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4. Psychiatric symptoms in people living with HIV: prevalences, interactions and consequences

Author

Meeder, E. M., primary, Blaauw, M., additional, van Eekeren, L. E., additional, Groenendijk, A., additional, Vos, W. A., additional, de Mast, Q., additional, Blok, W. L., additional, Verbon, A., additional, Berrevoets, M. A., additional, van Lunzen, J., additional, Joosten, L., additional, Netea, M., additional, Matzaraki, V., additional, van der Ven, A. J., additional, and Schellekens, A. F., additional

Published
2023
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6. Lupus anticoagulant associates with thrombosis in patients with COVID-19 admitted to intensive care units

Author

Noordermeer, Tessa, Schutgens, Roger E. G., Visser, Chantal, Rademaker, Emma, de Maat, Moniek P. M., Jansen, A. J. Gerard, Limper, Maarten, Cremer, Olaf L., Kruip, Marieke J. H. A., Endeman, Henrik, Maas, Coen, de Laat, Bas, Urbanus, Rolf T., van de Beek, D., Brouwer, M. C., de Bruin, S., Coppens, M., van Es, N., van Haaps, T. F., Juffermans, N. P., Muller, M. C. A., Vlaar, A. P. J., Hertogh, C. M. P. M., Heunks, L. M. A., Hugtenburg, J. G., van Kooten, J., Nossent, E. J., Smulders, Y., Tuinman, P. R., Noordegraaf, A. Vonk, Grootenboers, M. J. J. H., van Guldener, C., Kant, M., Lansbergen, A., Faber, J., Hajer, G., Stemerdink, A., van den Akker, J., Bierings, R., Endeman, H., Goeijenbier, M., Hunfeld, N. G. M., van Gorp, E. C. M., Gommers, D. A. M. P. J., Koopmans, M. P. G., Kruip, M. J. H. A., Kuiken, T., Langerak, T., Leebeek, Lauw, M. N., de Maat, M. P. M., Noack, D., Paats, M. S., Raadsen, M. P., Rockx, B., Rokx, C., Schurink, C. A. M., Tong-Minh, K., van den Toorn, L., den Uil, C. A., Visser, C., Boutkourt, F., Roest, T., Douma, R. A., de Haan, L. R., ten Wolde, M., Bemelmans, R. H. H., Festen, B., Stads, S., de Jager, C. P. C., Simons, K. S., Antoni, M. L., Bos, M. H., Burggraaf, J. L. I., Cannegieter, S. C., Eikenboom, H. C. J., den Exter, P. L., Geelhoed, J. J. M., Huisman, M. V., de Jonge, E., Kaptein, F. H. J., Klok, F. A., Kroft, L. J. M., Lijfering, W. M., Nab, L., Ninaber, M. K., Putter, H., Ramai, S. R. S., da Rocha Rondon, A. M., Roukens, A. H. E., Stals, M. A. M., Versteeg, H. H., Vliegen, H. W., van Vlijmen, B. J. M., van de Berg, T., Bruggemann, R., van Bussel, B. C. T., ten Cate, H., ten Cate-Hoek, A., Hackeng, T. M., Henskens, ir. Y., Hulshof, A., Mulder, M., Olie, R. H., Schurgers, L., Spaetgens, B., Spronk, H., Spruit, M. A., Winckers, K., Nieuwenhuizen, L., Franken, B., Schrover, I. M., de Waal, E. G. M., Beishuizen, A., Cornet, A., Krabbe, J., Kramers, K., Leentjens, J., de Mast, Q., Middeldorp, S., Brouwer, R. E., Ellerbroek, J. L. J., Tijmensen, J., Hovens, M. M. C., Oostdijk, E. A. N., Westerhof, B. D., Faber, L. M., van den Biggelaar, M., Meijers, J. C. M., Voorberg, J., Kevenaar, M. E., Soei, Y. L., Wils, E. J., Croles, F. N., de Laat, B., Kamphuisen, P. W., Vink, R., Lisman, T., Meijer, K., van Tichelaar, Y. I. G., Cremer, O. L., Geersing, G., Kaasjager, H. A. H., Kusadasi, N., Huisman, A., Maas, C., Nijkeuter, M., Schutgens, R. E. G., Creveldkliniek, Van, Urbanus, R. T., Westerink, J., Faber, H. J., Koster, S. C. E., van Montfort, P., van Twist, D. J. L., RS: Carim - B01 Blood proteins & engineering, Biochemie, Hematology, Intensive Care, Neurology, ANS - Neuroinfection & -inflammation, Intensive Care Medicine, ACS - Pulmonary hypertension & thrombosis, AII - Inflammatory diseases, Vascular Medicine, ACS - Amsterdam Cardiovascular Sciences, Graduate School, ACS - Microcirculation, Medical Microbiology and Infection Prevention, ARD - Amsterdam Reproduction and Development, Experimental Vascular Medicine, Landsteiner Laboratory, ACS - Atherosclerosis & ischemic syndromes, Elderly care medicine, APH - Aging & Later Life, Clinical pharmacology and pharmacy, APH - Health Behaviors & Chronic Diseases, Pulmonary medicine, Internal medicine, ACS - Diabetes & metabolism, Intensive care medicine, General practice, and Amsterdam Gastroenterology Endocrinology Metabolism

Subjects
lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], lupus anticoagulant, risk factor, critically ill, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], COVID-19, Hematology, thrombosis, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18]
Abstract

Contains fulltext : 286889.pdf (Publisher’s version ) (Open Access) BACKGROUND: Thrombosis is a frequent and severe complication in patients with coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU). Lupus anticoagulant (LA) is a strong acquired risk factor for thrombosis in various diseases and is frequently observed in patients with COVID-19. Whether LA is associated with thrombosis in patients with severe COVID-19 is currently unclear. OBJECTIVE: To investigate if LA is associated with thrombosis in critically ill patients with COVID-19. PATIENTS/METHODS: The presence of LA and other antiphospholipid antibodies was assessed in patients with COVID-19 admitted to the ICU. LA was determined with dilute Russell's viper venom time (dRVVT) and LA-sensitive activated partial thromboplastin time (aPTT) reagents. RESULTS: Of 169 patients with COVID-19, 116 (69%) tested positive for at least one antiphospholipid antibody upon admission to the ICU. Forty (24%) patients tested positive for LA; of whom 29 (17%) tested positive with a dRVVT, 19 (11%) tested positive with an LA-sensitive aPTT, and 8 (5%) tested positive on both tests. Fifty-eight (34%) patients developed thrombosis after ICU admission. The odds ratio (OR) for thrombosis in patients with LA based on a dRVVT was 2.5 (95% confidence interval [CI], 1.1-5.7), which increased to 4.5 (95% CI, 1.4-14.3) in patients at or below the median age in this study (64 years). LA positivity based on a dRVVT or LA-sensitive aPTT was only associated with thrombosis in patients aged less than 65 years (OR, 3.8; 95% CI, 1.3-11.4) and disappeared after adjustment for C-reactive protein. CONCLUSION: Lupus anticoagulant on admission is strongly associated with thrombosis in critically ill patients with COVID-19, especially in patients aged less than 65 years.

Published
2022

10. ESICM LIVES 2016: part one: Milan, Italy. 1-5 October 2016

Author

Bos, L., Schouten, L., van Vught, L., Wiewel, M., Ong, D., Cremer, O., Artigas, A., Martin-Loeches, I., Hoogendijk, A., van der Poll, T., Horn, J., Juffermans, N., Schultz, M., de Prost, N., Pham, T., Carteaux, G., Dessap, A. Mekontso, Brun-Buisson, C., Fan, E., Bellani, G., Laffey, J., Mercat, A., Brochard, L., Maitre, B., Howells, P. A., Thickett, D. R., Knox, C., Park, D. P., Gao, F., Tucker, O., Whitehouse, T., McAuley, D. F., Perkins, G. D., Pham, T., Laffey, J., Bellani, G., Fan, E., Pisani, L., Roozeman, J. P., Simonis, F. D., Giangregorio, A., Schouten, L. R., Van der Hoeven, S. M., Horn, J., Neto, A. Serpa, Festic, E., Dondorp, A. M., Grasso, S., Bos, L. D., Schultz, M. J., Koster-Brouwer, M., Verboom, D., Scicluna, B., van de Groep, K., Frencken, J., Schultz, M., van der Poll, T., Bonten, M., Cremer, O., Ko, J. I., Kim, K. S., Suh, G. J., Kwon, W. Y., Kim, K., Shin, J. H., Ranzani, O. T., Prina, E., Menendez, R., Ceccato, A., Mendez, R., Cilloniz, C., Gabarrus, A., Ferrer, M., Torres, A., Urbano, A., Zhang, L. A., Swigon, D., Pike, F., Parker, R. S., Clermont, G., Scheer, C., Kuhn, S. O., Modler, A., Vollmer, M., Fuchs, C., Hahnenkamp, K., Rehberg, S., Gründling, M., Taggu, A., Darang, N., Öveges, N., László, I., Tánczos, K., Németh, M., Lebák, G., Tudor, B., Érces, D., Kaszaki, J., Huber, W., Trásy, D., Molnár, Z., Ferrara, G., Edul, V. S. Kanoore, Canales, H. S., Martins, E., Canullán, C., Murias, G., Pozo, M. O., Eguillor, J. F. Caminos, Buscetti, M. G., Ince, C., Dubin, A., Aya, H. D., Rhodes, A., Fletcher, N., Grounds, R. M., Cecconi, M., Jacquet-Lagrèze, M., Riche, M., Schweizer, R., Portran, P., Fornier, W., Lilot, M., Neidecker, J., Fellahi, J. L., Escoresca-Ortega, A., Gutiérrez-Pizarraya, A., Charris-Castro, L., Corcia-Palomo, Y., Fernandez-Delgado, E., Garnacho-Montero, J., Roger, C., Muller, L., Elotmani, L., Lipman, J., Lefrant, J. Y., Roberts, J. A., Muñoz-Bermúdez, R., Samper, M., Climent, C., Vasco, F., Sara, V., Luque, S., Campillo, N., Cerrato, S. Grau, Masclans, J. R., Alvarez-Lerma, F., Brugger, S. Carvalho, Jimenez, G. Jimenez, Torner, M. Miralbés, Cabello, J. Trujillano, Garrido, B. Balsera, Casals, X. Nuvials, Gaite, F. Barcenilla, Vidal, M. Vallverdú, Martínez, M. Palomar, Gusarov, V., Shilkin, D., Dementienko, M., Nesterova, E., Lashenkova, N., Kuzovlev, A., Zamyatin, M., Demoule, A., Carreira, S., Lavault, S., Palancca, O., Morawiec, E., Mayaux, J., Arnulf, I., Similowski, T., Rasmussen, B. S., Maltesen, R. G., Hanifa, M., Pedersen, S., Kristensen, S. R., Wimmer, R., Panigada, M., Bassi, G. Li, Ranzani, O. T., Kolobow, T., Zanella, A., Cressoni, M., Berra, L., Parrini, V., Kandil, H., Salati, G., Livigni, S., Amatu, A., Andreotti, A., Tagliaferri, F., Moise, G., Mercurio, G., Costa, A., Vezzani, A., Lindau, S., Babel, J., Cavana, M., Consonni, D., Pesenti, A., Gattinoni, L., Torres, A., Mansouri, P., Zand, F., Zahed, L., Dehghanrad, F., Bahrani, M., Ghorbani, M., Cambiaghi, B., Moerer, O., Mauri, T., Kunze-Szikszay, N., Ritter, C., Pesenti, A., Quintel, M., Vilander, L. M., Kaunisto, M. A., Vaara, S. T., Pettilä, V., Mulier, J. L. G. Haitsma, Rozemeijer, S., Spoelstra-de Man, A. M. E., Elbers, P. E., Tuinman, P. R., de Waard, M. C., Oudemans-van Straaten, H. M., Liberatore, A. M. A., Souza, R. B., Martins, A. M. C. R. P. F., Vieira, J. C. F., Koh, I. H. J., Martínez, M. Galindo, Sánchez, R. Jiménez, Gascón, L. Martínez, Mulero, M. D. Rodríguez, Freire, A. Ortín, Muñoz, A. Ojados, Acebes, S. Rebollo, Martínez, Á. Fernández, Aliaga, S. Moreno, Para, L. Herrera, Payá, J. Murcia, Mulero, F. Rodríguez, Guerci, P., Ince, Y., Heeman, P., Ergin, B., Ince, C., Uz, Z., Massey, M., Ince, Y., Papatella, R., Bulent, E., Guerci, P., Toraman, F., Ince, C., Longbottom, E. R., Torrance, H. D., Owen, H. C., Hinds, C. J., Pearse, R. M., O’Dywer, M. J., Trogrlic, Z., van der Jagt, M., Lingsma, H., Ponssen, H. H., Schoonderbeek, J. F., Schreiner, F., Verbrugge, S. J., Duran, S., van Achterberg, T., Bakker, J., Gommers, D. A. M. P. J., Ista, E., Krajčová, A., Waldauf, P., Duška, F., Shah, A., Roy, N., McKechnie, S., Doree, C., Fisher, S., Stanworth, S. J., Jensen, J. F., Overgaard, D., Bestle, M. H., Christensen, D. F., Egerod, I., Pivkina, A., Gusarov, V., Zhivotneva, I., Pasko, N., Zamyatin, M., Jensen, J. F., Egerod, I., Bestle, M. H., Christensen, D. F., Alklit, A., Hansen, R. L., Knudsen, H., Grode, L. B., Overgaard, D., Hravnak, M., Chen, L., Dubrawski, A., Clermont, G., Pinsky, M. R., Parry, S. M., Knight, L. D., Connolly, B. C., Baldwin, C. E., Puthucheary, Z. A., Denehy, L., Hart, N., Morris, P. E., Mortimore, J., Granger, C. L., Jensen, H. I., Piers, R., Van den Bulcke, B., Malmgren, J., Metaxa, V., Reyners, A. K., Darmon, M., Rusinova, K., Talmor, D., Meert, A. P., Cancelliere, L., Zubek, L., Maia, P., Michalsen, A., Decruyenaere, J., Kompanje, E., Vanheule, S., Azoulay, E., Vansteelandt, S., Benoit, D., Van den Bulcke, B., Piers, R., Jensen, H. I., Malmgren, J., Metaxa, V., Reyners, A. K., Darmon, M., Rusinova, K., Talmor, D., Meert, A. P., Cancelliere, L., Zubek, L., Maia, P., Michalsen, A., Decruyenaere, J., Kompanje, E., Vanheule, S., Azoulay, E., Vansteelandt, S., Benoit, D., Ryan, C., Dawson, D., Ball, J., Noone, K., Aisling, B., Prudden, S., Ntantana, A., Matamis, D., Savvidou, S., Giannakou, M., Gouva, M., Nakos, G., Koulouras, V., Aron, J., Lumley, G., Milliken, D., Dhadwal, K., McGrath, B. A., Lynch, S. J., Bovento, B., Sharpe, G., Grainger, E., Pieri-Davies, S., Wallace, S., McGrath, B., Lynch, S. J., Bovento, B., Grainger, E., Pieri-Davies, S., Sharpe, G., Wallace, S., Jung, M., Cho, J., Park, H., Suh, G., Kousha, O., Paddle, J., Gripenberg, L. Gamrin, Rehal, M. Sundström, Wernerman, J., Rooyackers, O., de Grooth, H. J., Choo, W. P., Spoelstra-de Man, A. M., Swart, E. L., Oudemans-van Straaten, H. M., Talan, L., Güven, G., Altıntas, N. D., Padar, M., Uusvel, G., Starkopf, L., Starkopf, J., Blaser, A. Reintam, Kalaiselvan, M. S., Arunkumar, A. S., Renuka, M. K., Shivkumar, R. L., Volbeda, M., ten Kate, D., Hoekstra, M., van der Maaten, J. M., Nijsten, M. W., Komaromi, A., Rooyackers, O., Wernerman, J., Norberg, Å., Smedberg, M., Mori, M., Pettersson, L., Norberg, Å., Rooyackers, O., Wernerman, J., Theodorakopoulou, M., Christodoulopoulou, T., Diamantakis, A., Frantzeskaki, F., Kontogiorgi, M., Chrysanthopoulou, E., Lygnos, M., Diakaki, C., Armaganidis, A., Gundogan, K., Dogan, E., Coskun, R., Muhtaroglu, S., Sungur, M., Ziegler, T., Guven, M., Kleyman, A., Khaliq, W., Andreas, D., Singer, M., Meierhans, R., Schuepbach, R., De Brito-Ashurst, I., Zand, F., Sabetian, G., Nikandish, R., Hagar, F., Masjedi, M., Maghsudi, B., Vazin, A., Ghorbani, M., Asadpour, E., Kao, K. C., Chiu, L. C., Hung, C. Y., Chang, C. H., Li, S. H., Hu, H. C., El Maraghi, S., Ali, M., Rageb, D., Helmy, M., Marin-Corral, J., Vilà, C., Masclans, J. R., Vàzquez, A., Martín-Loeches, I., Díaz, E., Yébenes, J. C., Rodriguez, A., Álvarez-Lerma, F., Varga, N., Cortina-Gutiérrez, A., Dono, L., Martínez-Martínez, M., Maldonado, C., Papiol, E., Pérez-Carrasco, M., Ferrer, R., Nweze, K., Morton, B., Welters, I., Houard, M., Voisin, B., Ledoux, G., Six, S., Jaillette, E., Nseir, S., Romdhani, S., Bouneb, R., Loghmari, D., Aicha, N. Ben, Ayachi, J., Meddeb, K., Chouchène, I., Khedher, A., Boussarsar, M., Chan, K. S., Yu, W. L., Marin-Corral, J., Vilà, C., Masclans, J. R., Nolla, J., Vidaur, L., Bonastre, J., Suberbiola, B., Guerrero, J. E., Rodriguez, A., Coll, N. Ramon, Jiménez, G. Jiménez, Brugger, S. Carvalho, Calero, J. Codina, Garrido, B. Balsera, García, M., Martínez, M. Palomar, Vidal, M. Vallverdú, de la Torre, M. C., Vendrell, E., Palomera, E., Güell, E., Yébenes, J. C., Serra-Prat, M., Bermejo-Martín, J. F., Almirall, J., Tomas, E., Escoval, A., Froe, F., Pereira, M. H. Vitoria, Velez, N., Viegas, E., Filipe, E., Groves, C., Reay, M., Chiu, L. C., Hu, H. C., Hung, C. Y., Chang, C. H., Li, S. H., Kao, K. C., Ballin, A., Facchin, F., Sartori, G., Zarantonello, F., Campello, E., Radu, C. M., Rossi, S., Ori, C., Simioni, P., Umei, N., Shingo, I., Santos, A. C., Candeias, C., Moniz, I., Marçal, R., e Silva, Z. Costa, Ribeiro, J. M., Georger, J. F., Ponthus, J. P., Tchir, M., Amilien, V., Ayoub, M., Barsam, E., Martucci, G., Panarello, G., Tuzzolino, F., Capitanio, G., Ferrazza, V., Carollo, T., Giovanni, L., Arcadipane, A., Sánchez, M. López, González-Gay, M. A., Díaz, F. J. Llorca, López, M. I. Rubio, Zogheib, E., Villeret, L., Nader, J., Bernasinski, M., Besserve, P., Caus, T., Dupont, H., Morimont, P., Habran, S., Hubert, R., Desaive, T., Blaffart, F., Janssen, N., Guiot, J., Pironet, A., Dauby, P., Lambermont, B., Zarantonello, F., Ballin, A., Facchin, F., Sartori, G., Campello, E., Pettenuzzo, T., Citton, G., Rossi, S., Simioni, P., Ori, C., Kirakli, C., Ediboglu, O., Ataman, S., Yarici, M., Tuksavul, F., Keating, S., Gibson, A., Gilles, M., Dunn, M., Price, G., Young, N., Remeta, P., Bishop, P., Zamora, M. D. Fernández, Muñoz-Bono, J., Curiel-Balsera, E., Aguilar-Alonso, E., Hinojosa, R., Gordillo-Brenes, A., Arboleda-Sánchez, J. A., Skorniakov, I., Vikulova, D., Whiteley, C., Shaikh, O., Jones, A., Ostermann, M., Forni, L., Scott, M., Sahatjian, J., Linde-Zwirble, W., Hansell, D., Laoveeravat, P., Srisawat, N., Kongwibulwut, M., Peerapornrattana, S., Suwachittanont, N., Wirotwan, T. O., Chatkaew, P., Saeyub, P., Latthaprecha, K., Tiranathanagul, K., Eiam-ong, S., Kellum, J. A., Berthelsen, R. E., Perner, A., Jensen, A. E. K., Jensen, J. U., Bestle, M. H., Gebhard, D. J., Price, J., Kennedy, C. E., Akcan-Arikan, A., Liberatore, A. M. A., Souza, R. B., Martins, A. M. C. R. P. F., Vieira, J. C. F., Kang, Y. R., Nakamae, M. N., Koh, I. H. J., Hamed, K., Khaled, M. M., Soliman, R. Aly, Mokhtar, M. Sherif, Seller-Pérez, G., Arias-Verdú, D., Llopar-Valdor, E., De-Diós-Chacón, I., Quesada-García, G., Herrera-Gutierrez, M. E., Hafes, R., Carroll, G., Doherty, P., Wright, C., Vera, I. G. Guerra, Ralston, M., Gemmell, M. L., MacKay, A., Black, E., Wright, C., Docking, R. I., Appleton, R., Ralston, M. R., Gemmell, L., Appleton, R., Wright, C., Docking, R. I., Black, E., Mackay, A., Rozemeijer, S., Mulier, J. L. G. Haitsma, Röttgering, J. G., Elbers, P. W. G., Spoelstra-de Man, A. M. E., Tuinman, P. R., de Waard, M. C., Oudemans-van Straaten, H. M., Mejeni, N., Nsiala, J., Kilembe, A., Akilimali, P., Thomas, G., Egerod, I., Andersson, A. E., Fagerdahl, A. M., Knudsen, V., Meddeb, K., Cheikh, A. Ben, Hamdaoui, Y., Ayachi, J., Guiga, A., Fraj, N., Romdhani, S., Sma, N., Bouneb, R., Chouchene, I., Khedher, A., Bouafia, N., Boussarsar, M., Amirian, A., Ziaian, B., Masjedi, M., Fleischmann, C., Thomas-Rueddel, D. O., Schettler, A., Schwarzkopf, D., Stacke, A., Reinhart, K., Filipe, E., Escoval, A., Martins, A., Sousa, P., Velez, N., Viegas, E., Tomas, E., Snell, G., Matsa, R., Paary, T. T. S., Kalaiselvan, M. S., Cavalheiro, A. M., Rocha, L. L., Vallone, C. S., Tonilo, A., Lobato, M. D. S., Malheiro, D. T., Sussumo, G., Lucino, N. M., Zand, F., Rosenthal, V. D., Masjedi, M., Sabetian, G., Maghsudi, B., Ghorbani, M., Dashti, A. Sanaei, Yousefipour, A., Goodall, J. R., Williamson, M., Tant, E., Thomas, N., Balci, C., Gonen, C., Haftacı, E., Gurarda, H., Karaca, E., Paldusová, B., Zýková, I., Šímová, D., Houston, S., D’Antona, L., Lloyd, J., Garnelo-Rey, V., Sosic, M., Sotosek-Tokmazic, V., Kuharic, J., Antoncic, I., Dunatov, S., Sustic, A., Chong, C. T., Sim, M., Lyovarin, T., Díaz, F. M. Acosta, Galdó, S. Narbona, Garach, M. Muñoz, Romero, O. Moreno, Bailón, A. M. Pérez, Pinel, A. Carranza, Colmenero, M., Gritsan, A., Gazenkampf, A., Korchagin, E., Dovbish, N., Lee, R. M., Lim, M. P. P., Chong, C. T., Lim, B. C. L., See, J. J., Assis, R., Filipe, F., Lopes, N., Pessoa, L., Pereira, T., Catorze, N., Aydogan, M. S., Aldasoro, C., Marchio, P., Jorda, A., Mauricio, M. D., Guerra-Ojeda, S., Gimeno-Raga, M., Colque-Cano, M., Bertomeu-Artecero, A., Aldasoro, M., Valles, S. L., Tonon, D., Triglia, T., Martin, J. C., Alessi, M. C., Bruder, N., Garrigue, P., Velly, L., Spina, S., Scaravilli, V., Marzorati, C., Colombo, E., Savo, D., Vargiolu, A., Cavenaghi, G., Citerio, G., Andrade, A. H. V., Bulgarelli, P., Araujo, J. A. P., Gonzalez, V., Souza, V. A., Costa, A., Massant, C., Filho, C. A. C. Abreu, Morbeck, R. A., Burgo, L. E., van Groenendael, R., van Eijk, L. T., Leijte, G. P., Koeneman, B., Kox, M., Pickkers, P., García-de la Torre, A., de la Torre-Prados, M., Fernández-Porcel, A., Rueda-Molina, C., Nuevo-Ortega, P., Tsvetanova-Spasova, T., Cámara-Sola, E., García-Alcántara, A., Salido-Díaz, L., Liao, X., Feng, T., Zhang, J., Cao, X., Wu, Q., Xie, Z., Li, H., Kang, Y., Winkler, M. S., Nierhaus, A., Mudersbach, E., Bauer, A., Robbe, L., Zahrte, C., Schwedhelm, E., Kluge, S., Zöllner, C., Morton, B., Mitsi, E., Pennington, S. H., Reine, J., Wright, A. D., Parker, R., Welters, I. D., Blakey, J. D., Rajam, G., Ades, E. W., Ferreira, D. M., Wang, D., Kadioglu, A., Gordon, S. 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Bermejo, Mudarra-Reche, C., Xu, W., Chico-Fernández, M., Montejo-González, J. C., Crewdson, K., Thomas, M., Merghani, M., Fenner, L., Morgan, P., Lockey, D., van Lieshout, E. J., Oomen, B., Binnekade, J. M., Dongelmans, D. A., de Haan, R. J., Juffermans, N. P., Vroom, M. B., Algarte, R., Martínez, L., Sánchez, B., Romero, I., Martínez, F., Quintana, S., Trenado, J., Sheikh, O., Pogson, D., Clinton, R., Riccio, F., Gemmell, L., MacKay, A., Arthur, A., Young, L., Sinclair, A., Markopoulou, D., Venetsanou, K., Filippou, L., Salla, E., Stratouli, S., Alamanos, I., Guirgis, A. H., Rodriguez, R. Gutiérrez, Lorente, M. J. Furones, Guarasa, I. Macias, Ukere, A., Meisner, S., Greiwe, G., Opitz, B., Benten, D., Nashan, B., Fischer, L., Trepte, C. J. C., Reuter, D. A., Haas, S. A., Behem, C. R., Tavazzi, G., Ana, B., Vazir, A., Gibson, D., Price, S., Masjedi, M., Hadavi, M. R., alam, M. Riahi, Sasani, M. R., Parenti, N., Agrusta, F., Palazzi, C., Pifferi, B., Sganzerla, R., Tagliazucchi, F., Luciani, A., Möller, M., Müller-Engelmann, J., Montag, G., Adams, P., Lange, C., Neuzner, J., Gradaus, R., Wodack, K. H., Thürk, F., Waldmann, A. D., Grässler, M. F., Nishimoto, S., Böhm, S. H., Kaniusas, E., Reuter, D. A., Trepte, C. J., Sigmundsson, T., Öhman, T., Redondo, E., Hallbäck, M., Wallin, M., Sipman, F. Suarez, Oldner, A., Sander, C. Hällsjö, Björne, H., Colinas, L., Hernandez, G., Vicho, R., Serna, M., Cuena, R., Canabal, A., Chaari, A., Hakim, K. Abdel, Etman, M., El Bahr, M., El Sakka, A., Bousselmi, K., Arali, A., Kauts, V., Casey, W. F., Bond, O., De Santis, P., Iesu, E., Franchi, F., Vincent, J. L., Creteur, J., Scolletta, S., Taccone, F. S., Marutyan, Z., Hamidova, L., Shakotko, A., Movsisyan, V., Uysupova, I., Evdokimov, A., Petrikov, S., Gonen, C., Haftacı, E., Balci, C., Calvo, F. J. Redondo, Bejarano, N., Baladron, V., Villazala, R., Redondo, J., Padilla, D., Villarejo, P., Akcan-Arikan, A., Kennedy, C. E., Arzapalo, M. F. Aguilar, Gomez-Gonzalez, C., Mas-Font, S., Puppo-Moreno, A., Herrera-Gutierrez, M., Garcia-Garcia, M., Aldunate-Calvo, S., Plata-Menchaca, E. P., Pérez-Fernández, X. L., Estruch, M., Betbese-Roig, A., Campos, P. Cárdenas, Lora, M. Rojas, Gaibor, N. D. Toapanta, Medina, R. S. Contreras, Sanguino, V. D. Gumucio, Casanova, E. J., Riera, J. Sabater, Kritmetapak, K., Peerapornratana, S., Kittiskulnam, P., Dissayabutra, T., Tiranathanagul, K., Susantithapong, P., Praditpornsilpa, K., Tungsanga, K., Eiam-Ong, S., Srisawat, N., Winkelmann, T., Busch, T., Meixensberger, J., Bercker, S., Cabeza, E. M. Flores, Sánchez, M. Sánchez, Giménez, N. Cáceres, Melón, C. Gutierrez, de Lucas, E. Herrero, Estañ, P. Millán, Bernal, M. Hernández, de Lorenzo y Mateos, A. Garcia, Ergin, B., Guerci, P., Specht, P. A. C., Ince, Y., Ince, C., Balik, M., Zakharchenko, M., Los, F., Brodska, H., de Tymowski, C., Augustin, P., Desmard, M., Montravers, P., Stapel, S. N., de Boer, R., Oudemans, H. M., Hollinger, A., Schweingruber, T., Jockers, F., Dickenmann, M., Siegemund, M., Runciman, N., Ralston, M., Appleton, R., Mauri, T., Alban, L., Turrini, C., Sasso, T., Langer, T., Panigada, M., Taccone, P., Carlesso, E., Marenghi, C., Grasselli, G., Pesenti, A., Wibart, P., Reginault, T., Garcia, M., Barbrel, B., Benard, A., Bader, C., Vargas, F., Bui, H. N., Hilbert, G., Simón, J. M. Serrano, Sánchez, P. Carmona, Ferrón, F. Ruiz, de Acilu, M. García, Marin, J., Antonia, V., Ruano, L., Monica, M., Ferrer, R., Masclans, J. R., Roca, O., Hong, G., Kim, D. H., Kim, Y. S., Park, J. S., Jee, Y. K., xiang, Z. Yu, Jia-xing, W., dan, W. Xiao, long, N. Wen, Yu, W., Yan, Z., Cheng, X., Kobayashi, T., Onodera, Y., Akimoto, R., Sugiura, A., Suzuki, H., Iwabuchi, M., Nakane, M., Kawamae, K., Sanchez, P. Carmona, Rodriguez, M. D. Bautista, Delgado, M. Rodriguez, Sánchez, V. Martínez de Pinillos, Gómez, A. Mula, Simón, J. M. Serrano, Beuret, P., Fortes, C., Lauer, M., Reboul, M., Chakarian, J. C., Fabre, X., Philippon-Jouve, B., Devillez, S., Clerc, M., Rittayamai, N., Sklar, M., Dres, M., Rauseo, M., Campbell, C., West, B., Tullis, D. E., Brochard, L., Onodera, Y., Akimoto, R., Suzuki, H., Okada, M., Nakane, M., Kawamae, K., Ahmad, N., Wood, M., Glossop, A., Lucas, J. Higuera, Ortiz, A. Blandino, Alonso, D. Cabestrero, De Pablo Sánchez, R., González, L. Rey, Costa, R., Spinazzola, G., Pizza, A., Ferrone, G., Rossi, M., Antonelli, M., Conti, G., Ribeiro, H., Alves, J., Sousa, M., Reis, P., Socolovsky, C. S., Cauley, R. P., Frankel, J. E., Beam, A. L., Olaniran, K. O., Gibbons, F. K., Christopher, K. B., Pennington, J., Zolfaghari, P., King, H. S., Kong, H. H. Y., Shum, H. P., Yan, W. W., Kaymak, C., Okumus, N., Sari, A., Erdogdu, B., Aksun, S., Basar, H., Ozcan, A., Ozcan, N., Oztuna, D., Malmgren, J. A., Lundin, S., Torén, K., Eckerström, M., Wallin, A., Waldenström, A. C., Riccio, F. C., Pogson, D., Antonio, A. C. P., Leivas, A. F., Kenji, F., James, E., Morgan, P., Carroll, G., Gemmell, L., MacKay, A., Wright, C., Ballantyne, J., Jonnada, S., Gerrard, C. S., Jones, N., Salciccioli, J. D., Marshall, D. C., Komorowski, M., Hartley, A., Sykes, M. C., Goodson, R., Shalhoub, J., Villanueva, J. R. Fernández, Garda, R. Fernández, Lago, A. M. López, Ruiz, E. Rodríguez, Vaquero, R. Hernández, Rodríguez, C. Galbán, Pérez, E. Varo, Hilasque, C., Oliva, I., Sirgo, G., Martin, M. C., Olona, M., Gilavert, M. C., Bodí, M., Ebm, C., Aggarwal, G., Huddart, S., Quiney, N., Cecconi, M., Fernandes, S. M., Silva, J. Santos, Gouveia, J., Silva, D., Marques, R., Bento, H., Alvarez, A., Silva, Z. Costa, Diaz, D. Díaz, Martínez, M. Villanova, Herrejon, E. Palencia, de la Gandara, A. Martinez, Gonzalo, G., Lopez, M. A., de Gopegui Miguelena, P. Ruíz, Matilla, C. I. Bernal, Chueca, P. Sánchez, Longares, M. D. C. Rodríguez, Abril, R. Ramos, Aguilar, A. L. Ruíz, de Murillas, R. Garrido López, Fernández, R. Fernández, Laborías, P. Morales, Castellanos, M. A. Díaz, Laborías, M. E. Morales, Cho, J., Kim, J., Park, J., Woo, S., West, T., Powell, E., Rimmer, A., Orford, C., Jones, N., Williams, J., Matilla, C. I. Bernal, de Gopegui Miguelena, P. Ruiz, Chueca, P. Sánchez, Abril, R. Ramos, Longares, M. D. C. Rodríguez, Aguilar, A. L. Ruíz, de Murillas, R. Garrido López, Bourne, R. S., Shulman, R., Tomlin, M., Mills, G. H., Borthwick, M., Berry, W., Huertas, D. García, Manzano, F., Villagrán-Ramírez, F., Ruiz-Perea, A., Rodríguez-Mejías, C., Santiago-Ruiz, F., Colmenero-Ruiz, M., König, C., Matt, B., Kortgen, A., Hartog, C. S., Wong, A., Balan, C., Barker, G., Srisawat, N., Peerapornratana, S., Laoveeravat, P., Tachaboon, S., Eiam-ong, S., Paratz, J., Kayambu, G., Boots, R., Arzapalo, M. F. Aguilar, Vlasenko, R., Gromova, E., Loginov, S., Kiselevskiy, M., Dolgikova, Y., Tang, K. B., Chau, C. M., Lam, K. N., Gil, E., Suh, G. Y., Park, C. M., Park, J., Chung, C. R., Lee, C. T., Chao, A., Shih, P. Y., Chang, Y. F., Lai, C. H., Hsu, Y. C., Yeh, Y. C., Cheng, Y. J., Colella, V., Zarrillo, N., D’Amico, M., Forfori, F., Pezza, B., Laddomada, T., Beltramelli, V., Pizzaballa, M. L., Doronzio, A., Balicco, B., Kiers, D., van der Heijden, W., Gerretsen, J., de Mast, Q., el Messaoudi, S., Rongen, G., Gomes, M., Kox, M., Pickkers, P., Riksen, N. P., Kashiwagi, Y., Okada, M., Hayashi, K., Inagaki, Y., Fujita, S., Nakamae, M. N., Kang, Y. R., Souza, R. B., Liberatore, A. M. A., Koh, I. H. J., Blet, A., Sadoune, M., Lemarié, J., Bihry, N., Bern, R., Polidano, E., Merval, R., Launay, J. M., Lévy, B., Samuel, J. L., Mebazaa, A., Hartmann, J., Harm, S., and Weber, V.

Published
2016
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11. Use of WATCH antibiotics prior to presentation to the hospital in rural Burkina Faso

Author

Halidou Tinto, van der Sande Ma, Brecht Ingelbeen, Annie Robert, Berenger Kaboré, Annelies Post, M. Peeters, Janneke A. Cox, de Mast Q, Valia D, Lompo P, I. Karama, Erika Vlieghe, van der Ven A, Villalobos Hr, and Jan Jacobs

Subjects
medicine.medical_specialty, Referral, medicine.drug_class, business.industry, Antibiotics, Diagnostic tools, Rural hospital, Ciprofloxacin, Antibiotic resistance, Emergency medicine, medicine, Ceftriaxone, Presentation (obstetrics), business, medicine.drug
Abstract

BackgroundIn low- and middle-income countries (LMIC), the prevalence of antimicrobial resistance (AMR) is increasing. WHO recommends monitoring antibiotic use, in particular Watch antibiotics, clinical important but at risk of becoming ineffective due to increasing AMR. We investigated antibiotic use at primary care or community-level in rural Burkina Faso.MethodsDuring 2016-2017, patients aged >3 months admitted with severe acute fever to the rural hospital of Nanoro Health District, Burkina Faso, reported antibiotic use in the two weeks prior to consultation or hospitalization, which we analysed using the WHO Access, Watch, Reserve (AWaRe) classification. Most Watch antibiotics, e.g. ceftriaxone, are not recommended at primary health center level, as is also the case for ciprofloxacin in children.ResultsOf 920 participants (63.0% ≤14 years), pre-admission antibiotic use was reported by 363 (39.5%) of whom 58 (16.0%) reported more than one antibiotic. Use was more frequent among health center referrals (231, 54.0%) than among self-referred patients (131, 26.7%, p14 year olds (72, 51.1%) than 0-14 year olds (87, 30.7%) and among referrals (41, 28.1%) compared to self-referred patients (117, 42.2%). Most frequently used Watch antibiotics were ceftriaxone (114, 26.9%) and ciprofloxacin (32, 7.5%). Among antibiotics reported by referral patients, ceftriaxone and ciprofloxacin were respectively recorded 100 (36.1%) and 12 times (4.3%).ConclusionThe frequent use of Watch group antibiotics prior to presentation to the hospital in rural Burkina Faso highlights the need to address primary care, over-the-counter and informal community-level antibiotic use as part of antibiotic stewardship in LMIC, facilitating referral, access to qualified prescribers, or improving diagnostic tools in health centers.

Published
2021

12. Dysregulated Innate and Adaptive Immune Responses Discriminate Disease Severity in COVID-19

Author

Janssen, N.A.F. Grondman, I. de Nooijer, A.H. Boahen, C.K. Koeken, V.A.C.M. Matzaraki, V. Kumar, V. He, X. Kox, M. Koenen, H.J.P.M. Smeets, R.L. Joosten, I. Brüggemann, R.J.M. Kouijzer, I.J.E. van der Hoeven, H.G. Schouten, J.A. Frenzel, T. Reijers, M.H.E. Hoefsloot, W. Dofferhoff, A.S.M. van Apeldoorn, M.J. Blaauw, M.J.T. Veerman, K. Maas, C. Schoneveld, A.H. Hoefer, I.E. Derde, L.P.G. van Deuren, M. van der Meer, J.W.M. van Crevel, R. Giamarellos-Bourboulis, E.J. Joosten, L.A.B. van den Heuvel, M.M. Hoogerwerf, J. de Mast, Q. Pickkers, P. Netea, M.G. van de Veerdonk, F.L.

Abstract

The clinical spectrum of COVID-19 varies and the differences in host response characterizing this variation have not been fully elucidated. COVID-19 disease severity correlates with an excessive proinflammatory immune response and profound lymphopenia. Inflammatory responses according to disease severity were explored by plasma cytokine measurements and proteomics analysis in 147 COVID-19 patients. Furthermore, peripheral blood mononuclear cell cytokine production assays and whole blood flow cytometry were performed. Results confirm a hyperinflammatory innate immune state, while highlighting hepatocyte growth factor and stem cell factor as potential biomarkers for disease severity. Clustering analysis revealed no specific inflammatory endotypes in COVID-19 patients. Functional assays revealed abrogated adaptive cytokine production (interferon-γ, interleukin-17, and interleukin-22) and prominent T-cell exhaustion in critically ill patients, whereas innate immune responses were intact or hyperresponsive. Collectively, this extensive analysis provides a comprehensive insight into the pathobiology of severe to critical COVID-19 and highlights potential biomarkers of disease severity. © The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Published
2021

13. Complement Activation in the Disease Course of Coronavirus Disease 2019 and Its Effects on Clinical Outcomes

Author

De Nooijer, A.H. Grondman, I. Janssen, N.A.F. Netea, M.G. Willems, L. Van De Veerdonk, F.L. Giamarellos-Bourboulis, E.J. Toonen, E.J.M. Joosten, L.A.B. Jaeger, M. Dijkstra, H. Lemmers, H. Van Emst, L. Schraa, K. Jacobs, C. Hijmans, A. Jansen, T. Weren, F. Fransman, L. Gerretsen, J. Van De Maat, J. Nijman, G. Moorlag, S. Taks, E. Debisarun, P. Kouijzer, I. Wertheim, H. Hopman, J. Rahamat-Langendoen, J. Bleeker-Rovers, C. Ten Oever, J. Van Crevel, R. Hoogerwerf, J. De Mast, Q. Van Der Hoeven, H. Pickkers, P. Kox, M. Frenzel, T. Schouten, J. Hemelaar, P. Beunders, R. Van Der Velde, S. Kooistra, E. Waalders, N. Claassen, W. Heesakkers, H. Van Schaik, T. Van Der Eng, H. Rovers, N. Klop-Riehl, M.

Abstract

Background: Excessive activation of immune responses in coronavirus disease 2019 (COVID-19) is considered to be related to disease severity, complications, and mortality rate. The complement system is an important component of innate immunity and can stimulate inflammation, but its role in COVID-19 is unknown. Methods: A prospective, longitudinal, single center study was performed in hospitalized patients with COVID-19. Plasma concentrations of complement factors C3a, C3c, and terminal complement complex (TCC) were assessed at baseline and during hospital admission. In parallel, routine laboratory and clinical parameters were collected from medical files and analyzed. Results: Complement factors C3a, C3c, and TCC were significantly increased in plasma of patients with COVID-19 compared with healthy controls (P

Published
2021

14. Chloroquine for treatment of COVID-19 results in subtherapeutic exposure and prolonged QTc intervals

Author

Brüggemann, R.J., primary, Moes, D.J.A.R., additional, van Rhee, K.P., additional, van 't Veer, N.E., additional, Koch, B.C.P., additional, van Rossum, M., additional, Windsant - van den Tweel, A. Vermeulen, additional, Reijers, M.H.E., additional, van Kimmenade, R.R.J., additional, Rahamat-Langedoen, J.C., additional, Rettig, T.C.D., additional, van Raalte, R., additional, van Paassen, J., additional, Polderman, F.N., additional, van der Linden, P.D., additional, Frenzel, T., additional, de Mast, Q., additional, Burger, D.M., additional, Schouten, J., additional, van de Veerdonk, F.L., additional, Pickkers, P., additional, and ter Heine, R., additional

Published
2021
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16. Favorable Anakinra Responses in Severe Covid-19 Patients with Secondary Hemophagocytic Lymphohistiocytosis

Author

Dimopoulos, G. de Mast, Q. Markou, N. Theodorakopoulou, M. Komnos, A. Mouktaroudi, M. Netea, M.G. Spyridopoulos, T. Verheggen, R.J. Hoogerwerf, J. Lachana, A. van de Veerdonk, F.L. Giamarellos-Bourboulis, E.J.

Abstract

Complex immune dysregulation in severe COVID-19 suggests the use of immunomodulation therapies. Dimopoulos et al. describe eight cases of COVID-19 patients who all had secondary hemophagocytic lymphohistiocytosis and showed favorable responses in respiratory function upon treatment with the interleukin-1 receptor antagonist Anakinra. © 2020 Elsevier Inc. Dysregulation of inflammation is hypothesized to play a crucial role in the severe complications of COVID-19, with the IL-1/IL-6 pathway being central. Here, we report on the treatment of eight severe COVID-19 pneumonia patients—seven hospitalized in intensive care units (ICUs) in Greece and one non-ICU patient in the Netherlands—with the interleukin-1 receptor antagonist Anakinra. All patients scored positive for the hemophagocytosis score (HScore) and were diagnosed with secondary hemophagocytic lymphohistocytosis (sHLH) characterized by pancytopenia, hyper-coagulation, acute kidney injury, and hepatobiliary dysfunction. At the end of treatment, ICU patients had less need for vasopressors, significantly improved respiratory function, and lower HScore. Although three patients died, the mortality was lower than historical series of patients with sHLH in sepsis. These data suggest that administration of Anakinra may be beneficial for treating severe COVID-19 patients with sHLH as determined by the HScore, and they support the need for larger clinical studies to validate this concept. © 2020 Elsevier Inc.

Published
2020

18. Perinatal exposure of rats to the HIV drug efavirenz affects medial prefrontal cortex cytoarchitecture

Author

Garcia, L.P., primary, Van de Wijer, L., additional, Hanswijk, S.I., additional, Rando, J., additional, Witteveen, J.S., additional, Middelman, A., additional, ter Heine, R., additional, de Mast, Q., additional, Martens, G.J.M., additional, van der Ven, A.J.A.M., additional, Schellekens, A.F.A., additional, Homberg, J.R., additional, and Kolk, S.M., additional

Published
2020
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19. Chloroquine for treatment of COVID-19 - a pig in a poke?

Author

Brüggemann, R.J., primary, Moes, D.J.A.R., additional, van Rhee, K.P., additional, van ’t Veer, N.E., additional, Koch, B.C.P., additional, van Rossum, M., additional, den Tweel, A. Vermeulen Windsant - van, additional, Reijers, M.H.E., additional, van Kimmenade, R.R.J., additional, Rahamat- Langedoen, J.C., additional, Rettig, T.C.D., additional, van Raalte, R., additional, van Paassen, J., additional, Polderman, F.N., additional, van der Linden, P.D., additional, Frenzel, T., additional, de Mast, Q., additional, Burger, D.M., additional, Schouten, J., additional, van de Veerdonk, F.L., additional, Pickkers, P., additional, and ter Heine, R., additional

Published
2020
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22. [Splenomegaly in an Eritrean refugee: the hyper-reactive malaria splenomegaly syndrome.]

Author

Mm, Cruijsen, Isaie Reuling, Keuter M, Rw, Sauerwein, Aj, Ven, and de Mast Q

Subjects
Adult, Male, Refugees, Splenomegaly, Humans, Syndrome, Eritrea, Hepatomegaly, Malaria, Netherlands
Abstract

Hyper-reactive malaria splenomegaly (HMS) is a rare and potentially severe complication of malaria. It is likely that the incidence of patients with HMS will rise in the Netherlands due to the recent increase in asylum-seekers from Sub-Saharan Africa. It can be difficult to diagnose this disease, as this case shows.A 31-year-old male from Eritrea was admitted with fever and dyspnea, caused by an influenza A-infection. The patient also presented with cachexia, pronounced hepatosplenomegaly and pancytopenia. Microscopic diagnostic analysis for malaria was negative. HMS was eventually diagnosed through high-sensitivity qPCR for malaria, which showed the presence of a very low level of Plasmodium falciparum parasitemia; furthermore, IgM levels were high and malaria serology was strongly positive.HMS should be considered in patients from malaria-endemic areas presenting with splenomegaly and pancytopenia. Because standard diagnostics for malaria are often negative in this population, malaria serology and sensitive qPCR play an important diagnostic role.

Published
2016

31. Anemia and iron homeostasis in a cohort of HIV-infected patients in Indonesia

Author

Jusuf Hadi, Zwitser Aleta, Indrati Agnes R, Sumantri Rachmat, Wisaksana Rudi, de Mast Quirijn, van Crevel Reinout, and van der Ven Andre

Subjects
anemia, iron, HIV, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Anemia is a common clinical finding in HIV-infected patients and iron deficiency or redistribution may contribute to the development of low hemoglobin levels. Iron overload is associated with a poor prognosis in HIV and Hepatitis C virus infections. Iron redistribution may be caused by inflammation but possibly also by hepatitis C co-infection. We examined the prevalence of anemia and its relation to mortality in a cohort of HIV patients in a setting where injecting drug use (IDU) is a main mode of HIV transmission, and measured serum ferritin and sTfR, in relation to anemia, inflammation, stage of HIV disease, ART and HCV infection. Methods Patient characteristics, ART history and iron parameters were recorded from adult HIV patients presenting between September 2007 and August 2009 in the referral hospital for West Java, Indonesia. Kaplan-Meier estimates and Cox's regression were used to assess factors affecting survival. Logistic regression was used to identity parameters associated with high ferritin concentrations. Results Anemia was found in 49.6% of 611 ART-naïve patients, with mild (Hb 10.5 - 12.99 g/dL for men; and 10.5 - 11.99 g/dL for women) anemia in 62.0%, and moderate to severe anemia (Hb < 10.5 g/dL) in 38.0%. Anemia remained an independent factor associated with death, also after adjustment for CD4 count and ART (p = 0.008). Seroprevalence of HCV did not differ in patients with (56.9%) or without anemia (59.6%). Serum ferritin concentrations were elevated, especially in patients with anemia (p = 0.07) and/or low CD4 counts (p < 0.001), and were not related to hsCRP or HCV infection. Soluble TfR concentrations were low and not related to Hb, CD4, hsCRP or ART. Conclusion HIV-associated anemia is common among HIV-infected patients in Indonesia and strongly related to mortality. High ferritin with low sTfR levels suggest that iron redistribution and low erythropoietic activity, rather than iron deficiency, contribute to anemia. Serum ferritin and sTfR should be used cautiously to assess iron status in patients with advanced HIV infection.

Published
2011
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32. Cardiac complication after experimental human malaria infection: a case report

Author

Druilhe Pierre, Stalenhoef Anton, Pop Gheorghe, Wiersma Jorien, Roestenberg Meta, de Mast Quirijn, Nieman An-Emmie, Sauerwein Robert, and van der Ven André

Subjects
Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract

Abstract A 20 year-old healthy female volunteer participated in a clinical Phase I and IIa safety and efficacy trial with candidate malaria vaccine PfLSA-3-rec adjuvanted with aluminium hydroxide. Eleven weeks after the third and last immunization she was experimentally infected by bites of Plasmodium falciparum-infected mosquitoes. When the thick blood smear became positive, at day 11, she was treated with artemether/lumefantrine according to protocol. On day 16 post-infection i.e. two days after completion of treatment, she woke up with retrosternal chest pain. She was diagnosed as acute coronary syndrome and treated accordingly. She recovered quickly and her follow-up was uneventful. Whether the event was related to the study procedures such as the preceding vaccinations, malaria infection or antimalarial drugs remains elusive. However, the relation in time with the experimental malaria infection and apparent absence of an underlying condition makes the infection the most probable trigger. This is in striking contrast, however, with the millions of malaria cases each year and the fact that such complication has never been reported in the literature. The rare occurrence of cardiac events with any of the preceding study procedures may even support a coincidental finding. Apart from acute coronary syndrome, myocarditis can be considered as a final diagnosis, but the true nature and patho-physiological explanation of the event remain unclear.

Published
2009
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33. Prevalence and 3-month follow-up of cerebrovascular MRI markers in hospitalized COVID-19 patients: the CORONIS study.

Author

van Lith TJ, Sluis WM, Wijers NT, Meijer FJA, Ulzen KK, de Bresser J, Dankbaar JW, de Mast Q, Klok FA, Cannegieter SC, Wermer MJH, Huisman MV, Tuladhar AM, van der Worp HB, and de Leeuw FE

Subjects
Humans, Male, Female, Prevalence, Aged, Middle Aged, Hospitalization, Follow-Up Studies, SARS-CoV-2, Cerebrovascular Disorders diagnostic imaging, Cerebrovascular Disorders epidemiology, Cohort Studies, Case-Control Studies, COVID-19 diagnostic imaging, COVID-19 epidemiology, Magnetic Resonance Imaging methods
Abstract

Purpose: To investigate the prevalence of cerebrovascular MRI markers in unselected patients hospitalized for COVID-19 (Coronavirus disease 2019), we compared these with healthy controls without previous SARS-CoV-2 infection or hospitalization and subsequently, investigated longitudinal (incidental) lesions in patients after three months., Methods: CORONIS (CORONavirus and Ischemic Stroke) was an observational cohort study in adult hospitalized patients for COVID-19 and controls without COVID-19, conducted between April 2021 and September 2022. Brain MRI was performed shortly after discharge and after 3 months. Outcomes included recent ischemic (DWI-positive) lesions, previous infarction, microbleeds, white matter hyperintensities (WMH) and intracerebral hemorrhage and were analysed with logistic regression to adjust for confounders., Results: 125 patients with COVID-19 and 47 controls underwent brain MRI a median of 41.5 days after symptom onset. DWI-positive lesions were found in one patient (1%) and in one (2%) control, both clinically silent. WMH were more prevalent in patients (78%) than in controls (62%) (adjusted OR: 2.95 [95% CI: 1.07-8.57]), other cerebrovascular MRI markers did not differ. Prevalence of markers in ICU vs. non-ICU patients was similar. After three months, five patients (5%) had new cerebrovascular lesions, including DWI-positive lesions (1 patient, 1.0%), cerebral infarction (2 patients, 2.0%) and microbleeds (3 patients, 3.1%)., Conclusion: Overall, we found no higher prevalence of cerebrovascular markers in unselected hospitalized COVID-19 patients compared to controls. The few incident DWI-lesions were most likely to be explained by risk-factors of small vessel disease. In the general hospitalized COVID-19 population, COVID-19 shows limited impact on cerebrovascular MRI markers shortly after hospitalization., (© 2024. The Author(s).)

Published
2024
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34. Liver Steatosis is Prevalent in Lean People With HIV and Associated With Exposure to Antiretroviral Treatment-A Cross-sectional Study.

Author

van Eekeren LE, Vadaq N, Vos WAJW, Blaauw MJT, Groenendijk AL, van Lunzen J, Stalenhoef JE, Berrevoets MAH, Verbon A, Weijers G, Netea MG, van der Ven AJAM, de Mast Q, Joosten LAB, and Tjwa ETTL

Abstract

Background: Steatotic liver disease is suggested to have a higher prevalence and severity in people with HIV (PHIV), including in those with a normal body mass index (BMI). In this study, we used data from the 2000HIV cohort to (1) assess the prevalence of liver steatosis and fibrosis in lean versus overweight/obese PHIV and (2) assess associations in these subgroups between steatosis and fibrosis with traditional risk factors and HIV-specific characteristics., Methods: The 2000HIV study cohort comprises 1895 virally suppressed PHIV that were included between 2019 and 2021 in 4 HIV treatment centers in the Netherlands. The majority (58.5%) underwent vibration-controlled transient elastography for the assessment of liver steatosis and fibrosis. The prevalence of steatosis (controlled attenuation parameter ≥263 dB/m) and fibrosis (liver stiffness measurement ≥7.0 kPa) was estimated. Multiple factors including HIV characteristics and antiretroviral drugs were tested in a logistic regression model for association with steatosis and fibrosis. Analyses were performed separately for lean (Asian descent: BMI < 23 kg/m 2 , other descent: BMI < 25 kg/m 2 ) and overweight/obese (other BMI) participants., Results: Of 1050 PHIV including 505 lean and 545 overweight/obese PHIV, liver steatosis was observed in 37.7% of the overall study population, 19.7% of lean, and 54% of overweight/obese PHIV, whereas fibrosis was observed in 9.0% of the overall study population, 5.9% of lean, and 12.0% of overweight/obese PHIV.All associations with fibrosis and most associations with steatosis concerned metabolic factors such as type 2 diabetes mellitus (overall population: adjusted odds ratio [aOR] for steatosis: 2.3 [1.21-4.4], P = .011; aOR for fibrosis: 3.7 [1.82-7.53], P < .001). Furthermore, in lean PLHIV, liver steatosis was associated with CD4 and CD8 counts at enrollment, dual therapy, and history of treatment with raltegravir (aOR: 3.6 [1.53-8.47], P = .003), stavudine (aOR: 3.73 [1.69-8.2], P = .001), and indinavir (aOR: 3.86 [1.59-9.37], P = .003). These associations were not observed in overweight/obese PHIV., Conclusions: Liver steatosis was highly prevalent, affecting approximately one-fifth of lean PHIV and half of overweight/obese PHIV. Fibrosis was observed in a minority. Both steatosis and fibrosis were associated with traditional metabolic risk factors. In addition, (prior) exposure to specific antiretroviral drugs was associated liver steatosis in lean, but not in overweight/obese PHIV. Implementing increased screening protocols could enhance the identification of steatotic liver disease in lean PHIV., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Published
2024
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35. Cardiometabolic Differences in People Living with HIV Receiving Integrase Strand Transfer Inhibitors Compared to Non-nucleoside Reverse Transcriptase Inhibitors: Implications for Current ART Strategies.

Author

Vos WAJW, Vadaq N, Matzaraki V, Otten T, Groenendijk AL, Blaauw MJT, van Eekeren LE, Brinkman K, de Mast Q, Riksen NP, Stalenhoef AFH, van Lunzen J, van der Ven AJAM, Blok WL, and Stalenhoef JE

Subjects
Humans, Male, Female, Middle Aged, Adult, Metabolome drug effects, Anti-HIV Agents therapeutic use, Metabolomics, Cohort Studies, Antiretroviral Therapy, Highly Active, HIV Infections drug therapy, Reverse Transcriptase Inhibitors therapeutic use, HIV Integrase Inhibitors therapeutic use
Abstract

In people living with HIV (PLHIV), integrase strand transfer inhibitors (INSTIs) are part of the first-line combination antiretroviral therapy (cART), while non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens are alternatives. Distinct cART regimens may variably influence the risk for non-AIDS comorbidities. We aimed to compare the metabolome and lipidome of INSTI and NNRTI-based regimens. The 2000HIV study includes asymptomatic PLHIV (n = 1646) on long-term cART, separated into a discovery cohort with 730 INSTI and 617 NNRTI users, and a validation cohort encompassing 209 INSTI and 90 NNRTI users. Baseline plasma samples from INSTI and NNRTI users were compared using mass spectrometry-based untargeted metabolomic (n = 500) analysis. Perturbed metabolic pathways were identified using MetaboAnalyst software. Subsequently, nuclear magnetic resonance spectroscopy was used for targeted lipoprotein and lipid (n = 141) analysis. Metabolome homogeneity was observed between the different types of INSTI and NNRTI. In contrast, higher and lower levels of 59 and 45 metabolites, respectively, were found in the INSTI group compared to NNRTI users, of which 77.9% (81/104) had consistent directionality in the validation cohort. Annotated metabolites belonged mainly to 'lipid and lipid-like molecules', 'organic acids and derivatives' and 'organoheterocyclic compounds'. In pathway analysis, perturbed 'vitamin B1 (thiamin) metabolism', 'de novo fatty acid biosynthesis', 'bile acid biosynthesis' and 'pentose phosphate pathway' were detected, among others. Lipoprotein and lipid levels in NNRTIs were heterogeneous and could not be compared as a group. INSTIs compared to individual NNRTI types showed that HDL cholesterol was lower in INSTIs compared to nevirapine but higher in INSTIs compared to doravirine. In addition, LDL size was lower in INSTIs and nevirapine compared to doravirine. NNRTIs show more heterogeneous cardiometabolic effects than INSTIs, which hampers the comparison between these two classes of drugs. Targeted lipoproteomic and lipid NMR spectroscopy showed that INSTI use was associated with a more unfavorable lipid profile compared to nevirapine, which was shifted to a more favorable profile for INSTI when substituting nevirapine for doravirine, with evidently higher fold changes. The cardiovascular disease risk profile seems more favorable in INSTIs compared to NNRTIs in untargeted metabolomic analysis using mass-spectrometry.

Published
2024
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36. Common and distinct metabolomic markers related to immune aging in Western European and East African populations.

Author

Bulut O, Temba GS, Koeken VACM, Moorlag SJCFM, de Bree LCJ, Mourits VP, Kullaya VI, Jaeger M, Qi C, Riksen NP, Domínguez-Andrés J, Xu CJ, Joosten LAB, Li Y, de Mast Q, and Netea MG

Subjects
Aged, Humans, Cytokines, Immunity, Innate, Metabolome, Aging, East African People, European People
Abstract

In old age, impaired immunity causes high susceptibility to infections and cancer, higher morbidity and mortality, and poorer vaccination efficiency. Many factors, such as genetics, diet, and lifestyle, impact aging. This study aimed to investigate how immune responses change with age in healthy Dutch and Tanzanian individuals and identify common metabolites associated with an aged immune profile. We performed untargeted metabolomics from plasma to identify age-associated metabolites, and we correlated their concentrations with ex-vivo cytokine production by immune cells, DNA methylation-based epigenetic aging, and telomere length. Innate immune responses were impacted differently by age in Dutch and Tanzanian cohorts. Age-related decline in steroid hormone precursors common in both populations was associated with higher systemic inflammation and lower cytokine responses. Hippurate and 2-phenylacetamide, commonly more abundant in older individuals, were negatively correlated with cytokine responses and telomere length and positively correlated with epigenetic aging. Lastly, we identified several metabolites that might contribute to the stronger decline in innate immunity with age in Tanzanians. The shared metabolomic signatures of the two cohorts suggest common mechanisms of immune aging, revealing metabolites with potential contributions. These findings also reflect genetic or environmental effects on circulating metabolites that modulate immune responses., Competing Interests: Declaration of interests M.G.N. is a scientific founder and scientific advisory board member of Trained Therapeutix Discovery (TTxD), and is a scientific founder of Lemba and Biotrip. The other authors declare that they have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Published
2024
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37. Parental engagement in research on paediatric lower respiratory tract infections in Indonesia.

Author

Ciptaningtyas VR, Sumekar TA, de Mast Q, de Jonge MI, and Margawati A

Subjects
Child, Humans, Adolescent, Indonesia, Cross-Sectional Studies, Educational Status, Parents, Respiratory Tract Infections epidemiology
Abstract

Background: Lower respiratory tract infections (LRTIs) in children are a major concern in Indonesia as it is the leading cause of morbidity and mortality. Therefore, research on LRTIs is crucial to improve children's health. However, clinical research in children is challenging due to parental concerns. This study aims to understand parental considerations for taking part in clinical studies on LRTI in the Indonesian context., Methods: A cross-sectional study using a validated online questionnaire was conducted from November 2021 to March 2022. This study included parents from two public elementary schools and two private primary schools in Semarang, Indonesia. A total of 1236 responses were analysed., Results: There was a significant association between educational attainment and willingness to participate in general health and LRTI-related research requiring specimen collection; respondents with an advanced educational level were more likely to refuse participation in research. A similar pattern was observed among respondents with smaller families and younger children against participation in LRTI research. Most respondents who indicated not to participate explained that they did not perceive the necessity to take part and expressed their concerns about endangering their child's health as a consequence of the specimen collection. Most respondents expected a personal benefit and prioritized access to the study results for their child., Conclusion: Parents' educational background and family composition are important determinants of parental engagement in research on LRTI in Indonesia. Notably, parents with a lower educational level, having large families, and older children were more inclined to participate. The emphasis on concerns about potential harm and personal benefit underscores the need for a targeted communication strategy., (© 2024. The Author(s).)

Published
2024
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38. Genetic and nongenetic drivers of platelet reactivity in healthy Tanzanian individuals.

Author

Kullaya VI, Temba GS, Vadaq N, Njau J, Boahen CK, Nkambule BB, Thibord F, Chen MH, Pecht T, Lyamuya F, Kumar V, Netea MG, Mmbaga BT, van der Ven A, Johnson AD, and de Mast Q

Subjects
Adult, Humans, Tanzania, Platelet Activation, Receptor, PAR-1 metabolism, Platelet Aggregation physiology, Blood Platelets metabolism
Abstract

Background: Platelets play a key role in hemostasis, inflammation, and cardiovascular diseases. Platelet reactivity is highly variable between individuals. The drivers of this variability in populations from Sub-Saharan Africa remain largely unknown., Objectives: We aimed to investigate the nongenetic and genetic determinants of platelet reactivity in healthy adults living in a rapidly urbanizing area in Northern Tanzania., Methods: Platelet activation and reactivity were measured by platelet P-selectin expression and the binding of fibrinogen in unstimulated blood and after ex vivo stimulation with adenosine diphosphate and PAR-1 and PAR-4 ligands. We then analyzed the associations of platelet parameters with host genetic and nongenetic factors, environmental factors, plasma inflammatory markers, and plasma metabolites., Results: Only a few associations were found between platelet reactivity parameters and plasma inflammatory markers and nongenetic host and environmental factors. In contrast, untargeted plasma metabolomics revealed a large number of associations with food-derived metabolites, including phytochemicals that were previously reported to inhibit platelet reactivity. Genome-wide single-nucleotide polymorphism genotyping identified 2 novel single-nucleotide polymorphisms (rs903650 and rs4789332) that were associated with platelet reactivity at the genome-wide level (P < 5 × 10 -8 ) as well as a number of variants in the PAR4 gene (F2RL3) that were associated with PAR4-induced reactivity., Conclusion: Our study uncovered factors that determine variation in platelet reactivity in a population in East Africa that is rapidly transitioning to an urban lifestyle, including the importance of genetic ancestry and the gradual abandoning of the traditional East African diet., Competing Interests: Declaration of competing interests There are no competing interests to disclose., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Published
2024
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39. Host genetic regulation of human gut microbial structural variation.

Author

Zhernakova DV, Wang D, Liu L, Andreu-Sánchez S, Zhang Y, Ruiz-Moreno AJ, Peng H, Plomp N, Del Castillo-Izquierdo Á, Gacesa R, Lopera-Maya EA, Temba GS, Kullaya VI, van Leeuwen SS, Xavier RJ, de Mast Q, Joosten LAB, Riksen NP, Rutten JHW, Netea MG, Sanna S, Wijmenga C, Weersma RK, Zhernakova A, Harmsen HJM, and Fu J

Subjects
Humans, Acetylgalactosamine metabolism, Cohort Studies, Computer Simulation, Faecalibacterium prausnitzii genetics, Genome, Human genetics, Genotype, In Vitro Techniques, Multigene Family, Netherlands, Tanzania, Bacteria classification, Bacteria genetics, Bacteria isolation & purification, Gastrointestinal Microbiome genetics, Host Microbial Interactions genetics, Metagenome genetics
Abstract

Although the impact of host genetics on gut microbial diversity and the abundance of specific taxa is well established 1-6 , little is known about how host genetics regulates the genetic diversity of gut microorganisms. Here we conducted a meta-analysis of associations between human genetic variation and gut microbial structural variation in 9,015 individuals from four Dutch cohorts. Strikingly, the presence rate of a structural variation segment in Faecalibacterium prausnitzii that harbours an N-acetylgalactosamine (GalNAc) utilization gene cluster is higher in individuals who secrete the type A oligosaccharide antigen terminating in GalNAc, a feature that is jointly determined by human ABO and FUT2 genotypes, and we could replicate this association in a Tanzanian cohort. In vitro experiments demonstrated that GalNAc can be used as the sole carbohydrate source for F. prausnitzii strains that carry the GalNAc-metabolizing pathway. Further in silico and in vitro studies demonstrated that other ABO-associated species can also utilize GalNAc, particularly Collinsella aerofaciens. The GalNAc utilization genes are also associated with the host's cardiometabolic health, particularly in individuals with mucosal A-antigen. Together, the findings of our study demonstrate that genetic associations across the human genome and bacterial metagenome can provide functional insights into the reciprocal host-microbiome relationship., (© 2024. The Author(s).)

Published
2024
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40. OTULIN Haploinsufficiency-Related Fasciitis and Skin Necrosis Treated by TNF Inhibition.

Author

Arts RJW, van der Linden TJ, van der Made CI, Hendriks MMC, van der Heijden WA, de Mast Q, Schuurs-Hoeijmakers JHM, Simons A, Spaan AN, Mulders-Manders CM, and van de Veerdonk FL

Subjects
Female, Humans, Inflammation genetics, Necrosis, Ubiquitination, Fasciitis, Haploinsufficiency
Abstract

Here, we describe an adult female with severe fasciitis and skin necrosis who carried a private, predicted deleterious missense mutation in OTULIN in heterozygosity. OTULIN is a cellular regulator of deubiquitination that has been shown to play a key role in intrinsic immunity against staphylococcal α-toxin. The patient was treated with broad-spectrum antibiotics, and multiple surgical explorations were conducted without clinical response. Since autoinflammation was the predominant clinical feature, TNF inhibition was started with a good clinical response. We show that excessive inflammation in OTULIN haploinsufficiency can be effectively treated by TNF inhibition., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Published
2023
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41. Differences in the inflammatory proteome of East African and Western European adults and associations with environmental and dietary factors.

Author

Temba GS, Vadaq N, Kullaya V, Pecht T, Lionetti P, Cavalieri D, Schultze JL, Kavishe R, Joosten LAB, van der Ven AJ, Mmbaga BT, Netea MG, and de Mast Q

Subjects
Humans, Africa South of the Sahara epidemiology, Noncommunicable Diseases epidemiology, Proteomics, East African People, Inflammation, Proteome, European People
Abstract

Non-communicable diseases (NCDs) are rising rapidly in urbanizing populations in sub-Saharan Africa. Assessment of inflammatory and metabolic characteristics of a urbanizing African population and the comparison with populations outside Africa could provide insight in the pathophysiology of the rapidly increasing epidemic of NCDs, including the role of environmental and dietary changes. Using a proteomic plasma profiling approach comprising 92 inflammation-related molecules, we examined differences in the inflammatory proteome in healthy Tanzanian and healthy Dutch adults. We show that healthy Tanzanians display a pro-inflammatory phenotype compared to Dutch subjects, with enhanced activity of the Wnt/β-catenin signalling pathway and higher concentrations of different metabolic regulators such as 4E-BP1 and fibroblast growth factor 21. Among the Tanzanian volunteers, food-derived metabolites were identified as an important driver of variation in inflammation-related molecules, emphasizing the potential importance of lifestyle changes. These findings endorse the importance of the current dietary transition and the inclusion of underrepresented populations in systems immunology studies., Competing Interests: GT, NV, VK, TP, PL, DC, JS, RK, LJ, Av, BM, MN, Qd No competing interests declared, (© 2023, Temba et al.)

Published
2023
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42. Gut dysbiosis associates with cytokine production capacity in viral-suppressed people living with HIV.

Author

Zhang Y, Andreu-Sánchez S, Vadaq N, Wang D, Matzaraki V, van der Heijden WA, Gacesa R, Weersma RK, Zhernakova A, Vandekerckhove L, de Mast Q, Joosten LAB, Netea MG, van der Ven AJAM, and Fu J

Subjects
Humans, Interleukin-10, Interleukin-6, Dysbiosis, Cytokines, HIV, HIV Infections drug therapy
Abstract

Background: People living with human immunodeficiency virus (PLHIV) are exposed to chronic immune dysregulation, even when virus replication is suppressed by antiretroviral therapy (ART). Given the emerging role of the gut microbiome in immunity, we hypothesized that the gut microbiome may be related to the cytokine production capacity of PLHIV., Methods: To test this hypothesis, we collected metagenomic data from 143 ART-treated PLHIV and assessed the ex vivo production capacity of eight different cytokines [interleukin-1β (IL-1β), IL-6, IL-1Ra, IL-10, IL-17, IL-22, tumor necrosis factor, and interferon-γ] in response to different stimuli. We also characterized CD4 + T-cell counts, HIV reservoir, and other clinical parameters., Results: Compared with 190 age- and sex-matched controls and a second independent control cohort, PLHIV showed microbial dysbiosis that was correlated with viral reservoir levels (CD4 + T-cell-associated HIV-1 DNA), cytokine production capacity, and sexual behavior. Notably, we identified two genetically different P. copri strains that were enriched in either PLHIV or healthy controls. The control-related strain showed a stronger negative association with cytokine production capacity than the PLHIV-related strain, particularly for Pam3Cys-incuded IL-6 and IL-10 production. The control-related strain is also positively associated with CD4 + T-cell level., Conclusions: Our findings suggest that modulating the gut microbiome may be a strategy to modulate immune response in PLHIV., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Andreu-Sánchez, Vadaq, Wang, Matzaraki, van der Heijden, Gacesa, Weersma, Zhernakova, Vandekerckhove, de Mast, Joosten, Netea, van der Ven and Fu.)

Published
2023
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43. High-throughput proteomic analysis reveals systemic dysregulation in virally suppressed people living with HIV.

Author

Vadaq N, Zhang Y, Vos WA, Groenendijk AL, Blaauw MJ, van Eekeren LE, Jacobs-Cleophas M, van de Wijer L, Dos Santos JC, Gasem MH, Joosten LA, Netea MG, de Mast Q, Fu J, van der Ven AJ, and Matzaraki V

Subjects
Humans, Proteomics, Inflammation complications, C-Reactive Protein, HIV Infections complications, HIV Infections drug therapy, Cardiovascular Diseases
Abstract

BACKGROUNDPeople living with HIV (PLHIV) receiving antiretroviral therapy (ART) exhibit persistent immune dysregulation and microbial dysbiosis, leading to development of cardiovascular diseases (CVDs). We initially compared plasma proteomic profiles between 205 PLHIV and 120 healthy control participants (HCs) and validated the results in an independent cohort of 639 PLHIV and 99 HCs. Differentially expressed proteins (DEPs) were then associated to microbiome data. Finally, we assessed which proteins were linked with CVD development in PLHIV.METHODSProximity extension assay technology was used to measure 1,472 plasma proteins. Markers of systemic inflammation (C-reactive protein, D-dimer, IL-6, soluble CD14, and soluble CD163) and microbial translocation (IFABP) were measured by ELISA, and gut bacterial species were identified using shotgun metagenomic sequencing. Baseline CVD data were available for all PLHIV, and 205 PLHIV were recorded for development of CVD during a 5-year follow-up.RESULTSPLHIV receiving ART had systemic dysregulation of protein concentrations, compared with HCs. Most of the DEPs originated from the intestine and lymphoid tissues and were enriched in immune- and lipid metabolism-related pathways. DEPs originating from the intestine were associated with specific gut bacterial species. Finally, we identified upregulated proteins in PLHIV (GDF15, PLAUR, RELT, NEFL, COL6A3, and EDA2R), unlike most markers of systemic inflammation, associated with the presence and risk of developing CVD during 5-year follow-up.CONCLUSIONOur findings suggest a systemic dysregulation of protein concentrations in PLHIV; some proteins were associated with CVD development. Most DEPs originated from the gut and were related to specific gut bacterial species.TRIAL REGISTRATIONClinicalTrials.gov NCT03994835.FUNDINGAIDS-fonds (P-29001), ViiV healthcare grant (A18-1052), Spinoza Prize (NWO SPI94-212), European Research Council (ERC) Advanced grant (grant 833247), and Indonesia Endowment Fund for Education.

Published
2023
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44. [New infectious diseases in Europe; the effect of climate change, globalisation and human behaviour].

Author

Goorhuis AB, de Mast Q, Hovius JW, and van Nood E

Subjects
Humans, Climate Change, Europe epidemiology, Communicable Diseases epidemiology, Encephalitis, Tick-Borne epidemiology
Abstract

Climate change directly and indirectly contributes to the emergence of vector and water borne infections. Other infectious diseases may be introduced to new geographical areas as a result of globalisation and changing human behaviour. Despite the still low absolute risk, the pathogenicity of some of these infections creates a significant challenge for clinicians. Awareness of changing disease epidemiology helps in timely recognition of such infections. Vaccination guidelines for emerging vaccine-preventable diseases, such as tick-borne encephalitis and leptospirosis, may need to be updated.

Published
2023

45. Abacavir use is associated with increased prothrombin conversion.

Author

Yan Q, Huang S, van der Heijden W, Ninivaggi M, van de Wijer L, de Laat-Kremers R, Van der Ven AJ, de Laat B, and de Mast Q

Subjects
Humans, Thrombin metabolism, von Willebrand Factor, Cross-Sectional Studies, Anticoagulants, Prothrombin, HIV Infections
Abstract

There is ongoing debate as to whether abacavir (ABC) increases the risk for cardiovascular disease(CVD) in people living with HIV (PLHIV) and the mechanisms underlying this possible association. We recently showed that the use of an ABC-containing regimen was independently associated with increased thrombin generation (TG). In the present study, we aim to explore these findings further, by studying the mechanistical processes that underly the global thrombin generation test via thrombin dynamics analysis. Thrombin dynamics analysis can pinpoint the cause of increased thrombin generation associated with ABC-use either to the procoagulant prothrombin conversion pathway or the anticoagulant thrombin inactivation pathway. In this cross-sectional study, 208 virally suppressed PLHIV were included, of whom 94 were on a ABC-containing regimen, 92 on a tenofovir disoproxil fumarate (TDF)-containing regimen, and the remainder on other regimens. We used Calibrated Automated Thrombinography to measure thrombin generation and perform thrombin dynamics analysis. The total amount of prothrombin conversion, as well as the maximum rate of prothrombin conversion were significantly increased in PLHIV on an ABC containing regimen compared to other treatment regimens. The levels of pro- and anticoagulant factors were comparable, indicating that the ABC-induced changes affect the kinetics of prothrombin conversion rather than procoagulant factor levels. Moreover, Von Willebrand Factor (VWF), active VWF and VWF pro-peptide levels were significantly higher in PLHIV than controls without HIV. However, they did not differ between ABC and non-ABC treated participants., Competing Interests: QY, SH, RL-K, MN, and BL are employees of Synapse Research Institute, part of Diagnostica Stago SAS. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yan, Huang, van der Heijden, Ninivaggi, van de Wijer, de Laat-Kremers, Van der Ven, de Laat and de Mast.)

Published
2023
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46. Whole sporozoite immunization with Plasmodium falciparum strain NF135 in a randomized trial.

Author

van der Boor SC, Alkema M, van Gemert GJ, Teelen K, van de Vegte-Bolmer M, Walk J, van Crevel R, de Mast Q, Ockenhouse CF, Sauerwein RW, and McCall MBB

Subjects
Adult, Animals, Humans, Artemether, Lumefantrine Drug Combination therapeutic use, Immunization methods, Plasmodium falciparum, Sporozoites, Antimalarials therapeutic use, Insect Bites and Stings drug therapy, Malaria prevention & control, Malaria Vaccines adverse effects
Abstract

Background: Whole sporozoite immunization under chemoprophylaxis (CPS regime) induces long-lasting sterile homologous protection in the controlled human malaria infection model using Plasmodium falciparum strain NF54. The relative proficiency of liver-stage parasite development may be an important factor determining immunization efficacy. Previous studies show that Plasmodium falciparum strain NF135 produces relatively high numbers of large liver-stage schizonts in vitro. Here, we evaluate this strain for use in CPS immunization regimes., Methods: In a partially randomized, open-label study conducted at the Radboudumc, Nijmegen, the Netherlands, healthy, malaria-naïve adults were immunized by three rounds of fifteen or five NF135-infected mosquito bites under mefloquine prophylaxis (cohort A) or fifteen NF135-infected mosquito bites and presumptive treatment with artemether/lumefantrine (cohort B). Cohort A participants were exposed to a homologous challenge 19 weeks after immunization. The primary objective of the study was to evaluate the safety and tolerability of CPS immunizations with NF135., Results: Relatively high liver-to-blood inocula were observed during immunization with NF135 in both cohorts. Eighteen of 30 (60%) high-dose participants and 3/10 (30%) low-dose participants experienced grade 3 adverse events 7 to 21 days following their first immunization. All cohort A participants and two participants in cohort B developed breakthrough blood-stage malaria infections during immunizations requiring rescue treatment. The resulting compromised immunizations induced modest sterile protection against homologous challenge in cohort A (5/17; 29%)., Conclusions: These CPS regimes using NF135 were relatively poorly tolerated and frequently required rescue treatment, thereby compromising immunization efficiency and protective efficacy. Consequently, the full potential of NF135 sporozoites for induction of immune protection remains inconclusive. Nonetheless, the high liver-stage burden achieved by this strain highlights it as an interesting potential candidate for novel whole sporozoite immunization approaches., Trial Registration: The trial was registered at ClinicalTrials.gov under identifier NCT03813108., (© 2023. The Author(s).)

Published
2023
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47. A difficult to treat Leishmania infantum relapse after allogeneic stem cell transplantation.

Author

Arts RJW, Ector GICG, Bosch-Nicolau P, Molina I, McCall MBB, van der Velden WJFM, van Laarhoven A, de Mast Q, and van Dorp S

Abstract

Here we describe a complicated case of a relapsed Leishmania infantum infection after an allogeneic stem cell transplantation (allo-SCT) for primary myelofibrosis. Three years earlier the patient had been diagnosed with a hemophagocytic lymphohistiocytosis secondary to a visceral Leishmania infantum infection, for which he was effectively treated with a cumulative dose of 40 mg/kg liposomal amphotericin B. During the first disease episode he was also diagnosed with primary myelofibrosis for which he received medical follow-up. One year later ruxolitinib was started due to progressive disease. No Leishmania relapse occurred. Nevertheless, the marrow fibrosis progressed, and an allo-SCT was performed. Two months after allo-SCT prolonged fever and a persistent pancytopenia occurred, which was due to a relapse of visceral Leishmaniasis. The infection was refractory to a prolonged treatment with liposomal amphotericin B with a cumulative dose up to 100 mg/kg. Salvage treatment with miltefosine led to reduction of fever within a few days and was followed by a slow recovery of pancytopenia over the following months. The Leishmania parasite load by PCR started to decline and after 3.5 months no Leishmania DNA could be detected anymore and follow-up until ten months afterwards did not show a relapse., Competing Interests: None., (© 2023 The Authors.)

Published
2023
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48. Targeted plasma proteomics identifies MICA and IL1R1 proteins associated with HIV-1 reservoir size.

Author

Blaauw MJT, Cristina Dos Santos J, Vadaq N, Trypsteen W, van der Heijden W, Groenendijk A, Zhang Z, Li Y, de Mast Q, Netea MG, Joosten LAB, Vandekerckhove L, van der Ven A, and Matzaraki V

Abstract

HIV-1 reservoir shows high variability in size and activity among virally suppressed individuals. Differences in the size of the viral reservoir may relate to differences in plasma protein concentrations. We tested whether plasma protein expression levels are associated with levels of cell-associated (CA) HIV-1 DNA and RNA in 211 virally suppressed people living with HIV (PLHIV). Plasma concentrations of FOLR1, IL1R1, MICA, and FETUB showed a positive association with CA HIV-1 RNA and DNA. Moreover, SNPs in close proximity to IL1R1 and MICA genes were found to influence the levels of CA HIV-1 RNA and DNA. We found a difference in mRNA expression of the MICA gene in homozygotes carrying the rs9348866-A allele compared to the ones carrying the G allele (p < 0.005). Overall, our findings pinpoint plasma proteins that could serve as potential targets for therapeutic interventions to lower or even eradicate cells containing CA HIV-1 RNA and DNA in PLHIV., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

Published
2023
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49. Correction: Immunogenicity and reactogenicity of SARS-CoV-2 vaccines in people living with HIV in the Netherlands: A nationwide prospective cohort study.

Author

Hensley KS, Jongkees MJ, Geers D, GeurtsvanKessel CH, Mueller YM, Dalm VASH, Papageorgiou G, Steggink H, Gorska A, Bogers S, den Hollander JG, Bierman WFW, Gelinck LBS, Schippers EF, Ammerlaan HSM, van der Valk M, van Vonderen MGA, Delsing CE, Gisolf EH, Bruns AHW, Lauw FN, Berrevoets MAH, Sigaloff KCE, Soetekouw R, Branger J, de Mast Q, Lammers AJJ, Lowe SH, de Vries RD, Katsikis PD, Rijnders BJA, Brinkman K, Roukens AHE, and Rokx C

Abstract

[This corrects the article DOI: 10.1371/journal.pmed.1003979.]., (Copyright: © 2023 Hensley et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Published
2023
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50. Longitudinal proteomic profiling of the inflammatory response in dengue patients.

Author

Garishah FM, Boahen CK, Vadaq N, Pramudo SG, Tunjungputri RN, Riswari SF, van Rij RP, Alisjahbana B, Gasem MH, van der Ven AJAM, and de Mast Q

Subjects
Humans, Interleukin-33, Proteome, Proteomics, Cytokines metabolism, Chemokines, Interleukin-10, Dengue
Abstract

Background: The immunopathogenesis of dengue virus (DENV) infection remains incompletely understood. To increase our understanding of inflammatory response in non-severe dengue, we assessed longitudinal changes in the inflammatory proteome in patients with an acute DENV infection., Methods: Using a multiplex proximity extension assay (PEA), we measured relative levels of 368 inflammatory markers in plasma samples from hospitalized patients with non-severe DENV infection in the acute (n = 43) and convalescence (n = 35) phase of the infection and samples of healthy controls (n = 10)., Results: We identified 203 upregulated and 39 downregulated proteins in acute versus convalescent plasma samples. The upregulated proteins had a strong representation of interferon (IFN) and IFN-inducible effector proteins, cytokines (e.g. IL-10, IL-33) and cytokine receptors, chemokines, pro-apoptotic proteins (e.g. granzymes) and endothelial markers. A number of differentially expressed proteins (DEPs) have not been reported in previous studies. Functional network analysis highlighted a central role for IFNγ, IL-10, IL-33 and chemokines. We identified different novel associations between inflammatory proteins and circulating concentrations of the endothelial glycocalyx disruption surrogate marker syndecan-1. Conclusion: This unbiased proteome analysis provides a comprehensive insight in the inflammatory response in DENV infection and its association with glycocalyx disruption., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Garishah et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Published
2023
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