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2. German Stroke Registry - Endovascular Treatment (GSR-ET)

Author

University Hospital of Cologne, Klinikum rechts der Isar, Technical University of Munich, RWTH Aachen University, University Hospital Tuebingen, Charite University, Berlin, Germany, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Sana Klinikum Offenbach, Goethe University, Klinikum Dortmund, KRH Klinikum Nordstadt, Asklepios Klinik Altona, Klinikum Altenburger Land, Klinikum Stadt Hanau, Klinikum Lüneburg, Ludwig-Maximilians - University of Munich, University of Göttingen, Krankenhaus Buchholz, Klinikum Osnabrück, Wuerzburg University Hospital, University of Giessen and Marburg, Sana Kliniken Lübeck, Mühlenkreiskliniken Minden, radprax MVZ Nordrhein, University Hospital Muenster, University Medical Center Rostock, Asklepios Klinik Wandsbek, Elbe Kliniken, Städtische Klinikum Braunschweig, Allgemeines Krankenhaus Celle, Bezirkskrankenhaus Günzburg, Klinikum Bremen-Mitte, gGmbH, University Medical Center Mainz, Klinikum Köln-Merheim, and University Hospital, Bonn

Published
2024

7. Study on the Effectiveness of Berlin Dissexuality Therapy as Part of the Model Project in Accordance With §65d SBG V (BEDIT-RCT)

Author

Hannover Medical School, Heinrich-Heine University, Duesseldorf, Klinikum Bamberg, Universitätsklinikum Kiel, University Medical Center Mainz, Uniklinikum Giessen und Marburg, University Hospital Ulm, Universitätsklinikum Leipzig, University Hospital Regensburg, Universitätsklinikum Hamburg-Eppendorf, and Klaus Michael Beier, Director, Institute for Sexual Research and Sexual Medicine

Published
2024

8. LITMUS Imaging Study

Author

Newcastle University, University of Nottingham, University of Cambridge, University of Seville, Pinnacle Clinical Research, PLLC, ICAN Nutrition Education and Research, Assistance Publique - Hôpitaux de Paris, University of Angers, University of Palermo, University of Turin, Italy, University Medical Center Mainz, University of Helsinki, University of Bern, Linkoeping University, Perspectum, Antaros Medical, Resoundant Inc, Pfizer, Novartis, Takeda, Boehringer Ingelheim, Intercept Pharmaceuticals, and Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Published
2024

9. Dual Guidance Structure for Evaluation of Patients With Unclear Diagnosis in Centers for Rare Diseases (ZSE-DUO)

Author

Hannover Medical School, University Hospital, Aachen, Allianz Chronischer Seltener Erkrankungen ACHSE e.V., Goethe University, Universität Münster, St. Josef Hospital Bochum, Otto-von-Guericke University Magdeburg, University Medical Center Mainz, University Hospital Regensburg, University Hospital Tuebingen, University Hospital Ulm, IKK gesund plus, Techniker Krankenkasse, University of Wuerzburg, Universitätsklinikum Hamburg-Eppendorf, AOK Hessen, and LWL-Universitätsklinikum der Ruhr-Universität Bochum

Published
2023

10. DZHK TORCH-Plus is a Registry for Patients With Cardiomyopathies and Serves as Source for Cardiovascular Research Studies (TORCH-Plus)

Author

University Medicine Greifswald, Charite University, Berlin, Germany, German Heart Center, University of Mannheim, University Hospital Schleswig-Holstein, Medical University of Hannover, Goethe University, Universitätsklinikum Hamburg-Eppendorf, University Medical Center Mainz, University Medical Center Goettingen, Deutsches Herzzentrum Muenchen, Technical University of Munich, University Hospital Munich, Kerckhoff Klinik, and Benjamin Meder, Deputy Director - Clinic of Cardiology, Angiology and Pneumology

Published
2023

12. ERANet-LAC CODE: International Care Of the Dying Evaluation

Author

Sue Ryder House administered by Pallmed, Mutualista Asociación Hospital Evangélico, Pallium Latinoamérica N.G.O, University Medical Center Mainz, University of Campinas, Brazil, and University of Liverpool

Published
2023

13. The European NAFLD Registry

Author

Newcastle-upon-Tyne Hospitals NHS Trust, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Institute of Cardiometabolism and Nutrition, France, University of Cambridge, Örebro University, Sweden, University of Bern, University of Oxford, University of Turin, Italy, University of Angers, University Hospital, Antwerp, Linkoeping University, University of Helsinki, UMC Utrecht, National and Kapodistrian University of Athens, University of Lisbon, University of Milan, University of Palermo, Catholic University of the Sacred Heart, Wuerzburg University Hospital, RWTH Aachen University, University of Nottingham, Medical University of Vienna, University of Birmingham, University of Florence, Assistance Publique - Hôpitaux de Paris, and University Medical Center Mainz

Published
2023

16. TRICuspid Intervention in Heart Failure Trial (TRICI-HF)

Author

Heart and Diabetes Center North Rhine-Westphalia, University Medical Center Mainz, Heart Center Leipzig - University Hospital, Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK), University of Leipzig, and Thomas Stocker, MD

Published
2022

17. Prediction of Outcomes After Surgery for Unruptured Intracranial Aneurysms (PRAEMIUM)

Author

Macquarie University, Australia, University of Melbourne, Kepler University Hospital, Medical University Innsbruck, General University Hospital, Prague, Universitätsklinikum Köln, Goethe University, University Medical Center Mainz, University of Göttingen, University Hospital Dresden, Charite University, Berlin, Germany, Heinrich-Heine University, Duesseldorf, University of Roma La Sapienza, University of Padova, University of Florence, Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta, University of Messina, Universita di Verona, Uniuversity of Genua, Italy, Leiden University Medical Center, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), UMC Utrecht, Burdenko Neurosurgery Institute, Sahlgrenska University Hospital, Sweden, University of Bern, Barrow Neurological Institute, Stanford University, Emory University, University of Wisconsin, Madison, University of California, San Francisco, University of Illinois at Chicago, Brigham and Women's Hospital, Mayo Clinic, University of California, Los Angeles, NorthShore University HealthSystem, and Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Published
2021

19. A Personalized Surveillance and Intervention Protocol for Patients With Familial Adenomatous Polyposis That Have Undergone (Procto)Colectomy

Author

Leiden University Medical Center, The Netherlands Cancer Institute, St Mark's Hospital Foundation, Hospital Clinic of Barcelona, Hôpital Edouard Herriot, Maria Sklodowska-Curie National Research Institute of Oncology, Hospital General Universitario de Alicante, University Medical Center Mainz, IRCCS Azienda Ospedaliero-Universitaria di Bologna, and Prof. Evelien Dekker, MD, PhD, Prof. dr. Evelien Dekker, MD, PhD

Published
2020

20. A Personalized Surveillance and Intervention Protocol for Duodenal and Gastric Polyposis in Patients With Familial Adenomatous Polyposis

Author

Leiden University Medical Center, The Netherlands Cancer Institute, St Mark's Hospital Foundation, Hospital Clinic of Barcelona, Hôpital Edouard Herriot, Maria Sklodowska-Curie National Research Institute of Oncology, Hospital General Universitario de Alicante, University Medical Center Mainz, IRCCS Azienda Ospedaliero-Universitaria di Bologna, and Prof. Evelien Dekker, MD, PhD, Prof. dr. Evelien Dekker, MD, PhD

Published
2020

23. Exercise for Depression (EXDEP)

Author

Department of Psychiatry and Psychotherapy, University Medical Center, Mainz and Prof. Dr. Dr. Perikles Simon, Professor for Sports Medicine MD PHD

Published
2018

25. Expanding the Spectrum of TEER Suitability: Evidence From the EXPAND G4 Post Approval Study

Author

Rogers, Jason, Asch, Federico, Sorajja, Paul, Mahoney, Paul, Price, Matthew, Maisano, Francesco, Denti, Paolo, Morse, Michael, Rinaldi, Michael, Bedogni, Francesco, de Marco, Federico, Rollefson, William, Chehab, Bassem, Williams, Mathew, Leurent, Guillaume, Morikawa, Takao, Asgar, Anita, Rodriguez, Evelio, von Bardeleben, Ralph Stephan, Kar, Saibal, University of California [Davis] (UC Davis), University of California (UC), Scripps Clinic [San Diego, CA, USA], CHU Pontchaillou [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), University Medical Center [Mainz], Los Robles Regional Medical Center [California], The EXPAND G4 study was funded and sponsored by Abbott. Dr Rogers has received institutional research funding from Abbott and Boston Scientific, and has received consulting fees from Abbott, Baylis, and Boston Scientific. Dr Asch’s work as director of an academic core laboratory is through institutional research grants (MedStar Health) with Abbott, Boston Scientific, Medtronic, Edwards Lifesciences, Neovasc, Ancora Heart, LivaNova, MVRx, InnovHeart, Polares Medical, and Aria CV. Dr Sorajja has received consulting fees from Abbott, Medtronic, Boston Scientific, vDyne, TriFlo, W.L. Gore & Associates, Anteris, Evolution Medical, Half Moon Medical, Neovasc, TeleFlex, and Shifamed, and has received grant support from Abbott, VDyne, Medtronic, and Highlife. Dr Mahoney serves as a consultant and proctor for Medtronic, Edwards Lifesciences, and Boston Scientific, is a consultant for Abbott, and has received research support from Edwards Lifesciences, Medtronic, Abbott, and Boston Scientific. Prof Maisano has received grant and/or institutional research support from Abbott, Medtronic, Edwards Lifesciences, Biotronik, Boston Scientific, NVT, and Terumo, has received consulting fees, honoraria (personal and institutional) from Abbott, Medtronic, Edwards Lifesciences, Xeltis, and Cardiovalve, has received royalty income and intellectual property rights from Edwards Lifesciences, and is a shareholder (including share options) in CardioGard, Magenta, SwissVortex, Transseptal Solutions, Occlufit, 4Tech, and Perifect. Dr Denti has received consulting and speaker fees from Abbott. Dr Morse is a consultant for Edwards Lifesciences. Dr Rinaldi has served on the advisory board for Boston Scientific, has taught courses for Abbott and Edwards Lifesciences, has served as a consultant for Abbott, Boston Scientific, and Edwards Lifesciences, has received research and grant support from Boston Scientific, and has served as a proctor for Abbott and Edwards Lifesciences. Dr Bedogni has received consulting and speaker fees from Abbott. Dr De Marco is a consultant and has provided paid expert testimony for Abbott and Boston Scientific. Dr Chehab has received study grants and consulting fees from Abbott, Edwards Lifesciences, and BioTronics. Dr Price has received consulting fees from ACIST, Medtronic, Biotronik, Boston Scientific, Abbott, Philips, InnovHeart, Shockwave, and W.L. Gore & Associates (outside the submitted work). Dr Williams has received research funding from Abbott, Medtronic, Boston Scientific, and Edwards Lifesciences. Dr Leurent has received proctoring, lecture, and consulting fees from Abbott. Dr Morikawa has received speaking, consulting, and proctoring fees from Abbott. Dr Asgar is a consultant for and has received research support from Abbott. Dr Rodriguez has received consulting fees from Abbott, AtriCure, Boston Scientific, Edwards Lifesciences, NeoChord, and Philips. Prof von Bardeleben has served in unpaid trial activities for Abbott, Edwards Lifesciences, Medtronic, and the University of Gottingen (IIT), and is an advisory board or Speakers Bureau member for Abbott Cardiovascular, Edwards Lifesciences, Medtronic, and NeoChord. Dr Kar has received consulting fees from Abbott, Boston Scientific, Medtronic, and W.L. Gore & Associates, and and has received grant support from Edwards Lifesciences and V-Wave. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Subjects
MESH: Mitral Valve Insufficiency, MESH: Humans, transcatheter edge-to-edge repair, MESH: Quality of Life, MESH: Reactive Oxygen Species, MitraClip system, MESH: Prospective Studies, mitral valve repair, MESH: Constriction, Pathologic, MESH: Cardiomyopathies, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, mitral regurgitation, TEER, MESH: Treatment Outcome
Abstract

Background: Anatomical and clinical criteria to define mitral transcatheter edge-to-edge repair (TEER) "unsuitability" have been proposed on the basis of a Heart Valve Collaboratory consensus opinion from physician experience with early-generation TEER devices but lacked an evidence-based approach.Objectives: The aim of this study was to explore the spectrum of TEER suitability using echocardiographic and clinical outcomes from the EXPAND G4 real-world postapproval study.Methods: EXPAND G4 is a global, prospective, multicenter, single-arm study that enrolled 1,164 subjects with mitral regurgitation (MR) treated with the MitraClip G4 System. Three groups were defined using the Heart Valve Collaboratory TEER unsuitability criteria: 1) risk of stenosis (RoS); 2) risk of inadequate MR reduction (RoIR); and 3) subjects with baseline moderate or less MR (MMR). A TEER-suitable (TS) group was defined by the absence of these characteristics. Endpoints included independent core laboratory-assessed echocardiographic characteristics, procedural outcomes, MR reduction, NYHA functional class, Kansas City Cardiomyopathy Questionnaire score, and major adverse events through 30 days.Results: Subjects in the RoS (n = 56), RoIR (n = 54), MMR (n = 326), and TS (n = 303) groups had high 30-day MR reduction rates (≤1+: RoS 97%, MMR 93%, and TS 91%; ≤2+: RoIR 94%). Thirty-day improvements in functional capacity (NYHA functional class I or II at 30 days vs baseline: RoS 94% vs 29%, RoIR 88% vs 30%, MMR 79% vs 26%, and TS 83% vs 33%) and quality of life (change in Kansas City Cardiomyopathy Questionnaire score: RoS +27 ± 26, RoIR +16 ± 26, MMR +19 ± 26, and TS +19 ± 24) were safely achieved in all groups, with low major adverse events (

Published
2023
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26. 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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27. Neutrophil extracellular traps have auto-catabolic activity and produce mononucleosome-associated circulating DNA

Author

Ekaterina Pisareva, Lucia Mihalovičová, Brice Pastor, Andrei Kudriavtsev, Alexia Mirandola, Thibault Mazard, Stephanie Badiou, Ulrich Maus, Lena Ostermann, Julia Weinmann-Menke, Elmo W. I. Neuberger, Perikles Simon, Alain R. Thierry, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut du Cancer de Montpellier (ICM), Comenius University in Bratislava, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), German Center for Lung Research, University Medical Center [Mainz], Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), and MORNET, Dominique

Subjects
Myeloperoxidase, Neutrophils, [SDV]Life Sciences [q-bio], Neutrophil, COVID-19, Genomics, Extracellular Traps, NET, [SDV] Life Sciences [q-bio], Mice, Nucleosome, Elastase, Genetics, Animals, Molecular Medicine, Circulating DNA, Cell-Free Nucleic Acids, Molecular Biology, Genetics (clinical)
Abstract

BackgroundBecause circulating DNA (cirDNA) are mainly detected as mononucleosome-associated circulating DNA (mono-N cirDNA) in blood apoptosis has until now been considered as the main source of cirDNA. The mechanism of cirDNA release into the circulation, however, is still not fully understood. This work addresses that knowledge gap, working from the postulate that neutrophil extracellular traps (NET) may be a source of cirDNA, and by investigating whether NET may directly produce mono-N cirDNAMethodsWe used the synergistic analytical information provided by specifically quantifying DNA by qPCR, and analyzing fragment size analysis by shallow WGS, and capillary electrophoresis to unequivocally study the following: thein vitrokinetics of cell derived genomic high molecular weight (gHMW) DNA degradation in serum; the production of extracellular DNA and NET markers such as neutrophil elastase (NE) and myeloperoxidase (MPO) byex vivoactivated neutrophils;in vitroNET degradation in serum. We also performed anin vivostudy in knockout mice, and anin vitrostudy of gHMW DNA degradation, to elucidate the role of NE and MPO in effecting DNA degradation and fragmentation. We then compared the NET associated markers and fragmentation size profiles of cirDNA in plasma obtained from patients with inflammatory diseases found to be associated with NET formation and high levels of cirDNA (COVID-19, N= 28; systemic lupus erythematosus, N= 10; metastatic colorectal cancer, N= 10; and from healthy individuals, N= 114).ResultsOur studies reveal that: gHMW DNA degradation in serum results in the accumulation of mono-N DNA (81.3% of the remaining DNA following 24H incubation in serum corresponded to mono-N DNA); “ex vivo” NET formation, as demonstrated by a concurrent 5-, 5- and 35-fold increase of NE, MPO, and cell-free DNA (cfDNA) concentration in PMA-activated neutrophil culture supernatant, leads to the release of high molecular weight DNA that degrades down to mono-N in serum; NET mainly in the form of gHMW DNA generate mono-N cirDNA (2% and 41% of the remaining DNA after 2 hours in serum corresponded to 1-10 kbp fragments and mono-N, respectively) independent of any cellular process when degraded in serum; NE and MPO may contribute synergistically to NET autocatabolism, resulting in a 25-fold decrease in total DNA concentration and a DNA fragment size profile similar to that observed from cirDNA following 8h incubation with both NE and MPO; the cirDNA size profile of NE KO mice significantly differed from that of the WT, suggesting NE involvement in DNA degradation; and a significant increase in the levels of NE, MPO and cirDNA was detected in plasma samples from lupus, COVID-19 and mCRC, showing a high correlation with these inflammatory diseases, while no correlation of NE and MPO with cirDNA was found in HI.ConclusionsOur work thus describes the mechanisms by which NET and cirDNA are linked, by demonstrating that NET are a major source of mono-N cirDNA independent of apoptosis, and thus establishing a new paradigm of the mechanisms of cirDNA release in normal and pathological conditions, as well as demonstrating a link between immune response and cirDNA.

Published
2022
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28. Baseline clusters and the response to positive airway pressure treatment in obstructive sleep apnoea patients: longitudinal data from the European Sleep Apnea Database cohort

Author

Yassen, Ashraf, Coboeken, Katrin, Bailly, Sébastien, Burghaus, Rolf, Buskova, Jitka, Dogas, Zoran, Drummond, Marta, Gouveris, Haralampos, Joppa, Pavol, Lippert, Joerg, Lombardi, Carolina, Mihaicuta, Stefan, Pépin, Jean Louis, Zou, Ding, Hedner, Jan, Grote, Ludger, Bayer Technology Services [Leverkusen], Hypoxie et PhysioPathologie (HP2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), CHU Grenoble, National Institute of Mental Health [Klecany, Czech Republic] (NIMH), University of Split, Hospital de São João [Porto], University Medical Center [Mainz], P.J. Safarik University, Univerzitnej nemocnice L. Pasteura Košice [Košice, Slovakia]. (UNLPK), Istituto Auxologico Italiano IRCCS Ospedale San Luca [Milan, Italy] (IAI), Victor Babeş University of Medicine and Pharmacy (UMFT), Sahlgrenska Academy at University of Gothenburg [Göteborg], Sahlgrenska University Hospital [Gothenburg], and SALAS, Danielle

Subjects
Pulmonary and Respiratory Medicine, [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], CARDIOVASCULAR EVENTS, PHENOTYPES, CPAP, ADHERENCE, DISEASE, OSA
Abstract

IntroductionThe European Sleep Apnea Database was used to identify distinguishable obstructive sleep apnoea (OSA) phenotypes and to investigate the clinical outcome during positive airway pressure (PAP) treatment.MethodProspective OSA patient data were recruited from 35 sleep clinics in 21 European countries. Unsupervised cluster analysis (anthropometrics, clinical variables) was performed in a random sample (n=5000). Subsequently, all patients were assigned to the clusters using a conditional inference tree classifier. Responses to PAP treatment change in apnoea severity and Epworth sleepiness scale (ESS) were assessed in relation to baseline patient clusters and at short- and long-term follow-up.ResultsAt baseline, 20 164 patients were assigned (mean age 54.1±12.2 years, 73% male, median apnoea–hypopnoea index (AHI) 27.3 (interquartile range (IQR) 14.1–49.3) events·h−1, and ESS 9.8±5.3) to seven distinct clusters based on anthropometrics, comorbidities and symptoms. At PAP follow-up (median 210 [IQR 134–465] days), the observed AHI reduction (n=1075) was similar, whereas the ESS response (n=3938) varied: largest reduction in cluster 3 (young healthy symptomatic males) and 6 (symptomatic males with psychiatric disorders, −5.0 and −5.1 units, respectively (all pConclusionOSA patients can be classified into clusters based on clinically identifiable features. Importantly, these clusters may be useful for prediction of both short- and long-term responses to PAP intervention.

Published
2022
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29. Sonidegib improved quality of life in patients with advanced basal cell carcinoma: results from the phase 2 Basal Cell Carcinoma Outcomes with LDE225 Treatment trial through 73 weeks

Author

Michael, Migden, Carmen, Loquai, Caroline, Robert, Jean-François, Baurain, Nicholas, Squittieri, Ramon, Arntz, Jörg, Dierlamm, Brigitte, Dréno, The University of Texas M.D. Anderson Cancer Center [Houston], University Medical Center [Mainz], Institut Gustave Roussy (IGR), Service de dermatologie, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Cliniques Universitaires Saint-Luc [Bruxelles], Université Catholique de Louvain = Catholic University of Louvain (UCL), Sun Pharmaceutical Industries, Inc. [Princeton, NJ, USA] (SPI), Sun Pharmaceutical Industries [Hoofddorp, North Holland, Netherlands] (SPI - (Europe) B.V.), Immunology and New Concepts in ImmunoTherapy (INCIT), Université d'Angers (UA)-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)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Service de dermatologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Pecqueret, Valérie

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], Dermatology
Abstract

International audience

Published
2022
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30. Development of fluorizoline analogues as prohibitin ligands that modulate C-RAF signaling, p21 expression and melanogenesis

Author

Nora Chouha, Hussein Abou-Hamdan, Hajime Yurugi, Riku Yoshii, Hiromi Ii, Ahmad Najem, Ghanem E. Ghanem, Susumu Nakata, Krishnaraj Rajalingam, Yu Peng, Dong Wang, Canan G. Nebigil, Laurent Désaubry, Nanomédecine Régénérative (NanoRegMed), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Biomédecine de Strasbourg (CRBS), Laboratoire de Chimie et Chimie de l'Environnement (LCCE), Université Hadj Lakhdar Batna 1, University Medical Center [Mainz], Kyoto University, Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Université libre de Bruxelles (ULB), Tianjin University of Science and Technology (TUST), Xinjiang University, and univOAK, Archive ouverte

Subjects
Cyclin-Dependent Kinase Inhibitor p21, Melanins, Pharmacology, Melanogenesis, p21, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, Organic Chemistry, Apoptosis, General Medicine, Heterocycles, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Protein Serine-Threonine Kinases, Ligands, Proto-Oncogene Proteins c-raf, Repressor Proteins, MAP kinases, Proto-Oncogene Proteins, Drug Discovery, Prohibitins, Humans, Chimie/Chimie thérapeutique, HeLa Cells, Transcription Factors, Cancer
Abstract

Fluorizoline is a cytotoxic trifluorothiazoline that targets the scaffold proteins prohibitins-1 and -2 (PHB1/2) to inhibit the kinase C-RAF and promote the expression of the cyclin-dependent kinase inhibitor p21 to induce cancer cell death. In melanocytes, fluorizoline also induces the synthesis of melanin. Herein we report the first structural requirement of fluorizoline analogues for these activities. We identified in particular some compounds that display enhanced anti-C-RAF and anti-MEK activities, and a higher cytotoxicity in HeLa cells compared to fluorizoline. These results provide a foundation for further optimization of PHB ligands for the treatment of cancers. We also discovered an analogue of fluorizoline that displays pharmacological effects opposed to those of fluorizoline and that can be used as a chemical tool to explore PHB signaling in cancers and other diseases.

Published
2022
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31. Proposal of a New Comprehensive Notation for Hepatectomy

Author

Shoji Kawakatsu, Sung-Gyu Lee, Itaru Endo, Massimo Malagó, Eduardo de Santibañes, Antonio D Pinna, Ronald P. DeMatteo, Wojciech G. Polak, Olivier Soubrane, René Adam, David A. Geller, Alfredo Guglielmi, Karim Boudjema, Tomoki Ebata, Tomoaki Kato, Silvio Nadalin, Michelle L. DeOliveira, Peter Lodge, Hauke Lang, Jiahong Dong, Bryan M. Clary, Daniel Cherqui, William C. Chapman, Pierre-Alain Clavien, Masato Nagino, Luca Aldrighetti, Nagino, M., Dematteo, R., Lang, H., Cherqui, D., Malago, M., Kawakatsu, S., Deoliveira, M. L., Adam, R., Aldrighetti, L., Boudjema, K., Chapman, W., Clary, B., de Santibanes, E., Dong, J., Ebata, T., Endo, I., Geller, D., Guglielmi, A., Kato, T., Lee, S. -G., Lodge, P., Nadalin, S., Pinna, A., Polak, W., Soubrane, O., Clavien, P. -A., Aichi Cancer Center Hospital, University of Pennsylvania [Philadelphia], University Medical Center [Mainz], Hôpital Paul Brousse, University College of London [London] (UCL), University hospital of Zurich [Zurich], CHU Pontchaillou [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES), University of California [San Diego] (UC San Diego), University of California, Nagoya University, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), University of Verona (UNIVR), Columbia University [New York], University of Ulsan, Cleveland Clinic, Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Pennsylvania, Université de Rennes (UR), University of California (UC), Università degli studi di Verona = University of Verona (UNIVR), and Surgery

Subjects
Liver surgery, [SDV]Life Sciences [q-bio], medicine.medical_treatment, MEDLINE, 030230 surgery, computer.software_genre, Notation, Terminology, 03 medical and health sciences, 0302 clinical medicine, Terminology as Topic, terminology, Humans, Hepatectomy, Medicine, ComputingMilieux_MISCELLANEOUS, business.industry, Liver, 030220 oncology & carcinogenesis, nomenclature, Surgery, Artificial intelligence, business, computer, Natural language processing
Abstract

International audience

Published
2021
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32. 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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33. Characteristics and outcomes of patients screened for transcatheter mitral valve implantation: 1-year results from the CHOICE-MI registry

Author

Ben Ali, Walid, Ludwig, Sebastian, Duncan, Alison, Weimann, Jessica, Nickenig, Georg, Tanaka, Tetsu, Coisne, Augustin, Vincentelli, Andre, Makkar, Raj, Webb, John G., Akodad, Mariama, Muller, David W.M., Praz, Fabien, Wild, Mirjam G., Hausleiter, Jörg, Goel, Sachin S., von Ballmoos, Moritz Wyler, Denti, Paolo, Chehab, Omar, Redwood, Simon, Dahle, Gry, Baldus, Stephan, Adam, Matti, Ruge, Hendrik, Lange, Rüdiger, Kaneko, Tsuyoshi, Leroux, Lionel, Dumonteil, Nicolas, Tchetche, Didier, Treede, Hendrik, Flagiello, Michele, Obadia, Jean Francois, Walther, Thomas, Taramasso, Maurizio, Søndergaard, Lars, Bleiziffer, Sabine, Rudolph, Tanja K., Fam, Neil, Kempfert, Joerg, Granada, Juan F., Tang, Gilbert H.L., von Bardeleben, Ralph Stephan, Conradi, Lenard, Modine, Thomas, Kalbacher, Daniel, Blankenberg, Stefan, Koell, Benedikt, Schofer, Niklas, Westermann, Dirk, Weber, Marcel, CarMeN, laboratoire, Montreal Heart Institute - Institut de Cardiologie de Montréal, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Cardiovascular Research Foundation [New York, NY, USA] (CRF), Royal Brompton Hospital, Heart Center Bonn [Bonn, Germany] (HCB), University Hospital Bonn, CHU Lille, Cedars-Sinai Medical Center, St. Paul’s Hospital - University of British Columbia [Vancouver, BC, Canada] (SPH-UBC), St. Vincent's Hospital, Sydney, Bern University Hospital [Berne] (Inselspital), Ludwig Maximilian University [Munich] (LMU), Houston Methodist Hospital [Houston, TX, USA], IRCCS Ospedale San Raffaele [Milan, Italy], Guy's and St Thomas' Hospital [London], Oslo University Hospital [Oslo], University Hospital of Cologne [Cologne], German Heart Center = Deutsches Herzzentrum München [Munich, Germany] (GHC), Brigham and Women’s Hospital [Boston, MA], Harvard Medical School [Boston] (HMS), CHU Bordeaux [Bordeaux], Clinique Pasteur [Toulouse], University Medical Center [Mainz], Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Frankfurt University Hospital, Heart Center Hirslanden = HerzZentrum Hirslanden [Zürich, Switzerland] (HCL), Hôpital national = Rigshospitalet [Copenhagen, Denmark] (HNC), Heart and Diabetes Center NRW [Bad Oeynhausen, Germany] (HDC), St. Michael's Hospital, Mount Sinai Hospital [New York City, NY, USA] (MSH), University Heart Center [Hamburg], CHOICE-MI Investigators: Daniel Kalbacher, Stefan Blankenberg, Benedikt Koell, Niklas Schofer, Dirk Westermann, Marcel Weber, Johanna Vogelhuber, François Pontana, Eric Van Belle, Sung-Han Yoon, Anthony Chuang, Robert H Boone, Paul Jansz, Ning Song, Sara Hungerford, Stephan Windecker, David Reineke, Michael Reardon, Neal S Kleiman, Alessandra Sala, Eustachio Agricola, Francesco Maisano, Ronak Rajani, Bernard Prendergast, Kjell A Rein, Maria I Koerber, Laurin Ochs, Keti Vitanova, Magdalena Erlebach, Pinak Shah, Morgan Harloff, Guillaume Bonnet, Mathieu Pernot, Melchior Jonveaux, Felix Kreidel, Tobias Ruf, Matteo Pozzi, Razvan Dragulescu, Tomas Holubec, Heike Strohschnitter, Claudia Walther, Alberto Pozzoli, Ivan Wong, Kai Friedrichs, Mark Peterson, Axel Unbehaun, Markus Kofler., Ben Ali, Walid, Ludwig, Sebastian, Duncan, Alison, Weimann, Jessica, Nickenig, Georg, Tanaka, Tetsu, Coisne, Augustin, Vincentelli, Andre, Makkar, Raj, Webb, John G, Akodad, Mariama, Muller, David W M, Praz, Fabien, Wild, Mirjam G, Hausleiter, Jörg, Goel, Sachin S, von Ballmoos, Moritz Wyler, Denti, Paolo, Chehab, Omar, Redwood, Simon, Dahle, Gry, Baldus, Stephan, Adam, Matti, Ruge, Hendrik, Lange, Rüdiger, Kaneko, Tsuyoshi, Leroux, Lionel, Dumonteil, Nicola, Tchetche, Didier, Treede, Hendrik, Flagiello, Michele, Obadia, Jean-Francoi, Walther, Thoma, Taramasso, Maurizio, Søndergaard, Lar, Bleiziffer, Sabine, Rudolph, Tanja K, Fam, Neil, Kempfert, Joerg, Granada, Juan F, Tang, Gilbert H L, von Bardeleben, Ralph Stephan, Conradi, Lenard, Modine, Thoma, and Agricola, Eustachio

Subjects
Heart Failure, Heart Valve Prosthesis Implantation, Cardiac Catheterization, Medical therapy, [SDV]Life Sciences [q-bio], 610 Medizin, Mitral valve surgery, Mitral Valve Insufficiency, 610 Medicine & health, [SDV] Life Sciences [q-bio], Treatment Outcome, 610 Medical sciences, Humans, Mitral Valve, Registries, Cardiology and Cardiovascular Medicine, Transcatheter mitral valve implantation, Transcatheter edge-to-edge repair, Mitral regurgitation
Abstract

AIMS Transcatheter mitral valve implantation (TMVI) represents a novel treatment option for patients with mitral regurgitation (MR) unsuitable for established therapies. The CHOICE-MI registry aimed to investigate outcomes of patients undergoing screening for TMVI. METHODS AND RESULTS From 05/2014 to 03/2021, patients with MR considered suboptimal candidates for transcatheter edge-to-edge repair (TEER) and at high risk for mitral valve surgery underwent TMVI screening at 26 centres. Characteristics and outcomes were investigated for patients undergoing TMVI and for TMVI-ineligible patients referred to bailout-TEER, high-risk surgery or medical therapy (MT). The primary composite endpoint was all-cause mortality or heart failure hospitalisation after 1 year. Among 746 patients included (78.5 years [IQR 72.0-83.0], EuroSCORE II 4.7% [IQR 2.7-9.7]), 229 patients (30.7%) underwent TMVI with ten different dedicated devices. At 1 year, residual MR ≤1+ was present in 95.2% and the primary endpoint occurred in 39.2% of patients treated with TMVI. In TMVI-ineligible patients (N = 517, 69.3%), rates of residual MR ≤1+ were 37.2%, 100.0% and 2.4% after bailout-TEER, high-risk surgery and MT, respectively. The primary endpoint at 1 year occurred in 28.8% of patients referred to bailout-TEER, in 42.9% of patients undergoing high-risk surgery and in 47.9% of patients remaining on MT. CONCLUSION This registry included the largest number of patients treated with TMVI to date. TMVI with ten dedicated devices resulted in predictable MR elimination and sustained functional improvement at 1 year. In TMVI-ineligible patients, bailout-TEER and high-risk surgery represented reasonable alternatives, while MT was associated with poor clinical and functional outcomes. This article is protected by copyright. All rights reserved.

Published
2022
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34. Effective Management of Severe Asthma with Biologic Medications in Adult Patients: A Literature Review and International Expert Opinion

Author

Andrea Matucci, Roland Buhl, Michael E. Wechsler, J. Mark FitzGerald, Ian D. Pavord, David A. Jackson, Jo A Douglass, Ignacio Dávila, Elisabeth H. Bel, Monica Kraft, Arnaud Bourdin, Njira L Lugogo, University Medical Center [Mainz], University of Amsterdam [Amsterdam] (UvA), 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), Universidad de Salamanca, University of Melbourne, Institute for Heart and Lung Health [Vancouver, BC, Canada], Guy's and St Thomas' Hospitals, University of Michigan [Ann Arbor], University of Michigan System, Careggi University Hospital [Florence, Italie], University of Oxford [Oxford], National Jewish Health, University of Arizona, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), University of British Columbia (UBC), Guy's and St Thomas' Hospital [London], University of Oxford, National Jewish Health (NJH), and Retiveau, Nolwenn

Subjects
Adult, severe asthma, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Nitric Oxide, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 03 medical and health sciences, 0302 clinical medicine, Quality of life (healthcare), Health care, medicine, Immunology and Allergy, Humans, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, Intensive care medicine, Expert Testimony, Asthma, Biological Products, algorithm, business.industry, medicine.disease, 3. Good health, Clinical trial, Clinical research, 030228 respiratory system, Exhalation, 030220 oncology & carcinogenesis, Exhaled nitric oxide, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Biomarker (medicine), Sputum, eosinophils, medicine.symptom, business, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology
Abstract

International audience; Severe asthma often remains uncontrolled despite effective treatments and evidence-based guidelines. A group of global experts in asthma and biologic medications from nine countries considered the most relevant clinical variables to manage severe asthma in adult patients and guide treatment choice. The resulting recommendations address the investigation of biomarker levels (blood eosinophil count along with fractional concentration of exhaled nitric oxide [FeNO]), clinical features (oral corticosteroid [OCS] dependency, specific comorbid disease entities associated with severe type 2 asthma), and safety considerations. Current evidence suggests that biomarkers, including both blood or sputum eosinophil counts as well as FeNO, add prognostic and predictive value and should be measured in all patients with severe asthma. OCS use is an important factor in biologic selection, especially given the documented ability of some biologics to reduce OCS dependency. Comorbid diseases and relevant safety considerations to each biologic should also be considered. More data are needed to determine whether biomarker profiles identify patients suited to one biologic versus another as limited data support differential predictors of response. Further prospective head-to-head trials and post hoc analyses of clinical trial data are warranted. The authors believe these recommendations have value as they offer expert opinion to assist health care providers in making difficult decisions regarding the quality of care in severe, type 2 asthma with biologic medications. They remain conditional and are based on limited data owing to a lack of head-to-head comparisons.

Published
2021
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35. Shedding Light on Hemostasis in Patients With Inflammatory Bowel Diseases

Author

Laurent Peyrin-Biroulet, Patrick Lacolley, Jeremy Lagrange, Véronique Regnault, Denis Wahl, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), University Medical Center [Mainz], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Faculté de Médecine [Nancy], Université de Lorraine (UL), and Service d'Hépato-gastro-entérologie [CHRU Nancy]

Subjects
[SDV]Life Sciences [q-bio], Fibrinogen, Inflammatory bowel disease, digestive system, Fibrin, 03 medical and health sciences, 0302 clinical medicine, Von Willebrand factor, medicine, Humans, Platelet, Blood Coagulation, Hemostasis, Crohn's disease, Hepatology, biology, business.industry, Fibrinolysis, Inflammatory Bowel Disease, Gastroenterology, Endothelial Cells, Thrombosis, Inflammatory Bowel Diseases, medicine.disease, digestive system diseases, 3. Good health, 030220 oncology & carcinogenesis, Immunology, biology.protein, 030211 gastroenterology & hepatology, business, medicine.drug
Abstract

International audience; Patients with inflammatory bowel diseases (IBD) have an increased risk of thrombosis, possibly due to changes in blood cells and molecules involved in hemostasis. They have increased platelet counts and reactivity as well as increased platelet-derived large extracellular vesicles. Coagulation is continuously activated in patients with IBD, based on measured markers of thrombin generation, and the anticoagulant functions of endothelial cells are damaged. Furthermore, fibrinogen is increased and fibrin clots are denser. However, pathogenesis of thrombosis in patients with IBD appears to differ from that of patients without IBD. Patients with IBD also take drugs that might contribute to risk of thrombosis, complicating the picture. We review the features of homeostasis that are altered in patients with IBD and possible mechanisms of this relationship.

Published
2021
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36. 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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37. A randomized phase 3 trial of auto vs. allo transplantation as part of first-line therapy in poor-risk peripheral T-NHL

Author

Martin Wilhelm, Bettina Altmann, Mathieu Leclerc, Laurence de Leval, Ulrich Keller, Arnaud Jaccard, Emmanuel Gyan, Olivier Tournilhac, Peter Reimer, Maike Nickelsen, Martin Dreyling, Jacques-Olivier Bay, Karin Bilger, Bernd Metzner, Andreas Viardot, Laurence Sanhes, Murielle Roussel, Philippe Gaulard, Marita Ziepert, Noel Milpied, Gandhi Damaj, Norbert Schmitz, Friederike Braulke, Walter Lindemann, Eva Maria Wagner-Drouet, Alain Delmer, Bertram Glass, Guillaume Cartron, Thierry Lamy, Krimo Bouabdallah, Viola Poeschel, Frank Kroschinsky, Birte Friedrichs, Lorenz Truemper, David Sibon, Peter Dreger, Andreas Rosenwald, Christian Gisselbrecht, Mathias Haenel, Anne Banos, Gerald Wulf, University Hospital Münster - Universitaetsklinikum Muenster [Germany] (UKM), Georg-August-University [Göttingen], Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Universität Leipzig [Leipzig], Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Limoges, Kliniken Essen-Mitte, University Medical Center [Mainz], Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Centre Hospitalier Saint Jean de Perpignan, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), 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 ), CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], University Hospital Carl Gustav Carus [Dresden, Germany], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Catholic Hospital = Katholisches Krankenhaus [Hagen], Universität Heidelberg [Heidelberg], Universitätsklinikum Ulm - University Hospital of Ulm, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), CHU Clermont-Ferrand, Helios-Klinikum Berlin-Buch, University Hospital Homburg, Institut d'Hématologie de Basse-Normandie (IHBN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, CHU Necker - Enfants Malades [AP-HP], Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Institut de Cancérologie de Strasbourg Europe (ICANS), Le CHCB, Centre Hospitalier de la Côte Basque, Hospital of Chemnitz, Klinikum der Universität [München], Klinikum Oldenburg, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Onkologie Lerchenfeld [Hamburg], CHU Estaing [Clermont-Ferrand], Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne (UCA), CIC Clermont Ferrand, Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-Centre de Pharmacologie Clinique, Georg-August-University = Georg-August-Universität Göttingen, Universität Leipzig, Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), 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 ), Julius-Maximilians-Universität Würzburg (JMU), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Universität Heidelberg [Heidelberg] = Heidelberg University, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier de la Côte Basque (CHCB), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Herrada, Anthony

Subjects
0301 basic medicine, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Vincristine, medicine.medical_specialty, Allogeneic transplantation, Immunology, CHOP, Biochemistry, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, International Prognostic Index, Autologous stem-cell transplantation, immune system diseases, Internal medicine, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Anaplastic large-cell lymphoma, Etoposide, Lymphoid Neoplasia, business.industry, Lymphoma, T-Cell, Peripheral, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Cell Biology, Hematology, medicine.disease, 3. Good health, Transplantation, 030104 developmental biology, surgical procedures, operative, business, human activities, 030215 immunology, medicine.drug
Abstract

Standard first-line therapy for younger patients with peripheral T-cell lymphoma consists of six courses of CHOP or CHOEP consolidated by high-dose therapy and autologous stem cell transplantation (AutoSCT). We hypothesized that consolidative allogeneic transplantation (AlloSCT) could improve outcome. 104 patients with nodal peripheral T-cell lymphoma except ALK+ ALCL, 18 to 60 years of age, all stages and IPI scores except stage 1 and aaIPI 0, were randomized to receive 4 x CHOEP and 1 x DHAP followed by high-dose therapy and AutoSCT or myeloablative conditioning and AlloSCT. The primary endpoint was event-free survival (EFS) at three years. After a median follow-up of 42 months, 3-year EFS of patients undergoing AlloSCT was 43% (95% confidence interval [CI]: 29%; 57%) as compared to 38% (95% CI: 25%; 52%) after AutoSCT. Overall survival at 3 years was 57% (95% CI: 43%; 71%) versus 70% (95% CI: 57%; 82%) after AlloSCT or AutoSCT, without significant differences between treatment arms. None of 21 responding patients proceeding to AlloSCT as opposed to 13 of 36 patients (36%) proceeding to AutoSCT relapsed. Eight of 26 patients (31%) and none of 41 patients died due to transplant-related toxicity after allogeneic and autologous transplantation, respectively. In younger patients with T-cell lymphoma standard chemotherapy consolidated by autologous or allogeneic transplantation results in comparable survival. The strong graft-versus-lymphoma effect after AlloSCT was counterbalanced by transplant-related mortality. CHO(E)P followed by AutoSCT remains the preferred treatment option for transplant-eligible patients. AlloSCT is the treatment of choice for relapsing patients also after AutoSCT.

Published
2021
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38. 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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39. The management of secondary mitral regurgitation in patients with heart failure: a joint position statement from the Heart Failure Association (HFA), European Association of Cardiovascular Imaging (EACVI), European Heart Rhythm Association (EHRA), and European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the ESC

Author

José Luis Zamorano, Serge Boveda, Marco Metra, Mitja Lainscak, Ewa A. Jankowska, Theresa McDonagh, Jeroen J. Bax, Christian Mueller, Petar M. Seferovic, Andrew J.S. Coats, Thor Edvardsen, Andreas Baumbach, John G.F. Cleland, Claudio Muneretto, Ottavio Alfieri, Thomas Deneke, Mandeep R. Mehra, Jean-François Obadia, Fabien Praz, Lars Lund, Frank Ruschitzka, Dimitrios Farmakis, Alec Vahanian, Gerhard Hindricks, Hein Heidbuchel, Gerasimos Filippatos, Johann Bauersachs, Christoph Leclercq, Jelena Čelutkienė, Wilfried Mullens, Jörg Hausleiter, Nathan Mewton, Ralph Stephan von Bardeleben, Bernard Prendergast, Nikolaos Dagres, Stephan Windecker, Volker Rudolph, Piotr Ponikowski, Stefan D. Anker, Warwick Medical School, University of Warwick [Coventry], German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Queen Mary University of London (QMUL), Yale University School of Medicine, IRCCS San Raffaele Scientific Institute [Milan, Italie], University Medical Center [Mainz], Hannover Medical School [Hannover] (MHH), Leiden University Medical Center (LUMC), Clinique Pasteur [Toulouse], Vilnius University [Vilnius], University of Glasgow, Universität Leipzig [Leipzig], University of Cyprus [Nicosia], National and Kapodistrian University of Athens (NKUA), University-Hospital Munich-Großhadern [München], University of Wrocław [Poland] (UWr), University of Ljubljana, CIC-IT Rennes, Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Karolinska University Hospital [Stockholm], King‘s College London, Harvard Medical School [Boston] (HMS), CIC CHU Lyon (inserm), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), University Hospital Basel [Basel], Ziekenhuis Oost-Limburg (ZOL), University of Brescia, Bern University Hospital [Berne] (Inselspital), Ruhr-Universität Bochum [Bochum], Université de Paris (UP), Universidad Carlos III de Madrid [Madrid] (UC3M), Oslo University Hospital [Oslo], Antwerp University Hospital [Edegem] (UZA), University of Belgrade [Belgrade], Guy's and St Thomas' Hospital [London], and Clinical sciences

Subjects
medicine.medical_specialty, Percutaneous, Functional mitral regurgitation, Heart failure, Secondary mitral regurgitation, Transcatheter mitral valve repair, 610 Medicine & health, 030204 cardiovascular system & hematology, law.invention, Special Article, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Mitral valve, medicine, AcademicSubjects/MED00200, 030212 general & internal medicine, Mitral regurgitation, Ejection fraction, business.industry, Guideline, medicine.disease, 3. Good health, medicine.anatomical_structure, Ventricle, Cardiology, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Human medicine, Cardiology and Cardiovascular Medicine, business
Abstract

Secondary (or functional) mitral regurgitation (SMR) occurs frequently in chronic heart failure (HF) with reduced left ventricular (LV) ejection fraction, resulting from LV remodelling that prevents coaptation of the valve leaflets. Secondary mitral regurgitation contributes to progression of the symptoms and signs of HF and confers worse prognosis. The management of HF patients with SMR is complex and requires timely referral to a multidisciplinary Heart Team. Optimization of pharmacological and device therapy according to guideline recommendations is crucial. Further management requires careful clinical and imaging assessment, addressing the anatomical and functional features of the mitral valve and left ventricle, overall HF status, and relevant comorbidities. Evidence concerning surgical correction of SMR is sparse and it is doubtful whether this approach improves prognosis. Transcatheter repair has emerged as a promising alternative, but the conflicting results of current randomized trials require careful interpretation. This collaborative position statement, developed by four key associations of the European Society of Cardiology—the Heart Failure Association (HFA), European Association of Percutaneous Cardiovascular Interventions (EAPCI), European Association of Cardiovascular Imaging (EACVI), and European Heart Rhythm Association (EHRA)—presents an updated practical approach to the evaluation and management of patients with HF and SMR based upon a Heart Team approach., Graphical abstract

Published
2021
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40. Heterogeneity of the pharmacologic treatment of allergic rhinitis in Europe based on MIDAS and OTCims platforms

Author

Torsten Zuberbier, Julia Saueressig, Joaquim Mullol, Glenis Scadding, João Fonseca, G. Walter Canonica, Eric Van Ganse, Claus Bachert, Bolesław Samoliński, Olga Lourenço, Oliver Pfaar, Philippe Devillier, Ann-Kathrin Stroh, Wienczyslawa Czarlewski, Jean Bousquet, Ludger Klimek, Elísio Costa, Piotr Kuna, Detlef Schroder-Bernhardi, Victoria Cardona, Sophie Scheire, Nhan Pham Thi, Institut Català de la Salut, [Bousquet J] Charité Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Berlin, Germany. Department of Dermatology and Allergy, Comprehensive Allergy Center, Berlin Institute of Health, Berlin, Germany. University Hospital Montpellier, Montpellier, France. MACVIA-France, Montpellier, France. [Schröder-Bernhardi D] IQVIA Consumer Health, Frankfurt, Germany. [Bachert C] Upper Airways Research Laboratory, ENT Dept, Ghent University Hospital, Ghent, Belgium. International Airway Research Center, First Affiliated Hospital Guangzou, Sun Yat-sen University, Guangzou, China. Division of ENT Diseases, CLINTEC, Karolinska Institutet, Stockholm, Sweden. Department of ENT Diseases, Karolinska University Hospital, Stockholm, Sweden. [Canonica GW] Personalized Medicine Asthma, & Allergy Clinic-Humanitas University & Research Hospital, IRCCS-Milano, Milano, Italy. [Cardona V] Servei d’Al·lergologia, Servei de Medicina Interna, Vall d'Hebron Hospital Universitari, Barcelona, Spain. ARADyAL Research Network, Barcelona, Spain. [Costa EM] UCIBIO, REQUINTE, Faculty of Pharmacy and Competence Center on Active and Healthy Ageing of University of Porto (Porto4Ageing), Porto, Portugal, Vall d'Hebron Barcelona Hospital Campus, uBibliorum, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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), IQVIA, Ghent University Hospital, Sun Yat-Sen University [Guangzhou] (SYSU), Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], IRCCS Istituto Nazionale dei Tumori [Milano], Vall d'Hebron University Hospital [Barcelona], Unidade de Ciencias Biomoleculares Aplicadas (UCIBIO), Requimte, Universidade do Porto = University of Porto-Departamento de Química (DQ), Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto = University of Porto-Departamento de Química (DQ), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Hôpital Foch [Suresnes], Universidade do Porto = University of Porto, University Medical Center [Mainz], Medical University of Łódź (MUL), University of Beira Interior [Portugal] (UBI), Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Philipps Universität Marburg = Philipps University of Marburg, Institut de Recherche Biomédicale des Armées (IRBA), Medical University of Warsaw - Poland, University College of London [London] (UCL), Health Service and Performance Research (HESPER), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, and Retiveau, Nolwenn

Subjects
0301 basic medicine, Allergy, IMPACT, Database analysis, Medications, costs, MESH: Allergy and Immunology, Medication, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Allergic rhinitis, 0302 clinical medicine, medications, MESH: Anti-Allergic Agents, Anti-Allergic Agents, Medicine and Health Sciences, Medicine, Immunology and Allergy, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, Practice Patterns, Physicians', health care economics and organizations, International market, Medication use, Units, enfermedades respiratorias::enfermedades nasales::rinitis::rinitis alérgica [ENFERMEDADES], Medicaments - Prescripció - Europa, Europe, MESH: Rhinitis, Allergic, [SDV.IMM]Life Sciences [q-bio]/Immunology, preparados farmacéuticos::medicamentos por prescripción [COMPUESTOS QUÍMICOS Y DROGAS], localizaciones geográficas::Europa (continente) [DENOMINACIONES GEOGRÁFICAS], MIDAS, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology, Rinitis - Tractament - Europa, Healthcare system, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immunology, Respiratory Tract Diseases::Nose Diseases::Rhinitis::Rhinitis, Allergic [DISEASES], Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Geographic Locations::Europe [GEOGRAPHICALS], Eu countries, PERSON-CENTERED CARE, Pharmacological treatment, 03 medical and health sciences, units, Environmental health, Allergy and Immunology, MANAGEMENT, Humans, Pharmaceutical Preparations::Prescription Drugs [CHEMICALS AND DRUGS], MESH: Humans, allergic rhinitis, OTC Medicines, business.industry, PATHWAYS, Al·lèrgia - Tractament - Europa, AIR-POLLUTION, medicine.disease, Rhinitis, Allergic, Costs, 030104 developmental biology, 030228 respiratory system, Analytics, Family medicine, MESH: Practice Patterns, Physicians', ASTHMA, MESH: Europe, business
Abstract

Rinitis al·lèrgica; Costos; Medicaments Rinitis alérgica; Costos; Medicamentos Allergic rhinitis; Costs; Medications Background The practice of allergology varies widely between countries, and the costs and sales for the treatment of rhinitis differ depending on practices and health systems. To understand these differences and their implications, the rhinitis market was studied in some of the EU countries. Methods We conducted a pharmaco-epidemiological database analysis to assess the medications that were being prescribed for allergic rhinitis in the years 2016, 2017 and 2018. We used the IQVIA platforms for prescribed medicines (MIDAS®—Meaningful Integration of Data, Analytics and Services) and for OTC medicines (OTC International Market Tracking—OTCims). We selected the five most important markets in the EU (France, Germany, Italy, Poland and Spain). Results Intranasal decongestants were excluded from the analyses because they are rarely prescribed for allergic rhinitis. For both Standard Units (SU) and costs, France is leading the other countries. In terms of SU, the four other countries are similar. For costs, Poland is lower than the three others. However, medication use differs largely. For 2018, in SU, intranasal corticosteroid is the first treatment in Poland (70.0%), France (51.3%), Spain (51.1%) and Germany (50.3%), whereas the Italian market is dominated by systemic antihistamines (41.4%) followed by intranasal corticosteroids (30.1%). Results of other years were similar. Discussion There are major differences between countries in terms of rhinoconjunctivitis medication usage.

Published
2021
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41. A collaborative resource platform for non-human primate neuroimaging

Author

Rogier B. Mars, Benjamin Jung, Ting Xu, Cirong Liu, R. Austin Benn, Jordy Tasserie, Henry C. Evrard, Adam Messinger, Steven Giavasis, Michael P. Milham, Kep Kee Loh, Bastien Cagna, Pamela Garcia-Saldivar, Daniel R. Glen, Marcello G. P. Rosa, Lynn Uhrig, Jakob Seidlitz, Hugo Merchant, Rakshit Dadarwal, Xindi Wang, Paul A. Taylor, Eduardo A. Garza-Villarreal, Nikoloz Sirmpilatze, Caleb Sponheim, P. Christiaan Klink, Claude Lepage, Renée Hartig, Roberto Toro, Daniel S. Margulies, Katja Heuer, Julien Sein, Piotr Majka, Fondation pour la recherche médicale (Francia), Fondation de France (Francia), Human Brain Project, Biotechnology and Biological Sciences Research Council (Reino Unido), Wellcome Trust, National Institute of Mental Health (NIMH), German Primate Center - Deutsches Primatenzentrum -- Leibniz Insitute for Primate Research -- [Göttingen, Allemagne] (GPC - DPZ), Georg-August-University = Georg-August-Universität Göttingen, Max Planck Institute for Human Cognitive and Brain Sciences [Leipzig] (IMPNSC), Max-Planck-Gesellschaft, Centre de Recherche Interdisciplinaire / Center for Research and Interdisciplinarity [Paris, France] (CRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institute of Language, Communication and the Brain (ILCB), Wellcome Trust Centre for Integrative Neuroimaging (WIN - FMRIB), University of Oxford, Donders Institute for Brain, Cognition and Behaviour, Radboud University [Nijmegen], Child Mind Institute, Brown University, Children’s Hospital of Philadelphia (CHOP ), University of Pennsylvania, Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM), University of Chicago, Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada], Centro Nacional de Investigaciones Cardiovasculares Carlos III [Madrid, Spain] (CNIC), Instituto de Salud Carlos III [Madrid] (ISC), University of Tübingen, Max Planck Institute for Biological Cybernetics, Nathan S. Kline Institute for Psychiatric Research (NKI), New York State Office of Mental Health, Chinese Academy of Sciences [Beijing] (CAS), University Medical Center [Mainz], University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), Nencki Institute of Experimental Biology, Polska Akademia Nauk = Polish Academy of Sciences (PAN), Monash University [Clayton], Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Neuroimagerie cognitive - Psychologie cognitive expérimentale (UNICOG-U992), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre Neurosciences intégratives et Cognition (INCC - UMR 8002), Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Netherlands Institute for Neuroscience (NIN), Royal Netherlands Academy of Arts and Sciences (KNAW), This research was supported in part by the Intramural Research Program of the NIMH and utilized the computational resources of the NIH HPC Biowulf cluster (http://hpc.nih.gov). Pypreclin work was supported by the Fondation pour la Recherche Medicale (FRM grant number ECO20160736100 to JT), Fondation de France, Human Brain Project (Corticity project). RT and KH are supported by ANR-19-DATA-0025-01 NeuroWebLab. RBM is supported by the Biotechnology and Biological Sciences Research Council (BBSRC) UK [BB/N019814/1]. The Wellcome Centre for Integrative Neuroimaging is supported by core funding from the Wellcome Trust [203129/Z/16/Z]., ANR-19-DATA-0025,NeuroWebLab,Un laboratoire de neuroscience collectif: Au delà de FAIR(2019), Fondation pour la recherche médicale, Fondation de France, Biotechnology and Biological Sciences Research Council (United Kingdom), University of Göttingen - Georg-August-Universität Göttingen, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), University of Oxford [Oxford], Radboud university [Nijmegen], University of Pennsylvania [Philadelphia], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Universidad Nacional Autónoma de México (UNAM), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Saclay (COmUE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Loh, Kep Kee, and Un laboratoire de neuroscience collectif: Au delà de FAIR - - NeuroWebLab2019 - ANR-19-DATA-0025 - DONNEES - VALID

Subjects
Primates, Computer science, Cognitive Neuroscience, [SDV]Life Sciences [q-bio], Neuroimaging, Online Systems, 050105 experimental psychology, lcsh:RC321-571, Access to Information, Diffusion, 03 medical and health sciences, 0302 clinical medicine, Resource (project management), Structural, Pipeline, Animals, 0501 psychology and cognitive sciences, MESH: Animals, MESH: Neuroimaging, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Non human primate, Functional, Action, intention, and motor control, Resource sharing, 05 social sciences, Data science, MESH: Online Systems, MESH: Access to Information, [SDV] Life Sciences [q-bio], MESH: Primates, Neurology, Open science, Toolbox, 030217 neurology & neurosurgery
Abstract

Neuroimaging non-human primates (NHPs) is a growing, yet highly specialized field of neuroscience. Resources that were primarily developed for human neuroimaging often need to be significantly adapted for use with NHPs or other animals, which has led to an abundance of custom, in-house solutions. In recent years, the global NHP neuroimaging community has made significant efforts to transform the field towards more open and collaborative practices. Here we present the PRIMatE Resource Exchange (PRIME-RE), a new collaborative online platform for NHP neuroimaging. PRIME-RE is a dynamic community-driven hub for the exchange of practical knowledge, specialized analytical tools, and open data repositories, specifically related to NHP neuroimaging. PRIME-RE caters to both researchers and developers who are either new to the field, looking to stay abreast of the latest developments, or seeking to collaboratively advance the field . Pypreclin work was supported by the Fondation pour la Recherche Medicale (FRM grant number ECO20160736100 to JT), Fondation de France, Human Brain Project (Corticity project). RT and KH are supported by ANR-19-DATA-0025-01 NeuroWebLab. RBM is supported by the Biotechnology and Biological Sciences Research Council (BBSRC) UK [BB/N019814/1]. The Wellcome Centre for Integrative Neuroimaging is supported by core funding from the Wellcome Trust [203129/Z/16/Z]. Sí

Published
2021
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42. The structural heart disease interventional imager rationale, skills and training: a position paper of the European Association of Cardiovascular Imaging

Author

Francesco Faletra, Eustachio Agricola, Hani Mahmoud-Elsayed, Nina Ajmone Marsan, Ralph Stephan von Bardeleben, Marc R. Dweck, Erwan Donal, Mark J. Monaghan, Thor Edvardsen, Francesco Ancona, Bogdan A. Popescu, Pal Maurovich-Hovart, José Luis Zamorano, Nina Wunderlich, Martin J. Swaans, Bernard Cosyns, Patrizio Lancellotti, Leyla Elif Sade, José M. C. Ribeiro, Eric Brochet, Agricola, Eustachio, Ancona, Francesco, Brochet, Eric, Donal, Erwan, Dweck, Marc, Faletra, Francesco, Lancellotti, Patrizio, Mahmoud-Elsayed, Hani, Marsan, Nina Ajmone, Maurovich-Hovart, Pal, Monaghan, Mark, Ribeiro, José, Sade, Leyla Elif, Swaans, Martin, Von Bardeleben, Ralph Stephan, Wunderlich, Nina, Zamorano, Jose-Lui, Popescu, Bogdan A, Cosyns, Bernard, Edvardsen, Thor, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Ospedale San Raffaele, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], University of Edinburgh, Cardiocentro Ticino [Lugano], Universität Zürich [Zürich] = University of Zurich (UZH), Università degli studi di Bari Aldo Moro (UNIBA), Leiden University Medical Center (LUMC), Semmelweis University of Medicine [Budapest], King‘s College London, Başkent University Hospital [Adana, Turkey], St. Antonius Hospital [Nieuwegein], University Medical Center [Mainz], Hospital Universitario Ramón y Cajal [Madrid], Universidad de Alcalá - University of Alcalá (UAH), Université de Médecine Carol Davila, Universitair Ziekenhus Brussel (UZ Brussel), Oslo University Hospital [Oslo], Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Universitair Ziekenhuis Brussel = University Hospital of Brussels (UZ Brussel), Jonchère, Laurent, Clinical sciences, Cardio-vascular diseases, Cardiology, and Universiteit Leiden

Subjects
medicine.medical_specialty, Cardiac Catheterization, Certification, Heart Diseases, education, Psychological intervention, Context (language use), 030204 cardiovascular system & hematology, Subspecialty, Interventional imaging, Multimodality, 03 medical and health sciences, 0302 clinical medicine, medicine, Medical imaging, Humans, Radiology, Nuclear Medicine and imaging, Medical physics, 030212 general & internal medicine, Structural heart disease, Cardiac imaging, [SDV.IB] Life Sciences [q-bio]/Bioengineering, business.industry, General Medicine, Percutaneous treatment of structural heart disease, 3. Good health, Cardiac Imaging Techniques, Position paper, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Cardiology and Cardiovascular Medicine, business
Abstract

Percutaneous therapeutic options for an increasing variety of structural heart diseases (SHD) have grown dramatically. Within this context of continuous expansion of devices and procedures, there has been increased demand for physicians with specific knowledge, skills, and advanced training in multimodality cardiac imaging. As a consequence, a new subspecialty of ‘Interventional Imaging’ for SHD interventions and a new dedicated professional figure, the ‘Interventional Imager’ with specific competencies has emerged. The interventional imager is an integral part of the heart team and plays a central role in decision-making throughout the patient pathway, including the appropriateness and feasibility of a procedure, pre-procedural planning, intra-procedural guidance, and post-procedural follow-up. However, inherent challenges exist to develop a training programme for SHD imaging that differs from traditional cardiovascular imaging pathways. The purpose of this document is to provide the standard requirements for the training in SHD imaging, as well as a starting point for an official certification process for SHD interventional imager.

Published
2021
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43. Synthesis, Molecular Docking and Biological Characterization of Pyrazine Linked 2-Aminobenzamides as New Class I Selective Histone Deacetylase (HDAC) Inhibitors with Anti-Leukemic Activity

Author

Hany S. Ibrahim, Mohamed Abdelsalam, Yanira Zeyn, Matthes Zessin, Al-Hassan M. Mustafa, Marten A. Fischer, Patrik Zeyen, Ping Sun, Emre F. Bülbül, Anita Vecchio, Frank Erdmann, Matthias Schmidt, Dina Robaa, Cyril Barinka, Christophe Romier, Mike Schutkowski, Oliver H. Krämer, Wolfgang Sippl, univOAK, Archive ouverte, Martin-Luther-Universität Halle Wittenberg (MLU), University Medical Center [Mainz], University of Aswan, Institute of Biotechnology of the Czech Academy of Sciences (IBT / CAS), Czech Academy of Sciences [Prague] (CAS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), and Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Pyridines, QH301-705.5, Proton Magnetic Resonance Spectroscopy, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, histone deacetylases, HDAC1, HDAC2, HDAC3, 2-aminobenzamides, SAR studies, acute myeloid leukemia (AML), docking, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Article, Catalysis, Inorganic Chemistry, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, Humans, ortho-Aminobenzoates, Physical and Theoretical Chemistry, Biology (General), Molecular Biology, QD1-999, Spectroscopy, Organic Chemistry, General Medicine, Computer Science Applications, Histone Deacetylase Inhibitors, Molecular Docking Simulation, Chemistry, HEK293 Cells, Pyrazines, Benzamides
Abstract

Class I histone deacetylases (HDACs) are key regulators of cell proliferation and they are frequently dysregulated in cancer cells. We report here the synthesis of a novel series of class-I selective HDAC inhibitors (HDACi) containing a 2-aminobenzamide moiety as a zinc-binding group connected with a central (piperazin-1-yl)pyrazine or (piperazin-1-yl)pyrimidine moiety. Some of the compounds were additionally substituted with an aromatic capping group. Compounds were tested in vitro against human HDAC1, 2, 3, and 8 enzymes and compared to reference class I HDACi (Entinostat (MS-275), Mocetinostat, CI994 and RGFP-966). The most promising compounds were found to be highly selective against HDAC1, 2 and 3 over the remaining HDAC subtypes from other classes. Molecular docking studies and MD simulations were performed to rationalize the in vitro data and to deduce a complete structure activity relationship (SAR) analysis of this novel series of class-I HDACi. The most potent compounds, including 19f, which blocks HDAC1, HDAC2, and HDAC3, as well as the selective HDAC1/HDAC2 inhibitors 21a and 29b, were selected for further cellular testing against human acute myeloid leukemia (AML) and erythroleukemic cancer (HEL) cells, taking into consideration their low toxicity against human embryonic HEK293 cells. We found that 19f is superior to the clinically tested class-I HDACi Entinostat (MS-275). Thus, 19f is a new and specific HDACi with the potential to eliminate blood cancer cells of various origins.

Published
2021
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44. The European NAFLD Registry: A real-world longitudinal cohort study of nonalcoholic fatty liver disease

Author

Hardy, Timothy, Wonders, Kristy, Younes, Ramy, Aithal, Guruprasad P, Aller, Rocio, Allison, Michael, Bedossa, Pierre, Betsou, Fay, Boursier, Jerome, Brosnan, M Julia, Burt, Alastair, Cobbold, Jeremy, Cortez-Pinto, Helena, Day, Chris P, Dufour, Jean-Francois, Ekstedt, Mattias, Francque, Sven, Harrison, Stephen, Miele, Luca, Nasr, Patrik, Papatheodoridis, George, Petta, Salvatore, Tiniakos, Dina, Torstenson, Richard, Valenti, Luca, Holleboom, Adriaan G, Yki-Jarvinen, Hannele, Geier, Andreas, Romero-Gomez, Manuel, Ratziu, Vlad, Bugianesi, Elisabetta, Schattenberg, Jörn M, Anstee, Quentin M, LITMUS Consortium, Newcastle University [Newcastle], Università degli studi di Torino (UNITO), University of Nottingham, UK (UON), Universidad de Valladolid [Valladolid] (UVa), Cambridge University Hospitals - NHS (CUH), University of Cambridge [UK] (CAM), Integrated BioBank of Luxembourg (IBBL), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Pfizer, Oxford University Hospitals NHS Trust, University of Oxford [Oxford], Universidade de Lisboa (ULISBOA), University of Bern, Linköping University (LIU), University of Antwerp (UA), Università cattolica del Sacro Cuore [Roma] (Unicatt), National and Kapodistrian University of Athens (NKUA), Università degli studi di Palermo - University of Palermo, University of Milan, University of Helsinki, University of Würzburg, Hospital Universitario Virgen del Rocío [Sevilla], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), University Medical Center [Mainz], Newcastle Upon Tyne Hospitals NHS Foundation Trust, Vascular Medicine, ACS - Diabetes & metabolism, ACS - Amsterdam Cardiovascular Sciences, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, LITMUS Consortium, Innovative Medicines Initiative, European Commission, Department of Medicine, HUS Internal Medicine and Rehabilitation, Helsinki University Hospital Area, Hardy T., Wonders K., Younes R., Aithal G.P., Aller R., Allison M., Bedossa P., Betsou F., Boursier J., Brosnan M.J., Burt A., Cobbold J., Cortez-Pinto H., Day C.P., Dufour J.-F., Ekstedt M., Francque S., Harrison S., Miele L., Nasr P., Papatheodoridis G., Petta S., Tiniakos D., Torstenson R., Valenti L., Holleboom A.G., Yki-Jarvinen H., Geier A., Romero-Gomez M., Ratziu V., Bugianesi E., Schattenberg J.M., Anstee Q.M., Harrison, Seamus Conor [0000-0003-1480-1143], and Apollo - University of Cambridge Repository

Subjects
Liver Cirrhosis, PROGNOSIS, Cirrhosis, SCORING SYSTEM, [SDV]Life Sciences [q-bio], PROGRESSION, Disease, Biomarker, Cirrhosis, NAFLD, NASH, STEATOHEPATITIS, DEFINITIONS, Cohort Studies, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, Nonalcoholic fatty liver disease, Pharmacology (medical), 030212 general & internal medicine, Longitudinal Studies, Registries, ComputingMilieux_MISCELLANEOUS, media_common, Pharmacology. Therapy, Fatty liver, Liver Neoplasms, NASH, General Medicine, 3. Good health, Liver, 317 Pharmacy, Cohort, 0305 other medical science, Cohort study, medicine.medical_specialty, Settore MED/12 - GASTROENTEROLOGIA, Geriatrik, QUESTIONNAIRE, NAFLD, Biomarker, 610 Medicine & health, 03 medical and health sciences, medicine, STEATOSIS, media_common.cataloged_instance, Humans, ALGORITHM, European union, Intensive care medicine, 030505 public health, business.industry, CONSUMPTION, STAGING SYSTEM, medicine.disease, Diabetes Mellitus, Type 2, Geriatrics, 3121 General medicine, internal medicine and other clinical medicine, 3111 Biomedicine, Human medicine, Steatohepatitis, business
Abstract

© 2020 The Author(s)., Non-Alcoholic Fatty Liver Disease (NAFLD), a progressive liver disease that is closely associated with obesity, type 2 diabetes, hypertension and dyslipidaemia, represents an increasing global public health challenge. There is significant variability in the disease course: the majority exhibit only fat accumulation in the liver but a significant minority develop a necroinflammatory form of the disease (non-alcoholic steatohepatitis, NASH) that may progress to cirrhosis and hepatocellular carcinoma. At present our understanding of pathogenesis, disease natural history and long-term outcomes remain incomplete. There is a need for large, well characterised patient cohorts that may be used to address these knowledge gaps and to support the development of better biomarkers and novel therapies. The European NAFLD Registry is an international, prospectively recruited observational cohort study that aims to establish a large, highly-phenotyped patient cohort and linked bioresource. Here we describe the infrastructure, data management and monitoring plans, and the standard operating procedures implemented to ensure the timely and systematic collection of high-quality data and samples. Already recruiting subjects at secondary/tertiary care centres across Europe, the Registry is supporting the European Union IMI2-funded LITMUS ‘Liver Investigation: Testing Marker Utility in Steatohepatitis’ consortium, which is a major international effort to robustly validate biomarkers that diagnose, risk stratify and/or monitor NAFLD progression and liver fibrosis stage. The European NAFLD Registry has the demonstrable capacity to support research and biomarker development at scale and pace., The European NAFLD Registry is supported by the LITMUS (Liver Investigation: Testing Biomarker Utility in Steatohepatitis) consortium funded by the European Union Innovative Medicines Initiative 2 (IMI2) Joint Undertaking under grant agreement 777377, which receives support from the Horizon 2020 Framework Program of European Union and EFPIA. It has also received support from the EPoS (Elucidating Pathways of Steatohepatitis) consortium funded by the Horizon 2020 Framework Program of the European Union under Grant Agreement 634413, the FLIP consortium funded by the Framework Program 7 of the European Union under grant agreement 241762, and an EASL Registry Grant from the European Association for the Study of the Liver.

Published
2020
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45. Effect of high-caloric nutrition on serum neurofilament light chain levels in amyotrophic lateral sclerosis

Author

Torsten Grehl, Bertold Schrank, Johannes Dorst, Matthias Boentert, Jens Dreyhaupt, Daniel Zeller, Susanne Petri, Markus Otto, Franceso Roselli, Julian Grosskreutz, Thomas Meyer, Joachim Schuster, Andreas Hermann, Luc Dupuis, Simon Witzel, Andrea Sylvia Winkler, Johannes Prudlo, Stanislav Gorbulev, Ulrike Weiland, Jochen H. Weishaupt, Berit Jordan, Albert C. Ludolph, Jan Kassubek, University of Ulm (UUlm), Hannover Medical School [Hannover] (MHH), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Ruhr-Universität Bochum [Bochum], Technische Universität Dresden = Dresden University of Technology (TU Dresden), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), University of Rostock, Martin-Luther-University Halle-Wittenberg, Heidelberg University Hospital [Heidelberg], Jena University Hospital [Jena], University of Würzburg = Universität Würzburg, University of Münster, DKD Helios Klinik Wiesbaden [Wiesbaden, Germany] (DKD HELIOS Medical Center), University Medical Center Rostock, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), University Medical Center [Mainz], Mécanismes Centraux et Périphériques de la Neurodégénérescence, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Technical University of Munich (TUM), Westfälische Wilhelms-Universität Münster = University of Münster (WWU), and Dieterle, Stéphane

Subjects
Male, medicine.medical_specialty, Neurofilament, [SDV]Life Sciences [q-bio], blood [Neurofilament Proteins], Placebo, Diet, High-Fat, Gastroenterology, 03 medical and health sciences, blood [Amyotrophic Lateral Sclerosis], 0302 clinical medicine, Neurofilament Proteins, Internal medicine, Post-hoc analysis, medicine, Humans, ddc:610, Amyotrophic lateral sclerosis, MESH: Neurofilament Proteins, ComputingMilieux_MISCELLANEOUS, MESH: Amyotrophic Lateral Sclerosis, Randomized Controlled Trials as Topic, MESH: Humans, MESH: Middle Aged, business.industry, Therapeutic effect, Amyotrophic Lateral Sclerosis, Middle Aged, medicine.disease, MESH: Male, 3. Good health, Riluzole, [SDV] Life Sciences [q-bio], Psychiatry and Mental health, MESH: Diet, High-Fat, MESH: Randomized Controlled Trials as Topic, Tolerability, statistics & numerical data [Randomized Controlled Trials as Topic], motor neuron disease, Population study, Surgery, Female, Neurology (clinical), business, MESH: Female, 030217 neurology & neurosurgery, medicine.drug
Abstract

Recent publications showed that circulating neurofilaments (Nfs) may be used as a diagnostic biomarker distinguishing amyotrophic lateral sclerosis (ALS) from ALS mimics with high sensitivity and specificity.1–3 Furthermore, it has been shown that patients with higher Nf levels show faster disease progression1 and shorter survival.2 3 Nf levels remain rather stable during the course of disease.2 Current literature suggests that the diagnostic value of neurofilament light chains (NfL) and phosphorylated neurofilament heavy chains in cerebrospinal fluid is about equal, whereas in blood NfL seems to be superior.4 In this study, we investigated the effect of a high-caloric fatty diet (HCFD) on NfL serum levels, using blood samples collected during the LIPCAL-ALS (efficacy, safety and tolerability of high lipid and caloriesupplementation in amyotrophic lateral sclerosis) study, a randomised, double-blind, parallel-group, placebo-controlled, multicentre trial, which investigated the therapeutic effect of HCFD in ALS.5 In LIPCAL-ALS, 201 patients (80 women, 121 men, age 62.4±10.8) were randomly assigned (1:1) to receive either HCFD (405 kcal/day, 100% fat) or placebo in addition to riluzole (100 mg/day) for 18 months. Although the primary outcome overall survival was negative in the whole study population (p=0.44), the post hoc analysis revealed a significantly longer survival for fast-progressing patients (ie, patients with an Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) slope >median between disease onset and baseline) in the HCFD group compared with placebo.5 To further corroborate our hypothesis of a disease-modifying effect of HCFD, we analysed NfL serum levels from LIPCAL-ALS participants. At each on-site visit during LIPCAL-ALS (6-month intervals), patients were asked if they were willing to provide an additional serum sample for NfL analysis on a voluntary basis. Serum NfL concentrations were measured with the single molecule array (Simoa) platform provided by Quanterix (Lexington, Massachusetts, USA) with single measurements …

Published
2020
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46. Impact of renal function on clinical outcomes after PCI in ACS and stable CAD patients treated with ticagrelor: a prespecified analysis of the GLOBAL LEADERS randomized clinical trial

Author

Hideyuki Kawashima, Scot Garg, Chao Gao, Hironori Hara, Nick Curzen, Dominika Klimczak-Tomaniak, Christian W. Hamm, Dominick J. Angiolillo, Marco Valgimigli, Pascal Vranckx, Richard Anderson, Norihiro Kogame, Davide Capodanno, Masafumi Ono, Rutao Wang, Ply Chichareon, Rodrigo Modolo, Michael Haude, Mariusz Tomaniak, Yoshinobu Onuma, Janusz Kochman, Robert F. Storey, Tessa Rademaker-Havinga, Tommaso Gori, Stephan Windecker, Gilles Montalescot, Patrick W. Serruys, Kuniaki Takahashi, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Medical University of Warsaw - Poland, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), University of Campinas [Campinas] (UNICAMP), Xijing Hospital, Radboud university [Nijmegen], University Medical Center [Mainz], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Catania [Italy], University of Sheffield [Sheffield], Bern University Hospital [Berne] (Inselspital), National University of Ireland [Galway] (NUI Galway), Imperial College London, National Heart and Lung Institute [London] (NHLI), Royal Brompton and Harefield NHS Foundation Trust-Imperial College London, University of Wales, ACS - Atherosclerosis & ischemic syndromes, ACS - Microcirculation, Graduate School, Cardiology, ACS - Heart failure & arrhythmias, University of Zurich, and Serruys, Patrick W

Subjects
Male, Acute coronary syndrome, medicine.medical_specialty, Ticagrelor, Impaired renal function, medicine.medical_treatment, Aspirin-free antiplatelet strategies, [SDV]Life Sciences [q-bio], 610 Medicine & health, Coronary Artery Disease, 030204 cardiovascular system & hematology, 11171 Cardiocentro Ticino, 2705 Cardiology and Cardiovascular Medicine, Percutaneous coronary intervention, Coronary artery disease, 03 medical and health sciences, Chronic kidney disease, DAPT, 0302 clinical medicine, Internal medicine, medicine, Clinical endpoint, Humans, 030212 general & internal medicine, Myocardial infarction, Renal Insufficiency, Acute Coronary Syndrome, Aged, business.industry, Dual Anti-Platelet Therapy, Hazard ratio, Drug-Eluting Stents, General Medicine, Middle Aged, medicine.disease, 3. Good health, Treatment Outcome, Conventional PCI, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, Platelet Aggregation Inhibitors, medicine.drug, Glomerular Filtration Rate
Abstract

Background: Impaired renal function (IRF) is associated with increased risks of both ischemic and bleeding events. Ticagrelor has been shown to provide greater absolute reduction in ischemic risk following acute coronary syndrome (ACS) in those with versus without IRF. Methods: A pre-specified sub-analysis of the randomized GLOBAL LEADERS trial (n = 15,991) comparing the experimental strategy of 23-month ticagrelor monotherapy (after 1-month ticagrelor and aspirin dual anti-platelet therapy [DAPT]) with 12-month DAPT followed by 12-month aspirin after percutaneous coronary intervention (PCI) in ACS and stable coronary artery disease (CAD) patients stratified according to IRF (glomerular filtration rate < 60 ml/min/1.73 m 2). Results: At 2 years, patients with IRF (n = 2171) had a higher rate of the primary endpoint (all-cause mortality or centrally adjudicated, new Q-wave myocardial infarction [MI](hazard ratio [HR] 1.64, 95% confidence interval [CI] 1.35–1.98, p adj = 0.001), all-cause death, site-reported MI, all revascularization and BARC 3 or 5 type bleeding, compared with patients without IRF. Among patients with IRF, there were similar rates of the primary endpoint (HR 0.82, 95% CI 0.61–1.11, p = 0.192, p int = 0.680) and BARC 3 or 5 type bleeding (HR 1.10, 95% CI 0.71–1.71, p = 0.656, p int = 0.506) in the experimental versus the reference group. No significant interactions were seen between IRF and treatment effect for any of the secondary outcome variables. Among ACS patients with IRF, there were no between-group differences in the rates of the primary endpoint or BARC 3 or 5 type bleeding; however, the rates of the patient-oriented composite endpoint (POCE) of all-cause death, any stroke, MI, or revascularization (p int = 0.028) and net adverse clinical events (POCE and BARC 3 or 5 type bleeding) (p int = 0.045), were lower in the experimental versus the reference group. No treatment effects were found in stable CAD patients categorized according to presence of IRF. Conclusions: IRF negatively impacted long-term prognosis after PCI. There were no differential treatment effects found with regard to all-cause death or new Q-wave MI after PCI in patients with IRF treated with ticagrelor monotherapy. Clinical trial registration: The trial has been registered with ClinicalTrials.gov, number NCT01813435. Graphic abstract: [Figure not available: see fulltext.].

Published
2020
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47. Angiotensin II Infusion Leads to Aortic Dissection in LRP8 Deficient Mice

Author

Jeremy Lagrange, Stefanie Finger, Sabine Kossmann, Venkata Garlapati, Wolfram Ruf, Philip Wenzel, Lagrange, Jeremy, 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), University Medical Center [Mainz], German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), and The Scripps Research Institute [La Jolla, San Diego]

Subjects
Male, 540 Chemistry and allied sciences, [SDV]Life Sciences [q-bio], 610 Medizin, Blood Pressure, Article, 570 Life sciences, lcsh:Chemistry, Mice, low-density lipoprotein receptor-related protein 8, 610 Medical sciences, Cell Adhesion, Animals, Myeloid Cells, RNA, Messenger, lcsh:QH301-705.5, Infusion Pumps, LDL-Receptor Related Proteins, Bone Marrow Transplantation, Microscopy, Video, Angiotensin II, Acetylcholine, [SDV] Life Sciences [q-bio], Vasodilation, Aortic Dissection, Chemotaxis, Leukocyte, Disease Models, Animal, lcsh:Biology (General), lcsh:QD1-999, Gene Expression Regulation, 540 Chemie, Radiation Chimera, cardiovascular system, 570 Biowissenschaften
Abstract

Myeloid cells are crucial for the development of vascular inflammation. Low-density lipoprotein receptor-related protein 8 (LRP8) or Apolipoprotein E receptor 2 (ApoER2), is expressed by macrophages, endothelial cells and platelets and has been implicated in the development of cardiovascular diseases. Our aim was to evaluate the role of LRP8, in particular from immune cells, in the development of vascular inflammation. Methods. LRP8+/+ and LRP8&minus, /&minus, mice (on B6, 129S background) were infused with angiotensin II (AngII, 1 mg/kg/day for 7 to 28 day) using osmotic minipumps. Blood pressure was recorded using tail cuff measurements. Vascular reactivity was assessed in isolated aortic segments. Leukocyte activation and infiltration were assessed by flow cytometry of aortic tissue and intravital videomicroscopy imaging. Histological analysis of aortic sections was conducted using sirius red staining. Results. AngII infusion worsened endothelial-dependent vascular relaxation and immune cells rolling and adherence to the carotid artery in both LRP8+/+ as well as LRP8&minus, mice. However, only LRP8&minus, mice demonstrated a drastically increased mortality rate in response to AngII due to aortic dissection. Bone marrow transplantation revealed that chimeras with LRP8 deficient myeloid cells phenocopied LRP8&minus, mice. Conclusion. AngII-infused LRP8 deficient mice could be a useful animal model to study aortic dissection reflecting the lethality of this disease in humans.

Published
2020
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48. Ipilimumab 10 mg/kg versus ipilimumab 3 mg/kg in patients with unresectable or metastatic melanoma: a randomised, double-blind, multicentre, phase 3 trial

Author

Piotr Rutkowski, Lars Bastholt, Ralf Gutzmer, Claus Garbe, Virginia Ferraresi, Marta Nyakas, Omid Hamid, Joanna Pikiel, Jean-Jacques Grob, Paolo A. Ascierto, Céleste Lebbé, Caroline Robert, Delphine Hennicken, Vanna Chiarion-Sileni, Michael Smylie, Gabriella Liszkay, Florent Grange, Catriona M. McNeil, Luc Thomas, Dirk Schadendorf, Andrzej Mackiewicz, Michele Del Vecchio, Christoph Hoeller, Carmen Loquai, Michele Maio, Inge Marie Svane, Anila Qureshi, Brigitte Dréno, Ana Arance, Laurent Mortier, Istituto Nazionale Tumori Fondazione Pascale [Naples, Italy], Medical Oncology, National Cancer Institute [Milan, Italy], Institut Gustave Roussy ( IGR ), Department of Diagnostics and Cancer Immunology [Poznan, Poland], Greater Poland Cancer Centre [Poznan, Poland]-Poznan Medical University [Poland], Melanoma Oncology Unit [Padova, Italy], Veneto Institute of Oncology IOV-IRCCS [Padua, Italy], Institut d'Investigacions Biomèdiques August Pi I Sunyer [Barcelona, Spain] ( Hospital Clinic ), Immunologie, dermatologie, oncologie, Oncodermatologie, immunologie et cellules souches cutanées ( DIO U976 ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Odense University Hospital [Odense, Denmark], The Angeles Clinic and Research Institute [Los Angeles, CA, USA], Maria Sklodowska-Curie Memorial Cancer Center [Warsaw, Poland], Royal Prince Alfred Hospital ( RPAH - SYDNEY ), Melanoma Institute Australia [Sydney, NSW, Australia], Eberhard Karls University [Tübingen, Germany], University Medical Center [Mainz, Germany], Centre de Recherche en Cancérologie / Nantes - Angers ( CRCNA ), CHU Angers-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Laennec-Centre National de la Recherche Scientifique ( CNRS ) -Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes ( CHU Nantes ), Département de Dermatologie [CH Lyon-Sud, Pierre-Bénite], Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Hôpital de la Timone [CHU - APHM] ( TIMONE ), National Institute of Oncology [Budapest, Hungary], Oslo University Hospital [Oslo, Norway], Medizinische Hochschule Hannover [Hannover, Germany], Wojewodzkie Centrum Oncologii [Gdańsk, Poland], Département de Dermatologie [CHU de Reims], Centre Hospitalier Universitaire de Reims ( CHU Reims ), Medical University of Vienna [Austria], Istituti Fisioterapici Ospitalieri [Rome, Italy], Cross Cancer Institute [Edmonton, AB, Canada], University Hospital [Essen, Germany], Hôspital Claude Huriez [Lille, France], Herlev Hospital [Herlev, Denmark], University of Copenhagen ( KU ), Bristol-Myers Squibb [Princeton, NJ, USA], Istituto Toscano Tumori [Siena, Italy], University Hospital of Siena [Italy], Bristol-Myers Squibb., Institut Gustave Roussy (IGR), Institut d'Investigacions Biomèdiques August Pi I Sunyer [Barcelona, Spain] (Hospital Clinic ), Oncodermatologie, immunologie et cellules souches cutanées (IDO (U976 / UMR_S 976)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cedars-Sinai Medical Center, Royal Prince Alfred Hospital (RPAH - SYDNEY), Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Hôpital de la Timone [CHU - APHM] (TIMONE), Oslo University Hospital [Oslo], Centre Hospitalier Universitaire de Reims (CHU Reims), Medizinische Universität Wien = Medical University of Vienna, Hôpital Claude Huriez [Lille], CHU Lille, Herlev and Gentofte Hospital, Bristol-Myers Squibb [Princeton], and Bernardo, Elizabeth

Subjects
Male, 0301 basic medicine, Medizin, Gastroenterology, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Clinical endpoint, Melanoma, education.field_of_study, Hazard ratio, Antibodies, Monoclonal, Alanine Transaminase, Middle Aged, Colitis, Intention to Treat Analysis, 3. Good health, Survival Rate, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Female, medicine.drug, Diarrhea, medicine.medical_specialty, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Antineoplastic Agents, Ipilimumab, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Double-Blind Method, Internal medicine, Journal Article, medicine, Humans, Hypophysitis, Adverse effect, education, Survival rate, Aged, Intention-to-treat analysis, business.industry, Surgery, 030104 developmental biology, business, Follow-Up Studies
Abstract

BACKGROUND: A phase 2 trial suggested increased overall survival and increased incidence of treatment-related grade 3-4 adverse events with ipilimumab 10 mg/kg compared with ipilimumab 3 mg/kg in patients with advanced melanoma. We report a phase 3 trial comparing the benefit-risk profile of ipilimumab 10 mg/kg versus 3 mg/kg.METHODS: This randomised, double-blind, multicentre, phase 3 trial was done in 87 centres in 21 countries worldwide. Patients with untreated or previously treated unresectable stage III or IV melanoma, without previous treatment with BRAF inhibitors or immune checkpoint inhibitors, were randomly assigned (1:1) with an interactive voice response system by the permuted block method using block size 4 to ipilimumab 10 mg/kg or 3 mg/kg, administered by intravenous infusion for 90 min every 3 weeks for four doses. Patients were stratified by metastasis stage, previous treatment for metastatic melanoma, and Eastern Cooperative Oncology Group performance status. The patients, investigators, and site staff were masked to treatment assignment. The primary endpoint was overall survival in the intention-to-treat population and safety was assessed in all patients who received at least one dose of study treatment. This study is completed and was registered with ClinicalTrials.gov, number NCT01515189.FINDINGS: Between Feb 29, and July 9, 2012, 727 patients were enrolled and randomly assigned to ipilimumab 10 mg/kg (365 patients; 364 treated) or ipilimumab 3 mg/kg (362 patients; all treated). Median follow-up was 14·5 months (IQR 4·6-42·3) for the ipilimumab 10 mg/kg group and 11·2 months (4·9-29·4) for the ipilimumab 3 mg/kg group. Median overall survival was 15·7 months (95% CI 11·6-17·8) for ipilimumab 10 mg/kg compared with 11·5 months (9·9-13·3) for ipilimumab 3 mg/kg (hazard ratio 0·84, 95% CI 0·70-0·99; p=0·04). The most common grade 3-4 treatment-related adverse events were diarrhoea (37 [10%] of 364 patients in the 10 mg/kg group vs 21 [6%] of 362 patients in the 3 mg/kg group), colitis (19 [5%] vs nine [2%]), increased alanine aminotransferase (12 [3%] vs two [1%]), and hypophysitis (ten [3%] vs seven [2%]). Treatment-related serious adverse events were reported in 133 (37%) patients in the 10 mg/kg group and 66 (18%) patients in the 3 mg/kg group; four (1%) versus two (INTERPRETATION: In patients with advanced melanoma, ipilimumab 10 mg/kg resulted in significantly longer overall survival than did ipilimumab 3 mg/kg, but with increased treatment-related adverse events. Although the treatment landscape for advanced melanoma has changed since this study was initiated, the clinical use of ipilimumab in refractory patients with unmet medical needs could warrant further assessment.FUNDING: Bristol-Myers Squibb.

Published
2017
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49. Neochord anterior leaflet treatment to facilitate transcatheter mitral valve replacement with 3D real-time echocardiography

Author

Ralph Stephan von Bardeleben, Andres Beiras-Fernandez, T Ruf, Thomas Münzel, Felix Kreidel, Jean-François Obadia, CarMeN, laboratoire, University Medical Center [Mainz], Services de Pneumologie, Exploration Fonctionnelle Respiratoire et Cardiologie (Hôpital Louis Pradel), and Hospices Civils de Lyon (HCL)

Subjects
medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Echocardiography, Three-Dimensional, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Medicine, Humans, AcademicSubjects/MED00200, ComputingMilieux_MISCELLANEOUS, Heart Valve Prosthesis Implantation, Anterior leaflet, business.industry, Mitral valve replacement, Mitral Valve Insufficiency, 3. Good health, Surgery, [SDV] Life Sciences [q-bio], Treatment Outcome, Mitral valve replacement surgery, Mitral Valve, Cardiovascular Flashlight, Cardiology and Cardiovascular Medicine, business, Echocardiography, Transesophageal
Abstract

International audience; No abstract available

Published
2020
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50. Pimasertib Versus Dacarbazine in Patients With Unresectable NRAS-Mutated Cutaneous Melanoma: Phase II, Randomized, Controlled Trial with Crossover

Author

Céleste Lebbé, Armin Schueler, Richard Isaacs, Giorgio Massimini, Willem Kruit, Brigitte Dreno, Virginia Ferraresi, Caroline Robert, Luc Thomas, Enrique Espinosa, Carmen Loquai, Paul Vasey, Joseph Kerger, Bernard Guillot, Jean-Jacques Grob, Robert M. Conry, Caroline Dutriaux, Claus Garbe, Filippo de Braud, Thierry Lesimple, Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Service de Dermatologie [AP-HP Hôpital Saint-Louis], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CIC Saint Louis (CIC-1427), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service de dermatologie Hôpital Saint-André Bordeaux, CHU Bordeaux [Bordeaux], Centre Eugène Marquis (CRLCC), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), IRCCS Istituto Nazionale dei Tumori [Milano], Università degli Studi di Milano [Milano] (UNIMI), Universitätsklinikum Tübingen - University Hospital of Tübingen, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Service de dermatologie, vénéreologie et cancérologie cutanée [Hôpital de la Timone - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), University Medical Center [Mainz], IFO - Istituto Nazionale Tumori Regina Elena [Roma] (IRE), Institut Gustave Roussy (IGR), Oncologie dermatologique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), University of Alabama at Birmingham [ Birmingham] (UAB), Palmerston North Hospital [Palmerston North], Hospital Universitario La Paz, Merck [Darmstadt], Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Medical Oncology, Herrada, Anthony, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Università degli Studi di Milano = University of Milan (UNIMI), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), and Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)

Subjects
Cancer Research, Gastroenterology, pimasertib, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Clinical endpoint, 030212 general & internal medicine, Malignant melanoma, Hazard ratio, Progression-free survival, Sciences bio-médicales et agricoles, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, Dacarbazine, Oncology, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, 030220 oncology & carcinogenesis, medicine.symptom, Pimasertib, medicine.drug, Quality of life, medicine.medical_specialty, Nausea, malignant melanoma, dacarbazine, [SDV.CAN]Life Sciences [q-bio]/Cancer, N-(2 3-dihydroxypropyl)-1-((2-fluoro-4-iodophenyl)amino)isonicotinamide, Neutropenia, N-(2,3-dihydroxypropyl)-1-((2-fluoro-4-iodophenyl)amino)isonicotinamide, lcsh:RC254-282, Article, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Adverse effect, business.industry, [SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology, medicine.disease, adverse events, Cancérologie, quality of life, Adverse events, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, business, progression-free survival, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract

This study investigated the efficacy and safety of pimasertib (MEK1/MEK2 inhibitor) versus dacarbazine (DTIC) in patients with untreated NRAS-mutated melanoma. Phase II, multicenter, open-label trial. Patients with unresectable, stage IIIc/IVM1 NRAS-mutated cutaneous melanoma were randomized 2:1 to pimasertib (60 mg, oral twice-daily) or DTIC (1000 mg/m2, intravenously) on Day 1 of each 21-day cycle. Patients progressing on DTIC could crossover to pimasertib. Primary endpoint: investigator-assessed progression-free survival (PFS), secondary endpoints: overall survival (OS), objective response rate (ORR), quality of life (QoL), and safety. Overall, 194 patients were randomized (pimasertib n = 130, DTIC n = 64), and 191 received treatment (pimasertib n = 130, DTIC n = 61). PFS was significantly improved with pimasertib versus DTIC (median 13 versus 7 weeks, respectively, hazard ratio (HR) 0.59, 95% confidence interval (CI) 0.42&ndash, 0.83, p = 0.0022). ORR was improved with pimasertib (odds ratio 2.24, 95% CI 1.00&ndash, 4.98, p = 0.0453). OS was similar between treatments (median 9 versus 11 months, respectively, HR 0.89, 95% CI 0.61&ndash, 1.30), 64% of patients receiving DTIC crossed over to pimasertib. Serious adverse events (AEs) were more frequent for pimasertib (57%) than DTIC (20%). The most common treatment-emergent AEs were diarrhea (82%) and blood creatine phosphokinase (CPK) increase (68%) for pimasertib, and nausea (41%) and fatigue (38%) for DTIC. Most frequent grade &ge, 3 AEs were CPK increase (34%) for pimasertib and neutropenia (15%) for DTIC. Mean QoL scores (baseline and last assessment) were similar between treatments. Pimasertib has activity in NRAS-mutated cutaneous melanoma and a safety profile consistent with known toxicities of MEK inhibitors. Trial registration: ClinicalTrials.gov, NCT01693068

Published
2020
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