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2. LPS‐Induced ex vivo Cytokine Production is Not Augmented in Patients with Von Hippel‐Lindau Disease
- Author
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Kiers, D., Timmers, H. J. L. M., Gerretsen, J., Pickkers, P., and Kox, M.
- Published
- 2017
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3. ESICM LIVES 2016: part one: Milan, Italy. 1-5 October 2016
- Author
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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. B., Koch, R., Kox, M., Rahamat-Langedoen, J., Schloesser, J., de Jonge, M., Pickkers, P., Bringue, J., Guillamat-Prats, R., Torrents, E., Martinez, M. L., Camprubí-Rimblas, M., Artigas, A., Blanch, L., Park, S. Y., Park, Y. B., Song, D. K., Shrestha, S., Park, S. H., Koh, Y., Park, M. J., Hong, C. W., Lesur, O., Coquerel, D., Sainsily, X., Cote, J., Söllradl, T., Murza, A., Dumont, L., Dumaine, R., Grandbois, M., Sarret, P., Marsault, E., Salvail, D., Auger-Messier, M., Chagnon, F., Lauretta, M. P., Greco, E., Dyson, A., Singer, M., Preau, S., Ambler, M., Sigurta, A., Saeed, S., Singer, M., Sarıca, L. Topcu, Zibandeh, N., Genc, D., Gul, F., Akkoc, T., Kombak, E., Cinel, L., Akkoc, T., Cinel, I., Pollen, S. J., Arulkumaran, N., Singer, M., Torrance, H. D., Longbottom, E. R., Warnes, G., Hinds, C. J., Pennington, D. J., Brohi, K., O’Dwyer, M. J., Kim, H. Y., Na, S., Kim, J., Chang, Y. F., Chao, A., Shih, P. Y., Lee, C. T., Yeh, Y. C., Chen, L. W., Adriaanse, M., Trogrlic, Z., Ista, E., Lingsma, H., Rietdijk, W., Ponssen, H. H., Schoonderbeek, J. F., Schreiner, F., Verbrugge, S. J., Duran, S., Gommers, D. A. M. P. J., van der Jagt, M., Funcke, S., Sauerlaender, S., Saugel, B., Pinnschmidt, H., Reuter, D. A., Nitzschke, R., Perbet, S., Biboulet, C., Lenoire, A., Bourdeaux, D., Pereira, B., Plaud, B., Bazin, J. E., Sautou, V., Mebazaa, A., Constantin, J. M., Legrand, M., Boyko, Y., Jennum, P., Nikolic, M., Oerding, H., Holst, R., Toft, P., Nedergaard, H. K., Haberlandt, T., Jensen, H. I., Toft, P., Park, S., Kim, S., Cho, Y. J., Lim, Y. J., Chan, A., Tang, S., Nunes, S. L., Forsberg, S., Blomqvist, H., Berggren, L., Sörberg, M., Sarapohja, T., Wickerts, C. J., Hofhuis, J. G. M., Rose, L., Blackwood, B., Akerman, E., Mcgaughey, J., Egerod, I., Fossum, M., Foss, H., Georgiou, E., Graff, H. J., Kalafati, M., Sperlinga, R., Schafer, A., Wojnicka, A. G., Spronk, P. 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L., Torrini, F., Iaquaniello, C., Bongiovanni, F., Antonelli, M., Toscani, L., Antonakaki, D., Bastoni, D., Aya, H. D., Rhodes, A., Cecconi, M., Jozwiak, M., Depret, F., Teboul, J. L., Alphonsine, J., Lai, C., Richard, C., Monnet, X., László, I., Demeter, G., Öveges, N., Tánczos, K., Németh, M., Trásy, D., Kertmegi, I., Érces, D., Tudor, B., Kaszaki, J., Molnár, Z., Hasanin, A., Lotfy, A., El-adawy, A., Nassar, H., Mahmoud, S., Abougabal, A., Mukhtar, A., Quinty, F., Habchi, S., Luzi, A., Antok, E., Hernandez, G., Lara, B., Enberg, L., Ortega, M., Leon, P., Kripper, C., Aguilera, P., Kattan, E., Bakker, J., Huber, W., Lehmann, M., Sakka, S., Bein, B., Schmid, R. M., Preti, J., Creteur, J., Herpain, A., Marc, J., Zogheib, E., Trojette, F., Bar, S., Kontar, L., Titeca, D., Richecoeur, J., Gelee, B., Verrier, N., Mercier, R., Lorne, E., Maizel, J., Dupont, H., Slama, M., Abdelfattah, M. E., Eladawy, A., Elsayed, M. A. Ali, Mukhtar, A., Montenegro, A. Pedraza, Zepeda, E. 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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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4. Systemic inflammation down-regulates glyoxalase-1 expression: an experimental study in healthy males
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Driessen, Rob G.H., Kiers, D., Schalkwijk, Casper G., Scheijen, Jean L.J.M., Gerretsen, J.J.F., Pickkers, P., Kox, M., Bussel, Bas C.T. van, Driessen, Rob G.H., Kiers, D., Schalkwijk, Casper G., Scheijen, Jean L.J.M., Gerretsen, J.J.F., Pickkers, P., Kox, M., and Bussel, Bas C.T. van
- Abstract
Contains fulltext : 238470.pdf (Publisher’s version ) (Open Access)
- Published
- 2021
5. Systemic inflammation down-regulates glyoxalase-1 expression: an experimental study in healthy males
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Driessen, R.G.H., Kiers, D., Schalkwijk, Casper G., Scheijen, Jean L.J.M., Gerretsen, J.J.F., Pickkers, P., Kox, M., Bussel, Bas C.T. van, Driessen, R.G.H., Kiers, D., Schalkwijk, Casper G., Scheijen, Jean L.J.M., Gerretsen, J.J.F., Pickkers, P., Kox, M., and Bussel, Bas C.T. van
- Abstract
Contains fulltext : 238470.pdf (Publisher’s version ) (Open Access)
- Published
- 2021
6. Hypoxia and hypoxia-mimetics attenuate the inflammatory response during murine endotoxemia
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Kiers, D, Groeneveld, R, van der Hoeven, JG, Scheffer, GJ, Pickkers, P, and Kox, M
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- 2015
- Full Text
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7. 0900. Effects of oxygen status on the innate immune response in humans in vivo
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Kiers, D, John, A, Janssen, E, Scheffer, GJ, van der Hoeven, H, Pickkers, P, and Kox, M
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- 2014
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8. Hypoxia attenuates inflammation-induced hepcidin synthesis during experimental human endotoxemia
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Kiers, D., Eijk, L.T.G.J. van, Hoeven, J.G. van der, Swinkels, D.W., Pickkers, P., Kox, M., Kiers, D., Eijk, L.T.G.J. van, Hoeven, J.G. van der, Swinkels, D.W., Pickkers, P., and Kox, M.
- Abstract
Contains fulltext : 205269.pdf (publisher's version ) (Open Access)
- Published
- 2019
9. Treatment With Acetylsalicylic Acid Reverses Endotoxin Tolerance in Humans In Vivo: A Randomized Placebo-Controlled Study
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Leijte, G.P., Kiers, D., Heijden, W.A. van der, Jansen, A., Gerretsen, J., Boerrigter, V., Netea, M.G., Kox, M., Pickkers, P., Leijte, G.P., Kiers, D., Heijden, W.A. van der, Jansen, A., Gerretsen, J., Boerrigter, V., Netea, M.G., Kox, M., and Pickkers, P.
- Abstract
Contains fulltext : 202958.pdf (publisher's version ) (Open Access), OBJECTIVE: To investigate immunostimulatory effects of acetylsalicylic acid during experimental human endotoxemia and in sepsis patients. DESIGN: Double-blind, randomized, placebo-controlled study in healthy volunteers and ex vivo stimulation experiments using monocytes of septic patients. SETTING: Intensive care research unit of an university hospital. SUBJECTS: Thirty healthy male volunteers and four sepsis patients. INTERVENTIONS: Healthy volunteers were challenged IV with endotoxin twice, at a 1-week interval, with each challenge consisting of a bolus of 1 ng/kg followed by continuous administration of 1 ng/kg/hr during 3 hours. Volunteers were randomized to acetylsalicylic acid prophylaxis (80 mg acetylsalicylic acid daily for a 14-d period, starting 7 d before the first endotoxin challenge), acetylsalicylic acid treatment (80 mg acetylsalicylic acid daily for the 7-d period in-between both endotoxin challenges), or the control group (receiving placebo). Furthermore, monocytes of sepsis patients were incubated with acetylsalicylic acid preexposed platelets and were subsequently stimulated with endotoxin. MEASUREMENTS AND MAIN RESULTS: Acetylsalicylic acid prophylaxis enhanced plasma tumor necrosis factor-alpha concentrations upon the first endotoxin challenge by 50% compared with the control group (p = 0.02) but did not modulate cytokine responses during the second endotoxin challenge. In contrast, acetylsalicylic acid treatment resulted in enhanced plasma levels of tumor necrosis factor-alpha (+53%; p = 0.02), interleukin-6 (+91%; p = 0.03), and interleukin-8 (+42%; p = 0.02) upon the second challenge, whereas plasma levels of the key antiinflammatory cytokine interleukin-10 were attenuated (-40%; p = 0.003). This proinflammatory phenotype in the acetylsalicylic acid treatment group was accompanied by a decrease in urinary prostaglandin E metabolite levels (-27% +/- 7%; p = 0.01). Ex vivo exposure of platelets to acetylsalicylic acid increased production of tu
- Published
- 2019
10. The influence of hypoxia on platelet function and plasmatic coagulation during systemic inflammation in humans in vivo
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Kiers, D., Tunjungputri, R.N., Borkus, Rowie, Scheffer, G.J., Groot, P.G. de, Urbanus, Rolf T., Ven, A.J.A.M. van der, Pickkers, P., Mast, Q. de, Kox, M., Kiers, D., Tunjungputri, R.N., Borkus, Rowie, Scheffer, G.J., Groot, P.G. de, Urbanus, Rolf T., Ven, A.J.A.M. van der, Pickkers, P., Mast, Q. de, and Kox, M.
- Abstract
Contains fulltext : 207956.pdf (publisher's version ) (Open Access)
- Published
- 2019
11. Comparison of different lots of endotoxin and evaluation of in vivo potency over time in the experimental human endotoxemia model
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Kiers, D., Leijte, G.P., Gerretsen, J., Zwaag, J., Kox, M., Pickkers, P., Kiers, D., Leijte, G.P., Gerretsen, J., Zwaag, J., Kox, M., and Pickkers, P.
- Abstract
Contains fulltext : 201084.pdf (publisher's version ) (Open Access)
- Published
- 2019
12. Short-Term Hypoxia Dampens Inflammation in vivo via Enhanced Adenosine Release and Adenosine 2B Receptor Stimulation
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Kiers, D., Wielockx, Ben, Peters, E., Eijk, L.T., Gerretsen, J., John, A., Janssen, Emmy, Damen, L.A.A., Langereis, J.D., Zomer, A.L., Joosten, L.A., Netea, M.G., Riksen, N.P., Scheffer, G.J., Pickkers, P., Kox, M., Kiers, D., Wielockx, Ben, Peters, E., Eijk, L.T., Gerretsen, J., John, A., Janssen, Emmy, Damen, L.A.A., Langereis, J.D., Zomer, A.L., Joosten, L.A., Netea, M.G., Riksen, N.P., Scheffer, G.J., Pickkers, P., and Kox, M.
- Abstract
Contains fulltext : 194401.pdf (publisher's version ) (Open Access)
- Published
- 2018
13. Markers of Intestinal Damage and their Relation to Cytokine Levels in Cardiac Surgery Patients
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Habes, Q.L.M., Linssen, V., Nooijen, S., Kiers, D., Gerretsen, J., Pickkers, P., Scheffer, G.J., Kox, M., Habes, Q.L.M., Linssen, V., Nooijen, S., Kiers, D., Gerretsen, J., Pickkers, P., Scheffer, G.J., and Kox, M.
- Abstract
Contains fulltext : 175623.pdf (publisher's version ) (Closed access), OBJECTIVES: In patients undergoing cardiac surgery, both extracorporeal circulation (ECC) and intraoperative mesenterial hypoperfusion may account for increased cytokine levels and lead to postoperative gastrointestinal (GI) symptoms. METHODS: We investigated levels of the intestinal damage markers intestinal fatty acid binding protein (I-FABP in plasma [n = 72] and urine [n = 37]), citrulline (in plasma [n = 35]), and claudin-3 (in urine [n = 37]) in patients undergoing aortic or mitral valve surgery with or without coronary artery bypass grafting. Furthermore, the relationship between these markers and the surgery-induced cytokine response was explored by measuring serial plasma levels of tumor necrosis factor-alpha, interleukin (IL)-6, IL-8, and IL-10 (n = 35). Finally, the relationship between markers of intestinal damage and GI-symptoms (abdominal pain, ileus, vomiting, diarrhea, time to first defecation) was assessed. RESULTS: Plasma and urinary I-FABP levels, and urinary claudin-3 levels peaked at the end of surgery, while citrulline levels were not influenced by surgery. ECC duration correlated with plasma I-FABP levels (r = 0.31, P = 0.007). Plasma levels of all measured cytokines increased during surgery, with peak levels observed either at the end of surgery or on the first postoperative day. While ECC duration correlated with IL-6 and IL-8 release (r = 0.43, P = 0.01 and r = 0.36, P = 0.04 respectively), there was no direct relationship between I-FABP and claudin-3 levels and cytokine concentrations. No patients developed significant GI or non-GI complications, and I-FABP and claudin-3 release appeared not to be related to postoperative GI symptoms, although the incidence of these symptoms may have limited a reliable assessment. CONCLUSIONS: Longer duration of ECC is associated with a more pronounced release of intestinal injury markers and inflammatory cytokines, but intestinal injury markers are not directly related to the observed increase in cytokine
- Published
- 2017
14. Enteroendocrine L Cells Sense LPS after Gut Barrier Injury to Enhance GLP-1 Secretion
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Lebrun, L.J., Lenaerts, K., Kiers, D., Barros, J.P. Pais de, Guern, N. Le, Plesnik, J., Thomas, C., Bourgeois, T., Dejong, C.H., Kox, M., Hundscheid, I.H.R., Khan, N.A., Mandard, S., Deckert, V., Pickkers, P., Drucker, D.J., Lagrost, L., Grober, J., Lebrun, L.J., Lenaerts, K., Kiers, D., Barros, J.P. Pais de, Guern, N. Le, Plesnik, J., Thomas, C., Bourgeois, T., Dejong, C.H., Kox, M., Hundscheid, I.H.R., Khan, N.A., Mandard, S., Deckert, V., Pickkers, P., Drucker, D.J., Lagrost, L., and Grober, J.
- Abstract
Contains fulltext : 182548.pdf (publisher's version ) (Open Access), Glucagon-like peptide 1 (GLP-1) is a hormone released from enteroendocrine L cells. Although first described as a glucoregulatory incretin hormone, GLP-1 also suppresses inflammation and promotes mucosal integrity. Here, we demonstrate that plasma GLP-1 levels are rapidly increased by lipopolysaccharide (LPS) administration in mice via a Toll-like receptor 4 (TLR4)-dependent mechanism. Experimental manipulation of gut barrier integrity after dextran sodium sulfate treatment, or via ischemia/reperfusion experiments in mice, triggered a rapid rise in circulating GLP-1. This phenomenon was detected prior to measurable changes in inflammatory status and plasma cytokine and LPS levels. In human subjects, LPS administration also induced GLP-1 secretion. Furthermore, GLP-1 levels were rapidly increased following the induction of ischemia in the human intestine. These findings expand traditional concepts of enteroendocrine L cell biology to encompass the sensing of inflammatory stimuli and compromised mucosal integrity, linking glucagon-like peptide secretion to gut inflammation.
- Published
- 2017
15. Characterization of a model of systemic inflammation in humans in vivo elicited by continuous infusion of endotoxin
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Kiers, D., Koch, R.M., Hamers, L., Gerretsen, J., Thijs, E.J., Ede, L. van, Riksen, N.P., Kox, M., Pickkers, P., Kiers, D., Koch, R.M., Hamers, L., Gerretsen, J., Thijs, E.J., Ede, L. van, Riksen, N.P., Kox, M., and Pickkers, P.
- Abstract
Contains fulltext : 169916.pdf (publisher's version ) (Open Access), Investigating the systemic inflammatory response in patients with critical illness such as sepsis, trauma and burns is complicated due to uncertainties about the onset, duration and severity of the insult. Therefore, in vivo models of inflammation are essential to study the pathophysiology and to evaluate immunomodulatory therapies. Intravenous bolus administration of endotoxin to healthy volunteers is a well-established model of a short-lived systemic inflammatory response, characterized by increased plasma cytokine levels, flu-like symptoms and fever. In contrast, patients suffering from systemic inflammation are often exposed to inflammatory stimuli for an extended period of time. Therefore, continuous infusion of endotoxin may better reflect the kinetics of the inflammatory response encountered in these patients. Herein, we characterize a novel model of systemic inflammation elicited by a bolus infusion of 1 ng/kg, followed by a 3hr continuous infusion of 1 ng/kg/h of endotoxin in healthy volunteers, and compared it with models of bolus administrations of 1 and 2 ng/kg of endotoxin. The novel model was well-tolerated and resulted in a more pronounced increase in plasma cytokine levels with different kinetics and more prolonged symptoms and fever compared with the bolus-only models. Therefore, the continuous endotoxin infusion model provides novel insights into kinetics of the inflammatory response during continuous inflammatory stimuli and accommodates a larger time window to evaluate immunomodulating therapies.
- Published
- 2017
16. A randomised trial on the effect of anti-platelet therapy on the systemic inflammatory response in human endotoxaemia
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Kiers, D., Heijden, W.A. van der, Ede, L. van, Gerretsen, J., Mast, Q. de, Ven, A.J.A.M. van der, Messaoudi, S. El, Rongen, G.A.P.J.M., Gomes, M.E.R., Kox, M., Pickkers, P., Riksen, N.P., Kiers, D., Heijden, W.A. van der, Ede, L. van, Gerretsen, J., Mast, Q. de, Ven, A.J.A.M. van der, Messaoudi, S. El, Rongen, G.A.P.J.M., Gomes, M.E.R., Kox, M., Pickkers, P., and Riksen, N.P.
- Abstract
Contains fulltext : 177777.pdf (publisher's version ) (Closed access), The use of acetylsalicylic acid (ASA) is associated with improved outcome in patients with sepsis, and P2Y12 inhibitors have been suggested to also have immunomodulatory effects. Therefore, we evaluated the effects of clinically relevant combinations of antiplatelet therapy on the immune response in experimental endotoxaemia in humans in vivo. Forty healthy subjects were randomised to seven days of placebo, placebo with ASA, ticagrelor and ASA, or clopidogrel and ASA treatment. Systemic inflammation was elicited at day seven by intravenous administration of Escherichia coli endotoxin. ASA treatment profoundly augmented the plasma concentration of pro-inflammatory cytokines, but did not affect anti-inflammatory cytokines. Addition of either P2Y12 antagonist to ASA did not affect any of the circulating cytokines, except for an attenuation of the ASA-induced increase in TNFalpha by ticagrelor. Systemic inflammation increased plasma adenosine, without differences between groups, and although P2Y12 inhibition impaired platelet reactivity, there was no correlation with cytokine responses.
- Published
- 2017
17. [No glucocorticoids for treatment of sepsis; unless...]
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Kamps, M.J.A., Kiers, D., Pickkers, P., Kamps, M.J.A., Kiers, D., and Pickkers, P.
- Abstract
Item does not contain fulltext, Steroids influence the immune response and blood pressure in patients with septic shock. Many trials have evaluated a putative positive effect of steroids as an adjuvant therapy in patients with sepsis and septic shock, with contradictory outcomes. As a consequence, the use of steroids in sepsis patients varies widely. A recently published randomized clinical trial has demonstrated that treatment with hydrocortisone does not delay or prevent progress to septic shock in patients with sepsis. Based on the current available data, the use of steroids in sepsis should be reserved for those patients who remain severely hemodynamic unstable after fluid resuscitation and vasopressor therapy, or those with a separate indication for steroid therapy. A corticotropin stimulation test to evaluate adrenal insufficiency is not useful.
- Published
- 2017
18. Characterization of a model of systemic inflammation in humans in vivo elicited by continuous infusion of endotoxin
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Kiers, D., primary, Koch, R. M., additional, Hamers, L., additional, Gerretsen, J., additional, Thijs, E. J. M., additional, van Ede, L., additional, Riksen, N. P., additional, Kox, M., additional, and Pickkers, P., additional
- Published
- 2017
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- View/download PDF
19. Reply to: Re: The challenge of Clostridium difficile infection: overview of clinical manifestations, diagnostic tools and therapeutic options
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Postma, N., Kiers, D., Pickkers, P., Postma, N., Kiers, D., and Pickkers, P.
- Abstract
Item does not contain fulltext
- Published
- 2016
20. The challenge of Clostridium difficile infection: Overview of clinical manifestations, diagnostic tools and therapeutic options
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Postma, N., Kiers, D., Pickkers, P., Postma, N., Kiers, D., and Pickkers, P.
- Abstract
Contains fulltext : 152821.pdf (publisher's version ) (Closed access), The most important infectious cause of antibiotic-associated diarrhoea and colitis is Clostridium difficile, which is a Gram-positive, anaerobic, spore-forming, toxin-producing bacillus. In this overview we will discuss the diagnostic and therapeutic management of patients presenting with suspected or proven C. difficile infection (CDI). The clinical spectrum varies from asymptomatic C. difficile carriers to fulminant colitis with multi-organ failure. The onset of symptoms is usually within 2 weeks after initiation of antibiotic treatment. Diagnosis is based on the combination of clinical symptoms and either a positive stool test for C. difficile toxins or endoscopic or histological findings of pseudomembranous colitis. There is no indication for treatment of asymptomatic carriers, but patients with proven CDI should be treated. Treatment consists of cessation of the provoking antibiotic treatment, secondary prevention by infection control strategies, and treatment with metronidazole or vancomycin. Treatment of recurring CDI, severe infection, the need for surgery, and novel alternative potential treatment strategies will be discussed. The concurrent increase in multiresistant colonisation and increasing numbers of asymptomatic carriers of C. difficile will lead to an increase of the situation in which patients with severe infections, treated with broad-spectrum antibiotics, will develop concurrent severe CDI. We will discuss possible therapy strategies for these patients.
- Published
- 2015
21. ALLIANCE COMPETENCE: KEY CAPABILITIES FOR SUCCESS
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Kiers, D., primary
- Published
- 2001
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22. Phosphodiesterase 3 inhibitors do not influence lactate kinetics and clinical outcomes in patients with septic shock: A multicentre cohort study.
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Tai-Passmann S, Slegers CAD, Hemelaar P, Waalders N, Koopmans M, van den Bogaard B, van Lookeren Campagne M, Goedegebuur J, Kuindersma M, Schroten N, van der Elsen F, Grady BPX, van den Beuken WMF, Kiers D, Pickkers P, and van den Oever HLA
- Subjects
- Humans, Male, Female, Retrospective Studies, Aged, Middle Aged, Hospital Mortality, Treatment Outcome, Shock, Septic drug therapy, Shock, Septic mortality, Shock, Septic blood, Lactic Acid blood, Phosphodiesterase 3 Inhibitors therapeutic use, Length of Stay, Intensive Care Units statistics & numerical data
- Abstract
Purpose: We investigated the association between the administration of phosphodiesterase 3 inhibitors (PDE3i) and lactate kinetics, resolution of organ failure, ICU and hospital length of stay (LOS) and hospital mortality in a retrospective cohort of patients with septic shock and persistently elevated lactate concentrations., Material and Methods: Patients with septic shock and two arterial lactate concentrations ≥4 mmol/L with at least 4 h between measurements were eligible. Clinical data of the first four days of admission were collected in an online database. For each patient, the area between the actual lactate concentrations and 2.2 mmol/L (AUC
lact2.2 ), was calculated for three days., Results: Data on 229 patients from 10 hospitals were collected, of whom 123 received PDE3i (54%). First, a linear multivariate model was developed to predict AUClact2.2 (R2 = 0.57). Adding PDE3i as a cofactor did not affect R2 . Second, 60 patients receiving PDE3i at any time between days 0 and 2 were compared to 60 propensity matched no-PDE3i patients. Third, 30 patients who received PDE3i from ICU admission to day 3 were compared to 30 propensity-matched no-PDE3i patients. These analyses showed no differences in AUClact2.2 , SOFA scores, ICU or hospital LOS or hospital mortality between treatment groups., Conclusions: No association was found between the administration of PDE3i and lactate kinetics, resolution of organ failure, ICU or hospital LOS or hospital mortality., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier Inc.)- Published
- 2024
- Full Text
- View/download PDF
23. Neo-epitope detection identifies extracellular matrix turnover in systemic inflammation and sepsis: an exploratory study.
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Fan Y, Moser J, van Meurs M, Kiers D, Sand JMB, Leeming DJ, Pickkers P, Burgess JK, Kox M, and Pillay J
- Subjects
- Humans, Male, Lipopolysaccharides, Extracellular Matrix, Epitopes, Escherichia coli, Shock, Septic, Sepsis
- Abstract
Background: Sepsis is associated with high morbidity and mortality, primarily due to systemic inflammation-induced tissue damage, resulting organ failure, and impaired recovery. Regulated extracellular matrix (ECM) turnover is crucial for maintaining tissue homeostasis in health and in response to disease-related changes in the tissue microenvironment. Conversely, uncontrolled turnover can contribute to tissue damage. Systemic Inflammation is implicated to play a role in the regulation of ECM turnover, but the relationship between the two is largely unclear., Methods: We performed an exploratory study in 10 healthy male volunteers who were intravenously challenged with 2 ng/kg lipopolysaccharide (LPS, derived from Escherichia coli) to induce systemic inflammation. Plasma samples were collected before (T0) and after (T 1 h, 3 h, 6 h and 24 h) the LPS challenge. Furthermore, plasma was collected from 43 patients with septic shock on day 1 of ICU admission. Circulating neo-epitopes of extracellular matrix turnover, including ECM degradation neo-epitopes of collagen type I (C1M), type III (C3M), type IV (C4Ma3), and type VI (C6M), elastin (ELP-3) and fibrin (X-FIB), as well as the ECM synthesis neo-epitopes of collagen type III (PRO-C3), collagen type IV (PRO-C4) and collagen type VI (PRO-C6) were measured by ELISA. Patient outcome data were obtained from electronic patient records., Results: Twenty-four hours after LPS administration, all measured ECM turnover neo-epitopes, except ELP-3, were increased compared to baseline levels. In septic shock patients, concentrations of all measured ECM neo-epitopes were higher compared to healthy controls. In addition, concentrations of C6M, ELP-3 and X-FIB were higher in patients with septic shock who ultimately did not survive (N = 7) compared to those who recovered (N = 36)., Conclusion: ECM turnover is induced in a model of systemic inflammation in healthy volunteers and was observed in patients with septic shock. Understanding interactions between systemic inflammation and ECM turnover may provide further insight into mechanisms underlying acute and persistent organ failure in sepsis., (© 2024. The Author(s).)
- Published
- 2024
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24. Systemic inflammation down-regulates glyoxalase-1 expression: an experimental study in healthy males.
- Author
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Driessen RGH, Kiers D, Schalkwijk CG, Scheijen JLJM, Gerretsen J, Pickkers P, van de Poll MCG, van der Horst ICC, Bergmans DCJJ, Kox M, and van Bussel BCT
- Subjects
- Adolescent, Adult, Biomarkers blood, Down-Regulation, Endotoxemia blood, Endotoxemia genetics, Healthy Volunteers, Humans, Hypoxia blood, Hypoxia genetics, Inflammation blood, Inflammation genetics, Lactic Acid blood, Lactoylglutathione Lyase genetics, Male, Young Adult, Endotoxemia enzymology, Hypoxia enzymology, Inflammation enzymology, Lactoylglutathione Lyase blood, Pyruvaldehyde blood
- Abstract
Background: Hypoxia and inflammation are hallmarks of critical illness, related to multiple organ failure. A possible mechanism leading to multiple organ failure is hypoxia- or inflammation-induced down-regulation of the detoxifying glyoxalase system that clears dicarbonyl stress. The dicarbonyl methylglyoxal (MGO) is a highly reactive agent produced by metabolic pathways such as anaerobic glycolysis and gluconeogenesis. MGO leads to protein damage and ultimately multi-organ failure. Whether detoxification of MGO into D-lactate by glyoxalase functions appropriately under conditions of hypoxia and inflammation is largely unknown. We investigated the effect of inflammation and hypoxia on the MGO pathway in humans in vivo., Methods: After prehydration with glucose 2.5% solution, ten healthy males were exposed to hypoxia (arterial saturation 80-85%) for 3.5 h using an air-tight respiratory helmet, ten males to experimental endotoxemia (LPS 2 ng/kg i.v.), ten males to LPS+hypoxia and ten males to none of these interventions (control group). Serial blood samples were drawn, and glyoxalase-1 mRNA expression, MGO, methylglyoxal-derived hydroimidazolone-1 (MG-H1), D-lactate and L-lactate levels, were measured serially., Results: Glyoxalase-1 mRNA expression decreased in the LPS (β (95%CI); -0.87 (-1.24; -0.50) and the LPS+hypoxia groups; -0.78 (-1.07; -0.48) (P<0.001). MGO was equal between groups, whereas MG-H1 increased over time in the control group only (P=0.003). D-Lactate was increased in all four groups. L-Lactate was increased in all groups, except in the control group., Conclusion: Systemic inflammation downregulates glyoxalase-1 mRNA expression in humans. This is a possible mechanism leading to cell damage and multi-organ failure in critical illness with potential for intervention., (© 2021 The Author(s).)
- Published
- 2021
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25. Hypoxia attenuates inflammation-induced hepcidin synthesis during experimental human endotoxemia.
- Author
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Kiers D, van Eijk LT, van der Hoeven JG, Swinkels DW, Pickkers P, and Kox M
- Subjects
- Biomarkers, Disease Susceptibility, Endotoxemia diagnosis, Endotoxemia therapy, Hepcidins blood, Homeostasis, Humans, Inflammation metabolism, Iron blood, Iron metabolism, Protein Binding, Endotoxemia etiology, Endotoxemia metabolism, Hepcidins biosynthesis, Hypoxia metabolism
- Published
- 2019
- Full Text
- View/download PDF
26. Treatment With Acetylsalicylic Acid Reverses Endotoxin Tolerance in Humans In Vivo: A Randomized Placebo-Controlled Study.
- Author
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Leijte GP, Kiers D, van der Heijden W, Jansen A, Gerretsen J, Boerrigter V, Netea MG, Kox M, and Pickkers P
- Subjects
- Adult, Aged, Dose-Response Relationship, Drug, Double-Blind Method, Female, Humans, Male, Middle Aged, Sepsis prevention & control, Aspirin therapeutic use, Endotoxemia drug therapy, Endotoxins immunology, Sepsis immunology
- Abstract
Objective: To investigate immunostimulatory effects of acetylsalicylic acid during experimental human endotoxemia and in sepsis patients., Design: Double-blind, randomized, placebo-controlled study in healthy volunteers and ex vivo stimulation experiments using monocytes of septic patients., Setting: Intensive care research unit of an university hospital., Subjects: Thirty healthy male volunteers and four sepsis patients., Interventions: Healthy volunteers were challenged IV with endotoxin twice, at a 1-week interval, with each challenge consisting of a bolus of 1 ng/kg followed by continuous administration of 1 ng/kg/hr during 3 hours. Volunteers were randomized to acetylsalicylic acid prophylaxis (80 mg acetylsalicylic acid daily for a 14-d period, starting 7 d before the first endotoxin challenge), acetylsalicylic acid treatment (80 mg acetylsalicylic acid daily for the 7-d period in-between both endotoxin challenges), or the control group (receiving placebo). Furthermore, monocytes of sepsis patients were incubated with acetylsalicylic acid preexposed platelets and were subsequently stimulated with endotoxin., Measurements and Main Results: Acetylsalicylic acid prophylaxis enhanced plasma tumor necrosis factor-α concentrations upon the first endotoxin challenge by 50% compared with the control group (p = 0.02) but did not modulate cytokine responses during the second endotoxin challenge. In contrast, acetylsalicylic acid treatment resulted in enhanced plasma levels of tumor necrosis factor-α (+53%; p = 0.02), interleukin-6 (+91%; p = 0.03), and interleukin-8 (+42%; p = 0.02) upon the second challenge, whereas plasma levels of the key antiinflammatory cytokine interleukin-10 were attenuated (-40%; p = 0.003). This proinflammatory phenotype in the acetylsalicylic acid treatment group was accompanied by a decrease in urinary prostaglandin E metabolite levels (-27% ± 7%; p = 0.01). Ex vivo exposure of platelets to acetylsalicylic acid increased production of tumor necrosis factor-α (+66%) and decreased production of interleukin-10 (-23%) by monocytes of sepsis patients., Conclusions: Treatment, but not prophylaxis, with low-dose acetylsalicylic acid, partially reverses endotoxin tolerance in humans in vivo by shifting response toward a proinflammatory phenotype. This acetylsalicylic acid-induced proinflammatory shift was also observed in septic monocytes, signifying that patients suffering from sepsis-induced immunoparalysis might benefit from initiating acetylsalicylic acid treatment.
- Published
- 2019
- Full Text
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27. Comparison of different lots of endotoxin and evaluation of in vivo potency over time in the experimental human endotoxemia model.
- Author
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Kiers D, Leijte GP, Gerretsen J, Zwaag J, Kox M, and Pickkers P
- Subjects
- Adolescent, Adult, Endotoxemia chemically induced, Heart Rate, Humans, Hydrocortisone metabolism, Infusions, Intravenous, Leukocyte Count, Male, Time Factors, Young Adult, Cytokines therapeutic use, Endotoxemia immunology, Endotoxins immunology, Lot Quality Assurance Sampling methods
- Abstract
The experimental human endotoxemia model is used to study the systemic inflammatory response in vivo. The previously used lot of endotoxin, which was used for over a decade, is no longer approved for human use and a new Good Manufacturing Practices-grade batch has become available. We compared the inflammatory response induced by either bolus or continuous administration of either the previously used lot #1188844 or new lots of endotoxin (#94332B1 and #94332B4). Compared with lot #1188844, bolus administration of lot #94332B1 induced a more pronounced systemic inflammatory response including higher plasma levels of pro-inflammatory cytokines and more pronounced clinical signs of inflammation. In contrast, continuous infusion of lot #94332B4 resulted in a slightly less pronounced inflammatory response compared with lot #1188844. Furthermore, we evaluated whether lot #1188844 displayed in vivo potency loss by reviewing inflammatory parameters obtained from 17 endotoxemia studies performed in our centre between 2007 and 2016. Despite inter-study variability in endotoxemia-induced effects on temperature, heart rate, symptoms, and leukocyte counts, the magnitude of these effects did not decrease over time. In conclusion, although all lots of endotoxin induce a pronounced inflammatory response, the magnitude differs between lots. We observed no potency loss of endotoxin over time.
- Published
- 2019
- Full Text
- View/download PDF
28. The influence of hypoxia on platelet function and plasmatic coagulation during systemic inflammation in humans in vivo .
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Kiers D, Tunjungputri RN, Borkus R, Scheffer GJ, de Groot PG, Urbanus RT, van der Ven AJ, Pickkers P, de Mast Q, and Kox M
- Subjects
- Healthy Volunteers, Humans, Male, Blood Platelets metabolism, Cell Hypoxia genetics, Inflammation blood, Platelet Function Tests methods
- Abstract
Systemic inflammation and hypoxia frequently occur simultaneously in critically ill patients, and are both associated with platelet activation and coagulopathy. However, human in vivo data on the effects of hypoxia on platelet function and plasmatic coagulation under systemic inflammatory conditions are lacking. In the present study, 20 healthy male volunteers were randomized to either 3.5 h of hypoxia (peripheral saturation 80-85%) or normoxia (room air), and systemic inflammation was elicited by intravenous administration of 2 ng/kg endotoxin. Various parameters of platelet function and plasmatic coagulation were determined serially. Endotoxemia resulted in increased circulating platelet-monocyte complexes and enhanced platelet reactivity, effects which were attenuated by hypoxia. Furthermore, endotoxin administration resulted in decreased plasma levels of platelet factor-4 levels and increased concentrations of von Willebrand factor. These endotoxemia-induced effects were not influenced by hypoxia. Neither endotoxemia nor hypoxia affected thrombin generation. In conclusion, our data reveal that hypoxia attenuates the endotoxemia-induced increases in platelet-monocyte formation and platelet reactivity, while leaving parameters of plasmatic coagulation unaffected.
- Published
- 2019
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- View/download PDF
29. Short-Term Hypoxia Dampens Inflammation in vivo via Enhanced Adenosine Release and Adenosine 2B Receptor Stimulation.
- Author
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Kiers D, Wielockx B, Peters E, van Eijk LT, Gerretsen J, John A, Janssen E, Groeneveld R, Peters M, Damen L, Meneses AM, Krüger A, Langereis JD, Zomer AL, Blackburn MR, Joosten LA, Netea MG, Riksen NP, van der Hoeven JG, Scheffer GJ, Eltzschig HK, Pickkers P, and Kox M
- Subjects
- Adenosine blood, Animals, Disease Models, Animal, Endotoxemia blood, Endotoxemia genetics, Humans, Hypoxia blood, Hypoxia genetics, Hypoxia-Inducible Factor 1, alpha Subunit genetics, Interleukin-10 genetics, Interleukin-10 metabolism, Mice, Receptors, Purinergic P1 metabolism, Up-Regulation, Adenosine metabolism, Endotoxemia immunology, Hypoxia immunology, Interleukin-10 blood
- Abstract
Hypoxia and inflammation are closely intertwined phenomena. Critically ill patients often suffer from systemic inflammatory conditions and concurrently experience short-lived hypoxia. We evaluated the effects of short-term hypoxia on systemic inflammation, and show that it potently attenuates pro-inflammatory cytokine responses during murine endotoxemia. These effects are independent of hypoxia-inducible factors (HIFs), but involve augmented adenosine levels, in turn resulting in an adenosine 2B receptor-mediated post-transcriptional increase of interleukin (IL)-10 production. We translated our findings to humans using the experimental endotoxemia model, where short-term hypoxia resulted in enhanced plasma concentrations of adenosine, augmentation of endotoxin-induced circulating IL-10 levels, and concurrent attenuation of the pro-inflammatory cytokine response. Again, HIFs were shown not to be involved. Taken together, we demonstrate that short-term hypoxia dampens the systemic pro-inflammatory cytokine response through enhanced purinergic signaling in mice and men. These effects may contribute to outcome and provide leads for immunomodulatory treatment strategies for critically ill patients., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2018
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30. [Weak respiratory muscles as a first sign of ALS: symptoms may put the physician on the wrong track].
- Author
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Kiers D, Meermans M, Verstraete E, and van Leeuwen HJ
- Subjects
- Aged, 80 and over, Diagnosis, Differential, Exercise Tolerance, Fatal Outcome, Humans, Male, Muscle Weakness etiology, Muscle Weakness physiopathology, Neurologic Examination methods, Respiratory Muscles physiopathology, Amyotrophic Lateral Sclerosis complications, Amyotrophic Lateral Sclerosis diagnosis, Amyotrophic Lateral Sclerosis physiopathology, Delayed Diagnosis prevention & control, Respiratory Insufficiency diagnosis, Respiratory Insufficiency etiology, Respiratory Insufficiency physiopathology
- Abstract
Background: Patients with decreased exercise tolerance and orthopnoea are often referred to an internist, a cardiologist or a pulmonologist. These symptoms can also be caused by weakness of the respiratory muscles, as an indication of a neuromuscular disease. If these symptoms are not recognized as such, this may result in a delay in timely diagnosis., Case Description: An 82-year-old man had suffered from decreased exercise tolerance for 18 months. For the last months he had been sleeping upright and had lost 20 kg in weight. Analyses by the cardiologist and the internist had not led to a definitive diagnosis. He was finally brought to the emergency department with loss of consciousness and hypercapnic respiratory insufficiency. Neurological examination was suggestive of motor neuron disease such as progressive spinal muscular atrophy or amyotrophic lateral sclerosis. The patient died within 24 hours of admission., Conclusion: Patients with symptoms resulting from respiratory muscle weakness are commonly referred to non-neurological specialists, leading to a delay in diagnosis and treatment of an underlying neuromuscular disease.
- Published
- 2018
31. Enteroendocrine L Cells Sense LPS after Gut Barrier Injury to Enhance GLP-1 Secretion.
- Author
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Lebrun LJ, Lenaerts K, Kiers D, Pais de Barros JP, Le Guern N, Plesnik J, Thomas C, Bourgeois T, Dejong CHC, Kox M, Hundscheid IHR, Khan NA, Mandard S, Deckert V, Pickkers P, Drucker DJ, Lagrost L, and Grober J
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Animals, Calcium Signaling drug effects, Cells, Cultured, Colitis chemically induced, Colitis metabolism, Colitis pathology, Cytokines blood, Cytokines genetics, Cytokines metabolism, Dextran Sulfate pharmacology, Enteroendocrine Cells cytology, Enteroendocrine Cells drug effects, Enteroendocrine Cells metabolism, Humans, Ileum metabolism, Interleukin-6 deficiency, Interleukin-6 genetics, Male, Mice, Mice, Inbred C57BL, Middle Aged, Myristic Acids blood, Proglucagon metabolism, Proprotein Convertase 1 metabolism, Reperfusion Injury metabolism, Reperfusion Injury pathology, Toll-Like Receptor 4 deficiency, Toll-Like Receptor 4 genetics, Toll-Like Receptor 4 metabolism, Young Adult, Glucagon-Like Peptide 1 metabolism, Ileum drug effects, Lipopolysaccharides toxicity
- Abstract
Glucagon-like peptide 1 (GLP-1) is a hormone released from enteroendocrine L cells. Although first described as a glucoregulatory incretin hormone, GLP-1 also suppresses inflammation and promotes mucosal integrity. Here, we demonstrate that plasma GLP-1 levels are rapidly increased by lipopolysaccharide (LPS) administration in mice via a Toll-like receptor 4 (TLR4)-dependent mechanism. Experimental manipulation of gut barrier integrity after dextran sodium sulfate treatment, or via ischemia/reperfusion experiments in mice, triggered a rapid rise in circulating GLP-1. This phenomenon was detected prior to measurable changes in inflammatory status and plasma cytokine and LPS levels. In human subjects, LPS administration also induced GLP-1 secretion. Furthermore, GLP-1 levels were rapidly increased following the induction of ischemia in the human intestine. These findings expand traditional concepts of enteroendocrine L cell biology to encompass the sensing of inflammatory stimuli and compromised mucosal integrity, linking glucagon-like peptide secretion to gut inflammation., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
- Full Text
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32. A randomised trial on the effect of anti-platelet therapy on the systemic inflammatory response in human endotoxaemia.
- Author
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Kiers D, van der Heijden WA, van Ede L, Gerretsen J, de Mast Q, van der Ven AJ, El Messaoudi S, Rongen GA, Gomes M, Kox M, Pickkers P, and Riksen NP
- Subjects
- Adenosine adverse effects, Adenosine therapeutic use, Administration, Intravenous, Adolescent, Adult, Aspirin adverse effects, Cells, Cultured, Clopidogrel, Cytokines blood, Drug Therapy, Combination, Endotoxemia blood, Endotoxemia diagnosis, Endotoxins administration & dosage, Healthy Volunteers, Humans, Inflammation blood, Inflammation diagnosis, Inflammation Mediators blood, Male, Netherlands, Platelet Aggregation Inhibitors adverse effects, Prospective Studies, Purinergic P2Y Receptor Antagonists adverse effects, Ticagrelor, Ticlopidine adverse effects, Ticlopidine therapeutic use, Time Factors, Treatment Outcome, Young Adult, Adenosine analogs & derivatives, Aspirin therapeutic use, Endotoxemia drug therapy, Inflammation drug therapy, Platelet Activation drug effects, Platelet Aggregation Inhibitors therapeutic use, Purinergic P2Y Receptor Antagonists therapeutic use, Ticlopidine analogs & derivatives
- Abstract
The use of acetylsalicylic acid (ASA) is associated with improved outcome in patients with sepsis, and P2Y
12 inhibitors have been suggested to also have immunomodulatory effects. Therefore, we evaluated the effects of clinically relevant combinations of antiplatelet therapy on the immune response in experimental endotoxaemia in humans in vivo. Forty healthy subjects were randomised to seven days of placebo, placebo with ASA, ticagrelor and ASA, or clopidogrel and ASA treatment. Systemic inflammation was elicited at day seven by intravenous administration of Escherichia coli endotoxin. ASA treatment profoundly augmented the plasma concentration of pro-inflammatory cytokines, but did not affect anti-inflammatory cytokines. Addition of either P2Y12 antagonist to ASA did not affect any of the circulating cytokines, except for an attenuation of the ASA-induced increase in TNFα by ticagrelor. Systemic inflammation increased plasma adenosine, without differences between groups, and although P2Y12 inhibition impaired platelet reactivity, there was no correlation with cytokine responses.- Published
- 2017
- Full Text
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33. Markers of Intestinal Damage and their Relation to Cytokine Levels in Cardiac Surgery Patients.
- Author
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Habes QLM, Linssen V, Nooijen S, Kiers D, Gerretsen J, Pickkers P, Scheffer GJ, and Kox M
- Subjects
- Aged, Citrulline blood, Citrulline metabolism, Citrulline urine, Claudin-3 blood, Claudin-3 metabolism, Claudin-3 urine, Cytokines metabolism, Fatty Acid-Binding Proteins blood, Fatty Acid-Binding Proteins metabolism, Fatty Acid-Binding Proteins urine, Female, Humans, Interleukin-10 blood, Interleukin-10 metabolism, Interleukin-10 urine, Interleukin-6 blood, Interleukin-6 metabolism, Interleukin-6 urine, Interleukin-8 blood, Interleukin-8 metabolism, Interleukin-8 urine, Intestinal Diseases metabolism, Intestinal Mucosa metabolism, Male, Thoracic Surgery, Cytokines blood, Cytokines urine, Intestinal Diseases blood, Intestinal Diseases urine, Intestines injuries
- Abstract
Objectives: In patients undergoing cardiac surgery, both extracorporeal circulation (ECC) and intraoperative mesenterial hypoperfusion may account for increased cytokine levels and lead to postoperative gastrointestinal (GI) symptoms., Methods: We investigated levels of the intestinal damage markers intestinal fatty acid binding protein (I-FABP in plasma [n = 72] and urine [n = 37]), citrulline (in plasma [n = 35]), and claudin-3 (in urine [n = 37]) in patients undergoing aortic or mitral valve surgery with or without coronary artery bypass grafting. Furthermore, the relationship between these markers and the surgery-induced cytokine response was explored by measuring serial plasma levels of tumor necrosis factor-α, interleukin (IL)-6, IL-8, and IL-10 (n = 35). Finally, the relationship between markers of intestinal damage and GI-symptoms (abdominal pain, ileus, vomiting, diarrhea, time to first defecation) was assessed., Results: Plasma and urinary I-FABP levels, and urinary claudin-3 levels peaked at the end of surgery, while citrulline levels were not influenced by surgery. ECC duration correlated with plasma I-FABP levels (r = 0.31, P = 0.007). Plasma levels of all measured cytokines increased during surgery, with peak levels observed either at the end of surgery or on the first postoperative day. While ECC duration correlated with IL-6 and IL-8 release (r = 0.43, P = 0.01 and r = 0.36, P = 0.04 respectively), there was no direct relationship between I-FABP and claudin-3 levels and cytokine concentrations. No patients developed significant GI or non-GI complications, and I-FABP and claudin-3 release appeared not to be related to postoperative GI symptoms, although the incidence of these symptoms may have limited a reliable assessment., Conclusions: Longer duration of ECC is associated with a more pronounced release of intestinal injury markers and inflammatory cytokines, but intestinal injury markers are not directly related to the observed increase in cytokine levels or GI-symptoms. These findings indicate that ECC duration contributes to the cytokine response observed in cardiac surgery patients and that intestinal injury itself is not a causative factor for this response.
- Published
- 2017
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34. [No glucocorticoids for treatment of sepsis; unless…].
- Author
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Kamps MJA, Kiers D, and Pickkers P
- Subjects
- Adrenal Insufficiency, Humans, Hydrocortisone, Shock, Septic, Glucocorticoids adverse effects, Glucocorticoids therapeutic use, Sepsis drug therapy
- Abstract
Steroids influence the immune response and blood pressure in patients with septic shock. Many trials have evaluated a putative positive effect of steroids as an adjuvant therapy in patients with sepsis and septic shock, with contradictory outcomes. As a consequence, the use of steroids in sepsis patients varies widely. A recently published randomized clinical trial has demonstrated that treatment with hydrocortisone does not delay or prevent progress to septic shock in patients with sepsis. Based on the current available data, the use of steroids in sepsis should be reserved for those patients who remain severely hemodynamic unstable after fluid resuscitation and vasopressor therapy, or those with a separate indication for steroid therapy. A corticotropin stimulation test to evaluate adrenal insufficiency is not useful.
- Published
- 2017
35. Reply to: Re: The challenge of Clostridium difficile infection: overview of clinical manifestations, diagnostic tools and therapeutic options.
- Author
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Postma N, Kiers D, and Pickkers P
- Subjects
- Enterocolitis, Pseudomembranous drug therapy, Humans, Clostridioides difficile, Clostridium Infections drug therapy
- Published
- 2016
- Full Text
- View/download PDF
36. The challenge of Clostridium difficile infection: Overview of clinical manifestations, diagnostic tools and therapeutic options.
- Author
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Postma N, Kiers D, and Pickkers P
- Subjects
- Case Management, Clostridium Infections diagnosis, Clostridium Infections therapy, Colitis diagnosis, Colitis therapy, Humans, Biological Therapy methods, Clostridioides difficile isolation & purification, Clostridium Infections pathology, Colitis pathology, Diagnostic Tests, Routine methods, Drug Therapy methods, Surgical Procedures, Operative methods
- Abstract
The most important infectious cause of antibiotic-associated diarrhoea and colitis is Clostridium difficile, which is a Gram-positive, anaerobic, spore-forming, toxin-producing bacillus. In this overview we will discuss the diagnostic and therapeutic management of patients presenting with suspected or proven C. difficile infection (CDI). The clinical spectrum varies from asymptomatic C. difficile carriers to fulminant colitis with multi-organ failure. The onset of symptoms is usually within 2 weeks after initiation of antibiotic treatment. Diagnosis is based on the combination of clinical symptoms and either a positive stool test for C. difficile toxins or endoscopic or histological findings of pseudomembranous colitis. There is no indication for treatment of asymptomatic carriers, but patients with proven CDI should be treated. Treatment consists of cessation of the provoking antibiotic treatment, secondary prevention by infection control strategies, and treatment with metronidazole or vancomycin. Treatment of recurring CDI, severe infection, the need for surgery, and novel alternative potential treatment strategies will be discussed. The concurrent increase in multiresistant colonisation and increasing numbers of asymptomatic carriers of C. difficile will lead to an increase of the situation in which patients with severe infections, treated with broad-spectrum antibiotics, will develop concurrent severe CDI. We will discuss possible therapy strategies for these patients., (Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
37. Short-term hyperoxia does not exert immunologic effects during experimental murine and human endotoxemia.
- Author
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Kiers D, Gerretsen J, Janssen E, John A, Groeneveld R, van der Hoeven JG, Scheffer GJ, Pickkers P, and Kox M
- Subjects
- Animals, Blood Gas Analysis, Body Temperature, Cytokines metabolism, Disease Models, Animal, Endotoxemia physiopathology, Hemodynamics, Humans, Inflammation Mediators, Leukocyte Count, Mice, Neutrophils immunology, Neutrophils metabolism, Oxygen Consumption, Phagocytosis immunology, Reactive Oxygen Species metabolism, Time Factors, Endotoxemia immunology, Endotoxemia metabolism, Hyperoxia immunology, Hyperoxia metabolism
- Abstract
Oxygen therapy to maintain tissue oxygenation is one of the cornerstones of critical care. Therefore, hyperoxia is often encountered in critically ill patients. Epidemiologic studies have demonstrated that hyperoxia may affect outcome, although mechanisms are unclear. Immunologic effects might be involved, as hyperoxia was shown to attenuate inflammation and organ damage in preclinical models. However, it remains unclear whether these observations can be ascribed to direct immunosuppressive effects of hyperoxia or to preserved tissue oxygenation. In contrast to these putative anti-inflammatory effects, hyperoxia may elicit an inflammatory response and organ damage in itself, known as oxygen toxicity. Here, we demonstrate that, in the absence of systemic inflammation, short-term hyperoxia (100% O2 for 2.5 hours in mice and 3.5 hours in humans) does not result in increased levels of inflammatory cytokines in both mice and healthy volunteers. Furthermore, we show that, compared with room air, hyperoxia does not affect the systemic inflammatory response elicited by administration of bacterial endotoxin in mice and man. Finally, neutrophil phagocytosis and ROS generation are unaffected by short-term hyperoxia. Our results indicate that hyperoxia does not exert direct anti-inflammatory effects and temper expectations of using it as an immunomodulatory treatment strategy.
- Published
- 2015
- Full Text
- View/download PDF
38. Hypothermia, its principles and biochemical disturbances.
- Author
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BOERE LA, DERLAGEN N, and KIERS D
- Subjects
- Humans, Hypothermia
- Published
- 1957
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