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1. Prediction of Iron Deficiency Anemia in Third Trimester of Pregnancy Based on Data in the First Trimester: A Prospective Cohort Study in a High-Income Country

Author: Anne-Sophie Resseguier, Candy Guiguet-Auclair, Anne Debost-Legrand, Anne-Françoise Serre-Sapin, Laurent Gerbaud, Françoise Vendittelli, Marc Ruivard, 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), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Service d’Hématologie Biologique [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], Pôle Santé Publique [CHU Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Réseau de Santé en Périnatalité d'Auvergne (RSPA), and Service de Médecine Interne [CHU Clermont-Ferrand]
Subjects: Nutrition and Dietetics, Anemia, Iron-Deficiency, Pregnancy Trimester, Third, hemoglobin, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, anemia, iron, pregnancy, Cohort Studies, Hemoglobins, Pregnancy Trimester, First, Hepcidins, Case-Control Studies, Ferritins, Receptors, Transferrin, Quality of Life, Humans, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Prospective Studies, Biomarkers, Food Science
Abstract: Background: Systematic iron supplementation may be harmful in pregnant women with non-depleted iron. Our objectives were to estimate the prevalence of anemia at the third trimester of pregnancy (T3) and to identify the parameters at the first trimester (T1), which best predict anemia at T3. Methods: This prospective cohort study in France included pregnant women at T1 without non-iron deficiency anemia. Clinical and social characteristics, health-related quality of life, blood count, and a frozen blood sample were collected at T1 and/or T3. Secondly, a matched nested case–control study was built for women with anemia at T3 but not at T1. Multivariate analyses and ROC curves were used to identify the best predictive parameter(s) of anemia at T3. Results: The prevalence of anemia at T3 in the cohort (629 women) was 21.9% (95% CI 18.7–25.2%). In the matched nested case–control study (256 women), hemoglobin (Hb), serum ferritin (SF) and the SF/soluble transferrin receptor ratio at T1 were predictive of anemia at T3 (p < 0.001); however, clinical and social characteristics, as serum hepcidin were not. In multivariate analyses, Hb at T1 was the best predictive biomarker of anemia at T3 with a cut-off value of 120 g/L (specificity 87.5%). Conclusions: The prevalence of anemia at the end of pregnancy remained high in a High-Income Country. Clinical, social, and biochemical parameters did not seem useful to predict anemia at T3 and could not guide iron supplementation. We suggest systematically performing a simple blood count in the first trimester of pregnancy and offering oral iron supplementation for women with Hb < 120 g/L.
Published: 2022
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2. Validation of a SARS-CoV-2 RT-PCR assay: a requirement to evaluate viral contamination in human semen

Author: Hélène Chabrolles, Hanae Pons-Rejraji, Laure Chaput, Amélie Brebion, Mélanie Fiot, Bruno Pereira, Florence Brugnon, Cécile Henquell, Service de Virologie Médicale et Moléculaire [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Laboratoire Microorganismes : Génome et Environnement (LMGE), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Centre d'Assistance Médicale à la Procréation [CHU Clermont-Ferrand] (AMP CECOS), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, and Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI)
Subjects: Male, Semen Analysis, Reproductive Medicine, Semen, Reverse Transcriptase Polymerase Chain Reaction, SARS-CoV-2, Obstetrics and Gynecology, Humans, RNA, Viral, COVID-19, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, Developmental Biology
Abstract: Is it possible to validate an accurate and reliable method for direct detection of SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR) in human semen fractions?This qualitative improvement study aimed to provide a prospective validation of SARS-CoV-2 detection in male semen. The SARS-CoV-2 genome was detected by multiplex real-time RT-PCR on patient samples that underwent routine semen analyses for infertility at the Center for Reproductive Medicine at the University Hospital of Clermont-Ferrand. Samples comprised surplus semen collected for treatment with assisted reproductive technology. Seminal fluid and spermatozoa fractions were isolated with density gradient centrifugation and cryopreserved. Positive samples were prepared with a standard of inactivated SARS-CoV-2 particles.The analytical method was validated in both seminal fluid and spermatozoa fractions. In both semen fractions, the assay was repeatable, reproducible and showed high sensitivity with a limit of detection of 0.33 SARS-CoV-2 genome copies/µl. The limit of quantification was 1 copy of the SARS-CoV-2 genome/µl. The method was effective regardless of semen quality (normal and altered sperm parameters), number of spermatozoa or the cryoprotectant media used to freeze spermatozoa.This validated RT-PCR assay provided accurate and reliable screening of SARS-CoV-2 in seminal fluid and spermatozoa fractions. This method is essential to ensure protection against viral contamination in the cryobanking process.
Published: 2022
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3. Atypical Borrelia garinii infection in an immunocompromised patient mimicking high-grade lymphoma

Author: Eiferman, Victor, Guenno, Guillaume Le, Boiret-Dupré, Nathalie, Barres, Bertrand, Luciani, Léa, Fournier, Pierre Edouard, Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Service d’Hématologie Biologique [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), and COMBE, Isabelle
Subjects: [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Abstract: International audience
Published: 2022
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4. Thrombin Generation and Cirrhosis

Author: Laurie Talon, Armand Abergel, Ton Lisman, Aurélien Lebreton, Thomas Sinegre, Thomas Lecompte, Service d’Hématologie Biologique [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Unité de Nutrition Humaine (UNH), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Genève (UNIGE), Service d'Hépatologie Gastro-entérologie [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, University of Groningen [Groningen], Groningen Institute for Organ Transplantation (GIOT), and Université de Genève = University of Geneva (UNIGE)
Subjects: Liver Cirrhosis, Male, 030204 cardiovascular system & hematology, Bioinformatics, Thrombomodulin, liver, HYPERCOAGULABILITY, 03 medical and health sciences, 0302 clinical medicine, LIVER-DISEASE, medicine, Coagulopathy, Humans, coagulation, Prothrombin time, VENOUS THROMBOEMBOLISM, COAGULOPATHY, medicine.diagnostic_test, business.industry, cirrhosis, Antithrombin, Thrombin, THROMBOMODULIN, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, medicine.disease, Coagulation, Hemostasis, thrombin generation, PROCOAGULANT IMBALANCE, hemostasis, PORTAL-VEIN THROMBOSIS, PROTEIN-C, 030211 gastroenterology & hepatology, Female, Cardiology and Cardiovascular Medicine, business, CRITICALLY-ILL PATIENTS, Protein C, medicine.drug, Partial thromboplastin time
Abstract: Epidemiological and laboratory studies performed in the last decades have changed our understanding of coagulopathy in cirrhosis, from a condition at increased risk of hemorrhagic events to one at higher thrombotic risk. However, it is not clear whether the decrease in factors that promote (except factor [F] VIII) versus inhibit coagulation in patients with cirrhosis results in a rebalanced state or in a hypercoagulable phenotype. This issue can be partially addressed using thrombin generation assays (TGA), which unlike routine clotting tests (prothrombin time or activated partial thromboplastin time) are sensitive to both procoagulant factors and coagulation inhibitors. However, many preanalytical issues and variable analytical methodologies used in TGAs complicate data analysis and interlaboratory comparisons. The introduction of TGAs in which activators of the protein C pathway (particularly soluble forms of thrombomodulin [TM]) are added has allowed detection of a reduced anticoagulant effect of TM or even a hypercoagulable phenotype as judged by endogenous thrombin potential. However, inter- and intra-assay variability may be greater with this TGA variant compared with “standard” TGAs. TGAs also allowed identifying main determinants of the hypercoagulability phenotype in the presence of TM: acquired antithrombin and protein C deficiencies, and elevated FVIII levels. The aim of this narrative review is to summarize the preanalytical and methodological variables of TGAs and also the findings of the main studies that have evaluated TGAs in patients with cirrhosis. The review also provides some propositions for future studies and outlines some perspectives on the potential implementation of this promising tool in clinical practice for the study of coagulation in patients with cirrhosis.
Published: 2020
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5. Multiple sclerosis as differential diagnosis of radionecrosis for post-irradiation brain lesions: A case report

Author: Julian Biau, Pierre Clavelou, Florent Guillemin, Sakahlé Condé, G. Dupic, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Service de Neurologie [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, CHU Gabriel Montpied [Clermont-Ferrand], and CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand]
Subjects: medicine.medical_specialty, Pituitary macroadenoma, [SDV]Life Sciences [q-bio], GTV, gross tumor volume, medicine.medical_treatment, R895-920, MRI, magnetic resonance imagery, BED, biologically effective dose, [SDV.CAN]Life Sciences [q-bio]/Cancer, Gy, gray, CSF, cerebrospinal fluid, Article, 030218 nuclear medicine & medical imaging, Multiple sclerosis, Medical physics. Medical radiology. Nuclear medicine, 03 medical and health sciences, 0302 clinical medicine, Cerebrospinal fluid, medicine, Radiology, Nuclear Medicine and imaging, Medical diagnosis, CTV, clinical target volume, Dosimetric analysis, RC254-282, ComputingMilieux_MISCELLANEOUS, VMAT, volumetric modulated arctherapy, Past medical history, Radiotherapy, business.industry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, IMRT, intensity modulated radiotherapy, medicine.disease, CT, computed tomography, 3. Good health, Radiation therapy, Oncology, 030220 oncology & carcinogenesis, LS, Lhermitte’s syndrome, Brain lesions, Differential diagnosis, Radiology, business, PTV, planning target volume
Abstract: Highlights • No correlation between radiotherapy and the development of MS is to date described. • Demyelination can occur after radiotherapy in tissue adjacent to irradiated tumours. • MS lesions seem to occur in regions irradiated with a mean BED2 of 34 Gy. • Caution is needed among 35 - 45-year-old patients or with demyelinating illnesses. • MS should be kept in mind as differential diagnosis of metastases or radionecrosis., Introduction Demyelination can occur after brain radiotherapy in tissue adjacent to irradiated tumours. To date, no correlation has been found between conventional-dose radiotherapy and the development of multiple sclerosis, but radiotherapy could be a triggering factor among women with known multiple sclerosis. To the best of our knowledge, this is the first well-documented case of this association with a dosimetric analysis. Case presentation The case we report here describes the development of multiple sclerosis in a 36-year-old woman without significant past medical history 3 months after the last session of fractionated stereotactic radiotherapy for a pituitary macroadenoma. Our dosimetric analysis suggests that all the multiple sclerosis lesions occurred in the brain regions irradiated with a mean biologically effective dose (BED2) of 33.9 Gy (27.3–49.6 Gy). Conclusion Consequently special caution towards radiotherapy is required among patients with demyelinating illnesses or for 35–45-year-old women who are at risk. In addition, multiple sclerosis lesions can look like metastases. We should therefore keep differential diagnoses in mind in order not to make mistakes that would delay treatment.
Published: 2020
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6. Colorectal Cancer Survivors Suffering From Sensory Chemotherapy-Induced Peripheral Neuropathy Are Not a Homogenous Group: Secondary Analysis of Patients’ Profiles With Oxaliplatin-Induced Peripheral Neuropathy

Author: Nicolas Kerckhove, Marie Selvy, Céline Lambert, Coralie Gonneau, Gabrielle Feydel, Caroline Pétorin, Agnès Vimal-Baguet, Sergey Melnikov, Sharif Kullab, Mohamed Hebbar, Olivier Bouché, Florian Slimano, Vincent Bourgeois, Valérie Lebrun-Ly, Frédéric Thuillier, Thibault Mazard, David Tavan, Kheir Eddine Benmammar, Brigitte Monange, Mohamed Ramdani, Denis Péré-Vergé, Floriane Huet-Penz, Ahmed Bedjaoui, Florent Genty, Cécile Leyronnas, Jérôme Busserolles, Sophie Trévis, Vincent Pinon, Denis Pezet, David Balayssac, Neuro-Dol (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), CHU Clermont-Ferrand, Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), Institut Analgesia, Service de Chirurgie Digestive et Hépatobiliaire [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre Hospitalier Saint-Flour (CH Saint-Flour), Centre hospitalier Moulins-Yzeure [Moulins] (CH Moulins-Yzeure), Service d'oncologie médicale (CHRU Lille), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire de Reims (CHU Reims), Biospectroscopie Translationnelle - EA 7506 (BIOSPECT), Université de Reims Champagne-Ardenne (URCA), Centre Hospitalier Boulogne-sur-mer, Service d'Oncologie médicale [CHU Limoges], CHU Limoges, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Clinique de l'Infirmerie Protestante de Lyon (CIPL), Centre Hospitalier Emile Roux [Le Puy-en-Velay] (CH Le Puy-en-Velay), Centre Hospitalier de Béziers, Centre hospitalier Saint Joseph - Saint Luc [Lyon], Centre Hospitalier Alpes-Léman - CHAL, Centre Hospitalier Intercommunal Les Hôpitaux du Léman (CHI Les Hôpitaux du Léman), Centre Hospitalier de Vichy (CH Vichy), Groupe Hospitalier Mutualiste de Grenoble (GHM), Service Pharmacie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], and CHU Clermont-Ferrand-CHU Louise Michel [Clermont-Ferrand]
Subjects: Oncology, medicine.medical_specialty, oxaliplatin, Colorectal cancer, colorectal cancer, RM1-950, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Internal medicine, Medicine, Pharmacology (medical), 030212 general & internal medicine, Original Research, Pharmacology, neuropathic pain, business.industry, Cancer, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, medicine.disease, 3. Good health, Oxaliplatin, Peripheral neuropathy, Chemotherapy-induced peripheral neuropathy, 030220 oncology & carcinogenesis, Cohort, Anxiety, Therapeutics. Pharmacology, medicine.symptom, business, medicine.drug, chemotherapy-induced peripheral neuropathy, cluster analysis
Abstract: International audience; Oxaliplatin, a pivotal drug in the management of colorectal cancer, causes chemotherapy-induced peripheral neuropathy (CIPN) in a third of cancer survivors. Based on a previous cross-sectional study assessing oxaliplatin-related sensory CIPN in colorectal cancer survivors, a secondary analysis was designed to explore the possibility that different clusters of patients may co-exist among a cohort of patients with oxaliplatin-related CIPN. Other objectives were to characterize these clusters considering CIPN severity, anxiety, depression, health-related quality of life (HRQOL), patients’ characteristics and oxaliplatin treatments. Among the 96 patients analyzed, three clusters were identified (cluster 1: 52, cluster 2: 34, and cluster 3: 10 patients). Clusters were significantly different according to CIPN severity and the proportion of neuropathic pain (cluster 1: low, cluster 2: intermediate, and cluster 3: high). Anxiety, depressive disorders and HRQOL alteration were lower in cluster 1 in comparison to clusters 2 and 3, but not different between clusters 2 and 3. This study underlines that patients with CIPN are not a homogenous group, and that CIPN severity is associated with psychological distress and a decline of HRQOL. Further studies are needed to explore the relation between clusters and CIPN management.
Published: 2021
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7. Rhinovirus Infection and Familial Atopy Predict Persistent Asthma and Sensitisation 7 Years after a First Episode of Acute Bronchiolitis in Infancy

Author: Valérie Julian, Alexandra Usclade, Flore Amat, Carole Egron, Emmanuelle Rochette, Julie Magnier, Aurélien Mulliez, Bertrand Evrard, Service de Pédiatrie Générale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service Médecine du Sport et Explorations Fonctionnelles [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), Centre d'Investigation Clinique [CHU Clermont-Ferrand] (CIC 1405), Institut National de la Santé et de la Recherche Médicale (INSERM)-Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), Service d'Immunologie [CHU Clermont-Ferrand], Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Hôpital Robert Debré Paris, Hôpital Robert Debré, Dept Sport Med and Funct Explorat, and ROSSI, Sabine
Subjects: medicine.medical_specialty, Allergy, acute bronchiolitis, respiratory syncytial virus, [SDV]Life Sciences [q-bio], atopy, medicine.disease_cause, Pediatrics, Article, RJ1-570, Atopy, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, Internal medicine, medicine, Respiratory function, 030212 general & internal medicine, Asthma, First episode, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, business.industry, Atopic dermatitis, asthma, medicine.disease, 3. Good health, rhinovirus, 030228 respiratory system, Bronchiolitis, Pediatrics, Perinatology and Child Health, Rhinovirus, business
Abstract: Background: We set out to assess the risk factors for asthma outcome in a cohort of infants who experienced their first episode of acute bronchiolitis. Methods: A cohort of 222 infants who were included during a first episode of acute bronchiolitis was prospectively followed. Herein, we present the results of their assessments (symptom history, skin prick tests, specific IgE assay, respiratory function tests) at age seven. Results: Of the 68/222 (30.6%) children assessed at age seven, 15 (22.05%) presented with asthma and were mainly males (p = 0.033), 14 (20%) had respiratory allergies, 17 (25%) presented atopic dermatitis and none had a food allergy. Family history of atopy was associated with asthma and sensitisation to aeroallergens at age seven (p = 0.003, p = 0.007). Rhinovirus (hRV) infection and rhinovirus/respiratory syncytial virus (RSV) co-infection were significantly associated with asthma at age seven (p = 0.035, p = 0.04), but not with the initial severity of bronchiolitis. Eosinophil counts at ages three and seven were significantly higher in the asthmatics (p = 0.01, p = 0.046). Conclusion: Any infant, especially male, presenting a first episode of acute bronchiolitis due to hRV with a family history of atopy should be closely monitored via follow-up due to a higher risk for asthma at school age.
Published: 2021
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8. Physicochemical Stability of Monoclonal Antibodies: A Review

Author: Philip Chennell, Nicolas Tokhadzé, Valérie Sautou, Alain Astier, Yoann Le Basle, Institut de Chimie de Clermont-Ferrand (ICCF), SIGMA Clermont (SIGMA Clermont)-Institut de Chimie du CNRS (INC)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), CHU Clermont-Ferrand, Service Pharmacie [CHU Clermont-Ferrand], CHU Louise Michel [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], and CHU Clermont-Ferrand-CHU Louise Michel [Clermont-Ferrand]
Subjects: Chemical Phenomena, medicine.drug_class, Chemistry, Pharmaceutical, Stability (learning theory), Pharmaceutical Science, 02 engineering and technology, Monoclonal antibody, 030226 pharmacology & pharmacy, 03 medical and health sciences, Antineoplastic Agents, Immunological, 0302 clinical medicine, Protein structure, Drug Stability, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, medicine, Animals, Humans, ComputingMilieux_MISCELLANEOUS, Light exposure, Biological Products, Protein Stability, Chemistry, Study methodology, Antibodies, Monoclonal, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, 021001 nanoscience & nanotechnology, Protein tertiary structure, [SDV.SP.PG]Life Sciences [q-bio]/Pharmaceutical sciences/Galenic pharmacology, Biopharmaceutical, Biochemistry, Chemical stability, Stress, Mechanical, 0210 nano-technology
Abstract: Monoclonal antibodies (mAbs) are subject to instability issues linked to their protein nature. In this work, we review the different mechanisms that can be linked to monoclonal antibodies instability, the parameters, and conditions affecting their stability (protein structure and concentration, temperature, interfaces, light exposure, excipients and contaminants, and agitation) and the different analytical methods used for appropriate physicochemical stability studies: physical stability assays (aggregation, fragmentation, and primary, secondary, and tertiary structure analysis), chemical stability assays and quantitative assays. Finally, data from different published stability studies of mAbs formulations, either in their reconstituted form, or in diluted ready to administer solutions, was compiled. Overall, the physicochemical stability of mAbs is linked to numerous factors such as formulation, environment, and manipulations, and must be thoroughly investigated using several complementary analytical techniques, each of which allowing specific characterization information to be harvested. Several stability studies have been published, some of them showing possibilities of extended stability. However, those data should be questioned due to potential lacks in study methodology.
Published: 2020
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9. Transcriptional alterations in glioma result primarily from DNA methylation–independent mechanisms

Author: Mélanie Müller-Barthélémy, Elisa Le Boiteux, Franck Court, Julian Biau, Lucie Karayan-Tapon, Toufic Khalil, Pierre Verrelle, Philippe Arnaud, Jean-Louis Kemeny, Anne Fogli, Catherine Vaurs-Barrière, Bruno Pereira, Emmanuel Chautard, Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Service de Biochimie et Génétique Moléculaire [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Thérapie ciblée combinatoire en Onco-Hématologie (EA3846), Université d'Auvergne - Clermont-Ferrand I (UdA), Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Laboratoire de pathologie, Service de Neurochirurgie [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], Institut National de la Transfusion Sanguine [Paris] (INTS), Arnaud, Philippe, Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Service de Biochimie Médicale et Biologie Moléculaire [CHU Clermont-Ferrand], Centre Jean Perrin, CRLCC Jean Perrin, Unité de biostatistiques, CHU Clermont-Ferrand-Hôpital Montpied, Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), CHU Clermont-Ferrand-Hôpital Gabriel Montpied, Service de Neurochirurgie [CHU Clermont-Ferrand], ANR-16-IDEX-0001,CAP 20-25,CAP 20-25(2016), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], and Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, Jumonji Domain-Containing Histone Demethylases, Transcription, Genetic, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease_cause, Epigenesis, Genetic, Histones, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Genetics, medicine, Humans, transcriptional defects, Epigenetics, Promoter Regions, Genetic, Gene, ComputingMilieux_MISCELLANEOUS, Genetics (clinical), 030304 developmental biology, 0303 health sciences, Mutation, Research, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], Promoter, Glioma, DNA Methylation, Chromatin, Isocitrate Dehydrogenase, 3. Good health, Cell biology, Gene Expression Regulation, Neoplastic, [SDV.BBM.MN] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], CpG site, CpG-island, Cancer cell, DNA methylation, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], CpG Islands, Female, 030217 neurology & neurosurgery, Bivalent chromatin
Abstract: In cancer cells, aberrant DNA methylation is commonly associated with transcriptional alterations, including silencing of tumor suppressor genes. However, multiple epigenetic mechanisms, including polycomb repressive marks, contribute to gene deregulation in cancer. To dissect the relative contribution of DNA methylation–dependent and –independent mechanisms to transcriptional alterations at CpG island/promoter-associated genes in cancer, we studied 70 samples of adult glioma, a widespread type of brain tumor, classified according to their isocitrate dehydrogenase (IDH1) mutation status. We found that most transcriptional alterations in tumor samples were DNA methylation–independent. Instead, altered histone H3 trimethylation at lysine 27 (H3K27me3) was the predominant molecular defect at deregulated genes. Our results also suggest that the presence of a bivalent chromatin signature at CpG island promoters in stem cells predisposes not only to hypermethylation, as widely documented, but more generally to all types of transcriptional alterations in transformed cells. In addition, the gene expression strength in healthy brain cells influences the choice between DNA methylation- and H3K27me3-associated silencing in glioma. Highly expressed genes were more likely to be repressed by H3K27me3 than by DNA methylation. Our findings support a model in which altered H3K27me3 dynamics, more specifically defects in the interplay between polycomb protein complexes and the brain-specific transcriptional machinery, is the main cause of transcriptional alteration in glioma cells. Our study provides the first comprehensive description of epigenetic changes in glioma and their relative contribution to transcriptional changes. It may be useful for the design of drugs targeting cancer-related epigenetic defects.
Published: 2019
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10. 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
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11. Walking Speed Is Correlated With the Isokinetic Muscular Strength of the Knee in Patients With Charcot-Marie-Tooth Type 1A

Author: Pierre Clavelou, Vivien Reynaud, Frederic Taithe, Claire Morel, Emmanuel Coudeyre, Catherine Cornut-Chauvinc, Pascal Givron, Bruno Pereira, Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Clinique Charcot, Direction de la Recherche Clinique et de l'Innovation, Pole Recherche, Service de Neurologie [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Clermont-Ferrand University Hospital, CHU Gabriel Montpied [Clermont-Ferrand], and CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand]
Subjects: Adult, Male, musculoskeletal diseases, 030506 rehabilitation, medicine.medical_specialty, Knee Joint, Isokinetic Muscular Strength, [SDV]Life Sciences [q-bio], Physical Therapy, Sports Therapy and Rehabilitation, Walking, Concentric, Physical strength, Running, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Charcot-Marie-Tooth Disease, medicine, Eccentric, Humans, Orthopedics and Sports Medicine, In patient, Muscle Strength, 2. Zero hunger, 030222 orthopedics, Entire population, Knee extensors, business.industry, Rehabilitation, 030229 sport sciences, Middle Aged, Stride length, Gait Parameters, musculoskeletal system, Walking Speed, Preferred walking speed, Gait analysis, Isokinetic dynamometer, Female, Motor Deficit, 0305 other medical science, business, Cadence, Body mass index, human activities, 030217 neurology & neurosurgery
Abstract: Introduction/Background Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common hereditary neuropathy. Affected individuals have a distal motor deficit, initially affecting the lower limbs and impairing walking performance. Many studies have investigated this distal defect and the podo-orthotic compensations that may result. The use of an isokinetic dynamometer is relevant for objectively assessing the muscle strength of patients with neuromuscular disorders. No studies evaluated the incidence of muscle strength deficits of knee extensors and flexors on walking parameters for CMT1A patients. The purpose of this study is to find correlations between the isokinetic muscular strength (IMS) of the knee flexors (KF) and extensors (KE) and CMT1A patient walk parameters. Material and method IMS of the knee was evaluated at 3 angular velocities (120, 60°/s in concentric and 30°/s in eccentric) on an isokinetic dynamometer (Cybex®). The walk was evaluated by a gait analysis (GaitRite®). Results Thirty-three subjects were included (23 female, mean age 46.7 ± 13.3years, mean body mass index 25.7 ± 4.6 kg/m2). Mean scores for physical and mental health on the Medical Outcomes Study Short-Form 36 were 36.7 ± 9.0 and 47.9 ± 11.7. We found a correlation between the walking speed and the IMS of the KE for the entire population and between the walking speed and the IMS of the KE and KF for subjects under 50 years of age. Conclusion This study shows for the first time the correlation between the IMS of the knee and the walking speed. This highlights the value of the use of motion analysis devices for CMT1A patients.
Published: 2019
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12. Severe undernutrition increases bleeding risk on vitamin-K antagonists

Author: Christine Morand, Aurélien Lebreton, Damien Richard, Farès Moustafa, Aurélien Mulliez, Loic Dopeux, Frédéric Dutheil, Jeannot Schmidt, Yves Boirie, N. Farigon, E. Gentes, Dorian Teissandier, Pôle Urgences [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), Service de Nutrition Clinique [CHU Clermont-Ferrand], Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Service de Pharmacologie Médicale [CHU Clermont-Ferrand], Service d’Hématologie Biologique [CHU Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Centre de Ressources et Compétences des Maladies Hémorragiques Constitutionnelles [CHU Clermont-Ferrand] (CRC-MHC), CHU Estaing [Clermont-Ferrand], Australian Catholic University (ACU), Laboratoire de Psychologie Sociale et Cognitive (LAPSCO), and Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Male, medicine.medical_specialty, Vitamin K, medicine.drug_class, Micronutriment, 030209 endocrinology & metabolism, Hemorrhage, Vitamin k, Critical Care and Intensive Care Medicine, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Atrial Fibrillation, medicine, micronutrient, Humans, Prospective Studies, Prospective cohort study, Plasma zinc, Aged, 2. Zero hunger, Aged, 80 and over, 030109 nutrition & dietetics, Nutrition and Dietetics, business.industry, Malnutrition, Bleeding, Anticoagulants, Nutritional status, Undernutrition, Vitamin K antagonist, medicine.disease, Micronutrient, 3. Good health, Case-Control Studies, Female, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Major bleeding, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Anticoagulant agent
Abstract: Summary Introduction Hemorrhage occurs in 7–10% of patients treated with vitamin K antagonist (VKA), with major bleeding in 1–3%. Impact of nutritional status on the bleeding risk of patients on anticoagulants is still poorly documented. Our study aimed to analyze the link between the nutritional status of patients on VKA and the occurrence of hemorrhagic events. We also analyzed micronutrients status. Methods A case–control, monocentric, and prospective study was conducted from August 2012 to October 2015. The case patients were those presenting with major bleeding and control patients those without any bleeding under VKA treatment. Results Overall, 294 patients under VKA treatment were paired according to age, gender, and index normalized ratio (INR). Out of these, 98 (33.3%) had major bleeding and 196 (66.7%) did not have any bleeding. Additionally, more than two-thirds of patients displayed undernutrition, which was more prevalent in bleeding than non-bleeding patients (OR = 1.85, CI95%: 1.07–3.21). There was a higher bleeding risk for those with severe undernutrition (OR = 2.66, CI95%: 1.58–4.46), with no difference found concerning moderate undernutrition. Bleeding patients had lower plasma-zinc concentrations than non-bleeding patients (9.4 ± 3.6 vs. 10.5 ± 3.7 μmol/L, p = 0.003); among them, there was a higher rate of patients with plasma zinc under 5 μmol/L (9% vs. 2%, p Conclusion Patients with undernutrition on VKA exhibit a significantly higher bleeding risk, which increases three-fold in case of severe undernutrition. The evaluation of nutritional status provides additional, valuable prognosis information prior to initiating VKA therapy. ClinicalTrials.gov number NCT 01742871.
Published: 2021
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13. Effects of Totum-63 on glucose homeostasis and post-prandial glycemia: a translational study

Author: Christophe Montaurier, Gisèle Pickering, Yolanda F. Otero, Geoffroy Marceau, Florian Le Joubioux, Gilles Ducheix, M. Bargetto, Pascal Sirvent, Vincent Sapin, Aurore Vluggens, Claude Dubray, Doriane Ripoche, Bruno Guigas, Murielle Cazaubiel, Sylvia Boulliau, Nathalie Boisseau, Vivien Chavanelle, Nicolas Macian, Sébastien Peltier, Thierry Maugard, Frédéric Dutheil, Christian Dualé, Valbiotis R & D [Riom], Valbiotis R&D [Perigny], Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), CIC Clermont Ferrand, Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-Centre de Pharmacologie Clinique, Service de Biochimie et Génétique Moléculaire [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Laboratoire de Psychologie Sociale et Cognitive (LAPSCO), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Leiden University Medical Center (LUMC), LIttoral ENvironnement et Sociétés - UMRi 7266 (LIENSs), Université de La Rochelle (ULR)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques (AME2P), Université Clermont Auvergne (UCA)-UFR Sciences et Techniques des Activités Physiques et Sportives - Clermont-Auvergne (UFR STAPS - UCA), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), MMPC/DiaComp [DK076169], [DK115255], Valbiotis SAS, Partenaires INRAE-Partenaires INRAE, CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], Universiteit Leiden, LIttoral ENvironnement et Sociétés (LIENSs), and La Rochelle Université (ULR)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Blood Glucose, Male, Physiology, Chrysanthemum, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Vaccinium myrtillus, Pilot Projects, Type 2 diabetes, Translational Research, Biomedical, Mice, 0302 clinical medicine, prevention, Cynara scolymus, Glucose homeostasis, Homeostasis, glucose, 2. Zero hunger, biology, diabetes, translational, Middle Aged, Postprandial Period, Postprandial, 030220 oncology & carcinogenesis, Piper nigrum, Research Article, Adult, medicine.medical_specialty, Glycemic Control, 03 medical and health sciences, Physiology (medical), Internal medicine, Diabetes mellitus, Olea, medicine, Animals, Humans, business.industry, Plant Extracts, Insulin, nutritional and metabolic diseases, Overweight, medicine.disease, Mice, Inbred C57BL, Insulin receptor, 030104 developmental biology, Endocrinology, Hyperglycemia, biology.protein, Lean body mass, Steatosis, business
Abstract: International audience; Global prevalence of type 2 diabetes (T2D) is rising and may affect 700 million people by 2045. Totum-63 is a polyphenol-rich natural composition developed to reduce the risk of T2D. We first investigated the effects of Totum-63 supplementation in highfat diet (HFD)-fed mice for up to 16 wk and thereafter assessed its safety and efficacy (2.5 g or 5 g per day) in 14 overweight men [mean age 51.5 yr, body mass index (BMI) 27.6 kg.m(-2)] for 4 wk. In HFD-fed mice, Totum-63 reduced body weight and fat mass gain, whereas lean mass was unchanged. Moreover, fecal energy excretion was higher in Totum-63-supplemented mice, suggesting a reduction of calorie absorption in the digestive tract. In the gut, metagenomic analyses of fecal microbiota revealed a partial restoration of HFD-induced microbial imbalance, as shown by principal coordinate analysis of microbiota composition. HFD-induced increase in HOMA-IR score was delayed in supplemented mice, and insulin response to an oral glucose tolerance test was significantly reduced, suggesting that Totum-63 may prevent HFD-related impairments in glucose homeostasis. Interestingly, these improvements could be linked to restored insulin signaling in subcutaneous adipose tissue and soleus muscle. In the liver, HFD-induced steatosis was reduced by 40% (as shown by triglyceride content). In the subsequent study in men, Totum-63 (5g.day-1) improved glucose and insulin responses to a high-carbohydrate breakfast test (84% kcal carbohydrates). It was well tolerated, with no clinically significant adverse events reported. Collectively, these data suggest that Totum-63 could improve glucose homeostasis in both HFD-fed mice and overweight individuals, presumably through a multitargeted action on different metabolic organs.NEW & NOTEWORTHY Totum-63 is a novel polyphenol-rich natural composition developed to reduce the risk of T2D. Totum-63 showed beneficial effects on glucose homeostasis in HFD-fed mice, presumably through a multitargeted action on different metabolic organs. Totum-63 was well tolerated in humans and improved postprandial glucose and insulin responses to a high-carbohydrate breakfast test.
Published: 2021
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14. A chronic low-dose magnesium L-lactate administration has a beneficial effect on the myocardium and the skeletal muscles

Author: Isabelle Hininger-Favier, Chrystèle Jouve, Damien Bouvier, Jean-Paul Rigaudière, Véronique Patrac, Stéphane Walrand, Luc Demaison, Hervé Dubouchaud, Marlène Magalhaes Pinto, Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), 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), Service de Biochimie et Génétique Moléculaire [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, French National Institute of Agronomical Research (INRAE), CHU Estaing [Clermont-Ferrand], and CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand]
Subjects: Cardiac function curve, Male, medicine.medical_specialty, Physiology, [SDV]Life Sciences [q-bio], chemistry.chemical_element, Skeletal muscle, Calcium, medicine.disease_cause, Biochemistry, Calcium in biology, Contractility, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Animals, Magnesium, Rats, Wistar, Muscle, Skeletal, 030304 developmental biology, Acidosis, 2. Zero hunger, 0303 health sciences, Myocardium, Sodium, Water, Heart, General Medicine, L-lactate, 3. Good health, Rats, Diet, medicine.anatomical_structure, Endocrinology, chemistry, Lactates, medicine.symptom, Calcium-Calmodulin-Dependent Protein Kinase Type 2, 030217 neurology & neurosurgery, Oxidative stress
Abstract: International audience; The purpose of this study was to determine whether magnesium L-lactate is responsible for having a beneficial effect on the myocardium and the skeletal muscles and how this substrate acts at the molecular level. Twenty seven young male Wistar rats were supplied with a magnesium L-lactate (L) solution, a magnesium chloride (M) solution and/or water (W) as a vehicle for 10 weeks. The treated animals absorbed the L and M solutions as they wished since they also had free access to water. After 9 weeks of treatment, in vivo cardiac function was determined ultrasonically. The animals were sacrificed at the end of the tenth week of treatment and the heart was perfused according to the Langendorff method by using a technique allowing the determination of cardiomyocyte activity (same coronary flow in the two groups). Blood was collected and skeletal muscles of the hind legs were weighed. The myocardial expressions of the sodium/proton exchange 1 (NHE1) and sodium/calcium exchange 1 (NCX1), intracellular calcium accumulation, myocardial magnesium content, as well as systemic and tissue oxidative stress, were determined. Animals of the L group absorbed systematically a low dose of L-lactate (31.5 ± 4.3 µg/100 g of body weight/day) which was approximately four times higher than that ingested in the W group through the diet supplied. Ex vivo cardiomyocyte contractility and the mass of some skeletal muscles (tibialis anterior) were increased by the L treatment. Myocardial calcium was decreased, as was evidenced by an increase in total CaMKII expression, without any change in the ratio between phosphorylated CaMKII and total CaMKII. Cardiac magnesium tended to be elevated. Our results suggest that the increased intracellular magnesium concentration was related to L-lactate-induced cytosolic acidosis and to the activation of the NHE1/NCX1 axis. Interestingly, systemic oxidative stress was reduced by the L treatment whereas the lipid profile of the animals was unaltered. Taken together, these results suggest that a chronic low-dose L-lactate intake has a beneficial health effect on some skeletal muscles and the myocardium through the activation of the NHE1/NCX1 axis, a decrease in cellular calcium and an increase in cellular magnesium. The treatment can be beneficial for the health of young rodents in relation to chronic oxidative stress-related diseases.
Published: 2021
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15. Hémorragie intracérébrale fatale chez un patient atteint d'une leucémie chronique à polynucléaires neutrophiles : à propos d'un cas et revue de la littérature

Author: Mathilde Hunault Berger, A.-F. Sapin, Thomas Sinegre, A. Lebreton, L. Talon, B. de Renzis, Laurence Sanhes, M. Fiore, Service d’Hématologie Biologique [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre de Ressources et Compétences des Maladies Hémorragiques Constitutionnelles [CHU Clermont-Ferrand] (CRC-MHC), CHU Estaing [Clermont-Ferrand], and CHU Clermont-Ferrand-CHU Clermont-Ferrand
Subjects: 0301 basic medicine, Gynecology, medicine.medical_specialty, business.industry, [SDV]Life Sciences [q-bio], Gastroenterology, 3. Good health, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal Medicine, medicine, business
Abstract: Resume Introduction La leucemie chronique a neutrophiles (LCN) est un syndrome myeloproliferatif rare caracterise par une production importante de polynucleaires neutrophiles matures. L'une des complications les plus severes est la survenue d'evenements hemorragiques, pouvant parfois conduire au deces des patients. Observation Nous rapportons une observation de LCN affectant un homme de 75 ans. L'observation clinique detaillait de multiples complications hemorragiques. Les explorations biologiques objectivaient des anomalies de l'agregation plaquettaire et une elevation de l'elastase leucocytaire circulante. L'evolution avait ete marquee par une hemorragie intracerebrale conduisant au deces du patient 7 mois apres le diagnostic. Conclusion Cette tendance hemorragique a ete rapportee a plusieurs reprises dans des cas de LCN. Cependant, les mecanismes physiopathologiques a l'origine des saignements ne sont pas encore completement elucides.
Published: 2020
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16. Do Ophthalmic Solutions of Amphotericin B Solubilised in 2-Hydroxypropyl-γ-Cyclodextrins Possess an Extended Physicochemical Stability?

Author: Philip Chennell, Mouloud Yessaad, Florence Abd El Kader, Mireille Jouannet, Mathieu Wasiak, Yassine Bouattour, Valérie Sautou, Institut de Chimie de Clermont-Ferrand (ICCF), Institut de Chimie du CNRS (INC)-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), Service Pharmacie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Louise Michel [Clermont-Ferrand], CHU Clermont-Ferrand, CHU Louise Michel [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], and CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand]
Subjects: lcsh:Pharmacy and materia medica, [SDV]Life Sciences [q-bio], fungal keratitis, lcsh:RS1-441, stability, γ-cyclodextrins, Article, amphotericin B
Abstract: Fungal keratitis is a sight-threatening disease for which amphotericin B eye drops is one of the front-line treatments. Unfortunately, there are currently no commercial forms available, and there is little data concerning the long-term stability of compounded formulations based on intravenous dosages forms. New formulations of amphotericin B ophthalmic solutions solubilised with &gamma, cyclodextrins have shown promising in-vitro results, but stability data is also lacking. The objective of this study was therefore to investigate the stability of a formulation of ready-to-use amphotericin B solubilised in 2-hydroxypropyl-&gamma, cyclodextrins (AB-HP-&gamma, CD), for 350 days. An amphotericin B deoxycholate (ABDC) formulation was used as a comparator. Analyses used were the following: visual inspection, turbidity, osmolality and pH measurements, amphotericin B quantification by a stability-indicating liquid chromatography method, breakdown product research, and sterility assay. AB-HP-&gamma, CD formulation showed signs of chemical instability (loss of amphotericin B) after 28 and 56 days at 25 &deg, C and 5 &deg, C. Adding an antioxidant (ascorbic acid) to the formulation did not improve stability. ABDC formulation showed signs of physical instability (increased turbidy and amphotericin B precipitation) after 28 days and 168 days at 25 &deg, C. As such, AB-HP-&gamma, CD formulation does not provide long-term stability for ophthalmic amphotericin B solutions.
Published: 2020
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17. Stability of Ophthalmic Atropine Solutions for Child Myopia Control

Author: Baptiste Berton, Mathieu Wasiak, Valérie Sautou, Mireille Jouannet, Philip Chennell, Mouloud Yessaad, Yassine Bouattour, Service Pharmacie [CHU Clermont-Ferrand], CHU Louise Michel [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Institut de Chimie de Clermont-Ferrand (ICCF), Institut de Chimie du CNRS (INC)-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), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], and CHU Clermont-Ferrand-CHU Louise Michel [Clermont-Ferrand]
Subjects: Preservative, [SDV]Life Sciences [q-bio], atropine, lcsh:RS1-441, Pharmaceutical Science, Ph measurement, 030226 pharmacology & pharmacy, Article, lcsh:Pharmacy and materia medica, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, medicine, myopia, [SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials, Chromatography, Chemistry, [CHIM.MATE]Chemical Sciences/Material chemistry, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, stability, Tropic acid, 3. Good health, Atropine, Low-density polyethylene, [CHIM.POLY]Chemical Sciences/Polymers, [SDV.SP.PG]Life Sciences [q-bio]/Pharmaceutical sciences/Galenic pharmacology, Compounding, 030221 ophthalmology & optometry, ophthalmic solution, medicine.drug
Abstract: Myopia is an ophthalmic condition affecting more than 1/5th of the world population, especially children. Low-dose atropine eyedrops have been shown to limit myopia evolution during treatment. However, there are currently no commercial industrial forms available and there is little data published concerning the stability of medications prepared by compounding pharmacies. The objective of this study was to evaluate the stability of two 0.1 mg/mL atropine formulations (with and without antimicrobiobial preservatives) for 6 months in two different low-density polyethylene (LDPE) multidose eyedroppers. Analyses used were the following: visual inspection, turbidity, chromaticity measurements, osmolality and pH measurements, atropine quantification by a stability-indicating liquid chromatography method, breakdown product research, and sterility assay. In an in-use study, atropine quantification was also performed on the drops emitted from the multidose eyedroppers. All tested parameters remained stable during the 6 months period, with atropine concentrations above 94.7% of initial concentration. A breakdown product (tropic acid) did increase slowly over time but remained well below usually admitted concentrations. Atropine concentrations remained stable during the in-use study. Both formulations of 0.1 mg/mL of atropine (with and without antimicrobial preservative) were proved to be physicochemically stable for 6 months at 25 &deg, C when stored in LDPE bottles, with an identical microbial shelf-life.
Published: 2020
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18. Human Amnion Epithelial Cells (AECs) Respond to the FSL-1 Lipopeptide by Engaging the NLRP7 Inflammasome

Author: Marilyne Lavergne, Corinne Belville, Héléna Choltus, Christelle Gross, Régine Minet-Quinard, Denis Gallot, Vincent Sapin, Loïc Blanchon, Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Service de Biochimie et Génétique Moléculaire [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Service de Gynécologie [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Génétique, Reproduction et Développement (GReD ), BLANCHON, LOIC, Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])
Subjects: 0301 basic medicine, Mycoplasma salivarium, ved/biology.organism_classification_rank.species, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Pyrin domain, 0302 clinical medicine, fetal membranes, Pregnancy, amnion epithelial cells, Immunology and Allergy, Receptor, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, Original Research, Mycoplasma fermentans, biology, Amnion, Chemistry, Caspase 1, Inflammasome, Blot, medicine.anatomical_structure, Host-Pathogen Interactions, Female, Pregnancy Trimesters, Oligopeptides, medicine.drug, Signal Transduction, lcsh:Immunologic diseases. Allergy, Immunology, mycoplasmas, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, NLRP7, Diglycerides, 03 medical and health sciences, medicine, Humans, inflammasomes, Adaptor Proteins, Signal Transducing, ved/biology, Cesarean Section, Parturition, Epithelial Cells, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, biology.organism_classification, Molecular biology, CARD Signaling Adaptor Proteins, [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, 030104 developmental biology, inflammation, FSL-1, CARD domain, lcsh:RC581-607, 030215 immunology
Abstract: Context and Objectives: Inflammation is the leading mechanism involved in both physiological and pathological rupture of fetal membranes. Our aim was to obtain a better characterization of the inflammasome-dependent inflammation processes in these tissues, with a particular focus on the nucleotide-binding oligomerization domain (NOD)-like receptor, pyrin domain containing protein 7 (NLRP7) inflammasome. Methods: The presence of NLRP7 inflammasome actors [NLRP7, apoptosis-associated speck-like protein containing a CARD domain (ASC), and caspase-1] was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) in human amnion and choriodecidua at the three trimesters and at term. The protein concentrations were then determined by enzyme-linked immunosorbent assay in term tissues, with or without labor. The presence of Mycoplasma salivarium and Mycoplasma fermentans in human fetal membranes was investigated using a PCR approach. Human amnion epithelial cells (AECs) were treated for 4 or 20 h with fibroblast-stimulating lipopeptide-1 (FSL-1), a M. salivarium-derived ligand. Transcripts and proteins quantity was then measured by RT-quantitative PCR and Western blotting, respectively. NLRP7 and ASC colocalization was confirmed by immunofluorescence. Western blots allowed analysis of pro-caspase-1 and gasdermin D cleavage. Results: NLRP7, ASC, and caspase-1 transcripts were expressed in both sheets of human fetal membranes during all pregnancy stages, but only ASC protein expression was increased with labor. In addition, M. salivarium and M. fermentans were detected for the first time in human fetal membranes. NLRP7 and caspase-1 transcripts, as well as NLRP7, ASC, and pro-caspase-1 protein levels, were increased in FSL-1-treated AECs. The NLRP7 inflammasome assembled around the nucleus, and pro-caspase-1 and gasdermin D were cleaved into their mature forms after FSL-1 stimulation. Conclusion: Two new mycoplasmas, M. salivarium and M. fermentans, were identified in human fetal membranes, and a lipopeptide derived from M. salivarium was found to induce NLRP7 inflammasome formation in AECs.
Published: 2020
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19. Occurrence of a RAGE-Mediated Inflammatory Response in Human Fetal Membranes

Author: Héléna Choltus, Marilyne Lavergne, Corinne Belville, Denis Gallot, Régine Minet-Quinard, Julie Durif, Loïc Blanchon, Vincent Sapin, Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Service de Biochimie et Génétique Moléculaire [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, BLANCHON, LOIC, Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Estaing [Clermont-Ferrand], and CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand]
Subjects: 0301 basic medicine, endocrine system diseases, Physiology, medicine.medical_treatment, Inflammation, Context (language use), Biology, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, HMGB1, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, lcsh:Physiology, RAGE (receptor), 03 medical and health sciences, 0302 clinical medicine, fetal membranes, Physiology (medical), medicine, rupture of fetal membranes, Receptor, Original Research, 030219 obstetrics & reproductive medicine, Amnion, lcsh:QP1-981, alarmins, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, RAGE, 3. Good health, Cell biology, [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, 030104 developmental biology, Cytokine, medicine.anatomical_structure, sterile inflammation, embryonic structures, biology.protein, Cytokine secretion, medicine.symptom
Abstract: International audience; Context: Sterile inflammation has been shown to play a key role in the rupture of the fetal membranes (FMs). Moreover, an early and exacerbated runaway inflammation can evolve into a preterm premature rupture of membranes and lead to potential preterm birth. In this context, we investigated the receptor for advanced glycation end products (RAGE), an axis implied in physiological sterile inflammation, in conjunction with two major ligands: AGEs and High-Mobility Group Box 1 (HMGB1). Our first objective was to determine the spatiotemporal expression profiles of the different actors of the RAGE-signaling axis in human FMs, including its intracellular adaptors Diaphanous-1 and Myd88. Our second goal was to evaluate the functionality of RAGE signaling in terms of FMs inflammation. Methods The presence of the actors (RAGE, HMGB1, Myd88, and Diaphanous-1) at the mRNA level was investigated by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in the human amnion and choriodecidua at the three trimesters and at term. Measurements were conducted at two distinct zones: the zone of intact morphology (ZIM) and the zone of altered morphology (ZAM). Then, proteins were quantified using Western blot analysis, and their localization was evaluated by immunofluorescence in term tissues. In addition, pro-inflammatory cytokine secretion was quantified using a Multiplex assay after the treatment of amnion and choriodecidua explants with two RAGE ligands (AGEs and HMGB1) in the absence or presence of a RAGE inhibitor (SAGEs). Results The FMs expressed the RAGE-signaling actors throughout pregnancy. At term, RNA and protein overexpression of the RAGE, HMGB1, and Diaphanous-1 were found in the amnion when compared to the choriodecidua, and the RAGE was overexpressed in the ZAM when compared to the ZIM. The two RAGE ligands (AGEs and HMGB1) induced differential cytokine production (IL1β and TNFα) in the amnion and choriodecidua. Conclusion Considered together, these results indicate that RAGE signaling is present and functional in human FMs. Our work opens the way to a better understanding of FMs weakening dependent on a RAGE-based sterile inflammation.
Published: 2020
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20. Study of sRAGE, HMGB1, AGE, and S100A8/A9 Concentrations in Plasma and in Serum-Extracted Extracellular Vesicles of Pregnant Women With Preterm Premature Rupture of Membranes

Author: Damien Bouvier, Yves Giguère, Loïc Blanchon, Emmanuel Bujold, Bruno Pereira, Nathalie Bernard, Denis Gallot, Vincent Sapin, Jean-Claude Forest, Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Biochimie et Génétique Moléculaire [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Centre de recherche du CHU de Québec-Université Laval (CRCHUQ), CHU de Québec–Université Laval, Université Laval [Québec] (ULaval)-Université Laval [Québec] (ULaval), Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], and BLANCHON, LOIC
Subjects: 0301 basic medicine, preterm premature rupture of membranes, Physiology, Inflammation, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, high-mobility group box 1, lcsh:Physiology, [SDV.BDLR.RS]Life Sciences [q-bio]/Reproductive Biology/Sexual reproduction, Andrology, 03 medical and health sciences, 0302 clinical medicine, Fetal membrane, Physiology (medical), medicine, S100A8/A9, soluble receptor for advanced glycation end products, Original Research, Pregnancy, Fetus, [SDV.BDLR.RS] Life Sciences [q-bio]/Reproductive Biology/Sexual reproduction, 030219 obstetrics & reproductive medicine, lcsh:QP1-981, business.industry, advanced glycation end products, Extracellular vesicle, medicine.disease, Pathophysiology, 3. Good health, [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, 030104 developmental biology, Gestation, medicine.symptom, business, extracellular vesicles, Premature rupture of membranes
Abstract: International audience; Preterm premature rupture of membranes (PPROM), defined as rupture of fetal membranes prior to 37 weeks of gestation, complicates approximately 2–4% of pregnancies and is responsible for 40% of all spontaneous preterm births. PPROM arises from complex pathophysiological pathways with a key actor: inflammation. Sterile inflammation is a feature of senescence-associated fetal membrane maturity. During specific steps of sterile inflammation, cells also release highly inflammatory damage-associated molecular pattern markers (DAMPs), such as high-mobility group box 1 (HMGB1) or S100A8/A9, known to link and activate the receptor for advanced glycation end products (RAGE). The objective of this study was to measure longitudinally during pregnancy concentrations of the soluble form of RAGE (sRAGE) and its main ligands (AGE, HMGB1, S100A8/A9) in blood specimens. We studied 246 pregnant women (82 with PPROM and 164 matched control pregnant women without complications) from a cohort of 7,866 pregnant women recruited in the first trimester and followed during pregnancy until delivery. sRAGE, AGE, HMGB1, and S100A8/A9 concentrations were measured in plasma and in serum-extracted extracellular vesicles from first trimester (T1), second trimester (T2), and delivery (D). In plasma, we observed, in both PPROM and control groups, (i) a significant increase of HMGB1 concentrations between T1 vs. T2, T1 vs. D, but not between T2 vs. D; (ii) a significant decrease of sRAGE concentrations between T1 and T2 and a significant increase between T2 and D; (iii) a significant decrease of AGE from T1 to D; (iv) no significant variation of S100A8/A9 between trimesters. In intergroup comparisons (PPROM vs. control group), there were no significant differences in time variation taking into account the matching effects. There was a correlation between plasma and serum-extracted extracellular vesicle concentrations of sRAGE, AGE, HMGB1, and S100A8/A9. Our results suggest that the rupture of fetal membranes (physiological or premature) is accompanied by a variation in plasma concentrations of sRAGE, HMGB1, and AGE. The study of RAGE and its main ligands in extracellular vesicles did not give additional insight into the pathophysiological process conducting to PPROM.
Published: 2020
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21. Aplastic anemia in the elderly: a nationwide survey on behalf of the French Reference Center for Aplastic Anemia

Author: Lucile Bussot, Anne Banos, Matthieu Resche-Rigon, Delphine Lebon, Fiorenza Barraco, Didier Bouscary, Jerome Tamburini, Natacha Maillard, Fabrice Jardin, Laurence Simon, Flore Sicre de Fontbrune, Ambroise Marçais, Adrien Contejean, Jean-Yves Cahn, Pierre Hirsch, Lionel Adès, Louis Terriou, Régis Peffault de Latour, Gérard Socié, Marion Alcantara, Etienne Lengliné, Luc Mathieu Fornecker, Cécile Moluçon-Chabrot, Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) (SBIM), 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)-Institut national du cancer [Boulogne] (INCA)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Groupe d'étude des proliférations lymphoïdes (GPL), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), CIC - Biotherapie - GHU Ouest APHP (CIC-BT 502), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Université de Paris (UP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], University Paris Descartes Sorbonne Paris Cité, Imagine Institute, Paris, CHU Amiens-Picardie, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Hôpital Claude Huriez [Lille], CHU Lille, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Hôpital de Bayonne, CH de la Côte Basque, Centre Hospitalier Universitaire [Grenoble] (CHU), 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), Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Strasbourg, service hématologie Strasbourg, Service d’Hématologie Biologique [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], Département d'Oncologie et Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), 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), DESSAIVRE, Louise, Université Paris Descartes - Paris 5 (UPD5), Université Sorbonne Paris Cité (USPC), CHU Necker - Enfants Malades [AP-HP], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Université Paris Diderot - Paris 7 (UPD7), Le CHCB, Centre Hospitalier de la Côte Basque, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Ecotaxie, microenvironnement et développement lymphocytaire (EMily (UMR_S_1160 / U1160)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and CHU Grenoble
Subjects: Pediatrics, medicine.medical_specialty, Population ageing, Palliative care, Anemia, [SDV]Life Sciences [q-bio], Immunology, Eltrombopag, Disease, 030204 cardiovascular system & hematology, Biochemistry, Article, chemistry.chemical_compound, 03 medical and health sciences, 0302 clinical medicine, Median follow-up, Surveys and Questionnaires, Severity of illness, medicine, Humans, Aplastic anemia, Aged, Antilymphocyte Serum, Performance status, business.industry, Bone marrow failure, Anemia, Aplastic, Standard of Care, Cell Biology, Hematology, medicine.disease, Bone Marrow Failure, 3. Good health, [SDV] Life Sciences [q-bio], Regimen, chemistry, 030220 oncology & carcinogenesis, Cyclosporine, business, Immunosuppressive Agents, 030215 immunology
Abstract: Introduction Aplastic anemia (AA) is a rare but potentially life-threatening disease that frequently occurs in older patients. Various therapeutic options can be proposed and data regarding the ideal first line treatment of AA in this ageing population remains scarce. Methods We conducted a retrospective nationwide multicenter study in France to examine current treatments for AA patients over 60 years old within a 10-year period (1/1/2007 to 12/31/2016). Our aims were to evaluate efficacy and tolerance of AA treatment, and to analyze predictive factors for response and survival. Patients who were diagnosed with AA by a bone marrow biopsy at the age of 60 or over were included in the study. Results Over the course of a decade, 88 patients (median age 68.5) were identified in 19 centers, with a median follow-up of 32.1 months; 49% were women, the median Charlson comorbidity index was 2 (range 0-6), the median performance status was 1 (range 0-3), 21% had very severe (vSAA) and 36% severe AA. We analyzed 184 treatment lines which comprised ATG-CsA (33%, including 72% with horse ATG), CsA alone (14%), androgen alone (14%), eltrombopag alone (10%), CsA associated with androgen or eltrombopag (9%), and other treatments (20%). First-line treatment was ATG-CsA for half of patients. Comparisons of patients treated in first line with ATG-CsA, CsA or other treatments revealed that patients receiving ATG-CsA were significantly younger (66 years, vs. 71.5 vs. 71.5, respectively, p=0.007), more frequently female (61%, vs. 50% vs. 27%, p=0.02) and had a lower platelet count (8x109/L, vs. 12x109/L vs. 15x109/L, p=0.025). We found no difference with respect to weight, Charlson comorbidity index score, performance status or disease severity between first line treatment regimens. After first-line therapy, 32% of patients achieved a complete response (CR), and 15% a partial response (PR). After the 181 assessable treatment lines, 19% achieved CR and 19% a PR. Median time until best response was 151 days. The overall response rate (ORR) was 62% with ATG-CsA (70% as a first-line treatment), 35% with CsA alone (39% as first-line), 22% with eltrombopag, and 21% with androgen. The ORR in patients over 70 years receiving ATG-CsA (n=16) was 81% (50% achieving a CR). Responses were significantly better in first line and in patients with good performance status, as well as in those that had received ATG-CsA (ORR of 70% after first-line treatment). In a multivariable analysis using ATG-CsA as a baseline, we found that CsA alone (OR 0.35 (0.13;0.96), p=0.042), eltrombopag (OR 0.12 (0.03;0.54), p=0.0057) and androgens (OR 0.17 (0.05;0.58), p=0.0047) were all individually associated with lower response rates. The main complications were infections (grade III/IV, 35% of treatment lines including 9 deaths (5%)), and renal issues (grade-III/IV, 29%). ATG-CsA was associated with significantly more infectious complications (72% vs. 24%, p Conclusion Our study showed a significantly better ORR with ATG-CsA than other regimens for treatment of AA in elderly, with more complications but no more death. Age per se is not a limiting factor for treatment with ATG-CsA: this regimen should be used as first-line treatment in elderly patients if they have a good performance status and low comorbidity index score. Among patients with adverse performance status or comorbidities contra-indicating the use of ATG, CsA alone or in combination may be safely used. Other strategies might be reserved for later courses of treatments. Supportive care may have a great impact on survival in this population. Disclosures Ades: JAZZ: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees; silent pharma: Consultancy; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Peffault De Latour:Pfizer Inc.: Consultancy, Honoraria, Research Funding; Amgen Inc.: Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Research Funding.
Published: 2019
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22. FGF14 ‐related episodic ataxia: delineating the phenotype of Episodic Ataxia type 9

Author: Jessica Hadjadj, Florence Riant, Franck Rejou, Ganaelle Remerand, Véronique Humbertclaude, Pierre Meyer, Julie Piarroux, Lucile Pinson, Christine Coubes, Agathe Roubertie, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Lariboisière, Université Paris Diderot - Paris 7 (UPD7)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 2Service de Génétique Moléculaire Neurovasculaire, Groupe hospitalier Saint-Louis - Lariboisière - Fernand Widal AP-HP, Paris, France, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service de Néonatologie [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service de Génétique Clinique, Département de génétique médicale, maladies rares et médecine personnalisée [CHRU Montpellier], Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], 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)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences de Montpellier (INM), MORNET, Dominique, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Service de néonatologie, CHU Estaing, Clermont-Ferrand, France, Département de génétique médicale, maladies rares et médecine personnalisée [CHRU de Montpellier], and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: 0301 basic medicine, Adult, Male, Pediatrics, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, [SDV]Life Sciences [q-bio], Neurosciences. Biological psychiatry. Neuropsychiatry, Nystagmus, Brief Communication, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, RC346-429, Child, Episodic ataxia, business.industry, General Neuroscience, Postural tremor, Middle Aged, medicine.disease, Phenotype, Pedigree, Fibroblast Growth Factors, [SDV] Life Sciences [q-bio], 030104 developmental biology, Child, Preschool, Ataxia, Female, Neurology. Diseases of the nervous system, Neurology (clinical), medicine.symptom, business, Brief Communications, 030217 neurology & neurosurgery, RC321-571
Abstract: International audience; We report four patients from two families who presented attacks of childhood-onset episodic ataxia associated with pathogenic mutations in the FGF14 gene. Attacks were triggered by fever, lasted several days, and had variable frequencies. Nystagmus and/or postural tremor and/or learning disabilities were noticed in individuals harboring FGF14 mutation with or without episodic ataxia. These cases and literature data delineate the FGF14-mutation-related episodic ataxia phenotype: wide range of age at onset (from childhood to adulthood), variable durations and frequencies, triggering factors including fever, and association to chronic symptoms. We propose to add FGF14-related episodic ataxia to the list of primary episodic ataxia as Episodic Ataxia type 9.
Published: 2020
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23. Serum soluble receptor for advanced glycation end-products during acute bronchiolitis in infant: Prospective study in 93 cases

Author: Karen Coste, Emmanuelle Rochette, Aurélien Mulliez, Matthieu Jabaudon, Vincent Sapin, Laurence Roszyk, André Labbé, Carole Egron, CHU Clermont-Ferrand, Pôle Pédiatrie, Centre Hospitalier Universitaire [Rennes], Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Medical Biochemistry and Molecular Biology, CHU Clermont-Ferrand, Délégation à la recherche clinique et aux innovations (DRCI), CHU de Clermont-Ferrand, Laboratoires d'Anatomie pathologique et de Physiologie, Université d'Auvergne - Clermont-Ferrand I (UdA), Faculté de Médecine - Clermont-Auvergne (FM - UCA), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Service de Biochimie et Génétique Moléculaire [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Laboratoire de Biochimie, Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, 0301 basic medicine, ARDS, MESH: Respiratory Sounds, Receptor for Advanced Glycation End Products, MESH: Bronchiolitis, Infection and Immunity, MESH: Hospitalization, Severity of Illness Index, Gastroenterology, Pathogenesis, 0302 clinical medicine, Recurrence, Prospective Studies, Respiratory system, soluble receptor for advanced glycation end-products, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, blood and urine biomarkers, infants, Prognosis, MESH: Infant, 3. Good health, Hospitalization, Acute Disease, Bronchiolitis, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Acute Disease, Biomarker (medicine), Female, Original Article, Pulmonary and Respiratory Medicine, medicine.medical_specialty, [SDV.BDLR.RA]Life Sciences [q-bio]/Reproductive Biology/Asexual reproduction, MESH: Prognosis, [SDV.BDLR.RS]Life Sciences [q-bio]/Reproductive Biology/Sexual reproduction, 03 medical and health sciences, soluble receptor for advanced glycation end‐products, recurrent wheezing, MESH: Severity of Illness Index, Internal medicine, Lower respiratory tract infection, medicine, Humans, Respiratory Sounds, Asthma, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, MESH: Humans, MESH: Receptor for Advanced Glycation End Products, business.industry, Infant, Original Articles, medicine.disease, MESH: Male, MESH: Prospective Studies, MESH: Recurrence, 030104 developmental biology, 030228 respiratory system, Pediatrics, Perinatology and Child Health, MESH: Biomarkers, lower respiratory tract infection, business, MESH: Female, Biomarkers, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Introduction Acute bronchiolitis is a major cause of acute respiratory distress in infants. The soluble receptor for advanced glycation end‐products (sRAGE) is a biomarker of pulmonary damage processes, with a diagnostic and a prognostic value in acute respiratory distress syndrome (ARDS). The RAGE pathway is also implicated in the pathogenesis of other respiratory diseases like asthma, but the value of sRAGE levels in acute bronchiolitis remains under‐investigated. Material and methods A prospective, observational, and analytical study was conducted at Clermont‐Ferrand University Hospital. The main objective was to evaluate the correlation between serum sRAGE and clinical severity of bronchiolitis in hospitalized infants aged
Published: 2018
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24. RAGE inhibition reduces acute lung injury in mice

Author: Raiko, Blondonnet, Jules, Audard, Corinne, Belville, Gael, Clairefond, Jean, Lutz, Damien, Bouvier, Laurence, Roszyk, Christelle, Gross, Marilyne, Lavergne, Marianne, Fournet, Loic, Blanchon, Caroline, Vachias, Christelle, Damon-Soubeyrand, Vincent, Sapin, Jean-Michel, Constantin, Matthieu, Jabaudon, Retinoids, Development and Developmental Diseases (R2D2), Université d'Auvergne - Clermont-Ferrand I (UdA), Université de Clermont-Ferrand, Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Biochimie et Génétique Moléculaire [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), CHU Gabriel Montpied [Clermont-Ferrand], and CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand]
Subjects: Male, Biopsy, Science, Acute Lung Injury, Receptor for Advanced Glycation End Products, Anti-Inflammatory Agents, Gene Expression, Severity of Illness Index, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Ion Channels, Article, Mice, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, Blood-Air Barrier, Antibodies, Monoclonal, respiratory system, Immunohistochemistry, Disease Models, Animal, Alveolar Epithelial Cells, Cytokines, Medicine, Blood Gas Analysis, Inflammation Mediators, Biomarkers
Abstract: International audience; The receptor for advanced glycation end-products (RAGE) is involved in inflammatory response during acute respiratory distress syndrome (ARDS). Growing body of evidence support strategies of RAGE inhibition in experimental lung injury, but its modalities and effects remain underinvestigated. Anesthetised C57BL/6JRj mice were divided in four groups; three of them underwent orotracheal instillation of acid and were treated with anti-RAGE monoclonal antibody (mAb) or recombinant soluble RAGE (sRAGE), acting as a decoy receptor. The fourth group served as a control. Lung injury was assessed by the analysis of blood gases, alveolar permeability, histology, AFC, and cytokines. Lung expression and distribution epithelial channels ENaC, Na,K-ATPase, and aquaporin (AQP)−5 were assessed. Treatment with either anti-RAGE mAb or sRAGE improved lung injury, arterial oxygenation and decreased alveolar inflammation in acid-injured animals. Anti-RAGE therapies were associated with restored AFC and increased lung expression of AQP-5 in alveolar cell. Blocking RAGE had potential therapeutic effects in a translational mouse model of ARDS, possibly through a decrease in alveolar type 1 epithelial cell injury as shown by restored AFC and lung AQP-5 expression. Further mechanistic studies are warranted to describe intracellular pathways that may control such effects of RAGE on lung epithelial injury and repair. Acute respiratory distress syndrome (ARDS) is a syndrome of diffuse inflammatory lung injury with increased pulmonary oedema and the rapid onset of hypoxemic respiratory failure 1. ARDS is still undertreated 2 , with high mortality and few effective therapies 3-5. RAGE is a membrane receptor that is expressed in alveolar type (AT)-1 epithelial cells of the lung and a marker of epithelial injury 6. There are many RAGE ligands, including high-mobility group box 1 protein (HMGB1), advanced glycation end-products (AGEs) and S100 protein 7, 8. RAGE controls a variety of cellular processes such as cell proliferation and migration, inflammation, apoptosis and microtubule stabilization 9. Its main soluble forms, referred to as soluble RAGE (sRAGE), include the extra-cellular domain of membrane RAGE (mRAGE) which is cleaved by proteinases and endogenous secretory RAGE (esRAGE, produced after alternative splicing) 10. In clinical ARDS, sRAGE has good diagnostic value and is associated with lung injury severity, impaired alveolar fluid clearance (AFC) and prognosis 6, 11-13. Impaired AFC is a major feature of ARDS that contributes to mortality 14. The main mechanism responsible for the resolution of alveolar oedema is ion transport across the alveolar epithelium, primarily through epithe-lial sodium (ENaC), Na,K-ATPase and aquaporin (AQP)-5 channels, thus creating a local osmotic gradient to reabsorb the water fraction of the oedema fluid from the airspaces of the lungs 15-17. Recent data support an effect of RAGE activation on ENaC activity in cultured AT-1 cells 18. However, in contrast to the situation in mice, the clearance of alveolar fluid after birth in humans may not critically depend on ENaC, at least in part because of greater reliance on other epithelial channels 15. The modulation of RAGE may reduce inflammatory responses in several models 19. Intratracheal administration of HMGB1 induced lung injury in mice and the pathological effects of intratracheal lipopolysaccharide (LPS) were partially ameliorated by systemic administration of anti-HMGB1 antibodies 8 , thereby implicating pattern-recognition receptors such as RAGE or toll-like receptors in the pathogenesis of ARDS. Experimental murine pulmonary ischemia followed by reperfusion caused lung injury that was ameliorated in mice treated with sRAGE and in RAGE −/− mice 20. Using a mouse model of lung
Published: 2017
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25. In vitro cytotoxic effects of DEHP-alternative plasticizers and their primary metabolites on a L929 cell line

Author: Teuta Eljezi, Pierre Pinta, Marie-Christine Chagnon, Damien Richard, Jean-Michel Chezal, Jérémy Pinguet, Valérie Sautou, Gaël Grimandi, Emmanuel Moreau, Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne ( IMoST ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Clermont Auvergne ( UCA ), CHU Clermont-Ferrand, Laboratoire d'ingénierie osteo-articulaire et dentaire ( LIOAD ), Université de Nantes ( UN ) -IFR26-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Pharmacologie Médicale [Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], Equipe NuTox (LNC - U1231) ( NUTOX ), Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Caractérisation et sécurité biologique des surfaces nanostructurées ( C-BIOSENSS ), Université d'Auvergne - Clermont-Ferrand I ( UdA ), Matériaux d'intérêt biologique, Université de Nantes ( UN ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Service Pharmacie [CHU Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Louise Michel [Clermont-Ferrand], Laboratoire d'ingénierie osteo-articulaire et dentaire (LIOAD), Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche en Gestion et en Economie (IREGE), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Service de Pharmacologie Médicale [CHU Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Caractérisation et sécurité biologique des surfaces nanostructurées (C-BIOSENSS), Université d'Auvergne - Clermont-Ferrand I (UdA), Regenerative Medicine and Skeleton research lab (RMeS), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-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), Regenerative Medicine and Skeleton (RMeS), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), CHU Louise Michel [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), and Jehan, Frederic
Subjects: 0301 basic medicine, Environmental Engineering, Metabolite synthesis, Biocompatibility, Cell Survival, Cytotoxicity, Health, Toxicology and Mutagenesis, Metabolite, Phthalic Acids, In Vitro Techniques, DEHP-alternative plasticizers, 010501 environmental sciences, 01 natural sciences, [ SDE ] Environmental Sciences, Mice, 03 medical and health sciences, chemistry.chemical_compound, Phthalates, Plasticizers, In vivo, Diethylhexyl Phthalate, Animals, Environmental Chemistry, Organic chemistry, Polyvinyl Chloride, Cells, Cultured, 0105 earth and related environmental sciences, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Chromatography, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Public Health, Environmental and Occupational Health, Plasticizer, Primary metabolite, Esters, General Medicine, General Chemistry, Fibroblasts, Pollution, In vitro, 3. Good health, Phthalic acid, 030104 developmental biology, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, chemistry
Abstract: IF 4.208; International audience; Phthalic acid esters have been widely used to improve the plasticity of PVC medical devices. They carry a high exposure risk for both humans and the environment in clinical situations. Our study focuses on the cytotoxicity of alternative plasticizers. Postulated primary metabolites were synthesized, not being commercially available. Cytotoxicity assays were performed on L929 murine cells according to the ISO-EN 10993-5 standard design for the biocompatibility of medical devices. The tested concentrations of plasticizers (0.01, 0.05 and 0.1 mg/ml) covered the range likely to be found in biological fluids coming into direct contact with the medical devices. DEHP, DINP and DINCH were cytotoxic at the highest concentration (0.1 mg/ml) for 7 days of exposure. Their corresponding metabolites were found to be more cytotoxic, for the same concentration. By contrast, TOTM and its corresponding metabolite MOTM were not found to be cytotoxic. DEHA showed no cytotoxicity, but its corresponding monoester (MEHA) produced a cytotoxic effect at 0.05 mg/ml. In clinical situations, medical devices can release plasticizers, which can come into contact with patients. In vivo, the plasticizers are quickly transformed into primary metabolites. It is therefore important to measure the effects of both the plasticizers and their corresponding metabolites. Standard first-line cytotoxicity assays should be performed to ensure biocompatibility.
Published: 2017
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26. S100B Blood Level Determination for Early Management of Ski-Related Mild Traumatic Brain Injury: A Pilot Study

Author: Samy Kahouadji, Pauline Salamin, Laurent Praz, Julien Coiffier, Vincent Frochaux, Julie Durif, Bruno Pereira, Lionel Arlettaz, Charlotte Oris, Vincent Sapin, Damien Bouvier, Service de Biochimie et Génétique Moléculaire [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, service de Biostatistiques, DRCI, Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], and Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: medicine.medical_specialty, Traumatic brain injury, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Poison control, Context (language use), S100B, ski, lcsh:RC346-429, mTBI (mild traumatic brain injury), 03 medical and health sciences, 0302 clinical medicine, medicine, 030212 general & internal medicine, lcsh:Neurology. Diseases of the nervous system, Original Research, Receiver operating characteristic, business.industry, Glasgow Coma Scale, Emergency department, medicine.disease, Polytrauma, ski accidents, Neurology, Biomarker (medicine), biomarker, Radiology, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: International audience; Background: Mild traumatic brain injury (mTBI) management in emergency departments is a complex process involving clinical evaluation, laboratory testing, and computerized tomography (CT) scanning. Protein S100B has proven to be a useful blood biomarker for early evaluation of mTBI, as it reduces the required CT scans by one-third. However, to date, the ability of S100B to identify positive abnormal findings in the CT scans of patients suffering from mTBI caused by ski practice has not been investigated. Thus, the primary aim of this study was to investigate the diagnostic performance of S100B as an mTBI management biomarker in patients with ski-related mTBI. Materials and Methods: One hundred and thirty adult mTBI patients presenting to the emergency department of Hôpital du Valais in Sion, Switzerland, with a Glasgow Coma Scale (GCS) score of 13-15 and clinical indication for a CT scan were included in the study. Blood samples for S100B measurement were collected from each patient and frozen in 3-hour post-injury intervals. CT scans were performed for all patients. Later, serum S100B levels were compared to CT scan findings in order to evaluate the biomarker's performance. Results: Of the 130 included cases of mTBI, 87 (70%) were related to ski practice. At the internationally established threshold of 0.1 μg/L, the receiver operating characteristic curve of S100B serum levels for prediction of abnormal CT scans showed 97% sensitivity, 11% specificity, and a 92% negative predictive value. Median S100B concentrations did not differ according to sex, age, or GCS score. Additionally, there was no significant difference between skiers and non-skiers. However, a statistically significant difference was found when comparing the median S100B concentrations of patients who suffered fractures or had polytrauma and those who did not suffer fractures. Conclusion: The performance of S100B in post-mTBI brain lesion screenings seems to be affected by peripheral lesions and/or ski practice. The lack of neurospecificity of the biomarker in this context does not allow unnecessary CT scans to be reduced by one-third as expected.
Published: 2020
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27. Do Bevacizumab solutions interact during an infusion through implantable venous access ports with silicone or polyurethane catheters ?

Author: Tokhadze, Nicolas, Chennell, Philip, Cueff, Régis, Sautou, Valérie, CHU Clermont-Ferrand, Institut de Chimie de Clermont-Ferrand (ICCF), SIGMA Clermont (SIGMA Clermont)-Institut de Chimie du CNRS (INC)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Service Pharmacie [CHU Clermont-Ferrand], CHU Louise Michel [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], and CHU Clermont-Ferrand-CHU Louise Michel [Clermont-Ferrand]
Subjects: interfaces, Content-container interactions, content–container interactions, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, implantable venous access port, catheter, bevacizumab, stability, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, [SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials, [SPI.MAT]Engineering Sciences [physics]/Materials
Abstract: International audience; This work aims to evaluate the possible impact of interactions between bevacizumab solutions and an implantable port equipped with a silicone or a polyurethane catheter after infusion through a complete infusion setup in simulated use conditions. Physicochemical and structural stability of bevacizumab solution was assessed by: visual examination, subvisible particles counting, dynamic light scattering, size exclusion chromatography and ion exchange chromatography. Mechanical properties of the catheters were evaluated by measuring Shore-A hardness, strain at break, strain at stress and Young's modulus. The physicochemical surface state of the catheters was assessed by FTIR-ATR spectroscopy, scanning electron microscopy (SEM) and by water contact angle measurement. Analysis of the bevacizumab solution did not highlight any signs of instability or loss of active substance. Mechanical properties of both materials remained unchanged after the infusion. During material analysis, a decrease of water contact angle observed after infusion and was more pronounced for polyurethane catheters than for silicone's, possibly due to bevacizumab adsorption or possible leachable extraction from the materials. Surface modifications were also noticed by SEM. This study did not highlight any modifications that could alter the quality of the bevacizumab infusion, nor of the infusion catheter in polyurethane or silicone, despite a modification of surface hydrophilicity. Even if after a single infusion implantable ports remained safe to use, they aim to be used for several infusion of various drugs during its lifetime, and further studies are needed to assess the impact of repeated infusions.
Published: 2019
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28. Les entretiens entre patients et professionnels de santé : éléments de construction collective des discours

Author: Blasco, Mylène, Advocat, Océane, Durif, Franck, Laboratoire de Recherche sur le Langage (LRL), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Service de Neurologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, CHU Estaing [Clermont-Ferrand], and CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand]
Subjects: linguistique appliquée, entretiens médicaux, syntaxe, Linguistique de corpus, [SHS.LANGUE]Humanities and Social Sciences/Linguistics, [SHS]Humanities and Social Sciences
Abstract: International audience; L’expertise linguistique de corpus oraux enregistrés et rigoureusement transcrits, entre un patient et un professionnel de la santé, permet d’identifier un ensemble de phénomènes linguistiques qui nous renseignent sur la manière dont la communication procède dans un échange institutionnel en contexte hospitalier. Notre travail – qui s’inscrit dans la lignée des travaux sur la syntaxe de données orales attestées – vise à caractériser le discours oral du médecin et à identifier les usages remarquables de langue dans son échange avec le patient. Enfin, nous montrons de quelle manière les soignants et les soignés collaborent et construisent conjointement les discours sur et autour de la pathologie. Dans cette étude linguistique d’entretiens en santé, la syntaxe de la langue parlée fait émerger, de manière collective ou non, des informations implicites. Nous avons à cœur de mettre en lien différents mécanismes linguistiques les plus subtiles avec leur valeur d’emploi dans le discours. L’entrée par la syntaxe est originale, il s’agit de saisir le travail du soin dans ses dimensions linguistique et communicationnelle pour donner des pistes que les médecins pourraient exploiter dans leur pratique professionnelle.
Published: 2019

29. Comparative effectiveness of teriflunomide vs dimethyl fumarate in multiple sclerosis

Author: Patrick Vermersch, Ivania Patry, Nicolas Maubeuge, Catherine Lubetzki, Ofsep Study Groups, David-Axel Laplaud, Bruno Stankoff, Bruno Brochet, Eric Thouvenot, Céline Labeyrie, Jean-Philippe Camdessanché, Olivier Gout, Laure Michel, Chantal Nifle, Abdullatif Al Khedr, Emmanuelle Leray, Gilles Edan, Marc Debouverie, Laetitia Barbin, David Brassat, Yohann Foucher, Thibault Moreau, Romain Casey, Jean Pelletier, Christine Lebrun-Frenay, Sandra Vukusic, Laurent Magy, Olivier Heinzlef, Philippe Cabre, Caroline Papeix, Ayman Tourbah, Gilles Defer, Abir Wahab, Pierre Clavelou, Eric Berger, Jérôme De Seze, A.-M. Guennoc, Fabien Rollot, Olivier Casez, Sandrine Wiertlewski, Thomas Debroucker, Pierre Labauge, Bertrand Bourre, 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), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Service de Neurologie [Lyon], CHU Lyon, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie, Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Service de neurologie [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Inflammation: mécanismes et régulation et interactions avec la nutrition et les candidoses, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Service de neurologie [Rennes], Université de Rennes (UR), Department of Neurology, Centre Hospitalier Universitaire de Nice (CHU Nice), Service de Neurologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Service de neurologie [Reims], Centre Hospitalier Universitaire de Reims (CHU Reims), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU de la Martinique [Fort de France], CHU Pitié-Salpêtrière [AP-HP], Public Health Agency of Canada, CHI Poissy-Saint-Germain, Service de Neurologie [CHU de Poissy], CHU De Poissy, Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre de Recherches Critiques sur le Droit (CERCRID), Université Lumière - Lyon 2 (UL2)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), Fondation Ophtalmologique Adolphe de Rothschild [Paris], 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), Service de Neurologie [CHU Limoges], CHU Limoges, Service de Neurologie [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), Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), École des Hautes Études en Santé Publique [EHESP] (EHESP), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Supported by Fondation ARSEP, CHU Nantes (Appel d’Offre Interne), and Association ANTARES. The French Observatoire of Multiple Sclerosis is supported by a grant provided by the French State and handled by the Agence Nationale de la Recherche, within the framework of the Investments for the Future program, under the reference ANR-10-COHO-002. The study was supported by West Neurosciences Network and Société Francophone de Scl´erose en Plaques, Fondation ARSEP, and by Appel d’Offre Interne du CHU de Nantes., SFSEP and OFSEP groups : Fontaine B, Marignier R, Durand-Dubief F, Mathey G, Le Page E, Peaureaux-Averseng D, Ouallet JC, Ruet A, Collongues N, Hautecoeur P, Zephir H, Maillard E, Cohen M, Derache N, Branger P, Ayrignac X, Carra-Dalliere C, Fromont A, Chamard-Witkowski L, Taithe F, Moisset X, Audoin B, Rico-Lamy A, Castelnovo G, Giannesini C, Fagniez O, Bensa C, Gueguen A, Kasonde IT, De Vilmarest A, Montcuquet A, Vaillants M, Beltran S, Creange A, Ayache S, Abdellaoui M, Pottier C, Slesari I, Deburghraeve V, Neau JP, Servan J, Pico F, Henry C, Hankiewicz K., Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Service de neurologie, Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), CHU 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 [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Département de Neurologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-IFR70-CHU Pitié-Salpêtrière [APHP], CHU Pitié-Salpêtrière [APHP], Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM)-Université Lumière - Lyon 2 (UL2), Fondation Ophtalmologique Rothschild, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Université de Montpellier (UM)-Université Montpellier 1 (UM1), Le Bihan, Sylvie, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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 Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Université de Lille, Droit et Santé-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), 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), Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Neuro-Dol (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], and Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)
Subjects: Adult, Male, medicine.medical_specialty, Toluidines, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Hydroxybutyrates, Effectiveness, Dimethyl fumarate, Multiple sclerosis, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Recurrence, Internal medicine, Teriflunomide, Nitriles, medicine, Humans, 030212 general & internal medicine, 10. No inequality, Adverse effect, ComputingMilieux_MISCELLANEOUS, Intention-to-treat analysis, Expanded Disability Status Scale, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Fingolimod Hydrochloride, Odds ratio, Middle Aged, Discontinuation, Treatment Outcome, chemistry, Crotonates, Propensity score matching, Disease Progression, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Immunosuppressive Agents, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: ObjectiveIn this study, we compared the effectiveness of teriflunomide (TRF) and dimethyl fumarate (DMF) on both clinical and MRI outcomes in patients followed prospectively in the Observatoire Français de la Sclérose en Plaques.MethodsA total of 1,770 patients with relapsing-remitting multiple sclerosis (RRMS) (713 on TRF and 1,057 on DMF) with an available baseline brain MRI were included in intention to treat. The 1- and 2-year postinitiation outcomes were relapses, increase of T2 lesions, increase in Expanded Disability Status Scale score, and reason for treatment discontinuation. Propensity scores (inverse probability weighting) and logistic regressions were estimated.ResultsThe confounder-adjusted proportions of patients were similar in TRF- compared to DMF-treated patients for relapses and disability progression after 1 and 2 years. However, the adjusted proportion of patients with at least one new T2 lesion after 2 years was lower in DMF compared to TRF (60.8% vs 72.2%, odds ratio [OR] 0.60, p < 0.001). Analyses of reasons for treatment withdrawal showed that lack of effectiveness was reported for 8.5% of DMF-treated patients vs 14.5% of TRF-treated patients (OR 0.54, p < 0.001), while adverse events accounted for 16% of TRF-treated patients and 21% of DMF-treated patients after 2 years (OR 1.39, p < 0.001).ConclusionsAfter 2 years of treatment, we found similar effectiveness of DMF and TRF in terms of clinical outcomes, but with better MRI-based outcomes for DMF-treated patients, resulting in a lower rate of treatment discontinuation due to lack of effectiveness.Classification of evidenceThis study provides Class III evidence that for patients with RRMS, TRF and DMF have similar clinical effectiveness after 2 years of treatment.
Published: 2019
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30. Specific lumbar puncture training during clinical clerkship durably increases atraumatic needle use

Author: Bruno Pereira, Xavier Moisset, Alexandre Saturnin, Carole Jamet, Pierre Clavelou, Service de Neurologie [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Neuro-Dol (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], and Bodescot, Myriam
Subjects: Clinical clerkship, Male, Critical Care and Emergency Medicine, Students, Medical, Medical Doctors, Objective structured clinical examination, Physiology, Health Care Providers, Normal Distribution, Social Sciences, Pathology and Laboratory Medicine, Nervous System, Infographics, Spinal Puncture, 0302 clinical medicine, Learning and Memory, Sociology, Surveys and Questionnaires, Medicine and Health Sciences, Psychology, 030212 general & internal medicine, Medical Personnel, Cerebrospinal Fluid, Multidisciplinary, medicine.diagnostic_test, Education, Medical, Headaches, Clinical Clerkship, Charts, 3. Good health, Body Fluids, Professions, Needles, Clinical training, Physical Sciences, Medicine, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Clinical Competence, Clinical competence, Anatomy, Human learning, Research Article, medicine.medical_specialty, Computer and Information Sciences, Science, education, Education, 03 medical and health sciences, Human Learning, Young Adult, Signs and Symptoms, Diagnostic Medicine, Physicians, medicine, Learning, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Lumbar puncture, business.industry, Data Visualization, Cognitive Psychology, Biology and Life Sciences, Probability Theory, Probability Distribution, Health Care, Medical Education, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Case-Control Studies, People and Places, Physical therapy, Cognitive Science, Population Groupings, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Medical Humanities, 030217 neurology & neurosurgery, Mathematics, Neuroscience
Abstract: BackgroundAtraumatic needles are proposed to lower complication rates after lumbar puncture (LP). Only a minority of physicians use such needles. Here we aimed to assess the impact of specific training in LP during clinical clerkship on the proportion of medical students using atraumatic needles.MethodsWe performed a case-control study comparing medical students undergoing clinical clerkship and students undergoing specific LP training. The 176 students of a class underwent training in LP just before beginning their clinical rotations. This training consisted of 45 minutes of theoretical training and a 90-minute practical session with a dummy. Twenty students were selected from the class at random, and their competence was assessed with a multiple choice questionnaire (MCQ) and an objective structured clinical examination (OSCE), nine months after the specific training. These 20 cases were compared with 20 students randomly selected from a class of 180 students who had not undergone specific training in LP and were at the end of their clinical clerkship.ResultsWe found that 60% of the students with specific training and 25% of those with classic clinical training used an atraumatic needle during the OSCE (p = 0.025). The mean MCQ (/100) scores obtained were 57±15 and 60±15 for the specific and classic training groups, respectively (p = 0.35). Overall OSCE score was similar in the two groups (63.5±9.3 vs. 65.8±9.3; p = 0.20).ConclusionVery few practicing physicians use atraumatic needles, which limits the teaching of their use to medical students. Specific training durably increases the use of appropriate needles.
Published: 2019
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31. New SPE-LC-MS/MS method for the simultaneous determination in urine of 22 metabolites of DEHP and alternative plasticizers from PVC medical devices

Author: Nicolas Kerckhove, Valérie Sautou, Laurent Storme, Teuta Eljezi, Benoît Boeuf, Emmanuel Moreau, Lise Bernard, Morgane Masse, Bertrand Décaudin, Stéphanie Genay, Jérémy Pinguet, Damien Richard, Céline Lambert, Service de Pharmacologie Médicale [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Neuro-Dol (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand, Institut de Chimie de Clermont-Ferrand (ICCF), SIGMA Clermont (SIGMA Clermont)-Institut de Chimie du CNRS (INC)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Unité Biostatistique, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Pharmacie [CHU Clermont-Ferrand], CHU Louise Michel [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], Service de Réanimation Pédiatrique et Péri-natalogie, CHU Estaing [Clermont-Ferrand], Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 (GRITA), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHRU Lille, Institut de Pharmacie, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Environnement périnatal et croissance - EA 4489 (EPS), CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Louise Michel [Clermont-Ferrand], and CCSD, Accord Elsevier
Subjects: [SDV]Life Sciences [q-bio], 02 engineering and technology, Urine, Tandem mass spectrometry, 01 natural sciences, High-performance liquid chromatography, Urinary metabolite, Analytical Chemistry, chemistry.chemical_compound, Plasticizers, Tandem Mass Spectrometry, Intensive care, Diethylhexyl Phthalate, Biomonitoring, Humans, Polyvinyl Chloride, Chromatography, Alternative plasticizers, Chemistry, 010401 analytical chemistry, Solid Phase Extraction, Plasticizer, Phthalate, 021001 nanoscience & nanotechnology, 0104 chemical sciences, 3. Good health, [SDV] Life Sciences [q-bio], Human biomonitoring, Medical devices, SPE-LC-MS/MS, 0210 nano-technology, Glucuronide, Chromatography, Liquid
Abstract: International audience; DiEthylHexylPhthalate (DEHP) can leach out of plasticized PVC medical devices (MD) and may enter into contact with patients. This phthalate is known for its reprotoxic and endocrine disrupting effects. Its use in medical devices (MD) has been restricted and alternative plasticizers have been developed. Nevertheless, no published clinical studies exist concerning patient exposure to these alternative plasticizers during medical care. This is particularly worrisome when high-risk populations, such as newborns, are exposed to these new plasticizers in intensive care units. Our study aimed to develop a novel sensitive and selective method to simultaneously identify and quantify DEHP and 17 other plasticizer metabolites (free or glucuronide conjugates), which are specific biomarkers of DEHTP, TOTM, DINP, DINCH and DEHA exposure in human urine. This robust method uses turbulent-flow online extraction technology coupled to high performance liquid chromatography – tandem mass spectrometry. Special care was taken to address two major problems in plasticizer analysis: contamination and chromatographic separation of interfering analogue structures. The validation was assessed in synthetic urine and the linearity of response was demonstrated for all compounds (R2 > 0.99), with limits of quantification from 0.01 to 0.1 ng/ml. Accuracies ranged from 86% to 117% and inter- and intra-day precisions were
Published: 2019
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32. Immunization and multiple sclerosis: Recommendations from the French Multiple Sclerosis Society

Author: C. Lebrun, S. Vukusic, V. Abadie, C. Achour, F. Ader, H. Alchaar, A. Alkhedr, F. Andreux, G. Androdias, R. Arjmand, B. Audoin, D. Audry, D. Aufauvre, C. Autreaux, X. Ayrignac, M. Bailbe, M. Benazet, C. Bensa, D. Bensmail, E. Berger, P. Bernady, Y. Bertagna, D. Biotti, A. Blanchard-Dauphin, J. Bonenfant, M. Bonnan, B. Bonnemain, F. Borgel, E. Botelho-Nevers, S. Boucly, B. Bourre, C. Boutière, P. Branger, D. Brassat, S. Bresch, V. Breuil, B. Brochet, H. Brugeilles, P. Bugnon, P. Cabre, J.-P. Camdessanché, C. Carra-Dalière, O. Casez, J.-M. Chamouard, B. Chassande, P. Chataignier, M. Chbicheb, A. Chenet, J. Ciron, P. Clavelou, M. Cohen, R. Colamarino, N. Collongues, I. Coman, P.-R. Corail, S. Courtois, M. Coustans, A. Creange, E. Creisson, N. Daluzeau, C. Davenas, J. De Seze, M. Debouverie, R. Depaz, N. Derache, L. Divio, X. Douay, C. Dulau, F. Durand-Dubief, G. Edan, Z. Elias, O. Fagniez, M. Faucher, J.-M. Faucheux, M. Fournier, A. Gagneux-Brunon, P. Gaida, P. Galli, P. Gallien, J. Gaudelus, D. Gault, A. Gayou, M. Genevray, A. Gentil, J. Gere, L. Gignoux, M. Giroux, P. Givron, O. Gout, J. Grimaud, A.-M. Guennoc, N. Hadhoum, P. Hautecoeur, O. Heinzlef, M. Jaeger, S. Jeannin, L. Kremer, A. Kwiatkowski, P. Labauge, C. Labeyrie, S. Lachaud, I. Laffont, C. Lanctin-Garcia, J. Lannoy, L. Lanotte, D. Laplaud, D. Latombe, M. Lauxerois, E. Le Page, C. Lebrun-Frenay, P. Lejeune, P. Lejoyeux, B. Lemonnier, E. Leray, C.-M. Loche, C. Louapre, C. Lubetzki, A. Maarouf, B. Mada, L. Magy, E. Maillart, E. Manchon, R. Marignier, P. Marque, G. Mathey, A. Maurousset, C. Mekies, M. Merienne, L. Michel, A.-M. Milor, X. Moisset, A. Montcuquet, T. Moreau, N. Morel, M. Moussa, J.-P. Naudillon, M. Normand, P. Olive, J.-C. Ouallet, O. Outteryck, C. Pacault, C. Papeix, I. Patry, D. Peaureaux, J. Pelletier, B. Pichon, S. Pittion, E. Planque, M.-C. Pouget, V. Pourcher, C. Radot, I. Robert, F. Rocher, A. Ruet, C. Saint-Val, J.-Y. Salle, A. Salmon, E. Sartori, S. Schaeffer, B. Stankhof, F. Taithe, E. Thouvenot, C. Tizon, A. Tourbah, P. Tourniaire, M. Vaillant, P. Vermersch, S. Vidil, A. Wahab, M.-H. Warter, S. Wiertlewski, B. Wiplosz, B. Wittwer, C. Zaenker, H. Zephir, Université Côte d'Azur (UCA), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hosp Civils Lyon, Serv Malad Infect, Lyon, France, Biogéosciences [UMR 6282] [Dijon] (BGS), Centre National de la Recherche Scientifique (CNRS)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Pontchaillou [Rennes], CHU Saint-Etienne, Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - AP-HM] (CEMEREM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)- Hôpital de la Timone [CHU - APHM] (TIMONE), Comité de Développement Horticole du Centre Val de Loire (CDHRC), Génétique, physiopathologie et ingénierie du tissu osseux (GéPITOS), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Service d'Etudes du Comportement des Matériaux de Conditionnement (SECM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Galaxies, Etoiles, Physique, Instrumentation (GEPI), Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [Rennes] = Neurology [Rennes], Excitabilité nerveuse et thérapeutique (ENT), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-EA 4391, Service de Physiologie Explorations Fonctionnelles-Hôpital Henri Mondor, Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), RMN et optique : De la mesure au biomarqueur, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Combustion Research Facility, Sandia National Laboratories - Corporation, Service de Pédiatrie [Jean Verdier], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Kuriwa Observatory, Fondation Ophtalmologique Adolphe de Rothschild [Paris], Laboratoire de Mécanique, Modélisation et Procédés Propres (M2P2), Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Euromov (EuroMov), Université de Montpellier (UM), 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), Université Nice Sophia Antipolis - Faculté de Médecine (UNS UFR Médecine), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), École des Hautes Études en Santé Publique [EHESP] (EHESP), Département Méthodes quantitatives en santé publique (METIS), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-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)-Centre National de la Recherche Scientifique (CNRS), Biologie des Interactions Neurones / Glie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-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), Service de Neurologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laboratoire d'automatique et de génie des procédés (LAGEP), Université de Lyon-Université de Lyon-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Haras National Suisse, Centre Hospitalier Universitaire de Reims (CHU Reims), Center for health studies, Service de neurologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Hospices Civils de Lyon, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Biogéosciences [UMR 6282] (BGS), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Hôpital Henri Mondor-EA 4391, Service de Physiologie Explorations Fonctionnelles-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - APHM] (CEMEREM), Comité de développement horticole de la région Centre-Val-de-Loire (CDHR CENTRE-VAL-DE-LOIRE), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)- Hôpital de la Timone [CHU - APHM] (TIMONE), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Jean Verdier [AP-HP], 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)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Université Côte d'Azur (UCA), Service de Neurologie [Rennes], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Institut d’Électronique, de Microélectronique et de Nanotechnologie (IEMN) - UMR 8520 (IEMN), Ecole Centrale de Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA), Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de Neurologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-IFR70-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie, CHU Clermont-Ferrand, Hôpital Jean Minjoz, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: medicine.medical_specialty, Vaccination schedule, MEDLINE, Scientific literature, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, Recurrence, Risk Factors, Health care, Medicine, Humans, 030212 general & internal medicine, Immunization Schedule, Societies, Medical, Vaccines, business.industry, Risk of infection, Prevention, Vaccination, medicine.disease, 3. Good health, Neurology, Immunization, Family medicine, Evidence-Based Practice, Practice Guidelines as Topic, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology (clinical), France, business, Infection, Vaccine, 030217 neurology & neurosurgery
Abstract: Objectives To establish recommendations on immunization for patients with multiple sclerosis (MS). Background Vaccines have been suspected in the past to trigger MS and relapses. With the extension of the immunoactive treatment arsenal, other concerns have been raised more recently about an increased risk of infection or a decreased effectiveness of immunization in immunosuppressed patients. Methods The French Group for Recommendations into Multiple Sclerosis (France4MS) performed a systematic search of papers in Medline and other university databases (January 1975–June 2018). The RAND/UCLA appropriateness method was chosen to review the scientific literature and to formalize the degree of agreement among experts on 5 clinical questions related to immunization and MS. Readers from the steering committee conducted a systematic analysis, wrote a critical synthesis and prepared a list of proposals that were evaluated by a rating group of 28 MS experts. The final version of the recommendations was finally reviewed by a reading group of 110 health care professionals and classified as appropriate, inappropriate or uncertain. Results Neurologists should verify the vaccination status as soon as MS is diagnosed and before disease-modifying treatments (DMTs) are introduced. The French vaccination schedule applies to MS patients and seasonal influenza vaccination is recommended. In the case of treatment-induced immunosuppression, MS patients should be informed about the risk of infection and the vaccination standards of the French High Council of Health should be applied. Live attenuated vaccines are contra-indicated in patients recently treated with immunosuppressive drugs, including corticosteroids; other vaccines can be proposed whatever the treatment, but their effectiveness may be partly reduced with some drugs. Conclusion Physicians and patients should be aware of the updated recommendations for immunizations of patients with MS.
Published: 2019
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33. Fetal fibronectin test for threatened preterm delivery 48h after admission: Cost-effectiveness study

Author: Anne Debost-Legrand, Charline Mourgues, Nathalie Favre, Denis Gallot, Amélie Delabaere, Amélie Rossi, Vincent Sapin, Laurence Roszyk, Thérapie guidée par l'image (TGI), Institut Pascal (IP), 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), Institut de recherches sur la catalyse et l'environnement de Lyon (IRCELYON), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Service de Biochimie et Génétique Moléculaire [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Laboratoire de Biochimie, Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Pôle Entrepreneuriat et Innovation - Rouen Business School, Rouen Business School, CHU Gabriel Montpied [Clermont-Ferrand], and CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand]
Subjects: Adult, medicine.medical_specialty, Cost effectiveness, Cost-Benefit Analysis, Gestational Age, Fetal Fibronectin Test, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Tertiary care, Crown-Rump Length, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, Pregnancy, medicine, Humans, 030212 general & internal medicine, Early discharge, Preterm delivery, ComputingMilieux_MISCELLANEOUS, 030219 obstetrics & reproductive medicine, Fetal fibronectin, Obstetrics, business.industry, Obstetrics and Gynecology, Imaging Procedures, Cost-effectiveness analysis, Length of Stay, Patient Discharge, Fibronectins, 3. Good health, Reproductive Medicine, Cervical Length Measurement, Premature Birth, Female, business
Abstract: OBJECTIVE The aim of this work was to assess the cost-effectiveness of the fetal fibronectin (fFN) test at 48 h after admission for threatened preterm delivery to promote early discharge. STUDY DESIGN Before-and-after study to calculate the incremental cost-effectiveness ratio (ICER). Patients were enrolled 48 h after admission in a tertiary care centre for threatened preterm delivery between 24+0 and 34+6 weeks. fFN testing was performed. During the first period, physician was blinded to fFN test and discharge occurred after apparent reduced symptomatology at physician's discretion. During the second period, fFN test was revealed to physician and discharge was immediately proposed to negative test patients. The costs considered in this analysis were the direct medical costs from the hospital perspective: costs of hospitalisation, treatment, and imaging procedures. The efficacy criterion selected was the number of deliveries at 7 and at 14 days after admission for threatened preterm delivery. RESULTS The study included 178 pregnant patient, 99 during the first period (July 2008-October 2009) and 79 during the second (March 2010-February 2012). The lengths of hospital stays were shorter during the second period, with more than 50% of women discharged home between 48 and 72 h (p
Published: 2019
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34. Implication of the SH3TC2 gene in Charcot-Marie-Tooth disease associated with deafness and/or scoliosis: Illustration with four new pathogenic variants

Author: C. Dejoie, Justine Lerat, Cyril Goizet, Annick Toutain, M. Rego, P. Beze Beyrie, Corinne Magdelaine, F. Taithe, Jon Andoni Urtizberea, P Calvas, A. Delaubrier, Hubert Journel, Eric Bieth, Brigitte Gilbert-Dussardier, Hélène Dzugan, Laurent Magy, F. Demurger, F. Laffargue, Franck Sturtz, A. Lunati, Pascal Cintas, Anne-Sophie Lia, Service d'Oto-rhino-laryngologie (ORL) et chirurgie cervico-faciale [CHU Limoges], CHU Limoges, Maintenance Myélinique et Neuropathies Périphériques (MMNP), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Service de Biochimie et Génétique Moléculaire [CHU Limoges], Centre hospitalier de Pau, Service de Génétique Médicale, CHU Toulouse, Toulouse, France., CHU Toulouse, Departement de Neurologie, Service de Médecine Physique et rééducation - CHU Poitiers, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de Génétique Médicale - Centre Hospitalier Bretagne Atlantique, Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Cibles moléculaires et thérapeutiques de la maladie d'Alzheimer (CIMoTHeMA), Université de Poitiers, Service Génétique Médicale [CHU Poitiers], Service de neurogénétique - CHU Bordeaux, CHU Bordeaux [Bordeaux], Service génétique Médicale - Centre Hospitalier Bretagne Atlantique, Service de Génétique Médicale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service de Neurologie [CHU Limoges], Centre de référence national neuropathies périphériques rares [CHU Limoges], Service de Neurologie [CHU Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Laboratoire de Génétique Moléculaire [CHU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre compétence neuromusculaire, APHP, Centre Hospitalier Hendaye, CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)
Subjects: Adult, Male, Charcot-Marie-Tooth, Hearing loss, media_common.quotation_subject, [SDV]Life Sciences [q-bio], Nonsense, Scoliosis, Deafness, Cohort Studies, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Charcot-Marie-Tooth Disease, SH3TC2, Medicine, Missense mutation, Humans, 030212 general & internal medicine, Child, Gene, media_common, Aged, Genetics, business.industry, Intracellular Signaling Peptides and Proteins, Genetic Variation, Middle Aged, medicine.disease, Phenotype, 3. Good health, Neuropathy, Peripheral neuropathy, Neurology, NGS, Mutation, Female, Neurology (clinical), France, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: International audience; The autosomal recessive demyelinating form of Charcot-Marie-Tooth can be due to SH3TC2 gene pathogenic variants (CMT4C, AR-CMTde-SH3TC2). We report on a series of 13 patients with AR-CMTde-SH3TC2 among a French cohort of 350 patients suffering from all type of inheritance peripheral neuropathy. The SH3TC2 gene appeared to be the most frequently mutated gene for demyelinating neuropathy in this series by NGS. Four new pathogenic variants have been identified: two nonsense variants (p.(Tyr970*), p.(Trp1199*)) and two missense variants (p.(Leu1126Pro), p.(Ala1206Asp)). The recurrent variant p.Arg954* was present in 62%, and seems to be a founder mutation. The phenotype is fairly homogeneous, as all these patients, except the youngest ones, presented scoliosis and/or hearing loss.
Published: 2019
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35. Advanced Glycation End Products and Receptor (RAGE) Promote Wound Healing of Human Corneal Epithelial Cells

Author: Helena Choltus, Raiko Blondonnet, Loïc Blanchon, Frédéric Chiambaretta, Marilyne Lavergne, Matthieu Jabaudon, Vincent Sapin, Jean-Michel Constantin, Corinne Belville, Christelle Gross, BLANCHON, LOIC, Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Service d'Ophtalmologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service de Biochimie et Génétique Moléculaire [CHU Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Estaing [Clermont-Ferrand], and CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand]
Subjects: Glycation End Products, Advanced, 0301 basic medicine, Small interfering RNA, Receptor for Advanced Glycation End Products, wound healing, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, HMGB1, AGEs, Cell Line, RAGE (receptor), Cornea, 03 medical and health sciences, 0302 clinical medicine, Cell Movement, Glycation, medicine, Humans, RNA, Messenger, HMGB1 Protein, RNA, Small Interfering, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Cells, Cultured, Cell Proliferation, Corneal epithelium, corneal epithelium, Dose-Response Relationship, Drug, biology, business.industry, Epithelium, Corneal, NF-kappa B, Epithelial Cells, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Cell migration, RAGE, 030104 developmental biology, medicine.anatomical_structure, [SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Connexin 43, 030221 ophthalmology & optometry, biology.protein, Cancer research, sense organs, Signal transduction, Wound healing, business, Corneal Injuries, Signal Transduction
Abstract: International audience; Purpose We used a human corneal epithelial cell (HCE) line to determine the involvement of the advanced glycation end products (AGEs) / receptor for AGEs (RAGE) couple in corneal epithelium wound healing. Methods After wounding, HCE cells were exposed to two major RAGE ligands (HMGB1 and AGEs), and wound healing was evaluated using the in vitro scratch assay. Following wound healing, the HCE cells were used to study the influence of the RAGE ligands on HCE proliferation, invasion, and migration. Activation of the nuclear factor (NF)-κB signaling pathway by the AGEs/RAGE couple was tested using a luciferase reporter assay. Functional transcriptional regulation by this pathway was confirmed by quantification of expression of the connexin 43 target gene. For each experiment, specific RAGE involvement was confirmed by small interfering RNA treatments. Results AGEs treatment at a dose of 100 µg/mL significantly improved the wound healing process in a RAGE-dependent manner by promoting cell migration, whereas HMGB1 had no effect. No significant influence of the AGEs/RAGE couple was observed on cell proliferation and invasion. However, this treatment induced an early activation of the NF-κB pathway and positively regulated the expression of the target gene, connexin 43, at both the mRNA and protein levels. Conclusions Our results demonstrate that the RAGE pathway is activated by AGEs treatment and is involved in the promotion of corneal epithelial wound healing. This positive action is observed only during the early stages of wound healing, as illustrated by the quick activation of the NF-κB pathway and induction of connexin 43 expression.
Published: 2020
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36. Effects of flow rate on the migration of different plasticizers from PVC infusion medical devices

Author: Lise Bernard, Teuta Eljezi, Hélène Clauson, Céline Lambert, Yassine Bouattour, Philip Chennell, Bruno Pereira, Valérie Sautou, ARMED Study Group, Institut de Chimie de Clermont-Ferrand (ICCF), SIGMA Clermont (SIGMA Clermont)-Institut de Chimie du CNRS (INC)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), CHU Clermont-Ferrand, Service Pharmacie [CHU Clermont-Ferrand], CHU Louise Michel [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], and CHU Clermont-Ferrand-CHU Louise Michel [Clermont-Ferrand]
Subjects: Contact time, Polymers, [SDV]Life Sciences [q-bio], lcsh:Medicine, 02 engineering and technology, 010501 environmental sciences, MESH: Plasticizers, 01 natural sciences, Mass Spectrometry, Analytical Chemistry, chemistry.chemical_compound, Spectrum Analysis Techniques, Plasticizers, Infusion Procedure, Medicine and Health Sciences, lcsh:Science, Polyvinyl Chloride, Flow Rate, Multidisciplinary, Chemistry, Pharmaceutics, Organic Compounds, Physics, Chromatographic Techniques, Classical Mechanics, MESH: Equipment and Supplies, 021001 nanoscience & nanotechnology, Hospitals, 3. Good health, Volumetric flow rate, Intensive Care Units, Macromolecules, Equipment and Supplies, Physical Sciences, Chloroform, 0210 nano-technology, Research Article, Biotechnology, Drug Administration, Patients, Materials by Structure, Materials Science, MESH: Polyvinyl Chloride, Fluid Mechanics, Research and Analysis Methods, Continuum Mechanics, Gas Chromatography-Mass Spectrometry, Drug Therapy, Intensive care, Humans, 0105 earth and related environmental sciences, Inpatients, MESH: Humans, lcsh:R, Significant difference, Organic Chemistry, Plasticizer, Chemical Compounds, Biology and Life Sciences, Fluid Dynamics, Polymer Chemistry, Pvc matrix, Health Care, Polyvinyl chloride, Health Care Facilities, lcsh:Q, Medical Devices and Equipment, MESH: Intensive Care Units, Biomedical engineering
Abstract: International audience; Infusion medical devices (MDs) used in hospitals are often made of plasticized polyvinylchloride (PVC). These plasticizers may leach out into infused solutions during clinical practice, especially during risk-situations, e.g multiple infusions in Intensive Care Units and thus may enter into contact with the patients. The migrability of the plasticizers is dependent of several clinical parameters such as temperature, contact time, nature of the simulant, etc… However, no data is available about the influence of the flow rate at which drug solutions are administrated. In this study, we evaluated the impact of different flow rates on the release of the different plasticizers during an infusion procedure in order to assess if they could expose the patients to more toxic amounts of plasticizers. Migration assays with different PVC infusion sets and extension lines were performed with different flow rates that are used in clinical practice during 1h, 2h, 4h, 8h and 24h, using a lipophilic drug simulant. From a clinical point of view, the results showed that, regardless of the plasticizer, the faster the flow rate, the higher the infused volume and the higher the quantities of plasticizers released, both from infusion sets and extension lines, leading to higher patient exposure. However, physically, there was no significant difference of the migration kinetics linked to the flow rate for a same medical device, reflecting complex interactions between the PVC matrix and the simulant. The migration was especially dependent on the nature and the composition of the medical device.
Published: 2018
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37. Receptor for advanced glycation end-products and ARDS prediction: a multicentre observational study

Author: Nathanael Eisenmann, Yvan Skrzypczak, Thierry Gillart, Thibaut Pranal, Vincent Sapin, Alexandre Lautrette, Bruno Pereira, Julien Pascal, Pauline Berthelin, Russell Chabanne, Matthieu Jabaudon, Laurence Roszyk, Bertrand Souweine, Sophie Cayot, Thomas Godet, Raiko Blondonnet, Loïc Blanchon, Jean-Michel Constantin, Corinne Belville, Jean-Sébastien Faure, CHU Clermont-Ferrand, Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Medical Biochemistry and Molecular Biology, CHU Clermont-Ferrand, Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Perioperative Medicine, CHU Clermont-Ferrand, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Unité de soins intensifs [Clermont Ferrand], CHU Clermont-Ferrand-Hôpital Gabriel Montpied, Service de Biochimie et Génétique Moléculaire [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), Service d'Anésthésie Réanimation [CHU Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], Retinoids, Development and Developmental Diseases (R2D2), Université d'Auvergne - Clermont-Ferrand I (UdA), Laboratoire de Biochimie, CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), and Jabaudon, Matthieu
Subjects: Male, ARDS, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Receptor for Advanced Glycation End Products, lcsh:Medicine, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 0302 clinical medicine, lcsh:Science, Prospective cohort study, MESH: Aged, Respiratory Distress Syndrome, education.field_of_study, Multidisciplinary, MESH: Middle Aged, MESH: Polymorphism, Single Nucleotide, Middle Aged, 3. Good health, Intensive Care Units, medicine.anatomical_structure, Cohort, Female, medicine.medical_specialty, Population, Single-nucleotide polymorphism, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Intensive care, Internal medicine, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Risk factor, education, Aged, Lung, MESH: Humans, business.industry, MESH: Receptor for Advanced Glycation End Products, lcsh:R, 030208 emergency & critical care medicine, medicine.disease, MESH: Male, 030228 respiratory system, MESH: Biomarkers, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, MESH: Respiratory Distress Syndrome, Adult, lcsh:Q, MESH: Intensive Care Units, business, MESH: Female, Biomarkers
Abstract: International audience; Acute respiratory distress syndrome (ARDS) prediction remains challenging despite available clinical scores. To assess soluble receptor for advanced glycation end-products (sRAGE), a marker of lung epithelial injury, as a predictor of ARDS in a high-risk population, adult patients with at least one ARDS risk factor upon admission to participating intensive care units (ICUs) were enrolled in a multicentre, prospective study between June 2014 and January 2015. Plasma sRAGE and endogenous secretory RAGE (esRAGE) were measured at baseline (ICU admission) and 24 hours later (day one). Four AGER candidate single nucleotide polymorphisms (SNPs) were also assayed because of previous reports of functionality (rs1800625, rs1800624, rs3134940, and rs2070600). The primary outcome was ARDS development within seven days. Of 500 patients enrolled, 464 patients were analysed, and 59 developed ARDS by day seven. Higher baseline and day one plasma sRAGE, but not esRAGE, were independently associated with increased ARDS risk. AGER SNP rs2070600 (Ser/Ser) was associated with increased ARDS risk and higher plasma sRAGE in this cohort, although confirmatory studies are needed to assess the role of AGER SNPs in ARDS prediction. These findings suggest that among at-risk ICU patients, higher plasma sRAGE may identify those who are more likely to develop ARDS. Acute respiratory distress syndrome (ARDS) still carries a high mortality rate 1,2 , and a major challenge in targeting the prevention and early treatment of ARDS is the inability to accurately predict which patients will develop the syndrome 3-6. The Lung Injury Prediction Score (LIPS) was developed to identify patients at high risk of developing ARDS; however, its positive predictive value is limited (0.14-0.23) 7. To improve prediction, one method may be to combine clinical data with plasma biomarkers that reflect the pathogenesis of ARDS such as angiopoietin-2 (Ang-2), a marker of lung endothelial injury 8. In contrast, the soluble receptor for advanced gly-cation end-products (sRAGE), a marker of lung epithelial injury 9 , may predict ARDS more accurately in selected at-risk patients, e.g. after cardiac surgery 10 , severe trauma 11 , or after major surgery 12. Soluble forms of RAGE (sRAGE) include the extracellular domain of membrane RAGE that is cleaved by proteinases 13 and endogenous secretory RAGE (esRAGE), among other forms produced by alternative splicing 14,15. sRAGE has good diagnostic value for ARDS and is associated with lung injury severity, the degree of lung epithelial injury, impaired alveolar fluid clearance, and prognosis in ARDS 16,17. Although it remains unclear whether esRAGE may be involved in ligand binding or may have any functional effects by itself, esRAGE levels were lower in the plasma and alveolar fluid from patients with ARDS than in mechanically ventilated controls without ARDS in a previous study 18. In addition, and although not yet ready for clinical use, genomic applications could facilitate better prediction
Published: 2018
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38. The long non-coding RNA HOTAIR is transcriptionally activated by HOXA9 and is an independent prognostic marker in patients with malignant glioma

Author: Xavier-Magalhães, Ana, Gonçalves, Céline, Lourenço, Tatiana, Pojo, Marta, Rocha, Miguel, Lopes, Maria, Crespo, Inês, Rebelo, Olinda, Tão, Herminio, Lima, João, Moreira, Ricardo, Pinto, Afonso, Jones, Chris, Reis, Rui, Costello, Joseph, Sousa, Nuno, Costa, Bruno, Fogli, Anne, Demattei, Marie-Véronique, Corset, Laetitia, Vaurs-Barrière, Catherine, Chautard, Emmanuel, Biau, Julian, Kemeny, Jean-Louis, Godfraind, Catherine, Pereira, Bruno, Khalil, Toufik, Grandin, Nathalie, Arnaud, Philippe, Charbonneau, Michel, Verrelle, Pierre, Life and Health Sciences Research Institute [Braga] (ICVS), University of Minho [Braga], ICVS/3B's—PT Government Associate Laboratory [Braga, Portugal], Centre of Biological Engineering [Braga, Portugal] (School of Engineering), Center for Neuroscience and Cell Biology (CNC) (CNC), University of Coimbra [Portugal] (UC)-Neuroscience Research Domain, Department of Neurosurgery [Braga, Portugal], Hospital Escala Braga [Braga, Portugal], Divisions of molecular pathology and cancer therapeutics [Surrey, UK], The institute of cancer research [London], Molecular Oncology Research Center [São Paulo, Brazil], Barretos Cancer Hospital [São Paulo, Brazil], Department of Neurological Surgery [San Francisco, CA, USA] (School of Medicine), University of California [San Francisco] (UCSF), University of California-University of California, Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Biochimie et Génétique Moléculaire [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Cancer Resistance Exploring and Targeting (CREaT), Université d'Auvergne - Clermont-Ferrand I (UdA), Laboratoire de Neuropathologie, Université Catholique de Louvain = Catholic University of Louvain (UCL)-Clinique Saint-Luc, Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service de Neurochirurgie A [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], Université de Lorraine (UL), Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Fundação Para A Ciência e Tecnologia (PTDC/SAU-GMG/113795/2009, SFRH/BPD/33612/2009 and IF/00601/2012 to B.M.C., SFRH//88220/2012 to A.X.M., SFRH/BD/92786/2013 to C.S.G, SFRH/BD/81042/2011 to M.P., and SFRH/BD/51996/2012 to T.L.), Project cofinanced by Programa Operacional Regional do Norte (ON.2 – O Novo Norte), Quadro de Referência Estratégico Nacional (QREN), Fundo Europeu de Desenvolvimento Regional (FEDER), Fundação Calouste Gulbenkian (B.M.C.), and Liga Portuguesa Contra o Cancro, Portugal (B.M.C.). This article has been developed under the scope of the projects NORTE-01-0246-FEDER-000012, NORTE-01-0145-FEDER-000023 and NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). This work has been funded by FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI-01-0145-FEDER-007038. C.J. acknowledges NHS funding to the Biomedical Research Centre. P.A. acknowledges the Plan Cancer-INSERM (CS14085CS‘Gliobiv’, PA), the Cancéropole CLARA (Oncostarter «Gliohoxas», PA), Fonds de dotation Patrick Brou de Lauriére (PA)., Université de Tours (UT), University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Arnaud, Philippe, Universidade do Minho, and Service de Neurochirurgie [CHU Clermont-Ferrand]
Subjects: 0301 basic medicine, Molecular Networks (q-bio.MN), Oncology and Carcinogenesis, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, 03 medical and health sciences, chemistry.chemical_compound, Rare Diseases, HOTAIR, [SDV.CAN] Life Sciences [q-bio]/Cancer, Glioma, glioma, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Genetics, 2.1 Biological and endogenous factors, Quantitative Biology - Genomics, Quantitative Biology - Molecular Networks, Aetiology, Gene, Cancer, Genomics (q-bio.GN), Human Genome, Neurosciences, glioblastoma, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], Methylation, HOXA9, medicine.disease, Long non-coding RNA, 3. Good health, Demethylating agent, Brain Disorders, Brain Cancer, 030104 developmental biology, Oncology, chemistry, [SDV.BBM.MN] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], FOS: Biological sciences, DNA methylation, Cancer research, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], prognosis, Chromatin immunoprecipitation, Research Paper
Abstract: The lncRNA HOTAIR has been implicated in several human cancers. Here, we evaluated the molecular alterations and upstream regulatory mechanisms of HOTAIR in glioma, the most common primary brain tumors, and its clinical relevance. HOTAIR gene expression, methylation, copy-number and prognostic value were investigated in human gliomas integrating data from online datasets and our cohorts. High levels of HOTAIR were associated with higher grades of glioma, particularly IDH wild-type cases. Mechanistically, HOTAIR was overexpressed in a gene dosage-independent manner, while DNA methylation levels of particular CpGs in HOTAIR locus were associated with HOTAIR expression levels in GBM clinical specimens and cell lines. Concordantly, the demethylating agent 5-Aza-2'-deoxycytidine affected HOTAIR transcriptional levels in a cell line-dependent manner. Importantly, HOTAIR was frequently co-expressed with HOXA9 in high-grade gliomas from TCGA, Oncomine, and our Portuguese and French datasets. Integrated in silico analyses, chromatin immunoprecipitation, and qPCR data showed that HOXA9 binds directly to the promoter of HOTAIR. Clinically, GBM patients with high HOTAIR expression had a significantly reduced overall survival, independently of other prognostic variables. In summary, this work reveals HOXA9 as a novel direct regulator of HOTAIR, and establishes HOTAIR as an independent prognostic marker, providing new therapeutic opportunities to treat this highly aggressive cancer., Fundação Para A Ciência e Tecnologia (PTDC/ SAU-GMG/113795/2009; SFRH/BPD/33612/2009 and IF/00601/2012 to B.M.C.; SFRH/BD/88220/2012 to A.X.M.; SFRH/BD/92786/2013 to C.S.G; SFRH/BD/81042/2011 to M.P.; and SFRH/BD/51996/2012 to T.L.), Project co-financed by Programa Operacional Regional do Norte (ON.2 – O Novo Norte), Quadro de Referência Estratégico Nacional (QREN), Fundo Europeu de Desenvolvimento Regional (FEDER); Fundação Calouste Gulbenkian (B.M.C.); and Liga Portuguesa Contra o Cancro, Portugal (B.M.C.). This article has been developed under the scope of the projects NORTE-01-0246-FEDER-000012, NORTE-01-0145-FEDER-000023 and NORTE-01-0145FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). This work has been funded by FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI01-0145-FEDER-007038. C.J. acknowledges NHS funding to the Biomedical Research Centre. P.A. acknowledges the Plan Cancer-INSERM (CS14085CS‘Gliobiv’, PA), the Cancéropole CLARA (Oncostarter «Gliohoxas»; PA), Fonds de dotation Patrick Brou de Lauriére (PA)., info:eu-repo/semantics/publishedVersion
Published: 2018
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39. Stability of an ophthalmic formulation of polyhexamethylene biguanide in gamma-sterilized and ethylene oxide sterilized low density polyethylene multidose eyedroppers

Author: Yassine Bouattour, Valérie Sautou, Mireille Jouannet, Philip Chennell, Mathieu Wasiak, Service Pharmacie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Louise Michel [Clermont-Ferrand], CHU Clermont-Ferrand, Institut de Chimie de Clermont-Ferrand (ICCF), SIGMA Clermont (SIGMA Clermont)-Institut de Chimie du CNRS (INC)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), CHU Louise Michel [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], and CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand]
Subjects: Drugs and Devices, medicine.drug_class, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Liquid chromatography, Ophthalmic solution, lcsh:Medicine, 02 engineering and technology, Pharmaceutical technology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Chromatography detector, medicine, Acanthamoeba keratitis, Chromatography, Ethylene oxide, Biguanide, General Neuroscience, lcsh:R, Eye drop, General Medicine, Polyethylene, 021001 nanoscience & nanotechnology, medicine.disease, Polyhexamethylene biguanide, Ophthalmology, Low-density polyethylene, chemistry, 030221 ophthalmology & optometry, Particle size, Low density polyethylene eye droppers, 0210 nano-technology, General Agricultural and Biological Sciences, Drug stability
Abstract: Background Polyhexamethylene biguanide (PHMB) eye drops are a frequently used medication to treat Acanthamoeba keratitis. In the absence of marketed PHMB eye drops, pharmacy-compounding units are needed to prepare this much needed treatment, but the lack of validated PHMB stability data severely limits their conservation by imposing short expiration dates after preparation. In this study we aim to assess the physicochemical and microbiological stability of a 0.2 mg/mL PHMB eye drop formulation stored in two kinds of polyethylene bottles at two different temperatures. Methods A liquid chromatography coupled with diode array detector stability-indicating method was validated to quantify PHMB, using a cyanopropyl bonded phase (Agilent Zorbax Eclipse XDB-CN column 4.6 × 75 mm with particle size of 3.5 μm) and isocratic elution consisting of acetonitrile/deionized water (3/97 v/v) at a flow rate of 1.3 mL/min. PHMB eye drops stability was assessed for 90 days of storage at 5 and 25 °C in ethylene oxide sterilized low density polyethylene (EOS-LDPE) and gamma sterilized low density polyethylene (GS-LDPE) bottles. The following analyses were performed: visual inspection, PHMB quantification and breakdown products (BPs) screening, osmolality and pH measurements, and sterility assessment. PHMB quantification and BP screening was also performed on the drops emitted from the multidose eyedroppers to simulate in-use condition. Results The analytical method developed meets all the qualitative and quantitative criteria for validation with an acceptable accuracy and good linearity, and is stability indicating. During 90 days of storage, no significant decrease of PHMB concentration was found compared to initial concentration in all stored PHMB eye drops. However, BP were found at day 30 and at day 90 of monitoring in both kind of bottles, stored at 5 and 25 °C, respectively. Although no significant variation of osmolality was found and sterility was maintained during 90 days of monitoring, a significant decrease of pH in GS-LDPE PHMB eye drops was noticed reaching 4 and 4.6 at 25 °C and 5 °C respectively, compared to initial pH of 6.16. Discussion Although no significant decrease in PHMB concentration was found during 90 days of monitoring in all conditions, the appearance of BPs and their unknown toxicities let us believe that 0.2 mg/mL PHMB solution should be conserved for no longer than 60 days in EOS-LDPE bottles at 25 °C.
Published: 2018
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40. Rationale, study design and analysis plan of the lung imaging morphology for ventilator settings in acute respiratory distress syndrome study (LIVE study): Study protocol for a randomised controlled trial

Author: Jean-Michel Constantin, Bruno Pereira, Emmanuel Futier, Thomas Godet, Vincent Sapin, Jean-Etienne Bazin, Matthieu Jabaudon, Laurence Roszyk, CHU Clermont-Ferrand, Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Service d'Anésthésie Réanimation [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Laboratoire de Biochimie, Service de Biochimie et Génétique Moléculaire [CHU Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), CHU Gabriel Montpied [Clermont-Ferrand], and CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand]
Subjects: Male, ARDS, medicine.medical_treatment, Kaplan-Meier Estimate, Critical Care and Intensive Care Medicine, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, law.invention, Positive-Pressure Respiration, 0302 clinical medicine, Randomized controlled trial, Quality of life, law, 030212 general & internal medicine, Hospital Mortality, Lung, Randomized Controlled Trials as Topic, Ultrasonography, Respiratory Distress Syndrome, General Medicine, respiratory system, Middle Aged, 3. Good health, Prone position, Treatment Outcome, Research Design, Breathing, Female, Adult, medicine.medical_specialty, 03 medical and health sciences, medicine, Prone Position, Tidal Volume, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Intensive care medicine, Aged, Mechanical ventilation, Ventilators, Mechanical, business.industry, Body Weight, medicine.disease, Respiration, Artificial, Clinical trial, Oxygen, Pneumonia, Anesthesiology and Pain Medicine, 030228 respiratory system, Emergency medicine, business, Tomography, X-Ray Computed
Abstract: Different acute respiratory distress syndrome (ARDS) phenotypes may explain controversial results in clinical trials. Lung-morphology is one of the ARDS-phenotypes and physiological studies suggest different responses in terms of positive-end-expiratory-pressure (PEEP) and recruitment-manoeuvres (RM) according to loss of aeration. To evaluate whether tailored ventilator regimens may impact ARDS outcomes, our group has designed a randomised-clinical-trial of ventilator settings according to lung morphology in moderate-to-severe ARDS (LIVE study). Method Patients will be enrolled within the first 12 hours of ARDS onset. In both groups, volume-controlled ventilation with low tidal-volumes (Vt) will be used to target a plateau pressure ≤ 30 cmH 2 O. In the control group, the PEEP level and inspired fraction of oxygen (FiO 2 ) will be set using the ARDSNet table; a Vt of 6 mL/kg of predicted body weight (PBW) will be set and prone position (PP) will be applied. In the intervention arm, the ventilator will be set according to lung morphology (focal/non-focal) that will be assessed according to CT-scan ± chest x-ray + lung echography. For focal ARDS patients, a Vt of 8 mL/kg PBW will be used along with low PEEP and PP. For non-focal ARDS patients, a Vt of 6 mL/kg PBW will be used with RM and PEEP to reach a plateau pressure ≤ 30 cmH 2 O. The primary outcome is all-cause 90-day mortality and the secondary outcomes are: in-hospital mortality, mortality at day 28, 60, 180 and 365; ventilator-free days at day 30, quality of life at one year; ventilator-associated pneumonia rate; barotrauma; ICU and hospital length of stay. This RCT is registered on Clinicaltrials.gov under identifier NCT02149589 .
Published: 2017
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41. Detection of the alternative lengthening of telomeres pathway in malignant gliomas for improved molecular diagnosis

Author: Bruno Pereira, Marie-Véronique Demattei, Pierre Verrelle, Jean-Louis Kemeny, Anne Fogli, Julian Biau, Nathalie Grandin, Philippe Arnaud, Emmanuel Chautard, Laetitia Corset, Catherine Godfraind, Michel Charbonneau, Catherine Vaurs-Barrière, T. Khalil, Service de Biochimie et Génétique Moléculaire [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Génétique, immunothérapie, chimie et cancer (GICC), UMR 7292 CNRS [2012-2017] (GICC UMR 7292 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Cancer Resistance Exploring and Targeting (CREaT), Université d'Auvergne - Clermont-Ferrand I (UdA), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Laboratoire de pathologie, Laboratoire de Neuropathologie, Université Catholique de Louvain = Catholic University of Louvain (UCL)-Clinique Saint-Luc, Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service de Neurochirurgie [CHU Clermont-Ferrand], Image Guided Clinical Neurosciences and Connectomics (IGCNC), Génétique, Reproduction et Développement (GReD), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Etude des Parasites Génétiques (LEPG), Université de Tours, Université de Tours-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement - Clermont Auvergne (GReD ), Thérapie ciblée combinatoire en Onco-Hématologie (EA3846), Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), service d’anatomopathologie, Centre Hospitalier Universitaire Gabriel Montpied, Laboratoire de Pathologie, Université Catholique de Louvain (UCL)-Clinique Saint-Luc, Délégation à la Recherche Clinique et à l’Innovation, Centre Hospitalier Universitaire de Clermont-Ferrand, Service de Neurochirurgie A [Clermont-Ferrand], CHU Clermont-Ferrand-Hôpital Gabriel Montpied, 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), Centre Jean Perrin, CRLCC Jean Perrin, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Service de Biochimie Médicale et Biologie Moléculaire [CHU Clermont-Ferrand], Génétique, Reproduction et Développement - Clermont Auvergne ( GReD ), IFR79-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Clermont Auvergne ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), UMR 6239, Equipe Cellules usine, Ingénierie des protéines et Bio-informatique, Université Francois Rabelais [Tours]-Centre National de la Recherche Scientifique ( CNRS ), Génétique, Immunothérapie, Chimie et Cancer ( GICC ), Université de Tours-Centre National de la Recherche Scientifique ( CNRS ), Cancer Resistance Exploring and Targeting ( CREaT ), Université d'Auvergne - Clermont-Ferrand I ( UdA ), Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne ( IMoST ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Clermont Auvergne ( UCA ), Université Catholique de Louvain ( UCL ) -Clinique Saint-Luc, Biostat Unit, Image Guided Clinical Neurosciences and Connectomics ( IGCNC ), Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), and CHAUTARD, Emmanuel
Subjects: 0301 basic medicine, Male, Cancer Research, Telomerase, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], medicine.disease_cause, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Cohort Studies, Exon, chemistry.chemical_compound, DNA Modification Methylases, ComputingMilieux_MISCELLANEOUS, Mutation, Brain Neoplasms, Brain, Methylation, Glioma, Middle Aged, Isocitrate Dehydrogenase, 3. Good health, Neurology, Oncology, [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Female, Adult, X-linked Nuclear Protein, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Extrachromosomal DNA, Cell Line, Tumor, medicine, Humans, ATRX, Tumor Suppressor Proteins, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Telomere Homeostasis, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Molecular biology, Telomere, 030104 developmental biology, DNA Repair Enzymes, chemistry, RNA, Neurology (clinical), Neoplasm Grading, DNA
Abstract: International audience; Human malignant gliomas exhibit acquisition of either one of two telomere maintenance mechanisms, resulting from either reactivation of telomerase expression or activation of an alternative lengthening of telomeres (ALT) mechanism. In the present study, we analyzed 63 human malignant gliomas for the presence of ALT-specific extrachromosomal circles of telomeric DNA (C-circles) and measured telomerase expression, telomeric DNA content (Telo/Alu method), and telomeric repeat-containing RNAs (TERRA) levels. We also assessed histomolecular markers routinely used in clinical practice. The presence of C-circles significantly correlated with IDH1/2 mutation, MGMT exon 1 methylation, low Ki-67 immunostaining, increased telomeric DNA content, absence of functional ATRX protein and level of HTERT gene expression. In multivariate analysis, we observed a trend to a correlation between elevated TERRA levels and increased survival. Interestingly, the C-circles assay allowed to detect ALT activation in glioblastomas exhibiting wild-type IDH1/2 and ATRX expression. These results suggest that, after the correlations uncovered here have been confirmed on larger numbers of tumors, telomeric markers might be useful in improving diagnosis. They also point out to the utility of using the specific, sensitive and quantitative C-circle and Telo/Alu assays that can work with as few as 30 ng of tumor DNA
Published: 2017
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42. Neuronal activity correlated with checking behaviour in the subthalamic nucleus of patients with obsessive–compulsive disorder

Author: Burbaud, Pierre, Clair, Anne-Hélène, Langbour, Nicolas, Fernandez-Vidal, Sara, Goillandeau, Michel, Michelet, Thomas, Bardinet, Eric, Chéreau, Isabelle, Durif, Franck, Polosan, Mircea, Chabardès, Stephan, Fontaine, Denys, Magnié-Mauro, Marie-Noelle, Houeto, Jean-Luc, Bataille, Benoît, Millet, Bruno, Vérin, Marc, Baup, Nicolas, Krebs, Marie-Odile, Cornu, Philippe, Pelissolo, Antoine, Arbus, Christophe, Simonetta-Moreau, Marion, Yelnik, Jérôme, Welter, Marie-Laure, Mallet, Luc, Renseigné, Non, Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), 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)-CHU Pitié-Salpêtrière [APHP], Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), 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 psychiatrie, CHU Clermont-Ferrand, NS-Park/FCRIN Network, UMS 015, Neurology service hôpital Gabriel Montpied, Hôpital Gabriel Montpied, ANTE-INSERM U836, équipe 11, Fonctions cérébrales et neuromodulation, 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), CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Laboratoire de psychologie cognitive et sociale (LPCS), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), Service de neurologie [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Université de Poitiers, Service de Psychiatrie adulte [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], 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), Service de neurologie [Rennes], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Hôpital Sainte-Anne, Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, INSERM U955, équipe 15, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Hôpital Albert Chenevier-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Hôpital Albert Chenevier-Réseau de coopération scientifique en santé mentale, Fondation FondaMental [Créteil]-Fondation FondaMental [Créteil]-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'anatomie et cytologie pathologiques [Purpan], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Imagerie cérébrale et handicaps neurologiques, Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-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)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-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)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [APHP], Oxalya, The Programme Hospitalier de la Recherche Clinique Assistance Publique–Hôpitaux de Paris - AOM 03141, Agence Nationale pour la Recherche, The French STOC Study Group, Physiologie et physiopathologie de la signalisation cellulaire (PPSC), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux]-Centre National de la Recherche Scientifique (CNRS), Laboratoire Mouvement Adaptation Cognition (MAC), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Center for NeuroImaging Research-Human MRI Neuroimaging core facility for clinical research [ICM Paris] (CENIR), 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)-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), Equipe NEMESIS - Centre de Recherches de l'Institut du Cerveau et de la Moelle épinière (NEMESIS-CRICM), 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)-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 Neurologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], Service de Psychiatrie, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurochirurgie, Centre Hospitalier Universitaire de Nice (CHU Nice), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), 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]-Hôpital Guillaume Régnier, Service de Neurologie [Rennes] = Neurology [Rennes], CHU Pontchaillou [Rennes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Hôpital Sainte-Anne, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service Anatomie et cytologie pathologiques [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Imagerie cérébrale et handicaps neurologiques (ICHN), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-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), CIC AP-HP (pitie-Salpetriere)/inserm, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), The Programme Hospitalier de la Recherche Clinique Assistance Publique–Hôpitaux de Paris - AOM 03141, Agence Nationale pour la Recherche ANR-05-JCJC-0235-01, ANR-06-NEURO-006-01, ANR-05-JCJC-0235,GB comportement,Comportements répétitifs pathologiques et troubles émotionnels liés au dysfonctionnement des ganglions de la base : physiopathologie et innovation thérapeutique.(2005), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux]-Centre National de la Recherche Scientifique (CNRS), 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), Centre de Neuro-Imagerie de Recherche (CENIR), 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)-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), Département de Neurologie A, CHU Clermont-Ferrand-Hôpital Gabriel Montpied, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-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), Service de Neurologie [Rennes], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Service de Neurochirurgie [CHU Pitié-Salpêtrière], Service de psychiatrie adulte [CHU Pitié-Salpêtière], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Département de Neurologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-IFR70-CHU Pitié-Salpêtrière [APHP], Physiologie et physiopathologie de la signalisation cellulaire ( PPSC ), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux]-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire Mouvement Adaptation Cognition ( MAC ), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière ( CRICM ), 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 ), Centre de Neuro-Imagerie de Recherche ( CENIR ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Equipe NEMESIS - Centre de Recherches de l'Institut du Cerveau et de la Moelle épinière ( NEMESIS-CRICM ), 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 ) -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 ), Grenoble Institut des Neurosciences ( GIN ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHU Nice, Université de Poitiers-Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Comportement et noyaux gris centraux [Rennes], Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Université européenne de Bretagne ( UEB ) -CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Hôpital Sainte-Anne, Service de psychiatrie adulte, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-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 ), Assistance publique - Hôpitaux de Paris (AP-HP)-IFR70-Hôpital de la Salpétrière, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM), Pollak, Pierre, Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), 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), Institut des Maladies Neurodégénératives [Bordeaux] ( IMN ), Université de Bordeaux ( UB ) -Centre National de la Recherche Scientifique ( CNRS ), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute ( ICM ), 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 ) -CHU Pitié-Salpêtrière [APHP], Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble, Laboratoire de Physique des Plasmas ( LPP ), Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Saclay-PSL Research University ( PSL ) -Sorbonne Universités-École polytechnique ( X ) -Observatoire de Paris-Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris-Sud - Paris 11 ( UP11 ), Laboratoire de psychologie cognitive et sociale ( LPCS ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ), Charite-Universitatsmedizin Berlin [Berlin], Institut des Sciences et Technologies de l'Information de Troyes ( ISTIT ), Université de Technologie de Troyes ( UTT ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier-Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier-Réseau de coopération scientifique en santé mentale, Fondation FondaMental [Créteil]-Fondation FondaMental [Créteil]-Institut Mondor de Recherche Biomédicale ( IMRB ), and Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 )
Subjects: Adult, Male, Obsessive-Compulsive Disorder, Deep brain stimulation, OCD pathophysiology, Obsessive-Compulsive Disorder/physiopathology/psychology, medicine.medical_treatment, Compulsive Behavior/physiopathology/psychology, 03 medical and health sciences, 0302 clinical medicine, Obsessive compulsive, Basal ganglia, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, medicine, Humans, Premovement neuronal activity, In patient, doubt-related neuronal activity, Subthalamic Nucleus/physiopathology, deep brain stimulation in OCD, 030304 developmental biology, Neurons, subthalamic nucleus, 0303 health sciences, [ INFO.INFO-IM ] Computer Science [cs]/Medical Imaging, [SCCO.NEUR]Cognitive science/Neuroscience, Cognition, Middle Aged, ddc:616.8, Subthalamic nucleus, checking task, Compulsive behavior, [ SCCO.NEUR ] Cognitive science/Neuroscience, Compulsive Behavior, Female, Neurology (clinical), medicine.symptom, Psychology, Neurons/physiology, Neuroscience, 030217 neurology & neurosurgery
Abstract: International audience; Doubt, and its behavioural correlate, checking, is a normal phenomenon of human cognition that is dramatically exacerbated in obsessive-compulsive disorder. We recently showed that deep brain stimulation in the associative-limbic area of the subthalamic nucleus, a central core of the basal ganglia, improved obsessive-compulsive disorder. To understand the physiological bases of symptoms in such patients, we recorded the activity of individual neurons in the therapeutic target during surgery while subjects performed a cognitive task that gave them the possibility of unrestricted repetitive checking after they had made a choice. We postulated that the activity of neurons in this region could be influenced by doubt and checking behaviour. Among the 63/87 task-related neurons recorded in 10 patients, 60% responded to various combinations of instructions, delay, movement or feedback, thus highlighting their role in the integration of different types of information. In addition, task-related activity directed towards decision-making increased during trials with checking in comparison with those without checking. These results suggest that the associative-limbic subthalamic nucleus plays a role in doubt-related repetitive thoughts. Overall, our results not only provide new insight into the role of the subthalamic nucleus in human cognition but also support the fact that subthalamic nucleus modulation by deep brain stimulation reduced compulsive behaviour in patients with obsessive-compulsive disorder.
Published: 2013
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43. A novel assistive method for rigidity evaluation during deep brain stimulation surgery using acceleration sensors

Author: Erik Schkommodau, Jean-Jacques Lemaire, Philippe Derost, Ashesh Shah, Jerome Coste, Raphael Guzman, Ethan Taub, Simone Hemm, Institute for Medical and Analytical Technologies, School of Life Sciences (IMA), University of Applied Sciences and Arts Northwestern Switzerland (FHNW), Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Service de Neurochirurgie [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Departments of Neurosurgery and Biomedicine, University Hospital Basel [Basel], Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Service de Neurologie [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU de Clermont-Ferrand, Université Clermont Auvergne, Institut Pascal, Apport de l'accélérométrie à la stimulation cérébrale - 2011-A00774-37 - CHU de Clermont-Ferrand, Thérapie guidée par l'image (TGI), SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), This research was funded by the Swiss National Science Foundation as a part of the project205321_135285 and partly by the Germaine de Stael program of the Swiss Academy ofEngineering Sciences. We acknowledge and thank Prof. F. Durif, Dr. M. Ulla, and Dr. A.Marques of the Department of Neurology at the CHU Clermont-Ferrand, France, and Ms. BiancaRaffaelli and Prof. Dr. Peter Fuhr of the Department of Neurology at the University Hospital ofBasel, Switzerland, for performing the routine passive movements for rigidity evaluations.The clinical use of the afore-described data-recording system for the purpose of intraoperativeand postoperative symptom evaluation in the framework of this study was approved by theinstitutional review boards of the University Hospital in Clermont-Ferrand (France) and theUniversity Hospital of Basel (Switzerland)., CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], 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), Service de Neurochirurgie [CHU Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, and SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS)
Subjects: medicine.medical_specialty, Deep brain stimulation, Movement disorders, Parkinson's disease, medicine.medical_treatment, fields of Forel, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Deep Brain Stimulation, Movement, 0206 medical engineering, Stimulation, Rigidity (psychology), 02 engineering and technology, Wrist, Accelerometer, Neurosurgical Procedures, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, medicine, Humans, Electrodes, functional neurosurgery, Aged, subthalamic nucleus, business.industry, Parkinson Disease, General Medicine, Middle Aged, medicine.disease, 020601 biomedical engineering, quantification, Muscle Rigidity, Subthalamic nucleus, medicine.anatomical_structure, rigidity, Physical therapy, acceleration sensor, intraoperative, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.IB]Life Sciences [q-bio]/Bioengineering, medicine.symptom, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: OBJECTIVEDespite the widespread use of deep brain stimulation (DBS) for movement disorders such as Parkinson's disease (PD), the exact anatomical target responsible for the therapeutic effect is still a subject of research. Intraoperative stimulation tests by experts consist of performing passive movements of the patient's arm or wrist while the amplitude of the stimulation current is increased. At each position, the amplitude that best alleviates rigidity is identified. Intrarater and interrater variations due to the subjective and semiquantitative nature of such evaluations have been reported. The aim of the present study was to evaluate the use of an acceleration sensor attached to the evaluator's wrist to assess the change in rigidity, hypothesizing that such a change will alter the speed of the passive movements. Furthermore, the combined analysis of such quantitative results with anatomy would generate a more reproducible description of the most effective stimulation sites.METHODSTo test the reliability of the method, it was applied during postoperative follow-up examinations of 3 patients. To study the feasibility of intraoperative use, it was used during 9 bilateral DBS operations in patients suffering from PD. Changes in rigidity were calculated by extracting relevant outcome measures from the accelerometer data. These values were used to identify rigidity-suppressing stimulation current amplitudes, which were statistically compared with the amplitudes identified by the neurologist. Positions for the chronic DBS lead implantation that would have been chosen based on the acceleration data were compared with clinical choices. The data were also analyzed with respect to the anatomical location of the stimulating electrode.RESULTSOutcome measures extracted from the accelerometer data were reproducible for the same evaluator, thus providing a reliable assessment of rigidity changes during intraoperative stimulation tests. Of the 188 stimulation sites analyzed, the number of sites where rigidity-suppressing amplitudes were found increased from 144 to 170 when the accelerometer evaluations were considered. In general, rigidity release could be observed at significantly lower amplitudes with accelerometer evaluation (mean 0.9 ± 0.6 mA) than with subjective evaluation (mean 1.4 ± 0.6 mA) (p < 0.001). Of 14 choices for the implant location of the DBS lead, only 2 were the same for acceleration-based and subjective evaluations. The comparison across anatomical locations showed that stimulation in the fields of Forel ameliorates rigidity at similar amplitudes as stimulation in the subthalamic nucleus, but with fewer side effects.CONCLUSIONSThis article describes and validates a new assistive method for assessing rigidity with acceleration sensors during intraoperative stimulation tests in DBS procedures. The initial results indicate that the proposed method may be a clinically useful aid for optimal DBS lead placement as well as a new tool in the ongoing scientific search for the optimal DBS target for PD.
Published: 2016
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44. Hallucinations in schizophrenia and Parkinson's disease: an analysis of ă sensory modalities involved and the repercussion on patients

Author: Ana Marques, Miguel Ulla, A.M. Tronche, I. de Chazeron, C. Lançon, G. Fénelon, Georges Brousse, Philippe Derost, Bruno Pereira, David Misdrahi, Isabelle Chéreau-Boudet, Renaud Jardri, Pierre-Michel Llorca, F. Durif, Raymund Schwan, B. Debilly, University Institute for Intelligent Systems and Numerical Applications in Engineering, University of Las Palmas de Gran Canaria (ULPGC), Laboratoire Sciences Cognitives et Sciences Affectives - UMR 9193 (SCALab), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Centre d'Ingéniérie Hydraulique, EDF (EDF), Santé Publique et maladies Chroniques : Qualité de vie Concepts, Usages et Limites, Déterminants (SPMC), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM), Service de Neurologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Laboratoire de Neurosciences Fonctionnelles et Pathologies (LNFP), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], Service de neurologie, Hôpital Gabriel Montpied, Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Hospitalier Universitaire de France, Sciences Cognitives et Sciences Affectives (SCALab) - UMR 9193 (SCALab), Fondation FondaMental [Créteil], Université de Lille, CNRS, CHU Lille, Université d'Auvergne - Clermont-Ferrand I [UdA], Laboratoire Sciences Cognitives et Sciences Affectives - UMR 9193 [SCALab], Institut de Neurosciences cognitives et intégratives d'Aquitaine [INCIA], Centre hospitalier Charles Perrens [Bordeaux], École normale supérieure - Paris [ENS-PSL], Institut Mondor de Recherche Biomédicale [IMRB], Centre Hospitalier Régional Universitaire de Nancy [CHRU Nancy], Hôpital Sainte-Marguerite [CHU - APHM] [Hôpitaux Sud ], Santé Publique et maladies Chroniques : Qualité de vie Concepts, Usages et Limites, Déterminants [SPMC], and Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux [NPsy-Sydo]
Subjects: Adult, Disease specific, medicine.medical_specialty, Parkinson's disease, Hallucinations, [SHS.PSY]Humanities and Social Sciences/Psychology, Disease, Audiology, behavioral disciplines and activities, Article, [SHS]Humanities and Social Sciences, 03 medical and health sciences, [SCCO]Cognitive science, 0302 clinical medicine, Stimulus modality, mental disorders, medicine, Humans, Psychiatry, ComputingMilieux_MISCELLANEOUS, Aged, Multidisciplinary, Modalities, business.industry, Parkinson Disease, Middle Aged, Guardian angel, medicine.disease, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, Visual Hallucination, 030227 psychiatry, Hallucinating, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Schizophrenia, Quality of Life, business, 030217 neurology & neurosurgery
Abstract: Hallucinations have been described in various clinical populations, but they are neither disorder nor disease specific. In schizophrenia patients, hallucinations are hallmark symptoms and auditory ones are described as the more frequent. In Parkinson’s disease, the descriptions of hallucination modalities are sparse, but the hallucinations do tend to have less negative consequences. Our study aims to explore the phenomenology of hallucinations in both hallucinating schizophrenia patients and Parkinson’s disease patients using the Psycho-Sensory hAllucinations Scale (PSAS). The main objective is to describe the phenomena of these clinical symptoms in those two specific populations. Each hallucinatory sensory modality significantly differed between Parkinson’s disease and schizophrenia patients. Auditory, olfactory/gustatory and cœnesthetic hallucinations were more frequent in schizophrenia than visual hallucinations. The guardian angel item, usually not explored in schizophrenia, was described by 46% of these patients. The combination of auditory and visual hallucinations was the most frequent for both Parkinson’s disease and schizophrenia. The repercussion index summing characteristics of each hallucination (frequency, duration, negative aspects, conviction, impact, control and sound intensity) was always higher for schizophrenia. A broader view including widespread characteristics and interdisciplinary works must be encouraged to better understand the complexity of the process involved in hallucinations.
Published: 2016
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45. Improving Peripheral and Central Vascular Adjustments during Exercise through a Training Program in Adolescents with Obesity

Author: Valérie Julian, Bruno Pereira, Frédéric Costes, Martine Duclos, David Thivel, Ruddy Richard, Médecine du Sport et Explorations Fonctionnelles, CHU Clermont-Ferrand, Département de Pédiatrie, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Biostatistics Unit (Department of Clinical Research and Innovation), Service Médecine du Sport et Explorations Fonctionnelles [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], Service de Pédiatrie Générale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques (AME2P), UFR Sciences et Techniques des Activités Physiques et Sportives - Clermont-Ferrand (UFR STAPS - UBP), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP), Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), Centre Hospitalier Universitaire de Clermont-Ferrand, Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), and Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Institut National de la Recherche Agronomique (INRA)
Subjects: Male, Pediatric Obesity, Health (social science), [SDV]Life Sciences [q-bio], Treatment outcome, physical activity, Quadriceps Muscle, activité physique, 0302 clinical medicine, physical exercise, insulin resistance, Cardiac Output, lcsh:RC620-627, Exercise Tolerance, Spectroscopy, Near-Infrared, exercise, vascularisation, muscle squelettique, Adaptation, Physiological, insulino- résistance, Peripheral, Exercise Therapy, lcsh:Nutritional diseases. Deficiency diseases, Treatment Outcome, Alimentation et Nutrition, Female, Original Article, Training program, lcsh:Nutrition. Foods and food supply, childhood obesity, microvasculature, medicine.medical_specialty, 030209 endocrinology & metabolism, lcsh:TX341-641, Childhood obesity, 03 medical and health sciences, Physical medicine and rehabilitation, Insulin resistance, Oxygen Consumption, vascularization, 030225 pediatrics, Physiology (medical), medicine, Food and Nutrition, Humans, obésité infantile, Exercise physiology, business.industry, medicine.disease, Obesity, Clinical trial, voluntary muscle, adolescent, Microvessels, Physical therapy, spectroscopie infra rouge, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: Objective: The effects of a training program (TP) on muscle microvascularization during exercise remained to be explored in adolescents with obesity. We hypothesized that a TP would lead to better microvascular adaptations to exercise in skeletal muscle. Methods: 15 inactive adolescents followed a 12-week TP where both peripheral (muscular microvascularization) and central (cardiac) adaptations to exercise (40 min exercise set at 70% V̇O2peak) were assessed before and after intervention. Microvascular adaptations were evaluated in the Musculus vastus lateralis with near-infrared spectroscopy, by measurement of muscular blood volume (IR-BV) and tissue oxygen saturation (IR-SO2). Central adaptations were evaluated using thoracic impedance. Results: The TP favored lower BMI (p < 0.001), lower total and abdominal fat (p < 0.001), and a trend for the decrease in insulin resistance index (p = 0.07). V̇O2peak relative to weight (p = 0.008) and maximum power output increased (p = 0.0003). A smaller initial drop in IR-BV and IR-SO2 (p < 0.001), a prompter return of these parameters to their base values, and a higher IR-BV and IR-SO2 all times taken together (p < 0.001) were observed after completing the TP. Concerning central adaptation, cardiac output decreased (p < 0.001). Conclusion: We demonstrate for the first time by noninvasive techniques that a training program induces peripheral and central vascular adaptations to exercise in adolescents with obesity.
Published: 2016
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46. Impact of Mood and Behavioral Disorders on Quality of Life in Parkinson's disease

Author: Franck Durif, Isabelle Chereau, Isabelle Rieu, Christine Brefel-Courbon, Ingrid de Chazeron, Paul Krack, Fabienne Ory-Magne, Miguel Ulla, Bruno Pereira, Kathy Dujardin, Jean-Luc Houeto, Amélie Bichon, François Tison, Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Service de Neurochirurgie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service de psychiatrie, CHU Clermont-Ferrand, Service de Neurologie [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], 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], Centre d'investigation clinique de Toulouse (CIC 1436), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Neurology, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Grenoble Institut des Neurosciences (GIN), 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)-Sorbonne Université (SU), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], 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), 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), Département de neurologie [Lille], [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), and Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Subjects: Quality of life, 0301 basic medicine, Male, medicine.medical_specialty, Parkinson's disease, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Disease, Affect (psychology), 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Mood Disorders/etiology/*psychology, medicine, Humans, Psychiatry, ComputingMilieux_MISCELLANEOUS, Depression (differential diagnoses), Aged, Quality of Life/*psychology, Parkinson Disease/*psychology, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Mood Disorders, [SCCO.NEUR]Cognitive science/Neuroscience, Mental Disorders, Mental Disorders/etiology/*psychology, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Impulse control disorders, Parkinson Disease, Middle Aged, medicine.disease, ddc:616.8, 030104 developmental biology, Mood, Mood disorders, Quality of Life, Anxiety, Female, Neurology (clinical), medicine.symptom, Psychology, 030217 neurology & neurosurgery
Abstract: Background Mood symptoms negatively affect quality of life of Parkinson's disease (PD); however little is known about the impact of behavioral disorders such as impulse control disorders, and non-motor fluctuations on quality of life. Objective To assess the impact of mood and behavioral disorders on quality of life in PD. Methods 136 (84% male) PD were included (mean age: 61 ± 8y; mean duration of disease: 8.8 ± 5.4y). Mood symptoms, behavioral disorders and non-motor fluctuations were detected and quantified using the recently validated "Ardouin Scale of Behavior in Parkinson's Disease". Motor symptoms were assessed using UPDRS and quality of life with the "39-item Parkinson's Disease Questionnaire". Results Both motor and non-motor factors significantly affected the quality of life of PD patients. Multivariate regression of the relationship between items of the quality of life questionnaire and the Ardouin Scale showed that alteration of patients' quality of life was strongly correlated with the presence of mood symptoms (such as depression, anxiety ...) and with non-motor fluctuations (especially in the OFF period). A significant correlation was also found between the number of symptoms and their severity, and the quality of life deterioration. Some behavioral disorders (compulsive buying / eating behavior) also negatively affected patient's quality of life to a lesser extent. Alternatively, excess in motivation and hobbyism behaviors had a positive impact on mobility and emotional well-being dimensions respectively of quality of life. Conclusions This study shows the main impact of mood symptoms and non-motor fluctuations on worsening quality of life in PD.
Published: 2016
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47. Préservation de la fertilité et accès à l’assistance médicale à la procréation chez les personnes Trans : recommandations de Trans Santé France

Author: Brouillet, Sophie, Ducrocq, B, Mestres, S, Guillemain, C, Ravel, C, Reignier, A, Développement Embryonnaire, Fertilité et Environnement (DEFE), 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)-Université de Montpellier (UM), CHU Lille, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Centre Clinico-Biologique d’Assistance Médicale à la Procréation - CECOS [Hôpital de la Conception - APHM], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École des Hautes Études en Santé Publique [EHESP] (EHESP), Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI), 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 hospitalier universitaire de Nantes (CHU Nantes), and Chard-Hutchinson, Xavier
Subjects: Loi de bioéthique, Transgenre, Assisted Reproduction Technology, [SDV]Life Sciences [q-bio], Obstetrics and Gynecology, Transidentity, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Préservation de la fertilité, [SDV] Life Sciences [q-bio], [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Reproductive Medicine, Transgender, Assistance médicale à la procréation, Transidentité, Fertility preservation, [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology
Abstract: Many health care professionals are dealing with the issue of transgender people in their medical practice. In the field of reproduction, Trans people can benefit from fertility preservation before the introduction of hormonal treatment or surgery altering their fertility. This article, which is the result of a collaborative work of several reproductive professionals involved in the health of Trans people, provides an overview of the possibilities of fertility preservation and medically assisted reproduction techniques in France for Trans people., Un nombre croissant de personnes en transition sollicitent les centres autorisés à la préservation de la fertilité en vue de conserver leurs gamètes. Il est actuellement recommandé d’informer les personnes Trans sur leur fertilité actuelle et future, et de leur proposer une congélation de gamètes si leur fertilité est à risque d’être altérée par la prise d’un traitement hormonal ou la réalisation d’une chirurgie sur les gonades. Cet article est issu du travail collaboratif de plusieurs professionnels de la Reproduction impliqués dans la prise en charge des personnes Trans. Il propose un état des lieux des possibilités actuelles en préservation de fertilité et de l’utilisation des gamètes congelés/décongelés en France pour les personnes Trans.
Published: 2022
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48. New electrophysiological mapping combined with MRI in parkinsonian’s subthalamic region

Author: Jean-Jacques Lemaire, Laurent Sarry, Philippe Derost, Jean Gabrillargues, Jerome Coste, Lemlih Ouchchane, Simone Hemm, Franck Durif, Service de Neurochirurgie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Equipe de Recherche en Signal et Imagerie Medicale (ERIM-ERI 14), Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie [CHU Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Service de Neurochirurgie A [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], and Coste, Jérôme
Subjects: Male, Deep brain stimulation, Parkinson's disease, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, medicine.medical_treatment, Action Potentials, Substantia nigra, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Premovement neuronal activity, spontaneous activity, Aged, 030304 developmental biology, Neurons, Brain Mapping, subthalamic nucleus, 0303 health sciences, medicine.diagnostic_test, business.industry, General Neuroscience, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Parkinson Disease, Magnetic resonance imaging, Middle Aged, electrophysiology, medicine.disease, Magnetic Resonance Imaging, deep brain stimulation, Electrophysiology, Subthalamic nucleus, medicine.anatomical_structure, nervous system, Zona incerta, Female, business, Neuroscience, 030217 neurology & neurosurgery
Abstract: International audience; The subthalamic nucleus (STN) is the main target for deep brain stimulation in Parkinson's disease. We analysed the relationships between magnetic resonance imaging (MRI) anatomy and spontaneous neuronal activity to confirm the potential of microelectrode recordings to assist in determining the optimal surgical target. Ten bilateral surgeries were performed after 1.5-T (T2-weighted) anatomical MRI identification of the STN, zona incerta (ZI), Forel's field H2 (H2) and substantia nigra (SN). Spontaneous neuronal activity was recorded simultaneously along the distal 10 mm on a central track (optimally covering the STN) and a 2-mm anterior track. We calculated off-line mean firing rate and burst frequency on 248 neurons clustered according to anatomical structure. Subjective visual analysis of signal was also realized on-line, during surgery, to classify patterns of activity. Mean firing rate and burst frequency increased from H2–ZI to SN. The mean firing rate was higher in SN only using paired comparison (SN vs. its neighbours). The burst frequency was lower in H2 than in SN; using comparison with neighbours, it was lower in H2 and ZI. An irregular high activity (type 2C) was more often detected in STN and SN than in H2 and ZI. Anatomical boundaries and unitary recordings appear to be linked, supporting the ability of MRI to provide a detailed anatomy. Electrophysiological mapping combined with MRI is a useful tool for precise targeting in the subthalamic region.
Published: 2009
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49. The tumoral A genotype of the MGMT rs34180180 single-nucleotide polymorphism in aggressive gliomas is associated with shorter patients’ survival

Author: Bruno M. Costa, Jean-Louis Kemeny, Pierre Verrelle, Catherine Vaurs-Barrière, Afonso A. Pinto, Bruno Pereira, Lucie Karayan-Tapon, Mélanie Müller-Barthélémy, Franck Court, Julian Biau, Anne Fogli, Philippe Arnaud, Emmanuel Chautard, Toufic Khalil, Service de Biochimie et Génétique Moléculaire [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Faculté de Médecine - Clermont-Ferrand, Université d'Auvergne - Clermont-Ferrand I (UdA), Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Laboratoire de pathologie, Service de Neurochirurgie [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], Institut National de la Transfusion Sanguine [Paris] (INTS), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service de Neurochirurgie [CHU Clermont-Ferrand], Service de Biochimie Médicale et Biologie Moléculaire [CHU Clermont-Ferrand], Génétique, Reproduction et Développement - Clermont Auvergne ( GReD ), IFR79-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Clermont Auvergne ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Université d'Auvergne - Clermont-Ferrand I ( UdA ), Génétique, reproduction et développement ( GReD ), Université Blaise Pascal - Clermont-Ferrand 2 ( UBP ) -Université d'Auvergne - Clermont-Ferrand I ( UdA ) -IFR79-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Biostat Unit, Centre Hospitalier Universitaire de Clermont-Ferrand, Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), CHU Clermont-Ferrand-Hôpital Gabriel Montpied, Institut National de la Transfusion Sanguine [Paris] ( INTS ), Centre Jean Perrin, CRLCC Jean Perrin, [et.al.], and Universidade do Minho
Subjects: Adult, Male, Cancer Research, Methyltransferase, IDH1, Genotype, Single-nucleotide polymorphism, [SDV.CAN]Life Sciences [q-bio]/Cancer, Kaplan-Meier Estimate, Biology, Bioinformatics, Polymerase Chain Reaction, Polymorphism, Single Nucleotide, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Glioma, medicine, Humans, Promoter Regions, Genetic, [ SDV.GEN.GH ] Life Sciences [q-bio]/Genetics/Human genetics, DNA Modification Methylases, neoplasms, ComputingMilieux_MISCELLANEOUS, Proportional Hazards Models, Retrospective Studies, Temozolomide, Brain Neoplasms, Tumor Suppressor Proteins, Promoter, General Medicine, Methylation, DNA Methylation, Prognosis, medicine.disease, digestive system diseases, 3. Good health, DNA Repair Enzymes, CpG site, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, 030220 oncology & carcinogenesis, Cancer research, Female, Polymorphism, Restriction Fragment Length, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: Malignant gliomas are the most common primary brain tumors. Grade III and IV gliomas harboring wild-type IDH1/2 are the most aggressive. In addition to surgery and radiotherapy, concomitant and adjuvant chemotherapy with temozolomide (TMZ) significantly improves overall survival (OS). The methylation status of the O-6-methylguanine-DNA methyltransferase (MGMT) promoter is predictive of TMZ response and a prognostic marker of cancer outcome. However, the promoter regions the methylation of which correlates best with survival in aggressive glioma and whether the promoter methylation status predictive value could be refined or improved by other MGMT-associated molecular markers are not precisely known. In a cohort of 87 malignant gliomas treated with radiotherapy and TMZ-based chemotherapy, we retrospectively determined the MGMT promoter methylation status, genotyped single nucleotide polymorphisms (SNPs) in the promoter region and quantified MGMT mRNA expression level. Each of these variables was correlated with each other and with the patients' OS. We found that methylation of the CpG sites within MGMT exon 1 best correlated with OS and MGMT expression levels, and confirmed MGMT methylation as a stronger independent prognostic factor compared to MGMT transcription levels. Our main finding is that the presence of only the A allele at the rs34180180 SNP in the tumor was significantly associated with shorter OS, independently of the MGMT methylation status. In conclusion, in the clinic, rs34180180 SNP genotyping could improve the prognostic value of the MGMT promoter methylation assay in patients with aggressive glioma treated with TMZ., ARC -Fondation ARC pour la Recherche sur le Cancer(EML20120904843)
Published: 2016
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50. Proton MR Spectroscopy for Diagnosis and Evaluation of Treatment Efficacy in Parkinson Disease

Author: Leslie Mazuel, Bruno Pereira, Claudine Speziale, Aurélie Cladière, Carine Chassain, Franck Durif, Betty Jean, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), CHU Clermont-Ferrand, Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Département Neurologie, Service de Neurologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], Douhairie, Marie-Laurence, Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-CHU Clermont-Ferrand, CHU Estaing [Clermont-Ferrand], and CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand]
Subjects: Oncology, Male, medicine.medical_specialty, Pathology, Magnetic Resonance Spectroscopy, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.NEU.PC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Disease, 030218 nuclear medicine & medical imaging, Antiparkinson Agents, 03 medical and health sciences, 0302 clinical medicine, Text mining, Internal medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, Prospective Studies, ComputingMilieux_MISCELLANEOUS, Aged, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, business.industry, Total creatine, Putamen, [SCCO.NEUR]Cognitive science/Neuroscience, T-cell receptor, Dopaminergic, [SCCO.NEUR] Cognitive science/Neuroscience, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Reproducibility of Results, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Parkinson Disease, Middle Aged, Proton mr spectroscopy, Treatment efficacy, 3. Good health, Treatment Outcome, Case-Control Studies, Female, Protons, business, 030217 neurology & neurosurgery, [SDV.NEU.SC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences
Abstract: To assess the neurochemical profile in the putamen of patients with parkinsonian syndromes undergoing L-3,4-dihydroxyphenylalanine (L-DOPA) treatment (drug-on) or after withdrawal of L-DOPA medication (drug-off) compared with healthy volunteers to identify dopaminergic therapy-sensitive biomarkers of Parkinson disease.The local institutional review board approved the study, and all participants gave informed consent. A short echo-time (29 msec) single-voxel (1-cm(3)) proton (hydrogen 1 [(1)H]) magnetic resonance (MR) spectroscopic approach was used at 3 T to explore the metabolic profile in the putamen of patients with Parkinson disease. Spectra obtained from 20 healthy volunteers were blindly compared with spectra obtained from 20 patients with parkinsonian syndromes in drug-on and drug-off conditions in a randomized permuted block study to assess the accuracy of diagnostic biomarkers for Parkinson disease and efficacy of L-DOPA therapy. The statistical tests were two sided, with a type-I error set at α of .05. Random-effects models were used to compare healthy subjects and patients with parkinsonian syndromes in drug-on or drug-off conditions.Measured concentrations of putaminal total N-acetylaspartate (tNAA) (8.1 ± 0.2 vs 9.4 ± 0.4; P.01), total creatine (tCr) (7.5 ± 0.2 vs 8.3 ± 0.3; P.01), and myo-inositol (m-Ins) (3.8 ± 0.3 vs 5.6 ± 0.4; P.001) were significantly lower in patients with parkinsonian syndromes in drug-off condition than in healthy volunteers. Moreover, L-DOPA therapy restored tNAA (9.1 ± 0.4 vs 8.1 ± 0.2; P.01) and tCr (8.1 ± 0.3 vs 7.5 ± 0.2; P.01) levels, whereas m-Ins levels remained unchanged. The combined glutamate and glutamine and choline showed no changes in drug-off or drug-on condition compared with those in control subjects.tNAA, tCr, and m-Ins were identified as putative biomarkers of Parkinson disease in the putamen of patients. tNAA and tCr levels are responsive to L-DOPA therapy.
Published: 2016
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