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116 results on '"Cebey-López, Miriam"'

1. Host gene expression signatures to identify infection type and organ dysfunction in children evaluated for sepsis: a multicentre cohort study

Author

Levin, Michael, Coin, Lachlan, Gormley, Stuart, Hamilton, Shea, Hoggart, Clive, Kaforou, Myrsini, Sancho-Shimizu, Vanessa, Wright, Victoria, Abdulla, Amina, Agapow, Paul, Bartlett, Maeve, Eleftherohorinou, Hariklia, Galassini, Rachel, Inwald, David, Mashbat, Meg, Menikou, Stephanie, Mustafa, Sobia, Nadel, Simon, Rahman, Rahmeen, Shailes, Hannah, Thakker, Clare, Bokhandi, S., Power, Sue, Barham, Heather, Pathan, N., Ridout, Jenna, White, Deborah, Thurston, Sarah, Faust, S., Patel, S., McCorkell, Jenni, Davies, P., Crate, Lindsey, Navarra, Helen, Carter, Stephanie, Ramaiah, R., Patel, Rekha, Tuffrey, Catherine, Gribbin, Andrew, McCready, Sharon, Peters, Mark, Hardy, Katie, Standing, Fran, O'Neill, Lauren, Abelake, Eugenia, Deep, Akash, Nsirim, Eniola, Pollard, Andrew, Willis, Louise, Young, Zoe, Royad, C., White, Sonia, Fortune, Peter-Marc, Hudnott, Phil, Martinón-Torres, Federico, Salas, Antonio, Álvez González, Fernando, Barral-Arca, Ruth, Cebey-López, Miriam, Curras-Tuala, María José, García, Natalia, García Vicente, Luisa, Gómez-Carballa, Alberto, Gómez Rial, Jose, Grela Beiroa, Andrea, Justicia Grande, Antonio, Leboráns Iglesias, Pilar, Martínez Santos, Alba Elena, Martinón-Torres, Nazareth, Martinón Sánchez, José María, Morillo Gutiérrez, Beatriz, Mosquera Pérez, Belén, Obando Pacheco, Pablo, Pardo-Seco, Jacobo, Pischedda, Sara, Rivero-Calle, Irene, Rodríguez-Tenreiro, Carmen, Redondo-Collazo, Lorenzo, Salas Ellacuriaga, Antonio, Fernández, Sonia Serén, del Sol Porto Silva, María, Vega, Ana, Vilanova Trillo, Lucía, Reyes, Susana Beatriz, Cruz León León, María, Navarro Mingorance, Álvaro, Gabaldó Barrio, Xavier, Oñate Vergara, Eider, Concha Torre, Andrés, Vivanco, Ana, Fernández, Reyes, Giménez Sánchez, Francisco, Sánchez Forte, Miguel, Rojo, Pablo, Contreras, J. Ruiz, Palacios, Alba, Epalza Ibarrondo, Cristina, Fernández Cooke, Elizabeth, Navarro, Marisa, Álvarez Álvarez, Cristina, José Lozano, María, Carreras, Eduardo, Brió Sanagustín, Sonia, Neth, Olaf, Martínez Padilla, Mª del Carmen, Prieto Tato, Luis Manuel, Guillén, Sara, Fernández Silveira, Laura, Moreno, David, de Groot, R., Tutu van Furth, A.M., van der Flier, M., Boeddha, N.P., Driessen, G.J.A., Emonts, M., Hazelzet, J.A., Kuijpers, T.W., Pajkrt, D., Sanders, E.A.M., van de Beek, D., van der Ende, A., Philipsen, H.L.A., Adeel, A.O.A., Breukels, M.A., Brinkman, D.M.C., de Korte, C.C.M.M., de Vries, E., de Waal, W.J., Dekkers, R., Dings-Lammertink, A., Doedens, R.A., Donker, A.E., Dousma, M., Faber, T.E., Gerrits, G.P.J.M., Gerver, J.A.M., Heidema, J., Homan-van der Veen, J., Jacobs, M.A.M., Jansen, N.J.G., Kawczynski, P., Klucovska, K., Kneyber, M.C.J., Koopman-Keemink, Y., Langenhorst, V.J., Leusink, J., Loza, B.F., Merth, I.T., Miedema, C.J., Neeleman, C., Noordzij, J.G., Obihara, C.C., van Overbeek- van Gils, A.L.T., Poortman, G.H., Potgieter, S.T., Potjewijd, J., Rosias, P.P.R., Sprong, T., ten Tussher, G.W., Thio, B.J., Tramper-Stranders, G.A., van Deuren, M., van der Meer, H., van Kuppevelt, A.J.M., van Wermeskerken, A.M., Verwijs, W.A., Wolfs, T.F.W., Schlapbach, Luregn J., Agyeman, Philipp, Aebi, Christoph, Giannoni, Eric, Stocker, Martin, Posfay-Barbe, Klara M., Heininger, Ulrich, Bernhard-Stirnemann, Sara, Niederer-Loher, Anita, Kahlert, Christian, Hasters, Paul, Relly, Christa, Baer, Walter, Berger, Christoph, Carrol, Enitan D., Paulus, Stéphane, Frederick, Hannah, Jennings, Rebecca, Johnston, Joanne, Kenwright, Rhian, Fink, Colin G, Pinnock, Elli, Emonts, Marieke, Agbeko, Rachel, Anderson, Suzanne, Secka, Fatou, Bojang, Kalifa, Sarr, Isatou, Kebbeh, Ngange, Sey, Gibbi, Saidykhan, Momodou, Cole, Fatoumata, Thomas, Gilleh, Antonio, Martin, Zenz, Werner, Kohlfürst, Daniela S., Binder, Alexander, Schweintzger, Nina A., Sagmeister, Manfred, Baumgart, Hinrich, Baumgartner, Markus, Behrends, Uta, Biebl, Ariane, Birnbacher, Robert, Blanke, Jan-Gerd, Boelke, Carsten, Breuling, Kai, Brunner, Jürgen, Buller, Maria, Dahlem, Peter, Dietrich, Beate, Eber, Ernst, Elias, Johannes, Emhofer, Josef, Etschmaier, Rosa, Farr, Sebastian, Girtler, Ylenia, Grigorow, Irina, Heimann, Konrad, Ihm, Ulrike, Jaros, Zdenek, Kalhoff, Hermann, Kaulfersch, Wilhelm, Kemen, Christoph, Klocker, Nina, Köster, Bernhard, Kohlmaier, Benno, Komini, Eleni, Kramer, Lydia, Neubert, Antje, Ortner, Daniel, Pescollderungg, Lydia, Pfurtscheller, Klaus, Reiter, Karl, Ristic, Goran, Rödl, Siegfried, Sellner, Andrea, Sonnleitner, Astrid, Sperl, Matthias, Stelzl, Wolfgang, Till, Holger, Trobisch, Andreas, Vierzig, Anne, Vogel, Ulrich, Weingarten, Christina, Welke, Stefanie, Wimmer, Andreas, Wintergerst, Uwe, Wüller, Daniel, Zaunschirm, Andrew, Ziuraite, Ieva, Žukovskaja, Veslava, Hibberd, Martin L., Davila, Sonia, Delany, Isabel, Schlapbach, Luregn J, Raman, Sainath, Sharp, Nathalie, Phillips, Natalie, Irwin, Adam, Balch, Ross, Harley, Amanda, Johnson, Kerry, Sever, Zoe, George, Shane, Grimwood, Keith, Snelling, Peter J, Chavan, Arjun, Kitcatt, Eleanor, Lawton, Luke, Hempenstall, Allison, Pilot, Pelista, Gibbons, Kristen S, Le Marsney, Renate, Blumenthal, Antje, Ganesamoorthy, Devika, Pardo, Carolyn, Kling, Jessica, McPherson, Stephen, MacDonald, Anna D, Bialasiewicz, Seweryn, Pham, Trang, Wilson, Clare, Sharp, Natalie, Kling, Jessica C, McPherson, Stephen J, Herberg, Jethro A, and Coin, Lachlan J M

Published
2024
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2. A multi-platform approach to identify a blood-based host protein signature for distinguishing between bacterial and viral infections in febrile children (PERFORM): a multi-cohort machine learning study

Author

Jackson, Heather Ruth, Zandstra, Judith, Menikou, Stephanie, Hamilton, Shea, McArdle, Andrew J, De, Tisham, Agyeman, Philipp K A, Von Both, Ulrich, Carrol, Enitan D, Emonts, Marieke, Eleftheriou, Irini, Van der Flier, Michiel, Fink, Colin, De Groot, Ronald, Moll, Henriette A, Pokorn, Marko, Pollard, Andrew, Schlapbach, Luregn J, Tsolia, Maria, Usuf, Effua, Wright, Victoria, Yeung, Shunmay, Zavadska, Dace, Zenz, Werner, Coin, Lachlan JM, Cunnington, Aubrey J, Martinon-Torres, Federico, Herberg, Jethro, De Jonge, Marien I, Levin, Michael, Kuijpers, Taco, Kaforou, Myrsini, Abdulla, Amina, Aebi, Christoph, Agbeko, Rachel, Ali, Ladan, Alkema, Wynand, Allen, Karen, Anderson, Suzanne, Ansari, Imran, Arif, Tasnim, Avramoska, Tanja, Baas, Bryan, Bahovec, Natalija, Balode, Anda, Bãrdzdina, Arta, Barendregt, A M, Barral-Arca, Ruth, Bath, David, Bauchinger, Sebastian, Baumard, Lucas, Baumgart, Hinrich, Baxter, Frances, Bell, Kathryn, Bell, Ashley, Bello, Xabier, Bellos, Evangelos, Benesch, Martin, Bennet, Joshua, Berger, Christoph, Bernhard-Stirnemann, Sara, Bibi, Sagida, Bidlingmaier, Christoph, Binder, Alexander, Binder, Vera, Blackmore, Jennifer, Bojang, Kalifa, Borensztajn, Dorine M, Brengel-Pesce, Karen, Broderick, Claire, Buschbeck, Judith, Calvo-Bado, Leonides, Carnota, Sandra, Carter, Michael J, Castro, María Barreiro, Cebey-López, Miriam, Ceesay, Samba, Ceolotto, Astrid, Chan, Adora, Cocklin, Elizabeth, Collings, Kalvin, Crulley, Stephen, Curras-Tuala, María José, D'alessandro, Umberto, D'Souza, Giselle, Danhauser, Katharina, Darboe, Saffiatou, Darnell, Sarah, De Haan, L, De Vries, Gabriella, Deksne, Dãrta, Devine, Kirsty, Dewez, Juan Emmanuel, Dik, W, Dudley, Julia, Eber, Ernst, Fabian, Daniel, Farto, Cristina Balo, Fernández, Sonia Serén, Fidler, Katy, Fitchett, Elizabeth, Galassini, Rachel, Gallisti, Siegfried, García, Mirian Ben, Gardovska, Dace, Geissler, J, Gerrits, G P J M, Giannoni, Eric, Gloerich, Jolein, Gómez-Carballa, Alberto, González, Fernando Álves, Gores, Gunther, Grãvele, Dagne, Griese, Matthias, Grope, Ilze, Gurung, Meeru, Haas, Nikolaus, Habgood-Coote, Dominic, Hagedoorn, Nienke N, Haidl, Harald, Harrison, Rebekah, Hauer, Almuthe, Heidema, J, Heininger, Ulrich, Henriet, Stefanie, Hibberd, Martin, Hoggart, Cllive, Hösele, Susanne, Hourmat, Sara, Hude, Christa, Huijnen, Martijn, Iglesias, Pilar Leboráns, Iglesias, Marisol Vilas, Jennings, Rebecca, Johnson, Joanne, Jongerius, Ilse, Jorgensen, Rikke, Kahlert, Christian, Kandasamy, Rama, Kappler, Matthias, Keldorfer, Markus, Kelly, Dominic F, Khanijau, Aakash, Kim, Nayoung, Kim, Eunjung, King, Sharon, Kolberg, Laura, Kolnik, Mojca, Kloosterhuis, Lieke, Kohlfürst, Daniela S, Kohlmaier, Benno, Krenn, Larissa, Leigh, Simon, Leitner, Manuel, Leurent, Baptiste, Lim, Emma, Lin, Naomi, Liu, Ching-Chuan, Löffler, Sabine, Lurz, Eberhard, Mackerness, Christine, Maconochie, Ian, Mallet, Francois, Marmarinos, Antonis, Martin, Alex, Martin, Mike, Martinón Sánchez, José María, Martinón-Torres, Nazareth, McAlinden, Paul, McDonald, Sam, McDonell, Anne, Meiere, Anija, Meierford, Anne, Miedema, C J, Miners, Alec, Mistry, Ravi, Mommert, Marine, Morris, Sophie, Muench, Georg, Murdoch, David R, Mustafa, Sobia, Natalucci, Giancarlo, Neeleman, C, Newall, Karen, Nichols, Samuel, Niederer-Loher, Anita, Niedrist, Tobias, Nijman, Ruud, Nokalna, Ieve, Nordberg, Gudrun, O'Connor, Daniel, Obihara, C C, Oliver, Zoe, Oosthoek, Wilma, Ora, Miguel Sadiki, Osterman, Veronika, Pachot, Alexandre, Pajkrt, D, Pardo-Seco, Jacobo, Pavãre, Jana, Paz, Ivonne Pena, Paulus, Stéphane, Pérez, Belén Mosquera, Persand, Salina, Pfleger, Andreas, Pfurtscheller, Klaus, Philipsen, Ria, Pickering, Alisa, Pierce, Benjamin, Pilch, Heidemarie, Pischedda, Sara, Pölz, Lena, Posfay-Barbe, Klara M, Powell, Oliver, Prunk, Petra, Pučuka, Zanda, Rajic, Glorija, Rashid, Aqeela, Redondo-Collazo, Lorenzo, Reiter, Karl, Relly, Christa, Rhodes, Mathew, Rial, Jose Gómez, Richmond, Vivien, Riedel, Thomas, Rivero Calle, Irene, Roca, Anna, Rödl, Siegfried, Rodríguez, Lidia Piñeiro, Rodríguez-Tenreiro, Carmen, Romaine, Sam, Rowlands, Emily, Rudzate, Aleksandra, Sagmeister, Manfred, Saidykhan, Momodou, Sallas, Antonio, Sarr, Isatou, Schoen, Carola, Schonenberg, D, Schweintzger, Nina, Secka, Fatou, Selecka, Katrīna, Shah, Priyen, Shen, Ching-Fen, Shrestha, Shrijana, Skrabl-Baumgartner, Andrea, Soon, Joshua, Sperl, Matthias, Sprenkeler, Evelien, Spyridis, Nikos, Srovin, Tina Plankar, Stampfer, Laura, Stevens, Molly, Stocker, Martin, Strenger, Volker, Suárez, Carlos Durán, Svile, Dace, Syggelou, Kelly, Tal, Chantal, Tambouratzi, Maria, Tavliavini, Emma, Thakker, Clare, Thomson, Evelyn, Throson, Stephen, Till, Holger, Tramper-Stranders, G A, Trasorras, Cristina Serén, Trobisch, Andreas, Urbãne, Urzula Nora, Usman, Mariama, Valentine, Lucille, Van Aerde, Koen, Van den Berg, J M, Van den Broek, Bryan, Van der Giessen, Ilona, Van der Kuip, M, Van der Velden, Fabian, Van Furth, A M, Van Gool, Alain J, Van Leur, M, van Mierlo, G, Vázquez, Sara Ray, Vermont, Clementien, Vicente, Luisa García, Vincek, Katarina, Vito, Ortensia, Voice, Marie, Wallia, Diane, Walsh, Ben, Wang, Shih-Min, Wedderburn, Catherine, Willems, Esther, Wilson, Clare, Wood, Amanda, Woodsford, Phil, Wyss, Verena, Xagorari, Marietta, Zachariasse, Joany, Zaman, Syed M A, Zurl, Christoph, Zwerenz, Manuela, Jackson, Heather R, Hamilton, Melissa Shea, Fischer, Roman, Thorne, Adam M, Huang, Honglei, Tanck, Michael W, Jansen, Machiel H, Pollard, Andrew J, Tsolia, Maria N, Wright, Victoria J, Coin, Lachlan J M, Casals-Pascual, Climent, Herberg, Jethro A, de Jonge, Marien I, and Kuijpers, Taco W

Published
2023
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3. Relationship between molecular pathogen detection and clinical disease in febrile children across Europe: a multicentre, prospective observational study

Author

Shah, Priyen, Voice, Marie, Calvo-Bado, Leonides, Calle, Irene Rivero, Morris, Sophie, Nijman, Ruud, Broderick, Claire, De, Tisham, Eleftheriou, Irini, Galassini, Rachel, Khanijau, Aakash, Kolberg, Laura, Kolnik, Mojca, Rudzate, Aleksandra, Sagmeister, Manfred, Schweintzger, Nina, Secka, Fatou, Thakker, Clare, Van der Velden, Fabian, Vermont, Clementien, Vincek, Katarina, Agyeman, Philipp K.A., Cunnington, Aubrey J., De Groot, Ronald, Emonts, Marieke, Fidler, Katy, Kuijpers, Taco, Mommert-Tripon, Marine, Brengel-Pesce, Karen, Mallet, Francois, Moll, Henriette, Paulus, Stéphane, Pokorn, Marko, Pollard, Andrew, Schlapbach, Luregn J., Shen, Ching-Fen, Tsolia, Maria, Usuf, Effua, Van der Flier, Michiel, Von Both, Ulrich, Yeung, Shunmay, Zavadska, Dace, Zenz, Werner, Wright, Victoria, Carrol, Enitan D., Kaforou, Myrsini, Martinon-Torres, Federico, Fink, Colin, Levin, Michael, Herberg, Jethro, Baumard, Lucas, Bellos, Evangelos, Coin, Lachlan, D'Souza, Giselle, Habgood-Coote, Dominic, Hamilton, Shea, Hoggart, Cllive, Hourmat, Sara, Jackson, Heather, Lin, Naomi, Menikou, Stephanie, Nichols, Samuel, Paz, Ivonne Pena, Powell, Oliver, Vito, Ortensia, Wilson, Clare, Abdulla, Amina, Ali, Ladan, Darnell, Sarah, Jorgensen, Rikke, Maconochie, Ian, Mustafa, Sobia, Persand, Salina, Walsh, Ben, Stevens, Molly, Kim, Nayoung, Kim, Eunjung, Pierce, Benjamin, Dudley, Julia, Richmond, Vivien, Tavliavini, Emma, Liu, Ching-Chuan, Wang, Shih-Min, González, Fernando Álves, Farto, Cristina Balo, Barral-Arca, Ruth, Castro, María Barreiro, Bello, Xabier, Ben García, Mirian, Carnota, Sandra, Cebey-López, Miriam, Curras-Tuala, María José, Suárez, Carlos Durán, Vicente, Luisa García, Gómez-Carballa, Alberto, Rial, Jose Gómez, Iglesias, Pilar Leboráns, Martinón-Torres, Nazareth, Martinón Sánchez, José María, Pérez, Belén Mosquera, Pardo-Seco, Jacobo, Rodríguez, Lidia Piñeiro, Pischedda, Sara, Vázquez, Sara Ray, Rodríguez-Tenreiro, Carmen, Redondo-Collazo, Lorenzo, Ora, Miguel Sadiki, Sallas, Antonio, Fernández, Sonia Serén, Trasorras, Cristina Serén, Iglesias, Marisol Vilas, Balode, Anda, Bãrdzdina, Arta, Deksne, Dãrta, Gardovska, Dace, Grãvele, Dagne, Grope, Ilze, Meiere, Anija, Nokalna, Ieve, Pavãre, Jana, Pučuka, Zanda, Selecka, Katrīna, Svile, Dace, Urbãne, Urzula Nora, Bojang, Kalifa, Zaman, Syed M.A., Anderson, Suzanne, Roca, Anna, Sarr, Isatou, Saidykhan, Momodou, Darboe, Saffiatou, Ceesay, Samba, D'alessandro, Umberto, Borensztajn, Dorine M., Hagedoorn, Nienke N., Tal, Chantal, Zachariasse, Joany, Dik, W., Aebi, Christoph, Berger, Christoph, Wyss, Verena, Usman, Mariama, Giannoni, Eric, Stocker, Martin, Posfay-Barbe, Klara M., Heininger, Ulrich, Bernhard-Stirnemann, Sara, Niederer-Loher, Anita, Kahlert, Christian, Natalucci, Giancarlo, Relly, Christa, Riedel, Thomas, Cocklin, Elizabeth, Jennings, Rebecca, Johnson, Joanne, Leigh, Simon, Newall, Karen, Romaine, Sam, Tambouratzi, Maria, Marmarinos, Antonis, Xagorari, Marietta, Syggelou, Kelly, Spyridis, Nikos, Blackmore, Jennifer, Harrison, Rebekah, Kohlmaier, Benno, Kohlfürst, Daniela S., Zurl, Christoph, Binder, Alexander, Hösele, Susanne, Leitner, Manuel, Pölz, Lena, Rajic, Glorija, Bauchinger, Sebastian, Baumgart, Hinrich, Benesch, Martin, Ceolotto, Astrid, Eber, Ernst, Gallisti, Siegfried, Gores, Gunther, Haidl, Harald, Hauer, Almuthe, Hude, Christa, Keldorfer, Markus, Krenn, Larissa, Pilch, Heidemarie, Pfleger, Andreas, Pfurtscheller, Klaus, Nordberg, Gudrun, Niedrist, Tobias, Rödl, Siegfried, Skrabl-Baumgartner, Andrea, Sperl, Matthias, Stampfer, Laura, Strenger, Volker, Till, Holger, Trobisch, Andreas, Löffler, Sabine, Dewez, Juan Emmanuel, Hibberd, Martin, Bath, David, Miners, Alec, Fitchett, Elizabeth, Wedderburn, Catherine, Meierford, Anne, Leurent, Baptiste, De Jonge, Marien I., van Aerde, Koen, Alkema, Wynand, van den Broek, Bryan, Gloerich, Jolein, Van Gool, Alain J., Henriet, Stefanie, Huijnen, Martijn, Philipsen, Ria, Willems, Esther, Gerrits, G.P.J.M., Van Leur, M., Heidema, J., De Haan, L., Miedema, C.J., Neeleman, C., Obihara, C.C., Tramper-Stranders, G.A., Kandasamy, Rama, Carter, Michael J., O'Connor, Daniel, Bibi, Sagida, Kelly, Dominic F., Gurung, Meeru, Throson, Stephen, Ansari, Imran, Murdoch, David R., Shrestha, Shrijana, Oliver, Zoe, Lim, Emma, Valentine, Lucille, Allen, Karen, Bell, Kathryn, Chan, Adora, Crulley, Stephen, Devine, Kirsty, Fabian, Daniel, King, Sharon, McAlinden, Paul, McDonald, Sam, McDonell, Anne, Pickering, Alisa, Thomson, Evelyn, Wood, Amanda, Wallia, Diane, Woodsford, Phil, Baxter, Frances, Bell, Ashley, Rhodes, Mathew, Agbeko, Rachel, Mackerness, Christine, Baas, Bryan, Kloosterhuis, Lieke, Oosthoek, Wilma, Arif, Tasnim, Bennet, Joshua, Collings, Kalvin, Van der Giessen, Ilona, Martin, Alex, Rashid, Aqeela, Rowlands, Emily, Soon, Joshua, De Vries, Gabriella, van der Velden, Fabian, Martin, Mike, Mistry, Ravi, Zwerenz, Manuela, Buschbeck, Judith, Bidlingmaier, Christoph, Binder, Vera, Danhauser, Katharina, Haas, Nikolaus, Griese, Matthias, Kappler, Matthias, Lurz, Eberhard, Muench, Georg, Reiter, Karl, Schoen, Carola, Pachot, Alexandre, Mommert, Marine, Srovin, Tina Plankar, Bahovec, Natalija, Prunk, Petra, Osterman, Veronika, Avramoska, Tanja, Jongerius, Ilse, van den Berg, J.M., Schonenberg, D., Barendregt, A.M., Pajkrt, D., van der Kuip, M., van Furth, A.M., Sprenkeler, Evelien, Zandstra, Judith, van Mierlo, G., Geissler, J., Rivero-Calle, Irene, Sagmeister, Manfred G., Schweintzger, Nina A., Kuijpers, Taco W., van der Flier, Michiel, and von Both, Ulrich

Published
2023
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4. Impact of infection on proteome-wide glycosylation revealed by distinct signatures for bacterial and viral pathogens

Author

Abdulla, Amina, Aebi, Christoph, van Aerde, Koen, Agbeko, Rachel, Agyeman, Philipp, D’alessandro, Umberto, Ali, Ladan, Alkema, Wynand, Allen, Karen, González, Fernando Álvez, Anderson, Suzanne, Ansari, Imran, Araf, Tasnim, Avramoska, Tanja, Baas, Bryan, Bahovec, Natalija, Farto, Cristina Balo, Balode, Anda, Barendregt, A.M., Barral-Arca, Ruth, Castro, María Barreiro, Bārzdiņa, Arta, Bath, David, Bauchinger, Sebastian, Baumard, Lucas, Baumgart, Hinrich, Baxter, Frances, Bell, Ashley, Bell, Kathryn, Bello, Xabier, Bellos, Evangelos, Benesch, Martin, Ben García, Mirian, Bennet, Joshua, Berger, Christoph, van den Berg, J.M., Bernhard-Stirnemann, Sara, Bibi, Sagida, Bidlingmaier, Christoph, Binder, Alexander, Binder, Vera, Bojang, Kalifa, Borensztajn, Dorine M., von Both, Ulrich, Brengel-Pesce, Karen, van den Broek, Bryan, Buschbeck, Judith, Calvo-Bado, Leo, Carnota, Sandra, Carrol, Enitan D., Carter, Michael J., Cebey-López, Miriam, Ceesay, Samba, Ceolotto, Astrid, Chan, Adora, Cocklin, Elizabeth, Collings, Kalvin, Crulley, Stephen, Cunnington, Aubrey, Curras-Tuala, María José, Danhauser, Katharina, Darboe, Saffiatou, Darnell, Sarah, De, Tisham, Deksne, Dārta, Devine, Kirsty, Dewez, Juan Emmanuel, Dudley, Julia, Suárez, Carlos Durán, Eber, Ernst, Eleftheriou, Irini, Emonts, Marieke, Fabian, Daniel, Feuchtinger, Tobias, Fidler, Katy, Fink, Colin, van der Flier, Michiel, van Furth, A.M., Galassini, Rachel, Gallistl, Siegfried, Vicente, Luisa García, Gardovska, Dace, Geissler, J., Gerrits, G.P.J.M., Giannoni, Eric, van der Giessen, Ilona, Gloerich, Jolein, Gómez-Carballa, Alberto, Rial, Jose Gómez, van Gool, Alain J., Gores, Gunther, Grāvele, Dagne, Griese, Matthias, Grope, Ilze, de Groot, Ronald, Gurung, Meeru, de Haan, L., Haas, Nikolaus, Habgood-Coote, Dominic, Hagedoorn, Nienke N., Haidl, Harald, Hamilton, Shea, Hauer, Almuthe, Heidema, J., Heininger, Ulrich, Henriet, Stefanie, Herberg, Jethro, Hoggart, Clive, Hösele, Susanne, Hourmat, Sara, Hude, Christa, Huijnen, Martijn, Jackson, Heather, Jennings, Rebecca, Johnston, Joanne, de Jonge, Marien I., Jongerius, Ilse, Jorgensen, Rikke, Kaforou, Myrsini, Kahlert, Christian, Kandasamy, Rama, Kappler, Matthias, Keil, Julia, Keldorfer, Markus, Kell, Dominic F., Kim, Eunjung, King, Sharon, Kloosterhuis, Lieke, Kohlfürst, Daniela S., Kohlmaier, Benno, Kolberg, Laura, Kolnik, Mojca, Krenn, Larissa, Kuijpers, Taco, van der Kuip, M., Iglesias, Pilar Leboráns, Leigh, Simon, Leitner, Manuel, van Leur, M., Lim, Emma, Lin, Naomi, Liu, Ching-Chuan, Löffler, Sabine, Lurz, Eberhard, Maconochie, Ian, Mackerness, Christine, Mallet, François, Martinón-Torres, Federico, Marmarinos, Antonis, Martin, Alex, Martin, Mike, Martinón Sánchez, José María, Martinón-Torres, Nazareth, McAlinden, Paul, McDonnell, Anne, McDonald, Sam, Miedema, C.J., Meiere, Anija, Menikou, Stephanie, van Mierlo, G., Miners, Alec, Mistry, Ravi, Moll, Henriëtte A., Mommert, Marine, Pérez, Belén Mosquera, Murdoch, David R., Mustafa, Sobia, Natalucci, Giancarlo, Neeleman, C., Newall, Karen, Nichols, Samuel, Niedrist, Tobias, Niederer-Loher, Anita, Nijman, Ruud, Nokalna, Ieva, Urbāne, Urzula Nora, Nordberg, Gudrun, Obihara, C.C., O'Connor, Daniel, Oosthoek, Wilma, Osterman, Veronika, Pachot, Alexandre, Pajkrt, D., Pardo-Seco, Jacobo, Paulus, Stéphane, Pavāre, Jana, Paz, Ivonne Pena, Persand, Salina, Pfleger, Andreas, Pfurtscheller, Klaus, Philipsen, Ria, Pickering, Ailsa, Pierce, Benjamin, Pilch, Heidemarie, Rodríguez, Lidia Piñeiro, Pischedda, Sara, Srovin, Tina Plankar, Pokorn, Marko, Pollard, Andrew J., Pölz, Lena, Posfay-Barbe, Klara M., Prunk, Petra, Pučuka, Zanda, Rajic, Glorija, Rashid, Aqeela, Redondo-Collazo, Lorenzo, Relly, Christa, Calle, Irene Rivero, Vázquez, Sara Rey, Rhodes, Mathew, Richmond, Vivien, Riedel, Thomas, RocaIsatou Sarr, Anna, Rödl, Siegfried, Rodríguez-Tenreiro, Carmen, Romaine, Sam, Rowlands, Emily, Ora, Miguel Sadiki, Sagmeister, Manfred G., Saidykhan, Momodou, Salas, Antonio, Schlapbach, Luregn J., Schonenberg, D., Secka, Fatou, Selecka, Katrīna, Fernández, Sonia Serén, Trasorras, Cristina Serén, Shah, Priyen, Shen, Ching-Fen, Shrestha, Shrijana, Sidorova, Aleksandra, Skrabl-Baumgartner, Andrea, D’Souza, Giselle, Sperl, Matthias, Sprenkeler, Evelien, Schweintzger, Nina A., Stampfer, Laura, Stevens, Molly, Stocker, Martin, Strenger, Volker, Svile, Dace, Syggelou, Kelly, Tambouratzi, Maria, Tan, Chantal, Tavliavini, Emma, Thomson, Evelyn, Thorson, Stephen, Till, Holger, Tramper-Stranders, G.A., Trobisch, Andreas, Tsolia, Maria, Usuf, Effua, Valentine, Lucille, Vermont, Clementien L., Iglesias, Marisol Vilas, Vincek, Katarina, Voice, Marie, de Vries, Gabriella, Wallia, Diane, Wang, Shih-Min, Willems, Esther, Wilson, Clare, Wood, Amanda, Woodsford, Phil, Wright, Victoria, Xagorari, Marietta, Yeung, Shunmay, Zachariasse, Joany, Zavadska, Dace, Zaman, Syed M.A., Zandstra, Judith, Zenz, Werner, Zurl, Christoph, Zwerenz, Manuela, Suppers, Anouk, van den Heuvel, Lambert P., van de Kar, Nicole, Philipsen, Ria H.L.A., van Dael, Maurice, Wright, Victoria J., Herberg, Jethro A., Torres, Federico Martinon, Levin, Michael, Lefeber, Dirk J., and Wessels, Hans J.C.T.

Published
2023
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5. Multi-tissue transcriptomics of a unique monozygotic discordant twin case of severe progressive osseous heteroplasia

Author

Gómez-Carballa, Alberto, primary, Currás-Tuala, María José, additional, Pischedda, Sara, additional, Cebey-López, Miriam, additional, Gómez-Rial, José, additional, Rivero-Calle, Irene, additional, Pardo-Seco, Jacobo, additional, Bello, Xabier, additional, Viz-Lasheras, Sandra, additional, Justicia-Grande, Antonio, additional, Montoto-Louzao, Julián, additional, Camino-Mera, Alba, additional, Ferreirós-Vidal, Isabel, additional, Fraga, Máximo, additional, Antúnez, José R., additional, Gómez, Rodolfo, additional, Martinón-Torres, Federico, additional, and Salas, Antonio, additional

Published
2024
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6. Diagnostic Test Accuracy of a 2-Transcript Host RNA Signature for Discriminating Bacterial vs Viral Infection in Febrile Children

Author

Herberg, Jethro A, Kaforou, Myrsini, Wright, Victoria J, Shailes, Hannah, Eleftherohorinou, Hariklia, Hoggart, Clive J, Cebey-López, Miriam, Carter, Michael J, Janes, Victoria A, Gormley, Stuart, Shimizu, Chisato, Tremoulet, Adriana H, Barendregt, Anouk M, Salas, Antonio, Kanegaye, John, Pollard, Andrew J, Faust, Saul N, Patel, Sanjay, Kuijpers, Taco, Martinón-Torres, Federico, Burns, Jane C, Coin, Lachlan JM, and Levin, Michael

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Infectious Diseases, Vaccine Related, Genetics, Clinical Research, Emerging Infectious Diseases, Detection, screening and diagnosis, Aetiology, 4.1 Discovery and preclinical testing of markers and technologies, 2.2 Factors relating to the physical environment, 4.2 Evaluation of markers and technologies, Infection, Good Health and Well Being, Anti-Bacterial Agents, Antigens, Area Under Curve, Bacterial Infections, Biomarkers, Child, Preschool, Coinfection, Cytoskeletal Proteins, Diagnosis, Differential, Female, Fever, Gene Expression Profiling, Genetic Markers, Humans, Infant, Logistic Models, Male, Prospective Studies, RNA, Risk, Sensitivity and Specificity, Severity of Illness Index, Virus Diseases, IRIS Consortium, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

ImportanceBecause clinical features do not reliably distinguish bacterial from viral infection, many children worldwide receive unnecessary antibiotic treatment, while bacterial infection is missed in others.ObjectiveTo identify a blood RNA expression signature that distinguishes bacterial from viral infection in febrile children.Design, setting, and participantsFebrile 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.ExposuresA 2-transcript RNA expression signature distinguishing bacterial infection from viral infection was evaluated against clinical and microbiological diagnosis.Main outcomes and measuresDefinite 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.ResultsThe 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, 100%-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 relevanceThis 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

7. Role and Diagnostic Performance of Host Epigenome in Respiratory Morbidity after RSV Infection

Author

Pischedda, Sara, primary, Rivero-Calle, Irene, additional, Gómez-Carballa, Alberto, additional, Cebey-López, Miriam, additional, Barral-Arca, Ruth, additional, Gómez-Rial, Jose, additional, Pardo-Seco, Jacobo, additional, Curras-Tuala, María José, additional, Viz-Lasheras, Sandra, additional, Crujeiras, Ana Belen, additional, Diaz-Lagares, Angel, additional, Martinón-Torres, Federico, additional, and Salas, Antonio, additional

Published
2023
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8. Impact of infection on proteome-wide glycosylation revealed by distinct signatures for bacterial and viral pathogens

Author

Willems, Esther, primary, Gloerich, Jolein, additional, Suppers, Anouk, additional, van der Flier, Michiel, additional, van den Heuvel, Lambert P., additional, van de Kar, Nicole, additional, Philipsen, Ria H.L.A., additional, van Dael, Maurice, additional, Kaforou, Myrsini, additional, Wright, Victoria J., additional, Herberg, Jethro A., additional, Torres, Federico Martinon, additional, Levin, Michael, additional, de Groot, Ronald, additional, van Gool, Alain J., additional, Lefeber, Dirk J., additional, Wessels, Hans J.C.T., additional, de Jonge, Marien I., additional, Abdulla, Amina, additional, Aebi, Christoph, additional, van Aerde, Koen, additional, Agbeko, Rachel, additional, Agyeman, Philipp, additional, D’alessandro, Umberto, additional, Ali, Ladan, additional, Alkema, Wynand, additional, Allen, Karen, additional, González, Fernando Álvez, additional, Anderson, Suzanne, additional, Ansari, Imran, additional, Araf, Tasnim, additional, Avramoska, Tanja, additional, Baas, Bryan, additional, Bahovec, Natalija, additional, Farto, Cristina Balo, additional, Balode, Anda, additional, Barendregt, A.M., additional, Barral-Arca, Ruth, additional, Castro, María Barreiro, additional, Bārzdiņa, Arta, additional, Bath, David, additional, Bauchinger, Sebastian, additional, Baumard, Lucas, additional, Baumgart, Hinrich, additional, Baxter, Frances, additional, Bell, Ashley, additional, Bell, Kathryn, additional, Bello, Xabier, additional, Bellos, Evangelos, additional, Benesch, Martin, additional, Ben García, Mirian, additional, Bennet, Joshua, additional, Berger, Christoph, additional, van den Berg, J.M., additional, Bernhard-Stirnemann, Sara, additional, Bibi, Sagida, additional, Bidlingmaier, Christoph, additional, Binder, Alexander, additional, Binder, Vera, additional, Bojang, Kalifa, additional, Borensztajn, Dorine M., additional, von Both, Ulrich, additional, Brengel-Pesce, Karen, additional, van den Broek, Bryan, additional, Buschbeck, Judith, additional, Calvo-Bado, Leo, additional, Carnota, Sandra, additional, Carrol, Enitan D., additional, Carter, Michael J., additional, Cebey-López, Miriam, additional, Ceesay, Samba, additional, Ceolotto, Astrid, additional, Chan, Adora, additional, Cocklin, Elizabeth, additional, Collings, Kalvin, additional, Crulley, Stephen, additional, Cunnington, Aubrey, additional, Curras-Tuala, María José, additional, Danhauser, Katharina, additional, Darboe, Saffiatou, additional, Darnell, Sarah, additional, De, Tisham, additional, Deksne, Dārta, additional, Devine, Kirsty, additional, Dewez, Juan Emmanuel, additional, Dudley, Julia, additional, Suárez, Carlos Durán, additional, Eber, Ernst, additional, Eleftheriou, Irini, additional, Emonts, Marieke, additional, Fabian, Daniel, additional, Feuchtinger, Tobias, additional, Fidler, Katy, additional, Fink, Colin, additional, van Furth, A.M., additional, Galassini, Rachel, additional, Gallistl, Siegfried, additional, Vicente, Luisa García, additional, Gardovska, Dace, additional, Geissler, J., additional, Gerrits, G.P.J.M., additional, Giannoni, Eric, additional, van der Giessen, Ilona, additional, Gómez-Carballa, Alberto, additional, Rial, Jose Gómez, additional, Gores, Gunther, additional, Grāvele, Dagne, additional, Griese, Matthias, additional, Grope, Ilze, additional, Gurung, Meeru, additional, de Haan, L., additional, Haas, Nikolaus, additional, Habgood-Coote, Dominic, additional, Hagedoorn, Nienke N., additional, Haidl, Harald, additional, Hamilton, Shea, additional, Hauer, Almuthe, additional, Heidema, J., additional, Heininger, Ulrich, additional, Henriet, Stefanie, additional, Herberg, Jethro, additional, Hoggart, Clive, additional, Hösele, Susanne, additional, Hourmat, Sara, additional, Hude, Christa, additional, Huijnen, Martijn, additional, Jackson, Heather, additional, Jennings, Rebecca, additional, Johnston, Joanne, additional, Jongerius, Ilse, additional, Jorgensen, Rikke, additional, Kahlert, Christian, additional, Kandasamy, Rama, additional, Kappler, Matthias, additional, Keil, Julia, additional, Keldorfer, Markus, additional, Kell, Dominic F., additional, Kim, Eunjung, additional, King, Sharon, additional, Kloosterhuis, Lieke, additional, Kohlfürst, Daniela S., additional, Kohlmaier, Benno, additional, Kolberg, Laura, additional, Kolnik, Mojca, additional, Krenn, Larissa, additional, Kuijpers, Taco, additional, van der Kuip, M., additional, Iglesias, Pilar Leboráns, additional, Leigh, Simon, additional, Leitner, Manuel, additional, van Leur, M., additional, Lim, Emma, additional, Lin, Naomi, additional, Liu, Ching-Chuan, additional, Löffler, Sabine, additional, Lurz, Eberhard, additional, Maconochie, Ian, additional, Mackerness, Christine, additional, Mallet, François, additional, Martinón-Torres, Federico, additional, Marmarinos, Antonis, additional, Martin, Alex, additional, Martin, Mike, additional, Martinón Sánchez, José María, additional, Martinón-Torres, Nazareth, additional, McAlinden, Paul, additional, McDonnell, Anne, additional, McDonald, Sam, additional, Miedema, C.J., additional, Meiere, Anija, additional, Menikou, Stephanie, additional, van Mierlo, G., additional, Miners, Alec, additional, Mistry, Ravi, additional, Moll, Henriëtte A., additional, Mommert, Marine, additional, Pérez, Belén Mosquera, additional, Murdoch, David R., additional, Mustafa, Sobia, additional, Natalucci, Giancarlo, additional, Neeleman, C., additional, Newall, Karen, additional, Nichols, Samuel, additional, Niedrist, Tobias, additional, Niederer-Loher, Anita, additional, Nijman, Ruud, additional, Nokalna, Ieva, additional, Urbāne, Urzula Nora, additional, Nordberg, Gudrun, additional, Obihara, C.C., additional, O'Connor, Daniel, additional, Oosthoek, Wilma, additional, Osterman, Veronika, additional, Pachot, Alexandre, additional, Pajkrt, D., additional, Pardo-Seco, Jacobo, additional, Paulus, Stéphane, additional, Pavāre, Jana, additional, Paz, Ivonne Pena, additional, Persand, Salina, additional, Pfleger, Andreas, additional, Pfurtscheller, Klaus, additional, Philipsen, Ria, additional, Pickering, Ailsa, additional, Pierce, Benjamin, additional, Pilch, Heidemarie, additional, Rodríguez, Lidia Piñeiro, additional, Pischedda, Sara, additional, Srovin, Tina Plankar, additional, Pokorn, Marko, additional, Pollard, Andrew J., additional, Pölz, Lena, additional, Posfay-Barbe, Klara M., additional, Prunk, Petra, additional, Pučuka, Zanda, additional, Rajic, Glorija, additional, Rashid, Aqeela, additional, Redondo-Collazo, Lorenzo, additional, Relly, Christa, additional, Calle, Irene Rivero, additional, Vázquez, Sara Rey, additional, Rhodes, Mathew, additional, Richmond, Vivien, additional, Riedel, Thomas, additional, RocaIsatou Sarr, Anna, additional, Rödl, Siegfried, additional, Rodríguez-Tenreiro, Carmen, additional, Romaine, Sam, additional, Rowlands, Emily, additional, Ora, Miguel Sadiki, additional, Sagmeister, Manfred G., additional, Saidykhan, Momodou, additional, Salas, Antonio, additional, Schlapbach, Luregn J., additional, Schonenberg, D., additional, Secka, Fatou, additional, Selecka, Katrīna, additional, Fernández, Sonia Serén, additional, Trasorras, Cristina Serén, additional, Shah, Priyen, additional, Shen, Ching-Fen, additional, Shrestha, Shrijana, additional, Sidorova, Aleksandra, additional, Skrabl-Baumgartner, Andrea, additional, D’Souza, Giselle, additional, Sperl, Matthias, additional, Sprenkeler, Evelien, additional, Schweintzger, Nina A., additional, Stampfer, Laura, additional, Stevens, Molly, additional, Stocker, Martin, additional, Strenger, Volker, additional, Svile, Dace, additional, Syggelou, Kelly, additional, Tambouratzi, Maria, additional, Tan, Chantal, additional, Tavliavini, Emma, additional, Thomson, Evelyn, additional, Thorson, Stephen, additional, Till, Holger, additional, Tramper-Stranders, G.A., additional, Trobisch, Andreas, additional, Tsolia, Maria, additional, Usuf, Effua, additional, Valentine, Lucille, additional, Vermont, Clementien L., additional, Iglesias, Marisol Vilas, additional, Vincek, Katarina, additional, Voice, Marie, additional, de Vries, Gabriella, additional, Wallia, Diane, additional, Wang, Shih-Min, additional, Willems, Esther, additional, Wilson, Clare, additional, Wood, Amanda, additional, Woodsford, Phil, additional, Wright, Victoria, additional, Xagorari, Marietta, additional, Yeung, Shunmay, additional, Zachariasse, Joany, additional, Zavadska, Dace, additional, Zaman, Syed M.A., additional, Zandstra, Judith, additional, Zenz, Werner, additional, Zurl, Christoph, additional, and Zwerenz, Manuela, additional

Published
2023
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9. Host gene expression signatures to identify infection type and organ dysfunction in children evaluated for sepsis: a multicentre cohort study

Author

Schlapbach, Luregn J, Ganesamoorthy, Devika, Wilson, Clare, Raman, Sainath, George, Shane, Snelling, Peter J, Phillips, Natalie, Irwin, Adam, Sharp, Natalie, Le Marsney, Renate, Chavan, Arjun, Hempenstall, Allison, Bialasiewicz, Seweryn, MacDonald, Anna D, Grimwood, Keith, Kling, Jessica C, McPherson, Stephen J, Blumenthal, Antje, Kaforou, Myrsini, Levin, Michael, Herberg, Jethro A, Gibbons, Kristen S, Coin, Lachlan J M, Levin, Michael, Coin, Lachlan, Gormley, Stuart, Hamilton, Shea, Hoggart, Clive, Kaforou, Myrsini, Sancho-Shimizu, Vanessa, Wright, Victoria, Abdulla, Amina, Agapow, Paul, Bartlett, Maeve, Eleftherohorinou, Hariklia, Galassini, Rachel, Inwald, David, Mashbat, Meg, Menikou, Stephanie, Mustafa, Sobia, Nadel, Simon, Rahman, Rahmeen, Shailes, Hannah, Thakker, Clare, Bokhandi, S., Power, Sue, Barham, Heather, Pathan, N., Ridout, Jenna, White, Deborah, Thurston, Sarah, Faust, S., Patel, S., McCorkell, Jenni, Davies, P., Crate, Lindsey, Navarra, Helen, Carter, Stephanie, Ramaiah, R., Patel, Rekha, Tuffrey, Catherine, Gribbin, Andrew, McCready, Sharon, Peters, Mark, Hardy, Katie, Standing, Fran, O'Neill, Lauren, Abelake, Eugenia, Deep, Akash, Nsirim, Eniola, Pollard, Andrew, Willis, Louise, Young, Zoe, Royad, C., White, Sonia, Fortune, Peter-Marc, Hudnott, Phil, Martinón-Torres, Federico, Salas, Antonio, Álvez González, Fernando, Barral-Arca, Ruth, Cebey-López, Miriam, Curras-Tuala, María José, García, Natalia, García Vicente, Luisa, Gómez-Carballa, Alberto, Gómez Rial, Jose, Grela Beiroa, Andrea, Justicia Grande, Antonio, Leboráns Iglesias, Pilar, Martínez Santos, Alba Elena, Martinón-Torres, Nazareth, Martinón Sánchez, José María, Morillo Gutiérrez, Beatriz, Mosquera Pérez, Belén, Obando Pacheco, Pablo, Pardo-Seco, Jacobo, Pischedda, Sara, Rivero-Calle, Irene, Rodríguez-Tenreiro, Carmen, Redondo-Collazo, Lorenzo, Salas Ellacuriaga, Antonio, Fernández, Sonia Serén, del Sol Porto Silva, María, Vega, Ana, Vilanova Trillo, Lucía, Reyes, Susana Beatriz, Cruz León León, María, Navarro Mingorance, Álvaro, Gabaldó Barrio, Xavier, Oñate Vergara, Eider, Concha Torre, Andrés, Vivanco, Ana, Fernández, Reyes, Giménez Sánchez, Francisco, Sánchez Forte, Miguel, Rojo, Pablo, Contreras, J. Ruiz, Palacios, Alba, Epalza Ibarrondo, Cristina, Fernández Cooke, Elizabeth, Navarro, Marisa, Álvarez Álvarez, Cristina, José Lozano, María, Carreras, Eduardo, Brió Sanagustín, Sonia, Neth, Olaf, Martínez Padilla, Mª del Carmen, Prieto Tato, Luis Manuel, Guillén, Sara, Fernández Silveira, Laura, Moreno, David, de Groot, R., Tutu van Furth, A.M., van der Flier, M., Boeddha, N.P., Driessen, G.J.A., Emonts, M., Hazelzet, J.A., Kuijpers, T.W., Pajkrt, D., Sanders, E.A.M., van de Beek, D., van der Ende, A., Philipsen, H.L.A., Adeel, A.O.A., Breukels, M.A., Brinkman, D.M.C., de Korte, C.C.M.M., de Vries, E., de Waal, W.J., Dekkers, R., Dings-Lammertink, A., Doedens, R.A., Donker, A.E., Dousma, M., Faber, T.E., Gerrits, G.P.J.M., Gerver, J.A.M., Heidema, J., Homan-van der Veen, J., Jacobs, M.A.M., Jansen, N.J.G., Kawczynski, P., Klucovska, K., Kneyber, M.C.J., Koopman-Keemink, Y., Langenhorst, V.J., Leusink, J., Loza, B.F., Merth, I.T., Miedema, C.J., Neeleman, C., Noordzij, J.G., Obihara, C.C., van Overbeek- van Gils, A.L.T., Poortman, G.H., Potgieter, S.T., Potjewijd, J., Rosias, P.P.R., Sprong, T., ten Tussher, G.W., Thio, B.J., Tramper-Stranders, G.A., van Deuren, M., van der Meer, H., van Kuppevelt, A.J.M., van Wermeskerken, A.M., Verwijs, W.A., Wolfs, T.F.W., Schlapbach, Luregn J., Agyeman, Philipp, Aebi, Christoph, Giannoni, Eric, Stocker, Martin, Posfay-Barbe, Klara M., Heininger, Ulrich, Bernhard-Stirnemann, Sara, Niederer-Loher, Anita, Kahlert, Christian, Hasters, Paul, Relly, Christa, Baer, Walter, Berger, Christoph, Carrol, Enitan D., Paulus, Stéphane, Frederick, Hannah, Jennings, Rebecca, Johnston, Joanne, Kenwright, Rhian, Fink, Colin G, Pinnock, Elli, Emonts, Marieke, Agbeko, Rachel, Anderson, Suzanne, Secka, Fatou, Bojang, Kalifa, Sarr, Isatou, Kebbeh, Ngange, Sey, Gibbi, Saidykhan, Momodou, Cole, Fatoumata, Thomas, Gilleh, Antonio, Martin, Zenz, Werner, Kohlfürst, Daniela S., Binder, Alexander, Schweintzger, Nina A., Sagmeister, Manfred, Baumgart, Hinrich, Baumgartner, Markus, Behrends, Uta, Biebl, Ariane, Birnbacher, Robert, Blanke, Jan-Gerd, Boelke, Carsten, Breuling, Kai, Brunner, Jürgen, Buller, Maria, Dahlem, Peter, Dietrich, Beate, Eber, Ernst, Elias, Johannes, Emhofer, Josef, Etschmaier, Rosa, Farr, Sebastian, Girtler, Ylenia, Grigorow, Irina, Heimann, Konrad, Ihm, Ulrike, Jaros, Zdenek, Kalhoff, Hermann, Kaulfersch, Wilhelm, Kemen, Christoph, Klocker, Nina, Köster, Bernhard, Kohlmaier, Benno, Komini, Eleni, Kramer, Lydia, Neubert, Antje, Ortner, Daniel, Pescollderungg, Lydia, Pfurtscheller, Klaus, Reiter, Karl, Ristic, Goran, Rödl, Siegfried, Sellner, Andrea, Sonnleitner, Astrid, Sperl, Matthias, Stelzl, Wolfgang, Till, Holger, Trobisch, Andreas, Vierzig, Anne, Vogel, Ulrich, Weingarten, Christina, Welke, Stefanie, Wimmer, Andreas, Wintergerst, Uwe, Wüller, Daniel, Zaunschirm, Andrew, Ziuraite, Ieva, Žukovskaja, Veslava, Hibberd, Martin L., Davila, Sonia, Delany, Isabel, Schlapbach, Luregn J, Raman, Sainath, Sharp, Nathalie, Phillips, Natalie, Irwin, Adam, Balch, Ross, Harley, Amanda, Johnson, Kerry, Sever, Zoe, George, Shane, Grimwood, Keith, Snelling, Peter J, Chavan, Arjun, Kitcatt, Eleanor, Lawton, Luke, Hempenstall, Allison, Pilot, Pelista, Gibbons, Kristen S, Le Marsney, Renate, Blumenthal, Antje, Ganesamoorthy, Devika, Pardo, Carolyn, Kling, Jessica, McPherson, Stephen, MacDonald, Anna D, Bialasiewicz, Seweryn, Pham, Trang, and Coin, Lachlan

Abstract

Sepsis is defined as dysregulated host response to infection that leads to life-threatening organ dysfunction. Biomarkers characterising the dysregulated host response in sepsis are lacking. We aimed to develop host gene expression signatures to predict organ dysfunction in children with bacterial or viral infection.

Published
2024
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11. 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)

Author

Boeddha, Navin P., Schlapbach, Luregn J., Driessen, Gertjan J., Herberg, Jethro A., Rivero-Calle, Irene, Cebey-López, Miriam, Klobassa, Daniela S., Philipsen, Ria, de Groot, Ronald, Inwald, David P., Nadel, Simon, Paulus, Stéphane, Pinnock, Eleanor, Secka, Fatou, Anderson, Suzanne T., Agbeko, Rachel S., Berger, Christoph, Fink, Colin G., Carrol, Enitan D., Zenz, Werner, Levin, Michael, van der Flier, Michiel, Martinón-Torres, Federico, Hazelzet, Jan A., Emonts, Marieke, and on behalf of the EUCLIDS consortium

Published
2018
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12. Febrile illness in high-risk children: a prospective, international observational study

Author

van der Velden, Fabian J. S., de Vries, Gabriella, Martin, Alexander, Lim, Emma, von Both, Ulrich, Kolberg, Laura, Carrol, Enitan D., Khanijau, Aakash, Herberg, Jethro A., De, Tisham, Galassini, Rachel, Kuijpers, Taco W., Martinón-Torres, Federico, Rivero-Calle, Irene, Vermont, Clementien L., Hagedoorn, Nienke N., Pokorn, Marko, Pollard, Andrew J., Schlapbach, Luregn J., Tsolia, Maria, Elefhteriou, Irini, Yeung, Shunmay, Zavadska, Dace, Fink, Colin, Voice, Marie, Zenz, Werner, Kohlmaier, Benno, Agyeman, Philipp K. A., Usuf, Effua, Secka, Fatou, de Groot, Ronald, Levin, Michael, van der Flier, Michiel, Emonts, Marieke, Cunnington, Aubrey, Herberg, Jethro, Kaforou, Myrsini, Wright, Victoria, Baumard, Lucas, Bellos, Evangelos, D’Souza, Giselle, Habgood-Coote, Dominic, Hamilton, Shea, Hoggart, Clive, Hourmat, Sara, Jackson, Heather, Maconochie, Ian, Menikou, Stephanie, Lin, Naomi, Nichols, Samuel, Nijman, Ruud, Powell, Oliver, Pena Paz, Ivonne, Shah, Priyen, Shen, Ching-Fen, Vito, Ortensia, Wilson, Clare, Abdulla, Amina, Ali, Ladan, Darnell, Sarah, Jorgensen, Rikke, Mustafa, Sobia, Persand, Salina, Stevens, Molly M., Kim, Nayoung, Kim, Eunjung, Fidler, Katy, Dudley, Julia, Richmond, Vivien, Tavliavini, Emma, Liu, Ching-Chuan, Wang, Shih-Min, Salas, Antonio, Álvez González, Fernando, Balo Farto, Cristina, Barral-Arca, Ruth, Barreiro Castro, María, Bello, Xabier, García, Mirian Ben, Carnota, Sandra, Cebey-López, Miriam, Curras-Tuala, María José, Durán Suárez, Carlos, García Vicente, Luisa, Gómez-Carballa, Alberto, Gómez Rial, Jose, Leboráns Iglesias, Pilar, Martinón-Torres, Nazareth, Martinón Sánchez, José María, Mosquera Pérez, Belén, Pardo-Seco, Jacobo, Rodríguez, Lidia Piñeiro, Pischedda, Sara, Vázquez, Sara Rey, Rivero Calle, Irene, Rodríguez-Tenreiro, Carmen, Redondo-Collazo, Lorenzo, Sadiki Ora, Miguel, Serén Fernández, Sonia, Serén Trasorras, Cristina, Vilas Iglesias, Marisol, Balode, Anda, Bārzdiņa, Arta, Deksne, Dārta, Gardovska, Dace, Grāvele, Dagne, Grope, Ilze, Meiere, Anija, Nokalna, Ieva, Pavāre, Jana, Pučuka, Zanda, Selecka, Katrīna, Rudzāte, Aleksandra, Svile, Dace, Urbāne, Urzula Nora, Bojang, Kalifa, Zaman, Syed M. A., Anderson, Suzanne, RocaIsatou Sarr, Anna, Saidykhan, Momodou, Darboe, Saffiatou, Ceesay, Samba, D’alessandro, Umberto, Moll, Henriëtte A., Vermont, Clementien L, Borensztajn, Dorine M., Tan, Chantal, Zachariasse, Joany, Dik, W, Agyeman, Philipp KA, Berger, Christoph, Giannoni, Eric, Stocker, Martin, Posfay-Barbe, Klara M, Heininger, Ulrich, Bernhard-Stirnemann, Sara, Niederer-Loher, Anita, Kahlert, Christian R., Natalucci, Giancarlo, Relly, Christa, Riedel, Thomas, Aebi, Christoph, Schlapbach, Luregn J, Carrol, Enitan D, Cocklin, Elizabeth, Jennings, Rebecca, Johnston, Joanne, Leigh, Simon, Lewis-Burke, Nadia, Newall, Karen, Romaine, Sam, Eleftheriou, Irini, Tambouratzi, Maria, Marmarinos, Antonis, Xagorari, Marietta, Syggelou, Kelly, Calvo-Bado, Leo, Schweintzger, Nina A., Sagmeister, Manfred G., Kohlfürst, Daniela S., Zurl, Christoph, Binder, Alexander, Hösele, Susanne, Leitner, Manuel, Pölz, Lena, Rajic, Glorija, Bauchinger, Sebastian, Baumgart, Hinrich, Benesch, Martin, Ceolotto, Astrid, Eber, Ernst, Gallistl, Siegfried, Gores, Gunther, Haidl, Harald, Hauer, Almuthe, Hude, Christa, Keldorfer, Markus, Krenn, Larissa, Pilch, Heidemarie, Pfleger, Andreas, Pfurtscheller, Klaus, Nordberg, Gudrun, Niedrist, Tobias, Rödl, Siegfried, Skrabl-Baumgartner, Andrea, Sperl, Matthias, Stampfer, Laura, Strenger, Volker, Till, Holger, Trobisch, Andreas, Löffler, Sabine, Dewez, Juan Emmanuel, Hibberd, Martin, Bath, David, Miners, Alec, Fitchett, Elizabeth, de Jonge, Marien I., van Aerde, Koen, Alkema, Wynand, van den Broek, Bryan, Gloerich, Jolein, van Gool, Alain J., Henriet, Stefanie, Huijnen, Martijn, Philipsen, Ria, Willems, Esther, Gerrits, G.P.J.M., van Leur, M., Heidema, J., de Haan, L., Miedema, C.J., Neeleman, C., Obihara, C.C., Tramper-Stranders, G.A., Kandasamy, Rama, Paulus, Stéphane, Carter, Michael J., O’Connor, Daniel, Bibi, Sagida, Kelly, Dominic F., Gurung, Meeru, Thorson, Stephen, Ansari, Imran, Murdoch, David R., Shrestha, Shrijana, Oliver, Zoe, Valentine, Lucille, Allen, Karen, Bell, Kathryn, Chan, Adora, Crulley, Stephen, Devine, Kirsty, Fabian, Daniel, King, Sharon, McAlinden, Paul, McDonald, Sam, McDonnell, Anne, Pickering, Ailsa, Thomson, Evelyn, Wood, Amanda, Wallia, Diane, Woodsford, Phil, Baxter, Frances, Bell, Ashley, Rhodes, Mathew, Agbeko, Rachel, Mackerness, Christine, Baas, Bryan, Kloosterhuis, Lieke, Oosthoek, Wilma, Arif, Tasnim, Bennet, Joshua, Collings, Kalvin, van der Giessen, Ilona, Martin, Alex, Rashid, Aqeela, Rowlands, Emily, van der Velden, Fabian, Soon, Joshua, Martin, Mike, Mistry, Ravi, Zwerenz, Manuela, Buschbeck, Judith, Bidlingmaier, Christoph, Binder, Vera, Danhauser, Katharina, Haas, Nikolaus, Griese, Matthias, Feuchtinger, Tobias, Keil, Julia, Kappler, Matthias, Lurz, Eberhard, Muench, Georg, Reiter, Karl, Schoen, Carola, Mallet, François, Brengel-Pesce, Karen, Pachot, Alexandre, Mommert, Marine, Kolnik, Mojca, Vincek, Katarina, Srovin, Tina Plankar, Bahovec, Natalija, Prunk, Petra, Osterman, Veronika, Avramoska, Tanja, Kuijpers, Taco, Jongerius, Ilse, van den Berg, J. M., Schonenberg, D., Barendregt, A. M., Pajkrt, D., van der Kuip, M., van Furth, A. M., Sprenkeler, Evelien, Zandstra, Judith, van Mierlo, G., Geissler, J., consortium, PERFORM, Paediatric Infectious Diseases / Rheumatology / Immunology, AII - Infectious diseases, ARD - Amsterdam Reproduction and Development, and Pediatrics

Subjects
All institutes and research themes of the Radboud University Medical Center, Fever, SDG 3 - Good Health and Well-being, Antibiotics, Paediatric, Pediatrics, Perinatology and Child Health, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], 610 Medicine & health, Infection, 610 Medizin und Gesundheit, Immunocompromised
Abstract

To assess and describe the aetiology and management of febrile illness in children with primary or acquired immunodeficiency at high risk of serious bacterial infection, as seen in emergency departments in tertiary hospitals. Prospective data on demographics, presenting features, investigations, microbiology, management, and outcome of patients within the ‘Biomarker Validation in HR patients’ database in PERFORM, were analysed. Immunocompromised children (N = 492); 94.3% proven/presumed bacterial (N = 164), 66.1% proven/presumed viral (N = 84), and 93.2% unknown bacterial or viral infections (N = 177). Mortality was 1.9% (N = 11) and 87.1% made full recovery (N = 522). Conclusion: The aetiology of febrile illness in immunocompromised children is diverse. In one-third of cases, no cause for the fever will be identified. Justification for standard intravenous antibiotic treatment for every febrile immunocompromised child is debatable, yet effective. Better clinical decision-making tools and new biomarkers are needed for this population. What is Known:• Immunosuppressed children are at high risk for morbidity and mortality of serious bacterial and viral infection, but often present with fever as only clinical symptom.• Current diagnostic measures in this group are not specific to rule out bacterial infection, and positivity rates of microbiological cultures are low. What is New:• Febrile illness and infectious complications remain a significant cause of mortality and morbidity in HR children, yet management is effective.• The aetiology of febrile illness in immunocompromised children is diverse, and development of pathways for early discharge or cessation of intravenous antibiotics is debatable, and requires better clinical decision-making tools and biomarkers.

Published
2022

13. Role and Diagnostic Performance of Host Epigenome in Respiratory Morbidity after RSV Infection: The EPIRESVi Study

Author

Pischedda, Sara, Rivero-Calle, Irene, Gómez-Carballa, Alberto, Cebey-López, Miriam, Barral-Arca, Ruth, Gómez-Rial, Jose, Pardo-Seco, Jacobo, Curras-Tuala, María-José, Viz-Lasheras, Sandra, Bello, Xabier, Crujeiras, Ana B., Diaz-Lagares, Angel, González-López, María Teresa, Martinón-Torres, Federico, and Salas, Antonio

Subjects
Epigenome, Immunology, Disease Progression, Humans, Immunology and Allergy, DNA, Prospective Studies, Respiratory Syncytial Virus Infections, Morbidity, Asthma, Respiratory Sounds
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.

Published
2022
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14. A multi-tissue study of immune gene expression profiling highlights the key role of the nasal epithelium in COVID-19 severity

Author

Universidade de Santiago de Compostela. Departamento de Ciencias Forenses, Anatomía Patolóxica, Xinecoloxía e Obstetricia, e Pediatría, Gómez Carballa, Alberto, Rivero Calle, Irene, Pardo Seco, Jacobo José, Gómez Rial, José, Rivero Velasco, Carmen, Rodríguez Núñez, Nuria, Barbeito Castiñeiras, Gema, Perez Freixo, Hugo, Cebey López, Miriam, Barral Arca, Ruth, Rodríguez-Tenreiro Sánchez, Carmen, Dacosta Urbieta, Ana Isabel, Bello, Xabier, Pischedda, Sara, Currás Tuala, María José, Viz Lasheras, Sandra, Martinón Torres, Federico, Salas Ellacuriaga, Antonio, Gen Covid Study Group, Universidade de Santiago de Compostela. Departamento de Ciencias Forenses, Anatomía Patolóxica, Xinecoloxía e Obstetricia, e Pediatría, Gómez Carballa, Alberto, Rivero Calle, Irene, Pardo Seco, Jacobo José, Gómez Rial, José, Rivero Velasco, Carmen, Rodríguez Núñez, Nuria, Barbeito Castiñeiras, Gema, Perez Freixo, Hugo, Cebey López, Miriam, Barral Arca, Ruth, Rodríguez-Tenreiro Sánchez, Carmen, Dacosta Urbieta, Ana Isabel, Bello, Xabier, Pischedda, Sara, Currás Tuala, María José, Viz Lasheras, Sandra, Martinón Torres, Federico, Salas Ellacuriaga, Antonio, and Gen Covid Study Group

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 di

Published
2022

15. Osteoarticular Infections in Pediatric Hospitals in Europe:A Prospective Cohort Study From the EUCLIDS Consortium

Author

Trobisch, Andreas, Schweintzger, Nina A., Kohlfürst, Daniela S., Sagmeister, Manfred G., Sperl, Matthias, Grisold, Andrea J., Feierl, Gebhard, Herberg, Jethro A., Carrol, Enitan D., Paulus, Stephane C., Emonts, Marieke, van der Flier, Michiel, de Groot, Ronald, Cebey-López, Miriam, Rivero-Calle, Irene, Boeddha, Navin P., Agapow, Paul Michael, Secka, Fatou, Anderson, Suzanne T., Behrends, Uta, Wintergerst, Uwe, Reiter, Karl, Martinon-Torres, Federico, Levin, Michael, Zenz, Werner, Trobisch, Andreas, Schweintzger, Nina A., Kohlfürst, Daniela S., Sagmeister, Manfred G., Sperl, Matthias, Grisold, Andrea J., Feierl, Gebhard, Herberg, Jethro A., Carrol, Enitan D., Paulus, Stephane C., Emonts, Marieke, van der Flier, Michiel, de Groot, Ronald, Cebey-López, Miriam, Rivero-Calle, Irene, Boeddha, Navin P., Agapow, Paul Michael, Secka, Fatou, Anderson, Suzanne T., Behrends, Uta, Wintergerst, Uwe, Reiter, Karl, Martinon-Torres, Federico, Levin, Michael, and Zenz, Werner

Abstract

Background: Pediatric osteoarticular infections (POAIs) are serious diseases requiring early diagnosis and treatment. Methods: In 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. Results: A 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. Conclusion: POAIs 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.

Published
2022

16. A multi-tissue study of immune gene expression profiling highlights the key role of the nasal epithelium in COVID-19 severity

Author

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

Subjects
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

Published
2022

17. Corrigendum: Case Report: Two Monochorionic Twins With a Critically Different Course of Progressive Osseous Heteroplasia

Author

Justicia-Grande, Antonio José, primary, Gómez-Ríal, Jose, additional, Rivero-Calle, Irene, additional, Pischedda, Sara, additional, Curras-Tuala, María José, additional, Gómez-Carballa, Alberto, additional, Cebey-López, Miriam, additional, Pardo-Seco, Jacobo, additional, Méndez-Gallart, Roberto, additional, Fernández-Seara, María José, additional, Salas, Antonio, additional, and Martinón-Torres, Federico, additional

Published
2021
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18. Case Report: Two Monochorionic Twins With a Critically Different Course of Progressive Osseous Heteroplasia

Author

Justicia-Grande, Antonio José, primary, Gómez-Ríal, Jose, additional, Rivero-Calle, Irene, additional, Pischedda, Sara, additional, Curras-Tuala, María José, additional, Gómez-Carballa, Alberto, additional, Cebey-López, Miriam, additional, Pardo-Seco, Jacobo, additional, Méndez-Gallart, Roberto, additional, Fernández-Seara, María José, additional, Salas, Antonio, additional, and Martinón-Torres, Federico, additional

Published
2021
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19. Case Report: Two Monochorionic Twins With a Critically Different Course of Progressive Osseus Heteroplasia

Author

Universidade de Santiago de Compostela. Departamento de Ciencias Forenses, Anatomía Patolóxica, Xinecoloxía e Obstetricia, e Pediatría, Justicia Grande, Antonio, Gómez Rial, José, Rivero Calle, Irene, Pischedda, Sara, Currás Tuala, María José, Gómez Carballa, Alberto, Cebey López, Miriam, Pardo Seco, Jacobo José, Méndez Gallart, Roberto, Fernández Seara, María José, Salas Ellacuriaga, Antonio, Martinón Torres, Federico, Universidade de Santiago de Compostela. Departamento de Ciencias Forenses, Anatomía Patolóxica, Xinecoloxía e Obstetricia, e Pediatría, Justicia Grande, Antonio, Gómez Rial, José, Rivero Calle, Irene, Pischedda, Sara, Currás Tuala, María José, Gómez Carballa, Alberto, Cebey López, Miriam, Pardo Seco, Jacobo José, Méndez Gallart, Roberto, Fernández Seara, María José, Salas Ellacuriaga, Antonio, and Martinón Torres, Federico

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

Published
2021

22. A Meta-Analysis of Multiple Whole Blood Gene Expression Data Unveils a Diagnostic Host-Response Transcript Signature for Respiratory Syncytial Virus

Author

Universidade de Santiago de Compostela. Departamento de Ciencias Forenses, Anatomía Patolóxica, Xinecoloxía e Obstetricia, e Pediatría, Barral Arca, Ruth, Gómez Carballa, Alberto, Cebey López, Miriam, Bello Paderne, Xabier, Martinón Torres, Federico, Salas Ellacuriaga, Antonio, Universidade de Santiago de Compostela. Departamento de Ciencias Forenses, Anatomía Patolóxica, Xinecoloxía e Obstetricia, e Pediatría, Barral Arca, Ruth, Gómez Carballa, Alberto, Cebey López, Miriam, Bello Paderne, Xabier, Martinón Torres, Federico, and Salas Ellacuriaga, Antonio

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

Published
2020

23. Analysis of a Real-World Cohort of Metastatic Breast Cancer Patients Shows Circulating Tumor Cell Clusters (CTC-clusters) as Predictors of Patient Outcomes

Author

Universidade de Santiago de Compostela. Departamento de Cirurxía e Especialidades Médico-Cirúrxicas, Costa, Clotilde, Muinelo Romay, Laura, Cebey López, Miriam, Pereira Veiga, Tais, Martínez Pena, Inés, Abreu Rodríguez, Manuel, Abalo, Alicia, Lago Lestón, Ramón, Abuín, Carmen, Palacios, Patricia, Cueva, Juan, Piñeiro Cid, Roberto, López López, Rafael, Universidade de Santiago de Compostela. Departamento de Cirurxía e Especialidades Médico-Cirúrxicas, Costa, Clotilde, Muinelo Romay, Laura, Cebey López, Miriam, Pereira Veiga, Tais, Martínez Pena, Inés, Abreu Rodríguez, Manuel, Abalo, Alicia, Lago Lestón, Ramón, Abuín, Carmen, Palacios, Patricia, Cueva, Juan, Piñeiro Cid, Roberto, and López López, Rafael

Abstract

Circulating tumor cell (CTC) enumeration has emerged as a powerful biomarker for the assessment of prognosis and the response to treatment in metastatic breast cancer (MBC). Moreover, clinical evidences show that CTC-cluster counts add prognostic information to CTC enumeration, however, their significance is not well understood, and more clinical evidences are needed. We aim to evaluate the prognostic value of longitudinally collected single CTCs and CTC-clusters in a heterogeneous real-world cohort of 54 MBC patients. Blood samples were longitudinally collected at baseline and follow up. CTC and CTC-cluster enumeration was performed using the CellSearch® system. Associations with progression-free survival (PFS) and overall survival (OS) were evaluated using Cox proportional hazards modelling. Elevated CTC counts and CTC-clusters at baseline were significantly associated with a shorter survival time. In joint analysis, patients with high CTC counts and CTC-cluster at baseline were at a higher risk of progression and death, and longitudinal analysis showed that patients with CTC-clusters had significantly shorter survival compared to patients without clusters. Moreover, patients with CTC-cluster of a larger size were at a higher risk of death. A longitudinal analysis of a real-world cohort of MBC patients indicates that CTC-clusters analysis provides additional prognostic value to single CTC enumeration, and that CTC-cluster size correlates with patient outcome

Published
2020

24. RNA-Seq Data-Mining Allows the Discovery of Two Long Non-Coding RNA Biomarkers of Viral Infection in Humans

Author

Universidade de Santiago de Compostela. Departamento de Ciencias Forenses, Anatomía Patolóxica, Xinecoloxía e Obstetricia, e Pediatría, Barral Arca, Ruth, Gómez Carballa, Alberto, Cebey López, Miriam, Currás Tuala, María José, Pischedda, Sara, Viz Lasheras, Sandra, Bello Paderne, Xabier, Martinón Torres, Federico, Salas Ellacuriaga, Antonio, Universidade de Santiago de Compostela. Departamento de Ciencias Forenses, Anatomía Patolóxica, Xinecoloxía e Obstetricia, e Pediatría, Barral Arca, Ruth, Gómez Carballa, Alberto, Cebey López, Miriam, Currás Tuala, María José, Pischedda, Sara, Viz Lasheras, Sandra, Bello Paderne, Xabier, Martinón Torres, Federico, and Salas Ellacuriaga, Antonio

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

Published
2020

25. Host Transcriptomic Response Following Administration of Rotavirus Vaccine in Infants’ Mimics Wild Type Infection

Author

Gómez-Carballa, Alberto, primary, Barral-Arca, Ruth, additional, Cebey-López, Miriam, additional, Currás-Tuala, Maria José, additional, Pischedda, Sara, additional, Gómez-Rial, José, additional, Habgood-Coote, Dominic, additional, Herberg, Jethro A., additional, Kaforou, Myrsini, additional, Martinón-Torres, Federico, additional, and Salas, Antonio, additional

Published
2021
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26. Increased Serum Levels of sCD14 and sCD163 Indicate a Preponderant Role for Monocytes in COVID-19 Immunopathology

Author

Gómez-Rial, Jose, primary, Currás-Tuala, Maria José, additional, Rivero-Calle, Irene, additional, Gómez-Carballa, Alberto, additional, Cebey-López, Miriam, additional, Rodríguez-Tenreiro, Carmen, additional, Dacosta-Urbieta, Ana, additional, Rivero-Velasco, Carmen, additional, Rodríguez-Núñez, Nuria, additional, Trastoy-Pena, Rocio, additional, Rodríguez-García, Javier, additional, Salas, Antonio, additional, and Martinón-Torres, Federico, additional

Published
2020
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29. Whole Exome Sequencing Identifies New Host Genomic Susceptibility Factors in Empyema Caused by Streptococcus pneumoniae in Children: A Pilot Study

Author

Salas Ellacuriaga, Antonio, Pardo Seco, Jacobo José, Barral Arca, Ruth, Cebey López, Miriam, Gómez Carballa, Alberto, Rivero Calle, Irene, Pischedda, Sara, Currás Tuala, María José, Amigo Lechuga, Jorge, Gómez Rial, Jose, Martinón Torres, Federico, GENDRES network, and Universidade de Santiago de Compostela. Departamento de Ciencias Forenses, Anatomía Patolóxica, Xinecoloxía e Obstetricia, e Pediatría

Subjects
0301 basic medicine, lcsh:QH426-470, pediatrics, infectious disease, Single-nucleotide polymorphism, Biology, medicine.disease_cause, Pediatrics, Article, whole exome sequencing, 03 medical and health sciences, Next generation sequencing, Streptococcus pneumoniae, Genetics, medicine, SNP, 1000 Genomes Project, Genetics (clinical), Exome sequencing, next generation sequencing, Infectious disease, Massive parallel sequencing, parallel sequencing, Whole exome sequencing, medicine.disease, lcsh:Genetics, 030104 developmental biology, Parallel sequencing, Infectious disease (medical specialty), Pneumococcal pneumonia, Transcriptome, transcriptome
Abstract

Pneumonia is the leading cause of death amongst infectious diseases. Streptococcus pneumoniae is responsible for about 25% of pneumonia cases worldwide, and it is a major cause of childhood mortality. We carried out a whole exome sequencing (WES) study in eight patients with complicated cases of pneumococcal pneumonia (empyema). An initial assessment of statistical association of WES variation with pneumonia was carried out using data from the 1000 Genomes Project (1000G) for the Iberian Peninsula (IBS) as reference controls. Pseudo-replication statistical analyses were carried out using different European control groups. Association tests pointed to single nucleotide polymorphism (SNP) rs201967957 (gene MEIS1; chromosome 2; p-valueIBS = 3.71 × 10−13) and rs576099063 (gene TSPAN15; chromosome 10; p-valueIBS = 2.36 × 10−8) as the best candidate variants associated to pneumococcal pneumonia. A burden gene test of pathogenicity signaled four genes, namely, OR9G9, MUC6, MUC3A and APOB, which carry significantly increased pathogenic variation when compared to controls. By analyzing various transcriptomic data repositories, we found strong supportive evidence for the role of MEIS1, TSPAN15 and APOBR (encoding the receptor of the APOB protein) in pneumonia in mouse and human models. Furthermore, the association of the olfactory receptor gene OR9G9 has recently been related to some viral infectious diseases, while the role of mucin genes (MUC6 and MUC3A), encoding mucin glycoproteins, are well-known factors related to chronic obstructive airway disease. WES emerges as a promising technique to disentangle the genetic basis of host genome susceptibility to infectious respiratory diseases This study received support from the Instituto de Salud Carlos III (Proyecto de Investigación en Salud, Acción Estratégica en Salud): project GePEM ISCIII/PI16/01478/Cofinanciado FEDER) (A.S.) and project ReSVinext ISCIII/PI16/01569/Cofinanciado FEDER (F.M.-T.); Consellería de Sanidade, Xunta de Galicia (RHI07/2-intensificación actividad investigadora, PS09749 and 10PXIB918184PR), Instituto de Salud Carlos III (Intensificación de la actividad investigadora 2007–2012, PI16/01569), Fondo de Investigación Sanitaria (FIS; PI070069/PI1000540) del Plan Nacional de I + D + I and ‘Fondos FEDER’ (F.M.-T.), and 2016-PG071 Consolidación e Estructuración REDES 2016GI-1344 G3VIP (Grupo Gallego de Genética Vacunas Infecciones y Pediatría, ED341D R2016/021) (A.S. and F.M.T) SI

Published
2018
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30. Lifestyle and comorbid conditions as risk factors for community-acquired pneumonia in outpatient adults (NEUMO-ES-RISK project)

Author

Rivero-Calle, Irene, primary, Cebey-López, Miriam, additional, Pardo-Seco, Jacobo, additional, Yuste, José, additional, Redondo, Esther, additional, Vargas, Diego A, additional, Mascarós, Enrique, additional, Díaz-Maroto, Jose Luis, additional, Linares-Rufo, Manuel, additional, Jimeno, Isabel, additional, Gil, Angel, additional, Molina, Jesus, additional, Ocaña, Daniel, additional, and Martinón-Torres, Federico, additional

Published
2019
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31. 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)

Author

Boeddha, Navin P, Schlapbach, Luregn J, Driessen, Gertjan J, Herberg, Jethro A, Rivero-Calle, Irene, Cebey-López, Miriam, Klobassa, Daniela S, Philipsen, Ria, de Groot, Ronald, Inwald, David P, Nadel, Simon, Paulus, Stéphane, Pinnock, Eleanor, Secka, Fatou, Anderson, Suzanne T, Agbeko, Rachel S, Berger, Christoph; https://orcid.org/0000-0002-1730-8824, Fink, Colin G, Carrol, Enitan D, Zenz, Werner, Levin, Michael, van der Flier, Michiel, Martinón-Torres, Federico, Hazelzet, Jan A, Emonts, Marieke, Boeddha, Navin P, Schlapbach, Luregn J, Driessen, Gertjan J, Herberg, Jethro A, Rivero-Calle, Irene, Cebey-López, Miriam, Klobassa, Daniela S, Philipsen, Ria, de Groot, Ronald, Inwald, David P, Nadel, Simon, Paulus, Stéphane, Pinnock, Eleanor, Secka, Fatou, Anderson, Suzanne T, Agbeko, Rachel S, Berger, Christoph; https://orcid.org/0000-0002-1730-8824, Fink, Colin G, Carrol, Enitan D, Zenz, Werner, Levin, Michael, van der Flier, Michiel, Martinón-Torres, Federico, Hazelzet, Jan A, and Emonts, Marieke

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 < 0.01) and illness severity as measured by Pediatric Index of Mortality (PIM2) score (mortality OR 2.8, 95% CI 1.3-6.1, P < 0.01; disability OR 3.4, 95% CI 1.8-6.4, P < 0.001). CONCLUSIONS Despite widespread immunization campaigns, invasive bacterial disease remains responsible for substantial morbidity and mortality in critically ill chi

Published
2018

32. Whole Exome Sequencing Identifies New Host Genomic Susceptibility Factors in Empyema Caused by Streptococcus pneumoniae in Children: A Pilot Study

Author

Universidade de Santiago de Compostela. Departamento de Ciencias Forenses, Anatomía Patolóxica, Xinecoloxía e Obstetricia, e Pediatría, Salas Ellacuriaga, Antonio, Pardo Seco, Jacobo José, Barral Arca, Ruth, Cebey López, Miriam, Gómez Carballa, Alberto, Rivero Calle, Irene, Pischedda, Sara, Currás Tuala, María José, Amigo Lechuga, Jorge, Gómez Rial, Jose, Martinón Torres, Federico, GENDRES network, Universidade de Santiago de Compostela. Departamento de Ciencias Forenses, Anatomía Patolóxica, Xinecoloxía e Obstetricia, e Pediatría, Salas Ellacuriaga, Antonio, Pardo Seco, Jacobo José, Barral Arca, Ruth, Cebey López, Miriam, Gómez Carballa, Alberto, Rivero Calle, Irene, Pischedda, Sara, Currás Tuala, María José, Amigo Lechuga, Jorge, Gómez Rial, Jose, Martinón Torres, Federico, and GENDRES network

Abstract

Pneumonia is the leading cause of death amongst infectious diseases. Streptococcus pneumoniae is responsible for about 25% of pneumonia cases worldwide, and it is a major cause of childhood mortality. We carried out a whole exome sequencing (WES) study in eight patients with complicated cases of pneumococcal pneumonia (empyema). An initial assessment of statistical association of WES variation with pneumonia was carried out using data from the 1000 Genomes Project (1000G) for the Iberian Peninsula (IBS) as reference controls. Pseudo-replication statistical analyses were carried out using different European control groups. Association tests pointed to single nucleotide polymorphism (SNP) rs201967957 (gene MEIS1; chromosome 2; p-valueIBS = 3.71 × 10−13) and rs576099063 (gene TSPAN15; chromosome 10; p-valueIBS = 2.36 × 10−8) as the best candidate variants associated to pneumococcal pneumonia. A burden gene test of pathogenicity signaled four genes, namely, OR9G9, MUC6, MUC3A and APOB, which carry significantly increased pathogenic variation when compared to controls. By analyzing various transcriptomic data repositories, we found strong supportive evidence for the role of MEIS1, TSPAN15 and APOBR (encoding the receptor of the APOB protein) in pneumonia in mouse and human models. Furthermore, the association of the olfactory receptor gene OR9G9 has recently been related to some viral infectious diseases, while the role of mucin genes (MUC6 and MUC3A), encoding mucin glycoproteins, are well-known factors related to chronic obstructive airway disease. WES emerges as a promising technique to disentangle the genetic basis of host genome susceptibility to infectious respiratory diseases

Published
2018

33. IMPACT OF MODERATE VACCINATION RATE AGAINST ROTAVIRUS DURING 9 YEARS IN THE GASTROENTERITIS HOSPITALIZATION RATE

Author

Martinón-Torres, Federico, Pardo-Seco, Jacobo, Justicia-Grande, Antonio, and Cebey-López, Miriam

Abstract

Rotavirus (RV) vaccines were introduced in Spain between 2006 and 2007, and despite moderate coverage, it showed high effectiveness in the short term. We aim to evaluate the impact of moderate vaccination (22.3-49.3%) during 9 years in all-cause (AC) acute gastroenteritis (AGE) and RV-caused AGE hospitalization rates in Galicia (north-west Spain) in children younger than 5 years.In this ecological retrospective study, data have been obtained from Conjunto Mu00ednimo Bu00e1sico de Datos (CMBD; www.iasist.com) database. The study population considers children younger 5 years old admitted between July 2003 and June 2015. We have considered AGE (ICD-9 code from 001 to 009), and more specifically AGE caused by RV (RV-AGE, code ICD-9 008.6). Population data has been obtained from Instituto Galego de Estatu00edstica (www.ige.eu). Yearly hospitalization rates were analyzed excluding year 2007 (when the vaccine was introduced).A significant decrease in hospitalization rates was observed since RV vaccine introduction when comparing with the pre-vaccination period for children younger than 5 years old for both AGE (from 19.0% in 2014 to 50.3% in 2008) (Figure A) and RV-AGE (from 26.3% in 2014, to 51.1% in 2008) (Figure B). In the last years the magnitude of this decrease is smaller, which could be related to different factors from test sensibility to duration of herd protection or disease seasonality.Vaccination against RV, even with moderate -but sustained- vaccination coverage, shows a high effectiveness in relation to hospitalization by AGE and RV-AGE. The present study reinforces the convenience of including RV vaccine in the Spanish immunization schedule.

Published
2017

34. Life-threatening infections in children in Europe (the EUCLIDS Project): a prospective cohort study

Author

Martinón-Torres, Federico, primary, Salas, Antonio, additional, Rivero-Calle, Irene, additional, Cebey-López, Miriam, additional, Pardo-Seco, Jacobo, additional, Herberg, Jethro A, additional, Boeddha, Navin P, additional, Klobassa, Daniela S, additional, Secka, Fatou, additional, Paulus, Stephane, additional, de Groot, Ronald, additional, Schlapbach, Luregn J, additional, Driessen, Gertjan J, additional, Anderson, Suzanne T, additional, Emonts, Marieke, additional, Zenz, Werner, additional, Carrol, Enitan D, additional, Van der Flier, Michiel, additional, Levin, Michael, additional, Coin, Lachlan, additional, Gormley, Stuart, additional, Hamilton, Shea, additional, Herberg, Jethro, additional, Hourmat, Bernardo, additional, Hoggart, Clive, additional, Kaforou, Myrsini, additional, Sancho-Shimizu, Vanessa, additional, Wright, Victoria, additional, Abdulla, Amina, additional, Agapow, Paul, additional, Bartlett, Maeve, additional, Bellos, Evangelos, additional, Eleftherohorinou, Hariklia, additional, Galassini, Rachel, additional, Inwald, David, additional, Mashbat, Meg, additional, Menikou, Stefanie, additional, Mustafa, Sobia, additional, Nadel, Simon, additional, Rahman, Rahmeen, additional, Thakker, Clare, additional, Bokhandi, Sumit, additional, Power, Sue, additional, Barham, Heather, additional, Pathan, Nazima, additional, Ridout, Jenna, additional, White, Deborah, additional, Thurston, Sarah, additional, Faust, Saul, additional, Patel, Sanjay, additional, McCorkell, Jenni, additional, Davies, Patrick, additional, Crate, Lindsey, additional, Navarra, Helen, additional, Carter, Stephanie, additional, Ramaiah, Raghu, additional, Patel, Rekha, additional, Tuffrey, Catherine, additional, Gribbin, Andrew, additional, McCready, Sharon, additional, Peters, Mark, additional, Hardy, Katie, additional, Standing, Fran, additional, O'Neill, Lauren, additional, Abelake, Eugenia, additional, Deep, Akash, additional, Nsirim, Eniola, additional, Pollard, Andrew, additional, Willis, Louise, additional, Young, Zoe, additional, Royad, C, additional, White, Sonia, additional, Fortune, Peter Marc, additional, Hudnott, Phil, additional, Martinón-Torres, Federico, additional, Salas Ellacuriaga, Antonio, additional, Álvez González, Fernando, additional, Barral-Arca, Ruth, additional, Curras-Tuala, María José, additional, García, Natalia, additional, García Vicente, Luisa, additional, Gómez-Carballa, Alberto, additional, Gómez Rial, Jose, additional, Grela Beiroa, Andrea, additional, Justicia Grande, Antonio, additional, Leboráns Iglesias, Pilar, additional, Martínez Santos, Alba Elena, additional, Martinón-Torres, Nazareth, additional, Martinón Sánchez, José María, additional, Morillo Gutiérrez, Beatriz, additional, Mosquera Pérez, Belén, additional, Obando Pacheco, Pablo, additional, Pischedda, Sara, additional, Rodríguez-Tenreiro, Carmen, additional, Redondo-Collazo, Lorenzo, additional, Serén Fernández, Sonia, additional, Porto Silva, María del Sol, additional, Vega, Ana, additional, Vilanova Trillo, Lucía, additional, Reyes, Susana Beatriz, additional, León León, María Cruz, additional, Navarro Mingorance, Álvaro, additional, Gabaldó Barrios, Xavier, additional, Oñate Vergara, Eider, additional, Concha Torre, Andrés, additional, Vivanco, Ana, additional, Fernández, Reyes, additional, Giménez Sánchez, Francisco, additional, Sánchez Forte, Miguel, additional, Rojo, Pablo, additional, Ruiz Contreras, Jesús, additional, Palacios, Alba, additional, Epalza Ibarrondo, Cristina, additional, Fernández Cooke, Elizabeth, additional, Navarro, Marisa, additional, Álvarez Álvarez, Cristina, additional, Lozano, María José, additional, Carreras, Eduardo, additional, Brió Sanagustín, Sonia, additional, Neth, Olaf, additional, Martínez Padilla, María del Carmen, additional, Prieto Tato, Luis Manuel, additional, Guillén, Sara, additional, Fernández Silveira, Laura, additional, Moreno, David, additional, van Furth, A. Marceline, additional, van der Flier, Michiel, additional, Boeddha, Navin Prekash, additional, Driessen, Gertjan JA, additional, Hazelzet, Jan A, additional, Kuijpers, Taco W, additional, Pajkrt, Dasja, additional, Sanders, Elisabeth AM, additional, van de Beek, Diederik, additional, van der Ende, Arie, additional, Philipsen, Ria LA, additional, Adeel, Abdul OA, additional, Breukels, Meike A, additional, Brinkman, Danielle MC, additional, de Korte, Carla CMM, additional, de Vries, Esther, additional, de Waal, Wouter J, additional, Dekkers, Roel, additional, Dings-Lammertink, Anouk, additional, Doedens, Rienus A, additional, Donker, Albertine E, additional, Dousma, Mieke, additional, Faber, Tina E, additional, Gerrits, G Peter JM, additional, Gerver, Jan AM, additional, Heidema, Jojanneke, additional, Homan-van der Veen, Jenneke, additional, Jacobs, Monique AM, additional, Jansen, Nicolaas JG, additional, Kawczynski, Pawel, additional, Klucovska, Kristine, additional, Kneyber, Martin CJ, additional, Koopman-Keemink, Yvonne, additional, Langenhorst, Veerle J, additional, Leusink, José, additional, Loza, Bettina F, additional, Merth, Istvan T, additional, Miedema, Carien J, additional, Neeleman, Chris, additional, Noordzij, Jeroen G, additional, Obihara, Charles C, additional, van Overbeek - van Gils, A Lidy T, additional, Poortman, Geriska H, additional, Potgieter, Steph T, additional, Potjewijd, Joke, additional, Rosias, Philippe PR, additional, Sprong, Tom, additional, ten Tussher, Gavin W, additional, Thio, Boony J, additional, Tramper-Stranders, Gerdien A, additional, van Deuren, Marcel, additional, van der Meer, Henny, additional, van Kuppevelt, Andre JM, additional, van Wermeskerken, Anne-Marie, additional, Verwijs, Wim A, additional, Wolfs, Tom FW, additional, Schlapbach, Luregn Jan, additional, Agyeman, Philipp, additional, Aebi, Christoph, additional, Berger, Christoph, additional, Giannoni, Eric, additional, Stocker, Martin, additional, Posfay-Barbe, Klara M, additional, Heininger, Ulrich, additional, Bernhard-Stirnemann, Sara, additional, Niederer-Loher, Anita, additional, Kahlert, Christian, additional, Hasters, Paul, additional, Relly, Christa, additional, Baer, Walter, additional, Carrol, Enitan, additional, Paulus, Stéphane, additional, Frederick, Hannah, additional, Jennings, Rebecca, additional, Johnston, Joanne, additional, Kenwright, Rhian, additional, Fink, Colin G, additional, Pinnock, Elli, additional, Agbeko, Rachel Sarah, additional, Bojang, Kalifa A, additional, Sarr, Isatou, additional, Kebbeh, Ngange, additional, Sey, Gibbi, additional, Saidykhan, Momodou, additional, Cole, Fatoumata, additional, Thomas, Gilleh, additional, Antonio, Martin, additional, Klobassa, Daniela Sabine, additional, Binder, Alexander, additional, Schweintzger, Nina Alexandra, additional, Sagmeister, Manfred, additional, Baumgart, Hinrich, additional, Baumgartner, Markus, additional, Behrends, Uta, additional, Biebl, Ariane, additional, Birnbacher, Robert, additional, Blanke, Jan-Gerd, additional, Boelke, Carsten, additional, Breuling, Kai, additional, Brunner, Jürgen, additional, Buller, Maria, additional, Dahlem, Peter, additional, Dietrich, Beate, additional, Eber, Ernst, additional, Elias, Johannes, additional, Emhofer, Josef, additional, Etschmaier, Rosa, additional, Farr, Sebastian, additional, Girtler, Ylenia, additional, Grigorow, Irina, additional, Heimann, Konrad, additional, Ihm, Ulrike, additional, Jaros, Zdenek, additional, Kalhoff, Hermann, additional, Kaulfersch, Wilhelm, additional, Kemen, Christoph, additional, Klocker, Nina, additional, Köster, Bernhard, additional, Kohlmaier, Benno, additional, Komini, Eleni, additional, Kramer, Lydia, additional, Neubert, Antje, additional, Ortner, Daniel, additional, Pescollderungg, Lydia, additional, Pfurtscheller, Klaus, additional, Reiter, Karl, additional, Ristic, Goran, additional, Rödl, Siegfried, additional, Sellner, Andrea, additional, Sonnleitner, Astrid, additional, Sperl, Matthias, additional, Stelzl, Wolfgang, additional, Till, Holger, additional, Trobisch, Andreas, additional, Vierzig, Anne, additional, Vogel, Ulrich, additional, Weingarten, Christina, additional, Welke, Stefanie, additional, Wimmer, Andreas, additional, Wintergerst, Uwe, additional, Wüller, Daniel, additional, Zaunschirm, Andrew, additional, Ziuraite, Ieva, additional, and Žukovskaja, Veslava, additional

Published
2018
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35. Does viral co-infection influence the severity of acute respiratory infection in children?

Author

Cebey López, Miriam, Herberg, Jethro, Pardo Seco, Jacobo José, Gómez Carballa, Alberto, Martinon-Torres, Nazareth, Salas Ellacuriaga, Antonio, Martinon-Torres, José María, Justicia Grande, Antonio, Rivero Calle, Irene, Sumner, Edward, Fink, Colin, Martinón Torres, Federico, GENDRES network, and Universidade de Santiago de Compostela. Departamento de Ciencias Forenses, Anatomía Patolóxica, Xinecoloxía e Obstetricia, e Pediatría

Subjects
Male, Pulmonology, Physiology, lcsh:Medicine, medicine.disease_cause, Pathology and Laboratory Medicine, Pneumococcal Vaccines, Families, 0302 clinical medicine, Medicine and Health Sciences, 030212 general & internal medicine, Respiratory system, lcsh:Science, Respiratory Tract Infections, Children, GENDRES network, Multidisciplinary, Respiratory distress, Respiratory tract infections, Coinfection, Respiration, Respiratory infection, Middle Aged, Hospitals, 3. Good health, Hospitalization, Chemistry, Phenotype, Infectious Diseases, Medical Microbiology, Superinfection, Child, Preschool, Viral Pathogens, Cohort, Acute Disease, Physical Sciences, Viruses, Female, Pathogens, Research Article, Chemical Elements, Adult, medicine.medical_specialty, General Science & Technology, Protective factor, Microbiology, 03 medical and health sciences, 030225 pediatrics, Internal medicine, Virology, MD Multidisciplinary, medicine, Humans, Microbial Pathogens, business.industry, lcsh:R, Infant, Newborn, Organisms, Infant, Biology and Life Sciences, medicine.disease, Oxygen, Health Care, Health Care Facilities, Age Groups, Co-Infections, Immunology, Respiratory Infections, People and Places, Population Groupings, lcsh:Q, business, Physiological Processes
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 This work was supported by the Spanish Government (Research Program Health Research Fund (FIS; PI10/00540) National Plan I + D + I and FEDER funds), by Regional Galician funds (Promotion of Research Project 10 PXIB 918 184PR) (FMT), by Ministerio de Ciencia e Innovación (SAF2011-26983), and by the Plan Galego IDT, Xunta de Galicia (EM 2012/045) (AS). A grant was received from the Sistema Universitario Gallego -Modalidad REDES (2014-PG139) from the Xunta de Galicia (to AS and FMT). MCL research activities have been supported by grants from Instituto de Investigación Sanitaria de Santiago de Compostela. FMT research activities have been supported by grants from Instituto Carlos III (Intensificación de la actividad investigadora). Investigators received funding from the European Union’s seventh Framework program under ECGA no. 279185 (EUCLIDS) during the production of this paper. JH was supported by the Imperial College Comprehensive Biomedical Research Centre and the Wellcome Trust Centre for Respiratory Infection at Imperial College (DMPED P26077 to JH). Micropathology Ltd. provided support in the form of salaries for authors ES and CF, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section SI

Published
2016

36. Identification and analysis of the impact of co-infections in pediatric patients hospitalized with lower tract acute respiratory infections

Author

Cebey López, Miriam, Martinón Torres, Federico, Salas Ellacuriaga, Antonio, Martinón Sánchez, José María, Universidade de Santiago de Compostela. Facultade de Medicina e Odontoloxía. Departamento de Pediatría, Martinón Torres, Federico (dir.), Salas Ellacuriaga, Antonio (dir.), and Martinón Sánchez, José María (dir.)

Subjects
IRAs, Red clínica GENDRES, Infecciones respiratorias, viruses, Investigación::32 Ciencias médicas::3210 Medicina preventiva [Materias], VRS
Abstract

Respiratory infections are a well-established child morbidity and mortality cause, which are estimated to cause 75% of all acute illness and are the leading cause of hospitalization for infants and young children worldwide. There are no methods of treatment or prevention through vaccination, except for specific agents (seasonal flu and H1N1) and in specific children with risk factors. However, the majority of respiratory infections occur in apparently healthy children without identifiable medical history, in which also the susceptibility, clinical course and prognosis vary widely even being affected by the same virus. Within this spectrum, respiratory syncytial virus (RSV) specifically is one of the paradigms of pediatric respiratory infection, frequency, morbidity and the absence of demonstrably effective preventive or therapeutic measures. While the clinical features of ARIs are easily recognized, the etiological agent responsible for disease is often not detected, as typically it is used direct immunofluorescence to detect RSV, influenza virus, parainfluenza virus and adenovirus. In this regard, the etiology of most lower respiratory tract infection is thought to be viral, but a virus is identified in approximately 40% of cases with this approach. Since the introduction of molecular diagnostic techniques, the identification of pathogens that escape from conventional modalities has increased. These molecular techniques frequently reveal the presence of more than one microorganism in the samples. The importance of these co-infections in the pathogenesis, severity or course of these respiratory infections is not well established. In the other hand, bacteremia risk is considered low in children with acute bronchiolitis and fever.

Published
2015

38. Differences between diabetic and non-diabetic patients with community-acquired pneumonia in primary care in Spain.

Author

Arias Fernández, Loreto, Pardo Seco, Jacobo, Cebey-López, Miriam, Gil Prieto, Ruth, Rivero-Calle, Irene, Martinon-Torres, Federico, Gil de Miguel, Ángel, Martinón-Torres, F., Vargas, D., Mascarós, E., Redondo, E., Díaz-Maroto, J. L., Linares-Rufo, M., Gil, A., Molina, J., Ocaña, D., Rivero-Calle, I., and NEUMOEXPERTOS group

Subjects
MEDICAL personnel, COMMUNITY-acquired pneumonia, PRIMARY care, PARKINSON'S disease, COMORBIDITY
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. [ABSTRACT FROM AUTHOR]

Published
2019
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39. Does Viral Co-Infection Influence the Severity of Acute Respiratory Infection in Children?

Author

Universidade de Santiago de Compostela. Departamento de Ciencias Forenses, Anatomía Patolóxica, Xinecoloxía e Obstetricia, e Pediatría, Cebey López, Miriam, Herberg, Jethro, Pardo Seco, Jacobo José, Gómez Carballa, Alberto, Martinon-Torres, Nazareth, Salas Ellacuriaga, Antonio, Martinon-Torres, José María, Justicia Grande, Antonio, Rivero Calle, Irene, Sumner, Edward, Fink, Colin, Martinón Torres, Federico, GENDRES network, Universidade de Santiago de Compostela. Departamento de Ciencias Forenses, Anatomía Patolóxica, Xinecoloxía e Obstetricia, e Pediatría, Cebey López, Miriam, Herberg, Jethro, Pardo Seco, Jacobo José, Gómez Carballa, Alberto, Martinon-Torres, Nazareth, Salas Ellacuriaga, Antonio, Martinon-Torres, José María, Justicia Grande, Antonio, Rivero Calle, Irene, Sumner, Edward, Fink, Colin, Martinón Torres, Federico, and GENDRES network

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

Published
2016

40. Bacteremia in Children Hospitalized with Respiratory Syncytial Virus Infection

Author

Universidade de Santiago de Compostela. Departamento de Ciencias Forenses, Anatomía Patolóxica, Xinecoloxía e Obstetricia, e Pediatría, Cebey López, Miriam, Pardo Seco, Jacobo José, Gómez Carballa, Alberto, Martinón Torres, Nazareth, Martinón-Torres, José María, Justicia Grande, Antonio, Rivero Calle, Irene, Pinnock, Ellie, Salas Ellacuriaga, Antonio, Fink, Colin, Martinón Torres, Federico, GENDRES network, Universidade de Santiago de Compostela. Departamento de Ciencias Forenses, Anatomía Patolóxica, Xinecoloxía e Obstetricia, e Pediatría, Cebey López, Miriam, Pardo Seco, Jacobo José, Gómez Carballa, Alberto, Martinón Torres, Nazareth, Martinón-Torres, José María, Justicia Grande, Antonio, Rivero Calle, Irene, Pinnock, Ellie, Salas Ellacuriaga, Antonio, Fink, Colin, Martinón Torres, Federico, and GENDRES network

Abstract

Background 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. Methods 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. Results 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). Conclusion Bacteremia is not frequent in infants hospitalized with RSV respiratory infection, however, it should be considered in the most severe cases

Published
2016

41. Development and Validation of a New Clinical Scale for Infants with Acute Respiratory Infection: The ReSVinet Scale

Author

Universidade de Santiago de Compostela. Departamento de Ciencias Forenses, Anatomía Patolóxica, Xinecoloxía e Obstetricia, e Pediatría, Justicia Grande, Antonio, Pardo Seco, Jacobo José, Cebey López, Miriam, Vilanova Trillo, Lucía, Gómez Carballa, Alberto, Rivero Calle, Irene, Puente-Puig, María, Curros-Novo, Carmen, Gómez Rial, Jose, Salas Ellacuriaga, Antonio, Martinon-Torres, José María, Redondo-Collazo, Lorenzo, Rodríguez-Tenreiro Sánchez, Carmen, Martinón Torres, Federico, Respiratory Syncytial Virus network (ReSVinet), Universidade de Santiago de Compostela. Departamento de Ciencias Forenses, Anatomía Patolóxica, Xinecoloxía e Obstetricia, e Pediatría, Justicia Grande, Antonio, Pardo Seco, Jacobo José, Cebey López, Miriam, Vilanova Trillo, Lucía, Gómez Carballa, Alberto, Rivero Calle, Irene, Puente-Puig, María, Curros-Novo, Carmen, Gómez Rial, Jose, Salas Ellacuriaga, Antonio, Martinon-Torres, José María, Redondo-Collazo, Lorenzo, Rodríguez-Tenreiro Sánchez, Carmen, Martinón Torres, Federico, and Respiratory Syncytial Virus network (ReSVinet)

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

Published
2016

42. Strong down-regulation of glycophorin genes: A host defense mechanism against rotavirus infection

Author

Salas, Antonio, primary, Marco-Puche, Guillermo, additional, Triviño, Juan Carlos, additional, Gómez-Carballa, Alberto, additional, Cebey-López, Miriam, additional, Rivero-Calle, Irene, additional, Vilanova-Trillo, Lucía, additional, Rodríguez-Tenreiro, Carmen, additional, Gómez-Rial, José, additional, and Martinón-Torres, Federico, additional

Published
2016
Full Text
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43. Role of Vitamin D in Hospitalized Children With Lower Tract Acute Respiratory Infections

Author

Cebey-López, Miriam, primary, Pardo-Seco, Jacobo, additional, Gómez-Carballa, Alberto, additional, Martinón-Torres, Nazareth, additional, Rivero-Calle, Irene, additional, Justicia, Antonio, additional, Redondo, Lorenzo, additional, Martinón-Sánchez, José María, additional, Martínez-Padilla, María del Carmen, additional, Giménez-Sánchez, Francisco, additional, Salas, Antonio, additional, and Martinón-Torres, Federico, additional

Published
2016
Full Text
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44. Identification and analysis of the impact of co-infections in pediatric patients hospitalized with lower tract acute respiratory infections

Author

Martinón Torres, Federico, Salas Ellacuriaga, Antonio, Martinón Sánchez, José María, Universidade de Santiago de Compostela. Facultade de Medicina e Odontoloxía. Departamento de Pediatría, Cebey López, Miriam, Martinón Torres, Federico, Salas Ellacuriaga, Antonio, Martinón Sánchez, José María, Universidade de Santiago de Compostela. Facultade de Medicina e Odontoloxía. Departamento de Pediatría, and Cebey López, Miriam

Abstract

Respiratory infections are a well-established child morbidity and mortality cause, which are estimated to cause 75% of all acute illness and are the leading cause of hospitalization for infants and young children worldwide. There are no methods of treatment or prevention through vaccination, except for specific agents (seasonal flu and H1N1) and in specific children with risk factors. However, the majority of respiratory infections occur in apparently healthy children without identifiable medical history, in which also the susceptibility, clinical course and prognosis vary widely even being affected by the same virus. Within this spectrum, respiratory syncytial virus (RSV) specifically is one of the paradigms of pediatric respiratory infection, frequency, morbidity and the absence of demonstrably effective preventive or therapeutic measures. While the clinical features of ARIs are easily recognized, the etiological agent responsible for disease is often not detected, as typically it is used direct immunofluorescence to detect RSV, influenza virus, parainfluenza virus and adenovirus. In this regard, the etiology of most lower respiratory tract infection is thought to be viral, but a virus is identified in approximately 40% of cases with this approach. Since the introduction of molecular diagnostic techniques, the identification of pathogens that escape from conventional modalities has increased. These molecular techniques frequently reveal the presence of more than one microorganism in the samples. The importance of these co-infections in the pathogenesis, severity or course of these respiratory infections is not well established. In the other hand, bacteremia risk is considered low in children with acute bronchiolitis and fever.

Published
2015

45. Development and Validation of a New Clinical Scale for Infants with Acute Respiratory Infection: The ReSVinet Scale

Author

Justicia Grande, Antonio, Pardo Seco, Jacobo José, Cebey López, Miriam, Vilanova Trillo, Lucía, Gómez Carballa, Alberto, Rivero Calle, Irene, Puente-Puig, María, Curros-Novo, Carmen, Gómez Rial, Jose, Salas Ellacuriaga, Antonio, Martinon-Torres, José María, Redondo-Collazo, Lorenzo, Rodríguez-Tenreiro Sánchez, Carmen, Martinón Torres, Federico, Respiratory Syncytial Virus network (ReSVinet), and Universidade de Santiago de Compostela. Departamento de Ciencias Forenses, Anatomía Patolóxica, Xinecoloxía e Obstetricia, e Pediatría

Subjects
Parents, Pediatrics, Pulmonology, Medical Doctors, Health Care Providers, lcsh:Medicine, Cohort Studies, Families, 0302 clinical medicine, Surveys and Questionnaires, Outpatients, Medicine and Health Sciences, Medicine, 030212 general & internal medicine, lcsh:Science, Children, Respiratory Tract Infections, Multidisciplinary, Respiratory tract infections, Medical record, Respiratory infection, 3. Good health, Professions, Chemistry, Physical Sciences, Acute Disease, Bronchiolitis, Infants, Research Article, Chemical Elements, Cohort study, medicine.medical_specialty, Patients, Scale (ratio), Pediatric Pulmonology, 03 medical and health sciences, Cronbach's alpha, Physicians, 030225 pediatrics, Humans, business.industry, lcsh:R, Infant, Reproducibility of Results, medicine.disease, Health Care, Oxygen, Age Groups, People and Places, Respiratory Infections, lcsh:Q, Population Groupings, business, Kappa
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 This work was supported by the Spanish Government (Research Program Health Research Fund – [http://www.gendres.org] (FIS; PI10/00540 y PI13/02382) National Plan I + D + I and FEDER funds) and Regional Galician funds (Promotion of Research Project 10 PXIB 918 184 PR) (FMT), and Ministerio de Ciencia e Innovación (SAF2011-26983) and the Plan Galego IDT, Xunta de Galicia (EM 2012/045) (AS). MC’s research activities have been supported by grants from Instituto de Investigación Sanitaria de Santiago de Compostela. FMT’s research activities have been supported by grants from Instituto Carlos III (Intensificación de la actividad investigadora- ISCIII/INT14/00245/ Cofinanciado FEDER), Spanish National Plan I + D + i and FEDER funds. Investigators received funding from the European Union’s Seventh Framework Program under ECGA no. 279185 (EUCLIDS – [http://www.euclids-project.eu]) during the production of this paper. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript SI

Published
2016

46. Bacteremia in Children Hospitalized with Respiratory Syncytial Virus Infection

Author

Cebey López, Miriam, Pardo Seco, Jacobo José, Gómez Carballa, Alberto, Martinón Torres, Nazareth, Martinón-Torres, José María, Justicia Grande, Antonio, Rivero Calle, Irene, Pinnock, Ellie, Salas Ellacuriaga, Antonio, Fink, Colin, Martinón Torres, Federico, GENDRES network, and Universidade de Santiago de Compostela. Departamento de Ciencias Forenses, Anatomía Patolóxica, Xinecoloxía e Obstetricia, e Pediatría

Subjects
Male, Bacterial Diseases, Pulmonology, Physiology, lcsh:Medicine, Fevers, Bacteremia, Artificial Gene Amplification and Extension, Pathology and Laboratory Medicine, medicine.disease_cause, Severity of Illness Index, Polymerase Chain Reaction, Haemophilus influenzae, Families, 0302 clinical medicine, Antibiotics, Medicine and Health Sciences, Prospective Studies, 030212 general & internal medicine, lcsh:Science, Children, Multidisciplinary, Coinfection, Antimicrobials, Drugs, Respiratory infection, Hematology, Anti-Bacterial Agents, Body Fluids, 3. Good health, Hospitalization, Infectious Diseases, Blood, Child, Preschool, Superinfection, Acute Disease, Bronchiolitis, Female, Anatomy, Research Article, medicine.medical_specialty, Respiratory Syncytial Virus Infections, Gram-Positive Bacteria, Research and Analysis Methods, Microbiology, 03 medical and health sciences, Signs and Symptoms, Microbial Control, 030225 pediatrics, Internal medicine, Gram-Negative Bacteria, Streptococcus pneumoniae, Severity of illness, medicine, Humans, Molecular Biology Techniques, Molecular Biology, Gram-Positive Bacterial Infections, Pharmacology, business.industry, lcsh:R, Infant, Biology and Life Sciences, medicine.disease, Age Groups, Respiratory Syncytial Virus, Human, Respiratory Infections, People and Places, Immunology, lcsh:Q, Population Groupings, Gram-Negative Bacterial Infections, business
Abstract

Background 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. Methods 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. Results 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). Conclusion Bacteremia is not frequent in infants hospitalized with RSV respiratory infection, however, it should be considered in the most severe cases This work was supported by the Spanish Government (Research Program Health Research Fund (FIS; PI10/00540 y PI13/02382) National Plan I + D + I and FEDER funds) and Regional Galician funds (Promotion of Research Project 10 PXIB 918 184 PR) (FMT), and Ministerio de Ciencia e Innovación (SAF2011-26983) and the Plan Galego IDT, Xunta de Galicia (EM 2012/045) (AS). MC’s research activities had been supported by grants from Instituto de Investigación Sanitaria de Santiago de Compostela. FMT’s research activities have been supported by grants from Instituto Carlos III (Intensificación de la actividad investigadora). Investigators received funding from the European Union’s Seventh Framework Program under ECGA no. 279185 (EUCLIDS) during the production of this paper SI

Published
2016

48. Indian Signatures in the Westernmost Edge of the European Romani Diaspora: New Insight from Mitogenomes

Author

Universidade de Santiago de Compostela. Departamento de Ciencias Forenses, Anatomía Patolóxica, Xinecoloxía e Obstetricia, e Pediatría, Gómez Carballa, Alberto, Pardo Seco, Jacobo José, Fachal Vilar, Laura, Vega Gliemmo, Ana Paula, Cebey López, Miriam, Martinón Torres, Nazareth, Martinón Torres, Federico, Salas Ellacuriaga, Antonio, Universidade de Santiago de Compostela. Departamento de Ciencias Forenses, Anatomía Patolóxica, Xinecoloxía e Obstetricia, e Pediatría, Gómez Carballa, Alberto, Pardo Seco, Jacobo José, Fachal Vilar, Laura, Vega Gliemmo, Ana Paula, Cebey López, Miriam, Martinón Torres, Nazareth, Martinón Torres, Federico, and Salas Ellacuriaga, Antonio

Abstract

In agreement with historical documentation, several genetic studies have revealed ancestral links between the European Romani and India. The entire mitochondrial DNA (mtDNA) of 27 Spanish Romani was sequenced in order to shed further light on the origins of this population. The data were analyzed together with a large published dataset (mainly hypervariable region I [HVS-I] haplotypes) of Romani (N = 1,353) and non-Romani worldwide populations (N.150,000). Analysis of mitogenomes allowed the characterization of various Romani-specific clades. M5a1b1a1 is the most distinctive European Romani haplogroup; it is present in all Romani groups at variable frequencies (with only sporadic findings in nonRomani) and represents 18% of their mtDNA pool. Its phylogeographic features indicate that M5a1b1a1 originated 1.5 thousand years ago (kya; 95% CI: 1.3–1.8) in a proto-Romani population living in Northwest India. U3 represents the most characteristic Romani haplogroup of European/Near Eastern origin (12.4%); it appears at dissimilar frequencies across the continent (Iberia: ,31%; Eastern/Central Europe: ,13%). All U3 mitogenomes of our Iberian Romani sample fall within a new sub-clade, U3b1c, which can be dated to 0.5 kya (95% CI: 0.3–0.7); therefore, signaling a lower bound for the founder event that followed admixture in Europe/Near East. Other minor European/Near Eastern haplogroups (e.g. H24, H88a) were also assimilated into the Romani by introgression with neighboring populations during their diaspora into Europe; yet some show a differentiation from the phylogenetically closest non-Romani counterpart. The phylogeny of Romani mitogenomes shows clear signatures of low effective population sizes and founder effects. Overall, these results are in good agreement with historical documentation, suggesting that cultural identity and relative isolation have allowed the Romani to preserve a distinctive mtDNA heritage, with some features linking them unequivocally to their ancestr

Published
2013

49. Does Viral Co-Infection Influence the Severity of Acute Respiratory Infection in Children?

Author

Cebey-López, Miriam, Herberg, Jethro, Pardo-Seco, Jacobo, Gómez-Carballa, Alberto, Martinón-Torres, Nazareth, Salas, Antonio, Martinón-Sánchez, José María, Justicia, Antonio, Rivero-Calle, Irene, Sumner, Edward, Fink, Colin, Martinón-Torres, Federico, and null, null

Subjects
*MIXED infections, *RESPIRATORY infections in children, *VIRUS diseases, *PHENOTYPES, *HOSPITAL care of children, *HEALTH outcome assessment, *DIAGNOSIS
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. [ABSTRACT FROM AUTHOR]

Published
2016
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50. Viral Co-Infections in Pediatric Patients Hospitalized with Lower Tract Acute Respiratory Infections.

Author

Cebey-López, Miriam, Herberg, Jethro, Pardo-Seco, Jacobo, Gómez-Carballa, Alberto, Martinón-Torres, Nazareth, Salas, Antonio, Martinón-Sánchez, José María, Gormley, Stuart, Sumner, Edward, Fink, Colin, Martinón-Torres, Federico, and null, null

Subjects
*VIRUS diseases, *PEDIATRICS, *HOSPITAL admission & discharge, *RESPIRATORY infections, *PATIENTS
Abstract

Background: 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. Methods: 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. Results: 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). Conclusion: 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. [ABSTRACT FROM AUTHOR]

Published
2015
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