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1. Diagnosis of Multisystem Inflammatory Syndrome in Children by a Whole-Blood Transcriptional Signature

Author: Jackson, Heather R, Miglietta, Luca, Habgood-Coote, Dominic, D'Souza, Giselle, Shah, Priyen, Nichols, Samuel, Vito, Ortensia, Powell, Oliver, Davidson, Maisey Salina, Shimizu, Chisato, Agyeman, Philipp KA, Beudeker, Coco R, Brengel-Pesce, Karen, Carrol, Enitan D, Carter, Michael J, De, Tisham, Eleftheriou, Irini, Emonts, Marieke, Epalza, Cristina, Georgiou, Pantelis, De Groot, Ronald, Fidler, Katy, Fink, Colin, van Keulen, Daniëlle, Kuijpers, Taco, Moll, Henriette, Papatheodorou, Irene, Paulus, Stephane, Pokorn, Marko, Pollard, Andrew J, Rivero-Calle, Irene, Rojo, Pablo, Secka, Fatou, Schlapbach, Luregn J, Tremoulet, Adriana H, Tsolia, Maria, Usuf, Effua, Van Der Flier, Michiel, Von Both, Ulrich, Vermont, Clementien, Yeung, Shunmay, Zavadska, Dace, Zenz, Werner, Coin, Lachlan JM, Cunnington, Aubrey, Burns, Jane C, Wright, Victoria, Martinon-Torres, Federico, Herberg, Jethro A, Rodriguez-Manzano, Jesus, Kaforou, Myrsini, and Levin, Michael
Subjects: Paediatrics, Medical Microbiology, Biomedical and Clinical Sciences, Pediatric, Genetics, Infectious Diseases, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, Child, Humans, COVID-19, Systemic Inflammatory Response Syndrome, Hospitals, Mucocutaneous Lymph Node Syndrome, COVID-19 Testing, MIS-C, diagnostic signature, host diagnostics, host response, pediatric infectious diseases, rapid diagnostics, transcriptomics, Medical microbiology
Abstract: BackgroundTo identify a diagnostic blood transcriptomic signature that distinguishes multisystem inflammatory syndrome in children (MIS-C) from Kawasaki disease (KD), bacterial infections, and viral infections.MethodsChildren presenting with MIS-C to participating hospitals in the United Kingdom and the European Union between April 2020 and April 2021 were prospectively recruited. Whole-blood RNA Sequencing was performed, contrasting the transcriptomes of children with MIS-C (n = 38) to those from children with KD (n = 136), definite bacterial (DB; n = 188) and viral infections (DV; n = 138). Genes significantly differentially expressed (SDE) between MIS-C and comparator groups were identified. Feature selection was used to identify genes that optimally distinguish MIS-C from other diseases, which were subsequently translated into RT-qPCR assays and evaluated in an independent validation set comprising MIS-C (n = 37), KD (n = 19), DB (n = 56), DV (n = 43), and COVID-19 (n = 39).ResultsIn the discovery set, 5696 genes were SDE between MIS-C and combined comparator disease groups. Five genes were identified as potential MIS-C diagnostic biomarkers (HSPBAP1, VPS37C, TGFB1, MX2, and TRBV11-2), achieving an AUC of 96.8% (95% CI: 94.6%-98.9%) in the discovery set, and were translated into RT-qPCR assays. The RT-qPCR 5-gene signature achieved an AUC of 93.2% (95% CI: 88.3%-97.7%) in the independent validation set when distinguishing MIS-C from KD, DB, and DV.ConclusionsMIS-C can be distinguished from KD, DB, and DV groups using a 5-gene blood RNA expression signature. The small number of genes in the signature and good performance in both discovery and validation sets should enable the development of a diagnostic test for MIS-C.
Published: 2023

2. Emergency medical services utilisation among febrile children attending emergency departments across Europe: an observational multicentre study

Author: Tan, Chantal D., Vermont, Clementien L., Zachariasse, Joany M., von Both, Ulrich, Eleftheriou, Irini, Emonts, Marieke, van der Flier, Michiel, Herberg, Jethro, Kohlmaier, Benno, Levin, Michael, Lim, Emma, Maconochie, Ian K., Martinon-Torres, Federico, Nijman, Ruud G., Pokorn, Marko, Rivero-Calle, Irene, Tsolia, Maria, Zenz, Werner, Zavadska, Dace, Moll, Henriëtte A., and Carrol, Enitan D.
Published: 2023
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3. 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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4. 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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5. Diagnosis of childhood febrile illness using a multi-class blood RNA molecular signature

Author: Habgood-Coote, Dominic, Wilson, Clare, Shimizu, Chisato, Barendregt, Anouk M., Philipsen, Ria, Galassini, Rachel, Calle, Irene Rivero, Workman, Lesley, Agyeman, Philipp K.A., Ferwerda, Gerben, Anderson, Suzanne T., van den Berg, J. Merlijn, Emonts, Marieke, Carrol, Enitan D., Fink, Colin G., de Groot, Ronald, Hibberd, Martin L., Kanegaye, John, Nicol, Mark P., Paulus, Stéphane, Pollard, Andrew J., Salas, Antonio, Secka, Fatou, Schlapbach, Luregn J., Tremoulet, Adriana H., Walther, Michael, Zenz, Werner, Van der Flier, Michiel, Zar, Heather J., Kuijpers, Taco, Burns, Jane C., Martinón-Torres, Federico, Wright, Victoria J., Coin, Lachlan J.M., Cunnington, Aubrey J., Herberg, Jethro A., Levin, Michael, and Kaforou, Myrsini
Published: 2023
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6. 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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7. Group A streptococcal disease in paediatric inpatients: a European perspective

Author: Boeddha, Navin P., Atkins, Lucy, de Groot, Ronald, Driessen, Gertjan, Hazelzet, Jan, Zenz, Werner, Carrol, Enitan D., Anderson, Suzanne T., Martinon-Torres, Federico, Agyeman, Philipp K. A., Galassini, Rachel, Herberg, Jethro, Levin, Michael, Schlapbach, Luregn J., and Emonts, Marieke
Published: 2023
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8. 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, and Emonts, Marieke
Published: 2023
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9. Correction to: Guideline adherence in febrile children below 3 months visiting European Emergency Departments: an observational multicenter study

Author: Tan, Chantal D., van der Walle, Eline E. P. L., Vermont, Clementien L., von Both, Ulrich, Carrol, Enitan D., Eleftheriou, Irini, Emonts, Marieke, van der Flier, Michiel, de Groot, Ronald, Herberg, Jethro, Kohlmaier, Benno, Levin, Michael, Lim, Emma, Maconochie, Ian K., Martinon-Torres, Federico, Nijman, Ruud G., Pokorn, Marko, Rivero-Calle, Irene, Tsolia, Maria, Yeung, Shunmay, Zenz, Werner, Zavadska, Dace, and Moll, Henriëtte A.
Published: 2022
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10. Guideline adherence in febrile children below 3 months visiting European Emergency Departments: an observational multicenter study

Author: Tan, Chantal D., van der Walle, Eline E. P. L., Vermont, Clementien L., von Both, Ulrich, Carrol, Enitan D., Eleftheriou, Irini, Emonts, Marieke, van der Flier, Michiel, de Groot, Ronald, Herberg, Jethro, Kohlmaier, Benno, Levin, Michael, Lim, Emma, Maconochie, Ian K., Martinon-Torres, Federico, Nijman, Ruud G., Pokorn, Marko, Rivero-Calle, Irene, Tsolia, Maria, Yeung, Shunmay, Zenz, Werner, Zavadska, Dace, and Moll, Henriëtte A.
Published: 2022
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11. 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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12. Biomarkers for the Discrimination of Acute Kawasaki Disease From Infections in Childhood

Author: Zandstra, Judith, van de Geer, Annemarie, Tanck, Michael WT, van Stijn-Bringas Dimitriades, Diana, Aarts, Cathelijn EM, Dietz, Sanne M, van Bruggen, Robin, Schweintzger, Nina A, Zenz, Werner, Emonts, Marieke, Zavadska, Dace, Pokorn, Marko, Usuf, Effua, Moll, Henriette A, Schlapbach, Luregn J, Carrol, Enitan D, Paulus, Stephane, Tsolia, Maria, Fink, Colin, Yeung, Shunmay, Shimizu, Chisato, Tremoulet, Adriana, Galassini, Rachel, Wright, Victoria J, Martinón-Torres, Federico, Herberg, Jethro, Burns, Jane, Levin, Michael, Kuijpers, Taco W, and Consortium, PERFORM Consortium and UK Kawasaki Disease Genetics Study Network EUCLIDS
Subjects: Biomedical and Clinical Sciences, Clinical Sciences, Pediatric, Infectious Diseases, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, Infection, Inflammatory and immune system, Good Health and Well Being, kawasaki disease, infectious disease, vasculitis, coronary aneurysm, biomarker, bacterial infection, viral infection, EUCLIDS Consortium, PERFORM Consortium and UK Kawasaki Disease Genetics Study Network, Paediatrics and Reproductive Medicine, Other Medical and Health Sciences, Paediatrics
Abstract: Background: Kawasaki disease (KD) is a vasculitis of early childhood mimicking several infectious diseases. Differentiation between KD and infectious diseases is essential as KD's most important complication-the development of coronary artery aneurysms (CAA)-can be largely avoided by timely treatment with intravenous immunoglobulins (IVIG). Currently, KD diagnosis is only based on clinical criteria. The aim of this study was to evaluate whether routine C-reactive protein (CRP) and additional inflammatory parameters myeloid-related protein 8/14 (MRP8/14 or S100A8/9) and human neutrophil-derived elastase (HNE) could distinguish KD from infectious diseases. Methods and Results: The cross-sectional study included KD patients and children with proven infections as well as febrile controls. Patients were recruited between July 2006 and December 2018 in Europe and USA. MRP8/14, CRP, and HNE were assessed for their discriminatory ability by multiple logistic regression analysis with backward selection and receiver operator characteristic (ROC) curves. In the discovery cohort, the combination of MRP8/14+CRP discriminated KD patients (n = 48) from patients with infection (n = 105), with area under the ROC curve (AUC) of 0.88. The HNE values did not improve discrimination. The first validation cohort confirmed the predictive value of MRP8/14+CRP to discriminate acute KD patients (n = 26) from those with infections (n = 150), with an AUC of 0.78. The second validation cohort of acute KD patients (n = 25) and febrile controls (n = 50) showed an AUC of 0.72, which improved to 0.84 when HNE was included. Conclusion: When used in combination, the plasma markers MRP8/14, CRP, and HNE may assist in the discrimination of KD from both proven and suspected infection.
Published: 2020

13. Febrile children with comorbidities at the emergency department — a multicentre observational study

Author: Borensztajn, Dorine M., Hagedoorn, Nienke N., Carrol, Enitan D., von Both, Ulrich, Emonts, Marieke, van der Flier, Michiel, de Groot, Ronald, Herberg, Jethro, Kohlmaier, Benno, Levin, Michael, Lim, Emma, Maconochie, Ian K., Martinon-Torres, Federico, Nijman, Ruud G., Pokorn, Marko, Rivero-Calle, Irene, Tsolia, Maria, van der Velden, Fabian J. S., Vermont, Clementien, Zavadska, Dace, Zenz, Werner, Zachariasse, Joany M., and Moll, Henriette A.
Published: 2022
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14. Correction to: 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, and Emonts, Marieke
Published: 2023
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15. Hemostasis Proteins in Invasive Meningococcal and Nonmeningococcal Infections: A Prospective Multicenter Study

Author: Hagedoorn, Nienke N., Boeddha, Navin P., Kohlfuerst, Daniela S., Anderson, Suzanne, Carrol, Enitan D., Agapow, Paul, van der Flier, Michiel, Hazelzet, Jan, Herberg, Jethro, Kuijpers, Taco, Levin, Michael, Martinon-Torres, Federico, van Rijswijk, Angelique, Schlapbach, Luregn J., Vermont, Clementien, Zenz, Werner, Dik, Willem A., Driessen, Gertjan, and Emonts, Marieke
Published: 2022
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16. Which low urgent triaged febrile children are suitable for a fast track? An observational European study

Author: Tan, Chantal D., Vermont, Clementien L., Zachariasse, Joany M., von Both, Ulrich, Carrol, Enitan D., Eleftheriou, Irini, Emonts, Marieke, van der Flier, Michiel, Herberg, Jethro, Kohlmaier, Benno, Levin, Michael, Lim, Emma, Maconochie, Ian K., Martinon-Torres, Federico, Nijman, Ruud G., Pokorn, Marko, Rivero-Calle, Irene, Rudzāte, Aleksandra, Tsolia, Maria, Zenz, Werner, Zavadska, Dace, Moll, Henriette A., Tan, Chantal D., Vermont, Clementien L., Zachariasse, Joany M., von Both, Ulrich, Carrol, Enitan D., Eleftheriou, Irini, Emonts, Marieke, van der Flier, Michiel, Herberg, Jethro, Kohlmaier, Benno, Levin, Michael, Lim, Emma, Maconochie, Ian K., Martinon-Torres, Federico, Nijman, Ruud G., Pokorn, Marko, Rivero-Calle, Irene, Rudzāte, Aleksandra, Tsolia, Maria, Zenz, Werner, Zavadska, Dace, and Moll, Henriette A.
Abstract: Background:The number of paediatric patients visiting the ED with non-urgent problems is increasing, leading to poor patient flow and ED crowding. Fast track aims to improve the efficiency of evaluation and discharge of low acuity patients. We aimed to identify which febrile children are suitable for a fast track based on presenting symptoms and management. Methods:This study is part of the Management and Outcome of Fever in children in Europe study, which is an observational study including routine data of febrile children <18 years attending 12 European EDs. We included febrile, low urgent children (those assigned a triage acuity of either’standard’ or’non-urgent’ using the Manchester Triage System) and defined children as suitable for fast track when they have minimal resource use and are discharged home. Presenting symptoms consisted of neurological (n=237), respiratory (n=8476), gastrointestinal (n=1953) and others (n=3473, reference group). Multivariable logistic regression analyses regarding presenting symptoms and management (laboratory blood testing, imaging and admission) were performed with adjustment for covariates: patient characteristics, referral status, previous medical care, previous antibiotic use, visiting hours and ED setting. Results:We included 14 139 children with a median age of 2.7 years (IQR 1.3–5.2). The majority had respiratory symptoms (60%), viral infections (50%) and consisted of self-referrals (69%). The neurological group received imaging more often (adjusted OR (aOR) 1.8, 95% CI 1.1 to 2.9) and were admitted more frequently (aOR 1.9, 95% CI 1.4 to 2.7). The respiratory group had fewer laboratory blood tests performed (aOR 0.6, 95% CI 0.5 to 0.7), were less frequently admitted (aOR 0.6, 95% CI 0.5 to 0.7), but received imaging more often (aOR 1.8, 95% CI 1.6 to 2.0). Lastly, the gastrointestinal group had more laboratory blood tests performed (aOR 1.2. 95% CI 1.1 to 1.4) a
Published: 2024

17. Which low urgent triaged febrile children are suitable for a fast track? An observational European study

Author: Infectieziekten patientenzorg, Child Health, Infection & Immunity, Tan, Chantal D., Vermont, Clementien L., Zachariasse, Joany M., Von Both, Ulrich, Carrol, Enitan D., Eleftheriou, Irini, Emonts, Marieke, Van Der Flier, Michiel, Herberg, Jethro, Kohlmaier, Benno, Levin, Michael, Lim, Emma, Maconochie, Ian K., Martinon-Torres, Federico, Nijman, Ruud G., Pokorn, Marko, Rivero-Calle, Irene, RudzÄa Te, Aleksandra, Tsolia, Maria, Zenz, Werner, Zavadska, Dace, Moll, Henriette A., Infectieziekten patientenzorg, Child Health, Infection & Immunity, Tan, Chantal D., Vermont, Clementien L., Zachariasse, Joany M., Von Both, Ulrich, Carrol, Enitan D., Eleftheriou, Irini, Emonts, Marieke, Van Der Flier, Michiel, Herberg, Jethro, Kohlmaier, Benno, Levin, Michael, Lim, Emma, Maconochie, Ian K., Martinon-Torres, Federico, Nijman, Ruud G., Pokorn, Marko, Rivero-Calle, Irene, RudzÄa Te, Aleksandra, Tsolia, Maria, Zenz, Werner, Zavadska, Dace, and Moll, Henriette A.
Published: 2024

18. Correction to: Group A streptococcal disease in paediatric inpatients: a European perspective

Author: Boeddha, Navin P., Atkins, Lucy, de Groot, Ronald, Driessen, Gertjan, Hazelzet, Jan, Zenz, Werner, Carrol, Enitan D., Anderson, Suzanne T., Martinon-Torres, Federico, Agyeman, Philipp K. A., Galassini, Rachel, Herberg, Jethro, Levin, Michael, Schlapbach, Luregn J., and Emonts, Marieke
Published: 2023
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19. Which low urgent triaged febrile children are suitable for a fast track? An observational European study

Author: Tan, Chantal D, primary, Vermont, Clementien L, additional, Zachariasse, Joany M, additional, von Both, Ulrich, additional, Carrol, Enitan D, additional, Eleftheriou, Irini, additional, Emonts, Marieke, additional, van der Flier, Michiel, additional, Herberg, Jethro, additional, Kohlmaier, Benno, additional, Levin, Michael, additional, Lim, Emma, additional, Maconochie, Ian K, additional, Martinon-Torres, Federico, additional, Nijman, Ruud G, additional, Pokorn, Marko, additional, Rivero-Calle, Irene, additional, Rudzāte, Aleksandra, additional, Tsolia, Maria, additional, Zenz, Werner, additional, Zavadska, Dace, additional, and Moll, Henriette A, additional
Published: 2024
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20. Risk Factors for Complicated Lymphadenitis Caused by Nontuberculous Mycobacteria in Children

Author: Kuntz, Martin, Kohlfurst, Daniela S., Feiterna-Sperling, Cornelia, Kruger, Renate, Baumann, Ulrich, Buchtala, Laura, Elling, Roland, Grote, Veit, Hubner, Johannes, Hufnagel, Markus, Kaiser-Labusch, Petra, Liese, Johannes, Otto, Eva-Maria, Rose, Markus A., Schneider, Christian, Schuster, Volker, Seidl, Maximilian, Sommerburg, Olaf, Vogel, Markus, von Bernuth, Horst, Weiss, Michael, Zimmermann, Theodor, Nieters, Alexandra, Zenz, Werner, and Henneke, Philipp
Subjects: Prevalence studies (Epidemiology), Pediatric communicable diseases -- Risk factors, Lifestyles -- Health aspects, Lymphadenitis -- Risk factors, Mycobacterium infections -- Risk factors, Microbiology, Lymphatic diseases, Infection, Diseases, Health
Abstract: Nontuberculous mycobacteria (NTM) are common in the environment. NTM frequently are found in soil and are the most common bacteria on showerhead surfaces (2,2). Although many children likely have daily [...]
Published: 2020
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21. Rapid Viral Testing and Antibiotic Prescription in Febrile Children With Respiratory Symptoms Visiting Emergency Departments in Europe

Author: Tan, Chantal D., Hagedoorn, Nienke N., Dewez, Juan E., Borensztajn, Dorine M., von Both, Ulrich, Carrol, Enitan D., Emonts, Marieke, van der Flier, Michiel, de Groot, Ronald, Herberg, Jethro, Kohlmaier, Benno, Levin, Michael, Lim, Emma, Maconochie, Ian K., Martinon-Torres, Federico, Nijman, Ruud G., Pokorn, Marko, Rivero-Calle, Irene, Strle, Franc, Tsolia, Maria, Vermont, Clementien L., Yeung, Shunmay, Zachariasse, Joany M., Zenz, Werner, Zavadska, Dace, and Moll, Henriette A.
Published: 2022
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22. Detectable A Disintegrin and Metalloproteinase With Thrombospondin Motifs-1 in Serum Is Associated With Adverse Outcome in Pediatric Sepsis

Author: Boeddha, Navin P., Driessen, Gertjan J., Hagedoorn, Nienke N., Kohlfuerst, Daniela S., Hoggart, Clive J., van Rijswijk, Angelique L., Ekinci, Ebru, Priem, Debby, Schlapbach, Luregn J., Herberg, Jethro A., de Groot, Ronald, Anderson, Suzanne T., Fink, Colin G., Carrol, Enitan D., van der Flier, Michiel, Martinón-Torres, Federico, Levin, Michael, Leebeek, Frank W., Zenz, Werner, de Maat, Moniek P. M., Hazelzet, Jan A., Emonts, Marieke, and Dik, Willem A.
Published: 2021
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23. External validation of a multivariable prediction model for identification of pneumonia and other serious bacterial infections in febrile immunocompromised children

Author: Martin, Alexander James, primary, van der Velden, Fabian Johannes Stanislaus, additional, von Both, Ulrich, additional, Tsolia, Maria N, additional, Zenz, Werner, additional, Sagmeister, Manfred, additional, Vermont, Clementien, additional, de Vries, Gabriella, additional, Kolberg, Laura, additional, Lim, Emma, additional, Pokorn, Marko, additional, Zavadska, Dace, additional, Martinón-Torres, Federico, additional, Rivero-Calle, Irene, additional, Hagedoorn, Nienke N, additional, Usuf, Effua, additional, Schlapbach, Luregn, additional, Kuijpers, Taco W, additional, Pollard, Andrew J, additional, Yeung, Shunmay, additional, Fink, Colin, additional, Voice, Marie, additional, Carrol, Enitan, additional, Agyeman, Philipp K A, additional, Khanijau, Aakash, additional, Paulus, Stephane, additional, De, Tisham, additional, Herberg, Jethro Adam, additional, Levin, Michael, additional, van der Flier, Michiel, additional, de Groot, Ronald, additional, Nijman, Ruud, additional, and Emonts, Marieke, additional
Published: 2023
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24. 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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25. 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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26. Variation in CFHR3 determines susceptibility to meningococcal disease by controlling factor H concentrations

Author: Kumar, Vikrant, Pouw, Richard B, Autio, Matias I, Sagmeister, Manfred G, Phua, Zai Yang, Borghini, Lisa, Wright, Victoria J, Hoggart, Clive, Pan, Bangfen, Tan, Antson Kiat Yee, Binder, Alexander, Brouwer, Mieke C, Pinnock, Ellie, De Groot, Ronald, Hazelzet, Jan, Emonts, Marieke, Van Der Flier, Michiel, Reiter, Karl, Nöthen, Markus M, Hoffmann, Per, EUCLIDS consortium, Schlapbach, Luregn J, Bellos, Evangelos, Anderson, Suzanne, Secka, Fatou, Martinón-Torres, Federico, Salas, Antonio, Fink, Colin, Carrol, Enitan D, Pollard, Andrew J, Coin, Lachlan J, Zenz, Werner, Wouters, Diana, Ang, Lay Teng, Hibberd, Martin L, Levin, Michael, Kuijpers, Taco W, Davila, Sonia, consortium, EUCLIDS, Pediatrics, Paediatric Infectious Diseases / Rheumatology / Immunology, Landsteiner Laboratory, and ARD - Amsterdam Reproduction and Development
Subjects: CFHR3, Genotype, Meningococcal disease, infectious disease, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Complement, in-depth sequencing, Blood Proteins, Complement System Proteins, Neisseria meningitidis, factor H, QR, Meningococcal Infections, Factor H-related protein, genotyping, Complement Factor H, Genetics, Humans, CFH, Genetic Predisposition to Disease, Genetics (clinical), RC
Abstract: Neisseria meningitidis protects itself from complement-mediated killing by binding complement factor H (FH). Previous studies associated susceptibility to meningococcal disease (MD) with variation in CFH, but the causal variants and underlying mechanism remained unknown. Here we attempted to define the association more accurately by sequencing the CFH-CFHR locus and imputing missing genotypes in previously obtained GWAS datasets of MD-affected individuals of European ancestry and matched controls. We identified a CFHR3 SNP that provides protection from MD (rs75703017, p value = 1.1 × 10−16) by decreasing the concentration of FH in the blood (p value = 1.4 × 10−11). We subsequently used dual-luciferase studies and CRISPR gene editing to establish that deletion of rs75703017 increased FH expression in hepatocyte by preventing promotor inhibition. Our data suggest that reduced concentrations of FH in the blood confer protection from MD; with reduced access to FH, N. meningitidis is less able to shield itself from complement-mediated killing.
Published: 2022

27. External validation of a multivariable prediction model for identification of pneumonia and other serious bacterial infections in febrile immunocompromised children.

Author: Martin, Alexander James, Stanislaus van der Velden, Fabian Johannes, von Both, Ulrich, Tsolia, Maria N., Zenz, Werner, Sagmeister, Manfred, Vermont, Clementien, de Vries, Gabriella, Kolberg, Laura, Lim, Emma, Pokorn, Marko, Zavadska, Dace, Torres, Federico Martinón, Rivero Calle, Irene, Hagedoorn, Nienke N., Usuf, Effua, Schlapbach, Luregn, Kuijpers, Taco W., Pollard, Andrew J., and Shunmay Yeung
Subjects: FEBRILE neutropenia, BACTERIAL diseases, URINARY tract infections, IMMUNOCOMPROMISED patients, PREDICTION models, PNEUMONIA, RESPIRATORY infections
Published: 2024
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28. Are children with prolonged fever at a higher risk for serious illness? A prospective observational study

Author: Nijman, Ruud G, primary, Tan, Chantal D, additional, Hagedoorn, Nienke N, additional, Nieboer, Daan, additional, Herberg, Jethro Adam, additional, Balode, Anda, additional, von Both, Ulrich, additional, Carrol, Enitan D, additional, Eleftheriou, Irini, additional, Emonts, Marieke, additional, van der Flier, Michiel, additional, de Groot, Ronald, additional, Kohlmaier, Benno, additional, Lim, Emma, additional, Martinón-Torres, Federico, additional, Pokorn, Marko, additional, Strle, Franc, additional, Tsolia, Maria, additional, Yeung, Shunmay, additional, Zachariasse, Joany M, additional, Zavadska, Dace, additional, Zenz, Werner, additional, Levin, Michael, additional, Vermont, Clementien L, additional, Moll, Henriette A, additional, and Maconochie, Ian K, additional
Published: 2023
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29. 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 R., Zandstra, Judith, Menikou, Stephanie, Hamilton, Melissa Shea, McArdle, Andrew J., Fischer, Roman, Thorne, Adam M., Huang, Honglei, Tanck, Michael W., Jansen, Machiel H., De, Tisham, Agyeman, Philipp K.A., Von Both, Ulrich, Carrol, Enitan D., Emonts, Marieke, Eleftheriou, Irini, Van der Flier, Michiel, Fink, Colin, Gloerich, Jolein, De Groot, Ronald, Moll, Henriette A., Pokorn, Marko, Pollard, Andrew J., Schlapbach, Luregn J., Tsolia, Maria N., Usuf, Effua, Wright, Victoria J., Yeung, Shunmay, Zavadska, Dace, Zenz, Werner, Coin, Lachlan J.M., Casals-Pascual, Climent, Cunnington, Aubrey J., Martinon-Torres, Federico, Herberg, Jethro A., de Jonge, Marien I., Levin, Michael, Kuijpers, Taco W., Kaforou, Myrsini, Jackson, Heather R., Zandstra, Judith, Menikou, Stephanie, Hamilton, Melissa Shea, McArdle, Andrew J., Fischer, Roman, Thorne, Adam M., Huang, Honglei, Tanck, Michael W., Jansen, Machiel H., De, Tisham, Agyeman, Philipp K.A., Von Both, Ulrich, Carrol, Enitan D., Emonts, Marieke, Eleftheriou, Irini, Van der Flier, Michiel, Fink, Colin, Gloerich, Jolein, De Groot, Ronald, Moll, Henriette A., Pokorn, Marko, Pollard, Andrew J., Schlapbach, Luregn J., Tsolia, Maria N., Usuf, Effua, Wright, Victoria J., Yeung, Shunmay, Zavadska, Dace, Zenz, Werner, Coin, Lachlan J.M., Casals-Pascual, Climent, Cunnington, Aubrey J., Martinon-Torres, Federico, Herberg, Jethro A., de Jonge, Marien I., Levin, Michael, Kuijpers, Taco W., and Kaforou, Myrsini
Abstract: BACKGROUND: Differentiating between self-resolving viral infections and bacterial infections in children who are febrile is a common challenge, causing difficulties in identifying which individuals require antibiotics. Studying the host response to infection can provide useful insights and can lead to the identification of biomarkers of infection with diagnostic potential. This study aimed to identify host protein biomarkers for future development into an accurate, rapid point-of-care test that can distinguish between bacterial and viral infections, by recruiting children presenting to health-care settings with fever or a history of fever in the previous 72 h. METHODS: In this multi-cohort machine learning study, patient data were taken from EUCLIDS, the Swiss Pediatric Sepsis study, the GENDRES study, and the PERFORM study, which were all based in Europe. We generated three high-dimensional proteomic datasets (SomaScan and two via liquid chromatography tandem mass spectrometry, referred to as MS-A and MS-B) using targeted and untargeted platforms (SomaScan and liquid chromatography mass spectrometry). Protein biomarkers were then shortlisted using differential abundance analysis, feature selection using forward selection-partial least squares (FS-PLS; 100 iterations), along with a literature search. Identified proteins were tested with Luminex and ELISA and iterative FS-PLS was done again (25 iterations) on the Luminex results alone, and the Luminex and ELISA results together. A sparse protein signature for distinguishing between bacterial and viral infections was identified from the selected proteins. The performance of this signature was finally tested using Luminex assays and by calculating disease risk scores. FINDINGS:376 children provided serum or plasma samples for use in the discovery of protein biomarkers. 79 serum samples were collected for the generation of the SomaScan dataset, 147 plasma sample
Published: 2023

30. Diagnosis of Multisystem Inflammatory Syndrome in Children by a Whole-Blood Transcriptional Signature

Author: Jackson, Heather R., Miglietta, Luca, Habgood-Coote, Dominic, D'souza, Giselle, Shah, Priyen, Nichols, Samuel, Vito, Ortensia, Powell, Oliver, Davidson, Maisey Salina, Shimizu, Chisato, Agyeman, Philipp K.A., Beudeker, Coco R., Brengel-Pesce, Karen, Carrol, Enitan D., Carter, Michael J., De, Tisham, Eleftheriou, Irini, Emonts, Marieke, Epalza, Cristina, Georgiou, Pantelis, De Groot, Ronald, Fidler, Katy, Fink, Colin, Van Keulen, Daniëlle, Kuijpers, Taco, Moll, Henriette, Papatheodorou, Irene, Paulus, Stephane, Pokorn, Marko, Pollard, Andrew J., Rivero-Calle, Irene, Rojo, Pablo, Secka, Fatou, Schlapbach, Luregn J., Tremoulet, Adriana H., Tsolia, Maria, Usuf, Effua, Van Der Flier, Michiel, Von Both, Ulrich, Vermont, Clementien, Yeung, Shunmay, Zavadska, Dace, Zenz, Werner, Coin, Lachlan J.M., Cunnington, Aubrey, Burns, Jane C., Wright, Victoria, Martinon-Torres, Federico, Herberg, Jethro A., Rodriguez-Manzano, Jesus, Kaforou, Myrsini, Levin, Michael, Jackson, Heather R., Miglietta, Luca, Habgood-Coote, Dominic, D'souza, Giselle, Shah, Priyen, Nichols, Samuel, Vito, Ortensia, Powell, Oliver, Davidson, Maisey Salina, Shimizu, Chisato, Agyeman, Philipp K.A., Beudeker, Coco R., Brengel-Pesce, Karen, Carrol, Enitan D., Carter, Michael J., De, Tisham, Eleftheriou, Irini, Emonts, Marieke, Epalza, Cristina, Georgiou, Pantelis, De Groot, Ronald, Fidler, Katy, Fink, Colin, Van Keulen, Daniëlle, Kuijpers, Taco, Moll, Henriette, Papatheodorou, Irene, Paulus, Stephane, Pokorn, Marko, Pollard, Andrew J., Rivero-Calle, Irene, Rojo, Pablo, Secka, Fatou, Schlapbach, Luregn J., Tremoulet, Adriana H., Tsolia, Maria, Usuf, Effua, Van Der Flier, Michiel, Von Both, Ulrich, Vermont, Clementien, Yeung, Shunmay, Zavadska, Dace, Zenz, Werner, Coin, Lachlan J.M., Cunnington, Aubrey, Burns, Jane C., Wright, Victoria, Martinon-Torres, Federico, Herberg, Jethro A., Rodriguez-Manzano, Jesus, Kaforou, Myrsini, and Levin, Michael
Abstract: Background: To identify a diagnostic blood transcriptomic signature that distinguishes multisystem inflammatory syndrome in children (MIS-C) from Kawasaki disease (KD), bacterial infections, and viral infections. Methods: Children presenting with MIS-C to participating hospitals in the United Kingdom and the European Union between April 2020 and April 2021 were prospectively recruited. Whole-blood RNA Sequencing was performed, contrasting the transcriptomes of children with MIS-C (n = 38) to those from children with KD (n = 136), definite bacterial (DB; n = 188) and viral infections (DV; n = 138). Genes significantly differentially expressed (SDE) between MIS-C and comparator groups were identified. Feature selection was used to identify genes that optimally distinguish MIS-C from other diseases, which were subsequently translated into RT-qPCR assays and evaluated in an independent validation set comprising MIS-C (n = 37), KD (n = 19), DB (n = 56), DV (n = 43), and COVID-19 (n = 39). Results: In the discovery set, 5696 genes were SDE between MIS-C and combined comparator disease groups. Five genes were identified as potential MIS-C diagnostic biomarkers (HSPBAP1, VPS37C, TGFB1, MX2, and TRBV11-2), achieving an AUC of 96.8% (95% CI: 94.6%-98.9%) in the discovery set, and were translated into RT-qPCR assays. The RT-qPCR 5-gene signature achieved an AUC of 93.2% (95% CI: 88.3%-97.7%) in the independent validation set when distinguishing MIS-C from KD, DB, and DV. Conclusions: MIS-C can be distinguished from KD, DB, and DV groups using a 5-gene blood RNA expression signature. The small number of genes in the signature and good performance in both discovery and validation sets should enable the development of a diagnostic test for MIS-C.
Published: 2023

31. Emergency medical services utilisation among febrile children attending emergency departments across Europe:an observational multicentre study

Author: Tan, Chantal D., Vermont, Clementien L., Zachariasse, Joany, von Both, Ulrich, Eleftheriou, Irini, Emonts, Marieke, van der Flier, Michiel, Herberg, Jethro, Kohlmaier, Benno, Levin, Michael, Lim, Emma, Maconochie, Ian, Martinon-Torres, Federico, Nijman, Ruud G., Pokorn, Marko, Rivero-Calle, Irene, Tsolia, Maria, Zenz, Werner, Zavadska, Dace, Moll, Henriëtte A., Carrol, Enitan D., Cunnington, Aubrey, De, Tisham, Kaforou, Myrsini, Hagedoorn, Nienke N., Dik, W., Stocker, Martin, Groot, Ronald de, Willems, Esther, Haan, L. de, Neeleman, C., Tramper-Stranders, G. A., Baas, Bryan, Kloosterhuis, Lieke, Oosthoek, Wilma, Vries, Gabriella de, Velden, Fabian van der, Haas, N., Berg, J. M.van den, Barendregt, A. M., Tan, Chantal D., Vermont, Clementien L., Zachariasse, Joany, von Both, Ulrich, Eleftheriou, Irini, Emonts, Marieke, van der Flier, Michiel, Herberg, Jethro, Kohlmaier, Benno, Levin, Michael, Lim, Emma, Maconochie, Ian, Martinon-Torres, Federico, Nijman, Ruud G., Pokorn, Marko, Rivero-Calle, Irene, Tsolia, Maria, Zenz, Werner, Zavadska, Dace, Moll, Henriëtte A., Carrol, Enitan D., Cunnington, Aubrey, De, Tisham, Kaforou, Myrsini, Hagedoorn, Nienke N., Dik, W., Stocker, Martin, Groot, Ronald de, Willems, Esther, Haan, L. de, Neeleman, C., Tramper-Stranders, G. A., Baas, Bryan, Kloosterhuis, Lieke, Oosthoek, Wilma, Vries, Gabriella de, Velden, Fabian van der, Haas, N., Berg, J. M.van den, and Barendregt, A. M.
Abstract: Children constitute 6–10% of all patients attending the emergency department (ED) by emergency medical services (EMS). However, discordant EMS use in children occurs in 37–61% with fever as an important risk factor. We aimed to describe EMS utilisation among febrile children attending European EDs. This study is part of an observational multicentre study assessing management and outcome in febrile children up to 18 years (MOFICHE) attending twelve EDs in eight European countries. Discordant EMS use was defined as the absence of markers of urgency including intermediate/high triage urgency, advanced diagnostics, treatment, and admission in children transferred by EMS. Multivariable logistic regression analyses were performed for the association between (1) EMS use and markers of urgency, and (2) patient characteristics and discordant EMS use after adjusting all analyses for the covariates age, gender, visiting hours, presenting symptoms, and ED setting. A total of 5464 (15%, range 0.1–42%) children attended the ED by EMS. Markers of urgency were more frequently present in the EMS group compared with the non-EMS group. Discordant EMS use occurred in 1601 children (29%, range 1–59%). Age and gender were not associated with discordant EMS use, whereas neurological symptoms were associated with less discordant EMS use (aOR 0.2, 95%CI 0.1–0.2), and attendance out of office hours was associated with more discordant EMS use (aOR 1.6, 95%CI 1.4–1.9). Settings with higher percentage of self-referrals to the ED had more discordant EMS use (p < 0.05). Conclusion: There is large practice variation in EMS use in febrile children attending European EDs. Markers of urgency were more frequently present in children in the EMS group. However, discordant EMS use occurred in 29%. Further research is needed on non-medical factors influencing discordant EMS use in febrile children across Europe, so that pre-emptive strategies can be implemented. What is Known: •Children constitute a
Published: 2023

32. European study confirms the combination of fever and petechial rash as an important warning sign for childhood sepsis and meningitis

Author: Kohlmaier, Benno, Leitner, Manuel, Hagedoorn, Nienke N., Borensztajn, Dorine M., von Both, Ulrich, Carrol, Enitan D., Emonts, Marieke, van der Flier, Michiel, de Groot, Ronald, Herberg, Jethro, Levin, Michael, Lim, Emma, Maconochie, Ian K., Martinon-Torres, Federico, Nijman, Ruud G., Pokorn, Marko, Rivero-Calle, Irene, Tan, Chantal D., Tsolia, Maria, Vermont, Clementien L., Zachariasse, Joany M., Zavadska, Dace, Moll, Henriette A., Zenz, Werner, Kohlmaier, Benno, Leitner, Manuel, Hagedoorn, Nienke N., Borensztajn, Dorine M., von Both, Ulrich, Carrol, Enitan D., Emonts, Marieke, van der Flier, Michiel, de Groot, Ronald, Herberg, Jethro, Levin, Michael, Lim, Emma, Maconochie, Ian K., Martinon-Torres, Federico, Nijman, Ruud G., Pokorn, Marko, Rivero-Calle, Irene, Tan, Chantal D., Tsolia, Maria, Vermont, Clementien L., Zachariasse, Joany M., Zavadska, Dace, Moll, Henriette A., and Zenz, Werner
Abstract: Aim: This study investigated febrile children with petechial rashes who presented to European emergency departments (EDs) and investigated the role that mechanical causes played in diagnoses. Methods: Consecutive patients with fever presenting to EDs in 11 European emergency departments in 2017–2018 were enrolled. The cause and focus of infection were identified and a detailed analysis was performed on children with petechial rashes. The results are presented as odds ratios (OR) with 95% confidence intervals (CI). Results: We found that 453/34010 (1.3%) febrile children had petechial rashes. The focus of the infection included sepsis (10/453, 2.2%) and meningitis (14/453, 3.1%). Children with a petechial rash were more likely than other febrile children to have sepsis or meningitis (OR 8.5, 95% CI 5.3–13.1) and bacterial infections (OR 1.4, 95% CI 1.0–1.8) as well as need for immediate life-saving interventions (OR 6.6, 95% CI 4.4–9.5) and intensive care unit admissions (OR 6.5, 95% CI 3.0–12.5). Conclusion: The combination of fever and petechial rash is still an important warning sign for childhood sepsis and meningitis. Ruling out coughing and/or vomiting was insufficient to safely identify low-risk patients.
Published: 2023

33. 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, 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, and Emonts, Marieke
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 (< 18 years old) presented to fifteen European hospitals in nine countries, and one Gambian hospital, with fever or suspected infection and clinical indication for blood investigations. Febrile episodes were assigned clinical phenotypes using the validated PERFORM algorithm. Logistic regression was used to assess the effect size of predictive features of proven/presumed bacterial or viral infection. A total of 599 episodes in 482 children were analysed. Seventy-eight episodes (13.0%) were definite bacterial, 67 episodes probable bacterial (11.2%), and 29 bacterial syndrome (4.8%). Fifty-five were definite viral (9.2%), 49 probable viral (8.2%), and 23 viral syndrome (3.8%). One hundred ninety were unknown bacterial or viral infections (31.7%), and 108 had inflammatory or other non-infectious causes of fever (18.1%). Predictive features of proven/presumed bacterial infection were ill appearance (OR 3.1 (95% CI 2.1–4.6)) and HIV (OR 10.4 (95% CI 2.0–54.4)). Ill appearance reduced the odds of having a proven/presumed viral infection (OR 0.5 (95% CI 0.3–0.9)). A total of 82.1% had new empirical antibiotics started on admission (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 stan
Published: 2023

34. Diagnosis of Multisystem Inflammatory Syndrome in Children by a Whole-Blood Transcriptional Signature

Author: Infectieziekten onderzoek1 (Bont), Infection & Immunity, NVIC bedrijfsvoering, Other research (not in main researchprogram), CDL Onderzoek Pasterkamp, Infectieziekten patientenzorg, Child Health, Jackson, Heather R., Miglietta, Luca, Habgood-Coote, Dominic, D'souza, Giselle, Shah, Priyen, Nichols, Samuel, Vito, Ortensia, Powell, Oliver, Davidson, Maisey Salina, Shimizu, Chisato, Agyeman, Philipp K.A., Beudeker, Coco R., Brengel-Pesce, Karen, Carrol, Enitan D., Carter, Michael J., De, Tisham, Eleftheriou, Irini, Emonts, Marieke, Epalza, Cristina, Georgiou, Pantelis, De Groot, Ronald, Fidler, Katy, Fink, Colin, Van Keulen, Daniëlle, Kuijpers, Taco, Moll, Henriette, Papatheodorou, Irene, Paulus, Stephane, Pokorn, Marko, Pollard, Andrew J., Rivero-Calle, Irene, Rojo, Pablo, Secka, Fatou, Schlapbach, Luregn J., Tremoulet, Adriana H., Tsolia, Maria, Usuf, Effua, Van Der Flier, Michiel, Von Both, Ulrich, Vermont, Clementien, Yeung, Shunmay, Zavadska, Dace, Zenz, Werner, Coin, Lachlan J.M., Cunnington, Aubrey, Burns, Jane C., Wright, Victoria, Martinon-Torres, Federico, Herberg, Jethro A., Rodriguez-Manzano, Jesus, Infectieziekten onderzoek1 (Bont), Infection & Immunity, NVIC bedrijfsvoering, Other research (not in main researchprogram), CDL Onderzoek Pasterkamp, Infectieziekten patientenzorg, Child Health, Jackson, Heather R., Miglietta, Luca, Habgood-Coote, Dominic, D'souza, Giselle, Shah, Priyen, Nichols, Samuel, Vito, Ortensia, Powell, Oliver, Davidson, Maisey Salina, Shimizu, Chisato, Agyeman, Philipp K.A., Beudeker, Coco R., Brengel-Pesce, Karen, Carrol, Enitan D., Carter, Michael J., De, Tisham, Eleftheriou, Irini, Emonts, Marieke, Epalza, Cristina, Georgiou, Pantelis, De Groot, Ronald, Fidler, Katy, Fink, Colin, Van Keulen, Daniëlle, Kuijpers, Taco, Moll, Henriette, Papatheodorou, Irene, Paulus, Stephane, Pokorn, Marko, Pollard, Andrew J., Rivero-Calle, Irene, Rojo, Pablo, Secka, Fatou, Schlapbach, Luregn J., Tremoulet, Adriana H., Tsolia, Maria, Usuf, Effua, Van Der Flier, Michiel, Von Both, Ulrich, Vermont, Clementien, Yeung, Shunmay, Zavadska, Dace, Zenz, Werner, Coin, Lachlan J.M., Cunnington, Aubrey, Burns, Jane C., Wright, Victoria, Martinon-Torres, Federico, Herberg, Jethro A., and Rodriguez-Manzano, Jesus
Published: 2023

35. 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 R, Zandstra, Judith, Menikou, Stephanie, Hamilton, Melissa Shea, McArdle, Andrew J, Fischer, Roman, Thorne, Adam M, Huang, Honglei, Tanck, Michael W, Jansen, Machiel H, De, Tisham, Agyeman, Philipp K A; https://orcid.org/0000-0002-8339-5444, von Both, Ulrich; https://orcid.org/0000-0001-8411-1071, Carrol, Enitan D, Emonts, Marieke, Eleftheriou, Irini, Van der Flier, Michiel, Fink, Colin, Gloerich, Jolein, De Groot, Ronald, Moll, Henriette A, Pokorn, Marko, Pollard, Andrew J; https://orcid.org/0000-0001-7361-719X, Schlapbach, Luregn J; https://orcid.org/0000-0003-2281-2598, Tsolia, Maria N, Usuf, Effua, Wright, Victoria J; https://orcid.org/0000-0001-7826-1516, Yeung, Shunmay, Zavadska, Dace, Zenz, Werner, et al, Jackson, Heather R, Zandstra, Judith, Menikou, Stephanie, Hamilton, Melissa Shea, McArdle, Andrew J, Fischer, Roman, Thorne, Adam M, Huang, Honglei, Tanck, Michael W, Jansen, Machiel H, De, Tisham, Agyeman, Philipp K A; https://orcid.org/0000-0002-8339-5444, von Both, Ulrich; https://orcid.org/0000-0001-8411-1071, Carrol, Enitan D, Emonts, Marieke, Eleftheriou, Irini, Van der Flier, Michiel, Fink, Colin, Gloerich, Jolein, De Groot, Ronald, Moll, Henriette A, Pokorn, Marko, Pollard, Andrew J; https://orcid.org/0000-0001-7361-719X, Schlapbach, Luregn J; https://orcid.org/0000-0003-2281-2598, Tsolia, Maria N, Usuf, Effua, Wright, Victoria J; https://orcid.org/0000-0001-7826-1516, Yeung, Shunmay, Zavadska, Dace, Zenz, Werner, and et al
Abstract: Background: Differentiating between self-resolving viral infections and bacterial infections in children who are febrile is a common challenge, causing difficulties in identifying which individuals require antibiotics. Studying the host response to infection can provide useful insights and can lead to the identification of biomarkers of infection with diagnostic potential. This study aimed to identify host protein biomarkers for future development into an accurate, rapid point-of-care test that can distinguish between bacterial and viral infections, by recruiting children presenting to health-care settings with fever or a history of fever in the previous 72 h. Methods: In this multi-cohort machine learning study, patient data were taken from EUCLIDS, the Swiss Pediatric Sepsis study, the GENDRES study, and the PERFORM study, which were all based in Europe. We generated three high-dimensional proteomic datasets (SomaScan and two via liquid chromatography tandem mass spectrometry, referred to as MS-A and MS-B) using targeted and untargeted platforms (SomaScan and liquid chromatography mass spectrometry). Protein biomarkers were then shortlisted using differential abundance analysis, feature selection using forward selection-partial least squares (FS-PLS; 100 iterations), along with a literature search. Identified proteins were tested with Luminex and ELISA and iterative FS-PLS was done again (25 iterations) on the Luminex results alone, and the Luminex and ELISA results together. A sparse protein signature for distinguishing between bacterial and viral infections was identified from the selected proteins. The performance of this signature was finally tested using Luminex assays and by calculating disease risk scores. Findings: 376 children provided serum or plasma samples for use in the discovery of protein biomarkers. 79 serum samples were collected for the generation of the SomaScan dataset, 147 plasma samples for the MS-A dataset, and 150 plasma samples for the MS
Published: 2023

36. Emergency medical services utilisation among febrile children attending emergency departments across Europe: an observational multicentre study

Author: Tan, Chantal D, Vermont, Clementien L, Zachariasse, Joany M, von Both, Ulrich; https://orcid.org/0000-0001-8411-1071, Eleftheriou, Irini, Emonts, Marieke, van der Flier, Michiel, Herberg, Jethro, Kohlmaier, Benno, Levin, Michael, Lim, Emma, Maconochie, Ian K, Martinón-Torres, Federico; https://orcid.org/0000-0002-9023-581X, Nijman, Ruud G, Pokorn, Marko, Rivero-Calle, Irene, Tsolia, Maria, Zenz, Werner, Zavadska, Dace, Moll, Henriëtte A, Carrol, Enitan D, PERFORM consortium (Personalised Risk assessment in febrile chil, Tan, Chantal D, Vermont, Clementien L, Zachariasse, Joany M, von Both, Ulrich; https://orcid.org/0000-0001-8411-1071, Eleftheriou, Irini, Emonts, Marieke, van der Flier, Michiel, Herberg, Jethro, Kohlmaier, Benno, Levin, Michael, Lim, Emma, Maconochie, Ian K, Martinón-Torres, Federico; https://orcid.org/0000-0002-9023-581X, Nijman, Ruud G, Pokorn, Marko, Rivero-Calle, Irene, Tsolia, Maria, Zenz, Werner, Zavadska, Dace, Moll, Henriëtte A, Carrol, Enitan D, and PERFORM consortium (Personalised Risk assessment in febrile chil
Abstract: Children constitute 6-10% of all patients attending the emergency department (ED) by emergency medical services (EMS). However, discordant EMS use in children occurs in 37-61% with fever as an important risk factor. We aimed to describe EMS utilisation among febrile children attending European EDs. This study is part of an observational multicentre study assessing management and outcome in febrile children up to 18 years (MOFICHE) attending twelve EDs in eight European countries. Discordant EMS use was defined as the absence of markers of urgency including intermediate/high triage urgency, advanced diagnostics, treatment, and admission in children transferred by EMS. Multivariable logistic regression analyses were performed for the association between (1) EMS use and markers of urgency, and (2) patient characteristics and discordant EMS use after adjusting all analyses for the covariates age, gender, visiting hours, presenting symptoms, and ED setting. A total of 5464 (15%, range 0.1-42%) children attended the ED by EMS. Markers of urgency were more frequently present in the EMS group compared with the non-EMS group. Discordant EMS use occurred in 1601 children (29%, range 1-59%). Age and gender were not associated with discordant EMS use, whereas neurological symptoms were associated with less discordant EMS use (aOR 0.2, 95%CI 0.1-0.2), and attendance out of office hours was associated with more discordant EMS use (aOR 1.6, 95%CI 1.4-1.9). Settings with higher percentage of self-referrals to the ED had more discordant EMS use (p < 0.05). Conclusion: There is large practice variation in EMS use in febrile children attending European EDs. Markers of urgency were more frequently present in children in the EMS group. However, discordant EMS use occurred in 29%. Further research is needed on non-medical factors influencing discordant EMS use in febrile children across Europe, so that pre-emptive strategies can be implemented. What is Known: •Children constitute around
Published: 2023

37. Correction to: 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; https://orcid.org/0000-0001-8411-1071, Kolberg, Laura; https://orcid.org/0000-0002-3311-8254, Carrol, Enitan D, Khanijau, Aakash, Herberg, Jethro A; https://orcid.org/0000-0001-6941-6491, De, Tisham, Galassini, Rachel, Kuijpers, Taco W, Martinón-Torres, Federico; https://orcid.org/0000-0002-9023-581X, Rivero-Calle, Irene, Vermont, Clementien L, Hagedoorn, Nienke N, Pokorn, Marko, Pollard, Andrew J; https://orcid.org/0000-0001-7361-719X, Schlapbach, Luregn J; https://orcid.org/0000-0003-2281-2598, Tsolia, Maria, Elefhteriou, Irini, Yeung, Shunmay, Zavadska, Dace, Fink, Colin, Voice, Marie, Zenz, Werner, Kohlmaier, Benno, Agyeman, Philipp K A; https://orcid.org/0000-0002-8339-5444, Usuf, Effua, Secka, Fatou, et al, van der Velden, Fabian J S, de Vries, Gabriella, Martin, Alexander, Lim, Emma, von Both, Ulrich; https://orcid.org/0000-0001-8411-1071, Kolberg, Laura; https://orcid.org/0000-0002-3311-8254, Carrol, Enitan D, Khanijau, Aakash, Herberg, Jethro A; https://orcid.org/0000-0001-6941-6491, De, Tisham, Galassini, Rachel, Kuijpers, Taco W, Martinón-Torres, Federico; https://orcid.org/0000-0002-9023-581X, Rivero-Calle, Irene, Vermont, Clementien L, Hagedoorn, Nienke N, Pokorn, Marko, Pollard, Andrew J; https://orcid.org/0000-0001-7361-719X, Schlapbach, Luregn J; https://orcid.org/0000-0003-2281-2598, Tsolia, Maria, Elefhteriou, Irini, Yeung, Shunmay, Zavadska, Dace, Fink, Colin, Voice, Marie, Zenz, Werner, Kohlmaier, Benno, Agyeman, Philipp K A; https://orcid.org/0000-0002-8339-5444, Usuf, Effua, Secka, Fatou, and et al
Published: 2023

38. Identification of regulatory variants associated with genetic susceptibility to meningococcal disease

Author: Borghini, Lisa, Png, Eileen, Binder, Alexander, Wright, Victoria J., Pinnock, Ellie, de Groot, Ronald, Hazelzet, Jan, Emonts, Marieke, Van der Flier, Michiel, Schlapbach, Luregn J., Anderson, Suzanne, Secka, Fatou, Salas, Antonio, Fink, Colin, Carrol, Enitan D., Pollard, Andrew J., Coin, Lachlan J., Kuijpers, Taco W., Martinon-Torres, Federico, Zenz, Werner, Levin, Michael, Hibberd, Martin L., Davila, Sonia, and EUCLIDS consortium
Published: 2019
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39. Correction to: Group A streptococcal disease in paediatric inpatients: a European perspective

Author: Boeddha, Navin P, Atkins, Lucy, de Groot, Ronald, Driessen, Gertjan, Hazelzet, Jan, Zenz, Werner, Carrol, Enitan D, Anderson, Suzanne T, Martinon-Torres, Federico, Agyeman, Philipp K A, Galassini, Rachel, Herberg, Jethro, Levin, Michael, Schlapbach, Luregn J, and Emonts, Marieke
Subjects: Pediatrics, Perinatology and Child Health, Correction, 610 Medizin und Gesundheit
Abstract: UNLABELLED: Group A streptococcal (GAS) disease shows increasing incidence worldwide. We characterised children admitted with GAS infection to European hospitals and studied risk factors for severity and disability. This is a prospective, multicentre, cohort study (embedded in EUCLIDS and the Swiss Pediatric Sepsis Study) including 320 children, aged 1 month to 18 years, admitted with GAS infection to 41 hospitals in 6 European countries from 2012 to 2016. Demographic, clinical, microbiological and outcome data were collected. A total of 195 (61%) patients had sepsis. Two hundred thirty-six (74%) patients had GAS detected from a normally sterile site. The most common infection sites were the lower respiratory tract (LRTI) (22%), skin and soft tissue (SSTI) (23%) and bone and joint (19%). Compared to patients not admitted to PICU, patients admitted to PICU more commonly had LRTI (39 vs 8%), infection without a focus (22 vs 8%) and intracranial infection (9 vs 3%); less commonly had SSTI and bone and joint infections (p CONCLUSION: In an era of observed marked reduction in vaccine-preventable infections, GAS infection requiring hospital admission is still associated with significant severe disease in younger children, and short- and long-term morbidity. Further advances are required in the prevention and early recognition of GAS disease.WHAT IS KNOWN: • Despite temporal and geographical variability, there is an increase of incidence of infection with group A streptococci. However, data on the epidemiology of group A streptococcal infections in European children is limited.WHAT IS NEW: • In a large, prospective cohort of children with community-acquired bacterial infection requiring hospitalisation in Europe, GAS was the most frequent pathogen, with 12% disability at discharge, and 2% mortality in patients with GAS infection. • In children with GAS sepsis, IVIG was used in only 4.6% of patients and clindamycin in 29% of patients.
Published: 2023

40. Group a Streptococcal Disease in Paediatric Inpatients: a European Perspective

Author: Boeddha, Navin P., primary, Atkins, Lucy, additional, De Groot, Ronald, additional, Driessen, Gertjan, additional, Hazelzet, Jan, additional, Zenz, Werner, additional, Carrol, Enitan D., additional, Anderson, Suzanne T., additional, Martinon-Torres, Federico, additional, Agyeman, Philipp, additional, Galassini, Rachel, additional, Herberg, Jethro, additional, Levin, Michael, additional, Schlapbach, Luregn J., additional, and Emonts, Marieke, additional
Published: 2022
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41. Cardiac and Pulmonary Cystic Echinococcosis With Massive Obstruction of the Pulmonary Vessel System in a 16-Year-Old Girl

Author: Kohlmaier, Benno, Trobisch, Andreas, Pfurtscheller, Klaus, Knez, Igor, Klepetko, Walter, Pilhatsch, Alexander, Schweintzger, Sabrina, and Zenz, Werner
Published: 2018
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42. 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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43. 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

44. Impfungen bei Immundefekten/Immunsuppression – Expertenstatement und Empfehlungen

Author: Wiedermann, Ursula, Sitte, Harald H., Burgmann, Heinz, Eser, Alexander, Falb, Petra, Holzmann, Heidemarie, Kitchen, Maria, Köller, Marcus, Kollaritsch, Herwig, Kundi, Michael, Lassmann, Hans, Mutz, Ingomar, Pickl, Winfried F., Riedl, Elisabeth, Sibilia, Maria, Thalhammer, Florian, Tucek, Barbara, Zenz, Werner, and Zwiauer, Karl
Published: 2016
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45. Prematurity and the burden of influenza and respiratory syncytial virus disease

Author: Resch, Bernhard, Kurath-Koller, Stefan, Eibisberger, Monika, and Zenz, Werner
Published: 2016
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46. Febrile illness in high-risk children: a prospective, international observational study

Author: Velden, Fabian J.S. van der, primary, de Vries, Gabriella, additional, Martin, Alexander, additional, Lim, Emma, additional, von Both, Ulrich, additional, Kolberg, Laura, additional, Carrol, Enitan D., additional, Khanijau, Aakash, additional, Herberg, Jethro A., additional, De, Tisham, additional, Galassini, Rachel, additional, Kuijpers, Taco W., additional, Martinón-Torres, Federico, additional, Rivero-Calle, Irene, additional, Vermont, Clementien L., additional, Hagedoorn, Nienke N., additional, Pokorn, Marko, additional, Pollard, Andrew J., additional, Schlapbach, Luregn J., additional, Tsolia, Maria, additional, Elefhteriou, Irini, additional, Yeung, Shunmay, additional, Zavadska, Dace, additional, Fink, Colin, additional, Voice, Marie, additional, Zenz, Werner, additional, Kohlmaier, Benno, additional, Agyeman, Philipp K.A., additional, Usuf, Effua, additional, Secka, Fatou, additional, de Groot, Ronald, additional, Levin, Michael, additional, Flier, Michiel van der, additional, Emonts, Marieke, additional, and Consortium, PERFORM, additional
Published: 2022
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47. Characteristics and management of adolescents attending the ED with fever:A prospective multicentre study

Author: Borensztajn, Dorine, Hagedoorn, Nienke N., Carrol, Enitan, Von Both, Ulrich, Dewez, Juan Emmanuel, Emonts, Marieke, Van Der Flier, Michiel, De Groot, Ronald, Herberg, Jethro, Kohlmaier, Benno, Levin, Michael, Lim, Emma, Maconochie, Ian, Martinon Torres, Federico, Nijman, Ruud, Pokorn, Marko, Rivero-Calle, Irene, Tsolia, Maria, Vermont, Clementien, Zavadska, Dace, Zenz, Werner, Zachariasse, Joany, Moll, Henriette A., Borensztajn, Dorine, Hagedoorn, Nienke N., Carrol, Enitan, Von Both, Ulrich, Dewez, Juan Emmanuel, Emonts, Marieke, Van Der Flier, Michiel, De Groot, Ronald, Herberg, Jethro, Kohlmaier, Benno, Levin, Michael, Lim, Emma, Maconochie, Ian, Martinon Torres, Federico, Nijman, Ruud, Pokorn, Marko, Rivero-Calle, Irene, Tsolia, Maria, Vermont, Clementien, Zavadska, Dace, Zenz, Werner, Zachariasse, Joany, and Moll, Henriette A.
Abstract: Objective Most studies on febrile children have focused on infants and young children with serious bacterial infection (SBI). Although population studies have described an increased risk of sepsis in adolescents, little is known about febrile adolescents attending the emergency department (ED). We aimed to describe patient characteristics and management of febrile adolescents attending the ED. Design and setting The MOFICHE/PERFORM study (Management and Outcome of Febrile Children in Europe/Personalised Risk assessment in Febrile illness to Optimise Real-life Management across the European Union), a prospective multicentre study, took place at 12 European EDs. Descriptive and multivariable regression analyses were performed, comparing febrile adolescents (12-18 years) with younger children in terms of patient characteristics, markers of disease severity (vital signs, clinical alarming signs), management (diagnostic tests, therapy, admission) and diagnosis (focus, viral/bacterial infection). Results 37 420 encounters were included, of which 2577 (6.9%) were adolescents. Adolescents were more often triaged as highly urgent (38.9% vs 34.5%) and described as ill appearing (23.1% vs 15.6%) than younger children. Increased work of breathing and a non-blanching rash were present less often in adolescents, while neurological signs were present more often (1% vs 0%). C reactive protein tests were performed more frequently in adolescents and were more often abnormal (adjusted OR (aOR) 1.7, 95% CI 1.5 to 1.9). Adolescents were more often diagnosed with SBI (OR 1.8, 95% CI 1.6 to 2.0) and sepsis/meningitis (OR 2.3, 95% CI 1.1 to 5.0) and were more frequently admitted (aOR 1.3, 95% CI 1.2 to 1.4) and treated with intravenous antibiotics (aOR 1.7, 95% CI 1.5 to 2.0). Conclusions Although younger children presented to the ED more frequently, adolescents were more often diagnosed with SBI and sepsis/meningitis. Our data emphasise the importance of awareness of severe infections
Published: 2022

48. Shock Index in the early assessment of febrile children at the emergency department:A prospective multicentre study

Author: Hagedoorn, Nienke N., Zachariasse, Joany M., Borensztajn, Dorine, Adriaansens, Elise, Von Both, Ulrich, Carrol, Enitan D., Eleftheriou, Irini, Emonts, Marieke, Van Der Flier, Michiel, De Groot, Ronald, Herberg, Jethro Adam, Kohlmaier, Benno, Lim, Emma, MacOnochie, Ian, Martinón-Torres, Federico, Nijman, Ruud Gerard, Pokorn, Marko, Rivero-Calle, Irene, Tsolia, Maria, Zavadska, Dace, Zenz, Werner, Levin, Michael, Vermont, Clementien, Moll, Henriette A., Hagedoorn, Nienke N., Zachariasse, Joany M., Borensztajn, Dorine, Adriaansens, Elise, Von Both, Ulrich, Carrol, Enitan D., Eleftheriou, Irini, Emonts, Marieke, Van Der Flier, Michiel, De Groot, Ronald, Herberg, Jethro Adam, Kohlmaier, Benno, Lim, Emma, MacOnochie, Ian, Martinón-Torres, Federico, Nijman, Ruud Gerard, Pokorn, Marko, Rivero-Calle, Irene, Tsolia, Maria, Zavadska, Dace, Zenz, Werner, Levin, Michael, Vermont, Clementien, and Moll, Henriette A.
Abstract: Objective (1) To derive reference values for the Shock Index (heart rate/systolic blood pressure) based on a large emergency department (ED) population of febrile children and (2) to determine the diagnostic value of the Shock Index for serious illness in febrile children. Design/setting Observational study in 11 European EDs (2017-2018). Patients Febrile children with measured blood pressure. Main outcome measures Serious bacterial infection (SBI), invasive bacterial infection (IBI), immediate life-saving interventions (ILSIs) and intensive care unit (ICU) admission. The association between high Shock Index (>95th centile) and each outcome was determined by logistic regression adjusted for age, sex, referral, comorbidity and temperature. Additionally, we calculated sensitivity, specificity and negative/positive likelihood ratios (LRs). Results Of 5622 children, 461 (8.2%) had SBI, 46 (0.8%) had IBI, 203 (3.6%) were treated with ILSI and 69 (1.2%) were ICU admitted. High Shock Index was associated with SBI (adjusted OR (aOR) 1.6 (95% CI 1.3 to 1.9)), ILSI (aOR 2.5 (95% CI 2.0 to 2.9)), ICU admission (aOR 2.2 (95% CI 1.4 to 2.9)) but not with IBI (aOR: 1.5 (95% CI 0.6 to 2.4)). For the different outcomes, sensitivity for high Shock Index ranged from 0.10 to 0.15, specificity ranged from 0.95 to 0.95, negative LRs ranged from 0.90 to 0.95 and positive LRs ranged from 1.8 to 2.8. Conclusions High Shock Index is associated with serious illness in febrile children. However, its rule-out value is insufficient which suggests that the Shock Index is not valuable as a screening tool for all febrile children at the ED.
Published: 2022

49. 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

50. Sex differences in febrile children with respiratory symptoms attending European emergency departments:An observational multicenter study

Author: Tan, Chantal D., el Ouasghiri, Soufiane, von Both, Ulrich, Carrol, Enitan D., Emonts, Marieke, van der Flier, Michiel, de Groot, Ronald, Herberg, Jethro, Kohlmaier, Benno, Levin, Michael, Lim, Emma, Maconochie, Ian K., Martinon-Torres, Federico, Nijman, Ruud G., Pokorn, Marko, Rivero-Calle, Irene, Tsolia, Maria, Vermont, Clementien L., Zenz, Werner, Zavadska, Dace, Moll, Henriette A., Zachariasse, Joany M., Tan, Chantal D., el Ouasghiri, Soufiane, von Both, Ulrich, Carrol, Enitan D., Emonts, Marieke, van der Flier, Michiel, de Groot, Ronald, Herberg, Jethro, Kohlmaier, Benno, Levin, Michael, Lim, Emma, Maconochie, Ian K., Martinon-Torres, Federico, Nijman, Ruud G., Pokorn, Marko, Rivero-Calle, Irene, Tsolia, Maria, Vermont, Clementien L., Zenz, Werner, Zavadska, Dace, Moll, Henriette A., and Zachariasse, Joany M.
Abstract: Objective To assess sex differences in presentation and management of febrile children with respiratory symptoms attending European Emergency Departments. Design and setting An observational study in twelve Emergency Departments in eight European countries. Patients Previously healthy children aged 0-<18 years with fever (≥ 38°C) at the Emergency Department or in the consecutive three days before Emergency Department visit and respiratory symptoms were included. Main outcome measures The main outcomes were patient characteristics and management defined as diagnostic tests, treatment and admission. Descriptive statistics were used for patient characteristics and management stratified by sex. Multivariable logistic regression analyses were performed for the association between sex and management with adjustment for age, disease severity and Emergency Department. Additionally, subgroup analyses were performed in children with upper and lower respiratory tract infections and in children below five years. Results We included 19,781 febrile children with respiratory symptoms. The majority were boys (54%), aged 1-5 years (58%) and triaged as low urgent (67%). Girls presented less frequently with tachypnea (15% vs 16%, p = 0.002) and increased work of breathing (8% vs 12%, p<0.001) compared with boys. Girls received less inhalation medication than boys (aOR 0.82, 95% CI 0.74-0.90), but received antibiotic treatment more frequently than boys (aOR 1.09, 95% CI 1.02-1.15), which is associated with a higher prevalence of urinary tract infections. Amongst children with a lower respiratory tract infection and children below five years girls received less inhalation medication than boys (aOR 0.77, 95% CI 0.66-0.89; aOR 0.80, 95% CI 0.72-0.90). Conclusions Sex differences concerning presentation and management are present in previously healthy febrile children with respiratory symptoms presenting to the Emergency Department. Future research should focus on whether these di
Published: 2022

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