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1. THIRST Alert Trial (THIRST)

Author: University College London Hospitals (UCLH) NHS Foundation Trust and National Institute for Health and Care Research (NIHR) UCLH Biomedical Research Centre
Published: 2023

2. Relationship between paramagnetic rim lesions and slowly expanding lesions in multiple sclerosis

Author: Calvi, Alberto, Clarke, Margareta A., Prados, Ferran, Chard, Declan, Ciccarelli, Olga, Alberich, Manel, Pareto, Deborah, Rodríguez Barranco, Marta, Sastre-Garriga, Jaume, Tur, Carmen, Rovira, Alex, Barkhof, Frederik, Universitat Autònoma de Barcelona, Institut Català de la Salut, [Calvi A] Queen Square MS Centre, Department of Neuroinflammation, Institute of Neurology, Faculty of Brain Sciences, University College London (UCL), London, UK. [Clarke MA, Alberich M, Pareto D, Rovira A] Secció de Neuroradiologia, Servei de Radiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Prados F, Chard D, Ciccarelli O] Queen Square MS Centre, Department of Neuroinflammation, Institute of Neurology, Faculty of Brain Sciences, University College London (UCL), London, UK. Biomedical Research Centre, National Institute for Health Research (NIHR) and University College London Hospitals (UCLH), London, UK. [Rodríguez Barranco M, Sastre-Garriga J] Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (CEMCAT), Barcelona, Spain. [Tur C] Queen Square MS Centre, Department of Neuroinflammation, Institute of Neurology, Faculty of Brain Sciences, University College London (UCL), London, UK. Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (CEMCAT), Barcelona, Spain. [Barkhof F] Queen Square MS Centre, Department of Neuroinflammation, Institute of Neurology, Faculty of Brain Sciences, University College London (UCL), London, UK/Centre for Medical Image Computing (CMIC), Department of Medical Physics and Biomedical Engineering, University College London, London, UK Biomedical Research Centre, National Institute for Health Research (NIHR) and University College London Hospitals (UCLH), London, UK/Radiology & Nuclear medicine, VU University Medical Centre, Amsterdam, The Netherlands, Vall d'Hebron Barcelona Hospital Campus, Radiology and nuclear medicine, Amsterdam Neuroscience - Brain Imaging, Amsterdam Neuroscience - Neuroinfection & -inflammation, CCA - Cancer Treatment and quality of life, and CCA - Imaging and biomarkers
Subjects: Multiple sclerosis, Volumetric MRI, Neurology, Chronic active lesions, Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Imaging::Tomography::Magnetic Resonance Imaging [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], enfermedades del sistema nervioso::enfermedades autoinmunitarias del sistema nervioso::enfermedades autoinmunes desmielinizantes del SNC::esclerosis múltiple [ENFERMEDADES], Slowly expanding lesions (SELs), Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis [DISEASES], Susceptibility-weighted imaging (SWI), diagnóstico::técnicas y procedimientos diagnósticos::diagnóstico por imagen::tomografía::imagen por resonancia magnética [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Neurology (clinical), Paramagnetic rim lesions (PRLs), Esclerosi múltiple - Imatgeria per ressonància magnètica
Abstract: Background: Magnetic resonance imaging (MRI) markers for chronic active lesions in MS include slowly expanding lesions (SELs) and paramagnetic rim lesions (PRLs). Objectives: To identify the relationship between SELs and PRLs in MS, and their association with disability. Methods: 61 people with MS (pwMS) followed retrospectively with MRI including baseline susceptibility-weighted imaging, and longitudinal T1 and T2-weighted scans. SELs were computed using deformation field maps; PRLs were visually identified. Mixed-effects models assessed differences in Expanded Disability Status Scale (EDSS) score changes between the group defined by the presence of SELs and or PRLs. Results: The median follow-up time was 3.2 years. At baseline, out of 1492 lesions, 616 were classified as SELs, and 80 as PRLs. 92% of patients had ⩾ 1 SEL, 56% had ⩾ 1 PRL, while both were found in 51%. SELs compared to non-SELs were more likely to also be PRLs (7% vs. 4%, p = 0.027). PRL counts positively correlated with SEL counts (ρ= 0.28, p = 0.03). SEL + PRL + patients had greater increases in EDSS over time (beta = 0.15/year, 95% confidence interval (0.04, 0.27), p = 0.009) than SEL+PRL-patients. Conclusion: SELs are more numerous than PRLs in pwMS. Compared with either SELs or PRLs found in isolation, their joint occurrence was associated with greater clinical progression.
Published: 2022
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3. Comparative study of preterm infants fed new and existing human milk fortifiers showed favourable markers of gastrointestinal status

Author: Jacques Rigo, M. Radke, Fabio Mosca, Jean Michel Hascoët, Jean Charles Picaud, Umberto Simeoni, Nicholas P. Hays, Mickaël Hartweg, Elie Saliba, Johannes Spalinger, Claude Billeaud, Bernard Guillois, Amandine Rubio, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), AZTI-Tecnalia (Marine Research Division), AZTI-Tecnalia, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Department of Neonatology [London], Institute for Women's Health [London], University College London Hospitals (UCLH)-University College London Hospitals (UCLH), Maternité Régionale Adolphe Pinard [Nancy], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Centre Hospitalier Universitaire [Grenoble] (CHU), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Georges Clémenceau, Nestlé Product Technology Center, CHU de Bordeaux Pellegrin [Bordeaux], and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)
Subjects: [SDV]Life Sciences [q-bio], Weight Gain, calprotectin, Enteral administration, Gastroenterology, Belgium, Biomarkers, Food, Fortified, France, Germany, Humans, Infant, Infant, Newborn, Infant, Premature, Italy, Milk, Human, Switzerland, alpha-1 antitrypsin, elastase-1, low birthweight infant, prematurity, 0302 clinical medicine, fluids and secretions, 030212 general & internal medicine, alpha‐1 antitrypsin, High concentration, Regular Article, General Medicine, Gut inflammation, medicine.medical_specialty, 03 medical and health sciences, low birth weight infant, 030225 pediatrics, Internal medicine, Intensive care, elastase‐1, medicine, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Group study, business.industry, Significant difference, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Faecal calprotectin, Pediatrics, Perinatology and Child Health, Neonatology, Calprotectin, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Regular Articles
Abstract: International audience; Aim: This study examined the influence of different human milk fortifiers on biomarkers of gastrointestinal immaturity and inflammation in preterm infants.Methods: We report secondary outcomes from a controlled, double‐blind, randomised, parallel group study conducted from 2011 to 2014 in neonatal intensive care units at 11 metropolitan hospitals in France, Belgium, Germany, Switzerland and Italy. Preterm infants born at up to 32 weeks or weighing up to 1500 g were randomised to a new powdered human milk fortifier (n = 77) or a control fortifier (n = 76) for a minimum of 21 days. We analysed faecal markers of gut inflammation, namely alpha‐1 antitrypsin and calprotectin, and maturity, namely elastase‐1.Results: Faecal alpha‐1 antitrypsin was slightly lower in the new than control fortifier group after 21 days of full enteral feeding, with a geometric mean and standard deviation of 1.52 ± 1.32 vs 1.82 ± 1.44 mg/g stools (P = .01). There was no significant difference in faecal calprotectin (median [Q1‐Q3] of 296 [136‐565] μg/g stools in both groups combined at study day 21). Faecal elastase‐1 was lower in the new fortifier than control fortifier group (202.5 ± 1.6 vs 257.7 ± 1.5 μg/g stools, P = .016).Conclusion: Mean values for each parameter were within the ranges in healthy term infants, indicating favourable markers of gastrointestinal status in both groups. In addition, for faecal calprotectin, the relatively high concentration observed in preterm infants fed fortified human milk suggests that the threshold level for detecting necrotising enterocolitis should be revised.
Published: 2019
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4. Best practices for the management of local-regional recurrent chordoma: a position paper by the chordoma global consensus group

Author: Vittoria Colia, Bernd Kasper, R. Imai, Michael Baumann, Stéphanie Bolle, R. Capanna, Riccardo Casadei, Paolo G. Casali, Claire Alapetite, P. A. Gardner, C. L. A. Vleggeert-Lankamp, C. Heery, Elena Tamborini, Anant Desai, Stefano Radaelli, Alessandro Gronchi, Nadia Hindi, Akira Kawai, Daniel Vanel, C. Sen, Francesco Doglietto, Nicolas Penel, Ziya L. Gokaslan, S. Froelich, Katherine Anne Thornton, Carlo Morosi, Hans Gelderblom, Francis J. Hornicek, O. J. Norum, M. Uhl, Palma Dileo, Sandip Pravin Patel, Piero Fossati, J. Martin Broto, Peter Hohenberger, Rick L. Haas, Andreas Leithner, Toru Akiyama, F. Ricchini, Robin L. Jones, Valter Torri, Josh Sommer, Peter Pal Varga, Y. Yamada, Per-Ulf Tunn, J.-Y. Blay, Augusto Caraceni, Piotr Rutkowski, Jürgen Debus, Lee Jeys, Adrienne M. Flanagan, Diego Mazzatenta, I. Logowska, Marco Krengli, Damien C. Weber, Thomas F. DeLaney, Susanne Scheipl, P. Picci, Beate Timmermann, Piero Nicolai, S. Pilotti, P. Bruzzi, Silvia Stacchiotti, Stefano Boriani, S. Dijkstra, Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], European Institute of Oncology [Milan] (ESMO), Saitama University, Institut Curie [Paris], University of Dresden Medical School, Centre Léon Bérard [Lyon], Institut Gustave Roussy (IGR), University of Pisa - Università di Pisa, University Medical Center Heidelberg, Massachusetts General Hospital [Boston], Queen Elizabeth Hospital, University College London Hospitals (UCLH), Universiteit Leiden [Leiden], University of Brescia, Cancer Research UK London Research Institute, Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Providence University, Netherlands Cancer Institute (NKI), Antoni van Leeuwenhoek Hospital, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Hospital Universitario Virgen del Rocío [Sevilla], University of Heidelberg, Medical Faculty, Harvard Medical School [Boston] (HMS), Chiba University Hospital, Queens Elizabeth Hospital [Birmingham], Royal Marsden NHS Foundation Trust, National Cancer Center Research Institute [Tokyo], Università del Piemonte Orientale - Dipartimento DISIT Italy, Medical University Graz, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), MD Anderson Cancer Center [Houston], The University of Texas Health Science Center at Houston (UTHealth), Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), University Hospital Graz, New York University Langone Medical Center (NYU Langone Medical Center), NYU System (NYU), University of Duisbourg-Essen, Helios Klinikum [Erfurt], Memorial Sloane Kettering Cancer Center [New York], SwissFEL, Paul Scherrer Institut, Leiden University Medical Center (LUMC), Universiteit Leiden, CHU Lille, Université de Lille, METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694, European Institute of Oncology [Milan] [ESMO], Institut Gustave Roussy [IGR], University College London Hospitals [UCLH], Netherlands Cancer Institute [NKI], National Cancer Institute [Bethesda] [NCI-NIH], Harvard Medical School [Boston] [HMS], Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology [MCMCC], Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS], New York University Langone Medical Center [NYU Langone Medical Center], Leiden University Medical Center [LUMC], Stacchiotti, S., Gronchi, A., Fossati, P., Akiyama, T., Alapetite, C., Baumann, M., Blay, J. Y., Bolle, S., Boriani, S., Bruzzi, P., Capanna, R., Caraceni, A., Casadei, R., Colia, V., Debus, J., Delaney, T., Desai, A., Dileo, P., Dijkstra, S., Doglietto, F., Flanagan, A., Froelich, S., Gardner, P. A., Gelderblom, H., Gokaslan, Z. L., Haas, R., Heery, C., Hindi, N., Hohenberger, P., Hornicek, F., Imai, R., Jeys, L., Jones, R. L., Kasper, B., Kawai, A., Krengli, M., Leithner, A., Logowska, I., Martin Broto, J., Mazzatenta, D., Morosi, C., Nicolai, P., Norum, O. J., Patel, S., Penel, N., Picci, P., Pilotti, S., Radaelli, S., Ricchini, F., Rutkowski, P., Scheipl, S., Sen, C., Tamborini, E., Thornton, K. A., B., Timmermann, Torri, V., Tunn, P. U., Uhl, M., Yamada, Y., Weber, D. C., Vanel, D., Varga, P. P., Vleggeert-Lankamp, C. L. A., Casali, P. G., and Sommer, J.
Subjects: sarcoma, [SDV]Life Sciences [q-bio], Medizin, chemotherapy, Patient advocacy, surgery, 0302 clinical medicine, Neoplasm Recurrence, Medicine, chordoma, relapse, radiotherapy, Relapse, Sarcoma, Hematology, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Practice Guidelines as Topic, chordoma, consensus, recurrence, Sacral Chordoma, musculoskeletal diseases, medicine.medical_specialty, recurrence, Best practice, MEDLINE, Reviews, 610 Medicine & health, 03 medical and health sciences, Chordoma, Humans, Chemotherapy, Medical physics, Radiotherapy, business.industry, medicine.disease, Cervical spine, consensus, Family medicine, Position paper, Surgery, Neoplasm Recurrence, Local, business, 030217 neurology & neurosurgery
Abstract: Chordomas are rare, malignant bone tumors of the skull-base and axial skeleton. Until recently, there was no consensus among experts regarding appropriate clinical management of chordoma, resulting in inconsistent care and suboptimal outcomes for many patients. To address this shortcoming, the European Society of Medical Oncology (ESMO) and the Chordoma Foundation, the global chordoma patient advocacy group, convened a multi-disciplinary group of chordoma specialists to define by consensus evidence-based best practices for the optimal approach to chordoma. In January 2015, the first recommendations of this group were published, covering the management of primary and metastatic chordomas. Additional evidence and further discussion were needed to develop recommendations about the management of local-regional failures. Thus, ESMO and CF convened a second consensus group meeting in November 2015 to address the treatment of locally relapsed chordoma. This meeting involved over 60 specialists from Europe, the United States and Japan with expertise in treatment of patients with chordoma. The consensus achieved during that meeting is the subject of the present publication and complements the recommendations of the first position paper.
Published: 2017
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5. The Effect of Dutasteride on Magnetic Resonance Imaging Defined Prostate Cancer: MAPPED-A Randomized, Placebo Controlled, Double-Blind Clinical Trial

Author: Adebiyi Damola, Mathias Winkler, Manit Arya, Mark Emberton, Nicola L. Robertson, Hashim U. Ahmed, Gareth Ambler, Charles Jameson, Ramiro Castro, Fatima Jichi, Ashley J Ridout, Caroline M. Moore, Simon Bott, Neil McCartan, Clare Allen, Alex Kirkham, Anita Mitra, Francesco Giganti, Alex Freeman, Brandon Whitcher, Giulio Gambarota, Division of Surgery and Interventional Science [London, UK], University College of London [London] (UCL), Department of Urology [London, UK] ( King's College Hospital NHS Foundation Trust), King's College Hospital (KCH)-University College of London [London] (UCL), Biostatistics Group [London, UK], University College of London [London] (UCL)-University College London Hospitals (UCLH)-University College London Research Support Centre [UK], Department of Radiology [London, UK], University College London Hospitals (UCLH), Department of Urology [Surrey, UK], Frimley Park Hospital [Surrey, UK], Department of Urology [London, UK] (Charing Cross Hospital), Imperial College NHS Trust [London, UK] -Charing Cross Hospital [London, UK], Department of Clinical Oncology [London, UK], Department of Pathology [London, UK], GlaxoSmithKline Research and Development [Philadelphia, USA], 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), Department of Mathematics [Imperial College London], Imperial College London, Klarismo [London, UK], University College of London [London] (UCL)-University College London Hospitals (UCLH), Imperial College London-Charing Cross Hospital [London, UK], Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent
Subjects: Male, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Biopsy, 030232 urology & nephrology, Placebo-controlled study, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, chemistry.chemical_compound, Prostate cancer, 0302 clinical medicine, 5-alpha Reductase Inhibitors, TARGETED BIOPSY, RISK, dutasteride, medicine.diagnostic_test, INHIBITOR, Urology & Nephrology, Middle Aged, Magnetic Resonance Imaging, 3. Good health, Tumor Burden, Prostate-specific antigen, 030220 oncology & carcinogenesis, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Life Sciences & Biomedicine, MRI, Adult, medicine.medical_specialty, Urology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Placebo, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Double-Blind Method, Lower urinary tract symptoms, medicine, Humans, Aged, watchful waiting, Gynecology, Science & Technology, business.industry, Prostatic Neoplasms, Magnetic resonance imaging, 1103 Clinical Sciences, medicine.disease, Dutasteride, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, ACTIVE SURVEILLANCE, Clinical trial, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, chemistry, VOLUME, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, business
Abstract: International audience; PURPOSE: Dutasteride, which is licensed for symptomatic benign prostatic hyperplasia, has been associated with a lower progression rate of low risk prostate cancer. We evaluated the effect of dutasteride on prostate cancer volume as assessed by T2-weighted magnetic resonance imaging.MATERIALS AND METHODS: In this randomized, double-blind, placebo controlled trial, men with biopsy proven, low-intermediate risk prostate cancer (up to Gleason 3 + 4 and PSA up to 15 ng/ml) who had visible lesion of 0.2 ml or greater on T2-weighted magnetic resonance imaging sequences were randomized to daily dutasteride 0.5 mg or placebo for 6 months. Lesion volume was assessed at baseline, and 3 and 6 months with image guided biopsy to the lesion at study exit. The primary end point was the percent reduction in lesion volume over 6 months. This trial was registered with the European Clinical Trials register (EudraCT 2009-102405-18).RESULTS: A total of 42 men were recruited between June 2010 and January 2012. In the dutasteride group, the average volumes at baseline and 6 months were 0.55 and 0.38 ml, respectively and the average reduction was 36%. In the placebo group, the average volumes at baseline and 6 months were 0.65 and 0.76 ml, respectively, and the average reduction was -12%. The difference in percent reductions between the groups was 48% (95% CI 27.4-68.3, p
Published: 2017
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6. Developing a knowledge base to support the annotation of ultrasound images of ectopic pregnancy

Author: Dhombres, F., Maurice, P., Friszer, S., Guilbaud, L., Lelong, N., Khoshnood, B., Jean Charlet, Perrot, N., Jauniaux, E., Jurkovic, D., Jm Jouannic, Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé (LIMICS), Université Paris 13 (UP13)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Université Paris Descartes - Paris 5 (UPD5)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Echographie [Paris], Centre d’Imagerie Médicale Pyramides [Paris], Department of Obstetrics and Gynaecology [UCL - London, UK], University College of London [London] (UCL)-Institute for Women's Health [London, UK], Department of Obstetrics and Gynaecology [UCLH - London, UK], Gynaecology Diagnostic and Outpatient Treatment Unit [UCLH - London, UK], University College London Hospitals (UCLH)-University College London Hospitals (UCLH), The development of the web-application was founded by the SATT-Lutech for the Pierre and Marie Curie University, Paris, France., Charlet, Jean, Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé ( LIMICS ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris 13 ( UP13 ), Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique ( CRESS - U1153 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité ( CRESS (U1153 / UMR_A 1125) ), Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA ), University College of London [London] ( UCL ) -Institute for Women's Health [London, UK], University College London Hospitals ( UCLH ) -University College London Hospitals ( UCLH ), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), and BMC, BMC
Subjects: [ SDV ] Life Sciences [q-bio], Ectopic pregnancy, Research, [SDV]Life Sciences [q-bio], Application ontology, Pregnancy, Ectopic, [SDV] Life Sciences [q-bio], Knowledge base, Biological Ontologies, Pregnancy, Data Mining, Humans, Female, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Ultrasonography, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM]
Abstract: International audience; AbstractBackgroundEctopic pregnancy is a frequent early complication of pregnancy associated with significant rates of morbidly and mortality. The positive diagnosis of this condition is established through transvaginal ultrasound scanning. The timing of diagnosis depends on the operator expertise in identifying the signs of ectopic pregnancy, which varies dramatically among medical staff with heterogeneous training. Developing decision support systems in this context is expected to improve the identification of these signs and subsequently improve the quality of care. In this article, we present a new knowledge base for ectopic pregnancy, and we demonstrate its use on the annotation of clinical images.ResultsThe knowledge base is supported by an application ontology, which provides the taxonomy, the vocabulary and definitions for 24 types and 81 signs of ectopic pregnancy, 484 anatomical structures and 32 technical elements for image acquisition. The knowledge base provides a sign-centric model of the domain, with the relations of signs to ectopic pregnancy types, anatomical structures and the technical elements. The evaluation of the ontology and knowledge base demonstrated a positive feedback from a panel of 17 medical users. Leveraging these semantic resources, we developed an application for the annotation of ultrasound images. Using this application, 6 operators achieved a precision of 0.83 for the identification of signs in 208 ultrasound images corresponding to 35 clinical cases of ectopic pregnancy.ConclusionsWe developed a new ectopic pregnancy knowledge base for the annotation of ultrasound images. The use of this knowledge base for the annotation of ultrasound images of ectopic pregnancy showed promising results from the perspective of clinical decision support system development. Other gynecological disorders and fetal anomalies may benefit from our approach.
Published: 2016
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7. Brain Perfusion Imaging in Neonates: An Overview

Author: F. Le Jeune, Maïa Proisy, Subhabrata Mitra, C. Uria-Avellana, Nicola J. Robertson, Magdalena Sokolska, Jean-Christophe Ferré, CHU Pontchaillou [Rennes], Vision, Action et Gestion d'informations en Santé (VisAGeS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE (IRISA-D5), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), CentraleSupélec-Télécom Bretagne-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Télécom Bretagne-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Department of Neonatology [London], Institute for Women's Health [London], University College London Hospitals (UCLH)-University College London Hospitals (UCLH), Institute of Neurology [London], University College of London [London] (UCL), Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), and Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR)
Subjects: business.industry, Perfusion scanning, Brain damage, medicine.disease, Pediatrics, Hypoxic Ischemic Encephalopathy, 3. Good health, 030218 nuclear medicine & medical imaging, Perinatal asphyxia, 03 medical and health sciences, 0302 clinical medicine, Intraventricular hemorrhage, Cerebral blood flow, Neuroimaging, Medicine, Radiology, Nuclear Medicine and imaging, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), medicine.symptom, business, Neuroscience, Perfusion, 030217 neurology & neurosurgery, ComputingMilieux_MISCELLANEOUS
Abstract: The development of cognitive function in children has been related to a regional metabolic increase and an increase in regional brain perfusion. Moreover, brain perfusion plays an important role in the pathogenesis of brain damage in high-risk neonates, both preterm and full-term asphyxiated infants. In this article, we will review and discuss several existing imaging techniques for assessing neonatal brain perfusion.
Published: 2016
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8. Operationalizing the centiloid scale for [18 F]florbetapir PET studies on PET/MRI

Author: Coath, William, Modat, Marc, Cardoso, M. Jorge, Markiewicz, Pawel, Lane, Christopher, Parker, Thomas, Keshavan, Ashvini, Buchanan, Sarah, Keuss, Sarah, Harris, Matthew, Burgos, Ninon, Dickson, John, Barnes, Anna, Thomas, David, Beasley, Daniel, Malone, Ian, Wong, Andrew, Erlandsson, Kjell, Thomas, Benjamin, Schöll, Michael, Ourselin, Sebastien, Richards, Marcus, Fox, Nick, Schott, Jonathan, Cash, David, UCL Institute of Neurology, Queen Square [London], King‘s College London, University College of London [London] (UCL), Algorithms, models and methods for images and signals of the human brain (ARAMIS), Sorbonne Université (SU)-Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and University College London Hospitals (UCLH)
Subjects: [INFO.INFO-IM]Computer Science [cs]/Medical Imaging
Abstract: International audience; INTRODUCTIONThe Centiloid scale aims to harmonize amyloid beta (Aβ) positron emission tomography (PET) measures across different analysis methods. As Centiloids were created using PET/computerized tomography (CT) data and are influenced by scanner differences, we investigated the Centiloid transformation with data from Insight 46 acquired with PET/magnetic resonanceimaging (MRI).METHODSWe transformed standardized uptake value ratios (SUVRs) from 432 florbetapir PET/MRI scans processed using whole cerebellum (WC) and white matter (WM) references, with and without partial volume correction. Gaussian-mixture-modelling–derived cutpoints for Aβ PET positivity were converted.RESULTSThe Centiloid cutpoint was 14.2 for WC SUVRs. The relationship between WM and WC uptake differed between the calibration and testing datasets, producing implausibly low WM-based Centiloids. Linear adjustment produced a WM-based cutpoint of 18.1.DISCUSSIONTransformation of PET/MRI florbetapir data to Centiloids is valid. However, further understanding of the effects of acquisition or biological factors on the transformation using a WM reference is needed.HIGHLIGHTS Centiloid conversion of amyloid beta positron emission tomography (PET) data aims to standardize results. Centiloid values can be influenced by differences in acquisition. We converted florbetapir PET/magnetic resonance imaging data from a large birth cohort. Whole cerebellum referenced values could be reliably transformed to Centiloids. White matter referenced values may be less generalizable between datasets.
Published: 2023
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9. Description of the SAGhE Cohort: A Large European Study of Mortality and Cancer Incidence Risks after Childhood Treatment with Recombinant Growth Hormone

Author: Swerdlow , Anthony, Cooke , Rosie, Albertsson-Wikland , Kerstin, Borgström , Birgit, Butler , Gary, Cianfarani , Stefano, Clayton , Peter, Coste , Joël, Deodati , Annalisa, Ecosse , Emmanuel, Gausche , Ruth, Giacomozzi , Claudio, Kiess , Wieland, Hokken-Koelega , Anita, Kuehni , Claudia, Landier , Fabienne, Maes , Marc, Mullis , Primus-E, Pfaffle , Roland, Sävendahl , Lars, Sommer , Grit, Thomas , Muriel, Tollerfield , Sally, Zandwijken , Gladys, Carel , Jean-Claude, UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, UCL - (SLuc) Unité d'endocrinologie pédiatrique, Institute of Cancer Research - ICR [London, U.K.], Sahlgrenska Academy at University of Gothenburg [Göteborg], Karolinska Institutet [Stockholm], Institute of Child Health [London], University College of London [London] (UCL), University College London Hospitals (UCLH), IRCCS Ospedale Pediatrico Bambino Gesù [Roma], Royal Manchester Children's Hospital, University of Manchester [Manchester], Unité d’Epidémiologie et de Biostatistiques [APHP Cochin-Broca-Hôtel Dieu], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Universität Leipzig [Leipzig], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Sophia Children's Hospital, Institute of Social and Preventive Medicine [Bern] (ISPM), Universität Bern [Bern], Centre de Référence des Maladies Endocriniennes Rares de la Croissance [APHP Robert Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Service d'endocrinologie diabétologie pédiatrique [CHU Debré], AP-HP Hôpital universitaire Robert-Debré [Paris], Université Paris Diderot - Paris 7 (UPD7), Centre d'Investigation Clinique - Epidemiologie Clinique/essais Cliniques Hopital Robert Debre, Institut National de la Santé et de la Recherche Médicale (INSERM), Cliniques universitaires St Luc [Bruxelles], Inselspital Bern, Belgian Study Group for Pediatric Endocrinology (BSGPE), Universitair Ziekenhuis Brussel, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), University College of London [London] ( UCL ), University College London Hospitals ( UCLH ), Maladies chroniques, santé perçue, et processus d'adaptation. Approches épidémiologiques et psychologiques. ( APEMAC - EA 4360 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Erasmus Medical Center / Dutch Growth Research Foundation, Erasmus University Medical Center [Rotterdam], Institute of Social and Preventive Medicine [Bern] ( ISPM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 ( UPD7 ), Université Paris Diderot - Paris 7 ( UPD7 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), Belgian Study Group for Pediatric Endocrinology ( BSGPE ), and Pediatrics
Subjects: Male, MESH : Risk, MESH : Child, Preschool, Cohort Studies, MESH: Cause of Death, MESH: Recombinant Proteins, MESH : Child, Cause of Death, Neoplasms, MESH: Child, MESH: Human Growth Hormone, MESH : Female, MESH: Neoplasms, MESH: Incidence, Child, MESH: Cohort Studies, Growth Disorders, Cancer, MESH: Risk, Human Growth Hormone, Incidence, MESH: Infant, Newborn, Cohort, MESH : Infant, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Follow-Up Studies, MESH: Growth Disorders, MESH: Infant, MESH : Incidence, Recombinant Proteins, Europe, MESH: Young Adult, Child, Preschool, Female, Risk, Adolescent, MESH : Recombinant Proteins, MESH : Male, MESH : Europe, MESH : Young Adult, MESH : Cohort Studies, 610 Medicine & health, MESH : Infant, Newborn, Young Adult, SDG 3 - Good Health and Well-being, 360 Social problems & social services, MESH : Adolescent, Humans, MESH : Growth Disorders, MESH : Human Growth Hormone, Mortality, Growth hormone, MESH : Cause of Death, Settore MED/38 - Pediatria Generale e Specialistica, MESH: Adolescent, Original Paper, MESH: Humans, MESH : Humans, MESH: Child, Preschool, Infant, Newborn, Infant, MESH : Follow-Up Studies, MESH : Neoplasms, MESH: Male, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Europe, MESH: Female, Follow-Up Studies
Abstract: International audience; BACKGROUND:The long-term safety of growth hormone treatment is uncertain. Raised risks of death and certain cancers have been reported inconsistently, based on limited data or short-term follow-up by pharmaceutical companies.PATIENTS AND METHODS:The SAGhE (Safety and Appropriateness of Growth Hormone Treatments in Europe) study assembled cohorts of patients treated in childhood with recombinant human growth hormone (r-hGH) in 8 European countries since the first use of this treatment in 1984 and followed them for cause-specific mortality and cancer incidence. Expected rates were obtained from national and local general population data. The cohort consisted of 24,232 patients, most commonly treated for isolated growth failure (53%), Turner syndrome (13%) and growth hormone deficiency linked to neoplasia (12%). This paper describes in detail the study design, methods and data collection and discusses the strengths, biases and weaknesses consequent on this.CONCLUSION:The SAGhE cohort is the largest and longest follow-up cohort study of growth hormone-treated patients with follow-up and analysis independent of industry. It forms a major resource for investigating cancer and mortality risks in r-hGH patients. The interpretation of SAGhE results, however, will need to take account of the methods of cohort assembly and follow-up in each country.
Published: 2015
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10. SARS-CoV-2 infection after vaccination in patients with inflammatory rheumatic and musculoskeletal diseases

Author: Anja Strangfeld, Ana M. Rodrigues, Loreto Carmona, Ludovic Trefond, Charalampos Papagoras, Laure Gossec, N Roux, Kimme L. Hyrich, Saskia Lawson-Tovey, Bernd Raffeiner, Elsa F Mateus, Gözde Kübra Yardımcı, Pedro Machado, Xavier Mariette, NIHR Manchester Biomedical Research Centre [Manchester] (BRC [Manchester]), Manchester Academic Health Science Centre (MAHSC), University of Manchester [Manchester], Centre for Genetics and Genomics Versus Arthritis, Centre for Epidemiology Versus Arthritis, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Deutsches Rheuma-ForschungsZentrum (DRFZ), Deutsches Rheuma-ForschungsZentrum, Instituto de Salud Musculoesqueletica (InMusc), Central Hospital of Bolzano, Faculty of Medicine [Hacettepe University], Hacettepe University = Hacettepe Üniversitesi, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Service de Médecine Interne [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Hôpital privé Robert-Schuman, Metz, France., Sociedade Portuguesa de Reumatologia [Lisboa], Centro de Estudos de Doenças Crónicas (CEDOC), NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Democritus University of Thrace (DUTH), Liga Portuguesa Contra as Doenças Reumaticas (LPCDR), EULAR PARE [Zurich, Switzerland], Université Paris-Saclay, Service de Rhumatologie [CHU Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, University College of London [London] (UCL), NIHR Biomedical Research Centre [London], Guy's and St Thomas' NHS Foundation Trust-King‘s College London, University College London Hospitals (UCLH), London North West University Healthcare NHS Trust (LNWH), European Alliance of Associations for Rheumatology, Service de Rhumatologie [CHU Pitié Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Molé, Christine
Subjects: Male, medicine.medical_specialty, COVID-19 Vaccines, Immunology, Population, Comorbidity, General Biochemistry, Genetics and Molecular Biology, Rheumatology, Rheumatic Diseases, Internal medicine, Epidemiology, medicine, Humans, Immunology and Allergy, Registries, Adverse effect, education, Aged, Aged, 80 and over, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, education.field_of_study, business.industry, Abatacept, COVID-19, Middle Aged, vaccination, Vaccine efficacy, Vaccination, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Antirheumatic Agents, Hypertension, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, epidemiology, Rituximab, business, medicine.drug
Abstract: Patients with inflammatory rheumatic and musculoskeletal diseases (iRMDs) are often treated with immunomodulatory or immunosuppressive medications; consequently, they have been excluded alongside other immunocompromised patients from late stages of SARS-CoV-2 vaccine trials. SARS-CoV-2 vaccine efficacy in this population is unclear, though initial data are reassuring overall. However, a slightly lower SARS-CoV-2 immunogenicity of vaccines has been documented in some patients with iRMD.1 2 Some common rheumatic and musculoskeletal disease (RMD) medications have been highlighted as possible influential factors on immunogenicity, particularly rituximab (RTX), mycophenolate mofetil (MMF), methotrexate (MTX), abatacept and glucocorticoids.3–7 The European Alliance of Associations for Rheumatology (EULAR) launched a COVID-19 registry in March 2020, capturing COVID-19 outcomes in the European RMD population. Questions on reinfection and vaccination were added in January 2021. A further EULAR registry (COVAX) was launched in February 2021 to collect data on COVID-19 vaccination and related adverse events among patients with RMD. Here we describe a series of patients who contracted SARS-CoV-2 infection after COVID-19 vaccination between 19 January 2021 and 27 July 2021. The series consists of 38 adults with iRMDs, 8 from the COVID-19 registry (
Published: 2021
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11. Dysregulation of GSK3β-Target Proteins in Skin Fibroblasts of Myotonic Dystrophy Type 1 (DM1) Patients

Author: Geneviève Gourdon, Andreas Hentschel, Hanns Lochmüller, Denisa Hathazi, Valentina Grande, Nikoletta Nikolenko, Ulrike Schara-Schmidt, Theo Marteau, Andreas Roos, Emily O'Connor, Universitat Duisberg-Essen, Leibniz-Institut für Analytische Wissenschaften - ISAS - e.V., University of Cambridge School of Clinical Medicine, Université d'Ottawa [Ontario] (uOttawa), Essen University Hospital, Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), University College London Hospitals (UCLH), University Hospital Freiburg, Barcelona Institute of Science and Technology (BIST), University Children's Hospital of Essen [Essen, Germany], HAL UPMC, Gestionnaire, and Centre de Recherche en Myologie
Subjects: Male, Proteomics, 0301 basic medicine, [SDV]Life Sciences [q-bio], Muscle Fibers, Skeletal, Medizin, MAP2K2, Muscle Development, CTPS1, CAPN1, 0302 clinical medicine, Myotonic Dystrophy, CTNNB1, Skin, Myogenesis, Kinase, Middle Aged, 3. Good health, Cell biology, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Neurology, Female, Adult, musculoskeletal diseases, congenital, hereditary, and neonatal diseases and abnormalities, Myosin light-chain kinase, Protein Serine-Threonine Kinases, Biology, Myotonic dystrophy, Myotonin-Protein Kinase, 03 medical and health sciences, medicine, Humans, Muscle Strength, RNA, Messenger, Protein kinase A, GSK3B, Glycogen Synthase Kinase 3 beta, Gene Expression Profiling, Skeletal muscle, Fibroblasts, medicine.disease, HDAC2, 030104 developmental biology, fibroblast proteomics, GSK3␤, Neurology (clinical), Trinucleotide Repeat Expansion, Biomarkers, 030217 neurology & neurosurgery
Abstract: International audience; Myotonic dystrophy type 1 (DM1) is the most common monogenetic muscular disorder of adulthood. This multisystemic disease is caused by CTG repeat expansion in the 3-untranslated region of the DM1 protein kinase gene called DMPK. DMPK encodes a myosin kinase expressed in skeletal muscle cells and other cellular populations such as smooth muscle cells, neurons and fibroblasts. The resultant expanded (CUG)n RNA transcripts sequester RNA binding factors leading to ubiquitous and persistent splicing deregulation. The accumulation of mutant CUG repeats is linked to increased activity of glycogen synthase kinase 3 beta (GSK3␤), a highly conserved and ubiquitous serine/threonine kinase with functions in pathways regulating inflammation, metabolism, oncogenesis, neurogenesis and myogenesis. As GSK3␤-inhibition ameliorates defects in myogenesis, muscle strength and myotonia in a DM1 mouse model, this kinase represents a key player of DM1 pathobiochemistry and constitutes a promising therapeutic target. To better characterise DM1 patients, and monitor treatment responses, we aimed to define a set of robust disease and severity markers linked to GSK3␤by unbiased proteomic profiling utilizing fibroblasts derived from DM1 patients with low (80-150) and high (2600-3600) CTG-repeats. Apart from GSK3␤ increase, we identified dysregulation of nine proteins (CAPN1, CTNNB1, CTPS1, DNMT1, HDAC2, HNRNPH3, MAP2K2, NR3C1, VDAC2) modulated by GSK3␤. In silico-based expression studies confirmed expression in neuronal and skeletal muscle cells and revealed a relatively elevated abundance in fibroblasts. The potential impact of each marker in the myopathology of DM1 is discussed based on respective function to inform potential uses as severity markers or for monitoring GSK3␤ inhibitor treatment responses.
Published: 2021
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12. Considerations for a combined index for limited cutaneous systemic sclerosis to support drug development and improve outcomes

Author: Alain Lescoat, Francesco Del Galdo, Peter A. Merkel, Dominique Godard, Michael Hughes, Sue Farrington, Susan L. Murphy, Virginia D. Steen, David Cella, John D Pauling, Dinesh Khanna, Rachel Wessel, Yannick Allanore, Christopher P. Denton, Robert D Sandler, David Roofeh, François Zimmermann, Lorinda Chung, Maya H. Buch, Whitney Townsend, Chard-Hutchinson, Xavier, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], University of Michigan [Ann Arbor], University of Michigan System, Royal United Hospitals Bath (RUH), School of Veterinary and Life Sciences [Murdoch], Murdoch University, Sheffield Children's NHS Foundation Trust, Stanford University, University College London Hospitals (UCLH), Hospital of the University of Pennsylvania (HUP), Perelman School of Medicine, University of Pennsylvania-University of Pennsylvania, Georgetown University Medical Center, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Leeds, Association des Sclérodermie de France, Northwestern University Feinberg School of Medicine, Manchester Academic Health Science Centre (MAHSC), University of Manchester [Manchester], SRUK/WSF [UHUHR1], NIH/NIAMS 24 [AR063120], Y NIH/NIAMS T32 grant [AR007080], Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia]
Subjects: combined response index, medicine.medical_specialty, Treatment response, [SDV]Life Sciences [q-bio], media_common.quotation_subject, Immunology, limited cutaneous systemic sclerosis, classifications, Systemic scleroderma, Article, Scleroderma, law.invention, Neglect, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Randomized controlled trial, Quality of life, law, Immunology and Allergy, Medicine, scleroderma, 030212 general & internal medicine, Intensive care medicine, media_common, 030203 arthritis & rheumatology, integumentary system, business.industry, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Clinical trial, quality of life, Drug development, Systemic sclerosis, composite score, business
Abstract: Systemic sclerosis (systemic scleroderma) is characterized by a heterogeneous range of clinical manifestations. Systemic sclerosis is classified into limited cutaneous systemic sclerosis and diffuse cutaneous systemic sclerosis subgroups based on the extent of skin involvement. Randomized controlled trials in scleroderma have mainly focused on diffuse cutaneous systemic sclerosis partly because the measurement of skin involvement, critical for evaluating a therapeutic intervention, is more dynamic in this subset. Nonetheless, limited cutaneous systemic sclerosis, the most common cutaneous subset (about two-third), is also associated with significant morbidity and detrimental impact on health-related quality of life. The lack of interventional studies in limited cutaneous systemic sclerosis is partly due to a lack of relevant outcome measures to evaluate this subgroup. Combining several clinically meaningful outcomes selected specifically for limited cutaneous systemic sclerosis may improve representativeness in clinical trials and responsiveness of outcomes measured in randomized controlled trials. A composite index dedicated to limited cutaneous systemic sclerosis combining such relevant outcomes could advance clinical trial development for limited cutaneous systemic sclerosis by providing the opportunity to test and select among candidate drugs that could act as disease-modifying treatments for this neglected subgroup of systemic sclerosis. This proposed index would include items selected by expert physicians and patients with limited cutaneous systemic sclerosis across domains grounded in the lived experience of limited cutaneous systemic sclerosis. This article reviews the reasons behind the relative neglect of limited cutaneous systemic sclerosis, discusses the current state of outcome measures for limited cutaneous systemic sclerosis, identifies challenges, and proposes a roadmap for a combined limited cutaneous systemic sclerosis-specific treatment response index.
Published: 2020
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13. Management and outcomes of extreme preterm birth

Author: Andrei S Morgan, Marina Mendonça, Nicole Thiele, Anna L David, Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Elizabeth Garrett Anderson Institute for Womens' Health [Londres, Royaume-Uni], University College of London [London] (UCL), Maternité Port-Royal [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Warwick [Coventry], University of Leicester, European Foundation for the Care of Newborn Infants [Munich, Germany] (EFCNI), University College London Hospitals (UCLH), and Morgan, Andrei
Subjects: Adult, Male, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Practice, Infant, Newborn, General Medicine, Infant, Premature, Diseases, Magnesium Sulfate, Perinatal Care, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Neurodevelopmental Disorders, Pregnancy, Infant, Extremely Premature, Intensive Care, Neonatal, Peripartum Period, Humans, Premature Birth, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, Decision Making, Shared
Abstract: Extreme preterm birth, defined as birth before 28 weeks’ gestational age (box 1),1 affects about two to five in every 1000 pregnancies, and varies slightly by country and by definitions used. Severe maternal morbidity, including sepsis and peripartum haemorrhage, affects around a quarter of mothers delivering at these gestations.2 For the babies, survival and morbidity rates vary, particularly by gestational age at delivery but also according to other risk factors (birth weight and sex, for example) and by country.34 In this update, we focus on high income countries and provide a broad overview of extreme preterm birth epidemiology, recent changes, and best practices in obstetric and neonatal management, including new treatments such as antenatal magnesium sulphate or changes in delivery management such as delayed cord clamping and placental transfusion. We cover short and long term medical, psychological, and experiential consequences for individuals born extremely preterm, their mothers and families, as well as preventive measures that may reduce the incidence of extreme preterm birth.\ud \ud
Published: 2022
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14. Trial of Labor Compared With Elective Cesarean Delivery for Low-Lying Placenta

Author: Alizée Froeliger, Hugo Madar, Pauline Jeanneteau, Vanessa Ruiz, Maela Le Lous, Franck Perrotin, Norbert Winer, Michel Dreyfus, Philippe Merviel, Aurélien Mattuizzi, Eric Jauniaux, Loïc Sentilhes, Université de Bordeaux (UB), CHU Bordeaux [Bordeaux], Reseau de perinatalite des Pays de La Loire, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Physiopathologie des Adaptations Nutritionnelles (PhAN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Institut Fédératif de Recherche 148 Brest - Sciences et Ingénierie en Biologie Santé (IFR 148 Brest), Sciences et ingénierie en biologie santé (SCINBIOS), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Institute for Women's Health [London], University College London Hospitals (UCLH), and Centre Hospitalier Universitaire de Bordeaux (CHU de Bordeaux)
Subjects: Male, Labor, Obstetric, Cesarean Section, GYNECOLOGISTS, Placenta, VAGINAL DELIVERY, FRENCH COLLEGE, [SDV]Life Sciences [q-bio], Postpartum Hemorrhage, Infant, Newborn, Obstetrics and Gynecology, TRANEXAMIC ACID, Delivery, Obstetric, OBSTETRICIANS, Trial of Labor, INTERNAL OS DISTANCE, PROPENSITY SCORE, BLOOD-LOSS, Pregnancy, CLINICAL-PRACTICE, EDGE, Humans, Female, Retrospective Studies
Abstract: International audience; OBJECTIVE: To compare outcomes of women with low-lying placenta by planned mode of delivery and distance from the internal os distance. METHODS: Six tertiary maternity hospitals in France participated in this retrospective multicenter study of births from 2007-2012. Women with low-lying placenta, defined as an internal os distance of 20 mm or less, who gave birth after 35 weeks of gestation were included and classified in the planned trial-of-labor or elective cesarean delivery groups. The primary endpoint was severe postpartum hemorrhage (PPH) defined as blood loss exceeding 1,000 mL. Secondary outcomes were composite variables of severe maternal and neonatal morbidity. We used multivariable logistic regression and propensity scores to compare outcomes by planned mode of delivery. RESULTS: Among 128,233 births during the study period, 171 (0.13%) women had low-lying placenta: 70 (40.9%) in the trial-of-labor group and 101 (59.1%) who underwent elective cesarean delivery. The rate of severe PPH was 22.9% (16/70, 95% CI 13.7-34.4) for the trial-of-labor group and 23.0% (23/101, 95% CI 15.2-32.5) for the cesarean delivery group (P=.9); severe maternal and neonatal morbidity rates were likewise similar (2.9% vs 2.0% [P=.7] and 12.9% vs 9.9% [P=.5], respectively). Trial-of-labor was not significantly associated with a higher rate of severe PPH after multivariable logistic regression and propensity score-weighted analysis (adjusted odds ratio [aOR] 1.42, 95% CI 0.62-3.24 [P=.4]; and aOR 1.34, 95% CI 0.53-3.38 [P=.5], respectively). The vaginal delivery rate in the trial-of-labor group was 50.0% (19/38) in those with an internal os distance of 11-20 mm and 18.5% (5/27) in those with a distance of 1-10 mm. CONCLUSION: Our results support a policy of offering a trial of labor to women with low-lying placenta after 35 weeks of gestation and an internal os distance of 11-20 mm. An internal os distance of 1-10 mm reduces the likelihood of vaginal birth considerably, compared with 11-20 mm, but without increasing the incidence of severe PPH or severe maternal morbidity.
Published: 2022
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15. Surveillance of leishmaniasis cases from 15 European centres, 2014 to 2019: a retrospective analysis

Author: Van der Auwera, Gert, Davidsson, Leigh, Buffet, Pierre, Ruf, Marie-Thérèse, Gramiccia, Marina, Varani, Stefania, Chicharro, Carmen, Bart, Aldert, Harms, Gundel, Chiodini, Peter L, Brekke, Hanne, Robert-Gangneux, Florence, Cortes, Sofia, Verweij, Jaco J, Scarabello, Alessandra, Karlsson Söbirk, Sara, Guéry, Romain, van Henten, Saskia, Di Muccio, Trentina, Carra, Elena, van Thiel, Pieter, Vandeputte, Martin, Gaspari, Valeria, Blum, Johannes, LeishMan Surveillance network, Van der Auwera G., Davidsson L., Buffet P., Ruf M.-T., Gramiccia M., Varani S., Chicharro C., Bart A., Harms G., Chiodini P.L., Brekke H., Robert-Gangneux F., Cortes S., Verweij J.J., Scarabello A., Karlsson Sobirk S., Guery R., van Henten S., Di Muccio T., Carra E., van Thiel P., Vandeputte M., Gaspari V., Blum J., APH - Global Health, Infectious diseases, AII - Infectious diseases, Chard-Hutchinson, Xavier, Institute of Tropical Medicine [Antwerp] (ITM), Public Health Agency of Sweden, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Basel (Unibas), Istituto Superiore di Sanita [Rome], Azienda Ospedaliero Universitaria A. Meyer [Firenze, Italy], Instituto de Salud Carlos III [Madrid] (ISC), Amsterdam UMC - Amsterdam University Medical Center, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], University College London Hospitals (UCLH), Oslo University Hospital [Oslo], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École des Hautes Études en Santé Publique [EHESP] (EHESP), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), National Institute for Infectious Diseases 'Lazzaro Spallanzani', Lund University [Lund], Hôpital privé du Confluent [Nantes], Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna 'Bruno Ubertini' (IZSLER), and Istituto Superiore di Sanità (ISS)
Subjects: Adult, Male, Adolescent, Epidemiology, [SDV]Life Sciences [q-bio], Leishmaniasis, Cutaneous, imported, authochthonou, Young Adult, Virology, Humans, Authochthonous, Child, Leishmaniasis, leishmaniasis, travel, Aged, Retrospective Studies, Aged, 80 and over, Leishmania, Travel, Surveillance, Public Health, Environmental and Occupational Health, Infant, Newborn, Infant, Middle Aged, leishmaniasi, [SDV] Life Sciences [q-bio], Europe, Imported, Child, Preschool, surveillance, Leishmaniasis, Visceral, Female, authochthonous
Abstract: Background Surveillance of human leishmaniasis in Europe is mostly limited to country-specific information from autochthonous infections in the southern part. As at the end of 2021, no integrated analysis has been performed for cases seen across centres in different European countries. Aim To provide a broad perspective on autochthonous and imported leishmaniasis cases in endemic and non-endemic countries in Europe. Methods We retrospectively collected records from cutaneous, mucosal and visceral leishmaniasis cases diagnosed in 15 centres between 2014 and 2019. Centres were located in 11 countries: Belgium, France, Germany, Italy, the Netherlands, Norway, Portugal, Spain, Sweden, Switzerland and the United Kingdom. Data on country of infection, reason for travelling, infecting species, age and sex were analysed. Results We obtained diagnostic files from 1,142 cases, of which 76%, 21% and 3% had cutaneous, visceral, and mucosal disease, respectively. Of these, 68% were men, and 32% women, with the median age of 37 years (range: 0–90) at diagnosis. Visceral leishmaniasis was mainly acquired in Europe (88%; 167/190), while cutaneous leishmaniasis was primarily imported from outside Europe (77%; 575/749). Sixty-two percent of cutaneous leishmaniasis cases from outside Europe were from the Old World, and 38% from the New World. Geographic species distribution largely confirmed known epidemiology, with notable exceptions. Conclusions Our study confirms previous reports regarding geographic origin, species, and traveller subgroups importing leishmaniasis into Europe. We demonstrate the importance of pooling species typing data from many centres, even from areas where the aetiology is presumably known, to monitor changing epidemiology.
Published: 2022
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16. Managing hematological cancer patients during the COVID-19 pandemic: an ESMO-EHA interdisciplinary expert consensus

Author: Buske, C., Dreyling, M., Alvarez-Larran, A., Apperley, J., Arcaini, L., Besson, C., Bullinger, L., Corradini, P., Giovanni Della Porta, M., Dimopoulos, M., D'Sa, S., Eich, H. T., Foa, R., Ghia, P., da Silva, M. G., Gribben, J., Hajek, R., Harrison, C., Heuser, M., Kiesewetter, B., Kiladjian, J. J., Kroger, N., Moreau, P., Passweg, J. R., Peyvandi, F., Rea, D., Ribera, J. -M., Robak, T., San-Miguel, J. F., Santini, V., Sanz, G., Sonneveld, P., von Lilienfeld-Toal, M., Wendtner, C., Pentheroudakis, G., Passamonti, F., Hematology, Buske, C., Dreyling, M., Alvarez-Larran, A., Apperley, J., Arcaini, L., Besson, C., Bullinger, L., Corradini, P., Giovanni Della Porta, M., Dimopoulos, M., D'Sa, S., Eich, H. T., Foa, R., Ghia, P., da Silva, M. G., Gribben, J., Hajek, R., Harrison, C., Heuser, M., Kiesewetter, B., Kiladjian, J. J., Kroger, N., Moreau, P., Passweg, J. R., Peyvandi, F., Rea, D., Ribera, J. -M., Robak, T., San-Miguel, J. F., Santini, V., Sanz, G., Sonneveld, P., von Lilienfeld-Toal, M., Wendtner, C., Pentheroudakis, G., Passamonti, F., Universitätsklinikum Ulm - University Hospital of Ulm, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Imperial College London, Hammersmith Hospital NHS Imperial College Healthcare, Fondazione IRCCS Policlinico San Matteo [Pavia], Università degli Studi di Pavia = University of Pavia (UNIPV), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre Hospitalier de Versailles André Mignot (CHV), Charité Campus Virchow-Klinikum (CVK), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Freie Universität Berlin, Humboldt University Of Berlin, Medical Oncology Unit, Dept of Medical Oncology and Hematology [Fondazione IRCCS Istituto Nazionale Tumori, Milan], Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], Università degli Studi di Milano = University of Milan (UNIMI), Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), National and Kapodistrian University of Athens (NKUA), University College London Hospitals (UCLH), NHS Foundation Trust [London], The Royal Marsden, Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), IRCCS Ospedale San Raffaele [Milan, Italy], Queen Mary University of London (QMUL), Lékařská fakulta / Faculty of Medicine [University of Ostrava], Ostravská univerzita / University of Ostrava, Medizinische Universität Wien = Medical University of Vienna, Université Paris Cité (UPCité), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University Hospital Hamburg-Eppendorf, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Centre hospitalier universitaire de Nantes (CHU Nantes), University Hospital Basel [Basel], Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Department of Physiopatology and Transplantation, University of Milan (DEPT), Josep Carreras Leukaemia Research Institute (IJC), Universitat Autònoma de Barcelona (UAB), Medical University of Łódź (MUL), Clínica Universidad de Navarra [Pamplona], Azienda Ospedaliero-Universitaria Careggi [Firenze] (AOUC), Università degli Studi di Firenze = University of Florence (UniFI), Jena University Hospital [Jena], Ludwig Maximilian University [Munich] (LMU), Leibniz Institute for Natural Product Research and Infection Biology (Hans Knoell Institute), Universitá degli Studi dell’Insubria = University of Insubria [Varese] (Uninsubria), Boehringer Ingelheim, BI, Amgen, Bristol-Myers Squibb, BMS, Pfizer, Astellas Pharma US, APUS, AstraZeneca, Bayer, Novartis, Roche, Sanofi, Gilead Sciences, Celgene, AbbVie, Meso Scale Diagnostics, MSD, Takeda Pharmaceutical Company, TPC, Janssen Pharmaceuticals, Merck KGaA, Jazz Pharmaceuticals, Deutsche Forschungsgemeinschaft, DFG, Bundesministerium für Bildung und Forschung, BMBF, Daiichi-Sankyo, José Carreras Leukämie-Stiftung, Deutsche Krebshilfe, Ipsen, The panel would like to acknowledge the work of Klizia Marinoni and Delanie Young, from the Scientific and Medical Division at ESMO, for the project coordination and editorial assistance. None declared. CB reports honoraria from Roche/Genentech, Janssen, BeiGene, Novartis, Pfizer, Incyte, AbbVie, Gilead Sciences, Celltrion, MorphoSys, Regeneron, he reports consulting or advisory role: Gilead Sciences, Janssen, Roche, Pfizer, BeiGene, Celltrion, AbbVie, Incyte, Regeneron, MorphoSys, Novartis, he reports speaker's engagement: Roche, Janssen, BeiGene, Celltrion, AbbVie, Pfizer, Gilead Sciences, he reports research funding: Roche/Genentech, Janssen, Celltrion, Merck Sharp & Dohme (MSD), Pfizer, Amgen. MD reports honoraria as Advisory Board Member of AstraZeneca, Bayer, BeiGene, Celgene, Genmab, Gilead, Incyte, Janssen, Lilly, MorphoSys, Novartis, Roche, he reports honoraria for speaker's engagement from Amgen, AstraZeneca, Bayer, Celgene, Gilead, Janssen, Novartis, Roche, he reports institutional research grants from AbbVie, Bayer, Gilead, Celgene, Janssen, Roche. AA-L has declared no conflicts of interest. JA reports personal financial interests as advisory board and invited speaker from Incyte, advisory board from Mallinckrodt, advisory board and invited speaker from Novartis, advisory board and invited speaker from Pfizer, she reports non-financial interests as principal investigator from Incyte, principal investigator from Novartis. LA received advisory honoraria from Roche, Celgene, Janssen-Cilag, Verastem, Eusa Pharma, Incyte, ADC Therapeutics and Gilead, research support from Gilead, and travel expenses from Roche, Celgene, Janssen-Cilag, and Eusa Pharma, speakers bureau from Novartis. CB has declared no conflicts of interest. LB reports Advisory Committee activities for AbbVie, Amgen, Astellas, Bristol Myers Squibb (BMS), Celgene, Daiichi Sankyo, Gilead, Hexal, Janssen, Jazz Pharmaceuticals, Menarini, Novartis, Pfizer, Sanofi, Seattle Genetics and has research support from Bayer and Jazz Pharmaceuticals. PC has declared no conflicts of interest. MGDP has declared no conflicts of interest. MD reports personal fees from Amgen, personal fees from Takeda, personal fees from Janssen, personal fees from BeiGene, personal fees from BMS, outside the submitted work. SD reports personal financial interests as advisory board, invited speaker, fellow funding, and coordinating PI from BeiGene, writing engagement from Karger, advisory board and coordinating PI from Sanofi, funding, and other from Janssen, she reports non-financial interests as advisory role at British Society for Haematology Lymphoma Special Interest Group, advisory role at Lymphoma Action, member of board of directors at WMUK Charity. HTE has declared no conflicts of interest. RF reports honoraria for advisory boards and/or speaker bureau from Janssen, Gilead, AbbVie, Amgen, Novartis, Roche, Incyte, Pfizer, all outside the submitted work. PG reports grants and personal fees from AbbVie, grants and personal fees from Acerta/AstraZeneca, personal fees from BeiGene, personal fees from Celgene/Juno/BMS, grants and personal fees from Janssen, personal fees from Lilly/Loxo, personal fees from MEI, personal fees from Roche, personal fees from Sanofi, personal fees from ArQule/MSD, outside the submitted work, MGdS reports grants, personal fees, non-financial support and other from Gilead Sciences, grants from AstraZeneca, personal fees, non-financial support, and other from Janssen Cilag, personal fees and non-financial support from Roche, non-financial support from AbbVie, personal fees and non-financial support from BMS, personal fees and non-financial support from MSD, personal fees and non-financial support from Takeda, personal fees from Novartis, personal fees from ADC Therapeutics, outside the submitted work. JG reports personal fees from AbbVie, grants and personal fees from AstraZeneca, grants and personal fees from BMS/Celgene, grants and personal fees from Janssen, personal fees from Kite/Gilead, personal fees from MorphoSys, personal fees from Novartis, personal fees from TG Therapeutics, outside the submitted work. RH has had a consultant or advisory relationship with Janssen, Amgen, Celgene, AbbVie, BMS, Novartis, PharmaMar, and Takeda, has received honoraria from Janssen, Amgen, Celgene, BMS, PharmaMar, and Takeda, has received research funding from Janssen, Amgen, Celgene, BMS, Novartis, and Takeda. CH reports grants and personal fees from Novartis, grants and personal fees from BMS, personal fees from Sierra Oncology, personal fees from CTI pharmaceuticals, personal fees from Jannsen, personal fees from Geron, grants and personal fees from AOP Orphan Pharma, personal fees from Galecto, grants, personal fees and other from Constellation, outside the submitted work. MH reports personal fees from Novartis, personal fees from Pfizer, personal fees from Roche, personal fees from AbbVie, personal fees from Daiichi Sankyo, personal fees from Bayer Pharma AG, personal fees from Jazz Pharmaceuticals, personal fees from BMS, personal fees from Tolremo, outside the submitted work. BK has received honoraria for lectures from Ipsen, Novartis and MSD (all outside of the submitted work). J-JK reports consulting fees and honoraria from Novartis, consulting fees from AbbVie, honoraria from AOP Orphan Pharma, participation on a monitoring board or advisory board from BMS/Celgene, participation on a monitoring board or advisory board from Incyte. NK reports grants and honoraria from Neovii, honoraria from Sanofi, grants and honoraria from Jazz, grants and honoraria from Celgene, grants and honoraria from Riemser, honoraria from Gilead/Kite, honorarium from AOP Oprhan Pharma, grants and honorarium from Novartis, honorarium from Amgen. PM reports personal fees from Celgene, Amgen, Janssen, AbbVie, Sanofi, outside the submitted work. JP has declared no conflicts of interest. FP has declared no conflicts of interest. DR received honoraria from Incyte, Novartis Pharma, Pfizer, clinical trial steering committee membership: Novartis, membership on advisory boards: Incyte, Novartis Pharma, Pfizer. J-MR reports grants and honoraria from Novartis, Amgen, Pfizer, Takeda, Incyte, and Servier. TR has declared no conflicts of interest. JF-M reports consulting and advisory boards honoraria (received by CUN ) from AbbVie, Amgen, BMS, Celgene, Janssen, GlaxoSmithKline, Karyopharm, MSD, Novartis, Takeda, Sanofi, SecuraBio, Regeneron, Roche, outside the submitted work. VS has declared no conflicts of interest. GFS reports personal fees and other from AbbVie, other from Amgen, other from Astellas, other from Boehringer-Ingelheim, grants, personal fees and other from Celgene, other from Helsinn Healthcare, grants, personal fees, and other from Janssen-Cilag, grants and other from Novartis, other from Onconova, grants, personal fees and other from Roche, and other from Takeda, outside the submitted work. PS reports honoraria from Amgen, Celgene, Janssen, Karyopharm, SkylineDx, Takeda, and research support from Celgene, Janssen, Amgen, Takeda, BMS, SkylineDx, Karyopharm, all outside the submitted work. MvL-T has received travel grants and honoraria from Celgene, Gilead, Chugai, Janssen, Novartis, Amgen, Takeda, BMS, Medac, Oncopeptides, Merck, CDDF, Pfizer, Medac, Thermo Fisher, AstraZeneca, is a consultant for Celgene, Gilead, Oncopeptides, MSD, 4D Pharma, Janssen, Shionogi and received research funding from BMBF, Deutsche Jose Carreras Leuk?mie-Stiftung, IZKF Jena, Novartis, Gilead, Deutsche Krebshilfe, Celgene, Oncopeptides, Deutsche Forschungsgemeinschaft (DFG). CW has declared no conflicts of interest. GP reports grants from Amgen, grants, personal fees and non-financial support from Merck, grants and non-financial support from AstraZeneca, grants and personal fees from Roche, grants and personal fees from BMS, grants from Lilly, grants and personal fees from MSD, grants and personal fees from Novartis, outside the submitted work. FP reports grants from Novartis, Celgene, BMS, Abbvie, Karyopharma, Janssen., MGdS reports grants, personal fees, non-financial support and other from Gilead Sciences, grants from AstraZeneca, personal fees, non-financial support, and other from Janssen Cilag, personal fees and non-financial support from Roche, non-financial support from AbbVie, personal fees and non-financial support from BMS, personal fees and non-financial support from MSD, personal fees and non-financial support from Takeda, personal fees from Novartis, personal fees from ADC Therapeutics, outside the submitted work., MvL-T has received travel grants and honoraria from Celgene, Gilead, Chugai, Janssen, Novartis, Amgen, Takeda, BMS, Medac, Oncopeptides, Merck, CDDF, Pfizer, Medac, Thermo Fisher, AstraZeneca, is a consultant for Celgene, Gilead, Oncopeptides, MSD, 4D Pharma, Janssen, Shionogi and received research funding from BMBF, Deutsche Jose Carreras Leukämie-Stiftung, IZKF Jena, Novartis, Gilead, Deutsche Krebshilfe, Celgene, Oncopeptides, Deutsche Forschungsgemeinschaft (DFG)., and HAL UVSQ, Équipe
Subjects: Cancer Research, Consensus, consensus manuscript, COVID-19, hematological malignancies, COVID-19, consensus manuscript, hematological malignancies, education, [SDV.CAN]Life Sciences [q-bio]/Cancer, COVID-19 Testing, Humans, Pandemics, Hematologic Neoplasms, [SDV.CAN] Life Sciences [q-bio]/Cancer, Oncology, SDG 3 - Good Health and Well-being, Original Research
Abstract: The panel would like to acknowledge the work of Klizia Marinoni and Delanie Young, from the Scientific and Medical Division at ESMO, for the project coordination and editorial assistance. None declared. CB reports honoraria from Roche/Genentech, Janssen, BeiGene, Novartis, Pfizer, Incyte, AbbVie, Gilead Sciences, Celltrion, MorphoSys, Regeneron; he reports consulting or advisory role: Gilead Sciences, Janssen, Roche, Pfizer, BeiGene, Celltrion, AbbVie, Incyte, Regeneron, MorphoSys, Novartis; he reports speaker's engagement: Roche, Janssen, BeiGene, Celltrion, AbbVie, Pfizer, Gilead Sciences; he reports research funding: Roche/Genentech, Janssen, Celltrion, Merck Sharp & Dohme (MSD), Pfizer, Amgen. MD reports honoraria as Advisory Board Member of AstraZeneca, Bayer, BeiGene, Celgene, Genmab, Gilead, Incyte, Janssen, Lilly, MorphoSys, Novartis, Roche; he reports honoraria for speaker's engagement from Amgen, AstraZeneca, Bayer, Celgene, Gilead, Janssen, Novartis, Roche; he reports institutional research grants from AbbVie, Bayer, Gilead, Celgene, Janssen, Roche. AA-L has declared no conflicts of interest. JA reports personal financial interests as advisory board and invited speaker from Incyte, advisory board from Mallinckrodt, advisory board and invited speaker from Novartis, advisory board and invited speaker from Pfizer; she reports non-financial interests as principal investigator from Incyte, principal investigator from Novartis. LA received advisory honoraria from Roche, Celgene, Janssen-Cilag, Verastem, Eusa Pharma, Incyte, ADC Therapeutics and Gilead; research support from Gilead, and travel expenses from Roche, Celgene, Janssen-Cilag, and Eusa Pharma; speakers bureau from Novartis. CB has declared no conflicts of interest. LB reports Advisory Committee activities for AbbVie, Amgen, Astellas, Bristol Myers Squibb (BMS), Celgene, Daiichi Sankyo, Gilead, Hexal, Janssen, Jazz Pharmaceuticals, Menarini, Novartis, Pfizer, Sanofi, Seattle Genetics and has research support from Bayer and Jazz Pharmaceuticals. PC has declared no conflicts of interest. MGDP has declared no conflicts of interest. MD reports personal fees from Amgen, personal fees from Takeda, personal fees from Janssen, personal fees from BeiGene, personal fees from BMS, outside the submitted work. SD reports personal financial interests as advisory board, invited speaker, fellow funding, and coordinating PI from BeiGene, writing engagement from Karger, advisory board and coordinating PI from Sanofi, funding, and other from Janssen; she reports non-financial interests as advisory role at British Society for Haematology Lymphoma Special Interest Group, advisory role at Lymphoma Action, member of board of directors at WMUK Charity. HTE has declared no conflicts of interest. RF reports honoraria for advisory boards and/or speaker bureau from Janssen, Gilead, AbbVie, Amgen, Novartis, Roche, Incyte, Pfizer, all outside the submitted work. PG reports grants and personal fees from AbbVie, grants and personal fees from Acerta/AstraZeneca, personal fees from BeiGene, personal fees from Celgene/Juno/BMS, grants and personal fees from Janssen, personal fees from Lilly/Loxo, personal fees from MEI, personal fees from Roche, personal fees from Sanofi, personal fees from ArQule/MSD, outside the submitted work;, MGdS reports grants, personal fees, non-financial support and other from Gilead Sciences, grants from AstraZeneca, personal fees, non-financial support, and other from Janssen Cilag, personal fees and non-financial support from Roche, non-financial support from AbbVie, personal fees and non-financial support from BMS, personal fees and non-financial support from MSD, personal fees and non-financial support from Takeda, personal fees from Novartis, personal fees from ADC Therapeutics, outside the submitted work. JG reports personal fees from AbbVie, grants and personal fees from AstraZeneca, grants and personal fees from BMS/Celgene, grants and personal fees from Janssen, personal fees from Kite/Gilead, personal fees from MorphoSys, personal fees from Novartis, personal fees from TG Therapeutics, outside the submitted work. RH has had a consultant or advisory relationship with Janssen, Amgen, Celgene, AbbVie, BMS, Novartis, PharmaMar, and Takeda; has received honoraria from Janssen, Amgen, Celgene, BMS, PharmaMar, and Takeda; has received research funding from Janssen, Amgen, Celgene, BMS, Novartis, and Takeda. CH reports grants and personal fees from Novartis, grants and personal fees from BMS, personal fees from Sierra Oncology, personal fees from CTI pharmaceuticals, personal fees from Jannsen, personal fees from Geron, grants and personal fees from AOP Orphan Pharma, personal fees from Galecto, grants, personal fees and other from Constellation, outside the submitted work. MH reports personal fees from Novartis, personal fees from Pfizer, personal fees from Roche, personal fees from AbbVie, personal fees from Daiichi Sankyo, personal fees from Bayer Pharma AG, personal fees from Jazz Pharmaceuticals, personal fees from BMS, personal fees from Tolremo, outside the submitted work. BK has received honoraria for lectures from Ipsen, Novartis and MSD (all outside of the submitted work). J-JK reports consulting fees and honoraria from Novartis, consulting fees from AbbVie, honoraria from AOP Orphan Pharma, participation on a monitoring board or advisory board from BMS/Celgene, participation on a monitoring board or advisory board from Incyte. NK reports grants and honoraria from Neovii, honoraria from Sanofi, grants and honoraria from Jazz, grants and honoraria from Celgene, grants and honoraria from Riemser, honoraria from Gilead/Kite, honorarium from AOP Oprhan Pharma, grants and honorarium from Novartis, honorarium from Amgen. PM reports personal fees from Celgene, Amgen, Janssen, AbbVie, Sanofi, outside the submitted work. JP has declared no conflicts of interest. FP has declared no conflicts of interest. DR received honoraria from Incyte, Novartis Pharma, Pfizer; clinical trial steering committee membership: Novartis; membership on advisory boards: Incyte, Novartis Pharma, Pfizer. J-MR reports grants and honoraria from Novartis, Amgen, Pfizer, Takeda, Incyte, and Servier. TR has declared no conflicts of interest. JF-M reports consulting and advisory boards honoraria (received by CUN) from AbbVie, Amgen, BMS, Celgene, Janssen, GlaxoSmithKline, Karyopharm, MSD, Novartis, Takeda, Sanofi, SecuraBio, Regeneron, Roche, outside the submitted work. VS has declared no conflicts of interest. GFS reports personal fees and other from AbbVie, other from Amgen, other from Astellas, other from Boehringer-Ingelheim, grants, personal fees and other from Celgene, other from Helsinn Healthcare, grants, personal fees, and other from Janssen-Cilag, grants and other from Novartis, other from Onconova, grants, personal fees and other from Roche, and other from Takeda, outside the submitted work. PS reports honoraria from Amgen, Celgene, Janssen, Karyopharm, SkylineDx, Takeda, and research support from Celgene, Janssen, Amgen, Takeda, BMS, SkylineDx, Karyopharm, all outside the submitted work. MvL-T has received travel grants and honoraria from Celgene, Gilead, Chugai, Janssen, Novartis, Amgen, Takeda, BMS, Medac, Oncopeptides, Merck, CDDF, Pfizer, Medac, Thermo Fisher, AstraZeneca; is a consultant for Celgene, Gilead, Oncopeptides, MSD, 4D Pharma, Janssen, Shionogi and received research funding from BMBF, Deutsche Jose Carreras Leukämie-Stiftung, IZKF Jena, Novartis, Gilead, Deutsche Krebshilfe, Celgene, Oncopeptides, Deutsche Forschungsgemeinschaft (DFG). CW has declared no conflicts of interest. GP reports grants from Amgen, grants, personal fees and non-financial support from Merck, grants and non-financial support from AstraZeneca, grants and personal fees from Roche, grants and personal fees from BMS, grants from Lilly, grants and personal fees from MSD, grants and personal fees from Novartis, outside the submitted work. FP reports grants from Novartis, Celgene, BMS, Abbvie, Karyopharma, Janssen. GP reports grants from Amgen, grants, personal fees and non-financial support from Merck, grants and non-financial support from AstraZeneca, grants and personal fees from Roche, grants and personal fees from BMS, grants from Lilly, grants and personal fees from MSD, grants and personal fees from Novartis, outside the submitted work. Background: The COVID-19 pandemic has created enormous challenges for the clinical management of patients with hematological malignancies (HMs), raising questions about the optimal care of this patient group. Methods: This consensus manuscript aims at discussing clinical evidence and providing expert advice on statements related to the management of HMs in the COVID-19 pandemic. For this purpose, an international consortium was established including a steering committee, which prepared six working packages addressing significant clinical questions from the COVID-19 diagnosis, treatment, and mitigation strategies to specific HMs management in the pandemic. During a virtual consensus meeting, including global experts and lead by the European Society for Medical Oncology and the European Hematology Association, statements were discussed and voted upon. When a consensus could not be reached, the panel revised statements to develop consensual clinical guidance. Results and conclusion: The expert panel agreed on 33 statements, reflecting a consensus, which will guide clinical decision making for patients with hematological neoplasms during the COVID-19 pandemic.
Published: 2022
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17. Safety of Vaccination against SARS-CoV-2 in People with Rheumatic and Musculoskeletal Diseases: Results from the EULAR Coronavirus Vaccine (COVAX) Physician-Reported Registry

Author: Pedro M Machado, Saskia Lawson-Tovey, Anja Strangfeld, Elsa F Mateus, Kimme L Hyrich, Laure Gossec, Loreto Carmona, Ana Rodrigues, Bernd Raffeiner, Catia Duarte, Eric Hachulla, Eric Veillard, Eva Strakova, Gerd R Burmester, Gözde Kübra Yardımcı, Jose A Gomez-Puerta, Julija Zepa, Lianne Kearsley-Fleet, Ludovic Trefond, Maria Cunha, Marta Mosca, Martina Cornalba, Martin Soubrier, Nicolas Roux, Olivier Brocq, Patrick Durez, Richard Conway, Tiphaine Goulenok, Johannes WJ Bijlsma, Iain B McInnes, Xavier Mariette, University College London Hospitals (UCLH), Manchester Academic Health Science Centre (MAHSC), University of Manchester [Manchester], Centre for Genetics and Genomics Versus Arthritis, Deutsches Rheuma-ForschungsZentrum (DRFZ), Deutsches Rheuma-ForschungsZentrum, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Instituto de Salud Musculoesqueletica (InMusc), Central Hospital of Bolzano, Centro Hospitalar e Universitário [Coimbra], CHU Lille, Department of Rheumatology and Clinical Immunology, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Faculty of Medicine [Hacettepe University], Hacettepe University = Hacettepe Üniversitesi, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Service de Médecine Interne [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, University of Pisa - Università di Pisa, CHU Clermont-Ferrand, Hôpital Princesse Grace [Monaco], Cliniques Universitaires Saint-Luc [Bruxelles], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University Medical Center [Utrecht], Hôpital Bicêtre, UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, and UCL - (SLuc) Service de rhumatologie
Subjects: Male, COVID-19 Vaccines, antirheumatic agents, Epidemiology, [SDV]Life Sciences [q-bio], Immunology, General Biochemistry, Genetics and Molecular Biology, Rheumatology, Muscular Diseases, Rheumatic Diseases, Immunology and Allergy, Humans, autoimmune diseases, Musculoskeletal Diseases, Registries, skin and connective tissue diseases, Aged, SARS-CoV-2, Vaccination, COVID-19, Middle Aged, Female, epidemiology, Rheumatologists, Immunosuppressive Agents
Abstract: ObjectivesTo describe the safety of vaccines against SARS-CoV-2 in people with inflammatory/autoimmune rheumatic and musculoskeletal disease (I-RMD).MethodsPhysician-reported registry of I-RMD and non-inflammatory RMD (NI-RMDs) patients vaccinated against SARS-CoV-2. From 5 February 2021 to 27 July 2021, we collected data on demographics, vaccination, RMD diagnosis, disease activity, immunomodulatory/immunosuppressive treatments, flares, adverse events (AEs) and SARS-CoV-2 breakthrough infections. Data were analysed descriptively.ResultsThe study included 5121 participants from 30 countries, 90% with I-RMDs (n=4604, 68% female, mean age 60.5 years) and 10% with NI-RMDs (n=517, 77% female, mean age 71.4). Inflammatory joint diseases (58%), connective tissue diseases (18%) and vasculitis (12%) were the most frequent diagnostic groups; 54% received conventional synthetic disease-modifying antirheumatic drugs (DMARDs), 42% biological DMARDs and 35% immunosuppressants. Most patients received the Pfizer/BioNTech vaccine (70%), 17% AstraZeneca/Oxford and 8% Moderna. In fully vaccinated cases, breakthrough infections were reported in 0.7% of I-RMD patients and 1.1% of NI-RMD patients. I-RMD flares were reported in 4.4% of cases (0.6% severe), 1.5% resulting in medication changes. AEs were reported in 37% of cases (37% I-RMD, 40% NI-RMD), serious AEs in 0.5% (0.4% I-RMD, 1.9% NI-RMD).ConclusionThe safety profiles of SARS-CoV-2 vaccines in patients with I-RMD was reassuring and comparable with patients with NI-RMDs. The majority of patients tolerated their vaccination well with rare reports of I-RMD flare and very rare reports of serious AEs. These findings should provide reassurance to rheumatologists and vaccine recipients and promote confidence in SARS-CoV-2 vaccine safety in I-RMD patients.
Published: 2022
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18. Clinical diversity and treatment results in tegumentary leishmaniasis

Author: Diana N. J. Lockwood, Jean-Pierre Gangneux, Romain Guery, Mark S. Bailey, Andreas Neumayr, Stephen L. Walker, Christophe Ravel, Pierre Buffet, Gundel Harms, Jan Clerinx, Gert Van der Auwera, Laurence Lachaud, Johannes Blum, Leo G. Visser, Sara Karlsson Söbirk, Aldert Bart, Pieter P. A. M. van Thiel, APH - Global Health, AII - Amsterdam institute for Infection and Immunity, Infectious diseases, AII - Infectious diseases, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital privé du Confluent [Nantes], University College London Hospitals (UCLH), London School of Hygiene and Tropical Medicine (LSHTM), Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health (BIH), James Cook University (JCU), Swiss Tropical and Public Health Institute [Basel], Universiteit van Amsterdam (UvA), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institute of Tropical Medicine [Antwerp] (ITM), Lund University [Lund], Universiteit Leiden [Leiden], Hôpital Lapeyronie [Montpellier] (CHU), University of Basel (Unibas), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université de Paris (UP), 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)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Chard-Hutchinson, Xavier, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Humboldt University Of Berlin, Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université Paris Cité (UPCité), and Universiteit Leiden
Subjects: Adult, Male, medicine.medical_specialty, Old World, Adolescent, [SDV]Life Sciences [q-bio], 030231 tropical medicine, RC955-962, Antiprotozoal Agents, Leishmaniasis, Cutaneous, law.invention, 03 medical and health sciences, Middle East, Young Adult, 0302 clinical medicine, Randomized controlled trial, Cutaneous leishmaniasis, law, Arctic medicine. Tropical medicine, Medicine, Humans, 030212 general & internal medicine, Young adult, Child, Aged, Leishmania, Travel, biology, business.industry, Transmission (medicine), Public Health, Environmental and Occupational Health, Leishmaniasis, Middle Aged, South America, medicine.disease, biology.organism_classification, Dermatology, 3. Good health, Europe, [SDV] Life Sciences [q-bio], Infectious Diseases, Africa, Female, Leishmania infantum, Public aspects of medicine, RA1-1270, business, Research Article
Abstract: Background Cutaneous leishmaniasis (CL) is frequent in travellers and can involve oro-nasal mucosae. Clinical presentation impacts therapeutic management. Methodology Demographic and clinical data from 459 travellers infected in 47 different countries were collected by members of the European LeishMan consortium. The infecting Leishmania species was identified in 198 patients. Principal findings Compared to Old World CL, New World CL was more frequently ulcerative (75% vs 47%), larger (3 vs 2cm), less frequently facial (17% vs 38%) and less frequently associated with mucosal involvement (2.7% vs 5.3%). Patients with mucosal lesions were older (58 vs 30 years) and more frequently immunocompromised (37% vs 3.5%) compared to patients with only skin lesions. Young adults infected in Latin America with L. braziliensis or L. guyanensis complex typically had an ulcer of the lower limbs with mucosal involvement in 5.8% of cases. Typically, infections with L. major and L. tropica acquired in Africa or the Middle East were not associated with mucosal lesions, while infections with L. infantum, acquired in Southern Europe resulted in slowly evolving facial lesions with mucosal involvement in 22% of cases. Local or systemic treatments were used in patients with different clinical presentations but resulted in similarly high cure rates (89% vs 86%). Conclusion/Significance CL acquired in L. infantum-endemic European and Mediterranean areas displays unexpected high rates of mucosal involvement comparable to those of CL acquired in Latin America, especially in immunocompromised patients. When used as per recommendations, local therapy is associated with high cure rates., Author summary Cutaneous and muco-cutaneous leishmaniasis (CL and MCL) are disfiguring diseases caused by a worldwide distributed parasite called Leishmania and its 20 species. Clinical manifestations span a wide continuum from single nodular lesion to disseminated form with mucosal involvement. No randomized clinical trial has ever been done exclusively in travellers and medical management is poorly evidence-based or based very predominantly on data obtained in endemic countries. Articles and reviews almost invariably propose a dichotomic view, with Old World CL described as a benign disease in contrast to New World CL strongly associated with destructive mucosal lesions. Our study is the first prospective clinical study providing a detailed description of the clinical presentation and risk of mucosal involvement in CL in several hundreds of patients, with frequent formal identification of the infecting Leishmania species. The harmonized data collection in patients infected in many transmission foci worldwide enabled direct comparisons of clinical patterns induced by different Leishmania species, and on the outcome following treatment with either local or systemic regimens. The study is based on an international harmonized data collection that allowed a wide capture of parasitologically confirmed cases. In striking contrast with previous assumptions, the study shows that CL acquired in Europe displays unexpected high rates of mucosal involvement comparable to those of CL acquired in Latin America, especially in immunocompromised travellers. It also shows that when used as per recommendations, local therapy is associated with high cure rates.
Published: 2021
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19. The genomics of heart failure: design and rationale of the HERMES consortium

Author: Svati H. Shah, Olle Melander, Neneh Sallah, Quinn S. Wells, Jerome I. Rotter, Faye Zhao, Charlotte Andersson, Guðmundur Thorgeirsson, Ghazaleh Fatemifar, Alex S. F. Doney, Michael E. Dunn, David E. Lanfear, Ian Ford, Eric Boersma, Sonia Shah, Christopher Newton-Cheh, Douglas L. Mann, Niek Verweij, Carolina Roselli, Laura M. Yerges-Armstrong, Jian Yang, Christian Torp-Pedersen, Veikko Salomaa, Mary L. Biggs, Alaa Shalaby, Christoph Nowak, Stefan Gross, Patrick T. Ellinor, Mari Liis Tammesoo, Diane T. Smelser, Peter M. Visscher, Hans L. Hillege, Ruth C. Lovering, Honghuang Lin, Colin N. A. Palmer, Louis Philippe Lemieux Perreault, Jeffrey Brandimarto, Uwe Völker, Perttu Salo, Andrea Koekemoer, Rebecca Gutmann, Åsa K. Hedman, Nilesh J. Samani, Heming Xing, Faiez Zannad, Jaison Jacob, Harry Hemingway, Michael R. Brown, Franco Giulianini, Anubha Mahajan, Xing Chen, Alexander Niessner, Peter Almgren, Daniel I. Swerdlow, Gunnar Engström, Lars Lind, Tõnu Esko, Tomasz Czuba, Anna Helgadottir, Harvey D. White, David J. Stott, Johan Ärnlöv, Lars Køber, Chim C. Lang, Krishna G. Aragam, Kent D. Taylor, Anders Mälarstig, Frederick K. Kamanu, Kenneth B. Margulies, Michelle L. O'Donoghue, Andrew D. Morris, Sahar Ghasemi, J. Wouter Jukema, Jessica van Setten, Abbas Dehghan, Guillaume Paré, Luca A. Lotta, Giorgio E. M. Melloni, Albert Henry, Bruce M. Psaty, Paul M. Ridker, David J. Carey, Marie-Pierre Dubé, John S. Gottdiener, Xiaosong Wang, Per H. Svensson, Xu Chen, Patrik K. E. Magnusson, Claudia Langenberg, Alexander Teumer, Vilmantas Giedraitis, Simon de Denus, Michael W. Nagle, Marcus Dörr, Thomas P. Cappola, André G. Uitterlinden, Michael Morley, Eliana Portilla-Fernandez, J. Gustav Smith, Abirami Veluchamy, Peter Weeke, Ify R. Mordi, Unnur Thorsteinsdottir, Naveed Sattar, Folkert W. Asselbergs, Daniel I. Chasman, Daníel F. Guðbjartsson, Jonathan H. Chung, Marcus E. Kleber, Raul Weiss, Christopher P. Nelson, Spiros Denaxas, Bing Yu, Simon P. R. Romaine, Nicholas A Marston, Anjali T. Owens, Cecilia M. Lindgren, John J.V. McMurray, Joshua D. Backman, Michael V. Holmes, Stella Trompet, Hilma Holm, Kerri L. Wiggins, Jian'an Luan, Stephan B. Felix, Yifan Yang, Jemma B. Wilk, Maryam Kavousi, Markus Perola, Christian T. Ruff, Jean-Claude Tardif, G Sveinbjörnsson, Samuel C. Dudley, Nicholas J. Wareham, Teemu J. Niiranen, Andrew P. Morris, Danny Tuckwell, Maris Teder-Laving, R. Thomas Lumbers, James P. Cook, Géraldine Asselin, William A. Chutkow, Winfried März, Steven A. Lubitz, John G.F. Cleland, Bill Kraus, Ramachandran S. Vasan, Christopher M. Haggerty, Olympe Chazara, Chris Finan, Heather L. Bloom, Hans-Peter Brunner-La Rocca, Francoise Fougerousse, Kenneth Rice, Craig L. Hyde, Graciela E. Delgado, Mark Chaffin, Marc S. Sabatine, Alanna C. Morrison, Kay-Tee Khaw, Kari Stefansson, Felix Vaura, Barry London, Isabella Kardys, Aroon D. Hingorani, Hongsheng Gui, Steen Stender, René Fouodjio, Mohsen Ghanbari, Pim van der Harst, Nicholas L. Smith, Karoline Kuchenbaecker, Adriaan A. Voors, Benoit Tyl, University College of London [London] (UCL), University College London Hospitals (UCLH), Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Lund University [Lund], Pfizer, Karolinska Institutet [Stockholm], Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], University of Groningen [Groningen], University of Oxford [Oxford], Dalarna University, Massachusetts General Hospital [Boston], Montreal Heart Institute - Institut de Cardiologie de Montréal, Regeneron Genetics Center, 777 Old Saw Mill River Road, Tarrytown, University of Washington [Seattle], Emory University [Atlanta, GA], Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Pennsylvania [Philadelphia], The University of Texas Health Science Center at Houston (UTHealth), Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Department of Molecular and Functional Genomics, Geisinger, Danville, PA, Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), AstraZeneca, Novartis Institutes for BioMedical Research (NIBR), University of Glasgow, University of Liverpool, Université de Montréal (UdeM), Imperial College London, University of Heidelberg, Medical Faculty, University of Dundee, Universität Greifswald - University of Greifswald, University of Minnesota Medical School, University of Minnesota System, German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Institut de Recherches Internationales Servier [Suresnes] (IRIS), Uppsala University, University of Maryland School of Medicine, University of Maryland System, University of Iceland [Reykjavik], deCODE genetics [Reykjavik], Henry Ford Hospital, Carver College of Medicine, University of Iowa, Geisinger Autism & Developmental Medicine Institute [Danville, PA, USA] (ADMI), ICIN - Netherlands Heart Institute, Leiden University Medical Center (LUMC), Netherlands Heart Institute, Partenaires INRAE, University of Cambridge [UK] (CAM), Rigshospitalet [Copenhagen], Copenhagen University Hospital, University of Leicester, Duke University [Durham], University of Iowa [Iowa City], Genentech, Inc., Genentech, Inc. [San Francisco], Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Skane University Hospital [Malmo], University of Edinburgh, Medizinische Universität Wien = Medical University of Vienna, University of Turku, National Institute for Health and Welfare [Helsinki], McMaster University [Hamilton, Ontario], Kaiser Permanente Washington Health Research Institute [Seattle] (KPWHRI), Harbor UCLA Medical Center [Torrance, Ca.], University Medical Center [Utrecht], University of Pittsburgh Medical Center [Pittsburgh, PA, États-Unis] (UPMC), University of Tartu, Aalborg University [Denmark] (AAU), Leiden University, University of Queensland [Brisbane], Ohio State University [Columbus] (OSU), Auckland City Hospital, GlaxoSmithKline, Glaxo Smith Kline, University of Texas Health Science Center, Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), 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), Duke University Medical Center, Regeneron Pharmaceuticals [Tarrytown], Vanderbilt University [Nashville], European Project, Langenberg, Claudia [0000-0002-5017-7344], Luan, Jian'an [0000-0003-3137-6337], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Cardiovascular Centre (CVC), Life Course Epidemiology (LCE), Groningen Kidney Center (GKC), Cardiology, University of Oxford, University of Pennsylvania, Universiteit Leiden, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiologie, MUMC+: MA Med Staf Spec Cardiologie (9), RS: Carim - H02 Cardiomyopathy, Epidemiology, and Internal Medicine
Subjects: Male, Study Designs, Cardiomyopathy, Disease, 030204 cardiovascular system & hematology, 0302 clinical medicine, AFRICAN ANCESTRY, Epidemiology, 80 and over, WIDE ASSOCIATION, EPIDEMIOLOGY, Cardiac and Cardiovascular Systems, AGING RESEARCH, RISK, Aged, 80 and over, 0303 health sciences, Kardiologi, Genomics, Middle Aged, Prognosis, 3. Good health, Female, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, Heart failure, CLASSIFICATION, Heart Failure/genetics, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Genetic model, medicine, Genetics, Diseases of the circulatory (Cardiovascular) system, Humans, Allele frequency, Genotyping, METAANALYSIS, 030304 developmental biology, Aged, Association studies, Study Design, business.industry, Odds ratio, ADULTS, COHORTS, medicine.disease, RC666-701, REPLICATION, business, Biomarkers, Genome-Wide Association Study
Abstract: Aims The HERMES (HEart failure Molecular Epidemiology for Therapeutic targets) consortium aims to identify the genomic and molecular basis of heart failure.Methods and results The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of >1.10 for common variants (allele frequency > 0.05) and >1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 x 10(-8) under an additive genetic model.Conclusions HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.
Published: 2021
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20. Liver transplantation for patients with acute-on-chronic liver failure (ACLF) in Europe: Results of the ELITA/EF-CLIF collaborative study (ECLIS)

Author: Luca S. Belli, Christophe Duvoux, Thierry Artzner, William Bernal, Sara Conti, Paolo A. Cortesi, Sophie-Caroline Sacleux, George-Philippe Pageaux, Sylvie Radenne, Jonel Trebicka, Javier Fernandez, Giovanni Perricone, Salvatore Piano, Silvio Nadalin, Maria C. Morelli, Silvia Martini, Wojciech G. Polak, Krzysztof Zieniewicz, Christian Toso, Marina Berenguer, Claudia Iegri, Federica Invernizzi, Riccardo Volpes, Vincent Karam, René Adam, François Faitot, Liane Rabinovich, Faouzi Saliba, Lucy Meunier, Mickael Lesurtel, Frank E. Uschner, Costantino Fondevila, Baptiste Michard, Audrey Coilly, Magdalena Meszaros, Domitille Poinsot, Andreas Schnitzbauer, Luciano G. De Carlis, Roberto Fumagalli, Paolo Angeli, Vincente Arroyo, Rajiv Jalan, Raffaella Viganò, Chiara Mazzarelli, Andrea Lauterio, Alessandro Giacomoni, Francesca Donato, Pietro Lampertico, Luisa Pasulo, Stefano Fagiuoli, Michele Colledan, Maria Cristina Morelli, Giovanni Vitale, Damiano Patrono, Renato Romagnoli, Antonio Ottobrelli, Ioannis Petridis, Umberto Cillo, Giacomo Germani, Patrizia Burra, Philippe Bachellier, Pietro Addeo, Camille Besch, Francoise Faitot, Sophie Caroline Sacleux, Saliba Faouzi, Rene Adam, Didier Samuel, Celine Guichon, Stéfanie Faure, Josè Ursic-Bedoya, Jorde Colmenero, David Toapanta, María Hernández-Tejero, Carmen Vinaixa, Caroline den Hoed, Jubi E. de Haan, Andrea Della Penna, Frank Erhard Uschner, Martin Welker, Stefan Zeuzem, Wolf Bechstein, Nicolas Goossens, Joanna Raszeja-Wyszomirska, Dev Katarey, Banwari Agarwal, Surgery, Internal Medicine, Gastroenterology & Hepatology, Intensive Care, ASST Great Metropolitan Niguarda / ASST Grande Ospedale Metropolitano Niguarda [Milan, Italia], 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), Hôpital de Hautepierre [Strasbourg], King‘s College London, Ospedale Multimedica Sesto San Giovanni, Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Centre Hépato-Biliaire [Hôpital Paul Brousse] (CHB), Hôpital Paul Brousse-Assistance Publique - Hôpitaux de Paris, Physiopathologie et traitement des maladies du foie, Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Département d'Hépato-Gastroentérologie et de Transplantation Hépatique [CHU Saint-Eloi], Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Service d'Hépatologie [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Goethe-University Frankfurt am Main, European Foundation for Study of Chronic Liver Failure [Barcelona] (EF CLIF), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Liver Unit, Clínica Universitaria, CIBER-EHD, Azienda Ospedale Università di Padova = Hospital-University of Padua (AOUP), Universitätsklinikum Tübingen - University Hospital of Tübingen, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Azienda Ospedaliero-Universitaria di Bologna, Azienda Ospedalerio - Universitaria Città della Salute e della Scienza di Torino = University Hospital Città della Salute e della Scienza di Torino, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Medical University of Warsaw - Poland, Geneva University Hospitals and Geneva University, Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, Hospital Papa Giovanni XXIII (Hosp P Giovanni XXIII), Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (ISMETT), Pôle des Pathologies Digestives Hépatiques et Transplantation [Hôpital Hautepierre-Strasbourg], Department of Physiopatology and Transplantation, University of Milan (DEPT), Università degli Studi di Milano = University of Milan (UNIMI), Ospedale S. Giovanni Battista-Molinette, Azienda Ospedaliera di Padova, Università degli Studi di Padova = University of Padua (Unipd), Hospital Clinic i Provincial de Barcelona (SCReN), University College London Hospitals (UCLH), Belli, L, Duvoux, C, Artzner, T, Bernal, W, Conti, S, Cortesi, P, Sacleux, S, Pageaux, G, Radenne, S, Trebicka, J, Fernandez, J, Perricone, G, Piano, S, Nadalin, S, Morelli, M, Martini, S, Polak, W, Zieniewicz, K, Toso, C, Berenguer, M, Iegri, C, Invernizzi, F, Volpes, R, Karam, V, Adam, R, Faitot, F, Rabinovich, L, Saliba, F, Meunier, L, Lesurtel, M, Uschner, F, Fondevila, C, Michard, B, Coilly, A, Meszaros, M, Poinsot, D, Schnitzbauer, A, De Carlis, L, Fumagalli, R, Angeli, P, Arroyo, V, Jalan, R, Fagiuoli, S, Goossens, Nicolas, and Salvy-Córdoba, Nathalie
Subjects: Male, 0301 basic medicine, Multi-drug resistant organisms, medicine.medical_treatment, Waiting list, Salvage therapy, Liver transplantation, Severity of Illness Index, MESH: Proportional Hazards Models, Cohort Studies, 0302 clinical medicine, MESH: Risk Factors, Risk Factors, Medicine, MESH: Cohort Studies, Acute-on-Chronic Liver Failure, MESH: Aged, High rate, MESH: Middle Aged, ddc:617, Hazard ratio, MESH: Acute-On-Chronic Liver Failure, Middle Aged, Prognosis, Predictive factors, Italy, Female, 030211 gastroenterology & hepatology, Adult, MESH: Liver Transplantation, medicine.medical_specialty, MESH: Prognosis, 03 medical and health sciences, MESH: Severity of Illness Index, Internal medicine, Humans, Acute on chronic liver failure, Renal replacement therapy, Aged, Proportional Hazards Models, Retrospective Studies, MESH: Humans, Hepatology, business.industry, MESH: Italy, MESH: Adult, MESH: Retrospective Studies, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Retrospective cohort study, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Multi-drug resistant organism, MESH: Male, 030104 developmental biology, Predictive factor, business, MESH: Female
Abstract: Background & Aims: Liver transplantation (LT) has been proposed as an effective salvage therapy even for the sickest patients with acute-on-chronic liver failure (ACLF). This large collaborative study was designed to assess the current clinical practice and outcomes of patients with ACLF who are wait-listed for LT in Europe. Methods: This was a retrospective study including 308 consecutive patients with ACLF, listed in 20 centres across 8 European countries, from January 2018 to June 2019. Results: A total of 2,677 patients received a LT: 1,216 (45.4%) for decompensated cirrhosis. Of these, 234 (19.2%) had ACLF at LT: 58 (4.8%) had ACLF-1, 78 (6.4%) had ACLF-2, and 98 (8.1%) had ACLF-3. Wide variations were observed amongst countries: France and Germany had high rates of ACLF-2/3 (27-41%); Italy, Switzerland, Poland and the Netherlands had medium rates (9-15%); and the United Kingdom and Spain had low rates (3-5%) (p 4 mmol/L (hazard ratio [HR] 3.14; 95% CI 1.37-7.19), recent infection from multidrug resistant organisms (HR 3.67; 95% CI 1.63-8.28), and renal replacement therapy (HR 2.74; 95% CI 1.37-5.51) were independent predictors of post-LT mortality. During the same period, 74 patients with ACLF died on the waiting list. In an intention-to-treat analysis, 1-year survival of patients with ACLF on the LT waiting list was 73% for ACLF-1 or-2 and 50% for ACLF-3. Conclusion: The results reveal wide variations in the listing of patients with ACLF in Europe despite favourable post-LT survival. Risk factors for mortality were identified, enabling a more pre-cise prognostic assessment of patients with ACLF. Lay summary: Acute-on-chronic liver failure (ACLF) is a severe clinical condition for which liver transplantation is an effective therapeutic option. This study has demonstrated that in Europe, referral and access to liver transplantation (LT) for patients with ACLF needs to be harmonised to avoid inequities. Post-LT survival for patients with ACLF was >80% after 1 year and some factors have been identified to help select patients with favourable outcomes. (C) 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All reserved.
Published: 2021
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21. Spironolactone for resistant hypertension in advanced chronic kidney disease—red, amber or green?

Author: Rajiv Agarwal, Patrick Rossignol, Bryan Williams, William B. White, Indiana University School of Medicine, Indiana University System, Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), 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), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), University College of London [London] (UCL), University College London Hospitals (UCLH), University of Connecticut (UCONN), and BOZEC, Erwan
Subjects: Transplantation, medicine.medical_specialty, hypertension, business.industry, Resistant hypertension, blood pressure, hyperkalemia, medicine.disease, Gastroenterology, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, chemistry.chemical_compound, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, chemistry, Nephrology, Internal medicine, CKD, Spironolactone, Medicine, guidelines, business, Kidney disease
Abstract: International audience
Published: 2020
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22. Intravenous supplementation type and volume are associated with 1-year outcome and major complications in patients with chronic intestinal failure

Author: Nuria Virgili, Konrad Matysiak, Cristina Cuerda, Henrik Højgaard Rasmussen, Florian Poullenot, Ronan Thibault, Umberto Aimasso, Amelia Jukes, Andre Dong Won Lee, Brooke Chapman, Geert J. A. Wanten, Simona Di Caro, Maryana Doitchinova-Simeonova, Alastair Forbes, Corrado Spaggiari, Ezra Steiger, Elena Nardi, Cécile Chambrier, Simon Lal, Paolo Orlandoni, Peter Sahin, Marina Taus, Mireille J. Serlie, Kinga Szczepanek, A. Crivelli, Nicola Wyer, Przemysław Matras, Lynn Jones, Carmen Garde, Gabriel Olveira, Marek Kunecki, José P. Suárez-Llanos, Francisca Joly, Ana Zugasti Murillo, Joanne Daniels, Loris Pironi, Zeljko Krznaric, Emma Osland, Sheldon C. Cooper, Stéphane M. Schneider, Sarah Jane Hughes, Lars Ellegård, Miriam Theilla, Luisa Masconale, Anna Zmarzly, Aurora E. Serralde-Zúñiga, André Van Gossum, Anna Simona Sasdelli, Lidia Santarpia, Nada Rotovnik Kozjek, Francesco William Guglielmi, Margie O'Callaghan, Charlene Compher, Estrella Petrina Jáuregui, Pironi, L., Steiger, E., Joly, F., Wanten, G. J. A., Chambrier, C., Aimasso, U., Sasdelli, A. S., Szczepanek, K., Jukes, A., Theilla, M., Kunecki, M., Daniels, J., Serlie, M. J., Cooper, S. C., Poullenot, F., Rasmussen, H. Ho., Compher, C. W., Crivelli, A., Hughes, S. -J., Santarpia, L., Guglielmi, F. W., Rotovnik Kozjek, N., Ellegard, L., Schneider, S. M., Matras, P., Forbes, A., Wyer, N., Zmarzly, A., Taus, M., O'Callaghan, M., Osland, E., Thibault, R., Cuerda, C., Jones, L., Chapman, B., Sahin, P., Virgili, N. M., Lee, A. D. W., Orlandoni, P., Matysiak, K., Di Caro, S., Doitchinova-Simeonova, M., Masconale, L., Spaggiari, C., Garde, C., Serralde-Zuniga, A. E., Olveira, G., Krznaric, Z., Petrina Jauregui, E., Zugasti Murillo, A., Suarez-Llanos, J. P., Nardi, E., Van Gossum, A., Lal, S., Pironi, Lori, Steiger, Ezra, Joly, Francisca, Wanten, Geert J A, Chambrier, Cecile, Aimasso, Umberto, Sasdelli, Anna Simona, Szczepanek, Kinga, Jukes, Amelia, Theilla, Miriam, Kunecki, Marek, Daniels, Joanne, Serlie, Mireille J, Cooper, Sheldon C, Poullenot, Florian, Rasmussen, Henrik Højgaard, Compher, Charlene W, Crivelli, Adriana, Hughes, Sarah-Jane, Santarpia, Lidia, Guglielmi, Francesco William, Rotovnik Kozjek, Nada, Ellegard, Lar, Schneider, Stéphane M, Matras, Przemysław, Forbes, Alastair, Wyer, Nicola, Zmarzly, Anna, Taus, Marina, O'Callaghan, Margie, Osland, Emma, Thibault, Ronan, Cuerda, Cristina, Jones, Lynn, Chapman, Brooke, Sahin, Peter, Virgili, Núria M, Lee, Andre Dong Won, Orlandoni, Paolo, Matysiak, Konrad, Di Caro, Simona, Doitchinova-Simeonova, Maryana, Masconale, Luisa, Spaggiari, Corrado, Garde, Carmen, Serralde-Zúñiga, Aurora E, Olveira, Gabriel, Krznaric, Zeljko, Petrina Jáuregui, Estrella, Zugasti Murillo, Ana, Suárez-Llanos, José P, Nardi, Elena, Van Gossum, André, Lal, Simon, University of Bologna, Cleveland Clinic, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Radboud university [Nijmegen], Hospices Civils de Lyon (HCL), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Aalborg University [Denmark] (AAU), Sahlgrenska Academy at University of Gothenburg [Göteborg], Centre Hospitalier Universitaire de Nice (CHU Nice), Medical University of Lublin, University of East Anglia [Norwich] (UEA), University Hospital Coventry, CHU Pontchaillou [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-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), Hospital General Universitario 'Gregorio Marañón' [Madrid], Austin Health, Universidade de São Paulo (USP), Poznan University of Life Sciences (Uniwersytet Przyrodniczy w Poznaniu) (PULS), University College London Hospitals (UCLH), Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán - National Institute of Medical Science and Nutrition Salvador Zubiran [Mexico], University of Manchester [Manchester], European Society for Clinical Nutrition and Metabolism (ESPEN)., Endocrinology, AGEM - Endocrinology, metabolism and nutrition, University of Bologna/Università di Bologna, Radboud University [Nijmegen], Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Universidade de São Paulo = University of São Paulo (USP)
Subjects: Male, 0301 basic medicine, [SDV]Life Sciences [q-bio], Severity of Illness Index, Liver disease, 0302 clinical medicine, Drug Dosage Calculations, motility disorder, 2. Zero hunger, Gastroenterology, Short bowel syndrome, 3. Good health, Chronic intestinal failure, Intestines, Pharmaceutical Solutions, Venous thrombosis, Intestinal obstruction, motility disorders, Administration, Intravenous, Female, 030211 gastroenterology & hepatology, Parenteral Nutrition, Home, Adult, Fat Emulsions, Intravenous, medicine.medical_specialty, parenteral nutrition, macromolecular substances, Clinical nutrition, short bowel syndrome, 03 medical and health sciences, Cholestasis, intestinal failure, Internal medicine, medicine, Humans, 030109 nutrition & dietetics, business.industry, liver failure, medicine.disease, Intestinal Diseases, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Parenteral nutrition, Alimentació parenteral, Intestinal Absorption, Catheter-Related Infections, Parenteral feeding, Chronic Disease, Obstrucció intestinal, Fluid Therapy, business, Body mass index
Abstract: Background and aimNo marker to categorise the severity of chronic intestinal failure (CIF) has been developed. A 1-year international survey was carried out to investigate whether the European Society for Clinical Nutrition and Metabolism clinical classification of CIF, based on the type and volume of the intravenous supplementation (IVS), could be an indicator of CIF severity.MethodsAt baseline, participating home parenteral nutrition (HPN) centres enrolled all adults with ongoing CIF due to non-malignant disease; demographic data, body mass index, CIF mechanism, underlying disease, HPN duration and IVS category were recorded for each patient. The type of IVS was classified as fluid and electrolyte alone (FE) or parenteral nutrition admixture (PN). The mean daily IVS volume, calculated on a weekly basis, was categorised as 3 L/day. The severity of CIF was determined by patient outcome (still on HPN, weaned from HPN, deceased) and the occurrence of major HPN/CIF-related complications: intestinal failure-associated liver disease (IFALD), catheter-related venous thrombosis and catheter-related bloodstream infection (CRBSI).ResultsFifty-one HPN centres included 2194 patients. The analysis showed that both IVS type and volume were independently associated with the odds of weaning from HPN (significantly higher for PN 1 L/day), patients’ death (lower for FE, p=0.079), presence of IFALD cholestasis/liver failure and occurrence of CRBSI (significantly higher for PN 2–3 and PN >3 L/day).ConclusionsThe type and volume of IVS required by patients with CIF could be indicators to categorise the severity of CIF in both clinical practice and research protocols.
Published: 2020
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23. HIST1H1E heterozygous protein‐truncating variants cause a recognizable syndrome with intellectual disability and distinctive facial gestalt: A study to clarify the HIST1H1E syndrome phenotype in 30 individuals

Author: John M. Graham, Anna Ardissone, Dieter Kotzot, Paul R. Mark, Anna Zachariou, Guillermo Lay-Son, Allyn McConkie-Rosell, John Pappas, Karen Low, Fiona Stewart, Chey Loveday, Brian G. Skotko, Melissa Lees, Helen Stewart, Ho Ming Luk, Cheryl Cytrynbaum, Rachel Horton, Siddharth Banka, Gerard Marion, Deborah J. Shears, Marie T. McDonald, Ricardo A. Verdugo, Christine Coubes, Yuri A. Zarate, Christophe Phillipe, Katrina Tatton-Brown, Clare Allen, Deepika D.Cunha Burkardt, Rosanna Weksberg, I. Karen Temple, Alexia Bourgois, David J. Amor, Frédéric Tran Mau-Them, Laurence Faivre, Case Western Reserve University [Cleveland], The institute of cancer research [London], University College London Hospitals (UCLH), Murdoch Children's Research Institute (MCRI), University of Melbourne, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', University of Manchester [Manchester], Manchester University NHS Foundation Trust (MFT), Service de Génétique [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), The Hospital for sick children [Toronto] (SickKids), Hôpital d'Enfants [CHU Dijon], Hôpital du Bocage, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), University Hospital Southampton NHS Foundation Trust, Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Pontificia Universidad Católica de Chile (UC), Great Ormond Street Hospital for Children [London] (GOSH), University Hospitals Bristol, Department of Health Clinical Genetic Service Centre, Spectrum Health [Grand Rapids], Department of Molecular Genetics and Microbiology [Durham] (MGM), Duke University [Durham], New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Department of Clinical Genetics [Churchill Hospital], Churchill Hospital Oxford Centre for Haematology, Harvard Medical School [Boston] (HMS), Belfast City Hospital, Oxford University Hospitals NHS Trust, University of Oxford [Oxford], University of Southampton, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Universitad de Chile, Arkansas Children's Hospital, Cedars-Sinai Medical Center, St George’s University Hospitals, and Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Heterozygote, Bioinformatics, Corpus callosum, Rahman syndrome, Histones, 03 medical and health sciences, Frontal Bossing, 0302 clinical medicine, HIST1H1E, Gene cluster, Intellectual disability, Genetics, Humans, Learning, Medicine, Epigenetics, Genetics (clinical), 030304 developmental biology, Behavior, [SDV.GEN]Life Sciences [q-bio]/Genetics, 0303 health sciences, epigenetic regulator gene, biology, business.industry, Facies, Heterozygote advantage, Syndrome, medicine.disease, Phenotype, Histone, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, intellectual disability, Mutation, biology.protein, Growth and Development, business, 030217 neurology & neurosurgery
Abstract: International audience; Histone Gene Cluster 1 Member E, HIST1H1E, encodes Histone H1.4, is one of a family of epigenetic regulator genes, acts as a linker histone protein, and is responsible for higher order chromatin structure. HIST1H1E syndrome (also known as Rahman syndrome, OMIM #617537) is a recently described intellectual disability (ID) syndrome. Since the initial description of five unrelated individuals with three different heterozygous protein-truncating variants (PTVs) in the HIST1H1E gene in 2017, we have recruited 30 patients, all with HIST1H1E PTVs that result in the same shift in frame and that cluster to a 94-base pair region in the HIST1H1E carboxy terminal domain. The identification of 30 patients with HIST1H1E variants has allowed the clarification of the HIST1H1E syndrome phenotype. Major findings include an ID and a recognizable facial appearance. ID was reported in all patients and is most frequently of moderate severity. The facial gestalt consists of a high frontal hairline and full lower cheeks in early childhood and, in later childhood and adulthood, affected individuals have a strikingly high frontal hairline, frontal bossing, and deep-set eyes. Other associated clinical features include hypothyroidism, abnormal dentition, behavioral issues, cryptorchidism, skeletal anomalies, and cardiac anomalies. Brain magnetic resonance imaging (MRI) is frequently abnormal with a slender corpus callosum a frequent finding.
Published: 2019
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24. Toward standardization of assays measuring extracellular vesicle-associated tissue factor activity

Author: Chris Gardiner, Johannes Thaler, Barry Woodhams, Nigel Mackman, Françoise Dignat-George, Rienk Nieuwland, François Mullier, Academic Medical Centre [Amsterdam], University of Amsterdam [Amsterdam] (UvA), University College London Hospitals (UCLH), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Catholique de Louvain = Catholic University of Louvain (UCL), University of North Carolina at Chapel Hill (UNC), Independent Researcher, Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medizinische Universität Wien = Medical University of Vienna, Laboratory Specialized Diagnostics & Research, ACS - Microcirculation, ProdInra, Migration, UCL - (MGD) Laboratoire de biologie clinique, and UCL - SSS/IREC/MONT - Pôle Mont Godinne
Subjects: Blood Platelets, 030204 cardiovascular system & hematology, Bioinformatics, Thromboplastin, Workflow, 03 medical and health sciences, Tissue factor, Extracellular Vesicles, 0302 clinical medicine, Prothrombinase, Predictive Value of Tests, Surveys and Questionnaires, Medicine, Humans, Platelet, Blood Coagulation, ComputingMilieux_MISCELLANEOUS, Disseminated intravascular coagulation, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Reproducibility of Results, Recommendations and Guidelines, Hematology, Extracellular vesicle, medicine.disease, Microvesicles, 3. Good health, Hemostasis, Blood Coagulation Tests, business, Biomarkers, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Tenase
Abstract: The clinical and scientific interest in extracellular vesicles (EVs) is growing exponentially. The term EVs is an umbrella term for various types of vesicles that are present in body fluids and other (bio)fluids. This umbrella term is used because clear hallmarks to distinguish different types of EVs from each other are lacking. Thus, the term “EVs” encompasses earlier “microparticles” or “microvesicles” and exosomes, which are vesicles released directly from the plasma membrane or by secretion of intraluminal vesicles stored in multivesicular endosomes, respectively.1, 2 There is evidence that EVs play a role in intercellular communication and contribute to coagulation and likely inflammation.3, 4, 5, 6 The oldest‐known function of “platelet dust,” now known as platelet‐derived EVs, is their ability to support coagulation by exposing negatively charged phospholipids, such as phosphatidylserine (PS). Such PS exposing EVs facilitates formation of tenase and prothrombinase complexes. Furthermore, different subtypes of EVs, such as leukocyte, endothelial, or tumor‐derived EVs, can also trigger coagulation by exposing tissue factor (TF).7 Tissue factor‐exposing EVs (TF‐EVs) are present in body fluids, such as saliva and urine, under physiological conditions. The presence of TF‐EVs in saliva may explain the reflex to lick a wound, thereby exposing blood to extravascular TF and accelerating hemostasis and reducing the risk of infection.8 Although Tissue factor was initially thought to be exclusively present outside the vasculature (“envelope model”); there is increasing evidence that during medical intervention and in various clinical conditions, such as surgery, or in patients suffering from sepsis or cancer, the presence of coagulant TF‐EVs is associated with disseminated intravascular coagulation and venous thrombosis.9, 10 There are two reasons why a proposed standardization is timely and relevant. First, there is a growing interest to improve the reproducibility of results in science in general, and this also holds true for the new field of EV research. During the last few years, “minimal requirements” have been published by the International Society of Extracellular Vesicles (ISEV) regarding the reporting on studies involving EVs,11, 12, 13 as well as a structure to record and score reporting of preanalytical variables 14, 15, 16, 17 In addition, guidelines and position papers have been published18, 19 and an increasing number of standardization studies have been and are being performed involving various aspects of EV detection and characterization.2, 14, 20, 21 At present, various in‐house and commercially available assays have been developed to measure the EV‐associated TF (EV‐TF) activity, but hitherto the results of these methods have not been easily compared and required standardization. Second, to identify cancer patients at risk of developing venous thromboembolism, an EV‐TF‐based factor Xa generation assay and an EV‐TF‐based plasma clotting test have been developed and applied in clinical trials and have shown promising results for the prediction of VTE in pancreatic cancer patients. This underscores the relevance of studying TF‐EVs as a potential clinically relevant biomarker.22, 23 Taken together, we provide a summary of the outcomes of the questionnaire and discussion with the goal to improve future standardization of studies measuring the TF activity of EVs.
Published: 2019
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25. Global epidemiology of hip fractures: a study protocol using a common analytical platform among multiple countries

Author: Kebede Beyene, Jiannong Liu, Amy Hai Yan Chan, Chor-Wing Sing, Caroline Y. Doyon, Hongxin Zhao, Henrik Toft Sørensen, E. Michael Lewiecki, Anna-Maija Tolppanen, Katia M.C. Verhamme, Kenneth K.C. Man, Ju-Young Shin, Kiyoshi Kubota, Jeff Lange, Ian C. K. Wong, Tzu-Chieh Lin, Grace Hsin-Min Wang, Jenni Ilomäki, Mirhelen Mendes de Abreu, Douglas P. Kiel, Pauline Bosco-Lévy, Sharon Bartholomew, Nicholas Moore, Corina W Bennett, Sawaeng Watcharathanakij, Daniel Prieto-Alhambra, Sirpa Hartikainen, Ganga Ganesan, Nobuhiro Ooba, Edward Chia Cheng Lai, Alma B Pedersen, Kelvin Bryan Tan, James O’Kelly, Manju Chandran, Ching-Lung Cheung, J. Simon Bell, Han Eol Jeong, Cécile Droz-Perroteau, The University of Hong Kong (HKU), Amgen Inc. [Thousand Oaks, CA, USA], Public Health Agency of Canada, Monash University [Melbourne], University of Auckland [Auckland], Plateforme Bordeaux PharmacoEpi [Bordeaux] (BPE), Centre d'Investigation Clinique [Bordeaux], Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bordeaux (UB), National University Hospital [Singapore] (NUH), Ministry of Health [Singapore], University of Eastern Finland, Sungkyunkwan University [Suwon] (SKKU), Harvard Medical School [Boston] (HMS), National Cheng Kung University (NCKU), The University of New Mexico [Albuquerque], Hennepin County Medical Center, Minneapolis, University College of London [London] (UCL), University College London Hospitals (UCLH), Universidade Federal Rural do Rio de Janeiro (UFRRJ), Nihon University, Aarhus University [Aarhus], National University of Singapore (NUS), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Ubon Ratchathani University, and Medical Informatics
Subjects: medicine.medical_specialty, Asia, Population, diabetes & endocrinology, 030209 endocrinology & metabolism, Global Health, 03 medical and health sciences, 0302 clinical medicine, Health care, Epidemiology, medicine, Humans, 030212 general & internal medicine, education, Aged, Retrospective Studies, Hip fracture, education.field_of_study, business.industry, Hip Fractures, Public health, Incidence (epidemiology), Incidence, public health, Retrospective cohort study, General Medicine, Middle Aged, South America, medicine.disease, calcium & bone, 3. Good health, Europe, Systematic review, Medicine, epidemiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Demography
Abstract: IntroductionHip fractures are associated with a high burden of morbidity and mortality. Globally, there is wide variation in the incidence of hip fracture in people aged 50 years and older. Longitudinal and cross-geographical comparisons of health data can provide insights on aetiology, risk factors, and healthcare practices. However, systematic reviews of studies that use different methods and study periods do not permit direct comparison across geographical regions. Thus, the objective of this study is to investigate global secular trends in hip fracture incidence, mortality and use of postfracture pharmacological treatment across Asia, Oceania, North and South America, and Western and Northern Europe using a unified methodology applied to health records.Methods and analysisThis retrospective cohort study will use a common protocol and an analytical common data model approach to examine incidence of hip fracture across population-based databases in different geographical regions and healthcare settings. The study period will be from 2005 to 2018 subject to data availability in study sites. Patients aged 50 years and older and hospitalised due to hip fracture during the study period will be included. The primary outcome will be expressed as the annual incidence of hip fracture. Secondary outcomes will be the pharmacological treatment rate and mortality within 12 months following initial hip fracture by year. For the primary outcome, crude and standardised incidence of hip fracture will be reported. Linear regression will be used to test for time trends in the annual incidence. For secondary outcomes, the crude mortality and standardised mortality incidence will be reported.Ethics and disseminationEach participating site will follow the relevant local ethics and regulatory frameworks for study approval. The results of the study will be submitted for peer-reviewed scientific publications and presented at scientific conferences.
Published: 2021
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26. Mind the gap: from neurons to networks to outcomes in multiple sclerosis

Author: Chard, D. T., Alahmadi, A. A. S., Audoin, B., Charalambous, T., Enzinger, C., Hulst, H. E., Rocca, M. A., Rovira, A., Sastre-Garriga, J., Schoonheim, M. M., Tijms, B., Tur, C., Gandini Wheeler-Kingshott, C. A. M., Wink, A. M., Ciccarelli, O., Barkhof, F., De Stefano, N., Filippi, M., Frederiksen, J. L., Gasperini, C., Kappos, L., Palace, J., Yousry, T., Vrenken, H., University College of London [London] (UCL), Department of Diagnostic Radiology, Faculty of Applied Medical Science, King Abdulaziz University (KAU), Jeddah, Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - APHM] (CEMEREM), Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), AP-HM, CHU Timone, Pole de Neurosciences Cliniques, Department of Neurology, Marseille, France., Department of Neurology, Research Unit for Neuronal Repair and Plasticity, Medical University of Graz, Graz, Department of Radiology, Division of Neuroradiology, Vascular and Interventional Radiology, Medical University of Graz, Graz, Department of Anatomy and Neurosciences, MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Neuroimaging Research Unit and Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Universitat Autònoma de Barcelona (UAB), Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Department of Neurology, Luton and Dunstable University Hospital, Luton, Università degli Studi di Pavia = University of Pavia (UNIPV), Brain MRI 3T Research Center, IRCCS Mondino Foundation, Pavia, Department of Radiology & Nuclear Medicine, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, Faculty of Brain Sciences, University College London, London, National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre, London, Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - AP-HM] (CEMEREM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)- Hôpital de la Timone [CHU - APHM] (TIMONE), Section of Neuroradiology, Department of Radiology Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Servei de Neurologia/Neuroimmunologia, Multiple Sclerosis Centre of Catalonia (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Institutes of Neurology and Healthcare Engineering, University College London, London, Chard, Declan T, Alahmadi, Adnan A S, Audoin, Bertrand, Charalambous, Thali, Enzinger, Christian, Hulst, Hanneke E, Rocca, Maria A, Rovira, Àlex, Sastre-Garriga, Jaume, Schoonheim, Menno M, Tijms, Betty, Tur, Carmen, Gandini Wheeler-Kingshott, Claudia A M, Wink, Alle Meije, Ciccarelli, Olga, Barkhof, Frederik, MAGNIMS Study, Group, and Filippi, Massimo
Subjects: Multiple Sclerosis, Grey matter, Network topology, 030218 nuclear medicine & medical imaging, White matter, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Alzheimer Disease, medicine, Humans, Default mode network, ComputingMilieux_MISCELLANEOUS, Inflammation, Neurons, Artificial neural network, business.industry, Multiple sclerosis, [SCCO.NEUR]Cognitive science/Neuroscience, Brain, medicine.disease, medicine.anatomical_structure, Neurology (clinical), Disconnection, Alzheimer's disease, Nerve Net, business, Neuroscience, 030217 neurology & neurosurgery
Abstract: MRI studies have provided valuable insights into the structure and function of neural networks, particularly in health and in classical neurodegenerative conditions such as Alzheimer disease. However, such work is also highly relevant in other diseases of the CNS, including multiple sclerosis (MS). In this Review, we consider the effects of MS pathology on brain networks, as assessed using MRI, and how these changes to brain networks translate into clinical impairments. We also discuss how this knowledge can inform the targeting of MS treatments and the potential future directions for research in this area. Studying MS is challenging as its pathology involves neurodegenerative and focal inflammatory elements, both of which could disrupt neural networks. The disruption of white matter tracts in MS is reflected in changes in network efficiency, an increasingly random grey matter network topology, relative cortical disconnection, and both increases and decreases in connectivity centred around hubs such as the thalamus and the default mode network. The results of initial longitudinal studies suggest that these changes evolve rather than simply increase over time and are linked with clinical features. Studies have also identified a potential role for treatments that functionally modify neural networks as opposed to altering their structure.
Published: 2021
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27. A targeted ultra performance liquid chromatography – Tandem mass spectrometric assay for tyrosine and metabolites in urine and plasma: Application to the effects of antibiotics on mice

Author: Dumas, Marc-Emmanuel, Letertre, Marine, Myridakis, Antonis, Whiley, Luke, Camuzeaux, Stéphane, Lewis, Matthew, Chappell, Katie, Thaikkatil, Annie, Nicholson, Jeremy, Swann, Jonathan, Wilson, Ian, Letertre, Marine P.M., Division of Computational and Systems Medicine, Imperial College London, London, SW7 2AZ, UK, Imperial College London - National Heart and Lung Institute, Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Chimiques de Rennes (ISCR), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Imperial College London, Institute for Women's Health [London], University College London Hospitals (UCLH), Department of Surgery and Cancer [Londres, Royaume-Uni], Biomolecular Medicine, Division of Computational and Systems Medicine, Imperial College London, London, SW7 2AZ, UK., Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Electrospray, Clinical Biochemistry, Urine, 030226 pharmacology & pharmacy, 01 natural sciences, Biochemistry, High-performance liquid chromatography, Analytical Chemistry, MESH: Tyrosine, MESH: Linear Models, Cresols, Mice, chemistry.chemical_compound, 0302 clinical medicine, Limit of Detection, Tandem Mass Spectrometry, Liquid chromatography–mass spectrometry, Metabolites, MESH: Animals, Tyrosine, Chromatography, High Pressure Liquid, Dansyl Compounds, Mice, Inbred BALB C, Dansyl chloride, General Medicine, Anti-Bacterial Agents, MESH: Reproducibility of Results, MESH: Cresols, Female, Glucuronide, P-cresol conjugates, MESH: Mice, Inbred BALB C, MESH: Limit of Detection, MESH: Gastrointestinal Microbiome, Tyrosinemia, 03 medical and health sciences, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Quantification, MESH: Anti-Bacterial Agents, Biofluids, medicine, Animals, MESH: Chromatography, High Pressure Liquid, MESH: Mice, MESH: Dansyl Compounds, Chromatography, 010401 analytical chemistry, Reproducibility of Results, MESH: Tandem Mass Spectrometry, Cell Biology, medicine.disease, Gastrointestinal Microbiome, 0104 chemical sciences, chemistry, Linear Models, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Tyrosine plays a key role in mammalian biochemistry and defects in its metabolism (e.g., tyrosinemia, alkaptonuria etc.) have significant adverse consequences for those affected if left untreated. In addition, gut bacterially-derived p-cresol and its metabolites are of interest as a result of various effects on host xenobiotic metabolism. A fit-for-purpose quantitative ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay was developed to target and quantify tyrosine and eleven metabolites in urine and plasma. Dansylation, using dansyl chloride, was used to improve chromatographic and mass spectral properties for tyrosine and nine phenolic metabolites, with detection using positive electrospray ionisation (ESI). The sulfate and glucuronide conjugates of p-cresol, where the phenol group was blocked, were quantified intact, using negative ESI via polarity switching during the same run. Sample preparation for urine and plasma involved deproteinization by solvent precipitation (of acetonitrile:isopropyl alcohol (1:1 v/v)) followed by in situ dansylation in 96 well plates. To minimize sample and solvent usage, and maximize sensitivity, analysis was performed using microbore reversed-phase gradient UPLC on a C8 phase with a 7.5 min. cycle time. The coefficients of variation obtained were
Published: 2021
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28. Vessel-CAPTCHA: an efficient learning framework for vessel annotation and segmentation

Author: Dang, Vien Ngoc, Galati, Francesco, Cortese, Rosa, Di Giacomo, Giuseppe, Marconetto, Viola, Mathur, Prateek, Lekadir, Karim, Lorenzi, Marco, Prados, Ferran, Zuluaga, Maria A., Eurecom [Sophia Antipolis], University College of London [London] (UCL), Politecnico di Torino = Polytechnic of Turin (Polito), Departament de Tecnologies de la Informació i les Comunicacions [Barcelona] (ETIC / UPF), Universitat Pompeu Fabra [Barcelona] (UPF), University College London Hospitals (UCLH), and ANR-19-P3IA-0002,3IA@cote d'azur,3IA Côte d'Azur(2019)
Subjects: FOS: Computer and information sciences, Computer Vision and Pattern Recognition (cs.CV), Image Processing, education, Cerebrovascular tree, Deep learning, Efficient annotation, Segmentation, Weak supervised learning, ComputingMethodologies_IMAGEPROCESSINGANDCOMPUTERVISION, Computer Science - Computer Vision and Pattern Recognition, [INFO.INFO-CV]Computer Science [cs]/Computer Vision and Pattern Recognition [cs.CV], Processament digital d'imatges, Diagnòstic per la imatge, Computer-Assisted, Aprenentatge automàtic, Machine learning, Humans, Image Processing, Computer-Assisted, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Diagnostic imaging, Digital image processing
Abstract: International audience; Deep learning techniques for 3D brain vessel image segmentation have not been as successful as in the segmentation of other organs and tissues. This can be explained by two factors. First, deep learning techniques tend to show poor performances at the segmentation of relatively small objects compared to the size of the full image. Second, due to the complexity of vascular trees and the small size of vessels, it is challenging to obtain the amount of annotated training data typically needed by deep learning methods. To address these problems, we propose a novel annotation-efficient deep learning vessel segmentation framework. The framework avoids pixel-wise annotations, only requiring weak patch-level labels to discriminate between vessel and non-vessel 2D patches in the training set, in a setup similar to the CAPTCHAs used to differentiate humans from bots in web applications. The user-provided weak annotations are used for two tasks: 1) to synthesize pixel-wise pseudo-labels for vessels and background in each patch, which are used to train a segmentation network, and 2) to train a classifier network. The classifier network allows to generate additional weak patch labels, further reducing the annotation burden, and it acts as a second opinion for poor quality images. We use this framework for the segmentation of the cerebrovascular tree in Time-of-Flight angiography (TOF) and Susceptibility-Weighted Images (SWI). The results show that the framework achieves state-of-the-art accuracy, while reducing the annotation time by 77% w.r.t. learning-based segmentation methods using pixel-wise labels for training.
Published: 2021

29. Influence of COVID-19 pandemic on decisions for the management of people with inflammatory rheumatic and musculoskeletal diseases: a survey among EULAR countries

Author: Christian Dejaco, Johannes W. J. Bijlsma, Pedro Machado, Frank Buttgereit, Tanja Stamm, Francisca Sivera, Alessia Alunno, Ivan Padjen, Axel Finckh, Bernard Combe, Annelies Boonen, RS: CAPHRI - R3 - Functioning, Participating and Rehabilitation, Interne Geneeskunde, MUMC+: MA Reumatologie (9), Medical University Graz, Hospital of Brunico [Brunico], Università degli Studi di Perugia (UNIPG), University Medical Center [Utrecht], Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Service de Rhumatologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Hôpitaux Universitaires de Genève (HUG), University College of London [London] (UCL), University College London Hospitals (UCLH), University of Zagreb, University Hospital Centre Zagreb, Partenaires INRAE, Universidad Miguel Hernández [Elche] (UMH), Hospital General de Elda [Elda], Medizinische Universität Wien = Medical University of Vienna, and Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]
Subjects: medicine.medical_specialty, rheumatoid, Epidemiology, Autoimmune diseases, Immunology, Disease, RECOMMENDATIONS, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Tocilizumab, Rheumatology, Rheumatoid, Internal medicine, Pandemic, Health services research, Immunology and Allergy, Medicine, autoimmune diseases, 030212 general & internal medicine, Screening procedures, ddc:616, 030203 arthritis & rheumatology, Remote Consultation, epidemiology, arthritis, health services research, business.industry, Arthritis, 3. Good health, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, chemistry, Family medicine, CYTOKINE STORM, business
Abstract: ObjectivesTo investigate how the first wave of COVID-19 pandemic influenced decisions of rheumatologists and health professionals in rheumatology regarding the management of patients with inflammatory rheumatic and musculoskeletal diseases (RMDs).MethodsAn English-language questionnaire was developed by a EULAR working group and distributed via national rheumatology societies of EULAR countries, EMEUNET and individual working group members. Responses were collected using an online survey tool. Descriptive statistics were calculated.ResultsWe analysed 1286 responses from 35/45 EULAR countries. Due to containment measures, 82% of respondents indicated cancellation/postponement of face-to-face visits of new patients (84% of them offering remote consultation) and 91% of follow-up visits (96% with remote consultation). The majority of respondents (58%) perceived that the interval between symptom onset and first rheumatological consultations was longer during containment restrictions than before. Treatment decisions were frequently postponed (34%), and the majority (74%) of respondents stated that it was less likely to start a biological disease modifying anti-rheumatic drug (DMARD)/targeted synthetic DMARD during the pandemic, mainly because of patients’ fear, limited availability of screening procedures and decreased availability of rheumatological services. Use of (hydroxy)chloroquine (HCQ) and tocilizumab (TCZ) for the COVID-19 indication was reported by 47% and 42% of respondents, respectively, leading to a shortage of these drugs for RMDs indications according to 49% and 14% of respondents, respectively.ConclusionMeasures related to containment of COVID-19 pandemic led to a perceived delay between symptom onset and a first rheumatological visit, postponement of treatment decisions, and shortage of HCQ and TCZ, thereby negatively impacting early treatment and treat-to-target strategies.
Published: 2021
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30. The EHA research roadmap

Author: Astrid van Hylckama Vlieg, Pierre Morange, Marco Cattaneo, Isabella Garagiola, Tom van der Poll, Sabine Eichinger, David-Alexandre Trégouët, Paul A. Kyrle, Mathilde Fretigny, Flora Peyvandi, José A. Páramo, Wolfram Ruf, Antoine Rauch, Marcel Levi, Medizinische Universität Wien = Medical University of Vienna, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Università degli Studi di Milano [Milano] (UNIMI), Hospices Civils de Lyon (HCL), CHU Lille, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), Université de Lille, Leiden University Medical Center (LUMC), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), University Medical Center of the Johannes Gutenberg-University Mainz, University of Amsterdam [Amsterdam] (UvA), University College London Hospitals (UCLH), Clínica Universidad de Navarra [Pamplona], Università degli Studi di Milano = University of Milan (UNIMI), Universiteit Leiden, and Admin, Oskar
Subjects: medicine.medical_specialty, medicine.medical_treatment, Platelet disorder, Clinical science, Hematopoietic stem cell transplantation, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Diseases of the blood and blood-forming organs, Intensive care medicine, 030304 developmental biology, 0303 health sciences, Hematology, business.industry, Transfusion medicine, Hemostatic Disorders, 3. Good health, Blood Disorder, European policy, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Perspective, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, RC633-647.5, business
Abstract: International audience; In 2016, the European Hematology Association (EHA) published the EHA Roadmap for European Hematology Research(1) aiming to highlight achievements in the diagnostics and treatment of blood disorders, and to better inform European policy makers and other stakeholders about the urgent clinical and scientific needs and priorities in the field of hematology. Each section was coordinated by 1-2 section editors who were leading international experts in the field. In the 5 years that have followed, advances in the field of hematology have been plentiful. As such, EHA is pleased to present an updated Research Roadmap, now including 11 sections, each of which will be published separately. The updated EHA Research Roadmap identifies the most urgent priorities in hematology research and clinical science, therefore supporting a more informed, focused, and ideally funded future for European hematology research. The 11 EHA Research Roadmap sections include Normal Hematopoiesis; Malignant Lymphoid Diseases; Malignant Myeloid Diseases; Anemias and Related Diseases; Platelet Disorders; Blood Coagulation and Hemostatic Disorders; Transfusion Medicine; Infections in Hematology; Hematopoietic Stem Cell Transplantation; CAR-T and Other Cell-based Immune Therapies; and Gene Therapy.
Published: 2021
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31. Long-Term Efficacy and Safety of the Long-Acting Complement C5 Inhibitor Ravulizumab for the Treatment of Atypical Hemolytic Uremic Syndrome in Adults

Author: Thomas Barbour, Marie Scully, Gema Ariceta, Spero Cataland, Katherine Garlo, Nils Heyne, Yosu Luque, Jan Menne, Yoshitaka Miyakawa, Sung-Soo Yoon, David Kavanagh, Sunil Babu, Nilufer Broeders, Nicole Lietar, Fiona Brown, Philip Campbell, Josep M. Campistol, Paramit Chowdhury, Theo Kasimatis, Lino Cirami, Leonardo Caroti, Guilia Antognoli, Yahsou Delmas, Vladimir Dobronravov, Anja Gaeckler, Cyril Garrouste, Gregory Greenwood, Siân Griffin, Chiu-Ching Huang, I-Ru Chen, Susan Huang, Jin Seok Kim, Gaetano La Manna, Moglie Le Quintrec, Guillaume Jeantet, Iino Fumie, Eric Rondeau, Hermann Haller, Johan Morelle, Eric Goffin, Anja Muhlfeld, Shashi Nagaraj, Gowthami Arepally, Doyeun Oh, Masayoshi Okumi, Manuel Praga Terente, Francois Provot, Ulf Schönermarck, Michael Fischereder, Natalia Ramos Terrada, Barbara Seitz-Polski, Guillaume Favre, Sonia Boyer-Suavet, Maria Vinogradova, Tatiana Kirsanova, Edwin K.S. Wong, Barbour T., Scully M., Ariceta G., Cataland S., Garlo K., Heyne N., Luque Y., Menne J., Miyakawa Y., Yoon S.-S., Kavanagh D., Babu S., Broeders N., Lietar N., Brown F., Campbell P., Campistol J.M., Chowdhury P., Kasimatis T., Cirami L., Caroti L., Antognoli G., Delmas Y., Dobronravov V., Gaeckler A., Garrouste C., Greenwood G., Griffin S., Huang C.-C., Chen I.-R., Huang S., Kim J.S., La Manna G., Le Quintrec M., Jeantet G., Fumie I., Rondeau E., Haller H., Morelle J., Goffin E., Muhlfeld A., Nagaraj S., Arepally G., Oh D., Okumi M., Terente M.P., Provot F., Schonermarck U., Fischereder M., Terrada N.R., Seitz-Polski B., Favre G., Boyer-Suavet S., Vinogradova M., Kirsanova T., Wong E.K.S., Institut Català de la Salut, [Barbour T] Kidney Care, The Royal Melbourne Hospital, Melbourne, Australia. [Scully M] Department of Haematology, University College London Hospitals, London, UK. [Ariceta G] Servei de Nefrologia Pediàtrica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Cataland S] Division of Hematology, The Ohio State University Medical Center, Columbus, Ohio, USA. [Garlo K] Clinical Development, Alexion Pharmaceuticals, Inc., Boston, Massachusetts, USA. [Heyne N] Section of Nephrology and Hypertension, Tübingen University Hospital, Tübingen, Germany, Vall d'Hebron Barcelona Hospital Campus, UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - (SLuc) Service de néphrologie, The Royal Melbourne Hospital, University College London Hospitals (UCLH), Vall d'Hebron University Hospital [Barcelona], Ohio State University [Columbus] (OSU), Universitätsklinikum Tübingen - University Hospital of Tübingen, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Seoul National University Hospital, and Newcastle University [Newcastle]
Subjects: medicine.medical_specialty, Thrombotic microangiopathy, [SDV]Life Sciences [q-bio], Hemic and Lymphatic Diseases::Hematologic Diseases::Anemia::Anemia, Hemolytic::Hemolytic-Uremic Syndrome::Hemic and Lymphatic Diseases::Hematologic Diseases::Atypical Hemolytic Uremic Syndrome [DISEASES], 030232 urology & nephrology, Renal function, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], 030204 cardiovascular system & hematology, Other subheadings::Other subheadings::/drug therapy [Other subheadings], 03 medical and health sciences, 0302 clinical medicine, afecciones patológicas, signos y síntomas::procesos patológicos::atributos de la enfermedad::enfermedades raras [ENFERMEDADES], Clinical Research, Internal medicine, Atypical hemolytic uremic syndrome, Medicine, complement, Adverse effect, Complement component 5, business.industry, Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Rare Diseases [DISEASES], atypical hemolytic uremic syndrome, Acute kidney injury, diagnóstico::pronóstico::resultado del tratamiento [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], medicine.disease, Diagnosis::Prognosis::Treatment Outcome [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], ravulizumab, Diseases of the genitourinary system. Urology, 3. Good health, enfermedades hematológicas y linfáticas::enfermedades hematológicas::anemia::anemia hemolítica::síndrome hemolítico-urémico::enfermedades hematológicas y linfáticas::enfermedades hematológicas::síndrome hemolítico urémico atípico [ENFERMEDADES], kidney failure, thrombotic microangiopathy, Clinical trial, Nephrology, Avaluació de resultats (Assistència sanitària), hemolytic uremic syndrome, RC870-923, Síndrome hemolíticourèmica - Tractament, Malalties rares, business, Kidney disease
Abstract: Hemolytic uremic syndrome; Kidney failure; Ravulizumab Síndrome hemolítico urémico; Insuficiencia renal; Ravulizumab Síndrome hemolític urèmic; Insuficiència renal; Ravulizumab Introduction Atypical hemolytic uremic syndrome (aHUS) is a rare, complex, multisystem disease of dysregulated complement activity, characterized by progressive thrombotic microangiopathy (TMA), acute kidney injury, and multiorgan dysfunction, which often progresses to chronic kidney disease. Results from the prospective clinical trial of ravulizumab (NCT02949128) reveal rapid resolution of TMA in patients with aHUS, with sustained efficacy and safety in a 26-week initial evaluation period. Methods The aim of this analysis was to characterize the long-term efficacy and the safety profile of ravulizumab in adults with aHUS who had completed the initial evaluation period of the trial. Complete TMA response, hematologic and kidney functions, and safety were evaluated for all patients available for follow-up in the extension period (median follow-up: 76.7 weeks; range: 0.6–118.3). This trial included a total of 58 patients, 49 of whom entered the extension period. Results A total of 4 additional patients achieved complete TMA response during the follow-up period. Normalization of platelet count, serum lactate dehydrogenase (LDH), and hemoglobin observed in the 26-week initial evaluation period was sustained until the last available follow-up, as were the improvements in the estimated glomerular filtration rate (eGFR) and patient quality of life. All efficacy endpoints were correlated with the sustained inhibition of complement C5. Most adverse events (AEs) occurred early during the initial evaluation period and decreased substantially during the extension period. No patient developed a meningococcal infection or died during the extension period. Conclusion This analysis reveals that ravulizumab administered every 8 weeks is efficacious with an acceptable safety profile for the long-term treatment of adults with aHUS and provides additional clinical benefit beyond 6 months of treatment.
Published: 2021
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32. Representing the metabolome with high fidelity: range and response as quality control factors in LC-MS-based global profiling

Author: Caroline Sands, Chioma Izzi-Engbeaya, Elena Chekmeneva, Matthew R. Lewis, Stephane Camuzeaux, Gonçalo D S Correia, Waljit S. Dhillo, Zoltan Takats, María Gómez-Romero, Imperial College Healthcare NHS Trust- BRC Funding, Medical Research Council, Imperial College London, Institute for Women's Health [London], University College London Hospitals (UCLH), Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 (PRISM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), INSERM, Université de Lille, and Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Subjects: Quality Control, Analyte, [SDV]Life Sciences [q-bio], 010402 general chemistry, computer.software_genre, 01 natural sciences, Mass Spectrometry, Analytical Chemistry, Metabolomics, 0399 Other Chemical Sciences, Metabolome, Complex data type, Profiling (computer programming), Chemistry, 010401 analytical chemistry, 0104 chemical sciences, Data set, Feature (computer vision), Data quality, Data mining, Transcriptome, computer, 0301 Analytical Chemistry, Chromatography, Liquid
Abstract: International audience; Liquid chromatography-mass spectrometry (LC-MS) is a powerful and widely used technique for measuring the abundance of chemical species in living systems. Its sensitivity, analytical specificity, and direct applicability to biofluids and tissue extracts impart great promise for the discovery and mechanistic characterization of biomarker panels for disease detection, health monitoring, patient stratification, and treatment personalization. Global metabolic profiling applications yield complex data sets consisting of multiple feature measurements for each chemical species observed. While this multiplicity can be useful in deriving enhanced analytical specificity and chemical identities from LC-MS data, data set inflation and quantitative imprecision among related features is problematic for statistical analyses and interpretation. This Perspective provides a critical evaluation of global profiling data fidelity with respect to measurement linearity and the quantitative response variation observed among components of the spectra. These elements of data quality are widely overlooked in untargeted metabolomics yet essential for the generation of data that accurately reflect the metabolome. Advanced feature filtering informed by linear range estimation and analyte response factor assessment is advocated as an attainable means of controlling LC-MS data quality in global profiling studies and exemplified herein at both the feature and data set level.
Published: 2020
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33. Clinicogenomic factors of biotherapy immunogenicity in autoimmune disease: A prospective multicohort study of the ABIRISK consortium

Author: Caroline Trang, Salima Hacein-Bey Abina, Malin Ryner, Florian Deisenhammer, Manuel Comabella, Abiba Doukani, Philippe Broët, Anna Fogdell-Hahn, Julianne Duhaze, Hans-Peter Hartung, Clemens Warnke, Natacha Szely, Delphine Bachelet, Alessandra Vultaggio, Bernd C. Kieseier, Sebastian Spindeldreher, Olivier Brocq, Poul Erik Hyldgaard-Jensen, Michael Auer, Marc Pallardy, Matthieu Allez, Mary Birchler, Tom W J Huizinga, Yehuda Chowers, Yoram Bouhnik, Dorothea Buck-Martin, Elizabeth C. Jury, Amy Loercher, Dan Sikkema, Aude Gleizes, Tobias Derfuss, Jessica J Manson, Guillaume Cadiot, Claudia Sievers, Michael Khalil, Naoimh Donnellan, Raija L.P. Lindberg, Agnès Hincelin Mery, Badreddine Mohand Oumoussa, Enrico Maggi, Martin Soubrier, Kathleen Ingenhoven, Orhan Aktas, Sophie Tourdot, Xavier Montalban, Maria Nachury, Niek de Vries, Timothy P. Hickling, Christophe Richez, Bernhard Hemmer, Franck Carbonnel, Finn Sellebjerg, Jérôme Avouac, Petra Nytrova, Xavier Mariette, Anna Lauren, Signe Hässler, Pierre Dönnes, Eva Havrdova, Michael Guger, Claudia Mauri, BRUNEL, Nadège, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut de médecine et d'épidémiologie appliquée [AP-HP Hôpital Bichat-Claude Bernard] (IMEA), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Sainte Justine [Montréal], Université Paris-Saclay, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Université Paris Cité (UPCité), GlaxoSmithKline, Glaxo Smith Kline, Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Princesse Grace [Monaco], Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Hôpital universitaire Robert Debré [Reims], University of Haifa [Haifa], Universitat Autònoma de Barcelona (UAB), University Hospital Basel [Basel], VU University Medical Center [Amsterdam], Royal Berkshire Hospital, Plateforme Post-génomique de la Pitié-Salpêtrière (PASS-P3S), Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Kepler University Hospital, University Hospital Düsseldorf, Charles University [Prague] (CU), Leiden University Medical Center (LUMC), Rigshospitalet [Copenhagen], Copenhagen University Hospital, University College of London [London] (UCL), Karl-Franzens-Universität Graz, Malmö Högskola = Malmö University, University of Basel (Unibas), Università degli Studi di Firenze = University of Florence (UniFI), University College London Hospitals (UCLH), Service des Maladies de l'Appareil Digestif et de la Nutrition [CHRU Lille], Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU de Bordeaux Pellegrin [Bordeaux], Karolinska Institutet [Stockholm], CHU Clermont-Ferrand, Université de Florence, Fachhochschule Köln, University of Skövde [Sweden], Pfizer, SANOFI Recherche, Hopital Saint-Louis [AP-HP] (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Chimie du CNRS (INC)-Université de Paris (UP)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Dusseldorf, Innsbruck Medical University [Austria] (IMU), Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Karl-Franzens-Universität [Graz, Autriche], Malmø University, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), University of Graz, AII - Inflammatory diseases, and Clinical Immunology and Rheumatology
Subjects: Male, Physiology, [SDV]Life Sciences [q-bio], Single Nucleotide Polymorphisms, Autoimmune Diseases/drug therapy, Biological Therapy/methods, Arthritis, 030204 cardiovascular system & hematology, Biochemistry, Inflammatory bowel disease, Etanercept, Arthritis, Rheumatoid, Cohort Studies, chemistry.chemical_compound, Medical Conditions, 0302 clinical medicine, Crohn Disease, Antibiotics, Immune Physiology, Medicine and Health Sciences, Prospective Studies, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Immune System Proteins, Antimicrobials, Drugs, Neurodegenerative Diseases, General Medicine, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], Biological Therapy, Antibodies, Monoclonal, Humanized/therapeutic use, Neurology, Arthritis, Rheumatoid/drug therapy, Rheumatoid arthritis, Genome-Wide Association Study/methods, Medicine, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Rituximab, Immunosuppressive Agents, Interferon beta-1a, Research Article, medicine.drug, Adult, Multiple Sclerosis, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immunology, Rheumatoid Arthritis, Gastroenterology and Hepatology, Antibodies, Monoclonal, Humanized, Microbiology, Antibodies, HLA-DQ alpha-Chains, Autoimmune Diseases, 03 medical and health sciences, Tocilizumab, Rheumatology, Adalimumab/therapeutic use, Microbial Control, HLA-DQ alpha-Chains/genetics, Rituximab/therapeutic use, Genetics, medicine, Adalimumab, Humans, Antigens, Biological Products/immunology, Pharmacology, Biological Products, Interferon beta-1a/therapeutic use, business.industry, Inflammatory Bowel Disease, Biology and Life Sciences, Proteins, medicine.disease, Demyelinating Disorders, Infliximab, Minor allele frequency, Infliximab/therapeutic use, chemistry, Crohn Disease/drug therapy, Immunosuppressive Agents/therapeutic use, Multiple Sclerosis/drug therapy, Clinical Immunology, Colitis, Ulcerative, Clinical Medicine, Colitis, Ulcerative/drug therapy, business, Genome-Wide Association Study
Abstract: Background Biopharmaceutical products (BPs) are widely used to treat autoimmune diseases, but immunogenicity limits their efficacy for an important proportion of patients. Our knowledge of patient-related factors influencing the occurrence of antidrug antibodies (ADAs) is still limited. Methods and findings The European consortium ABIRISK (Anti-Biopharmaceutical Immunization: prediction and analysis of clinical relevance to minimize the RISK) conducted a clinical and genomic multicohort prospective study of 560 patients with multiple sclerosis (MS, n = 147), rheumatoid arthritis (RA, n = 229), Crohn’s disease (n = 148), or ulcerative colitis (n = 36) treated with 8 different biopharmaceuticals (etanercept, n = 84; infliximab, n = 101; adalimumab, n = 153; interferon [IFN]-beta-1a intramuscularly [IM], n = 38; IFN-beta-1a subcutaneously [SC], n = 68; IFN-beta-1b SC, n = 41; rituximab, n = 31; tocilizumab, n = 44) and followed during the first 12 months of therapy for time to ADA development. From the bioclinical data collected, we explored the relationships between patient-related factors and the occurrence of ADAs. Both baseline and time-dependent factors such as concomitant medications were analyzed using Cox proportional hazard regression models. Mean age and disease duration were 35.1 and 0.85 years, respectively, for MS; 54.2 and 3.17 years for RA; and 36.9 and 3.69 years for inflammatory bowel diseases (IBDs). In a multivariate Cox regression model including each of the clinical and genetic factors mentioned hereafter, among the clinical factors, immunosuppressants (adjusted hazard ratio [aHR] = 0.408 [95% confidence interval (CI) 0.253–0.657], p < 0.001) and antibiotics (aHR = 0.121 [0.0437–0.333], p < 0.0001) were independently negatively associated with time to ADA development, whereas infections during the study (aHR = 2.757 [1.616–4.704], p < 0.001) and tobacco smoking (aHR = 2.150 [1.319–3.503], p < 0.01) were positively associated. 351,824 Single-Nucleotide Polymorphisms (SNPs) and 38 imputed Human Leukocyte Antigen (HLA) alleles were analyzed through a genome-wide association study. We found that the HLA-DQA1*05 allele significantly increased the rate of immunogenicity (aHR = 3.9 [1.923–5.976], p < 0.0001 for the homozygotes). Among the 6 genetic variants selected at a 20% false discovery rate (FDR) threshold, the minor allele of rs10508884, which is situated in an intron of the CXCL12 gene, increased the rate of immunogenicity (aHR = 3.804 [2.139–6.764], p < 1 × 10−5 for patients homozygous for the minor allele) and was chosen for validation through a CXCL12 protein enzyme-linked immunosorbent assay (ELISA) on patient serum at baseline before therapy start. CXCL12 protein levels were higher for patients homozygous for the minor allele carrying higher ADA risk (mean: 2,693 pg/ml) than for the other genotypes (mean: 2,317 pg/ml; p = 0.014), and patients with CXCL12 levels above the median in serum were more prone to develop ADAs (aHR = 2.329 [1.106–4.90], p = 0.026). A limitation of the study is the lack of replication; therefore, other studies are required to confirm our findings. Conclusion In our study, we found that immunosuppressants and antibiotics were associated with decreased risk of ADA development, whereas tobacco smoking and infections during the study were associated with increased risk. We found that the HLA-DQA1*05 allele was associated with an increased rate of immunogenicity. Moreover, our results suggest a relationship between CXCL12 production and ADA development independent of the disease, which is consistent with its known function in affinity maturation of antibodies and plasma cell survival. Our findings may help physicians in the management of patients receiving biotherapies., In a multicohort prospective study of patients from 12 countries, Signe Hässler and colleagues investigate clinical and genetic factors associated with development of anti-biopharmaceutical drug antibodies in patients with autoimmune diseases., Author summary Why was this study done? Biopharmaceutical products such as monoclonal antibodies are widely used to treat autoimmune diseases. Biopharmaceutical products may induce the development of antidrug antibodies, which often lead to therapy failure. Patient-related factors that influence the development of antidrug antibodies need to be characterized. What did the researchers do and find? We set up a European multicohort prospective study on 4 autoimmune diseases (multiple sclerosis, rheumatoid arthritis, Crohn’s disease, and ulcerative colitis) treated with 8 different biopharmaceutical products. We collected demographic and clinical data and tested antidrug antibodies in longitudinal serum samples from 560 patients. For 457 patients who gave consent, we also collected genetic data. We identified antibiotics and immunosuppressants as negatively associated risk factors and heavy smoking, infections during the study, the HLA-DQA1*05 allele and a minor variant in the CXCL12 chemokine gene associated with increased protein expression as risk factors of antidrug antibody development. What do these findings mean? Our findings suggest that the combination of immunosuppressant and biopharmaceutical therapy could be associated with decreased risk of antidrug antibody occurrence, which has implications for rheumatoid arthritis and inflammatory bowel diseases, for which immunosuppressants are often, but not always, given together with biopharmaceuticals. Patients heterozygotes or homozygotes for the HLA-DQA1*05 allele may have an increased risk of antidrug antibody occurrence associated with biopharmaceutical therapy. The small study size warrants a validation through independent studies, in particular for the genetic findings.
Published: 2020
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34. In utero exposure to Azathioprine in autoimmune disease. Where do we stand?

Author: Rebecca Bromley, Laura Damian, Marianne Rivière, Hilde Kelchtermans, Katrien Devreese, Yehuda Shoenfeld, Daniel Henrion, Enrique Esteve-Valverde, Patrick Martin Mattera, Laurent Loufrani, Cristina Belizna, Alexandre Levy, Sebastián Udry, Anne-Laure Guihot, Angela Tincani, Jamilya Khizroeva, Taylor Pindi Sala, Rosario Lopez Pedrera, A. Djokovic, Milena Hasan, Nadia Bahi Buisson, Jaume Alijotas-Reig, Maria Orietta Borghi, Géraldine Gascoin, José Omar Latino, Jan Willem Cohen Tervaert, Pier Luigi Meroni, Hannah Cohen, Viktoria Bidsatze, Laurence Bernard, Cecilia Beatrice Chighizola, Johanna Gebhart, Francesca Pregnolato, N. Stanisavljevic, Marie Briet, Mathilde Saiet, Elisabeth Elefant-Amoura, Pascale Peretti, Laurence Lagarce, Ljudmila Stojanovich, Ingrid Pabinger, Jose Rakotonjanahary, Isabelle Pellier, Alexander Makatsariya, Céline Fassot, Marie Noelle Ungeheuer, Laura Andreoli, Christian Muchardt, Jan Voswinkel, Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Clinical Immunology and Rheumatology Research Department Auxologico Institute, Milan, Italy., The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Ghent University Hospital, Vall d'Hebron University Hospital [Barcelona], Althaia Healthcare Network of Manresa, Barcelona, University College London Hospitals (UCLH), Clinique de l'Anjou [Angers], Recherches en Psychopathologie, nouveaux symptômes et lien social (EA 4050), Université de Poitiers-Université de Brest (UBO)-Université Catholique de l'Ouest (UCO)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), University of Angers, Angers Hospital, French Lupus and Other Autoimmune Disease Patients Association, Institut Pasteur [Paris], Régulation épigénétique - Epigenetic regulation, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Cytometrie et Biomarqueurs – Cytometry and Biomarkers (UTechS CB), Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources (ICAReB), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Laboratoire Recherches en psychopathologie et psychanalyse (RPPSY), Université Catholique de l'Ouest (UCO), Institut Pasteur [Paris] (IP), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Pediatrics, medicine.medical_specialty, Offspring, [SDV]Life Sciences [q-bio], Immunology, Population, Azathioprine, Autoimmune Diseases, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Genetic predisposition, Immunology and Allergy, Medicine, Humans, education, Prospective cohort study, Child, Female, Immunosuppressive Agents, Pregnancy Complications, Prenatal Exposure Delayed Effects, Retrospective Studies, 030203 arthritis & rheumatology, education.field_of_study, business.industry, Public health, Retrospective cohort study, medicine.disease, 3. Good health, 030211 gastroenterology & hepatology, business, medicine.drug
Abstract: International audience; Azathioprine (AZA), an oral immunosuppressant, is safe during pregnancy. Some reports suggested different impairments in the offspring of mothers with autoimmune diseases (AI) exposed in utero to AZA. These observations are available from retrospective studies or case reports. However, data with respect to the long-term safety in the antenatally exposed child are still lacking. The aim of this study is to summarize the current knowledge in this field and to focus on the need for a prospective study on this population. We performed a PubMed search using several search terms. The actual data show that although the risk of congenital anomalies in offspring, as well as the infertility risk, are similar to those found in general population, there is a higher incidence of prematurity, of lower weight at birth and an intra-uterine delay of development. There is also an increased risk of materno- fetal infections, especially cytomegalovirus infection. Some authors raise the interrogations about neurocognitive impairment. Even though the adverse outcomes might well be a consequence of maternal illness and disease activity, interest has been raised about a contribution of this drug. However, the interferences between the external agent (in utero exposure to AZA), with the host (child genetic susceptibility, immune system anomalies, emotional status), environment (public health, social context, availability of health care), economic, social, and behavioral conditions, cultural patterns, are complex and represent confounding factors. In conclusion, it is necessary to perform studies on the medium and long-term outcome of children born by mothers with autoimmune diseases, treated with AZA, in order to show the safety of AZA exposure. Only large-scale population studies with long-term follow-up will allow to formally conclude in this field
Published: 2020
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35. The Great Debate at ‘Immunotherapy Bridge’, Naples, December 5, 2019

Author: Carlo Bifulco, Sergio A. Quezada, Paolo A. Ascierto, Claus Garbe, Hussein Abdul-Hassan Tawbi, Giorgio Trinchieri, Igor Puzanov, Jennifer L. McQuade, Kunle Odunsi, John M. Timmerman, Chrystal M. Paulos, Lisa H. Butterfield, Hideho Okada, Jérôme Galon, Samir N Khleif, Unit of Melanoma Medical Oncology [Fondazione IRCCS Istituto Nazionale Tumori, Milan], Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], Providence Portland Medical Center, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Universitätsklinikum Tübingen - University Hospital of Tübingen, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Georgetown University Medical Center, The University of Texas M.D. Anderson Cancer Center [Houston], Roswell Park Cancer Institute [Buffalo], University of California [San Francisco] (UCSF), University of California, Hollings Cancer Center [Charleston], Medical University of South Carolina [Charleston] (MUSC), University College London Hospitals (UCLH), California State University [Los Angeles] (CAL STATE LA), and National Institutes of Health [Bethesda] (NIH)
Subjects: CTLA-4 antigen, 0301 basic medicine, Cancer Research, medicine.medical_treatment, Immunology, receptors, Meeting Report, History, 21st Century, 03 medical and health sciences, 0302 clinical medicine, Humans, Immunology and Allergy, Medicine, immunologic, Cell-mediated cytotoxicity, RC254-282, Pharmacology, business.industry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, CTLA-4 Antigen, Immunotherapy, 3. Good health, Clinical Practice, 030104 developmental biology, Oncology, chimeric antigen, 030220 oncology & carcinogenesis, cytotoxicity, Molecular Medicine, [SDV.IMM]Life Sciences [q-bio]/Immunology, Chimeric Antigen Receptor T-Cell Therapy, business
Abstract: International audience; As part of the 2019 Immunotherapy Bridge congress (December 4–5, Naples, Italy), the Great Debate session featured counterpoint views from leading experts on six topical issues in immunotherapy today. These were the use of chimeric antigen receptor T cell therapy in solid tumors, whether the Immunoscore should be more widely used in clinical practice, whether antibody-dependent cellular cytotoxicity is important in the mode of action of anticytotoxic T-lymphocyte-associated protein 4 antibodies, whether the brain is immunologically unique or just another organ, the role of microbiome versus nutrition in affecting responses to immunotherapy, and whether chemotherapy is immunostimulatory or immunosuppressive. Discussion of these important topics are summarized in this report.
Published: 2020
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36. Acceptability in the Older Population: The Importance of an Appropriate Tablet Size

Author: Yogini Jani, Patrick Leglise, Matthieu Piccoli, Vincent Boudy, Hugues Michelon, Aurélie Le Fur, Thibault Vallet, Mine Orlu, Fabrice Ruiz, Sandra Laribe-Caget, Fang Liu, ClinSearch, Hôpital Sainte Perine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), UCL School of Pharmacy, University College London Hospitals (UCLH), Hôpitaux Universitaires Henri-Mondor, Hôpital Rothschild [AP-HP], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], University of Hertfordshire [Hatfield] (UH), Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Institut de Chimie du CNRS (INC)-Université de Paris (UP)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), ORANGE, Colette, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Subjects: medicine.medical_specialty, medicine, Care homes, Pharmaceutical Science, lcsh:RS1-441, formulation, 02 engineering and technology, CAST (ClinSearch acceptability score test), [SDV.SP.PG] Life Sciences [q-bio]/Pharmaceutical sciences/Galenic pharmacology, DYSPHAGIA, 030226 pharmacology & pharmacy, size, Article, Older population, lcsh:Pharmacy and materia medica, 03 medical and health sciences, 0302 clinical medicine, Older patients, acceptability, otorhinolaryngologic diseases, SODF, business.industry, Swallowing Disorders, ADULTS, 021001 nanoscience & nanotechnology, Dysphagia, older population, 3. Good health, [SDV.SP.PG]Life Sciences [q-bio]/Pharmaceutical sciences/Galenic pharmacology, MEDICINES, Physical therapy, medicine.symptom, 0210 nano-technology, Older people, business
Abstract: Presenting many advantages, solid oral dosage forms (SODFs) are widely manufactured and frequently prescribed in older populations regardless of the specific characteristics of patients. Commonly, patients with dysphagia (swallowing disorders) experience difficulties taking SODFs, which may lead to non-adherence or misuse. SODF characteristics (e.g., size, shape, thickness) are likely to influence swallowability. Herein, we used the acceptability reference framework (the ClinSearch acceptability score test (CAST))&mdash, a 3D-map juxtaposing two acceptability profiles&mdash, to investigate the impact of tablet size on acceptability. We collected 938 observer reports on the tablet intake by patients &ge, 65 years in hospitals or care homes. As we might expect, tablets could be classified as accepted in older patients without dysphagia (n = 790), while not in those with swallowing disorders (n = 146). However, reducing the tablet size had a significant impact on acceptability in this subpopulation: tablets &lt, 6.5 mm appeared to be accepted by patients with swallowing disorders. Among the 309 distinct tablets assessed in this study, ranging in size from 4.7 to 21.5 mm, 83% are &ge, 6.5 mm and consequently may be poorly accepted by institutionalized older people and older inpatients suffering from dysphagia. This underlines the need to develop and prescribe medicines with the best adapted characteristics to reach an optimal acceptability in targeted users.
Published: 2020
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37. Coronavirus infections: Epidemiological, clinical and immunological features and hypotheses

Author: Franco Locatelli, Didier Raoult, Guido Kroemer, Alimuddin Zumla, Giuseppe Ippolito, Microbes évolution phylogénie et infections (MEPHI), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), University College of London [London] (UCL), University College London Hospitals (UCLH), IRCCS Ospedale Pediatrico Bambino Gesù [Roma], National Institute for Infectious Diseases 'Lazzaro Spallanzani', Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Plateforme de métabolomique, Direction de la recherche [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Cell Biology Platform [Villejuif], Institut Gustave Roussy (IGR), Pôle de Biologie [Paris], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Chinese Academy of Medical Sciences [Suzhou, Chine] (CAMS), Karolinska Institutet [Stockholm], Didier Roult is supported by the French Government under the « Investissements d’avenir » (Investments for the Future) program managed by the Agence Nationale de la Recherche (ANR, fr: National Agency for Research), (reference: Méditerranée Infection 10-IAHU-03). Alimuddin Zumla and Giuseppe Ippolito are co-principal investigators of the Pan-African Network on Emerging and Re-emerging Infections (PANDORA-ID-NET), funded by the European & Developing Countries Clinical Trials Partnership, supported under Horizon 2020. Sir Zumla is in receipt of a National Institutes of Health Research senior investigator award. Giuseppe Ippolito is supported by the Italian Ministry of Health (Ricerca Corrente Linea 1. GK is supported by the Ligue contre le Cancer (équipe labellisée), Agence National de la Recherche (ANR) – Projets blancs, ANR under the frame of E-Rare-2, the ERA-Net for Research on Rare Diseases, AMMICa US23/CNRS UMS3655, Association pour la recherche sur le cancer (ARC), Association 'Le Cancer du Sein, Parlons-en!', Cancéropôle Ile-de-France, Chancelerie des universités de Paris (Legs Poix), Fondation pour la Recherche Médicale (FRM), a donation by Elior, European Research Area Network on Cardiovascular Diseases (ERA-CVD, MINOTAUR), Gustave Roussy Odyssea, the European Union Horizon 2020 Project Oncobiome, Fondation Carrefour, High-end Foreign Expert Program in China (GDW20171100085), Institut National du Cancer (INCa), Inserm (HTE), Institut Universitaire de France, LeDucq Foundation, the LabEx Immuno-Oncology (ANR-18-IDEX-0001), the RHU Torino Lumière, the Seerave Foundation, the SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE), and the SIRIC Cancer Research and Personalized Medicine (CARPEM)., ANR-10-IAHU-0003,Méditerranée Infection,I.H.U. Méditerranée Infection(2010), Bodescot, Myriam, Instituts Hospitalo-Universitaires - I.H.U. Méditerranée Infection - - Méditerranée Infection2010 - ANR-10-IAHU-0003 - IAHU - VALID, Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), and École Pratique des Hautes Études (EPHE)
Subjects: Cancer Research, medicine.medical_specialty, Physiology, viruses, lcsh:Medicine, medicine.disease_cause, Biochemistry, Genetics and Molecular Biology (miscellaneous), Virus, immunology, 03 medical and health sciences, MERS-CoV, 0302 clinical medicine, Epidemiology, Pandemic, medicine, sARS-CoV-2, 030212 general & internal medicine, Intensive care medicine, lcsh:QH301-705.5, 030304 developmental biology, Coronavirus, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, 0303 health sciences, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Respiratory tract infections, business.industry, Public health, lcsh:R, Outbreak, virus diseases, COVID-19, SARS-CoV, 3. Good health, coronavirus, epidemiology, SARS-CoV-2, Editorial, lcsh:Biology (General), Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Preparedness, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Molecular Medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: International audience; Coronaviruses (CoVs) are a large family of enveloped, positive-strand RNA viruses. Four human CoVs (HCoVs), the non-severe acute respiratory syndrome (SARS)-like HCoVs (namely HCoV 229E, NL63, OC43, and HKU1), are globally endemic and account for a substantial fraction of upper respiratory tract infections. Non-SARS-like CoV can occasionally produce severe diseases in frail subjects but do not cause any major (fatal) epidemics. In contrast, SARS like CoVs (namely SARS-CoV and Middle-East respiratory syndrome coronavirus, MERS-CoV) can cause intense short-lived fatal outbreaks. The current epidemic caused by the highly contagious SARS-CoV-2 and its rapid spread globally is of major concern. There is scanty knowledge on the actual pandemic potential of this new SARS-like virus. It might be speculated that SARS-CoV-2 epidemic is grossly underdiagnosed and that the infection is silently spreading across the globe with two consequences: (i) clusters of severe infections among frail subjects could haphazardly occur linked to unrecognized index cases; (ii) the current epidemic could naturally fall into a low-level endemic phase when a significant number of subjects will have developed immunity. Understanding the role of paucisymptomatic subjects and stratifying patients according to the risk of developing severe clinical presentations is pivotal for implementing reasonable measures to contain the infection and to reduce its mortality. Whilst the future evolution of this epidemic remains unpredictable, classic public health strategies must follow rational patterns. The emergence of yet another global epidemic underscores the permanent challenges that infectious diseases pose and underscores the need for global cooperation and preparedness, even during inter-epidemic periods.
Published: 2020
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38. Prenatal diagnosis, imaging, and prognosis in Congenital Diaphragmatic Hernia

Author: Francesca Russo, Jan Deprest, Alexandra Benachi, Anne-Gaël Cordier, Centre de Référence Maladie Rare 'Syndromes neurologiques Paranéoplasiques', Hospices Civils de Lyon (HCL)-Hopital Neurologique, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Institute for Women's Health [London], and University College London Hospitals (UCLH)
Subjects: medicine.medical_specialty, Referral, Hypertension, Pulmonary, [SDV]Life Sciences [q-bio], Prenatal diagnosis, Congenital diaphragmatic hernia, Severity of Illness Index, Ultrasonography, Prenatal, 03 medical and health sciences, 0302 clinical medicine, Imaging, Three-Dimensional, Pregnancy, 030225 pediatrics, Prenatal Diagnosis, medicine, Humans, Lung, Genetic testing, Fetus, Comparative Genomic Hybridization, Fetal Therapies, 030219 obstetrics & reproductive medicine, medicine.diagnostic_test, Obstetrics, business.industry, Ultrasound, Obstetrics and Gynecology, Abortion, Induced, Organ Size, medicine.disease, Prognosis, Magnetic Resonance Imaging, 3. Good health, medicine.anatomical_structure, Liver, In utero, Pediatrics, Perinatology and Child Health, Amniocentesis, Female, business, Hernias, Diaphragmatic, Congenital
Abstract: Antenatal ultrasound screening identifies more than 60% of Congenital Diaphragmatic Hernia (CDH) cases and provides the opportunity for in utero referral to a tertiary care center for expert assessment and perinatal management. Prenatal assessment of fetuses with CDH has tremendously improved over the past ten years. The outcome may be predicted prenatally by medical imaging and advanced genetic testing. The combination of lung size and liver position determination by ultrasound measurements and MRI are widely accepted methods to stratify fetuses into groups that correlate not only with neonatal mortality but also with morbidity. Notwithstanding this, prediction of persistent pulmonary hypertension of the newborn still needs to be improved. ispartof: SEMINARS IN PERINATOLOGY vol:44 issue:1 ispartof: location:United States status: published
Published: 2020
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39. Acalabrutinib monotherapy in patients with Waldenström macroglobulinemia: a single-arm, multicentre, phase 2 study

Author: Priti Patel, Dih-Yih Chen, Olivier Tournilhac, Thérèse Aurran-Schleinitz, Raquel Izumi, Efstathios Kastritis, Sheeba K. Thomas, Ahmed Hamdy, Monique C. Minnema, Francesco Forconi, Helen McCarthy, Richard R. Furman, Pier Luigi Zinzani, Diana Mittag, Shirley D'Sa, Daniel Reif Greenwald, Marie José Kersten, Simon Rule, Sunil Iyengar, Harriet S. Walter, Jaimal Kothari, Roger G. Owen, Sun Ku Lee, Melanie M. Frigault, Helen Wei, Bruce D. Cheson, Department of Haematology, Derriford Hospital, University College London Hospitals (UCLH), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), University of Southampton, University of Amsterdam [Amsterdam] (UvA), L. and A. Seràgnoli Hospital, University of Bologna, National and Kapodistrian University of Athens (NKUA), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Lombardi Comprehensive Cancer Center, Acerta Pharma (Redwood City, CA), Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), CCA - Cancer Treatment and Quality of Life, AII - Cancer immunology, Clinical Haematology, Owen, Roger G, McCarthy, Helen, Rule, Simon, D'Sa, Shirley, Thomas, Sheeba K, Tournilhac, Olivier, Forconi, Francesco, Kersten, Marie José, Zinzani, Pier Luigi, Iyengar, Sunil, Kothari, Jaimal, Minnema, Monique C, Kastritis, Efstathio, Aurran-Schleinitz, Thérèse, Cheson, Bruce D, Walter, Harriet, Greenwald, Daniel, Chen, Dih-Yih, Frigault, Melanie M, Hamdy, Ahmed, Izumi, Raquel, Patel, Priti, Wei, Helen, Lee, Sun Ku, Mittag, Diana, and Furman, Richard R
Subjects: Male, medicine.medical_specialty, Neutropenia, Gastrointestinal Diseases, Pain, Phases of clinical research, Salvage therapy, Antineoplastic Agents, 03 medical and health sciences, 0302 clinical medicine, Recurrence, Chemoimmunotherapy, Lower respiratory tract infection, Internal medicine, Agammaglobulinaemia Tyrosine Kinase, Journal Article, Clinical endpoint, Humans, Medicine, Molecular Targeted Therapy, Adverse effect, Protein Kinase Inhibitors, Respiratory Tract Infections, ComputingMilieux_MISCELLANEOUS, Aged, Salvage Therapy, business.industry, Waldenstrom macroglobulinemia, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, medicine.disease, Neoplasm Proteins, 3. Good health, Treatment Outcome, Acalabrutinib, monotherapy, Waldenström macroglobulinemia, Pyrazines, 030220 oncology & carcinogenesis, Benzamides, Myeloid Differentiation Factor 88, Quality of Life, Female, Waldenstrom Macroglobulinemia, business, 030215 immunology
Abstract: Summary Background Chemoimmunotherapy is typically the standard of care for patients with Waldenstrom macroglobulinemia; however, infectious and hematologic toxic effects are problematic. Acalabrutinib is a selective, potent Bruton tyrosine-kinase inhibitor. The aim of this trial was to evaluate the activity and safety of acalabrutinib in patients with Waldenstrom macroglobulinemia. Methods This single-arm, multicentre, phase 2 trial was done in 19 European academic centres in France, Italy, Greece, the Netherlands, and the UK, and eight academic centres in the USA. Eligible patients were 18 years or older and had treatment naive (declined or not eligible for chemoimmunotherapy) or relapsed or refractory (at least one previous therapy) Waldenstrom macroglobulinemia that required treatment, an Eastern Cooperative Oncology Group performance status of 2 or less, and received no previous Bruton tyrosine-kinase inhibitor therapy. Patients received 100 mg oral acalabrutinib twice per day in 28-day cycles until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed overall response (at least a minor response) according to the 6th International Workshop for Waldenstrom Macroglobulinemia (IWWM) and the modified 3rd IWWM workshop criteria. The primary outcome and safety were assessed in all patients who received at least one dose of treatment. This study is registered with ClinicalTrials.gov , number NCT02180724 , and is ongoing, but no longer enrolling. Findings Between Sept 8, 2014, and Dec 24, 2015, 122 patients were assessed for eligibility, of which 106 (87%) patients were given acalabrutinib (14 were treatment naive and 92 had relapsed or refractory disease). With a median follow-up of 27·4 months (IQR 26·0–29·7), 13 (93% [95% CI 66–100]) of 14 treatment naive patients achieved an overall response and 86 (93% [86–98]) of 92 relapsed or refractory patients per both the modified 3rd and 6th IWWM criteria. Seven (50%) of 14 treatment naive patients and 23 (25%) of 92 relapsed or refractory patients discontinued treatment on study. Grade 3–4 adverse events occurring in more than 5% of patients were neutropenia (17 [16%] of 106 patients) and pneumonia (7 [7%]). Grade 3–4 atrial fibrillation occurred in one (1%) patient and grade 3–4 bleeding occurred in three (3%) patients. The most common serious adverse events were lower respiratory tract infection (n=7 [7%]), pneumonia (n=7 [7%]), pyrexia (n=4 [4%]), cellulitis (n=3 [3%]), fall (n=3 [3%]), and sepsis (n=3 [3%]). Pneumonia (n=5 [5%]) and lower respiratory tract infection (n=4 [4%]) were considered treatment related. One treatment-related death was reported (intracranial hematoma). Interpretation This study provides evidence that acalabrutinib is active as single-agent therapy with a manageable safety profile in patients with treatment-naive, or relapse or refractory Waldenstrom macroglobulinemia. Further studies are needed to establish its efficacy against current standard treatments and to investigate whether outcomes can be improved with combination therapies. Funding Acerta Pharma.
Published: 2020
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40. Lamin and the heart

Author: Gabriella Captur, Carolyn Y. Ho, James C. Moon, Antoine Muchir, Petros Syrris, William J. McKenna, Kevin Mills, Gisèle Bonne, Stephen J. Pettit, Perry M. Elliott, Eloisa Arbustini, Paul Gissen, Saidi A Mohiddin, Karim Wahbi, University College London Hospitals (UCLH), Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Centre de Recherche en Myologie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), University College of London [London] (UCL), Centre de référence des maladies rares neuromusculaires, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Queen Mary University of London (QMUL), Cambridge University Hospitals - NHS (CUH), University of Cambridge [UK] (CAM), Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Centre de recherche en Myologie – U974 SU-INSERM, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de référence des maladies rares neuromusculaires [CHU Pitié-Salpétriêre], 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), and Gestionnaire, HAL Sorbonne Université 5
Subjects: Cardiomyopathy, Dilated, 0301 basic medicine, [SDV.MHEP.AHA] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Pathology, medicine.medical_specialty, Heart disease, medicine.medical_treatment, 030204 cardiovascular system & hematology, Bioinformatics, medicine.disease_cause, LMNA, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], medicine, Humans, Intermediate filament, Heart transplantation, Mutation, integumentary system, business.industry, Disease Management, Dilated cardiomyopathy, Lamin Type A, medicine.disease, 3. Good health, Cardiac Imaging Techniques, 030104 developmental biology, Heart failure, Cardiology and Cardiovascular Medicine, business, Lamin
Abstract: Lamins A and C are intermediate filament nuclear envelope proteins encoded by theLMNAgene. Mutations inLMNAcause autosomal dominant severe heart disease, accounting for 10% of dilated cardiomyopathy (DCM). Characterised by progressive conduction system disease, arrhythmia and systolic impairment, lamin A/C heart disease is more malignant than other common DCMs due to high event rates even when the left ventricular impairment is mild. It has several phenotypic mimics, but overall it is likely to be an under-recognised cause of DCM. In certain clinical scenarios, particularly familial DCM with early conduction disease, the pretest probability of finding anLMNAmutation may be quite high.Recognising lamin A/C heart disease is important because implantable cardioverter defibrillators need to be implanted early. Promising oral drug therapies are within reach thanks to research into the mitogen-activated protein kinase (MAPK) and affiliated pathways. Personalised heart failure therapy may soon become feasible forLMNA, alongside personalised risk stratification, as variant-related differences in phenotype severity and clinical course are being steadily elucidated.Genotyping and family screening are clinically important both to confirm and to excludeLMNAmutations, but it is the three-pronged integration of such genetic information with functional data from in vivo cardiomyocyte mechanics, and pathological data from microscopy of the nuclear envelope, that is properly reshaping ourLMNAknowledge base, one variant at a time. This review explains the biology of lamin A/C heart disease (genetics, structure and function of lamins), clinical presentation (diagnostic pointers, electrocardiographic and imaging features), aspects of screening and management, including current uncertainties, and future directions.
Published: 2017
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41. Glioma staging with CEST asymmetry curves and amides/amines ratio

Author: Mancini, Laura, Casagranda, Stefano, Torrealdea, Francisco, Rega, Marilena, De Vita, Enrico, Lopez, Bruno, Brandner, Sebastian, Schmitt, Benjamin, Liebig, Patrick, Sanverdi, Eser, Golay, Xavier, Bisdas, Sotirios, Casagranda, Stefano, University College London Hospitals (UCLH), University College of London [London] (UCL), Olea Medical [La Ciotat], King‘s College London, and Siemens Healthcare
Subjects: [SDV.CAN] Life Sciences [q-bio]/Cancer, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, [INFO.INFO-IM] Computer Science [cs]/Medical Imaging, [SDV.CAN]Life Sciences [q-bio]/Cancer
Abstract: International audience; Gliomas are the most common primary brain tumour, whose staging depends on the IDH and 1p/19q status and is reflected in different prognoses and clinical management. CEST is a highly sensitive MRI technique detecting amide-and amine-containing mobile proteins. The CEST amides/amines ratio has been proposed as a measure of pH in stroke. We show that CEST amides/amines ratio is much more sensitive than separate amides and amines CEST in differentiating gliomas with the best prognosis (IDH-mutant 1p/19q-retained) from those with the worst prognosis (IDH-wildtype). The different shapes in CEST asymmetry spectra could also potentially help in glioma staging.
Published: 2020

42. Pathogenic variants in the DEAH-box RNA helicase DHX37 are a frequent cause of 46,XY gonadal dysgenesis and 46,XY testicular regression syndrome

Author: Tiphanie Merel, Matthieu Peycelon, Serge Nef, Daisylyn Senna Tan, Evgenia Globa, Rita Bertalan, Inas Mazen, John C. Achermann, Andy Greenfield, Romain Le Ru, Jean-Pierre Siffroi, Anne Jorgensen, Ken McElreavey, Ágnes Sallai, Brigitte Mignot, Ralf Jauch, Laetitia Martinerie, Raissa G. G. Kay, Gerard S. Conway, Joelle Bignon-Topalovic, Juliane Léger, Nick Warr, Denis Houzelstein, Federica Buonocore, Anu Bashamboo, Raja Brauner, Caroline Eozenou, Lionel Van Maldergem, Yuliya Shcherbak, Jean-Claude Carel, Génétique du Développement humain - Human developmental genetics, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Rigshospitalet [Copenhagen], Copenhagen University Hospital, Génétique Evolutive Humaine - Human Evolutionary Genetics, The University of Hong Kong (HKU), University College of London [London] (UCL), Medical Research Coucil Harwell [Oxford, UK] (MRC Harwell), MRC Harwell, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Robert Debré Paris, Hôpital Robert Debré, Indiana University - Purdue University Indianapolis (IUPUI), Indiana University System, National Research Centre [Cairo, Egypt], Semmelweis University [Budapest], Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Institute for Women's Health [London], University College London Hospitals (UCLH), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Université Paris Descartes - Paris 5 (UPD5), University of Geneva [Switzerland], A.B. is funded in part by a research grant from the European Society of Pediatric Endocrinology, and by the Agence Nationale de la Recherche (ANR), ANR-10-LABX-73 REVIVE and ANR-17-CE14-0038-01. J.C.A. is a Wellcome Trust Senior Research Fellow in Clinical Science (grant 098513/Z/12/Z) with support from the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust, University College London, and Great Ormond Street Hospital Children’s Charity. A.G. acknowledges support from the UK Medical Research Council through core funding at the Harwell Institute (MC_U142684167). RJ is supported by a Research Grants Council of Hong Kong General Research Fund (RGC/GRF) project number 17128918, a Health and Medical Research Fund (06174006) and Germany/Hong Kong Joint Research Scheme sponsored by the Research Grants Council of Hong Kong and the German Academic Exchange. This work is supported by the COST Action DSDnet BM130., The authors thank Eszter Regős and Tamás Micsik, Semmelweis University, Budapest, Hungary and Ewa Rajpert-De Meyts, Rigshospitalet, Copenhagen, Denmark for valuable comments on the study., ANR-10-LABX-0073,REVIVE,Stem Cells in Regenerative Biology and Medicine(2010), ANR-17-CE14-0038,MGonDev,Etude des mécanismes du développement des gonades chez l'homme(2017), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), ANR-10-LABX-0073/10-LABX-0073,REVIVE,Stem Cells in Regenerative Biology and Medicine(2010), ANR-17-CE14-0038,MGonDev,Etude des mécanismes du développement des gonades chez l’homme(2017), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Maladies génétiques d'expression pédiatrique (U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), National Research Center [Caire, Egypte], and Université de Genève = University of Geneva (UNIGE)
Subjects: Male, 0301 basic medicine, Somatic cell, Ribosomopathy, Gonadal dysgenesis, 030105 genetics & heredity, ribosomopathy, XY gonadal dysgenesis, Mice, Mutation Rate, Testis, Missense mutation, ddc:576.5, Testicular regression syndrome, Exome, testicular regression syndrome, Genetics (clinical), Gonadal Dysgenesis, 46,XY, Sanger sequencing, Genetics, disorders of sex development (DSD), RNA Helicase A, 3. Good health, Child, Preschool, symbols, Female, RNA Helicases, Heterozygote, endocrine system, DHX37, RNA helicase, Adolescent, Mutation, Missense, Biology, Article, Young Adult, 03 medical and health sciences, symbols.namesake, Protein Domains, medicine, Animals, Humans, Genetic Predisposition to Disease, urogenital system, Infant, Newborn, Sequence Analysis, DNA, medicine.disease, 030104 developmental biology, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, Mutagenesis, Site-Directed
Abstract: International audience; PURPOSE:XY individuals with disorders/differences of sex development (DSD) are characterized by reduced androgenization caused, in some children, by gonadal dysgenesis or testis regression during fetal development. The genetic etiology for most patients with 46,XY gonadal dysgenesis and for all patients with testicular regression syndrome (TRS) is unknown.METHODS:We performed exome and/or Sanger sequencing in 145 individuals with 46,XY DSD of unknown etiology including gonadal dysgenesis and TRS.RESULTS:Thirteen children carried heterozygous missense pathogenic variants involving the RNA helicase DHX37, which is essential for ribosome biogenesis. Enrichment of rare/novel DHX37 missense variants in 46,XY DSD is highly significant compared with controls (P value = 5.8 × 10-10). Five variants are de novo (P value = 1.5 × 10-5). Twelve variants are clustered in two highly conserved functional domains and were specifically associated with gonadal dysgenesis and TRS. Consistent with a role in early testis development, DHX37 is expressed specifically in somatic cells of the developing human and mouse testis.CONCLUSION:DHX37 pathogenic variants are a new cause of an autosomal dominant form of 46,XY DSD, including gonadal dysgenesis and TRS, showing that these conditions are part of a clinical spectrum. This raises the possibility that some forms of DSD may be a ribosomopathy.
Published: 2020
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43. Chikungunya resurgence in the Maldives and risk for importation via tourists to Europe in 2019-2020: A GeoSentinel case series

Author: Inés Oliveira Souto, Carsten Schade Larsen, Davidson H. Hamer, Martin P. Grobusch, Vanessa Field, Philippe Gautret, Marta Díaz-Menéndez, Frank von Sonnenburg, Philippe Parola, Pierre Dudouet, Federico Gobbi, Denis Malvy, Hilmir Asgeirsson, Emilie Javelle, Elena Trigo, Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Aarhus University Hospital, Instituto de Investigacion Hospital La Paz (IdiPAZ), Foundation for Biomedical Research, Hospital Universitario La Paz [Madrid, Spain]-Hospital Universitario La Paz [Madrid, Spain]-Hospital Universitario La Paz-School of Nursing Building, University of Munich Medical Center, Partenaires INRAE, IRCCS Sacro Cuore Don Calabria Hospital [Vérone, Italie], University of Amsterdam [Amsterdam] (UvA), CHU Bordeaux [Bordeaux], University College London Hospitals (UCLH), Karolinska Institutet [Stockholm], Universitat Autònoma de Barcelona (UAB), Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Hôpital d'Instruction des Armées Laveran, Service de Santé des Armées, Infectious diseases, AII - Infectious diseases, APH - Aging & Later Life, and APH - Global Health
Subjects: medicine.medical_specialty, 030231 tropical medicine, Mosquito Vectors, Health benefits, medicine.disease_cause, Arbovirus, Article, Disease Outbreaks, Tourism, IDLIC, 03 medical and health sciences, 0302 clinical medicine, Aedes, Indian Ocean Islands, Germany, Epidemiology, Vector-borne disease, medicine, Animals, Humans, 030212 general & internal medicine, Chikungunya, Socioeconomics, Travel, biology, Zika Virus Infection, GeoSentinel, Public Health, Environmental and Occupational Health, Outbreak, virus diseases, Zika Virus, biology.organism_classification, medicine.disease, 3. Good health, Europe, Infectious Diseases, Geography, Italy, Spain, Chikungunya Fever, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Health information, France
Abstract: Background Chikungunya virus (CHIKV) is an arthropod-borne virus mainly transmitted in tropical areas by Aedes spp. mosquitoes. It has been responsible for small-to-large outbreaks in temperate areas including southern Europe and North America. Past outbreaks in 2006 on the islands of Maldives, as well as on other islands in the Indian Ocean and in Southeast Asia, demonstrated for the first time the capacity of CHIKV to disseminate through travel and transcontinental commerce, and revealed the major socio-economic impact of CHIKV epidemics. Recently, CHIKV has been circulating in highly touristic areas including the Maldives, where 1736 cases were notified by the Health Protection Agency during 2019. Case series Among EuroTravNet/GeoSentinel patient records, eight CHIKV-confirmed cases imported the Maldives to France, Germany, Denmark, Italy and Spain were identified between February 2019 and February 2020; exceeding the total number of CHIKV infections travel-acquired in Maldives reported to this surveillance network during the previous 10 years. Conclusions The prevention and control of CHIKV introduction into naive areas colonised by competent vectors is crucial. CHIKV outbreaks must be detected and reported in a timely manner. This must lead to adapted health information for international travellers and to prompt management of suspected imported cases. Conversely, travellers make for excellent sentinels and increased reports of imported cases might reflect a change in the level of endemicity or even herald an outbreak. Feedback to the local health authorities and matching this with local epidemiological surveillance data may lead to health benefits for the local population.
Published: 2020
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44. Mapping the caribbean scientific collaboration.: Can mobility of researchers help?

Author: Palacios-Callender, M., Jáuregui-Haza, Ulises, Almira-Suarez, E.L., Mitchison, M., Cristobal Liz, R., Marcet-Garcia, E., Roberts, S.A., King‘s College London, Academic Studies. Caribbean Applied Science and Technology (ASCAST), Instituto Tecnológico de Santo Domingo (INTEC [República Dominicana]), University College London Hospitals (UCLH), and University of West London
Subjects: [SHS.HISPHILSO]Humanities and Social Sciences/History, Philosophy and Sociology of Sciences
Abstract: International audience; Caribbean communities were mobile long before European colonization and their modes of production and culture were evolving by frequent exchanges among the Caribbean islanders and the Northern coast of South America. However, the region has not fully benefited by the advent of the five Technological Revolutions since 1771. Moreover, in the last two decades of the XX century, the Caribbean Small Islands Developing States (SIDS) were severely affected by the migration of their tertiary educated population towards the developed world, a trend that continues today.Bibliometric approaches have been used to identify not only the brain drain, but also how the contemporary knowledge is created through the international network of scientific collaboration. In this study we use the Scopus bibliographic database to analyse the scientific output and international collaboration of the 13 Caribbean SIDS in the period between 2000 and 2018. The main scientific collaborator of the region as a country is United States, except for Cuba, which is Spain. Consequently, North America, Europe and the Caribbean islands share the higher proportion of co-authoring articles. In terms of institutional representation, the University of West Indies has, in aggregate, the highest output with 11,497 documents from 11 out of 13 SIDS. The main contributor as a country is Jamaica (5018), followed by Trinidad and Tobago. A group of high output academic institutions are University of Havana (4979), followed by Universidad Central de Las Villas, Institute of Tropical Medicine Pedro Kouri and the Centre of Genetic Engineering and Biotechnology, all of them in Cuba and with no significant collaboration with the rest of the region.In previous bibliometric studies we found that the scientists working abroad has the potential to become agents for development of the home country and region, diversifying the scientific collaboration.
Published: 2019

45. A Novel Intelligent Scan Assistant System for Early Pregnancy Diagnosis by Ultrasound: Clinical Decision Support System Evaluation Study

Author: Dhombres, Ferdinand, Maurice, Paul, Guilbaud, Lucie, Franchinard, Loriane, Dias, Barbara, Charlet, Jean, Blondiaux, Eléonore, Khoshnood, Babak, Jurkovic, Davor, Jauniaux, Eric, Jouannic, Jean-Marie, Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé (LIMICS), Université Paris 13 (UP13)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris 13 (UP13)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Radiologie [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Université Paris Descartes - Paris 5 (UPD5)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Women's Health [London], University College London Hospitals (UCLH), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), and Gestionnaire, Hal Sorbonne Université
Subjects: medicine.medical_specialty, 020205 medical informatics, decision support system, Image quality, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Health Informatics, Early pregnancy factor, 02 engineering and technology, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Clinical decision support system, medical ultrasound, Pregnancy, 0202 electrical engineering, electronic engineering, information engineering, medicine, Humans, ontology, Ultrasonography, Original Paper, biology, Ectopic pregnancy, business.industry, Ultrasound, Decision Support Systems, Clinical, medicine.disease, [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Early Diagnosis, Transvaginal ultrasound, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Quality Score, biology.protein, ectopic pregnancy, Female, knowledge base, Radiology, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], business
Abstract: International audience; BACKGROUND: Early pregnancy ultrasound scans are usually performed by nonexpert examiners in obstetrics/gynecology (OB/GYN) emergency departments. Establishing the precise diagnosis of pregnancy location is key for appropriate management of early pregnancies, and experts are usually able to locate a pregnancy in the first scan. A decision-support system based on a semantic, expert-validated knowledge base may improve the diagnostic performance of nonexpert examiners for early pregnancy transvaginal ultrasound.OBJECTIVE: This study aims to evaluate a novel Intelligent Scan Assistant System for early pregnancy ultrasound to diagnose the pregnancy location and determine the image quality.METHODS: Two trainees performed virtual transvaginal ultrasound examinations of early pregnancy cases with and without the system. The ultrasound images and reports were blindly reviewed by two experts using scoring methods. A diagnosis of pregnancy location and ultrasound image quality were compared between scans performed with and without the system.RESULTS: Each trainee performed a virtual vaginal examination for all 32 cases with and without use of the system. The analysis of the 128 resulting scans showed higher quality of the images (quality score: +23%; P
Published: 2019
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46. Recommendations for the design of therapeutic trials for neonatal seizures

Author: Soul, Janet S, Pressler, Ronit, Allen, Marilee, Boylan, Geraldine, Rabe, Heike, Portman, Ron, Hardy, Pollyanna, Zohar, Sarah, Romero, Klaus, Tseng, Brian, Bhatt-Mehta, Varsha, Hahn, Cecil, Denne, Scott, Auvin, Stephane, Vinks, Alexander, Lantos, John, Marlow, Neil, Davies, Jonathan M, for the International Neonatal Consortium, Boston Children's Hospital, Harvard Medical School [Boston] (HMS), University College of London [London] (UCL), Johns Hopkins University (JHU), University College Cork (UCC), Brighton and Sussex Medical School (BSMS), University of Birmingham [Birmingham], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Sorbonne Université (SU), University of Michigan [Ann Arbor], University of Michigan System, The Hospital for sick children [Toronto] (SickKids), University of Toronto, Neuroprotection du Cerveau en Développement / Promoting Research Oriented Towards Early Cns Therapies (PROTECT), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP Hôpital universitaire Robert-Debré [Paris], Cincinnati Children's Hospital Medical Center, University of Cincinnati (UC), Institute for Women's Health [London], University College London Hospitals (UCLH), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Research design, Protocol (science), medicine.medical_specialty, Randomization, Inclusion (disability rights), business.industry, [SDV]Life Sciences [q-bio], MEDLINE, Therapeutic trials, Neonatal seizures, Patient advocacy, 3. Good health, Clinical trial, 03 medical and health sciences, RJ0251, 0302 clinical medicine, 030225 pediatrics, Pediatrics, Perinatology and Child Health, medicine, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Well-designed clinical trials, Intensive care medicine, business, 030217 neurology & neurosurgery, Pharmaceutical industry
Abstract: International audience; Although seizures have a higher incidence in neonates than any other age group and are associated with significant mortality and neurodevelopmental disability, treatment is largely guided by physician preference and tradition, due to a lack of data from well-designed clinical trials. There is increasing interest in conducting trials of novel drugs to treat neonatal seizures, but the unique characteristics of this disorder and patient population require special consideration with regard to trial design. The Critical Path Institute formed a global working group of experts and key stakeholders from academia, the pharmaceutical industry, regulatory agencies, neonatal nurse associations, and patient advocacy groups to develop consensus recommendations for design of clinical trials to treat neonatal seizures. The broad expertise and perspectives of this group were invaluable in developing recommendations addressing: (1) use of neonate-specific adaptive trial designs, (2) inclusion/exclusion criteria, (3) stratification and randomization, (4) statistical analysis, (5) safety monitoring, and (6) definitions of important outcomes. The guidelines are based on available literature and expert consensus, pharmacokinetic analyses, ethical considerations, and parental concerns. These recommendations will ultimately facilitate development of a Master Protocol and design of efficient and successful drug trials to improve the treatment and outcome for this highly vulnerable population.
Published: 2019
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47. Hearing Protection, Restoration, and Regeneration

Author: Lawrence R. Lustig, Hinrich Staecker, Carina S Gomes-Santos, Ralph Holme, Matthew P Su, Thomas Lenarz, Athanasia Warnecke, Anne G M Schilder, Helen Blackshaw, Saaid Safieddine, University College of London [London] (UCL), University College London Hospitals (UCLH), Columbia University [New York], University of Kansas Medical Center [Lawrence], Hannover Medical School [Hannover] (MHH), Deutsche Forschungsgemeinschaft - German Research Foundation (DFG), Génétique et Physiologie de l'Audition, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Action on Hearing Loss [London], University of Kansas Medical Center [Kansas City, KS, USA], Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Sorbonne University, Pierre and Marie Curie University Paris, Paris, France
Subjects: medicine.medical_specialty, Drug Industry, MEDLINE, Audiology, Regenerative Medicine, Cell therapy, Hearing protection, 03 medical and health sciences, Otolaryngology, 0302 clinical medicine, Gene therapy, Clinical trials, Hearing Aids, Otoprotection, Inner ear, medicine, otorhinolaryngologic diseases, Regeneration, Humans, 030223 otorhinolaryngology, Hearing Loss, business.industry, Regeneration (biology), Grey literature, Sensory Systems, 3. Good health, Search terms, medicine.anatomical_structure, Otorhinolaryngology, Ear, Inner, Small molecules OR Drug Therapy OR Pharmacological Therapy, Neurology (clinical), business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Biotechnology
Abstract: International audience; OBJECTIVE: To provide an overview of biotechnology and pharmaceutical companies active in the field of inner ear and central hearing disorders and their therapeutic approaches.METHODS: Scientific and grey literature was searched using broad search terms to identify companies and their hearing-related therapeutic approaches. For each approach its lead indication, product, therapeutic modality, target, mechanism of action and current phase of clinical development was collated.RESULTS: A total of 43 biotechnology and pharmaceutical companies have been identified that are developing therapeutics for inner ear and central hearing disorders. Their therapeutics include drug-, cell- and gene-based approaches to prevent hearing loss or its progression, restore hearing, and regenerate the inner ear. Their therapeutic targets and specific mechanisms of action are wide-ranging, reflecting the complexity of the hearing pathways and the diversity of mechanisms underlying inner ear disorders. While none of the novel products under investigation have yet made it to the clinical market, and a large proportion are still at preclinical phase, many therapeutics have already entered clinical testing with more expected to do so in the next few years.CONCLUSION: A wide range of novel therapeutics targeting different hearing, balance and tinnitus pathways, and patient populations are approaching the clinical domain. It is important that clinicians involved in the care of patients with hearing loss prepare for what may become a radically different approach to the management of hearing disorders, and develop a true understanding of the new therapies' mechanisms of action, applications, and indications.
Published: 2019
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48. Multi-Ancestry Genome-Wide Association Study of Spontaneous Clearance of Hepatitis C Virus

Author: Gregory D. Kirk, Raymond T. Chung, Priya Duggal, Alessandra Mangia, David L. Thomas, Margaret A. Taub, Brian R. Edlin, Rachel Latanich, Chloe L. Thio, Edward L. Murphy, Salim I. Khakoo, Alex H. Kral, Graeme J.M. Alexander, Thomas R. O'Brien, Hugo R. Rosen, Valeria Piazzolla, Sharyne M. Donfield, Shruti H. Mehta, James J. Goedert, Georg M. Lauer, Marion G. Peters, Arthur Y. Kim, Eric O. Johnson, Michael P. Busch, Andrea L. Cox, Matthew E. Cramp, Ana Valencia, Candelaria Vergara, Genevieve L. Wojcik, Laurent Alric, Johns Hopkins University (JHU), Research Triangle Institute International (RTI International), National Institutes of Health [Bethesda] (NIH), Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Casa Sollievo della Sofferenza [San Giovanni Rotondo] (IRCCS), Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University School of Medicine [Baltimore], Massachusetts General Hospital [Boston], Harvard Medical School [Boston] (HMS), University of California (UC), University of Southampton, Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), SUNY Downstate Medical Center, State University of New York (SUNY), University College London Hospitals (UCLH), University of Colorado [Colorado Springs] (UCCS), Stanford University, University of California, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Hôpital Purpan [Toulouse], and CHU Toulouse [Toulouse]
Subjects: 0301 basic medicine, Male, Linkage disequilibrium, [SDV]Life Sciences [q-bio], Remission, Spontaneous, Genome-wide association study, Hepacivirus, medicine.disease_cause, Hepatitis, Receptors, G-Protein-Coupled, Major Histocompatibility Complex, 0302 clinical medicine, Genotype, Receptors, MESH: Interleukins / genetics, Medicine, GWAS, MESH: Interferons, Liver Disease, Gastroenterology, virus diseases, Hispanic or Latino, Blacks, Viral Load, Hepatitis C, 3. Good health, Infectious Diseases, Host-Pathogen Interactions, MESH: Major Histocompatibility Complex / genetics, MESH: African Continental Ancestry Group / genetics, 030211 gastroenterology & hepatology, Female, Infection, MESH: Viral Load, Risk, MESH: European Continental Ancestry Group / genetics, Remission, Hepatitis C virus, Chronic Liver Disease and Cirrhosis, Clinical Sciences, MESH: Hepatitis C / diagnosis, Black People, SNP, Single-nucleotide polymorphism, White People, Article, Paediatrics and Reproductive Medicine, 03 medical and health sciences, G-Protein-Coupled, Hepatitis - C, MESH: Hepacivirus / physiology, Genetics, Humans, 1000 Genomes Project, Cytokine, MESH: Hepatitis C / ethnology, MESH: Humans, Hepatology, Gastroenterology & Hepatology, business.industry, Whites, Spontaneous, Interleukins, MESH: Remission, Spontaneous, Human Genome, MESH: Host-Pathogen Interactions, MESH: Receptors, G-Protein-Coupled / genetics, Neurosciences, MESH: Hepatitis C / genetics, Odds ratio, MESH: Hispanic Americans / genetics, United States, digestive system diseases, MESH: Male, MESH: United States / epidemiology, 030104 developmental biology, Emerging Infectious Diseases, Good Health and Well Being, MESH: Hepatitis C / virology, Immunology, MESH: Genome-Wide Association Study, Interferons, business, Digestive Diseases, MESH: Female, Genome-Wide Association Study
Abstract: Background & aimsSpontaneous clearance of hepatitis C virus (HCV) occurs in approximately 30% of infected persons and less often in populations of African ancestry. Variants in major histocompatibility complex (MHC) and in interferon lambda genes are associated with spontaneous HCV clearance, but there have been few studies of these variants in persons of African ancestry. We performed a dense multi-ancestry genome-wide association study of spontaneous clearance of HCV, focusing on individuals of African ancestry.MethodsWe performed genotype analyses of 4423 people from 3 ancestry groups: 2201 persons of African ancestry (445 with HCV clearance and 1756 with HCV persistence), 1739 persons of European ancestry (701 with HCV clearance and 1036 with HCV persistence), and 486 multi-ancestry Hispanic persons (173 with HCV clearance and 313 with HCV persistence). Samples were genotyped using Illumina (San Diego, CA) arrays and statistically imputed to the 1000 Genomes Project. For each ancestry group, the association of single-nucleotide polymorphisms with HCV clearance was tested by log-additive analysis, and then a meta-analysis was performed.ResultsIn the meta-analysis, significant associations with HCV clearance were confirmed at the interferon lambda gene locus IFNL4-IFNL3 (19q13.2) (P= 5.99× 10-50) and the MHC locus 6p21.32 (P= 1.15× 10-21). We also associated HCV clearance with polymorphisms in the G-protein-coupled receptor 158 gene (GPR158) at 10p12.1 (P= 1.80× 10-07). These 3 loci had independent, additive effects of HCV clearance, and account for 6.8% and 5.9% of the variance of HCV clearance in persons of European and African ancestry, respectively. Persons of African or European ancestry carrying all 6 variants were 24-fold and 11-fold, respectively, more likely to clear HCV infection compared with individuals carrying none or 1 of the clearance-associated variants.ConclusionsIn a meta-analysis of data from 3 studies, we found variants in MHC genes, IFNL4-IFNL3, and GPR158 to increase odds of HCV clearance in patients of European and African ancestry. These findings could increase our understanding of immune response to and clearance of HCV infection.
Published: 2019
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49. Spatial descriptions of radiotherapy dose: normal tissue complication models and statistical associations

Author: Martin A. Ebert, Tiziana Rancati, Todd McNutt, Claudio Fiorino, Marnix G. Witte, Oscar Acosta, Sarah L. Gulliford, W. Heemsbergen, Giuseppe Palma, Renaud de Crevoisier, Sir Charles Gairdner Hospital, University College London Hospitals (UCLH), Laboratoire Traitement du Signal et de l'Image (LTSI), 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), CRLCC Eugène Marquis (CRLCC), Johns Hopkins University (JHU), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Netherlands Cancer Institute (NKI), Antoni van Leeuwenhoek Hospital, Consiglio Nazionale delle Ricerche (CNR), Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Ospedale San Raffaele, ME acknowledges funding support from the National Health and Medical Research Council (NHMRC grant 1077788). TR was partially supported by the Fondazione Italo Monzino. OA and RD acknowledge partial funding from a French government grant (through the CominLabs excellencelaboratory and managed by the National Research Agency in the ‘‘Investing for the Future' program, under reference ANR-10-LABX-07-01). SG is supported by a Cancer Research UK Centres Network Accelerator Award Grant (A21993) to the ART-NET Consortium., ANR-10-LABX-0007,COMIN Labs,Digital Communication and Information Sciences for the Future Internet(2010), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), Radiotherapy, Jonchère, Laurent, and Digital Communication and Information Sciences for the Future Internet - - COMIN Labs2010 - ANR-10-LABX-0007 - LABX - VALID
Subjects: complications, Computer science, Normal tissue, [SDV.CAN]Life Sciences [q-bio]/Cancer, Dose distribution, Machine learning, computer.software_genre, Radiotherapy dosimetry, 030218 nuclear medicine & medical imaging, modelling, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Dosimetry, Radiotherapy dose, Radiology, Nuclear Medicine and imaging, Radiometry, Radiation treatment planning, radiotherapy, Probability, [SDV.IB] Life Sciences [q-bio]/Bioengineering, Models, Statistical, Data collection, dosimetry, Radiological and Ultrasound Technology, Artificial neural network, business.industry, Radiotherapy Planning, Computer-Assisted, Radiotherapy Dosage, 3. Good health, 030220 oncology & carcinogenesis, Radiation Oncology, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Artificial intelligence, business, computer
Abstract: International audience; For decades, dose-volume information for segmented anatomy has provided the essential data for correlating radiotherapy dosimetry with treatment-induced complications. Dose-volume information has formed the basis for modelling those associations via normal tissue complication (NTCP) models and for driving treatment planning. Limitations to this approach have been identified. Many studies have emerged demonstrating that the incorporation of information describing the spatial nature of the dose distribution, and potentially its correlation with anatomy, can provide more robust associations with toxicity and seed more general NTCP models. Such approaches are culminating in the application of computationally intensive processes such as machine learning and the application of neural networks. The opportunities these approaches have for individualising treatment, predicting toxicity and expanding the solution space for radiation therapy are substantial and have clearly widespread and disruptive potential. Impediments to reaching that potential include issues associated with data collection, model generalisation and validation. This review examines the role of spatial models of complication and summarises relevant published studies. Sources of data for these studies, appropriate statistical methodology, frameworks for processing spatial dose information and extracting relevant features are described. Spatial complication modelling is consolidated as a pathway to guiding future developments towards effective, complication-free radiotherapy treatment.
Published: 2021
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50. Mapping the caribbean scientific collaboration

Author: Palacios-Callender, M., Jáuregui-Haza, Ulises, Almira-Suarez, E.L., Mitchison, M., Cristobal Liz, R., Marcet-Garcia, E., Roberts, S.A., FALCO, Eliane, King‘s College London, Academic Studies. Caribbean Applied Science and Technology (ASCAST), Instituto Tecnológico de Santo Domingo (INTEC [República Dominicana]), University College London Hospitals (UCLH), and University of West London
Subjects: [SHS.HISPHILSO]Humanities and Social Sciences/History, Philosophy and Sociology of Sciences, [SHS.HISPHILSO] Humanities and Social Sciences/History, Philosophy and Sociology of Sciences
Abstract: International audience; Caribbean communities were mobile long before European colonization and their modes of production and culture were evolving by frequent exchanges among the Caribbean islanders and the Northern coast of South America. However, the region has not fully benefited by the advent of the five Technological Revolutions since 1771. Moreover, in the last two decades of the XX century, the Caribbean Small Islands Developing States (SIDS) were severely affected by the migration of their tertiary educated population towards the developed world, a trend that continues today.Bibliometric approaches have been used to identify not only the brain drain, but also how the contemporary knowledge is created through the international network of scientific collaboration. In this study we use the Scopus bibliographic database to analyse the scientific output and international collaboration of the 13 Caribbean SIDS in the period between 2000 and 2018. The main scientific collaborator of the region as a country is United States, except for Cuba, which is Spain. Consequently, North America, Europe and the Caribbean islands share the higher proportion of co-authoring articles. In terms of institutional representation, the University of West Indies has, in aggregate, the highest output with 11,497 documents from 11 out of 13 SIDS. The main contributor as a country is Jamaica (5018), followed by Trinidad and Tobago. A group of high output academic institutions are University of Havana (4979), followed by Universidad Central de Las Villas, Institute of Tropical Medicine Pedro Kouri and the Centre of Genetic Engineering and Biotechnology, all of them in Cuba and with no significant collaboration with the rest of the region.In previous bibliometric studies we found that the scientists working abroad has the potential to become agents for development of the home country and region, diversifying the scientific collaboration.
Published: 2019

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