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1. The Clinical Frailty Scale for mortality prediction of old acutely admitted intensive care patients: a meta-analysis of individual patient-level data

Author: Raphael Romano Bruno, Bernhard Wernly, Sean M. Bagshaw, Mark van den Boogaard, Jai N. Darvall, Lina De Geer, Pablo Ruiz de Gopegui Miguelena, Daren K. Heyland, David Hewitt, Aluko A. Hope, Emilie Langlais, Pascale Le Maguet, Carmel L. Montgomery, Dimitrios Papageorgiou, Philippe Seguin, Wytske W. Geense, J. Alberto Silva-Obregón, Georg Wolff, Amin Polzin, Lisa Dannenberg, Malte Kelm, Hans Flaatten, Michael Beil, Marcus Franz, Sigal Sviri, Susannah Leaver, Bertrand Guidet, Ariane Boumendil, Christian Jung, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Université de Rennes (UR), CHU Pontchaillou [Rennes], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Open Access funding enabled and organized by Projekt DEAL. This work was supported by the Forschungskommission of the Medical Faculty of the Heinrich-Heine-University Düsseldorf, No. 2018-32 to GW and No. 2020-21 to RRB for a Clinician Scientist Track.
Subjects: All institutes and research themes of the Radboud University Medical Center, Elderly, Frailty, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Individual patient-level data meta-analysis, Systematic review, Intensive care medicine, Outcome prediction, Critical Care and Intensive Care Medicine, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18]
Abstract: Background This large-scale analysis pools individual data about the Clinical Frailty Scale (CFS) to predict outcome in the intensive care unit (ICU). Methods A systematic search identified all clinical trials that used the CFS in the ICU (PubMed searched until 24th June 2020). All patients who were electively admitted were excluded. The primary outcome was ICU mortality. Regression models were estimated on the complete data set, and for missing data, multiple imputations were utilised. Cox models were adjusted for age, sex, and illness acuity score (SOFA, SAPS II or APACHE II). Results 12 studies from 30 countries with anonymised individualised patient data were included (n = 23,989 patients). In the univariate analysis for all patients, being frail (CFS ≥ 5) was associated with an increased risk of ICU mortality, but not after adjustment. In older patients (≥ 65 years) there was an independent association with ICU mortality both in the complete case analysis (HR 1.34 (95% CI 1.25–1.44), p Conclusions Being frail is associated with a significantly increased risk for ICU mortality in older patients, while being vulnerable alone did not significantly differ. New Frailty categories might reflect its “continuum” better and predict ICU outcome more accurately. Trial registration: Open Science Framework (OSF: https://osf.io/8buwk/). Graphical Abstract
Published: 2023
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2. Severe methodological problems in a recent review and analysis of the association between lithium concentration in potable water and suicide rates

Author: Plöderl, Martin, Naudet, Florian, Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre d'Investigation Clinique [Rennes] (CIC), and Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: [SDV]Life Sciences [q-bio]
Abstract: International audience
Published: 2023
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3. Accelerating clinical trial implementation in the context of the COVID-19 pandemic: challenges, lessons learned and recommendations from DisCoVeRy and the EU-SolidAct EU response group

Author: Alpha Diallo, Marius Trøseid, Victoria Charlotte Simensen, Anaïs Boston, Jacques Demotes, Inge Christoffer Olsen, Florence Chung, José Artur Paiva, Maya Hites, Florence Ader, Jose Ramon Arribas, Andreas Baratt-Due, Øyvind Melien, Evelina Tacconelli, Thèrèse Staub, Richard Greil, Sotirios Tsiodras, Matthias Briel, Hélène Esperou, France Mentré, Joe Eustace, Juliette Saillard, Christelle Delmas, Soizic LeMestre, Marina Dumousseaux, Dominique Costagliola, John-Arne Røttingen, Yazdan Yazdanpanah, Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Oslo University Hospital [Oslo], European Clinical Research Infrastructures Network [Dusseldorf] (ECRIN), Hospital de São João [Porto], Université libre de Bruxelles (ULB), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), La Paz University Hospital, Norwegian Institute of Public Health [Oslo] (NIPH), Università degli studi di Verona = University of Verona (UNIVR), Centre Hospitalier de Luxembourg [Luxembourg] (CHL), Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), National and Kapodistrian University of Athens (NKUA), University Hospital Basel [Basel], Pôle de Recherche Clinique [Paris] (PRC), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University College Cork (UCC), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CIC - CHU Bichat, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord
Subjects: Microbiology (medical), Medical education, Coronavirus disease 2019 (COVID-19), Adaptive Clinical Trials as Topic, EU-RESPOSE, Financial hurdles, Legal hurdles, Platform trials, Regulatory hurdles, MEDLINE, COVID-19, Context (language use), General Medicine, Clinical trial, Infectious Diseases, Political science, Pandemic, Commentary, Government Regulation, Humans, European Union, Pandemics, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Published: 2022
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4. Consensus Statement on the definition and classification of metabolic hyperferritinaemia

Author: Luca Valenti, Elena Corradini, Leon A. Adams, Elmar Aigner, Saleh Alqahtani, Marco Arrese, Edouard Bardou-Jacquet, Elisabetta Bugianesi, Jose-Manuel Fernandez-Real, Domenico Girelli, Hannes Hagström, Benjamin Henninger, Kris Kowdley, Guido Ligabue, Donald McClain, Fabrice Lainé, Koji Miyanishi, Martina U. Muckenthaler, Alessia Pagani, Patrizia Pedrotti, Antonello Pietrangelo, Daniele Prati, John D. Ryan, Laura Silvestri, C. Wendy Spearman, Per Stål, Emmanuel A. Tsochatzis, Francesca Vinchi, Ming-Hua Zheng, Heinz Zoller, Università degli Studi di Milano = University of Milan (UNIMI), Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), The University of Western Australia (UWA), Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Johns Hopkins University (JHU), Pontificia Universidad Católica de Chile (UC), 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], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Università degli studi di Torino = University of Turin (UNITO), Universitat de Girona [Girona], Universitat de Girona (UdG), Università degli studi di Verona = University of Verona (UNIVR), Karolinska University Hospital [Stockholm], Leopold Franzens Universität Innsbruck - University of Innsbruck, Washington State University (WSU), Wake Forest School of Medicine [Winston-Salem], Wake Forest Baptist Medical Center, Sapporo Medical University School of Medicine, Sapporo Medical University, Heidelberg University, IRCCS Ospedale San Raffaele [Milan, Italy], ASST Great Metropolitan Niguarda / ASST Grande Ospedale Metropolitano Niguarda [Milan, Italia], Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Royal College of Surgeons in Ireland (RCSI), University of Cape Town, University College of London [London] (UCL), Weill Cornell Medicine [New York], The First Affiliated Hospital of Wenzhou Medical University [Wenzhou, China], Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Ministero della Salute, Ricerca Finalizzata RF-2016-02364358, RC Rete cardiologica ‘CV PREVITAL’, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico ‘Liver BIBLE’ (PR-0391), Innovative Medicines Initiative 2 joint undertaking of European Union’s Horizon 2020 research and innovation programme and EFPIA European Union (EU) Programme Horizon 2020 (under grant agreement No. 777377) for the project LITMUS, H2020 under grant agreement ‘101016726’, the European Union, programme ‘Photonics’ under grant agreement ‘101016726’ for L.V. Fondo Nacional de Ciencia y Tecnología de Chile (FONDECYT #1191145 to M.A.) and from the Agencia Nacional de Investigación y Desarrollo, ANID through ANID ACE 210009 grant for M.A. NIH (P30DK124723), and Veterans Administration (2I01 BX001140) for D.M. SFB1036, SFB1118 and DFG (FerrOs — FOR5146, SPP2306) as well as Marsilius Kolleg for M.U.M. National Natural Science Foundation of China (82070588), High Level Creative Talents from Department of Public Health in Zhejiang Province (S2032102600032) for M.-H.Z. Swedish Cancer Society (170690) and Stockholm County Council (K2017-4579) for P.S., Jonchère, Laurent, Weill Cornell Medicine [Cornell University], and Cornell University [New York]
Subjects: [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, iron, Endocrinology, iron, hyperferritinemia, metabolic syndrome, Endocrinology, Diabetes and Metabolism, hyperferritinemia, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, metabolic syndrome
Abstract: International audience; Hyperferritinaemia is a common laboratory finding that is often associated with metabolic dysfunction and fatty liver. Metabolic hyperferritinaemia reflects alterations in iron metabolism that facilitate iron accumulation in the body and is associated with an increased risk of cardiometabolic and liver diseases. Genetic variants that modulate iron homeostasis and tissue levels of iron are the main determinants of serum levels of ferritin in individuals with metabolic dysfunction, raising the hypothesis that iron accumulation might be implicated in the pathogenesis of insulin resistance and the related organ damage. However, validated criteria for the non-invasive diagnosis of metabolic hyperferritinaemia and the staging of iron overload are still lacking, and there is no clear evidence of a benefit for iron depletion therapy. Here, we provide an overview of the literature on the relationship between hyperferritinaemia and iron accumulation in individuals with metabolic dysfunction, and on the associated clinical outcomes. We propose an updated definition and a provisional staging system for metabolic hyperferritinaemia, which has been agreed on by a multidisciplinary global panel of expert researchers. The goal is to foster studies into the epidemiology, genetics, pathophysiology, clinical relevance and treatment of metabolic hyperferritinaemia, for which we provide suggestions on the main unmet needs, optimal design and clinically relevant outcomes.
Published: 2023
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5. The relationship between glucose and the liver-alpha cell axis – A systematic review

Author: Thomas Pixner, Nathalie Stummer, Anna Maria Schneider, Andreas Lukas, Karin Gramlinger, Valérie Julian, David Thivel, Katharina Mörwald, Harald Mangge, Christopher Dalus, Elmar Aigner, Dieter Furthner, Daniel Weghuber, Katharina Maruszczak, Salzkammergutklinikum Voecklabruck, Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Laboratory of Metabolic Adaptations to Exercise in Physiological and Pathological Conditions, Université Blaise Pascal - Clermont-Ferrand 2 (UBP), and Medical University Graz
Subjects: pediatric, glucagon, Endocrinology, Diabetes and Metabolism, OGTT, glucose, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, liver-alpha cell axis, liver
Abstract: Until recently, glucagon was considered a mere antagonist to insulin, protecting the body from hypoglycemia. This notion changed with the discovery of the liver-alpha cell axis (LACA) as a feedback loop. The LACA describes how glucagon secretion and pancreatic alpha cell proliferation are stimulated by circulating amino acids. Glucagon in turn leads to an upregulation of amino acid metabolism and ureagenesis in the liver. Several increasingly common diseases (e.g., non-alcoholic fatty liver disease, type 2 diabetes, obesity) disrupt this feedback loop. It is important for clinicians and researchers alike to understand the liver-alpha cell axis and the metabolic sequelae of these diseases. While most of previous studies have focused on fasting concentrations of glucagon and amino acids, there is limited knowledge of their dynamics after glucose administration. The authors of this systematic review applied PRISMA guidelines and conducted PubMed searches to provide results of 8078 articles (screened and if relevant, studied in full). This systematic review aims to provide better insight into the LACA and its mediators (amino acids and glucagon), focusing on the relationship between glucose and the LACA in adult and pediatric subjects.
Published: 2023
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6. 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: Mercier, Noémie, Belhadi, Drifa, Dechanet, Aline, Delmas, Christelle, Saillard, Juliette, Dumousseaux, Marina, Le Mestre, Soizic, Fougerou-Leurent, Claire, Ferrane, Assia, Burdet, Charles, Espérou, Hélène, Ader, Florence, Hites, Maya, Peiffer-Smadja, Nathan, Poissy, Julien, Andrejak, Claire, Paiva, José Artur, Tacconelli, Evelina, Staub, Thérèse, Greil, Richard, Costagliola, Dominique, Mentre, France, Yazdanpanah, Yazdan, Diallo, Alpha, ANRS France Recherche Nord & sud Sida-hiv hépatites, 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, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Institut de Santé Publique, Université de Médecine Carol Davila, 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), Pôle de Recherche Clinique [Paris] (PRC), 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), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), CHU Lille, CHU Amiens-Picardie, Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Hospital de São João [Porto], Universitätsklinikum Tübingen - University Hospital of Tübingen, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Centre Hospitalier de Luxembourg [Luxembourg] (CHL), and Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU)
Subjects: EU-RESPONSE, [SDV]Life Sciences [q-bio], pharmacovigilance, adverse event, COVID-19, pandemic crisis
Abstract: International audience; 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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7. Premature Ovarian Insufficiency in CLPB Deficiency: Transcriptomic, Proteomic and Phenotypic Insights

Author: Elena J Tucker, Megan J Baker, Daniella H Hock, Julia T Warren, Sylvie Jaillard, Katrina M Bell, Rajini Sreenivasan, Shabnam Bakhshalizadeh, Chloe A Hanna, Nikeisha J Caruana, Saskia B Wortmann, Shamima Rahman, Robert D S Pitceathly, Jean Donadieu, Aurelia Alimi, Vincent Launay, Paul Coppo, Sophie Christin-Maitre, Gorjana Robevska, Jocelyn van den Bergen, Brianna L Kline, Katie L Ayers, Phoebe N Stewart, David A Stroud, Diana Stojanovski, Andrew H Sinclair, University of Melbourne, Murdoch Children's Research Institute (MCRI), Durham University, Washington University School of Medicine [Saint Louis, MO], Service de Cytogénétique et de Biologie Cellulaire, Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Royal Children's Hospital Melbourne, Victoria University [Melbourne], Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Amalia Children’s Hospital [Nijmegen, The Netherlands], Great Ormond Street Hospital for Children NHS Foundation Trust [London, UK] (GOSHC), UCL Institute of Neurology, Queen Square [London], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU de Saint-Brieuc, CHU Saint-Antoine [AP-HP], Sorbonne Université (SU), Royal Hobart Hospital, and This work was supported by an National Health and Medical Research Council (NHMRC) program grant (1074258 toA.H.S.), NHMRC grant (1140906 to D.A.S.), NHMRC fellowships (1054432 to E.J.T., 1126995 to R.S., 2009732 to D.A.S., 1062854 to A.H.S.), a Suzi Carp postdoctoral scholarship (to E.J.T.), a CHU Rennes grant (Appel à Projets Innovations 2019 to S.J.), an Australian Government Research Training Program scholarship (to M.J.B.), the Australian Mito Foundation for provision of instrumentation, incubator grants (to E.J.T. and D.S.), a Booster grant (to D.S.) and PhD Top-up scholarships (to M.J.B. and D.H.H.), and a Medical Research Council (UK) Clinician Scientist Fellowship (MR/S002065/1 to R.D.S.P.). S.B.W. was funded by ERAPERMED2019-310—Personalized Mitochondrial Medicine (PerMiM): Optimizing diagnostics and treatment for patients with mitochondrial diseases (FWF 4704-B).
Subjects: Proteomics, premature ovarian insufficiency, Neutropenia, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, primary mitochondrial disease, Biochemistry (medical), Clinical Biochemistry, Menopause, Premature, Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6], Endopeptidase Clp, Primary Ovarian Insufficiency, Biochemistry, Cataract, mitochondria, Endocrinology, Phenotype, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, CLPB, Humans, genetics, Female, infertility, Transcriptome
Abstract: Context Premature ovarian insufficiency (POI) is a common form of female infertility that usually presents as an isolated condition but can be part of various genetic syndromes. Early diagnosis and treatment of POI can minimize comorbidity and improve health outcomes. Objective We aimed to determine the genetic cause of syndromic POI, intellectual disability, neutropenia, and cataracts. Methods We performed whole-exome sequencing (WES) followed by functional validation via RT-PCR, RNAseq, and quantitative proteomics, as well as clinical update of previously reported patients with variants in the caseinolytic peptidase B (CLPB) gene. Results We identified causative variants in CLPB, encoding a mitochondrial disaggregase. Variants in this gene are known to cause an autosomal recessive syndrome involving 3-methylglutaconic aciduria, neurological dysfunction, cataracts, and neutropenia that is often fatal in childhood; however, there is likely a reporting bias toward severe cases. Using RNAseq and quantitative proteomics we validated causation and gained insight into genotype:phenotype correlation. Clinical follow-up of patients with CLPB deficiency who survived to adulthood identified POI and infertility as a common postpubertal ailment. Conclusion A novel splicing variant is associated with CLPB deficiency in an individual who survived to adulthood. POI is a common feature of postpubertal female individuals with CLPB deficiency. Patients with CLPB deficiency should be referred to pediatric gynecologists/endocrinologists for prompt POI diagnosis and hormone replacement therapy to minimize associated comorbidities.
Published: 2022
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8. The Role of Macronutrients in the Pathogenesis, Prevention and Treatment of Non-Alcoholic Fatty Liver Disease (NAFLD) in the Paediatric Population—A Review

Author: Thomas Pixner, Nathalie Stummer, Anna Maria Schneider, Andreas Lukas, Karin Gramlinger, Valérie Julian, David Thivel, Katharina Mörwald, Katharina Maruszczak, Harald Mangge, Julian Gomahr, Daniel Weghuber, Dieter Furthner, Salzkammergutklinikum Voecklabruck, Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Laboratory of Metabolic Adaptations to Exercise in Physiological and Pathological Conditions, Université Blaise Pascal - Clermont-Ferrand 2 (UBP), and Medical University Graz
Subjects: obesity, paediatric, macronutrients, carbohydrates, Paleontology, non-alcoholic fatty liver disease, General Biochemistry, Genetics and Molecular Biology, nutrition, Space and Planetary Science, NAFLD, fat, protein, diet, Ecology, Evolution, Behavior and Systematics, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Paediatric non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in childhood. Obesity is the main risk factor. Nutrition and lifestyle are the key elements in preventing and treating NAFLD in the absence of approved drug therapy. Whilst recommendations and studies on macronutrients (carbohydrates, fat and protein) in adult NAFLD exist, the discussion of this topic in paediatric NAFLD remains contradictory. The purpose of this review is to provide state-of-the-art knowledge on the role of macronutrients in paediatric NAFLD regarding quality and quantity. PubMed was searched and original studies and review articles were included in this review. Fructose, sucrose, saturated fatty acids, trans-fatty acids and ω-6-fatty-acids are strongly associated with paediatric NAFLD. High consumption of fibre, diets with a low glycaemic index, mono-unsaturated-fatty-acids and ω-3-fatty-acids reduce the risk of childhood-onset NAFLD. Data regarding the role of dietary protein in NAFLD are contradictory. No single diet is superior in treating paediatric NAFLD, although the composition of macronutrients in the Mediterranean Diet appears beneficial. Moreover, the optimal proportions of total macronutrients in the diet of paediatric NAFLD patients are unknown. Maintaining a eucaloric diet and avoiding saturated fatty acids, simple sugars (mainly fructose) and a high-caloric Western Diet are supported by literature.
Published: 2022
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9. The serum metabolome mediates the concert of diet, exercise, and neurogenesis, determining the risk for cognitive decline and dementia

Author: Claudine Manach, Cristina Andres-Lacueva, Cécile Proust-Lima, Cécile Delcourt, Vikki Houghton, Barbara Altendorfer, Cécilia Samieri, Alex Sánchez-Pla, Ludwig Aigner, Chiara De Lucia, Sandrine Thuret, Aniko Korosi, Paul J. Lucassen, Dorrain Y Low, Mireia Urpi-Sarda, Andrea Du Preez, Sophie Lefèvre-Arbogast, Raúl González-Domínguez, Catherine Féart, Mercè Pallàs, Catherine Helmer, Silvie R. Ruigrok, Structural and Functional Plasticity of the nervous system (SILS, FNWI), King‘s College London, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Barcelona, University of Amsterdam [Amsterdam] (UvA), Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Instituto de Salud Carlos III [Madrid] (ISC), Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Technische Universität Dresden = Dresden University of Technology (TU Dresden), Instituto de Salud Carlos III, Agence Nationale de la Recherche, ANR-15-HDHL-0002,D-CogPlast,Identification of dietary modulators of cognitive ageing and brain plasticity and proof of concept of efficacy for preventing-reversing cognitive decline(2015), Admin, Oskar, and Identification of dietary modulators of cognitive ageing and brain plasticity and proof of concept of efficacy for preventing-reversing cognitive decline - - D-CogPlast2015 - ANR-15-HDHL-0002 - JPI HDHL - VALID
Subjects: medicine.medical_specialty, Epidemiology, Neurogenesis, Cognitive decline, Hippocampal formation, Hippocampus, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Developmental Neuroscience, Internal medicine, mental disorders, medicine, Metabolome, Dementia, Humans, Cognitive Dysfunction, Progenitor cell, Pathological, Exercise, 030304 developmental biology, 0303 health sciences, business.industry, Health Policy, medicine.disease, 3. Good health, Diet, Psychiatry and Mental health, Endocrinology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Apoptosis, Adult hippocampal neurogenesis, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology (clinical), Geriatrics and Gerontology, business, 030217 neurology & neurosurgery
Abstract: International audience; Introduction: Diet and exercise influence the risk of cognitive decline (CD) and dementia through the food metabolome and exercise-triggered endogenous factors, which use the blood as a vehicle to communicate with the brain. These factors might act in concert with hippocampal neurogenesis (HN) to shape CD and dementia.Methods: Using an in vitro neurogenesis assay, we examined the effects of serum samples from a longitudinal cohort (n = 418) on proxy HN readouts and their association with future CD and dementia across a 12-year period.Results: Altered apoptosis and reduced hippocampal progenitor cell integrity were associated with exercise and diet and predicted subsequent CD and dementia. The effects of exercise and diet on CD specifically were mediated by apoptosis.Discussion: Diet and exercise might influence neurogenesis long before the onset of CD and dementia. Alterations in HN could signify the start of the pathological process and potentially represent biomarkers for CD and dementia.
Published: 2022
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10. Association between tracheostomy timing and outcomes for older critically ill COVID-19 patients:prospective observational study in European intensive care units

Author: Raphael Romano Bruno, Bertrand Guidet, Michael Beil, Peter Vernon van Heerden, Kamil Polok, Bernardo Bollen Pinto, Bernhard Wernly, Finn H. Andersen, Antonio Artigas, Michael Joannidis, Wojciech Szczeklik, Brian Marsh, Rui Moreno, Dorota Studzińska, Maurizio Cecconi, Joerg C. Schefold, Hans Flaatten, Sigal Sviri, Sandra Oeyen, Dylan W. de Lange, Jakub Fronczek, Jesper Fjølner, Christian Jung, Susannah Leaver, Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), The Hebrew University of Jerusalem (HUJ), University of Bergen (UiB), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Réanimation Médicale [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), University Medical Center [Utrecht], Aarhus University Hospital, St George’s University Hospitals, Hadassah Hebrew University Medical Center [Jerusalem], Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), CIBER de Epidemiología y Salud Pública (CIBERESP), Hôpitaux Universitaires de Genève (HUG), Bern University Hospital [Berne] (Inselspital), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Ghent University Hospital, Mater Misericordiae University Hospital (The Mater Hospital), Norwegian University of Science and Technology (NTNU), NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Humanitas University [Milan] (Hunimed), and Gestionnaire, Hal Sorbonne Université
Subjects: Male, medicine.medical_specialty, Time Factors, Critical Care, Coronavirus disease 2019 (COVID-19), intensive care units, Critical Illness, medicine.medical_treatment, [SDV]Life Sciences [q-bio], tracheostomy, mechanical ventilation, law.invention, law, Intensive care, medicine, Humans, Intubation, Prospective Studies, Clinical Investigation, Correlation of Data, 610 Medicine & health, Prospective cohort study, outcome assessment, Aged, Mechanical ventilation, business.industry, Critically ill, COVID-19, healthcare, Length of Stay, Respiration, Artificial, Intensive care unit, Europe, Survival Rate, Health Care, [SDV] Life Sciences [q-bio], Treatment Outcome, Anesthesiology and Pain Medicine, Emergency medicine, Female, Observational study, business
Abstract: BACKGROUND Tracheostomy is performed in patients expected to require prolonged mechanical ventilation, but to date optimal timing of tracheostomy has not been established. The evidence concerning tracheostomy in COVID-19 patients is particularly scarce. We aimed to describe the relationship between early tracheostomy (��10 days since intubation) and outcomes for patients with COVID-19. METHODS This was a prospective cohort study performed in 152 centres across 16 European countries from February to December 2020. We included patients aged ��70 yr with confirmed COVID-19 infection admitted to an intensive care unit, requiring invasive mechanical ventilation. Multivariable analyses were performed to evaluate the association between early tracheostomy and clinical outcomes including 3-month mortality, intensive care length of stay, and duration of mechanical ventilation. RESULTS The final analysis included 1740 patients with a mean age of 74 yr. Tracheostomy was performed in 461 (26.5%) patients. The tracheostomy rate varied across countries, from 8.3% to 52.9%. Early tracheostomy was performed in 135 (29.3%) patients. There was no difference in 3-month mortality between early and late tracheostomy in either our primary analysis (hazard ratio [HR]=0.96; 95% confidence interval [CI], 0.70-1.33) or a secondary landmark analysis (HR=0.78; 95% CI, 0.57-1.06). CONCLUSIONS There is a wide variation across Europe in the timing of tracheostomy for critically ill patients with COVID-19. However, we found no evidence that early tracheostomy is associated with any effect on survival amongst older critically ill patients with COVID-19. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov NCT04321265.
Published: 2022
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11. Association between alanine aminotransferase as surrogate of fatty liver disease and physical activity and sedentary time in adolescents with obesity

Author: Valérie Julian, Peter Bergsten, Gael Ennequin, Anders Forslund, Hakan Ahlstrom, Iris Ciba, Marie Dahlbom, Dieter Furthner, Julian Gomahr, Joel Kullberg, Katharina Maruszczak, Katharina Morwald, Roger Olsson, Thomas Pixner, Anna Schneider, Bruno Pereira, Suzanne Ring-Dimitriou, David Thivel, Daniel Weghuber, Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Uppsala Universitet [Uppsala], Laboratory of Metabolic Adaptations to Exercise in Physiological and Pathological Conditions, Université Blaise Pascal - Clermont-Ferrand 2 (UBP), Uppsala University Hospital, Antaros Medical AB [Mölndal Sweden] (BioVenture Hub), Salzkammergut-Klinikum, Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand, and Paris-Lodron-Universität Salzburg (PLUS)
Subjects: Male, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Pediatric Obesity, Adolescent, Physical activity, Alanine Transaminase, Cross-Sectional Studies, Liver, Non-alcoholic Fatty Liver Disease, Pediatrics, Perinatology and Child Health, Nonalcoholic fatty liver disease, Humans, Female, Aspartate Aminotransferases, Sedentary Behavior, Child, Exercise, Biomarkers
Abstract: To compare patterns of sedentary (SED) time (more sedentary, SED + vs less sedentary, SED-), moderate to vigorous physical activity (MVPA) time (more active, MVPA + vs less active, MVPA-), and combinations of behaviors (SED-/MVPA + , SED-/MVPA-, SED + /MVPA + , SED + /MVPA-) regarding nonalcoholic fatty liver diseases (NAFLD) markers. This cross-sectional study included 134 subjects (13.4 ± 2.2 years, body mass index (BMI) 98.9 ± 0.7 percentile, 48.5% females) who underwent 24-h/7-day accelerometry, anthropometric, and biochemical markers (alanine aminotransferase (ALT) as first criterion, and aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), AST/ALT ratio as secondary criteria). A subgroup of 39 patients underwent magnetic resonance imaging-liver fat content (MRI-LFC). Hepatic health was better in SED- (lower ALT, GGT, and MRI-LFC (p 0.05), higher AST/ALT (p 0.01)) vs SED + and in MVPA + (lower ALT (p 0.05), higher AST/ALT (p 0.01)) vs MVPA- groups after adjustment for age, gender, and Tanner stages. SED-/MVPA + group had the best hepatic health. SED-/MVPA- group had lower ALT and GGT and higher AST/ALT (p 0.05) in comparison with SED + /MVPA + group independently of BMI. SED time was positively associated with biochemical (high ALT, low AST/ALT ratio) and imaging (high MRI-LFC) markers independently of MVPA. MVPA time was associated with biochemical markers (low ALT, high AST/ALT) but these associations were no longer significant after adjustment for SED time.Lower SED time is associated with better hepatic health independently of MVPA. Reducing SED time might be a first step in the management of pediatric obesity NAFLD when increasing MVPA is not possible.• MVPA and SED times are associated with cardiometabolic risks in youths with obesity. • The relationships between NAFLD markers and concomitant MVPA and SED times have not been studied in this population.• Low SED time is associated with healthier liver enzyme profiles and LFC independent of MVPA. • While low SED/high MVPA is the more desirable pattern, low SED/low MVPA pattern would have healthier liver enzyme profile compared with high MVPA/high SED, independent of BMI, suggesting that reducing SED time irrespective of MVPA is needed to optimize liver health.
Published: 2022
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12. Sex-Specific Effects of Nutritional Supplements for Infants Born Early or Small: An Individual Participant Data Meta-Analysis (ESSENCE IPD-MA) II: Growth

Author: Luling Lin, Greg D. Gamble, Caroline A. Crowther, Frank H. Bloomfield, Massimo Agosti, Stephanie A. Atkinson, Augusto Biasini, Nicholas D. Embleton, Fernando Lamy Filho, Christoph Fusch, Maria L. Gianni, Hayriye Gözde Kanmaz Kutman, Winston Koo, Ita Litmanovitz, Colin Morgan, Kanya Mukhopadhyay, Erica Neri, Jean-Charles Picaud, Niels Rochow, Paola Roggero, Kenneth Stroemmen, Maw J. Tan, Francesco M. Tandoi, Claire L. Wood, Gitte Zachariassen, Jane E. Harding, CarMeN, laboratoire, University of Auckland [Auckland], Ospedale del Ponte [Varese, Italy], Universitá degli Studi dell’Insubria = University of Insubria [Varese] (Uninsubria), McMaster University [Hamilton, Ontario], Italian Association of Human Milk Banks [Milan, Italy] (AIBLUD), Newcastle University [Newcastle], Universidade Federal do Maranhão = Federal University of Maranhão (UFMA), Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Università degli Studi di Milano = University of Milan (UNIMI), Bilkent City Hospital = Ankara Şehir Hastanesi [Ankara, Turkey] (BCH), Wayne State University [Detroit], Meir Medical Center [Kfar Saba, Israel] (2MC), Liverpool Women's NHS Foundation Trust, Post Graduate Institute of Medical Education and Research [Chandigarh, India] (PGIMER), University of Bologna/Università di Bologna, 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 de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Oslo University Hospital [Oslo], Alder Hey Children's Hospital NHS Foundation Trust [Liverpool], Odense University Hospital (OUH), University of Southern Denmark (SDU), Lin L., Gamble G.D., Crowther C.A., Bloomfield F.H., Agosti M., Atkinson S.A., Biasini A., Embleton N.D., Filho F.L., Fusch C., Gianni M.L., Kutman H.G.K., Koo W., Litmanovitz I., Morgan C., Mukhopadhyay K., Neri E., Picaud J.-C., Rochow N., Roggero P., Stroemmen K., Tan M.J., Tandoi F.M., Wood C.L., Zachariassen G., and Harding J.E.
Subjects: Male, growth, [SDV]Life Sciences [q-bio], Growth, Sex Factor, macronutrient supplementation, Individual participants data meta-analysi, small-for-gestational-age infants, Follow-Up Studie, Body Mass Index, Sex Factors, systematic review, Bone Density, Humans, TX341-641, preterm infants, Infant Nutritional Physiological Phenomena, Dietary Supplement, Nutrition and Dietetics, Small-for-gestational-age infants, Nutrition. Foods and food supply, Small-for-gestational-age infant, Infant, Newborn, Individual participants data meta-analysis, Preterm infants, Macronutrient supplementation, Nutrients, Body Height, individual participants data meta-analysis, [SDV] Life Sciences [q-bio], Treatment Outcome, Preterm infant, Dietary Supplements, Infant, Small for Gestational Age, Systematic review, Female, Infant, Premature, Human, Nutrient, Food Science, Follow-Up Studies
Abstract: Neonatal nutritional supplements may improve early growth for infants born small, but effects on long-term growth are unclear and may differ by sex. We assessed the effects of early macronutrient supplements on later growth. We searched databases and clinical trials registers from inception to April 2019. Participant-level data from randomised trials were included if the intention was to increase macronutrient intake to improve growth or development of infants born preterm or small-for-gestational-age. Co-primary outcomes were cognitive impairment and metabolic risk. Supplementation did not alter BMI in childhood (kg/m2: adjusted mean difference (aMD) −0.11[95% CI −0.47, 0.25], p = 0.54; 3 trials, n = 333). Supplementation increased length (cm: aMD 0.37[0.01, 0.72], p = 0.04; 18 trials, n = 2008) and bone mineral content (g: aMD 10.22[0.52, 19.92], p = 0.04; 6 trials, n = 313) in infancy, but not at older ages. There were no differences between supplemented and unsupplemented groups for other outcomes. In subgroup analysis, supplementation increased the height z-score in male toddlers (aMD 0.20[0.02, 0.37], p = 0.03; 10 trials, n = 595) but not in females, and no significant sex interaction was observed (p = 0.21). Macronutrient supplementation for infants born small may not alter BMI in childhood. Supplementation increased growth in infancy, but these effects did not persist in later life. The effects did not differ between boys and girls.
Published: 2022
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13. Effect of Remdesivir on Viral Dynamics in COVID-19 Hospitalized Patients: A Modelling Analysis of the Randomized, Controlled, Open-Label DisCoVeRy Trial

Author: Guillaume Lingas, Nadège Néant, Alexandre Gaymard, Drifa Belhadi, Gilles Peytavin, Maya Hites, Thérèse Staub, Richard Greil, Jose-Artur Paiva, Julien Poissy, Nathan Peiffer-Smadja, Dominique Costagliola, Yazdan Yazdanpanah, Florent Wallet, Amandine Gagneux-Brunon, France Mentré, Florence Ader, Charles Burdet, Jérémie Guedj, Maude Bouscambert-Duchamp, 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), Hospices Civils de Lyon (HCL), Virology and human respiratory Pathologies - Virology and human respiratory Pathologies (VirPath), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), 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, Institut des Agents Infectieux [Lyon] (IAI), Centre National de Référence des Virus des Infections Respiratoires (dont la Grippe) [Lyon] (CNR - laboratoire associé), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université libre de Bruxelles (ULB), Centre Hospitalier de Luxembourg [Luxembourg] (CHL), Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Centro Hospitalar Universitário São João - Faculty of Medicine - University of Porto - Grupo de Infecção e Sepsis, Porto, 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), Services de Maladies Infectieuses et Tropicales [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imperial College London, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Emergence de la résistance bactérienne in vivo (EA3964), and Université Paris Diderot - Paris 7 (UPD7)
Subjects: Pharmacology, Microbiology (medical), Alanine, Infectious Diseases, SARS-CoV-2, Humans, Pharmacology (medical), Antiviral Agents, Adenosine Monophosphate, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, COVID-19 Drug Treatment
Abstract: Background The antiviral efficacy of remdesivir in COVID-19 hospitalized patients remains controversial. Objectives To estimate the effect of remdesivir in blocking viral replication. Methods We analysed nasopharyngeal normalized viral loads from 665 hospitalized patients included in the DisCoVeRy trial (NCT 04315948; EudraCT 2020-000936-23), randomized to either standard of care (SoC) or SoC + remdesivir. We used a mathematical model to reconstruct viral kinetic profiles and estimate the antiviral efficacy of remdesivir in blocking viral replication. Additional analyses were conducted stratified on time of treatment initiation (≤7 or >7 days since symptom onset) or viral load at randomization (< or ≥3.5 log10 copies/104 cells). Results In our model, remdesivir reduced viral production by infected cells by 2-fold on average (95% CI: 1.5–3.2-fold). Model-based simulations predict that remdesivir reduced time to viral clearance by 0.7 days compared with SoC, with large inter-individual variabilities (IQR: 0.0–1.3 days). Remdesivir had a larger impact in patients with high viral load at randomization, reducing viral production by 5-fold on average (95% CI: 2.8–25-fold) and the median time to viral clearance by 2.4 days (IQR: 0.9–4.5 days). Conclusions Remdesivir halved viral production, leading to a median reduction of 0.7 days in the time to viral clearance compared with SoC. The efficacy was larger in patients with high viral load at randomization.
Published: 2022
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14. Apolipoprotein E and sex modulate fatty acid metabolism in a prospective observational study of cognitive decline

Author: Raúl González-Domínguez, Pol Castellano-Escuder, Sophie Lefèvre-Arbogast, Dorrain Y. Low, Andrea Du Preez, Silvie R. Ruigrok, Hyunah Lee, Catherine Helmer, Mercè Pallàs, Mireia Urpi-Sarda, Alex Sánchez-Pla, Aniko Korosi, Paul J. Lucassen, Ludwig Aigner, Claudine Manach, Sandrine Thuret, Cécilia Samieri, Cristina Andres-Lacueva, Instituto de Salud Carlos III [Madrid] (ISC), Universitat de Barcelona (UB), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, University of Amsterdam [Amsterdam] (UvA), University of Barcelona, Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Agence Nationale de la Recherche, Instituto de Salud Carlos III, Institut National de la Santé et de la Recherche Médicale, Université de Bordeaux, Fondation pour la Recherche Médicale, Mutuelle Générale de l'Education Nationale, Conseil Régional Aquitaine, Conseil régional de Bourgogne-Franche-Comté, Caisse nationale de solidarité pour l'autonomie, ANR-15-HDHL-0002,D-CogPlast,Identification of dietary modulators of cognitive ageing and brain plasticity and proof of concept of efficacy for preventing-reversing cognitive decline(2015), ANR-17-EURE-0019,DPH,University of Bordeaux Graduate School in Digital Public Health(2017), ANR-06-PNRA-0005,COGINUT,COGINUT : Cognition, anti-oxydants, acides gras: approche interdisciplinaire du rôle de la nutrition dans le vieillissement du cerveau(2006), European Project: 277673,EC:FP7:KBBE,FP7-JPROG-2011-RTD,HDHL CSA(2011), European Project: 821522 ,PLASLTINHIB, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Structural and Functional Plasticity of the nervous system (SILS, FNWI), Admin, Oskar, Identification of dietary modulators of cognitive ageing and brain plasticity and proof of concept of efficacy for preventing-reversing cognitive decline - - D-CogPlast2015 - ANR-15-HDHL-0002 - JPI HDHL - VALID, University of Bordeaux Graduate School in Digital Public Health - - DPH2017 - ANR-17-EURE-0019 - EURE - VALID, Programme National de Recherches en Alimentation et Nutrition Humaine (PNRA) - COGINUT : Cognition, anti-oxydants, acides gras: approche interdisciplinaire du rôle de la nutrition dans le vieillissement du cerveau - - COGINUT2006 - ANR-06-PNRA-0005 - PNRA - VALID, A Healthy Diet for a Healthy Life - Coordination Action - HDHL CSA - - EC:FP7:KBBE2011-05-01 - 2015-07-31 - 277673 - VALID, and Investissement d'avenir - PLASLTINHIB - 821522 - INCOMING
Subjects: Male, Genotype, Cognitive Neuroscience, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Apolipoprotein E4, Cognitive decline, Neurosciences. Biological psychiatry. Neuropsychiatry, Neuropsychological Tests, Sex Factors, Metabolites, Humans, Metabolomics, Cognitive Dysfunction, Prospective Studies, Fatty acids, RC346-429, Alleles, Acyl-carnitines, Research, Biochemical markers, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Metabòlits, Neurology, Metabolòmica, Case-Control Studies, Marcadors bioquímics, Female, Sex, Neurology (clinical), Neurology. Diseases of the nervous system, Apolipoprotein E, [SDV.NEU.SC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, RC321-571
Abstract: Background Fatty acids play prominent roles in brain function as they participate in structural, metabolic and signaling processes. The homeostasis of fatty acids and related pathways is known to be impaired in cognitive decline and dementia, but the relationship between these metabolic disturbances and common risk factors, namely the ɛ4 allele of the apolipoprotein E (ApoE-ɛ4) gene and sex, remains elusive. Methods In order to investigate early alterations associated with cognitive decline in the fatty acid-related serum metabolome, we here applied targeted metabolomics analysis on a nested case-control study (N=368), part of a prospective population cohort on dementia. Results When considering the entire study population, circulating levels of free fatty acids, acyl-carnitines and pantothenic acid were found to be increased among those participants who had greater odds of cognitive decline over a 12-year follow-up. Interestingly, stratified analyses indicated that these metabolomic alterations were specific for ApoE-ɛ4 non-carriers and women. Conclusions Altogether, our results highlight that the regulation of fatty acids and related metabolic pathways during ageing and cognitive decline depends on complex inter-relationships between the ApoE-ε4 genotype and sex. A better understanding of the ApoE-ɛ4 and sex dependent modulation of metabolism is essential to elucidate the individual variability in the onset of cognitive decline, which would help develop personalized therapeutic approaches.
Published: 2022
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15. Sedentary time has a stronger impact on metabolic health than moderate to vigorous physical activity in adolescents with obesity: a cross-sectional analysis of the Beta-JUDO study

Author: Valérie Julian, Peter Bergsten, Anders Forslund, Hakan Ahlstrom, Iris Ciba, Marie Dahlbom, Dieter Furthner, Julian Gomahr, Joel Kullberg, Katharina Maruszczak, Katharina Morwald, Roger Olsson, Thomas Pixner, Anna Schneider, Bruno Pereira, David Thivel, Daniel Weghuber, Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Uppsala Universitet [Uppsala], Antaros Medical AB [Mölndal Sweden] (BioVenture Hub), Salzkammergut-Klinikum, Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand, Laboratory of Metabolic Adaptations to Exercise in Physiological and Pathological Conditions, and Université Blaise Pascal - Clermont-Ferrand 2 (UBP)
Subjects: Male, body composition, metabolic health, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Pediatric Obesity, Nutrition and Dietetics, Adolescent, Health Policy, sedentary time, Cholesterol, HDL, Public Health, Environmental and Occupational Health, physical activity, Body Mass Index, Cross-Sectional Studies, Pediatrics, Perinatology and Child Health, Humans, Female, Insulin Resistance, Sedentary Behavior, Waist Circumference, Child, childhood obesity, Exercise, Martial Arts
Abstract: International audience; Background Relationships between movement-related behaviours and metabolic health remain underexplored in adolescents with obesity. Objectives To compare profiles of sedentary time (more sedentary, SED+ vs. less sedentary, SED-), moderate to vigorous physical activity (MVPA) time (more active, MVPA+ vs. less active, MVPA-) and combinations of behaviours (SED-/MVPA+, SED-/MVPA-, SED+/MVPA+, SED+/MVPA-) in regard to metabolic health. Methods One hundred and thirty-four subjects (mean age 13.4 +/- 2.2 yrs, mean body mass index [BMI] 98.9 +/- 0.7 percentile, 48.5% females) underwent 24 h/7 day accelerometry, anthropometric, body composition, blood pressure (BP), lipid profile and insulin resistance (IR) assessments. Results Metabolic health was better in SED- [lower fat mass (FM) percentage (p < 0.05), blood pressure (BP) (p < 0.05), homeostasis model assessment of insulin resistance (HOMA-IR) (p < 0.001) and metabolic syndrome risk score (MetScore) (p < 0.001), higher high-density lipoprotein-cholesterol (HDL-c) (p = 0.001)] vs. SED+ group and in MVPA+ [lower triglyceridemia (TG), (p < 0.05), HOMA-IR (p < 0.01) and MetScore (p < 0.001), higher HDL-c (p < 0.01)] vs. MVPA- group after adjustment with age, gender, maturation and BMI. SED-/MVPA+ group had the best metabolic health. While sedentary (p < 0.001) but also MVPA times (p < 0.001) were lower in SED-/MVPA- vs. SED+/MVPA+, SED-/MVPA- had lower FM percentage (p < 0.05), HOMA-IR (p < 0.01) and MetScore (p < 0.05) and higher HDL-c (p < 0.05), independently of BMI. Sedentary time was positively correlated with HOMA-IR and Metscore and negatively correlated with HDL-c after adjustment with MVPA (p < 0.05). MVPA was negatively correlated with HOMA-IR, BP and MetScore and positively correlated with HDL-c after adjustment with sedentary time (p < 0.05). Conclusion Lower sedentary time is associated with a better metabolic health independently of MVPA and might be a first step in the management of pediatric obesity when increasing MVPA is not possible.
Published: 2021
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16. Frequent SLC35A2 brain mosaicism in mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE)

Author: Stéphanie Baulac, Eleonora Aronica, Georg Dorfmüller, Till Hartlieb, Roland Coras, Ingmar Blümcke, Sara Baldassari, Se Hoon Kim, Mathilde Chipaux, Thomas Bonduelle, Nam Suk Sim, Katja Kobow, Hoon Chul Kang, Homa Adle-Biassette, Jeong Ho Lee, Pathology, APH - Aging & Later Life, APH - Mental Health, ANS - Cellular & Molecular Mechanisms, Gestionnaire, Hal Sorbonne Université, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Korea Advanced Institute of Science and Technology (KAIST), Yonsei University, Universitätsklinikum Erlangen [Erlangen], Fondation Ophtalmologique Adolphe de Rothschild [Paris], Maladies neurodéveloppementales et neurovasculaires (NeuroDiderot (UMR_S_1141 / U1141)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service d′Anatomie et de Cytologie Pathologiques [Lariboisiere], Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Amsterdam [Amsterdam] (UvA), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)
Subjects: Male, 0301 basic medicine, Drug Resistant Epilepsy, Pathology, Neurology, Glycosylation, Somatic cell, [SDV]Life Sciences [q-bio], lcsh:RC346-429, Neurosurgical Procedures, Epilepsy, 0302 clinical medicine, Child, Mosaicism, Brain, Hyperplasia, 3. Good health, Brain mosaicism, [SDV] Life Sciences [q-bio], Oligodendroglia, medicine.anatomical_structure, Child, Preschool, Female, medicine.medical_specialty, Malformations of cortical development, Adolescent, Monosaccharide Transport Proteins, Biology, Focal cortical dysplasia, Pathology and Forensic Medicine, White matter, Young Adult, 03 medical and health sciences, Cellular and Molecular Neuroscience, medicine, Humans, ddc:610, Progenitor cell, lcsh:Neurology. Diseases of the nervous system, SLC35A2 gene, Research, Infant, medicine.disease, 030104 developmental biology, Genetic marker, Epilepsies, Partial, Neurology (clinical), Congenital disorder of glycosylation, 030217 neurology & neurosurgery
Abstract: Focal malformations of cortical development (MCD) are linked to somatic brain mutations occurring during neurodevelopment. Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) is a newly recognized clinico-pathological entity associated with pediatric drug-resistant focal epilepsy, and amenable to neurosurgical treatment. MOGHE is histopathologically characterized by clusters of increased oligodendroglial cell densities, patchy zones of hypomyelination, and heterotopic neurons in the white matter. The molecular etiology of MOGHE remained unknown so far. We hypothesized a contribution of mosaic brain variants and performed deep targeted gene sequencing on 20 surgical MOGHE brain samples from a single-center cohort of pediatric patients. We identified somatic pathogenic SLC35A2 variants in 9/20 (45%) patients with mosaic rates ranging from 7 to 52%. SLC35A2 encodes a UDP-galactose transporter, previously implicated in other malformations of cortical development (MCD) and a rare type of congenital disorder of glycosylation. To further clarify the histological features of SLC35A2-brain tissues, we then collected 17 samples with pathogenic SLC35A2 variants from a multicenter cohort of MCD cases. Histopathological reassessment including anti-Olig2 staining confirmed a MOGHE diagnosis in all cases. Analysis by droplet digital PCR of pools of microdissected cells from one MOGHE tissue revealed a variant enrichment in clustered oligodendroglial cells and heterotopic neurons. Through an international consortium, we assembled an unprecedented series of 26 SLC35A2-MOGHE cases providing evidence that mosaic SLC35A2 variants, likely occurred in a neuroglial progenitor cell during brain development, are a genetic marker for MOGHE.
Published: 2021
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17. Sex-Specific Effects of Nutritional Supplements for Infants Born Early or Small: An Individual Participant Data Meta-Analysis (ESSENCE IPD-MA) I-Cognitive Function and Metabolic Risk

Author: Luling Lin, Greg D. Gamble, Caroline A. Crowther, Frank H. Bloomfield, Massimo Agosti, Stephanie A. Atkinson, Augusto Biasini, Nicholas D. Embleton, Mary S. Fewtrell, Fernando Lamy-Filho, Christoph Fusch, Maria L. Gianni, H. Gozde Kanmaz Kutman, Winston Koo, Ita Litmanovitz, Colin Morgan, Kanya Mukhopadhyay, Erica Neri, Jean-Charles Picaud, Niels Rochow, Paola Roggero, Atul Singhal, Kenneth Stroemmen, Maw J. Tan, Francesco M. Tandoi, Claire L. Wood, Gitte Zachariassen, Jane E. Harding, CarMeN, laboratoire, University of Auckland [Auckland], Ospedale del Ponte [Varese, Italy], McMaster University [Hamilton, Ontario], Italian Association of Human Milk Banks [Milan, Italy] (AIBLUD), Newcastle University [Newcastle], Great Ormond Street Institute of Child Health (UCL), University College of London [London] (UCL), Universidade Federal do Maranhão = Federal University of Maranhão (UFMA), Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Università degli Studi di Milano = University of Milan (UNIMI), Bilkent City Hospital = Ankara Şehir Hastanesi [Ankara, Turkey] (BCH), Wayne State University [Detroit], Meir Medical Center [Kfar Saba, Israel] (2MC), Liverpool Women's NHS Foundation Trust, Post Graduate Institute of Medical Education and Research [Chandigarh, India] (PGIMER), University of Bologna/Università di Bologna, 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 de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Institute of Child Health [London], Oslo University Hospital [Oslo], Alder Hey Children's Hospital NHS Foundation Trust [Liverpool], Odense University Hospital (OUH), University of Southern Denmark (SDU), Lin L., Gamble G.D., Crowther C.A., Bloomfield F.H., Agosti M., Atkinson S.A., Biasini A., Embleton N.D., Fewtrell M.S., Lamy-Filho F., Fusch C., Gianni M.L., Gozde Kanmaz Kutman H., Koo W., Litmanovitz I., Morgan C., Mukhopadhyay K., Neri E., Picaud J.-C., Rochow N., Roggero P., Singhal A., Stroemmen K., Tan M.J., Tandoi F.M., Wood C.L., Zachariassen G., and Harding J.E.
Subjects: Male, [SDV]Life Sciences [q-bio], macronutrient supplementation, Individual participants data meta-analysi, Cognition, Pregnancy, small-for gestational-age infants, Humans, TX341-641, Cognitive Dysfunction, Metabolic risk, preterm infants, cognitive function, Nutrition and Dietetics, Nutrition. Foods and food supply, Small-for gestational-age infant, Infant, Newborn, Parturition, Individual participants data meta-analysis, Preterm infants, Infant, Macronutrient supplementation, Small-for gestational-age infants, individual participants data meta-analysis, [SDV] Life Sciences [q-bio], metabolic risk, Preterm infant, Dietary Supplements, Infant, Small for Gestational Age, Systematic review, Female, Cognitive function, systematic review, Food Science
Abstract: Neonatal nutritional supplements are widely used to improve growth and development but may increase risk of later metabolic disease, and effects may differ by sex. We assessed effects of supplements on later development and metabolism. We searched databases and clinical trials registers up to April 2019. Participant-level data from randomised trials were included if the intention was to increase macronutrient intake to improve growth or development of infants born preterm or small-for-gestational-age. Co-primary outcomes were cognitive impairment and metabolic risk. Supplementation did not alter cognitive impairment in toddlers (13 trials, n = 1410; adjusted relative risk (aRR) 0.88 [95% CI 0.68, 1.13]; p = 0.31) or older ages, nor alter metabolic risk beyond 3 years (5 trials, n = 438; aRR 0.94 [0.76, 1.17]; p = 0.59). However, supplementation reduced motor impairment in toddlers (13 trials, n = 1406; aRR 0.76 [0.60, 0.97]; p = 0.03), and improved motor scores overall (13 trials, n = 1406; adjusted mean difference 1.57 [0.14, 2.99]; p = 0.03) and in girls not boys (p = 0.03 for interaction). Supplementation lowered triglyceride concentrations but did not affect other metabolic outcomes (high-density and low-density lipoproteins, cholesterol, fasting glucose, blood pressure, body mass index). Macronutrient supplementation for infants born small may not alter later cognitive function or metabolic risk, but may improve early motor function, especially for girls.
Published: 2021
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18. Impaired hippocampal neurogenesis in vitro is modulated by dietary-related endogenous factors and associated with depression in a longitudinal ageing cohort study

Author: Andrea Du Preez, Sophie Lefèvre-Arbogast, Raúl González-Domínguez, Vikki Houghton, Chiara de Lucia, Dorrain Y. Low, Catherine Helmer, Catherine Féart, Cécile Delcourt, Cécile Proust-Lima, Mercè Pallàs, Alex Sánchez-Pla, Mireia Urpi-Sardà, Silvie R. Ruigrok, Barbara Altendorfer, Ludwig Aigner, Paul J. Lucassen, Aniko Korosi, Claudine Manach, Cristina Andres-Lacueva, Cécilia Samieri, Sandrine Thuret, King‘s College London, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), University of Barcelona, Instituto de Salud Carlos III [Madrid] (ISC), University of Amsterdam [Amsterdam] (UvA), Technische Universität Dresden = Dresden University of Technology (TU Dresden), Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Université de Bordeaux, Fondation pour la Recherche Médicale, Mutuelle Générale de l'Education Nationale, Conseil Régional Aquitaine, Conseil régional de Bourgogne-Franche-Comté, Fondation de France, Fondation Plan Alzheimer, Caisse nationale de solidarité pour l'autonomie, ANR-17-EURE-0019,DPH,University of Bordeaux Graduate School in Digital Public Health(2017), ANR-06-PNRA-0005,COGINUT,COGINUT : Cognition, anti-oxydants, acides gras: approche interdisciplinaire du rôle de la nutrition dans le vieillissement du cerveau(2006), Admin, Oskar, University of Bordeaux Graduate School in Digital Public Health - - DPH2017 - ANR-17-EURE-0019 - EURE - VALID, Programme National de Recherches en Alimentation et Nutrition Humaine (PNRA) - COGINUT : Cognition, anti-oxydants, acides gras: approche interdisciplinaire du rôle de la nutrition dans le vieillissement du cerveau - - COGINUT2006 - ANR-06-PNRA-0005 - PNRA - VALID, and Structural and Functional Plasticity of the nervous system (SILS, FNWI)
Subjects: Aging, Depression, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Neurogenesis, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Hippocampus, Diet, Cohort Studies, Cellular and Molecular Neuroscience, Psychiatry and Mental health, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Molecular Biology, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: Environmental factors like diet have been linked to depression and/or relapse risk in later life. This could be partially driven by the food metabolome, which communicates with the brain via the circulatory system and interacts with hippocampal neurogenesis (HN), a form of brain plasticity implicated in depression aetiology. Despite the associations between HN, diet and depression, human data further substantiating this hypothesis are largely missing. Here, we used an in vitro model of HN to test the effects of serum samples from a longitudinal ageing cohort of 373 participants, with or without depressive symptomology. 1% participant serum was applied to human fetal hippocampal progenitor cells, and changes in HN markers were related to the occurrence of depressive symptoms across a 12-year period. Key nutritional, metabolomic and lipidomic biomarkers (extracted from participant plasma and serum) were subsequently tested for their ability to modulate HN. In our assay, we found that reduced cell death and increased neuronal differentiation were associated with later life depressive symptomatology. Additionally, we found impairments in neuronal cell morphology in cells treated with serum from participants experiencing recurrent depressive symptoms across the 12-year period. Interestingly, we found that increased neuronal differentiation was modulated by increased serum levels of metabolite butyrylcarnitine and decreased glycerophospholipid, PC35:1(16:0/19:1), levels – both of which are closely linked to diet – all in the context of depressive symptomology. These findings potentially suggest that diet and altered HN could subsequently shape the trajectory of late-life depressive symptomology.
Published: 2021
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19. Surgical Treatment of Postinfarction Ventricular Septal Rupture

Author: Massimiliano Carrozzini, Nikolaos Bonaros, Bart Meyns, Roberto Scrofani, Giosuè Falcetta, Matteo Pozzi, Antonio Fiore, Stefano D'Alessandro, Salman Almobayedh, Giuseppe Filiberto Serraino, Matteo Matteucci, Vittoria Lodo, Matthias Thielmann, Piotr Suwalski, Carlo Fino, Nikolaos Kalampokas, Shabir Hussain Shah, Marek A. Deja, Dario Fina, Roberto Lorusso, Nawwar Al-Attar, Theodor Fischlein, Udo Boeken, Guglielmo Maria Actis Dato, Francesco Formica, Sandro Sponga, Adam Kowalówka, Fareed A Khouqeer, Carlo De Vincentiis, Giulio Massimi, Igor Vendramin, Jean-François Obadia, Thierry Folliguet, Daniele Ronco, Giovanni Troise, Federica Jiritano, Michele De Bonis, Cesare Beghi, Caterina Simon, Emmanuel Villa, Mariusz Kowalewski, Jurij M. Kalisnik, Shiho Naito, Marco Ranucci, Claudio Russo, CTC, RS: Carim - V04 Surgical intervention, MUMC+: MA Med Staf Spec CTC (9), CarMeN, laboratoire, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Universitá degli Studi dell’Insubria = University of Insubria [Varese] (Uninsubria), Central Clinical Hospital of the Ministry of the Interior & Administration [Warsaw, Poland] (2CHMIA), Ministry of the Interior and Administration [Warsaw, Poland] (MIA), Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Università degli studi di Parma = University of Parma (UNIPR), Università degli Studi 'Magna Graecia' di Catanzaro = University of Catanzaro (UMG), Università degli Studi di Milano, IRCCS Policlinico San Donato, CHU Henri Mondor, Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Niguarda Hospital [Milan, Italy], Università degli Studi di Udine - University of Udine [Italie], University of Pisa - Università di Pisa, Klinikum Nürnberg Nord, Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Fondazione Poliambulanza, Mauriziano Umberto Hospital [Turin, Italy] (MUH), King Fahad Medical City [Riyadh, Saudi Arabia], Luigi Sacco University Hospital [Milan], Medical University of Silesia (SUM), Upper Silesian Medical Centre [Katowice, Poland] (USMC), West German Heart Center, Universität Duisburg-Essen [Essen], University Hospitals Leuven [Leuven], King Faisal Specialist Hospital and Resarch Centre [Riyadh, Saudi Arabia] (KFSHRC), Golden Jubilee National Hospital, Glasgow, Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University Hospital Düsseldorf, Hospital Papa Giovanni XXIII (Hosp P Giovanni XXIII), University Heart Center [Hamburg], Cardiovascular Research Institute Maastricht (CARIM), Università degli Studi di Brescia = University of Brescia (UniBs), Services de Pneumologie, Exploration Fonctionnelle Respiratoire et Cardiologie (Hôpital Louis Pradel), Ronco, D., Matteucci, M., Kowalewski, M., De Bonis, M., Formica, F., Jiritano, F., Fina, D., Folliguet, T., Bonaros, N., Russo, C. F., Sponga, S., Vendramin, I., De Vincentiis, C., Ranucci, M., Suwalski, P., Falcetta, G., Fischlein, T., Troise, G., Villa, E., Dato, G. A., Carrozzini, M., Serraino, G. F., Shah, S. H., Scrofani, R., Fiore, A., Kalisnik, J. M., D'Alessandro, S., Lodo, V., Kowalowka, A. R., Deja, M. A., Almobayedh, S., Massimi, G., Thielmann, M., Meyns, B., Khouqeer, F. A., Al-Attar, N., Pozzi, M., Obadia, J. -F., Boeken, U., Kalampokas, N., Fino, C., Simon, C., Naito, S., Beghi, C., and Lorusso, R.
Subjects: Male, MORTALITY-RATES, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Medizin, Myocardial Infarction, Cohort Studies, Odds Ratio, Myocardial infarction, Prospective Studies, Coronary Artery Bypass, Prospective cohort study, Original Investigation, Ventricular Septal Rupture, OUTCOMES, Cardiogenic shock, Mortality rate, CARDIAC RUPTURE, General Medicine, MECHANICAL CIRCULATORY SUPPORT, Middle Aged, [SDV] Life Sciences [q-bio], Online Only, Female, Life Sciences & Biomedicine, Cohort study, medicine.medical_specialty, Preoperative care, EXTRACORPOREAL MEMBRANE-OXYGENATION, Medicine, General & Internal, General & Internal Medicine, medicine, Extracorporeal membrane oxygenation, Humans, cardiovascular diseases, Aged, Retrospective Studies, REPAIR, Science & Technology, business.industry, Research, ELEVATION MYOCARDIAL-INFARCTION, Perioperative, medicine.disease, Surgery, DEFECT, RISK-FACTORS, business, TASK-FORCE
Abstract: Key Points Question What are the early outcomes of surgical treatment of postinfarction ventricular septal rupture? Findings In this cohort study of 475 patients from 26 different centers worldwide, the early mortality rate for surgically treated ventricular septal rupture was 40.4%, mostly due to low cardiac output, and it did not improve in the last 2 decades. Meaning The findings of this study suggest that patient-tailored preoperative and perioperative management of postinfarction ventricular septal rupture should be addressed to improve the current suboptimal survival rates., This cohort study assesses the clinical characteristics and early outcomes for patients who received surgery for postinfarction ventricular septal rupture and identifies factors independently associated with mortality., Importance Ventricular septal rupture (VSR) is a rare but life-threatening mechanical complication of acute myocardial infarction associated with high mortality despite prompt treatment. Surgery represents the standard of care; however, only small single-center series or national registries are usually available in literature, whereas international multicenter investigations have been poorly carried out, therefore limiting the evidence on this topic. Objectives To assess the clinical characteristics and early outcomes for patients who received surgery for postinfarction VSR and to identify factors independently associated with mortality. Design, Setting, and Participants The Mechanical Complications of Acute Myocardial Infarction: an International Multicenter Cohort (CAUTION) Study is a retrospective multicenter international cohort study that includes patients who were treated surgically for mechanical complications of acute myocardial infarction. The study was conducted from January 2001 to December 2019 at 26 different centers worldwide among 475 consecutive patients who underwent surgery for postinfarction VSR. Exposures Surgical treatment of postinfarction VSR, independent of the technique, alone or combined with other procedures (eg, coronary artery bypass grafting). Main Outcomes and Measures The primary outcome was early mortality; secondary outcomes were postoperative complications. Results Of the 475 patients included in the study, 290 (61.1%) were men, with a mean (SD) age of 68.5 (10.1) years. Cardiogenic shock was present in 213 patients (44.8%). Emergent or salvage surgery was performed in 212 cases (44.6%). The early mortality rate was 40.4% (192 patients), and it did not improve during the nearly 20 years considered for the study (median [IQR] yearly mortality, 41.7% [32.6%-50.0%]). Low cardiac output syndrome and multiorgan failure were the most common causes of death (low cardiac output syndrome, 70 [36.5%]; multiorgan failure, 53 [27.6%]). Recurrent VSR occurred in 59 participants (12.4%) but was not associated with mortality. Cardiogenic shock (survived: 95 [33.6%]; died, 118 [61.5%]; P
Published: 2021
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20. Management and outcomes in critically ill nonagenarian versus octogenarian patients

Author: Bruno, Raphael Romano, Wernly, Bernhard, Kelm, Malte, Boumendil, Ariane, Morandi, Alessandro, Andersen, Finn H., Artigas, Antonio, Finazzi, Stefano, Cecconi, Maurizio, Christensen, Steffen, Faraldi, Loredana, Lichtenauer, Michael, Muessig, Johanna M., Marsh, Brian, Moreno, Rui, Oeyen, Sandra, Öhman, Christina Agvald, Pinto, Bernardo Bollen, Soliman, Ivo W., Szczeklik, Wojciech, Valentin, Andreas, Watson, Ximena, Leaver, Susannah, Boulanger, Carole, Walther, Sten, Schefold, Joerg C., Joannidis, Michael, Nalapko, Yuriy, Elhadi, Muhammed, Fjølner, Jesper, Zafeiridis, Tilemachos, De Lange, Dylan W., Guidet, Bertrand, Flaatten, Hans, Jung, Christian, Eller, Philipp, Helbok, Raimund, Schmutz, René, Nollet, Joke, de Neve, Nikolaas, Buysscher, Pieter De, Swinnen, Walter, Mikačić, Marijana, Bastiansen, Anders, Husted, Andreas, Dahle, Bård E.S., Cramer, Christine, Sølling, Christoffer, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Karolinska Institutet [Stockholm], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), the Handmaids of Charity Nursing Home / Casa di Cura Ancelle della Carità [Cremona, Italia], NTNU [Ålesund], Hospital Universitari Parc Taulí [Sabadell, Spain] (HUPT), CIBER de Epidemiología y Salud Pública (CIBERESP), RCCS–Istituto di Ricerche Farmacologiche 'Mario Negri [Bergamo, Italy], Clinical Research Center for Rare Diseases 'Aldo e Cele Daccò' [Bergamo, Italy], Humanitas University [Milan] (Hunimed), Aarhus University Hospital, ASST Great Metropolitan Niguarda / ASST Grande Ospedale Metropolitano Niguarda [Milan, Italia], Mater Misericordiae University Hospital (The Mater Hospital), NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Ghent University Hospital, Karolinska University Hospital [Stockholm], Geneva University Hospitals and Geneva University, Utrecht University [Utrecht], Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Cardinal Schwarzenberg Hospital [Pongau, Austria] (CSH), St George’s University Hospitals, Royal Devon and Exeter NHS Foundation Trust [UK], Linköping university hospital, University of Bern, Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), European Wellness International [Luhansk, Ukraine] (EWI), Alkhums Hospital [Tripoli, Libya] (AH), University Hospital of Larissa, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), University of Bergen (UiB), Haukeland University Hospital, VIP2 study group: Michael Joannidis, Philipp Eller, Raimund Helbok, René Schmutz, Joke Nollet, Nikolaas de Neve, Pieter De Buysscher, Sandra Oeyen, Walter Swinnen, Marijana Mikačić, Anders Bastiansen, Andreas Husted, Bård E S Dahle, Christine Cramer, Christoffer Sølling, Dorthe Ørsnes, Jakob Edelberg Thomsen, Jonas Juul Pedersen, Mathilde Hummelmose Enevoldsen, Thomas Elkmann, Agnieszka Kubisz-Pudelko, Alan Pope, Amy Collins, Ashok S Raj, Carole Boulanger, Christian Frey, Ciaran Hart, Clare Bolger, Dominic Spray, Georgina Randell, Helder Filipe, Ingeborg D Welters, Irina Grecu, Jane Evans, Jason Cupitt, Jenny Lord, Jeremy Henning, Joanne Jones, Jonathan Ball, Julie North, Kiran Salaunkey, Laura Ortiz-Ruiz De Gordoa, Louise Bell, Madhu Balasubramaniam, Marcela Vizcaychipi, Maria Faulkner, Mc Donald Mupudzi, Megan Lea-Hagerty, Michael Reay, Michael Spivey, Nicholas Love, Nick Spittle Nick Spittle, Nigel White, Patricia Williams, Patrick Morgan, Phillipa Wakefield, Rachel Savine, Reni Jacob, Richard Innes, Ritoo Kapoor, Sally Humphreys, Steve Rose, Susan Dowling, Susannah Leaver, Tarkeshwari Mane, Tom Lawton, Vongayi Ogbeide, Waqas Khaliq, Yolanda Baird, Antoine Romen, Arnaud Galbois, Bertrand Guidet, Christophe Vinsonneau, Cyril Charron, Didier Thevenin, Emmanuel Guerot, Guillaume Besch, Guillaume Savary, Hervé Mentec, Jean-Luc Chagnon, Jean-Philippe Rigaud, Jean-Pierre Quenot, Jeremy Castanera, Jérémy Rosman, Julien Maizel, Kelly Tiercelet, Lucie Vettoretti, Maud Mousset Hovaere, Messika Messika, Michel Djibré, Nathalie Rolin, Philippe Burtin, Pierre Garcon, Saad Nseir, Xavier Valette, Christian Rabe, Eberhard Barth, Henning Ebelt, Kristina Fuest, Marcus Franz, Michael Horacek, Michael Schuster, Patrick Meybohm, Raphael Romano Bruno, Sebastian Allgäuer, Simon Dubler, Stefan J Schaller, Stefan Schering, Stephan Steiner, Thorben Dieck, Tim Rahmel, Tobias Graf, Anastasia Koutsikou, Aristeidis Vakalos, Bogdan Raitsiou, Elli Niki Flioni, Evangelia Neou, Fotios Tsimpoukas, Georgios Papathanakos, Giorgos Marinakis, Ioannis Koutsodimitropoulos, Kounougeri Aikaterini, Nikoletta Rovina, Stylliani Kourelea, Polychronis Tasioudis, Vasiiios Zidianakis, Vryza Konstantinia, Zoi Aidoni, Brian Marsh, Catherine Motherway, Chris Read, Ignacio Martin-Loeches, Andrea Neville Cracchiolo, Aristide Morigi, Italo Calamai, Stefania Brusa, Ahmed Elhadi, Ahmed Tarek, Ala Khaled, Hazem Ahmed, Wesal Ali Belkhair, Alexander D Cornet, Diederik Gommers, Dylan W De Lange, Eva van Boven, Jasper Haringman, Lenneke Haas, Lettie van den Berg, Oscar Hoiting, Peter de Jager, Rik T Gerritsen, Tom Dormans, Willem Dieperink, Alena Breidablik Alena Breidablik, Anita Slapgard, Anne-Karin Rime, Bente Jannestad, Britt Sjøbøe, Eva Rice, Finn H Andersen, Hans Frank Strietzel, Jan Peter Jensen, Jørund Langørgen, Kirsti Tøien, Kristian Strand, Michael Hahn, Pål Klepstad, Aleksandra Biernacka, Anna Kluzik, Bartosz Kudlinski, Dariusz Maciejewski, Dorota Studzińska, Hubert Hymczak, Jan Stefaniak, Joanna Solek-Pastuszka, Joanna Zorska, Katarzyna Cwyl, Lukasz J Krzych, Maciej Zukowski, Małgorzata Lipińska-Gediga, Marek Pietruszko, Mariusz Piechota, Marta Serwa, Miroslaw Czuczwar, Mirosław Ziętkiewicz, Natalia Kozera, Paweł Nasiłowski, Paweł Sendur, Paweł Zatorski, Piotr Galkin, Ryszard Gawda, Urszula Kościuczuk, Waldemar Cyrankiewicz, Wojciech Gola, Alexandre Fernandes Pinto, Ana Margarida Fernandes, Ana Rita Santos, Cristina Sousa, Inês Barros, Isabel Amorim Ferreira, Jacobo Bacariza Blanco, João Teles Carvalho, Jose Maia, Nuno Candeias, Nuno Catorze, Vladislav Belskiy, Africa Lores, Angela Prado Mira, Catia Cilloniz, David Perez-Torres, Emilio Maseda, Enver Rodriguez, Estefania Prol-Silva, Gaspar Eixarch, Gemma Gomà, Gerardo Aguilar, Gonzalo Navarro Velasco, Marián Irazábal Jaimes, Mercedes Ibarz Villamayor, Noemí Llamas Fernández, Patricia Jimeno Cubero, Sonia López-Cuenca, Teresa Tomasa, Anders Sjöqvist, Camilla Brorsson, Fredrik Schiöler, Henrik Westberg, Jessica Nauska, Joakim Sivik, Johan Berkius, Karin Kleiven Thiringer, Lina De Geer, Sten Walther, Filippo Boroli, Joerg C Schefold, Leila Hergafi, Philippe Eckert, Ismail Yıldız, Ihor Yovenko, Yuriy Nalapko, Richard Pugh, Malbec, Odile, Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), Mater Misericordiae University Hospital [Dublin] (The Mater Hospital), Jagiellonian University Medical College / Uniwersytet Jagielloński Collegium Medicum [Krakow, Poland], Innsbruck Medical University [Austria] (IMU), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM), and Intensive Care
Subjects: Aged, 80 and over, Octogenarians, Critical Care, Frailty, Omvårdnad, Research, Critical Illness, [SDV]Life Sciences [q-bio], 610 Medicine & health, Nursing, Cohort Studies, Hospitalization, [SDV] Life Sciences [q-bio], Critical Illness/therapy, Nonagenarians, Humans, Intensive care medicine, Geriatrics and Gerontology, Outcome
Abstract: Funding Information: This study was endorsed by the ESICM. Free support for running the electronic database and was granted from the dep. of Epidemiology, University of Aarhus, Denmark. Financial support for creation of the e-CRF and maintenance of the database was possible from a grant (open project support) by Western Health region in Norway) 2018 who also funded the participating Norwegian ICUs. DRC Ile de France and URC Est helped conducting VIP2 in France. Open Access funding enabled and organized by Projekt DEAL. Publisher Copyright: © 2021, The Author(s). Background: Intensive care unit (ICU) patients age 90 years or older represent a growing subgroup and place a huge financial burden on health care resources despite the benefit being unclear. This leads to ethical problems. The present investigation assessed the differences in outcome between nonagenarian and octogenarian ICU patients. Methods: We included 7900 acutely admitted older critically ill patients from two large, multinational studies. The primary outcome was 30-day-mortality, and the secondary outcome was ICU-mortality. Baseline characteristics consisted of frailty assessed by the Clinical Frailty Scale (CFS), ICU-management, and outcomes were compared between octogenarian (80–89.9 years) and nonagenarian (> 90 years) patients. We used multilevel logistic regression to evaluate differences between octogenarians and nonagenarians. Results: The nonagenarians were 10% of the entire cohort. They experienced a higher percentage of frailty (58% vs 42%; p < 0.001), but lower SOFA scores at admission (6 + 5 vs. 7 + 6; p < 0.001). ICU-management strategies were different. Octogenarians required higher rates of organ support and nonagenarians received higher rates of life-sustaining treatment limitations (40% vs. 33%; p < 0.001). ICU mortality was comparable (27% vs. 27%; p = 0.973) but a higher 30-day-mortality (45% vs. 40%; p = 0.029) was seen in the nonagenarians. After multivariable adjustment nonagenarians had no significantly increased risk for 30-day-mortality (aOR 1.25 (95% CI 0.90–1.74; p = 0.19)). Conclusion: After adjustment for confounders, nonagenarians demonstrated no higher 30-day mortality than octogenarian patients. In this study, being age 90 years or more is no particular risk factor for an adverse outcome. This should be considered– together with illness severity and pre-existing functional capacity - to effectively guide triage decisions. Trial registration: NCT03134807 and NCT03370692. publishersversion published
Published: 2021
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21. Steroid use in elderly critically ill COVID-19 patients

Author: Wojciech Szczeklik, Hans Flaatten, Michael Joannidis, Mirosław Czuczwar, Christian Jung, Michael Beil, Raphael Romano Bruno, Jesper Fjølner, Tilemachos Zafeiridis, Rui Moreno, Sviri Sigal, Bernardo Bollen Pinto, Bernhard Wernly, Peter Vernon van Heerden, Muhammed Elhadi, Antonio Artigas, David M. Dudzinski, Georg Wolff, Susannah Leaver, Finn H. Andersen, Brian Marsh, Sandra Oeyen, Dylan W. de Lange, Malte Kelm, Joerg C. Schefold, Ariane Boumendil, Maurizio Cecconi, Bertrand Guidet, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Aarhus University Hospital, Massachusetts General Hospital [Boston], Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), Geneva University Hospitals and Geneva University, University of Bern, The Hebrew University of Jerusalem (HUJ), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Medical University of Lublin, University of Tripoli - University Al Fateh, Innsbruck Medical University [Austria] (IMU), Ghent University Hospital, University Hospital of Larissa, Mater Misericordiae University Hospital [Dublin] (The Mater Hospital), Aalesund University College, Norwegian University of Science and Technology [Trondheim] (NTNU), Norwegian University of Science and Technology (NTNU), NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Humanitas University [Milan] (Hunimed), St George’s University Hospitals, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Réanimation Médicale [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Utrecht University [Utrecht], University of Bergen (UiB), Haukeland University Hospital, NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM), HAL-SU, Gestionnaire, Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Mater Misericordiae University Hospital (The Mater Hospital), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), viruses, Critical Illness, MEDLINE, 610 Medicine & health, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, MESH: Risk Factors, Secondary analysis, Medicine and Health Sciences, medicine, Research Letter, Humans, MESH: COVID-19, MESH: SARS-CoV-2, 030212 general & internal medicine, Intensive care medicine, skin and connective tissue diseases, ComputingMilieux_MISCELLANEOUS, Aged, MESH: Aged, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, MESH: Humans, business.industry, Critically ill, SARS-CoV-2, fungi, COVID-19, MESH: Steroids, 3. Good health, respiratory tract diseases, body regions, 030228 respiratory system, Steroid use, MESH: Critical Illness, Steroids, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: More than a year after the onset of the SARS-Cov-2 pandemic, treating patients with COVID-19 remains a challenge. By contrast to the rapid development of effective vaccines against SARS-Cov-2, the development of specific and effective therapeutics against COVID-19 remains largely unresolved., This secondary analysis of the COVIP study shows a higher 30-day-mortality in critically ill elderly COVID-19 patients who received steroids as part of their treatment.
Published: 2021
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22. Respective roles of non-pharmaceutical interventions in bronchiolitis outbreaks: an interrupted time-series analysis based on a multinational surveillance system

Author: Lea, Lenglart, Naim, Ouldali, Kate, Honeyford, Zsolt, Bognar, Silvia, Bressan, Danilo, Buonsenso, Liviana, Da Dalt, Tisham, De, Ruth, Farrugia, Ian K, Maconochie, Henriette A, Moll, Rianne, Oostenbrink, Niccolo, Parri, Damian, Roland, Katy, Rose, Esra, Akyüz Özkan, François, Angoulvant, Camille, Aupiais, Clarissa, Barber, Michael, Barrett, Romain, Basmaci, Susana, Castanhinha, Antonio, Chiaretti, Sheena, Durnin, Patrick, Fitzpatrick, Laszlo, Fodor, Borja, Gomez, Susanne, Greber-Platzer, Romain, Guedj, Florian, Hey, Lina, Jankauskaite, Daniela, Kohlfuerst, Ines, Mascarenhas, Anna Maria, Musolino, Zanda, Pučuka, Sofia, Reis, Alexis, Rybak, Petra, Salamon, Matthias, Schaffert, Keren, Shahar-Nissan, Maria Chiara, Supino, Ozlem, Teksam, Caner, Turan, Roberto, Velasco, Ruud G, Nijman, Luigi, Titomanlio, Vanda, Anacleto, Orkun, Aydin, Elena, Bellelli, Ron, Berant, Thibault, De Groc, Sara, Geitoeira, Florian, Hoffmann, Franziska, Leeb, Fiona, Leonard, Mark, Lyttle, Lia, Mano, Vytenis, Masillonis, Rosa, Morello, Francisa, Saraiva, Gabor, Simon, Ines Silva, Costa, Joao Sous, Marques, Jonas, Thüminger, Corinne, Vasilico, Anna Chiara, Vittucci, Christoph, Zurl, Pediatrics, Business Economics, Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Sainte Justine [Montréal], Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Association Clinique et Thérapeutique Infantile du Val de Marne (ACTIV), The institute of cancer research [London], Pál Heim Children's Hospital = Heim Pál Gyermekkórház [Budapest], Azienda Ospedale Università di Padova = Hospital-University of Padua (AOUP), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Imperial College London, Mater Dei Hospital [Malta], St Mary's Hospital [London], Hammersmith Hospital NHS Imperial College Healthcare, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Azienda Ospedaliero Universitaria A. Meyer [Firenze, Italy], University of Leicester, University Hospitals Leicester, Ondokuz Mayis University (OMU), Université Paris Cité (UPCité), AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Jean Verdier [AP-HP], North Bristol NHS Trust [Bristol, UK], Children's Health Ireland [Crumlin, Dublin, Ireland] (CHI), University College Dublin [Dublin] (UCD), Hôpital Louis Mourier - AP-HP [Colombes], Centro Hospitalar de Lisboa Central E.P.E, CHI at Tallaght Children's Outpatient and Emergency Care Unit [Tallaght, Ireland] (COECU), CHI at Temple Street [Temple Street, Ireland] (TS), Fejér County Szent György University Teaching Hospital [Szekesfehervar, Hungary] (FCSGUTH), Hospital Universitario Cruces = Cruces University Hospital, Medizinische Universität Wien = Medical University of Vienna, Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Dr von Hauner Children's Hospital [Munich, Germany], Ludwig-Maximilians-Universität München (LMU), Ludwig-Maximilians University [Munich] (LMU), Hospital of Lithuanian University of Health Sciences Kauno Klinikos [Kaunas, Lithuania], Medical University of Graz, Hospital Prof Doutor Fernando Fonseca [Amadora, Portugal], Bambino Gesù Children’s Hospital [Rome, Italy], Children's Clinical University Hospital [Riga, Latvia] (CCUH), Centro Hospitalar Tondela-Viseu [Viseu, Portugal] (CHTV), Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Schneider Children’s Medical Center [Petah Tikva, Israel] (SCMC), Hacettepe University = Hacettepe Üniversitesi, Mersin University, Rio Hortega University Hospital (Hospital Universitario Río Hortega) [Valladolid, Spain] (RHUH), Maladies neurodéveloppementales et neurovasculaires (NeuroDiderot (UMR_S_1141 / U1141)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), EPISODES Study Group., and Angoulvant, François
Subjects: [SDV] Life Sciences [q-bio], Pulmonary and Respiratory Medicine, SDG 3 - Good Health and Well-being, [SDV]Life Sciences [q-bio]
Abstract: BackgroundBronchiolitis is a major source of morbimortality among young children worldwide. Non-pharmaceutical interventions (NPIs) implemented to reduce the spread of severe acute respiratory syndrome coronavirus 2 may have had an important impact on bronchiolitis outbreaks, as well as major societal consequences. Discriminating between their respective impacts would help define optimal public health strategies against bronchiolitis. We aimed to assess the respective impact of each NPI on bronchiolitis outbreaks in 14 European countries.MethodsWe conducted a quasi-experimental interrupted time-series analysis based on a multicentre international study. All children diagnosed with bronchiolitis presenting to the paediatric emergency department of one of 27 centres from January 2018 to March 2021 were included. We assessed the association between each NPI and change in the bronchiolitis trend over time by seasonally adjusted multivariable quasi-Poisson regression modelling.ResultsIn total, 42 916 children were included. We observed an overall cumulative 78% (95% CI −100– −54%; pConclusionsSeveral NPIs were associated with a reduction of bronchiolitis outbreaks, including full lockdown, school closure, teleworking and facial masking. Some of these public health interventions may be considered to further reduce the global burden of bronchiolitis.
Published: 2022
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23. 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
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24. ICU-Mortality in Old and Very Old Patients Suffering From Sepsis and Septic Shock

Author: Raphael Romano Bruno, Bernhard Wernly, Behrooz Mamandipoor, Richard Rezar, Stephan Binnebössel, Philipp Heinrich Baldia, Georg Wolff, Malte Kelm, Bertrand Guidet, Dylan W. De Lange, Daniel Dankl, Andreas Koköfer, Thomas Danninger, Wojciech Szczeklik, Sviri Sigal, Peter Vernon van Heerden, Michael Beil, Jesper Fjølner, Susannah Leaver, Hans Flaatten, Venet Osmani, Christian Jung, HAL-SU, Gestionnaire, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Fondazione Bruno Kessler [Trento, Italy] (FBK), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Réanimation Médicale [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), University Medical Center [Utrecht], Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Hadassah Hebrew University Medical Center [Jerusalem], Aarhus University Hospital, St George’s University Hospitals, Haukeland University Hospital, University of Bergen (UiB), and Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Medicine (General), obesity, medicine.medical_specialty, critically ill, geriatric, Logistic regression, sepsis, Sepsis, 03 medical and health sciences, R5-920, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, very old, Intensive care, Internal medicine, medicine, Clinical significance, 030212 general & internal medicine, old, Original Research, intensive care, octogenarian, Old patients, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Icu mortality, business.industry, Septic shock, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, 030208 emergency & critical care medicine, General Medicine, medicine.disease, Obesity, 3. Good health, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: Purpose: Old (>64 years) and very old (>79 years) intensive care patients with sepsis have a high mortality. In the very old, the value of critical care has been questioned. We aimed to compare the mortality, rates of organ support, and the length of stay in old vs. very old patients with sepsis and septic shock in intensive care.Methods: This analysis included 9,385 patients, from the multi-center eICU Collaborative Research Database, with sepsis; 6184 were old (aged 65–79 years), and 3,201 were very old patients (aged 80 years and older). A multi-level logistic regression analysis was used to fit three sequential regression models for the binary primary outcome of ICU mortality. A sensitivity analysis in septic shock patients (n = 1054) was also conducted.Results: In the very old patients, the median length of stay was shorter (50 ± 67 vs. 56 ± 72 h; p < 0.001), and the rate of a prolonged ICU stay was lower (>168 h; 9 vs. 12%; p < 0.001) than the old patients. The mortality from sepsis was higher in very old patients (13 vs. 11%; p = 0.005), and after multi-variable adjustment being very old was associated with higher odds for ICU mortality (aOR 1.32, 95% CI 1.09–1.59; p = 0.004). In patients with septic shock, mortality was also higher in the very old patients (38 vs. 36%; aOR 1.50, 95% CI 1.10–2.06; p = 0.01).Conclusion: Very old ICU-patients suffer from a slightly higher ICU mortality compared with old ICU-patients. However, despite the statistically significant differences in mortality, the clinical relevance of such minor differences seems to be negligible.
Published: 2021
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25. CD4/CD8 Ratio and the Risk of Kaposi Sarcoma or Non-Hodgkin Lymphoma in the Context of Efficiently Treated Human Immunodeficiency Virus (HIV) Infection: A Collaborative Analysis of 20 European Cohort Studies

Author: Caby, F., Guiguet, M., Weiss, L., Winston, A. d., Miro, J. M., Konopnicki, D., Le Moing, V., Bonnet, F. h., Reiss, P., Mussini, C., Poizot-Martin, I., Taylor, N. l., Skoutelis, A., Meyer, L., Goujard, C., Bartmeyer, B., Boesecke, C., Antinori, A., Quiros-Roldan, E., Wittkop, L., Frederiksen, C., Castagna, A., Thurnheer, M. C., Svedhem, V., Jose, S., Costagliola, D., Mary-Krause, M., Grabar, S., Judd, A., Zangerle, R., Touloumi, G., Warszawski, J., Dabis, F., Krause, M. M., Ghosn, J., Leport, C., Wit, F., Prins, M., Bucher, H., Gibb, D., Fätkenheuer, G., Del Amo, J., Obel, N., Thorne, C., Mocroft, A., Kirk, O., Stephan, C., Pérez-Hoyos, S., Hamouda, O., Chkhartishvili, N., Noguera-Julian, A., Monforte, A. D., Brockmeyer, N., Prieto, L., Conejo, P. R., Soriano-Arandes, A., Battegay, M., Kouyos, R., Casabona, J., Miró, J. M., Konopnick, D., Goetghebuer, T., Sönnerborg, A., Torti, C., Sabin, C., Teira, R., Garrido, M., Haerry, D., Statistics In System biology and Translational Medicine (SISTM), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)- Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Victor Dupouy, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imperial College London, University of Barcelona, Université libre de Bruxelles (ULB), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], University of Amsterdam [Amsterdam] (UvA), Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), 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 Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Evangelismos Athens General Hospital, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hôpital Bicêtre, Robert Koch Institute [Berlin] (RKI), University Hospital Bonn, National Institute for Infectious Diseases 'Lazzaro Spallanzani', Università degli Studi di Brescia = University of Brescia (UniBs), Team MORPH3EUS (INSERM U1219 - UB - ISPED), University of Copenhagen = Københavns Universitet (UCPH), IRCCS Ospedale San Raffaele [Milan, Italy], Bern University Hospital [Berne] (Inselspital), Karolinska Institutet [Stockholm], Public Health England [London], Hôpital Cochin [AP-HP], Agence Nationale de Recherches sur le Sida et les Hépatites Virales, (CD4/CD8 ratio and cancer risk) project Working Group for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in EuroCoord: Ali Judd, Robert Zangerle, Giota Touloumi, Josiane Warszawski, Laurence Meyer, François Dabis, Murielle Mary Krause, Jade Ghosn, Catherine Leport, Linda Wittkop, Peter Reiss, Ferdinand Wit, Maria Prins, Heiner Bucher, Diana Gibb, Gerd Fätkenheuer, Julia Del Amo, Niels Obel, Claire Thorne, Amanda Mocroft, Ole Kirk, Christoph Stephan, Santiago Pérez-Hoyos, Osamah Hamouda, Barbara Bartmeyer, Nikoloz Chkhartishvili, Antoni Noguera-Julian, Andrea Antinori, Antonella d'Arminio Monforte, Norbert Brockmeyer, Luis Prieto, Pablo Rojo Conejo, Antoni Soriano-Arandes, Manuel Battegay, Roger Kouyos, Cristina Mussini, Jordi Casabona, Jose M Miró, Antonella Castagna, Deborah Konopnick, Tessa Goetghebuer, Anders Sönnerborg, Carlo Torti, Caroline Sabin, Ramon Teira, Myriam Garrido, David Haerry, European Project: 287519, European Project: 260694,EC:FP7:HEALTH,FP7-HEALTH-2010-single-stage,EUROCOORD(2011), Admin, Oskar, European Union Seventh Framework Programme - 287519 - INCOMING, European Network of HIV/AIDS Cohort Studies to Coordinate at European and International Level Clinical Research on HIV/AIDS - EUROCOORD - - EC:FP7:HEALTH2011-01-01 - 2015-12-31 - 260694 - VALID, Caby, Fabienne, Guiguet, Marguerite, Weiss, Laurence, Winston, Alan, Miro, Jose M, Konopnicki, Deborah, Le Moing, Vincent, Bonnet, Fabrice, Reiss, Peter, Mussini, Cristina, Poizot-Martin, Isabelle, Taylor, Ninon, Skoutelis, Athanasio, Meyer, Laurence, Goujard, Cécile, Bartmeyer, Barbara, Boesecke, Christoph, Antinori, Andrea, Quiros-Roldan, Eugenia, Wittkop, Linda, Frederiksen, Casper, Castagna, Antonella, Thurnheer, Maria Christine, Svedhem, Veronica, Jose, Sophie, Costagliola, Dominique, Mary-Krause, Murielle, Grabar, Sophie, Global Health, Infectious diseases, AII - Infectious diseases, and APH - Aging & Later Life
Subjects: CD4/CD8 ratio, CD8 T-cells, Kaposi sarcoma, efficient cART, non-Hodgkin lymphoma, 0301 basic medicine, Microbiology (medical), Lymphoma, [SDV]Life Sciences [q-bio], 030106 microbiology, CD4-CD8 Ratio, Non-Hodgkin, HIV Infections, Kaposi, Efficient cART, Drug resistance, HIV superinfection, CD8-Positive T-Lymphocytes, medicine.disease_cause, Men who have sex with men, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, CD4 Lymphocyte Count, HIV, Humans, Incidence, Risk Factors, Lymphoma, Non-Hodgkin, Sarcoma, Kaposi, immune system diseases, Medicine, 030212 general & internal medicine, Non-Hodgkin lymphoma, Transmission (medicine), business.industry, Sarcoma, Resistance mutation, 3. Good health, Infectious Diseases, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Superinfection, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Viral load, HIV drug resistance, Demography
Abstract: BackgroundA persistently low CD4/CD8 ratio has been reported to inversely correlate with the risk of non-AIDS defining cancer in people living with human immunodeficiency virus (HIV; PLWH) efficiently treated by combination antiretroviral therapy (cART). We evaluated the impact of the CD4/CD8 ratio on the risk of Kaposi sarcoma (KS) or non-Hodgkin lymphoma (NHL), still among the most frequent cancers in treated PLWH.MethodsPLWH from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) were included if they achieved virological control (viral load ≤ 500 copies/mL) within 9 months following cART and without previous KS/LNH diagnosis. Cox models were used to identify factors associated with KS or NHL risk, in all participants and those with CD4 ≥ 500/mm3 at virological control. We analyzed the CD4/CD8 ratio, CD4 count and CD8 count as time-dependent variables, using spline transformations.ResultsWe included 56 708 PLWH, enrolled between 2000 and 2014. At virological control, the median (interquartile range [IQR]) CD4 count, CD8 count, and CD4/CD8 ratio were 414 (296–552)/mm3, 936 (670–1304)/mm3, and 0.43 (0.28–0.65), respectively. Overall, 221 KS and 187 NHL were diagnosed 9 (2–37) and 18 (7–42) months after virological control. Low CD4/CD8 ratios were associated with KS risk (hazard ratio [HR] = 2.02 [95% confidence interval {CI } = 1.23–3.31]) when comparing CD4/CD8 = 0.3 to CD4/CD8 = 1) but not with NHL risk. High CD8 counts were associated with higher NHL risk (HR = 3.14 [95% CI = 1.58–6.22]) when comparing CD8 = 3000/mm3 to CD8 = 1000/mm3). Similar results with increased associations were found in PLWH with CD4 ≥ 500/mm3 at virological control (HR = 3.27 [95% CI = 1.60–6.56] for KS; HR = 5.28 [95% CI = 2.17–12.83] for NHL).ConclusionsLow CD4/CD8 ratios and high CD8 counts despite effective cART were associated with increased KS/NHL risks respectively, especially when CD4 ≥ 500/mm3.
Published: 2021
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26. New developments in the field of mastocytosis and mast cell activation syndromes: a summary of the Annual Meeting of the European Competence Network on Mastocytosis (ECNM) 2019

Author: Jason Gotlib, Karin Hartmann, Cem Akin, Michel Arock, Peter Valent, Wolfgang R. Sperr, Karl Sotlar, Lawrence B. Schwartz, Hans-Peter Horny, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Stanford Cancer Institute, Medizinische Universität Wien = Medical University of Vienna, University Hospital Basel [Basel], Virginia Commonwealth University (VCU), University of Michigan [Ann Arbor], University of Michigan System, Ludwig-Maximilians-Universität München (LMU), Arock, Michel, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), 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: Adult, tyrosine-kinase inhibitors, Cancer Research, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Hematologic Neoplasms, Disease, Article, 03 medical and health sciences, 0302 clinical medicine, Mastocytosis, Systemic, Bone Marrow, MESH: Child, Humans, Medicine, Mast Cells, Systemic mastocytosis, Child, MESH: Mastocytosis, Systemic, mastocytosis, MESH: Humans, business.industry, Mast cell activation, Network on, scoring, KIT, MESH: Adult, MESH: Mast Cells, Hematology, medicine.disease, Dermatology, 3. Good health, Europe, medicine.anatomical_structure, classification, Oncology, 030220 oncology & carcinogenesis, MESH: Mastocytosis, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Bone Marrow, MESH: Europe, Bone marrow, business, 030215 immunology
Abstract: International audience; Mastocytosis are a group of hematologic neoplasms characterized by an accumulation of atypical mast cells in one or several organs/tissues, often accompanied by mast cell activation. Whereas in children the disease manifestations are mostly limited to the skin, in adults the disease is usually systemic (systemic mastocytosis; SM) and involves the bone marrow and/or other internal organs. Several variants of SM have been defined. Whereas most patients have indolent SM, some patients have advanced SM, which underlines the complexity of SM. In 2002, a European consortium of clinicians and scientists initiated a multidisciplinary, multinational cooperative network, termed the 'European Competence Network on Mastocytosis' (ECNM), with the aim to improve diagnosis and therapy of patients with mastocytosis and other mast cell activation disorders. Since then, members of the ECNM have organized Annual Meetings in several European countries. The present article provides a summary of advances in the field presented during the 17th Annual ECNM meeting held in Salzburg in October 2019.
Published: 2019
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27. HIST1H1E heterozygous protein‐truncating variants cause a recognizable syndrome with intellectual disability and distinctive facial gestalt: A study to clarify the HIST1H1E syndrome phenotype in 30 individuals

Author: John M. Graham, Anna Ardissone, Dieter Kotzot, Paul R. Mark, Anna Zachariou, Guillermo Lay-Son, Allyn McConkie-Rosell, John Pappas, Karen Low, Fiona Stewart, Chey Loveday, Brian G. Skotko, Melissa Lees, Helen Stewart, Ho Ming Luk, Cheryl Cytrynbaum, Rachel Horton, Siddharth Banka, Gerard Marion, Deborah J. Shears, Marie T. McDonald, Ricardo A. Verdugo, Christine Coubes, Yuri A. Zarate, Christophe Phillipe, Katrina Tatton-Brown, Clare Allen, Deepika D.Cunha Burkardt, Rosanna Weksberg, I. Karen Temple, Alexia Bourgois, David J. Amor, Frédéric Tran Mau-Them, Laurence Faivre, Case Western Reserve University [Cleveland], The institute of cancer research [London], University College London Hospitals (UCLH), Murdoch Children's Research Institute (MCRI), University of Melbourne, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', University of Manchester [Manchester], Manchester University NHS Foundation Trust (MFT), Service de Génétique [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), The Hospital for sick children [Toronto] (SickKids), Hôpital d'Enfants [CHU Dijon], Hôpital du Bocage, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), University Hospital Southampton NHS Foundation Trust, Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Pontificia Universidad Católica de Chile (UC), Great Ormond Street Hospital for Children [London] (GOSH), University Hospitals Bristol, Department of Health Clinical Genetic Service Centre, Spectrum Health [Grand Rapids], Department of Molecular Genetics and Microbiology [Durham] (MGM), Duke University [Durham], New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Department of Clinical Genetics [Churchill Hospital], Churchill Hospital Oxford Centre for Haematology, Harvard Medical School [Boston] (HMS), Belfast City Hospital, Oxford University Hospitals NHS Trust, University of Oxford [Oxford], University of Southampton, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Universitad de Chile, Arkansas Children's Hospital, Cedars-Sinai Medical Center, St George’s University Hospitals, and Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Heterozygote, Bioinformatics, Corpus callosum, Rahman syndrome, Histones, 03 medical and health sciences, Frontal Bossing, 0302 clinical medicine, HIST1H1E, Gene cluster, Intellectual disability, Genetics, Humans, Learning, Medicine, Epigenetics, Genetics (clinical), 030304 developmental biology, Behavior, [SDV.GEN]Life Sciences [q-bio]/Genetics, 0303 health sciences, epigenetic regulator gene, biology, business.industry, Facies, Heterozygote advantage, Syndrome, medicine.disease, Phenotype, Histone, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, intellectual disability, Mutation, biology.protein, Growth and Development, business, 030217 neurology & neurosurgery
Abstract: International audience; Histone Gene Cluster 1 Member E, HIST1H1E, encodes Histone H1.4, is one of a family of epigenetic regulator genes, acts as a linker histone protein, and is responsible for higher order chromatin structure. HIST1H1E syndrome (also known as Rahman syndrome, OMIM #617537) is a recently described intellectual disability (ID) syndrome. Since the initial description of five unrelated individuals with three different heterozygous protein-truncating variants (PTVs) in the HIST1H1E gene in 2017, we have recruited 30 patients, all with HIST1H1E PTVs that result in the same shift in frame and that cluster to a 94-base pair region in the HIST1H1E carboxy terminal domain. The identification of 30 patients with HIST1H1E variants has allowed the clarification of the HIST1H1E syndrome phenotype. Major findings include an ID and a recognizable facial appearance. ID was reported in all patients and is most frequently of moderate severity. The facial gestalt consists of a high frontal hairline and full lower cheeks in early childhood and, in later childhood and adulthood, affected individuals have a strikingly high frontal hairline, frontal bossing, and deep-set eyes. Other associated clinical features include hypothyroidism, abnormal dentition, behavioral issues, cryptorchidism, skeletal anomalies, and cardiac anomalies. Brain magnetic resonance imaging (MRI) is frequently abnormal with a slender corpus callosum a frequent finding.
Published: 2019
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28. Does the severity of obesity influence bone density, geometry and strength in adolescents?

Author: David Thivel, Daniel Courteix, Daniel Weghuber, Grace O'Malley, Bruno Pereira, Martine Duclos, Yves Boirie, Alicia Fillon, Lore Metz, Valérie Julian, Department of Sport Medicine and Functional Explorations, CHU Clermont-Ferrand, Childhood Obesity Service, Temple Street Children's University Hospital, Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques (AME2P), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-UFR Sciences et Techniques des Activités Physiques et Sportives - Clermont-Auvergne (UFR STAPS - UCA), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Observatoire national de l’activité physique et de la sédentarité (ONAPS), Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Psychoneuroimmunologie, nutrition et génétique, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service Médecine du Sport et Explorations Fonctionnelles [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], Centre de Recherche en Nutrition Humaine Auvergne [CHU Clermont-Ferrand] (CRNH A), Université Clermont Auvergne (UCA)-UFR Sciences et Techniques des Activités Physiques et Sportives - Clermont-Auvergne (UFR STAPS - UCA), and Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA)
Subjects: musculoskeletal diseases, Percentile, trabecular bone score, Adolescent, Bone density, [SDV]Life Sciences [q-bio], 030209 endocrinology & metabolism, Geometry, body mass index, Childhood obesity, 03 medical and health sciences, 0302 clinical medicine, Trabecular bone score, Bone Density, Humans, Medicine, Obesity, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Univariate analysis, Nutrition and Dietetics, business.industry, Health Policy, musculoskeletal, neural, and ocular physiology, Public Health, Environmental and Occupational Health, medicine.disease, musculoskeletal system, Cross-Sectional Studies, Pediatrics, Perinatology and Child Health, Lean body mass, business, bone mineral density, Body mass index, childhood obesity, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Background: Relationships between the severity of obesity and bone health remain underexplored.Objectives: To compare whole-body and localized bone mineral content (BMC) and density (BMD), trabecular bone score (TBS) and hip geometry and strength between adolescents with obesity versus extreme obesity.Methods: This cross-sectional study included 154 adolescents (12-15 years, 62% females) who were classified as having obesity (OG, [95th-99th] percentile) or extreme obesity (EOG, >99th percentile). Fat mass (FM), lean mass (LM), BMC, BMD for total-body-less-head (TBLH), lumbar spine (LS), hip, TBS and geometric and strength indices at the narrow-neck (NN), femoral shaft (FS) and intertrochanteric regions (IT) were assessed by Dual-X-ray Absorptiometry (DXA).Results: There was no significant sex-interaction. For both sexes, TBLH BMC and BMD were not different between groups. TBS was lower in EOG compared with OG in both sexes in univariate analysis and after adjustment with maturation and body weight (p < 0.05). Hip BMD was significantly higher in the EOG compared to OG only after adjustment with maturation and fat mass percentage (p < 0.05 for men, p < 0.01 for women). For both sexes, TBLH, LS and hip BMC and BMD positively correlated with weight, BMI, LM and FM. TBS negatively correlated with BMI-percentile in both sexes, with a negative correlation with FM for males alone. Hip BMC and BMD, BMD, ACT and CSA at the three hip sites positively correlated with BMI-percentile in males.Conclusions: Extreme obesity impacts bone health depending on anatomical sites, altering lumbar trabecular bone in both males and females adolescents.
Published: 2021
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29. A randomized phase 3 trial of auto vs. allo transplantation as part of first-line therapy in poor-risk peripheral T-NHL

Author: Martin Wilhelm, Bettina Altmann, Mathieu Leclerc, Laurence de Leval, Ulrich Keller, Arnaud Jaccard, Emmanuel Gyan, Olivier Tournilhac, Peter Reimer, Maike Nickelsen, Martin Dreyling, Jacques-Olivier Bay, Karin Bilger, Bernd Metzner, Andreas Viardot, Laurence Sanhes, Murielle Roussel, Philippe Gaulard, Marita Ziepert, Noel Milpied, Gandhi Damaj, Norbert Schmitz, Friederike Braulke, Walter Lindemann, Eva Maria Wagner-Drouet, Alain Delmer, Bertram Glass, Guillaume Cartron, Thierry Lamy, Krimo Bouabdallah, Viola Poeschel, Frank Kroschinsky, Birte Friedrichs, Lorenz Truemper, David Sibon, Peter Dreger, Andreas Rosenwald, Christian Gisselbrecht, Mathias Haenel, Anne Banos, Gerald Wulf, University Hospital Münster - Universitaetsklinikum Muenster [Germany] (UKM), Georg-August-University [Göttingen], Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Universität Leipzig [Leipzig], Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Limoges, Kliniken Essen-Mitte, University Medical Center [Mainz], Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Centre Hospitalier Saint Jean de Perpignan, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), 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)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], University Hospital Carl Gustav Carus [Dresden, Germany], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Catholic Hospital = Katholisches Krankenhaus [Hagen], Universität Heidelberg [Heidelberg], Universitätsklinikum Ulm - University Hospital of Ulm, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), CHU Clermont-Ferrand, Helios-Klinikum Berlin-Buch, University Hospital Homburg, Institut d'Hématologie de Basse-Normandie (IHBN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, CHU Necker - Enfants Malades [AP-HP], Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Institut de Cancérologie de Strasbourg Europe (ICANS), Le CHCB, Centre Hospitalier de la Côte Basque, Hospital of Chemnitz, Klinikum der Universität [München], Klinikum Oldenburg, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Onkologie Lerchenfeld [Hamburg], CHU Estaing [Clermont-Ferrand], Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne (UCA), CIC Clermont Ferrand, Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-Centre de Pharmacologie Clinique, Georg-August-University = Georg-August-Universität Göttingen, Universität Leipzig, Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), 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 ), Julius-Maximilians-Universität Würzburg (JMU), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Universität Heidelberg [Heidelberg] = Heidelberg University, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier de la Côte Basque (CHCB), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Herrada, Anthony
Subjects: 0301 basic medicine, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Vincristine, medicine.medical_specialty, Allogeneic transplantation, Immunology, CHOP, Biochemistry, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, International Prognostic Index, Autologous stem-cell transplantation, immune system diseases, Internal medicine, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Anaplastic large-cell lymphoma, Etoposide, Lymphoid Neoplasia, business.industry, Lymphoma, T-Cell, Peripheral, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Cell Biology, Hematology, medicine.disease, 3. Good health, Transplantation, 030104 developmental biology, surgical procedures, operative, business, human activities, 030215 immunology, medicine.drug
Abstract: Standard first-line therapy for younger patients with peripheral T-cell lymphoma consists of six courses of CHOP or CHOEP consolidated by high-dose therapy and autologous stem cell transplantation (AutoSCT). We hypothesized that consolidative allogeneic transplantation (AlloSCT) could improve outcome. 104 patients with nodal peripheral T-cell lymphoma except ALK+ ALCL, 18 to 60 years of age, all stages and IPI scores except stage 1 and aaIPI 0, were randomized to receive 4 x CHOEP and 1 x DHAP followed by high-dose therapy and AutoSCT or myeloablative conditioning and AlloSCT. The primary endpoint was event-free survival (EFS) at three years. After a median follow-up of 42 months, 3-year EFS of patients undergoing AlloSCT was 43% (95% confidence interval [CI]: 29%; 57%) as compared to 38% (95% CI: 25%; 52%) after AutoSCT. Overall survival at 3 years was 57% (95% CI: 43%; 71%) versus 70% (95% CI: 57%; 82%) after AlloSCT or AutoSCT, without significant differences between treatment arms. None of 21 responding patients proceeding to AlloSCT as opposed to 13 of 36 patients (36%) proceeding to AutoSCT relapsed. Eight of 26 patients (31%) and none of 41 patients died due to transplant-related toxicity after allogeneic and autologous transplantation, respectively. In younger patients with T-cell lymphoma standard chemotherapy consolidated by autologous or allogeneic transplantation results in comparable survival. The strong graft-versus-lymphoma effect after AlloSCT was counterbalanced by transplant-related mortality. CHO(E)P followed by AutoSCT remains the preferred treatment option for transplant-eligible patients. AlloSCT is the treatment of choice for relapsing patients also after AutoSCT.
Published: 2021
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30. Athletes with valvular heart disease and competitive sports: a position statement of the Sport Cardiology Section of the European Association of Preventive Cardiology

Author: Frank van Buuren, Hanne Kruse Rasmussen, Christian Schmied, Domenico Corrado, Sanjay Sharma, Stefano Caselli, Axel Pressler, Luis Serratosa, Michael Papadakis, Alessandro Biffi, François Carré, Lothar Faber, Hein Heidbuchel, Erik Ekker Solberg, Andre La Gerche, Mats Börjesson, Nikola Bogunovic, Antonio Pelliccia, Paolo Emilio Adami, Sabiha Gati, Flavio D'Ascenzi, Volker Rudolph, Josef Niebauer, Klaus Peter Mellwig, Nicole M. Panhuyzen-Goedkoop, Ruhr-Universität Bochum [Bochum], Imperial College London, Royal Brompton Hospital, St George’s University Hospitals, Disney Research Zürich (DRZ), Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), University of Gothenburg (GU), 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), CHU Pontchaillou [Rennes], Diakonhjemmet Hospital, Antwerp University Hospital [Edegem] (UZA), Universita degli Studi di Padova, Hospital Universitario Quironsalud, Baker Heart and Diabetes Institute (AUSTRALIA), Università degli Studi di Siena = University of Siena (UNISI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Università degli Studi di Padova = University of Padua (Unipd)
Subjects: medicine.medical_specialty, Epidemiology, Population, Physical activity, Cardiology, Heart Valve Diseases, Aortic regurgitation, 030204 cardiovascular system & hematology, Recommendations, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Mitral valve prolapse, Humans, 030212 general & internal medicine, education, Association (psychology), Exercise, Mitral regurgitation, Sport, education.field_of_study, Mitral stenosis, biology, Athletes, business.industry, Aortic stenosis, valvular heart disease, Pulmonary pressure, Valvular heart disease, Sports, medicine.disease, biology.organism_classification, 3. Good health, Natural history, Preventive cardiology, cardiovascular system, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Human medicine, Cardiology and Cardiovascular Medicine, business
Abstract: This article provides an overview of the recommendations from the Sports Cardiology section of the European Association of Preventive Cardiology on sports participation in individuals with valvular heart disease (VHD). The aim of these recommendations is to encourage regular physical activity including sports participation, with reasonable precaution to ensure a high level of safety for all affected individuals. Valvular heart disease is usually an age-related degenerative process, predominantly affecting individuals in their fifth decade and onwards. However, there is an increasing group of younger individuals with valvular defects. The diagnosis of cardiac disorders during routine cardiac examination often raises questions about on-going participation in competitive sport with a high dynamic or static component and the level of permissible physical effort during recreational exercise. Although the natural history of several valvular diseases has been reported in the general population, little is known about the potential influence of chronic intensive physical activity on valve function, left ventricular remodelling pulmonary artery pressure, and risk of arrhythmia. Due to the sparsity of data on the effects of exercise on VHD, the present document is largely based on clinical experience and expert opinion.
Published: 2021
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31. Cardiometabolic efficacy of multidisciplinary weight loss interventions is not altered in adolescents with obesity initially diagnosed or with a persistent metabolic syndrome

Author: Valérie Julian, David Thivel, Yves Boirie, Ana R Damaso, Katharina Maruszczak, Piotr Matłosz, Marwa Khammassi, Frédéric Dutheil, Daniel Weghuber, Laurie Isacco, Bruno Pereira, Martine Duclos, Département d'Informatique [Jendouba] (Université de Jendouba), Laboratory of Metabolic Adaptations to Exercise in Physiological and Pathological Conditions, Université Blaise Pascal - Clermont-Ferrand 2 (UBP), Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Federal University of Sao Paulo (Unifesp), Rzeszow University of Technology, Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Laboratoire de Psychologie Sociale et Cognitive (LAPSCO), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Centre de Recherche en Nutrition Humaine Auvergne [CHU Clermont-Ferrand] (CRNH A), French National University institute (IUF) UGE-CAM group, Service Médecine du Sport et Explorations Fonctionnelles [CHU Clermont-Ferrand], and CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand]
Subjects: Blood Glucose, 0301 basic medicine, Pediatrics, medicine.medical_specialty, Weight loss, Adolescent, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Blood Pressure, 030209 endocrinology & metabolism, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Multidisciplinary approach, medicine, Humans, Insulin, Child, ComputingMilieux_MISCELLANEOUS, 2. Zero hunger, 030109 nutrition & dietetics, Nutrition and Dietetics, medicine.diagnostic_test, business.industry, Physical activity, Pediatric obesity, Anthropometry, medicine.disease, Lipids, Obesity, Metabolic syndrome, Cardiometabolic impairments, Weight Reduction Programs, Blood pressure, Body Composition, Metabolome, Female, medicine.symptom, Lipid profile, business, Body mass index, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: International audience; The efficacy of weight loss interventions might be affected by the metabolic profile of adolescents with obesity. In this study, we hypothesized that the initial diagnosis of the MS, or its persistence after an intervention, will not reduce the efficacy of a 16-week multidisciplinary weight loss program. Ninety two adolescents (12-15 years; 62 girls) with obesity completed baseline anthropometric and body composition evaluation (DXA). Lipid profile, insulinemia, glycaemia and blood pressure were measured and metabolic syndrome (MS) diagnosed. The adolescents then followed a 4-month inpatient multidisciplinary weight management program. All measurements were performed before (T0) and after 4 months of intervention (T1). Body weight, body mass index (BMI) and percentage of fat mass (%FM) decreased significantly between T0 and T1 (P < .001), with no difference in fat-free mass (kg). All metabolic variables (except blood pressure) were improved. 47.6% of the whole sample presented with MS at baseline against 35.7% at T1. Body weight (P = 0.006), BMI (P = 0.0261), %FM (P = 0.0211), hip circumference (= 0.0131), BMI percentile (P = 0.0319), and diastolic blood pressure (P = 0.0365) showed a time x group interaction and their deltas (variations between T0 and T1) were significantly different between adolescents with and without MS at baseline. There was no significant difference between adolescents with persistent and nonpersistent MS except for Delta BMI percentile that deceased significantly more in the non persistent group (P = 0.0115). According to our results, the efficacy of weight loss interventions is not reduced in adolescents initially diagnosed with MS or different between those who present a persistent or nonpersistent MS after the intervention.
Published: 2021
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32. Decline in subarachnoid haemorrhage volumes associated with the first wave of the COVID-19 pandemic

Author: Ajit S. Puri, Allan Taylor, Huynh Le Vu, Tatemi Todaka, Teddy Y. Wu, Octavio M. Pontes-Neto, Eytan Raz, Pedro Lylyk, Jasmine Johann, Roberta Novakovic, Hormuzdiyar H. Dasenbrock, Francisco Mont’Alverne, Nobuyuki Sakai, Melanie Walker, Hugh Stephen Winters, Ossama Mansour, Yohei Takenobu, Gregory Walker, Miki Fujimura, Saif Bushnaq, Odysseas Kargiotis, Nabeel Herial, Markus A Möhlenbruch, Malveeka Sharma, Hiroshi Tokimura, Maxim Mokin, Jean Raymond, Michael D. Hill, Amal Abou-Hamden, Leonardo Renieri, Serdar Geyik, Yuri Sugiura, Luisa Fonseca, Roberto Crosa, Fabricio O Lima, Ameer E Hassan, Viet Quy Nguyen, Jane G. Morris, Steven W. Hetts, Jawad F. Kirmani, Matthew S. Tenser, Muhammad M. Qureshi, Gianmarco Bernava, Mahmoud H Mohammaden, Verónica V. Olavarría, Jun Deguchi, André Beer-Furlan, Steve M. Cordina, Hiroshi Yamagami, Mohamad Abdalkader, Toshiyuki Fujinaka, Clifford J. Eskey, Rotem Sivan-Hoffmann, Hao Zhang, Anirudh Kulkarni, Brendan Steinfort, Özlem Aykaç, Barbara Voetsch, Alex Brehm, Italo Linfante, Wenguo Huang, Omer Eker, M. Luis Silva, Pascal Jabbour, Lissa Peeling, Mollie McDermott, Pascale Lavoie, Kazutaka Sonoda, Thomas Devlin, Alicia C. Castonguay, Jin Soo Lee, Diogo C Haussen, Dileep R. Yavagal, Thanh N. Nguyen, Umair Rashid, Vasu Saini, Raghid Kikano, Hiroyuki Hashimoto, Masaaki Uno, Saima Ahmad, Artem Kaliaev, Eiji Hagashi, Ajay K. Wakhloo, Romain Bourcier, Ryoo Yamamoto, Jesse M. Thon, Georgios Tsivgoulis, Dorothea Altschul, Achmad Fidaus Sani, Satoshi Yamada, Varsha Singh, David S Liebeskind, Tatsuo Amano, Anchalee Churojana, Juan F. Arenillas, Junichi Iida, Charles C. Matouk, Nobuyuki Ohara, Osama O. Zaidat, Mario Martínez-Galdámez, Chandril Chugh, Don Frei, Vanessa Chalumeau, Brijesh P Mehta, Marios Psychogios, Anna Luisa Kühn, Leticia C Rebello, Xianjin Shang, Hosam Al-Jehani, Hiroki Fukuda, Hong Gee Roh, Gisele Sampaio Silva, Rakesh Khatri, Kenichi Todo, Amal Al Hashmi, Alex Bou Chebl, Sunil A Sheth, Zhongming Qiu, Oriana Cornett, Zhengzhou Yuan, Wazim Izzath, Hesham Masoud, Rodrigo Rivera, Michel Piotin, Vikram Huded, Mamoru Murakami, Mohamed Teleb, Viktor Szeder, Ruchir Shah, Dheeraj Gandhi, John Thornton, Michael Chen, Vitor Mendes Pereira, Nadia Hammami, Alice Ma, Anna M. Cervantes-Arslanian, James E. Siegler, Seby John, Carlos Ynigo Lopez, Mudassir Farooqui, David Ozretić, Takuya Kanamaru, Romain Guile, Daisuke Watanabe, Kosuke Miyake, Alejandro Rodriguez Vasquez, Patrick Nicholson, Yuki Yamamoto, William J. Mack, Naoto Kimura, Simon Mathew John, Robert Fahed, Yuji Matsumaru, David Y. Chung, Rishi Gupta, Ryuhei Kono, Michael Frankel, Victor S. Lopez Rivera, Johanna T. Fifi, Raul G Nogueira, Paolo Machi, Tudor G. Jovin, Jordi Blasco, Emma Griffin, Salvatore Mangiafico, Masafumi Morimoto, Jun Luo, Santiago Ortega-Gutierrez, Monika Killer-Oberpfalzer, Daniel Giansante Abud, Syed I. Hussain, Fawaz Al-Mufti, Yusuke Sugimura, Atilla Özcan Özdemir, Stephan A. Mayer, Sumeet Multani, Adel Alhazzani, Alhamza R Al-Bayati, Michael Kelly, Lee A Birnbaum, Shadi Yaghi, Jeyaraj D Pandian, Ji Man Hong, Junsuke Shimbo, Johnny Ho-Yin Wong, Elena A. Cora, Laura Mechtouff, Pedro S.C. Magalhães, Pablo M. Lavados, Yuichi Murayama, Dong Hun Shin, Simon Nagel, Ken Wong, Jose Antonio Fiorot, Jeremy Payne, Randall C. Edgell, Adrienne Weeks, CarMeN, laboratoire, Department of Neurology [Boston], Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Emory University School of Medicine, Emory University [Atlanta, GA], Boston University School of Medicine (BUSM), Boston University [Boston] (BU), National Hospital Organization Osaka National Hospital [Japon] (NHO Osaka National Hospital), Alexandria University [Alexandrie], Boston Medical Center [Boston, MA, USA] (BMC), Xinqiao Hospital [Chongqing, China] (XH), University of Cape Town, La Sagrada Familia Clinic/Clínica La Sagrada Familia [Buenos Aires, Argentina] (LSFC), Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Hospital General de Fortaleza [Fortaleza, Brazil] (HGF), Nottingham University Hospitals NHS Trust [UK], Kobe City Medical Center General Hospital [Kobe, Hyogo, Japan] (KCMCGH), Azienda Ospedaliero-Universitaria Careggi [Firenze, Toscana, Italy] (AOUC), University Hospital Centre Zagreb, Partenaires INRAE, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service de Neuroradiologie [CHU de Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Cleveland Clinic Abu Dhabi [Abou Dabi, Émirats arabes unis], Hôpital de Beaumont [Dublin, Ireland] (HB), Hospital-Estadual Central [Vitoria, Brazil] (HEC), Instituto de NeuroCirugía Asenjo, Institut national de neurologie Mongi-Ben Hamida [Tunis], Hue Central Hospital [Thua Thien Hue, Vietnam] (HCH), University of California [San Francisco] (UC San Francisco), University of California (UC), Centre hospitalier universitaire de Nantes (CHU Nantes), Washington University School of Medicine (WUSM), University of Washington [Seattle], Englewood Hospital and Medical Center [Englewood], Jefferson (Philadelphia University + Thomas Jefferson University), Westchester Medical Center [Valhalla, New York, USA] (WMC), Eskisehir Osmangazi University, University of Maryland School of Medicine, University of Maryland System, MAX Superspecialty Hospital [Saket, New Delhi, India] (MSH), Yale School of Medicine [New Haven, Connecticut] (YSM), Université Laval [Québec] (ULaval), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Rush University Medical Center [Chicago], Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), University of Toronto, NH Mazumdar Shah Medical Center [Bangalore, India] (NHMSMC), IMS Tokyo-Katsushika General Hospital [Tokyo, Japan], Gachon University [Seongnam, Korea] (GU), Hospital Municipal Sao Jose [Joinville, Santa Catarina, Brazil] (HMSJ), Lau Medical Center [Beirut, Lebanon] (LMC), University of Iowa [Iowa City], Royal Adelaide Hospital [Adelaide Australia], Kyorin University [Tokyo, Japan], Yokohama Brain and Spine Center [Yokohama, Japan] (YBSC), Dalhousie University [Halifax], Rambam Health Care Campus [Haifa, Israel], Centro Endovascular Neurologico Medica Uruguaya [Montevideo, Uruguay] (CENMU), Heidelberg University Hospital [Heidelberg], Imam Abdulrahman bin Faisal University [Alkhobar, Saudi Arabia] (IAFU), McGovern Medical School [Houston, TX, USA] (McGMS), The University of Texas Health Science Center at Houston (UTHealth), Cooper Medical School of Rowan University [Camden] (CMSRU), Airlangga University [Jawa Timur, Indonesia] (AU), University of Massachusetts Medical School [Worcester] (UMASS), University of Massachusetts System (UMASS), Geneva University Hospitals and Geneva University, Universidade de São Paulo = University of São Paulo (USP), Beth Israel Lahey Health [Burlington, MA, USA] (BILH), New York University School of Medicine (NYU Grossman School of Medicine), Memorial Neuroscience Institute [Pembroke Pines, FL, USA] (MNI), Iwate Prefectural Central Hospital [Morioka, Iwate, Japan] (IPCH), Japanese Red Cross Musashino Hospital [Tokyo], Ajou University, University of Ottawa [Ottawa], Saga-ken Medical Centre Koseikan [Saga, Japan] (SMCK), University of South Alabama, Konkuk University [Seoul], Royal Free Hospital [London, UK], Hospital Clinico Universitario de Valladolid [Castilla y León, Spain] (HCUV), Universidad de Valladolid [Valladolid] (UVa), Instituto de Ciencia de Materiales de Aragón [Saragoza, España] (ICMA-CSIC), University of Zaragoza - Universidad de Zaragoza [Zaragoza], Hospital Clínic de Barcelona [Catalonia, Spain], Centro Hospitalar Universitário de São João [Porto], Christchurch Hospital [Christchurch, New Zealand] (CH), University Hospital Basel [Basel], University of Southern California (USC), Kohnan Hospital - Sendai [Miyagi, Japan], University of Texas Southwestern Medical Center [Dallas], Nara City Hospital [Nara, Japan] (NCH), Toyonaka Municipal Hospital [Osaka, Japan] (TMH), Kagoshima City Hospita [Kagoshima, Japan] (KCH), Texas Tech University System [Lubbock, TX, USA] (TTUS), University of Saskatchewan [Saskatoon] (U of S), National Institute of Information and Communications Technology [Tokyo, Japan] (NICT), Royal Prince Alfred Hospital [Camperdown, Australia] (RPAH), Banner Desert Medical Center [Mesa, AZ, USA] (BDMC), Japanese Red Cross Matsue Hospital [Shimane, Japan] (JRCMH), Shiroyama Hospital [Osaka, Japan] (SH), Niigata City General Hospital [Niigata, Japan] (NCGH), Sugimura Hospital [Kumamoto, Japan] (SH), Kawasaki Medical School [Kurashiki, Japan] (KMS), Osaka Red Cross Hospital [Osaka, Japan] (ORCH), Université de Tsukuba = University of Tsukuba, Saiseikai Central Hospital [Tokyo, Japan] (SCH), Kinikyo Chuo Hospital - Sapporo [Hokkaido, Japan] (KCHS), NTT Medical Center Tokyo [Tokyo, Japan] (NTTMCT), Yokohama Shintoshi Neurosurgical Hospital [Yokohama, Japan]. (YSNH), Osaka General Medical Center [Osaka, Japan] (OGMC), University of Miami Leonard M. Miller School of Medicine (UMMSM), Bon Secours Mercy Health System [Toledo, OH, USA] (BSMHS), Maoming City Hospital [Guandong, China] (MCH), Miami Cardiac & Vascular Institute [Miami, FL, USA] (MC&VI), Hackensack University Medical Center [Hackensack], David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), University of Tennessee [Chattanooga] (UTC), The University of Texas at San Antonio (UTSA), Mianyang 404 Hospital [Sichuan, China] (M404H), Siriraj Hosital - Mahidol University [Bangkok, Thailand] (SHMU), SUNY Upstate Medical University, State University of New York (SUNY), Royal North Shore Hospital (RNSH), The University of Texas Rio Grande Valley [Harlingen, TX, USA] (UTRGV), Khoula Hospital [Muscat, Oman] (Ministry of Health - KH), University of Michigan [Ann Arbor], University of Michigan System, University of South Florida [Tampa] (USF), Henry Ford Health System [Detroit, MI, USA] (HFHS), Metropolitan Hospital [Piraeus, Greece] (MH), National and Kapodistrian University of Athens (NKUA), Maine Medical Center, Dartmouth Hitchcock Medical Center [Lebanon, NH, USA] (DHMC), Centro Universitário Feevale (BRAZIL), The Valley Hospital [Ridgewood, NJ, USA] (TVH), St Joseph's University Medical Center [Paterson, NJ, USA] (StJUMC), Christian Medical College and Hospital Ludhiana [Punjab, India] (CMCHL), Universidad del Desarrollo, University Graduate School of Medicine [Osaka, Japan], Tokushima University, Universidade Federal de São Paulo, Istanbul Aydin University [İstanbul, Turkey] (IAU), Swedish Medical Center [Englewood, CO, USA] (SMC), Bayhealth Medical Center [Dover, DE, USA] (BMC), Saiseikai Fukuoka General Hospital [Fukuoka, Japan] (SFGH), Osaka Rosai Hospital - Sakai [Osaka, Japan] (ORHS), King Saud University [Riyadh] (KSU), Mount Sinai Health System, University of Calgary, Huzhou University [Zhejiang], The Affiliated Hospital of Southwest Medical University - Luzhou [Sichuan, China] (TAHSMUL), Yijishan Hospital of Wannan Medical College [Wuhu, Anhui, China] (YHWMC), University of Toledo, WellStar Health System [Marietta, GA, USA] (WHS), Institut National de la Recherche Scientifique [Québec] (INRS), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), SVIN COVID-19 Registry, the Middle East North Africa Stroke and Interventional Neurotherapies Organization (MENA-SINO), Japanese Society of Vascular and Interventional Neurology Society (JVIN), University of California [San Francisco] (UCSF), University of California, Yale University School of Medicine, University of São Paulo (USP), and University of California-University of California
Subjects: [SDV]Life Sciences [q-bio], COVID-19, Subarachnoid Hemorrhage* / diagnostic imaging, 030204 cardiovascular system & hematology, Intracranial Aneurysm* / therapy, lcsh:RC346-429, 0302 clinical medicine, Pandemic, Myocardial infarction, Prospective Studies, Stroke, Original Research, 3. Good health, [SDV] Life Sciences [q-bio], Treatment Outcome, Intracranial Aneurysm* / diagnostic imaging, Cardiology, Subarachnoid haemorrhage, haemorrhage, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Subgroup analysis, subarachnoid, Intracranial Aneurysm* / epidemiology, 03 medical and health sciences, Aneurysm, Internal medicine, medicine, Humans, coil, cardiovascular diseases, Pandemics, lcsh:Neurology. Diseases of the nervous system, Retrospective Studies, business.industry, SARS-CoV-2, Intracranial Aneurysm, Subarachnoid Hemorrhage, medicine.disease, infection, nervous system diseases, Mechanical thrombectomy, Cross-Sectional Studies, aneurysm, Neurology (clinical), Subarachnoid Hemorrhage* / epidemiology, business, 030217 neurology & neurosurgery
Abstract: BackgroundDuring the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study’s objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines.MethodsWe conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March–31 May 2020. The prior 1-year control period (1 March–31 May 2019) was obtained to account for seasonal variation.FindingsThere was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI −24.3% to −20.7%, pInterpretationThere was a relative decrease in the volume of SAH hospitalisations, aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic. These findings in SAH are consistent with a decrease in other emergencies, such as stroke and myocardial infarction.
Published: 2021
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33. Food and microbiota metabolites associate with cognitive decline in older subjects: A 12-year prospective study

Author: Alex Sánchez-Pla, Aniko Korosi, Mireia Urpi-Sarda, Andrea Du Preez, Mercè Pallàs, Cécilia Samieri, Silvie R. Ruigrok, Sandrine Thuret, Raúl González-Domínguez, Francisco Carmona, Claudine Manach, Dorrain Yanwen Low, Ludwig Aigner, Paul J. Lucassen, Pol Castellano-Escuder, Cristina Andres-Lacueva, Sophie Lefèvre-Arbogast, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Structural and Functional Plasticity of the nervous system (SILS, FNWI), Universitat de Barcelona (UB), Instituto de Salud Carlos III [Madrid] (ISC), Laboratoire de Biotechnologie et Microbiologie Appliquée (LBMA), Université Bordeaux Segalen - Bordeaux 2-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), King‘s College London, University of Amsterdam [Amsterdam] (UvA), and Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU)
Subjects: Gerontology, Microbiota intestinal, Gut flora, Benton Visual Retention Test, medicine, Metabolome, Humans, Dementia, Cognitive Dysfunction, Prospective Studies, Cognitive decline, Prospective cohort study, Gastrointestinal microbiome, Aged, food metabolome, gut microbiota, biology, business.industry, Microbiota, Envelliment cerebral, Neuropsychology, cognitive decline, medicine.disease, biology.organism_classification, metabolomics, Gastrointestinal Microbiome, Diet, Food, Cohort, Aging brain, Dieta, diet, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Food Science, Biotechnology
Abstract: SCOPE: Diet is considered an important modulator of cognitive decline and dementia, but the available evidence is, however, still fragmented and often inconsistent.METHODS AND RESULTS: The article studies the long-term prospective Three-City Cohort, which consists of two separate nested case-control sample sets from different geographic regions (Bordeaux, n = 418; Dijon, n = 424). Cognitive decline is evaluated through five neuropsychological tests (Mini-Mental State Examination, Benton Visual Retention Test, Isaac's Set Test, Trail-Making Test part A, and Trail-Making Test part B). The food-related and microbiota-derived circulating metabolome is studied in participants free of dementia at baseline, by subjecting serum samples to large-scale quantitative metabolomics analysis. A protective association is found between metabolites derived from cocoa, coffee, mushrooms, red wine, the microbial metabolism of polyphenol-rich foods, and cognitive decline, as well as a negative association with metabolites related to unhealthy dietary components, such as artificial sweeteners and alcohol.CONCLUSION: These results provide insight into the early metabolic events that are associated with the later risk to develop cognitive decline within the crosstalk between diet, gut microbiota and the endogenous metabolism, which can help identify potential targets for preventive and therapeutic strategies to preserve cognitive health.
Published: 2021
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34. Pathologically reduced neural flexibility recovers during psychotherapy of OCD patients

Author: Brigitte Kravanja-Spannberger, Helmut Schöller, Benjamin Aas, Viktor K. Jirsa, Günter Schiepek, Barbara Stöger-Schmidinger, Anna Kastinger, Sarah Said-Yürekli, Kathrin Viol, Eva-Maria Reiter, Lisa Kronbichler, Martin Kronbichler, Demian Battaglia, Wolfgang Aichhorn, Ludwig-Maximilians-Universität München (LMU), Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Otten, Lisa
Subjects: Obsessive-Compulsive Disorder, Psychotherapist, Neural flexibility, Cognitive Neuroscience, Computer applications to medicine. Medical informatics, R858-859.7, Psychological health, Neural activity, Neural Pathways, medicine, Humans, Radiology, Nuclear Medicine and imaging, Dynamic functional connectivity (dFC), RC346-429, Depression (differential diagnoses), Dynamic functional connectivity, Brain Mapping, OCD, Depression, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, fMRI, Brain, Repeated measures design, Flexibility (personality), Regular Article, Inpatient psychotherapy, Magnetic Resonance Imaging, Psychotherapy, Neurology, Anxiety, Neurology (clinical), Neurology. Diseases of the nervous system, medicine.symptom, Psychology
Abstract: Highlights • Psychiatric impairment is associated with decreased neural flexibility. • Psychotherapy was able to increase the neural flexibility of the patients. • Psychotherapy should increase adaptivity of cognitive-emotional-behavioral patterns., Flexibility is a key feature of psychological health, allowing the individual to dynamically adapt to changing environmental demands, which is impaired in many psychiatric disorders like obsessive–compulsive disorder (OCD). Adequately responding to varying demands requires the brain to switch between different patterns of neural activity, which are represented by different brain network configurations (functional connectivity patterns). Here, we operationalize neural flexibility as the dissimilarity between consecutive connectivity matrices of brain regions (jump length). In total, 132 fMRI scans were obtained from 17 patients that were scanned four to five times during inpatient psychotherapy, and from 17 controls that were scanned at comparable time intervals. Significant negative correlations were found between the jump lengths and the symptom severity scores of OCD, depression, anxiety, and stress, suggesting that high symptom severity corresponds to inflexible brain functioning. Further analyses revealed that impaired reconfiguration (pattern stability) of the brain seems to be more related to general psychiatric impairment rather than to specific symptoms, e.g., of OCD or depression. Importantly, the group × time interaction of a repeated measures ANOVA was significant, as well as the post-hoc paired t-tests of the patients (first vs. last scan). The results suggest that psychotherapy is able to significantly increase the neural flexibility of patients. We conclude that psychiatric symptoms like anxiety, stress, depression, and OCD are associated with an impaired adaptivity of the brain. In general, our results add to the growing evidence that dynamic functional connectivity captures meaningful properties of brain functioning.
Published: 2021
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35. Early Evaluation of Organ Failure Using MELD-XI in Critically Ill Elderly COVID-19 Patients

Author: Johanna Hornemann, Christian Jung, Malte Kelm, Sandra Oeyen, Dylan W. de Lange, Michael Joannidis, Brian Marsh, Wojciech Szczeklik, Bernardo Bollen Pinto, Stephan Binneboessel, Finn H. Andersen, Bernhard Wernly, Michael Beil, Philipp Heinrich Baldia, Muhammed Elhadi, Hans Flaatten, Peter Vernon van Heerden, Raphael Romano Bruno, Eumorfia Kondili, Georg Wolff, Ariane Boumendil, Rui Moreno, Jesper Fjølner, Susannah Leaver, Bertrand Guidet, Joerg C. Schefold, Sigal Sviri, Antonio Artigas, Jakob Wollborn, Gestionnaire, Hal Sorbonne Université, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), University of Bergen (UiB), Aarhus University Hospital, CIBER de Epidemiología y Salud Pública (CIBERESP), Geneva University Hospitals and Geneva University, Hadassah Hebrew University Medical Center [Jerusalem], The Hebrew University of Jerusalem (HUJ), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Ghent University Hospital, Mater Misericordiae University Hospital (The Mater Hospital), NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), St George’s University Hospitals, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Réanimation Médicale [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
Subjects: medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Physiology, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Critical Illness, [SDV]Life Sciences [q-bio], Disease, Logistic regression, Severity of Illness Index, chemistry.chemical_compound, Physiology (medical), Intensive care, Internal medicine, medicine, Humans, 610 Medicine & health, Aged, Creatinine, business.industry, Critically ill, SARS-CoV-2, Confounding, COVID-19, Hematology, Prognosis, body regions, [SDV] Life Sciences [q-bio], chemistry, Cardiology and Cardiovascular Medicine, business
Abstract: International audience; PURPOSE Critically ill elderly patients who suffer from Sars-CoV-2 disease are at high risk for organ failure. The modified MELD-XI score has not been evaluated for outcome prediction in these most vulnerable patients. METHODS The Corona Virus disease (COVID19) in Very Elderly Intensive Care Patients study (COVIP, NCT04321265) prospectively recruited patients on intensive care units (ICU), who were = 70 years. Data were collected from March 2020 to February 2021. The MELD-XI score was calculated using the highest serum bilirubin and creatinine on ICU admission. Univariate and multivariable logistic regression analyses were performed to assess associations between the MELD-XI score and mortality. The primary outcome was 30-day-mortality, the secondary outcomes were ICU- and 3-month-mortality. RESULTS In total, data from 2,993 patients were analyzed. Most patients had a MELD-XI
Published: 2021
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36. Left Ventricular Unloading Is Associated With Lower Mortality in Patients With Cardiogenic Shock Treated With Venoarterial Extracorporeal Membrane Oxygenation

Author: Schrage, Benedikt, Becher, Peter, Bernhardt, Alexander, Bezerra, Hiram, Blankenberg, Stefan, Brunner, Stefan, Colson, Pascal, Cudemus Deseda, Gaston, Dabboura, Salim, Eckner, Dennis, Eden, Matthias, Eitel, Ingo, Frank, Derk, Frey, Norbert, Funamoto, Masaki, Goßling, Alina, Graf, Tobias, Hagl, Christian, Kirchhof, Paulus, Kupka, Danny, Landmesser, Ulf, Lipinski, Jerry, Lopes, Mathew, Majunke, Nicolas, Maniuc, Octavian, McGrath, Daniel, Möbius-Winkler, Sven, Morrow, David, Mourad, Marc, Noel, Curt, Nordbeck, Peter, Orban, Martin, Pappalardo, Federico, Patel, Sandeep, Pauschinger, Matthias, Pazzanese, Vittorio, Reichenspurner, Hermann, Sandri, Marcus, Schulze, P. Christian, H.G. Schwinger, Robert, Sinning, Jan-Malte, Aksoy, Adem, Skurk, Carsten, Szczanowicz, Lukasz, Thiele, Holger, Tietz, Franziska, Varshney, Anubodh, Wechsler, Lukas, Westermann, Dirk, University Heart Center [Hamburg], German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), University of South Florida [Tampa] (USF), Klinikum der Ludwig-Maximilians-Universität, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Massachusetts General Hospital [Boston], Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), University Medical Center of Schleswig–Holstein = Universitätsklinikum Schleswig-Holstein (UKSH), Kiel University, University of Birmingham [Birmingham], University Hospitals Birmingham [Birmingham, Royaume-Uni], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], University of California [San Diego] (UC San Diego), University of California (UC), Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Heart Centre Leipzig, Universität Leipzig [Leipzig], University Hospital of Würzburg, Jena University Hospital [Jena], Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), St. Rita's Medical Center [Lima], Klinikum Weiden, University Hospital Bonn, Herrada, Anthony, Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), and University of California
Subjects: [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, cardiogenic, shock, extracorporeal membrane oxygenation, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Abstract: International audience; Background: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used to treat cardiogenic shock. However, VA-ECMO might hamper myocardial recovery. The Impella unloads the left ventricle. This study aimed to evaluate whether left ventricular unloading in patients with cardiogenic shock treated with VA-ECMO was associated with lower mortality. Methods: Data from 686 consecutive patients with cardiogenic shock treated with VA-ECMO with or without left ventricular unloading using an Impella at 16 tertiary care centers in 4 countries were collected. The association between left ventricular unloading and 30-day mortality was assessed by Cox regression models in a 1:1 propensity score–matched cohort. Results: Left ventricular unloading was used in 337 of the 686 patients (49%). After matching, 255 patients with left ventricular unloading were compared with 255 patients without left ventricular unloading. In the matched cohort, left ventricular unloading was associated with lower 30-day mortality (hazard ratio, 0.79 [95% CI, 0.63–0.98]; P =0.03) without differences in various subgroups. Complications occurred more frequently in patients with left ventricular unloading: severe bleeding in 98 (38.4%) versus 45 (17.9%), access site–related ischemia in 55 (21.6%) versus 31 (12.3%), abdominal compartment in 23 (9.4%) versus 9 (3.7%), and renal replacement therapy in 148 (58.5%) versus 99 (39.1%). Conclusions: In this international, multicenter cohort study, left ventricular unloading was associated with lower mortality in patients with cardiogenic shock treated with VA-ECMO, despite higher complication rates. These findings support use of left ventricular unloading in patients with cardiogenic shock treated with VA-ECMO and call for further validation, ideally in a randomized, controlled trial.
Published: 2020
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37. Impact of PD-L1 Scores and Changes on Clinical Outcome in Rectal Cancer Patients Undergoing Neoadjuvant Chemoradiotherapy

Author: Richard Greil, Amos Kirilovsky, Tarkan Jäger, Franck Pagès, Franz Xaver Singhartinger, Lukas Weiss, Daniel Neureiter, Florian Huemer, Markus Steiner, Nadja Zaborsky, A. Dinnewitzer, Gabriel Rinnerthaler, Wolfgang Iglseder, Verena Schlintl, Carine El Sissy, Eckhard Klieser, Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Hôpital Européen Georges Pompidou [APHP] (HEGP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)
Subjects: medicine.medical_specialty, programmed death-ligand 1, Multivariate analysis, Colorectal cancer, lcsh:Medicine, [SDV.CAN]Life Sciences [q-bio]/Cancer, TPS, Gastroenterology, survival, Article, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, PD-L1, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Medicine, 030212 general & internal medicine, biology, business.industry, lcsh:R, Hazard ratio, IC, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, General Medicine, medicine.disease, 3. Good health, Clinical trial, 030220 oncology & carcinogenesis, biology.protein, CPS, business, Neoadjuvant chemoradiotherapy
Abstract: Reports on the prognostic role of programmed death-ligand 1 (PD-L1) expression in rectal cancer are controversial. We investigated expression patterns and changes of PD-L1 in rectal cancer patients undergoing neoadjuvant chemoradiotherapy (CRT). Seventy-two patients diagnosed with rectal cancer and/or treated with fluorouracil-based neoadjuvant CRT at the Department of Internal Medicine III of the Paracelsus Medical University Salzburg (Austria) between January 2003 and October 2012 were included. PD-L1 scoring was performed according to the tumor proportion score (TPS), combined positive score (CPS), and immune cell score (IC). PD-L1 TPS prior to neoadjuvant CRT had a statistically significant impact on survival (median: &le, 1%: 95.4 months (95% CI: 51.8&mdash, not reached) vs. &gt, 1%: not reached, p = 0.03, log-rank). Patients with a PD-L1 TPS &le, 1% prior to and after CRT showed an inferior survival compared to all other patients (median: 56.7 months (95% CI: 51.4&mdash, not reached) vs. not reached, p = 0.005, log-rank). In multivariate analysis, PD-L1 TPS prior to neoadjuvant CRT (&gt, 1% vs. &le, 1%, hazard ratio: 0.29 (95% CI: 0.11&ndash, 0.76), p = 0.01) remained independently associated with survival. In conclusion, low PD-L1 TPS was associated with inferior survival in rectal cancer patients undergoing neoadjuvant CRT. A prospective validation of the prognostic value of PD-L1 expression in rectal cancer patients within a clinical trial is necessitated.
Published: 2020
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38. Caffeine Compromises Proliferation of Human Hippocampal Progenitor Cells

Author: Claudine Manach, Mireia Urpi-Sarda, Andrea Du Preez, Raúl González-Domínguez, Vikki Houghton, Chiara De Lucia, Barbara Altendorfer, Cécilia Samieri, Ludwig Aigner, Cristina Andres-Lacueva, Sandrine Thuret, Sophie Lefèvre-Arbogast, Dorrain Yanwen Low, Aniko Korosi, Silvie R. Ruigrok, Paul J. Lucassen, King‘s College London, Université de Bordeaux (UB), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Nutrition Humaine (UNH), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Universitat de Barcelona (UB), Swammerdam Institute for Life Sciences (SILS), University of Amsterdam [Amsterdam] (UvA), Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Technische Universität Dresden = Dresden University of Technology (TU Dresden), Medical Research Council UK (MRC) MR/N030087/1French National Research Agency (ANR)ANR-15-HDHL-0002-05PCIN-2015-229-MINECOJPI-HDHL (CiberFES-Cofund by FEDER Program from EU) 2017SGR1546JPI-HDHL (ICREA 2018 Academia Award from the Generalitat de Catalunya) BMWFW BMWFW-10.420/0009-WF/V/3c/2015Urban Mental Health RPA from the University of Amsterdam, and Structural and Functional Plasticity of the nervous system (SILS, FNWI)
Subjects: 0301 basic medicine, hippocampal progenitor proliferation, medicine.medical_specialty, Immunocytochemistry, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Hippocampal formation, LEHA, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Caffeine, medicine, Metabolites, Cognitive decline, Progenitor cell, lcsh:QH301-705.5, Progenitor, caffeine, Biochemical markers, Cell Biology, Metabòlits, adult hippocampal neurogenesis, Neural stem cell, 3. Good health, 030104 developmental biology, Endocrinology, lcsh:Biology (General), chemistry, Apoptosis, Cafeïna, 030220 oncology & carcinogenesis, Marcadors bioquímics, hippocampal progenitor integrity, diet, Developmental Biology
Abstract: International audience; The age-associated reduction in the proliferation of neural stem cells (NSCs) has been associated with cognitive decline. Numerous factors have been shown to modulate this process, including dietary components. Frequent consumption of caffeine has been correlated with an increased risk of cognitive decline, but further evidence of a negative effect on hippocampal progenitor proliferation is limited to animal models. Here, we used a human hippocampal progenitor cell line to investigate the effects of caffeine on hippocampal progenitor integrity and proliferation specifically. The effects of five caffeine concentrations (0 mM = control, 0.1 mM ∼ 150 mg, 0.25 mM ∼ 400 mg, 0.5 mM ∼ 750 mg, and 1.0 mM ∼ 1500 mg) were measured following acute (1 day) and repeated (3 days) exposure. Immunocytochemistry was used to quantify hippocampal progenitor integrity (i.e., SOX2- and Nestin-positive cells), proliferation (i.e., Ki67-positive cells), cell count (i.e., DAPI-positive cells), and apoptosis (i.e., CC3-positive cells). We found that progenitor integrity was significantly reduced in supraphysiological caffeine conditions (i.e., 1.0 mM ∼ 1500 mg), but relative to the lowest caffeine condition (i.e., 0.1 mM ∼ 150 mg) only. Moreover, repeated exposure to supraphysiological caffeine concentrations (i.e., 1.0 mM ∼ 1500 mg) was found to affect proliferation, significantly reducing % Ki67-positive cells relative to control and lower caffeine dose conditions (i.e., 0.1 mM ∼ 150 mg and 0.25 mM ∼ 400 mg). Caffeine treatment did not influence apoptosis and there were no significant differences in any measure between lower doses of caffeine (i.e., 0.1 mM, 0.25 mM, 0.5 mM) - representative of daily human caffeine intake - and control conditions. Our study demonstrates that dietary components such as caffeine can influence NSC integrity and proliferation and may be indicative of a mechanism by which diet affects cognitive outcomes.
Published: 2020
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39. Frailty assessment in very old intensive care patients: the Hospital Frailty Risk Score answers another question

Author: Hans Flaatten, Bertrand Guidet, Christian Jung, Bernhard Wernly, Raphael Romano Bruno, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Service de Réanimation Médicale [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], University of Bergen (UiB), Haukeland University Hospital, and Gestionnaire, Hal Sorbonne Université
Subjects: medicine.medical_specialty, Critical Care, Pain medicine, [SDV]Life Sciences [q-bio], MEDLINE, Critical Care and Intensive Care Medicine, 03 medical and health sciences, 0302 clinical medicine, Cognition, Risk Factors, Intensive care, Anesthesiology, medicine, Humans, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Framingham Risk Score, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Frailty, business.industry, 030208 emergency & critical care medicine, Hospitals, 3. Good health, Frailty assessment, [SDV] Life Sciences [q-bio], Intensive Care Units, Emergency medicine, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience
Published: 2020
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40. Impact of Antiplatelet Therapy During Endovascular Therapy for Tandem Occlusions

Author: Zhu, François, Anadani, Mohammad, Labreuche, Julien, Spiotta, Alejandro, Turjman, Francis, Piotin, Michel, Steglich-Arnholm, Henrik, Holtmannspötter, Markus, Taschner, Christian, Eiden, Sebastian, Haussen, Diogo, Nogueira, Raul, Papanagiotou, Panagiotis, Boutchakova, Maria, Siddiqui, Adnan, Lapergue, Bertrand, Dorn, Franziska, Cognard, Christophe, Killer-Oberpfalzer, Monika, Mangiafico, Salvatore, Ribo, Marc, Psychogios, Marios, Labeyrie, Marc-Antoine, Mazighi, Mikael, Biondi, Alessandra, Anxionnat, René, Bracard, Serge, Richard, Sébastien, Gory, Benjamin, Grossberg, Jonathan Andrew, Guenego, Adrien, Darcourt, Julien, Vukasinovic, Isabelle, Pomero, Elisa, Davies, Jason, Renieri, Leonardo, Hecker, Corentin, Muchada, Maria Muchada, Consoli, Arturo, Rodesch, Georges, Houdart, Emmanuel, Lockau, Johanna, Kastrup, Andreas, Blanc, Raphaël, Redjem, Hocine, Behme, Daniel, Shallwani, Hussain, Christopher, Maurer, Mione, Gioia, Humbertjean, Lisa, Lacour, Jean-Christophe, Riou-Comte, Nolwenn, Derelle, Anne-Laure, Tonnelet, Romain, Liao, Liang, Département de neuroradiologie diagnostique et thérapeutique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Medical University of South Carolina [Charleston] (MUSC), Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille, Hospices Civils de Lyon (HCL), Hôpital Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Rigshospitalet [Copenhagen], Copenhagen University Hospital, Freiburg University Medical Center, Emory University School of Medicine, Emory University [Atlanta, GA], Klinikum Bremen-Mitte, University at Buffalo [SUNY] (SUNY Buffalo), State University of New York (SUNY), Hôpital Foch [Suresnes], University-Hospital Munich-Großhadern [München], Service de neuroradiologie [CHU Toulouse], CHU Toulouse [Toulouse], Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Careggi University Hospital [Florence, Italie], Vall d'Hebron University Hospital [Barcelona], University Medical Center Göttingen (UMG), Service de Neuroradiologie [CHU Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Service de Neuroradiologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de neurologie [CHRU Nancy], Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Neuroradiologie Interventionnelle et Fonctionnelle, Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Lorraine (UL), Service d’Anatomie Pathologique [CHRU Nancy], Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Universitäts Klinikum Freiburg = University Medical Center Freiburg (Uniklinik), Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV]Life Sciences [q-bio], cardiovascular diseases, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, [SHS]Humanities and Social Sciences
Abstract: International audience; Background and Purpose- Antiplatelet agents could be used in the setting of endovascular therapy for tandem occlusions to reduce the risk of de novo intracranial embolic migration, reocclusion of the extracranial internal carotid artery lesion, or in-stent thrombosis in case of carotid stent placement but have to be balanced with the intracerebral hemorrhagic transformation risk. In this study, we aim to investigate the impact of acute antiplatelet therapy administration on outcomes during endovascular therapy for anterior circulation tandem occlusions. Methods- This is a retrospective analysis of a collaborative pooled analysis of 11 prospective databases from the multicenter observational TITAN registry (Thrombectomy in Tandem Lesions). Patients were divided into groups based on the number of antiplatelet administered during endovascular therapy. The primary outcome was favorable outcome, defined as a modified Rankin Scale score of 0 to 2 at 90 days. Results- This study included a total of 369 patients; 145 (39.3%) did not receive any antiplatelet agent and 224 (60.7%) received at least 1 antiplatelet agent during the procedure. Rate of favorable outcome was nonsignificantly higher in patients treated with antiplatelet therapy (58.3%) compared with those treated without antiplatelet (46.0%; adjusted odds ratio, 1.38 [95% CI, 0.78-2.43]; P=0.26). Rate of 90-day mortality was significantly lower in patients treated with antiplatelet therapy (11.2% versus 18.7%; adjusted odds ratio, 0.47 [95% CI, 0.22-0.98]; P=0.042), without increasing the risk of any intracerebral hemorrhage. Successful reperfusion (modified Thrombolysis in Cerebral Ischemia score 2b-3) rate was significantly better in the antiplatelet therapy group (83.9% versus 71.0%; adjusted odds ratio, 1.89 [95% CI, 1.01-3.64]; P=0.045). Conclusions- Administration of antiplatelet therapy during endovascular therapy for anterior circulation tandem occlusions was safe and was associated with a lower 90-day mortality. Optimal antiplatelet therapy remains to be assessed, especially when emergent carotid artery stenting is performed. Further randomized controlled trials are needed.
Published: 2020
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41. Head or Neck First? Speed and Rates of Reperfusion in Thrombectomy for Tandem Large Vessel Occlusion Strokes

Author: Serge Bracard, Mikael Mazighi, René Anxionnat, Salvatore Mangiafico, Panagiotis Papanagiotou, Christian Taschner, Christophe Cognard, Alessandra Biondi, Monika Killer, Bertrand Lapergue, Benjamin Gory, Diogo C Haussen, Markus Holtmannspötter, Maria Boutchakova, Marios Psychogios, Michel Piotin, Adnan H. Siddiqui, Jonathan A. Grossberg, Marc-Antoine Labeyrie, Franziska Dorn, Francis Turjman, Raul G Nogueira, Alejandro M Spiotta, Marc Ribó, Sebastian Eiden, Henrik Steglich-Arnholm, Sébastien Richard, Julien Labreuche, Emory University [Atlanta, GA], Hospices Civils de Lyon (HCL), Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Rigshospitalet [Copenhagen], Copenhagen University Hospital, Universitäts Klinikum Freiburg = University Medical Center Freiburg (Uniklinik), Klinikum Bremen-Mitte, State University of New York (SUNY), Hôpital Foch [Suresnes], University-Hospital Munich-Großhadern [München], Service Neuroradiologie Diagnostique et Thérapeutique [CHU Toulouse], Pôle imagerie médicale [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Azienda Ospedaliero-Universitaria Careggi [Firenze] (AOUC), Vall d'Hebron University Hospital [Barcelona], University Medical Center Göttingen (UMG), Medical University of South Carolina [Charleston] (MUSC), Service de Neuroradiologie [CHU Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], 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, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Département de neuroradiologie diagnostique et thérapeutique [CHRU Nancy], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Freiburg University Medical Center, Neuroradiologie Diagnostique et Thérapeutique [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Azienda Ospedaliero-Universitaria Careggi (AOU Careggi), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord
Subjects: medicine.medical_specialty, medicine.medical_treatment, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 030204 cardiovascular system & hematology, Revascularization, Lesion, 03 medical and health sciences, 0302 clinical medicine, medicine.artery, Angioplasty, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Stroke, Original Paper, Cerebral infarction, business.industry, Stent, Thrombolysis, medicine.disease, 3. Good health, Surgery, Neurology (clinical), medicine.symptom, Internal carotid artery, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background: We aim to evaluate the speed and rates of reperfusion in tandem large vessel occlusion acute stroke patients undergoing upfront cervical lesion treatment (Neck-First: angioplasty and/or stent before thrombectomy) as compared to direct intracranial occlusion therapy (Head-First) in a large international multicenter cohort. Methods: The Thrombectomy In TANdem Lesions (TITAN) collaboration pooled individual data of prospectively collected thrombectomy international databases for all consecutive anterior circulation tandem patients who underwent emergent thrombectomy. The co-primary outcome measures were rates of successful reperfusion (modified Thrombolysis in Cerebral Infarction 2b/3) and time from groin puncture to successful reperfusion. Results: In total, 289 patients with tandem atherosclerotic etiology were included in the analysis (182 Neck-First and 107 Head-First patients). Except for differences in the Alberta Stroke Program Early CT Score (ASPECTS; median 8 [range 7–10] Neck-First vs. 7 [range 6–8] Head-First; p < 0.001) and cervical internal carotid artery (ICA) lesion severity (complete occlusion in 35% of the Neck-First vs. 57% of the Head-First patients; p < 0.001), patient characteristics were well balanced. After adjustments, there was no difference in successful reperfusion rates between the study groups (odds ratio associated with Neck-First: 1.18 [95% confidence interval, 0.60–2.17]). The time to successful reperfusion from groin puncture was significantly shorter in the Head-First group after adjustments (median 56 min [range 39–90] vs. 70 [range 50–102]; p = 0.001). No significant differences in the rates of full reperfusion, symptomatic hemorrhage, 90-day independence, or mortality were observed. Sensitivity analysis excluding patients with complete cervical ICA occlusion yielded similar results. Conclusions: The upfront approach of the intracranial lesion in patients with tandem large vessel occlusion strokes leads to similar reperfusion rates but faster reperfusion as compared to initial cervical revascularization followed by mechanical thrombectomy. Controlled studies are warranted.
Published: 2020
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42. European confederation of medical mycology expert consult-An ECMM excellence center initiative

Author: Oliver A. Cornely, Jean-Michel Molina, Katrien Lagrou, Isabel Spriet, Dimitrios P. Kontoyiannis, Malcolm Richardson, Peter-Michael Rath, Riina Rautemaa-Richardson, David W. Denning, Sanja Pleško, Joerg Steinmann, Philipp Koehler, Esther Segal, Jean-Pierre Gangneux, Blandine Denis, Juergen Prattes, Danila Seidel, Robert Krause, Martin Hoenigl, Cornelia Lass-Flörl, Johan Maertens, Ivana Mareković, Jacques F. Meis, Paul E. Verweij, University of Cologne, Laboratoire de Parasitologie-Mycologie [CHU Saint Louis, Paris], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Manchester [Manchester], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Karl-Franzens-Universität Graz, University of California [San Diego] (UC San Diego), University of California, Rice University [Houston], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Universität Innsbruck [Innsbruck], University of Zagreb, Canisius-Wilhelmina Hospital [Nijmegen, The Netherlands], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Universitätsklinikum Essen [Universität Duisburg-Essen] (Uniklinik Essen), Manchester University NHS Foundation Trust (MFT), Tel Aviv University [Tel Aviv], Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Radboud University Medical Center [Nijmegen], Jonchère, Laurent, Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), University of California (UC), and Tel Aviv University (TAU)
Subjects: 0301 basic medicine, Antifungal Agents, Candida auris, Candidemia, aspergillosis, azole-resistance, candidosis, cryptococcosis, fusariosis, mucormycosis, [SDV]Life Sciences [q-bio], Treatment outcome, Medizin, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], 030207 dermatology & venereal diseases, 0302 clinical medicine, Medicine, Registries, Referral and Consultation, media_common, Aspergillus species, Infectious Disease Medicine, Guideline adherence, Disease Management, General Medicine, 3. Good health, Outreach, [SDV] Life Sciences [q-bio], Europe, Infectious Diseases, Treatment Outcome, Guideline Adherence, Life Sciences & Biomedicine, medicine.medical_specialty, Medical mycology, media_common.quotation_subject, 030106 microbiology, Azole resistance, Dermatology, Mycology, 03 medical and health sciences, Excellence, Humans, Science & Technology, business.industry, Expert consultation, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Mycoses, Family medicine, business, Invasive Fungal Infections
Abstract: Contains fulltext : 220076.pdf (Publisher’s version ) (Open Access) OBJECTIVES: Difficult-to-treat invasive fungal infections require infectious diseases expert consultation to improve treatment outcome and increase survival rates. METHODS: The European Confederation of Medical Mycology (ECMM) intends to provide expert help free of charge by a newly founded ECMM Expert Consultation Service for medical centres around the globe seeking advice when there is no fungal infection consultant available. The expert consult will provide recommendations and broad expertise on difficult-to-treat invasive fungal infections (eg azole-resistant Aspergillus species, Candida auris, mucormycosis) to improve diagnostic and therapeutic management and outcome. RESULTS: The initiative plans global outreach through video conferencing between ECMM Excellence Centers and treating physicians. FungiScope((R)) registries will be used to structure case information and to evaluate the impact of the collegial advice system at regular intervals. Advice will follow recent guidelines, and EQUAL Scores will be used to measure guideline adherence. CONCLUSIONS: Infectious diseases expert consultation should be an integral component of care for patients with difficult-to-treat invasive fungal infections. The ECMM Expert Consult will attend to this matter on a global scale.
Published: 2020
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43. Early-infantile onset epilepsy and developmental delay caused by bi-allelic GAD1 variants

Author: Neuray, C., Maroofian, R., Scala, M., Sultan, T., Pai, G. S., Mojarrad, M., Khashab, H. E., Deholl, L., Yue, W., Alsaif, H. S., Zanetti, M. N., Bello, O., Person, R., Eslahi, A., Khazaei, Z., Feizabadi, M. H., Efthymiou, S., El-Bassyouni, H. T., Soliman, D. R., Tekes, S., Ozer, L., Baltaci, V., Khan, S., Beetz, C., Amr, K. S., Salpietro, V., Jamshidi, Y., Alkuraya, F. S., Houlden, H., Groppa, S., Karashova, B. M., Nachbauer, W., Boesch, S., Arning, L., Timmann, D., Cormand, B., Perez-Duenas, B., Synaps, Group, Di Rosa, G., Aguennouz, M., Goraya, J. S., Mine, J., Avdjieva, D., Kathom, H., Tincheva, R., Banu, S., Pineda-Marfa, M., Veggiotti, P., Ferrari, M. D., Verrotti, A., Marseglia, G., Savasta, S., Garcia-Silva, M., Ruiz, A. M., Garavaglia, B., Borgione, E., Portaro, S., Sanchez, B. M., Boles, R., Papacostas, S., Vikelis, M., Papanicolaou, E. Z., Dardiotis, E., Maqbool, S., Ibrahim, S., Kirmani, S., Rana, N. N., Atawneh, O., Koutsis, G., Breza, M., Mangano, S., Scuderi, C., Morello, G., Stojkovic, T., Zollo, M., Heimer, G., Dauvilliers, Y. A., Striano, P., Al-Khawaja, I., Al-Mutairi, F., Sherifa, H., Neuray C., Maroofian R., Scala M., Sultan T., Pai G.S., Mojarrad M., Khashab H.E., deHoll L., Yue W., Alsaif H.S., Zanetti M.N., Bello O., Person R., Eslahi A., Khazaei Z., Feizabadi M.H., Efthymiou S., El-Bassyouni H.T., Soliman D.R., Tekes S., Ozer L., Baltaci V., Khan S., Beetz C., Amr K.S., Salpietro V., Jamshidi Y., Alkuraya F.S., Houlden H., Mangano S., Dicle Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Tıbbi Biyoloji Ana Bilim Dalı, Tekeş, Selahattin, University College of London [London] (UCL), Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), University of Genoa (UNIGE), IRCCS Istituto Giannina Gaslini [Genoa, Italy], Children's Hospital [Lahore], Institute of Child Health [Lahore], Medical University of South Carolina [Charleston] (MUSC), Mashhad University of Medical Sciences, Ain Shams University (ASU), University of Oxford [Oxford], GeneDx [Gaithersburg, MD, USA], Khorasan Razavi Agricultural and Natural Resources Research and Education Center, National Research Centre [Cairo, Egypt], Benha University (BU), Dicle University, CENTOGENE AG, University of London [London], King Faisal Specialist Hospital [Riyadh, Saudi Arabia] (Research Centre), and SYNaPS Study Group: Stanislav Groppa, Blagovesta Marinova Karashova, Wolfgang Nachbauer, Sylvia Boesch, Larissa Arning, Dagmar Timmann, Bru Cormand, Belen Pérez-Dueñas, Gabriella Di Rosa, Jatinder S Goraya, Tipu Sultan, Jun Mine, Daniela Avdjieva, Hadil Kathom, Radka Tincheva, Selina Banu, Mercedes Pineda-Marfa, Pierangelo Veggiotti, Michel D Ferrari, Alberto Verrotti, Giangluigi Marseglia, Salvatore Savasta, Mayte García-Silva, Alfons Macaya Ruiz, Barbara Garavaglia, Eugenia Borgione, Simona Portaro, Benigno Monteagudo Sanchez, Richard Boles, Savvas Papacostas, Michail Vikelis, Eleni Zamba Papanicolaou, Efthymios Dardiotis, Shazia Maqbool, Shahnaz Ibrahim, Salman Kirmani, Nuzhat Noureen Rana, Osama Atawneh, George Koutsis, Marianthi Breza, Salvatore Mangano, Carmela Scuderi, Eugenia Borgione, Giovanna Morello, Tanya Stojkovic, Massimi Zollo, Gali Heimer, Yves A Dauvilliers, Pasquale Striano, Issam Al-Khawaja, Fuad Al-Mutairi, Hamed Sherifa
Subjects: Male, 0301 basic medicine, Glutamate decarboxylase, Malalties cerebrals, Neurotransmissors, Neurodevelopmental delay, Epilepsy, 0302 clinical medicine, MESH: Child, Age of Onset, Child, cleft palate, GAD1, AcademicSubjects/SCI01870, Glutamate Decarboxylase, Glutamate receptor, Muscle weakness, purl.org/becyt/ford/3.1 [https], Neurotransmitters, MESH: Infant, Hypotonia, muscle weakne, Cleft palate, MESH: Epilepsy, Child, Preschool, Muscle Hypotonia, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], purl.org/becyt/ford/3 [https], Female, Brain diseases, Abnormalities, medicine.symptom, Multiple, medicine.drug, epilepsy, muscle weakness, neurodevelopmental delay, MESH: Glutamate Decarboxylase, medicine.medical_specialty, MESH: Abnormalities, Multiple, MESH: Mutation, MESH: Age of Onset, Biology, Inhibitory postsynaptic potential, GAD1, cleft palate, epilepsy, muscle weakness, neurodevelopmental delay, gamma-Aminobutyric acid, 03 medical and health sciences, Excitatory synapse, Internal medicine, medicine, Humans, Abnormalities, Multiple, Preschool, Alleles, MESH: Neurodevelopmental Disorders, MESH: Humans, MESH: Muscle Hypotonia, MESH: Alleles, MESH: Child, Preschool, Infant, medicine.disease, MESH: Male, Epilèpsia, Editor's Choice, 030104 developmental biology, Endocrinology, Neurodevelopmental Disorders, Mutation, AcademicSubjects/MED00310, Neurology (clinical), MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery, Reports
Abstract: Mice lacking GAD1 show neonatal mortality, but the human phenotype associated with GAD1 disruption is poorly characterized. Neuray et al. describe six patients with biallelic GAD1 mutations, presenting with early-infantile onset epilepsy, neurodevelopmental delay, muscle weakness and non-CNS manifestations., Gamma-aminobutyric acid (GABA) and glutamate are the most abundant amino acid neurotransmitters in the brain. GABA, an inhibitory neurotransmitter, is synthesized by glutamic acid decarboxylase (GAD). Its predominant isoform GAD67, contributes up to ∼90% of base-level GABA in the CNS, and is encoded by the GAD1 gene. Disruption of GAD1 results in an imbalance of inhibitory and excitatory neurotransmitters, and as Gad1−/− mice die neonatally of severe cleft palate, it has not been possible to determine any potential neurological dysfunction. Furthermore, little is known about the consequence of GAD1 disruption in humans. Here we present six affected individuals from six unrelated families, carrying bi-allelic GAD1 variants, presenting with developmental and epileptic encephalopathy, characterized by early-infantile onset epilepsy and hypotonia with additional variable non-CNS manifestations such as skeletal abnormalities, dysmorphic features and cleft palate. Our findings highlight an important role for GAD1 in seizure induction, neuronal and extraneuronal development, and introduce GAD1 as a new gene associated with developmental and epileptic encephalopathy.
Published: 2020
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44. Bi-allelic HPDL Variants Cause a Neurodegenerative Disease Ranging from Neonatal Encephalopathy to Adolescent-Onset Spastic Paraplegia

Author: Andrea Bevot, Diana Chiang, Laurence Colleaux, Christian A. Hübner, Hans Hartmann, Zhao-Qi Wang, Tobias B. Haack, Ralf A. Husain, J. Christopher Hennings, Kevin Rostasy, Michael C. Kruer, Hossein Darvish, Olaf Riess, Andy Cheuk Him Ng, Marion Döbler-Neumann, Tim M. Strom, Lucia Laugwitz, Johannes A. Mayr, Thomas Klopstock, Xenia Kobeleva, René G. Feichtinger, Saghar Ghasemi Firouzabadi, Rebecca Buchert, Amelie J. Müller, Matias Wagner, Antje K. Huebner, Shrikant Mane, Marcus Deschauer, Ingeborg Krägeloh-Mann, Abdelkrim Saadi, Ulrich Brandl, Penelope E. Bonnen, Christian Marx, Isabell Cordts, Thomas Klockgether, Abbas Tafakhori, Thomas Meitinger, Florentine Radelfahr, Arnaud Besse, Mona Grimmel, Marc Sturm, Saskia B. Wortmann, Somayeh Bakhtiari, Francois V. Bolduc, Stefanie Beck-Woedl, Thomas Nägele, Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Jena University Hospital [Jena], University of Tübingen, Helmholtz-Zentrum München (HZM), Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Leibniz Association, Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Université d'Alger 1 (Benyoucef Benkhedda), Universität Witten Herdecke, German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), University Children's Hospital of Tübingen, Partenaires INRAE, Hannover Medical School [Hannover] (MHH), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Technische Universität München [München] (TUM), University of Bonn, Semnan University, University of Arizona, Baylor College of Medicine (BCM), Baylor University, University of Alberta, Tehran University of Medical Sciences (TUMS), Yale University School of Medicine, University of Social Welfare and Rehabilitation Sciences [Tehran], Universitätsklinikum Tübingen - University Hospital of Tübingen, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], Munich Cluster for systems neurology [Munich] (SyNergy), Technische Universität München [München] (TUM)-Ludwig-Maximilians-Universität München (LMU), Amalia Children’s Hospital [Nijmegen, The Netherlands], Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig-Maximilians-Universität München (LMU), Helmholtz Zentrum München = German Research Center for Environmental Health, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Yale School of Medicine [New Haven, Connecticut] (YSM), and COLLEAUX, Laurence
Subjects: 0301 basic medicine, Male, mitochondrial metabolism, Neurological disorder, Mitochondrion, 0302 clinical medicine, Spastic, Child, Genetics (clinical), Exome sequencing, ComputingMilieux_MISCELLANEOUS, Brain Diseases, genetics [Brain Diseases], Neurodegenerative Diseases, encephalopathy, Mitochondria, 3. Good health, Pedigree, developmental delay, Phenotype, Female, genetics [Mitochondrial Proteins], movement disorder, medicine.symptom, Adult, Adolescent, Hereditary spastic paraplegia, Encephalopathy, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Developmental Delay, Exome Sequencing, Hereditary Spastic Paraplegia, Hpdl, Leigh-like Syndrome, Mitochondrial Metabolism, Movement Disorder, Mitochondrial Proteins, Leigh-like syndrome, 03 medical and health sciences, Young Adult, Report, ddc:570, genetics [Spastic Paraplegia, Hereditary], Genetics, medicine, Humans, Spasticity, Amino Acid Sequence, hereditary spastic paraplegia, Allele, Alleles, Spastic Paraplegia, Hereditary, business.industry, HPDL, medicine.disease, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, genetics [Neurodegenerative Diseases], Immunology, genetics [Mitochondria], business, exome sequencing, 030217 neurology & neurosurgery
Abstract: International audience; We report bi-allelic pathogenic HPDL variants as a cause of a progressive, pediatric-onset spastic movement disorder with variable clinical presentation. The single-exon gene HPDL encodes a protein of unknown function with sequence similarity to 4-hydroxyphenylpyruvate dioxygenase. Exome sequencing studies in 13 families revealed bi-allelic HPDL variants in each of the 17 individuals affected with this clinically heterogeneous autosomal-recessive neurological disorder. HPDL levels were significantly reduced in fibroblast cell lines derived from more severely affected individuals, indicating the identified HPDL variants resulted in the loss of HPDL protein. Clinical presentation ranged from severe, neonatal-onset neurodevelopmental delay with neuroimaging findings resembling mitochondrial encephalopathy to milder manifestation of adolescent-onset, isolated hereditary spastic paraplegia. All affected individuals developed spasticity predominantly of the lower limbs over the course of the disease. We demonstrated through bioinformatic and cellular studies that HPDL has a mitochondrial localization signal and consequently localizes to mitochondria suggesting a putative role in mitochondrial metabolism. Taken together, these genetic, bioinformatic, and functional studies demonstrate HPDL is a mitochondrial protein, the loss of which causes a clinically variable form of pediatric-onset spastic movement disorder.
Published: 2020
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45. Brief recommendations for participation in leisure time or competitive sports in athletes-patients with coronary artery disease: Summary of a Position Statement from the Sports Cardiology Section of the European Association of Preventive Cardiology (EAPC)

Author: Hanne Rasmusen, Michael Papadakis, Martin Halle, Christian Schmied, Andre LaGerche, Josef Niebauer, Antonio Pelliccia, Alessandro Biffi, François Carré, Axel Pressler, Mikael Dellborg, Luis Serratosa, Paolo Emilio Adami, Erik Ekker Solberg, Stefano Caselli, Mats Börjesson, Frank van Buuren, Sanjay Sharma, University of Gothenburg (GU), Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, medicine.medical_specialty, Competitive Behavior, Consensus, Epidemiology, Coronary Vessel Anomalies, Leisure time, MEDLINE, Cardiology, Coronary Artery Disease, 030204 cardiovascular system & hematology, sports participation, Risk Assessment, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, 030212 general & internal medicine, Healthy Lifestyle, Vascular Diseases, Adverse effect, Association (psychology), biology, business.industry, Athletes, medicine.disease, biology.organism_classification, 3. Good health, Coronary arteries, Preventive cardiology, medicine.anatomical_structure, Heart Disease Risk Factors, recommendations, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Female, Cardiology and Cardiovascular Medicine, business, Risk Reduction Behavior, Sports
Abstract: This paper presents a brief summary of the recommendations from the Sports Cardiology section of the European Association of Preventive Cardiology (EAPC) on sports-participation in patients with coronary artery disease, coronary artery anomalies or spontaneous dissection of the coronary arteries, all entities being associated with myocardial ischaemia.1 Given the wealth of evidence supporting the benefits of exercise for primary and secondary prevention of coronary artery disease, individuals should be restricted from competitive sport only when a substantial risk of adverse event or disease progression is present. These recommendations aim to encourage regular physical activity including participation in sports and, with reasonable precaution, ensure a high level of safety for all individuals with coronary artery disease. The present document is based on available current evidence, but in most instances because of lack of evidence, also on clinical experience and expert opinion.
Published: 2019
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46. Periprocedural Heparin During Endovascular Treatment of Tandem Lesions in Patients with Acute Ischemic Stroke: A Propensity Score Analysis from TITAN Registry

Author: François, Zhu, Michel, Piotin, Henrik, Steglich-Arnholm, Julien, Labreuche, Markus, Holtmannspötter, Christian, Taschner, Sebastian, Eiden, Diogo C, Haussen, Raul G, Nogueira, Panagiotis, Papanagiotou, Maria, Boutchakova, Adnan H, Siddiqui, Bertrand, Lapergue, Franziska, Dorn, Christophe, Cognard, Monika, Killer-Oberpfalzer, Salvatore, Mangiafico, Marc, Ribo, Marios N, Psychogios, Alejandro, Spiotta, Mohammad, Anadani, Marc-Antoine, Labeyrie, Mikael, Mazighi, Alessandra, Biondi, Sébastien, Richard, René, Anxionnat, Serge, Bracard, Francis, Turjman, Benjamin, Gory, Jean-Christophe, Lacour, Département de neuroradiologie diagnostique et thérapeutique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Hôpital Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Rigshospitalet [Copenhagen], Copenhagen University Hospital, Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Freiburg University Medical Center, Emory University School of Medicine, Emory University [Atlanta, GA], Klinikum Bremen-Mitte, University at Buffalo [SUNY] (SUNY Buffalo), State University of New York (SUNY), Hôpital Foch [Suresnes], University-Hospital Munich-Großhadern [München], Service de neuroradiologie [CHU Toulouse], CHU Toulouse [Toulouse], Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Careggi University Hospital, Vall d'Hebron University Hospital [Barcelona], University Medical Center Göttingen (UMG), Medical University of South Carolina [Charleston] (MUSC), Service de Neuroradiologie [CHU Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Service de Neuroradiologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), 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 neurologie [CHRU Nancy], Hospices Civils de Lyon (HCL), CHU Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Universitäts Klinikum Freiburg = University Medical Center Freiburg (Uniklinik), Pôle Cardiovasculaire et Métabolique [CHU Toulouse], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: Male, medicine.medical_specialty, Time Factors, Endovascular Treatment, Brain Ischemia, 030218 nuclear medicine & medical imaging, Tandem occlusion, 03 medical and health sciences, Anticoagulation, 0302 clinical medicine, Modified Rankin Scale, Occlusion, medicine, Humans, Radiology, Nuclear Medicine and imaging, Prospective Studies, Registries, Propensity Score, Stroke, Acute ischemic stroke, Retrospective Studies, Thrombectomy, business.industry, Heparin, Endovascular Procedures, Anticoagulants, Middle Aged, medicine.disease, Combined Modality Therapy, 3. Good health, Surgery, Treatment Outcome, Propensity score matching, Cohort, Female, Observational study, Cardiology and Cardiovascular Medicine, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: International audience; Background and purpose: Data on safety and efficacy of periprocedural use of heparin are limited during treatment of acute ischemic stroke patients with anterior circulation tandem occlusion. This study aimed to investigate the impact of heparin use during endovascular therapy of anterior circulation tandem occlusions on the functional and safety outcomes.Methods: A retrospective analysis of the multicenter observational TITAN registry was performed. Patients with anterior circulation tandem occlusion and treated with endovascular therapy (EVT) were included, with or without extracranial carotid intervention. We divided patients into two groups based on periprocedural heparin use (heparin vs. non-heparin). The dose of intravenous unfractionated heparin ranged from 1500 to 2500 I.U. Primary study endpoint was 90-day Modified Rankin Scale (mRS). Secondary study endpoint included angiographic and safety endpoints such as hemorrhagic complications. A propensity-score-matched analysis was performed.Results: Among 369 patients, heparin was used in 68 patients (18.4%). In the propensity-score-matched cohort, favorable outcome (mRS 0-2) occurred in 51.3% in heparin group and 58.0% in non-heparin group (matched OR, 0.76; 95% CI, 0.32-1.78; P = 0.52). Similar result was found in propensity-score-adjusted cohort (adjusted OR, 0.72; 95%CI, 0.39-1.32; P = 0.28). Likewise, there was no difference in the rate of successful reperfusion (mTICI 2b-3) (propensity-score-adjusted OR, 1.03; 95%CI, 0.50-2.09; P = 0.93) neither in safety endpoints between the two groups.Conclusions: Periprocedural heparin use during EVT of anterior circulation tandem occlusions was not associated with better functional, angiographic or safety outcomes. These findings are applicable for low doses of heparin, and further studies are warranted.
Published: 2019
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47. Acute thromboses and occlusions of dual layer carotid stents in endovascular treatment of tandem occlusions

Author: Erasmia Broussalis, Michel Piotin, Martin Bendszus, Ansgar Berlis, Hendrik Janssen, Fritz Wodarg, Frank Runck, Raphaël Blanc, Johannes Hensler, Christoph Maurer, Vincent Costalat, Markus A Möhlenbruch, Cyril Dargazanli, Monika Killer-Oberpfalzer, Johannes Pfaff, Heidelberg University Hospital [Heidelberg], University of Augsburg [Augsburg], University of Salzburg, Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Klinikum Nürnberg Nord, Klinikum Ingolstadt, Hôpital Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de Neuroradiologie[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Universität Augsburg [Augsburg], University Medical Center of Schleswig–Holstein = Universitätsklinikum Schleswig-Holstein (UKSH), and Kiel University
Subjects: Carotid Artery Diseases, Male, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, medicine.medical_treatment, 030204 cardiovascular system & hematology, 0302 clinical medicine, MESH: Risk Factors, Risk Factors, Occlusion, Stent, Stroke, Thrombectomy, MESH: Treatment Outcome, MESH: Aged, MESH: Middle Aged, Endovascular Procedures, General Medicine, Middle Aged, Thrombosis, 3. Good health, Europe, Treatment Outcome, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, Stents, Internal carotid artery, Carotid Artery, Internal, medicine.medical_specialty, MESH: Carotid Artery, Internal, MESH: Endovascular Procedures, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, 03 medical and health sciences, medicine.artery, medicine, Humans, MESH: Thrombosis, ddc:610, cardiovascular diseases, Thrombus, Aged, Retrospective Studies, MESH: Humans, MESH: Carotid Artery Diseases, business.industry, MESH: Retrospective Studies, medicine.disease, MESH: Male, Surgery, MESH: Stents, Stenosis, Carotid artery occlusion, MESH: Europe, Neurology (clinical), business, MESH: Female, 030217 neurology & neurosurgery
Abstract: PurposeTo evaluate the occurrence and risk factors of acute in-stent thrombosis or stent occlusion in patients with tandem occlusions receiving intracranial mechanical thrombectomy and emergent extracranial internal carotid artery stenting with a dual layer carotid stent.MethodsMulticenter retrospective data collection and analysis of stroke databases of seven comprehensive stroke centers from three European countries.ResultsOverall, 160 patients (mean (SD) age 66 (12) years; 104 men (65%); median (IQR) baseline NIHSS 14 (9–18); IV lysis, n=97 (60.6%)) were treated for a cervical carotid artery occlusion or stenosis using a CASPER stent (MicroVention), and received mechanical thrombectomy for an intracranial occlusion between April 2014 and November 2018. During the procedure or within 72 hours, formation of thrombus and complete occlusion of the CASPER stent was observed in 33/160 (20.8%) and in 12/160 patients (7.5%), respectively. In 25/33 (75.8%) and in 9/12 patients (75%), respectively, this occurred during the procedure. No statistically significant difference was observed between patients with and without thrombus formation with regard to pre-existing long term medication with anticoagulants or intraprocedural administration of heparin, acetylsalicylic acid (ASA), or heparin and ASA. Favorable early neurological outcome was similar in patients with (n=15; 45.5%) and without (n=63; 49.6%) thrombus formation at the CASPER stent.ConclusionAcute thrombosis or occlusion of CASPER stents in thrombectomy patients receiving emergent extracranial internal carotid artery stenting for tandem occlusions were observed more often during the procedure than within 72 hours of follow-up, were less frequent then previously reported, and showed no impact on early neurological outcome.
Published: 2019
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48. Abstract WP10: Impact of Prior Intravenous Thrombolysis on the Outcome of Emergent Carotid Stenting in Acute Stroke Patients With Tandem Occlusion: A Collaborative Pooled Analysis

Author: René Anxionnat, Sebastian Eiden, Salvatore Mangiafico, Marc Ribó, Diogo C Haussen, Benjamin Gory, Marc A Labeyrie, Monika Killer, Franziska Dorn, Bertrand Lapergue, Mohammad Anadani, Henrik Steglich-Arnholm, Marios Psychogios, Alejandro M Spiotta, Biondi Alessandra, Markus Holtmannspötter, Serge Bracard, Sébastien Richard, Christian Taschner, Michel Piotin, Mikael Mazighi, Christophe Cognard, Raul G Nogueira, Panagiotis Papanagiotou, Francis Turjman, Maria Boutchakova, Steven Lauzon, Adnan H. Siddiqui, Medical University of South Carolina [Charleston] (MUSC), Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hospices Civils de Lyon (HCL), Rigshospitalet [Copenhagen], Copenhagen University Hospital, Freiburg University Medical Center, Emory University School of Medicine, Emory University [Atlanta, GA], Klinikum Bremen-Mitte, University at Buffalo [SUNY] (SUNY Buffalo), State University of New York (SUNY), Hôpital Foch [Suresnes], Klinikum der Universität [München], Neuroradiologie Diagnostique et Thérapeutique [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Azienda Ospedaliero-Universitaria Careggi (AOU Careggi), Vall d'Hebron University Hospital [Barcelona], University Medical Center Göttingen (UMG), Service de Neuroradiologie [CHU Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Département de neuroradiologie diagnostique et thérapeutique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), and Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: medicine.medical_specialty, medicine.medical_treatment, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Occlusion, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Stroke, ComputingMilieux_MISCELLANEOUS, Acute stroke, Advanced and Specialized Nursing, business.industry, Stent, Thrombolysis, medicine.disease, Pooled analysis, Cardiology, Neurology (clinical), Carotid stenting, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background: Acute tandem occlusion (ATO) management is technically challenging and was not sufficiently evaluated in trials. There is evidence suggesting the efficacy and safety of emergent carotid stenting in conjunction with mechanical thrombectomy (MT) for ATO treatment. However, the safety of carotid stenting (CS) post intravenous tPA (IVT) treatment remains unclear. Objective: to report the safety and functional outcomes of emergent CS post IVT, and compare it to non-IVT patients. Methods: This was a retrospective multicenter international TITAN collaboration including 18 endovascular databases. In the present analysis, patients were included if they presented with acute ischemic stroke (AIS) due to ATO and were treated with CS in conjunction with MT. ATO was defined as an extracranial internal carotid artery (ICA) lesion (complete occlusion or stenosis >=90%) and an intracranial proximal occlusion (distal ICA and/or first or second segment of the middle cerebral artery). Outcome measures included final mTICI score, 90 day-modified Rankin Scale (mRS), mortality, procedural complications, and symptomatic intracerebral hemorrhage. Mixed effects logistic model was used to determine the predictors of each outcome Results: Among 454 patients with ATO, 289 were treated with CS and included in the present analysis. One hundred seventy-five patients (60%) of the included patients received IVT prior to MT. Onset to groin was shorter in the IVT group (259 ±251 vs. 353±238; p=0.013). Otherwise, there was no difference in baseline characteristics between the two groups. Heparin use during procedure was less in IVT group (20% vs. 54%; p Conclusion: Emergent CS in association with MT after IVT was safe and was not associated with an increased risk of sICH or procedural complications.
Published: 2019
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49. Abstract TP29: Complete Occlusion is Associated With Lower Recanalization Rate in Patients With Acute Stroke With Tandem Lesion Treated With Thrombectomy

Author: Mikael Mazighi, Serge Bracard, Diogo C Haussen, Panagiotis Papanagiotou, Franziska Dorn, Marios Psychogios, Bertrand Lapergue, Monika Killer, Marc Ribó, Christophe Cognard, Christian Taschner, Mohammad Anadani, Michel Piotin, Alessandra Biondi, Adnan H. Siddiqui, Markus Holtmannspötter, Francis Turjman, Henrik Steglich-Arnholm, Sébastien Richard, Raul G Nogueira, Benjamin Gory, Sebastian Eiden, René Anxionnat, Salvatore Mangiafico, Marc A Labeyrie, Alejandro M Spiotta, Maria Boutchakova, Medical University of South Carolina [Charleston] (MUSC), Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hospices Civils de Lyon (HCL), Rigshospitalet [Copenhagen], Copenhagen University Hospital, Freiburg University Medical Center, Emory University School of Medicine, Emory University [Atlanta, GA], Klinikum Bremen-Mitte, University at Buffalo [SUNY] (SUNY Buffalo), State University of New York (SUNY), Hôpital Foch [Suresnes], Klinikum der Universität [München], CHU Toulouse [Toulouse], Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Azienda Ospedaliero-Universitaria Careggi (AOU Careggi), Vall d'Hebron University Hospital [Barcelona], University Medical Center Göttingen (UMG), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)
Subjects: Advanced and Specialized Nursing, medicine.medical_specialty, business.industry, medicine.medical_treatment, Thrombolysis, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, medicine.disease, Lesion, medicine.artery, Internal medicine, Complete occlusion, Occlusion, Cardiology, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Medicine, In patient, Neurology (clinical), Internal carotid artery, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Stroke, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Acute stroke
Abstract: Introduction: Previous studies showed that mechanical thrombectomy (MT) is safe and effective in tandem steno-occlusive lesion. The effect on initial tandem extracranial internal carotid artery (ICA) lesion severity on outcome is unknown. In this study, we aimed to compare angiographic, functional and hemorrhagic outcomes according to initial lesion severity Methods: A multicenter international retrospective study that included 18 stroke centers. Patients were included if they presented with ischemic stroke due to tandem lesion and were treated with MT with or without carotid stenting. Tandem lesion was defined as proximal intracranial occlusion (distal ICA, M1/M2) and extracranial internal carotid artery (ICA) occlusion or ≥90% stenosis NASCET. We divided patients into two groups based on extracranial ICA lesion severity (severe stenosis vs. complete occlusion) at the first angiographic run. Outcome measures included 90 day mRS, final mTICI score, procedural complications and symptomatic hemorrhage. Symptomatic hemorrhage (Sich) was defined based on ECASS criteria. Results: A total of 305 patients were included in the present analysis. 134 patients had complete ICA occlusion (group 1) ,and 170 had ≥90% ICA stenosis (group 2). Hyperlipidemia was more frequent in group 1 ((46.5% vs. 33.6%, p=0.032), and diabetes was less frequent (12.4 vs. 23.8%;p=0.011). Otherwise there was no significant difference in baseline characteristics, pretreatment tPA , and ASPECTS between two groups. With respect to outcome, successful recanalization (TICI 2b-3) was lower in group 1 than group 2 (70% vs. 80%; p=0.038). Similarly TICI 3 was achieved in less patients in group 1 (24% vs. 40%;p=0.022). Favorable outcome (mRS 0-2), sICH and procedural complications were similar in both groups. Conclusion: Initial angiographic severity of extracranial ICA lesion in tandem occlusions was associated with lower recanalization rates after MT, without impact on clinical outcomes.
Published: 2019
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50. Recommendations for participation in leisure time or competitive sports in athletes-patients with coronary artery disease a position statement from the Sports Cardiology Section of the European Association of Preventive Cardiology (EAPC)

Author: Mats Borjesson, Mikael Dellborg, Josef Niebauer, Andre LaGerche, Christian Schmied, Erik E Solberg, Martin Halle, Emilio Adami, Alessandro Biffi, Francois Carré, Stefano Caselli, Michael Papadakis, Axel Pressler, Hanne Rasmusen, Luis Serratosa, Sanjay Sharma, Frank van Buuren, Antonio Pelliccia, University of Gothenburg (GU), Sahlgrenska University Hospital/Östra, Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Baker Heart and Diabetes Institute (AUSTRALIA), Diakonhjemmet Hospital, Hôpital Lapeyronie [Montpellier] (CHU), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
Subjects: 03 medical and health sciences, Leisure Activities, 0302 clinical medicine, Humans, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Coronary Artery Disease, 030212 general & internal medicine, 030204 cardiovascular system & hematology, Cardiology and Cardiovascular Medicine, ComputingMilieux_MISCELLANEOUS, Sports, 3. Good health
Abstract: International audience
Published: 2019
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