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151. Human milk fatty acid composition and its association with maternal blood and adipose tissue fatty acid content in a cohort of women from Europe

Author: Francesca Giuffrida, Mathilde Fleith, Amélie Goyer, Tinu Mary Samuel, Isabelle Elmelegy-Masserey, Patric Fontannaz, Cristina Cruz-Hernandez, Sagar K. Thakkar, Cathriona Monnard, Carlos Antonio De Castro, Luca Lavalle, Thameur Rakza, Massimo Agosti, Isam Al-Jashi, Almerinda Barroso Pereira, Maria Jose Costeira, Giovanna Marchini, Mireille Vanpee, Tom Stiris, Sylvia Stoicescu, Maria Gorett Silva, Jean-Charles Picaud, Cecilia Martinez-Costa, Magnus Domellöf, Claude Billeaud, Nestlé Research Center | Centre de recherche Nestlé [Lausanne], Nestlé S.A., SBU Nutrition [Vevey, Switzerland] (Nestlé ), Nestlé Research [Singapore] (NRS), Centre d'Investigation Clinique - Innovation Technologique de Lille - CIC 1403 - CIC 9301 (CIC Lille), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Ospedale del Ponte [Varese, Italy], Al Jashi Isam Private Med. Practice [Bucharest, Romania], Hospital de São Marcos [Braga, Portugal] (HSM), Life and Health Sciences Research Institute [Braga] (ICVS), University of Minho [Braga], Karolinska University Hospital [Stockholm], Oslo University Hospital [Oslo], Polizu Hospital [Bucharest, Romania], Hospital de S. João [Porto, Portugal] (HSJ), 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), Universitat de València (UV), Umeå University, CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), and CarMeN, laboratoire
Subjects: Erythrocytes, Docosahexaenoic Acids, [SDV]Life Sciences [q-bio], Medicine (miscellaneous), Adipose tissue, Linoleic Acid, Plasma, Pregnancy, Humans, Lactation, Fatty acids, LCPUFA, Nutrition, Nutrition and Dietetics, Arachidonic Acid, Milk, Human, Human milk, food and beverages, Infant, Lipids, Näringslära, [SDV] Life Sciences [q-bio], DHA, Breast Feeding, Fatty Acids, Unsaturated, lipids (amino acids, peptides, and proteins), Female
Abstract: PurposeHuman milk (HM) composition is influenced by factors, like maternal diet and body stores, among other factors. For evaluating the influence of maternal fatty acid (FA) status on milk FA composition, the correlation between FA content in HM and in maternal plasma, erythrocytes, and adipose tissue was investigated.Methods223 European women who delivered at term, provided HM samples over first four months of lactation. Venous blood and adipose tissue (only from mothers who consented and underwent a C-section delivery) were sampled at delivery. FAs were assessed in plasma, erythrocytes, adipose tissue, and HM. Evolution of HM FAs over lactation and correlations between FA content in milk and tissues and between mother’s blood and cord blood were established.ResultsDuring lactation, arachidonic acid (ARA) and docosahexaenoic acid (DHA) significantly decreased, while linoleic acid (LA), alpha-linolenic acid (ALA), and eicosapentaenoic acid (EPA) remained stable. Positive correlations were observed between HM and adipose tissue for palmitic, stearic, oleic, and polyunsaturated fatty acids (PUFAs). Correlations were found between milk and plasma for oleic, LA, ARA, ALA, DHA, monounsaturated fatty acids (MUFAs), and PUFAs. No correlation was observed between erythrocytes and HM FAs. LA and ALA were more concentrated in maternal blood than in infant blood, contrary to ARA and DHA, supporting that biomagnification of LCPUFAs may have occurred during pregnancy.ConclusionsThese data show that maternal adipose tissue rather than erythrocytes may serve as reservoir of PUFAs and LCPUFAs for human milk. Plasma also supplies PUFAs and LCPUFAs to maternal milk. If both, adipose tissue and plasma PUFAs, are reflection of dietary intake, it is necessary to provide PUFAs and LCPUFAs during pregnancy or even before conception and lactation to ensure availability for mothers and enough supply for the infant via HM.
Published: 2022

152. Cerebral Microbleeds and Treatment Effect of Intravenous Thrombolysis in Acute Stroke:An Analysis of the WAKE-UP Randomized Clinical Trial

Author: Norbert Nighoghossian, Jan Vynckier, Josep Puig, Vincent Thijs, Claus Z Simonsen, Tim Bastian Braemswig, Götz Thomalla, Märit Jensen, Florent Boutitie, Ivana Galinovic, Christian H. Nolte, Christian Gerloff, Bastian Cheng, Martin Ebinger, Keith W. Muir, Jens Fiehler, Salvador Pedraza, Robin Lemmens, Matthias Endres, Jochen B. Fiebach, Ludwig Schlemm, Wake-Up investigators, Tae-Hee Cho, CarMeN, laboratoire, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Klinik für Neurologie, Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Humboldt University Of Berlin, Berlin Institute of Health (BIH), Center for Stroke Research Berlin, Freie Universität Berlin, Hospices Civils de Lyon (HCL), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Bern University Hospital [Berne] (Inselspital), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Aarhus University Hospital, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Josep Trueta University Hospital, Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta - Girona Biomedical Research Institute (IDIBGI), University of Glasgow, German Center for Cardiovascular Research (DZHK), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), University Hospitals Leuven [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), and VIB Center for Brain & Disease Research [Leuven, Belgium]
Subjects: Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Placebo, law.invention, Fibrinolytic Agents, Randomized controlled trial, law, Modified Rankin Scale, Internal medicine, diagnostic imaging [Stroke], medicine, Humans, ddc:610, Prospective Studies, Stroke, adverse effects [Tissue Plasminogen Activator], Ischemic Stroke, Intracerebral hemorrhage, drug therapy [Cerebral Hemorrhage], business.industry, methods [Thrombolytic Therapy], Thrombolysis, Odds ratio, diagnostic imaging [Cerebral Hemorrhage], adverse effects [Thrombolytic Therapy], medicine.disease, etiology [Cerebral Hemorrhage], drug therapy [Stroke], [SDV] Life Sciences [q-bio], Treatment Outcome, Clinical research, Tissue Plasminogen Activator, Neurology (clinical), business
Abstract: Background and ObjectivesCerebral microbleeds (CMBs) are common in patients with acute ischemic stroke and are associated with increased risk of intracerebral hemorrhage (ICH) after intravenous thrombolysis. Whether CMBs modify the treatment effect of thrombolysis is unknown.MethodsWe performed a prespecified analysis of the prospective randomized controlled multicenter Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke (WAKE-UP) trial including patients with acute ischemic stroke with unknown time of symptom onset and diffusion-weighted imaging–fluid-attenuated inversion recovery mismatch on MRI receiving alteplase or placebo. Patients were screened and enrolled between September 2012 and June 2017 (with final follow-up in September 2017). Patients were randomized to treatment with IV thrombolysis with alteplase at 0.9 mg/kg body weight or placebo. CMB status (presence, number, and distribution) was assessed after study completion by 3 raters blinded to clinical information following a standardized protocol. Outcome measures were excellent functional outcome at 90 days, defined by modified Rankin Scale (mRS) score ≤1, and symptomatic ICH according to National Institutes of Neurological Disease and Stroke trial criteria 22 to 36 hours after treatment.ResultsOf 503 patients enrolled in the WAKE-UP trial, 459 (91.3%; 288 [63%] men) were available for analysis. Ninety-eight (21.4%) had at least 1 CMB on baseline imaging; 45 (9.8%) had exactly 1 CMB; 37 (8.1%) had 2 to 4 CMBs; and 16 (3.5%) had ≥5 CMBs. Presence of CMBs was associated with a nonsignificant increased risk of symptomatic ICH (11.2% vs 4.2%; adjusted odds ratio [OR] 2.32, 95% confidence interval [CI] 0.99–5.43, p = 0.052) but had no effect on functional outcome at 90 days (mRS score ≤1: 45.8% vs 50.7%; adjusted OR 0.99, 95% CI 0.59–1.64, p = 0.955). Patients receiving alteplase had better functional outcome (mRS score ≤1: 54.6% vs 44.6%, adjusted OR 1.61, 95% CI 1.07–2.43, p = 0.022) without evidence of heterogeneity in relation to CMB presence (p of the interactive term = 0.546). Results were similar for subpopulations with strictly lobar (presumed cerebral amyloid angiopathy related) or not strictly lobar CMB distribution.DiscussionIn the randomized-controlled WAKE-UP trial, we saw no evidence of reduced treatment effect of alteplase in patients with acute ischemic stroke with ≥1 CMBs. Additional studies are needed to determine the treatment effect of alteplase and its benefit-harm ratio in patients with a larger number of CMBs.Trial Registration InformationClinicalTrials.gov identifier NCT01525290; ClinicalTrialsRegister.EU identifier 2011-005906-32.Classification of EvidenceThis study provides Class II evidence that for patients with acute ischemic stroke with unknown time of onset and diffusion-weighted imaging–fluid-attenuated inversion recovery mismatch who received IV alteplase, CMBs are not significantly associated with functional outcome at 90 days.
Published: 2022

153. Recombinant human interleukin-7 reverses T cell exhaustion ex vivo in critically ill COVID-19 patients

Author: Bidar, F., Hamada, S., Gossez, M., Coudereau, R., Lopez, J., Cazalis, M. A., Tardiveau, C., Brengel-Pesce, K., Mommert, M., Buisson, M., Conti, F., Rimmele, T., Lukaszewicz, A. C., Argaud, L., Cour, M., Monneret, G., Venet, F., Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques - EA 7426 (PI3), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Centre d'Investigation Clinique [Bron] (CIC1407), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupement Hospitalier Est [Bron], Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), RICO Study Group: Remi Pescarmona, Lorna Garnier, Christine Lombard, Magali Perret, Marine Villard, Sébastien Viel, Valérie Cheynet, Elisabeth Cerrato, Estelle Peronnet, Jean-François Llitjos, Laetitia Itah, Inesse Boussaha, Françoise Poitevin-Later, Christophe Malcus, Marine Godignon, Florent Wallet, Marie-Charlotte Delignette, Frederic Dailler, Marie Simon, Auguste Dargent, Pierre-Jean Bertrand, Neven Stevic, Marion Provent, Laurie Bignet, Valérie Cerro, Jean-Christophe Richard, Laurent Bitker, Mehdi Mezidi, Loredana Baboi., CarMeN, laboratoire, Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques / Pathophysiology of Injury-induced Immunosuppression (PI3), 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), and École normale supérieure de Lyon (ENS de Lyon)
Subjects: [SDV] Life Sciences [q-bio], Exhaustion, SARS-CoV-2, Interleukin-7, [SDV]Life Sciences [q-bio], T lymphocytes, Critical Care and Intensive Care Medicine, Critically ill, Immunostimulation
Abstract: Erratum inCorrection to: Recombinant human interleukin-7 reverses T cell exhaustion ex vivo in critically ill COVID-19 patients.Bidar F, Hamada S, Gossez M, Coudereau R, Lopez J, Cazalis MA, Tardiveau C, Brengel-Pesce K, Mommert M, Buisson M, Conti F, Rimmelé T, Lukaszewicz AC, Argaud L, Cour M, Monneret G, Venet F; RICO Study Group.Ann Intensive Care. 2022 Apr 1;12(1):30. doi: 10.1186/s13613-022-01007-7.; International audience; BACKGROUND: Lymphopenia is a hallmark of severe coronavirus disease 19 (COVID-19). Similar alterations have been described in bacterial sepsis and therapeutic strategies targeting T cell function such as recombinant human interleukin 7 (rhIL-7) have been proposed in this clinical context. As COVID-19 is a viral sepsis, the objectives of this study were to characterize T lymphocyte response over time in severe COVID-19 patients and to assess the effect of ex vivo administration of rhIL-7. RESULTS: Peripheral blood mononuclear cells from COVID-19 patients hospitalized in intensive care unit (ICU) were collected at admission and after 20 days. Transcriptomic profile was evaluated through NanoString technology. Inhibitory immune checkpoints expressions were determined by flow cytometry. T lymphocyte proliferation and IFN-γ production were evaluated after ex vivo stimulation in the presence or not of rhIL-7. COVID-19 ICU patients were markedly lymphopenic at admission. Mononuclear cells presented with inhibited transcriptomic profile prevalently with impaired T cell activation pathways. CD4 + and CD8 + T cells presented with over-expression of co-inhibitory molecules PD-1, PD-L1, CTLA-4 and TIM-3. CD4 + and CD8 + T cell proliferation and IFN-γ production were markedly altered in samples collected at ICU admission. These alterations, characteristic of a T cell exhaustion state, were more pronounced at ICU admission and alleviated over time. Treatment with rhIL-7 ex vivo significantly improved both T cell proliferation and IFN-γ production in cells from COVID-19 patients. CONCLUSIONS: Severe COVID-19 patients present with features of profound T cell exhaustion upon ICU admission which can be reversed ex vivo by rhIL-7. These results reinforce our understanding of severe COVID-19 pathophysiology and opens novel therapeutic avenues to treat such critically ill patients based of immunomodulation approaches. Defining the appropriate timing for initiating such immune-adjuvant therapy in clinical setting and the pertinent markers for a careful selection of patients are now warranted to confirm the ex vivo results described so far. Trial registration ClinicalTrials.gov identifier: NCT04392401 Registered 18 May 2020, http:// clinicaltrials.gov/ct2/show/NCT04392401.
Published: 2022

154. Guidance for the diagnosis and treatment of hypolipidemia disorders

Author: Cindy Bredefeld, M. Mahmood Hussain, Maurizio Averna, Dennis D. Black, Mitchell F. Brin, John R. Burnett, Sybil Charrière, Charlotte Cuerq, Nicholas O. Davidson, Richard J. Deckelbaum, Ira J. Goldberg, Esther Granot, Robert A. Hegele, Shun Ishibashi, Wahida Karmally, Emile Levy, Philippe Moulin, Hiroaki Okazaki, Pierre Poinsot, Daniel J. Rader, Manabu Takahashi, Patrizia Tarugi, Maret G. Traber, Mathilde Di Filippo, Noel Peretti, Long Island University, Brooklyn (LIU Brooklyn), New York University Langone Medical Center (NYU Langone Medical Center), NYU System (NYU), Dipartimento Universitario di Promozione della Salute, Materno Infantile, Medicina Interna e Specialistica di Eccellenza 'G. D'Alessandro' [Palerme, Italie] (PROMISE), Università degli studi di Palermo - University of Palermo, Le Bonheur Children's Hospital [Memphis, TN, USA] (LBCH), The University of Tennessee Health Science Center [Memphis] (UTHSC), University of California [Irvine] (UC Irvine), University of California (UC), The University of Western Australia (UWA), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hospices Civils de Lyon (HCL), Washington University School of Medicine [Saint Louis, MO], Columbia University Irving Medical Center (CUIMC), New York University School of Medicine (NYU Grossman School of Medicine), Hadassah Hebrew University Medical Center [Jerusalem], Kaplan Medical Center [Rehovot, Israel], University of Western Ontario (UWO), Jichi Medical University [Tochigi-Ken, Japan], Centre de recherche du CHU Sainte-Justine / Research Center of the Sainte-Justine University Hospital [Montreal, Canada], Université de Montréal (UdeM)-CHU Sainte Justine [Montréal], The University of Tokyo (UTokyo), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), University of Pennsylvania, Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Oregon State University (OSU), and CarMeN, laboratoire
Subjects: Nutrition and Dietetics, [SDV.BA] Life Sciences [q-bio]/Animal biology, Endocrinology, Diabetes and Metabolism, Lipoproteins, Abetalipoproteinemia/diagnosis/genetics/therapy, [SDV.BA]Life Sciences [q-bio]/Animal biology, Homozygote, Chylomicron retention disease, Hypobetalipoproteinemias/diagnosis/genetics/therapy, Vitamins, Lipids, Abetalipoproteinemia, Familial hypocholesterolemia, Fat-soluble vitamins, Cholesterol, Lipid Metabolism Disorders, Internal Medicine, Humans, Cardiology and Cardiovascular Medicine, Hypobetalipoproteinemia, Triglycerides
Abstract: The Abetalipoproteinemia and Related Disorders Foundation was established in 2019 to provide guidance and support for the life-long management of inherited hypocholesterolemia disorders. Our mission is "to improve the lives of individuals and families affected by abetalipoproteinemia and related disorders". This review explains the molecular mechanisms behind the monogenic hypobetalipoproteinemia disorders and details their specific pathophysiology, clinical presentation and management throughout the lifespan. In this review, we focus on abetalipoproteinemia, homozygous hypobetalipoproteinemia and chylomicron retention disease; rare genetic conditions that manifest early in life and cause severe complications without appropriate treatment. Absent to low plasma lipid levels, in particular cholesterol and triglyceride, along with malabsorption of fat and fat-soluble vitamins are characteristic features of these diseases. We summarize the genetic basis of these disorders, provide guidance in their diagnosis and suggest treatment regimens including high dose fat-soluble vitamins as therapeutics. A section on preconception counseling and other special considerations pertaining to pregnancy is included. This information may be useful for patients, caregivers, physicians and insurance agencies involved in the management and support of affected individuals.
Published: 2022

155. ST-segment Elevation Myocardial Infarction and Primary Percutaneous Coronary Intervention: Can We Go Beyond the Clock?

Author: Gilles Rioufol, Francois Derimay, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and CarMeN, laboratoire
Subjects: Percutaneous Coronary Intervention, Treatment Outcome, myocardial infarction, [SDV.BA] Life Sciences [q-bio]/Animal biology, electrocardiography, [SDV.BA]Life Sciences [q-bio]/Animal biology, Editorials, myocardial reperfusion, Humans, ST Elevation Myocardial Infarction, Radiology, Nuclear Medicine and imaging, Cardiology and Cardiovascular Medicine, reperfusion injury
Abstract: International audience; No abstract available
Published: 2022

156. Nurse-to-Nurse Familiarity and Mortality in the Critically Ill. A Multicenter Observational Study

Author: Antoine Duclos, Cécile Payet, Loredana Baboi, Bernard Allaouchiche, Laurent Argaud, Frédéric Aubrun, Julien Bohé, Frédéric Dailler, Jean-Luc Fellahi, Jean-Jacques Lehot, Vincent Piriou, Thomas Rimmelé, Delphine Terragrossa, Stéphanie Polazzi, Claude Guérin, CarMeN, laboratoire, Université de Lyon, Pôle Information Médicale Evaluation Recherche (IMER), Hospices Civils de Lyon (HCL), Hôpital de la Croix-Rousse [CHU - HCL], Université Claude Bernard Lyon 1 (UCBL), Service d'anesthésie-réanimation [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Edouard Herriot [CHU - HCL], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Health Service and Performance Research (HESPER), Université de Lyon-Université de Lyon, HCL Groupement Hospitalier Nord [Lyon], and Service de Médecine Intensive et Réanimation [Lyon] (MIR)
Subjects: Pulmonary and Respiratory Medicine, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Staffing, Working familiarity, Nurse-to-nurse familiarity, Intensive Care Unit Organization, Critical Care and Intensive Care Medicine, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Outcome
Abstract: RATIONALE: Nurse-to-nurse familiarity at work should strengthen the components of team working and enhance its efficiency. However, its impact on patient outcomes in critical care remains poorly investigated. OBJECTIVES: To explore the role of nurse-to-nurse familiarity on inpatient deaths during intensive care unit stay. METHODS: Retrospective observational study in eight adult academic intensive care units between 01/01/2011 and 31/12/2016. MEASUREMENTS AND MAIN RESULTS: Nurse-to-nurse familiarity was measured across day and night 12-hour daily shifts as the mean number of previous collaborations between each nursing team member during previous shifts within the given Intensive Care Unit (suboptimal if\textless50). Primary outcome was a shift with at least one inpatient death, excluding death of patients with a decision to forego life-sustaining therapy. A multiple modified Poisson regression was computed to identify the determinants of mortality per shift, taking into account intensive care unit, patients' characteristics, patient-to-nurse and patient-to-assistant nurse ratios, nurse experience length and workload. A total of 43,479 patients were admitted of whom 3,311 (8%) died. Adjusted model showed a lower risk of a shift with mortality when nurse-to-nurse familiarity increased in the shift (relative risk 0.90 [0.82-0.98] 95%confidence intervals per 10 shifts, p=0.012). Low nurse-to-nurse familiarity during the shift combined with suboptimal patient-to-nurse and assistant-nurse ratios (suboptimal if \textgreater2.5 and \textgreater4, respectively) were associated with increased risk of shift with mortality (1.84 [1.15-2.96], p\textless0.001). CONCLUSIONS: Shifts with low nurse-to-nurse familiarity were associated with an increased risk of patient deaths.
Published: 2022

157. Reply: Determining Significance in a Prematurely Ceased Trial

Author: Mewton, N., Derimay, F., Motreff, P., Angoulvant, D., Rioufol, G., Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), and CarMeN, laboratoire
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract: International audience; No abstract available
Published: 2022

158. Lumasiran for Advanced Primary Hyperoxaluria Type 1: Phase 3 ILLUMINATE-C Trial

Author: Michael, M., Groothoff, J. W., Shasha-Lavsky, H., Lieske, J. C., Frishberg, Y., Simkova, E., Sellier-Leclerc, A. L., Devresse, A., Guebre-Egziabher, F., Bakkaloglu, S. A., Mourani, C., Saqan, R., Singer, R., Willey, R., Habtemariam, B., Gansner, J. M., Bhan, I., Mcgregor, T., Magen, D., Paediatric Nephrology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ARD - Amsterdam Reproduction and Development, UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - (SLuc) Service de néphrologie, CarMeN, laboratoire, Texas Children's Hospital [Houston, USA], Baylor College of Medicine (BCM), Baylor University, Emma Children’s Hospital, Amsterdam UMC - Amsterdam University Medical Center, Galilee Medical Center [Nahariya, Israel], Bar-Ilan University [Israël], Mayo Clinic [Rochester], Shaare Zedek Medical Center [Jerusalem, Israel], Al Jalila Children's Specialty Hospital, Filières Maladies Rares ORKID et ERK-Net, Centre d'Investigation Clinique [Bron] (CIC1407), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupement Hospitalier Est [Bron], Cliniques Universitaires Saint-Luc [Bruxelles], 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), Gazi University, Hôpital Hôtel Dieu de France [Beirut, Lebanon] (2HDF), Jordan University of Science and Technology [Irbid, Jordan] (JUST), Canberra Health Services [Garran, ACT, Australia] (CHS), Alnylam Pharmaceuticals [Cambridge, MA, USA], and Rambam Health Care Campus [Haifa, Israel]
Subjects: Adult, Male, RNA interference (RNAi), safety, Lumasiran, urinary oxalate (UOx), Adolescent, [SDV]Life Sciences [q-bio], kidney disease, efficacy, Young Adult, nephrocalcinosis, glycolate, pharmacodynamics, Humans, Child, Hyperoxaluria, Oxalates, systemic oxalosis, hemodialysis, cardiac dysfunction, phase 3 clinical trial, Infant, Newborn, Infant, Middle Aged, adverse events, primary hyperoxaluria type 1 (PH1), [SDV] Life Sciences [q-bio], plasma oxalate (POx), anti-drug antibodies, pediatric, Nephrology, Child, Preschool, Hyperoxaluria, Primary, Female, Kidney Diseases, pharmacokinetics
Abstract: Rationale & Objective: Lumasiran reduces urinary and plasma oxalate (POx) in patients with primary hyperoxaluria type 1 (PH1) and relatively preserved kidney function. ILLUMINATE-C evaluates the efficacy, safety, pharmacokinetics, and pharmacodynamics of lumasiran in patients with PH1 and advanced kidney disease. Study Design: Phase 3, open-label, single-arm trial. Setting & Participants: Multinational study; enrolled patients with PH1 of all ages, estimated glomerular filtration rate ≤45 mL/min/1.73 m2 (if age ≥12 months) or increased serum creatinine level (if age
Published: 2023

159. Factors Predicting Statin Initiation During Childhood in Familial Hypercholesterolemia: Importance of Genetic Diagnosis

Author: Peretti, N., Vimont, Alexandre, Mas, E., Ferrières, J., Tounian, P., Lemale, J., Boccara, F., Di Filippo, M., Charriere, S., Moulin, P., Poinsot, P., Cottin, Y., Ducluzeau, P. H., Dourmap, C., Cariou, B., Farnier, M., Paillard, F., Pradignac, A., Yelnik, C., Gallo, A., Bruckert, E., Beliard, S., 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 Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Groupement Hospitalier Lyon-Est (GHE), Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service Cardiologie [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre d'Epidémiologie et de Recherche en santé des POPulations (CERPOP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Groupe de recherche clionique Complications Cardiovasculaires et Métaboliques chez les patients vivant avec le Virus de l’immunodéficience humaine (VIH) (GRC 22 - C²MV), Hôpital Louis Pradel [CHU - HCL], Service de Cardiologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Pontchaillou [Rennes], Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de cardiologie et maladies vasculaires [Rennes] = Cardiac, Thoracic, and Vascular Surgery [Rennes], Hôpital de Hautepierre [Strasbourg], Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), 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), Service de médecine interne [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), the New French Atherosclerosis Society and the French national project CHOPIN (CHOlesterol Personalized Innovation), French Registry of Familial Hypercholesterolemia (REFERCHOL) investigators, ANR-16-RHUS-0007,CHOPIN,CHOPIN(2016), CarMeN, laboratoire, CHOPIN - - CHOPIN2016 - ANR-16-RHUS-0007 - RHUS - VALID, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Complications Cardiovasculaires et Métaboliques chez les patients vivant avec le Virus de l’immunodéficience humaine (GRC22 C²MV), Service de Cardiologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Service d'Endocrinologie, diabétologie et endocrinologie de la reproduction [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Service de Maladies infectieuses et tropicales [CHU Tenon], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université - Faculté de Médecine (SU FM), and Sorbonne Université (SU)-Service de cardiologie [CHU Tenon]
Subjects: cardiovascular risk, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, children, familial hypercholesterolemia, risk factor, treatment, Pediatrics, Perinatology and Child Health, statin, atherosclerotic cardiovascular disease, genetic, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Ldl
Abstract: International audience; OBJECTIVE: To identify childhood and parental factors associated with initiation of statin therapy in children with heterozygous familial hypercholesterolemia (HeFH), including underlying genetic diagnosis or parental premature atherosclerotic cardiovascular disease (ASCVD). STUDY DESIGN: This multicenter cohort study included 245 HeFH child-parent pairs from the REFERCHOL national register (2014-2020). Demographic and clinical characteristics at the last visit were collected. Vascular disease in parents was defined as a history of ASCVD, and/or a coronary artery calcium score \textgreater100, and/or stenosis of \textgreater50% in at least carotid artery. Statistical analyses included descriptive analysis, logistic regression for univariate and multivariate effects of statins, and a sensitivity analysis combining the characteristics of children and parents. RESULTS: Among the 245 children in the study cohort, 135 (58%), with a mean age of 14 ± 3 years, were treated with a statin. In multivariable analysis, the predictive childhood factors associated with statin treatment were genetic diagnosis (OR, 2.5; 95% CI, 1.3 to 4.9; P = .01), older age (OR, 4.4; 95% CI, 1.8-10.6; P = .01), more than 2 visits (OR, 2.36; 95% CI, 1.18-4.73; P = .015), and longer duration of follow-up (OR, 1.3; 95% CI, 1.1-1.6; P \textless .001). The predictive parental factor associated with childhood treatment was the presence of vascular disease (OR, 2.4; 95% CI, 1.0-5.7; P = .04). CONCLUSIONS: HeFH confirmed by DNA testing during childhood and a history of vascular disease in parents were independently associated with statin treatment in children with HeFH. Genetic diagnosis may be useful for cardiovascular prevention in children.
Published: 2023

160. Intracranial Hemorrhage in the TST Trial

Author: Pierre Amarenco, Jong S. Kim, Julien Labreuche, Hugo Charles, Maurice Giroud, Philippa C. Lavallée, Byung-Chul Lee, Marie-Hélène Mahagne, Elena Meseguer, Norbert Nighoghossian, Philippe Gabriel Steg, Éric Vicaut, Eric Bruckert, Pierre-Jean Touboul, Didier Leys, Yannick Béjot, Fernando Pico, Emmanuel Touzé, Gregory Ducrocq, Jérémy Abtan, Olivier Varenne, Agnes Kemmel, Fausta Syana, Manele Ledra, Tharani Nagasara, Mervette Ledjeroud, Bahous Samia, Hafirassou Hadia, Benyoub Hazare, Ikrame El Jaghouni, Nessima Yelles, Sofia Zemouri, Mervette Ladjeroud, Salim Kerai, YunJeong In, Cristina Hobeanu, Celine Guidoux, Lucie Cabrejo, Bertrand Lapergue, Candice Sabben, Jaime Gonzalez-Valcarcel, Ricardo Rigual, Gaia Sirimarco, Anna Martin-Bechet, Elena Viedma, Ioan Avram, Yves Samson, Charlotte Rosso, Sophie Crozier, Sara Leder, Anne Léger, Sandrine Deltour, Gurkan Mutlu, Marion Yger, Chiara Zavanone, Flore Baronnet, Christine Pires, Adrien Wang, Serge Evrard, Maya Tchikviladze, Frédéric Bourdain, Delphine Lopez, Laetitia Bayon de la Tour, Marie-Laure Chadenat, Duc Long Duong, Solène Genty, Catherine Hirel, Chantal Nifle, Jérôme Servan, Daniela Stanciu, Veronica Sudacevschi, Mélissa Tir, Anne-Cécile Troussière, Jennifer Yeung, Anne-Céline Zeghoudi, Ikram Tidafi-Bayou, Sylvain Lachaud, Tae-Hee Cho, Laura Mechtouff, Thomas Ritzenthaller, Laurent Derex, Carlo Albanesi, Elodie Ong, Amandine Benoit, Nadia Berhoune, Sandra Felix, Maud Esteban-Mader, Igor Sibon, Annabelle Kazadi, François Rouanet, Pauline Renou, Sabrina Debruxelles, Mathilde Poli, Sharmila Sagnier, Jean-Louis Mas, Valérie Domigo, Catherine Lamy, Eric Bodiguel, Jérôme Grimaud, Valentin Bohotin, Michael Obadia, Erwan Morvan, Gilles Rodier, Wilfried Vadot, Hilde Hénon, Charlotte Cordonnier, Frédéric Dumont, Marie Bodenant, Christian Lucas, Solène Moulin, Nelly Dequatre, Sonia Alamowitch, Jean-Paul Muresan, Thomas Drouet, Magalie Gallea, Marie-Amélie Dalloz, Stephen Delorme, Philippe Loisel, Carine Bonnin, Virginie Bernigal, Guy Victor Osseby, Marie Hervieu-BègueMarsac, Pierre Garnier, Sandrine Accassat, Magali Epinat, Jérôme Varvat, Doïna Marinescu, Aude Triquenot-Bagan, Ozlem Ozkul- Wermester, Frédéric Philippeau, Anne Vieillart, Annie Lannuzel, Alice Demoly, Valérie Wolff, Mihaela Diaconu, Marc Bataillard, Francisco Macian Montoro, Frédéric Faugeras, Laeticia Gimenez, Françoise Abdallah-Lebeau, Serge Timsit, Irina Viakhireva-Dovganyuk, Anne Tirel-Badets, François-Mathias Merrien, Philippe Goas, François Rouhart, Aurore Jourdain, Benoit Guillon, Fanny Hérissson, Mathieu Sevin-Allouet, Nathalie Nasr, Jean-Marc Olivot, Alderic Lecluse, Guillaume Marc, null Hamon, Vincent de la Sayette, Marion Apoil, Li Lin, Julien Cogez, Sophie Guettier, Olivier Godefroy, Chantal Lamy, Jean-Marc Bugnicourt, Grégory Taurin, Marc Mérienne, Julien Gere, Anne-Marie Chessak, Tarik Habet, Anna Ferrier, Nathalie Bourgois, Dominique Minier, Marie Caillier-Minier, Fabienne Contégal- Callier, Philippe Vion, Yvan Vaschalde, Mohammed El Amrani, null Emilie, Mathieu Zuber, Marie Bruandet, Claire Join- Lambert, Pierre-Yves Garcia, Isabelle Serre, Jean-Marc Faucheux, Fatia Radji, Elena Leca-Radu, Thomas Debroucker, Rodica Cumurcuc, Serkan Cakmak, Stéphane Peysson, Emmanuel Ellie, Patricia Bernady, Thierry Moulin, Paola Montiel, Eugeniu Revenco, Pierre Decavel, Elisabeth Medeiros, Myriam Bouveret, Pierre Louchart, Claudia Vaduva, Grégory Couvreur, Eric Sartori, null Alnajar-Carpentier, Michèle Levasseur, Jean-Philippe Neau, Xavier Vandamme, Isabelle Meresse, null Stantescu, Canan Ozsancak, Katell Beauvais, Pascal Auzou, Joséphine Amevigbe, Francis Vuillemet, Marie-Hélène Dugay-Arentz, Gabriela Carelli, Mikel Martinez, Marcel Maillet-Vioud, Jean-Pierre Escaillas, Stéphane Chapuis, Jean Tardy, Eric Manchon, Olivier Varnet, Yong-Jae Kim, Yoonkyung Chang, Tae-Jin Song, Jong Sung Kim, Jung-Hoon Han, Kyung Chul Noh, Eun-Jae Lee, Dong-Wha Kang, Sun Uck Kwon, Boseoung Kwon, Seongho Park, Dongwhane Lee, Hyuk Sung Kwon, Daeun Jeong, MinHwan Lee, Joonggoo Kim, Hanbin Lee, Hyo Jung Nam, Sang Hun Lee, Bum Joon Kim, Jae-kwan Cha, DaeHyun Kim, Rae Young Kim, Sang Wuk Sohn, Dong-Hyun Shim, Hyungjin Lee, Hyun-Wook Nah, Sang Min Sung, Kyung Bok Lee, Jeong Yoon Lee, Jee Eun Yoon, Eung-Gyu Kim, Jung Hwa Seo, Yong-Won Kim, Yangha Hwang, Man Seok Park, Joon-Tae Kim, Kang-Ho Choi, Hyo Suk Nam, Ji Hoe Heo, Young Dae Kim, In Gun Hwang, Hyung Jong Park, Kyoung Sub Kim, Jang Hyun Baek, Dong Beom Song, Joon Sang Yoo, Jong-Moo Park, Ohyun Kwon, Woong-Woo Lee, Jung-Ju Lee, Kyusik Kang, Byung Kun Kim, Jae-Sung Lim, Mi Sun Oh, Kyung-Ho Yu, Bora Hong, Mihoon Jang, Seyoung Jang, Jung Eun Jin, Jei Kim, Hye Seon Jeong, Keun Sik Hong, Hong Kyun Park, Yong Jin Cho, Oh Young Bang, Keun Seo, Jongwon Chung, Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Asan Medical Center [Seoul, South Korea] (AMC), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Physiopathologie et épidémiologie cérébro-cardiovasculaire [Dijon] (PEC2), Université de Bourgogne (UB)-Université Bourgogne Franche-Comté [COMUE] (UBFC), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Equipe Avenir. University of Burgundy, Hallym University Sacred Heart Hospital [Anyang, South Korea] (HUS2H), Hôpital Pasteur [Nice] (CHU), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hospices Civils de Lyon (HCL), Hôpital Lariboisière-Fernand-Widal [APHP], Université Paris Diderot - Paris 7 (UPD7), Université Sorbonne Paris Cité (USPC), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), CHU Amiens-Picardie, Treat Stroke to Target Investigators*: Pierre-Jean Touboul, Didier Leys, Yannick Béjot, Fernando Pico, Emmanuel Touzé, Gregory Ducrocq, Jérémy Abtan, Olivier Varenne, Pierre-Jean Touboul, Agnes Kemmel, Fausta Syana, Manele Ledra, Tharani Nagasara, Mervette Ledjeroud, Bahous Samia, Hafirassou Hadia, Benyoub Hazare, Ikrame El Jaghouni, Nessima Yelles, Sofia Zemouri, Mervette Ladjeroud, Salim Kerai, YunJeong In, Cristina Hobeanu, Celine Guidoux, Lucie Cabrejo, Bertrand Lapergue, Candice Sabben, Jaime Gonzalez-Valcarcel, Ricardo Rigual, Gaia Sirimarco, Anna Martin-Bechet, Elena Viedma, Ioan Avram, Yves Samson, Charlotte Rosso, Sophie Crozier, Sara Leder, Anne Léger, Sandrine Deltour, Gurkan Mutlu, Marion Yger, Chiara Zavanone, Flore Baronnet, Christine Pires, Bertrand Lapergue, Adrien Wang, Serge Evrard, Maya Tchikviladze, Frédéric Bourdain, Delphine Lopez, Fernando Pico, Laetitia Bayon de la Tour, Marie-Laure Chadenat, Duc Long Duong, Solène Genty, Catherine Hirel, Gurkan Mutlu, Chantal Nifle, Jérôme Servan, Daniela Stanciu, Veronica Sudacevschi, Mélissa Tir, Anne-Cécile Troussière, Jennifer Yeung, Anne-Céline Zeghoudi, Ikram Tidafi-Bayou, Sylvain Lachaud, Tae-Hee Cho, Laura Mechtouff, Thomas Ritzenthaller, Laurent Derex, Carlo Albanesi, Elodie Ong, Amandine Benoit, Nadia Berhoune, Sandra Felix, Maud Esteban-Mader, Igor Sibon, Annabelle Kazadi, François Rouanet, Pauline Renou, Sabrina Debruxelles, Mathilde Poli, Sharmila Sagnier, Jean-Louis Mas, Valérie Domigo, Catherine Lamy, Eric Bodiguel, Jérôme Grimaud, Valentin Bohotin, Michael Obadia, Candice Sabben, Erwan Morvan, Gilles Rodier, Wilfried Vadot, Hilde Hénon, Charlotte Cordonnier, Frédéric Dumont, Marie Bodenant, Christian Lucas, Solène Moulin, Nelly Dequatre, Sonia Alamowitch, Jean-Paul Muresan, Thomas Drouet, Magalie Gallea, Marie-Amélie Dalloz, Stephen Delorme, Marion Yger, Yannick Béjot, Philippe Loisel, Carine Bonnin, Virginie Bernigal, Guy Victor Osseby, Marie Hervieu-BègueMarsac, Pierre Garnier, Sandrine Accassat, Magali Epinat, Jérôme Varvat, Doïna Marinescu, Aude Triquenot-Bagan, Ozlem Ozkul-Wermester, Frédéric Philippeau, Anne Vieillart, Annie Lannuzel, Alice Demoly, Valérie Wolff, Mihaela Diaconu, Marc Bataillard, Francisco Macian Montoro, Frédéric Faugeras, Laeticia Gimenez, Françoise Abdallah-Lebeau, Serge Timsit, Irina Viakhireva-Dovganyuk, Anne Tirel-Badets, François-Mathias Merrien, Philippe Goas, François Rouhart, Aurore Jourdain, Benoit Guillon, Fanny Hérissson, Mathieu Sevin-Allouet, Nathalie Nasr, Jean-Marc Olivot, Alderic Lecluse, Guillaume Marc, Hamon, Emmanuel Touzé, Vincent de la Sayette, Marion Apoil, Li Lin, Julien Cogez, Sophie Guettier, Olivier Godefroy, Chantal Lamy, Jean-Marc Bugnicourt, Grégory Taurin, Marc Mérienne, Julien Gere, Anne-Marie Chessak, Tarik Habet, Anna Ferrier, Nathalie Bourgois, Dominique Minier, Marie Caillier-Minier, Fabienne Contégal-Callier, Philippe Vion, Yvan Vaschalde, Mohammed El Amrani, Emilie, Mathieu Zuber, Marie Bruandet, Claire Join-Lambert, Pierre-Yves Garcia, Isabelle Serre, Jean-Marc Faucheux, Fatia Radji, Elena Leca-Radu, Thomas Debroucker, Rodica Cumurcuc, Serkan Cakmak, Stéphane Peysson, Emmanuel Ellie, Patricia Bernady, Thierry Moulin, Paola Montiel, Eugeniu Revenco, Pierre Decavel, Elisabeth Medeiros, Myriam Bouveret, Pierre Louchart, Claudia Vaduva, Grégory Couvreur, Eric Sartori, Alnajar-Carpentier, Michèle Levasseur, Pierre Louchart, Jean-Philippe Neau, Xavier Vandamme, Isabelle Meresse, Stantescu, Marc Bataillard, Canan Ozsancak, Katell Beauvais, Pascal Auzou, Joséphine Amevigbe, Francis Vuillemet, Marie-Hélène Dugay-Arentz, Gabriela Carelli, Mikel Martinez, Marcel Maillet-Vioud, Jean-Pierre Escaillas, Stéphane Chapuis, Jean Tardy, Eric Manchon, Olivier Varnet, Yong-Jae Kim, Yoonkyung Chang, Tae-Jin Song, Jong Sung Kim, Jung-Hoon Han, Kyung Chul Noh, Eun-Jae Lee, Dong-Wha Kang, Sun Uck Kwon, Boseoung Kwon, Seongho Park, Dongwhane Lee, Hyuk Sung Kwon, Daeun Jeong, MinHwan Lee, Joonggoo Kim, Hanbin Lee, Hyo Jung Nam, Sang Hun Lee, Bum Joon Kim, Jae-Kwan Cha, DaeHyun Kim, Rae Young Kim, Sang Wuk Sohn, Dong-Hyun Shim, Hyungjin Lee, Hyun-Wook Nah, Sang Min Sung, Kyung Bok Lee, Jeong Yoon Lee, Jee Eun Yoon, Eung-Gyu Kim, Jung Hwa Seo, Yong-Won Kim, Yangha Hwang, Man Seok Park, Joon-Tae Kim, Kang-Ho Choi, Hyo Suk Nam, Ji Hoe Heo, Young Dae Kim, In Gun Hwang, Hyung Jong Park, Kyoung Sub Kim, Jang Hyun Baek, Dong Beom Song, Joon Sang Yoo, Jong-Moo Park, Ohyun Kwon, Woong-Woo Lee, Jung-Ju Lee, Kyusik Kang, Byung Kun Kim, Jae-Sung Lim, Mi Sun Oh, Kyung-Ho Yu, Bora Hong, Mihoon Jang, Seyoung Jang, Jung Eun Jin, Jei Kim, Hye Seon Jeong, Keun Sik Hong, Hong Kyun Park, Yong Jin Cho, Oh Young Bang, Keun Seo, Jongwon Chung, and CarMeN, laboratoire
Subjects: Adult, Male, [SDV]Life Sciences [q-bio], Coronary Artery Disease, LDL, Young Adult, Predictive Value of Tests, Risk Factors, Secondary Prevention, Humans, cardiovascular diseases, Aged, Ischemic Stroke, Advanced and Specialized Nursing, Aged, 80 and over, Anticholesteremic Agents, Incidence, cholesterol, Anticoagulants, Cholesterol, LDL, Middle Aged, Ezetimibe, Intracranial Arteriosclerosis, [SDV] Life Sciences [q-bio], Ischemic Attack, Transient, Hypertension, Female, Neurology (clinical), atherosclerosis, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cardiology and Cardiovascular Medicine, Intracranial Hemorrhages
Abstract: Background and Purpose: Although statins are effective in secondary prevention of ischemic stroke, they are also associated with an increase risk of intracranial hemorrhage (ICH) in certain conditions. In the TST trial (Treat Stroke to Target), we prespecified an exploration of the predictors of incident ICH. Methods: Patients with ischemic stroke in the previous 3 months or transient ischemic attack within the previous 15 days and evidence of cerebrovascular or coronary artery atherosclerosis were randomly assigned in a 1:1 ratio to a target LDL (low-density lipoprotein) cholesterol of Results: Among 2860 patients enrolled, 31 incident ICH occurred over a median follow-up of 3 years (18 and 13 in the lower and higher target group, 3.21/1000 patient-years [95% CI, 2.38–4.04] and 2.32/1000 patient-years [95% CI, 1.61–3.03], respectively). While there were no baseline predictors of ICH, uncontrolled hypertension (HR, 2.51 [95% CI, 1.01–6.31], P =0.041) and being on anticoagulant (HR, 2.36 [95% CI, 1.00–5.62], P =0.047)] during the trial were significant predictors. On-treatment low LDL cholesterol was not a predictor of ICH. Conclusions: Targeting an LDL cholesterol of Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01252875; EUDRACT identifier: 2009-A01280-57.
Published: 2021

161. Impact of Expanded Hemodialysis Using Medium Cut-off Dialyzer on Quality of Life: Application of Dynamic Patient-Reported Outcome Measurement Tool

Author: Patricia Jarosz, Fabio R Salerno, Christopher W. McIntyre, Sandrine Lemoine, Jarrin D. Penny, CarMeN, laboratoire, University of Western Ontario (UWO), 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), Lawson Health Research Institute, and London Health Sciences Center (LHSC)
Subjects: medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), medicine.medical_treatment, [SDV]Life Sciences [q-bio], Prom, law.invention, Quality of life, Randomized controlled trial, law, Health care, Internal Medicine, medicine, Original Research, hemodialysis, business.industry, Expanded dialysis, [SDV] Life Sciences [q-bio], Nephrology, Sample size determination, patient reported outcome measures, Physical therapy, symptoms, Patient-reported outcome, health-related quality-of-life, Hemodialysis, business
Abstract: Rationale & Objective Current hemodialysis (HD) treatments have limited ability to clear larger-molecular-weight uremic toxins. Retention is associated with increased symptom burden, low health-related quality of life (HRQoL), and high mortality. Improved clearance, using novel medium cut-off dialyzers, termed expanded HD (HDx), may be associated with improved subjective experience. We have previously developed a dynamic patient-reported outcome measure (PROM) instrument to allow iterative recording to better appreciate the overall burden of disease and assess the impact of therapy changes. Study Design Single-center interventional pilot study. Setting & Participants 28 patients established on maintenance HD, London, Ontario, Canada. Intervention Initial study consisting of 2-week observation (baseline-conventional high-flux HD) followed by 12 weeks of HDx. HRQoL was assessed using the dynamic PROM instrument thrice weekly (enabled in a dedicated app as the London Evaluation of Illness [LEVIL]). Extension phase; 2-week baseline with 24 weeks of HDx and 8-week washout. Outcomes Principal aim was to establish whether HDx therapy was associated with improved HRQoL, evidence of dose-dependant response, and whether effects were durable over time, using LEVIL. Results Patients with lower LEVIL scores (, Graphical abstract
Published: 2021

162. Fatal Neonatal DOLK-CDG as a Rare Form of Syndromic Ichthyosis

Author: Katalin Komlosi, Olivier Claris, Sophie Collardeau-Frachon, Julia Kopp, Ingrid Hausser, Juliette Mazereeuw-Hautier, Nathalie Jonca, Andreas D. Zimmer, Damien Sanlaville, Judith Fischer, University of Freiburg [Freiburg], Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Heidelberg University Hospital [Heidelberg], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Fédératif de Biologie (IFB), Institut NeuroMyoGène (INMG), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and CarMeN, laboratoire
Subjects: DOLK, [SDV]Life Sciences [q-bio], syndromic ichthyosis, Mendelian disorders of cornification, QH426-470, whole exome sequencing, [SDV] Life Sciences [q-bio], interest, or financial relationships that could be construed as a potential conflict of, Genetics, Molecular Medicine, Genetics (clinical), Original Research, congenital disorders of glycosylation
Abstract: Neonatal collodion baby or ichthyosis can pose a diagnostic challenge, and in many cases, only additional organ involvement or the course of the disease will help differentiate between non-syndromic and syndromic forms. Skin abnormalities are described in about 20% of the congenital disorders of glycosylation (CDG). Among those, some rare CDG forms constitute a special group among the syndromic ichthyoses and can initially misdirect the diagnosis towards non-syndromic genodermatosis. DOLK-CDG is such a rare subtype, resulting from a defect in dolichol kinase, in which the congenital skin phenotype (often ichthyosis) is later associated with variable extracutaneous features such as dilatative cardiomyopathy, epilepsy, microcephaly, visual impairment, and hypoglycemia and may lead to a fatal course. We report two neonatal cases of lethal ichthyosis from the same family, with distal digital constrictions and a progressive course leading to multi-organ failure and death. Postmortem trio whole-exome sequencing revealed the compound heterozygous variants NM_014908.3: c.1342G>A, p.(Gly448Arg) and NM_014908.3: c.1558A>G, p.(Thr520Ala) in the DOLK gene in the first affected child, which were confirmed in the affected sibling. Reduced staining with anti-α-Dystroglycan antibody was observed in frozen heart tissue of the second child as an expression of reduced O-mannosylation due to the dolichol kinase deficiency. In addition to the detailed dermatopathological changes, both cases presented hepatic and extrahepatic hemosiderosis on histological examination. Our patients represent an early and fatal form of DOLK-CDG with a striking presentation at birth resembling severe collodion baby. Both cases emphasize the phenotypic variability of glycosylation disorders and the importance to broaden the differential diagnosis of ichthyosis and to actively search for organ involvement in neonates with ichthyosis.
Published: 2021

163. Comparison of α-Tocopherol, α-Tocopherol Acetate, and α-Tocopheryl Polyethylene Glycol Succinate 1000 Absorption by Caco-2 TC7 Intestinal Cells

Author: Claire Bordat, Emmanuelle Reboul, Charlotte Halimi, Marion Nowicki, Charlotte Cuerq, Emilie Blond, Noël Peretti, 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), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), and CarMeN, laboratoire
Subjects: 0301 basic medicine, Vitamin, Enterocyte, micelles, [SDV]Life Sciences [q-bio], medicine.medical_treatment, alpha-Tocopherol, Biological Availability, TPGS, Context (language use), enterocyte, lcsh:TX341-641, Polyethylene glycol, vitamin E, Tocofersolan, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, tocofersolan, medicine, Humans, Tocopherol, Intestinal Mucosa, intestine, 030109 nutrition & dietetics, Nutrition and Dietetics, Chromatography, Communication, Vitamin E, food and beverages, Bioavailability, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Intestinal Absorption, chemistry, Dietary Supplements, 030211 gastroenterology & hepatology, Caco-2 Cells, bioavailability, lcsh:Nutrition. Foods and food supply, Food Science
Abstract: International audience; (1) Background: vitamin E is often supplemented in the form of tocopherol acetate, but it has poor bioavailability and can fail to correct blood tocopherol concentrations in some patients with severe cholestasis. In this context, α-tocopheryl polyethylene glycol succinate 1000 (TPGS) has been of value, but very little is known about the mechanisms of its absorption. The aim of our work was to evaluate the mechanisms of absorption/secretion of TPGS compared to tocopherol acetate (TAC) and α-tocopherol by human enterocyte-like Caco-2 TC7 cells. (2) Methods: two weeks post-confluence Caco-2 cells were incubated with tocopherol- or TAC- or TPGS-rich mixed micelles up to 24 h and, following lipid extraction, TAC and tocopherol amounts were measured by high performance liquid chromatography (HPLC) in apical, cellular, and basolateral compartments. (3) Results: at equivalent concentrations of tocopherol in the apical side, the amounts of tocopherol secreted at the basolateral pole of Caco-2 cells are (i) significantly greater when the tocopherol is in the free form in the micelles; (ii) intermediate when it is in the TAC form in the micelles (p \textless 0.001); and (iii) significantly lower with the TPGS form (p \textless 0.0001). Interestingly, our results show, for the first time, that Caco-2 cells secrete one or more esterified forms of the vitamin contained in TPGS at the basolateral side.
Published: 2021

164. Serious adverse events and their impact on functional outcome in acute ischemic stroke in the WAKE-UP trial

Author: Eckhard Schlemm, Robin Lemmens, Norbert Nighoghossian, Bastian Cheng, Salvador Pedraza, Martin Ebinger, Vincent Thijs, Christian Gerloff, Claus Z Simonsen, Florent Boutitie, Märit Jensen, Götz Thomalla, Fanny Quandt, Keith W. Muir, Iris Lettow, Matthias Endres, Jochen B. Fiebach, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Hospices Civils de Lyon (HCL), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Austin Health, University of Melbourne, University Hospitals Leuven [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Campus Gasthuisberg, University of Glasgow, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta - Girona Biomedical Research Institute (IDIBGI), Aarhus University Hospital, and CarMeN, laboratoire
Subjects: Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, Magnetic resonance imaging, Double-Blind Method, Fibrinolytic Agents, Internal medicine, parasitic diseases, medicine, magnetic resonance imaging, pneumonia, Humans, 030212 general & internal medicine, Adverse effect, adverse drug event, Acute ischemic stroke, thrombolytic therapy, Aged, Ischemic Stroke, Advanced and Specialized Nursing, Ischemic stroke, medicine.diagnostic_test, Wake up stroke, business.industry, wake-up stroke, Recovery of Function, Pneumonia, Middle Aged, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Thrombolytic therapy, Adverse drug event, Tissue Plasminogen Activator, Cardiology, Female, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, Wake-up stroke, 030217 neurology & neurosurgery
Abstract: Background and Purpose: During the first days and weeks after an acute ischemic stroke, patients are prone to complications that can influence further treatment, recovery, and functional outcome. In clinical trials, severe complications are recorded as serious adverse events (SAE). We analyzed the effect of SAE on functional outcome and predictors of SAE in the randomized controlled WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke). Methods: We performed a post hoc analysis of WAKE-UP, a multicenter, randomized, placebo-controlled clinical trial of magnetic resonance imaging-guided intravenous thrombolysis with alteplase in patients with acute ischemic stroke and unknown time of onset. Functional outcome was assessed by the modified Rankin Scale 90 days after the stroke. SAE were reported to a central safety desk and recorded and categorized by organ system using Medical Dictionary for Regulatory Activities terminology. We used logistic regression analysis to determine the effect of SAE on functional outcome and linear multiple regression analysis to identify baseline predictors of SAE. Results: Among 503 patients randomized, 199 SAE were reported for n=110 (22%) patients. Of those patients who did suffer a SAE, 20 (10%) had a fatal outcome. Patients suffering from at least one SAE had a lower odds of reaching a favorable outcome (modified Rankin Scale score of 0–1) at 90 days (adjusted odds ratio, 0.36 [95% CI, 0.21–0.61], P P =0.04) and male sex ( P =0.01) were predictors for the occurrence of SAE. Conclusions: SAEs were observed in about one in 5 patients, were more frequent in elderly and male patients and were associated with worse functional outcome. These results may help to assess the risk of SAE in future stroke trials and create awareness for severe complications after stroke in clinical practice. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01525290. URL: https://eudract.ema.europa.eu ; Unique identifier: 2011-005906-32.
Published: 2021

165. Updating MISEV: Evolving the minimal requirements for studies of extracellular vesicles

Author: Kenneth W Witwer, Deborah CI Goberdhan, Lorraine O'Driscoll, Clotilde Théry, Joshua A Welsh, Cherie Blenkiron, Edit I Buzás, Dolores Di Vizio, Uta Erdbrügger, Juan M Falcón‐Pérez, Qing‐Ling Fu, Andrew F Hill, Metka Lenassi, Jan Lötvall, Rienk Nieuwland, Takahiro Ochiya, Sophie Rome, Susmita Sahoo, Lei Zheng, Johns Hopkins University School of Medicine [Baltimore], University of Oxford, Trinity College Dublin, Immunité et cancer (U932), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), University of Auckland [Auckland], Semmelweis University [Budapest], Cedars-Sinai Medical Center, University of Virginia, Ikerbasque - Basque Foundation for Science, Sun Yat-Sen University [Guangzhou] (SYSU), La Trobe University, University of Ljubljana, University of Gothenburg (GU), University of Amsterdam [Amsterdam] (UvA), Tokyo Medical University, 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), Icahn School of Medicine at Mount Sinai [New York] (MSSM), Southern Medical University [Guangzhou], CarMeN, laboratoire, Laboratory Specialized Diagnostics & Research, ACS - Microcirculation, CCA - Cancer biology and immunology, and CCA - Imaging and biomarkers
Subjects: standardization, Histology, QH573-671, [SDV]Life Sciences [q-bio], Cell Biology, exosomes, Reference Standards, rigor, [SDV] Life Sciences [q-bio], ectosomes, Editorial, MISEV, Humans, extracellular vesicles, Cytology, microvesicles, reproducibility
Abstract: International audience; The minimal information for studies of extracellular vesicles (EVs, MISEV) is a field-consensus rigour initiative of the International Society for Extracellular Vesicles (ISEV). The last update to MISEV, MISEV2018, was informed by input from more than 400 scientists and made recommendations in the six broad topics of EV nomenclature, sample collection and pre-processing, EV separation and concentration, characterization, functional studies, and reporting requirements/exceptions. To gather opinions on MISEV and ideas for new updates, the ISEV Board of Directors canvassed previous MISEV authors and society members. Here, we share conclusions that are relevant to the ongoing evolution of the MISEV initiative and other ISEV rigour and standardization efforts.
Published: 2021

166. Back off to better blow up: acute GFR decrease at SGLT-2 inhibitor initiation

Author: Team1 Carmen, Carmen Lab, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and CarMeN, laboratoire
Subjects: 0301 basic medicine, medicine.medical_specialty, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Urology, Renal function, Nephropathy, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, Post-hoc analysis, medicine, Humans, Protein restriction, Canagliflozin, Renal Insufficiency, Chronic, Sodium-Glucose Transporter 2 Inhibitors, urogenital system, business.industry, medicine.disease, 3. Good health, Blockade, [SDV] Life Sciences [q-bio], 030104 developmental biology, Diabetes Mellitus, Type 2, Nephrology, business, Glomerular Filtration Rate, Kidney disease, medicine.drug
Abstract: International audience; The drop in glomerular filtration rate often observed in the first weeks of nephroprotective treatment, whether because of protein restriction or renin-angiotensin system blockade, can be interpreted as a marker of the relationship between the intensity of baseline glomerular anomalies and the potential treatment benefit. In this issue, Oshima et al. reported a post hoc analysis of the Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation (CREDENCE) study, the results of which confirm that such a relationship is also observed under sodium-glucose cotransporter 2 inhibition in diabetic patients with chronic kidney disease.
Published: 2021

167. Lung Recruitability Evaluated by Recruitment-to-Inflation Ratio and Lung Ultrasound in COVID-19 Acute Respiratory Distress Syndrome

Author: Emeric Chatelain, Laurent Argaud, Neven Stevic, Auguste Dargent, Martin Cour, Claude Guérin, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and CarMeN, laboratoire
Subjects: Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV]Life Sciences [q-bio], Acute respiratory distress, Critical Care and Intensive Care Medicine, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Correspondence, medicine, Humans, Prospective Studies, Prospective cohort study, Lung, ComputingMilieux_MISCELLANEOUS, Aged, Ultrasonography, Respiratory Distress Syndrome, business.industry, SARS-CoV-2, Follow up studies, COVID-19, 030208 emergency & critical care medicine, Middle Aged, Lung ultrasound, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, 030228 respiratory system, Cardiology, Female, business, Follow-Up Studies
Abstract: International audience; No abstract available
Published: 2021

168. 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

169. Tricuspid regurgitation: Light at the end of the tunnel?

Author: David Messika-Zeitoun, Julien Dreyfus, Carmen Lab, Team3 Carmen, Centre cardiologique du Nord (CCN), Services de Pneumologie, Exploration Fonctionnelle Respiratoire et Cardiologie (Hôpital Louis Pradel), Hospices Civils de Lyon (HCL), University of Ottawa [Ottawa], and CarMeN, laboratoire
Subjects: Heart Valve Prosthesis Implantation, Cardiac Catheterization, [SDV]Life Sciences [q-bio], Insuffisance tricuspide, Percutané, General Medicine, TRI-SCORE, Tricuspid Valve Insufficiency, [SDV] Life Sciences [q-bio], Tricuspid regurgitation, Treatment Outcome, Transcatheter, Pronostic, Humans, Surgery, Tricuspid Valve, Chirurgie, Cardiology and Cardiovascular Medicine, Outcome
Abstract: International audience; No abstract available
Published: 2021

170. A prospective observational study for justification, safety, and efficacy of a third dose of mRNA vaccine in patients receiving maintenance hemodialysis

Author: Bechade Clémence, Tivollier Jean-Michel, Cyrille Mathieu, Daures Jean-Pierre, Cécile Couchoud, Anne Ovize, Gabriel Jean-Marc, Halimi Jean Michel, Nguyen Jean-Michel, Bauwens Marc, Wolak Aurore, Testevuide Pascale, Laetitia Koppe, Iacobelli Silvia, Laurence Pellegrina, Mercadal Lucile, Jais Jean-Philippe, Toure Fatouma, Loos-Ayav Carole, Sarraj Ayman, Longlune Nathalie, Sautenent Bénédicte, Laurent Juillard, Cerasuolo Damiano, Gervolino Shirley, Tendron-Franzin Anaïs, Bayat Sahar, Emilie Kalbacher, Glowacki François, Boucaut Maitre Denis, Merle Sylvie, Devictor Bénédicte, Denis Fouque, Ranlin Alex, Maxime Espi, Olivier Thaunat, Chantrel François, Brunet Philippe, Emmanuel Morelon, Salmi Louis Rachid, Virginie Mathias, Monnet Elisabeth, Galland Roula, Edet Stéphane, Kazes Isabelle, Berard Etienne, Lavainne Fréderic, Schauder Nicole, Tiple Aurélien, Courivaud Cécile, Hazzan Marc, Nacher Mathieu, Vacher Coponat Henri, Laurain Emmanuelle, Caroline C. Pelletier, Vergnenegre Alain, Reydit Mathilde, Christine Bouz, Vigneau Cécile, E. Chalencon, Thomas Barba, Xavier Charmetant, Bemrah Abdelkader, Gentile Stéphanie, Merle Véronique, Moranne Olivier, Emmanuelle Cart-Tanneur, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Hôpital Edouard Herriot [CHU - 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), Eurofins Biomnis, Université de Lyon, Agence de la biomédecine [Saint-Denis la Plaine], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Registre REIN, École des Hautes Études en Santé Publique [EHESP] (EHESP), REIN Registry: Chantrel François, Reydit Mathilde, Tiple Aurélien, Bechade Clémence, Bemrah Abdelkader, Vigneau Cécile, Sautenent Bénédicte, Kazes Isabelle, Courivaud Cécile, Gabriel Jean-Marc, Edet Stéphane, Mercadal Lucile, Moranne Olivier, Toure Fatouma, Laurain Emmanuelle, Ranlin Alex, Longlune Nathalie, Glowacki François, Tivollier Jean-Michel, Brunet Philippe, Lavainne Fréderic, Berard Etienne, Sarraj Ayman, Bauwens Marc, Testevuide Pascale, Vacher Coponat Henri, Galland Roula, Schauder Nicole, Salmi Louis-Rachid, Cerasuolo Damiano, Tendron-Franzin Anaïs, Bayat Sahar, Halimi Jean Michel, Wolak Aurore, Gentile Stéphanie, Devictor Bénédicte, Monnet Elisabeth, Boucaut Maitre Denis, Nacher Mathieu, Merle Véronique, Jais Jean-Philippe, Daures Jean-Pierre, Vergnenegre Alain, Loos-Ayav Carole, Merle Sylvie, Hazzan Marc, Gervolino Shirley, Nguyen Jean-Michel, Iacobelli Silvia, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and CarMeN, laboratoire
Subjects: medicine.medical_specialty, T cell, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Interferon gamma release assay, Antibodies, Viral, Gastroenterology, Renal Dialysis, Internal medicine, Epidemiology, Medicine, Humans, Clinical Investigation, BNT162 Vaccine, Vaccines, Synthetic, business.industry, SARS-CoV-2, Incidence (epidemiology), COVID-19, Vaccination, [SDV] Life Sciences [q-bio], Titer, medicine.anatomical_structure, mRNA vaccine, Nephrology, Hemodialysis, Cohort, BNT162b2, mRNA Vaccines, business
Abstract: The level of protection achieved by the standard two doses of COVID-19 mRNA vaccines in patients receiving maintenance hemodialysis (MHD) remains unclear. To study this we used the French Renal Epidemiology and Information Network (REIN) Registry to compare the incidence and severity of 1474 cases of COVID-19 diagnosed in patients receiving MHD after none, one or two doses of vaccine. Vaccination significantly reduce COVID-19 incidence and severity but 11% of patients infected after two doses still died. Lack of vaccinal protection in patients naïve for SARS-CoV-2 could be due to defective Tfh response [38% patients with negative spike-specific CD4+ T cell interferon gamma release assay] and failure to generate viral neutralizing titers of anti-spike receptor binding domain (RBD) IgGs (63% patients with titer at or under 997 BAU/ml, defining low/no responders) after two doses of vaccine. To improve protection, a third dose of vaccine was administered to 75 patients [57 low/no responders, 18 high responders after two doses] from the ROMANOV cohort that prospectively enrolled patients receiving MHD vaccinated with BNT162b2 (Pfizer). Tolerance to the third dose was excellent. High responders to two doses did not generate more anti-RBD IgGs after three doses but had more side effects. Importantly, 31 (54%) of low/no responders to two doses reached neutralizing titers of anti-RBD IgGs after three doses. A positive interferon gamma release assay and/or suboptimal titer of anti-RBD IgGs after two doses were the only predictive variables for response to three doses in multivariate analysis. Thus, the standard scheme of vaccination insufficiently protects patients receiving MHD. Anti-RBD IgG and specific CD4+ T cell response after two doses can guide personalized administration of the third dose, which improves the humoral response of SARS-CoV-2 naïve patients receiving MHD., Graphical abstract
Published: 2021

171. Tissue Sodium Storage in Patients With Heart Failure: A New Therapeutic Target?

Author: Christopher W. McIntyre, Alireza Akbari, Robert S. McKelvie, Sandrine Lemoine, Fabio R Salerno, 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 of Western Ontario (UWO), Lawson Health Research Institute, University of Tabriz [Tabriz], London Health Sciences Center (LHSC), and CarMeN, laboratoire
Subjects: Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Sodium, Urology, heart failure, Renal function, chemistry.chemical_element, Pilot Projects, body mass index, Systemic inflammation, Renal Dialysis, Interquartile range, medicine, Humans, Radiology, Nuclear Medicine and imaging, Renal Insufficiency, Chronic, sodium, Aged, Skin, glomerular filtration rate, business.industry, Stroke Volume, Middle Aged, medicine.disease, Magnetic Resonance Imaging, [SDV] Life Sciences [q-bio], Cross-Sectional Studies, chemistry, inflammation, Heart failure, Female, Hemodialysis, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Body mass index, Biomarkers, Kidney disease
Abstract: Background: Preclinical data suggest sodium deposited (without water) in tissues may lead to aberrant remodeling and systemic inflammation, independently of fluid overload in patients with heart failure (HF). Tissue salt storage can be measured noninvasively and quantitatively with 23 Na-magnetic resonance imaging. We aimed to investigate the possibility that patients with HF complicated by renal dysfunction are subject to higher tissue sodium concentration exposure than patients with chronic kidney disease alone. Methods: We conducted an exploratory study including 18 patients with HF, 34 hemodialysis patients (with no meaningful renal clearance of sodium), and 31 patients with chronic kidney disease, with glomerular filtration rate matched to the patients with HF. Every patient underwent 23 Na-magnetic resonance imaging of the calf, to quantify tissue sodium and allow comparison among the 3 patient groups. Results: There were no differences in age, sex, and body mass index between groups. Median (interquartile range) skin sodium content in HF (31 [23–37] mmol/L) was very high and indistinguishable from skin sodium content in hemodialysis patients (30 [22–35] mmol/L), P =0.6. Patients with HF exhibited significantly higher skin sodium content than matched estimated glomerular filtration rate chronic kidney disease patients (22 [19–26] mmol/L), P =0.005. Median muscle sodium content in patients with HF was significantly higher than in patients with chronic kidney disease, P =0.002. There was no relationship with estimated glomerular filtration rate in patients with HF. We report a significant correlation between skin sodium and urinary sodium ( P =0.04) but no correlation with muscle sodium. Patients who were assessed as being volume depleted (sodium excretion fraction 1% ( P =0.03). Conclusions: We have demonstrated that patients with HF characteristically have very high levels of skin sodium storage, comparable to well-characterized extreme levels seen in patients with end-stage kidney disease requiring hemodialysis. 23 Na-magnetic resonance imaging may allow precision medicine in the management of this challenging group of patients with HF. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03004547.
Published: 2021

172. Intensive care-related loss of quality of life and autonomy at 6 months post-discharge: Does COVID-19 really make things worse?

Author: Fabrice, Thiolliere, Claire, Falandry, Bernard, Allaouchiche, Victor, Geoffray, Laurent, Bitker, Jean, Reignier, Paul, Abraham, Stephanie, Malaquin, Baptiste, Balança, Hélène, Boyer, Philippe, Seguin, Céline, Guichon, Marie, Simon, Arnaud, Friggeri, Charles-Hervé, Vacheron, P, Danin, Service d'anesthésie-réanimation [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hospices Civils de Lyon (HCL), Université de Lyon, VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Hôpital de la Croix-Rousse [CHU - HCL], Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Edouard Herriot [CHU - HCL], CHU Amiens-Picardie, Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire [Rennes], Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM ), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Pôle de Santé Publique [Lyon], AZUREA Study Group: Laurent Argaud, Bernard Floccard, Thomas Rimmele, Albrice Levrat, Stanislas Ledechowski, Remi Bruyere, Carole Schwebel, Benedicte Zerr, Luc Jarrige, Quentin Blanc, Jerome Morel, Olivier Baldesi, Gaëtan Plantefeve, Philippe Seguin, Claire Dahyot-Fizelier, Michel Bonnivard, J Roustan, S Vimeux, Ali Mofredj, Sami Alaya, Adel Maamar, Julio Badie, Bertrand Souweine, Gerald Choukroun, Oriane Fontaine, Jean Michel Constantin, Marc Gainier, Benoit Misset, Jean Claude Orban, Jean Reignier, Jean-Marc Doise, Olivier Millet, Laurent Favier, Berangere Jany, Ramin Ravan, Delphine Roux, Pierre Marie Bertrand, Nicolas Bele, Stéphanie Malaquin, Pierre Grégoire Guinot, Jean Pierre Quenot, Fanny Bounes, Claude Koubi, P Danin., CarMeN, laboratoire, 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), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Quality of life, Critical Care, [SDV]Life Sciences [q-bio], Aftercare, COVID-19, Critical Care and Intensive Care Medicine, Patient Discharge, [SDV] Life Sciences [q-bio], Intensive Care Units, Outcome Assessment, Health Care, Quality of Life, Humans, Prospective Studies, Autonomy, Aged
Abstract: Objective To compare old patients hospitalized in ICU for respiratory distress due to COVID-19 with old patients hospitalized in ICU for a non-COVID-19-related reason in terms of autonomy and quality of life. Design Comparison of two prospective multi-centric studies. Setting This study was based on two prospective multi-centric studies, the Senior-COVID-Rea cohort (COVID-19-diagnosed ICU-admitted patients aged over 60) and the FRAGIREA cohort (ICU-admitted patients aged over 70). Patients We included herein the patients from both cohorts who had been evaluated at day 180 after admission (ADL score and quality of life). Interventions None. Measurements and main results A total of 93 COVID-19 patients and 185 control-ICU patients were included. Both groups were not balanced on age, body mass index, mechanical ventilation, length of ICU stay, and ADL and SAPS II scores. We modeled with ordered logistic regression the influence of COVID-19 on the quality of life and the ADL score. After adjustment on these factors, we observed COVID-19 patients were less likely to have a loss of usual activities (aOR [95% CI] 0.47 [0.23; 0.94]), a loss of mobility (aOR [95% CI] 0.30 [0.14; 0.63]), and a loss of ADL score (aOR [95% CI] 0.30 [0.14; 0.63]). On day 180, 52 (56%) COVID-19 patients presented signs of dyspnea, 37 (40%) still used analgesics, 17 (18%) used anxiolytics, and 14 (13%) used antidepressant. Conclusions COVID-19-related ICU stay was not associated with a lower quality of life or lower autonomy compared to non-COVID-19-related ICU stay.
Published: 2021

173. Curcumin supplementation improves oxidative stress and inflammation biomarkers in patients undergoing hemodialysis: a secondary analysis of a randomized controlled trial

Author: Livia Alvarenga, Ludmila F. M. F. Cardozo, Beatriz O. Da Cruz, Bruna R. Paiva, Denis Fouque, Denise Mafra, Fluminense Federal University [Niterói], 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), Universidade Federal do Rio de Janeiro (UFRJ), and CarMeN, laboratoire
Subjects: Inflammation, Curcumin, Tumor Necrosis Factor-alpha, Urology, [SDV]Life Sciences [q-bio], [SDV] Life Sciences [q-bio], Oxidative Stress, Double-Blind Method, Nephrology, Renal Dialysis, Chronic kidney disease, Hemodialysis, Dietary Supplements, Humans, Renal Insufficiency, Chronic, Biomarkers
Abstract: International audience; BACKGROUND AND OBJECTIVES: Recent studies have shed light on the potential role of curcumin in mitigating inflammation in patients with chronic kidney disease (CKD). This study aimed to evaluate the effects of curcumin supplementation on plasma levels of markers of inflammation and oxidative stress in patients with CKD undergoing hemodialysis (HD). METHODS: These are secondary exploratory analyses from a previous double-blind, randomized controlled pilot study registered under ClinicalTrials.gov Identifier no. NCT00123456. It included 28 hemodialysis patients from a previous study divided into two groups: curcumin group (receiving juice with 2.5 g of turmeric 3×/week for 12 weeks) and a control group. The TNF-α, IL-6 and Ox-LDL plasma levels were measured by sandwich enzyme immunoassays ELISA; lipid peroxidation was measured by the reaction between malondialdehyde (MDA) and thiobarbituric acid. RESULTS: After 12 weeks of supplementation with curcumin, the TNF-α plasma levels were significantly reduced [from 15.0 (8.23-73.3) to 6.17 (1.11-55.0) pg/mL, p = 0.01]. CONCLUSION: 12 weeks of treatment with curcumin in HD patients resulted in a reduction in the biomarker of inflammation (TNF-α), confirming our previous hypothesis that curcumin has an anti-inflammatory effect.
Published: 2021

174. 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

175. Blood-derived miRNA levels are not correlated with metabolic or anthropometric parameters in obese pre-diabetic subjects but with systemic inflammation

Author: Prabu Paramasivam, Emmanuelle Meugnier, Kuppan Gokulakrishnan, Harish Ranjini, Lisa R. Staimez, Mary Beth Weber, K. M. Venkat Narayan, Hubert Vidal, Nikhil Tandon, Dorairaj Prabhakaran, Anjana Ranjit Mohan, Viswanathan Mohan, Sophie Rome, Muthuswamy Balasubramanyam, Indian Statistical Institute [Chennai], The University of New Mexico [Albuquerque], 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), National Institute of Mental Health and Neurosciences [Bangalore, Inde] (NIMHANS ), Emory University [Atlanta, GA], All India Institute of Medical Sciences [New Delhi], Department of Computer Science and Engineering [New Delhi], Indian Institute of Technology Delhi (IIT Delhi), Public Health Foundation of India [New Delhi] (PHFI), and CarMeN, laboratoire
Subjects: Blood Glucose, Male, Physiology, Nutritional Sciences, [SDV]Life Sciences [q-bio], Biochemistry, Endocrinology, Medical Conditions, Glucose Metabolism, Medicine and Health Sciences, Insulin, Public and Occupational Health, Immune Response, Multidisciplinary, Anthropometry, Fasting, Middle Aged, Body Fluids, Nucleic acids, [SDV] Life Sciences [q-bio], Blood, Physiological Parameters, Carbohydrate Metabolism, Medicine, Cytokines, Female, Anatomy, Waist Circumference, Research Article, Adult, Endocrine Disorders, Systole, Science, Immunology, Prediabetic State, Signs and Symptoms, Asian People, Genetics, Diabetes Mellitus, Humans, Obesity, Non-coding RNA, Exercise, Life Style, Nutrition, Inflammation, Natural antisense transcripts, Biology and life sciences, Body Weight, Physical Activity, Gene regulation, Diet, MicroRNAs, Metabolism, Metabolic Disorders, RNA, Gene expression, Clinical Medicine, Insulin Resistance
Abstract: As blood-derived miRNAs (c-miRNAs) are modulated by exercise and nutrition, we postulated that they might be used to monitor the effects of a lifestyle intervention (LI) to prevent diabetes development. To challenge this hypothesis, obese Asian Indian pre-diabetic patients were submitted to diet modifications and physical activity for 4 months (LI group) and compared to a control group which was given recommendations only. We have considered 2 periods of time to analyze the data, i.e.; a first one to study the response to the intervention (4 months), and a second one post-intervention (8 months). At basal, 4 months and 8 months post-intervention the levels of 17 c-miRNAs were quantified, selected either for their relevance to the pathology or because they are known to be modulated by physical activity or diet. Their variations were correlated with variations of 25 metabolic and anthropometric parameters and cytokines. As expected, fasting-glycaemia, insulin-sensitivity, levels of exercise- and obesity-induced cytokines were ameliorated after 4 months. In addition, the levels of 4 miRNAs (i.e.; miR-128-3p, miR-374a-5p, miR-221-3p, and miR-133a-3p) were changed only in the LI group and were correlated with metabolic improvement (insulin sensitivity, cytokine levels, waist circumference and systolic blood pressure). However, 8 months post-intervention almost all ameliorated metabolic parameters declined indicating that the volunteers did not continue the protocol on their own. Surprisingly, the LI positive effects on c-miRNA levels were still detected, and were even more pronounced 8 months post-intervention. In parallel, MCP-1, involved in tissue infiltration by immune cells, and Il-6, adiponectin and irisin, which have anti-inflammatory effects, continued to be significantly and positively modified, 8 months post-intervention. These data demonstrated for the first time, that c-miRNA correlations with metabolic parameters and insulin sensitivity are in fact only indirect and likely associated with the level systemic inflammation. More generally speaking, this important result explains the high variability between the previous studies designed to identify specific c-miRNAs associated with the severity of insulin-resistance. The results of all these studies should take into account the level of inflammation of the patients. In addition, this finding could also explain why, whatever the pathology considered (i.e.; cancers, diabetes, neurodegenerative disorders, inflammatory diseases) the same subset of miRNAs is always found altered in the blood of patients vs healthy subjects, as these pathologies are all associated with the development of inflammation.
Published: 2021

176. Effects of methylene blue on microcirculatory alterations following cardiac surgery: A prospective cohort study

Author: Matthias Jacquet-Lagrèze, Carole Maurin, Philippe Portran, Stéphane Junot, Rémi Schweizer, Bernard Allaouchiche, Jean-Luc Fellahi, Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Agressions Pulmonaires et Circulatoires dans le Sepsis - UR (APCSé), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and CarMeN, laboratoire
Subjects: Adult, medicine.medical_specialty, Mean arterial pressure, [SDV]Life Sciences [q-bio], Cardiac index, Hemodynamics, Vascular occlusion, law.invention, Cohort Studies, law, Internal medicine, medicine, Cardiopulmonary bypass, Humans, Prospective Studies, Vasoplegic syndrome, Cardiac Surgical Procedures, medicine.diagnostic_test, business.industry, Microcirculation, medicine.disease, Capillary refill, Cardiac surgery, [SDV] Life Sciences [q-bio], Methylene Blue, Anesthesiology and Pain Medicine, Cardiology, medicine.symptom, business
Abstract: International audience; BACKGROUND: Methylene blue is used as rescue therapy to treat catecholamine-refractory vasoplegic syndrome after cardiac surgery. However, its microcirculatory effects remain poorly documented. OBJECTIVE: We aimed to study microcirculatory abnormalities in refractory vasoplegic syndrome following cardiac surgery with cardiopulmonary bypass and assess the effects of methylene blue. DESIGN: A prospective open-label cohort study. SETTING: 20-Bed ICU of a tertiary care hospital. PATIENTS: 25 Adult patients receiving 1.5 mg kg-1 of methylene blue intravenously for refractory vasoplegic syndrome (defined as norepinephrine requirement more than 0.5 μg kg-1 min-1) to maintain mean arterial pressure (MAP) more than 65 mmHg and cardiac index (CI) more than 2.0 l min-1 m-2. MAIN OUTCOME MEASURES: Complete haemodynamic set of measurements at baseline and 1 h after the administration of methylene blue. Sublingual microcirculation was investigated by sidestream dark field imaging to obtain microvascular flow index (MFI), total vessel density, perfused vessel density and heterogeneity index. Microvascular reactivity was assessed by peripheral near-infrared (IR) spectroscopy combined with a vascular occlusion test. We also performed a standardised measurement of capillary refill time. RESULTS: Despite normalised CI (2.6 [2.0 to 3.8] l min-1 m-2) and MAP (66 [55 to 76] mmHg), patients with refractory vasoplegic syndrome showed severe microcirculatory alterations (MFI \textless 2.6). After methylene blue infusion, MFI significantly increased from 2.0 [0.1 to 2.5] to 2.2 [0.2 to 2.8] (P = 0.008), as did total vessel density from 13.5 [8.3 to 18.5] to 14.9 [10.1 to 14.7] mm mm-2 (P = 0.02) and perfused vessel density density from 7.4 [0.1 to 11.5] to 9.1 [0 to 20.1] mm mm-2 (P = 0.02), but with wide individual variation. Microvascular reactivity assessed by tissue oxygen resaturation speed also increased from 0.5 [0.1 to 1.8] to 0.7 [0.1 to 2.7]% s-1 (P = 0.002). Capillary refill time remained unchanged throughout the study. CONCLUSION: In refractory vasoplegic syndrome following cardiac surgery, we found microcirculatory alterations despite normalised CI and MAP. The administration of methylene blue could improve microvascular perfusion and reactivity, and partially restore the loss of haemodynamic coherence. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04250389.
Published: 2021

177. Ornithine Transcarbamylase – From Structure to Metabolism: An Update

Author: Christophe Moinard, Christelle Corne, John Rendu, Uwe Schlattner, Morgane Couchet, Béatrice Morio, C. Breuillard, Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire [Grenoble] (CHU), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), and CarMeN, laboratoire
Subjects: Physiology, [SDV]Life Sciences [q-bio], Ornithine transcarbamylase, Review, Biology, liver, chemistry.chemical_compound, Amino acid homeostasis, Physiology (medical), Citrulline, QP1-981, Inner mitochondrial membrane, intestine, chemistry.chemical_classification, diabetes, OTC deficiency, NASH, Metabolism, [SDV] Life Sciences [q-bio], Enzyme, interest, chemistry, Biochemistry, or financial relationships that could be construed as a potential conflict of, Mitochondrial matrix, Urea cycle, citrulline
Abstract: International audience; Ornithine transcarbamylase (OTC; EC 2.1.3.3) is a ubiquitous enzyme found in almost all organisms, including vertebrates, microorganisms, and plants. Anabolic, mostly trimeric OTCs catalyze the production of L-citrulline from L-ornithine which is a part of the urea cycle. In eukaryotes, such OTC localizes to the mitochondrial matrix, partially bound to the mitochondrial inner membrane and part of channeling multi-enzyme assemblies. In mammals, mainly two organs express OTC: the liver, where it is an integral part of the urea cycle, and the intestine, where it synthesizes citrulline for export and plays a major role in amino acid homeostasis, particularly of L-glutamine and L-arginine. Here, we give an overview on OTC genes and proteins, their tissue distribution, regulation, and physiological function, emphasizing the importance of OTC and urea cycle enzymes for metabolic regulation in human health and disease. Finally, we summarize the current knowledge of OTC deficiency, a rare X-linked human genetic disorder, and its emerging role in various chronic pathologies.
Published: 2021

178. 3-methylhistidine and clinical outcomes in maintenance haemodialysis patients

Author: Emilie Bres, Cécile Pagan, Anaïs Bouchara, Myriam Pastural, Samuel Granjon, Maurice Laville, Denis Fouque, Christophe O Soulage, Laetitia Koppe, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Laboratoire de Biologie Médicale MultiSites [Bron] (LBMMS), Hospices Civils de Lyon (HCL)-Centre de Biologie et Pathologie Est [Bron] (CBPE), Association pour l'Utilisation du Rein Artificiel Région Lyonnaise [Lyon] (AURAL), Cerballiance, and CarMeN, laboratoire
Subjects: Transplantation, [SDV]Life Sciences [q-bio], Methylhistidines, mortality, Actins, [SDV] Life Sciences [q-bio], cardiovascular events, 3-methylhistidine, maintenance hemodialysis, Nephrology, Renal Dialysis, Creatinine, lean tissue mass, Humans, Kidney Failure, Chronic, Biomarkers, Serum Albumin
Abstract: Background Chronic kidney disease is an important contributor to morbidity and mortality. 3-methylhistidine (3-MH) is the by-product of actin and myosin degradation reflecting skeletal muscle turnover. Markedly elevated 3-MH levels have been documented in uraemic patients, but the interpretation of high 3-MH concentration in maintenance haemodialysis (MHD) patients remains unclear. Indeed, it is not known whether elevated serum 3-MH levels are a marker of excessive muscle catabolism or a better lean tissue mass. Here, we evaluated the association between serum 3-MH levels and clinical outcomes in these patients. Methods Serum 3-MH concentration was measured by reverse-phase liquid chromatography/tandem mass spectrometry in a cohort of MHD patients. We analysed the relationships between various clinical/laboratory indices, lean tissue mass measured by bioimpedance spectroscopy, mortality and cardiovascular (CV) events. Results Serum 3-MH concentration was positively correlated with serum albumin, normalized protein catabolic rate (nPCR), simplified creatinine index (SCI) and lean tissue mass. Of 291 MHD patients, during a mean follow-up of 847 days, 91 patients died and 101 patients experienced a CV event. Survival was significantly better in patients with high 3-MH concentrations (P = .002). A higher level of 3-MH was also associated with a lower CV mortality and lower incidence of CV events (P = .015 and P Conclusion Elevated serum 3-MH concentration appears to be a marker of better lean tissue mass and nutritional status. Low serum 3-MH is a robust and independent predictor of CV events in the MHD population.
Published: 2021

179. Insulin pump initiation in outpatient settings: When technology facilitates new healthcare organizations

Author: Carmen Lab, Team2 Carmen, CarMeN, laboratoire, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Hospices Civils de Lyon (HCL)
Subjects: Insulin pump, Blood Glucose, medicine.medical_specialty, Technology, business.industry, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Insulins, General Medicine, [SDV] Life Sciences [q-bio], Endocrinology, Diabetes Mellitus, Type 1, Insulin Infusion Systems, Editorial, Health care, Outpatients, Internal Medicine, medicine, Humans, Hypoglycemic Agents, Insulin, Intensive care medicine, business, Delivery of Health Care, ComputingMilieux_MISCELLANEOUS
Abstract: International audience; No abstract available
Published: 2021

180. Serum Soluble Tumor Necrosis Factor Receptors 1 and 2 Are Early Prognosis Markers After ST-Segment Elevation Myocardial Infarction

Author: Paccalet, Alexandre, Crola Da Silva, Claire, Mechtouff, Laura, Amaz, Camille, Varillon, Yvonne, de Bourguignon, Charles, Cartier, Regine, Prieur, Cyril, Tomasevic, Danka, Genot, Nathalie, Leboube, Simon, Derimay, François, Rioufol, Gilles, Bonnefoy-Cudraz, Eric, Mewton, Nathan, Ovize, Michel, Bidaux, Gabriel, Bochaton, Thomas, CarMeN, laboratoire, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), Hôpital Louis Pradel [CHU - HCL], Centre d'Investigation Clinique [Bron] (CIC1407), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupement Hospitalier Est [Bron], Groupement Hospitalier Lyon-Est (GHE), and Université de Lyon
Subjects: [SDV] Life Sciences [q-bio], Pharmacology, myocardial infarction, soluble TNF receptor, interest, or financial relationships that could be construed as a potential conflict of, [SDV]Life Sciences [q-bio], Tnf, biomarker, Pharmacology (medical), cardiovascular diseases, prognosis, Original Research
Abstract: International audience; Background: As inflammation following ST-segment elevation myocardial infarction (STEMI) is both beneficial and deleterious, there is a need to find new biomarkers of STEMI severity. Objective: We hypothesized that the circulating concentration of the soluble tumor necrosis factor α receptors 1 and 2 (sTNFR1 and sTNFR2) might predict clinical outcomes in STEMI patients. Methods: We enrolled into a prospective cohort 251 consecutive STEMI patients referred to our hospital for percutaneous coronary intervention revascularization. Blood samples were collected at five time points: admission and 4, 24, 48 h, and 1 month after admission to assess sTNFR1 and sTNFR2 serum concentrations. Patients underwent cardiac magnetic resonance imaging at 1 month. Results: sTNFR1 concentration increased at 24 h with a median of 580.5 pg/ml [95% confidence interval (CI): 534.4-645.6]. sTNFR2 increased at 48 h with a median of 2,244.0 pg/ml [95% CI: 2090.0-2,399.0]. Both sTNFR1 and sTNFR2 peak levels were correlated with infarct size and left ventricular end-diastolic volume and inversely correlated with left ventricular ejection fraction. Patients with sTNFR1 or sTNFR2 concentration above the median value were more likely to experience an adverse clinical event within 24 months after STEMI [hazards ratio (HR): 8.8, 95% CI: 4.2-18.6, p \textless 0.0001 for sTNFR1; HR: 6.1, 95% CI: 2.5 -10.5, p = 0.0003 for sTNFR2]. Soluble TNFR1 was an independent predictor of major adverse cardiovascular events and was more powerful than troponin I (p = 0.04 as compared to the troponin AUC). Conclusion: The circulating sTNFR1 and sTNFR2 are inflammatory markers of morphological and functional injury after STEMI. sTNFR1 appears as an early independent predictor of clinical outcomes in STEMI patients.
Published: 2021
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181. It's never too early to beat your low-density lipoprotein cholesterol

Author: Gilles Barone-Rochette, François Mach, Denis Angoulvant, Cyrille Bergerot, Nathan Mewton, Gilles Lemesle, 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), Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), Institut Coeur Poumon [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires (RNMCD - U1011), 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), Alliance française pour les essais cliniques cardio-vasculaires - French Alliance for Cardiovascular Trials (FACT), Radiopharmaceutiques biocliniques (LRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Département de cardiologie [CHU de Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Geneva University Hospital (HUG), Service de néphrologie et immunologie clinique [CHRU Tours] (EA4245 UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours, Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 (RNMCD), and CarMeN, laboratoire
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], Prévention sécondaire, Low density lipoprotein cholesterol, 030204 cardiovascular system & hematology, Risk Assessment, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Traitements hypolipémiants, Internal medicine, medicine, Humans, Healthy Lifestyle, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Dyslipidemias, Ldl cholesterol, Secondary prevention, business.industry, Anticholesteremic Agents, Cholesterol, LDL, General Medicine, Lipid-lowering therapies, medicine.disease, [SDV] Life Sciences [q-bio], Maladie coronaire, Treatment Outcome, Cardiovascular Diseases, Heart Disease Risk Factors, LDL cholesterol, Cardiology, Cardiology and Cardiovascular Medicine, business, Risk Reduction Behavior, Beat (music), Biomarkers, LDL cholestérol
Abstract: International audience
Published: 2021

182. Characteristics and Outcome of COAPT-Eligible Patients in the MITRA-FR Trial

Author: Jean-François Obadia, Delphine Maucort-Boulch, Alec Vahanian, Jean-Noël Trochu, Bernard Iung, Florent Boutitie, Xavier Armoiry, David Messika-Zeitoun, Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, University of Ottawa [Ottawa], Hospices Civils de Lyon (HCL), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon, Université de Nantes (UN), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Matériaux, ingénierie et science [Villeurbanne] (MATEIS), 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)-Centre National de la Recherche Scientifique (CNRS), Hôpital Louis Pradel [CHU - HCL], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, and CarMeN, laboratoire
Subjects: Male, Cardiac Catheterization, medicine.medical_specialty, Time Factors, [SDV]Life Sciences [q-bio], Clinical Decision-Making, MEDLINE, heart failure, Eligibility Determination, 030204 cardiovascular system & hematology, Prosthesis Design, heart valve diseases, Risk Assessment, Severity of Illness Index, Outcome (game theory), 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Physiology (medical), Internal medicine, medicine, Humans, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Aged, Heart Valve Prosthesis Implantation, Clinical Trials as Topic, business.industry, Patient Selection, Mitral Valve Insufficiency, Recovery of Function, Middle Aged, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Treatment Outcome, Heart Valve Prosthesis, Heart failure, Disease Progression, Mitral Valve, Female, Cardiology and Cardiovascular Medicine, business
Abstract: International audience; No abstract available
Published: 2020

183. Ketone Bodies as Metabolites and Signalling Molecules at the Crossroad between Inflammation and Epigenetic Control of Cardiometabolic Disorders

Author: Nadia Bendridi, Anna Selmi, Aneta Balcerczyk, Luciano Pirola, 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 of Lódź, and CarMeN, laboratoire
Subjects: Epigenomics, Inflammation, Ketone Bodies/metabolism, Ketogenic, 3-Hydroxybutyric Acid, [SDV.BA] Life Sciences [q-bio]/Animal biology, 3-Hydroxybutyric Acid/pharmacology, [SDV.BA]Life Sciences [q-bio]/Animal biology, Organic Chemistry, General Medicine, Diet, Catalysis, cardiovascular diseases, Computer Science Applications, Inorganic Chemistry, histone PTMs, ketone bodies, Humans, Physical and Theoretical Chemistry, Diet, Ketogenic, Molecular Biology, Spectroscopy, histone β-hydroxybutyrylation
Abstract: For many years, it has been clear that a Western diet rich in saturated fats and sugars promotes an inflammatory environment predisposing a person to chronic cardiometabolic diseases. In parallel, the emergence of ketogenic diets, deprived of carbohydrates and promoting the synthesis of ketone bodies imitating the metabolic effects of fasting, has been shown to provide a possible nutritional solution to alleviating diseases triggered by an inflammatory environment. The main ketone body, β-hydroxybutyrate (BHB), acts as an alternative fuel, and also as a substrate for a novel histone post-translational modification, β-hydroxybutyrylation. β-hydroxybutyrylation influences the state of chromatin architecture and promotes the transcription of multiple genes. BHB has also been shown to modulate inflammation in chronic diseases. In this review, we discuss, in the pathological context of cardiovascular risks, the current understanding of how ketone bodies, or a ketogenic diet, are able to modulate, trigger, or inhibit inflammation and how the epigenome and chromatin remodeling may be a key contributor.
Published: 2022

184. Development and Survival of Human Ovarian Cells in Chitosan Hydrogel Micro-Bioreactor

Author: Elsa Labrune, Cyrielle Fournier, Benjamin Riche, Laurent David, Alexandra Montembault, Sophie Collardeau-Frachon, Mehdi Benchaib, Jacqueline Lornage, Jean Iwaz, Bruno Salle, CarMeN, laboratoire, Institut cellule souche et cerveau / Stem Cell and Brain Research Institute (U1208 Inserm - UCBL1 / SBRI - USC 1361 INRAE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre d’étude et de conservation des œufs et des spermatozoïdes humains [HCL, Lyon] (CECOS), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Université de Lyon, Hospices Civils de Lyon (HCL), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Service de Biostatistique-Bioinformatique [Lyon], Pôle de Santé Publique [Lyon], Ingénierie des Matériaux Polymères (IMP), 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 de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Département d'anatomopathologie, biopathologie, Centre Léon Bérard [Lyon], and Institut cellule souche et cerveau / Stem Cell and Brain Research Institute (SBRI)
Subjects: Ovary, chitosan, hydrogel, folliculogenesis, bioreactor, tissue culture technique, Hydrogels, Tissue Culture Techniques/methods, Chitosan, General Medicine, Tissue Culture Techniques, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Bioreactors, Humans, Female, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: Background and Objectives: To test the long-term ability of human ovarian cortex cells to develop in unconventional culture conditions. Materials and Methods. Ovarian cortex cells from fetuses aged 23 to 39 weeks gestation were cultured for 90 days in hollow chitosan hydrogel micro-bioreactors and concurrently in traditional wells. Various cell-type counts were considered. Results: With intact follicles as a denominator, the percentage of growing intact follicles at Day 0 varied widely between ovaries (0 to 31.7%). This percentage tended to increase or stay relatively constant in bioreactor as in control cultures; it tended more toward an increase over time in bioreactor vs. control cultures. Modeled percentages showed differences (though not significant) in favor of bioreactor cultures (16.12% difference at D50 but only 0.12% difference at D90). With all follicles present as a denominator, the percentage of growing primary and secondary follicles at D0 varied widely between ovaries (0 to 29.3%). This percentage tended to increase over time in bioreactor cultures but to decrease in control cultures. Modeled percentages showed significant differences in favor of bioreactor cultures (8.9% difference at D50 and 11.1% difference at D90). At D50 and D90, there were only few and sparse apoptotic cells in bioreactor cultures vs. no apoptotic cells in control cultures. Conclusions: Over three months, bioreactor folliculogenesis outperformed slightly traditional culture. This is an interesting perspective for follicle preservation and long-term toxicological studies.
Published: 2022

185. Peer-reviewing and medical publication

Author: Carmen Lab, Denis Fouque, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), and CarMeN, laboratoire
Subjects: [SDV] Life Sciences [q-bio], peer-review, reviewer, Transplantation, kindness, Nephrology, editor, [SDV]Life Sciences [q-bio], medical publication
Abstract: International audience; No abstract available
Published: 2022

186. 'Don’t Be Frail to Optimize Heart Failure Therapies!'

Author: Carmen Lab, Team3 Carmen, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), and CarMeN, laboratoire
Subjects: [SDV] Life Sciences [q-bio], Heart Failure, [SDV]Life Sciences [q-bio], Frail Elderly, Humans, frailty, Cardiology and Cardiovascular Medicine, heart failure with reduced ejection fraction, guideline-directed medical therapy, Aged
Abstract: International audience; No abstract available
Published: 2022

187. Comparison of clinical prediction rules for ruling out cirrhosis in nonalcoholic fatty liver disease (NAFLD)

Author: Danielle, Brandman, Marie, Boyle, Stuart, McPherson, Mark L, Van Natta, Arun J, Sanyal, Kris, Kowdley, Brent, Neuschwander-Tetri, Naga, Chalasani, Manal F, Abdelmalek, Norah A, Terrault, Art, McCullough, Ricki, Bettencourt, Cyrielle, Caussy, David E, Kleiner, Cynthia, Behling, James, Tonascia, Quentin M, Anstee, Rohit, Loomba, University of California [San Francisco] (UC San Francisco), University of California (UC), Newcastle University [Newcastle], Newcastle Upon Tyne Hospitals NHS Foundation Trust, Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Virginia Commonwealth University (VCU), Swedish Medical Center [Seattle, WA, USA] (SMC), Saint Louis University (SLU), Indiana University - Purdue University Indianapolis (IUPUI), Indiana University System, Duke University [Durham], University of Southern California (USC), Cleveland Clinic, University of California [San Diego] (UC San Diego), 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), National Institutes of Health [Bethesda] (NIH), National Cancer Institute [Bethesda] (NCI-NIH), Sharp Memorial Hospital [San Diego, CA, USA] (SMH), and CarMeN, laboratoire
Subjects: nonalcoholic fatty liver disease, Adult, Liver Cirrhosis, Hepatology, cirrhosis, [SDV]Life Sciences [q-bio], Biopsy, Gastroenterology, Fibrosis, Article, [SDV] Life Sciences [q-bio], Cross-Sectional Studies, noninvasive assessment, Liver, Non-alcoholic Fatty Liver Disease, Clinical Decision Rules, Elasticity Imaging Techniques, Humans, Pharmacology (medical), Female
Abstract: International audience; BACKGROUND AND AIMS: Patients with nonalcoholic fatty liver disease (NAFLD) cirrhosis benefit from referral to subspecialty care. While several clinical prediction rules exist to identify advanced fibrosis, the cutoff for excluding cirrhosis due to NAFLD is unclear. This analysis compared clinical prediction rules for excluding biopsy-proven cirrhosis in NAFLD. METHODS: Adult patients were enrolled in the NASH Clinical Research Network (US) and the Newcastle Cohort (UK). Clinical and laboratory data were collected at enrolment, and a liver biopsy was taken within 1 year of enrolment. Optimal cutoffs for each score (eg, FIB-4) to exclude cirrhosis were derived from the US cohort, and sensitivity, specificity, positive predictive value, negative predictive value and AUROC were calculated. The cutoffs were evaluated in the UK cohort. RESULTS: 147/1483 (10%) patients in the US cohort had cirrhosis. All prediction rules had similarly high NPV (0.95-0.97). FIB-4 and NAFLD fibrosis scores were the most accurate in characterising patients as having cirrhosis (AUROC 0.84-0.86). 59/494 (12%) patients in the UK cohort had cirrhosis. Prediction rules had high NPV (0.92-0.96), and FIB-4 and NAFLD fibrosis score the most accurate in the prediction of cirrhosis in the UK cohort (AUROC 0.87-0.89). CONCLUSIONS: This cross-sectional analysis of large, multicentre international datasets shows that current clinical prediction rules perform well in excluding cirrhosis with appropriately chosen cutoffs. These clinical prediction rules can be used in primary care to identify patients, particularly those who are white, female, and \textless65, unlikely to have cirrhosis so higher-risk patients maintain access to specialty care.
Published: 2021

188. TAVR Patients Requiring Anticoagulation: Direct Oral Anticoagulant or Vitamin K Antagonist?

Author: Didier, Romain, Lhermusier, Thibault, Auffret, Vincent, Eltchaninoff, Hélène, Le Breton, Herve, Cayla, Guillaume, Commeau, Philippe, Collet, J. P., Cuisset, Thomas, Dumonteil, Nicolas, Verhoye, J. P., Beurtheret, Sylvain, Lefevre, Thierry, Teiger, Emmanuel, Carrié, Didier, Himbert, Dominique, Albat, Bernard, Cribier, Alain, Sudre, Arnaud, Blanchard, Didier, Bar, Olivier, Rioufol, Gilles, Collet, Frédéric, Houel, Remi, Labrousse, Louis, Meneveau, Nicolas, Ghostine, Said, Manigold, Thibaut, Guyon, Philippe, Delepine, Stephane, Favereau, Xavier, Souteyrand, Geraud, Ohlmann, Patrick, Doisy, Vincent, Beygui, Farzin, Gommeaux, Antoine, Claudel, Jean-Philippe, Bourlon, Francois, Bertrand, Bernard, Iung, Bernard, Gilard, Martine, Service de cardiologie [Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Endothélium, valvulopathies et insuffisance cardiaque (EnVI), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU), CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Université de Montpellier (UM), Polyclinique Les Fleurs - ELSAN [Ollioules] (PLF), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital de la Timone [CHU - APHM] (TIMONE), Clinique Pasteur [Toulouse], Service de chirurgie thoracique cardiaque et vasculaire [Rennes] = Thoracic and Cardiovascular Surgery [Rennes], Hôpital Saint-Joseph [Marseille], Sorbonne Université (SU), CHU Henri Mondor [Créteil], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Oto-Rhino-Laryngologie (O.R.L.) et de Chirurgie Cervico-Faciale [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Nouvelle Clinique de Tours Saint Gatien-Alliance [Tours] (CTSGA), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Bordeaux [Bordeaux], Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( UR 3920) (PCVP / CARDIO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Chirurgical Marie Lannelongue (CCML), Service de Cardiologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Max Planck Institute for Chemistry (MPIC), Max-Planck-Gesellschaft, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital privé de Parly 2 - Ramsay Santé [Le Chesnay-Rocquencourt], CHU Clermont-Ferrand, CHU Strasbourg, Médipôle Lyon-Villeurbanne, Hôpital privé de Bois-Bernard - Ramsay Santé [Bois-Bernard], Clinique de l'Infirmerie Protestante de Lyon (CIPL), Centre Cardio-Thoracique de Monaco (CCTM), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Universitaire [Grenoble] (CHU), Service de cardiologie [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot, Sorbonne Paris Cité, Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), ANR-16-RHUS-0003,STOP-AS,STOP-AS(2016), CHU Toulouse [Toulouse], 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), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Service de Cardiologie [CHU Pitié-Salpêtrière], CHU Henri Mondor, Institut des Sciences Chimiques de Rennes (ISCR), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( EA 3920) (PCVP / CARDIO), Centre chirurgical Marie Lannelongue, 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), and CarMeN, laboratoire
Subjects: [SDV] Life Sciences [q-bio], Transcatheter aortic valve replacement, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV]Life Sciences [q-bio], Anticoagulant, Antithrombotic treatment, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Abstract: International audience; OBJECTIVES: Using French transcatheter aortic valve replacement (TAVR) registries linked with the nationwide administrative databases, the study compared the rates of long-term mortality, bleeding, and ischemic events after TAVR in patients requiring oral anticoagulation with direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs). BACKGROUND: The choice of optimal drug for anticoagulation after TAVR remains debated. METHODS: Data from the France-TAVI and FRANCE-2 registries were linked to the French national health single-payer claims database, from 2010 to 2017. Propensity score matching was used to reduce treatment-selection bias. Two primary endpoints were death from any cause (efficacy) and major bleeding (safety). RESULTS: A total of 24,581 patients who underwent TAVR were included and 8,962 (36.4%) were treated with OAC. Among anticoagulated patients, 2,180 (24.3%) were on DOACs. After propensity matching, at 3 years, mortality (hazard ratio [HR]: 1.37; 95% confidence interval [CI]: 1.12-1.67; P \textless 0.005) and major bleeding including hemorrhagic stroke (HR: 1.64; 95% CI: 1.17-2.29; P \textless 0.005) were lower in patients on DOACs compared with those on VKAs. The rates of ischemic stroke (HR: 1.32; 95% CI: 0.81-2.15; P = 0.27) and acute coronary syndrome (HR: 1.17; 95% CI: 0.68-1.99; P = 0.57) did not differ among groups. CONCLUSIONS: In these large multicenter French TAVR registries with an exhaustive clinical follow-up, the long-term mortality and major bleeding were lower with DOACs than VKAs at discharge. The present study supports preferential use of DOACs rather than VKAs in patients requiring oral anticoagulation therapy after TAVR.
Published: 2021

189. A Novel Approach for Managing Protein-Energy Wasting in People With Kidney Failure Undergoing Maintenance Hemodialysis: Rationale and Call for Trials

Author: Team1 Carmen, Carmen Lab, University of Nevada [Reno], Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), and CarMeN, laboratoire
Subjects: [SDV] Life Sciences [q-bio], Nephrology, Renal Dialysis, [SDV]Life Sciences [q-bio], Animals, Humans, Kidney Failure, Chronic, Nutritional Status, Renal Insufficiency, Renal Insufficiency, Chronic, Protein-Energy Malnutrition
Abstract: International audience; Protein-energy wasting (PEW) is a unique presentation of protein-energy malnutrition in people with kidney disease that is characterized by body protein catabolism exceeding anabolism. PEW is especially common in patients undergoing maintenance hemodialysis (HD) treatment. Dietary guidelines for managing PEW in HD patients primarily focus on protein adequacy, and typically promote the intake of animal-based protein foods. Although intake of protein and essential amino acids is important for protein synthesis, the emphasis on protein adequacy largely fails to address, and may actually exacerbate, many of the root causes of PEW. This review examines the dietary determinants of PEW in people undergoing HD treatment, with an emphasis on upstream disease-related factors that reduce dietary protein utilization and impair dietary intakes. From this, we present a theoretical diet model for managing PEW that includes etiology-based dietary strategies to address barriers to intake and treat disease-related factors, as well as supportive dietary strategies to promote adequate energy and protein intakes. Given the complexity of diet-disease interactions in the pathogenesis of PEW, and its ongoing burden in HD patients, interventional trials are urgently needed to evaluate alternative diet therapy approaches for PEW in this population.
Published: 2021

190. 'Donor milk banking: Improving the future'. A survey on the operation of the European donor human milk banks

Author: Kontopodi, Eva, Arslanoglu, Sertac, Bernatowicz-Lojko, Urszula, Bertino, Enrico, Bettinelli, Maria Enrica, Buffin, Rachel, Cassidy, Tanya, van Elburg, Ruurd M, Gebauer, Corina, Grovslien, Anne, Hettinga, Kasper, Ioannou, Ioanna, Klotz, Daniel, Mileusnić-Milenović, Radmila, Moro, Guido E, Picaud, Jean-Charles, Stahl, Bernd, Weaver, Gillian, van Goudoever, Johannes B, Wesolowska, Aleksandra, Afd Chemical Biology and Drug Discovery, Chemical Biology and Drug Discovery, Afd Chemical Biology and Drug Discovery, Chemical Biology and Drug Discovery, Amsterdam UMC - Amsterdam University Medical Center, Wageningen University and Research [Wageningen] (WUR), Istanbul Medeniyet University [Istanbul, Turquie] (IMU), Centre of Postgraduate Medical Education [Warsaw, Poland] (CPME), Human Milk Bank Foundation [Warsaw, Poland] (HMBF), Università degli studi di Torino = University of Turin (UNITO), Maternal and Child Health Unit [Milan, Italy] (MCHU), 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), Dublin City University [Dublin] (DCU), Universitätsklinikum Leipzig [Germany] (UKL), Klinik und Poliklinik für Kinder- und Jugendmedizin [Leipzig, Germany] (KPKJ), Oslo University Hospital [Oslo], Elena Venizelou Maternity Hospital [Athens, Greece] (EVMH), University of Freiburg [Freiburg], Institute of Neonatology [Belgrade, Serbia] (IN), Italian Association of Human Milk Banks [Milan, Italy] (AIBLUD), Danone Nutricia Research [Utrecht], Utrecht University [Utrecht], Medical University of Warsaw - Poland, and CarMeN, laboratoire
Subjects: European level, Physiology, Epidemiology, Staphylococcus, [SDV]Life Sciences [q-bio], Pasteurization, Distribution (economics), Pathology and Laboratory Medicine, law.invention, Geographical Locations, fluids and secretions, law, Surveys and Questionnaires, Medicine and Health Sciences, Staphylococcus Aureus, Socioeconomics, media_common, Multidisciplinary, Donor recruitment, Physics, food and beverages, Milk, Human, Tissue Donors, Milk Banks, Condensed Matter Physics, Body Fluids, Bacterial Pathogens, Europe, [SDV] Life Sciences [q-bio], Serology, Food Quality and Design, Milk, Medical Microbiology, Physical Sciences, Medicine, Anatomy, Pathogens, Phase Transitions, Research Article, Human, Science, media_common.quotation_subject, Detailed data, Thawing, Research and Analysis Methods, Microbiology, Beverages, Life Science, Quality (business), Microbial Pathogens, Nutrition, VLAG, Pharmacology, Drug Screening, Bacteria, business.industry, Organisms, Biology and Life Sciences, Diet, Milk banking, Storage and Handling, Medical Risk Factors, People and Places, business
Abstract: Background Provision of donor human milk is handled by established human milk banks that implement all required measures to ensure its safety and quality. Detailed human milk banking guidelines on a European level are currently lacking, while the information available on the actual practices followed by the European human milk banks, remains limited. The aim of this study was to collect detailed data on the actual milk banking practices across Europe with particular emphasis on the practices affecting the safety and quality of donor human milk. Materials and methods A web-based questionnaire was developed by the European Milk Bank Association (EMBA) Survey Group, for distribution to the European human milk banks. The questionnaire included 35 questions covering every step from donor recruitment to provision of donor human milk to each recipient. To assess the variation in practices, all responses were then analyzed for each country individually and for all human milk banks together. Results A total of 123 human milk banks completed the questionnaire, representing 85% of the European countries that have a milk bank. Both inter- and intra-country variation was documented for most milk banking practices. The highest variability was observed in pasteurization practices, storage and milk screening, both pre- and post-pasteurization. Conclusion We show that there is a wide variability in milk banking practices across Europe, including practices that could further improve the efficacy of donor human milk banking. The findings of this study could serve as a tool for a global discussion on the efficacy and development of additional evidence-based guidelines that could further improve those practices.
Published: 2021

191. Therapeutic Hypothermia Reduces Peritoneal Dialysis Induced Myocardial Blood Flow Heterogeneity and Arrhythmia

Author: Sanjay R. Kharche, Sandrine Lemoine, Tanya Tamasi, Lisa Hur, Aaron So, Christopher W. McIntyre, CarMeN, laboratoire, Victoria hospital, University of Western Ontario (UWO), Lawson Health Research Institute, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Medicine (General), medicine.medical_specialty, [SDV]Life Sciences [q-bio], medicine.medical_treatment, 030232 urology & nephrology, therapeutic hypothermia, 030204 cardiovascular system & hematology, arrhythmia, Peritoneal dialysis, 03 medical and health sciences, R5-920, 0302 clinical medicine, Peritoneum, Internal medicine, medicine, computed tomography imaging, The authors declare that the research was conducted in the absence of any commercial, Dialysis, Original Research, business.industry, General Medicine, Blood flow, Hypothermia, [SDV] Life Sciences [q-bio], Regimen, medicine.anatomical_structure, interest, peritoneal dialysis, or financial relationships that could be construed as a potential conflict of, Ventricle, Cardiology, Medicine, medicine.symptom, business, Perfusion, computational cardiology
Abstract: Background: Moderate therapeutic hypothermia (TH) is a well-recognized cardio-protective strategy. The instillation of fluid into the peritoneum provides an opportunity to deliver moderate hypothermia as primary prevention against cardiovascular events. We aimed to to investigate both cardiac perfusion consequences (overall blood flow and detailed assessment of perfusion heterogeneity) and subsequently simulate the associated arrhythmic risk for patients undergoing peritoneal dialysis (PD) induced TH.Methods: Patients underwent high resolution myocardial perfusion scanning using high resolution 256 slice CT scanning, at rest and with adenosine stress. The first visit using the patient's usual PD regimen, on the second visit the same regime was utilized but with cooled peritoneal dialysate at 32°C. Myocardial blood flow (MBF) was quantified from generated perfusion maps, reconstructed in 3D. MBF heterogeneity was assessed by fractal dimension (FD) measurement on the 3D left ventricular reconstruction. Arrhythmogenicity was quantified from a sophisticated computational simulation using a multi-scale human 3D ventricle wedge electrophysiological computational model.Results: We studied 7 PD patients, mean age of 60 ± 7 and mean vintage dialysis of 23.6 ± 17.6 months. There were no significant different in overall segmental MBF between normothermic condition (NT) and TH. MBF heterogeneity was significantly decreased (−14%, p = 0.03) at rest and after stress (−14%, p = 0.03) when cooling was applied. Computational simulation showed that TH allowed a normalization of action potential, QT duration and T wave.Conclusion: TH-PD results in moderate hypothermia leading to a reduction in perfusion heterogeneity and simulated risk of non-terminating malignant ventricular arrhythmias.
Published: 2021

192. A systematic review and meta‐analyses of food preference modifications after bariatric surgery

Author: Sarah Bagot, Emmanuel Disse, Erika Guyot, Julie-Anne Nazare, Sylvain Iceta, Anestis Dougkas, Centre Européen Nutrition et Santé [Pierre-Bénite] (CENS/CRNH-RA), Centre de Recherche en Nutrition Humaine Rhône Alpes (CRNH Rhône Alpes), Centre de Recherche de l'Institut Paul Bocuse [Ecully] (CRIPB), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Institut Universitaire de Cardiologie et de Pneumologie de Québec (IUCPQ), Université Laval [Québec] (ULaval), and CarMeN, laboratoire
Subjects: Sleeve gastrectomy, medicine.medical_specialty, bariatric surgery, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Gastric bypass, Gastric Bypass, MEDLINE, CINAHL, Cochrane Library, Food preference, Food Preferences, Gastrectomy, Food choice, medicine, Humans, business.industry, Public Health, Environmental and Occupational Health, Obesity, Morbid, Surgery, [SDV] Life Sciences [q-bio], food reward, food choices, Observational study, food preference, business
Abstract: International audience; This systematic review and meta-analyses aimed to synthesize evidence of the link between bariatric surgery and changes in food preferences, considering the method of assessment. MEDLINE, Cochrane Library, Web of Science, Cinahl, PsychINFO, ProQuest, and Open grey were searched incorporating two blocks of terms ("Intervention" and "Food Preferences"). Interventional or observational studies involving patients (BMI ≥ 35 kg m(-2) ) with sleeve gastrectomy (SG) or Roux-en-Y Gastric Bypass (RYGB) and a control group were included. Meta-analyses were performed comparing the standardized daily mean percentage energy from proteins, carbohydrates, and lipids between preoperative and postoperative patients. Fifty-seven studies concerning 2,271 patients with RYGB and 903 patients with SG met the inclusion criteria, of which 24 were eligible for meta-analysis. Despite a total reduction in macronutrient intakes, the meta-analyses revealed a postoperative increase in percentage energy from proteins at 12 months (0.24, 95% CI: 0.03, 0.46, \I(2) \ = 73%) and a decrease in percentage energy from fat at 1 month (-0.47, 95% CI: 0.86, 0.09, \I(2) \ = 72%), up to 24 months (-0.20, 95% CI: -0.31, 0.08, \I(2) \ = 0%). In conclusion, the present systematic review and meta-analyses showed changes of food preferences in terms of macronutrient, food selection and, overall food appreciation up to 5 years following bariatric surgery.
Published: 2021

193. Risk factors associated with day-30 mortality in patients over 60 years old admitted in ICU for severe COVID-19: the Senior-COVID-Rea Multicentre Survey protocol

Author: Claire, Falandry, Amélie, Malapert, Mélanie, Roche, Fabien, Subtil, Julien, Berthiller, Camille, Boin, Justine, Dubreuil, Christine, Ravot, Laurent, Bitker, Paul, Abraham, Vincent, Collange, Baptiste, Balança, Sylvie, Goutte, Céline, Guichon, Emilie, Gadea, Laurent, Argaud, David, Dayde, Laurent, Jallades, Alain, Lepape, Jean-Baptiste, Pialat, Arnaud, Friggeri, Fabrice, Thiollière, Marine, Thieux, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Université de Lyon, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Délégation à la Recherche Clinique et à l'Innovation [Lyon] (DRCI), Hôpital de la Croix-Rousse [CHU - HCL], Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Edouard Herriot [CHU - HCL], Médipôle Lyon-Villeurbanne, Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), L'Hôpital Nord-Ouest [Villefranche sur Saône], Centre Hospitalier Emile Roux [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'anesthésie-réanimation [Centre Hospitalier Lyon Sud - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Senior-COVID-Rea study Group: Christophe Leroy, Anne-Claire Lukaszewicz, Thomas Rimmelé, Marie Simon, Charles-Hervé Vacheron, Hodane Yonis, Antoine Garnier-Crussard, Max Haïne, Loredana Baboi, Camille Boin, Valérie Cerro, David Dayde, Justine Dubreuil, Carlos El Khoury, Emilie Gadéa-Deschamps, Marie-Catherine Fromont, Audrey Gelot, Anthéa Loïez, Amélie Malapert, Céline Monard, Maya Perrou, Laetitia Paradisi-Prieur, Marion Provent, Mélanie Roche, Gulsum Sahin, Ghyslaine Thao, Marine Thieux., Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CarMeN, laboratoire, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie (CIRI), and École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL)
Subjects: intensive & critical care, SARS-CoV-2, geriatric medicine, [SDV]Life Sciences [q-bio], Intensive Care, COVID-19, Middle Aged, [SDV] Life Sciences [q-bio], Intensive Care Units, Risk Factors, Surveys and Questionnaires, Prohibitins, Humans, Multicenter Studies as Topic, France, Aged
Abstract: International audience; INTRODUCTION: With the spread of COVID-19 epidemic, health plans must be adapted continuously. There is an urgent need to define the best care courses of patients with COVID-19, especially in intensive care units (ICUs), according to their individualised benefit/risk ratio. Since older age is associated with poorer short-term and long-term outcomes, prediction models are needed, that may assist clinicians in their ICU admission decision. Senior-COVID-Rea was designed to evaluate, in patients over 60 years old admitted in ICU for severe COVID-19 disease, the impact of age and geriatric and paraclinical parameters on their mortality 30 days after ICU admission. METHODS AND ANALYSIS: This is a multicentre survey protocol to be conducted in seven hospitals of the Auvergne-Rhône-Alpes region, France. All patients over 60 years old admitted in ICU for severe COVID-19 infection (or their legally acceptable representative) will be proposed to enter the study and to fill in a questionnaire regarding their functional and nutritional parameters 1 month before COVID-19 infection. Paraclinical parameters at ICU admission will be collected: lymphocytes and neutrophils counts, high-fluorescent lymphoid cells and immature granulocytes percentages (Sysmex data), D-dimers, C-reactive protein, lactate dehydrogenase (LDH), creatinine, CT scan for lung extension rate as well as clinical resuscitation scores, and the delay between the first signs of infection and ICU admission. The primary outcome will be the overall survival at day 30 post-ICU admission. The analysis of factors predicting mortality at day 30 will be carried out using univariate and multivariate logistic regressions. Multivariate logistic regression will consider up to 15 factors.The ambition of this trial, which takes into account the different approaches of geriatric vulnerability, is to define the respective abilities of different operational criteria of frailty to predict patients' outcomes. ETHICS AND DISSEMINATION: The study protocol was ethically approved. The results of the primary and secondary objectives will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04422340.
Published: 2021

194. NLRC4 GOF Mutations, a Challenging Diagnosis from Neonatal Age to Adulthood

Author: Juliette Bardet, Noémie Laverdure, Mathieu Fusaro, Capucine Picard, Lorna Garnier, Sébastien Viel, Sophie Collardeau-Frachon, Jean-Marie De Guillebon, Isabelle Durieu, Clémence Casari-Thery, Guillaume Mortamet, Audrey Laurent, Alexandre Belot, Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de référence des rhumatismes inflammatoires et maladies autoimmunes systémiques rares de l'enfant [Hôpital Femme Mère Enfant, HCL] (RAISE), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Lyon Immunopathology Federation (LIFe), 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), Université de Lyon, Service de chirurgie pédiatrique [CHU Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), CarMeN, laboratoire, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV] Life Sciences [q-bio], sepsis, NLRC4, inflammasome, [SDV]Life Sciences [q-bio], Medicine, autoinflammatory diseases, allergy, Article, inflammasomopathy
Abstract: The NLRC4 inflammasome is part of the human immune innate system. Its activation leads to the cleavage of pro-inflammatory cytokines IL-1β and IL-18, promoting inflammation. NLRC4 gain-of-function (GOF) mutations have been associated with early-onset recurrent fever, recurrent macrophagic activation syndrome and enterocolitis. Herein, we describe two new patients with NLRC4 mutations. The first case presented with recurrent fever and vasoplegic syndrome, gut symptoms and urticarial rashes initially misdiagnosed as a severe protein-induced enterocolitis syndrome. The second case had recurrent macrophage activation syndrome (MAS) and shock, suggesting severe infection. We identified two NLRC4 mutations, on exon 4, within the nucleotide-binding protein domain (NBD). After a systematic review of NLRC4 GOF mutations, we highlight the wide spectrum of this disease with a limited genotype–phenotype correlation. Vasoplegic shock was only reported in patients with mutation in the NBD. Diagnosing this new entity combined with gastrointestinal symptoms and vasoplegic shocks is challenging. It mimics severe allergic reaction or sepsis. The plasma IL-18 level and genetic screening are instrumental to make a final diagnosis.
Published: 2021

195. Classification of Uremic Toxins and Their Role in Kidney Failure

Author: Manish Kaushik, Peter Stenvinkel, Kianoush Kashani, Ziad A. Massy, Li Zuo, Faeq Husain-Syed, Thiago Reis, Peter J. Blankestijn, Hideki Kawanishi, Colin A. Hutchison, Raymond Vanholder, Laurent Juillard, Claudio Ronco, Mario Cozzolino, Mitchell H. Rosner, Tammy L. Sirich, University of Virginia [Charlottesville], University of Brasilia [Brazil] (UnB), Justus-Liebig-University [Gießen, Germany], Ghent University Hospital, University of Southern Queensland (USQ), Hawke's Bay District Health Board [Hastings, New Zealand], Karolinska Institutet [Stockholm], University Medical Center [Utrecht], University of Milan, Università degli Studi di Milano [Milano] (UNIMI), 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 Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Université de Lyon, Mayo Clinic [Rochester], National University Hospital [Singapore] (NUH), Tsuchiya General Hospital [Hiroshima, Japan] (TGH), Hôpital Ambroise Paré [AP-HP], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), 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, Veterans Affairs Palo Alto Health Care System [Palo Alto, CA, USA], Stanford University, People's Hospital of Peking University (PEKING - PHPU), Peking University [Beijing], University of Padova Medical School, International Renal Research Institute [Vicenza, Italy] (I2RI), University of Virginia, Justus-Liebig-Universität Gießen = Justus Liebig University (JLU), Università degli Studi di Milano = University of Milan (UNIMI), People's Hospital of Peking University (PKUPH), Università degli Studi di Padova = University of Padua (Unipd), and CarMeN, laboratoire
Subjects: medicine.medical_specialty, Epidemiology, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Reviews, Classification scheme, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, 03 medical and health sciences, 0302 clinical medicine, Medicine, definition, In patient, Intensive care medicine, Dialysis, uremia, Transplantation, business.industry, Consensus conference, medicine.disease, Uremia, 3. Good health, middle molecule, [SDV] Life Sciences [q-bio], classification, Nephrology, Uremic toxins, dialysis, Hemodialysis, business, Middle molecule
Abstract: International audience; Advances in our understanding of uremic retention solutes, and improvements in hemodialysis membranes and other techniques designed to remove uremic retention solutes, offer opportunities to readdress the definition and classification of uremic toxins. A consensus conference was held to develop recommendations for an updated definition and classification scheme on the basis of a holistic approach that incorporates physicochemical characteristics and dialytic removal patterns of uremic retention solutes and their linkage to clinical symptoms and outcomes. The major focus is on the removal of uremic retention solutes by hemodialysis. The identification of representative biomarkers for different classes of uremic retention solutes and their correlation to clinical symptoms and outcomes may facilitate personalized and targeted dialysis prescriptions to improve quality of life, morbidity, and mortality. Recommendations for areas of future research were also formulated, aimed at improving understanding of uremic solutes and improving outcomes in patients with CKD.
Published: 2021

196. Cardiometabolic impacts of saturated fatty acids: are they all comparable?

Author: Aline Maria Nunes de Lira Gomes Bloise, João Henrique Costa-Silva, Aiany C. Simões-Alves, Alves Debora Santos, Béatrice Morio, Universidade Federal Rural de Pernambuco (UFRPE), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and CarMeN, laboratoire
Subjects: obesity, [SDV]Life Sciences [q-bio], 030209 endocrinology & metabolism, 03 medical and health sciences, 0302 clinical medicine, nutrition transition, Environmental health, medicine, Nutrition transition, Humans, Saturated fatty acids, Total energy, 030304 developmental biology, 2. Zero hunger, Carbon chain, 0303 health sciences, High prevalence, business.industry, Fatty Acids, dyslipidemia, food and beverages, medicine.disease, Food safety, Dietary Fats, Obesity, Diet, 3. Good health, [SDV] Life Sciences [q-bio], Cardiovascular Diseases, cardiometabolic, Energy Intake, business, Dyslipidemia, Food Science
Abstract: International audience; In last decades, a phenomenon named nutrition transition has been observed in many countries around the world. It has been characterised by increased consumption of fat-rich diets, predisposing to cardiometabolic diseases and high prevalence of the obesity. In the dietary recommendations cited to prevent metabolic diseases, there is a consensus to decrease intake of saturated fatty acids (SFA) to less than 10% of total energy intake, as recommended by the Food Safety Authorities. However, fatty acids of different chain lengths may exhibit different cardiometabolic effects. Thus, our major aim was to review the cardiometabolic effects of different classes of SFA according to carbon chain length, i.e. short-, medium- and long-chains. The review emphasises that not all SFA may have harmful cardiometabolic effects since short- and medium-chain SFA can provide beneficial health effects and participate to the prevention of metabolic disorders.
Published: 2021

197. Influence of stroke infarct location on quality of life assessed in a multivariate lesion-symptom mapping study

Author: Christian Gerloff, Robin Lemmens, Keith W. Muir, Alina Königsberg, Matthias Endres, Josep Puig, Jochen B. Fiebach, Salvador Pedraza, Norbert Nighoghossian, Bastian Cheng, Vincent Thijs, Eckhard Schlemm, Claus Z Simonsen, Andrew T. DeMarco, Götz Thomalla, Tae-Hee Cho, Jens Fiehler, Ivana Galinovic, Martin Ebinger, Carola Mayer, Anke Wouters, Neurology, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Georgetown University [Washington] (GU), VU University Medical Center [Amsterdam], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Girona Biomedical Research Institute [Girona, Spain] (IDIBGI), Austin Health, University of Melbourne, University Hospitals Leuven [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Campus Gasthuisberg, University of Glasgow, Aarhus University Hospital, Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and CarMeN, laboratoire
Subjects: Male, Multivariate statistics, IMPACT, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, 0302 clinical medicine, Quality of life, Stroke, Multidisciplinary, medicine.diagnostic_test, Brain, Human brain, Middle Aged, RECOVERY, HUMAN BRAIN, Magnetic Resonance Imaging, [SDV] Life Sciences [q-bio], Multidisciplinary Sciences, medicine.anatomical_structure, Neurology, Medicine, Science & Technology - Other Topics, Female, medicine.symptom, Brain Infarction, medicine.medical_specialty, Science, Article, Lesion, White matter, 03 medical and health sciences, Medical research, Double-Blind Method, Internal medicine, medicine, Humans, Aged, Science & Technology, business.industry, DISABILITY, Magnetic resonance imaging, medicine.disease, Clinical research, Quality of Life, business, 030217 neurology & neurosurgery, SYSTEM, Neuroscience
Abstract: Conflict of interest statementAK reports grants from European Union 7th Framework Program during the conduct of the study. ADM has nothing to disclose. CM has nothing to disclose. AW has nothing to disclose. ES has nothing to disclose. ME reports grants from European Union 7th Framework Program during the conduct of the study. THC has nothing to disclose. MEn reports grants from European Union 7th Framework Program during the conduct of the study, grants from Bayer and fees paid to the Charité from Bayer, Boehringer Ingelheim, BMS/Pfizer, Daiichi Sankyo, Amgen, GlaxoSmithKlineGSK, Sanofi, Covidien, Novartis, all outside the submitted work. JBF reports grants from European Union 7th Framework Program during the conduct of the study and personal fees from Bioclinica, BMS, Biogen, Artemida, Cerevast, Guerbet, EISAI and Nicolab outside the submitted work. JF has nothing to disclose. IG reports grants from European Union 7th Framework Program during the conduct of the study. JP has nothing to disclose. VT reports grants from European Union 7th Framework Program and personal fees and non-financial support from Boehringer Ingelheim, Pfizer/BMS, Bayer, Sygnis, Amgen and Allergan outside the submitted work. RL reports no personal fees, but institutional support for consultancy and speaker fees from Bayer, Boehringer-Ingelheim, Genentech, Ischemaview, Medtronic and Occlutech outside the submitted work. KWM reports grants from European Union 7th Framework Program during the conduct of the study, personal fees and non-financial support from Boehringer Ingelheim outside the submitted work, personal fees from Boehringer Ingelheim, Bayer, Daiichi Sankyo and ReNeuron outside the submitted work. NN has nothing to disclose. SP reports grants from European Union 7th Framework Program during the conduct of the study. CZS reports grants from Novo Nordisk Foundation and personal fees from Bayer outside the submitted work. CG reports grants from European Union 7th Framework Program during the conduct of the study, personal fees from AMGEN, Bayer Vital, BMS, Boehringer Ingelheim, Sanofi Aventis, Abbott, and Prediction Biosciences outside the submitted work. GT reports grants from European Union 7th Framework Program during the conduct of the study, personal fees from Acandis, Boehringer Ingelheim, BMS/Pfizer, Stryker, Daiichi Sankyo, grants and personal fees from Bayer, grants from Corona Foundation, German Innovation Fonds and Else Kroener Fresenius Foundation outside the submitted work. BC reports grants from European Union 7th Framework Program during the conduct of the study and personal fees from Bayer Vital and Abbott, all outside the submitted work.; International audience; Stroke has a deleterious impact on quality of life. However, it is less well known if stroke lesions in different brain regions are associated with reduced quality of life (QoL). We therefore investigated this association by multivariate lesion-symptom mapping. We analyzed magnetic resonance imaging and clinical data from the WAKE-UP trial. European Quality of Life 5 Dimensions (EQ-5D) 3 level questionnaires were completed 90 days after stroke. Lesion symptom mapping was performed using a multivariate machine learning algorithm (support vector regression) based on stroke lesions 22-36 h after stroke. Brain regions with significant associations were explored in reference to white matter tracts. Of 503 randomized patients, 329 were included in the analysis (mean age 65.4 years, SD 11.5; median NIHSS = 6, IQR 4-9; median EQ-5D score 90 days after stroke 1, IQR 0-4, median lesion volume 3.3 ml, IQR 1.1-16.9 ml). After controlling for lesion volume, significant associations between lesions and EQ-5D score were detected for the right putamen, and internal capsules of both hemispheres. Multivariate lesion inference analysis revealed an association between injuries of the cortico-spinal tracts with worse self-reported quality of life 90 days after stroke in comparably small stroke lesions, extending previous reports of the association of striato-capsular lesions with worse functional outcome. Our findings are of value to identify patients at risk of impaired QoL after stroke.
Published: 2021

198. Barriers to conservative care from patients' and nephrologists' perspectives: the CKD-REIN study

Author: Aghilès, Hamroun, Elodie, Speyer, Carole, Ayav, Christian, Combe, Denis, Fouque, Christian, Jacquelinet, Maurice, Laville, Sophie, Liabeuf, Ziad A, Massy, Roberto, Pecoits-Filho, Bruce M, Robinson, François, Glowacki, Bénédicte, Stengel, Luc, Frimat, 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, Service de Néphrologie et Transplantation rénale [CHRU-lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Epidémiologie et Evaluations Cliniques [CHRU Nancy] (Pôle S2R), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Bioingénierie tissulaire (BIOTIS), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Agence de la biomédecine [Saint-Denis la Plaine], Université Paris-Saclay, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), CHU Amiens-Picardie, Université de Picardie Jules Verne (UPJV), Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Chronic Kidney Disease - Réseau Epidémiologie et Information en Néphrologie (CKD REIN), Institut National de la Santé et de la Recherche Médicale (INSERM), Épidémiologie et recherches translationnelles sur les maladies rénales et cardiovasculaires (EPREC) (U1018 (Équipe 5)), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Service Néphrologie/Dialyse [AP-HP Ambroise-Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Arbor Research Collaborative for Health, Service de Néphrologie [CHRU Nancy], Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), Université de Lorraine (UL), CKD-REIN study: Natalia Alencar de Pinho, Carole Ayav, Serge Briançon, Dorothée Cannet, Christian Combe, Denis Fouque, Luc Frimat, Yves-Edouard Herpe, Christian Jacquelinet, Maurice Laville, Ziad A Massy, Christophe Pascal, Bruce M Robinson, Bénédicte Stengel, Céline Lange, Karine Legrand, Sophie Liabeuf, Marie Metzger, Elodie Speyer, Thierry Hannedouche, Bruno Moulin, Sébastien Mailliez, Gaétan Lebrun, Eric Magnant, Gabriel Choukroun, Benjamin Deroure, Adeline Lacraz, Guy Lambrey, Jean Philippe Bourdenx, Marie Essig, Thierry Lobbedez, Raymond Azar, Hacène Sekhri, Mustafa Smati, Mohamed Jamali, Alexandre Klein, Michel Delahousse, Christian Combe, Séverine Martin, Isabelle Landru, Eric Thervet, Ziad A Massy, Philippe Lang, Xavier Belenfant, Pablo Urena, Carlos Vela, Luc Frimat, Dominique Chauveau, Victor Panescu, Christian Noel, François Glowacki, Maxime Hoffmann, Maryvonne Hourmant, Dominique Besnier, Angelo Testa, François Kuentz, Philippe Zaoui, Charles Chazot, Laurent Juillard, Stéphane Burtey, Adrien Keller, Nassim Kamar, Denis Fouque, Maurice Laville, and CarMeN, laboratoire
Subjects: conservative care, Transplantation, [SDV]Life Sciences [q-bio], Conservative Treatment, kidney failure, supportive care, [SDV] Life Sciences [q-bio], Nephrologists, Renal Replacement Therapy, Nephrology, comprehensive conservative care, Surveys and Questionnaires, Humans, Renal Insufficiency, Chronic, chronic kidney disease, Aged
Abstract: Background Conservative care is increasingly considered an alternative to kidney replacement therapy for kidney failure management, mostly among the elderly. We investigated its status and the barriers to its implementation from patients’ and providers’ perspectives. Methods We analysed data from 1204 patients with advanced chronic kidney disease (CKD) [estimated glomerular filtration rate (eGFR) Results All participating facilities reported they were routinely able to offer conservative care, but only 37% had written protocols and only 5% had a person or team primarily responsible for it. Overall, 6% of patients were estimated to use conservative care. Among nephrologists, 82% reported they were fairly or extremely comfortable discussing conservative care, but only 28% usually or always offered this option for older (>75 years) patients approaching kidney failure. They used various terminology for this care, with conservative management and non-dialysis care mentioned most often. Among patients, 5% of those >75 years reported receiving information about this option and 2% preferring it. Conclusions Although reported by nephrologists to be widely available and easily discussed, conservative care is only occasionally offered to older patients, most of whom report they were not informed of this option. The lack of a person or team responsible for conservative care and unclear information appear to be key barriers to its implementation.
Published: 2021

199. Effect of intravenous alteplase on post-stroke depression in the WAKE UP trial

Author: Bastian Cheng, Salvador Pedraza, Keith W. Muir, Florent Boutitie, Matthias Endres, Alina Königsberg, Robin Lemmens, Sönke Arlt, Susanne Sehner, Christian Gerloff, Jochen B. Fiebach, Claus Z Simonsen, Vincent Thijs, Götz Thomalla, Martin Ebinger, Norbert Nighoghossian, Joaquín Serena, CarMeN, laboratoire, University Hospital Hamburg-Eppendorf, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Evangelisches Krankenhaus Alsterdorf [Hamburg, Germany] (EKA), Aarhus University Hospital, Hospices Civils de Lyon (HCL), Girona Biomedical Research Institute [Girona, Spain] (IDIBGI), Austin Health, University of Melbourne, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], University Hospitals Leuven [Leuven], Vesalius Research Center [Louvain, Belgique], University of Glasgow, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and WAKE-UP investigators
Subjects: [SDV]Life Sciences [q-bio], WAKE-UP, Dwi, DWI, Brain Ischemia, 0302 clinical medicine, Modified Rankin Scale, therapeutic use [Fibrinolytic Agents], Medicine, complications [Stroke], 030212 general & internal medicine, drug therapy [Depression], Transient ischemic attack, Stroke, Cerebral ischemia -- Treatment, Depression, Atac isquèmic transitori, 3. Good health, drug therapy [Stroke], [SDV] Life Sciences [q-bio], Treatment Outcome, Neurology, Tissue Plasminogen Activator, drug therapy [Brain Ischemia], Life Sciences & Biomedicine, psychological phenomena and processes, Mri, MRI, medicine.medical_specialty, etiology [Depression], Clinical Neurology, Placebo, 03 medical and health sciences, Fibrinolytic Agents, Internal medicine, Post-hoc analysis, mental disorders, Post-stroke depression, Humans, ddc:610, WAKE&#8208, UP, Science & Technology, business.industry, Beck Depression Inventory, Neurosciences, Odds ratio, medicine.disease, Wake-up, nervous system, Isquèmia cerebral -- Tractament, Neurology (clinical), Neurosciences & Neurology, business, 030217 neurology & neurosurgery, Fibrinolytic agent
Abstract: BACKGROUND AND PURPOSE: The aim was to study the effect of intravenous alteplase on the development of post-stroke depression (PSD) in acute stroke patients, and to identify predictors of PSD. METHODS: This post hoc analysis included patients with unknown onset stroke randomized to treatment with alteplase or placebo in the WAKE-UP trial (ClinicalTrials.gov number, NCT01525290), in whom a composite end-point of PSD was defined as a Beck Depression Inventory ≥10, medication with an antidepressant, or depression recorded as an adverse event. Multiple logistic regression was used to identify predictors of PSD at 90 days. Structural equation modelling was applied to assess the indirect effect of thrombolysis on PSD mediated by the modified Rankin Scale. RESULTS: Information on the composite end-point was available for 438 of 503 randomized patients. PSD was present in 96 of 224 (42.9%) patients in the alteplase group and 115 of 214 (53.7%) in the placebo group (odds ratio 0.63; 95% confidence interval 0.43-0.94; p = 0.022; adjusted for age and National Institutes of Health Stroke Scale at baseline). Prognostic factors associated with PSD included baseline medication with antidepressants, higher lesion volume, history of depression and assignment to placebo. While 65% of the effect of thrombolysis on PSD were caused directly, 35% were mediated by an improvement of the mRS. CONCLUSIONS: Treatment with alteplase in patients with acute stroke resulted in lower rates of depression at 90 days, which were only partially explained by reduced functional disability. Predictors of PSD including history and clinical characteristics may help in identifying patients at risk of PSD. ispartof: EUROPEAN JOURNAL OF NEUROLOGY vol:28 issue:6 pages:2017-2025 ispartof: location:England status: published
Published: 2021

200. Efficacy and Safety of First-line Single-Agent Carboplatin vs Carboplatin plus Paclitaxel for Vulnerable Older Adult Women with Ovarian Cancer:A GINECO/GCIG Randomized Clinical Trial

Author: Frédérique Rousseau, Olivier Tredan, E. Malaurie, Aude-Marie Savoye, Pierre-Emmanuel Brachet, Claire Falandry, Jørn Herrstedt, Robert Sverdlin, Laurence Venat-Bouvet, Eric Pujade-Lauraine, Emmanuelle Bourbouloux, Alain Lortholary, Fabien Tinquaut, Loic Mourey, Gilles Freyer, Véronique D'Hondt, Marie-Ange Mouret-Reynier, Laetitia Stefani, Alain Zannetti, Domenica Lorusso, 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), Groupe d'Investigateurs Nationaux pour l'Étude des Cancers de l'Ovaire et du sein [Paris] (GINECO), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), IRCCS Istituto Nazionale dei Tumori [Milano], Zealand University Hospital [Roskilde, Denmark], Institut Jean Godinot [Reims], Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], CRLCC René Gauducheau, Centre hospitalier Saint-Joseph [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut du Cancer de Montpellier (ICM), Hôpital privé du Confluent [Nantes], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier de Cholet (CHC), Centre Hospitalier Intercommunal de Créteil (CHIC), Hôpital Dupuytren [CHU Limoges], Centre Léon Bérard [Lyon], Institut Claudius Regaud, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), and CarMeN, laboratoire
Subjects: Cancer Research, medicine.medical_specialty, Combination therapy, medicine.medical_treatment, [SDV]Life Sciences [q-bio], law.invention, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, Interquartile range, law, Internal medicine, Medicine, Data monitoring committee, 030212 general & internal medicine, Chemotherapy, business.industry, Chemotherapy regimen, Carboplatin, 3. Good health, Discontinuation, [SDV] Life Sciences [q-bio], Oncology, chemistry, 030220 oncology & carcinogenesis, business
Abstract: Importance: Single-agent carboplatin is often proposed instead of a conventional carboplatin-paclitaxel doublet in vulnerable older patients with ovarian cancer. Such an approach could have a detrimental effect on outcomes for these patients. Objective: To compare the feasibility, efficacy, and safety of single-agent carboplatin every 3 weeks, weekly carboplatin-paclitaxel, or conventional every-3-weeks carboplatin-paclitaxel in vulnerable older patients with ovarian cancer. Design, Setting, and Participants: This international, open-label, 3-arm randomized clinical trial screened 447 women 70 years and older with newly diagnosed stage III/IV ovarian cancer by determining their Geriatric Vulnerability Score; 120 patients with a Geriatric Vulnerability Score of 3 or higher were stratified by country and surgical outcome. Enrollment took place at 48 academic centers in France, Italy, Finland, Denmark, Sweden, and Canada from December 11, 2013, to April 26, 2017. Final analysis database lock April 2019. Data analysis was performed from February 1 to December 31, 2019. Interventions: Patients were randomized to receive 6 cycles of (1) carboplatin, area under the curve (AUC) 5 mg/mL·min, plus paclitaxel, 175 mg/m 2, every 3 weeks; (2) single-agent carboplatin, AUC 5 mg/mL·min or AUC 6 mg/mL·min, every 3 weeks; or (3) weekly carboplatin, AUC 2 mg/mL·min, plus paclitaxel, 60 mg/m 2, on days 1, 8, and 15 every 4 weeks. Main Outcomes and Measures: The primary outcome was treatment feasibility, defined as the ability to complete 6 chemotherapy cycles without disease progression, premature toxic effects-related treatment discontinuation, or death. Results: A total of 120 women were randomized. The mean and median age was 80 (interquartile range, 76-83; range, 70-94) years; 43 (36%) had a Geriatric Vulnerability Score of 4 and 13 (11%) had a Geriatric Vulnerability Score of 5; 40 (33%) had stage IV disease. During its third meeting, the independent data monitoring committee's recommendation led to the termination of the trial because single-agent carboplatin was associated with significantly worse survival. Six cycles were completed in 26 of 40 (65%), 19 of 40 (48%), and 24 of 40 (60%) patients in the every-3-weeks combination, single-agent carboplatin, and weekly combination groups, respectively. Treatment-related adverse events were less common with the standard every-3-weeks combination (17 of 40 [43%]) than single-agent carboplatin or weekly combination therapy (both 23 of 40 [58%]). Treatment-related deaths occurred in 4 patients (2 of 40 [5%] in each combination group). Conclusions and Relevance: This randomized clinical trial shows that compared with every-3-weeks or weekly carboplatin-paclitaxel regimens, single-agent carboplatin was less active with significantly worse survival outcomes in vulnerable older patients with ovarian cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT02001272.
Published: 2021

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