Author: "Service de pharmacologie" - Searchworks@Jio Institute Digital Library Search Results

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4,243 results on '"Service de pharmacologie"'

1. FIbromyalgia anD GenetIcs Subgroups (FIDGIS) (FIDGIS)

Author: Service de pharmacologie et toxicologie cliniques, Hôpitaux Universitaire Genève, Rue Gabrielle Perret-Gentil 4, 1205 Genève, SUISSE and Association des Fibromyalgiques d'Auvergne, 19 Place de la Résistance, 63800 Cournon d'Auvergne, FRANCE
Published: 2022

2. Impact of carpal tunnel syndrome on symptoms and structural severity of hand osteoarthritis: results from the DIGICOD cohort

Author: Hontongnon Julien Djossou, Sophie Tuffet, Alexandra Rousseau, Augustin Latourte, Jean-Denis Laredo, Francis Berenbaum, Jérémie Sellam, Gestionnaire, HAL Sorbonne Université 5, Service de rhumatologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Société IMAGENE, 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), Service de Pharmacologie médicale = service de pharmacologie - Dosage de médicaments [CHU Saint-Antoine], Biologie de l'Os et du Cartilage : Régulations et Ciblages Thérapeutiques (BIOSCAR (UMR_S_1132 / U1132)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de Rhumatologie [CHU Lariboisière], Hôpital Lariboisière-Fernand-Widal [APHP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Cohort Studies, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Rheumatology, Osteoarthritis, Humans, General Medicine, Hand, Carpal Tunnel Syndrome, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2022

3. Determinants of diaphragm inspiratory motion, diaphragm thickening, and its performance for predicting respiratory restrictive pattern in <scp>Duchenne</scp> muscular dystrophy

Author: Nicolas Mansencal, Abdallah Fayssoil, Frédéric Lofaso, H. Prigent, Robert Carlier, Karim Wahbi, Pascal Laforêt, Jean Bergounioux, Tanya Stojkovic, Helge Amthor, Anthony Behin, Guillaume Bassez, Guillaume Nicolas, Djillali Annane, Lee S. Nguyen, Rabah Ben Yaou, Sebastien Damez-Fontaine, David Orlikowski, Justine Zini, Service de réanimation medico-chirurgicale [CHU Raymond-Poincaré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [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), Service de cardiologie et maladies vasculaires [CHU Ambroise Paré], Épidémiologie et recherches translationnelles sur les maladies rénales et cardiovasculaires (EPREC) (U1018 (Équipe 5)), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Handicap neuromusculaire : Physiopathologie, Biothérapie et Pharmacologies appliquées (END-ICAP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), 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), Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), 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), CMC Ambroise Paré [Neuilly-sur-Seine], Service de physiologie et d'explorations fonctionnelles [CHU Raymond-Poincaré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Raymond Poincaré [AP-HP], Service d'Imagerie Médicale [Raymond-Poincaré], Hôpital Raymond Poincaré [AP-HP], Filière Neuromusculaire (FILNEMUS), 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), Analysis-Synthesis Approach for Virtual Human Simulation (MIMETIC), Université de Rennes 2 (UR2)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-RÉALITÉ VIRTUELLE, HUMAINS VIRTUELS, INTERACTIONS ET ROBOTIQUE (IRISA-D5), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Service de biochimie et de génétique moléculaire [CHU Cochin], Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre d’Investigation Clinique 1429 [Garches] (CIC 1429), Hôpital Raymond Poincaré [AP-HP]-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), CIC Paris Est, Centre régional de Pharmacovigilance [CHU Pitié] (CRPV Paris), Service de pharmacologie médicale [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), Dpt Radiologie [CHU Poincaré], Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-MEDIA ET INTERACTIONS (IRISA-D6), Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-CentraleSupélec-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Centre d'investigation clinique Paris Est (CIC Paris-Est), 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre régional de Pharmacovigilance [CHU Pitié] (CRPV Paris Pitié), Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Inria Rennes – Bretagne Atlantique, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique)
Subjects: Duchenne muscular dystrophy, medicine.medical_specialty, Vital capacity, pulmonary, Physiology, Vital Capacity, Pulmonary insufficiency, Inspiratory Capacity, 03 medical and health sciences, Cellular and Molecular Neuroscience, FEV1/FVC ratio, 0302 clinical medicine, Physiology (medical), Internal medicine, medicine, Humans, Respiratory system, Retrospective Studies, 2. Zero hunger, ultrasound, business.industry, Area under the curve, medicine.disease, Respiratory Function Tests, 3. Good health, Diaphragm (structural system), Muscular Dystrophy, Duchenne, 030228 respiratory system, diaphragm, Cardiology, Neurology (clinical), business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract: International audience; Introduction/aims: Respiratory status is a key determinant of prognosis in patients with Duchenne muscular dystrophy (DMD). We aimed to evaluate the determinants of diaphragm ultrasound and its performance in predicting restrictive respiratory patterns in DMD.Methods: This was a retrospective study of DMD patients followed in our center and admitted for an annual checkup from 2015 to 2018. We included DMD patients who underwent diaphragm ultrasound and pulmonary functional tests.Results: This study included 74 patients with DMD. The right diaphragm thickening fraction (TF) was significantly associated with age (P = .001), Walton score (P = .012), inspiratory capacity (IC) (P = .004), upright forced vital capacity (FVC) (P < .0001), supine FVC (P = .038), and maximal inspiratory pressure (MIP) (P = .002). Right diaphragm excursion was significantly associated with age (P < .0001), steroid use (P = .008), history of spinal fusion (P < .0001), body mass index (BMI) (P = .002), Walton score (P < .0001), IC (P < .0001), upright FVC (P < .0001), supine FVC (P < .0001), and MIP (P < .0001). A right diaphragm TF >28% and a right diaphragm excursion>25.4 mm were associated with an FVC >50% with, respectively, an area under the curve (AUC) of 0.95 (P = .001) and 0.93 (P < .001). A left diaphragm TF >26.8% and a left diaphragm excursion >21.5 mm were associated with an FVC >50% with, respectively, an AUC of 0.95 (P = .011) and 0.97 (P < .001).Discussion: Diaphragm excursion and diaphragm TF can predict restrictive pulmonary insufficiency in DMD.
Published: 2021

4. Cardiac adipose tissue volume and IL-6 level at admission are complementary predictors of severity and short-term mortality in COVID-19 diabetic patients

Author: Franck Phan, Samia Boussouar, Olivier Lucidarme, Mohamed Zarai, Joe-Elie Salem, Nadjia Kachenoura, Khaoula Bouazizi, Etienne Charpentier, Yasmine Niati, Hasnae Bekkaoui, Zahir Amoura, Alexis Mathian, Olivier Benveniste, Patrice Cacoub, Yves Allenbach, David Saadoun, Jean-Marc Lacorte, Salma Fourati, Suzanne Laroche, Agnes Hartemann, Olivier Bourron, Fabrizio Andreelli, Alban Redheuil, COVID-19 APHP.SU Group, Service de Diabétologie [CHU Pitié-Salpétrière], 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 de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Radiologie cardiovasculaire et interventionnelle [CHU Pitié-Salpêtrière], Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), HAL-SU, Gestionnaire, Service de diabétologie [CHU Pitié-Salpétrière], Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de radiologie cardiovasculaire et interventionnelle [CHU Pitié-Salpêtrière], Service de pharmacologie médicale [CHU Pitié-Salpêtrière], Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Unité de recherche sur les maladies cardiovasculaires et métaboliques, UMR S 1166, Nutrition et obésités: approches systémiques (nutriomics) (UMR-S 1269 INSERM - Sorbonne Université), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, Endocrinology, Diabetes and Metabolism, Adipose tissue, 030204 cardiovascular system & hematology, Severity of Illness Index, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Mass index, 030212 general & internal medicine, Hospital Mortality, Original Investigation, Outcome, 2. Zero hunger, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Cardiac adipose tissue, Diabetes, Heart, Organ Size, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Prognosis, 3. Good health, Intensive Care Units, Adipose Tissue, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Median body, Female, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, Cardiac computed tomography, 03 medical and health sciences, Internal medicine, Diabetes mellitus, Intensive care, Severity of illness, medicine, Humans, Diseases of the circulatory (Cardiovascular) system, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, Angiology, Aged, Inflammation, business.industry, SARS-CoV-2, Interleukin-6, Myocardium, COVID-19, medicine.disease, Obesity, Diabetes Mellitus, Type 2, RC666-701, business, Tomography, X-Ray Computed
Abstract: BackgroundCOVID-19 diabetic adults are at increased risk of severe forms irrespective of obesity. In patients with type-II diabetes, fat distribution is characterized by visceral and ectopic adipose tissues expansion, resulting in systemic inflammation, which may play a role in driving the COVID-19 cytokine storm. Our aim was to determine if cardiac adipose tissue, combined to interleukin-6 levels, could predict adverse short-term outcomes, death and ICU requirement, in COVID-19 diabetic patients during the 21 days after admission.MethodsEighty one consecutive patients with type-II diabetes admitted for COVID-19 were included. Interleukin-6 measurement and chest computed tomography with total cardiac adipose tissue index (CATi) measurement were performed at admission. The primary outcome was death during the 21 days following admission while intensive care requirement with or without early death (ICU-R) defined the secondary endpoint. Associations of CATi and IL-6 and threshold values to predict the primary and secondary endpoints were determined.ResultsOf the enrolled patients (median age 66 years [IQR: 59–74]), 73% male, median body mass index (BMI) 27 kg/m2[IQR: 24–31]) 20 patients had died from COVID-19, 20 required intensive care and 41 were in conventional care at day 21 after admission. Increased CATi and IL-6 levels were both significantly related to increased early mortality (respectively OR = 6.15, p = 0.002; OR = 18.2,p p = 0.01; OR = 4.86,p = 0.002). These associations remained significant independently of age, sex, BMI as well as troponin-T level and pulmonary lesion extension in CT. We combined CATi and IL-6 levels as a multiplicative interaction score (CATi*IL-6). The cut-point for this score was ≥ 6386 with a sensitivity of 0.90 and a specificity of 0.87 (AUC = 0.88) and an OR of 59.6 for early mortality (p ConclusionsCardiac adipose tissue index and IL-6 determination at admission could help physicians to better identify diabetic patients with a potentially severe and lethal short term course irrespective of obesity. Diabetic patients with high CATi at admission,a fortioriassociated with high IL-6 levels could be a relevant target population to promptly initiate anti-inflammatory therapies.
Published: 2021

5. Sipuleucel‐T associated inflammatory cardiomyopathy: a case report and observations from a large pharmacovigilance database

Author: R. Wayne Kreeger, Sivakumar Ardhanari, Darla K. Liles, C. Bogdan Marcu, D Lynn Morris, Bénédicte Lebrun-Vignes, John Inzerillo, Rahim Jiwani, Kotaro Takeda, Melissa Y.Y. Moey, Joe-Elie Salem, Karyn Prenshaw, East Carolina University [Greenville] (ECU), University of North Carolina System (UNC), Service de Pharmacologie médicale [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), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Epidemiology in Dermatology and Evaluation in Therapeutics (EpiDermE), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Service de pharmacologie médicale [CHU Pitié-Salpêtrière], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Cardiomyopathy, MedDRA, [SDV]Life Sciences [q-bio], Short Communication, Sipuleucel-T, Short Communications, 030204 cardiovascular system & hematology, computer.software_genre, 03 medical and health sciences, Pharmacovigilance, 0302 clinical medicine, medicine, Diseases of the circulatory (Cardiovascular) system, Adverse Drug Reaction Reporting Systems, Humans, 030212 general & internal medicine, Myocardial infarction, cardiovascular diseases, Adverse effect, Prostate cancer, Database, business.industry, Tissue Extracts, Atrial fibrillation, Bayes Theorem, medicine.disease, Cardiotoxicity, 3. Good health, Cardio‐oncology, Cardio-oncology, Myocarditis, Sipuleucel‐T, Heart failure, RC666-701, Immunotherapy, Cardiology and Cardiovascular Medicine, business, computer, Adverse drug reaction
Abstract: International audience; Aims: The major cardiovascular (CV) adverse effects observed with sipuleucel-T from large multi-institutional clinical trials included thromboembolic events, myocardial infarction, and congestive heart failure in up to 0.3% of patients with CV risk factors. The incidence, outcomes, and mechanisms in real-world clinical settings of these CV adverse effects to date have not been fully elucidated. Our study identified a patient with sipuleucel-T-induced inflammatory cardiomyopathy, which led to the identification of CV adverse effects associated with sipuleucel-T from a large pharmacovigilance database and elucidation of its potential mechanisms.Methods and results: Using the MedDRA term 'cardiac disorders' (System Organ Class level), CV adverse events associated with sipuleucel-T versus all other drugs were reviewed from VigiBase, a large pharmacovigilance database. Disproportionality analysis was calculated by the information component (IC), a Bayesian disproportionality indicator. A positive IC025 (IC 95% lower end credibility interval) value (>0) is the traditional threshold used in statistical signal detection at the Uppsala Monitoring Centre. From VigiBase, the total number of CV adverse drug reaction reported with sipuleucel-T was 306 out of a total of 22 980 104 adverse drug reactions in VigiBase on 10/25/2020. MedDRA preferred terms levels were grouped into major CV adverse drug reaction categories where we observed significant reports of myocardial ischaemia, supraventricular tachycardia (particularly atrial fibrillation/atrial flutter), congestive heart failure, and valvular disorders. Myocardial ischemia included acute myocardial infarction (IC025 2.3) with n = 4/26 (15%) of these individual case safety reports considered fatal. Among patients with 'cardiac failure congestive' (IC025 1.5), 11 of these 43 cases (26%) were fatal with 42 (98%) of these cases considered to be solely due to sipuleucel-T.Conclusions: Patients with CV risk factors who are receiving sipuleucel-T may be at higher risk for congestive heart failure, myocardial ischemia, and supraventricular tachycardia. Electrocardiograms during weekly sipuleucel-T infusions and left ventricular function monitoring with echocardiogram should be considered in these patients. Our findings are suggestive of another rare presentation of T-cell-mediated CV toxicity with cancer immunotherapy.
Published: 2021

6. Blood metabolomics uncovers inflammation-associated mitochondrial dysfunction as a potential mechanism underlying ACLF

Author: Moreau, Richard, Clària, Joan, Aguilar, Ferran, Fenaille, François, Lozano, Juanjo, Junot, Christophe, Colsch, Benoit, Caraceni, Paolo, Trebicka, Jonel, Pavesi, Marco, Alessandria, Carlo, Nevens, Frederik, Saliba, Faouzi, Welzel, Tania M., Albillos, Agustin, Gustot, Thierry, Fernández, Javier, Moreno, Christophe, Baldasarre, Maurizio, Zaccherini, Giacomo, Piano, Salvatore, Montagnese, Sara, Vargas, Victor, Genescà, Joan, Solà, Elsa, Bernal, William, Butin, Noémie, Hautbergue, Thaïs, Cholet, Sophie, Castelli, Florence, Jansen, Christian, Steib, Christian, Campion, Daniela, Mookerjee, Raj, Rodríguez-Gandía, Miguel, Soriano, German, Durand, François, Benten, Daniel, Bañares, Rafael, Stauber, Rudolf E., Gronbaek, Henning, Coenraad, Minneke J., Ginès, Pere, Gerbes, Alexander, Jalan, Rajiv, Bernardi, Mauro, Arroyo, Vicente, Angeli, Paolo, BALDASSARRE, MAURIZIO, Service de Pharmacologie et d'Immunoanalyse (SPI), Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Moreau, Richard, Clària, Joan, Aguilar, Ferran, Fenaille, Françoi, Lozano, Juanjo, Junot, Christophe, Colsch, Benoit, Caraceni, Paolo, Trebicka, Jonel, Pavesi, Marco, Alessandria, Carlo, Nevens, Frederik, Saliba, Faouzi, Welzel, Tania M., Albillos, Agustin, Gustot, Thierry, Fernández, Javier, Moreno, Christophe, Baldasarre, Maurizio, Zaccherini, Giacomo, Piano, Salvatore, Montagnese, Sara, Vargas, Victor, Genescà, Joan, Solà, Elsa, Bernal, William, Butin, Noémie, Hautbergue, Thaï, Cholet, Sophie, Castelli, Florence, Jansen, Christian, Steib, Christian, Campion, Daniela, Mookerjee, Raj, Rodríguez-Gandía, Miguel, Soriano, German, Durand, Françoi, Benten, Daniel, Bañares, Rafael, Stauber, Rudolf E., Gronbaek, Henning, Coenraad, Minneke J., Ginès, Pere, Gerbes, Alexander, Jalan, Rajiv, Bernardi, Mauro, Arroyo, Vicente, and Angeli, Paolo
Subjects: 0301 basic medicine, Cirrhosis, Inflammation, Systemic inflammation, 03 medical and health sciences, 0302 clinical medicine, medicine, Metabolome, Decompensation, Biomarkers, CANONIC study, Multiorgan failure, Small-molecules, Kidney, Hepatology, Catabolism, business.industry, Lipidomic, Organ dysfunction, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Biomarker, medicine.disease, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, Multiorgan failure, Small-molecules, Immunology, 030211 gastroenterology & hepatology, medicine.symptom, business
Abstract: Background & Aims: Acute-on-chronic liver failure (ACLF), which develops in patients with cirrhosis, is characterized by intense systemic inflammation and organ failure(s). Because systemic inflammation is energetically expensive, its metabolic costs may result in organ dysfunction/failure. Therefore, we aimed to analyze the blood metabolome in patients with cirrhosis, with and without ACLF. Methods: We performed untargeted metabolomics using liquid chromatography coupled to high-resolution mass spectrometry in serum from 650 patients with AD (acute decompensation of cirrhosis, without ACLF), 181 with ACLF, 43 with compensated cirrhosis, and 29 healthy individuals. Results: Of the 137 annotated metabolites identified, 100 were increased in patients with ACLF of any grade, relative to those with AD, and 38 comprised a distinctive blood metabolite fingerprint for ACLF. Among patients with ACLF, the intensity of the fingerprint increased across ACLF grades, and was similar in patients with kidney failure and in those without, indicating that the fingerprint reflected not only decreased kidney excretion but also altered cell metabolism. The higher the ACLF-associated fingerprint intensity, the higher the plasma levels of inflammatory markers, tumor necrosis factor alpha, soluble CD206, and soluble CD163. ACLF was characterizedbyintense proteolysis andlipolysis; aminoacid catabolism; extra-mitochondrial glucose metabolism through glycolysis, pentose phosphate, and D-glucuronate pathways; depressed mitochondrial ATP-producing fatty acid beta-oxidation; and extramitochondrial amino acid metabolism giving rise to metabotoxins. Conclusions: In ACLF, intense systemic inflammation is associated with blood metabolite accumulation and profound alterations in major metabolic pathways, in particular inhibition of mitochondrial energy production, which may contribute to the development of organ failures. Lay summary: Acute-on-chronic liver failure (ACLF), which develops in patients with cirrhosis, is characterized by intense systemic inflammation and organ failure(s). Because systemic inflammation is energetically expensive, its metabolic costs may result in organ dysfunction/failure. We identified a 38-metabolite blood fingerprint specific for ACLF that revealed mitochondrial dysfunction in peripheral organs. This may contribute to organ failures. (C) 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Published: 2020

7. Myocardial fibrosis assessed by magnetic resonance imaging in asymptomatic heterozygous familial hypercholesterolemia: the cholcoeur study

Author: Gallo, Antonio, Giral, Philippe, Rosenbaum, David, Mattina, Alessandro, Kilinc, Ali, Giron, Alain, Bouazizi, Khaoula, Gueda Moussa, Moussa, Salem, Joe-Elie, Carrié, Alain, Carreau, Valérie, Béliard, Sophie, Bittar, Randa, Cluzel, Philippe, Bruckert, Eric, Redheuil, Alban, Kachenoura, Nadjia, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d’Endocrinologie, Métabolisme et Prévention des Risques Cardio-Vasculaires [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), Tel Aviv University [Tel Aviv], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de pharmacologie médicale [CHU Pitié-Salpêtrière], Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Biochimie Métabolique [CHU Pitié-Salpêtrière], Service de Chirurgie cardiaque et thoracique [CHU Pitié-Salpêtrière], 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), 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), Tel Aviv University (TAU), Laboratoire d'Imagerie Biomédicale [Paris] (LIB), Service d'Endocrinologie, Métabolisme et Prévention des Maladies Cardio-vasculaires [CHU Pitié-Salpêtrière], Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], Gestionnaire, HAL Sorbonne Université 5, Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Diabète athérothrombose et thérapies Réunion Océan Indien (DéTROI), Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU), Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (ISMETT), University of Pittsburgh Medical Center [Pittsburgh, PA, États-Unis] (UPMC), Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), and Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)
Subjects: Adult, Male, cardiovascular risk, Medicine (General), Research paper, [SDV]Life Sciences [q-bio], Familial hypercholesterolemia, primary prevention, Magnetic Resonance Imaging, Cine, cardiac magnetic resonance, Hyperlipoproteinemia Type II, R5-920, Predictive Value of Tests, Prevalence, Humans, Prospective Studies, cardiovascular diseases, cardiovascular imaging, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Myocardium, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Fibrosis, Case-Control Studies, Medicine, Female, genetic dyslipidaemia
Abstract: International audience; Background: Familial Hypercholesterolemia (FH) is an underdiagnosed condition with an increased cardiovascular risk. It is unknown whether lipid accumulation plays a role in structural myocardial changes. Cardiovascular Magnetic Resonance (CMR) is the reference technique for the morpho-functional evaluation of heart chambers through cine sequences and for myocardial tissue characterization through late gadolinium enhancement (LGE) and T1 mapping images. We aimed to assess the prevalence of myocardial fibrosis in FH patients.Methods: Seventy-two asymptomatic subjects with genetically confirmed FH (mean age 49·24, range 40 to 60 years) were prospectively recruited along with 31 controls without dyslipidaemia matched for age, sex, BMI, and other cardiovascular risk factors. All underwent CMR including cine, LGE, pre- and post-contrast T1 mapping. Extracellular volume (ECV) and enhancement rate of the myocardium (ERM = difference between pre- and post-contrast myocardial T1, normalized by pre-contrast myocardial T1) were calculated.Findings: Five FH patients and none of the controls had intramyocardial LGE (p= 0·188). While no changes in Native T1 and ECV were found, post-contrast T1 was significantly lower (430·6 ± 55ms vs. 476·1 ± 43ms, p
Published: 2021

8. The effect of camelina oil on vascular function in essential hypertensive patients with metabolic syndrome

Author: Bellien, Jeremy, Bozec, Erwan, Bounoure, Frédéric, Khettab, Hakim, Malloizel-Delaunay, Julie, Skiba, Mohamed, Iacob, Michèle, Donnadieu, Nathalie, Coquard, Aude, Morio, Béatrice, Laillet, Brigitte, Rigaudière, Jean-Paul, Chardigny, Jean-Michel, Monteil, Christelle, Vendeville, Cathy, Mercier, Alain, Cailleux, Anne-Françoise, Blanchard, Anne, Amar, Jacques, Fezeu, Léopold, Pannier, Bruno, Bura-Rivière, Alessandra, Boutouyrie, Pierre, Joannidès, Robinson, Service de pharmacologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre d'Investigation Clinique [CHU Rouen] (CIC Rouen), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Endothélium, valvulopathies et insuffisance cardiaque (EnVI), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), 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 de Paris (UP), Différenciation et communication neuronale et neuroendocrine (DC2N), Service de Pharmacologie, AP-HP, HEGP, Service de Médecine Vasculaire [CHU Toulouse], Centre Hospitalier Régional Universitaire de Toulouse (CHRU Toulouse), Pharmacie [CHU Rouen], Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Clermont Auvergne, CRNH Auvergne, UFR Santé, Médecine et Biologie Humaine (UFR SMBH), Université Sorbonne Paris Nord, Centre d'Investigation Clinique (CIC)-INSERM 1404, CIC - HEGP (CIC 1418), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-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), Department of Arterial Hypertension, Toulouse University III, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Department of Nephrology, Centre Hospitalier F.H. Manhès, Université de Paris, Service de Pharmacologie, INSERM U970, équipe 7, Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, 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), Service de pharmacie [CHU HEGP], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre de Recherche en Nutrition Humaine Auvergne [CHU Clermont-Ferrand] (CRNH A), Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-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), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service d'hypertension artérielle et thérapeutique [CHU Toulouse] (HTA et thérapeutique), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Néphrologie [CH Manhès, Fleury-Mérogis], Centre Hospitalier Manhès [Fleury-Mérogis], Biologie et pharmacologie de l'insuffisence cardiaque = Cellular, Molecular and Physiological Mechanisms of Heart Failure, and 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)-Hôpital Européen Georges Pompidou [APHP] (HEGP)
Subjects: Pathologic, Cyclodextrins, Eicosapentaenoic acid, Camelina oil, Insulin resistance, Vascular function, Metabolic syndrome, Dilatation, Essential hypertension, C-reactive protein, Cardiovascular system, Plasma, Fluid flow, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Metabolic syndrome x, Hypertension, Lipds, Thiobarbituric acid reactive substances, Endothelium, Alpha-linolenic acid
Abstract: International audience; Background The effects of a dietary supplementation with the vegetable omega-3 α-linolenic acid (ALA) on cardiovascular homeostasis are unclear. In this context, it would be interesting to assess the effects of camelina oil. Objective This study aimed to assess the cardiovascular and metabolic effects of camelina oil in hypertensive patients with metabolic syndrome. Methods In a double-blind placebo-controlled randomized study, treated essential hypertensive patients with metabolic syndrome received during 6 months either cyclodextrin-complexed camelina oil containing ≈ 1.5 g ALA/day (n = 40), or an isocaloric placebo (n = 41), consisting in the same quantity of cyclodextrins and wheat starch. Anthropometric data, plasma lipids, glycemia, insulinemia, creatininemia, thiobarbituric acid reactive substances, high-sensitivity C-reactive protein, and n-3, n-6 and n-9 fatty acids in erythrocyte membranes were measured. Peripheral and central blood pressures, arterial stiffness, carotid intima-media thickness and brachial artery endothelium-dependent flow-mediated dilatation and endothelium-independent dilatation were assessed. Results Compared to placebo, camelina oil increased ALA (mean ± SD: 0 ± 0.04 vs. 0.08 ± 0.06%, P
Published: 2021

9. Simple Approach to Enhance Green Tea Epigallocatechin Gallate Stability in Aqueous Solutions and Bioavailability: Experimental and Theoretical Characterizations

Author: Philippe-Henri Secretan, Olivier Thirion, Hassane Sadou Yayé, Thibaud Damy, Alain Astier, Muriel Paul, Bernard Do, Groupe matériaux et santé, Université Paris-Saclay, CHU Henri Mondor, Service de Pharmacologie médicale [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), Epidemiology in Dermatology and Evaluation in Therapeutics (EpiDermE), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de pharmacologie médicale [CHU Pitié-Salpêtrière], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: epigallocatechin gallate, Pharmaceutical Science, formulation, 010402 general chemistry, 01 natural sciences, complex mixtures, Article, Pharmacy and materia medica, Drug Discovery, heterocyclic compounds, density functional theory, mass spectrometry, 010405 organic chemistry, food and beverages, oral solution, stability, 3. Good health, 0104 chemical sciences, RS1-441, Molecular Medicine, Medicine, complex, sense organs, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Because of its antioxidant, antimutagenic, and anti-infectious properties, epigallocatechin gallate (EGCG) is the most interesting compound among the green tea catechins polyphenols. However, its health effects are inconclusive due to its very low bioavailability, largely due to a particular instability that does not allow EGCG to reach the potency required for clinical developments. Over the last decade, many efforts have been made to improve the stability and bioavailability of EGCG using complex delivery systems such as nanotechnology, but these efforts have not been successful and easy to translate to industrial use. To meet the needs of a large-scale clinical trial requiring EGCG in a concentrated solution to anticipate swallowing impairments, we developed an EGCG-based aqueous solution in the simplest way while trying to circumvent EGCG instability. The solution was thoroughly characterized to sort out the unexpected stability outcome by combining experimental (HPLC-UV-mass spectrometry and infrared spectroscopy) and computational (density functional theory) studies. Against all odds, the EGCG–sucrose complex under certain conditions may have prevented EGCG from degradation in aqueous media. Indeed, in agreement with the ICH guidelines, the formulated solution was shown to be stable up to at least 24 months under 2–8 °C and at ambient temperature. Furthermore, considerable improvement in bioavailability in rats, against EGCG powder formulated in hard-gel capsules, was shown after gavage. Thus, the proposed formulation may provide an easily implementable platform to administer EGCG in the context of clinical development.
Published: 2021

10. Clostridioides difficile Infection Rates after Ceftolozane–Tazobactam and Ceftazidime–Avibactam Treatment Compared to Carbapenem Treatment: A Retrospective Single-Center Study

Author: Nagisa Godefroy, Jérôme Robert, Laurence Drieux-Rouzet, Helga Junot, Charles-Edouard Luyt, Alexandre Bleibtreu, Cyril Méloni, Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de pharmacologie médicale [CHU Pitié-Salpêtrière], Service de Bactériologie et d'Hygiène Hospitalière [CHU Pitié-Salpêtrière], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], 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), 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), Centre d'Immunologie et des Maladies Infectieuses (CIMI), and Gestionnaire, HAL Sorbonne Université 5
Subjects: medicine.medical_specialty, Carbapenem, genetic structures, medicine.drug_class, Antibiotics, Single Center, Clostridioides difficile, antibiotics, Ceftazidime–avibactam, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, 030212 general & internal medicine, 0303 health sciences, gut microbiota, 030306 microbiology, business.industry, Significant difference, CEFTOLOZANE/TAZOBACTAM, Ceftazidime/avibactam, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Exact test, Ceftolozane–tazobactam, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, business, Clostridioides, medicine.drug
Abstract: Introduction: Ceftolozane–tazobactam (CT) and ceftazidime–avibactam (CZA) are new beta-lactam/beta-lactamase inhibitors (BL/IBL) and antibiotics. There are few data regarding their impact on Clostridioides difficile infections (CDI). The objective of our study was, therefore, to determine and compare the number of CDI occurring after treatment with CT or CZA and carbapenem (CBP). Methods: All patients who received at least one dose of CT or CZA in our hospital between 1 January 2018 and 31 December 2019 were included. We compared, during the same period, the number of CDI after CT or CZA treatment and CBPs by using a chi-square test of Fischer’s exact test when required. p value &lt, 0.05 was considered as significant. Results: Among the 53 patients receiving CZA and 42 patients receiving CT, two and one, respectively, developed a CDI within 90 days. Of the three (3%) patients who developed a CDI, one died 15 days after his second CDI (36 days after initiation of CZA). Of the 2291 patients receiving CBP, 37 (1.6%) developed a CDI within 90 days. There was no significant difference between the number of CDI occurring after CBP and CT or CZA treatment. CT or CZA use is not associated with an increased rate of CDI compared to CBP.
Published: 2021

11. Deep learning analysis of ECG for risk prediction of drug-induced arrhythmias and diagnosis of long QT syndrome

Author: Prifti, Edi, Fall, Ahmad, Davogustto, Giovanni, Pulini, Alfredo, Denjoy, Isabelle, Funck-Brentano, Christian, Khan, Yasmin, Durand-Salmon, Alexandre, Badilini, Fabio, Wells, Quinn, Leenhardt, Antoine, Zucker, Jean-Daniel, Roden, Dan, Extramiana, Fabrice, Salem, Joe-Elie, Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité de modélisation mathématique et informatique des systèmes complexes [Bondy] (UMMISCO), Université de Yaoundé I-Institut de la francophonie pour l'informatique-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cadi Ayyad [Marrakech] (UCA)-Sorbonne Université (SU)-Institut de Recherche pour le Développement (IRD [France-Nord]), Vanderbilt University [Nashville], UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Université Paris Cité (UPCité), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Groupe de REcherche en Cardio Oncologie (GRC 27 - GRECO), Sorbonne Université (SU), Cardiabase-Banook group [Nancy], AMPS-LLC [New York], Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Service de Pharmacologie médicale [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), Groupe de REcherche en Cardio Oncologie [CHU Saint-Antoine] (GRC 27 GRECO), CHU Saint-Antoine [AP-HP], HAL-SU, Gestionnaire, Nutrition et obésités: approches systémiques (nutriomics) (UMR-S 1269 INSERM - Sorbonne Université), Institut de Recherche pour le Développement (IRD [France-Nord])-Institut de la francophonie pour l'informatique-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cadi Ayyad [Marrakech] (UCA)-Université de Yaoundé I-Sorbonne Université (SU), Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), Service de pharmacologie médicale [CHU Pitié-Salpêtrière], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: risk prediction, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, machine learning, Torsades de Pointes, long QT, cardiovascular diseases, interpretability, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Aims: Congenital (cLQTS) or drug-induced (diLQTS) long-QT syndromes can cause Torsadede-Pointes (TdP), a life-threatening ventricular arrhythmia. The current strategy for identification of drugs at high-risk of TdP relies on measuring the QT-interval corrected for heart rate (QTc) on ECG. However, QTc has a low positive predictive value. Methods: We used convolutional-neural-network (CNN) models to quantify ECG alterations induced by sotalol, an IKr-blocker associated with TdP, aiming to provide new tools (CNN-models) to enhance prediction of diTdP and diagnosis of cLQTS. Tested CNN-models used single or multiple 10sec recordings/patient using 8 leads or single leads in various cohorts: 1029 healthy subjects before and after sotalol intake (n=14135 ECGs); 487 cLQTS patients (n=1083 ECGs: 560 type 1, 456 type 2, 67 type 3); 48 patients with diTdP (n=1105 ECGs, with 147 obtained within 48hours of a diTdP episode). Results: CNN-models outperformed models using QTc to identify exposure to sotalol (ROC-AUC=0.98 vs. 0.72,p≤0.001). CNN-models had higher ROC-AUC using multiple vs. single 10s-ECG (p≤0.001). Performances were comparable for 8-lead vs. single lead models. CNN-models predicting sotalol exposure also accurately detected presence and type of cLQTS vs. healthy controls, particularly for cLQT2 (AUC-ROC=0.9), and were greatest shortly after a diTdP event and declining over time(p≤0.001), after controlling for QTc and intake of culprit drugs. ECG segment analysis identified the J-Tpeak interval as the best discriminator of sotalol intake. Conclusion: CNN-models applied to ECGs outperform QTc measurements to identify exposure to drugs altering the QT-interval, congenital LQTS, and are greatest shortly after a diTdP episode.
Published: 2021

12. Non-invasive and invasive brain stimulation in alcohol use disorders: A critical review of selected human evidence and methodological considerations to guide future research

Author: K. Bihan, L. Silveira-Reis-Brito, Antoni Valero-Cabré, Redwan Maatoug, Philibert Duriez, Bruno Millet, A. Benyamina, P. Podevin, Service de psychiatrie adulte [CHU Pitié-Salpêtière], 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), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de pharmacologie médicale [CHU Pitié-Salpêtrière], Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Clinique des maladies mentales et de l'encéphale (CMME - Service de psychiatrie), Hôpital Sainte-Anne-Université de Paris (UP), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Paul Brousse, Boston University [Boston] (BU), Open University of Catalonia [Barcelona], Universitat Oberta de Catalunya (UOC), Service de Psychiatrie Adulte [CHU Pitié-Salpêtière], 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), Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Sainte-Anne-Université Paris Cité (UPCité), and Gestionnaire, Hal Sorbonne Université
Subjects: medicine.medical_treatment, [SDV]Life Sciences [q-bio], RC435-571, Craving, Alcohol use disorder, Transcranial Direct Current Stimulation, Brain stimulation techniques, 0302 clinical medicine, Deep brain stimulation, 030212 general & internal medicine, Psychiatry, Transcranial direct-current stimulation, Neuromodulation, Rehabilitation, Brain, Transcranial Magnetic Stimulation, Neuromodulation (medicine), psychiatry, 3. Good health, deep brain stimulation, [SDV] Life Sciences [q-bio], Psychiatry and Mental health, Clinical Psychology, Alcoholism, substance use disorders, neuromodulation, Addictology, medicine.symptom, medicine.medical_specialty, Repetitive transcranial magnetic stimulation, alcohol use disorder, brain stimulation techniques, rehabilitation, 03 medical and health sciences, Physical medicine and rehabilitation, mental disorders, medicine, Humans, Neurostimulation, Substance use disorders, business.industry, transcranial direct-current stimulation, repetitive transcranial magnetic stimulation, medicine.disease, addictology, Transcranial magnetic stimulation, Brain stimulation, Quality of Life, business, 030217 neurology & neurosurgery
Abstract: International audience; Introduction: Alcohol use disorder (AUD) ranks among the leading causes of decrements in disability-adjusted life-years. Long-term exposure to alcohol leads to an imbalance of activity between frontal cortical systems and the striatum, thereby enhancing impulsive behaviours and weakening inhibitory control. Alternative therapeutic approaches such as non-invasive and invasive brain stimulation have gained some momentum in the field of addictology by capitalizing on their ability to target specific anatomical structures and correct abnormalities in dysfunctional brain circuits.Materials and methods: The current review, covers original peer-reviewed published research on the use of brain stimulation methods for the rehabilitation of AUD. A broad and systematic search was carried out on four electronic databases: NCBI PubMed, Web of Science, Handbooks and the Cochrane Library. Any original article in English or French language, without restrictions of patient age or gender, article type and publication outlet, were included in the final pool of selected studies.Results: The outcomes of this systematic review suggest that the dorsolateral prefrontral cortex (DLPFC) is a promising target for treating AUD with high frequency repetitive transcranial magnetic stimulation. Such effect would reduce feelings of craving by enhancing cognitive control and modulating striatal function. Existing literature also supports the notion that changes of DLPFC activity driven by transcranial direct current stimulation, could decrease alcohol craving and consumption. However, to date, no major differences have been found between the efficacy of these two non-invasive brain-stimulation approaches, which require further confirmation. In contrast, beneficial stronger evidence supports an impact of deep brain stimulation reducing craving and improving quality of life in AUD, effects that would be mediated by an impact on the nucleus accumbens, a central structure of the brain's reward circuitry. Overall, neurostimulation shows promise contributing to the treatment of AUD. Nonetheless, progress has been limited by a number of factors such as the low number of controlled randomized trials, small sample sizes, variety of stimulation parameters precluding comparability and incomplete or questionable sham-conditions. Additionally, a lack of data concerning clinical impact on the severity of AUD or craving and the short follow up periods precluding and accurate estimation of effect duration after discontinuing the treatment, has also limited the clinical relevance of final outcomes.Conclusion: Brain stimulation remains a promising approach to contribute to AUD therapy, co-adjuvant of more conventional procedures. However, a stronger therapeutic rational based on solid physio-pathological evidence and accurate estimates of efficacy, are still required to achieve further therapeutic success and expand clinical use.
Published: 2021

13. Efficacy and safety of mexiletine in non-dystrophic myotonias: A randomised, double-blind, placebo-controlled, cross-over study

Author: Vicart, Savine, Franques, Jérôme, Bouhour, Françoise, Magot, Armelle, Péréon, Yann, Sacconi, Sabrina, Nadaj-Pakleza, Aleksandra, Behin, Anthony, Zahr, Noël, Hézode, Marianne, Fournier, Emmanuel, Payan, Christine, Lacomblez, Lucette, Fontaine, Bertrand, 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), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Service d'Electroneuromyographie et Service de Neurologie C [Hôpital Pierre Wertheimer - HCL], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Pasteur [Nice] (CHU), CHU Strasbourg, Service de Pharmacologie médicale [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), Service de Neurophysiologie [CHU Pitié-Salpêtrière], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Gestionnaire, HAL Sorbonne Université 5, Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Service de pharmacologie médicale [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Centre de Recherche en Myologie
Subjects: Muscle channelopathy, Clinical trials, Nondystrophic myotonias, Paramyotonia congenita, Mexiletine, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Myotonia congenita
Abstract: International audience; The MYOMEX study was a multicentre, randomised, double-blind, placebo-controlled, cross-over study aimed to compare the effects of mexiletine vs. placebo in patients with myotonia congenita (MC) and paramyotonia congenita (PC). The primary endpoint was the selfreported score of stiffness severity on a 100 mm visual analogic scale (VAS). Mexiletine treatment started at 200 mg/day and was up-titrated by 200 mg increment each three days to reach a maximum dose of 600 mg/day for total treatment duration of 18 days for each cross-over period. The modified intent-to-treat population included 25 patients (13 with MC and 12 with PC; mean age, 43.0 years; male, 68.0%). The median VAS score for mexiletine was 71.0 at baseline and decreased to 16.0 at the end of the treatment while the score did not change for placebo (81.0 at baseline vs. 78.0 at end of treatment). A mixed effects linear model analysis on ranked absolute changes showed a significant effect of treatment (p < 0.001). The overall score of the Individualized Neuromuscular Quality of Life questionnaire (INQoL) was significantly improved (p < 0.001). No clinically significant adverse events were reported. In conclusion, mexiletine improved stiffness and quality of life in patients with nondystrophic myotonia and was well tolerated.
Published: 2021

14. Dramatic response of STRN-NTRK-fused malignant glioneuronal tumor to larotrectinib in adult

Author: Julie Boyer, Franck Bielle, Cristina Birzu, Carine Karachi, Ahmed Idbaih, Clara Goulas, Julien Savatovsky, HAL-SU, Gestionnaire, 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), Service de neurologie 2 [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de Neuropathologie [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), Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], Fondation Ophtalmologique Adolphe de Rothschild [Paris], Service de Neurochirurgie [CHU Pitié-Salpêtrière], Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Service de pharmacologie médicale [CHU Pitié-Salpêtrière]
Subjects: Adult, NTRK fusion, Cancer Research, Oncogene Proteins, Fusion, molecular targeted therapy, Nerve Tissue Proteins, 01 natural sciences, 03 medical and health sciences, 0302 clinical medicine, Glioneuronal tumor, Neoplasms, Humans, Letters to the Editor, Protein Kinase Inhibitors, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Chemistry, 010401 analytical chemistry, Membrane Proteins, 3. Good health, 0104 chemical sciences, Pyrimidines, Oncology, 030220 oncology & carcinogenesis, Cancer research, Pyrazoles, Calmodulin-Binding Proteins, glioneuronal tumor, Neurology (clinical), [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience
Published: 2021

15. Neutrophil–Platelet and Monocyte–Platelet Aggregates in COVID-19 Patients

Author: David Saadoun, Matheus Vieira, Michelle Rosenzwajg, Arsène Mekinian, David Klatzmann, Lucie Biard, Yacine Boulaftali, Aude Carillion, Patrice Cacoub, Olivier Paccoud, Alexandre Le Joncour, Joe-Elie Salem, Georgina Maalouf, Anne-Geneviève Marcelin, Helene Bugaut, Jean-Christophe Corvol, Mathieu Vautier, Gestionnaire, HAL Sorbonne Université 5, Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), 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), Equipe 2 : ECSTRA - Epidémiologie Clinique, STatistique, pour la Recherche en Santé (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de médecine interne [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), Service de rhumatologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre d'investigation clinique Biothérapie [CHU Pitié-Salpêtrière] (CIC-BTi), Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), 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), Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], 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), 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), Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d’Investigation Clinique intégré en Biothérapies et immunologie [AP-HP pitié-salpêtrière, Paris] (CIC-BTi), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de pharmacologie médicale [CHU Pitié-Salpêtrière], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], and 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)
Subjects: Platelets, 2019-20 coronavirus outbreak, [SDV.IMM] Life Sciences [q-bio]/Immunology, Coronavirus disease 2019 (COVID-19), Figure 1, Neutrophils, References 25, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Monocytes, 03 medical and health sciences, 0302 clinical medicine, interleukin 6 receptor WORD COUNT :1197, Medicine, Platelet, thrombosis, 030304 developmental biology, 0303 health sciences, SARS-CoV-2, business.industry, Monocyte, COVID-19 SARS-CoV-2 Platelets Neutrophils Monocytes Leukocytes-Platelets aggregates thrombosis interleukin 6 receptor WORD COUNT :1197 References 25, COVID-19, Hematology, Leukocytes-Platelets aggregates, Table 1, 3. Good health, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, business
Abstract: International audience; Coronavirus disease 2019 (COVID-19), a viral respiratory illness caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly spread around the world. Besides severe pneumonia with acute respiratory distress syndrome (ARDS), it has been more recently highlighted that SARS-CoV-2 could predispose to thrombotic disease, both in venous and arterial circulations.[1] Lung autopsy from severe COVID-19 patients revealed high recruitment of innate immune cells including neutrophils and macrophages contributing to the cytokine storm as well as microthrombi.[2] Given the central role of platelets in inflammation and thrombosis, and more specifically leucocyte–platelet aggregates that have been implicated in arterial and venous thrombosis, we aimed to explore neutrophil–platelet aggregate (NPA) and monocyte–platelet aggregate (MPA) in patients hospitalized in a medical ward for COVID-19 infection.
Published: 2020

16. Cucurbit[5]uril derivatives as oxygen carriers

Author: Gaspard Huber, Patrick Berthault, Anvi Laetitia Nguyen, Alain Pruvost, Elodie Barruet, Julie Rivollier, Marie-Pierre Heck, Benoît Prieur, Laboratoire Structure et Dynamique par Résonance Magnétique (LCF) (LSDRM), Nanosciences et Innovation pour les Matériaux, la Biomédecine et l'Energie (ex SIS2M) (NIMBE UMR 3685), Institut Rayonnement Matière de Saclay (IRAMIS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Rayonnement Matière de Saclay (IRAMIS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire Interdisciplinaire sur l'Organisation Nanométrique et Supramoléculaire (LIONS), Service de Chimie Bio-Organique et de Marquage (SCBM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Institut Rayonnement Matière de Saclay (IRAMIS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Service de Pharmacologie et d'Immunoanalyse (SPI), and Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay
Subjects: [CHIM.ORGA]Chemical Sciences/Organic chemistry, 010405 organic chemistry, Supramolecular chemistry, chemistry.chemical_element, [CHIM.MATE]Chemical Sciences/Material chemistry, General Chemistry, 010402 general chemistry, 01 natural sciences, Oxygen, supramolecular chemistry, cucurbituril, 0104 chemical sciences, 3. Good health, dissolved gas binding, chemistry, Cucurbituril, oxygen carrier, Polymer chemistry
Abstract: International audience; Cucurbit[n]urils are rigid cage-molecules of pumpkin-like shape, made of n-glycoluril units, able to bind mainly neutral molecules and cations. In this work, we investigate the binding of three cucurbit[5]uril derivatives with dioxygen O$_2$ and show that one of them, namely per-hydroxylated cucurbit[5]uril, (OH)$_{10}$CB[5], is able to significantly bind dioxygen gas at physiological temperature, even in the presence of sodium chloride at the concentration of injectable solution in blood. As cucurbit[n]urils studied up to now reveal low toxicity, per-hydroxylated cucurbit[5]uril appears as a promising precursor to design a host able to transport O$_2$ in a haemoglobin substitute solution.
Published: 2019

17. Quantification of low abundance Yersinia pestis markers in dried blood spots by immuno-capture and quantitative high-resolution targeted mass spectrometry

Author: Elisabeth Carniel, Stéphanie Simon, François Fenaille, Christophe Junot, François Becher, Aline Rifflet, Jérôme Chenau, Sofia Filali, Service de Pharmacologie et d'Immunoanalyse (SPI), Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Yersinia, Institut Pasteur [Paris], French Joint Ministerial Program of R&D against CBRNE risk, Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Institut Pasteur [Paris] (IP)
Subjects: Pore Forming Cytotoxic Proteins, Yersinia pestis, targeted proteomic, High resolution, Biology, 01 natural sciences, Bubonic plague, Microbiology, Mice, 03 medical and health sciences, Limit of Detection, medicine, Animals, Humans, Dried blood, Chromatography, High Pressure Liquid, Spectroscopy, mass spectrometry, 030304 developmental biology, Bioterrorism Agents, validation, Antigens, Bacterial, Plague, 0303 health sciences, Spots, 010401 analytical chemistry, Biomarker, General Medicine, medicine.disease, biology.organism_classification, dried blood spot, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Atomic and Molecular Physics, and Optics, 3. Good health, 0104 chemical sciences, Dried blood spot, pestis, Targeted mass spectrometry, Female, Dried Blood Spot Testing, immunocapture, Biomarkers
Abstract: Plague, caused by the bacterium Yersinia pestis, is still present in several countries worldwide. Besides, Y. pestis has been designated as Tier 1 agent, the highest rank of bioterrorism agents. In this context, reliable diagnostic methods are of great importance. Here, we have developed an original workflow based upon dried blood spot for simplified sampling of clinical specimens, and specific immuno-mass spectrometry monitoring of Y. pestis biomarkers. Targeted proteins were selectively enriched from dried blood spot extracts by multiplex immunocapture using antibody-coated magnetic beads. After accelerated on-beads digestion, proteotypic peptides were monitored by multiplex LC-MS/MS through the parallel reaction monitoring mode. The DBS-IC-MS assay was designed to quantify both F1 and LcrV antigens, although 10-fold lower sensitivity was observed with LcrV. The assay was successfully validated for F1 with a lower limit of quantification at 5 ng·mL−1 in spiked blood, corresponding to only 0.1 ng on spots. In vivo quantification of F1 in blood and organ samples was demonstrated in the mouse model of pneumonic plague. The new assay could help to simplify the laboratory confirmation of positive point of care F1 dipstick.
Published: 2019

18. Immune components of early breastmilk: Association with maternal factors and with reported food allergy in childhood

Author: Mikaïl Berdi, Blandine de Lauzon-Guillain, Karine Adel-Patient, Christophe Junot, Marie-Aline Charles, A. Forhan, François Fenaille, Florence Castelli, Barbara Heude, Service de Pharmacologie et d'Immunoanalyse (SPI), Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Université Paris Saclay (COmUE), Université Sorbonne Paris Cité (COMUE) (USPC), Institut National de la Recherche Agronomique (INRA), Laboratoire d'Etude du Métabolisme des Médicaments (LEMM), Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Médicaments et Technologies pour la Santé (MTS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Fondation pour la Recherche Medicale (FRM), French Ministry of Research: Federative Research Institutes and Cohort Program, INSERM Human Nutrition National Research Program, and Diabetes National Research
Subjects: eden mother-child cohort, [SDV]Life Sciences [q-bio], Immunology, Immunoglobulins, Mothers, Physiology, Cohort Studies, Atopy, 03 medical and health sciences, 0302 clinical medicine, Immune system, Pregnancy, early breastmilk, Food allergy, growth factors, Humans, Immunology and Allergy, Medicine, Prospective Studies, 030212 general & internal medicine, 2. Zero hunger, food allergy, Milk, Human, biology, Gut barrier, business.industry, Infant, Newborn, immune factors, medicine.disease, 3. Good health, 030228 respiratory system, Pediatrics, Perinatology and Child Health, biology.protein, Cytokines, Intercellular Signaling Peptides and Proteins, Female, France, Antibody, business, Birth cohort, Food Hypersensitivity, Medical doctor
Abstract: International audience; Background Breastmilk (BM) may participate in driving gut barrier function and immunity in the neonate. We analyzed immune and growth factor concentrations in early BM and their association with maternal/environmental characteristics and with food allergy (FA) in childhood. Methods One BM sample was collected in maternity from some mothers in the EDEN birth cohort (n = 2002 mother-child dyads). A random selection was performed among available samples (subcohort, n = 272), for which all deliveries were full-term, various maternal/environmental characteristics were recorded, and parents answered yearly the question "Has a medical doctor diagnosed a FA in your child?" (26 parent-reported FA cases). Only samples collected between day 2 and day 6 post-partum were considered for descriptive analysis (n = 263). Samples for all other FA cases available were added to the subcohort (46 additional cases; "casecohort" design). Fifty cytokines, antibodies, and growth factor concentrations were determined using multiplexed kits and analyzed using robust statistical procedures. Results BM components exhibited wide concentration ranges and global day-to-day variation. Different clusters of correlated factors appeared, with components from the main cluster related to maternal diet during pregnancy. Primiparity was positively associated with eleven other components, whereas other factors (eg, maternal atopy and smoking) were related to fewer components. Finally, the casecohort design highlighted a positive association between CXCL10, TNF beta, and IL-2 concentrations and reported FA in childhood. Conclusion Beyond the unique description of early BM composition, we show that immune information transmitted to the neonate is related to various maternal factors and identified components associated with FA diagnosis in childhood.
Published: 2019

19. Role of Cardiac Imaging in the Diagnosis of Immune Checkpoints Inhibitors Related Myocarditis

Author: Stéphane Ederhy, Joe-Elie Salem, Laurent Dercle, Abrar Saqif Hasan, Marion Chauvet-Droit, Pascal Nhan, Samy Ammari, Bruno Pinna, Alban Redheuil, Samia Boussouar, Stephane Champiat, Laurie Soulat-Dufour, Ariel Cohen, Service de Cardiologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], 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), 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), Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Institut Gustave Roussy (IGR), Albert Einstein College of Medicine [New York], Département d'imagerie médicale [Gustave Roussy], Institut de cardiologie [CHU Pitié-Salpêtrière], Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy] (DITEP), Gestionnaire, HAL Sorbonne Université 5, Sorbonne Université (SU), Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), 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), Columbia University Irving Medical Center (CUIMC), LaBoratoire d'Imagerie biOmédicale MultimodAle Paris-Saclay (BIOMAPS), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Imagerie Biomédicale [Paris] (LIB), Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Service de pharmacologie médicale [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Department of Radiology, Gustave Roussy Cancer Campus, Université Paris-Saclay, Villejuif, France, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP]
Subjects: Cancer Research, medicine.medical_specialty, Myocarditis, [SDV]Life Sciences [q-bio], Mini Review, cardiac magnetic resonance imaging, cardiotoxicity, immune checkpoint inhibitor, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Immune system, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Cardiac magnetic resonance imaging, Internal medicine, Case fatality rate, Medicine, cancer, Cardiac imaging, RC254-282, Cardiotoxicity, medicine.diagnostic_test, business.industry, Cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Oncology, 030220 oncology & carcinogenesis, Cardiology, Biomarker (medicine), myocarditis, business
Abstract: International audience; Immune checkpoint inhibitors (ICI) have constituted a paradigm shift in the management of patients with cancer. Their administration is associated with a new spectrum of immune-related toxicities that can affect any organ. In patients treated with ICI, cardiovascular toxicities, particularly myocarditis, occur with a low incidence (
Published: 2021

20. Discovery based high resolution MS/MS analysis for selection of allergen markers in chocolate and broth powder matrices

Author: Karine Adel-Patient, Linda Monaci, E. N. Clare Mills, Anne Catherine Huet, Chiara Nitride, Nathalie Gillard, Marc De Loose, Rosa Pilolli, Elisabetta De Angelis, Olivier Tranquet, Christof Van Poucke, Colette Larré, Hervé Bernard, Institute of Sciences of Food Production (ISPA), Consiglio Nazionale delle Ricerche (CNR), Flanders Research Institute for Agriculture, Fisheries and Food, Belgium, University of Manchester [Manchester], CER Groupe, Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Pharmacologie et d'Immunoanalyse (SPI), Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, European Food Safety Authority (EFSA) GP/EFSA/AFSCO/2017/03, UK Food Standards Agency FS101209 FS101206, Pilolli, Rosa, Van Poucke, Christof, De Angelis, Elisabetta, Nitride, Chiara, de Loose, Marc, Gillard, Nathalie, Huet, Anne-Catherine, Tranquet, Olivier, Larré, Colette, Adel-Patient, Karine, Bernard, Hervé, Mills, E. N. Clare, Monaci, Linda, National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), Research Institute for Agricultural, Fisheries and Food (ILVO), Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: ThRAll, [SDV]Life Sciences [q-bio], High resolution, Peptide, Mass spectrometry, Tandem mass spectrometry, medicine.disease_cause, Discovery analysis, 01 natural sciences, Analytical Chemistry, 0404 agricultural biotechnology, Allergen, Tandem Mass Spectrometry, Protein purification, medicine, Animals, Sample preparation, Chocolate, Peptide markers, chemistry.chemical_classification, Chromatography, Incurred matrix, 010401 analytical chemistry, Selected reaction monitoring, Reproducibility of Results, 04 agricultural and veterinary sciences, General Medicine, Allergens, 040401 food science, 0104 chemical sciences, chemistry, Food allergens, Powders, Food Analysis, Food Science
Abstract: International audience; Peptide marker identification is an important step in development of a mass spectrometry method for multiple allergen detection, since specificity, robustness and sensitivity of the overall analytical method will depend on the reliability of the proteotypic peptides. As part of the development of a multi-analyte reference method, discovery analysis of two incurred food matrices has been undertaken to select the most reliable peptide markers. Six allergenic ingredients (milk, egg, peanut, soybean, hazelnut, and almond) were incurred into either chocolate or broth powder matrix. Different conditions of protein extraction and purification were tested and the tryptic peptide pools were analysed by untargeted high resolution tandem mass spectrometry and the resulting fragmentation spectra were processed via a commercial software for sequence identification. The analysis performed on incurred foods provides both a prototype effective and straightforward sample preparation protocol and delivers reliable peptides to be included in a standardized selected reaction monitoring method.
Published: 2021

21. Simple and accurate quantitative analysis of cefiderocol and ceftobiprole in human plasma using liquid chromatography-isotope dilution tandem mass spectrometry: interest for their therapeutic drug monitoring and pharmacokinetic studies

Author: Noël Zahr, Gaëlle Noe, Dimitri Schlemmer, Nadine Tissot, Helga Junot, Benoit Llopis, Alexandre Bleibtreu, Christian Funck-Brentano, Charles-Edouard Luyt, Pascal Robidou, Olivier Paccoud, Service de Pharmacologie médicale [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), Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], Service de biochimie-hormonologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Cité (UPCité), Service des Maladies infectieuses et tropicales [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Réanimation Médicale [CHU Pitié-Salpétrière], 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), 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), Gestionnaire, HAL Sorbonne Université 5, Service de pharmacologie médicale [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université de Paris (UP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: 0301 basic medicine, Bioanalysis, therapeutic drug monitoring, cephalosporin, 030106 microbiology, Clinical Biochemistry, Ceftobiprole, Tandem mass spectrometry, Mass spectrometry, High-performance liquid chromatography, 03 medical and health sciences, 0302 clinical medicine, Isotopes, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Tandem Mass Spectrometry, cefiderocol, medicine, liquid chromatography, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, Protein precipitation, Humans, [SDV.BV] Life Sciences [q-bio]/Vegetal Biology, 030212 general & internal medicine, Chromatography, High Pressure Liquid, mass spectrometry, Chromatography, medicine.diagnostic_test, Chemistry, Biochemistry (medical), Reproducibility of Results, General Medicine, Triple quadrupole mass spectrometer, Cephalosporins, Therapeutic drug monitoring, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Drug Monitoring, ceftobiprole, Chromatography, Liquid
Abstract: Objectives Cefiderocol and ceftobiprole are new generation cephalosporin antibiotics that exhibit high inter-individual plasma concentration variability that potentially impact their efficacy or toxicity. The aim of this study was to develop and validate a selective, simple, and fast UPLC-MS/MS method for simultaneous quantification of cefiderocol and ceftobiprole in human plasma to enable their therapeutic drug monitoring (TDM) and support PK and PK/PD studies, in particular in critically ill patients. Methods After a simple and fast single-step protein precipitation, cefiderocol and ceftobiprole were separated on a Waters Acquity UPLC BEH C18 column by linear gradient elution; with subsequent detection by Shimadzu MS 8060 triple quadrupole tandem mass spectrometer in a positive ionization mode. Results Analysis time was 5 min per run. The analytical performance of the method in terms of specificity, sensitivity, linearity, precision, accuracy, matrix effect (ME), extraction recovery (ER), limit of quantification, dilution integrity, and stability of analytes under different conditions met all criteria for a bioanalytical method for the quantification of drugs. The calibration curves were linear over the range of 1–200 mg/L for cefiderocol and 0.5–100 mg/L for ceftobiprole with a linear regression coefficient above 0.995 for both. Conclusions A simple, fast, and selective liquid chroma-tography-tandem mass spectrometry method was developed and validated for the simultaneous quantification of cefiderocol and ceftobiprole. This new method was successfully applied to the measurement of plasma concentration of cefiderocol and ceftobiprole in critically ill patients and showed good performance for their therapeutic monitoring and optimizing antibiotic therapy.
Published: 2021

22. Susceptibility Testing Is Key for the Success of Cefiderocol Treatment: A Retrospective Cohort Study

Author: Alexandre Bleibtreu, Laurent Dortet, Remy A. Bonnin, Benjamin Wyplosz, Sophie-Caroline Sacleux, Liliana Mihaila, Hervé Dupont, Helga Junot, Vincent Bunel, Nathalie Grall, Keyvan Razazi, Clara Duran, Pierre Tattevin, Aurélien Dinh, on behalf of the Cefiderocol French Study Group, Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], 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), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Hôpital Paul Brousse, CHU Amiens-Picardie, Service de pharmacologie médicale [CHU Pitié-Salpêtrière], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, CHU Henri Mondor, Service des Maladies Infectieuses et Tropicales [CHU Raymond Poincaré], Hôpital Raymond Poincaré [AP-HP], Hôpital Universitaire Pontchaillou, ARN régulateurs bactériens et médecine (BRM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), This research received no external funding., Gestionnaire, HAL Sorbonne Université 5, Service de Maladies Infectieuses et Tropicales [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 Pharmacologie médicale [CHU Pitié-Salpêtrière], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and CHU Henri Mondor [Créteil]
Subjects: 0301 basic medicine, Microbiology (medical), Carbapenem, medicine.medical_specialty, medicine.drug_class, Klebsiella pneumoniae, respiratory tract infection, 030106 microbiology, Cephalosporin, medicine.disease_cause, Microbiology, carbapenem, 03 medical and health sciences, 0302 clinical medicine, Antibiotic resistance, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, Internal medicine, cefiderocol, Medicine, 030212 general & internal medicine, lcsh:QH301-705.5, biology, Respiratory tract infections, business.industry, Pseudomonas aeruginosa, Brief Report, Retrospective cohort study, bacterial resistance, biology.organism_classification, 3. Good health, Acinetobacter baumannii, lcsh:Biology (General), [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, business, medicine.drug
Abstract: Cefiderocol is a novel siderophore cephalosporin, which has proven in vitro activity against carbapenem-resistant (CR) Gram-negative pathogens and stability towards all carbapenemases. The aim of this study was to describe the first cases of prescriptions and the efficacy of cefiderocol for compassionate use in the 2 months following its access in France. We performed a national retrospective study of all patients who received at least one dose of cefiderocol from 2 November 2018 to 5 November 2019. We collected clinical characteristics and outcome through a standard questionnaire. Bacterial isolates from 12 patients were centralized and analyzed in the French National Reference Center for Antimicrobial Resistance, and sequenced using Illumina technology. Finally, 13 patients from 7 French university hospitals were included in the study. The main type of infection treated by cefiderocol was respiratory tract infections (RTI, n = 10). The targeted bacteria were Pseudomonas aeruginosa (n = 12), including carbapenemase-producing P. aeruginosa (n = 9), Acinetobacter baumannii (n = 2), Klebsiella pneumoniae (n = 1), and Enterobacter hormaechei (n = 1). Overall, of the 12 patients whose samples were analyzed, 5 P. aeruginosa strains were not susceptible to cefiderocol (4 categorized as resistant and 1 as intermediate) according to Clinical and Laboratory Standards Institute (CLSI) breakpoints. If considering susceptible strains, the cure rate was 6/7, while being 0/5 among not-susceptible strains. This study underlines the necessity to test strains in adequate conditions.
Published: 2021

23. Association of smoking reduction and mortality: protocol for a systematic review and meta-analysis of longitudinal observational studies

Author: Henri-Jean Aubin, Ivan Berlin, Sonia Gabriel, Laetitia Ali Oicheih, Hôpital Paul Brousse, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Service de Pharmacologie médicale [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), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Gestionnaire, Hal Sorbonne Université, Service de pharmacologie médicale [CHU Pitié-Salpêtrière], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: medicine.medical_specialty, Epidemiology, medicine.medical_treatment, [SDV]Life Sciences [q-bio], education, MEDLINE, lcsh:Medicine, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Meta-Analysis as Topic, medicine, Humans, 030212 general & internal medicine, Longitudinal Studies, Smoking Reduction, Protocol (science), business.industry, Public health, lcsh:R, substance misuse, public health, Smoking, General Medicine, 3. Good health, [SDV] Life Sciences [q-bio], Meta-analysis, Smoking cessation, Observational study, Smoking Cessation, business, Demography, Systematic Reviews as Topic
Abstract: IntroductionStrong evidence shows that smoking cessation decreases mortality. Much less is known regarding the association between reduction in cigarettes per day (CPD) and mortality. The primary aim of this systematic review is to compare the mortality risk between smokers achieving a sustained reduction of CPD and smokers maintaining their smoking rate. The secondary aims are to compare the mortality risk between smokers achieving complete, sustained smoking cessation and (1) smokers maintaining their smoking rate and (2) smokers who achieved a sustained reduction in smoking rate.Methods and analysisMEDLINE, Web of Sciences and Embase will be searched using a prespecified search strategy, up to 23 November 2020, and will be limited to studies published in English and in French. Longitudinal observational studies using individual data including smokers with at least two distant CPD assessments and a follow-up period of systematic mortality data recording will be included. The main outcome will be the all-cause mortality. The secondary outcome will be specific mortality. The Newcastle-Ottawa Scale will be used to assess the risk of bias of individual studies. Outcomes will be analysed using HRs. All other outcomes’ effect size reported in included studies will be converted in HRs using validated methods.Ethics and disseminationWe intend to publish the results of our review in a peer-reviewed journal and to present the findings at national and international meetings and conferences.PROSPERO registration numberCRD42019138354.
Published: 2021

24. Anti–Interleukin-6 and Janus Kinase Inhibitors for Severe Neurologic Toxicity of Checkpoint Inhibitors

Author: Noël Zahr, Olivier Hermine, Dimitri Psimaras, Nora Kramkimel, Giulia Berzero, Cristina Birzu, Nefeli Valyraki, Alberto Picca, Sorbonne Université - Département de neurologie 2 - Mazarin, Sorbonne Université (SU)-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), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Necker - Enfants Malades [AP-HP], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Service de pharmacologie médicale [CHU Pitié-Salpêtrière], 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), IRCCS San Raffaele Scientific Institute [Milan, Italie], HAL-SU, Gestionnaire, Service d'Onco-neurologie = Département de neurologie 2 [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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], Picca, A., Valyraki, N., Birzu, C., Kramkimel, N., Hermine, O., Zahr, N., Berzero, G., and Psimaras, D.
Subjects: Male, Ruxolitinib, medicine.medical_treatment, Autoimmune diseases, Transverse myelitis, Gastroenterology, Targeted therapy, chemistry.chemical_compound, 0302 clinical medicine, Immune Checkpoint Inhibitors, Melanoma, Cerebrospinal Fluid, biology, Middle Aged, 3. Good health, Nivolumab, Neurology, All Oncology, 030220 oncology & carcinogenesis, Toxicity, Neurotoxicity Syndromes, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, medicine.drug, medicine.medical_specialty, All Immunology, Ipilimumab, [SDV.CAN]Life Sciences [q-bio]/Cancer, Myelitis, Transverse, Antibodies, Monoclonal, Humanized, 03 medical and health sciences, Tocilizumab, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Nitriles, medicine, Humans, Janus Kinase Inhibitors, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Interleukin 6, Clinical/Scientific Notes, business.industry, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Receptors, Interleukin-6, Pyrimidines, chemistry, biology.protein, Pyrazoles, Neurology (clinical), Janus kinase, business, 030217 neurology & neurosurgery
Abstract: Background and ObjectivesTo describe the marked clinical and biological responses of a targeted treatment with anti–interleukin-6 (IL-6)–receptor antibody and Janus kinase (JAK) inhibitors in a patient with a severe, corticoresistant CNS toxicity of immune-checkpoint inhibitor (ICI) therapy.MethodsA 58-year-old man was admitted for subacute paraparesis, urinary retention, and ascending paresthesia. He was under treatment with ipilimumab and nivolumab for metastatic melanoma. Spine MRI disclosed multiple T2-hyperintense, contrast-enhancing longitudinally extensive lesions. A diagnosis of ICI-related acute transverse myelitis was made.ResultsICIs were immediately discontinued, and the patient received high-dose glucocorticoids plus 1 session of plasma exchange, but he did not improve. Based on the marked elevation of CSF IL-6 (505 pg/mL), a second-line targeted therapy with anti-IL-6-receptor tocilizumab (8 mg/kg/mo for 3 infusions) plus JAK inhibitor ruxolitinib (50 mg/d) was administered. Patient neurologic status started to improve shortly after, with corresponding radiologic resolution. At 9 months, the patient was able to walk independently, presenting only slight residual disability while remaining in oncologic partial response.DiscussionOur case suggests that some patients with severe, corticoresistant CNS immune-related toxicities of ICIs may benefit from cytokine blockade. Cytokine measurement in serum and CSF might help in selecting patients for personalized treatment strategies.
Published: 2021

25. Metacarpophalangeal impairment in hand osteoarthritis is not rare and is associated with mechanical factors: Results from the DIGICOD hand osteoarthritis cohort

Author: Kouki, Inès, Tuffet, Sophie, Crema, Michel, Rousseau, Alexandra, Richette, Pascal, Dougados, Maxime, Berenbaum, Francis, Sellam, Jérémie, Courties, Alice, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de rhumatologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Service de pharmacologie - Dosage de médicaments [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut national du sport, de l'expertise et de la performance (INSEP), Service de Rhumatologie [CHU Lariboisière], Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), HAL-SU, Gestionnaire, 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), and Service de Pharmacologie médicale = service de pharmacologie - Dosage de médicaments [CHU Saint-Antoine]
Subjects: [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract: International audience; Objective: To determine the prevalence, distribution and characteristics associated with radiographic metacarpophalangeal (MCP) osteoarthritis (OA).Methods: This is a cross‐sectional study of baseline data from the DIGItal Cohort Osteoarthritis Design, a French monocentric cohort including patients with symptomatic hand OA (HOA). We evaluated the prevalence of radiographic MCP OA defined as ≥2 MCP joints with a Kellgren and Lawrence score ≥2. We compared the prevalence of MCP OA in the dominant and non‐dominant hands. Associations between radiographic MCP OA and patient characteristics were studied using univariable and multivariable logistic regression.Results: Radiographic MCP OA was present in 138 of the 425 patients (32.5%) but was not severe. Patients with MCP OA had a mean age of 69.2±6.9 years, a BMI of 25±4.2 kg/m2, and 86.2% were women. MCP OA was more frequent in the dominant hand and predominated at the 1st and 2nd MCP joints. In the multivariable analysis, MCP OA was associated with older age (OR 1.05, 95%CI [1.01,1.10] for each year), manual occupation (OR 3.74, 95%CI [1.21,11.54]), scaphotrapezial OA (OR 2.18, 95%CI [1.27,3.72]), and a high number of proximal interphalangeal joints with radiographic OA. MCP OA was not associated with metabolic syndrome or HOA symptoms.Conclusion: In this cross‐sectional study using a hospital‐based HOA cohort, radiographic MCP OA was frequent and associated with structural HOA features rather than with symptom severity. Our results suggest that the involvement of MCP joints in HOA is predominantly related to mechanical rather than systemic factors in this population.
Published: 2021

26. Ciguatera fish poisoning in France: experience of the French Poison Control Centre Network from 2012 to 2019

Author: Corinne Schmitt, Luc de Haro, S. Sinno-Tellier, Nathalie Paret, Jérôme Langrand, Nicolas Simon, Nicolas Delcourt, David Boels, Gaël Le Roux, Magali Labadie, Service de Pharmacologie Clinique [AP-HM Hôpital Ste Marguerite], Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Agence française de sécurité sanitaire des aliments, de l'environnement et du travail [Maisons Alfort], Centre antipoison et de toxicovigilance (Lyon) (CAPTV Lyon), Hospices Civils de Lyon (HCL), Service de pharmacologie et de Toxicologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Antipoison et Toxicovigilance du Grand Ouest (Angers) (CAPTV Angers), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre antipoison et de toxicovigilance (Paris) (CAPTV Paris), Université Paris Diderot - Paris 7 (UPD7)-Hôpitaux Universitaires Saint-Louis, Lariboisière, Fernand-Widal, Centre antipoison et de toxicovigilance [CHU Toulouse] (CAPTV Toulouse), Pôle Médecine d'urgences [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Centre antipoison et de toxicovigilance (Bordeaux) (CAPTV Bordeaux), CHU Bordeaux [Bordeaux], Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centres antipoison et de toxicovigilance (CAPTV Angers), Centres antipoison et de toxicovigilance (CAPTV Paris), Centre antipoison et de toxicovigilance (Toulouse) (CAPTV Toulouse), CHU Toulouse [Toulouse]-CHU Purpan, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, and Dupuis, Christine
Subjects: Adult, Poison Control Centers, Ciguatera, Gambierdiscus, Adolescent, Oceans and Seas, [SDV]Life Sciences [q-bio], Poison control, Toxicology, Tourism, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Poison Control Centre, medicine, Humans, marine toxicology, 030212 general & internal medicine, 14. Life underwater, Child, health care economics and organizations, Ciguatera fish poisoning, Aged, Retrospective Studies, biology, Ciguatera Poisoning, Endemic area, 030208 emergency & critical care medicine, General Medicine, Middle Aged, bacterial infections and mycoses, medicine.disease, biology.organism_classification, 3. Good health, [SDV] Life Sciences [q-bio], Fishery, Geography, Child, Preschool, France, cold allodynia
Abstract: International audience; Introduction: Ciguatera fish poisoning (CFP) is a common Poisoning in the tropical countries. France is directly concerned with French tourists in endemic area and with French citizens living in the French overseas territories. Method: Retrospective, descriptive study of CFP cases handled by the French Poison Control Centre Network from 2012 through 2019. Results: Fifty-two events were studied concerning 130 patients. The fish species was identified for 41 events, mainly belonging to five fish families: 14 groupers, 11 snappers, 5 jacks, 4 parrotfishes, 4 barracudas. The origin of the fish was the Atlantic Ocean (23 events), the Indian Ocean (17 events) and the Pacific Ocean (12 events). 91% of the poisonings occurring in the Atlantic Ocean began with gastrointestinal effects while in 44% of events occurring in the Pacific Ocean, the patients had no gastrointestinal effects (onset with neurological symptoms: paraesthesia and dysesthesia). The evolution of the 130 patients has been classic for CFP with persistent symptoms during 1 to 45 weeks. Numerous patients reported exacerbation of neurological signs several months after poisoning following consumption of alcoholic beverages (23 patients) or seafood (19 patients). Discussion: Medical practitioners in Europe must be trained to manage CFP as cases are reported with tourists returning from endemic areas but also with poisoned patients far from tropical areas after consumption of imported fish.
Published: 2021

27. Pharmacokinetics and pharmacodynamics of hydroxychloroquine in hospitalized patients with COVID-19

Author: Noël Zahr, Valérie Pourcher, Julien Mayaux, Joe-Elie Salem, Estelle Gandjbakhch, Yves Allenbach, Guillaume Hékimian, Saïk Urien, Alexandre Bleibtreu, Olivier Benveniste, Olivier Paccoud, Alain Combes, Christian Funck-Brentano, Benoit Llopis, David Saadoun, Patrice Cacoub, Bruno Pinna, Service de pharmacologie médicale [CHU Pitié-Salpêtrière], 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), Département de Pharmacologie Clinique [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), Service de Cardiologie [CHU Pitié-Salpêtrière], Service de Réanimation Médicale [CHU Pitié-Salpétrière], Centre National de Référence du Lupus Systémique, Syndrome des Anticorps Anti-phospholipides et Maladies Auto-immunes Systémiques Rares [CHU Pitié Salpêtrière], Service de Médecine Interne 2, maladies auto-immunes et systémiques [CHU Pitié-Salpêtrière], Institut E3M [CHU Pitié-Salpêtrière], 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 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)-Institut E3M [CHU Pitié-Salpêtrière], HAL-SU, Gestionnaire, Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de recherche en Myologie – U974 SU-INSERM, Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut E3M [CHU Pitié-Salpêtrière], and Garnier, Sophie
Subjects: Adult, Male, medicine.medical_specialty, 030226 pharmacology & pharmacy, High-performance liquid chromatography, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, Intensive care, medicine, Humans, Pharmacology (medical), Retrospective Studies, Volume of distribution, [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, SARS-CoV-2, business.industry, Clinical Pharmacology, Hydroxychloroquine, Middle Aged, Confidence interval, COVID-19 Drug Treatment, 3. Good health, Bioavailability, Hospitalization, [SDV] Life Sciences [q-bio], Pharmacodynamics, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Female, business, Covid-19, medicine.drug
Abstract: Summary Background Hydroxychloroquine (HCQ) dosage required to reach circulating levels that inhibit SARS-Cov-2 are extrapolated from pharmacokinetic data in non-COVID-19 patients. Methods We performed a population-pharmacokinetic analysis from 104 consecutive COVID-19 hospitalized patients (31 in intensive care units, 73 in medical wards, n = 149 samples). Plasma HCQ concentration were measured using high performance liquid chromatography with fluorometric detection. Modelling used Monolix-2019R2. Results HCQ doses ranged from 200 to 800 mg/day administered for 1 to 11 days and median HCQ plasma concentration was 151 ng/mL. Among the tested covariates, only bodyweight influenced elimination oral clearance (CL) and apparent volume of distribution (Vd). CL/F (F for unknown bioavailability) and Vd/F (relative standard-error, %) estimates were 45.9 L/h (21.2) and 6690 L (16.1). The derived elimination half-life (t1/2) was 102 h. These parameters in COVID-19 differed from those reported in patients with lupus, where CL/F, Vd/F and t1/2 are reported to be 68 L/h, 2440 L and 19.5 h, respectively. Within 72 h of HCQ initiation, only 16/104 (15.4%) COVID-19 patients had HCQ plasma levels above the in vitro half maximal effective concentration of HCQ against SARS-CoV-2 (240 ng/mL). HCQ did not influence inflammation status (assessed by C-reactive protein) or SARS-CoV-2 viral clearance (assessed by real-time reverse transcription-PCR nasopharyngeal swabs). Conclusion The interindividual variability of HCQ pharmacokinetic parameters in severe COVID-19 patients was important and differed from that previously reported in non-COVID-19 patients. Loading doses of 1600 mg HCQ followed by 600 mg daily doses are needed to reach concentrations relevant to SARS-CoV-2 inhibition within 72 hours in ≥ 60% (95% confidence interval: 49.5–69.0%) of COVID-19 patients.
Published: 2021

28. Management of Immune Checkpoint Inhibitor-Induced Myocarditis The French Working Group's Plea for a Pragmatic Approach

Author: Thuny, Franck, Alexandre, Joachim, Salem, Joe-Elie, Mirabel, Mariana, Dolladille, Charles, Cohen-Solal, Alain, Cohen, Ariel, Ederhy, Stéphane, Cautela, Jennifer, Assistance Publique - Hôpitaux de Marseille (APHM), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de pharmacologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), 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), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Université Sorbonne Paris Nord, Service de Cardiologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], 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)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Gestionnaire, Hal Sorbonne Université, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2021

29. A genetic mouse model recapitulates immune checkpoint inhibitor-associated myocarditis and supports a mechanism-based therapeutic intervention

Author: Margaret L Axelrod, Bjorn C. Knollmann, Lauren I.R. Ehrlich, Justin M. Balko, Joe-Elie Salem, James P. Allison, Javid Moslehi, Jing Wang, Padmanee Sharma, Nana Ama A.S. Anang, Jayashree Srinivasan, James J. Mancuso, Oluwatomisin T. Atolagbe, Elles M. Screever, Wouter C. Meijers, Elizabeth M. Whitley, Lorenz H. Lehmann, Lauren E. Himmel, Matthew Wleklinski, Pierre-Yves Courand, Elizabeth Wescott, Bénédicte Lebrun-Vignes, Douglas B. Johnson, Xiayu Rao, Yu Li, Spencer C. Wei, Yang Zhao, The University of Texas M.D. Anderson Cancer Center [Houston], Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Epidemiology in Dermatology and Evaluation in Therapeutics (EpiDermE), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Heidelberg University Hospital [Heidelberg], Hospices Civils de Lyon (HCL), Service de Pharmacologie médicale [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), University of Texas at Austin [Austin], Service de pharmacologie médicale [CHU Pitié-Salpêtrière], 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 Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), and Institut National des Sciences Appliquées (INSA)-Université de Lyon-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)
Subjects: 0301 basic medicine, cardio-oncology, Fulminant, Immune checkpoint inhibitors, [SDV]Life Sciences [q-bio], Mechanism based, Electrocardiography, Mice, 0302 clinical medicine, Neoplasms, Medicine, Molecular Targeted Therapy, Clinical syndrome, Immune Checkpoint Inhibitors, ComputingMilieux_MISCELLANEOUS, immune- related adverse events, autoimmunity, Disease Management, 3. Good health, Oncology, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Disease Susceptibility, medicine.drug, Myocarditis, Cancer therapy, chemical and pharmacologic phenomena, Article, 03 medical and health sciences, Ctla4, PD -1, Biomarkers, Tumor, Animals, Humans, Adverse effect, negative costimulation, business.industry, Abatacept, T cell, medicine.disease, Cardiotoxicity, haploinsufficiency, Disease Models, Animal, 030104 developmental biology, Immunology, Pdcd1, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, CTLA-4, myocarditis, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Immune checkpoint inhibitors (ICI) targeting CTLA4 or PD-1/PD-L1 have transformed cancer therapy but are associated with immune-related adverse events, including myocarditis. Here, we report a robust preclinical mouse model of ICI-associated myocarditis in which monoallelic loss of Ctla4 in the context of complete genetic absence of Pdcd1 leads to premature death in approximately half of mice. Premature death results from myocardial infiltration by T cells and macrophages and severe ECG abnormalities, closely recapitulating the clinical and pathologic hallmarks of ICI-associated myocarditis observed in patients. Using this model, we show that Ctla4 and Pdcd1 functionally interact in a gene dosage–dependent manner, providing a mechanism by which myocarditis arises with increased frequency in the setting of combination ICI therapy. We demonstrate that intervention with CTLA4–Ig (abatacept) is sufficient to ameliorate disease progression and additionally provide a case series of patients in which abatacept mitigates the fulminant course of ICI myocarditis. Significance: We provide a preclinical model of ICI-associated myocarditis which recapitulates this clinical syndrome. Using this model, we demonstrate that CTLA4 and PD-1 (ICI targets) functionally interact for myocarditis development and that intervention with CTLA4–Ig (abatacept) attenuates myocarditis, providing mechanistic rationale and preclinical support for therapeutic clinical studies. See related commentary by Young and Bluestone, p. 537. This article is highlighted in the In This Issue feature, p. 521
Published: 2020

30. Potential cytochrome P450-mediated pharmacokinetic interactions between herbs, food, and dietary supplements and cancer treatments

Author: Paul Gougis, Marc Hilmi, Christian Funck-Brentano, Arthur Geraud, Olivier Mir, 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), Service de Pharmacologie médicale [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 d'Oncologie médicale [CHU Pitié-Salpêtrière], Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy] (DITEP), Institut Gustave Roussy (IGR), Département interdisciplinaire d’organisation des parcours patients (DIOPP), Département de médecine oncologique [Gustave Roussy], Gestionnaire, Hal Sorbonne Université, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de pharmacologie médicale [CHU Pitié-Salpêtrière], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: 0301 basic medicine, CYP2D6, cytochromes, [SDV]Life Sciences [q-bio], Pharmacology, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, Cytochrome P-450 Enzyme System, Herb-drug interaction, Neoplasms, medicine, food-drug interaction, Animals, Cytochrome P-450 CYP3A, Humans, CYP2C8, CYP3A4, biology, business.industry, CYP1A2, Cancer, Cytochrome P450, Hematology, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Metabolic pathway, anticancer drugs, 030104 developmental biology, Cytochrome P-450 CYP2D6, 030220 oncology & carcinogenesis, oncology, Dietary Supplements, Inactivation, Metabolic, biology.protein, business, pharmacokinetics
Abstract: International audience; Herbs, food and dietary supplements (HFDS), can interact significantly with anticancer drug treatments via cytochrome p450 isoforms (CYP) CYP3A4, CYP2D6, CYP1A2, and CYP2C8. The objective of this review was to assess the influence of HFDS compounds on these cytochromes. Interactions with CYP activities were searched for 189 herbs and food products, 72 dietary supplements in Web of Knowledge® databases. Analyses were made from 140 of 3,125 clinical trials and 236 of 3,374 in vitro, animal model studies or case reports. 18 trials were found to report direct interactions between 9 HFDS with 8 anticancer drugs. 21 HFDS were found to interact with CYP3A4, a major metabolic pathway for many anticancer drugs. All 261 HFDS were classified for their interaction with the main cytochromes P450 involved in the metabolism of anticancer drugs. We provided an easy-to-use colour-coded table to easily match potential interactions between 261 HFDS and 117 anticancer drugs.
Published: 2020

31. Spontaneous reported cardiotoxicity induced by lopinavir/ritonavir in COVID-19. An alleged past-resolved problem

Author: Serena Romani, Marion Lepelley, Joe-Elie Salem, Milou Daniel Drici, Delphine Viard, Alexandre Gérard, Fanny Rocher, Audrey Fresse, CCSD, Accord Elsevier, Hôpital Pasteur [Nice] (CHU), Centre Hospitalier Universitaire [Grenoble] (CHU), Service de Pharmacologie médicale [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 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), 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), Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Service de pharmacologie médicale [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, Lopinavir/ritonavir, 030204 cardiovascular system & hematology, Cardiac arrhythmia, Drug-related side effects and adverse reactions, Lopinavir, Electrocardiography, Pharmacovigilance, 0302 clinical medicine, immune system diseases, 030212 general & internal medicine, Aged, 80 and over, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, virus diseases, Middle Aged, 3. Good health, Drug Combinations, Long QT Syndrome, Cardiology, cardiovascular system, Female, France, Cardiology and Cardiovascular Medicine, medicine.drug, medicine.medical_specialty, Long QT syndrome, QT interval, Article, 03 medical and health sciences, Internal medicine, medicine, Potassium Channel Blockers, Humans, Aged, Lopinavir-ritonavir drug combination, Cardiotoxicity, Conduction disorder, Ritonavir, business.industry, COVID-19, HIV Protease Inhibitors, medicine.disease, COVID-19 Drug Treatment, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: The antiretroviral drug lopinavir/ritonavir has been recently repurposed for the treatment of COVID-19. Its empirical use has been associated with multiple cardiac adverse reactions pertaining to its ancillary multi-channel blocking properties, vaguely characterized until now. We aimed to characterize qualitatively the cardiotoxicity associated with lopinavir/ritonavir in the setting of COVID-19. Spontaneous notifications of cardiac adverse drug reactions reported to the national Pharmacovigilance Network were collected for 8 weeks since March 1st 2020. The Nice Regional Center of Pharmacovigilance, whose scope of expertise is drug-induced long QT syndrome, analyzed the cases, including the reassessment of all available ECGs. QTc ≥ 500 ms and delta QTc > 60 ms from baseline were deemed serious. Twenty-two cases presented with 28 cardiac adverse reactions associated with the empirical use of lopinavir/ritonavir in a hospital setting. Most adverse reactions reflected lopinavir/ritonavir potency to block voltage-gated potassium channels with 5 ventricular arrhythmias and 17 QTc prolongations. An average QTc augmentation of 97 ± 69 ms was reported. Twelve QTc prolongations were deemed serious. Other cases were likely related to lopinavir/ritonavir potency to block sodium channels: 1 case of bundle branch block and 5 recurrent bradycardias. The incidence of cardiac adverse reactions of lopinavir/ritonavir was estimated between 0.3% and 0.4%. These cardiac adverse drug reactions offer a new insight in its ancillary multi-channel blocking functions. Lopinavir/ritonavir cardiotoxicity may be of concern for its empirical use during the COVID-19 pandemic. Caution should be exerted relative to this risk where lopinavir/ritonavir summary of product characteristics should be implemented accordingly., Highlights • Lopinavir/ritonavir induces cardiotoxicity in COVID-19 • Featured cardiac adverse events reflect ancillary multiple channel blocking propertiesCaution should prevail with off-label use because of its cardiotoxicity • It summary of product characteristics must signal that risk
Published: 2020

32. Anticancer drugs and cardiovascular-related hospitalization in metastatic colorectal cancer: Insights from the AVOCETTE population-based study

Author: Dolladille, Charles, Launoy, Guy, Bouvier, Véronique, Salem, Joe-Elie, Legallois, Damien, Milliez, Paul, Sassier, Marion, Lobbedez, Thierry, Guittet, Lydia, Alexandre, Joachim, Service de cardiologie et de pathologie vasculaire [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), Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pharmacologie médicale [CHU Pitié-Salpêtrière], 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), Signalisation, électrophysiologie et imagerie des lésions d’ischémie-reperfusion myocardique (SEILIRM), Normandie Université (NU)-Normandie Université (NU), Département de Pharmacologie [CHU Caen], Service de Néphrologie-Dialyse-Transplantation rénale [CHU Caen], Unité de Recherches et d'Evaluations en Epidémiologie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Caen, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pharmacologie médicale [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), 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), 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), and HAL-SU, Gestionnaire
Subjects: metastatic colorectal cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, anticancer drugs, cardiovascular events, population based-registry, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, cardiovascular system, antineoplastic agents, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, all-cause mortality, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract: International audience; We aimed to investigate the association between anticancer drugs and cardiovascular-related hospitalization (CVRH) in metastatic colorectal cancer (mCRC) patients. A cohort study was conducted using the French county Calvados registry of digestive tumors. Incident mCRC cases between 2008 and 2014 were included. The follow-up end date was December 2016. Data from the county hospital center pharmacy and medical information departments were matched with the registry data. A competing risk approach was used. Statistical tests were two-sided. A total of 1,116 mCRC patients were included; they were administered 12,374 rounds of treatment; fluorouracil, oxaliplatin, irinotecan and bevacizumab were most common. A total of 208 CVRH events occurred in 145 patients (13.0%). The International Cancer Survival Standards type 1 standardized incidence was 84.0 CVRH per 1,000 person-years (95% confidence interval: 72.6-95.5). Anticancer drugs were not associated with a higher incidence of CVRH. Men, elderly patients, patients with a prior history of CVRH and patients with a higher Charlson comorbidity index were associated with a higher incidence of CVRH. CVRH was significantly associated with a higher all-cause mortality (multivariable hazard ratio for death 1.58, 95%CI 1.28-1.95). Anticancer drugs were not associated with a higher incidence of CVRH in mCRC patients.
Published: 2020

33. Proteomic analysis of bystander effects in chondrosarcoma cells

Author: Gilbert, Antoine, Tudor, Mihaela, Lepleux, Charlotte, Rofidal, V., Hem, Sonia, Almunia, Christine, Armengaud, J., Brotin, Emilie, Haghdoost, Siamak, Savu, Diana, Chevalier, François, Accueil et Recherche en Radiobiologie des Ions Accélérés (ARIA), Centre de recherche sur les Ions, les MAtériaux et la Photonique (CIMAP - UMR 6252), Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU), Unité de Recherche Protéomique (PROTEOMIQUE), Institut National de la Recherche Agronomique (INRA), Plateforme de Spectrométrie de Masse Protéomique - Mass Spectrometry Proteomics Platform (MSPP), Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Innovations technologiques pour la Détection et le Diagnostic (LI2D), Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Médicaments et Technologies pour la Santé (MTS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Pharmacologie et d'Immunoanalyse (SPI), Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Department of Life and Environmental Physics [Magurele, Roumanie], Horia Hulubei National Institute of Physics and Nuclear Engineering [Magurele, Roumanie], Lund University, Swedish Radiobiological Society, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche sur les Matériaux Avancés (IRMA), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), and Chevalier, Francois
Subjects: [SDV.CAN] Life Sciences [q-bio]/Cancer, [PHYS.PHYS.PHYS-BIO-PH] Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, ComputingMilieux_MISCELLANEOUS
Abstract: Numéro de Poster : P25; International audience
Published: 2020

34. Cardiovascular Toxicity Related to Cancer Treatment: A Pragmatic Approach to the American and European Cardio-Oncology Guidelines

Author: Charles Dolladille, Aude Charbonnier, Franck Thuny, Mariana Mirabel, Stéphane Champiat, Alain Cohen-Solal, Joe-Elie Salem, Joachim Alexandre, Laure Farnault, Ariel Cohen, Stéphane Ederhy, Fabrice Barlesi, Ghandi Damaj, Jennifer Cautela, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Aix Marseille Université (AMU), Sorbonne Université (SU), Université Paris-Saclay, Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Fédération Française de Cardiologie, Service de cardiologie et de pathologie vasculaire [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), Département de Pharmacologie [CHU Caen], Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Assistance Publique - Hôpitaux de Marseille (APHM), Service de Cardiologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Thrombose, atherothrombose et pharmacologie appliquée, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Hématologie Biologique [CHU Caen], Service de pharmacologie médicale [CHU Pitié-Salpêtrière], 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), CIC Paris Est, 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 (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy] (DITEP), Institut Gustave Roussy (IGR), 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), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Normandie Université (NU), Hôpital Nord [CHU - APHM], Groupe Méditerranéen de Cardio-Oncologie, Partenaires INRAE, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Tenon [AP-HP], Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Aix Marseille Université (AMU), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), 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], Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Gestionnaire, Hal Sorbonne Université
Subjects: Cardiovascular toxicity, medicine.medical_specialty, cardio-oncology, INDUCED CARDIOTOXICITY, TROPONIN-I, [SDV]Life Sciences [q-bio], cardiotoxicity, ADULT SURVIVORS, [SDV.CAN]Life Sciences [q-bio]/Cancer, Antineoplastic Agents, 030204 cardiovascular system & hematology, THERAPY, 03 medical and health sciences, 0302 clinical medicine, LEFT-VENTRICULAR DYSFUNCTION, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Neoplasms, medicine, MANAGEMENT, BREAST-CANCER, Humans, cancer, guidelines, Cardio oncology, Intensive care medicine, OCCLUSIVE DISEASE, Special Report, cardio‐oncology, RISK, Cardiotoxicity, business.industry, Cancer, medicine.disease, PREVENTION, United States, 3. Good health, Cancer treatment, [SDV] Life Sciences [q-bio], Europe, Cardiovascular Diseases, 030220 oncology & carcinogenesis, Practice Guidelines as Topic, Immunotherapy, Cardiology and Cardiovascular Medicine, business
Abstract: The considerable progress made in the field of cancer treatment has led to a dramatic improvement in the prognosis of patients with cancer. However, toxicities resulting from these treatments represent a cost that can be harmful to short‐ and long‐term outcomes. Adverse events affecting the cardiovascular system are one of the greatest challenges in the overall management of patients with cancer, as they can compromise the success of the optimal treatment against the tumor. Such adverse events are associated not only with older chemotherapy drugs such as anthracyclines but also with many targeted therapies and immunotherapies. Recognizing this concern, several American and European governing societies in oncology and cardiology have published guidelines on the cardiovascular monitoring of patients receiving potentially cardiotoxic cancer therapies, as well as on the management of cardiovascular toxicities. However, the low level of evidence supporting these guidelines has led to numerous discrepancies, leaving clinicians without a consensus strategy to apply. A cardio‐oncology expert panel from the French Working Group of Cardio‐Oncology has undertaken an ambitious effort to analyze and harmonize the most recent American and European guidelines to propose roadmaps and decision algorithms that would be easy for clinicians to use in their daily practice. In this statement, the experts addressed the cardiovascular monitoring strategies for the cancer drugs associated with the highest risk of cardiovascular toxicities, as well as the management of such toxicities.
Published: 2020

35. HIV Infection and Long-Term Residual Cardiovascular Risk After Acute Coronary Syndrome

Author: Franck Boccara, Murielle Mary‐Krause, Valérie Potard, Emmanuel Teiger, Sylvie Lang, Nadjib Hammoudi, Marion Chauvet, Stéphane Ederhy, Laurie Dufour‐Soulat, Yann Ancedy, Pascal Nhan, Saroumadi Adavane, Ph. Gabriel Steg, Christian Funck‐Brentano, Dominique Costagliola, Ariel Cohen, S. Weber, K. Wahbi, P. Beaufils, P. Henri, G. Sideris, D. Thomas, G. Montalescot, F. Beygui, C. Meuleman, S. Janower, F. Raoux, G. Dufaitre, N. Benyounes, P. L. Michel, B. Petillon, N. Hammoudi, P. Gueret, J. L. Dubois‐Rande, E. Teiger, P. Lim, M. Slama, P. Colin, C. Saudubray, O. Dubourg, O. Milleron, B. Gallet, F. Duclos, S. Godard, L. Fuchs, V. Dormagen, P. Lewy, S. Cattan, O. Nallet, G. Grollier, J. Shayne, J. E. Wolf, Y. Cottin, J. Machecourt, H. Bouvaist, G. Finet, B. De Breyne, J. N. Trochu, M. Baudouy, E. Ferrari, M. Benhamou, J. Allal, D. Coisne, H. Le Breton, M. Bedossa, J. Puel, M. Elbaz, L. Larifla, S. Matheron, R. Landman, G. Fremont, G. Spiridon, P. Blanche, J. P. Morini, D. Sicard, V. Zeller, D. Batisse, P. Clevenbergh, G. Cessot, E. Dohin, M. A. Valantin, S. Khelifa, P. M. Girard, F. Lallemand, B. Lefebvre, J. P. Laporte, J. L. Meynard, H. Bideault, O. Picard, M. C. Meyohas, P. Campa, J. Tredup, L. Fonquernie, G. Raguin, J. M. Molina, A. Furco, S. Gharakanian, J. P. Vincensini, J. B. Guiard‐Schmid, G. Pialoux, B. Cardon, A. S. Lascaux, F. Chaix, P. Lesprit, R. Fior, F. Boue, C. Dupont, C. Bellier, A. Blanc, T. Lambert, T. Touahri, G. Force, P. de Truchis, M. A. Compagnucci‐Seguenot, I. Cahitte, L. Roudière, M. E. Techer, P. Thelpin, D. Troisvallets, A. Lepretre, M. Echard, Y. Le Mercier, D. Houlbert, S. Dargere, C. Bazin, R. Verdon, B. De Goer, M. Duong, P. Chavanet, E. Gozlan, P. Leclercq, F. Brunel‐Dal Mas, J. Durant, P. Heudier, C. Brunet‐François, G. Le Moal, J. M. Chapplin, C. Arvieux, G. Chaumentin, B. Guerin, E. Bonnet, Y. Poinsignon, F. Boulard, I. De Lacroix, M. T. Goerger‐Sow, M. Kirstetter, M. Volstein, F. Laylavoix, X. Copin, C. Ceppi, Service de Cardiologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Henri Mondor, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre d'Investigation Clinique Henri Mondor (CIC Henri Mondor), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, CIC Paris Est, Service de pharmacologie médicale [CHU Pitié-Salpêtrière], 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), 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), 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 [IHU 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Centre d'investigation clinique Paris Est (CIC Paris-Est), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Service de Pharmacologie médicale [CHU Pitié-Salpêtrière]
Subjects: Male, Heart disease, [SDV]Life Sciences [q-bio], Human immunodeficiency virus (HIV), Aftercare, heart failure, HIV Infections, heart disease, 030204 cardiovascular system & hematology, medicine.disease_cause, Coronary artery disease, 0302 clinical medicine, prevention, Recurrence, Risk Factors, Cardiovascular Disease, Secondary Prevention, Medicine, 030212 general & internal medicine, Longitudinal Studies, Prospective Studies, Original Research, Middle Aged, Prognosis, 3. Good health, Editorial, myocardial infarction, Anti-Retroviral Agents, Cardiovascular Diseases, Cardiology, Female, France, Cardiology and Cardiovascular Medicine, coronary artery disease, Adult, Acute coronary syndrome, medicine.medical_specialty, 03 medical and health sciences, Percutaneous Coronary Intervention, Internal medicine, Humans, Acute Coronary Syndrome, business.industry, dyslipidemia, Coronary Care Units, Editorials, HIV, medicine.disease, HIV infection, Cerebrovascular Disorders, Heart Disease Risk Factors, Case-Control Studies, ST Elevation Myocardial Infarction, business, Dyslipidemia
Abstract: Background It is unclear whether HIV infection affects the long‐term prognosis after an acute coronary syndrome (ACS). The objective of the current study was to compare rates of major adverse cardiac and cerebrovascular events after a first ACS between people living with HIV (PLHIV) and HIV‐uninfected (HIV−) patients, and to identify determinants of cardiovascular prognosis. Methods and Results Consecutive PLHIV and matched HIV− patients with a first episode of ACS were enrolled in 23 coronary intensive care units in France. Patients were matched for age, sex, and ACS type. The primary end point was major adverse cardiac and cerebrovascular events (cardiac death, recurrent ACS, recurrent coronary revascularization, and stroke) at 36‐month follow‐up. A total of 103 PLHIV and 195 HIV− patients (mean age, 49 years [SD, 9 years]; 94.0% men) were included. After a mean of 36.6 months (SD, 6.1 months) of follow‐up, the risk of major adverse cardiac and cerebrovascular events was not statistically significant between PLHIV and HIV− patients (17.8% and 15.1%, P =0.22; multivariable hazard ratio [HR], 1.60; 95% CI, 0.67–3.82 [ P =0.29]). Recurrence of ACS was more frequent among PLHIV (multivariable HR, 6.31; 95% CI, 1.32–30.21 [ P =0.02]). Stratified multivariable Cox models showed that HIV infection was the only independent predictor for ACS recurrence. PLHIV were less likely to stop smoking (47% versus 75%; P =0.01) and had smaller total cholesterol decreases (–22.3 versus –35.0 mg/dL; P =0.04). Conclusions Although the overall risk of major adverse cardiac and cerebrovascular events was not statistically significant between PLHIV and HIV− individuals, PLHIV had a higher rate of recurrent ACS. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00139958.
Published: 2020

36. Drug-induced IgA vasculitis in children and adults: Revisiting drug causality using a dual pharmacovigilance-based approach

Author: Julie Garon-Czmil, Camille Rasmussen, Joe-Elie Salem, Loïc Guillevin, Benjamin Terrier, Laurent Chouchana, Mylène Tisseyre, Marina Atzenhoffer, Jean-Marc Treluyer, Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de Pharmacologie Clinique [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Pharmacologie Clinique et Toxicologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hospices Civils de Lyon (HCL), Service de pharmacologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: 0301 basic medicine, Drug, Adult, Male, Vasculitis, medicine.medical_specialty, Henoch-Schonlein purpura, IgA Vasculitis, media_common.quotation_subject, Immunology, Culprit, 03 medical and health sciences, Pharmacovigilance, 0302 clinical medicine, Antibiotics, Psoriasis, Internal medicine, medicine, Immunology and Allergy, Humans, TNFα blockers, Child, media_common, 030203 arthritis & rheumatology, Vaccines, business.industry, Middle Aged, medicine.disease, 3. Good health, Immunoglobulin A, 030104 developmental biology, IgA vasculitis, Pharmaceutical Preparations, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Etiology, business
Abstract: Objectives IgA vasculitis (IgAV) is an immune complex small-vessel vasculitis. Drug-induced IgAV cases were rarely reported in the literature. Drug causality assessment is challenging as many other etiological factors can be involved. We performed a pharmacovigilance study to identify the main drugs reported to induce IgAV. Methods We used the French pharmacovigilance database (FPVD) and the WHO global individual case safety reports database (VigiBase) to retrieve IgAV cases. Cases from the FPVD were reviewed by two investigators using predefined criteria. Disproportionality analyses (case – non-case approach) were conducted in VigiBase to identify drugs significantly associated with IgAV reporting. Results Of the 467 IgAV cases retrieved from the FPVD, 115 (47 children and 68 adults) have been assessed as definite or probable, reported with 178 suspected drugs. Overall IgAV cases were mainly male (58%), with a median age of 33.5 (8.0–63.3) years. No death was reported. Besides, we identified 1558 possible IgAV cases in VigiBase. Among them, 40 were associated with a disproportionality in IgAV reporting. Drugs were mainly vaccines, antibiotics and TNF-α blockers, these finding being consistent in both databases. IgAV reporting with TNF-α blockers was significantly associated with their use in inflammatory bowel diseases, psoriasis or ankylosing spondylitis compared to other indications. Conclusions Our systematic study enables the identification of culprit drugs in drug-induced IgAV. These results strengthen the immune pathophysiology of IgAV and the role of underlying disease. The list of suspected drugs may be useful for physicians to manage patients with IgAV and consider appropriate drug discontinuation. Key messages What is already known about this subject? IgA vasculitis has multifactorial etiology. To date, possible culprit drugs have been reported only in case reports. What does this study add? Using a dual pharmacovigilance-based approach, we identified drugs associated with the occurrence of IgA vasculitis, such as all types of vaccines, major antibiotics and immunomodulatory agents, mainly TNF-α blockers. How might this impact on clinical practice or future developments? Physicians should be aware of drug-induced IgA vasculitis and we provide evidence on the most frequent implicated drugs.
Published: 2020

37. Immune Checkpoint Inhibitor‐Associated Primary Adrenal Insufficiency: WHO VigiBase Report Analysis

Author: Melissa Y.Y. Moey, Joe-Elie Salem, Bénédicte Lebrun-Vignes, Javid Moslehi, Virginie Grouthier, Anne Bachelot, Douglas B. Johnson, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service de pharmacologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Epidemiology in Dermatology and Evaluation in Therapeutics (EpiDermE), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de référence des maladies endocriniennes rares de la croissance et du développement [CHU Pitié-Salpêtrière], Service de Pharmacologie médicale [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), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU 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), 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), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), and Gestionnaire, Hal Sorbonne Université
Subjects: Adult, Male, Cancer Research, medicine.medical_specialty, [SDV]Life Sciences [q-bio], 030209 endocrinology & metabolism, Ipilimumab, Pembrolizumab, World Health Organization, Primary Adrenal Insufficiency, 03 medical and health sciences, Immune checkpoint inhibitors, Antineoplastic Agents, Immunological, 0302 clinical medicine, Addison Disease, Immune-related adverse events, Internal medicine, Pharmacovigilance, medicine, Adrenal insufficiency, Humans, Adverse effect, Aged, Aged, 80 and over, business.industry, Endocrine toxicity, Middle Aged, medicine.disease, Immuno‐Oncology, 3. Good health, [SDV] Life Sciences [q-bio], Clinical trial, Oncology, 030220 oncology & carcinogenesis, Immunotherapy, Nivolumab, Primary adrenal insufficiency, business, Adrenal Insufficiency, medicine.drug
Abstract: Background Immune checkpoint inhibitors (ICIs) have transformed cancer therapy but may also trigger autoimmune adverse drug reactions (ADRs) referred to as immune-related adverse events (irAEs). Although endocrinopathies are among the most common form of irAEs, primary adrenal insufficiency (PAI) is infrequent and has only been published in case reports. The aim of this study was to identify and characterize the main features of PAI-irAE. Materials and Methods Suspected PAI-irAE cases were identified using VigiBase, the World Health Organization's pharmacovigilance database of individual case safety reports. Results From September 2, 2008, through October 5, 2018, a total of 50,108 ICI-associated ADRs were reported. Since 2008, there were 451 cases of PAI-irAE identified of which 45 were “definite PAI” and 406 “possible PAI.” Patients were mainly male (58.1%) with a median age of 66 years (range, 30–95). Indications of ICI were predominantly for melanoma (41.2%) and lung cancer (28.6%). The majority of patients were treated with ICI monotherapy (nivolumab: 44.3%, pembrolizumab: 11.7%, ipilimumab: 23.6%), and 17.9% were treated with ICI combination therapy. These events occurred with a median time to onset of 120 days (range, 6–576). ICI-associated PAI was associated with significant morbidity (≥90% severe) and mortality (7.3%). Fatality rates were similar in the subgroups of combination therapy versus monotherapy. There were no relevant differences in clinical or demographical characteristics and outcomes between “definite” versus “possible” PAI group. Conclusion Our study represents the largest clinical description and characterization of PAI-irAE. Although ICI-associated PAI is a rare adverse event, early recognition is important to implement corticosteroid treatment. Further studies are required to elucidate risk factors and reversibility of this rare but severe irAE. Clinical trial identification number. NCT03492242 Implications for Practice Immune checkpoint inhibitor (ICI)-associated primary adrenal insufficiency (PAI) is a rare adverse event that is important to recognize because it may be severe and life-threatening, requiring emergent and often lifelong hormonal replacement therapy. Awareness regarding this ICI-related endocrinopathy is strongly encouraged among clinicians in addition to patient education about common PAI symptoms that should prompt urgent medical evaluation. In clinical practice, close monitoring and investigation for PAI is crucial to allow for early management and to further define the pathophysiology and prognosis of ICI-PAI. Corticotrophin (adrenocorticotrophic hormone) circulating level evaluation may be often lacking but should be considered as part of the diagnostic workup to differentiate PAI from secondary (central) adrenal insufficiency.
Published: 2020

38. The quality of reporting general safety parameters and immune-related adverse events in clinical trials of FDA-approved immune checkpoint inhibitors

Author: Agnès Dechartres, Florence Tubach, Zahra Karimian, Joe-Elie Salem, Sandra Mavoungou, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université - Département de santé publique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'investigation clinique Neurosciences [CHU Pitié Salpêtrière] (CIC Neurosciences), 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), CIC Paris Est, 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], Service de pharmacologie médicale [CHU Pitié-Salpêtrière], Service de Cardiologie [CHU Pitié-Salpêtrière], Gestionnaire, Hal Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), 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)-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 d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), and Service de Pharmacologie médicale [CHU Pitié-Salpêtrière]
Subjects: Cancer Research, medicine.medical_specialty, media_common.quotation_subject, Immune checkpoint inhibitors, [SDV]Life Sciences [q-bio], law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Immune-related adverse events, Genetics, Medicine, Adverse Drug Reaction Reporting Systems, Humans, Quality (business), 030212 general & internal medicine, Intensive care medicine, Adverse effect, media_common, business.industry, Serious adverse events, 3. Good health, [SDV] Life Sciences [q-bio], Clinical trial, Systematic review, Oncology, Reporting, 030220 oncology & carcinogenesis, Randomized controlled trials, Immunotherapy, Safety, business, Research Article
Abstract: BackgroundWhile immune-checkpoint inhibitors (ICIs) have transformed the field of oncology for advanced-stage cancers, they can lead to serious immune toxicities. Several systematic reviews have evaluated the risk of immune-related adverse events (irAEs); however, most have focused on published articles without evaluating trial registries. The objective of this methodological review was to compare the quality of reporting of safety information and in particular, serious irAEs (irSAEs), in both publications andClinicalTrials.govfor all current FDA-approved ICIs.MethodsPubMed was searched to retrieve all published phase III randomized controlled trials (RCTs) evaluating ICIs. For each eligible trial, we searched for corresponding registration onClinicalTrials.govand extracted relevant safety data from both the publication and results posted on registry. We then compared the quality of reporting and the value of safety data between both sources.ResultsOf 42 eligible published trials, 34 had results posted onClinicalTrials.gov. Considerable variability was noted in the reporting of safety in both sources. SAEs were reported for all trial results inClinicalTrials.govcompared to 23.5% of publications. An overall incidence for irAEs and irSAEs was reported in 58.8 and 8.8% of publications respectively, compared to 11.8 and 5.9% in registry results. Comparing the value of specific irSAEs was not possible between the two sources in 32/34 trials either due to different reporting formats (61.8%) or data not being reported in one or both sources (32.4%). From the 2 studies with compatible irSAE format, only 1 had matching data in both sources.ConclusionsThe reporting of irAEs / irSAEs varies considerably in publications and registries, which outlines the importance of standardizing the terminologies and methodologies for reporting safety information relevant to ICIs.
Published: 2020

39. Resilient and Sensitive Key Points of the Photosynthetic Machinery of Coffea spp. to the Single and Superimposed Exposure to Severe Drought and Heat Stresses

Author: Danielly Dubberstein, Fernando C. Lidon, Ana P. Rodrigues, José N. Semedo, Isabel Marques, Weverton P. Rodrigues, Duarte Gouveia, Jean Armengaud, Magda C. Semedo, Sónia Martins, Maria C. Simões-Costa, I. Moura, Isabel P. Pais, Paula Scotti-Campos, Fábio L. Partelli, Eliemar Campostrini, Ana I. Ribeiro-Barros, Fábio M. DaMatta, José C. Ramalho, GeoBioTec - Geobiociências, Geoengenharias e Geotecnologias, Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Pharmacologie et d'Immunoanalyse (SPI), and Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay
Subjects: 0106 biological sciences, 0301 basic medicine, Photoinhibition, Drought tolerance, coffee, drought, Plant Science, lcsh:Plant culture, acclimation, Photosynthesis, 01 natural sciences, Acclimatization, 03 medical and health sciences, SDG 13 - Climate Action, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, lcsh:SB1-1110, Photosystem, 2. Zero hunger, photosynthesis, biology, photoinhibition, Chemistry, AMAX, RuBisCO, food and beverages, 15. Life on land, Chloroplast, Horticulture, 030104 developmental biology, climate change, 13. Climate action, biology.protein, heat, 010606 plant biology & botany
Abstract: No 727934 PTDC/ASP-AGR/31257/2017 UIDB/00239/2020 UIDP/04035/2020 E-26/202.323/2017 This study unveils the single and combined drought and heat impacts on the photosynthetic performance of Coffea arabica cv. Icatu and C. canephora cv. Conilon Clone 153 (CL153). Well-watered (WW) potted plants were gradually submitted to severe water deficit (SWD) along 20 days under adequate temperature (25/20°C, day/night), and thereafter exposed to a gradual temperature rise up to 42/30°C, followed by a 14-day water and temperature recovery. Single drought affected all gas exchanges (including Amax) and most fluorescence parameters in both genotypes. However, Icatu maintained Fv/Fm and RuBisCO activity, and reinforced electron transport rates, carrier contents, and proton gradient regulation (PGR5) and chloroplast NADH dehydrogenase-like (NDH) complex proteins abundance. This suggested negligible non-stomatal limitations of photosynthesis that were accompanied by a triggering of protective cyclic electron transport (CEF) involving both photosystems (PSs). These findings contrasted with declines in RuBisCO and PSs activities, and cytochromes (b559, f, b563) contents in CL153. Remarkable heat tolerance in potential photosynthetic functioning was detected in WW plants of both genotypes (up to 37/28°C or 39/30°C), likely associated with CEF in Icatu. Yet, at 42/30°C the tolerance limit was exceeded. Reduced Amax and increased Ci values reflected non-stomatal limitations of photosynthesis, agreeing with impairments in energy capture (F0 rise), PSII photochemical efficiency, and RuBisCO and Ru5PK activities. In contrast to PSs activities and electron carrier contents, enzyme activities were highly heat sensitive. Until 37/28°C, stresses interaction was largely absent, and drought played the major role in constraining photosynthesis functioning. Harsher conditions (SWD, 42/30°C) exacerbated impairments to PSs, enzymes, and electron carriers, but uncontrolled energy dissipation was mitigated by photoprotective mechanisms. Most parameters recovered fully between 4 and 14 days after stress relief in both genotypes, although some aftereffects persisted in SWD plants. Icatu was more drought tolerant, with WW and SWD plants usually showing a faster and/or greater recovery than CL153. Heat affected both genotypes mostly at 42/30°C, especially in SWD and Icatu plants. Overall, photochemical components were highly tolerant to heat and to stress interaction in contrast to enzymes that deserve special attention by breeding programs to increase coffee sustainability in climate change scenarios. publishersversion published
Published: 2020

40. Demographic Factors Associated with Toxicity in Patients Treated with Anti–Programmed Cell Death-1 Therapy

Author: Kaustav P. Shah, Javid Moslehi, Douglas B. Johnson, Haocan Song, Fei Ye, Justin M. Balko, Joe-Elie Salem, Vanderbilt University School of Medicine [Nashville], Service de pharmacologie médicale [CHU Pitié-Salpêtrière], 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), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Gestionnaire, Hal Sorbonne Université, Service de Pharmacologie médicale [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), 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), 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], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Adult, Male, 0301 basic medicine, Cancer Research, medicine.medical_specialty, Myocarditis, Adolescent, [SDV]Life Sciences [q-bio], Programmed Cell Death 1 Receptor, Immunology, Ipilimumab, Article, Young Adult, 03 medical and health sciences, Antineoplastic Agents, Immunological, 0302 clinical medicine, Risk Factors, Internal medicine, Pharmacovigilance, medicine, Humans, Immunologic Factors, CTLA-4 Antigen, Young adult, Adverse effect, Melanoma, Aged, Pneumonitis, Aged, 80 and over, Hepatitis, business.industry, Age Factors, Length of Stay, Middle Aged, medicine.disease, 3. Good health, Hospitalization, [SDV] Life Sciences [q-bio], 030104 developmental biology, 030220 oncology & carcinogenesis, Female, Immunotherapy, Nivolumab, business, medicine.drug
Abstract: Immune checkpoint inhibitors (ICI) are now routinely used in multiple cancers but may induce autoimmune-like side effects known as immune-related adverse events (irAE). Although classical autoimmune diseases have well-known risk factors, including age, gender, and seasonality, the clinical factors that lead to irAEs are not well-defined. To explore these questions, we assessed 455 patients with advanced melanoma treated with ICI at our center and a large pharmacovigilance database (VigiBase). We found that younger age was associated with a similar rate of any irAEs but more frequent severe irAEs and more hospitalizations (OR, 0.97 per year). Paradoxically, however, older patients had more deaths and increased length of stay (LOS) when hospitalized. This was partially due to a distinct toxicity profile: Colitis and hepatitis were more common in younger patients, whereas myocarditis and pneumonitis had an older age distribution both in our center and in VigiBase. This pattern was particularly apparent with combination checkpoint blockade with ipilimumab and nivolumab. We did not find a link between gender or seasonality on development of irAEs in univariate or multivariate analyses, although winter hospitalizations were associated with marginally increased LOS. This study identifies age-specific associations of irAEs.
Published: 2020

41. Retraction and republication: cardiac toxicity of hydroxychloroquine in COVID-19

Author: Christian Funck-Brentano, Joe-Elie Salem, Lee S. Nguyen, Service de pharmacologie médicale [CHU Pitié-Salpêtrière], 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), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Gestionnaire, Hal Sorbonne Université, Service de Pharmacologie médicale [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), 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), 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], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: 2019-20 coronavirus outbreak, Cardiotoxicity, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV]Life Sciences [q-bio], Hydroxychloroquine, General Medicine, 030204 cardiovascular system & hematology, Virology, Article, 3. Good health, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, Cardiac toxicity, medicine, 030212 general & internal medicine, business, Coronavirus Infections, ComputingMilieux_MISCELLANEOUS, medicine.drug
Abstract: International audience
Published: 2020

42. Anticancer drugs and COVID-19 antiviral treatments in patients with cancer: What can we safely use?

Author: Charlotte Fenioux, Caroline Solas, Jean Philippe Spano, Joseph Gligorov, Christian Funck-Brentano, Marianne Veyri, Paul Gougis, Service de pharmacologie médicale [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 Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service d'Oncologie médicale [CHU Tenon], CHU Tenon [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), Assistance Publique - Hôpitaux de Marseille (APHM), Service d'Oncologie médicale [CHU Pitié-Salpêtrière], Gestionnaire, HAL Sorbonne Université 5, Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: 0301 basic medicine, Cancer Research, Pharmacology, Poly (ADP-Ribose) Polymerase Inhibitor, Lopinavir, 0302 clinical medicine, Antineoplastic Agents, Immunological, Cytochrome P-450 Enzyme System, Neoplasms, Drug Interactions, ComputingMilieux_MISCELLANEOUS, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 3. Good health, Drug Combinations, Long QT Syndrome, Oncology, 030220 oncology & carcinogenesis, Pyrazines, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Kidney Diseases, Chemical and Drug Induced Liver Injury, Coronavirus Infections, Proteasome Inhibitors, Hydroxychloroquine, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Antineoplastic Agents, Hormonal, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Pneumonia, Viral, [SDV.CAN]Life Sciences [q-bio]/Cancer, Antineoplastic Agents, Poly(ADP-ribose) Polymerase Inhibitors, Antibodies, Monoclonal, Humanized, Anticancer drugs, Antiviral Agents, Article, 03 medical and health sciences, Betacoronavirus, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Drug-induced long QT syndrome, Humans, In patient, Antiviral interactions, Pandemics, Protein Kinase Inhibitors, Immunosuppression Therapy, Ritonavir, business.industry, SARS-CoV-2, Cancer, COVID-19, medicine.disease, Amides, COVID-19 Drug Treatment, Histone Deacetylase Inhibitors, 030104 developmental biology, business
Abstract: Highlights • More safety data is needed to treat COVID-19 symptomatic patients with anticancer drugs known to increase infections. • We summarized immunosuppressing anticancer drugs; other drugs were studied for drug-drug interactions with antiviral medicines. • A ready-to-use table synthetize these pharmacokinetic and pharmacodynamic interactions between antiviral and anticancer drugs.
Published: 2020

43. Response to the editorial 'COVID-19 in patients with cardiovascular diseases'

Author: Milou Daniel Drici, Joe-Elie Salem, Dan M. Roden, Christian Funck-Brentano, Lee S. Nguyen, Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], 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), 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), Unité de Soins Intensifs [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Cimiez [Nice] (CHU), Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Gestionnaire, Hal Sorbonne Université, Service de pharmacologie médicale [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CIC Paris Est, 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 (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN)
Subjects: medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Potential risk, business.industry, Long QT syndrome, [SDV]Life Sciences [q-bio], Torsades de pointes, Hydroxychloroquine, General Medicine, 030204 cardiovascular system & hematology, medicine.disease, Azithromycin, 030226 pharmacology & pharmacy, 3. Good health, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, Chloroquine, Internal medicine, medicine, In patient, business, Cardiology and Cardiovascular Medicine, ComputingMilieux_MISCELLANEOUS, medicine.drug
Abstract: International audience
Published: 2020

44. Chloroquine or hydroxychloroquine for COVID-19: why might they be hazardous?

Author: Funck-Brentano, Christian, Salem, Joe-Elie, Service de pharmacologie médicale [CHU Pitié-Salpêtrière], 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), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Gestionnaire, Hal Sorbonne Université, Service de Pharmacologie médicale [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), 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), 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], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2020

45. Acute Coronary Syndrome With Immune Checkpoint Inhibitors: A Proof-of-Concept Case and Pharmacovigilance Analysis of a Life-Threatening Adverse Event

Author: Charles Dolladille, Franck Thuny, Franck Paganelli, Ugo Scemama, Ariel Cohen, Franck Rouby, Joachim Alexandre, Stéphane Ederhy, Joe-Elie Salem, Jennifer Cautela, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Nord [CHU - APHM], Centre régional de pharmacovigilance de Marseille Provence Corse [CHU de Marseille] (CRPV-Marseille), CHU Marseille-Assistance Publique-Hôpitaux de Marseille (AP-HM), Service de pharmacologie médicale [CHU Pitié-Salpêtrière], 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), CIC Paris Est, 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 (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Département de Pharmacologie [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), Signalisation, électrophysiologie et imagerie des lésions d’ischémie-reperfusion myocardique (SEILIRM), Normandie Université (NU)-Normandie Université (NU), Thrombose, atherothrombose et pharmacologie appliquée, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille, Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de Pharmacologie médicale [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), Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and CCSD, Accord Elsevier
Subjects: Male, medicine.medical_specialty, Acute coronary syndrome, Immune checkpoint inhibitors, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Proof of Concept Study, Pharmacovigilance, 03 medical and health sciences, Antineoplastic Agents, Immunological, 0302 clinical medicine, medicine, Humans, Immunologic Factors, 030212 general & internal medicine, Acute Coronary Syndrome, Intensive care medicine, Adverse effect, Aged, Aged, 80 and over, business.industry, Middle Aged, medicine.disease, Causality, Thrombosis, 3. Good health, [SDV] Life Sciences [q-bio], Female, Cardiology and Cardiovascular Medicine, business, Isolated cases
Abstract: International audience; Isolated cases of acute coronary syndrome (ACS) associated with immune checkpoint inhibitors (ICIs) have been described without the establishment of a formal cause-and-effect relationship between treatment and adverse event. We reported a case of ACS after the first administration of an ICI and with a fatal recurrence in another coronary area immediately after readministration. According to guidelines, causality was considered to be certain. Subsequently, we queried the French pharmacovigilance database and found 4 cases of ACS with coronary artery thrombosis. Causality was probable in those patients. These data suggest that ACS may be another life-threatening cardiac adverse event occurring with ICI exposure.
Published: 2020

46. Proposed BoNT/A and /B Peptide Substrates Cannot Detect Multiple Subtypes in the Endopep-MS Assay

Author: Kaitlyn Kiernan, Suzanne R. Kalb, Jakub Baudys, Dongxia Wang, François Becher, John R. Barr, Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Pharmacologie et d'Immunoanalyse (SPI), and Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay
Subjects: Botulinum Toxins, Health, Toxicology and Mutagenesis, Peptide, Toxicology, Mass Spectrometry, Article, Analytical Chemistry, Peptide substrate, 03 medical and health sciences, Limit of Detection, medicine, Humans, Environmental Chemistry, [CHIM]Chemical Sciences, Botulism, Botulinum Toxins, Type A, Protein Precursors, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Chemical Health and Safety, 030302 biochemistry & molecular biology, Enkephalins, medicine.disease, Virology, 3. Good health, chemistry, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Biological Assay, Peptides
Abstract: Botulinum neurotoxins (BoNTs) are a family of protein toxins consisting of seven known serotypes (BoNT/A—BoNT/G) and multiple subtypes within the serotypes, and all of which cause the disease botulism—a disease of great public health concern. Accurate detection of BoNTs in human clinical samples is therefore an important public health goal. To achieve this goal, our laboratory developed a mass spectrometry-based assay detecting the presence of BoNT via its enzymatic activity on a peptide substrate. Recently, publications reported the use of new peptide substrates to detect BoNT/A and /B with improved results over other peptide substrates. However, the authors did not provide results of their peptide substrate on multiple subtypes of BoNT. In this work, we describe the results of testing the new substrates with multiple BoNT/A and /B subtypes and find that the substrates cannot detect many subtypes of BoNT/A and /B.
Published: 2020

47. Cardiovascular Effects of Androgen Deprivation Therapy in Prostate Cancer: Contemporary Meta-Analyses

Author: Matthew S. Freiberg, Javid Moslehi, Jiun-Ruey Hu, Meredith S. Duncan, Joshua A. Beckman, Jonathan D. Brown, Wouter C. Meijers, Alicia K. Morgans, Joe-Elie Salem, Gestionnaire, Hal Sorbonne Université, Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Northwestern University Feinberg School of Medicine, Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Service de pharmacologie médicale [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CIC Paris Est, 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], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, Oncology, medicine.medical_specialty, Antineoplastic Agents, Hormonal, medicine.drug_class, [SDV]Life Sciences [q-bio], cardiotoxicity, gonadotropin releasing hormone agonists, androgen deprivation therapy, 030204 cardiovascular system & hematology, Cardiovascular System, Risk Assessment, Article, Androgen deprivation therapy, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Humans, Cardiotoxicity, business.industry, Prostatic Neoplasms, Androgen Antagonists, prostate cancer, medicine.disease, Androgen, 3. Good health, [SDV] Life Sciences [q-bio], Androgen receptor, Treatment Outcome, Cardiovascular Diseases, 030220 oncology & carcinogenesis, cardiooncology, Cardiology and Cardiovascular Medicine, business, Hormone
Abstract: International audience; Androgen deprivation therapy is a cornerstone of prostate cancer treatment. Pharmacological androgen deprivation includes gonadotropin-releasing hormone agonism and antagonism, androgen receptor inhibition, and CYP17 (cytochrome P450 17A1) inhibition. Studies in the past decade have raised concerns about the potential for androgen deprivation therapy to increase the risk of adverse cardiovascular events such as myocardial infarction, stroke, and cardiovascular mortality, possibly by exacerbating cardiovascular risk factors. In this review, we summarize existing data on the cardiovascular effects of androgen deprivation therapy. Among the therapies, abiraterone stands out for increasing risk of cardiac events in meta-analyses of both randomized controlled trials and observational studies. We find a divergence between observational studies, which show consistent positive associations between androgen deprivation therapy use and cardiovascular disease, and randomized controlled trials, which do not show these associations reproducibly.
Published: 2020

48. Top-Down and Bottom-Up Proteomics of Circulating S100A8/S100A9 in Plasma of Septic Shock Patients

Author: Nathalie Morel, Didier Payen, Christophe Junot, Stéphanie Simon, François Becher, Christelle Dubois, François Fenaille, Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Pharmacologie et d'Immunoanalyse (SPI), and Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay
Subjects: Proteomics, 0301 basic medicine, Oncology, medicine.medical_specialty, Absolute quantification, Structural diversity, Biochemistry, S100A9, S100A8, bottom-up, Sepsis, 03 medical and health sciences, S100A8/S100A9, Internal medicine, medicine, Calgranulin B, Humans, Calgranulin A, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030102 biochemistry & molecular biology, Septic shock, business.industry, General Chemistry, medicine.disease, Shock, Septic, 3. Good health, 030104 developmental biology, top-down, Biomarker (medicine), biomarker, septic shock, prognosis, business, complex
Abstract: International audience; Well-characterized prognostic biomarkers and reliable quantitative methods are key in sepsis management. Among damage-associated molecular patterns, S100A8/S100A9 complexes are reported to be markers for injured cells and to improve the prediction of death in septic shock patients. In view of the structural diversity observed for the intracellular forms, insight into circulating complexes and proteoforms is required to establish prognostic biomarkers. Here, we developed top-down and bottom-up proteomics to characterize the association of S100A8 and S100A9 in complexes and major circulating proteoforms. An antibody-free method was developed for absolute quantification of S100A8/S100A9 in a cohort of 49 patients to evaluate the prognostic value on the first day after admission for septic shock. The predominant circulating forms identified by top-down proteomics were S100A8, mono-oxidized S100A8, truncated acetylated S100A9, and S-nitrosylated S100A9. S100A8, truncated acetylated S100A9, and mono-oxidized S100A8 discriminated between survivors and nonsurvivors, along with total S100A8/S100A9 measured by the antibody-free bottom-up method. Overall, new insights into circulating S100A8/S100A9 and confirmation of its prognostic value in septic shock are crucial in qualification of this biomarker. Also, the simple antibody-free assay would support the harmonization of S100A8/S100A9 measurements.
Published: 2020

49. Deep Mutational Scan of an SCN5A Voltage Sensor

Author: Tiffany Shields, Kenneth A. Matreyek, Brett M. Kroncke, Yuko Wada, Dan M. Roden, Douglas M. Fowler, Andrew M. Glazer, Joe-Elie Salem, Tao Yang, Gestionnaire, Hal Sorbonne Université, Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], University of Washington [Seattle], Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Service de pharmacologie médicale [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CIC Paris Est, 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], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: 0301 basic medicine, Materials science, Sodium channel, Long QT syndrome, [SDV]Life Sciences [q-bio], prevalence, General Medicine, Computational biology, 030204 cardiovascular system & hematology, medicine.disease, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Voltage sensor, medicine, long QT syndrome, Brugada syndrome, Patch clamp, humans, Throughput (business), sodium channels, Ion channel
Abstract: Background: Variants in ion channel genes have classically been studied in low throughput by patch clamping. Deep mutational scanning is a complementary approach that can simultaneously assess function of thousands of variants. Methods: We have developed and validated a method to perform a deep mutational scan of variants in SCN5A , which encodes the major voltage-gated sodium channel in the heart. We created a library of nearly all possible variants in a 36 base region of SCN5A in the S4 voltage sensor of domain IV and stably integrated the library into HEK293T cells. Results: In preliminary experiments, challenge with 3 drugs (veratridine, brevetoxin, and ouabain) could discriminate wild-type channels from gain- and loss-of-function pathogenic variants. High-throughput sequencing of the pre- and postdrug challenge pools was used to count the prevalence of each variant and identify variants with abnormal function. The deep mutational scan scores identified 40 putative gain-of-function and 33 putative loss-of-function variants. For 8 of 9 variants, patch clamping data were consistent with the scores. Conclusions: These experiments demonstrate the accuracy of a high-throughput in vitro scan of SCN5A variant function, which can be used to identify deleterious variants in SCN5A and other ion channel genes.
Published: 2020

50. Exome Sequencing Reveals Signal Transduction Genes Involved in Impulse Control Disorders in Parkinson's Disease

Author: Prud'Hon, Sabine, Bekadar, Samir, Rastetter, Agnès, Guégan, Justine, Cormier-Dequaire, Florence, Lacomblez, Lucette, Mangone, Graziella, You, Hana, Daniau, Mailys, Marie, Yannick, Bertrand, Hélène, Lesage, Suzanne, Tezenas Du Montcel, Sophie, Anheim, Mathieu, Brice, Alexis, Danjou, Fabrice, Corvol, Jean-Christophe, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de pharmacologie médicale [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), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Les Hôpitaux Universitaires de Strasbourg (HUS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-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), 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), Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Gestionnaire, Hal Sorbonne Université
Subjects: Parkinson's disease (PD), Neurology, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], dopamine agonists (DA), [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], impulse control disorders (ICD), Neurology (clinical), exome sequencing, Original Research, pharmacogenetics
Abstract: International audience; Introduction: Impulse control disorders (ICDs) frequently complicate dopamine agonist (DA) therapy in Parkinson's disease (PD). There is growing evidence of a high heritability for ICDs in the general population and in PD. Variants on genes belonging to the reward pathway have been shown to account for part of this heritability. We aimed to identify new pathways associated with ICDs in PD.Methods: Thirty-six Parkinsonian patients on DA therapy with (n = 18) and without ICDs (n = 18) matched on age at PD's onset, and gender was selected to represent the most extreme phenotypes of their category. Exome sequencing was performed, and variants with a strong functional impact in brain-expressed genes were selected. Allele frequencies and their distribution in genes and pathways were analyzed with single variant and SKAT-O tests. The 10 most associated variants, genes, and pathways were retained for replication in the Parkinson's progression markers initiative (PPMI) cohort.Results: None of markers tested passed the significance threshold adjusted for multiple comparisons. However, the "Adenylate cyclase activating" pathway, one of the top associated pathways in the discovery data set (p = 1.6 × 10-3) was replicated in the PPMI cohort and was significantly associated with ICDs in a post hoc pooled analysis (combined p-value 3.3 × 10-5). Two of the 10 most associated variants belonged to genes implicated in cAMP and ERK signaling (rs34193571 in RasGRF2, p = 5 × 10-4; rs1877652 in PDE2A, p = 8 × 10-4) although non-significant after Bonferroni correction.Conclusion: Our results suggest that genes implicated in the signaling pathways linked to G protein-coupled receptors participate to genetic susceptibility to ICDs in PD.
Published: 2020

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