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4. ESICM LIVES 2016: part two: Milan, Italy. 1–5 October 2016

Author

Sivakumar, S., Taccone, F. S., Desai, K. A., Lazaridis, C., Skarzynski, M., Sekhon, M., Henderson, W., Griesdale, D., Chapple, L., Deane, A., Williams, L., Strickland, R., Lange, K., Heyland, D., Chapman, M., Rowland, M. J., Garry, P., Westbrook, J., Corkill, R., Antoniades, C. A., Pattinson, K. T., Fatania, G., Strong, A. J., Myers, R. B., Lazaridis, C., Jermaine, C. M., Robertson, C. S., Rusin, C. G., Hofmeijer, J., Sondag, L., Tjepkema-Cloostermans, M. C., Beishuizen, A., Bosch, F. H., van Putten, M. J. A. M., Carteron, L., Patet, C., Solari, D., Oddo, M., Ali, M. A., Dias, C., Almeida, R., Vaz-Ferreira, A., Silva, J., Monteiro, E., Cerejo, A., Rocha, A. P., Elsayed, A. A., Abougabal, A. M., Beshey, B. N., Alzahaby, K. M., Pozzebon, S., Ortiz, A. Blandino, Cristallini, S., Lheureux, O., Brasseur, A., Vincent, J. L., Creteur, J., Taccone, F. S., Hravnak, M., Yousef, K., Chang, Y., Crago, E., Friedlander, R. M., Abdelmonem, S. A., Tahon, S. A., Helmy, T. A., Meligy, H. S., Puig, F., Dunn-Siegrist, I., Pugin, J., Gupta, S., Govil, D., Srinivasan, S., Patel, S. J., N, J. K., Gupta, A., Tomar, D. S., Shafi, M., Harne, R., Arora, D. P., Talwar, N., Mazumdar, S., Papakrivou, E. E., Makris, D., Manoulakas, E., Tsolaki, B., Karadodas, B., Zakynthinos, E., Garcia, I. Palacios, Martin, A. Diaz, Encinares, V. Sanchez, Ibañez, M. Pachón, Montero, J. Garnacho, Labrador, G., Cangueiro, T. Cebrero, Poulose, V., Koh, J., Kam, J. W., Yeter, H., Kara, A., Aktepe, O., Topeli, A., Tsolakoglou, I., Intas, G., Stergiannis, P., Kolaros, A. A., Chalari, E., Athanasiadou, E., Martika, A., Fildisis, G., Faivre, V., Mengelle, C., Favier, B., Payen, D., Poppe, A., Winkler, M. S., Mudersbach, E., Schreiber, J., Wruck, M. L., Schwedhelm, E., Kluge, S., Zöllner, C., Tavladaki, T., Spanaki, A. M., Dimitriou, H., Kondili, E., Choulaki, C., Meleti, E., Kafetzopoulos, D., Georgopoulos, D., Briassoulis, G., la Torre, A. García-de, de la Torre-Prados, M. V., Tsvetanova-Spasova, T., Nuevo-Ortega, P., Rueda-Molina, C., Fernández-Porcel, A., Camara-Sola, E., Salido-Díaz, L., García-Alcántara, A., Tavladaki, T., Spanaki, A. M., Dimitriou, H., Kondili, E., Choulaki, C., Meleti, D. E., Kafetzopoulos, D., Georgopoulos, D., Briassoulis, G., Suberviola, B., Riera, J., Rellan, L., Sanchez, M., Robles, J. C., Lopez, E., Vicente, R., Miñambres, E., Santibañez, M., Le Guen, M., Moore, J., Mason, N., Windpassinger, M., Plattner, O., Mascha, E., Sessler, D. I., Research, Outcomes, Melia, U., Fontanet, J., van den Berg, J. P., Struys, M. M. R. F., Vereecke, H. E. M., Jensen, E. W., Rood, P. J. T., van de Schoor, F., van Tertholen, K., Pickkers, P., van den Boogaard, M., Beardow, Z. J., Redhead, H., Paramasivam, K., Numan, T., van den Boogaard, M., Kamper, A. M., Rood, P., Peelen, L. M., Zeman, P. M., Slooter, A. J., van Ewijk, C. E., Jacobs, G. E., Girbes, A. R. J., Myatra, S. N., Harish, M. M., Prabu, N. R., Siddiqui, S., Kulkarni, A. P., Divatia, J. V., Murbach, L. D., Leite, M. A., Osaku, E. F., Costa, C. R. L. M., Pelenz, M., Neitzke, N. M., Moraes, M. M., Jaskowiak, J. L., Silva, M. M. M., Zaponi, R. S., Abentroth, L. R. L., Ogasawara, S. M., Jorge, A. C., Duarte, P. A. D., Hernández-Sánchez, N., Sánchez-Hurtado, L. A., García-Guillen, F. J., Ñamendys-Silva, S. A., Maghsoudi, B., Emami, M., Khosravi, M. B., Zand, F., Tabatabaie, H. R., Masjedi, M., Sabetiyan, G., Mokri, A., Troubleyn, J., Diltoer, M., Jacobs, R., Nguyen, D. N., De Waele, E., De Regt, J., Honoré, P. M., Van Gorp, V., Spapen, H. D., Contreras, R. S., Toapanta, N. D., Moreno, G., Sabater, J., Torrado, H., Gonzalez, M., Marin, M., Farigola, E., Gonzalez, A., Fernandez, J., Vera, A., Gisbert, X., Juliá, C., Uya, J., Corral, L., Elias-Jones, I., Gemmell, L., MacKay, A., Randall, D., Adwaney, A., Blunden, M., Prowle, J. R., Kirwan, C. J., Thomas, N., Martin, A., Owen, H., Darwin, L., Conway, D., Atkinson, D., Sharman, M., Moore, J., Barbanti, C., Amour, J., Gaudard, P., Rozec, B., Mauriat, P., M’rini, M., Leger, P. L., Cambonie, G., Liet, J. M., Girard, C., Laroche, S., Damas, P., Assaf, Z., Loron, G., Lecourt, L., Pouard, P., Randall, D., Adwaney, A., Blunden, M., Prowle, J.R., Kirwan, C. J., Kim, S. H., Na, S., Kim, J., Oh, S. Y., Jung, C. W., Yoo, S. H., Min, S. H., Chung, E. J., Lee, H., Lee, N. J., Lee, K. W., Suh, K. S., Ryu, H. G., Marshall, D. C., Goodson, R. J., Salciccioli, J. D., Shalhoub, J., Potter, E. K., Kirk-Bayley, J., Karanjia, N. D., Forni, L. G., Creagh-Brown, B. C., Bossy, M., Nyman, M., Tailor, A., Creagh-Brown, B., D’Antini, D., Spadaro, S., Valentino, F., Sollitto, F., Cinnella, G., Mirabella, L., Calvo, F. J. Redondo, Bejarano, N., Padilla, D., Baladron, V., Villajero, P., Villazala, R., Redondo, J., Yuste, A. S., Liu, J., Shen, F., Teboul, J. L., Anguel, N., Beurton, A., Bezaz, N., Richard, C., Monnet, X., Fossali, T., Colombo, R., Ottolina, D., Rossetti, M., Mazzucco, C., Marchi, A., Porta, A., Catena, E., Tollisen, K. H., Andersen, G. Ø., Heyerdahl, F., Jacobsen, D., de Waard, M. C., Girbes, A. R. J., van IJzendoorn, M. C. O., Buter, H., Kingma, W. P., Navis, G. J., Boerma, E. C., Rulisek, J., Balik, M., Zacharov, S., Kim, H. S., Jeon, S. J., Namgung, H., Lee, E., Lee, E., Cho, Y. J., Lee, Y. J., Huang, A., Cioccari, L., Luethi, N., Mårtensson, J., Bellomo, R., Forsberg, M., Edman, G., Höjer, J., Forsberg, S., Freile, M. T. Chiquito, Hidalgo, F. N., Molina, J. A. Martinez, Lecumberri, R., Rosselló, A. Figuerola, Travieso, P. Medrano, Leon, G. Tuero, Sanchez, J. Gonzalez, Frias, L. Sahuquillo, Rosello, D. Balsells, Verdejo, J. A. Garcia, Serrano, J. A. Noria, Winterwerp, D., van Galen, T., Vazin, A., Karimzade, I., Zand, A., Ozen, E., Ekemen, S., Akcan, A., Sen, E., Yelken, B. Buyukkidan, Kureshi, N., Fenerty, L., Thibault-Halman, G., Erdogan, M., Walling, S., Green, R. S., Clarke, D. B., Briassoulis, P., Kalimeris, K., Ntzouvani, A., Nomikos, T., Papaparaskeva, K., Politi, E., Kostopanagiotou, G., Crewdson, K., Rehn, M., Weaver, A., Brohi, K., Lockey, D., Wright, S., Thomas, K., Baker, C., Mansfield, L., Stafford, V., Wade, C., Watson, G., Bryant, A., Chadwick, T., Shen, J., Wilkinson, J., Furneval, J., Henderson, A., Hugill, K., Howard, P., Roy, A., Bonner, S., Baudouin, S., Ramírez, C. Sánchez, Escalada, S. Hípola, Viera, M. A. Hernández, Santana, M. Cabrera, Balcázar, L. Caipe, Monroy, N. Sangil, Campelo, F. Artiles, Vázquez, C. F. Lübbe, Santana, P. Saavedra, Santana, S. Ruiz, Carteron, L., Patet, C., Quintard, H., Solari, D., Bouzat, P., Oddo, M., Wollersheim, T., Malleike, J., Haas, K., Carbon, N., Schneider, J., Birchmeier, C., Fielitz, J., Spuler, S., Weber-Carstens, S., Enseñat, L., Pérez-Madrigal, A., Saludes, P., Proença, L., Gruartmoner, G., Espinal, C., Mesquida, J., Huber, W., Eckmann, M., Elkmann, F., Gruber, A., Lahmer, T., Mayr, U., Herner, A., Schellnegger, R., Schneider, J., Schmid, R. M., Ayoub, W., Samy, W., Esmat, A., Battah, A., Mukhtar, S., Mongkolpun, W., Cortés, D. Orbegozo, Cordeiro, C. P. R., Vincent, J. L., Creteur, J., Funcke, S., Groesdonk, H., Saugel, B., Wagenpfeil, G., Wagenpfeil, S., Reuter, D. A., Fernandez, M. M., Fernandez, R., Magret, M., González-Castro, A., Bouza, M. T., Ibañez, M., García, C., Balerdi, B., Mas, A., Arauzo, V., Añón, J. M., Ruiz, F., Ferreres, J., Tomás, R., Alabert, M., Tizón, A. I., Altaba, S., Llamas, N., Goligher, E C., Fan, E., Herridge, M., Vorona, S., Sklar, M., Dres, M., Rittayamai, N., Lanys, A., Urrea, C., Tomlinson, G., Reid, W. D., Rubenfeld, G. D., Kavanagh, B. P., Brochard, L. J., Ferguson, N. D., Neto, A. Serpa, de Abreu, M. Gama, Pelosi, P., Schultz, M. J., Guérin, C., Papazian, L., Reignier, J., Ayzac, L., Loundou, A., Forel, J. M., Rolland-Debord, C., Bureau, C., Poitou, T., Clavel, M., Perbet, S., Terzi, N., Kouatchet, A., Similowski, T., Demoule, A., Hunfeld, N., Trogrlic, Z., Ladage, S., Osse, R. J., Koch, B., Rietdijk, W., Devlin, J., van der Jagt, M., Picetti, E., Ceccarelli, P., Mensi, F., Malchiodi, L., Risolo, S., Rossi, I., Antonini, M. V., Servadei, F., Caspani, M. L., Roquilly, A., Lasocki, S., Seguin, P., Geeraerts, T., Perrigault, P. F., Dahyot-Fizelier, C., Paugam-Burtz, C., Cook, F., Cinotti, R., dit Latte, D. Demeure, Mahe, P. J., Fortuit, C., Feuillet, F., Asehnoune, K., Marzorati, C., Spina, S., Scaravilli, V., Vargiolu, A., Riva, M., Giussani, C., Sganzerla, E., Citerio, G., Barbadillo, S., de Molina, F. J. González, Álvarez-Lerma, F., Rodríguez, A., Zakharkina, T., Martin-Loeches, I., Matamoros, S., Povoa, P., Torres, A., Kastelijn, J., Hofstra, J. J., de Jong, M., Schultz, M., Sterk, P., Artigas, A., Bos, L. J., Moreau, A. S., Martin-Loeches, I., Povoa, P., Salluh, J., Rodriguez, A., Nseir, S., de Jong, E., van Oers, J. A., Beishuizen, A., Girbes, A. R. J., Nijsten, M. W. N., de Lange, D. W., Bonvicini, D., Labate, D., Benacchio, L., Olivieri, A., Pizzirani, E., Lopez-Delgado, J. C., Gonzalez-Romero, M., Fuentes-Mila, V., Berbel-Franco, D., Romera-Peregrina, I., Martinez-Pascual, A., Perez-Sanchez, J., Abellan-Lencina, R., Ávila-Espinoza, R. E., Moreno-Gonzalez, G., Sbraga, F., Griffiths, S., Grocott, M. P. W., Creagh-Brown, B., Doyle, J., Wilkerson, P., Soon, Y., Huddart, S., Dickinson, M., Riga, A., Zuleika, A., Miyamoto, K., Kawazoe, Y., Morimoto, T., Yamamoto, T., Fuke, A., Hashimoto, A., Koami, H., Beppu, S., Katayama, Y., Ito, M., Ohta, Y., Yamamura, H., Rygård, S. L., Holst, L B., Wetterslev, J., Johansson, P. I., Perner, A., Soliman, I. W., de Lange, D. W., van Dijk, D., van Delden, J. J. M., Cremer, O. L., Slooter, A. J. C., Peelen, L. M., McWilliams, D., Snelson, C., Neves, A. Das, Loudet, C. I., Busico, M., Vazquez, D., Villalba, D., Veronesi, M., Lischinsky, A., López, F. J. L., Mori, L. Benito, Plotnikow, G., Díaz, A., Giannasi, S., Hernandez, R., Krzisnik, L., Cecotti, C., Viola, L., Lopez, R., Sottile, J. P., Benavent, G., Estenssoro, E., Chen, C. M., Lai, C. C., Cheng, K. C., Chou, W., Chan, K. S., Roeker, L. E., Horkan, C. M., Gibbons, F. K., Christopher, K. B., Weijs, P. J. M., Mogensen, K. M., Rawn, J. D., Robinson, M. K., Christopher, K. B., Tang, Z., Qiu, C., Ouyang, B., Cai, C., Guan, X., Regueira, T., Cea, L., Carlos, S. Juan, Elisa, B., Puebla, C., Vargas, A., Poulsen, M. K., Thomsen, L. P., Kjærgaard, S., Rees, S. E., Karbing, D. S., Wollersheim, T., Frank, S., Müller, M. C., Carbon, N. M., Skrypnikov, V., Pickerodt, P. A., Falk, R., Mahlau, A., Weber-Carstens, S., Lee, A., Inglis, R., Morgan, R., Barker, G., Kamata, K., Abe, T., Saitoh, D., Tokuda, Y., Green, R. S., Butler, M. B., Erdogan, M., Hwa, H. Tae, Gil, L. Jae, Vaquero, R. Hernández, Rodriguez-Ruiz, E., Lago, A. Lopez, Allut, J. L. Garcia, Gestal, A. Estany, Gonzalez, M. A. Garcia, Thomas-Rüddel, D. O., Schwarzkopf, D., Fleischmann, C., Reinhart, K., Suwanpasu, S., Sattayasomboon, Y., Filho, N. M. Filgueiras, Oliveira, J. C. A., Ballalai, C. S., De Lucia, C. V., Araponga, G. P., Veiga, L. N., Silva, C. S., Garrido, M. E., Ramos, B. B., Ricaldi, E. F., Gomes, S. S., Gemmell, L., MacKay, A., Wright, C., Docking, R. I., Doherty, P., Black, E., Stenhouse, P., Plummer, M. P., Finnis, M. E., Phillips, L. K., Kar, P., Bihari, S., Biradar, V., Moodie, S., Horowitz, M., Shaw, J. E., Deane, A. M., Yatabe, T., Inoue, S., Sakaguchi, M., Egi, M., Abdelhamid, Y. Ali, Plummer, M. P., Finnis, M. E., Phillips, L. K., Kar, P., Bihari, S., Biradar, V., Moodie, S., Horowitz, M., Shaw, J. E., Deane, A. M., Hokka, M., Egi, M., Mizobuchi, S., Kar, P., Plummer, M., Abdelhamid, Y. Ali, Giersch, E., Summers, M., Hatzinikolas, S., Heller, S., Chapman, M., Jones, K., Horowitz, M., Deane, A., Schweizer, R., Jacquet-Lagreze, M., Portran, P., Junot, S., Allaouchiche, B., Fellahi, J. L., Guerci, P., Ergin, B., Kapucu, A., Ince, C., Cioccari, L., Luethi, N., Crisman, M., Bellomo, R., Mårtensson, J., Shinotsuka, C. Righy, Fagnoul, D., Brasseur, A., Orbegozo, D., Vincent, J. L., Preiser, J. C., Preiser, J. C., Lheureux, O., Thooft, A., Brimioulle, S., Vincent, J. L., Iwasaka, H., Tahara, S., Nagamine, M., Ichigatani, A., Cabrera, A. Rugerio, Zepeda, E. Monares, Granillo, J. Franco, Sánchez, J. S. Aguirre, Montoya, A. A. Tanaka, Montenegro, A. Pedraza, Blanco, G. A. Gálvez, Robles, C. M. Coronado, Drolz, A., Horvatits, T., Roedl, K., Rutter, K., Kluge, S., Funk, G. C., Schneeweiss, B., Fuhrmann, V., Sabetian, G., Pooresmaeel, F., Zand, F., Ghaffaripour, S., Farbod, A., Tabei, H., Taheri, L., Anandanadesan, R., Metaxa, V., Teixeira, C., Pereira, S. M., Hernández-Marrero, P., Carvalho, A. S., Beckmann, M., Hartog, C. S., Schwarzkopf, D., Raadts, A., Robertsen, A., Førde, R., Skaga, N. O., Helseth, E., Honeybul, S., Ho, K., Lopez, P. Martinez, Gonzalez, M. Nieto, Ortega, P. Nuevo, Sola, E. Camara, Spasova, T., de la Torre-Prados, M. V., Kopecky, O., Rusinova, K., Waldauf, P., Cepeplikova, Z., Balik, M., Domínguez, J. Palamidessi, Almudevar, P. Matia, Carmona, S. Alcántara, Muñoz, J. J. Rubio, Castañeda, D. Palacios, Abellán, A. Naharro, Villamizar, P. Rodríguez, Ramos, J. Veganzones, Pérez, L. Pérez, Lucendo, A. Pérez, Ejarque, M. Camós, Estella, A., Camps, V. Lopez, Martín, M. C., Masnou, N., Barbosa, S., Varela, A., Palma, I., Cristina, L., Nunes, E., Pereira, I., Campello, G., Granja, C., Pande, R., Pandey, M., Varghese, S., Chanu, M., Van Dam, M. J., Ter Braak, E. W. M. T., Estella, A., Gracia, M., Viciana, R., Recuerda, M., Fontaiña, L. Perez, Tharmalingam, B., Kovari, F., Rose, L., Mcginlay, M., Amin, R., Burns, K., Connolly, B., Hart, N., Jouvet, P., Katz, S., Leasa, D., Mawdsley, C., Mcauley, D., Schultz, M., Blackwood, B., Denham, S., Worrall, R., Arshad, M., Isherwood, P., Khadjibaev, A., Sabirov, D., Rosstalnaya, A., Parpibaev, F., Sharipova, V., Blanco, G. A. Galvez, Guzman, C. I. Olvera, Sánchez, J. S. Aguirre, Granillo, J. Franco, Gupta, S., Govil, D., Srinivasan, S., Patel, S. J., N, J. K., Gupta, A., Shafi, M., Tomar, D. S., Harne, R., Arora, D. P., Talwar, N., Mazumdar, S., Cha, Y. S., Lee, S. J., Tyagi, N., Rajput, R. K., Taneja, S., Singh, V. K., Sharma, S. C., Mittal, S., Rao, B. K., Ayachi, J., Fraj, N., Romdhani, S., Khedher, A., Meddeb, K., Sma, N., Azouzi, A., Bouneb, R., Chouchene, I., El Ghardallou, M., Boussarsar, M., Jennings, R., Walter, E., Ribeiro, J. M., Moniz, I., Marçal, R., Santos, A. C., Candeias, C., e Silva, Z. Costa, Gomez, S. E. Zamora, Nieto, O. R. Perez, Gonzalez, J. A. Castanon, Cuellar, A. I. Vasquez, Mildh, H., Pettilä, V., Korhonen, A. M., Karlsson, S., Ala-Kokko, T., Reinikainen, M., Vaara, S. T., Zaleska-Kociecka, M., Grabowski, M., Dąbrowski, M., Wozniak, S., Piotrowska, K., Banaszewski, M., Imiela, J., Stepinska, J., Pérez, A. González, Ordoñez, P. Florez, Giribet, A., Cuervo, M. A. Alonso, Cuervo, R. Alonso, Esteban, M. A. Rodriguez, Fraile, L. Iglesias, Mittelbrum, C. Ponte, Albaiceta, G. Muñiz, Koeze, J., Keus, F., Dieperink, W., van der Horst, I. C. C., van Meurs, M., Zijlstra, J. G., Roberts, S., Caballero, C. Hernandez, Isgro, G., Hall, D., Beitland, S., Trøseid, A.-M. S., Brusletto, B. S., Waldum-Grevbo, B. E., Berg, J. P., Sunde, K., Huertas, D. García, Manzano, F., Quintana, M. M. Jiménez-, Osuna, A., Santiago-Ruiz, F., Rodríguez-Mejías, C., Wangensteen, R., Jamaati, H. R., Masjedi, M., Zand, F., Hashemian, S. M. R., Sabetian, G., Abbasi, G., Khaloo, V., Tabei, S. H.a., Kafilzadeh, A., Bakhodaei, H. Haddad, Diaz, J. A., Silva, R., Garcia, D. J., Luis, E., Gomez, M. N., Soriano, R., Gonzalez, P. L., Ibrahim, I. A., Rafik, M. M., Al-Ansary, A. M., Algendi, M. A., Ali, A. A., Fuhrmann, V., Roedl, K., Horvatits, T., Drolz, A., Rutter, K., Benten, D., Kluwe, J., Siedler, S., Kluge, S., Adedugbe, I., Bird, G. T., Kennedy, R. M., Sharma, S., Butler, M. B., Yugi, G., Haroon, B. A., Witter, T., Khaliq, W., Singer, M., Havaldar, A. A., Krishna, B., Sriram, S., Espinoza, E. D. Valenzuela, Pozo, M. O., Edul, V. S. Kanoore, Furche, M., Motta, M. F., Vazquez, A. Risso, Birri, P. N. Rubatto, Ince, C., Dubin, A., Dogliotti, A., Ramos, A., Lovesio, C., Delile, E., Nevière, R., Thiébaut, P.-A., Maupoint, J., Mulder, P., Coquerel, D., Renet, S., do Rego, J. C., Rieusset, J., Richard, V., Tamion, F., Khaliq, W., Andreis, D. T., Singer, M., Smit, B., Smulders, Y. M., de Waard, M. C., van Straaten, H. M. Oudemans, Girbes, A. R. J., Eringa, E. C., Man, A. M. E. Spoelstra-de, Alegría, L., Soto, D., Luengo, C., Gomez, J., Jarufe, N., Bruhn, A., Castro, R., Kattan, E., Tapia, P., Rebolledo, R., Achurra, P., Ospina-Tascón, G., Bakker, J., Hernández, G., Bertini, P., Guarracino, F., Baldassarri, R., Pinsky, M. R., Alegría, L., Vera, M., Dreyse, J., Carpio, D., Henriquez, C., Gajardo, D., Bravo, S., Castro, R., Ospina-Tascón, G., Bakker, J., Hernández, G., Kim, S., Lee, M., Park, S. Y., So, S., Lee, H., Kačar, M. B., Kačar, S. M., Uddin, I., Belhaj, A. M., Aydın, M. A., Avsec, D., Kapuağası, A., Kaymak, Ç., Kovach, L., Şencan, İ., Meço, B., Özçelik, M., Ünal, N., Lazaridis, C., Jenni-Moser, B., Jeitziner, M.-M., Galassi, M. S., Sales, F. L., de Moraes, K. C. L., Batista, C. L., Júnior, J. A. de Souza, Marcari, T. B., Lobato, R., Castro, C. S. A. A., de Souza, L. M., Rodrigues, F. F. P., Correa, N. G., Pelegrini, A. M., Eid, R. A. C., Timenetsky, K. T., Cazati, D., Lobato, M., Diniz, P. S., Rocha, L. L., Cavalheiro, A. M., Lucinio, N. M., Santos, E. R., Norrenberg, M., Gleize, A., Preiser, J. C., Simón, I. Fernández, Carmona, S. Alcántara, Valhonrat, I. Lipperheide, Domínguez, J. Palamidessi, Abellán, A. Naharro, Almudévar, P. Matía, Dávila, F., Rubio, J. J., Ramos, A. J., Reina, Á. J. Roldán, López, N. Palomo, Pérez, M. Adriaensens, Apolo, D. X. Cuenca, Villén, L. Martín, López, F. M. Porras, García, I. Palacios, Izurieta, J. R. Naranjo, Guerrero, J. J. Egea, Calvert, S., Quint, M., Adeniji, K., Young, R., Shevill, D. 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Iglesias, Mittelbrum, C. Ponte, Albaiceta, G. Muñiz, Ampatzidou, F., Sileli, M., Kehagioglou, G., Madesis, A., Karaiskos, T., Moursia, C., Maleoglou, H., Leleki, K., Drossos, G., Uz, Z., Ince, Y., Papatella, R., Bulent, E., Guerci, P., Ince, C., De Mol, B., Vicka, V., Gineityte, D., Ringaitiene, D., Norkiene, I., Sipylaite, J., Möller, C., Fleischmann, C., Thomas-Rueddel, D. O., Vlasakov, V., Rochwerg, B., Theurer, P., Gattinoni, L., Reinhart, K., Hartog, C. S., Pérez, A. González, Al Sibai, J. Zanabili, Camblor, P. Martinez, Fernandez, P. Alvarez, Gala, J. M. García, Guisasola, J. Silba, Albaiceta, G. Muñiz, Tamura, T., Yatabe, T., Miyajima, I., Yamashita, K., Yokoyama, M., Ampatzidou, F., Kehagioglou, G., Dalampini, E., Nastou, M., Baddour, A., Ignatiadis, A., Asteri, T., Drossos, G., Hathorn, K. E., Purtle, S. W., Horkan, C. M., Gibbons, F. K., Christopher, K. B., Viana, M. V., Tonietto, T. A., Gross, L. A., Costa, V. L., Tavares, A. L. J., Lisboa, B. O., Moraes, R. B., Vieira, S. R., Viana, L. V., Azevedo, M. J., Ceniccola, G. D., Pequeno, R. S. F., Holanda, T. P., Mendonça, V. S., Araújo, W. M. C., Carvalho, L. S. F., Segaran, E., Vickers, L., Brinchmann, K., Wignall, I., Rubulotta, F., De Brito-Ashurst, I., del Olmo, R., Esteban, M. J., Vaquerizo, C., Carreño, R., Gálvez, V., Kaminsky, G., Nieto, B., Fuentes, M., De la Torre, M. A., Torres, E., Alonso, A., Velayos, C., Saldaña, T., Escribá, A., GRIP, J., Kölegård, R., Sundblad, P., Rooyackers, O., Naser, Ben, Jaziri, F., Jazia, A. Ben, Barghouth, M., Hentati, O., Skouri, W., El Euch, M., Mahfoudhi, M., Turki, S., Abdelghni, K. Ben, Abdallah, Ben, Maha, B. N. M., Cánovas, J., Sotos, F., López, A., Lorente, M., Burruezo, A., Torres, D., Polok, K., Włudarczyk, A., Górka, J., Hałek, A., Musiał, J., Szczeklik, W., Jazia, A. Ben, Jaziri, F., Bargouth, M., Bennasr, M., Turki, S., Abdelghani, K. Ben, Abdallah, T. Ben, de Grooth, H. J., Geenen, I. L., Parienti, J. J., Straaten, H. M. Oudemans-van, Shum, H. P., King, H. S., Chan, K. C., Yan, W. W., Londoño, J. Gonzalez, Cardenas, C. Lorencio, Pedrosa, M. Morales, Gubianas, C. Murcia, Bertolin, C. Fuster, Batllori, N. Vila, Sirvent, J. M., Wykes, K., Jack, J., Morgan, P., Mukhopadhyay, A., Chan, H. Y., Kowitlawakul, Y., Remani, D., Leong, C. S. F., Henry, C. J., Puthucheary, Z. A., Mendsaikhan, N., Begzjav, T., Lundeg, G., Dünser, M., Espinoza, E. D. Valenzuela, Welsh, S. P., Motta, M. F., Guerra, E., Zerpa, M. C. l., Zechner, F., Furche, M., Berdaguer, F., Birri, P. N. Rubatto, Risso-Vazquez, A., Dubin, A., Masevicius, F. D., Greaney, D., Magee, A., Fitzpatrick, G., Lugo-Cob, R. G., Sánchez-Hurtado, L. A., Arvizu-Tachiquín, P. C., Tejeda-Huezo, B. C., Cano-Oviedo, A. A., Baltazar-Torres, J. A., Aydogan, M. S., Togal, T., Taha, A., Chai, H. Z., Kam, C., Razali, S. S. Yang, Sivasamy, V., Kuan, L. Y., Poulose, V., Morales, M. A. Lopez, Castro, S., Pires, T., Melão, L., Krystopchuk, A., Pereira, I., Granja, C., Taniguchi, L. U., Pires, E. M. C., Vieira, Jr, J. M., Azevedo, L. C. P., Nurses of the Central and General ICUs of Shiraz Namazi Hospital, Sedation an Delirium Group Hospital Universitari de Bellvitge, SPACeR group (Surrey Peri-operative, Anaesthesia and Critical Care Collaborative Research Group), for the PRoVENT investigators and the PROVE Network, SEMICYUC/GETGAG Working Group, TAVeM study group, POPC-CB investigators, DESIRE (DExmedetomidine for Sepsis in ICU Randomized Evaluation) Trial Investigators, GEMINI, Bioethics work group of SEMICYUC, The FINNAKI Study Group, Queen Square Neuroanaesthesia and Neurocritical Care Resreach Group, Renal Transplantation HUVR, GEMINI, EDISVAL Group, EDISVAL Group, PLUG Working group, TAVeM study Group, The FINNAKI Study Group, on behalf of Department of Professional Development, ESICM, Critical Care Research Group, SIRAKI group, and Grupo ESBAGA

Published
2016
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5. The consensus molecular subtypes in translation

Author

ten Hoorn, S., Vermeulen, Louis, Punt, Cornelis, Koens, Lianne, Medema, Jan Paul, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, CCA - Imaging and biomarkers, CCA - Cancer biology and immunology, Center of Experimental and Molecular Medicine, Graduate School, Vermeulen, L., Punt, C.J.A., Koens, L., Medema, J.P., and Faculteit der Geneeskunde

Abstract

Colorectal cancer (CRC) is a major health care burden and one of the main causes of mortality. CRC is a heterogeneous disease, with patients presenting with different histopathological features, genetic mutations, course of the disease and response to treatment. The current clinicopathological characteristics combined with a few molecular features to guide treatment for CRC is insufficient in predicting prognosis and therapy response for the individual patient. This is leading to substantial over- and undertreatment in a large proportion of patients. Additional molecular tumor characteristics are needed to achieve a personalized approach with a treatment plan tailored for each patient. The consensus molecular subtypes (CMSs) provide a stratification of CRC into molecularly highly distinct subtypes (CMS1-4). Although the CMSs were principally founded on the basis of differences in tumor biology, they also contain important clinical information as each subtype shows a different prognosis and distinct response to various treatment regimens. In this thesis we explored the potential and therapeutic implications in clinical practice of the CMSs. We show the great potential of the CMSs to guide treatment allocation in future clinical practice. Although not completely ready for the clinic yet, once the findings are sufficiently validated in prospective clinical trials the CMS or related classification systems will have an important impact on improving and tailoring treatment strategies for the individual CRC patient. Therefore, the path towards clinical implementation should already be developed.

Published
2022

6. Interconnectivity between molecular subtypes and tumor stage in colorectal cancer

Author

Coebergh van den Braak, R.R.J. (Robert), Ten Hoorn, S. (S.), Sieuwerts, A.M. (Anieta), Tuynman, J.B., Smid, M. (Marcel), Wilting, S.M. (Saskia), Martens, J.W.M. (John), Punt, C.J.A. (Cornelis), Foekens, J.A. (John), Medema, J.P. (Jan Paul), IJzermans, J.N.M. (Jan), Vermeulen, L. (L.), Coebergh van den Braak, R.R.J. (Robert), Ten Hoorn, S. (S.), Sieuwerts, A.M. (Anieta), Tuynman, J.B., Smid, M. (Marcel), Wilting, S.M. (Saskia), Martens, J.W.M. (John), Punt, C.J.A. (Cornelis), Foekens, J.A. (John), Medema, J.P. (Jan Paul), IJzermans, J.N.M. (Jan), and Vermeulen, L. (L.)

Abstract

BACKGROUND: There are profound individual differences in clinical outcomes between colorectal cancers (CRCs) presenting with identical stage of disease. Molecular stratification, in conjunction with the traditional TNM staging, is a promising way to predict patient outcomes. We investigated the interconnectivity between tumor stage and tumor biology reflected by the Consensus Molecular Subtypes (CMSs) in CRC, and explored the possible value of these insights in patients with stage II colon cancer. METHODS: We performed a retrospective analysis using clinical records and gene expression profiling in a meta-cohort of 1040 CRC patients. The interconnectivity of tumor biology and disease stage was assessed by investigating the association between CMSs and TNM classification. In order to validate the clinical applicability of our findings we employed a meta-cohort of 197 stage II colon cancers. RESULTS: CMS4 was significantly more prevalent in advanced stages of disease (stage I 9.8% versus stage IV 38.5%, p < 0.001). The observed differential gene expression between cancer stages is at least partly explained by the biological differences as reflected by CMS subtypes. Gene signatures for stage III-IV and CMS4 were highly correlated (r = 0.77, p < 0.001). CMS4 cancers showed an increased progression rate to more advanced stages (CMS4 compared to CMS2: 1.25, 95% CI: 1.08-1.46). Patients with a CMS4 cancer had worse survival in the high-risk stage II tumors compared to the total stage II cohort (5-year DFS 41.7% versus 100.0%, p = 0.008). CONCLUSIONS: Considerable interconnectivity between tumor biology and tumor stage in CRC exists. This implies that the TNM stage, in addition to the stage of progression, might also reflect distinct biological disease entities. These insights can potentially be utilized to optimize identification of high-risk stage II colon

Published
2020
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8. Intracerebral hemorrhage in ICU: is it worth treating?

Author

Sivakumar, S, Taccone, F, Desai, K, Lazaridis, C, Skarzynski, M, Sekhon, M, Henderson, W, Griesdale, D, Chapple, L, Deane, A, Williams, L, Strickland, R, Lange, K, Heyland, D, Chapman, M, Rowland, M, Garry, P, Westbrook, J, Corkill, R, Antoniades, C, Pattinson, K, Fatania, G, Strong, A, Myers, R, Jermaine, C, Robertson, C, Rusin, C, Hofmeijer, J, Sondag, L, Tjepkema Cloostermans, M, Beishuizen, A, Bosch, F, van Putten, M, Carteron, L, Patet, C, Solari, D, Oddo, M, Ali, M, Dias, C, Almeida, R, Vaz Ferreira, A, Silva, J, Monteiro, E, Cerejo, A, Rocha, A, Elsayed, A, Abougabal, A, Beshey, B, Alzahaby, K, Pozzebon, S, Ortiz, A, Cristallini, S, Lheureux, O, Brasseur, A, Vincent, J, Creteur, J, Hravnak, M, Yousef, K, Chang, Y, Crago, E, Friedlander, R, Abdelmonem, S, Tahon, S, Helmy, T, Meligy, H, Puig, F, Dunn Siegrist, I, Pugin, J, Gupta, S, Govil, D, Srinivasan, S, Patel, S, N, J, Gupta, A, Tomar, D, Shafi, M, Harne, R, Arora, D, Talwar, N, Mazumdar, S, Papakrivou, E, Makris, D, Manoulakas, E, Tsolaki, B, Karadodas, B, Zakynthinos, E, Garcia, I, Martin, A, Encinares, V, Ibañez, M, Montero, J, Labrador, G, Cangueiro, T, Poulose, V, Koh, J, Kam, J, Yeter, H, Kara, A, Aktepe, O, Topeli, A, Tsolakoglou, I, Intas, G, Stergiannis, P, Kolaros, A, Chalari, E, Athanasiadou, E, Martika, A, Fildisis, G, Faivre, V, Mengelle, C, Favier, B, Payen, D, Poppe, A, Winkler, M, Mudersbach, E, Schreiber, J, Wruck, M, Schwedhelm, E, Kluge, S, Zöllner, C, Tavladaki, T, Spanaki, A, Dimitriou, H, Kondili, E, Choulaki, C, Meleti, E, Kafetzopoulos, D, Georgopoulos, D, Briassoulis, G, la Torre, A, de la Torre Prados, M, Tsvetanova Spasova, T, Nuevo Ortega, P, Rueda Molina, C, Fernández Porcel, A, Camara Sola, E, Salido Díaz, L, García Alcántara, A, Meleti, D, Suberviola, B, Riera, J, Rellan, L, Sanchez, M, Robles, J, Lopez, E, Vicente, R, Miñambres, E, Santibañez, M, Le Guen, M, Moore, J, Mason, N, Windpassinger, M, Plattner, O, Mascha, E, Sessler, D, Research, O, Melia, U, Fontanet, J, van den Berg, J, Struys, M, Vereecke, H, Jensen, E, Rood, P, van de Schoor, F, van Tertholen, K, Pickkers, P, van den Boogaard, M, Beardow, Z, Redhead, H, Paramasivam, K, Numan, T, Kamper, A, Peelen, L, Zeman, P, Slooter, A, van Ewijk, C, Jacobs, G, Girbes, A, Myatra, S, Harish, M, Prabu, N, Siddiqui, S, Kulkarni, A, Divatia, J, Murbach, L, Leite, M, Osaku, E, Costa, C, Pelenz, M, Neitzke, N, Moraes, M, Jaskowiak, J, Silva, M, Zaponi, R, Abentroth, L, Ogasawara, S, Jorge, A, Duarte, P, Hernández Sánchez, N, Sánchez Hurtado, L, García Guillen, F, Ñamendys Silva, S, Maghsoudi, B, Emami, M, Khosravi, M, Zand, F, Tabatabaie, H, Masjedi, M, Sabetiyan, G, Mokri, A, Troubleyn, J, Diltoer, M, Jacobs, R, Nguyen, D, De Waele, E, De Regt, J, Honoré, P, Van Gorp, V, Spapen, H, Contreras, R, Toapanta, N, Moreno, G, Sabater, J, Torrado, H, Gonzalez, M, Marin, M, Farigola, E, Gonzalez, A, Fernandez, J, Vera, A, Gisbert, X, Juliá, C, Uya, J, Corral, L, Elias Jones, I, Gemmell, L, Mackay, A, Randall, D, Adwaney, A, Blunden, M, Prowle, J, Kirwan, C, Thomas, N, Owen, H, Darwin, L, Conway, D, Atkinson, D, Sharman, M, Barbanti, C, Amour, J, Gaudard, P, Rozec, B, Mauriat, P, M'Rini, M, Leger, P, Cambonie, G, Liet, J, Girard, C, Laroche, S, Damas, P, Assaf, Z, Loron, G, Lecourt, L, Pouard, P, Kim, S, Na, S, Kim, J, Oh, S, Jung, C, Yoo, S, Min, S, Chung, E, Lee, H, Lee, N, Lee, K, Suh, K, Ryu, H, Marshall, D, Goodson, R, Salciccioli, J, Shalhoub, J, Potter, E, Kirk Bayley, J, Karanjia, N, Forni, L, Creagh Brown, B, Bossy, M, Nyman, M, Tailor, A, D'Antini, D, Spadaro, S, Valentino, F, Sollitto, F, Cinnella, G, Mirabella, L, Calvo, F, Bejarano, N, Padilla, D, Baladron, V, Villajero, P, Villazala, R, Redondo, J, Yuste, A, Liu, J, Shen, F, Teboul, J, Anguel, N, Beurton, A, Bezaz, N, Richard, C, Monnet, X, Fossali, T, Colombo, R, Ottolina, D, Rossetti, M, Mazzucco, C, Marchi, A, Porta, A, Catena, E, Tollisen, K, Andersen, G, Heyerdahl, F, Jacobsen, D, de Waard, M, van IJzendoorn, M, Buter, H, 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Laisne, L, Rabbat, A, Lebert, C, Perez, P, Chaize, M, Renault, A, Meert, A, Hamidfar, R, Jourdain, M, Darmon, M, Schlemmer, B, Chevret, S, Lemiale, V, Azoulay, E, Benoit, D, Martins Branco, D, Sousa, M, Marum, S, Bouw, M, Galstyan, G, Makarova, P, Parovichnikova, E, Kuzmina, L, Troitskaya, V, Drize, N, Gemdzhian, E, Savchenko, V, Chao, H, Kılıc, E, Demiriz, B, Uygur, M, Sürücü, M, Cınar, K, Yıldırım, A, Kiss, K, Köves, B, Csernus, V, Molnár, Z, Ntantana, A, Matamis, D, Savvidou, S, Giannakou, M, Gouva, M, Nakos, G, Koulouras, V, Gaffney, S, Judge, C, Drew, T, Misran, H, Munshi, R, Mcgovern, L, Coyle, M, Dunne, L, Deasy, E, Lavin, P, Fahy, A, Darcy, D, Donnelly, M, Ismail, N, Hall, T, Wykes, K, Jack, J, Ngu, W, Morgan, P, Ruiz Ramos, J, Ramirez, P, Gordon, M, Villarreal, E, Frasquet, J, Poveda Andrés, J, Castellanos, A, Ijssennagger, C, Ten Hoorn, S, van Wijk, A, van den Broek, J, Tuinman, P, Elmenshawy, A, Hammond, B, Gibbon, G, Belcham, T, Burton, K, Taniguchi, L, Ramos, F, Momma, A, 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Rosenqvist, M, Melander, O, Chew, M, Kishihara, Y, Yasuda, H, Jimenez, R, Torrella, P, Fernandez, A, Sanchez, S, Ortin, A, Prats, R, Aguilera, E, Marti, D, Fernandez, L, Ferrer, M, Lanziotti, V, Pulcheri, L, Ribeiro, M, Barbosa, A, E. Silva, J, Soares, M, Marqués, M, Moreno, A, Pizarraya, A, Smani, Y, Connell, M, Zhang, L, Parker, R, Banerjee, I, Clermont, G, Norberg, E, Oras, J, Cuisinier, A, Maufrais, C, Payen, J, Nottin, S, Walther, G, Arib, S, Bilotta, F, Badenes, R, Rubulotta, F, Mirek, S, Monfort, B, Stazi, E, Roig, A, Magnoni, S, Marando, M, Pifferi, S, Conte, V, Ortolano, F, Carbonara, M, Bertani, G, Scola, E, Cadioli, M, Triulzi, F, Colombo, A, Stocchetti, N, Rotzel, H, Lázaro, A, Prada, D, Guimillo, M, Piqueras, C, Guia, J, Simon, M, Arizmendi, A, Carratalá, A, El Maraghi, S, Yehia, A, Bakry, M, Shoman, A, Backes, F, Bianchin, M, Vieira, S, de Souza, A, Backes, A, Klein, C, Arunkumar, A, Lozano, A, Gallaher, C, Cattlin, S, Gordon, S, Picard, J, Fontana, V, Bond, O, Nobile, L, Mrozek, S, Delamarre, L, Capilla, F, Al Saati, T, Fourcade, O, Dominguez Berrot, A, Gonzalez Vaquero, M, Vallejo Pascual, M, Gupta, D, Ivory, B, Chopra, M, Mccarthy, J, Felderhof, C, Macneil, C, Maggiorini, M, Duska, F, Fumis, R, Junior, J, Amarante, G, Skorko, A, Sanders, S, Aron, J, Kroll, R, Redfearn, C, Krishnan, P, Khalil, J, Kongpolprom, N, Gulia, V, Lourenço, E, Duro, C, Baptista, G, Alves, A, Arminda, B, Rodrigues, M, Hayward, J, Baldwin, F, Gray, R, Katinakis, P, Stijf, M, Ten Kleij, M, Jansen Frederiks, M, Broek, R, de Bruijne, M, Spronk, P, Sinha, K, Luney, M, Palmer, K, Keating, L, Abu Habsa, M, Bahl, R, Baskaralingam, N, Ahmad, A, Kanapeckaite, L, Bhatti, P, Glace, S, Jeyabraba, S, Lewis, H, Kostopoulos, A, Raja, M, West, A, Ely, A, Turkoglu, L, Zolfaghari, P, Baptista, J, Marques, M, Martins, P, Pimentel, J, Su, Y, Villacres, S, Stone, M, Parsikia, A, Medar, S, O'Dea, K, Porter, J, Tirlapur, N, Jonathan, J, Singh, S, Takata, M, Mcwhirter, E, Lyon, R, Hariz, M, Azmi, E, Alkhan, J, Movsisyan, V, Petrikov, S, Marutyan, Z, Aliev, I, Evdokimov, A, Antonucci, E, Merz, T, Hartmann, C, Calzia, E, Radermacher, P, Nußbaum, B, Huber Lang, M, Gröger, M, Svoren Jabalera, E, Davenport, E, Humburg, P, Knight, J, Hinds, C, Jun, I, Kim, W, Besch, G, Perrotti, A, Puyraveau, M, Baltres, M, Samain, E, Chocron, S, Pili Floury, S, Plata Menchaca, E, Sabater Riera, J, Estruch, M, Boza, E, Toscana Fernández, J, Bruguera Pellicer, E, Ordoñez Llanos, J, Pérez Fernández, X, Cavaleiro, P, Tralhão, A, Arrigo, M, Lopes, J, Lebrun, M, Cholley, B, Perezvela, J, Marinmateos, H, Rivera, J, Llorente, M, De Marcos, B, Fernandez, F, Laborda, C, Zamora, D, Delgado, J, Imperiali, C, Dastis, M, Górka, J, Górka, K, Iwaniec, T, Frołow, M, Polok, K, Fronczek, J, Kózka, M, Musiał, J, Szczeklik, W, Sileli, M, Moursia, C, Maleoglou, H, Leleki, K, Uz, Z, Ince, Y, Papatella, R, Bulent, E, De Mol, B, Vicka, V, Gineityte, D, Ringaitiene, D, Norkiene, I, Sipylaite, J, Möller, C, Thomas Rueddel, D, Vlasakov, V, Rochwerg, B, Theurer, P, Al Sibai, J, Camblor, P, Fernandez, P, Gala, J, Guisasola, J, Tamura, T, Miyajima, I, Yamashita, K, Yokoyama, M, Dalampini, E, Nastou, M, Baddour, A, Ignatiadis, A, Asteri, T, Hathorn, K, Purtle, S, Viana, M, Tonietto, T, Gross, L, Costa, V, Tavares, A, Lisboa, B, Moraes, R, Viana, L, Azevedo, M, Ceniccola, G, Pequeno, R, Holanda, T, Mendonça, V, Araújo, W, Carvalho, L, Segaran, E, Vickers, L, Brinchmann, K, Wignall, I, De Brito Ashurst, I, Del Olmo, R, Vaquerizo, C, Carreño, R, Gálvez, V, Kaminsky, G, Nieto, B, Fuentes, M, De la Torre, M, Torres, E, Alonso, A, Velayos, C, Saldaña, T, Escribá, A, Grip, J, Kölegård, R, Sundblad, P, Rooyackers, O, Naser, B, Jaziri, F, Jazia, A, Barghouth, M, Hentati, O, Skouri, W, El Euch, M, Mahfoudhi, M, Turki, S, Abdelghni, K, Abdallah, B, Maha, B, Lorente, M, Włudarczyk, A, Hałek, A, Bargouth, M, Bennasr, M, Abdelghani, K, Abdallah, T, Geenen, I, Parienti, J, Shum, H, King, H, Yan, W, Londoño, J, Cardenas, C, Pedrosa, M, Gubianas, C, Bertolin, C, Batllori, N, Sirvent, J, Mukhopadhyay, A, Chan, H, Kowitlawakul, Y, Remani, D, Leong, C, Henry, C, Puthucheary, Z, Mendsaikhan, N, Begzjav, T, Lundeg, G, Dünser, M, Welsh, S, Guerra, E, Zerpa, M, Zechner, F, Berdaguer, F, Risso Vazquez, A, Masevicius, F, Greaney, D, Magee, A, Fitzpatrick, G, Lugo Cob, R, Tejeda Huezo, B, Cano Oviedo, A, Aydogan, M, Togal, T, Taha, A, Chai, H, Kam, C, Razali, S, Sivasamy, V, Kuan, L, Morales, M, Pires, T, and Azevedo, L

Subjects
intracerebral haemorrhage in intensive care
Published
2016

9. ESICM LIVES 2016: part two

Author

Sivakumar, S., Taccone, F. S., Desai, K. A., Lazaridis, C., Skarzynski, M., Sekhon, M., Henderson, W., Griesdale, D., Chapple, L., Deane, A., Williams, L., Strickland, R., Lange, K., Heyland, D., Chapman, M., Rowland, M. J., Garry, P., Westbrook, J., Corkill, R., Antoniades, C. A., Pattinson, K. T., Fatania, G., Strong, A. J., Myers, R. B., Jermaine, C. M., Robertson, C. S., Rusin, C. G., Hofmeijer, J., Sondag, L., Tjepkema-Cloostermans, M. C., Beishuizen, A., Bosch, F. H., van Putten, M. J. A. M., Carteron, L., Patet, C., Solari, D., Oddo, M., Ali, M. A., Dias, C., Almeida, R., Vaz-Ferreira, A., Silva, J., Monteiro, E., Cerejo, A., Rocha, A. P., Elsayed, A. A., Abougabal, A. M., Beshey, B. N., Alzahaby, K. M., Pozzebon, S., Ortiz, A. Blandino, Cristallini, S., Lheureux, O., Brasseur, A., Vincent, J. L., Creteur, J., Hravnak, M., Yousef, K., Chang, Y., Crago, E., Friedlander, R. M., Abdelmonem, S. A., Tahon, S. A., Helmy, T. A., Meligy, H. S., Puig, F., Dunn-Siegrist, I., Pugin, J., Gupta, S., Govil, D., Srinivasan, S., Patel, S. J., N, J. K., Gupta, A., Tomar, D. S., Shafi, M., Harne, R., Arora, D. P., Talwar, N., Mazumdar, S., Papakrivou, E. E., Makris, D., Manoulakas, E., Tsolaki, B., Karadodas, B., Zakynthinos, E., Garcia, I. Palacios, Martin, A. Diaz, Encinares, V. Sanchez, Ibañez, M. Pachón, Montero, J. Garnacho, Labrador, G., Cangueiro, T. Cebrero, Poulose, V., Koh, J., Kam, J. W., Yeter, H., Kara, A., Aktepe, O., Topeli, A., Tsolakoglou, I., Intas, G., Stergiannis, P., Kolaros, A. A., Chalari, E., Athanasiadou, E., Martika, A., Fildisis, G., Faivre, V., Mengelle, C., Favier, B., Payen, D., Poppe, A., Winkler, M. S., Mudersbach, E., Schreiber, J., Wruck, M. L., Schwedhelm, E., Kluge, S., Zöllner, C., Tavladaki, T., Spanaki, A. M., Dimitriou, H., Kondili, E., Choulaki, C., Meleti, E., Kafetzopoulos, D., Georgopoulos, D., Briassoulis, G., la Torre, A. García-de, de la Torre-Prados, M. V., Tsvetanova-Spasova, T., Nuevo-Ortega, P., Rueda-Molina, C., Fernández-Porcel, A., Camara-Sola, E., Salido-Díaz, L., García-Alcántara, A., Meleti, D. E., Suberviola, B., Riera, J., Rellan, L., Sanchez, M., Robles, J. C., Lopez, E., Vicente, R., Miñambres, E., Santibañez, M., Le Guen, M., Moore, J., Mason, N., Windpassinger, M., Plattner, O., Mascha, E., Sessler, D. I., Research, Outcomes, Melia, U., Fontanet, J., van den Berg, J. P., Struys, M. M. R. F., Vereecke, H. E. M., Jensen, E. W., Rood, P. J. T., van de Schoor, F., van Tertholen, K., Pickkers, P., van den Boogaard, M., Beardow, Z. J., Redhead, H., Paramasivam, K., Numan, T., Kamper, A. M., Rood, P., Peelen, L. M., Zeman, P. M., Slooter, A. J., van Ewijk, C. E., Jacobs, G. E., Girbes, A. R. J., Myatra, S. N., Harish, M. M., Prabu, N. R., Siddiqui, S., Kulkarni, A. P., Divatia, J. V., Murbach, L. D., Leite, M. A., Osaku, E. F., Costa, C. R. L. M., Pelenz, M., Neitzke, N. M., Moraes, M. M., Jaskowiak, J. L., Silva, M. M. M., Zaponi, R. S., Abentroth, L. R. L., Ogasawara, S. M., Jorge, A. C., Duarte, P. A. D., Hernández-Sánchez, N., Sánchez-Hurtado, L. A., García-Guillen, F. J., Ñamendys-Silva, S. A., Maghsoudi, B., Emami, M., Khosravi, M. B., Zand, F., Tabatabaie, H. R., Masjedi, M., Sabetiyan, G., Mokri, A., Troubleyn, J., Diltoer, M., Jacobs, R., Nguyen, D. N., De Waele, E., De Regt, J., Honoré, P. M., Van Gorp, V., Spapen, H. D., Contreras, R. S., Toapanta, N. D., Moreno, G., Sabater, J., Torrado, H., Gonzalez, M., Marin, M., Farigola, E., Gonzalez, A., Fernandez, J., Vera, A., Gisbert, X., Juliá, C., Uya, J., Corral, L., Elias-Jones, I., Gemmell, L., MacKay, A., Randall, D., Adwaney, A., Blunden, M., Prowle, J. R., Kirwan, C. J., Thomas, N., Martin, A., Owen, H., Darwin, L., Conway, D., Atkinson, D., Sharman, M., Barbanti, C., Amour, J., Gaudard, P., Rozec, B., Mauriat, P., M’rini, M., Leger, P. L., Cambonie, G., Liet, J. 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W., Hoekstra, M., Sterz, F., Horvatits, K., Herkner, H., Kott, M., Zitta, K., Brandt, B., Schildhauer, C., Elke, G., Hummitzsch, L., Albrecht, M., González, L. Rey, Alonso, D. Cabestrero, Sánchez, R. de Pablo, Lucas, J. Higuera, Ferlitsch, A., Fauler, G., Trauner, M., Pischke, S., Fischer, L., Thaiss, F., Koch, M., Bangert, K., Lohse, A. W., Nashan, B., Sterneck, M., Faenza, S., Siniscalchi, A., Pierucci, E., Mancini, E., Ricci, D., Gemelli, C., Cuoghi, A., Magnani, S., Atti, M., Sotos, F., Cánovas, J., López, A., Burruezo, A., Torres, D., Herrera-Gutierrez, M. E., Barrueco-Francioni, J., Arias-Verdú, D., Lozano-Saez, R., Quesada-Garcia, G., Seller-Pérez, G., Figueiredo, A., Anzola, Y., Pereira, R., Bento, L., Lai, M., Deiana, M., Seller-Perez, G., Vardas, K., Ilia, S., Sertedaki, A., Charmadari, E., Stratakis, C. A., Briassouli, E., Goukos, D., Psarra, K., Botoula, E., Tsagarakis, S., Mageira, E., Routsi, C., Nanas, S., Campello, E., Radu, C. M., Su, H., Lam, Y. 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F., Nottin, S., Walther, G., Arib, S., Bilotta, F., Badenes, R., Rubulotta, F., Mirek, S., Monfort, B., Stazi, E., Roig, A. Lozano, Magnoni, S., Marando, M., Pifferi, S., Conte, V., Ortolano, F., Carbonara, M., Bertani, G., Scola, E., Cadioli, M., Triulzi, F., Colombo, A., Stocchetti, N., Rotzel, H. B., Lázaro, A. Serrano, Prada, D. Aguillón, Guimillo, M. Rodriguez, Piqueras, C. Sanchís, Guia, J. Romero, Simon, M. García, Arizmendi, A. Mesejo, Carratalá, A., El Maraghi, S., Yehia, A., Bakry, M., Shoman, A., Backes, F. N., Bianchin, M. M., Vieira, S. R. R., de Souza, A., Backes, A. N., Klein, C., Arunkumar, A. S., Lozano, A., Gallaher, C., Cattlin, S., Gordon, S., Picard, J., Fontana, V., Bond, O., Nobile, L., Mrozek, S., Delamarre, L., Capilla, F., Al-Saati, T., Fourcade, O., Dominguez-Berrot, A. M., Gonzalez-Vaquero, M., Vallejo-Pascual, M. E., Gupta, D., Ivory, B. D., Chopra, M., McCarthy, J., Felderhof, C. L., MacNeil, C., Maggiorini, M., Duska, F., Fumis, R. R. L., Junior, J. M. Vieira, Amarante, G., Skorko, A., Sanders, S., Aron, J., Kroll, R. J., Redfearn, C., Krishnan, P., Khalil, J. E., Kongpolprom, N., Gulia, V., Lourenço, E., Duro, C., Baptista, G., Alves, A., Arminda, B., Rodrigues, M., Hayward, J., Baldwin, F., Gray, R., Katinakis, P. A., Stijf, M., Ten Kleij, M., Jansen-Frederiks, M., Broek, R., de Bruijne, M., Spronk, P. E., Sinha, K., Luney, M., Palmer, K., Keating, L., Abu-Habsa, M., Bahl, R., Baskaralingam, N., Ahmad, A., Kanapeckaite, L., Bhatti, P., Glace, S., Jeyabraba, S., Lewis, H. F., Kostopoulos, A., Raja, M., West, A., Ely, A., Turkoglu, L. M., Zolfaghari, P., Baptista, J. P., Marques, M. P., Martins, P., Pimentel, J., Su, Y. C., Villacres, S., Stone, M. E., Parsikia, A., Medar, S., O’Dea, K. P., Porter, J., Tirlapur, N., Jonathan, J. M., Singh, S., Takata, M., McWhirter, E., Lyon, R., Hariz, M. L., Azmi, E., Alkhan, J., Movsisyan, V., Petrikov, S., Marutyan, Z., Aliev, I., Evdokimov, A., Antonucci, E., Merz, T., Hartmann, C., Calzia, E., Radermacher, P., Nußbaum, B., Huber-Lang, M., Gröger, M., Svoren-Jabalera, E., Davenport, E. E., Humburg, P., Knight, J., Hinds, C. J., Jun, I. J., Kim, W. J., Lee, E. H., Besch, G., Perrotti, A., Puyraveau, M., Baltres, M., Samain, E., Chocron, S., Pili-Floury, S., Plata-Menchaca, E. P., Sabater-Riera, J., Estruch, M., Boza, E., Toscana-Fernández, J., Bruguera-Pellicer, E., Ordoñez-Llanos, J., Pérez-Fernández, X. L., Cavaleiro, P., Tralhão, A., Arrigo, M., Lopes, J.-P., Lebrun, M., Cholley, B., PerezVela, J. L., MarinMateos, H., Rivera, J. J. Jimenez, Llorente, M. A. Alcala, De Marcos, B. Gonzalez, Fernandez, F. J. Gonzalez, Laborda, C. Garcia, Zamora, D. Fernandez, Delgado, J. C. Lopez, Imperiali, C., Dastis, M., Górka, J., Górka, K., Iwaniec, T., Frołow, M., Polok, K., Fronczek, J., Kózka, M., Musiał, J., Szczeklik, W., Sileli, M., Moursia, C., Maleoglou, H., Leleki, K., Uz, Z., Ince, Y., Papatella, R., Bulent, E., De Mol, B., Vicka, V., Gineityte, D., Ringaitiene, D., Norkiene, I., Sipylaite, J., Möller, C., Thomas-Rueddel, D. O., Vlasakov, V., Rochwerg, B., Theurer, P., Al Sibai, J. Zanabili, Camblor, P. Martinez, Fernandez, P. Alvarez, Gala, J. M. García, Guisasola, J. Silba, Tamura, T., Miyajima, I., Yamashita, K., Yokoyama, M., Dalampini, E., Nastou, M., Baddour, A., Ignatiadis, A., Asteri, T., Hathorn, K. E., Purtle, S. W., Viana, M. V., Tonietto, T. A., Gross, L. A., Costa, V. L., Tavares, A. L. J., Lisboa, B. O., Moraes, R. B., Vieira, S. R., Viana, L. V., Azevedo, M. J., Ceniccola, G. D., Pequeno, R. S. F., Holanda, T. P., Mendonça, V. S., Araújo, W. M. C., Carvalho, L. S. F., Segaran, E., Vickers, L., Brinchmann, K., Wignall, I., De Brito-Ashurst, I., del Olmo, R., Esteban, M. J., Vaquerizo, C., Carreño, R., Gálvez, V., Kaminsky, G., Nieto, B., Fuentes, M., De la Torre, M. A., Torres, E., Alonso, A., Velayos, C., Saldaña, T., Escribá, A., GRIP, J., Kölegård, R., Sundblad, P., Rooyackers, O., Naser, Ben, Jaziri, F., Jazia, A. Ben, Barghouth, M., Hentati, O., Skouri, W., El Euch, M., Mahfoudhi, M., Turki, S., Abdelghni, K. Ben, Abdallah, Ben, Maha, B. N. M., Lorente, M., Włudarczyk, A., Hałek, A., Bargouth, M., Bennasr, M., Abdelghani, K. Ben, Abdallah, T. Ben, Geenen, I. L., Parienti, J. J., Straaten, H. M. Oudemans-van, Shum, H. P., King, H. S., Chan, K. C., Yan, W. W., Londoño, J. Gonzalez, Cardenas, C. Lorencio, Pedrosa, M. Morales, Gubianas, C. Murcia, Bertolin, C. Fuster, Batllori, N. Vila, Sirvent, J. M., Mukhopadhyay, A., Chan, H. Y., Kowitlawakul, Y., Remani, D., Leong, C. S. F., Henry, C. J., Puthucheary, Z. A., Mendsaikhan, N., Begzjav, T., Lundeg, G., Dünser, M., Welsh, S. P., Guerra, E., Zerpa, M. C. l., Zechner, F., Berdaguer, F., Risso-Vazquez, A., Masevicius, F. D., Greaney, D., Magee, A., Fitzpatrick, G., Lugo-Cob, R. G., Tejeda-Huezo, B. C., Cano-Oviedo, A. A., Aydogan, M. S., Togal, T., Taha, A., Chai, H. Z., Kam, C., Razali, S. S. Yang, Sivasamy, V., Kuan, L. Y., Morales, M. A. Lopez, Pires, T., and Azevedo, L. C. P.

Subjects
Meeting Abstracts
Abstract

Introduction In addition to systemic hemodynamics, the management\ud of neurocritically ill patients is often informed by neuromonitoring. In\ud the absence of high-level evidence clinicians are often guided by personal\ud and local expertise. Little is known about practices as they pertain\ud to the use of such monitoring in patients with acute brain injury (ABI).\ud Objectives To investigate practices in bedside monitoring for ABI patients.\ud Particularly interested in differences among “neurointensivists”\ud (NIs; defined here as intensivists whose clinical practice is comprised\ud > 1/3 by neurocritical care) and other intensivists (OIs). Also, to\ud explore patterns specific to traumatic brain injury (TBI) and subarachnoid\ud hemorrhage (SAH), as well as preferences and availability of\ud particular technologies/devices.\ud Methods Electronic survey of 22 items including two case-based scenarios;\ud endorsed by SCCM (9,000 recipients) and ESICM (on-line\ud newsletter) in 2013. A sample size of 370 was calculated based on a\ud population of 10,000 physician members, a 5 % margin error, and\ud 95 % confidence interval. We summarized results using descriptive\ud statistics (proportions with 95 % confidence intervals). A chi-square\ud test was used to compare proportions of responses between NIs and\ud OIs with a significance p < 0.05.\ud Results There were 655 responders (66 % completion rate); 422(65 %)\ud were classified as OIs and 226(35 %) as NIs. More NIs follow\ud hemodynamic protocols for neurocritically-ill patients (56 % vs. 43 %, p\ud 0.001), in TBI (44.5 % vs. 33.3 %, p 0.007), and in SAH (38.1 % vs. 21.3 %,\ud p < 000.1). For delayed cerebral ischemia (DCI), more NIs target cardiac\ud index (CI) (35 % vs. 21 %, p 0.0001), and fluid responsiveness (62 % vs.\ud 53 %, p 0.03), use more bedside ultrasound (BUS) (42 % vs. 29 %, p\ud 0.005) and arterial waveform analysis (40 % vs. 29 %, p 0.02). For DCI\ud neuromonitoring, NIs use more angiography (57 % vs. 43 %, p 0.004),\ud TCD (46 % vs. 38 %, p 0.0001), and CTP (32 % vs.16 %, p 0.0001). For\ud CPP optimization in TBI, NIs use more arterial waveform analysis (45 %\ud vs. 35 %, p 0.019), and BUS (37 % vs. 27.7 %, p 0.023), while more OIs\ud monitor mixed venous oxygen saturation (54.1 % vs. 45 %, p 0.045). For\ud TBI neuromonitoring, NIs use more PbtO2 (28 % vs. 10 %, p 0.0001). In\ud the case scenario of raised ICP/low PbtO2, most employ analgosedation\ud (47 %) and osmotherapy (38 %). Fewer make use of preserved pressure\ud reactivity, particularly OIs (vasopressor use 23 % vs. 34 %, p 0.014).\ud Conclusions There is large heterogeneity in the use of monitoring protocols,\ud variables, and technologies/devices. “Neurointensivists” not only\ud employ more neuromonitoring but also more hemodynamic monitoring\ud in patients with acute brain injury. ICP/CPP remain the most commonly\ud followed neuro-variables in TBI patients, with low use of other\ud brain-physiology parameters, sugg

Published
2016

15. A consensus molecular subtypes classification strategy for clinical colorectal cancer tissues.

Author

de Back TR, Wu T, Schafrat PJ, Ten Hoorn S, Tan M, He L, van Hooff SR, Koster J, Nijman LE, Vink GR, Beumer IJ, Elbers CC, Lenos KJ, Sommeijer DW, Wang X, and Vermeulen L

Subjects
Humans, Paraffin Embedding, Biomarkers, Tumor genetics, ErbB Receptors genetics, ErbB Receptors metabolism, Female, Consensus, Tissue Fixation methods, Male, Gene Expression Profiling methods, Aged, Middle Aged, Prognosis, Gene Expression Regulation, Neoplastic, Formaldehyde, Colorectal Neoplasms genetics, Colorectal Neoplasms classification, Colorectal Neoplasms pathology
Abstract

Consensus Molecular Subtype (CMS) classification of colorectal cancer (CRC) tissues is complicated by RNA degradation upon formalin-fixed paraffin-embedded (FFPE) preservation. Here, we present an FFPE-curated CMS classifier. The CMSFFPE classifier was developed using genes with a high transcript integrity in FFPE-derived RNA. We evaluated the classification accuracy in two FFPE-RNA datasets with matched fresh-frozen (FF) RNA data, and an FF-derived RNA set. An FFPE-RNA application cohort of metastatic CRC patients was established, partly treated with anti-EGFR therapy. Key characteristics per CMS were assessed. Cross-referenced with matched benchmark FF CMS calls, the CMSFFPE classifier strongly improved classification accuracy in two FFPE datasets compared with the original CMSClassifier (63.6% versus 40.9% and 83.3% versus 66.7%, respectively). We recovered CMS-specific recurrence-free survival patterns (CMS4 versus CMS2: hazard ratio 1.75, 95% CI 1.24-2.46). Key molecular and clinical associations of the CMSs were confirmed. In particular, we demonstrated the predictive value of CMS2 and CMS3 for anti-EGFR therapy response (CMS2&3: odds ratio 5.48, 95% CI 1.10-27.27). The CMSFFPE classifier is an optimized FFPE-curated research tool for CMS classification of clinical CRC samples., (© 2024 de Back et al.)

Published
2024
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16. Total neoadjuvant therapy with or without aflibercept in rectal cancer: 3-year results of GEMCAD-1402.

Author

Pesántez D, Ten Hoorn S, Machado I, García-Albéniz X, Rodríguez-Salas N, Heredia-Soto V, Viñal D, Pericay C, García-Carbonero R, Losa F, Alonso V, Vera R, Feliu Batlle J, Gallego J, Salud A, Nogué M, Layos L, Montagut C, Capdevila J, Vermeulen L, Maurel J, and Fernandez-Martos C

Subjects
Humans, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Neoplasm Recurrence, Local epidemiology, Neoplasm Recurrence, Local pathology, Fluorouracil therapeutic use, Capecitabine therapeutic use, Chemoradiotherapy methods, Recurrence, Neoplasm Staging, Neoadjuvant Therapy, Rectal Neoplasms drug therapy, Rectal Neoplasms pathology
Abstract

Background: The results of the Grupo Español Multidisciplinar en Cáncer Digestivo (GEMCAD)-1402 phase II randomized trial suggested that adding aflibercept to modified fluorouracil, oxaliplatin, and leucovorin (mFOLFOX6) induction, followed by chemoradiation and surgery, could increase the pathological complete response (pCR) rate in patients with high-risk, locally advanced rectal cancer. Here we update results up to 3 years of follow-up and evaluate the predictive value of consensus molecular subtypes identified with immunohistochemistry (IHC)., Methods: Patients with magnetic resonance imaging-defined T3c-d and/or T4 and/or N2 rectal adenocarcinoma in the middle or distal third were randomly assigned to mFOLFOX6 induction, with aflibercept (mF+A; n = 115) or without aflibercept (mF; n = 65), followed by capecitabine plus radiotherapy and surgery. The risk local relapse, distant metastases, disease-free survival (DFS), and overall survival (OS) were estimated at 3 years. Selected samples were classified via IHC into immune-infiltrate, epithelial, or mesenchymal subtypes., Results: mF+A and mF had 3-year DFS of 75.2% (95% confidence interval [CI] = 66.1% to 82.2%) and 81.5% (95% CI = 69.8% to 89.1%), respectively; 3-year OS of 89.3% (95% CI = 82.0% to 93.8%) and 90.7% (95% CI = 80.6% to 95.7%), respectively; 3-year cumulative local relapse incidences of 5.2% (95% CI = 1.9% to 11.0%) and 6.1% (95% CI = 1.7% to 15.0%), respectively; and 3-year cumulative distant metastases rates of 17.3% (95% CI = 10.9% to 25.5%) and 16.9% (95% CI = 8.7% to 28.2%), respectively. pCRs were achieved in 27.5% (n = 22 of 80) and 0% (n = 0 of 10) of patients with epithelial and mesenchymal subtypes, respectively., Conclusion: Adding aflibercept to mFOLFOX6 induction was not associated with improved DFS or OS. Our findings suggested that consensus molecular subtypes identified with IHC subtypes could be predictive of pCR with this treatment., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Published
2023
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17. Long-term Survival Update and Extended RAS Mutational Analysis of the CAIRO2 Trial: Addition of Cetuximab to CAPOX/Bevacizumab in Metastatic Colorectal Cancer.

Author

Ten Hoorn S, Mol L, Sommeijer DW, Nijman L, van den Bosch T, de Back TR, Ylstra B, van Dijk E, van Noesel CJM, Reinten RJ, Nagtegaal ID, Koopman M, Punt CJA, and Vermeulen L

Subjects
Humans, Cetuximab, Bevacizumab, Capecitabine, Oxaliplatin therapeutic use, Proto-Oncogene Proteins B-raf genetics, Retrospective Studies, Disease-Free Survival, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Mutation, Proto-Oncogene Proteins p21(ras) genetics, Colorectal Neoplasms drug therapy, Colorectal Neoplasms genetics, Colorectal Neoplasms pathology, Colonic Neoplasms drug therapy, Rectal Neoplasms drug therapy
Abstract

Background: Here we present updated survival of the CAIRO2 trial and assessed whether the addition of anti-EGFR to anti-VEGF therapy could still be an effective treatment option for patients with extended RAS/BRAF wildtype and left-sided metastatic colorectal cancer (mCRC)., Materials and Methods: Retrospective updated survival and extended RAS and BRAF V600E mutational analysis were performed in the CAIRO2 trial, a multicenter, randomized phase III trial on the effect of adding cetuximab to a combination of capecitabine, oxaliplatin (CAPOX), and bevacizumab in mCRC., Results: Updated survival analysis confirmed that the addition of cetuximab did not provide a benefit on either progression free (PFS) or overall survival (OS) in the intention-to-treat population. With the extended mutational analyses 31 KRAS, 31 NRAS and 12 BRAF V600E additional mutations were found. No benefit of the addition of cetuximab was observed within the extended wildtype group, even when selecting only left-sided tumors (PFS HR 0.96, p = 0.7775). However, compared to the original trial an increase of 6.5 months was seen for patients with both extended wildtype and left-sided tumors (median OS 28.6 months)., Conclusion: Adding cetuximab to CAPOX and bevacizumab does not provide clinical benefit in patients with mCRC, even in the extended wildtype group with left-sided tumors. However, in the extended wildtype group we did observe clinically relevant higher survival compared to the initial trial report, indicating that it is important to analyze a broader panel of RAS and BRAF variants using more recent sequencing techniques when assessing survival benefit after anti-EGFR therapy., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Published
2023
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18. Molecular characterization of colorectal cancer related peritoneal metastatic disease.

Author

Lenos KJ, Bach S, Ferreira Moreno L, Ten Hoorn S, Sluiter NR, Bootsma S, Vieira Braga FA, Nijman LE, van den Bosch T, Miedema DM, van Dijk E, Ylstra B, Kulicke R, Davis FP, Stransky N, Smolen GA, Coebergh van den Braak RRJ, IJzermans JNM, Martens JWM, Hallam S, Beggs AD, Kops GJPL, Lansu N, Bastiaenen VP, Klaver CEL, Lecca MC, El Makrini K, Elbers CC, Dings MPG, van Noesel CJM, Kranenburg O, Medema JP, Koster J, Koens L, Punt CJA, Tanis PJ, de Hingh IH, Bijlsma MF, Tuynman JB, and Vermeulen L

Subjects
Humans, Peritoneum metabolism, Quality of Life, Colorectal Neoplasms pathology, Neoplasms, Second Primary, Peritoneal Neoplasms genetics, Peritoneal Neoplasms secondary
Abstract

A significant proportion of colorectal cancer (CRC) patients develop peritoneal metastases (PM) in the course of their disease. PMs are associated with a poor quality of life, significant morbidity and dismal disease outcome. To improve care for this patient group, a better understanding of the molecular characteristics of CRC-PM is required. Here we present a comprehensive molecular characterization of a cohort of 52 patients. This reveals that CRC-PM represent a distinct CRC molecular subtype, CMS4, but can be further divided in three separate categories, each presenting with unique features. We uncover that the CMS4-associated structural protein Moesin plays a key role in peritoneal dissemination. Finally, we define specific evolutionary features of CRC-PM which indicate that polyclonal metastatic seeding underlies these lesions. Together our results suggest that CRC-PM should be perceived as a distinct disease entity., (© 2022. The Author(s).)

Published
2022
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19. Development of a miRNA-based classifier for detection of colorectal cancer molecular subtypes.

Author

Adam RS, Poel D, Ferreira Moreno L, Spronck JMA, de Back TR, Torang A, Gomez Barila PM, Ten Hoorn S, Markowetz F, Wang X, Verheul HMW, Buffart TE, and Vermeulen L

Subjects
Biomarkers, Tumor genetics, Gene Expression Profiling, Humans, Microsatellite Instability, RNA, Messenger genetics, Transcriptome, Colorectal Neoplasms diagnosis, Colorectal Neoplasms genetics, Colorectal Neoplasms pathology, MicroRNAs genetics
Abstract

Previously, colorectal cancer (CRC) has been classified into four distinct molecular subtypes based on transcriptome data. These consensus molecular subtypes (CMSs) have implications for our understanding of tumor heterogeneity and the prognosis of patients. So far, this classification has been based on the use of messenger RNAs (mRNAs), although microRNAs (miRNAs) have also been shown to play a role in tumor heterogeneity and biological differences between CMSs. In contrast to mRNAs, miRNAs have a smaller size and increased stability, facilitating their detection. Therefore, we built a miRNA-based CMS classifier by converting the existing mRNA-based CMS classification using machine learning (training dataset of n = 271). The performance of this miRNA-assigned CMS classifier (CMS-miRaCl) was evaluated in several datasets, achieving an overall accuracy of ~ 0.72 (0.6329-0.7987) in the largest dataset (n = 158). To gain insight into the biological relevance of CMS-miRaCl, we evaluated the most important features in the classifier. We found that miRNAs previously reported to be relevant in microsatellite-instable CRCs or Wnt signaling were important features for CMS-miRaCl. Following further studies to validate its robustness, this miRNA-based alternative might simplify the implementation of CMS classification in clinical workflows., (© 2022 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Published
2022
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20. Serum-based measurements of stromal activation through ADAM12 associate with poor prognosis in colorectal cancer.

Author

Ten Hoorn S, Waasdorp C, van Oijen MGH, Damhofer H, Trinh A, Zhao L, Smits LJH, Bootsma S, van Pelt GW, Mesker WE, Mol L, Goey KKH, Koopman M, Medema JP, Tuynman JB, Zlobec I, Punt CJA, Vermeulen L, and Bijlsma MF

Subjects
ADAM12 Protein genetics, ADAM12 Protein metabolism, Biomarkers, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, Humans, Prognosis, Retrospective Studies, Cancer-Associated Fibroblasts metabolism, Colonic Neoplasms, Colorectal Neoplasms pathology, Rectal Neoplasms
Abstract

Background: Recently it has been recognized that stromal markers could be used as a clinically relevant biomarker for therapy response and prognosis. Here, we report on a serum marker for stromal activation, A Disintegrin and Metalloprotease 12 (ADAM12) in colorectal cancer (CRC)., Methods: Using gene expression databases we investigated ADAM12 expression in CRC and delineated the source of ADAM12 expression. The clinical value of ADAM12 was retrospectively assessed in the CAIRO2 trial in metastatic CRC with 235 patients (31% of total cohort), and an independent rectal cancer cohort (n = 20)., Results: ADAM12 is expressed by activated CRC associated fibroblasts. In the CAIRO2 trial cohort, ADAM12 serum levels were prognostic (ADAM12 low versus ADAM12 high; median OS 25.3 vs. 17.1 months, HR 1.48 [95% CI 1.11-1.96], P = 0.007). The prognostic potential was specifically high for metastatic rectal cancer (HR 1.78 [95% CI 1.06-3.00], P = 0.030) and mesenchymal subtype tumors (HR 2.12 [95% CI 1.25-3.60], P = 0.004). ADAM12 also showed potential for predicting recurrence in an exploratory analysis of non-metastatic rectal cancers., Conclusions: Here we describe a non-invasive marker for activated stroma in CRC which associates with poor outcome, especially for primary cancers located in the rectum., (© 2022. The Author(s).)

Published
2022
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21. Clinical Value of Consensus Molecular Subtypes in Colorectal Cancer: A Systematic Review and Meta-Analysis.

Author

Ten Hoorn S, de Back TR, Sommeijer DW, and Vermeulen L

Subjects
Bevacizumab therapeutic use, Biomarkers, Tumor genetics, Humans, Oxaliplatin therapeutic use, Prognosis, Colorectal Neoplasms drug therapy, Colorectal Neoplasms genetics, Gene Expression Profiling
Abstract

Background: The consensus molecular subtypes (CMSs) of colorectal cancer (CRC) capture tumor heterogeneity at the gene-expression level. Currently, a restricted number of molecular features are used to guide treatment for CRC. We summarize the evidence on the clinical value of the CMSs., Methods: We systematically identified studies in Medline and Embase that evaluated the prognostic and predictive value of CMSs in CRC patients. A random-effect meta-analysis was performed on prognostic data. Predictive data were summarized., Results: In local disease, CMS4 tumors were associated with worse overall survival (OS) compared with CMS1 (hazard ratio [HR] = 3.28, 95% confidence interval = 1.27 to 8.47) and CMS2 cancers (HR = 2.60, 95% confidence interval = 1.93 to 3.50). In metastatic disease, CMS1 consistently had worse survival than CMS2-4 (OS HR range = 0.33-0.55; progression-free survival HR range = 0.53-0.89). Adjuvant chemotherapy in stage II and III CRC was most beneficial for OS in CMS2 and CMS3 (HR range = 0.16-0.45) and not effective in CMS4 tumors. In metastatic CMS4 cancers, an irinotecan-based regimen improved outcome compared with oxaliplatin (HR range = 0.31-0.72). The addition of bevacizumab seemed beneficial in CMS1, and anti-epidermal growth factor receptor therapy improved outcome for KRAS wild-type CMS2 patients., Conclusions: The CMS classification holds clear potential for clinical use in predicting both prognosis and response to systemic therapy, which seems to be independent of the classifier used. Prospective studies are warranted to support implementation of the CMS taxonomy in clinical practice., (© The Author(s) 2021. Published by Oxford University Press.)

Published
2022
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22. Molecular subtype-specific efficacy of anti-EGFR therapy in colorectal cancer is dependent on the chemotherapy backbone.

Author

Ten Hoorn S, Sommeijer DW, Elliott F, Fisher D, de Back TR, Trinh A, Koens L, Maughan T, Seligmann J, Seymour MT, Quirke P, Adams R, Richman SD, Punt CJA, and Vermeulen L

Subjects
Aged, Antineoplastic Combined Chemotherapy Protocols pharmacology, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cetuximab pharmacology, Cetuximab therapeutic use, Clinical Trials as Topic, Colorectal Neoplasms classification, Colorectal Neoplasms genetics, ErbB Receptors antagonists & inhibitors, Female, Humans, Irinotecan pharmacology, Male, Middle Aged, Neoplasm Metastasis, Oxaliplatin pharmacology, Panitumumab pharmacology, Panitumumab therapeutic use, Protein Kinase Inhibitors pharmacology, Proto-Oncogene Proteins B-raf genetics, Retrospective Studies, Survival Analysis, Treatment Outcome, ras Proteins genetics, Colorectal Neoplasms drug therapy, Irinotecan therapeutic use, Oxaliplatin therapeutic use, Protein Kinase Inhibitors therapeutic use
Abstract

Background: Patient selection for addition of anti-EGFR therapy to chemotherapy for patients with RAS and BRAF wildtype metastatic colorectal cancer can still be optimised. Here we investigate the effect of anti-EGFR therapy on survival in different consensus molecular subtypes (CMSs) and stratified by primary tumour location., Methods: Retrospective analyses, using the immunohistochemistry-based CMS classifier, were performed in the COIN (first-line oxaliplatin backbone with or without cetuximab) and PICCOLO trial (second-line irinotecan with or without panitumumab). Tumour tissue was available for 323 patients (20%) and 349 (41%), respectively., Results: When using an irinotecan backbone, anti-EGFR therapy is effective in both CMS2/3 and CMS4 in left-sided primary tumours (progression-free survival (PFS): HR 0.44, 95% CI 0.26-0.75, P = 0.003 and HR 0.12, 95% CI 0.04-0.36, P < 0.001, respectively) and in CMS4 right-sided tumours (PFS HR 0.17, 95% CI 0.04-0.71, P = 0.02). Efficacy using an oxaliplatin backbone was restricted to left-sided CMS2/3 tumours (HR 0.57, 95% CI 0.36-0.96, P = 0.034)., Conclusions: The subtype-specific efficacy of anti-EGFR therapy is dependent on the chemotherapy backbone. This may provide the possibility of subtype-specific treatment strategies for a more optimal use of anti-EGFR therapy., (© 2021. The Author(s).)

Published
2021
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23. The recurring features of molecular subtypes in distinct gastrointestinal malignancies-A systematic review.

Author

Adam RS, Blomberg I, Ten Hoorn S, Bijlsma MF, and Vermeulen L

Subjects
Gene Expression Regulation, Neoplastic, Humans, Neoplasm Recurrence, Local, Carcinoma, Pancreatic Ductal genetics, Gastrointestinal Neoplasms diagnosis, Gastrointestinal Neoplasms genetics, Pancreatic Neoplasms diagnosis, Pancreatic Neoplasms genetics
Abstract

In colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC) and gastric cancer (GC) multiple studies of inter-tumor heterogeneity have identified molecular subtypes, which correlate with clinical features. Our aim was to investigate the attributes of molecular subtypes across three different gastrointestinal cancer types. We performed a systematic search for publications on molecular subtypes or classifications in PDAC and GC and compared the described subtypes with the established consensus molecular subtypes of CRC. Examining the characteristics of subtypes across CRC, PDAC and GC resulted in four categories of subtypes. We describe uniting and distinguishing features within a mesenchymal, an epithelial, an immunogenic and a metabolic and digestive subtype category. We conclude that molecular subtypes of CRC, PDAC and GC display relevant overlap in molecular features and clinical outcomes. This finding encourages quantitative studies on subtypes across different cancer types and could lead to a paradigm shift in future treatment strategies., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Published
2021
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24. Apc-mutant cells act as supercompetitors in intestinal tumour initiation.

Author

van Neerven SM, de Groot NE, Nijman LE, Scicluna BP, van Driel MS, Lecca MC, Warmerdam DO, Kakkar V, Moreno LF, Vieira Braga FA, Sanches DR, Ramesh P, Ten Hoorn S, Aelvoet AS, van Boxel MF, Koens L, Krawczyk PM, Koster J, Dekker E, Medema JP, Winton DJ, Bijlsma MF, Morrissey E, Léveillé N, and Vermeulen L

Subjects
Adenoma genetics, Adenoma metabolism, Adenoma pathology, Adenomatous Polyposis Coli Protein deficiency, Animals, Cell Differentiation genetics, Female, Glycogen Synthase Kinase 3 beta antagonists & inhibitors, Humans, Intestinal Neoplasms metabolism, Lithium Chloride pharmacology, Male, Mice, Organoids cytology, Organoids metabolism, Organoids pathology, Wnt Proteins antagonists & inhibitors, Wnt Proteins metabolism, Adenomatous Polyposis Coli Protein genetics, Cell Competition, Genes, APC, Intestinal Neoplasms genetics, Intestinal Neoplasms pathology, Mutation
Abstract

A delicate equilibrium of WNT agonists and antagonists in the intestinal stem cell (ISC) niche is critical to maintaining the ISC compartment, as it accommodates the rapid renewal of the gut lining. Disruption of this balance by mutations in the tumour suppressor gene APC, which are found in approximately 80% of all human colon cancers, leads to unrestrained activation of the WNT pathway 1,2 . It has previously been established that Apc-mutant cells have a competitive advantage over wild-type ISCs 3 . Consequently, Apc-mutant ISCs frequently outcompete all wild-type stem cells within a crypt, thereby reaching clonal fixation in the tissue and initiating cancer formation. However, whether the increased relative fitness of Apc-mutant ISCs involves only cell-intrinsic features or whether Apc mutants are actively involved in the elimination of their wild-type neighbours remains unresolved. Here we show that Apc-mutant ISCs function as bona fide supercompetitors by secreting WNT antagonists, thereby inducing differentiation of neighbouring wild-type ISCs. Lithium chloride prevented the expansion of Apc-mutant clones and the formation of adenomas by rendering wild-type ISCs insensitive to WNT antagonists through downstream activation of WNT by inhibition of GSK3β. Our work suggests that boosting the fitness of healthy cells to limit the expansion of pre-malignant clones may be a powerful strategy to limit the formation of cancers in high-risk individuals.

Published
2021
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25. Tumour budding is associated with the mesenchymal colon cancer subtype and RAS/RAF mutations: a study of 1320 colorectal cancers with Consensus Molecular Subgroup (CMS) data.

Author

Trinh A, Lädrach C, Dawson HE, Ten Hoorn S, Kuppen PJK, Reimers MS, Koopman M, Punt CJA, Lugli A, Vermeulen L, and Zlobec I

Subjects
Adult, Aged, Aged, 80 and over, Biomarkers, Tumor metabolism, Cohort Studies, Colorectal Neoplasms classification, Colorectal Neoplasms metabolism, Epithelial-Mesenchymal Transition, Female, Humans, Male, Mesoderm pathology, Middle Aged, Prognosis, Randomized Controlled Trials as Topic, Colorectal Neoplasms pathology, Genes, ras, Mutation, raf Kinases genetics
Abstract

Background: Tumour budding is an important prognostic factor in colorectal cancer (CRC). Molecular profiling of tumour buds suggests (partial) epithelial-mesenchymal transition and cancer stem-cell phenotype, similarly described in the "mesenchymal" Consensus Molecular Subtype 4 (CMS4), which identifies a particularly poor prognostic subgroup. Here, we determine the association of tumour budding with CMS classification, prognosis, and response to therapy., Methods: AMC-AJCCII-90 cohort (n = 76, stage II) was evaluated for peritumoural budding on H&E slides. LUMC (n = 270, stage I-IV), CAIRO (n = 504, metastatic CRC) and CAIRO2 (n = 472, metastatic CRC) cohorts were investigated for intratumoural budding using pan-cytokeratin-stained tissue microarrays. Budding was scored as count/area, then classified as <5 or ≥5 buds. For all cohorts, CMS classifications were available (gene-expression/immunohistochemistry-based classifiers)., Results: High (≥5) budding predicted a worse outcome in multivariate analysis in AMC-AJCCII-90 (p = 0.018), LUMC (p < 0.0001), and CAIRO (p = 0.03), and in CAIRO2 (continuous variable, p = 0.02). Tumour budding counts were higher in CMS4 compared to epithelial CMS2/3 cancers (p < 0.01, all), and associated with KRAS/BRAF mutations (p < 0.01, AMC-AJCCII-90, CAIRO, CAIRO2)., Conclusion: Tumour budding is an adverse prognostic factor across all CRC stages and is associated with the mesenchymal CMS4 phenotype. KRAS/BRAF mutations are strongly correlated with tumour budding suggesting their involvement in the regulation of this process.

Published
2018
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26. Classification of Colorectal Cancer in Molecular Subtypes by Immunohistochemistry.

Author

Ten Hoorn S, Trinh A, de Jong J, Koens L, and Vermeulen L

Subjects
CDX2 Transcription Factor analysis, Colorectal Neoplasms genetics, Cytoskeletal Proteins analysis, Humans, Immunohistochemistry instrumentation, Internet, Membrane Proteins analysis, Microscopy instrumentation, Microscopy methods, Receptor, Serotonin, 5-HT2B analysis, Zinc Finger E-box-Binding Homeobox 1 analysis, Biomarkers, Tumor analysis, Colorectal Neoplasms pathology, Image Processing, Computer-Assisted methods, Immunohistochemistry methods, Microsatellite Instability
Abstract

Colorectal cancer (CRC) is a heterogeneous disease, which can be categorized into distinct consensus molecular subtypes (CMSs). These subtypes differ in both clinical as well as biological properties. The gold-standard classification strategy relies on genome-wide expression data, which hampers widespread implementation. Here we describe an immunohistochemical (IHC) Mini Classifier, a practical tool that, in combination with microsatellite instability testing, delivers objective and accurate scoring to classify CRC patients into the main molecular disease subtypes. It is a robust immunohistochemical-based assay containing four specific stainings (FRMD6, ZEB1, HTR2B, and CDX2) in combination with cytokeratin. We also describe an online tool for classification of individual samples based on scoring parameters of these stainings.

Published
2018
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