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1. 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
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2. 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
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3. 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
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4. 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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5. 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

6. A home enteral nutrition (HEN); spanish registry of NADYA-SENPE group; for the year 2013

Author

Wanden-Berghe, Carmina, Álvarez Hernández, Julia, Burgos Peláez, Rosa, Cuerda Compes, Cristina, Matía Martín, Pilar, Luengo Pérez, Luis Miguel, Gómez Candela, Carmen, Pérez de la Cruz, Antonio, Calleja Fernández, Alicia, Martínez Olmos, Miguel Ángel, Laborda González, Lucía, Campos Martín, Cristina, Leyes García, Pere, Irles Rocamora, José Antonio, Suárez Llanos, José Pablo, Cardona Pera, Daniel, Gonzalo Marín, Monserrat, Penacho Lázaro, María Ángeles, Ballesta Sáncez, Carmen, Rabasa Soler, Antoni, Garde Orbaiz, Carmen, Cánovas Gaillemin, Bárbara, Moreno Villares, José Manuel, del Olmo García, María Dolores, Carabaña Pérez, Fátima, Arraiza Irigoyen, Carmen, Mauri, Silvia, Sánchez-Vilar Burdiel, Olga, Virgili Casas, Nuria, Miserachs Aranda, Nuria, Apezetxea Celaya, Antxón, Pereira Soto, Manuel Ángel, Ponce González, Miguel Ángel, Grupo NADYA-SENPE, and [Wanden-Berghe,C]Hospital General Universitario de Alicante. Universidad Miguel Hernández. [Álvarez Hernández,J] Hospital Príncipe de Asturias, Alcalá de Henares, Madrid. [Burgos Peláez,R] Hospital Vall d’Hebrón, Barcelona. [Cuerda Compes,C] Hospital Gregorio Marañón, Madrid. [Matía Martín,C] Hospital Clínico San Carlos, Madrid. [Luengo Pérez,LM] Hospital Infanta Cristina, Badajoz. [Gómez Candela,C] Hospital La Paz, Madrid. [Pérez de la Cruz,A] Hospital Virgen de las Nieves, Granada. [Calleja Fernández,A] Complejo Asistencial de León. [Martínez Olmos,MA] Hospital de Conxo-CHUS, Santiago de Compostela. [Laborda González,L] Hospital de Cruces, Bilbao. [Campos Martín,C] Hospital Universitario Virgen Macarena, Sevilla. [Leyes García,P] Hospital Clinic, Barcelona. [Irles Rocamora,JA] Hospital Universitario Ntra. Sra. de Valme, Sevilla. [Suárez Llanos,JP] Hospital Universitario Nuestra Señora de la Candelaria, Santa Cruz de Tenerife. [Cardona Pera1,D] Hospital de la Santa Creu i Sant Pau, Barcelona. [Gonzalo Marín,M] Hospital Universitario Carlos Haya, Málaga. [Penacho Lázaro,MA] Hospital El Bierzo, Ponferrada, León. [Ballesta Sáncez,C] Hospital Sant Joan, Sant Joan de Alicante. [Rabassa Soler,A] Hospital Universitari Sant Joan de Reus, Tarragona. [Garde Orbaiz,C] Hospital Universitario Donostia, Guipuzkoa. [Cánovas Gaillemin,B] Hospital Virgen de la Salud, Toledo. [Moreno Villares,JM] Hospital Universitario 12 de Octubre, Madrid. [del Olmo García,MC] Hospital Universitario Severo Ochoa, Leganés, Madrid. [Carabaña Pérez,F] Hospital Ramón y Cajal, Madrid. [Arraiza Irigoyen,C] Complejo Hospitalario de Jaén. [Mauri,S] Hospital Josep Trueta, Girona. [Sánchez-Vilar Burdiel,O] Fundación Jiménez Díaz, Madrid. [Virgili Casas,N] Hospital Universitario Bellvitge, L’Hospitalet de Llobregat, Barcelona. [Miserachs Aranda,N] Hospital Fundació Esperit Sant (Santa Coloma de Gramanet), Barcelona. [Apezetxea Celaya,A] Hospital Basurto, Bilbao. [Pereira Soto,MA] Hospital Clínico Universitario Santiago de Compostela. [Ponce González,MA] Hospital Universitario Dr. Negrín, Gran Canaria, Spain.

Subjects
Adult, Male, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Feeding Methods::Enteral Nutrition [Medical Subject Headings], Adolescent, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Patient Care::Withholding Treatment [Medical Subject Headings], Check Tags::Male [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Digestive System Surgical Procedures::Gastrostomy [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Young Adult, Named Groups::Persons::Age Groups::Adult [Medical Subject Headings], Organisms::Eukaryota::Animals [Medical Subject Headings], Registros, Humans, Registries, Nutritional support, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Morbidity::Prevalence [Medical Subject Headings], Child, Named Groups::Persons::Age Groups::Child [Medical Subject Headings], Aged, Health Care::Health Care Facilities, Manpower, and Services::Health Facilities::Hospitals [Medical Subject Headings], Aged, 80 and over, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Birds::Galliformes::Chickens [Medical Subject Headings], Infant, Newborn, Infant, Middle Aged, Home care services, Home Care Services, Soporte nutricional, Check Tags::Female [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Intubation::Intubation, Gastrointestinal [Medical Subject Headings], Spain, Child, Preschool, Nutrición enteral, Cuidados domiciliarios, Female, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Registries [Medical Subject Headings], Enteral nutrition, Parenteral Nutrition, Home
Abstract

AIM: To present the results of the Spanish home enteral nutrition (HEN) registry of the NADYA-SENPE group for the year 2013. MATERIAL AND METHODS: From January 1st to December 31st 2013 data was recorded for the HEN registry and further descriptive and analytical analysis was done. RESULTS: In this period 3 223 patients (50.6% men) and a total of 3 272 episodes of HEN were registered in 33 Spanish hospitals. The rate of prevalence was of 67,11 patients/million habitants/ year 2013. A high percentage of patients (98,24%) were older than 14 years. Adult's mean age was 69,14 years (sd 17,64) and men were younger than women p-value

Published
2015

7. A Home and Ambulatory Artificial Nutrition (NADYA) group report, Home Parenteral Nutrition in Spain, 2013

Author

Wanden-Berghe, Carmina, Cuerda Compes, J Cristina, Burgos Peláez, Rosa, Gómez Candela, Carmen, Virgili Casas, Nuria, Pérez de la Cruz, Antonio, Moreno Villares, José Manuel, Carabaña Pérez, Fátima, Garde Orbaiz, Carmen, Martínez Faedo, Ceferino, Penacho Lázaro, Ma Ángeles, Gonzalo Marín, Montserrat, García Luna, Pedro Pablo, Matía Martín, Pilar, Sanz Paris, Alejandro, Luengo Pérez, Luis Miguel, Martín Folgueras, Tomás, García Zafra, María Victoria, Álvarez Hernández, Campos Martín, Cristina, Suárez Llanos, José Pablo, Zugasti, Ana, Apezetxea Celaya, Antxón, Urgeles Planella, Juan Ramon, Laborda González, Lucía, Sánchez-Vilar Burdiel, Olga, Joaquín Ortiz, Clara, Martínez Costa, Cecilia, Vidal Casariego, Alfonso, Leyes García, Pere, Ponce González, Miguel Angel, Gil Martínez, Ma Carmen, Sánchez Martos, Eva Ángeles, del Olmo García, Ma Dolores, Díaz Guardiola, Patricia, Grupo NADYA-SENPE, and [Wanden-Berghe,C] FISABIO-Hospital General Universitario de Alicante. Universidad Miguel Hernández (Elche), Alicante. [Cuerda Compes,JC] Hospital Gregorio Marañón. [Burgos Peláez,R] Hospital Vall d’Hebrón, Barcelona. [Gómez Candela,C] Hospital La Paz. [Virgili Casas,N] Hospital Universitario Bellvitge, L’Hospitalet de Llobregat, Barcelona. [Pérez de la Cruz,A] Hospital Virgen de las Nieves, Granada. [Moreno Villares,JM] Hospital Universitario 12 de Octubre, Madrid. [Carabaña Pérez,F] Hospital Ramón y Cajal, Madrid. [Garde Orbaiz,C] Hospital Universitario Donostia, Guipuzkoa. [Martínez Faedo,C] Hospital Universitario Central de Asturias. [Penacho Lázaro,MA] Hospital El Bierzo, Ponferrada, León. [Gonzalo Marín,M] Hospital Universitario Carlos Haya. Málaga. [García Luna,PP] Hospital Universitario Virgen del Rocío, Sevilla. [Matía Martín,P] Hospital Clínico San Carlos, Madrid. [Sanz Paris,A] Hospital Universitario Miguel Servet, Zaragoza. [Luengo Pérez,LM] Hospital Infanta Cristina, Badajoz. [Martín Folgueras,T] Complejo Hospitalario Universitario de Canarias, Santa Cruz de Tenerife. [García Zafra,MV] Hospital Universitario Virgen de la Arrixaca, Murcia. [Álvarez Hernández] Hospital Príncipe de Asturias ,Alcalá de Henares, Madrid. [Campos Martín,C] Hospital Universitario Virgen Macarena, Sevilla. [Suárez Llanos,JP] Hospital Universitario Nuestra Señora de la Candelaria, Santa Cruz de Tenerife. [Zugasti,A] Hospital Virgen del Camino, Pamplona. [Apezetxea Celaya,A] Hospital Basurto, Bilbao. [Urgeles Planella,JR] Hospital Universitario Son Espases, Palma de Mallorca. [Laborda González,L] Hospital de Cruce, Bilbao. [Sánchez-Vilar Burdiel,O] Fundación Jiménez Díaz, Madrid. [Joaquín Ortiz,C] Hospital Germans Trias i Pujol, Barcelona. [Martínez Costa,C] Hospital Clínico Universitario, Valencia. [Vidal Casariego,A] Complejo Asistencial de León. [Leyes García,P] Hospital Clinic, Barcelona. [Ponce González,MA] Hospital Universitario Dr Negrín, Gran Canaria. [Gil Martínez,MC] Hospital Central de la Defensa Gomez Ulla, Madrid. [Sánchez Martos,EA ] Corporació Sanitària Parc Taulí, Barcelona. [del Olmo García,MD] Hospital Universitario Severo Ochoa , Leganés, Madrid. [Díaz Guardiola,P] Hospital Infanta Sofía, San Sebastian de los Reyes, Madrid. Spain.

Subjects
Adult, Male, Adolescent, Nutrición parenteral domiciliaria, Nutrición parenteral, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Feeding Methods::Parenteral Nutrition::Parenteral Nutrition, Home [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Young Adult, Epidemiolgy, 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], Named Groups::Persons::Age Groups::Adult [Medical Subject Headings], Ambulatory Care, Registros, Epidemiología, Humans, Registries, Nutritional support, Child, Named Groups::Persons::Age Groups::Child [Medical Subject Headings], Diseases::Digestive System Diseases::Gastrointestinal Diseases::Intestinal Diseases [Medical Subject Headings], Aged, Aged, 80 and over, Home parenteral nutrition, Disciplines and Occupations::Social Sciences::Sociology::Minority Groups [Medical Subject Headings], Age Factors, Infant, Home care services, Diseases::Neoplasms [Medical Subject Headings], Middle Aged, Parenteral nutrition, Soporte nutricional, Diseases::Digestive System Diseases::Gastrointestinal Diseases::Intestinal Diseases::Intestinal Obstruction [Medical Subject Headings], Spain, Child, Preschool, Cuidados domiciliarios, Diseases::Digestive System Diseases::Gastrointestinal Diseases::Intestinal Diseases::Mesenteric Ischemia [Medical Subject Headings], Female, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Registries [Medical Subject Headings], Diseases::Digestive System Diseases::Gastrointestinal Diseases::Intestinal Diseases::Malabsorption Syndromes::Short Bowel Syndrome [Medical Subject Headings], Parenteral Nutrition, Home
Abstract

AIM: To communicate the results of the Spanish Home Parenteral Nutrition (HPN) registry of the NADYA-SENPE group for the year 2013. MATERIAL AND METHODS: Data was recorded online by NADYA group collaborators that were responsible of the HPN follow-up from 1st January to 31st December 2013. RESULTS: A total of 197 patients and 202 episodes of HPN were registered from 35 hospitals that represents a rate of 4,22 patients/million habitants/year 2013. The median age was 53 years (IQR 40-64) for 189 adult patients and 7 months (IQR 6-35,5) for children. The most frequent disease in adults was neoplasm (30,7%) followed by other diseases (20,1%) and mesenteric ischemia (12,7%). Short bowel syndrome and intestinal obstruction (25,9%) were in 35.7% cases the indications for HPN. The most frequent diagnosis for children were the congenital intestinal disorders and other diagnosis, both with a (37,5%) and short bowel syndrome and intestinal obstruction were the indication for treatment, each was present in 50% of the sample. Tunneled catheters (50%) and subcutaneous reservoirs (27,7%) were frequently used. The septic complications related with catheter were commonly frequent with a rate of 0.74 infections/1000 HPN days. HPN duration presented a median of 1,69 days. A total of 86 episodes finalized during the year, death was the principal reason (45%), followed by "resumed oral via" (43,75%) while it happened inversely for children, 66,7% of them resumed oral via and 16,7% deceased. Fifteen per cent were considered for intestinal transplant, children were proportionally candidates, p-value 0.002. CONCLUSIONS: The number of participating centers and registered patients increased progressively respect to preceding years. Since 2003 Neoplasm is still being the principal pathological group. Death is adult's principal reason for finalizing HPN and "resuming oral via" for children. Despite that NADYA registry is consolidate as a essential source of relevant information about the advances in Home Artificial Nutrition in our country, currently is in an improvement process of the available information about patients characteristics with a special emphasis on children even though they still being a minority group. Yes Objetivo: comunicar los datos del registro de Nutrición Parenteral Domiciliaria (NPD) del grupo de trabajo NADYA-SENPE del años 2013. Material y métodos: recopilación de los datos del registro “on-line” introducidos por los colaboradores del grupo NADYA responsables del seguimiento de la NPD desde el 1 de enero de 2013 al 31 de diciembre de 2013. Resultados: se registraron 197 pacientes, procedentes de 35 hospitales, lo que representa una tasa de 4,22 pacientes/ millón habitantes/año 2013, con 202 episodios de NPD. La edad media de los 189 pacientes mayores de 14 años fue de 53 años (IIQ 40 – 64), y en los niños de 7 meses (IIQ 6 – 35,5). La patología más frecuente en los adultos fue la neoplasia (30,7%) seguida por otras patologías (20,1%) y la isquemia mesentérica (12,7%). En el 35,4% de los casos el motivo de indicación fue el síndrome de intestino corto, seguido de la obstrucción intestinal (25,9%). En los niños el diagnóstico más frecuente fueron las alteraciones congénitas intestinales y ‘otros diagnósticos’, ambas con un 37,5 %, y la causa de la indicación el síndrome de intestino corto y la obstrucción intestinal, que se repartieron el 50% de la muestra. Los catéteres más utilizados fueron los tunelizados (50%) y los reservorios subcutáneos (27,7%). Las complicaciones más frecuentes fueron las sépticas, relacionadas con el catéter, con una tasa de 0,74 infecciones/1.000 días de NPD. La duración de la NPD presentó una mediana de 1,69 años. Durante el año finalizaron 86 episodios, la principal causa de la finalización en adultos fue el fallecimiento (45%) seguido del ‘paso a la vía oral’ (43,75%) y en los niños a la inversa 66,7% pasan a vía oral y 16,7% fallecen. Se consideraron candidatos para trasplante intestinal el 15% de los pacientes, siendo proporcionalmente los candidatos niños, p-valor 0,002. Conclusiones: se observa un aumento progresivo de los centros participantes y de los pacientes registrados respecto a años anteriores. El principal grupo patológico sigue siendo oncológico, ocupando el primer lugar desde 2003. La principal causa de finalización de la NPD es en los adultos el fallecimiento y en los niños el ‘paso a vía oral’. Aunque el registro NADYA es un registro consolidado y ha sido y es fuente imprescindible de información relevante para el conocimiento de los avances de la Nutrición Artificial Domiciliaria en nuestro país, se encuentra en proceso de mejorar la información que ofrece sobre las características de los pacientes, con especial atención en el grupo de niños, aunque estos siguen siendo un número reducido.

Published
2015

8. 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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9. Secondary autoimmune diseases occurring after HSCT for an autoimmune disease: a retrospective study of the EBMT Autoimmune Disease Working Party

Author

Daikeler, T., Labopin, M., Gioia, M. di, Abinun, M., Alexander, T., Miniati, I., Gualandi, F., Fassas, A., Martin, T., Schwarze, C.P., Wulffraat, N., Buch, M., Sampol, A., Carreras, E., Dubois, B., Gruhn, B., Gungor, T., Pohlreich, D., Schuerwegh, A., Snarski, E., Snowden, J., Veys, P., Fasth, A., Lenhoff, S., Messina, C., Voswinkel, J., Badoglio, M., Henes, J., Launay, D., Tyndall, A., Gluckman, E., Farge, D., EBMT Autoimmune Disease Working, Department of Rheumatology, University Hospital Basel [Basel], Service d'hématologie clinique et de thérapie cellulaire [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), Haematology Department, Careggi University Hospital, Newcastle General Hospital, Department of Rheumatology & Clinical Immunology, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Biomedicine, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Department of Haematology II, Ospedale San Martino, Neurology & Haematology, George Papanicolau Hospital, Immunologie et chimie thérapeutiques (ICT), Cancéropôle du Grand Est-Centre National de la Recherche Scientifique (CNRS), Paediatric Haematology & Endocrinology, University Children's Hospital, University Medical Center, VU University Medical Center [Amsterdam], Section of Musculoskeletal Disease, University of Leeds, Hospital Universitari Son Espases, Department of Hematology, Hospital Clinic Barcelona, Department of Neurology, University Hospitals Leuven [Leuven], Department of Pediatrics, Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], Division of Immunology/Hematology/BMT, Charles University Hospital, Leiden University Medical Center (LUMC), Department of Hematology & Oncology, Medical University of Warsaw - Poland, Department of Haematology & Department of Oncology, NHS & University of Sheffield, Great Ormond Street Hospital for Children [London] (GOSH), University of Gothenburg (GU), University Hospital Lund, Dipartimento di Pediatria, Cinica di Oncoematologia Pediatrica, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Hematology & Rheumatology, University Hospital Tübingen, Department of Internal Medicine, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Clinical Research Unit, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie, dermatologie, oncologie, Oncodermatologie, immunologie et cellules souches cutanées (IDO (U976 / UMR_S 976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), EULAR Grant & Freiwillige Akademische Gesellschaft Basel, Università degli Studi di Firenze = University of Florence (UniFI), Universiteit Leiden-Universiteit Leiden, University of Sheffield [Sheffield], and Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, stem-cell transplantation bone-marrow-transplantation hemolytic-anemia blood, medicine.medical_treatment, Hematopoietic stem cell transplantation, Biochemistry, Autoimmune thrombocytopenia, Antibodies, Monoclonal, Murine-Derived, 0302 clinical medicine, Prednisone, immune system diseases, Risk Factors, hemic and lymphatic diseases, Child, Hematopoietic Stem Cell Transplantation, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, 3. Good health, Europe, surgical procedures, operative, Treatment Outcome, 030220 oncology & carcinogenesis, Child, Preschool, Rituximab, Female, Autoimmune hemolytic anemia, Immunosuppressive Agents, medicine.drug, Adult, medicine.medical_specialty, Adolescent, Immunology, Autoimmune Diseases, 03 medical and health sciences, Young Adult, Antiphospholipid syndrome, Internal medicine, medicine, Humans, Immunologic Factors, Cyclophosphamide, Glucocorticoids, Retrospective Studies, Autoimmune disease, Lupus erythematosus, business.industry, Infant, Cell Biology, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, medicine.disease, Multivariate Analysis, business, 030215 immunology
Abstract

To specify the incidence and risk factors for secondary autoimmune diseases (ADs) after HSCT for a primary AD, we retrospectively analyzed AD patients treated by HSCT reported to EBMT from 1995 to 2009 with at least 1 secondary AD (cases) and those without (controls). After autologous HSCT, 29 of 347 patients developed at least 1 secondary AD within 21.9 (0.6-49) months and after allogeneic HSCT, 3 of 16 patients. The observed secondary ADs included: autoimmune hemolytic anemia (n = 3), acquired hemophilia (n = 3), autoimmune thrombocytopenia (n = 3), antiphospholipid syndrome (n = 2), thyroiditis (n = 12), blocking thyroid-stimulating hormone receptor antibody (n = 1), Graves disease (n = 2), myasthenia gravis (n = 1), rheumatoid arthritis (n = 2), sarcoidosis (n = 2), vasculitis (n = 1), psoriasis (n = 1), and psoriatic arthritis (n = 1). After autologous HSCT for primary AD, the cumulative incidence of secondary AD was 9.8% ± 2% at 5 years. Lupus erythematosus as primary AD, and antithymocyte globulin use plus CD34+ graft selection were important risk factors for secondary AD by multivariate analysis. With a median follow-up of 6.2 (0.54-11) years after autologous HSCT, 26 of 29 patients with secondary AD were alive, 2 died during their secondary AD (antiphospholipid syndrome, hemophilia), and 1 death was HSCT-related. This European multicenter study underlines the need for careful management and follow-up for secondary AD after HSCT.

Published
2011
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10. Use of Advanced Magnetic Resonance Imaging Techniques in Neuromyelitis Optica Spectrum Disorder

Author

Ho Jin Kim, Sven Schippling, Eric C. Klawiter, Kerstin Hellwig, Félix Renard, Koon-Ho Chan, Ichiro Nakashima, Kazuo Fujihara, Lekha Pandit, Daniëlle E van Pelt, Jérôme De Seze, Naraporn Prayoonwiwat, Albert Saiz, Stéphane Kremer, Jeffrey Bennett, Metha Apiwattanakul, Jens Wuerfel, Douglas Kazutoshi Sato, Friedemann Paul, Terry J. Smith, Olaf Stüve, Marco Aurélio Lana-Peixoto, Nasrin Asgari, Simon Broadley, Maria Isabel Leite, Philippe Cabre, Brenda Banwell, May H. Han, Ingo Kleiter, Emmanuelle Waubant, Sophie Achard, Thomas F. Tedder, Kevin C. O’Connor, Silvia Tenembaum, Romain Marignier, Pablo Villoslada, Katja Van Herle, Scott S. Zamvil, Gareth R. John, Tanuja Chitnis, Anu Jacob, D. Craig Hooper, Jacqueline Palace, Orhan Aktas, Michael J. Levy, Benjamin Greenberg, Dean M. Wingerchuk, Michael R. Yeaman, Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Les Hôpitaux Universitaires de Strasbourg (HUS), GIPSA - Communication Information and Complex Systems (GIPSA-CICS), Département Images et Signal (GIPSA-DIS), Grenoble Images Parole Signal Automatique (GIPSA-lab), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Stendhal - Grenoble 3-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Stendhal - Grenoble 3-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Grenoble Images Parole Signal Automatique (GIPSA-lab), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Stendhal - Grenoble 3-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Stendhal - Grenoble 3-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS), Universidade Federal de Minas Gerais = Federal University of Minas Gerais [Belo Horizonte, Brazil] (UFMG), Oxford University Hospitals NHS Trust, University of Oxford, University of Southern Denmark (SDU), Vejle Hospital [Danemark], Harvard Medical School [Boston] (HMS), 'Juan Pedro Garrahan' National Hospital of Pediatrics, Buenos Aires, University of Pennsylvania, Children’s Hospital of Philadelphia (CHOP ), University of Texas Southwestern Medical Center [Dallas], University of Colorado [Denver], Johns Hopkins University (JHU), University of Barcelona, Hospital Clinic Barcelona, Tohoku University Graduate School of Medicine, The University of Hong Kong (HKU), University hospital of Zurich [Zurich], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Research Institute [Goyang], Hospital of National Cancer Center [Goyang], University Medical Center Göttingen (UMG), Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Stendhal - Grenoble 3-Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Stendhal - Grenoble 3-Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Grenoble Images Parole Signal Automatique (GIPSA-lab), Université Stendhal - Grenoble 3-Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Stendhal - Grenoble 3-Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS), University of Minas Gerais, University of Oxford [Oxford], Vejle Hospital, and University of Pennsylvania [Philadelphia]

Subjects
Diffusion Tensor Imaging/statistics & numerical data, Pathology, medicine.medical_specialty, BRAIN-LESION DISTRIBUTION VOXEL-BASED MORPHOMETRY APPEARING WHITE-MATTER MULTIPLE-SCLEROSIS COGNITIVE IMPAIRMENT MRI ABNORMALITIES FUNCTIONAL MRI DIFFUSION DAMAGE MS, Aucun, utilization, diagnosis, epidemiology, Neuromyelitis Optica/diagnosis, Article, Magnetic Resonance Imaging/statistics & numerical data, White matter, Nuclear magnetic resonance, Neuroimaging, medicine, Medical imaging, Humans, Spectrum disorder, ComputingMilieux_MISCELLANEOUS, Clinical Trials as Topic/methods, Clinical Trials as Topic, Neuromyelitis optica, medicine.diagnostic_test, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, Neuromyelitis Optica, Magnetic resonance imaging, medicine.disease, Magnetic Resonance Imaging, 3. Good health, [STAT]Statistics [stat], Diffusion Tensor Imaging, medicine.anatomical_structure, Neurology (clinical), business, Functional magnetic resonance imaging, Diffusion MRI
Abstract

Brain parenchymal lesions are frequently observed on conventional magnetic resonance imaging (MRI) scans of patients with neuromyelitis optica (NMO) spectrum disorder, but the specific morphological and temporal patterns distinguishing them unequivocally from lesions caused by other disorders have not been identified. This literature review summarizes the literature on advanced quantitative imaging measures reported for patients with NMO spectrum disorder, including proton MR spectroscopy, diffusion tensor imaging, magnetization transfer imaging, quantitative MR volumetry, and ultrahigh-field strength MRI. It was undertaken to consider the advanced MRI techniques used for patients with NMO by different specialists in the field. Although quantitative measures such as proton MR spectroscopy or magnetization transfer imaging have not reproducibly revealed diffuse brain injury, preliminary data from diffusion-weighted imaging and brain tissue volumetry indicate greater white matter than gray matter degradation. These findings could be confirmed by ultrahigh-field MRI. The use of nonconventional MRI techniques may further our understanding of the pathogenic processes in NMO spectrum disorders and may help us identify the distinct radiographic features corresponding to specific phenotypic manifestations of this disease. journal article review 2015 Jul imported

Published
2015
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11. 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
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