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34 results on '"Hospital Universitari i Politècnic La Fe"'

1. An ESPGHAN Position Paper on the Use of Breath Testing in Paediatric Gastroenterology

Author

Rut Ann Thomassen, Jernej Dolinsek, Carmen Ribes-Koninckx, Erasmo Miele, Christos Tzivinikos, Corina Pienar, Javier Martín-de-Carpi, Emmanuel Mas, Marc A. Benninga, Osvaldo Borrelli, Ilse Broekaert, Mike Thomson, University Hospital of Cologne [Cologne], Great Ormond Street Hospital for Children [London] (GOSH), University medical centre Maribor (UKC Maribor), Hospital Sant Joan de Déu [Barcelona], Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 'Federico II' University of Naples Medical School, Victor Babeş University of Medicine and Pharmacy (UMFT), Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, Oslo University Hospital [Oslo], Sheffield Children's NHS Foundation Trust, Al Jalila Children's Specialty Hospital, VU University Medical Center [Amsterdam], SEGUIN, Nathalie, Broekaert, Ilse Julia, Borrelli, Osvaldo, Dolinsek, Jernej, Martin-de-Carpi, Javier, Mas, Emmanuel, Miele, Erasmo, Pienar, Corina, Ribes-Koninckx, Carmen, Thomassen, Rut, Thomson, Mike, Tzivinikos, Christo, Benninga, Marc, and Hospital Universitari i Politècnic La Fe

Subjects
medicine.medical_specialty, Malabsorption, Consensus, Carbohydrate malabsorption, 030309 nutrition & dietetics, MEDLINE, carbohydrate malabsorption, small intestinal bacterial overgrowth, Helicobacter pylori infection, Helicobacter Infections, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, children, Internal medicine, Small intestinal bacterial overgrowth, medicine, breath testing, Humans, Intensive care medicine, Exocrine pancreatic insufficiency, Child, Children, 0303 health sciences, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hepatology, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, Fat malabsorption, Breath testing, Systematic review, Breath Tests, Pediatrics, Perinatology and Child Health, Position paper, 030211 gastroenterology & hepatology, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Systematic Reviews as Topic
Abstract

International audience; Objectives: Given a lack of a systematic approach to the use of breath testing in paediatric patients, the aim of this position paper is to provide expert guidance regarding the indications for its use and practical considerations to optimise its utility and safety. Methods: Nine clinical questions regarding methodology, interpretation, and specific indications of breath testing and treatment of carbohydrate malabsorption were addressed by members of the Gastroenterology Committee (GIC) of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN). A systematic literature search was performed from 1983 to 2020 using PubMed, the MEDLINE and Cochrane Database of Systematic Reviews. Grading of Recommendations, Assessment, Development, and Evaluation was applied to evaluate the outcomes. During a consensus meeting, all recommendations were discussed and finalised. In the absence of evidence from randomised controlled trials, recommendations reflect the expert opinion of the authors. Results: A total of 22 recommendations were voted on using the nominal voting technique. At first, recommendations on prerequisites and preparation for as well as on interpretation of breath tests are given. Then, recommendations on the usefulness of H2-lactose breath testing, H2-fructose breath testing as well as of breath tests for other types of carbohydrate malabsorption are provided. Furthermore, breath testing is recommended to diagnose small intestinal bacterial overgrowth (SIBO), to control for success of Helicobacter pylori eradication therapy and to diagnose and monitor therapy of exocrine pancreatic insufficiency, but not to estimate oro-caecal transit time (OCTT) or to diagnose and follow-up on celiac disease. Conclusions: Breath tests are frequently used in paediatric gastroenterology mainly assessing carbohydrate malabsorption, but also in the diagnosis of small intestinal overgrowth, fat malabsorption, H. pylori infection as well as for measuring gastrointestinal transit times. Interpretation of the results can be challenging and in addition, pertinent symptoms should be considered to evaluate clinical tolerance.

Published
2021

2. Deciphering Multiple Sclerosis Progression

Author

Virginia Meca-Lallana, Leticia Berenguer-Ruiz, Joan Carreres-Polo, Sara Eichau-Madueño, Jaime Ferrer-Lozano, Lucía Forero, Yolanda Higueras, Nieves Téllez Lara, Angela Vidal-Jordana, Francisco Carlos Pérez-Miralles, Institut Català de la Salut, [Meca-Lallana V] Multiple Sclerosis Unit, Neurology Department, Fundación de Investigación Biomédica, Hospital Universitario de la Princesa, Madrid, Spain. [Berenguer-Ruiz L] Neurology Department, Hospital Marina Baixa, Alicante, Spain. [Carreres-Polo J] Neuroradiology Section, Radiology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain. [Eichau-Madueño S] Multiple Sclerosis CSUR Unit, Neurology Department, Hospital Universitario Virgen Macarena, Seville, Spain. [Ferrer-Lozano J] Department of Pathology, Hospital Universitari i Politècnic La Fe, Valencia, Spain. [Forero L] Neurology Department, Hospital Puerta del Mar, Cádiz, Spain. [Vidal-Jordana A] Servei de Neurologia/Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya (CEMCAT), Barcelona, Spain. Vall d'Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Oncology, medicine.medical_specialty, Other subheadings::Other subheadings::/physiopathology [Other subheadings], Otros calificadores::Otros calificadores::/fisiopatología [Otros calificadores], Esclerosi múltiple - Propensió, Genetic Phenomena::Genotype::Genetic Predisposition to Disease [PHENOMENA AND PROCESSES], Review, Disease, neurofilament, Esclerosi múltiple - Fisiologia patològica, multiple sclerosis, lcsh:RC346-429, Sistema nerviós - Degeneració, 03 medical and health sciences, 0302 clinical medicine, Degenerative disease, Internal medicine, medicine, In patient, 030212 general & internal medicine, enfermedades del sistema nervioso::enfermedades neurodegenerativas [ENFERMEDADES], lcsh:Neurology. Diseases of the nervous system, fenómenos genéticos::genotipo::predisposición genética a la enfermedad [FENÓMENOS Y PROCESOS], Expanded Disability Status Scale, business.industry, Multiple sclerosis, Neurodegeneration, Disease progression, neurodegeneration, Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis [DISEASES], medicine.disease, Clinical trial, progressive multiple sclerosis, Neurology, Nervous System Diseases::Neurodegenerative Diseases [DISEASES], enfermedades del sistema nervioso::enfermedades autoinmunitarias del sistema nervioso::enfermedades autoinmunes desmielinizantes del SNC::esclerosis múltiple [ENFERMEDADES], Neurology (clinical), business, 030217 neurology & neurosurgery, MRI
Abstract

Esclerosi múltiple; Neurodegeneració Esclerosis múltiple; Neurodegeneración Multiple sclerosis; Nneurodegeneration Multiple sclerosis (MS) is primarily an inflammatory and degenerative disease of the central nervous system, triggered by unknown environmental factors in patients with predisposing genetic risk profiles. The prevention of neurological disability is one of the essential goals to be achieved in a patient with MS. However, the pathogenic mechanisms driving the progressive phase of the disease remain unknown. It was described that the pathophysiological mechanisms associated with disease progression are present from disease onset. In daily practice, there is a lack of clinical, radiological, or biological markers that favor an early detection of the disease's progression. Different definitions of disability progression were used in clinical trials. According to the most descriptive, progression was defined as a minimum increase in the Expanded Disability Status Scale (EDSS) of 1.5, 1.0, or 0.5 from a baseline level of 0, 1.0–5.0, and 5.5, respectively. Nevertheless, the EDSS is not the most sensitive scale to assess progression, and there is no consensus regarding any specific diagnostic criteria for disability progression. This review document discusses the current pathophysiological concepts associated with MS progression, the different measurement strategies, the biomarkers associated with disability progression, and the available pharmacologic therapeutic approaches.

Published
2021

3. Integrative and comparative genomic analyses identify clinically relevant pulmonary carcinoid groups and unveil the supra-carcinoids

Author

F. Le Calvez-Kelm, John K. Field, Nicolas Girard, Ernst-Jan M. Speel, Marie Brevet, Lynnette Fernandez-Cuesta, Jean-François Deleuze, Nicolas Lemaitre, Noémie Leblay, Sandrine Boyault, Marius Lund-Iversen, Gabriella Sozzi, Véronique Hofman, Sylvie Lantuejoul, Lucia Anna Muscarella, Paolo Graziano, Alex Soltermann, Matthieu Foll, Amelie Chabrier, Robert Olaso, A. Ferrari, Anne Boland, Paul Hofman, Luca Roz, Behnoush Abedi-Ardekani, Janine Altmüller, Tiffany M. Delhomme, Akram Ghantous, Christophe Caux, Jules L. Derks, Giuseppe Pelosi, Vincent Meyer, Anne-Marie C. Dingemans, Juan Sandoval, Jean-Michel Vignaud, Jelena Stojsic, Catherine Voegele, Geoffroy Durand, James D. McKay, Peter Nuernberg, Cyrille Cuenin, Nicolas Alcala, L. Moonen, Hector Hernandez-Vargas, Ugo Pastorino, Theo Giffon, O.T. Brustugun, L. Mangiante, Mauro Papotti, Philippe Lorimier, Anne-Claire Toffart, Prudence A. Russell, Aurélie A G Gabriel, Zdenko Herceg, A. S. Sertier, Joachim H. Clement, M. Milione, Joerg Saenger, Luka Brcic, Stéphanie Lacomme, V. Thomas de Montpreville, A. Viari, Marco Volante, Elisabeth Brambilla, Gavin M. Wright, Cécile Blanc-Fournier, David Hervás, N. Le Stang, H. Popper, Françoise Galateau-Sallé, Centre international de Recherche sur le Cancer (CIRC), Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, Fondation Synergie Lyon Cancer [Lyon], Centre Léon Bérard [Lyon], Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Cologne Center for Genomics [Cologne] (CCG), University of Cologne, Centre for Molecular Medicine Cologne [Cologne] (CMMC), University Hospital of Cologne [Cologne], School for Oncology and Developmental Biology [Maastricht] (GROW), Maastricht University [Maastricht]-Maastricht University Medical Centre (MUMC), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service de pneumologie [Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Institute of Pathology and Molecular Pathology [Zurich], Department Hematology and Medical Oncology [Jena], Jena University Hospital [Jena], Central Clinic Bad Berka, Department of Molecular and Clinical Cancer Medicine [Liverpool], University of Liverpool, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), University of Melbourne, IRCCS Istituto Nazionale dei Tumori [Milano], Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Oslo University Hospital [Oslo], Centre Chirurgical Marie Lannelongue (CCML), Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Casa Sollievo della Sofferenza [San Giovanni Rotondo] (IRCCS), University Hospital Graz, Clinical Center of Serbia (KCS), Equipe de recherche européenne en algorithmique et biologie formelle et expérimentale (ERABLE), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Università degli Studi di Milano = University of Milan (UNIMI), Università degli studi di Torino = University of Turin (UNITO), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), 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), Hospital Universitari i Politècnic La Fe, Synergie Lyon Cancer [Lyon], UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Université Nice Sophia Antipolis (... - 2019) (UNS), Centre chirurgical Marie Lannelongue, University of Milan, University of Turin, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Promovendi ODB, Pulmonologie, RS: GROW - R2 - Basic and Translational Cancer Biology, MUMC+: MA Med Staf Spec Longziekten (9), and Pathologie

Subjects
0301 basic medicine, Oncology, Male, Lung Neoplasms, [SDV]Life Sciences [q-bio], General Physics and Astronomy, Datasets as Topic, 02 engineering and technology, Neuroendocrine tumors, Machine Learning, PATHWAY, Cancer genomics, lcsh:Science, Lung, Aged, 80 and over, Comparative Genomic Hybridization, Multidisciplinary, Intracellular Signaling Peptides and Proteins, Genomics, Middle Aged, 021001 nanoscience & nanotechnology, Prognosis, 3. Good health, Neuroendocrine Carcinomas, Survival Rate, medicine.anatomical_structure, Female, Non small cell, HEALTH, Technology Platforms, 0210 nano-technology, Adult, EXPRESSION, medicine.medical_specialty, Adolescent, Science, CELL LUNG-CANCER, Nerve Tissue Proteins, Carcinoid Tumor, DENDRITIC CELLS, General Biochemistry, Genetics and Molecular Biology, Article, Small-cell lung cancer, CLASSIFICATION, 03 medical and health sciences, Young Adult, Internal medicine, Overall survival, medicine, Carcinoma, Biomarkers, Tumor, Humans, Survival rate, Aged, Homeodomain Proteins, IDENTIFICATION, business.industry, MUTATIONS, Membrane Proteins, General Chemistry, medicine.disease, Small Cell Lung Carcinoma, 030104 developmental biology, DISCOVERY, Carcinoma, Large Cell, lcsh:Q, business, NEUROENDOCRINE TUMORS, Comparative genomic hybridization
Abstract

The worldwide incidence of pulmonary carcinoids is increasing, but little is known about their molecular characteristics. Through machine learning and multi-omics factor analysis, we compare and contrast the genomic profiles of 116 pulmonary carcinoids (including 35 atypical), 75 large-cell neuroendocrine carcinomas (LCNEC), and 66 small-cell lung cancers. Here we report that the integrative analyses on 257 lung neuroendocrine neoplasms stratify atypical carcinoids into two prognostic groups with a 10-year overall survival of 88% and 27%, respectively. We identify therapeutically relevant molecular groups of pulmonary carcinoids, suggesting DLL3 and the immune system as candidate therapeutic targets; we confirm the value of OTP expression levels for the prognosis and diagnosis of these diseases, and we unveil the group of supra-carcinoids. This group comprises samples with carcinoid-like morphology yet the molecular and clinical features of the deadly LCNEC, further supporting the previously proposed molecular link between the low- and high-grade lung neuroendocrine neoplasms., The worldwide incidence of pulmonary carcinoids is increasing, but little is known about their molecular characteristics. Here, Alcala and colleagues present a multi-omics analysis of these tumours, revealing distinct molecular and prognostic subgroups.

Published
2019

4. J Acquir Immune Defic Syndr

Author

Daniel Gillor, Lars P. Ryder, Rodolphe Thiébaut, Luuk Gras, Santiago Moreno, Marie Helleberg, Peter Reiss, Michael S. Saag, Margaret T May, Jonathan A C Sterne, Ferdinand W. N. M. Wit, Janet Tate, Niels Obel, Frank de Wolf, Ronald B. Geskus, Colette Smith, José M. Miró, Jodie L. Guest, Dominique Costagliola, Suzanne M Ingle, Matthias Cavassini, Antonella dʼArminio Monforte, Heidi M. Crane, Marta Montero, Timothy R. Sterling, Leah Shepherd, Viviane D. Lima, Christoph Stephan, Adam Trickey, Armin Rieger, John Gill, Antiretroviral Therapy Cohort Collaboration (ART-CC), Stichting HIV Monitoring [Amsterdam], Universiteit van Amsterdam (UvA), University of Bristol [Bristol], University of Copenhagen = Københavns Universitet (KU), Rigshospitalet [Copenhagen], Copenhagen University Hospital, Statistics In System biology and Translational Medicine (SISTM), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)- Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Emory University School of Medicine, Emory University [Atlanta, GA], University of Calgary, University of Washington [Seattle], British Columbia Centre for Excellence in HIV/AIDS [Vancouver], University of British Columbia (UBC), University of Milan, Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), University of Barcelona, Hospital Universitario Ramón y Cajal [Madrid], Universidad de Alcalá - University of Alcalá (UAH), Universitätsklinikum Frankfurt, Goethe-University Frankfurt am Main, University College of London [London] (UCL), Yale University School of Medicine, University of Alabama at Birmingham [ Birmingham] (UAB), University of Vienna [Vienna], Universität zu Köln, Université de Lausanne (UNIL), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Hospital Universitari i Politècnic La Fe, University of Amsterdam [Amsterdam] (UvA), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU), Amsterdam Institute for Global Health & Development [Amsterdam, The Netherlands], Imperial College London, Public Health Service of Amsterdam, University of Oxford [Oxford], University of Copenhagen = Københavns Universitet (UCPH), Università degli Studi di Milano = University of Milan (UNIMI), Yale School of Medicine [New Haven, Connecticut] (YSM), Universität zu Köln = University of Cologne, Université de Lausanne = University of Lausanne (UNIL), Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), University of Oxford, Gestionnaire, Hal Sorbonne Université, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Université de Bordeaux (UB), Graduate School, AII - Infectious diseases, APH - Global Health, APH - Methodology, Global Health, and APH - Aging & Later Life

Subjects
CD8 ratio [CD4], Male, Oncology, Cross-sectional study, CD4:CD8 ratio, [SDV]Life Sciences [q-bio], Cell, Human immunodeficiency virus (HIV), CD4-CD8 Ratio, CD4 cell count, HIV Infections, CD8-Positive T-Lymphocytes, 030312 virology, medicine.disease_cause, MORPH3Eus, Pharmacology (medical), Longitudinal Studies, Young adult, Cd4 cell count, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Clinical Science, Middle Aged, Viral Load, SISTM, 3. Good health, Antiretroviral therapy, [SDV] Life Sciences [q-bio], Infectious Diseases, medicine.anatomical_structure, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Female, Coll_IDLIC, Adult, medicine.medical_specialty, Adolescent, Anti-HIV Agents, CD8 cell count, antiretroviral therapy, Young Adult, 03 medical and health sciences, Age, Internal medicine, medicine, Coll_ART-CC, Humans, Lymphocyte Count, Anti-HIV Agents/therapeutic use, CD4 Lymphocyte Count, Cross-Sectional Studies, HIV Infections/drug therapy, HIV-1, Viral Load/drug effects, business.industry, HIV, age, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, CD8, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Supplemental Digital Content is Available in the Text., Background: An increasing number of HIV-positive individuals now start antiretroviral therapy (ART) with high CD4 cell counts. We investigated whether this makes restoration of CD4 and CD8 cell counts and the CD4:CD8 ratio during virologically suppressive ART to median levels seen in HIV-uninfected individuals more likely and whether restoration depends on gender, age, and other individual characteristics. Methods: We determined median and quartile reference values for CD4 and CD8 cell counts and their ratio using cross-sectional data from 2309 HIV-negative individuals. We used longitudinal measurements of 60,997 HIV-positive individuals from the Antiretroviral Therapy Cohort Collaboration in linear mixed-effects models. Results: When baseline CD4 cell counts were higher, higher long-term CD4 cell counts and CD4:CD8 ratios were reached. Highest long-term CD4 cell counts were observed in middle-aged individuals. During the first 2 years, median CD8 cell counts converged toward median reference values. However, changes were small thereafter and long-term CD8 cell count levels were higher than median reference values. Median 8-year CD8 cell counts were higher when ART was started with

Published
2018

5. Single- or double-unit UCBT following RIC in adults with AL: a report from Eurocord, the ALWP and the CTIWP of the EBMT

Author

Annalisa Ruggeri, Jan J. Cornelissen, Eliane Gluckman, Patrice Chevallier, Mohamad Mohty, Bipin N. Savani, Guillermo Sanz, Frédéric Baron, Didier Blaise, Myriam Labopin, Eefke Petersen, Arnon Nagler, Eric Beohou, Department of Hematology [Liege, Belgium], CHU Sart Tilman [Liege, Belgium]-Université de Liège, Eurocord [AP-HP Hôpital Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7), 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), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hématologie [Marseille], Centre de Lutte contre le Cancer-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Service d'Hématologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Servicio de Hematologia [Valencia, Spain], Hospital Universitari i Politècnic La Fe, Department of Hematology [Utrecht, The Netherlands] (UMCU), University Medical Center [Utrecht], Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], France Monacord [Monaco], Centre Scientifique de Monaco (CSM), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), Division of Hematology and Bone Marrow Transplantation [Ramat-Gan, Israel], The Chaim Sheba Medical Center at Tel hashomer, no source, Université de Liège-CHU Sart Tilman [Liege, Belgium], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Centre de Lutte contre le Cancer, Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, BMC, BMC, and Hematology

Subjects
Oncology, Male, Cancer Research, Transplantation Conditioning, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Single, Graft vs Host Disease, Hematopoietic stem cell transplantation, 0302 clinical medicine, AML, Medicine, 10. No inequality, Reduced-intensity, Univariate analysis, Hematology, Incidence (epidemiology), Hematopoietic Stem Cell Transplantation, lcsh:Diseases of the blood and blood-forming organs, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Fetal Blood, 3. Good health, [SDV] Life Sciences [q-bio], Leukemia, Myeloid, Acute, Treatment Outcome, 030220 oncology & carcinogenesis, Female, Cord Blood Stem Cell Transplantation, Adult, medicine.medical_specialty, Adolescent, Double, lcsh:RC254-282, 03 medical and health sciences, Young Adult, Unrelated cord blood, Internal medicine, Humans, Molecular Biology, Aged, Retrospective Studies, Transplantation, Neutrophil Engraftment, business.industry, lcsh:RC633-647.5, Research, Retrospective cohort study, Surgery, UCB, Neoplasm Recurrence, Local, business, ALL, 030215 immunology
Abstract

Background The feasibility of cord blood transplantation (CBT) in adults is limited by the relatively low number of hematopoietic stem/progenitor cells contained in one single CB unit. The infusion of two CB units from different partially HLA-matched donors (double CBT) is frequently performed in patients who lack a sufficiently rich single CB unit. Methods We compared CBT outcomes in patients given single or double CBT following reduced-intensity conditioning (RIC) in a retrospective multicenter registry-based study. Inclusion criteria included adult (≥18 years) patients, acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL), complete remission (CR) at the time of transplantation, first single (with a cryopreserved TNC ≥ 2.5 × 107/kg) or double CBT between 2004 and 2014, and RIC conditioning. Results Data from 534 patients with AML (n = 408) or ALL (n = 126) receiving a first single (n = 172) or double (n = 362) CBT were included in the analyses. In univariate analysis, in comparison to patients transplanted with a single CB, double CB recipients had a similar incidence of neutrophil engraftment but a suggestion for a higher incidence of grade II–IV acute GVHD (36 versus 28%, P = 0.08). In multivariate analyses, in comparison to single CBT recipients, double CBT patients had a comparable incidence of relapse (HR = 0.9, P = 0.5) and of nonrelapse mortality (HR = 0.8, P = 0.3), as well as comparable overall (HR = 0.8, P = 0.17), leukemia-free (HR = 0.8, P = 0.2) and GVHD-free, relapse-free (HR = 1.0, P = 0.3) survival. Conclusions These data failed to demonstrate better transplantation outcomes in adult patients receiving double CBT in comparison to those receiving single CBT with adequate TNC after RIC. Electronic supplementary material The online version of this article (doi:10.1186/s13045-017-0497-9) contains supplementary material, which is available to authorized users.

Published
2017

6. Unrelated cord blood transplantation for adult patients with acute myeloid leukemia: higher incidence of acute graft-versus-host disease and lower survival in male patients transplanted with female unrelated cord blood--a report from Eurocord, the Acute Leukemia Working Party, and the Cord Blood Committee of the Cellular Therapy and Immunobiology Working Party of the European Group for Blood and Marrow Transplantation

Author

Baron, Frédéric, Labopin, Myriam, Ruggeri, Annalisa, Mohty, Mohamad, Sanz, Guillermo, Milpied, Noel, Bacigalupo, Andrea, Rambaldi, Alessandro, Bonifazi, Francesca, Bosi, Alberto, Sierra, Jorge, Yakoub-Agha, Ibrahim, Ribera, Jose-Maria, Gluckman, Eliane, Nagler, Arnon, Universitat Autònoma de Barcelona, Service d'Hématologie, Université de Liège-CHU Sart-Tilman, Centre International des greffes [CHU Saint-Antoine] (EBMT), 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), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Eurocord, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7), Servicio de Hematologia, Hospital Universitari i Politècnic La Fe, Service d'Hématologie et Thérapie Cellulaire, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Department of Haematology II, Ospedale San Martino, Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera Papa Giovanni XXIII, Institute of Hematology and Medical, Oncology L and A Seràgnoli, Policlinico S. Orsola - Malpighi, Bone Marrow Transplant Unit (BMT), Azienda Ospedaliera Careggi, Hematology Department, Hospital de la Santa Creu i Sant Pau, Unités d'Activité Médicale [Lille] (UAM), Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Jose Carreras Research Institute, Hospital Universitari Germans Trias i Pujol, France Monacord, Centre Scientifique de Monaco (CSM), Division of Hematology and Bone Marrow Transplantation, The Chaim Sheba Medical Center at Tel hashomer, Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, BMC, BMC, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut Universitaire d'Hématologie (IUH), and Hôpital Claude Huriez-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)

Subjects
Male, Cancer Research, [SDV]Life Sciences [q-bio], GVHD, Graft vs Host Disease, Blood Donors, 0302 clinical medicine, AML, Risk Factors, hemic and lymphatic diseases, Medicine, 0303 health sciences, Acute leukemia, Hematology, Incidence, Hazard ratio, Middle Aged, 3. Good health, Europe, Survival Rate, [SDV] Life Sciences [q-bio], Leukemia, surgical procedures, operative, Oncology, Leukemia, Myeloid, 030220 oncology & carcinogenesis, Cord blood, Acute Disease, Female, Cord Blood Stem Cell Transplantation, Adult, medicine.medical_specialty, Adolescent, 03 medical and health sciences, Young Adult, Sex Factors, Unrelated cord blood, Sang fetal, Internal medicine, Humans, Survival rate, Molecular Biology, 030304 developmental biology, Aged, Retrospective Studies, Transplantation, business.industry, Research, medicine.disease, Survival Analysis, Surgery, Multivariate Analysis, business
Abstract

Background In the setting of allogeneic human leukocyte antigen (HLA)-matched bone marrow transplantation, transplanting male patients with grafts from female donors has been associated with a higher incidence of graft-versus-host disease (GVHD) and of nonrelapse mortality (NRM). The aim of the current analysis was to compare transplantation outcomes in male patients given female unrelated cord blood (UCB) versus other gender combinations. Patients and methods Data from 552 consecutive patients with acute myeloid leukemia (AML) given a single UCB transplantation between 2000 and 2014 were included. Results In comparison with other gender combination, male patients given female UCB (n = 131) had a trend for a higher incidence of grades II–IV acute GVHD (33 versus 25 %, P = 0.08), a trend for a higher incidence of NRM (41 versus 33 %, P = 0.06), and a lower leukemia-free (LFS, 30 versus 41 %, P = 0.01) and overall survival (OS, 33 versus 45 %, P = 0.008). In multivariate analyses, taking into consideration all patients for which data on HLA-matching and cell dose transplanted were fully available (n = 363), male patients transplanted with a female UCB had a trend for a higher incidence of grade III–IV acute GVHD (hazard ratio (HR) = 2.0, P = 0.06), a trend for a higher NRM (HR = 1.5, P = 0.06), and a worse LFS (HR = 1.4, P = 0.04) and OS (HR = 1.3, P = 0.06). Conclusions Our data suggest that male patients transplanted with female UCB might have higher risk of acute GVHD and of NRM leading to worse LFS and OS. These results should be confirmed in other large cohorts of patients before used for determining the choice of an UCB unit. Electronic supplementary material The online version of this article (doi:10.1186/s13045-015-0207-4) contains supplementary material, which is available to authorized users.

Published
2015

7. PECATI: A Multicentric, Open-Label, Single-Arm Phase II Study to Evaluate the Efficacy and Safety of Pembrolizumab and Lenvatinib in Pretreated B3-Thymoma and Thymic Carcinoma Patients

Author

Laurence Bigay-Game, Miguel Sampayo, Nicolas Girard, Laurent Greillier, Benjamin Besse, Javier de Castro, Jordi Remon, Sophie Cousin, R. Bernabé, Oscar Juan, Joaquin Mosquera, Silvia Novello, Centro Integral Oncologico Clara Campal, Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut Curie [Paris], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Università degli studi di Torino = University of Turin (UNITO), Hospital Universitario La Paz, Service de pneumologie [Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hospital Universitario Virgen del Rocío [Sevilla], Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Nord [CHU - APHM], Institut Bergonié [Bordeaux], UNICANCER, Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, Institut Gustave Roussy (IGR), and Université Paris-Saclay

Subjects
Pulmonary and Respiratory Medicine, Oncology, Cancer Research, medicine.medical_specialty, Lung Neoplasms, Thymoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, Second-line, Pembrolizumab, Antibodies, Monoclonal, Humanized, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Immunotherapy, Lenvatinib, Pembrolizumab, Second-line, Thymic epithelial tumors, chemistry.chemical_compound, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Lenvatinib, Humans, Medicine, Thymic epithelial tumors, Lung cancer, Survival rate, Thymic carcinoma, business.industry, Phenylurea Compounds, Standard treatment, Cancer, Thymus Neoplasms, medicine.disease, chemistry, Quinolines, [SDV.IMM]Life Sciences [q-bio]/Immunology, Immunotherapy, business
Abstract

International audience; Thymic epithelial tumors are rare neoplastic proliferations of thymic epithelial cells. The aggressiveness of these malignancies increases as higher is the histologic subtype, being thymic carcinoma the most aggressive subtype, with a greater tendency to metastatic spread. In metastatic setting, there is no standard treatment after progression on platinum-based chemotherapy. In this scenario, monotherapy treatment either with lenvatinib, a multi-tyrosine kinase inhibitor with antiangiogenic properties, or pembrolizumab, an immune-checkpoint inhibitor, has reported clinical activity. Potential combination of both agents may have synergistic activity as reported in other cancer types. PECATI trial is a single-arm, investigator-initiated phase II study aiming to assess the activity and safety of the combination of lenvatinib and pembrolizumab in 43 patients with advanced B3-thymoma or thymic carcinoma who progressed on or after at least one previous line of platinum-based chemotherapy. The primary endpoint of the trial is 5-month progression-free survival rate and the secondary endpoints include overall response rate, duration of response, and overall survival.

Published
2022

8. Systematic review and meta‐analysis: the incidence and prevalence of paediatric coeliac disease across Europe

Author

Osvaldo Borrelli, Christos Tzivinikos, Corina Pienar, Carmen Ribes-Koninckx, John Williams, Kym Thorne, Ilse Broekaert, Stephen E. Roberts, Javier Martín-de-Carpi, Ann John, Emmanuel Mas, Nikhil Thapar, Marc A. Benninga, Rut Anne Thomassen, Mike Thomson, Jernej Dolinsek, Sian Morrison-Rees, Erasmo Miele, Roberts, Stephen E, Morrison-Rees, Sian, Thapar, Nikhil, Benninga, Marc A, Borrelli, Osvaldo, Broekaert, Ilse, Dolinsek, Jernej, Martin-de-Carpi, Javier, Mas, Emmanuel, Miele, Erasmo, Pienar, Corina, Ribes-Koninckx, Carmen, Thomassen, Rut A, Thomson, Mike, Tzivinikos, Christo, Thorne, Kymberley, John, Ann, Williams, John G, Swansea University, Great Ormond Street Hospital for Children [London] (GOSH), University College of London [London] (UCL), Children’s Health Queensland [Brisbane] (CHQ), University of Amsterdam [Amsterdam] (UvA), University Hospital of Cologne [Cologne], University medical centre Maribor (UKC Maribor), Institut de Recerca Pediàtrica Hospital Sant Joan de Déu [Barcelona, Spain], Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 'Federico II' University of Naples Medical School, Victor Babeş University of Medicine and Pharmacy (UMFT), Hospital Universitari i Politècnic La Fe, Oslo University Hospital [Oslo], University of Sheffield [Sheffield], Al Jalila Children's Specialty Hospital, and European Society for Paediatric Gastroenterology Hepatology and Nutrition

Subjects
Pediatrics, medicine.medical_specialty, MEDLINE, Age at diagnosis, Cochrane Library, Asymptomatic, Coeliac disease, Serology, 03 medical and health sciences, 0302 clinical medicine, 030225 pediatrics, Prevalence, medicine, Humans, Pharmacology (medical), Child, Aged, Autoantibodies, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Hepatology, business.industry, Incidence, Incidence (epidemiology), Gastroenterology, Infant, medicine.disease, 3. Good health, Europe, Celiac Disease, Child, Preschool, Meta-analysis, 030211 gastroenterology & hepatology, medicine.symptom, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Background: Coeliac disease is one of the most prevalent immune-mediated gastrointestinal disorders in children. Aim: To review the incidence and prevalence of paediatric coeliac disease, and their trends, regionally across Europe, overall and according to age at diagnosis. Methods: Systematic review and meta-analysis from January 1, 1950 to December 31, 2019, based on PubMed, CINAHL and the Cochrane Library, searches of grey literature and websites and hand searching of reference lists. A total of 127 eligible studies were included. Results: The prevalence of previously undiagnosed coeliac disease from screening surveys (histology based) ranged from 0.10% to 3.03% (median = 0.70%), with a significantly increasing annual trend (P = 0.029). Prevalence since 2000 was significantly higher in northern Europe (1.60%) than in eastern (0.98%), southern (0.69%) and western (0.60%) Europe. Large increases in the incidence of diagnosed coeliac disease across Europe have reached 50 per 100 000 person-years in Scandinavia, Finland and Spain. The median age at diagnosis increased from 1.9 years before 1990 to 7.6 since 2000. Larger increases in incidence were found in older age groups than in infants and ages

Published
2021

9. Safety of Thiopurine Use in Paediatric Gastrointestinal Disease

Author

Jernej Dolinsek, Christos Tzivinikos, Rut Ann Thomassen, Erasmo Miele, Carmen Ribes-Koninckx, Nikhil Thapar, Rok Orel, Corina Pienar, Ilse Broekaert, Mike Thomson, Emmanuel Mas, Marc A. Benninga, 'Federico II' University of Naples Medical School, University of Amsterdam [Amsterdam] (UvA), University Hospital of Cologne [Cologne], University medical centre Maribor (UKC Maribor), Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University Medical Centre Ljubljana [Ljubljana, Slovenia] (UMCL), Victor Babeş University of Medicine and Pharmacy (UMFT), Hospital Universitari i Politècnic La Fe, Oslo University Hospital [Oslo], NHS Foundation Trust [London], The Royal Marsden, Al Jalila Children's Specialty Hospital, University College of London [London] (UCL), Queensland Paediatric Infectious Diseases Laboratory [Australia], University of Queensland [Brisbane]-Children's Health Research Centre, Paediatric Gastroenterology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ARD - Amsterdam Reproduction and Development, Miele, E., Benninga, M. A., Broekaert, I., Dolinsek, J., Mas, E., Orel, R., Pienar, C., Ribes-Koninckx, C., Thomassen, R. A., Thomson, M., Tzivinikos, C., and Thapar, N.

Subjects
Infliximab therapy, medicine.medical_specialty, Autoimmune hepatitis, Inflammatory bowel disease, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Gastrointestinal Agents, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Recurrence, inflammatory bowel disease, 030225 pediatrics, Steroid sparing, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Immunologic Factors, 6-mercaptopurine, Adverse effect, Intensive care medicine, Child, azathioprine, Thiopurine methyltransferase, biology, autoimmune hepatitis, Crohn disease, business.industry, Mercaptopurine, thiopurines, Gastroenterology, medicine.disease, Inflammatory Bowel Diseases, 3. Good health, Gastrointestinal disease, Pediatrics, Perinatology and Child Health, biology.protein, adverse effects, 030211 gastroenterology & hepatology, business, Immunosuppressive Agents, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Thiopurines, alone or in combination with other agents, have a pivotal role in the treatment of specific gastrointestinal and hepatological disorders. In inflammatory bowel disease and autoimmune hepatitis thiopurines have proven their value as steroid sparing agents for the maintenance of remission and may be considered for preventing postoperative Crohn disease recurrence where there is moderate risk of this occurring. Their use with infliximab therapy reduces antibody formation and increases biologic drug levels. The routine clinical use of thiopurines has, however, been questioned due to a number of potential adverse effects. The aim of this article is to provide information regarding the use, and in particular, safety of these agents in clinical practice in the light of such potentially severe, albeit rare, effects.

Published
2020

10. Cognitive impairment in multiple sclerosis: diagnosis and monitoring

Author

Angela Vidal-Jordana, Ricardo C Ginestal-López, Virginia Meca-Lallana, Francisco Pérez-Miralles, Joan Carreres-Polo, Francisco Gascón-Giménez, Nieves Téllez-Lara, Yolanda Higueras, Jesús Romero-Imbroda, Sara Eichau-Madueño, Institut Català de la Salut, [Meca-Lallana V] Unidad de Enfermedades Desmielinizantes, Servicio de Neurología, Hospital Universitario de La Princesa, Madrid, Spain. [Gascón-Giménez F] Unidad de Esclerosis Múltiple, Servicio de Neurología, Hospital Clínico Universitario, Valencia, Spain. [Ginestal-López RC] Servicio de Neurología, Hospital Clínico San Carlos, Madrid, Spain. [Higueras Y] Instituto de Investigación Sanitaria del Gregorio Marañón, Hospital Gregorio Marañón, Madrid, Spain. [Téllez-Lara N] Servicio de Neurología, Hospital Clínico Universitario, Valladolid, Spain. [Carreres-Polo J] Servicio de Radiología, Hospital Universitari i Politècnic La Fe de Valencia, Valencia, Spain. [Vidal-Jordana Á] Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (CEMCAT), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Esclerosi múltiple - Complicacions, medicine.medical_specialty, Neurology, Otros calificadores::/diagnóstico [Otros calificadores], Dermatology, Cognitive dysfunction, Multiple sclerosis, Neurophysiological monitoring, Neuropsychological tests, Multiple sclerosis, Otros calificadores::Otros calificadores::/complicaciones [Otros calificadores], Physical medicine and rehabilitation, Quality of life (healthcare), Cognitive dysfunction, Multidisciplinary approach, Neuropsychology, Other subheadings::/diagnosis [Other subheadings], Medicine, Humans, Neuropsychological assessment, Cognitive rehabilitation therapy, Tests neuropsicològics, Cognitive evaluation theory, medicine.diagnostic_test, business.industry, Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis [DISEASES], Cognition, General Medicine, Psychiatry and Mental health, Neuropsychological tests, Mental Disorders::Neurocognitive Disorders::Cognition Disorders::Cognitive Dysfunction [PSYCHIATRY AND PSYCHOLOGY], enfermedades del sistema nervioso::enfermedades autoinmunitarias del sistema nervioso::enfermedades autoinmunes desmielinizantes del SNC::esclerosis múltiple [ENFERMEDADES], Quality of Life, Original Article, Neurology (clinical), Neurophysiological monitoring, business, Trastorns de la cognició - Diagnòstic, trastornos mentales::trastornos neurocognitivos::trastornos cognitivos::disfunción cognitiva [PSIQUIATRÍA Y PSICOLOGÍA], Other subheadings::Other subheadings::/complications [Other subheadings]
Abstract

Introduction Cognitive impairment (CI) has a prevalence of 45–70% in people with multiple sclerosis (MS), producing a negative impact on their quality of life, personal life, and work. Early detection of CI has become an important aspect to be considered for an adequate follow-up, to optimize social adaptation and to implement specific cognitive rehabilitation strategies. The aim of this work is to propose a suitable cognitive evaluation of patients with MS based on available and efficient tools for diagnosis and monitoring purposes well supported by literature review and clinical experience. Methods A multidisciplinary panel of professionals from the field of neurology, neuropsychology, and neuroimaging performed a literature review of the topic of cognitive impairment assessment. This was combined and completed with their clinical experience to produce a set of recommendations. Results Some limitations to cognitive evaluation are described: shortage of time and resources during the neurology consultation, scarceness or absence of specialized professionals’ availability, importance of tests adaptation, and doubts about its use to define therapeutic efficiency. We recommend a baseline and annual screening evaluation, and we suggest a baseline and periodic neuropsychological assessment. The latter ought to change to a recommendation with the presence of either positive screening test, or subjective to cognitive complaints, screening-test results and patient or family report mismatch, or in specific social/work situations. Conclusions Cognitive evaluation should be performed on all patients diagnosed with MS and throughout follow-up. It is necessary to support the creation of multidisciplinary MS teams to optimize the evaluation and follow-up of MS patients.

Published
2021

11. First-line nivolumab plus ipilimumab with two cycles of chemotherapy versus chemotherapy alone (four cycles) in advanced non-small-cell lung cancer: CheckMate 9LA 2-year update

Author

X. Zhang, Michael Schenker, Shunyuan Lu, Arnaud Scherpereel, Maurice Pérol, A. Lingua, Manuel Cobo, S. Marimuthu, Tudor-Eliade Ciuleanu, Arteid Memaj, Eduardo Richardet, O. Juan-Vidal, F. Reyes, David P. Carbone, B. Zurawski, A. Alexandru, Phuong Tran, Hiroshi Sakai, Jaafar Bennouna, Martin Reck, Enriqueta Felip, Thomas John, Juliana Janoski de Menezes, Pierre-Jean Souquet, C. Martin, Luis Paz-Ares, P. De Marchi, German Center for Lung Research, Institutul oncologic Prof Dr Ion Chiricuta [Cluj-Napoca, Romania], Instituto de Investigación Biomédica [Malaga, Spain] (IBIMA), SF Nectarie Oncology Center [Craiova, Romania], Ambulatorium Chemioterapii [Bydgoszcz, Poland] (AC), Hospital Nossa Senhora Da Conceição [Porto Alegre, Brazil] (HNSDC), Instituto Oncológico De Córdoba [Córdoba, Argentina] (IODC), Immunogenic Cell Death and Mesothelioma Therapy (CRCINA-ÉQUIPE 4), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Vall d'Hebron University Hospital [Barcelona], Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, Oncology Institute of Bucharest Professor Doctor Alexandru Trestioreanu [Bucharest, Romania] (OIB), Saitama Cancer Center [Saitama, Japan] (S2C), Instituto Medico Rio Cuarto SA [Córdoba, Argentina] (IMRC), Fundacion Arturo Lopez Perez [Santiago, Metropolitana, Chile] (FALP), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Barretos Cancer Hospital [São Paulo, Brazil] (BCH), Instituto Alexander Fleming [Buenos Aires, Argentina] (IAF), Centre Léon Bérard [Lyon], 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), Shanghai Jiaotong University, Hospital Universitario 12 de Octubre [Madrid], Ohio State University [Columbus] (OSU), Bristol-Myers Squibb [Princeton], Austin Hospital [Melbourne], Austin Health, Bernardo, Elizabeth, Institut Català de la Salut, [Reck M] Department of Thoracic Oncology, Airway Research Center North, German Center for Lung Research, LungClinic, Grosshansdorf, Germany. [Ciuleanu TE] Department of Oncology, Institutul Oncologic Prof Dr Ion Chiricuta and UMF Iuliu Hatieganu, Cluj-Napoca, Romania. [Cobo M] Department of Medical Oncology, Unidad de Gestión Clínica Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria, IBIMA, Málaga, Spain. [Schenker M] Department of Oncology, SF Nectarie Oncology Center, Craiova, Romania. [Zurawski B] Department of Clinical Oncology, Ambulatorium Chemioterapii, Bydgoszcz, Poland. [Menezes J] Department of Oncology, Hospital Nossa Senhora da Conceição, Porto Alegre, Brazil. [Felip E] 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
Oncology, Cancer Research, medicine.medical_specialty, Lung Neoplasms, medicine.medical_treatment, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Ipilimumab, [SDV.CAN]Life Sciences [q-bio]/Cancer, Other subheadings::Other subheadings::/drug therapy [Other subheadings], NSCLC, Quimioteràpia combinada, nivolumab, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Carcinoma, Non-Small-Cell Lung, Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, first-line, ipilimumab, Lung cancer, Adverse effect, NSCLC, dual immunotherapy, first-line, ipilimumab, nivolumab, Original Research, Chemotherapy, business.industry, Hazard ratio, terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms::Bronchial Neoplasms::Carcinoma, Bronchogenic::Carcinoma, Non-Small-Cell Lung [DISEASES], neoplasias::neoplasias por localización::neoplasias torácicas::neoplasias del tracto respiratorio::neoplasias pulmonares::neoplasias de los bronquios::carcinoma broncogénico::carcinoma de pulmón de células no pequeñas [ENFERMEDADES], medicine.disease, Confidence interval, Discontinuation, Nivolumab, dual immunotherapy, Neoplasm Recurrence, Local, business, Corrigendum, Pulmons - Càncer - Tractament, medicine.drug
Abstract

Background To further characterize survival benefit with first-line nivolumab plus ipilimumab with two cycles of chemotherapy versus chemotherapy alone, we report updated data from the phase III CheckMate 9LA trial with a 2-year minimum follow-up. Patients and methods Adult patients were treatment naïve, with stage IV/recurrent non-small-cell lung cancer, no known sensitizing EGFR/ALK alterations, and an Eastern Cooperative Oncology Group performance status ≤1. Patients were randomized 1 : 1 to nivolumab 360 mg every 3 weeks plus ipilimumab 1 mg/kg every 6 weeks with two cycles of chemotherapy, or four cycles of chemotherapy. Updated efficacy and safety outcomes are reported, along with progression-free survival (PFS) after next line of treatment (PFS2), treatment-related adverse events (TRAEs) by treatment cycle, and efficacy outcomes in patients who discontinued all treatment components in the experimental arm due to TRAEs. Results With a median follow-up of 30.7 months, nivolumab plus ipilimumab with chemotherapy continued to prolong overall survival (OS) versus chemotherapy. Median OS was 15.8 versus 11.0 months [hazard ratio 0.72 (95% confidence interval 0.61-0.86)]; 2-year OS rate was 38% versus 26%. Two-year PFS rate was 20% versus 8%. ORR was 38% versus 25%, respectively; 34% versus 12% of all responses were ongoing at 2 years. Median PFS2 was 13.9 versus 8.7 months. Improved efficacy outcomes in the experimental versus control arm were observed across most subgroups, including by programmed death-ligand 1 and histology. No new safety signals were observed; onset of grade 3/4 TRAEs was mostly observed during the first two treatment cycles in the experimental arm. In patients who discontinued all components of nivolumab plus ipilimumab with chemotherapy treatment due to TRAEs (n = 61) median OS was 27.5 months; 56% of responders had an ongoing response ≥1 year after discontinuation. Conclusions With a 2-year minimum follow-up, nivolumab plus ipilimumab with two cycles of chemotherapy provided durable efficacy benefits over chemotherapy with a manageable safety profile and remains an efficacious first-line treatment of advanced non-small-cell lung cancer., Highlights • Nivolumab + ipilimumab + two cycles of chemotherapy (chemo) significantly prolonged survival versus chemo in first-line advanced NSCLC. • At 2 years, overall survival benefits were durable with nivolumab + ipilimumab + chemo versus chemo. • Benefits of nivolumab + ipilimumab + chemo were seen across most patient subgroups, including by PD-L1 and histology. • Discontinuing nivolumab + ipilimumab + chemo due to treatment-related AEs did not negatively impact long-term benefits. • Nivolumab + ipilimumab + two cycles of chemo is an efficacious first-line treatment option for advanced non-oncogene-driven NSCLC.

Published
2021

12. Drugs in Focus: Octreotide Use in Children With Gastrointestinal Disorders

Author

Osvaldo Borrelli, Erasmo Miele, C Ribes Koninckx, Rut Ann Thomassen, J Martin de-Carpi, Marc A. Benninga, Ilse Broekaert, Jernej Dolinsek, Christo Tzivinikos, Corina Pienar, Emmanuel Mas, Mike Thomson, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Great Ormond Street Hospital for Children [London] (GOSH), University Hospital of Cologne [Cologne], University medical centre Maribor (UKC Maribor), 'Federico II' University of Naples Medical School, Victor Babeş University of Medicine and Pharmacy (UMFT), University of Amsterdam [Amsterdam] (UvA), Vall d'Hebron University Hospital [Barcelona], Hospital Universitari i Politècnic La Fe, Oslo University Hospital [Oslo], Sheffield Children's NHS Foundation Trust, Al Jalila Children's Specialty Hospital, and VU University Medical Center [Amsterdam]

Subjects
medicine.medical_specialty, Gastrointestinal bleeding, Gastrointestinal Diseases, Octreotide, Lymphangiectasia, somatostatin, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Gastrointestinal Agents, children, Chylous ascites, Internal medicine, chylous ascites, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Child, business.industry, Chylothorax, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, bleeding, 3. Good health, Clinical trial, diarrhoea, Pancreatitis, Pharmaceutical Preparations, ocreotide, 030220 oncology & carcinogenesis, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Acute Disease, Pediatrics, Perinatology and Child Health, Acute pancreatitis, 030211 gastroenterology & hepatology, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract

International audience; Octreotide, a somatostatin analogue, has been used for more than 20 years in children with gastrointestinal bleeding, chylothorax or chylous ascites, intestinal lymphangiectasia, pancreatitis, intestinal dysmotility, and severe diarrhoea; however, until now, there is a lack of randomised clinical trials evaluating the efficacy of this compound in childhood. Hence, we aimed to review the literature in order to determine the evidence of its use and safety in children, using PubMed from 2000 to 2021 with the search terms "octreotide" and "children" and "bleeding or chylous ascites or chylothorax or acute pancreatitis or lymphangiectasia or diarrhoea or intestinal dysmotility".

Published
2021

13. Liver transplantation for patients with acute-on-chronic liver failure (ACLF) in Europe: Results of the ELITA/EF-CLIF collaborative study (ECLIS)

Author

Luca S. Belli, Christophe Duvoux, Thierry Artzner, William Bernal, Sara Conti, Paolo A. Cortesi, Sophie-Caroline Sacleux, George-Philippe Pageaux, Sylvie Radenne, Jonel Trebicka, Javier Fernandez, Giovanni Perricone, Salvatore Piano, Silvio Nadalin, Maria C. Morelli, Silvia Martini, Wojciech G. Polak, Krzysztof Zieniewicz, Christian Toso, Marina Berenguer, Claudia Iegri, Federica Invernizzi, Riccardo Volpes, Vincent Karam, René Adam, François Faitot, Liane Rabinovich, Faouzi Saliba, Lucy Meunier, Mickael Lesurtel, Frank E. Uschner, Costantino Fondevila, Baptiste Michard, Audrey Coilly, Magdalena Meszaros, Domitille Poinsot, Andreas Schnitzbauer, Luciano G. De Carlis, Roberto Fumagalli, Paolo Angeli, Vincente Arroyo, Rajiv Jalan, Raffaella Viganò, Chiara Mazzarelli, Andrea Lauterio, Alessandro Giacomoni, Francesca Donato, Pietro Lampertico, Luisa Pasulo, Stefano Fagiuoli, Michele Colledan, Maria Cristina Morelli, Giovanni Vitale, Damiano Patrono, Renato Romagnoli, Antonio Ottobrelli, Ioannis Petridis, Umberto Cillo, Giacomo Germani, Patrizia Burra, Philippe Bachellier, Pietro Addeo, Camille Besch, Francoise Faitot, Sophie Caroline Sacleux, Saliba Faouzi, Rene Adam, Didier Samuel, Celine Guichon, Stéfanie Faure, Josè Ursic-Bedoya, Jorde Colmenero, David Toapanta, María Hernández-Tejero, Carmen Vinaixa, Caroline den Hoed, Jubi E. de Haan, Andrea Della Penna, Frank Erhard Uschner, Martin Welker, Stefan Zeuzem, Wolf Bechstein, Nicolas Goossens, Joanna Raszeja-Wyszomirska, Dev Katarey, Banwari Agarwal, Surgery, Internal Medicine, Gastroenterology & Hepatology, Intensive Care, ASST Great Metropolitan Niguarda / ASST Grande Ospedale Metropolitano Niguarda [Milan, Italia], Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital de Hautepierre [Strasbourg], King‘s College London, Ospedale Multimedica Sesto San Giovanni, Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Centre Hépato-Biliaire [Hôpital Paul Brousse] (CHB), Hôpital Paul Brousse-Assistance Publique - Hôpitaux de Paris, Physiopathologie et traitement des maladies du foie, Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Département d'Hépato-Gastroentérologie et de Transplantation Hépatique [CHU Saint-Eloi], Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Service d'Hépatologie [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Goethe-University Frankfurt am Main, European Foundation for Study of Chronic Liver Failure [Barcelona] (EF CLIF), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Liver Unit, Clínica Universitaria, CIBER-EHD, Azienda Ospedale Università di Padova = Hospital-University of Padua (AOUP), Universitätsklinikum Tübingen - University Hospital of Tübingen, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Azienda Ospedaliero-Universitaria di Bologna, Azienda Ospedalerio - Universitaria Città della Salute e della Scienza di Torino = University Hospital Città della Salute e della Scienza di Torino, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Medical University of Warsaw - Poland, Geneva University Hospitals and Geneva University, Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, Hospital Papa Giovanni XXIII (Hosp P Giovanni XXIII), Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (ISMETT), Pôle des Pathologies Digestives Hépatiques et Transplantation [Hôpital Hautepierre-Strasbourg], Department of Physiopatology and Transplantation, University of Milan (DEPT), Università degli Studi di Milano = University of Milan (UNIMI), Ospedale S. Giovanni Battista-Molinette, Azienda Ospedaliera di Padova, Università degli Studi di Padova = University of Padua (Unipd), Hospital Clinic i Provincial de Barcelona (SCReN), University College London Hospitals (UCLH), Belli, L, Duvoux, C, Artzner, T, Bernal, W, Conti, S, Cortesi, P, Sacleux, S, Pageaux, G, Radenne, S, Trebicka, J, Fernandez, J, Perricone, G, Piano, S, Nadalin, S, Morelli, M, Martini, S, Polak, W, Zieniewicz, K, Toso, C, Berenguer, M, Iegri, C, Invernizzi, F, Volpes, R, Karam, V, Adam, R, Faitot, F, Rabinovich, L, Saliba, F, Meunier, L, Lesurtel, M, Uschner, F, Fondevila, C, Michard, B, Coilly, A, Meszaros, M, Poinsot, D, Schnitzbauer, A, De Carlis, L, Fumagalli, R, Angeli, P, Arroyo, V, Jalan, R, Fagiuoli, S, Goossens, Nicolas, and Salvy-Córdoba, Nathalie

Subjects
Male, 0301 basic medicine, Multi-drug resistant organisms, medicine.medical_treatment, Waiting list, Salvage therapy, Liver transplantation, Severity of Illness Index, MESH: Proportional Hazards Models, Cohort Studies, 0302 clinical medicine, MESH: Risk Factors, Risk Factors, Medicine, MESH: Cohort Studies, Acute-on-Chronic Liver Failure, MESH: Aged, High rate, MESH: Middle Aged, ddc:617, Hazard ratio, MESH: Acute-On-Chronic Liver Failure, Middle Aged, Prognosis, Predictive factors, Italy, Female, 030211 gastroenterology & hepatology, Adult, MESH: Liver Transplantation, medicine.medical_specialty, MESH: Prognosis, 03 medical and health sciences, MESH: Severity of Illness Index, Internal medicine, Humans, Acute on chronic liver failure, Renal replacement therapy, Aged, Proportional Hazards Models, Retrospective Studies, MESH: Humans, Hepatology, business.industry, MESH: Italy, MESH: Adult, MESH: Retrospective Studies, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Retrospective cohort study, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Multi-drug resistant organism, MESH: Male, 030104 developmental biology, Predictive factor, business, MESH: Female
Abstract

Background & Aims: Liver transplantation (LT) has been proposed as an effective salvage therapy even for the sickest patients with acute-on-chronic liver failure (ACLF). This large collaborative study was designed to assess the current clinical practice and outcomes of patients with ACLF who are wait-listed for LT in Europe. Methods: This was a retrospective study including 308 consecutive patients with ACLF, listed in 20 centres across 8 European countries, from January 2018 to June 2019. Results: A total of 2,677 patients received a LT: 1,216 (45.4%) for decompensated cirrhosis. Of these, 234 (19.2%) had ACLF at LT: 58 (4.8%) had ACLF-1, 78 (6.4%) had ACLF-2, and 98 (8.1%) had ACLF-3. Wide variations were observed amongst countries: France and Germany had high rates of ACLF-2/3 (27-41%); Italy, Switzerland, Poland and the Netherlands had medium rates (9-15%); and the United Kingdom and Spain had low rates (3-5%) (p 4 mmol/L (hazard ratio [HR] 3.14; 95% CI 1.37-7.19), recent infection from multidrug resistant organisms (HR 3.67; 95% CI 1.63-8.28), and renal replacement therapy (HR 2.74; 95% CI 1.37-5.51) were independent predictors of post-LT mortality. During the same period, 74 patients with ACLF died on the waiting list. In an intention-to-treat analysis, 1-year survival of patients with ACLF on the LT waiting list was 73% for ACLF-1 or-2 and 50% for ACLF-3. Conclusion: The results reveal wide variations in the listing of patients with ACLF in Europe despite favourable post-LT survival. Risk factors for mortality were identified, enabling a more pre-cise prognostic assessment of patients with ACLF. Lay summary: Acute-on-chronic liver failure (ACLF) is a severe clinical condition for which liver transplantation is an effective therapeutic option. This study has demonstrated that in Europe, referral and access to liver transplantation (LT) for patients with ACLF needs to be harmonised to avoid inequities. Post-LT survival for patients with ACLF was >80% after 1 year and some factors have been identified to help select patients with favourable outcomes. (C) 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All reserved.

Published
2021

14. Drugs in Focus: The Use of Racecadotril in Paediatric Gastrointestinal Disease

Author

Emmanuel Mas, Ilse Broekaert, Erasmo Miele, Christos Tzivinikos, Jernej Dolinsek, Carmen Ribes-Koninckx, Marc A. Benninga, Corina Pienar, Rut Anne Thomassen, Nikhil Thapar, Rok Orel, Mike Thomson, Victor Babeş University of Medicine and Pharmacy (UMFT), Emma Children’s Hospital Academic Medical Centre, University Hospital of Cologne, University medical centre Maribor (UKC Maribor), Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Università degli studi di Napoli Federico II, University Medical Centre Ljubljana [Ljubljana, Slovenia] (UMCL), Hospital Universitario y Politécnico La Fe, Oslo University Hospital [Oslo], NHS Foundation Trust, Al Jalila Children's Specialty Hospital, UCL Great Ormond Street Institute of Child Health [London, UK], Great Ormond Street Hospital, Partenaires INRAE, Queensland Children's Hospital, Pienar, Corina, Benninga, Marc A, Broekaert, Ilse J, Dolinsek, Jernej, Mas, Emmanuel, Miele, Erasmo, Orel, Rok, Ribes-Koninckx, Carmen, Thomassen, Rut-Anne, Thomson, Mike, Tzivinikos, Christo, Thapar, Nikhil, Paediatric Gastroenterology, AGEM - Digestive immunity, AGEM - Re-generation and cancer of the digestive system, Amsterdam Reproduction & Development (AR&D), ProdInra, Migration, University of Naples Federico II = Università degli studi di Napoli Federico II, and Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe

Subjects
Diarrhea, Drug, Thiorphan, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Gastrointestinal Diseases, medicine.drug_class, media_common.quotation_subject, medicine.medical_treatment, Pharmacology, Racecadotril, 03 medical and health sciences, 0302 clinical medicine, adjuvant, 030225 pediatrics, Antidiarrhoeal, medicine, Humans, Antidiarrheals, Child, Adverse effect, Neprilysin, media_common, racecadotril, business.industry, digestive, oral, and skin physiology, Gastroenterology, medicine.disease, Small intestine, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, 3. Good health, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, medicine.anatomical_structure, Pharmaceutical Preparations, Gastrointestinal disease, Pediatrics, Perinatology and Child Health, 030211 gastroenterology & hepatology, business, gastroenteritis, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Adjuvant, medicine.drug
Abstract

International audience; Acute diarrhoea is a leading cause of morbidity and mortality in the paediatric population. Racecadotril is an antisecretory drug recommended as an adjuvant anti-diarrhoeal treatment.In the small bowel, the enzyme neutral endopeptidase (NEP) inhibits the action of enkephalins, which prevent water and electrolyte hypersecretion. By inhibiting NEP, racecadotril allows enkephalins to exhibit their antisecretory effects. Consequently, racecadotril reduces the secretion of water and electrolytes in the small intestine, without having an effect on intestinal motility. No serious adverse events related to racecadotril have been reported.Racecadotril has proven its efficacy as an adjuvant anti-diarrhoeal drug with a good safety profile. Its addition to oral rehydration solution (ORS) appears clinically beneficial and potentially leads to health care savings.

Published
2020

15. Drug clearance in neonates : a combination of population pharmacokinetic modelling and machine learning approaches to improve individual prediction

Author

Yue-E Wu, Alison H. Thomson, Yi Zheng, José Esteban Peris, Lo Yl, Bernd Meibohm, Edmund V. Capparelli, Wei Zhao, John N. van den Anker, Irja Lutsar, Hai-Yan Shi, Hai-Yan Xu, Xiao Li, Stéphanie Leroux, Karel Allegaert, Evelyne Jacqz-Aigrain, Bo Hao Tang, Yue Zhou, Xin Huang, Xiaoling Wang, Bao-Ping Xu, Bu-Fan Yao, Jacobus Burggraaf, Nicolas Simon, A.-Dong Shen, Chen Kou, Guo-Xiang Hao, Efthymios Manolis, Tian-You Wang, Remedios Marques, Valérie Biran, Jumpei Saito, Zheng Guan, Wen-Qi Wang, Shandong University, Leiden University Medical Center (LUMC), Universiteit Leiden, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), European Medicines Agency [Amsterdam, Pays-Bas] (EMA), Hôpital Sud [CHU Rennes], CHU Pontchaillou [Rennes], Shandong Jiaotong University [Jinan], Capital University of Medical Sciences [Beijing] (CUMS), University of Strathclyde [Glasgow], University of California [San Diego] (UC San Diego), University of California (UC), Hôpital Robert Debré, 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), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), The University of Tennessee Health Science Center [Memphis] (UTHSC), University of Malaya = Universiti Malaya [Kuala Lumpur, Malaisie] (UM), Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, Universitat de València (UV), University of Tartu, National Center for Child Health and Development [Tokyo], Centre d'Investigation Clinique 1426 (CIC 1426), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Georgetown University [Washington] (GU), University Children's Hospital [Basel, Switzerland]], and Malbec, Odile

Subjects
SELECTION, 0301 basic medicine, RM, BIG DATA, AZLOCILLIN, Metabolic Clearance Rate, [SDV]Life Sciences [q-bio], education, 030106 microbiology, Population, Drug Elimination Routes, Body weight, Machine learning, computer.software_genre, Models, Biological, 030226 pharmacology & pharmacy, CLASSIFICATION, Machine Learning, 03 medical and health sciences, 0302 clinical medicine, Text mining, Pharmacokinetics, Vancomycin, REGRESSION, Covariate, Humans, Medicine, Pharmacology (medical), CROSS-VALIDATION, Combined method, Pharmacology, education.field_of_study, PRETERM, business.industry, Infant, Newborn, CEFEPIME, DOSING OPTIMIZATION, [SDV] Life Sciences [q-bio], YOUNG, Artificial intelligence, business, computer, Clearance, Predictive methods
Abstract

International audience; Background Population pharmacokinetic evaluations have been widely used in neonatal pharmacokinetic studies, while machine learning has become a popular approach to solving complex problems in the current era of big data. Objective The aim of this proof-of-concept study was to evaluate whether combining population pharmacokinetic and machine learning approaches could provide a more accurate prediction of the clearance of renally eliminated drugs in individual neonates. Methods Six drugs that are primarily eliminated by the kidneys were selected (vancomycin, latamoxef, cefepime, azlocillin, ceftazidime, and amoxicillin) as 'proof of concept' compounds. Individual estimates of clearance obtained from population pharmacokinetic models were used as reference clearances, and diverse machine learning methods and nested cross-validation were adopted and evaluated against these reference clearances. The predictive performance of these combined methods was compared with the performance of two other predictive methods: a covariate-based maturation model and a postmenstrual age and body weight scaling model. Relative error was used to evaluate the different methods. Results The extra tree regressor was selected as the best-fit machine learning method. Using the combined method, more than 95% of predictions for all six drugs had a relative error of < 50% and the mean relative error was reduced by an average of 44.3% and 71.3% compared with the other two predictive methods. Conclusion A combined population pharmacokinetic and machine learning approach provided improved predictions of individual clearances of renally cleared drugs in neonates. For a new patient treated in clinical practice, individual clearance can be predicted a priori using our model code combined with demographic data. Bo-Hao Tang and Zheng Guan contributed equally to this work.

Published
2021

16. Sucrosomial Iron Supplementation for the Treatment of Iron Deficiency Anemia in Inflammatory Bowel Disease Patients Refractory to Oral Iron Treatment

Author

V. Robles, Pilar Nos, Claudia Herrera-de Guise, Alicia Algaba, Yolanda Ber Nieto, Guillermo Bastida, Esteban Sáez-González, Fernando Gomollón, Jose Manuel Soares, Fernando Bermejo, Institut Català de la Salut, [Bastida G] Department of Gastroenterology, CIBEREHD, Hospital Universitari i Politècnic La Fe, 46026 Valencia, Spain. [Herrera-de Guise C, Robles V] Unitat d'Atenció a la Colitis de Crohn, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Algaba A] Department of Gastroenterology, Instituto de Investigación Sanitaria Hospital La Paz (IdiPaz), Hospital Universitario de Fuenlabrada, 28046 Madrid, Spain. [Ber Nieto Y] Department of Gastroenterology, Hospital Universitario San Jorge, 22004 Huesca, Spain. [Soares JM] Department of Gastroenterology, Hospital Pedro Hispano, 4454-509 Matosinhos, Portugal, Vall d'Hebron Barcelona Hospital Campus, and Servicio de Digestivo. Hospital Universitario de Fuenlabrada

Subjects
enfermedades nutricionales y metabólicas::enfermedades metabólicas::trastornos del metabolismo del hierro::anemia ferropénica [ENFERMEDADES], Male, Inorganic Chemicals::Elements::Metals, Heavy::Iron [CHEMICALS AND DRUGS], Administration, Oral, Gastroenterology, Inflammatory bowel disease, Ferric Compounds, Intestins - Inflamació - Tractament, enfermedades del sistema digestivo::enfermedades gastrointestinales::gastroenteritis::enfermedad inflamatoria intestinal [ENFERMEDADES], Hemoglobins, Enfermedades Inflamatorias del Intestino, 0302 clinical medicine, iron deficiency, Quality of life, Surveys and Questionnaires, Compuestos de Hierro, Anèmia ferropènica - Tractament, TX341-641, Prospective Studies, Prospective cohort study, Depression (differential diagnoses), Aged, 80 and over, Nutrition and Dietetics, Anemia, Iron-Deficiency, sucrosomial iron, Iron deficiency, Middle Aged, anemia, humanities, compuestos inorgánicos::elementos::metales pesados::hierro [COMPUESTOS QUÍMICOS Y DROGAS], Anemia Ferropénica, Treatment Outcome, Tolerability, 030220 oncology & carcinogenesis, Other subheadings::Other subheadings::/administration & dosage [Other subheadings], 030211 gastroenterology & hepatology, Female, Adult, medicine.medical_specialty, Anemia, Iron, Article, 03 medical and health sciences, Young Adult, inflammatory bowel disease, Internal medicine, medicine, Humans, Ferro - Metabolisme - Ús terapèutic, Digestive System Diseases::Gastrointestinal Diseases::Gastroenteritis::Inflammatory Bowel Diseases [DISEASES], Aged, Otros calificadores::Otros calificadores::/administración & dosificación [Otros calificadores], Nutrition. Foods and food supply, business.industry, iron supplementation, Nutritional and Metabolic Diseases::Metabolic Diseases::Iron Metabolism Disorders::Anemia, Iron-Deficiency [DISEASES], medicine.disease, Inflammatory Bowel Diseases, Trace Elements, Iron-deficiency anemia, Dietary Supplements, Quality of Life, business, Iron Compounds, Food Science
Abstract

Iron deficiency anemia (IDA) is a common manifestation of Inflammatory Bowel Disease (IBD). Oral iron supplements are the treatment of choice, but are not always well tolerated. Sucrosomial® iron (SI) may represent an alternative. This prospective study assessed the tolerability and effectiveness of SI, and quality of life (QoL) of IDA-IBD patients who were intolerant to oral iron salts. The study included 52 individuals treated with 1 capsule/day for 12 weeks. Tolerability was assessed through a gastrointestinal symptom severity questionnaire. Hemoglobin (Hb) levels and clinical symptoms of IDA were analyzed. QoL was assessed using IBDQ-9 and EuroQoL questionnaires. The percentage of patients with excellent/good health increased from 42.9% to 94.3%. Mean Hb concentration significantly increased at all follow-up visits (p &lt, 0.05). Almost all participants (96.9%) were adherent to the study medication. Patients’ QoL improved (IBDQ-9: from 60.9 to 65.5). Patients also improved in mobility (71.8% to 78.1%), usual activities (51.3% to 68.7%), pain/discomfort (41.0% to 53.1%), and extreme depression/anxiety problems (7.7% to 3.2%), they worsened in self-care (100% to 90.6%), but perceived an enhancement in their global health [EQ-VAS score: 61.9 (±26.1) to 66.9 (±20.3)]. SI was well tolerated and improved IDA symptoms, IBD activity, and patients’ QoL. In conclusion, SI should be considered in IDA–IBD patients.

Published
2021
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17. First-line nivolumab (NIVO) plus ipilimumab (IPI) plus two cycles of chemotherapy (chemo) versus chemo alone (4 cycles) in patients with advanced non-small cell lung cancer (NSCLC): Two-year update from CheckMate 9LA

Author

Phuong Tran, Aurella Alexandru, S. Marimuthu, Tudor-Eliade Ciuleanu, Hiroshi Sakai, Manuel Cobo, Luis Paz-Ares, Michael Schenker, Jaafar Bennouna, Arnaud Scherpereel, Arteid Memaj, Enriqueta Felip, O. Juan-Vidal, David P. Carbone, B. Zurawski, Thomas John, Eduardo Richardet, Juliana Janoski de Menezes, Shun Lu, Martin Reck, German Center for Lung Research, Institutul oncologic Prof Dr Ion Chiricuta [Cluj-Napoca, Romania], Instituto de Investigación Biomédica [Malaga, Spain] (IBIMA), SF Nectarie Oncology Center [Craiova, Romania], Ambulatorium Chemioterapii [Bydgoszcz, Poland] (AC), Hospital Nossa Senhora Da Conceição [Porto Alegre, Brazil] (HNSDC), Instituto Oncológico De Córdoba [Córdoba, Argentina] (IODC), Immunogenic Cell Death and Mesothelioma Therapy (CRCINA-ÉQUIPE 4), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Vall d'Hebron University Hospital [Barcelona], Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, Oncology Institute of Bucharest Professor Doctor Alexandru Trestioreanu [Bucharest, Romania] (OIB), Saitama Cancer Center [Saitama, Japan] (S2C), 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), Shanghai Jiaotong University, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Ohio State University [Columbus] (OSU), Bristol-Myers Squibb [Princeton], Bristol Myers Squibb [Springfield, PA, USA] (BMS), Austin Hospital [Melbourne], Austin Health, and Bernardo, Elizabeth

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Chemotherapy, business.industry, medicine.medical_treatment, First line, Checkmate, non-small cell lung cancer (NSCLC), Ipilimumab, [SDV.CAN]Life Sciences [q-bio]/Cancer, medicine.disease, stomatognathic diseases, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, hemic and lymphatic diseases, medicine, Overall survival, In patient, Nivolumab, business, neoplasms, medicine.drug
Abstract

9000 Background: In the randomized phase 3 CheckMate 9LA trial (NCT03215706), first-line NIVO + IPI combined with 2 cycles of chemo significantly improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) vs chemo alone (4 cycles). Clinical benefit was observed regardless of programmed death ligand 1 (PD-L1) expression level and histology. Here we report data with 2 years’ minimum follow-up from this study. Methods: Adult patients (pts) with stage IV / recurrent NSCLC, ECOG performance status ≤ 1, and no known sensitizing EGFR/ALK alterations were stratified by PD-L1 (< 1% vs ≥ 1%), sex, and histology (squamous vs non-squamous) and were randomized 1:1 to NIVO 360 mg Q3W + IPI 1 mg/kg Q6W + chemo (2 cycles; n = 361) or chemo alone (4 cycles; n = 358). Pts with non-squamous NSCLC in the chemo-alone arm could receive pemetrexed maintenance. The primary endpoint was OS. Secondary endpoints included PFS and ORR by blinded independent central review, and efficacy by different PD-L1 levels. Safety was exploratory. Results: At a minimum follow-up of 24.4 months for OS (database lock: Feb 18, 2021), pts treated with NIVO + IPI + chemo continued to derive OS benefit vs chemo, with a median OS of 15.8 months vs 11.0 months, respectively (HR, 0.72 [95% CI, 0.61–0.86]); 2-year OS rates were 38% vs 26%. Median PFS with NIVO + IPI + chemo vs chemo was 6.7 months vs 5.3 months (HR, 0.67 [95% CI, 0.56–0.79]); 8% and 37% of pts who had disease progression received subsequent immunotherapy, respectively. ORR was 38% with NIVO + IPI + chemo vs 25% with chemo. Similar clinical benefit with NIVO + IPI + chemo vs chemo was observed in all randomized pts and across the majority of subgroups, including by PD-L1 expression level (Table) or histology. Any grade and grade 3–4 treatment-related adverse events were reported in 92% and 48% of pts in the NIVO + IPI + chemo arm vs 88% and 38% in the chemo arm, respectively. Conclusion: With 2 years’ minimum follow-up, first-line NIVO + IPI + chemo demonstrated durable survival and benefit versus chemo in pts with advanced NSCLC; no new safety signals were identified. Clinical trial information: NCT03215706. [Table: see text]

Published
2021

18. Brain region volumes and their relationship with disability progression and cognitive function in primary progressive multiple sclerosis

Author

Guillermo Izquierdo, Jorge Maurino, Lluís Ramió-Torrentà, Bonaventura Casanova, Daniel Prefasi, Jose R. Ara, Francisco Pérez-Miralles, Lucienne Costa-Frossard, Oscar Fernandez, Virginia Meca-Lallana, Antonio García-Merino, María L Martínez-Ginés, Sara Moreno-García, Francisco Gascón-Giménez, Joan Carreres-Polo, Institut Català de la Salut, [Pérez-Miralles FC] Neuroimmunology Unit, Department of Neurology, Hospital Universitari i Politècnic La Fe, Valencia, Spain. [Prefasi D] Department of Medical, Roche Farma S.A, Madrid, Spain. [García-Merino A] Department of Neurology, Hospital Universitario Puerta de Hierro, Majadahonda, Spain. [Ara JR] Department of Neurology, Hospital Universitario Miguel Servet, Zaragoza, Spain.[Izquierdo G] Department of Neurology, Hospital Universitario Virgen Macarena, Seville, Spain. [Meca-Lallana V] Department of Neurology, Hospital Universitario La Princesa, Madrid, Spain. [Ramió-Torrentà L] Unitat de Neuroimmunologia i Esclerosi Múltiple, Departament de Neurologia, Hospital Universitari de Girona Dr. Josep Trueta, Institut Català de la Salut (ICS), Girona, Spain. Institut d’Assistència Sanitària, Salt, Spain. Institut d’Investigació Biomèdica de Girona (IDIBGI), Salt, Spain. Departament de Ciències Mèdiques, Facultat de Medicina, Universitat de Girona, Girona, Spain, and Hospital Universitari de Girona Dr Josep Trueta

Subjects
primary progressive multiple sclerosis, Esclerosi múltiple, enfermedades del sistema nervioso::enfermedades autoinmunitarias del sistema nervioso::enfermedades autoinmunes desmielinizantes del SNC::esclerosis múltiple::esclerosis múltiple crónica progresiva [ENFERMEDADES], brain volume, Audiology, Esclerosi múltiple -- Tractament, Cohort Studies, Behavioral Neuroscience, 0302 clinical medicine, Cognition, fenómenos psicológicos::procesos mentales::cognición [PSIQUIATRÍA Y PSICOLOGÍA], magnetic resonance imaging, Prospective Studies, Gray Matter, Cervell, Original Research, medicine.diagnostic_test, 05 social sciences, Psychological Phenomena::Mental Processes::Cognition [PSYCHIATRY AND PSYCHOLOGY], Brain, brain volume, cognitive function, disability progression, magnetic resonance imaging, primary progressive multiple sclerosis, Multiple Sclerosis, Chronic Progressive, Magnetic Resonance Imaging, Straight gyrus, medicine.anatomical_structure, disability progression, Brain size, medicine.medical_specialty, Multiple Sclerosis, 050105 experimental psychology, lcsh:RC321-571, White matter, 03 medical and health sciences, Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Imaging::Tomography::Magnetic Resonance Imaging [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis::Multiple Sclerosis, Chronic Progressive [DISEASES], medicine, Humans, 0501 psychology and cognitive sciences, diagnóstico::técnicas y procedimientos diagnósticos::diagnóstico por imagen::tomografía::imagen por resonancia magnética [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Effects of sleep deprivation on cognitive performance, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, cognitive function, business.industry, Magnetic resonance imaging, Lobe, Cerebellar tonsil, Imatgeria per ressonància magnètica, business, 030217 neurology & neurosurgery, Multiple sclerosis -- Treatment
Abstract

Background and purpose Evidence on regional changes resulting from neurodegenerative processes underlying primary progressive multiple sclerosis (PPMS) is still limited. We assessed brain region volumes and their relationship with disability progression and cognitive function in PPMS patients. Methods This was an MRI analysis of 43 patients from the prospective Understanding Primary Progressive Multiple Sclerosis (UPPMS) cohort study. MRI scans were performed within 3 months before enrollment and at month 12. Results Gray matter volume of declive and white matter volumes adjacent to left straight gyrus, right calcarine sulcus, and right inferior occipital gyrus significantly decreased from baseline to month 12. Baseline white matter volumes adjacent to right amygdala and left cuneus significantly differed between patients with and without disability progression, as well as baseline gray matter volumes of left cuneus, right parahippocampal gyrus, right insula, left superior frontal gyrus, declive, right inferior temporal gyrus, right superior temporal gyrus (pole), and right calcarine sulcus. Baseline gray matter volumes of right cuneus and right superior temporal gyrus positively correlated with 12‐month Selective Reminding Test and Word List Generation performance, respectively. Gray matter changes in right superior semilunar lobe and white matter adjacent to left declive and right cerebellar tonsil also positively correlated with Word List Generation scores, while white matter change in left inferior semilunar lobe positively correlated with Symbol Digit Modalities Test performance after 12 months. Conclusions White and gray matter volumes of specific brain regions could predict disability progression and cognitive performance of PPMS patients after one year., The data described in the present manuscript provide a detailed description of region volume changes exhibited by primary progressive multiple sclerosis patients over one year, including decreases in gray matter declive and white matter adjacent to left straight gyrus, right calcarine sulcus, and right inferior occipital gyrus. In addition, baseline volumes of white matter adjacent to right amygdala and left cuneus could also predict 1‐year disability progression in patients with primary progressive multiple sclerosis, as well as baseline grey matter volumes of left cuneus, right parahippocampal gyrus, right insula, left superior frontal gyrus, declive, right inferior temporal gyrus, right superior temporal gyrus (pole), and right calcarine sulcus. Furthermore, baseline volumes of certain regions such as grey matter of right cuneus and right superior temporal gyrus could also predict cognitive performance after one year, as well as volume changes in grey matter of right superior semilunar lobe and white matter of left inferior semilunar lobe and adjacent to left declive and right cerebellar tonsil were correlates of cognitive performance.

Published
2021

19. Post-transplant cyclophosphamide containing regimens after matched sibling, matched unrelated and haploidentical donor transplants in patients with acute lymphoblastic leukemia in first complete remission, a comparative study of the ALWP of the EBMT

Author

Yener Koc, Jaime Sanz, Johanna Tischer, Emanuele Angelucci, Montserrat Rovira, Mahmoud Aljurf, Arnon Nagler, Annalisa Ruggeri, Nicolaus Kröger, Myriam Labopin, Bipin N. Savani, J. L. Diez-Martin, Fabio Ciceri, Jacques Emmanuel Galimard, Simona Sica, Mutlu Arat, Mohamad Mohty, Moiseev Ivan Sergeevich, Boris V. Afanasyev, Sanz, J., Galimard, J. -E., Labopin, M., Afanasyev, B., Sergeevich, M. I., Angelucci, E., Kroger, N., Koc, Y., Ciceri, F., Diez-Martin, J. L., Arat, M., Sica, S., Rovira, M., Aljurf, M., Tischer, J., Savani, B., Ruggeri, A., Nagler, A., Mohty, M., Hospital Universitari i Politècnic La Fe, Instituto de Salud Carlos III [Madrid] (ISC), 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], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'Hématologie et d'Immunologie [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), Pavlov First Saint Petersburg State Medical University [St. Petersburg], Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), University Hospital Hamburg-Eppendorf, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Medicana International [Istanbul, Turkey], Ospedale San Raffaele, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Sisli Florence Nightingale Hospital [Istanbul, Turkey], Università cattolica del Sacro Cuore [Roma] (Unicatt), King Faisal University (KFU), University-Hospital Munich-Großhadern [München], Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], and The Chaim Sheba Medical Center [Tel Hashomer, Israel]

Subjects
Male, Cancer Research, medicine.medical_treatment, Lymphoblastic Leukemia, Graft vs Host Disease, Hematopoietic stem cell transplantation, Acute lymphoblastic leukemia, 0302 clinical medicine, Cumulative incidence, RC254-282, Hematology, Hematopoietic Stem Cell Transplantation, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma, 3. Good health, Allogeneic stem cell transplant, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Cohort, Female, Post-transplant cyclophosphamide, medicine.drug, Adult, medicine.medical_specialty, Cyclophosphamide, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Young Adult, Internal medicine, medicine, Humans, Transplantation, Homologous, In patient, Diseases of the blood and blood-forming organs, Sibling, Molecular Biology, Antineoplastic Agents, Alkylating, Aged, Retrospective Studies, Alternative donor transplants, Haploidentical transplant, business.industry, Research, Transplantation, Haploidentical, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, RC633-647.5, business, 030215 immunology
Abstract

Background There is no information on the impact of donor type in allogeneic hematopoietic stem cell transplantation (HCT) using homogeneous graft-versus-host (GVHD) prophylaxis with post-transplant cyclophosphamide (PTCy) in acute lymphoblastic leukemia (ALL). Methods We retrospectively analyzed outcomes of adult patients with ALL in CR1 that had received HCT with PTCy as GVHD prophylaxis from HLA-matched sibling (MSD) (n = 78), matched unrelated (MUD) (n = 94) and haploidentical family (Haplo) (n = 297) donors registered in the EBMT database between 2010 and 2018. The median follow-up period of the entire cohort was 2.2 years. Results Median age of patients was 38 years (range 18–76). Compared to MSD and MUD, Haplo patients received peripheral blood less frequently. For Haplo, MUD, and MSD, the cumulative incidence of 100-day acute GVHD grade II–IV and III–IV, and 2-year chronic and extensive chronic GVHD were 32%, 41%, and 34% (p = 0.4); 13%, 15%, and 15% (p = 0.8); 35%, 50%, and 42% (p = 0.01); and 11%, 17%, and 21% (p = 0.2), respectively. At 2 years, the cumulative incidence of relapse and non-relapse mortality was 20%, 20%, and 28% (p = 0.8); and 21%, 18%, and 21% (p = 0.8) for Haplo, MUD, and MSD, respectively. The leukemia-free survival, overall survival and GVHD-free, relapse-free survival for Haplo, MUD, and MSD was 59%, 62%, and 51% (p = 0.8); 66%, 69%, and 62% (p = 0.8); and 46%, 44%, and 35% (p = 0.9), respectively. On multivariable analysis, transplant outcomes did not differ significantly between donor types. TBI-based conditioning was associated with better LFS. Conclusions Donor type did not significantly affect transplant outcome in patient with ALL receiving SCT with PTCy.

Published
2021

20. First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial

Author

Pierre-Jean Souquet, David P. Carbone, Michael Schenker, Shun Lu, S. Meadows-Shropshire, A. Alexandru, Pamela Salman, Hiroshi Sakai, Jaafar Bennouna, Maurice Pérol, Enriqueta Felip, Alejo Lingua, J. Yan, Juliana Janoski de Menezes, B. Zurawski, Martin Reck, Arnaud Scherpereel, C. Martin, Eduardo Richardet, Abderrahim Oukessou, Tudor-Eliade Ciuleanu, Manuel Cobo, O. Juan-Vidal, Pedro Rafael Martins De Marchi, Thomas John, Luis Paz-Ares, Shruti Agrawal, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), The Oncology Institute 'Prof. Dr. Ion Chiricuţă' [Cluj-Napoca, Romania] (TOI), Instituto de Investigación Biomédica [Malaga, Spain] (IBIMA), SF Nectarie Oncology Center [Craiova, Romania], Ambulatorium Chemioterapii [Bydgoszcz, Poland] (AC), Hospital Nossa Senhora Da Conceição [Porto Alegre, Brazil] (HNSDC), Instituto Oncológico De Córdoba [Córdoba, Argentina] (IODC), Immunogenic Cell Death and Mesothelioma Therapy (CRCINA-ÉQUIPE 4), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Centre hospitalier universitaire de Nantes (CHU Nantes), Vall d'Hebron Institute of Oncology [Barcelone] (VHIO), Vall d'Hebron University Hospital [Barcelona], Hospital Universitario La Fe [Valencia, Spain] (HU), Oncology Institute of Bucharest Professor Doctor Alexandru Trestioreanu [Bucharest, Romania] (OIB), Saitama Cancer Center [Saitama, Japan] (S2C), Instituto Medico Rio Cuarto SA [Córdoba, Argentina] (IMRC), Fundacion Arturo Lopez Perez [Santiago, Metropolitana, Chile] (FALP), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Barretos Cancer Hospital [São Paulo, Brazil], Instituto Alexander Fleming [Buenos Aires, Argentina] (IAF), Centre Léon Bérard [Lyon], Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 (ONCO-THAI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), University of Lille, CHU Lille, Shanghai Jiao Tong University [Shanghai], Austin Hospital [Melbourne], Austin Health, Ohio State University [Columbus] (OSU), Bristol-Myers Squibb [Princeton], German Center for Lung Research, Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, and Bernardo, Elizabeth

Subjects
Male, medicine.medical_specialty, Ipilimumab, [SDV.CAN]Life Sciences [q-bio]/Cancer, Neutropenia, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Carcinoma, Non-Small-Cell Lung, Antineoplastic Combined Chemotherapy Protocols, medicine, Clinical endpoint, Humans, 030212 general & internal medicine, Aged, Neoplasm Staging, business.industry, Hazard ratio, Middle Aged, medicine.disease, Interim analysis, 3. Good health, respiratory tract diseases, Regimen, Nivolumab, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Female, Neoplasm Recurrence, Local, business, Febrile neutropenia, medicine.drug
Abstract

Erratum in Correction to Lancet Oncol 2021; 22: 198-211. [No authors listed] Lancet Oncol. 2021 Mar;22(3):e92. doi: 10.1016/S1470-2045(21)00082-6. PMID: 33662299 No abstract available.; International audience; Background: First-line nivolumab plus ipilimumab has shown improved overall survival in patients with advanced non-small-cell lung cancer (NSCLC). We aimed to investigate whether the addition of a limited course (two cycles) of chemotherapy to this combination would further enhance the clinical benefit.Methods: This randomised, open-label, phase 3 trial was done at 103 hospitals in 19 countries. Eligible patients were aged 18 years or older with treatment-naive, histologically confirmed stage IV or recurrent NSCLC, and an Eastern Cooperative Oncology Group performance status of 0-1. Patients were randomly assigned (1:1) by an interactive web response system via permuted blocks (block size of four) to nivolumab (360 mg intravenously every 3 weeks) plus ipilimumab (1 mg/kg intravenously every 6 weeks) combined with histology-based, platinum doublet chemotherapy (intravenously every 3 weeks for two cycles; experimental group), or chemotherapy alone (every 3 weeks for four cycles; control group). Randomisation was stratified by tumour histology, sex, and PD-L1 expression. The primary endpoint was overall survival in all randomly assigned patients. Safety was analysed in all treated patients. Results reported here are from a pre-planned interim analysis (when the study met its primary endpoint) and an exploratory longer-term follow-up analysis. This study is active but no longer recruiting patients, and is registered with ClinicalTrials.gov, number NCT03215706.Findings: Between Aug 24, 2017, and Jan 30, 2019, 1150 patients were enrolled and 719 (62·5%) randomly assigned to nivolumab plus ipilimumab with two cycles of chemotherapy (n=361 [50%]) or four cycles of chemotherapy alone (n=358 [50%]). At the pre-planned interim analysis (median follow-up 9·7 months [IQR 6·4-12·8]), overall survival in all randomly assigned patients was significantly longer in the experimental group than in the control group (median 14·1 months [95% CI 13·2-16·2] vs 10·7 months [9·5-12·4]; hazard ratio [HR] 0·69 [96·71% CI 0·55-0·87]; p=0·00065). With 3·5 months longer median follow-up (median 13·2 months [IQR 6·4-17·0]), median overall survival was 15·6 months (95% CI 13·9-20·0) in the experimental group versus 10·9 months (9·5-12·6) in the control group (HR 0·66 [95% CI 0·55-0·80]). The most common grade 3-4 treatment-related adverse events were neutropenia (in 24 [7%] patients in the experimental group vs 32 [9%] in the control group), anaemia (21 [6%] vs 50 [14%]), diarrhoea (14 [4%] vs two [1%]), increased lipase (22 [6%] vs three [1%]), and asthenia (tjree [1%] vs eight [2%]). Serious treatment-related adverse events of any grade occurred in 106 (30%) patients in the experimental group and 62 (18%) in the control group. Seven (2%) deaths in the experimental group (acute kidney failure, diarrhoea, hepatotoxicity, hepatitis, pneumonitis, sepsis with acute renal insufficiency, and thrombocytopenia; one patient each) and six (2%) deaths in the control group (anaemia, febrile neutropenia, pancytopenia, pulmonary sepsis, respiratory failure, and sepsis; one patient each) were treatment related.Interpretation: Nivolumab plus ipilimumab with two cycles of chemotherapy provided a significant improvement in overall survival versus chemotherapy alone and had a favourable risk-benefit profile. These data support this regimen as a new first-line treatment option for patients with advanced NSCLC.Funding: Bristol Myers Squibb.

Published
2021

21. Echocardiographic Left Ventricular Mass Estimation: Two-Dimensional Area-Length Method is Superior to M-Mode Linear Method in Swine Models of Cardiac Diseases

Author

Jaume Aguero, Roger J. Hajjar, Kelly P. Yamada, Kenneth Fish, Koichi Nomoto, Taro Kariya, Satoshi Miyashita, Shin Watanabe, Kiyotake Ishikawa, Nadjib Hammoudi, Olympia Bikou, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Actions for OnCogenesis understanding and Target Identification in ONcology (ACTION), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Centro Nacional de Investigaciones Cardiovasculares Carlos III [Madrid, Spain] (CNIC), Instituto de Salud Carlos III [Madrid] (ISC), Hospital Universitari i Politècnic La Fe, and Phospholamban Foundation

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, Sus scrofa, Population, Myocardial Infarction, Pharmaceutical Science, Infarction, 030204 cardiovascular system & hematology, Linear methods, Ventricular Function, Left, Article, Muscle hypertrophy, Left ventricular mass, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, Internal medicine, Genetics, Animals, Medicine, In patient, education, Genetics (clinical), Observer Variation, education.field_of_study, Ventricular Remodeling, business.industry, Reproducibility of Results, medicine.disease, Disease Models, Animal, Area length method, 030104 developmental biology, Linear relationship, Echocardiography, Cardiology, Molecular Medicine, Female, Hypertrophy, Left Ventricular, Cardiology and Cardiovascular Medicine, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Echocardiography offers rapid and cost-effective estimations of left ventricular (LV) mass, but its accuracy in patients with cardiac disease remains unclear. LV mass was measured by M-mode-based linear method and two-dimensional echocardiography (2DE)-based area-length method in pig models and correlation with actual LV weight was assessed. Twenty-six normal, 195 ischemic heart disease (IHD), and 33 non-IHD HF pigs were included. A strong positive linear relationship to the actual LV weight was found with 2DE-based area-length method (r = 0.82, p

Published
2020

22. Bronchoscopist's perception of the quality of the single-use bronchoscope (Ambu aScope4™) in selected bronchoscopies: a multicenter study in 21 Spanish pulmonology services

Author

Flandes, Javier, Giraldo-Cadavid, Luís Fernando, Alfayate, Javier, Fernández-Navamuel, Iker, Agusti, Carlos, Lucena, Carmen M., Rosell, Antoni, Andreo, Felipe, Centeno, Carmen, Montero, C., Vidal, Iria, García-Alfonso, Lucía, Bango, Antonio, Ariza, Miguel, Gallego, Rocío, Orta, Marta, Bello, Salvador, Mincholé, Elisa, Torrego, Alfons, Pajares, Virginia, González, Héctor, Wangüemert, Aurelio Luís, Pérez-Izquierdo, Julio, Disdier, Carlos, de Vega Sanchez, Blanca, Cordovilla, Rosa, Cascón, Juan, Cruz, Antonio, García-López, J.Javier, Puente, Luis, Benedetti, Paola, García-Gallo, Cristina L., Díaz Nuevo, Gema, Aguado, Silvia, Partida, Concepción, Díaz-Agero, Prudencio, Luque Crespo, Estefania, Pavón, María, Páez, Francisco, Cases, Eenrique, Martínez, Raquel, Briones, Andrés, Fernández, Cleofe, Martín Serrano, Concepción, Uribe-Hernández, Ana María, Robles, Jose, Universitat Autònoma de Barcelona, [Flandes,J, Alfayate,J, Fernández‑Navamuel,I] Pneumology Service, Bronchoscopy and Interventional Pulmonology Unit, University Hospital 'Fundación Jiménez Díaz', ISS-FJD CIBERES, Madrid, Spain.[Giraldo‑Cadavid,LF] Interventional Pulmonology, Fundación Neumológica Colombiana, Profesor Titular Universidad de La Sabana, Bogotá, DC, Colombia. [Agusti,C, Lucena,CM] Department of Epidemiology and Biostatistics, School of Medicine, Universidad de La Sabana, La Caro, Chía, Colombia. [Rosell,A] Pneumology Service, Hospital Clínic Universitari, Barcelona, Spain. [Andreo,F, Centeno,C] Pneumology Service, Hospital Universitari de Bellvitge, Barcelona, Spain. [Montero,C, Vidal,I, García-Alfonso,L] Pneumology Service, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain. [Bango,A, Ariza,M] Pulmonology Service, Complexo Hospitalario Universitario, A Coruña, Spain. [Gallego,R, Orta,M] Pneumology Service, Central University Hospital of Asturias, Oviedo Asturias, Spain. [Bello,S, incholé,E] Pneumology Service, Hospital San Pedro de Alcántara, Cáceres, Spain. [Torrego, Pajares,V] Pneumology Service, Miguel Servet University Hospital, Zaragoza, Spain. [González,H] Pneumology Service, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. [Wangüemert,AL] Pneumology Service, University Hospital of the Canary Islands, Santa Cruz de Tenerife, Spain. [Pérez‑Izquierdo,J] Pneumology Service, Hospital San Juan de Dios, Santa Cruz de Tenerife, Spain. [Disdier,C, de Vega Sanchez,B] Pneumology Service, Galdakao University Hospital, Bilbao Vizcaya, Spain. [Cordovilla,R, Cascón,J, Cruz,A] Pneumology Service, Hospital Clínico Universitario, Valladolid, Spain. [García‑López,JJ, Puente,L, Benedetti,P] Pneumology Service, University Assistance Complex, Salamanca, Spain. [García‑Gallo,CL, Díaz Nuevo,G, Aguado,G] Pneumology Service, Hospital Universitario Gregorio Marañón, Madrid, Spain. [Partida,C, Díaz‑Agero,P]Pneumology Service, Puerta de Hierro University Hospital, Madrid, Spain. [Luque Crespo,E, Pavón,M]Thoracic Surgery Service, Hospital Universitario La Paz, Madrid, Spain. [Páez,F] Pneumology Service, Virgen de Macarena University Hospital, Seville, Spain. [Cases,E, Martínez,R, Briones,A] Pneumology Service, Carlos Hay Regional University Hospital, Malaga, Spain. [Fernández,C, and Martín Serrano,C] Respiratory Endoscopy Unit, Hospital Universitari i Politècnic La Fe, Valencia, Spain. [Uribe‑Hernández,AM] Pneumology Service, General University Hospital, Alicante, Spain. [Robles,J] Fundación Neumológica Colombiana, Bogotá, DC, Colombia. [Giraldo‑Cadavid,LF] Industrial Electronic Engineering, GHS SL, Madrid, Spain.

Subjects
Bronchoscopist, Health Knowledge, Attitudes, Practice, aScope4™, CUSUM, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Bronchoscopy, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Equipment Design [Medical Subject Headings], Broncoscòpia, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Attitude::Attitude to Health::Health Knowledge, Attitudes, Practice [Medical Subject Headings], Medicine, 030212 general & internal medicine, Prospective Studies, aScope4&#8482, Disposable Equipment, media_common, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Thoracic Surgical Procedures::Pulmonary Surgical Procedures::Bronchoscopy [Medical Subject Headings], medicine.diagnostic_test, Equipment Design, Quality, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cross-Sectional Studies [Medical Subject Headings], Pulmonology, Bronchoscopes, Pulmonologists, Clinical Competence, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Equipment and Supplies::Disposable Equipment [Medical Subject Headings], Learning Curve, Bronchoalveolar lavage, medicine.medical_specialty, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], Attitude of Health Personnel, media_common.quotation_subject, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Analytical, Diagnostic and Therapeutic Techniques and Equipment::Equipment and Supplies::Diagnostic Equipment::Endoscopes::Bronchoscopes [Medical Subject Headings], Bronchoscopies, CUSUM analysis, 03 medical and health sciences, Internal medicine, Humans, Quality (business), Medical physics, lcsh:RC705-779, Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings], business.industry, SARS-CoV-2, Research, COVID-19, lcsh:Diseases of the respiratory system, Cross-Sectional Studies, 030228 respiratory system, Multicenter study, Spain, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Health Care Surveys [Medical Subject Headings], Health Care Surveys, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Attitude::Attitude of Health Personnel [Medical Subject Headings], Health Care::Health Services Administration::Quality of Health Care::Clinical Competence [Medical Subject Headings], business, Psychiatry and Psychology::Psychological Phenomena and Processes::Psychology, Applied::Psychology, Educational::Learning::Learning Curve [Medical Subject Headings]
Abstract

Background The disposable bronchoscope is an excellent alternative to face the problem of SARS-CoV-2 and other cross infections, but the bronchoscopist's perception of its quality has not been evaluated. Methods To evaluate the quality of the Ambu-aScope4 disposable bronchoscope, we carried out a cross-sectional study in 21 Spanish pulmonology services. We use a standardized questionnaire completed by the bronchoscopists at the end of each bronchoscopy. The variables were described with absolute and relative frequencies, measures of central tendency and dispersion depending on their nature. The existence of learning curves was evaluated by CUSUM analysis. Results The most frequent indications in 300 included bronchoscopies was bronchial aspiration in 69.3% and the median duration of these was 9.1 min. The route of entry was nasal in 47.2% and oral in 34.1%. The average score for ease of use, image, and aspiration quality was 80/100. All the planned techniques were performed in 94.9% and the bronchoscopist was satisfied in 96.6% of the bronchoscopies. They highlighted the portability and immediacy of the aScope4TM to start the procedure in 99.3%, the possibility of taking and storing images in 99.3%. The CUSUM analysis showed average scores > 70/100 from the first procedure and from the 9th procedure more than 80% of the scores exceeded the 80/100 score. Conclusions The aScope4™ scored well for ease of use, imaging, and aspiration. We found a learning curve with excellent scores from the 9th procedure. Bronchoscopists highlighted its portability, immediacy of use and the possibility of taking and storing images.

Published
2020

23. Management of chronic liver disease-associated severe thrombocytopenia in Spain: a view from the experts

Author

Manuel Romero-Gómez, Alicia Gil Aguirre, José Luis Calleja-Panero, Raúl J. Andrade, Rafael Esteban, Maria Eva Mingot-Castellano, Rocío Muñoz-Peñín, Rafael Bañares, Javier Crespo, Roy Bentley, John Shepherd, Isidro Jarque, Shionogi, and [Calleja-Panero,JL] Department of Hepatology. Hospital Universitario Puerta de Hierro Majadahonda. Madrid, Spain. [Andrade,RJ] Digestive Diseases Clinical Management Unit. Instituto de Investigación Biomédica de Málaga-IBIMA. Hospital Universitario Virgen de la Victoria. Universidad de Málaga. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas CIBERehd. Málaga, Spain. [Bañares,J] Department of Hepatology. Hospital General Universitario Gregorio Marañón. Madrid, Spain. [Crespo,J] Department of Hepatology. Hospital Universitario Marqués de Valdecilla. Santander, Spain. [Esteban,R] Department of Hepatology. Hospital Universitario Vall d’Hebron. Barcelona, Spain. [Jarque,I] Department of Hematology. Hospital Universitari i Politècnic La Fe. Valencia, Spain. [Mingot-Castellano,EM] Department of Hematology. Hospital Universitario Virgen del Rocío. Sevilla, Spain. [Romero-Gómez,M] Department of Hepatology. Hospital Universitario Virgen del Rocío. Sevilla, Spain. [Muñoz-Peñín,R] Shionogi Inc. Madrid, Spain. [Bentley,R] Shionogi Inc. Florham Park. New Jersey, USA. [Gil,A] Omakase Consulting S.L. Barcelona, Spain.

Subjects
medicine.medical_specialty, Epidemiology, Terapéutica, MEDLINE, Delphi method, Platelet Transfusion, Lung injury, Chronic liver disease, Técnica Delfos, Delphi, Thrombo-poietin receptor agonists, Thrombopoietin receptor agonists, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Health care, medicine, Epidemiología, Humans, Intensive care medicine, Adverse effect, Platelet transfusion, Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings], business.industry, Transfusión de plaquetas, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Biological Therapy::Blood Transfusion::Blood Component Transfusion::Platelet Transfusion [Medical Subject Headings], Liver Diseases, Gastroenterology, Anemia, General Medicine, Diseases::Hemic and Lymphatic Diseases::Hematologic Diseases::Blood Platelet Disorders::Thrombocytopenia [Medical Subject Headings], medicine.disease, Trombocitopenia, Thrombocytopenia, Severe thrombocytopenia, Treatment, Plate-let transfusion, Diseases::Digestive System Diseases::Liver Diseases [Medical Subject Headings], Spain, business, Diseases::Hemic and Lymphatic Diseases::Hematologic Diseases::Anemia [Medical Subject Headings]
Abstract

[Background] chronic liver disease (CLD) patients often present thrombocytopenia (TCP) and when severe, it may prevent them from undergoing necessary invasive procedures due to an increased bleeding risk. The lack of scientific evidence makes it impossible to determine key aspects of the current management and associated healthcare burden of these patients in Spain., [Purpose] to gain insight into the current situation of patients with CLD-associated severe TCP undergoing invasive procedures in Spain, based on the experience of clinical experts. Methods: national Delphi study involving 32 medical experts., [Results] the estimated prevalence of CLD-associated severe TCP is approximately 5,967, with an annual incidence of 1,148 new patients. Patients undergo a median of 1 (0-3) invasive procedures/year. Platelet transfusions (PTs) are the standard option to raise platelet counts and are associated with significant burden. The achievement of target platelet levels (≥ 50 x 109/l) after a transfusion is not routinely measured. The lack of effectiveness and short life span of transfused platelets can lead to procedure cancellations and bleeding events, which potentially affect patient outcomes. Adverse events occur in 1-25 % of patients, including mild (febrile and allergic reactions) and severe events (e.g., transfusion-related acute lung injury). Between 5-15 % of patients are unfit to receive PTs and approximately 3 % are treated off-label with thrombopoietin receptor agonists., [Conclusions] this study provides a snapshot of the current situation in Spain, highlighting that the current management is poorly standardized and suboptimal in some cases. The results suggest the benefit of developing a consensus document to address some of these shortcomings and to advance in the search for alternatives to PTs., This study was funded by Shionogi Inc.

Published
2020

24. A pediatric regimen for adolescents and young adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: Results of the ALLRE08 PETHEMA trial

Author

Ribera, Josep Maria, Morgades, Mireia, Montesinos, Pau, Tormo, Mar, Martínez Carballeira, Daniel, González Campos, José, Gil, Cristina, Barba, Pere, García Boyero, Raimundo, Coll, Rosa, Pedreño, María, Ribera, Jordi, Mercadal, Santiago, Vives, Susana, Novo, Andrés, Genescà, Eulàlia, Hernández Rivas, Jesús María, Bergua, Juan, Amigo, María Luz, Vall Llovera, Ferran, Martínez Sánchez, Pilar, Calbacho, María, García Cadenas, Irene, Garcia Guiñon, Antonio, Sánchez Sánchez, María José, Cervera, Marta, Feliu, Evarist, Orfao, Alberto, PETHEMA Group, Josep Carreras Leukemia Foundation, Universidad Autónoma de Barcelona, CSIC-USAL - Instituto de Biología Molecular y Celular del Cancer de Salamanca (IBMCC), Institut Català de la Salut, [Ribera JM, Morgades M] Departments of Clinical Hematology, ICO-Hospital Germans Trias i Pujol. Josep Carreras Research Institute, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Montesinos P] Departments of Clinical Hematology, Hospital Universitari i Politècnic La Fe, CIBERONC, Instituto Carlos III, Valencia, Spain, Madrid, Spain. [Tormo M] Departments of Clinical Hematology, Hospital Clínico Valencia, Valencia, Spain. [Martínez-Carballeira D] Hospital Central de Asturias, Oviedo, Spain. [González-Campos J] Departments of Clinical Hematology, Hospital Universitario Virgen del Rocío, Sevilla, Spain. [Barba P] Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Male, 0301 basic medicine, Cancer Research, Neoplasm, Residual, Lymphoblastic Leukemia, Adolescents, 0302 clinical medicine, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, neoplasias::neoplasias por tipo histológico::leucemia::leucemia linfoide::leucemia-linfoma linfoblástico de células precursoras [ENFERMEDADES], Medicine, Philadelphia Chromosome, Cumulative incidence, Other subheadings::/therapeutic use [Other subheadings], Young adult, Complete response, health care economics and organizations, Original Research, Clinical Trials as Topic, Remission Induction, terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], hemic and immune systems, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Prognosis, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, humanities, Survival Rate, Oncology, 030220 oncology & carcinogenesis, behavior and behavior mechanisms, Female, Adult, acute lymphoblastic leukemia, adolescents and young adults, pediatric treatment, medicine.medical_specialty, Adolescent, Philadelphia Chromosome Negative, education, acute lymphoblastic leukemia, lcsh:RC254-282, Teenagers, Young Adult, 03 medical and health sciences, Internal medicine, Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Overall survival, Humans, Radiology, Nuclear Medicine and imaging, In patient, Leucèmia limfocítica crònica, Neoplasms::Neoplasms by Histologic Type::Leukemia::Leukemia, Lymphoid::Precursor Cell Lymphoblastic Leukemia-Lymphoma [DISEASES], business.industry, Otros calificadores::/uso terapéutico [Otros calificadores], Clinical Cancer Research, social sciences, personas::Grupos de Edad::adolescente [DENOMINACIONES DE GRUPOS], Persons::Age Groups::Adolescent [NAMED GROUPS], Regimen, 030104 developmental biology, Leucèmia limfoblàstica - Quimioteràpia, pediatric treatment, Chronic lymphocytic leukemia, Neoplasm Recurrence, Local, business, adolescents and young adults, Follow-Up Studies
Abstract

On behalf of the PETHEMA Group, Spanish Society of Hematology., [Background]: Pediatric‐based or ‐inspired trials have improved the prognosis of adolescents and young adults (AYA) with Philadelphia chromosome‐negative (Ph‐neg) acute lymphoblastic leukemia (ALL)., [Methods]: This study reports the results of treatment of the ALLRE08 trial, a full pediatric trial for AYA aged 15‐30 years with standard‐risk (SR) ALL., [Results]: From 2008 to 2018, 89 patients (38 adolescents [15‐18 years] and 51 young adults [YA, 19‐30 years], median age: 20 [15‐29] years) were enrolled in the ALLRE08 trial. The complete response (CR) was 95%. Twenty‐two patients were transferred to a high‐risk (HR) protocol because of poor marrow response on day 14 (n = 20) or high‐level of end‐induction minimal residual response (MRD ≥ 0.25%, n = 2). Cumulative incidence of relapse (CIR) at 5 years was 35% (95%CI: 23%‐47%), with significant differences between adolescents and YA: 13% (4%‐28%) vs 52% (34%‐67%), P = .012. No treatment‐related mortality was observed in 66/66 patients following the ALLRE08 trial vs 3/23 patients moved to a HR trial. The estimated 5‐year overall survival (OS) was 74% (95%CI: 63%‐85%), with significantly higher rates for adolescents vs YA: 87% (95%CI: 74%‐100%) vs 63% (46%‐80%), P = .021. Although CIR or OS were lower in patients who were transferred to a HR trial, the differences were not statistically significant (CIR: 34% [21%‐47%] vs 37% [14%‐61%]; OS: 78% [66%‐90%] vs 61% [31%;91%])., [Conclusion]: A full pediatric trial is feasible and effective for AYA with Ph‐neg, SR‐ALL, with better results for adolescents than for YA. Outcome of patients with poor early response rescued with a HR trial was not significantly inferior., We thanks to the following institutions from Spain their support for this paper: ICO‐Hospital Germans Trias i Pujol. Josep Carreras Research Institute. Universitat Autònoma de Barcelona. Hospital Universitari i Politècnic La Fe, Valencia. Hospital Clínico Valencia. Hospital Central de Asturias, Oviedo. Hospital Universitario Virgen del Rocío, Sevilla. Hospital General Universitario de Alicante. Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona. Hospital General Universitario de Castellón. ICO‐Hospital Josep Trueta, Girona. Hospital Dr Peset, Valencia. ICO‐Hospital Duran i Reynals, L'Hospitalet de Llobregat. Hospital Son Espases, Palma de Mallorca. Hospital Clínico Universitario, Cancer Research Center (IBMCC‐CSIC/USAL), Cytometry Service, Salamanca. Hospital San Pedro de Alcántara, Cáceres. Hospital Morales Meseguer, Murcia. Hospital Mútua de Terrassa, Terrassa. Hospital Doce de Octubre, Madrid. Hospital Ramón y Cajal, Madrid. Hospital de Sant Pau, Barcelona. Hospital Arnau de Vilanova, Lleida. Hospital Lucus Augusti, Lugo. ICO‐Hospital Joan XXIII, Tarragona.

Published
2020

25. Clinical characteristics of patients with central nervous system relapse in BCR-ABL1-positive acute lymphoblastic leukemia: the importance of characterizing ABL1 mutations in cerebrospinal fluid

Author

Ma José Moreno, Lourdes Escoda, Pau Montesinos, María Pilar Martínez, Ricardo Sanchez, Teresa Bernal, Joaquin Martinez-Lopez, Eugenia Abella, Pilar Bravo, Jesús María Hernández-Rivas, José González-Campos, Olga García, Rafael Alberto Alonso, Jordi Ribera, Sònia Piernas, Santiago Mercadal, Rodrigo Martino, Pere Barba, Antoni Garcia-Guiñon, Cristina Gil, Ramon Guardia, José-María Ribera, Ma Luz Amigo, José María Sánchez-Pina, Manuel Barrios, Rosa Ayala, Esperanza Lavilla, [Sanchez,R, Ayala,R, Alonso,RA, Martínez,MP, Sanchez-Pina, Martínez-López,J] Instituto de Investigación Hospital 12 de Octubre (i+12), Servicio de Hematología, Hematología Traslacional, Hospital Universitario 12 de Octubre, Spain. [Ribera,J, García,O, Ribera,JM] Institut de Recerca contra la Leucèmia Josep Carreras, ICO-Hospital Germans Trias i Pujol, Badalona, Spain. [Mercadal,S] ICO-Hospital Duran i Reynals (Bellvitge), Barcelona, Spain. [Montesinos,P] Hospital Universitari i Politècnic La Fe, Valencia, Spain. [Martino,R] Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. [Barba,P] Hospital Universitari Vall d’Hebron, Barcelona, Spain. [González-Campos,J] Hospital Universitario Virgen del Rocío, Sevilla, Spain. [Barrios,M] Hospital Regional Universitario Carlos Haya, Málaga, Spain. [Lavilla,E] Hospital Universitario Lucus Augusti, Lugo, Spain. [Gil,C] Hospital General Universitario de Alicante, Alicante, Spain. [Bernal,T] Hospital Universitario Central de Asturias, Oviedo, Spain. [Escoda,L] Hospital Universitari Joan XXIII, Tarragona, Spain. [Abella,E] Hospital del Mar, Barcelona, Spain. [Amigo,ML] Hospital General Universitario Morales Meseguer, Murcia, Spain. [Moreno,MJ] Hospital Universitario Virgen de la Victoria, Málaga, Spain. [Bravo,P] Hospital de Fuenlabrada, Fuenlabrada, Madrid, Spain. [Guàrdia,R] ICO-Hospital Universitari Dr. Josep Trueta, Girona, Spain. [Hernández-Rivas,JM] Hospital Universitario de Salamanca, Salamanca, Spain. [García-Guiñón,A] Hospital Universitari Arnau de Vilanova, Lleida, Spain. [Piernas,S] Hospital Universitari Parc Taulí, Sabadell, Barcelona, Spain., Fundación CRIS contra el Cáncer, Instituto de Salud Carlos III, and Red Temática de Investigación Cooperativa en Cáncer (España)

Subjects
Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Recurrence [Medical Subject Headings], Central Nervous System, Male, Models, Molecular, 0301 basic medicine, Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::DNA::DNA, Single-Stranded::DNA, Complementary [Medical Subject Headings], Fusion Proteins, bcr-abl, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Sequence Analysis::High-Throughput Nucleotide Sequencing [Medical Subject Headings], Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Neoplasm Proteins::Oncogene Proteins::Proto-Oncogene Proteins::Proto-Oncogene Proteins c-bcr [Medical Subject Headings], Kaplan-Meier Estimate, medicine.disease_cause, Somatic evolution in cancer, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Proteínas proto-oncogénicas c-bcr, Cerebrospinal fluid, Recurrence, hemic and lymphatic diseases, Outcome Assessment, Health Care, Acute lymphoblastic leukemia relapse, Proto-Oncogene Proteins c-abl, Aged, 80 and over, Mutation, ABL, Hematology, Médula ósea, High-Throughput Nucleotide Sequencing, General Medicine, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Humanos, Mutation analysis, medicine.anatomical_structure, Original Article, Female, Mesilato de imatinib, Leucemia-Linfoma linfoblástico de células precursoras, ADN complementario, Adult, medicine.medical_specialty, Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation [Medical Subject Headings], Evolución clonal, Secuenciación de nucleótidos de alto rendimiento, Central nervous system, Recurrencia, Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Clonal Evolution [Medical Subject Headings], Outcome Assessment (Health Care), 03 medical and health sciences, Internal medicine, Diseases::Neoplasms::Neoplasms by Histologic Type::Leukemia::Leukemia, Lymphoid::Precursor Cell Lymphoblastic Leukemia-Lymphoma [Medical Subject Headings], medicine, Humans, Aged, Sistema nerviós central, Mutación, Neoplasia, business.industry, Anatomy::Hemic and Immune Systems::Immune System::Bone Marrow [Medical Subject Headings], BCR-ABL1, Protein Structure, Tertiary, Clinical trial, Chemicals and Drugs::Organic Chemicals::Amides::Benzamides::Imatinib Mesylate [Medical Subject Headings], 030104 developmental biology, Leucèmia limfoblàstica, Immunology, Feasibility Studies, Bone marrow, business
Abstract

We investigated the frequency, predictors, and evolution of acute lymphoblastic leukemia (ALL) in patients with CNS relapse and introduced a novel method for studying BCR-ABL1 protein variants in cDNA from bone marrow (BM) and cerebrospinal fluid (CSF) blast cells. A total of 128 patients were analyzed in two PETHEMA clinical trials. All achieved complete remission after imatinib treatment. Of these, 30 (23%) experienced a relapse after achieving complete remission, and 13 (10%) had an isolated CNS relapse or combined CNS and BM relapses. We compared the characteristics of patients with and without CNS relapse and further analyzed CSF and BM samples from two of the 13 patients with CNS relapse. In both patients, classical sequencing analysis of the kinase domain of BCR-ABL1 from the cDNA of CSF blasts revealed the pathogenic variant p.L387M. We also performed ultra-deep next-generation sequencing (NGS) in three samples from one of the relapsed patients. We did not find the mutation in the BM sample, but we did find it in CSF blasts with 45% of reads at the time of relapse. These data demonstrate the feasibility of detecting BCR-ABL1 mutations in CSF blasts by NGS and highlight the importance of monitoring clonal evolution over time., This work was supported by the Fundación CRIS and Red Temática de Investigación Cooperativa en Cáncer (RTICC), Instituto de Salud Carlos III (Ref.: RD12/0036/0061 to JML).

Published
2017

26. Outcome of older (≥70 years) APL patients frontline treated with or without arsenic trioxide-an International Collaborative Study

Author

Pierre Fenaux, Ana Garrido, David Martínez-Cuadrón, Uwe Platzbecker, Gabriel Ghiaur, Olga Salamero, Javier de la Serna, Lionel Adès, Sabine Kayser, Norbert Vey, Richard F. Schlenk, Xavier Thomas, Eva Lengfelder, Pau Montesinos, Arnaud Pigneux, Ramy Rahmé, Agnès Guerci-Bresler, Miguel A. Sanz, Marta Sobas, Cristina Gil, Mar Tormo, Mark J. Levis, Emmanuel Raffoux, Institut Català de la Salut, [Kayser S] Medical Clinic and Policlinic I, Hematology and Cellular Therapy, University Hospital Leipzig, Leipzig, Germany. German Cancer Research Center (DKFZ), Heidelberg, Germany. Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany. [Rahmé R] Hôpital Saint Louis, Université Paris Diderot, Paris, France. [Martínez-Cuadrón D] Hematology Department, Hospital Universitari i Politècnic, La Fe, Avinguda Fernando Abril Martorell, 106, 46026 València, Spain. CIBERONC, Instituto Carlos III, Madrid, Spain. [Ghiaur G] Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA. [Thomas X] Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre Bénite, Lyon, France. [Sobas M] Department of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Wroclaw Medical University, Wroclaw, Poland. [Salamero O] Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Male, Cancer Research, ANTHRACYCLINE MONOCHEMOTHERAPY, Myeloid, medicine.medical_treatment, International Cooperation, ACUTE PROMYELOCYTIC LEUKEMIA, Leucèmia mieloide aguda - Quimioteràpia, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Gastroenterology, chemistry.chemical_compound, Remission induction, Arsenic Trioxide, Antineoplastic Combined Chemotherapy Protocols, Cumulative incidence, Arsenic trioxide, ELDERLY-PATIENTS, Aged, 80 and over, ADDITIONAL CHROMOSOME-ABNORMALITIES, Remission Induction, Neoplasms::Neoplasms by Histologic Type::Leukemia::Leukemia, Myeloid::Leukemia, Myeloid, Acute [DISEASES], Hematology, Leukemia, Leukemia, Myeloid, Acute, medicine.anatomical_structure, Treatment Outcome, Oncology, Female, FLT3 GENE, Acute promyelocytic leukemia, medicine.medical_specialty, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], ACUTE MYELOID-LEUKEMIA, Article, Acute myeloid leukaemia, neoplasias::neoplasias por tipo histológico::leucemia::leucemia mieloide::leucemia mieloide aguda [ENFERMEDADES], Internal medicine, White blood cell, medicine, Humans, Clinical genetics, neoplasms, CONSOLIDATION THERAPY, Aged, Chemotherapy, business.industry, organic chemicals, diagnóstico::pronóstico::resultado del tratamiento [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Correction, biochemical phenomena, metabolism, and nutrition, Diagnosis::Prognosis::Treatment Outcome [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], medicine.disease, TANDEM DUPLICATION, bacterial infections and mycoses, biological factors, RISK-ADAPTED TREATMENT, TRANS-RETINOIC ACID, chemistry, Avaluació de resultats (Assistència sanitària), business
Abstract

Data on outcome in older (≥70 years) patients with acute promyelocytic leukemia after treatment with arsenic trioxide (ATO) compared with standard chemotherapy (CTX) is scarce. We evaluated 433 patients (median age, 73.4 years) treated either with ATO+ all-trans retinoic acid (ATO/ATRA; n = 26), CTX/ATRA + ATO during consolidation (CTX/ATRA/ATO; n = 148), or with CTX/ATRA (n = 259). Median follow-up for overall survival (OS) was 4.8 years. Complete remissions (CR) were achieved in 92% with ATO/ATRA and 82% with CTX/ATRA; induction death rates were 8% and 18%, respectively. For analysis of postremission outcomes we combined the ATO/ATRA and CTX/ATRA/ATO groups (ATO/ATRA ± CTX). Cumulative incidence of relapse (CIR) was significantly lower after ATO/ATRA ± CTX compared with CTX/ATRA (P P = 0.20). High (>10 × 109/l) white blood cell (WBC) counts at diagnosis were associated with higher CIR (P P = 0.48). ATO, when added to ATRA or CTX/ATRA is feasible and effective in elderly patients for remission induction and consolidation, particularly in patients with high WBC at diagnosis.

Published
2019

27. Usefulness of Liquid Biopsy Biomarkers from Aqueous Humor in Predicting Anti-VEGF Response in Diabetic Macular Edema: Results of a Pilot Study

Author

Olga Simó-Servat, Laura Brianso-Llort, Rafael Simó, Cristina Hernández, Salvador Garcia-Delpech, Patricia Udaondo, [Udaondo P, García-Delpech S] Department of Ophthalmology, Hospital Universitari i Politècnic La Fe, Valencia, Spain. [Hernández C, Briansó-Llort L, Simó-Servat O, Simó R] Grup de Recerca en Diabetis i metabolisme, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ICSIII), Madrid, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Chemokine, VEGF receptors, lcsh:Medicine, Gastroenterology, 0302 clinical medicine, Diabetic macular edema, anti-vegf agents, 030212 general & internal medicine, Otros calificadores::Otros calificadores::/antagonistas & inhibidores [Otros calificadores], vegf, medicine.diagnostic_test, biology, General Medicine, personalized medicine, VEGF, Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Angiogenic Proteins::Vascular Endothelial Growth Factors [CHEMICALS AND DRUGS], aminoácidos, péptidos y proteínas::péptidos::péptidos y proteínas de señalización intercelular::proteínas angiogénicas::factores de crecimiento endotelial vascular [COMPUESTOS QUÍMICOS Y DROGAS], medicine.symptom, Biòpsia, diabetic macular edema, aqueous humor, Aqueous humor, medicine.medical_specialty, Other subheadings::Other subheadings::/antagonists & inhibitors [Other subheadings], Factors de creixement fibroblàstic, Inflammation, Article, 03 medical and health sciences, Internal medicine, Statistical significance, medicine, Eye Diseases::Retinal Diseases::Retinal Degeneration::Macular Degeneration::Macular Edema [DISEASES], Liquid biopsy, business.industry, oftalmopatías::enfermedades de la retina::degeneración retiniana::degeneración macular::edema macular [ENFERMEDADES], lcsh:R, biomarkers, técnicas de investigación::técnicas de laboratorio clínico::técnicas de investigación::técnicas de laboratorio clínico::manejo de muestras::biopsia::técnicas de investigación::biopsia líquida [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Anti-VEGF agents, Personalized medicine, inflammation, Immunoassay, Retinopatia diabètica, 030221 ophthalmology & optometry, biology.protein, Investigative Techniques::Clinical Laboratory Techniques::Investigative Techniques::Clinical Laboratory Techniques::Specimen Handling::Biopsy::Investigative Techniques::Liquid Biopsy [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], business, Biomarkers
Abstract

The objective was to investigate the usefulness of the &ldquo, liquid biopsy&rdquo, of aqueous humor (AH) to predict the clinical response after intravitreal injections (IVT) of anti-VEGF agents for treating diabetic macular edema (DME). For this purpose, AH samples obtained during the first anti-VEGF IVT from 31 type two diabetic patients were analyzed. Patients were classified into three groups according to their anti-VEGF response: rapid responders (n = 11), slow responders (n = 11), and non-responders (n = 9). In addition, patients (n = 7) who showed good response to corticosteroids but a delayed or no response to anti-VEGF therapy were analyzed. Levels of 17 different cytokines, chemokines, and growth factors in AH were measured using a multiplex immunoassay. We found higher concentrations of VEGF in rapid responders to anti-VEGF therapy compared to non-responders. In addition, slow responders to anti-VEGF treatment showed higher levels of inflammatory markers than rapid responders, but did not reach statistical significance. Finally, those patients who responded to corticosteroids but not to anti-VEGF therapy showed significantly lower levels of VEGF than patients with rapid response (p = 0.01). In conclusion, &ldquo, of AH could be useful to determine whether the predominant pathogenic event is primarily angiogenic or inflammatory in nature. This approach would allow physicians to select a more rational and cost-effective treatment. Further studies to validate these preliminary results are warranted.

Published
2019

28. Population pharmacokinetic meta-analysis of individual data to design the first randomized efficacy trial of vancomycin in neonates and young infants

Author

Evelyne Jacqz-Aigrain, Johannes N. van den Anker, Alison H. Thomson, Stéphanie Leroux, Hidefumi Nakamura, Karel Allegaert, Remedios Marques, Edmund V. Capparelli, Irja Lutsar, Bernd Meibohm, Nicolas Simon, Jumpei Saito, Valérie Biran, Mike Sharland, José Esteban Peris, Wei Zhao, Lo Yl, Centre d'Investigation Clinique 1426 (CIC 1426), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Strathclyde [Glasgow], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University of California [San Diego] (UC San Diego), University of California, Hôpital Robert Debré, 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), University of Tenessee [USA], University of Malaya [Kuala Lumpur, Malaisie], University Hospital La Fe, Valencia, Universitat de València (UV), University of Tartu, National Center for Child Health and Development [Tokyo], Glasgow Royal Infirmary, St George's Hospital, University of California (UC), University of Malaya = Universiti Malaya [Kuala Lumpur, Malaisie] (UM), Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, HAL AMU, Administrateur, and Pediatric Surgery

Subjects
0301 basic medicine, Pediatrics, vancomycin, infusion procedures, 0302 clinical medicine, newborn, Medicine, Pharmacology (medical), Randomized Controlled Trials as Topic, education.field_of_study, Maintenance dose, Anti-Bacterial Agents, 3. Good health, Infectious Diseases, drug maintenance dose, Research Design, Area Under Curve, Data Interpretation, Statistical, creatinine tests, Vancomycin, Monte Carlo Method, medicine.drug, Microbiology (medical), medicine.medical_specialty, 030106 microbiology, Population, Gestational Age, Microbial Sensitivity Tests, Loading dose, RS, 03 medical and health sciences, Pharmacokinetics, drug loading dose, 030225 pediatrics, Humans, steady state, education, Pharmacology, Dose-Response Relationship, Drug, business.industry, Body Weight, Infant, Newborn, Postmenstrual Age, infant, NONMEM, Regimen, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, regimen, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, serum
Abstract

Objectives In the absence of consensus, the present meta-analysis was performed to determine an optimal dosing regimen of vancomycin for neonates. Methods A ‘meta-model’ with 4894 concentrations from 1631 neonates was built using NONMEM, and Monte Carlo simulations were performed to design an optimal intermittent infusion, aiming to reach a target AUC0–24 of 400 mg·h/L at steady-state in at least 80% of neonates. Results A two-compartment model best fitted the data. Current weight, postmenstrual age (PMA) and serum creatinine were the significant covariates for CL. After model validation, simulations showed that a loading dose (25 mg/kg) and a maintenance dose (15 mg/kg q12h if 89% of the treated patients. Conclusions The results of a population meta-analysis of vancomycin data have been used to develop a new dosing regimen for neonatal use and to assist in the design of the model-based, multinational European trial, NeoVanc.

Published
2019

29. SEOM clinical guideline for treatment of muscle-invasive and metastatic urothelial bladder cancer (2018)

Author

B. Pérez-Valderrama, Sergio Vázquez, José Muñoz-Langa, Nuria Lainez, A. González del Alba, G. de Velasco, Cristina Caballero, Rafael Morales-Barrera, Pablo Maroto, Laura Basterretxea, [González Del Alba A] Medical Oncology Department, Hospital Universitario Puerta de Hierro-Majadahonda, Joaquin Rodrigo 2, 28222 Majadahonda, Madrid, Spain. [De Velasco G] Medical Oncology Department, Hospital Universitario Doce de Octubre, Madrid, Spain. [Lainez N] Medical Oncology Department, Complejo Hospitalario de Navarra, Pamplona, Spain. [Maroto P] Medical Oncology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. [Morales-Barrera R] Genitourinary, CNS and Sarcoma Tumors Program, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Muñoz-Langa J] Medical Oncology Department, Hospital Universitari I Politècnic la Fe, Valencia, Spain, Vall d'Hebron Barcelona Hospital Campus, and Hospital Universitari Vall d'Hebron

Subjects
0301 basic medicine, Oncology, Cancer Research, medicine.medical_treatment, Pembrolizumab, chemistry.chemical_compound, 0302 clinical medicine, Societies, Medical, Otros calificadores::/terapia [Otros calificadores], Clinical Trials as Topic, Muscle Neoplasms, Vinflunine, Bladder cancer, Neoplasms::Neoplastic Processes::Neoplasm Metastasis [DISEASES], Disease Management, Combination chemotherapy, General Medicine, Prognosis, Combined Modality Therapy, 030220 oncology & carcinogenesis, Practice Guidelines as Topic, Bufeta - Càncer - Tractament, medicine.medical_specialty, Clinical Guides in Oncology, Cystectomy, 03 medical and health sciences, Immune checkpoint inhibitors, Metàstasi, Atezolizumab, Internal medicine, medicine, Humans, Chemotherapy, Neoplasm Invasiveness, Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Urologic Neoplasms::Urinary Bladder Neoplasms [DISEASES], neoplasias::neoplasias por localización::neoplasias urogenitales::neoplasias urológicas::neoplasias de la vejiga [ENFERMEDADES], business.industry, Other subheadings::/therapy [Other subheadings], medicine.disease, Regimen, 030104 developmental biology, chemistry, Urinary Bladder Neoplasms, neoplasias::procesos neoplásicos::metástasis neoplásica [ENFERMEDADES], business
Abstract

Càncer de bufeta; Cistectomia; Quimioteràpia Cáncer de vejiga; Cistectomía; Quimioterapia Bladder cancer; Cystectomy; Chemotherapy The goal of this article is to provide recommendations about the management of muscle-invasive (MIBC) and metastatic bladder cancer. New molecular subtypes of MIBC are associated with specific clinical–pathological characteristics. Radical cystectomy and lymph node dissection are the gold standard for treatment and neoadjuvant chemotherapy with a cisplatin-based combination should be recommended in fit patients. The role of adjuvant chemotherapy in MIBC remains controversial; its use must be considered in patients with high-risk who are able to tolerate a cisplatin-based regimen, and have not received neoadjuvant chemotherapy. Bladder-preserving approaches are reasonable alternatives to cystectomy in selected patients for whom cystectomy is not contemplated either for clinical or personal reasons. Cisplatin-based combination chemotherapy is the standard first-line protocol for metastatic disease. In the case of unfit patients, carboplatin–gemcitabine should be considered the preferred first-line chemotherapy treatment option, while pembrolizumab and atezolizumab can be contemplated for individuals with high PD-L1 expression. In cases of progression after platinum-based therapy, PD-1/PD-L1 inhibitors are standard alternatives. Vinflunine is another option when anti-PD-1/PD-L1 therapy is not possible. There are no data from randomized clinical trials regarding moving on to immuno-oncology agents.

Published
2019

30. Testing for minimal residual disease in adults with acute lymphoblastic leukemia in Europe: a clinician survey

Author

Pau Montesinos, J McKendrick, Arnaud Pigneux, Heather Wieffer, Monika Brüggemann, Anja K. Pownell, Ze Cong, Xinke Zhang, Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie Clinique et Thérapie Cellulaire [CHU Bordeaux], Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux], Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, Instituto de Salud Carlos III [Madrid] (ISC), Amgen Inc, PRMA Consulting [Hampshire, UK] (Linea House), University of Technology Sydney (UTS), Universitätsklinikum Schleswig-Holstein, Amgen Inc., Bodescot, Myriam, and Hospital Universitario La Fe, Valencia

Subjects
Adult, Male, Cancer Research, Pediatrics, medicine.medical_specialty, Neoplasm, Residual, Subsequent Relapse, Cross-sectional study, Lymphoblastic Leukemia, Clinical Decision-Making, [SDV.CAN]Life Sciences [q-bio]/Cancer, lcsh:RC254-282, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Induction therapy, hemic and lymphatic diseases, MRD testing, Genetics, Medicine, Humans, In patient, Oncology & Carcinogenesis, Internet, business.industry, Minimal residual disease, Consolidation Chemotherapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Prognosis, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, Test (assessment), Europe, body regions, Cross-Sectional Studies, Oncology, 030220 oncology & carcinogenesis, Health Care Surveys, Cross-sectional survey, Female, business, ALL, 030215 immunology, Research Article
Abstract

Background In acute lymphoblastic leukemia (ALL), the presence of minimal residual disease (MRD) after induction/consolidation chemotherapy is a strong prognostic factor for subsequent relapse and mortality. Accordingly, European clinical guidelines and protocols recommend testing patients who achieve a complete hematological remission (CR) for MRD for the purpose of risk stratification. The aim of this study was to provide quantitative information regarding real-world clinical practice for MRD testing in five European countries. Methods A web-based survey was conducted in March/April 2017 in France, Germany, Italy, Spain, and the UK. The survey was developed after consultation with specialist clinicians and a review of published literature. Eligible clinicians (20 per country; 23 in Spain) were board-certified in hemato-oncology or hematology, had at least five years’ experience in their current role after training, had treated at least two patients with B-cell precursor ALL in the 12 months before the survey or at least five patients in the last five years, and had experience of testing for MRD in clinical practice. Results MRD testing is now standard practice in the treatment of adult ALL across the five European countries, with common use of recent treatment protocols which specify testing. Respondents estimated that, among clinicians in their country who conduct MRD testing, 73% of patients in first CR (CR1) and 63% of patients in second or later CR (CR2+) are tested for MRD. The median time point reported as most commonly used for the first MRD test, to establish risk status and to determine a treatment plan was four weeks after the start of induction therapy. The timing and frequency of tests is similar across countries. An average of four or five post-CR1 tests per patient in the 12 months after the first MRD test were reported across countries. Conclusions This comprehensive study of MRD testing patterns shows consistent practice across France, Germany, Italy, Spain, and the UK with respect to the timing and frequency of MRD testing, aligning with use of national protocols. MRD testing is used in clinical practice also in patients who reach CR2 + . Electronic supplementary material The online version of this article (10.1186/s12885-018-5002-5) contains supplementary material, which is available to authorized users.

Published
2018

31. Mycobacterium tuberculosis lineage 4 comprises globally distributed and geographically restricted sublineages

Author

Robert J. Wilkinson, James E. Bower, Liliana K. Rutaihwa, W. Henry Boom, Matthias Egger, Philip Noel Suffys, Elisabeth Sanchez-Padilla, Linda Gail-Bekker, Sebastien Gagneux, Issam Alani, Marie Ballif, Kathleen D. Eisenach, Jennifer L. Guthrie, Ana Gil-Brusola, Eddie M. Wampande, Willy Ssengooba, Nyanda E. Ntinginya, Rita Macedo, Petras Stakenas, Bijaya Malla, Adwoa Asante-Poku, Stefan Niemann, Lynsey Stewart-Isherwood, Mireia Coscolla, Perpetual Wangui Ndung'u, Florian Gehre, Daniela Maria Cirillo, E. Jane Carter, Sidra Ezidio Gonçalves Vasconcellos, Moses Joloba, Midori Kato-Maeda, Indira Basu, Andrea Rachow, Bouke C. de Jong, Serej D. Ley, Andrej Trauner, Hans-Peter Beck, Jackson Thomas, Dorothy Yeboah-Manu, Qingyun Liu, Tao Luo, Francesca Barletta, Véronique Penlap Beng, Janet A. M. Fyfe, Anastasia Koch, Margarida Saraiva, Sven Hoffner, Daniela Brites, Sahal Al-Hajoj, Griselda Tudo Vilanova, Maria Globan, Qian Gao, Helmi Mardassi, Maryline Bonnet, Philip Supply, Iñaki Comas, Valeriu Crudu, Girts Skenders, Francine Ntoumi, Frances B. Jamieson, Olga Domnica Moldovan, Leïla Jeljeli, Gunturu Revathi, Milagros Moreno, Suriya Akter, Sonia Borrell, Kadri Toit, Matthias Frank, Michael Hoelscher, Lameck Diero, Daiva Bakonyte, David Stucki, Lukas Fenner, Larissa Otero, Roland Diel, University of Basel (Unibas), Swiss Tropical Institute, Swiss Tropical and Public Health Institute [Basel], Forschungszentrum Borstel - Research Center Borstel, German Center for Infection Research, Borstel Site, Institute of Social and Preventive Medicine [Bern] (ISPM), Universität Bern [Bern], Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP), Key Laboratory of Medical Molecular Virology of the Ministries of Education and Health, Institutes of Biomedical Sciences and Institute of Medical Microbiology, Fudan University, Laboratory of Infection and Immunity, School of Basic Medical Science, West China Center of Medical Sciences, Sichuan University [Chengdu] (SCU), University of California at San Francisco, University of California [San Francisco] (UCSF), University of California-University of California, School of Medicine, Laboratorio Nacional de Saude Publica, Hospital Nossa Senhora da Paz, Servei de Microbiologia, Hospital Clínic–ISGlobal, Barcelona, Victorian Infectious Diseases Reference Laboratory, Public Health Ontario - Santé publique Ontario, Noguchi Memorial Institute for Medical Research [Accra, Ghana] (NMIMR), University of Ghana, Makerere University College of Health Sciences, Department of Global Health, University of Amsterdam [Amsterdam] (UvA), Department of Molecular Biology and Microbiology, Case Western Reserve University [Cleveland], Lab Plus, Auckland City Hospital, ICVS/3B's—PT Government Associate Laboratory, Braga, Molecular Biology Applied to Mycobacteria / Biologia Molecular Aplicada a Micobactérias [Rio de Janeiro], Instituto Oswaldo Cruz / Oswaldo Cruz Institute [Rio de Janeiro] (IOC), Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institute of Infectious Disease and Molecular Medicine, and Department of Clinical Laboratory Sciences, University of Cape Town, Department of Medicine, Imperial College London, Francis Crick Institute Mill Hill Laboratory, London, Papua New Guinea Institute of Medical Research (PNG-IMR), Institute of Tropical Medicine [Antwerp] (ITM), Tartu University Hospital United Laboratories, Mycobacteriology, Epicentre [Paris] [Médecins Sans Frontières], Institute of Tropical Medicine and Infectious Diseases (ITROMID), Jomo Kenyatta University of Agriculture and Technology (JKUAT), Nairobi, Department of Microbiology, University Hospital La Fe, Valencia, University of Tübingen [Germany], Fondation Congolaise pour la Recherche Médicale, Université Marien Gouabi, Brazzaville, University of Yaoundé [Cameroun], University of Arkansas for Medical Sciences (UAMS), Department of Medical Laboratory Technology, Faculty of Medical Technology, Baghdad, Department of Pathology, Aga Khan University Hospital (AKUH), Nairobi, Medical Research Council, Fajara, Right to Care and the Clinical HIV Research Unit, University of the Witwatersrand [Johannesburg] (WITS), Division of Infectious Diseases and Tropical Medicine = Abteilung für infektions und tropenmedizin [Munich, Germany], Klinikum der Universität [München]-Ludwig-Maximilians-Universität München (LMU), National Institute of Medical Research, Mbeya Medical Research Centre (NIMR-MMRC), Mbeya, Emerging Bacterial Pathogen Unit, San Raffaele Scientific Institute, WHO Supranational TB Reference Laboratory, Department of Microbiology, Public Health Agency of Sweden, Department of Immunology and Cell Biology, Institute of Biotechnology, Vilnius University [Vilnius], Institute for Epidemiology, Schleswig-Holstein University Hospital, Kiel, Marius Nasta Institute of Pneumology, Department of Infection and Immunity, King Faisal Specialist Hospital and Research Centre, Riyadh, Instituto de Medicina Tropical Alexander von Humboldt, Molecular Epidemiology Unit–Tuberculosis, Instituto de Medicina Tropical 'Alexander von Humboldt' (IMT AvH), Universidad Peruana Cayetano Heredia (UPCH)-Universidad Peruana Cayetano Heredia (UPCH), Warren Alpert Medical School of Brown University, Moi University School of Medicine, Eldoret, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), CIBER Epidemiology and Public Health, Madrid, [et. al.], Universidade do Minho, Wellcome Trust, Universität Bern [Bern] (UNIBE), University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), Victorian Infectious Diseases Reference Laboratory [Melbourne, Australia] (VIDRL), Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Ludwig-Maximilians-Universität München (LMU)-Klinikum der Universität [München], King Faisal Specialist Hospital and Research Centre (KFSH & RC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (1965 - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)

Subjects
0301 basic medicine, Infecções Respiratórias, [SDV]Life Sciences [q-bio], Generalist and specialist species, Global Health, ANTIGENIC VARIATION, Polymorphism, Genetic/genetics, POPULATION, ComputingMilieux_MISCELLANEOUS, Genetics & Heredity, education.field_of_study, RESISTANT TUBERCULOSIS, Human migration, Ecology, 11 Medical And Health Sciences, Genomics, SOUTH-AFRICA, 3. Good health, Mycobacterium tuberculosis/classification/genetics/isolation & purification, Phylogeography, GENETIC DIVERSITY, Life Sciences & Biomedicine, DNA, Bacterial, Lineage (genetic), Genotype, Niche, Population, Tuberculosis/genetics/microbiology, Biology, Article, Host Specificity, 03 medical and health sciences, HIV-INFECTION, Genetics, Humans, Tuberculosis, DNA, Bacterial/analysis, education, Ecological niche, PATHOGENS, Science & Technology, Polymorphism, Genetic, Obligate, business.industry, Mycobacterium tuberculosis, 06 Biological Sciences, biology.organism_classification, PAPUA-NEW-GUINEA, EVOLUTION, Genomics/methods, 030104 developmental biology, Evolutionary biology, business, GENOMIC DIVERSITY, purl.org/pe-repo/ocde/ford#1.06.07 [https], Developmental Biology, Mycobacterium
Abstract

Generalist and specialist species differ in the breadth of their ecological niches. Little is known about the niche width of obligate human pathogens. Here we analyzed a global collection of Mycobacterium tuberculosis lineage 4 clinical isolates, the most geographically widespread cause of human tuberculosis. We show that lineage 4 comprises globally distributed and geographically restricted sublineages, suggesting a distinction between generalists and specialists. Population genomic analyses showed that, whereas the majority of human T cell epitopes were conserved in all sublineages, the proportion of variable epitopes was higher in generalists. Our data further support a European origin for the most common generalist sublineage. Hence, the global success of lineage 4 reflects distinct strategies adopted by different sublineages and the influence of human migration., We thank S. Lecher, S. Li and J. Zallet for technical support. Calculations were performed at the sciCORE scientific computing core facility at the University of Basel. This work was supported by the Swiss National Science Foundation (grants 310030_166687 (S.G.) and 320030_153442 (M.E.) and Swiss HIV Cohort Study grant 740 to L.F.), the European Research Council (309540-EVODRTB to S.G.), TB-PAN-NET (FP7-223681 to S.N.), PathoNgenTrace projects (FP7-278864-2 to S.N.), SystemsX.ch (S.G.), the German Center for Infection Research (DZIF; S.N.), the Novartis Foundation (S.G.), the Natural Science Foundation of China (91631301 to Q.G.), and the National Institute of Allergy and Infectious Diseases (5U01-AI069924-05) of the US National Institutes of Health (M.E.).

Published
2016

32. Primary Breast Lymphoma: Analysis of 55 Cases of the Spanish Lymphoma Oncology Group

Author

Jesús Alfaro, José Miramón, José Gómez-Codina, Rut Álvarez, Javier Lavernia, Esteban Nogales, Mariano Provencio, Francisco Ramon Garcia Arroyo, David Aguiar-Bujanda, Natividad Martínez, Fernando Fabio Franco Pérez, Francisco Menarguez, Mayte Delgado, Maria Torrente, Miguel Ángel Marín, Ana Royuela, Delvys Rodriguez Abreu, Cristina Quero, Josep Gumá, Marta Llanos, [Franco Perez, Fernando] Hosp Univ Puerta Hierro, Dept Med Oncol, Majadahonda, Spain, [Torrente, Maria] Hosp Univ Puerta Hierro, Dept Med Oncol, Majadahonda, Spain, [Provencio, Mariano] Hosp Univ Puerta Hierro, Dept Med Oncol, Majadahonda, Spain, [Lavernia, Javier] Inst Valenciano Oncolog, Dept Med Oncol, Valencia, Spain, [Aguiar-Bujanda, David] Hosp Univ Gran Canaria Doctor Negr, Dept Med Oncol, Las Palmas Gran Canaria, Spain, [Miramon, Jose] Hosp Serrania Ronda, Dept Med Oncol, Malaga, Spain, [Guma, Josep] Hosp Univ Sant Joan Reus, Dept Med Oncol, Reus, Spain, [Alvarez, Rut] Hosp Univ Virgen Salud, Dept Med Oncol, Toledo, Spain, [Gomez-Codina, Jose] Hosp Univ Politecn Le Fe, Dept Med Oncol, Valencia, Spain, [Garcia Arroyo, Francisco] Complejo Hospitalario Pontevedra, Dept Med Oncol, Pontevedra, Spain, [Llanos, Marta] Hosp Univ Canarias, Dept Med Oncol, San Cristobal la Laguna, Spain, [Marin, Miguel] Hosp Clinico Univ Virgen La Arrixaca, Dept Med Oncol, Murcia, Spain, [Alfaro, Jesus] Inst Oncol Kurxa, Dept Med Oncol, Donistia, Spain, [Quero, Cristina] Hosp Univ Virgen La Victoria, Dept Med Oncol, Malaga, Spain, [Delgado, Mayte] Hosp Univ San Cecilio, Dept Med Oncol, Granada, Spain, [Nogales, Esteban] Hosp Univ Virgen La Macarena, Dept Med Oncol, Seville, Spain, [Menarguez, Francisco] Hosp Gen Univ Elche, Dept Med Oncol, Alicante, Spain, [Martinez, Natividad] Hosp Gen Univ Elche, Dept Med Oncol, Alicante, Spain, [Royuela, Ana] Hosp Univ Puerta Hierro, Dept Biostat, Majadahonda, Spain, [Abreu, Delvys] Hosp Univ Insular Gran Canaria, Dept Med Oncol, Las Palmas Gran Canaria, Spain, [Franco Pérez,F, Torrente,M, Provencio,M] Department of Medical Oncology, Hospital Universitario Puerta de Hierro, Majadahonda, Spain. [Lavernia,J] Department of Medical Oncology, Instituto Valenciano de Oncología, Valencia, Spain. [Aguiar-Bujanda,D] Department of Medical Oncology, Hospital Universitario de Gran Canaria Doctor Negrín, Las Palmas de Gran Canarias, Spain. [Miramón,J] Department of Medical Oncology, Hospital Serranía de Ronda, Málaga, Spain. [Gumá,J] Department of Medical Oncology, Hospital Universitari Sant Joan de Reus, Reus, Spain. [Álvarez,R] Department of Medical Oncology, Hospital Universitario Virgen de la Salud, Toledo, Spain. [Gómez-Codina,J] Department of Medical Oncology, Hospital Universitari i Politècnic La Fe, Valencia, Spain. [García Arroyo,F] Department of Medical Oncology, Complejo Hospitalario de Pontevedra, Pontevedra, Spain. [Llanos,M] Department of Medical Oncology, Hospital Universitario de Canarias, San Cristóbal de La Laguna, Spain. [Marin,M] Department of Medical Oncology, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain. [Alfaro,J] Department of Medical Oncology, Instituto Oncológico de Kutxa, Donostia, Spain. [Quero,C] Department of Medical Oncology, Hospital Universitario Virgen de la Victoria, Málaga, Spain. [Delgado,M] Department of Medical Oncology, Hospital Universitario San Cecilio, Granada, Spain. [Nogales,E] Department of Medical Oncology, Hospital Universitario Virgen de la Macarena, Sevilla, Spain. [Menarguez,F, and Martinez,N] Department of Medical Oncology, Hospital General Universitario de Elche, Alicante, Spain. [Royuela,A] Department of Biostatistics, Hospital Universitario Puerta de Hierro, Majadahonda, Spain. [Abreu,D] Department of Medical Oncology, Hospital Universitario Insular de Gran Canaria, Las Palmas de Gran Canarias, Spain.

Subjects
0301 basic medicine, Oncology, Male, Cancer Research, Survival, Lymphoma, medicine.medical_treatment, Anatomy::Body Regions::Breast::Mammary Glands, Human [Medical Subject Headings], neoplasias de la mama, cancer de mama, oncología médica, Medical Oncology, radioterapia, Supervivencia sin rnfermedad, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Diseases::Hemic and Lymphatic Diseases::Lymphatic Diseases::Lymphoproliferative Disorders::Lymphoma::Lymphoma, Non-Hodgkin [Medical Subject Headings], immune system diseases, hemic and lymphatic diseases, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy [Medical Subject Headings], Breast, Neoplasms of the breast, Stage (cooking), Multicenter, Lymph node, inmunoterapia, Aged, 80 and over, Patient, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Remission Induction [Medical Subject Headings], B-cell lymphoma, Incidence (epidemiology), Follow-up, Lymphoma, Non-Hodgkin, Lumpectomy, Ganglios linfáticos, Diseases::Hemic and Lymphatic Diseases::Lymphatic Diseases::Lymphoproliferative Disorders::Lymphoma [Medical Subject Headings], Hematology, Middle Aged, Prognosis, medicine.anatomical_structure, Treatment Outcome, Consenso, Non-hodgkins-lymphoma, mama, 030220 oncology & carcinogenesis, Rituximab, Female, Immunotherapy, Incidencia, medicine.drug, Adult, medicine.medical_specialty, tumores de mama, Antineoplastic Agents, Breast Neoplasms, Outcomes, Disease-Free Survival, Breast Neoplasms, Male, 03 medical and health sciences, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Morbidity::Incidence [Medical Subject Headings], Internal medicine, medicine, Chemotherapy, Humans, Extranodal lymphoma, linfoma, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Disease-Free Survival [Medical Subject Headings], Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Aged, linfoma no Hodgkin, Radiotherapy, business.industry, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Psychology, Social::Group Processes::Consensus [Medical Subject Headings], Prognostic-factors, medicine.disease, Radiation therapy, 030104 developmental biology, Check Tags::Female [Medical Subject Headings], Glándulas mamarias humanas, Quimioterapia, Lymph Nodes, business, Anatomy::Tissues::Lymphoid Tissue::Lymph Nodes [Medical Subject Headings], Clinicopathological features
Abstract

We reviewed 55 patients diagnosed with primary breast lymphoma, stages IE and IIE, in 16 Spanish institutions. Of the 55 cases, 96.4% corresponded to non-Hodgkin lymphoma. Results of 5-year progression-free and overall survival were 73% and 76%, respectively. Current treatments achieve good control of the disease, with an overall survival of 5 years in 80% of the patients.Introduction: Primary breast lymphoma is a rare form of localized extranodal lymphoma, which affects the mammary glands unilaterally or bilaterally, and can also affect the regional lymph nodes. Materials and Methods: We reviewed 55 patients, with disease stages IE and IIE, diagnosed in 16 Spanish institutions between 1989 and 2016. A serial of clinical variables and treatment were collected, and overall survival (OS) and progression-free survival (PFS) were calculated. Results: Of the 55 patients, 96.4% were women with an average age of 69 years. A total of 53 patients corresponded to non-Hodgkin lymphoma (NHL), of whom 36.3% had lymph node involvement upon diagnosis. Of the patients, 58.2% were stage IE, and 41.8% were stage IIE. Treatments received included radiotherapy (36.3%), chemotherapy (85.5%), and rituximab (in 38 of the 45 patients with NHL treated with chemotherapy). In all, 82.2% of complete responses were achieved. OS and progression-free survival at 5 years in NHL patients was 76% and 73%, respectively. Conclusion: Current treatments (chemotherapy, immunotherapy, and radiotherapy) achieve good control of the disease, with an OS of 5 years in 80% of the patients, although there is no consensus in treatment, given the scarce incidence of these lymphomas. (C) 2016 The Authors. Published by Elsevier Inc.

Published
2016

33. Daptomycin plus fosfomycin versus daptomycin monotherapy in treating MRSA: protocol of a multicentre, randomised, phase III trial

Author

Shaw Perujo, Evelyn, Miró Meda, José M., Puig-Asensio, M., Pigrau, C., Barcenilla, F., Murillas Angoiti, Javier, Garcia-Pardo, G., Espejo, Elena, Padilla, Belén, Garcia-Reyne, A., Pasquau, Juan, Rodríguez Baño, Jesús, López-Contreras, J., Montero, Miguel, Calle, Cristina de la, Pintado, Vicente, Calbo, E., Gasch, Oriol, Montejo, Miguel, Salavert, Miguel, Garcia-Pais, M.J., Carratalà, Jordi, Pujol Rojo, Miquel, Spanish Network for Research in Infectious Diseases (REIPI), Instituto de Salud Carlos III, Madrid, Spain, GEIH (Hospital Infection Study Group), Spanish Network for Research in Infectious Diseases (REIPI RD12/0015), Instituto de Salud Carlos III, Madrid, Spain, GEIH (Hospital Infection Study Group), [Shaw ,E, Carratalà,J, Pujol,M] Hospital Universitari de Bellvitge-IDIBELL, Hospitalet de Llobregat, Barcelona, Spain. [Miró,JM, de la Calle C] Hospital Universitari Clínic-IDIBAPS, Barcelona, Spain. [Puig-Asensio,M, Pigrau,C] Hospital Universitari Vall d'Hebron, Barcelona, Spain. [Barcenilla,F] Hospital Universitari Arnau de Vilanova, Lleida, Spain. [Murillas J] Hospital Universitari Son Espases, Mallorca, Spain. [Garcia-Pardo,G] Hospital Universitari Joan XXIII, Tarragona, Spain. [Espejo,E] Hospital Universitari de Terrassa, Terrassa, Barcelona, Spain. [Padilla,B] Hospital Universitario Gregorio Marañon, Madrid, Spain. [Garcia-Reyne,A] Hospital Universitario 12 de Octubre, Madrid, Spain. [Pasquau,J] Hospital Universitario Virgen de las Nieves, Granada, Spain. [Rodriguez-Baño,J] Hospital Universitario Virgen Macarena, Sevilla, Spain. [López-Contreras,J] Hospital Universitari Santa Creu i Sant Pau, Barcelona, Spain. [Montero,M] Hospital Universitari Parc de Salut Mar, Barcelona, Spain. [Pintado,V] Hospital Universitario Ramón y Cajal, Madrid, Spain. [Calbo,E] Hospital Universitari Mutúa de Terrassa, Barcelona, Spain. [Gasch,O] Corporació Sanitaria Parc Taulí, Sabadell, Barcelona, Spain. [Montejo,M] Hospital Universitario de Cruces, Barakaldo, Spain. [Salavert,M] Hospital Universitari i Politècnic la Fe, Valencia, Spain. [Garcia-Pais,MJ] Hospital Universitario Lucus Augusti, Lugo, Spain., This work is supported by grant funding from the National Institute of Health Research, Instituto de Salud Carlos III (ISCIII), Ministerio de Economía y Competitividad. Gobierno de España (Expediente PI12/01907)., and Universitat de Barcelona

Subjects
Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Recurrence [Medical Subject Headings], Pediatrics, bacteraemia, Insuficiencia del Tratamiento, daptomycin, humanos, España, adolescente, Bacteremia, Antibióticos Antituberculosos, medicine.disease_cause, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Treatment Outcome::Treatment Failure [Medical Subject Headings], combination therapy, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Bacterièmia, Clinical trials, infecciones estafilocócicas, Protocol, polycyclic compounds, Organisms::Bacteria::Endospore-Forming Bacteria::Gram-Positive Endospore-Forming Bacteria::Gram-Positive Endospore-Forming Rods::Staphylococcaceae::Staphylococcus::Staphylococcus aureus::Methicillin-Resistant Staphylococcus aureus [Medical Subject Headings], Geographicals::Geographic Locations::Europe::Spain [Medical Subject Headings], Adulto, resultado del tratamiento, Diseases::Bacterial Infections and Mycoses::Bacterial Infections::Bacteremia [Medical Subject Headings], Staphylococcus aureus Resistente a Meticilina, bacteriemia, General Medicine, adulto, Staphylococcal Infections, Anti-Bacterial Agents, Humanos, Estafilococs daurats, Drug Combinations, Análisis de Intención de Tratar, Infectious Diseases, Treatment Outcome, Antibacterianos, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Epidemiologic Study Characteristics as Topic::Clinical Trials as Topic::Controlled Clinical Trials as Topic::Randomized Controlled Trials as Topic::Intention to Treat Analysis [Medical Subject Headings], Research Design, Chemicals and Drugs::Organic Chemicals::Amides::Lactams::beta-Lactams::Penicillins::Methicillin [Medical Subject Headings], pruebas de sensibilidad microbiana, daptomicina, lipids (amino acids, peptides, and proteins), antibacterianos, medicine.drug, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Anti-Bacterial Agents [Medical Subject Headings], Adult, Methicillin-Resistant Staphylococcus aureus, medicine.medical_specialty, Staphylococcus aureus, Combination therapy, Adolescent, Resultado del Tratamiento, Chemicals and Drugs::Polycyclic Compounds::Macrocyclic Compounds::Peptides, Cyclic::Daptomycin [Medical Subject Headings], Staphylococcus aureus resistente a meticilina, Recurrencia, Microbial Sensitivity Tests, Fosfomycin, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Anti-Bacterial Agents::Antibiotics, Antitubercular [Medical Subject Headings], medicine, Named Groups::Persons::Age Groups::Adult [Medical Subject Headings], Humans, Septicèmia, Adverse effect, Resistència als medicaments, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Treatment Outcome [Medical Subject Headings], Intention-to-treat analysis, methicillin-resistant Staphylococcus aureus (MRSA), business.industry, Septicemia, biochemical phenomena, metabolism, and nutrition, medicine.disease, bacterial infections and mycoses, Methicillin-resistant Staphylococcus aureus, Clinical trial, fosfomicina, Drug resistance, combinaciones de fármacos, Daptomicina, Bacteriemia, Daptomycin, business, diseño de la investigación, Assaigs clínics, Meticilina
Abstract

Introduction: Despite the availability of new antibiotics such as daptomycin, methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia continues to be associated with high clinical failure rates. Combination therapy has been proposed as an alternative to improve outcomes but there is a lack of clinical studies. The study aims to demonstrate that combination of daptomycin plus fosfomycin achieves higher clinical success rates in the treatment of MRSA bacteraemia than daptomycin alone. Methods and analysis: A multicentre open-label, randomised phase III study. Adult patients hospitalised with MRSA bacteraemia will be randomly assigned (1:1) to group 1: daptomycin 10 mg/kg/24 h intravenous; or group 2: daptomycin 10 mg/kg/24 h intravenous plus fosfomycin 2 gr/6 g intravenous. The main outcome will be treatment response at week 6 after stopping therapy (test-of-cure (TOC) visit). This is a composite variable with two values: Treatment success: resolution of clinical signs and symptoms (clinical success) and negative blood cultures (microbiological success) at the TOC visit. Treatment failure: if any of the following conditions apply: (1) lack of clinical improvement at 72 h or more after starting therapy; (2) persistent bacteraemia (positive blood cultures on day 7); (3) therapy is discontinued early due to adverse effects or for some other reason based on clinical judgement; (4) relapse of MRSA bacteraemia before the TOC visit; (5) death for any reason before the TOC visit. Assuming a 60% cure rate with daptomycin and a 20% difference in cure rates between the two groups, 103 patients will be needed for each group (alpha:0.05, beta: 0.2). Statistical analysis will be based on intention to treat, as well as per protocol and safety analysis. Ethics and dissemination: The protocol was approved by the Spanish Medicines and Healthcare Products Regulatory Agency (AEMPS). The sponsor commits itself to publishing the data in first quartile peer-review journals within 12 months of the completion of the study., This work is supported by grant funding from the National Institute of Health Research, Instituto de Salud Carlos III (ISCIII), Ministerio de Economia y Competitividad. Gobierno de Espana (Expediente PI12/01907).

Published
2015

34. Human neonatal hepatocyte transplantation induces long-term rescue of unconjugated hyperbilirubinemia in the Gunn rat

Author

Anne Myara, Eugenia Pareja, Laia Tolosa, José V. Castell, María José Gómez-Lechón, Silvia López, María Teresa Donato, Tuan Huy Nguyen, Unidad de Hepatología Experimental [Valencia, Spain], Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, Unidad de Cirugia Hepatobiliopancreatica y Transplante Hepatico [Valencia, Spain], Hospital La Fe [Valencia, Spain], Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Liver Unit, Clínica Universitaria, CIBER-EHD, Departamento de Bioquımica y Biologıa Molecular [Valencia, Spain] (Facultad de Medicina), Universidad de Valencia, Service de Biologie [GH Saint-Joseph - APHP], Centre hospitalier Saint-Joseph [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Funding was provided by the European Union (INNOVALIV, FP7-HEALTH-2011 number 278152) and Generalitat Valenciana(Conselleria de Educacion GV2014/116). Laia Tolosa was a recipient of a Sara Borrell contract from the Instituto de Salud Carlos III of the Spanish Ministry of Economy and Competitiveness., European Project: 278152,HEALTH,FP7-HEALTH-2011-two-stage,INNOVALIV(2011), Hospital Universitari La Fe, Le Bihan, Sylvie, and Innovative strategies to generate human hepatocytes for treatment of metabolic Liver diseases: Tools for personalized cell therapy - INNOVALIV - - HEALTH2011-12-01 - 2014-11-30 - 278152 - VALID

Subjects
Male, medicine.medical_specialty, Glucuronosyltransferase, Bilirubin, medicine.medical_treatment, Rats, Gunn, Liver transplantation, chemistry.chemical_compound, Internal medicine, medicine, Animals, Humans, Progenitor cell, Unconjugated hyperbilirubinemia, Aged, Cell Proliferation, Crigler-Najjar Syndrome, Aged, 80 and over, Transplantation, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Hepatology, biology, business.industry, Infant, Newborn, Middle Aged, Gunn rat, Propranolol, Liver regeneration, 3. Good health, Liver Regeneration, Endocrinology, chemistry, Liver, Immunology, biology.protein, Hepatocytes, Surgery, Female, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Crigler-Najjar type 1 disease is a rare inherited metabolic disease characterized by high levels of unconjugated bilirubin due to the complete absence of hepatic uridine diphosphoglucuronate-glucuronosyltransferase activity. Hepatocyte transplantation (HT) has been proposed as an alternative treatment for Crigler-Najjar syndrome, but it is still limited by the quality and the low engraftment and repopulation ability of the cells used. Because of their attachment capability and expression of adhesion molecules as well as the higher proportion of hepatic progenitor cells, neonatal hepatocytes may have an advantage over adult cells. Adult or neonatal hepatocytes were transplanted into Gunn rats, a model for Crigler-Najjar disease. Engraftment and repopulation were studied and compared by immunofluorescence (IF). Additionally, the serum bilirubin levels, the presence of bilirubin conjugates in rat serum, and the expression of uridine diphosphate glucuronosyltransferase 1 family polypeptide A1 (UGT1A1) in rat liver samples were also analyzed. Here we show that neonatal HT results in long-term correction in Gunn rats. In comparison with adult cells, neonatal cells showed better engraftment and repopulation capability 3 days and 6 months after transplantation, respectively. Bilirubinemia decreased in the transplanted animals during the whole experimental follow-up (6 months). Bilirubin conjugates were also present in the serum of the transplanted animals. Western blots and IF confirmed the presence and expression of UGT1A1 in the liver. This work is the first to demonstrate the advantage of using neonatal hepatocytes for the treatment of Crigler-Najjar in vivo.

Published
2014

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