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1. Exploration of fMRI brain responses to oral sucrose after Roux-en-Y gastric bypass in obese yucatan minipigs in relationship with microbiota and metabolomics profiles

Author: Damien Bergeat, Nicolas Coquery, Yentl Gautier, Sarah Clotaire, Émilie Vincent, Véronique Romé, Sylvie Guérin, Isabelle Le Huërou-Luron, Sophie Blat, Ronan Thibault, David Val-Laillet, Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Chirurgie Hépatobiliaire et Digestive [Rennes] = Hepatobiliary and Digestive Surgery [Rennes], CHU Pontchaillou [Rennes], Service d'endocrinologie diabétologie et nutrition [Rennes], Université de Rennes (UR)-CHU Pontchaillou [Rennes]-Hôpital Anne-de-Bretagne, This study was funded by the Hed-O-Shift INRA Priority Action of the AlimH Division (Nutrition, Chemical Food Safety and Consumer Behaviour) and coordinated by David Val-Laillet. Damien Bergeat also received funding from the European Society for Clinical Nutrition and Metabolism to perform part of this project., and Bernard, Emilie
Subjects: Bariatric surgery, Gastric bypass, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Nutrition and Dietetics, Microbiota, Brain, Obesity, Critical Care and Intensive Care Medicine, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Functional MRI
Abstract: International audience; Background & aimsIn most cases, Roux-en-Y gastric bypass (RYGBP) is an efficient intervention to lose weight, change eating behavior and improve metabolic outcomes in obese patients. We hypothesized that weight loss induced by RYGBP in obese Yucatan minipigs would induce specific modifications of the gut–brain axis and neurocognitive responses to oral sucrose stimulation in relationship with food intake control.MethodsAn integrative study was performed after SHAM (n = 8) or RYGBP (n = 8) surgery to disentangle the physiological, metabolic and neurocognitive mechanisms of RYGBP. BOLD fMRI responses to sucrose stimulations at different concentrations, brain mRNA expression, cecal microbiota, and plasma metabolomics were explored 4 months after surgery and integrated with WGCNA analysis.ResultsWe showed that weight loss induced by RYGBP or SHAM modulated differently the frontostriatal responses to oral sucrose stimulation, suggesting a different hedonic treatment and inhibitory control related to palatable food after RYGBP. The expression of brain genes involved in the serotoninergic and cannabinoid systems were impacted by RYGBP. Cecal microbiota was deeply modified and many metabolite features were differentially increased in RYGBP. Data integration with WGCNA identified interactions between key drivers of OTUs and metabolites features linked to RYGBP.ConclusionThis longitudinal study in the obese minipig model illustrates with a systemic and integrative analysis the mid-term consequences of RYGBP on brain mRNA expression, cecal microbiota and plasma metabolites. We confirmed the impact of RYGBP on functional brain responses related to food reward, hedonic evaluation and inhibitory control, which are key factors for the success of anti-obesity therapy and weight loss maintenance.
Published: 2023

2. High Visceral Fat is Associated with a Worse Survival after Liver Resection for Intrahepatic Cholangiocarcinoma

Author: Laurence Lacaze, Damien Bergeat, Chloé Rousseau, Laurent Sulpice, David Val-Laillet, Ronan Thibault, Karim Boudjema, Service de Chirurgie Hépatobiliaire et Digestive [Rennes] = Hepatobiliary and Digestive Surgery [Rennes], CHU Pontchaillou [Rennes], Service d'endocrinologie diabétologie et nutrition [Rennes], Université de Rennes (UR)-CHU Pontchaillou [Rennes]-Hôpital Anne-de-Bretagne, Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Rennes (UR)
Subjects: fat-free mass, sarcopenia, Cancer Research, Nutrition and Dietetics, Oncology, cancer, Medicine (miscellaneous), malnutrition, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, adipose tissue
Abstract: International audience; The impact of body composition (BC) on the prognosis of resected intrahepatic cholangiocarcinoma (ICC) has been poorly studied. Aims: i) to evaluate the prevalence of low muscle mass (MM) in patients; ii) to assess the impact of BC on patient overall survival (OS) and disease-free survival (DFS), and iii) on the incidence of postoperative complications. All consecutive patients who underwent liver resection for ICC between 2004 and 2016 and who had preoperative CT scans were included. Ninety-three patients were included. Sixty percent (55/91) had low total MM. On multivariable analysis, high visceral fat (HR 2.48, CI95% [1.63; 3.77], p 1 (HR 3.15 [1.67; 5.93], p = 0.0004), involvement adjacent organ (HR 6.67 [1.88; 23.69], p = 0.003), and postoperative sepsis (HR 3.04 [1.54; 5.99], p = 0.0013) were independently associated with OS. High visceral fat (HR 2.10 [1.31; 3.38], p = 0.002], nodules >1 (HR 3.01, [1.49; 6.10], p = 0.002), postoperative sepsis (HR 5.16 [2.24; 11.89], p = 0.0001), ASA score (p = 0.02) and perineural invasion (HR 3.30 [1.62; 6.76], p = 0.001) were independently associated with lower DFS. Conclusion: 60% of ICC patients had low MM before surgery. High visceral fat, but not muscle mass, was an independent prognostic factor for poor OS and DFS in European patients with resected ICC.
Published: 2022

3. Access to device-aided therapies in advanced Parkinson’s disease: navigating clinician biases, patient preference, and prognostic uncertainty

Author: Auffret, Manon, Weiss, Daniel, Stocchi, Fabrizio, Vérin, Marc, Jost, Wolfgang H, Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR), Hertie Institute for Clinical Brain Research [Tubingen], University of Tübingen, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), and Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR)
Subjects: Parkinson’s disease, Personalised medicine, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Patient preference, Clinician bias, Device-aided therapies
Abstract: International audience; Device-aided therapies (DAT), which include deep brain stimulation and pump-based continuous dopaminergic stimulation with either levodopa or apomorphine, are among the major advances in the clinical management of Parkinson’s disease (PD). Although DAT are being increasingly offered earlier in the disease course, their classical indication remains advanced PD. Theoretically, every patient should be offered transition to DAT when faced with refractory motor and nonmotor fluctuations and functional decline. Worldwide clinical reality is far from these ideal, and, therefore, question the "real-world" equal opportunity of access to DAT for PD patients with advanced PD-even within a single health care system. Differences in access to care, referral pattern (timing and frequency), as well as physician biases (unconscious/implicit or conscious/explicit bias), and patients’ preferences or health-seeking behaviour are to be considered. Compared to DBS, little information is available concerning infusion therapies, as well as neurologists’ and patients’ attitudes towards them. This viewpoint aims to be thought-provoking and to assist clinicians in moving through the process of DAT selection, by including in their decision algorithm their own biases, patient perspective, ethical concerns as well as the current unknowns surrounding PD prognosis and DAT-related long-term side effects for a given patient.
Published: 2023

4. Antenatal ultrasound features of isolated recurrent copy number variation in 7q11.23 (Williams syndrome and 7q11.23 duplication syndrome)

Author: Cécile Courdier, John Boudjarane, Valérie Malan, Christine Muti, Brian Sperelakis‐Beedham, Sylvie Odent, Sylvie Jaillard, Chloé Quelin, Cédric Le Caignec, Olivier Patat, Charlotte Dubucs, Sophie Julia, Caroline Schluth‐Bolard, Carole Goumy, Sylvia Redon, Jean‐Baptiste Gaillard, Minh Tuan Huynh, Céline Dupont, Anne‐Claude Tabet, Guillaume Cogan, François Vialard, Rodolphe Dard, Guillaume Jedraszak, Florence Jobic, Mathilde Lefebvre, Geneviève Quenum, Saori Inai, Mélanie Rama, Fanny Sauvestre, Frédéric Coatleven, Julie Thomas, Caroline Rooryck, Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier de Versailles André Mignot (CHV), Service de génétique clinique [Rennes], Université de Rennes (UR)-CHU Pontchaillou [Rennes]-hôpital Sud, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de Cytogénétique et de Biologie Cellulaire, Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Service Génétique Médicale [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Unité différenciation épidermique et auto-immunité rhumatoïde (UDEAR), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Cytogénétique Constitutionnelle [Hospices civils de Lyon], Hospices Civils de Lyon (HCL), Laboratoire de Diagnostic Génétique [CHU Strasbourg], Université de Strasbourg (UNISTRA)-CHU Strasbourg, Service de Cytogénétique Médicale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Unité de Génétique Chromosomique [Montpellier], Département de Génétique Médicale, Maladies Rares et Médecine Personnalisée [Montpellier], Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre hospitalier universitaire de Nantes (CHU Nantes), AP-HP Hôpital universitaire Robert-Debré [Paris], CHI Poissy-Saint-Germain, Biologie de la Reproduction, Environnement, Epigénétique & Développement (BREED), École nationale vétérinaire - Alfort (ENVA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de génétique médicale et oncogénétique [CHU Amiens Picardie], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Libourne, Service de Génétique Médicale [Lille], Institut de génétique médicale-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre Hospitalier Universitaire de Bordeaux (CHU de Bordeaux), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) (U1211 INSERM/MRGM), Université de Bordeaux (UB)-Groupe hospitalier Pellegrin-Institut National de la Santé et de la Recherche Médicale (INSERM), and None
Subjects: [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Obstetrics and Gynecology, Genetics (clinical), [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Objective: We aimed to gather fetal cases carrying a 7q11.23 copy number variation (CNV) and collect precise clinical data to broaden knowledge of antenatal features in these syndromes.Methods: We retrospectively recruited unrelated cases with 7q11.23 deletion, known as Williams-Beuren syndrome (WBS), or 7q11.23 duplication who had prenatal ultrasound findings. We collected laboratory and clinical data, fetal ultrasound, cardiac ultrasound and fetal autopsy reports from 18 prenatal diagnostic centers throughout France.Results: 40 fetuses with WBS were collected and the most common features were intra-uterine growth retardation (IUGR) (70.0%, 28/40), cardiovascular defects (30.0%, 12/40), polyhydramnios (17.5%, 7/40) and protruding tongue (15.0%, 6/40). Fetal autopsy reports were available for 11 cases and were compared with ultrasound prenatal features. Four cases of fetuses with 7q11.23 microduplication were collected and prenatal ultrasound signs were variable and often isolated.Conclusion: This work strengthens the fact that 7q11.23 CNVs are associated with a broad spectrum of antenatal presentations. IUGR and cardiovascular defects were the most frequent ultrasound signs. By reporting the biggest series of antenatal WBS, we aim to better delineate distinctive signs in fetuses with 7q11.23 CNVs.
Published: 2023

5. Transanal irrigation is a better choice for bowel dysfunction in adults with spina bifida: a randomized controlled trial

Author: Charlène Brochard, Magali Jezequel, Anne Blanchard‐Dauphin, Jacques Kerdraon, Brigitte Perrouin‐Verbe, Anne‐Marie Leroi, Jean Michel Reymann, Benoît Peyronnet, Jeff Morçet, Laurent Siproudhis, CHU Pontchaillou [Rennes], The Enteric Nervous System in gut and brain disorders [U1235] (TENS), Institut National de la Santé et de la Recherche Médicale (INSERM)-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), CHU Lille, Centre Mutualiste de Kerpape, Ploemeur, Centre hospitalier universitaire de Nantes (CHU Nantes), Nutrition, Inflammation et axe Microbiote-Intestin-Cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de physiologie digestive, urinaire, respiratoire et de l'exercice [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'urologie [Rennes] = Urology [Rennes], Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Service des Maladies de l'Appareil Digestif [CHU Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and French Ministry of Health. Grant Number: 2013-A01520-45
Subjects: transanal irrigation, faecal incontinence, [SDV]Life Sciences [q-bio], Gastroenterology, bowel dysfunction, conservative treatment, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Spina bifida, randomised controlled trial
Abstract: International audience; Aim: To compare transanal irrigation with conservative bowel management for the treatment of bowel dysfunction in Spina bifida (SB) patients.Methods: Patients with SB and bowel dysfunction were randomly assigned to receive either transanal irrigation or conservative bowel management. The effectiveness of the treatment was defined as a decrease of 4 points in the neurogenic bowel dysfunction (NBD) score at week 10. Data on incontinence (Cleveland scores; Jorge-Wexner [JW]) and constipation (Knowles-Eccersley-Scott Symptom Constipation Score [KESS]) were recorded at 10 and 24 weeks after inclusion. Data were analysed on an intention-to-treat basis.Results: A total of 34 patients were randomised: 16 patients to conservative bowel management and 18 patients to transanal irrigation. A total of 19/31 (61%) patients improved at week 10, 13 (76%) in the transanal irrigation group versus six (43%) in the conservative group (p = 0.056). In the irrigation group, the decrease in NBD score was -6.9 (-9.9 to -4.02) versus -1.9 (-6.5 to -2.8) in the conservative group (p = 0.049 in univariate and p = 0.004 in multivariate analysis). The NBD, Cleveland (JW and KESS) and Rosenberg scores were significantly lower in the transanal irrigation group than in the conservative bowel management group at week 10.Conclusions: This prospective, randomised, controlled, multicentre study in adult patients with SB suggests that transanal irrigation may be more effective than conservative bowel management.
Published: 2023

6. Motor Symptom Asymmetry Predicts Cognitive and Neuropsychiatric Profile Following Deep Brain Stimulation of the Subthalamic Nucleus in Parkinson’s Disease: a 5-Year Longitudinal Study

Author: Philippe Voruz, Claire Haegelen, Frédéric Assal, Sophie Drapier, Dominique Drapier, Paul Sauleau, Marc Vérin, Julie A Péron, Hôpital Universitaire de Genève = University Hospitals of Geneva (HUG), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR), Centre Hospitalier Guillaume Régnier [Rennes], and The first author was funded by Swiss National Foundation grant no. 105314_182221 (PI: Prof. Julie Péron).
Subjects: Motor symptom asymmetry, Psychiatry and Mental health, Clinical Psychology, Cognition, Neuropsychology and Physiological Psychology, STN-DBS, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Cognitive vulnerability, General Medicine, Left hemisphere
Abstract: IntroductionRisk factors (e.g., motor symptom asymmetry) for short- and long-term cognitive and neuropsychiatric symptoms following deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson’s disease have yet to be fully identified. The objectives of the present study were to determine whether motor symptom asymmetry in Parkinson’s disease is one such risk factor and to identify predictors of subnormal cognitive decline.MethodsA total of 26 patients receiving STN-DBS (13 with left-sided motor symptoms and 13 with right-sided ones) underwent follow-up neuropsychological, depression and apathy assessments over a 5-year period. Nonparametric intergroup comparisons were performed on raw scores, as well as Cox regression analyses on standardized Mattis Dementia Rating Scale scores.ResultsCompared with patients who had predominantly left-sided symptoms, right-sided patients scored higher on both apathy (at 3 months and 36 months) and depressive symptoms (at 6 months and 12 months) and scored lower on global cognitive efficiency (at 36 months and 60 months). Survival analyses revealed that only right-sided patients had subnormal standardized dementia scores, which were negatively associated with the number of perseverations in the Wisconsin Card Scoring Test.ConclusionRight-sided motor symptoms are a risk factor for more severe short- and long-term cognitive and neuropsychiatric symptoms following STN-DBS, confirming literature findings on left hemispheric vulnerability.
Published: 2023

7. Clinical features and outcomes of COVID-19 patients hospitalized for psychiatric disorders: a French multi-centered prospective observational study

Author: Claire Jansen, Pierre Thomas, Djamila Bennabi, Dominique Drapier, Thomas Schwitzer, Delphine Capdevielle, Noe Teboul, Pascal Delamillieure, Emmanuelle Corruble, Christophe Schmitt, Daniela Dobre, Olivier C. Martin, Pierre Abdel Ahad, Antoine Pelissolo, Clément Vansteene, Benjamin Rolland, Marion Leboyer, Raymund Schwan, Fabienne Ligier, Wanda Yekhlef, Antoine Yrondi, Raphaël Gaillard, William Lecoeur, Radoine Haoui, Mathilde Roser, Vincent Laprevote, Catherine Massoubre, Sonia Dollfus, Fabien Joubert, Philip Gorwood, Neuropsychologie Cognitive et Physiopathologie de la Schizophrénie (NCPS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Civil de Strasbourg, Centre Psychothérapique de Nancy [Laxou] (CPN), Faculté de Médecine [Nancy], Université de Lorraine (UL), Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), GHU Paris Psychiatrie et Neurosciences, Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Département de psychiatrie adulte, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital La Colombière, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Imagerie et Stratégies Thérapeutiques de la Schizophrénie (ISTS), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier le Vinatier [Bron], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinique des maladies mentales et de l'encéphale (CMME - Service de psychiatrie), Hôpital Sainte-Anne-Université Paris Cité (UPCité), Service Psychiatrie et psychologie médicale [CHU Toulouse], Pôle Psychiatrie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Centre Hospitalier Gérard Marchant, Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre de Psychiatrie et Neurosciences (U894), Centre Psychothérapique de Nancy (CPN), Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, HAL UR1, Admin, 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), Service Universitaire d’Addictologie de Lyon [CH Le Vinatier, Bron] (Pôle MOPHA - SUAL), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), Etablissement Public de Santé Alsace Nord, Partenaires INRAE, Hôpital Sainte-Anne-Université de Paris (UP), Etablissement public de santé de Ville-Evrard (EPS), Service Psychiatrie et psychologie médicale [CHU Purpan], CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Population, [SDV.NEU.PC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Confusional state, Logistic regression, Lower risk, 03 medical and health sciences, 0302 clinical medicine, Organic mental disorders, Intensive care, medicine, Psychiatry, Prospective cohort study, education, Applied Psychology, Univariate analysis, education.field_of_study, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, business.industry, Medical record, COVID-19, Odds ratio, medicine.disease, Mental health, Confidence interval, 030227 psychiatry, 3. Good health, [SDV] Life Sciences [q-bio], Psychiatry and Mental health, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Original Article, Observational study, business, 030217 neurology & neurosurgery
Abstract: Background: At the beginning of COVID-19 pandemic, specific COVID/PSY wards were created in France to provide care for inpatients with COVID-19 and psychiatric disorders. In this multi-center prospective study, we set out to assess the clinical features and risk factors of somatic aggravation in patients hospitalized in COVID/PSY wards. Methods: Data were collected between 28 February and 30 May, 2020. We collected demographic data, psychiatric diagnoses, medical data and COVID-19-related clinical data. Somatic aggravation was estimated by the number of patients transferred to intensive care or medicine units, the number of deaths and the number of patients presenting a confusional state. A multivariate logistic model was used to assess the risk factors of confusional state and transfer to intensive care or medicine units. The risk of death was analysed by the univariate predictors of this outcome. Outcomes: 350 patients were included in the study. The number of inclusions peaked one week after that of the general population and declined more slowly. Overall, 24 (7%) were transferred to medicine units, 7 (2%) died and 51 (15%) patients presented a confusional state. Severe respiratory symptoms predicted the transfer to a medicine unit (OR 17.1; CI 4.9-59.3). Older age, an organic mental disorder, a confusional state, and severe respiratory symptoms predicted mortality in univariate analysis. Age > 55 (OR 4.9; CI 2.1-11.4), an affective disorder (OR 4.1; CI 1.6-10.9), and severe respiratory symptoms (OR 4.6; CI 2.2-9.7) predicted a higher risk, while smoking (OR 0.3; CI 0.1-0.9) predicted a lower risk of a confusional state. Interpretation: COVID-19 patients with severe psychiatric disorders have multiple somatic comorbidities and a high risk of confusion. COVID/PSY wards may play a role in reducing the mortality of COVID-19 in patients with psychiatric disorders. Funding Statement: There was no funding source for this study. Declaration of Interests: There are no conflicts of interest to be declared. Ethics Approval Statement: This observational study was conducted according to the principles of the Declaration of Helsinki. In accordance with French bioethics laws, it was classified as a non- interventional study, since it concerned anonymized clinical data that are routinely compiled in medical records. Compliance with French regulations on personal data collection was supervised by the personal data referent of the Centre Psychotherapique de Nancy. Patients, and their legal guardian when appropriate, were informed in writing, in agreement with national regulations for observational studies.
Published: 2023

8. ESPEN guideline on hospital nutrition

Author: Stephan C. Bischoff, Elisabet Rothenberg, M. Vaillant, Ulla Siljamäki-Ojansuu, Elina Ioannou, Karen Ottens-Oussoren, Osman Abbasoglu, Laila Meija, Ronan Thibault, Diana Rubin, Claude Pichard, CHU Pontchaillou [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-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), Service d'endocrinologie diabétologie et nutrition [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-Hôpital Anne-de-Bretagne, Faculty of Medicine [Hacettepe University], Hacettepe University = Hacettepe Üniversitesi, Limassol General Hospital, Riga Stradins University (RSU), VU University Medical Center [Amsterdam], Hôpitaux Universitaires de Genève (HUG), Kristianstad University College - HKR (SWEDEN), Tampere University Hospital, CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, University of Hohenheim, This guideline was solely financed by ESPEN, the European Society for Clinical Nutrition and Metabolism., Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Université de Rennes (UR)-CHU Pontchaillou [Rennes]-Hôpital Anne-de-Bretagne
Subjects: medicine.medical_specialty, Monitoring, [SDV]Life Sciences [q-bio], Acute care, Clinical nutrition, Critical Care and Intensive Care Medicine, 03 medical and health sciences, Patient safety, 0302 clinical medicine, Intolerances, Food intake, medicine, 030212 general & internal medicine, Medical prescription, ddc:616, 2. Zero hunger, Nutrition and Dietetics, business.industry, Malnutrition, Guideline, Diets, medicine.disease, Obesity, 3. Good health, Family medicine, 030211 gastroenterology & hepatology, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: International audience; In hospitals through Europe and worldwide, the practices regarding hospital diets are very heterogeneous. Hospital diets are rarely prescribed by physicians, and sometimes the choices of diets are based on arbitrary reasons. Often prescriptions are made independently from the evaluation of nutritional status, and without taking into account the nutritional status. Therapeutic diets (low salt, gluten-free, texture and consistency modified, …) are associated with decreased energy delivery (i.e. underfeeding) and increased risk of malnutrition. The European Society for Clinical Nutrition and Metabolism (ESPEN) proposes here evidence-based recommendations regarding the organization of food catering, the prescriptions and indications of diets, as well as monitoring of food intake at hospital, rehabilitation center, and nursing home, all of these by taking into account the patient perspectives. We propose a systematic approach to adapt the hospital food to the nutritional status and potential food allergy or intolerances. Particular conditions such as patients with dysphagia, older patients, gastrointestinal diseases, abdominal surgery, diabetes, and obesity, are discussed to guide the practitioner toward the best evidence based therapy. The terminology of the different useful diets is defined. The general objectives are to increase the awareness of physicians, dietitians, nurses, kitchen managers, and stakeholders towards the pivotal role of hospital food in hospital care, to contribute to patient safety within nutritional care, to improve coverage of nutritional needs by hospital food, and reduce the risk of malnutrition and its related complications.
Published: 2021

9. Psychotropics and COVID-19: An analysis of safety and prophylaxis

Author: Bastien Langrée, Eric Fakra, C. Straczek, C. Gitahy Falcao Faria, Marion Leboyer, S. Dizet, P.-M. Llorca, Raphaël Gaillard, Dominique Drapier, Hervé Javelot, M. Masson, Sébastien Weibel, Luisa Weiner, G Meyer, Philippe Fossati, Emmanuel Haffen, Antoine Yrondi, C. Hingray, Laboratoire de pharmacologie et de toxicologie neurocardiovasculaire (LPTNC), Université de Strasbourg (UNISTRA), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Strasbourg, Universidade Federal do Rio de Janeiro (UFRJ), Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], CHU Pontchaillou [Rennes]-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université européenne de Bretagne - European University of Brittany (UEB)-Institut des Neurosciences Cliniques de Rennes (INCR), Centre Hospitalier Guillaume Régnier [Rennes], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Les Hôpitaux Universitaires de Strasbourg (HUS), Centre Hospitalier Chalon-sur-Saône William Morey, GHU Paris Psychiatrie et Neurosciences, Conseil national des universités (CNU), CHU Clermont-Ferrand, Université Clermont Auvergne (UCA), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Université Bourgogne Franche-Comté [COMUE] (UBFC), Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Jonchère, Laurent, Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], Context (language use), 03 medical and health sciences, 0302 clinical medicine, Arts and Humanities (miscellaneous), Pandemic, medicine, Humans, Bipolar disorder, Psychiatry, Pandemics, Depression (differential diagnoses), Review of the Literature, Psychotropic Drugs, Prophylaxis, SARS-CoV-2, business.industry, Psychotropics, COVID-19, Guideline, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, medicine.disease, Mental health, COVID-19 Drug Treatment, 030227 psychiatry, 3. Good health, [SDV] Life Sciences [q-bio], [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Psychotropes, Psychiatry and Mental health, Sécurité clinique, Schizophrenia, Prophylaxie, Safety, business, 030217 neurology & neurosurgery, Anxiety disorder
Abstract: International audience; The use of psychotropics during the COVID-19 pandemic has raised two questions, in order of importance: first, what changes should be made to pharmacological treatments prescribed to mental health patients? Secondly, are there any positive side effects of these substances against SARS-CoV-2? Our aim was to analyze usage safety of psychotropics during COVID-19; therefore, herein, we have studied: (i) the risk of symptomatic complications of COVID-19 associated with the use of these drugs, notably central nervous system activity depression, QTc interval enlargement and infectious and thromboembolic complications; (ii) the risk of mistaking the iatrogenic impact of psychotropics with COVID-19 symptoms, causing diagnostic error. Moreover, we provided a summary of the different information available today for these risks, categorized by mental health disorder, for the following: schizophrenia, bipolar disorder, anxiety disorder, ADHD, sleep disorders and suicidal risk. The matter of psychoactive substance use during the pandemic is also analyzed in this paper, and guideline websites and publications for psychotropic treatments in the context of COVID-19 are referenced during the text, so that changes on those guidelines and eventual interaction between psychotropics and COVID-19 treatment medication can be reported and studied. Finally, we also provide a literature review of the latest known antiviral properties of psychotropics against SARS-CoV-2 as complementary information.
Published: 2021

10. An electroencephalography connectome predictive model of major depressive disorder severity

Author: Kabbara, Aya, Robert, Gabriel, Khalil, Mohamad, Verin, Marc, Benquet, Pascal, Hassan, Mahmoud, Lebanese Association for Scientific Research [Tripoli] (LASeR), MINDig, Centre Hospitalier Guillaume Régnier [Rennes], Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Comportement et noyaux gris centraux - EA 4712, Université de Rennes (UR)-Institut des Neurosciences Cliniques de Rennes (INCR), emlyon business school (EM), Lebanese University [Beirut] (LU), Ecole Doctorale des Sciences et de la Technologie (EDST), Azm Center for research in biotechnology and its applications [TRIPOLI], Université Libanaise, CHU Pontchaillou [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Reykjavík University, robert, gabriel, Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), This work was financed by the Rennes University, the Institute of Clinical Neuroscience of Rennes (Projects named EEGCog and EEGNET3). This work was also financed by the AZM and SAADE Association, Tripoli, Lebanon and by the National Council for Scientific Research (CNRS) in Lebanon. Authors would like to thank Campus France, Programme Hubert Curien CEDRE (PROJET N° 42257YA) and the Lebanese Association for Scientific Research (LASER) for their support, HAL UR1, Admin, Université de Rennes (UR)-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR), and Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR)
Subjects: [SDV.IB] Life Sciences [q-bio]/Bioengineering, Depressive Disorder, Major, Multidisciplinary, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, [SDV]Life Sciences [q-bio], [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, [SDV.NEU.PC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Brain, Electroencephalography, [STAT] Statistics [stat], Machine Learning, [STAT]Statistics [stat], [SDV] Life Sciences [q-bio], FOS: Biological sciences, Quantitative Biology - Neurons and Cognition, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Connectome, Humans, Neurons and Cognition (q-bio.NC), [SDV.IB]Life Sciences [q-bio]/Bioengineering, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, [SPI.SIGNAL] Engineering Sciences [physics]/Signal and Image processing
Abstract: Emerging evidence showed that major depressive disorder (MDD) is associated with disruptions of brain structural and functional networks, rather than impairment of isolated brain region. Thus, connectome-based models capable of predicting the depression severity at the individual level can be clinically useful. Here, we applied a machine-learning approach to predict the severity of depression using resting-state networks derived from source-reconstructed Electroencephalography (EEG) signals. Using regression models and three independent EEG datasets (N = 328), we tested whether resting state functional connectivity could predict individual depression score. On the first dataset, results showed that individuals scores could be reasonably predicted (r = 0.6, p = 4 × 10–18) using intrinsic functional connectivity in the EEG alpha band (8–13 Hz). In particular, the brain regions which contributed the most to the predictive network belong to the default mode network. We further tested the predictive potential of the established model by conducting two external validations on (N1 = 53, N2 = 154). Results showed statistically significant correlations between the predicted and the measured depression scale scores (r1 = 0.52, r2 = 0.44, p
Published: 2022

11. Oral Health Disorders in Parkinson’s Disease: More than Meets the Eye

Author: Marc Vérin, Manon Auffret, Vincent Meuric, Emile Boyer, Martine Bonnaure-Mallet, CHU Pontchaillou [Rennes], Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], CHU Pontchaillou [Rennes]-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université européenne de Bretagne - European University of Brittany (UEB)-Institut des Neurosciences Cliniques de Rennes (INCR), Institut des Neurosciences Cliniques de Rennes (INCR), Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-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), This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR), Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: medicine.medical_specialty, Parkinson's disease, Isolation (health care), [SDV]Life Sciences [q-bio], Disease, Review, Anxiety, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Quality of life, Tremor, medicine, microbiota, Humans, Intensive care medicine, Depression (differential diagnoses), dentistry, business.industry, Parkinson Disease, 030206 dentistry, medicine.disease, 3. Good health, Malnutrition, Dyskinesia, interdisciplinary research, Parkinson’s disease, Quality of Life, oral health, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery, stomatognathic diseases
Abstract: International audience; Despite clinical evidence of poor oral health and hygiene in Parkinson’s disease (PD) patients, the mouth is often overlooked by both patients and the medical community, who generally focus on motor or psychiatric disorders considered more burdensome. Yet, oral health is in a two-way relationship with overall health-a weakened status triggering a decline in the quality of life. Here, we aim at giving a comprehensive overview of oral health disorders in PD, while identifying their etiologies and consequences. The physical (abnormal posture, muscle tone, tremor, and dyskinesia), behavioral (cognitive and neuropsychiatric disorders), and iatrogenic patterns associated with PD have an overall detrimental effect on patients’ oral health, putting them at risk for other disorders (infections, aspiration, pain, malnutrition), reducing their quality of life and increasing their isolation (anxiety, depression, communication issues). Interdisciplinary cooperation for prevention, management and follow-up strategies need to be implemented at an early stage to maintain and improve patients’ overall comfort and condition. Recommendations for practice, including (non-)pharmacological management strategies are discussed, with an emphasis on the neurologists’ role. Of interest, the oral cavity may become a valuable tool for diagnosis and prognosis in the near future (biomarkers). This overlooked but critical issue requires further attention and interdisciplinary research.
Published: 2021

12. Unpredicted failure of deep brain stimulation by the impedance measures in a child with severe PANK2- gene related generalized dystonia

Author: Matthieu Villessot, Diane Demailly, Emilie Chan-Seng, Gaëtan Poulen, Sophie Huby, Thomas Roujeau, Morgan Dornadic, Marc Vérin, Audrey Riou, Philippe Coubes, Laura Cif, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Pontchaillou [Rennes], Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], and Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR)
Subjects: DBS failure, Impedance measures, General Neuroscience, Deep Brain Stimulation, [SDV]Life Sciences [q-bio], Biophysics, DYT-PANK2, Globus Pallidus, Dystonia, Treatment Outcome, Dystonic Disorders, Electric Impedance, Humans, Neurology (clinical), Child
Abstract: International audience
Published: 2022

13. In silico model reveals the key role of GABA in KCNT1 ‐epilepsy in infancy with migrating focal seizures

Author: Paul Sauleau, Rima Nabbout, Julien Modolo, Pascal Benquet, Maxime Yochum, Mathieu Kuchenbuch, Fabrice Wendling, Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), CHU Pontchaillou [Rennes], Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), Fondation Bettencourt Schueller, ANR‐10‐IAHU‐01), Agence Nationale de la Recherche, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR), and ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010)
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], In silico, Macroscopic model, Nerve Tissue Proteins, Potassium Channels, Sodium-Activated, Biology, Electroencephalography, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, developmental epileptic encephalopathy, Seizures, pathophysiological mechanisms, medicine, Humans, Computer Simulation, Ictal, GABAergic Neurons, medicine.diagnostic_test, depolarizing GABA, Infant, Depolarization, medicine.disease, Phenotype, 030104 developmental biology, Neurology, Gain of Function Mutation, computational models, malignant migrating partial seizure in infancy, GABAergic, Neurology (clinical), Neuroscience, 030217 neurology & neurosurgery
Abstract: International audience; OBJECTIVE: This study was undertaken to investigate how gain of function (GOF) of slack channel due to a KCNT1 pathogenic variant induces abnormal neuronal cortical network activity and generates specific electroencephalographic (EEG) patterns of epilepsy in infancy with migrating focal seizures. METHODS: We used detailed microscopic computational models of neurons to explore the impact of GOF of slack channel (explicitly coded) on each subtype of neurons and on a cortical micronetwork. Then, we adapted a thalamocortical macroscopic model considering results obtained in detailed models and immature properties related to epileptic brain in infancy. Finally, we compared simulated EEGs resulting from the macroscopic model with interictal and ictal patterns of affected individuals using our previously reported EEG markers. RESULTS: The pathogenic variants of KCNT1 strongly decreased the firing rate properties of γ-aminobutyric acidergic (GABAergic) interneurons and, to a lesser extent, those of pyramidal cells. This change led to hyperexcitability with increased synchronization in a cortical micronetwork. At the macroscopic scale, introducing slack GOF effect resulted in epilepsy of infancy with migrating focal seizures (EIMFS) EEG interictal patterns. Increased excitation-to-inhibition ratio triggered seizure, but we had to add dynamic depolarizing GABA between somatostatin-positive interneurons and pyramidal cells to obtain migrating seizure. The simulated migrating seizures were close to EIMFS seizures, with similar values regarding the delay between the different ictal activities (one of the specific EEG markers of migrating focal seizures due to KCNT1 pathogenic variants). SIGNIFICANCE: This study illustrates the interest of biomathematical models to explore pathophysiological mechanisms bridging the gap between the functional effect of gene pathogenic variants and specific EEG phenotype. Such models can be complementary to in vitro cellular and animal models. This multiscale approach provides an in silico framework that can be further used to identify candidate innovative therapies.
Published: 2021

14. Coprologie parasitaire : conduite de l’examen et pièges diagnostiques

Author: Brice Autier, Dominique Chabasse, Claude Guiguen, Jean-Pierre Gangneux, Service de Parasitologie-Mycologie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], and Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: [SDV]Life Sciences [q-bio], Biochemistry (medical), 030204 cardiovascular system & hematology, 3. Good health, Analytical Chemistry, 03 medical and health sciences, Medical Laboratory Technology, parasite intestinal, 0302 clinical medicine, protozoaire, 030220 oncology & carcinogenesis, helminthe, faux parasite, selles
Abstract: International audience; L’examen parasitologique des selles consiste, le plus souvent, à examiner celles-ci macro- et microscopiquement à la recherche de parasites intestinaux : formes végétatives et kystiques des protozoaires ; œufs, larves et adultes d’helminthes. Le principe du diagnostic fait appel à des techniques analytiques à la portée de tous les laboratoires de biologie médicale. Les renseignements épidémiologiques, cliniques et biologiques doivent être correctement documentés pour une démarche diagnostique optimale. L’examen parasitologique des selles doit être réalisé par un personnel averti, formé à la diagnose des différentes espèces de parasites pouvant infecter l’homme mais il doit également savoir reconnaître les éléments non pathogènes et les faux-parasites.
Published: 2021

15. Crossed functional specialization between the basal ganglia and cerebellum during vocal emotion decoding: Insights from stroke and Parkinson’s disease

Author: Marine Thomasson, Damien Benis, Philippe Voruz, Arnaud Saj, Marc Vérin, Frédéric Assal, Didier Grandjean, Julie Péron, Université de Genève = University of Geneva (UNIGE), Université de Montréal (UdeM), Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR), CHU Pontchaillou [Rennes], and Open access funding provided by University of Geneva The project was funded by Swiss National Foundation grant no. 105314_182221 (PI: Dr Julie Péron).
Subjects: Stroke, Behavioral Neuroscience, Cognitive Neuroscience, Cerebellum, [SDV]Life Sciences [q-bio], Emotions, Basal ganglia, Parkinson’s disease, Humans, Parkinson Disease, Vocal emotion
Abstract: There is growing evidence that both the basal ganglia and the cerebellum play functional roles in emotion processing, either directly or indirectly, through their connections with cortical and subcortical structures. However, the lateralization of this complex processing in emotion recognition remains unclear. To address this issue, we investigated emotional prosody recognition in individuals with Parkinson’s disease (model of basal ganglia dysfunction) or cerebellar stroke patients, as well as in matched healthy controls (n = 24 in each group). We analysed performances according to the lateralization of the predominant brain degeneration/lesion. Results showed that a right (basal ganglia and cerebellar) hemispheric dysfunction was likely to induce greater deficits than a left one. Moreover, deficits following left hemispheric dysfunction were only observed in cerebellar stroke patients, and these deficits resembled those observed after degeneration of the right basal ganglia. Additional analyses taking disease duration / time since stroke into consideration revealed a worsening of performances in patients with predominantly right-sided lesions over time. These results point to the differential, but complementary, involvement of the cerebellum and basal ganglia in emotional prosody decoding, with a probable hemispheric specialization according to the level of cognitive integration.
Published: 2022

16. A cell-based system combined with flow cytometry to evaluate antibody responses against SARS-CoV-2 transmembrane proteins in patients with COVID-19

Author: Sophie Martin, Gwénaële Jégou, Aurore Nicolas, Matthieu Le Gallo, Éric Chevet, Florence Godey, Tony Avril, Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), CHU Pontchaillou [Rennes], Centre de Ressources Biologiques Santé (CRB Santé), Université de Rennes (UR)-CHU Pontchaillou [Rennes]-CRLCC Eugène Marquis (CRLCC), This work was funded by grants from INSERM, Institut National du Cancer (INCa PLBIO), Fondation pour la Recherche Médicale (FRM, DEQ20180339169) to E.C. and from la Ligue contre le cancer (comité 35, 56, et 85) to T.A., and Jonchère, Laurent
Subjects: Microbiology, General Immunology and Microbiology, Health Sciences, SARS-CoV-2, General Neuroscience, COVID-19, Membrane Proteins, [SDV.CAN]Life Sciences [q-bio]/Cancer, Antibody, Flow Cytometry, Cell Biology, General Biochemistry, Genetics and Molecular Biology, HEK293 Cells, [SDV.CAN] Life Sciences [q-bio]/Cancer, Antibody Formation, Spike Glycoprotein, Coronavirus, Humans, Flow Cytometry/Mass Cytometry, Cell-based Assays, Molecular Biology
Abstract: International audience; This protocol describes a flow cytometry approach to evaluate antibody responses against SARS-CoV-2 transmembrane proteins in COVID-19-positive patient sera samples without the need of specific laboratory facilities for viral infection. We developed a human-cell-based system using spike-expressing HEK293T cells that mimics membrane insertion and N-glycosylation of viral integral membrane proteins in host cells. This assay represents a powerful tool to test antibody responses against SARS-CoV-2 variants and vaccine effectiveness. For complete details on the use and execution of this protocol, please refer to Martin et al. (2021).
Published: 2022

17. La néphropathie induite par le lysozyme : une cause rare d’insuffisance rénale dans la leucémie myélomonocytaire chronique

Author: Cécile Le Naourès, Gwladys Robinet-Zimmermann, Nathalie Rioux-Leclercq, Thierry Frouget, Service d'anatomie et cytologie pathologiques [Rennes] = Anatomy and Cytopathology [Rennes], CHU Pontchaillou [Rennes], Service de néphrologie [Rennes], CHU Pontchaillou [Rennes]-Hôpital Pontchaillou-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
Subjects: 0301 basic medicine, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, business.industry, [SDV]Life Sciences [q-bio], 030220 oncology & carcinogenesis, Medicine, business, Molecular biology, 3. Good health, Pathology and Forensic Medicine
Abstract: Resume Introduction La nephropathie induite par le lysozyme est une complication rare et peu connue de la leucemie myelomonocytaire chronique. Elle est caracterisee par une toxicite vis-a-vis de l’epithelium tubulaire proximal du lysozyme produit en exces par les cellules tumorales. Nous presentons ici le cas d’une nephropathie au lysozyme dans un contexte de leucemie myelomonocytaire chronique. Observation Il s’agissait d’une patiente de 82 ans presentant une insuffisance renale aigue associee a des diarrhees et vomissements. Ses antecedents etaient marques par une leucemie myelomonocytaire chronique en surveillance simple et une hypertension arterielle. Malgre la rehydratation, la fonction renale continuait a se degrader. La biopsie renale retrouvait une nephropathie tubulo-interstitielle induite par le lysozyme avec une vacuolisation de l’epithelium tubulaire par des gouttelettes eosinophiles marquees par l’anticorps anti-lysozyme, sans localisation renale tumorale. Conclusion La nephropathie induite par le lysozyme est une pathologie rare dont le diagnostic peut etre suspecte biologiquement et confirme par une etude histologique. Les autres causes d’insuffisance renale dans un contexte de leucemie myelomonocytaire chronique doivent etre eliminees en premier lieu. Le traitement est symptomatique et s’accompagne du traitement de la pathologie hematologique sous-jacente.
Published: 2020

18. French Validation of the Alcohol Urge Questionnaire: Psychometric Properties and Relationship with Alcohol Dependence and Drinking Behavior

Author: Aymery Constant, Florian Naudet, Marc Vérin, Marlene Sanz, Romain Moirand, Manon Auffret, Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), École des Hautes Études en Santé Publique [EHESP] (EHESP), Département des sciences humaines et sociales (SHS), CHU Pontchaillou [Rennes], Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR), Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR), 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), Institut des Neurosciences Cliniques de Rennes (INCR), EHESP, SCD, and Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR)
Subjects: Male, French, Psychometrics, Health Status, medicine.medical_treatment, Craving, Severity of Illness Index, [SHS]Humanities and Social Sciences, 0302 clinical medicine, Recurrence, Surveys and Questionnaires, media_common, validation, Alcohol detoxification, General Medicine, Middle Aged, Alcoholism, Female, [SHS] Humanities and Social Sciences, France, medicine.symptom, Alcohol, Addictive behavior, Alcohol Dependence, Clinical psychology, Adult, Alcohol Drinking, Visual analogue scale, media_common.quotation_subject, Drinking Behavior, Alcohol Urge Questionnaire, Unit of alcohol, 03 medical and health sciences, medicine, Humans, Translations, Questionnaire, business.industry, Addiction, Alcohol dependence, Reproducibility of Results, medicine.disease, 030227 psychiatry, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Stress, Psychological, 030217 neurology & neurosurgery
Abstract: Aim To validate a French translation of the Alcohol Urge Questionnaire (AUQ) that measures craving in patients with alcohol dependence. Method All patients aged > 18 years who were hospitalized for alcohol detoxification from February to May 2019 in the alcohol unit of the Rennes university hospital were eligible. A back-translated version of the AUQ was completed at admission. Patients were interviewed at the end of the 7-day detoxification program by a trained addiction psychiatrist (MS), using tablet computed-based questionnaires assessing state craving (visual analog scale), alcohol dependence severity, drinking behavior, psychological distress and physical/mental health. The same investigator assessed relapse 1 month after discharge. Results A total of 80 inpatients were recruited and completed questionnaires. The single factor structure of the French version of the AUQ was similar to the original questionnaire, and was supported by strong internal reliability and item-scale validity. The AUQ score correlated highly acute craving measure, but moderately scales assessing the severity of alcohol dependence, drinking behavior and mental health. Relapse 1 month after discharge was significantly related to AUQ score assessed either at baseline, or with better estimate at the end of the 7-day detoxification period. Conclusion The French version of the AUQ provides a reliable measure of phasic craving, which is best described as a context-dependent single-factor variable, related to but distinct from tonic craving, dependence severity and drinking behavior. The ease of administration makes the AUQ a useful tool for French-speaking patients with alcohol dependence.
Published: 2020

19. Selective SIRPα blockade reverses tumor T cell exclusion and overcomes cancer immunotherapy resistance

Author: Riad Abes, Kevin Biteau, Alexandre Glémain, Christophe Blanquart, Dominique Costantini, Catherine Ruiz, David Laplaud, Hélène Aublé, Stéphanie Le Bas-Bernardet, E. Sergio Trombetta, Véronique Catros, Gilles Blancho, Isabelle Archambeaud, Sylvie Métairie, Isabelle Girault, Emmanuelle Wilhelm, Masayuki Miyasaka, Jean-François Mosnier, Vanessa Gauttier, Sabrina Pengam, Charlène Trilleaud, Alexandra Garcia, Pierre-Antoine Gouraud, Pierre Duplouye, Bernard Martinet, Géraldine Teppaz, Georgia Porto, Fabienne Haspot, Sarah Bruneau, Aurore Morello, Justine Durand, Caroline Mary, Richard Danger, Sophie Conchon, Nathalie Labarrière, Kerry L. M. Ralph, Virginie Thepenier, Nicolas Vince, Nicolas Poirier, Bernard Vanhove, Virginie Vignard, Mélanie Néel, Safa Dehmani, OSE Immunotherapeutics [Nantes, France], Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre hospitalier universitaire de Nantes (CHU Nantes), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Boehringer Ingelheim Pharma GmbH & Co. KG, Osaka University, Anti-Tumor Immunosurveillance and Immunotherapy (CRCINA-ÉQUIPE 3), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Université de Nantes (UN), Immunogenic Cell Death and Mesothelioma Therapy (CRCINA-ÉQUIPE 4), Nutrition, Métabolismes et Cancer (NuMeCan), 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Pontchaillou [Rennes], Centre de Ressources Biologiques Santé (CRB Santé), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-CRLCC Eugène Marquis (CRLCC), Institut des maladies de l'appareil digestif [Nantes] (IMAD), BPI EFFI-CLIN PSPC grant,INCA MDSCAN PRT-K15-136, the French Public Bank of Investment and French Institut National du Cancer, Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Rennes (UR)-CHU Pontchaillou [Rennes]-CRLCC Eugène Marquis (CRLCC), and Jonchère, Laurent
Subjects: 0301 basic medicine, T-Lymphocytes, [SDV]Life Sciences [q-bio], T cell, medicine.medical_treatment, Immunology, T cells, Cancer immunotherapy, Therapeutics, Mice, 03 medical and health sciences, 0302 clinical medicine, medicine, Animals, Receptors, Immunologic, Mice, Inbred BALB C, Tumor microenvironment, Chemistry, Macrophages, CD47, Mammary Neoplasms, Experimental, General Medicine, Immune checkpoint, Neoplasm Proteins, 3. Good health, Blockade, [SDV] Life Sciences [q-bio], 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Chemokine secretion, Cancer research, Female, Immunotherapy, Immunologic Memory, Memory T cell, Research Article
Abstract: International audience; T cell exclusion causes resistance to cancer immunotherapies via immune checkpoint blockade (ICB). Myeloid cells contribute to resistance by expressing signal regulatory protein-α (SIRPα), an inhibitory membrane receptor that interacts with ubiquitous receptor CD47 to control macrophage phagocytosis in the tumor microenvironment. Although CD47/SIRPα-targeting drugs have been assessed in preclinical models, the therapeutic benefit of selectively blocking SIRPα, and not SIRPγ/CD47, in humans remains unknown. We report a potent synergy between selective SIRPα blockade and ICB in increasing memory T cell responses and reverting exclusion in syngeneic and orthotopic tumor models. Selective SIRPα blockade stimulated tumor nest T cell recruitment by restoring murine and human macrophage chemokine secretion and increased anti-tumor T cell responses by promoting tumor-antigen crosspresentation by dendritic cells. However, nonselective SIRPα/SIRPγ blockade targeting CD47 impaired human T cell activation, proliferation, and endothelial transmigration. Selective SIRPα inhibition opens an attractive avenue to overcoming ICB resistance in patients with elevated myeloid cell infiltration in solid tumors.
Published: 2020

20. Sequential allogeneic hematopoietic stem cell transplantation for active refractory/relapsed myeloid malignancies: results of a reduced-intensity conditioning preceded by clofarabine and cytosine arabinoside, a retrospective study on behalf of the SFGM-TC

Author: Natacha Maillard, Sylvain Chantepie, Tony Marchand, Myriam Labopin, Régis Peffault de Latour, Ibrahim Yakoub-Agha, Karin Bilger, Didier Blaise, Pascal Turlure, Marie C. Béné, Société Francophone de Greffe de Moelle et de Thérapie Cellulaire, Mohamad Mohty, Marie-Thérèse Rubio, Patrice Chevallier, Stéphanie Nguyen, Edouard Forcade, Patrice Ceballos, Anne Huynh, Amandine Charbonnier, Ambroise Marçais, Amandine Le Bourgeois, Thierry Guillaume, Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Pathologies biliaires, fibrose et cancer du foie [CRSA], 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hémato-oncologie [CHU Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Pitié-Salpêtrière [AP-HP], Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Bordeaux [Bordeaux], Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service d'Hématologie, Immunologie et de Thérapie Cellulaire (HITC), Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Département d'Oncologie et Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Service d'hématologie et oncologie médicale, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM), CHU Amiens-Picardie, CHU Limoges, Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Pathologies biliaires, fibrose et cancer du foie [CHU Saint-Antoine], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Toulouse [Toulouse], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Hôpital Lapeyronie-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Oncology, medicine.medical_specialty, Transplantation Conditioning, Adolescent, Cyclophosphamide, medicine.medical_treatment, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematopoietic stem cell transplantation, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Clofarabine, education, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Chemotherapy, education.field_of_study, business.industry, Cytarabine, Hematopoietic Stem Cell Transplantation, Hematology, General Medicine, Middle Aged, Allografts, 3. Good health, Survival Rate, Transplantation, Leukemia, Myeloid, Acute, Regimen, Myelodysplastic Syndromes, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Busulfan, 030215 immunology, medicine.drug
Abstract: Allogeneic stem cell transplantation (allo-SCT) represents the most beneficial treatment for patients with active relapsed/refractory (R/R) hematologic malignancies. Recently, sequential regimens combining debulking chemotherapy followed by reduced-intensity conditioning (RIC) have shown encouraging results for these patients. In this retrospective study, we report the extended results of a sequential regimen of clofarabine, cytosine arabinoside, and RIC in 131 adults with active R/R myeloid disease at transplant. Conditioning consisted of clofarabine (30 mg/m2/day) and cytosine arabinoside (1 g/m2/day) for 5 days, followed, after a rest of 3 days, by an RIC combining cyclophosphamide (60 mg/kg) for 1 day, iv busulfan (3.2 mg/kg/day) for 2 days, and anti-thymocyte globulin (2.5 mg/kg/day) for 2 days. Between 2007 and 2016, 131 patients (males n = 75, median age: 52.6 years) were identified from the SFGM-TC registry. There were 111 acute myeloid leukemia (AML) patients and 20 cases with myelodysplastic or myeloproliferative syndrome. Status at transplant was known for all but 4 patients and was primary refractory (n = 81) and 1st or 2nd relapse (n = 46). All patients received allo-SCT from a matched donor (sibling n = 64, unrelated n = 67). Engraftment was observed in 105/122 (86%) evaluable cases and 63% of the patients achieved complete remission (CR) after transplant. The 1-year overall survival, disease-free survival, relapse incidence, non-relapse mortality, and graft-versus-host disease-free/relapse-free survival were 39.2%, 28.1%, 41.0%, 30.8%, and 22.2%, respectively. This study confirms that this sequential clofarabine-based regimen provides a high CR rate in this critical population, although relapse remains a matter of concern.
Published: 2020

21. Affirmation de l’obstruction sous-vésicale avant chirurgie

Author: Imad Bentellis, J. Kerdraon, M. El-Akri, A. Manunta, C. Voiry, Juliette Hascoet, B. Peyronnet, Q. Alimi, Service d'urologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'urologie [Rennes] = Urology [Rennes], Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Médecine physique et de réadaptation [Rennes] (MPR), and CHU Pontchaillou [Rennes]
Subjects: 03 medical and health sciences, 030219 obstetrics & reproductive medicine, 0302 clinical medicine, [SDV]Life Sciences [q-bio], Urology, 030232 urology & nephrology
Abstract: Resume Objectifs Presenter les moyens disponibles pour affirmer l’obstruction sous-vesicale (OSV), leurs valeurs diagnostiques et pronostiques respectives et leurs indications. Methodes Une revue de la litterature a ete effectuee a l’aide de la base de donnees Medline/PubMed et SCOPUS recherchant les articles traitant de l’evaluation preoperatoire de l’obstruction sous-vesicale. Resultats L’indication d’une chirurgie de desobstruction est basee sur un faisceau d’arguments cliniques et selon les cas radiologiques, endoscopiques et urodynamiques. Outre l’examen clinique et la debitmetrie avec mesure du residu postmictionnel, l’echographie et l’endoscopie peuvent apporter des arguments en faveur d’une OSV. Bien que le bilan urodynamique ne soit pas systematique avant chirurgie de desobstruction (en particulier prostatique), l’etude pression debit reste le gold standard, l’OSV etant, en soi, un concept urodynamique. L’interpretation de l’etude pression debit se fait a l’aide du nomogramme de l’ICS chez l’homme avec calcul de l’index d’OSV (Bladder outlet obstruction index = PdetQmax−2 qmax). Chez la femme il n’existe pas de critere consensuel definissant l’OSV urodynamique. Bien que peu developpe en France, l’examen video-urodynamique qui associe la fluoroscopie au bilan urodynamique standard peut etre un outil d’interet dans la recherche preoperatoire d’une OSV. Plusieurs pistes d’alternatives non invasives a l’urodynamique ont ete evaluees au cours des dernieres annees comme le condom test, le penile cuff test ou les biomarqueurs urinaires mais restent tous du domaine de la recherche clinique. Conclusion L’affirmation de l’OSV en preoperatoire repose, stricto sensu, sur l’examen urodynamique avec etude pression debit, l’OSV etant en soi un concept urodynamique. Toutefois l’urodynamique n’est pas indique de maniere systematique avant chirurgie de desobstruction, notamment prostatique. L’examen clinique et la debitmetrie libre avec mesure du residu post-mictionnel restent les bases indispensables de l’evaluation d’une OSV a pratiquer de maniere systematique en preoperatoire.
Published: 2020

22. Rational and design of the ROTAS study: a randomized study for the optimal treatment of symptomatic patients with low-gradient severe aortic valve stenosis and preserved left ventricular ejection fraction

Author: Thierry Le Tourneau, Emmanuel Oger, Elena Galli, Catherine Sportouch, Augustin Coisne, Mathieu Lederlin, Anne Bernard, Erwan Donal, Florent Le Ven, Patrizio Lancellotti, Loïc Bière, Christophe Tribouilloy, Gilbert Habib, Service de cardiologie et maladies vasculaires [Rennes] = Cardiac, Thoracic, and Vascular Surgery [Rennes], CHU Pontchaillou [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Clinique du Millénaire - Oc Santé [Montpellier], Oc Santé [Montpellier], Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Timone [CHU - APHM] (TIMONE), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Service de cardiologie [Liège], CHU de Liège-Domaine Universitaire du Sart Tilman, Service de Cardiologie [Amiens], CHU Amiens-Picardie, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), PHRC-N 2017, National grant from « direction generale de la sante » -ministère de la santé, France, Service de cardiologie et maladies vasculaires, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Institut de Génomique Fonctionnelle - Montpellier GenomiX (IGF MGX), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Soins Intensifs et Urgences Cardiologiques, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Angers (UA), and Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)
Subjects: medicine.medical_specialty, Population, 030204 cardiovascular system & hematology, Doppler echocardiography, Severity of Illness Index, Ventricular Function, Left, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Aortic valve replacement, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Cardiac magnetic resonance imaging, Internal medicine, medicine, Humans, Randomized study, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Radiology, Nuclear Medicine and imaging, 030212 general & internal medicine, education, ComputingMilieux_MISCELLANEOUS, Heart Valve Prosthesis Implantation, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, education.field_of_study, Ejection fraction, medicine.diagnostic_test, business.industry, Aortic stenosis, Low gradient, Stroke Volume, Aortic Valve Stenosis, General Medicine, Stroke volume, Prognosis, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Stenosis, Treatment Outcome, Aortic Valve, Aortic valve stenosis, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Cardiology, Cardiology and Cardiovascular Medicine, business
Abstract: Aims Fifteen to thirty percentage of patients with severe aortic stenosis (AS) have preserved left ventricular ejection fraction (LVEF) and a discordant AS pattern at Doppler echocardiography, which is characterized by a small ( Methods and results The ROTAS trial will be a multicentre randomized non-blinded study involving 16 reference centres. AS severity will be confirmed by a multimodality approach (rest and stress echocardiography, calcium scoring, and cardiac magnetic resonance imaging for optimally characterize the population), which could provide important inputs to improve the pathophysiological understanding of this complex disease. Well-characterized patients will be randomized according to the management strategy. The primary endpoint will be the occurrence of all-cause mortality or cardiac related-hospitalizations during 2-year FU. One hundred and eighty subjects per group will be included. Conclusion The management of patients with LS severe AS and preserved LVEF is largely debated. ROTAS trial will allow a comprehensive evaluation of this particular pattern of AS and will establish which is the most appropriate management of these patients.
Published: 2020

23. Impact of point-spread function reconstruction on dynamic and static F-18-DOPA PET/CT quantitative parameters in glioma

Author: Madani François, Pierre-Jean Le Reste, Antoine Girard, Nibras Chaboub, Xavier Palard-Novello, Anne Devillers, Florence Le Jeune, Hervé Saint-Jalmes, Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), and Jonchère, Laurent
Subjects: Point spread function, [SDV.IB] Life Sciences [q-bio]/Bioengineering, PET-CT, Materials science, business.industry, kinetic, medicine.disease, point-spread function (PSF), gliomas, FDOPA, Glioma, medicine, Radiology, Nuclear Medicine and imaging, Original Article, [SDV.IB]Life Sciences [q-bio]/Bioengineering, positron emission tomography (PET), Nuclear medicine, business
Abstract: International audience; Background: Quantification of dynamic and static parameters extracted from 3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine (F-18-DOPA, FDOPA) positron emission tomography (PET)/computed tomography (CT) plays a critical role for glioma assessment. The objective of the present study was to investigate the impact of point-spread function (PSF) reconstruction on these quantitative parameters. Methods: Fourteen patients with untreated gliomas and investigated with FDOPA PET/CT were analyzed. The distribution of the 14 cases was as follows: 6 astrocytomas-isocitrate dehydrogenase-mutant; 2 oligodendrogliomas/1p19q-codeleted-isocitrate dehydrogenase-mutant; and 6 isocitrate dehydrogenase-wild-type glioblastomas. A 0-20-min dynamic images (8x15 sec, 2x30 sec, 2x60 sec, and 3x300 sec post-injection) and a 0-20-min static image were reconstructed with and without PSF. Tumoral volumes-of-interest were generated on all of the PET series and the background volumes-of-interest were generated on the 0-20-min static image with and without PSF. Static parameters (SUVmax and SUVmean) of the tumoral and the background volumes-of-interest and kinetic parameters (K1 and k2) of the tumoral volumes-of-interest extracted from using full kinetic analysis were provided. PSF and non-PSF quantitative parameters values were compared. Results: Thirty-three tumor volumes-of-interest and 14 background volumes-of-interest were analyzed. PSF images provided higher tumor SUVmax than non-PSF images for 23/33 VOIs [median SUVmax =3.0 (range, 1.4-10.2) with PSF vs. 2.7 (range, 1.4-9.1) without PSF; P
Published: 2022

24. Traitements antiparkinsoniens oraux, les pratiques infirmières en Ehpad

Author: Stéphanie, Mazé, Aline, Corvol, Manon, Auffret, CHU Pontchaillou [Rennes], Centre de Recherches sur l'Action Politique en Europe (ARENES), Université de Rennes (UR)-Institut d'Études Politiques [IEP] - Rennes-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Centre National de la Recherche Scientifique (CNRS), Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR), and Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR)
Subjects: [SDV]Life Sciences [q-bio], maladie de Parkinson, Administration, Oral, Parkinson Disease, nursing practice, Ehpad, pratique infirmière, therapeutic administration, administration thérapeutique, Antiparkinson Agents, Surveys and Questionnaires, Parkinson’s disease, Humans, Aged
Abstract: National audience; Complexe, chronique et d’évolution péjorative, la maladie de Parkinson nécessite un schéma thérapeutique personnalisé, centré sur l’administration régulière des traitements z La gestion de ceux-ci peut s’avérer délicate dans les établissements hébergeant des personnes âgées dépendantes, en particulier lorsque l’administration orale est difficile z Une enquête préliminaire a été menée afin de dresser un état des lieux des pratiques infirmières dans ces établissements.
Published: 2022

25. Altered epithelial barrier functions in the colon of patients with spina bifida

Author: Charlène Brochard, Guillaume Bouguen, Raphael Olivier, Tony Durand, Sébastien Henno, Benoît Peyronnet, Mael Pagenault, Chloé Lefèvre, Gaëlle Boudry, Mikael Croyal, Alain Fautrel, Maxime Esvan, Alain Ropert, Anne Dariel, Laurent Siproudhis, Michel Neunlist, CHU Pontchaillou [Rennes], The Enteric Nervous System in gut and brain disorders [U1235] (TENS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre référence maladies rares Spina Bifida, Service des Maladies de l'Appareil Digestif [CHU Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service d'anatomopathologie [Rennes], Hôpital Pontchaillou, Service d'urologie [Rennes] = Urology [Rennes], Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Mass Spectrometry Core Facility [Nantes] (CRNH-O ), Structure fédérative de recherche François Bonamy (Nantes Univ - SFR François Bonamy), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université (Nantes Univ), H2P2 - Histo Pathologie Hight Precision (H2P2), Université de Rennes (UR)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Marseille, and Bernard, Emilie
Subjects: Adult, Multidisciplinary, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Colon, Rectum, Colonoscopy, Coleoptera, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Surveys and Questionnaires, Animals, Humans, Spinal Dysraphism, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Our objectives were to better characterize the colorectal function of patients with Spina Bifida (SB). Patients with SB and healthy volunteers (HVs) completed prospectively a standardized questionnaire, clinical evaluation, rectal barostat, colonoscopy with biopsies and faecal collection. The data from 36 adults with SB (age: 38.8 [34.1–47.2]) were compared with those of 16 HVs (age: 39.0 [31.0–46.5]). Compared to HVs, rectal compliance was lower in patients with SB (p = 0.01), whereas rectal tone was higher (p = 0.0015). Ex vivo paracellular permeability was increased in patients with SB (p = 0.0008) and inversely correlated with rectal compliance (r = − 0.563, p = 0.002). The expression of key tight junction proteins and inflammatory markers was comparable between SB and HVs, except for an increase in Claudin-1 immunoreactivity (p = 0.04) in SB compared to HVs. TGFβ1 and GDNF mRNAs were expressed at higher levels in patients with SB (p = 0.02 and p = 0.008). The levels of acetate, propionate and butyrate in faecal samples were reduced (p = 0.04, p = 0.01, and p = 0.02, respectively). Our findings provide evidence that anorectal and epithelial functions are altered in patients with SB. The alterations in these key functions might represent new therapeutic targets, in particular using microbiota-derived approaches.Clinical Trials: NCT02440984 and NCT03054415.
Published: 2022

26. Common genetic variation in alcohol-related hepatocellular carcinoma: a case-control genome-wide association study

Author: Eric Trépo, Stefano Caruso, Jie Yang, Sandrine Imbeaud, Gabrielle Couchy, Quentin Bayard, Eric Letouzé, Nathalie Ganne-Carrié, Christophe Moreno, Abderrahim Oussalah, Cyrille Féray, Jean Frédéric Blanc, Bruno Clément, Patrick Hillon, Jérôme Boursier, Valérie Paradis, Julien Calderaro, Viviane Gnemmi, Jean-Charles Nault, Jean-Louis Guéant, Jacques Devière, Isabelle Archambeaud, Carole Vitellius, Bruno Turlin, Jean-Pierre Bronowicki, Thierry Gustot, Angela Sutton, Marianne Ziol, Pierre Nahon, Jessica Zucman-Rossi, Clément Meiller, Qian Cao, Théo Z. Hirsch, Sandra Rebouissou, Delphine Degré, Lukas Otero Sanchez, Nicolas Rosewick, Eric Quertinmont, Mireille Desille-Dugast, Muriel François-Vié, Cécile Moins, Emmanuelle Leteurtre, Guillaume Lassailly, Massih Ningarhari, Emmanuel Boleslawski, Vanessa Cottet, Université libre de Bruxelles (ULB), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), People's Hospital of Peking University (PKUPH), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital Paul Brousse, CHU Bordeaux [Bordeaux], Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Pontchaillou [Rennes], Centre de Ressources Biologiques Santé (CRB Santé), Université de Rennes (UR)-CHU Pontchaillou [Rennes]-CRLCC Eugène Marquis (CRLCC), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital Beaujon [AP-HP], Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor, Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), CHU Lille, Institut des Maladies de l'Appareil Digestif, Université de Nantes (UN), Hôtel-Dieu de Nantes, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), 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, Hôpitaux Universitaires Paris Seine-Saint-Denis [Sevran] (HUP2SD), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), BB-0033-00027, H2020 Marie Skłodowska-Curie Actions, MSCA, University Hospitals, UH: NCT03311152, Bpifrance, Agence Nationale de la Recherche, ANR: ANR-11-LABX-0021, Institut National de la Santé et de la Recherche Médicale, Inserm, Assistance Publique - Hôpitaux de Paris, AP-HP, Ligue Contre le Cancer, Fondation de France, Institut National Du Cancer, INCa, Université Libre de Bruxelles, Conseil régional de Bourgogne-Franche-Comté, Korean Association for the Study of the Liver, KASL, GENTHEP Consortium: Clément Meiller, Qian Cao, Théo Z Hirsch, Sandra Rebouissou, Delphine Degré, Lukas Otero Sanchez, Nicolas Rosewick, Eric Quertinmont, Mireille Desille-Dugast, Muriel François-Vié, Cécile Moins, Emmanuelle Leteurtre, Guillaume Lassailly, Massih Ningarhari, Emmanuel Boleslawski, Vanessa Cottet, ANR-11-LABX-0021,Lipstic,Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du cancer(2011), École pratique des hautes études (EPHE), Jonchère, Laurent, Laboratoires d'excellence - Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du cancer - - Lipstic2011 - ANR-11-LABX-0021 - LABX - VALID, 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-CRLCC Eugène Marquis (CRLCC), Faculté de Médecine [Bruxelles] [ULB], Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)], Biochimie – Biologie moléculaire et Nutrition [CHRU Nancy], Institut National de la Santé et de la Recherche Médicale [INSERM], Centre Hépato-Biliaire [Hôpital Paul Brousse] [CHB], Bordeaux Research In Translational Oncology [Bordeaux] [BaRITOn], Lipides - Nutrition - Cancer [Dijon - U1231] [LNC], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand [CHU Dijon], Centre Hospitalier Universitaire d'Angers [CHU Angers], Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques [HIFIH], Université Paris-Est Créteil Val-de-Marne - Paris 12 [UPEC UP12], Institut Mondor de Recherche Biomédicale [IMRB], Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER], Université Sorbonne Paris Nord, Centre Hospitalier Régional Universitaire de Nancy [CHRU Nancy], Nutrition-Génétique et Exposition aux Risques Environnementaux [NGERE], Nutrition, Métabolismes et Cancer [NuMeCan], Laboratoire de Recherche Vasculaire Translationnelle [LVTS (UMR_S_1148 / U1148)], Hôpital Européen Georges Pompidou [APHP] [HEGP], Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 [ONCO-THAI], and Equipe EPICAD (LNC - U1231)
Subjects: Adult, Male, Carcinoma, Hepatocellular, Genotype, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, Polymorphism, Single Nucleotide, Young Adult, [SDV.CAN] Life Sciences [q-bio]/Cancer, Wnt3A Protein, Humans, Genetic Predisposition to Disease, Aged, Aged, 80 and over, Liver Neoplasms, Genetic Variation, Middle Aged, Wnt Proteins, [SDV] Life Sciences [q-bio], Oncology, Case-Control Studies, Phospholipases A2, Calcium-Independent, Female, Alcohol-Related Disorders, Acyltransferases, Genome-Wide Association Study
Abstract: International audience; Background: Hepatocellular carcinoma is a frequent consequence of alcohol-related liver disease, with variable incidence among heavy drinkers. We did a genome-wide association study (GWAS) to identify common genetic variants for alcohol-related hepatocellular carcinoma. Methods: We conducted a two-stage case-control GWAS in a discovery cohort of 2107 unrelated European patients with alcohol-related liver disease aged 20–92 years recruited between Oct 22, 1993, and March 12, 2017. Cases were patients with alcohol-related hepatocellular carcinoma diagnosed by imaging or histology. Controls were patients with alcohol-related liver disease without hepatocellular carcinoma. We used an additive logistic regression model adjusted for the first ten principal components to assess genetic variants associated with alcohol-related hepatocellular carcinoma. We did another analysis with adjustment for age, sex, and liver fibrosis. New candidate associations (pandlt;1 × 10−6) and variants previously associated with alcohol-related hepatocellular carcinoma were evaluated in a validation cohort of 1933 patients with alcohol-related liver disease aged 29–92 years recruited between July 21, 1995, and May 2, 2019. We did a meta-analysis of the two case–control cohorts. Findings: The discovery cohort included 775 cases and 1332 controls. Of 7 962 325 variants assessed, we identified WNT3A-WNT9A (rs708113; p=1·11 × 10−8) and found support for previously reported regions associated with alcohol-related hepatocellular carcinoma risk at TM6SF2 (rs58542926; p=6·02 × 10−10), PNPLA3 (rs738409; p=9·29 × 10−7), and HSD17B13 (rs72613567; p=2·49 × 10−4). The validation cohort included 874 cases and 1059 controls and three variants were replicated: WNT3A-WNT9A (rs708113; p=1·17 × 10−3), TM6SF2 (rs58542926; p=4·06 × 10−5), and PNPLA3 (rs738409; p=1·17 × 10−4). All three variants reached GWAS significance in the meta-analysis: WNT3A-WNT9A (odds ratio 0·73, 95% CI 0·66–0·81; p=3·93 × 10−10), TM6SF2 (1·77, 1·52–2·07; p=3·84×10−13), PNPLA3 (1·34, 1·22–1·47; p=7·30 × 10−10). Adjustment for clinical covariates yielded similar results. We observed an additive effect of at-risk alleles on alcohol-related hepatocellular carcinoma. WNT3A-WNT9A rs708113 was not associated with liver fibrosis. Interpretation: WNT3A-WNT9A is a susceptibility locus for alcohol-related hepatocellular carcinoma, suggesting an early role of the Wnt–β-catenin pathway in alcohol-related hepatocellular carcinoma carcinogenesis.
Published: 2022

27. Les échelles anticholinergiques : usage en psychiatrie et mise à jour de l’échelle d’imprégnation anticholinergique

Author: Javelot, H, Meyer, G, Becker, G, Post, G, Runge, V, Pospieszynski, P, Schneiderlin, T, Armand-Branger, S, Michel, B, Weiner, L, Faria, C G F, Drapier, D, Fakra, E, Fossati, P, Haffen, E, Yrondi, A, Hingray, C, Etablissement Public de Santé Alsace Nord [EPSAN], Université de Strasbourg (UNISTRA), Laboratoire de Mathématiques et Modélisation d'Evry (LaMME), Université d'Évry-Val-d'Essonne (UEVE)-ENSIIE-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Santé Mentale Angevin (CESAME), CHU Strasbourg, Universidade Federal do Rio de Janeiro (UFRJ), Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR), Centre Hospitalier Guillaume Régnier [Rennes], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire de Nancy (CHU Nancy), Université d'Évry-Val-d'Essonne (UEVE), CHU Pontchaillou [Rennes]-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université européenne de Bretagne - European University of Brittany (UEB)-Institut des Neurosciences Cliniques de Rennes (INCR), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), and CHU Toulouse [Toulouse]
Subjects: Psychiatry, Échelle de médicaments anticholinergiques, Drug-Related Side Effects and Adverse Reactions, [SDV]Life Sciences [q-bio], Reproducibility of Results, Muscarinic Antagonists, Anticholinergiques, Xerostomia, Cholinergic Antagonists, Humans, Anticholinergic drug scale, Constipation, Anticholinergics, Aged, Antipsychotic Agents, Psychiatrie
Abstract: Anticholinergic properties are well known to prescribers, notably in mental health, as a therapeutic strategy for i.e. extrapyramidal syndrome but also as a source of numerous adverse side effects. Herein, we propose a narrative literature review describing: (i) cholinergic pharmacology and anticholinergic properties; (ii) the importance of anticholinergic therapeutic properties in psychiatry; (iii) the existing anticholinergic drug scales and their usage limitations in Psychiatry and; last (iv) an update to the anticholinergic drug impregnation scale, designed for the French psychiatry practice. The anticholinergic side effects can appear both in the peripheral level (dry mouth, constipation, etc.) and in the central level (especially as cognitive deficits). Many of the so called « anticholinergic » drugs are in fact entirely or mostly antimuscarinic and act essentially as parasympathetic system antagonists. Overall, anticholinergic/antimuscarinic side effects are usually attributed to psychotropic medications: to certain antipsychotics, notably classical neuroleptics such as phenothiazine and also to tricyclic antidepressants. In practice, the impact of anticholinergic toxicity treatments is often highlighted due to their excessively prolonged use in patients on antipsychotics. Interestingly, these antipsychotic treatments are better known for their anticholinergic side effects, especially cognitive ones, with an early onset specially in elder patients and/or in the case of polymedication. In order to evaluate anticholinergic side effects, metrics known as anticholinergic burden scales were created in the last few decades. Nowadays, 13 different scales are documented and accepted by the international academic community, but only three of them are commonly used: the Anticholinergic Drug Scale (ADS), the Anticholinergic Risk Scale (ARS) and the Anticholinergic Burden Scale (ACB). All of them are based on a similar principle, consisting of grading treatments individually, and they are normally scored from 0 - no presence of side effects - to 3 - anticholinergic effects considered to be strong or very strong. Using these scales enables the calculation of the so-called "anticholinergic burden", which corresponds to the cumulative effect of using multiple medications with anticholinergic properties simultaneously. The application of anticholinergic scales to patients with psychiatric disorders has revealed that schizophrenic patients seem to be especially sensitive to anticholinergic cognitive side effects, while elder and depressed patients were more likely to show symptoms of dementia when exposed to higher anticholinergic burden. Unfortunately, these tools appear to have a low parallel reliability, and so they might induce large differences when assessing side effects predictability. In addition, the capacity of these scales to predict central adverse effects is limited due to the fact they poorly or do not differentiate, the ability of treatments to cross the blood-brain barrier. Finally, one last limitation on the validity of these scales is prescription posology is not accounted for side effects considered to be dose dependent. Recently, the MARANTE (Muscarinic Acetylcholine Receptor ANTagonist Exposure) scale has incorporated an anticholinergic burden weighting by posology. Nevertheless, this new model can be criticized, due to the limited number of medications included and due to testing a limited number of potency ranges and dosages for each treatment. Herein, we propose an update to the Anticholinergic Impregnation Scale, developed specifically for the French Psychiatry practice. The scale validation was based on an evaluation of the prescriptions correcting anticholinergic peripheral side effects (constipation, xerostomia and xeropthalmia). This indirect evaluation allowed us to show patients with an anticholinergic impregnation score higher than 5 received significantly more treatments for constipation and xerostomia. This strategy bypasses the bias of a cognitive evaluation in patients with severe mental health disorders. Moreover, the relevance of a tool developed specifically for French psychiatry is justified by the fact that some highly prescribed treatments for mental illness in France (cyamemazine and tropatemine) are strong anticholinergics, and also by the fact they are rarely included in the existing anticholinergic scales. This update of the original scale, published in 2017, includes information whether prescribed drugs cross the blood-brain barrier and thus makes possible a more accurate assessment when evaluating anticholinergic central side effects. Finally, the anticholinergic impregnation scale will soon be integrated into a prescription help software, which is currently being developed to take into consideration dose dependent adverse effects.
Published: 2022

28. CD40L-expressing CD4+ T cells prime adipose-derived stromal cells to produce inflammatory chemokines

Author: Joelle Dulong, Séverine Loisel, Delphine Rossille, Simon Léonard, Nadège Bescher, Isabelle Bezier, Maelle Latour, Céline Monvoisin, Delphine Monnier, Nicolas Bertheuil, David Roulois, Karin Tarte, Jonchère, Laurent, Infrastructures - Développement d'une Plateforme Nationale pour la médecine régénératrice - - ECELLFRANCE2011 - ANR-11-INBS-0005 - INBS - VALID, Laboratoires d'excellence - Immunothérapies Grand Ouest - - IGO2011 - ANR-11-LABX-0016 - LABX - VALID, Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer (MOBIDIC), Université de Rennes (UR)-Etablissement français du sang [Rennes] (EFS Bretagne)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire SITI, CHU Pontchaillou [Rennes]-Etablissement Français du Sange Bretagne, CHU Pontchaillou [Rennes], This work is supported by the Infrastructure program EcellFRANCE (ANR-11-INBS-005). S.Le. is supported by the Labex IGO., ANR-11-INBS-0005,ECELLFRANCE,Développement d'une Plateforme Nationale pour la médecine régénératrice(2011), and ANR-11-LABX-0016,IGO,Immunothérapies Grand Ouest(2011)
Subjects: Cancer Research, Transplantation, obesity, IL-8, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cell Biology, adipose tissue, Oncology, neutrophils, [SDV.CAN] Life Sciences [q-bio]/Cancer, CD40, Immunology and Allergy, mesenchymal stromal cells, Genetics (clinical)
Abstract: International audience; The therapeutic potential of culture-adapted adipose-derived stromal cells (ASCs) is largely related to their production of immunosuppressive factors that are inducible in vitro by priming with inflammatory stimuli, in particular tumor necrosis factor-α (TNFα) and interferon-γ (IFNγ). In vivo, obesity is associated with chronic inflammation of white adipose tissue, including accumulation of neutrophils, infiltration by IFNγ/TNFα-producing immune cells, and ASC dysfunction. In the current study, we identified in obese patients a simultaneous upregulation of CD40Lin the adipose tissue stroma vascular fraction (AT-SVF), correlated with the Th1 gene signature, and an overexpression of CD40 by native ASCs. Moreover, activated CD4+ T cells upregulated CD40 on culture-expanded ASCs and triggered their production of IL-8 in a CD40L-dependent manner, leading to an increased capacity to recruit neutrophils. Finally, activation of ASCs by sCD40L or CD40L-expressing CD4+ T cells relies on both canonical and non-canonical NF-κB pathways, and IL-8 was found to be coregulated with NF-κB family members in AT-SVF. These data identify the CD40-CD40L axis as a priming mechanism of ASCs, able to modulate their cross talk with neutrophils in an inflammatory context, and their functional capacity for therapeutic applications.
Published: 2022

29. Continuous subcutaneous apomorphine infusion for the management of Parkinson's disease at the end-of-life

Author: Béreau, M, Giffard, M., Clairet, A. L., Tatu, L., Vérin, M., Auffret, Manon, CHU Pontchaillou [Rennes], Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], and Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR)
Subjects: continuous subcutaneous apomorphine infusion, Parkinson's disease, [SDV]Life Sciences [q-bio], end of life care
Abstract: International audience; Meeting Abstract PM1-040
Published: 2022

30. Terminal 6q deletions cause brain malformations, a phenotype mimicking heterozygous DLL1 pathogenic variants: A multicenter retrospective case series

Author: Marion Lesieur‐Sebellin, Marianne Till, Philippe Khau Van Kien, Bérénice Herve, Nicolas Bourgon, Céline Dupont, Anne‐Claude Tabet, Mathilde Barrois, Aurélie Coussement, Laurence Loeuillet, Eve Mousty, Vuthy Ea, Amal Assal, Laura Mary, Sylvie Jaillard, Claire Beneteau, Claudine Le Vaillant, Charles Coutton, Françoise Devillard, Carole Goumy, Amélie Delabaere, Sylvia Redon, Yves Laurent, Audrey Lamouroux, Jérôme Massardier, Catherine Turleau, Damien Sanlaville, Vincent Cantagrel, Pascale Sonigo, François Vialard, Laurent J. Salomon, Valérie Malan, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Biologie de la Reproduction, Environnement, Epigénétique & Développement (BREED), Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-École nationale vétérinaire d'Alfort (ENVA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), AP-HP Hôpital universitaire Robert-Debré [Paris], Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Maternité Port-Royal [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHI Poissy-Saint-Germain, CHU Pontchaillou [Rennes], École des Hautes Études en Santé Publique [EHESP] (EHESP), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre hospitalier universitaire de Nantes (CHU Nantes), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire [Grenoble] (CHU), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Groupe Hospitalier Bretagne Sud (GHBS), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), École nationale vétérinaire - Alfort (ENVA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Département de génétique [Robert Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital universitaire Robert-Debré [Paris], Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Service d'anatomie et cytologie pathologiques [Rennes] = Anatomy and Cytopathology [Rennes], Service de Cytogénétique et de Biologie Cellulaire, Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de Cytogénétique Médicale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Université de Brest (UBO), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de radiologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université Paris Cité (UPCité), Service Obstétrique [CHU Clermont-Ferrand], Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Thérapie guidée par l'image (TGI), and SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS)-SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, phenotype mimicking heterozygous, INTELLECTUAL DISABILITY, [SDV]Life Sciences [q-bio], Chromosome Disorders, Trisomy, LONG ARM, brain malformations, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, 03 medical and health sciences, Pregnancy, FETUSES, MICROARRAY ANALYSIS, Humans, pathogenic variants, Genetics (clinical), 030304 developmental biology, Retrospective Studies, 0303 health sciences, Virulence, DEVELOPMENTAL DELAY, ABNORMALITIES, 030305 genetics & heredity, Calcium-Binding Proteins, REARRANGEMENTS, Obstetrics and Gynecology, Membrane Proteins, deletions, 3. Good health, NOTCH, Phenotype, DIFFERENTIATION, Chromosomes, Human, Pair 6, Female, MENTAL-RETARDATION
Abstract: International audience; OBJECTIVE: Terminal 6q deletion is a rare genetic condition associated with a neurodevelopmental disorder characterized by intellectual disability and structural brain anomalies. Interestingly, a similar phenotype is observed in patients harboring pathogenic variants in the DLL1 gene. Our study aimed to further characterize the prenatal phenotype of this syndrome as well as to attempt to establish phenotype-genotype correlations. METHOD: We collected ultrasound findings from 22 fetuses diagnosed with a pure 6qter deletion. We reviewed the literature and compared our 22 cases with 14 fetuses previously reported as well as with patients with heterozygous DLL1 pathogenic variants. RESULTS: Brain structural alterations were observed in all fetuses. The most common findings (>70%) were cerebellar hypoplasia, ventriculomegaly, and corpus callosum abnormalities. Gyration abnormalities were observed in 46% of cases. Occasional findings included cerebral heterotopia, aqueductal stenosis, vertebral malformations, dysmorphic features, and kidney abnormalities. CONCLUSION: This is the first series of fetuses diagnosed with pure terminal 6q deletion. Based on our findings, we emphasize the prenatal sonographic anomalies, which may suggest the syndrome. Furthermore, this study highlights the importance of chromosomal microarray analysis to search for submicroscopic deletions of the 6q27 region involving the DLL1 gene in fetuses with these malformations.
Published: 2021

31. Apathy in depression: An arterial spin labeling perfusion MRI study

Author: Batail, Jean-Marie, Corouge, Isabelle, Combès, Benoit, Conan, Camille, Guillery-Sollier, Muriel, Vérin, Marc, Sauleau, Paul, Le Jeune, Florence, Gauvrit, Jean-Yves, Gauvrit, Jen-Yves, Robert, Gabriel, Barillot, Christian, Ferré, Jean-Christophe, Drapier, Dominique, Centre Hospitalier Guillaume Régnier [Rennes], Neuroimagerie: méthodes et applications (EMPENN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAL, IMAGE ET LANGAGE (IRISA-D6), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), Laboratoire de Psychologie : Cognition, Comportement, Communication (LP3C - EA1285), Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Université de Rennes 2 (UR2)-Institut Brestois des Sciences de l'Homme et de la Société (IBSHS), Université de Brest (UBO), CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire [Rennes], Centre Eugène Marquis (CRLCC), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Neuroradiology [Rennes], MRI data acquisition was supported by the Neurinfo MRI research facility from the University of Rennes I. Neurinfo is granted by the European Union (FEDER), the French State, the Brittany Council, Rennes Metropole, Inria, Inserm and the University Hospital of Rennes. This work has been funded by Institut des Neurosciences Cliniques de Rennes (INCR). The authors thank Mr Stéphane Brousse and Mr Jacques Soulabaille for their involvement in the conduct of the study., Corouge, Isabelle, Comportement et noyaux gris centraux - EA 4712, and Université de Rennes (UR)-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR)
Subjects: Psychiatry and Mental health, Depressive disorder, Arterial spin labeling, [SCCO.NEUR]Cognitive science/Neuroscience, Apathy, [SCCO.NEUR] Cognitive science/Neuroscience, Perfusion MRI, Neuroimaging, Biological Psychiatry
Abstract: International audience; IntroductionApathy, as defined as a deficit in goal-directed behaviors, is a critical clinical dimension in depression associated with chronic impairment. Little is known about its cerebral perfusion specificities in depression. To explore neurovascular mechanisms underpinning apathy in depression by pseudo-continuous arterial spin labeling (pCASL) magnetic resonance imaging (MRI).MethodsPerfusion imaging analysis was performed on 90 depressed patients included in a prospective study between November 2014 and February 2017. Imaging data included anatomical 3D T1-weighted and perfusion pCASL sequences. A multiple regression analysis relating the quantified cerebral blood flow (CBF) in different regions of interest defined from the FreeSurfer atlas, to the Apathy Evaluation Scale (AES) total score was conducted.ResultsAfter confound adjustment (demographics, disease and clinical characteristics) and correction for multiple comparisons, we observed a strong negative relationship between the CBF in the left anterior cingulate cortex (ACC) and the AES score (standardized beta = −0.74, corrected p value = 0.0008).ConclusionOur results emphasized the left ACC as a key region involved in apathy severity in a population of depressed participants. Perfusion correlates of apathy in depression evidenced in this study may contribute to characterize different phenotypes of depression.
Published: 2021

32. Dual role of EZH2 in megakaryocyte differentiation

Author: Rachel Petermann, Bruno Cassinat, Mathieu Vieira, Marie Cambot, William Vainchenker, Monika Wittner, Isabelle Plo, Philippe Dessen, Hana Raslova, Mira El Khoury, Najet Debili, Francesca Basso-Valentina, Valérie Edmond, Iléana Antony-Debré, Salwa BenAbdoulahab, Brahim Arkoun, Stefania Mazzi, Philippe Rameau, Virginie Dufour, Hématopoïèse normale et pathologique (U1170 Inserm), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cellules souches hématopoïétiques et développement des hémopathies myéloïdes (CSHMyelo), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Plateforme de Bioinformatique [Gustave Roussy], Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse (AMMICa), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut Jacques Monod (IJM (UMR_7592)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Microbiologie : Risques Infectieux, Université de Rennes (UR)-CHU Pontchaillou [Rennes]-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Université de Rennes - UFR d'Odontologie (UR Odontologie), Université de Rennes (UR)-Université de Rennes (UR), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université Paris Cité (UPCité), Gamétogenèse et Qualité du Gamète - ULR 4308 (GQG), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Lille, Institut National de la Transfusion Sanguine [Paris] (INTS), Service de Biologie Cellulaire [Saint-Louis], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Paris (UP)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-Faculté de Chirurgie Dentaire de Rennes-Faculté d'Odontologie-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université de Paris (UP)
Subjects: Blood Platelets, Megakaryocyte differentiation, [SDV]Life Sciences [q-bio], Immunology, macromolecular substances, Biochemistry, Thrombopoiesis, Small hairpin RNA, Mice, 03 medical and health sciences, 0302 clinical medicine, Megakaryocyte, Downregulation and upregulation, medicine, Animals, Humans, Enhancer of Zeste Homolog 2 Protein, Cells, Cultured, 030304 developmental biology, 0303 health sciences, Gene knockdown, biology, Chemistry, Kinase, Cell Biology, Hematology, Platelets and Thrombopoiesis, Cell biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, biology.protein, RNA Interference, Transcriptome, PRC2, Megakaryocytes, Chromatin immunoprecipitation
Abstract: EZH2, the enzymatic component of PRC2, has been identified as a key factor in hematopoiesis. EZH2 loss-of-function mutations have been found in myeloproliferative neoplasms, particularly in myelofibrosis, but the precise function of EZH2 in megakaryopoiesis is not fully delineated. Here, we show that EZH2 inhibition by small molecules and short hairpin RNA induces megakaryocyte (MK) commitment by accelerating lineage marker acquisition without change in proliferation. Later in differentiation, EZH2 inhibition blocks proliferation and polyploidization and decreases proplatelet formation. EZH2 inhibitors similarly reduce MK polyploidization and proplatelet formation in vitro and platelet levels in vivo in a JAK2V617F background. In transcriptome profiling, the defect in proplatelet formation was associated with an aberrant actin cytoskeleton regulation pathway, whereas polyploidization was associated with an inhibition of expression of genes involved in DNA replication and repair and an upregulation of cyclin-dependent kinase inhibitors, particularly CDKN1A and CDKN2D. The knockdown of CDKN1A and to a lesser extent CDKN2D could partially rescue the percentage of polyploid MKs. Moreover, H3K27me3 and EZH2 chromatin immunoprecipitation assays revealed that CDKN1A is a direct EZH2 target and CDKN2D expression is not directly regulated by EZH2, suggesting that EZH2 controls MK polyploidization directly through CDKN1A and indirectly through CDKN2D.
Published: 2021

33. Overlapping Phenotypes Associated With CYP24A1, SLC34A1, and SLC34A3 Mutations: A Cohort Study of Patients With Hypersensitivity to Vitamin D

Author: Arnaud Molin, Sandrine Lemoine, Martin Kaufmann, Pierre Breton, Marie Nowoczyn, Céline Ballandonne, Nadia Coudray, Hervé Mittre, Nicolas Richard, Amélie Ryckwaert, Alinoe Lavillaureix, Glenville Jones, Justine Bacchetta, Marie-Laure Kottler, Service de Génétique [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), Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Normandie Université (NU)-Normandie Université (NU), Œstrogènes, reproduction, cancer (OeReCa), Service de néphrologie, Groupement Hospitalier Edouard Herriot, Hospices Civils de Lyon, France (Service de néphrologie, Groupement Hospitalier Edouard Herriot, Hospices Civils de Lyon, France), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Queen's University [Kingston, Canada], Service de biochimie [CHU Caen], Département de Pédiatrie [Rennes] = Paediatrics [Rennes], CHU Pontchaillou [Rennes], Service de génétique clinique [Rennes], Université de Rennes (UR)-CHU Pontchaillou [Rennes]-hôpital Sud, Filières Maladies Rares ORKID et ERK-Net, Service de néphrologie rhumatologie dermatologie pédiatriques, Hôpital Femme Mère Enfant, Bron, France, parent, INSERM1033, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-hôpital Sud, and HUE, Erika
Subjects: Male, Endocrinology, Diabetes and Metabolism, 030232 urology & nephrology, vitamin D, medicine.disease_cause, Endocrinology, 0302 clinical medicine, Genotype, hypersensitivity to vitamin D, Medicine, Hypercalciuria, Child, Vitamin D3 24-Hydroxylase, Original Research, Aged, 80 and over, 0303 health sciences, Mutation, Middle Aged, 3. Good health, Phenotype, Child, Preschool, Female, Nephrocalcinosis, Hypophosphatemia, Adult, medicine.medical_specialty, Adolescent, Sodium-Phosphate Cotransporter Proteins, Type IIc, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Sodium-Phosphate Cotransporter Proteins, Type IIa, Diseases of the endocrine glands. Clinical endocrinology, SLC34A1 gene, Young Adult, 03 medical and health sciences, CYP24A1, Internal medicine, Vitamin D and neurology, Humans, Aged, 030304 developmental biology, Autosomal Recessive Infantile Hypercalcemia, business.industry, phosphate wasting diseases, Infant, Newborn, Infant, RC648-665, medicine.disease, CYP24A1- hydroxylase, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, SLC34A3 gene, Hypercalcemia, business, calcitriol induced hypercalcemia
Abstract: Mutations in CYP24A1 (vitamin D 24-hydroxylase) and SLC34A1 (renal phosphate transporter NPT2a) cause autosomal recessive Infantile Hypercalcemia type 1 and 2, illustrating links between vitamin D and phosphate metabolism. Patients may present with hypercalciuria and alternate between chronic phases with normal serum calcium but inappropriately high 1,25-(OH)2D and appropriately low PTH, and acute phases with hypercalcemia with suppressed PTH. Mutations in SLC34A3 and SLC9A3R1 have been associated with phosphate wasting without hypercalcemia. The aims of this study were to evaluate the frequency of mutations in these genes in patients with a medical history suggestive of CYP24A1 mutation to search for a specific pattern. Using next generation sequencing, we screened for mutations in 185 patients with PTH levels < 20 pg/mL, hypercalcemia and/or hypercalciuria, and relatives. Twenty-eight (15%) patients harbored biallelic mutations in CYP24A1 (25) and SLC34A3 (3), mostly associated with renal disease (lithiasis, nephrocalcinosis) (86%). Hypophosphatemia was found in 7 patients with biallelic mutations in CYP24A1 and a normal phosphatemia was reported in 2 patients with biallelic mutations in SLC34A3. Rare variations in SLC34A1 and SLC34A3 were mostly of uncertain significance. Fifteen patients (8%) carried only one heterozygous mutation. Heterozygous relatives carrying SLC34A1 or SLC34A3 variation may present with biochemical changes in mineral metabolism. Two patients’ genotype may suggest digenism (heterozygous variations in different genes). No variation was found in SLC9A3R1. As no specific pattern can be found, patients with medical history suggestive of CYP24A1 mutation should benefit from SLC34A1 and SLC34A3 analysis.
Published: 2021

34. A framework for validating AI in precision medicine: considerations from the European ITFoC consortium

Author: Tsopra, Rosy, Fernandez, Xose, Luchinat, Claudio, Alberghina, Lilia, Lehrach, Hans, Vanoni, Marco, Dreher, Felix, Sezerman, O Ugur, Cuggia, Marc, de Tayrac, Marie, Miklasevics, Edvins, Itu, Lucian Mihai, Geanta, Marius, Ogilvie, Lesley, Godey, Florence, Boldisor, Cristian Nicolae, Campillo-Gimenez, Boris, Cioroboiu, Cosmina, Ciusdel, Costin Florian, Coman, Simona, Hijano Cubelos, Oliver, Itu, Alina, Lange, Bodo, Le Gallo, Matthieu, Lespagnol, Alexandra, Mauri, Giancarlo, Soykam, H Okan, Rance, Bastien, Turano, Paola, Tenori, Leonardo, Vignoli, Alessia, Wierling, Christoph, Benhabiles, Nora, Burgun, Anita, Sezerman, O.Ugur, Soykam, H.Okan, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École pratique des hautes études (EPHE), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Institut Curie [Paris], Università degli Studi di Firenze = University of Florence (UniFI), Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Max Planck Institute for Molecular Genetics (MPIMG), Max-Planck-Gesellschaft, Alacris Theranostics GmbH [Berlin] (ATG), Acibadem University, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Riga Stradins University (RSU), Transilvania University of Brasov, Centre for Innovation in Medicine [Bucharest] (CIM), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), Centre de Ressources Biologiques Santé (CRB Santé), Université de Rennes (UR)-CHU Pontchaillou [Rennes]-CRLCC Eugène Marquis (CRLCC), EPIGENETICS Inc. BUDOTEK [Istanbul, Turkey], Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Paris-Saclay, This work was supported by the ITFoC project (Information Technology for the Future of Cancer) – FLAG-ERA support., Malbec, Odile, École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), INSERM, Université de Paris, Sorbonne Université, Centre de Recherche des Cordeliers, Information Sciences to support Personalized Medicine, 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), Tsopra, R, Fernandez, X, Luchinat, C, Alberghina, L, Lehrach, H, Vanoni, M, Dreher, F, Sezerman, O, Cuggia, M, de Tayrac, M, Miklasevics, E, Itu, L, Geanta, M, Ogilvie, L, Godey, F, Boldisor, C, Campillo-Gimenez, B, Cioroboiu, C, Ciusdel, C, Coman, S, Hijano Cubelos, O, Itu, A, Lange, B, Le Gallo, M, Lespagnol, A, Mauri, G, Soykam, H, Rance, B, Turano, P, Tenori, L, Vignoli, A, Wierling, C, Benhabiles, N, Burgun, A, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP)-École pratique des hautes études (EPHE), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), CHU Pontchaillou [Rennes]-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), Acibadem University Dspace, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-CRLCC Eugène Marquis (CRLCC)
Subjects: Artificial intelligence, MESH: Humans, MESH: Machine Learning, [SDV]Life Sciences [q-bio], Computer applications to medicine. Medical informatics, Precision medicine, Computerized decision support systems, R858-859.7, Cancer, Oncology, Personalized medicine, Algorithms, Humans, Machine Learning, Precision Medicine, Artificial Intelligence, Neoplasms, MESH: Algorithms, Computerized decision support system, MESH: Precision Medicine, [SDV] Life Sciences [q-bio], ComputingMethodologies_PATTERNRECOGNITION, MESH: Artificial Intelligence, [INFO]Computer Science [cs], MESH: Neoplasms, Research Article
Abstract: International audience; Abstract Background Artificial intelligence (AI) has the potential to transform our healthcare systems significantly. New AI technologies based on machine learning approaches should play a key role in clinical decision-making in the future. However, their implementation in health care settings remains limited, mostly due to a lack of robust validation procedures. There is a need to develop reliable assessment frameworks for the clinical validation of AI. We present here an approach for assessing AI for predicting treatment response in triple-negative breast cancer (TNBC), using real-world data and molecular -omics data from clinical data warehouses and biobanks. Methods The European “ITFoC (Information Technology for the Future Of Cancer)” consortium designed a framework for the clinical validation of AI technologies for predicting treatment response in oncology. Results This framework is based on seven key steps specifying: (1) the intended use of AI, (2) the target population, (3) the timing of AI evaluation, (4) the datasets used for evaluation, (5) the procedures used for ensuring data safety (including data quality, privacy and security), (6) the metrics used for measuring performance, and (7) the procedures used to ensure that the AI is explainable. This framework forms the basis of a validation platform that we are building for the “ITFoC Challenge”. This community-wide competition will make it possible to assess and compare AI algorithms for predicting the response to TNBC treatments with external real-world datasets. Conclusions The predictive performance and safety of AI technologies must be assessed in a robust, unbiased and transparent manner before their implementation in healthcare settings. We believe that the consideration of the ITFoC consortium will contribute to the safe transfer and implementation of AI in clinical settings, in the context of precision oncology and personalized care.
Published: 2021

35. Motor Symptom Asymmetry Predicts Non-motor Outcome and Quality of Life Following STN DBS in Parkinson's Disease

Author: Paul Sauleau, Claire Haegelen, Sophie Drapier, Jordan E. Pierce, Philippe Voruz, Kévin Ahrweiller, Marc Vérin, Julie Anne Peron, Dominique Drapier, Geneva University Hospitals and Geneva University, Centre Hospitalier Universitaire [Rennes], Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), 105314_182221, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, medicine.medical_specialty, Time Factors, Parkinson's disease, Deep Brain Stimulation, Apathy, Motor Disorders, Neuropsychological Tests, Outcome (game theory), Motor symptoms, Functional Laterality, Cognition, Quality of life (healthcare), Physical medicine and rehabilitation, Risk Factors, Subthalamic Nucleus, Surveys and Questionnaires, Humans, Medicine, Multidisciplinary, Verbal Behavior, business.industry, Parkinson Disease, Middle Aged, medicine.disease, nervous system diseases, surgical procedures, operative, nervous system, Quality of Life, Non motor, Female, [SDV.IB]Life Sciences [q-bio]/Bioengineering, business
Abstract: Risk factors for long-term non-motor symptoms and quality of life following subthalamic nucleus deep brain stimulation (STN DBS) have not yet been fully identified. In the present study, we investigated the impact of motor symptom asymmetry in Parkinson’s disease. Data were extracted for 52 patients with Parkinson’s disease (half with predominantly left-sided motor symptoms and half with predominantly right-sided ones) who underwent bilateral STN and a matched healthy control group. Performances for cognitive tests, apathy and depression symptoms, as well as quality-of-life questionnaires at 12 months post-DBS were compared with a pre-DBS baseline. Results indicated a deterioration in cognitive performance post-DBS in patients with predominantly left-sided motor symptoms. Performances of patients with predominantly right-sided motor symptoms were maintained, except for a verbal executive task. These differential effects had an impact on patients’ quality of life. The results highlight the existence of two distinct cognitive profiles of Parkinson’s disease, depending on motor symptom asymmetry. This asymmetry is a potential risk factor for non-motor adverse effects following STN DBS.
Published: 2021

36. Dynamics of cognitive action control in late-life depression during action selection

Author: Jean-Charles Roy, Gabriel Robert, Jean-François Houvenaghel, M. Guillery, Dominique Drapier, Joan Duprez, Centre Hospitalier Guillaume Régnier [Rennes], Centre Hospitalier Universitaire [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR)
Subjects: medicine.medical_specialty, Audiology, Action selection, Late-life depression, 050105 experimental psychology, 03 medical and health sciences, 0302 clinical medicine, Cognition, medicine, Reaction Time, Humans, 0501 psychology and cognitive sciences, Cognitive Dysfunction, Association (psychology), Biological Psychiatry, Geriatrics, Psychiatry, Depression, 05 social sciences, Action control, Simon task, Late life depression, Psychiatry and Mental health, Impulsive Behavior, Cognitive control, Facilitation, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Aversive Stimulus, Psychology, 030217 neurology & neurosurgery
Abstract: International audience; INTRODUCTION: Late-Life Depression (LLD) is characterized by deficits in cognitive control. We investigated the effect of LLD on a subset of cognitive control functions, the Cognitive Action Control (CAC), distinguishing on-line and adaptive control. METHODS: We compared LLD subjects (n = 31) and Healthy Controls (HC, n = 31) on their performance in a Simon task. The online congruency effect and adaptive effect were compared for reaction times (RT) and accuracy rates between the groups using mixed models. We applied distributional analyses of RT to differentiate the strength of impulsive action selection and the proficiency of selective action suppression. Finally, we measured correlations between the performances on the task and clinical scores of the LLD group. RESULTS: LLD had increased error rates in congruent trials compared to HC. Conversely, the adaptive CAC was equivalent between the groups. Distributional analyses showed that the fastest actions were less led by pertinent information in LLD. This phenomenon was found exclusively for congruent trials preceded by non-congruent trials. On the other hand, LLD patients, when they take time, were better than HC to suppress selectively non-relevant information. No difference was observed for adaptation to the preceding condition. No association between behavioral measurements and clinical scores were found. CONCLUSION: Our results suggest that LLD participants have a specific cognitive disturbance of CAC, showing less facilitation than HC in congruent situations. We propose that this originates in a difficulty in LLD patients in disengaging their attention from conflict situations, which is consistent with a biased CAC to aversive stimuli in depression.
Published: 2021

37. Spatio-temporal dynamics of large-scale electrophysiological networks during cognitive action control in healthy controls and Parkinson's disease patients

Author: Joan Duprez, Judie Tabbal, Mahmoud Hassan, Julien Modolo, Aya Kabbara, Ahmad Mheich, Sophie Drapier, Marc Vérin, Paul Sauleau, Fabrice Wendling, Pascal Benquet, Jean-François Houvenaghel, Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lebanese University [Beirut] (LU), Reykjavík University, MINDig, NeuroKyma, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), Centre Hospitalier Universitaire [Rennes], Bretagne Atlantique Ambition (BAA) as well as the Rennes Clinical Neuroscience Institute (INCR: www.incr.fr), and the Ille-et-Vilaine Parkinsonian Association (APIV), Jonchère, Laurent, and Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR)
Subjects: [SDV.IB] Life Sciences [q-bio]/Bioengineering, High density EEG, Cognitive Neuroscience, Simon task, Brain, Electroencephalography, Parkinson Disease, Magnetic Resonance Imaging, Dynamics, Functional connectivity, Cognition, Neurology, Cognitive control, Parkinson’s disease, Humans, Cognitive Dysfunction, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Networks
Abstract: International audience; Among the cognitive symptoms that are associated with Parkinson’s disease (PD), alterations in cognitive action control (CAC) are commonly reported in patients. CAC enables the suppression of an automatic action, in favor of a goal-directed one. The implementation of CAC is time-resolved and arguably associated with dynamic changes in functional brain networks. However, the electrophysiological functional networks involved, their dynamic changes, and how these changes are affected by PD, still remain unknown. In this study, to address this gap of knowledge, 10 PD patients and 10 healthy controls (HC) underwent a Simon task while high-density electroencephalography (HD-EEG) was recorded. Source-level dynamic connectivity matrices were estimated using the phase-locking value in the beta (12-25 Hz) and gamma (30-45 Hz) frequency bands. Temporal independent component analyses were used as a dimension reduction tool to isolate the task-related brain network states. Typical microstate metrics were quantified to investigate the presence of these states at the subject-level. Our results first confirmed that PD patients experienced difficulties in inhibiting automatic responses during the task. At the group-level, we found three functional network states in the beta band that involved fronto-temporal, temporo-cingulate and fronto-frontal connections with typical CAC-related prefrontal and cingulate nodes (e.g., inferior frontal cortex). The presence of these networks did not differ between PD patients and HC when analyzing microstates metrics, and no robust correlations with behavior were found. In the gamma band, five networks were found, including one fronto-temporal network that was identical to the one found in the beta band. These networks also included CAC-related nodes previously identified in different neuroimaging modalities. Similarly to the beta networks, no subject-level differences were found between PD patients and HC. Interestingly, in both frequency bands, the dominant network at the subject-level was never the one that was the most durably modulated by the task. Altogether, this study identified the dynamic functional brain networks observed during CAC, but did not highlight PD-related changes in these networks that might explain behavioral changes. Although other new methods might be needed to investigate the presence of task-related networks at the subject-level, this study still highlights that task-based dynamic functional connectivity is a promising approach in understanding the cognitive dysfunctions observed in PD and beyond.
Published: 2022

38. Food intake and weight loss of survival inpatients in the course of COVID-19 infection

Author: Laura Albaladejo, Maèva-Nauli Dusquesnoy, Caroline Martineau, Manon Philipponneau, M. Vaillant, Dorothée Romand, Véronique Laubé, Marie Behar, Jean-Luc Bosson, Karine Lambert, Lydiane Agier, Charlotte Nesseler, Thomas Lathière, Virginie Masdoua, Eric Fontaine, Najate Achamrah, Centre Hospitalier Universitaire [Grenoble] (CHU), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hospices Civils de Lyon, Departement de Neurologie (HCL), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Service d'endocrinologie diabétologie et nutrition [Rennes], Université de Rennes (UR)-CHU Pontchaillou [Rennes]-Hôpital Anne-de-Bretagne, Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Service de nutrition [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), CHU Saint-Antoine [AP-HP], CHU Tenon [AP-HP], Departement Hospitalo-Universitaire Hepatinov [Hôpital Paul Brousse - APHP], Hôpital Paul Brousse, Modélisation et Évaluation des données complexes en Santé Publique (TIMC-MESP), Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC ), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Laboratory of Fundamental and Applied Bioenergetics, Grenoble Alpes University, Grenoble, France, parent, douville, sabine, CHU Toulouse [Toulouse], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-Hôpital Anne-de-Bretagne, and Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, Pediatrics, medicine.medical_specialty, food intake, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, malnutrition, Overweight, Article, 03 medical and health sciences, Eating, 0302 clinical medicine, Interquartile range, Weight loss, medicine, Humans, pneumonia, 030212 general & internal medicine, Longitudinal Studies, ComputingMilieux_MISCELLANEOUS, 2. Zero hunger, Inpatients, Nutrition and Dietetics, business.industry, SARS-CoV-2, COVID-19, medicine.disease, Obesity, 3. Good health, Malnutrition, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Cohort, Lean body mass, Female, medicine.symptom, weight loss, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Cohort study
Abstract: NutriCoviD30 is a longitudinal multicenter cohort study that aimed to provide nutritional objective data of inpatients during COVID-19 infection. Food intake and weight trajectories, as well as clinical signs of the disease, pre-existing chronic diseases, and nutritional strategies were collected and analyzed during the course of the disease. Their association was estimated using mixed-effect regression modeling. Patients were recruited from French university hospitals from May until July 2020. For the 403 included patients (mean age 62.2 ± 14.2 years; 63% males), median [interquartile] hospitalization duration was 13 days [8; 20], and 30% of patients were admitted in intensive care unit. Patients declared a median 70% food intake decrease in the acute phase, and the disease resulted in an average loss of 8% of the pre-disease weight (corresponding to -6.5 kg). While most patients recovered their usual food intake one month after hospital discharge, they only regained half of their weight loss, such that malnutrition, which affected 67% of patients during their hospitalization, persisted in 41% of them. Patients with overweight, obesity and diabetes reported an additional weight loss of over 1.5% of their initial bodyweight during the hospitalization and recovery phase. In order to prevent malnutrition and its long-term effect, mainly combined with a rapid weight loss predominantly affecting lean body mass, implementation of nutritional support is needed for COVID-19 inpatients. It should start early in the course of the infection, and be extended up to the recovery phase., Graphical Abstract Image, graphical abstract
Published: 2021

39. Food addiction among morbidly obese patients: prevalence and links with obesity complications

Author: Aymery Constant, M. Som, Teycir Zayani, Romain Moirand, Ronan Thibault, David Val-Laillet, Estelle Le Pabic, Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-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), Service d'endocrinologie diabétologie et nutrition [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-Hôpital Anne-de-Bretagne, École des Hautes Études en Santé Publique [EHESP] (EHESP), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire [Rennes], Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Rennes (UR)-CHU Pontchaillou [Rennes]-Hôpital Anne-de-Bretagne, and Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, medicine.medical_specialty, Food addiction, Medicine (miscellaneous), 030209 endocrinology & metabolism, Context (language use), Morbidly obese, Yale Food Addiction Scale, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, Eating addiction, mental disorders, Prevalence, medicine, Humans, 030212 general & internal medicine, Psychiatry, Psychiatric Status Rating Scales, 2. Zero hunger, diabetes, business.industry, digestive, oral, and skin physiology, Obesity Surgery, Reproducibility of Results, Feeding Behavior, General Medicine, medicine.disease, Obesity, Obesity, Morbid, 3. Good health, obesity surgery, Psychiatry and Mental health, Clinical Psychology, Female, Food Addiction, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; In the context of obesity, little is known about the prevalence of food addiction nor about the phenotype of obese patients with food addiction. : To assess: (i) the prevalence of food addiction among obese patients eligible for obesity surgery; (ii) the relationship between clinical features and the complications of obesity. : Consecutive patients consulting for the first time were included. The Yale Food Addiction Scale (YFAS) 2.0 questionnaire was used to diagnose food addiction and its severity. Demographics, clinical features, and obesity complications were systematically collected. Statistics: Student's test was used for numerical variables and Chi-square test or Fisher's exact test for categorical variables. : A total of 292 patients were included: 79% female, age (mean ± SD) 42.6 ± 13.0 yrs., body mass index (BMI) 43.2 ± 6.8 kg/m. One hundred and eight patients (37%) had food addiction: 58% severe, 33% moderate, 9% mild. Food addiction prevalence was 39% (n = 61/156) among patients eligible for obesity surgery. Food addiction was more frequent among the unemployed, compared to professionally active patients (41.0% . 33.5%, p = 0.046). Clinical and metabolic phenotypes and obesity complications were similar between patients with and without food addiction. : Food addiction was present in 37% of obese patients, but was not associated with clinical features or obesity complications. Therefore, it should be systemically assessed for appropriate management.
Published: 2021

40. Development and Validation of a New Risk Prediction Score for Life-Threatening Ventricular Tachyarrhythmias in Laminopathies

Author: Mélanie Fradin, Nicolas Sadoul, Xavier Waintraub, Didier Klug, Albert Hagège, Pascal Sabouraud, Arnaud Isapof, Julien Durigneux, Olivier Lascols, Pascal Laforêt, Armelle Magot, Ivana Dabaj, Eloi Marijon, Camille Vatier, Pascal Cintas, Emmanuelle Salort, Bénédicte Gaborit, Antoine Muchir, Xavier Ferrer, Pascale Richard, Corinne Metay, Stéphane Boulé, Sarah Leonard-Louis, Philippe Mabo, V. Tiffreau, Caroline Stalens, Jitendra K. Vohra, Stéphane Schaeffer, Khadija Chikhaoui, Eric Bieth, Sandra Mercier, Pierre Ambrosi, Aleksandra Nadaj-Pakleza, Michèle Mayer, Katja Zeppenfeld, Gisèle Bonne, Véronique Manel, Jean-Marc Davy, Guilhem Sole, Ghassan Moubarak, Nicolas Lamblin, Klaus Dieterich, Christophe Meune, Abdallah Fayssoil, Arnaud Lazarus, Philippe Maury, Karim Wahbi, Philippe Petiot, Isabelle Jéru, Annick Toutain, Corinne Vigouroux, Ana Ferreiro, Maud Michaud, H.M. Bécane, Bruno Eymard, Thomas D. Gossios, Marie-Christine Vantyghem, Saurabh Kumar, Estelle Gandjbakhch, Yann Péréon, T. Thompson, Marie-Christine Minot-Myhié, Anthony Behin, Frédéric Sacher, Philippe Charron, Nicolas Combes, Julien Praline, Dominique Babuty, Emmanuelle Lagrue, Usha B. Tedrow, Jean-Marc Sellal, Florence Petit, Perry M. Elliott, Frédéric Anselme, Philippe Chevalier, Frederic Taithe, Christine Barnerias, Vincent Laugel, Andoni Echaniz-Laguna, Raphaël P. Martins, Alexander F.A. Androulakis, Rabah Ben Yaou, Franck Boccara, Ulrike Walther-Louvier, Tanya Stojkovic, Françoise Bouhour, Annachiara De Sandre-Giovannoli, Susana Quijano-Roy, Françoise Chapon, Jean-Noël Trochu, Céline Tard, Anne Rollin, Jean-Marie Cuisset, Denis Duboc, Raphaël Porcher, Catherine Sarret, Jonathan M. Kalman, Florence Demurger, Damien Bonnet, Christine Francannet, Neal K. Lakdawala, Romain Eschalier, Fabien Labombarda, Kostantinos Savvatis, Raul Juntas Morales, Isabelle Desguerre, Nicolas Lévy, Anne-Claire Brehin, Service de Cardiologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche en Myologie – U974 SU-INSERM, 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], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Rouen, Normandie Université (NU), St Bartholomew's Hospital (London), Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Association française contre les myopathies (AFM-Téléthon), IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Service de Cardiologie B, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Hôpital Ambroise Paré [AP-HP], William Harvey Research Institute, Barts and the London Medical School, Biostatistique et épidemiologie clinique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de cardiologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Filière Neuromusculaire (FILNEMUS), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Université de Caen Normandie (UNICAEN), Laboratoire d'Informatique Scientifique et Industrielle (LISI), Université de Poitiers-Ecole Nationale Supérieure de Mécanique et d'Aérotechnique [Poitiers] (ISAE-ENSMA), Hôpital Raymond Poincaré [AP-HP], CHU Lille, Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 (EGID), 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 National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Aix Marseille Université (AMU), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), 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), Service de cardiologie et maladies vasculaires [Rennes] = Cardiac, Thoracic, and Vascular Surgery [Rennes], CHU Pontchaillou [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinique Pasteur [Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), The Royal Melbourne Hospital, Leiden University Medical Center (LUMC), Universiteit Leiden, Service de neurologie pédiatrique [CHU Necker], Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], 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), CHU Necker - Enfants Malades [AP-HP], Hôpital Privé Le Bois Ramsay Santé [Lille], Service de génétique [Rouen], Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Mobilités : Vieillissement, Pathologie, Santé (COMETE), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Roger Salengro [Lille], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre de ressources biologiques Tissus ADN Cellules [Hôpital de la Timone - APHM] (CRB TAC), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Cytogénétique et de Biologie Cellulaire, Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire [Grenoble] (CHU), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Les Hôpitaux Universitaires de Strasbourg (HUS), CHU Clermont-Ferrand, Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de neurologie [Bordeaux], Service de Génétique Médicale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de chirurgie cadiovasculaire et thoracique [Rouen], Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Service de cardiologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Trousseau [APHP], Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), 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), CHU Strasbourg, Clinique Ambroise Paré [Centres Médico-Chirurgicaux Ambroise Pré, Pierre Cherest, Hartmann], Hôpital Cochin [AP-HP], Hospices Civils de Lyon (HCL), Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Lorraine (UL), Service de neurologie [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Centre Hospitalier Universitaire de Reims (CHU Reims), Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Neurologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Laboratoire d'étude de la motricité humaine - EA 3608 (LEMH), Université de Lille, Droit et Santé, Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Physiopathologie et thérapie du muscle strié, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Montréal (UdeM), Laboratoire Génie des procédés papetiers (LGP2 ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS), The Heart Hospital [London], University College of London [London] (UCL), This study was funded by grants from the AFM-Téléthon (French Alliance against Myopathies), which was not involved in the design and conduct of the study, collection, management, analysis, and interpretation of the data, preparation, review, or approval of the manuscript, and decision to submit the manuscript for publication. Some of this work was undertaken at University College London (United Kingdom) and St. Bartholomew’s Hospital (London, United Kingdom), which received a portion of funding from the United Kingdom Department of Health’s National Institute for Health Research Biomedical Research Centres funding scheme., Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Centre de recherche en myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP], CHU Bordeaux [Bordeaux]-Université Bordeaux Segalen - Bordeaux 2, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP], unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de cardiologie et maladies vasculaires, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], CHU Pitié-Salpêtrière [APHP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Unit of Neuromuscular Morphology [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [APHP]-Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de référence des maladies rares neuromusculaires Aquitaine-Grand Sud Ouest, CHU Bordeaux [Bordeaux], Laboratoire d'Informatique Scientifique et Industrielle (LISI / ENSMA), LISI-ENSMA, Service de Biochimie-Génétique [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Thérapie des maladies du muscle strié, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Cardiologie A, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Endocrinologie et Métabolisme, Unité de Cardiologie et Soins Intensifs, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Service de Génétique [Purpan], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Centre de Référence M3C Malformations Cardiaques Congénitales Complexes, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité-CHU Necker - Enfants Malades [AP-HP], Hôpital neurologique, Centre Hospitalier Universitaire de Lille (CHU de Lille), Service Neurologie Pédiatrique, Service de Neuropédiatrie, INSERM U836, équipe 4, Muscles et pathologies, Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Département de Neurologie, Hôpital Civil de Strasbourg, Groupe Myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de génétique médicale, CHU - HÔTEL-DIEU Clermont-Ferrand, CLAD Ouest, Centre Hospitalier Universitaire [Rennes], Centre recherche en CardioVasculaire et Nutrition (C2VN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Neuropédiatrie [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie et cerveau, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement (Inserm U1167 - RID-AGE - Institut Pasteur), Clinique Ambroise Paré, CHU Cochin [AP-HP], Epilepsie, sommeil et explorations fonctionnelles neuropédiatriques, Hospices Civils de Lyon (HCL)-Hopital Neurologique-Hôpital Femme Mère Enfant, Department of Medicine, Columbia University [New York]-College of Physicians and Surgeons, Service de neurologie, Hospices Civils de Lyon (HCL)-Hôpital de la Croix-Rousse [CHU - HCL], Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc - U837 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université Lille 2 - Faculté de Médecine, Hôpital de Rangueil, Institut Pascal - Clermont Auvergne (IP), Sigma CLERMONT (Sigma CLERMONT)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), laboratoire d'étude de la motricité humaine (LEMH EA3608), Université de Montréal - UdeM (CANADA), Laboratoire Génie des procédés papetiers (LGP2), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche en Myologie, 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], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité-CHU Necker - Enfants Malades [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), European Genomic Institute for Diabetes - FR 3508 (EGID), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, 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), Hôpital Purpan [Toulouse], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut de Myologie, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Tachycardia, medicine.medical_specialty, implantable, Accurate estimation, Ventricular Tachyarrhythmias, Validation Studies as Topic, 030204 cardiovascular system & hematology, tachycardia, Sudden death, LMNA, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, death, Physiology (medical), Internal medicine, defibrillators, medicine, Humans, In patient, 030212 general & internal medicine, sudden, [SDV.GEN]Life Sciences [q-bio]/Genetics, Prediction score, business.industry, Defibrillators, Implantable, ventricular, Tachycardia, Ventricular, Cardiology, Female, medicine.symptom, Cardiomyopathies, Cardiology and Cardiovascular Medicine, business
Abstract: Background: An accurate estimation of the risk of life-threatening (LT) ventricular tachyarrhythmia (VTA) in patients with LMNA mutations is crucial to select candidates for implantable cardioverter-defibrillator implantation. Methods: We included 839 adult patients with LMNA mutations, including 660 from a French nationwide registry in the development sample, and 179 from other countries, referred to 5 tertiary centers for cardiomyopathies, in the validation sample. LTVTA was defined as (1) sudden cardiac death or (2) implantable cardioverter defibrillator–treated or hemodynamically unstable VTA. The prognostic model was derived using the Fine-Gray regression model. The net reclassification was compared with current clinical practice guidelines. The results are presented as means (SD) or medians [interquartile range]. Results: We included 444 patients, 40.6 (14.1) years of age, in the derivation sample and 145 patients, 38.2 (15.0) years, in the validation sample, of whom 86 (19.3%) and 34 (23.4%) experienced LTVTA over 3.6 [1.0–7.2] and 5.1 [2.0–9.3] years of follow-up, respectively. Predictors of LTVTA in the derivation sample were: male sex, nonmissense LMNA mutation, first degree and higher atrioventricular block, nonsustained ventricular tachycardia, and left ventricular ejection fraction (https://lmna-risk-vta.fr). In the derivation sample, C-index (95% CI) of the model was 0.776 (0.711–0.842), and the calibration slope 0.827. In the external validation sample, the C-index was 0.800 (0.642–0.959), and the calibration slope was 1.082 (95% CI, 0.643–1.522). A 5-year estimated risk threshold ≥7% predicted 96.2% of LTVTA and net reclassified 28.8% of patients with LTVTA in comparison with the guidelines-based approach. Conclusions: In comparison with the current standard of care, this risk prediction model for LTVTA in laminopathies significantly facilitated the choice of candidates for implantable cardioverter defibrillators. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03058185.
Published: 2019

41. Hemodynamic Performances and Clinical Outcomes in Patients Undergoing Valve-in-Valve Versus Native Transcatheter Aortic Valve Implantation

Author: Alexandra Meilhac, Thomas Gandet, Claire Duflos, François Roubille, Laurent Schmutz, Frederic Targosz, Jean-Christophe Macia, Christophe Piot, Gabriel Robert, Eric Maupas, Benoit Lattuca, Mariama Akodad, Bernard Chevalier, Bernard Albat, Cécile Autissier, Delphine Delseny, Thierry Lefèvre, Florence Leclercq, Guillaume Cayla, François Rivalland, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Privé Jacques Cartier, Massy, France., Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Hôpital des Franciscaines, Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Saint Jean de Perpignan, Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), Clinique des Franciscaines, Nîmes, Service de chirurgie thoracique et cardio-vasculaire, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve-Université de Montpellier (UM), Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR), Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), and MORNET, Dominique
Subjects: Male, Reoperation, Aortic valve, medicine.medical_specialty, Time Factors, [SDV]Life Sciences [q-bio], Hemodynamics, Blood Pressure, Regurgitation (circulation), 030204 cardiovascular system & hematology, Prosthesis Design, Transcatheter Aortic Valve Replacement, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Clinical endpoint, Humans, In patient, 030212 general & internal medicine, Stroke, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Aged, 80 and over, Bioprosthesis, business.industry, Stroke Volume, Retrospective cohort study, Aortic Valve Stenosis, medicine.disease, [SDV] Life Sciences [q-bio], Stenosis, Treatment Outcome, medicine.anatomical_structure, Heart Valve Prosthesis, Cardiology, Female, Cardiology and Cardiovascular Medicine, business
Abstract: Valve-in-valve (ViV) transcatheter aortic valve implantation (TAVI) emerged has a less invasive treatment than surgery for patients with degenerated bioprosthesis. However, few data are currently available regarding results of ViV versus TAVI in native aortic valve. We aimed to compare hemodynamic performances and 1-year outcomes between patients who underwent ViV procedure and patients who underwent non-ViV TAVI. This bicentric study included all patients who underwent aortic ViV procedure for surgical bioprosthetic aortic failure between 2013 and 2017. All patients who underwent TAVI were included in the analysis during the same period. ViV and non-ViV patients were matched with 1:2 ratio according to size, type of TAVI device, age (±5 years), sex, and STS score. Primary end point was hemodynamic performance including mean aortic gradient and aortic regurgitation at 1-year follow-up. A total of 132 patients were included, 49 in the ViV group and 83 in the non-ViV group. Mean age was 82.8 ± 5.9 years, 55.3% were female. Mean STS score was 5.2% ± 3.1%. Self-expandable valves were implanted in 78.8% of patients. At 1-year follow-up, aortic mean gradient was significantly higher in ViV group (18.1 ± 9.4 mm Hg vs 11.4 ± 5.4 mm Hg; p0.0001) and 17 (38.6%) patients had a mean aortic gradient ≥20 mm Hg vs 6 (7.8%) in the non-ViV group (p = 0.0001). Aortic regurgitationgrade 2 were similar in both groups (p = 0.71). In the ViV group, new pacemaker implantation was less frequent (p = 0.01) and coronary occlusions occurred only in ViV group (n = 2 [4.1%]). At 1-year follow-up, 3 patients (2.3%) died from cardiac cause, 1 (2.1%) in the ViV group vs 2 (2.4%) in the non-ViV group (p = 0.9). There was no stroke. In conclusion, compared with TAVI in native aortic stenosis, ViV appears as a safe and feasible strategy in patients with impaired bioprosthesis. As 1-year hemodynamic performances seem better in native TAVI procedure, long-term follow-up should be assessed to determinate the impact of residual stenosis on outcomes and durability.
Published: 2019

42. Joint assessment of brain and spinal cord motor tract damage in patients with early RRMS: predominant impact of spinal cord lesions on motor function

Author: Haykel Snoussi, Gilles Edan, Anne Kerbrat, Elise Bannier, Jean-Christophe Ferré, Raphaël Chouteau, Benoît Combès, Christian Barillot, Paul Sauleau, Neuroimagerie: méthodes et applications (Empenn), Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE (IRISA-D5), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Service de Neurologie [CHU Rennes], CHU Pontchaillou [Rennes], Département de Radiologie [CHU de Rennes], Université de Rennes (UR), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurophysiologie [Rennes] = Neurophysiology [Rennes], Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR), Fondation pour l'Aide à la Recherche sur la Sclérose en Plaques, Empenn, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-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)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes]-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université européenne de Bretagne - European University of Brittany (UEB)-Institut des Neurosciences Cliniques de Rennes (INCR), Bannier, Elise, and Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR)
Subjects: Adult, Male, Pyramidal Tracts, Fluid-attenuated inversion recovery, Motor function, Cohort Studies, Multiple sclerosis, Lesion, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, 0302 clinical medicine, T2 lesions, medicine, Humans, In patient, Longitudinal Studies, 030212 general & internal medicine, [SDV.IB] Life Sciences [q-bio]/Bioengineering, Spinal cord, business.industry, Brain, Cervical Cord, Evoked Potentials, Motor, Magnetic Resonance Imaging, White Matter, Electrophysiology, medicine.anatomical_structure, Neurology, Motor Skills, Corticospinal tract, Female, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Neurology (clinical), medicine.symptom, Nuclear medicine, business, human activities, 030217 neurology & neurosurgery, MRI, Tractography
Abstract: International audience; BACKGROUND: In patients with MS, the effect of structural damage to the corticospinal tract (CST) has been separately evaluated in the brain and spinal cord (SC), even though a cumulative impact is suspected.OBJECTIVE: To evaluate CST damages on both the cortex and cervical SC, and examine their relative associations with motor function, measured both clinically and by electrophysiology.METHODS: We included 43 patients with early relapsing-remitting MS. Lesions were manually segmented on SC (axial T2*) and brain (3D FLAIR) scans. The CST was automatically segmented using an atlas (SC) or tractography (brain). Lesion volume fractions and diffusion parameters were calculated for SC, brain and CST. Central motor conduction time (CMCT) and triple stimulation technique amplitude ratio were measured for 42 upper limbs, from 22 patients.RESULTS: Mean lesion volume fractions were 5.2% in the SC portion of the CST and 0.9% in the brain portion. We did not find a significant correlation between brain and SC lesion volume fraction (r = 0.06, p = 0.68). The pyramidal EDSS score and CMCT were both significantly correlated with the lesion fraction in the SC CST (r = 0.39, p = 0.01 and r = 0.33, p = 0.03), but not in the brain CST.CONCLUSION: Our results highlight the major contribution of SC lesions to CST damage and motor function abnormalities.
Published: 2019

43. Time to blood culture positivity: An independent predictor of infective endocarditis and mortality in patients with Staphylococcus aureus bacteraemia

Author: V. Le Moing, Sandrine Barbas, Elodie Curlier, Hélène Jean-Pierre, Willem Vanwamel, Damien Fournier, Isabelle Patry, Eric Bellissant, Jacques Reynes, Sandrine Gohier-Treuvelot, François Alla, Catherine Chirouze, Fabienne Le Gac, Catherine Neuwirth, Philippe Géraud, François Goehringer, Christine Selton-Suty, Bruno Hoen, Virginie Sussmuth, Christine Delonca, Nathalie Keil, Catherine Sportouch, Thanh Doco-Lecompte, S. Tubiana, F. Vandenesch, Laetitia Minary, S. Desage, Catherine Leport, Hepher Malela, Cécile Descottes-Genon, Lionel Piroth, Christian Michelet, Pascale Rausch, Matthieu Revest, Bernard Iung, Jerome Etienne, Albert Sotto, Vincent Le Moing, J.-P. Lavigne, Catherine Cornu, Fernando Rivadeneira, Elise Thebault, Nathalie Bedos, Pierre-Yves Donnio, Lucie Vettoretti, Michèle Bes, S. Siméon, Jean-Christophe Eicher, Catherine Lechiche, X. Duval, François Vandenesch, Marie Célard, Pascal Chavanet, Sarah Tubiana, Raymond Ruimy, M.-L. Erpelding, Thierry May, André Pechinot, Nejla Aissa, Emila Ilic Habensus, François Delahaye, C.-A. Gustave, Lorraine Letranchant, Taissia Lelekov-Boissard, C. Chirouze, Anne Tristan, Audrey Coma, Jean-Philippe Lavigne, Xavier Duval, Pierre Tattevin, Alex van Belkum, Pierre Braquet, Marie-Line Erpelding, Pascale Longuet, Malika Hadid, Marie-Christine Greusard, Florence Galtier, Anne Verchère, P. Tattevin, Service des maladies infectieuses et réanimation médicale [Rennes] = Infectious Disease and Intensive Care [Rennes], CHU Pontchaillou [Rennes], Maladies Infectieuses [CHU de Montpellier], Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC1425 Bichat [AP-HP Hôpital Bichat - Claude Bernard] (INSERM), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Bactériologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Virulence bactérienne et maladies infectieuses (VBMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service de Microbiologie [CHU Caremeau, Nîmes], Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de référence des Staphylocoques [HCL, Lyon] (Institut des Agents Infectieux), Hospices Civils de Lyon (HCL), Laboratoire de Bactériologie [HCL, Lyon] (Institut des Agents Infectieux), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), ARN régulateurs bactériens et médecine (BRM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), VIRSTA/AEPEI Study Group. Chirouze C, Curlier E, Descottes-Genon C, Hoen B, Patry I, Vettoretti L, Chavanet P, Eicher JC, Gohier-Treuvelot S, Greusard MC, Neuwirth C, Péchinot A, Piroth L, Célard M, Cornu C, Delahaye F, Hadid M, Rausch P, Coma A, Galtier F, Géraud P, Jean-Pierre H, Le Moing V, Sportouch C, Reynes J, Aissa N, Doco-Lecompte T, Goehringer F, Keil N, Letranchant L, Malela H, May T, Selton-Suty C, Bedos N, Lavigne JP, Lechiche C, Sotto A, Duval X, Habensus EI, Iung B, Leport C, Longuet P, Ruimy R, Bellissant E, Donnio PY, Le Gac F, Michelet C, Revest M, Tattevin P, Thebault E, Alla F, Braquet P, Erpelding ML, Minary L, Tubiana S, Bès M, Etienne J, Lelekov-Boissard T, Tristan A, Vandenesch F, Van Belkum A, Rivadeneira F, Vanwamel W, Barbas S, Delonca C, Sussmuth V, Verchère A., Service des maladies infectieuses et réanimation médicale, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), CHU Caremeau, Nîmes, CIC-Nancy, Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy]-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Chrono-environnement - UFC (UMR 6249) (LCE), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Recherches Translationnelles sur le VIH et les maladies infectieuses (TransVIHMI), Université Montpellier 1 (UM1)-Institut de Recherche pour le Développement (IRD)-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Universtié Yaoundé 1 [Cameroun]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CIC Hôpital Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM)-UFR de Médecine-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques (U738 / UMR_S738), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), service de maladies infectieuses CHU J Minjoz Besancon, Hôpital Jean Minjoz, Centre National de référence des Staphylocoques, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL), Service des Maladies Infectieuses et Tropicales [Point-à-Pitre, Guadeloupe], CHU Pointe-à-Pitre/Abymes [Guadeloupe], Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Service de Cardiologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Biologie Laboratoire de Bacteriologie, Laboratoire de Microbiologie Médicale et Moléculaire, Université de Bourgogne (UB), Département d'infectiologie (CHU de Dijon), Evaluation et modélisation des effets thérapeutiques, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], 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)-Centre National de la Recherche Scientifique (CNRS)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-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)-Centre National de la Recherche Scientifique (CNRS)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), REseau national d'Investigation clinique en VACcinologie (REIVAC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP]-Hôtel-Dieu-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de Gestion des Essais de Produits de Santé (CeNGEPS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, Service de Bactériologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service des Maladies Infectieuses et Tropicales [CHRU Nancy], Service de Cardiologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Laboratoire universitaire d'antibiologie, Université Montpellier 1 (UM1), CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Bichat - Claude Bernard, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Microbiologie : Risques Infectieux, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-Faculté de Chirurgie Dentaire de Rennes-Faculté d'Odontologie-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service des maladies infectieuses, Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), CHU Montpellier, Service d'Epidémiologie et Evaluations Cliniques [CHRU Nancy] (Pôle S2R), Centre National de Reference des Staphylocoques, Université de Lyon, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Laboratoire Chrono-environnement (UMR 6249) (LCE), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Jonchère, Laurent
Subjects: Male, Methicillin-Resistant Staphylococcus aureus, 0301 basic medicine, Microbiology (medical), Staphylococcus aureus, bacteraemia, medicine.medical_specialty, Time Factors, Multivariate analysis, 030106 microbiology, Bacteremia, Independent predictor, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Blood culture, Prospective Studies, 030212 general & internal medicine, time to blood culture positivity, Prospective cohort study, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Aged, medicine.diagnostic_test, infective endocarditis, business.industry, Endocarditis, Bacterial, General Medicine, Middle Aged, Staphylococcal Infections, respiratory system, medicine.disease, mortality, 3. Good health, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious Diseases, Quartile, Blood Culture, Infective endocarditis, Female, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Objectives - Time to blood culture positivity (TTP), a routinely available parameter in automated blood culture systems, may be a proxy for infectious burden in patients with bloodstream infections. We aimed to study the association between TTP and infective endocarditis (IE), or death, in patients with Staphylococcus aureus bacteraemia. Methods - VIRSTA is a multicenter prospective cohort study that included all adult patients with S. aureus bacteraemia in eight university hospitals in France (2009-2011). We analyzed data from four centers which collected data on TTP. Regression models were used to study the association between TTP and definite IE (Duke-Li criteria), and 30 day-mortality. Results - We included 587 patients with S. aureus bacteraemia: mean age was 65.3±16.3 years, 420/587 patients (71.6%) were male, 121/587 (20.6%) died, and 42/587 (7.2%) had definite IE. Median TTP of first positive blood culture was 13.7 h (interquartile range, 9.9-18). On multivariate analysis, 30-day mortality was associated with TTP≤13.7 h (74/295 (25.1%) vs 47/292 (16.1%), P=0.02), as well as old age, McCabe score, methicillin resistance, stroke, pneumonia, and C-Reactive Protein. TTP was also independently associated with IE, but with a U-shape curve: IE was more common in the first (TTP18 h, 8/146, 5.5%) quartiles of TTP, P=0.002. Conclusions - TTP provides reliable information in patients with S. aureus bacteraemia, on the risk of IE, and prognosis, with short TTP being an independent predictor of death. This data readily available at no cost may be used to identify patients who require specific attention.
Published: 2019

44. Apathy alters emotional arousal in chronic schizophrenia

Author: Paul Sauleau, Thibaut Dondaine, Marc Vérin, Gabriel Robert, Dominique Drapier, Bruno Millet, Florence Le Jeune, Sophie Drapier, Pierre Philippot, Jean-Marie Batail, Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Catholique de Louvain = Catholic University of Louvain (UCL), Centre Hospitalier Guillaume Régnier [Rennes], Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR), CRLCC Eugène Marquis (CRLCC), CHU Pontchaillou [Rennes], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-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)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), Jonchère, Laurent, CHU Lille, CNRS, Inserm, and Université de Lille
Subjects: Adult, Male, Visual analogue scale, media_common.quotation_subject, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Apathy, Emotions, Executive Function, Young Adult, 03 medical and health sciences, 0302 clinical medicine, mental disorders, Schizophrenic Psychology, medicine, Humans, Pharmacology (medical), Valence (psychology), Young adult, Biological Psychiatry, media_common, Confounding, Case-control study, Galvanic Skin Response, 3. Good health, 030227 psychiatry, Psychiatry and Mental health, Feeling, Case-Control Studies, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Chronic Disease, Schizophrenia, Female, medicine.symptom, Arousal, Psychology, Photic Stimulation, 030217 neurology & neurosurgery, Research Paper, Clinical psychology
Abstract: International audience; BACKGROUND:Within the heterogeneity of schizophrenia, apathy constitutes an independent cluster of negative symptoms associated with poor outcomes. Attempts to identify an emotional deficit in patients who have schizophrenia with negative symptoms have yielded mixed results, and studies that focus on the relationship between apathy and emotional disorders are lacking.METHODS:We set out to remedy this shortcoming using a validated battery of film excerpts to induce positive and negative emotions in patients with chronic schizophrenia with (n = 20) or without (n = 20) apathy, and in controls (n = 20) comparable for age, sex and socioeconomic status. We assessed emotions using an innovative but validated technique to evaluate tonic and phasic electrodermal activity and subjective feelings using a standardized visual analogue scale.RESULTS:Using a qualitative measure of apathy, we did not find a specific decrease in tonic activity during the induction of positive emotions. However, we did observe that patients with apathy showed reduced tonic activity independent of valence (i.e., for both positive and negative emotions) compared with controls and patients without apathy. Moreover, the quantitative measure of apathy (Apathy Evaluation Scale) was the only significant factor, explaining 24% of the variance in tonic activity during induction of positive emotions after controlling for confounding factors.LIMITATIONS:Electrodermal activity was the only physiologic measure we acquired. We induced several emotions sequentially that might have overlapped with each other, but we added an emotional "washout" period and randomized the order of each film excerpt to limit this possibility.CONCLUSION:Taken together, these results suggest that apathy in schizophrenia could impair tonic activity during positive emotions. Treatments aimed at enhancing positive emotions may help alleviate apathy in schizophrenia.
Published: 2019

45. Algorithme de prise en charge des teignes de l’enfant après l’arrêt de la commercialisation de la griséofulvine en France

Author: Sophie Brun, Marie Beylot-Barry, Laurent Chouchana, Julie Toubiana, Sébastien Barbarot, Olivier Chosidow, Société Française de Mycologie Médicale, Marion Caseris, Jean Menotti, Nicolas Dupin, Jean-Pierre Gangneux, Françoise Botterel, Christelle Moreau, Bernard Guillot, Annabel Maruani, Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hôpital Robert Debré, Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Université Paris Cité (UPCité), Service de Parasitologie-Mycologie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Service de Parasitologie [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Nord, CHU Henri Mondor, Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL), Département de Pédiatrie et maladies infectieuses [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, Institut Pasteur [Paris]-Université Paris Cité (UPCité), Centre national de Référence des Corynebactéries du Complexe Diphtheriae - National Reference Center Corynebacteria of the diphtheriae complex (CNR), Département de Pharmacologie Clinique [CHU Cochin], Hôpital Cochin [AP-HP], Service de dermatologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Laboratoire Interdisciplinaire des Sciences du Numérique (LISN), CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Université Paris-Saclay, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de dermatologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], CHU Henri Mondor [Créteil], and Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)
Subjects: Teigne, Grisefuline, [SDV]Life Sciences [q-bio], Ocean Engineering, Safety, Risk, Reliability and Quality, Terbinafine
Abstract: Introduction Les teignes sont des dermatophyties frequentes touchant essentiellement l’enfant. En France, les dermatophytes en cause les plus prevalents appartiennent au genre Trichophyton puis Microsporum. La griseofulvine etait le seul traitement ayant une AMM chez les enfants, malgre un rapport benefice/risque suboptimal. Debut 2021, l’arret de sa commercialisation a conduit l’ANSM et les societes savantes a reevaluer dans l’urgence les options therapeutiques possibles. L’objectif de ce travail est de decrire les modalites d’elaboration d’un algorithme de prise en charge des enfants atteints de teigne comme alternative a la griseofulvine. Materiel et methodes A partir des donnees d’une revue non systematique de la litterature comprenant des recommandations europeennes et internationales, un groupe de travail coordonne par le centre de preuves (CDP) en dermatologie et integrant des membres des societes savantes impliquees: Societe francaise de dermatologie (SFD), Societe francaise de mycologie medicale (SFMM), Societe francaise de pediatrie (SFP), Societe francaise de dermatologie pediatrique (SFDP), Societe de pathologie infectieuse de langue francaise (SPILF), a elabore un algorithme de prise en charge des enfants atteints de teigne. Apres 5 reunions du groupe de travail entre le 23/4/2021 et le 15/6/2021, l’algorithme a ete propose a l’ANSM pour validation le 22/6/2021. Resultats Ce document propose un algorithme de prise en charge des teignes de l’enfant d’annexes. Les points-cles sont: – incitation au prelevement mycologique initial; – traitement probabiliste par terbinafine per os chez l’enfant d’au moins 10 kg; – en cas d’examen direct positif immediat en faveur d’un Microsporum : traitement par itraconazole d’emblee; – adaptation secondaire aux donnees de l’examen direct (passage vers l’itraconazole si Microsporum); – prise en charge hospitaliere chez l’enfant de – evaluation clinique a 4 semaines pour evaluer l’effet du traitement et eventuellement l’ajuster aux resultats des cultures mycologiques. Discussion L’arret de commercialisation d’un medicament unique dans son AMM comme la griseofulvine, perturbe considerablement la prise en charge des patients. Les societes savantes doivent rapidement proposer des alternatives fondees sur l’experience, les donnees des etudes observationnelles et les essais therapeutiques disponibles. Le CDP en dermatologie joue ce role, et a pu, en federant des representants des differentes societes savantes, proposer une alternative a court terme. Une demarche a moyen terme de validation reglementaire (mise en conformite des AMM) et de recherche (registre de suivi des enfants de moins de 10 kg, surveillance de la resistance a la terbinafine…) peut desormais debuter.
Published: 2021

46. Quantitative analysis and EEG markers of KCNT1 epilepsy of infancy with migrating focal seizures

Author: Emilie Carme, Anne de Saint Martin, Rima Nabbout, Cécile Laroche, Nathalie Villeneuve, Julien Modolo, Pascal Benquet, Fabrice Wendling, Anna Kaminska, Giulia Barcia, Edouard Hirsch, Paul Sauleau, Nicole Chemaly, Fanny Dubois, Mathieu Kuchenbuch, Agathe Roubertie, Matthieu Milh, Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Epilepsies de l'Enfant et Plasticité Cérébrale (U1129), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Université de Rennes (UR), Université Paris Descartes - Paris 5 (UPD5), Université Sorbonne Paris Cité (USPC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], CHU Strasbourg, CHU Grenoble, Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR), Hôpital de la Timone [CHU - APHM] (TIMONE), Poste d'accueil (thesis scholarship), PhD GRANT (poste d'accueil doctorant), Thesis Prize, Third year PhD Grant, 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), Université de Rennes (UNIV-RENNES), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Neurosciences Cliniques de Rennes (INCR)-CHU Pontchaillou [Rennes]-Université européenne de Bretagne - European University of Brittany (UEB)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
Subjects: Male, 0301 basic medicine, quantitative characterization, Nerve Tissue Proteins, Potassium Channels, Sodium-Activated, Electroencephalography, seizure propagation, 03 medical and health sciences, Epilepsy, Seizure onset, 0302 clinical medicine, developmental epileptic encephalopathy, medicine, Humans, In patient, Ictal, EEG markers, Early onset, medicine.diagnostic_test, business.industry, Infant, Newborn, Propagation pattern, Infant, medicine.disease, 030104 developmental biology, Phase coherence, Neurology, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Female, Epilepsies, Partial, Neurology (clinical), business, Neuroscience, 030217 neurology & neurosurgery, malignant migrating partial epilepsy of infancy
Abstract: International audience; Objective - We aimed to characterize epilepsy of infancy with migrating focal seizures (EIMFS), a rare, severe early onset developmental epilepsy related to KCNT1 mutation, and to define specific electroencephalography (EEG) markers using EEG quantitative analysis. The ultimate goal would be to improve early diagnosis and to better understand seizure onset and propagation of EIMFS as compared to other early onset developmental epilepsy. Methods - EEG of 7 EIMFS patients with KCNT1 mutations (115 seizures) and 17 patients with other early onset epilepsies (30 seizures) was included in this study. After detection of seizure onset and termination, spatiotemporal characteristics were quantified. Seizure propagation dynamics were analyzed using chronograms and phase coherence. Results - In patients with EIMFS, seizures started and were localized predominantly in temporal and occipital areas, and evolved with a stable frequency (4-10 Hz). Inter- and intrahemispheric migrations were present in 60% of EIMFS seizures with high intraindividual reproducibility of temporospatial dynamics. Interhemispheric migrating seizures spread in 71% from temporal or occipital channels to the homologous contralateral ones, whereas intrahemispheric seizures involved mainly frontotemporal, temporal, and occipital channels. Causality links were present between ictal activities detected under different channels during migrating seizures. Finally, time delay index (based on delays between the different ictal onsets) and phase correlation index (based on coherence of ictal activities) allowed discrimination of EIMFS and non-EIMFS seizures with a specificity of 91.2% and a sensitivity of 84.4%. Significance - We showed that the migrating pattern in EIMFS is not a random process, as suggested previously, and that it is a particular propagation pattern that follows the classical propagation pathways. It is notable that this study reveals specific EEG markers (time delay and phase correlation) accessible to visual evaluation, which will improve EIMFS diagnosis.
Published: 2018

47. Practical implementation of automated closed-loop insulin delivery: A French position statement

Author: Sylvia Franc, N Filhol, Yves Reznik, Pierre-Yves Benhamou, Jerome Place, C Guillot, Pauline Schaepelynck, A Desserprix, Anne Farret, E. Bonnemaison, Sophie Borot, Eric Renard, B. Delemer, D Durain, P. Serusclat, Marion Munch, Lucy Chaillous, Isabelle Guilhem, A. Penfornis, A. Sola-Gazagnes, N. Tubiana-Rufi, Sfd Sfd Paramedical Sfe Sfedp Ajd Ffd Fenarediam, Guillaume Charpentier, Jacques Beltrand, R. Leroy, Michael Joubert, Cnp-Edn, Bruno Guerci, Jean-Pierre Riveline, V. Melki, S Picard, C Abettan, C. Thivolet, Sandrine Lablanche, Hélène Hanaire, E. Bismuth, Nathalie Jeandidier, AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'endocrinologie, diabète, maladies métaboliques [Hôpital de la Conception - APHM], Aix Marseille Université (AMU), Centre Hospitalier Sud Francilien, CH Evry-Corbeil, Laboratoire de Biologie de l'Exercice pour la Performance et la Santé (LBEPS), Université d'Évry-Val-d'Essonne (UEVE)-Université Paris-Saclay-Institut de Recherche Biomédicale des Armées (IRBA), Centre d'Etudes et de Recherches pour l'Intensification du Traitement du Diabète (CERITD), Institut du thorax, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Endocrinologie - Diabétologie [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), CIC Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), CHU Necker - Enfants Malades [AP-HP], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service d'Endocrinologie - Diabète - Nutrition [Reims], Université de Reims Champagne-Ardenne (URCA)-Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Hôtel-Dieu Le Creusot, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d'Endocrinologie - Diabète - Nutrition [CHRU Nancy], Service d'endocrinologie diabétologie et nutrition [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-Hôpital Anne-de-Bretagne, Les Hôpitaux Universitaires de Strasbourg (HUS), Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), CHU Grenoble, Hôpital de Rangueil, CHU Toulouse [Toulouse], CHU Strasbourg, Point médical (Dijon), Hôpital Lariboisière-Fernand-Widal [APHP], Hôpital Cochin [AP-HP], Hospices Civils de Lyon (HCL), Centre d'études et de recherches pour l'intensification du traitement du diabète (CERITD), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre hospitalier universitaire de Nantes (CHU Nantes), Normandie Université (NU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Hôpital Gatien de Clocheville [Tours] (CHRU Tours), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), Université de Lorraine (UL), Université de Rennes (UR)-CHU Pontchaillou [Rennes]-Hôpital Anne-de-Bretagne, Université de Strasbourg (UNISTRA), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Paris-Saclay, Université de Toulouse (UT), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université d'Évry-Val-d'Essonne (UEVE)-Université Paris-Saclay-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Position statement, Adult, Adolescent, Endocrinology, Diabetes and Metabolism, education, Insulin delivery, Automated closed-loop insulin delivery, 030209 endocrinology & metabolism, Artificial pancreas, 030204 cardiovascular system & hematology, Adolescents, SFD, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Insulin Infusion Systems, Nursing, Internal Medicine, Humans, Hypoglycemic Agents, Insulin, Adults, Closed-loop, Child, Children, Statement (computer science), Health professionals, General Medicine, Therapeutic education, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 3. Good health, Clinical Practice, Diabetes Mellitus, Type 1, Organization of care, Type 1 diabetes, Technological advance, France, Psychology, Psychosocial, Closed loop
Abstract: International audience; Automated closed-loop (CL) insulin therapy has come of age. This major technological advance is expected to significantly improve the quality of care for adults, adolescents and children with type 1 diabetes. To improve access to this innovation for both patients and healthcare professionals (HCPs), and to promote adherence to its requirements in terms of safety, regulations, ethics and practice, the French Diabetes Society (SFD) brought together a French Working Group of experts to discuss the current practical consensus. The result is the present statement describing the indications for CL therapy with emphasis on the idea that treatment expectations must be clearly defined in advance. Specifications for expert care centres in charge of initiating the treatment were also proposed. Great importance was also attached to the crucial place of high-quality training for patients and healthcare professionals. Long-term follow-up should collect not only metabolic and clinical results, but also indicators related to psychosocial and human factors. Overall, this national consensus statement aims to promote the introduction of marketed CL devices into standard clinical practice.
Published: 2021

48. Functional Role of the Cerebellum in Parkinson Disease: A PET Study

Author: Joan Duprez, Jean-François Houvenaghel, Thibaut Dondaine, Gabriel Robert, Florence Le Jeune, Dominique Drapier, Paul Sauleau, Marc Vérin, Sophie Drapier, Audrey Riou, M. Guillery, Centre Hospitalier Universitaire [Rennes], Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], CHU Pontchaillou [Rennes]-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université européenne de Bretagne - European University of Brittany (UEB)-Institut des Neurosciences Cliniques de Rennes (INCR), Pharmacologie de la mort neuronale et de la plasticité cérébrale, IFR114-Université de Lille, Droit et Santé, Centre Hospitalier Guillaume Régnier [Rennes], and Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR)
Subjects: Adult, Male, Functional role, Cerebellum, [SDV]Life Sciences [q-bio], Thalamus, Supratentorial region, Behavioral Symptoms, Disease, Basal Ganglia, 050105 experimental psychology, Motor domain, 03 medical and health sciences, 0302 clinical medicine, Fluorodeoxyglucose F18, Basal ganglia, medicine, Humans, Cognitive Dysfunction, 0501 psychology and cognitive sciences, Aged, Cerebral Cortex, Principal Component Analysis, business.industry, 05 social sciences, Parkinson Disease, Cognition, Middle Aged, medicine.anatomical_structure, nervous system, Positron-Emission Tomography, Female, Neurology (clinical), Nerve Net, business, Neuroscience, 030217 neurology & neurosurgery
Abstract: ObjectivesTo test for cerebellar involvement in motor and nonmotor impairments in Parkinson disease (PD) and to determine patterns of metabolic correlations with supratentorial brain structures, we correlated clinical motor, cognitive, and psychiatric scales with cerebellar metabolism.MethodsWe included 90 patients with PD. Motor, cognitive, and psychiatric domains were assessed, and resting-state 18FDG-PET metabolic imaging was performed. The motor, cognitive, and psychiatric scores were entered separately into a principal component analysis. We looked for correlations between these 3 principal components and cerebellar metabolism. Furthermore, we extracted the mean glucose metabolism value for each significant cerebellar cluster and looked for patterns of cerebrum-cerebellum metabolic correlations.ResultsSeverity of impairment was correlated with increased metabolism in the anterior lobes and vermis (motor domain); the right crus I, crus II, and declive (cognitive domain); and the right crus I and crus II (psychiatric domain). No results survived multiple testing corrections regarding the psychiatric domain. Moreover, we found distributed and overlapping, but not identical, patterns of metabolic correlations for motor and cognitive domains. Specific supratentorial structures (cortical structures, basal ganglia, and thalamus) were strongly correlated with each of the cerebellar clusters.ConclusionsThese results confirm the role of the cerebellum in nonmotor domains of PD, with differential but overlapping patterns of metabolic correlations suggesting the involvement of cerebello-thalamo-striatal-cortical loops.
Published: 2021

49. Multimodal brain imaging connectivity analyses of emotional and motivational deficits in depression among women

Author: Isabelle Corouge, Magali Comte, Jean-Marie Batail, Lea Domain, Dominique Drapier, Eric Fakra, Gabriel Robert, Jean-Christophe Ferré, Elise Bannier, Thibaut Dondaine, Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], CHU Pontchaillou [Rennes]-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université européenne de Bretagne - European University of Brittany (UEB)-Institut des Neurosciences Cliniques de Rennes (INCR), Université de Rennes (UNIV-RENNES), Centre Hospitalier Guillaume Régnier [Rennes], Empenn, Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE (IRISA-D5), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-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)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes 1 (UR1), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), CHU Lille, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), Université de Rennes (UR), Neuroimagerie: méthodes et applications (Empenn), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Corouge, Isabelle, Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR), and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)
Subjects: Cerebellum, medicine.medical_specialty, Internal capsule, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Emotions, Neuroimaging, Audiology, Multimodal Imaging, behavioral disciplines and activities, Correlation, 03 medical and health sciences, 0302 clinical medicine, Dorsolateral Prefrontal Cortex, Fractional anisotropy, medicine, Cingulum (brain), Humans, Pharmacology (medical), Apathy, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Biological Psychiatry, Depressive Disorder, Major, Motivation, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, Brain, Middle Aged, medicine.disease, Magnetic Resonance Imaging, 030227 psychiatry, Psychiatry and Mental health, medicine.anatomical_structure, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Major depressive disorder, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, business, 030217 neurology & neurosurgery, Research Paper
Abstract: International audience; Background: Major depressive disorder (MDD) is characterized by impaired cortical–subcortical functional connectivity. Apathy adds to functional impairment, but its cerebral basis in MDD remains unknown. Our objective was to describe impairments in functional connectivity during emotional processing in MDD (with varying levels of congruency and attention), and to determine their correlation with apathy. Methods: We used the Variable Attention Affective Task during functional MRI, followed by diffusion-weighted MRI, to assess 55 right-handed women (30 with MDD and 25 healthy controls) between September 2012 and February 2015. We estimated functional connectivity using generalized psychophysiologic interaction and anatomic connectivity with tract-based spatial statistics. We measured apathy using the Apathy Evaluation Scale. Results: We found decreased functional connectivity between the left amygdala and the left anterior cingulate cortex (ACC) during negative stimuli in participants with MDD (t54 = 4.2; p = 0.035, family-wise error [FWE]–corrected). During high-attention stimuli, participants with MDD showed reduced functional connectivity between the right dorsolateral prefrontal cortex (dlPFC) and the right ACC (t54 = 4.06, pFWE = 0.02), but greater functional connectivity between the right dlPFC and the right amygdala (t54 = 3.35, p = 0.048). Apathy was associated with increased functional connectivity between the right dlPFC and the right ACC during high-attention stimuli (t28 = 5.2, p = 0.01) and increased fractional anisotropy in the right posterior cerebellum, the anterior and posterior cingulum and the bilateral internal capsule (all pFWE < 0.05). Limitations: Limitations included a moderate sample size, concomitant antidepressant therapy and no directed connectivity. Conclusion: We found that MDD was associated with impairments in cortical–subcortical functional connectivity during negative stimuli that might alter the recruitment of networks engaged in attention. Apathy-related features suggested networks similar to those observed in degenerative disorders, but possible different mechanisms.
Published: 2021

50. Fluoxetine for the Symptomatic Treatment of Multiple System Atrophy: The MSA-FLUO Trial

Author: Marc Vérin, Anne Pavy-Le Traon, Vanessa Rousseau, Margherita Fabbri, Alexandra Foubert-Samier, Wassilios G. Meissner, François Tison, Philippe Couratier, Agnès Sommet, Luc Defebvre, Valérie Cochen De Cock, Santiago Perez-Lloret, Franck Durif, Christine Tranchant, Claire Thalamas, Jean-Philippe Azulay, Philippe Remy, Jean-Christophe Corvol, Philippe Damier, Olivier Rascol, Jean-Luc Houeto, Christian Geny, Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), EuroMov - Digital Health in Motion (Euromov DHM), IMT - MINES ALES (IMT - MINES ALES), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Montpellier (UM), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), CHU Bordeaux [Bordeaux], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET), Hôpital de la Timone [CHU - APHM] (TIMONE), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Limoges, Centre hospitalier universitaire de Nantes (CHU Nantes), Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Clermont-Ferrand, Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne (UCA), Euromov (EuroMov), Université de Montpellier (UM), CHI Créteil, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), CHU Pontchaillou [Rennes], Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), NS-Park/FCRIN Network, UMS 015, Centre d’Excellence en Maladies Neurodégénératives (NeuroToul), CHU Toulouse [Toulouse], Clinique Beau Soleil [Montpellier], Pontifical Catholic University of Argentina (UCA), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Nord Laennec [CHU Nantes], Lille Neurosciences & Cognition - U 1172 (LilNCog), CHU Lille, CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Henri Mondor, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Les Hôpitaux Universitaires de Strasbourg (HUS), University of Otago [Dunedin, Nouvelle-Zélande], Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Henri Mondor [Créteil], and Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR)
Subjects: 0301 basic medicine, medicine.medical_specialty, Serotonin reuptake inhibitor, [SDV]Life Sciences [q-bio], multiple system atrophy, ENSAYO CLINICO, Placebo, law.invention, 03 medical and health sciences, NEUROBIOLOGIA, 0302 clinical medicine, Atrophy, Randomized controlled trial, Double-Blind Method, Rating scale, law, Internal medicine, Surveys and Questionnaires, medicine, ATROFIA MULTISISTÉMICA, Humans, symptomatic treatment, Fluoxetine, business.industry, Beck Depression Inventory, fluoxetine, ENFERMEDADES NEURODEGENERATIVAS, Parkinson Disease, clinical trial, medicine.disease, Confidence interval, 3. Good health, ENFERMEDAD DE PARKINSON, 030104 developmental biology, Treatment Outcome, Neurology, Quality of Life, placebo, TRATAMIENTO MEDICO, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug
Abstract: Fil: Rascol, Olivier. Universidad de Toulouse. Hospital Universitario de Toulouse; Francia Fil: Rascol, Olivier. Centro NeuroToul COEN; Francia Fil: Rascol, Olivier. Clínica de Toulouse. Centro de Investigación. Departamentos de Neurociencias y Farmacología Clínica; Francia Fil: Cochen De Cock, Valérie. Clínica Beau Soleil. Departamento de Neurología; Francia Fil: Cochen De Cock, Valérie. Universidad de Montpellier. EuroMov Digital Health in Motion; Francia Fil: Pavy-Le Traon, Anne. Centro de referencia de atrofia multisistémica; Francia Fil: Pavy-Le Traon, Anne. Universidad de Toulouse. Hospital Universitario de Toulouse. Instituto de Enfermedades Cardiovasculares y Metabólicas. Centro de Investigación Clínica de Toulouse. Departamento de Neurociencias; Francia Fil: Foubert-Samier, Alexandra. Universidad de Toulouse. Hospital Universitario de Toulouse. Instituto de Enfermedades Cardiovasculares y Metabólicas. Departamento de Neurociencias, Centro de investigación Clínica de Toulouse; Francia Fil: Thalamas, Claire. Universidad de Toulouse. Hospital Universitario de Toulouse. Centro de Investigación Clínica de Toulouse; Francia Fil: Thalamas, Claire. Hospital Universitario de Burdeos; Francia Fil: Sommet, Agnès. Red Francesa de Infraestructura de Investigación Clínica; Francia Fil: Pérez Lloret, Santiago. Universidad Abierta Interamericana. Centro de Investigaciones Biomédicas; Argentina Fil: Pérez Lloret, Santiago. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas; Argentina Fil: Fabbri, Margherita. Red Francesa de Infraestructura de Investigación Clínica; Francia Fil: Azulay, Jean Philippe. Universidad de Aix-Marsella. Sistema de Hospitales Universitarios Públicos de Marsella; Francia Fil: Corvol, Jean-Christophe. Universidad de la Sorbona; Francia Fil: Corvol, Jean-Christophe. Hospital de la Pitié-Salpêtrière; Francia Fil: Corvol, Jean-Christophe. Red Francesa de Infraestructura de Investigación Clínica; Francia Fil: Couratier, Philippe. Red Francesa de Infraestructura de Investigación Clínica; Francia Fil: Damier, Philippe. Hospital Nord Laennec. Centro de Investigación Clínica; Francia Fil: Defebvre, Luc. Universidad en Lille; Francia Fil: Defebvre, Luc. Hospital Universitario de Marsella. Departamento de Neurología y Patología del Movimiento; Francia Fil: Durif, Franck. Centro Hospitalario Universitario, Clermont-Ferrand. Departamento de Neurología; Francia Fil: Durif, Franck. Red Francesa de Infraestructura de Investigación Clínica; Francia Fil: Geny, Christian. Universidad de Montpellier. Departamento de Neurología; Francia Fil: Houeto, Jean-Luc. Centro Hospitalario Universitario de Limoges; Francia Fil: Houeto, Jean-Luc. Centro de referencia de atrofia multisistémica. Departamento de Neurología. Centro de Expertos en Parkinson; Francia Fil: Rascol, Olivier. Centro de referencia de atrofia multisistémica; Francia Fil: Remy, Philippe. Red Francesa de Infraestructura de Investigación Clínica. Centros Expertos en Parkinson; Francia Fil: Remy, Philippe. Instituto de Investigaciones Biomédicas Mondor; Francia Fil: Tranchant, Christine. Hospital Universitario de Estrasburgo. Red Francesa de Infraestructura de Investigación Clínica. Departamento de Neurología; Francia Fil: Verin, Marc. Universidad de Rennes. Hospital Universitario de Rennes. Red Francesa de Infraestructura de Investigación Clínica. Centro de expertos en Parkinson; Francia Fil: Tison, François. Centro de referencia de atrofia multisistémica. Departamento de Neurología de Enfermedades Neurodegenerativas; Francia Fil: Meissner, Wassilios G. Instituto de Investigación del Cerebro; Nueva Zelanda Fil: Meissner, Wassilios G. Universidad de Otago. Departamento de Medicina; Nueva Zelanda Abstract: Background: There are no effective treatments for multiple system atrophy (MSA). Objective: The objective of this study was to assess the efficacy and safety of the serotonin reuptake inhibitor fluoxetine (40 mg/d) for the symptomatic treatment of MSA. Methods: This was a double-blind, parallel-group, placebo-controlled, randomized trial in patients with "probable" MSA. The primary outcome was the change from baseline to week 12 in the mean total score of the Unified MSA Rating Scale (UMSARS Parts I + II). Secondary outcomes included change from baseline to week 6 in total UMSARS, and change from baseline to week 12 in the Scales for Outcomes in Parkinson Disease-Autonomic Dysfunction, Beck Depression Inventory, and different domains of the MSA-Quality of Life Questionnaire. Exploratory outcomes included change from baseline to week 12 in the UMSARS Parts I and II separately and change from baseline to week 24 in the total UMSARS score. Results: A total of 81 patients were randomly assigned, with no significant difference in the primary outcome (-2.13 units [95% confidence interval, CI, -4.55 to 0.29]; P = 0.08). There was a greater reduction on fluoxetine in the change from baseline to 12-week in UMSARS Part II (exploratory outcome: -1.41 units [95% CI, -2.84; 0.03]; p = 0.05) and in MSA-QoL emotional/social dimension (secondary outcome: -6.99 units [95% CI, -13.40; -0.56]; p < 0.03). A total of 5 deaths occurred (3 on fluoxetine and 2 on placebo). Conclusion: The MSA-FLUO failed to demonstrate fluoxetine superiority over placebo on the total UMSARS score, whereas trends in motor and emotional secondary/exploratory outcomes deserve further investigation.
Published: 2021

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