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1. Management goals for type 1 Gaucher disease: An expert consensus document from the European working group on Gaucher disease

Author: M. Weisz Hubshman, C.E.M. Hollak, Marc G. Berger, Theodore Marinakis, Fiorina Giona, Ursula Plöckinger, Hanna Rosenbaum, Marieke Biegstraaten, Gregory M. Pastores, J. Timmerman, Tanya Collin-Histed, Eugen Mengel, Dimitrios I. Zafeiriou, Cristina Fraga, M. Di Rocco, Ari Zimran, Nadia Belmatoug, Per Ole Iversen, Argiris Symeonidis, Derralynn Hughes, Anna Tylki-Szymańska, Elena Lukina, Jeff Szer, S. vom Dahl, M. Hasanhodzic, P Giraldo, Timothy M. Cox, Christine Serratrice, A.I. Kiewiet, Maciej Machaczka, Other departments, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Department of Surgical Oncology, Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed)-Humanitas University [Milan] (Hunimed), University of KwaZulu-Natal [Durban, Afrique du Sud] (UKZN), Department of Endocrinology and Metabolism, University of Amsterdam [Amsterdam] (UvA), and University of KwaZulu-Natal (UKZN)
Subjects: 0301 basic medicine, medicine.medical_specialty, Consensus, Delphi study, Gaucher disease, Management goals, PROMs, Therapy, Delphi method, Early detection, Disease, 03 medical and health sciences, 0302 clinical medicine, Quality of life (healthcare), Humans, Medicine, Intensive care medicine, Set (psychology), Molecular Biology, ComputingMilieux_MISCELLANEOUS, business.industry, Disease Management, Type 1 Gaucher Disease, Expert consensus, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Cell Biology, Hematology, Social engagement, 3. Good health, Europe, 030104 developmental biology, 030220 oncology & carcinogenesis, Quality of Life, Physical therapy, Molecular Medicine, business
Abstract: Gaucher Disease type 1 (GD1) is a lysosomal disorder that affects many systems. Therapy improves the principal manifestations of the condition and, as a consequence, many patients show a modified phenotype which reflects manifestations of their disease that are refractory to treatment. More generally, it is increasingly recognised that information as to how a patient feels and functions [obtained by patient- reported outcome measurements (PROMs)] is critical to any comprehensive evaluation of treatment. A new set of management goals for GD1 in which both trends are reflected is needed. To this end, a modified Delphi procedure among 25 experts was performed. Based on a literature review and with input from patients, 65 potential goals were formulated as statements. Consensus was considered to be reached when >= 75% of the participants agreed to include that specific statement in the management goals. There was agreement on 42 statements. In addition to the traditional goals concerning haematological, visceral and bone manifestations, improvement in quality of life, fatigue and social participation, as well as early detection of long-term complications or associated diseases were included. When applying this set of goals in medical practice, the clinical status of the individual patient should be taken into account. (C) 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
Published: 2018
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2. Preoperative Magnetic Resonance Enterography in Predicting Findings and Optimizing Surgical Approach in Crohn's Disease

Author: Piero Bazzi, Matteo Sacchi, Laurent Peyrin-Biroulet, Cristiana Bonifacio, Marco Montorsi, Gionata Fiorino, Silvio Danese, Alberto Malesci, Sarah De Bastiani, Luca Balzarini, Antonino Spinelli, Department of Medical Biotechnologies and Translational Medicine [Milan], Università degli Studi di Milano [Milano] (UNIMI), Department of Surgical Oncology, Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed)-Humanitas University [Milan] (Hunimed), Division of Gastroenterology, Department of Radiology [Humanitas Research Hospital], Humanitas Research Hospital, Department of Gastroenterology [Humanitas Research Hospital], Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Spinelli, A., Fiorino, G., Bazzi, P., Sacchi, M., Bonifacio, C., De Bastiani, S., Malesci, A., Balzarini, L., Peyrin Biroulet, L., Montorsi, M., and Danese, S.
Subjects: Adult, Male, medicine.medical_specialty, Abdominal Abscess, Adolescent, [SDV]Life Sciences [q-bio], laparoscopy, Constriction, Pathologic, Disease, Surgical planning, Preoperative care, Patient Care Planning, surgery, Young Adult, Crohn Disease, Predictive Value of Tests, Preoperative Care, Intestinal Fistula, medicine, magnetic resonance imaging, Humans, Prospective Studies, Laparoscopy, Prospective cohort study, Crohn's disease, magnetic resonance enterography, medicine.diagnostic_test, business.industry, Gastroenterology, Magnetic resonance imaging, medicine.disease, Conversion to Open Surgery, Magnetic Resonance Imaging, digestive system diseases, 3. Good health, Surgery, Intestines, Predictive value of tests, Female, Radiology, business, Intestinal Obstruction
Abstract: International audience; BACKGROUND:Many Crohn's disease patients require surgery. Intraoperative detection of new lesions may lead to change in planned surgery. This study aimed to determine whether magnetic resonance enterography can optimize surgical planning and guide decision making in Crohn's disease.METHODS:Seventy-five patients with complicated Crohn's disease were enrolled and underwent preoperative magnetic resonance enterography. Analysis included imaging accuracy and change in surgical strategy due to discordance with imaging findings.RESULTS:Surgery was performed laparoscopically in 39/75 patients (52 %), with conversion to open surgery required in six (15 %). Concordance between observers was excellent (kappa value >0.8). Magnetic resonance enterography accuracy for stenosis, abscess, and fistula were all above 85 % in per-patient analysis. In 68/75 cases (90.7 %) surgery was correctly predicted. Conversely, in 7/75 cases (three false-positives and four false-negatives) surgical strategy (type of resection or strictureplasty, n = 5) and/or surgical approach (conversion from laparoscopy to open surgery, n = 2) changed due to discordance with magnetic resonance enterography findings.CONCLUSION:Surgical strategy and approach are correctly predicted by magnetic resonance enterography in the majority of patients with complicated Crohn's disease.
Published: 2013
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3. Efficacy of adalimumab in patients with Crohn's disease and symptomatic small bowel stricture: a multicentre, prospective, observational cohort (CREOLE) study

Author: David Laharie, Gilles Bommelaer, Carmen Stefanescu, Silvio Danese, Jacques Moreau, Matthieu Allez, Stéphane Nancey, Romain Altwegg, Anne Bourrier, Jean-Yves Mary, Xavier Roblin, Vered Abitbol, Laurence Picon, Yoram Bouhnik, Guillaume Savoye, Xavier Hébuterne, Laurent Peyrin-Biroulet, Guillaume Bouguen, Edouard Louis, Franck Carbonnel, Magaly Zappa, Maria Nachury, Hedia Brixi, Mathurin Fumery, Arnaud Bourreille, Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon, Service d'hépato-gastro-entérologie, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Département d'hépatologie et de gastroentérologie, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service de gastro-entérologie et nutrition clinique, Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital l'Archet, Service de Gastro-entérologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Service des Maladies de l'Appareil Digestif et de la Nutrition [CHRU Lille], Fédération Hospitalière de France-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Hôpital Claude Huriez [Lille], Service d'hépato-gastro-entérologie et cancérologie digestive [CHU de Reims], Centre Hospitalier Universitaire de Reims (CHU Reims), Service d'hépato-gastro-entérologie, cancérologie digestive et assistance nutritionnelle [CHU de Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Hépato-Gastro-Onco-Entérologie [CHRU de Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Service de Gastroentérologie et nutrition [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Gastro-entérologie et Nutrition[Rangueil], CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Service d'Hépato-Gastroentérologie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Autophagie infections immunité – Autophagy Infection Immunity, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service de gastroentérologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Hépato-gastro-entérologie, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service des Maladies de l'Appareil Digestif, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Département d'Hépato-Gastroentérologie, Hôtel-Dieu-CHU Clermont-Ferrand-Université de Clermont-Ferrand, Gastroenterology, Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed)-Humanitas University [Milan] (Hunimed), Université de Liège, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Fédération Hospitalière de France-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service d'Hépato-Gastroentérologie [CHU Rouen], Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Autophagie infection et immunité - Autophagy Infection Immunity (APY), 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), OUERTANI, jeannette, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Pôle Maladies de l'appareil digestif [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service des Maladies de l'Appareil Digestif [CHU Rennes], CHU Pontchaillou [Rennes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Gastro-entérologie et Hépatologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Bouhnik, Y, Carbonnel, F, Laharie, D, Stefanescu, C, Hebuterne, X, Abitbol, V, Nachury, M, Brixi, H, Bourreille, A, Picon, L, Bourrier, A, Allez, M, Peyrin-Biroulet, L, Moreau, J, Savoye, G, Fumery, M, Nancey, S, Roblin, X, Altwegg, R, Bouguen, G, Bommelaer, G, Danese, S, Louis, E, Mary, Jy, Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), CHU Lille-CHU Lille, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: medicine.medical_specialty, medicine.medical_treatment, CROHN'S DISEASE, Disease, 03 medical and health sciences, 0302 clinical medicine, Clinical endpoint, Adalimumab, Medicine, IBD CLINICAL, Crohn's disease, business.industry, Inflammatory Bowel Disease, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Bowel resection, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, Surgery, 030220 oncology & carcinogenesis, Cohort, ABDOMINAL MRI, 030211 gastroenterology & hepatology, Observational study, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, business, Cohort study, medicine.drug
Abstract: ObjectiveThe efficacy of anti-tumour necrosis factors (anti-TNFs) in patients with Crohn's disease (CD) and symptomatic small bowel stricture (SSBS) is controversial. The aim of this study was to estimate the efficacy of adalimumab in these patients and to identify the factors predicting success.DesignWe performed a multicentre, prospective, observational cohort study in patients with CD and SSBS. The included patients underwent magnetic resonance enterography at baseline and subsequently received adalimumab. The primary endpoint was success at week 24, defined as adalimumab continuation without prohibited treatment (corticosteroids after the eight week following inclusion, other anti-TNFs), endoscopic dilation or bowel resection. The baseline factors independently associated with success were identified using a logistic regression model, leading to a simple prognostic score. Secondary endpoints were prolonged success after week 24 (still on adalimumab, without dilation nor surgery) and time to bowel resection in the whole cohort.ResultsFrom January 2010 to December 2011, 105 patients were screened and 97 were included. At week 24, 62/97 (64%) patients had achieved success. The prognostic score defined a good prognosis group with 43/49 successes, an intermediate prognosis group with 17/28 successes and a poor prognosis group with 1/16 successes. After a median follow-up time of 3.8 years, 45.7%±6.6% (proportion±SE) of patients who were in success at week 24 (ie, 29% of the whole cohort) were still in prolonged success at 4 years. Among the whole cohort, 50.7%±5.3% of patients did not undergo bowel resection 4 years after inclusion.ConclusionsA successful response to adalimumab was observed in about two-thirds of CD patients with SSBS and was prolonged in nearly half of them till the end of follow-up. More than half of the patients were free of surgery 4 years after treatment initiation.Clinical Trial registration numberNCT01183403; Results.
Published: 2017
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4. Development and validation of the Nancy histological index for UC

Author: Stefan Schreiber, Laurent Peyrin-Biroulet, Guillaume Cadiot, Virginie Cahn, Simon Travis, Silvio Danese, Aude Marchal-Bressenot, Walter Reinisch, Marie-Danièle Diebold, Claire Bastien, Julia Salleron, Camille Boulagnon-Rombi, Service de Pathologie [CHU Reims], Centre Hospitalier Universitaire de Reims (CHU Reims), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Département de biostatistiques [ICL Alexis Vautrin], Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER-UNICANCER, Service de Pathologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Département de Pathologie [Centre Hospitalier Sud Francilien], Centre Hospitalier Sud Francilien, CH Evry-Corbeil-CH Evry-Corbeil, Service d'hépato-gastroentérologie (CHU Reims), Gastroenterology [Istituto Clinico Humanitas], Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed)-Humanitas University [Milan] (Hunimed), University Medical Center of Schleswig–Holstein = Universitätsklinikum Schleswig-Holstein (UKSH), Kiel University, Translational Gastroenterology Unit [Oxford University Hospitals], Oxford University Hospitals NHS Trust, University of Oxford [Oxford]-University of Oxford [Oxford], Service d'Hépato-gastro-entérologie [CHRU Nancy], Marchal-Bressenot, A, Salleron, J, Boulagnon-Rombi, C, Bastien, C, Cahn, V, Cadiot, G, Diebold, Md, Danese, S, Reinisch, W, Schreiber, S, Travis, S, and Peyrin-Biroulet, L
Subjects: medicine.medical_specialty, Pathology, Coefficient of determination, Index (economics), Colon, Intraclass correlation, Biopsy, [SDV]Life Sciences [q-bio], Severity of Illness Index, Correlation, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Active disease, Linear regression, Severity of illness, medicine, Humans, Ulcerative Colitis, IBD CLINICAL, Observer Variation, medicine.diagnostic_test, business.industry, Gastroenterology, Reproducibility of Results, HISTOPATHOLOGY, PostScript, 030220 oncology & carcinogenesis, Linear Models, Colitis, Ulcerative, 030211 gastroenterology & hepatology, Mucosal Pathology, business, Algorithms
Abstract: Objective We developed a validated index for assessing histological disease activity in UC and established its responsiveness. Methods Two hundred biopsies were scored. The outcome was the Global Visual Evaluation (GVE). Eight histological features were tested. The Nancy index was developed by multiple linear regression and bootstrap process to create an index that best matched the GVE. Goodness of fit was assessed by the adjusted R squared (adjusted R-2). The second step was the validation of the index: 100 biopsies were scored for the Nancy index by three pathologists from different centres. Inter-reader reliability was evaluated for each reader. The relationship between the change of the Nancy index and the Geboes index was assessed to assess the responsiveness. Results After backward selection with bootstrap validation, 3/8 items were selected: ulceration (adjusted R-2=0.55), acute inflammatory infiltrate (adjusted R-2=0.88) and chronic inflammatory infiltrate (adjusted R-2=0.79). The Nancy index is defined by a 5-level classification ranging from grade 0 (absence of significant histological disease activity) to grade 4 (severely active disease). The intraclass correlation coefficient (ICC) for the intrareader reliability was 0.88 (95% CI 0.82 to 0.92) and the index had good interreader reliability (ICC=0.86 (0.81 to 0.99)). The correlation between the Nancy index and the Geboes score or the GVE was very good. The index had a good responsiveness with a high correlation between changes in the Geboes score and changes in the Nancy index (0.910 (0.813 to 0.955)). Conclusions A three descriptor histological index has been validated for use in clinical practice and clinical trials.
Published: 2016
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5. Beyond cortical localization in clinico-anatomical correlation

Author: Stephanie J. Forkel, Marco Catani, Andrew Simmons, Declan G. Murphy, Steve C.R. Williams, Michel Thiebaut de Schotten, Alberto Bizzi, Flavio Dell'Acqua, Natbrainlab, Department of Forensic and Neurodevelopmental Sciences, Institute of psychiatry-King‘s College London, Department of Neuroimaging, Neuroradiology Unit, Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed)-Humanitas University [Milan] (Hunimed), 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), and Thiebaut De Schotten, Michel
Subjects: Cognitive Neuroscience, Experimental and Cognitive Psychology, Brain mapping, 050105 experimental psychology, White matter, 03 medical and health sciences, Cognition, 0302 clinical medicine, Neural Pathways, Image Processing, Computer-Assisted, medicine, Humans, 0501 psychology and cognitive sciences, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Brain Mapping, 05 social sciences, Brain, Hyperintensity, Diffusion Tensor Imaging, Neuropsychology and Physiological Psychology, medicine.anatomical_structure, Group analysis, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Speech disorder, medicine.symptom, Psychology, Neuroscience, 030217 neurology & neurosurgery, Diffusion MRI, Tractography
Abstract: International audience; Last year was the 150th anniversary of Paul Broca's landmark case report on speech disorder that paved the way for subsequent studies of cortical localization of higher cognitive functions. However, many complex functions rely on the activity of distributed networks rather than single cortical areas. Hence, it is important to understand how brain regions are linked within large-scale networks and to map lesions onto connecting white matter tracts. To facilitate this network approach we provide a synopsis of classical neurological syndromes associated with frontal, parietal, occipital, temporal and limbic lesions. A review of tractography studies in a variety of neuropsychiatric disorders is also included. The synopsis is accompanied by a new atlas of the human white matter connections based on diffusion tensor tractography freely downloadable on http://www.natbrainlab.com. Clinicians can use the maps to accurately identify the tract affected by lesions visible on conventional CT or MRI. The atlas will also assist researchers to interpret their group analysis results. We hope that the synopsis and the atlas by allowing a precise localization of white matter lesions and associated symptoms will facilitate future work on the functional correlates of human neural networks as derived from the study of clinical populations. Our goal is to stimulate clinicians to develop a critical approach to clinico-anatomical correlative studies and broaden their view of clinical anatomy beyond the cortical surface in order to encompass the dysfunction related to connecting pathways.
Published: 2012
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6. Excess risk of urinary tract cancers in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study

Author: Bourrier, A., Carrat, F., Colombel, F., Bouvier, A., Abitbol, Vered, Marteau, P., Cosnes, J., Simon, T., Peyrin-Biroulet, Laurent, Beaugerie, L., Carbonnel, Franck, Colombel, Jean Frédéric, Filippi, Jérôme, Katsanos, Konstantinos, Allez, Mathieu, Nachury, Maria, Novacek, Gottfried, Danese, Silvio, Bossa, Fabrizio, Moreau, Jacques, Bommelaer, Gilles, Bourreille, Arnaud, Fumery, Mathurin, Roblin, Xavier, Reinisch, Walter, Bouhnik, Yoram, Brixi, Hedia, Seksik, Philippe, Malamut, Georgia, Färkkilä, Martti, Coulibaly, Baya, Dewit, Olivier, Louis, Edouard, Deplanque, Dominique, Michetti, Pierre, Sarter, Hélène, Laharie, David, Demolin, Julie, Détré, Patricia, Brillaut, Gaëlle, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire des biomolécules (LBM UMR 7203), Université Pierre et Marie Curie - Paris 6 (UPMC)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), ESIM - Déterminants Sociaux de la Santé et du Recours aux Soins (DS3), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Icahn School of Medicine at Mount Sinai [New York] (MSSM), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Université Paris Descartes - Paris 5 (UPD5), Service de Gastro-entérologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7), Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC), Centre de Ressources Biologiques HUEP-UPMC (CRB HUEP-UPMC), UMS omique (OMIQUE), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hépatogastroentérologie, CHU de Bicêtre, Centre d'Investigation Clinique Lille, PRES Université Lille Nord de France-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hépato-Gastroentérologie, Centre Hospitalier Universitaire de Nice (CHU Nice), University Hospital of Ioannina, Hôpital Saint-Louis, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Gastroenterology, Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed)-Humanitas University [Milan] (Hunimed), Service de Gastroentérologie et pancréatologie [CHU Toulouse], Pôle Maladies de l'appareil digestif [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut National de la Santé et de la Recherche Médicale (INSERM), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA), Neuropathies du système nerveux entérique et pathologies digestives, implication des cellules gliales entériques, Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Amiens-Picardie, Service de Gastro-entérologie et Hépatologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Clinic of Internal Medicine IV, Department of Gastroenterology and Hepathology, Universität Wien, Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Service de gastroenterologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université de Liège, CIC CHU ( Lille)/inserm, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Institut National de Veille Sanitaire, Institut national de veille sanitaire, Service d'Hépato-Gastro-Entérologie, CHU Bordeaux [Bordeaux]-Hôpital Saint-André, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Department of Gastroenterology, CHU Toulouse [Toulouse], Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Centre hospitalier universitaire d'Amiens (CHU Amiens-Picardie), Service de gastroentérologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Hôpital Beaujon, Service de Gastroentérologie et nutrition [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Laboratoire des technologies de la microélectronique (LTM), Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'Énergie Atomique et aux Énergies Alternatives (CEA) - Grenoble-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Epidémiologie, Systèmes dínformation et modélisation (ESIM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), CHU Saint-Antoine [APHP], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Université Pierre et Marie Curie - Paris 6 ( UPMC ), Département de santé publique, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Institut Pierre Louis d'Epidémiologie et de Santé Publique ( iPLESP ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Icahn School of Medicine at Mount Sinai [New York], Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Université Paris Descartes - Paris 5 ( UPD5 ), Département de gastroentérologie, CHU Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 ( UPD7 ), Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Nutrition-Génétique et Exposition aux Risques Environnementaux ( NGERE ), Université de Lorraine ( UL ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Tenon [APHP]-Assistance publique - Hôpitaux de Paris (AP-HP)-Université Pierre et Marie Curie - Paris 6 ( UPMC ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lorraine ( UL ), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Laboratoire des technologies de la microélectronique (LTM ), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), and Université Paris Diderot - Paris 7 (UPD7)-Hôpital Lariboisière-Fernand-Widal [APHP]
Subjects: Adult, Male, Nonmelanoma Skin Cancers, medicine.medical_specialty, Urologic Neoplasms, Urinary system, Gastroenterology, Cohort Studies, Association, 03 medical and health sciences, Young Adult, 0302 clinical medicine, [ CHIM.ORGA ] Chemical Sciences/Organic chemistry, Risk Factors, Internal medicine, Azathioprine, Medicine, Humans, Pharmacology (medical), Prospective Studies, Prospective cohort study, Proportional Hazards Models, Transplantation, Bladder cancer, Hepatology, business.industry, Incidence (epidemiology), Incidence, Hazard ratio, Malignancy, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Middle Aged, Metaanalysis, medicine.disease, Inflammatory Bowel Diseases, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, 030220 oncology & carcinogenesis, Cohort, 030211 gastroenterology & hepatology, Female, Therapy, business, Cohort study
Abstract: Background The risk of urinary tract cancers, including kidney and bladder cancers, was increased in transplant recipients receiving thiopurines. Aim To assess the risk of urinary tract cancers in patients with inflammatory bowel disease (IBD) receiving thiopurines in the CESAME observational cohort. Methods Between May 2004 and June 2005, 19 486 patients with IBD, 30.1% of whom were receiving thiopurines, were enrolled. Median follow-up was 35 months (IQR: 29-40). Results Ten and six patients developed respectively kidney and bladder cancer. The incidence rates of urinary tract cancer were 0.48/1000 patient-years in patients receiving thiopurines (95% CI: 0.21-0.95), 0.10/1000 patient-years in patients who discontinued thiopurines (95% CI: 0.00-0.56) and 0.30/1000 patient-years in patients never treated with thiopurines (95% CI: 0.12-0.62) at entry. The standardised incidence ratio of urinary tract cancer was 3.40 (95% CI: 1.47-6.71, P = 0.006) in patients receiving thiopurines, 0.64 (95% CI: 0.01-3.56, P = 0.92) in patients previously exposed to thiopurines and 1.17 (95% CI: 0.47-12.42, P = 0.78) in patients never treated with thiopurines. The multivariate-adjusted hazard ratio (HR) of urinary tract cancer between patients receiving thiopurines and those not receiving thiopurines was 2.82 (95% CI: 1.04-7.68, P = 0.04). Other significant risk factors were male gender (HR: 3.98, 95% CI: 1.12-14.10, P = 0.03) and increasing age (HR after 65 years (ref
Published: 2016
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7. Effectiveness of budesonide MMX (Cortiment) for the treatment of mild-to-moderate active ulcerative colitis: study protocol for a prospective multicentre observational cohort study

Author: Claudio Iannacone, Laurence D’Agay, Edouard Louis, Silvio Danese, Geert R. D'Haens, Iris Dotan, Laurent Peyrin-Biroulet, Axel Dignass, Gerhard Rogler, Ailsa Hart, Amsterdam Gastroenterology Endocrinology Metabolism, Gastroenterology and Hepatology, Danese, S, Hart, A, Dignass, A, Louis, E, D'Haens, G, Dotan, I, Rogler, G, D'Agay, L, Iannacone, C, Peyrin-Biroulet, L, University of Zurich, Danese, Silvio, Gastroenterology, Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed)-Humanitas University [Milan] (Hunimed), Humanitas University [Milan] (Hunimed), Northwick Park & St Marks Hospital, Department of Medicine I, Agaplesion Markus Krankenhaus = Agaplesion Markus Hospital [Frankfurt], Centre Hospitalier Universitaire de Liège (CHU-Liège), Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Tel Aviv Sourasky Medical Center [Te Aviv], University hospital of Zurich [Zurich], Ferring Pharmaceuticals A/S, McCann Complete Medical, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], and Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)
Subjects: Budesonide, medicine.medical_specialty, Efficacy, Remission, [SDV]Life Sciences [q-bio], 610 Medicine & health, Inflammatory bowel disease, Gastroenterology, Induction, Quality-Of-Life, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Mesalazine, Internal medicine, Diagnosis, medicine, IBD CLINICAL, 2715 Gastroenterology, Crohns-Disease, business.industry, Inflammatory Bowel Disease, 9 Mg, medicine.disease, Ulcerative colitis, Evidence-Based Consensus, Management, 3. Good health, 10219 Clinic for Gastroenterology and Hepatology, Tolerability, chemistry, ULCERATIVE COLITIS, 030220 oncology & carcinogenesis, Propensity score matching, 030211 gastroenterology & hepatology, business, Inflammatory-Bowel-Disease, medicine.drug, Cohort study, MMX
Abstract: Introduction A study has been developed to assess the use and effectiveness of budesonide MMX for mild-to-moderate active ulcerative colitis (UC) in routine clinical practice. Methods and analysis A prospective, multicentre, observational, cohort study of 300 patients prescribed budesonide MMX for the treatment of mild-to-moderate active UC will be conducted in Europe, Israel and Canada. Patients will be treated with budesonide MMX9 mg daily for induction of remission for ≤8 weeks. Data on effectiveness, including patient-reported outcomes, tolerability and use will be recorded at the end of treatment and at ≥2 weeks after. The primary outcome (improvement ≥3 point in the clinical subscores of the UC Disease Activity Index score at the end of treatment) will be compared in: patients who receive budesonide MMX added to mesalazine >2 weeks after increased/optimised mesalazine dose for the treatment of flare (late add-on); patients who receive budesonide MMX added to mesalazine ≤2 weeks since mesalazine increased/optimised for the treatment of flare, or without mesalazine dose modification (early add-on); and patients who receive budesonide MMX as monotherapy for the treatment of flare (mono). Propensity scoring will be used to minimise bias and confounding inherent in observational studies. Ethics and dissemination First ethical approval: Ethikkommission der Arztekammer Hamburg (12/22/2015). The results will be published in full. Discussion Completion of primary data collection is expected in December 2017. Our results will provide further evidence on the effectiveness of budesonide MMX to support clinicians in their daily practice and inform therapeutic guidelines. Trial registration number NCT02586259.
Published: 2016
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8. Development of Red Flags Index for Early Referral of Adults with Symptoms and Signs Suggestive of Crohn’s Disease: An IOIBD Initiative

Author: Severine Vermeire, Gionata Fiorino, Jean Yves Mary, Simon Travis, Laurent Peyrin-Biroulet, Jean-Frederic Colombel, André D'Hoore, Silvio Danese, Geert R. D'Haens, Julián Panés, Walter Reinisch, Lorenzo Moja, William J. Sandborn, Peter L. Lakatos, Gastroenterology, Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed)-Humanitas University [Milan] (Hunimed), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), Semmelweis University [Budapest], Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Istituto Ortopedico Galeazzi-IRCCS, Abdominal Surgery and Radiology University Hospital Leuven, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Liver Unit, Clínica Universitaria, CIBER-EHD, Medizinische Universität Wien = Medical University of Vienna, University of California [San Diego] (UC San Diego), University of California, John Radcliffe Hospital [Oxford University Hospital], Division of Gastroenterology [University Hospitals Leuven], University Hospitals Leuven [Leuven], Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Icahn Medical Institute-Mount Sinai School of Medicine, Department of Gene and Cell Medicine and Institute for Immunology, 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), AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Gastroenterology and Hepatology, Danese, S, Fiorino, G, Mary, Jy, Lakatos, Pl, D'Haens, G, Moja, L, D'Hoore, A, Panes, J, Reinisch, W, Sandborn, Wj, Travis, Sp, Vermeire, S, Peyrin-Biroulet, L, and Colombel, Jf
Subjects: Adult, Crohn’s disease, Pediatrics, medicine.medical_specialty, Delayed Diagnosis, Multivariate analysis, Red Flags, [SDV]Life Sciences [q-bio], Disease, Logistic regression, Risk Assessment, Sensitivity and Specificity, Decision Support Techniques, Crohn Disease, Surveys and Questionnaires, Health Status Indicators, Humans, Medicine, Referral and Consultation, Irritable bowel syndrome, Crohn's disease, Receiver operating characteristic, business.industry, Gastroenterology, General Medicine, Odds ratio, medicine.disease, diagnostic delay, Confidence interval, 3. Good health, Cross-Sectional Studies, Early Diagnosis, business
Abstract: International audience; BACKGROUND AND AIMS:Diagnostic delay is frequent in patients with Crohn's disease (CD). We developed a tool to predict early diagnosis.METHODS:A systematic literature review and 12 CD specialists identified 'Red Flags', i.e. symptoms or signs suggestive of CD. A 21-item questionnaire was administered to 36 healthy subjects, 80 patients with irritable bowel syndrome (non-CD group) and 85 patients with recently diagnosed (
Published: 2015
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9. State-of-the-art CT and MR imaging and assessment of atherosclerotic carotid artery disease

Author: Luca Saba, Christian Loewe, Thomas Weikert, Michelle C. Williams, Nicola Galea, Ricardo P. J. Budde, Rozemarijn Vliegenthart, Birgitta K. Velthuis, Marco Francone, Jens Bremerich, Luigi Natale, Konstantin Nikolaou, Jean-Nicolas Dacher, Charles Peebles, Federico Caobelli, Alban Redheuil, Marc Dewey, Karl-Friedrich Kreitner, Rodrigo Salgado, DACHER, Jean Nicolas, University of Cagliari, Medizinische Universität Wien = Medical University of Vienna, University of Basel (Unibas), University of Edinburgh, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Groningen [Groningen], University Medical Center [Utrecht], Humanitas University [Milan] (Hunimed), A. Gemelli Hospital [Rome, Italy], University of Tübingen, Nouvelles Cibles Pharmacologiques de la Protection Endothéliale et de l'Insuffisance Cardiaque (EnVI), CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU), University of Southampton, University of Bern, Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], University Medical Center [Mainz], Antwerp University Hospital [Edegem] (UZA), Radiology & Nuclear Medicine, Cardiovascular Centre (CVC), Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), and Digital Healthcare (DH)
Subjects: Atherosclerotic plaque, Consensus, carotid artery diseases, 610 Medicine & health, General Medicine, MR, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, CT angiography, consensus, Carotid artery diseases, Radiology, Nuclear Medicine and imaging, Human medicine
Abstract: Abstract The European Society of Cardiovascular Radiology (ESCR) is the European specialist society of cardiac and vascular imaging. This society’s highest priority is the continuous improvement, development, and standardization of education, training, and best medical practice, based on experience and evidence. The present intra-society consensus is based on the existing scientific evidence and on the individual experience of the members of the ESCR writing group on carotid diseases, the members of the ESCR guidelines committee, and the members of the executive committee of the ESCR. The recommendations published herein reflect the evidence-based society opinion of ESCR. We have produced a twin-papers consensus, indicated through the documents as respectively “Part I” and “Part II.” The first document (Part I) begins with a discussion of features, role, indications, and evidence for CT and MR imaging-based diagnosis of carotid artery disease for risk stratification and prediction of stroke (Section I). It then provides an extensive overview and insight into imaging-derived biomarkers and their potential use in risk stratification (Section II). Finally, detailed recommendations about optimized imaging technique and imaging strategies are summarized (Section III). The second part of this consensus paper (Part II) is focused on structured reporting of carotid imaging studies with CT/MR. Key Points • CT and MR imaging-based evaluation of carotid artery disease provides essential information for risk stratification and prediction of stroke. • Imaging-derived biomarkers and their potential use in risk stratification are evolving; their correct interpretation and use in clinical practice must be well-understood. • A correct imaging strategy and scan protocol will produce the best possible results for disease evaluation.
Published: 2023
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10. Role of alpha-synuclein in autophagy modulation of primary human T lymphocytes

Author: Elena Ortona, Carmelo Carlo-Stella, Tania Colasanti, Antonella Tinari, Loretta Tuosto, Fabrizio Conti, Cristina Camperio, Cristiano Alessandri, Walter Malorni, Marina Pierdominici, D Benincasa, Marta Vomero, Angela Maselli, Cristiana Barbati, Guido Valesini, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanita, Department of Medical Sciences, San Raffaele Institute Pisana, Department of Internal Medicine, Lupus Clinic, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], San Raffaele Institute Sulmona, Department of Biology and Biotechnology 'Charles Darwin', Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Department of Technology and Health, Istituto Superiore di Sanita [Rome], Department of Oncology and Hematology, Humanitas Cancer Center, Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed)-Humanitas University [Milan] (Hunimed), Department of Medical Biotechnology and Translational Medicine, CNR Neuroscience Institute-University of Milan, Laboratory of Clinical and Behavioral Neurology, Fondazione Santa Lucia (IRCCS), Movement Disorder Unit, Sant’Andrea Hospital, Department of Therapeutic Research and Medicine Evaluation, Istituto Superiore di Sanità, and This study was partially supported by grants from AIRC to WM (MCO – 9998 and 11505) and from the Italian Ministry of Health to EO (U7A).CC and LT are supported by Fondazione Italiana Sclerosi Multipla-FISM-Cod. 2011/R/36 (Genova, Italy).
Subjects: Male, Cancer Research, T-Lymphocytes, animal diseases, Pathogenesis, chemistry.chemical_compound, 0302 clinical medicine, systemic lupus erythematosus, Lupus Erythematosus, Systemic, MESH: Aged, 0303 health sciences, MESH: Middle Aged, Neurodegeneration, Middle Aged, 3. Good health, Gene Knockdown Techniques, alpha-Synuclein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Original Article, Female, Adult, autophagy, Programmed cell death, lymphoma, alpha-synuclein, t lymphocytes, Immunology, ATG5, T lymphocytes, Biology, 03 medical and health sciences, Cellular and Molecular Neuroscience, α-synuclein, mental disorders, MESH: alpha-Synuclein, medicine, Humans, MESH: Autophagy, MESH: Lupus Erythematosus, Systemic, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Aged, 030304 developmental biology, Alpha-synuclein, Lupus erythematosus, MESH: Humans, Autophagy, MESH: Biological Markers, MESH: Adult, Cell Biology, medicine.disease, MESH: Gene Knockdown Techniques, MESH: Male, nervous system diseases, MESH: T-Lymphocytes, chemistry, nervous system, Apoptosis, Cancer research, MESH: Female, Biomarkers, 030217 neurology & neurosurgery
Abstract: International audience; It has been demonstrated that α-synuclein can aggregate and contribute to the pathogenesis of some neurodegenerative diseases and it is capable of hindering autophagy in neuronal cells. Here, we investigated the implication of α-synuclein in the autophagy process in primary human T lymphocytes. We provide evidence that: (i) knocking down of the α-synuclein gene resulted in increased autophagy, (ii) autophagy induction by energy deprivation was associated with a significant decrease of α-synuclein levels, (iii) autophagy inhibition by 3-methyladenine or by ATG5 knocking down led to a significant increase of α-synuclein levels, and (iv) autophagy impairment, constitutive in T lymphocytes from patients with systemic lupus erythematosus, was associated with abnormal accumulation of α-synuclein aggregates. These results suggest that α-synuclein could be considered as an autophagy-related marker of peripheral blood lymphocytes, potentially suitable for use in the clinical practice.
Published: 2014
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11. Flow cytometric analysis of myelodysplasia: Pre-analytical and technical issues—Recommendations from the European LeukemiaNet

Author: Vincent H. J. van der Velden, Frank Preijers, Ulrika Johansson, Theresia M. Westers, Alan Dunlop, Anna Porwit, Marie C. Béné, Peter Valent, Jeroen te Marvelde, Orianne Wagner‐Ballon, Uta Oelschlaegel, Leonie Saft, Sharham Kordasti, Robin Ireland, Eline Cremers, Canan Alhan, Carolien Duetz, Willemijn Hobo, Nicolas Chapuis, Michaela Fontenay, Peter Bettelheim, Lisa Eidenshink‐Brodersen, Patricia Font, Michael R. Loken, Sergio Matarraz, Kiyoyuki Ogata, Alberto Orfao, Katherina Psarra, Dolores Subirá, Denise A. Wells, Matteo G. Della Porta, Kate Burbury, Frauke Bellos, Elisabeth Weiß, Wolfgang Kern, Arjan van de Loosdrecht, Hematology laboratory, Internal medicine, Hematology, VU University medical center, AII - Cancer immunology, CCA - Cancer biology and immunology, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Radboudumc Nijmegen [The Netherlands], University Hospitals Bristol, Amsterdam UMC - Amsterdam University Medical Center, Royal Marsden Hospital [Surrey, UK], Lund University [Lund], Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), 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)-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 hospitalier universitaire de Nantes (CHU Nantes), Medizinische Universität Wien = Medical University of Vienna, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Henri Mondor, University Hospital Carl Gustav Carus [Dresden, Germany], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Karolinska Institutet [Stockholm], King‘s College London, Maastricht University [Maastricht], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Ordensklinikum Linz Elisabethinen, HematoLogics, Inc. [Seattle, WA, USA], Hospital General Universitario 'Gregorio Marañón' [Madrid], Universidad de Salamanca, Instituto de Salud Carlos III [Madrid] (ISC), Metropolitan Research and Treatment Centre for Blood Disorders [Tokyo, Japan] (MRTC Japan), Evangelismos Athens General Hospital, Universidad de Guadalajara, Humanitas University [Milan] (Hunimed), University of Melbourne, Munich Leukemia Laboratory [Munich, Germany], MUMC+: MA Med Staf Artsass Interne Geneeskunde (9), RS: FHML non-thematic output, Immunology, and Bernardo, Elizabeth
Subjects: Histology, MASTOCYTOSIS, Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2], BONE-MARROW, DIAGNOSTIC-CRITERIA, [SDV.CAN]Life Sciences [q-bio]/Cancer, REFRACTORY CYTOPENIA, CLASSIFICATION, Pathology and Forensic Medicine, pre-analytic issues, 03 medical and health sciences, 0302 clinical medicine, All institutes and research themes of the Radboud University Medical Center, [SDV.CAN] Life Sciences [q-bio]/Cancer, SDG 3 - Good Health and Well-being, hemic and lymphatic diseases, MDS, 030304 developmental biology, 0303 health sciences, flow cytometry, Cell Biology, QUANTIFICATION, LOW-GRADE, 3. Good health, CONSENSUS STATEMENTS, ELN, 030215 immunology, STANDARDS
Abstract: Contains fulltext : 290818.pdf (Publisher’s version ) (Open Access) BACKGROUND: Flow cytometry (FCM) aids the diagnosis and prognostic stratification of patients with suspected or confirmed myelodysplastic syndrome (MDS). Over the past few years, significant progress has been made in the FCM field concerning technical issues (including software and hardware) and pre-analytical procedures. METHODS: Recommendations are made based on the data and expert discussions generated from 13 yearly meetings of the European LeukemiaNet international MDS Flow working group. RESULTS: We report here on the experiences and recommendations concerning (1) the optimal methods of sample processing and handling, (2) antibody panels and fluorochromes, and (3) current hardware technologies. CONCLUSIONS: These recommendations will support and facilitate the appropriate application of FCM assays in the diagnostic workup of MDS patients. Further standardization and harmonization will be required to integrate FCM in MDS diagnostic evaluations in daily practice. 01 januari 2023
Published: 2023
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12. Identification of the optimal medical and surgical management for patients with perianal fistulising Crohn’s disease

Author: Mathilde Laland, Marie François, Ferdinando D'Amico, Camille Zallot, Charlène Brochard, Marie Dewitte, Laurent Siproudhis, Laurent Peyrin‐Biroulet, Guillaume Bouguen, CHU Pontchaillou [Rennes], Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Humanitas University [Milan] (Hunimed), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Jonchère, Laurent
Subjects: [SDV] Life Sciences [q-bio], Crohn’s disease, medical and surgical management, [SDV]Life Sciences [q-bio], Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, perianal fistula, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, combination therapy
Abstract: International audience; AIMS: The aims of our study were to assess the best medical and surgical approaches for Perianal Crohn’s Disease (PCD) in order to identify an optimal combined medical and surgical treatment. METHODS: Medical records of all patients with PCD treated with TNFα antagonists in two referral centers between 1998 and 2018 were reviewed. Predictors of long-term outcomes were identified using a Cox proportional hazard model. RESULTS: A total of 200 patients were included. Fifty-three patients (26.5%) were treated with adalimumab and 147 (73.5%) with infliximab. Combination of TNFα antagonist with an immunosuppressant and presence of proctitis were independently associated with fistula closure. Seton was placed in 127 patients (63.5%) before starting biological therapy. Eighty patients (40%) underwent additional perineal surgery. Prior PCD surgery, seton positioning, additional perineal surgery, and additional surgery within 52 weeks of anti-TNFα treatment were associated with an increased rate of fistula closure. Finally, medical combination therapy (anti-TNFα plus immunosuppressant) along with seton placement and additional surgery within one year was the best management for PCD patients (p=0,02). CONCLUSION: Combined medical and surgical management is required for the treatment of PCD patients. Medical combination therapy associated with seton placement and additional surgery within one year is the best management for PCD patients.
Published: 2023
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13. Clinical application of flow cytometry in patients with unexplained cytopenia and suspected myelodysplastic syndrome: A report of the European LeukemiaNet International MDS-Flow Cytometry Working Group

Author: Loosdrecht, Arjan, Kern, Wolfgang, Porwit, Anna, Valent, Peter, Kordasti, Sharham, Cremers, Eline, Alhan, Canan, Duetz, Carolien, Dunlop, Alan, Hobo, Willemijn, Preijers, Frank, Wagner‐ballon, Orianne, Chapuis, Nicolas, Fontenay, Michaela, Bettelheim, Peter, Eidenschink‐brodersen, Lisa, Font, Patricia, Johansson, Ulrika, Loken, Michael, Marvelde, Jeroen, Matarraz, Sergio, Ogata, Kiyoyuki, Oelschlaegel, Uta, Orfao, Alberto, Psarra, Katherina, Subirá, Dolores, Wells, Denise, Béné, Marie, Della Porta, Matteo, Burbury, Kate, Bellos, Frauke, Velden, Vincent, Westers, Theresia, Saft, Leonie, Ireland, Robin, MUMC+: MA Med Staf Artsass Interne Geneeskunde (9), RS: FHML non-thematic output, Amsterdam UMC - Amsterdam University Medical Center, Munich Leukemia Laboratory [Munich, Germany] (M2L), Lund University [Lund], Medizinische Universität Wien = Medical University of Vienna, King‘s College London, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], The Royal Marsden, Radboud University Medical Center [Nijmegen], Hôpital Henri Mondor, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Ordensklinikum Linz Elisabethinen, HematoLogics, Inc. [Seattle, WA, USA], Hospital General Universitario 'Gregorio Marañón' [Madrid], University Hospitals Bristol, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Universidad de Salamanca, Metropolitan Research and Treatment Centre for Blood Disorders [Tokyo, Japan] (MRTC Japan), University Hospital Carl Gustav Carus [Dresden, Germany], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Evangelismos Athens General Hospital, Universidad de Guadalajara, Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), 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)-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 hospitalier universitaire de Nantes (CHU Nantes), Humanitas University [Milan] (Hunimed), Istituto Clinico Humanitas [Milan] (IRCCS Milan), University of Melbourne, Karolinska Institutet [Stockholm], King's College Hospital (KCH), Hematology, CCA - Cancer biology and immunology, Internal medicine, Hematology laboratory, Immunology, and Bernardo, Elizabeth
Subjects: standardization, Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2], flow cytometry, CONSORTIUM, [SDV.CAN]Life Sciences [q-bio]/Cancer, PROGNOSTIC SCORING SYSTEM, DIAGNOSIS, CYTOGENETICS, myelodysplastic syndromes, CLASSIFICATION, VALIDATION, All institutes and research themes of the Radboud University Medical Center, [SDV.CAN] Life Sciences [q-bio]/Cancer, consensus, hemic and lymphatic diseases, CELLS, SUBGROUPS, ELN, CYTOMORPHOLOGY
Abstract: Contains fulltext : 290800.pdf (Publisher’s version ) (Open Access) This article discusses the rationale for inclusion of flow cytometry (FCM) in the diagnostic investigation and evaluation of cytopenias of uncertain origin and suspected myelodysplastic syndromes (MDS) by the European LeukemiaNet international MDS Flow Working Group (ELN iMDS Flow WG). The WHO 2016 classification recognizes that FCM contributes to the diagnosis of MDS and may be useful for prognostication, prediction, and evaluation of response to therapy and follow-up of MDS patients. 01 januari 2023
Published: 2023
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14. Still a long way to go to achieve multidisciplinarity for the benefit of patients: commentary on the ESMO position paper (Annals of Oncology 25(1): 9-15, 2014)

Author: Alain Astier, A Torresin, Lorenzo Bonomo, Rolf-Dieter Kortmann, J F Verzijlbergen, Tiina Saarto, J G Eriksen, P.M. Poortmans, Barry D. Bultz, Luigi Grassi, Alessandro Brunelli, Per-Anders Abrahamsson, A Plate, W.H. van Harten, Sanchia Aranda, Graeme J. Poston, Mathieu Boniol, Mary Gospodarowicz, T Kutluk, C von Kalle, F. De Lorenzo, Riccardo A. Audisio, Vincenzo Valentini, Vicky Goh, Riccardo Soffietti, Joan Kelly, Arturo Chiti, Radiation Oncology Department, Catholic University of the Sacred Heart, Department of Urology, Skåne University Hospital, Melbourne School of Health Sciences [Melbourne], Faculty of Medicine, Dentistry and Health Sciences [Melbourne], University of Melbourne-University of Melbourne, Department of Pharmacy, Henri Mondor University Hospitals, Henri Mondor University Hospitals, University of Liverpool, International Prevention Research Institute (IPRI), Strathclyde Institute of Global Public Health at iPRI (SIGPH@iPRI), Department of Radiological Sciences, Catholic University of the Sacred Heart, Department of Thoracic Surgery, St. James’s University Hospital, Division of Psychosocial Oncology, Department of Oncology, University of Calgary, Department of Nuclear Medicine, Istituto Clinico Humanitas, Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed)-Humanitas University [Milan] (Hunimed), European Cancer Patient Coalition, Department of Oncology, Odense University Hospital, Institute of Clinical Research, University of Southern Denmark (SDU), Division of Imaging Sciences and Biomedical Engineering, St Thomas’ Hospital, University of Toronto, Princess Margaret Cancer Centre, Institute of Clinical Psychiatry, Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, Association of European Cancer Leagues, Department of Radiation Therapy, University of Leipzig, Department of Pediatric Oncology, Hacettepe University Cancer Institute, Myeloma Patients Europe, Cancer Center, Helsinki University Central Hospital, Department Neuro‐Oncology, University of Turin, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Netherlands Cancer Institute, Erasmus University Medical Center [Rotterdam] (Erasmus MC), National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), Radiation Oncology Department, Dr. B. Verbeeten Institute, Faculty of Behavioural, Management and Social Sciences, and Radiology & Nuclear Medicine
Subjects: Oncology, medicine.medical_specialty, psychosocial care, Best practice, Alternative medicine, MEDLINE, Medical Oncology, RS, RC0254, 03 medical and health sciences, 0302 clinical medicine, METIS-304637, Multidisciplinary approach, Neoplasms, Internal medicine, Humans Medical Oncology/*education Neoplasms/*therapy *Physician's Role, cancer, Humans, Physician's Role, Hematology, Medicine (all), Medicine, Settore MED/36 - DIAGNOSTICA PER IMMAGINI E RADIOTERAPIA, 030304 developmental biology, 0303 health sciences, IR-91529, business.industry, Neoplasms therapy, psychoncology, ESMO, 3. Good health, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], Multidisciplinarity, Annals, 030220 oncology & carcinogenesis, Position paper, Conviction, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: The paper by ESMO ‘The current and future role of the medical oncologist in the professional care for cancer patients: a position paper by the European Society for Medical Oncology (ESMO)’ [1] conveys some important key messages for the whole oncology community. A working group (WG) involving 21 oncology and related societies would like to comment on the paper from a multidisciplinary perspective in the conviction that a more transparent and open definition of individual professional roles better supports the patients' care and facilitates best practices and progress in comprehensive cancer care.
Published: 2014
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15. New mechanisms and targets for IBD Therapy: translational gastroenterology comes of age

Author: Silvio Danese, Peyrin-Biroulet, L., UL, NGERE, Gastroenterology, Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed)-Humanitas University [Milan] (Hunimed), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], and Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)
Subjects: Translational Research, Biomedical, [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], Age Factors, Cell- and Tissue-Based Therapy, Humans, Molecular Targeted Therapy, Inflammatory Bowel Diseases, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2013

16. International consensus on the prevention of venous and arterial thrombotic events in patients with inflammatory bowel disease

Author: Tim Raine, Siew C. Ng, Edouard Louis, David T. Rubin, Peter Bossuyt, Fernando Magro, Laurent Peyrin-Biroulet, Subrata Ghosh, Silvio Danese, Paulo Gustavo Kotze, Véronique Regnault, Fábio Vieira Teixeira, Patrick Lacolley, Alfredo Papa, Taku Kobayashi, Stéphane Zuily, Richard B. Gearry, Sameer Al Awadhi, Pablo Olivera, Zuily, Stephane [0000-0002-9326-6881], Kotze, Paulo G [0000-0002-9632-6691], Bossuyt, Peter [0000-0003-4027-7365], Ghosh, Subrata [0000-0002-1713-7797], Kobayashi, Taku [0000-0002-2073-4234], Ng, Siew C [0000-0002-6850-4454], Papa, Alfredo [0000-0002-4186-7298], Raine, Tim [0000-0002-5855-9873], Rubin, David T [0000-0001-5647-1723], Danese, Silvio [0000-0001-7341-1351], Peyrin-Biroulet, Laurent [0000-0003-2536-6618], Apollo - University of Cambridge Repository, Centro de Educación Médica e Investigaciones Clínicas (CEMIC), 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), Pontifical Catholic University of Paraná (PUCPR), Pontifical Catholic University of Paraná, Rashid Hospital, Imelda General Hospital, University of Otago [Dunedin, Nouvelle-Zélande], University of Birmingham [Birmingham], Kitasato University, NIHR Biomedical Research Centre [London], Guy's and St Thomas' NHS Foundation Trust-King‘s College London, Centre Hospitalier Universitaire de Liège (CHU-Liège), Hospital de São João [Porto], The Chinese University of Hong Kong [Hong Kong], Fondazione 'Policlinico Universitario A. Gemelli' [Rome], Cambridge University Hospitals - NHS (CUH), University of Cambridge [UK] (CAM), The University of Chicago Medicine [Chicago], Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)
Subjects: Evidence-Based Guidelines, medicine.medical_specialty, [SDV]Life Sciences [q-bio], International Cooperation, Settore MED/12 - GASTROENTEROLOGIA, education, Anti-Inflammatory Agents, MEDLINE, 030204 cardiovascular system & hematology, Risk Assessment, Inflammatory bowel disease, 03 medical and health sciences, 0302 clinical medicine, Fibrinolytic Agents, Risk Factors, Epidemiology, Humans, Medicine, In patient, Risk factor, Intensive care medicine, Hepatology, business.industry, Patient Acuity, Gastroenterology, Thrombosis, Guideline, Evidence-based medicine, Inflammatory Bowel Diseases, medicine.disease, digestive system diseases, 3. Good health, Hospitalization, Cardiovascular diseases, 030211 gastroenterology & hepatology, business
Abstract: Patients with inflammatory bowel disease (IBD) are at increased risk of thrombotic events. Therapies for IBD have the potential to modulate this risk. The aims of this Evidence-Based Guideline were to summarize available evidence and to provide practical recommendations regarding epidemiological aspects, prevention and drug-related risks of venous and arterial thrombotic events in patients with IBD. A virtual meeting took place in May 2020 involving 14 international IBD experts and 3 thrombosis experts from 12 countries. Proposed statements were voted upon in an anonymous manner. Agreement was defined as at least 75% of participants voting as ‘fully agree’ or ‘mostly agree’ with each statement. For each statement, the level of evidence was graded according to the Scottish Intercollegiate Guidelines Network (SIGN) grading system. Consensus was reached for 19 statements. Patients with IBD harbour an increased risk of venous and arterial thrombotic events. Thromboprophylaxis is indicated during hospitalization of any cause in patients with IBD. Disease activity is a modifiable risk factor in patients with IBD, and physicians should aim to achieve deep remission to reduce the risk. Exposure to steroids should be limited. Antitumour necrosis factor agents might be associated with a reduced risk of thrombotic events., Patients with inflammatory bowel disease (IBD) are at increased risk of thrombotic events. This Evidence-Based Guideline presents an international consensus on the prevention of venous and arterial thrombotic events in patients with IBD, and includes 19 recommendations for clinical practice.
Published: 2021
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17. Cluster Randomized Trials: Lessons for Inflammatory Bowel Disease Trials

Author: Ferdinando D'Amico, Bénédicte Caron, Laurent Peyrin-Biroulet, Silvio Danese, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), and Humanitas University [Milan] (Hunimed)
Subjects: Restricted randomization, medicine.medical_specialty, Randomization, [SDV]Life Sciences [q-bio], Population, Disease cluster, 01 natural sciences, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, medicine, Cluster Analysis, Humans, 030212 general & internal medicine, Cluster randomised controlled trial, 0101 mathematics, Intensive care medicine, education, Randomized Controlled Trials as Topic, Face validity, education.field_of_study, business.industry, 010102 general mathematics, Gastroenterology, General Medicine, Inflammatory Bowel Diseases, 3. Good health, Clinical trial, Research Design, business
Abstract: Randomized clinical trials are the gold standard for the development of new drugs. Clinical trials have become increasingly complex, in particular in the field of inflammatory bowel diseases. For this reason, a new study design called ‘cluster randomized trial’ has been introduced. Cluster randomized trials randomly assign groups of individuals within a population of interest, such as people in a particular research site, clinic or hospital, and measure the effects of an intervention at the individual level. In contrast to individual randomization, cluster randomization permits the evaluation of a cluster-level intervention, may be logistically simpler and less expensive than a conventional randomized trial, and can help reduce the effect of treatment contamination. An important aspect requiring particular attention in cluster randomized trials is the risk for imbalance of covariates at baseline which decreases the statistical power and precision of the results, and reduces face validity and credibility of the trial results. A variety of restricted randomization methods have been proposed to minimize risk of imbalance. Our aim here is to clarify the advantages and drawbacks of cluster randomized trials in order to properly interpret study results and to identify their role in upcoming inflammatory bowel disease trials.
Published: 2021
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18. Oesophageal Motility And Bolus Transit Abnormalities Increase In Parallel With The Severity Of Gastro-Oesophageal Reflux Disease

Author: Savarino, Edoardo, Gemignani, Lorenzo, Pohl, Daniel, Zentilin, Patrizia, Dulbecco, Pietro, Assandri, Lorenzo, Marabotto, Elisa, Bonfanti, Daria, Inferrera, Simona, Fazio, Valentina, Malesci, Alberto C, Tutuian, Radu, Savarino, Vincenzo, Gastroenterology Unit, Universita degli Studi di Padova, Division of Gastroenterology and Hepatology, Medical University of South Carolina [Charleston] (MUSC), University of Genoa (UNIGE), Division of Gastroenterology, Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed)-Humanitas University [Milan] (Hunimed), Gastroenterology, and Inselspital
Subjects: Adult, Male, Esophageal pH Monitoring, FUNCTIONAL HEARTBURN, NERD, Manometry, Severity of Illness Index, Barrett's esophagus, Young Adult, Electric Impedance, Humans, Prospective Studies, Gastrointestinal Transit, Aged, Retrospective Studies, digestive, oral, and skin physiology, Gastric Acidity Determination, Middle Aged, digestive system diseases, Italy, Case-Control Studies, Gastroesophageal Reflux, Regression Analysis, Medicine, Female, Peristalsis, Gastrointestinal Motility
Abstract: International audience; Introduction: Limited data are available regarding the frequency of oesophageal motility and bolus transit abnormalities in subgroups of patients with gastro-oesophageal reflux disease (GORD). Aim: To assess oesophageal motility and bolus transit in endoscopically-defined GORD subgroups. Methods: Patients (N=755) with typical reflux symptoms underwent upper endoscopy, conventional or impedance oesophageal manometry and/or impedance-pH testing. They were divided into: erosive oesophagitis (EO; N=340), Barrett Oesophagus (BO; N=106), non-erosive reflux disease (NERD; endoscopy−, abnormal pH and/or SAP/SI+; N=239) and functional heartburn (FH; endoscopy-, normal pH and SAP/SI-; N=70). Manometric patterns and bolus transit were defined according to previously published criteria. Results: Increasing GORD severity was associated with decreased lower oesophageal sphincter resting pressure (p
Published: 2011
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19. Defining the critical hurdles in cancer immunotherapy

Author: Andrea Nicolini, Francesco M. Marincola, William E. Carson, Paolo A. Ascierto, Michele Maio, Jedd D. Wolchok, Michael T. Lotze, Jirina Bartunkova, Weihua Xiao, Hauke Winter, Barbara Seliger, Jon M. Wigginton, Cedrik M. Britten, Ignacio Melero, Guido Kroemer, Neil L. Berinstein, Jill O'Donnell-Tormey, Heinz Zwierzina, Lothar Bergmann, Lloyd J. Old, Christian H. Ottensmeier, Jérôme Galon, Per thor Straten, Koji Kawakami, Michael Papamichail, Yutaka Kawakami, Michael I. Nishimura, Mary L. Disis, Steinar Aamdal, C. J. M. Melief, Pedro Romero, Kristen Hege, Wenru Song, Pawel Kalinski, Jonathan L. Bramson, Harpreet Singh-Jasuja, Jens Peter Marschner, Bernard A. Fox, Samir N. Khleif, Brad H. Nelson, Marij J. P. Welters, Elizabeth M. Jaffee, Patrick Hwu, Rik J. Scheper, Robert C. Rees, Giuseppe Masucci, Hideaki Tahara, Cristina Bonorino, Glenn Dranoff, Ernest C. Borden, William J. Murphy, Zhigang Tian, Michael B. Atkins, Robert O. Dillman, Thomas F. Gajewski, Hiroshi Shiku, Leif Håkansson, Michael J. Mastrangelo, Lisa H. Butterfield, Shukui Qin, Laurence Zitvogel, Harry Dolstra, Michele Guida, George Coukos, Mohamed L. Salem, Xuetao Cao, Giorgio Parmiani, Enrico Proietti, Ena Wang, Sylvia Janetzki, A. Raja Choudhury, Gerd Ritter, Hyam I. Levitsky, Kunle Odunsi, Kohzoh Imai, Paul von Hoegen, Christoph Huber, Réjean Lapointe, Antoni Ribas, Dolores J. Schendel, Pamela S. Ohashi, Beatrix Kotlan, Cécile Gouttefangeas, James H. Finke, Alfred E. Chang, Howard L. Kaufman, Lindy G. Durrant, Sjoerd H. van der Burg, Jared Gollob, Dainius Characiejus, Tara Withington, Padmanee Sharma, Ronald B. Herberman, Cristina Maccalli, Ulrich Keilholtz, Axel Hoos, Graham Pawelec, Fabio Grizzi, Tanja D. de Gruijl, F. Stephen Hodi, Ruggero Ridolfi, James P. Allison, Licia Rivoltini, Carl H. June, Rolf Kiessling, Department of Molecular Microbiology and Immunology, Oregon Health and Science University [Portland] (OHSU)-Knight Cancer Institute, Earle A. Chiles Research Institute, Providence Portland Medical Center-Robert W. Franz Research Center-Providence Cancer Center, Clinical Cooperation Group 'Immune Monitoring', German Research Center for Environmental Health-Helmholtz Centre Munich-Institute of Molecular Immunology, Division of Hematology Oncology, University of Pittsburgh Cancer Institute-Departments of Medicine, Department of Surgery, Cancer Institute-University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Department of Immunology, University of Pittsburgh Cancer Institute, Department of Clinical Cancer Research, The Norwegian Radium Hospital-Oslo University Hospital [Oslo], Memorial Sloane Kettering Cancer Center [New York], Howard Hughes Medical Institute (HHMI), Medical Oncology and Innovative Therapy, Instituto Nazionale Tumori-Fondazione 'G. Pascale', Beth Israel Deaconess Medical Center, Harvard Medical School [Boston] (HMS), Institute of Immunology, Charles University [Prague] (CU)-FOCIS Center of Excellence-2nd Medical School, Goethe-Universität Frankfurt am Main, IRX Therapeutics, Stanford University-ImmunoVaccine Inc., Instituto Nacional para o Controle do Câncer, Instituto de Pesquisas Biomédicas-PUCRS Faculdade de Biociências, Department of Solid Tumor Oncology, Cleveland Clinic, Department of Translational Hematology and Oncology Research, Department of Pathology, McMaster University [Hamilton, Ontario], University Medical Center Mainz, III. Medical Department, Ribological GmbH, Department of Medicine-University Medical Center of the Johannes Gutenberg-University-Clinical Development, BioNTech AG, Chinese Academy of Medical Sciences, Second Military Medical University-National Key Laboratory of Medical Immunology, Ohio State University [Columbus] (OSU), University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Institute of Oncology, Vilnius University [Vilnius]-Faculty of Medicine, Department of Medicine, University of Queensland [Brisbane], Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], Department of Medical Oncology, VU Medical Center-Cancer Center Amsterdam, Hoag Institute for Research and Education, Hoag Cancer Institute, Department of Laboratory Medicine, Radboud university [Nijmegen]-Nijmegen Centre for Molecular Life Sciences-Nijmegen Medical Centre [Nijmegen], Brigham and Women's Hospital [Boston], Dana-Farber Cancer Institute [Boston], Academic Department of Clinical Oncology, University of Nottingham, UK (UON), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Paris Descartes - Paris 5 (UPD5)-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), Alnylam Pharmaceuticals, Inc., Institute for Cell Biology, Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), Oncology Department, University of Lund, CanImGuide Therapeutics AB, University of California [San Francisco] (UCSF), University of California, Intrexon Corporation, Germantown, Bristol-Myers Squibb Company, Translational Oncology & Immunology, Centre TRON at the Mainz University Medical Center, Department of Melanoma Medical Oncology, The University of Texas M.D. Anderson Cancer Center [Houston], The Institute of Medical Science, The University of Tokyo (UTokyo), Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine [Baltimore]-Johns Hopkins University School of Medicine [Baltimore], ZellNet Consulting, Pathology and Laboratory Medicine, University of Pennsylvania [Philadelphia], Rush University Cancer Center, Rush University Medical Center [Chicago], School of Medicine and Public Health, Kyoto University [Kyoto], Division of Cellular Signaling, Institute for Advanced Medical Research, Dept. of Hematology and Medical Oncology, Charité Comprehensive Cancer Center, Cancer Vaccine Section, NCI, Department of Oncology - Pathology, Cancer Center Karolinska [Karolinska Institutet] (CCK), Karolinska Institutet [Stockholm]-Karolinska Institutet [Stockholm], Department of Molecular Immunology and Toxicology, Center of Surgical and Molecular Tumor pathology, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), School of Medicine, Johns Hopkins University (JHU)-Oncology Center, Department of Molecular Oncology, Foundation San Raffaele Scientific Institute, Medical Oncology and Immunotherapy, Istituto Toscano Tumori-University Hospital of Siena-Department of Oncology, Merck KGaA, Merck & Co. Inc, Thomas Jefferson University, Department of Oncology-Pathology, karolinska institute, CIMA, CUN and Medical School University of Navarra, Department of Immunohematology and Blood Transfusion, Leiden University Medical Center (LUMC), Davis Medical Center, Sacramento-University of California, Deeley Research Centre, BC Cancer Agency (BCCRC), Department of Internal Medicine, University of Pisa - Università di Pisa, Oncology Institute, Loyola University Medical Center (LUMC)-Cardinal Bernardin Cancer Center, Tumor Immunology and Immunotherapy Program, Roswell Park Cancer Institute [Buffalo]-Department of Gynecologic Oncology, Ontario Cancer Institute, University Health Network, Cancer Immunotherapy Consortium (CIC), Cancer Research Institute, Cancer Research, Ludwig Institute, Experimental Cancer Medicine Centre, University of Southampton-Faculty of Medicine, Cancer Immunology and Immunotherapy Center, Saint Savas Cancer Hospital, Unit of Immuno-Biotherapy of Melanoma and Solid Tumors, San Raffaele Scientific Institute, Center for Medical Research, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanita', Chinese PLA Cancer Center, Department of Oncology-The Eighty-First Hospital, The John van Geest Cancer Research Centre, School of Science and Technology-Nottingham Trent University, Jonsson Comprehensive Cancer Center, Immunoterapia e Terapia Cellulare Somatica, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.), Unit of Immunotherapy of Human Tumors, Istituto Nazionale Tumori-IRCCS Foundation, Division of Clinical Onco-Immunology, Université de Lausanne (UNIL)-Ludwig Center for Cancer Research, Immunology and Biotechnology Unit, Faculty of Science-Department of Zoology-Tanta University, VU University Medical Center [Amsterdam], Institute of Medical Immunology, Martin-Luther-Universität Halle Wittenberg (MLU), Departments of Immunology, Department of Cancer Vaccine, Mie University, Department of Immuno-gene Therapy, Immatics Biotechnologies GmbH, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen-Department of Immunology-Institute for Cell Biology, Millennium: The Takeda Oncology Company, Pfizer Oncology, Center for Cancer Immune Therapy (CCIT), Herlev and Gentofte Hospital-Department of Hematology, Department of Surgery and Bioengineering, The University of Tokyo (UTokyo)-Institute of Medical Science-Advanced Clinical Research Center, School of Life Sciences-University of Science & Technology of China [Suzhou], Institute of Immunopharmacology & Immunotherapy, Shandong University-School of Pharmaceutical Sciences, Experimental Cancer Immunology and Therapy, Leiden University Medical Center (LUMC)-Department of Clinical Oncology, Euraccine Consulting Group, Infectious Disease and Immunogenetics Section (IDIS), Department of Transfusion Medicine-Clinical Center-National Institute of Health NIH), Center for Human Immunology (CHI), National Institute of Health (NIH), Leiden University Medical Center (LUMC)-Department of Clinical Oncology (K1-P), Ludwig Maximilians University-Klinikum Grosshadern, Biological Therapy of Cancer, Medical and Surgical Services Organizations-International Society For Biological Therapy Of Cancer, School of Life Science-University of Science and Technology of China [Hefei] (USTC), Immunologie des tumeurs et immunothérapie (UMR 1015), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Department Haematology and Oncology, Innsbruck Medical University [Austria] (IMU), Medical Center, University of Chicago, Discovery Medicine-Oncology, Tumor Vaccine Group, University of Washington [Seattle]-Center for Translational Medicine in Women's Health, The work of CIMT-CIP was supported by a grant from the Wallace Coulter foundation (Florida, USA)., Helmholtz Centre Munich-Institute of Molecular Immunology-Helmholtz Zentrum München = German Research Center for Environmental Health, University of Pennsylvania-University of Pennsylvania, Radboud University [Nijmegen]-Nijmegen Centre for Molecular Life Sciences-Nijmegen Medical Centre [Nijmegen], Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Lund University [Lund], University of California [San Francisco] (UC San Francisco), University of California (UC), University of Pennsylvania, Kyoto University, Sacramento-University of California (UC), Université de Lausanne = University of Lausanne (UNIL)-Ludwig Center for Cancer Research, Klinikum Grosshadern-Ludwig-Maximilians University [Munich] (LMU), University of Science and Technology of China [Hefei] (USTC)-School of Life Science, Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), BMC, Ed., Computer Systems, Medical oncology laboratory, Pathology, CCA - Immuno-pathogenesis, CCA - Innovative therapy, Oregon Health and Science University-Knight Cancer Institute, Cancer Institute-University of Pittsburgh, The Norwegian Radium Hospital-Oslo University Hospital, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Institute, Howard Hughes Medical Institute, Ludwig Center for Cancer Immunotherapy, A Teaching Hospital of Harvard Medical School, Charles University [Prague]-FOCIS Center of Excellence-2nd Medical School, Stanford University [Stanford]-ImmunoVaccine Inc., Ohio State University [Columbus] ( OSU ), University of Michigan Medical Center, University of Pennsylvania Medical Center, Radboud university [Nijmegen]-Nijmegen Centre for Molecular Life Sciences-Nijmegen Medical Centre, University of Nottingham, UK ( UON ), Cleveland Clinic Foundation, Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -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 Clinico Humanitas [Milan] ( IRCCS Milan ), Humanitas University [Milan] ( Hunimed ), University of California [San Francisco] ( UCSF ), Harvard Medical School [Boston] ( HMS ), MD Anderson Cancer Center, The University of Tokyo, Rush University Medical Center, Cancer Center Karolinska [Karolinska Institutet] ( CCK ), Centre Hospitalier de l'Université de Montréal-Hôpital Notre-Dame Research Center ( CRCHUM ), Department of Medicine-University of Montreal, Johns Hopkins University ( JHU ) -Oncology Center, BC Cancer Agency ( BCCRC ), University of Pisa [Pisa], Loyola University Medical Center ( LUMC ) -Cardinal Bernardin Cancer Center, Cancer Immunotherapy Consortium ( CIC ), University of Southampton [Southampton]-Faculty of Medicine, Eberhard Karls Universität Tübingen, University of Lausanne-Ludwig Center for Cancer Research, Martin-Luther-University Halle-Wittenberg, Mie University Graduate School of Medicine, Eberhard Karls Universität Tübingen-Department of Immunology-Institute for Cell Biology, Center for Cancer Immune Therapy ( CCIT ), Herlev Hospital-Department of Hematology, The University of Tokyo-Institute of Medical Science-Advanced Clinical Research Center, Infectious Disease and Immunogenetics Section ( IDIS ), Center for Human Immunology ( CHI ), University of Science and Technology of China [Hefei] ( USTC ) -School of Life Science, Immunologie des tumeurs et immunothérapie ( UMR 1015 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Innsbruck Medical University [Austria] ( IMU ), Department of Medicine-Clinical Development, BioNTech AG-Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Universiteit Leiden-Universiteit Leiden, Roswell Park Cancer Institute [Buffalo] (RPCI)-Department of Gynecologic Oncology, Istituto Superiore di Sanità (ISS), Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Universiteit Leiden-Universiteit Leiden-Department of Clinical Oncology, and Universiteit Leiden-Universiteit Leiden-Department of Clinical Oncology (K1-P)
Subjects: medicine.medical_specialty, International Cooperation, medicine.medical_treatment, Alternative medicine, lcsh:Medicine, Translational research, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cancer Immunotherapy, General Biochemistry, Genetics and Molecular Biology, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Translational Research, Biomedical, 03 medical and health sciences, SDG 17 - Partnerships for the Goals, 0302 clinical medicine, Cancer immunotherapy, [SDV.CAN] Life Sciences [q-bio]/Cancer, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Neoplasms, medicine, Humans, In patient, 030304 developmental biology, Medicine(all), 0303 health sciences, geography, Summit, geography.geographical_feature_category, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Biochemistry, Genetics and Molecular Biology(all), business.industry, lcsh:R, Cancer, General Medicine, Public relations, medicine.disease, 3. Good health, Clinical trial, Immunotherapy, Neoplasms/therapy, Translational Medical Research, 030220 oncology & carcinogenesis, Immunology, Commentary, Working group, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators; others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet if overcome, have the potential to improve outcomes of patients with cancer. © 2011 Fox et al; licensee BioMed Central Ltd.
Published: 2011
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20. 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
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21. Motivation to pursue anti-TNFα treatment in patients with Crohn's disease – the SPACE motivation study

Author: Ferdinando D'Amico, Laurent Peyrin-Biroulet, Hervé Hagège, Luc Vandromme, Maria Nachury, Salim Benkhalifa, Xavier Hébuterne, Patrick Faure, Yoram Bouhnik, Stéphane Nahon, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Humanitas University [Milan] (Hunimed), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Polyclinique Courlancy (PC), Polyclinique de Courlancy, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7), Clinique Pasteur, Clinique Pasteur [Toulouse], Groupe Hospitalier Intercommunal Le Raincy-Montfermeil, Centre Hospitalier Intercommunal de Créteil (CHIC), Centre Hospitalier Universitaire de Nice (CHU Nice), Université Côte d'Azur (UCA), AbbVie, CHU Lille, Service de Gastro-entérologie et Nutrition[Rangueil], CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Institut des Maladies de l'Appareil Digestif, and Université de Nantes (UN)
Subjects: Adult, Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Disease, Satisfaction of patients with Crohn's disease questionnaire (SPACE-Q), Treatment satisfaction, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Surveys and Questionnaires, Internal medicine, medicine, Adalimumab, Humans, Treatment adherence, In patient, Longitudinal Studies, Prospective Studies, Prospective cohort study, Motivation, Crohn's disease, Hepatology, business.industry, Anti-tumor necrosis factor α, Gastroenterology, Middle Aged, medicine.disease, Infliximab, Chronic disorders, 3. Good health, Treatment Outcome, Patient Satisfaction, 030220 oncology & carcinogenesis, Linear Models, Female, Tumor Necrosis Factor Inhibitors, 030211 gastroenterology & hepatology, France, business, medicine.drug
Abstract: International audience; Background: Crohn's disease (CD) is a chronic disorder requiring long-term treatment. However, up to 20% of patients interrupt temporarily or permanently anti-TNFα. Primary aim was to identify internal and external factors influencing patient's motivation to pursue anti-TNFα in active CD.Methods: This was a French, multicentre, prospective study enrolling CD patients on anti-TNFα therapy since more than 3 months. Patients completed the Satisfaction of Patients with Crohn's Disease questionnaire (SPACE-Q) and other patient-reported-outcome tools at inclusion visit, and after 6 and 12 months.Results: A total of 274 patients were included: 146 (53.3%) received adalimumab, while 128 (46.7%) infliximab. Most patients (78%) were still treated with anti-TNFα 12 months after enrolment. Patients' perception of necessity (p = 0.01) and concerns (p
Published: 2020
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22. Fungal exposome, human health and unmet needs: a 2022 update with special focus on allergy

Author: Vitte, Joana, Michel, Moïse, Malinovschi, Andrei, Caminati, Marco, Odebode, Adeyinka, Annesi‐maesano, Isabella, Caimmi, Davide, Cassagne, Carole, Demoly, Pascal, Heffler, Enrico, Menu, Estelle, Nwaru, Bright, Sereme, Youssouf, Ranque, Stéphane, Raulf, Monika, Feleszko, Wojciech, Janson, Christer, Galán, Carmen, Allergic Bronchopulmonary Aspergillosis, Eaaci Task Force On, Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), 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), Assistance Publique - Hôpitaux de Marseille (APHM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Uppsala University, Università degli studi di Verona = University of Verona (UNIVR), Kampala International University, Département pneumologie et addictologie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Médecine de précision par intégration de données et inférence causale (PREMEDICAL), 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)-Institut Desbrest de santé publique (IDESP), 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 de Montpellier (UM), Humanitas Clinical and Research Center [Rozzano, Milan, Italy], Humanitas University [Milan] (Hunimed), Sahlgrenska Academy at University of Gothenburg [Göteborg], University of Gothenburg (GU), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Ruhr-Universität Bochum [Bochum], Medical University of Warsaw - Poland, and Universidad de Córdoba = University of Córdoba [Córdoba]
Subjects: MESH: Exposome, MESH: Humans, MESH: Hypersensitivity, Respiratory Medicine and Allergy, Immunology, fungus, exposome, yeast, allergy, MESH: Biomarkers, allergic bronchopulmonary aspergillosis, microbiota, Immunology and Allergy, Humans, mycobiota, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, hypersensitivity, allergic broncho-pulmonary aspergillosis, immunoglobulin, Biomarkers, Lungmedicin och allergi
Abstract: International audience; Humans inhale, ingest, and touch thousands of fungi each day. The ubiquity and diversity of the fungal kingdom, reflected by its complex taxonomy, are in sharp contrast with our scarce knowledge about its distribution, pathogenic effects, and effective interventions at the environmental and individual levels. Here, we present an overview of salient features of fungi as permanent players of the human exposome and key determinants of human health, through the lens of fungal allergy and other fungal hypersensitivity reactions. Improved understanding of the fungal exposome sheds new light on the epidemiology of fungal-related hypersensitivity diseases, their immunological substratum, the currently available methods, and biomarkers for environmental and medical fungi. Unmet needs are described and potential approaches are highlighted as perspectives.
Published: 2022
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23. Association between tracheostomy timing and outcomes for older critically ill COVID-19 patients:prospective observational study in European intensive care units

Author: Raphael Romano Bruno, Bertrand Guidet, Michael Beil, Peter Vernon van Heerden, Kamil Polok, Bernardo Bollen Pinto, Bernhard Wernly, Finn H. Andersen, Antonio Artigas, Michael Joannidis, Wojciech Szczeklik, Brian Marsh, Rui Moreno, Dorota Studzińska, Maurizio Cecconi, Joerg C. Schefold, Hans Flaatten, Sigal Sviri, Sandra Oeyen, Dylan W. de Lange, Jakub Fronczek, Jesper Fjølner, Christian Jung, Susannah Leaver, Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), The Hebrew University of Jerusalem (HUJ), University of Bergen (UiB), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Réanimation Médicale [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), University Medical Center [Utrecht], Aarhus University Hospital, St George’s University Hospitals, Hadassah Hebrew University Medical Center [Jerusalem], Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), CIBER de Epidemiología y Salud Pública (CIBERESP), Hôpitaux Universitaires de Genève (HUG), Bern University Hospital [Berne] (Inselspital), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Ghent University Hospital, Mater Misericordiae University Hospital (The Mater Hospital), Norwegian University of Science and Technology (NTNU), NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Humanitas University [Milan] (Hunimed), and Gestionnaire, Hal Sorbonne Université
Subjects: Male, medicine.medical_specialty, Time Factors, Critical Care, Coronavirus disease 2019 (COVID-19), intensive care units, Critical Illness, medicine.medical_treatment, [SDV]Life Sciences [q-bio], tracheostomy, mechanical ventilation, law.invention, law, Intensive care, medicine, Humans, Intubation, Prospective Studies, Clinical Investigation, Correlation of Data, 610 Medicine & health, Prospective cohort study, outcome assessment, Aged, Mechanical ventilation, business.industry, Critically ill, COVID-19, healthcare, Length of Stay, Respiration, Artificial, Intensive care unit, Europe, Survival Rate, Health Care, [SDV] Life Sciences [q-bio], Treatment Outcome, Anesthesiology and Pain Medicine, Emergency medicine, Female, Observational study, business
Abstract: BACKGROUND Tracheostomy is performed in patients expected to require prolonged mechanical ventilation, but to date optimal timing of tracheostomy has not been established. The evidence concerning tracheostomy in COVID-19 patients is particularly scarce. We aimed to describe the relationship between early tracheostomy (��10 days since intubation) and outcomes for patients with COVID-19. METHODS This was a prospective cohort study performed in 152 centres across 16 European countries from February to December 2020. We included patients aged ��70 yr with confirmed COVID-19 infection admitted to an intensive care unit, requiring invasive mechanical ventilation. Multivariable analyses were performed to evaluate the association between early tracheostomy and clinical outcomes including 3-month mortality, intensive care length of stay, and duration of mechanical ventilation. RESULTS The final analysis included 1740 patients with a mean age of 74 yr. Tracheostomy was performed in 461 (26.5%) patients. The tracheostomy rate varied across countries, from 8.3% to 52.9%. Early tracheostomy was performed in 135 (29.3%) patients. There was no difference in 3-month mortality between early and late tracheostomy in either our primary analysis (hazard ratio [HR]=0.96; 95% confidence interval [CI], 0.70-1.33) or a secondary landmark analysis (HR=0.78; 95% CI, 0.57-1.06). CONCLUSIONS There is a wide variation across Europe in the timing of tracheostomy for critically ill patients with COVID-19. However, we found no evidence that early tracheostomy is associated with any effect on survival amongst older critically ill patients with COVID-19. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov NCT04321265.
Published: 2022
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24. State-of-the-art CT and MR imaging and assessment of atherosclerotic carotid artery disease: the reporting-a consensus document by the European Society of Cardiovascular Radiology (ESCR)

Author: Luca Saba, Christian Loewe, Thomas Weikert, Michelle C. Williams, Nicola Galea, Ricardo P. J. Budde, Rozemarijn Vliegenthart, Birgitta K. Velthuis, Marco Francone, Jens Bremerich, Luigi Natale, Konstantin Nikolaou, Jean-Nicolas Dacher, Charles Peebles, Federico Caobelli, Alban Redheuil, Marc Dewey, Karl-Friedrich Kreitner, Rodrigo Salgado, Cardiovascular Centre (CVC), Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), Digital Healthcare (DH), Radiology & Nuclear Medicine, University of Cagliari, Medizinische Universität Wien = Medical University of Vienna, University of Basel (Unibas), University of Edinburgh, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Groningen [Groningen], University Medical Center [Utrecht], Humanitas University [Milan] (Hunimed), Istituto Clinico Humanitas [Milan] (IRCCS Milan), Catholic University of the Sacred Heart [Rome, Italy] (CUSH), Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, CHU Rouen, 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), University Hospital Southampton NHS Foundation Trust, University of Bern, Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], University Medical Center [Mainz], Antwerp University Hospital [Edegem] (UZA), and DACHER, Jean Nicolas
Subjects: Computer. Automation, Atherosclerotic plaque, Consensus, carotid artery diseases, 610 Medicine & health, General Medicine, MR, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, CT angiography, consensus, Carotid artery diseases, Radiology, Nuclear Medicine and imaging, Human medicine
Abstract: Abstract The European Society of Cardiovascular Radiology (ESCR) is the European specialist society of cardiac and vascular imaging. This society’s highest priority is the continuous improvement, development, and standardization of education, training, and best medical practice, based on experience and evidence. The present intra-society consensus is based on the existing scientific evidence and on the individual experience of the members of the ESCR writing group on carotid diseases, the members of the ESCR guidelines committee, and the members of the executive committee of the ESCR. The recommendations published herein reflect the evidence-based society opinion of ESCR. The purpose of this second document is to discuss suggestions for standardized reporting based on the accompanying consensus document part I. Key Points • CT and MR imaging-based evaluation of carotid artery disease provides essential information for risk stratification and prediction of stroke. • The information in the report must cover vessel morphology, description of stenosis, and plaque imaging features. • A structured approach to reporting ensures that all essential information is delivered in a standardized and consistent way to the referring clinician.
Published: 2022
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25. Interpretation of 2-[F-18]FDG PET/CT in Hodgkin lymphoma patients treated with immune checkpoint inhibitors

Author: Guillaume Manson, Amaeshi Chukwunonye Lemchukwu, Fatima-Zohra Mokrane, Egesta Lopci, Nicolas Aide, Laetitia Vercellino, Roch Houot, Laurent Dercle, Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer (MOBIDIC), Université de Rennes (UR)-Etablissement français du sang [Rennes] (EFS Bretagne)-Institut National de la Santé et de la Recherche Médicale (INSERM), Albert Einstein College of Medicine [New York], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Columbia University Medical Center (CUMC), Columbia University [New York], The authors state that this work has not received any funding., and Chard-Hutchinson, Xavier
Subjects: [SDV] Life Sciences [q-bio], Immune checkpoint inhibitors, PET, [SDV.CAN] Life Sciences [q-bio]/Cancer, hemic and lymphatic diseases, [SDV]Life Sciences [q-bio], Radiology, Nuclear Medicine and imaging, [SDV.CAN]Life Sciences [q-bio]/Cancer, General Medicine, Immunotherapy, Pseudoprogression indeterminate response, Hodgkin lymphoma
Abstract: International audience; The development of immunotherapy has revolutionized cancer treatment, improving the outcome and survival of many patients. Immune checkpoint inhibitors (ICIs), the most common form of immunotherapy, use antibodies to restore T-cells' anti-tumor activity. Immune checkpoint inhibitors are gaining ground in the therapeutic strategy across various cancers. Although widely used in solid tumors, ICIs have shown remarkable efficacy in patients with Hodgkin lymphoma. 2-[F-18]Fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET)/CT is the gold standard to stage and monitor responses in Hodgkin lymphoma. This article reviewed the use of 2-[F-18]FDG-PET/CT in patients with Hodgkin lymphoma treated with ICI, focusing on image interpretation for response monitoring and detecting adverse events.
Published: 2022
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26. Diversion-p64 : results from an international, prospective, multicenter, single-arm post-market study to assess the safety and effectiveness of the p64 flow modulation device

Author: Joachim Klisch, Christian L. Roth, Frédéric Clarençon, Stefanita Dima, Xavier Barreau, Massimo Dall’Olio, Hans Henkes, Ana-Paula Narata, Peter Keston, Stanimir Sirakov, Luc Stockx, Alain Bonafe, Tony Goddard, Marcin Miś, Francis Turjman, Nunzio Paolo Nuzzi, Laurent Spelle, Marta Aguilar Pérez, Alexander Sirakov, Cezary Wałęsa, Ansgar Berlis, Sergey Yakovlev, Christian Loehr, Pedro Lylyk, Christina Wendl, Peter Schramm, A. V. Petrov, Carlos Bleise, Tine Willems, A. Clifton, Laurent Pierot, Gregory Gascou, Neuroradiologie [Hôpital Gui de Chauliac], Hôpital Gui de Chauliac [Montpellier], La Sagrada Familia Clinic/Clínica La Sagrada Familia [Buenos Aires, Argentina] (LSFC), St. Ivan Rilski University Hospital, Ziekenhuis Oost-Limburg (ZOL), Service de neuroradiologie [Lyon], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Almazov National Medical Research Centre (St. Petersburg), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Groupe hospitalier Pellegrin, Klinikum Vest GmbH, Klinikum Augsburg, Hôpital Maison Blanche, Centre Hospitalier Universitaire de Reims (CHU Reims), Wroclaw Medical University [Wrocław, Pologne], Leeds Teaching Hospitals NHS Trust, St George’s University Hospitals, Helios Klinikum [Erfurt], Service de Neuroradiologie [CHU de Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Faculté de Médecine Paris-Saclay, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)-Université Paris-Saclay, Service de Neuroradiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), NHS Lothian, Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), University Hospital Regensburg, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Adult, Male, medicine.medical_specialty, medicine.medical_treatment, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Aneurysm, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Occlusion, medicine, Medicine and Health Sciences, Humans, Prospective Studies, ddc:610, Prospective cohort study, Stroke, Aged, Retrospective Studies, medicine.diagnostic_test, business.industry, Incidence (epidemiology), Mortality rate, Endovascular Procedures, Stent, flow diverter, Intracranial Aneurysm, General Medicine, Middle Aged, medicine.disease, Embolization, Therapeutic, 3. Good health, Surgery, Cerebral Angiography, Treatment Outcome, Angiography, aneurysm, Female, Stents, stent, Neurology (clinical), business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: BackgroundThe use of flow diversion to treat intracranial aneurysms has increased in recent years.ObjectiveTo assess the safety and angiographic efficacy of the p64 flow modulation device.MethodsDiversion-p64 is an international, prospective, multicenter, single-arm, study conducted at 26 centers. The p64 flow modulation device was used to treat anterior circulation aneurysms between December 2015 and January 2019. The primary safety endpoint was the incidence of major stroke or neurologic death at 3–6 months, with the primary efficacy endpoint being complete aneurysm occlusion (Raymond-Roy Occlusion Classification 1) on follow-up angiography.ResultsA total of 420 patients met the eligibility criteria and underwent treatment with the p64 flow modulation device (mean age 55±12.0 years, 86.2% female). Mean aneurysm dome width was 6.99±5.28 mm and neck width 4.47±2.28 mm. Mean number of devices implanted per patient was 1.06±0.47, with adjunctive coiling performed in 14.0% of the cases. At the second angiographic follow-up (mean 375±73 days), available for 343 patients (81.7%), complete aneurysm occlusion was seen in 287 (83.7%) patients. Safety data were available for 413 patients (98.3%) at the first follow-up (mean 145±43 days) with a composite morbidity/mortality rate of 2.42% (n=10).ConclusionsDiversion-p64 is the largest prospective study using the p64 flow modulation device. The results of this study demonstrate that the device has a high efficacy and carries a low rate of mortality and permanent morbidity.
Published: 2022
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27. Biliary tract cancer:ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up ☆

Author: A. Vogel, J. Bridgewater, J. Edeline, R.K. Kelley, H.J. Klümpen, D. Malka, J.N. Primrose, L. Rimassa, A. Stenzinger, J.W. Valle, M. Ducreux, Internal medicine, Medical School of Hannover (MHH), University College of London [London] (UCL), CRLCC Eugène Marquis (CRLCC), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of California [San Francisco] (UC San Francisco), University of California (UC), University of Amsterdam [Amsterdam] (UvA), Amsterdam UMC - Amsterdam University Medical Center, Dynamique des cellules tumorales (UMR1279), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Mutualiste de Montsouris (IMM), University Hospital Southampton NHS Foundation Trust, Humanitas University [Milan] (Hunimed), Heidelberg University Hospital [Heidelberg], University of Manchester [Manchester], Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), and Jonchère, Laurent
Subjects: gallbladder cancer, [SDV] Life Sciences [q-bio], Oncology, treatment, [SDV.CAN] Life Sciences [q-bio]/Cancer, diagnosis, precision medicine, [SDV]Life Sciences [q-bio], follow-up, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematology, cholangiocarcinoma
Abstract: International audience; No abstract available
Published: 2022
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28. Managing hematological cancer patients during the COVID-19 pandemic: an ESMO-EHA interdisciplinary expert consensus

Author: Buske, C., Dreyling, M., Alvarez-Larran, A., Apperley, J., Arcaini, L., Besson, C., Bullinger, L., Corradini, P., Giovanni Della Porta, M., Dimopoulos, M., D'Sa, S., Eich, H. T., Foa, R., Ghia, P., da Silva, M. G., Gribben, J., Hajek, R., Harrison, C., Heuser, M., Kiesewetter, B., Kiladjian, J. J., Kroger, N., Moreau, P., Passweg, J. R., Peyvandi, F., Rea, D., Ribera, J. -M., Robak, T., San-Miguel, J. F., Santini, V., Sanz, G., Sonneveld, P., von Lilienfeld-Toal, M., Wendtner, C., Pentheroudakis, G., Passamonti, F., Hematology, Buske, C., Dreyling, M., Alvarez-Larran, A., Apperley, J., Arcaini, L., Besson, C., Bullinger, L., Corradini, P., Giovanni Della Porta, M., Dimopoulos, M., D'Sa, S., Eich, H. T., Foa, R., Ghia, P., da Silva, M. G., Gribben, J., Hajek, R., Harrison, C., Heuser, M., Kiesewetter, B., Kiladjian, J. J., Kroger, N., Moreau, P., Passweg, J. R., Peyvandi, F., Rea, D., Ribera, J. -M., Robak, T., San-Miguel, J. F., Santini, V., Sanz, G., Sonneveld, P., von Lilienfeld-Toal, M., Wendtner, C., Pentheroudakis, G., Passamonti, F., Universitätsklinikum Ulm - University Hospital of Ulm, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Imperial College London, Hammersmith Hospital NHS Imperial College Healthcare, Fondazione IRCCS Policlinico San Matteo [Pavia], Università degli Studi di Pavia = University of Pavia (UNIPV), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre Hospitalier de Versailles André Mignot (CHV), Charité Campus Virchow-Klinikum (CVK), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Freie Universität Berlin, Humboldt University Of Berlin, Medical Oncology Unit, Dept of Medical Oncology and Hematology [Fondazione IRCCS Istituto Nazionale Tumori, Milan], Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], Università degli Studi di Milano = University of Milan (UNIMI), Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), National and Kapodistrian University of Athens (NKUA), University College London Hospitals (UCLH), NHS Foundation Trust [London], The Royal Marsden, Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), IRCCS Ospedale San Raffaele [Milan, Italy], Queen Mary University of London (QMUL), Lékařská fakulta / Faculty of Medicine [University of Ostrava], Ostravská univerzita / University of Ostrava, Medizinische Universität Wien = Medical University of Vienna, Université Paris Cité (UPCité), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University Hospital Hamburg-Eppendorf, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Centre hospitalier universitaire de Nantes (CHU Nantes), University Hospital Basel [Basel], Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Department of Physiopatology and Transplantation, University of Milan (DEPT), Josep Carreras Leukaemia Research Institute (IJC), Universitat Autònoma de Barcelona (UAB), Medical University of Łódź (MUL), Clínica Universidad de Navarra [Pamplona], Azienda Ospedaliero-Universitaria Careggi [Firenze] (AOUC), Università degli Studi di Firenze = University of Florence (UniFI), Jena University Hospital [Jena], Ludwig Maximilian University [Munich] (LMU), Leibniz Institute for Natural Product Research and Infection Biology (Hans Knoell Institute), Universitá degli Studi dell’Insubria = University of Insubria [Varese] (Uninsubria), Boehringer Ingelheim, BI, Amgen, Bristol-Myers Squibb, BMS, Pfizer, Astellas Pharma US, APUS, AstraZeneca, Bayer, Novartis, Roche, Sanofi, Gilead Sciences, Celgene, AbbVie, Meso Scale Diagnostics, MSD, Takeda Pharmaceutical Company, TPC, Janssen Pharmaceuticals, Merck KGaA, Jazz Pharmaceuticals, Deutsche Forschungsgemeinschaft, DFG, Bundesministerium für Bildung und Forschung, BMBF, Daiichi-Sankyo, José Carreras Leukämie-Stiftung, Deutsche Krebshilfe, Ipsen, The panel would like to acknowledge the work of Klizia Marinoni and Delanie Young, from the Scientific and Medical Division at ESMO, for the project coordination and editorial assistance. None declared. CB reports honoraria from Roche/Genentech, Janssen, BeiGene, Novartis, Pfizer, Incyte, AbbVie, Gilead Sciences, Celltrion, MorphoSys, Regeneron, he reports consulting or advisory role: Gilead Sciences, Janssen, Roche, Pfizer, BeiGene, Celltrion, AbbVie, Incyte, Regeneron, MorphoSys, Novartis, he reports speaker's engagement: Roche, Janssen, BeiGene, Celltrion, AbbVie, Pfizer, Gilead Sciences, he reports research funding: Roche/Genentech, Janssen, Celltrion, Merck Sharp & Dohme (MSD), Pfizer, Amgen. MD reports honoraria as Advisory Board Member of AstraZeneca, Bayer, BeiGene, Celgene, Genmab, Gilead, Incyte, Janssen, Lilly, MorphoSys, Novartis, Roche, he reports honoraria for speaker's engagement from Amgen, AstraZeneca, Bayer, Celgene, Gilead, Janssen, Novartis, Roche, he reports institutional research grants from AbbVie, Bayer, Gilead, Celgene, Janssen, Roche. AA-L has declared no conflicts of interest. JA reports personal financial interests as advisory board and invited speaker from Incyte, advisory board from Mallinckrodt, advisory board and invited speaker from Novartis, advisory board and invited speaker from Pfizer, she reports non-financial interests as principal investigator from Incyte, principal investigator from Novartis. LA received advisory honoraria from Roche, Celgene, Janssen-Cilag, Verastem, Eusa Pharma, Incyte, ADC Therapeutics and Gilead, research support from Gilead, and travel expenses from Roche, Celgene, Janssen-Cilag, and Eusa Pharma, speakers bureau from Novartis. CB has declared no conflicts of interest. LB reports Advisory Committee activities for AbbVie, Amgen, Astellas, Bristol Myers Squibb (BMS), Celgene, Daiichi Sankyo, Gilead, Hexal, Janssen, Jazz Pharmaceuticals, Menarini, Novartis, Pfizer, Sanofi, Seattle Genetics and has research support from Bayer and Jazz Pharmaceuticals. PC has declared no conflicts of interest. MGDP has declared no conflicts of interest. MD reports personal fees from Amgen, personal fees from Takeda, personal fees from Janssen, personal fees from BeiGene, personal fees from BMS, outside the submitted work. SD reports personal financial interests as advisory board, invited speaker, fellow funding, and coordinating PI from BeiGene, writing engagement from Karger, advisory board and coordinating PI from Sanofi, funding, and other from Janssen, she reports non-financial interests as advisory role at British Society for Haematology Lymphoma Special Interest Group, advisory role at Lymphoma Action, member of board of directors at WMUK Charity. HTE has declared no conflicts of interest. RF reports honoraria for advisory boards and/or speaker bureau from Janssen, Gilead, AbbVie, Amgen, Novartis, Roche, Incyte, Pfizer, all outside the submitted work. PG reports grants and personal fees from AbbVie, grants and personal fees from Acerta/AstraZeneca, personal fees from BeiGene, personal fees from Celgene/Juno/BMS, grants and personal fees from Janssen, personal fees from Lilly/Loxo, personal fees from MEI, personal fees from Roche, personal fees from Sanofi, personal fees from ArQule/MSD, outside the submitted work, MGdS reports grants, personal fees, non-financial support and other from Gilead Sciences, grants from AstraZeneca, personal fees, non-financial support, and other from Janssen Cilag, personal fees and non-financial support from Roche, non-financial support from AbbVie, personal fees and non-financial support from BMS, personal fees and non-financial support from MSD, personal fees and non-financial support from Takeda, personal fees from Novartis, personal fees from ADC Therapeutics, outside the submitted work. JG reports personal fees from AbbVie, grants and personal fees from AstraZeneca, grants and personal fees from BMS/Celgene, grants and personal fees from Janssen, personal fees from Kite/Gilead, personal fees from MorphoSys, personal fees from Novartis, personal fees from TG Therapeutics, outside the submitted work. RH has had a consultant or advisory relationship with Janssen, Amgen, Celgene, AbbVie, BMS, Novartis, PharmaMar, and Takeda, has received honoraria from Janssen, Amgen, Celgene, BMS, PharmaMar, and Takeda, has received research funding from Janssen, Amgen, Celgene, BMS, Novartis, and Takeda. CH reports grants and personal fees from Novartis, grants and personal fees from BMS, personal fees from Sierra Oncology, personal fees from CTI pharmaceuticals, personal fees from Jannsen, personal fees from Geron, grants and personal fees from AOP Orphan Pharma, personal fees from Galecto, grants, personal fees and other from Constellation, outside the submitted work. MH reports personal fees from Novartis, personal fees from Pfizer, personal fees from Roche, personal fees from AbbVie, personal fees from Daiichi Sankyo, personal fees from Bayer Pharma AG, personal fees from Jazz Pharmaceuticals, personal fees from BMS, personal fees from Tolremo, outside the submitted work. BK has received honoraria for lectures from Ipsen, Novartis and MSD (all outside of the submitted work). J-JK reports consulting fees and honoraria from Novartis, consulting fees from AbbVie, honoraria from AOP Orphan Pharma, participation on a monitoring board or advisory board from BMS/Celgene, participation on a monitoring board or advisory board from Incyte. NK reports grants and honoraria from Neovii, honoraria from Sanofi, grants and honoraria from Jazz, grants and honoraria from Celgene, grants and honoraria from Riemser, honoraria from Gilead/Kite, honorarium from AOP Oprhan Pharma, grants and honorarium from Novartis, honorarium from Amgen. PM reports personal fees from Celgene, Amgen, Janssen, AbbVie, Sanofi, outside the submitted work. JP has declared no conflicts of interest. FP has declared no conflicts of interest. DR received honoraria from Incyte, Novartis Pharma, Pfizer, clinical trial steering committee membership: Novartis, membership on advisory boards: Incyte, Novartis Pharma, Pfizer. J-MR reports grants and honoraria from Novartis, Amgen, Pfizer, Takeda, Incyte, and Servier. TR has declared no conflicts of interest. JF-M reports consulting and advisory boards honoraria (received by CUN ) from AbbVie, Amgen, BMS, Celgene, Janssen, GlaxoSmithKline, Karyopharm, MSD, Novartis, Takeda, Sanofi, SecuraBio, Regeneron, Roche, outside the submitted work. VS has declared no conflicts of interest. GFS reports personal fees and other from AbbVie, other from Amgen, other from Astellas, other from Boehringer-Ingelheim, grants, personal fees and other from Celgene, other from Helsinn Healthcare, grants, personal fees, and other from Janssen-Cilag, grants and other from Novartis, other from Onconova, grants, personal fees and other from Roche, and other from Takeda, outside the submitted work. PS reports honoraria from Amgen, Celgene, Janssen, Karyopharm, SkylineDx, Takeda, and research support from Celgene, Janssen, Amgen, Takeda, BMS, SkylineDx, Karyopharm, all outside the submitted work. MvL-T has received travel grants and honoraria from Celgene, Gilead, Chugai, Janssen, Novartis, Amgen, Takeda, BMS, Medac, Oncopeptides, Merck, CDDF, Pfizer, Medac, Thermo Fisher, AstraZeneca, is a consultant for Celgene, Gilead, Oncopeptides, MSD, 4D Pharma, Janssen, Shionogi and received research funding from BMBF, Deutsche Jose Carreras Leuk?mie-Stiftung, IZKF Jena, Novartis, Gilead, Deutsche Krebshilfe, Celgene, Oncopeptides, Deutsche Forschungsgemeinschaft (DFG). CW has declared no conflicts of interest. GP reports grants from Amgen, grants, personal fees and non-financial support from Merck, grants and non-financial support from AstraZeneca, grants and personal fees from Roche, grants and personal fees from BMS, grants from Lilly, grants and personal fees from MSD, grants and personal fees from Novartis, outside the submitted work. FP reports grants from Novartis, Celgene, BMS, Abbvie, Karyopharma, Janssen., MGdS reports grants, personal fees, non-financial support and other from Gilead Sciences, grants from AstraZeneca, personal fees, non-financial support, and other from Janssen Cilag, personal fees and non-financial support from Roche, non-financial support from AbbVie, personal fees and non-financial support from BMS, personal fees and non-financial support from MSD, personal fees and non-financial support from Takeda, personal fees from Novartis, personal fees from ADC Therapeutics, outside the submitted work., MvL-T has received travel grants and honoraria from Celgene, Gilead, Chugai, Janssen, Novartis, Amgen, Takeda, BMS, Medac, Oncopeptides, Merck, CDDF, Pfizer, Medac, Thermo Fisher, AstraZeneca, is a consultant for Celgene, Gilead, Oncopeptides, MSD, 4D Pharma, Janssen, Shionogi and received research funding from BMBF, Deutsche Jose Carreras Leukämie-Stiftung, IZKF Jena, Novartis, Gilead, Deutsche Krebshilfe, Celgene, Oncopeptides, Deutsche Forschungsgemeinschaft (DFG)., and HAL UVSQ, Équipe
Subjects: Cancer Research, Consensus, consensus manuscript, COVID-19, hematological malignancies, COVID-19, consensus manuscript, hematological malignancies, education, [SDV.CAN]Life Sciences [q-bio]/Cancer, COVID-19 Testing, Humans, Pandemics, Hematologic Neoplasms, [SDV.CAN] Life Sciences [q-bio]/Cancer, Oncology, SDG 3 - Good Health and Well-being, Original Research
Abstract: The panel would like to acknowledge the work of Klizia Marinoni and Delanie Young, from the Scientific and Medical Division at ESMO, for the project coordination and editorial assistance. None declared. CB reports honoraria from Roche/Genentech, Janssen, BeiGene, Novartis, Pfizer, Incyte, AbbVie, Gilead Sciences, Celltrion, MorphoSys, Regeneron; he reports consulting or advisory role: Gilead Sciences, Janssen, Roche, Pfizer, BeiGene, Celltrion, AbbVie, Incyte, Regeneron, MorphoSys, Novartis; he reports speaker's engagement: Roche, Janssen, BeiGene, Celltrion, AbbVie, Pfizer, Gilead Sciences; he reports research funding: Roche/Genentech, Janssen, Celltrion, Merck Sharp & Dohme (MSD), Pfizer, Amgen. MD reports honoraria as Advisory Board Member of AstraZeneca, Bayer, BeiGene, Celgene, Genmab, Gilead, Incyte, Janssen, Lilly, MorphoSys, Novartis, Roche; he reports honoraria for speaker's engagement from Amgen, AstraZeneca, Bayer, Celgene, Gilead, Janssen, Novartis, Roche; he reports institutional research grants from AbbVie, Bayer, Gilead, Celgene, Janssen, Roche. AA-L has declared no conflicts of interest. JA reports personal financial interests as advisory board and invited speaker from Incyte, advisory board from Mallinckrodt, advisory board and invited speaker from Novartis, advisory board and invited speaker from Pfizer; she reports non-financial interests as principal investigator from Incyte, principal investigator from Novartis. LA received advisory honoraria from Roche, Celgene, Janssen-Cilag, Verastem, Eusa Pharma, Incyte, ADC Therapeutics and Gilead; research support from Gilead, and travel expenses from Roche, Celgene, Janssen-Cilag, and Eusa Pharma; speakers bureau from Novartis. CB has declared no conflicts of interest. LB reports Advisory Committee activities for AbbVie, Amgen, Astellas, Bristol Myers Squibb (BMS), Celgene, Daiichi Sankyo, Gilead, Hexal, Janssen, Jazz Pharmaceuticals, Menarini, Novartis, Pfizer, Sanofi, Seattle Genetics and has research support from Bayer and Jazz Pharmaceuticals. PC has declared no conflicts of interest. MGDP has declared no conflicts of interest. MD reports personal fees from Amgen, personal fees from Takeda, personal fees from Janssen, personal fees from BeiGene, personal fees from BMS, outside the submitted work. SD reports personal financial interests as advisory board, invited speaker, fellow funding, and coordinating PI from BeiGene, writing engagement from Karger, advisory board and coordinating PI from Sanofi, funding, and other from Janssen; she reports non-financial interests as advisory role at British Society for Haematology Lymphoma Special Interest Group, advisory role at Lymphoma Action, member of board of directors at WMUK Charity. HTE has declared no conflicts of interest. RF reports honoraria for advisory boards and/or speaker bureau from Janssen, Gilead, AbbVie, Amgen, Novartis, Roche, Incyte, Pfizer, all outside the submitted work. PG reports grants and personal fees from AbbVie, grants and personal fees from Acerta/AstraZeneca, personal fees from BeiGene, personal fees from Celgene/Juno/BMS, grants and personal fees from Janssen, personal fees from Lilly/Loxo, personal fees from MEI, personal fees from Roche, personal fees from Sanofi, personal fees from ArQule/MSD, outside the submitted work;, MGdS reports grants, personal fees, non-financial support and other from Gilead Sciences, grants from AstraZeneca, personal fees, non-financial support, and other from Janssen Cilag, personal fees and non-financial support from Roche, non-financial support from AbbVie, personal fees and non-financial support from BMS, personal fees and non-financial support from MSD, personal fees and non-financial support from Takeda, personal fees from Novartis, personal fees from ADC Therapeutics, outside the submitted work. JG reports personal fees from AbbVie, grants and personal fees from AstraZeneca, grants and personal fees from BMS/Celgene, grants and personal fees from Janssen, personal fees from Kite/Gilead, personal fees from MorphoSys, personal fees from Novartis, personal fees from TG Therapeutics, outside the submitted work. RH has had a consultant or advisory relationship with Janssen, Amgen, Celgene, AbbVie, BMS, Novartis, PharmaMar, and Takeda; has received honoraria from Janssen, Amgen, Celgene, BMS, PharmaMar, and Takeda; has received research funding from Janssen, Amgen, Celgene, BMS, Novartis, and Takeda. CH reports grants and personal fees from Novartis, grants and personal fees from BMS, personal fees from Sierra Oncology, personal fees from CTI pharmaceuticals, personal fees from Jannsen, personal fees from Geron, grants and personal fees from AOP Orphan Pharma, personal fees from Galecto, grants, personal fees and other from Constellation, outside the submitted work. MH reports personal fees from Novartis, personal fees from Pfizer, personal fees from Roche, personal fees from AbbVie, personal fees from Daiichi Sankyo, personal fees from Bayer Pharma AG, personal fees from Jazz Pharmaceuticals, personal fees from BMS, personal fees from Tolremo, outside the submitted work. BK has received honoraria for lectures from Ipsen, Novartis and MSD (all outside of the submitted work). J-JK reports consulting fees and honoraria from Novartis, consulting fees from AbbVie, honoraria from AOP Orphan Pharma, participation on a monitoring board or advisory board from BMS/Celgene, participation on a monitoring board or advisory board from Incyte. NK reports grants and honoraria from Neovii, honoraria from Sanofi, grants and honoraria from Jazz, grants and honoraria from Celgene, grants and honoraria from Riemser, honoraria from Gilead/Kite, honorarium from AOP Oprhan Pharma, grants and honorarium from Novartis, honorarium from Amgen. PM reports personal fees from Celgene, Amgen, Janssen, AbbVie, Sanofi, outside the submitted work. JP has declared no conflicts of interest. FP has declared no conflicts of interest. DR received honoraria from Incyte, Novartis Pharma, Pfizer; clinical trial steering committee membership: Novartis; membership on advisory boards: Incyte, Novartis Pharma, Pfizer. J-MR reports grants and honoraria from Novartis, Amgen, Pfizer, Takeda, Incyte, and Servier. TR has declared no conflicts of interest. JF-M reports consulting and advisory boards honoraria (received by CUN) from AbbVie, Amgen, BMS, Celgene, Janssen, GlaxoSmithKline, Karyopharm, MSD, Novartis, Takeda, Sanofi, SecuraBio, Regeneron, Roche, outside the submitted work. VS has declared no conflicts of interest. GFS reports personal fees and other from AbbVie, other from Amgen, other from Astellas, other from Boehringer-Ingelheim, grants, personal fees and other from Celgene, other from Helsinn Healthcare, grants, personal fees, and other from Janssen-Cilag, grants and other from Novartis, other from Onconova, grants, personal fees and other from Roche, and other from Takeda, outside the submitted work. PS reports honoraria from Amgen, Celgene, Janssen, Karyopharm, SkylineDx, Takeda, and research support from Celgene, Janssen, Amgen, Takeda, BMS, SkylineDx, Karyopharm, all outside the submitted work. MvL-T has received travel grants and honoraria from Celgene, Gilead, Chugai, Janssen, Novartis, Amgen, Takeda, BMS, Medac, Oncopeptides, Merck, CDDF, Pfizer, Medac, Thermo Fisher, AstraZeneca; is a consultant for Celgene, Gilead, Oncopeptides, MSD, 4D Pharma, Janssen, Shionogi and received research funding from BMBF, Deutsche Jose Carreras Leukämie-Stiftung, IZKF Jena, Novartis, Gilead, Deutsche Krebshilfe, Celgene, Oncopeptides, Deutsche Forschungsgemeinschaft (DFG). CW has declared no conflicts of interest. GP reports grants from Amgen, grants, personal fees and non-financial support from Merck, grants and non-financial support from AstraZeneca, grants and personal fees from Roche, grants and personal fees from BMS, grants from Lilly, grants and personal fees from MSD, grants and personal fees from Novartis, outside the submitted work. FP reports grants from Novartis, Celgene, BMS, Abbvie, Karyopharma, Janssen. GP reports grants from Amgen, grants, personal fees and non-financial support from Merck, grants and non-financial support from AstraZeneca, grants and personal fees from Roche, grants and personal fees from BMS, grants from Lilly, grants and personal fees from MSD, grants and personal fees from Novartis, outside the submitted work. Background: The COVID-19 pandemic has created enormous challenges for the clinical management of patients with hematological malignancies (HMs), raising questions about the optimal care of this patient group. Methods: This consensus manuscript aims at discussing clinical evidence and providing expert advice on statements related to the management of HMs in the COVID-19 pandemic. For this purpose, an international consortium was established including a steering committee, which prepared six working packages addressing significant clinical questions from the COVID-19 diagnosis, treatment, and mitigation strategies to specific HMs management in the pandemic. During a virtual consensus meeting, including global experts and lead by the European Society for Medical Oncology and the European Hematology Association, statements were discussed and voted upon. When a consensus could not be reached, the panel revised statements to develop consensual clinical guidance. Results and conclusion: The expert panel agreed on 33 statements, reflecting a consensus, which will guide clinical decision making for patients with hematological neoplasms during the COVID-19 pandemic.
Published: 2022
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29. Nestin as a diagnostic and prognostic marker for combined hepatocellular-cholangiocarcinoma

Author: Julien Calderaro, Luca Di Tommaso, Pascale Maillé, Aurélie Beaufrère, Cong Trung Nguyen, Lara Heij, Viviane Gnemmi, Rondell P. Graham, Frédéric Charlotte, Suzanne Chartier, Dominique Wendum, Mukul Vij, Daniela Allende, Alba Diaz, Carla Fuster, Benjamin Rivière, Astrid Herrero, Jérémy Augustin, Katja Evert, Diego Francesco Calvisi, Wei Qiang Leow, Howard Ho Wai Leung, Jan Bednarsch, Emmanuel Boleslawski, Mohamed Rela, Anthony Wing-Hung Chan, Alejandro Forner, Maria Reig, Anaïs Pujals, Loetitia Favre, Manon Allaire, Olivier Scatton, Arnaud Uguen, Eric Trépo, Lukas Otero Sanchez, Denis Chatelain, Myriam Remmelink, Camille Boulagnon-Rombi, Céline Bazille, Nathalie Sturm, Benjamin Menahem, Eric Frouin, David Tougeron, Christophe Tournigand, Emmanuelle Kempf, Haeryoung Kim, Massih Ningarhari, Sophie Michalak-Provost, Jakob Nikolas Kather, Annette S.H. Gouw, Purva Gopal, Raffaele Brustia, Eric Vibert, Kornelius Schulze, Darius F. Rüther, Sören A. Weidemann, Rami Rhaiem, Jean-Charles Nault, Alexis Laurent, Giuliana Amaddeo, Hélène Regnault, Eleonora de Martin, Christine Sempoux, Pooja Navale, Jayendra Shinde, Ketan Bacchuwar, Maria Westerhoff, Regina Cheuk-Lam Lo, Mylène Sebbagh, Catherine Guettier, Marie Lequoy, Mina Komuta, Marianne Ziol, Valérie Paradis, Jeanne Shen, Stefano Caruso, Hôpital Henri Mondor, Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Pathologie [Hôpital Beaujon - APHP], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Molecular virology and immunology – Physiopathology and therapeutic of chronic viral hepatitis (Team 18) (Inserm U955), 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), Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), CHU Lille, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), 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), University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), 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], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Université libre de Bruxelles (ULB), CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 (CHIMERE), Université de Picardie Jules Verne (UPJV), Laboratoire de Signalisation et Récepteurs Matriciels (SiRMa), Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS)-Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Département de Pathologie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Grenoble, Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Chirurgie Viscérale et Digestive [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé (LIMICS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Sorbonne Paris Nord, Groupe Henri Mondor-Albert Chenevier, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Johns Hopkins University (JHU), Hôpital Claude Huriez [Lille], Physiopathologie et traitement des maladies du foie, Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Centre Hospitalier Universitaire de Reims (CHU Reims), Génomique fonctionnelle des tumeurs solides = Functional Genomics of Solid Tumors [CRC] (FunGeST), 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)-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), Labex OncoImmunology, Equipe labellisée Ligue Contre le Cancer, Université Paris Descartes - Paris 5 (UPD5), Service d'Hépatologie [Avicenne], Hôpital Avicenne [AP-HP], Unité de Formation et de Recherche Santé, Médecine, Biologie Humaine [Bobigny], Université Paris 13 (UP13)-Sorbonne Paris Cité, Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Crosscope, University of Michigan [Ann Arbor], University of Michigan System, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Hôpital Bicêtre, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d’Anatomie Pathologique [CHU Beaujon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP], Labex Immuno-oncology [Paris] ( Université Paris Descartes - Paris 5 - PRES Sorbonne Paris Cité), Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité, Service d'Anatomie et cytologie pathologiques [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Anatomie et cytologie pathologiques = Service de Pathologie [CHU Pitié-Salpêtrière] (ACP), CHU Henri Mondor, Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École pratique des hautes études (EPHE), Service d'Hépato-gastro-entérologie [CHU Saint-Antoine], and Groningen Institute for Organ Transplantation (GIOT)
Subjects: Carcinoma, Hepatocellular, Hepatology, combined hepatocellular-cholangiocarcinoma, Liver Neoplasms, hepatocellular carcinoma, liver, Prognosis, Nestin, Cholangiocarcinoma, Bile Ducts, Intrahepatic, Bile Duct Neoplasms, cancer, Humans, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background & Aims: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer (PLC) associated with a poor prognosis. Given the challenges in its identification and its clinical implications, biomarkers are critically needed. We aimed to investigate the diagnostic and prognostic value of the immunohistochemical expression of Nestin, a progenitor cell marker, in a large multicentric series of PLCs.Methods: We collected 461 cHCC-CCA samples from 32 different clinical centers. Control cases included 368 hepatocellular carcinomas (HCCs) and 221 intrahepatic cholangiocarcinomas (iCCAs). Nestin immunohistochemistry was performed on whole tumor sections. Diagnostic and prognostic performances of Nestin expression were determined using receiver-operating characteristic curves and Cox regression modeling.Results: Nestin was able to distinguish cHCC-CCA from HCC with AUCs of 0.85 and 0.86 on surgical and biopsy samples, respectively. Performance was lower for the distinction of cHCC-CCA from iCCA (AUCs of 0.59 and 0.60). Nestin, however, showed a high prognostic value, allowing identification of the subset of cHCC-CCA (“Nestin High”, >30% neoplastic cells with positive staining) associated with the worst clinical outcome (shorter disease-free and overall survival) after surgical resection and liver transplantation, as well as when assessment was performed on biopsies.Conclusion: We show in different clinical settings that Nestin has diagnostic value and that it is a useful biomarker to identify the subset of cHCC-CCA associated with the worst clinical outcome. Nestin immunohistochemistry may be used to refine risk stratification and improve treatment allocation for patients with this highly aggressive malignancy. Lay summary: There are different types of primary liver cancers (i.e. cancers that originate in the liver). Accurately identifying a specific subtype of primary liver cancer (and determining its associated prognosis) is important as it can have a major impact on treatment allocation. Herein, we show that a protein called Nestin could be used to refine risk stratification and improve treatment allocation for patients with combined hepatocellular carcinoma, a rare but highly aggressive subtype of primary liver cancer.
Published: 2021
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30. Phase Ib/II study of ceritinib in combination with ribociclib in patients with ALK-rearranged non-small cell lung cancer

Author: Armando Santoro, Wu-Chou Su, Alejandro Navarro, Matteo Simonelli, James CH Yang, Andrea Ardizzoni, Fabrice Barlesi, Jin Hyoung Kang, Sarah DiDominick, Ahmed Abdelhady, Xueying Chen, Uz Stammberger, Enriqueta Felip, Institut Català de la Salut, [Santoro A, Simonelli M] Department of Biomedical Sciences, Humanitas University, Milan, Italy. IRCCS Humanitas Research Hospital–Humanitas Cancer Center, Milan, Italy. [Su WC] Department of Oncology, National Cheng Kung University Hospital, Tainan, Taiwan. [Navarro A, Felip E] Servei d’Oncologia Mèdica, Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Yang JCH] National Taiwan University Cancer Center, Taipei, Taiwan. [Ardizzoni A] IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy, Vall d'Hebron Barcelona Hospital Campus, Vall d'Hebron Institute of Oncology [Barcelone] (VHIO), Vall d'Hebron University Hospital [Barcelona], Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), 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), and Institut Gustave Roussy (IGR)
Subjects: Pulmonary and Respiratory Medicine, Adult, Cancer Research, Lung Neoplasms, [SDV]Life Sciences [q-bio], Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Aminopyridines, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Otros calificadores::Otros calificadores::/efectos adversos [Otros calificadores], Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protein Kinase Inhibitors [CHEMICALS AND DRUGS], Carcinoma, Non-Small-Cell Lung, Other subheadings::Other subheadings::/adverse effects [Other subheadings], Humans, Anaplastic Lymphoma Kinase, Sulfones, Protein Kinase Inhibitors, acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::inhibidores enzimáticos::inhibidores de proteínas cinasas [COMPUESTOS QUÍMICOS Y DROGAS], Receptor Protein-Tyrosine Kinases, Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms::Bronchial Neoplasms::Carcinoma, Bronchogenic::Carcinoma, Non-Small-Cell Lung [DISEASES], neoplasias::neoplasias por localización::neoplasias torácicas::neoplasias del tracto respiratorio::neoplasias pulmonares::neoplasias de los bronquios::carcinoma broncogénico::carcinoma de pulmón de células no pequeñas [ENFERMEDADES], Middle Aged, Proteïnes quinases - Inhibidors, Pyrimidines, Oncology, Purines, Pulmons - Càncer - Tractament
Abstract: ALK inhibitors; Ceritinib; Ribociclib Inhibidores de ALK; Ceritinib; Ribociclib Inhibidors d'ALK; Ceritinib; Ribociclib Background Preclinical data show that the combination of an ALK inhibitor (ALKi) with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) may act synergistically to overcome drug resistance mechanisms. Here, we assessed the safety, tolerability, and preliminary clinical activity of ceritinib, an ALKi in combination with ribociclib, a CDK4/6i, in patients with ALK-rearranged non–small cell lung cancer (NSCLC). Methods This was a multicenter, open-label, phase Ib/II dose-escalation study to determine the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) for ceritinib plus ribociclib therapy. Results Twenty-seven adult patients with ALK-rearranged advanced NSCLC with an ECOG PS ≤ 2 were enrolled into five cohorts to receive various dose combinations of ceritinib (range, 300–450 mg/day) and ribociclib (range, 100–300 mg/day). Median age of patients was 57 years. MTDs were not reached in this study. Enrollment into phase Ib was terminated early and phase II was not opened due to changes in the ALK-rearranged NSCLC treatment landscape. Ceritinib 300 mg/day and ribociclib 200 mg/day (3-weeks-on/1-week-off schedule) was identified as the RP2D. Among the 27 evaluable patients, the overall response rate (ORR) was 37.0% (95% CI, 19.4–57.6) and median progression-free survival (mPFS) was 21.5 months (95% CI, 5.5–25.0). At RP2D, the ORR was 50.0%, disease control rate was 75%, and mPFS was 24.8 months (95% CI, 5.5–25.1). Safety profile of the combination therapy was consistent with single-agent safety data. Conclusion Combination of ceritinib and ribociclib showed clinical activity with a manageable safety profile in patients with advanced ALK-rearranged NSCLC. This study was supported by Novartis Pharmaceuticals Corporation.
Published: 2021
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31. WAO-ARIA consensus on chronic cough – Part 1

Author: Philip W. Rouadi, Samar A. Idriss, Jean Bousquet, Tanya M. Laidlaw, Cecilio R. Azar, Mona Sulaiman AL-Ahmad, Anahí Yáñez, Maryam Ali Y. AL-Nesf, Talal M. Nsouli, Sami L. Bahna, Eliane Abou-Jaoude, Fares H. Zaitoun, Usamah M. Hadi, Peter W. Hellings, Glenis K. Scadding, Peter K. Smith, Mario Morais-Almeida, R. Maximiliano Gómez, Sandra N. González Díaz, Ludger Klimek, Georges S. Juvelekian, Moussa A. Riachy, Giorgio Walter Canonica, David Peden, Gary W.K. Wong, James Sublett, Jonathan A. Bernstein, Lianglu Wang, Luciana Kase Tanno, Manana Chikhladze, Michael Levin, Yoon-Seok Chang, Bryan L. Martin, Luis Caraballo, Adnan Custovic, José Antonio Ortega-Martell, Erika Jensen-Jarolim, Motohiro Ebisawa, Alessandro Fiocchi, Ignacio J. Ansotegui, Salvy-Córdoba, Nathalie, Beirut Eye & ENT Specialist Hospital (BESH), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Berlin Institute of Health (BIH), 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), Université de Montpellier (UM), Brigham and Women’s Hospital [Boston, MA], Harvard Medical School [Boston] (HMS), American University of Beirut Faculty of Medicine and Medical Center (AUB), Middle East Institute of Health, Clemenceau Medical Center (CMC), Kuwait University, Investigaciones en Alergia y Enfermedades Respiratorias (InAER), Hamad Medical Corporation [Doha, Qatar], International Cough Institute (ICI), Louisiana State University (LSU), LAU Medical Center-Rizk Hospital, VIB-KU Leuven Center for Microbiology [Leuven, Belgium], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University Hospitals Leuven [Leuven], Ghent University Hospital, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), The Royal National TNE Hospital, University College of London [London] (UCL), Griffith University [Brisbane], Hospital CUF Descobertas, Catholic University of Salta, Universidad Autonoma de Nuevo Leon [Mexique] (UANL), Center for Rhinology and Allergology Wiesbaden, University Hospital Mannheim, Saint George Hospital University Medical Center [UOB LIBAN], University of Balamand [Liban] (UOB), Hôtel-Dieu de France (HDF), Université Saint-Joseph de Beyrouth (USJ), Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), The Chinese University of Hong Kong [Hong Kong], University of Louisville School of Medicine, University of Cincinnati College of Medicine, Peking Union Medical College Hospital [Beijing] (PUMCH), Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Akaki Tsereteli State University, University of Cape Town, Seoul National University Hospital, The Ohio State University Wexner Medical Center., University of Cartagena, Imperial College London, Universidad Autónoma del Estado de Hidalgo (UAEH), Medizinische Universität Wien = Medical University of Vienna, Messerli Research Institute, University of Veterinary Medicine Vienna, Medical University Vienna, University of Vienna [Vienna]-University of Vienna [Vienna]-Medical University Vienna, University of Vienna [Vienna]-University of Vienna [Vienna], Sagamihara National Hospital [Kanagawa, Japan], Bambino Gesù Children’s Hospital [Rome, Italy], and Hospital Quirónsalud Bizkaia [Bilbao]
Subjects: Pulmonary and Respiratory Medicine, Allergy, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immunology, INDUCED ENHANCEMENT, ION-CHANNEL, Pathogenesis, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Article, PAIN HYPERSENSITIVITY, HYPERSENSITIVITY SYNDROME, CENTRAL SENSITIZATION, Chronic cough, TRP channel, Immunology and Allergy, Science & Technology, THERAPEUTIC TARGET, Chemoreceptors, RECEPTOR SUBTYPES, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, RC581-607, GENE-RELATED PEPTIDE, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, respiratory tract diseases, P2X3, DISTINCT POPULATIONS, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, [SDV.IMM]Life Sciences [q-bio]/Immunology, CENTRAL MECHANISMS, Immunologic diseases. Allergy, Life Sciences & Biomedicine, Mechanoreceptors
Abstract: BACKGROUND: Cough features a complex peripheral and central neuronal network. The function of the chemosensitive and stretch (afferent) cough receptors is well described but partly understood. It is speculated that chronic cough reflects a neurogenic inflammation of the cough reflex, which becomes hypersensitive. This is mediated by neuromediators, cytokines, inflammatory cells, and a differential expression of neuronal (chemo/stretch) receptors, such as transient receptor potential (TRP) and purinergic P2X ion channels; yet the overall interaction of these mediators in neurogenic inflammation of cough pathways remains unclear. OBJECTIVES: The World Allergy Organization/Allergic Rhinitis and its Impact on Asthma (WAO/ARIA) Joint Committee on Chronic Cough reviewed the current literature on neuroanatomy and pathophysiology of chronic cough. The role of TRP ion channels in pathogenic mechanisms of the hypersensitive cough reflex was also examined. OUTCOMES: Chemoreceptors are better studied in cough neuronal pathways compared to stretch receptors, likely due to their anatomical overabundance in the respiratory tract, but also their distinctive functional properties. Central pathways are important in suppressive mechanisms and behavioral/affective aspects of chronic cough. Current evidence strongly suggests neurogenic inflammation induces a hypersensitive cough reflex marked by increased expression of neuromediators, mast cells, and eosinophils, among others. TRP ion channels, mainly TRP V1/A1, are important in the pathogenesis of chronic cough due to their role in mediating chemosensitivity to various endogenous and exogenous triggers, as well as a crosstalk between neurogenic and inflammatory pathways in cough-associated airways diseases. ispartof: WORLD ALLERGY ORGANIZATION JOURNAL vol:14 issue:12 ispartof: location:United States status: published
Published: 2021
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32. Management and outcomes in critically ill nonagenarian versus octogenarian patients

Author: Bruno, Raphael Romano, Wernly, Bernhard, Kelm, Malte, Boumendil, Ariane, Morandi, Alessandro, Andersen, Finn H., Artigas, Antonio, Finazzi, Stefano, Cecconi, Maurizio, Christensen, Steffen, Faraldi, Loredana, Lichtenauer, Michael, Muessig, Johanna M., Marsh, Brian, Moreno, Rui, Oeyen, Sandra, Öhman, Christina Agvald, Pinto, Bernardo Bollen, Soliman, Ivo W., Szczeklik, Wojciech, Valentin, Andreas, Watson, Ximena, Leaver, Susannah, Boulanger, Carole, Walther, Sten, Schefold, Joerg C., Joannidis, Michael, Nalapko, Yuriy, Elhadi, Muhammed, Fjølner, Jesper, Zafeiridis, Tilemachos, De Lange, Dylan W., Guidet, Bertrand, Flaatten, Hans, Jung, Christian, Eller, Philipp, Helbok, Raimund, Schmutz, René, Nollet, Joke, de Neve, Nikolaas, Buysscher, Pieter De, Swinnen, Walter, Mikačić, Marijana, Bastiansen, Anders, Husted, Andreas, Dahle, Bård E.S., Cramer, Christine, Sølling, Christoffer, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Karolinska Institutet [Stockholm], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), the Handmaids of Charity Nursing Home / Casa di Cura Ancelle della Carità [Cremona, Italia], NTNU [Ålesund], Hospital Universitari Parc Taulí [Sabadell, Spain] (HUPT), CIBER de Epidemiología y Salud Pública (CIBERESP), RCCS–Istituto di Ricerche Farmacologiche 'Mario Negri [Bergamo, Italy], Clinical Research Center for Rare Diseases 'Aldo e Cele Daccò' [Bergamo, Italy], Humanitas University [Milan] (Hunimed), Aarhus University Hospital, ASST Great Metropolitan Niguarda / ASST Grande Ospedale Metropolitano Niguarda [Milan, Italia], Mater Misericordiae University Hospital (The Mater Hospital), NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Ghent University Hospital, Karolinska University Hospital [Stockholm], Geneva University Hospitals and Geneva University, Utrecht University [Utrecht], Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Cardinal Schwarzenberg Hospital [Pongau, Austria] (CSH), St George’s University Hospitals, Royal Devon and Exeter NHS Foundation Trust [UK], Linköping university hospital, University of Bern, Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), European Wellness International [Luhansk, Ukraine] (EWI), Alkhums Hospital [Tripoli, Libya] (AH), University Hospital of Larissa, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), University of Bergen (UiB), Haukeland University Hospital, VIP2 study group: Michael Joannidis, Philipp Eller, Raimund Helbok, René Schmutz, Joke Nollet, Nikolaas de Neve, Pieter De Buysscher, Sandra Oeyen, Walter Swinnen, Marijana Mikačić, Anders Bastiansen, Andreas Husted, Bård E S Dahle, Christine Cramer, Christoffer Sølling, Dorthe Ørsnes, Jakob Edelberg Thomsen, Jonas Juul Pedersen, Mathilde Hummelmose Enevoldsen, Thomas Elkmann, Agnieszka Kubisz-Pudelko, Alan Pope, Amy Collins, Ashok S Raj, Carole Boulanger, Christian Frey, Ciaran Hart, Clare Bolger, Dominic Spray, Georgina Randell, Helder Filipe, Ingeborg D Welters, Irina Grecu, Jane Evans, Jason Cupitt, Jenny Lord, Jeremy Henning, Joanne Jones, Jonathan Ball, Julie North, Kiran Salaunkey, Laura Ortiz-Ruiz De Gordoa, Louise Bell, Madhu Balasubramaniam, Marcela Vizcaychipi, Maria Faulkner, Mc Donald Mupudzi, Megan Lea-Hagerty, Michael Reay, Michael Spivey, Nicholas Love, Nick Spittle Nick Spittle, Nigel White, Patricia Williams, Patrick Morgan, Phillipa Wakefield, Rachel Savine, Reni Jacob, Richard Innes, Ritoo Kapoor, Sally Humphreys, Steve Rose, Susan Dowling, Susannah Leaver, Tarkeshwari Mane, Tom Lawton, Vongayi Ogbeide, Waqas Khaliq, Yolanda Baird, Antoine Romen, Arnaud Galbois, Bertrand Guidet, Christophe Vinsonneau, Cyril Charron, Didier Thevenin, Emmanuel Guerot, Guillaume Besch, Guillaume Savary, Hervé Mentec, Jean-Luc Chagnon, Jean-Philippe Rigaud, Jean-Pierre Quenot, Jeremy Castanera, Jérémy Rosman, Julien Maizel, Kelly Tiercelet, Lucie Vettoretti, Maud Mousset Hovaere, Messika Messika, Michel Djibré, Nathalie Rolin, Philippe Burtin, Pierre Garcon, Saad Nseir, Xavier Valette, Christian Rabe, Eberhard Barth, Henning Ebelt, Kristina Fuest, Marcus Franz, Michael Horacek, Michael Schuster, Patrick Meybohm, Raphael Romano Bruno, Sebastian Allgäuer, Simon Dubler, Stefan J Schaller, Stefan Schering, Stephan Steiner, Thorben Dieck, Tim Rahmel, Tobias Graf, Anastasia Koutsikou, Aristeidis Vakalos, Bogdan Raitsiou, Elli Niki Flioni, Evangelia Neou, Fotios Tsimpoukas, Georgios Papathanakos, Giorgos Marinakis, Ioannis Koutsodimitropoulos, Kounougeri Aikaterini, Nikoletta Rovina, Stylliani Kourelea, Polychronis Tasioudis, Vasiiios Zidianakis, Vryza Konstantinia, Zoi Aidoni, Brian Marsh, Catherine Motherway, Chris Read, Ignacio Martin-Loeches, Andrea Neville Cracchiolo, Aristide Morigi, Italo Calamai, Stefania Brusa, Ahmed Elhadi, Ahmed Tarek, Ala Khaled, Hazem Ahmed, Wesal Ali Belkhair, Alexander D Cornet, Diederik Gommers, Dylan W De Lange, Eva van Boven, Jasper Haringman, Lenneke Haas, Lettie van den Berg, Oscar Hoiting, Peter de Jager, Rik T Gerritsen, Tom Dormans, Willem Dieperink, Alena Breidablik Alena Breidablik, Anita Slapgard, Anne-Karin Rime, Bente Jannestad, Britt Sjøbøe, Eva Rice, Finn H Andersen, Hans Frank Strietzel, Jan Peter Jensen, Jørund Langørgen, Kirsti Tøien, Kristian Strand, Michael Hahn, Pål Klepstad, Aleksandra Biernacka, Anna Kluzik, Bartosz Kudlinski, Dariusz Maciejewski, Dorota Studzińska, Hubert Hymczak, Jan Stefaniak, Joanna Solek-Pastuszka, Joanna Zorska, Katarzyna Cwyl, Lukasz J Krzych, Maciej Zukowski, Małgorzata Lipińska-Gediga, Marek Pietruszko, Mariusz Piechota, Marta Serwa, Miroslaw Czuczwar, Mirosław Ziętkiewicz, Natalia Kozera, Paweł Nasiłowski, Paweł Sendur, Paweł Zatorski, Piotr Galkin, Ryszard Gawda, Urszula Kościuczuk, Waldemar Cyrankiewicz, Wojciech Gola, Alexandre Fernandes Pinto, Ana Margarida Fernandes, Ana Rita Santos, Cristina Sousa, Inês Barros, Isabel Amorim Ferreira, Jacobo Bacariza Blanco, João Teles Carvalho, Jose Maia, Nuno Candeias, Nuno Catorze, Vladislav Belskiy, Africa Lores, Angela Prado Mira, Catia Cilloniz, David Perez-Torres, Emilio Maseda, Enver Rodriguez, Estefania Prol-Silva, Gaspar Eixarch, Gemma Gomà, Gerardo Aguilar, Gonzalo Navarro Velasco, Marián Irazábal Jaimes, Mercedes Ibarz Villamayor, Noemí Llamas Fernández, Patricia Jimeno Cubero, Sonia López-Cuenca, Teresa Tomasa, Anders Sjöqvist, Camilla Brorsson, Fredrik Schiöler, Henrik Westberg, Jessica Nauska, Joakim Sivik, Johan Berkius, Karin Kleiven Thiringer, Lina De Geer, Sten Walther, Filippo Boroli, Joerg C Schefold, Leila Hergafi, Philippe Eckert, Ismail Yıldız, Ihor Yovenko, Yuriy Nalapko, Richard Pugh, Malbec, Odile, Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), Mater Misericordiae University Hospital [Dublin] (The Mater Hospital), Jagiellonian University Medical College / Uniwersytet Jagielloński Collegium Medicum [Krakow, Poland], Innsbruck Medical University [Austria] (IMU), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM), and Intensive Care
Subjects: Aged, 80 and over, Octogenarians, Critical Care, Frailty, Omvårdnad, Research, Critical Illness, [SDV]Life Sciences [q-bio], 610 Medicine & health, Nursing, Cohort Studies, Hospitalization, [SDV] Life Sciences [q-bio], Critical Illness/therapy, Nonagenarians, Humans, Intensive care medicine, Geriatrics and Gerontology, Outcome
Abstract: Funding Information: This study was endorsed by the ESICM. Free support for running the electronic database and was granted from the dep. of Epidemiology, University of Aarhus, Denmark. Financial support for creation of the e-CRF and maintenance of the database was possible from a grant (open project support) by Western Health region in Norway) 2018 who also funded the participating Norwegian ICUs. DRC Ile de France and URC Est helped conducting VIP2 in France. Open Access funding enabled and organized by Projekt DEAL. Publisher Copyright: © 2021, The Author(s). Background: Intensive care unit (ICU) patients age 90 years or older represent a growing subgroup and place a huge financial burden on health care resources despite the benefit being unclear. This leads to ethical problems. The present investigation assessed the differences in outcome between nonagenarian and octogenarian ICU patients. Methods: We included 7900 acutely admitted older critically ill patients from two large, multinational studies. The primary outcome was 30-day-mortality, and the secondary outcome was ICU-mortality. Baseline characteristics consisted of frailty assessed by the Clinical Frailty Scale (CFS), ICU-management, and outcomes were compared between octogenarian (80–89.9 years) and nonagenarian (> 90 years) patients. We used multilevel logistic regression to evaluate differences between octogenarians and nonagenarians. Results: The nonagenarians were 10% of the entire cohort. They experienced a higher percentage of frailty (58% vs 42%; p < 0.001), but lower SOFA scores at admission (6 + 5 vs. 7 + 6; p < 0.001). ICU-management strategies were different. Octogenarians required higher rates of organ support and nonagenarians received higher rates of life-sustaining treatment limitations (40% vs. 33%; p < 0.001). ICU mortality was comparable (27% vs. 27%; p = 0.973) but a higher 30-day-mortality (45% vs. 40%; p = 0.029) was seen in the nonagenarians. After multivariable adjustment nonagenarians had no significantly increased risk for 30-day-mortality (aOR 1.25 (95% CI 0.90–1.74; p = 0.19)). Conclusion: After adjustment for confounders, nonagenarians demonstrated no higher 30-day mortality than octogenarian patients. In this study, being age 90 years or more is no particular risk factor for an adverse outcome. This should be considered– together with illness severity and pre-existing functional capacity - to effectively guide triage decisions. Trial registration: NCT03134807 and NCT03370692. publishersversion published
Published: 2021
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33. Steroid use in elderly critically ill COVID-19 patients

Author: Wojciech Szczeklik, Hans Flaatten, Michael Joannidis, Mirosław Czuczwar, Christian Jung, Michael Beil, Raphael Romano Bruno, Jesper Fjølner, Tilemachos Zafeiridis, Rui Moreno, Sviri Sigal, Bernardo Bollen Pinto, Bernhard Wernly, Peter Vernon van Heerden, Muhammed Elhadi, Antonio Artigas, David M. Dudzinski, Georg Wolff, Susannah Leaver, Finn H. Andersen, Brian Marsh, Sandra Oeyen, Dylan W. de Lange, Malte Kelm, Joerg C. Schefold, Ariane Boumendil, Maurizio Cecconi, Bertrand Guidet, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Aarhus University Hospital, Massachusetts General Hospital [Boston], Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), Geneva University Hospitals and Geneva University, University of Bern, The Hebrew University of Jerusalem (HUJ), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Medical University of Lublin, University of Tripoli - University Al Fateh, Innsbruck Medical University [Austria] (IMU), Ghent University Hospital, University Hospital of Larissa, Mater Misericordiae University Hospital [Dublin] (The Mater Hospital), Aalesund University College, Norwegian University of Science and Technology [Trondheim] (NTNU), Norwegian University of Science and Technology (NTNU), NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Humanitas University [Milan] (Hunimed), St George’s University Hospitals, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Réanimation Médicale [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Utrecht University [Utrecht], University of Bergen (UiB), Haukeland University Hospital, NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM), HAL-SU, Gestionnaire, Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Mater Misericordiae University Hospital (The Mater Hospital), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), viruses, Critical Illness, MEDLINE, 610 Medicine & health, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, MESH: Risk Factors, Secondary analysis, Medicine and Health Sciences, medicine, Research Letter, Humans, MESH: COVID-19, MESH: SARS-CoV-2, 030212 general & internal medicine, Intensive care medicine, skin and connective tissue diseases, ComputingMilieux_MISCELLANEOUS, Aged, MESH: Aged, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, MESH: Humans, business.industry, Critically ill, SARS-CoV-2, fungi, COVID-19, MESH: Steroids, 3. Good health, respiratory tract diseases, body regions, 030228 respiratory system, Steroid use, MESH: Critical Illness, Steroids, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: More than a year after the onset of the SARS-Cov-2 pandemic, treating patients with COVID-19 remains a challenge. By contrast to the rapid development of effective vaccines against SARS-Cov-2, the development of specific and effective therapeutics against COVID-19 remains largely unresolved., This secondary analysis of the COVIP study shows a higher 30-day-mortality in critically ill elderly COVID-19 patients who received steroids as part of their treatment.
Published: 2021
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34. 3TR

Author: Heribert Staudinger, Judith Axmann, Maarten van den Berge, Sven-Erik Dahlén, Liam G Heaney, Franca Rusconi, Rekha Chaudhuri, Anke H. Maitland-van der Zee, Valeria Ramiconi, Guy Brusselle, Maciej Kupczyk, Piotr Kuna, Rosa Faner, Marc P. van der Schee, Claus Vogelmeier, Giorgio Walter Canonica, Kian Fan Chung, Arnaud Bourdin, Ratko Djukanovic, Sejla Saglani, Celeste Porsbjerg, Graham W. Clarke, Graham Roberts, Courtney Coleman, Jadwiga A. Wedzicha, Charles Pilette, Martijn C. Nawijn, Alvar Agusti, Christopher E. Brightling, Bispebjerg University Hospital, University of Amsterdam [Amsterdam] (UvA), Ghent University Hospital, IRCCS Humanitas [Rozzano, Italy], Humanitas University [Milan] (Hunimed), University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Philipps University of Marburg, German Center for Lung Research, University of Groningen [Groningen], Children's Hospital A. Meyer-University of Florence, Université Catholique de Louvain = Catholic University of Louvain (UCL), European Federation of Allergy and Airways Diseases Patients' Associations (EFA), The European Lung Foundation (ELF), University of Glasgow, Imperial College London, Royal Brompton Hospital, Queen's University [Belfast] (QUB), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), University of Southampton, University Hospital Southampton NHS Foundation Trust, The David Hide Asthma and Allergy Research Centre, St Mary's Hospital-University Hospital Southampton NHS Foundation Trust, NIHR Southampton Biomedical Research Centre, Medical University of Łódź (MUL), Roche Pharma Research and Early Development [Basel] (pRED), F. Hoffmann-La Roche [Basel], Sanofi Genzyme, AstraZeneca, Gothenburg, Sweden, Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], University of Leicester, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, UCL - (SLuc) Centre de l'allergie, UCL - (SLuc) Service de pneumologie, Philipps Universität Marburg = Philipps University of Marburg, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), MORNET, Dominique, and Groningen Research Institute for Asthma and COPD (GRIAC)
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, [SDV]Life Sciences [q-bio], education, Disease, Pulmonary Disease, 03 medical and health sciences, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Pan european, medicine, Immune Diseases, Humans, Intensive care medicine, ComputingMilieux_MISCELLANEOUS, Asthma, COPD, Asthma/drug therapy, business.industry, 030503 health policy & services, biochemical phenomena, metabolism, and nutrition, medicine.disease, Pulmonary Disease, Chronic Obstructive/drug therapy, humanities, 3. Good health, respiratory tract diseases, [SDV] Life Sciences [q-bio], Cross-Sectional Studies, 030228 respiratory system, Chronic Obstructive/drug therapy, bacteria, 0305 other medical science, business
Abstract: The 3TR (Taxonomy, Treatments, Targets and Remission) consortium is the largest IMI (Innovative Medicine Initiative) project ever started in the field of immune diseases (https://3tr-imi.eu/). 3TR is unique in bringing several medical specialties, encompassing respiratory medicine, rheumatology, neurology and gastroenterology, together, to study disease mechanisms across seven disease entities: asthma, COPD, systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, ulcerative colitis and Crohn's disease. [...]
Published: 2021
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35. Allogeneic transplantation after PD-1 blockade for classic Hodgkin lymphoma

Author: Didier Blaise, Tycel Phillips, Jason T. Romancik, Roch Houot, Robert Lowsky, Martina Sollini, Jean Marc Schiano De Colella, Amer Beitinjaneh, Gunjan L. Shah, Lazaros J. Lekakis, Stephen D. Smith, Paolo Corradini, Mohamad Mohty, Maryam Rahimian, Luca Castagna, Taiga Nishihori, Asad Bashey, Talha Badar, Reid W. Merryman, Mehdi Hamadani, Carmelo Carlo-Stella, Dipenkumar Modi, Sally Arai, Kamal Bouabdallah, Valter Torri, Joseph P. McGuirk, Guillaume Manson, Anna Guidetti, Yi-Bin Chen, Hatcher J. Ballard, Julio C. Chavez, Pier Luigi Zinzani, Tatyana Feldman, Sunita Nathan, Anurag K. Singh, Massimo Magagnoli, Marie Pierre Moles-Moreau, Beatrice Casadei, Anthony Serritella, Michael Byrne, Radhakrishnan Ramchandren, Miguel-Angel Perales, Chiara De Philippis, Samantha Jaglowski, Justin Kline, Remy Dulery, Laura Giordano, Alex F. Herrera, Jonathon B. Cohen, Philippe Armand, Armando Santoro, Aspasia Stamatoulas, Stephen M. Ansell, Michael A. Spinner, Lori Dahncke, Corentin Orvain, Chloé Spilleboudt, Geoffrey Shouse, Robin Joyce, Vincent T. Ho, Matthew J. Frigault, Ryan C. Lynch, Uttam Rao, Jakub Svoboda, David A. Bond, Yago Nieto, Dana-Farber Cancer Institute [Boston], Humanitas Clinical and Research Center [Rozzano, Milan, Italy], Università degli Studi di Milano = University of Milan (UNIMI), University of Bologna/Università di Bologna, Ohio State University [Columbus] (OSU), Stanford University, Memorial Sloane Kettering Cancer Center [New York], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), CHU Pontchaillou [Rennes], Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Bordeaux [Bordeaux], Humanitas University [Milan] (Hunimed), P01 CA23766, U.S. Department of Health & Human Services | National Institutes of Health, U.S. Department of Health & Human Services | National Institutes of Health, 20575, Associazione Italiana per la Ricerca sul Cancro, Università degli Studi di Milano [Milano] (UNIMI), University of Bologna, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), 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), Merryman R.W., Castagna L., Giordano L., Ho V.T., Corradini P., Guidetti A., Casadei B., Bond D.A., Jaglowski S., Spinner M.A., Arai S., Lowsky R., Shah G.L., Perales M.-A., De Colella J.M.S., Blaise D., Herrera A.F., Shouse G., Spilleboudt C., Ansell S.M., Nieto Y., Badar T., Hamadani M., Feldman T.A., Dahncke L., Singh A.K., McGuirk J.P., Nishihori T., Chavez J., Serritella A.V., Kline J., Mohty M., Dulery R., Stamatoulas A., Houot R., Manson G., Moles-Moreau M.-P., Orvain C., Bouabdallah K., Modi D., Ramchandren R., Lekakis L., Beitinjaneh A., Frigault M.J., Chen Y.-B., Lynch R.C., Smith S.D., Rao U., Byrne M., Romancik J.T., Cohen J.B., Nathan S., Phillips T., Joyce R.M., Rahimian M., Bashey A., Ballard H.J., Svoboda J., Torri V., Sollini M., De Philippis C., Magagnoli M., Santoro A., Armand P., Zinzani P.L., and Carlo-Stella C.
Subjects: 0301 basic medicine, Oncology, Male, Cancer Research, allogenic stem cell transplantation, PD-1 blockade, Hodgkin lymhpoma, [SDV]Life Sciences [q-bio], Programmed Cell Death 1 Receptor, Salvage therapy, 0302 clinical medicine, Young adult, Immune Checkpoint Inhibitors, ComputingMilieux_MISCELLANEOUS, Hematopoietic Stem Cell Transplantation, Hematology, Middle Aged, Prognosis, Hodgkin Disease, 3. Good health, Survival Rate, surgical procedures, operative, 030220 oncology & carcinogenesis, Female, medicine.drug, Adult, medicine.medical_specialty, Allogeneic transplantation, Cyclophosphamide, Adolescent, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Young Adult, Internal medicine, medicine, Humans, Transplantation, Homologous, Survival rate, Aged, Retrospective Studies, Salvage Therapy, business.industry, Retrospective cohort study, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Blockade, Transplantation, 030104 developmental biology, Drug Resistance, Neoplasm, Neoplasm Recurrence, Local, business, Follow-Up Studies
Abstract: International audience; Anti-PD-1 monoclonal antibodies yield high response rates in patients with relapsed/refractory classic Hodgkin lymphoma (cHL), but most patients will eventually progress. Allogeneic hematopoietic cell transplantation (alloHCT) after PD-1 blockade may be associated with increased toxicity, raising challenging questions about the role, timing, and optimal method of transplantation in this setting. To address these questions, we assembled a retrospective cohort of 209 cHL patients who underwent alloHCT after PD-1 blockade. With a median follow-up among survivors of 24 months, the 2-year cumulative incidences (CIs) of non-relapse mortality and relapse were 14 and 18%, respectively; the 2-year graft-versus-host disease (GVHD) and relapse-free survival (GRFS), progression-free survival (PFS), and overall survival were 47%, 69%, and 82%, respectively. The 180-day CI of grade 3-4 acute GVHD was 15%, while the 2-year CI of chronic GVHD was 34%. In multivariable analyses, a longer interval from PD-1 to alloHCT was associated with less frequent severe acute GVHD, while additional treatment between PD-1 and alloHCT was associated with a higher risk of relapse. Notably, post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis was associated with significant improvements in PFS and GRFS. While awaiting prospective clinical trials, PTCy-based GVHD prophylaxis may be considered the optimal transplantation strategy for this patient population.
Published: 2021
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36. The protease-inhibitor SerpinB3 as a critical modulator of the stem-like subset in human cholangiocarcinoma

Author: Matteo Parri, Cédric Coulouarn, Stefania Recalcati, Giuliana Cavalloni, Matteo Fassan, Claudia Campani, Luca Di Tommaso, Guido Torzilli, Andrea Cappon, Alessandra Biasiolo, Fabio Marra, Jesper B. Andersen, Chiara Raggi, B. Piombanti, Matteo Ramazzotti, Giulia Lori, Patricia Munoz-Garrido, Pietro Invernizzi, Laurent Sulpice, Santina Quarta, M. Correnti, Patrizia Pontisso, Caterina Peraldo Neia, Mirella Pastore, Monika Lewinska, Douglas Vnp Oliveira, Correnti, M, Cappon, A, Pastore, M, Piombanti, B, Lori, G, Oliveira, D, Munoz-Garrido, P, Lewinska, M, Andersen, J, Coulouarn, C, Sulpice, L, Peraldo Neia, C, Cavalloni, G, Quarta, S, Biasiolo, A, Fassan, M, Ramazzotti, M, Parri, M, Recalcati, S, di Tommaso, L, Campani, C, Invernizzi, P, Torzilli, G, Marra, F, Pontisso, P, Raggi, C, Humanitas Clinical and Research Center [Rozzano, Milan, Italy], Università degli Studi di Milano = University of Milan (UNIMI), Università degli Studi di Padova = University of Padua (Unipd), Università degli Studi di Firenze = University of Florence (UniFI), University of Copenhagen = Københavns Universitet (UCPH), CHU Pontchaillou [Rennes], Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Cancer Genomics Laboratory, Fondazione 'Edo ed Elvo Tempia Valenta', Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Candiolo Cancer Institute [Candiolo, Italie], Università degli studi di Torino = University of Turin (UNITO), Humanitas University [Milan] (Hunimed), Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), San Gerardo Hospital [Monza, Italy] (SGH), and Funding for this work was partially provided by the Italian Foundation of Cancer Research award (MFGA17588, IG23117) to Dr Raggi and (IG17786) to Prof. Marra, and in part by the University of Padua (Project: CPDA110795) to Prof. Pontisso. Dr Coulouarn was supported by Inserm, University of Rennes 1, and ITMO Cancer AVIESAN dans le cadre du Plan cancer (Non-coding RNA in cancerology: fundamental to translational). Dr Andersen, Dr Coulouarn, Dr Sulpice, Prof. Recalcati, Prof. Invernizzi and Dr Raggi are members of the European Network for the Study of Cholangiocarcinoma (ENSCCA) and participate in the initiative COST Action EURO-CHOLANGIO-NET granted by the COST Association (CA18122). Prof. Invernizzi is a member of the European Reference Network on Hepatological Diseases (ERN RARE LIVER). This study was partly supported by Italian Ministry of Health grants (PE-2016-02363915 and GR-2018-12367794). The authors thank AMAF Monza ONLUS and AIRCS for the unrestricted research funding.
Subjects: Homeobox protein NANOG, cancer stem cells, cancer stem cell, Epithelial-Mesenchymal Transition, [SDV.CAN]Life Sciences [q-bio]/Cancer, Mice, SCID, Cholangiocarcinoma, Mice, SOX2, Cancer stem cell, Antigens, Neoplasm, Mice, Inbred NOD, Cell Line, Tumor, Animals, Humans, Protease Inhibitors, Progenitor cell, Serpins, Hepatology, biology, SerpinB3, CD44, Liver Neoplasms, Membrane Proteins, Transfection, invasion, ADAM Proteins, Bile Ducts, Intrahepatic, Bile Duct Neoplasms, KLF4, Cell culture, Cancer research, biology.protein, Neoplastic Stem Cells, cholangiocarcinoma, Peptide Hydrolases
Abstract: Background and aims: Cholangiocarcinoma (CCA) is a form of primary liver cancer with limited therapeutic options. Recently, cancer stem cells (CSCs) have been proposed as a driving force of tumour initiation and dissemination, thus representing a crucial therapeutic target. The protease inhibitor SerpinB3 (SB3) has been identified in several malignancies including hepatocellular carcinoma. SB3 has been involved in the early events of hepatocarcinogenesis and is highly expressed in hepatic progenitor cells and in a mouse model of liver progenitor cell activation. However, only limited information on the possible role of SB3 in CCA stem-like compartment is available. Methods: Enrichment of CCA stem-like subset was performed by sphere culture (SPH) in CCA cell lines (CCLP1, HUCCT1, MTCHC01 and SG231). Quantitative RT-PCR and Western blotting were used to detect SB3 in both SPH and parental monolayer (MON) cells. Acquired CSC-like features were analysed using an endogenous and a paracrine in vitro model, with transfection of SB3 gene or addition of recombinant SB3 to cell medium respectively. SB3 tumorigenic role was explored in an in vivo mouse model of CCA by subcutaneous injection of SB3-transfected MON (MONSB3+) cells in immune-deficient NOD-SCID/IL2Rgnull (NSG) mice. SB3 expression in human CCA sections was investigated by immunohistochemistry. Overall survival (OS) and time to recurrence (TTR) analyses were carried out from a transcriptome database of 104 CCA patients. Results: SB3, barely detected in parental MON cells, was overexpressed in the same CCA cells grown as 3D SPH. Notably, MONSB3+ showed significant overexpression of genes associated with stemness (CD24, CD44, CD133), pluripotency (c-MYC, NOTCH1, STAT3, YAP, NANOG, BMI1, KLF4, OCT4, SOX2), epithelial mesenchymal transition (β-catenin, SLUG) and extracellular matrix remodelling (MMP1, MMP7, MMP9, ADAM9, ADAM10, ADAM17, ITGB3). SB3-overexpressing cells showed superior spherogenic capacity and invasion ability compared to control. Importantly, MONSB3+ exhibited activation of MAP kinases (ERK1/2, p38, JNK) as well as phosphorylation of NFκB (p65) in addition to up-regulation of the proto-oncogene β-catenin. All these effects were reversed after transient silencing of SB3. According to the in vitro finding, MONSB3+ cells retained high tumorigenic potential in NSG mice. SB3 overexpression was observed in human CCA tissues and analysis of OS as well as TTR indicated a worse prognosis in SB3+ CCA patients. Conclusion: These findings indicate a SB3 role in mediating malignant phenotype of CCA and identify a new therapeutic target.
Published: 2021
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37. Differential expression and regulation of MS4A family members in myeloid cells in physiological and pathological conditions

Author: Fabio Grizzi, Alberto Mantovani, Domenico Supino, Fabio Pasqualini, Marie-Astrid Boutet, Andrea Gianatti, Marina Sironi, Maria José Oliveira, Barbara Bottazzi, Silvia Carnevale, Matteo Stravalaci, Sarah N. Mapelli, Irene Mattiola, C. Pitzalis, Rémi Porte, Rita Silva-Gomes, Federico Colombo, Massimo Locati, Humanitas University [Milan] (Hunimed), Universidade do Porto, Istituto Clinico Humanitas [Milan] (IRCCS Milan), Regenerative Medicine and Skeleton research lab (RMeS), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), Queen Mary University of London (QMUL), Berlin Institute of Health (BIH), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Mucosal and Developmental Immunology [Berlin, Germany], IRCCS San Raffaele Scientific Institute [Milan, Italie], Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), 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)-Centre National de la Recherche Scientifique (CNRS), Azienda Ospedaliera Ospedale Papa Giovanni XXIII [Bergamo, Italy], University of Milan, Federal University of Health Sciences of Porto Alegre = Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Universidade do Porto = University of Porto, Regenerative Medicine and Skeleton (RMeS), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Università degli Studi di Milano = University of Milan (UNIMI), and Jehan, Frederic
Subjects: rheumatoid arthritis, [SDV.MHEP.AHA] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Myeloid, Immunology, Population, Biology, Monocytes, 03 medical and health sciences, 0302 clinical medicine, monocytes/Mϕs, medicine, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Immunology and Allergy, Gene family, Humans, Family, education, 030304 developmental biology, Regulation of gene expression, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, 0303 health sciences, education.field_of_study, MS4A6A, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, MS4A3, COVID-19, Membrane Proteins, Cell Biology, Antigens, CD20, In vitro, 3. Good health, Cell biology, MS4A4A, medicine.anatomical_structure, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, MS4A2, 030217 neurology & neurosurgery, Function (biology)
Abstract: The MS4A gene family encodes 18 tetraspanin-like proteins, most of which with unknown function. MS4A1 (CD20), MS4A2 (FcεRIβ), MS4A3 (HTm4), and MS4A4A play important roles in immunity, whereas expression and function of other members of the family are unknown. The present investigation was designed to obtain an expression fingerprint of MS4A family members, using bioinformatics analysis of public databases, RT-PCR, and protein analysis when possible. MS4A3, MS4A4A, MS4A4E, MS4A6A, MS4A7, and MS4A14 were expressed by myeloid cells. MS4A6A and MS4A14 were expressed in circulating monocytes and decreased during monocyte-to-Mϕ differentiation in parallel with an increase in MS4A4A expression. Analysis of gene expression regulation revealed a strong induction of MS4A4A, MS4A6A, MS4A7, and MS4A4E by glucocorticoid hormones. Consistently with in vitro findings, MS4A4A and MS4A7 were expressed in tissue Mϕs from COVID-19 and rheumatoid arthritis patients. Interestingly, MS4A3, selectively expressed in myeloid precursors, was found to be a marker of immature circulating neutrophils, a cellular population associated to COVID-19 severe disease. The results reported here show that members of the MS4A family are differentially expressed and regulated during myelomonocytic differentiation, and call for assessment of their functional role and value as therapeutic targets.
Published: 2021
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38. Gut microbiome in chronic rheumatic and inflammatory bowel diseases: Similarities and differences

Author: Julian R. Marchesi, David Moulin, Fatouma Salem, Tunay Kökten, Laurent Peyrin-Biroulet, Nadège Kindt, Anthony Lopez, Jean-Yves Jouzeau, Patrick Netter, Silvio Danese, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Imperial College London, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Humanitas University [Milan] (Hunimed), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), IMPACT GEENAGE, ANR-15-IDEX-0004,LUE,Isite LUE(2015), Salem, F, Kindt, N, Marchesi, Jr, Netter, P, Lopez, A, Kokten, T, Danese, S, Jouzeau, Jy, Peyrin-Biroulee, L, and Moulin, D
Subjects: Male, Gut flora, Inflammatory bowel disease, 0302 clinical medicine, Medicine, Intestinal Mucosa, Child, Review Articles, Aged, 80 and over, biology, Microbiota, Gastroenterology, Inflammatory Bowel Diseases, Middle Aged, 3. Good health, Intestines, chronic rheumatic diseases, Oncology, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, medicine.symptom, Adult, Adolescent, Inflammation, digestive system, Young Adult, 03 medical and health sciences, Immune system, Immunity, Rheumatic Diseases, Humans, Aged, gut microbiota, business.industry, biology.organism_classification, medicine.disease, immunity, eye diseases, digestive system diseases, Chronic disorders, Gut microbiome, Gastrointestinal Microbiome, inflammation, Chronic Disease, Immunology, Dysbiosis, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; INTRODUCTION:Inflammatory bowel diseases (IBDs) and chronic rheumatic diseases (CRDs) are systemic chronic disorders sharing common genetic, immune and environmental factors. About half of patients with IBD develop rheumatic ailments and microscopic intestinal inflammation is present in up to half of CRD patients. IBD and CRD patients also share a common therapeutic armamentarium. Disequilibrium in the complex realm of microbes (known as dysbiosis) that closely interact with the gut mucosal immune system has been associated with both IBD and CRD (spondyloarthritis and rheumatoid arthritis). Whether dysbiosis represents an epiphenomenon or a prodromal feature remains to be determined.METHODS:In an attempt to further investigate whether specific gut dysbiosis may be the missing link between IBD and CRD in patients developing both diseases, we performed here a systematic literature review focusing on studies looking at bacterial microbiota in CRD and/or IBD patients.RESULTS:We included 80 studies, with a total of 3799 IBD patients without arthritis, 1084 CRD patients without IBD, 132 IBD patients with arthropathy manifestations and 12 spondyloarthritis patients with IBD history. Overall, this systematic review indicates that an increase in Bifidobacterium, Staphylococcus, Enterococcus, Lactobacillus, Pseudomonas, Klebsiella and Proteus genera, as well as a decrease in Faecalibacterium, Roseburia genera and species belonging to Verrucomicrobia and Fusobacteria phyla are common features in IBD and CRD patients, whereas dozens of bacterial species are specific features of CRD and IBD.CONCLUSION:Further work is needed to understand the functions of bacteria and of their metabolites but also to characterize fungi and viruses that are commonly found in these patients.© Author(s) 2019.
Published: 2019
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39. Clinical efficacy of sublingual immunotherapy tablets for allergic rhinitis is unlikely to be derived from in vitro allergen-release data

Author: Laurent Mascarell, Pascal Demoly, Ulrich Wahn, Efstrathios Karagiannis, Catherine Bos, Giovanni Passalacqua, Philippe Devillier, Giorgio Walter Canonica, Thomas B. Casale, Gestionnaire, Hal Sorbonne Université, Department of Internal Medicine [Milan, Italy], Humanitas University [Milan] (Hunimed)-Research Hospital ICH [Milan, Italy], Laboratoire de recherche sur les mécanismes moléculaires et pharmacologiques de l’obstruction bronchique (LOBIP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Foch [Suresnes], Department of Internal Medicine [Tampa, FL, USA] (Division of Allergy/Immunology ), University of South Florida [Tampa] (USF), Département pneumologie et addictologie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Sorbonne Université (SU), Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département de Médecine Interne [Antony, France], Stallergenes Greer (France, Antony), Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Università degli studi di Genova = University of Genoa (UniGe), Department of Paediatric Pneumology and Immunology [Berlin, Germany], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and University of Genoa (UNIGE)
Subjects: safety, 0301 basic medicine, efficacy, Immunology, dissolution, formulation, grass pollen, Pharmacology, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, Allergen, Grass pollen, Immunology and Allergy, Medicine, Potency, Sublingual immunotherapy, Clinical efficacy, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, dissolution, Administration, allergic rhinitis, efficacy, formulation, grass pollen, safety, sublingual immunotherapy tablet, 030203 arthritis & rheumatology, allergic rhinitis, business.industry, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Slit, In vitro, 3. Good health, Bioavailability, 030104 developmental biology, sublingual immunotherapy tablet, Administration, in vitro dissolution, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, business, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology
Abstract: International audience; Introduction: Allergen bioavailability underpins the efficacy and safety of SLIT tablets. Three product-related factors are likely to influence this: tablet potency, formulation and sublingual holding time.Areas covered: Tablet formulation determines the rate and extent of solubilized allergen release. Using validated in vitro dissolution assays, the two licensed grass pollen SLIT tablets are shown to release ≥85% of their total allergenic activity within several minutes. Sublingual holding time affects the contact duration between solubilized allergens and sublingual tissue. Maximal uptake of allergens by sublingual tissue requires ~5 minutes, with little uptake occurring within the first minute. A higher potency tablet with longer sublingual holding time would provide higher bioavailability, while faster rates of allergen release in vitro are unlikely to translate to a greater increase in bioavailability. Differences in dissolution times cannot serve as a surrogate of in vivo bioavailability, and are not related to differences in efficacy at the marketed tablet dosages. Rapid in vitro dissolution is likely not a key requirement for inducing a potent immune response.Expert opinion: In vitro dissolution cannot predict the clinical efficacy of SLIT tablets but could be important in immune tolerance and safety. In addition, a discontinuous administration regimen may have benefits for adherence and cost without compromising efficacy.
Published: 2019
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40. HLA-A29 Birdshot Retinochoroiditis in Its 5th Decade: Selected Glimpses into the Intellectual Meanderings and Progresses in the Knowledge of a Long-Time Misunderstood Disease

Author: Christine Fardeau, Philippe Kestelyn, Ioannis Papasavvas, Carlos Pavesio, Carl P. Herbort, Piergiorgio Neri, Marina Papadia, Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), Moorfields Eye Hospital, Service d'Ophtalmologie [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), Cleveland Clinic Abu Dhabi [Abou Dabi, Émirats arabes unis], Case Western Reserve University [Cleveland], Ghent University Hospital, and Montchoisi Clinic [Lausanne, Switzerland]
Subjects: 0301 basic medicine, medicine.medical_specialty, Medicine (General), Hla testing, Indocyanine green angiography, Clinical Biochemistry, HLA-A29 birdshot retinochoroiditis, Severe disease, Disease, Imaging modalities, 03 medical and health sciences, 0302 clinical medicine, R5-920, Immunopathology, fluorescein angiography, medicine, clinicopathology, immunopathology, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, optical coherence tomography, medicine.diagnostic_test, business.industry, Fluorescein angiography, 3. Good health, 030104 developmental biology, Perspective, diagnostic criteria, 030221 ophthalmology & optometry, Radiology, business, indocyanine green angiography
Abstract: International audience; The appraisal of HLA-A29 birdshot retinochoroiditis (BRC) was fraught with pitfalls and misunderstandings. Progress in investigational methods has led to better knowledge and management of the disease. Our aim was to assess some of the steps that have led to better characterisation of the clinical entity of BRC. We performed a literature search analysing the relevant progress in disease origin, investigational and imaging methods, clinicopathology and classification, diagnostic criteria and management. Following developments were judged essential in the better appraisal and understanding of the disease: (1) new immunopathological hypotheses regarding the role of endoplasmic reticulum peptidases, (2) the essential importance of HLA testing, (3) relevant imaging modalities among which indocyanine green angiography is crucial, (4) diagnostic criteria that allow early diagnosis and (5) need of an early prolonged, as well as aggressive treatment combining more than one immunosuppressive agent. Based on these findings it is now possible to better define BRC, an indolent however severe disease, unlike thought before, involving the choroidal stroma and the retina independently and concomitantly that can be diagnosed early thanks to indocyanine green angiography and should be treated early and relentlessly.
Published: 2021
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41. Circulating and Synovial Pentraxin-3 (PTX3) Expression Levels Correlate With Rheumatoid Arthritis Severity and Tissue Infiltration Independently of Conventional Treatments Response

Author: Marie-Astrid Boutet, Alessandra Nerviani, Gloria Lliso-Ribera, Roberto Leone, Marina Sironi, Rebecca Hands, Felice Rivellese, Annalisa Del Prete, Katriona Goldmann, Myles J. Lewis, Alberto Mantovani, Barbara Bottazzi, Costantino Pitzalis, Regenerative Medicine and Skeleton research lab (RMeS), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Queen Mary University of London (QMUL), IRCCS Istituto Nazionale dei Tumori [Milano], Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), Regenerative Medicine and Skeleton (RMeS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), and Jehan, Frederic
Subjects: Male, rheumatoid arthritis, 0301 basic medicine, Pathology, inflammation, pathotypes, pentraxin-3, synovial tissue, Disease, Arthritis, Rheumatoid, 0302 clinical medicine, Synovial Fluid, Immunology and Allergy, Original Research, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, PTX3, Middle Aged, Synoviocytes, Serum Amyloid P-Component, Lymphatic Endothelium, C-Reactive Protein, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Antirheumatic Agents, Rheumatoid arthritis, Immunohistochemistry, Female, medicine.symptom, Adult, [SDV.MHEP.AHA] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], medicine.medical_specialty, government.form_of_government, Immunology, Inflammation, 03 medical and health sciences, medicine, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Aged, Autoantibodies, 030203 arthritis & rheumatology, business.industry, Autoantibody, RC581-607, medicine.disease, 030104 developmental biology, Synovial Cell, Case-Control Studies, government, Immunologic diseases. Allergy, business, Biomarkers
Abstract: AimsTo determine the relationship between PTX3 systemic and synovial levels and the clinical features of rheumatoid arthritis (RA) in a cohort of early, treatment naïve patients and to explore the relevance of PTX3 expression in predicting response to conventional-synthetic (cs) Disease-Modifying-Anti-Rheumatic-Drugs (DMARDs) treatment.MethodsPTX3 expression was analyzed in 119 baseline serum samples from early naïve RA patients, 95 paired samples obtained 6-months following the initiation of cs-DMARDs treatment and 43 healthy donors. RNA-sequencing analysis and immunohistochemistry for PTX3 were performed on a subpopulation of 79 and 58 synovial samples, respectively, to assess PTX3 gene and protein expression. Immunofluorescence staining was performed to characterize PTX3 expressing cells within the synovium.ResultsCirculating levels of PTX3 were significantly higher in early RA compared to healthy donors and correlated with disease activity at baseline and with the degree of structural damages at 12-months. Six-months after commencing cs-DMARDs, a high level of PTX3, proportional to the baseline value, was still detectable in the serum of patients, regardless of their response status. RNA-seq analysis confirmed that synovial transcript levels of PTX3 correlated with disease activity and the presence of mediators of inflammation, tissue remodeling and bone destruction at baseline. PTX3 expression in the synovium was strongly linked to the degree of immune cell infiltration, the presence of ectopic lymphoid structures and seropositivity for autoantibodies. Accordingly, PTX3 was found to be expressed by numerous synovial cell types such as plasma cells, fibroblasts, vascular and lymphatic endothelial cells, macrophages, and neutrophils. The percentage of PTX3-positive synovial cells, although significantly reduced at 6-months post-treatment as a result of global decreased cellularity, was similar in cs-DMARDs responders and non-responders.ConclusionThis study demonstrates that, early in the disease and prior to treatment modification, the level of circulating PTX3 is a reliable marker of RA activity and predicts a high degree of structural damages at 12-months. In the joint, PTX3 associates with immune cell infiltration and the presence of ectopic lymphoid structures. High synovial and peripheral blood levels of PTX3 are associated with chronic inflammation characteristic of RA. Additional studies to determine the mechanistic link are required.
Published: 2021
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42. Disease burden and economic impact of diagnosed non‐alcoholic steatohepatitis in five European countries in 2018: A cost‐of‐illness analysis

Author: Lawrence Serfaty, Emmanuel Tsochatzis, Laurent Castera, Jorge Mestre-Ferrandiz, S. Cure, Victoria Higgins, Rachel Elliott, Manuel Romero-Gómez, Javier Crespo, Stephen D Ryder, A. Morgan, Vlad Ratziu, Philip N. Newsome, Vincenzo Atella, S. Hartmanis, Salvador Augustin, Lefteris Floros, Vincent Leroy, Victor de Lédinghen, Jeffrey V. Lazarus, Jérôme Boursier, Jörn M. Schattenberg, S. Vasudevan, Heike Bantel, A. Trylesinski, Elisabetta Bugianesi, Lynne Pezzullo, Alessio Aghemo, Achim Kautz, University Medical Center [Mainz], Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), University of Birmingham [Birmingham], Hôpital de Hautepierre [Strasbourg], Humanitas University [Milan] (Hunimed), Vall d'Hebron University Hospital [Barcelona], Royal Free Hospital [London, UK], CHU Bordeaux [Bordeaux], Università degli studi di Torino (UNITO), Hospital Universitario Virgen del Rocío [Sevilla], Medizinische Hochschule Hannover (MHH), University of Nottingham, UK (UON), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Universitaire [Grenoble] (CHU), Marqués de Valdecilla University Hospital [Santander], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), PHMR Limited [London, UK], Università degli Studi di Roma Tor Vergata [Roma], Independent Economics Consultant [Madrid, Spain], University of Manchester [Manchester], Kautz5 [Köln, Germany], Deloitte [Canberra, Australia], Deloitte [Victoria, Australia], Intercept Pharmaceuticals [London, UK] (IP), Adelphi Real World [Cheshire, UK], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Università degli studi di Torino = University of Turin (UNITO), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and BOURGEAIS, Véronique
Subjects: economic impact, Adult, cost‐of‐illness analysis, non-alcoholic steatohepatitis (NASH), [SDV]Life Sciences [q-bio], Population, Psychological intervention, burden of disease, 03 medical and health sciences, 0302 clinical medicine, Cost of Illness, Non-alcoholic Fatty Liver Disease, Economic cost, healthcare resource utilisation, Germany, Health care, medicine, non‐alcoholic steatohepatitis (NASH), Humans, cost-of-illness analysis, Disease management (health), education, Socioeconomic status, Disease burden, ComputingMilieux_MISCELLANEOUS, education.field_of_study, Hepatology, business.industry, medicine.disease, digestive system diseases, United Kingdom, 3. Good health, [SDV] Life Sciences [q-bio], Europe, Italy, Spain, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Original Article, Liver Disease and Public Health, France, Steatohepatitis, business, Demography
Abstract: BACKGROUND AND AIMS: Non-alcoholic steatohepatitis (NASH) is a chronic disease that can progress to end-stage liver disease (ESLD). A large proportion of early-stage NASH patients remain undiagnosed compared to those with advanced fibrosis, who are more likely to receive disease management interventions. This study estimated the disease burden and economic impact of diagnosed NASH in the adult population of France, Germany, Italy, Spain and the United Kingdom (UK) in 2018.METHODS: The socioeconomic burden of diagnosed NASH was estimated using cost-of-illness methodology applying a prevalence approach to estimate the number of adults with NASH and the attributable economic and wellbeing costs. Given undiagnosed patients do not incur costs in the study, the probability of diagnosis is central to cost estimation. The analysis was based on literature review, databases and consultation with clinical experts, economists and patient groups.RESULTS: The proportion of adult NASH patients with a diagnosis ranged from 11.9% to 12.7% across countries, which increased to 38.8% to 39.1% for advanced fibrosis (F3 to F4 compensated cirrhosis). Total economic costs were €8,548-19,546M. Of these, health system costs were €619-1,292M. Total wellbeing costs were €41,536-90,379M. The majority of the undiagnosed population (87.3% to 88.2% of total prevalence) was found to have early stage NASH which, left untreated, may progress to more resource consuming ESLD over time.CONCLUSIONS: This study found the majority of economic and wellbeing costs of NASH are experienced in late disease stages. Earlier diagnosis and care of NASH patients could reduce future healthcare costs.
Published: 2021
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43. 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
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44. Integrative Analysis Reveals a Molecular Stratification of Systemic Autoimmune Diseases

Author: Isabel Almeida, Divi Cornec, Torsten Witte, Tania F. Rowley, Tianlu Li, Elena Carnero-Montoro, Mariana Brandão, Antonio Garcia-Gomez, Nancy Azevedo, Esmeralda Neves, Ana Lisa Taylor Tavares, Ana Campar, Jacques-Olivier Pers, Nicolas Hunzelmann, Ellen De Langhe, Ernst R. Dow, Magdolna Deák, Jorge Kageyama, Francisco Javier Garrancho, Gerard Espinosa, Carlo Chizzolini, Laleh Khodadadi, Falk Hiepe, Maria Angeles Aguirre-Zamorano, Marta E. Alarcón-Riquelme, Rosario Lopez-Pedrera, Anne Buttgereit, Ricard Cervera, Javier Rodríguez-Ubreva, Fernanda Genre, Jerome Wojcik, Begoña Ubilla Garcia, Héctor Navarro-Linares, Maria Orietta Borghi, N.T. Baerlecken, Katja Kniesch, Yolanda Jiménez Gómez, Zuzanna Makowska, Martin Kerick, Elena Trombetta, Pierre-Emmanuel Jouve, Lorenzo Beretta, Ricardo Blanco Alonso, Bénédicte Rouvière, Isabel Díaz Quintero, Michael Zauner, Ralf Lesche, Daniel Toro-Domínguez, Manuel Rodriguez Maresca, Attila Balog, Pier Luigi Meroni, Qingyu Cheng, Georg Stummvoll, Johan Frostegård, Javier Martín, Márta Bocskai, Joerg Mueller, Tommaso Schioppo, Chris Chamberlain, Sonja Dulic, László Kovács, Raquel López Mejías, Velia Gerl, Francesc Català-Moll, Robert J. Benschop, Sara Remuzgo, Carolina Artusi, María Teruel, Eduardo Collantes-Estevez, Miguel A. González-Gay, Silvia Thiel, Bernard Lauwerys, Maria Gerosa, Yves Renaudineau, Pedro Carmona-Sáez, Raquel Faria, Rocío Aguilar-Quesada, Sepideh Babaei, Nuria Barbarroja, Maria Hernandez-Fuentes, María Concepción Fernández Roldán, Sambasiva P. Rao, Aurélie De Groof, Montserrat Alvarez, Anne-Lise Maudoux, Sikander Hayat, Guillermo Barturen, Maria Juarez, Damiana Álvarez-Errico, Alfonso Corrales Martínez, Julie Ducreux, Lucas Le Lann, Norberto Ortego, Jacqueline Marovac, Sandrine Jousse-Joulin, Enrique Raya, Laurence Laigle, Concepción Marañón, Esteban Ballestar, Manuel Martínez-Bueno, Barbara Vigone, Rik Lories, Doreen Belz, Gabriella Kádár, Gaia Montanelli, Fátima Farinha, Divya Thiagaran, M.C. Castro-Villegas, Christophe Jamin, Alain Saraux, Carlos Vasconcelos, Emanuele de Rinaldis, Donatienne Wynar, Enrique de Ramón, Antonio López-Berrio, Tania Anjos, Alejandro Escudero-Contreras, Ian White, Valérie Devauchelle-Pensec, Ignasi Rodríguez-Pintó, Nieves Varela, Quentin Simon, Michaela Lehner, Inmaculada Jiménez Moleón, Aleksandra Maria Dufour, Rafaela Ortega-Castro, Marialbert Acosta-Herrera, Mcdonald Fiona Mcdougall, Yiannis Ioannou, Jonathan Cremer, António Marinho, Jordi Martorell-Marugán, Centre for Genomics and Oncological Research (GENYO) Pfizer, University of Granada, Pharmaceuticals Division Bayer Pharma Aktiengesellschaft, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), University of Barcelona, Centro de Genomica e Investigacion Oncologica (GENYO), Department of Bioinformatics, Center for Genomics and Oncological Research (GENYO), Granada, Spain, Institute of Parasitology and Biomedicine (IPB - GRANADA), Spanish National Research Council (CSIC), LabEX IGO Immunothérapie Grand Ouest, Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), UCB Pharma, Slough SL1 3WE, United Kingdom, Centre for Genomics and Oncological Reearch (GENYO), Andalusian Public Health System Biobank, Granada, Spain, Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Universidade do Porto, Servico de Immunologica EX-CICAP, Servico de Imunologica EX-CICAP, Unidade de Imunologia Clínica, Centro Hospitalar do Porto, Portugal, Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), Scleroderma Unit, Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], Bellvitge Biomedical Research Institute IDIBELL [Barcelona, Spain], Karolinska Institutet [Stockholm], Universidad de Cantabria [Santander], Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Klinikum Leverkusen Teaching Hospital of the University of Cologne, Hannover Medical School [Hannover] (MHH), Medical University of Vienna, Vienna, Austria, Medical University of Vienna, General Hospital of Vienna, Hospital Reina Sofía, Hospital Regional Universitario de Málaga [Spain], Hospital Universitario San Cecilio, Hospital Universitario Virgen de las Nieves, Università degli Studi di Milano [Milano] (UNIMI), Université Catholique de Louvain = Catholic University of Louvain (UCL), AltraBio [Lyon], Geneva University Hospital (HUG), University of Szeged [Szeged], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Sanofi [Cambridge, MA, USA], Sanofi Genzyme, Eli Lilly, Indianapolis, USA, UCB Celltech [Slough, UK], Institut de Recherches Internationales Servier [Suresnes] (IRIS), Quartzbio, Geneva, Instituto de Parasitología y Biomedicina 'López-Neyra', Fondazione IRCCS Ca’ Granda – Ospedale Maggiore Policlinico [Milan, Italy], Bellvitge Institute for Biomedical Research, Bayer HealthCare, Berlin, Centre for Genomics and Oncological Research Pfizer [Granada, Spain], University of Granada [Granada]-Andalusian Regional Government [Granada, Spain], Michel, Geneviève, Universidad de Granada = University of Granada (UGR), Nantes Université (Nantes Univ), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Universidade do Porto = University of Porto, University of Cologne, Hospital Regional Universitario de Málaga = Regional University Hospital of Malaga [Spain], Università degli Studi di Milano = University of Milan (UNIMI), Universidad de Granada = University of Granada (UGR)-Andalusian Regional Government [Granada, Spain], UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, and UCL - (SLuc) Service de rhumatologie
Subjects: 0301 basic medicine, Adult, Epigenomics, Male, [SDV.IMM] Life Sciences [q-bio]/Immunology, Cross-sectional study, Immunology, Arthritis, Bioinformatics, Scleroderma, Autoimmune Diseases, Transcriptome, Arthritis, Rheumatoid, 03 medical and health sciences, Epigenome, 0302 clinical medicine, Rheumatology, medicine, Immunology and Allergy, Cluster Analysis, Humans, Lupus Erythematosus, Systemic, Undifferentiated Connective Tissue Diseases, Aged, Mixed Connective Tissue Disease, 030203 arthritis & rheumatology, Inflammation, Science & Technology, Lupus erythematosus, Scleroderma, Systemic, business.industry, Gene Expression Profiling, Case-control study, Middle Aged, medicine.disease, Antiphospholipid Syndrome, 3. Good health, Clinical trial, Gene expression profiling, 030104 developmental biology, Cross-Sectional Studies, Sjogren's Syndrome, Case-Control Studies, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Interferons, business, Life Sciences & Biomedicine
Abstract: OBJECTIVE: Clinical heterogeneity, a hallmark of systemic autoimmune diseases, impedes early diagnosis and effective treatment, issues that may be addressed if patients could be classified into groups defined by molecular pattern. This study was undertaken to identify molecular clusters for reclassifying systemic autoimmune diseases independently of clinical diagnosis. METHODS: Unsupervised clustering of integrated whole blood transcriptome and methylome cross-sectional data on 955 patients with 7 systemic autoimmune diseases and 267 healthy controls was undertaken. In addition, an inception cohort was prospectively followed up for 6 or 14 months to validate the results and analyze whether or not cluster assignment changed over time. RESULTS: Four clusters were identified and validated. Three were pathologic, representing "inflammatory," "lymphoid," and "interferon" patterns. Each included all diagnoses and was defined by genetic, clinical, serologic, and cellular features. A fourth cluster with no specific molecular pattern was associated with low disease activity and included healthy controls. A longitudinal and independent inception cohort showed a relapse-remission pattern, where patients remained in their pathologic cluster, moving only to the healthy one, thus showing that the molecular clusters remained stable over time and that single pathogenic molecular signatures characterized each individual patient. CONCLUSION: Patients with systemic autoimmune diseases can be jointly stratified into 3 stable disease clusters with specific molecular patterns differentiating different molecular disease mechanisms. These results have important implications for future clinical trials and the study of nonresponse to therapy, marking a paradigm shift in our view of systemic autoimmune diseases. ispartof: ARTHRITIS & RHEUMATOLOGY vol:73 issue:6 pages:1073-1085 ispartof: location:United States status: published
Published: 2021
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45. NASH limits anti-tumour surveillance in immunotherapy-treated HCC

Author: Stephan Spahn, Florian Müller, Revant Gupta, Dominik Pfister, Kornelius Schulze, Pierre Bedossa, Eleni Kotsiliti, Lars Zender, Mathias Heikenwalder, Nicolás Gonzalo Núñez, Peter Schirmacher, Axel Schulz, Jan Kosla, Adrian T. Billeter, Thomas Engleitner, Aleksandra Deczkowska, Danijela Heide, Donato Inverso, Susanne Roth, Olivier Govaere, Carla Montironi, Martha M. Kirstein, Dan G. Duda, Antonio D'Alessio, Jörn M. Schattenberg, Ekaterina Friebel, Tiziana Pressiani, F. Hucke, Jörg Trojan, Michael Bitzer, Suhail Yousuf, Bernhard Scheiner, Marina Ruiz de Galarreta, Markus Peck-Radosavljevic, Michael Allison, Nuh N. Rahbari, Simon Cockell, Brinda Emu, Ahmed Kaseb, David J. Pinato, Matthias P. Ebert, Joachim C. Mertens, Jean-François Dufour, Fabian Rössler, Achim Weber, Katharina Wolter, Thomas Decaens, Amaia Lujambio, Anja Moncsek, Daniela Lenggenhager, Katharina Pomej, Nisar P. Malek, Fabian Finkelmeier, Elisabetta Bugianesi, Valentina Leone, Ann K. Daly, Michael Dudek, Manfred Claassen, Zuzana Macek Jilkova, Henning Wege, Florian Castet, Marta Szydlowska, Beat P. Müller-Stich, Ramy Younes, Nicola Personeni, Philipp K. Haber, Marco Bueter, Manfred Jugold, Andrea Schietinger, Hiroto Kikuchi, Ido Amit, Sandra Koch, Dina Tiniakos, Ana Teijeiro, Jan-Philipp Mallm, Josep M. Llovet, Indrabahadur Singh, Percy A. Knolle, Sara De Dosso, Roland Rad, Arndt Vogel, Henrik E. Mei, Burkhard Becher, Nabil Djouder, Tom Luedde, Felix Meissner, Oliver Waidmann, Parice N. Marche, Viktor Umansky, Hellmut G. Augustin, Thomas U. Marron, Matthias Pinter, Mengjie Qiu, Arndt Weinmann, Ankit Sinha, Kristian Unger, Assaf Weiner, Vlad Ratziu, Quentin M. Anstee, Kristin Stirm, Yi Hsiang Huang, Alexander Siebenhüner, Fabian Kütting, Lorenza Rimassa, Dirk Waldschmidt, Masatoshi Kudo, Marc Ringelhan, Michele Vacca, Roser Pinyol, Fabio Marra, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Novo Nordisk A/S [Maløv, Denmark], Universität Zürich [Zürich] = University of Zurich (UZH), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Newcastle University [Newcastle], Medizinische Universität Wien = Medical University of Vienna, University of Tübingen, UniversitätsKlinikum Heidelberg, Weizmann Institute of Science [Rehovot, Israël], Max Planck Institute of Biochemistry (MPIB), Max-Planck-Gesellschaft, Technical University of Munich (TUM), University hospital of Zurich [Zurich], Helmholtz-Zentrum München (HZM), Heidelberg University, Spanish National Cancer Research Center (CNIO), Icahn School of Medicine at Mount Sinai [New York] (MSSM), National and Kapodistrian University of Athens (NKUA), University of Turin, Addenbrooke's Hospital, Cambridge University NHS Trust, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), University Medical Center [Mainz], Cambridge University Hospitals - NHS (CUH), University of Cambridge [UK] (CAM), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7), Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), Hannover Medical School [Hannover] (MHH), University Medical Center of Schleswig–Holstein = Universitätsklinikum Schleswig-Holstein (UKSH), Kiel University, Klinikum Klagenfurt am Wörthersee, Universitätsklinikum Frankfurt, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Oncology Institute of Southern Switzerland (IOSI), Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Memorial Sloane Kettering Cancer Center [New York], Weill Medical College of Cornell University [New York], Heidelberg University Hospital [Heidelberg], Medical Faculty [Mannheim], Massachusetts General Hospital [Boston], University of Cologne, Deutsches Rheuma-ForschungsZentrum (DRFZ), Deutsches Rheuma-ForschungsZentrum, German Center for Infection Research, Partnersite Munich (DZIF), University Medical Center [Tubingen, Germany], Inselspital Bern, University of Bern, The University of Texas M.D. Anderson Cancer Center [Houston], Kindai University, National Yang Ming University (NYMU), Taipei Veterans General Hospital [Taiwan], Universitätsklinikum Tübingen - University Hospital of Tübingen, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Eberhard Karls University [Tübingen, Germany], Université Grenoble Alpes (UGA), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), CHU Grenoble, Hammersmith Hospital NHS Imperial College Healthcare, Università degli Studi del Piemonte Orientale - Amedeo Avogadro (UPO), Institució Catalana de Recerca i Estudis Avançats (ICREA), Pfister, Dominik [0000-0002-0542-2638], Núñez, Nicolás Gonzalo [0000-0003-3837-270X], Govaere, Olivier [0000-0002-4426-6930], Szydlowska, Marta [0000-0002-4660-899X], Gupta, Revant [0000-0002-0881-5074], Deczkowska, Aleksandra [0000-0003-0844-4346], Friebel, Ekaterina [0000-0003-1419-2376], Lenggenhager, Daniela [0000-0002-5382-9854], Moncsek, Anja [0000-0002-1191-5842], Inverso, Donato [0000-0003-0987-3345], Vacca, Michele [0000-0002-1973-224X], Marra, Fabio [0000-0001-8629-0878], Allison, Michael [0000-0003-3677-3294], D'Alessio, Antonio [0000-0002-9164-3671], Personeni, Nicola [0000-0002-7995-272X], Rimassa, Lorenza [0000-0001-9957-3615], Pomej, Katharina [0000-0002-2807-3565], Peck-Radosavljevic, Markus [0000-0002-0597-2728], Mallm, Jan-Philipp [0000-0002-7059-4030], Schietinger, Andrea [0000-0003-3644-1687], Augustin, Hellmut G [0000-0002-7173-4242], Kikuchi, Hiroto [0000-0002-3601-8435], Duda, Dan G [0000-0001-7065-8797], Mei, Henrik E [0000-0003-0697-7755], Schulz, Axel Ronald [0000-0002-5106-0148], Ringelhan, Marc [0000-0003-3131-5657], Lujambio, Amaia [0000-0002-2798-1481], Dufour, Jean-Francois [0000-0002-8062-1346], Kudo, Masatoshi [0000-0002-4102-3474], Djouder, Nabil [0000-0001-8423-1030], Zender, Lars [0000-0001-7626-2849], Pinato, David J [0000-0002-3529-0103], Rad, Roland [0000-0002-6849-9659], Mertens, Joachim C [0000-0003-2007-0308], Weber, Achim [0000-0003-0073-3637], Meissner, Felix [0000-0003-1000-7989], Amit, Ido [0000-0003-2968-877X], Knolle, Percy [0000-0003-2983-0414], Becher, Burkhard [0000-0002-1541-7867], Llovet, Josep M [0000-0003-0547-2667], Heikenwalder, Mathias [0000-0002-3135-2274], Apollo - University of Cambridge Repository, Max-Planck-Institut für Biochemie = Max Planck Institute of Biochemistry (MPIB), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Helmholtz Zentrum München = German Research Center for Environmental Health, Università degli studi di Torino = University of Turin (UNITO), Università degli Studi di Firenze = University of Florence (UniFI), MARCHE, Patrice, D’Alessio, Antonio [0000-0002-9164-3671], Augustin, Hellmut G. [0000-0002-7173-4242], Duda, Dan G. [0000-0001-7065-8797], Mei, Henrik E. [0000-0003-0697-7755], Pinato, David J. [0000-0002-3529-0103], Mertens, Joachim C. [0000-0003-2007-0308], and Llovet, Josep M. [0000-0003-0547-2667]
Subjects: Male, Carcinogenesis, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Programmed Cell Death 1 Receptor, CD8-Positive T-Lymphocytes, B7-H1 Antigen, 13/2, 13/1, Mice, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, LIVER-CANCER, R PACKAGE, RNA-SEQ, 14/19, Cancer, 0303 health sciences, Multidisciplinary, NONALCOHOLIC STEATOHEPATITIS, Liver Neoplasms, article, ddc, 3. Good health, 13/31, Multidisciplinary Sciences, medicine.anatomical_structure, Liver, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Disease Progression, Science & Technology - Other Topics, [SDV.IMM]Life Sciences [q-bio]/Immunology, 64/60, Tumor necrosis factor alpha, Immunotherapy, Adjuvant, 631/67, Carcinoma, Hepatocellular, [SDV.IMM] Life Sciences [q-bio]/Immunology, T cell, 610 Medicine & health, [SDV.CAN]Life Sciences [q-bio]/Cancer, 14/32, 03 medical and health sciences, 14/34, 13/21, [SDV.CAN] Life Sciences [q-bio]/Cancer, ADVANCED HEPATOCELLULAR-CARCINOMA, NAFLD, medicine, Animals, Humans, 14/35, 030304 developmental biology, Science & Technology, Tumor Necrosis Factor-alpha, business.industry, 631/250/251, medicine.disease, PHASE-III, digestive system diseases, 13/51, 14/63, 59/57, T-CELLS, Cancer research, Steatohepatitis, business, CD8
Abstract: Hepatocellular carcinoma (HCC) can have viral or non-viral causes1–5. Non-alcoholic steatohepatitis (NASH) is an important driver of HCC. Immunotherapy has been approved for treating HCC, but biomarker-based stratification of patients for optimal response to therapy is an unmet need6,7. Here we report the progressive accumulation of exhausted, unconventionally activated CD8+PD1+ T cells in NASH-affected livers. In preclinical models of NASH-induced HCC, therapeutic immunotherapy targeted at programmed death-1 (PD1) expanded activated CD8+PD1+ T cells within tumours but did not lead to tumour regression, which indicates that tumour immune surveillance was impaired. When given prophylactically, anti-PD1 treatment led to an increase in the incidence of NASH–HCC and in the number and size of tumour nodules, which correlated with increased hepatic CD8+PD1+CXCR6+, TOX+, and TNF+ T cells. The increase in HCC triggered by anti-PD1 treatment was prevented by depletion of CD8+ T cells or TNF neutralization, suggesting that CD8+ T cells help to induce NASH–HCC, rather than invigorating or executing immune surveillance. We found similar phenotypic and functional profiles in hepatic CD8+PD1+ T cells from humans with NAFLD or NASH. A meta-analysis of three randomized phase III clinical trials that tested inhibitors of PDL1 (programmed death-ligand 1) or PD1 in more than 1,600 patients with advanced HCC revealed that immune therapy did not improve survival in patients with non-viral HCC. In two additional cohorts, patients with NASH-driven HCC who received anti-PD1 or anti-PDL1 treatment showed reduced overall survival compared to patients with other aetiologies. Collectively, these data show that non-viral HCC, and particularly NASH–HCC, might be less responsive to immunotherapy, probably owing to NASH-related aberrant T cell activation causing tissue damage that leads to impaired immune surveillance. Our data provide a rationale for stratification of patients with HCC according to underlying aetiology in studies of immunotherapy as a primary or adjuvant treatment., In hepatocellular carcinoma driven by non-alcoholic steatohepatitis, aberrant T cell activation and impaired immune surveillance seem to make hepatocellular carcinoma less responsive to anti-PD1 or anti-PDL1 immunotherapy.
Published: 2021
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46. Personalized medicine for allergy treatment: Allergen immunotherapy still a unique and unmatched model

Author: Paolo Maria Matricardi, Ludger Klimek, Thomas B. Casale, Oliver Pfaar, Miguel Tortajada-Girbés, Ignacio J. Ansotegui, Cristoforo Incorvaia, Pascal Demoly, Marek Jutel, Petra Zieglmayer, Maximiliano Gómez, Philippe Devillier, Philippe Gevaert, Jean Bousquet, Petr Panzner, Giorgio Walter Canonica, Mona Al-Ahmad, Ralph Mösges, Stefania Arasi, Alain Didier, Piotr Kuna, Carmen Vidal, Peter Schmid-Grendelmeier, Carla Irani, Oxana Kurbacheva, Moises A. Calderon, Frédéric de Blay, Ulrich Wahn, Enrico Heffler, Alessandro Fiocchi, Adam T. Fox, Hae-Sim Park, Ruby Pawankar, Davide Caimmi, Claus Bachert, Natalija Novak, Margitta Worm, Nikolaos G. Papadopoulos, Silvia Scurati, Andrzej Bozek, Mário Morais-Almeida, Giovanni Passalacqua, Catherine Bos, Yoshitaka Okamoto, Natalia Ilina, Efstrathios Karagiannis, Robin O'Hehir, J. Christian Virchow, Adnan Custovic, ASST Pini-CTO, Kuwait University, Al-Rashed Allergy Center [Kuwait City], Hospital Quirónsalud Bizkaia [Bilbao], Bambino Gesù Children’s Hospital [Rome, Italy], Ghent University Hospital, Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], Stallergenes Greer (France, Antony), 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), Silesian Medical University, Katowice, Poland, Département pneumologie et addictologie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, University of South Florida [Tampa] (USF), University of Manchester [Manchester], University Hospital of South Manchester, CHU Strasbourg, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université de Montpellier (UM), Hôpital Foch [Suresnes], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Guy's and St Thomas' Hospital [London], Hospital San Bernardo, Humanitas Clinical and Research Center [Rozzano, Milan, Italy], Humanitas University [Milan] (Hunimed), Federal Institute of Immunology of Russia [Moscou], Hôtel-Dieu de France (HDF), Université Saint-Joseph de Beyrouth (USJ), Wrocław Medical University, Center for Rhinology and Allergology Wiesbaden, University Hospital Mannheim, Barlicki University Hospital, Medical University of Łódź (MUL), Monash University [Melbourne], Federal Medical-Biological Agency of Russia, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Hospital CUF Descobertas, University of Cologne, University Hospital Bonn, Chiba University Hospital, Charles University [Prague] (CU), Royal Manchester Children's Hospital, General Children's Hospital of Athens P & A Kyriakou, Ajou University School of Medicine, Ospedale Policlinico San Martino [Genoa], Università degli studi di Genova = University of Genoa (UniGe), Nippon Medical School [Tokyo, Japan], Philipps Universität Marburg = Philipps University of Marburg, University hospital of Zurich [Zurich], Dr Peset University Hospital, Universitat de València (UV), Complejo Hospitalario Universitario de Santiago de Compostela [Saint-Jacques-de-Compostelle, Espagne] (CHUS), University of Rostock, Herrada, Anthony, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-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 National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Toulouse [Toulouse], Wroclaw Medical University [Wrocław, Pologne], University of Genoa (UNIGE), and Philipps Universität Marburg
Subjects: Allergen immunotherapy, Endotype, MESH: Allergens, MESH: Hypersensitivity, Immunology, Disease, Bioinformatics, MESH: Precision Medicine, 03 medical and health sciences, 0302 clinical medicine, molecular diagnosis, Hypersensitivity, Immunology and Allergy, Medicine, Humans, Precision Medicine, MESH: Desensitization, Immunologic, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, MESH: Humans, business.industry, Mechanism (biology), MESH: Genomics, Genomics, personalized medicine, Allergens, treatable traits, Molecular diagnostics, Omics, 3. Good health, Biomarker (cell), omics, allergen immunotherapy, 030228 respiratory system, Desensitization, Immunologic, Personalized medicine, business, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology, 030215 immunology
Abstract: International audience; The introduction of personalized medicine (PM) has been a milestone in the history of medical therapy, because it has revolutionized the previous approach of treating the disease with that of treating the patient. It is known today that diseases can occur in different genetic variants, making specific treatments of proven efficacy necessary for a given endotype. Allergic diseases are particularly suitable for PM, because they meet the therapeutic success requirements, including a known molecular mechanism of the disease, a diagnostic tool for such disease, and a treatment blocking the mechanism. The stakes of PM in allergic patients are molecular diagnostics, to detect specific IgE to single-allergen molecules and to distinguish the causative molecules from those merely cross-reactive, pursuit of patient's treatable traits addressing genetic, phenotypic, and psychosocial features, and omics, such as proteomics, epi-genomics, metabolomics, and breathomics, to forecast patient's responsiveness to therapies, to detect biomarker and mediators, and to verify the disease control. This new approach has already improved the precision of allergy diagnosis and is likely to significantly increase, through the higher performance achieved with the personalized treatment, the effectiveness of allergen immunotherapy by enhancing its already known and unique characteristics of treatment that acts on the causes.
Published: 2021
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47. SARS-CoV-2 vaccination in IBD: more pros than cons

Author: Silvio Danese, Ferdinando D'Amico, Laurent Peyrin-Biroulet, Christian Rabaud, Humanitas University [Milan] (Hunimed), Humanitas Clinical and Research Center [Rozzano, Milan, Italy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université de Lorraine (UL), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), and Arnone, Djésia
Subjects: 0301 basic medicine, 2019-20 coronavirus outbreak, COVID-19 Vaccines, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV]Life Sciences [q-bio], MEDLINE, 03 medical and health sciences, 0302 clinical medicine, Humans, Medicine, Hepatology, business.industry, SARS-CoV-2, Comment, fungi, Gastroenterology, COVID-19, Inflammatory Bowel Diseases, 3. Good health, [SDV] Life Sciences [q-bio], Vaccination, Crohn's disease, 030104 developmental biology, Ulcerative colitis, Immunology, 030211 gastroenterology & hepatology, business, Immunosuppressive Agents
Abstract: International audience; Data on the efficacy and safety of SARS-CoV-2 vaccines are now available, but evidence for these vaccines in those who are immunocompromised (including patients with inflammatory bowel diseases) are lacking. As vaccination begins, questions on advantages and disadvantages can be partially addressed using the experience from other vaccines or immune-mediated inflammatory disorders.
Published: 2021
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48. Risk of relapse after anti-PD1 discontinuation in patients with Hodgkin lymphoma

Author: Marie Maerevoet, Jm Schiano, Bénédicte Deau, Mg Silva, Apasia Stamatoullas, Roch Houot, Guillaume Manson, Pauline Brice, Laurent Dercle, Herve Ghesquieres, Carmelo Carlo-Stella, Juliette Bouteloup, Kamal Bouabdallah, Charles Herbaux, Florence Poizeau, E. Nicolas-Virelizier, M. de Charette, Chloe Antier, CHU Pontchaillou [Rennes], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Instituto Português de Oncologia de Lisboa Francisco Gentil, CHU Bordeaux [Bordeaux], Hôpital Cochin [AP-HP], Centre Hospitalier Chalon-sur-Saône William Morey, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Léon Bérard [Lyon], Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Hospices Civils de Lyon (HCL), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre hospitalier universitaire de Nantes (CHU Nantes), Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Humanitas University [Milan] (Hunimed), Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Institut Gustave Roussy (IGR), Columbia University Medical Center (CUMC), Columbia University [New York], and Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)
Subjects: medicine.medical_specialty, Training set, business.industry, [SDV]Life Sciences [q-bio], Specific time, General Medicine, 3. Good health, 030218 nuclear medicine & medical imaging, Discontinuation, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, Refractory Hodgkin Lymphoma, Medicine, Hodgkin lymphoma, Radiology, Nuclear Medicine and imaging, In patient, Immunotherapy, Relapse risk, business, Anti pd1, Biomarkers, Checkpoint inhibitors
Abstract: International audience; Introduction - Patients with relapsed/refractory Hodgkin lymphoma (R/R HL) experience high response rates upon anti-PD1 therapy. In these patients, the optimal duration of treatment and the risk of relapse after anti-PD1 discontinuation are unknown. Methods - We retrospectively analyzed patients with R/R HL who responded to anti-PD1 monotherapy and discontinued the treatment either because of unacceptable toxicity or prolonged remission. A machine learning algorithm based on 17 candidate variables was trained and validated to predict progression-free survival (PFS) landmarked at the time of discontinuation of anti-PD1 therapy. Results - Forty patients from 14 centers were randomly assigned to training (n = 25) and validation (n = 15) sets. At the time of anti-PD1 discontinuation, patients had received treatment for a median duration of 11.2 (range, 0-time to best response was not statistically significant in discriminating patients with PFS lesser or greater than 12 months). Considering PFS status as a binary variable (alive or dead) at a specific time point (12 months) is convenient, intuitive and allows for comparing the value of potential predicting variables in these two groups of patients. Nonetheless, this approach has two drawbacks: first, it binarizes outcome; second, it excludes patients alive with a time to last follow up lesser 12 months. Therefore, it is less powerful to demonstrate statistically significant association with PFS even if it exists 5 months. Patients discontinued anti-PD1 treatment either because of prolonged remission (N = 27, 67.5%) or unacceptable toxicity (N = 13, 32.5%). Most patients were in CR (N = 35, 87.5%) at the time of anti-PD1 discontinuation. In the training set, the machine learning algorithm identified that the most important variables to predict PFS were patients' age, time to best response, and presence or absence of CR. The performance observed in the training set was validated in the validation set. Conclusion - In this pilot, proof of concept study using a machine learning algorithm, we identified biomarkers capable of predicting the risk of relapse after anti-PD1 discontinuation (age, time to best response, quality of response). Once confirmed, these simple biomarkers will represent useful tools to guide the management of these patients.
Published: 2021
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49. Gut mucosa alterations and loss of segmented filamentous bacteria in type 1 diabetes are associated with inflammation rather than hyperglycaemia

Author: Philippe J. Sansonetti, Matthieu Rouland, Maria Rescigno, Lucie Cagninacci, Nathalie Vergnolle, Sandra Guilmeau, Juliette Mouriès, Latif Rachdi, Lucie Beaudoin, Azadeh Saffarian, Agnès Lehuen, Dalale Gueddouri, Anne-Françoise Burnol, Ute Christine Rogner, Asmaa Tazi, Ophélie Rouxel, Léo Bertrand, Thierry Pedron, Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Pathogénie microbienne moléculaire, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Humanitas University [Milan] (Hunimed), Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), LabEx Inflamex, This work was supported by Agence Nationale de la Recherche (ANR-11-IDEX-0005-02 Laboratory of Excellence INFLAMEX and ANR-17-CE14-0002-01 Diab1MAIT), Fondation pour la Recherche Médicale (DEQ20140329520 and EQU201903007779), the INSERM crosscutting program on microbiota and the European Foundation for the Study of Diabetes–Juvenile Diabetes Research Foundation–MR, OR and LBer were supported by the French Ministry of Research., ANR-11-IDEX-0005,USPC,Université Sorbonne Paris Cité(2011), ANR-17-CE14-0002,Diab1MAIT,Rôle des cellules MAIT dans le diabète de type 1 chez l'homme et la souris(2017), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Fondation pour la Recherche Medicale (DEQ20140329520 and EQU201903007779), European Foundation for the Study of Diabetes-Juvenile Diabetes Research Foundation-MR, OR and LBer are supported by the French Ministry of Research, and the INSERM crosscutting program on microbiota is supported by the French Ministry of Research
Subjects: 0301 basic medicine, endocrine system diseases, medicine.medical_treatment, Segmented filamentous bacteria, intestinal microbiology, Inflammation, Gut flora, digestive system, Mice, 03 medical and health sciences, 0302 clinical medicine, Immune system, Diabetes Mellitus, medicine, Animals, Intestinal Mucosa, Autoimmune disease, Bacteria, biology, Insulin, digestive, oral, and skin physiology, Gastroenterology, Interleukin, Epithelial Cells, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, biology.organism_classification, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Gastrointestinal Microbiome, 3. Good health, Disease Models, Animal, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Diabetes Mellitus, Type 1, 030104 developmental biology, Hyperglycemia, 030220 oncology & carcinogenesis, Immunology, mucosal immunity, Cytokines, Dysbiosis, [SDV.IMM]Life Sciences [q-bio]/Immunology, medicine.symptom, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: ObjectiveType 1 diabetes (T1D) is an autoimmune disease caused by the destruction of pancreatic β-cells producing insulin. Both T1D patients and animal models exhibit gut microbiota and mucosa alterations, although the exact cause for these remains poorly understood. We investigated the production of key cytokines controlling gut integrity, the abundance of segmented filamentous bacteria (SFB) involved in the production of these cytokines, and the respective role of autoimmune inflammation and hyperglycaemia.DesignWe used several mouse models of autoimmune T1D as well as mice rendered hyperglycaemic without inflammation to study gut mucosa and microbiota dysbiosis. We analysed cytokine expression in immune cells, epithelial cell function, SFB abundance and microbiota composition by 16S sequencing. We assessed the role of anti-tumour necrosis factor α on gut mucosa inflammation and T1D onset.ResultsWe show in models of autoimmune T1D a conserved loss of interleukin (IL)-17A, IL-22 and IL-23A in gut mucosa. Intestinal epithelial cell function was altered and gut integrity was impaired. These defects were associated with dysbiosis including progressive loss of SFB. Transfer of diabetogenic T-cells recapitulated these gut alterations, whereas induction of hyperglycaemia with no inflammation failed to do so. Moreover, anti-inflammatory treatment restored gut mucosa and immune cell function and dampened diabetes incidence.ConclusionOur results demonstrate that gut mucosa alterations and dysbiosis in T1D are primarily linked to inflammation rather than hyperglycaemia. Anti-inflammatory treatment preserves gut homeostasis and protective commensal flora reducing T1D incidence.
Published: 2021
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50. Amyotrophic lateral sclerosis transcriptomics reveals immunological effects of low-dose interleukin-2

Author: Paul R. Heath, Cecilia Garlanda, Andrea Malaspina, P. Nigel Leigh, William Camu, Henrik Zetterberg, Christophe Masseguin, Gilbert Bensimon, Ilaria Giovannelli, Jean-Luc Veyrune, Abigail Brown, Ulf Andreasson, Dennis Wang, Nadhim Bayatti, Pamela J. Shaw, Massimo Locati, Ammar Al-Chalabi, Christine Payan, Safa Saker, Janine Kirby, Nicolas Pageot, John De Vos, Carey M. Suehs, Marius Mickunas, Raul Juntas-Morales, Timothy Tree, University of Sheffield [Sheffield], King‘s College London, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire de Biostatistique, Epidémiologie clinique, Santé Publique Innovation et Méthodologie [CHU Nîmes] (BESPIM), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Humanitas University [Milan] (Hunimed), Service de pharmacologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Istituto Clinico Humanitas [Milan] (IRCCS Milan), Barts & The London School of Medicine and Dentistry, University of Gothenburg (GU), Généthon, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Sahlgrenska University Hospital [Gothenburg], UCL, Institute of Neurology [London], and Brighton and Sussex Medical School (BSMS)
Subjects: Oncology, Interleukin 2, medicine.medical_specialty, amyotrophic lateral sclerosis, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Population, Disease, Placebo, Lower motor neuron, regulatory T cells, 03 medical and health sciences, transcriptomics, 0302 clinical medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Internal medicine, medicine, Amyotrophic lateral sclerosis, genes, education, Neuroinflammation, 030304 developmental biology, 0303 health sciences, education.field_of_study, business.industry, AcademicSubjects/SCI01870, General Engineering, clinical trial, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, medicine.disease, low-dose interleukin 2, 3. Good health, Clinical trial, medicine.anatomical_structure, interleukin-2, Original Article, AcademicSubjects/MED00310, regulatory t-lymphocytes, business, biological markers, 030217 neurology & neurosurgery, medicine.drug
Abstract: Amyotrophic lateral sclerosis is a fatal neurodegenerative disease causing upper and lower motor neuron loss and currently no effective disease-modifying treatment is available. A pathological feature of this disease is neuroinflammation, a mechanism which involves both CNS-resident and peripheral immune system cells. Regulatory T-cells are immune-suppressive agents known to be dramatically and progressively decreased in patients with amyotrophic lateral sclerosis. Low-dose interleukin-2 promotes regulatory T-cell expansion and was proposed as an immune-modulatory strategy for this disease. A randomized placebo-controlled pilot phase-II clinical trial called Immuno-Modulation in Amyotrophic Lateral Sclerosis was carried out to test safety and activity of low-dose interleukin-2 in 36 amyotrophic lateral sclerosis patients (NCT02059759). Participants were randomized to 1MIU, 2MIU-low-dose interleukin-2 or placebo and underwent one injection daily for 5 days every 28 days for three cycles. In this report, we describe the results of microarray gene expression profiling of trial participants' leukocyte population. We identified a dose-dependent increase in regulatory T-cell markers at the end of the treatment period. Longitudinal analysis revealed an alteration and inhibition of inflammatory pathways occurring promptly at the end of the first treatment cycle. These responses are less pronounced following the end of the third treatment cycle, although an activation of immune-regulatory pathways, involving regulatory T-cells and T helper 2 cells, was evident only after the last cycle. This indicates a cumulative effect of repeated low-dose interleukin-2 administration on regulatory T-cells. Our analysis suggested the existence of inter-individual variation amongst trial participants and we therefore classified patients into low, moderate and high-regulatory T-cell-responders. NanoString profiling revealed substantial baseline differences between participant immunological transcript expression profiles with the least responsive patients showing a more inflammatory-prone phenotype at the beginning of the trial. Finally, we identified two genes in which pre-treatment expression levels correlated with the magnitude of drug responsiveness. Therefore, we proposed a two-biomarker based regression model able to predict patient regulatory T-cell-response to low-dose interleukin-2. These findings and the application of this methodology could be particularly relevant for future precision medicine approaches to treat amyotrophic lateral sclerosis., Amyotrophic lateral sclerosis patients included in the IMODALS clinical trial (NCT02059759) were transcriptionally profiled to assess longitudinal blood expression changes. Low-dose-interleukin-2 was shown to promote dose and time-dependent Treg-marker upregulation. However, inter-individual variations were reported in the magnitude of Treg expansion and a two-biomarker model to predict target-engagement was proposed., Graphical Abstract Graphical Abstract
Published: 2021
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