34 results on '"Miriam Cebey-López"'
Search Results
2. Relationship between molecular pathogen detection and clinical disease in febrile children across Europe: a multicentre, prospective observational studyResearch in context
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Priyen Shah, Marie Voice, Leonides Calvo-Bado, Irene Rivero-Calle, Sophie Morris, Ruud Nijman, Claire Broderick, Tisham De, Irini Eleftheriou, Rachel Galassini, Aakash Khanijau, Laura Kolberg, Mojca Kolnik, Aleksandra Rudzate, Manfred G. Sagmeister, Nina A. Schweintzger, Fatou Secka, Clare Thakker, Fabian van der Velden, Clementien Vermont, Katarina Vincek, Philipp K.A. Agyeman, Aubrey J. Cunnington, Ronald De Groot, Marieke Emonts, Katy Fidler, Taco W. Kuijpers, Marine Mommert-Tripon, Karen Brengel-Pesce, Francois Mallet, Henriette Moll, Stéphane Paulus, Marko Pokorn, Andrew Pollard, Luregn J. Schlapbach, Ching-Fen Shen, Maria Tsolia, Effua Usuf, Michiel van der Flier, Ulrich von Both, Shunmay Yeung, Dace Zavadska, Werner Zenz, Victoria Wright, Enitan D. Carrol, Myrsini Kaforou, Federico Martinon-Torres, Colin Fink, Michael Levin, Jethro Herberg, Irene Rivero Calle, Manfred Sagmeister, Nina Schweintzger, Fabian Van der Velden, Taco Kuijpers, Michiel Van der Flier, Ulrich Von Both, Lucas Baumard, Evangelos Bellos, Lachlan Coin, Giselle D'Souza, Dominic Habgood-Coote, Shea Hamilton, Cllive Hoggart, Sara Hourmat, Heather Jackson, Naomi Lin, Stephanie Menikou, Samuel Nichols, Ivonne Pena Paz, Oliver Powell, Ortensia Vito, Clare Wilson, Amina Abdulla, Ladan Ali, Sarah Darnell, Rikke Jorgensen, Ian Maconochie, Sobia Mustafa, Salina Persand, Ben Walsh, Molly Stevens, Nayoung Kim, Eunjung Kim, Benjamin Pierce, Julia Dudley, Vivien Richmond, Emma Tavliavini, Ching-Chuan Liu, Shih-Min Wang, Fernando Álves González, Cristina Balo Farto, Ruth Barral-Arca, María Barreiro Castro, Xabier Bello, Mirian Ben García, Sandra Carnota, Miriam Cebey-López, María José Curras-Tuala, Carlos Durán Suárez, Luisa García Vicente, Alberto Gómez-Carballa, Jose Gómez Rial, Pilar Leboráns Iglesias, Nazareth Martinón-Torres, José María Martinón Sánchez, Belén Mosquera Pérez, Jacobo Pardo-Seco, Lidia Piñeiro Rodríguez, Sara Pischedda, Sara Ray Vázquez, Carmen Rodríguez-Tenreiro, Lorenzo Redondo-Collazo, Miguel Sadiki Ora, Antonio Sallas, Sonia Serén Fernández, Cristina Serén Trasorras, Marisol Vilas Iglesias, Anda Balode, Arta Bãrdzdina, Dãrta Deksne, Dace Gardovska, Dagne Grãvele, Ilze Grope, Anija Meiere, Ieve Nokalna, Jana Pavãre, Zanda Pučuka, Katrīna Selecka, Dace Svile, Urzula Nora Urbãne, Kalifa Bojang, Syed M.A. Zaman, Suzanne Anderson, Anna Roca, Isatou Sarr, Momodou Saidykhan, Saffiatou Darboe, Samba Ceesay, Umberto D'alessandro, Dorine M. Borensztajn, Nienke N. Hagedoorn, Chantal Tal, Joany Zachariasse, W. Dik, Christoph Aebi, Christoph Berger, Verena Wyss, Mariama Usman, Eric Giannoni, Martin Stocker, Klara M. Posfay-Barbe, Ulrich Heininger, Sara Bernhard-Stirnemann, Anita Niederer-Loher, Christian Kahlert, Giancarlo Natalucci, Christa Relly, Thomas Riedel, Elizabeth Cocklin, Rebecca Jennings, Joanne Johnson, Simon Leigh, Karen Newall, Sam Romaine, Maria Tambouratzi, Antonis Marmarinos, Marietta Xagorari, Kelly Syggelou, Nikos Spyridis, Jennifer Blackmore, Rebekah Harrison, Benno Kohlmaier, Daniela S. Kohlfürst, Christoph Zurl, Alexander Binder, Susanne Hösele, Manuel Leitner, Lena Pölz, Glorija Rajic, Sebastian Bauchinger, Hinrich Baumgart, Martin Benesch, Astrid Ceolotto, Ernst Eber, Siegfried Gallisti, Gunther Gores, Harald Haidl, Almuthe Hauer, Christa Hude, Markus Keldorfer, Larissa Krenn, Heidemarie Pilch, Andreas Pfleger, Klaus Pfurtscheller, Gudrun Nordberg, Tobias Niedrist, Siegfried Rödl, Andrea Skrabl-Baumgartner, Matthias Sperl, Laura Stampfer, Volker Strenger, Holger Till, Andreas Trobisch, Sabine Löffler, Juan Emmanuel Dewez, Martin Hibberd, David Bath, Alec Miners, Elizabeth Fitchett, Catherine Wedderburn, Anne Meierford, Baptiste Leurent, Marien I. De Jonge, Koen van Aerde, Wynand Alkema, Bryan van den Broek, Jolein Gloerich, Alain J. Van Gool, Stefanie Henriet, Martijn Huijnen, Ria Philipsen, Esther Willems, G.P.J.M. Gerrits, M. Van Leur, J. Heidema, L. De Haan, C.J. Miedema, C. Neeleman, C.C. Obihara, G.A. Tramper-Stranders, Rama Kandasamy, Michael J. Carter, Daniel O'Connor, Sagida Bibi, Dominic F. Kelly, Meeru Gurung, Stephen Throson, Imran Ansari, David R. Murdoch, Shrijana Shrestha, Zoe Oliver, Emma Lim, Lucille Valentine, Karen Allen, Kathryn Bell, Adora Chan, Stephen Crulley, Kirsty Devine, Daniel Fabian, Sharon King, Paul McAlinden, Sam McDonald, Anne McDonell, Alisa Pickering, Evelyn Thomson, Amanda Wood, Diane Wallia, Phil Woodsford, Frances Baxter, Ashley Bell, Mathew Rhodes, Rachel Agbeko, Christine Mackerness, Bryan Baas, Lieke Kloosterhuis, Wilma Oosthoek, Tasnim Arif, Joshua Bennet, Kalvin Collings, Ilona Van der Giessen, Alex Martin, Aqeela Rashid, Emily Rowlands, Joshua Soon, Gabriella De Vries, Mike Martin, Ravi Mistry, Manuela Zwerenz, Judith Buschbeck, Christoph Bidlingmaier, Vera Binder, Katharina Danhauser, Nikolaus Haas, Matthias Griese, Matthias Kappler, Eberhard Lurz, Georg Muench, Karl Reiter, Carola Schoen, Alexandre Pachot, Marine Mommert, Tina Plankar Srovin, Natalija Bahovec, Petra Prunk, Veronika Osterman, Tanja Avramoska, Ilse Jongerius, J.M. van den Berg, D. Schonenberg, A.M. Barendregt, D. Pajkrt, M. van der Kuip, A.M. van Furth, Evelien Sprenkeler, Judith Zandstra, G. van Mierlo, and J. Geissler
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Molecular diagnostics ,Diagnostic ,Febrile illness ,Infectious disease ,Bacterial ,Viral ,Public aspects of medicine ,RA1-1270 - Abstract
Summary: Background: The PERFORM study aimed to understand causes of febrile childhood illness by comparing molecular pathogen detection with current clinical practice. Methods: Febrile children and controls were recruited on presentation to hospital in 9 European countries 2016–2020. Each child was assigned a standardized diagnostic category based on retrospective review of local clinical and microbiological data. Subsequently, centralised molecular tests (CMTs) for 19 respiratory and 27 blood pathogens were performed. Findings: Of 4611 febrile children, 643 (14%) were classified as definite bacterial infection (DB), 491 (11%) as definite viral infection (DV), and 3477 (75%) had uncertain aetiology. 1061 controls without infection were recruited. CMTs detected blood bacteria more frequently in DB than DV cases for N. meningitidis (OR: 3.37, 95% CI: 1.92–5.99), S. pneumoniae (OR: 3.89, 95% CI: 2.07–7.59), Group A streptococcus (OR 2.73, 95% CI 1.13–6.09) and E. coli (OR 2.7, 95% CI 1.02–6.71). Respiratory viruses were more common in febrile children than controls, but only influenza A (OR 0.24, 95% CI 0.11–0.46), influenza B (OR 0.12, 95% CI 0.02–0.37) and RSV (OR 0.16, 95% CI: 0.06–0.36) were less common in DB than DV cases. Of 16 blood viruses, enterovirus (OR 0.43, 95% CI 0.23–0.72) and EBV (OR 0.71, 95% CI 0.56–0.90) were detected less often in DB than DV cases. Combined local diagnostics and CMTs respectively detected blood viruses and respiratory viruses in 360 (56%) and 161 (25%) of DB cases, and virus detection ruled-out bacterial infection poorly, with predictive values of 0.64 and 0.68 respectively. Interpretation: Most febrile children cannot be conclusively defined as having bacterial or viral infection when molecular tests supplement conventional approaches. Viruses are detected in most patients with bacterial infections, and the clinical value of individual pathogen detection in determining treatment is low. New approaches are needed to help determine which febrile children require antibiotics. Funding: EU Horizon 2020 grant 668303.
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- 2023
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3. Impact of infection on proteome-wide glycosylation revealed by distinct signatures for bacterial and viral pathogens
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Esther Willems, Jolein Gloerich, Anouk Suppers, Michiel van der Flier, Lambert P. van den Heuvel, Nicole van de Kar, Ria H.L.A. Philipsen, Maurice van Dael, Myrsini Kaforou, Victoria J. Wright, Jethro A. Herberg, Federico Martinon Torres, Michael Levin, Ronald de Groot, Alain J. van Gool, Dirk J. Lefeber, Hans J.C.T. Wessels, Marien I. de Jonge, Amina Abdulla, Christoph Aebi, Koen van Aerde, Rachel Agbeko, Philipp Agyeman, Umberto D’alessandro, Ladan Ali, Wynand Alkema, Karen Allen, Fernando Álvez González, Suzanne Anderson, Imran Ansari, Tasnim Araf, Tanja Avramoska, Bryan Baas, Natalija Bahovec, Cristina Balo Farto, Anda Balode, A.M. Barendregt, Ruth Barral-Arca, María Barreiro Castro, Arta Bārzdiņa, David Bath, Sebastian Bauchinger, Lucas Baumard, Hinrich Baumgart, Frances Baxter, Ashley Bell, Kathryn Bell, Xabier Bello, Evangelos Bellos, Martin Benesch, Mirian Ben García, Joshua Bennet, Christoph Berger, J.M. van den Berg, Sara Bernhard-Stirnemann, Sagida Bibi, Christoph Bidlingmaier, Alexander Binder, Vera Binder, Kalifa Bojang, Dorine M. Borensztajn, Ulrich von Both, Karen Brengel-Pesce, Bryan van den Broek, Judith Buschbeck, Leo Calvo-Bado, Sandra Carnota, Enitan D. Carrol, Michael J. Carter, Miriam Cebey-López, Samba Ceesay, Astrid Ceolotto, Adora Chan, Elizabeth Cocklin, Kalvin Collings, Stephen Crulley, Aubrey Cunnington, María José Curras-Tuala, Katharina Danhauser, Saffiatou Darboe, Sarah Darnell, Tisham De, Dārta Deksne, Kirsty Devine, Juan Emmanuel Dewez, Julia Dudley, Carlos Durán Suárez, Ernst Eber, Irini Eleftheriou, Marieke Emonts, Daniel Fabian, Tobias Feuchtinger, Katy Fidler, Colin Fink, A.M. van Furth, Rachel Galassini, Siegfried Gallistl, Luisa García Vicente, Dace Gardovska, J. Geissler, G.P.J.M. Gerrits, Eric Giannoni, Ilona van der Giessen, Alberto Gómez-Carballa, Jose Gómez Rial, Gunther Gores, Dagne Grāvele, Matthias Griese, Ilze Grope, Meeru Gurung, L. de Haan, Nikolaus Haas, Dominic Habgood-Coote, Nienke N. Hagedoorn, Harald Haidl, Shea Hamilton, Almuthe Hauer, J. Heidema, Ulrich Heininger, Stefanie Henriet, Jethro Herberg, Clive Hoggart, Susanne Hösele, Sara Hourmat, Christa Hude, Martijn Huijnen, Heather Jackson, Rebecca Jennings, Joanne Johnston, Ilse Jongerius, Rikke Jorgensen, Christian Kahlert, Rama Kandasamy, Matthias Kappler, Julia Keil, Markus Keldorfer, Dominic F. Kell, Eunjung Kim, Sharon King, Lieke Kloosterhuis, Daniela S. Kohlfürst, Benno Kohlmaier, Laura Kolberg, Mojca Kolnik, Larissa Krenn, Taco Kuijpers, M. van der Kuip, Pilar Leboráns Iglesias, Simon Leigh, Manuel Leitner, M. van Leur, Emma Lim, Naomi Lin, Ching-Chuan Liu, Sabine Löffler, Eberhard Lurz, Ian Maconochie, Christine Mackerness, François Mallet, Federico Martinón-Torres, Antonis Marmarinos, Alex Martin, Mike Martin, José María Martinón Sánchez, Nazareth Martinón-Torres, Paul McAlinden, Anne McDonnell, Sam McDonald, C.J. Miedema, Anija Meiere, Stephanie Menikou, G. van Mierlo, Alec Miners, Ravi Mistry, Henriëtte A. Moll, Marine Mommert, Belén Mosquera Pérez, David R. Murdoch, Sobia Mustafa, Giancarlo Natalucci, C. Neeleman, Karen Newall, Samuel Nichols, Tobias Niedrist, Anita Niederer-Loher, Ruud Nijman, Ieva Nokalna, Urzula Nora Urbāne, Gudrun Nordberg, C.C. Obihara, Daniel O'Connor, Wilma Oosthoek, Veronika Osterman, Alexandre Pachot, D. Pajkrt, Jacobo Pardo-Seco, Stéphane Paulus, Jana Pavāre, Ivonne Pena Paz, Salina Persand, Andreas Pfleger, Klaus Pfurtscheller, Ria Philipsen, Ailsa Pickering, Benjamin Pierce, Heidemarie Pilch, Lidia Piñeiro Rodríguez, Sara Pischedda, Tina Plankar Srovin, Marko Pokorn, Andrew J. Pollard, Lena Pölz, Klara M. Posfay-Barbe, Petra Prunk, Zanda Pučuka, Glorija Rajic, Aqeela Rashid, Lorenzo Redondo-Collazo, Christa Relly, Irene Rivero Calle, Sara Rey Vázquez, Mathew Rhodes, Vivien Richmond, Thomas Riedel, Anna RocaIsatou Sarr, Siegfried Rödl, Carmen Rodríguez-Tenreiro, Sam Romaine, Emily Rowlands, Miguel Sadiki Ora, Manfred G. Sagmeister, Momodou Saidykhan, Antonio Salas, Luregn J. Schlapbach, D. Schonenberg, Fatou Secka, Katrīna Selecka, Sonia Serén Fernández, Cristina Serén Trasorras, Priyen Shah, Ching-Fen Shen, Shrijana Shrestha, Aleksandra Sidorova, Andrea Skrabl-Baumgartner, Giselle D’Souza, Matthias Sperl, Evelien Sprenkeler, Nina A. Schweintzger, Laura Stampfer, Molly Stevens, Martin Stocker, Volker Strenger, Dace Svile, Kelly Syggelou, Maria Tambouratzi, Chantal Tan, Emma Tavliavini, Evelyn Thomson, Stephen Thorson, Holger Till, G.A. Tramper-Stranders, Andreas Trobisch, Maria Tsolia, Effua Usuf, Lucille Valentine, Clementien L. Vermont, Marisol Vilas Iglesias, Katarina Vincek, Marie Voice, Gabriella de Vries, Diane Wallia, Shih-Min Wang, Clare Wilson, Amanda Wood, Phil Woodsford, Victoria Wright, Marietta Xagorari, Shunmay Yeung, Joany Zachariasse, Dace Zavadska, Syed M.A. Zaman, Judith Zandstra, Werner Zenz, Christoph Zurl, and Manuela Zwerenz
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Health sciences ,Glycobiology ,Immunology ,Glycomics ,Science - Abstract
Summary: Mechanisms of infection and pathogenesis have predominantly been studied based on differential gene or protein expression. Less is known about posttranslational modifications, which are essential for protein functional diversity. We applied an innovative glycoproteomics method to study the systemic proteome-wide glycosylation in response to infection. The protein site-specific glycosylation was characterized in plasma derived from well-defined controls and patients. We found 3862 unique features, of which we identified 463 distinct intact glycopeptides, that could be mapped to more than 30 different proteins. Statistical analyses were used to derive a glycopeptide signature that enabled significant differentiation between patients with a bacterial or viral infection. Furthermore, supported by a machine learning algorithm, we demonstrated the ability to identify the causative pathogens based on the distinctive host blood plasma glycopeptide signatures. These results illustrate that glycoproteomics holds enormous potential as an innovative approach to improve the interpretation of relevant biological changes in response to infection.
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- 2023
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4. Osteoarticular Infections in Pediatric Hospitals in Europe: A Prospective Cohort Study From the EUCLIDS Consortium
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Andreas Trobisch, Nina A. Schweintzger, Daniela S. Kohlfürst, Manfred G. Sagmeister, Matthias Sperl, Andrea J. Grisold, Gebhard Feierl, Jethro A. Herberg, Enitan D. Carrol, Stephane C. Paulus, Marieke Emonts, Michiel van der Flier, Ronald de Groot, Miriam Cebey-López, Irene Rivero-Calle, Navin P. Boeddha, Paul-Michael Agapow, Fatou Secka, Suzanne T. Anderson, Uta Behrends, Uwe Wintergerst, Karl Reiter, Federico Martinon-Torres, Michael Levin, Werner Zenz, and The EUCLIDS consortium
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pediatric osteomyelitis ,pediatric septic arthritis ,Europe ,EUCLIDS ,S. aureus ,Pediatrics ,RJ1-570 - Abstract
BackgroundPediatric osteoarticular infections (POAIs) are serious diseases requiring early diagnosis and treatment.MethodsIn this prospective multicenter cohort study, children with POAIs were selected from the European Union Childhood Life-threatening Infectious Diseases Study (EUCLIDS) database to analyze their demographic, clinical, and microbiological data.ResultsA cohort of 380 patients with POAIs, 203 with osteomyelitis (OM), 158 with septic arthritis (SA), and 19 with both OM and SA, was analyzed. Thirty-five patients were admitted to the Pediatric Intensive Care Unit; out of these, six suffered from shock, one needed an amputation of the right foot and of four left toes, and two had skin transplantation. According to the Pediatric Overall Performance Score, 36 (10.5%) showed a mild overall disability, 3 (0.8%) a moderate, and 1 (0.2%) a severe overall disability at discharge. A causative organism was detected in 65% (247/380) of patients. Staphylococcus aureus (S. aureus) was identified in 57.1% (141/247) of microbiological confirmed cases, including 1 (0.7%) methicillin-resistant S. aureus (MRSA) and 6 (4.2%) Panton-Valentine leukocidin (PVL)-producing S. aureus, followed by Group A Streptococcus (18.2%) and Kingella kingae (8.9%). K. kingae and PVL production in S. aureus were less frequently reported than expected from the literature.ConclusionPOAIs are associated with a substantial morbidity in European children, with S. aureus being the major detected pathogen. In one-third of patients, no causative organism is identified. Our observations show an urgent need for the development of a vaccine against S. aureus and for the development of new microbiologic diagnostic guidelines for POAIs in European pediatric hospitals.
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- 2022
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5. Role and Diagnostic Performance of Host Epigenome in Respiratory Morbidity after RSV Infection: The EPIRESVi Study
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Sara Pischedda, Irene Rivero-Calle, Alberto Gómez-Carballa, Miriam Cebey-López, Ruth Barral-Arca, Jose Gómez-Rial, Jacobo Pardo-Seco, María-José Curras-Tuala, Sandra Viz-Lasheras, Xabier Bello, Ana B. Crujeiras, Angel Diaz-Lagares, María Teresa González-López, Federico Martinón-Torres, Antonio Salas, and GENDRES consortium
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RSV ,DNA methylation ,immune system ,respiratory sequelae ,recurrent wheezing ,asthma ,Immunologic diseases. Allergy ,RC581-607 - Abstract
BackgroundRespiratory syncytial virus (RSV) infection has been associated with the subsequent development of recurrent wheezing and asthma, although the mechanisms involved are still unknown. We investigate the role of epigenetics in the respiratory morbidity after infection by comparing methylation patterns from children who develop recurrent wheezing (RW-RSV), subsequent asthma (AS-RVS), and those experiencing complete recovery (CR-RSV).MethodsProspective, observational study of infants aged < 2 years with RSV respiratory infection admitted to hospital and followed-up after discharge for at least three years. According to their clinical course, patients were categorized into subgroups: RW-RSV (n = 36), AS-RSV (n = 9), and CR-RSV (n = 32). The DNA genome-wide methylation pattern was analyzed in whole blood samples, collected during the acute phase of the infection, using the Illumina Infinium Methylation EPIC BeadChip (850K CpG sites). Differences in methylation were determined through a linear regression model adjusted for age, gender and cell composition.ResultsPatients who developed respiratory sequelae showed a statistically significant higher proportion of NK and CD8T cells (inferred through a deconvolution approach) than those with complete recovery. We identified 5,097 significant differentially methylated positions (DMPs) when comparing RW-RSV and AS-RVS together against CR-RSV. Methylation profiles affect several genes involved in airway inflammation processes. The most significant DMPs were found to be hypomethylated in cases and therefore generally leading to overexpression of affected genes. The lead CpG position (cg24509398) falls at the gene body of EYA3 (P-value = 2.77×10-10), a tyrosine phosphatase connected with pulmonary vascular remodeling, a key process in the asthma pathology. Logistic regression analysis resulted in a diagnostic epigenetic signature of 3-DMPs (involving genes ZNF2698, LOC102723354 and RPL15/NKIRAS1) that allows to efficiently differentiate sequelae cases from CR-RSV patients (AUC = 1.00). Enrichment pathway analysis reveals the role of the cell cycle checkpoint (FDR P-value = 4.71×10-2), DNA damage (FDP-value = 2.53×10-2), and DNA integrity checkpoint (FDR P-value = 2.56×10-2) in differentiating sequelae from CR-RSV patients.ConclusionsEpigenetic mechanisms might play a fundamental role in the long-term sequelae after RSV infection, contributing to explain the different phenotypes observed.
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- 2022
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6. Differences between diabetic and non-diabetic patients with community-acquired pneumonia in primary care in Spain
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Loreto Arias Fernández, Jacobo Pardo Seco, Miriam Cebey-López, Ruth Gil Prieto, Irene Rivero-Calle, Federico Martinon-Torres, Ángel Gil de Miguel, on behalf of NEUMOEXPERTOS group, F. Martinón-Torres, D. Vargas, E. Mascarós, E. Redondo, J. L. Díaz-Maroto, M. Linares-Rufo, A. Gil, J. Molina, D. Ocaña, and I. Rivero-Calle
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Diabetes ,Community-acquired pneumonia ,Primary care ,Risk factors ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Diabetes is one of the underlying risk factors for developing community-acquired pneumonia (CAP). The high prevalence of diabetes among population and the rising incidence of this illness, converts it as an important disease to better control and manage, to prevent its secondary consequences as CAP. The objective of this research is to describe the characteristics of the patients with diabetes and the differences with the no diabetes who have had an episode of CAP in the context of the primary care field. Methods A retrospective, observational study in adult patients (> 18 years-old) who suffer from CAP and attended at primary care in Spain between 2009 and 2013 was developed using the Computerized Database for Pharmacoepidemiological Studies in Primary Care (BIFAP). We carried out a descriptive analysis of the first episodes of CAP, in patients with or without diabetes as comorbidity. Other morbidity (CVA, Anaemia, Arthritis, Asthma, Heart disease, Dementia, Depression, Dysphagia, Multiple sclerosis, Epilepsy, COPD, Liver disease, Arthrosis, Parkinson’s disease, Kidney disease, HIV) and life-style factors were also included in the study. Results A total of 51,185 patients were included in the study as they suffer from the first episode of CAP. Of these, 8012 had diabetes as comorbidity. There were differences between sex and age in patients with diabetes. Patients without diabetes were younger, and had less comorbidities including those related to lifestyles such as smoking, alcoholism, social and dental problems than patients with diabetes. Conclusions Patients who developed an episode of CAP with diabetes have more risk factors which could be reduced with an appropriate intervention, including vaccination to prevent successive CAP episodes and hospitalization. The burden of associated factors in these patients can produce an accumulation of risk. Health care professional should know this for treating and control these patients in order to avoid complications. Diabetes and those other risk factors associated could be reduced with an appropriate intervention, including vaccination to prevent the first and successive CAP episodes and the subsequent hospitalization in severe cases.
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- 2019
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7. Corrigendum: Case Report: Two Monochorionic Twins With a Critically Different Course of Progressive Osseous Heteroplasia
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Antonio José Justicia-Grande, Jose Gómez-Ríal, Irene Rivero-Calle, Sara Pischedda, María José Curras-Tuala, Alberto Gómez-Carballa, Miriam Cebey-López, Jacobo Pardo-Seco, Roberto Méndez-Gallart, María José Fernández-Seara, Antonio Salas, and Federico Martinón-Torres
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progressive osseous heteroplasia ,POH ,treatment ,genetic diseases ,monochorionic twins ,Pediatrics ,RJ1-570 - Published
- 2021
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8. Detectable A Disintegrin and Metalloproteinase With Thrombospondin Motifs-1 in Serum Is Associated With Adverse Outcome in Pediatric Sepsis
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Navin P. Boeddha, MD, PhD, Gertjan J. Driessen, MD, PhD, Nienke N. Hagedoorn, MD, Daniela S. Kohlfuerst, MD, Clive J. Hoggart, PhD, Angelique L. van Rijswijk, MSc, Ebru Ekinci, MD, Debby Priem, BSc, Luregn J. Schlapbach, MD, PhD, Jethro A. Herberg, MD, PhD, Ronald de Groot, MD, PhD, Suzanne T. Anderson, MD, PhD, Colin G. Fink, PhD, Enitan D. Carrol, MD, PhD, Michiel van der Flier, MD, PhD, Federico Martinón-Torres, MD, PhD, Michael Levin, MD, PhD, Frank W. Leebeek, MD, PhD, Werner Zenz, MD, PhD, Moniek P. M. de Maat, PhD, Jan A. Hazelzet, MD, PhD, Marieke Emonts, MD, PhD, Willem A. Dik, PhD, on behalf of the EUCLIDS consortium, Michael Levin, Lachlan Coin, Stuart Gormley, Shea Hamilton, Jethro Herberg, Bernardo Hourmat, Clive Hoggart, Myrsini Kaforou, Vanessa Sancho-Shimizu, Victoria Wright, Amina Abdulla, Paul Agapow, Maeve Bartlett, Evangelos Bellos, Hariklia Eleftherohorinou, Rachel Galassini, David Inwald, Meg Mashbat, Stefanie Menikou, Sobia Mustafa, Simon Nadel, Rahmeen Rahman, Clare Thakker, S Bokhandi, Sue Power, Heather Barham, N Pathan, Jenna Ridout, Deborah White, Sarah Thurston, S Faust, S Patel, Jenni McCorkell, P Davies, Lindsey Crate, Helen Navarra, Stephanie Carter, R Ramaiah, Rekha Patel, Catherine Tuffrey, Andrew Gribbin, Sharon McCready, Mark Peters, Katie Hardy, Fran Standing, Lauren O’Neill, Eugenia Abelake, Akash Deep, Eniola Nsirim, A Pollard, Louise Willis, Zoe Young, C Royad, Sonia White, PM Fortune, Phil Hudnott, Federico Martinón-Torres, Antonio Salas, Fernando Álvez González, Ruth Barral-Arca, Miriam Cebey-López, María José CurrasTuala, Natalia García, Luisa García Vicente, Alberto Gómez-Carballa, Jose Gómez Rial, Andrea Grela Beiroa, Antonio Justicia Grande, Pilar Leboráns Iglesias, Alba Elena Martínez Santos, Nazareth Martinón-Torres, José María Martinón Sánchez, Beatriz Morillo Gutiérrez, Belén Mosquera Pérez, Pablo Obando Pacheco, Jacobo Pardo-Seco, Sara Pischedda, Irene Rivero Calle, Carmen Rodríguez-Tenreiro, Lorenzo Redondo-Collazo, Antonio Salas Ellacuriaga, Sonia Serén Fernández, María del Sol Porto Silva, Ana Vega, Lucía Vilanova Trillo, Susana Beatriz Reyes, María Cruz León León, Álvaro Navarro Mingorance, Xavier Gabaldó Barrios, Eider Oñate Vergara, Andrés Concha Torre, Ana Vivanco, Reyes Fernández, Francisco Giménez Sánchez, Miguel Sánchez Forte, Pablo Rojo, J.Ruiz Contreras, Alba Palacios, Cristina Epalza Ibarrondo, Elizabeth Fernández Cooke, Marisa Navarro, Cristina Álvarez Álvarez, María José Lozano, Eduardo Carreras, Sonia Brió Sanagustín, Olaf Neth, Mª del Carmen Martínez Padilla, Luis Manuel Prieto Tato, Sara Guillén, Laura Fernández Silveira, David Moreno, R. de Groot, A.M. Tutu van Furth, M. van der Flier, N.P. Boeddha, G.J.A. Driessen, M. Emonts, J.A. Hazelzet, T.W. Kuijpers, D. Pajkrt, E.A.M. Sanders, D. van de Beek, A. van der Ende, H.L.A. Philipsen, A.O.A. Adeel, M.A. Breukels, D.M.C. Brinkman, C.C.M.M. de Korte, E. de Vries, W.J. de Waal, R. Dekkers, A. Dings-Lammertink, R.A. Doedens, A.E. Donker, M. Dousma, T.E. Faber, G.P.J.M. Gerrits, J.A.M. Gerver, J. Heidema, J. Homan-van der Veen, M.A.M. Jacobs, N.J.G. Jansen, P. Kawczynski, K. Klucovska, M.C.J. Kneyber, Y. Koopman-Keemink, V.J. Langenhorst, J. Leusink, B.F. Loza, I.T. Merth, C.J. Miedema, C. Neeleman, J.G. Noordzij, C.C. Obihara, A.L.T. van Overbeek – van Gils, G.H. Poortman, S.T. Potgieter, J. Potjewijd, P.P.R. Rosias, T. Sprong, G.W. ten Tussher, B.J. Thio, G.A. Tramper-Strander, M. van Deuren, H. van der Meer, A.J.M. van Kuppevelt, A.M. van Wermeskerken, W.A. Verwijs, T.F.W. Wolfs, Luregn J Schlapbach, Philipp Agyeman, Christoph Aebi, Eric Giannoni, Martin Stocker, Klara M Posfay-Barbe, Ulrich Heininger, Sara Bernhard-Stirnemann, Anita Niederer-Loher, Christian Kahlert, Paul Hasters, Christa Relly, Walter Baer, Christoph Berger, Enitan Carrol, Stéphane Paulus, Hannah Frederick, Rebecca Jennings, Joanne Johnston, Rhian Kenwright, Colin G Fink, Elli Pinnock, Marieke Emonts, Rachel Agbeko, Suzanne Anderson, Fatou Secka, Kalifa Bojang, Isatou Sarr, Ngane Kebbeh, Gibbi Sey, Momodou Saidykhan, Fatoumatta Cole, Gilleh Thomas, Martin Antonio, Werner Zenz, Daniela S. Klobassa, Alexander Binder, Nina A. Schweintzger, Manfred Sagmeister, Hinrich Baumgart, Markus Baumgartner, Uta Behrends, Ariane Biebl, Robert Birnbacher, Jan-Gerd Blanke, Carsten Boelke, Kai Breuling, Jürgen Brunner, Maria Buller, Peter Dahlem, Beate Dietrich, Ernst Eber, Johannes Elias, Josef Emhofer, Rosa Etschmaier, Sebastian Farr, Ylenia Girtler, Irina Grigorow, Konrad Heimann, Ulrike Ihm, Zdenek Jaros, Hermann Kalhoff, Wilhelm Kaulfersch, Christoph Kemen, Nina Klocker, Bernhard Köster, Benno Kohlmaier, Eleni Komini, Lydia Kramer, Antje Neubert, Daniel Ortner, Lydia Pescollderungg, Klaus Pfurtscheller, Karl Reiter, Goran Ristic, Siegfried Rödl, Andrea Sellner, Astrid Sonnleitner, Matthias Sperl, Wolfgang Stelzl, Holger Till, Andreas Trobisch, Anne Vierzig, Ulrich Vogel, Christina Weingarten, Stefanie Welke, Andreas Wimmer, Uwe Wintergerst, Daniel Wüller, Andrew Zaunschirm, Ieva Ziuraite, and Veslava Žukovskaja
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Medical emergencies. Critical care. Intensive care. First aid ,RC86-88.9 - Abstract
IMPORTANCE:. A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 is hypothesized to play a role in the pathogenesis of invasive infection, but studies in sepsis are lacking. OBJECTIVES:. To study A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 protein level in pediatric sepsis and to study the association with outcome. DESIGN:. Data from two prospective cohort studies. SETTING AND PARTICIPANTS:. Cohort 1 is from a single-center study involving children admitted to PICU with meningococcal sepsis (samples obtained at three time points). Cohort 2 includes patients from a multicenter study involving children admitted to the hospital with invasive bacterial infections of differing etiologies (samples obtained within 48 hr after hospital admission). MAIN OUTCOMES AND MEASURES:. Primary outcome measure was mortality. Secondary outcome measures were PICU-free days at day 28 and hospital length of stay. RESULTS:. In cohort 1 (n = 59), nonsurvivors more frequently had A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 levels above the detection limit than survivors at admission to PICU (8/11 [73%] and 6/23 [26%], respectively; p = 0.02) and at t = 24 hours (2/3 [67%] and 3/37 [8%], respectively; p = 0.04). In cohort 2 (n = 240), A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 levels in patients within 48 hours after hospital admission were more frequently above the detection limit than in healthy controls (110/240 [46%] and 14/64 [22%], respectively; p = 0.001). Nonsurvivors more often had detectable A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 levels than survivors (16/21 [76%] and 94/219 [43%], respectively; p = 0.003), which was mostly attributable to patients with Neisseria meningitidis. CONCLUSIONS AND RELEVANCE:. In children with bacterial infection, detection of A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 within 48 hours after hospital admission is associated with death, particularly in meningococcal sepsis. Future studies should confirm the prognostic value of A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 and should study pathophysiologic mechanisms.
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- 2021
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9. Case Report: Two Monochorionic Twins With a Critically Different Course of Progressive Osseous Heteroplasia
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Antonio José Justicia-Grande, Jose Gómez-Ríal, Irene Rivero-Calle, Sara Pischedda, María José Curras-Tuala, Alberto Gómez-Carballa, Miriam Cebey-López, Jacobo Pardo-Seco, Roberto Méndez-Gallart, María José Fernández-Seara, Antonio Salas, and Federico Martinón-Torres
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progressive osseous heteroplasia ,POH ,treatment ,genetic diseases ,monochorionic twins ,Pediatrics ,RJ1-570 - Abstract
Progressive osseous heteroplasia (POH; OMIM 166350) is a rare autosomal-dominant genetic disorder in which extra-skeletal bone forms within skin and muscle tissue. POH is one of the clinical manifestations of an inactivating mutation in the GNAS gene. GNAS gene alterations are difficult matter to address, as GNAS alleles show genetic imprinting and produce several transcript products, and the same mutation may lead to strikingly different phenotypes. Also, most of the publications concerning POH patients are either clinical depictions of a case (or a case series), descriptions of their genetic background, or a tentative correlation of both clinical and molecular findings. Treatment for POH is rarely addressed, and POH still lacks therapeutic options. We describe a unique case of POH in two monochorionic twins, who presented an almost asymptomatic vs. the severe clinical course, despite sharing the same mutation and genetic background. We also report the results of the therapeutic interventions currently available for heterotopic ossification in the patient with the severe course. This article not only critically supports the assumption that the POH course is strongly influenced by factors beyond genetic background but also remarks the lack of options for patients suffering an orphan disease, even after testing drugs with promising in vitro results.
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- 2021
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10. Host Transcriptomic Response Following Administration of Rotavirus Vaccine in Infants’ Mimics Wild Type Infection
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Alberto Gómez-Carballa, Ruth Barral-Arca, Miriam Cebey-López, Maria José Currás-Tuala, Sara Pischedda, José Gómez-Rial, Dominic Habgood-Coote, Jethro A. Herberg, Myrsini Kaforou, Federico Martinón-Torres, and Antonio Salas
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biomarkers ,RNA-seq ,transcriptomics ,vaccination ,miRNA ,rotavirus ,Immunologic diseases. Allergy ,RC581-607 - Abstract
BackgroundRotavirus (RV) is an enteric pathogen that has devastating impact on childhood morbidity and mortality worldwide. The immunologic mechanism underlying the protection achieved after RV vaccination is not yet fully understood.MethodsWe compared the transcriptome of children affected by community-acquired RV infection and children immunized with a live attenuated RV vaccine (RotaTeq®).ResultsRV vaccination mimics the wild type infection causing similar changes in children’s transcriptome, including transcripts associated with cell cycle, diarrhea, nausea, vomiting, intussusception, and abnormal morphology of midgut. A machine learning approach allowed to detect a combination of nine-transcripts that differentiates vaccinated from convalescent-naturally infected children (AUC: 90%; 95%CI: 70–100) and distinguishes between acute-infected and healthy control children (in both cases, AUC: 100%; 95%CI: 100–100). We identified a miRNA hsa-mir-149 that seems to play a role in the host defense against viral pathogens and may have an antiviral role.DiscussionOur findings might shed further light in the understanding of RV infection, its functional link to intussusception causes, as well as guide development of antiviral treatments and safer and more effective vaccines. The nine-transcript signature may constitute a marker of vaccine protection and helps to differentiate vaccinated from naturally infected or susceptible children.
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- 2021
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11. Increased Serum Levels of sCD14 and sCD163 Indicate a Preponderant Role for Monocytes in COVID-19 Immunopathology
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Jose Gómez-Rial, Maria José Currás-Tuala, Irene Rivero-Calle, Alberto Gómez-Carballa, Miriam Cebey-López, Carmen Rodríguez-Tenreiro, Ana Dacosta-Urbieta, Carmen Rivero-Velasco, Nuria Rodríguez-Núñez, Rocio Trastoy-Pena, Javier Rodríguez-García, Antonio Salas, and Federico Martinón-Torres
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COVID-19 ,monocyte ,sCD14 ,sCD163 ,immunopathology ,Immunologic diseases. Allergy ,RC581-607 - Abstract
BackgroundEmerging evidence indicates a potential role for monocytes in COVID-19 immunopathology. We investigated two soluble markers of monocyte activation, sCD14 and sCD163, in COVID-19 patients, with the aim of characterizing their potential role in monocyte-macrophage disease immunopathology. To the best of our knowledge, this is the first study of its kind.MethodsFifty-nine SARS-Cov-2 positive hospitalized patients, classified according to ICU or non-ICU admission requirement, were prospectively recruited and analyzed by ELISA for levels of sCD14 and sCD163, along with other laboratory parameters, and compared to a healthy control group.ResultssCD14 and sCD163 levels were significantly higher among COVID-19 patients, independently of ICU admission requirement, compared to the control group. We found a significant correlation between sCD14 levels and other inflammatory markers, particularly Interleukin-6, in the non-ICU patients group. sCD163 showed a moderate positive correlation with the time lapsed from admission to sampling, independently of severity group. Treatment with corticoids showed an interference with sCD14 levels, whereas hydroxychloroquine and tocilizumab did not.ConclusionsMonocyte-macrophage activation markers are increased and correlate with other inflammatory markers in SARS-Cov-2 infection, in association to hospital admission. These data suggest a preponderant role for monocyte-macrophage activation in the development of immunopathology of COVID-19 patients.
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- 2020
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12. Mortality and morbidity in community-acquired sepsis in European pediatric intensive care units: a prospective cohort study from the European Childhood Life-threatening Infectious Disease Study (EUCLIDS)
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Navin P. Boeddha, Luregn J. Schlapbach, Gertjan J. Driessen, Jethro A. Herberg, Irene Rivero-Calle, Miriam Cebey-López, Daniela S. Klobassa, Ria Philipsen, Ronald de Groot, David P. Inwald, Simon Nadel, Stéphane Paulus, Eleanor Pinnock, Fatou Secka, Suzanne T. Anderson, Rachel S. Agbeko, Christoph Berger, Colin G. Fink, Enitan D. Carrol, Werner Zenz, Michael Levin, Michiel van der Flier, Federico Martinón-Torres, Jan A. Hazelzet, Marieke Emonts, and on behalf of the EUCLIDS consortium
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Bacteremia ,Meningococcal infections ,Pneumococcal infections ,Mortality ,Morbidity ,Medical emergencies. Critical care. Intensive care. First aid ,RC86-88.9 - Abstract
Abstract Background Sepsis is one of the main reasons for non-elective admission to pediatric intensive care units (PICUs), but little is known about determinants influencing outcome. We characterized children admitted with community-acquired sepsis to European PICUs and studied risk factors for mortality and disability. Methods Data were collected within the collaborative Seventh Framework Programme (FP7)-funded EUCLIDS study, which is a prospective multicenter cohort study aiming to evaluate genetic determinants of susceptibility and/or severity in sepsis. This report includes 795 children admitted with community-acquired sepsis to 52 PICUs from seven European countries between July 2012 and January 2016. The primary outcome measure was in-hospital death. Secondary outcome measures were PICU-free days censured at day 28, hospital length of stay, and disability. Independent predictors were identified by multivariate regression analysis. Results Patients most commonly presented clinically with sepsis without a source (n = 278, 35%), meningitis/encephalitis (n = 182, 23%), or pneumonia (n = 149, 19%). Of 428 (54%) patients with confirmed bacterial infection, Neisseria meningitidis (n = 131, 31%) and Streptococcus pneumoniae (n = 78, 18%) were the main pathogens. Mortality was 6% (51/795), increasing to 10% in the presence of septic shock (45/466). Of the survivors, 31% were discharged with disability, including 24% of previously healthy children who survived with disability. Mortality and disability were independently associated with S. pneumoniae infections (mortality OR 4.1, 95% CI 1.1–16.0, P = 0.04; disability OR 5.4, 95% CI 1.8–15.8, P
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- 2018
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13. Identification of a Minimal 3-Transcript Signature to Differentiate Viral from Bacterial Infection from Best Genome-Wide Host RNA Biomarkers: A Multi-Cohort Analysis
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Alberto Gómez-Carballa, Ruth Barral-Arca, Miriam Cebey-López, Xabier Bello, Jacobo Pardo-Seco, Federico Martinón-Torres, and Antonio Salas
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RNA ,RNAseq ,microarrays ,transcriptome ,transcriptomic biomarkers ,RNA signature ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
The fight against the spread of antibiotic resistance is one of the most important challenges facing health systems worldwide. Given the limitations of current diagnostic methods, the development of fast and accurate tests for the diagnosis of viral and bacterial infections would improve patient management and treatment, as well as contribute to reducing antibiotic misuse in clinical settings. In this scenario, analysis of host transcriptomics constitutes a promising target to develop new diagnostic tests based on the host-specific response to infections. We carried out a multi-cohort meta-analysis of blood transcriptomic data available in public databases, including 11 different studies and 1209 samples from virus- (n = 695) and bacteria- (n = 514) infected patients. We applied a Parallel Regularized Regression Model Search (PReMS) on a set of previously reported genes that distinguished viral from bacterial infection to find a minimum gene expression bio-signature. This strategy allowed us to detect three genes, namely BAFT, ISG15 and DNMT1, that clearly differentiate groups of infection with high accuracy (training set: area under the curve (AUC) 0.86 (sensitivity: 0.81; specificity: 0.87); testing set: AUC 0.87 (sensitivity: 0.82; specificity: 0.86)). BAFT and ISG15 are involved in processes related to immune response, while DNMT1 is related to the preservation of methylation patterns, and its expression is modulated by pathogen infections. We successfully tested this three-transcript signature in the 11 independent studies, demonstrating its high performance under different scenarios. The main advantage of this three-gene signature is the low number of genes needed to differentiate both groups of patient categories.
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- 2021
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14. RNA-Seq Data-Mining Allows the Discovery of Two Long Non-Coding RNA Biomarkers of Viral Infection in Humans
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Ruth Barral-Arca, Alberto Gómez-Carballa, Miriam Cebey-López, María José Currás-Tuala, Sara Pischedda, Sandra Viz-Lasheras, Xabier Bello, Federico Martinón-Torres, and Antonio Salas
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biomarkers ,RNA-seq ,lncRNA ,virus ,machine learning ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
There is a growing interest in unraveling gene expression mechanisms leading to viral host invasion and infection progression. Current findings reveal that long non-coding RNAs (lncRNAs) are implicated in the regulation of the immune system by influencing gene expression through a wide range of mechanisms. By mining whole-transcriptome shotgun sequencing (RNA-seq) data using machine learning approaches, we detected two lncRNAs (ENSG00000254680 and ENSG00000273149) that are downregulated in a wide range of viral infections and different cell types, including blood monocluclear cells, umbilical vein endothelial cells, and dermal fibroblasts. The efficiency of these two lncRNAs was positively validated in different viral phenotypic scenarios. These two lncRNAs showed a strong downregulation in virus-infected patients when compared to healthy control transcriptomes, indicating that these biomarkers are promising targets for infection diagnosis. To the best of our knowledge, this is the very first study using host lncRNAs biomarkers for the diagnosis of human viral infections.
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- 2020
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15. A Meta-Analysis of Multiple Whole Blood Gene Expression Data Unveils a Diagnostic Host-Response Transcript Signature for Respiratory Syncytial Virus
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Ruth Barral-Arca, Alberto Gómez-Carballa, Miriam Cebey-López, Xabier Bello, Federico Martinón-Torres, and Antonio Salas
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meta-analysis ,rna ,transcriptomic ,rsv ,respiratory syncytial virus ,array ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Respiratory syncytial virus (RSV) is one of the major causes of acute lower respiratory tract infection worldwide. The absence of a commercial vaccine and the limited success of current therapeutic strategies against RSV make further research necessary. We used a multi-cohort analysis approach to investigate host transcriptomic biomarkers and shed further light on the molecular mechanism underlying RSV-host interactions. We meta-analyzed seven transcriptome microarray studies from the public Gene Expression Omnibus (GEO) repository containing a total of 922 samples, including RSV, healthy controls, coronaviruses, enteroviruses, influenzas, rhinoviruses, and coinfections, from both adult and pediatric patients. We identified > 1500 genes differentially expressed when comparing the transcriptomes of RSV-infected patients against healthy controls. Functional enrichment analysis showed several pathways significantly altered, including immunologic response mediated by RSV infection, pattern recognition receptors, cell cycle, and olfactory signaling. In addition, we identified a minimal 17-transcript host signature specific for RSV infection by comparing transcriptomic profiles against other respiratory viruses. These multi-genic signatures might help to investigate future drug targets against RSV infection.
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- 2020
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16. Does Viral Co-Infection Influence the Severity of Acute Respiratory Infection in Children?
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Miriam Cebey-López, Jethro Herberg, Jacobo Pardo-Seco, Alberto Gómez-Carballa, Nazareth Martinón-Torres, Antonio Salas, José María Martinón-Sánchez, Antonio Justicia, Irene Rivero-Calle, Edward Sumner, Colin Fink, Federico Martinón-Torres, and GENDRES network
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Medicine ,Science - Abstract
BACKGROUND:Multiple viruses are often detected in children with respiratory infection but the significance of co-infection in pathogenesis, severity and outcome is unclear. OBJECTIVES:To correlate the presence of viral co-infection with clinical phenotype in children admitted with acute respiratory infections (ARI). METHODS:We collected detailed clinical information on severity for children admitted with ARI as part of a Spanish prospective multicenter study (GENDRES network) between 2011-2013. A nested polymerase chain reaction (PCR) approach was used to detect respiratory viruses in respiratory secretions. Findings were compared to an independent cohort collected in the UK. RESULTS:204 children were recruited in the main cohort and 97 in the replication cohort. The number of detected viruses did not correlate with any markers of severity. However, bacterial superinfection was associated with increased severity (OR: 4.356; P-value = 0.005), PICU admission (OR: 3.342; P-value = 0.006), higher clinical score (1.988; P-value = 0.002) respiratory support requirement (OR: 7.484; P-value < 0.001) and longer hospital length of stay (OR: 1.468; P-value < 0.001). In addition, pneumococcal vaccination was found to be a protective factor in terms of degree of respiratory distress (OR: 2.917; P-value = 0.035), PICU admission (OR: 0.301; P-value = 0.011), lower clinical score (-1.499; P-value = 0.021) respiratory support requirement (OR: 0.324; P-value = 0.016) and oxygen necessity (OR: 0.328; P-value = 0.001). All these findings were replicated in the UK cohort. CONCLUSION:The presence of more than one virus in hospitalized children with ARI is very frequent but it does not seem to have a major clinical impact in terms of severity. However bacterial superinfection increases the severity of the disease course. On the contrary, pneumococcal vaccination plays a protective role.
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- 2016
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17. Development and Validation of a New Clinical Scale for Infants with Acute Respiratory Infection: The ReSVinet Scale.
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Antonio José Justicia-Grande, Jacobo Pardo-Seco, Miriam Cebey-López, Lucía Vilanova-Trillo, Alberto Gómez-Carballa, Irene Rivero-Calle, María Puente-Puig, Carmen Curros-Novo, José Gómez-Rial, Antonio Salas, José María Martinón-Sánchez, Lorenzo Redondo-Collazo, Carmen Rodríguez-Tenreiro, Federico Martinón-Torres, and Respiratory Syncytial Virus network (ReSVinet)
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Medicine ,Science - Abstract
BACKGROUND AND AIMS:A properly validated scoring system allowing objective categorization of infants with acute respiratory infections (ARIs), avoiding the need for in-person assessment and that could also be used by non-health professionals is currently not available. We aimed to develop a new clinical assessment scale meeting these specifications. METHODS:We designed a clinical scale (ReSVinet scale) based on seven parameters (feeding intolerance, medical intervention, respiratory difficulty, respiratory frequency, apnoea, general condition, fever) that were assigned different values (from 0 to 3) for a total of 20 points.170 children under two years of age with ARI were assessed independently by three pediatricians using this scale. Parents also evaluated their offspring with an adapted version of the scale in a subset of 61 cases. The scale was tested for internal consistency (Cronbach's alpha), Pearson correlation coefficient for the items in the scale, inter-observer reliability (kappa index) and floor-ceiling effect. RESULTS:Internal consistency was good for all the observers, with the lowest Cronbach's alpha being 0.72. There was a strong correlation between the investigators (r-value ranged 0.76-0.83) and also between the results obtained by the parents and the investigators(r = 0.73). Light's kappa for the observations of the three investigators was 0.74. Weighted kappa in the group evaluated by the parents was 0.73. The final score was correlated with length of hospital stay, PICU admission and Wood-Downes Score. CONCLUSIONS:The ReSVinet scale may be useful and reliable in the evaluation of infants with ARI, particularly acute bronchiolitis, even with data obtained from medical records and when employed by parents. Although further studies are necessary, ReSVinet scale already complies with more score validation criteria than the vast majority of the alternatives currently available and used in the clinical practice.
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- 2016
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18. Bacteremia in Children Hospitalized with Respiratory Syncytial Virus Infection.
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Miriam Cebey-López, Jacobo Pardo-Seco, Alberto Gómez-Carballa, Nazareth Martinón-Torres, José María Martinón-Sánchez, Antonio Justicia-Grande, Irene Rivero-Calle, Elli Pinnock, Antonio Salas, Colin Fink, Federico Martinón-Torres, and GENDRES network
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Medicine ,Science - Abstract
The risk of bacteremia is considered low in children with acute bronchiolitis. However the rate of occult bacteremia in infants with RSV infection is not well established. The aim was to determine the actual rate and predictive factors of bacteremia in children admitted to hospital due to confirmed RSV acute respiratory illness (ARI), using both conventional culture and molecular techniques.A prospective multicenter study (GENDRES-network) was conducted between 2011-2013 in children under the age of two admitted to hospital because of an ARI. Among those RSV-positive, bacterial presence in blood was assessed using PCR for Meningococcus, Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus pyogenes, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus, in addition to conventional cultures.66 children with positive RSV respiratory illness were included. In 10.6% patients, bacterial presence was detected: H. influenzae (n = 4) and S. pneumoniae (n = 2). In those patients with bacteremia, there was a previous suspicion of bacterial superinfection and had received empirical antibiotic treatment 6 out of 7 (85.7%) patients. There were significant differences in terms of severity between children with positive bacterial PCR and those with negative results: PICU admission (100% vs. 50%, P-value = 0.015); respiratory support necessity (100% vs. 18.6%, P-value < 0.001); Wood-Downes score (mean = 8.7 vs. 4.8 points, P-value < 0.001); GENVIP scale (mean = 17 vs. 10.1, P-value < 0.001); and length of hospitalization (mean = 12.1 vs. 7.5 days, P-value = 0.007).Bacteremia is not frequent in infants hospitalized with RSV respiratory infection, however, it should be considered in the most severe cases.
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- 2016
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19. Viral Co-Infections in Pediatric Patients Hospitalized with Lower Tract Acute Respiratory Infections.
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Miriam Cebey-López, Jethro Herberg, Jacobo Pardo-Seco, Alberto Gómez-Carballa, Nazareth Martinón-Torres, Antonio Salas, José María Martinón-Sánchez, Stuart Gormley, Edward Sumner, Colin Fink, Federico Martinón-Torres, and GENDRES network
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Medicine ,Science - Abstract
Molecular techniques can often reveal a broader range of pathogens in respiratory infections. We aim to investigate the prevalence and age pattern of viral co-infection in children hospitalized with lower tract acute respiratory infection (LT-ARI), using molecular techniques.A nested polymerase chain reaction approach was used to detect Influenza (A, B), metapneumovirus, respiratory syncytial virus (RSV), parainfluenza (1-4), rhinovirus, adenovirus (A-F), bocavirus and coronaviruses (NL63, 229E, OC43) in respiratory samples of children with acute respiratory infection prospectively admitted to any of the GENDRES network hospitals between 2011-2013. The results were corroborated in an independent cohort collected in the UK.A total of 204 and 97 nasopharyngeal samples were collected in the GENDRES and UK cohorts, respectively. In both cohorts, RSV was the most frequent pathogen (52.9% and 36.1% of the cohorts, respectively). Co-infection with multiple viruses was found in 92 samples (45.1%) and 29 samples (29.9%), respectively; this was most frequent in the 12-24 months age group. The most frequently observed co-infection patterns were RSV-Rhinovirus (23 patients, 11.3%, GENDRES cohort) and RSV-bocavirus / bocavirus-influenza (5 patients, 5.2%, UK cohort).The presence of more than one virus in pediatric patients admitted to hospital with LT-ARI is very frequent and seems to peak at 12-24 months of age. The clinical significance of these findings is unclear but should warrant further analysis.
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- 2015
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20. A multi-tissue study of immune gene expression profiling highlights the key role of the nasal epithelium in COVID-19 severity
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Alberto Gómez-Carballa, Irene Rivero-Calle, Jacobo Pardo-Seco, José Gómez-Rial, Carmen Rivero-Velasco, Nuria Rodríguez-Núñez, Gema Barbeito-Castiñeiras, Hugo Pérez-Freixo, Miriam Cebey-López, Ruth Barral-Arca, Carmen Rodriguez-Tenreiro, Ana Dacosta-Urbieta, Xabier Bello, Sara Pischedda, María José Currás-Tuala, Sandra Viz-Lasheras, Federico Martinón-Torres, Antonio Salas, Aguilera Guirao Antonio, Álvarez Escudero Julián, Antela López Antonio, Barbeito Castiñeiras Gema, Bello Paderne Xabier, Ben García Miriam, Carral García María Victoria, Cebey López Miriam, Coira Nieto Amparo, Conde Pájaro Mónica, Costa Alcalde José Javier, Currás Tuala María José, Dacosta Urbieta Ana Isabel, Díaz Esteban Blanca, Domínguez Santalla María Jesús, Fernández Pérez Cristina, Fernández Villaverde Juan, Galbán Rodríguez Cristóbal, García Allut José Luis, García Vicente Luisa, Giráldez Vázquez Elena, Gómez Carballa Alberto, Gómez Rial José, González Barcala Francisco Javier, Guerra Liñares Beatriz, Leboráns Iglesias Pilar, Lence Massa Beatriz, López Franco Montserrat, López Lago Ana, Martinón-Torres Federico, Navarro De la Cruz Daniel, Núñez Masid Eloína, Ortolá Devesa Juan Bautista, Pardo Seco Jacobo, Pazo Núñez María, Pérez del Molino Bernal Marisa, Pérez Freixo Hugo, Piñeiro Rodríguez Lidia, Pischedda Sara, Portela Romero Manuel, Pose Reino Antonio, Prada Hervella Gloria María, Queiro Verdes Teresa, Redondo Collazo Lorenzo, Regueiro Casuso Patricia, Rey García Susana, Rey Vázquez Sara, Riveiro Blanco Vanessa, Rivero Calle Irene, Rivero Velasco Carmen, Rodríguez Núñez Nuria, Rodríguez-Tenreiro Sánchez Carmen, Saborido Paz Eva, Sadiki Orayyou José Miguel, Saito Villanueva Carla, Serén Fernández Sonia, Souto Sanmartín Pablo, Taboada Muñiz Manuel, Trastoy Pena Rocío, Treviño Castellano Mercedes, Valdés Cuadrado Luis, Varela García Pablo, Vilas Iglesias María Soledad, Viz Lasheras Sandra, Ferreiro-Iglesias Rocio, null Bastón-Rey iria, Calviño-Suárez Cristina, and Universidade de Santiago de Compostela. Departamento de Ciencias Forenses, Anatomía Patolóxica, Xinecoloxía e Obstetricia, e Pediatría
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SARS-CoV-2 ,Gene Expression Profiling ,COVID-19 ,Multi-tissue ,COVID-19 severity ,Biochemistry ,Antiviral Agents ,Immunity, Innate ,Co-expression analysis ,Nasal Mucosa ,Pathways analysis ,Humans ,Gene expression ,Immune response ,Differential expression analysis ,Biomarkers ,General Environmental Science - Abstract
Coronavirus Disease-19 (COVID-19) symptoms range from mild to severe illness; the cause for this differential response to infection remains unknown. Unravelling the immune mechanisms acting at different levels of the colonization process might be key to understand these differences. We carried out a multi-tissue (nasal, buccal and blood; n = 156) gene expression analysis of immune-related genes from patients affected by different COVID-19 severities, and healthy controls through the nCounter technology. Mild and asymptomatic cases showed a powerful innate antiviral response in nasal epithelium, characterized by activation of interferon (IFN) pathway and downstream cascades, successfully controlling the infection at local level. In contrast, weak macrophage/monocyte driven innate antiviral response and lack of IFN signalling activity were present in severe cases. Consequently, oral mucosa from severe patients showed signals of viral activity, cell arresting and viral dissemination to the lower respiratory tract, which ultimately could explain the exacerbated innate immune response and impaired adaptative immune responses observed at systemic level. Results from saliva transcriptome suggest that the buccal cavity might play a key role in SARS-CoV-2 infection and dissemination in patients with worse prognosis. Co-expression network analysis adds further support to these findings, by detecting modules specifically correlated with severity involved in the abovementioned biological routes; this analysis also provides new candidate genes that might be tested as biomarkers in future studies. We also found tissue specific severity-related signatures mainly represented by genes involved in the innate immune system and cytokine/chemokine signalling. Local immune response could be key to determine the course of the systemic response and thus COVID-19 severity. Our findings provide a framework to investigate severity host gene biomarkers and pathways that might be relevant to diagnosis, prognosis, and therapy This study received support from Instituto de Salud Carlos III (ISCIII): GePEM (PI16/01478/Cofinanciado FEDER; A.S.), DIAVIR (DTS19/00049/Cofinanciado FEDER, A.S.), Resvi-Omics (PI19/01039/Cofinanciado FEDER, A.S.), ReSVinext (PI16/01569/Cofinanciado FEDER, F.M.T.), Enterogen (PI19/01090/Cofinanciado FEDER, F.M.T.); Agencia Gallega para la Gestión del Conocimiento en Salud (ACIS): BI-BACVIR (PRIS-3, A.S.), and CovidPhy (SA 304 C, A.S.); Agencia Gallega de Innovación (GAIN): Grupos con Potencial de Crecimiento (IN607B 2020/08, A.S.), GEN-COVID (IN845D 2020/23, F.M.T.); Framework Partnership Agreement between the Consellería de Sanidad de la XUNTA de Galicia and GENVIP-IDIS - 2021–2024 (SERGAS-IDIS march 2021); and consorcio Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CB21/06/00103; F.M.T.). We also thank Aida Freire Valls from Nanostring for her support SI
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- 2022
21. A multi-tissue study of immune gene expression profiling highlights the key role of the nasal epithelium in COVID-19 severity
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Luis Valdés, Irene Rivero Calle, Alberto Gómez-Carballa, María José Currás Tuala, and Miriam Cebey-López
- Abstract
BackgroundCOVID-19 symptoms range from mild to severe illness; the cause for this differential response to infection remains unknown. Unravelling the immune mechanisms acting at different levels of the colonization process might be key to understand these differences.Methods and findingsWe carried out a multi-tissue (nasal, buccal and blood; n = 156) gene expression analysis of immune-related genes from patients affected by different COVID-19 severities, and healthy controls through the nCounter technology. We then used a differential expression approach and pathways analysis to detect tissue specific immune severity signals in COVID-19 patients.Mild and asymptomatic cases showed a powerful innate antiviral response in nasal epithelium, characterized by activation of interferon (IFN) pathway and downstream cascades, successfully controlling the infection at local level. In contrast, weak macrophage/monocyte driven innate antiviral response and lack of IFN signalling activity were shown in severe cases. Consequently, oral mucosa from severe patients showed signals of viral activity, cell arresting and viral dissemination to the lower respiratory tract, which ultimately could explain the exacerbated innate immune response and impaired adaptative immune responses observed at systemic level. Results from saliva transcriptome suggest that the buccal cavity might play a key role in SARS-CoV-2 infection and dissemination in patients with worse prognosis.ConclusionsWe found severity-related signatures in patient tissues mainly represented by genes involved in the innate immune system and cytokine/chemokine signalling. Local immune response could be key to determine the course of the systemic response and thus COVID-19 severity. Our findings provide a framework to investigate severity host gene biomarkers and pathways that might be relevant to diagnosis, prognosis, and therapy.
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- 2021
22. A qPCR expression assay of IFI44L gene differentiates viral from bacterial infections in febrile children
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Sara Pischedda, Irene Rivero-Calle, Ruth Barral-Arca, José Gómez-Rial, Alberto Gómez-Carballa, Francisco Barros, Miriam Cebey-López, Federico Martinón-Torres, Jacobo Pardo-Seco, Antonio Salas, and María José Curras-Tuala
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0301 basic medicine ,Male ,Microbiological culture ,Microarray ,Gene Expression ,lcsh:Medicine ,Urine ,Neisseria meningitidis ,Transcriptome ,0302 clinical medicine ,Child ,lcsh:Science ,Multidisciplinary ,gripe humana ,meningitis ,Bacterial Infections ,Clinical routine ,ARN ,Virus Diseases ,Child, Preschool ,Female ,Expression Signature ,Biology ,Real-Time Polymerase Chain Reaction ,Seizures, Febrile ,Article ,orina ,Diagnosis, Differential ,03 medical and health sciences ,expresión génica ,Influenza, Human ,Reference gene ,Humans ,RNA, Messenger ,Transcriptomics ,Gene ,Microarray analysis techniques ,ARN mensajero ,Gene Expression Profiling ,Tumor Suppressor Proteins ,lcsh:R ,Infant ,transcriptoma ,030104 developmental biology ,Infeccións Bacterianas ,Immunology ,infecciones bacterianas ,RNA ,lcsh:Q ,Gene expression ,Bacterial infection ,030217 neurology & neurosurgery ,Biomarkers - Abstract
The diagnosis of bacterial infections in hospital settings is currently performed using bacterial culture from sterile site, but they are lengthy and limited. Transcriptomic biomarkers are becoming promising tools for diagnosis with potential applicability in clinical settings. We evaluated a RT-qPCR assay for a 2-transcript host expression signature (FAM89A and IFI44L genes) inferred from microarray data that allow to differentiate between viral and bacterial infection in febrile children. This assay was able to discriminate viral from bacterial infections (P-value = 1.04 × 10−4; AUC = 92.2%; sensitivity = 90.9%; specificity = 85.7%) and showed very high reproducibility regardless of the reference gene(s) used to normalize the data. Unexpectedly, the monogenic IFI44L expression signature yielded better results than those obtained from the 2-transcript test (P-value = 3.59 × 10−5; AUC = 94.1%; sensitivity = 90.9%; specificity = 92.8%). We validated this IFI44L signature in previously published microarray and whole-transcriptome data from patients affected by different types of viral and bacterial infections, confirming that this gene alone differentiates between both groups, thus saving time, effort, and costs. Herein, we demonstrate that host expression microarray data can be successfully translated into a fast, highly accurate and relatively inexpensive in vitro assay that could be implemented in the clinical routine.
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- 2019
23. Identification of a Minimal 3-Transcript Signature to Differentiate Viral from Bacterial Infection from Best Genome-Wide Host RNA Biomarkers: A Multi-Cohort Analysis
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Ruth Barral-Arca, Antonio Salas, Alberto Gómez-Carballa, Federico Martinón-Torres, Miriam Cebey-López, Xabier Bello, and Jacobo Pardo-Seco
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0301 basic medicine ,transcriptomic biomarkers ,Computational biology ,Biology ,Genome ,Catalysis ,Virus ,Article ,Inorganic Chemistry ,Transcriptome ,lcsh:Chemistry ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Antibiotic resistance ,Meta-Analysis as Topic ,Humans ,multi-cohort ,Physical and Theoretical Chemistry ,Molecular Biology ,Gene ,Pathogen ,lcsh:QH301-705.5 ,microarrays ,Spectroscopy ,RNA signature ,Gene Expression Profiling ,Organic Chemistry ,bacterial infection ,Computational Biology ,General Medicine ,Bacterial Infections ,Antibiotic misuse ,RNAseq ,Computer Science Applications ,030104 developmental biology ,machine learning ,lcsh:Biology (General) ,lcsh:QD1-999 ,ROC Curve ,Virus Diseases ,030220 oncology & carcinogenesis ,Area Under Curve ,Host-Pathogen Interactions ,RNA ,viral infection ,DNA microarray ,transcriptome ,Biomarkers - Abstract
The fight against the spread of antibiotic resistance is one of the most important challenges facing health systems worldwide. Given the limitations of current diagnostic methods, the development of fast and accurate tests for the diagnosis of viral and bacterial infections would improve patient management and treatment, as well as contribute to reducing antibiotic misuse in clinical settings. In this scenario, analysis of host transcriptomics constitutes a promising target to develop new diagnostic tests based on the host-specific response to infections. We carried out a multi-cohort meta-analysis of blood transcriptomic data available in public databases, including 11 different studies and 1209 samples from virus- (n = 695) and bacteria- (n = 514) infected patients. We applied a Parallel Regularized Regression Model Search (PReMS) on a set of previously reported genes that distinguished viral from bacterial infection to find a minimum gene expression bio-signature. This strategy allowed us to detect three genes, namely BAFT, ISG15 and DNMT1, that clearly differentiate groups of infection with high accuracy (training set: area under the curve (AUC) 0.86 (sensitivity: 0.81, specificity: 0.87), testing set: AUC 0.87 (sensitivity: 0.82, specificity: 0.86)). BAFT and ISG15 are involved in processes related to immune response, while DNMT1 is related to the preservation of methylation patterns, and its expression is modulated by pathogen infections. We successfully tested this three-transcript signature in the 11 independent studies, demonstrating its high performance under different scenarios. The main advantage of this three-gene signature is the low number of genes needed to differentiate both groups of patient categories.
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- 2021
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24. Recognising the asymptomatic enemy
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Miriam Cebey-López and Antonio Salas
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2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Comment ,MEDLINE ,Gene Expression ,Biological Evolution ,Virology ,Asymptomatic ,Infectious Diseases ,Humans ,Medicine ,Prospective Studies ,medicine.symptom ,business - Published
- 2020
25. RNA-Seq Data-Mining Allows the Discovery of Two Long Non-Coding RNA Biomarkers of Viral Infection in Humans
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Antonio Salas, Federico Martinón-Torres, María José Curras-Tuala, Sandra Viz-Lasheras, Xabier Bello, Alberto Gómez-Carballa, Ruth Barral-Arca, Sara Pischedda, Miriam Cebey-López, and Universidade de Santiago de Compostela. Departamento de Ciencias Forenses, Anatomía Patolóxica, Xinecoloxía e Obstetricia, e Pediatría
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Adult ,Down-Regulation ,RNA-Seq ,Computational biology ,virus ,Biology ,Monocytes ,Rotavirus Infections ,White People ,Article ,Catalysis ,Inorganic Chemistry ,Transcriptome ,lcsh:Chemistry ,Immune system ,lncRNA ,Asian People ,Downregulation and upregulation ,Machine learning ,Influenza, Human ,Gene expression ,Human Umbilical Vein Endothelial Cells ,Data Mining ,Humans ,Physical and Theoretical Chemistry ,Mexico ,Molecular Biology ,lcsh:QH301-705.5 ,Escherichia coli Infections ,Spectroscopy ,Shotgun sequencing ,Organic Chemistry ,Endothelial Cells ,biomarkers ,General Medicine ,Fibroblasts ,Phenotype ,Long non-coding RNA ,Virus ,Computer Science Applications ,machine learning ,lcsh:Biology (General) ,lcsh:QD1-999 ,Virus Diseases ,Child, Preschool ,Varicella Zoster Virus Infection ,RNA, Long Noncoding ,RNA-seq ,Biomarkers - Abstract
There is a growing interest in unraveling gene expression mechanisms leading to viral host invasion and infection progression. Current findings reveal that long non-coding RNAs (lncRNAs) are implicated in the regulation of the immune system by influencing gene expression through a wide range of mechanisms. By mining whole-transcriptome shotgun sequencing (RNA-seq) data using machine learning approaches, we detected two lncRNAs (ENSG00000254680 and ENSG00000273149) that are downregulated in a wide range of viral infections and different cell types, including blood monocluclear cells, umbilical vein endothelial cells, and dermal fibroblasts. The efficiency of these two lncRNAs was positively validated in different viral phenotypic scenarios. These two lncRNAs showed a strong downregulation in virus-infected patients when compared to healthy control transcriptomes, indicating that these biomarkers are promising targets for infection diagnosis. To the best of our knowledge, this is the very first study using host lncRNAs biomarkers for the diagnosis of human viral infections This study received support from the Instituto de Salud Carlos III: project GePEM (Instituto de Salud Carlos III(ISCIII)/PI16/01478/Cofinanciado FEDER), DIAVIR (Instituto de Salud Carlos III(ISCIII)/DTS19/00049/Cofinanciado FEDER; Proyecto de Desarrollo Tecnológico en Salud) and Resvi-Omics (Instituto de Salud Carlos III(ISCIII)/PI19/01039/Cofinanciado FEDER) and project BI-BACVIR (PRIS-3; Agencia de Conocimiento en Salud (ACIS)—Servicio Gallego de Salud (SERGAS)—Xunta de Galicia; Spain) given to A.S.; and project ReSVinext (Instituto de Salud Carlos III(ISCIII)/PI16/01569/Cofinanciado FEDER), and Enterogen (Instituto de Salud Carlos III(ISCIII)/ PI19/01090/Cofinanciado FEDER) given to F.M.-T SI
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- 2020
26. Impact of rotavirus vaccination on childhood hospitalizations for seizures: Heterologous or unforeseen direct vaccine effects?
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José María Martinón-Martínez, Federico Martinón-Torres, M. J. Curras-Tuala, Irene Rivero-Calle, J. Vilar, José Gómez-Rial, Ruth Barral-Arca, Antonio José Justicia-Grande, Jacobo Pardo-Seco, Antonio Salas, Miriam Cebey-López, and Sara Pischedda
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Male ,Rotavirus ,Vaccination Coverage ,Heterologous ,medicine.disease_cause ,Rotavirus vaccination ,Rotavirus Infections ,Seizures, Febrile ,03 medical and health sciences ,0302 clinical medicine ,030225 pediatrics ,Febrile seizure ,medicine ,Humans ,030212 general & internal medicine ,Retrospective Studies ,General Veterinary ,General Immunology and Microbiology ,business.industry ,Public Health, Environmental and Occupational Health ,Rotavirus Vaccines ,Infant ,medicine.disease ,Virology ,Rotavirus vaccine ,Gastroenteritis ,Vaccination ,Rotavirus infection ,Hospitalization ,Infectious Diseases ,Spain ,Child, Preschool ,Molecular Medicine ,Female ,business - Abstract
There is a growing interest in the possible relationship between rotavirus (RV) vaccine and hospitalizations due to childhood seizures. We explored variation in hospitalization rates after 9 years of vaccination against pre-vaccination period for children5 years of age from Galicia (Northwest Spain) before and after the introduction of the RV vaccines. Hospitalization rates for childhood seizures in Galician children were compared before and after RV vaccine introduction (in 2007) using different statistical approaches, including time series analyses. Our study cohort totaled 7,712 children5 years of age admitted to hospital between 2002 and 2015 for "all kind of childhood seizures". Hospitalization rates decreases steadily with reductions ranging from 22.3% (95% CI: 15.0-29.1) in 2008, to 50.9% (95% CI: 45.5-55.7) in 2014, and significant results were also observed for1, 1, and 2-year-old children in comparison with pre-vaccination period hospitalization rate. Regression models indicate a negative association between RV vaccination and hospitalizations for all kind of seizures. In addition, time series analyses are consistent with this finding and predict that vaccination coverage will affect hospitalization rates for "all kind of seizures" after 9 months. The results strongly support that RV vaccination has significantly reduced hospitalization rates due to childhood seizures.
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- 2018
27. Strong down-regulation of glycophorin genes: A host defense mechanism against rotavirus infection
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Antonio Salas, Juan Carlos Triviño, Irene Rivero-Calle, Federico Martinón-Torres, José Gómez-Rial, Alberto Gómez-Carballa, Guillermo Marco-Puche, Carmen Rodríguez-Tenreiro, Lucía Vilanova-Trillo, and Miriam Cebey-López
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Male ,Rotavirus ,0301 basic medicine ,Microbiology (medical) ,Host Defense Mechanism ,Down-Regulation ,RNA-Seq ,Biology ,medicine.disease_cause ,Microbiology ,Rotavirus Infections ,Virus ,Transcriptome ,03 medical and health sciences ,Interferon ,Genetics ,medicine ,Cluster Analysis ,Humans ,Glycophorin ,Gene Regulatory Networks ,Glycophorins ,Molecular Biology ,Gene ,Ecology, Evolution, Behavior and Systematics ,Disease Resistance ,030102 biochemistry & molecular biology ,Gene Expression Profiling ,High-Throughput Nucleotide Sequencing ,Infant ,Virology ,030104 developmental biology ,Infectious Diseases ,Gene Expression Regulation ,Case-Control Studies ,Child, Preschool ,Multigene Family ,Host-Pathogen Interactions ,biology.protein ,Female ,medicine.drug - Abstract
The mechanisms of rotavirus (RV) infection have been analyzed from different angles but the way in which RV modifies the transcriptome of the host is still unknown. Whole transcriptome shotgun sequencing of peripheral blood samples was used to reveal patterns of expression from the genome of RV-infected patients. RV provokes global changes in the transcriptome of infected cells, involving an over-expression of genes involved in cell cycle and chromatin condensation. While interferon IFI27 was hyper-activated, interferon type II was not suggesting that RV has developed mechanisms to evade the innate response by host cells after virus infection. Most interesting was the inhibition of genes of the glycophorins A and B (GYPA/B) family, which are the major sialoglycoproteins of the human erythrocyte membrane and receptor of several viruses for host invasion. RV infection induces a complex and global response in the host. The strong inhibition of glycophorins suggests a novel defense mechanism of the host to prevent viral infection, inhibiting the expression of receptors used by the virus for infection. The present results add further support to the systemic nature of RV infection.
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- 2016
28. Role of Vitamin D in Hospitalized Children With Lower Tract Acute Respiratory Infections
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Miriam, Cebey-López, Jacobo, Pardo-Seco, Alberto, Gómez-Carballa, Nazareth, Martinón-Torres, Irene, Rivero-Calle, Antonio, Justicia, Lorenzo, Redondo, José María, Martinón-Sánchez, María Del Carmen, Martínez-Padilla, Francisco, Giménez-Sánchez, Antonio, Salas, Federico, Martinón-Torres, and María Cruz León, León
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Male ,Pediatrics ,medicine.medical_specialty ,Intensive Care Units, Pediatric ,Severity of Illness Index ,vitamin D deficiency ,03 medical and health sciences ,Patient Admission ,0302 clinical medicine ,Interquartile range ,030225 pediatrics ,Severity of illness ,Vitamin D and neurology ,medicine ,Humans ,Prospective Studies ,030212 general & internal medicine ,Vitamin D ,Child ,Prospective cohort study ,Respiratory Tract Infections ,Pediatric intensive care unit ,Respiratory tract infections ,business.industry ,Gastroenterology ,Infant ,Length of Stay ,Vitamin D Deficiency ,medicine.disease ,Respiration, Artificial ,Confidence interval ,Spain ,Acute Disease ,Pediatrics, Perinatology and Child Health ,Female ,business ,Child, Hospitalized - Abstract
BACKGROUND Vitamin D is known to have modulatory actions in the immune system. Its influence on the severity of lower tract acute respiratory infections (LT-ARIs) is unclear. OBJECTIVES The aim of the present study was to evaluate the role of vitamin D on LT-ARI in paediatric patients. METHODS Children admitted to hospital with LT-ARI were prospectively recruited through the GENDRES network (March 2009-May 2013). The 25-hydroxyvitamin D (25-OHD) levels were measured by immunoassay. The severity of the illness was evaluated according to clinical scales, length of hospital stay, ventilatory requirements, and pediatric intensive care unit admission. RESULTS A total of 347 patients with a median (interquartile range) age of 8.4 (2.6-21.1) months were included. The mean (SD) 25-OHD levels in our series were 27.1 (11.3) ng/mL. In this study, a cutoff value of ≥30 ng/mL was considered optimal vitamin status. Patients with 25-OHD levels
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- 2016
29. Mortality and morbidity in community-acquired sepsis in European pediatric intensive care units: a prospective cohort study from the European Childhood Life-threatening Infectious Disease Study (EUCLIDS)
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Jan A. Hazelzet, Ria Philipsen, Colin Fink, Jethro Herberg, Navin P. Boeddha, Marieke Emonts, Federico Martinón-Torres, Werner Zenz, Michael Levin, Enitan D. Carrol, Eleanor Pinnock, David Inwald, Luregn J. Schlapbach, Stéphane Paulus, DS Klobassa, Michiel van der Flier, Simon Nadel, Irene Rivero-Calle, Rachel S. Agbeko, Christoph Berger, Fatou Secka, Suzanne T. Anderson, Ronald de Groot, Miriam Cebey-López, Gertjan J. Driessen, AII - Infectious diseases, Amsterdam Neuroscience - Neuroinfection & -inflammation, Neurology, University of Zurich, Hazelzet, Jan A, Posfay Barbe, Klara, Pediatric Surgery, Pediatrics, and Public Health
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Male ,Meningococcal infections ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,Bacteremia ,Critical Care and Intensive Care Medicine ,Community-Acquired Infections/epidemiology ,Cohort Studies ,0302 clinical medicine ,Pediatric/organization & administration ,Prospective Studies ,Sepsis/epidemiology ,030212 general & internal medicine ,Child ,Prospective cohort study ,ddc:618 ,Intensive Care Units, Pediatric/organization & administration ,Sepsis/epidemiology/mortality ,Statistics ,lcsh:Medical emergencies. Critical care. Intensive care. First aid ,11 Medical And Health Sciences ,3. Good health ,Community-Acquired Infections ,Europe ,Intensive Care Units ,Child, Preschool ,Community-Acquired Infections/epidemiology/mortality ,Female ,2706 Critical Care and Intensive Care Medicine ,Pneumococcal infections ,Cohort study ,medicine.medical_specialty ,Adolescent ,RJ ,Pediatric/organization & administration/statistics & numerical data ,610 Medicine & health ,PIM2 ,Intensive Care Units, Pediatric ,Statistics, Nonparametric ,Europe/epidemiology ,Sepsis ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,030225 pediatrics ,Intensive care ,Internal medicine ,medicine ,Humans ,Nonparametric ,Mortality ,Preschool ,Analysis of Variance ,Chi-Square Distribution ,Bacterial disease ,Septic shock ,business.industry ,Research ,Infant ,lcsh:RC86-88.9 ,medicine.disease ,EUCLIDS consortium ,Emergency & Critical Care Medicine ,10036 Medical Clinic ,Morbidity ,business - Abstract
Background: Sepsis is one of the main reasons for non-elective admission to pediatric intensive care units (PICUs), but little is known about determinants influencing outcome. We characterized children admitted with community-acquired sepsis to European PICUs and studied risk factors for mortality and disability.Methods: Data were collected within the collaborative Seventh Framework Programme (FP7)-funded EUCLIDS study, which is a prospective multicenter cohort study aiming to evaluate genetic determinants of susceptibility and/or severity in sepsis. This report includes 795 children admitted with community-acquired sepsis to 52 PICUs from seven European countries between July 2012 and January 2016. The primary outcome measure was in-hospital death. Secondary outcome measures were PICU-free days censured at day 28, hospital length of stay, and disability. Independent predictors were identified by multivariate regression analysis.Results: Patients most commonly presented clinically with sepsis without a source (n = 278, 35%), meningitis/encephalitis (n = 182, 23%), or pneumonia (n = 149, 19%). Of 428 (54%) patients with confirmed bacterial infection, Neisseria meningitidis (n = 131, 31%) and Streptococcus pneumoniae (n = 78, 18%) were the main pathogens. Mortality was 6% (51/795), increasing to 10% in the presence of septic shock (45/466). Of the survivors, 31% were discharged with disability, including 24% of previously healthy children who survived with disability. Mortality and disability were independently associated with S. pneumoniae infections (mortality OR 4.1, 95% CI 1.1–16.0, P = 0.04; disability OR 5.4, 95% CI 1.8–15.8, P P P Conclusions: Despite widespread immunization campaigns, invasive bacterial disease remains responsible for substantial morbidity and mortality in critically ill children in high-income countries. Almost one third of sepsis survivors admitted to the PICU were discharged with some disability. More research is required to delineate the long-term outcome of pediatric sepsis and to identify interventional targets. Our findings emphasize the importance of improved early sepsis-recognition programs to address the high burden of disease.
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- 2018
30. Life-threatening infections in children in Europe (the EUCLIDS Project): a prospective cohort study
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Federico Martinón-Torres, Antonio Salas, Irene Rivero-Calle, Miriam Cebey-López, Jacobo Pardo-Seco, Jethro A Herberg, Navin P Boeddha, Daniela S Klobassa, Fatou Secka, Stephane Paulus, Ronald de Groot, Luregn J Schlapbach, Gertjan J Driessen, Suzanne T Anderson, Marieke Emonts, Werner Zenz, Enitan D Carrol, Michiel Van der Flier, Michael Levin, Lachlan Coin, Stuart Gormley, Shea Hamilton, Jethro Herberg, Bernardo Hourmat, Clive Hoggart, Myrsini Kaforou, Vanessa Sancho-Shimizu, Victoria Wright, Amina Abdulla, Paul Agapow, Maeve Bartlett, Evangelos Bellos, Hariklia Eleftherohorinou, Rachel Galassini, David Inwald, Meg Mashbat, Stefanie Menikou, Sobia Mustafa, Simon Nadel, Rahmeen Rahman, Clare Thakker, Sumit Bokhandi, Sue Power, Heather Barham, Nazima Pathan, Jenna Ridout, Deborah White, Sarah Thurston, Saul Faust, Sanjay Patel, Jenni McCorkell, Patrick Davies, Lindsey Crate, Helen Navarra, Stephanie Carter, Raghu Ramaiah, Rekha Patel, Catherine Tuffrey, Andrew Gribbin, Sharon McCready, Mark Peters, Katie Hardy, Fran Standing, Lauren O'Neill, Eugenia Abelake, Akash Deep, Eniola Nsirim, Andrew Pollard, Louise Willis, Zoe Young, C Royad, Sonia White, Peter Marc Fortune, Phil Hudnott, Antonio Salas Ellacuriaga, Fernando Álvez González, Ruth Barral-Arca, María José Curras-Tuala, Natalia García, Luisa García Vicente, Alberto Gómez-Carballa, Jose Gómez Rial, Andrea Grela Beiroa, Antonio Justicia Grande, Pilar Leboráns Iglesias, Alba Elena Martínez Santos, Nazareth Martinón-Torres, José María Martinón Sánchez, Beatriz Morillo Gutiérrez, Belén Mosquera Pérez, Pablo Obando Pacheco, Sara Pischedda, Carmen Rodríguez-Tenreiro, Lorenzo Redondo-Collazo, Sonia Serén Fernández, María del Sol Porto Silva, Ana Vega, Lucía Vilanova Trillo, Susana Beatriz Reyes, María Cruz León León, Álvaro Navarro Mingorance, Xavier Gabaldó Barrios, Eider Oñate Vergara, Andrés Concha Torre, Ana Vivanco, Reyes Fernández, Francisco Giménez Sánchez, Miguel Sánchez Forte, Pablo Rojo, Jesús Ruiz Contreras, Alba Palacios, Cristina Epalza Ibarrondo, Elizabeth Fernández Cooke, Marisa Navarro, Cristina Álvarez Álvarez, María José Lozano, Eduardo Carreras, Sonia Brió Sanagustín, Olaf Neth, María del Carmen Martínez Padilla, Luis Manuel Prieto Tato, Sara Guillén, Laura Fernández Silveira, David Moreno, A. Marceline van Furth, Michiel van der Flier, Navin Prekash Boeddha, Gertjan JA Driessen, Jan A Hazelzet, Taco W Kuijpers, Dasja Pajkrt, Elisabeth AM Sanders, Diederik van de Beek, Arie van der Ende, Ria LA Philipsen, Abdul OA Adeel, Meike A Breukels, Danielle MC Brinkman, Carla CMM de Korte, Esther de Vries, Wouter J de Waal, Roel Dekkers, Anouk Dings-Lammertink, Rienus A Doedens, Albertine E Donker, Mieke Dousma, Tina E Faber, G Peter JM Gerrits, Jan AM Gerver, Jojanneke Heidema, Jenneke Homan-van der Veen, Monique AM Jacobs, Nicolaas JG Jansen, Pawel Kawczynski, Kristine Klucovska, Martin CJ Kneyber, Yvonne Koopman-Keemink, Veerle J Langenhorst, José Leusink, Bettina F Loza, Istvan T Merth, Carien J Miedema, Chris Neeleman, Jeroen G Noordzij, Charles C Obihara, A Lidy T van Overbeek - van Gils, Geriska H Poortman, Steph T Potgieter, Joke Potjewijd, Philippe PR Rosias, Tom Sprong, Gavin W ten Tussher, Boony J Thio, Gerdien A Tramper-Stranders, Marcel van Deuren, Henny van der Meer, Andre JM van Kuppevelt, Anne-Marie van Wermeskerken, Wim A Verwijs, Tom FW Wolfs, Luregn Jan Schlapbach, Philipp Agyeman, Christoph Aebi, Christoph Berger, Eric Giannoni, Martin Stocker, Klara M Posfay-Barbe, Ulrich Heininger, Sara Bernhard-Stirnemann, Anita Niederer-Loher, Christian Kahlert, Paul Hasters, Christa Relly, Walter Baer, Enitan Carrol, Stéphane Paulus, Hannah Frederick, Rebecca Jennings, Joanne Johnston, Rhian Kenwright, Colin G Fink, Elli Pinnock, Rachel Sarah Agbeko, Kalifa A Bojang, Isatou Sarr, Ngange Kebbeh, Gibbi Sey, Momodou Saidykhan, Fatoumata Cole, Gilleh Thomas, Martin Antonio, Daniela Sabine Klobassa, Alexander Binder, Nina Alexandra Schweintzger, Manfred Sagmeister, Hinrich Baumgart, Markus Baumgartner, Uta Behrends, Ariane Biebl, Robert Birnbacher, Jan-Gerd Blanke, Carsten Boelke, Kai Breuling, Jürgen Brunner, Maria Buller, Peter Dahlem, Beate Dietrich, Ernst Eber, Johannes Elias, Josef Emhofer, Rosa Etschmaier, Sebastian Farr, Ylenia Girtler, Irina Grigorow, Konrad Heimann, Ulrike Ihm, Zdenek Jaros, Hermann Kalhoff, Wilhelm Kaulfersch, Christoph Kemen, Nina Klocker, Bernhard Köster, Benno Kohlmaier, Eleni Komini, Lydia Kramer, Antje Neubert, Daniel Ortner, Lydia Pescollderungg, Klaus Pfurtscheller, Karl Reiter, Goran Ristic, Siegfried Rödl, Andrea Sellner, Astrid Sonnleitner, Matthias Sperl, Wolfgang Stelzl, Holger Till, Andreas Trobisch, Anne Vierzig, Ulrich Vogel, Christina Weingarten, Stefanie Welke, Andreas Wimmer, Uwe Wintergerst, Daniel Wüller, Andrew Zaunschirm, Ieva Ziuraite, Veslava Žukovskaja, Posfay Barbe, Klara, Pediatrics, Huisarts & Ziekenhuis, Tranzo, Scientific center for care and wellbeing, ARD - Amsterdam Reproduction and Development, AII - Infectious diseases, Paediatric Infectious Diseases / Rheumatology / Immunology, ANS - Neuroinfection & -inflammation, Neurology, Medical Microbiology and Infection Prevention, Pediatric surgery, Amsterdam Reproduction & Development (AR&D), The European Society for Paediatric Infectious Diseases, Meningitis Research Foundation, Imperial College Healthcare NHS Trust- BRC Funding, Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), University of Zurich, and Martinón-Torres, Federico
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Male ,Pediatrics ,RJ101 ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,Severity of Illness Index ,Cohort Studies ,0302 clinical medicine ,Cost of Illness ,Developmental and Educational Psychology ,030212 general & internal medicine ,Prospective Studies ,Sepsis/epidemiology ,Prospective cohort study ,Child ,media_common ,ddc:618 ,Bacterial Infections ,Europe ,Child, Preschool ,Cohort ,Female ,Algorithms ,Cohort study ,medicine.medical_specialty ,610 Medicine & health ,Europe/epidemiology ,Sepsis ,03 medical and health sciences ,All institutes and research themes of the Radboud University Medical Center ,030225 pediatrics ,Severity of illness ,medicine ,media_common.cataloged_instance ,Humans ,2735 Pediatrics, Perinatology and Child Health ,European union ,Preschool ,Disease burden ,3204 Developmental and Educational Psychology ,business.industry ,Infant, Newborn ,Infant ,medicine.disease ,Newborn ,Pneumonia ,10036 Medical Clinic ,Pediatrics, Perinatology and Child Health ,business ,Bacterial Infections/epidemiology - Abstract
Background Sepsis and severe focal infections represent a substantial disease burden in children admitted to hospital. We aimed to understand the burden of disease and outcomes in children with life-threatening bacterial infections in Europe. Methods The European Union Childhood Life-threatening Infectious Disease Study (EUCLIDS) was a prospective, multicentre, cohort study done in six countries in Europe. Patients aged 1 month to 18 years with sepsis (or suspected sepsis) or severe focal infections, admitted to 98 participating hospitals in the UK, Austria, Germany, Lithuania, Spain, and the Netherlands were prospectively recruited between July 1, 2012, and Dec 31, 2015. To assess disease burden and outcomes, we collected demographic and clinical data using a secured web-based platform and obtained microbiological data using locally available clinical diagnostic procedures. Findings 2844 patients were recruited and included in the analysis. 1512 (53·2%) of 2841 patients were male and median age was 39·1 months (IQR 12·4–93·9). 1229 (43·2%) patients had sepsis and 1615 (56·8%) had severe focal infections. Patients diagnosed with sepsis had a median age of 27·6 months (IQR 9·0–80·2), whereas those diagnosed with severe focal infections had a median age of 46·5 months (15·8–100·4; pInterpretation Mortality in children admitted to hospital for sepsis or severe focal infections is low in Europe. The disease burden is mainly in children younger than 5 years and is largely due to vaccine-preventable meningococcal and pneumococcal infections. Despite the availability and application of clinical procedures for microbiological diagnosis, the causative organism remained unidentified in approximately 50% of patients.
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- 2018
31. Impact of Rotavirus Vaccination on Childhood Hospitalization for Seizures
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José Gómez-Rial, Antonio Salas, José María Martinón-Sánchez, Federico Martinón-Torres, Jacobo Pardo-Seco, Carmen Rodríguez-Tenreiro, Nazareth Martinón-Torres, and Miriam Cebey-López
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Male ,Microbiology (medical) ,Pediatrics ,medicine.medical_specialty ,medicine.disease_cause ,Rotavirus vaccination ,Seizures ,Rotavirus ,medicine ,Humans ,Retrospective Studies ,business.industry ,Incidence ,Incidence (epidemiology) ,Vaccination ,Infant, Newborn ,Rotavirus Vaccines ,Infant ,Acute gastroenteritis ,Rotavirus vaccine ,Confidence interval ,Hospitalization ,Infectious Diseases ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Cohort ,Female ,business - Abstract
Background: Rotavirus vaccine (RV) might reduce the risk of hospitalization due to childhood seizures (CS). We aimed to identify and assess variations in the incidence of hospitalizations for CS among children
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- 2015
32. Whole Exome Sequencing reveals new candidate genes in host genomic susceptibility to Respiratory Syncytial Virus Disease
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Jacobo Pardo-Seco, Laura Moreno-Galarraga, Rosaura Leis, Lorenzo Redondo Collazo, Sara Pischedda, Ignacio Oulego-Erroz, Jorge Amigo, MARIA LUZ GARCIA-GARCIA, Pablo Obando-Pacheco, Cristina Calvo, Federico Martinon-Torres, Irene Rivero Calle, Ruth Barral Arca, Jose Gómez Rial, Beatriz Morillo Gutierrez, Alberto Gómez-Carballa, María José Currás Tuala, Antonio Salas, Máximo Fraga Rodríguez, and Miriam Cebey-López
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0301 basic medicine ,Candidate gene ,lcsh:Medicine ,Respiratory Syncytial Virus Infections ,Biology ,Genome ,Polymorphism, Single Nucleotide ,Virus ,Article ,Whole Exome Sequencing ,03 medical and health sciences ,0302 clinical medicine ,Exome Sequencing ,medicine ,Humans ,Genetic Predisposition to Disease ,1000 Genomes Project ,lcsh:Science ,Gene ,Exome ,Exome sequencing ,Genetic Association Studies ,Genetics ,Multidisciplinary ,Genome, Human ,lcsh:R ,Infant, Newborn ,Infant ,medicine.disease ,Virology ,030104 developmental biology ,Gene Ontology ,Bronchiolitis ,Case-Control Studies ,Respiratory Syncytial Virus, Human ,Host-Pathogen Interactions ,lcsh:Q ,030217 neurology & neurosurgery - Abstract
Respiratory syncytial virus (RSV) is an important cause of serious lower respiratory tract disease in infants. Several studies have shown evidence pointing to the genome of the host as an important factor determining susceptibility to respiratory disease caused by RSV. We sequenced the complete exomes of 54 patients infected by RSV that needed hospitalization due to development of severe bronchiolitis. The Iberian sample (IBS) from The 1000 Genomes Project (1000G) was used as control group; all the association results were pseudo-replicated using other 1000G-European controls and Spanish controls. The study points to SNP rs199665292 in the olfactory receptor (OR) gene OR13C5 as the best candidate variant (P-value = 1.16 × 10−12; OR = 5.56). Genetic variants at HLA genes (HLA-DQA1, HLA-DPB1), and in the mucin 4 gene (MUC4) also emerge as susceptibility candidates. By collapsing rare variants in genes and weighing by pathogenicity, we obtained confirmatory signals of association in the OR gene OR8U1/OR8U8, the taste receptor TAS2R19, and another mucin gene (MUC6). Overall, we identified new predisposition variants and genes related to RSV infection. Of special interest is the association of RSV to olfactory and taste receptors; this finding is in line with recent evidence pointing to their role in viral infectious diseases.
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- 2017
33. Lifestyle and comorbid conditions as risk factors for community-acquired pneumonia in outpatient adults (NEUMO-ES-RISK project)
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Federico Martinón-Torres, Jose Yuste, Irene Rivero-Calle, I Jimeno, Manuel Linares-Rufo, J L Díaz-Maroto, E. Mascarós, Miriam Cebey-López, Jacobo Pardo-Seco, Ángel Gil, Diego A Vargas, D. Ocaña, Esther Redondo, and J Molina
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Adult ,Male ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,community-acquired pneumonia ,Respiratory Infection ,HIV Infections ,Comorbidity ,Primary care ,Pulmonary Disease, Chronic Obstructive ,primary care ,03 medical and health sciences ,0302 clinical medicine ,Community-acquired pneumonia ,Risk Factors ,Internal medicine ,Outpatients ,Prevalence ,medicine ,Humans ,030212 general & internal medicine ,Life Style ,Aged ,Retrospective Studies ,Asthma ,COPD ,business.industry ,Incidence ,Incidence (epidemiology) ,Smoking ,Age Factors ,Pneumonia ,Dental hygiene ,Middle Aged ,Oral Hygiene ,medicine.disease ,Community-Acquired Infections ,vaccine-preventable diseases ,030228 respiratory system ,Spain ,Female ,Vaccine-preventable diseases ,business - Abstract
IntroductionInformation about community-acquired pneumonia (CAP) risk in primary care is limited. We assess different lifestyle and comorbid conditions as risk factors (RF) for CAP in adults in primary care.MethodsA retrospective-observational-controlled study was designed. Adult CAP cases diagnosed at primary care in Spain between 2009 and 2013 were retrieved using the National Surveillance System of Primary Care Data (BiFAP). Age-matched and sex-matched controls were selected by incidence density sampling (ratio 2:1). Associations are presented as percentages and OR. Binomial regression models were constructed to avoid bias effects.Results51 139 patients and 102 372 controls were compared. Mean age (SD) was 61.4 (19.9) years. RF more significantly linked to CAP were: HIV (OR [95% CI]: 5.21 [4.35 to 6.27]), chronic obstructive pulmonary disease (COPD) (2.97 [2.84 to 3.12]), asthma (2.16 [2.07,2.26]), smoking (1.96 [1.91 to 2.02]) and poor dental hygiene (1.45 [1.41 to 1.49]). Average prevalence of any RF was 82.2% in cases and 69.2% in controls (2.05 [2.00 to 2.10]). CAP rate increased with the accumulation of RF and age: risk associated with 1RF was 1.42 (1.37 to 1.47) in 18–60-year-old individuals vs 1.57 (1.49 to 1.66) in >60 years of age, with 2RF 1.88 (1.80 to 1.97) vs 2.35 (2.23, 2.48) and with ≥ 3 RF 3.11 (2.95, 3.30) vs 4.34 (4.13 to 4.57).DiscussionPrevalence of RF in adult CAP in primary care is high. Main RFs associated are HIV, COPD, asthma, smoking and poor dental hygiene. Our risk stacking results could help clinicians identify patients at higher risk of pneumonia.
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- 2019
34. Diagnostic test accuracy of a 2-transcript host RNA signature for discriminating bacterial vs viral infection in febrile children
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Federico Martinón-Torres, Hannah Shailes, Sanjay Patel, Victoria J. Wright, Clive J. Hoggart, Antonio Salas, Andrew J. Pollard, Adriana H. Tremoulet, Lachlan J. M. Coin, Saul N. Faust, Stuart Gormley, Michael J. Carter, Jane C. Burns, John T. Kanegaye, Chisato Shimizu, Taco W. Kuijpers, Hariklia Eleftherohorinou, Myrsini Kaforou, Michael Levin, Jethro Herberg, Miriam Cebey-López, Victoria A. Janes, Anouk M. Barendregt, Apollo - University of Cambridge Repository, Imperial College Healthcare NHS Trust- BRC Funding, Graduate School, Paediatric Infectious Diseases / Rheumatology / Immunology, AII - Amsterdam institute for Infection and Immunity, and Landsteiner Laboratory
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0301 basic medicine ,Male ,Antibiotics ,Severity of Illness Index ,Medical and Health Sciences ,0302 clinical medicine ,IRIS Consortium ,Diagnosis ,2.2 Factors relating to the physical environment ,Prospective Studies ,Aetiology ,Prospective cohort study ,Child ,screening and diagnosis ,Coinfection ,General Medicine ,11 Medical And Health Sciences ,Bacterial Infections ,3. Good health ,Anti-Bacterial Agents ,Detection ,Infectious Diseases ,Virus Diseases ,Child, Preschool ,Area Under Curve ,Female ,Indeterminate ,Infection ,4.2 Evaluation of markers and technologies ,Genetic Markers ,Risk ,Fever ,medicine.drug_class ,Meningococcal disease ,Sensitivity and Specificity ,Diagnosis, Differential ,Vaccine Related ,03 medical and health sciences ,Clinical Research ,030225 pediatrics ,Intensive care ,General & Internal Medicine ,Severity of illness ,medicine ,Genetics ,Humans ,Antigens ,Preschool ,business.industry ,Gene Expression Profiling ,Infant ,medicine.disease ,4.1 Discovery and preclinical testing of markers and technologies ,Cytoskeletal Proteins ,030104 developmental biology ,Logistic Models ,Emerging Infectious Diseases ,Good Health and Well Being ,Genetic marker ,Immunology ,Differential ,RNA ,business ,Biomarkers - Abstract
Importance Because clinical features do not reliably distinguish bacterial from viral infection, many children worldwide receive unnecessary antibiotic treatment, while bacterial infection is missed in others. Objective To identify a blood RNA expression signature that distinguishes bacterial from viral infection in febrile children. Design, Setting, and Participants Febrile children presenting to participating hospitals in the United Kingdom, Spain, the Netherlands, and the United States between 2009-2013 were prospectively recruited, comprising a discovery group and validation group. Each group was classified after microbiological investigation as having definite bacterial infection, definite viral infection, or indeterminate infection. RNA expression signatures distinguishing definite bacterial from viral infection were identified in the discovery group and diagnostic performance assessed in the validation group. Additional validation was undertaken in separate studies of children with meningococcal disease (n = 24) and inflammatory diseases (n = 48) and on published gene expression datasets. Exposures A 2-transcript RNA expression signature distinguishing bacterial infection from viral infection was evaluated against clinical and microbiological diagnosis. Main Outcomes and Measures Definite bacterial and viral infection was confirmed by culture or molecular detection of the pathogens. Performance of the RNA signature was evaluated in the definite bacterial and viral group and in the indeterminate infection group. Results The discovery group of 240 children (median age, 19 months; 62% male) included 52 with definite bacterial infection, of whom 36 (69%) required intensive care, and 92 with definite viral infection, of whom 32 (35%) required intensive care. Ninety-six children had indeterminate infection. Analysis of RNA expression data identified a 38-transcript signature distinguishing bacterial from viral infection. A smaller (2-transcript) signature (FAM89A and IFI44L) was identified by removing highly correlated transcripts. When this 2-transcript signature was implemented as a disease risk score in the validation group (130 children, with 23 definite bacterial, 28 definite viral, and 79 indeterminate infections; median age, 17 months; 57% male), all 23 patients with microbiologically confirmed definite bacterial infection were classified as bacterial (sensitivity, 100% [95% CI, 85%-100%]) and 27 of 28 patients with definite viral infection were classified as viral (specificity, 96.4% [95% CI, 89.3%-100%]). When applied to additional validation datasets from patients with meningococcal and inflammatory diseases, bacterial infection was identified with a sensitivity of 91.7% (95% CI, 79.2%-100%) and 90.0% (95% CI, 70.0%-100%), respectively, and with specificity of 96.0% (95% CI, 88.0%-100%) and 95.8% (95% CI, 89.6%-100%). Of the children in the indeterminate groups, 46.3% (63/136) were classified as having bacterial infection, although 94.9% (129/136) received antibiotic treatment. Conclusions and Relevance This study provides preliminary data regarding test accuracy of a 2-transcript host RNA signature discriminating bacterial from viral infection in febrile children. Further studies are needed in diverse groups of patients to assess accuracy and clinical utility of this test in different clinical settings.
- Published
- 2016
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