Search

Your search keyword '"Vlachogiannis G"' showing total 45 results
Start Over Author "Vlachogiannis G"
45 results on '"Vlachogiannis G"'

1. Investigation of unique dependencies of cells lacking the PTEN tumour suppressor gene

Author

Vlachogiannis, G. and Downward, J.

Subjects
616.99
Abstract

Over the past ten years significant effort has been put in the identification of pharmacological targets that facilitate the selective targeting of cancer cells. The concept of synthetic lethality in combination with RNA interference (RNAi) technology provides an attractive platform for the identification of such drug targets. With this in mind I designed, set up, and executed a large-scale siRNA screen aiming at identifying genes that exhibit a synthetic lethal relationship with loss of the PI3K/AKT signalling cascade negative regulator PTEN. A PTEN-isogenic cell system derived from the breast epithelial cell line MCF10A was employed in this study, and screened with a siRNA library against the “Druggable genome”. Putative hits exhibiting a potential synthetic lethal relationship with loss of PTEN were identified by differential Z-score analysis, and validated in a panel of breast cancer cell lines segregated based on their PTEN status. This analysis identified several PTEN-loss synthetic lethal candidate genes whose further evaluation may reveal new insights in the biology of PTEN null cancer cells. The functional mechanism underlying one of the identified PTEN-loss synthetic lethal putative hits (CYTH1/PSCD1) was investigated in detail. Knockdown of CYTH1 selectively induced apoptosis in the PTEN-/- MCF10A cells, and biochemical and genetic evidence supported a potential synthetic lethal relationship with PI3K/AKT pathway activation due to loss of PTEN. Although definite confirmation that CYTH1 was the sole target mediating the identified PTEN-loss synthetic lethal interaction was not obtained, further investigation on the exact nature of the described PTEN-loss synthetic lethal relationship may have the potential to uncover previously unknown vulnerabilities of PTEN-deficient cancer cells that could be pharmacologically exploited.

Published
2013

2. Validation of the new Sepsis-3 definitions: proposal for improvement in early risk identification

Author

Giamarellos-Bourboulis, E.J., Tsaganos, T., Tsangaris, I., Lada, M., Routsi, C., Sinapidis, D., Koupetori, M., Bristianou, M., Adamis, G., Mandragos, K., Dalekos, G.N., Kritselis, I., Giannikopoulos, G., Koutelidakis, I., Pavlaki, M., Antoniadou, E., Vlachogiannis, G., Koulouras, V., Prekates, A., Dimopoulos, G., Koutsoukou, A., Pnevmatikos, I., Ioakeimidou, A., Kotanidou, A., Orfanos, S.E., Armaganidis, A., and Gogos, C.

Published
2017
Full Text
View/download PDF

5. EGFR amplification (amp) and survival in the REAL-3 trial

Author

Smyth, E., primary, Kouvelakis, K., additional, Cunningham, D., additional, Hahne, J.C., additional, Peckitt, C., additional, Vlachogiannis, G., additional, Watkins, D., additional, Rao, S., additional, Starling, N., additional, Wilson, S.H., additional, Waddell, T.S., additional, Okines, A., additional, Crosby, T., additional, Mansoor, W., additional, Wadsley, J., additional, Middleton, G., additional, Wotherspoon, A., additional, Chau, I., additional, and Valeri, N., additional

Published
2018
Full Text
View/download PDF

8. Validation of the new Sepsis-3 definitions: proposal for improvement in early risk identification

Author

Giamarellos-Bourboulis, E.J. Tsaganos, T. Tsangaris, I. Lada, M. Routsi, C. Sinapidis, D. Koupetori, M. Bristianou, M. Adamis, G. Mandragos, K. Dalekos, G.N. Kritselis, I. Giannikopoulos, G. Koutelidakis, I. Pavlaki, M. Antoniadou, E. Vlachogiannis, G. Koulouras, V. Prekates, A. Dimopoulos, G. Koutsoukou, A. Pnevmatikos, I. Ioakeimidou, A. Kotanidou, A. Orfanos, S.E. Armaganidis, A. Gogos, C. the Hellenic Sepsis Study Group

Subjects
health care facilities, manpower, and services
Abstract

Objectives Sepsis-3 definitions generated controversies regarding their general applicability. The Sepsis-3 Task Force outlined the need for validation with emphasis on the quick Sequential Organ Failure Assessment (qSOFA) score. This was done in a prospective cohort from a different healthcare setting. Methods Patients with infections and at least two signs of systemic inflammatory response syndrome (SIRS) were analysed. Sepsis was defined as total SOFA ≥2 outside the intensive care unit (ICU) or as an increase of ICU admission SOFA ≥2. The primary endpoints were the sensitivity of qSOFA outside the ICU and sepsis definition both outside and within the ICU to predict mortality. Results In all, 3346 infections outside the ICU and 1058 infections in the ICU were analysed. Outside the ICU, respective mortality with ≥2 SIRS and qSOFA ≥2 was 25.3% and 41.2% (p

Published
2017

9. 36th International Symposium on Intensive Care and Emergency Medicine

Author

Bateman, R. M., Sharpe, M. D., Jagger, J. E., Ellis, C. G., Solé-Violán, J., López-Rodríguez, M., Herrera-Ramos, E., Ruíz-Hernández, J., Borderías, L., Horcajada, J., González-Quevedo, N., Rajas, O., Briones, M., Rodríguez de Castro, F., Rodríguez Gallego, C., Esen, F., Orhun, G., Ergin Ozcan, P., Senturk, E., Ugur Yilmaz, C., Orhan, N., Arican, N., Kaya, M., Kucukerden, M., Giris, M., Akcan, U., Bilgic Gazioglu, S., Tuzun, E., Riff, R., Naamani, O., Douvdevani, A., Takegawa, R., Yoshida, H., Hirose, T., Yamamoto, N., Hagiya, H., Ojima, M., Akeda, Y., Tasaki, O., Tomono, K., Shimazu, T., Ono, S., Kubo, T., Suda, S., Ueno, T., Ikeda, T., Ogura, H., Takahashi, H., Kang, J., Nakamura, Y., Kojima, T., Izutani, Y., Taniguchi, T., O, M., Dinter, C., Lotz, J., Eilers, B., Wissmann, C., Lott, R., Meili, M. M., Schuetz, P. S., Hawa, H., Sharshir, M., Aburageila, M., Salahuddin, N., Chantziara, V., Georgiou, S., Tsimogianni, A., Alexandropoulos, P., Vassi, A., Lagiou, F., Valta, M., Micha, G., Chinou, E., Michaloudis, G., Kodaira, A., Imaizumi, H., De la Torre-Prados, M. V., Garcia-De la Torre, A., Enguix-Armada, A., Puerto-Morlan, A., Perez-Valero, V., Garcia-Alcantara, A., Bolton, N., Dudziak, J., Bonney, S., Tridente, A., Nee, P., Nicolaes, G., Wiewel, M., Schultz, M., Wildhagen, K., Horn, J., Schrijver, R., Van der Poll, T., Reutelingsperger, C., Pillai, S., Davies, G., Mills, G., Aubrey, R., Morris, K., Williams, P., Evans, P., Gayat, E. G., Struck, J., Cariou, A., Deye, N., Guidet, B., Jabert, S., Launay, J., Legrand, M., Léone, M., Resche-Rigon, M., Vicaut, E., Vieillard-Baron, A., Mebazaa, A., Arnold, R., Capan, M., Linder, A., Akesson, P., Popescu, M., Tomescu, D., Sprung, C. L., Calderon Morales, R., Munteanu, G., Orenbuch-Harroch, E., Levin, P., Kasdan, H., Reiter, A., Volker, T., Himmel, Y., Cohen, Y., Meissonnier, J., Girard, L., Rebeaud, F., Herrmann, I., Delwarde, B., Peronnet, E., Cerrato, E., Venet, F., Lepape, A., Rimmelé, T., Monneret, G., Textoris, J., Beloborodova, N., Moroz, V., Osipov, A., Bedova, A., Sarshor, Y., Pautova, A., Sergeev, A., Chernevskaya, E., Odermatt, J., Bolliger, R., Hersberger, L., Ottiger, M., Christ-Crain, M., Mueller, B., Schuetz, P., Sharma, N. K., Tashima, A. K., Brunialti, M. K., Machado, F. R., Assuncao, M., Rigato, O., Salomao, R., Cajander, S. C., Rasmussen, G., Tina, E., Söderquist, B., Källman, J., Strålin, K., Lange, A. L., Sundén-Cullberg, J. S., Magnuson, A. M., Hultgren, O. H., Van der Geest, P., Mohseni, M., Linssen, J., De Jonge, R., Duran, S., Groeneveld, J., Miller, R., Lopansri, B. K., McHugh, L. C., Seldon, A., Burke, J. P., Johnston, J., Reece-Anthony, R., Bond, A., Molokhia, A., Mcgrath, C., Nsutebu, E., Bank Pedersen, P., Pilsgaard Henriksen, D., Mikkelsen, S., Touborg Lassen, A., Tincu, R., Cobilinschi, C., Ghiorghiu, Z., Macovei, R., Wiewel, M. A., Harmon, M. B., Van Vught, L. A., Scicluna, B. P., Hoogendijk, A. J., Zwinderman, A. H., Cremer, O. L., Bonten, M. J., Schultz, M. J., Juffermans, N. P., Wiersinga, W. J., Eren, G., Tekdos, Y., Dogan, M., Acicbe, O., Kaya, E., Hergunsel, O., Alsolamy, S., Ghamdi, G., Alswaidan, L., Alharbi, S., Alenezi, F., Arabi, Y., Heaton, J., Boyce, A., Nolan, L., Dukoff-Gordon, A., Dean, A., Mann Ben Yehudah, T., Fleischmann, C., Thomas-Rueddel, D., Haas, C., Dennler, U., Reinhart, K., Suntornlohanakul, O., Khwannimit, B., Breckenridge, F., Puxty, A., Szturz, P., Folwarzcny, P., Svancara, J., Kula, R., Sevcik, P., Caneva, L., Casazza, A., Bellazzi, E., Marra, S., Pagani, L., Vetere, M., Vanzino, R., Ciprandi, D., Preda, R., Boschi, R., Carnevale, L., Lopez, V., Aguilar Arzapalo, M., Barradas, L., Escalante, A., Gongora, J., Cetina, M., Adamik, B, Jakubczyk, D, Kübler, A, Radford, A., Lee, T., Singer, J., Boyd, J., Fineberg, D., Williams, M., Russell, J., Scarlatescu, E., Droc, G., Arama, S., Müller, M., Straat, M., Zeerleder, S. S., Fuchs, C. F., Scheer, C. S., Wauschkuhn, S. W., Vollmer, M. V., Meissner, K. M., Kuhn, S. K., Hahnenkamp, K. H., Rehberg, S. R., Gründling, M. G., Hamaguchi, S., Gómez-Sánchez, E., Heredia-Rodríguez, M., Álvarez-Fuente, E., Lorenzo-López, M., Gómez-Pesquera, E., Aragón-Camino, M., Liu-Zhu, P., Sánchez-López, A., Hernández-Lozano, A., Peláez-Jareño, M. T., Tamayo, E., Thomas-Rüddel, D. O., Adora, V., Kar, A., Chakraborty, A., Roy, S., Bandyopadhyay, A., Das, M., BenYehudah, G., Salim, M., Kumar, N., Arabi, L., Burger, T., Lephart, P., Toth-martin, E., Valencia, C., Hammami, N., Blot, S., Vincent, J. L., Lambert, M. L., Brunke, J., Riemann, T., Roschke, I., Nimitvilai, S., Jintanapramote, K., Jarupongprapa, S., Adukauskiene, D., Valanciene, D., Bose, G., Lostarakos, V., Carr, B., Khedher, S., Maaoui, A., Ezzamouri, A., Salem, M., Chen, J., Cranendonk, D. R., Day, M., Penrice, G., Roy, K., Robertson, P., Godbole, G., Jones, B., Booth, M., Donaldson, L., Kawano, Y., Ishikura, H., Al-Dorzi, H., Almutairi, M., Alhamadi, B., Crizaldo Toledo, A., Khan, R., Al Raiy, B., Talaie, H., Van Oers, J. A., Harts, A., Nieuwkoop, E., Vos, P., Boussarsar, Y., Boutouta, F., Kamoun, S., Mezghani, I., Koubaji, S., Ben Souissi, A., Riahi, A., Mebazaa, M. S., Giamarellos-Bourboulis, E., Tziolos, N., Routsi, C., Katsenos, C., Tsangaris, I., Pneumatikos, I., Vlachogiannis, G., Theodorou, V., Prekates, A., Antypa, E., Koulouras, V., Kapravelos, N., Gogos, C., Antoniadou, E., Mandragos, K., Armaganidis, A., Robles Caballero, A. R., Civantos, B., Figueira, J. C., López, J., Silva-Pinto, A., Ceia, F., Sarmento, A., Santos, L., Almekhlafi, G., Sakr, Y., Baharoon, S., Aldawood, A., Matroud, A., Alchin, J., Al Johani, S., Balkhy, H., Yousif, S. Y., Alotabi, B. O., Alsaawi, A. S., Ang, J., Curran, M. D., Enoch, D., Navapurkar, V., Morris, A., Sharvill, R., Astin, J., Patel, J., Kruger, C., O’Neal, J., Rhodes, H., Jancik, J., François, B., Laterre, P. F., Eggimann, P., Torres, A., Sánchez, M., Dequin, P. F., Bassi, G. L., Chastre, J., Jafri, H. S., Ben Romdhane, M., Douira, Z., Bousselmi, M., Vakalos, A., Avramidis, V., Craven, T. H., Wojcik, G., Kefala, K., McCoubrey, J., Reilly, J., Paterson, R., Inverarity, D., Laurenson, I., Walsh, T. S., Mongodi, S., Bouhemad, B., Orlando, A., Stella, A., Via, G., Iotti, G., Braschi, A., Mojoli, F., Haliloglu, M., Bilgili, B., Kasapoglu, U., Sayan, I., Süzer Aslan, M., Yalcın, A., Cinel, I., Ellis, H. E., Bauchmuller, K., Miller, D., Temple, A., Luyt, C. E., Singer, M., Nassar, Y., Ayad, M. S., Trifi, A., Abdellatif, S., Daly, F., Nasri, R., Ben Lakhal, S., Gul, F., Kuzovlev, A., Shabanov, A., Polovnikov, S., Kadrichu, N., Dang, T., Corkery, K., Challoner, P., Bassi, G. Li, Aguilera, E., Chiurazzi, C., Travierso, C., Motos, A., Fernandez, L., Amaro, R., Senussi, T., Idone, F., Bobi, J., Rigol, M., Hodiamont, C. J., Janssen, J. M., Bouman, C. S., Mathôt, R. A., De Jong, M. D., Van Hest, R. M., Payne, L., Fraser, G. L., Tudor, B., Lahner, M., Roth, G., Krenn, C., Jault, P., Gabard, J., Leclerc, T., Jennes, S., Que, Y., Rousseau, A., Ravat, F., Eissa, A., Al-Harbi, S., Aldabbagh, T., Abdellatif., S., Paramba, F., Purayil, N., Naushad, V., Mohammad, O., Negi, V., Chandra, P., Kleinsasser, A., Witrz, M. R., Buchner-Doeven, J. F., Tuip-de Boer, A. M., Goslings, J. C., Van Hezel, M., Boing, A, Van Bruggen, R, Juffermans, N, Markopoulou, D., Venetsanou, K., Kaldis, V., Koutete, D., Chroni, D., Alamanos, I., Koch, L., Walter, E., Maekawa, K., Hayakawa, M., Kushimoto, S., Shiraishi, A., Kato, H., Sasaki, J., Matauoka, T., Uejima, T., Morimura, N., Hagiwara, A., Takeda, M., Tarabrin, O., Shcherbakow, S., Gavrychenko, D., Mazurenko, G., Ivanova, V., Chystikov, O., Plourde, C., Lessard, J., Chauny, J., Daoust, R., Kropman, L., In het Panhuis, L., Konings, J., Huskens, D., Schurgers, E., Roest, M., De Laat, B., Lance, M., Durila, M., Lukas, P., Astraverkhava, M., Jonas, J., Budnik, I., Shenkman, B., Hayami, H., Koide, Y., Goto, T., Iqbal, R., Alhamdi, Y., Venugopal, N., Abrams, S., Downey, C., Toh, C. H., Welters, I. D., Bombay, V. B., Chauny, J. M., Daoust, R. D., Lessard, J. L., Marquis, M. M., Paquet, J. P., Siemens, K., Sangaran, D., Hunt, B. J., Durward, A., Nyman, A., Murdoch, I. A., Tibby, S. M., Ampatzidou, F., Moisidou, D., Dalampini, E., Nastou, M., Vasilarou, E., Kalaizi, V., Chatzikostenoglou, H., Drossos, G., Spadaro, S., Fogagnolo, A., Fiore, T., Schiavi, A., Fontana, V., Taccone, F., Volta, C., Chochliourou, E., Volakli, E., Violaki, A., Samkinidou, E., Evlavis, G., Panagiotidou, V., Sdougka, M., Mothukuri, R., Battle, C., Guy, K., Wijesuriya, J., Keogh, S., Docherty, A., O’Donnell, R., Brunskill, S., Trivella, M., Doree, C., Holst, L., Parker, M., Gregersen, M., Almeida, J., Walsh, T., Stanworth, S., Moravcova, S., Mansell, J., Rogers, A., Smith, R. A., Hamilton-Davies, C., Omar, A., Allam, M., Bilala, O., Kindawi, A., Ewila, H., Malamas, A., Ferreira, G., Caldas, J., Fukushima, J., Osawa, E. A., Arita, E., Camara, L., Zeferino, S., Jardim, J., Gaioto, F., Dallan, L., Jatene, F. B., Kalil Filho, R., Galas, F., Hajjar, L. A., Mitaka, C., Ohnuma, T., Murayama, T., Kunimoto, F., Nagashima, M., Takei, T., Tomita, M., Mahmoud, K., Hanoura, S., Sudarsanan, S., Sivadasan, P., Othamn, H., Shouman, Y., Singh, R., Al Khulaifi, A., Mandel, I., Mikheev, S., Suhodolo, I., Kiselev, V., Svirko, Y., Podoksenov, Y., Jenkins, S. A., Griffin, R., Tovar Doncel, M. S., Lima, A., Aldecoa, C., Ince, C., Taha, A., Shafie, A., Mostafa, M., Syed, N., Hon, H., Righetti, F., Colombaroli, E., Castellano, G., Hravnak, M., Chen, L. C., Dubrawski, A. D., Clermont, G. C., Pinsky, M. R., Gonzalez, S., Macias, D., Acosta, J., Jimenez, P., Loza, A., Lesmes, A., Lucena, F., Leon, C., Bastide, M., Richecoeur, J., Frenoy, E., Lemaire, C., Sauneuf, B., Tamion, F., Nseir, S., Du Cheyron, D., Dupont, H., Maizel, J., Shaban, M., Kolko, R., AbuRageila, M., AlHussain, A., Mercado, P., Kontar, L., Titeca, D., Brazier, F., Riviere, A., Joris, M., Soupison, T., De Cagny, B., Slama, M., Wagner, J., Körner, A., Kubik, M., Kluge, S., Reuter, D., Saugel, B., Tran, T., De Bels, D., Cudia, A., Strachinaru, M., Ghottignies, P., Devriendt, J., Pierrakos, C., Martínez González, Ó., Blancas, R., Luján, J., Ballesteros, D., Martínez Díaz, C., Núñez, A., Martín Parra, C., López Matamala, B., Alonso Fernández, M., Chana, M., Huber, W., Eckmann, M., Elkmann, F., Gruber, A., Klein, I., Schmid, R. M., Lahmer, T., Moller, P. W., Sondergaard, S., Jakob, S. M., Takala, J., Berger, D., Bastoni, D., Aya, H., Toscani, L., Pigozzi, L., Rhodes, A., Cecconi, M., Ostrowska, C., Abbas, A., Mellinghoff, J., Ryan, C., Dawson, D., Cronhjort, M., Wall, O., Nyberg, E., Zeng, R., Svensen, C., Mårtensson, J., Joelsson-Alm, E., Parenti, N., Palazzi, C., Amidei, L. A., Borrelli, F. B., Campanale, S. C., Tagliazucchi, F. T., Sedoni, G. S., Lucchesi, D. L., Carella, E. C., Luciani, A. L, Mackovic, M., Maric, N., Bakula, M., Grounds, R. M., Fletcher, N., Avard, B., Zhang, P., Mezidi, M., Charbit, J., Ould-Chikh, M., Deras, P., Maury, C., Martinez, O., Capdevila, X., Hou, P., Linde-Zwirble, W. Z., Douglas, I. D., Shapiro, N. S., Ben Aicha, Y., Laribi, B., Jeribi, B., Pereira, C., Marinho, R., Antunes, R., Marinho, A., Crivits, M., Raes, M., Decruyenaere, J., Hoste, E., Bagin, V., Rudnov, V., Savitsky, A., Astafyeva, M., Korobko, I., Vein, V., Kampmeier, T., Arnemann, P., Hessler, M., Wald, A., Bockbreder, K., Morelli, A., Van Aken, H., Rehberg, S., Ertmer, C., Reddy, S., Bailey, M., Beasley, R., Bellomo, R., Mackle, D., Psirides, A., Young, P., Venkatesh, H., Ramachandran, S., Basu, A., Nair, H., Egan, S., Bates, J., Oliveira, S., Rangel Neto, N. R., Reis, F. Q., Lee, C. P., Lin, X. L., Choong, C., Eu, K. M., Sim, W. Y., Tee, K. S., Pau, J., Abisheganaden, J., Maas, K., De Geus, H., Lafuente, E., Moura, J., Doris, T. E., Monkhouse, D., Shipley, T., Kardasz, S., Gonzalez, I, Stads, S., Groeneveld, A. J., Elsayed, I., Ward, N., Raithatha, A., Steuber, A., Pelletier, C., Schroeder, S., Michael, E., Slowinski, T., Kindgen-Milles, D., Ghabina, S., Turani, F., Belli, A., Busatti, S., Barettin, G., Candidi, F., Gargano, F., Barchetta, R., Falco, M., Demirkiran, O., Kosuk, M., Bozbay, S., Weber, V., Hartmann, J., Harm, S., Linsberger, I., Eichhorn, T., Valicek, G., Miestinger, G., Hoermann, C., Faenza, S., Ricci, D., Mancini, E., Gemelli, C., Cuoghi, A., Magnani, S., Atti, M., Laddomada, T., Doronzio, A., Balicco, B., Gruda, M. C., O’Sullivan, P., Dan, V. P., Guliashvili, T., Scheirer, A., Golobish, T. D., Capponi, V. J., Chan, P. P., Kogelmann, K., Drüner, M., Jarczak, D., Belli, A. B., Martni, S. M., Cotticelli, V. C., Mounajergi, F., Morimoto, S., Hussain, I., Nadeem, A., Ghorab, K., Maghrabi, K., Kloesel, S. K., Goldfuss, C., Stieglitz, A., Stieglitz, A. S., Krstevska, L., Albuszies, G., Jimmy, G., Izawa, J., Iwami, T., Uchino, S., Takinami, M., Kitamura, T., Kawamura, T., Powell-Tuck, J. G., Crichton, S., Raimundo, M., Camporota, L., Wyncoll, D., Ostermann, M., Hana, A., De Geus, H. R., Aydogdu, M., Boyaci, N., Yuksel, S., Gursel, G., Cayci Sivri, A. B., Meza-Márquez, J., Nava-López, J., Carrillo-Esper, R., Dardashti, A., Grubb, A., Wetzstein, M., Peters, E., Njimi, H., Pickkers, P., Waraich, M., Doyle, J., Samuels, T., Forni, L., Desai, N., Baumber, R., Gunning, P., Sell, A., Lin, S., Torrence, H., O’Dwyer, M., Kirwan, C., Prowle, J., Kim, T., O’Connor, M. E., Hewson, R. W., Kirwan, C. J., Pearse, R. M., Maksoud, M., Uzundere, O., Memis, D., Ýnal, M., Gultekin, A., Turan, N., Aydin, M. A., Basar, H., Sencan, I., Kapuagasi, A., Ozturk, M., Uzundurukan, Z., Gokmen, D., Ozcan, A., Kaymak, C., Artemenko, V. A., Budnyuk, A., Pugh, R., Bhandari, S., Mauri, T., Turrini, C., Langer, T., Taccone, P., Volta, C. A., Marenghi, C., Gattinoni, L., Pesenti, A., Sweeney, L., O’Sullivan, A., Kelly, P., Mukeria, E., MacLoughlin, R., Pfeffer, M., Thomas, J. T., Bregman, G. B., Karp, G. K., Kishinevsky, E. K., Stavi, D. S., Adi, N. A., Poropat, T., Knafelj, R., Llopart, E., Batlle, M., De Haro, C., Mesquida, J., Artigas, A., Pavlovic, D., Lewerentz, L., Spassov, A., Schneider, R., De Smet, S., De Raedt, S., Derom, E., Depuydt, P, Oeyen, S., Benoit, D., Gobatto, A., Besen, B., Tierno, P., Melro, L., Mendes, P., Cadamuro, F., Park, M., Malbouisson, L. M., Civantos, B. C., Lopez, J. L., Robles, A., Figueira, J., Yus, S., Garcia, A., Oglinda, A., Ciobanu, G., Oglinda, C., Schirca, L., Sertinean, T., Lupu, V., Wolny, M., Pagano, A., Numis, F., Visone, G., Saldamarco, L., Russo, T., Porta, G., Paladino, F., Bell, C., Liu, J., Debacker, J., Lee, C., Tamberg, E., Campbell, V., Mehta, S., Kara, Ý., Yýldýrým, F., Zerman, A., Güllü, Z., Boyacý, N., Basarýk Aydogan, B., Gaygýsýz, Ü., Gönderen, K., Arýk, G., Turkoglu, M., Aygencel, G., Ülger, Z., Isýkdogan, Z., Özdedeoglu, Ö., Badoglu, M., Gaygýsýz, U., Kongpolprom, N., Sittipunt, C., Eden, A., Kokhanovsky, Y., Bursztein – De Myttenaere, S., Pizov, R., Neilans, L., MacIntyre, N., Radosevich, M., Wanta, B., Meyer, T., Smischney, N., Brown, D., Diedrich, D., Fuller, A., McLindon, P., Sim, K., Shoaeir, M., Noeam, K., Mahrous, A., Matsa, R., Ali, A., Dridi, C., Haddad, F., Pérez-Calatayud, A., Zepeda-Mendoza, A., Diaz-Carrillo, M., Arch-Tirado, E., Carbognin, S., Pelacani, L., Zannoni, F., Agnoli, A., Gagliardi, G., Cho, R., Adams, A., Lunos, S., Ambur, S., Shapiro, R., Prekker, M., Thijssen, M., Janssen, L., Foudraine, N., Voscopoulos, C. J., Freeman, J., George, E., Eversole, D., Muttini, S., Bigi, R., Villani, G., Patroniti, N., Williams, G., George, E, Waldmann, A., Böhm, S., Windisch, W., Strassmann, S., Karagiannidis, C., Karagiannidis, C. K., Waldmann, A. W., Böhm, S. B., Windisch, W. W., Persson, P., Lundin, S., Stenqvist, O., Serra, C. S., Pagano, A. P., Masarone, M. M., Rinaldi, L. R., Amelia, A. A., Fascione, M. F., Adinolfi, L. A., Ruggiero, E. R., Asota, F., O’Rourke, K., Ranjan, S., Morgan, P., DeBacker, J. W., O’Neill, L., Munshi, L., Burry, L., Fan, E., Poo, S., Mahendran, K., Fowles, J., Gerrard, C., Vuylsteke, A., Loveridge, R., Chaddock, C., Patel, S., Kakar, V., Willars, C., Hurst, T., Park, C., Best, T., Vercueil, A., Auzinger, G., Borgman, A., Proudfoot, A. G., Grins, E., Emiley, K. E., Schuitema, J., Fitch, S. J., Marco, G., Sturgill, J., Dickinson, M. G., Strueber, M., Khaghani, A., Wilton, P., Jovinge, S. M., Sampson, C., Harris-Fox, S., Cove, M. E., Vu, L. H., Sen, A., Federspiel, W. J., Kellum, J. A., Mazo Torre, C., Riera, J., Ramirez, S., Borgatta, B., Lagunes, L., Rello, J., Kuzovlev, A. K., Goloubev, A., Nenchuk, S., Karavana, V., Glynos, C., Asimakos, A., Pappas, K., Vrettou, C., Magkou, M., Ischaki, E., Stathopoulos, G., Zakynthinos, S., Kozhevnikova, I., Dalla Corte, F., Grasso, S., Casolari, P., Caramori, G., Andrianjafiarinoa, T., Randriamandrato, T., Rajaonera, T., El-Dash, S., Costa, E. L. V., Tucci, M. R., Leleu, F, Kontar, L, Bacari-Risal, G., Amato, M., El Dash, S., Remmington, Fischer, A., Squire, S., Boichat, M., Honzawa, H., Yasuda, H., Adati, T., Suzaki, S., Horibe, M., Sasaki, M., Sanui, M., Daniel, J., Miranda, H., Milinis, K., Cooper, M., Williams, G. R., McCarron, E., Simants, S., Patanwala, I., Welters, I., Su, Y., Fernández Villanueva, J., Fernández Garda, R., López Lago, A., Rodríguez Ruíz, E., Hernández Vaquero, R., Tomé Martínez de Rituerto, S., Varo Pérez, E., Lefel, N., Schaap, F., Bergmans, D., Olde Damink, S., Van de Poll, M., Tizard, K., Lister, C., Poole, L., Ringaitiene, D., Gineityte, D., Vicka, V., Norkiene, I., Sipylaite, J., O’Loughlin, A., Maraj, V., Dowling, J., Velasco, M. B., Dalcomune, D. M., Dias, E. B., Fernandes, S. L., Oshima, T., Graf, S., Heidegger, C., Genton, L., Karsegard, V., Dupertuis, Y., Pichard, C., Friedli, N., Stanga, Z., Vandersteen, L., Stessel, B., Evers, S., Van Assche, A., Jamaer, L., Dubois, J., Castro, H., Valente, J., Martins, P., Casteloes, P., Magalhaes, C., Cabral, S., Santos, M., Oliveira, B., Salgueiro, A., Duarte, S., Castro, S., Melo, M., Gray, S., Maipang, K., Bhurayanontachai, R., Grädel, L. G., Schütz, P., Langlois, P., Manzanares, W., Lemieux, M., Elke, G., Bloos, F., Heyland, D., Aramendi, I., Babo, N., Hoshino, M., Haraguchi, Y., Kajiwara, S., Mitsuhashi, T., Tsubata, T., Aida, M., Rattanapraphat, T., Kongkamol, C., Xavier, B., Koutsogiannidis, C., Moschopoulou, M., Taskin, G., Çakir, M., Güler, AK, Taskin, A., Öcal, N., Özer, S., Yamanel, L., Wong, J. M., Fitton, C., Anwar, S., Stacey, S., Aggou, M., Fyntanidou, B., Patsatzakis, S., Oloktsidou, E., Lolakos, K., Papapostolou, E., Grosomanidis, V., Gaudry, S., Desailly, V., Pasquier, P., Brun, PB, Tesnieres, AT, Ricard, JD, Dreyfuss, D., Mignon, A., White, J. C, Stilwell, A., Friedlaender, G., Peters, M., Stipulante, S., Delfosse, A., Donneau, AF, Ghuysen, A., Feldmann, C., Freitag, D., Dersch, W., Irqsusi, M., Eschbach, D., Steinfeldt, T., Wulf, H., Wiesmann, T., Cholkraisuwat, J., Beitland, S., Nakstad, E., Stær-Jensen, H., Drægni, T., Andersen, G., Jacobsen, D., Brunborg, C., Waldum-Grevbo, B., Sunde, K., Hoyland, K., Pandit, D., Hayakawa, K., Kotzampassi, K., Loukipoudi, L., Doumaki, E., Admiraal, M. M., Van Assen, M., Van Putten, M. J., Tjepkema-Cloostermans, M., Van Rootselaar, A. F., Ragusa, F., Marudi, A., Baroni, S., Gaspari, A., Bertellini, E., Abdullah, T., Abdel Monem, S., Alcorn, S., McNeill, S., Russell, S., Eertmans, W., Genbrugge, C., Meex, I., Dens, J., Jans, F., De Deyne, C., Avard, B, Burns, R, Patarchi, A., Spina, T., Tanaka, H., Otani, N., Ode, S., Ishimatsu, S., Cho, J., Moon, J. B., Park, C. W., Ohk, T. G., Shin, M. C., Won, M. H., Dakova, S., Ramsheva, Z., Ramshev, K., Marudi, A, Baroni, S, Gaspari, A, Bertellini, E, Ozcan, P. E., Sencer, S., Ulusoy, C., Fallenius, M., Skrifvars, M. B., Reinikainen, M., Bendel, S., Raj, R., Abu-Habsa, M., Hymers, C., Borowska, A., Sivadhas, H., Sahiba, S., Perkins, S., Rubio, J., Rubio, J. A., Sierra, R., English, S., Chasse, M., Turgeon, A., Lauzier, F., Griesdale, D., Garland, A., Fergusson, D., Zarychanski, R., Tinmouth, A., Van Walraven, C., Montroy, K., Ziegler, J., Dupont Chouinard, R., Carignan, R., Dhaliwal, A., Lum, C., Sinclair, J., Pagliarello, G., McIntyre, L., Groza, T., Moreau, N., Castanares-Zapatero, D., Hantson, P., Carbonara, M., Ortolano, F., Zoerle, T., Magnoni, S., Pifferi, S., Conte, V., Stocchetti, N., Carteron, L., Suys, T., Patet, C., Quintard, H., Oddo, M., Spatenkova, V., Pokorna, E., Suchomel, P., Ebert, N., Bylinski, T., Hawthorne, C., Shaw, M., Piper, I., Kinsella, J., Kink, A. K., Rätsep, I. R., Boutin, A., Moore, L., Lacroix, J., Lessard-Bonaventure, P., Turgeon, A. F., Green, R., Erdogan, M., Butler, M., Desjardins, P., Fergusson, D. A., Goncalves, B., Vidal, B., Valdez, C., Rodrigues, A. C., Miguez, L., Moralez, G., Hong, T., Kutz, A., Hausfater, P., Amin, D., Struja, T., Haubitz, S., Huber, A., Brown, T., Collinson, J., Pritchett, C., Slade, T., Le Guen, M., Hellings, S., Ramsaran, R., Alsheikhly, A., Abe, T., Kanapeckaite, L., Bahl, R., Russell, M. Q., Real, K. J., Lyon, R. M., Oveland, N. P., Penketh, J., Mcdonald, M., Kelly, F., Alfafi, M., Almutairi, W., Alotaibi, B., Van den Berg, A. E, Schriel, Y., Dawson, L., Meynaar, I. A., Silva, D., Fernandes, S., Gouveia, J., Santos Silva, J., Foley, J., Kaskovagheorgescu, A., Evoy, D., Cronin, J., Ryan, J., Huck, M., Hoffmann, C., Renner, J., Laitselart, P., Donat, N., Cirodde, A., Schaal, J. V., Masson, Y., Nau, A., Howarth, O., Davenport, K., Jeanrenaud, P., Raftery, S., MacTavish, P., Devine, H., McPeake, J., Daniel, M., Quasim, T., Alrabiee, S., Alrashid, A., Gundogan, O., Bor, C., Akýn Korhan, E., Demirag, K., Uyar, M., Frame, F., Ashton, C., Bergstrom Niska, L., Dilokpattanamongkol, P., Suansanae, T., Suthisisang, C., Morakul, S., Karnjanarachata, C., Tangsujaritvijit, V., Mahmood, S., Al Thani, H., Almenyar, A., Morton, S. E., Chiew, Y. S., Pretty, C., Chase, J. G., Shaw, G. M., Kordis, P., Grover, V., Kuchyn, I., Bielka, K., Aidoni, Z., Stavrou, G., Skourtis, C., Lee, S. D., Williams, K., Weltes, I. D., Berhane, S., Arrowsmith, C., Peters, C., Robert, S., Panerai, R. B., Robinson, T. G., Borg-Seng-Shu, E., De Lima Oliveira, M., Mian, N. C., Nogueira, R., Zeferino, S. P., Jacobsen Teixeira, M., Killeen, P., McPhail, M., Bernal, W., Maggs, J., Wendon, J., Hughes, T., Taniguchi, L. U., Siqueira, E. M., Vieira Jr, J. M., Azevedo, L. C., Ahmad, A. N., Helme, E., Hadfield, S., Shak, J., Senver, C., Howard-Griffin, R., Wacharasint, P., Fuengfoo, P., Sukcharoen, N., Rangsin, R., Sbiti-Rohr, D., Na, H., Song, S., Lee, S., Jeong, E., Lee, K., Zoumpelouli, E., Volakli, E. A, Chrysohoidou, V., Charisopoulou, K., Kotzapanagiotou, E., Manavidou, K., Stathi, Z., AlGhamdi, B., Marashly, Q., Zaza, K., Khurshid, M., Ali, Z., Malgapo, M., Jamil, M., Shafquat, A., Shoukri, M., Hijazi, M., Rocha, F. A., Ebecken, K., Rabello, L. S., Lima, M. F., Hatum, R., De Marco, F. V., Alves, A., Pinto, J. E., Godoy, M., Brasil, P. E., Bozza, F. A., Salluh, J. I., Soares, M., Krinsley, J., Kang, G., Perry, J., Hines, H., Wilkinson, K. M., Tordoff, C., Sloan, B., Bellamy, M. C., Moreira, E., Verga, F., Barbato, M., Burghi, G., Soares, M, Silva, U. V., Torelly, A. P., Kahn, J. M., Angus, D. C., Knibel, M. F., Marshall, R., Gilpin, T., Mota, D., Loureiro, B., Dias, J., Afonso, O., Coelho, F., Martins, A., Faria, F., Al Orainni, H., AlEid, F., Tlaygeh, H., Itani, A., Hejazi, A., Messika, J., Ricard, J. D., Guillo, S., Pasquet, B., Dubief, E., Tubach, F., James, K., Temblett, P., Davies, L., Lynch, C., Pereira, S., Cavaco, S., Fernandes, J., Moreira, I., Almeida, E., Seabra Pereira, F., Malheiro, M., Cardoso, F., Aragão, I., Cardoso, T., Fister, M., Muraray Govind, P., Brahmananda Reddy, N., Pratheema, R., Arul, E. D., Devachandran, J., Chin-Yee, N., D’Egidio, G., Thavorn, K., Kyeremanteng, K., Murchison, A. G., Swalwell, K., Mandeville, J., Stott, D., Guerreiro, I., Goossens, C., Marques, M. B., Derde, S., Vander Perre, S., Dufour, T., Thiessen, S. E., Güiza, F., Janssens, T., Hermans, G., Vanhorebeek, I., De Bock, K., Van den Berghe, G., Langouche, L., Miles, B., Madden, S., Weiler, M., Marques, P., Rodrigues, C., Boeira, M., Brenner, K., Leães, C., Machado, A., Townsend, R., Andrade, J., Kishore, R., Fenlon, C., Fiks, T., Ruijter, A., Te Raa, M., Spronk, P., Docherty, P., Dickson, J., Moltchanova, E., Scarrot, C., Hall, T., Ngu, W. C., Jack, J. M., Pavli, A., Gee, X., Akin Korhan, E., Shirazy, M., Fayed, A., Gupta, S., Kaushal, A., Dewan, S., Varma, A., Ghosh, E., Yang, L., Eshelman, L., Lord, B., Carlson, E., Broderick, R., Ramos, J., Forte, D., Yang, F., Feeney, J., Wilkinson, K., Shuker, K., Faulds, M., Bryden, D., England, L., Shuker, K, Tridente, A, Faulds, M, Matheson, A, Gaynor, J., Bryden, D, Peroni, B., Daglius-Dias, R., Miranda, L., Cohen, C., Carvalho, C., Velasco, I., Kelly, J. M., Neill, A., Rubenfeld, G., Masson, N., Min, A., Boezeman, E., Hofhuis, J., Hovingh, A., De Vries, R., Cabral-Campello, G., Van Mol, M., Nijkamp, M., Kompanje, E., Ostrowski, P., Kiss, K., Köves, B., Csernus, V., Molnár, Z., Hoydonckx, Y., Vanwing, S., Medo, V., Galvez, R., Miranda, J. P., Stone, C., Wigmore, T., Arunan, Y., Wheeler, A., Wong, Y., Poi, C., Gu, C., Molmy, P., Van Grunderbeeck, N., Nigeon, O., Lemyze, M., Thevenin, D., Mallat, J., Correa, M., Carvalho, R. T., Fernandez, A., McBride, C., Koonthalloor, E., Walsh, C., Webber, A., Ashe, M., Smith, K., Volakli, E. A., Dimitriadou, M., Mantzafleri, P., Vrani, O., Arbouti, A., Varsami, T., Bollen, J. A., Van Smaalen, T. C., De Jongh, W. C., Ten Hoopen, M. M., Ysebaert, D., Van Heurn, L. W., Van Mook, W. N., Roze des Ordons, A., Couillard, P., Doig, C., Van Keer, R. V., Deschepper, R. D., Francke, A. F., Huyghens, L. H., Bilsen, J. B., Nyamaizi, B., Dalrymple, C., Dobru, A., Marrinan, E., Ankuli, A., Struthers, R., Crawford, R., Mactavish, P., Morelli, P., Degiovanangelo, M., Lemos, F., MArtinez, V., Cabrera, J., Rutten, A., Van Ieperen, S., De Geer, S., Van Vugt, M., Der Kinderen, E., Giannini, A., Miccinesi, G, Marchesi, T, and Prandi, E

Subjects
Protocol (science), medicine.medical_specialty, business.industry, medicine.medical_treatment, French, 030208 emergency & critical care medicine, Compression (physics), Critical Care and Intensive Care Medicine, Meeting Abstracts, language.human_language, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Ventilation (architecture), Emergency medicine, language, Medicine, 030212 general & internal medicine, Cardiopulmonary resuscitation, business
Abstract

Table of contents P001 - Sepsis impairs the capillary response within hypoxic capillaries and decreases erythrocyte oxygen-dependent ATP efflux R. M. Bateman, M. D. Sharpe, J. E. Jagger, C. G. Ellis P002 - Lower serum immunoglobulin G2 level does not predispose to severe flu. J. Solé-Violán, M. López-Rodríguez, E. Herrera-Ramos, J. Ruíz-Hernández, L. Borderías, J. Horcajada, N. González-Quevedo, O. Rajas, M. Briones, F. Rodríguez de Castro, C. Rodríguez Gallego P003 - Brain protective effects of intravenous immunoglobulin through inhibition of complement activation and apoptosis in a rat model of sepsis F. Esen, G. Orhun, P. Ergin Ozcan, E. Senturk, C. Ugur Yilmaz, N. Orhan, N. Arican, M. Kaya, M. Kucukerden, M. Giris, U. Akcan, S. Bilgic Gazioglu, E. Tuzun P004 - Adenosine a1 receptor dysfunction is associated with leukopenia: A possible mechanism for sepsis-induced leukopenia R. Riff, O. Naamani, A. Douvdevani P005 - Analysis of neutrophil by hyper spectral imaging - A preliminary report R. Takegawa, H. Yoshida, T. Hirose, N. Yamamoto, H. Hagiya, M. Ojima, Y. Akeda, O. Tasaki, K. Tomono, T. Shimazu P006 - Chemiluminescent intensity assessed by eaa predicts the incidence of postoperative infectious complications following gastrointestinal surgery S. Ono, T. Kubo, S. Suda, T. Ueno, T. Ikeda P007 - Serial change of c1 inhibitor in patients with sepsis – A prospective observational study T. Hirose, H. Ogura, H. Takahashi, M. Ojima, J. Kang, Y. Nakamura, T. Kojima, T. Shimazu P008 - Comparison of bacteremia and sepsis on sepsis related biomarkers T. Ikeda, S. Suda, Y. Izutani, T. Ueno, S. Ono P009 - The changes of procalcitonin levels in critical patients with abdominal septic shock during blood purification T. Taniguchi, M. O P010 - Validation of a new sensitive point of care device for rapid measurement of procalcitonin C. Dinter, J. Lotz, B. Eilers, C. Wissmann, R. Lott P011 - Infection biomarkers in primary care patients with acute respiratory tract infections – Comparison of procalcitonin and C-reactive protein M. M. Meili, P. S. Schuetz P012 - Do we need a lower procalcitonin cut off? H. Hawa, M. Sharshir, M. Aburageila, N. Salahuddin P013 - The predictive role of C-reactive protein and procalcitonin biomarkers in central nervous system infections with extensively drug resistant bacteria V. Chantziara, S. Georgiou, A. Tsimogianni, P. Alexandropoulos, A. Vassi, F. Lagiou, M. Valta, G. Micha, E. Chinou, G. Michaloudis P014 - Changes in endotoxin activity assay and procalcitonin levels after direct hemoperfusion with polymyxin-b immobilized fiber A. Kodaira, T. Ikeda, S. Ono, T. Ueno, S. Suda, Y. Izutani, H. Imaizumi P015 - Diagnostic usefullness of combination biomarkers on ICU admission M. V. De la Torre-Prados, A. Garcia-De la Torre, A. Enguix-Armada, A. Puerto-Morlan, V. Perez-Valero, A. Garcia-Alcantara P016 - Platelet function analysis utilising the PFA-100 does not predict infection, bacteraemia, sepsis or outcome in critically ill patients N. Bolton, J. Dudziak, S. Bonney, A. Tridente, P. Nee P017 - Extracellular histone H3 levels are inversely correlated with antithrombin levels and platelet counts and are associated with mortality in sepsis patients G. Nicolaes, M. Wiewel, M. Schultz, K. Wildhagen, J. Horn, R. Schrijver, T. Van der Poll, C. Reutelingsperger P018 - Il-8: is this a more reliable biomarker for sepsis severity than CRP, Procalcitonin, E-selectin, IL-6 and TNF-[alpha] S. Pillai, G. Davies, G. Mills, R. Aubrey, K. Morris, P. Williams, P. Evans P019 - Relation between adrenomedullin and short-term outcome in ICU patients: Results from the frog ICU study E. G. Gayat, J. Struck, A. Cariou, N. Deye, B. Guidet, S. Jabert, J. Launay, M. Legrand, M. Léone, M. Resche-Rigon, E. Vicaut, A. Vieillard-Baron, A. Mebazaa P020 - Impact of disease severity assessment on performance of heparin-binding protein for the prediction of septic shock R. Arnold, M. Capan, A. Linder, P. Akesson P021 - Kinetics and prognostic value of presepsin (sCD14) in septic patients. A pilot study M. Popescu, D. Tomescu P022 - Comparison of CD64 levels performed by the facs and accellix systems C. L. Sprung, R. Calderon Morales, G. Munteanu, E. Orenbuch-Harroch, P. Levin, H. Kasdan, A. Reiter, T. Volker, Y. Himmel, Y. Cohen, J. Meissonnier P023 - Diagnosing sepsis in 5 minutes: Nanofluidic technology study with pancreatic-stone protein (PSP/ reg) L. Girard, F. Rebeaud P024 - How nanotechnology-based approaches could contribute to sepsis prevention, diagnosis and treatment I. Herrmann P025 - Il7r transcriptional expression analysis during septic shock B. Delwarde, E. Peronnet, E. Cerrato, F. Venet, A. Lepape, T. Rimmelé, G. Monneret, J. Textoris P026 - Disbalance of microbial metabolites of aromatic acids affects the severity in critically ill patients N. Beloborodova, V. Moroz, A. Osipov, A. Bedova, Y. Sarshor, A. Pautova, A. Sergeev, E. Chernevskaya P027 - Copeptin predicts 10-year all-cause mortality in community patients J. Odermatt, R. Bolliger, L. Hersberger, M. Ottiger, M. Christ-Crain, B. Mueller, P. Schuetz P028 - Identification of differential proteomic response in septic patients secondary to community and hospital acquired pneumonia N. K. Sharma, A. K. Tashima, M. K. Brunialti, F. R. Machado, M. Assuncao, O. Rigato, R. Salomao P029 - Monocyte HLA-DR expression in community-acquired bacteremic sepsis - dynamics associated to aetiology and prediction of secondary sepsis S. C. Cajander, G. Rasmussen, E. Tina, B. Söderquist, J. Källman, K. Strålin P030 - Soluble B- and T-lymphocyte attenuator: A possible prognostic marker in sepsis A. L. Lange, J. S. Sundén-Cullberg, A. M. Magnuson, O. H. Hultgren P031 - Fractal dimension: A new biomarker for quantifying clot microstructure in patients across the sepsis spectrum G. Davies, S. Pillai, G. Mills, R. Aubrey, K. Morris, P. Williams, P. Evans P032 - Comparison between the new biomarker for coagulation, clot microstructure (Df) with rotational thromboelastometry (ROTEM) in patients across the sepsis spectrum S. Pillai, G. Davies, G. Mills, R. Aubrey, K. Morris, P. Williams, P. Evans P033 - Changes in fibrinolysis across the sepsis spectrum: The use of rotational thromboelastometry (ROTEM) lysis index (LI60) and D-Dimer concentration S. Pillai, G. Davies, G. Mills, R. Aubrey, K. Morris, P. Williams, P. Evans P034 - The intensive care infection score – a promising marker for the prediction of infection and its severity. P. Van der Geest, M. Mohseni, J. Linssen, R. De Jonge, S. Duran, J. Groeneveld P035 - Challenges in the clinical diagnosis of sepsis R. Miller III, B. K. Lopansri, L. C. McHugh, A. Seldon, J. P. Burke P036 - Does zero heat flux thermometry more accurately identify sepsis on intensive care? J. Johnston, R. Reece-Anthony, A. Bond, A. Molokhia P037 - Advancing quality (AQ) sepsis programme: Improving early identification & treatment of sepsis in North West England. C. Mcgrath, E. Nsutebu P038 - Prehospital transport of acute septic patients P. Bank Pedersen, D. Pilsgaard Henriksen, S. Mikkelsen, A. Touborg Lassen P039 - Vasodilatory plant extracts gel as an alternative treatment for fever in critically ill patients R. Tincu, C. Cobilinschi, D. Tomescu, Z. Ghiorghiu, R. Macovei P040 - Host response and outcome of hypothermic sepsis M. A. Wiewel, M. B. Harmon, L. A. Van Vught, B. P. Scicluna, A. J. Hoogendijk, J. Horn, A. H. Zwinderman, O. L. Cremer, M. J. Bonten, M. J. Schultz, T. Van der Poll, N. P. Juffermans, W. J. Wiersinga P041 - Septic shock alert over SIRS criteria has an impact on outcome but needs to be revised G. Eren, Y Tekdos, M. Dogan, O. Acicbe, E. Kaya, O. Hergunsel P042 - Association between previous prescription of βblockers and mortality rate among septic patients: A retrospective observational study S. Alsolamy, G. Ghamdi, L. Alswaidan, S. Alharbi, F. Alenezi, Y. Arabi P043 - Recognition and treatment of sepsis on labour ward– teaching & information resources can improve knowledge J. Heaton, A. Boyce, L. Nolan, J. Johnston, A. Dukoff-Gordon, A. Dean, A. Molokhia P044 - Culture negative sepsis in the ICU – what is unique to this patient population? T. Mann Ben Yehudah P045 - Organ dysfunction in severe sepsis patients identified in administrative data in Germany, 2007-2013 C. Fleischmann, D. Thomas-Rueddel, C. Haas, U. Dennler, K. Reinhart P046 - A comparison of residents’ knowledge regarding; the Surviving Sepsis Campaign 2012 guideline O. Suntornlohanakul, B. Khwannimit P047 - Effectiveness of a septic shock bundle to improve outcomes in the ICU F. Breckenridge, A. Puxty P048 - Dose of norepinephrine in the first 24 hours as a parameter evaluating the effectiveness of treatment in patients with severe sepsis and septic shock P. Szturz, P. Folwarzcny, J. Svancara, R. Kula, P. Sevcik P049 - Norepinephrine or vasopressin + norepinephrine in septic shock. A retrospective series of 39 patients L. Caneva, A. Casazza, E. Bellazzi, S. Marra, L. Pagani, M. Vetere, R. Vanzino, D. Ciprandi, R. Preda, R. Boschi, L. Carnevale P050 - Methylene blue effectiveness as contributory treatment in patients with septic shock V. Lopez, M. Aguilar Arzapalo, L. Barradas, A. Escalante, J. Gongora, M. Cetina P051 - Coagulation disorders in patients with severe sepsis and DIC evaluated with thromboelastometry. B Adamik, D Jakubczyk, A Kübler P052 - Frequency and outcome of early sepsis-associated coagulopathy A. Radford, T. Lee, J. Singer, J. Boyd, D. Fineberg, M. Williams, J. Russell P053 - Assessment of coagulopathy in cancer patients with severe sepsis or septic shock. A case-control pilot study E. Scarlatescu, D. Tomescu, G. Droc, S. Arama P054 - Thromboelastometry in critically ill patients with disseminated intravascular coagulation M. Müller, M. Straat, S. S. Zeerleder, N. P. Juffermans P055 - Cessation of a preexisting chronic antiplatelet therapy is associated with increased mortality rates in severe sepsis and septic shock C. F. Fuchs, C. S. Scheer, S. W. Wauschkuhn, M. V. Vollmer, K. M. Meissner, S. K. Kuhn, K. H. Hahnenkamp, S. R. Rehberg, M. G. Gründling P056 - Neutrophil Extracellular Traps (NETs) production under hypoxic condition N. Yamamoto, M. Ojima, S. Hamaguchi, T. Hirose, Y. Akeda, R. Takegawa, O. Tasaki, T. Shimazu, K. Tomono P057 - Impact of ultraviolet air sterilizer in intensive care unit room, and clinical outcomes of patients E. Gómez-Sánchez, M. Heredia-Rodríguez, E. Álvarez-Fuente, M. Lorenzo-López, E. Gómez-Pesquera, M. Aragón-Camino, P. Liu-Zhu, A. Sánchez-López, A. Hernández-Lozano, M. T. Peláez-Jareño, E. Tamayo P058 - Focus of infection in severe sepsis - comparison of administrative data and prospective cohorts from Germany D. O. Thomas-Rüddel, C. Fleischmann, C. Haas, U. Dennler, K. Reinhart P059 - “Zero CLABSI” – can we get there? Obstacles on the 4 year journey and our strategies to overcome them – experience from an Indian ICU V. Adora, A. Kar, A. Chakraborty, S. Roy, A. Bandyopadhyay, M. Das P060 - Novel molecular techniques to identify central venous catheter (CVC) associated blood stream infections (BSIs) T. Mann Ben Yehudah, G. Ben Yehudah, M. Salim, N. Kumar, L. Arabi, T. Burger, P. Lephart, E. Toth-martin P061 - Zero clabsi” – can we get there? Obstacles on the 4 year journey and our strategies to overcome them – experience from an Indian ICU R. Rao, A. Kar, A. Chakraborty P062 - Prevention of central line-associated bloodstream infections in intensive care units: An international online survey C. Valencia, N. Hammami, S. Blot, J. L. Vincent, M. L. Lambert P063 - 30 days antimicrobial efficacy of non-leaching central venous catheters J. Brunke, T. Riemann, I. Roschke P064 - Efficacy of noble metal alloy-coated catheter in prevention of bacteriuria R. Tincu, C. Cobilinschi, D. Tomescu, Z. Ghiorghiu, R. Macovei P065 - Predicting bacteremic urinary tract infection in community setting: A prospective observational study S. Nimitvilai, K. Jintanapramote, S. Jarupongprapa P066 - Eight-year analysis of acinetobacter spp. monobacteremia in surgical and medical intensive care units at university hospital in Lithuania D. Adukauskiene, D. Valanciene P067 - Group A and group B streptococcal infections in intensive care unit – our experience in a tertiary centre G. Bose, V. Lostarakos, B. Carr P068 - Improved detection of spontaneous bacterial peritonitis by uritop + tm strip test and inoculation of blood culture bottles with ascitic fluid S. Khedher, A. Maaoui, A. Ezzamouri, M. Salem P069 - Increased risk of cellulitis in patients with congestive heart failure: a population based cohort study J. Chen P070 - Outcomes of severe cellulitis and necrotizing fasciitis in the critically ill D. R. Cranendonk, L. A. Van Vught, M. A. Wiewel, O. L. Cremer, J. Horn, M. J. Bonten, M. J. Schultz, T. Van der Poll, W. J. Wiersinga P071 - Botulism outbreak associated with people who inject drugs (PWIDs) in Scotland. M. Day, G. Penrice, K. Roy, P. Robertson, G. Godbole, B. Jones, M. Booth, L. Donaldson P072 - Surveillance of ESBL-producing enterobacteriaceae fecal carriers in the ICU Y. Kawano, H. Ishikura P073 - Prevalence of ESBL and carbapenemase producing uropathogens in a newly opened hospital in south India S. Sreevidya, N. Brahmananda Reddy, P. Muraray Govind, R. Pratheema, J. Devachandran Apollo Speciality Hospital - OMR, Chennai, India P074 - Prevalence, risk factors and outcomes of methicillin-resistant staphylococcus aureus nasal colonization in critically ill patients H. Al-Dorzi, M. Almutairi, B. Alhamadi, A. Crizaldo Toledo, R. Khan, B. Al Raiy, Y. Arabi P075 - Multidrug-resistant Acinetobacter baumannii infection in intensive care unit patients in a hospital with building construction: Is there an association? H. Talaie P076 - Multidrug-resistant organisms in a Dutch ICU J. A. Van Oers, A. Harts, E. Nieuwkoop, P. Vos P077 - Epidemiology and risk factors of ICU acquired infections caused by multidrug-resistant gram negative bacilli Y. Boussarsar, F. Boutouta, S. Kamoun, I. Mezghani, S. Koubaji, A. Ben Souissi, A. Riahi, M. S. Mebazaa P078 - Improving outcomes of severe infections by multidrug-resistant pathogens with polyclonal IgM-enriched immunoglobulins E. Giamarellos-Bourboulis, N. Tziolos, C. Routsi, C. Katsenos, I. Tsangaris, I. Pneumatikos, G. Vlachogiannis, V. Theodorou, A. Prekates, E. Antypa, V. Koulouras, N. Kapravelos, C. Gogos, E. Antoniadou, K. Mandragos, A. Armaganidis P079 - Must change the medical practice in ICU? A. R. Robles Caballero, B. Civantos, J. C. Figueira, J. López P080 - Mediterranean spotted fever in an infectious diseases intensive care unit A. Silva-Pinto, F. Ceia, A. Sarmento, L. Santos P081 - Clinical features and outcomes of patients with Middle East respiratory syndrome requiring admission to a saudi intensive care unit: A retrospective analysis of 31 cases G. Almekhlafi, Y. Sakr P082 - The ICU response to a hospital outbreak of Middle East respiratory syndrome coronavirus infection H. Al-Dorzi, R. Khan, S. Baharoon, A. Aldawood, A. Matroud, J. Alchin, S. Al Johani, H. Balkhy, Y. Arabi P083 - Middle East respiratory syndrome: Surveillance data analysis S. Alsolamy, S. Y. Yousif, B. O. Alotabi, A. S. Alsaawi P085 - Use of Taqman array card molecular diagnostics in severe pneumonia: A case series J. Ang, MD Curran, D. Enoch, V. Navapurkar, A. Conway Morris P086 - ‘BUNS’: An investigation protocol improves the ICU management of pneumonia R. Sharvill, J. Astin P087 - Pneumonia in patients following secondary peritonitis: epidemiological features and impact on mortality M. Heredia-Rodríguez, E. Gómez-Sánchez, M. T. Peláez-Jareño, E. Gómez-Pesquera, M. Lorenzo-López, P. Liu-Zhu, M. Aragón-Camino, A. Hernández-Lozano, A. Sánchez-López, E. Álvarez-Fuente, E. Tamayo P088 - The use of the “CURB-65 score” by emergency room clinicians in a large teaching hospital J. Patel, C. Kruger P089 - Incidence of community acquired pneumonia with viral infection in mechanically ventilated patients in the medical intensive care unit J. O’Neal, H. Rhodes, J. Jancik P090 - The SAATELLITE Study: Prevention of S aureus Nosocomial Pneumonia (NP) with MEDI4893, a Human Monoclonal Antibody (mAb) Against S aureus B. François, P. F. Laterre, P. Eggimann, A. Torres, M. Sánchez, P. F. Dequin, G. L. Bassi, J. Chastre, H. S. Jafri P091 - Risk factors and microbiological profile for nosocomial infections in trauma patients M. Ben Romdhane, Z. Douira, S. Kamoun, M. Bousselmi, A. Ben Souissi, Y. Boussarsar, A. Riahi, M.S. Mebazaa P092 - Correlation between percentages of ventilated patients developed vap and use of antimicrobial agents in ICU patients. A. Vakalos, V. Avramidis P093 - A comparison of two ventilator associated pneumonia surveillance techniques T. H. Craven, G. Wojcik, K. Kefala, J. McCoubrey, J. Reilly, R. Paterson, D. Inverarity, I. Laurenson, T. S. Walsh P094 - Lung ultrasound before and after fiberbronchoscopy - modifications may improve ventilator-associated pneumonia diagnosis S. Mongodi, B. Bouhemad, A. Orlando, A. Stella, G. Via, G. Iotti, A. Braschi, F. Mojoli P095 - Comparing the accuracy of predictors of mortality in ventilator-associated pneumonia M. Haliloglu, B. Bilgili, U. Kasapoglu, I. Sayan, M. Süzer Aslan, A. Yalcın, I. Cinel P096 - Impact of pRBCs transfusion on percentage of ventilated patients developed VAP in ICU patients A. Vakalos, V. Avramidis P097 - The impact of a series of interventions on the rate of ventilator associated pneumonia in a large teaching hospital H. E. Ellis, K. Bauchmuller, D. Miller, A Temple P098 - The EVADE study: Prevention of Nosocomial Pneumonia (NP) caused by P aeruginosa with MEDI3902, a Novel Bispecific Monoclonal Antibody, against P aeruginosa virulence factors J. Chastre, B. François, A. Torres, C. E. Luyt, M. Sánchez, M. Singer, H. S. Jafri P099 - Short-term inhaled colistin adjunctive therapy for ventilator-associated pneumonia Y. Nassar, M. S. Ayad P100 - Effect of aerosolised colistin on weaning from mechanical ventilation A. Trifi, S. Abdellatif, F. Daly, R. Nasri, S. Ben Lakhal P101 - Septic shock is an independent risk factor for colistin-induced severe acute kidney injury: a retrospective cohort study B. Bilgili, M. Haliloglu, F. Gul, I. Cinel P102 - Nosocomial pneumonia - emphasis on inhaled tobramycin A. Kuzovlev, A. Shabanov, S. Polovnikov, V. Moroz P103 - In vitro evaluation of amikacin inhale and commercial nebulizers in a mechanical ventilator N. Kadrichu, T. Dang, K. Corkery, P. Challoner P104 - The effects of nebulized amikacin/fosfomycin and systemic meropenem on severe amikacin-resistant meropenem-susceptible P.aeruginosa pneumonia G. Li Bassi, E. Aguilera, C. Chiurazzi, C. Travierso, A. Motos, L. Fernandez, R. Amaro, T. Senussi, F. Idone, J. Bobi, M. Rigol, A. Torres P105 - Optimization of gentamicin peak concentrations in critically ill patients C. J. Hodiamont, N. P. Juffermans, J. M. Janssen, C. S. Bouman, R. A. Mathôt, M. D. De Jong, R. M. Van Hest P106 - Systematic review of cefepime induced neurotoxicity L. Payne, G. L. Fraser P107 - Unasyn® causes QT prolongation during treatment of intensive care patients B. Tudor, M. Lahner, G. Roth, C. Krenn P108 - Comparative study between teicoplanin and vancomycin in methicillin-resistant staphylococcus aureus (mrsa) infectious of toxicological intensive care unit (ticu) patients – Tehran, Iran H. Talaie P109 - Phage therapy against antimicrobial resistance, design of the first clinical study phagoburn P. Jault, J. Gabard, T. Leclerc, S. Jennes, Y. Que, A. Rousseau, F. Ravat P110 - Antibiotic dosing errors in critically ill patients with severe sepsis or septic shock H. Al-Dorzi, A. Eissa, S. Al-Harbi, T. Aldabbagh, R. Khan, Y. Arabi P111 - Does empiric antifungal therapy improve survival in septic critically ill patients? (immunocompromised excluded) A. Trifi, S. Abdellatif, F. Daly, R. Nasri, S. Ben Lakhal P112 - Neurocysticercosis-Qatar experience F. Paramba, N. Purayil, V. Naushad, O. Mohammad, V. Negi, P. Chandra P113 - Early indicators in acute haemorrhagic shock A. Kleinsasser P114 - Filtering of red blood cells reduces the inflammatory response of pulmonary cells in an in vitro model of mechanical ventilation M. R. Witrz, J. F. Buchner-Doeven, A. M. Tuip-de Boer, J. C. Goslings, N. P. Juffermans P115 - Microparticles from red blood cell transfusion induce a pro-coagulant and pro-inflammatory endothelial cell response M. Van Hezel, M. Straat, A Boing, R Van Bruggen, N Juffermans P116 - The contribution of cytokines on thrombosis development during hospitalization in ICU D. Markopoulou, K. Venetsanou, V. Kaldis, D. Koutete, D. Chroni, I. Alamanos P117 - Prophylactic enoxaparin dosing and adjustment through anti-xa monitoring in an inpatient burn unit L. Koch, J. Jancik, H. Rhodes, E. Walter P118 - Determination of optimal cut-off values of haemoglobin, platelet count and fibrinogen at 24 hours after injury associated with mortality in trauma patients K. Maekawa, M. Hayakawa, S. Kushimoto, A. Shiraishi, H. Kato, J. Sasaki, H. Ogura, T. Matauoka, T. Uejima, N. Morimura, H. Ishikura, A. Hagiwara, M. Takeda P119 - Trauma-induced coagulopathy - prothrombin complex concentrate vs fresh frozen plasma O. Tarabrin, S. Shcherbakow, D. Gavrychenko, G. Mazurenko, V. Ivanova, O. Chystikov P120 - First study to prove the superiority of prothrombin complex concentrates on mortality rate over fresh frozen plasma in patients with acute bleeding C. Plourde, J. Lessard, J. Chauny, R. Daoust P121 - Prothrombin complex concentrate vs fresh frozen plasma in obstetric massive bleeding S. Shcherbakow, O. Tarabrin, D. Gavrychenko, G. Mazurenko, O. Chystikov P122 - Impact of FFP transfusion on VAP in ICU patients A. Vakalos, V. Avramidis P123 - Preoperative platelet function test and the thrombin generation assay are predictive for blood loss after cardiac surgery L. Kropman, L. In het Panhuis, J. Konings, D. Huskens, E. Schurgers, M. Roest, B. De Laat, M. Lance P124 - Rotational thromboelastometry versus standard coagulation tests before surgical interventions M. Durila, P. Lukas, M. Astraverkhava, J. Jonas P125 - Correction of impaired clot quality and stability by fibrinogen and activated prothrombin complex concentrate in a model of severe thrombocytopenia I. Budnik, B. Shenkman P126 - Assessment of point-of-care prothrombin time analyzer as a monitor after cardiopulmonary bypass H. Hayami, Y. Koide, T. Goto P127 - Disseminated intravascular coagulation (dic) is underdiagnosed in critically ill patients: do we need d-dimer measurements? R. Iqbal, Y. Alhamdi, N. Venugopal, S. Abrams, C. Downey, C. H. Toh, I. D. Welters P128 - Validity of the age-adjusted d-dimer cutoff in patients with COPD B. Bombay, J. M. Chauny, R. D. Daoust, J. L. Lessard, M. M. Marquis, J. P. Paquet P129 - A scoping review of strategies for prevention and management of bleeding following paediatric cardiopulmonary bypass surgery K. Siemens, D. Sangaran, B. J. Hunt, A. Durward, A. Nyman, I. A. Murdoch, S. M. Tibby P130 - Nadir hemoglobulin during cardiopulmonary bypass: impact on postoperative morbidity and mortality F. Ampatzidou, D. Moisidou, E. Dalampini, M. Nastou, E. Vasilarou, V. Kalaizi, H. Chatzikostenoglou, G. Drossos P131 - Red blood cell transfusion do not influence the prognostic value of RDW in critically ill patients S. Spadaro, A. Fogagnolo, T. Fiore, A. Schiavi, V. Fontana, F. Taccone, C. Volta P132 - Reasons for admission in the paediatric intensive care unit and the need for blood and blood products transfusions E. Chochliourou, E. Volakli, A. Violaki, E. Samkinidou, G. Evlavis, V. Panagiotidou, M. Sdougka P133 - The implementation of a massive haemorrhage protocol (mhp) for the management of major trauma: a ten year, single-centre study R. Mothukuri, C. Battle, K. Guy, G. Mills, P. Evans P134 - An integrated major haemorrhage protocol for pre-hospital and retrieval medical teams J. Wijesuriya, S. Keogh P135 - The impact of transfusion thresholds on mortality and cardiovascular events in patients with cardiovascular disease (non-cardiac surgery): a systematic review and meta-analysis A. Docherty, R. O’Donnell, S. Brunskill, M. Trivella, C. Doree, L. Holst, M. Parker, M. Gregersen, J. Almeida, T. Walsh, S. Stanworth P136 - The relationship between poor pre-operative immune status and outcome from cardiac surgery is specific to the peri-operative antigenic threat S. Moravcova, J. Mansell, A. Rogers, R. A. Smith, C. Hamilton-Davies P137 - Impact of simple clinical practice guidelines for reducing post-operative atrial fibrillation after cardiac surgery. A. Omar, M. Allam, O. Bilala, A. Kindawi, H. Ewila P138 - Dexamethasone administration during cardiopulmonary bypass has no beneficial effects on elective postoperative cardiac surgery patients F. Ampatzidou, D. Moisidou, M. Nastou, E. Dalampini, A. Malamas, E. Vasilarou, G. Drossos P139 - Intra-aortic balloon counterpulsation in patients undergoing cardiac surgery (IABCS): preliminary results G. Ferreira, J. Caldas, J. Fukushima, E. A. Osawa, E. Arita, L. Camara, S. Zeferino, J. Jardim, F. Gaioto, L. Dallan, F. B. Jatene, R. Kalil Filho, .F Galas, L. A. Hajjar P140 - Effects of low-dose atrial natriuretic peptide infusion on cardiac surgery-associated acute kidney injury C. Mitaka, T. Ohnuma, T. Murayama, F. Kunimoto, M. Nagashima, T. Takei, M. Tomita P141 - Acute kidney injury influence on high sensitive troponin measurements after cardiac surgery A. Omar, K. Mahmoud, S. Hanoura, S. Sudarsanan, P. Sivadasan, H. Othamn, Y. Shouman, R. Singh, A. Al Khulaifi P142 - Complex evaluation of endothelial dysfunction markers for prognosis of outcomes in patients undergoing cardiac surgery I. Mandel, S. Mikheev, I. Suhodolo, V. Kiselev, Y. Svirko, Y. Podoksenov P143 - New-onset atrial fibrillation in intensive care: incidence, management and outcome S. A. Jenkins, R. Griffin P144 - One single spot measurement of the sublingual microcirculation during acute pulmonary hypertension in a pig model of shock M. S. Tovar Doncel, A. Lima, C. Aldecoa, C. Ince P145 - Assessment of levosimendan as a therapeutic option to recruit the microcirculation in cardiogenic shock – initial experience in cardiac ICU A. Taha, A. Shafie, M. Mostafa, N. Syed, H. Hon P146 - Terlipressin vs. norepinephrine in the Potential Multiorgan Donor(PMD) F. Righetti, E. Colombaroli, G. Castellano P147 - Echocardiography in the potential heart donor exposed to substitution hormonotherapy F. Righetti, E. Colombaroli P148 - Machine learning can reduce rate of monitor alarms M. Hravnak, L. C. Chen, A. D. Dubrawski, G. C. Clermont, M. R. Pinsky P149 - Peripherally inserted central catheters placed in the ICU S. Gonzalez, D. Macias, J. Acosta, P. Jimenez, A. Loza, A. Lesmes, F. Lucena, C. Leon P150 - Recordings of abnormal central venous pressure waveform morphology during an episode of pulmonary hypertension in a porcine shock model M. S. Tovar Doncel, C. Ince, C. Aldecoa, A. Lima P151 - Ultrasound guided central venous access technique among French intensivists M. Bastide, J. Richecoeur, E. Frenoy, C. Lemaire, B. Sauneuf, F. Tamion, S. Nseir, D. Du Cheyron, H. Dupont, J. Maizel P152 - Predictive ability of the Pv-aCO2 gap in patients with shock M. Shaban, R. Kolko, N. Salahuddin, M. Sharshir, M. AbuRageila, A. AlHussain P153 - Comparison of echocardiography and pulmonary artery catheter measurements of hemodynamic parameters in critical ill patients P. Mercado, J. Maizel, L. Kontar, D. Titeca, F. Brazier, A. Riviere, M. Joris, T. Soupison, B. De Cagny, M. Slama P154 - The volume clamp method for noninvasive cardiac output measurement in postoperative cardiothoracic surgery patients: a comparison with intermittent pulmonary artery thermodilution J. Wagner, A. Körner, M. Kubik, S. Kluge, D. Reuter, B. Saugel P155 - Hemodynamic monitoring in patients with septic shock (SS) – CPCCO (continuous pulse contour cardiac output) vs. TEE (transesophageal echocardiography) E. Colombaroli, F. Righetti, G. Castellano P156 - Cardiac output measurement with transthoracic echocardiography in critically ill patients: a pragmatic clinical study T. Tran, D. De Bels, A. Cudia, M. Strachinaru, P. Ghottignies, J. Devriendt, C. Pierrakos P157 - Left ventricular outflow tract velocity time integral correlates with stroke volume index in mechanically ventilated patients Ó. Martínez González, R. Blancas, J. Luján, D. Ballesteros, C. Martínez Díaz, A. Núñez, C. Martín Parra, B. López Matamala, M. Alonso Fernández, M. Chana P158 - Transpulmonary thermodilution (TPTD) derived from femoral vs. jugular central venous catheter: validation of a previously published correction formula and a proprietary correction formula for global end-diastolic volume index (GEDVI) W. Huber, M. Eckmann, F. Elkmann, A. Gruber, I. Klein, R. M. Schmid, T. Lahmer P160 - Dynamic arterial elastance calculated with lidcoplus monitor does not predict changes in arterial pressure after a fluid challenge in postsurgical patients D. Bastoni, H. Aya, L. Toscani, L. Pigozzi, A. Rhodes, M. Cecconi P159 - Venous return driving pressure and resistance in acute blood volume changes P. W. Moller, S. Sondergaard, S. M. Jakob, J. Takala, D. Berger P160 - Dynamic arterial elastance calculated with lidcoplus monitor does not predict changes in arterial pressure after a fluid challenge in postsurgical patients D. Bastoni, H. Aya, L. Toscani, L. Pigozzi, A. Rhodes, M. Cecconi P161 - Analysis of duration of post-operative goal-directed therapy protocol C. Ostrowska, H. Aya, A. Abbas, J. Mellinghoff, C. Ryan, D. Dawson, A. Rhodes, M. Cecconi P162 - Hemodynamic optimization – back to square one? M. Cronhjort, O. Wall, E. Nyberg, R. Zeng, C. Svensen, J. Mårtensson, E. Joelsson-Alm P163 - Effectiveness of fluid thoracic content measurement by bioimpedance guiding intravascular volume optimization in patients with septic shock M. Aguilar Arzapalo, L. Barradas, V. Lopez, M. Cetina P164 - A systematic review on the role of internal jugular vein ultrasound measurements in assessment of volume status in critical shock patients N. Parenti, C. Palazzi, L. A. Amidei, F. B. Borrelli, S. C. Campanale, F. T. Tagliazucchi, G. S. Sedoni, D. L. Lucchesi, E. C. Carella, A. L Luciani P165 - Importance of recognizing dehydration in medical Intensive Care Unit M. Mackovic, N. Maric, M. Bakula P166 - Effect of volume for a fluid challenge in septic patients H. Aya, A. Rhodes, R. M. Grounds, N. Fletcher, M. Cecconi P167 - Fluid bolus practices in a large Australian intensive care unit B. Avard, P. Zhang P168 - Liberal late fluid management is associated with longer ventilation duration and worst outcome in severe trauma patients: a retrospective cohort of 294 patients M. Mezidi, J. Charbit, M. Ould-Chikh, P. Deras, C. Maury, O. Martinez, X. Capdevila P169 - Association of fluids and outcomes in emergency department patients hospitalized with community-acquired pneumonia P. Hou, W. Z. Linde-Zwirble, I. D. Douglas, N. S. Shapiro P170 - Association of positive fluid balance with poor outcome in medicosurgical ICU patients A. Ben Souissi, I. Mezghani, Y. Ben Aicha, S. Kamoun, B. Laribi, B. Jeribi, A. Riahi, M. S. Mebazaa P171 - Impact of fluid balance to organ dysfunction in critically ill patients C. Pereira, R. Marinho, R. Antunes, A. Marinho P172 - Volume bolus in ICU patients: do we need to balance our crystalloids? M. Crivits, M. Raes, J. Decruyenaere, E. Hoste P173 - The use of 6 % HES solution do not reduce total fluid requirement in the therapy of patients with burn shock V. Bagin, V. Rudnov, A. Savitsky, M. Astafyeva, I. Korobko, V. Vein P174 - Electron microscopic assessment of acute kidney injury in septic sheep resuscitated with crystalloids or different colloids T. Kampmeier , P. Arnemann, M. Hessler, A. Wald, K. Bockbreder, A. Morelli, H. Van Aken, S. Rehberg, C. Ertmer P175 - Alterations of conjunctival microcirculation in a sheep model of haemorrhagic shock and resuscitation with 0.9 % saline or balanced tetrastarch P. Arnemann, M. Hessler, T. Kampmeier, S. Rehberg, H. Van Aken, C. Ince, C. Ertmer P176 - A single centre nested pilot study investigating the effect of using 0.9 % saline or Plasma-Lyte 148 ® as crystalloid fluid therapy on gastrointestinal feeding intolerance in mechanically ventilated patients receiving nasogastric enteral nutrition S. Reddy, M. Bailey, R. Beasley, R. Bellomo, D. Mackle, A. Psirides, P. Young P177 - A single centre nested pilot study investigating the effect on post-operative bleeding of using 0.9 % saline or Plasma-Lyte® 148 as crystalloid fluid therapy in adults in ICU after heart surgery S. Reddy, M. Bailey, R. Beasley, R. Bellomo, D. Mackle, P. Young P178 - Extreme hypernatremia and sepsis in a patient with Huntington’s dementia: a conundrum in fluid management H. Venkatesh, S. Ramachandran, A. Basu, H. Nair P179 - Diagnosis and management of severe hypernatraemia in the critical care setting S. Egan, J. Bates P180 - Correlation between arterial blood gas and electrolyte disturbances during hospitalization and outcome in critically ill patients S. Oliveira, N. R. Rangel Neto, F. Q. Reis P181 - Missing the “I” in MUDPILES – a rare cause of high anion gap metabolic acidosis (HAGMA) C. P. Lee, X. L. Lin, C. Choong , K. M. Eu, W. Y. Sim , K. S. Tee, J. Pau , J. Abisheganaden P182 - Plasma NGAL and urinary output: potential parameters for early initiation of renal replacement therapy K. Maas, H. De Geus P183 - Renal replacement therapy for critically ill patients: an intermittent continuity E. Lafuente, R. Marinho, J. Moura, R. Antunes, A. Marinho P184 - A survey of practices related to renal replacement therapy in critically ill patients in the north of England. T. E. Doris, D. Monkhouse, T. Shipley, S. Kardasz, I Gonzalez P185 - High initiation creatinine associated with lower 28-day mortality in critically ill patients necessitating continuous renal replacement therapy S. Stads, A. J. Groeneveld P186 - The impact of Karnofsky performance scale on outcomes in acute kidney injury patients receiving renal replacement therapy on the intensive care unit I. Elsayed, N. Ward, A. Tridente, A. Raithatha P187 - Severe hypophosphatemia during citrate-anticoagulated CRRT A. Steuber, C. Pelletier, S. Schroeder, E. Michael, T. Slowinski, D. Kindgen-Milles P188 - Citrate regional anticoagulation for post dilution continuous renal replacement therapy S. Ghabina P189 - Citrate 18 mmol/l improves anticoagulation during RRT with adsorbing filters F. Turani, A. Belli, S. Busatti, G. Barettin, F. Candidi, F. Gargano, R. Barchetta, M. Falco P190 - Calcium gluconate instead of calcium chloride in citrate-anticoagulated CVVHD O. Demirkiran, M. Kosuk, S. Bozbay P191 - Enhanced clearance of interleukin-6 with continuous veno-venous haemodialysis (CVVHD) using Ultraflux EMiC2 vs. Ultraflux AV1000S V. Weber, J. Hartmann, S. Harm, I. Linsberger, T. Eichhorn, G. Valicek, G. Miestinger, C. Hoermann P192 - Removal of bilirubin with a new adsorbent system: in vitro kinetics S. Faenza, D. Ricci, E. Mancini, C. Gemelli, A. Cuoghi, S. Magnani, M. Atti P193 - Case series of patients with severe sepsis and septic shock treated with a new extracorporeal sorbent T. Laddomada, A. Doronzio, B. Balicco P194 - In vitro adsorption of a broad spectrum of inflammatory mediators with CytoSorb® hemoadsorbent polymer beads M. C. Gruda, P. O’Sullivan, V. P. Dan, T. Guliashvili, A. Scheirer, T. D. Golobish, V. J. Capponi, P. P. Chan P195 - Observations in early vs. late use of cytosorb therapy in critically ill patients K. Kogelmann, M. Drüner, D. Jarczak P196 - Oxiris membrane decreases endotoxin during rrt in septic patients with basal EAA > 0,6 F. Turani, A. B. Belli, S. M. Martni, V. C. Cotticelli, F. Mounajergi, R. Barchetta P197 - An observational prospective study on the onset of augmented renal clearance: the first report S. Morimoto, H. Ishikura P198 - An ultrasound- guided algorithm for the management of oliguria in severe sepsis I. Hussain, N. Salahuddin, A. Nadeem, K. Ghorab, K. Maghrabi P199 - Ultrasound in acute kidney injury (aki). First findings of farius, an education-programme in structural ultrasonography S. K. Kloesel, C. Goldfuss, A. Stieglitz, A. S. Stieglitz, L. Krstevska, G. Albuszies P200 - Effectiveness of renal angina index score predicting acute kidney injury on critically ill patients M. Aguilar Arzapalo, L. Barradas, V. Lopez, A. Escalante, G. Jimmy, M. Cetina P201 - Time length below blood pressure thresholds and progression of acute kidney injury in critically ill patients with or without sepsis: a retrospective, exploratory cohort study J. Izawa, T. Iwami, S. Uchino, M. Takinami, T. Kitamura, T. Kawamura P202 - Anaemia does not affect renal recovery in acute kidney injury J. G. Powell-Tuck, S. Crichton, M. Raimundo, L. Camporota, D. Wyncoll, M. Ostermann P203 - Estimated glomerular filtration rate based on serum creatinine: actual practice in Dutch ICU’s A. Hana, H. R. De Geus P204 - Comparison of estimated glomerular filtration rate calculated by mdrd, ckd-epi-serum-creatinine and ckd-epi-cystatin-c in adult critically ill patients H. R. De Geus, A. Hana P205 - Early diagnosis of septic acute kidney injury in medical critical care patients with a urine cell cycle arrest marker: insulin like growth factor binding protein-7 (IGFBP-7) M. Aydogdu, N. Boyaci, S. Yuksel, G. Gursel, A. B. Cayci Sivri P206 - Urinary neutrophil gelatinase-associated lipocalin as early biomarker of severe acute kidney injury in intensive care J. Meza-Márquez, J. Nava-López, R. Carrillo-Esper P207 - Shrunken pore syndrome is associated with a sharp rise in mortality in patients undergoing elective coronary artery bypass grafting A. Dardashti, A. Grubb P208 - The biomarker nephrocheck™ can discriminate the septic shock patients with an akin 1 or 2 acute renal failure who will not progress toward the akin 3 level J. Maizel, M. Wetzstein, D. Titeca, L. Kontar, F. Brazier, B. De Cagny, A. Riviere, T. Soupison, M. Joris, M. Slama P209 - A worldwide multicentre evaluation of acute kidney injury in septic and non-septic critically ill patients: the intensive care over nations (icon) audit E. Peters, H. Njimi, P. Pickkers, J. L. Vincent P210 - Does enhanced recovery after surgery reduce the incidence of acute kidney injury in those undergoing major gynae-oncological surgery? M. Waraich , J. Doyle, T. Samuels, L. Forni P211 - Identification of risk factors for the development of acute kidney injury after lower limb arthroplasty N. Desai, R. Baumber, P. Gunning, A. Sell P212 - Incidences and associations of acute kidney injury after major trauma S. Lin, H. Torrence, M. O’Dwyer, C. Kirwan, J. Prowle P213 - Acute kidney injury of major trauma patients T Kim P214 - Trajectory of serum creatinine after major surgery and the diagnosis of acute kidney injury M. E. O’Connor, R. W. Hewson, C. J. Kirwan, R. M. Pearse, J. Prowle P215 - Epidemiology of acute kidney injury after cardiac surgery. A single center retrospective study S. Hanoura , A. Omar, H. Othamn, S. Sudarsanan , M. Allam, M. Maksoud, R. Singh, A. Al Khulaifi P216 - Post-operative acute kidney injury after major non-cardiac surgery and its association with death in the following year M. E. O’Connor, R. W. Hewson, C. J. Kirwan, R. M. Pearse, J. Prowle P217 - Factors affecting acute renal failure in intensive care unit and effect of these factors on mortality O. Uzundere, D. Memis , M. Ýnal, A. , N. Turan P218 - Results of the live kidney transplantations according to national data of turkish organ and tissue information system M. A. Aydin, H. Basar, I. Sencan, A. Kapuagasi, M. Ozturk, Z. Uzundurukan, D. Gokmen, A. Ozcan, C. Kaymak P219 - Anaesthesia procedure and intensive therapy in patients with neck phlegmon V. A. Artemenko, A. Budnyuk P220 - Nasal high flow oygen for acute respiratory failure: a systematic review R. Pugh , S. Bhandari P221 - Setting optimal flow rate during high flow nasal cannula support: preliminary results T. Mauri, C. Turrini, T. Langer, P. Taccone, C. A. Volta, C. Marenghi, L. Gattinoni, A. Pesenti P222 - Dose to dose consistency across two different gas flow rates using cystic fibrosis and normal adult breathing profiles during nasal high flow oxygen therapy L. Sweeney, A . O’ Sullivan, P. Kelly, E. Mukeria, R. MacLoughlin P223 - Final results of an evaluation of airway medix closed suction system compared to a standard closed suction system M. Pfeffer, J. T. Thomas, G. B. Bregman, G. K. Karp, E. K. Kishinevsky, D. S. Stavi, N. A. Adi P224 - Different cuff materials and different leak tests - one size does not fit all T. Poropat, R. Knafelj P225 - Observational study on the value of the cuff-leak test and the onset of upper airway obstruction after extubation E. Llopart, M. Batlle, C. De Haro, J. Mesquida, A. Artigas P226 - A device for emergency transtracheal lung ventilation D. Pavlovic, L. Lewerentz, A. Spassov, R. Schneider P227 - Long-term outcome and health-related quality of life in patients discharged from the intensive care unit with a tracheostomy and with or without prolonged mechanical ventilation S. De Smet, S. De Raedt, E. Derom, P Depuydt, S. Oeyen, D. Benoit, J. Decruyenaere P228 - Ultrasound-guided percutaneous dilational tracheostomy versus bronchoscopy-guided percutaneous dilational tracheostomy in critically ill patients (trachus): a randomized clinical trial A. Gobatto, B. Bese, P. Tierno, L. Melro, P. Mendes, F. Cadamuro, M. Park, L. M. Malbouisson P229 - Is it safe to discharge patients with tracheostomy from the ICU to the ward? B. C. Civanto, J. L. Lopez, A. Robles, J. Figueira, S. Yus, A. Garcia P230 - The application of tracheostomy in children in ICU A. Oglinda, G. Ciobanu, C. Oglinda, L. Schirca, T. Sertinean, V. Lupu P231 - The impact of passive humidifiers on aerosol drug delivery during mechanical ventilation P. Kelly, A. O’Sullivan, L. Sweeney, R. MacLoughlin P232 - Evaluation of vibrating mesh and jet nebuliser performance at two different attachment setups in line with a humidifier nebuliser system A. O’Sullivan, P. Kelly, L. Sweeney, E. Mukeria, M. Wolny , R. MacLoughlin P233 - Psv-niv versus cpap in the treatment of acute cardiogenic pulmonary edema A. Pagano, F. Numis, G. Vison, L. Saldamarco, T. Russo, G. Porta, F. Paladino P234 - Noninvasive ventilation in patients with haematologic malignancy: a retrospective review C. Bell, J. Liu, J. Debacker, C. Lee, E. Tamberg, V. Campbell, S. Mehta P235 - Use of non-invasive ventilation in infectious diseases besides classical indications A. Silva-Pinto, A. Sarmento, L. Santos P236 - The impact of fragility on noninvasive mechanical ventilation application and results in the ICU Ý. Kara, F. Yýldýrým, A. Zerman, Z. Güllü, N. Boyacý, B. Basarýk Aydogan, Ü. Gaygýsýz, K. Gönderen, G. Arýk, M. Turkoglu, M. Aydogdu, G. Aygencel, Z. Ülger, G. Gursel P237 - Effects of metabolic alkalosis on noninvasive ventilation success and ICU outcome in patients with hypercapnic respiratory failure N. Boyacý, Z. Isýkdogan, Ö. Özdedeoglu, Z. Güllü, M. Badoglu, U. Gaygýsýz, M. Aydogdu, G. Gursel P238 - Asynchrony index and breathing patterns of acute exacerbation copd patients assisted with noninvasive pressure support ventilation and neurally adjusted ventilatory assist N. Kongpolprom, C. Sittipunt P239 - High frequency jet ventilation for severe acute hypoxemia A. Eden, Y. Kokhanovsky, S. Bursztein – De Myttenaere, R. Pizov P240 - HFOV revisited: a 7 year retrospective analysis of patients receiving HFOV who met oscillate trial entry criteria L. Neilans, N. MacIntyre P241 - Implementation of a goal-directed mechanical ventilation order set driven by respiratory therapists can improve compliance with best practices for mechanical ventilation M. Radosevich, B. Wanta, V. Weber, T. Meyer, N. Smischney, D. Brown, D. Diedrich P242 - A reduction in tidal volumes for ventilated patients on ICU calculated from IBW. can it minimise mortality in comparison to traditional strategies? A . Fuller, P. McLindon, K. Sim P243 - Predictive value of lung aeration scoring using lung ultrasound in weaning failure M. Shoaeir, K. Noeam, A. Mahrous, R. Matsa, A. Ali P244 - Conventional versus automated weaning from mechanical ventilation using SmartCare™ C. Dridi, S. Koubaji, S. Kamoun, F. Haddad, A. Ben Souissi, B. Laribi, A. Riahi, M. S. Mebazaa P245 - Ultrasonographic evaluation protocol for weaning from mechanichal ventilation A. Pérez-Calatayud, R. Carrillo-Esper, A. Zepeda-Mendoza, M. Diaz-Carrillo, E. Arch-Tirado P246 - Diaphragm ultrasonography: a method for weaning patients from mechanical ventilation S. Carbognin, L. Pelacani, F. Zannoni, A. Agnoli, G. Gagliardi P247 - Dorsal diaphragmatic excursion tracks transpulmonary pressure in ventilated ARDS patients: a potential non-invasive indicator of lung recruitment? R. Cho, A. Adams , S. Lunos, S. Ambur, R. Shapiro, M. Prekker P248 - Pulse oximetry in the icu patient: is the perfusion index of any value? M. Thijssen, L. Janssen, N. Foudraine P249 - Ventilation is a better assessment of respiratory status than EtCO2 C. J. Voscopoulos, J. Freeman P250 - Evaluation of the relationship between non-invasive minute ventilation and end-tidal CO2 in patients undergoing general vs spinal anesthesia C. J. Voscopoulos, J. Freeman, E. George P251 - Respiratory volume monitoring provides early warning of respiratory depression and can be used to reduce false alarms in non-intubated patients C. J. Voscopoulos, D. Eversole, J. Freeman, E. George P252 - P/i index: a predictive edi-derived weaning index during nava S. Muttini, R. Bigi, G. Villani, N. Patroniti P253 - Adequacy of ventilation in patients receiving opioids in the post anesthesia care unit: minute ventilation versus respiratory rate G. Williams, C. J. Voscopoulos, J. Freeman, E. George P254 - Comparison of regional and global expiratory time constants measured by electrical impedance tomography (EIT) A. Waldmann, S. Böhm, W. Windisch, S. Strassmann, C. Karagiannidis P255 - Electrical impedance tomography: robustness of a new pixel wise regional expiratory time constant calculation A. Waldmann, S. Böhm, W. Windisch, S. Strassmann, C. Karagiannidis P256 - Validation of regional and global expiratory time constant measurement by electrical impedance tomography in ards and obstructive pulmonary diseases C. K. Karagiannidis, A. W. Waldmann, S. B. Böhm, S. Strassmann, W. W. Windisch P257 - Transpulmonary pressure in a model with elastic recoiling lung and expanding chest wall P. Persson, S. Lundin, O. Stenqvist P258 - Lactate in pleural and abdominal effusion G. Porta, F. Numis, C. S. Serra, A. P. Pagano, M. M. Masarone, L. R. Rinaldi, A. A. Amelia, M. F. Fascione, L. A. Adinolfi, E. R. Ruggiero P259 - Outcome of patients admitted to the intensive care with pulmonary fibrosis F. Asota, K. O’Rourke, S. Ranjan, P. Morgan P260 - Sedation and analgesia practice in extra-corporeal membrane oxygenation (ECMO)-treated patients with acute respiratory distress syndrome (ARDS): a retrospective study J. W. DeBacker, E. Tamberg, L. O’Neill, L. Munshi, L. Burry, E. Fan, S. Mehta P261 - Characteristics and outcomes of patients deemed not eligible when referred for veno-venous extracorporeal membrane oxygenation (vv-ECMO) S. Poo, K. Mahendran, J. Fowles, C. Gerrard, A. Vuylsteke P262 - The SAVE SMR for veno-arterial ECMO R. Loveridge, C. Chaddock, S. Patel, V. Kakar, C. Willars, T. Hurst, C. Park, T. Best, A. Vercueil, G. Auzinger P263 - A simplified score to predict early (48 h) mortality in patients being considered for VA-ECMO A. Borgman, A. G. Proudfoot, E. Grins, K. E. Emiley, J. Schuitema, S. J. Fitch, G. Marco, J. Sturgill, M. G. Dickinson, M. Strueber, A. Khaghani, P. Wilton, S. M. Jovinge P264 - Lung function six months post extra corporeal membrane oxygenation (ECMO) for severe acute respiratory failure in adult survivors C. Sampson, S. Harris-Fox P265 - Bicarbonate dialysis removes carbon dioxide in hypoventilated rodents. M. E. Cove, L. H. Vu, A. Sen, W. J. Federspiel, J. A. Kellum P266 - Procalcitonin as predictor of primary graft dysfunction and mortality in post-lung transplantation C. Mazo Torre, J. Riera, S. Ramirez, B. Borgatta, L. Lagunes, J. Rello P267 - New molecular biomarkers of acute respiratory distress syndrome in abdominal sepsis A. K. Kuzovlev, V. Moroz, A. Goloubev, S. Polovnikov, S. Nenchuk P268 - Tight junction’s proteins claudin -5 and regulation by tnf in experimental murine lung injury model of ali/ards V. Karavana, C. Glynos, A. Asimakos, K. Pappas, C. Vrettou, M. Magkou, E. Ischaki, G. Stathopoulos, S. Zakynthinos P269 - Cell counts in endobronchial aspirate to assess airway inflammation in ARDS patients: a pilot study S. Spadaro, I. Kozhevnikova, F. Dalla Corte, S. Grasso, P. Casolari, G. Caramori, C. Volta P270 - Epidemiological and clinical profile of patients with acute respiratory distress syndrome in the surgical intensive care unit surgical, hospital JRA, Antananarivo T. Andrianjafiarinoa, T. Randriamandrato, T. Rajaonera P271 - Effect of high PEEP after recruitment maneuver on right ventricular function in ARDS. Is it good for the lung and for the heart? S. El-Dash, ELV Costa, MR Tucci, F Leleu, L Kontar, B. De Cagny, F. Brazier, D. Titeca, G. Bacari-Risal, J. Maizel, M. Amato, M. Slama P272 - Effect of recruitment maneuver on left ventricular systolic strain P. Mercado, J. Maizel, L. Kontar, D. Titeca, F. Brazier, A. Riviere, M. Joris, T. Soupison, B. De Cagny, S. El Dash, M. Slama P273 - Inhaled nitric oxide – is switching supplier cost effective? Remmington, A. Fischer, S. Squire, M. Boichat P274 - Epidemiological study of severe acute pancreatitis in Japan, comparison of the etiology and the patient outcomes on 1159 patients. H. Honzawa, H. Yasuda, T. Adati, S. Suzaki, M. Horibe, M. Sasaki, M. Sanui P275 - Extracorporeal liver support therapy. Experience in an intensive care unit R. Marinho, J. Daniel, H. Miranda, A. Marinho P276 - Accuracy of mortality prediction models in acute versus acute-on-chronic liver failure in the intensive care setting K. Milinis, M. Cooper, G. R. Williams, E. McCarron, S. Simants, I. Patanwala, I. Welters P277 - Risk of coronary artery disease in patients with chronic liver disease: a population based cohort study Y. Su P278 - 20 years of liver transplantation in Santiago de Compostela (Spain). Experience review J. Fernández Villanueva, R. Fernández Garda, A. López Lago, E. Rodríguez Ruíz, R. Hernández Vaquero, S. Tomé Martínez de Rituerto, E. Varo Pérez P279 - Diarrhea is a risk factor for liver injury and may lead to intestinal failure associated liver disease in critical illness N. Lefel, F. Schaap, D. Bergmans, S. Olde Damink, M. Van de Poll P280 - Bowel care on the intensive care unit: constipation guideline compliance and complications K. Tizard, C. Lister, L. Poole P281 - Malnutrition assessed by phase angle determines outcomes in low risk cardiac surgery patients D. Ringaitiene, D. Gineityte, V. Vicka, I. Norkiene, J. Sipylaite P282 - Preoperative fasting times in an irish hospital A. O’Loughlin, V. Maraj, J. Dowling P283 - Costs and final outcome of early x delayed feeding in a private Brazil ICU M. B. Velasco, D. M. Dalcomune, E. B. Dias, S. L. Fernandes P284 - Can ventilator derived energy expenditure measurements replace indirect calorimetry? T. Oshima, S. Graf, C. Heidegger, L. Genton, V. Karsegard, Y. Dupertuis, C. Pichard P285 - Revisiting the refeeding syndrome: results of a systematic review N. Friedli, Z. Stanga, B. Mueller, P. Schuetz P286 - Compliance with the new protocol for parenteral nutrition in our ICU L. Vandersteen, B. Stessel, S. Evers, A. Van Assche, L. Jamaer, J. Dubois P287 - Nutrition may be another treatment in the intensive care unit where less is more? R. Marinho, H. Castro, J. Moura, J. Valente, P. Martins, P. Casteloes, C. Magalhaes, S. Cabral, M. Santos, B. Oliveira, A. Salgueiro, A. Marinho P288 - Should we provide more protein to critically ill patients? R. Marinho, M. Santos, E. Lafuente, H. Castro, S. Cabral, J. Moura, P. Martins, B. Oliveira, A. Salgueiro, S. Duarte, S. Castro, M. Melo, P. Casteloes, A. Marinho P289 Protein provision in an adult intensive care unit S. Gray P290 - Prevalence and clinical outcomes of vitamin d deficiency in the medical critically ill patients in Songklanagarind hospital K. Maipang, R. Bhurayanontachai P291 - Vitamin d deficiency strongly predicts adverse medical outcome across different medical inpatient populations: results from a prospective study L. G. Grädel, P. Schütz P292 - Omega-3 fatty acids in patients undergoing cardiac surgery: a systematic review and meta-analysis P. Langlois, W. Manzanares P293 - Can 5-hydroxytriptophan prevent post-traumatic stress disorder in critically ill patients? R. Tincu, C. Cobilinschi, D. Tomescu, Z. Ghiorghiu, R. Macovei P294 - Parenteral selenium in the critically ill: an updated systematic review and meta-analysis W. Manzanares, P. Langlois, M. Lemieux, G. Elke, F. Bloos, K. Reinhart, D. Heyland P295 - Probiotics in the critically ill: an updated systematic review and meta-analysis P. Langlois, M. Lemieux, I. Aramendi, D. Heyland, W. Manzanares P296 - Diabetes with hyperglycemic crisis episodes may be associated with higher risk of pancreatic cancer: a population-based cohort study Y. Su P297 - Incidence of hypoglycemia in an intensive care unit depending on insulin protocol R. Marinho, N. Babo, A. Marinho P298 - Severity of the diseases is two-dimensionally correlated to blood glucose, including blood glucose variability, especially in moderately to severely ill patients with glucose intolerance. M. Hoshino, Y. Haraguchi, S. Kajiwara, T. Mitsuhashi, T. Tsubata, M. Aida P299 - A study of glycemic control by subcutaneous glargine injection transition from continuous regular insulin infusion in critically ill patients T. Rattanapraphat, R. Bhurayanontachai, C. Kongkamol, B. Khwannimit P300 - Glycemic control in Portuguese intensive care unit R. Marinho, M. Santos, H. Castro, E. Lafuente, A. Salgueiro, S. Cabral, P. Martins, J. Moura, B. Oliveira, M. Melo, B. Xavier, J. Valente, C. Magalhaes, P. Casteloes, A. Marinho P301 - Impact of hyperglycemia duration on the day of operation on short-term outcome of cardiac surgery patients D. Moisidou, F. Ampatzidou, C. Koutsogiannidis, M. Moschopoulou, G. Drossos P302 - Lactate levels in diabetic ketoacidosis patients at ICU admissions G. Taskin, M. Çakir, AK Güler, A. Taskin, N. Öcal, S. Özer, L. Yamanel P303 - Intensive care implications of merging heart attack centre units in London J. M. Wong, C. Fitton, S. Anwar, S. Stacey P304 - Special characteristics of in-hospital cardiac arrests M. Aggou, B. Fyntanidou, S. Patsatzakis, E. Oloktsidou, K. Lolakos, E. Papapostolou, V. Grosomanidis P305 - Clinical evaluation of ICU-admitted patients who were resuscitated in the general medicine ward S. Suda , T. Ikeda, S. Ono, T. Ueno, Y. Izutani P306 - Serious game evaluation of a one-hour training basic life support session for secondary school students: new tools for future bystanders S. Gaudry, V. Desailly, P. Pasquier, PB Brun, AT Tesnieres, JD Ricard, D. Dreyfuss, A. Mignon P307 - Public and clinical staff perceptions and knowledge of CPR compared to local and national data J. C White, A. Molokhia, A. Dean, A. Stilwell, G. Friedlaender P308 Dispatcher-assisted telephone cardiopulmonary resuscitation using a French-language compression-ventilation pediatric protocol M. Peters, S. Stipulante, A. Delfosse, AF Donneau, A. Ghuysen P309 Dantrolene versus amiodarone for resuscitation – an experimental study C. Feldmann, D. Freitag, W. Dersch, M. Irqsusi, D. Eschbach, T. Steinfeldt, H. Wulf, T. Wiesmann P310 Long term survival and functional neurological outcome in comatose survivors undergoing therapeutic hypothermia N. Kongpolprom, J. Cholkraisuwat P311 Impact of kidney disease on mortality and neurological outcome in out-of-hospital cardiac arrest: a prospective observational study S. Beitland , E. Nakstad, H. Stær-Jensen , T. Drægni , G. Andersen , D. Jacobsen , C. Brunborg, B. Waldum-Grevbo , K. Sunde P312 ICU dependency of patients admitted after primary percutaneous coronary intervention (PPCI) following out of the hospital cardiac arrest K. Hoyland, D. Pandit P313 Prognostic indicators and outcome prediction model for patients with return of spontaneous circulation from cardiopulmonary arrest: comprehensive registry of in-hospital intensive care on OHCA survival (critical) study in Osaka, Japan K. Hayakawa P314 Cerebral oxygen saturation during resuscitation in a porcine model of cardiac arrest E. Oloktsidou, K. Kotzampassi, B. Fyntanidou, S. Patsatzakis, L. Loukipoudi, E. Doumaki, V. Grosomanidis P315 Presumption of cardiopulmonary resuscitation for sustaining cerebral oxidation using regional cerebral saturation of oxygen: observational cohort study (press study) H. Yasuda P316 EEG reactivity in patients after cardiac arrest: a close look at stimuli MM Admiraal, M. Van Assen, MJ Van Putten, M. Tjepkema-Cloostermans, AF Van Rootselaar, J. Horn P317 Prognostic value of neuron-specific enolase after cardiac arrest F. Ragusa, A. Marudi , S. Baroni, A. Gaspari, E. Bertellini P318 Correlation between electroencephalographic findings and serum neuron specific enolase with outcome of post cardiac arrest patients A. Taha, T. Abdullah, S. Abdel Monem P319 Introduction of a targeted temperature management strategy following cardiac arrest in a district general hospital intensive care unit. S. Alcorn, S. McNeill, S. Russell P320 The evolution of cerebral oxygen saturation in post-cardiac arrest patients treated with therapeutic hypothermia W. Eertmans, C. Genbrugge, I. Meex, J. Dens, F. Jans, C. De Deyne P321 Prognostic factors and neurological outcomes of therapeutic hypothermia in comatose survivors from cardiac arrest: 8-year single center experience J. Cholkraisuwat, N. Kongpolprom P322 Adherence to targeted temperature management after out of hospital cardiac arrest B. Avard, R. Burns P323 Implementation of a therapeutic hypothermia protocol for comatose survivors of out-of-hospital cardiac arrest. A. Patarchi, T. Spina P324 Factors associated with ventilator weaning after targeted temperature management for cardiac arrest patients in japan H. Tanaka, N. Otani, S. Ode, S. Ishimatsu P325 Differential activation of c-fos in paraventricular nuclei of the hypothalamus and thalamus of the rat following myocardial infarction J. Cho, J. B. Moon, C. W. Park, T. G. Ohk, M. C. Shin, M. H. Won P326 Monitoring of cTroponin I in patients with acute ischemic stroke - predictor of inhospital mortality S. Dakova, Z. Ramsheva, K. Ramshev P327 Hyperthermic preconditioning severely accelerates neuronal damage in the gerbil ischemic hippocampal dentate gyrus via decreasing sods expressions J. Cho, J. B. Moon, C. W. Park, T. G. Ohk, M. C. Shin P328 Failure in neuroprotection of remote limb ischemic post conditioning in the hippocampus of a gerbil model of transient cerebral ischemia J. Cho, J. B. Moon, C. W. Park, T. G. Ohk, M. C. Shin P329 Brain death and admission diagnosis in neurologic intensive care unit, a correlation? A Marudi, S Baroni, A Gaspari, E Bertellini P330 Brain magnetic resonance imaging findings in patients with septic shock G. Orhun, E. Senturk, P. E. Ozcan, S. Sencer, C. Ulusoy, E. Tuzun, F . Esen P331 Benefits of L-carnitine in valproic acid induced encephalopathy R. Tincu, C. Cobilinschi, D. Tomescu, Z. Ghiorghiu, R. Macovei P332Automatic analysis of EEG reactivity in comatose patients M. Van Assen, M. M. Admiraal, M. J. Van Putten, M. Tjepkema-Cloostermans, A. F. Van Rootselaar, J. Horn P333 Usefulness of common ICU severity scoring systems in predicting outcome after spontaneous intracerebral hemorrhage M. Fallenius, M. B. Skrifvars, M. Reinikainen, S. Bendel, R. Raj P334 Evalution of patients with suspected subarachnoid haemorrhage and negative ct imaging M. Abu-Habsa, C. Hymers, A. Borowska, H. Sivadhas, S. Sahiba, S. Perkins P335 Timing of endovascular and surgical treatment for aneurysmal subarachnoid haemorrhage: early but not so fast. J. Rubio, J. A. Rubio, R. Sierra P336 Red blood cell transfusion in aneurysmal subarachnoid hemorrhage – the Sahara cohort study S. English, M. Chasse, A. Turgeon, F. Lauzier, D. Griesdale, A. Garland, D. Fergusson, R. Zarychanski, A. Tinmouth, C. Van Walraven, K. Montroy, J. Ziegler, R. Dupont Chouinard, R. Carignan, A. Dhaliwal, C. Lum, J. Sinclair, G. Pagliarello, L. McIntyre P337 - Aneurysmal subarachnoid hemorrhage and anemia: a canadian multi-centre retrospective cohort study S. English, M. Chasse, A. Turgeon, F. Lauzier, D. Griesdale, A. Garland, D. Fergusson, R. Zarychanski, A. Tinmouth, C. Van Walraven, K. Montroy, J. Ziegler, R. Dupont Chouinard, R. Carignan, A. Dhaliwal, C. Lum, J. Sinclair, G. Pagliarello, L. McIntyre P338 - Does the neutrophil-to-lymphocyte (NLR) ratio predict symptomatic vasospasm or delayed cerebral ischemia (DCI) after aneurysmal subarachnoid haemorrhage (SAH)? T. Groza, N. Moreau, D. Castanares-Zapatero, P. Hantson P339 - ICU-acquired infections in aneurysmal subarachnoid hemorrhage patients: impact on ICU and hospital length of stay M. Carbonara , F. Ortolano, T. Zoerle, S. Magnoni, S. Pifferi, V. Conte, N. Stocchetti P340 - Cerebral metabolic effects of normobaric hyperoxia during the acute phase of aneurysmal subarachnoid hemorrhage L. Carteron, T. Suys, C. Patet, H. Quintard, M. Oddo P341 - Postoperative care for elective craniotomy: where is best done? J. A. Rubio, J. Rubio, R. Sierra P342 - 5-year follow-up of patients after transplantation of organs from donors from neurocritical care V. Spatenkova, E. Pokorna, P. Suchomel P343 - Evaluation of levetiracetam pharmacokinetics after severe traumatic brain injury in neurocritical care patients at a level one trauma center N. Ebert, J. Jancik, H. Rhodes P344 - Model based time series cluster analysis to determine unique patient states in traumatic brain injury T. Bylinski, C. Hawthorne, M. Shaw, I. Piper, J. Kinsella P345 - Brain compartment monitoring capabilities from ICP to BI (bioimpedance) during HS (hypertonic saline) administration. State of art simulation outcome depending on brain swelling type A. K. Kink , I. R. Rätsep P346 - Transfusion of red blood cells in patients with traumatic brain injury admitted to Canadian trauma health centers: a multicenter cohort study A. Boutin, L. Moore, M. Chasse, R. Zarychanski, F. Lauzier, S. English, L. McIntyre, J. Lacroix, D. Griesdale, P. Lessard-Bonaventure, A. F. Turgeon P347 - Hemoglobin thresholds and red blood cell transfusions in adult patients with moderate or severe traumatic brain injury: a retrospective cohort study A. Boutin, L. Moore, R. Green, P. Lessard-Bonaventure, M. Erdogan, M. Butler, F. Lauzier, M. Chasse, S. English, L. McIntyre, R. Zarychanski, J. Lacroix, D. Griesdale, P. Desjardins, D. A. Fergusson, A. F. Turgeon P348 - Characteristics of patients with gunshot wounds to the head - an observational Brazilian study B. Goncalves, B. Vidal, C. Valdez, A. C. Rodrigues, L. Miguez, G. Moralez P349 - Base excess as predictor for ICU admission and the injury severity in blunt trauma patients T. Hong P350 - Enhancement of usual emergency department care with proadrenomedullin to improve outcome prediction - Results from the multi-national, prospective, observational TRIAGE study A. Kutz, P. Hausfater, D. Amin, T. Struja, S. Haubitz, A. Huber, B. Mueller, P. Schuetz P351 - Developing an innovative emergency medicine point-of-care simulation programme T. Brown, J. Collinson, C. Pritchett, T. Slade P352 - The InSim program: an in situ simulation program for junior trainees in intensive care M. Le Guen, S. Hellings, R. Ramsaran P353 - Impact of excessive and inappropriate troponin testing in the emergency setting how good are we A. Alsheikhly P354 - The development of time tracking monitor at emergency department T. Abe P355 - Role of focussed echocardiography in emergency assessment of syncope L. Kanapeckaite, M. Abu-Habsa, R. Bahl P356 - Insertion of an open-ended 14-gauge catheter through the chest wall causes a significant pneumothorax in a self-ventilating swine model M. Q Russell, K. J. Real, M. Abu-Habsa , R. M. Lyon, N. P. Oveland P357 - Ez-io® intraosseous access teaching in the workplace using a mobile ‘tea trolley’ training method J. Penketh, M. Mcdonald, F. Kelly P358 - Black widow envenomation in Saudi Arabia: a prospective observational case series M. Alfafi, S. Alsolamy, W. Almutairi, B. Alotaibi P359 - Mechanical ventilation in patients with overdose not yet intubated on icu admission A. E. Van den Berg, Y. Schriel, L. Dawson, I. A. Meynaar P360 - Central nervous system depressants poisoning and ventilator associated pneumonia: an underrated risk factor in toxicological intensive care unit H. Talaie P361 - Acute barium intoxication treated with hemodiafiltration D. Silva, S. Fernandes, J. Gouveia, J. Santos Silva P362 - Major trauma presenting to the emergency department. the spectrum of cycling injuries in Ireland J. Foley, A. Kaskovagheorgescu, D. Evoy, J. Cronin, J. Ryan P363 - Burns from French military operations: a 14-year retrospective observational analysis. M. Huck, C. Hoffmann, J. Renner, P. Laitselart, N. Donat, A. Cirodde, J. V. Schaal, Y. Masson, A. Nau, T. Leclerc P364 - A comparison of mortality scores in burns patients on the intensive care unit. O. Howarth, K. Davenport, P. Jeanrenaud, S. Raftery P365 - Clasification of pain and its treatment and an intensive care rehabiliation clinic P. MacTavish, H. Devine, J. McPeake, M. Daniel, J. Kinsella, T. Quasim P366 - Pain management adequacy in critical care areas ,the process and the barriers perceived by critical care nurses S. Alrabiee, A. Alrashid , S. Alsolamy P367 - Pain assessment in critically ill adult patients: validation of the Turkish version of the critical-care pain observation tool O. Gundogan, C. Bor, E. Akýn Korhan, K. Demirag , M. Uyar P368 - An audit of pain and sedation assessments in the intensive care unit: recommendations for clinical practice F. Frame, C. Ashton, L. Bergstrom Niska P369 - Impact of pharmaceutical care on treatment of pain and agitation in medical intensive care unit P. Dilokpattanamongkol, T. Suansanae, C. Suthisisang, S. Morakul, C. Karnjanarachata, V. Tangsujaritvijit P370 - Agitation in trauma ICU, prevention and outcome S. Mahmood, H. Al Thani, A. Almenyar P371 Correlation between percentages of ventilated patients developed vap and use of sedative agents in icu patients. A. Vakalos , V. Avramidis P372 - Improving recording of sedation events in the Emergency Department: The implementation of the SIVA International Taskforce adverse event reporting tool for procedural sedation R. Sharvill, J. Penketh P373 - Impact of sedative drug use on the length of mechanical ventilation S. E. Morton, Y. S. Chiew, C. Pretty, J. G. Chase, G. M. Shaw P374 - Co-administration of nitric oxide and sevoflurane using anaconda R. Knafelj, P. Kordis P375 - A retrospective study of the use of Dexmedetomidine in an oncological critical care setting S. Patel, V. Grover P376 - Dexmedetomidine and posttraumatic stress disorder incidence in alcohol withdrawal icu patients I. Kuchyn, K. Bielka P377 - Hemodynamic effects of dexmedetomidine in a porcine model of septic shock Z. Aidoni, V. Grosomanidis, K. Kotzampassi, G. Stavrou, B. Fyntanidou, S. Patsatzakis, C. Skourtis P378 - Ketamine for analgosedation in severe hypoxic respiratory failure S. D. Lee, K. Williams, I. D. Weltes P379 - Madness from the moon? lunar cycle and the incidence of delirium on the intensive care unit S. Berhane, C. Arrowsmith, C. Peters, S. Robert P380 - Impaired dynamic cerebral autoregulation after coronary artery bypass grafting and association with postoperative delirium J. Caldas, R. B. Panerai, T. G. Robinson, L. Camara, G. Ferreira, E. Borg-Seng-Shu, M. De Lima Oliveira, N. C. Mian, L. Santos, R. Nogueira, S. P. Zeferino, M. Jacobsen Teixeira, F. Galas, L. A. Hajjar P381 - Risk factors predicting prolonged intensive care unit length of stay after major elective surgery. P. Killeen, M. McPhail, W. Bernal, J. Maggs, J. Wendon, T. Hughes P382 - Systemic inflammatory response syndrome criteria and hospital mortality prediction in a brazilian cohort of critically ill patients L. U. Taniguchi, E. M. Siqueira, J. M. Vieira Jr, L. C. Azevedo P383 - Evaluating the efficacy of a risk predictor panel in identifying patients at elevated risk of morbidity following emergency admission A. N. Ahmad, M. Abu-Habsa, R. Bahl, E. Helme, S. Hadfield, R. Loveridge P384 - A retrospective comparison of outcomes for elective surgical patients admitted post-operatively to the critical care unit or general ward J. Shak, C. Senver, R. Howard-Griffin P385 - Effect of obesity on mortality in surgical critically ill patients. P. Wacharasint, P. Fuengfoo, N. Sukcharoen, R. Rangsin P386 - The national early warning score (news) reliably improves adverse clinical outcome prediction in community-acquired pneumonia - results from a 6 year follow-up D. Sbiti-Rohr, P. Schuetz P387 - Clinical usefulness of the charlson¡¯s weighted index of comorbidities _as prognostic factor in patients with prolonged acute mechanical ventilation H. Na, S. Song, S. Lee, E. Jeong, K. Lee P388 - Comparison of mortality prediction scoring systems in patients with cirrhosis admitted to general intensive care unit M. Cooper, K. Milinis, G. Williams, E. McCarron, S. Simants, I. Patanwala, I. D. Welters P389 - Impact of admission source and time of admission on outcome of pediatric intensive care patients: retrospective 15 years study E. Zoumpelouli, EA Volakli, V. Chrysohoidou, S. Georgiou, K. Charisopoulou, E. Kotzapanagiotou, V. Panagiotidou, K. Manavidou, Z. Stathi, M. Sdougka P390 - Heart rate variability and outcomes prediction in critical illness N. Salahuddin, B. AlGhamdi, Q. Marashly, K. Zaza, M. Sharshir, M. Khurshid, Z. Ali, M. Malgapo, M. Jamil, A. Shafquat, M. Shoukri, M. Hijazi P391 - The incidence and outcome of hyperlactatemia in the post anaesthesia care unit T. Abe, S. Uchino, M. Takinami P392 - Correlation between arterial blood gas disturbances and arterial lactate levels during hospitalization and outcome in critically septic patients N. R. Rangel Neto, S. Oliveira, F. Q. Reis, F. A. Rocha P393 - External validation of saps 3 and mpm iii scores in 48,816 patients from 72 brazilian icus G. Moralez, K. Ebecken, L. S. Rabello, M. F. Lima, R. Hatum, F. V. De Marco, A. Alves, J. E. Pinto, M. Godoy, P. E. Brasil, F. A. Bozza, J. I. Salluh, M. Soares P394 - The frailty penalty: pre-admission functional status confounds mortality prediction models in critically ill patients J. Krinsley, G. Kang P395 - ‘sooner rather than later”: how delayed discharge from critical care leads to increased out of hours discharges and subsequent increase in in-hospital mortality. J. Perry, H. Hines P396 - Identifying poor outcome patient groups in a resource-constrained critical care unit K. M. Wilkinson, C. Tordoff, B. Sloan, M. C. Bellamy P397 - Effects of icu weekend admission and discharge on mortality. E. Moreira, F. Verga, M. Barbato, G. Burghi P398 - Organizational factors, outcomes and resource use in 9,946 cancer patients admitted to 70 ICUs M Soares, U. V. Silva, L. C. Azevedo, A. P. Torelly, J. M. Kahn, D. C. Angus, M. F. Knibel, P. E. Brasil, F. A. Bozza, J. I. Salluh P399 - Evaluation of oncological critically ill patients, severity score and outcome compared to not oncological in a particular hospital cti. M. B. Velasco, D. M. Dalcomune P400 - Outcomes of patients admitted to a large uk critical care department with palliative oncological diagnoses R. Marshall, T. Gilpin, A. Tridente, A. Raithatha P401 - Predictors of mortality in febrile neutropenic patients with haematological malignancies admitted to an intensive care unit of a cancer center D. Mota, B. Loureiro, J. Dias, O. Afonso, F. Coelho, A. Martins, F. Faria P402 - Patients with hematologic malignancies requiring invasive mechanical ventilation: characteristics and predictors of mortality H. Al-Dorzi, H. Al Orainni , F. AlEid, H. Tlaygeh, A. Itani, A. Hejazi, Y. Arabi P403 - Patient-important outcomes in randomized controlled trials in critically ill patients: a systematic review S. Gaudry, J. Messika, J. D. Ricard, S. Guillo, B. Pasquet, E. Dubief, D. Dreyfuss, F. Tubach P404 - Alopecia in survivors of critical illness: a qualitative study C . Battle, K. James, P. Temblett P405 - The impact of mental health on icu admission L. Davies, C. Battle, C. Lynch P406 - Cognitive impairment 5 years after ICU discharge S. Pereira, S. Cavaco, J. Fernandes, I. Moreira, E. Almeida, F. Seabra Pereira, M. Malheiro, F. Cardoso, I. Aragão, T. Cardoso P407 - Apache ii versus apache iv for octagenerians in medical icu M. Fister, R. Knafelj P408 - Outcomes of octagenarians in an indian icu P. Muraray Govind, N. Brahmananda Reddy, R. Pratheema, E. D. Arul, J. Devachandran P409 - Mortality and outcomes in elderly patients 80 years of age or older admitted to the icu M. B. Velasco , D. M. Dalcomune P410 - Octagenerians in medical icu - adding days to life or life to days? R. Knafelj, M. Fister P411 - The very elderly admitted to intensive care unit: outcomes and economic evaluation N. Chin-Yee, G. D’Egidio, K. Thavorn, D. Heyland, K. Kyeremanteng P412 - The very elderly in intensive care: relationship between acuity of illness and long-term mortality A. G. Murchison, K. Swalwell, J. Mandeville, D. Stott P413 - Acquired weakness in an oncological intensive care unit I. Guerreiro P414 - Musculoskeletal problems in intensive care unit (ICU) patients post-discharge H. Devine, P. MacTavish, J. McPeake, T. Quasim, J. Kinsella, M. Daniel P415 - Premorbid obesity, but not nutrition, prevents critical illness-induced muscle wasting and weakness C. Goossens M. B. Marques, S. Derde, S. Vander Perre, T. Dufour, S. E. Thiessen, F. Güiza, T. Janssens, G. Hermans, I. Vanhorebeek, K. De Bock, G. Van den Berghe, L. Langouche P416 - Physical outcome measures for critical care patients following intensive care unit (icu) discharge H. Devine, P. MacTavish, T. Quasim, J. Kinsella, M. Daniel, J. McPeake P417 - Improving active mobilisation in a general intensive care unit B. Miles , S. Madden, H. Devine P418 - Mobilization in patients on vasoactive drugs use – a pilot study. M. Weiler, P. Marques, C. Rodrigues, M. Boeira, K. Brenner, C. Leães, A. Machado, R. Townsend, J. Andrade P419 - Pharmacy intervention at an intensive care rehabilitation clinic P. MacTavish, J. McPeake, H. Devine, J. Kinsella, M. Daniel, R. Kishore, C. Fenlon, T. Quasim P420 - Interactive gaming is feasible and potentially increases icu patients’ motivation to be engaged in rehabilitation programs T. Fiks, A. Ruijter, M. Te Raa, P. Spronk P421 - Simulation-based design of a robust stopping rule to ensure patient safety Y. S. Chiew, P. Docherty, J. Dickson, E. Moltchanova, C. Scarrot, C. Pretty, G. M. Shaw, J. G. Chase P422 - Are daily blood tests on the intensive care unit necessary? T. Hall, W. C. Ngu, J. M. Jack, P. Morgan P423 - Measuring urine output in ward patients: is it helpful? B. Avard, A. Pavli, X. Gee P424 - The incidence of pressure ulcers in an adult mixed intensive care unit in turkey C . Bor, E. Akin Korhan, K. Demirag, M. Uyar P425 - Intensivist/patient ratios in closed ICUs in Alexandria, Egypt; an overview M. Shirazy, A. Fayed P426 - Eicu (electronic intensive care unit): impact on ALOS (average length of stay) in a developing country like India S. Gupta, A. Kaushal, S. Dewan, A. Varma P427 - Predicting deterioration in general ward using early deterioration indicator E. Ghosh, L. Yang, L. Eshelman, B. Lord, E. Carlson P428 - High impact enhanced critical care outreach - the imobile service: making a difference E. Helme, R. Broderick, S. Hadfield, R. Loveridge P429 - Impact of bed availability and cognitive load on intensive care unit (ICU) bed allocation: a vignette-based trial J. Ramos, D. Forte P430 - Characteristics of critically ill patients admitted through the emergency department F. Yang, P. Hou P431 - Admission to critical care: the quantification of functional reserve J. Dudziak, J. Feeney, K. Wilkinson, K. Bauchmuller, K. Shuker, M. Faulds, A. Raithatha, D. Bryden, L. England, N. Bolton, A. Tridente P432 - Admission to critical care: the importance of frailty K. Bauchmuller, K Shuker, A Tridente, M Faulds, A Matheson, J. Gaynor, D Bryden, S South Yorkshire Hospitals Research Collaboration P433 - Development of an instrument to aid triage decisions for intensive care unit admission J. Ramos, B. Peroni, R. Daglius-Dias, L. Miranda, C. Cohen, C. Carvalho, I . Velasco, D. Forte P434 - Using selective serotonin re-uptake inhibitors and serotonin-norepinephrine re-uptake inhibitors in critical care: a systematic review of the evidence for benefit or harm J. M. Kelly, A. Neill, G. Rubenfeld, N. Masson, A. Min P435 - Measuring adaptive coping of hospitalized patients with a severe medical condition:the sickness insight in coping questionnaire (sicq) E. Boezeman, J. Hofhuis , A. Hovingh, R. De Vries, P. Spronk P436 - Results of a national survey regarding intensive care medicine training G. Cabral-Campello, I. Aragão, T. Cardoso P437 - Work engagement among healthcare professionals in the intensive care unit M. Van Mol, M. Nijkamp, E . Kompanje P438 - Empowering the intensive care practitioners. is it a burnout ameliorating intervention? P. Ostrowski, A. Omar P439 - Icu patients suffer from circadian rhythm desynchronisation K. Kiss , B. Köves, V. Csernus, Z. Molnár P440 - Noise reduction in the ICU: feasible ? Y. Hoydonckx, S. Vanwing, B. Stessel, A. Van Assche, L. Jamaer, J. Dubois P441 - Accidental removal of invasive devices in the critical patient into the bed-washing. does the presence of professional nurse modify his incidence? V. Medo, R. Galvez, J. P. Miranda P442 - Deprivation of liberty safeguards (dols): audit of compliance in a of a 16-bed specialist cancer critical care unit. C. Stone, T. Wigmore P443 - Use of a modified cristal score to predict futility of critical care in the elderly Y. Arunan, A. Wheeler, K. Bauchmuller, D. Bryden P444 - Improvement of Referral Rate to Palliative Care for Patients with Poor Prognosis in Neurosurgical Intensive Care Unit Y. Wong, C. Poi, C. Gu P445 - Factors associated with limitation of life supporting care (lsc) in a medico-surgical intermediate care unit, and outcome of patients with lsc limitation: a monocentric, six-month study. P. Molmy, N. Van Grunderbeeck, O. Nigeon, M. Lemyze, D. Thevenin, J. Mallat P446 - Palliative care consultation and intensive care unit admission request: a cohort study J. Ramos, M. Correa, R. T. Carvalho, D. Forte P447 - Nursing and medicine together in postsurgical intensive care unit: situations of prognostic conflict at the end of life. our critical care nurses suffer with our medical activism? A. Fernandez, C. McBride P448 - End of life who may decide E. Koonthalloor, C. Walsh P449 - Correctly diagnosing death A. Webber, M. Ashe, K. Smith, P. Jeanrenaud P450 - Skin procurement performed by intensive care physicians: yes, we can. A. Marudi , S. Baroni, F. Ragusa, E. Bertellini P451 - Death analysis in pediatric intensive care patients E. A. Volakli , E. Chochliourou, M. Dimitriadou, A. Violaki, P. Mantzafleri, E. Samkinidou, O. Vrani, A. Arbouti, T. Varsami, M. Sdougka P452 - The potential impact of euthanasia on organ donation: analysis of data from belgium J. A. Bollen, T. C. Van Smaalen, W. C. De Jongh, M. M. Ten Hoopen, D. Ysebaert, L. W. Van Heurn, W. N. Van Mook P453 - Communication within an intensive care setting K. Sim, A. Fuller P454 - Development and implementation of a longitudinal communication curriculum for critical care medicine fellows A. Roze des Ordons, P. Couillard, C. Doig P455 - Staff-family conflict in a multi-ethnic intensive care unit R. V. Van Keer, R. D. Deschepper, A. F. Francke, L. H. Huyghens, J. B. Bilsen P456 - Does the source of admission to critical care affect family satisfaction? B. Nyamaizi, C. Dalrymple, A. Molokhia, A. Dobru P457 - A simple alternative to the family satisfaction survey (fs-icu) E. Marrinan, A. Ankuli, A. Molokhia P458 - A study to explore the experiences of patient and family volunteers in a critical care environment: a phenomenological analysis J. McPeake, R. Struthers, R. Crawford , H. Devine , P. Mactavish , T. Quasim P459 - Prevalence and risk factors of anxiety and depression in relatives of burn patients. P. Morelli, M. Degiovanangelo, F. Lemos, V. MArtinez, F. Verga, J. Cabrera, G. Burghi P460 - Guidance of visiting children at an adult intensive care unit (icu) A. Rutten , S. Van Ieperen, S. De Geer, M. Van Vugt, E. Der Kinderen P461 - Visiting policies in Italian pediatric ICUs: an update A. Giannini, G Miccinesi, T Marchesi, E Prandi

Published
2016

10. Improving outcomes of severe infections by multidrug-resistant pathogens with polyclonal IgM-enriched immunoglobulins

Author

Giamarellos-Bourboulis, E.J. Tziolos, N. Routsi, C. Katsenos, C. Tsangaris, I. Pneumatikos, I. Vlachogiannis, G. Theodorou, V. Prekates, A. Antypa, E. Koulouras, V. Kapravelos, N. Gogos, C. Antoniadou, E. Mandragos, K. Armaganidis, A. Hellenic Sepsis Study Group

Abstract

The emergence of infections by multidrug-resistant (MDR) Gram-negative bacteria, which is accompanied by considerable mortality due to inappropriate therapy, led to the investigation of whether adjunctive treatment with one polyclonal IgM-enriched immunoglobulin preparation (IgGAM) would improve outcomes. One hundred patients in Greece with microbiologically confirmed severe infections by MDR Gram-negative bacteria acquired after admission to the Intensive Care Unit and treated with IgGAM were retrospectively analysed from a large prospective multicentre cohort. A similar number of patient comparators well-matched for stage of sepsis, source of infection, appropriateness of antimicrobials and co-morbidities coming from the same cohort were selected. All-cause 28-day mortality was the primary end point; mortality by extensively drug-resistant (XDR) pathogens and time to breakthrough bacteraemia were the secondary end points. Fifty-eight of the comparators and 39 of the IgGAM-treated cases died by day 28 (p 0.011). The OR for death under IgGAM treatment was 0.46 (95% CI 0.26–0.85). Stepwise regression analysis revealed that IgGAM was associated with favourable outcome whereas acute coagulopathy, cardiovascular failure, chronic obstructive pulmonary disease and chronic renal disease were associated with unfavourable outcome. Thirty-nine of 62 comparators (62.9%) were infected by XDR Gram-negative bacteria and died by day 28 compared with 25 of 65 cases treated with IgGAM (38.5%) (p 0.008). Median times to breakthrough bacteraemia were 4 days and 10 days, respectively (p

Published
2016

11. Clinical and pre-clinical biomarkers of Regorafenib (REG) efficacy in metastatic colorectal cancer (mCRC) in a phase II trial

Author

Khan, K., primary, Cunningham, D., additional, Vlachogiannis, G., additional, Hedayat, S., additional, Rata, M., additional, Koh, D-M., additional, Tunariu, N., additional, Jamin, Y., additional, Collins, D., additional, Chau, I., additional, Rao, S., additional, Watkins, D., additional, Starling, N., additional, Peckitt, C., additional, Fotiadis, N., additional, Saffery, C., additional, Hahne, J., additional, Fassan, M., additional, Braconi, C., additional, and Valeri, N., additional

Published
2017
Full Text
View/download PDF

13. KRAS mutations in circulating tumour DNA (ctDNA) in MRI-defined, high-risk, locally-advanced rectal cancer (LARC) patients (pts) from the EXPERT-C trial

Author

Sclafani, F., Chau, I., Cunningham, D., Vlachogiannis, G., Eltahir, Z., Lampis, A., Braconi, C., Kalaitzaki, E., De Castro, D. Gonzalez, Wotherspoon, A., Capdevila, J., Glimelius, Bengt, Cervantes, A., Begum, R., Lote, H., Mentrasti, G., Hahne, J. C., Tait, D., Brown, G., Valeri, N., Sclafani, F., Chau, I., Cunningham, D., Vlachogiannis, G., Eltahir, Z., Lampis, A., Braconi, C., Kalaitzaki, E., De Castro, D. Gonzalez, Wotherspoon, A., Capdevila, J., Glimelius, Bengt, Cervantes, A., Begum, R., Lote, H., Mentrasti, G., Hahne, J. C., Tait, D., Brown, G., and Valeri, N.

Published
2016
Full Text
View/download PDF

14. KRAS mutations in circulating tumour DNA (ctDNA) in MRI-defined, high-risk, locally-advanced rectal cancer (LARC) patients (pts) from the EXPERT-C trial

Author

Sclafani, F., primary, Chau, I., additional, Cunningham, D., additional, Vlachogiannis, G., additional, Eltahir, Z., additional, Lampis, A., additional, Braconi, C., additional, Kalaitzaki, E., additional, De Castro, D. Gonzalez, additional, Wotherspoon, A., additional, Capdevila, J., additional, Glimelius, B., additional, Cervantes, A., additional, Begum, R., additional, Lote, H., additional, Mentrasti, G., additional, Hahne, J.C., additional, Tait, D., additional, Brown, G., additional, and Valeri, N., additional

Published
2016
Full Text
View/download PDF

19. 37th International Symposium on Intensive Care and Emergency Medicine (part 3 of 3)

Author

Von Seth, M., Hillered, L., Otterbeck, A., Hanslin, K., Larsson, A., Sjölin, J., Lipcsey, M., Cove, ME, Chew, N. S., Vu, L. H., Lim, R. Z., Puthucheary, Z., Wilske, F., Skorup, P., Tano, E., Derese, I., Thiessen, S., Derde, S., Dufour, T., Pauwels, L., Bekhuis, Y., Van den Berghe, G., Vanhorebeek, I., Khan, M., Dwivedi, D., Zhou, J., Prat, A., Seidah, N. G., Liaw, P. C., Fox-Robichaud, A. E., Correa, T., Pereira, J, Takala, J, Jakob, S, Maudsdotter, L., Castegren, M., Sjölin, J, Xue, M., Xu, J. Y., Liu, L., Huang, Y. Z., Guo, F. M., Yang, Y., Qiu, H. B., Kuzovlev, A., Moroz, V., Goloubev, A., Myazin, A., Chumachenko, A., Pisarev, V., Takeyama, N., Tsuda, M., Kanou, H., Aoki, R., Kajita, Y., Hashiba, M., Terashima, T., Tomino, A., Davies, R., O’Dea, K. P., Soni, S., Ward, J. K., O’Callaghan, D. J., Takata, M., Gordon, A. C., Wilson, J., Zhao, Y., Singer, M., Spencer, J., Shankar-Hari, M., Genga, K. Roveran, Lo, C., Cirstea, M. S., Walley, K. R., Russell, J. A., Linder, A., Boyd, J. H., Sedlag, A., Riedel, C., Georgieff, M., Barth, E., Bracht, H., Essig, A., Henne-Bruns, D., Gebhard, F., Orend, K., Halatsch, M., Weiss, M., Chase, M., Freinkman, E., Uber, A., Liu, X., Cocchi, M. N., Donnino, M. W., Peetermans, M., Liesenborghs, L., Claes, J., Vanassche, T., Hoylaerts, M., Jacquemin, M., Vanhoorelbeke, K., De Meyer, S., Verhamme, P., Vögeli, A., Ottiger, M., Meier, M., Steuer, C., Bernasconi, L., Huber, A., Christ-Crain, M., Henzen, C., Hoess, C., Thomann, R., Zimmerli, W., Müller, B., Schütz, P., Hoppensteadt, D., Walborn, A., Rondina, M., Tsuruta, K., Fareed, J., Tachyla, S., Ikeda, T., Ono, S., Ueno, T., Suda, S., Nagura, T., Damiani, E., Domizi, R., Scorcella, C., Tondi, S., Pierantozzi, S., Ciucani, S., Mininno, N., Adrario, E., Pelaia, P., Donati, A., Andersen, M. Schou, Lu, S., Lopez, G, Lassen, AT, Ghiran, I., Shapiro, N. I., Trahtemberg, U., Sviri, S., Beil, M., Agur, Z., Van Heerden, P., Jahaj, E., Vassiliou, A., Mastora, Z., Orfanos, S. E., Kotanidou, A., Wirz, Y., Sager, R., Amin, D., Amin, A., Haubitz, S., Hausfater, P., Kutz, A., Mueller, B., Schuetz, P., Sager, R. S., Wirz, Y. W., Amin, D. A., Amin, A. A., Hausfater, P. H., Huber, A. H., Mueller, B, Schuetz, P, Gottin, L., Dell’amore, C., Stringari, G., Cogo, G., Ceolagraziadei, M., Sommavilla, M., Soldani, F., Polati, E., Baumgartner, T., Zurauskaité, G., Gupta, S., Devendra, A., Mandaci, D., Eren, G., Ozturk, F., Emir, N., Hergunsel, O., Azaiez, S., Khedher, S., Maaoui, A., Salem, M., Chernevskaya, E., Beloborodova, N., Bedova, A., Sarshor, Y. U., Pautova, A., Gusarov, V., Öveges, N., László, I., Forgács, M., Kiss, T., Hankovszky, P., Palágyi, P., Bebes, A., Gubán, B., Földesi, I., Araczki, Á., Telkes, M., Ondrik, Z., Helyes, Z., Kemény, Á., Molnár, Z., Spanuth, E., Ebelt, H., Ivandic, B., Thomae, R., Werdan, K., El-Shafie, M., Taema, K., El-Hallag, M., Kandeel, A., Tayeh, O., Eldesouky, M., Omara, A., Winkler, M. S., Holzmann, M., Nierhaus, A., Mudersbach, E., Schwedhelm, E., Daum, G., Kluge, S., Zoellner, C., Greiwe, G., Sawari, H., Kubitz, J., Jung, R., Reichenspurner, H., Groznik, M., Ihan, A., Andersen, L. W., Holmberg, M. J., Wulff, A., Balci, C., Haliloglu, M., Bilgili, B., Bilgin, H., Kasapoglu, U., Sayan, I., Süzer, M., Mulazımoglu, L., Cinel, I., Patel, V., Shah, S., Parulekar, P., Minton, C., Patel, J., Ejimofo, C., Choi, H., Costa, R., Caruso, P., Nassar, P., Fu, J., Jin, J., Xu, Y., Kong, J., Wu, D., Yaguchi, A., Klonis, A., Ganguly, S., Kollef, M., Burnham, C., Fuller, B., Mavrommati, A., Chatzilia, D., Salla, E., Papadaki, E., Kamariotis, S., Christodoulatos, S., Stylianakis, A., Alamanos, G., Simoes, M., Trigo, E., Silva, N., Martins, P., Pimentel, J., Baily, D., Curran, L. A., Ahmadnia, E., Patel, B. V., Adukauskiene, D., Cyziute, J, Adukauskaite, A., Pentiokiniene, D., Righetti, F., Colombaroli, E., Castellano, G., Man, M., Shum, H. P., Chan, Y. H., Chan, K. C., Yan, W. W., Lee, R. A., Lau, S. K., Dilokpattanamongkol, P., Thirapakpoomanunt, P., Anakkamaetee, R., Montakantikul, P., Tangsujaritvijit, V., Sinha, S., Pati, J., Sahu, S., Valanciene, D., Dambrauskiene, A., Hernandez, K., Lopez, T., Saca, D., Bello, M., Mahmood, W., Hamed, K., Al Badi, N., AlThawadi, S., Al Hosaini, S., Salahuddin, N., Cilloniz, C. C., Ceccato, A. C., Bassi, G. L. Li, Ferrer, M. F., Gabarrus, A. G., Ranzani, O. R., Jose, A. S. San, Vidal, C. G. Garcia, de la Bella Casa, J. P. Puig, Blasi, F. B., Torres, AT, Ciginskiene, A., Simoliuniene, R., Giuliano, G., Triunfio, D., Sozio, E., Taddei, E., Brogi, E., Sbrana, F., Ripoli, A., Bertolino, G., Tascini, C., Forfori, F., Fleischmann, C., Goldfarb, D., Schlattmann, P., Schlapbach, L., Kissoon, N., Baykara, N., Akalin, H., Arslantas, M. Kemal, Gavrilovic, S. G., Vukoja, M. V., Hache, M. H., Kashyap, R. K., Dong, Y. D., Gajic, O. G., Ranzani, O., Harrison, D., Rabello, L., Rowan, K., Salluh, J., Soares, M., Markota, A. M., Fluher, J. F., Kogler, D. K., Borovšak, Z. B., Sinkovic, A. S., Siddiqui, Z, Aggarwal, P., Iqbal, O., Lewis, M., Wasmund, R., Abro, S., Raghuvir, S., Barie, P. S., Fineberg, D., Radford, A., Casazza, A., Vilardo, A., Bellazzi, E., Boschi, R., Ciprandi, D., Gigliuto, C., Preda, R., Vanzino, R., Vetere, M., Carnevale, L., Kyriazopoulou, E., Pistiki, A., Routsi, C., Tsangaris, I., Giamarellos-Bourboulis, E., Pnevmatikos, I., Vlachogiannis, G., Antoniadou, E., Mandragos, K., Armaganidis, A., Allan, P., Oehmen, R., Luo, J., Ellis, C., Latham, P., Newman, J., Pritchett, C., Pandya, D., Cripps, A., Harris, S., Jadav, M., Langford, R., Ko, B., Park, H., Beumer, C. M., Koch, R., Beuningen, D. V., Oudelashof, A. M., Vd Veerdonk, F. L., Kolwijck, E., VanderHoeven, J. G., Bergmans, D. C., Hoedemaekers, C., Brandt, J. B., Golej, J., Burda, G., Mostafa, G., Schneider, A., Vargha, R., Hermon, M., Levin, P., Broyer, C, Assous, M., Wiener-Well, Y., Dahan, M., Benenson, S., Ben-Chetrit, E, Faux, A., Sherazi, R., Sethi, A., Saha, S., Kiselevskiy, M., Gromova, E., Loginov, S., Tchikileva, I., Dolzhikova, Y., Krotenko, N., Vlasenko, R., Anisimova, N., Spadaro, S., Fogagnolo, A., Remelli, F., Alvisi, V., Romanello, A., Marangoni, E., Volta, C., Degrassi, A., Mearelli, F., Casarsa, C., Fiotti, N., Biolo, G., Cariqueo, M., Luengo, C., Galvez, R., Romero, C., Cornejo, R., Llanos, O., Estuardo, N., Alarcon, P., Magazi, B., Khan, S., Pasipanodya, J., Eriksson, M., Strandberg, G., Lipsey, M., Rajput, Z., Hiscock, F., Karadag, T., Uwagwu, J., Jain, S., Molokhia, A., Barrasa, H., Soraluce, A., Uson, E., Rodriguez, A., Isla, A., Martin, A., Fernández, B., Fonseca, F., Sánchez-Izquierdo, J. A., Maynar, F. J., Kaffarnik, M., Alraish, R., Frey, O., Roehr, A., Stockmann, M., Wicha, S., Shortridge, D., Castanheira, M., Sader, H. S., Streit, J. M., Flamm, R. K., Falsetta, K., Lam, T., Reidt, S., Jancik, J., Kinoshita, T., Yoshimura, J., Yamakawa, K., Fujimi, S., Torres, A., Zakynthinos, S., Mandragos, C., Ramirez, P., De la Torre-Prados, M., Dale, G., Wach, A., Beni, L., Hooftman, L., Zwingelstein, C., François, B., Colin, G., Dequin, P. F., Laterre, P. F., Perez, A., Welte, R., Lorenz, I., Eller, P., Joannidis, M., Bellmann, R., Lim, S., Chana, S., Patel, S., Higuera, J., Cabestrero, D., Rey, L., Narváez, G., Blandino, A., Aroca, M., Saéz, S., De Pablo, R, Albert, C. Nadège, Langouche, L., Goossens, C., Peersman, N., Vermeersch, P., Vander Perre, S., Holst, J., Wouters, P., Uber, A. U., Holmberg, M., Konanki, V., McNaughton, M., Zhang, J., Demirkiran, O., Byelyalov, A., Guerrero, J., Cariqueo, M, Rossini, N., Falanga, U., Monaldi, V., Cole, O., Scawn, N., Balciunas, M., Blascovics, I., Vuylsteke, A., Salaunkey, K., Omar, A., Salama, A., Allam, M., Alkhulaifi, A., Verstraete, S., Van Puffelen, E., Ingels, C., Verbruggen, S., Joosten, K., Hanot, J., Guerra, G., Vlasselaers, D., Lin, J., Haines, R., Zolfaghari, P., Hewson, R., Offiah, C., Prowle, J., Buter, H., Veenstra, J. A., Koopmans, M., Boerma, E. C., Taha, A., Shafie, A., Hallaj, S., Gharaibeh, D., Hon, H., Bizrane, M., El Khattate, A. A., Madani, N., Abouqal, R., Belayachi, J., Kongpolprom, N., Sanguanwong, N., Sanaie, S., Mahmoodpoor, A., Hamishehkar, H., Biderman, P., Avitzur, Y., Solomon, S., Iakobishvili, Z., Carmi, U., Gorfil, D, Singer, P., Paisley, C., Patrick-Heselton, J., Mogk, M., Humphreys, J., Welters, I., Casarotta, E., Bolognini, S., Moskowitz, A., Patel, P., Grossestreuer, A., Malinverni, S., Goedeme, D., Mols, P., Langlois, P. L., Szwec, C., D’Aragon, F., Heyland, D. K., Manzanares, W., Langlois, P., Aramendi, I., Heyland, D., Stankovic, N., Nadler, J., Sanchez, L., Wolfe, R., Donnino, M., Cocchi, M., Atalan, H. K., Gucyetmez, B., Kavlak, M. E., Aslan, S., Kargi, A., Yazici, S., Donmez, R., Polat, K. Y., Piechota, M, Piechota, A., Misztal, M., Bernas, S., Pietraszek-Grzywaczewska, I., Saleh, M., Hamdy, A., Elhallag, M., Atar, F., Kundakci, A., Gedik, E., Sahinturk, H., Zeyneloglu, P., Pirat, A., Popescu, M., Tomescu, D., Van Gassel, R., Baggerman, M., Schaap, F., Bol, M., Nicolaes, G., Beurskens, D., Damink, S. Olde, Van de Poll, M., Horibe, M., Sasaki, M., Sanui, M., Iwasaki, E., Sawano, H., Goto, T., Ikeura, T., Hamada, T., Oda, T., Mayumi, T., Kanai, T., Kjøsen, G., Horneland, R., Rydenfelt, K., Aandahl, E., Tønnessen, T., Haugaa, H., Lockett, P., Evans, L., Somerset, L., Ker-Reid, F., Laver, S., Courtney, E., Dalton, S., Georgiou, A., Robinson, K., Haas, B., Bartlett, K., Bigwood, M., Hanley, R., Morgan, P., Marouli, D., Chatzimichali, A., Kolyvaki, S., Panteli, A., Diamantaki, E., Pediaditis, E., Sirogianni, P., Ginos, P., Kondili, E., Georgopoulos, D., Askitopoulou, H., Zampieri, F. G., Liborio, A. B., Besen, B. A., Cavalcanti, A. B., Dominedò, C., Dell’Anna, A. M., Monayer, A., Grieco, D. L., Barelli, R., Cutuli, S. L., Maddalena, A. Ionescu, Picconi, E., Sonnino, C., Sandroni, C., Antonelli, M., Tuzuner, F., Cakar, N., Jacob, M., Sahu, S, Singh, Y. P., Mehta, Y., Yang, K. Y., Kuo, S., Rai, V., Cheng, T., Ertmer, C., Czempik, P, Hutchings, S., Watts, S., Wilson, C., Burton, C., Kirkman, E., Drennan, D., O’Prey, A., MacKay, A., Forrest, R., Oglinda, A., Ciobanu, G., Casian, M., Oglinda, C., Lun, C. T., Yuen, H. J., Ng, G., Leung, A., So, S. O., Chan, H. S., Lai, K. Y., Sanguanwit, P., Charoensuk, W., Phakdeekitcharoen, B., Batres-Baires, G., Kammerzell, I., Lahmer, T., Mayr, U., Schmid, R., Huber, W., Bomberg, H., Klingele, M., Groesdonk, H., Piechota, M., Mirkiewicz, K., Pérez, A. González, Silva, J., Ramos, A., Acharta, F., Perezlindo, M., Lovesio, L., Antonelli, P. Gauna, Dogliotti, A., Lovesio, C., Baron, J., Schiefer, J., Baron, D. M., Faybik, P., Chan, T. M., Ginos, P, Vicka, V., Gineityte, D., Ringaitiene, D., Sipylaite, J., Pekarskiene, J., Beurskens, D. M., Van Smaalen, T. C., Hoogland, P., Winkens, B., Christiaans, M. H., Reutelingsperger, C. P., Van Heurn, E., Nicolaes, G. A., Schmitt, F. S., Salgado, E. S., Friebe, J. F., Fleming, T. F., Zemva, J. Z., Schmoch, T. S., Uhle, F. U., Kihm, L. K., Morath, C. M., Nusshag, C. N., Zeier, M. Z., Bruckner, T. B., Mehrabi, A. M., Nawroth, P. N., Weigand, M. W., Hofer, S. H., Brenner, T. B., Fotopoulou, G., Poularas, I., Kokkoris, S., Brountzos, E., Elghonemi, M., Nilsson, K. F., Sandin, J., Gustafsson, L., Frithiof, R., Skorniakov, I., Varaksin, A., Vikulova, D., Shaikh, O., Whiteley, C., Ostermann, M., Di Lascio, G., Anicetti, L., Bonizzoli, M., Fulceri, G., Migliaccio, M. L., Sentina, P., Cozzolino, M., Peris, A., Khadzhynov, D., Halleck, F., Staeck, O., Lehner, L., Budde, K., Slowinski, T., Kindgen-Milles, D., Huysmans, N., Laenen, M. Vander, Helmschrodt, A., Boer, W., Debain, A., Jonckheer, J., Moeyersons, W., Van zwam, K., Puis, L., Staessens, K., Honoré, P. M., Spapen, H. D., De Waele, E., de Garibay, A. Perez Ruiz, Ende-Schneider, B., Schreiber, C., Kreymann, B., Bini, A., Votino, E., Steinberg, I., Vetrugno, L., Trunfio, D., Sidoti, A., Conroy, M., Marsh, B., and O’Flynn, J

Subjects
Critical Care and Intensive Care Medicine, Meeting Abstracts
Full Text
View/download PDF

20. Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

Author

Author et al, Bateman, R. M., Sharpe, M. D., Jagger, J. E., Ellis, C. G., Solé-Violán, J., López-Rodríguez, M., Herrera-Ramos, E., Ruíz-Hernández, J., Borderías, L., Horcajada, J., González-Quevedo, N., Rajas, O., Briones, M., Rodríguez de Castro, F., Rodríguez Gallego, C., Esen, F., Orhun, G., Ergin Ozcan, P., Senturk, E., Ugur Yilmaz, C., Orhan, N., Arican, N., Kaya, M., Kucukerden, M., Giris, M., Akcan, U., Bilgic Gazioglu, S., Tuzun, E., Riff, R., Naamani, O., Douvdevani, A., Takegawa, R., Yoshida, H., Hirose, T., Yamamoto, N., Hagiya, H., Ojima, M., Akeda, Y., Tasaki, O., Tomono, K., Shimazu, T., Ono, S., Kubo, T., Suda, S., Ueno, T., Ikeda, T., Ogura, H., Takahashi, H., Kang, J., Nakamura, Y., Kojima, T., Izutani, Y., Taniguchi, T., O, M., Dinter, C., Lotz, J., Eilers, B., Wissmann, C., Lott, R., Meili, M. M., Schuetz, P. S., Hawa, H., Sharshir, M., Aburageila, M., Salahuddin, N., Chantziara, V., Georgiou, S., Tsimogianni, A., Alexandropoulos, P., Vassi, A., Lagiou, F., Valta, M., Micha, G., Chinou, E., Michaloudis, G., Kodaira, A., Imaizumi, H., De la Torre-Prados, M. V., Garcia-De la Torre, A., Enguix-Armada, A., Puerto-Morlan, A., Perez-Valero, V., Garcia-Alcantara, A., Bolton, N., Dudziak, J., Bonney, S., Tridente, A., Nee, P., Nicolaes, G., Wiewel, M., Schultz, M., Wildhagen, K., Horn, J., Schrijver, R., Van der Poll, T., Reutelingsperger, C., Pillai, S., Davies, G., Mills, G., Aubrey, R., Morris, K., Williams, P., Evans, P., Gayat, E. G., Struck, J., Cariou, A., Deye, N., Guidet, B., Jabert, S., Launay, J., Legrand, M., Léone, M., Resche-Rigon, M., Vicaut, E., Vieillard-Baron, A., Mebazaa, A., Arnold, R., Capan, M., Linder, A., Akesson, P., Popescu, M., Tomescu, D., Sprung, C. L., Calderon Morales, R., Munteanu, G., Orenbuch-Harroch, E., Levin, P., Kasdan, H., Reiter, A., Volker, T., Himmel, Y., Cohen, Y., Meissonnier, J., Girard, L., Rebeaud, F., Herrmann, I., Delwarde, B., Peronnet, E., Cerrato, E., Venet, F., Lepape, A., Rimmelé, T., Monneret, G., Textoris, J., Beloborodova, N., Moroz, V., Osipov, A., Bedova, A., Sarshor, Y., Pautova, A., Sergeev, A., Chernevskaya, E., Odermatt, J., Bolliger, R., Hersberger, L., Ottiger, M., Christ-Crain, M., Mueller, B., Schuetz, P., Sharma, N. K., Tashima, A. K., Brunialti, M. K., Machado, F. R., Assuncao, M., Rigato, O., Salomao, R., Cajander, S. C., Rasmussen, G., Tina, E., Söderquist, B., Källman, J., Strålin, K., Lange, A. L., Sundén-Cullberg, J. S., Magnuson, A. M., Hultgren, O. H., Van der Geest, P., Mohseni, M., Linssen, J., De Jonge, R., Duran, S., Groeneveld, J., Miller, R., Lopansri, B. K., McHugh, L. C., Seldon, A., Burke, J. P., Johnston, J., Reece-Anthony, R., Bond, A., Molokhia, A., Mcgrath, C., Nsutebu, E., Bank Pedersen, P., Pilsgaard Henriksen, D., Mikkelsen, S., Touborg Lassen, A., Tincu, R., Cobilinschi, C., Ghiorghiu, Z., Macovei, R., Wiewel, M. A., Harmon, M. B., Van Vught, L. A., Scicluna, B. P., Hoogendijk, A. J., Zwinderman, A. H., Cremer, O. L., Bonten, M. J., Schultz, M. J., Juffermans, N. P., Wiersinga, W. J., Eren, G., Tekdos, Y., Dogan, M., Acicbe, O., Kaya, E., Hergunsel, O., Alsolamy, S., Ghamdi, G., Alswaidan, L., Alharbi, S., Alenezi, F., Arabi, Y., Heaton, J., Boyce, A., Nolan, L., Dukoff-Gordon, A., Dean, A., Mann Ben Yehudah, T., Fleischmann, C., Thomas-Rueddel, D., Haas, C., Dennler, U., Reinhart, K., Suntornlohanakul, O., Khwannimit, B., Breckenridge, F., Puxty, A., Szturz, P., Folwarzcny, P., Svancara, J., Kula, R., Sevcik, P., Caneva, L., Casazza, A., Bellazzi, E., Marra, S., Pagani, L., Vetere, M., Vanzino, R., Ciprandi, D., Preda, R., Boschi, R., Carnevale, L., Lopez, V., Aguilar Arzapalo, M., Barradas, L., Escalante, A., Gongora, J., Cetina, M., Adamik, B, Jakubczyk, D, Kübler, A, Radford, A., Lee, T., Singer, J., Boyd, J., Fineberg, D., Williams, M., Russell, J., Scarlatescu, E., Droc, G., Arama, S., Müller, M., Straat, M., Zeerleder, S. S., Fuchs, C. F., Scheer, C. S., Wauschkuhn, S. W., Vollmer, M. V., Meissner, K. M., Kuhn, S. K., Hahnenkamp, K. H., Rehberg, S. R., Gründling, M. G., Hamaguchi, S., Gómez-Sánchez, E., Heredia-Rodríguez, M., Álvarez-Fuente, E., Lorenzo-López, M., Gómez-Pesquera, E., Aragón-Camino, M., Liu-Zhu, P., Sánchez-López, A., Hernández-Lozano, A., Peláez-Jareño, M. T., Tamayo, E., Thomas-Rüddel, D. O., Adora, V., Kar, A., Chakraborty, A., Roy, S., Bandyopadhyay, A., Das, M., BenYehudah, G., Salim, M., Kumar, N., Arabi, L., Burger, T., Lephart, P., Toth-martin, E., Valencia, C., Hammami, N., Blot, S., Vincent, J. L., Lambert, M. L., Brunke, J., Riemann, T., Roschke, I., Nimitvilai, S., Jintanapramote, K., Jarupongprapa, S., Adukauskiene, D., Valanciene, D., Bose, G., Lostarakos, V., Carr, B., Khedher, S., Maaoui, A., Ezzamouri, A., Salem, M., Chen, J., Cranendonk, D. R., Day, M., Penrice, G., Roy, K., Robertson, P., Godbole, G., Jones, B., Booth, M., Donaldson, L., Kawano, Y., Ishikura, H., Al-Dorzi, H., Almutairi, M., Alhamadi, B., Crizaldo Toledo, A., Khan, R., Al Raiy, B., Talaie, H., Van Oers, J. A., Harts, A., Nieuwkoop, E., Vos, P., Boussarsar, Y., Boutouta, F., Kamoun, S., Mezghani, I., Koubaji, S., Ben Souissi, A., Riahi, A., Mebazaa, M. S., Giamarellos-Bourboulis, E., Tziolos, N., Routsi, C., Katsenos, C., Tsangaris, I., Pneumatikos, I., Vlachogiannis, G., Theodorou, V., Prekates, A., Antypa, E., Koulouras, V., Kapravelos, N., Gogos, C., Antoniadou, E., Mandragos, K., Armaganidis, A., Robles Caballero, A. R., Civantos, B., Figueira, J. C., López, J., Silva-Pinto, A., Ceia, F., Sarmento, A., Santos, L., Almekhlafi, G., Sakr, Y., Baharoon, S., Aldawood, A., Matroud, A., Alchin, J., Al Johani, S., Balkhy, H., Yousif, S. Y., Alotabi, B. O., Alsaawi, A. S., Ang, J., Curran, M. D., Enoch, D., Navapurkar, V., Morris, A., Sharvill, R., Astin, J., Patel, J., Kruger, C., O’Neal, J., Rhodes, H., Jancik, J., François, B., Laterre, P. F., Eggimann, P., Torres, A., Sánchez, M., Dequin, P. F., Bassi, G. L., Chastre, J., Jafri, H. S., Ben Romdhane, M., Douira, Z., Bousselmi, M., Vakalos, A., Avramidis, V., Craven, T. H., Wojcik, G., Kefala, K., McCoubrey, J., Reilly, J., Paterson, R., Inverarity, D., Laurenson, I., Walsh, T. S., Mongodi, S., Bouhemad, B., Orlando, A., Stella, A., Via, G., Iotti, G., Braschi, A., Mojoli, F., Haliloglu, M., Bilgili, B., Kasapoglu, U., Sayan, I., Süzer Aslan, M., Yalcin, A., Cinel, I., Ellis, H. E., Bauchmuller, K., Miller, D., Temple, A., Luyt, C. E., Singer, M., Nassar, Y., Ayad, M. S., Trifi, A., Abdellatif, S., Daly, F., Nasri, R., Ben Lakhal, S., Gul, F., Kuzovlev, A., Shabanov, A., Polovnikov, S., Kadrichu, N., Dang, T., Corkery, K., Challoner, P., Bassi, G. Li, Aguilera, E., Chiurazzi, C., Travierso, C., Motos, A., Fernandez, L., Amaro, R., Senussi, T., Idone, F., Bobi, J., Rigol, M., Hodiamont, C. J., Janssen, J. M., Bouman, C. S., Mathôt, R. A., De Jong, M. D., Van Hest, R. M., Payne, L., Fraser, G. L., Tudor, B., Lahner, M., Roth, G., Krenn, C., Jault, P., Gabard, J., Leclerc, T., Jennes, S., Que, Y., Rousseau, A., Ravat, F., Eissa, A., Al-Harbi, S., Aldabbagh, T., Abdellatif., S., Paramba, F., Purayil, N., Naushad, V., Mohammad, O., Negi, V., Chandra, P., Kleinsasser, A., Witrz, M. R., Buchner-Doeven, J. F., Tuip-de Boer, A. M., Goslings, J. C., Van Hezel, M., Boing, A, Van Bruggen, R, Juffermans, N, Markopoulou, D., Venetsanou, K., Kaldis, V., Koutete, D., Chroni, D., Alamanos, I., Koch, L., Walter, E., Maekawa, K., Hayakawa, M., Kushimoto, S., Shiraishi, A., Kato, H., Sasaki, J., Matauoka, T., Uejima, T., Morimura, N., Hagiwara, A., Takeda, M., Tarabrin, O., Shcherbakow, S., Gavrychenko, D., Mazurenko, G., Ivanova, V., Chystikov, O., Plourde, C., Lessard, J., Chauny, J., Daoust, R., Kropman, L., In het Panhuis, L., Konings, J., Huskens, D., Schurgers, E., Roest, M., De Laat, B., Lance, M., Durila, M., Lukas, P., Astraverkhava, M., Jonas, J., Budnik, I., Shenkman, B., Hayami, H., Koide, Y., Goto, T., Iqbal, R., Alhamdi, Y., Venugopal, N., Abrams, S., Downey, C., Toh, C. H., Welters, I. D., Bombay, V. B., Chauny, J. M., Daoust, R. D., Lessard, J. L., Marquis, M. M., Paquet, J. P., Siemens, K., Sangaran, D., Hunt, B. J., Durward, A., Nyman, A., Murdoch, I. A., Tibby, S. M., Ampatzidou, F., Moisidou, D., Dalampini, E., Nastou, M., Vasilarou, E., Kalaizi, V., Chatzikostenoglou, H., Drossos, G., Spadaro, S., Fogagnolo, A., Fiore, T., Schiavi, A., Fontana, V., Taccone, F., Volta, C., Chochliourou, E., Volakli, E., Violaki, A., Samkinidou, E., Evlavis, G., Panagiotidou, V., Sdougka, M., Mothukuri, R., Battle, C., Guy, K., Wijesuriya, J., Keogh, S., Docherty, A., O’Donnell, R., Brunskill, S., Trivella, M., Doree, C., Holst, L., Parker, M., Gregersen, M., Almeida, J., Walsh, T., Stanworth, S., Moravcova, S., Mansell, J., Rogers, A., Smith, R. A., Hamilton-Davies, C., Omar, A., Allam, M., Bilala, O., Kindawi, A., Ewila, H., Malamas, A., Ferreira, G., Caldas, J., Fukushima, J., Osawa, E. A., Arita, E., Camara, L., Zeferino, S., Jardim, J., Gaioto, F., Dallan, L., Jatene, F. B., Kalil Filho, R., Galas, F., Hajjar, L. A., Mitaka, C., Ohnuma, T., Murayama, T., Kunimoto, F., Nagashima, M., Takei, T., Tomita, M., Mahmoud, K., Hanoura, S., Sudarsanan, S., Sivadasan, P., Othamn, H., Shouman, Y., Singh, R., Al Khulaifi, A., Mandel, I., Mikheev, S., Suhodolo, I., Kiselev, V., Svirko, Y., Podoksenov, Y., Jenkins, S. A., Griffin, R., Tovar Doncel, M. S., Lima, A., Aldecoa, C., Ince, C., Taha, A., Shafie, A., Mostafa, M., Syed, N., Hon, H., Righetti, F., Colombaroli, E., Castellano, G., Hravnak, M., Chen, L. C., Dubrawski, A. D., Clermont, G. C., Pinsky, M. R., Gonzalez, S., Macias, D., Acosta, J., Jimenez, P., Loza, A., Lesmes, A., Lucena, F., Leon, C., Bastide, M., Richecoeur, J., Frenoy, E., Lemaire, C., Sauneuf, B., Tamion, F., Nseir, S., Du Cheyron, D., Dupont, H., Maizel, J., Shaban, M., Kolko, R., AbuRageila, M., AlHussain, A., Mercado, P., Kontar, L., Titeca, D., Brazier, F., Riviere, A., Joris, M., Soupison, T., De Cagny, B., Slama, M., Wagner, J., Körner, A., Kubik, M., Kluge, S., Reuter, D., Saugel, B., Tran, T., De Bels, D., Cudia, A., Strachinaru, M., Ghottignies, P., Devriendt, J., Pierrakos, C., Martínez González, Ó., Blancas, R., Luján, J., Ballesteros, D., Martínez Díaz, C., Núñez, A., Martín Parra, C., López Matamala, B., Alonso Fernández, M., Chana, M., Huber, W., Eckmann, M., Elkmann, F., Gruber, A., Klein, I., Schmid, R. M., Lahmer, T., Moller, P. W., Sondergaard, S., Jakob, S. M., Takala, J., Berger, D., Bastoni, D., Aya, H., Toscani, L., Pigozzi, L., Rhodes, A., Cecconi, M., Ostrowska, C., Abbas, A., Mellinghoff, J., Ryan, C., Dawson, D., Cronhjort, M., Wall, O., Nyberg, E., Zeng, R., Svensen, C., Mårtensson, J., Joelsson-Alm, E., Parenti, N., Palazzi, C., Amidei, L. A., Borrelli, F. B., Campanale, S. C., Tagliazucchi, F. T., Sedoni, G. S., Lucchesi, D. L., Carella, E. C., Luciani, A. L, Mackovic, M., Maric, N., Bakula, M., Grounds, R. M., Fletcher, N., Avard, B., Zhang, P., Mezidi, M., Charbit, J., Ould-Chikh, M., Deras, P., Maury, C., Martinez, O., Capdevila, X., Hou, P., Linde-Zwirble, W. Z., Douglas, I. D., Shapiro, N. S., Ben Aicha, Y., Laribi, B., Jeribi, B., Pereira, C., Marinho, R., Antunes, R., Marinho, A., Crivits, M., Raes, M., Decruyenaere, J., Hoste, E., Bagin, V., Rudnov, V., Savitsky, A., Astafyeva, M., Korobko, I., Vein, V., Kampmeier, T., Arnemann, P., Hessler, M., Wald, A., Bockbreder, K., Morelli, A., Van Aken, H., Rehberg, S., Ertmer, C., Reddy, S., Bailey, M., Beasley, R., Bellomo, R., Mackle, D., Psirides, A., Young, P., Venkatesh, H., Ramachandran, S., Basu, A., Nair, H., Egan, S., Bates, J., Oliveira, S., Rangel Neto, N. R., Reis, F. Q., Lee, C. P., Lin, X. L., Choong, C., Eu, K. M., Sim, W. Y., Tee, K. S., Pau, J., Abisheganaden, J., Maas, K., De Geus, H., Lafuente, E., Moura, J., Doris, T. E., Monkhouse, D., Shipley, T., Kardasz, S., Gonzalez, I, Stads, S., Groeneveld, A. J., Elsayed, I., Ward, N., Raithatha, A., Steuber, A., Pelletier, C., Schroeder, S., Michael, E., Slowinski, T., Kindgen-Milles, D., Ghabina, S., Turani, F., Belli, A., Busatti, S., Barettin, G., Candidi, F., Gargano, F., Barchetta, R., Falco, M., Demirkiran, O., Kosuk, M., Bozbay, S., Weber, V., Hartmann, J., Harm, S., Linsberger, I., Eichhorn, T., Valicek, G., Miestinger, G., Hoermann, C., Faenza, S., Ricci, D., Mancini, E., Gemelli, C., Cuoghi, A., Magnani, S., Atti, M., Laddomada, T., Doronzio, A., Balicco, B., Gruda, M. C., O’Sullivan, P., Dan, V. P., Guliashvili, T., Scheirer, A., Golobish, T. D., Capponi, V. J., Chan, P. P., Kogelmann, K., Drüner, M., Jarczak, D., Belli, A. B., Martni, S. M., Cotticelli, V. C., Mounajergi, F., Morimoto, S., Hussain, I., Nadeem, A., Ghorab, K., Maghrabi, K., Kloesel, S. K., Goldfuss, C., Stieglitz, A., Stieglitz, A. S., Krstevska, L., Albuszies, G., Jimmy, G., Izawa, J., Iwami, T., Uchino, S., Takinami, M., Kitamura, T., Kawamura, T., Powell-Tuck, J. G., Crichton, S., Raimundo, M., Camporota, L., Wyncoll, D., Ostermann, M., Hana, A., De Geus, H. R., Aydogdu, M., Boyaci, N., Yuksel, S., Gursel, G., Cayci Sivri, A. B., Meza-Márquez, J., Nava-López, J., Carrillo-Esper, R., Dardashti, A., Grubb, A., Wetzstein, M., Peters, E., Njimi, H., Pickkers, P., Waraich, M., Doyle, J., Samuels, T., Forni, L., Desai, N., Baumber, R., Gunning, P., Sell, A., Lin, S., Torrence, H., O’Dwyer, M., Kirwan, C., Prowle, J., Kim, T., O’Connor, M. E., Hewson, R. W., Kirwan, C. J., Pearse, R. M., Maksoud, M., Uzundere, O., Memis, D., Ýnal, M., Gultekin, A., Turan, N., Aydin, M. A., Basar, H., Sencan, I., Kapuagasi, A., Ozturk, M., Uzundurukan, Z., Gokmen, D., Ozcan, A., Kaymak, C., Artemenko, V. A., Budnyuk, A., Pugh, R., Bhandari, S., Mauri, T., Turrini, C., Langer, T., Taccone, P., Volta, C. A., Marenghi, C., Gattinoni, L., Pesenti, A., Sweeney, L., O’Sullivan, A., Kelly, P., Mukeria, E., MacLoughlin, R., Pfeffer, M., Thomas, J. T., Bregman, G. B., Karp, G. K., Kishinevsky, E. K., Stavi, D. S., Adi, N. A., Poropat, T., Knafelj, R., Llopart, E., Batlle, M., De Haro, C., Mesquida, J., Artigas, A., Pavlovic, D., Lewerentz, L., Spassov, A., Schneider, R., De Smet, S., De Raedt, S., Derom, E., Depuydt, P, Oeyen, S., Benoit, D., Gobatto, A., Besen, B., Tierno, P., Melro, L., Mendes, P., Cadamuro, F., Park, M., Malbouisson, L. M., Civantos, B. C., Lopez, J. L., Robles, A., Figueira, J., Yus, S., Garcia, A., Oglinda, A., Ciobanu, G., Oglinda, C., Schirca, L., Sertinean, T., Lupu, V., Wolny, M., Pagano, A., Numis, F., Visone, G., Saldamarco, L., Russo, T., Porta, G., Paladino, F., Bell, C., Liu, J., Debacker, J., Lee, C., Tamberg, E., Campbell, V., Mehta, S., Kara, Ý., Yýldýrým, F., Zerman, A., Güllü, Z., Boyacý, N., Basarýk Aydogan, B., Gaygýsýz, Ü., Gönderen, K., Arýk, G., Turkoglu, M., Aygencel, G., Ülger, Z., Isýkdogan, Z., Özdedeoglu, Ö., Badoglu, M., Gaygýsýz, U., Kongpolprom, N., Sittipunt, C., Eden, A., Kokhanovsky, Y., Bursztein – De Myttenaere, S., Pizov, R., Neilans, L., MacIntyre, N., Radosevich, M., Wanta, B., Meyer, T., Smischney, N., Brown, D., Diedrich, D., Fuller, A., McLindon, P., Sim, K., Shoaeir, M., Noeam, K., Mahrous, A., Matsa, R., Ali, A., Dridi, C., Haddad, F., Pérez-Calatayud, A., Zepeda-Mendoza, A., Diaz-Carrillo, M., Arch-Tirado, E., Carbognin, S., Pelacani, L., Zannoni, F., Agnoli, A., Gagliardi, G., Cho, R., Adams, A., Lunos, S., Ambur, S., Shapiro, R., Prekker, M., Thijssen, M., Janssen, L., Foudraine, N., Voscopoulos, C. J., Freeman, J., George, E., Eversole, D., Muttini, S., Bigi, R., Villani, G., Patroniti, N., Williams, G., George, E, Waldmann, A., Böhm, S., Windisch, W., Strassmann, S., Karagiannidis, C., Karagiannidis, C. K., Waldmann, A. W., Böhm, S. B., Windisch, W. W., Persson, P., Lundin, S., Stenqvist, O., Serra, C. S., Pagano, A. P., Masarone, M. M., Rinaldi, L. R., Amelia, A. A., Fascione, M. F., Adinolfi, L. A., Ruggiero, E. R., Asota, F., O’Rourke, K., Ranjan, S., Morgan, P., DeBacker, J. W., O’Neill, L., Munshi, L., Burry, L., Fan, E., Poo, S., Mahendran, K., Fowles, J., Gerrard, C., Vuylsteke, A., Loveridge, R., Chaddock, C., Patel, S., Kakar, V., Willars, C., Hurst, T., Park, C., Best, T., Vercueil, A., Auzinger, G., Borgman, A., Proudfoot, A. G., Grins, E., Emiley, K. E., Schuitema, J., Fitch, S. J., Marco, G., Sturgill, J., Dickinson, M. G., Strueber, M., Khaghani, A., Wilton, P., Jovinge, S. M., Sampson, C., Harris-Fox, S., Cove, M. E., Vu, L. H., Sen, A., Federspiel, W. J., Kellum, J. A., Mazo Torre, C., Riera, J., Ramirez, S., Borgatta, B., Lagunes, L., Rello, J., Kuzovlev, A. K., Goloubev, A., Nenchuk, S., Karavana, V., Glynos, C., Asimakos, A., Pappas, K., Vrettou, C., Magkou, M., Ischaki, E., Stathopoulos, G., Zakynthinos, S., Kozhevnikova, I., Dalla Corte, F., Grasso, S., Casolari, P., Caramori, G., Andrianjafiarinoa, T., Randriamandrato, T., Rajaonera, T., El-Dash, S., Costa, E. L. V., Tucci, M. R., Leleu, F, Kontar, L, Bacari-Risal, G., Amato, M., El Dash, S., Remmington, Fischer, A., Squire, S., Boichat, M., Honzawa, H., Yasuda, H., Adati, T., Suzaki, S., Horibe, M., Sasaki, M., Sanui, M., Daniel, J., Miranda, H., Milinis, K., Cooper, M., Williams, G. R., McCarron, E., Simants, S., Patanwala, I., Welters, I., Su, Y., Fernández Villanueva, J., Fernández Garda, R., López Lago, A., Rodríguez Ruíz, E., Hernández Vaquero, R., Tomé Martínez de Rituerto, S., Varo Pérez, E., Lefel, N., Schaap, F., Bergmans, D., Olde Damink, S., Van de Poll, M., Tizard, K., Lister, C., Poole, L., Ringaitiene, D., Gineityte, D., Vicka, V., Norkiene, I., Sipylaite, J., O’Loughlin, A., Maraj, V., Dowling, J., Velasco, M. B., Dalcomune, D. M., Dias, E. B., Fernandes, S. L., Oshima, T., Graf, S., Heidegger, C., Genton, L., Karsegard, V., Dupertuis, Y., Pichard, C., Friedli, N., Stanga, Z., Vandersteen, L., Stessel, B., Evers, S., Van Assche, A., Jamaer, L., Dubois, J., Castro, H., Valente, J., Martins, P., Casteloes, P., Magalhaes, C., Cabral, S., Santos, M., Oliveira, B., Salgueiro, A., Duarte, S., Castro, S., Melo, M., Gray, S., Maipang, K., Bhurayanontachai, R., Grädel, L. G., Schütz, P., Langlois, P., Manzanares, W., Lemieux, M., Elke, G., Bloos, F., Heyland, D., Aramendi, I., Babo, N., Hoshino, M., Haraguchi, Y., Kajiwara, S., Mitsuhashi, T., Tsubata, T., Aida, M., Rattanapraphat, T., Kongkamol, C., Xavier, B., Koutsogiannidis, C., Moschopoulou, M., Taskin, G., Çakir, M., Güler, AK, Taskin, A., Öcal, N., Özer, S., Yamanel, L., Wong, J. M., Fitton, C., Anwar, S., Stacey, S., Aggou, M., Fyntanidou, B., Patsatzakis, S., Oloktsidou, E., Lolakos, K., Papapostolou, E., Grosomanidis, V., Gaudry, S., Desailly, V., Pasquier, P., Brun, PB, Tesnieres, AT, Ricard, JD, Dreyfuss, D., Mignon, A., White, J. C, Stilwell, A., Friedlaender, G., Peters, M., Stipulante, S., Delfosse, A., Donneau, AF, Ghuysen, A., Feldmann, C., Freitag, D., Dersch, W., Irqsusi, M., Eschbach, D., Steinfeldt, T., Wulf, H., Wiesmann, T., Cholkraisuwat, J., Beitland, S., Nakstad, E., Stær-Jensen, H., Drægni, T., Andersen, G., Jacobsen, D., Brunborg, C., Waldum-Grevbo, B., Sunde, K., Hoyland, K., Pandit, D., Hayakawa, K., Kotzampassi, K., Loukipoudi, L., Doumaki, E., Admiraal, M. M., Van Assen, M., Van Putten, M. J., Tjepkema-Cloostermans, M., Van Rootselaar, A. F., Ragusa, F., Marudi, A., Baroni, S., Gaspari, A., Bertellini, E., Abdullah, T., Abdel Monem, S., Alcorn, S., McNeill, S., Russell, S., Eertmans, W., Genbrugge, C., Meex, I., Dens, J., Jans, F., De Deyne, C., Avard, B, Burns, R, Patarchi, A., Spina, T., Tanaka, H., Otani, N., Ode, S., Ishimatsu, S., Cho, J., Moon, J. B., Park, C. W., Ohk, T. G., Shin, M. C., Won, M. H., Dakova, S., Ramsheva, Z., Ramshev, K., Marudi, A, Baroni, S, Gaspari, A, Bertellini, E, Ozcan, P. E., Sencer, S., Ulusoy, C., Fallenius, M., Skrifvars, M. B., Reinikainen, M., Bendel, S., Raj, R., Abu-Habsa, M., Hymers, C., Borowska, A., Sivadhas, H., Sahiba, S., Perkins, S., Rubio, J., Rubio, J. A., Sierra, R., English, S., Chasse, M., Turgeon, A., Lauzier, F., Griesdale, D., Garland, A., Fergusson, D., Zarychanski, R., Tinmouth, A., Van Walraven, C., Montroy, K., Ziegler, J., Dupont Chouinard, R., Carignan, R., Dhaliwal, A., Lum, C., Sinclair, J., Pagliarello, G., McIntyre, L., Groza, T., Moreau, N., Castanares-Zapatero, D., Hantson, P., Carbonara, M., Ortolano, F., Zoerle, T., Magnoni, S., Pifferi, S., Conte, V., Stocchetti, N., Carteron, L., Suys, T., Patet, C., Quintard, H., Oddo, M., Spatenkova, V., Pokorna, E., Suchomel, P., Ebert, N., Bylinski, T., Hawthorne, C., Shaw, M., Piper, I., Kinsella, J., Kink, A. K., Rätsep, I. R., Boutin, A., Moore, L., Lacroix, J., Lessard-Bonaventure, P., Turgeon, A. F., Green, R., Erdogan, M., Butler, M., Desjardins, P., Fergusson, D. A., Goncalves, B., Vidal, B., Valdez, C., Rodrigues, A. C., Miguez, L., Moralez, G., Hong, T., Kutz, A., Hausfater, P., Amin, D., Struja, T., Haubitz, S., Huber, A., Brown, T., Collinson, J., Pritchett, C., Slade, T., Le Guen, M., Hellings, S., Ramsaran, R., Alsheikhly, A., Abe, T., Kanapeckaite, L., Bahl, R., Russell, M. Q., Real, K. J., Lyon, R. M., Oveland, N. P., Penketh, J., Mcdonald, M., Kelly, F., Alfafi, M., Almutairi, W., Alotaibi, B., Van den Berg, A. E, Schriel, Y., Dawson, L., Meynaar, I. A., Silva, D., Fernandes, S., Gouveia, J., Santos Silva, J., Foley, J., Kaskovagheorgescu, A., Evoy, D., Cronin, J., Ryan, J., Huck, M., Hoffmann, C., Renner, J., Laitselart, P., Donat, N., Cirodde, A., Schaal, J. V., Masson, Y., Nau, A., Howarth, O., Davenport, K., Jeanrenaud, P., Raftery, S., MacTavish, P., Devine, H., McPeake, J., Daniel, M., Quasim, T., Alrabiee, S., Alrashid, A., Gundogan, O., Bor, C., Akýn Korhan, E., Demirag, K., Uyar, M., Frame, F., Ashton, C., Bergstrom Niska, L., Dilokpattanamongkol, P., Suansanae, T., Suthisisang, C., Morakul, S., Karnjanarachata, C., Tangsujaritvijit, V., Mahmood, S., Al Thani, H., Almenyar, A., Morton, S. E., Chiew, Y. S., Pretty, C., Chase, J. G., Shaw, G. M., Kordis, P., Grover, V., Kuchyn, I., Bielka, K., Aidoni, Z., Stavrou, G., Skourtis, C., Lee, S. D., Williams, K., Weltes, I. D., Berhane, S., Arrowsmith, C., Peters, C., Robert, S., Panerai, R. B., Robinson, T. G., Borg-Seng-Shu, E., De Lima Oliveira, M., Mian, N. C., Nogueira, R., Zeferino, S. P., Jacobsen Teixeira, M., Killeen, P., McPhail, M., Bernal, W., Maggs, J., Wendon, J., Hughes, T., Taniguchi, L. U., Siqueira, E. M., Vieira Jr, J. M., Azevedo, L. C., Ahmad, A. N., Helme, E., Hadfield, S., Shak, J., Senver, C., Howard-Griffin, R., Wacharasint, P., Fuengfoo, P., Sukcharoen, N., Rangsin, R., Sbiti-Rohr, D., Na, H., Song, S., Lee, S., Jeong, E., Lee, K., Zoumpelouli, E., Volakli, E. A, Chrysohoidou, V., Charisopoulou, K., Kotzapanagiotou, E., Manavidou, K., Stathi, Z., AlGhamdi, B., Marashly, Q., Zaza, K., Khurshid, M., Ali, Z., Malgapo, M., Jamil, M., Shafquat, A., Shoukri, M., Hijazi, M., Rocha, F. A., Ebecken, K., Rabello, L. S., Lima, M. F., Hatum, R., De Marco, F. V., Alves, A., Pinto, J. E., Godoy, M., Brasil, P. E., Bozza, F. A., Salluh, J. I., Soares, M., Krinsley, J., Kang, G., Perry, J., Hines, H., Wilkinson, K. M., Tordoff, C., Sloan, B., Bellamy, M. C., Moreira, E., Verga, F., Barbato, M., Burghi, G., Soares, M, Silva, U. V., Torelly, A. P., Kahn, J. M., Angus, D. C., Knibel, M. F., Marshall, R., Gilpin, T., Mota, D., Loureiro, B., Dias, J., Afonso, O., Coelho, F., Martins, A., Faria, F., Al Orainni, H., AlEid, F., Tlaygeh, H., Itani, A., Hejazi, A., Messika, J., Ricard, J. D., Guillo, S., Pasquet, B., Dubief, E., Tubach, F., James, K., Temblett, P., Davies, L., Lynch, C., Pereira, S., Cavaco, S., Fernandes, J., Moreira, I., Almeida, E., Seabra Pereira, F., Malheiro, M., Cardoso, F., Aragão, I., Cardoso, T., Fister, M., Muraray Govind, P., Brahmananda Reddy, N., Pratheema, R., Arul, E. D., Devachandran, J., Chin-Yee, N., D’Egidio, G., Thavorn, K., Kyeremanteng, K., Murchison, A. G., Swalwell, K., Mandeville, J., Stott, D., Guerreiro, I., Goossens, C., Marques, M. B., Derde, S., Vander Perre, S., Dufour, T., Thiessen, S. E., Güiza, F., Janssens, T., Hermans, G., Vanhorebeek, I., De Bock, K., Van den Berghe, G., Langouche, L., Miles, B., Madden, S., Weiler, M., Marques, P., Rodrigues, C., Boeira, M., Brenner, K., Leães, C., Machado, A., Townsend, R., Andrade, J., Kishore, R., Fenlon, C., Fiks, T., Ruijter, A., Te Raa, M., Spronk, P., Docherty, P., Dickson, J., Moltchanova, E., Scarrot, C., Hall, T., Ngu, W. C., Jack, J. M., Pavli, A., Gee, X., Akin Korhan, E., Shirazy, M., Fayed, A., Gupta, S., Kaushal, A., Dewan, S., Varma, A., Ghosh, E., Yang, L., Eshelman, L., Lord, B., Carlson, E., Broderick, R., Ramos, J., Forte, D., Yang, F., Feeney, J., Wilkinson, K., Shuker, K., Faulds, M., Bryden, D., England, L., Shuker, K, Tridente, A, Faulds, M, Matheson, A, Gaynor, J., Bryden, D, ᅟ, S South Yorkshire Hospitals Research Collaboration, Peroni, B., Daglius-Dias, R., Miranda, L., Cohen, C., Carvalho, C., Velasco, I., Kelly, J. M., Neill, A., Rubenfeld, G., Masson, N., Min, A., Boezeman, E., Hofhuis, J., Hovingh, A., De Vries, R., Cabral-Campello, G., Van Mol, M., Nijkamp, M., Kompanje, E., Ostrowski, P., Kiss, K., Köves, B., Csernus, V., Molnár, Z., Hoydonckx, Y., Vanwing, S., Medo, V., Galvez, R., Miranda, J. P., Stone, C., Wigmore, T., Arunan, Y., Wheeler, A., Wong, Y., Poi, C., Gu, C., Molmy, P., Van Grunderbeeck, N., Nigeon, O., Lemyze, M., Thevenin, D., Mallat, J., Correa, M., Carvalho, R. T., Fernandez, A., McBride, C., Koonthalloor, E., Walsh, C., Webber, A., Ashe, M., Smith, K., Volakli, E. A., Dimitriadou, M., Mantzafleri, P., Vrani, O., Arbouti, A., Varsami, T., Bollen, J. A., Van Smaalen, T. C., De Jongh, W. C., Ten Hoopen, M. M., Ysebaert, D., Van Heurn, L. W., Van Mook, W. N., Roze des Ordons, A., Couillard, P., Doig, C., Van Keer, R. V., Deschepper, R. D., Francke, A. F., Huyghens, L. H., Bilsen, J. B., Nyamaizi, B., Dalrymple, C., Dobru, A., Marrinan, E., Ankuli, A., Struthers, R., Crawford, R., Mactavish, P., Morelli, P., Degiovanangelo, M., Lemos, F., MArtinez, V., Cabrera, J., Rutten, A., Van Ieperen, S., De Geer, S., Van Vugt, M., Der Kinderen, E., Giannini, A., Miccinesi, G, Marchesi, T, and Prandi, E

Subjects
health care facilities, manpower, and services, education, Erratum, Critical Care and Intensive Care Medicine, reproductive and urinary physiology, humanities, health care economics and organizations
Full Text
View/download PDF

22. Exploiting evolutionary steering to induce collateral drug sensitivity in cancer

Author

Javier Fernández-Mateos, Andrea Sottoriva, Carlo C. Maley, Inmaculada Spiteri, Udai Banerji, Benjamin Werner, Ahmet Acar, Mark Stubbs, Luca Magnani, Sung Pil Hong, Giulio Caravagna, Adam Stewart, Nicholas A. Trahearn, Daniel Nichol, Nicola Valeri, Georgios Vlachogiannis, Rosemary Burke, George D. Cresswell, Iros Barozzi, Acar, A., Nichol, D., Fernandez-Mateos, J., Cresswell, G. D., Barozzi, I., Hong, S. P., Trahearn, N., Spiteri, I., Stubbs, M., Burke, R., Stewart, A., Caravagna, G., Werner, B., Vlachogiannis, G., Maley, C. C., Magnani, L., Valeri, N., Banerji, U., and Sottoriva, A.

Subjects
0301 basic medicine, Lung Neoplasms, EGFR BLOCKADE, Stochastic Processe, TUMOR HETEROGENEITY, Drug Resistance, General Physics and Astronomy, Drug resistance, Pyridone, Genome informatics, Somatic evolution in cancer, Antineoplastic Agent, 0302 clinical medicine, TARGETED THERAPY, Theoretical, Models, lcsh:Science, Stochastic modelling, media_common, Pyrimidinone, education.field_of_study, Multidisciplinary, Gefitinib, 3. Good health, Multidisciplinary Sciences, 030220 oncology & carcinogenesis, Science & Technology - Other Topics, Molecular Medicine, Lung cancer, medicine.drug, Human, Drug, Genotype, Evolution, Pyridones, media_common.quotation_subject, Science, CELL LUNG-CANCER, Population, COMPETITION, Antineoplastic Agents, Computational biology, Pyrimidinones, Biology, Clonal Evolution, Computational Biology, Computer Simulation, Humans, Models, Theoretical, Stochastic Processes, Drug Resistance, Neoplasm, Evolution, Molecular, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, medicine, Sensitivity (control systems), Evolutionary dynamics, education, Science & Technology, MUTATIONS, Cancer, Molecular, General Chemistry, medicine.disease, Lung Neoplasm, 030104 developmental biology, COPY NUMBER, Computer modelling, Neoplasm, lcsh:Q, INHIBITORS, ACQUIRED-RESISTANCE
Abstract

Drug resistance mediated by clonal evolution is arguably the biggest problem in cancer therapy today. However, evolving resistance to one drug may come at a cost of decreased fecundity or increased sensitivity to another drug. These evolutionary trade-offs can be exploited using ‘evolutionary steering’ to control the tumour population and delay resistance. However, recapitulating cancer evolutionary dynamics experimentally remains challenging. Here, we present an approach for evolutionary steering based on a combination of single-cell barcoding, large populations of 108–109 cells grown without re-plating, longitudinal non-destructive monitoring of cancer clones, and mathematical modelling of tumour evolution. We demonstrate evolutionary steering in a lung cancer model, showing that it shifts the clonal composition of the tumour in our favour, leading to collateral sensitivity and proliferative costs. Genomic profiling revealed some of the mechanisms that drive evolved sensitivity. This approach allows modelling evolutionary steering strategies that can potentially control treatment resistance., Evolutionary steering uses therapies to control tumour evolution by exploiting trade-offs. Here, using a barcoding approach applied to large cell populations, the authors explore evolutionary steering in lung cancer cells treated with EGFR inhibitors.

Published
2020
Full Text
View/download PDF

23. Modulation of biliary cancer chemo-resistance through microRNA-mediated rewiring of the expansion of CD133+ cells

Author

Andrea Lampis, Nicola Valeri, Stuart J. Forbes, Vladimir Kirkin, Vincenzo Cardinale, Pietro Carotenuto, Lorenza Rimassa, Armando Santoro, Vincenza Guzzardo, Sofia Ventura, Umberto Cillo, Ian Said-Huntingford, Massimo Roncalli, Domenico Alvaro, Vasiliki Michalarea, Luciano Cascione, Massimiliano Salati, Luke Boulter, Paul Workman, Chiara Braconi, Daniele Costantini, Michele Ghidini, Paul A. Clarke, Rachel V. Guest, David Cunningham, Georgios Vlachogiannis, Somaieh Hedayat, Guido Carpino, Elizabeth C Smyth, Matteo Fassan, Aldo Scarpa, Robert te Poele, Ruwaida Begum, Caterina Vicentini, Francesco Trevisani, Jens C. Hahne, Carotenuto, P., Hedayat, S., Fassan, M., Cardinale, V., Lampis, A., Guzzardo, V., Vicentini, C., Scarpa, A., Cascione, L., Costantini, D., Carpino, G., Alvaro, D., Ghidini, M., Trevisani, F., Te Poele, R., Salati, M., Ventura, S., Vlachogiannis, G., Hahne, J. C., Boulter, L., Forbes, S. J., Guest, R. V., Cillo, U., Said-Huntingford, I., Begum, R., Smyth, E., Michalarea, V., Cunningham, D., Rimassa, L., Santoro, A., Roncalli, M., Kirkin, V., Clarke, P., Workman, P., Valeri, N., and Braconi, C.

Subjects
High-Throughput Screening Assay, 0301 basic medicine, Xenograft Model Antitumor Assay, Cell Survival, Antineoplastic Agents, Cancer Stem Cell, chemotherapy, Deoxycytidine, Cholangiocarcinoma, FZD8, MIR1249, Antineoplastic Agent, 03 medical and health sciences, 0302 clinical medicine, In vivo, Cancer stem cell, Cell Line, Tumor, Gene expression, microRNA, Drug Discovery, medicine, Humans, Hepatobiliary Malignancies, CRISPR-Cas System, Viability assay, Cell Proliferation, Cisplatin, Hepatology, Chemistry, Original Articles, Xenograft Model Antitumor Assays, Gemcitabine, High-Throughput Screening Assays, Gene Expression Regulation, Neoplastic, MicroRNAs, 030104 developmental biology, Biliary Tract Neoplasms, Biliary Tract Neoplasm, Cell culture, Drug Resistance, Neoplasm, Cancer research, 030211 gastroenterology & hepatology, Original Article, CRISPR-Cas Systems, Human, medicine.drug
Abstract

Background and Aims: Changes in single microRNA (miRNA) expression have been associated with chemo-resistance in biliary tract cancers (BTCs). However, a global assessment of the dynamic role of the microRNome has never been performed to identify potential therapeutic targets that are functionally relevant in the BTC cell response to chemotherapy. Approach and Results: High-throughput screening (HTS) of 997 locked nucleic acid miRNA inhibitors was performed in six cholangiocarcinoma cell lines treated with cisplatin and gemcitabine (CG) seeking changes in cell viability. Validation experiments were performed with mirVana probes. MicroRNA and gene expression was assessed by TaqMan assay, RNA-sequencing, and in situ hybridization in four independent cohorts of human BTCs. Knockout of microRNA was achieved by CRISPR-CAS9 in CCLP cells (MIR1249KO) and tested for effects on chemotherapy sensitivity in vitro and in vivo. HTS revealed that MIR1249 inhibition enhanced chemotherapy sensitivity across all cell lines. MIR1249 expression was increased in 41% of cases in human BTCs. In validation experiments, MIR1249 inhibition did not alter cell viability in untreated or dimethyl sulfoxide–treated cells; however, it did increase the CG effect. MIR1249 expression was increased in CD133+ biliary cancer cells freshly isolated from the stem cell niche of human BTCs as well as in CD133+ chemo-resistant CCLP cells. MIR1249 modulated the chemotherapy-induced enrichment of CD133+ cells by controlling their clonal expansion through the Wnt-regulator FZD8. MIR1249KO cells had impaired expansion of the CD133+ subclone and its enrichment after chemotherapy, reduced expression of cancer stem cell markers, and increased chemosensitivity. MIR1249KO xenograft BTC models showed tumor shrinkage after exposure to weekly CG, whereas wild-type models showed only stable disease over treatment. Conclusions: MIR1249 mediates resistance to CG in BTCs and may be tested as a target for therapeutics.

Published
2019
Full Text
View/download PDF

24. MIR21 drives resistance to Heat Shock Protein 90 inhibition in cholangiocarcinoma

Author

Lampis, Andrea, Carotenuto, Pietro, Vlachogiannis, Georgios, Cascione, Luciano, Hedayat, Somaieh, Burke, Rosemary, Clarke, Paul, Bosma, Else, Simbolo, Michele, Scarpa, Aldo, Yu, Sijia, Cole, Rebecca, Smyth, Elizabeth, Mateos, Javier Fernández, Begum, Ruwaida, Hezelova, Blanka, Eltahir, Zakaria, Wotherspoon, Andrew, Fotiadis, Nicos, Bali, Maria Antonietta, Nepal, Chirag, Khan, Khurum, Stubbs, Mark, Hahne, Jens C., Gasparini, Pierluigi, Guzzardo, Vincenza, Croce, Carlo M., Eccles, Suzanne, Fassan, Matteo, Cunningham, David, Andersen, Jesper B., Workman, Paul, Valeri, Nicola, Braconi, Chiara, Lampis, A., Carotenuto, P., Vlachogiannis, G., Cascione, L., Hedayat, S., Burke, R., Clarke, P., Bosma, E., Simbolo, M., Scarpa, A., Yu, S., Cole, R., Smyth, E., Mateos, J. F., Begum, R., Hezelova, B., Eltahir, Z., Wotherspoon, A., Fotiadis, N., Bali, M. A., Nepal, C., Khan, K., Stubbs, M., Hahne, J. C., Gasparini, P., Guzzardo, V., Croce, C. M., Eccles, S., Fassan, M., Cunningham, D., Andersen, J. B., Workman, P., Valeri, N., and Braconi, C.

Subjects
WT, wild type, Time Factors, Transcription Factor, Mice, SCID, DMSO, dimethyl sulfoxide, Antineoplastic Agent, Cholangiocarcinoma, Mice, Inbred NOD, AUY922, DNAJB5, bile duct cancer, organoid, miRNA, microRNA, PDO, patient-derived organoid, Tumor Cells, Cultured, Nuclear Protein, Nuclear Proteins, MicroRNA, HTS, high-throughput screen, Isocitrate Dehydrogenase, DNA-Binding Proteins, Organoids, FFPE, formalin-fixed paraffin-embedded, Gene Expression Regulation, Neoplastic, GI, growth inhibition, HSP, heat shock protein, Human, Signal Transduction, CCA, cholangiocarcinoma, FGFR, fibroblast growth factor receptor, Xenograft Model Antitumor Assay, Time Factor, Cell Survival, DNA-Binding Protein, Antineoplastic Agents, Transfection, Article, Cell Line, Tumor, Journal Article, Animals, Humans, HSP90 Heat-Shock Proteins, Bile Duct Neoplasm, Dose-Response Relationship, Drug, iCCA, intrahepatic cholantiocarcinoma, Animal, HSP40 Heat-Shock Proteins, Xenograft Model Antitumor Assays, MicroRNAs, HSP90 Heat-Shock Protein, Bile Duct Neoplasms, Drug Resistance, Neoplasm, Mutation, HSP40 Heat-Shock Protein, Transcription Factors
Abstract

Background & Aims: \ud Cholangiocarcinomas (CCA) are resistant to chemotherapy, so new therapeutic agents are needed. We performed a screen to identify small-molecule compounds that are active against CCAs. Levels of microRNA 21 (MIR21 or miRNA21) are increased in CCAs. We investigated whether miRNA21 mediates resistance of CCA cells and organoids to HSP90 inhibitors.\ud \ud Methods: \ud We performed a high-throughput screen of 484 small-molecule compounds to identify those that reduced viability of 6 human CCA cell lines. We tested the effects of HSP90 inhibitors on cells with disruption of the MIR21 gene, cells incubated with MIR21 inhibitors, and stable cell lines with inducible expression of MIR21. We obtained CCA biopsies from patients, cultured them as organoids (patient-derived organoids). We assessed their architecture, mutation and gene expression patterns, response to compounds in culture, and when grown as subcutaneous xenograft tumors in mice.\ud \ud Results: \ud Cells with IDH1 and PBRM1 mutations had the highest level of sensitivity to histone deacetylase inhibitors. HSP90 inhibitors were effective in all cell lines, irrespective of mutations. Sensitivity of cells to HSP90 inhibitors correlated inversely with baseline level of MIR21. Disruption of MIR21 increased cell sensitivity to HSP90 inhibitors. CCA cells that expressed transgenic MIR21 were more resistant to HSP90 inhibitors than cells transfected with control vectors; inactivation of MIR21 in these cells restored sensitivity to these agents. MIR21 was shown to target the DnaJ heat shock protein family (Hsp40) member B5 (DNAJB5). Transgenic expression of DNAJB5 in CCA cells that overexpressed MIR21 re-sensitized them to HSP90 inhibitors. Sensitivity of patient-derived organoids to HSP90 inhibitors, in culture and when grown as xenograft tumors in mice, depended on expression of miRNA21.\ud \ud Conclusions: \ud miRNA21 appears to mediate resistance of CCA cells to HSP90 inhibitors by reducing levels of DNAJB5. HSP90 inhibitors might be developed for the treatment of CCA and miRNA21 might be a marker of sensitivity to these agents.

Published
2018
Full Text
View/download PDF

25. Circulating tumor DNA dynamics and clinical outcome in metastatic colorectal cancer patients undergoing front-line chemotherapy.

Author

Ghidini M, Hahne JC, Senti C, Heide T, Proszek PZ, Shaikh R, Carter P, Hubank M, Trevisani F, Garrone O, Cappelletti MR, Generali D, Cattaneo M, Gnocchi N, Donati G, Gobbi A, Grizzi G, Lampis A, Elghadi R, Tanzi G, Tomasello G, Ratti M, Pinato DJ, Fassan M, Vlachogiannis G, Sottoriva A, Passalacqua R, and Valeri N

Abstract

Purpose: we tested whether ctDNA changes may be used to assess early response and clinical outcome in metastatic colorectal cancer (mCRC) patients undergoing front-line systemic anti-cancer therapy (SACT)., Experimental Design: 862 plasma samples were collected 4-weekly from baseline (BL) until disease progression in mCRC patients receiving front line SACT. ctDNA normalization was defined as ≥99% clearance after 1 month of therapy (Mo1) in the 3 variants with the highest allele frequency in BL ctDNA., Results: 83 paired samples from 75 patients were available for analysis. 12 pairs (14.4%) showed no variants in either BL or Mo1. In the remaining 71 comparisons (65 patients), 37 (52.1%) showed ctDNA normalization at Mo1. Patients that cleared ctDNA had significantly longer overall (45.6 months) and progression-free survival (13.9 months) compared to non-normalized patients [OS= 22.6 months (Log-rank p = 0.01) and PFS= 10.7 months (Log-rank p = 0.036) respectively]. In addition, higher response rate was observed in patients with ctDNA clearance (72.9%) compared to non-normalized cases (38.2%). Longitudinal sequencing of at least four timepoints in pts with a PFS>10 months showed emerging variants in 47.8% of cases; in all these patients the trajectory of these new "outlier" variants appeared in stark contrast with the clinical-radiological course of disease and the trend in other mutations., Conclusions: ctDNA clearance represents an early indicator of benefit from SACT in mCRC patients; serial tracking of multiple variants is warranted to improve specificity and to avoid misleading information due to the emergence of mutations of unknown clinical significance.

Published
2024
Full Text
View/download PDF

26. Circulating microRNA Analysis in a Prospective Co-clinical Trial Identifies MIR652-3p as a Response Biomarker and Driver of Regorafenib Resistance Mechanisms in Colorectal Cancer.

Author

Hedayat S, Cascione L, Cunningham D, Schirripa M, Lampis A, Hahne JC, Tunariu N, Hong SP, Marchetti S, Khan K, Fontana E, Angerilli V, Delrieux M, Nava Rodrigues D, Procaccio L, Rao S, Watkins D, Starling N, Chau I, Braconi C, Fotiadis N, Begum R, Guppy N, Howell L, Valenti M, Cribbes S, Kolozsvari B, Kirkin V, Lonardi S, Ghidini M, Passalacqua R, Elghadi R, Magnani L, Pinato DJ, Di Maggio F, Ghelardi F, Sottotetti E, Vetere G, Ciracì P, Vlachogiannis G, Pietrantonio F, Cremolini C, Cortellini A, Loupakis F, Fassan M, and Valeri N

Subjects
Humans, Animals, Female, Prospective Studies, Male, Mice, Xenograft Model Antitumor Assays, Gene Expression Regulation, Neoplastic drug effects, Aged, Liquid Biopsy methods, Middle Aged, Cell Line, Tumor, MicroRNAs genetics, MicroRNAs blood, Colorectal Neoplasms drug therapy, Colorectal Neoplasms genetics, Colorectal Neoplasms pathology, Colorectal Neoplasms blood, Phenylurea Compounds pharmacology, Phenylurea Compounds therapeutic use, Pyridines therapeutic use, Pyridines pharmacology, Drug Resistance, Neoplasm genetics, Biomarkers, Tumor genetics, Biomarkers, Tumor blood, Circulating MicroRNA
Abstract

Purpose: The multi-kinase inhibitor (mKi) regorafenib has demonstrated efficacy in chemorefractory patients with metastatic colorectal cancer (mCRC). However, lack of predictive biomarkers and concerns over significant toxicities hamper the use of regorafenib in clinical practice., Experimental Design: Serial liquid biopsies were obtained at baseline and monthly until disease progression in chemorefractory patients with mCRC treated with regorafenib in a phase II clinical trial (PROSPECT-R n = 40; NCT03010722) and in a multicentric validation cohort (n = 241). Tissue biopsies collected at baseline, after 2 months and at progression in the PROSPECT-R trial were used to establish patient-derived organoids (PDO) and for molecular analyses. MicroRNA profiling was performed on baseline bloods using the NanoString nCounter platform and results were validated by digital-droplet PCR and/or ISH in paired liquid and tissue biopsies. PDOs co-cultures and PDO-xenotransplants were generated for functional analyses., Results: Large-scale microRNA expression analysis in longitudinal matched liquid and tissue biopsies from the PROSPECT-R trial identified MIR652-3p as a biomarker of clinical benefit to regorafenib. These findings were confirmed in an independent validation cohort and in a "control" group of 100 patients treated with lonsurf. Using ex vivo co-culture assays paired with single-cell RNA-sequencing of PDO established pre- and post-treatment, we modeled regorafenib response observed in vivo and in patients, and showed that MIR652-3p controls resistance to regorafenib by impairing regorafenib-induced lethal autophagy and by orchestrating the switch from neo-angiogenesis to vessel co-option., Conclusions: Our results identify MIR652-3p as a potential biomarker and as a driver of cell and non-cell-autonomous mechanisms of resistance to regorafenib., (©2024 American Association for Cancer Research.)

Published
2024
Full Text
View/download PDF

27. MicroRNAs as biomarkers for trastuzumab-based therapy in HER2-positive advanced oesophago-gastric cancer patients.

Author

Lote H, Mousoullou F, Vlachogiannis G, Lampis A, Satchwell L, Peckitt C, Fong C, Begum R, Kidd S, Cromarty S, Gordon A, Fribbens C, Rao S, Starling N, Chau I, Cunningham D, and Valeri N

Abstract

Background: This study aimed to identify microRNAs (miRs) as circulating biomarkers of resistance to first-line trastuzumab-based therapy in advanced HER2-positive oesophago-gastric cancer patients., Methods: A high-throughput 1015 Exiqon miRCURY LNA™ microRNA inhibitor library screen was performed in trastuzumab-treated HER2-positive NCI-N87 and HER2-negative FLO-1 oesophago-gastric cancer cell lines. NanoString nCounter ® miR analysis was performed in NCI-N87, FLO-1, and MAGIC trial (ISRCTN93793971) formalin-fixed paraffin-embedded (FFPE) oesophago-gastric cancer patient samples. MiR-148a-3p copies in plasma samples were quantified using digital droplet polymerase chain reaction (ddPCR) from HER2-positive oesophago-gastric cancer patients treated with standard-of-care trastuzumab-based therapy within the FOrMAT (NCT02112357) and PLATFORM (NCT02678182) clinical trials. The primary endpoints were overall survival (OS) for plasma miR-148a-3p HIGH (>median) versus LOW (≤median). The secondary endpoints were progression-free survival (PFS) and 3-month progression-free rates (PFRs) miR-148a-3p HIGH versus LOW. PLATFORM sensitivity analysis normalised miR-148a-3p (NmiR-148a-3p)., Results: The inhibition of miR-148a-3p reduced NCI-N87 relative cell viability (<0.6) and expression was high (>242) in NCI-N87 and HER2-positive MAGIC trial patients (n=5). Normalised-miR-148a-3p (NmiR-148a-3p) LOW versus HIGH demonstrated a statistically significant difference in 3-month PFRs (n=23; OR, 0.11 [0.02-0.78]; p=0.027; aOR, 0.03 [0.001-0.71], p=0.029) but no difference in OS or PFS. There was no statistically significant relationship between miR-148-3p LOW versus HIGH for OS (PLATFORM, n=62; hazard ratio [HR], 0.98 [0.57-1.66]; p=0.933; FOrMAT, n=8; HR, 0.54 [0.13-2.31]; p=0.322), PFS (n=62; HR, 1.08 [0.65-1.81]; p=0.759; FOrMAT, n=8; HR, 1.26 [0.31-5.07]; p=0.714), or PFRs (PLATFORM, n=31; odds ratio [OR], 0.67 [0.2-2.8]; p=0.577)., Conclusion: Normalised miR-148a-3p may be a relevant biomarker for trastuzumab-based therapy in advanced HER2-positive oesophago-gastric cancer patients., Competing Interests: CFo has received honoraria from Bristol-Myers Squibb. SK and SC have received research funding to their Research Institution from AstraZeneca, Clovis Oncology, and Lilly. SR has a consulting or advisory role at Bayer and Roche and has received travel, accommodation, and expenses from Bayer, Incyte, and Servier. IC has received honoraria from Eisai, Lilly, Roche/Genentech, and Servier and has a consulting or advisory role at Astellas Pharma, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Incyte, Lilly, Merck Serono, MSD Oncology, OncXerna Therapeutics, Roche/Genentech, Seagen Servier, Sotio, Taiho Oncology, and Terning Point Therapeutics. Additionally, IC has received research funding to the Research Institution from Janseen-Cilag and Lilly. NS has received honoraria from Amgen, GlaxoSmithKline, Lilly, Merck Serono, MSD Oncology, Novartis, Pierre Fabre, Seagen, and Servier; has a consulting or advisory role at AstraZeneca, MSD Oncology, Novartis Pharmaceuticals Uk Ltd, and Pfizer; has received research funding to the institution from AstraZeneca, BMS, Pfizer, and EMD Serono; has received travel accommodations or expenses from Guardant Health and MSD Oncology; and has uncompensated relationships with Guardant Health. DC holds stock and other ownership interests in OVIBIO and a consulting or advisory role at OVIBIO; and has received research funding to the institution from 4SC, Bayer, Celgene, Clovis Oncology, Leap Oncology, Lilly, MedImmune, and Roche. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lote, Mousoullou, Vlachogiannis, Lampis, Satchwell, Peckitt, Fong, Begum, Kidd, Cromarty, Gordon, Fribbens, Rao, Starling, Chau, Cunningham and Valeri.)

Published
2023
Full Text
View/download PDF

28. USP7 inactivation suppresses APC-mutant intestinal hyperproliferation and tumor development.

Author

Novellasdemunt L, Kucharska A, Baulies A, Hutton C, Vlachogiannis G, Repana D, Rowan A, Suárez-Bonnet A, Ciccarelli F, Valeri N, and Li VSW

Subjects
Humans, Mice, Animals, Ubiquitin-Specific Peptidase 7 genetics, Ubiquitin-Specific Peptidase 7 metabolism, Carcinogenesis genetics, Cell Transformation, Neoplastic genetics, Wnt Signaling Pathway, beta Catenin genetics, beta Catenin metabolism, Colorectal Neoplasms drug therapy, Colorectal Neoplasms genetics, Colorectal Neoplasms pathology, Adenomatous Polyposis Coli genetics
Abstract

Adenomatous polyposis coli (APC) mutation is the hallmark of colorectal cancer (CRC), resulting in constitutive WNT activation. Despite decades of research, targeting WNT signaling in cancer remains challenging due to its on-target toxicity. We have previously shown that the deubiquitinating enzyme USP7 is a tumor-specific WNT activator in APC-truncated cells by deubiquitinating and stabilizing β-catenin, but its role in gut tumorigenesis is unknown. Here, we show in vivo that deletion of Usp7 in Apc-truncated mice inhibits crypt hyperproliferation and intestinal tumor development. Loss of Usp7 prolongs the survival of the sporadic intestinal tumor model. Genetic deletion, but not pharmacological inhibition, of Usp7 in Apc +/- intestine induces colitis and enteritis. USP7 inhibitor treatment suppresses growth of patient-derived cancer organoids carrying APC truncations in vitro and in xenografts. Our findings provide direct evidence that USP7 inhibition may offer a safe and efficacious tumor-specific therapy for both sporadic and germline APC-mutated CRC., Competing Interests: Conflict of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Published
2023
Full Text
View/download PDF

29. New molecular mechanisms in cholangiocarcinoma: signals triggering interleukin-6 production in tumor cells and KRAS co-opted epigenetic mediators driving metabolic reprogramming.

Author

Colyn L, Alvarez-Sola G, Latasa MU, Uriarte I, Herranz JM, Arechederra M, Vlachogiannis G, Rae C, Pineda-Lucena A, Casadei-Gardini A, Pedica F, Aldrighetti L, López-López A, López-Gonzálvez A, Barbas C, Ciordia S, Van Liempd SM, Falcón-Pérez JM, Urman J, Sangro B, Vicent S, Iraburu MJ, Prosper F, Nelson LJ, Banales JM, Martinez-Chantar ML, Marin JJG, Braconi C, Trautwein C, Corrales FJ, Cubero FJ, Berasain C, Fernandez-Barrena MG, and Avila MA

Subjects
Animals, Arachnodactyly, Bile Ducts, Intrahepatic metabolism, Bile Ducts, Intrahepatic pathology, Carcinogenesis genetics, Contracture, Epigenesis, Genetic, ErbB Receptors genetics, ErbB Receptors metabolism, Glucose, Glycine metabolism, Humans, Interleukin-6 genetics, Interleukin-6 metabolism, Mice, Phosphoglycerate Dehydrogenase genetics, Proteomics, Proto-Oncogene Proteins p21(ras) genetics, Proto-Oncogene Proteins p21(ras) metabolism, Rats, Serine metabolism, Bile Duct Neoplasms genetics, Bile Duct Neoplasms pathology, Cholangiocarcinoma pathology
Abstract

Background: Cholangiocarcinoma (CCA) is still a deadly tumour. Histological and molecular aspects of thioacetamide (TAA)-induced intrahepatic CCA (iCCA) in rats mimic those of human iCCA. Carcinogenic changes and therapeutic vulnerabilities in CCA may be captured by molecular investigations in bile, where we performed bile proteomic and metabolomic analyses that help discovery yet unknown pathways relevant to human iCCA., Methods: Cholangiocarcinogenesis was induced in rats (TAA) and mice (Jnk Δhepa  + CCl 4  + DEN model). We performed proteomic and metabolomic analyses in bile from control and CCA-bearing rats. Differential expression was validated in rat and human CCAs. Mechanisms were addressed in human CCA cells, including Huh28-KRAS G12D cells. Cell signaling, growth, gene regulation and [U- 13 C]-D-glucose-serine fluxomics analyses were performed. In vivo studies were performed in the clinically-relevant iCCA mouse model., Results: Pathways related to inflammation, oxidative stress and glucose metabolism were identified by proteomic analysis. Oxidative stress and high amounts of the oncogenesis-supporting amino acids serine and glycine were discovered by metabolomic studies. Most relevant hits were confirmed in rat and human CCAs (TCGA). Activation of interleukin-6 (IL6) and epidermal growth factor receptor (EGFR) pathways, and key genes in cancer-related glucose metabolic reprogramming, were validated in TAA-CCAs. In TAA-CCAs, G9a, an epigenetic pro-tumorigenic writer, was also increased. We show that EGFR signaling and mutant KRAS G12D can both activate IL6 production in CCA cells. Furthermore, phosphoglycerate dehydrogenase (PHGDH), the rate-limiting enzyme in serine-glycine pathway, was upregulated in human iCCA correlating with G9a expression. In a G9a activity-dependent manner, KRAS G12D promoted PHGDH expression, glucose flow towards serine synthesis, and increased CCA cell viability. KRAS G12D CAA cells were more sensitive to PHGDH and G9a inhibition than controls. In mouse iCCA, G9a pharmacological targeting reduced PHGDH expression., Conclusions: In CCA, we identified new pro-tumorigenic mechanisms: Activation of EGFR signaling or KRAS mutation drives IL6 expression in tumour cells; Glucose metabolism reprogramming in iCCA includes activation of the serine-glycine pathway; Mutant KRAS drives PHGDH expression in a G9a-dependent manner; PHGDH and G9a emerge as therapeutic targets in iCCA., (© 2022. The Author(s).)

Published
2022
Full Text
View/download PDF

30. MIR21-induced loss of junctional adhesion molecule A promotes activation of oncogenic pathways, progression and metastasis in colorectal cancer.

Author

Lampis A, Hahne JC, Gasparini P, Cascione L, Hedayat S, Vlachogiannis G, Murgia C, Fontana E, Edwards J, Horgan PG, Terracciano L, Sansom OJ, Martins CD, Kramer-Marek G, Croce CM, Braconi C, Fassan M, and Valeri N

Subjects
Animals, Case-Control Studies, Cell Adhesion Molecules deficiency, Cell Adhesion Molecules genetics, Cell Line, Tumor, Cell Proliferation physiology, Colorectal Neoplasms genetics, Colorectal Neoplasms pathology, Disease Progression, Female, Heterografts, Humans, Mice, Mice, Inbred NOD, Mice, Nude, Mice, SCID, Neoplasm Metastasis, Receptors, Cell Surface deficiency, Receptors, Cell Surface genetics, Cell Adhesion Molecules metabolism, Colorectal Neoplasms metabolism, MicroRNAs metabolism, Receptors, Cell Surface metabolism
Abstract

Junctional adhesion molecules (JAMs) play a critical role in cell permeability, polarity and migration. JAM-A, a key protein of the JAM family, is altered in a number of conditions including cancer; however, consequences of JAM-A dysregulation on carcinogenesis appear to be tissue dependent and organ dependent with significant implications for the use of JAM-A as a biomarker or therapeutic target. Here, we test the expression and prognostic role of JAM-A downregulation in primary and metastatic colorectal cancer (CRC) (n = 947). We show that JAM-A downregulation is observed in ~60% of CRC and correlates with poor outcome in four cohorts of stages II and III CRC (n = 1098). Using JAM-A knockdown, re-expression and rescue experiments in cell line monolayers, 3D spheroids, patient-derived organoids and xenotransplants, we demonstrate that JAM-A silencing promotes proliferation and migration in 2D and 3D cell models and increases tumour volume and metastases in vivo. Using gene-expression and proteomic analyses, we show that JAM-A downregulation results in the activation of ERK, AKT and ROCK pathways and leads to decreased bone morphogenetic protein 7 expression. We identify MIR21 upregulation as the cause of JAM-A downregulation and show that JAM-A rescue mitigates the effects of MIR21 overexpression on cancer phenotype. Our results identify a novel molecular loop involving MIR21 dysregulation, JAM-A silencing and activation of multiple oncogenic pathways in promoting invasiveness and metastasis in CRC., (© 2021. The Author(s).)

Published
2021
Full Text
View/download PDF

31. A phospho-proteomic study of cetuximab resistance in KRAS/NRAS/BRAF V600 wild-type colorectal cancer.

Author

Georgiou A, Stewart A, Vlachogiannis G, Pickard L, Valeri N, Cunningham D, Whittaker SR, and Banerji U

Subjects
Adult, Aged, Antineoplastic Agents, Immunological pharmacology, Caco-2 Cells, Cell Line, Tumor, Colorectal Neoplasms pathology, Humans, Middle Aged, Phosphatidylinositol 3-Kinases metabolism, Signal Transduction drug effects, Cetuximab pharmacology, Colorectal Neoplasms metabolism, Drug Resistance, Neoplasm drug effects, GTP Phosphohydrolases metabolism, Membrane Proteins metabolism, Phosphoproteins metabolism, Proteomics methods, Proto-Oncogene Proteins B-raf metabolism, Proto-Oncogene Proteins p21(ras) metabolism
Abstract

Purpose: We hypothesised that plasticity in signal transduction may be a mechanism of drug resistance and tested this hypothesis in the setting of cetuximab resistance in patients with KRAS/NRAS/BRAF V600 wild-type colorectal cancer (CRC)., Methods: A multiplex antibody-based platform was used to study simultaneous changes in signal transduction of 55 phospho-proteins in 12 KRAS/NRAS/BRAF V600 wild-type CRC cell lines (6 cetuximab sensitive versus 6 cetuximab resistant) following 1 and 4 h in vitro cetuximab exposure. We validated our results in CRC patient samples (n = 4) using ex vivo exposure to cetuximab in KRAS/NRAS/BRAF V600 cells that were immunomagnetically separated from the serous effusions of patients with known cetuximab resistance., Results: Differences in levels of phospho-proteins in cetuximab sensitive and resistant cell lines included reductions in phospho-RPS6 and phospho-PRAS40 in cetuximab sensitive, but not cetuximab resistant cell lines at 1 and 4 h, respectively. In addition, phospho-AKT levels were found to be elevated in 3/4 patient samples following ex vivo incubation with cetuximab for 1 h. We further explored these findings by studying the effects of combinations of cetuximab and two PI3K pathway inhibitors in 3 cetuximab resistant cell lines. The addition of PI3K pathway inhibitors to cetuximab led to a significantly higher reduction in colony formation capacity compared to cetuximab alone., Conclusion: Our findings suggest activation of the PI3K pathway as a mechanism of cetuximab resistance in KRAS/NRAS/BRAF V600 wild-type CRC., (© 2021. Crown.)

Published
2021
Full Text
View/download PDF

32. EGFR amplification and outcome in a randomised phase III trial of chemotherapy alone or chemotherapy plus panitumumab for advanced gastro-oesophageal cancers.

Author

Smyth EC, Vlachogiannis G, Hedayat S, Harbery A, Hulkki-Wilson S, Salati M, Kouvelakis K, Fernandez-Mateos J, Cresswell GD, Fontana E, Seidlitz T, Peckitt C, Hahne JC, Lampis A, Begum R, Watkins D, Rao S, Starling N, Waddell T, Okines A, Crosby T, Mansoor W, Wadsley J, Middleton G, Fassan M, Wotherspoon A, Braconi C, Chau I, Vivanco I, Sottoriva A, Stange DE, Cunningham D, and Valeri N

Subjects
Adenocarcinoma chemistry, Aged, Antibiotics, Antineoplastic administration & dosage, Antineoplastic Agents, Immunological administration & dosage, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor analysis, Epirubicin administration & dosage, ErbB Receptors analysis, Esophageal Neoplasms chemistry, Humans, Male, Middle Aged, Panitumumab administration & dosage, Stomach Neoplasms chemistry, Adenocarcinoma drug therapy, Antibiotics, Antineoplastic therapeutic use, Antineoplastic Agents, Immunological therapeutic use, Epirubicin therapeutic use, ErbB Receptors antagonists & inhibitors, Esophageal Neoplasms drug therapy, Panitumumab therapeutic use, Stomach Neoplasms drug therapy
Abstract

Objective: Epidermal growth factor receptor (EGFR) inhibition may be effective in biomarker-selected populations of advanced gastro-oesophageal adenocarcinoma (aGEA) patients. Here, we tested the association between outcome and EGFR copy number (CN) in pretreatment tissue and plasma cell-free DNA (cfDNA) of patients enrolled in a randomised first-line phase III clinical trial of chemotherapy or chemotherapy plus the anti-EGFR monoclonal antibody panitumumab in aGEA (NCT00824785)., Design: EGFR CN by either fluorescence in situ hybridisation (n=114) or digital-droplet PCR in tissues (n=250) and plasma cfDNAs (n=354) was available for 474 (86%) patients in the intention-to-treat (ITT) population. Tissue and plasma low-pass whole-genome sequencing was used to screen for coamplifications in receptor tyrosine kinases. Interaction between chemotherapy and EGFR inhibitors was modelled in patient-derived organoids (PDOs) from aGEA patients., Results: EGFR amplification in cfDNA correlated with poor survival in the ITT population and similar trends were observed when the analysis was conducted in tissue and plasma by treatment arm. EGFR inhibition in combination with chemotherapy did not correlate with improved survival, even in patients with significant EGFR CN gains. Addition of anti-EGFR inhibitors to the chemotherapy agent epirubicin in PDOs, resulted in a paradoxical increase in viability and accelerated progression through the cell cycle, associated with p21 and cyclin B1 downregulation and cyclin E1 upregulation, selectively in organoids from EGFR -amplified aGEA., Conclusion: EGFR CN can be accurately measured in tissue and liquid biopsies and may be used for the selection of aGEA patients. EGFR inhibitors may antagonise the antitumour effect of anthracyclines with important implications for the design of future combinatorial trials., Competing Interests: Competing interests: ES declares honoraria for advisory role from Astellas, BMS, Celgene, Five Prime, Gritstone Oncology, and Servier. DW has received honoraria from Amgen. NS received research funding from AstraZeneca, Pfizer, BMS and honoraria from Servier, MSD, Merck Serono and AstraZeneca. JW received honoraria from Eisai, AstraZeneca, Sanofi-Genzyme, Ipsen, Novartis, Bayer, Celgene and Advanced Accelerator Applications. IC has had advisory roles with Merck Serono, Roche, Sanofi Oncology, Bristol Myers Squibb, Eli-Lilly, Novartis, Gilead Science. He has received research funding from Merck-Serono, Novartis, Roche and Sanofi Oncology, and honoraria from Roche, Sanofi-Oncology, Eli-Lilly, Taiho, Bayer and Prime Therapeutics. IV has received honoraria from AbbVie. He has received researched funding from Genmab and Basilea. DC received research funding from 4SC, AstraZeneca, Bayer, Celgene, Clovis, Eli Lilly, Janssen, Medimmune, Merck, Merrimack, Amgen, Sanofi. NV received honoraria from Merck Serono, Pfizer, Bayer and Eli-Lilly. All other authors declare no conflict of interest., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Published
2021
Full Text
View/download PDF

33. MNK Inhibition Sensitizes KRAS -Mutant Colorectal Cancer to mTORC1 Inhibition by Reducing eIF4E Phosphorylation and c-MYC Expression.

Author

Knight JRP, Alexandrou C, Skalka GL, Vlahov N, Pennel K, Officer L, Teodosio A, Kanellos G, Gay DM, May-Wilson S, Smith EM, Najumudeen AK, Gilroy K, Ridgway RA, Flanagan DJ, Smith RCL, McDonald L, MacKay C, Cheasty A, McArthur K, Stanway E, Leach JD, Jackstadt R, Waldron JA, Campbell AD, Vlachogiannis G, Valeri N, Haigis KM, Sonenberg N, Proud CG, Jones NP, Swarbrick ME, McKinnon HJ, Faller WJ, Le Quesne J, Edwards J, Willis AE, Bushell M, and Sansom OJ

Subjects
Animals, Colorectal Neoplasms metabolism, Disease Models, Animal, Eukaryotic Initiation Factor-4E metabolism, Humans, Intracellular Signaling Peptides and Proteins metabolism, Mice, Mice, Inbred C57BL, Phosphorylation, Protein Serine-Threonine Kinases metabolism, Colorectal Neoplasms genetics, Eukaryotic Initiation Factor-4E drug effects, Intracellular Signaling Peptides and Proteins drug effects, MTOR Inhibitors pharmacology, Protein Serine-Threonine Kinases drug effects
Abstract

KRAS -mutant colorectal cancers are resistant to therapeutics, presenting a significant problem for ∼40% of cases. Rapalogs, which inhibit mTORC1 and thus protein synthesis, are significantly less potent in KRAS -mutant colorectal cancer. Using Kras -mutant mouse models and mouse- and patient-derived organoids, we demonstrate that KRAS with G12D mutation fundamentally rewires translation to increase both bulk and mRNA-specific translation initiation. This occurs via the MNK/eIF4E pathway culminating in sustained expression of c-MYC. By genetic and small-molecule targeting of this pathway, we acutely sensitize KRAS G12D models to rapamycin via suppression of c-MYC. We show that 45% of colorectal cancers have high signaling through mTORC1 and the MNKs, with this signature correlating with a 3.5-year shorter cancer-specific survival in a subset of patients. This work provides a c-MYC-dependent cotargeting strategy with remarkable potency in multiple Kras -mutant mouse models and metastatic human organoids and identifies a patient population that may benefit from its clinical application. SIGNIFICANCE: KRAS mutation and elevated c-MYC are widespread in many tumors but remain predominantly untargetable. We find that mutant KRAS modulates translation, culminating in increased expression of c-MYC. We describe an effective strategy targeting mTORC1 and MNK in KRAS -mutant mouse and human models, pathways that are also commonly co-upregulated in colorectal cancer. This article is highlighted in the In This Issue feature, p. 995 ., (©2020 American Association for Cancer Research.)

Published
2021
Full Text
View/download PDF

34. Serine synthesis pathway inhibition cooperates with dietary serine and glycine limitation for cancer therapy.

Author

Tajan M, Hennequart M, Cheung EC, Zani F, Hock AK, Legrave N, Maddocks ODK, Ridgway RA, Athineos D, Suárez-Bonnet A, Ludwig RL, Novellasdemunt L, Angelis N, Li VSW, Vlachogiannis G, Valeri N, Mainolfi N, Suri V, Friedman A, Manfredi M, Blyth K, Sansom OJ, and Vousden KH

Subjects
Activating Transcription Factor 4 genetics, Activating Transcription Factor 4 metabolism, Animals, Cell Line, Tumor, Cell Proliferation, Female, Glycine analysis, Humans, Male, Mice, Mice, Inbred C57BL, Neoplasms enzymology, Neoplasms metabolism, Neoplasms physiopathology, Phosphoglycerate Dehydrogenase metabolism, Serine analysis, Glycine metabolism, Neoplasms diet therapy, Serine biosynthesis
Abstract

Many tumour cells show dependence on exogenous serine and dietary serine and glycine starvation can inhibit the growth of these cancers and extend survival in mice. However, numerous mechanisms promote resistance to this therapeutic approach, including enhanced expression of the de novo serine synthesis pathway (SSP) enzymes or activation of oncogenes that drive enhanced serine synthesis. Here we show that inhibition of PHGDH, the first step in the SSP, cooperates with serine and glycine depletion to inhibit one-carbon metabolism and cancer growth. In vitro, inhibition of PHGDH combined with serine starvation leads to a defect in global protein synthesis, which blocks the activation of an ATF-4 response and more broadly impacts the protective stress response to amino acid depletion. In vivo, the combination of diet and inhibitor shows therapeutic efficacy against tumours that are resistant to diet or drug alone, with evidence of reduced one-carbon availability. However, the defect in ATF4-response seen in vitro following complete depletion of available serine is not seen in mice, where dietary serine and glycine depletion and treatment with the PHGDH inhibitor lower but do not eliminate serine. Our results indicate that inhibition of PHGDH will augment the therapeutic efficacy of a serine depleted diet.

Published
2021
Full Text
View/download PDF

35. A MYC-GCN2-eIF2α negative feedback loop limits protein synthesis to prevent MYC-dependent apoptosis in colorectal cancer.

Author

Schmidt S, Gay D, Uthe FW, Denk S, Paauwe M, Matthes N, Diefenbacher ME, Bryson S, Warrander FC, Erhard F, Ade CP, Baluapuri A, Walz S, Jackstadt R, Ford C, Vlachogiannis G, Valeri N, Otto C, Schülein-Völk C, Maurus K, Schmitz W, Knight JRP, Wolf E, Strathdee D, Schulze A, Germer CT, Rosenwald A, Sansom OJ, Eilers M, and Wiegering A

Subjects
Adenomatous Polyposis Coli Protein genetics, Adenomatous Polyposis Coli Protein metabolism, Animals, Apoptosis genetics, Cell Line, Tumor, Cell Movement, Cell Proliferation, Colon metabolism, Colon pathology, Colorectal Neoplasms metabolism, Colorectal Neoplasms mortality, Colorectal Neoplasms pathology, Eukaryotic Initiation Factor-2 metabolism, Eukaryotic Initiation Factor-2B antagonists & inhibitors, Eukaryotic Initiation Factor-2B genetics, Eukaryotic Initiation Factor-2B metabolism, Feedback, Physiological, Female, HCT116 Cells, HEK293 Cells, Humans, Male, Mice, Mice, Inbred C57BL, Protein Biosynthesis, Protein Serine-Threonine Kinases metabolism, Proto-Oncogene Proteins c-myc metabolism, Signal Transduction, Survival Analysis, Xenograft Model Antitumor Assays, Colorectal Neoplasms genetics, Eukaryotic Initiation Factor-2 genetics, Gene Expression Regulation, Neoplastic, Protein Serine-Threonine Kinases genetics, Proto-Oncogene Proteins c-myc genetics
Abstract

Tumours depend on altered rates of protein synthesis for growth and survival, which suggests that mechanisms controlling mRNA translation may be exploitable for therapy. Here, we show that loss of APC, which occurs almost universally in colorectal tumours, strongly enhances the dependence on the translation initiation factor eIF2B5. Depletion of eIF2B5 induces an integrated stress response and enhances translation of MYC via an internal ribosomal entry site. This perturbs cellular amino acid and nucleotide pools, strains energy resources and causes MYC-dependent apoptosis. eIF2B5 limits MYC expression and prevents apoptosis in APC-deficient murine and patient-derived organoids and in APC-deficient murine intestinal epithelia in vivo. Conversely, the high MYC levels present in APC-deficient cells induce phosphorylation of eIF2α via the kinases GCN2 and PKR. Pharmacological inhibition of GCN2 phenocopies eIF2B5 depletion and has therapeutic efficacy in tumour organoids, which demonstrates that a negative MYC-eIF2α feedback loop constitutes a targetable vulnerability of colorectal tumours.

Published
2019
Full Text
View/download PDF

36. miR-31-3p Expression and Benefit from Anti-EGFR Inhibitors in Metastatic Colorectal Cancer Patients Enrolled in the Prospective Phase II PROSPECT-C Trial.

Author

Anandappa G, Lampis A, Cunningham D, Khan KH, Kouvelakis K, Vlachogiannis G, Hedayat S, Tunariu N, Rao S, Watkins D, Starling N, Braconi C, Darvish-Damavandi M, Lote H, Thomas J, Peckitt C, Kalaitzaki R, Khan N, Fotiadis N, Rugge M, Begum R, Rana I, Bryant A, Hahne JC, Chau I, Fassan M, and Valeri N

Subjects
Aged, Antineoplastic Agents, Immunological administration & dosage, Antineoplastic Agents, Immunological adverse effects, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, Colorectal Neoplasms diagnosis, Colorectal Neoplasms mortality, ErbB Receptors antagonists & inhibitors, ErbB Receptors metabolism, Female, Humans, Immunohistochemistry, In Situ Hybridization, Male, Middle Aged, Molecular Targeted Therapy, Prognosis, Retreatment, Tomography, X-Ray Computed, Treatment Outcome, Antineoplastic Agents, Immunological therapeutic use, Colorectal Neoplasms drug therapy, Colorectal Neoplasms genetics, Gene Expression, MicroRNAs genetics
Abstract

Purpose: Anti-EGFR mAbs are effective in the treatment of metastatic colorectal cancer (mCRC) patients. RAS status and tumor location (sidedness) are predictive markers of patients' response to anti-EGFR mAbs. Recently, low miR-31-3p expression levels have been correlated with clinical benefit from the anti-EGFR mAb cetuximab. Here, we aimed to validate the predictive power of miR-31-3p in a prospective cohort of chemorefractory mCRC patients treated with single-agent anti-EGFR mAbs., Experimental Design: miR-31-3p was tested by in situ hybridization (ISH) in 91 pretreatment core biopsies from metastatic deposits of 45 patients with mCRC. Sequential tissue biopsies obtained before treatment, at the time of partial response, and at disease progression were tested to monitor changes in miR-31-3p expression overtreatment. miR-31-3p expression, sidedness, and RAS status in pretreatment cell-free DNA were combined in multivariable regression models to assess the predictive value of each variable alone or in combination., Results: Patients with low miR-31-3p expression in pretreatment biopsies showed better overall response rate, as well as better progression-free survival and overall survival, compared to those with high miR-31-3p expression. The prognostic effect of miR-31-3p was independent from age, gender, and sidedness. No significant changes in the expression of miR-31-3p were observed when sequential tissue biopsies were tested in long-term or poor responders to anti-EGFR mAbs. miR-31-3p scores were similar when pretreatment biopsies were compared with treatment-naïve archival tissues (often primary colorectal cancer)., Conclusions: Our study validates the role of miR-31-3p as potential predictive biomarker of selection for anti-EGFR mAbs., (©2019 American Association for Cancer Research.)

Published
2019
Full Text
View/download PDF

37. Correction: Suppression of interferon gene expression overcomes resistance to MEK inhibition in KRAS-mutant colorectal cancer.

Author

Wagner S, Vlachogiannis G, De Haven Brandon A, Valenti M, Box G, Jenkins L, Mancusi C, Self A, Manodoro F, Assiotis I, Robinson P, Chauhan R, Rust AG, Matthews N, Eason K, Khan K, Starling N, Cunningham D, Sadanandam A, Isacke CM, Kirkin V, Valeri N, and Whittaker SR

Abstract

A correction to this paper has been published and can be accessed via a link at the top of the paper.

Published
2019
Full Text
View/download PDF

38. Suppression of interferon gene expression overcomes resistance to MEK inhibition in KRAS-mutant colorectal cancer.

Author

Wagner S, Vlachogiannis G, De Haven Brandon A, Valenti M, Box G, Jenkins L, Mancusi C, Self A, Manodoro F, Assiotis I, Robinson P, Chauhan R, Rust AG, Matthews N, Eason K, Khan K, Starling N, Cunningham D, Sadanandam A, Isacke CM, Kirkin V, Valeri N, and Whittaker SR

Subjects
Animals, Azepines pharmacology, Cell Line, Tumor, Colorectal Neoplasms genetics, Colorectal Neoplasms metabolism, Drug Synergism, Female, Gene Expression Regulation, Neoplastic drug effects, Humans, Mice, Mutation, Organoids drug effects, Proto-Oncogene Proteins p21(ras) genetics, Pyridones pharmacology, Pyrimidinones pharmacology, Triazoles pharmacology, Xenograft Model Antitumor Assays, Azepines administration & dosage, Colorectal Neoplasms drug therapy, Drug Resistance, Neoplasm drug effects, Gene Regulatory Networks drug effects, Interferons metabolism, Pyridones administration & dosage, Pyrimidinones administration & dosage, Triazoles administration & dosage
Abstract

Despite showing clinical activity in BRAF-mutant melanoma, the MEK inhibitor (MEKi) trametinib has failed to show clinical benefit in KRAS-mutant colorectal cancer. To identify mechanisms of resistance to MEKi, we employed a pharmacogenomic analysis of MEKi-sensitive versus MEKi-resistant colorectal cancer cell lines. Strikingly, interferon- and inflammatory-related gene sets were enriched in cell lines exhibiting intrinsic and acquired resistance to MEK inhibition. The bromodomain inhibitor JQ1 suppressed interferon-stimulated gene (ISG) expression and in combination with MEK inhibitors displayed synergistic effects and induced apoptosis in MEKi-resistant colorectal cancer cell lines. ISG expression was confirmed in patient-derived organoid models, which displayed resistance to trametinib and were resensitized by JQ1 co-treatment. In in vivo models of colorectal cancer, combination treatment significantly suppressed tumor growth. Our findings provide a novel explanation for the limited response to MEK inhibitors in KRAS-mutant colorectal cancer, known for its inflammatory nature. Moreover, the high expression of ISGs was associated with significantly reduced survival of colorectal cancer patients. Excitingly, we have identified novel therapeutic opportunities to overcome intrinsic and acquired resistance to MEK inhibition in colorectal cancer.

Published
2019
Full Text
View/download PDF

39. Longitudinal Liquid Biopsy and Mathematical Modeling of Clonal Evolution Forecast Time to Treatment Failure in the PROSPECT-C Phase II Colorectal Cancer Clinical Trial.

Author

Khan KH, Cunningham D, Werner B, Vlachogiannis G, Spiteri I, Heide T, Mateos JF, Vatsiou A, Lampis A, Damavandi MD, Lote H, Huntingford IS, Hedayat S, Chau I, Tunariu N, Mentrasti G, Trevisani F, Rao S, Anandappa G, Watkins D, Starling N, Thomas J, Peckitt C, Khan N, Rugge M, Begum R, Hezelova B, Bryant A, Jones T, Proszek P, Fassan M, Hahne JC, Hubank M, Braconi C, Sottoriva A, and Valeri N

Subjects
Adult, Aged, Aged, 80 and over, Clinical Trials as Topic, Clonal Evolution, Colorectal Neoplasms pathology, Female, Humans, Male, Middle Aged, Models, Theoretical, Time-to-Treatment, Treatment Failure, Colorectal Neoplasms diagnosis, Liquid Biopsy methods
Abstract

Sequential profiling of plasma cell-free DNA (cfDNA) holds immense promise for early detection of patient progression. However, how to exploit the predictive power of cfDNA as a liquid biopsy in the clinic remains unclear. RAS pathway aberrations can be tracked in cfDNA to monitor resistance to anti-EGFR monoclonal antibodies in patients with metastatic colorectal cancer. In this prospective phase II clinical trial of single-agent cetuximab in RAS wild-type patients, we combine genomic profiling of serial cfDNA and matched sequential tissue biopsies with imaging and mathematical modeling of cancer evolution. We show that a significant proportion of patients defined as RAS wild-type based on diagnostic tissue analysis harbor aberrations in the RAS pathway in pretreatment cfDNA and, in fact, do not benefit from EGFR inhibition. We demonstrate that primary and acquired resistance to cetuximab are often of polyclonal nature, and these dynamics can be observed in tissue and plasma. Furthermore, evolutionary modeling combined with frequent serial sampling of cfDNA allows prediction of the expected time to treatment failure in individual patients. This study demonstrates how integrating frequently sampled longitudinal liquid biopsies with a mathematical framework of tumor evolution allows individualized quantitative forecasting of progression, providing novel opportunities for adaptive personalized therapies. Significance: Liquid biopsies capture spatial and temporal heterogeneity underpinning resistance to anti-EGFR monoclonal antibodies in colorectal cancer. Dense serial sampling is needed to predict the time to treatment failure and generate a window of opportunity for intervention. Cancer Discov; 8(10); 1270-85. ©2018 AACR. See related commentary by Siravegna and Corcoran, p. 1213 This article is highlighted in the In This Issue feature, p. 1195 ., (©2018 American Association for Cancer Research.)

Published
2018
Full Text
View/download PDF

40. Functional imaging and circulating biomarkers of response to regorafenib in treatment-refractory metastatic colorectal cancer patients in a prospective phase II study.

Author

Khan K, Rata M, Cunningham D, Koh DM, Tunariu N, Hahne JC, Vlachogiannis G, Hedayat S, Marchetti S, Lampis A, Damavandi MD, Lote H, Rana I, Williams A, Eccles SA, Fontana E, Collins D, Eltahir Z, Rao S, Watkins D, Starling N, Thomas J, Kalaitzaki E, Fotiadis N, Begum R, Bali M, Rugge M, Temple E, Fassan M, Chau I, Braconi C, and Valeri N

Subjects
Adult, Aged, Biomarkers blood, Colorectal Neoplasms blood, Colorectal Neoplasms diagnostic imaging, Female, Humans, Kaplan-Meier Estimate, Magnetic Resonance Imaging, Male, Middle Aged, Prospective Studies, Treatment Outcome, Colorectal Neoplasms drug therapy, Phenylurea Compounds therapeutic use, Pyridines therapeutic use
Abstract

Objective: Regorafenib demonstrated efficacy in patients with metastatic colorectal cancer (mCRC). Lack of predictive biomarkers, potential toxicities and cost-effectiveness concerns highlight the unmet need for better patient selection., Design: Patients with RAS mutant mCRC with biopsiable metastases were enrolled in this phase II trial. Dynamic contrast-enhanced (DCE) MRI was acquired pretreatment and at day 15 post-treatment. Median values of volume transfer constant (K trans ), enhancing fraction (EF) and their product KEF (summarised median values of K trans × EF) were generated. Circulating tumour (ct) DNA was collected monthly until progressive disease and tested for clonal RAS mutations by digital-droplet PCR. Tumour vasculature (CD-31) was scored by immunohistochemistry on 70 sequential tissue biopsies., Results: Twenty-seven patients with paired DCE-MRI scans were analysed. Median KEF decrease was 58.2%. Of the 23 patients with outcome data, >70% drop in KEF (6/23) was associated with higher disease control rate (p=0.048) measured by RECIST V. 1.1 at 2 months, improved progression-free survival (PFS) (HR 0.16 (95% CI 0.04 to 0.72), p=0.02), 4-month PFS (66.7% vs 23.5%) and overall survival (OS) (HR 0.08 (95% CI 0.01 to 0.63), p=0.02). KEF drop correlated with CD-31 reduction in sequential tissue biopsies (p=0.04). RAS mutant clones decay in ctDNA after 8 weeks of treatment was associated with better PFS (HR 0.21 (95% CI 0.06 to 0.71), p=0.01) and OS (HR 0.28 (95% CI 0.07-1.04), p=0.06)., Conclusions: Combining DCE-MRI and ctDNA predicts duration of anti-angiogenic response to regorafenib and may improve patient management with potential health/economic implications., Competing Interests: Competing interests: DC received research funding from: Roche, Amgen, Celgene,Sanofi, Merck Serono, Novartis, AstraZeneca, Bayer, Merrimack and MedImmune. KK has had advisory role with Bayer. IC has had advisory roles with Merck Serono, Roche, Sanofi Oncology, Bristol Myers Squibb, Eli-Lilly, Novartis, Gilead Science. He has received research funding from Merck-Serono, Novartis, Roche and Sanofi Oncology, and honoraria from Roche, Sanofi-Oncology, Eli-Lilly, Taiho. All other authors declare no conflict of interest, (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Published
2018
Full Text
View/download PDF

41. Patient-derived organoids model treatment response of metastatic gastrointestinal cancers.

Author

Vlachogiannis G, Hedayat S, Vatsiou A, Jamin Y, Fernández-Mateos J, Khan K, Lampis A, Eason K, Huntingford I, Burke R, Rata M, Koh DM, Tunariu N, Collins D, Hulkki-Wilson S, Ragulan C, Spiteri I, Moorcraft SY, Chau I, Rao S, Watkins D, Fotiadis N, Bali M, Darvish-Damavandi M, Lote H, Eltahir Z, Smyth EC, Begum R, Clarke PA, Hahne JC, Dowsett M, de Bono J, Workman P, Sadanandam A, Fassan M, Sansom OJ, Eccles S, Starling N, Braconi C, Sottoriva A, Robinson SP, Cunningham D, and Valeri N

Subjects
Animals, Antineoplastic Agents therapeutic use, Gastrointestinal Neoplasms pathology, Genomics, Humans, Mice, Neoplasm Metastasis, Organoids metabolism, Phenylurea Compounds pharmacology, Phenylurea Compounds therapeutic use, Pyridines pharmacology, Pyridines therapeutic use, Antineoplastic Agents pharmacology, Drug Resistance, Neoplasm, Gastrointestinal Neoplasms drug therapy, Organoids drug effects, Precision Medicine methods, Xenograft Model Antitumor Assays
Abstract

Patient-derived organoids (PDOs) have recently emerged as robust preclinical models; however, their potential to predict clinical outcomes in patients has remained unclear. We report on a living biobank of PDOs from metastatic, heavily pretreated colorectal and gastroesophageal cancer patients recruited in phase 1/2 clinical trials. Phenotypic and genotypic profiling of PDOs showed a high degree of similarity to the original patient tumors. Molecular profiling of tumor organoids was matched to drug-screening results, suggesting that PDOs could complement existing approaches in defining cancer vulnerabilities and improving treatment responses. We compared responses to anticancer agents ex vivo in organoids and PDO-based orthotopic mouse tumor xenograft models with the responses of the patients in clinical trials. Our data suggest that PDOs can recapitulate patient responses in the clinic and could be implemented in personalized medicine programs., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Published
2018
Full Text
View/download PDF

42. KRAS and BRAF mutations in circulating tumour DNA from locally advanced rectal cancer.

Author

Sclafani F, Chau I, Cunningham D, Hahne JC, Vlachogiannis G, Eltahir Z, Lampis A, Braconi C, Kalaitzaki E, De Castro DG, Wotherspoon A, Capdevila J, Glimelius B, Tarazona N, Begum R, Lote H, Hulkki Wilson S, Mentrasti G, Brown G, Tait D, Oates J, and Valeri N

Subjects
Aged, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Capecitabine administration & dosage, Capecitabine therapeutic use, Cetuximab administration & dosage, Cetuximab therapeutic use, Chemoradiotherapy, Adjuvant, Digestive System Surgical Procedures, Female, Humans, Male, Middle Aged, Organoplatinum Compounds administration & dosage, Organoplatinum Compounds therapeutic use, Oxaliplatin, Prognosis, Rectal Neoplasms genetics, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Circulating Tumor DNA genetics, Mutation, Proto-Oncogene Proteins B-raf genetics, Proto-Oncogene Proteins p21(ras) genetics, Rectal Neoplasms therapy
Abstract

There are limited data on circulating, cell-free, tumour (ct)DNA analysis in locally advanced rectal cancer (LARC). Digital droplet (dd)PCR was used to investigate KRAS/BRAF mutations in ctDNA from baseline blood samples of 97 LARC patients who were treated with CAPOX followed by chemoradiotherapy, surgery and adjuvant CAPOX ± cetuximab in a randomised phase II trial. KRAS mutation in G12D, G12V or G13D was detected in the ctDNA of 43% and 35% of patients with tumours that were mutant and wild-type for these hotspot mutations, respectively, according to standard PCR-based analyses on tissue. The detection rate in the ctDNA of 10 patients with less common mutations was 50%. In 26 cases ctDNA analysis revealed KRAS mutations that were not previously found in tissue. Twenty-two of these (84.6%) were detected following repeat tissue testing by ddPCR. Overall, the ctDNA detection rate in the KRAS mutant population was 66%. Detection of KRAS mutation in ctDNA failed to predict prognosis or refine patient selection for cetuximab. While this study confirms the feasibility of ctDNA analysis in LARC and the high sensitivity of ddPCR, larger series are needed to better address the role of ctDNA as a prognostic or predictive tool in this setting.

Published
2018
Full Text
View/download PDF

44. Bloodstream infections and sepsis in Greece: over-time change of epidemiology and impact of de-escalation on final outcome.

Author

Koupetori M, Retsas T, Antonakos N, Vlachogiannis G, Perdios I, Nathanail C, Makaritsis K, Papadopoulos A, Sinapidis D, Giamarellos-Bourboulis EJ, Pneumatikos I, Gogos C, Armaganidis A, and Paramythiotou E

Subjects
Aged, Female, Greece epidemiology, Humans, Incidence, Intensive Care Units, Long-Term Care, Male, Middle Aged, Prospective Studies, Sepsis epidemiology, Anti-Bacterial Agents, Bacteremia epidemiology, Bacteremia microbiology, Drug Resistance, Multiple, Bacterial
Abstract

Background: Choice of empirically prescribed antimicrobials for sepsis management depends on epidemiological factors. The epidemiology of sepsis in Greece was studied in two large-periods., Methods: Sepsis due to bloodstream infections (BSI) from July 2006 until March 2013 was recorded in a multicenter study in 46 departments. Patients were divided into sepsis admitted in the emergencies and hospitalized in the general ward (GW) and sepsis developing after admission in the Intensive Care Unit (ICU). The primary endpoints were the changes of epidemiology and the factors related with BSIs by multidrug-resistant (MDR) pathogens; the secondary endpoint was the impact of de-escalation on antimicrobial therapy., Results: 754 patients were studied; 378 from 2006-2009 and 376 from 2010-2013. Major differences were recorded between periods in the GW. They involved increase of: sepsis severity; the incidence of underlying diseases; the incidence of polymicrobial infections; the emergence of Klebsiella pneumoniae as a pathogen; and mortality. Factors independently related with BSI by MDR pathogens were chronic hemofiltration, intake of antibiotics the last three months and residence into long-term care facilities. De-escalation in BSIs by fully susceptible Gram-negatives did not affect final outcome. Similar epidemiological differences were not found in the ICU; MDR Gram-negatives predominated in both periods., Conclusions: The epidemiology of sepsis in Greece differs in the GW and in the ICU. De-escalation in the GW is a safe strategy.

Published
2014
Full Text
View/download PDF

45. The first hypervariable region of the gp120 Env glycoprotein defines the neutralizing susceptibility of heterologous human immunodeficiency virus type 1 isolates to neutralizing antibodies elicited by the SF162gp140 immunogen.

Author

Ching LK, Vlachogiannis G, Bosch KA, and Stamatatos L

Subjects
Cell Line, HIV Envelope Protein gp120 genetics, HIV-1 genetics, Humans, Neutralization Tests, Peptide Fragments genetics, AIDS Vaccines immunology, Cross Reactions, HIV Antibodies immunology, HIV Envelope Protein gp120 immunology, HIV-1 immunology, Peptide Fragments immunology, env Gene Products, Human Immunodeficiency Virus immunology
Abstract

Current vaccine efforts to elicit cross-reactive neutralizing antibodies (NAbs) against human immunodeficiency virus (HIV) focus on the engineering of soluble mimetics of the trimeric HIV Env glycoprotein (commonly termed gp140 immunogens). Such immunogens are thought to be more effective than previously tested monomeric gp120 immunogens at eliciting cross-reactive NAbs. Still, the breadth of neutralizing antibody responses elicited by gp140 immunogens is narrow. Understanding why antibodies elicited by gp140 immunogens fail to neutralize a wide range of heterologous primary HIV isolates is necessary for improving the design of such immunogens. We previously reported that antibodies elicited in macaques by SF162 Env-derived gp140 immunogens fail to neutralize several heterologous "neutralization-resistant" primary HIV type 1 isolates, such as JRFL, ADA, and YU2. Here we show that by replacing the V1 region of Env on these heterologous viruses with that of SF162, we render them highly susceptible to neutralization by the SF162gp140-elicited antibodies. We observed that viral neutralization was mediated not only by vaccine-elicited anti-V1 but also by anti-V3 antibodies and antibodies directed against as yet unidentified Env regions, depending on the heterologous Env background. Our study indicates that common neutralization epitopes are differentially exposed on diverse primary HIV isolates and that the V1 loop contributes to this differential exposure. Therefore, the antibody responses elicited by soluble gp140 immunogens will have to overcome several distinct obstacles in order to neutralize diverse primary HIV isolates.

Published
2008
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results