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1. Ernica consensus conference on the management of patients with long-gap esophageal atresia:perioperative, surgical, and long-term management

Author: Janne S. Suominen, Rene M. H. Wijnen, Paolo De Coppi, Graham Slater, Sabine Pirr, Piergiorgio Gamba, Pietro Bagolan, Stefaan H. A. J. Tytgat, Lars S. Rasmussen, Frédéric Gottrand, JoAnne Fruithof, Imeke Goldschmidt, Benno M. Ure, Joergen M. Thorup, Kate Cross, Anke Widenmann-Grolig, David C. van der Zee, Simon Eaton, Gunnar Aksnes, Wilhelm Zetterquist, Jan F. Svensson, Lucas Wessel, Carmen Dingemann, Rony Sfeir, CHU Lille, Inserm, Université de Lille, Hannover Medical School [Hannover] [MHH], University College of London [London] [UCL], Oslo University College [OUC], Bambino Gesù Children’s Hospital [Rome, Italy], Great Ormond Street Hospital for Children [London] [GOSH], Università degli Studi di Padova = University of Padua [Unipd], Lille Inflammation Research International Center (LIRIC) - U995, Odense University Hospital [OUH], Environnement Périnatal et Santé - EA 4489, University of Nottingham, UK [UON], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Karolinska University Hospital [Stockholm], University of Copenhagen = Københavns Universitet [UCPH], University Medical Center [Utrecht], University of Heidelberg, Medical Faculty, Universität Stuttgart [Stuttgart], Erasmus University Medical Center [Rotterdam] [Erasmus MC], Hannover Medical School [Hannover] (MHH), University College of London [London] (UCL), Oslo University College (OUC), Great Ormond Street Hospital for Children [London] (GOSH), Università degli Studi di Padova = University of Padua (Unipd), Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Odense University Hospital (OUH), Environnement périnatal et croissance - EA 4489 (EPS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), University of Nottingham, UK (UON), University of Copenhagen = Københavns Universitet (UCPH), Erasmus University Medical Center [Rotterdam] (Erasmus MC), and Pediatric Surgery
Subjects: medicine.medical_specialty, consensus conference, COLONIC INTERPOSITION, [SDV]Life Sciences [q-bio], MEDLINE, Aftercare, CHILDREN, Anastomosis, Pediatrics, Pyloroplasty, TRACHEOESOPHAGEAL FISTULA, Perioperative Care, PEDIATRIC-SURGERY, 03 medical and health sciences, 0302 clinical medicine, 030225 pediatrics, Pediatric surgery, medicine, follow-up, pediatric surgery, Humans, Esophageal Atresia, EUROPEAN REFERENCE NETWORKS, REPAIR, COMPLICATIONS, OUTCOMES, Science & Technology, business.industry, General surgery, Infant, Newborn, Consensus conference, Perioperative, Long gap esophageal atresia, medicine.disease, 3. Good health, REPLACEMENT, Treatment Outcome, Esophagoplasty, Atresia, Settore MED/20, Pediatrics, Perinatology and Child Health, long-gap esophageal atresia, 030211 gastroenterology & hepatology, Surgery, management, business, Life Sciences & Biomedicine
Abstract: Introduction Evidence supporting best practice for long-gap esophageal atresia is limited. The European Reference Network for Rare Inherited Congenital Anomalies (ERNICA) organized a consensus conference on the management of patients with long-gap esophageal atresia based on expert opinion referring to the latest literature aiming to provide clear and uniform statements in this respect. Materials and Methods Twenty-four ERNICA representatives from nine European countries participated. The conference was prepared by item generation, item prioritization by online survey, formulation of a final list containing items on perioperative, surgical, and long-term management, and literature review. The 2-day conference was held in Berlin in November 2019. Anonymous voting was conducted via an internet-based system using a 1 to 9 scale. Consensus was defined as ≥75% of those voting scoring 6 to 9. Results Ninety-seven items were generated. Complete consensus (100%) was achieved on 56 items (58%), e.g., avoidance of a cervical esophagostomy, promotion of sham feeding, details of delayed anastomosis, thoracoscopic pouch mobilization and placement of traction sutures as novel technique, replacement techniques, and follow-up. Consensus ≥75% was achieved on 90 items (93%), e.g., definition of long gap, routine pyloroplasty in gastric transposition, and avoidance of preoperative bougienage to enable delayed anastomosis. Nineteen items (20%), e.g., methods of gap measurement were discussed controversially (range 1–9). Conclusion This is the first consensus conference on the perioperative, surgical, and long-term management of patients with long-gap esophageal atresia. Substantial statements regarding esophageal reconstruction or replacement and follow-up were formulated which may contribute to improve patient care.
Published: 2020

2. Pratiques autour de l'utilisation des hormones thyroïdiennes chez les patients hypothyroïdiens et euthyroïdiens:un tableau détaillé des résultats du sondage THESIS en France

Author: Camille Buffet, Lisa Belin, Roberto Attanasio, Roberto Negro, Lazlo Hegedüs, Endre V. Nagy, Enrico Papini, Petros Perros, Laurence Leenhardt, Groupe de recherche clinique – Tumeurs Thyroïdiennes [CHU Pitié-Salpêtrière] (GRC-TT), 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), Odense University Hospital (OUH), University of Debrecen, Pontifical University 'Regina Apostolorum', and Royal Victoria Infirmary, Newcastle upon Tyne
Subjects: Male, Pediatrics, Goiter, endocrine system diseases, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Levothyroxine, Hypothyroïdie, Liothyronine, Société Française d’Endocrinologie, 0302 clinical medicine, Endocrinology, Thyroid Hormone Treatment, Surveys and Questionnaires, French Endocrine Society, Medicine, Practice Patterns, Physicians'/statistics & numerical data, Euthyroid, Practice Patterns, Physicians', Survey, sondage, Thyroid, Lévothyroxine, General Medicine, Middle Aged, 16. Peace & justice, 3. Good health, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Euthyroïdie, Drug Therapy, Combination, Female, France, Euthyroidism, medicine.drug, Adult, Infertility, endocrine system, medicine.medical_specialty, 030209 endocrinology & metabolism, 03 medical and health sciences, Hypothyroidism, Humans, business.industry, Hypothyroidism/drug therapy, medicine.disease, Thyroxine, Hormone therapy, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Thyroxine/administration & dosage
Abstract: International audience; Aim: To describe practices of French physicians regarding thyroid hormone therapy, focusing on available LT4 formulations.Material and methods: Members of the French Endocrine Society (FES) and affiliated societies (the Endocrine Tumor Group, French College of Teachers of Endocrinology, Diabetes and Metabolic Diseases and the Union of Endocrinology, Diabetology, Metabolic Diseases and Nutrition Specialists) were invited to participate in an online survey.Results: 534 of the 2,094 persons contacted (25.5%) completed the survey and were included in the analysis. The vast majority (99.4%) reported that levothyroxine (LT4) is the treatment of choice for hypothyroidism. 7.1% and 14.2% of respondents respectively considered liothyronine (LT3) or a combination of LT4 and LT3 for the treatment of hypothyroidism, mainly when symptoms persisted despite achieving normal TSH concentrations with LT4 therapy. For 44% of respondents, thyroid hormone treatment is never indicated in euthyroid patients, while the remainder would consider treating euthyroid patients with a goiter growing over time (40.2%) and/or euthyroid women with positive anti-TPO antibodies and infertility (31.7%). LT4 tablets were the preferred LT4 formulation. A significant proportion of FES members expected no major clinical differences upon changing to formulations such as soft-gel capsules or liquid solutions, even in specific scenarios such as poor biochemical control or suspicion of malabsorption.Conclusion: The treatment of choice for hypothyroidism in France is LT4. LT3-based therapy is considered by some physicians in case of persistent symptoms of hypothyroidism despite normal TSH level. A significant proportion of respondents (66.0%) would consider treating euthyroid patients, contrary to the present state of knowledge. These outdated practices should be addressed by professional bodies such as the FES.; Objectifs: Décrire les pratiques des médecins français concernant l’utilisation thérapeutique des hormones thyroïdiennes, et notamment des formes galéniques disponibles pour la lévothyroxine (LT4).Matériel et méthodes: Les membres de la Société Française d’Endocrinologie (SFE) et de ses sociétés affiliées (le Groupe d’Etudes des Tumeurs Endocrines, le Collège des Enseignants en Endocrinologie, Diabétologie et Maladies Métaboliques et le Syndicat des médecins spécialistes en Endocrinologie, Diabétologie, Maladies Métaboliques et Nutrition) ont été invités à participer à un sondage en ligne.Résultats: Parmi les 2094 personnes contactées, 534 (25,5%) ont répondu et ont été inclus dans l’étude. Selon une très grande majorité d’entre eux (99,4%) la lévothyroxine (LT4) serait le traitement de choix pour l’hypothyroïdie. Respectivement 7,1% et 14,2% envisageraient d’utiliser la liothyronine (LT3) ou l’association de LT4 et LT3 pour l’hypothyroïdie, surtout en cas de symptômes persistants malgré un taux normal de TSH après traitement par LT4. Pour 44% des sondés, les traitements par hormones thyroïdiennes ne sont jamais indiqués pour les patients euthyroïdiens, alors que les autres pourraient éventuellement traiter un patient euthyroïdien avec goitre progressif (40,2%) et / ou une patiente euthyroïdienne infertile et positive pour le anticorps anti-TPO (31,7%). La forme galénique préférée pour la LT4 était sous forme de cachets. Un pourcentage important des membres de la SFE n’anticipait aucune différence clinique majeur si cette forme est remplacée, par exemple, par des capsules de gel mou ou par une solution liquide, même dans des cas spécifiques comme d’absence de contrôle biologique ou de soupçon de malabsorption.Conclusion: Le traitement de choix pour l’hypothyroïdie en France est la LT4. Certains confrères utilisent la LT3 en cas de symptômes persistants d’hypothyroïdie malgré un taux de TSH normal. Selon un pourcentage important des sondés (66.0%), il serait envisageable de mettre en place des traitements pour les patients euthyroïdiens, ce qui ne correspond pas à l’état actuel des connaissances. Les instances professionnelles comme la SFE devraient s’adresser à ces pratiques désuètes.
Published: 2022

3. A polygenic risk score for multiple myeloma risk prediction

Author: Angelica Macauda, Matteo Pelosini, Krzysztof Jamroziak, Mario Petrini, Annette Juul Vangsted, Chiara Piredda, Stephane Minvielle, Marek Dudziński, Hervé Avet-Loiseau, Aleksandra Butrym, Ulla Vogel, Niels Abildgaard, Fabienne Lesueur, Waldemar Tomczak, Vibeke Andersen, Herlander Marques, Daniele Campa, Judit Várkonyi, Rui Manuel Reis, Katalin Kadar, Gabriele Buda, Małgorzata Raźny, Charles Dumontet, Juan Sainz, Anna Suska, Enrico Orciuolo, Agnieszka Druzd-Sitek, Marcin Kruszewski, Daria Zawirska, Niels Frost Andersen, Artur Jurczyszyn, Grzegorz Mazur, Marcin Rymko, Federica Gemignani, Edyta Subocz, Federico Canzian, Katia Beider, Jan Maciej Zaucha, Marzena Wątek, Arnon Nagler, Genomic Epidemiology Group [Heidelberg, Germany] (GEP / DKFZ), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), University of Pisa - Università di Pisa, University Hospital of Cracow/Szpital Uniwersytecki w Krakowie [Poland] (SUK), Aarhus University Hospital, Chaim Sheba Medical Center, Sea Hospital [Gdynia, Poland] (SH), Wroclaw Medical University [Wrocław, Pologne] (WMU), Hospices Civils de Lyon (HCL), Holycross Cancer Center of Kelce, Hematology Clinic, Kielce, Institute of Hematology and Transfusion Medicine [Warsaw, Poland] (IHTM), Centre for Genomics and Oncological Research Pfizer [Granada, Spain] (GENYO), University of Granada [Granada]-Andalusian Regional Government [Granada, Spain], Hospital Universitario Virgen de las Nieves [Granada, Spain] (HUVN), Semmelweis University [Budapest], Odense University Hospital (OUH), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Teaching Hospital No 1 [Rzeszów, Poland] (TH1), University of Copenhagen = Københavns Universitet (KU), Military Institute of Medicine [Warsaw, Poland] (MIM), Rydygier Specialistic Hospital [Cracow, Poland] (RSH), University of Minho [Braga], Jagiellonian University Medical College [Cracow, Poland] (JUMC), Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), The National Research Center for Work Environment [Copenhagen, Denmark] (NRCWE), University of Southern Denmark (SDU), ICVS/3B's - PT Government Associate Laboratory [Braga/Guimarães, Portugal] (AL), Barretos Cancer Hospital [São Paulo, Brazil] (BCH), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), University Hospital Bydgoszcz [Bydgoszcz, Poland] (UHB), Medical University of Lublin, N. Copernicus Town Hospital [Torun, Poland] (NCTH), Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression (CRCINA-ÉQUIPE 11), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Bernardo, Elizabeth, Wrocław Medical University, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universidad de Granada = University of Granada (UGR)-Andalusian Regional Government [Granada, Spain], Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Copenhagen = Københavns Universitet (UCPH), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: Oncology, medicine.medical_specialty, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Single-nucleotide polymorphism, Genome-wide association study, Polymorphism, Single Nucleotide, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Risk Factors, Internal medicine, Genetics, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, education, Genetics (clinical), Multiple myeloma, 030304 developmental biology, Genetic association, 0303 health sciences, education.field_of_study, business.industry, medicine.disease, Penetrance, 3. Good health, 030220 oncology & carcinogenesis, Polygenic risk score, Multiple Myeloma, business, Genome-Wide Association Study
Abstract: This work was partially supported by intramural funds of the University of Pisa, DKFZ, and University Hospital of Southern Jutland, Denmark, and by a grant of the French National Cancer Institute (INCA). The authors wish to thank Dr. Dominic Edelmann (Division of Biostatistics, DKFZ) for helpful advice about data analysis., There is overwhelming epidemiologic evidence that the risk of multiple myeloma (MM) has a solid genetic background. Genome-wide association studies (GWAS) have identified 23 risk loci that contribute to the genetic susceptibility of MM, but have low individual penetrance. Combining the SNPs in a polygenic risk score (PRS) is a possible approach to improve their usefulness. Using 2361 MM cases and 1415 controls from the International Multiple Myeloma rESEarch (IMMEnSE) consortium, we computed a weighted and an unweighted PRS. We observed associations with MM risk with OR = 3.44, 95% CI 2.53-4.69, p = 3.55 x 10(-15) for the highest vs. lowest quintile of the weighted score, and OR = 3.18, 95% CI 2.1 = 34-4.33, p = 1.62 x 10(-13) for the highest vs. lowest quintile of the unweighted score. We found a convincing association of a PRS generated with 23 SNPs and risk of MM. Our work provides additional validation of previously discovered MM risk variants and of their combination into a PRS, which is a first step towards the use of genetics for risk stratification in the general population., University of Pisa, DKFZ, University Hospital of Southern Jutland, Denmark, Institut National du Cancer (INCA) France
Published: 2021

4. Integrative approach to interpret DYRK1A variants, leading to a frequent neurodevelopmental disorder

Author: Marjolaine Willems, Benjamin Durand, Boris Keren, Kristina Pilekær Sørensen, Rosanna Weksberg, Magalie Barth, Christina Fagerberg, Cyril Mignot, Laurence Perrin, Lucas Bronicki, Nathalie Drouot, Imene Boujelbene, Marc Abramowicz, Maria Kibaek, Bertrand Isidor, Thierry Bienvenu, Mathilde Nizon, Perrine Charles, Laurent Pasquier, Yann Herault, Marie Christine Birling, Bruno Delobel, Michel Guipponi, Lydie Burglen, Mélanie Fradin, Anne Sophie Denommé, Florence Demurger, Benjamin Cogné, Sébastien Moutton, Allan Bayat, Frederic Tran Mau Them, Christèle Dubourg, Alice Goldenberg, Christine Francannet, Jean-Louis Mandel, Laurence Faivre, Jérémie Courraud, Anne Marie Guerrot, Julia Metreau, Loréline Genschik, Bénédicte Demeer, Marie Vincent, Mathilde Renaud, Julien Thevenon, Sandrine Passemard, Christine Coubes, Amélie Piton, David Geneviève, Maria del Mar Muniz Moreno, Bénédicte Gérard, Estelle Colin, Valérie Layet, Michèle Mathieu-Dramard, Salima El Chehadeh, Katrine M Johannesen, Julie D. Thompson, Cathrine Elisabeth Tronhjem, Pascale Saugier, Elise Schaefer, Eric Chater-Diehl, Séverine Drunat, Rikke S. Møller, Paul Kuentz, Claire Feger, Albert David, Antonio Vitobello, Marlène Rio, Khaoula Khachnaoui, Joane Svane, Stéphane Auvin, 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), The Hospital for sick children [Toronto] (SickKids), Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Les Hôpitaux Universitaires de Strasbourg (HUS), Hôpital Universitaire de Genève, Children's hospital of Eastern Ontario Research Institute [Ottawa, canada] (CHEO), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Hôpital Saint Vincent de Paul de Lille, Groupe Hospitalier de l'Institut Catholique de Lille (GHICL), Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Hôpital Robert Debré, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Hôpital Sud [CHU Rennes], CHU Pontchaillou [Rennes], CHU Clermont-Ferrand, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU), The Danish Epilepsy Centre Filadelfia [Dianalund, Denmark], University of Southern Denmark (SDU), Odense University Hospital (OUH), CHU Amiens-Picardie, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Odense University Hospital [Odense, Denmark], Centre Hospitalier Universitaire [Grenoble] (CHU), Groupe Hospitalier du Havre, Maladies neurodéveloppementales et neurovasculaires (NeuroDiderot (UMR_S_1141 / U1141)), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nice (CHU Nice), Institut Clinique de la Souris, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Hôpital Cochin [AP-HP], Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), University of Toronto, Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Sorbonne Université, Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), Centre for Integrative Biology - CBI (Inserm U964 - CNRS UMR7104 - IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Laboratoire de Génétique Médicale (LGM), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Agence de Biomédecine, Fondation APLM, Fondation Maladies Rares and Fondation Jérome Lejeune, univOAK, Archive ouverte, Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), and Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [INFO.INFO-AI] Computer Science [cs]/Artificial Intelligence [cs.AI], DYRK1A, [SDV]Life Sciences [q-bio], [SDV.GEN] Life Sciences [q-bio]/Genetics, Protein Serine-Threonine Kinases, Biology, [INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI], Mice, 03 medical and health sciences, 0302 clinical medicine, Neurodevelopmental disorder, Intellectual Disability, medicine, Animals, Humans, Missense mutation, Kinase activity, Gene, Genetics (clinical), Cellular localization, 030304 developmental biology, Genetics, [SDV.GEN]Life Sciences [q-bio]/Genetics, 0303 health sciences, Protein-Tyrosine Kinases, medicine.disease, Phenotype, Human genetics, 3. Good health, 030220 oncology & carcinogenesis, Microcephaly
Abstract: Purpose: DYRK1A syndrome is among the most frequent monogenic forms of intellectual disability (ID). We refined the molecular and clinical description of this disorder and developed tools to improve interpretation of missense variants, which remains a major challenge in human genetics. Methods: We reported clinical and molecular data for 50 individuals with ID harboring DYRK1A variants and developed (1) a specific DYRK1A clinical score; (2) amino acid conservation data generated from 100 DYRK1A sequences across different taxa; (3) in vitro overexpression assays to study level, cellular localization, and kinase activity of DYRK1A mutant proteins; and (4) a specific blood DNA methylation signature. Results: This integrative approach was successful to reclassify several variants as pathogenic. However, we questioned the involvement of some others, such as p.Thr588Asn, still reported as likely pathogenic, and showed it does not cause an obvious phenotype in mice. Conclusion: Our study demonstrated the need for caution when interpreting variants in DYRK1A, even those occurring de novo. The tools developed will be useful to interpret accurately the variants identified in the future in this gene. Graphic abstract: [Figure not available: see fulltext.]
Published: 2021

5. Management of anaphylaxis due to COVID-19 vaccines in the elderly

Author: Paulo Augusto Moreira Camargos, Radolslaw Gawlik, Mirko Petrovic, Gunter J. Sturm, Kristof Nekam, Sergio Bonini, Zhanat Ispayeva, Marilyn Urrutia Pereira, Jean Bousquet, Antti Lauerma, Menachem Rottem, Arzu Yorgancioglu, Hubert Blain, Antonio Cherubini, Mário Morais-Almeida, Nathalie Salles, Charlotte G. Mortz, Sylwia Smolinska, Davor Plavec, A. Bedbrook, Torsten Zuberbier, Helga Kraxner, M. Beatrice Bilò, Sinthia Bosnic-Anticevich, Gaëtan Gavazzi, Finbarr C. Martin, Alvaro A. Cruz, K. S. Bennoor, Isabella Annesi-Maesano, Mohamed H. Shamji, Karin Hoffmann-Sommergruber, Marina Atanaskovic-Markovic, Carsten Bindslev-Jensen, Lan Tt Le, Isabel Skypala, Ana Todo-Bom, Vincenzo Patella, Lorenzo Cecchi, Charlotte Suppli Ulrik, Oscar Palomares, Joaquin Sastre, Hans Jürgen Hoffmann, Knut Brockow, Eva Untersmayr, Martin Hrubisko, Bernadette Eberlein, Aziz Sheikh, Milan Sova, Osman M. Yusuf, Violeta Kvedariene, G. Walter Canonica, Dana Wallace, Ioana Agache, Milena Sokolowska, Jos M. G. A. Schols, Susan Waserman, Stéphanie Miot, Carla Irani, Regina E Roller-Winsberger, Michael Levin, Yves Rolland, Emma Montella, Bilun Gemicioglu, Bolesław Samoliński, Stefano Del Giacco, Madda lenaIllario, Yehia El-Gamal, Olga Lourenço, Jean-Christoph Roger J-P Caubet, Luisa Brussino, Marysia Recto, De Yun Wang, Igor Kaidashev, Renaud Louis, Antonino Romano, Mario E. Zernotti, Jacques Reynes, Pedro Carreiro-Martins, Alexandra F. Santos, Marek Niedoszytko, M. Gotua, Musa Khaitov, Thomas B. Casale, Andrea Matucci, Bernardo Sousa-Pinto, Rafael Stelmach, Dejan Dokic, Joana Vitte, Motohiro Ebisawa, Maria Teresa Ventura, Joaquim Mullol, Tomas Chivato, Petr Panzner, Oliver Pfaar, Sanna Toppila-Salmi, Ioanna Tsiligianni, Wytske Fokkens, Alessandra Vultaggio, H. Neffen, Juan Carlos Ivancevich, Ya-dong Gao, Anna Sediva, Maja Hofmann, Ana Maria Carriazo, João Fonseca, Marek Jutel, A. Benetos, Nhân Pham-Thi, Mona Al-Ahmad, Arunas Valiulis, Mihaela Zidarn, Elizabeth Angier, Yoshitaka Okamoto, Montserrat Fernandez-Rivas, Cezmi A. Akdis, Philip W. Rouadi, Olivier Guérin, John Farrell, Mikaela Odemyr, George Christoff, Vera Mahler, Claus Bachert, Edward F. Knol, Wienczyslawa Czarlewski, Robyn E O'Hehir, Victoria Cardona, Ludger Klimek, Tari Haahtela, Vincent Le Moing, Branislava Milenkovic, Carmen Rondon, Kaja Julge, Jolanta Walusiak-Skorupa, Nikolaos G. Papadopoulos, Aslı Gelincik, Markus Ollert, Piotr Kuna, Leyla Namazova-Baranova, Margitta Worm, Annick Barbaud, Elena Camelia Berghea, Todor A. Popov, Derek K. Chu, María José Torres, Faradiba Sarquis Serpa, Nicola Scichilone, Amir Hamzah Abdul Latiff, Frederico S. Regateiro, Gianni Passalacqua, Humboldt-Universität zu Berlin, Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Center for Rhinology and Allergology Wiesbaden, University Hospital Mannheim, Humboldt University Of Berlin, Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Transylvania University, Wrocław Medical University, Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], University of Cagliari, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Università Politecnica delle Marche [Ancona] (UNIVPM), Medical Consulting Czarlewski, Universiti Putra Malaysia, University of Southampton, Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), University of Belgrade [Belgrade], Ghent University Hospital, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Dhaka Shishu Hospital [Bangladesh], University of Medicine and Pharmacy 'Carol Davila' Bucharest (UMPCD), Odense University Hospital (OUH), Italian National Research Council, National Research Council [Italy] (CNR), The University of Sydney, Technische Universität München = Technical University of Munich (TUM), Università degli studi di Torino = University of Turin (UNITO), Universidade Federal de Minas Gerais = Federal University of Minas Gerais [Belo Horizonte, Brazil] (UFMG), IRCCS Research Hospital, Milan, Vall d'Hebron University Hospital [Barcelona], Centro Hospitalar de Lisboa Central E.P.E, University of South Florida [Tampa] (USF), Geneva University Hospital (HUG), Azienda Usl Toscana centro [Firenze], Софийски университет = Sofia University, McMaster University [Hamilton, Ontario], State University of Bahia, Institute of Public Health of Republic of North Macedonia [Skopje], Ain Shams University (ASU), Sagamihara National Hospital [Kanagawa, Japan], Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), Amsterdam UMC - Amsterdam University Medical Center, Universidade do Porto = University of Porto, Wuhan University [China], CHU Grenoble, Silesian University of Medicine, Istanbul Faculty of Medicine, Cerrahpasa Faculty of Medicine, Istanbul University, Centre Hospitalier Universitaire de Nice (CHU Nice), Helsinki University Hospital [Helsinki, Finlande], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Medizinische Universität Wien = Medical University of Vienna, Aarhus University [Aarhus], Oncology Institute of St Elisabeth, University of Naples Federico II = Università degli studi di Napoli Federico II, St Joseph University, Hôtel-Dieu de France (HDF), Université Saint-Joseph de Beyrouth (USJ), Kazakh National Medical University, Servicio de Alergia e ImmunologiaBuenos Aires (Clinica Santa Isabel), Tartu University Institute of Clinical Medicine, Ukrainina Medical Stomatological Academy [Poltava, Ukraine], Federal Medicobiological Agency [Moscow, Russian Federation], University Medical Center [Utrecht], Semmelweis University [Budapest], Medical University of Łódź (MUL), Vilnius University [Vilnius], University of Medicine and Pharmacy (VIETNAM), University of Cape Town, CHU Sart Tilman, Université de Liège, University of Beira Interior [Portugal] (UBI), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), uBibliorum, Ear, Nose and Throat, AII - Inflammatory diseases, CHU Montpellier, Wroclaw Medical University [Wrocław, Pologne], University of Bari Aldo Moro (UNIBA), Service de Médecine Interne = Hôpital de jour de médecine [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sagamihara National Hospital, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Toulouse [Toulouse], RS: CAPHRI - R1 - Ageing and Long-Term Care, Health Services Research, Bousquet J., Agache I., Blain H., Jutel M., Ventura M.T., Worm M., Del Giacco S., Benetos A., Bilo B.M., Czarlewski W., Abdul Latiff A.H., Al-Ahmad M., Angier E., Annesi-Maesano I., Atanaskovic-Markovic M., Bachert C., Barbaud A., Bedbrook A., Bennoor K.S., Berghea E.C., Bindslev-Jensen C., Bonini S., Bosnic-Anticevich S., Brockow K., Brussino L., Camargos P., Canonica G.W., Cardona V., Carreiro-Martins P., Carriazo A., Casale T., Caubet J.-C., Cecchi L., Cherubini A., Christoff G., Chu D.K., Cruz A.A., Dokic D., El-Gamal Y., Ebisawa M., Eberlein B., Farrell J., Fernandez-Rivas M., Fokkens W.J., Fonseca J.A., Gao Y., Gavazzi G., Gawlik R., Gelincik A., Gemicioglu B., Gotua M., Guerin O., Haahtela T., Hoffmann-Sommergruber K., Hoffmann H.J., Hofmann M., Hrubisko M., Illario M., Irani C., Ispayeva Z., Ivancevich J.C., Julge K., Kaidashev I., Khaitov M., Knol E., Kraxner H., Kuna P., Kvedariene V., Lauerma A., Le L.T.T., Le Moing V., Levin M., Louis R., Lourenco O., Mahler V., Martin F.C., Matucci A., Milenkovic B., Miot S., Montella E., Morais-Almeida M., Mortz C.G., Mullol J., Namazova-Baranova L., Neffen H., Nekam K., Niedoszytko M., Odemyr M., O'Hehir R.E., Okamoto Y., Ollert M., Palomares O., Papadopoulos N.G., Panzner P., Passalacqua G., Patella V., Petrovic M., Pfaar O., Pham-Thi N., Plavec D., Popov T.A., Recto M.T., Regateiro F.S., Reynes J., Roller-Winsberger R.E., Rolland Y., Romano A., Rondon C., Rottem M., Rouadi P.W., Salles N., Samolinski B., Santos A.F., S Sarquis F., Sastre J., M. G. A. Schols J., Scichilone N., Sediva A., Shamji M.H., Sheikh A., Skypala I., Smolinska S., Sokolowska M., Sousa-Pinto B., Sova M., Stelmach R., Sturm G., Suppli Ulrik C., Todo-Bom A.M., Toppila-Salmi S., Tsiligianni I., Torres M., Untersmayr E., Urrutia Pereira M., Valiulis A., Vitte J., Vultaggio A., Wallace D., Walusiak-Skorupa J., Wang D.-Y., Waserman S., Yorgancioglu A., Yusuf O.M., Zernotti M., Zidarn M., Chivato T., Akdis C.A., Zuberbier T., Klimek L., HUS Inflammation Center, University of Helsinki, and Department of Dermatology, Allergology and Venereology
Subjects: Male, Allergy, Pediatrics, Eaaci Position Paper, COVID-19 vaccines, older (adults, GUIDELINES, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine and Health Sciences, Immunology and Allergy, Medicine, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Geriatrics, MESH: Aged, RISK, Vaccines, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, people), EPINEPHRINE, Epinephrine, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, COVID -19 vaccines, Anaphylaxis, medicine.drug, older (adults/people), medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), MESH: Covid-19, MESH: Epinephrine, Immunology, adrenaline, anaphylaxis, Aged, COVID-19 Vaccines, Humans, SARS-CoV-2, COVID-19, Settore MED/10 - Malattie Dell'Apparato Respiratorio, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Diabetes mellitus, Anaphylaxis/etiology, MESH: SARS-CoV-2, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, COVID‐19 vaccines, Older - Adults/people, Asthma, MESH: Humans, business.industry, adrenaline, anaphylaxis, COVID-19 vaccines, older (adults/people), medicine.disease, Obesity, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Male, MESH: Anaphylaxis, Older, 3121 General medicine, internal medicine and other clinical medicine, business, MESH: Covid-19 vaccines, 030215 immunology
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Published: 2021

6. Association of sensory phenotype with quality of life, functionality, and emotional well-being in patients suffering from neuropathic pain

Author: Maija Haanpää, Rolf-Detlef Treede, Rainer Freynhagen, Juliane Sachau, Søren H. Sindrup, Troels S. Jensen, Christoph Maier, Jan Vollert, Janne Gierthmühlen, Jeffrey D. Kennedy, Nadine Attal, Thomas R. Tölle, Didier Bouhassira, Märta Segerdahl, Andrew S.C. Rice, Johann Böhmer, Lise Ventzel, Ralf Baron, Per Hansson, University Medical Center of Schleswig–Holstein = Universitätsklinikum Schleswig-Holstein (UKSH), Kiel University, Physiopathologie et Pharmacologie Clinique de la Douleur (LPPD), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Benedictus Hospital Feldafing, Technische Universität München = Technical University of Munich (TUM), Helsinki University Hospital [Finland] (HUS), Oslo University Hospital [Oslo], Karolinska Institutet [Stockholm], Aarhus University Hospital, Eli Lilly and Company [Indianapolis], Ruhr University Bochum (RUB), Imperial College London, Odense University Hospital (OUH), Heidelberg University, This project has received funding from an Innovative Medicines Initiative 1 EUROPAIN under grant No [115007] and from an Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No [777500]. This joint undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. (www.imi.europe.eu, European Project: 115007,EC:FP7:SP1-JTI,IMI-JU-01-2008,EUROPAIN(2009), HAL UVSQ, Équipe, and Understanding chronic pain and improving its treatment - EUROPAIN - - EC:FP7:SP1-JTI2009-10-01 - 2015-09-30 - 115007 - VALID
Subjects: PRO, Quality of life, medicine.medical_specialty, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Sensory system, Sensory phenotype, Neuropathic pain, Emotional well-being, Physical medicine and rehabilitation, medicine, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Brief Pain Inventory, Functionality, business.industry, Chronic pain, Sensory loss, medicine.disease, QST, Anesthesiology and Pain Medicine, Phenotype, Neurology, Hyperalgesia, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Anxiety, Neuralgia, Pain catastrophizing, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology (clinical), medicine.symptom, Chronic Pain, business
Abstract: International audience; Neuropathic pain highly affects quality of life, well-being, and function. It has recently been shown based on cluster analysis studies that most patients with neuropathic pain may be categorized into 1 of 3 sensory phenotypes: sensory loss, mechanical hyperalgesia, and thermal hyperalgesia. If these phenotypes reflect underlying pathophysiological mechanisms, they may be more relevant for patient management than underlying neurological diagnosis or pain intensity. The aim of this study was thus to examine the impact of these sensory phenotypes on mental health, functionality, and quality of life. Data of 433 patients from the IMI/EuroPain network database were analyzed, and results of HADS-D/A, Pain Catastrophizing Scale, Euro Quality of Life 5D/-VAS, Brief Pain Inventory, and Graded Chronic Pain Scale between the sensory phenotypes were compared using multiple regression analysis. There was no difference in chronic pain grade, pain intensity, depression, or anxiety scores between phenotypes. Pain interference (Brief Pain Inventory) was higher (P = 0.002); self-reported health state lower (Euro Quality of Life 5D VAS, P = 0.02); and problems regarding mobility (P = 0.008), usual activities (P = 0.004), and self-care (P = 0.039) more prominent (EQ5-D) in the sensory loss compared with the thermal hyperalgesia phenotype. Patients with sensory loss also showed higher pain catastrophizing scores (P = 0.006 and 0.022, respectively) compared with the 2 other groups. Sensory phenotype is associated with the impact of neuropathic pain conditions on well-being, daily functionality, and quality of life but is less associated with pain intensity. These results suggest that the somatosensory phenotype should be considered for personalized pain management. Copyright
Published: 2022

7. Breast milk n-3 long-chain polyunsaturated fatty acids and blood pressure

Author: Barbara Heude, Alet H. Wijga, Ken D. Stark, Hans Bisgaard, Signe Bruun, Rebecca K. Vinding, Kim F. Michaelsen, Klaus Bønnelykke, Henriette Boye Kyhl, Henriette A. Smit, Carel Thijs, Steffen Husby, Lenie van Rossem, Martine Armand, Jonathan Y. Bernard, Lotte Lauritzen, Utrecht University [Utrecht], Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), 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), University of Copenhagen = Københavns Universitet (UCPH), Odense University Hospital (OUH), Epidémiologie cardiovasculaire et métabolique, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Waterloo [Waterloo], Maastricht University [Maastricht], National Institute for Public Health and the Environment [Bilthoven] (RIVM), Netherlands Heart Foundation (Grant no. 2013T025), 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), University of Copenhagen = Københavns Universitet (KU), Odense University Hospital, Department of Epidemiology, Maastricht University [Maastricht]-School for Public Health and Primary Care (CAPHRI), Epidemiologie, RS: CAPHRI - R5 - Optimising Patient Care, Obstetrics & Gynecology, and Armand, Martine
Subjects: Male, LACTATION, Docosahexaenoic Acids, Breastfeeding, CHILDHOOD, Medicine (miscellaneous), Physiology, HEART-RATE, 030204 cardiovascular system & hematology, Breast milk, FISH-OIL SUPPLEMENTATION, 03 medical and health sciences, 0302 clinical medicine, LATER LIFE, Lactation, Fatty Acids, Omega-3, Faculty of Science, medicine, Humans, 030212 general & internal medicine, Fatty acids, Children, chemistry.chemical_classification, Nutrition and Dietetics, Milk, Human, business.industry, food and beverages, Original Contribution, ARACHIDONIC-ACID, DOCOSAHEXAENOIC ACID, PREVENTION, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Breast Feeding, Blood pressure, medicine.anatomical_structure, PREGNANCY, chemistry, Docosahexaenoic acid, Meta-analysis, Cohort, Fatty Acids, Unsaturated, INFANCY, Female, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Polyunsaturated fatty acid
Abstract: Purpose It is controversial whether a higher intake of n-3 long-chain polyunsaturated fatty acids (n-3 LC PUFA) through breastfeeding is associated or not to a lower blood pressure (BP) during childhood. We aimed to clarify this point by undertaking a meta-analysis involving the data from seven European birth cohorts. Methods We searched https://www.birthcohort.net for studies that had collected breast milk samples, and had at least one BP measurement in childhood. Principal investigators were contacted, and all agreed to share data. One additional study was identified by contacts with the principal investigators. For each cohort, we analyzed the association of breast milk n-3 LC PUFAs with systolic and diastolic BP with linear mixed effects models or linear regression, and pooled the estimates with a random effects model. We also investigated age-specific and sex-specific associations. Results A total of 2188 participants from 7 cohorts were included. Overall, no associations between breast milk n-3 LC PUFAs and BP were observed. In the pooled analysis, each 0.1 wt% increment in breast milk docosahexaenoic acid (DHA) was associated with a 1.19 (95% CI − 3.31, 0.94) mmHg lower systolic BP. Associations were similar for boys and girls and at different ages. Conclusion In this individual participant meta-analysis, we found no evidence for an association between breast milk n-3 LC PUFAs and BP.
Published: 2021

8. COVID-19 pandemic

Author: W. J. Fokkens, Jürgen Schwarze, Cezmi A. Akdis, J Mullol, W. Czarlewski, Claudia Traidl-Hoffmann, Claus Bachert, D. Larenas-Linnemann, Tomas Chivato, M. Gotua, Mateo Bonini, Ludger Klimek, Vincenzo Patella, A. A. Cruz, Stephanie Dramburg, Kari C. Nadeau, H W Fritsch, K. Ohta, Thomas Eiwegger, Robert M. Naclerio, Antti Lauerma, A. Yorgancioglu, Aslı Gelincik, Piotr Kuna, Oliver Pfaar, Carmen Riggioni, Violeta Kvedariene, Markus Ollert, Sinthia Bosnic-Anticevich, V. Cardona, S. Del Giacco, Sanna Toppila-Salmi, Helen A. Brough, Heimo Breiteneder, Valérie Hox, B. Samolinski, Zuzana Diamant, G.W. Canonica, Lihong Zhang, María José Torres, Y. Okamoto, Liam O'Mahony, Radosław Gawlik, Jolanta Walusiak-Skorupa, Sharon Chinthrajah, Winfried Rief, T. Haatela, M. Morais-Almeida, Ioana Agache, Manfred Schedlowski, I Skypala, R. Brehler, D. Y. Wang, João Fonseca, I. J. Ansotegui, Robyn E O'Hehir, Oscar Palomares, Charlotte G. Mortz, J. C. Ivancevich, C. Suppli Ulrik, M. T. Ventura, P M Matricardi, S Untersmayr, Gabrielle L. Onorato, Amir Hamzah Abdul Latiff, Frederico S. Regateiro, Vanitha Sampath, Arũnas Valiulis, Marek Jutel, Luisa Brussino, Pedro Carreiro-Martins, Jean Bousquet, Nikolaos G. Papadopoulos, A. Bedbrook, Torsten Zuberbier, Karin Hoffmann-Sommergruber, Edward F. Knol, Ear, Nose and Throat, AII - Inflammatory diseases, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, UCL - (SLuc) Service d'oto-rhino-laryngologie, Philipps Universität Marburg = Philipps University of Marburg, Allergologie, Stimm und Sprachstörungen [Wiesbaden, Germany], Zentrum für Rhinologie und Allergologie [Wiesbaden, Germany], University of Wrocław [Poland] (UWr), ALL-MED, Swiss Institute of Allergy and Asthma Research (SIAF), Universität Zürich [Zürich] = University of Zurich (UZH), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Medizinische Universität Wien = Medical University of Vienna, Stanford University, Skane University Hospital [Malmo], Lund University [Lund], Charles University [Prague] (CU), University Medical Center Groningen [Groningen] (UMCG), Univ Toronto, Hosp Sick Children, Peter Gilgan Ctr Res & Learning, Mol Med, Toronto, ON M5G 0A4, Canada, The Hospital for sick children [Toronto] (SickKids), University of Toronto, Amsterdam UMC - Amsterdam University Medical Center, Alfred Health, Victoria University [Melbourne], University College Cork (UCC), Sean N. Parker Center for Allergy and Asthma Research [Stanford], Stanford Medicine, Stanford University-Stanford University, University Clinics of Essen, University of Essen, Allergy Unit [Malaga, Spain] (National Network ARADyAL), Hospital Regional Universitario de Málaga = Regional University Hospital of Malaga [Spain], Helmholtz Zentrum München = German Research Center for Environmental Health, University Hospital Augsburg, National University of Singapore (NUS), Beijing Tongren Hospital, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, University Hospital Münster - Universitaetsklinikum Muenster [Germany] (UKM), Evelina London Children's Hospital, King‘s College London, CEU-San Pablo University and HM-Hospitals School of Medicine, University of Cagliari, Medical University of Silesia (SUM), Istanbul University, Cliniques Universitaires Saint-Luc [Bruxelles], University Medical Center [Utrecht], Helsinki University Central Hospital, University of Helsinki, Odense University Hospital (OUH), Luxembourg Institute of Health (LIH), Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Hospital Sant Joan de Déu [Barcelona], Institut de Recerca Pediàtrica Hospital Sant Joan de Déu [Barcelona, Spain], University of Edinburgh, NHS Foundation Trust [London], The Royal Marsden, Nofer Institute of Occupational Medicine (NIOM), Hospital Quirónsalud Bizkaia [Bilbao], Ghent University Hospital, Sun Yat-Sen University [Guangzhou] (SYSU), Karolinska Institutet [Stockholm], Woolcock Institute of Medical Research [Sydney], The University of Sydney, University of Turin, Mauriziano Umberto I Hospital, Humanitas University [Milan] (Hunimed), Vall d'Hebron University Hospital [Barcelona], Hospital de Dona Estefania, NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Federal University of Bahia School of Medicine, Global Alliance Against Chronic Respiratory Diseases (GARD-WHO), Medical Consulting Czarlewski, Faculdade de Medicina da Universidade do Porto (FMUP), Universidade do Porto = University of Porto, MEDIDA, Lda, David Tvildiani Medical University (DTMU), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Servicio de Alergia e ImmunologiaBuenos Aires (Clinica Santa Isabel), Barlicki University Hospital, Vilnius University [Vilnius], Hospital Medica Sur [Mexico City, Mexico], Pantai Hospital [Kuala Lumpur], Hospital CUF Descobertas, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), CIBER de Epidemiología y Salud Pública (CIBERESP), Johns Hopkins University School of Medicine [Baltimore], Fukujuji Hospital, Tokyo National Hospital, Chiba Rosai Hospital, Chiba University Hospital, Royal Manchester Children's Hospital, University of Manchester [Manchester], General Children's Hospital of Athens P & A Kyriakou, 'Santa Maria della Speranza' Hospital, Centro Hospitalar e Universitário [Coimbra], Coimbra Institute for Clinical and Biomedical Research [Coimbra, Portugal] (iCBR - Faculty of Medicine), University of Coimbra [Portugal] (UC), Medical University of Warsaw - Poland, Hvidovre Hospital, University of Copenhagen = Københavns Universitet (UCPH), Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Manisa Celal Bayar University, Transilvania University of Brasov, Salvy-Córdoba, Nathalie, Department of Dermatology, Allergology and Venereology, and HUS Inflammation Center
Subjects: 0301 basic medicine, viruses, Eaaci Position Paper, Medizin, Cochrane Library, GUIDELINES, FOOD ALLERGY, allergen immunotherapy, allergy clinic, anaphylaxis, asthma, clinical trials, COVID-19, Position Paper, psychological impact, SARS-CoV-2, Allergists, Health Personnel, Humans, Hypersensitivity, Information Technology, Patient Care Team, Triage, SARS‐CoV‐2, DESENSITIZATION, 0302 clinical medicine, MESH: Patient Care Team, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, HDE ALER, Pandemic, Health care, Immunology and Allergy, ATOPIC-DERMATITIS, MESH: COVID-19, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, [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, allergen immunotherapy (AIT), virus diseases, DRUG HYPERSENSITIVITY REACTIONS, 3. Good health, INFECTIONS, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Triage, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology, Allergen immunotherapy, medicine.medical_specialty, MESH: Information Technology, MESH: Hypersensitivity, Immunology, education, MEDLINE, DIAGNOSIS, psychological COVID, 03 medical and health sciences, MESH: Allergists, COVID‐19, medicine, MESH: SARS-CoV-2, ddc:610, RHINOSINUSITIS, MESH: Humans, business.industry, Clinical trial, Coronavirus, EXACERBATIONS, 030104 developmental biology, 030228 respiratory system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Family medicine, 3121 General medicine, internal medicine and other clinical medicine, Position paper, MESH: Health Personnel, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: BackgroundThe Coronavirus disease 2019 (COVID‐19) has evolved as a pandemic infectious disease transmitted by the severe acute respiratory syndrome coronavirus (SARS‐CoV‐)2. Allergists and other health care providers (HCPs) in the field of allergies and associated airway diseases are in the front line, taking care of patients potentially infected with SARS‐CoV‐2. Hence, strategies and practices to minimize risks of infection for both HCPs and treated patients have to be developed and followed by allergy clinics.MethodThe scientific information on COVID‐19 was analyzed by a literature search in Medline, Pubmed, national and international guidelines from the European Academy of Allergy and Clinical Immunology (EAACI), the Cochrane Library and the Internet.ResultsBased on diagnostic and treatment standards developed by EAACI, on international information regarding COVID‐19, on guidelines of the World Health Organization (WHO) and other international organizations as well as on previous experience, a panel of experts including clinicians, psychologists, IT experts and basic scientists along with EAACI and the “Allergic Rhinitis and its Impact on Asthma (ARIA)” inititiative have developed recommendations for the optimal management of allergy clinics during the current COVID‐19 pandemic. These recommendations are grouped into nine sections on different relevant aspects for the care of patients with allergies.ConclusionsThis international Position Paper provides recommendations on operational plans and procedures to maintain high standards in the daily clinical care of allergic patients whilst ensuring necessary safety in the current COVID‐19 pandemic.
Published: 2021

9. European consensus-based interdisciplinary guideline for melanoma. Part 1: Diagnostics: Update 2022

Author: Garbe, Claus, Amaral, Teresa, Peris, Ketty, Hauschild, Axel, Arenberger, Petr, Basset-Seguin, Nicole, Bastholt, Lars, Bataille, Veronique, Del Marmol, Veronique, Dréno, Brigitte, Fargnoli, Maria C, Forsea, Ana-Maria, Grob, Jean-Jacques, Höller, Christoph, Kaufmann, Roland, Kelleners-Smeets, Nicole, Lallas, Aimilios, Lebbé, Celeste, Lytvynenko, Bohdan, Malvehy, Josep, Moreno-Ramirez, David, Nathan, Paul, Pellacani, Giovanni, Saiag, Philippe, Stratigos, Alexander J, Van Akkooi, Alexander C J, Vieira, Ricardo, Zalaudek, Iris, Lorigan, Paul, European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO), and the European Organization for Research and Treatment of Cancer (EORTC), Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), University Hospital Schleswig-Holstein [Kiel, Germany], Charles University [Prague] (CU), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Odense University Hospital (OUH), King‘s College London, Université libre de Bruxelles (ULB), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), University of L'Aquila [Italy] (UNIVAQ), University of Medicine and Pharmacy 'Carol Davila' Bucharest (UMPCD), Aix Marseille Université (AMU), Medizinische Universität Wien = Medical University of Vienna, Frankfurt University Hospital, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Aristotle University of Thessaloniki, Shupyk National Medical Academy of Postgraduate Education [Kiev] (SNMAPE), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Clinic Barcelona Hospital Universitari, Hospital Universitario Virgen Macarena [Séville], Mount Vernon Cancer Centre [Northwood, UK] (MV2C), Mount Vernon Cancer Centre, University - Hospital of Modena and Reggio Emilia [Modena, Italy], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), University of Athens Medical School [Athens], The University of Sydney, Centro Hospitalar e Universitário [Coimbra], Università degli studi di Trieste = University of Trieste, University of Manchester [Manchester], European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO), and the European Organization for Research and Treatment of Cancer (EORTC), Pecqueret, Valérie, Garbe, Clau, Amaral, Teresa, Peris, Ketty, Hauschild, Axel, Arenberger, Petr, Basset-Seguin, Nicole, Bastholt, Lar, Bataille, Veronique, Del Marmol, Veronique, Dréno, Brigitte, Fargnoli, Maria C, Forsea, Ana-Maria, Grob, Jean-Jacque, Höller, Christoph, Kaufmann, Roland, Kelleners-Smeets, Nicole, Lallas, Aimilio, Lebbé, Celeste, Lytvynenko, Bohdan, Malvehy, Josep, Moreno-Ramirez, David, Nathan, Paul, Pellacani, Giovanni, Saiag, Philippe, Stratigos, Alexander J, Van Akkooi, Alexander C J, Vieira, Ricardo, Zalaudek, Iri, and Lorigan, Paul
Subjects: Cancer Research, Sequential digital, Consensus, Skin Neoplasms, Follow-up examinations, [SDV]Life Sciences [q-bio], Consensu, Mutation testing, NEEDLE-ASPIRATION-CYTOLOGY, Primary diagnosis, MALIGNANT-MELANOMA, AJCC classification, Positron Emission Tomography Computed Tomography, Dermatoscopy, Humans, MELANOCYTIC NEVI, Follow-up examination, Imaging diagnostic, Melanoma, SENTINEL-NODE BIOPSY, ComputingMilieux_MISCELLANEOUS, Primary diagnosi, AMERICAN JOINT COMMITTEE, Neoplasm Staging, Manchester Cancer Research Centre, ResearchInstitutes_Networks_Beacons/mcrc, Confocal reflectance microscopy, Cutaneous melanoma, Imaging diagnostics, Sequential digital dermatoscopy, Total body photography, Neoplasm Recurrence, Local, [SDV] Life Sciences [q-bio], ACRAL LENTIGINOUS MELANOMA, Neoplasm Recurrence, Oncology, Local, TOTAL-BODY PHOTOGRAPHY, REFLECTANCE CONFOCAL MICROSCOPY, Settore MED/35 - MALATTIE CUTANEE E VENEREE, FOLLOW-UP, Human
Abstract: International audience; Cutaneous melanoma (CM) is potentially the most dangerous form of skin tumor and causes 90% of skin cancer mortality. A unique collaboration of multi-disciplinary experts from the European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organization for Research and Treatment of Cancer (EORTC) was formed to make recommendations on CM diagnosis and treatment, based on systematic literature reviews and the experts' experience. The diagnosis of melanoma can be made clinically and shall always be confirmed with dermatoscopy. If a melanoma is suspected, a histopathological examination is always required. Sequential digital dermatoscopy and full body photography can be used in high-risk patients to improve the detection of early melanoma. Where available, confocal reflectance microscopy can also improve clinical diagnosis in special cases. Melanoma shall be classified according to the 8th version of the American Joint Committee on Cancer classification. Thin melanomas up to 0.8 mm tumor thickness do not require further imaging diagnostics. From stage IB onwards, examinations with lymph node sonography are recommended, but no further imaging examinations. From stage IIC onwards whole-body examinations with computed tomography (CT) or positron emission tomography CT (PET-CT) in combination with brain magnetic resonance imaging are recommended. From stage III and higher, mutation testing is recommended, particularly for BRAF V600 mutation. It is important to provide a structured follow-up to detect relapses and secondary primary melanomas as early as possible. There is no evidence to define the frequency and extent of examinations. A stage-based follow-up scheme is proposed which, according to the experience of the guideline group, covers the optimal requirements, but further studies may be considered. This guideline is valid until the end of 2024.
Published: 2022

10. Peace, not war in Ukraine or anywhere else, please

Author: Jean-Yves Lefrant, Romain Pirracchio, Dan Benhamou, Marc-Olivier Fischer, Rosanna Njeim, Bernard Allaouchiche, Sophie Bastide, Matthieu Biais, Lionel Bouvet, Olivier Brissaud, Sorin J. Brull, Xavier Capdevila, Nicola Clausen, Philippe Cuvillon, Christophe Dadure, Jean-Stéphane David, Bin Du, Sharon Einav, Victoria Eley, Patrice Forget, Tomoko Fujii, Anne Godier, Dean P. Gopalan, Sophie Hamada, Ahmed Hasanin, Olivier Joannes-boyau, Sébastien Kerever, Éric Kipnis, Kerstin Kolodzie, Ruth Landau, Arthur Le Gall, Morgan Le Guen, Matthieu Legrand, Emmanuel Lorne, Frédéric J. Mercier, Nicolas Mongardon, Sheila Myatra, Armelle Nicolas-Robin, Mark John Peters, Hervé Quintard, Jordi Rello, Philippe Richebé, Jason Alexander Roberts, Antoine Rocquilly, Filippo Sanfilippo, Antoine Schneider, Mircea T. Sofonea, Francis Veyckemans, Paul Zetlaoui, Ahed Zeidan, Laurent Zieleskiewicz, Marzena Zielinska, Britta Von Ungern-Sternberg, Osama Abou Arab, Alice Blet, Fanny Bounes, Matthieu Boisson, Anaïs Caillard, Aude Carillion, Thomas Clavier, Denis Frasca, Arthur James, Stéphanie Sigaut, Sacha Rozencwajg, Pierre Albaladejo, Hervé Bouaziz, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Initial MAnagement and prevention of acute orGan failures IN critically ill patiEnts (IMAGINE), Université de Montpellier (UM), Société française d'anesthésie et de réanimation (SFAR), SFAR, University of California [San Francisco] (UC San Francisco), University of California (UC), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Département d'anesthésiologie [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), Hospices Civils de Lyon (HCL), CHU Bordeaux [Bordeaux], Mayo Clinic [Jacksonville], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Odense University Hospital (OUH), Unité de réanimation médicale [CHU de Carémeau, Nîmes], Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Peking Union Medical College Hospital [Beijing] (PUMCH), The Hebrew University of Jerusalem (HUJ), University of Queensland [Brisbane], University of Aberdeen, The Jikei University School of Medicine, 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), University of KwaZulu-Natal [Durban, Afrique du Sud] (UKZN), Cairo University - Faculty of Medicine, Service de Réanimation Médicale [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Hôpital Pellegrin, Département d’Anesthésie-Réanimation-SMUR [Hôpital Lariboisière], Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal, 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, CHU Lille, Columbia University Medical Center (CUMC), Columbia University [New York], CHU Pontchaillou [Rennes], Hôpital Foch [Suresnes], Simplification des soins chez les patients complexes - UR UPJV 7518 (SSPC), Université de Picardie Jules Verne (UPJV), Clinique du Millénaire - Oc Santé [Montpellier], Oc Santé [Montpellier], AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Homi Bhabha National Institute (HBNI), Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Great Ormond Street Hospital for Children NHS Foundation Trust [London, UK] (GOSHC), Centre Hospitalier Universitaire de Nice (CHU Nice), Universitat Internacional de Catalunya [Barcelona] (UIC), Hôpital Maisonneuve-Rosemont, Service des Urgences [CHU Nantes], Hôtel-Dieu de Nantes, Università degli studi di Catania = University of Catania (Unict), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM), Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), King Faisal Specialist Hospital and Resarch Centre [Riyadh, Saudi Arabia] (KFSHRC), Service Anesthésie et Réanimation [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Wrocław Medical University, The University of Western Australia (UWA), CHU Amiens-Picardie, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Hôpital de la Croix-Rousse [CHU - HCL], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service SAMU-SMUR [CHU Toulouse], Pôle Médecine d'urgences [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Pharmacologie des anti-infectieux et antibiorésistance (PHAR2), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des urgences [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), 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), 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 réanimation médicale [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), 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), MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR des Sciences Pharmaceutiques et Biologiques (Nantes Univ - UFR Pharmacie), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Hôpital Beaujon [AP-HP], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes (UGA), Service de Réanimation Médicale [CHRU Nancy], and Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)
Subjects: Warfare, Anesthesiology and Pain Medicine, MESH: Humans, MESH: Warfare, MESH: Ukraine, ARTICLE CLINIQUE, Humans, General Medicine, Critical Care and Intensive Care Medicine, Ukraine, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; War is back in Europe. With all its horrific pictures and live videos.In its report issued on the 24th of March 2022, the World Health Organization (WHO) [1] states that the Ukrainian conflict has involved 18 million persons so far, with 3.4 million refugees in bordering countries and 6.4 million persons internally displaced (Fig. 1). In this report, 1,035 deaths and 1,650 civilian injuries were reported in Ukraine without any reported data from Russia.
Published: 2022

11. LAMP2A regulates the loading of proteins into exosomes

Author: José C. Ramalho, Ana Sofia Carvalho, Henrique Girão, Petra Pintado, Paulo Pereira, Ana Soares, Joao Vasco Ferreira, Guillaume van Niel, Rune Matthiesen, Hans Christian Beck, Catarina Máximo Carvalho, Mónica Zuzarte, Maria Helena Cardoso, NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM), Centro de Estudos de Doenças Crónicas (CEDOC), Martinez Rico, Clara, Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Odense University Hospital (OUH), University of Coimbra [Portugal] (UC), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), GHU Paris Psychiatrie et Neurosciences, Centre Hospitalier Sainte Anne [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Endosome, BIOGENESIS, Cell Communication, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Exosomes, Exosome, Extracellular Vesicles, SYNTENIN, Lysosomal-Associated Membrane Protein 2, TSG101, LYSOSOMES, Transcription factor, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, EXTRACELLULAR VESICLE, Multidisciplinary, Endosomal Sorting Complexes Required for Transport, Chemistry, DEGRADATION, Microvesicles, Autophagic Punctum, Cell biology, Cytosol, HIF1A, Membrane protein, SECRETION, Signal Transduction
Abstract: Exosomes are extracellular vesicles of endosomal origin released by virtually all cell types across metazoans. Exosomes are active vehicles of intercellular communication and can transfer lipids, RNAs and proteins between different cells, tissues or organs. However, the mechanisms that regulate the selective loading of cytosolic proteins into these vesicles are still largely unknow. Here we describe a mechanism whereby proteins containing a pentapeptide sequence, biochemically related to the KFERQ-motif, are loaded into a subpopulation of exosomes in a process that is dependent on the membrane protein LAMP2A. Moreover, this mechanism is independent of the ESCRT machinery components TSG101 and VPS4b and dependent on HSC70, CD63, Alix, Syntenin-1, Rab31 and ceramides. The transcription factor and master regulator of hypoxia HIF1A is loaded into exosomes by this mechanism to transport hypoxia signaling to normoxic cells. Additionally, by tagging fluorescent proteins with KFERQ-like sequences we were able to follow inter-organ transfer of exosomes in zebrafish larvae. Our findings identify LAMP2A as a key component in exosome biogenesis while opening new avenues for exosome engineering by allowing the loading of bioactive proteins by tagging them with KFERQ-like motifs.
Published: 2022

12. European interdisciplinary guideline on invasive squamous cell carcinoma of the skin: Part 1. epidemiology, diagnostics and prevention

Author: Stratigos, Alexander J, Garbe, Claus, Dessinioti, Clio, Lebbe, Celeste, Bataille, Veronique, Bastholt, Lars, Dreno, Brigitte, Fargnoli, Maria Concetta, Forsea, Ana Maria, Frenard, Cecille, Harwood, Catherine Α, Hauschild, Axel, Hoeller, Christoph, Kandolf-Sekulovic, Lidija, Kaufmann, R, Kelleners-Smeets, Nicole Wj, Malvehy, Josep, Del Marmol, Veronique, Middleton, Mark R, Moreno-Ramirez, David, Pellecani, Giovanni, Peris, Ketty, Saiag, Philippe, van den Beuken-van Everdingen, Marieke H J, Vieira, Ricardo, Zalaudek, Iris, Eggermont, Alexander M M, Grob, Jean-Jacques, European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organization for Research and Treatment of Cancer (EORTC), National and Kapodistrian University of Athens (NKUA), Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), North & East Hertfordshire NHS Trust [Northwood, UK], Odense University Hospital (OUH), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), University of L'Aquila [Italy] (UNIVAQ), University of Medicine and Pharmacy 'Carol Davila' Bucharest (UMPCD), Queen Mary University of London (QMUL), Kiel University, Medizinische Universität Wien = Medical University of Vienna, Military Medical Academy [Belgrade, Serbia] (2MA), Frankfurt University Hospital, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), CIBER de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III [Madrid] (ISC), Université libre de Bruxelles (ULB), Hôpital Erasme [Bruxelles], University of Oxford, Hospital Universitario Virgen Macarena [Sevilla, Spain] (HUVM), University - Hospital of Modena and Reggio Emilia [Modena, Italy], Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Istituto Neurologico Mediterraneo (NEUROMED I.R.C.C.S.), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA)-University of Naples Federico II = Università degli studi di Napoli Federico II, Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, Hôpital Ambroise Paré [AP-HP], University Veterinary Hospital [Coimbra, Portugal], Università degli studi di Trieste = University of Trieste, Princess Máxima Center for Pediatric Oncology, Assistance Publique - Hôpitaux de Marseille (APHM), Aix Marseille Université (AMU), Novartis Les Laboratories Pierre Fabre Sanofi Bristol-Myers Squibb, BMS Pfizer Amgen Roche LEO Pharma Research Foundation Cilag Merck Meso Scale Diagnostics, MSD Genentech, The guidelines were supported by grants from the EADO for the guideline meetings. The authors did this work on a voluntary basis and did not receive any honorarium or reimbursements. Guidelines development group members stated their conflicts of interest in the relevant section., Dr. Stratigos reports personal fees and/or research support from Novartis , Roche , BMS , Abbvie , Sanofi , Regeneron , Genesis Pharma , outside the submitted work. Dr. Garbe reports personal fees from Amgen , personal fees from MSD , grants and personal fees from Novartis , grants and personal fees from NeraCare, grants and personal fees from BMS , personal fees from Pierre Fabre , personal fees from Philogen, grants and personal fees from Roche , grants and personal fees from Sanofi , outside the submitted work. Dr. Dessinioti has nothing to disclose. Dr. Lebbe reports grants and personal fees from Bristol-Myers Squibb , personal fees from MSD , personal fees from Novartis , personal fees from Amgen , grants and personal fees from Roche , personal fees from Avantis Medical Systems, personal fees from Pierre Fabre , personal fees from Pfizer , personal fees from Incyte, outside the submitted work. Dr. Bataille reports personal fees from Novartis , personal fees from Merck MSD , outside the submitted work. Dr. Bastholt reports personal fees for advisory board activity: BMS , Roche , Novartis , Pierre-Fabre, Astra Zeneca, InCyte, MSD / Merck , Bayer . Dr. Dréno reports grants and personal fees from BMS , personal fees from MSD , grants and personal fees from Roche , grants and personal fees from Fabre, grants and personal fees from Sanofi , outside the submitted work. Dr. Fargnoli reports grants and personal fees from Almirall, grants and personal fees from Leo Pharma, personal fees from Janssen, grants and personal fees from Novartis , personal fees from Lilly , grants and personal fees from Sanofi , personal fees from UCB , grants and personal fees from Abbvie , personal fees from Celgene , personal fees from Pierre Fabre , grants and personal fees from Galderma , personal fees from Mylan, personal fees from Medac Pharma, personal fees from Roche , personal fees from Sun Pharma , outside the submitted work. Dr. Forsea reports scientific consultant/speaker fee from Novartis , Leo Pharma, Solartium, Pierre-Fabre, outside the submitted work. Dr. Frenard has nothing to disclose. Dr. Harwood reports institutional research grants and honoraria from Sanofi , Novartis , Merck , Pfizer , Galderma , MEDA, Almirall, Pellepharm, Leo Pharma, CERIES. Dr. Hauschild reports honoraria and/or research grants from: Almirall, BMS , Roche , Novartis , Pierre-Fabre, Sunpharma, MerckSerono, SanofiAventis, Regeneron , MSD / Merck , Philogen, OncoSec outside the submitted work. Dr. Hoeller reports grants and personal fees from Amgen , personal fees from BMS , personal fees from MSD , personal fees from Novartis , personal fees from Pierre Fabre , personal fees from Roche , personal fees from Sanofi , personal fees from Incyte, outside the submitted work. Dr. Kandolf-Sekulovic reports speakers’ honoraria for Roche, Novartis, MSD, BMS, Janssen outside the submitted work. Dr. Kaufmann reports institutional research grants (clinical trials) from: AbbVie , Amgen , Biontech, BMS , Celgene , Galderma , Janssen, Leo, Lilly , Merck , MSD , Novartis , Pierre Fabre , Pfizer , Regeneron , Roche , Wyeth . Advisory Board and Honoraria from Merz, Roche, Novartis. Dr. Kelleners-Smeets reports grants from Netherlands Organization for Health Research and Development, other from Janssen-Cilag, other from AbbVie , other from Galderma , outside the submitted work. Dr. Malvehy reports research grants from Almirall, ISDIN, Leo Pharma, Galderma , GSK , Cantabria, participation in advisory board meetings for Almirall, Sunpharma, BMS , Roche , Novartis , Pierre-Fabre. Dr. del Marmol reports personal fees from MSD , from BMS , personal fees from Sanofi , grants and personal fees from ABVIE, grants from Jansen, outside the submitted work. Dr. Middleton reports personal fees and/or grants from Amgen , Roche , Astrazeneca, GSK , Novartis , Immunocore, BMS , Eisai and Merck . Institutional funding from Millennium, Vertex, Pfizer , Regeneron , TCBiopharma, BiolineRx, Replimune, outside the submitted work. Dr. Moreno-Ramírez has nothing to disclose. Dr. Pellecani reports grants from university of modena and reggio emilia, during the conduct of the study, grants from novartis, grants and personal fees from almirall, grants from leo pharma, from null, outside the submitted work. Dr. Peris reports honoraria for advisory board and grants from AbbVie , Almirall, Biogen Celgene , Lilly , Galderma , Leo Pharma, Novartis , Roche , Sanofi , Sun Pharma , Sandoz outside the submitted work. Dr. Saiag reports honoraria for advisory board and grants from Amgen , Bristol-Myers Squibb , MSD , Merck-Serono, Novartis , Pfizer , Roche- Genentech , Pierre Fabre , and Sanofi , outside the submitted work. Dr. van den Beuken-van Everdingen has nothing to disclose. Dr. Vieira has nothing to disclose. Dr. Zalaudek reports honoraria and advisory board and grants from Sanofi , Sun Pharma , Novartis , Galderma , Roche , Celgene , Almirall, Leofarma, Mylan, Difa Cooper, Cieffe Labs, La Roche Posay, Pierre Fabre . Dr. Eggermont reports over the last 5 years personal fees as a consultant advisor for Biocad, BioInvent, Bristol Myers Squibb ( BMS ), CatalYm, Ellipses, Glaxo Smith Kline ( GSK ), HalioDX, Incyte, IO Biotech, ISA Pharmaceuticals, Merck Sharpe & Dohme ( MSD ), Novartis , Pfizer , Polynoma, Regeneron , Sanofi , Sellas, SkylineDx. Dr. Grob reports personal fees for advisory board and as speaker from Amgen , Roche , GSK , Novartis , BMS , Pierre fabre, Merck , Sanofi , Merck , Pfizer outside the submitted work., European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organization for Research and Treatment of Cancer (EORTC), HAL UVSQ, Équipe, Dermatologie, MUMC+: MA Dermatologie (9), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, RS: MHeNs - R3 - Neuroscience, MUMC+: TPZ Palliatieve Zorg (9), Stratigos, A. J., Garbe, C., Dessinioti, C., Lebbe, C., Bataille, V., Bastholt, L., Dreno, B., Fargnoli, M. C., Forsea, A. M., Frenard, C., Harwood, C. Alpha., Hauschild, A., Hoeller, C., Kandolf-Sekulovic, L., Kaufmann, R., Kelleners-Smeets, N. W., Malvehy, J., del Marmol, V., Middleton, M. R., Moreno-Ramirez, D., Pellecani, G., Peris, K., Saiag, P., van den Beuken-van Everdingen, M. H. J., Vieira, R., Zalaudek, I., Eggermont, A. M. M., Grob, J. -J., Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)
Subjects: 0301 basic medicine, Cancer Research, Skin Neoplasms, Staging, Medical Oncology, Palpation, Imaging, Low-risk, 0302 clinical medicine, Protective Clothing, Metastatic cSCC, Positron Emission Tomography Computed Tomography, Diagnosis, Epidemiology, Societies, Medical, AMERICAN JOINT COMMITTEE, Skin, Ultrasonography, Invasive cutaneous squamous cell carcinoma, medicine.diagnostic_test, NONSTEROIDAL ANTIINFLAMMATORY DRUGS, High-risk common primary cSCC, RANDOMIZED CONTROLLED-TRIAL, Prognosis, Magnetic Resonance Imaging, 3. Good health, LYMPH-NODE BIOPSY, Oncology, 030220 oncology & carcinogenesis, Carcinoma, Squamous Cell, Sunlight, Settore MED/35 - MALATTIE CUTANEE E VENEREE, Diagnosi, medicine.medical_specialty, Consensus, Prognosi, Sentinel lymph node, Locally advanced Cscc, Prevention, Dermatology, Humans, Lymph Nodes, Neoplasm Staging, Patient Education as Topic, Risk Assessment, Sunscreening Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, Physical examination, PERINEURAL INVASION, 03 medical and health sciences, BASAL-CELL, [SDV.CAN] Life Sciences [q-bio]/Cancer, Medical, Biopsy, medicine, CANCER PREVENTION, ORGAN TRANSPLANT RECIPIENTS, business.industry, Carcinoma, Cancer, Magnetic resonance imaging, Guideline, medicine.disease, Cancérologie, HIGH-RISK, 030104 developmental biology, Squamous Cell, SUN PROTECTION, Societies, business
Abstract: Invasive cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers in the white populations, accounting for 20% of all cutaneous malignancies. Factors implicated in cSCC etiopathogenesis include ultraviolet radiation exposure and chronic photoaging, age, male sex, immunosuppression, smoking and genetic factors. A collaboration of multidisciplinary experts from the European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organisation of Research and Treatment of Cancer (EORTC) was formed to update recommendations on cSCC classification, diagnosis, risk stratification, staging and prevention, based on current literature, staging systems and expert consensus. Common cSCCs are typically indolent tumors, and most have a good prognosis with 5-year cure rates of greater than 90%, and a low rate of metastases (, SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2020

13. Sex-Specific Effects of Nutritional Supplements for Infants Born Early or Small: An Individual Participant Data Meta-Analysis (ESSENCE IPD-MA) II: Growth

Author: Luling Lin, Greg D. Gamble, Caroline A. Crowther, Frank H. Bloomfield, Massimo Agosti, Stephanie A. Atkinson, Augusto Biasini, Nicholas D. Embleton, Fernando Lamy Filho, Christoph Fusch, Maria L. Gianni, Hayriye Gözde Kanmaz Kutman, Winston Koo, Ita Litmanovitz, Colin Morgan, Kanya Mukhopadhyay, Erica Neri, Jean-Charles Picaud, Niels Rochow, Paola Roggero, Kenneth Stroemmen, Maw J. Tan, Francesco M. Tandoi, Claire L. Wood, Gitte Zachariassen, Jane E. Harding, CarMeN, laboratoire, University of Auckland [Auckland], Ospedale del Ponte [Varese, Italy], Universitá degli Studi dell’Insubria = University of Insubria [Varese] (Uninsubria), McMaster University [Hamilton, Ontario], Italian Association of Human Milk Banks [Milan, Italy] (AIBLUD), Newcastle University [Newcastle], Universidade Federal do Maranhão = Federal University of Maranhão (UFMA), Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Università degli Studi di Milano = University of Milan (UNIMI), Bilkent City Hospital = Ankara Şehir Hastanesi [Ankara, Turkey] (BCH), Wayne State University [Detroit], Meir Medical Center [Kfar Saba, Israel] (2MC), Liverpool Women's NHS Foundation Trust, Post Graduate Institute of Medical Education and Research [Chandigarh, India] (PGIMER), University of Bologna/Università di Bologna, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Oslo University Hospital [Oslo], Alder Hey Children's Hospital NHS Foundation Trust [Liverpool], Odense University Hospital (OUH), University of Southern Denmark (SDU), Lin L., Gamble G.D., Crowther C.A., Bloomfield F.H., Agosti M., Atkinson S.A., Biasini A., Embleton N.D., Filho F.L., Fusch C., Gianni M.L., Kutman H.G.K., Koo W., Litmanovitz I., Morgan C., Mukhopadhyay K., Neri E., Picaud J.-C., Rochow N., Roggero P., Stroemmen K., Tan M.J., Tandoi F.M., Wood C.L., Zachariassen G., and Harding J.E.
Subjects: Male, growth, [SDV]Life Sciences [q-bio], Growth, Sex Factor, macronutrient supplementation, Individual participants data meta-analysi, small-for-gestational-age infants, Follow-Up Studie, Body Mass Index, Sex Factors, systematic review, Bone Density, Humans, TX341-641, preterm infants, Infant Nutritional Physiological Phenomena, Dietary Supplement, Nutrition and Dietetics, Small-for-gestational-age infants, Nutrition. Foods and food supply, Small-for-gestational-age infant, Infant, Newborn, Individual participants data meta-analysis, Preterm infants, Macronutrient supplementation, Nutrients, Body Height, individual participants data meta-analysis, [SDV] Life Sciences [q-bio], Treatment Outcome, Preterm infant, Dietary Supplements, Infant, Small for Gestational Age, Systematic review, Female, Infant, Premature, Human, Nutrient, Food Science, Follow-Up Studies
Abstract: Neonatal nutritional supplements may improve early growth for infants born small, but effects on long-term growth are unclear and may differ by sex. We assessed the effects of early macronutrient supplements on later growth. We searched databases and clinical trials registers from inception to April 2019. Participant-level data from randomised trials were included if the intention was to increase macronutrient intake to improve growth or development of infants born preterm or small-for-gestational-age. Co-primary outcomes were cognitive impairment and metabolic risk. Supplementation did not alter BMI in childhood (kg/m2: adjusted mean difference (aMD) −0.11[95% CI −0.47, 0.25], p = 0.54; 3 trials, n = 333). Supplementation increased length (cm: aMD 0.37[0.01, 0.72], p = 0.04; 18 trials, n = 2008) and bone mineral content (g: aMD 10.22[0.52, 19.92], p = 0.04; 6 trials, n = 313) in infancy, but not at older ages. There were no differences between supplemented and unsupplemented groups for other outcomes. In subgroup analysis, supplementation increased the height z-score in male toddlers (aMD 0.20[0.02, 0.37], p = 0.03; 10 trials, n = 595) but not in females, and no significant sex interaction was observed (p = 0.21). Macronutrient supplementation for infants born small may not alter BMI in childhood. Supplementation increased growth in infancy, but these effects did not persist in later life. The effects did not differ between boys and girls.
Published: 2022

14. Sex-Specific Effects of Nutritional Supplements for Infants Born Early or Small: An Individual Participant Data Meta-Analysis (ESSENCE IPD-MA) I-Cognitive Function and Metabolic Risk

Author: Luling Lin, Greg D. Gamble, Caroline A. Crowther, Frank H. Bloomfield, Massimo Agosti, Stephanie A. Atkinson, Augusto Biasini, Nicholas D. Embleton, Mary S. Fewtrell, Fernando Lamy-Filho, Christoph Fusch, Maria L. Gianni, H. Gozde Kanmaz Kutman, Winston Koo, Ita Litmanovitz, Colin Morgan, Kanya Mukhopadhyay, Erica Neri, Jean-Charles Picaud, Niels Rochow, Paola Roggero, Atul Singhal, Kenneth Stroemmen, Maw J. Tan, Francesco M. Tandoi, Claire L. Wood, Gitte Zachariassen, Jane E. Harding, CarMeN, laboratoire, University of Auckland [Auckland], Ospedale del Ponte [Varese, Italy], McMaster University [Hamilton, Ontario], Italian Association of Human Milk Banks [Milan, Italy] (AIBLUD), Newcastle University [Newcastle], Great Ormond Street Institute of Child Health (UCL), University College of London [London] (UCL), Universidade Federal do Maranhão = Federal University of Maranhão (UFMA), Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Università degli Studi di Milano = University of Milan (UNIMI), Bilkent City Hospital = Ankara Şehir Hastanesi [Ankara, Turkey] (BCH), Wayne State University [Detroit], Meir Medical Center [Kfar Saba, Israel] (2MC), Liverpool Women's NHS Foundation Trust, Post Graduate Institute of Medical Education and Research [Chandigarh, India] (PGIMER), University of Bologna/Università di Bologna, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Institute of Child Health [London], Oslo University Hospital [Oslo], Alder Hey Children's Hospital NHS Foundation Trust [Liverpool], Odense University Hospital (OUH), University of Southern Denmark (SDU), Lin L., Gamble G.D., Crowther C.A., Bloomfield F.H., Agosti M., Atkinson S.A., Biasini A., Embleton N.D., Fewtrell M.S., Lamy-Filho F., Fusch C., Gianni M.L., Gozde Kanmaz Kutman H., Koo W., Litmanovitz I., Morgan C., Mukhopadhyay K., Neri E., Picaud J.-C., Rochow N., Roggero P., Singhal A., Stroemmen K., Tan M.J., Tandoi F.M., Wood C.L., Zachariassen G., and Harding J.E.
Subjects: Male, [SDV]Life Sciences [q-bio], macronutrient supplementation, Individual participants data meta-analysi, Cognition, Pregnancy, small-for gestational-age infants, Humans, TX341-641, Cognitive Dysfunction, Metabolic risk, preterm infants, cognitive function, Nutrition and Dietetics, Nutrition. Foods and food supply, Small-for gestational-age infant, Infant, Newborn, Parturition, Individual participants data meta-analysis, Preterm infants, Infant, Macronutrient supplementation, Small-for gestational-age infants, individual participants data meta-analysis, [SDV] Life Sciences [q-bio], metabolic risk, Preterm infant, Dietary Supplements, Infant, Small for Gestational Age, Systematic review, Female, Cognitive function, systematic review, Food Science
Abstract: Neonatal nutritional supplements are widely used to improve growth and development but may increase risk of later metabolic disease, and effects may differ by sex. We assessed effects of supplements on later development and metabolism. We searched databases and clinical trials registers up to April 2019. Participant-level data from randomised trials were included if the intention was to increase macronutrient intake to improve growth or development of infants born preterm or small-for-gestational-age. Co-primary outcomes were cognitive impairment and metabolic risk. Supplementation did not alter cognitive impairment in toddlers (13 trials, n = 1410; adjusted relative risk (aRR) 0.88 [95% CI 0.68, 1.13]; p = 0.31) or older ages, nor alter metabolic risk beyond 3 years (5 trials, n = 438; aRR 0.94 [0.76, 1.17]; p = 0.59). However, supplementation reduced motor impairment in toddlers (13 trials, n = 1406; aRR 0.76 [0.60, 0.97]; p = 0.03), and improved motor scores overall (13 trials, n = 1406; adjusted mean difference 1.57 [0.14, 2.99]; p = 0.03) and in girls not boys (p = 0.03 for interaction). Supplementation lowered triglyceride concentrations but did not affect other metabolic outcomes (high-density and low-density lipoproteins, cholesterol, fasting glucose, blood pressure, body mass index). Macronutrient supplementation for infants born small may not alter later cognitive function or metabolic risk, but may improve early motor function, especially for girls.
Published: 2021

15. Real-life practice of thyroid hormone use in hypothyroid and euthyroid patients: a detailed view from the THESIS questionnaire survey in France

Author: Buffet, C, Belin, L, Attanasio, R, Hegedüs, L, Nagy, EV, Papini, E, Perros, P, Leenhardt, L, Groupe de recherche clinique – Tumeurs Thyroïdiennes [CHU Pitié-Salpêtrière] (GRC-TT), 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), Odense University Hospital (OUH), University of Debrecen, Pontifical University 'Regina Apostolorum', and Royal Victoria Infirmary, Newcastle upon Tyne
Subjects: Liothyronine, sondage, Société Française d’Endocrinologie, Hypothyroidism, Euthyroïdie, Levothyroxine, French Endocrine Society, Lévothyroxine, Euthyroidism, Survey, Hypothyroïdie, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Aim: To describe practices of French physicians regarding thyroid hormone therapy, focusing on available LT4 formulations.Material and methods: Members of the French Endocrine Society (FES) and affiliated societies (the Endocrine Tumor Group, French College of Teachers of Endocrinology, Diabetes and Metabolic Diseases and the Union of Endocrinology, Diabetology, Metabolic Diseases and Nutrition Specialists) were invited to participate in an online survey.Results: 534 of the 2,094 persons contacted (25.5%) completed the survey and were included in the analysis. The vast majority (99.4%) reported that levothyroxine (LT4) is the treatment of choice for hypothyroidism. 7.1% and 14.2% of respondents respectively considered liothyronine (LT3) or a combination of LT4 and LT3 for the treatment of hypothyroidism, mainly when symptoms persisted despite achieving normal TSH concentrations with LT4 therapy. For 44% of respondents, thyroid hormone treatment is never indicated in euthyroid patients, while the remainder would consider treating euthyroid patients with a goiter growing over time (40.2%) and/or euthyroid women with positive anti-TPO antibodies and infertility (31.7%). LT4 tablets were the preferred LT4 formulation. A significant proportion of FES members expected no major clinical differences upon changing to formulations such as soft-gel capsules or liquid solutions, even in specific scenarios such as poor biochemical control or suspicion of malabsorption.Conclusion: The treatment of choice for hypothyroidism in France is LT4. LT3-based therapy is considered by some physicians in case of persistent symptoms of hypothyroidism despite normal TSH level. A significant proportion of respondents (66.0%) would consider treating euthyroid patients, contrary to the present state of knowledge. These outdated practices should be addressed by professional bodies such as the FES.; Objectifs: Décrire les pratiques des médecins français concernant l’utilisation thérapeutique des hormones thyroïdiennes, et notamment des formes galéniques disponibles pour la lévothyroxine (LT4).Matériel et méthodes: Les membres de la Société Française d’Endocrinologie (SFE) et de ses sociétés affiliées (le Groupe d’Etudes des Tumeurs Endocrines, le Collège des Enseignants en Endocrinologie, Diabétologie et Maladies Métaboliques et le Syndicat des médecins spécialistes en Endocrinologie, Diabétologie, Maladies Métaboliques et Nutrition) ont été invités à participer à un sondage en ligne.Résultats: Parmi les 2094 personnes contactées, 534 (25,5%) ont répondu et ont été inclus dans l’étude. Selon une très grande majorité d’entre eux (99,4%) la lévothyroxine (LT4) serait le traitement de choix pour l’hypothyroïdie. Respectivement 7,1% et 14,2% envisageraient d’utiliser la liothyronine (LT3) ou l’association de LT4 et LT3 pour l’hypothyroïdie, surtout en cas de symptômes persistants malgré un taux normal de TSH après traitement par LT4. Pour 44% des sondés, les traitements par hormones thyroïdiennes ne sont jamais indiqués pour les patients euthyroïdiens, alors que les autres pourraient éventuellement traiter un patient euthyroïdien avec goitre progressif (40,2%) et / ou une patiente euthyroïdienne infertile et positive pour le anticorps anti-TPO (31,7%). La forme galénique préférée pour la LT4 était sous forme de cachets. Un pourcentage important des membres de la SFE n’anticipait aucune différence clinique majeur si cette forme est remplacée, par exemple, par des capsules de gel mou ou par une solution liquide, même dans des cas spécifiques comme d’absence de contrôle biologique ou de soupçon de malabsorption.Conclusion: Le traitement de choix pour l’hypothyroïdie en France est la LT4. Certains confrères utilisent la LT3 en cas de symptômes persistants d’hypothyroïdie malgré un taux de TSH normal. Selon un pourcentage important des sondés (66.0%), il serait envisageable de mettre en place des traitements pour les patients euthyroïdiens, ce qui ne correspond pas à l’état actuel des connaissances. Les instances professionnelles comme la SFE devraient s’adresser à ces pratiques désuètes.
Published: 2021

16. Early Bacterial Identification among Intubated Patients with COVID-19 or Influenza Pneumonia: A European Multicenter Comparative Clinical Trial

Author: Anahita Rouzé, Ignacio Martin-Loeches, Pedro Povoa, Matthieu Metzelard, Damien Du Cheyron, Fabien Lambiotte, Fabienne Tamion, Marie Labruyere, Claire Boulle Geronimi, Ania Nieszkowska, Martine Nyunga, Olivier Pouly, Arnaud W. Thille, Bruno Megarbane, Anastasia Saade, Emili Diaz, Eleni Magira, Jean-François Llitjos, Catia Cilloniz, Iliana Ioannidou, Alexandre Pierre, Jean Reignier, Denis Garot, Louis Kreitmann, Jean-Luc Baudel, Muriel Fartoukh, Gaëtan Plantefeve, Alexandra Beurton, Pierre Asfar, Alexandre Boyer, Armand Mekontso-Dessap, Demosthenes Makris, Christophe Vinsonneau, Pierre-Edouard Floch, Nicolas Weiss, Adrian Ceccato, Antonio Artigas, Mathilde Bouchereau, Alain Duhamel, Julien Labreuche, Saad Nseir, Julien Poissy, Raphaël Favory, Sébastien Preau, Mercè Jourdain, Sean Boyd, Luis Coelho, Pierre Cuchet, Wafa Zarrougui, Déborah Boyer, Jean-Pierre Quenot, Mehdi Imouloudene, Charles-Edouard Luyt, Thierry van der Linden, Justine Bardin, Sebastian Voicu, Elie Azoulay, Gemma Goma, Frédéric Pene, Antoni Torres, Didier Thevenin, Stéphan Ehrmann, Laurent Argaud, Bertrand Guidet, Guillaume Voiriot, Damien Contou, Julien Le Marec, Julien Demiselle, David Meguerditchian, Keyvan Razazi, Vassiliki Tsolaki, Caroline Sejourne, Guillaume Brunin, Loïc Le Guennec, Luis Morales, CHU Lille, Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Trinity College Dublin, University of Barcelona, New University of Lisbon, Odense University Hospital (OUH), CHU Amiens-Picardie, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre hospitalier [Valenciennes, Nord], Endothélium, valvulopathies et insuffisance cardiaque (EnVI), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier [Douai, Nord], Institut de cardiologie [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 Hospitalier de Roubaix, Hôpital Saint Philibert [Lomme], Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), Centre hospitalier universitaire de Poitiers (CHU Poitiers), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Réanimation Médicale et Toxicologique [Hôpital Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hopital Saint-Louis [AP-HP] (AP-HP), Universitat Autònoma de Barcelona (UAB), National and Kapodistrian University of Athens (NKUA), Hôpital Cochin [AP-HP], Centre Hospitalier de Lens, Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Tenon [AP-HP], Centre Hospitalier Victor Dupouy, Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Bordeaux [Bordeaux], CHU Henri Mondor [Créteil], Groupe de recherche clinique CARMAS (Cardiovascular and Respiratory Manifestations of Acute lung injury and Sepsis) (CARMAS), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-CHU Henri Mondor [Créteil], Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), University of Thessaly [Larissa], Centre Hospitalier de Béthune (CH Béthune), GHT de l'Artois, Hôpital Duchenne, CH Boulogne sur Mer, 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 d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), coVAPid Study Group, CHU Henri Mondor, 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 Henri Mondor, and Mégarbane, Bruno
Subjects: Surviving Sepsis Campaign, medicine.medical_treatment, Disease, Critical Care and Intensive Care Medicine, medicine.disease_cause, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Mechanical ventilation, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, 030212 general & internal medicine, intensive care, Coronavirus, [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, Coinfection, Bacterial, virus diseases, Antimicrobial, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.TOX] Life Sciences [q-bio]/Toxicology, [SDV.TOX]Life Sciences [q-bio]/Toxicology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, influenza, Cohort study, Pulmonary and Respiratory Medicine, Adult, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), mechanical ventilation, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Intensive care, Internal medicine, Influenza, Human, Humans, bacterial, COVID-19/Pulmonary Infections, Retrospective Studies, business.industry, SARS-CoV-2, COVID-19, Original Articles, Pneumonia, Influenza, respiratory tract diseases, 030228 respiratory system, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, business
Abstract: International audience; Rationale: Early empirical antimicrobial treatment is frequently prescribed to critically ill patients with coronavirus disease (COVID-19) based on Surviving Sepsis Campaign guidelines.Objectives: We aimed to determine the prevalence of early bacterial identification in intubated patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia, as compared with influenza pneumonia, and to characterize its microbiology and impact on outcomes.Methods: A multicenter retrospective European cohort was performed in 36 ICUs. All adult patients receiving invasive mechanical ventilation >48 hours were eligible if they had SARS-CoV-2 or influenza pneumonia at ICU admission. Bacterial identification was defined by a positive bacterial culture within 48 hours after intubation in endotracheal aspirates, BAL, blood cultures, or a positive pneumococcal or legionella urinary antigen test.Measurements and Main Results: A total of 1,050 patients were included (568 in SARS-CoV-2 and 482 in influenza groups). The prevalence of bacterial identification was significantly lower in patients with SARS-CoV-2 pneumonia compared with patients with influenza pneumonia (9.7 vs. 33.6%; unadjusted odds ratio, 0.21; 95% confidence interval [CI], 0.15-0.30; adjusted odds ratio, 0.23; 95% CI, 0.16-0.33; P < 0.0001). Gram-positive cocci were responsible for 58% and 72% of coinfection in patients with SARS-CoV-2 and influenza pneumonia, respectively. Bacterial identification was associated with increased adjusted hazard ratio for 28-day mortality in patients with SARS-CoV-2 pneumonia (1.57; 95% CI, 1.01-2.44; P = 0.043). However, no significant difference was found in the heterogeneity of outcomes related to bacterial identification between the two study groups, suggesting that the impact of coinfection on mortality was not different between patients with SARS-CoV-2 and influenza.Conclusions: Bacterial identification within 48 hours after intubation is significantly less frequent in patients with SARS-CoV-2 pneumonia than patients with influenza pneumonia.Clinical trial registered with www.clinicaltrials.gov (NCT04359693).
Published: 2021

17. Guidelines for Biobanking of Bone Marrow Adipose Tissue and Related Cell Types: Report of the Biobanking Working Group of the International Bone Marrow Adiposity Society

Author: Stephanie Lucas, Michaela Tencerova, Benoit von der Weid, Thomas Levin Andersen, Camille Attané, Friederike Behler-Janbeck, William P. Cawthorn, Kaisa K. Ivaska, Olaia Naveiras, Izabela Podgorski, Michaela R. Reagan, Bram C. J. van der Eerden, Marrow Adiposity & Bone Lab - Adiposité Médullaire et Os - ULR 4490 (MABLab (ex-pmoi)), Université du Littoral Côte d'Opale (ULCO)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institute of Physiology [Prague], Czech Academy of Sciences [Prague] (CAS), School of Life Sciences [Lausanne], Ecole Polytechnique Fédérale de Lausanne (EPFL), Odense University Hospital (OUH), Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Queen's Medical Researche Institute, University of Edinburgh, University of Turku, Lausanne University Hospital, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Maine Medical Center Research Institute (MMCRI), and Erasmus University Medical Center [Rotterdam] (Erasmus MC)
Subjects: Endocrinology, Diabetes and Metabolism, Adipose tissue, Review, Tissue Banks, international research networks, cell isolation protocols, bone marrow adiposity, Diseases of the endocrine glands. Clinical endocrinology, Endocrinology, biobanking, SDG 3 - Good Health and Well-being, Bone Marrow, Patient information, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Medicine, Humans, clinical studies, Adiposity, Biological Specimen Banks, business.industry, bone marrow adipocytes, International community, RC648-665, Biobank, patient information, Biological materials, medicine.anatomical_structure, Adipose Tissue, Position paper, Engineering ethics, Bone marrow, business, Consent Forms, bone marrow stromal cells
Abstract: International audience; Over the last two decades, increased interest of scientists to study bone marrow adiposity (BMA) in relation to bone and adipose tissue physiology has expanded the number of publications using different sources of bone marrow adipose tissue (BMAT). However, each source of BMAT has its limitations in the number of downstream analyses for which it can be used. Based on this increased scientific demand, the International Bone Marrow Adiposity Society (BMAS) established a Biobanking Working Group to identify the challenges of biobanking for human BMA-related samples and to develop guidelines to advance establishment of biobanks for BMA research. BMA is a young, growing field with increased interest among many diverse scientific communities. These bring new perspectives and important biological questions on how to improve and build an international community with biobank databases that can be used and shared all over the world. However, to create internationally accessible biobanks, several practical and legislative issues must be addressed to create a general ethical protocol used in all institutes, to allow for exchange of biological material internationally. In this position paper, the BMAS Biobanking Working Group describes similarities and differences of patient information (PIF) and consent forms from different institutes and addresses a possibility to create uniform documents for BMA biobanking purposes. Further, based on discussion among Working Group members, we report an overview of the current isolation protocols for human bone marrow adipocytes (BMAds) and bone marrow stromal cells (BMSCs, formerly mesenchymal), highlighting the specific points crucial for effective isolation. Although we remain far from a unified BMAd isolation protocol and PIF, we have summarized all of these important aspects, which are needed to build a BMA biobank. In conclusion, we believe that harmonizing isolation protocols and PIF globally will help to build international collaborations and improve the quality and interpretation of BMA research outcomes.
Published: 2021

18. Efficacy and Safety of Rovalpituzumab Tesirine Compared With Topotecan as Second-Line Therapy in DLL3-High SCLC: Results From the Phase 3 TAHOE Study

Author: Ilié, Marius, Mazières, Julien, Chamorey, Emmanuel, Heeke, Simon, Benzaquen, Jonathan, Thamphya, Brice, Boutros, Jacques, Tiotiu, Angélica, Fayada, Julien, Cadranel, Jacques, Poudenx, Michel, Moro-Sibilot, Denis, Barlesi, Fabrice, Thariat, Juliette, Clément-Duchêne, Christelle, Tomasini, Pascale, Hofman, Véronique, Marquette, Charles-Hugo, Hofman, Paul, Israel-Biet, Dominique, Pison, Christophe, Lantuejoul, Sylvie, Stephanov, Olivier, Juliette, Meyzenc, Mendozat, Christophe, Zaidi, Manel, Coulouvrat, Sandra, Col, Edwige, Chanez, Pascal, Greillier, Laurent, Mascaux, Céline, Jourdan, Sandrine, Roger, Aurélie, Biemar, Julie, Randriamampionona, Rondro, Chabot, François, Vignaud, Jean-Michel, Lacomme, Stéphanie, Lomazzi, Sandra, Laurent, Carine, Bulsei, Xavier, Bischoff, Laura, Rakotonirina, Raymond, Layouni, Mehdi, Deslee, Gaëtan, Mal, Hervé, Kessler, Romain, Vergnon, Jean-Michel, Pelissier, Isabelle, Cuvelier, Antoine, Bourdin, Arnaud, Jounieaux, Vincent, Roche, Nicolas, Jouneau, Stéphane, Bonniaud, Philippe, Scherpereel, Arnaud, Mornex, Jean François, Steenhouwer, François, Leroy, Sylvie, Marquette, Charles Hugo, Mazzette, Andrea, Padovani, Bernard, Long-Mira, Elodie, Lassalle, Sandra, Pradelli, Johanna, Martinez, Estelle, Habault, Marine, Bonnard, Mélanie, Moutarde, Julie, Yatimi, Rachida, Labsi, Hakima, Gazoppi, Loïc, Lpce, Tumorothèque, Griffonnet, Jennifer, Fontaine, Maureen, Guillemart, Ariane, Butori, Catherine, Selva, Eric, Otto, Josiane, Hebert, Christophe, Botchiellini, Delphine, Boudouf, Soukaina, Menier, Margaux, Occeli, Estelle, Bellentani, Sophie, Pion, Carine, Fournier, Elodie, Gervais, Radj, Hamond, Karim, Marchand-Adam, Sylvain, Plantier, Laurent, Fajolle, Gaelle, Rayez, Mélanie, Fallet, Vincent, Wislez, Marie, Antoine, Martine, Cote, Jean-François, Chaabane, Nouha, Ruppert, Anne Marie, Bertrand, Eliane, Rodenas, Anita, Pontdeme, Gwenaëlle, Mathiot, Nathalie, Ribert, Tamazouzt, Guibert, Nicolas, Rouviere, Damien, Bousquet, Emilie, Bigay-Game, Laurence, Hermant, Christophe, Plat, Gavin, Rouquette, Isabelle, Evrard, Solène, Gouin, Sandrine, Clermont, Estelle Taranchon, Dormoy, Inge, Coulomb, Christelle, Pradine, Anne, Lambert, Véronique, Laborde, Lilian, Castelnau, Olivier, University of Manchester [Manchester], Hôpital du Sacré-Coeur de Montréal, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Marseille (APHM), Yonsei University College of Medicine [Séoul, Corée du Sud], August Pi i Sunyer Biomedical Research Institute - IDIBAPS [Barcelona, Spain], Hospital de la Santa Creu i Sant Pau, University Hospitals Leuven [Leuven], National and Kapodistrian University of Athens (NKUA), Odense University Hospital (OUH), Oregon Health and Science University [Portland] (OHSU), Kyushu University, Hacettepe University = Hacettepe Üniversitesi, University of Copenhagen = Københavns Universitet (UCPH), University of Groningen [Groningen], Abbvie Inc. [North Chicago], Asklepios Klinikum Uckermark GmbH, Méthodes computationnelles pour la prise en charge thérapeutique en oncologie : Optimisation des stratégies par modélisation mécaniste et statistique (COMPO), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Cancérologie de Marseille (CRCM), and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut Paoli-Calmettes
Subjects: 0301 basic medicine, Pulmonary and Respiratory Medicine, Oncology, medicine.medical_specialty, medicine.medical_treatment, CELL LUNG-CANCER, Population, Peripheral edema, Phases of clinical research, [SDV.CAN]Life Sciences [q-bio]/Cancer, Delta-like protein 3, Rovalpituzumab tesirine, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, DRUG, education, ComputingMilieux_MISCELLANEOUS, Chemotherapy, education.field_of_study, Small cell lung cancer, business.industry, Hazard ratio, Confidence interval, 030104 developmental biology, 030220 oncology & carcinogenesis, Topotecan, medicine.symptom, business, medicine.drug
Abstract: INTRODUCTION: DLL3, an atypical Notch ligand, is expressed in SCLC tumors but is not detectable in normal adult tissues. Rovalpituzumab tesirine (Rova-T) is an antibody-drug conjugate containing a DLL3-targeting antibody tethered to a cytotoxic agent pyrrolobenzodiazepine by means of a protease-cleavable linker. The efficacy and safety of Rova-T compared with topotecan as second-line therapy in patients with SCLC expressing high levels of DLL3 (DLL3-high) was evaluated. METHODS: The TAHOE study was an open-label, two-to-one randomized, phase 3 study comparing Rova-T with topotecan as second-line therapy in DLL3-high advanced or metastatic SCLC. Rova-T (0.3 mg/kg) was administered intravenously on day 1 of a 42-day cycle for two cycles, with two additional cycles available to patients who met protocol-defined criteria for continued dosing. Topotecan (1.5 mg/m2) was administered intravenously on days 1 to 5 of a 21-day cycle. The primary end point was overall survival (OS). RESULTS: Patients randomized to Rova-T (n = 296) and topotecan (n = 148) were included in the efficacy analyses. The median age was 64 years, and 77% had the extensive disease at initial diagnosis. The median OS (95% confidence interval) was 6.3 months (5.6-7.3) in the Rova-T arm and 8.6 months (7.7-10.1) in the topotecan arm (hazard ratio, 1.46 [95% confidence interval: 1.17-1.82]). An independent data monitoring committee recommended that enrollment be discontinued because of the shorter OS observed with Rova-T compared with topotecan. Safety profiles for both drugs were consistent with previous reports. CONCLUSIONS: Compared with topotecan, which is the current standard second-line chemotherapy, Rova-T exhibited an inferior OS and higher rates of serosal effusions, photosensitivity reaction, and peripheral edema in patients with SCLC. A considerable unmet therapeutic need remains in this population. ispartof: JOURNAL OF THORACIC ONCOLOGY vol:16 issue:9 pages:1547-1558 ispartof: location:United States status: published
Published: 2021

19. Differential localization patterns of Claudin 10, 16 and 19 in human, mouse, and rat renal tubular epithelia

Author: Dominik N. Müller, Karsten Skjødt, Camille Griveau, Reza Zamani, Gaëlle Brideau, Elsa Ferriere, Caroline Prot-Bertoye, Lydie Cheval, Pascal Houillier, Loïc Lievre, Lucile Figueres, Tilman Breiderhoff, Floriane Arbaretaz, Niels Marcussen, Henrik Dimke, Kevin Garbin, Patrick Bruneval, 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), 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), Physiologie rénale et tubulopathies = Renal Physiology and tubulopathies [CRC], Centre National de la Recherche Scientifique (CNRS)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École pratique des hautes études (EPHE), University of Southern Denmark (SDU), Odense University Hospital (OUH), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], and Brideau, Gaëlle
Subjects: kidney, Physiology, tight junction, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Immunofluorescence, Epithelium, Tight Junctions, 03 medical and health sciences, Mice, immunolocalization, 0302 clinical medicine, Cortex (anatomy), medicine, Animals, Humans, Claudin, 030304 developmental biology, 0303 health sciences, Kidney, Tight junction, medicine.diagnostic_test, Chemistry, urogenital system, Immunohistochemistry, Cell biology, Rats, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Kidney Tubules, thick ascending limb, Paracellular transport, Claudins, Research Article
Abstract: International audience; Functional properties of the paracellular pathway depend critically on the set of claudins (CLDN) expressed at the tight junction. Two syndromes are causally linked to loss-of-function mutations of claudins: hypohidrosis, electrolyte imbalance, lacrimal gland dysfunction, ichthyosis, and xerostomia (HELIX) syndrome caused by genetic variations in the CLDN10 gene and familial hypomagnesemia with hypercalciuria and nephrocalcinosis caused by genetic variations in the CLDN16 or CLDN19 genes. All three genes are expressed in the kidney, particularly in the thick ascending limb (TAL). However, localization of these claudins in humans and rodents remains to be delineated in detail. We studied the segmental and subcellular expression of CLDN10, CLDN16, and CLDN19 in both paraffin-embedded and frozen kidney sections from the adult human, mouse, and rat using immunohistochemistry and immunofluorescence, respectively. Here, CLDN10 was present in a subset of medullary and cortical TAL cells, localizing to basolateral domains and tight junctions in human and rodent kidneys. Weak expression was detected at the tight junction of proximal tubular cells. CLDN16 was primarily expressed in a subset of TAL cells in the cortex and outer stripe of outer medulla, restricted to basolateral domains and tight junctional structures in both human and rodent kidneys. CLDN19 predominantly colocalized with CLDN16 in tight junctions and basolateral domains of the TAL but was also found in basolateral and junctional domains in more distal sites. CLDN10 expression at tight junctions almost never overlapped with that of CLND16 and CLDN19, consistent with distinct junctional pathways with different permeation profiles in both human and rodent kidneys.NEW & NOTEWORTHY This study used immunohistochemistry and immunofluorescence to investigate the distribution of claudin 10, 16, and 19 in the human, mouse, and rat kidney. The findings showed distinct junctional pathways in both human and rodent kidneys, supporting the existence of different permeation profiles in all species investigated.
Published: 2021

20. ARIA‐EAACI care pathways for allergen immunotherapy in respiratory allergy

Author: Bousquet, Jean, Pfaar, Oliver, Agache, Ioana, Bedbrook, Anna, Akdis, Cezmi A, Canonica, Giorgio Walter, Chivato, Tomas, Al-Ahmad, Mona, Rasib, A. H. Abdul, Ansotegui, Ignacio J, Bachert, Claus, Soto-Martinez, Manuel, Laune, Daniel, Casale, Tomas, Levin, Michael, Larenas-Linnemann, Désirée, Samolinski, Boleslaw, Lodrup Carlsen, Karin C, O'Mahony, Liam, Lombardi, Carlo, Riggioni, Carmen, Hossny, Elham, Barata, Luís Taborda, Lourenço, Olga, Devillier, Philippe, Mahboub, Bassam, Malling, Hans-Jørgen, Sheikh, Aziz, Manning, Patrick, Passalacqua, Giovanni, Marshall, Gailen D, Sanchez-Borges, Mario, Toppila-Salmi, Sanna, Melén, Erik, Fokkens, Wytske J, Meltzer, Eli O, Miculinic, Neven, Soto-Quiros, Manuel, Milenkovic, Branislava, Roberts, Graham, Ohta, Ken, Scichilone, Nicola, Moin, Mostafa, Odemyr, Mikaëla, Montefort, Stephen, Almeida, Mário Morais, Bom, Ana Todo, Mortz, Charlotte G, Serpa, Faradiba S, Patella, Vincenzo, Sova, Milan, Mösges, Ralph, Mullol, Joaquim, Namazova Baranova, Leyla, Tsiligianni, Ioanna, Neffen, Hugo, Bjermer, Leif, Rodriguez-Gonzales, Monica, Torres, Maria J, Okamoto, Yoshitaka, Okubo, Kimi, Pajno, Giovanni B, Baharuddin, Abdullah, Cecchi, Lorenzo, Sastre, Joaquin, Untersmayr, Eva, Pawankar, Ruby, Pham-Thi, Nhân, Plavec, Davor, Cardona, Victoria, Dokic, Dejan, Sisul, Juan Carlos, Rosario, Nelson, Rottem, Menachem, Rouadi, Philip W, Del Giacco, Stefano, Fonseca, Joao A, Schwarze, Jürgen, Scadding, Glenis K, Shamji, Mohamed H, Schmid-Grendelmeier, Peter, Niedoszytko, Marek, Valentin-Rostan, Marylin, Sofiev, Mikhail, Solé, Dirceu, Sooronbaev, Talant, Palkonen, Susanna, Urrutia-Pereira, Marilyn, Skypala, Isabel, Suppli-Ulrik, Charlotte, Bonini, Matteo, Popov, Todor A, Tomazic, Peter-Valentin, Valero, Antonio, Cepeda Sarabia, Alfonso M, Ryan, Dermot, Bosnic-Anticevich, Sinthia, Valiulis, Arunas, Durham, Stephen L, Schünemann, Holger, Kalayci, Omer, Valovirta, Erkka, Panzner, Petr, Vandenplas, Olivier, Ventura, Maria Teresa, Gotua, Maia, Vichyanond, Pakit, Chkhartishvili, Ekaterine, Wagenmann, Martin, Fontaine, Jean-François, Kull, Inger, Wallace, Dana, Recto, Marysia, Walusiak-Skorupa, Jolanta, Wang, De Yun, Hrubiško, Martin, Waserman, Susan, Ebisawa, Motohiro, Bosse, Isabelle, Grisle, Ineta, Wong, Gary Wk, Bindslev-Jensen, Carsten, Yorgancioglu, Arzu, Yusuf, Osman M, Khaitov, Musa, Zernotti, Mario, Gawlik, Radoslaw, Chu, Derek K, Irani, Carla, Zhang, Luo, Zidarn, Mihaela, Zuberbier, Torsten, Kuna, Piotr, Jutel, Marek, Guzmán, Maria Antonieta, El-Gamal, Yehia, Klimek, Ludger, Brough, Helen A, Brussino, Luisa, Calderon, Moises A, Caraballo, Luis, O'Hehir, Robyn E, Gelincik, Asli, Kvedariene, Violeta, Cirule, Ieva, Cruz, Alvaro A, Czarlewski, Wienczyslawa, Nekam, Kristof, Papadopoulos, Nikolaos G., Haahtela, Tari, Emuzyte, Regina, Gamkrelidze, Amiran, Fauquert, Jean Luc, Palomares, Oscar, Regateiro, Frederico S, Ivancevich, Juan Carlos, Gemicioglu, Bilun, Gereda, Jose E, Gerth van Wijk, Roy, Bergmann, Karl-Christian, Knol, Edward, Halken, Susanne, Heffler, Enrico, Hoffmann-Sommergruber, Karin, Martins, Pedro Carreiro, Kritikos, Vicky, Ispayeva, Zhanat, Julge, Kaja, Kaidashev, Igor, Demoly, Pascal, Kowalski, Marek, Kraxner, Helga, Ollert, Markus, Fiocchi, Alessandro, Lauerma, Antti, Lau, Susanne, Park, Hae-Sim, Gomez, R Maximiliano, Comprehensive Health Research Centre (CHRC) - pólo NMS, Centro de Estudos de Doenças Crónicas (CEDOC), NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM), uBibliorum, Bousquet J., Pfaar O., Agache I., Bedbrook A., Akdis C.A., Canonica G.W., Chivato T., Al-Ahmad M., Abdul Latiff A.H., Ansotegui I.J., Bachert C., Baharuddin A., Bergmann K.-C., Bindslev-Jensen C., Bjermer L., Bonini M., Bosnic-Anticevich S., Bosse I., Brough H.A., Brussino L., Calderon M.A., Caraballo L., Cardona V., Carreiro-Martins P., Casale T., Cecchi L., Cepeda Sarabia A.M., Chkhartishvili E., Chu D.K., Cirule I., Cruz A.A., Czarlewski W., del Giacco S., Demoly P., Devillier P., Dokic D., Durham S.L., Ebisawa M., El-Gamal✝ Y., Emuzyte R., Gamkrelidze A., Fauquert J.L., Fiocchi A., Fokkens W.J., Fonseca J.A., Fontaine J.-F., Gawlik R., Gelincik A., Gemicioglu B., Gereda J.E., Gerth van Wijk R., Gomez R.M., Gotua M., Grisle I., Guzman M.-A., Haahtela T., Halken S., Heffler E., Hoffmann-Sommergruber K., Hossny E., Hrubisko M., Irani C., Ivancevich J.C., Ispayeva Z., Julge K., Kaidashev I., Kalayci O., Khaitov M., Klimek L., Knol E., Kowalski M.L., Kraxner H., Kull I., Kuna P., Kvedariene V., Kritikos V., Lauerma A., Lau S., Laune D., Levin M., Larenas-Linnemann D.E., Lodrup Carlsen K.C., Lombardi C., Lourenco O.M., Mahboub B., Malling H.-J., Manning P., Marshall G.D., Melen E., Meltzer E.O., Miculinic N., Milenkovic B., Moin M., Montefort S., Morais-Almeida M., Mortz C.G., Mosges R., Mullol J., Namazova Baranova L., Neffen H., Nekam K., Niedoszytko M., Odemyr M., O'Hehir R.E., Ollert M., O'Mahony L., Ohta K., Okamoto Y., Okubo K., Pajno G.B., Palomares O., Palkonen S., Panzner P., G Papadopoulos N., Park H.-S., Passalacqua G., Patella V., Pawankar R., Pham-Thi N., Plavec D., Popov T.A., Recto M., Regateiro F.S., Riggioni C., Roberts G., Rodriguez-Gonzales M., Rosario N., Rottem M., Rouadi P.W., Ryan D., Samolinski B., Sanchez-Borges✝ M., Serpa F.S., Sastre J., Scadding G.K., Shamji M.H., Schmid-Grendelmeier P., Schunemann H.J., Sheikh A., Scichilone N., Sisul J.C., Sofiev M., Sole D., Sooronbaev T., Soto-Martinez M., Soto-Quiros M., Sova M., Schwarze J., Skypala I., Suppli-Ulrik C., Taborda-Barata L., Todo-Bom A., Torres M.J., Valentin-Rostan M., Tomazic P.-V., Valero A., Toppila-Salmi S., Tsiligianni I., Untersmayr E., Urrutia-Pereira M., Valiulis A., Valovirta E., Vandenplas O., Ventura M.T., Vichyanond P., Wagenmann M., Wallace D., Walusiak-Skorupa J., Wang D.Y., Waserman S., Wong G.W.K., Yorgancioglu A., Yusuf O.M., Zernotti M., Zhang L., Zidarn M., Zuberbier T., Jutel M., HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, University of Helsinki, Department of Pathology, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Philipps Universität Marburg = Philipps University of Marburg, Transilvania University of Brasov, Universität Zürich [Zürich] = University of Zurich (UZH), Humanitas University [Milan] (Hunimed), Universidad San Pablo CEU, Kuwait University, Al-Rashed Allergy Center [Kuwait City], Pantai Hospital [Kuala Lumpur], Hospital Quirónsalud Bizkaia [Bilbao], Ghent University Hospital, Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], Sun Yat-Sen University [Guangzhou] (SYSU), Universiti Sains Malaysia (USM), Humboldt University Of Berlin, Berlin Institute of Health (BIH), Odense University Hospital (OUH), Skane University Hospital [Lund], Fondazione Policlinico Universitario Agostino Gemelli IRCCS, National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Woolcock Institute of Medical Research [Sydney], The University of Sydney, Guy's and St Thomas' Hospital [London], King‘s College London, Università degli studi di Torino = University of Turin (UNITO), University of Cartagena, Vall d'Hebron University Hospital [Barcelona], Centro Hospitalar de Lisboa Central E.P.E, NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), University of South Florida [Tampa] (USF), Azienda Usl Toscana centro [Firenze], Universidad Simon Bolivar (USB), David Tvildiani Medical University (DTMU), McMaster University [Hamilton, Ontario], Children's Clinical University Hospital [Riga, Latvia] (CCUH), Universidade Federal da Bahia (UFBA), Università degli Studi di Cagliari = University of Cagliari (UniCa), Epidemiology of Allergic and Respiratory Diseases Department [iPlesp] (EPAR), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Foch [Suresnes], Sagamihara National Hospital [Kanagawa, Japan], Université Ain Shams, Vilnius University [Vilnius], CHU Clermont-Ferrand, IRCCS Ospedale Pediatrico Bambino Gesù [Roma], Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA), Universidade do Porto = University of Porto, Silesian Medical University, Katowice, Poland, Cerrahpasa Faculty of Medicine, Istanbul University, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Universidad de Chile = University of Chile [Santiago] (UCHILE), Humanitas Clinical and Research Center [Rozzano, Milan, Italy], Medizinische Universität Wien = Medical University of Vienna, Hôtel-Dieu de France (HDF), Université Saint-Joseph de Beyrouth (USJ), Tartu University Hospital [Tartu, Estonia], Ukrainina Medical Stomatological Academy [Poltava, Ukraine], Hacettepe University = Hacettepe Üniversitesi, Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Siriraj Hospital, Mahidol University, Mahidol University [Bangkok], Nova Southeastern University (NSU), Nofer Institute of Occupational Medicine (NIOM), National University of Singapore (NUS), Yong Loo Lin School of Medicine [Singapore], The Chinese University of Hong Kong [Hong Kong], Manisa Celal Bayar University, Universidad Nacional de Villa María, Universidad Católica de Córdoba, Beijing Tongren Hospital, Herrada, Anthony, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, and UCL - (MGD) Service de pneumologie
Subjects: Pulmonary and Respiratory Medicine, precision medicine, education, Immunology, Review, Settore MED/10 - Malattie Dell'Apparato Respiratorio, immune system diseases, HDE ALER, allergic rhinitis, asthma, immunotherapy, Medicine and Health Sciences, Immunology and Allergy, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, ComputingMilieux_MISCELLANEOUS, Rhinitis, RC581-607, respiratory tract diseases, 3121 General medicine, internal medicine and other clinical medicine, Immunologic diseases. Allergy, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology, allergic rhinitis, asthma, immunotherapy, precision medicine
Abstract: Funding Information: BSreports personal fees from Allergopharma, during the conduct of the study; grants from National Health Programm, grant, personal fees from Polpharma, ASTRA, personal fees from Mylan, Adamed, patient ombudsman, national Centre for Research and Development, Polish Allergology Society. Funding Information: NGP reports personal fees from Novartis, Nutricia, HAL, MENARINI/FAES FARMA, SANOFI, MYLAN/MEDA, BIOMAY, AstraZeneca, GSK, MSD, ASIT BIOTECH, Boehringer Ingelheim, grants from Gerolymatos International SA, Capricare. Funding Information: CA reports grants from Allergopharma, grants from Idorsia, Swiss National Science Foundation, Christine Kühne‐Center for Allergy Research and Education, European Commission's Horison's 2020 Framework Programme, Cure, Novartis Research Institutes, Astra Zeneca, scibase, advisory role in Sanofi/Regeneron, grants from Glakso Smith‐Kline, advisory role in scibase. Funding Information: MJTreports grants from European Commission, SEAIC, ISCIII, personal fees from Diater laboratory, Leti laboratory, Aimmune Therapeutics. Funding Information: LK reports grants and personal fees from Allergopharma, MEDA/Mylan, LETI Pharma, Sanofi, grants from Stallergenes, Quintiles, ASIT biotech, grants from ALK Abelló, Lofarma, AstraZeneca, GSK, Inmunotk, personal fees from Allergy Therapeut., HAL Allergie, Cassella med; and Membership: AeDA, DGHNO, Deutsche Akademie für Allergologie und klinische Immunologie, HNO‐BV, GPA, EAACI. Funding Information: DPreports grants and personal fees from GlaxoSmithKline, personal fees from Menarini, Pliva, Belupo, AbbVie, Novartis, MSD, Chiesi, Revenio, personal fees and non‐financial support from Boehringer Ingelheim, non‐financial support from Philips. Funding Information: OP reports grants and personal fees from ALK‐Abelló, Allergopharma, Stallergenes Greer, HAL Allergy Holding B.V./HAL Allergie GmbH, Bencard Allergie GmbH/Allergy Therapeutics, Lofarma, ASIT Biotech Tools S.A., Laboratorios LETI/LETI Pharma, Anergis S.A., Glaxo Smith Kline, grants from Biomay, Circassia, Pohl‐Boskamp, Inmunotek S.L., personal fees from MEDA Pharma/MYLAN, Mobile Chamber Experts (a GA2LEN Partner), Indoor Biotechnologies, Astellas Pharma Global, EUFOREA, ROXALL Medizin, Novartis, Sanofi‐Aventis and Sanofi‐Genzyme, Med Update Europe GmbH, streamedup! GmbH, John Wiley and Sons, AS. Copyright: Copyright 2021 Elsevier B.V., All rights reserved. publishersversion published
Published: 2021

21. Management of congenital ichthyoses

Author: Khaled Ezzedine, Emmanuelle Bourrat, Anette Bygum, Anders Vahlquist, Christine Bodemer, A. Pietrzak, Smail Hadj-Rabia, Judith Fischer, C. Gouveia, Andrea Diociaiuti, Hagen Ott, Juliette Mazereeuw-Hautier, D.G. Paige, A. Audouze, Robert Gruber, Michael C. Rodriguez, Heiko Traupe, Matthias Schmuth, C. Amaro, D. Maier, G. Wehr, Edel A. O'Toole, M. El Hachem, M. Moreen, J.C. Sitek, Daniel Hohl, Ángela Hernández‐Martín, Agneta Gånemo, Vinzenz Oji, Nathalie Jonca, Isabelle Dreyfus, Raman Malhotra, Mateja Dolenc-Voljč, M. Aldwin, P.M. Steijlen, F. Poot, MUMC+: MA Dermatologie (3), Dermatologie, MUMC+: MA AIOS Dermatologie (9), MUMC+: MA Dermatologie (9), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, CHU Toulouse [Toulouse], Hospital Infantil Universitario Niño Jesús (HIUNJ), Queen Mary University of London (QMUL), Bart's and The London School of Medicine and Dentistry, Odense University Hospital (OUH), Hospital de Santa Maria [Lisboa], Ichthyosis Support Group, PO Box 1242, Yateley, GU47 7FL, U.K., Association Ichtyose France, Bellerive sur Allier, France., Service de dermatologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bambino Gesù Children’s Hospital [Rome, Italy], University Medical Centre Ljubljana [Ljubljana, Slovenia] (UMCL), University of Freiburg [Freiburg], Skane University Hospital [Malmo], Lund University [Lund], Bern University Hospital [Berne] (Inselspital), University of Innsbruck, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Unité différenciation épidermique et auto-immunité rhumatoïde (UDEAR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Henri Mondor, Epidemiology in Dermatology and Evaluation in Therapeutics (EpiDermE), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Iuliu Hatieganu University of Medicine & Pharmacy, Queen Victoria Hospital NHS Foundation Trust, Hospital Universitario Son Espases, Children's Hospital 'Auf der Bult', Royal Free Hospital [London, UK], Medical University of Lublin, Oslo University Hospital [Oslo], Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], University Hospitals Leuven [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Uppsala University, and University Hospital Münster - Universitaetsklinikum Muenster [Germany] (UKM)
Subjects: VITAMIN-D DEFICIENCY, medicine.medical_specialty, Consensus, MESH: Dermatology / methods, [SDV]Life Sciences [q-bio], ORAL RETINOID THERAPY, MEDLINE, Dermatology, Infant, Premature, Diseases, MESH: Ichthyosis / therapy, Double blind, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Quality of life (healthcare), Premature epiphyseal closure, Multidisciplinary approach, Congenital ichthyosis, medicine, Humans, MESH: Consensus, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, MESH: Infant, Premature, Diseases / therapy, MESH: Ichthyosiform Erythroderma, Congenital / complications, MESH: Ichthyosis / complications, MESH: Humans, business.industry, X-LINKED ICHTHYOSIS, Ichthyosis, Lamellar ichthyosis, Ichthyosiform Erythroderma, Congenital, medicine.disease, TRICHOPHYTON-RUBRUM INFECTION, DEAFNESS KID SYNDROME, MESH: Dermatology / standards, Europe, HARLEQUIN ICHTHYOSIS, NETHERTON-SYNDROME, Family medicine, MESH: Ichthyosiform Erythroderma, Congenital / therapy, CICATRICIAL ECTROPION, 030221 ophthalmology & optometry, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Europe, SQUAMOUS-CELL CARCINOMA, business, CHRONIC PAIN MANAGEMENT, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, Kid syndrome
Abstract: These guidelines for the management of congenital ichthyoses have been developed by a multidisciplinary group of European experts following a systematic review of the current literature, an expert conference held in Toulouse in 2016, and a consensus on the discussions. These guidelines summarize evidence and expert-based recommendations and intend to help clinicians with the management of these rare and often complex diseases. These guidelines comprise two sections. This is part two, covering the management of complications and the particularities of some forms of congenital ichthyosis.What's already known about this topic?Various symptomatic treatment options exist for congenital ichthyoses, but there are no European guidelines.What does this study add?These European guidelines for the management of congenital ichthyosis may help to improve outcomes and quality of life for patients.Linked Comment: Akiyama. Br J Dermatol 2019; 180:449-450. Plain language summary available online
Published: 2019

22. Management of congenital ichthyoses

Author: J. Mazereeuw‐Hautier, A. Vahlquist, H. Traupe, A. Bygum, C. Amaro, M. Aldwin, A. Audouze, C. Bodemer, E. Bourrat, A. Diociaiuti, M. Dolenc‐Voljc, I. Dreyfus, M. El Hachem, J. Fischer, A. Gånemo, C. Gouveia, R. Gruber, S. Hadj‐Rabia, D. Hohl, N. Jonca, K. Ezzedine, D. Maier, R. Malhotra, M. Rodriguez, H. Ott, D.G. Paige, A. Pietrzak, F. Poot, M. Schmuth, J.C. Sitek, P. Steijlen, G. Wehr, M. Moreen, E.A. O'Toole, V. Oji, A. Hernandez‐Martin, MUMC+: MA Dermatologie (3), Dermatologie, MUMC+: MA AIOS Dermatologie (9), MUMC+: MA Dermatologie (9), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, CHU Toulouse [Toulouse], Uppsala University, Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Odense University Hospital (OUH), Hospital de Santa Maria [Lisboa], Ichthyosis Support Group, PO Box 1242, Yateley, GU47 7FL, U.K., Association Ichtyose France, Bellerive sur Allier, France., CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hopital Saint-Louis [AP-HP] (AP-HP), Bambino Gesù Children’s Hospital [Rome, Italy], University Medical Centre Ljubljana [Ljubljana, Slovenia] (UMCL), University of Freiburg [Freiburg], Skane University Hospital [Malmo], Lund University [Lund], Bern University Hospital [Berne] (Inselspital), University of Innsbruck, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Unité différenciation épidermique et auto-immunité rhumatoïde (UDEAR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Epidemiology in Dermatology and Evaluation in Therapeutics (EpiDermE), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Iuliu Hatieganu University of Medicine & Pharmacy, Queen Victoria Hospital NHS Foundation Trust, Hospital Universitario Son Espases, Children's Hospital 'Auf der Bult', Royal Free Hospital [London, UK], Medical University of Lublin, Oslo University Hospital [Oslo], Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], University Hospitals Leuven [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Queen Mary University of London (QMUL), University Hospital Münster - Universitaetsklinikum Muenster [Germany] (UKM), and Hospital Infantil Universitario Niño Jesús (HIUNJ)
Subjects: VITAMIN-D DEFICIENCY, PREMATURE EPIPHYSEAL CLOSURE, Consensus, MESH: Dermatology / methods, Administration, Topical, MESH: Social Support, ORAL RETINOID THERAPY, Administration, Oral, Genetic Counseling, Dermatology, MESH: Ichthyosiform Erythroderma, Congenital / psychology, 030207 dermatology & venereal diseases, 03 medical and health sciences, DOUBLE-BLIND, BONE CHANGES, 0302 clinical medicine, Behavior Therapy, QUALITY-OF-LIFE, MESH: Dermatologic Agents / therapeutic use, EPIDERMOLYTIC HYPERKERATOSIS, Humans, MESH: Consensus, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, KID SYNDROME, MESH: Humans, MESH: Behavior Therapy / standards, MESH: Behavior Therapy / methods, MESH: Ichthyosiform Erythroderma, Congenital / diagnosis, Social Support, MESH: Quality of Life, Ichthyosiform Erythroderma, Congenital, MESH: Dermatology / standards, MESH: Administration, Topical, Europe, HARLEQUIN ICHTHYOSIS, MESH: Genetic Counseling / standards, MESH: Ichthyosiform Erythroderma, Congenital / therapy, MESH: Administration, Oral, Quality of Life, [SDV.IMM]Life Sciences [q-bio]/Immunology, LAMELLAR ICHTHYOSIS, Dermatologic Agents, MESH: Europe, MESH: Systematic Reviews as Topic, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, Systematic Reviews as Topic
Abstract: International audience; These guidelines for the management of congenital ichthyoses have been developed by a multidisciplinary group of European experts following a systematic review of the current literature, an expert conference held in Toulouse in 2016 and a consensus on the discussions. They summarize evidence and expert-based recommendations and are intended to help clinicians with the management of these rare and often complex diseases. These guidelines comprise two sections. This is part one, covering topical therapies, systemic therapies, psychosocial management, communicating the diagnosis and genetic counselling.
Published: 2019

23. The PRISMA 2020 statement:An updated guideline for reporting systematic reviews

Author: Matthew J. Page, Elizabeth Loder, Cynthia D. Mulrow, Julie Glanville, Vivian Welch, James Thomas, Patrick M.M. Bossuyt, Larissa Shamseer, Jennifer Tetzlaff, Tammy Hoffmann, Jeremy M. Grimshaw, Isabelle Boutron, David Moher, Asbjørn Hróbjartsson, Manoj M. Lalu, Andrea C. Tricco, Evan Mayo-Wilson, Luke A McGuinness, Joanne E. McKenzie, Penny Whiting, Tianjing Li, Roger Chou, Steve McDonald, Sue E. Brennan, Elie A. Akl, Lesley A. Stewart, Université Paris Cité, Equipe HAL, Monash University [Melbourne], VU University Medical Center [Amsterdam], Equipe 5 : METHODS - Méthodes de l’évaluation thérapeutique des maladies chroniques (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), Bond University [Gold Coast], The University of Texas Health Science Center at Houston (UTHealth), University of Ottawa [Ottawa], Auteur indépendant, McMaster University [Hamilton, Ontario], Oregon Health and Science University [Portland] (OHSU), York Health Economics Consortium, University of York, Centre for Evidence-Based Medicine Odense (CEBMO), Odense University Hospital (OUH), Ottawa Hospital Research Institute [Ottawa] (OHRI), Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Harvard Medical School [Boston] (HMS), Indiana University [Bloomington], Indiana University System, University of Bristol [Bristol], University of York [York, UK], University College of London [London] (UCL), University of Toronto, Epidemiology and Data Science, APH - Methodology, APH - Personalized Medicine, and 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)
Subjects: Research Report, Epidemiology, Computer science, Statement (logic), [SDV]Life Sciences [q-bio], Statistics as Topic, lcsh:Medicine, Medicine (miscellaneous), 030204 cardiovascular system & hematology, Terminology, Guidelines and Guidance, Database and Informatics Methods, Mathematical and Statistical Techniques, 0302 clinical medicine, Medicine and Health Sciences, Medicine, 030212 general & internal medicine, Meta-Analysis as Topic, ComputingMilieux_MISCELLANEOUS, Research reporting guidelines, Evidence-Based Medicine, 030503 health policy & services, Statistics, Reporting guideline, bepress|Medicine and Health Sciences, General Medicine, Research Assessment, Metaanalysis, MetaArXiv|Medicine and Health Sciences, Reproducibility, Checklist, 3. Good health, [SDV] Life Sciences [q-bio], Systematic review, Research Design, Meta-analysis, 030220 oncology & carcinogenesis, Physical Sciences, Practice Guidelines as Topic, 030211 gastroenterology & hepatology, 0305 other medical science, Quality Control, medicine.medical_specialty, MEDLINE, Systematic review methodology, Guidelines as Topic, Health care policy reports, Research and Analysis Methods, Transparency, 03 medical and health sciences, Terminology as Topic, Humans, Medical physics, Statistical Methods, Health care providers, Publishing, Statement (computer science), Medical education, Health Care Policy, business.industry, Research, lcsh:R, Systematic reviews, Guideline, Medical Writing, Database searching, Health Care, Medical risk factors, Surgery, Research Report/standards, business, Mathematics, 030217 neurology & neurosurgery, Systematic Reviews as Topic
Abstract: Background: The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) Statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, what the authors did and what they found. Over the last decade, there have been many advances in systematic review methodology and terminology, which have necessitated an update to the guideline.Objectives: To develop the PRISMA 2020 statement for reporting systematic reviews.Methods: We reviewed 60 documents with reporting guidance for systematic reviews to generate suggested modifications to the PRISMA 2009 statement. We sought feedback on the suggested modifications through an online survey of 110 systematic review methodologists and journal editors. The results of the review and survey were discussed at a 21-member in-person meeting. Following the meeting, drafts of the PRISMA 2020 checklist, abstract checklist, explanation and elaboration and flow diagram were generated and refined iteratively based on feedback from co-authors and a convenience sample of 15 systematic reviewers.Results: In this statement paper, we present the PRISMA 2020 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and the revised flow diagrams for original and updated reviews. The checklist includes new reporting guidance that reflects advances in methods to identify, select, appraise and synthesise studies. The structure and presentation of the items have been modified to facilitate implementation. The PRISMA 2020 statement replaces the 2009 statement.Conclusions: The PRISMA 2020 statement is intended to facilitate transparent, complete and accurate reporting of systematic reviews. Improved reporting should benefit users of reviews, including guideline developers, policy makers, health care providers, patients and other stakeholders. In order to achieve this, we encourage authors, editors and peer-reviewers to adopt the guideline.
Published: 2021

24. Research response to coronavirus disease 2019 needed better coordination and collaboration: a living mapping of registered trials

Author: Nguyen, van Thu, Riviere, Philippe, Ripoll, Pierre, Barnier, Julien, Vuillemot, Romain, Ravaud, Philippe, Boutron, Isabelle, Nma Consortium, Covid, Alawadhi, Solaf, Amer-Yahia, Sihem, Ávila, Camila, Bafeta, Aïda, Baudry, Julia, Bollig, Claudia, Bonnet, Hillary, Bouet, Marinette, Cabanac, Guillaume, Chaimani, Anna, Chavalarias, David, Chen, Yaolong, Chevance, Astrid, Cohen-Boulakia, Sarah, Coquery, Emmanuel, Conil, Françoise, Davidson, Mauricia, de Nale, Laura, Devane, Declan, Diard, Elise, Doreau, Bastien, Evrenoglou, Theodoros, Fabri, Alice, Feron, Gilles, Ferrand, Gabriel, Fezeu, Leopold, Fouet, Mathilde, El Chall, Lina Ghosn, Graña, Carolina, Grasselli, Giacomo, Grolleau, François, Hacid, Mohand-Said, Haddy, Loubna, Hansen, Camilla, Hohlfeld, Ameer, Hróbjartsson, Asbjørn, Julia, Chantal, Mavridis, Dimitris, Meerpohl, Joerg, Meyer, Brice, Naidoo, Nivantha, Oikonomidi, Theodora, Pienaar, Elizabeth, Quirke, Fiona, Rada, Gabriel, Riveros, Carolina, Sauvant, Marie, Schmucker, Christine, Toumani, Farouk, Tovey, David, Xia, Jun, Yu, Xuan, Zoletic, Emina, Zweigenbaum, Pierre, 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), French Cochrane Centre, VisionsCarto, Laboratoire d'InfoRmatique en Image et Systèmes d'information (LIRIS), Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Centre Max Weber (CMW), École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), BioInformatique (BioInfo), Laboratoire Interdisciplinaire des Sciences du Numérique (LISN), Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Science des Données (SDD), Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Centre d'épidémiologie Clinique [Hôtel-Dieu], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Hôtel Dieu, COVID-NMA Consortium Team: Solaf Alawadhi , Sihem Amer-Yahia , Camila Ávila , Aïda Bafeta , Julia Baudry , Claudia Bollig , Hillary Bonnet , Isabelle Boutron , Marinette Bouet , Guillaume Cabanac , Anna Chaimani , David Chavalarias , Yaolong Chen , Astrid Chevance , Sarah Cohen-Boulakia , Emmanuel Coquery , Francoise Conil , Mauricia Davidson , Laura De Nale , Declan Devane , Elise Diard , Bastien Doreau , Theodoros Evrenoglou , Alice Fabri , Gilles Feron , Gabriel Ferrand , Leopold Fezeu , Mathilde Fouet , Lina Ghosn El Chall , Carolina Graña , Giacomo Grasselli , François Grolleau , Mohand-Said Hacid , Loubna Haddy , Camilla Hansen , Ameer Hohlfeld , Asbjørn Hróbjartsson , Chantal Julia , Dimitris Mavridis , Joerg J Meerpohl , Brice Meyer , Nivantha Naidoo , Van Nguyen Thu , Theodora Oikonomidi , Elizabeth Pienaar , Fiona Quirke , Gabriel Rada , Philippe Ravaud , Pierre Ripoll , Carolina Riveros , Philippe Rivière , Marie Sauvant , Christine Schmucker , Farouk Toumani , David Tovey , Romain Vuillemot , Jun Xia , Xuan Yu , Emina Zoletic , Pierre Zweigenbaum, ANR-20-COVI-0084,living-NMA-covid,Efficacités des interventions contre l'infection Covid-19 : une cartographie de la recherche dynamique et séries de méta-analyses en réseau dynamiques(2020), 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), Situated Interaction, Collaboration, Adaptation and Learning (SICAL), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École Centrale de Lyon (ECL), Université de Lyon-Université Lumière - Lyon 2 (UL2)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Université Lumière - Lyon 2 (UL2), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Monnet [Saint-Étienne] (UJM), Equipe 5 : METHODS - Méthodes de l’évaluation thérapeutique des maladies chroniques (CRESS - U1153), 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), Laboratoire d'Informatique de Grenoble (LIG), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Epistemonikos Foundation, Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Sorbonne Paris Nord-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), German Cochrane Centre, University Medical Centre Freiburg, LEB Aquitaine Transfert-ADERA, Laboratoire d'Informatique, de Modélisation et d'Optimisation des Systèmes (LIMOS), Ecole Nationale Supérieure des Mines de St Etienne-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Recherche d’Information et Synthèse d’Information (IRIT-IRIS), Institut de recherche en informatique de Toulouse (IRIT), Université Toulouse 1 Capitole (UT1), 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-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées, Université Toulouse III - Paul Sabatier (UT3), Institut des Systèmes Complexes - Paris Ile-de-France (ISC-PIF), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Sorbonne Université (SU)-École polytechnique (X)-École normale supérieure - Cachan (ENS Cachan)-Université Paris 1 Panthéon-Sorbonne (UP1), Lanzhou University, CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Science des Données (SDD), CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Evidence Synthesis Ireland, Cochrane Ireland, Centre for Evidence-Based Medicine Odense (CEBMO), Odense University Hospital (OUH), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital d'instruction des Armées Percy, Service de Santé des Armées, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, SANOFI Recherche, COCHRANE SOUTH AFRICA, University of Ioannina, Freiburg University Medical Center, HRB Trials Methodology Research Network (HRB-TRMN), Cochrane Chile, University of Nottingham Ningbo [China], Information, Langue Ecrite et Signée (ILES), Laboratoire d'Informatique pour la Mécanique et les Sciences de l'Ingénieur (LIMSI), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS), 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), École normale supérieure - Cachan (ENS Cachan)-Université Paris 1 Panthéon-Sorbonne (UP1)-École polytechnique (X)-Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Base de Données (BD), Universitäts Klinikum Freiburg = University Medical Center Freiburg (Uniklinik), CCSD, Accord Elsevier, and École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV] Life Sciences [q-bio], Clinical trial, Living mapping, Treatment, Meta-analysis, Prevention, [SDV]Life Sciences [q-bio], Systematic review, COVID-19
Abstract: International audience; BackgroundResearchers worldwide are actively engaging in research activities to search for preventive and therapeutic interventions against COVID-19. Our aim was to describe the planning of randomized controlled trials (RCTs) in terms of timing related to the course of the COVID-19 epidemic and research question evaluated.MethodWe performed a living mapping of RCTs registered in the WHO International Clinical Trials Registry Platform. We systematically search the platform every week for all RCTs evaluating preventive interventions and treatments for COVID-19 and created a publicly available interactive mapping tool at https://covid-nma.com to visualize all trials registered.ResultsBy August 12, 2020, 1,568 trials for COVID-19 were registered worldwide. Overall, the median ([Q1-Q3]; range) delay between the first case recorded in each country and the first RCT registered was 47 days ([33-67]; 15-163). For the 9 countries with the highest number of trials registered, most trials were registered after the peak of the epidemic (from 100% trials in Italy to 38% in the United States). Most trials evaluated treatments (1,333 trials; 85%); only 223 (14%) evaluated preventive strategies and 12 post-acute period intervention. A total of 254 trials were planned to assess different regimens of hydroxychloroquine with an expected sample size of 110,883 patients.ConclusionThis living mapping analysis showed that COVID-19 trials have relatively small sample size with certain redundancy in research questions. Most trials were registered when the first peak of the pandemic have passed.
Published: 2021

25. Influence and management of conflicts of interest in randomised clinical trials : qualitative interview study

Author: Mustafe Hassan Adan Gelle, Lesley A. Stewart, Lasse Østengaard, Andreas Lundh, Isabelle Boutron, Tine Tjørnhøj-Thomsen, Asbjørn Hróbjartsson, Suhayb Ahmed Ibrahim Sheekh Abdi, Centre for Evidence-Based Medicine Odense (CEBMO), Odense University Hospital (OUH), Open Patient data Exploratory Network (OPEN), Department of Clinical Research, University of Southern Denmark (SDU), University Library of Southern Denmark, Department of Infectious Diseases, Hvidovre Hospital, National Institute of Public Health, Centre for Reviews and Dissemination, University of York [York, UK], 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), 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), and Lallemant, Christopher
Subjects: Male, [SDV]Life Sciences [q-bio], MEDLINE, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Political agenda, Humans, 030212 general & internal medicine, Location, Qualitative Research, Randomized Controlled Trials as Topic, Medical education, Conflict of Interest, Qualitative interviews, Research, Conflict of interest, General Medicine, Research Personnel, Antiinflammatory Drugs Bias Guidelines Risk, [SDV] Life Sciences [q-bio], Clinical trial, Snowball sampling, Female, Psychology, Qualitative research
Abstract: Objective To characterise and analyse the experiences of trial researchers of if and how conflicts of interest had unduly influenced clinical trials they had worked on, what management strategies they had used to minimise any potential influence, and their experiences and views on conflicts of interest more generally. Design Qualitative interview study. Participants Trial researchers who had participated in at least 10 clinical trials with methodological or statistical expertise. Researchers differed by geographical location, educational background, and experience with different types of funders. Interviewees were identified by searches on Web of Science and snowball sampling. 52 trial researchers were approached by email; 20 agreed to be interviewed. Setting Interviews conducted by telephone, recorded, transcribed verbatim, imported to NVivo 12, and analysed by systematic text condensation. Semistructured interviews focused on financial and non-financial conflicts of interest. Results The interviewees had participated in a median of 37.5 trials and were mainly male physicians who had experience with commercial and non-commercial trial funders. Two predefined themes (influence of conflicts of interest and management strategies) and two additional themes (definition and reporting of conflicts of interest) emerged. Examples of perceived influence of conflicts of interest were: choice of inferior comparator, manipulation of the randomisation process, prematurely stopping the trials, fabrication of data, blocking access to data, and spin (eg, overly favourable interpretation of the results). Examples of strategies to manage conflicts of interest were: disclosure procedures, exclusion of the funder from design and analysis, independent committees, contracts ensuring complete access to the data, and no restriction by the funder on analysis and reporting. Interviewees used different definitions or thresholds for what they considered to be conflicts of interest, and they described different criteria for when to report them. Some interviewees considered non-commercial financial conflicts of interest (eg, funding of trials by governmental health agencies with a political agenda) to be equally or more important than commercial financial conflicts of interest (eg, funding by drug and device companies), but more challenging to report and manage. Conclusion This study described how trial researchers perceive conflicts of interest unduly influencing clinical trials they had worked on, and the management strategies they used to prevent these influences. The results indicated considerable variability in researchers’ understanding of what conflicts of interest are and when they should be reported.
Published: 2020

26. Reporting of harms in oncological clinical study reports submitted to the European Medicines Agency compared to trial registries and publications-a methodological review

Author: Isabelle Boutron, Perrine Crequit, Asger Sand Paludan-Müller, Malbec, Odile, University of Southern Denmark (SDU), Odense University Hospital (OUH), Hôpital Foch [Suresnes], 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), French Cochrane Centre, Hôtel-Dieu, and 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)
Subjects: Research Report, medicine.medical_specialty, [SDV]Life Sciences [q-bio], lcsh:Medicine, Medical Oncology, Clinical study, 03 medical and health sciences, 0302 clinical medicine, Clinical study reports, Agency (sociology), medicine, Humans, 030212 general & internal medicine, Registries, Adverse effect, business.industry, Harms, lcsh:R, General Medicine, Systematic reviews, 3. Good health, Clinical trial, [SDV] Life Sciences [q-bio], Systematic review, Reporting bias, 030220 oncology & carcinogenesis, Family medicine, Adverse events, Treatment decision making, business, Research Article
Abstract: Background An accurate and comprehensive assessment of harms is a fundamental part of an accurate weighing of benefits and harms of an intervention when making treatment decisions; however, harms are known to be underreported in journal publications. Therefore, we sought to compare the completeness of reporting of harm data, discrepancies in harm data reported, and the delay to access results of oncological clinical trials between three sources: clinical study reports (CSRs), clinical trial registries and journal publications. Methods We used the EMA clinical data website to identify all trials submitted to the EMA between 2015 and 2018. We retrieved all CSRs and included all phase II, II/III or III randomised controlled trials (RCTs) assessing targeted therapy and immunotherapy for cancer. We then identified related records in clinical trial registries and journals. We extracted harms data for eight pre-specified variables and determined the completeness of reporting of harm data in each of the three sources. Results We identified 42 RCTs evaluating 13 different drugs. Results were available on the EMA website in CSRs for 37 (88%) RCTs, ClinicalTrials.gov for 36 (86%), the European Clinical Trials Register (EUCTR) for 20 (48%) and in journal publications for 32 (76%). Harms reporting was more complete in CSRs than other sources. We identified marked discrepancies in harms data between sources, e.g. the number of patients discontinuing due to adverse events differed in CSRs and clinical trial registers for 88% of trials with data in both sources. For CSRs and publications, the corresponding number was 90%. The median (interquartile range) delay between the primary trial completion date and access to results was 4.34 (3.09–7.22) years for CSRs, 2.94 (1.16–4.52) years for ClinicalTrials.gov, 5.39 (4.18–7.33) years for EUCTR and 2.15 (0.64–5.04) years for publications. Conclusions Harms of recently approved oncological drugs were reported more frequently and in more detail in CSRs than in trial registries and journal publications. Systematic reviews seeking to address harms of oncological treatments should ideally use CSRs as the primary source of data; however, due to problems with access, this is currently not feasible.
Published: 2020

27. Allergen Immunotherapy (AIT) in children: a vulnerable population with its own rights and legislation – summary of EMA-initiated multi-stakeholder meeting on Allergen Immunotherapy (AIT) for children, held at Paul-Ehrlich-Institut, Langen, Germany, 16.1.2019

Author: Andreas Bonertz, S. Vieths, Jean Bousquet, Vera Mahler, Philippe Eigenmann, S. Kaul, Oliver Pfaar, Ulrich Wahn, D. Mentzer, Antonella Muraro, Marek Jutel, Susanne Halken, Paul-Ehrlich-Institute - Federal Institute for Vaccines and Biomedicines (EPI), Azienda Ospedale Università di Padova = Hospital-University of Padua (AOUP), Hôpitaux Universitaires de Genève (HUG), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], University of Southern Denmark (SDU), Odense University Hospital (OUH), Philipps Universität Marburg = Philipps University of Marburg, University of Wrocław [Poland] (UWr), and Retiveau, Nolwenn
Subjects: Pulmonary and Respiratory Medicine, Allergen immunotherapy, Allergy, medicine.medical_specialty, Paediatric Committee (PDCO), Therapy Allergen Ordinance (TAO), Immunology, Legislation, Review, Disease, Paediatric Investigation Plan (PIP), 030207 dermatology & venereal diseases, 03 medical and health sciences, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, 0302 clinical medicine, Agency (sociology), medicine, Immunology and Allergy, Vulnerable population, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, Children, Asthma, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, business.industry, European Medicines Agency (EMA), [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, RC581-607, Allergie, Allergen Immunotherapy (AIT), medicine.disease, Incentive, 030228 respiratory system, Family medicine, Immunologic diseases. Allergy, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, business, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology
Abstract: International audience; Concerning development of medicinal products, children belong to a so-called "special population" for which additional legislation applies: Regulation (EC) No 1901/2006 on medicinal products for paediatric use sets up a system of requirements, rewards and incentives to ensure that medicinal products are researched, developed and authorized to meet the therapeutic needs of children. Allergen Immunotherapy (AIT) is believed to contain a strong potential for immunomodulatory effects inducing sustained clinical efficacy after cessation of treatment (disease modifying effect) and thereby may prevent the progression of the atopic march towards asthma manifestation. However, to this day only few data on long-term effects in general exist and even fewer in children. These are predominantly data from open studies, which are strongly influenced in their validity by the known placebo effect of AIT. Furthermore, there are no studies allowing for the conclusion that efficacy in adults are mirrored by a similar efficacy in children and thus, up to now, it is not possible to extrapolate data from adults to children. The Paediatric Committee (PDCO)-European Medicines Agency's (EMA) scientific committee responsible for activities on medicines for children-initiated a Multi-Stakeholder Meeting on AIT for Children held at the Paul-Ehrlich-Institut in Langen, Germany, to provide a platform for discussion and exchange of thoughts to this topic between allergy experts from academia, regulators and AIT-manufacturers. The consented meeting minutes, conclusions and participants are presented.
Published: 2020

28. Systematic review finds that appraisal tools for medical research studies address conflicts of interest superficially

Author: Kristine Rasmussen, Lesley A. Stewart, Asbjørn Hróbjartsson, Lasse Østengaard, Andreas Lundh, Isabelle Boutron, Centre for Evidence-Based Medicine Odense (CEBMO), Odense University Hospital (OUH), Open Patient data Exploratory Network (OPEN), Department of Clinical Research, University of Southern Denmark (SDU), Department of Infectious Diseases, Hvidovre Hospital, Cochrane Nordic, Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, University Library of Southern Denmark, 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), Centre for Reviews and Dissemination, and University of York [York, UK]
Subjects: Biomedical Research, Conflict of Interest, Epidemiology, business.industry, Industry funding, Critical appraisal tools, Medical journals, Public relations, Medical research, 03 medical and health sciences, 0302 clinical medicine, Political science, Systematic review, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 030212 general & internal medicine, Conflicts of interest, Journal policies, business, Editorial Policies, 030217 neurology & neurosurgery
Abstract: ObjectivesThe objective of this study was to identify and summarize 1) appraisal tools and other guides which address conflicts of interest in medical research studies; and 2) top journals with policies on managing conflicts of interest in journal papers.Study Design and SettingWe searched bibliographic databases, other sources, and websites of 30 top medical journals. Two authors selected documents and extracted data.ResultsWe included 27 appraisal tools. None were designed specifically for addressing conflicts of interest and they included only 1-2 short items on conflicts of interest. We also included eight other types of guides. Of 27 appraisal tools, 23 addressed study funding, and 19 authors’ conflicts of interest. Nine tools addressed availability of conflicts of interest information, 13 reported conflicts of interest, and five influence from conflicts of interest. Twelve of 30 top journals had conflicts of interest managing policies (beyond disclosure). One journal restricted nonresearch papers (e.g., editorials) to authors without financial conflicts of interest and ten only restricted under certain circumstances.ConclusionAppraisal tools that address conflicts of interest typically do so superficially and rarely address how conflicts of interest may influence studies. Less than half of top medical journals have explicit policies on managing conflicts of interest. ObjectivesThe objective of this study was to identify and summarize 1) appraisal tools and other guides which address conflicts of interest in medical research studies; and 2) top journals with policies on managing conflicts of interest in journal papers.Study Design and SettingWe searched bibliographic databases, other sources, and websites of 30 top medical journals. Two authors selected documents and extracted data.ResultsWe included 27 appraisal tools. None were designed specifically for addressing conflicts of interest and they included only 1-2 short items on conflicts of interest. We also included eight other types of guides. Of 27 appraisal tools, 23 addressed study funding, and 19 authors’ conflicts of interest. Nine tools addressed availability of conflicts of interest information, 13 reported conflicts of interest, and five influence from conflicts of interest. Twelve of 30 top journals had conflicts of interest managing policies (beyond disclosure). One journal restricted nonresearch papers (e.g., editorials) to authors without financial conflicts of interest and ten only restricted under certain circumstances.ConclusionAppraisal tools that address conflicts of interest typically do so superficially and rarely address how conflicts of interest may influence studies. Less than half of top medical journals have explicit policies on managing conflicts of interest.
Published: 2020

29. European interdisciplinary guideline on invasive squamous cell carcinoma of the skin: Part 2. Treatment

Author: Stratigos, Alexander J, Garbe, Claus, Dessinioti, Clio, Lebbe, Celeste, Bataille, Veronique, Bastholt, Lars, Dreno, Brigitte, Concetta Fargnoli, Maria, Forsea, Ana M, Frenard, Cecille, Harwood, Catherine A, Hauschild, Axel, Hoeller, Christoph, Kandolf-Sekulovic, Lidija, Kaufmann, Roland, Kelleners-Smeets, Nicole W J, Malvehy, Josep, Del Marmol, Veronique, Middleton, Mark R, Moreno-Ramirez, David, Pellecani, Giovanni, Peris, Ketty, Saiag, Philippe, van den Beuken-van Everdingen, Marieke H J, Vieira, Ricardo, Zalaudek, Iris, Eggermont, Alexander M M, Grob, Jean-Jacques, European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organization for Research and Treatment of Cancer (EORTC), HAL UVSQ, Équipe, National and Kapodistrian University of Athens (NKUA), Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), North & East Hertfordshire NHS Trust [Northwood, UK], Odense University Hospital (OUH), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), University of L'Aquila [Italy] (UNIVAQ), University of Bucharest (UniBuc), Queen Mary University of London (QMUL), Kiel University, Medizinische Universität Wien = Medical University of Vienna, Military Medical Academy [Belgrade, Serbia] (2MA), Frankfurt University Hospital, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), CIBER de Enfermedades Raras (CIBERER), Université libre de Bruxelles (ULB), University of Oxford, Hospital Universitario Virgen Macarena [Sevilla, Spain] (HUVM), Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, Hôpital Ambroise Paré [AP-HP], Coimbra Hospital and Universitary Centre [Coimbra, Portugal] (CHUC), Università degli studi di Trieste = University of Trieste, Princess Máxima Center for Pediatric Oncology, Aix Marseille Université (AMU), Assistance Publique - Hôpitaux de Marseille (APHM), Amgen Bristol-Myers Squibb, BMS Pfizer AstraZeneca GlaxoSmithKline, GSK Merck Novartis Roche Sanofi AbbVie Meso Scale Diagnostics, MSD Merck Sharp and Dohme, MSD DUSA Pharmaceuticals Les Laboratories Pierre Fabre Cilag LEO Pharma Research Foundation, The development of the current set of guideline was supported solely by funds of the EADO which were used to mainly support the consensus meeting.Dr. Stratigos reports personal fees and/or research support from Novartis, Roche, BMS, AbbVie, Sanofi, Regeneron, Genesis Pharma, outside the submitted work. Dr. Garbe reports personal fees from Amgen, personal fees from MSD, grants and personal fees from Novartis, grants and personal fees from NeraCare, grants and personal fees from BMS, personal fees from Pierre Fabre, personal fees from Philogen, grants and personal fees from Roche, grants and personal fees from Sanofi, outside the submitted work. Dr. Dessinioti has nothing to disclose. Dr. Lebbe reports grants and personal fees from Bristol-Myers Squibb, personal fees from MSD, personal fees from Novartis, personal fees from Amgen, grants and personal fees from Roche, personal fees from Avantis Medical Systems, personal fees from Pierre Fabre, personal fees from Pfizer, personal fees from Incyte, outside the submitted work. Dr. Bataille reports personal fees from Novartis, personal fees from Merck MSD, outside the submitted work. Dr. Bastholt reports personal fees for advisory board activity: BMS, Roche, Novartis, Pierre Fabre, AstraZeneca, Incyte, MSD/Merck, Bayer. Dr. Dr?no reports grants and personal fees from BMS, personal fees from MSD, grants and personal fees from Roche, grants and personal fees from Fabre, grants and personal fees from Sanofi, outside the submitted work. Dr. Fargnoli reports grants and personal fees from Almirall, grants and personal fees from Leo Pharma, personal fees from Janssen, grants and personal fees from Novartis, personal fees from Lilly, grants and personal fees from Sanofi, personal fees from UCB, grants and personal fees from AbbVie, personal fees from Celgene, personal fees from Pierre Fabre, grants and personal fees from Galderma, personal fees from Mylan, personal fees from Medac Pharma, personal fees from Roche, personal fees from Sun Pharma, outside the submitted work. Dr. Forsea reports scientific consultant/speaker fee from Novartis, Leo Pharma, Solartium, Pierre Fabre, outside the submitted work. Dr. Frenard has nothing to disclose. Dr. Harwood reports institutional research grants and honoraria from Sanofi, Novartis, Merck, Pfizer, Galderma, Meda, Almirall, PellePharm, Leo Pharma, Ceries. Dr. Hauschild reports honoraria and/or research grants from Almirall, BMS, Roche, Novartis, Pierre Fabre, Sun Pharma, Merck Serono, Sanofi-Aventis, Regeneron, MSD/Merck, Philogen, OncoSec outside the submitted work. Dr. Hoeller reports grants and personal fees from Amgen, personal fees from BMS, personal fees from MSD, personal fees from Novartis, personal fees from Pierre Fabre, personal fees from Roche, personal fees from Sanofi, personal fees from Incyte, outside the submitted work. Dr. Kandolf-Sekulovic reports speakers? honoraria for Roche, Novartis, MSD, BMS, Janssen outside the submitted work. Dr. Kaufmann reports institutional research grants (clinical trials) from AbbVie, Amgen, Biontech, BMS, Celgene, Galderma, Janssen, Leo, Lilly, Merck, MSD, Novartis, Pierre Fabre, Pfizer, Regeneron, Roche, Wyeth. Advisory board and honoraria from Merz, Roche, Novartis. Dr. Kelleners-Smeets reports grants from Netherlands Organization for Health Research and Development, other from Janssen-Cilag, other from AbbVie, other from Galderma, outside the submitted work. Dr. Malvehy reports research grants from Almirall, ISDIN, Leo Pharma, Galderma, GSK, Cantabria, participation in advisory board meetings for Almirall, Sun Pharma, BMS, Roche, Novartis, Pierre Fabre. Dr. del Marmol reports personal fees from MSD, from BMS, personal fees from Sanofi, grants and personal fees from AbbVie, grants from Janssen, outside the submitted work. Dr. Middleton reports personal fees and/or grants from Amgen, Roche, AstraZeneca, GSK, Novartis, Immunocore, BMS, Eisai and Merck. Institutional funding from Millennium, Vertex, Pfizer, Regeneron, TC Biopharm, BioLineRx, Replimune, outside the submitted work. Dr. Moreno-Ram?rez has nothing to disclose. Dr. Pellecani reports grants from university of Modena and Reggio Emilia, during the conduct of the study, grants from Novartis, grants and personal fees from Almirall, grants from Leo Pharma, from null, outside the submitted work. Dr. Peris reports honoraria for advisory board and grants from AbbVie, Almirall, Biogen Celgene, Lilly, Galderma, Leo Pharma, Novartis, Roche, Sanofi, Sun Pharma, Sandoz outside the submitted work. Dr. Saiag reports honoraria for advisory board and grants from Amgen, Bristol-Myers Squibb, MSD, Merck Serono, Novartis, Pfizer, Roche-Genentech, Pierre Fabre, and Sanofi, outside the submitted work. Dr. van den Beuken-van Everdingen has nothing to disclose. Dr. Vieira has nothing to disclose. Dr. Zalaudek reports honoraria and advisory board and grants from Sanofi, Sun Pharma, Novartis, Galderma, Roche, Celgene, Almirall, Leo Pharma, Mylan, Difa Cooper, Cieffe Labs, La Roche Posay, Pierre Fabre. Dr. Eggermont reports over the last 5 years personal fees as a consultant advisor for BIOCAD, BioInvent, Bristol-Myers Squibb (BMS), CatalYm, Ellipses, GlaxoSmithKline (GSK), HalioDx, Incyte, IO Biotech, ISA Pharmaceuticals, Merck Sharpe & Dohme (MSD), Novartis, Pfizer, Polynoma, Regeneron, Sanofi, SELLAS, SkylineDx. Dr. Grob reports personal fees for advisory board and as speaker from Amgen, Roche, GSK, Novartis, BMS, Pierre Fabre, Merck, Sanofi, Merck, Pfizer outside the submitted work., Dr. Stratigos reports personal fees and/or research support from Novartis, Roche, BMS, AbbVie, Sanofi, Regeneron, Genesis Pharma, outside the submitted work. Dr. Garbe reports personal fees from Amgen, personal fees from MSD, grants and personal fees from Novartis , grants and personal fees from NeraCare , grants and personal fees from BMS , personal fees from Pierre Fabre, personal fees from Philogen, grants and personal fees from Roche , grants and personal fees from Sanofi , outside the submitted work. Dr. Dessinioti has nothing to disclose. Dr. Lebbe reports grants and personal fees from Bristol-Myers Squibb , personal fees from MSD, personal fees from Novartis, personal fees from Amgen, grants and personal fees from Roche , personal fees from Avantis Medical Systems, personal fees from Pierre Fabre, personal fees from Pfizer, personal fees from Incyte, outside the submitted work. Dr. Bataille reports personal fees from Novartis, personal fees from Merck MSD, outside the submitted work. Dr. Bastholt reports personal fees for advisory board activity: BMS, Roche, Novartis, Pierre Fabre, AstraZeneca, Incyte, MSD/Merck, Bayer. Dr. Dréno reports grants and personal fees from BMS , personal fees from MSD, grants and personal fees from Roche , grants and personal fees from Fabre , grants and personal fees from Sanofi , outside the submitted work. Dr. Fargnoli reports grants and personal fees from Almirall , grants and personal fees from Leo Pharma , personal fees from Janssen, grants and personal fees from Novartis , personal fees from Lilly, grants and personal fees from Sanofi , personal fees from UCB, grants and personal fees from AbbVie , personal fees from Celgene, personal fees from Pierre Fabre, grants and personal fees from Galderma , personal fees from Mylan, personal fees from Medac Pharma, personal fees from Roche, personal fees from Sun Pharma, outside the submitted work. Dr. Forsea reports scientific consultant/speaker fee from Novartis, Leo Pharma, Solartium, Pierre Fabre, outside the submitted work. Dr. Frenard has nothing to disclose. Dr. Harwood reports institutional research grants and honoraria from Sanofi , Novartis , Merck , Pfizer , Galderma , Meda , Almirall , PellePharm , Leo Pharma , Ceries . Dr. Hauschild reports honoraria and/or research grants from Almirall , BMS , Roche , Novartis , Pierre Fabre , Sun Pharma , Merck Serono , Sanofi-Aventis , Regeneron , MSD/Merck , Philogen , OncoSec outside the submitted work. Dr. Hoeller reports grants and personal fees from Amgen , personal fees from BMS, personal fees from MSD, personal fees from Novartis, personal fees from Pierre Fabre, personal fees from Roche, personal fees from Sanofi, personal fees from Incyte, outside the submitted work. Dr. Kandolf-Sekulovic reports speakers’ honoraria for Roche, Novartis, MSD, BMS, Janssen outside the submitted work. Dr. Kaufmann reports institutional research grants (clinical trials) from AbbVie , Amgen , Biontech , BMS , Celgene , Galderma , Janssen , Leo , Lilly , Merck , MSD , Novartis , Pierre Fabre , Pfizer , Regeneron , Roche , Wyeth . Advisory board and honoraria from Merz, Roche, Novartis. Dr. Kelleners-Smeets reports grants from Netherlands Organization for Health Research and Development , other from Janssen-Cilag, other from AbbVie, other from Galderma, outside the submitted work. Dr. Malvehy reports research grants from Almirall , ISDIN , Leo Pharma , Galderma , GSK , Cantabria, participation in advisory board meetings for Almirall, Sun Pharma, BMS, Roche, Novartis, Pierre Fabre. Dr. del Marmol reports personal fees from MSD, from BMS, personal fees from Sanofi, grants and personal fees from AbbVie, grants from Janssen , outside the submitted work. Dr. Middleton reports personal fees and/or grants from Amgen , Roche , AstraZeneca , GSK , Novartis , Immunocore , BMS , Eisai and Merck . Institutional funding from Millennium , Vertex , Pfizer , Regeneron , TC Biopharm , BioLineRx , Replimune , outside the submitted work. Dr. Moreno-Ramírez has nothing to disclose. Dr. Pellecani reports grants from university of Modena and Reggio Emilia , during the conduct of the study, grants from Novartis , grants and personal fees from Almirall , grants from Leo Pharma , from null, outside the submitted work. Dr. Peris reports honoraria for advisory board and grants from AbbVie , Almirall , Biogen Celgene , Lilly , Galderma , Leo Pharma , Novartis , Roche , Sanofi , Sun Pharma , Sandoz outside the submitted work. Dr. Saiag reports honoraria for advisory board and grants from Amgen , Bristol-Myers Squibb , MSD , Merck Serono , Novartis , Pfizer , Roche-Genentech , Pierre Fabre , and Sanofi , outside the submitted work. Dr. van den Beuken-van Everdingen has nothing to disclose. Dr. Vieira has nothing to disclose. Dr. Zalaudek reports honoraria and advisory board and grants from Sanofi , Sun Pharma , Novartis , Galderma , Roche , Celgene , Almirall , Leo Pharma , Mylan , Difa Cooper , Cieffe Labs , La Roche Posay , Pierre Fabre . Dr. Eggermont reports over the last 5 years personal fees as a consultant advisor for BIOCAD, BioInvent, Bristol-Myers Squibb (BMS), CatalYm, Ellipses, GlaxoSmithKline (GSK), HalioDx, Incyte, IO Biotech, ISA Pharmaceuticals, Merck Sharpe & Dohme (MSD), Novartis, Pfizer, Polynoma, Regeneron, Sanofi, SELLAS, SkylineDx. Dr. Grob reports personal fees for advisory board and as speaker from Amgen, Roche, GSK, Novartis, BMS, Pierre Fabre, Merck, Sanofi, Merck, Pfizer outside the submitted work., European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organization for Research and Treatment of Cancer (EORTC), Stratigos, A. J., Garbe, C., Dessinioti, C., Lebbe, C., Bataille, V., Bastholt, L., Dreno, B., Concetta Fargnoli, M., Forsea, A. M., Frenard, C., Harwood, C. A., Hauschild, A., Hoeller, C., Kandolf-Sekulovic, L., Kaufmann, R., Kelleners-Smeets, N. W. J., Malvehy, J., del Marmol, V., Middleton, M. R., Moreno-Ramirez, D., Pellecani, G., Peris, K., Saiag, P., van den Beuken-van Everdingen, M. H. J., Vieira, R., Zalaudek, I., Eggermont, A. M. M., Grob, J. -J., Dermatologie, MUMC+: MA Dermatologie (9), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, RS: MHeNs - R3 - Neuroscience, Anesthesiologie, MUMC+: MA Anesthesiologie (9), and MUMC+: TPZ Palliatieve Zorg (9)
Subjects: 0301 basic medicine, Oncology, Cancer Research, Skin Neoplasms, medicine.medical_treatment, Dermatologic Surgical Procedures, Aftercare, Anti-PD-1 antibody, Cemiplimab, Chemotherapy, Cutaneous squamous cell carcinoma, EGFR inhibitors, Follow-up, Locally advanced, Metastatic, Radiotherapy, Surgical excision, Treatment, Medical Oncology, Metastasis, METASTATIC CUTANEOUS HEAD, 0302 clinical medicine, Antineoplastic Agents, Immunological, Quality of life, IN-TRANSIT METASTASIS, Monoclonal, ADJUVANT RADIOTHERAPY, Lymph node, Humanized, Societies, Medical, Skin, Cetuximab, Palliative Care, Margins of Excision, Chemoradiotherapy, 3. Good health, EGFR inhibitor, Dissection, medicine.anatomical_structure, Immunological, 030220 oncology & carcinogenesis, PHASE-II, Carcinoma, Squamous Cell, Sunlight, Settore MED/35 - MALATTIE CUTANEE E VENEREE, medicine.drug, medicine.medical_specialty, Consensus, Clinical Decision-Making, [SDV.CAN]Life Sciences [q-bio]/Cancer, Antineoplastic Agents, CERVICAL LYMPH-NODES, Dermatology, Antibodies, Monoclonal, Humanized, ELECTIVE NECK DISSECTION, Antibodies, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Patient Education as Topic, Internal medicine, Humans, Lymph Node Excision, Lymph Nodes, Neoplasm Staging, Patient Care Team, Medical, medicine, ORGAN TRANSPLANT RECIPIENTS, business.industry, Carcinoma, Guideline, medicine.disease, Cancérologie, Radiation therapy, 030104 developmental biology, Squamous Cell, INTERFERON-ALPHA, business, GROWTH-FACTOR RECEPTOR, Societies, INTRALESIONAL METHOTREXATE
Abstract: In order to update recommendations on treatment, supportive care, education and follow-up of patients with invasive cutaneous squamous cell carcinoma (cSCC), a multidisciplinary panel of experts from the European Dermatology Forum, the European Association of Dermato-Oncology and the European Organization of Research and Treatment of Cancer was formed. Recommendations were based on evidence-based literature review, guidelines and expert consensus. Treatment recommendations are presented for common primary cSCC (low risk, high risk), locally advanced cSCC, regional metastatic cSCC (operable or inoperable) and distant metastatic cSCC. For common primary cSCC (the most frequent cSCC type), first-line treatment is surgical excision with postoperative margin assessment or microscopically controlled sugery. Safety margins containing clinical normal-appearing tissue around the tumour during surgical excision and negative margins as reported in the pathology report are necessary to minimise the risk of local recurrence and metastasis. In case of positive margins, a re-excision shall be done, for operable cases. Lymph node dissection is recommended for cSCC with cytologically or histologically confirmed regional nodal involvement. Radiotherapy should be considered as curative treatment for inoperable cSCC, or for non-surgical candidates. Anti-PD-1 antibodies are the first-line systemic treatment for patients with metastatic or locally advanced cSCC who are not candidates for curative surgery or radiation, with cemiplimab being the first approved systemic agent for advanced cSCC by the Food and Drug Administration/European Medicines Agency. Second-line systemic treatments for advanced cSCC include epidermal growth factor receptor inhibitors (cetuximab) combined with chemotherapy or radiation therapy. Multidisciplinary board decisions are mandatory for all patients with advanced disease who require more than surgery. Patients should be engaged with informed decisions on management and be provided with best supportive care to optimise symptom management and improve quality of life. Frequency of follow-up visits and investigations for subsequent new cSCC depend on underlying risk characteristics., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2020

30. Extra-cellular vesicles carry proteome of cancer hallmarks

Author: Rune Matthiesen, Akhilesh Pandey, Ana Sofia Carvalho, Maria Carolina Strano Moraes, Bruno Costa Silva, Hans Christian Beck, Cristian Bodo, Manuel S. Rodriguez, Henrique Baeta, Mayank Saraswat, Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Champalimaud Centre for the Unknown [Lisbon], Odense University Hospital (OUH), Institut des Technologies Avancées en sciences du Vivant (ITAV), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut de pharmacologie et de biologie structurale (IPBS), National Institute of Mental Health and Neurosciences [Bangalore, Inde] (NIMHANS ), Manipal academy of Higher Education, SAP Labs India, Department of Laboratory Medicine and Pathology (Mayo Clinic Rochester), and Mayo Clinic [Rochester]
Subjects: 0301 basic medicine, Proteomics, Proteome, Angiogenesis, Review, Biology, Exosomes, Metastasis, Extracellular Vesicles, 03 medical and health sciences, 0302 clinical medicine, Cell Line, Tumor, Neoplasms, microRNA, medicine, Humans, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Oncogene Proteins, Cell growth, Tumor Suppressor Proteins, Cancer, medicine.disease, Cancer exosomes, Microvesicles, Cell biology, 030104 developmental biology, 030220 oncology & carcinogenesis, Drug resistance, Cancer extracellular microvesicles, Biomarkers, Signal Transduction
Abstract: International audience; Through lateral transfer, extra-cellular vesicles (EVs) transport their DNA, miRNA, mRNA and proteins such as enzymes mediating drug resistance, transporters as well as growth factors to neighboring cells. By virtue of this horizontal transfer, EVs potentially regulate cell growth, migration, angiogenesis and metastasis and increase tissue permeability in cancer. Furthermore, EVs regulate immune factors and allow the tumor cells to evade immune recognition and cell death. To explore if the proteomes of exosomes support functional transfer of cancer hallmarks, in this meta-analysis, we compared EVs and whole cell proteomes from the NCI-60 human tumor cell line panel. We observed a subgroup of proteins in each cancer hallmark signature as highly abundant and consistently expressed in EVs from all cell lines. Among these were oncoproteins frequently targeted in cancer therapies whose presence on EVs could potentially render therapies less effective by serving as decoys.
Published: 2020

31. The use of 5‐aminosalicylate for patients with Crohn’s disease in a prospective European inception cohort with 5 years follow‐up – an Epi‐IBD study

Author: Ravi Misra, Riina Salupere, Renata D'Incà, Pia Oksanen, Elena Belousova, Jens Kjeldsen, Pekka Collin, Vicent Hernandez, Naila Arebi, Laszlo Lakatos, Luísa Castro, Selwyn Odes, Hendrika Al Kievit, Corinne Gower-Rousseau, Shaji Sebastian, Ebbe Langholz, Jóngerð Midjord, Adrian Goldis, I. Kaimakliotis, Doron Schwartz, Dimitrios K. Christodoulou, Konstantinos H. Katsanos, Zeljko Krznaric, Pierre Ellul, Pia Munkholm, Daniel Bergemalm, Johan Burisch, Kelly Gatt, Juozas Kupcinskas, Jonas Halfvarson, K R Nielsen, Dana Duricova, Vibeke Andersen, Karina Winther Andersen, M. Giannotta, Svetlana Turcan, Martin Bortlik, Gediminas Kiudelis, Mathurin Fumery, Jens Frederik Dahlerup, Peter L. Lakatos, Natalia Pedersen, Fernando Magro, Alessandro Sartini, V Domislović, D. Valpiani, Luísa Barros, Örebro University, University Hospital Centre Zagreb, Partenaires INRAE, University of Zagreb, Victor Babeş University of Medicine and Pharmacy (UMFT), Aarhus University Hospital, Tampere University Hospital, University of Tampere [Finland], Complexo Hospitalario Universitario de Vigo, Université d'Etat de Médecine et Pharmacie, Chisinau, Republic of Moldova, Université d'Etat de Médecine et Pharmacie, Moscow Regional Research Clinical Institute (MONICA), Università degli Studi di Padova = University of Padua (Unipd), G.B. Morgagni-Pierantoni Hospital [Forlì, Italy], Azienda Usl Toscana centro [Firenze], Imperial College London, IBD clinical and research centre, ISCARE, Prague, Czech Republic, Charles University [Prague] (CU), Mater Dei Hospital [Malta], Odense University Hospital (OUH), University of Southern Denmark (SDU), University Hospital of Ioannina, University of Hull [United Kingdom], Centro Hospitalar Universitário de São João [Porto], Universidade do Porto = University of Porto, National Hospital of the Faroe Islands [Tórshavn, Faroe Islands], University of Tartu, Herning Hospital, Lithuanian University of health Sciences [Kaunas], CHU Amiens-Picardie, Service d'Epidémiologie et de Santé Publique [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Lille, Ben-Gurion University of the Negev (BGU), Semmelweis University [Budapest], McGill University Health Center [Montreal] (MUHC), and University of Copenhagen = Københavns Universitet (UCPH)
Subjects: Adult, Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], 5-aminosalicylates, Population-based cohort, disease course, Disease, Severity of Illness Index, Disease course, Maintenance Chemotherapy, Population based cohort, Biological Factors, Young Adult, Crohn Disease, Internal medicine, Medicine, Humans, Immunologic Factors, In patient, Prospective Studies, Mesalamine, 5-aminosalicylate, Colectomy, Crohn's disease, business.industry, Anti-Inflammatory Agents, Non-Steroidal, Inflammatory Bowel Disease, Gastroenterology, Middle Aged, medicine.disease, INCEPTION COHORT, Europe, Hospitalization, Treatment Outcome, Oncology, Disease Progression, Drug Therapy, Combination, Female, business, Follow-Up Studies
Abstract: BACKGROUND: The lack of scientific evidence regarding the effectiveness of 5-aminosalicylate in patients with Crohn's disease is in sharp contrast to its widespread use in clinical practice.AIMS: The aim of the study was to investigate the use of 5-aminosalicylate in patients with Crohn's disease as well as the disease course of a subgroup of patients who were treated with 5-aminosalicylate as maintenance monotherapy during the first year of disease.METHODS: In a European community-based inception cohort, 488 patients with Crohn's disease were followed from the time of their diagnosis. Information on clinical data, demographics, disease activity, medical therapy and rates of surgery, cancers and deaths was collected prospectively. Patient management was left to the discretion of the treating gastroenterologists.RESULTS: Overall, 292 (60%) patients with Crohn's disease received 5-aminosalicylate period during follow-up for a median duration of 28 months (interquartile range 6-60). Of these, 78 (16%) patients received 5-aminosalicylate monotherapy during the first year following diagnosis. Patients who received monotherapy with 5-aminosalicylate experienced a mild disease course with only nine (12%) who required hospitalization, surgery, or developed stricturing or penetrating disease, and most never needed more intensive therapy. The remaining 214 patients were treated with 5-aminosalicylate as the first maintenance drug although most eventually needed to step up to other treatments including immunomodulators (75 (35%)), biological therapy (49 (23%)) or surgery (38 (18%)).CONCLUSION: In this European community-based inception cohort of unselected Crohn's disease patients, 5-aminosalicylate was commonly used. A substantial group of these patients experienced a quiescent disease course without need of additional treatment during follow-up. Therefore, despite the controversy regarding the efficacy of 5-aminosalicylate in Crohn's disease, its use seems to result in a satisfying disease course for both patients and physicians.
Published: 2020

32. Overall survival at 5 years of follow-up in a phase III trial comparing ipilimumab 10 mg/kg with 3 mg/kg in patients with advanced melanoma

Author: Vanna Chiarion-Sileni, Céleste Lebbé, Catriona M. McNeil, Joanna Pikiel, Jean-Jacques Grob, Luc Thomas, Lars Bastholt, Andrzej Mackiewicz, Michele Maio, Omid Hamid, Virginia Ferraresi, Marta Nyakas, Caroline Robert, Michelle Del Vecchio, Burcin Simsek, Michael Smylie, Laurent Mortier, Dirk Schadendorf, Carmen Loquai, Inge Marie Svane, Ana Arance, Gabriella Liszkay, Fareeda Hosein, Piotr Rutkowski, Paolo A. Ascierto, Florent Grange, Christoph Hoeller, Brigitte Dréno, Ralf Gutzmer, Claus Garbe, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale [Naples, Italy] (INT-FGP), IRCCS Istituto Nazionale dei Tumori [Milano], Poznan University of Medical Sciences [Poland] (PUMS), Institut Gustave Roussy (IGR), Université Paris-Sud - Paris 11 (UP11), Oncologie dermatologique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Istituto Oncologico Veneto I.R.C.C.S. [Padova, Italy], Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), CIC Saint Louis (CIC-1427), Université Paris Diderot - Paris 7 (UPD7)-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), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Herlev and Gentofte Hospital, Copenhagen University Hospital, Royal Prince Alfred Hospital [Camperdown, Australia] (RPAH), Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), University Medical Center [Mainz], Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 (ONCO-THAI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Claude Huriez [Lille], CHU Lille, Odense University Hospital (OUH), Centre hospitalier universitaire de Nantes (CHU Nantes), University Hospital [Essen, Germany], German Cancer Consortium [Heidelberg] (DKTK), Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Oslo University Hospital [Oslo], Aix Marseille Université (AMU), Assistance Publique - Hôpitaux de Marseille (APHM), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), National Institute of Oncology [Budapest, Hungary], Cross Cancer Institute [Edmonton, AB, Canada], Medizinische Universität Wien = Medical University of Vienna, Regina Elena National Cancer Institute [Rome], Centre Hospitalier Universitaire de Reims (CHU Reims), Medizinische Hochschule Hannover (MHH), Wojewodzkie Centrum Oncologii [Gdańsk, Poland], Bristol-Myers Squibb [Princeton], University Hospital of Siena, and Malbec, Odile
Subjects: Cancer Research, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Immunology, Medizin, Ipilimumab, randomized trials, Gastroenterology, Asymptomatic, law.invention, immunology, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, medicine, Clinical endpoint, Immunology and Allergy, 030212 general & internal medicine, Adverse effect, RC254-282, Clinical/Translational Cancer Immunotherapy, Pharmacology, business.industry, Incidence (epidemiology), Melanoma, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, oncology, [SDV] Life Sciences [q-bio], Oncology, 030220 oncology & carcinogenesis, Molecular Medicine, medicine.symptom, business, Brain metastasis, medicine.drug
Abstract: BackgroundWe have previously reported significantly longer overall survival (OS) with ipilimumab 10 mg/kg versus ipilimumab 3 mg/kg in patients with advanced melanoma, with higher incidences of adverse events (AEs) at 10 mg/kg. This follow-up analysis reports a 5-year update of OS and safety.MethodsThis randomized, multicenter, double-blind, phase III trial included patients with untreated or previously treated unresectable stage III or IV melanoma. Patients were randomly assigned (1:1) to ipilimumab 10 mg/kg or 3 mg/kg every 3 weeks for 4 doses. The primary end point was OS.ResultsAt a minimum follow-up of 61 months, median OS was 15.7 months (95% CI 11.6 to 17.8) at 10 mg/kg and 11.5 months (95% CI 9.9 to 13.3) at 3 mg/kg (HR 0.84, 95% CI 0.71 to 0.99; p=0.04). In a subgroup analysis, median OS of patients with asymptomatic brain metastasis was 7.0 months (95% CI 4.0 to 12.8) in the 10 mg/kg group and 5.7 months (95% CI 4.2 to 7.0) in the 3 mg/kg group. In patients with wild-type or mutantBRAFtumors, median OS was 13.8 months (95% CI 10.2 to 17.0) and 33.2 months (95% CI 19.4 to 45.2) in the 10 mg/kg group, and 11.2 months (95% CI 9.2 to 13.8) and 19.7 months (95% CI 11.6 to 25.3) in the 3 mg/kg group, respectively. The incidence of grade 3/4 treatment-related AEs was 36% in the 10 mg/kg group vs 20% in the 3 mg/kg group, and deaths due to treatment-related AEs occurred in four (1%) and two patients (1%), respectively.ConclusionsThis 61-month follow-up of a phase III trial showed sustained long-term survival in patients with advanced melanoma who started metastatic treatment with ipilimumab monotherapy, and confirmed the significant benefit for those who received ipilimumab 10 mg/kg vs 3 mg/kg. These results suggest the emergence of a plateau in the OS curve, consistent with previous ipilimumab studies.Trial registration numberNCT01515189.
Published: 2020

33. European consensus-based interdisciplinary guideline for melanoma. Part 2: Treatment - Update 2019

Author: Garbe, Claus, Amaral, Teresa, Peris, Ketty, Hauschild, Axel, Arenberger, Petr, Bastholt, Lars, Bataille, Veronique, Del Marmol, Veronique, Dréno, Brigitte, Fargnoli, Maria Concetta, Grob, Jean-Jacques, Höller, Christoph, Kaufmann, Roland, Lallas, Aimilios, Lebbé, Celeste, Malvehy, Josep, Middleton, Mark, Moreno-Ramirez, David, Pellacani, Giovanni, Saiag, Philippe, Stratigos, Alexander J, Vieira, Ricardo, Zalaudek, Iris, Eggermont, Alexander M M, European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO), and the European Organization for Research and Treatment of Cancer (EORTC), Garbe, Clau, Amaral, Teresa, Peris, Ketty, Hauschild, Axel, Arenberger, Petr, Bastholt, Lar, Bataille, Veronique, Del Marmol, Veronique, Dréno, Brigitte, Fargnoli, Maria Concetta, Grob, Jean-Jacque, Höller, Christoph, Kaufmann, Roland, Lallas, Aimilio, Lebbé, Celeste, Malvehy, Josep, Middleton, Mark, Moreno-Ramirez, David, Pellacani, Giovanni, Saiag, Philippe, Stratigos, Alexander J, Vieira, Ricardo, Zalaudek, Iri, Eggermont, Alexander M M, Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Aix-Marseille Université - Faculté des sciences médicales et paramédicales (AMU SMPM), Aix Marseille Université (AMU), Service de Dermatologie [AP-HP Hôpital Saint-Louis], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Ambroise Paré [AP-HP], Novartis Les Laboratories Pierre Fabre Berlin Mathematical School, BMS AbbVie Sanofi Pfizer Amgen Eisai GlaxoSmithKline, GSK Roche DUSA Pharmaceuticals Merck KGaA Meso Scale Diagnostics, MSD, C.G. reports receiving personal fees from Amgen, Pierre Fabre, Philogen and MSD, and reports receiving grants and personal fees from Novartis, NeraCare, BMS, Roche and Sanofi, outside the submitted work.T.A. reports receiving personal fees and other grants from BMS, Novartis, Pierre Fabre, Neracare and Sanofi, outside the submitted work.K.P. reports receiving personal fees from Novartis, Roche, Sanofi, Lilly, Leopharma, Pierre Fabre, Almirall and Celgene, outside the submitted work.A.H. reports receiving grants and personal fees from Amgen, BMS, MerckSerono, MSD / Merck, Philogen, Pierre Fabre, Provectus, Regeneron, Roche, Sanofi-Genzyme, and Novartis Pharma, receiving personal fees from OncoSec and Sun Pharma, outside the submitted work.P.A. reports receiving personal fees from Amgen, MSD, Novartis, BMS and Roche, outside the submitted work.L.B. reports receiving grants from BMS, during the conduct of the study, personal fees from BMS, Novartis, Merck MSD, Roche, Incyte, Bayer, outside the submitted work.V.B. reports receiving personal fees from Novartis and Merck MSD, outside the submitted work.V.d.M. reports receiving personal fees from MSD, BMS and Sanofi, grants and personal fees from ABVIE, grants from Jansen, outside the submitted work.B.M. reports grants and personal fees from BMS, Roche, Fabre and Sanofi, personal fees from MSD, outside the submitted work.M.C.F. reports receiving grants and personal fees from Almirall, Leo Pharma, Novartis, Sanofi, Abbvie and Galderma, personal fees from Janssen, Lilly, UCB, Celgene, Pierre Fabre, Mylan, Medac Pharma, Roche, Sun Pharma, outside the submitted work.J.J.G. reports receiving personal fees from Amgen, MSD, Novartis, BMS, Roche, Pierre fabre, MercK / Pfizer, outside the submitted work.C.H. reports receiving personal fees from Amgen, MSD, Novartis, Incyte, BMS, Pierre Fabre, Roche, Sanofi, outside the submitted work.R.K. reports receiving grants and personal fees from Novartis and Roche, and grants from AbbVie, Amgen, Bionteck, BMS, Celgene, Galderma, Janssen, Leo, Lilly, Merck, MSD, Pierre Fabre, Regeneron and Wyeth, outside the submitted work.A.L. reports personal fees from Amgen, Novartis, BMS and, Sanofi grants and personal fees from Roche, outside the submitted work.C.L. reports receiving grants and personal fees from Bristol-Myers Squibb and Roche, personal fees from MSD, Novartis, Amgen, Avantis Medical Systems, Pierre Fabre, Pfizer, Incyte, outside the submitted work.J.M. reports personal fees from Amgen, personal fees from MSD, grants from Novartis, grants and personal fees from BMS, grants and personal fees from Roche, grants and personal fees from Almirall, personal fees from Sun Pharma, outside the submitted work.M.M. reports receiving personal fees from Amgen and BiolineRx, grants and personal fees from Roche and GSK, grants from Astrazeneca, personal fees and other from Novartis, Eisai, Array Biopharma (now Pfizer), Rigontec (acquired by MSD), and BMS, other from Millennium, Regeneron Pfizer, personal fees, non-financial support and other from Immunocore, Replimun and Merck / MSD, outside the submitted work.G.P. reports receiving personal fees from Novartis, personal fees from Sanofi, grants from Novartis, instruments from 3Gen, Vidix, Fotofinder and MAVIG GmbH, outside the submitted work.P.S. reports receiving personal fees from Amgen, MSD and Pierre Fabre / array, grants and personal fees from Novartis, NeraCare, BMS, Roche, and Sanofi, outside the submitted work.A.J.S. reports personal fees and/or research support from Novartis, Roche, BMS, Abbvie, Sanofi, Regeneron, Genesis Pharma, outside the submitted work. Dr. Vieira has nothing to disclose.I.Z. reports receiving personal fees from Difa Cooper, MSD, Sanofi, Almirall Hermal, Novartis, Mylan and Sunpharma, grants and personal fees from Roche, outside the submitted work.A.M.M.E. reports receiving personal fees from Biocad, Biovent, BMS, CatalYm, Ellipses, GSK, Incyte, IO Biotech, ISA Pharmaceuticals, Merck GmbH, MSD, Novartis, Pfizer, Polynoma, Regeneron, Sanofi, SkylineDx, Stellas, other from RiverD, SkylineDx, Theranovir, all outside the submitted work., Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Portuguese Air Force Health Care Direction [Lisbon, Portugal] (PAFHCD), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, University Medical Center of Schleswig–Holstein = Universitätsklinikum Schleswig-Holstein (UKSH), Kiel University, Charles University [Prague] (CU), Odense University Hospital (OUH), King‘s College London, Université libre de Bruxelles (ULB), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), University of L'Aquila [Italy] (UNIVAQ), Assistance Publique - Hôpitaux de Marseille (APHM), Medizinische Universität Wien = Medical University of Vienna, Frankfurt University Hospital, Aristotle University of Thessaloniki, Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), University of Oxford, Hospital Universitario Virgen Macarena [Séville], University - Hospital of Modena and Reggio Emilia [Modena, Italy], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Athens Medical School [Athens], Universidade de Coimbra [Coimbra], Università degli studi di Trieste = University of Trieste, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Princess Máxima Center for Pediatric Oncology, and Dupuis, Christine
Subjects: 0301 basic medicine, Oncology, Cancer Research, [SDV]Life Sciences [q-bio], Systemic treatment, Primary diagnosis, 0302 clinical medicine, Dermatoscopy, Stage (cooking), Melanoma, Trametinib, Adjuvant treatment, Cutaneous melanoma, Excisional margins, Interferon-α, Metastasectomy, Sentinel lymph node dissection, Tumour thickness, Combined Modality Therapy, 3. Good health, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Practice Guidelines as Topic, Excisional margin, Confocal reflectance microscopy, Settore MED/35 - MALATTIE CUTANEE E VENEREE, medicine.drug, Diagnostic Imaging, medicine.medical_specialty, Consensus, Follow-up examinations, Sentinel lymph node, Mutation testing, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, AJCC classification, Internal medicine, medicine, Humans, European Union, Neoplasm Staging, Interdisciplinary Communication, Total body photography, business.industry, Cancer, Dabrafenib, Guideline, medicine.disease, Imaging diagnostics, Cancérologie, 030104 developmental biology, Sequential digital dermatoscopy, business
Abstract: A unique collaboration of multidisciplinary experts from the European Dermatology Forum, the European Association of Dermato-Oncology and the European Organization for Research and Treatment of Cancer (EORTC) was formed to make recommendations on cutaneous melanoma diagnosis and treatment, based on systematic literature reviews and the experts' experience. Cutaneous melanomas are excised with 1- to 2-cm safety margins. Sentinel lymph node dissection shall be performed as a staging procedure in patients with tumour thickness ≥1.0 mm or ≥0.8 mm with additional histological risk factors, although there is as yet no clear survival benefit for this approach. Therapeutic decisions in stage III/IV patients should be primarily made by an interdisciplinary oncology team (“Tumor Board”). Adjuvant therapies in stage III/IV patients are primarily anti–PD-1, independent of mutational status, or dabrafenib plus trametinib for BRAF-mutant patients. In distant metastasis, either resected or not, systemic treatment is indicated. For first-line treatment, particularly in BRAF wild-type patients, immunotherapy with PD-1 antibodies alone or in combination with CTLA-4 antibodies shall be considered. In particular scenarios for patients with stage IV melanoma and a BRAF-V600 E/K mutation, first-line therapy with BRAF/MEK inhibitors can be offered as an alternative to immunotherapy. In patients with primary resistance to immunotherapy and harbouring a BRAF-V600 E/K mutation, this therapy shall be offered in second-line. Systemic therapy in stage III/IV melanoma is a rapidly changing landscape, and it is likely that these recommendations may change in the near future., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2019

34. Impact of Abiraterone Acetate plus Prednisone or Enzalutamide on Patient-reported Outcomes in Patients with Metastatic Castration-resistant Prostate Cancer: Final 12-mo Analysis from the Observational AQUARiUS Study

Author: Antoine Thiery-Vuillemin, Mads Hvid Poulsen, Edouard Lagneau, M Lukac, Dominique Beal-Ardisson, A. Birtle, Louis Marie Dourthe, Alison Reid, Guillaume Ploussard, Geneviève Pissart, Elias Pintus, Suzy Van Sanden, Florence Lefresne, Redas Trepiakas, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Odense University Hospital (OUH), Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Clinique La Croix du Sud, Royal Preston Hospital [Preston, UK] (RPH), Clinique Sainte Anne [Strasbourg], Hôpital privé Jean Mermoz [Lyon], Frimley Health NHS Foundation Trust [Slough], Zealand University Hospital [Naestved, Denmark], Janssen Pharmaceutica N.V. [Beerse, Belgium], Parexel International Czech Republic s.r.o, The Royal Marsden NHS Foundation Trust [Sutton, UK], AQUARiUS Investigators, CCSD, Accord Elsevier, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])
Subjects: Quality of life, Oncology, Male, medicine.medical_specialty, Time Factors, [SDV]Life Sciences [q-bio], Urology, AQUARiUS, 030232 urology & nephrology, Abiraterone Acetate, Antineoplastic Agents, 03 medical and health sciences, chemistry.chemical_compound, Prostate cancer, 0302 clinical medicine, Prednisone, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Nitriles, Phenylthiohydantoin, Enzalutamide, medicine, Humans, Patient Reported Outcome Measures, Prospective Studies, Neoplasm Metastasis, Abiraterone, Aged, Aged, 80 and over, Patient-reported outcomes, business.industry, Abiraterone acetate, Repeated measures design, Cancer, medicine.disease, Metastatic castration-resistant prostate cancer, 3. Good health, [SDV] Life Sciences [q-bio], Prostatic Neoplasms, Castration-Resistant, chemistry, 030220 oncology & carcinogenesis, Benzamides, Observational study, business, medicine.drug
Abstract: International audience; Background: Few studies have examined patient-reported outcomes (PROs) with abiraterone acetate plus prednisone (abiraterone) versus enzalutamide in metastatic castration-resistant prostate cancer (mCRPC).Objective: To determine the impact of abiraterone and enzalutamide on PROs.Design, setting, and participants: AQUARiUS (NCT02813408) was a prospective, 12-mo, observational study in patients with mCRPC from Denmark, France, and the UK.Intervention: Abiraterone or enzalutamide treatment according to routine practise.Outcome measurements and statistical analysis: PROs were collected over 12 mo using Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog), Brief Fatigue Inventory-Short Form (BFI-SF), Brief Pain Inventory-Short Form, and European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (QLQ-C30) at baseline and routine visits. Outcomes included mean change in PROs, patients with clinically meaningful worsening (CMW) in PROs, and safety. Data were analysed using repeated measures linear and logistic models adjusted for baseline characteristics.Results and limitations: Abiraterone-treated (N = 105) and enzalutamide-treated (N = 106) patients were included. Key PRO items (cognitive impairments and fatigue) were significantly (p < 0.05) in favour of abiraterone versus enzalutamide during the study. "Perceived cognitive impairment" and "comments from others" (FACT-Cog); "fatigue right now", "usual level of fatigue", and "worst level of fatigue" (BFI-SF); and "cognitive functioning" and "fatigue" (QLQ-C30) were significantly in favour of abiraterone over enzalutamide for three or more consecutive periods up to month 12. From study initiation, significantly fewer patients receiving abiraterone experienced one or more CMW episode in cognition and fatigue. Fatigue and asthenia (adverse events) were lower with abiraterone than with enzalutamide (5% vs 15% and 10% vs 11%, respectively). There were no treatment-related deaths. Limitations included lack of randomisation.Conclusions: In a real-world setting, this 12-mo analysis suggests an advantage of abiraterone acetate plus prednisone over enzalutamide on fatigue and cognitive function; this finding occurred early after treatment initiation. This difference should be considered when choosing treatment.Patient summary: This study looked at the effect of two treatments (abiraterone acetate plus prednisone and enzalutamide) for metastatic castration-resistant prostate cancer on patient quality of life over 12 mo. Using established questionnaires, patients reported that they experienced less fatigue and cognitive impairments (including memory loss and reduced thinking abilities) with abiraterone acetate plus prednisone than with enzalutamide.
Published: 2019

35. A short leucocyte telomere length is associated with development of insulin resistance

Author: Carlos Labat, Simon Verhulst, Kirsten Ohm Kyvik, Athanase Benetos, Kaare Christensen, Christine Dalgård, Simon Toupance, Masayuki Kimura, Abraham Aviv, Jeremy D. Kark, Groningen Institute for Evolutionary Life Sciences [Groningen] (GELIFES), University of Groningen [Groningen], University of Southern Denmark (SDU), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Hadassah School of Public Health and Community Medicine, The Hebrew University of Jerusalem (HUJ), Center of Human Development and Aging, New Jersey Medical School, Rutgers New Jersey Medical School (NJMS), Rutgers University System (Rutgers)-Rutgers University System (Rutgers), The Danish Twin Registry, Odense Patient Data Explorative Network (OPEN), Odense University Hospital (OUH), Service de Gériatrie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), NIH grants AG030678 and HD071180, the Danish Council for Independent Research – Medical Sciences, the INTERREG 4 A – programme Southern DenmarkSchleswig-K.E.R.N. supported by the European Regional DevelopmentFund, A.P. Møller Foundation for the Advancement of Medical Science, French National Research Agency (ANR), Translationnelle: N°ID RCB: 2014-A00298-39: 2014-2017, and Verhulst lab
Subjects: Male, 0301 basic medicine, Endocrinology, Diabetes and Metabolism, 030204 cardiovascular system & hematology, Body Mass Index, GLUCOSE, 0302 clinical medicine, Genetics/epidemiology (all), Risk Factors, MESH: Risk Factors, GLYCEMIA, Leukocytes, Longitudinal cohort, OXIDATIVE STRESS, METABOLIC SYNDROME, 2. Zero hunger, education.field_of_study, MESH: Middle Aged, Age Factors, Middle Aged, Telomere, MESH: Insulin Resistance, Cardiovascular Diseases, OBESITY, Female, STRONG HEART FAMILY, Human, Adult, medicine.medical_specialty, Population, Cardiovascular risk factors, BIOLOGY, Biology, MESH: Body Mass Index, MESH: Leukocytes, 03 medical and health sciences, Sex Factors, Insulin resistance, MESH: Sex Factors, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, INFLAMMATION, Internal medicine, Internal Medicine, medicine, Humans, education, MESH: Age Factors, MESH: Humans, Insulin sensitivity and resistance, Type 2 Diabetes Mellitus, MESH: Cardiovascular Diseases, MESH: Adult, ADULTS, medicine.disease, Obesity, MESH: Male, AMERICAN-INDIANS, 030104 developmental biology, Endocrinology, Insulin Resistance, Metabolic syndrome, MESH: Telomere, MESH: Female
Abstract: AIMS/HYPOTHESIS: A number of studies have shown that leucocyte telomere length (LTL) is inversely associated with insulin resistance and type 2 diabetes mellitus. The aim of the present longitudinal cohort study, utilising a twin design, was to assess whether shorter LTL predicts insulin resistance or is a consequence thereof. METHODS: Participants were recruited between 1997 and 2000 through the population-based national Danish Twin Registry to participate in the GEMINAKAR study, a longitudinal evaluation of metabolic disorders and cardiovascular risk factors. Baseline and follow-up measurements of LTL and insulin resistance over an average of 12 years were performed in a subset of the Registry consisting of 338 (184 monozygotic and 154 dizygotic) same-sex twin pairs. RESULTS: Age at baseline examination was 37.4 ± 9.6 (mean ± SD) years. Baseline insulin resistance was not associated with age-dependent changes in LTL (attrition) over the follow-up period, whereas baseline LTL was associated with changes in insulin resistance during this period. The shorter the LTL at baseline, the more pronounced was the increase in insulin resistance over the follow-up period (p AIMS/HYPOTHESIS: A number of studies have shown that leucocyte telomere length (LTL) is inversely associated with insulin resistance and type 2 diabetes mellitus. The aim of the present longitudinal cohort study, utilising a twin design, was to assess whether shorter LTL predicts insulin resistance or is a consequence thereof.METHODS: Participants were recruited between 1997 and 2000 through the population-based national Danish Twin Registry to participate in the GEMINAKAR study, a longitudinal evaluation of metabolic disorders and cardiovascular risk factors. Baseline and follow-up measurements of LTL and insulin resistance over an average of 12 years were performed in a subset of the Registry consisting of 338 (184 monozygotic and 154 dizygotic) same-sex twin pairs.RESULTS: Age at baseline examination was 37.4 ± 9.6 (mean ± SD) years. Baseline insulin resistance was not associated with age-dependent changes in LTL (attrition) over the follow-up period, whereas baseline LTL was associated with changes in insulin resistance during this period. The shorter the LTL at baseline, the more pronounced was the increase in insulin resistance over the follow-up period (p CONCLUSIONS/INTERPRETATION: These findings suggest that individuals with short LTL are more likely to develop insulin resistance later in life. By contrast, presence of insulin resistance does not accelerate LTL attrition.
Published: 2016

36. Natural Disease Course of Ulcerative Colitis During the First Five Years of Follow-up in a European Population-based Inception Cohort-An Epi-IBD Study

Author: Selwyn Odes, Riina Salupere, Pekka Collin, Konstantinos H. Katsanos, Dana Duricova, Hendrika Adriana Linda Kievit, I. Kaimakliotis, Jóngerð Midjord, Dimitrios K. Christodoulou, Johan Burisch, Carl Eriksson, Luísa Castro, Ebbe Langholz, Vibeke Andersen, Jonas Halfvarson, Pierre Ellul, Naila Arebi, Pia Oksanen, Pia Munkholm, Shaji Sebastian, K R Nielsen, Elena Belousova, Renata D'Incà, Inna Nikulina, Jens Kjeldsen, Marko Brinar, Limas Kupčinskas, Vicent Hernandez, Gediminas Kiudelis, Karina Winther Andersen, Zsuzsanna Vegh, Alina Toca, Corinne Gower-Rousseau, Svetlana Turcan, Martin Bortlik, Adrian Goldis, Natalia Pedersen, Mathurin Fumery, Peter L. Lakatos, Fernando Magro, Silvija Čuković-Čavka, Ravi Misra, Stefania Chetcuti Zammit, Doron Schwartz, D. Valpiani, Luísa Barros, Sally Myers, University of Copenhagen = Københavns Universitet (UCPH), University Hospital of Ioannina, Centro Hospitalar Universitário de São João [Porto], Universidade do Porto = University of Porto, Odense University Hospital (OUH), Semmelweis University [Budapest], McGill University Health Center [Montreal] (MUHC), Örebro University, CHU Amiens-Picardie, Registre EPIMAD, CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Amiens-Picardie-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Epidémiologie et de Santé Publique [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), University Hospital Centre Zagreb, Partenaires INRAE, University of Zagreb, Moscow Regional Research Clinical Institute (MONICA), Hull and East Yorkshire Eye Hospital, Lithuanian University of health Sciences [Kaunas], Ben-Gurion University of the Negev (BGU), G.B. Morgagni-Pierantoni Hospital [Forlì, Italy], Università degli Studi di Padova = University of Padua (Unipd), University of Tartu, Mater Dei Hospital [Malta], ISCARE, Charles University [Prague] (CU), Victor Babeş University of Medicine and Pharmacy (UMFT), University research clinic [Herning, Denmark], State University of Moldova, National Hospital of the Faroe Islands [Tórshavn, Faroe Islands], Viborg Hospital, Regional Hospital West Jutland [Denmark], University of Southern Denmark (SDU), St Mark's Hospital, Tampere University Hospital, University of Tampere [Finland], and Instituto de Investigación Sanitaria Galicia Sur [Vigo, Spain]
Subjects: Adult, Male, medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Population, Inflammatory bowel disease, surgery, 03 medical and health sciences, 0302 clinical medicine, Gastrointestinal Agents, Internal medicine, medicine, Humans, Immunologic Factors, biologics, Prospective Studies, Prospective cohort study, education, Colectomy, education.field_of_study, treatment, business.industry, hospitalisation, Hazard ratio, Gastroenterology, General Medicine, Middle Aged, medicine.disease, Ulcerative colitis, Europe, Hospitalization, 030220 oncology & carcinogenesis, Cohort, Disease Progression, 030211 gastroenterology & hepatology, Colitis, Ulcerative, Female, prognosis, business, Cohort study, Follow-Up Studies
Abstract: Background and Aims: Few population-based cohort studies have assessed the disease course of ulcerative colitis [UC] in the era of biological therapy and widespread use of immunomodulators. The aim of this study was to assess the 5-year outcome and disease course of patients with UC in the Epi-IBD cohort.Methods: In a prospective, population-based inception cohort of unselected patients with UC, patients were followed up from the time of their diagnosis, which included the collection of their clinical data, demographics, disease activity, medical therapy, and rates of surgery, cancers, and deaths. Associations between outcomes and multiple covariates were analysed by Cox regression analysis.Results: A total of 717 patients were included in the study. During follow-up, 43 [6%] patients underwent a colectomy and 163 [23%] patients were hospitalised. Of patients with limited colitis [distal to the left flexure], 90 [21%] progressed to extensive colitis. In addition, 92 [27%] patients with extensive colitis experienced a regression in disease extent, which was associated with a reduced risk of hospitalisation (hazard ratio [HR]: 0.5 95% CI: 0.3-0.8]. Overall, patients were treated similarly in both geographical regions; 80 [11%] patients needed biological therapy and 210 [29%] patients received immunomodulators. Treatment with immunomodulators was found to reduce the risk of hospitalisation [HR: 0.5 95% CI: 0.3-0.8].Conclusions: Although patients in this population-based cohort were treated more aggressively with immunomodulators and biological therapy than in cohorts from the previous two decades, their disease outcomes, including colectomy rates, were no different. However, treatment with immunomodulators was found to reduce the risk of hospitalisation.
Published: 2018

37. Quantifying the effects of 16p11.2 copy number variants on brain structure: A multisite genetic-first study

Author: Sandra Martin-Brevet, Borja Rodríguez-Herreros, Jared A. Nielsen, Clara Moreau, Claudia Modenato, Anne M. Maillard, Aurélie Pain, Sonia Richetin, Aia E. Jønch, Abid Y. Qureshi, Nicole R. Zürcher, Philippe Conus, Wendy K. Chung, Elliott H. Sherr, John E. Spiro, Ferath Kherif, Jacques S. Beckmann, Nouchine Hadjikhani, Alexandre Reymond, Randy L. Buckner, Bogdan Draganski, Sébastien Jacquemont, Marie-Claude Addor, Joris Andrieux, Benoît Arveiler, Geneviève Baujat, Frédérique Sloan-Béna, Marco Belfiore, Dominique Bonneau, Sonia Bouquillon, Odile Boute, Alfredo Brusco, Tiffany Busa, Jean-Hubert Caberg, Dominique Campion, Vanessa Colombert, Marie-Pierre Cordier, Albert David, François-Guillaume Debray, Marie-Ange Delrue, Martine Doco-Fenzy, Ulrike Dunkhase-Heinl, Patrick Edery, Christina Fagerberg, Laurence Faivre, Francesca Forzano, David Genevieve, Marion Gérard, Daniela Giachino, Agnès Guichet, Olivier Guillin, Delphine Héron, Bertrand Isidor, Aurélia Jacquette, Sylvie Jaillard, Hubert Journel, Boris Keren, Didier Lacombe, Sébastien Lebon, Cédric Le Caignec, Marie-Pierre Lemaître, James Lespinasse, Michèle Mathieu-Dramart, Sandra Mercier, Cyril Mignot, Chantal Missirian, Florence Petit, Kristina Pilekær Sørensen, Lucile Pinson, Ghislaine Plessis, Fabienne Prieur, Caroline Rooryck-Thambo, Massimiliano Rossi, Damien Sanlaville, Britta Schlott Kristiansen, Caroline Schluth-Bolard, Marianne Till, Mieke Van Haelst, Lionel Van Maldergem, Hanalore Alupay, Benjamin Aaronson, Sean Ackerman, Katy Ankenman, Ayesha Anwar, Constance Atwell, Alexandra Bowe, Arthur L. Beaudet, Marta Benedetti, Jessica Berg, Jeffrey Berman, Leandra N. Berry, Audrey L. Bibb, Lisa Blaskey, Jonathan Brennan, Christie M. Brewton, Randy Buckner, Polina Bukshpun, Jordan Burko, Phil Cali, Bettina Cerban, Yishin Chang, Maxwell Cheong, Vivian Chow, Zili Chu, Darina Chudnovskaya, Lauren Cornew, Corby Dale, John Dell, Allison G. Dempsey, Trent Deschamps, Rachel Earl, James Edgar, Jenna Elgin, Jennifer Endre Olson, Yolanda L. Evans, Anne Findlay, Gerald D. Fischbach, Charlie Fisk, Brieana Fregeau, Bill Gaetz, Leah Gaetz, Silvia Garza, Jennifer Gerdts, Orit Glenn, Sarah E. Gobuty, Rachel Golembski, Marion Greenup, Kory Heiken, Katherine Hines, Leighton Hinkley, Frank I. Jackson, Julian Jenkins, Rita J. Jeremy, Kelly Johnson, Stephen M. Kanne, Sudha Kessler, Sarah Y. Khan, Matthew Ku, Emily Kuschner, Anna L. Laakman, Peter Lam, Morgan W. Lasala, Hana Lee, Kevin LaGuerre, Susan Levy, Alyss Lian Cavanagh, Ashlie V. Llorens, Katherine Loftus Campe, Tracy L. Luks, Elysa J. Marco, Stephen Martin, Alastair J. Martin, Gabriela Marzano, Christina Masson, Kathleen E. McGovern, Rebecca McNally Keehn, David T. Miller, Fiona K. Miller, Timothy J. Moss, Rebecca Murray, Srikantan S. Nagarajan, Kerri P. Nowell, Julia Owen, Andrea M. Paal, Alan Packer, Patricia Z. Page, Brianna M. Paul, Alana Peters, Danica Peterson, Annapurna Poduri, Nicholas J. Pojman, Ken Porche, Monica B. Proud, Saba Qasmieh, Melissa B. Ramocki, Beau Reilly, Timothy P.L. Roberts, Dennis Shaw, Tuhin Sinha, Bethanny Smith-Packard, Anne Snow Gallagher, Vivek Swarnakar, Tony Thieu, Christina Triantafallou, Roger Vaughan, Mari Wakahiro, Arianne Wallace, Tracey Ward, Julia Wenegrat, Anne Wolken, 16p11.2 European Consortium, Simons Variation in Individuals Project (VIP) Consortium, CSIR-Institute of Microbial Technology [Chandigarh] (IMTech), Council of Scientific and Industrial Research [India] (CSIR), Service Hospitalier Frédéric Joliot (SHFJ), 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, Human Genetics, Gillberg Neuropsychiatry Centre [Göteborg, Sueden], Institute of Neuroscience and Physiology [Göteborg]-University of Gothenburg (GU), The Wellcome Trust Sanger Institute [Cambridge], Department of Psychiatry [Boston], Massachusetts General Hospital [Boston], Service de génétique médicale, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Laboratoire de Génétique Clinique, Hôpital Jeanne de Flandre [Lille]-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire de Génétique Humaine, Développement et Cancer, Université Bordeaux Segalen - Bordeaux 2, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Génétique Médicale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Guglielmo Marconi University [Roma], Laboratoire de biomécanique (LBM), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13), Systèmes de Référence Temps Espace (SYRTE), Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Génétique clinique, Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Department of Medical Sciences, Università degli studi di Torino (UNITO), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique du cancer et des maladies neuropsychiatriques (GMFC), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Liège (CHU-Liège), Service de cytogénétique constitutionnelle, Hospices Civils de Lyon (HCL)-CHU de Lyon-Centre Neuroscience et Recherche, Department of Clinical Genetics, Vejle Hospital, Institute of Child Health, Département de génétique médicale, maladies rares et médecine personnalisée [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de génétique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Génétique médicale et fonctionnelle du cancer et des maladies neuropsychiatriques, 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 Génétique Médicale, Centre hospitalier universitaire de Nantes (CHU Nantes), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [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 de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Génétique Médicale, Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA)-Hôpital Chubert, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Physiopathologie et neuroprotection des atteintes du cerveau en développement, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Génétique Chromosomique, Bâtiment Hôtel Dieu - Centre Hospitalier de Chambéry, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Service de génétique, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Génétique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Génétique Clinique Chromosomique et Moléculaire, CHU Saint-Etienne, CHU Bordeaux [Bordeaux], Hospices Civils de Lyon (HCL), Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Department of Genomics of Common Disease, Imperial College London, Regional Hospital, Department of Psychiatry and Behavioral Sciences! (UW psychiatry), University of Washington [Seattle], University of California, San Francisco (UCSF), UCSF, Unité de Recherches Zootechniques (URZ), Institut National de la Recherche Agronomique (INRA), University of California [San Francisco] (UCSF), University of California, UCL Institute of Neurology, Biomagnetic Imaging Laboratory - University of California, SFARI219193, Simons Foundation, 31003A160203, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Roger De Spoelberch, Partridge Foundations, Jeanne et Jean Louis Levesque Foundation, 604102, Seventh Framework Programme, Canada Research Chairs, CRSII33-133044, SNSF Sinergia, 32003B_159780, SNSF National Centre of Competence in Research Synapsy, Foundation Parkinson Switzerland, Foundation Synapsis, Université de Lausanne = University of Lausanne (UNIL), CHU Sainte Justine [Montréal], Harvard University [Cambridge], Odense University Hospital (OUH), Department of radiology (Massachusetts General Hospital), Department of Psychiatry Massachusetts General Hospital (MGH), Columbia University [New York], Simons Foundation, University of California [San Francisco] (UC San Francisco), University of California (UC), University of Gothenburg (GU), Centre de recherche du CHU Sainte-Justine / Research Center of the Sainte-Justine University Hospital [Montreal, Canada], Université de Montréal (UdeM)-CHU Sainte Justine [Montréal], Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Università degli studi di Torino = University of Turin (UNITO), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Vejle Hospital [Danemark], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Harvard University, Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), University of Lausanne (UNIL), Centre de recherche du CHU Sainte-Justine [Montreal], Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Reproduction & Development (AR&D), Human genetics, Institute of Microbial Technology (IMTECH), Intitute of Microbial Technology, Gillberg Neuropsychiatry Centre, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], PSL Research University (PSL)-PSL Research University (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Département de génétique médicale, maladies rares et médecine personnalisée [CHRU de Montpellier], Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [APHP], Centre Hospitalier Bretagne Atlantique-Hôpital Chubert, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Pitié-Salpêtrière [APHP], Centre de recherche Jean-Pierre Aubert-Neurosciences et Cancer, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, 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 Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Addor, M.C., Andrieux, J., Arveiler, B., Baujat, G., Sloan-Béna, F., Belfiore, M., Bonneau, D., Bouquillon, S., Boute, O., Brusco, A., Busa, T., Caberg, J.H., Campion, D., Colombert, V., Cordier, M.P., David, A., Debray, F.G., Delrue, M.A., Doco-Fenzy, M., Dunkhase-Heinl, U., Edery, P., Fagerberg, C., Faivre, L., Forzano, F., Genevieve, D., Gérard, M., Giachino, D., Guichet, A., Guillin, O., Héron, D., Isidor, B., Jacquette, A., Jaillard, S., Journel, H., Keren, B., Lacombe, D., Lebon, S., Le Caignec, C., Lemaître, M.P., Lespinasse, J., Mathieu-Dramart, M., Mercier, S., Mignot, C., Missirian, C., Petit, F., Pilekær Sørensen, K., Pinson, L., Plessis, G., Prieur, F., Rooryck-Thambo, C., Rossi, M., Sanlaville, D., Schlott Kristiansen, B., Schluth-Bolard, C., Till, M., Van Haelst, M., Van Maldergem, L., Alupay, H., Aaronson, B., Ackerman, S., Ankenman, K., Anwar, A., Atwell, C., Bowe, A., Beaudet, A.L., Benedetti, M., Berg, J., Berman, J., Berry, L.N., Bibb, A.L., Blaskey, L., Brennan, J., Brewton, C.M., Buckner, R., Bukshpun, P., Burko, J., Cali, P., Cerban, B., Chang, Y., Cheong, M., Chow, V., Chu, Z., Chudnovskaya, D., Cornew, L., Dale, C., Dell, J., Dempsey, A.G., Deschamps, T., Earl, R., Edgar, J., Elgin, J., Olson, J.E., Evans, Y.L., Findlay, A., Fischbach, G.D., Fisk, C., Fregeau, B., Gaetz, B., Gaetz, L., Garza, S., Gerdts, J., Glenn, O., Gobuty, S.E., Golembski, R., Greenup, M., Heiken, K., Hines, K., Hinkley, L., Jackson, F.I., Jenkins, J., Jeremy, R.J., Johnson, K., Kanne, S.M., Kessler, S., Khan, S.Y., Ku, M., Kuschner, E., Laakman, A.L., Lam, P., Lasala, M.W., Lee, H., LaGuerre, K., Levy, S., Cavanagh, A.L., Llorens, A.V., Campe, K.L., Luks, T.L., Marco, E.J., Martin, S., Martin, A.J., Marzano, G., Masson, C., McGovern, K.E., McNally Keehn, R., Miller, D.T., Miller, F.K., Moss, T.J., Murray, R., Nagarajan, S.S., Nowell, K.P., Owen, J., Paal, A.M., Packer, A., Page, P.Z., Paul, B.M., Peters, A., Peterson, D., Poduri, A., Pojman, N.J., Porche, K., Proud, M.B., Qasmieh, S., Ramocki, M.B., Reilly, B., Roberts, TPL, Shaw, D., Sinha, T., Smith-Packard, B., Gallagher, A.S., Swarnakar, V., Thieu, T., Triantafallou, C., Vaughan, R., Wakahiro, M., Wallace, A., Ward, T., Wenegrat, J., and Wolken, A.
Subjects: Adult, Male, 0301 basic medicine, Adolescent, DNA Copy Number Variations, [SDV]Life Sciences [q-bio], Autism Spectrum Disorder/diagnostic imaging, Autism Spectrum Disorder/genetics, Brain/pathology, Child, Chromosome Deletion, Chromosome Duplication, Chromosomes, Human, Pair 16/genetics, Cognitive Dysfunction/diagnostic imaging, Cognitive Dysfunction/genetics, Female, Humans, Intellectual Disability/diagnostic imaging, Intellectual Disability/genetics, Language, Magnetic Resonance Imaging, Middle Aged, Neurodevelopmental Disorders/diagnostic imaging, Neurodevelopmental Disorders/genetics, Schizophrenia/diagnostic imaging, Schizophrenia/genetics, Young Adult, 16p11.2, Autism spectrum disorder, Copy number variant, Genetics, Imaging, Neurodevelopmental disorders, Biology, Biological Psychiatry, 03 medical and health sciences, 0302 clinical medicine, Transverse temporal gyrus, Neuroimaging, Intellectual Disability, medicine, Cognitive Dysfunction, Copy-number variation, ComputingMilieux_MISCELLANEOUS, Brain morphometry, Brain, medicine.disease, 16p112, 030104 developmental biology, Schizophrenia, Williams syndrome, Neuroscience, Insula, Chromosomes, Human, Pair 16, 030217 neurology & neurosurgery
Abstract: BACKGROUND: 16p11.2 breakpoint 4 to 5 copy number variants (CNVs) increase the risk for developing autism spectrum disorder, schizophrenia, and language and cognitive impairment. In this multisite study, we aimed to quantify the effect of 16p11.2 CNVs on brain structure.METHODS: Using voxel- and surface-based brain morphometric methods, we analyzed structural magnetic resonance imaging collected at seven sites from 78 individuals with a deletion, 71 individuals with a duplication, and 212 individuals without a CNV.RESULTS: Beyond the 16p11.2-related mirror effect on global brain morphometry, we observe regional mirror differences in the insula (deletion > control > duplication). Other regions are preferentially affected by either the deletion or the duplication: the calcarine cortex and transverse temporal gyrus (deletion > control; Cohen's d > 1), the superior and middle temporal gyri (deletion < control; Cohen's d < -1), and the caudate and hippocampus (control > duplication; -0.5 > Cohen's d > -1). Measures of cognition, language, and social responsiveness and the presence of psychiatric diagnoses do not influence these results.CONCLUSIONS: The global and regional effects on brain morphometry due to 16p11.2 CNVs generalize across site, computational method, age, and sex. Effect sizes on neuroimaging and cognitive traits are comparable. Findings partially overlap with results of meta-analyses performed across psychiatric disorders. However, the lack of correlation between morphometric and clinical measures suggests that CNV-associated brain changes contribute to clinical manifestations but require additional factors for the development of the disorder. These findings highlight the power of genetic risk factors as a complement to studying groups defined by behavioral criteria.
Published: 2018

38. Identification and characterization of two functional variants in the human longevity gene FOXO3

Author: Susanne Sebens, Wolfgang Lieb, Anne Luzius, Carolin Knecht, Marianne Nygaard, Nandini Badarinarayan, Robert Häsler, Sandra May, Marlene Jentzsch, Gerald Rimbach, Friederike Flachsbart, Andre Franke, Claudia Geismann, Almut Nebel, Stefan Schreiber, Dmitriy Drichel, Céline Derbois, Ben Krause-Kyora, Michael Nothnagel, Amke Caliebe, Hélène Blanché, Guillermo G. Torres, Kaare Christensen, Lene Christiansen, Michael Forster, Liljana Gentschew, Jean-François Deleuze, Andreas Till, Philip Rosenstiel, Alexander Arlt, Janina Dose, Abdou ElSharawy, Pilar Galan, Kathrin Pallauf, Flachsbart, Friederike, Dose, Janina, Nebel, Almut, Christian-Albrechts University of Kiel, University Hospital Schleswig-Holstein, University of Southern Denmark (SDU), Faculty of Sciences, Division of Biochemistry, Chemistry Department, Damietta University, Institute of Human Nutrition and Food Science, Rheinische Friedrich-Wilhelms-Universität Bonn, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Sorbonne Paris Cité (COMUE) (USPC), University of Cologne, Max Planck Institute for the Science of Human History (MPI-SHH), Max-Planck-Gesellschaft, Fondation Jean Dausset - Centre d’Étude du Polymorphisme Humain, Odense University Hospital (OUH), Deutsche Forschungsgemeinschaft (DFG) [NE 1191/1-1], Cluster of Excellence 'Inflammation at Interfaces', Medical Faculty of Kiel University, German Federal Ministry of Education and Research (BMBF) [01ZX1306A], BMBF [01EY1103], Land Schleswig-Holstein within the funding program Open Access Publikationsfonds, Ministère de l'Enseignement supérieur et de la Recherche, French Institut National de la Santé et de la Recherche Médicale, Institut National de la Recherche Agronomique, Université Paris 13, Commissariat à l'Energie Atomique-Centre National de Génotypage, VELUX Foundation, National Program for Research Infrastructure [09-063256], US National Institutes of Health-National Institute on Aging [P01 AG08761], Danish Agency for Science, Technology and Innovation [09-070081], National Research Foundation, and Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], media_common.quotation_subject, In silico, Science, General Physics and Astronomy, Locus (genetics), Biology, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Journal Article, Allele, lcsh:Science, Enhancer, Gene, media_common, Genetics, Multidisciplinary, Longevity, General Chemistry, 030104 developmental biology, CTCF, Expression quantitative trait loci, lcsh:Q
Abstract: FOXO3 is consistently annotated as a human longevity gene. However, functional variants and underlying mechanisms for the association remain unknown. Here, we perform resequencing of the FOXO3 locus and single-nucleotide variant (SNV) genotyping in three European populations. We find two FOXO3 SNVs, rs12206094 and rs4946935, to be most significantly associated with longevity and further characterize them functionally. We experimentally validate the in silico predicted allele-dependent binding of transcription factors (CTCF, SRF) to the SNVs. Specifically, in luciferase reporter assays, the longevity alleles of both variants show considerable enhancer activities that are reversed by IGF-1 treatment. An eQTL database search reveals that the alleles are also associated with higher FOXO3 mRNA expression in various human tissues, which is in line with observations in long-lived model organisms. In summary, we present experimental evidence for a functional link between common intronic variants in FOXO3 and human longevity., FOXO3 is one of the few established longevity genes. Here, the authors fine-map the FOXO3-longevity association to two intronic SNPs and, using luciferase assays and EMSAs, show that these SNPs affect binding of transcription factors CTCF and SRF and associate with FOXO3 expression.
Published: 2017

39. Immunochip analysis identifies association of the RAD50/IL13 region with human longevity

Author: Martina Müller-Nurasyid, Amke Caliebe, Céline Derbois, Friederike Flachsbart, Carsten Büning, Anette Peters, Pilar Galan, Per Hoffmann, Marianne Nygaard, Stephan Brand, Stefan Schreiber, Femke-Anouska Heinsen, Almut Nebel, Andre Franke, Markus M. Nöthen, Wolfgang Lieb, Liljana Gentschew, Kaare Christensen, David Ellinghaus, Lene Christiansen, Hélène Blanché, Konstantin Strauch, Jean-François Deleuze, Institute of Clinical Molecular Biology, Kiel University, Christian-Albrechts University of Kiel, University of Southern Denmark (SDU), Department of Clinical Genetics, Odense University Hospital, Odense University Hospital (OUH), Centre d'Etude du Polymorphisme Humain (CEPH), Fondation Jean Dausset-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Université Sorbonne Paris Cité (COMUE) (USPC), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Ludwig Maximilians University of Munich, Institute of Epidemiology, Helmholtz-Zentrum München (HZM), Munich Heart Alliance, German Center for Diabetes Research - Deutsches Zentrum für Diabetesforschung [Neuherberg] (DZD), German Research Center for Environmental Health - Helmholtz Center München (GmbH), Institute of Human Genetics, Universität Ulm - Ulm University [Ulm, Allemagne], Department of Genomics, Life and Brain Center, University of Bonn, Department of Biomedicine, University of Bergen (UiB), University Hospital Basel [Basel], University Medical Center Schleswig-Holstein, RESOLVE project [FP7-HEALTH-F4-2008-202047], Deutsche Forschungsgemeinschaft (DFG) Cluster of Excellence 'Inflammation at Interfaces', German Federal Ministry of Education and Research (BMBF) [01ZX1306A], German Ministry for Education and Research [01EY1103], German Federal Ministry for Education and Research within the context of the National Genome Research Network 2 [NGFN-2], National Genome Research Network plus (NGFNplus), Integrated Genome Research Network (IG) MooDS [01GS08144, 01GS08147], INTER-REG4A program Syddanmark-Schleswig-K.E.R.N, EU funds from the European Regional Development Fund, VELUX Foundation, Danish National Research Foundation, US National Institutes of Health-National Institute on Aging [P01 AG08761], Danish Agency for Science, Technology and Innovation [09-070081], French Institut National de la Sante et de la Recherche Medicale, Institut National de la Recherche Agronomique, the Universite Paris 13, Helmholtz Zentrum Munchen-German Research Center for Environmental Health, German Federal Ministry of Education and Research, State of Bavaria, Munich Center of Health Sciences (MC Health), Ludwig-Maximilians-University Munich, as part of LMUinnovativ, DFG [BR1912/6-1], Else-Kroner-Fresenius-Stiftung [2010_EKES.32], Alfried Krupp von Bohlen und Halbach-Stiftung, Heinz Nixdorf Foundation (Germany), German Ministry of Education and Science, German Research Council (DFG) [SI 236/8-1, SI236/9-1, ER 155/61], Université Paris Diderot - Paris 7 (UPD7)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Fondation Jean Dausset, Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Ludwig-Maximilians University [Munich] (LMU), Helmholtz Zentrum München = German Research Center for Environmental Health, Universität Bonn = University of Bonn, ProdInra, Migration, Flachsbart, Friederike, and Ellinghaus, David
Subjects: 0301 basic medicine, Il13, Rad50, 5q31.1, Immunochip, Genetic Association, Human Longevity, Aging, IL 13, genetic association, media_common.quotation_subject, [SDV]Life Sciences [q-bio], Longevity, Locus (genetics), Single-nucleotide polymorphism, Genome-wide association study, 030105 genetics & heredity, Biology, Danish, 03 medical and health sciences, Humans, SNP, chromosome, 5q31, human longevity, IL13, RAD50, longévité, Oligonucleotide Array Sequence Analysis, media_common, Genetic association, Short Takes, Genetics, Interleukin-13, Short Take, Cell Biology, language.human_language, Acid Anhydride Hydrolases, 3. Good health, DNA-Binding Proteins, [SDV] Life Sciences [q-bio], DNA Repair Enzymes, 030104 developmental biology, Genetic Loci, Multiple comparisons problem, language, Chromosomes, Human, Pair 5, Genome-Wide Association Study
Abstract: Human longevity is characterized by a remarkable lack of confirmed genetic associations. Here, we report on the identification of a novel locus for longevity in the RAD50/IL13 region on chromosome 5q31.1 using a combined European sample of 3208 long-lived individuals (LLI) and 8919 younger controls. First, we performed a large-scale association study on 1458 German LLI (mean age 99.0 years) and 6368 controls (mean age 57.2 years) by targeting known immune-associated loci covered by the Immunochip. The analysis of 142 136 autosomal single nucleotide polymorphisms (SNPs) revealed an Immunochip-wide significant signal (PI mmunochip = 7.01 × 10-9 ) for the SNP rs2075650 in the TOMM40/APOE region, which has been previously described in the context of human longevity. To identify novel susceptibility loci, we selected 15 markers with PI mmunochip < 5 × 10-4 for replication in two samples from France (1257 LLI, mean age 102.4 years; 1811 controls, mean age 49.1 years) and Denmark (493 LLI, mean age 96.2 years; 740 controls, mean age 63.1 years). The association at SNP rs2706372 replicated in the French study collection and showed a similar trend in the Danish participants and was also significant in a meta-analysis of the combined French and Danish data after adjusting for multiple testing. In a meta-analysis of all three samples, rs2706372 reached a P-value of PI mmunochip+Repl = 5.42 × 10-7 (OR = 1.20; 95% CI = 1.12-1.28). SNP rs2706372 is located in the extended RAD50/IL13 region. RAD50 seems a plausible longevity candidate due to its involvement in DNA repair and inflammation. Further studies are needed to identify the functional variant(s) that predispose(s) to a long and healthy life. Human longevity is characterized by a remarkable lack of confirmed genetic associations. Here, we report on the identification of a novel locus for longevity in the RAD50/IL13 region on chromosome 5q31.1 using a combined European sample of 3208 long-lived individuals (LLI) and 8919 younger controls. First, we performed a large-scale association study on 1458 German LLI (mean age 99.0 years) and 6368 controls (mean age 57.2 years) by targeting known immune-associated loci covered by the Immunochip. The analysis of 142 136 autosomal single nucleotide polymorphisms (SNPs) revealed an Immunochip-wide significant signal (PI mmunochip = 7.01 × 10(-9) ) for the SNP rs2075650 in the TOMM40/APOE region, which has been previously described in the context of human longevity. To identify novel susceptibility loci, we selected 15 markers with PI mmunochip < 5 × 10(-4) for replication in two samples from France (1257 LLI, mean age 102.4 years; 1811 controls, mean age 49.1 years) and Denmark (493 LLI, mean age 96.2 years; 740 controls, mean age 63.1 years). The association at SNP rs2706372 replicated in the French study collection and showed a similar trend in the Danish participants and was also significant in a meta-analysis of the combined French and Danish data after adjusting for multiple testing. In a meta-analysis of all three samples, rs2706372 reached a P-value of PI mmunochip+Repl = 5.42 × 10(-7) (OR = 1.20; 95% CI = 1.12-1.28). SNP rs2706372 is located in the extended RAD50/IL13 region. RAD50 seems a plausible longevity candidate due to its involvement in DNA repair and inflammation. Further studies are needed to identify the functional variant(s) that predispose(s) to a long and healthy life.
Published: 2016

40. Health and function assessments in two adjacent Danish birth cohorts of centenarians:Impact of design and methodology

Author: Karen Andersen-Ranberg, Kaare Christensen, Bernard Jeune, Sonja Vestergaard, Jean-Marie Robine, Axel Skytthe, University of Southern Denmark (SDU), Odense University Hospital (OUH), Mécanismes moléculaires dans les démences neurodégénératives (MMDN), Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), CERMES3 - Centre de recherche Médecine, sciences, santé, santé mentale, société (CERMES3 - UMR 8211 / U988 / UM 7), and École des hautes études en sciences sociales (EHESS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Gerontology, medicine.medical_specialty, Health (social science), Activities of daily living, Bathing, Physical performance, Danish, 03 medical and health sciences, 0302 clinical medicine, Cognition, Centenarians, medicine, Participation rate, 030212 general & internal medicine, Cognitive skill, Functional ability, Original Investigation, Public health, language.human_language, Toileting, language, Geriatrics and Gerontology, Psychology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract: International audience; Using the results from measures of functional ability, cognitive and physical performance from two adjacent birth cohorts of 100-year-old adults, we aimed to elucidate the possible impact of difference in participation rates, design, and interviewer mode. Participants were birth cohort members born in 1910 (DK-1910) and 1911-12 (DK-1911). Both surveys used the same assessment instruments, but the design was different, and data collection was carried out by trained survey agency interviewers in DK-1910 and trained nurses in DK-1911. Participation rate in DK-1911 (49.8 % (251/504)) was lower than in DK-1910 (66.9 % (273/408)) (p
Published: 2016

41. Meta-Analysis of Cell-based CaRdiac stUdiEs (ACCRUE) in patients with acute myocardial infarction based on individual patient data

Author: Gyongyosi, M., Wojakowski, W., Lemarchand, P., Lunde, K., Tendera, M., Bartunek, J., Marban, E., Assmus, B., Henry, T.D., Traverse, J.H., Moye, L.A., Surder, D., Corti, R., Huikuri, H., Miettinen, J., Wohrle, J., Obradovic, S., Roncalli, J., Malliaras, K., Pokushalov, E., Romanov, A., Kastrup, J., Bergmann, M.W., Atsma, D.E., Diederichsen, A., Edes, I., Benedek, I., Benedek, T., Pejkov, H., Nyolczas, N., Pavo, N., Bergler-Klein, J., Pavo, I.J., Sylven, C., Berti, S., Navarese, E.P., Maurer, G., ACCRUE Investigators, Department of Cardiology [Vienna], Medizinische Universität Wien = Medical University of Vienna, Third Division of Cardiology, Medical University of Silesia, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Department of Cardiology, Rikshospitalet-Oslo University Hospital [Oslo], department organization Studies, Boston College (BC), Cedars-Sinai Medical Center, Department of Medicine III, Goethe-Universität Frankfurt am Main, Dpt of Neurology [Minneapolis], University of Minnesota [Twin Cities] (UMN), University of Minnesota System-University of Minnesota System, Minneapolis Heart Institute, University of Minnesota System-University of Minnesota System-Abbott Northwestern Hospital, Coordinating Center for Clinical Trials, The University of Texas Health Science Center at Houston (UTHealth), Cardiocentro Ticino [Lugano], Universität Zürich [Zürich] = University of Zurich (UZH), Milieux aquatiques, écologie et pollutions (UR MALY), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Medical Research Center Oulu, University of Oulu, Cardiology Department [Ulm], Universität Ulm - Ulm University [Ulm, Allemagne], Clinic of Emergency Medicine, Military Medical Academy [Serbia], Service de cardiologie [Toulouse], Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], State Research Institute of Circulation Pathology, Department of Drug Design and Pharmacology [Copenhagen] (ILF), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Asklepios Klinik St. Georg, Cardiology Department [Leiden], Leiden University Medical Center (LUMC), Cardiology Department [Odense], Odense University Hospital (OUH), Cardiology Department [Debrecen], University of Debrecen, Cardiology Department [Târgu Mureș], University of Medicine and Pharmacy of Târgu Mureș, University Clinic for Cardiology, Medical Centre [Budapest], Hungarian Defense Forces -Ministry of Defence [Budapest], Karolinska Institutet [Stockholm], Invasive Cardiology [Pisa], National Research Council Institute of Clinical Physiology (CNR-IFC), Internal Medicine [Düsseldorf], Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf]-Division of Cardiology, Pulmonology and Vascular Medicine, TIME and LateTIME were supported by a grant from the National Heart, Lung, and Blood Institute under the cooperative agreement 5 UM1 HL087318-01. Part of the study was supported by European Union structural funds (Innovative Economy Operational Program POIG.01.01.02-00-109/09-00) to Dr Wojakowski., Medical University of Silesia (SUM), Unité de recherche de l'institut du thorax (ITX-lab), Service Cardiologie [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Lemarchand, Patricia, University of Zurich, Gyongyosi, M, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Minnesota [Twin Cities], University of Zürich [Zürich] (UZH), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Odense University Hospital, and Heinrich-Heine-Universität Düsseldorf [Düsseldorf]-Division of Cardiology, Pulmonology and Vascular Medicine
Subjects: Male, Time Factors, MESH: Chi-Square Distribution, Databases, Factual, Physiology, analysis, MESH: Myocardial Contraction, Myocardial Infarction, heart failure, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, MESH: Stroke Volume, Ventricular Function, Left, MESH: Ventricular Function, Left, MESH: Proportional Hazards Models, 0302 clinical medicine, Recurrence, Risk Factors, MESH: Risk Factors, Myocardial infarction, Prospective Studies, MESH: Bone Marrow Transplantation, Stroke, Bone Marrow Transplantation, Randomized Controlled Trials as Topic, MESH: Treatment Outcome, MESH: Aged, 0303 health sciences, Ejection fraction, MESH: Middle Aged, Ventricular Remodeling, Hazard ratio, MESH: Regeneration, Stroke volume, Middle Aged, MESH: Recovery of Function, 3. Good health, MESH: Myocardial Infarction, Treatment Outcome, Cardiology, Female, MESH: Cerebrovascular Disorders, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, MESH: Myocardium, 610 Medicine & health, MESH: Ventricular Remodeling, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, meta, Disease-Free Survival, 11171 Cardiocentro Ticino, 2705 Cardiology and Cardiovascular Medicine, 03 medical and health sciences, stem cells, Internal medicine, medicine, Humans, Regeneration, cardiovascular diseases, Ventricular remodeling, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, outcome assessment, End-systolic volume, MESH: Kaplan-Meier Estimate, 030304 developmental biology, Aged, Proportional Hazards Models, Chi-Square Distribution, MESH: Humans, business.industry, Myocardium, MESH: Time Factors, Stroke Volume, Recovery of Function, 1314 Physiology, medicine.disease, Myocardial Contraction, MESH: Databases, Factual, anterior wall myocardial infarction, MESH: Male, MESH: Prospective Studies, MESH: Recurrence, meta-analysis, Cerebrovascular Disorders, MESH: Randomized Controlled Trials as Topic, Heart failure, MESH: Disease-Free Survival, business, MESH: Female
Abstract: Rationale : The meta-Analysis of Cell-based CaRdiac study is the first prospectively declared collaborative multinational database, including individual data of patients with ischemic heart disease treated with cell therapy. Objective : We analyzed the safety and efficacy of intracoronary cell therapy after acute myocardial infarction (AMI), including individual patient data from 12 randomized trials (ASTAMI, Aalst, BOOST, BONAMI, CADUCEUS, FINCELL, REGENT, REPAIR-AMI, SCAMI, SWISS-AMI, TIME, LATE-TIME; n=1252). Methods and Results : The primary end point was freedom from combined major adverse cardiac and cerebrovascular events (including all-cause death, AMI recurrance, stroke, and target vessel revascularization). The secondary end point was freedom from hard clinical end points (death, AMI recurrence, or stroke), assessed with random-effects meta-analyses and Cox regressions for interactions. Secondary efficacy end points included changes in end-diastolic volume, end-systolic volume, and ejection fraction, analyzed with random-effects meta-analyses and ANCOVA. We reported weighted mean differences between cell therapy and control groups. No effect of cell therapy on major adverse cardiac and cerebrovascular events (14.0% versus 16.3%; hazard ratio, 0.86; 95% confidence interval, 0.63–1.18) or death (1.4% versus 2.1%) or death/AMI recurrence/stroke (2.9% versus 4.7%) was identified in comparison with controls. No changes in ejection fraction (mean difference: 0.96%; 95% confidence interval, −0.2 to 2.1), end-diastolic volume, or systolic volume were observed compared with controls. These results were not influenced by anterior AMI location, reduced baseline ejection fraction, or the use of MRI for assessing left ventricular parameters. Conclusions : This meta-analysis of individual patient data from randomized trials in patients with recent AMI revealed that intracoronary cell therapy provided no benefit, in terms of clinical events or changes in left ventricular function. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01098591.
Published: 2015

42. DCAF4, a novel gene associated with leucocyte telomere length

Author: Mangino, Massimo, Christiansen, Dan, Stone, Rivka, Hunt, Steven, Horvath, Kent, Eisenberg, Dan, Kimura, Masayuki, Petersen, Inge, Kark, Jeremy, Herbig, Utz, Reiner, Alex, Benetos, Athanase, Codd, Veryan, Nyholt, Dale, Sinnreich, Ronit, Christensen, Kaare, Nassar, Hisham, Hwang, Shih-Jen, Levy, Daniel, Bataille, Veronique, Fitzpatrick, Annette, Chen, Wei, Berenson, Gerald, Samani, Nilesh, Martin, Nicholas, Tishkoff, Sarah, Schork, Nicholas, Kyvik, Kirsten Ohm, Dalgård, Christine, Spector, Timothy, Aviv, Abraham, Department of Twin Research and Genetic Epidemiology, King's College London, London, The Danish Aging Research Center, Epidemiology, Institute of Public Health, University of Southern Denmark (SDU), The Danish Twin Registry, Department of Clinical Biochemistry and Pharmacology, OdenseUniversity Hospital, Sdr. Boulevard 29, Rutgers New Jersey Medical School (NJMS), Rutgers University System (Rutgers), University of Utah School of Medicine [Salt Lake City], Center for Studies in Demography and Ecology, University of Washington [Seattle], Department of Anthropology, Washington State University, Washington State University (WSU), Center of Human Development and Aging, New Jersey Medical School, Rutgers University System (Rutgers)-Rutgers University System (Rutgers), Hadassah School of Public Health and Community Medicine, The Hebrew University of Jerusalem (HUJ), Department of Epidemiology, University of Washington, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de Gériatrie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Department of Cardiovascular Sciences [Leicester], University of Leicester, National Institute for Health Research (NIHR), QIMR Berghofer Medical Research Institute, Hadassah Hebrew University Medical Center [Jerusalem], National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), Department of Twin Research & Genetic Epidemiology, King's College London, Tulane Center for Cardiovascular Health, Tulane University Health Sciences Center, Leicester NIHR Biomedical Research Unit in Cardiovascular Disease, University of Pennsylvania [Philadelphia], Department of Molecular and Experimental Medicine, The Scripps Research Institute, The Scripps Research Institute, Institute of Regional Health Services Research, Odense Patient Data Explorative Network (OPEN), Odense University Hospital (OUH), and University of Southern Denmark, Institute of Public Health
Subjects: skin, MESH: Melanoma, MESH: Carrier Proteins, MESH: Telomere Homeostasis, complex traits, MESH: Leukocytes, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Risk Factors, MESH: Risk Factors, Leukocytes, melanoma, cancer, Humans, Alleles, telomere, MESH: Humans, MESH: Alleles, Telomere Homeostasis, Complex traits, Telomere, cancer: skin, MESH: Gene Expression Regulation, Gene Expression Regulation, MESH: Genome-Wide Association Study, Carrier Proteins, MESH: Telomere, Genome-Wide Studies, Genome-Wide Association Study
Abstract: BACKGROUND: Leucocyte telomere length (LTL), which is fashioned by multiple genes, has been linked to a host of human diseases, including sporadic melanoma. A number of genes associated with LTL have already been identified through genome-wide association studies. The main aim of this study was to establish whether DCAF4 (DDB1 and CUL4-associated factor 4) is associated with LTL. In addition, using ingenuity pathway analysis (IPA), we examined whether LTL-associated genes in the general population might partially explain the inherently longer LTL in patients with sporadic melanoma, the risk for which is increased with ultraviolet radiation (UVR). RESULTS: Genome-wide association (GWA) meta-analysis and de novo genotyping of 20 022 individuals revealed a novel association (p=6.4×10(-10)) between LTL and rs2535913, which lies within DCAF4. Notably, eQTL analysis showed that rs2535913 is associated with decline in DCAF4 expressions in both lymphoblastoid cells and sun-exposed skin (p=4.1×10(-3) and 2×10(-3), respectively). Moreover, IPA revealed that LTL-associated genes, derived from GWA meta-analysis (N=9190), are over-represented among genes engaged in melanoma pathways. Meeting increasingly stringent p value thresholds (pBACKGROUND: Leucocyte telomere length (LTL), which is fashioned by multiple genes, has been linked to a host of human diseases, including sporadic melanoma. A number of genes associated with LTL have already been identified through genome-wide association studies. The main aim of this study was to establish whether DCAF4 (DDB1 and CUL4-associated factor 4) is associated with LTL. In addition, using ingenuity pathway analysis (IPA), we examined whether LTL-associated genes in the general population might partially explain the inherently longer LTL in patients with sporadic melanoma, the risk for which is increased with ultraviolet radiation (UVR).RESULTS: Genome-wide association (GWA) meta-analysis and de novo genotyping of 20 022 individuals revealed a novel association (p=6.4×10(-10)) between LTL and rs2535913, which lies within DCAF4. Notably, eQTL analysis showed that rs2535913 is associated with decline in DCAF4 expressions in both lymphoblastoid cells and sun-exposed skin (p=4.1×10(-3) and 2×10(-3), respectively). Moreover, IPA revealed that LTL-associated genes, derived from GWA meta-analysis (N=9190), are over-represented among genes engaged in melanoma pathways. Meeting increasingly stringent p value thresholds (pCONCLUSIONS: We uncovered a new locus associated with LTL in the general population. We also provided preliminary findings that suggest a link of LTL through genetic mechanisms with UVR and melanoma in the general population.
Published: 2015

43. Sex difference in leukocyte telomere length is ablated in opposite-sex co-twins

Author: Carlos Labat, Kirsten Ohm Kyvik, Jeremy D. Kark, Athanase Benetos, Christine Dalgård, Kent Horvath, Simon Verhulst, Masayuki Kimura, Kaare Christensen, Abraham Aviv, Verhulst lab, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de Gériatrie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), University of Southern Denmark (SDU), Hadassah School of Public Health and Community Medicine, The Hebrew University of Jerusalem (HUJ), University of Groningen [Groningen], Department of Clinical Biochemistry and Pharmacology, OdenseUniversity Hospital, Sdr. Boulevard 29, Center of Human Development and Aging, New Jersey Medical School, Rutgers New Jersey Medical School (NJMS), Rutgers University System (Rutgers)-Rutgers University System (Rutgers), Institute of Regional Health Services Research, Odense Patient Data Explorative Network (OPEN), and Odense University Hospital (OUH)
Subjects: Male, Aging, Epidemiology, Twins, Uterus, Female fetus, 0302 clinical medicine, Early Life Exposures, Leukocytes, Twins, Dizygotic, 0303 health sciences, education.field_of_study, Men, HUMANS, General Medicine, twins, Middle Aged, Telomere, REDUCE FITNESS, Blotting, Southern, medicine.anatomical_structure, Telomeres, In utero, Sex, Female, women, HEALTH, Sex characteristics, Adult, medicine.medical_specialty, TISSUES, Population, men, Biology, Dizygotic twins, 03 medical and health sciences, Sex Factors, AGE, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, sex, Women, education, 030304 developmental biology, Fetus, LIFE-COURSE, Twins, Monozygotic, Endocrinology, 030217 neurology & neurosurgery
Abstract: Background: In eutherian mammals and in humans, the female fetus may be masculinized while sharing the intra-uterine environment with a male fetus. Telomere length (TL), as expressed in leukocytes, is heritable and is longer in women than in men. The main determinant of leukocyte TL (LTL) is LTL at birth. However, LTL is modified by age-dependent attrition.Methods: We studied LTL dynamics (LTL and its attrition) in adult same-sex (monozygotic, n = 268; dizygotic, n = 308) twins and opposite-sex (n = 144) twins. LTL was measured by Southern blots of the terminal restriction fragments.Results: We observed that in same-sex (both monozygotic and dizygotic) twins, as reported in singletons, LTL was longer in females than in males [estimate +/- standard error (SE): 163 +/- 63 bp, PConclusions: These findings are compatible with masculinization of the female fetus in opposite-sex twins. They suggest that the sex difference in LTL, seen in the general population, is largely determined in utero, perhaps by the intrauterine hormonal environment. Further studies in newborn twins are warranted to test this thesis.
Published: 2014

44. Aluminium hydroxide-induced granulomas in pigs

Author: S. Valtulini, Martin Bak, A. Laval, C. Macchi, J. M. Theaker, E. Ferretti, Y. Cherel, P. Ballanti, H. Morvan, DVM Azienda Agricola Floria, Partenaires INRAE, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Développement et Pathologie du Tissu Musculaire (DPTM), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Nantes, Ecole Nationale Vétérinaire de Nantes, Southampton University Hospitals NHS Foundation Trust, Odense University Hospital (OUH), Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna 'Bruno Ubertini' (IZSLER), and Laboratoire de Développement et d'Analyses
Subjects: Veterinary medicine, Pathology, medicine.medical_specialty, Swine, GRANULOMA, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Aluminum Hydroxide, ADJUVANT, Necrosis, 030207 dermatology & venereal diseases, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Adjuvants, Immunologic, Skeletal pathology, medicine, Animals, Muscle, Skeletal, 030304 developmental biology, 0303 health sciences, Electron probe microanalysis, General Veterinary, General Immunology and Microbiology, business.industry, Inoculation, Spectrophotometry, Atomic, Aluminium hydroxide, Public Health, Environmental and Occupational Health, medicine.disease, 3. Good health, Infectious Diseases, chemistry, Granuloma, Molecular Medicine, business, Intramuscular injection, Adjuvant, Neck, ALUMINIUM HYDROXIDE, Aluminum, Electron Probe Microanalysis
Abstract: International audience; The effect of intramuscular injection of 40 mg/2 ml aluminium hydroxide in the neck of pigs was examined in a number of ways. The investigation followed repeated slaughterhouse reports, according to which 64.8% of pigs from one particular farm were found at slaughter to have one or more nodules in the muscles of the neck (group slaughtered). The pigs had been injected with a vaccine containing 40 mg/2 ml dose of aluminium hydroxide as adjuvant. Research consisted of two phases: first, an epidemiological study was carried out, aimed at determining the risk factors for the granulomas. The results indicated that the vaccine was to be held responsible for the formation of granulomas. A clinical trial was then performed to further substantiate the initial hypothesis, by comparing pigs, which were aseptically inoculated twice with either the original vaccine or the adjuvant alone (groups vaccine and adjuvant) to pigs inoculated twice with apyrogenic bi-distilled water (group water) and to pigs inoculated once with the adjuvant and once with apyrogenic bi-distilled water (group adjuvant/water). Both studies agreed in their conclusions, which indicate that the high amount of aluminium hydroxide was the cause of the granulomas.
Published: 2005

45. Genome-wide linkage analysis for human longevity: Genetics of Healthy Aging Study

Author: Beekman, M., Blanche, H., Perola, M., Hervonen, A., Bezrukov, V., Sikora, E., Flachsbart, F., Christiansen, L., Craen, A.J.M. de, Kirkwood, T.B.L., Rea, I.M., Poulain, M., Robine, J.M., Valensin, S., Stazi, M.A., Passarino, G., Deiana, L., Gonos, E.S., Paternoster, L., Sorensen, T.I.A., Tan, Q.H., Helmer, Q., Akker, E.B. van den, Deelen, J., Martella, F., Cordell, H.J., Ayers, K.L., Vaupel, J.W., Tornwall, O., Johnson, T.E., Schreiber, S., Lathrop, M., Skytthe, A., Westendorp, R.G.J., Christensen, K., Gampe, J., Nebel, A., Houwing-Duistermaat, J.J., Slagboom, P.E., Franceschi, C., GEHA Consortium, Leiden University Medical Center (LUMC), Fondation Jean Dausset - Centre d’Etudes du Polymorphisme Humain [Paris] (CEPH), National Institute for Health and Welfare [Helsinki], Tampere School of Public Health, Institute of Gerontology [Kiev], Nencki Institute of Experimental Biology, Polska Akademia Nauk = Polish Academy of Sciences (PAN), Christian-Albrechts University of Kiel, University of Southern Denmark (SDU), Netherlands Consortium for Healthy Ageing, Newcastle University [Newcastle], The Queen’s University of Belfast, Université Catholique de Louvain = Catholic University of Louvain (UCL), CERMES3 - Centre de recherche Médecine, sciences, santé, santé mentale, société (CERMES3 - UMR 8211 / U988 / UM 7), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-École des hautes études en sciences sociales (EHESS), University of Bologna, Istituto Superiore di Sanita [Rome], Università della Calabria [Arcavacata di Rende] (Unical), Università degli Studi di Sassari = University of Sassari [Sassari] (UNISS), Theoretical and Physical Chemistry Institute NHRF, National Hellenic Research Foundation, University of Bristol [Bristol], Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Odense University Hospital (OUH), Institute for Ageing and Health, Newcastle University, Max Planck Institute for Demographic Research (MPIDR), Max-Planck-Gesellschaft, University of Colorado [Boulder], Leiden University Medical Centre [Leyde, Pays-Bas], Leiden University, Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands, Institute for Ageing and Health, École des hautes études en sciences sociales (EHESS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Sassari, Danish Aging Research Center, Institute of Public Health, and Institute for Behavioral Genetics
Subjects: Aging, Genetic Linkage, APOE gene, Genome-wide association study, Association analysis, Human familial longevity, [SHS]Humanities and Social Sciences, 0302 clinical medicine, Mitochondrial Precursor Protein Import Complex Proteins, Cluster Analysis, Nonagenarian sibling pairs, media_common, Aged, 80 and over, Genetics, 0303 health sciences, Longevity, Chromosome Mapping, Middle Aged, Europe, genome-wide linkage analysis, association analysis, nonagenarian sibling pairs, apoe gene, human familial longevity, congenital, hereditary, and neonatal diseases and abnormalities, media_common.quotation_subject, Locus (genetics), Biology, Article, 03 medical and health sciences, Apolipoproteins E, SDG 3 - Good Health and Well-being, Genetic linkage, Humans, Allele, Alleles, Aged, 030304 developmental biology, Genetic association, Chromosomes, Human, Pair 14, Apolipoprotein C-I, Genome, Human, Siblings, Membrane Transport Proteins, Cell Biology, Heritability, Apoe gene, Genetic Loci, Human genome, Lod Score, Chromosomes, Human, Pair 19, Genome-wide linkage analysis, 030217 neurology & neurosurgery, Chromosomes, Human, Pair 17, Genome-Wide Association Study
Abstract: Clear evidence exists for heritability of humanlongevity, and much interest is focused on identifying genes associated with longer lives. To identify such longevity alleles, we performed the largest genome-wide linkage scan thus far reported. Linkage analyses included 2118nonagenarian Caucasian sibling pairs that have been enrolled in 15 study centers of 11 European countries as part of the Genetics of Healthy Aging (GEHA) project. In the joint linkage analyses, we observed four regions that show linkage with longevity; chromosome 14q11.2 (LOD = 3.47), chromosome 17q12-q22 (LOD = 2.95), chromosome 19p13.3-p13.11 (LOD = 3.76), and chromosome 19q13.11-q13.32 (LOD = 3.57). To fine map these regions linked to longevity, we performed association analysis using GWAS data in a subgroup of 1228 unrelated nonagenarian and 1907 geographically matched controls. Using a fixed-effect meta-analysis approach, rs4420638 at the TOMM40/ APOE/APOC1 gene locus showed significant association with longevity (P-value = 9.6 × 10 -8). By combined modeling of linkage and association, we showed that association of longevity with APOEe4 and APOEe2 alleles explain the linkage at 19q13.11-q13.32 with P-value = 0.02 and P-value = 1.0 × 10 -5, respectively. In the largest linkage scan thus far performed for human familial longevity, we confirm that the APOE locus is a longevity gene and that additional longevity loci may be identified at 14q11.2, 17q12-q22, and 19p13.3-p13.11. As the latter linkage results are not explained by common variants, we suggest that rare variants play an important role in human familial longevity.
Published: 2013

46. Design, recruitment, logistics, and data management of the GEHA (Genetics of Healthy Ageing) project

Author: C. Gilbault, G. Pelicci, Marian Beekman, Axel Skytthe, Serena Dato, A. Skouteri, Konstantinos Voutetakis, Luca Deiana, Ciriaco Carru, Ewa Sikora, Claudio Franceschi, Friederike Flachsbart, Leena Peltonen, James W. Vaupel, P. Laiho, Joanna Collerton, V. Bezrukov, Stefan Schreiber, Michel Poulain, Karen Davies, Irene Maeve Rea, Mikko Hurme, Giuseppe Passarino, Federica Sevini, Katarzyna Broczek, Outi Törnwall, Antti Hervonen, Elisa Cevenini, Hélène Blanché, Bernard Jeune, Maria Scurti, Rodolfo Cotichini, Jean-Marie Robine, Erica Haimes, A.J.M. de Craen, Thomas B. L. Kirkwood, R. Masciulli, José Remacle, Lene Christiansen, Dorota Janiszewska, F. Balard, Almut Nebel, A. Leon, P.E. Slagboom, Lars Bolund, A. Marchisio, Liana Spazzafumo, Marja Jylhä, Virgilia Toccaceli, G. De Benedictis, Markus Perola, Olivier Toussaint, Jutta Gampe, M A Stazi, Silvana Valensin, Peter Kristensen, Kaare Christensen, Efstathios S. Gonos, University of Southern Denmark (SDU), University of Bologna/Università di Bologna, Laboratoire Lorrain de Sciences Sociales (2L2S), Université de Lorraine (UL), Institut National de la Santé et de la Recherche Médicale (INSERM), Netherlands Consortium for Healthy Ageing, Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden, Institute of Gerontology [Kiev], Fondation Jean Dausset - Centre d’Etudes du Polymorphisme Humain [Paris] (CEPH), Beijing Genomics Institute [Shenzhen] (BGI), Institute of Human Genetics [Aarhus], Nencki Institute of Experimental Biology, Polska Akademia Nauk = Polish Academy of Sciences (PAN), Medical University of Warsaw - Poland, Università degli Studi di Sassari = University of Sassari [Sassari] (UNISS), Odense University Hospital (OUH), Newcastle University [Newcastle], Istituto Superiore di Sanità (ISS), Universiteit Leiden, Università della Calabria [Arcavacata di Rende] (Unical), Institute of Clinical Molecular Biology, Kiel University, Max Planck Institute for Demographic Research (MPIDR), Max-Planck-Gesellschaft, Université Catholique de Louvain = Catholic University of Louvain (UCL), National Hellenic Research Foundation [Athens], Tampere School of Public Health, University of Tampere [Finland], University of Aarhus, The National Institute for Health and Welfare, National Institute for Health and Welfare [Helsinki], Research Innovation [Italy], IFOM Institute of Milan, Queen's University [Belfast] (QUB), Eppendorf Array Technologies, CERMES3 - Centre de recherche Médecine, sciences, santé, santé mentale, société (CERMES3 - UMR 8211 / U988 / UM 7), École des hautes études en sciences sociales (EHESS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Istituto Nazionale Ricovero e Cura Anziani, Université de Namur [Namur] (UNamur), European Project: 26813,GEHA, University of Bologna, Istituto Superiore di Sanita [Rome], University of Calabria, The Queen’s University of Belfast, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-École des hautes études en sciences sociales (EHESS), Skytthe A., Valensin S., Jeune B., Cevenini E., Balard F., Beekman M., Bezrukov V., Blanche H., Bolund L., Broczek K., Carru C., Christensen K., Christiansen L., Collerton J.C., Cotichini R., de Craen A.J., Dato S., Davies K., De Benedictis G., Deiana L., Flachsbart F., Gampe J., Gilbault C., Gonos E.S., Haimes E., Hervonen A., Hurme M.A., Janiszewska D., Jylha M., Kirkwood T.B., Kristensen P., Laiho P., Leon A., Marchisio A., Masciulli R., Nebel A., Passarino G., Pelicci G., Peltonen L., Perola M., Poulain M., Rea I.M., Remacle J., Robine J.M., Schreiber S., Scurti M., Sevini F., Sikora E., Skouteri A., Slagboom P.E., Spazzafumo L., Stazi M.A., Toccaceli V., Toussaint O., Tornwall O., Vaupel J.W., Voutetakis K., Franceschi C., GEHA consortium [Pini Elisa, Palmas Maria Giustina, Panourgia Maria Panagiota], balard, frédéric, and GEnetics for Healthy Aging - GEHA - 26813 - OLD
Subjects: Research design, Gerontology, Male, Questionnaires, Aging, Genetic Linkage, [SDV]Life Sciences [q-bio], Genome-wide association study, Biochemistry, Nonagenarian sib pairs, [SHS]Humanities and Social Sciences, 0302 clinical medicine, Endocrinology, Cognition, Surveys and Questionnaires, 80 and over, Medicine, ComputingMilieux_MISCELLANEOUS, media_common, Genetics, Aged, 80 and over, 0303 health sciences, Life style, Longevity, Middle Aged, HEALTHY AGING, [SDV] Life Sciences [q-bio], Europe, Research Design, Extreme longevity tracking, Female, [SHS] Humanities and Social Sciences, media_common.quotation_subject, Article, 03 medical and health sciences, Healthy ageing, Humans, Family, Molecular Biology, Life Style, 030304 developmental biology, Genetic association, Aged, nonagenarian sib pair, business.industry, Patient Selection, Cell Biology, Multicenter study, business, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: In 2004, the integrated European project GEHA (Genetics of Healthy Ageing) was initiated with the aim of identifying genes involved in healthy ageing and longevity. The first step in the project was the recruitment of more than 2500 pairs of siblings aged 90years or more together with one younger control person from 15 areas in 11 European countries through a coordinated and standardised effort. A biological sample, preferably a blood sample, was collected from each participant, and basic physical and cognitive measures were obtained together with information about health, life style, and family composition. From 2004 to 2008 a total of 2535 families comprising 5319 nonagenarian siblings were identified and included in the project. In addition, 2548 younger control persons aged 50-75years were recruited. A total of 2249 complete trios with blood samples from at least two old siblings and the younger control were formed and are available for genetic analyses (e.g. linkage studies and genome-wide association studies). Mortality follow-up improves the possibility of identifying families with the most extreme longevity phenotypes. With a mean follow-up time of 3.7years the number of families with all participating siblings aged 95years or more has increased by a factor of 5 to 750 families compared to when interviews were conducted. Thus, the GEHA project represents a unique source in the search for genes related to healthy ageing and longevity. In 2004, the integrated European project GEHA (Genetics of Healthy Ageing) was initiated with the aim of identifying genes involved in healthy ageing and longevity. The first step in the project was the recruitment of more than 2500 pairs of siblings aged 90years or more together with one younger control person from 15 areas in 11 European countries through a coordinated and standardised effort. A biological sample, preferably a blood sample, was collected from each participant, and basic physical and cognitive measures were obtained together with information about health, life style, and family composition. From 2004 to 2008 a total of 2535 families comprising 5319 nonagenarian siblings were identified and included in the project. In addition, 2548 younger control persons aged 50-75years were recruited. A total of 2249 complete trios with blood samples from at least two old siblings and the younger control were formed and are available for genetic analyses (e.g. linkage studies and genome-wide association studies). Mortality follow-up improves the possibility of identifying families with the most extreme longevity phenotypes. With a mean follow-up time of 3.7years the number of families with all participating siblings aged 95years or more has increased by a factor of 5 to 750 families compared to when interviews were conducted. Thus, the GEHA project represents a unique source in the search for genes related to healthy ageing and longevity.
Published: 2011

47. Mixture Risk Assessment of Complex Real-Life Mixtures—The PANORAMIX Project

Author: Beate I. Escher, Marja Lamoree, Jean-Philippe Antignac, Martin Scholze, Matthias Herzler, Timo Hamers, Tina Kold Jensen, Marc Audebert, Francois Busquet, Dieter Maier, Michael Oelgeschläger, Maria João Valente, Henriette Boye, Sebastian Schmeisser, Gaud Dervilly, Matteo Piumatti, Soléne Motteau, Maria König, Kostja Renko, Maria Margalef, Ronan Cariou, Yanying Ma, Andreas Frederik Treschow, Andreas Kortenkamp, Anne Marie Vinggaard, E&H: Environmental Chemistry and Toxicology, AIMMS, E&H: Environmental Health and Toxicology, Helmholtz Zentrum für Umweltforschung = Helmholtz Centre for Environmental Research (UFZ), Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Vrije Universiteit Amsterdam [Amsterdam] (VU), Laboratoire d'étude des Résidus et Contaminants dans les Aliments (LABERCA), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Brunel University London [Uxbridge], German Federal Institute for Risk Assessment [Berlin] (BfR), University of Southern Denmark (SDU), Métabolisme et Xénobiotiques (ToxAlim-MeX), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), PrediTox, Altertox Academy, Biomax Informatics [Planegg], National Food Institute [Kongens Lyngby, Danemark], Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Odense University Hospital (OUH), The authors thank the European Union’s Horizon 2020 research and innovation programme, the Green Deal project PANORAMIX Grant Agreement No. 101036631 for its financial support., and European Project: 653497,H2020,H2020-DS-2014-1,PANORAMIX(2015)
Subjects: reproductive toxicity, real-life mixtures, effect-based trigger values, Health, Toxicology and Mutagenesis, [SDV]Life Sciences [q-bio], Public Health, Environmental and Occupational Health, Complex Mixtures, PANORAMIX, Risk Assessment, effect-directed analysis, Newmethodological approaches, new methodological approaches, SDG 3 - Good Health and Well-being, mixture risk assessment, Humans, developmental neurotoxicity, European Union, Organic Chemicals, newmethodological approaches, Environmental Pollution
Abstract: Copyright: © 2022 by the authors. Humans are involuntarily exposed to hundreds of chemicals that either contaminate our environment and food or are added intentionally to our daily products. These complex mixtures of chemicals may pose a risk to human health. One of the goals of the European Union’s Green Deal and zero-pollution ambition for a toxic-free environment is to tackle the existent gaps in chemical mixture risk assessment by providing scientific grounds that support the implementation of adequate regulatory measures within the EU. We suggest dealing with this challenge by: (1) characterising ‘real-life’ chemical mixtures and determining to what extent they are transferred from the environment to humans via food and water, and from the mother to the foetus; (2) establishing a high-throughput whole-mixture-based in vitro strategy for screening of real-life complex mixtures of organic chemicals extracted from humans using integrated chemical profiling (suspect screening) together with effect-directed analysis; (3) evaluating which human blood levels of chemical mixtures might be of concern for children’s development; and (4) developing a web-based, ready-to-use interface that integrates hazard and exposure data to enable component-based mixture risk estimation. These concepts form the basis of the Green Deal project PANORAMIX, whose ultimate goal is to progress mixture risk assessment of chemicals. Horizon 2020 research and innovation programme, the Green Deal project PANORAMIX Grant Agreement No. 101036631
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48. Impact of multidisciplinary team discrepancies on comparative lung cancer outcome analyses and treatment equality.

Author: Rasmussen TR, Gouliaev A, Jakobsen E, Hjorthaug K, Larsen LU, Meldgaard P, Thygesen J, Bibi R, Møller LB, Arshad A, Folkersen B, Højsgaard A, Saghir Z, Larsen KR, and Ravn J
Subjects: Humans, Denmark, Male, Female, Outcome Assessment, Health Care methods, Middle Aged, Aged, Treatment Outcome, Lung Neoplasms therapy, Lung Neoplasms pathology, Patient Care Team, Neoplasm Staging
Abstract: Introduction: This study aimed to evaluate the consistency of lung cancer case assessments across multidisciplinary team (MDT) sites in Denmark. The goal was to appraise the comparability of outcomes between hospitals in a real-world context., Methods: We prepared sixty comprehensive, fictitious lung cancer case stories, complete with images, and distributed them to the four primary lung cancer MDT conferences in Denmark. These cases were subsequently evaluated as had they been ordinary patients during regular MDT meetings. We compared the conclusions on assigned TNM stage and proposed treatment intent using Kappa statistics., Results: The consensus on assigned stage (Stages IA-B, IIA-B, IIIA-B, IV, and undetermined) corresponded to a Fleiss' Kappa-value of 0.62 (95% CI: 0.52-0.71). The overall assessment of curability, categorized as Curable, Incurable, and Undetermined, corresponded to a Kappa-value of 0.72 (CI: 0.61-0.84). However, for cases unanimously judged by all MDT sites to be Stage III, the concordance on treatment intent was poor, with an agreement coefficient of only 0.32 (95% CI: -0.27-0.97)., Conclusion: In detail, the level of agreement on assigned stages was less than desired. In consequence, comparative analyses of treatment results from different hospitals or centres may be prone to bias caused by systematic differences in stage assessment or intent of treatment. The least consensus was observed for cases in Stage III, indicating a need for quality improvement efforts to ensure a higher degree of consistency in MDT decisions., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. The study is based on fictitious case stories and associated imaging used in the study are fully and irrevocably anonymized. The Danish National Medical Research Ethics Committee (https://researchethics.dk/) waived the need for ethical approval and referred to the local Institutional Review Board at Aarhus University Hospital (IRB-AUH) for permission to access selected imaging for full and irrevocable anonymization and subsequent use in the study, for which permission was granted. The need for consent to participate was waived by IRB-AUH as it was deemed unnecessary for the intended use according to Danish national regulations (Danish Health Act, § 42 d (https://www.retsinformation.dk/eli/lta/2018/1286#P42d)). The use of fictitious case stories and fully and irrevocable anonymized data for research are permissible under Danish and European General Data Protection Regulation (the GPDR rules – REGULATION (EU) 2016/679 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 27 April 2016, article 26 (https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32016R0679)). Consent for publication Not applicable. The study is based on fictitious case stories and fully and irrevocably anonymized images, the use of which is permissible under Danish and European GDPR rules as stated and explained above for ‘Ethics approval and consent to participate’. Competing interests The authors declare no competing interests. Authors information Each author is a senior consultant with extensive experience in lung cancer diagnostics at university hospitals or is conducting research into the function of MDT in lung cancer., (© 2024. The Author(s).)
Published: 2024
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49. Neurocognitive deficits after botulism: a clinical case series study.

Author: Rosenqvist L, Sandvei C, and Skarphedinsson S
Abstract: Purpose: This case study examined long-term cognitive deficits after botulism. Only a very limited number of studies on post-acute cognitive impairment after botulism exist, and data are incomplete., Method: A semi-structured interview on long-term cognitive consequences of botulism was conducted for six family members, who contracted the infection after ingestion of lumpfish-roe 2.5 years ago. Two of the family members underwent neuropsychological assessment of attention, memory, and executive functioning as well., Finding: Results of the semi-structured interviews showed individual subjective cognitive deficits across processing speed, attention, concentration, short-and long-term memory, and executive functioning. Test results showed mild cognitive impairment in attention and mild-moderate deficits in executive functioning., Conclusion: These results support previous findings that patients of various infectious diseases may suffer unspecific long-term neurocognitive deficits. Assessment and initiation of relevant post-acute treatment and rehabilitation might be central to prognosis, functional ability, and psychological well-being., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Rosenqvist, Sandvei and Skarphedinsson.)
Published: 2024
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50. A Single Injection of ADRCs Does Not Prevent AAA Formation in Rats in a Randomized Blinded Design.

Author: Kavaliunaite E, Dhumale P, Jensen CH, Sheikh SP, Lindholt JS, and Stubbe J
Subjects: Animals, Rats, Male, Disease Models, Animal, Mesenchymal Stem Cells, Mesenchymal Stem Cell Transplantation methods, Aorta, Abdominal pathology, Aortic Aneurysm, Abdominal pathology, Aortic Aneurysm, Abdominal prevention & control, Aortic Aneurysm, Abdominal metabolism, Rats, Sprague-Dawley, Adipose Tissue
Abstract: There is a pressing need for alternative medical treatments for abdominal aortic aneurysms (AAAs). Mesenchymal regenerative cells derived from adipose tissue (ADRCs) have shown potential in modulating the inflammation and immune responses that drive AAA progression. We hypothesized that ADRCs could reduce inflammation and preserve vascular integrity, potentially slowing the progression of AAA. In our study, subcutaneous adipose tissue was harvested from male Sprague Dawley rats, from which ADRCs were isolated. AAA was induced in these rats using intraluminal porcine pancreatic elastase, followed by intravenous administration of either ADRCs (10 6 cells) or saline (0.1 mL). We monitored the progression of AAA through weekly ultrasound, and the rats were sacrificed on day 28 for histological analysis. Our results showed no significant difference in the inner abdominal aortic diameter at day 28 between the control group (172% ± 73%, n = 17) and the ADRC-treated group (181% ± 75%, n = 15). Histological analyses of AAA cross-sections also revealed no significant difference in the infiltration of neutrophils or macrophages between the two groups. Furthermore, the integrity and content of elastin in the tunica media were similar between groups. These findings indicate that a single injection of ADRCs does not inhibit the development of AAA in rats in a randomized blinded study.
Published: 2024
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