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1. Midbrain and pons MRI shape analysis and its clinical and CSF correlates in degenerative parkinsonisms: a pilot study

Author: C. Painous, S. Pascual-Diaz, E. Muñoz-Moreno, V. Sánchez, JC. Pariente, A. Prats-Galino, M. Soto, M. Fernández, A. Pérez-Soriano, A. Camara, E. Muñoz, F. Valldeoriola, N. Caballol, C. Pont-Sunyer, N. Martin, M. Basora, M. Tio, J. Rios, MJ. Martí, N. Bargalló, Y. Compta, [Painous C] Parkinson’s Disease & Movement Disorders Unit, Parkinson’s Disease and Other Degenerative Movement Disorders Team, Neurology Service, Hospital Clínic de Barcelona, IDIBAPS, CIBERNED (CB06/05/0018-ISCIII), ERN-RND, Institut Clínic de Neurociències (UBNeuro), Department of Medicine, School of Medicine, Universitat de Barcelona, Catalonia, Barcelona, Spain. Lab of Parkinson Disease and Other Neurodegenerative Movement Disorders, Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Institut de Neurociències, Hospital Clínic de Barcelona, Institut de Neurociències (UBNeuro), Universitat de Barcelona, Catalonia, Barcelona, Spain. [Pascual-Diaz S] Magnetic Resonance Imaging Core Facility, Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain. Laboratory of Surgical Neuroanatomy (LSNA), Universitat de Barcelona, Barcelona, Spain. [Muñoz-Moreno E, Pariente JC] Magnetic Resonance Imaging Core Facility, Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain. [Sánchez V] Centre de Diagnostic Per La Imatge (CDIC), Hospital Clinic, Barcelona, Spain. [Prats-Galino A] Centre de Diagnostic Per La Imatge (CDIC), Hospital Clinic, Barcelona, Spain. Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain. [Pont-Sunyer C] Neurology Unit, Hospital General de Granollers, Universitat Internacional de Catalunya, Granollers, Spain, and Hospital General de Granollers
Subjects: Investigative Techniques::Chemistry Techniques, Analytical::Spectrum Analysis::Magnetic Resonance Spectroscopy [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Nervous System Diseases::Autonomic Nervous System Diseases::Primary Dysautonomias::Multiple System Atrophy [DISEASES], Steele-Richardson-Olszewski, Síndrome de, Ressonància magnètica, técnicas de investigación::técnicas de química analítica::análisis espectral::espectroscopia de resonancia magnética [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::enfermedades de los ganglios basales::trastornos parkinsonianos [ENFERMEDADES], Radiology, Nuclear Medicine and imaging, General Medicine, Parkinson, Malaltia de, enfermedades del sistema nervioso::enfermedades del sistema nervioso autónomo::disautonomías primarias::atrofia de múltiples sistemas [ENFERMEDADES], Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Basal Ganglia Diseases::Parkinsonian Disorders [DISEASES]
Abstract: Objectives To conduct brainstem MRI shape analysis across neurodegenerative parkinsonisms and control subjects (CS), along with its association with clinical and cerebrospinal fluid (CSF) correlates. Methodology We collected demographic and clinical variables, performed planimetric and shape MRI analyses, and determined CSF neurofilament-light chain (NfL) levels in 84 participants: 11 CS, 12 with Parkinson’s disease (PD), 26 with multiple system atrophy (MSA), 21 with progressive supranuclear palsy (PSP), and 14 with corticobasal degeneration (CBD). Results MSA featured the most extensive and significant brainstem shape narrowing (that is, atrophy), mostly in the pons. CBD presented local atrophy in several small areas in the pons and midbrain compared to PD and CS. PSP presented local atrophy in small areas in the posterior and upper midbrain as well as the rostral pons compared to MSA. Our findings of planimetric MRI measurements and CSF NfL levels replicated those from previous literature. Brainstem shape atrophy correlated with worse motor state in all parkinsonisms and with higher NfL levels in MSA, PSP, and PD. Conclusion Atypical parkinsonisms present different brainstem shape patterns which correlate with clinical severity and neuronal degeneration. In MSA, shape analysis could be further explored as a potential diagnostic biomarker. By contrast, shape analysis appears to have a rather limited discriminant value in PSP. Key Points • Atypical parkinsonisms present different brainstem shape patterns. • Shape patterns correlate with clinical severity and neuronal degeneration. • In MSA, shape analysis could be further explored as a potential diagnostic biomarker.
Published: 2023

2. Mixed-method research protocol: Development and evaluation of a nursing intervention in patients discharged from the intensive care unit

Author: Ana Isabel Núñez Delgado, Cecilia Cuzco, Pilar Delgado-Hito, M. Antonia Martínez Momblan, Raquel Marín Pérez, Dolors Estrada Reventós, Gemma Martinez Estalella, Marta Romero García, Pedro Castro Rebollo, Institut Català de la Salut, [Cuzco C] Hospital Clinic, Barcelona, Spain. Faculty of Medicine and Health Sciences, School of Nursing, Department of Fundamental and Medical-Surgical Nursing, Universitat de Barcelona, Barcelona, Spain. Biomedical Research Institute August Pi Sunyer (IDIBAPS), Hospital Clinic Barcelona, Barcelona, Spain. [Castro Rebollo P] Hospital Clinic, Barcelona, Spain. Biomedical Research Institute August Pi Sunyer (IDIBAPS), Hospital Clinic Barcelona, Barcelona, Spain. School of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, Spain. [Marín Pérez R] Hospital Bellvitge, L'Hospitalet de Llobregat, Spain. [Núñez Delgado AI] Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Romero García M] Faculty of Medicine and Health Sciences, School of Nursing, Department of Fundamental and Medical-Surgical Nursing, Universitat de Barcelona, Barcelona, Spain. Nursing Research Group (GRIN), Bellvitge Biomedical Research Institute (IDIBELL), l’Hospitalet de Llobregat, Spain. [Martínez Momblan MA] Faculty of Medicine and Health Sciences, School of Nursing, Department of Fundamental and Medical-Surgical Nursing, Universitat de Barcelona, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: mixed‐method design, RT1-120, nursing intervention, Nursing, Anxiety, Hospital Anxiety and Depression Scale, law.invention, Nonprobability sampling, Hospitals, University, Study Protocol, post‐intensive care syndrome, law, Intervention (counseling), medicine, Humans, Multicenter Studies as Topic, Behavior and Behavior Mechanisms::Emotions::Anxiety [PSYCHIATRY AND PSYCHOLOGY], Unitats de cures intensives, General Nursing, business.industry, Multimethodology, ICU discharge, conducta y mecanismos de la conducta::emociones::ansiedad [PSIQUIATRÍA Y PSICOLOGÍA], diagnóstico::pronóstico::resultado del tratamiento [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Simple random sample, Diagnosis::Prognosis::Treatment Outcome [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Intensive care unit, Post-intensive care syndrome, Patient Discharge, Intensive Care Units, Ansietat, Health Care Facilities, Manpower, and Services::Health Facilities::Hospital Units::Intensive Care Units [HEALTH CARE], instalaciones, servicios y personal de asistencia sanitaria::centros sanitarios::unidades hospitalarias::unidades de cuidados intensivos [ATENCIÓN DE SALUD], Research Design, Avaluació de resultats (Assistència sanitària), medicine.symptom, business
Abstract: Alta de la UCI; Diseño de un método mixto; Intervención de enfermería Alta de la UCI; Disseny d'un mètode mixt; Intervenció d'infermeria ICU discharge; Mixed-method design; Nursing intervention Aim (a) To understand patients’ lived experience at intensive care unit (ICU) discharge and (b) to evaluate the impact of a nursing empowerment intervention (NEI) on patients’ anxiety and depression levels at ICU discharge. Design A mixed-methods approach will be applied. Methods In the qualitative phase, the hermeneutic phenomenological method will be used. Participants will be patients from three university hospitals who will be selected by purposive sampling. Data will be gathered through in-depth interviews and analysed using content analysis. The qualitative data obtained will be employed to develop the nursing intervention. Subsequently, a multicenter, parallel-group, experimental pre-test/post-test design with a control group will be used to measure the effectiveness of the nursing empowerment intervention in the quantitative phase by means of the Hospital Anxiety and Depression Scale (HADS). Simple random probabilistic sampling will include 172 patients in this phase.
Published: 2021

3. Integration of the ICD-11 and DSM-5 Dimensional Systems for Personality Disorders Into a Unified Taxonomy With Non-overlapping Traits

Author: Fernando Gutiérrez, Josep M. Peri, Miguel Gárriz, Gemma Vall, Estela Arqué, Laura Ruiz, Jaume Condomines, Natalia Calvo, Marc Ferrer, Bárbara Sureda, [Gutiérrez F] Institute of Neuroscience, Hospital Clinic, Barcelona, Spain. Institut d’Investigacións Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain. [Peri JM] Institute of Neuroscience, Hospital Clinic, Barcelona, Spain. [Gárriz M] Neuropsychiatry and Drug Addiction Institute, Parc de Salut Mar, Barcelona, Spain. [Vall G] Department of Psychiatry, Mental Health, and Addiction, GSS-Hospital Santa Maria, Lleida, Spain. Biomedical Research Institute, Lleida, Spain. [Arqué E, Ruiz L] La Coma Therapeutic Community, ATRA Group, Barcelona, Spain. [Calvo N, Ferrer M] Servei de Psiquiatria, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain. Departament de Psiquiatria i Medicina Legal, Universitat Autònoma de Barcelona, Bellaterra, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: 050103 clinical psychology, Mental Disorders::Personality Disorders [PSYCHIATRY AND PSYCHOLOGY], lcsh:RC435-571, media_common.quotation_subject, Ciencias de la información::servicios de información::documentación::Vocabulario controlado::Manual Diagnóstico y Estadístico de los Trastornos Mentales [CIENCIA DE LA INFORMACIÓN], Negative affectivity, DSM-5, 03 medical and health sciences, 0302 clinical medicine, ICD-11, Taxonomy (general), Psychoticism, lcsh:Psychiatry, medicine, Personality, 0501 psychology and cognitive sciences, personality disorders, Trastorns de la personalitat, general factor, Information Science::Information Services::Documentation::Vocabulary, Controlled::Diagnostic and Statistical Manual of Mental Disorders [INFORMATION SCIENCE], media_common, Malalties mentals - Classificació, 05 social sciences, Discriminant validity, medicine.disease, Personality disorders, 030227 psychiatry, Psychiatry and Mental health, Information Science::Information Services::Documentation::Vocabulary, Controlled::International Classification of Diseases [INFORMATION SCIENCE], trastornos mentales::trastornos de la personalidad [PSIQUIATRÍA Y PSICOLOGÍA], Ciencias de la información::servicios de información::documentación::Vocabulario controlado::Clasificación Internacional de Enfermedades [CIENCIA DE LA INFORMACIÓN], Personality Assessment Inventory, Psychology, Estadística mèdica, Cognitive psychology, discriminant validity
Abstract: DSM-5; CIE-11; Trastornos de la personalidad DSM-5; CIM-11; Trastorns de la personalitat DSM-5; ICD-11; Personality disorders The promise of replacing the diagnostic categories of personality disorder with a better-grounded system has been only partially met. We still need to understand whether our main dimensional taxonomies, those of the International Classification of Diseases, 11th Revision (ICD-11) and the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), are the same or different, and elucidate whether a unified structure is possible. We also need truly independent pathological domains, as they have shown unacceptable overlap so far. To inquire into these points, the Personality Inventory for DSM-5 (PID-5) and the Personality Inventory for ICD-11 (PiCD) were administered to 677 outpatients. Disattenuated correlation coefficients between 0.84 and 0.93 revealed that both systems share four analogous traits: negative affectivity, detachment, dissociality/antagonism, and disinhibition. These traits proved scalar equivalence too, such that scores in the two questionnaires are roughly interchangeable. These four domains plus psychoticism formed a theoretically consistent and well-fitted five-factor structure, but they overlapped considerably, thereby reducing discriminant validity. Only after the extraction of a general personality disorder factor (g-PD) through bifactor analysis, we could attain a comprehensive model bearing mutually independent traits. This work was supported by project PI15/00536, part of the Plan Estatal de Investigación Científica y Técnica y de Innovación 2013–2016, financed by the ISCIII Subdirección General de Evaluación, and cofinanced by the European Regional Development Fund (ERDF, A way to build Europe; PI: FG).
Published: 2021

4. The HIV-1 integrase-LEDGF allosteric inhibitor MUT-A: resistance profile, impairment of virus maturation and infectivity but without influence on RNA packaging or virus immunoreactivity

Author: François Moreau, Sophie Chasset, Felipe García, Marc Ruff, Ben Berkhout, Erwann Le Rouzic, Danièle Spehner, Benoit Ledoussal, Laia Miralles, Stéphane Emiliani, Francis Chevreuil, Igor Orlov, Alessia Zamborlini, Christiane Moog, Julie Brias, Bruno P. Klaholz, Nikki van Bel, Céline Amadori, José M. Gatell, Damien Bonnard, Luzia Mayr, Yme U. van der Velden, Richard Benarous, Montserrat Plana, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Les Laboratoires Biodim-Mutabilis [Romainville], Biocitech, Université Sorbonne Paris Cité (USPC), Laboratory of Experimental Virology - Department of Medical Microbiology [Amsterdam, The Netherlands], Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA)-Center for Infection and Immunity Amsterdam - CINIMA [Amsterdam, The Netherlands], Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), AIDS Research Group [Barcelona, Spain], Hospital Clinic [Barcelona, Spain]-August Pi i Sunyer Biomedical Research Institute - IDIBAPS [Barcelona, Spain], Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathologie cellulaire : aspects moléculaires et viraux / Pathologie et Virologie Moléculaire, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), This work was supported by Biodim Mutabilis under the Authorization Number DUO 2145, assigned by the French Ministry of Research for work with genetically modified organisms, and by Grants from EU FP7 to Biodim, BB, SE and AZ under the HIVINNOV consortium, Grant Agreement No. 305137, from the Eurostar Grant ResistAids to Biodim and BB (Grant Agreement No. E!10239) and by the French Infrastructure for Integrated Structural Biology (FRISBI) ANR-10-INSB-05-01, and Instruct as part of the European Strategy Forum on Research Infrastructures (ESFRI). Felipe García team was supported by Grants SAF2015-66193-R, SAF2012-39075, Montserrat Plana by Grant FIS PI15/00480 and Nikki van Bel by NWO-CW (TOP Grant)., ANR-10-INBS-0005,FRISBI,Infrastructure Française pour la Biologie Structurale Intégrée(2010), European Project: 305137,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,HIVINNOV(2012), Les Laboratoires Biodim-Mutabilis, Centre d'Economie de l'Université Paris Nord (CEPN), Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Centre National de la Recherche Scientifique (CNRS), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (UMR_S_944)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Collège de France (CdF (institution))-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (UMR_S567 / UMR 8104), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Center for Infection and Immunity Amsterdam (CINIMA), August Pi i Sunyer Biomedical Research Institute - IDIBAPS [Barcelona, Spain]-Hospital Clinic [Barcelona, Spain], Collège de France (CdF (institution))-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Collège de France (CdF)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Immunorhumathologie moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM), ANR-10-INBS-05-01/10-INBS-0005,FRISBI,Infrastructure Française pour la Biologie Structurale Intégrée(2010), Klaholz, Bruno, Infrastructure Française pour la Biologie Structurale Intégrée - - FRISBI2010 - ANR-10-INBS-0005 - INBS - VALID, Generation of a new class of antiretrovirals targeting HIV-cellular cofactors interactions - HIVINNOV - - EC:FP7:HEALTH2012-10-01 - 2015-09-30 - 305137 - VALID, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Centre National de la Recherche Scientifique (CNRS), AII - Infectious diseases, Medical Microbiology and Infection Prevention, and Amsterdam institute for Infection and Immunity
Subjects: 0301 basic medicine, lcsh:Immunologic diseases. Allergy, Pyridines, Virus Integration, T cell, [SDV]Life Sciences [q-bio], Aucun, HIV Integrase, Thiophenes, Allosteric integrase inhibitor, HIV Antibodies, Virus Replication, Integrase, Virus, Cell Line, 03 medical and health sciences, INLAI, Immunoreactivity, Virology, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Virus maturation, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, LEDGIN, HIV Integrase Inhibitors, LEDGF, Infectivity, biology, Research, Virus Assembly, RNA, virus diseases, Group-specific antigen, Reverse transcriptase, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, Infectious Diseases, medicine.anatomical_structure, biology.protein, HIV-1, Intercellular Signaling Peptides and Proteins, lcsh:RC581-607
Abstract: Background HIV-1 Integrase (IN) interacts with the cellular co-factor LEDGF/p75 and tethers the HIV preintegration complex to the host genome enabling integration. Recently a new class of IN inhibitors was described, the IN-LEDGF allosteric inhibitors (INLAIs). Designed to interfere with the IN-LEDGF interaction during integration, the major impact of these inhibitors was surprisingly found on virus maturation, causing a reverse transcription defect in target cells. Results Here we describe the MUT-A compound as a genuine INLAI with an original chemical structure based on a new type of scaffold, a thiophene ring. MUT-A has all characteristics of INLAI compounds such as inhibition of IN-LEDGF/p75 interaction, IN multimerization, dual antiretroviral (ARV) activities, normal packaging of genomic viral RNA and complete Gag protein maturation. MUT-A has more potent ARV activity compared to other INLAIs previously reported, but similar profile of resistance mutations and absence of ARV activity on SIV. HIV-1 virions produced in the presence of MUT-A were non-infectious with the formation of eccentric condensates outside of the core. In studying the immunoreactivity of these non-infectious virions, we found that inactivated HIV-1 particles were captured by anti-HIV-specific neutralizing and non-neutralizing antibodies (b12, 2G12, PGT121, 4D4, 10-1074, 10E8, VRC01) with efficiencies comparable to non-treated virus. Autologous CD4+ T lymphocyte proliferation and cytokine induction by monocyte-derived dendritic cells (MDDC) pulsed either with MUT-A-inactivated HIV or non-treated HIV were also comparable. Conclusions Although strongly defective in infectivity, HIV-1 virions produced in the presence of the MUT-A INLAI have a normal protein and genomic RNA content as well as B and T cell immunoreactivities comparable to non-treated HIV-1. These inactivated viruses might form an attractive new approach in vaccine research in an attempt to study if this new type of immunogen could elicit an immune response against HIV-1 in animal models. Electronic supplementary material The online version of this article (10.1186/s12977-017-0373-2) contains supplementary material, which is available to authorized users.
Published: 2017

5. HIV therapeutic vaccine enhances non-exhausted CD4+ T cells in a randomised phase 2 trial

Author: Jacques Reynes, Alain Devidas, Béhazine Combadière, Yazdan Yazdanpanah, Patrice Debré, Laurence Weiss, Yasmine Dudoit, Laurent Cotte, Gilles Pialoux, Delphine Joyeux, Gerd Fätkenheuer, Roland Tubiana, Jürgen K. Rockstroh, Odile Launay, Shahin Gharakhanian, Christine Katlama, Vincent Vieillard, Pierre-Marie Girard, Felipe García, José M. Gatell, Brigitte Autran, Anne Simon, Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Tenon [AP-HP], Hospices Civils de Lyon (HCL), Hôpital de la Croix-Rousse [CHU - HCL], CHU Saint-Antoine [AP-HP], Université de Montpellier (UM), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Universitätsklinikum Bonn (UKB), Centre Hospitalier Sud Francilien, CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Université Sorbonne Paris Cité (USPC), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), University Hospital of Cologne [Cologne], German Centre for Infection Research (DZIF), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Pitié-Salpêtrière [APHP], CIC Cochin Pasteur (CIC 1417), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP]-Hôtel-Dieu-Université Paris Descartes - Paris 5 (UPD5)-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [APHP], Equipe 16, Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), AIDS Research Group [Barcelona, Spain], August Pi i Sunyer Biomedical Research Institute - IDIBAPS [Barcelona, Spain]-Hospital Clinic [Barcelona, Spain], CH Evry-Corbeil, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Immunité et Infection, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR113-Université Pierre et Marie Curie - Paris 6 (UPMC), Medicines Development Group (MDG), Vertex Pharmaceuticals, Gestionnaire, Hal Sorbonne Université, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Hôpital de la Croix-Rousse [CHU - HCL], Hospital Clinic [Barcelona, Spain]-August Pi i Sunyer Biomedical Research Institute - IDIBAPS [Barcelona, Spain], Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), and Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: lcsh:Immunologic diseases. Allergy, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Immunology, Placebo, lcsh:RC254-282, Gastroenterology, Peptide vaccines, 03 medical and health sciences, 0302 clinical medicine, Immune system, [SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology, Antigen, Internal medicine, Protocol, medicine, Pharmacology (medical), 030212 general & internal medicine, Adverse effect, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Pharmacology, 0303 health sciences, biology, business.industry, Immunogenicity, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Publisher Correction, 3. Good health, Vaccination, Infectious Diseases, Viral infection, biology.protein, Antibody, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, lcsh:RC581-607, business, CD8
Abstract: VAC-3S is a therapeutic vaccine comprising a highly conserved HIV-gp41 motif coupled with the CRM197 carrier protein. High levels of anti-3S antibodies (Abs) have been associated with improved protection of CD4+ T-cell survival. A previous phase 1 study demonstrated the safety of VAC-3S. This multicentre, randomised, double-blind, placebo-controlled phase 2 clinical trial enroled between January 2014 and March 2015 HIV-1-infected patients under ART with plasma HIV RNA levels below 50 copies/mL and CD4 counts between 200 and 500 cells/μL. Participants were immunised with 16, 32, or 64 μg of VAC-3S, and compared to placebo. The primary outcome was immunogenicity assessed by changes from baseline of anti-3S Abs levels at week 12. Secondary outcomes included adverse events and the course of plasma HIV RNA level, CD4 count, CD4/CD8 ratio, inflammation and immune checkpoints from week 0 to week 48. Vaccination was well tolerated with no serious adverse events and induced a significant increase in anti-3S Ab response in vaccinated patients (p + T cells through week 48 (variance p = 0.0017). PD-1 expression was correlated with level of anti-3S Abs (p = 0.0092, r = −0.68) and expression of NKp44L (p r = 0.54) in CD4+ T cells. Our findings regarding the increase of non-exhausted CD4+ T cells have potentially important application in personalised HIV vaccination for HIV-infected patients with high level of PD-1 to improve their T-cell immune function.
Published: 2019

6. Prosthetic Valve Candida spp. Endocarditis: New Insights Into Long-term Prognosis—The ESCAPE Study

Author: Rivoisy, Claire, Vena, Antonio, Schaeffer, Laura, Charlier, Caroline, Fontanet, Arnaud, Delahaye, François, Bouza, Emilio, Lortholary, Olivier, Lefort, Agnès, Yazdanpanah, Yazdan, Wolff, Michel, Houze, Sandrine, Ferry, Tristan, Wallon, Martine, Strady, Christophe, Toubas, Dominique, Bréchot, Nicolas, Henry, Benoit, Fekkar, Arnaud, Fourme, Thierry, Amouroux, Isabelle, Mainardi, Jean-Luc, Dannaoui, Eric, Rogeaux, Olivier, Levast, Marion, Chirouze, Catherine, Million, Laurence, Bastides, Frédéric, Chandenier, Jacques, Lançon, Jean-Pierre, Ovize, Anne, Abgueguen, Pierre, Bouchara, Jean-Philippe, Tric, Laurent, Habib, Gilbert, Gourriet, Frederic, Aaron, Laurent, Bougnoux, Marie Elisabeth, Camou, Fabrice, Accoceberry, Isabelle, Sánchez, Fernando Fernández, Noureddine, Mariam, Rosas, Gabriel, de la Torre Lima, Javier, Aramendi, José, Bereciartua, Elena, Victoria Boado, María, Campaña Lázaro, Marta, Goikoetxea, Josune, José Goiti, Juan, Hernández, José Luis, Iruretagoyena, José Ramón, Zuazabal, Josu Irurzun, López-Soria, Leire, Montejo, Miguel, Pérez, Pedro María, Rodríguez, Regino, Voces, Roberto, López, Mª Victoria García, Georgieva, Radka Ivanova, Solero, Manuel Márquez, Bailón, Isabel Rodríguez, Morales, Josefa Ruiz, Cuende, Ana María, Echeverría, Tomás, Fuerte, Ana, Gaminde, Eduardo, Goenaga, Miguel Ángel, Idígoras, Pedro, Iribarren, José Antonio, Yarza, Alberto Izaguirre, Urkola, Xabier Kortajarena, Reviejo, Carlos, Carrasco, Rafael, Climent, Vicente, Llamas, Patricio, Merino, Esperanza, Plazas, Joaquín, Reus, Sergio, Álvarez, Nemesio, Bravo-Ferrer, Jose María, Castelo, Laura, Cuenca, José, Llinares, Pedro, Rey, Enrique Miguez, Mayo, María Rodríguez, Sánchez, Efrén, Regueiro, Dolores Sousa, Martinez, Francisco Javier, del Mar Alonso, Mª, Castro, Beatriz, Marrero, Dácil García, Durán, Mª del Carmen, Gómez, Mª Antonia Miguel, Calzada, Juan La, Nassar, Ibrahim, Ciezar, Antonio Plata, Iglesias, José Mª Reguera, Asensio, Víctor, Costas, Carlos, de la Hera, Jesús, Suárez, Jonnathan Fernández, Fraile, Lisardo Iglesias, Arguero, Víctor León, Menéndez, José López, MenciaBajo, Pilar, Morales, Carlos, Torrico, Alfonso Moreno, Palomo, Carmen, Martínez, Begoña Paya, Esteban, Ángeles Rodríguez, García, Raquel Rodríguez, Asensio, Mauricio Telenti, Almela, Manuel, Armero, Yolanda, Azqueta, Manuel, Brunet, Merce, Cartañá, Ramón, Cervera, Carlos, Falces, Carlos, Fita, Guillermina, Fuster, David, de la Maria, Cristina García, Gatell, José, Pérez, Jaume Llopis, Marco, Francesc, Mestres, Carlos, Miró, José Mª, Moreno, Asunción, Ninot, Salvador, Quintana, Eduardo, Paré, Carlos, Pericás, Juan Manuel, Pomar, José, Ramírez, José, Rovira, Irene, Sitges, Marta, Soy, Dolors, Téllez, Adrián, Vila, Jordi, Bermejo, Javier, Cuerpo, Gregorio, de Egea, Viviana, Eworo, Alia, Cruz, Ana Fernández, Leoni, Mª Eugenia García, del Vecchio, Marcela González, Ramallo, Víctor González, Hernández, Martha Kestler, Marín, Mercedes, Martínez-Sellés, Manuel, Menárguez, Mª Cruz, Muñoz, Patricia, Rincón, Cristina, Rodríguez-Abella, Hugo, Rodríguez-Créixems, Marta, Pinilla, Blanca, Pinto, Ángel, Valerio, Maricela, Moreno, Eduardo Verde, Antorrena, Isabel, Loeches, Belén, Moreno, Mar, Ramírez, Ulises, Bastón, Verónica Rial, Romero, María, Saldaña, Araceli, Castillo, Carlos Armiñanzas, Arnaiz, Ana, Berrazueta, José, Bellisco, Sara, Belaustegui, Manuel Cobo, Durán, Raquel, Fariñas, MªCarmen, Fariñas-Álvarez, Concepción, Mazarrasa, Carlos Fernández, Izquierdo, Rubén Gómez, Rico, Claudia González, Díez, José Gutiérrez, Durán, Rafael Martín, Pajarón, Marcos, Parra, José Antonio, Teira, Ramón, Zarauza, Jesús, Pavía, Pablo García, González, Jesús, Orden, Beatriz, RAMOS, Antonio, González, Elena Rodríguez, Centella, Tomasa, Hermida, José Manuel, Luis Moya, José, Martín-Dávila, Pilar, Navas, Enrique, Oliva, Enrique, del Río, Alejandro, Ruiz, Soledad, Tenorio, Carmen Hidalgo, de Castro, Antonio, de Cueto, Marina, Gallego, Pastora, Acebal, Juan Gálvez, Baño, Jesús Rodríguez, de Alarcón, Arístides, García, Emilio, Haro, Juan Luis, Lepe, José Antonio, López, Francisco, Luque, Rafael, Alonso, Luis Javier, Gutiérrez, José Manuel Azcona, Blanco, José Ramón, García, Lara, Oteo, José Antonio, de Benito, Natividad, Gurguí, Mercé, Pacho, Cristina, Pericas, Roser, Pons, Guillem, Alvarez, M., Fernández, A, Prieto, A., Regueiro, Benito, Tijeira, E, Vega, Marino, Blasco, Andrés Canut, Mollar, José Cordo, Arana, Juan Carlos Gainzarain, Uriarte, Oscar García, López, Alejandro Martín, de Zárate, Zuriñe Ortiz, Matos, José Antonio Urturi, Nacle, Mª Belén, Sánchez-Porto, Antonio, Vallejo, Luis, ArribasLeal, José Mª, Vázquez, Elisa García, Torres, Alicia Hernández, Blázquez, Ana, de la Morena Valenzuela, Gonzalo, Alonso, Ángel, Aramburu, Javier, Calvo, Felicitas Elena, Rodríguez, Anai Moreno, Tarabini-Castellani, Paola, Gálvez, Eva Heredero, Bellido, Carolina Maicas, Pau, José Largo, Sepúlveda, Mª Antonia, Sierra, Pilar Toledano, Iqbal-Mirza, Sadaf Zafar, Alcolea, Eva Cascales, Serrano, Pilar Egea, Hernández Roca, José Joaquín, Service des Maladies infectieuses et tropicales [CHU Necker], Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP]-Institut des Maladies Génétiques Imagine [Paris], Hospital General Universitario 'Gregorio Marañón' [Madrid], Epidémiologie des Maladies Emergentes, Pasteur-Cnam risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre d'infectiologie Necker-Pasteur [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Mère et enfant face aux infections tropicales (MERIT - UMR_D 216), Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), Service de Parasitologie, Hospices Civils de Lyon (HCL)-Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP], Institut Élie Cartan de Lorraine (IECL), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [APHP], Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Mycologie moléculaire, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Service des Maladies Infectieuses, CHR Chambéry, Laboratoire de Bactériologie, Centre Hospitalier Régional de Chambéry, Laboratoire Chrono-environnement - UFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de Médecine Interne et Maladies Infectieuses [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), CHU Tours, Service de Parasitologie - Mycologie - Médecine Tropicale, Eurofins Biomnis [Lyon, France], Service des maladies infectieuses et tropicales [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Groupe d’Etude des Interactions Hôte-Pathogène, Université d'Angers (UA), Service de cardiologie, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Biologie et Pathogénicité fongiques, Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris], Hôpital St-André, Réanimation, CHU Bordeaux [Bordeaux], Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Universitad Politecnica de Alicante (UPA), Departamento de Lenguajes y Sistemas Informaticos, Instituto Tecnologico de Aragon (ITA), Instituto Tecnológico de Aragón, Department of Anatomy and Cell Biology [Montréal], McGill University, Universitat de Barcelona (UB), AIDS Research Group [Barcelona, Spain], August Pi i Sunyer Biomedical Research Institute - IDIBAPS [Barcelona, Spain]-Hospital Clinic [Barcelona, Spain], Instituto Tecnológico de Tláhuac, Cardiology Department, Thorax Clinic Institute, Hospital Cliınic, Institut d'Investigacions Biomèdiques [Barcelona], Clinical Microbiology and Infectious Diseases Department, Universidad Complutense de Madrid [Madrid] (UCM), Universidade de Aveiro, Departamento de Quimica Organica [Universidad de Cordoba], Universidad de Córdoba [Cordoba], Department of Microbiology, Hospital de la Santa Creu i Sant Pau, University Rovirai Virgili de Tarragona (URV), Chercheur indépendant, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-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)-Institut Pasteur [Paris] (IP)-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), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 216), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-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), 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)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Eurofins Biomnis, Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), Biologie et Pathogénicité fongiques (BPF), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP), Microbiologie Fondamentale et Pathogénicité (MFP), Instituto Tecnológico de Aragón (ITAINNOVA), McGill University = Université McGill [Montréal, Canada], Universidad de Córdoba = University of Córdoba [Córdoba], This work was supported by the Programa Multidisciplinar para la Gestión de Antifúngicos y la Reducción de Candidiasis Invasora (PROMULGA) II Project, Instituto de Salud Carlos III, partially financed by the European Regional Development Fund (grant PI13/01148). A. V. is supported by a Rio Hortega contract from the Instituto de Salud Carlos III, also partially financed by the European Regional Development Fund (grant CM15/00181)., Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Beaujon-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut Pasteur [Paris]-Institut National de la Recherche Agronomique (INRA), Hospital Clinic [Barcelona, Spain]-August Pi i Sunyer Biomedical Research Institute - IDIBAPS [Barcelona, Spain], and Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, 0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Antifungal Agents, Prosthesis-Related Infections, Echinocandin, 030106 microbiology, 03 medical and health sciences, Candida, endocarditis, prosthetic valve, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Amphotericin B, Internal medicine, Humans, Medicine, Endocarditis, Prospective Studies, Registries, Adverse effect, Prospective cohort study, Fluconazole, Survival rate, ComputingMilieux_MISCELLANEOUS, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Aged, Retrospective Studies, business.industry, Candidiasis, Disease Management, Retrospective cohort study, Odds ratio, Middle Aged, Prognosis, medicine.disease, 3. Good health, Infectious Diseases, Spain, Heart Valve Prosthesis, Female, France, business, medicine.drug
Abstract: International audience; Background: Prosthetic valve endocarditis caused by Candida spp. (PVE-C) is rare and devastating, with international guidelines based on expert recommendations supporting the combination of surgery and subsequent azole treatment.Methods: We retrospectively analyzed PVE-C cases collected in Spain and France between 2001 and 2015, with a focus on management and outcome.Results: Forty-six cases were followed up for a median of 9 months. Twenty-two patients (48%) had a history of endocarditis, 30 cases (65%) were nosocomial or healthcare related, and 9 (20%) patients were intravenous drug users. "Induction" therapy consisted mainly of liposomal amphotericin B (L-amB)-based (n = 21) or echinocandin-based therapy (n = 13). Overall, 19 patients (41%) were operated on. Patients
Published: 2018

7. Efficacy and Safety of Anakinra Plus Standard of Care for Patients With Severe COVID-19: A Randomized Phase 2/3 Clinical Trial

Author: Fanlo, Patricia, del Carmelo Gracia Tello, Borja, Fonseca Aizpuru, Eva, Álvarez-Troncoso, Jorge, Gonzalez, Andrés, Prieto-González, Sergio, Bujan Rivas, Segundo, Institut Català de la Salut, [Fanlo P] Unidad de Enfermedades Autoinmunes Sistémicas, Servicio de Medicina Interna, Hospital Universitario de Navarra, Pamplona, Spain. [Gracia-Tello BDC] Unidad de Enfermedades Autoinmunes Sistémicas, Servicio de Medicina Interna, Hospital Universitario Clínico Lozano Blesa, Zaragoza, Spain. [Fonseca Aizpuru E] Unidad de Enfermedades Autoinmunes Sistémicas, Servicio de Medicina Interna, Hospital de Cabueñes, Gijón, Spain. [Álvarez-Troncoso J] Unidad de Enfermedades Autoinmunes Sistémicas, Servicio de Medicina Interna, Hospital La Paz, Madrid, Spain. [Gonzalez A] Unidad de Enfermedades Autoinmunes Sistémicas, Servicio de Medicina Interna, Hospital Ramón y Cajal, Madrid, Spain. [Prieto-González S] Servicio de Enfermedades Autoinmunes Sistémicas, Hospital Clinic, Barcelona, Spain. [Buján-Rivas S] Unitat de Malalties Autoimmunes Sistèmiques, Servei de Medicina Interna, Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: COVID-19 (Malaltia) - Tractament, Avaluació de resultats (Assistència sanitària), virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES], Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], diagnóstico::pronóstico::resultado del tratamiento [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES], Other subheadings::Other subheadings::/drug therapy [Other subheadings], Diagnosis::Prognosis::Treatment Outcome [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT]
Abstract: Efficacy; Safety; COVID-19 Eficacia; Seguridad; COVID-19 Eficàcia; Seguretat; COVID-19 Importance COVID-19 pneumonia is often associated with hyperinflammation. The efficacy and safety of anakinra in treating patients with severe COVID-19 pneumonia and hyperinflammation are still unclear. Objective To assess the efficacy and safety of anakinra vs standard of care alone for patients with severe COVID-19 pneumonia and hyperinflammation. Design, Setting, and Participants The Clinical Trial of the Use of Anakinra in Cytokine Storm Syndrome Secondary to COVID-19 (ANA-COVID-GEAS) was a multicenter, randomized, open-label, 2-group, phase 2/3 clinical trial conducted at 12 hospitals in Spain between May 8, 2020, and March 1, 2021, with a follow-up of 1 month. Participants were adult patients with severe COVID-19 pneumonia and hyperinflammation. Hyperinflammation was defined as interleukin-6 greater than 40 pg/mL, ferritin greater than 500 ng/mL, C-reactive protein greater than 3 mg/dL (rationale, ≥5 upper normal limit), and/or lactate dehydrogenase greater than 300 U/L. Severe pneumonia was considered if at least 1 of the following conditions was met: ambient air oxygen saturation 94% or less measured with a pulse oximeter, ratio of partial pressure O2 to fraction of inspired O2 of 300 or less, and/or a ratio of O2 saturation measured with pulse oximeter to fraction of inspired O2 of 350 or less. Data analysis was performed from April to October 2021. Interventions Usual standard of care plus anakinra (anakinra group) or usual standard of care alone (SoC group). Anakinra was given at a dose of 100 mg 4 times a day intravenously. Main Outcomes and Measures The primary outcome was the proportion of patients not requiring mechanical ventilation up to 15 days after treatment initiation, assessed on an intention-to-treat basis. Results A total of 179 patients (123 men [69.9%]; mean [SD] age, 60.5 [11.5] years) were randomly assigned to the anakinra group (92 patients) or to the SoC group (87 patients). The proportion of patients not requiring mechanical ventilation up to day 15 was not significantly different between groups (64 of 83 patients [77.1%] in the anakinra group vs 67 of 78 patients [85.9%] in the SoC group; risk ratio [RR], 0.90; 95% CI, 0.77-1.04; P = .16). Anakinra did not result in any difference in time to mechanical ventilation (hazard ratio, 1.72; 95% CI, 0.82-3.62; P = .14). There was no significant difference between groups in the proportion of patients not requiring invasive mechanical ventilation up to day 15 (RR, 0.99; 95% CI, 0.88-1.11; P > .99). Conclusions and Relevance In this randomized clinical trial, anakinra did not prevent the need for mechanical ventilation or reduce mortality risk compared with standard of care alone among hospitalized patients with severe COVID-19 pneumonia. Funding for this study was received from the Regional Government of Navarra, Spain (project 0011-3597-2020-000028 to Dr Fanlo), and drugs were provided by the company Swedish Orphan Biovitrum (Sobi).
Published: 2023

8. Predictors of right atrial dilatation and long-term function after right ventricular outflow tract surgical repair: Quantification of restrictive physiology matters

Author: Maria Antonia Pijuan-Domènech, Silvia Montserrat, Victor Pineda, Filipa Valente, Ignacio Ferreira-Gonzalez, Josep-Ramon Marsal, Miguel Angel Castro-Alba, Carlos Sureda-Barbosa, Berta Miranda-Barrio, Maria Teresa Subirana-Domènech, Laura Dos-Subirà, Jaume Casaldàliga-Ferrer, Institut Català de la Salut, [Pijuan-Domènech MA, Miranda-Barrio B, Dos-Subirà L] Unitat Integrada de Cardiopaties Congènites de l’Adolescent i l’Adult, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Hospital Sant Pau, Barcelona, Spain. Servei de Cardiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Centro de Investigación en Red de Enfermedades Cardiovasculares (CIBERCV), Spain. [Montserrat S] Department of Cardiology, Cardiovascular Institute, Hospital Clinic Barcelona, Spain. [Pineda V] Servei de Radiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Valente F] Servei de Cardiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Centro de Investigación en Red de Enfermedades Cardiovasculares (CIBERCV), Spain. [Ferreira-Gonzalez I] Servei de Cardiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Centro de Investigación en Red de Epidemiología CIBER-ESP, Spain. [Marsal JR] Servei de Cardiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Castro-Alba MA, Sureda-Barbosa C] Servei de Cirurgia Cardíaca, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Subirana-Domènech MT] Unitat Integrada de Cardiopaties Congènites de l’Adolescent i l’Adult, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Hospital Sant Pau, Barcelona, Spain. Department of Cardiology, Hospital Universitari Santa Creu I Sant Pau, Barcelona, Spain. [Casaldàliga-Ferrer J] Unitat Integrada de Cardiopaties Congènites de l’Adolescent i l’Adult, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Hospital Sant Pau, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Circulatory and Respiratory Physiological Phenomena::Cardiovascular Physiological Phenomena::Myocardial Contraction::Diastole [PHENOMENA AND PROCESSES], diagnóstico::técnicas y procedimientos diagnósticos::diagnóstico por imagen::técnicas de imagen cardíaca::ecocardiografía [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], enfermedades cardiovasculares::enfermedades cardíacas::disfunción ventricular::disfunción ventricular derecha [ENFERMEDADES], fenómenos fisiológicos respiratorios y circulatorios::fenómenos fisiológicos cardiovasculares::contracción miocárdica::diástole [FENÓMENOS Y PROCESOS], Cardiopatia congènita, Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Imaging::Cardiac Imaging Techniques::Echocardiography [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Cardiovascular Diseases::Heart Diseases::Ventricular Dysfunction::Ventricular Dysfunction, Right [DISEASES], General Medicine, intervenciones quirúrgicas::procedimientos quirúrgicos cardiovasculares::procedimientos quirúrgicos cardíacos [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Diàstole cardíaca, Surgical Procedures, Operative::Cardiovascular Surgical Procedures::Cardiac Surgical Procedures [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Ecocardiografia
Abstract: Right diastolic dysfunction; Right atrium function; Restrictive physiology Disfunción diastólica derecha; Función de la aurícula derecha; Fisiología restrictiva Disfunció diastòlica dreta; Funció de l'aurícula dreta; Fisiologia restrictiva Right ventricular (RV) diastolic dysfunction in patients with a surgically-repaired RV outflow tract (RVOT) obstruction merits further studies. Right atrial (RA) dilation and function may be related to (RV) diastolic dysfunction in this setting. The end-diastolic forward flow (EDFF) in the pulmonary artery (PA) has been suggested as a non-invasive marker of poor RV compliance, however, there is controversy regarding its true significance; EDFF quantification may help elucidate this controversy. Objective to study predictors of RA enlargement and dysfunction in patients with a surgically-repaired RVOT obstruction and its relationship with quantitative EDFF. Methods In 81 consecutive patients (mean age: 37.5 (±7) years), transthoracic echocardiography (Echo) and cardiac magnetic resonance (CMR) were performed. Echo parameters: RA size (indexed RA area (iRAA)), RA function (RA global strain (RAGS)) and maximum EDFF velocity-time integral (VTI-EDFF) obtained during a whole respiratory cycle. CMR-indexed RA area (imRAA) was also obtained. Patients were divided into three groups according to iRAA, imRAA and RAGS; bivariate analysis was performed. A multivariate model was then applied using variables that were found to be statistically significant in the bivariate analysis. Results Upon multivariate analysis, higher VTI-EDFF values and the presence of significant tricuspid regurgitation proved to be independent factors associated with increased iRAA and imRAA and lower RAGS, whereas RV volumes, function and pulmonary regurgitant fraction were not. Conclusion VTI-EDFF linearly correlated with the degree of RA dilation and deformation; EDFF quantification as against qualitative assessment may be considered a non-invasive tool for diastolic RV dysfunction.
Published: 2023

9. Nutritional Modulation of Associations between Prenatal Exposure to Persistent Organic Pollutants and Childhood Obesity: A Prospective Cohort Study

Author: German Cano-Sancho, Charline Warembourg, Nuria Güil, Nikos Stratakis, Aitana Lertxundi, Amaia Irizar, Sabrina Llop, Maria-Jose Lopez-Espinosa, Xavier Basagaña, Juan Ramon González, Xavier Coumoul, Sílvia Fernández-Barrés, Jean-Philippe Antignac, Martine Vrijheid, Maribel Casas, Laboratoire d'étude des Résidus et Contaminants dans les Aliments (LABERCA), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), EHESP-Irset (EHESP-Irset), École des Hautes Études en Santé Publique [EHESP] (EHESP), Barcelona Institute for Global Health [Barcelona, Spain] (ISGlobal), and University of Barcelona-Hospital Clinic [Barcelona, Spain]
Subjects: Obesitat en els infants, Fetus -- Nutrició, Embaràs -- Aspectes nutricionals, Health, Toxicology and Mutagenesis, [SDE]Environmental Sciences, Public Health, Environmental and Occupational Health
Abstract: Includes supplementary materials for the online appendix. Prenatal exposure to persistent organic pollutants (POPs) may contribute to the development of childhood obesity and metabolic disorders. However, little is known about whether the maternal nutritional status during pregnancy can modulate these associations. The main objective was to characterize the joint associations and interactions between prenatal levels of POPs and nutrients on childhood obesity. We used data from to the Spanish INfancia y Medio Ambiente–Environment and Childhood (INMA) birth cohort, on POPs and nutritional biomarkers measured in maternal blood collected at the first trimester of pregnancy and child anthropometric measurements at 7 years of age. Six organochlorine compounds (OCs) [dichlorodiphenyldichloroethylene, hexachlorobenzene (HCB), lowercase beta-hexachlorocyclohexaneβ−hexachlorocyclohexane (lowercase beta-uppercase c hβ−HCH) and polychlorinated biphenyls 138, 153, 180] and four per- and polyfluoroalkyl substances (PFAS) were measured. Nutrients included vitamins (D, B12, and folate), polyunsaturated fatty acids (PUFAs), and dietary carotenoids. Two POPs–nutrients mixtures data sets were established: a) OCs, PFAS, vitamins, and carotenoids (lowercase italic n equals 660n=660), and b) OCs, PUFAs, and vitamins (lowercase italic n equals 558n=558). Joint associations of mixtures on obesity were characterized using Bayesian kernel machine regression (BKMR). Relative importance of biomarkers and two-way interactions were identified using gradient boosting machine, hierarchical group lasso regularization, and BKMR. Interactions were further characterized using multivariate regression models in the multiplicative and additive scale. Forty percent of children had overweight or obesity. We observed a positive overall joint association of both POPs–nutrients mixtures on overweight/obesity risk, with HCB and vitamin B12 the biomarkers contributing the most. Recurrent interactions were found between HCB and vitamin B12 across screening models. Relative risk for a natural log increase of HCB was 1.31 (95% CI: 1.11, 1.54, lowercase italic p begin subscript interaction end subscript equals 0.02pInteraction=0.02) in the tertile 2 of vitamin B12 and in the additive scale a relative excess risk due to interaction of 0.11 (95% CI: 0.02, 0.20) was found. Interaction between perfluorooctane sulfonate and lowercase beta-cryptoxanthinβ−cryptoxanthin suggested a protective effect of the antioxidant on overweight/obesity risk. These results support that maternal nutritional status may modulate the effect of prenatal exposure to POPs on childhood overweight/obesity. These findings may help to develop a biological hypothesis for future toxicological studies and to better interpret inconsistent findings in epidemiological studies. https://doi.org/10.1289/EHP11258 We thank all study participants for their generous collaboration. This project has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement no. 874583, the ATHLETE project, and no. 825712, the OBERON project. This publication reflects only the authors’ view and the European Commission is not responsible for any use that may be made of the information it contains. INMA-Sabadell: This study was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; PI041436; PI081151 incl. FEDER funds), CIBERESP, Generalitat de Catalunya-CIRIT 1999SGR 00241, Generalitat de Catalunya-AGAUR 2009 SGR 501, and Fundació La Marató de TV3 (090430). M.C. holds a Miguel Servet fellowship (CP16/00128) funded by Instituto de Salud Carlos III and co-funded by European Social Fund “Investing in your future.” N.S. has received funding from the Ministry of Science and Innovation and State Research Agency through the Centro de Excelencia Severo Ochoa 2019–2023 program (CEX2018-000806-S) and from IJC2020-043630-I financed by MCIN/AEI/10.13039/501100011033 and the European Union NextGenerationEU/PRTR. We also acknowledge support from the Generalitat de Catalunya through the CERCA Program. INMA-Gipuzkoa: This study was funded by grants from Instituto de Salud Carlos III (FIS-PI13/02187 and FIS-PI18/01142 incl. FEDER funds), CIBERESP, Department of Health of the Basque Government (2015111065), and the Provincial Government of Gipuzkoa (DFG15/221) and annual agreements with the municipalities of the study area (Zumarraga, Urretxu, Legazpi, Azkoitia y Azpeitia y Beasain). INMA-Valencia: This study was funded by grants from the UE (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1), Spain: ISCIII (G03/176; FIS-FEDER: PI11/01007, PI11/02591, PI11/02038, PI12/00610, PI13/1944, PI13/2032, PI14/00891, PI14/01687, PI16/1288, and PI17/00663; Miguel Servet-FEDER MS11/00178, MS15/00025, and MSII16/00051), Generalitat Valenciana: FISABIO (UGP 15-230, UGP-15-244, and UGP-15-249), and the Alicia Koplowitz Foundation 2017.
Published: 2023

10. Validation of an autonomous artificial intelligence–based diagnostic system for holistic maculopathy screening in a routine occupational health checkup context

Author: Octavi Font, Jordina Torrents-Barrena, Dídac Royo, Sandra Banderas García, Javier Zarranz-Ventura, Anniken Bures, Cecilia Salinas, Miguel Ángel Zapata, Institut Català de la Salut, [Font O, Royo D] Optretina Image Reading Team, Barcelona, Spain. [Torrents-Barrena J] BCN MedTech, Department of Information and Communication Technologies, Universitat Pompeu Fabra, Barcelona, Spain. [Banderas García S] Facultat de Cirurgia i Ciències Morfològiques, Universitat Autònoma de Barcelona, Bellaterra, Spain. Servei d’Oftalmologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Zarranz-Ventura J] Institut Clinic of Ophthalmology (ICOF), Hospital Clinic, Barcelona, Spain. Institut d’Investigacions Biomediques August Pi I Sunyer (IDIBAPS), Barcelona, Spain. [Bures A, Salinas C] Optretina Image Reading Team, Barcelona, Spain. Instituto de Microcirugía Ocular (IMO), Barcelona, Spain. [Zapata MA] Optretina Image Reading Team, Barcelona, Spain. Servei d’Oftalmologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Otros calificadores::/diagnóstico [Otros calificadores], Macular Degeneration, Cellular and Molecular Neuroscience, Artificial Intelligence, Diabetic retinopathy, Optic Nerve Diseases, Photography, Other subheadings::/diagnosis [Other subheadings], Humans, Eye Diseases::Retinal Diseases [DISEASES], Nevus, Occupational Health, Retrospective Studies, Information Science::Computing Methodologies::Algorithms::Artificial Intelligence [INFORMATION SCIENCE], Diabetic Retinopathy, Retina - Malalties - Diagnòstic, Retinography, Age-related macular degeneration, Intel·ligència artificial, Glaucoma, Ciencias de la información::metodologías computacionales::algoritmos::inteligencia artificial [CIENCIA DE LA INFORMACIÓN], Sensory Systems, Ophthalmology, oftalmopatías::enfermedades de la retina [ENFERMEDADES], ROC Curve, Screening, Artifcial intelligence
Abstract: Purpose This study aims to evaluate the ability of an autonomous artificial intelligence (AI) system for detection of the most common central retinal pathologies in fundus photography. Methods Retrospective diagnostic test evaluation on a raw dataset of 5918 images (2839 individuals) evaluated with non-mydriatic cameras during routine occupational health checkups. Three camera models were employed: Optomed Aurora (field of view — FOV 50º, 88% of the dataset), ZEISS VISUSCOUT 100 (FOV 40º, 9%), and Optomed SmartScope M5 (FOV 40º, 3%). Image acquisition took 2 min per patient. Ground truth for each image of the dataset was determined by 2 masked retina specialists, and disagreements were resolved by a 3rd retina specialist. The specific pathologies considered for evaluation were “diabetic retinopathy” (DR), “Age-related macular degeneration” (AMD), “glaucomatous optic neuropathy” (GON), and “Nevus.” Images with maculopathy signs that did not match the described taxonomy were classified as “Other.” Results The combination of algorithms to detect any abnormalities had an area under the curve (AUC) of 0.963 with a sensitivity of 92.9% and a specificity of 86.8%. The algorithms individually obtained are as follows: AMD AUC 0.980 (sensitivity 93.8%; specificity 95.7%), DR AUC 0.950 (sensitivity 81.1%; specificity 94.8%), GON AUC 0.889 (sensitivity 53.6% specificity 95.7%), Nevus AUC 0.931 (sensitivity 86.7%; specificity 90.7%). Conclusion Our holistic AI approach reaches high diagnostic accuracy at simultaneous detection of DR, AMD, and Nevus. The integration of pathology-specific algorithms permits higher sensitivities with minimal impact on its specificity. It also reduces the risk of missing incidental findings. Deep learning may facilitate wider screenings of eye diseases.
Published: 2022

11. The probability of receiving a kidney transplantation in end-stage kidney disease patients who are treated with haemodiafiltration or haemodialysis: a pooled individual participant data from four randomised controlled trials

Author: Mark Woodward, Way Law, Bernard Canaud, Michiel L. Bots, Marion Morena, Francisco Maduell, Francesco Locatelli, Muriel P.C. Grooteman, Peter J. Blankestijn, Sanne A.E. Peters, Ercan Ok, Andrew Davenport, Ferran Torres, Robin W.M. Vernooij, Menso J. Nubé, Fatih Kircelli, MORNET, Dominique, University Medical Center [Utrecht], Université de Montpellier (UM), Royal Free Hospital [London, UK], VU University Medical Center [Amsterdam], Ege University - EGE (Izmir, Turkey), Alessandro Manzoni Hospital, Hospital Clinic [Barcelona, Spain], Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Vrije Universiteit Amsterdam [Amsterdam] (VU), Universitat Autònoma de Barcelona (UAB), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Imperial College London, University of New South Wales [Sydney] (UNSW), Nephrology, ACS - Diabetes & metabolism, Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Ege Üniversitesi
Subjects: Male, Nephrology, medicine.medical_specialty, medicine.medical_treatment, 030232 urology & nephrology, Hemodiafiltration, lcsh:RC870-923, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Renal Dialysis, Internal medicine, Diabetes mellitus, Humans, Medicine, 030212 general & internal medicine, Kidney transplantation, Dialysis, Aged, Randomized Controlled Trials as Topic, Aged, 80 and over, Body surface area, Creatinine, business.industry, Proportional hazards model, Hazard ratio, Middle Aged, medicine.disease, lcsh:Diseases of the genitourinary system. Urology, Kidney Transplantation, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 3. Good health, chemistry, [No Keyword], [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Kidney Failure, Chronic, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Research Article
Abstract: BackgroundDue to a critical shortage of available kidney grafts, most patients with Stage 5 Chronic Kidney Disease (CKD5) require bridging dialysis support. It remains unclear whether treatment by different dialysis modalities changes the selection and/or preparation of a potential transplant candidate. Therefore, we assessed whether the likelihood of receiving kidney transplant (both living or deceased kidney donors) differs between haemodialysis (HD) and online haemodiafiltration (HDF) in patients with CKD5D.MethodsIndividual participant data from four randomised controlled trials comparing online HDF with HD were used. Information on kidney transplant was obtained during follow-up. The likelihood of receiving a kidney transplant was compared between HD and HDF, and evaluated across different subgroups: age, sex, diabetes, history of cardiovascular disease, albumin, dialysis vintage, fistula, and level of convection volume standardized to body surface area. Hazard ratios (HRs), with corresponding 95% confidence intervals (95% CI), comparing the effect of online HDF versus HD on the likelihood of receiving a kidney transplant, were estimated using Cox proportional hazards models with a random effect for study.ResultsAfter a median follow-up of 2.5years (Q1 to Q3: 1.9-3.0), 331 of the 1620 (20.4%) patients with CKD5D received a kidney transplant. This concerned 22% (n=179) of patients who were treated with online HDF compared with 19% (n=152) of patients who were treated with HD. No differences in the likelihood of undergoing a kidney transplant were found between the two dialysis modalities in both the crude analyse (HR: 1.07, 95% CI: 0.86-1.33) and adjusted analysis for age, sex, diabetes, cardiovascular history, albumin, and creatinine (HR: 1.15, 95%-CI: 0.92-1.44). There was no evidence for a differential effect across subgroups based on patient- and disease-characteristics nor in different categories of convection volumes.ConclusionsTreatment with HD and HDF does not affect the selection and/or preparation of CKD5D patients for kidney transplant given that the likelihood of receiving a kidney transplant does not differ between the dialysis modalities. These finding persisted across a variety of subgroups differing in patient and disease characteristics and is not affected by the level of convection volume delivered during HDF treatment sessions., CONVINCE study (European Union's Horizon 2020 research and innovation programme) [754803], Funding details are listed in Appendix 4. RWMV, PJB, and MLB are funded by the CONVINCE study (European Union's Horizon 2020 research and innovation programme under grant agreement No 754803).
Published: 2021

12. Skin manifestations of COVID‐19 in children: Part 2

Author: C Luca, V Zawar, D van Gysel, M Casals, Angela Hernández-Martín, Annabel Maruani, E Bonifazi, Christine Bodemer, F Mazzotta, T Hubiche, Ramon Grimalt, Isabel Colmenero, A Belloni-Fortina, L Martos-Cabrera, David Andina, I Grozdev, Suzanne G.M.A. Pasmans, A Chiriac, Antonio Torrelo, M P Novoa, M A Morren, M Munisami, Hagen Ott, Carmen Salavastru, Veronica A. Kinsler, A Nanda, M El-Hachem, Andrea Diociaiuti, J Ferrando, L Fertitta, A D Akkaya, Dermatology, Hospital Infantil Universitario Niño Jesús [Madrid, Spain] (HIUNJ), University of Padua [Italy], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Bambino Gesù Children’s Hospital [Rome, Italy], Onze Lieve Vrouw Hospital, Université Côte d'Azur (UCA), MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hospital Universitari Parc Taulí of Sabadell, Barcelona, Hospital Clinic [Barcelona, Spain], Universitat Internacional de Catalunya [Barcelona] (UIC), Children's University Hospital Queen Fabiola [Bruxelles, Belgium], Great Ormond Street Hospital for Children [London] (GOSH), University of Lausanne (UNIL), Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Children's Hospital 'Auf der Bult', Eramus MC-Sophia Children’s Hospital, Partenaires INRAE, University of Medicine and Pharmacy 'Carol Davila' Bucharest (UMPCD), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)
Subjects: 2019-20 coronavirus outbreak, medicine.medical_specialty, Adolescent, Urticaria, Coronavirus disease 2019 (COVID-19), [SDV]Life Sciences [q-bio], Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Dermatology, Mucocutaneous Lymph Node Syndrome, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Correspondence, Pandemic, medicine, Humans, Erythema multiforme, Child, skin and connective tissue diseases, ComputingMilieux_MISCELLANEOUS, Erythema Multiforme, Skin manifestations, Respiratory distress, SARS-CoV-2, business.industry, COVID-19, Exanthema, medicine.disease, Erythema Multiforme/pathology, Letter To The Editor, Urticaria/pathology, 3. Good health, 030220 oncology & carcinogenesis, Mucocutaneous Lymph Node Syndrome/virology, COVID-19/complications, Presentation (obstetrics), business, Exanthema/pathology
Abstract: The current COVID-19 pandemic is caused by the SARS-CoV-2 coronavirus. The initial recognized symptoms were respiratory, sometimes culminating in severe respiratory distress requiring ventilation, and causing death in a percentage of those infected. As time has passed, other symptoms have been recognized. The initial reports of cutaneous manifestations were from Italian dermatologists, probably because Italy was the first European country to be heavily affected by the pandemic. The overall clinical presentation, course and outcome of SARS-CoV-2 infection in children differ from those in adults, as do the cutaneous manifestations of childhood. In this review, we summarize the current knowledge on the cutaneous manifestations of COVID-19 in children after thorough and critical review of articles published in the literature and from the personal experience of a large panel of paediatric dermatologists in Europe. In Part 1, we discussed one of the first and most widespread cutaneous manifestations of COVID-19, chilblain-like lesions. In this part of the review, we describe other manifestations, including erythema multiforme, urticaria and Kawasaki disease-like inflammatory multisystemic syndrome. In Part 3, we discuss the histological findings of COVID-19 manifestations, and the testing and management of infected children for both COVID-19 and any other pre-existing conditions.
Published: 2020

13. Recomendaciones en el manejo de la pandemia por coronavirus SARS-CoV-2 (Covid-19) en pacientes con trasplante renal

Author: López, Verónica, Vázquez, Teresa, Alonso-Titos, Juana, Cabello, Mercedes, Alonso, Angel, Beneyto, Isabel, Crespo, Marta, Díaz-Corte, Carmen, Franco, Antonio, González-Roncero, Francisco, Gutiérrez, Elena, Guirado, Luis, Jiménez, Carlos, Jironda, Cristina, Lauzurica, Ricardo, Llorente, Santiago, Mazuecos, Auxiliadora, Paul, Javier, Rodríguez-Benot, Alberto, Ruiz, Juan Carlos, Sánchez-Fructuoso, Ana, Sola, Eugenia, Torregrosa, Vicente, Zárraga, Sofía, Hernández, Domingo, Grupo de Estudio GREAT, Grupo de Estudio GREAT (Grupo Español de Actualizaciones en Trasplante), [López,V, Vázquez,T, Alonso-Titos,J, Cabello,M, Gutiérrez,E, Jironda,C, Sola,E, Hernández,D] Unidad de Gestión Clínica de Nefrología, Hospital Regional Universitario de Málaga, Universidad de Málaga, Instituto Biomédico de Investigación de Málaga (IBIMA), REDinREN (RD16/0009/0006), Málaga, Spain. [Alonso,A] Servicio de Nefrologia, Complejo Hospitalario A Coruña, Spain. [Beneyto,I] Servicio de Nefrología, Hospital Universitario Politécnico La Fe, Valencia, Spain. [Crespo,M, Díaz-Corte,C] Servicio de Nefrología, Hospital del Mar, Barcelona, España, Servicio de Nefrología, Hospital Central de Asturias, REDinREN RD16/0009/0021, Asturias, Spain. [Franco,A] Servicio de Nefrología, Hospital de Alicante, Alicante, Spain. [González-Roncero,F] Servicio de Nefrología, Hospital Virgen del Rocío, Sevilla, Spain. [Guirado,L] Servicio de Nefrología, Fundación Puigvert, REDinREN RD16/0009/0019, Barcelona, Spain. [Jiménez,C] Servicio de Nefrología, Hospital La Paz, Madrid, Spain. [Lauzurica,R] Servicio de Nefrología, Hospital Trias i Pujol, REDinREN RD16/0009/0032, Barcelona, Spain. [Llorente,S] Servicio de Nefrología, Hospital Virgen de la Arrixaca, Murcia, Spain. [Mazuecos,A] Servicio de Nefrología, Hospital Universitario Puerta del Mar, Cádiz, Spain. [Paul,J] Servicio de Nefrología, Hospital Miguel Servet, Zaragoza, Spain. [Rodríguez-Benot,A] Servicio de Nefrología, Hospital Reina Sofía, Instituto Maimónides de Investigación Biomédica de Córdoba, Córdoba, Spain. [Ruiz,JC] Servicio de Nefrología, Hospital Marqués de Valdecilla, IDIVAL, REDinREN RD16/0009/0027, Santander, Spain. [Sánchez-Fructuoso,A] Servicio de Nefrología, Hospital Clínico San Carlos, Universidad Complutense de Madrid, Madrid, Spain. [Torregrosa,V] Servicio de Nefrología, Hospital Clinic, Barcelona, Spain. [Zárraga,S] Servicio de Nefrología, Hospital de Cruces, Bilbao, Spain., Este artículo fue financiado en parte por el Ministerio de Economía, Industria y Competitividad de España, del ISCIII (PI17/02043), cofinanciado por el Fondo Europeo de Desarrollo Regional-FEDER, RETIC (REDinREN RED16/0009/0006, RD16/0009/0021, RD16/0009/0019, RD16/0009/0027, and RD16/0009/0032.
Subjects: Phenomena and Processes::Immune System Phenomena::Immunocompromised Host [Medical Subject Headings], Anatomy::Urogenital System::Urinary Tract::Kidney [Medical Subject Headings], Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Population, 030230 surgery, lcsh:RC870-923, medicine.disease_cause, Kidney transplant, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Kidney transplantation, 03 medical and health sciences, 0302 clinical medicine, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Epidemiologic Factors::Comorbidity [Medical Subject Headings], Pandemic, COVID-19, inmunodeprimido, trasplante renal, kidney transplantation, immunosuppressed, SARS-CoV-2, Medicine, Vulnerable population, 030212 general & internal medicine, education, Coronavirus, Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings], education.field_of_study, Inmunodeprimido, business.industry, Health Care::Environment and Public Health::Public Health::Disease Outbreaks::Epidemics::Pandemics [Medical Subject Headings], lcsh:Diseases of the genitourinary system. Urology, medicine.disease, Virology, Diseases::Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [Medical Subject Headings], Trasplante renal, Immunosuppressed, Nephrology, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Immunologic Factors::Immunosuppressive Agents [Medical Subject Headings], Covid-19, business
Abstract: The SARS-CoV-2 (Covid-19) coronavirus pandemic is evolving very quickly and means a special risk for both immunosuppressed and comorbid patients. Knowledge about this growing infection is also increasing although many uncertainties remain, especially in the kidney transplant population. This manuscript presents a proposal for action with general and specific recommendations to protect and prevent infection in this vulnerable population such as kidney transplant recipients. Resumen: La pandemia por coronavirus SARS-CoV-2 (Covid-19) está evolucionando de manera muy rápida y representa un riesgo especial en pacientes inmunodeprimidos y con comorbilidades añadidas. El conocimiento sobre esta infección emergente va también en aumento, si bien, aún sigue habiendo muchas incógnitas, sobre todo en la población con trasplante renal. Este manuscrito presenta una propuesta de actuación con recomendaciones generales y específicas para proteger y prevenir de la infección a esta población tan vulnerable como son los receptores de un trasplante renal.
Published: 2020

14. The Normalization of Violence during Sex among Young Mozambicans Reportedly under the Influence of Pornography

Author: Taylor Sheridan, Germano Vera Cruz, Centre de Recherche en Psychologie : Cognition, Psychisme et Organisations - UR UPJV 7273 (CRP-CPO), Université de Picardie Jules Verne (UPJV), Barcelona Institute for Global Health [Barcelona, Spain] (ISGlobal), and University of Barcelona-Hospital Clinic [Barcelona, Spain]
Subjects: Cultural Studies, [SHS.SOCIO]Humanities and Social Sciences/Sociology, Addiction, media_common.quotation_subject, Psychological intervention, [SHS.PSY]Humanities and Social Sciences/Psychology, Human sexuality, medicine.disease, Gender Studies, Sexual desire, medicine, Pornography, Young adult, Psychology, [SHS.GENRE]Humanities and Social Sciences/Gender studies, Psychosocial, ComputingMilieux_MISCELLANEOUS, media_common, Psychological trauma, Clinical psychology
Abstract: In sub-Saharan Africa, the increase in pornographic video consumption over the past 15 years might be shaping the sexual practices of the new generation. Using a comprehensive approach, the present study aims to first, measure the prevalence of acts of violence during sex reportedly inspired by pornography (VDSIP) among Mozambican adolescents and young adults; second, examine the consequences of these practices on the individuals involved; and third, identify the cognitive and psychosocial mechanisms by which these practices are adopted and normalized. Overall, 105 Mozambicans were interviewed. Participants’ responses were subjected to discourse content and frequency analysis. The results show that, in the 12 months preceding the interview, between 77.6% and 89.2% of male participants performed VDSIP that included inflicting physical or psychological violence on their partners. In the same period, between 8.5% and 16.8% of female participants performed VDSIP that included inflicting physical or psychological violence on their partners. Females (63.1% of them) were shown to be much more affected by the negative consequences (e.g., depression, low self-esteem, physical and psychological trauma) associated with the practice of VDSIP compared to males (17.7% of them). The main mechanisms by which these practices are adopted and normalized were reported to be imitation, reinforcement, desire for recognition, addiction, development of sexual scripts, misunderstanding about women’s sexual desire, gender inequalities, cognitive and psychosocial biases, and manipulation of the partner’ consent. This study’s findings can be used to design tailored education interventions to mitigate the negative effects of violence during sex among African adolescents and young adults.
Published: 2022

15. Placental Tissue Destruction and Insufficiency From COVID-19 Causes Stillbirth and Neonatal Death From Hypoxic-Ischemic Injury : A Study of 68 Cases With SARS-CoV-2 Placentitis From 12 Countries

Author: Schwartz, David A., Avvad-Portari, Elyzabeth, Babal, Pavel, Baldewijns, Marcella, Blomberg, Marie, Bouachba, Amine, Camacho, Jessica, Collardeau-Frachon, Sophie, Colson, Arthur, Dehaene, Isabelle, Ferreres, Joan Carles, Fitzgerald, Brendan, Garrido-Pontnou, Marta, Gergis, Hazem, Hargitai, Beata, Cecilia Helguera-Repetto, A., Holmstrom, Sandra, Irles, Claudine Liliane, Leijonhfvud, Asa, Libbrecht, Sasha, Marton, Tamas, McEntagart, Noel, Molina, James T., Morotti, Raffaella, Nadal, Alfons, Navarro, Alexandra, Nelander, Maria, Oviedo, Angelica, Otani, Andre Ricardo Oyamada, Papadogiannakis, Nikos, Petersen, Astrid C., Roberts, Drucilla J., Saad, Ali G., Sand, Anna, Schoenmakers, Sam, Sehn, Jennifer K., Simpson, Preston R., Thomas, Kristen, Yolotzin Valdespino-Vazquez, M., Van der Meeren, Lotte E., Van Dorpe, Jo, Verdijk, Robert M., Watkins, Jaclyn C., Zaigham, Mehreen, Augusta University - Medical College of Georgia, University System of Georgia (USG), Fernandes Figueira Institute [Rio de Janeiro, Brazil] (2FI), Comenius University in Bratislava, University Hospitals Leuven [Leuven], Linköping University (LIU), Hospices Civils de Lyon (HCL), Société Française de Foetopathologie [Paris] (SOFFOET), Vall d'Hebron University Hospital [Barcelona], Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain = Catholic University of Louvain (UCL), Ghent University Hospital, Hospital Universitari Parc Taulí de Sabadell [Barcelona, Spain] (HUPTS), Universitat Autònoma de Barcelona (UAB), University College Cork (UCC), Doncaster and Bassetlaw Teaching Hospitals NHS Foundation Trust [Doncaster, UK] (DBTH), Birmingham Women's and Children's NHS Foundation Trust, National Institute of Perinatology [Mexico City, Mexico] (NIP), Halland Hospital [Varberg, Sweden] (2H), National Institute of Perinatology 'Isidro Espinosa de los Reyes' [Mexico City, Mexico] (NIP-IER), Hôpital de Helsingborg [Lund, Sweden] (2H), Lund University [Lund], Antwerp University Hospital [Edegem] (UZA), Rotunda Hospital [Dublin, Republic of Ireland] (RH), Beaumont Pathology Associates [Beaumont, TX, USA] (BPA), Department of Neuroscience, Yale University School of Medicine, Yale School of Medicine [New Haven, Connecticut] (YSM), Hospital Clinic [Barcelona, Spain], Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Uppsala University, Burrell College of Osteopathic Medicine [Las Cruces, New Mexico] (BCOM), Laboratório Ferdinando Costa [São Paulo, Brazil] (LFC), Karolinska University Hospital [Stockholm], Aalborg University [Denmark] (AAU), Massachusetts General Hospital [Boston], Harvard Medical School [Boston] (HMS), University of Miami Leonard M. Miller School of Medicine (UMMSM), Karolinska Institute, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), CHRISTUS Hospital St Elizabeth [Beaumont, TX, USA] (CHRISTUS HSE), New York University Langone Medical Center (NYU Langone Medical Center), NYU System (NYU), Leiden University Medical Center (LUMC), University Medical Center [Utrecht], Skane University Hospital [Lund], Skane University Hospital [Malmo], CarMeN, laboratoire, and Obstetrics & Gynecology
Subjects: Fibrin, Pregnancy Complications, Infectious/mortality, Infectious Medicine, SARS-CoV-2, [SDV]Life Sciences [q-bio], Infant, Newborn, Infektionsmedicin, Placenta/pathology, Stillbirth, Infectious Disease Transmission, Vertical, [SDV] Life Sciences [q-bio], Pregnancy, Perinatal Death/etiology, COVID-19/complications, Humans, Female, Hypoxia/pathology, Retrospective Studies
Abstract: CONTEXT.—: Perinatal death is an increasingly important problem as the coronavirus disease 2019 (COVID-19) pandemic continues, but the mechanism of death has been unclear.OBJECTIVE.—: To evaluate the role of the placenta in causing stillbirth and neonatal death following maternal infection with COVID-19 and confirmed placental positivity for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).DESIGN.—: Case-based retrospective clinicopathologic analysis by a multinational group of 44 perinatal specialists from 12 countries of placental and autopsy pathology findings from 64 stillborns and 4 neonatal deaths having placentas testing positive for SARS-CoV-2 following delivery to mothers with COVID-19.RESULTS.—: Of the 3 findings constituting SARS-CoV-2 placentitis, all 68 placentas had increased fibrin deposition and villous trophoblast necrosis and 66 had chronic histiocytic intervillositis. Sixty-three placentas had massive perivillous fibrin deposition. Severe destructive placental disease from SARS-CoV-2 placentitis averaged 77.7% tissue involvement. Other findings included multiple intervillous thrombi (37%; 25 of 68) and chronic villitis (32%; 22 of 68). The majority (19; 63%) of the 30 autopsies revealed no significant fetal abnormalities except for intrauterine hypoxia and asphyxia. Among all 68 cases, SARS-CoV-2 was detected from a body specimen in 16 of 28 cases tested, most frequently from nasopharyngeal swabs. Four autopsied stillborns had SARS-CoV-2 identified in internal organs.CONCLUSIONS.—: The pathology abnormalities composing SARS-CoV-2 placentitis cause widespread and severe placental destruction resulting in placental malperfusion and insufficiency. In these cases, intrauterine and perinatal death likely results directly from placental insufficiency and fetal hypoxic-ischemic injury. There was no evidence that SARS-CoV-2 involvement of the fetus had a role in causing these deaths.
Published: 2022

16. European Association of Cardiothoracic Anesthesiology and Intensive Care Pediatric Cardiac Anesthesia Fellowship Curriculum: First Edition

Author: Ricard Navarro-Ripoll, Marc Vives, Steffen Rex, P. Matute, R. Peter Alston, Theofili Kousi, Simon J. Howell, Mona Momeni, Hossam El-Ashmawi, Fawzia Aboulfetouh, M. Granell, Aniruddha R. Janai, Gabor Erdoes, Caetano Nigro Neto, Alberto Hernandez Martinez, Sascha Treskatsch, Gianluca Paternoster, Theofani Antoniou, Anna Flo Forner, Kirstin Wilkinson, Giovanni Landoni, Joost M.A.A. van der Maaten, Joachim Erb, Philippe Gaudard, Philippe Burtin, E Schindler, Andrea Székely, Alain Vuylsteke, Laszlo L. Szegedi, Vera von Dossow, Jens Fassl, Chirojit Mukherjee, Mohamed R. El-Tahan, Fabio Guarracino, Dominique Bettex, Maria Benedetto, Dieter Van Beersel, Jan-Uwe Schreiber, Patrick Wouters, Dragana Unic-Stojanovic, Mansoura University [Egypt], University of Bern, University Medical Center Groningen [Groningen] (UMCG), University Hospital Southampton NHS Foundation Trust, Onassis Cardiac Surgery Center [Athens] (OCSC), Ruhr University Bochum (RUB), Instituto de Cardiologia Dante Pazzanese (IDPC), University Hospital Bonn, Semmelweis University [Budapest], University of Leipzig [Leipzig, Allemagne], University Department of Fundamental and Applied Medical Sciences and Clinical Department of Anesthesiology and Perioperative Medicine, Ghent, Belgium, Azienda Ospedaliera Universitaria Pisana, Clinique du Millénaire - Oc Santé [Montpellier], Oc Santé [Montpellier], University of Belgrade [Belgrade], Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Hospital Clinic [Barcelona, Spain], Misr University for Science & Technology (MUST), Technische Universität Dresden = Dresden University of Technology (TU Dresden), University hospital of Zurich [Zurich], Sant'Orsola-Malpighi Hospital [Bologna, Italy], Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Royal Infirmary of Edinburgh, IRCCS San Raffaele Scientific Institute [Milan, Italie], University General Hospital of Valencia, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Charité Campus Benjamin Franklin, University Hospitals Leuven [Leuven], Royal Papworth Hospital, Cambridge Biomedical Campus, Cambridge, United Kingdom., University of Leeds, Hospital Universitario de Bellvitge, University Hospital Basel [Basel], Hospital Dr Josep Trueta, Cairo University, Department of Anesthesia & Intensive Care, Helios Clinic for Cardiac Surgery, Karlsruhe, Germany., Hospital Clinico San Carlos, Hospital Clínico San Carlos, Cliniques Universitaires Saint-Luc [Bruxelles], Université Catholique de Louvain = Catholic University of Louvain (UCL), UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, UCL - (SLuc) Service d'anesthésiologie, El-Tahan, M. R., Erdoes, G., van der Maaten, J., Wilkinson, K., Kousi, T., Antoniou, T., von Dossow, V., Neto, C. N., Schindler, E., Szekely, A., Forner, A. F., Wouters, P. F., Guarracino, F., Burtin, P., Unic-Stojanovic, D., Schreiber, J. -U., Matute, P., Aboulfetouh, F., Navarro-Ripoll, R., Fassl, J., Bettex, D., Benedetto, M., Szegedi, L., Alston, R. P., Landoni, G., Granell, M., Gaudard, P., Treskatsch, S., Van Beersel, D., Vuylsteke, A., Howell, S., Janai, A. R., Martinez, A. H., Erb, J. M., Vives, M., El-Ashmawi, H., Rex, S., Mukherjee, C., Paternoster, G., Momeni, M., MUMC+: MA Anesthesiologie (9), and RS: MHeNs - R3 - Neuroscience
Subjects: medicine.medical_specialty, Critical Care, [SDV]Life Sciences [q-bio], education, MEDLINE, Subspecialty, 03 medical and health sciences, 0302 clinical medicine, 030202 anesthesiology, Pediatric anesthesiology, Anesthesiology, Intensive care, Anesthesia, Cardiac Procedures, Medicine, Humans, Fellowships and Scholarships, 610 Medicine & health, Child, Curriculum, Cardiothoracic anesthesiology, business.industry, General surgery, 030208 emergency & critical care medicine, 3. Good health, Cardiac Anesthesia, Anesthesiology and Pain Medicine, Perioperative care, cardiovascular system, Cardiology and Cardiovascular Medicine, business
Abstract: International audience; Pediatric cardiac anesthesia is a subspecialty of cardiac and pediatric anesthesiology dedicated to the perioperative care of patients with congenital heart disease. Members of the Congenital and Education Subcommittees of the European Association of Cardiothoracic Anaesthesiology and Intensive Care (EACTAIC) agreed on the necessity to develop an EACTAIC pediatric cardiac anesthesia fellowship curriculum. This manuscript represents a consensus on the composition and the design of the EACTAIC Pediatric Cardiac Anesthesia Fellowship program. This curriculum provides a basis for the training of future pediatric cardiac anesthesiologists by clearly defining the theoretical and practical requirements for fellows and host centers.
Published: 2021

17. Case Report: Barely Able to Speak, Can't Stop Echoing: Echolalic Dynamic Aphasia in Progressive Supranuclear Palsy

Author: Marcelo L. Berthier, Florencia Hoet, Álvaro Beltrán-Corbellini, Daniel Santana-Moreno, Lisa Edelkraut, Guadalupe Dávila, [Berthier,ML, Hoet,F, Edelkraut,L, Dávila,G] Cognitive Neurology and Aphasia Unit, Centro de Investigaciones Médico-Sanitarias, University of Malaga, Málaga, Spain, [Berthier,ML, Dávila,G] Research Laboratory on the Neuroscience of Language, Faculty of Psychology and Speech Therapy, University of Malaga, Málaga, Spain. [Berthier,ML, Dávila,G] Instituto de Investigación Biomédica de Málaga – IBIMA, Málaga, Spain. [Hoet,F] Servicio de Otorrinolaringología, Sección Fonoaudiología, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina. [Beltrán-Corbellini,A] Department of Neurology, Hospital Universitario Ramón y Cajal, Madrid, Spain. [Santana-Moreno,D] Department of Neurology, Hospital Clinic, Barcelona, Spain. [Edelkraut,L, Dávila,G] Area of Psychobiology, Faculty of Psychology and Speech Therapy, University of Malaga, Málaga, Spain., and This work was supported in part by the Ministerio de Economía, Industria y Competitividad, Instituto de Salud Carlos III, Madrid, Spain under Grant: PI16/01514. MB has been supported by funds from the European Social Fund (FEDER). LE has been funded by a PhD scholarship from the Spanish Ministry of Science and Innovation and Universities under the FPU program (FPU17/04136).
Subjects: Aging, Echolalia, Diseases::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Basal Ganglia Diseases::Supranuclear Palsy, Progressive [Medical Subject Headings], Phenomena and Processes::Genetic Phenomena::Phenotype [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Imaging::Magnetic Resonance Imaging [Medical Subject Headings], Case Report, Audiology, Diseases::Nervous System Diseases::Neurologic Manifestations::Neurobehavioral Manifestations::Psychomotor Disorders::Apraxias [Medical Subject Headings], Apraxia, Primary progressive aphasia, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Ecolalia, Parálisis supranuclear progresiva, Afasia, Apathy, Persons::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Diseases::Nervous System Diseases::Neurologic Manifestations::Neurobehavioral Manifestations::Communication Disorders::Language Disorders::Speech Disorders::Echolalia [Medical Subject Headings], Psychiatry and Psychology::Behavior and Behavior Mechanisms::Emotions::Apathy [Medical Subject Headings], Psychiatry and Psychology::Psychological Phenomena and Processes::Mental Processes::Cognition::Comprehension [Medical Subject Headings], 05 social sciences, Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Neurologic Manifestations::Neurobehavioral Manifestations::Communication Disorders::Language Disorders::Speech Disorders::Aphasia::Aphasia, Primary Progressive [Medical Subject Headings], Afasia progresiva primaria, Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Neurologic Manifestations::Neurobehavioral Manifestations::Communication Disorders::Language Disorders::Speech Disorders::Aphasia [Medical Subject Headings], dynamic aphasia, Frontal lobe, Diseases::Pathological Conditions, Signs and Symptoms::Pathological Conditions, Anatomical::Atrophy [Medical Subject Headings], Anatomy::Nervous System::Central Nervous System::Brain::Prosencephalon::Telencephalon::Cerebrum::Basal Ganglia::Corpus Striatum::Neostriatum::Caudate Nucleus [Medical Subject Headings], medicine.symptom, Psychology, Comprehension, Dynamic aphasia, RC321-571, Anatomy::Nervous System::Central Nervous System::Brain::Prosencephalon::Telencephalon::Cerebrum::Cerebral Cortex::Frontal Lobe [Medical Subject Headings], medicine.medical_specialty, Cognitive Neuroscience, Apatía, Neurosciences. Biological psychiatry. Neuropsychiatry, Disciplines and Occupations::Health Occupations::Allied Health Occupations::Speech-Language Pathology [Medical Subject Headings], behavioral disciplines and activities, 050105 experimental psychology, Progressive supranuclear palsy, 03 medical and health sciences, Aphasia, medicine, echolalia, 0501 psychology and cognitive sciences, Inhibition deficits, Patología del habla y lenguaje, Comprensión, progressive supranuclear palsy, medicine.disease, Anatomy::Nervous System::Central Nervous System::Brain::Brain Stem::Mesencephalon::Tegmentum Mesencephali [Medical Subject Headings], Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Communication::Verbal Behavior::Speech [Medical Subject Headings], inhibition deficits, Atrofia, Psychiatry and Psychology::Behavioral Disciplines and Activities::Psychological Tests::Neuropsychological Tests [Medical Subject Headings], primary progressive aphasia, Midbrain tegmentum, Atrophy, 030217 neurology & neurosurgery, Neuroscience, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Imaging::Neuroimaging [Medical Subject Headings]
Abstract: The diagnostic criteria for progressive supranuclear palsy (PSP) incorporate two speech-language disturbances (SLDs), non-fluent/agrammatic primary progressive aphasia and progressive apraxia of speech, but overlook the inclusion of other SLDs, including dynamic aphasia (DA). Thus, there is a need to reappraise the broad spectrum of SLDs in PSP to include other presenting phenotypes. Here we report findings from the study of two elderly patients with PSP presenting with DA and irrepressible echolalia. Both patients had markedly impoverished verbal production, but their performance in other tasks (repetition and naming) and auditory comprehension were preserved or only mildly impaired. Experimental tests of DA revealed impaired word and sentence generation in response to verbal and non-verbal stimuli. Additional language and cognitive testing revealed different types of echolalia (mitigated, automatic, and echoing approval) as well as impaired inhibitory control and social cognition (mentalizing). Both patients had negative neuropsychiatric alterations (i.e., apathy, aspontaneity, and indifference/emotional flatness). Brain magnetic resonance imaging in both patients showed atrophy of the midbrain tegmentum and superior medial frontal cortex suggestive of PSP, yet further evaluation of the neural correlates using multimodal neuroimaging and neuropathological data was not performed. However, based on the already known neural basis of DA and echolalia in PSP and stroke, we suggest that, in the present cases, neurodegeneration in the midbrain tegmentum, superior medial frontal lobe, and caudate nucleus was responsible for DA and that decreased activity in these regions may play a permissive role for eliciting verbal echoing via disinhibition of the perisylvian speech-language network.
Published: 2021

18. Personality disorders in the ICD-11: Spanish validation of the PiCD and the SASPD in a mixed community and clinical sample

Author: Juan C. Pascual, Josep M. Peri, Anton Aluja, Gemma Vall, Maria V. Navarro-Haro, Joshua R. Oltmanns, Joaquim Soler, Bárbara Sureda, Marta Torrens, Alfonso Gutiérrez-Zotes, David Gallardo-Pujol, Thomas A. Widiger, Fernando Gutiérrez, Joan Ignasi Mestre-Pintó, Natalia Calvo, Luis F. García, José Arzola Ruiz, Miquel Alabèrnia-Segura, Marc Ferrer, Miguel Gárriz, UAM. Departamento de Psicología Biológica y de la Salud, Institut Català de la Salut, [Gutiérrez F] Hospital Clinic, Barcelona, Spain. IDIBAPS, Barcelona, Spain. [Aluja A] University of Lleida, Lleida, Spain. Biomedical Research Institute of Lleida, Lleida, Spain. [Ruiz J] University of Barcelona, Barcelona, Spain. [García LF] Biomedical Research Institute of Lleida, Lleida, Spain. Autonomous University of Madrid, Madrid, Spain. [Gárriz M] Institut de Neuropsiquiatria i Addiccions, Barcelona, Spain. [Gutiérrez-Zotes A] IISPV-Universitat Rovira i Virgili, Reus, Spain. [Calvo N, Ferrer M] Universitat Autònoma de Barcelona, Bellaterra, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: 050103 clinical psychology, Mental Disorders::Personality Disorders [PSYCHIATRY AND PSYCHOLOGY], Personality Inventory, personality disorder, severity, 050109 social psychology, Ciencias de la información::servicios de información::documentación::Vocabulario controlado::Manual Diagnóstico y Estadístico de los Trastornos Mentales [CIENCIA DE LA INFORMACIÓN], Trastorns de la personalitat, Applied Psychology, media_common, 05 social sciences, Articles, Diagnostic and Statistical Manual of Mental Disorders, Clinical Psychology, PiCD, trastornos mentales::trastornos de la personalidad [PSIQUIATRÍA Y PSICOLOGÍA], Ciencias de la información::servicios de información::documentación::Vocabulario controlado::Clasificación Internacional de Enfermedades [CIENCIA DE LA INFORMACIÓN], Trait, Personality Assessment Inventory, Psychology, Psicometria, Clinical psychology, Personality, personality pathology, Tests de personalitat, Psychometrics, media_common.quotation_subject, Standardized test, Personality Disorders, Negative affectivity, Severity, SASPD, International Classification of Diseases, ICD-11, Taxonomy (general), medicine, Humans, 0501 psychology and cognitive sciences, Personality disorders, Information Science::Information Services::Documentation::Vocabulary, Controlled::Diagnostic and Statistical Manual of Mental Disorders [INFORMATION SCIENCE], Personality disorder, business.industry, Malalties mentals - Classificació, Personality pathology, medicine.disease, Psicología, Personality tests, Information Science::Information Services::Documentation::Vocabulary, Controlled::International Classification of Diseases [INFORMATION SCIENCE], business, Estadística mèdica
Abstract: The International Classification of Diseases–11th revision (ICD-11) classification of personality disorders is the official diagnostic system that is used all over the world, and it has recently been renewed. However, as yet very few data are available on its performance. This study examines the Personality Inventory for ICD-11 (PiCD), which assesses the personality domains of the system, and the Standardized Assessment of Severity of Personality Disorder (SASPD), which determines severity. The Spanish versions of the questionnaires were administered to a community (n = 2,522) and a clinical sample (n = 797). Internal consistency was adequate in the PiCD (α =.75 to.84) but less so in the SASPD (α =.64 and.73). Factor analyses suggested a unidimensional or bidimensional structure for severity, while revealing that the personality trait qualifiers are organized into four factors: negative affectivity, detachment, dissociality, and a bipolar domain of disinhibition–anankastia. The mutual relationships between traits and severity were analyzed, as well as the ability of the whole system to identify clinical subjects. Although further improvements are required, the results generally support the use of the PiCD and the SASPD and help substantiate the new ICD-11 taxonomy that underlies them., This work was supported by project PI15/00536, part of the Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016, financed by the ISCIII Subdirección General de Evaluación and the cofinanced by the European Regional Development Fund (ERDF, “A way to build Europe”; PI: F. Gutiérrez)
Published: 2021

19. Long-term real-world experience with ipilimumab and non-ipilimumab therapies in advanced melanoma: the IMAGE study

Author: Michal Lotem, T. Kim Le, Jane Brokaw, Srividya Kotapati, Ana Arance, Brian Buysse, Jennifer Lord-Bessen, Frank Meiss, Laurent Mortier, Andriy Moshyk, Pippa Corrie, Stéphane Dalle, Ruth E Board, Susan D. Mathias, Kelly Oh, Ralf Gutzmer, Mark R. Middleton, Julie Scotto, Patrick Terheyden, Apollo - University of Cambridge Repository, Hospices Civils de Lyon (HCL), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 (ONCO-THAI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Cambridge University Hospitals NHS Foundation Trust, Cambridge University Hospitals - NHS (CUH), University of Cambridge [UK] (CAM), Hadassah Hebrew University Hospital, The Hebrew University of Jerusalem (HUJ), Hadassah Hebrew University Medical Center [Jerusalem], Royal Preston Hospital [Preston, UK] (RPH), Hospital Clinic [Barcelona, Spain], University of Freiburg [Freiburg], Universität zu Lübeck = University of Lübeck [Lübeck], Medizinische Hochschule Hannover (MHH), Syneos Health [Morrisville, NC, USA] (SH), Bristol-Myers Squibb [Princeton], Health Outcomes Solutions [Winter Park, FL, USA] (HOS), Churchill Hospital [Breast Care Unit], Churchill Hospital Oxford Centre for Haematology, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Universität zu Lübeck [Lübeck], and Malbec, Odile
Subjects: Male, Cancer Research, Skin Neoplasms, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Systemic therapy, 0302 clinical medicine, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Medicine, Overall survival, 030212 general & internal medicine, Prospective Studies, Immune Checkpoint Inhibitors, Melanoma, RC254-282, Aged, 80 and over, education.field_of_study, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Chemoradiotherapy, Middle Aged, Advanced melanoma, 3. Good health, [SDV] Life Sciences [q-bio], Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Cohort, Female, medicine.drug, Research Article, Subsequent therapy, Quality of life, Adult, medicine.medical_specialty, Population, Ipilimumab, Radiosurgery, 03 medical and health sciences, Young Adult, Internal medicine, Genetics, Humans, Adverse effect, education, Aged, Chemotherapy, business.industry, Survival Analysis, Clinical trial, Radiation therapy, Real-world, business, Follow-Up Studies
Abstract: Background Ipilimumab has shown long-term overall survival (OS) in patients with advanced melanoma in clinical trials, but robust real-world evidence is lacking. We present long-term outcomes from the IMAGE study (NCT01511913) in patients receiving ipilimumab and/or non-ipilimumab (any approved treatment other than ipilimumab) systemic therapies. Methods IMAGE was a multinational, prospective, observational study assessing adult patients with advanced melanoma treated with ipilimumab or non-ipilimumab systemic therapies between June 2012 and March 2015 with ≥3 years of follow-up. Adjusted OS curves based on multivariate Cox regression models included covariate effects. Safety and patient-reported outcomes were assessed. Results Among 1356 patients, 1094 (81%) received ipilimumab and 262 (19%) received non-ipilimumab index therapy (systemic therapy [chemotherapy, anti–programmed death 1 antibodies, or BRAF ± MEK inhibitors], radiotherapy, and radiosurgery). In the overall population, median age was 64 years, 60% were male, 78% were from Europe, and 78% had received previous treatment for advanced melanoma. In the ipilimumab-treated cohort, 780 (71%) patients did not receive subsequent therapy (IPI-noOther) and 314 (29%) received subsequent non-ipilimumab therapy (IPI-Other) on study. In the non-ipilimumab–treated cohort, 205 (78%) patients remained on or received other subsequent non-ipilimumab therapy (Other-Other) and 57 (22%) received subsequent ipilimumab therapy (Other-IPI) on study. Among 1151 patients who received ipilimumab at any time during the study (IPI-noOther, IPI-Other, and Other-IPI), 296 (26%) reported CTCAE grade ≥ 3 treatment-related adverse events, most occurring in year 1. Ipilimumab-treated and non-ipilimumab–treated patients who switched therapy (IPI-Other and Other-IPI) had longer OS than those who did not switch (IPI-noOther and Other-Other). Patients with prior therapy who did not switch therapy (IPI-noOther and Other-Other) showed similar OS. In treatment-naive patients, those in the IPI-noOther group tended to have longer OS than those in the Other-Other group. Patient-reported outcomes were similar between treatment cohorts. Conclusions With long-term follow-up (≥ 3 years), safety and OS in this real-world population of patients treated with ipilimumab 3 mg/kg were consistent with those reported in clinical trials. Patient-reported quality of life was maintained over the study period. OS analysis across both pretreated and treatment-naive patients suggested a beneficial role of ipilimumab early in treatment. Trial registration ClinicalTrials.gov, NCT01511913. Registered January 19, 2012 – Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT01511913
Published: 2021

20. SARS-CoV-2 infection in patients with primary Sjögren syndrome: characterization and outcomes of 51 patients

Author: Brito-Zerón, Pilar, Melchor, Sheila, Seror, Raphaèle, Priori, Roberta, Solans, Roser, Kostov, Belchin, Baldini, Chiara, Carubbi, Francesco, Callejas, Jose Luis, Guisado-Vasco, Pablo, Hernández-Molina, Gabriela, Pasoto, Sandra G, Valim, Valeria, Sisó-Almirall, Antoni, Mariette, Xavier, Carreira, Patricia, Ramos-Casals, Manuel, Brito-Zerón, P, Morcillo, C, Flores-Chávez, A, Ramos-Casals, M, Acar-Denizli, N, Horvath, I F, Szanto, A, Tarr, T, Seror, R, Mariette, X, Mandl, T, Olsson, P, Li, X, Xu, B, Baldini, C, Bombardieri, S, Gottenberg, J E, Gandolfo, S, De Vita, S, Priori, R, Giardina, F, Hernandez-Molina, G, Sánchez-Guerrero, J, Kruize, A A, Hinrichs, A, Valim, V, Isenberg, D, Solans, R, Rischmueller, M, Downie-Doyle, S, Kwok, S-K, Park, S-H, Nordmark, G, Suzuki, Y, Kawano, M, Giacomelli, R, Devauchelle-Pensec, V, Saraux, A, Hofauer, B, Knopf, A, Bootsma, H, Vissink, A, Morel, J, Vollenveider, C, Atzeni, F, Retamozo, S, Moça Trevisano, V, Armagan, B, Kilic, L, Kalyoncu, U, Pasoto, S G, Kostov, B, Sisó-Almirall, A, Consani-Fernández, S, Carubbi, F, Callejas, J L, López-Dupla, M, Pérez-Alvarez, R, Akasbi, M, Guisado-Vasco, P, Sánchez, I, Hospital Universitario 12 de Octubre [Madrid], EULAR standing committee of People with Arthritis/Rheumatism in Europe (PARE), H. CIMA-Sanitas, Barcelona, CELLEX-IDIBAPS Department of Autoimmune Diseases, Barcelona, Instituto Mexicano del Seguro Social [Mexico City, Mexico] (IMSS), Universidad de Colima [Mexico], Hospital Clinic [Barcelona, Spain], İstanbul Üniversitesi, İstanbul, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary, MTA-Debreceni Egyetem, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin Bicêtre, Skåne University Hospital [Malmö, Suède], Stockholm University, Wuhan University [China], Pisa University Hospital, Nuclear Medicine Unit, Humanitas Gavazzeni, Bergamo, Italy, University Hospitals, Strasbourg, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán - National Institute of Medical Science and Nutrition Salvador Zubiran [Mexico], Federal University of Espírito Santo, University Hospital Vall d’Hebròn [Barcelona, Spain], Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut d'Investigaciones Biomèdiques August Pi i Sunye (IDIBAPS), Università degli studi di Palermo - University of Palermo, Hospitales Universitarios de Granada/Universidad de Granada, Hospital Universitario Quironsalud, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Rheumatology Unit, Department of Internal Medicine, University of Palermo, Palermo, Italy, and Michel, Geneviève
Subjects: Male, medicine.medical_specialty, Multivariate analysis, [SDV.IMM] Life Sciences [q-bio]/Immunology, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Comorbidity, Laboratory abnormality, comorbidities, outcomes, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Risk Factors, Internal medicine, medicine, Humans, In patient, Pharmacology (medical), 030212 general & internal medicine, Registries, Risk factor, Primary Sjögren Syndrome, AcademicSubjects/MED00360, ComputingMilieux_MISCELLANEOUS, 030203 arthritis & rheumatology, business.industry, SARS-CoV-2, COVID-19, Primary SS, SARS-Cov-2, Middle Aged, medicine.disease, 3. Good health, Hospitalization, Sjogren's Syndrome, [SDV.IMM]Life Sciences [q-bio]/Immunology, Original Article, Female, business
Abstract: Objective To analyse the prognosis and outcomes of SARS-CoV-2 infection in patients with primary SS. Methods We searched for patients with primary SS presenting with SARS-CoV-2 infection (defined following and according to the European Centre for Disease Prevention and Control guidelines) among those included in the Big Data Sjögren Registry, an international, multicentre registry of patients diagnosed according to the 2002/2016 classification criteria. Results A total of 51 patients were included in the study (46 women, mean age at diagnosis of infection of 60 years). According to the number of patients with primary SS evaluated in the Registry (n = 8211), the estimated frequency of SARS-CoV-2 infection was 0.62% (95% CI 0.44, 0.80). All but two presented with symptoms suggestive of COVID-19, including fever (82%), cough (57%), dyspnoea (39%), fatigue/myalgias (27%) and diarrhoea (24%), and the most frequent abnormalities included raised lactate dehydrogenase (LDH) (88%), CRP (81%) and D-dimer (82%) values, and lymphopenia (70%). Infection was managed at home in 26 (51%) cases and 25 (49%) required hospitalization (five required admission to ICU, four died). Compared with patients managed at home, those requiring hospitalization had higher odds of having lymphopenia as laboratory abnormality (adjusted OR 21.22, 95% CI 2.39, 524.09). Patients with comorbidities had an older age (adjusted OR 1.05, 95% CI 1.00, 1.11) and showed a risk for hospital admission six times higher than those without (adjusted OR 6.01, 95% CI 1.72, 23.51) in the multivariate analysis. Conclusion Baseline comorbidities were a key risk factor for a more complicated COVID-19 in patients with primary SS, with higher rates of hospitalization and poor outcomes in comparison with patients without comorbidities.
Published: 2020

21. Cobimetinib plus atezolizumab in BRAFV600 wild-type melanoma: primary results from the randomized phase III IMspire170 study

Author: Daniil Stroyakovskiy, Yu Guo, Isabelle Rooney, P. Francesco Ferrucci, Keith T. Flaherty, Zeynep Eroglu, Jacopo Pigozzo, S. Troutman, Jacek Mackiewicz, S. Mulla, Athina Voulgari, Piotr Rutkowski, Bethany Pitcher, Brigitte Dréno, Lev V. Demidov, J.M.G. Larkin, A. Arance, M. Castro, Helen Gogas, Yibing Yan, National and Kapodistrian University of Athens (NKUA), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Royal Marsden NHS Foundation Trust, N.N. Blokhin Russian Cancer Research Center, Moscow City Oncology Hospital No. 62 [Moscow, Russia] (MCOH), H. Lee Moffitt Cancer Center and Research Institute, European Institute of Oncology [Milan] (ESMO), Veneto Institute of Oncology IOV-IRCCS [Padua, Italy], Maria Sklodowska-Curie National Research Institute of Oncology [Krakow, Poland], Poznan University of Medical Sciences [Poland] (PUMS), Genentech, Inc. [San Francisco], Roche Products Ltd, F. Hoffmann-La Roche [Basel], Massachusetts General Hospital Cancer Center [Boston, MA, USA], Harvard Medical School [Boston] (HMS), Hospital Clinic [Barcelona, Spain], and Malbec, Odile
Subjects: 0301 basic medicine, atezolizumab, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Population, Pembrolizumab, Gastroenterology, BRAF wild-type, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Atezolizumab, Interquartile range, Internal medicine, medicine, melanoma, education, Adverse effect, cobimetinib, Cobimetinib, education.field_of_study, business.industry, Hazard ratio, Hematology, Rash, [SDV] Life Sciences [q-bio], 030104 developmental biology, Oncology, chemistry, 030220 oncology & carcinogenesis, pembrolizumab, medicine.symptom, business
Abstract: International audience; Background: Emerging data suggest that the combination of MEK inhibitors and immunotherapeutic agents may result in improved efficacy in melanoma. We evaluated whether combining MEK inhibition and immune checkpoint inhibition was more efficacious than immune checkpoint inhibition alone in patients with previously untreated BRAF V600 wild-type advanced melanoma. Patients and methods: IMspire170 was an international, randomized, open-label, phase III study. Patients were randomized 1 : 1 to receive cobimetinib (60 mg, days 1-21) plus anti-programmed death-ligand 1 atezolizumab (840 mg every 2 weeks) in 28-day cycles or anti-programmed death-1 pembrolizumab (200 mg every 3 weeks) alone until loss of clinical benefit, unacceptable toxicity, or consent withdrawal. The primary outcome was progression-free survival (PFS), assessed by an independent review committee in the intention-to-treat population. Results: Between 11 December 2017, and 29 January 2019, 446 patients were randomized to receive cobimetinib plus atezolizumab (n ¼ 222) or pembrolizumab (n ¼ 224). Median follow-up was 7.1 months [interquartile range (IQR) 4.8-9.9] for cobimetinib plus atezolizumab and 7.2 months (IQR 4.9-10.1) for pembrolizumab. Median PFS was 5.5 months [95% confidence interval (CI) 3.8-7.2] with cobimetinib plus atezolizumab versus 5.7 months (95% CI 3.7-9.6) with pembrolizumab [stratified hazard ratio 1.15 (95% CI 0.88-1.50); P ¼ 0.30]. Hazard ratios for PFS were consistent across prespecified subgroups. In exploratory biomarker analyses, higher tumor mutational burden was associated with improved clinical outcomes in both treatment arms. The most common grade 3-5 adverse events (AEs) were increased blood creatine phosphokinase (10.0% with cobimetinib plus atezolizumab versus 0.9% with pembrolizumab), diarrhea (7.7% versus 1.9%), rash (6.8% versus 0.9%), hypertension (6.4% versus 3.7%), and dermatitis acneiform (5.0% versus 0). Serious AEs occurred in 44.1% of patients with cobimetinib plus atezolizumab and 20.8% with pembrolizumab. Conclusion: Cobimetinib plus atezolizumab did not improve PFS compared with pembrolizumab monotherapy in patients with BRAF V600 wild-type advanced melanoma.
Published: 2020

22. Dual therapy combining raltegravir with etravirine maintains a high level of viral suppression over 96 weeks in long-term experienced HIV-infected individuals over 45 years on a PI-based regimen: results from the Phase II ANRS 163 ETRAL study-authors' response

Author: Christine Katlama, Lambert Assoumou, Marc-Antoine Valantin, Cathia Soulié, Esteban Martinez, Lydie Béniguel, Olivier Bouchaud, François Raffi, Jean-Michel Molina, Soraya Fellahi, Gilles Peytavin, Anne-Geneviève Marcelin, Sami Kolta, Jacqueline Capeau, Severine Gibowski, Fanny Cardon, Jacques Reynes, Dominique Costagliola, Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de virologie [CHU Pitié-Salpêtrière], Hospital Clinic [Barcelona, Spain], Universitat de Barcelona (UB), Service de maladies infectieuses et tropicales [CHU Avicenne], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris 13 (UP13), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Sorbonne Paris Cité (USPC), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Pathologies biliaires, fibrose et cancer du foie [CHU Saint-Antoine], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], ANRS France Recherche Nord & sud Sida-hiv hépatites, Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), and Université Montpellier 1 (UM1)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: Microbiology (medical), MESH: Raltegravir Potassium, Anti-HIV Agents, HIV Infections, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Pyridazines, Raltegravir Potassium, Nitriles, Humans, Pharmacology (medical), 030212 general & internal medicine, MESH: Anti-HIV Agents, ComputingMilieux_MISCELLANEOUS, Pharmacology, 0303 health sciences, MESH: Humans, 030306 microbiology, MESH: HIV Infections, MESH: Nitriles, 3. Good health, Pyridazines, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Pyrimidines, MESH: Pyrimidines, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology
Abstract: International audience
Published: 2020

23. Presenting Features and Early Mortality from SARS-CoV-2 Infection in Cancer Patients during the Initial Stage of the COVID-19 Pandemic in Europe

Author: Rachel Sharkey, Roxana Reyes, Josep Tabernero, Joanne Evans, Daniela Ferrante, Joan Brunet, Andrea Patriarca, Mattia Bellan, Gianluca Gaidano, Isabel Garcia-Fructuoso, Anna Carbó, Christopher C T Sng, Alessandra Gennari, Mark Bower, Sarah Benafif, Alessia Dalla Pria, Lorenza Scotti, Elia Seguí, Riccardo Bruna, Francesca D'Avanzo, Aleix Prat, Claudia Andrea Cruz, Diego Ottaviani, Gianpiero Rizzo, Yien Ning Sophia Wong, Meritxell Mollà, Mario Pirisi, Pier Paolo Sainaghi, Thomas Newsom-Davis, Isabel Ruiz-Camps, Gian Carlo Avanzi, Myria Galazi, Javier Marco-Hernández, David J. Pinato, Federica Biello, Alvin J.X. Lee, Neha Chopra, Juan Aguilar-Company, Carme Carmona, Luigi Mario Castello, Wellcome Trust, Pinato, D, Lee, A, Biello, F, Segui, E, Aguilar-Company, J, Carbo, A, Bruna, R, Bower, M, Rizzo, G, Benafif, S, Carmona, C, Chopra, N, Cruz, C, D'Avanzo, F, Evans, J, Galazi, M, Garcia-Fructuoso, I, Pria, A, Newsom-Davis, T, Ottaviani, D, Patriarca, A, Reyes, R, Sharkey, R, Sng, C, Wong, Y, Ferrante, D, Scotti, L, Avanzi, G, Bellan, M, Castello, L, Marco-Hernandez, J, Molla, M, Pirisi, M, Ruiz-Camps, I, Sainaghi, P, Gaidano, G, Brunet, J, Tabernero, J, Prat, A, Gennari, A, Institut Català de la Salut, [Pinato DJ] Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, London, UK. [Lee AJX] Department of Oncology, University College London Hospitals, London, UK. [Biello F] Department of Translational Medicine, Division of Oncology, University of Piemonte Orientale and Maggiore della Carita’ Hospital, Novara, Italy. [Seguí E] Department of Medical Oncology, Hospital Clinic, Barcelona, Spain. [Aguilar-Company J] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Carbó A] Department of Medical Oncology, Catalan Institute of Oncology, University Hospital Josep Trueta, Girona, Spain. [Ruiz-Camps I] Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Tabernero J] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, Coronaviru, coronavirus, Disease, Malignancy, outcomes, lcsh:RC254-282, survival, Article, neoplasias [ENFERMEDADES], 03 medical and health sciences, Otros calificadores::Otros calificadores::/complicaciones [Otros calificadores], 0302 clinical medicine, Internal medicine, Intensive care, Other subheadings::Other subheadings::Other subheadings::/mortality [Other subheadings], Pandemic, Càncer - Mortalitat, medicine, virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES], cancer, 1112 Oncology and Carcinogenesis, Stage (cooking), COVID-19 (Malaltia) - Complicacions, Outcome, Otros calificadores::Otros calificadores::Otros calificadores::/mortalidad [Otros calificadores], business.industry, SARS-CoV-2, Outbreak, Cancer, COVID-19, Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES], medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, mortality, Neoplasms [DISEASES], 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, business, Complication, Other subheadings::Other subheadings::/complications [Other subheadings]
Abstract: We describe the outcomes in cancer patients during the initial outbreak of the COVID-19 in Europe from the retrospective, multi-center observational OnCovid study. We identified 204 cancer patients from eight centers in the United Kingdom, Italy, and Spain aged &gt, 18 (mean = 69) and diagnosed with COVID-19 between February 26th and April 1st, 2020. A total of 127 (62%) were male, 184 (91%) had a diagnosis of solid malignancy, and 103 (51%) had non-metastatic disease. A total of 161 (79%) had &gt, 1 co-morbidity. A total of 141 (69%) patients had &gt, 1 COVID-19 complication. A total of 36 (19%) were escalated to high-dependency or intensive care. A total of 59 (29%) died, 53 (26%) were discharged, and 92 (45%) were in-hospital survivors. Mortality was higher in patients aged &gt, 65 (36% versus 16%), in those with &gt, 2 co-morbidities (40% versus 18%) and developing &gt, 1 complication from COVID-19 (38% versus 4%, p = 0.004). Multi-variable analyses confirmed age &gt, 65 and &gt, 2 co-morbidities to predict for patient mortality independent of tumor stage, active malignancy, or anticancer therapy. During the early outbreak of SARS-CoV-2 infection in Europe co-morbid burden and advancing age predicted for adverse disease course in cancer patients. The ongoing OnCovid study will allow us to compare risks and outcomes in cancer patients between the initial and later stages of the COVID-19 pandemic.
Published: 2020
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24. Prenatal exposure to a wide range of environmental chemicals and child behaviour between 3 and 7 years of age - An exposome-based approach in 5 European cohorts

Author: Jedynak, Paulina, MAITRE, Léa, Guxens, Mónica, Gützkow, Kristine, Julvez, Jordi, López-Vicente, Mónica, Sunyer, Jordi, Casas, Maribel, Chatzi, Leda, Gražulevičienė, Regina, Kampouri, Mariza, McEachan, Rosie, Mon-Williams, Mark, Tamayo, Ibon, Thomsen, Cathrine, Urquiza, José, Vafeiadi, Marina, Wright, John, Basagaña, Xavier, Vrijheid, Martine, Philippat, Claire, Inserm, CNRS, University Grenoble Alpes, Institute of Advanced Biosciences, Joint Research Center (U1209), Barcelona Institute for Global Health [Barcelona, Spain] (ISGlobal), University of Barcelona-Hospital Clinic [Barcelona, Spain], CIBER Epidemiologia y Salud Pùblica [Madrid, Spain] (CIBERESP), Instituto de Salud Carlos III [Madrid] (ISC), Universitat Pompeu Fabra [Barcelona] (UPF), Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Department of Child and Adolescent Psychiatry/Psychology, Erasmus Medical Centre–Sophia Children's Hospital, Rotterdam, the Netherlands, Norwegian Institute of Public Health [Oslo, Norway] (NIPH), Institut d'Investigació Sanitària Pere Virgili (IISPV), Hospital Universitari Sant Joan de Reus, Reus, Spain, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA, Department of Social Medicine, University of Crete, Heraklion, Greece, Department of Genetics and Cell Biology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands, Department of Environmental Sciences, Vytautas Magnus University, Kaunas, Lithuania, and Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK
Subjects: Child behaviour, Strengths and Difficulties Questionnaire, Child Behavior, Environmental Exposure, Internal exposome, Article, Cohort Studies, Exposome, Pregnancy, Prenatal Exposure Delayed Effects, Prenatal exposure, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Environmental Pollutants, Female, Child, ComputingMilieux_MISCELLANEOUS, Birth cohort
Abstract: Background Studies looking at associations between environmental chemicals and child behaviour usually consider only one exposure or family of exposures. Objective This study explores associations between prenatal exposure to a wide range of environmental chemicals and child behaviour. Methods We studied 708 mother-child pairs from five European cohorts recruited in 2003–2009. We assessed 47 exposure biomarkers from eight chemical exposure families in maternal blood or urine collected during pregnancy. We used the Strengths and Difficulties Questionnaire (SDQ) to evaluate child behaviour between three and seven years of age. We assessed associations of SDQ scores with exposures using an adjusted least absolute shrinkage and selection operator (LASSO) considering all exposures simultaneously and an adjusted exposome-wide association study (ExWAS) considering each exposure independently. Results LASSO selected only copper (Cu) as associated with externalizing behaviour. In the ExWAS, bisphenol A [BPA, incidence rate ratio (IRR): 1.06, 95% confidence interval (95%CI): 1.01;1.12] and mono-n-butyl phthalate (MnBP, IRR: 1.06, 95%CI: 1.00;1.13) were associated with greater risk of externalizing behaviour problems. Cu (IRR: 0.90, 95%CI: 0.82;0.98), perfluoroundecanoate (PFUnDA, IRR: 0.92, 95%CI: 0.84;0.99) and organochlorine compounds (OCs) were associated with lower risk of externalizing behaviour problems, however the associations with OCs were mainly seen among women with insufficient weight gain during pregnancy. Internalizing score worsen in association with exposure to diethyl thiophosphate (DETP, IRR: 1.11, 95%CI: 1.00;1.24) but the effect was driven by the smallest cohort. Internalizing score improved with increased concentration of perfluorooctane sulfonate (PFOS, IRR: 0.92, 95%CI: 0.85;1.00), however the association was driven by the two smallest cohorts with the lowest PFOS concentrations. Discussion This study added evidence on deleterious effects of prenatal exposure to BPA and MnBP on child behaviour. Other associations should be interpreted cautiously since they were not consistent with previous studies or they have not been studied extensively., Graphical abstract Unlabelled Image, Highlights • We studied simultaneous effect of prenatal exposure to several compounds on child behaviour. • 47 exposure biomarkers from 8 chemical exposure families were studied in 5 European cohorts. • Bisphenol A and mono-n-butyl phthalate were associated with increased behavioural problems in children. • Copper was associated with decreased behavioural problems.
Published: 2020

25. Long-Term Peridialytic Blood Pressure Patterns in Patients Treated by Hemodialysis and Hemodiafiltration

Author: Paul A. Rootjes, Camiel L.M. de Roij van Zuijdewijn, Muriel P.C. Grooteman, Michiel L. Bots, Bernard Canaud, Peter J. Blankestijn, Frans J. van Ittersum, Francisco Maduell, Marion Morena, Sanne A.E. Peters, Andrew Davenport, Robin W.M. Vernooij, Menso J. Nubé, Ferran Torres, Ercan Ok, Gulay Asci, Francesco Locatelli, Department of Nephrology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, VU University, Amsterdam, the Netherlands., Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Department of Nephrology, VU University Medical Center, Amsterdam, The Netherlands., Department of Nephrology, Hospital Clinic, Barcelona, Spain., Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), The George Institute for Global Health, University of Oxford, Oxford, UK, University College of London [London] (UCL), Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands, Department of Nephrology & Hypertension, University Medical Center Utrecht, Utrecht, the Netherlands, Nephrology, ACS - Diabetes & metabolism, ACS - Atherosclerosis & ischemic syndromes, MORNET, Dominique, and Academic Medical Center
Subjects: medicine.medical_specialty, Mean arterial pressure, medicine.medical_treatment, peridialytic, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Hemodynamics, 030204 cardiovascular system & hematology, lcsh:RC870-923, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Clinical Research, Internal medicine, medicine, hemodiafiltration, hemodialysis, business.industry, blood pressure, Retrospective cohort study, individual participant data, lcsh:Diseases of the genitourinary system. Urology, 3. Good health, Pulse pressure, [SDV] Life Sciences [q-bio], Blood pressure, Quartile, Nephrology, Cardiology, Hemodialysis, business
Abstract: Introduction Online postdilution hemodiafiltration (HDF) is associated with a lower all-cause and cardiovascular mortality than hemodialysis (HD). This may depend on a superior peridialytic (pre- and postdialysis, and the difference between these 2 parameters) hemodynamic profile. Methods In this retrospective cohort analysis of individual participant data (IPD) from 3 randomized controlled trials (RCTs) (n = 2011), the effect of HDF and HD on 2-year peridialytic blood pressure (BP) patterns was assessed. Long-term peridialytic systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and pulse pressure (PP), as well as the deltas (post- minus predialytic) were assessed in the total group of patients. Thereafter, these variables were compared between patients on HD and HDF, and in the latter group between quartiles of convection volume. Results Mean pre- and postdialysis SBP, DBP, and MAP declined significantly during follow-up (predialytic: SBP −2.16 mm Hg, DBP −2.88 mm Hg, MAP −2.64 mm Hg), PP increased (predialytic 0.96 mm Hg). Peridialytic deltas remained unaltered. Differences between the 2 modalities, or between quartiles of convection volume were not observed. BP changes were independent of various baseline characteristics, including the decline in body weight over time. Conclusion We speculate that the combination of a decreasing SBP and an increasing PP may be the clinical sequelae of a worsening cardiovascular system. Because especially HDF with a high convection volume has been associated with a beneficial effect on survival, our study does not support the view that superior peridialytic BP control contributes to this effect., Graphical abstract
Published: 2020

26. ISSAID/EMQN Best Practice Guidelines for the Genetic Diagnosis of Monogenic Autoinflammatory Diseases in the Next-Generation Sequencing Era

Author: Osamu Ohara, Guilaine Boursier, Dorota Rowczenio, Christian Oberkanins, Hiroaki Ida, Marco Gattorno, Nicola Wolstenholme, Laura Obici, Ivona Aksentijevich, Yael Shinar, Anna Mensa-Vilaro, Ryuta Nishikomori, Isabella Ceccherini, Hasmik Hayrapetyan, Nobuo Kanazawa, Helen J. Lachmann, Seza Ozen, Marielle E. van Gijn, Tamara Sarkisian, Evelien Zonneveld-Huijssoon, Isabelle Touitou, Katie Sheils, Juan I. Aróstegui, Eldad Ben-Chetrit, Chaim Sheba Medical Center, IRCCS Istituto Giannina Gaslini [Genoa, Italy], UCL Medical School, National Human Genome Research Institute (NHGRI), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Hadassah Hebrew University Medical Center [Jerusalem], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Kurume University School of Medicine, Kurume University, Wakayama Medical University, Hospital Clinic [Barcelona, Spain], ViennaLab Diagnostics GmbH, Fondazione IRCCS Policlinico San Matteo [Pavia], Università di Pavia, Kazusa DNA Research Institute (KDRI), Hacettepe University = Hacettepe Üniversitesi, St Mary's Hospital [London], University of Groningen [Groningen], Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: 0301 basic medicine, Adenosine Deaminase, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Next-Generation Sequencing (NGS), VARIANT, Nod2 Signaling Adaptor Protein, Familial Mediterranean fever, Disease, Bioinformatics, 0302 clinical medicine, Prenatal Diagnosis, Genotype, guidelines, Sanger sequencing, medicine.diagnostic_test, High-Throughput Nucleotide Sequencing, MEFV, 3. Good health, AMYLOIDOSIS, Practice Guidelines as Topic, symbols, Intercellular Signaling Peptides and Proteins, FAMILIAL MEDITERRANEAN FEVER, medicine.medical_specialty, SOMATIC MOSAICISM, Prenatal diagnosis, HAPLOINSUFFICIENCY, CARD15 MUTATIONS, PATIENT, 03 medical and health sciences, symbols.namesake, genetic diagnosis, Molecular genetics, medicine, Humans, Genetic Testing, Tumor Necrosis Factor alpha-Induced Protein 3, Genetic testing, Adaptor Proteins, Signal Transducing, 030203 arthritis & rheumatology, business.industry, DELETION, Biochemistry (medical), Hereditary Autoinflammatory Diseases, medicine.disease, autoinflammatory diseases, variant analysis, Cytoskeletal Proteins, 030104 developmental biology, business
Abstract: Background Monogenic autoinflammatory diseases are caused by pathogenic variants in genes that regulate innate immune responses, and are characterized by sterile systemic inflammatory episodes. Since symptoms can overlap within this rapidly expanding disease category, accurate genetic diagnosis is of the utmost importance to initiate early inflammation-targeted treatment and prevent clinically significant or life-threatening complications. Initial recommendations for the genetic diagnosis of autoinflammatory diseases were limited to a gene-by-gene diagnosis strategy based on the Sanger method, and restricted to the 4 prototypic recurrent fevers (MEFV, MVK, TNFRSF1A, and NLRP3 genes). The development of best practices guidelines integrating critical recent discoveries has become essential. Methods The preparatory steps included 2 online surveys and pathogenicity annotation of newly recommended genes. The current guidelines were drafted by European Molecular Genetics Quality Network members, then discussed by a panel of experts of the International Society for Systemic Autoinflammatory Diseases during a consensus meeting. Results In these guidelines, we combine the diagnostic strength of next-generation sequencing and recommendations to 4 more recently identified genes (ADA2, NOD2, PSTPIP1, and TNFAIP3), nonclassical pathogenic genetic alterations, and atypical phenotypes. We present a referral-based decision tree for test scope and method (Sanger versus next-generation sequencing) and recommend on complementary explorations for mosaicism, copy-number variants, and gene dose. A genotype table based on the 5-category variant pathogenicity classification provides the clinical significance of prototypic genotypes per gene and disease. Conclusions These guidelines will orient and assist geneticists and health practitioners in providing up-to-date and appropriate diagnosis to their patients.
Published: 2020

27. The STARMEN trial indicates that alternating treatment with corticosteroids and cyclophosphamide is superior to sequential treatment with tacrolimus and rituximab in primary membranous nephropathy

Author: Gema Fernández-Juárez, Jorge Rojas-Rivera, Anne-Els van de Logt, Joana Justino, Angel Sevillano, Fernando Caravaca-Fontán, Ana Ávila, Cristina Rabasco, Virginia Cabello, Alfonso Varela, Montserrat Díez, Guillermo Martín-Reyes, Marian Goicoechea Diezhandino, Luis F. Quintana, Irene Agraz, Juan Ramón Gómez-Martino, Mercedes Cao, Antolina Rodríguez-Moreno, Begoña Rivas, Cristina Galeano, Jose Bonet, Ana Romera, Amir Shabaka, Emmanuelle Plaisier, Mario Espinosa, Jesus Egido, Alfonso Segarra, Gérard Lambeau, Pierre Ronco, Jack Wetzels, Manuel Praga, Fernando Caravaca-Fontan, Hernando Trujillo, Eduardo Gutiérrez, Gema Fernandez Juarez, Alberto Ortiz, Marian Goicoechea, Úrsula Verdalles, Alfons Segarra, Lara Perea, Ildefonso Valera, Mónica Martín, Miguel Angel Pérez Valdivia, Miquel Blasco, Andrés López Muñiz, Ana Avila, Tamara Malek, Montserrat Diaz, Iara DaSilva, Jordi Bonet, Maruja Navarro, Ana Huerta, Ezequiel Rodríguez-Paternina, Ana Vigil, Roberto Alcázar, Vicente Paraíso, Vicente Barrio, Julia Hofstra, Institut Català de la Salut, [Fernández-Juárez G] Nephrology Division, Hospital Universitario Fundación Alcorcón, Madrid, Spain. [Rojas-Rivera J] Nephrology Division, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain. [Logt AV] Nephrology Division, Radboud University Medical Center, Nijmegen, The Netherlands. [Justino J] Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), Université Côte d’Azur, Centre National de la Recherche Scientifique (CNRS), Valbonne Sophia Antipolis, France. [Sevillano A, Caravaca-Fontán F] Nephrology Division, Instituto de Investigación Hospital Universitario 12 Octubre, Madrid, Spain. [Agraz I] Divisió de Nefrologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, Nephrology Division, Hospital Universitario Fundación Alcorcón, Madrid, Spain, Nephrology Division, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain, Radboud Institute for Health Sciences, Radboud University Medical Center [Nijmegen], Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Hospital Universitario 12 de Octubre [Madrid], Dr Peset University Hospital, Hospital Reina Sofia, Cordoba, Hospital Universitario Virgen del Rocío [Sevilla], Hospital of Virgen de la Victoria de Malaga, Institut Investigacions Biomèdiques (IBB) Sant Pau [Barcelona, Spain], Hospital Regional Universitario de Málaga = Regional University Hospital of Malaga [Spain], Hospital General Universitario 'Gregorio Marañón' [Madrid], Department of Nephrology, Hospital Clinic, Barcelona, Spain., Vall d'Hebron University Hospital [Barcelona], San Pedro de Alcantara Hospital [Cáceres, Espagne], Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), Universidade da Coruña (UDC), Spain, Hospital Clinico San Carlos, Hospital Clínico San Carlos, Hospital Universitario La Paz [Madrid, Espagne], Hospital Universitario Ramón y Cajal [Madrid], Universidad de Alcalá - University of Alcalá (UAH), Germans Trias i Pujol Hospital, Universitat Autònoma de Barcelona (UAB), Hospital General Universitario de Ciudad Real [Ciudad Real, Spain], Maladies rénales fréquentes et rares : des mécanismes moléculaires à la médecine personnalisée (CoRaKID), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Radboud Institute for Health Sciences [Nijmegen, the Netherlands], Hospital Universitario Fundación Alcorcón, Hospital Universitario Fundación Jiménez Díaz [Madrid, Spain], Barcelona Centre for International Health Research, Hospital Clinic (CRESIB), Universitat de Barcelona (UB), Hospital Universitario, A Coruña, Fundació Puigvert [Barcelona, Spain], Germans Trias i Pujol University Hospital [Badalona, Barcelona, Spain] (GTPUH), Hospital Universitario Puerta de Hierro-Majadahonda [Madrid, Spain], Getafe University Hospital, Madrid, Severo Ochoa Hospital, Hospital Universitario Infanta Leonor [Madrid], Del Henares Hospital, Hospital Universitario Infanta Sofía, Radboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, The Netherlan ds, Lambeau, Gerard, Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Hospital Regional Universitario de Málaga [Spain], Barcelona Autonomous University, Common and Rare Kidney Diseases = Maladies Rénales Fréquentes et Rares: des Mécanismes Moléculaires à la Médecine Personnalisée (CORAKID), and Germans Trias i Pujol University Hospital
Subjects: 0301 basic medicine, medicine.medical_specialty, Cyclophosphamide, medicine.drug_class, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Other subheadings::Other subheadings::/drug therapy [Other subheadings], Gastroenterology, Tacrolimus, Primary membranous nephropathy, law.invention, 03 medical and health sciences, 0302 clinical medicine, Membranous nephropathy, Randomized controlled trial, law, Internal medicine, medicine, Corticosteroids, ComputingMilieux_MISCELLANEOUS, business.industry, Male Urogenital Diseases::Urologic Diseases::Kidney Diseases [DISEASES], 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], 3. Good health, [SDV] Life Sciences [q-bio], Regimen, 030104 developmental biology, Nephrology, Avaluació de resultats (Assistència sanitària), Corticosteroid, Rituximab, Renal disorders Radboud Institute for Health Sciences [Radboudumc 11], business, Nephrotic syndrome, enfermedades urogenitales masculinas::enfermedades urológicas::enfermedades renales [ENFERMEDADES], Ronyons - Malalties - Tractament, medicine.drug
Abstract: Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER); Red de Investigación Renal (RedInRen); European Renal Association-European Dialysis and Transplant Association (ERA-EDTA); Fundación Renal Iñigo Álvarez de Toledo (FRIAT); Fundación para la Investigación Biomédica Hospital 12 de Octubre (i+12); Centre National de la Recherche Scientifique; Fondation Maladies Rares (LAM-RD_20170304); National Research Agency (ANR, grants MNaims ANR-17-CE17-0012-01); "Investments for the Future" Laboratory of Excellence SIGNALIFE, a network for innovation on signal transduction pathways in life sciences (ANR-11-LABX-0028-01); Initiative of Excellence (IDEX; UCAJedi ANR-15-IDEX-01); Fondation pour la Recherche Médicale (FRM, ING20140129210, DEQ20180339193, FDT201805005509). A cyclical corticosteroid-cyclophosphamide regimen is recommended for patients with primary membranous nephropathy at high risk of progression. We hypothesized that sequential therapy with tacrolimus and rituximab is superior to cyclical alternating treatment with corticosteroids and cyclophosphamide in inducing persistent remission in these patients. This was tested in a randomized, open-label controlled trial of 86 patients with primary membranous nephropathy and persistent nephrotic syndrome after six-months observation and assigned 43 each to receive six-month cyclical treatment with corticosteroid and cyclophosphamide or sequential treatment with tacrolimus (full-dose for six months and tapering for another three months) and rituximab (one gram at month six). The primary outcome was complete or partial remission of nephrotic syndrome at 24 months. This composite outcome occurred in 36 patients (83.7%) in the corticosteroid-cyclophosphamide group and in 25 patients (58.1%) in the tacrolimus-rituximab group (relative risk 1.44; 95% confidence interval 1.08 to 1.92). Complete remission at 24 months occurred in 26 patients (60%) in the corticosteroid-cyclophosphamide group and in 11 patients (26%) in the tacrolimus-rituximab group (2.36; 1.34 to 4.16). Anti-PLA2R titers showed a significant decrease in both groups but the proportion of anti-PLA2R-positive patients who achieved immunological response (depletion of anti-PLA2R antibodies) was significantly higher at three and six months in the corticosteroid-cyclophosphamide group (77% and 92%, respectively), as compared to the tacrolimus-rituximab group (45% and 70%, respectively). Relapses occurred in one patient in the corticosteroid-cyclophosphamide group, and three patients in the tacrolimus-rituximab group. Serious adverse events were similar in both groups. Thus, treatment with corticosteroid-cyclophosphamide induced remission in a significantly greater number of patients with primary membranous nephropathy than tacrolimus-rituximab.
Published: 2020

28. Trans-arterial chemoembolization as a loco-regional inducer of immunogenic cell death in hepatocellular carcinoma: implications for immunotherapy

Author: Petros Fessas, Alejandro Forner, David J. Pinato, Valentina Cacciato, Daniel M. Altmann, Beatriz Minguez, Takahiro Kaneko, Rosemary J. Boyton, Edoardo Casagrande, Robert D. Goldin, Ayse U. Akarca, Sam M. Murray, Federica Grillo, Edoardo G. Giannini, Alba Díaz, Claudio Avellini, Pierluigi Toniutto, Teresa Marafioti, Francesco Mauri, Vincenzo Mazzaferro, Sherrie Bhoori, Institut Català de la Salut, [Pinato DJ] Department of Surgery & Cancer, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, UK. Division of Oncology, Department of Translational Medicine, Universita del Piemonte Orientale 'A. Avogadro', Novara, Italy. [Murray SM] Department of Infectious Diseases, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, UK. [Forner A] Liver Unit, Barcelona Clinic Liver Cancer (BCLC) Group, University of Barcelona, Hospital Clinic, Barcelona, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain. [Kaneko T] Tokyo Medical and Dental University, Bunkyo-ku, Japan. [Fessas P] Department of Surgery & Cancer, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, UK. [Toniutto P] Hepatology and Liver Transplantation Unit, Department of Medical Area (DAME), University of Udine, Udine, Italy. [Mínguez B] Unitat del Fetge, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, Vall d'Hebron Barcelona Hospital Campus, Wellcome Trust, Cancer Research UK, and Imperial College Healthcare NHS Trust- BRC Funding
Subjects: Male, Cancer Research, Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Adenocarcinoma::Carcinoma, Hepatocellular [DISEASES], Therapeutics::Hemostatic Techniques::Embolization, Therapeutic::Chemoembolization, Therapeutic [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Lymphocyte, medicine.medical_treatment, MULTICENTER, Immunogenic Cell Death, PHENOTYPE, Other subheadings::Other subheadings::/drug therapy [Other subheadings], THERAPY, Hemostàtics, Fetge - Càncer - Tractament, DOUBLE-BLIND, 0302 clinical medicine, ABLATION, Immunology and Allergy, Medicine, Cytotoxic T cell, immunotherapy, liver neoplasms, RC254-282, neoplasias::neoplasias por tipo histológico::neoplasias glandulares y epiteliales::carcinoma::adenocarcinoma::carcinoma hepatocelular [ENFERMEDADES], Clinical/Translational Cancer Immunotherapy, 0303 health sciences, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, FOXP3, Middle Aged, 3. Good health, medicine.anatomical_structure, Oncology, Mort cel·lular, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Molecular Medicine, Immunogenic cell death, Female, Life Sciences & Biomedicine, Adult, Carcinoma, Hepatocellular, terapéutica::técnicas hemostáticas::embolización terapéutica::quimioembolización terapéutica [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], TRANSARTERIAL CHEMOEMBOLIZATION, BEVACIZUMAB, Immunology, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], 03 medical and health sciences, Humans, Chemoembolization, Therapeutic, COMBINATION, Aged, 030304 developmental biology, Pharmacology, Tumor microenvironment, Science & Technology, Gastroenterology & Hepatology, business.industry, Immunotherapy, medicine.disease, PHASE-III, SORAFENIB, Cancer research, business, CD8
Abstract: Immunotherapy; Liver neoplasms Inmunoterapia; Neoplasias hepáticas Immunoteràpia; Neoplàsies hepàtiques Background Modulation of adaptive immunity may underscore the efficacy of trans-arterial chemoembolization (TACE). We evaluated the influence of TACE on T-cell function by phenotypic lymphocyte characterization in samples of patients undergoing surgery with (T+) or without (T-) prior-TACE treatment. Methods We profiled intratumoral (IT), peritumoral (PT) and non-tumoral (NT) background tissue to evaluate regulatory CD4+/FOXP3+ (T-reg) and immune-exhausted CD8+/PD-1+ T-cells across T+ (n=58) and T− (n=61). We performed targeted transcriptomics and T-cell receptor sequencing in a restricted subset of samples (n=24) evaluated in relationship with the expression of actionable drivers of anti-cancer immunity including PD-L1, indoleamine 2,3 dehydrogenase (IDO-1), cytotoxic T-lymphocyte associated protein 4 (CTLA-4), Lag-3, Tim-3 and CD163. Results We analyzed 119 patients resected (n=25, 21%) or transplanted (n=94, 79%) for Child-Pugh A (n=65, 55%) and Barcelona Clinic Liver Cancer stage A (n=92, 77%) hepatocellular carcinoma. T+ samples displayed lower IT CD4+/FOXP3+ (p=0.006), CD8+ (p=0.002) and CD8+/PD-1+ and NT CD8+/PD-1+ (p
Published: 2021

29. Identification of 22q11.2 deletion syndrome via newborn screening for severe combined immunodeficiency: two years’ experience in Catalonia (Spain)

Author: Neus Castells, Albert Plaja, Mónica Martínez-Gallo, Andrea Martín-Nalda, Anna M. Cueto-González, Pere Soler-Palacín, Ana Argudo-Ramírez, Eduardo F. Tizzano, Roger Colobran, Jacques G. Rivière, Jose Luis Marín-Soria, [Martin-Nalda A, Riviere J, Soler-Palacin P] Unitat de Malalties Infeccioses Pediàtriques i Immunodeficiències, Servei de Pediatria, Vall d'Hebron Hospital Universitari, Barcelona, Spain. [Cueto-González AM, Plaja A, Castells N] Servei de Genètica Clínica i Molecular, Vall d'Hebron Hospital Universitari, Barcelona, Spain. [Argudo-Ramírez A, Marin-Soria JL] Newborn screening laboratory, Section of Congenital Errors of Metabolism, Biochemistry and Molecular Genetics Department, Hospital Clinic, Barcelona, Spain. [Martinez-Gallo M] Divisió d’Immunologia, Vall d'Hebron Hospital Universitari, Barcelona, Spain. [Colobran R] Servei de Genètica Clínica i Molecular, Vall d'Hebron Hospital Universitari, Barcelona, Spain. Divisió d’Immunologia, Vall d'Hebron Hospital Universitari, Barcelona, Spain. [Tizzano EF] Servei de Genètica Clínica i Molecular, Vall d'Hebron Hospital Universitari, Barcelona, Spain. Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: 0301 basic medicine, Pediatrics, 22q11.2 deletion, Other subheadings::/methods [Other subheadings], Chromosomes, Human, Pair 22, Comorbidity, 030105 genetics & heredity, CHARGE syndrome, Otros calificadores::/métodos [Otros calificadores], Síndromes de deficiència immunitària en els infants - Catalunya, Gene duplication, Chromosome Duplication, Copy-number variation, Genetics (clinical), diagnóstico::técnicas y procedimientos diagnósticos::técnicas de laboratorio clínico::cribado neonatal [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Comparative Genomic Hybridization, Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Genetic Diseases, Inborn::Primary Immunodeficiency Diseases::Severe Combined Immunodeficiency [DISEASES], Cribatge genètic, Original Article, Female, medicine.medical_specialty, Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Congenital Abnormalities::Abnormalities, Multiple::22q11 Deletion Syndrome::Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Congenital Abnormalities::Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Congenital Abnormalities::Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Congenital Abnormalities::Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Congenital Abnormalities::Congenital, Hereditary, and Neonatal Diseases and Abnormalities::DiGeorge Syndrome [DISEASES], Catalonia, lcsh:QH426-470, DNA Copy Number Variations, Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Neonatal Screening [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], 03 medical and health sciences, Neonatal Screening, Cataluña, enfermedades y anomalías neonatales congénitas y hereditarias::enfermedades del recién nacido::inmunodeficiencia combinada grave [ENFERMEDADES], Genetics, medicine, DiGeorge Syndrome, Humans, Abnormalities, Multiple, Multiplex ligation-dependent probe amplification, Síndrome de DiGeorge - Catalunya, Molecular Biology, Newborn screening, Severe combined immunodeficiency, business.industry, newborn screening, Infant, Newborn, severe combined immunodeficiencye, Original Articles, medicine.disease, enfermedades y anomalías neonatales congénitas y hereditarias::anomalías congénitas::anomalías múltiples::síndrome de deleción 22q11::enfermedades y anomalías neonatales congénitas y hereditarias::anomalías congénitas::enfermedades y anomalías neonatales congénitas y hereditarias::anomalías congénitas::enfermedades y anomalías neonatales congénitas y hereditarias::anomalías congénitas::enfermedades y anomalías neonatales congénitas y hereditarias::anomalías congénitas::enfermedades y anomalías neonatales congénitas y hereditarias::síndrome de DiGeorge [ENFERMEDADES], lcsh:Genetics, 030104 developmental biology, Spain, Severe Combined Immunodeficiency, Trisomy, business, Comparative genomic hybridization
Abstract: Background The current scenario of newborn screening is changing as DNA studies are being included in the programs of several countries. Severe combined immunodeficiency (SCID) disorders can be detected using quantitative PCR assays to measure T‐cell receptor excision circles (TRECs), a byproduct of correct T‐cell development. However, in addition to SCID, other T‐cell‐deficient phenotypes such as 22q11.2 deletion syndrome 22q11.2 duplication syndrome, CHARGE syndrome, and trisomy 21 are detected. Methods We present our experience with the detection of 22q11.2 deletion syndrome and 22q11.2 duplication syndrome in a series of 103,903 newborns included in the newborn screening program of Catalonia (Spain). Results Thirty newborns tested were positive (low TREC levels) and five were found to have copy number variations at the 22q11 region (4 deletions and 1 duplication) when investigated with array comparative genomic hybridization technology and MLPA. Conclusion Newborn screening for SCID enables detection of several conditions, such as 22q syndromes, which should be managed by prompt, proactive approaches with adequate counseling for families by a multidisciplinary team., Newborn screening (NBS) using T‐cell receptor excision circle (TREC) assays to detect severe combined immunodeficiency (SCID) has been established in several geographic areas. In addition to SCID, other T‐cell deficient conditions, such as 22q11.2 deletion syndrome (DS), CHARGE syndrome, and trisomy 21, can also be detected through NBS. An early diagnosis of 22q11.2 DS is associated with a better clinical outcome, mainly because of the possibility of early protocolled care, including rehabilitation and adapted school programs, an appropriate vaccination schedule, and adequate genetic counseling.
Published: 2019

30. Maternal Satisfaction with Healthcare after Perinatal Loss in Monochorionic Twin Pregnancy

Author: Druguet, Mònica, Nuño Gómez, Laura, Rodó, Carlota, Arévalo, Silvia, Carreras Moratonas, Elena, Gómez-Benito, Juana, Universitat Autònoma de Barcelona, [Druguet M] Quantitative Psychology Unit, Faculty of Psychology, University of Barcelona, Barcelona, Spain. [Nuño L] Quantitative Psychology Unit, Faculty of Psychology, University of Barcelona, Barcelona, Spain. Clinical Institute of Neuroscience (ICN), Hospital Clinic, Barcelona, Spain. [Rodó C, Arévalo S, Carreras E] Medicina Maternal I Fetal, Servei d’ Obstetrícia, Hospital Universitari Vall d’Hebron, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. [Gómez-Benito J] Quantitative Psychology Unit, Faculty of Psychology, University of Barcelona, Barcelona, Spain. Group on Measurement Invariance and Analysis of Change (GEIMAC), Institute of Neurosciences, University of Barcelona, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Fetus - Mort, Embaràs, lcsh:Medicine, 0302 clinical medicine, Pregnancy, Assistència sanitària, Health care, grief, 030212 general & internal medicine, Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Infant, Newborn, Diseases::Anemia, Neonatal::Fetofetal Transfusion [DISEASES], Depression (differential diagnoses), monochorionic pregnancy, media_common, Female Urogenital Diseases and Pregnancy Complications::Pregnancy Complications::Perinatal Death [DISEASES], Fetal surgery, education.field_of_study, fetal surgery, Health Care Quality, Access, and Evaluation::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Patient Satisfaction [HEALTH CARE], 030219 obstetrics & reproductive medicine, Medical care, psychological difficulties, Monochorionic pregnancy, General Medicine, Psychological difficulties, Test (assessment), Perinatal loss, Maternal satisfaction, professional care, Anxiety, medicine.symptom, medicine.medical_specialty, Pacients - Satisfacció, media_common.quotation_subject, Population, Affect (psychology), Article, 03 medical and health sciences, medicine, enfermedades y anomalías neonatales congénitas y hereditarias::enfermedades del recién nacido::anemia neonatal::transfusión fetofetal [ENFERMEDADES], perinatal loss, education, Professional care, enfermedades de los genitales femeninos y complicaciones del embarazo::complicaciones del embarazo::muerte perinatal [ENFERMEDADES], business.industry, lcsh:R, Beck Depression Inventory, Family medicine, maternal satisfaction, Fetus - Nutrició, Grief, calidad, acceso y evaluación de la atención sanitaria::calidad, acceso y evaluación de la atención sanitaria::calidad de la atención sanitaria::mecanismos de evaluación de la atención sanitaria::satisfacción del paciente [ATENCIÓN DE SALUD], business
Abstract: Introduction: The analysis of patients&rsquo, satisfaction with healthcare is recognised as being useful in the evaluation of health outcomes and perceived quality of care. Little is known, however, about how the psychological status of women who experience perinatal complications may affect their perceived satisfaction with care. Methods: We assessed healthcare satisfaction in 52 women who had undergone intrauterine surgery during a complicated monochorionic twin pregnancy and examined the influence that fetal loss and sociodemographic, clinical, and psychological factors had on the degree of satisfaction. Data were gathered in an individual interview and through the administration of the Medical Patient Satisfaction Questionnaire, Beck Depression Inventory, and State&ndash, Trait Anxiety Inventory. Relationships between variables were analysed using a chi-square test, Spearman&rsquo, s rho, Student&rsquo, s t test, and the Mann&ndash, Whitney U test, in accordance with the metric nature of the variables and the assumptions fulfilled. Results: Age and level of education were not associated with the degree of healthcare satisfaction. Negative but non-significant correlations were observed between the level of satisfaction and symptoms of anxiety and depression. Satisfaction with healthcare was high in the sample as a whole, although it was significantly higher among women who had not experienced fetal loss. There were no differences in satisfaction with services involving direct contact with medical staff, whereas satisfaction with indirect services was lower among women who had experienced perinatal loss. Conclusions: Due to the unique characteristics of this population, specialised care teams of both professional healthcare and indirect services are needed. Although administrative aspects of healthcare are regarded as being of secondary importance, this may not be the case with more vulnerable populations.
Published: 2019

31. Association of occupational exposure to disinfectants with incidence of chronic obstructive pulmonary disease among US female nurses

Author: Nicole Le Moual, Jan-Paul Zock, Krislyn M. Boggs, Paul K. Henneberger, Catherine Quinot, Orianne Dumas, Frank E. Speizer, Raphaëlle Varraso, Carlos A. Camargo, Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique (VIMA), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Channing Division of Network Medicine [Boston, USA] (Department of Medicine), Harvard Medical School [Boston] (HMS)-Brigham and Women's Hospital [Boston], Department of Emergency Medicine, Massachusetts General Hospital [Boston], Barcelona Institute for Global Health [Barcelona, Spain] (ISGlobal), University of Barcelona-Hospital Clinic [Barcelona, Spain], CIBER de Epidemiología y Salud Pública (CIBERESP), National Institute for Occupational Safety and Health, and Faraldo, Beatrice
Subjects: medicine.medical_specialty, Sodium Hypochlorite, [SDV]Life Sciences [q-bio], Nurses, Pulmonary Disease, Chronic Obstructive, 03 medical and health sciences, 0302 clinical medicine, Formaldehyde, Occupational Exposure, Internal medicine, medicine, Humans, Prospective Studies, 030212 general & internal medicine, Risk factor, Prospective cohort study, Occupational Health, Original Investigation, Asthma, 2. Zero hunger, COPD, business.industry, Research, Incidence, Incidence (epidemiology), Hazard ratio, Hydrogen Peroxide, General Medicine, Middle Aged, medicine.disease, Health Surveys, United States, respiratory tract diseases, 3. Good health, [SDV] Life Sciences [q-bio], Occupational Diseases, Quaternary Ammonium Compounds, Online Only, 030228 respiratory system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Glutaral, Female, Nurses' Health Study, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Body mass index, Disinfectants, Follow-Up Studies
Abstract: This cohort study evaluates data from the Nurses’ Health Study II to investigate the association of occupational exposure to disinfectants and other cleaning products with the incidence of chronic obstructive pulmonary disease (COPD) among female US registered nurses with no history of COPD at baseline., Key Points Question Is exposure to disinfectants and cleaning products associated with incidence of chronic obstructive pulmonary disease among health care workers? Findings In a cohort study of 73 262 US female nurses participating in the Nurses’ Health Study II who were followed up from 2009 to 2015, occupational exposure to cleaning products and disinfectants was significantly associated with a 25% to 38% increased risk of developing chronic obstructive pulmonary disease independent of asthma and smoking. Meaning This study’s findings suggest that regular use of chemical disinfectants among nurses may be a risk factor for developing chronic obstructive pulmonary disease., Importance Exposure to disinfectants in health care workers has been associated with respiratory health outcomes, including asthma. Despite the biological plausibility of an association between disinfectants (irritant chemicals) and risk of chronic obstructive pulmonary disease (COPD), available data are sparse. Objective To investigate the association between exposure to disinfectants and COPD incidence in a large cohort of US female nurses. Design, Setting, and Participants The Nurses’ Health Study II is a US prospective cohort study of 116 429 female registered nurses from 14 US states who were enrolled in 1989 and followed up through questionnaires every 2 years since. The present study included women who were still in a nursing job and had no history of COPD in 2009, and used data from the 2009 through 2015 questionnaires. Clean and complete data used for this analysis were available in July 2018, and analyses were conducted from September 2018 through August 2019. Exposures Occupational exposure to disinfectants, evaluated by questionnaire and a job-task-exposure matrix (JTEM). Main Outcomes and Measures Incident physician-diagnosed COPD evaluated by questionnaire. Results Among the 73 262 women included in the analyses, mean (SD) age at baseline was 54.7 (4.6) years and 70 311 (96.0%) were white, 1235 (1.7%) black, and 1716 (2.3%) other; and 1345 (1.8%) Hispanic, and 71 917 (98.2%) non-Hispanic. Based on 368 145 person-years of follow-up, 582 nurses reported incident physician-diagnosed COPD. Weekly use of disinfectants to clean surfaces only (16 786 [22.9%] of participants exposed) and to clean medical instruments (13 899 [19.0%] exposed) was associated with COPD incidence, with adjusted hazard ratios of 1.38 (95% CI, 1.13-1.68) for cleaning surfaces only and 1.31 (95% CI, 1.07-1.61) for cleaning medical instruments after adjustment for age, smoking (pack-years), race, ethnicity, and body mass index. High-level exposure, evaluated by the JTEM, to several specific disinfectants (ie, glutaraldehyde, bleach, hydrogen peroxide, alcohol, and quaternary ammonium compounds) was significantly associated with COPD incidence, with adjusted hazard ratios ranging from 1.25 (95% CI, 1.04-1.51) to 1.36 (95% CI, 1.13-1.64). Associations were not modified by smoking or asthma status (P for interaction > .15). Conclusions and Relevance These longitudinal results suggest that regular use of chemical disinfectants among nurses may be a risk factor for developing COPD. If future studies confirm these results, exposure-reduction strategies that are compatible with infection control in health care settings should be developed.
Published: 2019

32. Letter to the Editor: Patient-Reported Outcomes for Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis: Rationale for Expanded Use

Author: Martin Duracinsky, Jeffrey V. Lazarus, Fabienne Marcellin, Patrizia Carrieri, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Recherche Clinique ville-hôpital, Méthodologies et Société (REMES), Université Paris Diderot - Paris 7 (UPD7), service de Médecine Interne et d'Immunologie Clinique [AP-HP Hôpital Bicêtre], Université Paris-Sud - Paris 11 (UP11)-Hôpital Bicêtre, Assistance Publique - Hôpitaux de Paris (AP-HP), Centre d'essais cliniques en économie de la santé [Hôtel Dieu - APHP], Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Barcelona Institute for Global Health [Barcelona, Spain] (ISGlobal), University of Barcelona-Hospital Clinic [Barcelona, Spain], and Dupuis, Christine
Subjects: Nonalcoholic steatohepatitis, medicine.medical_specialty, Letter to the editor, Hepatology, [SDV.IMM] Life Sciences [q-bio]/Immunology, business.industry, medicine.disease, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Liver, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Non-alcoholic Fatty Liver Disease, Internal medicine, Nonalcoholic fatty liver disease, medicine, Humans, [SDV.IMM]Life Sciences [q-bio]/Immunology, 030211 gastroenterology & hepatology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 030212 general & internal medicine, Patient Reported Outcome Measures, business, ComputingMilieux_MISCELLANEOUS
Abstract: International audience; no abstract
Published: 2019

33. Autologous stem cell transplantation for primary mediastinal B-cell lymphoma: long-term outcome and role of post-transplant radiotherapy. A report of the European Society for Blood and Marrow Transplantation

Author: Avivi, Irit, Boumendil, Ariane, Finel, Hervé, Nagler, Arnon, de Sousa, Aïda Botelho, Santasusana, Josep Maria Ribera, Vandenberghe, Elizabeth, Afanasyev, Peter, Bordessoule, Dominique, Moraleda, José Maria, Garcia, Eulogio Conde, Pohlreich, David, Garcia, Gonzalo Gutiérrez, Thomson, Kirsty, Or, Reuven, Beelen, Dietrich, Zuffa, Eliana, Giebel, Sebastian, Berthou, Christian, Salles, Gilles, Melpignano, Angela, Montoto, Silvia, Dreger, Peter, Afanasyev, Boris, Tel Aviv Sourasky Medical Center [Te Aviv], Service de Réanimation Médicale [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Lymphoma Working Party, Paris (EBMT), Centre International des greffes [CHU Saint-Antoine] (EBMT), The Chaim Sheba Medical Center [Tel Hashomer, Israel], Hospital de St. António dos Capuchos, Jose Carreras Research Institute, Hospital Universitari Germans Trias i Pujol, Hospital Universitario Germans Trias I Pujol, St. Jame's Hospital, First Pavlov State Medical University of St. Petersburg [Russian Federation], CHU Limoges, Hospital Universitario Virgen de la Arrixaca, Hospital Universitario Marqués de Valdecilla [Santander], Charles University Hospital, Hospital Clinic [Barcelona, Spain], University College London Medical School, University College London (UCL), Hadassah Hebrew University Medical Center [Jerusalem], Dept. of Bone Marrow Transplantation, University Hospital, Essen, University Hospital Essen, Unita Operativa di Ematologia, Ravenna, Cancer Center Gliwice, CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), A. Perrino Hospital, St Bartholomew's and The London Hospital, Department of Medicine V, Universität Heidelberg [Heidelberg], SPb State I. Pavlov, and Medical University
Subjects: Oncology, Adult, Male, medicine.medical_specialty, Lymphoma, B-Cell, Transplantation Conditioning, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Medizin, Transplantation, Autologous, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Autologous stem-cell transplantation, Internal medicine, medicine, Humans, Young adult, Aged, Retrospective Studies, Transplantation, business.industry, Hematopoietic Stem Cell Transplantation, Retrospective cohort study, Hematology, Middle Aged, medicine.disease, 3. Good health, Lymphoma, Radiation therapy, Europe, Treatment Outcome, 030220 oncology & carcinogenesis, Rituximab, Female, Primary mediastinal B-cell lymphoma, business, 030215 immunology, medicine.drug
Abstract: International audience; The purpose of this retrospective registry study was to investigate the outcome of autoSCT for primary mediastinal B-cell lymphoma (PMBCL) in the rituximab era, including the effects of eventual post-transplant radiotherapy (RT) consolidation. Patients with PMBCL aged between 18 and 70 years who were treated with a first autoSCT between 2000 and 2012 and registered with the EBMT were eligible. Eighty-six patients with confirmed PMBCL and the full data set required for this analysis were evaluable. Sixteen patients underwent autoSCT in remission after first-line therapy (CR/PR1), 44 patients were transplanted with chemosensitive relapsed or primary refractory disease (CR/PR >1), and 24 patients were chemorefractory at the time of autoSCT. With a median follow-up of 5 years, 3-year estimates of relapse incidence, progression-free survival, and overall survival were 6%, 94%, and 100% for CR/PR1; 31%, 64%, and 85% for CR/PR >1; and 52%, 39%, and 41% for REF, respectively. Whilst there was no significant benefit of post-transplant RT in the CR/PR >1 group, RT could completely prevent disease recurrence post d100 in the refractory group. In conclusion, autoSCT with or without consolidating RT is associated with excellent outcome in chemoimmunotherapy-sensitive PMBCL, whereas its benefits seem to be limited in chemoimmunotherapy-refractory disease.
Published: 2018

34. Characterization and risk estimate of cancer in patients with primary Sjögren syndrome

Author: Brito-Zerón, Pilar, Kostov, Belchin, Fraile, Guadalupe, Caravia-Durán, Daniel, Maure, Brenda, Rascón, Francisco-Javier, Zamora, Mónica, Casanovas, Arnau, Lopez-Dupla, Miguel, Ripoll, Mar, Pinilla, Blanca, Fonseca, Eva, Akasbi, Miriam, de la Red, Gloria, Duarte-Millán, Miguel-Angel, Fanlo, Patricia, Guisado-Vasco, Pablo, Pérez-Alvarez, Roberto, Chamorro, Antonio J, Morcillo, César, Jiménez-Heredia, Iratxe, Sánchez-Berná, Isabel, López-Guillermo, Armando, Ramos-Casals, Manuel, SS Study Group GEAS-SEMI, The SS Study Group GEAS-SEMI, [Morcillo,C, Brito-Zerón,P] Autoimmune Diseases Unit, Department of Internal Medicine, Hospital CIMA-Sanitas, Barcelona, Spain. [Brito-Zerón, P: Sánchez-Berná,I, Ramos-Casals,M] Laboratory of Autoimmune Diseases Josep Font, IDIBAPS, Department of Autoimmune Diseases, ICMiD, Hospital Clínic, Barcelona, Spain. [Kostov,B] Transversal group for research in primary care, IDIBAPS, Consorci d’Atenció Primària de Salut Barcelona Esquerre (CAPSBE), Barcelona, Spain. [Fraile,G] Department of Internal Medicine, Hospital Ramón y Cajal, Madrid, Spain. [Caravia-Durán,D] Department of Internal Medicine, Hospital Universitario Central de Asturias, Oviedo, Spain. [Maure,B] Department of Internal Medicine, Complejo Hospitalario Universitario, Vigo, Spain. [Rascón,FJ] Department of Internal Medicine, Hospital Son Espases, Palma de Mallorca, Spain. [Zamora,M, and Sánchez-Berná,I] Department of Internal Medicine, Hospital Virgen de las Nieves, Granada, Spain. [Casanovas,A] Department of Internal Medicine, Hospital Parc Taulí, Sabadell, Spain. [ Lopez-Dupla,M] Department of Internal Medicine, Hospital Joan XXIII, Tarragona, Spain. [Ripoll,M] Department of Internal Medicine, Hospital Infanta Sofía, Madrid, Spain. [Pinilla,B] Department of Internal Medicine, Hospital Gregorio Marañón, Madrid, Spain. [Fonseca,E] Department of Internal Medicine, Hospital de Cabueñes, Gijón, Spain. [Akasbi,M] Department of Internal Medicine, Hospital Infanta Leonor, Madrid, Spain. [de la Red,G] Department of Internal Medicine, Hospital Esperit Sant, Santa Coloma de Gramenet, Spain. [Duarte-Millán,MA] Department of Internal Medicine, Hospital de Fuenlabrada, Fuenlabrada, Spain. [Fanlo,P] Department of Internal Medicine, Hospital Virgen del Camino, Pamplona, Spain. [Guisado-Vasco,P] Department of Internal Medicine, Complejo Hospitalario Ruber Juan Bravo, Madrid, Spain. [Pérez-Alvarez,R] Department of Internal Medicine, Hospital Alvaro Cunqueiro, Vigo, Spain. [Chamorro,AJ] Department of Internal Medicine, Hospital de Salamanca, Salamanca, Spain. [ Jiménez-Heredia,i] Department of Internal Medicine, Hospital de Sagunto, Valencia, Spain. [López-Guillermo,A] Department of Hematology, ICMHO, Hospital Clinic, Barcelona, Spain. [Ramos-Casals,M] Department of Medicine, University of Barcelona, Barcelona, Spain.
Subjects: Oncology, Male, Cancer Research, Pathology, Lymphoma, Databases, Factual, modelos de riesgos proporcionales, humanos, Diseases::Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Thyroid Neoplasms [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Cohort Studies, Enfermedad de hodgkin, 0302 clinical medicine, immune system diseases, hemic and lymphatic diseases, Neoplasms, Análisis de regresión, evaluación de riesgos, Gammopatía monoclonal de relevancia indeterminada, Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Plasma Cell::Multiple Myeloma [Medical Subject Headings], Sjogren syndrome, Stomach cancer, estudios de cohortes, Thyroid cancer, Neoplasias de la tiroides, Multiple myeloma, mediana edad, Síndrome de sjögren, Cancer, Labio, neoplasias, anciano, Hematology, Incidence, Pronóstico, Diseases::Neoplasms::Neoplasms by Histologic Type::Lymphoma::Hodgkin Disease [Medical Subject Headings], Diseases::Hemic and Lymphatic Diseases::Hematologic Diseases::Blood Protein Disorders::Hypergammaglobulinemia::Monoclonal Gammopathy of Undetermined Significance [Medical Subject Headings], lcsh:Diseases of the blood and blood-forming organs, adulto, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Prognosis, humanities, pronóstico, Sjogren's Syndrome, 030220 oncology & carcinogenesis, Hematologic Neoplasms, Linfoma de células b de la zona marginal, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Globulins::Serum Globulins::Immunoglobulins::Paraproteins::Cryoglobulins [Medical Subject Headings], Female, Estudios de seguimiento, Incidencia, Anatomy::Stomatognathic System::Mouth::Lip [Medical Subject Headings], Adult, medicine.medical_specialty, Neoplasias gástricas, Lymphoma, B-Cell, lcsh:RC254-282, Risk Assessment, incidencia, 03 medical and health sciences, Crioglobulinas, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Morbidity::Incidence [Medical Subject Headings], Internal medicine, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Follow-Up Studies [Medical Subject Headings], medicine, Diseases::Immune System Diseases::Autoimmune Diseases::Arthritis, Rheumatoid::Sjogren's Syndrome [Medical Subject Headings], Humans, linfoma, Molecular Biology, Aged, Proportional Hazards Models, 030203 arthritis & rheumatology, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Regression Analysis [Medical Subject Headings], Proportional hazards model, business.industry, lcsh:RC633-647.5, Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Stomach Neoplasms [Medical Subject Headings], Research, Mieloma múltiple, medicine.disease, neoplasias hematológicas, Diseases::Neoplasms::Neoplasms by Histologic Type::Lymphoma::Lymphoma, Non-Hodgkin::Lymphoma, B-Cell::Lymphoma, B-Cell, Marginal Zone [Medical Subject Headings], Sjögren syndrome, stomatognathic diseases, Risk Estimate, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis [Medical Subject Headings], business
Abstract: Background: The purpose of this study is to characterize the risk of cancer in a large cohort of patients with primary Sjogren syndrome (SjS). Methods: We had analyzed the development of cancer in 1300 consecutive patients fulfilling the 2002 SjS classification criteria. The baseline clinical and immunological characteristics and systemic activity (ESSDAI scores) were assessed at diagnosis as predictors of cancer using Cox proportional hazards regression analysis adjusted for age at diagnosis and gender. The sex-and age-specific standardized incidence ratios (SIR) of cancer were estimated from 2012 Spanish mortality data. Results: After a mean follow-up of 91 months, 127 (9.8%) patients developed 133 cancers. The most frequent type of cancer was B-cell lymphoma (including 27 MALT and 19 non-MALT B-cell lymphomas). Systemic activity at diagnosis of primary SjS correlated with the risk of hematological neoplasia and cryoglobulins with a high risk of either B-cell or non-B-cell lymphoma subtypes. Patients with cytopenias had a high risk of non-MALT B-cell and non-B-cell cancer, while those with low C3 levels had a high risk of MALT lymphomas and those with monoclonal gammopathy and low C4 levels had a high risk of non-MALT lymphomas. The estimated SIR for solid cancer was 1. 13 and 11.02 for hematological cancer. SIRs for specific cancers were 36.17 for multiple myeloma and immunoproliferative diseases, 19.41 for Hodgkin lymphoma, 6.04 for other non-Hodgkin lymphomas, 5.17 for thyroid cancer, 4.81 for cancers of the lip and oral cavity, and 2.53 for stomach cancer. Conclusions: One third of cancers developed by patients with primary SjS are B-cell lymphomas. The prognostic factors identified at SjS diagnosis differed according to the subtype of B-cell lymphoma developed. Primary SjS is also associated with the development of some non-hematological cancers (thyroid, oral cavity, and stomach)., This work is supported by the Grant Fondo de Investigaciones Sanitarias (MRC, INT15/00085) and by the CERCA Programme/Generalitat de Catalunya.
Published: 2017

35. First month prednisone dose predicts prednisone burden during the following 11 months: an observational study from the RELES cohort

Author: Ruiz-Irastorza, G., Garcia, M., Espinosa, G., Caminal, L., Mitjavila, F., Gonzalez-Leon, R., Sopena, B., Canora, J., Villalba, M. V., Rodriguez-Carballeira, M., Lopez-Dupla, J. M., Callejas, J. L., Castro, A., Tolosa, C., Sanchez-Garcia, M. E., Perez-Conesa, M., Navarrete-Navarrete, N., Rodriguez, A. P., Herranz, M. T., Pallares, L., RELES, Autoimmune Dis Study Grp GEAS, [Ruiz-Irastorza, G.] Univ Basque Country, Autoimmune Dis Res Unit, Dept Internal Med, BioCruces Hlth Res Inst,Hosp Univ Cruces, Baracaldo, Bizkaia, Spain, [Garcia, M.] Univ Basque Country, Autoimmune Dis Res Unit, Dept Internal Med, BioCruces Hlth Res Inst,Hosp Univ Cruces, Baracaldo, Bizkaia, Spain, [Espinosa, G.] Hosp Clin Barcelona, Dept Autoimmune Dis, Barcelona, Spain, [Caminal, L.] Hosp Univ Cent Asturias, Dept Internal Med, Oviedo, Asturias, Spain, [Mitjavila, F.] Hosp Univ Bellvitge, Dept Internal Med, Autoimmune Dis Unit, Barcelona, Spain, [Gonzalez-Leon, R.] Hosp Univ Virgen del Rocio, Dept Internal Med, Seville, Spain, [Sopena, B.] Complejo Hosp Univ Vigo, Dept Internal Med, Vigo, Spain, [Canora, J.] Hosp Univ Fuenlabrada, Dept Internal Med, Madrid, Spain, [Villalba, M. V.] Hosp Gen Univ Gregorio Maranon, Dept Internal Med, Madrid, Spain, [Rodriguez-Carballeira, M.] Hosp Univ Mutua Terrasa, Dept Internal Med, Barcelona, Spain, [Lopez-Dupla, J. M.] Hosp Univ Joan XXIII, Dept Internal Med, Tarragona, Spain, [Callejas, J. L.] Hosp Univ San Cecilio, Dept Internal Med, Granada, Spain, [Castro, A.] Hosp Univ St Joan de Reus, Dept Internal Med, Tarragona, Spain, [Tolosa, C.] Corporacio Sanitaria Parc Tauli, Dept Internal Med, Barcelona, Spain, [Sanchez-Garcia, M. E.] Hosp Univ Reina Sofia, Dept Internal Med, Autoimmune Dis Unit, Cordoba, Spain, [Perez-Conesa, M.] Hosp Univ Miguel Servet, Dept Internal Med, Zaragoza, Spain, [Navarrete-Navarrete, N.] Hosp Univ Virgen de las Nieves, Dept Internal Med, Granada, Spain, [Rodriguez, A. P.] Complejo Hosp Univ Ourense, Dept Internal Med, Orense, Spain, [Herranz, M. T.] Hosp JM Morales Meseguer, Dept Internal Med, Murcia, Spain, [Pallares, L.] Hosp Univ Son Espases, Dept Internal Med, Islas Baleares, Spain, Spanish Society of Internal Medicine, RELES, Autoimmune Diseases Study Group (GEAS), [Ruiz-Irastorza,G, Garcia,M] Autoimmune Diseases Research Unit, Department of Internal Medicine, BioCruces Health Research Institute, Hospital Universitario Cruces, University of the Basque Country, Barakaldo, Bizkaia, Spain. [Espinosa,G] Department of Autoimmune Diseases, Hospital Clinic, Barcelona, Spain. [Caminal,L] Department of Internal Medicine, Hospital Universitario Central de Asturias, Oviedo, Asturias , Spain. [Mitjavila,F] Autoimmune Diseases Unit, Department of Internal Medicine, Hospital Universitario de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain. [González-León,R] Department of Internal Medicine , Hospital Universitario Virgen del Rocío, Sevilla, Spain. [Sopeña,B] Department of Internal Medicine, Complejo Hospitalario Universitario de Vigo, Pontevedra, Vigo , Spain. [Canora,J] Department of Internal Medicine, Hospital Universitario Fuenlabrada, Fuenlabrada, Madrid , Spain. [Villalba,MV] Department of Internal Medicine, Hospital General Universitario Gregorio Marañón, Madrid, Spain. [Rodríguez-Carballeira,M] Department of Internal Medicine, Hospital Universitario Mutua de Terrasa, Barcelona, Spain. [López-Dupla,JM] Department of Internal Medicine, Hospital Universitario Joan XXIII, Tarragona, Spain. [Callejas,JL] Department of Internal Medicine, Hospital Universitario San Cecilio, Granada, Spain. [Castro,A] Department of Internal Medicine, Hospital Universitario Sant Joan de Reus, Reus, Tarragona , Spain. [Tolosa,C] Department of Internal Medicine, Corporació Sanitària Parc Taulí, Sabadell, Barcelona, Spain. [Sánchez-García,ME] Department of Internal Medicine, Autoimmune Diseases Unit, Hospital Universitario Reina Sofía , Córdoba, Spain. [Pérez-Conesa,M] Department of Internal Medicine, Hospital Universitario Miguel Servet, Zaragoza, Spain. [Navarrete-Navarrete,N] Department of Internal Medicine , Hospital Universitario Virgen de las Nieves, Granada, Spain. [Rodríguez,AP] Department of Internal Medicine, Complejo Hospitalario Universitario de Ourense, Ourense, Spain. [Herranz,MT] Department of Internal Medicine, Hospital J.M. Morales Meseguer, Murcia, Spain. [Pallarés,L] Department of Internal Medicine, Hospital Universitario Son Espases, Palma de Mallorca, Islas Baleares, Spain., and This study was supported by the Spanish Society of Internal Medicine.
Subjects: 0301 basic medicine, Lupus nephritis, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, immune system diseases, Prednisone, Nefritis lúpica, Phenomena and Processes::Circulatory and Respiratory Physiological Phenomena::Cardiovascular Physiological Phenomena::Hemodynamics::Pulse [Medical Subject Headings], skin and connective tissue diseases, Diseases::Skin and Connective Tissue Diseases::Connective Tissue Diseases::Lupus Erythematosus, Cutaneous::Lupus Erythematosus, Discoid [Medical Subject Headings], Systemic lupus erythematosus, Lupus eritematoso discoide, Cumulative dose, General Medicine, Humanos, Chemicals and Drugs::Polycyclic Compounds::Steroids::Pregnanes::Pregnadienes::Pregnadienetriols::Prednisolone::Methylprednisolone [Medical Subject Headings], Cohort, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Immunologic Factors::Immunosuppressive Agents [Medical Subject Headings], Glucocorticoid, medicine.drug, medicine.medical_specialty, Antimaláricos, Immunology, Diseases::Skin and Connective Tissue Diseases::Connective Tissue Diseases::Lupus Erythematosus, Systemic::Lupus Nephritis [Medical Subject Headings], Brief Communication, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiparasitic Agents::Antiprotozoal Agents::Antimalarials [Medical Subject Headings], Systemic Lupus Erythematosus, Disease activity, 03 medical and health sciences, Internal medicine, Lupus eritematoso sistémico, medicine, Corticosteroids, Metilprednisolona, Glucocorticoides, Disease Activity, 030203 arthritis & rheumatology, business.industry, Diseases::Skin and Connective Tissue Diseases::Connective Tissue Diseases::Lupus Erythematosus, Systemic [Medical Subject Headings], Inmunosupresores, Pulso arterial, medicine.disease, Chemicals and Drugs::Polycyclic Compounds::Steroids::Pregnanes::Pregnadienes::Pregnadienediols::Prednisone [Medical Subject Headings], Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Adrenal Cortex Hormones::Glucocorticoids [Medical Subject Headings], 030104 developmental biology, Endocrinology, Prednisona, Observational study, business
Abstract: Aim: To study the influence of prednisone dose during the first month after systemic lupus erythematosus (SLE) diagnosis (prednisone-1) on glucocorticoid burden during the subsequent 11 months (prednisone-2-12). Methods: 223 patients from the Registro Espanol de Lupus Eritematoso Sisternico inception cohort were studied. The cumulative dose of prednisone-1 and prednisone-2-12 were calculated and recoded into a four-level categorical variable: no prednisone, low dose (up to 7.5 mg/day), medium dose (up to 30 mg/day) and high dose (over 30 mg/day). The association between the cumulative prednisone-1 and prednisone-2-12 doses was tested. We analysed whether the four level prednisone-1 categorical variable was an independent predictor of an average dose >7.5 mg/day of prednisone-2-12. Adjusting variables included age, immunosuppressives, antimalarials, methyl-prednisolone pulses, lupus nephritis and baseline SLE Disease Activity Index (SLEDAI). Results: Within the first month, 113 patients (51%) did not receive any prednisone, 24 patients (11%) received average low doses, 46 patients (21%) received medium doses and 40 patients (18%) received high doses. There was a strong association between prednisone-1 and prednisone-2-12 dose categories (p7.5 mg/day, while patients receiving low dose prednisone-1 were not (adjusted OR 1.4, 95% CI 0. 0.38 to 5.2). If the analysis was restricted to the 158 patients with a baseline SLEDAI of >= 6, the model did not change. Conclusion: The dose of prednisone during the first month after the diagnosis of SLE is an independent predictor of prednisone burden during the following 11 months., This study was supported by the Spanish Society of Internal Medicine.
Published: 2016

36. Rheumatoid arthritis response to treatment across IgG1 allotype - anti-TNF incompatibility: a case-only study

Author: Miguel Ferrer, Ann W. Morgan, Beatriz Joven, John D. Isaacs, Theologia Sarafidou, Enrique Raya, Rafael Cáliz, Javier Narváez, Ariana Montes, Ana Márquez, C. Magro, Javier Martín, F. Navarro-Sarabia, Moreira Vf, María del Carmen Ordóñez, Lara Valor, Alejandro Balsa, Antonio Fernández-Nebro, Juan José Alegre-Sancho, Arturo Rodríguez de la Serna, Anne Barton, Rosa Garcia-Portales, Manuel J. Moreno-Ramos, Antonio Gonzalez, Anthony G. Wilson, Francisco J. Blanco, Patricia Carreira, Yiannis Vasilopoulos, Juan J. Gomez-Reino, Darren Plant, Berta Magallares, Juan D. Cañete, Eva Perez-Pampin, Dora Pascual-Salcedo, Universitat de Barcelona, Instituto de Salud Carlos III, European Commission, [Montes,A, Perez-Pampin,E] Laboratorio de Investigacion 10 and Rheumatology Unit, Instituto de Investigacion Sanitaria - Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain. [Navarro-Sarabia, F, Moreira,V] Rheumatology Unit, Hospital Universitario Virgen Macarena, Sevilla, Spain. [Rodríguez de la Serna,A, Magallares,B] Rheumatology Unit, Hospital Santa Creu e San Pau, Barcelona, Spain. [Vasilopoulos,Y, Sarafidou,T] Department of Biochemistry and Biotechnology, University of Thessaly, Larissa, Greece. [Fernández-Nebro,A, Ordóñez,MC] Servicio de Reumatología, HRU Carlos Haya, Universidad de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain. [Narváez,J] Department of Rheumatology, Hospital Universitario de Bellvitge, Barcelona, Spain. [Cañete,Jd] Rheumatology Unit, Hospital Clinic, Barcelona, Spain. [Marquez,A] Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Granada, Spain. [Pascual-Salcedo,D] Department of Immunology, Instituto de Investigación Hospital Universitario La Paz, Hospital La Paz, Madrid, Spain. [Joven,B, Carreira,P] Department of Rheumatology, Hospital 12 de Octubre, Madrid, Spain. [Moreno-Ramos,MJ] Department of Rheumatology, Hospital Virgen de la Arrixaca, Murcia, Spain. [Caliz,R, Ferrer,NA] Rheumatology Unit, Hospital Universitario Virgen de las Nieves, Granada, Spain. [Garcia-Portales,R] Department of Rheumatology, Hospital Virgen de la Victoria, Málaga, Spain. [Blanco,FJ] Rheumatology Department, Instituto de Investigacion Biomedica-Complejo Hospitalario Universitario A Coruna, Department of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain. [Magro,C, Raya,E] Department of Rheumatology, Hospital Clínico San Cecilio, Granada, Spain. [Valor,L] Rheumatology Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain. [Alegre-Sancho,JJ] Department of Rheumatology, Hospital Doctor Peset, Valencia, Spain. [Balsa,A] Department of Rheumatology, Instituto de Investigación Hospital Universitario La Paz, Hospital Universitario La Paz, Madrid, Spain.[Martin,J] Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Granada, Spain. [Plant,D] NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK. [Isaacs,J] Musculoskeletal Research Group, Institute of Cellular Medicine, The Medical School, Newcastle University, National Institute for Health Research Newcastle Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, Newcastle upon Tyne, Newcastle, UK. [Morgan,AW] Leeds Institute of Rheumatic and Musculoskeletal Medicine, St. James's University Hospital, University of Leeds, NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK. [Barton,A] NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Arthritis Research UK-Centre for Genetics and Genomics, The University of Manchester, Manchester, UK. [Wilson,AG] University College Dublin, Dublin, Ireland. [Gómez-Reino,JJ] Laboratorio de Investigacion 10 and Rheumatology Unit, Instituto de Investigacion Sanitaria - Hospital Clinico Universitario de Santiago, Department of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain. [Gonzalez,A] Laboratorio de Investigacion 10 and Rheumatology Unit, Instituto de Investigacion Sanitaria - Hospital Clinico Universitario de Santiago, Laboratorio Investigacion 10, Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain., Funding was provided by grants PI11/01048, PI12/01909 and by RETICS Program, RD08/0075/0019 and RD12/0009/0008 (RIER) of the Instituto de Salud Carlos III (Spain) that are partially financed by the European Regional Development Fund of the European Union, UAM. Departamento de Medicina, and Instituto de Investigación Sanitaria Hospital Universitario de La Paz (IdiPAZ)
Subjects: Male, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines::Tumor Necrosis Factors [Medical Subject Headings], Immunoglobulin G, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Arthritis, Rheumatoid, Immunology and Allergy, Single nucleotide, skin and connective tissue diseases, biology, IgG1 allotype, Drugs, Enfermedades reumáticas, Middle Aged, Allotype, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines::Monokines::Tumor Necrosis Factor-alpha [Medical Subject Headings], Articulaciones, Treatment Outcome, Estudi de casos, Rheumatoid arthritis, Diseases::Musculoskeletal Diseases::Rheumatic Diseases [Medical Subject Headings], Arthritis rheumatoid, Antirheumatic Agents, Teràpia genètica, Tumor necrosis factor alpha, Female, Phenomena and Processes::Genetic Phenomena::Genotype [Medical Subject Headings], Antibody, Medicaments, medicine.drug, Research Article, Adult, musculoskeletal diseases, medicine.medical_specialty, Genotype, Medicina, Anatomy::Musculoskeletal System::Skeleton::Joints [Medical Subject Headings], Immunology, Molecular Sequence Data, Artritis reumatoide, Polymorphism, Single Nucleotide, Gene therapy, Rheumatology, Internal medicine, Diseases::Musculoskeletal Diseases::Joint Diseases::Arthritis::Arthritis, Rheumatoid [Medical Subject Headings], medicine, Adalimumab, Humans, Polymorphism, Immunoglobulin Allotypes, Base Sequence, business.industry, Tumor Necrosis Factor-alpha, medicine.disease, Infliximab, Factor de necrosis tumoral alfa, Treatment, biology.protein, Case studies, business, Genotipo
Abstract: Montes, Ariana et al., [Introduction] We have hypothesized that incompatibility between the G1m genotype of the patient and the G1m1 and G1m17 allotypes carried by infliximab (INX) and adalimumab (ADM) could decrease the efficacy of these anti-tumor necrosis factor (anti-TNF) antibodies in the treatment of rheumatoid arthritis (RA)., [Methods] The G1m genotypes were analyzed in three collections of patients with RA totaling 1037 subjects. The first, used for discovery, comprised 215 Spanish patients. The second and third were successively used for replication. They included 429 British and Greek patients and 393 Spanish and British patients, respectively. Two outcomes were considered: change in the Disease Activity Score in 28 joint (ΔDAS28) and the European League Against Rheumatism (EULAR) response criteria., [Results] An association between less response to INX and incompatibility of the G1m1,17 allotype was found in the discovery collection at 6 months of treatment (P = 0.03). This association was confirmed in the replications (P = 0.02 and 0.08, respectively) leading to a global association (P = 0.001) that involved a mean difference in ΔDAS28 of 0.4 units between compatible and incompatible patients (2.3 ± 1.5 in compatible patients vs. 1.9 ± 1.5 in incompatible patients) and an increase in responders and decrease in non-responders according to the EULAR criteria (P = 0.03). A similar association was suggested for patients treated with ADM in the discovery collection, but it was not supported by replication., [Conclusions] Our results suggest that G1m1,17 allotypes are associated with response to INX and could aid improved therapeutic targeting in RA., Funding was provided by grants PI11/01048, PI12/01909 and by RETICS Program, RD08/0075/0019 and RD12/0009/0008 (RIER) of the Instituto de Salud Carlos III (Spain) that are partially financed by the European Regional Development Fund of the European Union.
Published: 2015

37. Patients' and physicians' preferences for type 2 diabetes mellitus treatments in Spain and Portugal: a discrete choice experiment

Author: Morillas, Carlos, Feliciano, Rosa, Catalina, Pablo Fernández, Ponte, Carla, Botella, Marta, Rodrigues, João, Esmatjes, Enric, Lafita, Javier, Lizán, Luis, Llorente, Ignacio, Morales, Cristóbal, Navarro-Pérez, Jorge, Orozco-Beltran, Domingo, Paz, Silvia, Ramirez de Arellano, Antonio, Cardoso, Cristina, Tribaldos Causadias, Maribel, Novo Nordisk A/S, [Morillas,C] Hospital Universitario Dr Peset, Valencia, Spain. [Feliciano,R] USF São Domingos, Santarém, Portugal. [Fernández Catalina,P] Hospital Montecelo de Pontevedra, Galicia, Spain. [Ponte,C] USF Porta do Sol, Matosinhos, Portugal. [Botella,M] Hospital Universitario Principe de Asturias, Madrid, Spain. [Rodrigues,J] USF Serra da Lousã, Lousã, Portugal. [Esmatjes,E] Hospital Clinic, Barcelona, Spain. [Lafita,J] Hospital de Navarra, Navarra, Spain. [Lizán,L, Paz,S, Tribaldos Causadias,M] Outcomes'10, Universidad Jaume I, Castellón, Spain. [Llorente,I] Hospital Universitario Nuestra Señora de la Candelaria, Canarias, Spain. [Morales,C] Hospital Universitario Virgen de la Macarena, Sevilla, Spain. [Navarro-Pérez,J] INCLIVA, CIBERESP, Universidad de Valencia, Valencia, Spain. [Orozco-Beltran,D] Sociedad Española de Medicina Familiar y Comunitaria, Valencia, Spain. [Ramirez de Arellano,A] Novo Nordisk EU-HEOR Europe, Madrid, Spain. [Cardoso,C] Novo Nordisk, Lisbon, Portugal., and This project was sponsored by Novo Nordisk A/S.
Subjects: Geographicals::Geographic Locations::Europe::Portugal [Medical Subject Headings], cardiovascular risk, HbA1c, endocrine system diseases, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Physical Examination::Body Constitution::Body Weights and Measures::Body Mass Index [Medical Subject Headings], Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Hypoglycemia [Medical Subject Headings], Disciplines and Occupations::Health Occupations::Medicine::Public Health [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Named Groups::Persons::Occupational Groups::Health Personnel::Physicians [Medical Subject Headings], HbA(1c), HbA, Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Body Weight::Body Weight Changes::Weight Loss [Medical Subject Headings], Diseases::Cardiovascular Diseases [Medical Subject Headings], preferences, Geographicals::Geographic Locations::Europe::Spain [Medical Subject Headings], diabetes, nutritional and metabolic diseases, Peso corporal, weight, Pérdida de peso, Health Care::Health Care Facilities, Manpower, and Services::Health Facilities::Ambulatory Care Facilities [Medical Subject Headings], Diabetes mellitus tipo 2, Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Signs and Symptoms, Digestive::Nausea [Medical Subject Headings], hypoglycemia, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Models, Statistical::Logistic Models [Medical Subject Headings], Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Body Weight [Medical Subject Headings], Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Diabetes Mellitus::Diabetes Mellitus, Type 2 [Medical Subject Headings], Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Hypoglycemic Agents [Medical Subject Headings], Enfermedades cardiovasculares, Hipoglucemia, willingness to pay, Check Tags [Medical Subject Headings], discrete choice model
Abstract: Objective: To assess Spanish and Portuguese patients' and physicians' preferences regarding type 2 diabetes mellitus (T2DM) treatments and the monthly willingness to pay (WTP) to gain benefits or avoid side effects. Methods: An observational, multicenter, exploratory study focused on routine clinical practice in Spain and Portugal. Physicians were recruited from multiple hospitals and outpatient clinics, while patients were recruited from eleven centers operating in the public health care system in different autonomous communities in Spain and Portugal. Preferences were measured via a discrete choice experiment by rating multiple T2DM medication attributes. Data were analyzed using the conditional logit model. Results: Three-hundred and thirty (n=330) patients (49.7% female; mean age 62.4 [SD: 10.3] years, mean T2DM duration 13.9 [8.2] years, mean body mass index 32.5 [6.8] kg/m(2), 41.8% received oral + injected medication, 40.3% received oral, and 17.6% injected treatments) and 221 physicians from Spain and Portugal (62% female; mean age 41.9 [SD: 10.5] years, 33.5% endocrinologists, 66.5% primary-care doctors) participated. Patients valued avoiding a gain in bodyweight of 3 kg/6 months (WTP: (sic)68.14 [95% confidence interval: 54.55-85.08]) the most, followed by avoiding one hypoglycemic event/month (WTP: (sic)54.80 [23.29-82.26]). Physicians valued avoiding one hypoglycemia/week (WTP: (sic)287.18 [95% confidence interval: 160.31-1,387.21]) the most, followed by avoiding a 3 kg/6 months gain in bodyweight and decreasing cardiovascular risk (WTP: (sic)166.87 [88.63-843.09] and (sic)154.30 [98.13-434.19], respectively). Physicians and patients were willing to pay (sic)125.92 (73.30-622.75) and (sic)24.28 (18.41-30.31), respectively, to avoid a 1% increase in glycated hemoglobin, and (sic)143.30 (73.39-543.62) and (sic)42.74 (23.89-61.77) to avoid nausea. Conclusion: Both patients and physicians in Spain and Portugal are willing to pay for the health benefits associated with improved diabetes treatment, the most important being to avoid hypoglycemia and gaining weight. Decreased cardiovascular risk and weight reduction became the third most valued attributes for physicians and patients, respectively.
Published: 2015

38. Frequency and characteristics of familial melanoma in Spain: the FAM-GEM-1 Study

Author: Miguel-Ángel Idoate-Gastearena, José Pedro Vaqué, Javier Valdivia, Jordi Rubió-Casadevall, Miguel Angel Berciano Guerrero, Nuria Blázquez Sánchez, Luis De la Cruz-Merino, JM Caminal, Elísabeth Pérez Ruiz, Javier Martin-Broto, PEDRO REDONDO, Jose Luis González Larriba, Ana Arance, CARMEN GUILLEN PONCE, Rosa M Marti, Jose Luis Rodriguez-Peralto, Francisco Aya, Eduardo Nagore, Clara Olier-Garate, Salvador Martín Algarra, Delvys Rodriguez-Abreu, Ivan Marquez-Rodas, Virginia Palomar Coloma, Aram Boada, Jose Luis Perez-Gracia, Alfonso Martín Carnicero, Spanish Multidisciplinary Group of Melanoma (GEM)., [Márquez-Rodas,I] Servicio de Oncología Médica, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain. [Martín González,M] Servicio de Dermatología, Hospital Ramón y Cajal, Madrid, Spain. [Nagore,E] Servicio de Dermatología, Instituto Valenciano de Oncología, Valencia, Spain. [Gómez-Fernández,C, Maseda,R] Servicio de Dermatología, Hospital La Paz, Madrid, Spain. [Avilés-Izquierdo,JA] Servicio de Dermatología, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain. [Maldonado-Seral,C] Servicio de Dermatología, Hospital Universitario Central de Asturias, Oviedo, Spain. [Soriano,V] Servicio de Oncología Médica, Instituto Valenciano de Oncología, Valencia, Spain. [Majem-Tarruella,M] Servicio de Oncología Médica, Hospital de Sant Pau, Barcelona, Spain. [Maseda,R]Servicio de Oncología Médica, Hospital de San Pedro, Logroño, Spain. [Puertolas,T] Servicio de Oncología, Hospital Universitario Miguel Servet, Zaragoza, Spain. [Godoy,E] Servicio de Dermatología, Hospital de Cabueñes, Gijon, Spain. [Cerezuela,P] Servicio de Oncología Médica, Hospital General Universitario Santa Lucia, Cartagena, Spain. [Ochoa de Olza,M] Servicio de Oncología Médica, Instituto Catalan de Oncología, Hospitalet, Spain. [Campos,B] Servicio de Oncología Médica, Hospital Lucus Augusti, Lugo, Spain. [Pérez-Ruiz,E] Servicio de Oncología Médica, Hospital Costa del Sol, Marbella, Spain. [Soria,A] Servicio de Oncología Médica, Hospital Ramón y Cajal, Madrid, Spain. [Gil-Arnaiz,I] Servicio de Oncología Medica, Hospital Reina Sofía, Tudela, Spain. [Gonzalez-Cao,M] Servico de Oncología Médica, Instituto Dexeus, Barcelona, Spain. [Galvez,E] Servicio de Oncología Médica, Hospital de Elda, Alicante, Spain. [Arance,A] Servicio de Oncología Medica, Hospital Clinic, Barcelona, Spain. [Belon,J] Servicio de Oncología Médica, Clínica Oncogranada, Granada, Spain. [Cruz-Merino,L de la] Servicio de Oncología Médica, Hospital Virgen de la Macarena, Sevilla, Spain. [Martín-Algarra,S] Departamento de Oncología, Clínica Universidad de Navarra, Pamplona, Spain., and Universitat de Barcelona
Subjects: Male, Oncology, Pathology, Skin Neoplasms, Multivariate analysis, lcsh:Medicine, Disease, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Named Groups::Persons::Population Groups::Ethnic Groups::Hispanic Americans [Medical Subject Headings], Risk Factors, Family history, lcsh:Science, Melanoma, Pancreas cancer, Factores de Riesgo, Geographicals::Geographic Locations::Europe::Spain [Medical Subject Headings], Univariate analysis, Multidisciplinary, Incidence, Incidence (epidemiology), Pronóstico, Dermatología, Middle Aged, Multiple melanoma, Familial melanoma, Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Cycle::Cell Division::Cell Nucleus Division::Mitosis [Medical Subject Headings], Female, Research Article, medicine.medical_specialty, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Analysis of Variance::Multivariate Analysis [Medical Subject Headings], The FAM-GEM-1, Mitosis, Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Germ Cell and Embryonal::Neuroectodermal Tumors::Neuroendocrine Tumors::Melanoma [Medical Subject Headings], Internal medicine, Pancreatic cancer, Diseases::Skin and Connective Tissue Diseases::Skin Diseases::Photosensitivity Disorders::Sunburn [Medical Subject Headings], medicine, Humans, Genetic Predisposition to Disease, Espanya, Risk factor, Quemadura Solar, neoplasms, Càncer de pàncrees, Amilial melanoma patients, business.industry, lcsh:R, Disciplines and Occupations::Health Occupations::Medicine::Dermatology [Medical Subject Headings], medicine.disease, Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Pancreatic Neoplasms [Medical Subject Headings], Spain, Multivariate Analysis, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis [Medical Subject Headings], lcsh:Q, business, Neoplasias Pancreáticas
Abstract: Introduction Familial history of melanoma is a well-known risk factor for the disease, and 7% melanoma patients were reported to have a family history of melanoma. Data relating to the frequency and clinical and pathological characteristics of both familial and non-familial melanoma in Spain have been published, but these only include patients from specific areas of Spain and do not represent the data for the whole of Spain. Patients and methods An observational study conducted by the Spanish Group of Melanoma (GEM) analyzed the family history of patients diagnosed with melanoma between 2011 and 2013 in the dermatology and oncology departments. Results In all, 1047 patients were analyzed, and 69 (6.6%) fulfilled criteria for classical familial melanoma (two or more first-degree relatives diagnosed with melanoma). Taking into account other risk factors for familial melanoma, such as multiple melanoma, pancreatic cancer in the family or second-degree relatives with melanoma, the number of patients fulfilling the criteria increased to 165 (15.8%). Using a univariate analysis, we determined that a Breslow index of less than 1 mm, negative mitosis, multiple melanoma, and a history of sunburns in childhood were more frequent in familial melanoma patients, but a multivariate analysis revealed no differences in any pathological or clinical factor between the two groups. Conclusions Similar to that observed in other countries, familial melanoma accounts for 6.6% of melanoma diagnoses in Spain. Although no differences in the multivariate analysis were found, some better prognosis factors, such as Breslow index, seem more frequent in familial melanoma, which reflect a better early detection marker and/or a different biological behavior.
Published: 2015

39. Classification and clinical behavior of blastic plasmacytoid dendritic cell neoplasms according to their maturation-associated immunophenotypic profile

Author: Pilar Alejandra Saiz Martínez, Berta Valverde, Margarida Lima, Alberto Orfao, Josefa Marco Buadesa, Belén Vidriales, Silvia Inês Ferreira, Maria Dolores Caballero, António Silva Rodrigues, Jorge Candeias, Neus Villamor, Sérgio Almeida, Ana Ferrer, Francisco Ruiz-Cabello, Antonio López, Amparo Sempere, Julia Almeida, Lourdes Martín-Martín, Junta de Castilla y León, European Commission, Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, [Martín-Martín,L, López,A, Orfao,A, Almeida,J] Cancer Research Centre (IBMCC, USAL-CSIC), Institute for Biomedical Research of Salamanca (IBSAL) and Department of Medicine and Cytometry Service, University of Salamanca (USAL), Salamanca, Spain. [Vidriales,B, Caballero,MD] Hematology Department and IBSAL, University Hospital of Salamanca, Salamanca, Spain. [Silva Rodrigues,A] Hematology Department, Hospital de Santo António dos Capuchos, Lisboa, Portugal. [Ferreira,SI] Santa Luzia Medical Laboratory, Florianópolis, SC, Brazil. [Lima,M] Clinical Hematology Department, Hospital de Santo António, Porto, Portugal. [Almeida,S] Hematology Department, Hospital Universidade de Coimbra, Coimbra, Portugal. [Valverde,B] Hematology Department, Hospital Nacional de Niños Dr. Carlos Sáenz Herrera, San José, Costa Rica. [Martínez,P] Hematology Department, Hospital 12 de Octubre, Madrid, Spain. [Ferrer,A] Pathology Department, Hospital del Mar, Barcelona. IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain. [Candeias,J] Immunology Department, Hospital São João, Porto, Portugal. [Ruíz-Cabello,F] Clinical Analysis and Immunology Department, Hospital Virgen de las Nieves, Granada, Spain. [Marco Buadesa,J] Hematology Department, Hospital General de Castellón, Castellón, Spain. [Sempere,A] Hematology Department, University Hospital La Fé, Valencia, Spain. [Villamor,N] Hospital Clinic, Barcelona, Spain., and This work was supported by grants RD06/0020/0035 and RD12/0036/0048 from RETICS (Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain and Fondos FEDER) and grant EDU/878/2004 from Junta de Castilla y León and Fondo Social Europeo.
Subjects: Male, Pathology, Phenomena and Processes::Genetic Phenomena::Phenotype [Medical Subject Headings], Skin Neoplasms, Lymphoma, Diseases::Neoplasms::Neoplasms by Site::Hematologic Neoplasms [Medical Subject Headings], blastic plasmacytoid dendritic cell neoplasm, CD34, ComputingMilieux_LEGALASPECTSOFCOMPUTING, Plasmacytoid dendritic cell, Diseases::Neoplasms::Neoplasms by Histologic Type::Lymphoma [Medical Subject Headings], Plasmacitoma, Células Dendríticas, maturation profile, hemic and lymphatic diseases, Flow cytometry, acute leukemia, Citometría de Flujo, Child, Aged, 80 and over, Acute leukemia, Age Factors, Leucèmia, Middle Aged, Leucemia-Linfoma Linfoblástico de Células Precursoras, Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Plasma Cell::Plasmacytoma [Medical Subject Headings], Leukemia, Linfoma, Oncology, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Transplantation::Cell Transplantation::Stem Cell Transplantation [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Cytological Techniques::Cell Separation::Flow Cytometry [Medical Subject Headings], Hematologic Neoplasms, Female, Stem cell, Fenotipo, Research Paper, Adult, medicine.medical_specialty, Diseases::Neoplasms::Neoplasms by Histologic Type::Leukemia [Medical Subject Headings], Maturation profile, lymphoma, Biology, Immunophenotyping, Blastic plasmacytoid dendritic cell neoplasm, Precursor cell, Diseases::Neoplasms::Neoplasms by Histologic Type::Leukemia::Leukemia, Lymphoid::Precursor Cell Lymphoblastic Leukemia-Lymphoma [Medical Subject Headings], medicine, Humans, Leucemia, Limfomes -- Classificació, Aged, Anatomy::Cells::Antigen-Presenting Cells::Dendritic Cells [Medical Subject Headings], flow cytometry, Trasplante de Células Madre, Dendritic Cells, medicine.disease, Transplantation
Abstract: This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al., Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare subtype of leukemia/lymphoma, whose diagnosis can be difficult to achieve due to its clinical and biological heterogeneity, as well as its overlapping features with other hematologic malignancies. In this study we investigated whether the association between the maturational stage of tumor cells and the clinico-biological and prognostic features of the disease, based on the analysis of 46 BPDCN cases classified into three maturation-associated subgroups on immunophenotypic grounds. Our results show that blasts from cases with an immature plasmacytoid dendritic cell (pDC) phenotype exhibit an uncommon CD56- phenotype, coexisting with CD34+ non-pDC tumor cells, typically in the absence of extramedullary (e.g. skin) disease at presentation. Conversely, patients with a more mature blast cell phenotype more frequently displayed skin/extramedullary involvement and spread into secondary lymphoid tissues. Despite the dismal outcome, acute lymphoblastic leukemia-type therapy (with central nervous system prophylaxis) and/or allogeneic stem cell transplantation appeared to be the only effective therapies. Overall, our findings indicate that the maturational profile of pDC blasts in BPDCN is highly heterogeneous and translates into a wide clinical spectrum -from acute leukemia to mature lymphoma-like behavior-, which may also lead to variable diagnosis and treatment., This work was supported by grants RD06/0020/0035 and RD12/0036/0048 from RETICS (Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain and Fondos FEDER) and grant EDU/878/2004 from Junta de Castilla y León and Fondo Social Europeo.
Published: 2015

40. No Evidence of Association between Common Autoimmunity STAT4 and IL23R Risk Polymorphisms and Non-Anterior Uveitis

Author: Manuel Díaz-Llopis, Miguel Cordero-Coma, Ana Márquez, Blanca Molins, Ricardo Blanco, María José del Rio, J. Cañal, Marina Begoña Gorroño-Echebarría, Javier Martín, Agustin Martinez-Berriotxoa, David Díaz Valle, María Carmen Cenit, Norberto Ortego-Centeno, José Manuel Martín-Villa, Enrique de Ramón, José Luis García Serrano, Esperanza Pato, Alfredo Adán, Alejandro Fonollosa, [Cénti,MC, Márquez,A, Martín,J] Instituto de Parasitología y Biomedicina López-Neyra, IPBLN, CSIC, Granada, Spain. [Cordero-Coma,M] Ophthalmology Department, Hospital de León, León, Spain. [Gorroño-Echebarría, MB] Ophthalmology Department, Hospital Universitario Principe de Asturias, Alcalá de Henares, Spain. [Fonollosa,A, Martínez-Berriotxoa,A] Internal Medicine Department, Hospital de Cruces, Bilbao, Spain. [Adán,A, and Molins,B] Ophthalmology Department, Hospital Clinic, Barcelona, Spain. [DÍaz Valle,D] Ophthalmology Department, Hospital Clínico San Carlos, Madrid, Spain. [Pato,E] Rheumatology Department, Hospital Clínico San Carlos, Madrid, Spain. [Blanco,R] Rheumatology Department, Hospital Marqués de Valdecilla, IFIMAV, Santander, Spain. [Cañal,J] Ophthalmology Department, Hospital Marqués de Valdecilla, Santander, Spain. [Díaz-Llopis,M] Ophthalmology Department, Hospital Universitario La Fe, Valencia, Spain. [García Serrano,JL] Ophthalmology Department, Hospital Clínico San Cecilio, Granada, Spain. [Ramón de, E] Internal Medicine Department, Hospital Carlos Haya, Málaga, Spain. [Río del,MJ] Ophthalmology Department, Hospital Carlos Haya, Málaga, Spain. [Martín-Villa,JM] Immunology Department, Facultad de Medicina, Universidad Complutense de Madrid, Spain. [Ortego-Centeno,N] Internal Medicine Department, Hospital Clínico San Cecilio, Granada, Spain.
Subjects: Phenomena and Processes::Immune System Phenomena::Immunity::Autoimmunity [Medical Subject Headings], Male, Polimorfismo de nucleótido simple, Polimorfismo genético, Autoimmunity, Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], medicine.disease_cause, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Gene Frequency, Genotype, STAT4, Multidisciplinary, Receptores de interleucina, Middle Aged, STAT4 Transcription Factor, Phenotype, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Immunologic::Receptors, Cytokine::Receptors, Interleukin [Medical Subject Headings], Medicine, Female, Phenomena and Processes::Genetic Phenomena::Genotype [Medical Subject Headings], Alelos, Uveitis, Research Article, Adult, musculoskeletal diseases, Science, Check Tags::Male [Medical Subject Headings], Autoinmunidad, Biology, Polymorphism, Single Nucleotide, Factores de transcripción, IL23R protein, human, Named Groups::Persons::Age Groups::Adult [Medical Subject Headings], medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, Allele, Allele frequency, Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Alleles [Medical Subject Headings], Alleles, Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single Nucleotide [Medical Subject Headings], Polymorphism, Genetic, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intracellular Signaling Peptides and Proteins::Adaptor Proteins, Signal Transducing::STAT Transcription Factors [Medical Subject Headings], Receptors, Interleukin, Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic [Medical Subject Headings], medicine.disease, Uveítis, Check Tags::Female [Medical Subject Headings], Immunology, Genotipo, Diseases::Eye Diseases::Uveal Diseases::Uveitis [Medical Subject Headings]
Abstract: OBJECTIVE: STAT4 and IL23R loci represent common susceptibility genetic factors in autoimmunity. We decided to investigate for the first time the possible role of different STAT4/IL23R autoimmune disease-associated polymorphisms on the susceptibility to develop non-anterior uveitis and its main clinical phenotypes. METHODS: Four functional polymorphisms (rs3821236, rs7574865, rs7574070, and rs897200) located within STAT4 gene as well as three independent polymorphisms (rs7517847, rs11209026, and rs1495965) located within IL23R were genotyped using TaqMan® allelic discrimination in a total of 206 patients with non-anterior uveitis and 1553 healthy controls from Spain. RESULTS: No statistically significant differences were found when allele and genotype distributions were compared between non-anterior uveitis patients and controls for any STAT4 (rs3821236: P=0.39, OR=1.12, CI 95%=0.87-1.43; rs7574865: P=0.59 OR=1.07, CI 95%=0.84-1.37; rs7574070: P=0.26, OR=0.89, CI 95%=0.72-1.10; rs897200: P=0.22, OR=0.88, CI 95%=0.71-1.08;) or IL23R polymorphisms (rs7517847: P=0.49, OR=1.08, CI 95%=0.87-1.33; rs11209026: P=0.26, OR=0.78, CI 95%=0.51-1.21; rs1495965: P=0.51, OR=0.93, CI 95%=0.76-1.15). CONCLUSION: Our results do not support a relevant role, similar to that described for other autoimmune diseases, of IL23R and STAT4 polymorphisms in the non-anterior uveitis genetic predisposition. Further studies are needed to discard a possible weak effect of the studied variant.
Published: 2013

41. HLA and non-HLA genes in Behçet¿s disease: a multicentric study in the Spanish population

Author: Miguel A. González-Gay, P. Fanlo, Genaro Graña-Gil, María Francisca González-Escribano, Norberto Ortego-Centeno, Ana Celia Barnosi-Marín, Javier Martín, Juan Sánchez-Bursón, Gerard Espinosa, Marta Conde-Jaldón, Roser Solans, Antonio Núñez-Roldán, Teresa Camps, José Raúl García-Lozano, M.A. Montes-Cano, María Jesús Castillo-Palma, Lourdes Ortiz-Fernández, Santos Castañeda, [Montes Cano,A, Conde-Jaldón,M, García-Lozano,J, Ortiz-Fernández,L, Núñez-Roldán,A, González-Escribano,MF] Servicio de Inmunología, IBiS, Hospital Universitario Virgen del Rocío/CSIC/ Universidad de Sevilla, Spain. [Ortego-Centeno,N] Servicio de Medicina Interna, Hospital Clínico San Cecilio, Granada, Spain. [Castillo-Palma,MJ] Servicio de Medicina Interna, Hospital Universitario Virgen del Rocío, Sevilla, Spain. [Espinosa,G] Servicio de Enfermedades Autoinmunes, Hospital Clinic, Barcelona, Spain. [Graña-Gil,G] Servicio de Reumatología, CHU A Coruña, Spain. [González-Gay,MA] Servicio de Reumatología, Hospital Marques de Valdecilla, Santander, Spain. [Barnosi-Marín,AC] Servicio de Medicina Interna, Hospital Torrecárdenas, Almería, Spain. [Solans,R] Servicio de Medicina Interna, Hospital Vall d’Hebron, Barcelona, Spain. [Fanlo,P] Servicio de Medicina Interna, Hospital Virgen del Camino, Pamplona, Spain. [Camps,T] Servicio de Medicina Interna, Hospital Carlos Haya, Málaga, Spain. [Castañeda,S] Servicio de Reumatología, Hospital de la Princesa, Madrid, Spain. [Sánchez-Bursón,J] Servicio de Reumatología, Hospital de Valme, Sevilla, Spain. [Martín,J] IPB López Neyra, Granada, Spain., Fondo de Investigaciones Sanitarias (10/1701), Fondos FEDER, Plan Andaluz de Investigación (CTS-0197 and CTS-180), Red Enfermedades Inflamatorias y Reumáticas RD08/0075/0013 and Consejería de Salud de la Junta de Andalucía (PI0411/2010). LOF is the recipient of a fellowship (FI11/00547). The authors thank Asociación Andaluza de Enfermedades Autoinmunes (AADEA) and all patients and donors enrolled in the present study for their cooperation. Also, the authors thank the following public Spanish institutions for their participation in this study: Servicio Andaluz de Salud (Hospitales Torrecárdenas, Almería, Clínico San Cecilio, Granada, and Carlos Haya, Málaga, and Virgen del Rocío and Valme, Sevilla), Servei Catalá de la Salut (Clinic and Vall d’Hebron hospitals, Barcelona), Servizo Galego de Saude (Complejo Hospitalario Universitario, A Coruña), Servicio Cántabro de Salud (Hospital Marqués de Valdecilla, Santander), Servicio Navarro de Salud (Hospital Virgen del Camino, Pamplona), Servicio Montes-Cano et al. Arthritis Research & Therapy 2013, 15:R145
Subjects: Male, Antígeno HLA-B35, Candidate gene, Genome-wide association study, Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Glycoproteins::Membrane Glycoproteins::Histocompatibility Antigens Class I::HLA-A Antigens [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Chemicals and Drugs::Biological Factors::Antigens::Antigens, Surface::Histocompatibility Antigens::HLA Antigens::HLA-B Antigens::HLA-B35 Antigen [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Receptores de Interleucina, Gene Frequency, Risk Factors, HLA Antigens, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical::Models, Statistical::Logistic Models [Medical Subject Headings], Immunology and Allergy, Diseases::Stomatognathic Diseases::Mouth Diseases::Behcet Syndrome [Medical Subject Headings], Geographicals::Geographic Locations::Europe::Spain [Medical Subject Headings], Genetics, education.field_of_study, Behcet Syndrome, Antígenos HLA-B, Antígenos HLA-A, Middle Aged, Interleukin-10, Chemicals and Drugs::Biological Factors::Antigens::Antigens, Surface::Histocompatibility Antigens::HLA Antigens::HLA-B Antigens [Medical Subject Headings], Chemicals and Drugs::Biological Factors::Antigens::Antigens, Surface::Histocompatibility Antigens::HLA Antigens::HLA-B Antigens::HLA-B51 Antigen [Medical Subject Headings], HLA-B51 Antigen, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Immunologic::Receptors, Cytokine::Receptors, Interleukin [Medical Subject Headings], Female, Chemicals and Drugs::Biological Factors::Antigens::Antigens, Surface::Histocompatibility Antigens::HLA Antigens [Medical Subject Headings], Interleucina-10, Phenomena and Processes::Genetic Phenomena::Genotype [Medical Subject Headings], Antígeno HLA-B51, Research Article, HLA-B57 antigen, Adult, Antígeno HLA-B57, Genotype, Immunology, Population, Check Tags::Male [Medical Subject Headings], Single-nucleotide polymorphism, Human leukocyte antigen, Biology, Polymorphism, Single Nucleotide, Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Susceptibility::Genetic Predisposition to Disease [Medical Subject Headings], Rheumatology, IL23R protein, human, Named Groups::Persons::Age Groups::Adult [Medical Subject Headings], HLA-B Antigens, Humans, Genetic Predisposition to Disease, education, Allele frequency, Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single Nucleotide [Medical Subject Headings], HLA-A Antigens, Antígeno HLA, Receptors, Interleukin, Minor allele frequency, Logistic Models, Check Tags::Female [Medical Subject Headings], Spain, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines::Interleukins::Interleukin-10 [Medical Subject Headings], HLA-B35 Antigen, Phenomena and Processes::Genetic Phenomena::Gene Frequency [Medical Subject Headings], Genome-Wide Association Study
Abstract: Introduction According to genome wide association (GWA) studies as well as candidate gene approaches, Behçet’s disease (BD) is associated with human leukocyte antigen (HLA)-A and HLA-B gene regions. The HLA-B51 has been consistently associated with the disease, but the role of other HLA class I molecules remains controversial. Recently, variants in non-HLA genes have also been associated with BD. The aims of this study were to further investigate the influence of the HLA region in BD and to explore the relationship with non-HLA genes recently described to be associated in other populations. Methods This study included 304 BD patients and 313 ethnically matched controls. HLA-A and HLA-B low resolution typing was carried out by PCR-SSOP Luminex. Eleven tag single nucleotide polymorphisms (SNPs) located outside of the HLA-region, previously described associated with the disease in GWA studies and having a minor allele frequency in Caucasians greater than 0.15 were genotyped using TaqMan assays. Phenotypic and genotypic frequencies were estimated by direct counting and distributions were compared using the χ2 test. Results In addition to HLA-B*51, HLA-B*57 was found as a risk factor in BD, whereas, B*35 was found to be protective. Other HLA-A and B specificities were suggestive of association with the disease as risk (A*02 and A*24) or protective factors (A*03 and B*58). Regarding the non-HLA genes, the three SNPs located in IL23R and one of the SNPs in IL10 were found to be significantly associated with susceptibility to BD in our population. Conclusion Different HLA specificities are associated with Behçet’s disease in addition to B*51. Other non-HLA genes, such as IL23R and IL-10, play a role in the susceptibility to the disease., This work was supported by Fondo de Investigaciones Sanitarias (10/1701), Fondos FEDER, Plan Andaluz de Investigación (CTS-0197 and CTS-180), Red Enfermedades Inflamatorias y Reumáticas RD08/0075/0013 and Consejería de Salud de la Junta de Andalucía (PI0411/2010). LOF is the recipient of a fellowship (FI11/00547).
Published: 2013
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42. Evaluation of the IL2/IL21, IL2RA and IL2RB genetic variants influence on the endogenous non-anterior uveitis genetic predisposition

Author: Manuel Díaz-Llopis, Agustin Martinez-Berriotxoa, David Díaz Valle, Alfredo Adán, Miguel Cordero-Coma, Ricardo Blanco, Ana Márquez, Marina Begoña Gorroño Echebarría, Norberto Ortego-Centeno, José Manuel Martín-Villa, Alejandro Fonollosa, Enrique de Ramón, Javier Martín, Victor Llorenç, María José del Rio, María Carmen Cenit, José Luis García Serrano, J. Cañal, [Cénit,MC, Márquez,A, Martín,J] Instituto de Parasitología y Biomedicina López-Neyra, IPBLN, CSIC, Armilla, Granada, Spain. [Cordero-Coma,M] Ophthalmology Department, Hospital de León, Spain. [Fonollosa,A, Martínez-Berriotxoa,A] Internal Medicine Department, Hospital de Cruces, Bilbao, Spain. [Adán,A, and Llorenç,V] Ophthalmology Department, Hospital Clinic, Barcelona, Spain. [Díaz Valle,D] Ophthalmology Department, Hospital Clínico San Carlos, Madrid, Spain. [Blanco,R] Rheumatology Department, Hospital Marqués de Valdecilla, IFIMAV, Santander, Spain. [Cañal,J] Ophthalmology Department, Hospital Marqués de Valdecilla, Santander, Spain. [Díaz-Llopis,M] Ophthalmology Department, Hospital Universitario La Fe, Valencia, Spain. [García Serrano,JL] Ophthalmology Department, Hospital Clínico San Cecilio, Granada, Spain. [Ramón,E de] Internal Medicine Department, Hospital Carlos Haya, Málaga, Spain. [Rio,MJ del] Ophthalmology Department, Hospital Carlos Haya, Málaga, Spain. [Gorroño- Echebarría,MB] Ophthalmology Department, Hospital Universitario Principe de Asturias, Alcalá de Henares, Spain. [Martín-Villa,JM] Immunology Department, Facultad de Medicina, Universidad Complutense de Madrid, Spain. [Ortego-Centeno,N] Internal Medicine Department, Hospital Clínico San Cecilio, Granada, Spain.
Subjects: Male, Polimorfismo de nucleótido simple, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines::Interleukins [Medical Subject Headings], Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Statistics as Topic::Models, Statistical [Medical Subject Headings], Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], medicine.disease_cause, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Immunologic::Receptors, Cytokine::Receptors, Interleukin::Receptors, Interleukin-2::Interleukin-2 Receptor beta Subunit [Medical Subject Headings], Autoimmunity, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Modelos estadísticos, Genotype, Genetics(clinical), Genetics (clinical), IL21, Genetics, 0303 health sciences, Predisposición genética a la enfermedad, Middle Aged, 3. Good health, Association study, Female, Phenomena and Processes::Genetic Phenomena::Genotype [Medical Subject Headings], Phenomena and Processes::Genetic Phenomena::Genetic Variation [Medical Subject Headings], Uveitis, Research Article, Adult, Interleucina-2, Check Tags::Male [Medical Subject Headings], Biology, Variación genética, Subunidad alfa del receptor de interleucina-2, Polymorphism, Single Nucleotide, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], 03 medical and health sciences, Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Susceptibility::Genetic Predisposition to Disease [Medical Subject Headings], Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines::Interleukins::Interleukin-2 [Medical Subject Headings], Genetic variation, Genetic predisposition, medicine, Genetic susceptibility, Named Groups::Persons::Age Groups::Adult [Medical Subject Headings], Humans, Genetic Predisposition to Disease, Allele, Named Groups::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Alleles, Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Alleles [Medical Subject Headings], Aged, 030304 developmental biology, IL2RB, Models, Statistical, IL2, Polymorphism, Genetic, IL2RA, Interleukins, Interleukin-2 Receptor alpha Subunit, Genetic Variation, Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic [Medical Subject Headings], medicine.disease, Human genetics, Interleukin-2 Receptor beta Subunit, Uveítis, stomatognathic diseases, Check Tags::Female [Medical Subject Headings], Case-Control Studies, Immunology, 030221 ophthalmology & optometry, Interleukin-2, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Immunologic::Receptors, Cytokine::Receptors, Interleukin::Receptors, Interleukin-2::Interleukin-2 Receptor alpha Subunit [Medical Subject Headings], Polymorphisms, Genotipo, Diseases::Eye Diseases::Uveal Diseases::Uveitis [Medical Subject Headings]
Abstract: Background Recently, different genetic variants located within the IL2/IL21 genetic region as well as within both IL2RA and IL2RB loci have been associated to multiple autoimmune disorders. We aimed to investigate for the first time the potential influence of the IL2/IL21, IL2RA and IL2RB most associated polymorphisms with autoimmunity on the endogenous non-anterior uveitis genetic predisposition. Methods A total of 196 patients with endogenous non-anterior uveitis and 760 healthy controls, all of them from Caucasian population, were included in the current study. The IL2/IL21 (rs2069762, rs6822844 and rs907715), IL2RA (2104286, rs11594656 and rs12722495) and IL2RB (rs743777) genetic variants were genotyped using TaqMan® allelic discrimination assays. Results A statistically significant difference was found for the rs6822844 (IL2/IL21 region) minor allele frequency in the group of uveitis patients compared with controls (P- value=0.02, OR=0.64 CI 95%=0.43-0.94) although the significance was lost after multiple testing correction. Furthermore, no evidence of association with uveitis was detected for the analyzed genetic variants of the IL2RA or IL2RB loci. Conclusion Our results indicate that analyzed IL2/IL21, IL2RA and IL2RB polymorphisms do not seem to play a significant role on the non-anterior uveitis genetic predisposition although further studies are needed in order to clear up the influence of these loci on the non-anterior uveitis susceptibility., The authors thank Sofía Vargas, Sonia Rodríguez and Gema Robledo (from Instituto de Parasitología y Biomedicina ‘López-Neyra’, CSIC, Spain) for their excellent technical assistance, and all the patients and healthy controls for kindly accepting their essential collaboration. Banco Nacional de ADN (University of Salamanca, Spain) and Biobanco Vasco para la Investigación (Fundación Vasca de Innovación e Investigación Sanitarias, Bizkaia, Spain) are thanked for supplying part of the samples.
Published: 2013

43. Lack of association between the protein tyrosine phosphatase non-receptor type 22 R263Q and R620W functional genetic variants and endogenous non-anterior uveitis

Author: Carmen Cenit, Maria, Marquez, Ana, Cordero-Coma, Miguel, Fonollosa, Alejandro, Llorenc, Victor, Artaraz, Joseba, Diaz Valle, David, Blanco, Ricardo, Canal, Joaquin, Salom, David, Garcia Serrano, Jose Luis, Ramon, Enrique, Jose Del Rio, Maria, Begona Gorrono-Echebarria, Marina, Manuel Martin-Villa, Jose, Molins, Blanca, Ortego-Centeno, Norberto, Javier Martin, [Cénit,MC, Márquez,A, Martín,J] Instituto de Parasitología y Biomedicina López-Neyra, IPBLN, CSIC, Granada, Spain. [Cordero-Coma,M] Ophthalmology Department, Hospital de León, León, Spain. [Fonollosa,A, and Artaraz,J] Ophthalmology Department, Hospital de Cruces, Bilbao, Spain. [Llorenç,V] Ophthalmology Department, Hospital Clínic, Barcelona, Spain. [Díaz Valle, D] Ophthalmology Department, Hospital Clínico San Carlos, Madrid, Spain. [Blanco,R] Rheumatology Department, Hospital Marqués de Valdecilla, IFIMAV, Santander, Spain. [Cañal,J] Ophthalmology Department, Hospital Marqués de Valdecilla, IFIMAV, Santander, Spain. [Salom,D] Ophthalmology Department, Hospital Universitario La Fe, Valencia, Spain. [García Serrano,JL] Ophthalmology Department, Hospital Clínico San Cecilio, Granada, Spain. [Ramon,E de] Internal Medicine Department, Hospital Carlos Haya, Málaga, Spain. [Rio,MJ del] Ophthalmology Department, Hospital Carlos Haya, Málaga, Spain. [Gorroño-Echebarría,MB] Ophthalmology Department, Hospital Universitario Principe de Asturias, Alcalá de Henares, Spain. [Martín-Villa,JM] Immunology Department, Facultad de Medicina, Universidad Complutense de Madrid, Spain. [Molins,B] Instituto de Investigaciones Biomédicas, IDIBAPS, Hospital Clinic, Barcelona, Spain. [Ortego-Centeno,N] Internal Medicine Department, Hospital Clínico San Cecilio, Granada, Spain.
Subjects: Male, Proteína tirosina fosfatasa no receptora de tipo 22, España, Health Care::Population Characteristics::Demography [Medical Subject Headings], Check Tags::Male [Medical Subject Headings], Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Proteínas mutantes, Polymorphism, Single Nucleotide, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Genetic Association Studies [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Intracellular Signaling Peptides and Proteins::Protein Tyrosine Phosphatases, Non-Receptor::Protein Tyrosine Phosphatase, Non-Receptor Type 22 [Medical Subject Headings], Gene Frequency, Humans, Demografía, Genetic Predisposition to Disease, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Mutant Proteins [Medical Subject Headings], Diseases::Eye Diseases::Uveal Diseases::Uveitis::Panuveitis::Uveitis, Anterior [Medical Subject Headings], Alleles, Genetic Association Studies, Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Alleles [Medical Subject Headings], Demography, Geographicals::Geographic Locations::Europe::Spain [Medical Subject Headings], Phenomena and Processes::Genetic Phenomena::Genetic Processes::Mutagenesis::Amino Acid Substitution [Medical Subject Headings], Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single Nucleotide [Medical Subject Headings], Estudios de casos y controles, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], Estudios de asociación genética, Predisposición genética a la enfermedad, Protein Tyrosine Phosphatase, Non-Receptor Type 22, Middle Aged, Uveitis, Anterior, Polimorfismo de nucleótido único, Phenomena and Processes::Genetic Phenomena::Genotype::Genetic Predisposition to Disease [Medical Subject Headings], eye diseases, Frecuencia génica, Uveítis anterior, Amino Acid Substitution, Check Tags::Female [Medical Subject Headings], Spain, Case-Control Studies, Female, Mutant Proteins, Alelos, Phenomena and Processes::Genetic Phenomena::Gene Frequency [Medical Subject Headings], Research Article
Abstract: Journal Article; OBJECTIVE Endogenous uveitis is a major cause of visual loss mediated by the immune system. The protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene encodes a lymphoid-specific phosphatase that plays a key role in T-cell receptor (TCR) signaling. Two independent functional missense single nucleotide polymorphisms (SNPs) located within the PTPN22 gene (R263Q and R620W) have been associated with different autoimmune disorders. We aimed to analyze for the first time the influence of these PTPN22 genetic variants on endogenous non-anterior uveitis susceptibility. METHODS We performed a case-control study of 217 patients with endogenous non-anterior uveitis and 718 healthy controls from a Spanish population. The PTPN22 polymorphisms (rs33996649 and rs2476601) were genotyped using TaqMan allelic discrimination assays. The allele, genotype, carriers, and allelic combination frequencies were compared between cases and controls with χ(2) analysis or Fisher's exact test. RESULTS Our results showed no influence of the studied SNPs in the global susceptibility analysis (rs33996649: allelic P- value=0.92, odds ratio=0.97, 95% confidence interval=0.54-1.75; rs2476601: allelic P- value=0.86, odds ratio=1.04, 95% confidence interval=0.68-1.59). Similarly, the allelic combination analysis did not provide additional information. CONCLUSIONS Our results suggest that the studied polymorphisms of the PTPN22 gene do not play an important role in the pathophysiology of endogenous non-anterior uveitis. Yes
Published: 2013

44. A multicenter study confirms CD226 gene association with systemic sclerosis-related pulmonary fibrosis

Author: Bossini-Castillo, L., Simeon, C.P., Beretta, L., Broen, J.C., Vonk, M.C., Rios-Fernandez, R., Espinosa, G., Carreira, P., Camps, M.T., Castillo, M.J., Gonzalez-Gay, M.A., Beltran, E., Freire, M.D., Narvaez, J., Tolosa, C., Witte, T., Kreuter, A., Schuerwegh, A.J., Hoffmann-Vold, A.M., Hesselstrand, R., Lunardi, C., Laar, J.M. van, Chee, M.M., Herrick, A., Koeleman, B.P.C., Denton, C.P., Fonseca, C., Radstake, T.R.D.J., Martin, J., Spanish Scleroderma Grp, The Spanish Scleroderma Group, [Bossini-Castillo,L, Martín,J] Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, Granada, Spain. [Simeon,CP] Servicio de Medicina Interna, Hospital Valle de Hebron, Barcelona, Spain. [Beretta,L] IRCCS Fondazione Policlinico-Mangiagalli-Regina Elena and University of Milan, Allergy, Clinical Immunology and Rheumatology, Milan, Italy. [Broen,JC, Vonk,MC] Department of Rheumatology, Radboud University Nijmegen Medical CentreNijmegen, The Netherlands. [Ríos-Fernández,R] Servicio de Medicina Interna, Hospital Clínico Universitario, Granada, Spain. [Espinosa,G] Servicio de Enfermedades Autoinmunes, Hospital Clinic, Barcelona, Spain. [Carreira,P] Servicio de Reumatología, Hospital 12 de Octubre, Madrid, Spain. [Camps,MT] Servicio de Medicina Interna, Hospital Carlos Haya, Málaga, Spain. [Castillo,MJ] Servicio de Medicina Interna, Hospital Virgen del Rocío, Sevilla, Spain. [González-Gay,MA] Servicio de Reumatología, Hospital Universitario Marqués de Valdecilla, IFIMAV, Santander, Spain. [Beltran,E] Servicio de Reumatología, Hospital del Doctor Peset Aleixandre, Valencia, Spain. [Freire,M del C] Unidad Trombosis y Vasculitis, Servicio de Medicina Interna, Hospital Xeral-Complexo Hospitalario Universitario de Vigo, Vigo, Spain. [Narváez,J] Servicio de Reumatología, Hospital Universitario de Bellvitge, Barcelona, Spain. [Tolosa,C] Servicio de Medicina Interna, Hospital Parc Taulí, Sabadell, Spain. [Witte,T] Hannover Medical School, Hannover, Germany. [Kreuter,A] Ruhr University of Bochum, Bochum, Germany. [Schuerwegh,AJ] Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. [Hoffmann-Vold,A-M] Department of Rheumatology, Rikshospitalet, Oslo University Hospital, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway. [Hesselstrand,R] Department of Rheumatology, Lund University, Lund, Sweden. [Lunardi,C] Department of Medicine, Università degli Studi di Verona Verona, Italy. [Van Laar,JM] Institute of Cellular Medicine, Newcastle University, NewcastleUK. [Chee,MM] Centre for Rheumatic Diseases, Glasgow Royal Infirmary, Glasgow, UK. [Herrick,A] Arthritis Research UK Epidemiology Unit, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK. [Koeleman,BPC] Section Complex Genetics, Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands. [Denton,CP, Fonseca,C] Centre for Rheumatology, Royal Free and University College Medical School, University College London, London, UK. [Radstake,TRDJ] Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands., This work was supported by the following grants: GENFER from the Spanish Society of Rheumatology, SAF2009-11110 from the Spanish Ministry of Science, CTS-4977 from Junta de Andalucía, Spain, in part by Redes Temáticas de Investigación Cooperativa Sanitaria Program, RD08/0075 (RIER) from Instituto de Salud Carlos III (ISCIII), Spain and by Fondo Europeo de Desarrollo Regional (FEDER). The VIDI laureate from the Dutch Association of Research (NWO) and Dutch Arthritis Foundation (National Reumafonds). The Orphan Disease Program grant from the European League Against Rheumatism (EULAR). The Dutch Diabetes Research Foundation (grant 2008.40.001) and the Dutch Arthritis Foundation (Reumafonds, grant NR 09-1-408). DFG WI 1031/6.1. This study was also funded by PI-0590-2010, Consejería de Salud, Junta de Andalucía, Spain., and Universitat de Barcelona
Subjects: Antigens, Differentiation, T-Lymphocyte, Male, systemic sclerosis, CD226 gene, Autoimmune diseases, Pulmonary Fibrosis, Genome-wide association study, Chemicals and Drugs::Biological Factors::Biological Markers::Antigens, Differentiation::Antigens, Differentiation, T-Lymphocyte [Medical Subject Headings], GWAS, Genoma humà, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Genetic Association Studies [Medical Subject Headings], Diseases::Skin and Connective Tissue Diseases::Connective Tissue Diseases::Scleroderma, Systemic [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Cohort Studies, Pulmonary fibrosis, Immunology and Allergy, Antígenos de diferenciación de linfocitos T, Malalties autoimmunitàries, Fibrosi pulmonar, Infection and autoimmunity Auto-immunity, transplantation and immunotherapy [NCMLS 1], Evaluation of complex medical interventions Auto-immunity, transplantation and immunotherapy [NCEBP 2], Female, Phenomena and Processes::Genetic Phenomena::Genotype [Medical Subject Headings], Phenomena and Processes::Genetic Phenomena::Genetic Variation [Medical Subject Headings], Research Article, Genotype, Estudios de cohortes, Fibrosis pulmonar, Esclerodermia sistémica, Immunology, Check Tags::Male [Medical Subject Headings], Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Rheumatology, Genetic variation, medicine, Genetic predisposition, Humans, SNP, Diseases::Respiratory Tract Diseases::Lung Diseases::Pulmonary Fibrosis [Medical Subject Headings], Genetic Association Studies, Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single Nucleotide [Medical Subject Headings], Scleroderma, Systemic, Human genome, Estudios de asociación genética, Haplotype, Autoantibody, Genetic Variation, medicine.disease, Scleroderma (Disease), Check Tags::Female [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Esclerodèrmia, Genotipo
Abstract: Introduction CD226 genetic variants have been associated with a number of autoimmune diseases and recently with systemic sclerosis (SSc). The aim of this study was to test the influence of CD226 loci in SSc susceptibility, clinical phenotypes and autoantibody status in a large multicenter European population. Methods A total of seven European populations of Caucasian ancestry were included, comprising 2,131 patients with SSc and 3,966 healthy controls. Three CD226 single nucleotide polymorphisms (SNPs), rs763361, rs3479968 and rs727088, were genotyped using Taqman 5'allelic discrimination assays. Results Pooled analyses showed no evidence of association of the three SNPs, neither with the global disease nor with the analyzed subphenotypes. However, haplotype block analysis revealed a significant association for the TCG haplotype (SNP order: rs763361, rs34794968, rs727088) with lung fibrosis positive patients (P Bonf = 3.18E-02 OR 1.27 (1.05 to 1.54)). Conclusion Our data suggest that the tested genetic variants do not individually influence SSc susceptibility but a CD226 three-variant haplotype is related with genetic predisposition to SSc-related pulmonary fibrosis., This work was supported by the following grants: JM was funded by GEN-FER from the Spanish Society of Rheumatology, SAF2009-11110 from the Spanish Ministry of Science, CTS-4977 from Junta de Andalucía, Spain, in part by Redes Temáticas de Investigación Cooperativa Sanitaria Program, RD08/0075 (RIER) from Instituto de Salud Carlos III (ISCIII), Spain and by Fondo Europeo de Desarrollo Regional (FEDER).
Published: 2012

45. Analysis of the association between CD40 and CD40 ligand polymorphisms and systemic sclerosis

Author: Teruel, María, Simeón Aznar, Carmen Pilar, Broen, Jasper C., Vonk, Madelon C., Carreira, Patricia, Camps García, María Teresa, García-Portales, Rosa, Delgado-Frías, Esmeralda, Gallego, Maria, Espinosa Garriga, Gerard, Spanish Scleroderma Study Group (SSSG), Beretta, Lorenzo, Airó, Paolo, Lunardi, Claudio, Riemekasten, Gabriela, Witte, Torsten, Krieg, Thomas, Kreuter, Alexander, Distler, Jörg H.V., Hunzelmann, Nicolas, Koeleman, Bobby P. C., Voskuyl, Alexandre E., Schuerwegh, Annemie J., González-Gay, Miguel A., Radstake, Timothy R.D.J., Martín, Javier, Narváez García, Francisco Javier, Rheumatology, CCA - Immuno-pathogenesis, Universitat de Barcelona, The Spanish Scleroderma Group, [Teruel,M, Martin,J] Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSICGranada, SpainArmilla (Granada), Spain. [Simeon,CP] Department of Internal Medicine, Hospital Valle de Hebron, Barcelona, Spain. [Broen,J, Vonk,MC] Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. [Carreira,P] Department of Rheumatology, Hospital 12 de Octubre, Madrid, Spain. [Camps,MT] Department of Internal Medicine, Hospital Carlos Haya, Málaga, Spain. [García-Portales,R] Department of Rheumatology, Hospital Virgen de la Victoria, Málaga, Spain. [Delgado-Frías,E] Department of Rheumatology, Hospital Universitario de Canarias, La Cuesta, San Cristóbal de La Laguna, Tenerife, Canarias, Spain. [Gallego,M] Department of Internal Medicine, Hospital Central de Asturias, Oviedo, Spain. [Espinosa,G] Department of Autoimmune Diseases, Hospital Clinic, Barcelona, Spain. [Beretta,L] Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca’Granda Ospedale Maggiore Policlinico. University of Milan, Milan, Italy. [Airó,P] Rheumatology Unit and Chair, Spedali Civili, Università degli Studi, Brescia, Italy. [Lunardi,C] Department of Medicine, Policlinico GB Rossi, Università degli studi di Verona, Verona, Italy. [Riemekasten,G] Department of Rheumatology and Clinical Immunology, Charité University Hospital and German Rheumatism Research Centre, a Leibniz Institute, Berlin, Germany. [Witte,T] Clinic for Immunology and Rheumatology Medical School, Hannover, Germany. [Krieg,T, and Hunzelmann,N] Department of Dermatology, University of Cologne, Germany. [Kreuter,A] Department of Dermatology, Allergology, and Venereology, Ruhr University of Bochum, Bochum, Germany. [Distler,JHW] Department of Internal Medicine 3, Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany. [Koeleman,BP] Section Complex Genetics, Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands. [Voskuy,AE] Department of Rheumatology, VU University Medical Center, Amsterdam, The Netherlands. [Schuerwegh,AJ] Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. [González-Gay,MA] Department of Rheumatology, Hospital Universitario Marques de Valdecilla, IFIMAV, Santander, Spain. [Radstake,TRDJ] Department of Rheumatology and Clinical Immunology, University Utrecht Medical Center Utrecht, The Netherlands.
Subjects: systemic sclerosis, Autoimmune diseases, Genome-wide association study, CD40, CD40L, GWAS, Serology, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Pulmonary fibrosis, Genotype, Immunology and Allergy, Diseases::Skin and Connective Tissue Diseases::Skin Diseases::Scleroderma, Systemic [Medical Subject Headings], skin and connective tissue diseases, Giant cell arteritis, 0303 health sciences, Chemicals and Drugs::Biological Factors::Antigens::Antigens, Surface::Antigens, Differentiation::Antigens, CD::Antigens, CD40 [Medical Subject Headings], Malalties autoimmunitàries, integumentary system, Predisposición genética a la enfermedad, Fibrosi pulmonar, Phenomena and Processes::Genetic Phenomena::Genotype::Genetic Predisposition to Disease [Medical Subject Headings], Phenotype, Infection and autoimmunity Auto-immunity, transplantation and immunotherapy [NCMLS 1], Humanos, 3. Good health, 030220 oncology & carcinogenesis, Evaluation of complex medical interventions Auto-immunity, transplantation and immunotherapy [NCEBP 2], Phenomena and Processes::Genetic Phenomena::Genotype [Medical Subject Headings], Research Article, medicine.medical_specialty, Esclerodermia sistémica, Immunology, CD40 Ligand, Single-nucleotide polymorphism, Polymorphism, Single Nucleotide, 03 medical and health sciences, Rheumatology, Internal medicine, medicine, Humans, antígenos CD40, Genetic Predisposition to Disease, CD40 Antigens, Gene, Arteritis de cèl·lules gegants, 030304 developmental biology, Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single Nucleotide [Medical Subject Headings], Scleroderma, Systemic, business.industry, Chemicals and Drugs::Biological Factors::Antigens::Antigens, Surface::Antigens, Differentiation::Antigens, CD::CD40 Ligand [Medical Subject Headings], medicine.disease, Ligando CD40, Scleroderma (Disease), Polimorfismo de Nucleótido Simple, Esclerodèrmia, business, Genotipo
Abstract: Introduction The aim of the present study was to investigate the possible role of CD40 and CD40 ligand (CD40LG) genes in the susceptibility and phenotype expression of systemic sclerosis (SSc). Methods In total, 2,670 SSc patients and 3,245 healthy individuals from four European populations (Spain, Germany, The Netherlands, and Italy) were included in the study. Five single-nucleotide polymorphisms (SNPs) of CD40 (rs1883832, rs4810485, rs1535045) and CD40LG (rs3092952, rs3092920) were genotyped by using a predesigned TaqMan allele-discrimination assay technology. Meta-analysis was assessed to determine whether an association exists between the genetic variants and SSc or its main clinical subtypes. Results No evidence of association between CD40 and CD40LG genes variants and susceptibility to SSc was observed. Similarly, no significant statistical differences were observed when SSc patients were stratified by the clinical subtypes, the serologic features, and pulmonary fibrosis. Conclusions Our results do not suggest an important role of CD40 and CD40LG gene polymorphisms in the susceptibility to or clinical expression of SSc., This work was supported by the following grants. JM was funded by SAF2009-11110 from the Spanish Ministry of Science, by CTS-4977 and PI-0590-2010 from Junta de Andalucía, and by RETICS Program, RD08/0075 (RIER) from Instituto de Salud Carlos III (ISCIII), within the VI PN de I+D+i 2008-2011 (FEDER). T.R.D.J.R. was funded by the VIDI laureate from the Dutch Association of Research (NWO) and Dutch Arthritis Foundation (National Reumafonds). JM and TRDJR were sponsored by the Orphan Disease Program grant from the European League Against Rheumatism (EULAR). TW was awarded grants by DFG WI 1031/6.1 and DFG KFO 250 TP03. MT was supported by Spanish Ministry of Science through the program Juan de la Cierva (JCI-2010-08227).
Published: 2012

46. Central nervous system involvement at first relapse in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline monochemotherapy without intrathecal prophylaxis

Author: Concha Rivas, José González, Marcos González, Miguel A. Sanz, Guillermo Deben, Jordi Esteve, Javier de la Serna, Pau Montesinos, Inmaculada Pérez, Salut Brunet, Isolda Fernández, Joaquín Díaz-Mediavilla, Chelo Rayon, Silvia Negri, Mar Tormo, José D. González, Vicente Rubio, Maricruz Viguria, Virginia Prates, Juan Bergua, Bob Löwenberg, Hematology, [Montesinos,P, Sanz, MA] Hospital Universitario La Fe, Valencia, Spain. [Díaz-Mediavilla,J] Hospital Clínico San Carlos, Madrid, Spain. [Debén,G] Hospital Juan Canalejo, La Coruña, Spain. [Prates,V] Instituto de Trasplante de Médula Ósea, Buenos Aires, Argentina. [Tormo,M] Hospital Clínico Universitario, Valencia, Spain. [Rubio,V] Hospital General, Jerez de la Frontera, Spain. [Pérez,I] Hospital Universitario Virgen de la Victoria, Málaga, Spain. [Fernández,I] Fundaleu, Buenos Aires, Argentina. [Viguria,M] Hospital de Navarra, Pamplona, Spain. [Rayón,C] Hospital Central de Asturias, Oviedo, Spain. [González,J] Hospital Universitario Virgen del Rocío, Sevilla, Spain.[Serna,J de la] Hospital 12 de Octubre, Madrid, Spain. [Esteve,J] Hospital Clinic, Barcelona, Spain. [Bergua,JM] Hospital San Pedro de Alcántara, Cáceres, Spain. [Rivas,C] Hospital General, Alicante, Spain. [González,M] Hospital Universitario, Salamanca, Spain. [González,JD] Hospital Insular, Las Palmas, Spain. [Negri,S] Hospital Carlos Haya, Málaga, Spain. [Brunet,S] Hospital Sant Pau, Barcelona, Spain. [Lowenberg,B] Erasmus University Medical Center, Rotterdam, The Netherlands., and This study was supported in part by the Fundación para la Investigación hospital Universitario La Fe-Ayudas Bancaja (grant 2006/0137), Red Temática de Investigación Cooperativa en Cáncer (RD06/0020/0031).
Subjects: Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Aromatic::Polycyclic Hydrocarbons, Aromatic::Naphthacenes::Anthracyclines::Daunorubicin::Idarubicin [Medical Subject Headings], Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Recurrence [Medical Subject Headings], Male, Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], idarubicin, Gastroenterology, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Central Nervous System Neoplasms, Leukemia, Promyelocytic, Acute, Recurrence, Risk Factors, Cumulative incidence, Antibiotics, Antineoplastic, Hematology, Middle Aged, all-trans retinoic acid, Leukemia, medicine.anatomical_structure, Named Groups::Persons::Age Groups::Adolescent [Medical Subject Headings], Female, medicine.drug, Acute promyelocytic leukemia, Adult, central nervous system relapse, medicine.medical_specialty, Diseases::Neoplasms::Neoplasms by Histologic Type::Leukemia::Leukemia, Myeloid::Leukemia, Myeloid, Acute [Medical Subject Headings], Anthracycline, Adolescent, Central nervous system, Check Tags::Male [Medical Subject Headings], Tretinoin, Neoplasias del sistema nervioso central, Central nervous system disease, Internal medicine, Named Groups::Persons::Age Groups::Adult [Medical Subject Headings], medicine, Idarubicin, Humans, Named Groups::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Letters to the Editor, Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Acyclic::Alkenes::Polyenes::Carotenoids::Retinoids [Medical Subject Headings], Leucemia promielocítica aguda, Aged, Antibióticos antineoplásicos, business.industry, prognostic factors, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents::Antibiotics, Antineoplastic [Medical Subject Headings], acute promyelocytic leukemia, medicine.disease, Surgery, Diseases::Neoplasms::Neoplasms by Site::Nervous System Neoplasms::Central Nervous System Neoplasms [Medical Subject Headings], Check Tags::Female [Medical Subject Headings], business
Abstract: Background The prevalence of and risk factors for central nervous system recurrence in patients with acute promyelocytic leukemia are not well established and remain a controversial matter. Design and Methods Between 1996 and 2005, 739 patients with newly diagnosed acute promyelocytic leukemia enrolled in two consecutive trials (PETHEMA LPA96 and LPA99) received induction therapy-with all-trans retinoic acid and idarubicin. Consolidation therapy comprised three courses of anthracycline monochemotherapy (LPA96), with all-trans retinoic acid and reinforced doses of idarubicin in patients with an intermediate or high risk of relapse (LPA99). Central nervous system prophylaxis was not given. Results Central nervous system relapse was documented in 11 patients. The 5-year cumulative incidence of central nervous system relapse was 1.7% (LPA96 3.2% and LPA99 1.2%; p=0.09). The cumulative incidence was 0%, 0.8%, and 5.5% in low-, intermediate-, and high-risk patients, respectively. Relapse risk score (p=0.0001) and the occurrence of central nervous system hemorrhage during induction (5-year cumulative incidence 18.7%, p=0.006) were independent risk factors for central nervous system relapse. Conclusions This study shows a low incidence of central nervous system relapse in patients with acute promyelocytic leukemia following therapy with all-trans retinoic acid and anthracycline without specific central nervous system prophylaxis. Central nervous system relapse was significantly associated with high white blood cell counts and prior central nervous system hemorrhage, which emerged as independent prognostic factors.
Published: 2009

47. Use of Hy's Law and a New Composite Algorithm to Predict Acute Liver Failure in Patients With Drug-Induced Liver Injury

Author: M. Isabel Lucena, Fernando Bessone, Martín Prieto, Camilla Stephens, Inmaculada Medina–Cáliz, Mercedes Robles Diaz, Andres Gonzalez Jimenez, M. Carmen Fernández, Marco Arrese, Ana González, Nelia Hernández, Neil Kaplowitz, Miguel Bruguera, Eugenia Ulzurrun, Miguel Jimenez–Perez, Manuel Romero Gomez, Raúl J. Andrade, [Robles-Díaz, M, Lucena, MI, Stephens, C, Medina-Cáliz, I, González-Jiménez, A, Ulzurrun, E, González, AF, Andrade, RJ] Unidad de Gestión Clínica de Enfermedades Digestivas, Servicio de Farmacología Clínica, Hospital Universitario Virgen de la Victoria, Málaga, Spain. [Robles-Díaz, M, Romero-Gómez, M, Bruguera, M, Prieto, M, Andrade, RJ] Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain. [Kaplowitz, N] University of Southern California Research Center for Liver Diseases, Keck School of Medicine, Los Angeles, CA, United States. [Fernandez, MC] Servicio de Farmacia, Hospital de Torrecardenas, Almería, Spain. [ Romero-Gómez, M] Unidad de Gestión Clínica de Enfermedades Digestivas, Hospital Universitario de Valme, Sevilla, Spain. [Jiménez-Pérez, M] Unidad de Gestión Clínica de Enfermedades Digestivas, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario Carlos Haya, Málaga, Spain. [Bruguera, M] Instituto de Enfermedades Digestivas y Metabolismo, Hospital Clinic, Barcelona, Spain. [Prieto, M] Unidad de Gestión Clínica de Enfermedades Digestivas, Hospital la Fe, Valencia, Spain. [Bessone, F] Facultad de Ciencias Médicas, Servicio de Gastroenterología y Hepatología, Hospital Provincial del Centenario, Rosario, Argentina. [Hernández, N] Hospital de Clínicas Clínica de Gastroenterología, Facultad de Medicina, Universidad de la Republica, Montevideo, Uruguay., and Supported by a research grant (Fondo de Investigación Sanitaria, PI12-00620), the Agencia Española del Medicamento, and the Innovative Medicines Initiative Safer and Faster Evidence-based Translation consortium (Framework Programme for Research and Technological Development (FP-7) grant agreement number 523 705, IMI-2008-T5). CIBERehd is funded by the Instituto de Salud Carlos III.
Subjects: Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies::Retrospective Studies [Medical Subject Headings], Named Groups::Persons::Age Groups::Adult::Aged::Aged, 80 and over [Medical Subject Headings], Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Fallo hepático agudo, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Bilirrubina, chemistry.chemical_compound, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Models, Statistical [Medical Subject Headings], Alanina transaminasa, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Epidemiologic Factors::Comorbidity [Medical Subject Headings], Ictericia, Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Esterases::Phosphoric Monoester Hydrolases::Alkaline Phosphatase [Medical Subject Headings], Liver injury, Diseases::Digestive System Diseases::Liver Diseases::Drug-Induced Liver Injury [Medical Subject Headings], Idiosyncratic Hepatotoxicity, Progression, Algoritmos, Marcadores biológicos, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Epidemiologic Factors::Sex Factors [Medical Subject Headings], digestive, oral, and skin physiology, Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Nitrogenous Group Transferases::Transaminases::Alanine Transaminase [Medical Subject Headings], Gastroenterology, Jaundice, Comorbilidad, Sensibilidad y especificidad, Factores sexuales, Named Groups::Persons::Age Groups::Adolescent [Medical Subject Headings], Predictive value of tests, Alkaline phosphatase, Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Azoles::Pyrroles::Tetrapyrroles::Bile Pigments::Bilirubin [Medical Subject Headings], medicine.symptom, Algorithm, Factores de riesgo, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Statistics as Topic::Sensitivity and Specificity [Medical Subject Headings], Named Groups::Persons::Age Groups::Adult::Young Adult [Medical Subject Headings], Bilirubin, Diseases::Digestive System Diseases::Liver Diseases::Hepatic Insufficiency::Liver Failure::Liver Failure, Acute [Medical Subject Headings], Prognostic Risk Factor, Hy's law, Valor predictivo de las pruebas, Named Groups::Persons::Age Groups::Adult [Medical Subject Headings], Chemicals and Drugs::Biological Factors::Biological Markers [Medical Subject Headings], medicine, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Epidemiologic Research Design::Sensitivity and Specificity::Predictive Value of Tests [Medical Subject Headings], Niños, Named Groups::Persons::Age Groups::Child [Medical Subject Headings], Hepatology, Receiver operating characteristic, business.industry, Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Nitrogenous Group Transferases::Transaminases::Aspartate Aminotransferases [Medical Subject Headings], Retrospective cohort study, medicine.disease, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Hyperbilirubinemia::Jaundice [Medical Subject Headings], chemistry, Enfermedad hepática inducida por drogas, Prediction, Information Science::Information Science::Computing Methodologies::Algorithms [Medical Subject Headings], business
Abstract: Journal Article; BACKGROUND & AIMS Hy's Law, which states that hepatocellular drug-induced liver injury (DILI) with jaundice indicates a serious reaction, is used widely to determine risk for acute liver failure (ALF). We aimed to optimize the definition of Hy's Law and to develop a model for predicting ALF in patients with DILI. METHODS We collected data from 771 patients with DILI (805 episodes) from the Spanish DILI registry, from April 1994 through August 2012. We analyzed data collected at DILI recognition and at the time of peak levels of alanine aminotransferase (ALT) and total bilirubin (TBL). RESULTS Of the 771 patients with DILI, 32 developed ALF. Hepatocellular injury, female sex, high levels of TBL, and a high ratio of aspartate aminotransferase (AST):ALT were independent risk factors for ALF. We compared 3 ways to use Hy's Law to predict which patients would develop ALF; all included TBL greater than 2-fold the upper limit of normal (×ULN) and either ALT level greater than 3 × ULN, a ratio (R) value (ALT × ULN/alkaline phosphatase × ULN) of 5 or greater, or a new ratio (nR) value (ALT or AST, whichever produced the highest ×ULN/ alkaline phosphatase × ULN value) of 5 or greater. At recognition of DILI, the R- and nR-based models identified patients who developed ALF with 67% and 63% specificity, respectively, whereas use of only ALT level identified them with 44% specificity. However, the level of ALT and the nR model each identified patients who developed ALF with 90% sensitivity, whereas the R criteria identified them with 83% sensitivity. An equal number of patients who did and did not develop ALF had alkaline phosphatase levels greater than 2 × ULN. An algorithm based on AST level greater than 17.3 × ULN, TBL greater than 6.6 × ULN, and AST:ALT greater than 1.5 identified patients who developed ALF with 82% specificity and 80% sensitivity. CONCLUSIONS When applied at DILI recognition, the nR criteria for Hy's Law provides the best balance of sensitivity and specificity whereas our new composite algorithm provides additional specificity in predicting the ultimate development of ALF. Yes
Published: 2014

48. Households or hotspots? Defining intervention targets for malaria elimination in Ratanakiri Province, eastern Cambodia

Author: Steven Abrams, Michael Boele van Hensbroek, Melanie Bannister-Tyrrell, Quique Bassat, Marc Coosemans, Sochantha Tho, Niel Hens, Vanna Mean, Saorin Kim, Mao Sokny, Meryam Krit, Koen Peeters Grietens, Vincent Sluydts, Wim Van Bortel, Lies Durnez, Didier Menard, Institute of Tropical Medicine [Antwerp] (ITM), University of Antwerp (UA), National Center for Parasitology, Entomology and Malaria Control [Phnom Penh, Cambodia] (CNM), Ratanakiri Provincial Health Department [Banlung, Cambodge], Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Hasselt University (UHasselt), Barcelona Institute for Global Health [Barcelona, Spain] (ISGlobal), Hospital Clinic [Barcelona, Spain]-University of Barcelona, Centro de Investigação em Saúde de Manhiça [Maputo, Mozambique] (CISM), Catalan Institution for Research and Advanced Studies, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Amsterdam Institute for Global Health & Development [Amsterdam, The Netherlands], General Paediatrics, Global Health, Paediatric Infectious Diseases / Rheumatology / Immunology, AII - Infectious diseases, and APH - Global Health
Subjects: Male, Plasmodium, Epidemiology, Logistic regression, Polymerase Chain Reaction, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Plasmodium Infections, Prevalence, Immunology and Allergy, Cluster Analysis, 030212 general & internal medicine, Child, malaria elimination, 2. Zero hunger, Family Characteristics, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, 1. No poverty, Middle Aged, 3. Good health, Infectious Diseases, Geography, Child, Preschool, Female, epidemiology, hotspot, Cambodia, Adult, medicine.medical_specialty, Adolescent, 030231 tropical medicine, malaria, Malària, Communicable Diseases, 03 medical and health sciences, Young Adult, Major Articles and Brief Reports, Environmental health, Malaria elimination, parasitic diseases, medicine, Humans, Greater Mekong Subregion, Malaria risk, Parasites, Epidemiologia, Biology, Cambodja, Spatial Analysis, Infant, Newborn, Infant, medicine.disease, Confidence interval, Malaria, Cross-Sectional Studies, Relative risk, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Human medicine
Abstract: Background Malaria “hotspots” have been proposed as potential intervention units for targeted malaria elimination. Little is known about hotspot formation and stability in settings outside sub-Saharan Africa. Methods Clustering of Plasmodium infections at the household and hotspot level was assessed over 2 years in 3 villages in eastern Cambodia. Social and spatial autocorrelation statistics were calculated to assess clustering of malaria risk, and logistic regression was used to assess the effect of living in a malaria hotspot compared to living in a malaria-positive household in the first year of the study on risk of malaria infection in the second year. Results The crude prevalence of Plasmodium infection was 8.4% in 2016 and 3.6% in 2017. Living in a hotspot in 2016 did not predict Plasmodium risk at the individual or household level in 2017 overall, but living in a Plasmodium-positive household in 2016 strongly predicted living in a Plasmodium-positive household in 2017 (Risk Ratio, 5.00 [95% confidence interval, 2.09–11.96], P < .0001). There was no consistent evidence that malaria risk clustered in groups of socially connected individuals from different households. Conclusions Malaria risk clustered more clearly in households than in hotspots over 2 years. Household-based strategies should be prioritized in malaria elimination programs in this region., In a low-transmission setting in eastern Cambodia, malaria risk clustered more clearly in households than in hotspots over 2 years. Household-based strategies should be prioritized in malaria elimination programs in this region.

49. Association between socioeconomic deprivation and colorectal cancer screening outcomes: low uptake rates among the most and least deprived people

Author: Andrea Buron, Josep M Auge, Maria Sala, Marta Román, Antoni Castells, Francesc Macià, Mercè Comas, Carolina Guiriguet, Xavier Bessa, Xavier Castells, and the PROCOLON research group, [Buron A, Sala M, Román M, Macià F, Comas M, Castells X] Departament d’Epidemiologia i Avaluació, Hospital del Mar, Barcelona, Spain. Institut Hospital de Mar d’Investigacions Mèdiques (IMIM), Barcelona, Spain. REDISSEC (Health Services Research on Chronic Patients Network), Madrid, Spain. [Auge JM] Servei de Bioquímica i Genètica Molecular, Hospital Clinic, Barcelona, Spain. IDIBAPS (Institut d’Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain. [Castells A] IDIBAPS (Institut d’Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain. Departament de Gastroenterologia, Hospital Clínic, Barcelona, Spain. Universitat de Barcelona, Spain. CIBERehd (CIBER for Digestive and Liver Diseases), Madrid, Spain. [Guiriguet C] Centre d’Atenció Primària (CAP) Gòtic, Institut Català de la Salut, Barcelona, Spain. Institut Universitari d'Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol), Barcelona, Spain. [Bessa X] Departament de Gastroenterologia, Hospital del Mar, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Cerdanyola del Vallès, Spain, and IDIAP Jordi Gol
Subjects: Colorectal cancer, lcsh:Medicine, Colonoscopy, Còlon -- Càncer -- Prevenció, Logistic regression, Geographical Locations, 0302 clinical medicine, Còlon - Càncer, Cancer screening, Medicine and Health Sciences, Cribatge (Medicina), Mass Screening, Public and Occupational Health, 030212 general & internal medicine, lcsh:Science, education.field_of_study, Multidisciplinary, medicine.diagnostic_test, neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias intestinales::neoplasias colorrectales [ENFERMEDADES], Mortality rate, Middle Aged, Socioeconomic Aspects of Health, Europe, Oncology, Research Design, 030220 oncology & carcinogenesis, Colorectal Neoplasms, Cancer Screening, Research Article, Neoplasias::Neoplasias por Localización::Neoplasias del Sistema Digestivo::Neoplasias Gastrointestinales::Neoplasias Intestinales::Neoplasias Colorrectales [ENFERMEDADES], Census, medicine.medical_specialty, Death Rates, Population, Investigative Techniques::Epidemiologic Methods::Data Collection::Surveys and Questionnaires::Health Surveys::Mass Screening [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES AND EQUIPMENT], ciencias sociales::sociología::factores sociológicos::factores socioeconómicos [ANTROPOLOGÍA, EDUCACIÓN, SOCIOLOGÍA Y FENÓMENOS SOCIALES], Surgical and Invasive Medical Procedures, Research and Analysis Methods, Diagnóstico::Técnicas y Procedimientos Diagnósticos::Tamizaje Masivo [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Digestive System Procedures, 03 medical and health sciences, Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [DISEASES], Diagnostic Medicine, Pacients - Condicions econòmiques, Social Sciences::Sociology::Sociological Factors::Socioeconomic Factors [ANTHROPOLOGY, EDUCATION, SOCIOLOGY AND SOCIAL PHENOMENA], Cancer Detection and Diagnosis, medicine, Humans, education, Mass screening, Aged, Retrospective Studies, Demography, Colorectal Cancer, Gynecology, Survey Research, diagnóstico::técnicas y procedimientos diagnósticos::cribado sistemático [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], business.industry, lcsh:R, Cancers and Neoplasms, Retrospective cohort study, medicine.disease, Health Care, Socioeconomic Factors, Spain, People and Places, lcsh:Q, business
Abstract: Càncer colorectal; Cribratge; Factors socioeconòmics Neoplasias colorrectales; Cribado; Factores socioeconómicos Colorectal Neoplasms; Screening; Socioeconomic Factors BACKGROUND Screening with faecal occult blood tests reduces colorectal cancer-related mortality; however, age, sex and socioeconomic factors affect screening outcomes and could lead to unequal mortality benefits. The aim of this study was to describe the main outcomes of the population-based Barcelona colorectal cancer screening programme (BCRCSP) by deprivation. METHODS: Retrospective study of the eligible population of the first round of the BCRCSP. Participants' postal addresses were linked with the MEDEA database to obtain the deprivation quintiles (Dq). Chi-squared tests were used to compare proportions across variables and logistic regression was used to estimate the adjusted effects of age, sex and deprivation on uptake, FIT positivity, colonoscopy adherence and advanced neoplasia detection rate. RESULTS: Overall uptake was 44.7%, higher in Dq2, 3 and 4 (OR 1.251, 1.250 and 1.276, respectively) than in the least deprived quintile (Dq 1), and lowest in Dq5 (OR 0.84). Faecal immunochemical test (FIT) positivity and the percentage of people with detectable faecal haemoglobin below the positivity threshold increased with deprivation. The advanced neoplasia detection rate was highest in Dq4. CONCLUSION: Unlike most regions where inequalities are graded along the socioeconomic continuum, inequalities in the uptake of colorectal cancer screening in Spain seem to be concentrated first in the most disadvantaged group and second in the least deprived group. The correlation of deprivation with FIT-positivity and faecal haemoglobin below the positivity threshold is worrying due to its association with colorectal cancer and overall mortality.

50. Refining Diagnostic Subtypes of Peripheral T-cell Lymphoma Using a Multiparameter Approach.

Author: Amador C, Weisenburger DD, Gomez A, Bouska A, Alshomrani A, Sharma S, Shah R, Greiner TC, Vega F, Rosenwald A, Ott G, Feldman AL, Jaffe ES, Ozkaya N, Ondrejka SL, Cook JR, Raess PW, Savage KJ, Slack GW, Song JY, Scott DW, Campo E, Rimsza LM, Khoury JD, Staudt LM, Chan WC, and Iqbal J
Abstract: Peripheral T-cell lymphoma (PTCL) is a heterogeneous category, and many cases are unclassifiable and designated as PTCL-not otherwise specified (PTCL-NOS). Gene expression profiling (GEP) has delineated two prognostic subtypes within PTCL-NOS, PTCL-TBX21, and PTCL-GATA3, characterized by distinctive transcriptomes and a different prognosis. To further evaluate the pathologic features of these subgroups, 101 PTCL cases that did not meet specific criteria for well-defined T-cell lymphoma entities underwent detailed pathologic, immunophenotypic (including T FH biomarkers) and GEP analyses, separating them into PTCL-NOS (n=63) and PTCL-TFH (a.k.a. nodal PTCL-TFH, NOS, and TFH lymphoma, NOS) (n=38). PTCL-NOS cases were further categorized into PTCL-GATA3 (n=22; 34%) and PTCL-TBX21 (n=41; 66%), and a significant association (p < 0.02) with overall survival (OS) was reaffirmed. Histopathological assessment showed PTCL-GATA3 cases were characterized by monotonous medium-sized or large transformed cells with a minimal tumor microenvironment (TME) compared to PTCL-TBX21 cases, which consisted of pleomorphic cells in a polymorphous TME (p < 0.05). GEP analysis validated these TME distinctions. Immunophenotypic analysis showed that PTCL-GATA3 cases were predominantly CD4+CD8- and associated with significantly higher LEF1, MYC, and CD30 expression (p < 0.05). PTCL-TBX21 displayed a more diverse biomarker profile with two subgroups: one expressing cytotoxic antigens and enriched in CD8+CD4- or CD8-CD4- phenotype, and another lacking cytotoxic markers but showing a CD4+CD8- phenotype with increased ICOS expression, but devoid of other T FH markers. The PTCL-TFH cases correlated with an angioimmunoblastic T-cell lymphoma (AITL) gene signature, had more EBER-positive cells than the PTCL-GATA3 and PTCL-TBX21 cases, and a subset had some morphologic features of AITL (p < 0.01). This study highlights the unique morphologic and phenotypic variations within the newly-identified PTCL subtypes and should enable more precise diagnosis and tailored therapeutic strategies in the future., (Copyright © 2024. Published by Elsevier Inc.)
Published: 2024
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