacité et la tolérance de cette combinaison dans cette population de patients, historiquement considérés comme très difficiles à traiter (étude ANRS HC31 SOFTRIH). Patients et méthodes Les patients infectés de manière chronique par un VHC G1, co-infectés par le VIH et sous traitement antirétroviral stable (ARV), en échec d’un traitement anti-VHC antérieur par interféron pégylé/ribavirine/IP NS3/A4 ou ayant interrompu précocement ce traitement pour intolérance, ont été inclus dans cette étude prospective. Tous les patients ont reçu la combinaison fixe LDV/SOF (90 mg/400 mg), une fois par jour pendant 12 semaines ou 24 semaines en cas cirrhose hépatique. Les patients pouvaient également recevoir les ARVs suivants : tenofovir, emtricitabine,lamivudine, raltegravir, efavirenz, rilpivirine, enfuvirtide. Les critères de jugement d’efficacité étaient l’obtention d’une réponse virologique soutenue, définie par un ARN VHC indétectable 4 semaines (RVS4) ou 12 semaines (RVS12, critère principal) après l’arrêt du traitement. La survenue d’effets indésirables (EIs) et les paramètres biologiques standards incluant la numération des lymphocytes CD4 et l’ARN VIH ont été étudiés. Résultats Soixante-huit patients avec un G1a (82,5 %), un G1b (13 %) ou un autre G1 (4,5 %) ont été inclus : hommes 79 % ; âge moyen 52 ans ; médiane de l’ARN VHC (6,2 Log UI/mL) et des lymphocytes CD4 (629/mm3) à l’inclusion ; cirrhose compensée (40 %). Soixante-cinq patients étaient évaluables pour les critères virologiques. Soixante-deux patients (95,4 %) ont obtenu une RVS4 (prélèvement sanguin non disponible chez 1 patient, ARN VHC détectable inférieur au seuil de quantification chez 2 patients). Tous les patients (100 %) ont obtenu une RVS12. Deux patients ont présenté un rebond virologique VIH confirmé. Aucun patient n’a interrompu précocement le traitement de l’étude pour intolérance. Les EIs constatés chez plus de 10 % des patients étaient les suivants : fatigue (19,1 %), pression artérielle élevée (14,7 %), céphalées (11,8 %). Conclusion Si les études ERADICATE [1] et ION-4 [2] ont récemment montré une efficacité et une tolérance très bonnes de l’association LDV/SOF chez les patients co-infectés par le VIH, notre étude apporte des résultats supplémentaires chez les patients historiquement considérés comme très difficiles à traiter, incluant ceux présentant une cirrhose hépatique
Published: 2015

33. Sofosbuvir-Based-Regimen for HCV Recurrence after Combined Liver-Kidney Transplantation : Results from the ANRS CO23 Cupilt Study

Author: V. Di Martino, P. Perré, A. Tran, François Habersetzer, Danielle Botta-Fridlund, C. Silvain, L. D’Alteroche, G.-P. Pageaux, Claire Fougerou-Leurent, H. Montialoux, Vincent Leroy, Jérôme Dumortier, Audrey Coilly, Christophe Duvoux, V. de Ledinghen, Pauline Houssel-Debry, Camille Besch, Maryline Debette-Gratien, S. Radenne, Nassim Kamar, Jean-Charles Duclos Vallee, Valérie Canva, Armando Abergel, Christophe Moreno, Sébastien Dharancy, Fabio Conti, Claire Francoz, and A. Rohel
Subjects: medicine.medical_specialty, Liver kidney transplantation, Hepatology, Sofosbuvir, business.industry, Hcv recurrence, Gastroenterology, 03 medical and health sciences, Regimen, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, medicine, 030211 gastroenterology & hepatology, business, medicine.drug
Published: 2016

34. Day and nighttime excretion of 6-sulphatoxymelatonin in adolescents and young adults with autistic disorder

Author: Sylvie Tordjman, George M. Anderson, Eric Bellissant, David Cohen, Solenn Kermarrec, Françoise Camus, Henriette Charbuy, Claire Fougerou, Yvan Touitou, Rozenn Graignic, and Michel Botbol
Subjects: Male, medicine.medical_specialty, Adolescent, Endocrinology, Diabetes and Metabolism, Nocturnal, Neuropsychological Tests, Urine, Spearman's rank correlation coefficient, Melatonin, Excretion, Young Adult, Endocrinology, Internal medicine, medicine, Humans, Circadian rhythm, Young adult, Autistic Disorder, Biological Psychiatry, Endocrine and Autonomic Systems, Case-control study, medicine.disease, Circadian Rhythm, Psychiatry and Mental health, Case-Control Studies, Autism, Female, Psychology, medicine.drug
Abstract: Several reports indicate that nocturnal production of melatonin is reduced in autism. Our objective was to examine whether melatonin production is decreased during the whole 24-h cycle, whether the melatonin circadian rhythm is inverted, and whether the reduction in melatonin production is related to the severity of autistic behavioral impairments.Day and nighttime urinary excretion of 6-sulphatoxymelatonin (6-SM) was examined during a 24-h period in post-pubertal individuals with autism (N=43) and typically developing controls (N=26) matched for age, sex and pubertal stage.Low 6-SM excretion (mean ± SEM) was observed in autism, both at daytime (0.16 ± 0.03 vs. 0.36 ± 0.05 μg/h, p0.01), nighttime (0.52 ± 0.07 vs. 1.14 ± 0.23 μg/h, p0.05), and during 24h (8.26 ± 1.27 vs. 18.00 ± 3.43 μg/24-h collection, p0.001). Intra-individual nighttime-daytime differences (delta values) in 6-SM excretion were smaller in individuals with autism than in controls (0.36 ± 0.07 vs. 0.79 ± 0.23 μg/h, p0.05). Nocturnal excretion of 6-SM was negatively correlated with autism severity in the overall level of verbal language (Spearman ρ=-0.30, p0.05), imitative social play (Spearman ρ=-0.42, p0.05), and repetitive use of objects (Spearman ρ=-0.36, p0.05).A deficit in melatonin production is present both at daytime and at nighttime in individuals with autism, particularly in the most severely affected individuals. These results highlight interest in potential therapeutic uses of melatonin in autistic disorder, especially in individuals with severe autistic impairment and/or low urinary 6-SM excretion.
Published: 2011

35. Gluco- and mineralocorticoid biological effects of a 7-day treatment with low doses of hydrocortisone and fludrocortisone in septic shock

Author: Eric Bellissant, Djillali Annane, Bruno Laviolle, and Claire Fougerou
Subjects: Blood Glucose, medicine.medical_specialty, Hydrocortisone, medicine.drug_class, Fludrocortisone, Anti-Inflammatory Agents, Urine, Critical Care and Intensive Care Medicine, Leukocyte Count, Body Water, Double-Blind Method, Internal medicine, medicine, Humans, Dose-Response Relationship, Drug, business.industry, Septic shock, Osmolar Concentration, Sodium, medicine.disease, Shock, Septic, Eosinophils, Dose–response relationship, Endocrinology, Cholesterol, Mineralocorticoid, Shock (circulatory), Potassium, Drug Therapy, Combination, medicine.symptom, business, Glucocorticoid, medicine.drug, Hormone
Abstract: The benefits of low-dose steroids in septic shock remain controversial. We investigated if these low doses were able to induce their expected hormonal effects by analyzing the biological modifications observed during the study, which first demonstrated the survival benefit of low-dose steroids.This was a multicenter, placebo-controlled, randomized, double-blind study in which 299 septic shock patients received a 7-day treatment with a combination of hydrocortisone (50 mg intravenously four times daily) and fludrocortisone (50 μg orally once daily) or matching placebos. Gluco- and mineralocorticoid biological effects observed during the 7 days of treatment were compared between groups.Steroids significantly decreased eosinophil counts from day 2 to day 7. Steroids significantly increased plasma glucose from day 2 (compared with placebos: +0.8 mmol/l) to day 7 (+1.8 mmol/l) and cholesterol from day 3 (+0.54 mmol/l) to day 7 (+0.39 mmol/l). Steroids significantly increased plasma sodium from day 3 (+2 mmol/l) to day 7 (+5 mmol/l) and significantly decreased plasma potassium on day 7 (-0.2 mmol/l). Steroids significantly decreased urinary sodium/potassium ratio from day 2 (-47 %) to day 7 (-57 %) and sodium fractional excretion from day 3 (-25 %) to day 7 (-66 %). Steroids significantly increased urine output on day 4 and 5 and osmolar clearance from day 4 to day 7, and decreased free-water clearance from day 4 to day 7, this effect being significant on day 4 and 6.In septic shock, low-dose steroids induced both gluco- and mineralocorticoid biological effects and seemed to improve renal function. Most of these effects appeared after 2-3 days of treatment and lasted at least until the end of treatment.
Published: 2011

36. Door-to-balloon delays before primary angioplasty in the Regional Acute Myocardial Infarction Registry of Brittany. An analysis of the Observatoire Régional Breton sur l'Infarctus du myocarde (ORBI)

Author: Claire Fougerou, Christian Hamon, Hubert Courcoux, Isabelle Coudert, Josiane Treuil, Dominique Boulmier, Marc Bedossa, Benoit Moquet, Jean-Philippe Hacot, Pierre-Yves Pennec, Emmanuelle Filippi, Guillaume Leurent, Hervé Le Breton, Renaud Gervais, Philippe Druelles, Gilles Rouault, Antoine Rialan, B. Boulanger, Service de cardiologie et maladies vasculaires [Rennes] = Cardiac, Thoracic, and Vascular Surgery [Rennes], CHU Pontchaillou [Rennes], CIC-IT Rennes, Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de cardiologie [Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de cardiologie [Vannes], Centre hospitalier de Vannes, Service de Cardiologie [Saint Brieuc], CH Saint Brieuc, Service des urgences [Rennes] = Emergency [Rennes], Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and CHU de Saint-Brieuc
Subjects: Male, MESH: Process Assessment (Health Care), Time Factors, MESH: Registries, Infarctus aigu du myocarde, medicine.medical_treatment, Myocardial Infarction, MESH: Logistic Models, 030204 cardiovascular system & hematology, MESH: Risk Assessment, Health Services Accessibility, 0302 clinical medicine, Patient Admission, MESH: Practice Guidelines as Topic, [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, Risk Factors, MESH: Risk Factors, Emergency medical services, Odds Ratio, 030212 general & internal medicine, Myocardial infarction, Prospective Studies, Registries, Angioplasty, Balloon, Coronary, MESH: Aged, MESH: Health Services Accessibility, MESH: Middle Aged, Angioplastie primaire, Process Assessment, Health Care, General Medicine, Middle Aged, 3. Good health, MESH: Angioplasty, Balloon, Coronary, MESH: Myocardial Infarction, Practice Guidelines as Topic, MESH: Guideline Adherence, MESH: Emergency Medical Services, Female, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Transports des patients, France, Guideline Adherence, Service d’aide médicalisée d’urgence, Cardiology and Cardiovascular Medicine, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Patient Transfer, MESH: After-Hours Care, medicine.medical_specialty, Primary angioplasty, Acute myocardial infarction, Risk Assessment, MESH: Patient Transfer, Transportation of patients, 03 medical and health sciences, First responder, After-Hours Care, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Premier contact, Angioplasty, medicine, Humans, Aged, MESH: Humans, Interventional cardiology, business.industry, MESH: Patient Admission, MESH: Time Factors, Emergency department, medicine.disease, MESH: Male, MESH: Odds Ratio, MESH: Prospective Studies, Surgery, MESH: France, Logistic Models, Emergency medicine, Door-to-balloon, First aid, business, MESH: Female
Abstract: SummaryBackgroundMinimizing delays to coronary reperfusion is critical in the management of acute myocardial infarction (AMI).AimsTo determine delays in in-hospital management and factors associated with delays of over 45min.MethodsWe analysed data from the Observatoire Régional Breton sur l’Infarctus, a registry of AMI patients admitted within 24h of symptom onset (July 2007 to December 2008) to an interventional cardiology centre in Brittany. Prehospital delay was defined as time between first responder arrival at the patient and patient arrival at an interventional cardiovascular centre. In-hospital delay was defined as time between admission to the interventional cardiovascular centre and first balloon inflation. Patients were grouped according to duration of in-hospital delay (>45 vs ≤45min). Predictors of short in-hospital delay (≤45min) were examined by logistic regression analysis.ResultsThe analysis included 560 patients (mean age 60.7±13 years; 443 men). Median delay between symptom onset and call for medical assistance was 50min (mean 115±180). Two-thirds (n=371) of patients were admitted to hospital during working hours (08:00–20:00h); 383 (68%) patients were managed by emergency medical services before admission. In-hospital delay was less than or equal to 45min for 296 (53%) patients. The mean overall (pre- and in-hospital) delay was 140 (median 109) min. Direct admission to a catheterization laboratory and admission during working hours were independently correlated with short in-hospital delay (odds ratios 20.8 [p
Published: 2009

37. Cardiac MRI studies of transient left ventricular apical ballooning syndrome (takotsubo cardiomyopathy): a systematic review

Author: Hervé Le Breton, Romain Ollivier, Dominique Boulmier, Marc Bedossa, Guillaume Leurent, B. Langella, A. Larralde, Claire Fougerou, Service de cardiologie et maladies vasculaires [Rennes] = Cardiac, Thoracic, and Vascular Surgery [Rennes], CHU Pontchaillou [Rennes], CIC-IT Rennes, Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de radiologie et imagerie médicale [Rennes] = Radiology [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: medicine.medical_specialty, Heart disease, Cardiomyopathy, 030204 cardiovascular system & hematology, Mri studies, MESH: Takotsubo Cardiomyopathy, 030218 nuclear medicine & medical imaging, MESH: Magnetic Resonance Imaging, Ventricular Dysfunction, Left, 03 medical and health sciences, 0302 clinical medicine, Text mining, [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, MESH: Ventricular Dysfunction, Left, medicine, Humans, Thrombus, Cardiac MRI, Left ventricular dysfunction, Left Ventricular Apical Ballooning Syndrome, Ejection fraction, MESH: Humans, medicine.diagnostic_test, business.industry, Magnetic resonance imaging, medicine.disease, Magnetic Resonance Imaging, 3. Good health, Transient left ventricular apical ballooning syndrome, Cardiology, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Takotsubo cardiomyopathy, Cardiology and Cardiovascular Medicine, business, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing
Abstract: International audience; BACKGROUND: Since its first description in 1991, many cases of transient left ventricular apical ballooning syndrome (TLVABS) have been described, but the use of cardiac MRI in this condition is much more recent. METHODS AND RESULTS: We performed a systematic review of the present literature in the MEDLINE and EMBASE databases for relevant case series of TLVABS (>or=5 reported original cases, MRI analysis in the acute phase) and summarized the main results in a narrative synthesis. Only 8 studies met the eligible criteria, counting 176 patients (women: 95%; age: 68, stress trigger: 80%). MRI assessed an improvement of mean left ventricular ejection fraction from 39 (in the acute phase) to 64% (in the recovery phase). A right ventricular dysfunction was reported in 38%, a myocardial oedema in 81% and an apical thrombus in 5%. CONCLUSIONS: Although cardiac MRI is a very useful and inescapable tool in the management of TLVABS, there is no large published study concerning this topic. A systematic and multicentric register of TLVABS studied by cardiac MRI is necessary.
Published: 2009

38. Argument for a Doppler echocardiography during exercise in assessing asymptomatic patients with severe aortic stenosis

Author: M. Laurent, Alain Le Helloco, Philippe Mabo, Christian de Place, Erwan Donal, Céline Chabanne, Guillaume Leurent, Renaud Gervais, Jean-Claude Daubert, Claire Fougerou, Service de cardiologie et maladies vasculaires [Rennes] = Cardiac, Thoracic, and Vascular Surgery [Rennes], CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Aortic valve, Cardiac output, 030204 cardiovascular system & hematology, Doppler echocardiography, Aortic valve stenosis, Severity of Illness Index, 0302 clinical medicine, [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, Heart Rate, Reference Values, Prospective Studies, 030212 general & internal medicine, Cardiac Output, Prospective cohort study, medicine.diagnostic_test, General Medicine, Middle Aged, Echocardiography, Doppler, Exercise stress test, medicine.anatomical_structure, Echocardiography, Cardiology, Regression Analysis, Female, [SDV.IB]Life Sciences [q-bio]/Bioengineering, medicine.symptom, Cardiology and Cardiovascular Medicine, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Echocardiography, Stress, medicine.medical_specialty, Risk Assessment, Sensitivity and Specificity, Asymptomatic, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, Adverse effect, Aged, Probability, business.industry, Hemodynamics, Reproducibility of Results, Stroke Volume, medicine.disease, Stenosis, business
Abstract: International audience; Aims : Exercise stress testing (EST) is recommended by guidelines to risk-stratify patients with asymptomatic valvular aortic stenosis (AS), though the role of quantitative exercise-Doppler echocardiography has rarely been studied. This prospective study sought to correlate standard EST results with the haemodynamic measurements made during exercise by Doppler echocardiography. Methods and results : We performed rest and semi-supine exercise Doppler echocardiography in 44 consecutive patients (mean age = 68 ± 12 years) with aortic valve areas ≤0.6 cm2/m2. The effective aortic valve area (EOA), cardiac output (CO), maximal transvalvular velocity, and pulmonary pressure were monitored over the test. No serious adverse event was observed. EST was positive in 26 (Group 1) and negative in 18 (Group 2) patients. Baseline echocardiographic measurements were similar (EOA 0.77 ± 0.15 vs. 0.78 ± 0.14 cm2; CO 5.5 ± 1.6 vs. 5.9 ± 2 L/min) in both groups. Exercise-induced changes in CO (+2.9 ± 2 vs. +4.3 ± 1.8 L/min, P = 0.04) and EOA (−0.04 ± 0.18 vs. +0.15 ± 0.24 cm2, P = 0.015) were significantly greater in Group 2. A correlation between changes in EOA and changes in CO during exercise was observed, but significantly higher in Group 2 (P = 0.04). Conclusion : In the presence of severe asymptomatic AS, exercise Doppler echocardiography, assessing the mechanisms behind a positive EST, appears very promising but further studies with prognosis assessment remain necessary.
Published: 2009

39. Argument for a Doppler echocardiography during exercise in assessing asymptomatic patients with severe aortic stenosis.

Author: Guillaume Leurent, Erwan Donal, Christian de Place, Céline Chabanne, Renaud Gervais, Claire Fougerou, Alain le Helloco, Jean-Claude Daubert, Philippe Mabo, and Marcel Laurent
Abstract: Aims Exercise stress testing (EST) is recommended by guidelines to risk-stratify patients with asymptomatic valvular aortic stenosis (AS), though the role of quantitative exercise-Doppler echocardiography has rarely been studied. This prospective study sought to correlate standard EST results with the haemodynamic measurements made during exercise by Doppler echocardiography. Methods and results We performed rest and semi-supine exercise Doppler echocardiography in 44 consecutive patients (mean age = 68 ± 12 years) with aortic valve areas ≤0.6 cm2/m2. The effective aortic valve area (EOA), cardiac output (CO), maximal transvalvular velocity, and pulmonary pressure were monitored over the test. No serious adverse event was observed. EST was positive in 26 (Group 1) and negative in 18 (Group 2) patients. Baseline echocardiographic measurements were similar (EOA 0.77 ± 0.15 vs. 0.78 ± 0.14 cm2; CO 5.5 ± 1.6 vs. 5.9 ± 2 L/min) in both groups. Exercise-induced changes in CO (+2.9 ± 2 vs. +4.3 ± 1.8 L/min, P = 0.04) and EOA (−0.04 ± 0.18 vs. +0.15 ± 0.24 cm2, P = 0.015) were significantly greater in Group 2. A correlation between changes in EOA and changes in CO during exercise was observed, but significantly higher in Group 2 (P = 0.04). Conclusion In the presence of severe asymptomatic AS, exercise Doppler echocardiography, assessing the mechanisms behind a positive EST, appears very promising but further studies with prognosis assessment remain necessary. [ABSTRACT FROM AUTHOR]
Published: 2009
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40. Extracorporeal Membrane Oxygenation for Respiratory Failure Related to COVID-19: A Nationwide Cohort Study

Author: Nicolas, Nesseler, Guillaume, Fadel, Alexandre, Mansour, Marylou, Para, Pierre-Emmanuel, Falcoz, Nicolas, Mongardon, Alizée, Porto, Astrid, Bertier, Bruno, Levy, Cyril, Cadoz, Pierre-Grégoire, Guinot, Olivier, Fouquet, Jean-Luc, Fellahi, Alexandre, Ouattara, Julien, Guihaire, Vito-Giovanni, Ruggieri, Philippe, Gaudard, François, Labaste, Thomas, Clavier, Kais, Brini, Nicolas, Allou, Corentin, Lacroix, Juliette, Chommeloux, Guillaume, Lebreton, Michael A, Matthay, Sophie, Provenchere, Erwan, Flécher, André, Vincentelli, James T, Ross, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-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 Pontchaillou [Rennes], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Nanomédecine Régénérative (NanoRegMed), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), CHU Strasbourg, Nouvel Hôpital Civil de Strasbourg, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor, Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital Bicêtre, 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), Service de Cardiologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-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 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 Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], Hypertension pulmonaire : physiopathologie et innovation thérapeutique (HPPIT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hôpital Marie-Lannelongue, Groupe Hospitalier Paris Saint-Joseph (hpsj), Centre Hospitalier Universitaire de Reims (CHU Reims), Université de Reims Champagne-Ardenne (URCA), 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), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Franco-czech Laboratory for clinical research on obesity, Charles University [Prague] (CU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Rouen, Normandie Université (NU), Institut Mutualiste de Montsouris (IMM), Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion], Centre hospitalier universitaire de Poitiers (CHU Poitiers), University of California [San Francisco] (UC San Francisco), University of California (UC), Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Lille, ECMOSARS Investigators: Marc Pierrot, Sidney Chocron, Guillaume Flicoteaux, Philippe Mauriat, Hadrien Roze, Olivier Huet, Marc-Olivier Fischer, Claire Alessandri, Raphel Bellaïche, Ophélie Constant, Quentin de Roux, André Ly, Arnaud Meffert, Jean-Claude Merle, Lucile Picard, Elena Skripkina, Thierry Folliguet, Antonio Fiore, Nicolas d'Ostrevy, Marie-Catherine Morgan, Maxime Nguyen, Lucie Gaide-Chevronnay, Nicolas Terzi, Gwenhaël Colin, Olivier Fabre, Arash Astaneh, Justin Issard, Elie Fadel, Dominique Fabre, Antoine Girault, Iolande Ion, Jean Baptiste Menager, Delphine Mitilian, Olaf Mercier, François Stephan, Jacques Thes, Jerôme Jouan, Thibault Duburcq, Valentin Loobuyck, Sabrina Manganiello, Mouhammed Moussa, Agnes Mugnier, Natacha Rousse, Olivier Desebbe, Roland Henaine, Matteo Pozzi, Jean-Christophe Richard, Zakaria Riad, Christophe Guervilly, Sami Hraiech, Laurent Papazian, Matthias Castanier, Charles Chanavaz, Sebastien Gette, Guillaume Louis, Erick Portocarrero, Nicolas Bischoff, Antoine Kimmoun, Mathieu Mattei, Pierre Perez, Alexandre Bourdiol, Yannick Hourmant, Pierre-Joachim Mahé, Bertrand Rozec, Mickaël Vourc'h, Stéphane Aubert, Florian Bazalgette, Claire Roger, Pierre Jaquet, Brice Lortat-Jacob, Pierre Mordant, Patrick Nataf, Juliette Patrier, Morgan Roué, Romain Sonneville, Alexy Tran-Dinh, Paul-Henri Wicky, Charles Al Zreibi, Bernard Cholley, Yannis Guyonvarch, Sophie Hamada, Claudio Barbanti, Anatole Harrois, Jordi Matiello, Thomas Kerforne, Nicolas Brechot, Alain Combes, Jean Michel Constantin, Cosimo D'Alessandro, Pierre Demondion, Alexandre Demoule, Martin Dres, Muriel Fartoukh, Guillaume Hekimian, Charles Juvin, Pascal Leprince, David Levy, Charles Edouard Luyt, Marc Pineton de Chambrun, Matthieu Schmidt, Thibaut Schoell, Pierre Fillâtre, Nicolas Massart, Roxane Nicolas, Maud Jonas, Charles Vidal, Salvatore Muccio, Dario Di Perna, Bruno Mourvillier, Amedeo Anselmi, Karl Bounader, Maxime Esvan, Claire Fougerou-Leurent, Yoann Launey, Thomas Lebouvier, Alessandro Parasido, Florian Reizine, Philippe Seguin, Emmanuel Besnier, Dorothée Carpentier, Anne Olland, Fanny Bounes, Vincent Minville, Antoine Guillon, Yannick Fedun, James T Ross, Jonchère, Laurent, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN], Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), CHU Toulouse [Toulouse], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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 Universitaire de La Réunion (CHU La Réunion), University of California [San Francisco] (UCSF), University of California, 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), 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)-Université Claude Bernard Lyon 1 (UCBL)
Subjects: Cohort Studies, Male, [SDV] Life Sciences [q-bio], Anesthesiology and Pain Medicine, Extracorporeal Membrane Oxygenation, [SDV]Life Sciences [q-bio], COVID-19, Humans, Respiratory Insufficiency, Pandemics, Retrospective Studies
Abstract: Background Despite expanding use, knowledge on extracorporeal membrane oxygenation support during the COVID-19 pandemic remains limited. The objective was to report characteristics, management, and outcomes of patients receiving extracorporeal membrane oxygenation with a diagnosis of COVID-19 in France and to identify pre-extracorporeal membrane oxygenation factors associated with in-hospital mortality. A hypothesis of similar mortality rates and risk factors for COVID-19 and non–COVID-19 patients on venovenous extracorporeal membrane oxygenation was made. Methods The Extracorporeal Membrane Oxygenation for Respiratory Failure and/or Heart failure related to Severe Acute Respiratory Syndrome-Coronavirus 2 (ECMOSARS) registry included COVID-19 patients supported by extracorporeal membrane oxygenation in France. This study analyzed patients included in this registry up to October 25, 2020, and supported by venovenous extracorporeal membrane oxygenation for respiratory failure with a minimum follow-up of 28 days after cannulation. The primary outcome was in-hospital mortality. Risk factors for in-hospital mortality were analyzed. Results Among 494 extracorporeal membrane oxygenation patients included in the registry, 429 were initially supported by venovenous extracorporeal membrane oxygenation and followed for at least 28 days. The median (interquartile range) age was 54 yr (46 to 60 yr), and 338 of 429 (79%) were men. Management before extracorporeal membrane oxygenation cannulation included prone positioning for 411 of 429 (96%), neuromuscular blockage for 419 of 427 (98%), and NO for 161 of 401 (40%). A total of 192 of 429 (45%) patients were cannulated by a mobile extracorporeal membrane oxygenation unit. In-hospital mortality was 219 of 429 (51%), with a median follow-up of 49 days (33 to 70 days). Among pre-extracorporeal membrane oxygenation modifiable exposure variables, neuromuscular blockage use (hazard ratio, 0.286; 95% CI, 0.101 to 0.81) and duration of ventilation (more than 7 days compared to less than 2 days; hazard ratio, 1.74; 95% CI, 1.07 to 2.83) were independently associated with in-hospital mortality. Both age (per 10-yr increase; hazard ratio, 1.27; 95% CI, 1.07 to 1.50) and total bilirubin at cannulation (6.0 mg/dl or more compared to less than 1.2 mg/dl; hazard ratio, 2.65; 95% CI, 1.09 to 6.5) were confounders significantly associated with in-hospital mortality. Conclusions In-hospital mortality was higher than recently reported, but nearly half of the patients survived. A high proportion of patients were cannulated by a mobile extracorporeal membrane oxygenation unit. Several factors associated with mortality were identified. Venovenous extracorporeal membrane oxygenation support should be considered early within the first week of mechanical ventilation initiation. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New
Published: 2022

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