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345 results on '"Papandreou C"'

1. Final results from the PERUSE study of first-line pertuzumab plus trastuzumab plus a taxane for HER2-positive locally recurrent or metastatic breast cancer, with a multivariable approach to guide prognostication

Author

Bachelot, T., Bouzid, K., Campone, M., Desmoulins, I., Coudert, B., Bondarenko, I., Nowecki, Z., Glogowska, I., Ciruelos Gil, E., Errihani, H., Dalenc, F., Ricci, F., Dieras, V., Kaufman, B., Paluch-Shimon, S., Wardley, A., Schneeweiss, A., Ferreira, A., Mano, M., Kalofonos, H., Andreetta, C., Puglisi, F., Montemurro, F., Barrett, S., Zhang, Q., Mavroudis, D., Matus, J., Villarreal Garza, C., Beato, C., Ismael, G., Hu, X., Abdel Azeem, H., Gaafar, R., Perrin, C., Kerbrat, P., Ettl, J., Paepke, S., Hitre, E., Lang, I., Trudeau, M., Verma, S., Li, H., Hoffmann, O., Aktas, B., Cariello, A., Cruciani, G., Tienghi, A., Tondini, C., Al-Twegieri, T., Loman, N., Laing, R., Miles, D., Brain, E., Fasching, P., Lux, M., Frassoldati, A., Aziz, Z., Salas, J., Streb, J., Krzemieniecki, K., Wronski, A., Garcia Garcia, J., Menjon Beltran, S., Cicin, I., Schmid, P., Gallagher, C., Turner, N., Tong, Z., Boer, K., Juhász, B., Horvath, Z., Bianchini, G., Gianni, L., Curigliano, G., Juarez Ramiro, A., Susnjar, S., Matos, E., Sevillano, E., Garcia Estevez, L., Gokmen, E., Uslu, R., Wildiers, H., Schutz, F., Cruz, M., Bourgeois, H., von Schumann, R., Stemmer, S., Dominguez, A., Morales-Vásques, F., Wojtukiewicz, M., Trifunovic, J., Echarri Gonzalez, M.J., Illarramendi Mañas, J., Martinez De Dueñas, E., Voitko, N., Hicks, J., Waters, S., Barrett-Lee, P., Wheatley, D., De Boer, R., Cocquyt, V., Jerusalem, G., Barrios, C., Panasci, L., Mattson, J., Tanner, M., Gozy, M., Vasilopoulos, G., Papandreou, C., Revesz, J., Battelli, N., Benedetti, G., Latini, L., Gridelli, C., Lazaro Leon, J., Alarcón Company, J., Arance Fernandez, A., Barnadas Molins, A., Calvo Plaza, I., Bratos, R., Gonzalez Martin, A., Izarzugaza Peron, Y., Klint, L., Kovalev, A., McCarthy, N., Yeo, B., Kee, D., Thomson, J., White, S., Greil, R., Wang, S., Artignan, X., Juhasz-Böess, I., Rody, A., Ngan, R., Dourleshter, F., Goldberg, H., Doni, L., Di Costanzo, F., Ferraù, F., Drobniene, M., Aleknavicius, E., Rashid, K., Costa, L., de la Cruz Merino, L., Garcia Saenz, J., López, R., Del Val Munoz, O., Ozyilkan, O., Azribi, F., Jaafar, H., Baird, R., Verrill, M., Beith, J., Petzer, A., Moreira de Andrade, J., Bernstein, V., Macpherson, N., Rayson, D., Saad Eldin, I., Achille, M., Augereau, P., Müller, V., Rasco, A., Evron, E., Katz, D., Berardi, R., Cascinu, S., De Censi, A., Gennari, A., El-Saghir, N., Ghosn, M., Oosterkamp, H.M., Van den Bosch, J., Kukulska, M., Kalinka, E., Alonso, J., Dalmau Portulas, E., Del Mar Gordon Santiago, M., Pelaez Fernandez, I., Aksoy, S., Altundag, K., Senol Coskun, H., Bozcuk, H., Shparyk, Y., Barraclough, L., Levitt, N., Panwar, U., Kelly, S., Rigg, A., Varughese, M., Castillo, C., Fein, L., Malik, L., Stuart-Harris, R., Singer, C., Stoeger, H., Samonigg, H., Feng, J., Cedeño, M., Ruohola, J., Berdah, J.-F., Goncalves, A., Orfeuvre, H., Grischke, E.-M., Simon, E., Wagner, S., Koumakis, G., Papazisis, K., Ben Baruch, N., Fried, G., Geffen, D., Karminsky, N., Peretz, T., Cavanna, L., Pedrazzioli, P., Grasso, D., Ruggeri, E., D’Auria, G., Moscetti, L., Juozaityte, E., Rodriguez Cid, J., Roerdink, H., Siddiqi, N., Passos Coelho, J., Arcediano Del Amo, A., Garcia Garre, E., García Gonzalez, M., Garcia-Palomo Perez, A., Herenandez Perez, C., Lopez Alvarez, P., Lopez De Ceballos, M.H., Martínez Jañez, N., Mele Olive, M., McAdam, K., Perren, T., Dunn, G., Humphreys, A., Taylor, W., Vera, R., Kaen, L., Andel, J., Steger, G., De Grève, J., Huizing, M., Hegg, R., Joy, A., Kuruvilla, P., Sehdev, S., Smiljanic, S., Kütner, R., Alexandre, J., Grosjean, J., Laplaige, P., Largillier, R., Maes, P., Martin, P., Pottier, V., Christensen, B., Khandan, F., Lück, H.-J., Zahm, D.-M., Fountzilas, G., Karavasilis, V., Safra, T., Inbar, M., Ryvo, L., Bonetti, A., Seles, E., Giacobino, A., Chavarri Guerra, Y., de Jongh, F., van der Velden, A., van Warmerdam, L., Vrijaldenhoven, S., Smorenburg, C.H., Cavero, M., Andres Conejero, R., Oltra Ferrando, A., Redondo Sanchez, A., Ribelles Entrena, N., Saura Grau, S., Viñas Vilaro, G., Bachmeier, K., Beresford, M., Butt, M., Joffe, J., Poole, C., Woodings, P., Chakraborti, P., Yordi, G., Woodward, N., Nobre, A., Luiz Amorim, G., Califaretti, N., Fox, S., Robidoux, A., Li, E., Li, N., Jiang, J., Soria, T., Padrik, P., Lahdenpera, O., Barletta, H., Dohollou, N., Genet, D., Prulhiere, K., Coeffic, D., Facchini, T., Vieillot, S., Catala, S., Teixeira, L., Hesse, T., Kühn, T., Ober, A., Repp, R., Schröder, W., Pectasides, D., Bodoky, G., Kahan, Z., Jiveliouk, I., Rosengarten, O., Rossi, V., Alabiso, O., Pérez Martínez, M., van de Wouw, A.J., Smok-Kalwat, J., Damasecno, M., Augusto, I., Sousa, G., Saadein, A., Abdelhafiez, N., Abulkhair, O., Antón Torres, A., Corbellas Aparicio, M., Llorente Domenech, R., Florián Jerico, J., Garcia Mata, J., Gil Raga, M., Galan Brotons, A., Llombart Cussac, A., Llorca Ferrandiz, C., Martinez Del Prado, P., Olier Garate, C., Rodriguez Sanchez, C., Sanchez Gomez, R., Santisteban Eslava, M., Soberino, J., Vidal Losada Garcia, M., Soto de Prado, D., Torrego Garcia, J., Vicente Rubio, E., Garcia, M., Murias Rosales, A., Granstam Björneklett, H., Narbe, U., Jafri, M., Rea, D., Newby, J., Jones, A., Westwell, S., Ring, A., Alonso, I., Rodríguez, R., Ciruelos, E., Peretz-Yablonski, T., Merot, J.-L., Trask, P., du Toit, Y., Pena-Murillo, C., Revelant, V., and Klingbiel, D.

Published
2021
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2. Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer

Author

Zhang, Q., Xu, B., Shao, Z., Wang, X., Geng, C., Yan, X., Tong, Z., Shen, K., Yin, Y., Sun, T., Yang, J., Feng, J., Yan, M., Wang, Y., Liu, Q., Zhang, S., De Laurentiis, M., Santoro, A., Guarneri, V., Colleoni, M., Natoli, C., Cortesi, L., Placido, S., Gianni, L., Ferrau, F., Livi, L., Zambelli, A., Del Mastro, L., Tonini, G., Montemurro, F., Bianchi, G., Pedersini, R., Prete, S., Allegrini, G., Naso, G., Vici, P., Loirat, D., Mailliez, A., Priou, F., Tredan, O., Dalenc, F., Perrin, C., Gligorov, J., Timar David, M., Dohollou, N., Teixeira, L., Brocard, F., Arnaud, A., Delaloge, S., Spano, J.-P., Mansi, L., Andrade, L., Damian, F., Pedrini, J., Aleixo, S., Hegg, R., Junior, R., Reinisch, M., Schmidt, M., Wenzel, C., Grischke, E.-M., Schneeweiss, A., Just, M., Harbeck, N., Schumacher, C., Peters, U., Fischer, D., Forstbauer, H., Liersch, R., Warner, E., Bouganim, N., Doyle, C., Price Hiller, J., Vandenberg, T., Pavic, M., Robinson, A., Roldan Urgoiti, G., Califaretti, N., Alacacioglu, A., Gumus, M., Yalcin, B., Cicin, I., Kose, F., Uygun, K., Kaplan, M., Cubukcu, E., Wardley, A., Harries, M., Miles, D., Doval, D., Gupta, S., Mohapatra, P., Chatterjee, S., Ghadyalpatil, N., Singhal, M., Nag, S., Agarwal, A., Wolf, I., Gal Yam, E., Yerushalmi, R., Peretz, T., Fried, G., Ben Baruch, N., Katz, D., Hamilton, E., Kayali, F., Brufsky, A., Telli, M., Wright, G., Oyola, R., Rakowski, T., Graff, S., Tjulandin, S., Semiglazov, V., Aparicio, A., Ruiz Borrego, M., Merino, L., Guerra Martinez, J., Lopez, E., Yamashita, T., Ohtani, S., Inoue, K., Ito, Y., Niikura, N., Nakayama, T., Sagara, Y., Yanagita, Y., Kamada, Y., Kaneko, K., Kaen, D., Nervo, A., Eniu, A., Schenker, M., Priester, P., Melichar, B., Zimovjanova, M., Sormova, P., Sufliarsky, J., Kakalejcik, M., Belbaraka, R., Errihani, H., Le Than, D., Pham, D., Aravantinos, G., Papadimitriou, C., Koumakis, G., Papandreou, C., Podolski, P., Tabane, K., André, F., Cameron, D., Barrios, C., Patel, S., Patre, M., Morales, L., Patel, S.L., Kaul, M., Barata, T., and O’Shaughnessy, J.

Published
2021
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3. Exploring small non-coding RNAs as blood-based biomarkers to predict Alzheimer's disease

Author

Universitat Rovira i Virgili, Gutierrez-Tordera, L; Papandreou, C; Novau-Ferre, N; Garcia-Gonzalez, P; Rojas, M; Marquie, M; Chapado, LA; Papagiannopoulos, C; Fernandez-Castillo, N; Valero, S; Folch, J; Ettcheto, M; Camins, A; Boada, M; Ruiz, A; Bullo, M, Universitat Rovira i Virgili, and Gutierrez-Tordera, L; Papandreou, C; Novau-Ferre, N; Garcia-Gonzalez, P; Rojas, M; Marquie, M; Chapado, LA; Papagiannopoulos, C; Fernandez-Castillo, N; Valero, S; Folch, J; Ettcheto, M; Camins, A; Boada, M; Ruiz, A; Bullo, M

Abstract

Alzheimer's disease (AD) diagnosis relies on clinical symptoms complemented with biological biomarkers, the Amyloid Tau Neurodegeneration (ATN) framework. Small non-coding RNA (sncRNA) in the blood have emerged as potential predictors of AD. We identified sncRNA signatures specific to ATN and AD, and evaluated both their contribution to improving AD conversion prediction beyond ATN alone.This nested case-control study was conducted within the ACE cohort and included MCI patients matched by sex. Patients free of type 2 diabetes underwent cerebrospinal fluid (CSF) and plasma collection and were followed-up for a median of 2.45-years. Plasma sncRNAs were profiled using small RNA-sequencing. Conditional logistic and Cox regression analyses with elastic net penalties were performed to identify sncRNA signatures for A+(T|N)+ and AD. Weighted scores were computed using cross-validation, and the association of these scores with AD risk was assessed using multivariable Cox regression models. Gene ontology (GO) and Kyoto encyclopaedia of genes and genomes (KEGG) enrichment analysis of the identified signatures were performed.The study sample consisted of 192 patients, including 96 A+(T|N)+ and 96 A-T-N- patients. We constructed a classification model based on a 6-miRNAs signature for ATN. The model could classify MCI patients into A-T-N- and A+(T|N)+ groups with an area under the curve of 0.7335 (95% CI, 0.7327 to 0.7342). However, the addition of the model to conventional risk factors did not improve the prediction of AD beyond the conventional model plus ATN status (C-statistic: 0.805 [95% CI, 0.758 to 0.852] compared to 0.829 [95% CI, 0.786, 0.872]). The AD-related 15-sncRNAs signature exhibited better predictive performance than the conventional model plus ATN status (C-stati

Published
2024

5. Lipoprotein Particle Profiles Associated with Telomere Length and Telomerase Complex Components

Author

Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Novau-Ferré, N; Rojas, M; Gutierrez-Tordera, L; Arcelin, P; Folch, J; Papandreou, C; Bulló, M, Bioquímica i Biotecnologia, Universitat Rovira i Virgili, and Novau-Ferré, N; Rojas, M; Gutierrez-Tordera, L; Arcelin, P; Folch, J; Papandreou, C; Bulló, M

Abstract

Telomere length (TL) is a well-known marker of age-related diseases. Oxidative stress and inflammation increase the rate of telomere shortening, triggering cellular senescence. Although lipoproteins could have anti-inflammatory and proinflammatory functional properties, the relationship between lipoprotein particles with TL and telomerase activity-related genes has not been investigated much. In this study, we assessed the associations of lipoprotein subfractions with telomere length, TERT, and WRAP53 expression in a total of 54 pre-diabetic subjects from the EPIRDEM study. We regressed TL, TERT, and WRAP53 on 12 lipoprotein subclasses, employing a Gaussian linear regression method with Lasso penalty to determine a lipoprotein profile associated with telomere-related parameters. The covariates included age, sex, body mass index (BMI), dyslipidemia, statin consumption, and physical activity leisure time. We identified a lipoprotein profile composed of four lipoprotein subfractions associated with TL (Pearson r = 0.347, p-value = 0.010), two lipoprotein subfractions associated with TERT expression (Pearson r = 0.316, p-value = 0.020), and five lipoprotein subfractions associated with WRAP53 expression (Pearson r = 0.379, p-value =0.005). After adjusting for known confounding factors, most lipoprotein profiles maintained the association with TL, TERT, and WRAP53. Overall, medium and small-sized HDL particles were associated with shorter telomeres and lower expression of TERT and WRAP53. Large HDL particles were associated with longer telomere and lower expression of WRAP53, but not with TERT. Our results suggest that the lipoprotein profiles are associated with telomere length, TERT, and WRAP53 expression and should be considered when assessing the risk of chronic diseases

Published
2023

6. EP10.01-018 Thromboprophylaxis for Lung Cancer Patients: Results From ACT4CAT Trial

Author

Tsoukalas, N., primary, Christopoulou, A., additional, Timotheadou, E., additional, Athanasiadis, I., additional, Koumarianou, A., additional, Peroukidis, S., additional, Samelis, G., additional, Psyrri, A., additional, Kapodistrias, N., additional, Nikolakopoulos, A., additional, Andreadis, C., additional, Ardavanis, A., additional, Kalofonos, C., additional, Samantas, E., additional, Papandreou, C., additional, Mavroudis, D., additional, Bokas, A., additional, Barbounis, V., additional, Kentepozidis, N., additional, Athanasiadis, A., additional, Papakotoulas, P., additional, and Boukovinas, I., additional

Published
2022
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8. Enabling Value-Generating Telecommunications Services upon Integrated Multiservice Networks

Author

Adamopoulos, D. X., Papandreou, C. A., Hutchison, David, editor, Kanade, Takeo, editor, Kittler, Josef, editor, Kleinberg, Jon M., editor, Mattern, Friedemann, editor, Mitchell, John C., editor, Naor, Moni, editor, Nierstrasz, Oscar, editor, Pandu Rangan, C., editor, Steffen, Bernhard, editor, Sudan, Madhu, editor, Terzopoulos, Demetri, editor, Tygar, Dough, editor, Vardi, Moshe Y., editor, Weikum, Gerhard, editor, de Souza, José Neuman, editor, Dini, Petre, editor, and Lorenz, Pascal, editor

Published
2004
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9. PO-45: Cancer-associated thrombosis (CAT) in gynecological cancers: data from ACT4CAT study

Author

Tsoukalas, N., primary, Christopoulou, A., additional, Timotheadou, E., additional, Athanasiadis, I., additional, Koumarianou, A., additional, Peroukidis, S., additional, Samelis, G., additional, Psyrri, A., additional, Kapodistrias, N., additional, Nikolakopoulos, A., additional, Andreadis, C., additional, Ardavanis, A., additional, Samantas, E., additional, Papandreou, C., additional, Mavroudis, D., additional, Bokas, A., additional, Barbounis, V., additional, Kentepozidis, N., additional, Athanasiadis, A., additional, Papakotoulas, P., additional, and Boukovinas, I., additional

Published
2022
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11. Should patients with active urological cancers receive thromboprophylaxis for Cancer Associated Thrombosis (CAT)?

Author

Tsoukalas, N.G., primary, Christopoulou, A., additional, Timotheadou, E., additional, Koumarianou, A., additional, Athanasiadis, I., additional, Peroukidis, S., additional, Samelis, G., additional, Psyrri, A., additional, Papandreou, C., additional, Kapodistrias, N., additional, Papatsimpas, G., additional, Papakostas, P., additional, Aravantinos, G., additional, Ziras, N., additional, Nikolakopoulos, A., additional, Demiri, S., additional, Andreadis, C., additional, Ardavanis, A., additional, Sgouros, I., additional, Bokas, A., additional, Barbounis, V., additional, Kentepozidis, N., additional, Mavroudis, D., additional, Papakotoulas, P., additional, and Boukovinas, I., additional

Published
2021
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12. Final results from the PERUSE study of first-line pertuzumab plus trastuzumab plus a taxane for HER2-positive locally recurrent or metastatic breast cancer, with a multivariable approach to guide prognostication

Author

Miles, D., primary, Ciruelos, E., additional, Schneeweiss, A., additional, Puglisi, F., additional, Peretz-Yablonski, T., additional, Campone, M., additional, Bondarenko, I., additional, Nowecki, Z., additional, Errihani, H., additional, Paluch-Shimon, S., additional, Wardley, A., additional, Merot, J.-L., additional, Trask, P., additional, du Toit, Y., additional, Pena-Murillo, C., additional, Revelant, V., additional, Klingbiel, D., additional, Bachelot, T., additional, Bouzid, K., additional, Desmoulins, I., additional, Coudert, B., additional, Glogowska, I., additional, Ciruelos Gil, E., additional, Dalenc, F., additional, Ricci, F., additional, Dieras, V., additional, Kaufman, B., additional, Ferreira, A., additional, Mano, M., additional, Kalofonos, H., additional, Andreetta, C., additional, Montemurro, F., additional, Barrett, S., additional, Zhang, Q., additional, Mavroudis, D., additional, Matus, J., additional, Villarreal Garza, C., additional, Beato, C., additional, Ismael, G., additional, Hu, X., additional, Abdel Azeem, H., additional, Gaafar, R., additional, Perrin, C., additional, Kerbrat, P., additional, Ettl, J., additional, Paepke, S., additional, Hitre, E., additional, Lang, I., additional, Trudeau, M., additional, Verma, S., additional, Li, H., additional, Hoffmann, O., additional, Aktas, B., additional, Cariello, A., additional, Cruciani, G., additional, Tienghi, A., additional, Tondini, C., additional, Al-Twegieri, T., additional, Loman, N., additional, Laing, R., additional, Miles, D., additional, Brain, E., additional, Fasching, P., additional, Lux, M., additional, Frassoldati, A., additional, Aziz, Z., additional, Salas, J., additional, Streb, J., additional, Krzemieniecki, K., additional, Wronski, A., additional, Garcia Garcia, J., additional, Menjon Beltran, S., additional, Cicin, I., additional, Schmid, P., additional, Gallagher, C., additional, Turner, N., additional, Tong, Z., additional, Boer, K., additional, Juhász, B., additional, Horvath, Z., additional, Bianchini, G., additional, Gianni, L., additional, Curigliano, G., additional, Juarez Ramiro, A., additional, Susnjar, S., additional, Matos, E., additional, Sevillano, E., additional, Garcia Estevez, L., additional, Gokmen, E., additional, Uslu, R., additional, Wildiers, H., additional, Schutz, F., additional, Cruz, M., additional, Bourgeois, H., additional, von Schumann, R., additional, Stemmer, S., additional, Dominguez, A., additional, Morales-Vásques, F., additional, Wojtukiewicz, M., additional, Trifunovic, J., additional, Echarri Gonzalez, M.J., additional, Illarramendi Mañas, J., additional, Martinez De Dueñas, E., additional, Voitko, N., additional, Hicks, J., additional, Waters, S., additional, Barrett-Lee, P., additional, Wheatley, D., additional, De Boer, R., additional, Cocquyt, V., additional, Jerusalem, G., additional, Barrios, C., additional, Panasci, L., additional, Mattson, J., additional, Tanner, M., additional, Gozy, M., additional, Vasilopoulos, G., additional, Papandreou, C., additional, Revesz, J., additional, Battelli, N., additional, Benedetti, G., additional, Latini, L., additional, Gridelli, C., additional, Lazaro Leon, J., additional, Alarcón Company, J., additional, Arance Fernandez, A., additional, Barnadas Molins, A., additional, Calvo Plaza, I., additional, Bratos, R., additional, Gonzalez Martin, A., additional, Izarzugaza Peron, Y., additional, Klint, L., additional, Kovalev, A., additional, McCarthy, N., additional, Yeo, B., additional, Kee, D., additional, Thomson, J., additional, White, S., additional, Greil, R., additional, Wang, S., additional, Artignan, X., additional, Juhasz-Böess, I., additional, Rody, A., additional, Ngan, R., additional, Dourleshter, F., additional, Goldberg, H., additional, Doni, L., additional, Di Costanzo, F., additional, Ferraù, F., additional, Drobniene, M., additional, Aleknavicius, E., additional, Rashid, K., additional, Costa, L., additional, de la Cruz Merino, L., additional, Garcia Saenz, J., additional, López, R., additional, Del Val Munoz, O., additional, Ozyilkan, O., additional, Azribi, F., additional, Jaafar, H., additional, Baird, R., additional, Verrill, M., additional, Beith, J., additional, Petzer, A., additional, Moreira de Andrade, J., additional, Bernstein, V., additional, Macpherson, N., additional, Rayson, D., additional, Saad Eldin, I., additional, Achille, M., additional, Augereau, P., additional, Müller, V., additional, Rasco, A., additional, Evron, E., additional, Katz, D., additional, Berardi, R., additional, Cascinu, S., additional, De Censi, A., additional, Gennari, A., additional, El-Saghir, N., additional, Ghosn, M., additional, Oosterkamp, H.M., additional, Van den Bosch, J., additional, Kukulska, M., additional, Kalinka, E., additional, Alonso, J., additional, Dalmau Portulas, E., additional, Del Mar Gordon Santiago, M., additional, Pelaez Fernandez, I., additional, Aksoy, S., additional, Altundag, K., additional, Senol Coskun, H., additional, Bozcuk, H., additional, Shparyk, Y., additional, Barraclough, L., additional, Levitt, N., additional, Panwar, U., additional, Kelly, S., additional, Rigg, A., additional, Varughese, M., additional, Castillo, C., additional, Fein, L., additional, Malik, L., additional, Stuart-Harris, R., additional, Singer, C., additional, Stoeger, H., additional, Samonigg, H., additional, Feng, J., additional, Cedeño, M., additional, Ruohola, J., additional, Berdah, J.-F., additional, Goncalves, A., additional, Orfeuvre, H., additional, Grischke, E.-M., additional, Simon, E., additional, Wagner, S., additional, Koumakis, G., additional, Papazisis, K., additional, Ben Baruch, N., additional, Fried, G., additional, Geffen, D., additional, Karminsky, N., additional, Peretz, T., additional, Cavanna, L., additional, Pedrazzioli, P., additional, Grasso, D., additional, Ruggeri, E., additional, D’Auria, G., additional, Moscetti, L., additional, Juozaityte, E., additional, Rodriguez Cid, J., additional, Roerdink, H., additional, Siddiqi, N., additional, Passos Coelho, J., additional, Arcediano Del Amo, A., additional, Garcia Garre, E., additional, García Gonzalez, M., additional, Garcia-Palomo Perez, A., additional, Herenandez Perez, C., additional, Lopez Alvarez, P., additional, Lopez De Ceballos, M.H., additional, Martínez Jañez, N., additional, Mele Olive, M., additional, McAdam, K., additional, Perren, T., additional, Dunn, G., additional, Humphreys, A., additional, Taylor, W., additional, Vera, R., additional, Kaen, L., additional, Andel, J., additional, Steger, G., additional, De Grève, J., additional, Huizing, M., additional, Hegg, R., additional, Joy, A., additional, Kuruvilla, P., additional, Sehdev, S., additional, Smiljanic, S., additional, Kütner, R., additional, Alexandre, J., additional, Grosjean, J., additional, Laplaige, P., additional, Largillier, R., additional, Maes, P., additional, Martin, P., additional, Pottier, V., additional, Christensen, B., additional, Khandan, F., additional, Lück, H.-J., additional, Zahm, D.-M., additional, Fountzilas, G., additional, Karavasilis, V., additional, Safra, T., additional, Inbar, M., additional, Ryvo, L., additional, Bonetti, A., additional, Seles, E., additional, Giacobino, A., additional, Chavarri Guerra, Y., additional, de Jongh, F., additional, van der Velden, A., additional, van Warmerdam, L., additional, Vrijaldenhoven, S., additional, Smorenburg, C.H., additional, Cavero, M., additional, Andres Conejero, R., additional, Oltra Ferrando, A., additional, Redondo Sanchez, A., additional, Ribelles Entrena, N., additional, Saura Grau, S., additional, Viñas Vilaro, G., additional, Bachmeier, K., additional, Beresford, M., additional, Butt, M., additional, Joffe, J., additional, Poole, C., additional, Woodings, P., additional, Chakraborti, P., additional, Yordi, G., additional, Woodward, N., additional, Nobre, A., additional, Luiz Amorim, G., additional, Califaretti, N., additional, Fox, S., additional, Robidoux, A., additional, Li, E., additional, Li, N., additional, Jiang, J., additional, Soria, T., additional, Padrik, P., additional, Lahdenpera, O., additional, Barletta, H., additional, Dohollou, N., additional, Genet, D., additional, Prulhiere, K., additional, Coeffic, D., additional, Facchini, T., additional, Vieillot, S., additional, Catala, S., additional, Teixeira, L., additional, Hesse, T., additional, Kühn, T., additional, Ober, A., additional, Repp, R., additional, Schröder, W., additional, Pectasides, D., additional, Bodoky, G., additional, Kahan, Z., additional, Jiveliouk, I., additional, Rosengarten, O., additional, Rossi, V., additional, Alabiso, O., additional, Pérez Martínez, M., additional, van de Wouw, A.J., additional, Smok-Kalwat, J., additional, Damasecno, M., additional, Augusto, I., additional, Sousa, G., additional, Saadein, A., additional, Abdelhafiez, N., additional, Abulkhair, O., additional, Antón Torres, A., additional, Corbellas Aparicio, M., additional, Llorente Domenech, R., additional, Florián Jerico, J., additional, Garcia Mata, J., additional, Gil Raga, M., additional, Galan Brotons, A., additional, Llombart Cussac, A., additional, Llorca Ferrandiz, C., additional, Martinez Del Prado, P., additional, Olier Garate, C., additional, Rodriguez Sanchez, C., additional, Sanchez Gomez, R., additional, Santisteban Eslava, M., additional, Soberino, J., additional, Vidal Losada Garcia, M., additional, Soto de Prado, D., additional, Torrego Garcia, J., additional, Vicente Rubio, E., additional, Garcia, M., additional, Murias Rosales, A., additional, Granstam Björneklett, H., additional, Narbe, U., additional, Jafri, M., additional, Rea, D., additional, Newby, J., additional, Jones, A., additional, Westwell, S., additional, Ring, A., additional, Alonso, I., additional, and Rodríguez, R., additional

Published
2021
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15. Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer

Author

Miles, D., primary, Gligorov, J., additional, André, F., additional, Cameron, D., additional, Schneeweiss, A., additional, Barrios, C., additional, Xu, B., additional, Wardley, A., additional, Kaen, D., additional, Andrade, L., additional, Semiglazov, V., additional, Reinisch, M., additional, Patel, S., additional, Patre, M., additional, Morales, L., additional, Patel, S.L., additional, Kaul, M., additional, Barata, T., additional, O’Shaughnessy, J., additional, Zhang, Q., additional, Shao, Z., additional, Wang, X., additional, Geng, C., additional, Yan, X., additional, Tong, Z., additional, Shen, K., additional, Yin, Y., additional, Sun, T., additional, Yang, J., additional, Feng, J., additional, Yan, M., additional, Wang, Y., additional, Liu, Q., additional, Zhang, S., additional, De Laurentiis, M., additional, Santoro, A., additional, Guarneri, V., additional, Colleoni, M., additional, Natoli, C., additional, Cortesi, L., additional, Placido, S., additional, Gianni, L., additional, Ferrau, F., additional, Livi, L., additional, Zambelli, A., additional, Del Mastro, L., additional, Tonini, G., additional, Montemurro, F., additional, Bianchi, G., additional, Pedersini, R., additional, Prete, S., additional, Allegrini, G., additional, Naso, G., additional, Vici, P., additional, Loirat, D., additional, Mailliez, A., additional, Priou, F., additional, Tredan, O., additional, Dalenc, F., additional, Perrin, C., additional, Timar David, M., additional, Dohollou, N., additional, Teixeira, L., additional, Brocard, F., additional, Arnaud, A., additional, Delaloge, S., additional, Spano, J.-P., additional, Mansi, L., additional, Damian, F., additional, Pedrini, J., additional, Aleixo, S., additional, Hegg, R., additional, Junior, R., additional, Schmidt, M., additional, Wenzel, C., additional, Grischke, E.-M., additional, Just, M., additional, Harbeck, N., additional, Schumacher, C., additional, Peters, U., additional, Fischer, D., additional, Forstbauer, H., additional, Liersch, R., additional, Warner, E., additional, Bouganim, N., additional, Doyle, C., additional, Price Hiller, J., additional, Vandenberg, T., additional, Pavic, M., additional, Robinson, A., additional, Roldan Urgoiti, G., additional, Califaretti, N., additional, Alacacioglu, A., additional, Gumus, M., additional, Yalcin, B., additional, Cicin, I., additional, Kose, F., additional, Uygun, K., additional, Kaplan, M., additional, Cubukcu, E., additional, Harries, M., additional, Miles, D., additional, Doval, D., additional, Gupta, S., additional, Mohapatra, P., additional, Chatterjee, S., additional, Ghadyalpatil, N., additional, Singhal, M., additional, Nag, S., additional, Agarwal, A., additional, Wolf, I., additional, Gal Yam, E., additional, Yerushalmi, R., additional, Peretz, T., additional, Fried, G., additional, Ben Baruch, N., additional, Katz, D., additional, Hamilton, E., additional, Kayali, F., additional, Brufsky, A., additional, Telli, M., additional, Wright, G., additional, Oyola, R., additional, Rakowski, T., additional, Graff, S., additional, Tjulandin, S., additional, Aparicio, A., additional, Ruiz Borrego, M., additional, Merino, L., additional, Guerra Martinez, J., additional, Lopez, E., additional, Yamashita, T., additional, Ohtani, S., additional, Inoue, K., additional, Ito, Y., additional, Niikura, N., additional, Nakayama, T., additional, Sagara, Y., additional, Yanagita, Y., additional, Kamada, Y., additional, Kaneko, K., additional, Nervo, A., additional, Eniu, A., additional, Schenker, M., additional, Priester, P., additional, Melichar, B., additional, Zimovjanova, M., additional, Sormova, P., additional, Sufliarsky, J., additional, Kakalejcik, M., additional, Belbaraka, R., additional, Errihani, H., additional, Le Than, D., additional, Pham, D., additional, Aravantinos, G., additional, Papadimitriou, C., additional, Koumakis, G., additional, Papandreou, C., additional, Podolski, P., additional, and Tabane, K., additional

Published
2021
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16. P-214 Should patients with active gastrointestinal tumors receive thromboprophylaxis to avoid the negative clinical consequences of CAT? Sub-analysis of ACT4CAT study

Author

Tsoukalas, N., primary, Christopoulou, A., additional, Anastopoulou, G., additional, Papandreou, C., additional, Timotheadou, E., additional, Athanasiadis, I., additional, Koumarianou, A., additional, Peroukidis, S., additional, Samelis, G., additional, Psyrri, A., additional, Kapodistrias, N., additional, Nikolakopoulos, A., additional, Andreadis, C., additional, Ardavanis, A., additional, Samantas, E., additional, Bokas, A., additional, Barbounis, V., additional, Kentepozidis, N., additional, Mavroudis, D., additional, Athanasiadis, A., additional, Papakotoulas, P., additional, and Boukovinas, I., additional

Published
2021
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17. Effects of the Mediterranean Diet or Nut Consumption on Gut Microbiota Composition and Fecal Metabolites and their Relationship with Cardiometabolic Risk Factors

Author

Galié, S., García-Gavilán, J., Camacho-Barcía, L., Atzeni, A., Muralidharan, J., Papandreou, C., Arcelin, P., Palau-Galindo, A., Garcia, D., Basora, J., Arias Vasquez, A., Bulló, M., Galié, S., García-Gavilán, J., Camacho-Barcía, L., Atzeni, A., Muralidharan, J., Papandreou, C., Arcelin, P., Palau-Galindo, A., Garcia, D., Basora, J., Arias Vasquez, A., and Bulló, M.

Abstract

Item does not contain fulltext, SCOPE: To examine whether a Mediterranean Diet (MedDiet) compared to the consumption of nuts in the context of a habitual non-MedDiet exerts a greater beneficial effect on gut microbiota and fecal metabolites; thus, contributing to explain major benefits on cardiometabolic risk factors. METHODS AND RESULTS: Fifty adults with Metabolic Syndrome are randomized to a controlled, crossover 2-months dietary-intervention trial with a 1-month wash-out period, following a MedDiet or consuming nuts (50 g day(-1) ). Microbiota composition is assessed by 16S rRNA gene sequencing and metabolites are measured using Nuclear Magnetic Resonance (NMR) and liquid chromatography coupled to triple quadrupole mass spectrometry (LC-qTOF) platforms in a targeted metabolomics approach. Decreased glucose, insulin and the homeostatic model assessment of insulin resistance (HOMA-IR) is observed after the MedDiet compared to the nuts intervention. Relative abundances of Lachnospiraceae NK4A136 and an uncultured genera of Ruminococcaceae are significantly increased after the MedDiet compared to nuts supplementation. Changes in Lachnospiraceae NK4A136 are inversely associated with insulin levels and HOMA-IR, while positively and negatively with changes in cholate and cadaverine, respectively. CONCLUSIONS: Following a MedDiet, rather than nuts, induces a significant increase in Lachnospiraceae NK4A136 and improves the metabolic risk. This genera seems to affect the bile acid metabolism and cadaverine which may account for the improvement in insulin levels.

Published
2021

18. Tricarboxylic acid cycle related-metabolites and risk of atrial fibrillation and heart failure

Author

Universitat Rovira i Virgili, Bulló M; Papandreou C; García-Gavilán J; Ruiz-Canela M; Li J; Guasch-Ferré M; Toledo E; Clish C; Corella D; Estruch R; Ros E; Fitó M; Lee CH; Pierce K; Razquin C; Arós F; Serra-Majem L; Liang L; Martínez-González MA; Hu FB; Salas-Salvadó J, Universitat Rovira i Virgili, and Bulló M; Papandreou C; García-Gavilán J; Ruiz-Canela M; Li J; Guasch-Ferré M; Toledo E; Clish C; Corella D; Estruch R; Ros E; Fitó M; Lee CH; Pierce K; Razquin C; Arós F; Serra-Majem L; Liang L; Martínez-González MA; Hu FB; Salas-Salvadó J

Abstract

Background: Tricarboxylic acid (TCA) cycle deregulation may predispose to cardiovascular diseases, but the role of TCA cycle-related metabolites in the development of atrial fibrillation (AF) and heart failure (HF) remains unexplored. This study sought to investigate the association of TCA cycle-related metabolites with risk of AF and HF. Methods: We used two nested case-control studies within the PREDIMED study. During a mean follow-up for about 10 years, 512 AF and 334 HF incident cases matched by age (±5 years), sex and recruitment center to 616 controls and 433 controls, respectively, were included in this study. Baseline plasma levels of citrate, aconitate, isocitrate, succinate, malate and D/L-2-hydroxyglutarate were measured with liquid chromatography-tandem mass spectrometry. Multivariable conditional logistic regression models were fitted to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for metabolites and the risk of AF or HF. Potential confounders included smoking, family history of premature coronary heart disease, physical activity, alcohol intake, body mass index, intervention groups, dyslipidemia, hypertension, type 2 diabetes and medication use. Results: Comparing extreme quartiles of metabolites, elevated levels of succinate, malate, citrate and D/L-2-hydroxyglutarate were associated with a higher risk of AF [ORQ4 vs. Q1 (95% CI): 1.80 (1.21–2.67), 2.13 (1.45–3.13), 1.87 (1.25–2.81) and 1.95 (1.31–2.90), respectively]. One SD increase in aconitate was directly associated with AF risk [OR (95% CI): 1.16 (1.01–1.34)]. The corresponding ORs (95% CI) for HF comparing extreme quartiles of malate, aconitate, isocitrate and D/L-2-hydroxyglutarate were 2.15 (1.29–3.56), 2.16 (1.25–3.72), 2.63 (1.56–4.44) and 1.82 (1.10–3.04), respectively. The

Published
2021

19. Choline Metabolism and Risk of Atrial Fibrillation and Heart Failure in the PREDIMED Study

Author

Universitat Rovira i Virgili, Papandreou C; Bulló M; Hernández-Alonso P; Ruiz-Canela M; Li J; Guasch-Ferré M; Toledo E; Clish C; Corella D; Estruch R; Ros E; Fitó M; Alonso-Gómez A; Fiol M; Santos-Lozano JM; Serra-Majem L; Liang L; Martínez-González MA; Hu FB; Salas-Salvadó J, Universitat Rovira i Virgili, and Papandreou C; Bulló M; Hernández-Alonso P; Ruiz-Canela M; Li J; Guasch-Ferré M; Toledo E; Clish C; Corella D; Estruch R; Ros E; Fitó M; Alonso-Gómez A; Fiol M; Santos-Lozano JM; Serra-Majem L; Liang L; Martínez-González MA; Hu FB; Salas-Salvadó J

Abstract

© American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com. BACKGROUND: Few studies have examined the associations of trimethylamine-N-oxide (TMAO) and its precursors (choline, betaine, dimethylglycine, and L-carnitine) with the risk of atrial fibrillation (AF) and heart failure (HF). This study sought to investigate these associations. METHODS: Prospective associations of these metabolites with incident AF and HF were examined among participants at high cardiovascular risk in the PREDIMED study (PREvención con DIeta MEDiterránea) after follow-up for about 10 years. Two nested case-control studies were conducted, including 509 AF incident cases matched to 618 controls and 326 HF incident cases matched to 426 controls. Plasma levels of TMAO and its precursors were semi-quantitatively profiled with liquid chromatography tandem mass spectrometry. Odds ratios were estimated with multivariable conditional logistic regression models. RESULTS: After adjustment for classical risk factors and accounting for multiple testing, participants in the highest quartile vs. the lowest quartile of baseline choline and betaine levels had a higher risk of AF [OR (95% CI): 1.85 (1.30-2.63) and 1.57 (1.09-2.24), respectively]. The corresponding OR for AF for extreme quartiles of dimethylglycine was 1.39 (0.99-1.96). One SD increase in log-transformed dimethylglycine was positively associated with AF risk (OR, 1.17; 1.03-1.33). The corresponding ORs for HF for extreme quartiles of choline, betaine, and dimethylglycine were 2.51 (1.57-4.03), 1.65 (1.00-2.71) and 1.65 (1.04-2.61), respectively. TMAO and L-carnitine levels were not associated with AF or HF. CONCLUSIONS: Our findings support the role of the choline metabolic

Published
2021

20. Effects of nutrition on cognitive function in adults with or without cognitive impairment: A systematic review of randomized controlled clinical trials

Author

Universitat Rovira i Virgili, Gutierrez L; Folch A; Rojas M; Cantero JL; Atienza M; Folch J; Camins A; Ruiz A; Papandreou C; Bulló M, Universitat Rovira i Virgili, and Gutierrez L; Folch A; Rojas M; Cantero JL; Atienza M; Folch J; Camins A; Ruiz A; Papandreou C; Bulló M

Abstract

New dietary approaches for the prevention of cognitive impairment are being investigated. However, evidence from dietary interventions is mainly from food and nutrient supplement interventions, with inconsistent results and high heterogeneity between trials. We conducted a comprehensive systematic search of randomized controlled trials (RCTs) published in MEDLINE-Pub- Med, from January 2018 to July 2021, investigating the impact of dietary counseling, as well as food-based and dietary supplement interventions on cognitive function in adults with or without cognitive impairment. Based on the search strategy, 197 eligible publications were used for data abstraction. Finally, 61 articles were included in the analysis. There was reasonable evidence that dietary patterns, as well as food and dietary supplements improved cognitive domains or measures of brain integrity. The Mediterranean diet showed promising results, whereas the role of the DASH diet was not clear. Healthy food consumption improved cognitive function, although the quality of these studies was relatively low. The role of dietary supplements was mixed, with strong evidence of the benefits of polyphenols and combinations of nutrients, but with low evidence for PUFAs, vitamin D, specific protein, amino acids, and other types of supplements. Further well-designed RCTs are needed to guide the development of dietary approaches for the prevention of cognitive impairment.

Published
2021

21. Changes in circulating metabolites during weight loss and weight loss maintenance in relation to cardiometabolic risk

Author

Universitat Rovira i Virgili, Papandreou C; Harrold JA; Hansen TT; Halford JCG; Sjödin A; Bulló M, Universitat Rovira i Virgili, and Papandreou C; Harrold JA; Hansen TT; Halford JCG; Sjödin A; Bulló M

Abstract

(1) Background: There is a substantial lack of knowledge of the biochemical mechanisms by which weight loss and weight regain exert their beneficial and adverse effects, respectively, on cardiometabolic outcomes. We examined associations between changes in circulating metabolites and changes in cardiometabolic risk factors during diet-induced weight loss and weight loss maintenance. (2) Methods: This prospective analysis of data from the Satiety Innovation (SATIN) study involved adults living with overweight and obesity (mean age=47.5). One hundred sixty-two subjects achieving ?8% weight loss during an initial 8-week low-calorie diet (LCD) were included in a 12-week weight loss maintenance period. Circulating metabolites (m=123) were profiled using a targeted multiplatform approach. Data were analyzed using multivariate linear regression models. (3) Results: Decreases in the concentrations of several phosphatidylcholines (PCs), sphingomyelins (SMs), and valine were consistently associated with decreases in total (TChol) and low-density lipoprotein cholesterol (LDL-C) levels during the LCD. Increases in PCs and SMs were significantly associated with increases in TChol and LDL-C during the weight loss maintenance period. Decreases and increases in PCs during LCD and maintenance period, respectively, were associated with decreases in the levels of triglycerides. (4) Conclusions: The results of this study suggest that decreases in circulating PCs and SMs during weight loss and the subsequent weight loss maintenance period may decrease the cardiovascular risk through impacting TChol and LDL-C. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Published
2021

24. Durvalumab alone and durvalumab plus tremelimumab versus chemotherapy in previously untreated patients with unresectable, locally advanced or metastatic urothelial carcinoma (DANUBE): a randomised, open-label, multicentre, phase 3 trial

Author

Powles, T. van der Heijden, M.S. Castellano, D. Galsky, M.D. Loriot, Y. Petrylak, D.P. Ogawa, O. Park, S.H. Lee, J.-L. De Giorgi, U. Bögemann, M. Bamias, A. Eigl, B.J. Gurney, H. Mukherjee, S.D. Fradet, Y. Skoneczna, I. Tsiatas, M. Novikov, A. Suárez, C. Fay, A.P. Duran, I. Necchi, A. Wildsmith, S. He, P. Angra, N. Gupta, A.K. Levin, W. Bellmunt, J. van der Heijden, M.S. Lee, J.L. Eigl, B.J. Mukherjee, S.D. Suarez, C. Westgeest, H. Flechon, A. Ou, Y.-C. Park, I. Matveev, V. Pérez-Valderrama, B. Cheng, S. Frank, S. Anido, U. Hamzaj, A. Retz, M. Sridhar, S. Scagliotti, G.V. Voortman, J. Alekseev, B. Alyasova, A. Komyakov, B. Dumez, H. Pavic, M. Kimura, G. Mizokami, A. Osanto, S. Arranz, J.A. Piersma, D. Shin, S.J. Karyakin, O. Delgado, I. Gonzalez, J.L. Pang, S.-T. Tran, A. Lipatov, O. Su, W.-P. Flaig, T. Alva, A. Park Kyong, H. Kopyltsov, E. Almagro, E. Domenech, M. Chang, Y.-H. Sautois, B. Ravaux, A. Aravantinos, G. Georgoulias, V. Mulder, S. Kim, Y.J. Kater, F. Chevreau, C. Tagawa, S. Zalewski, P. Joly, F. Hatiboglu, G. Gianni, L. Morelli, F. Tambaro, R. Hashimoto, Y. Nosov, A. Font, A. Rodriguez-Vida, A.M. Jones, R. Vasudev, N. Srinivas, S. Zhang, J. Gil, T. Finch, D. Grimm, M.-O. Su, Y.-L. Chowdhury, S. Hocking, C. Plas, E. North, S. Jensen, N.V. Theodore, C. Imkamp, F. Peer, A. Kobayashi, T. Sakai, H. Sassa, N. Yoshimura, K. Aarts, M. Ferreira Castro, A. Topuzov, M. Rodriguez, J.F. Vazquez, F.J. Tsai, Y.-C. Crabb, S. Hussain, S. Bendell, J. Gross-Goupil, M. Gwenaelle, G. Berger, R. Statsenko, G. Evans, L. Drakaki, A. Somer, B. Davis, I. Lynam, J. Borges, G. Dettino, A. Fay, A.P. Martins, G. Zucca, L.E. Agerbaek, M. Kalofonos, H. Rosenbaum, E. Enokida, H. Kikukawa, H. Nishimura, K. Tamada, S. Uemura, M. Lopez, Y. Gietema, J. Slojewski, M. Fernandes, I. Smolin, A. Mazhar, D. Kalebasty, A.R. Carthon, B. Loidl, W. Franke, F. Girotto, G. Alimohamed, N. Macfarlane, R. Pappot, H. Niegisch, G. Mavroudis, D. Sella, A. Porta, C. Ebara, S. Nakamura, M. Obara, W. Okuno, N. Shinohara, N. Sugimoto, M. Suzuki, A. Tokuda, N. Uemura, H. Yamaguchi, A. Ramirez, F. Rozanowski, P. Wiechno, P. Keam, B. Kislov, N. Plaksin, D. Cicin, I. Kumar, S. Galsky, M.D. Petrylak, D.P. Rosales, J. Vaishampayan, U. Culine, S. Papandreou, C. Nara, T. Erman, M. Kreiger, L. Janoski, J. Rosa, D. Siqueira, M. Canil, C. Sengelov, L. Tourani, J.-M. Arai, G. Hashine, K. Kawakita, M. Nakaigawa, N. Nomi, H. Shiina, H. Suzuki, H. Yonese, J. Kuri, R. Macedo, E. Rivera, S. Villalobos Prieto, A. Polakiewicz-Gilowska, A. Zaucha, R. Lopes, F. Ponomarev, R. Pomerantz, M. Shariat, S. Luk, C. Lesniewski-Kmak, K.

Abstract

Background: Survival outcomes are poor for patients with metastatic urothelial carcinoma who receive standard, first-line, platinum-based chemotherapy. We assessed the overall survival of patients who received durvalumab (a PD-L1 inhibitor), with or without tremelimumab (a CTLA-4 inhibitor), as a first-line treatment for metastatic urothelial carcinoma. Methods: DANUBE is an open-label, randomised, controlled, phase 3 trial in patients with untreated, unresectable, locally advanced or metastatic urothelial carcinoma, conducted at 224 academic research centres, hospitals, and oncology clinics in 23 countries. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0 or 1. We randomly assigned patients (1:1:1) to receive durvalumab monotherapy (1500 mg) administered intravenously every 4 weeks; durvalumab (1500 mg) plus tremelimumab (75 mg) administered intravenously every 4 weeks for up to four doses, followed by durvalumab maintenance (1500 mg) every 4 weeks; or standard-of-care chemotherapy (gemcitabine plus cisplatin or gemcitabine plus carboplatin, depending on cisplatin eligibility) administered intravenously for up to six cycles. Randomisation was done through an interactive voice–web response system, with stratification by cisplatin eligibility, PD-L1 status, and presence or absence of liver metastases, lung metastases, or both. The coprimary endpoints were overall survival compared between the durvalumab monotherapy versus chemotherapy groups in the population of patients with high PD-L1 expression (the high PD-L1 population) and between the durvalumab plus tremelimumab versus chemotherapy groups in the intention-to-treat population (all randomly assigned patients). The study has completed enrolment and the final analysis of overall survival is reported. The trial is registered with ClinicalTrials.gov, NCT02516241, and the EU Clinical Trials Register, EudraCT number 2015-001633-24. Findings: Between Nov 24, 2015, and March 21, 2017, we randomly assigned 1032 patients to receive durvalumab (n=346), durvalumab plus tremelimumab (n=342), or chemotherapy (n=344). At data cutoff (Jan 27, 2020), median follow-up for survival was 41·2 months (IQR 37·9–43·2) for all patients. In the high PD-L1 population, median overall survival was 14·4 months (95% CI 10·4–17·3) in the durvalumab monotherapy group (n=209) versus 12·1 months (10·4–15·0) in the chemotherapy group (n=207; hazard ratio 0·89, 95% CI 0·71–1·11; p=0·30). In the intention-to-treat population, median overall survival was 15·1 months (13·1–18·0) in the durvalumab plus tremelimumab group versus 12·1 months (10·9–14·0) in the chemotherapy group (0·85, 95% CI 0·72–1·02; p=0·075). In the safety population, grade 3 or 4 treatment-related adverse events occurred in 47 (14%) of 345 patients in the durvalumab group, 93 (27%) of 340 patients in the durvalumab plus tremelimumab group, and in 188 (60%) of 313 patients in the chemotherapy group. The most common grade 3 or 4 treatment-related adverse event was increased lipase in the durvalumab group (seven [2%] of 345 patients) and in the durvalumab plus tremelimumab group (16 [5%] of 340 patients), and neutropenia in the chemotherapy group (66 [21%] of 313 patients). Serious treatment-related adverse events occurred in 30 (9%) of 345 patients in the durvalumab group, 78 (23%) of 340 patients in the durvalumab plus tremelimumab group, and 50 (16%) of 313 patients in the chemotherapy group. Deaths due to study drug toxicity were reported in two (1%) patients in the durvalumab group (acute hepatic failure and hepatitis), two (1%) patients in the durvalumab plus tremelimumab group (septic shock and pneumonitis), and one (

Published
2020

25. Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): overall survival and updated results of a randomised, double-blind, phase 3 trial

Author

Petrylak, D.P. de Wit, R. Chi, K.N. Drakaki, A. Sternberg, C.N. Nishiyama, H. Castellano, D. Hussain, S.A. Fléchon, A. Bamias, A. Yu, E.Y. van der Heijden, M.S. Matsubara, N. Alekseev, B. Necchi, A. Géczi, L. Ou, Y.-C. Coskun, H.S. Su, W.-P. Bedke, J. Gakis, G. Percent, I.J. Lee, J.-L. Tucci, M. Semenov, A. Laestadius, F. Peer, A. Tortora, G. Safina, S. Garcia del Muro, X. Rodriguez-Vida, A. Cicin, I. Harputluoglu, H. Tagawa, S.T. Vaishampayan, U. Aragon-Ching, J.B. Hamid, O. Liepa, A.M. Wijayawardana, S. Russo, F. Walgren, R.A. Zimmermann, A.H. Hozak, R.R. Bell-McGuinn, K.M. Powles, T. Wong, S.-L.S. Tan, T.H. Hovey, E.J. Clay, T.D. Wan Ng, S.S. Rutten, A. Machiels, J.-P. Dumez, H. Cheng, S.Y.-S. Ferrario, C. Sengeloev, L. Jensen, N.V. Thibault, C. Laguerre, B. Joly, F. Culine, S. Becht, C. Niegisch, G. Stöckle, M. Grimm, M.-O. Schwentner, C.A. Schultze-Seemann, W. Kalofonos, H. Mavroudis, D. Papandreou, C. Karavasilis, V. Révész, J. Rosenbaum, E. Leibowitz-Amit, R. Kejzman, D. Sarid, D. Scagliotti, G.V. Bracarda, S. Massari, F. Osawa, T. Miyajima, N. Shinohara, N. Fukuta, F. Ohyama, C. Obara, W. Yamashita, S. Tomita, Y. Kawai, K. Fukasawa, S. Oyama, M. Yonese, J. Nagata, M. Uemura, M. Nishimura, K. Kawakita, M. Tsunemori, H. Hashine, K. Inokuchi, J. Yokomizo, A. Nagamori, S. Lee, H.J. Park, S.H. Rha, S.Y. Kim, Y.J. Lee, Y.-G. Vazquez Cortés, L. Lorena Urzua Flores, C. Blaisse, R.J.B. Erdkamp, F.L.G. Aarts, M.J.B. Wojcik-Tomaszewska, J. Tomczak, P. Sikora-Kupis, B. Schenker, M. Herzal, A.A. Udrea, A.A. Karlov, P. Fomkin, R. Gajate Borau, P. Grande, E. Delgado Mignorance, J.I. Su, Y.-L. Li, J.-R. Lin, C.-L. Lin, C.-C. Yeh, S.-P. Erman, M. Urun, Y. Golovko, Y. Bondarenko, I. Sinielnikov, I. Crabb, S.J. Syndikus, I. Huddart, R. Sundar, S. Chowdhury, S. Sarwar, N. Flaig, T.W. Pan, C.X. Schwarz, J.K. Cultrera, J.L. Acs, P.I. Hainsworth, J.D. Herms, B.T. Lawler, W.E. Lowe, T.E.

Abstract

Background: Ramucirumab—an IgG1 vascular endothelial growth factor receptor 2 antagonist—plus docetaxel was previously reported to improve progression-free survival in platinum-refractory, advanced urothelial carcinoma. Here, we report the secondary endpoint of overall survival results for the RANGE trial. Methods: We did a randomised, double-blind, phase 3 trial in patients with advanced or metastatic urothelial carcinoma who progressed during or after platinum-based chemotherapy. Patients were enrolled from 124 investigative sites (hospitals, clinics, and academic centres) in 23 countries. Previous treatment with one immune checkpoint inhibitor was permitted. Patients were randomly assigned (1:1) using an interactive web response system to receive intravenous ramucirumab 10 mg/kg or placebo 10 mg/kg volume equivalent followed by intravenous docetaxel 75 mg/m2 (60 mg/m2 in Korea, Taiwan, and Japan) on day 1 of a 21-day cycle. Treatment continued until disease progression, unacceptable toxicity, or other discontinuation criteria were met. Randomisation was stratified by geographical region, Eastern Cooperative Oncology Group performance status at baseline, and visceral metastasis. Progression-free survival (the primary endpoint) and overall survival (a key secondary endpoint) were assessed in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT02426125; patient enrolment is complete and the last patient on treatment is being followed up for safety issues. Findings: Between July 20, 2015, and April 4, 2017, 530 patients were randomly allocated to ramucirumab plus docetaxel (n=263) or placebo plus docetaxel (n=267) and comprised the intention-to-treat population. At database lock (March 21, 2018) for the final overall survival analysis, median follow-up was 7·4 months (IQR 3·5–13·9). In our sensitivity analysis of investigator-assessed progression-free survival at the overall survival database lock, median progression-free survival remained significantly improved with ramucirumab compared with placebo (4·1 months [95% CI 3·3–4·8] vs 2·8 months [2·6–2·9]; HR 0·696 [95% CI 0·573–0·845]; p=0·0002). Median overall survival was 9·4 months (95% CI 7·9–11·4) in the ramucirumab group versus 7·9 months (7·0–9·3) in the placebo group (stratified HR 0·887 [95% CI 0·724–1·086]; p=0·25). Grade 3 or worse treatment-related treatment-emergent adverse events in 5% or more of patients and with an incidence more than 2% higher with ramucirumab than with placebo were febrile neutropenia (24 [9%] of 258 patients in the ramucirumab group vs 16 [6%] of 265 patients in the placebo group) and neutropenia (17 [7%] of 258 vs six [2%] of 265). Serious adverse events were similar between groups (112 [43%] of 258 patients in the ramucirumab group vs 107 [40%] of 265 patients in the placebo group). Adverse events related to study treatment and leading to death occurred in eight (3%) patients in the ramucirumab group versus five (2%) patients in the placebo group. Interpretation: Additional follow-up supports that ramucirumab plus docetaxel significantly improves progression-free survival, without a significant improvement in overall survival, for patients with platinum-refractory advanced urothelial carcinoma. Clinically meaningful benefit might be restricted in an unselected population. Funding: Eli Lilly and Company. © 2020 Elsevier Ltd

Published
2020

26. High plasma glutamate and a low glutamine-to-glutamate ratio are associated with increased risk of heart Failure but Not Atrial Fibrillation in the Prevención con Dieta Mediterránea (PREDIMED) Study

Author

Universitat Rovira i Virgili, Papandreou C; Hernández-Alonso P; Bulló M; Ruiz-Canela M; Li J; Guasch-Ferré M; Toledo E; Clish C; Corella D; Estruch R; Cofán M; Fitó M; Razquin C; Arós F; Fiol M; Santos-Lozano JM; Serra-Majem L; Liang L; Martínez-González MA; Hu FB; Salas-Salvadó J, Universitat Rovira i Virgili, and Papandreou C; Hernández-Alonso P; Bulló M; Ruiz-Canela M; Li J; Guasch-Ferré M; Toledo E; Clish C; Corella D; Estruch R; Cofán M; Fitó M; Razquin C; Arós F; Fiol M; Santos-Lozano JM; Serra-Majem L; Liang L; Martínez-González MA; Hu FB; Salas-Salvadó J

Abstract

© 2020 The Author(s). Published by Oxford University Press on behalf of the American Society for Nutrition. Background: Although the association between glutamate and glutamine in relation to cardiometabolic disorders has been evaluated, the role of these metabolites in the development of atrial fibrillation (AF) and heart failure (HF) remains unknown. Objectives: We examined associations of glutamate, glutamine, and the glutamine-to-glutamate ratio with AF and HF incidence in a Mediterranean population at high cardiovascular disease (CVD) risk. Methods: The present study used 2 nested case-control studies within the PREDIMED (Prevención con Dieta Mediterránea) study. During ∼10 y of follow-up, there were 509 AF incident cases matched to 618 controls and 326 HF incident cases matched to 426 controls. Plasma concentrations of glutamate and glutamine were semiquantitatively profiled with LC-tandem MS. ORs were estimated with multivariable conditional logistic regression models. Results: In fully adjusted models, per 1-SD increment, glutamate was associated with a 29% (95% CI: 1.08, 1.54) increased risk of HF and glutamine-to-glutamate ratio with a 20% (95% CI: 0.67, 0.94) decreased risk. Glutamine-to-glutamate ratio was also inversely associated with HF risk (OR per 1-SD increment: 0.80; 95% CI: 0.67, 0.94) when comparing extreme quartiles. Higher glutamate concentrations were associated with a worse cardiometabolic risk profile, whereas a higher glutamine-to-glutamate ratio was associated with a better cardiometabolic risk profile. No associations between the concentrations of these metabolites and AF were observed. Conclusions: Our findings suggest that high plasma glutamate concentrations possibly resulting from alterations in the glutamate-glutamine cycle may contribu

Published
2020

27. Plasma Metabolomics Profiles are Associated with the Amount and Source of Protein Intake: A Metabolomics Approach within the PREDIMED Study

Author

Universitat Rovira i Virgili, Hernández-Alonso P, Becerra-Tomás N, Papandreou C, Bulló M, Guasch-Ferré M, Toledo E, Ruiz-Canela M, Clish CB, Corella D, Dennis C, Deik A, Wang DD, Razquin C, Drouin-Chartier JP, Estruch R, Ros E, Fitó M, Arós F, Fiol M, Serra-Majem L, Liang L, Martínez-González MA, Hu FB, Salas-Salvadó J, Universitat Rovira i Virgili, and Hernández-Alonso P, Becerra-Tomás N, Papandreou C, Bulló M, Guasch-Ferré M, Toledo E, Ruiz-Canela M, Clish CB, Corella D, Dennis C, Deik A, Wang DD, Razquin C, Drouin-Chartier JP, Estruch R, Ros E, Fitó M, Arós F, Fiol M, Serra-Majem L, Liang L, Martínez-González MA, Hu FB, Salas-Salvadó J

Abstract

The plasma metabolomics profiles of protein intake has been rarely investigated. We aimed to identify the distinct plasma metabolomics profiles associated with overall intakes of protein as well as with intakes from animal and plant protein sources.Cross-sectional analysis using data from 1,833 participants at high risk of cardiovascular disease. Plasma metabolomics analysis was performed using LC-MS. Associations between 385 identified metabolites and the intake of total, animal protein (AP) and plant protein (PP), and plant-to-animal ratio (PR) were assessed using elastic net continuous regression analyses. A double 10-cross-validation (CV) procedure was used and Pearson correlations coefficients between multi-metabolite weighted models and reported protein intake in each pair of training-validation datasets were calculated. A wide set of metabolites was consistently associated with each protein source evaluated. These metabolites mainly consisted of amino acids and their derivatives, acylcarnitines, different organic acids and lipid species. Few metabolites overlapped among protein sources (i.e. C14:0 SM, C20:4 carnitine, GABA and allantoin) but none of them towards the same direction. Regarding AP and PP approaches, C20:4 carnitine and dimethylglycine were positively associated with PP but negatively associated with AP. However, allantoin, C14:0 SM, C38:7 PE plasmalogen, GABA, metronidazole and trigonelline (N-methylnicotinate) behaved contrary. Ten-CV Pearson correlations coefficients between self-reported protein intake and plasma metabolomics profiles ranged from 0.21 for PR to 0.32 for total protein.Different sets of metabolites were associated with total, animal and plant protein intake. Further studies are needed to assess the contribution of these metabolites

Published
2020

30. 1825P Prevention and prophylaxis (thromboprophylaxis - ACT) of cancer associated thrombosis (CAT) in high risk oncology patients: ACT4CAT

Author

Tsoukalas, N.G., primary, Christopoulou, A.N., additional, Papandreou, C., additional, Kapodistrias, N., additional, Koumarianou, A., additional, Peroukidis, S., additional, Kalofonos, H., additional, Samelis, G.F., additional, Andreadis, C., additional, Ardavanis, A., additional, Samantas, E., additional, Bokas, A., additional, Ligdas, A., additional, Athanasiadis, I., additional, Barbounis, V., additional, Kentepozidis, N., additional, Mavroudis, D., additional, Athanasiadis, A., additional, Papakotoulas, P., additional, and Boukovinas, I., additional

Published
2020
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32. Safety and tolerability of subcutaneous trastuzumab for the adjuvant treatment of human epidermal growth factor receptor 2-positive early breast cancer: SafeHer phase III study's primary analysis of 2573 patients

Author

Gligorov, J, Ataseven, B, Verrill, M, de Laurentiis, M, Jung, K, Azim, H, Al-Sakaff, N, Lauer, S, Shing, M, Pivot, X, Koroveshi, D, Bouzid, K, Casalnuovo, M, Cascallar, D, Korbenfeld, E, Bastick, P, Beith, J, Colosimo, M, Friedlander, M, Ganju, V, Green, M, Patterson, K, Redfern, A, Richardson, G, Ceric, T, Gordana, K, Beato, C, Ferrari, M, Hegg, R, Helena, V, Ismael, G, Lessa, A, Mano, M, Morelle, A, Nogueira, J, Timcheva, K, Tomova, A, Tsakova, M, Zlatareva-Petrova, A, Asselah, J, Assi, H, Brezden-Masley, C, Chia, S, Freedman, O, Harb, M, Joy, A, Kulkarni, S, Prady, C, Gaete, A, Matamala, L, Torres, R, Yanez, E, Franco, S, Urrego, M, Gugic, D, Vrbanec, D, Melichar, B, Prausova, J, Vyzula, R, Pilarte, R, Leon, M, Munoz, R, Ramos, G, Azeem, H, Aziz, A, El Zawahry, H, Osegueda, F, Alexandre, J, Artignan, X, Barletta, H, Beguier, E, Berdah, J, Marty, C, Bollet, M, Bourgeois, H, Bressac, C, Burki, F, Campone, M, Coeffic, D, Cojocarasu, O, Dagada, C, Dalenc, F, Del Piano, F, Desauw, C, Desmoulins, I, Dohollou, N, Egreteau, J, Ferrero, J, Foa, C, Garidi, R, Gasnault, L, Guardiola, E, Hamizi, S, Jarcau, R, Jacquin, J, Jaubert, D, Jolimoy, G, Mineur, H, Largillier, R, Leduc, B, Martin, P, Melis, A, Monge, J, Moullet, I, Mousseau, M, Nguyen, S, Orfeuvre, H, Petit, T, Priou, F, Bach, I, Simon, H, Stefani, L, Uwer, L, Youssef, A, Aktas, B, von der Assen, A, Augustin, D, Balser, C, Bauer, L, Bechtner, C, Beyer, G, Brucker, C, Buckner, U, Busch, S, Christensen, B, Deryal, M, Farrokh, A, Faust, E, Friedrichs, K, Graf, H, Griesshammer, M, Grischke, E, Hanle, C, Heider, A, Henschen, S, Hesse, T, Jackisch, C, Kisro, J, Kohler, A, Kuemmel, S, Lampe, D, Lantzsch, T, Latos, K, Lex, B, Liedtke, C, Luedders, D, Maintz, C, Muller, V, Overkamp, F, Park-Simon, T, Paul, M, Prechtl, A, Ringsdorf, U, Runnebaum, I, Ruth, S, Salat, C, Scheffen, I, Schilling, J, Schmatloch, S, Schmidt, M, Schneeweiss, A, Schrader, I, Seipelt, G, Simon, E, Stefek, A, Stickeler, E, Thill, M, Tio, J, Tuczek, A, Warm, M, Weigel, M, Wischnik, A, Wojcinski, S, Ziegler-Lohr, K, Aravantinos, G, Ardavanis, A, Fountzilas, G, Gogas, H, Kakolyris, S, Mavroudis, D, Papadimitriou, C, Papandreou, C, Papazisis, K, Castro, H, Hernandez-Monroy, C, Ngan, R, Yeo, W, Bittner, N, Boer, K, Csejtei, A, Horvath, Z, Kocsis, J, Mangel, L, Mezei, K, Nagy, Z, Szanto, J, Atmakusuma, D, Fadjari, H, Kurnianda, D, Prayogo, N, Tanggo, E, Coate, L, Hennessy, B, Kelly, C, Martin, M, Nasim, S, O'Connor, M, Aieta, M, Allegrini, G, Amadori, D, Bidoli, P, Biti, G, Bordonaro, R, Bottini, A, Carterni, G, Cavanna, L, Cazzaniga, M, Cognetti, F, Contu, A, Cruciani, G, Donadio, M, Falcone, A, Farci, D, Forcignano, R, Frassoldati, A, Gaion, F, Gamucci, T, Giotta, F, Livi, L, Lorusso, V, Maiello, E, Marchetti, P, Mariani, G, Mion, M, Moscetti, L, Musolino, A, Pazzola, A, Pedrazzoli, P, Pigi, A, de Placido, S, Caremoli, E, Santoro, A, Tienghi, A, Ahn, J, Lee, K, Lee, S, Seo, J, Sohn, J, Cesas, A, Juozaityte, E, Cheah, N, Chong, F, Devi, B, Phua, V, Teoh, D, Ching, L, Yusof, M, Corona, J, Dominguez, A, Mendoza, R, Hernandez, C, Ramiro, A, Santos, J, Espinosa, P, Villarreal Garza, C, Errihani, H, Bakker, S, van den Berkmortel, F, Blaisse, R, Huinink, D, van den Bosch, J, Braun, J, Dercksen, M, Droogendijk, H, Erdkamp, F, Haringhuizen, A, de Jongh, F, Kok, T, Los, M, Madretsma, S, Terwogt, J, van der Padt, A, van Rossum-Schornagel, Q, Smilde, T, de Valk, B, van der Velden, A, van Warmerdam, L, van de Wouw, A, North, R, Kersten, C, Mjaaland, I, Wist, E, Aziz, Z, Masood, N, Rashid, K, Shah, M, Alcedo, J, Aleman, D, Neciosup, S, Reategui, R, Valdiviezo, N, Vera, L, Fernando, G, Roque, F, Strebel, H, Krzemieniecki, K, Litwiniuk, M, Mruk, A, Pienkowski, T, Sawrycki, P, Slomian, G, Tomczak, P, Afonso, N, Cardoso, F, Damasceno, M, Nave, M, Badulescu, F, Ciule, L, Curescu, S, Eniu, A, Filip, D, Grecea, D, Jinga, D, Lungulescu, D, Oprean, C, Stanculeanu, D, Turdean, M, Dvornichenko, V, Emelyanov, S, Lichinitser, M, Manikhas, A, Sakaeva, D, Shirinkin, V, Stroyakovskiy, D, Abulkhair, O, Zekri, J, Filipovic, S, Kovcin, V, Nedovic, J, Pesic, J, Vasovic, S, Ng, R, Bystricky, B, Leskova, J, Mardiak, J, Misurova, E, Wagnerova, M, Takac, I, Demetriou, G, Dreosti, L, Govender, P, Jordaan, J, Veersamy, P, Romero, J, Lopez, N, Arias, C, Chacon, J, Aramburo, A, Morales, L, Garcia, M, Estevez, L, Garcia-Palomo Perez, A, Garcia Saenz, J, Garcia Sanchis, L, Cubells, L, Cortijo, L, Santiago, S, De Aranguiz, B, Manas, J, Gallego, P, Cussac, A, Ferrandiz, C, Garrido, M, Alvarez, P, Vega, J, Del Prado, P, Janez, N, Murillo, S, Rosales, A, Jaso, L, Fernandez, I, Martorell, A, Carrion, R, Simon, S, Alcibar, A, Lorenzo, J, Garcia, V, Asensio, T, Maicas, M, Villanueva Silva, M, Killander, F, Svensson, J, Fehr, M, Hauser, N, Muller, A, Pagani, O, Passmann-Kegel, H, Popescu, R, Rabaglio, M, Rauch, D, Schlatter, C, Zaman, K, Chang, T, Huang, C, Wang, H, Yu, J, Bandidwattanawong, C, Maneechavakajorn, J, Seetalarom, K, Dejthevaporn, T, Somwangprasert, A, Vongsaisuwon, M, Akbulut, H, Altundag, K, Arican, A, Bozcuk, H, Eralp, Y, Idris, M, Isikdogan, A, Senol, C, Sevinc, A, Uygun, K, Yucel, E, Yucel, I, Yumuk, F, Shparyk, Y, Voitko, N, Jaloudi, M, Adams, J, Agrawal, R, Ahmed, S, Alhasso, A, Allerton, R, Anwar, S, Archer, C, Ashford, R, Barraclough, L, Bertelli, G, Bishop, J, Branson, T, Butt, M, Chakrabarti, A, Chakraborti, P, Churn, M, Crowley, C, Davis, R, Dhadda, A, Eldeeb, H, Fraser, J, Hall, J, Hickish, T, Hogg, M, Howe, T, Joffe, J, Kelleher, M, Kelly, S, Kendall, A, Kristeleit, H, Lumsden, G, Macmillan, C, Macpherson, I, Malik, Z, Mithal, N, Neal, A, Panwar, U, Proctor, A, Proctor, S, Raj, S, Rehman, S, Sandri, I, Scatchard, K, Sherwin, E, Sims, E, Singer, J, Smith, S, Tahir, S, Taylor, W, Tsalic, M, Wardley, A, Waters, S, Wheatley, D, Wright, K, Yuille, F, Alonso, I, Artagaveytia, N, Rodriguez, R, Arbona, E, Garcia, Y, Lion, L, Marcano, D, Van Thuan, T, Gligorov J., Ataseven B., Verrill M., de Laurentiis M., Jung K. H., Azim H. A., Al-Sakaff N., Lauer S., Shing M., Pivot X., Koroveshi D., Bouzid K., Casalnuovo M., Cascallar D., Korbenfeld E. P., Bastick P., Beith J., Colosimo M., Friedlander M., Ganju V., Green M., Patterson K., Redfern A., Richardson G., Ceric T., Gordana K., Beato C. A., Ferrari M., Hegg R., Helena V., Ismael G. F., Lessa A. E., Mano M., Morelle A., Nogueira J. A., Timcheva K., Tomova A., Tsakova M., Zlatareva-Petrova A., Asselah J., Assi H., Brezden-Masley C., Chia S., Freedman O., Harb M., Joy A. A., Kulkarni S., Prady C., Gaete A. A. A., Matamala L., Torres R., Yanez E., Franco S., Urrego M., Gugic D., Vrbanec D., Melichar B., Prausova J., Vyzula R., Pilarte R. G., Leon M. I., Munoz R., Ramos G., Azeem H. A., Aziz A. A., El Zawahry H., Osegueda F. R., Alexandre J., Artignan X., Barletta H., Beguier E., Berdah J. -F., Marty C. B., Bollet M., Bourgeois H., Bressac C., Burki F., Campone M., Coeffic D., Cojocarasu O. Z., Dagada C., Dalenc F., Del Piano F., Desauw C., Desmoulins I., Dohollou N., Egreteau J., Ferrero J. -M., Foa C., Garidi R., Gasnault L., Guardiola E., Hamizi S., Jarcau R., Jacquin J. -P., Jaubert D., Jolimoy G., Mineur H. L., Largillier R., Leduc B., Martin P., Melis A., Monge J., Moullet I., Mousseau M., Nguyen S., Orfeuvre H., Petit T., Priou F., Bach I. S., Simon H., Stefani L., Uwer L., Youssef A., Aktas B., von der Assen A., Augustin D., Balser C., Bauer L. -E., Bechtner C., Beyer G., Brucker C., Buckner U., Busch S., Christensen B., Deryal M., Farrokh A., Faust E., Friedrichs K., Graf H., Griesshammer M., Grischke E. -M., Hanle C., Heider A., Henschen S., Hesse T., Jackisch C., Kisro J., Kohler A., Kuemmel S., Lampe D., Lantzsch T., Latos K., Lex B., Liedtke C., Luedders D., Maintz C., Muller V., Overkamp F., Park-Simon T. -W., Paul M., Prechtl A., Ringsdorf U., Runnebaum I., Ruth S., Salat C., Scheffen I., Schilling J., Schmatloch S., Schmidt M., Schneeweiss A., Schrader I., Seipelt G., Simon E., Stefek A., Stickeler E., Thill M., Tio J., Tuczek A., Warm M., Weigel M., Wischnik A., Wojcinski S., Ziegler-Lohr K., Aravantinos G., Ardavanis A., Fountzilas G., Gogas H., Kakolyris S., Mavroudis D., Papadimitriou C., Papandreou C., Papazisis K., Castro H., Hernandez-Monroy C. E., Ngan R., Yeo W., Bittner N., Boer K., Csejtei A., Horvath Z., Kocsis J., Mangel L. C., Mezei K., Nagy Z., Szanto J., Atmakusuma D., Fadjari H., Kurnianda D., Prayogo N., Tanggo E. H., Coate L., Hennessy B., Kelly C., Martin M., Nasim S., O'Connor M., Aieta M., Allegrini G., Amadori D., Bidoli P., Biti G., Bordonaro R., Bottini A., Carterni G., Cavanna L., Cazzaniga M., Cognetti F., Contu A., Cruciani G., Donadio M., Falcone A., Farci D., Forcignano R. C., Frassoldati A., Gaion F., Gamucci T., Giotta F., Livi L., Lorusso V., Maiello E., Marchetti P., Mariani G., Mion M., Moscetti L., Musolino A., Pazzola A., Pedrazzoli P., Pigi A., de Placido S., Caremoli E. R., Santoro A., Tienghi A., Ahn J. -S., Lee K. S., Lee S. H., Seo J. H., Sohn J. -H., Cesas A., Juozaityte E., Cheah N. L. C., Chong F. L. T., Devi B. C. R., Phua V., Teoh D., Ching L. W., Yusof M., Corona J., Dominguez A., Mendoza R. L. G., Hernandez C. A., Ramiro A. J., Santos J. M., Espinosa P. M., Villarreal Garza C. M., Errihani H., Bakker S., van den Berkmortel F., Blaisse R. J. B., Huinink D. T. B., van den Bosch J., Braun J. J., Dercksen M. W., Droogendijk H., Erdkamp F., Haringhuizen A., de Jongh F. E., Kok T. C., Los M., Madretsma S., Terwogt J. M. M., van der Padt A., van Rossum-Schornagel Q. C., Smilde T. J., de Valk B., van der Velden A., van Warmerdam L., van de Wouw A. J., North R., Kersten C., Mjaaland I., Wist E., Aziz Z., Masood N., Rashid K., Shah M., Alcedo J. C., Aleman D., Neciosup S., Reategui R., Valdiviezo N., Vera L., Fernando G., Roque F., Strebel H. M., Krzemieniecki K., Litwiniuk M., Mruk A., Pienkowski T., Sawrycki P., Slomian G., Tomczak P., Afonso N., Cardoso F., Damasceno M., Nave M., Badulescu F., Ciule L., Curescu S., Eniu A., Filip D., Grecea D., Jinga D. -C., Lungulescu D., Oprean C. M., Stanculeanu D. L., Turdean M., Dvornichenko V., Emelyanov S., Lichinitser M., Manikhas A., Sakaeva D., Shirinkin V., Stroyakovskiy D., Abulkhair O., Zekri J., Filipovic S., Kovcin V., Nedovic J., Pesic J., Vasovic S., Ng R., Bystricky B., Leskova J., Mardiak J., Misurova E., Wagnerova M., Takac I., Demetriou G. S., Dreosti L., Govender P., Jordaan J. P., Veersamy P., Romero J. L. A., Lopez N. B., Arias C. C., Chacon J., Aramburo A. F., Morales L. A. F., Garcia M., Estevez L. G., Garcia-Palomo Perez A., Garcia Saenz J. A., Garcia Sanchis L., Cubells L. G., Cortijo L. G., Santiago S. G., De Aranguiz B. H. F., Manas J. J. I., Gallego P. J., Cussac A. L., Ferrandiz C. L., Garrido M. L., Alvarez P. L., Vega J. M. L., Del Prado P. M., Janez N. M., Murillo S. M., Rosales A. M., Jaso L. M., Fernandez I. P., Martorell A. P., Carrion R. P., Simon S. P., Alcibar A. P., Lorenzo J. P., Garcia V. Q., Asensio T. R. Y. C., Maicas M. D. T., Villanueva Silva M. J., Killander F., Svensson J. H., Fehr M., Hauser N., Muller A., Pagani O., Passmann-Kegel H., Popescu R., Rabaglio M., Rauch D., Schlatter C., Zaman K., Chang T. -W., Huang C. -S., Wang H. -C., Yu J. -C., Bandidwattanawong C., Maneechavakajorn J., Seetalarom K., Dejthevaporn T. S., Somwangprasert A., Vongsaisuwon M., Akbulut H., Altundag K., Arican A., Bozcuk H., Eralp Y., Idris M., Isikdogan A., Senol C. H., Sevinc A., Uygun K., Yucel E., Yucel I., Yumuk F., Shparyk Y., Voitko N., Jaloudi M., Adams J., Agrawal R., Ahmed S., Alhasso A., Allerton R., Anwar S., Archer C., Ashford R., Barraclough L., Bertelli G., Bishop J., Branson T., Butt M., Chakrabarti A., Chakraborti P., Churn M., Crowley C., Davis R., Dhadda A., Eldeeb H., Fraser J., Hall J., Hickish T., Hogg M., Howe T., Joffe J., Kelleher M., Kelly S., Kendall A., Kristeleit H., Lumsden G., Macmillan C., MacPherson I., Malik Z., Mithal N., Neal A., Panwar U., Proctor A., Proctor S. J., Raj S., Rehman S., Sandri I., Scatchard K., Sherwin E., Sims E., Singer J., Smith S., Tahir S., Taylor W., Tsalic M., Wardley A., Waters S., Wheatley D., Wright K., Yuille F., Alonso I., Artagaveytia N., Rodriguez R., Arbona E., Garcia Y., Lion L., Marcano D., Van Thuan T., Gligorov, J, Ataseven, B, Verrill, M, de Laurentiis, M, Jung, K, Azim, H, Al-Sakaff, N, Lauer, S, Shing, M, Pivot, X, Koroveshi, D, Bouzid, K, Casalnuovo, M, Cascallar, D, Korbenfeld, E, Bastick, P, Beith, J, Colosimo, M, Friedlander, M, Ganju, V, Green, M, Patterson, K, Redfern, A, Richardson, G, Ceric, T, Gordana, K, Beato, C, Ferrari, M, Hegg, R, Helena, V, Ismael, G, Lessa, A, Mano, M, Morelle, A, Nogueira, J, Timcheva, K, Tomova, A, Tsakova, M, Zlatareva-Petrova, A, Asselah, J, Assi, H, Brezden-Masley, C, Chia, S, Freedman, O, Harb, M, Joy, A, Kulkarni, S, Prady, C, Gaete, A, Matamala, L, Torres, R, Yanez, E, Franco, S, Urrego, M, Gugic, D, Vrbanec, D, Melichar, B, Prausova, J, Vyzula, R, Pilarte, R, Leon, M, Munoz, R, Ramos, G, Azeem, H, Aziz, A, El Zawahry, H, Osegueda, F, Alexandre, J, Artignan, X, Barletta, H, Beguier, E, Berdah, J, Marty, C, Bollet, M, Bourgeois, H, Bressac, C, Burki, F, Campone, M, Coeffic, D, Cojocarasu, O, Dagada, C, Dalenc, F, Del Piano, F, Desauw, C, Desmoulins, I, Dohollou, N, Egreteau, J, Ferrero, J, Foa, C, Garidi, R, Gasnault, L, Guardiola, E, Hamizi, S, Jarcau, R, Jacquin, J, Jaubert, D, Jolimoy, G, Mineur, H, Largillier, R, Leduc, B, Martin, P, Melis, A, Monge, J, Moullet, I, Mousseau, M, Nguyen, S, Orfeuvre, H, Petit, T, Priou, F, Bach, I, Simon, H, Stefani, L, Uwer, L, Youssef, A, Aktas, B, von der Assen, A, Augustin, D, Balser, C, Bauer, L, Bechtner, C, Beyer, G, Brucker, C, Buckner, U, Busch, S, Christensen, B, Deryal, M, Farrokh, A, Faust, E, Friedrichs, K, Graf, H, Griesshammer, M, Grischke, E, Hanle, C, Heider, A, Henschen, S, Hesse, T, Jackisch, C, Kisro, J, Kohler, A, Kuemmel, S, Lampe, D, Lantzsch, T, Latos, K, Lex, B, Liedtke, C, Luedders, D, Maintz, C, Muller, V, Overkamp, F, Park-Simon, T, Paul, M, Prechtl, A, Ringsdorf, U, Runnebaum, I, Ruth, S, Salat, C, Scheffen, I, Schilling, J, Schmatloch, S, Schmidt, M, Schneeweiss, A, Schrader, I, Seipelt, G, Simon, E, Stefek, A, Stickeler, E, Thill, M, Tio, J, Tuczek, A, Warm, M, Weigel, M, Wischnik, A, Wojcinski, S, Ziegler-Lohr, K, Aravantinos, G, Ardavanis, A, Fountzilas, G, Gogas, H, Kakolyris, S, Mavroudis, D, Papadimitriou, C, Papandreou, C, Papazisis, K, Castro, H, Hernandez-Monroy, C, Ngan, R, Yeo, W, Bittner, N, Boer, K, Csejtei, A, Horvath, Z, Kocsis, J, Mangel, L, Mezei, K, Nagy, Z, Szanto, J, Atmakusuma, D, Fadjari, H, Kurnianda, D, Prayogo, N, Tanggo, E, Coate, L, Hennessy, B, Kelly, C, Martin, M, Nasim, S, O'Connor, M, Aieta, M, Allegrini, G, Amadori, D, Bidoli, P, Biti, G, Bordonaro, R, Bottini, A, Carterni, G, Cavanna, L, Cazzaniga, M, Cognetti, F, Contu, A, Cruciani, G, Donadio, M, Falcone, A, Farci, D, Forcignano, R, Frassoldati, A, Gaion, F, Gamucci, T, Giotta, F, Livi, L, Lorusso, V, Maiello, E, Marchetti, P, Mariani, G, Mion, M, Moscetti, L, Musolino, A, Pazzola, A, Pedrazzoli, P, Pigi, A, de Placido, S, Caremoli, E, Santoro, A, Tienghi, A, Ahn, J, Lee, K, Lee, S, Seo, J, Sohn, J, Cesas, A, Juozaityte, E, Cheah, N, Chong, F, Devi, B, Phua, V, Teoh, D, Ching, L, Yusof, M, Corona, J, Dominguez, A, Mendoza, R, Hernandez, C, Ramiro, A, Santos, J, Espinosa, P, Villarreal Garza, C, Errihani, H, Bakker, S, van den Berkmortel, F, Blaisse, R, Huinink, D, van den Bosch, J, Braun, J, Dercksen, M, Droogendijk, H, Erdkamp, F, Haringhuizen, A, de Jongh, F, Kok, T, Los, M, Madretsma, S, Terwogt, J, van der Padt, A, van Rossum-Schornagel, Q, Smilde, T, de Valk, B, van der Velden, A, van Warmerdam, L, van de Wouw, A, North, R, Kersten, C, Mjaaland, I, Wist, E, Aziz, Z, Masood, N, Rashid, K, Shah, M, Alcedo, J, Aleman, D, Neciosup, S, Reategui, R, Valdiviezo, N, Vera, L, Fernando, G, Roque, F, Strebel, H, Krzemieniecki, K, Litwiniuk, M, Mruk, A, Pienkowski, T, Sawrycki, P, Slomian, G, Tomczak, P, Afonso, N, Cardoso, F, Damasceno, M, Nave, M, Badulescu, F, Ciule, L, Curescu, S, Eniu, A, Filip, D, Grecea, D, Jinga, D, Lungulescu, D, Oprean, C, Stanculeanu, D, Turdean, M, Dvornichenko, V, Emelyanov, S, Lichinitser, M, Manikhas, A, Sakaeva, D, Shirinkin, V, Stroyakovskiy, D, Abulkhair, O, Zekri, J, Filipovic, S, Kovcin, V, Nedovic, J, Pesic, J, Vasovic, S, Ng, R, Bystricky, B, Leskova, J, Mardiak, J, Misurova, E, Wagnerova, M, Takac, I, Demetriou, G, Dreosti, L, Govender, P, Jordaan, J, Veersamy, P, Romero, J, Lopez, N, Arias, C, Chacon, J, Aramburo, A, Morales, L, Garcia, M, Estevez, L, Garcia-Palomo Perez, A, Garcia Saenz, J, Garcia Sanchis, L, Cubells, L, Cortijo, L, Santiago, S, De Aranguiz, B, Manas, J, Gallego, P, Cussac, A, Ferrandiz, C, Garrido, M, Alvarez, P, Vega, J, Del Prado, P, Janez, N, Murillo, S, Rosales, A, Jaso, L, Fernandez, I, Martorell, A, Carrion, R, Simon, S, Alcibar, A, Lorenzo, J, Garcia, V, Asensio, T, Maicas, M, Villanueva Silva, M, Killander, F, Svensson, J, Fehr, M, Hauser, N, Muller, A, Pagani, O, Passmann-Kegel, H, Popescu, R, Rabaglio, M, Rauch, D, Schlatter, C, Zaman, K, Chang, T, Huang, C, Wang, H, Yu, J, Bandidwattanawong, C, Maneechavakajorn, J, Seetalarom, K, Dejthevaporn, T, Somwangprasert, A, Vongsaisuwon, M, Akbulut, H, Altundag, K, Arican, A, Bozcuk, H, Eralp, Y, Idris, M, Isikdogan, A, Senol, C, Sevinc, A, Uygun, K, Yucel, E, Yucel, I, Yumuk, F, Shparyk, Y, Voitko, N, Jaloudi, M, Adams, J, Agrawal, R, Ahmed, S, Alhasso, A, Allerton, R, Anwar, S, Archer, C, Ashford, R, Barraclough, L, Bertelli, G, Bishop, J, Branson, T, Butt, M, Chakrabarti, A, Chakraborti, P, Churn, M, Crowley, C, Davis, R, Dhadda, A, Eldeeb, H, Fraser, J, Hall, J, Hickish, T, Hogg, M, Howe, T, Joffe, J, Kelleher, M, Kelly, S, Kendall, A, Kristeleit, H, Lumsden, G, Macmillan, C, Macpherson, I, Malik, Z, Mithal, N, Neal, A, Panwar, U, Proctor, A, Proctor, S, Raj, S, Rehman, S, Sandri, I, Scatchard, K, Sherwin, E, Sims, E, Singer, J, Smith, S, Tahir, S, Taylor, W, Tsalic, M, Wardley, A, Waters, S, Wheatley, D, Wright, K, Yuille, F, Alonso, I, Artagaveytia, N, Rodriguez, R, Arbona, E, Garcia, Y, Lion, L, Marcano, D, Van Thuan, T, Gligorov J., Ataseven B., Verrill M., de Laurentiis M., Jung K. H., Azim H. A., Al-Sakaff N., Lauer S., Shing M., Pivot X., Koroveshi D., Bouzid K., Casalnuovo M., Cascallar D., Korbenfeld E. P., Bastick P., Beith J., Colosimo M., Friedlander M., Ganju V., Green M., Patterson K., Redfern A., Richardson G., Ceric T., Gordana K., Beato C. A., Ferrari M., Hegg R., Helena V., Ismael G. F., Lessa A. E., Mano M., Morelle A., Nogueira J. A., Timcheva K., Tomova A., Tsakova M., Zlatareva-Petrova A., Asselah J., Assi H., Brezden-Masley C., Chia S., Freedman O., Harb M., Joy A. A., Kulkarni S., Prady C., Gaete A. A. A., Matamala L., Torres R., Yanez E., Franco S., Urrego M., Gugic D., Vrbanec D., Melichar B., Prausova J., Vyzula R., Pilarte R. G., Leon M. I., Munoz R., Ramos G., Azeem H. A., Aziz A. A., El Zawahry H., Osegueda F. R., Alexandre J., Artignan X., Barletta H., Beguier E., Berdah J. -F., Marty C. B., Bollet M., Bourgeois H., Bressac C., Burki F., Campone M., Coeffic D., Cojocarasu O. Z., Dagada C., Dalenc F., Del Piano F., Desauw C., Desmoulins I., Dohollou N., Egreteau J., Ferrero J. -M., Foa C., Garidi R., Gasnault L., Guardiola E., Hamizi S., Jarcau R., Jacquin J. -P., Jaubert D., Jolimoy G., Mineur H. L., Largillier R., Leduc B., Martin P., Melis A., Monge J., Moullet I., Mousseau M., Nguyen S., Orfeuvre H., Petit T., Priou F., Bach I. S., Simon H., Stefani L., Uwer L., Youssef A., Aktas B., von der Assen A., Augustin D., Balser C., Bauer L. -E., Bechtner C., Beyer G., Brucker C., Buckner U., Busch S., Christensen B., Deryal M., Farrokh A., Faust E., Friedrichs K., Graf H., Griesshammer M., Grischke E. -M., Hanle C., Heider A., Henschen S., Hesse T., Jackisch C., Kisro J., Kohler A., Kuemmel S., Lampe D., Lantzsch T., Latos K., Lex B., Liedtke C., Luedders D., Maintz C., Muller V., Overkamp F., Park-Simon T. -W., Paul M., Prechtl A., Ringsdorf U., Runnebaum I., Ruth S., Salat C., Scheffen I., Schilling J., Schmatloch S., Schmidt M., Schneeweiss A., Schrader I., Seipelt G., Simon E., Stefek A., Stickeler E., Thill M., Tio J., Tuczek A., Warm M., Weigel M., Wischnik A., Wojcinski S., Ziegler-Lohr K., Aravantinos G., Ardavanis A., Fountzilas G., Gogas H., Kakolyris S., Mavroudis D., Papadimitriou C., Papandreou C., Papazisis K., Castro H., Hernandez-Monroy C. E., Ngan R., Yeo W., Bittner N., Boer K., Csejtei A., Horvath Z., Kocsis J., Mangel L. C., Mezei K., Nagy Z., Szanto J., Atmakusuma D., Fadjari H., Kurnianda D., Prayogo N., Tanggo E. H., Coate L., Hennessy B., Kelly C., Martin M., Nasim S., O'Connor M., Aieta M., Allegrini G., Amadori D., Bidoli P., Biti G., Bordonaro R., Bottini A., Carterni G., Cavanna L., Cazzaniga M., Cognetti F., Contu A., Cruciani G., Donadio M., Falcone A., Farci D., Forcignano R. C., Frassoldati A., Gaion F., Gamucci T., Giotta F., Livi L., Lorusso V., Maiello E., Marchetti P., Mariani G., Mion M., Moscetti L., Musolino A., Pazzola A., Pedrazzoli P., Pigi A., de Placido S., Caremoli E. R., Santoro A., Tienghi A., Ahn J. -S., Lee K. S., Lee S. H., Seo J. H., Sohn J. -H., Cesas A., Juozaityte E., Cheah N. L. C., Chong F. L. T., Devi B. C. R., Phua V., Teoh D., Ching L. W., Yusof M., Corona J., Dominguez A., Mendoza R. L. G., Hernandez C. A., Ramiro A. J., Santos J. M., Espinosa P. M., Villarreal Garza C. M., Errihani H., Bakker S., van den Berkmortel F., Blaisse R. J. B., Huinink D. T. B., van den Bosch J., Braun J. J., Dercksen M. W., Droogendijk H., Erdkamp F., Haringhuizen A., de Jongh F. E., Kok T. C., Los M., Madretsma S., Terwogt J. M. M., van der Padt A., van Rossum-Schornagel Q. C., Smilde T. J., de Valk B., van der Velden A., van Warmerdam L., van de Wouw A. J., North R., Kersten C., Mjaaland I., Wist E., Aziz Z., Masood N., Rashid K., Shah M., Alcedo J. C., Aleman D., Neciosup S., Reategui R., Valdiviezo N., Vera L., Fernando G., Roque F., Strebel H. M., Krzemieniecki K., Litwiniuk M., Mruk A., Pienkowski T., Sawrycki P., Slomian G., Tomczak P., Afonso N., Cardoso F., Damasceno M., Nave M., Badulescu F., Ciule L., Curescu S., Eniu A., Filip D., Grecea D., Jinga D. -C., Lungulescu D., Oprean C. M., Stanculeanu D. L., Turdean M., Dvornichenko V., Emelyanov S., Lichinitser M., Manikhas A., Sakaeva D., Shirinkin V., Stroyakovskiy D., Abulkhair O., Zekri J., Filipovic S., Kovcin V., Nedovic J., Pesic J., Vasovic S., Ng R., Bystricky B., Leskova J., Mardiak J., Misurova E., Wagnerova M., Takac I., Demetriou G. S., Dreosti L., Govender P., Jordaan J. P., Veersamy P., Romero J. L. A., Lopez N. B., Arias C. C., Chacon J., Aramburo A. F., Morales L. A. F., Garcia M., Estevez L. G., Garcia-Palomo Perez A., Garcia Saenz J. A., Garcia Sanchis L., Cubells L. G., Cortijo L. G., Santiago S. G., De Aranguiz B. H. F., Manas J. J. I., Gallego P. J., Cussac A. L., Ferrandiz C. L., Garrido M. L., Alvarez P. L., Vega J. M. L., Del Prado P. M., Janez N. M., Murillo S. M., Rosales A. M., Jaso L. M., Fernandez I. P., Martorell A. P., Carrion R. P., Simon S. P., Alcibar A. P., Lorenzo J. P., Garcia V. Q., Asensio T. R. Y. C., Maicas M. D. T., Villanueva Silva M. J., Killander F., Svensson J. H., Fehr M., Hauser N., Muller A., Pagani O., Passmann-Kegel H., Popescu R., Rabaglio M., Rauch D., Schlatter C., Zaman K., Chang T. -W., Huang C. -S., Wang H. -C., Yu J. -C., Bandidwattanawong C., Maneechavakajorn J., Seetalarom K., Dejthevaporn T. S., Somwangprasert A., Vongsaisuwon M., Akbulut H., Altundag K., Arican A., Bozcuk H., Eralp Y., Idris M., Isikdogan A., Senol C. H., Sevinc A., Uygun K., Yucel E., Yucel I., Yumuk F., Shparyk Y., Voitko N., Jaloudi M., Adams J., Agrawal R., Ahmed S., Alhasso A., Allerton R., Anwar S., Archer C., Ashford R., Barraclough L., Bertelli G., Bishop J., Branson T., Butt M., Chakrabarti A., Chakraborti P., Churn M., Crowley C., Davis R., Dhadda A., Eldeeb H., Fraser J., Hall J., Hickish T., Hogg M., Howe T., Joffe J., Kelleher M., Kelly S., Kendall A., Kristeleit H., Lumsden G., Macmillan C., MacPherson I., Malik Z., Mithal N., Neal A., Panwar U., Proctor A., Proctor S. J., Raj S., Rehman S., Sandri I., Scatchard K., Sherwin E., Sims E., Singer J., Smith S., Tahir S., Taylor W., Tsalic M., Wardley A., Waters S., Wheatley D., Wright K., Yuille F., Alonso I., Artagaveytia N., Rodriguez R., Arbona E., Garcia Y., Lion L., Marcano D., and Van Thuan T.

Abstract

Aim To assess the safety and tolerability of adjuvant subcutaneous trastuzumab (Herceptin® SC, H SC), delivered from an H SC Vial via hand-held syringe (Cohort A) or single-use injection device (Cohort B), with or without chemotherapy, for human epidermal growth factor receptor 2 (HER2)-positive stage I to IIIC early breast cancer (EBC) in the phase III SafeHer study (NCT01566721). Methods Patients received 600 mg fixed-dose H SC every 3 weeks for 18 cycles. The chemotherapy partner was at the investigators' discretion (H SC monotherapy was limited to ≤10% of the population). Data from the first H SC dose until 28 days (plus a 5-day window) after the last dose are presented. Results are descriptive. Results In the overall population, 2282/2573 patients (88.7%) experienced adverse events (AEs). Of the above, 128 (5.0%) patients experienced AEs leading to study drug discontinuation; 596 (23.2%) experienced grade ≥ 3 AEs and 326 (12.7%) experienced serious AEs. Grade ≥ 3 cardiac disorders were reported in 24 patients (0.9%), including congestive heart failure in eight (0.3%). As expected, the AE rates varied according to the timing of chemotherapy in both cohorts, with higher rates in concurrent versus sequential chemotherapy subgroups. In the concurrent chemotherapy subgroup, AEs were more common during the actual period of concurrent chemotherapy compared with the period when patients did not receive concurrent chemotherapy. Conclusion SafeHer confirms the safety and tolerability of the H SC 600 mg fixed dose for 1 year (every 3 weeks for 18 cycles) as adjuvant therapy with concurrent or sequential chemotherapy for HER2-positive EBC. These primary analysis results are consistent with the known safety profile for intravenous H and H SC.

Published
2017

35. Trebananib or placebo plus carboplatin and paclitaxel as first-line treatment for advanced ovarian cancer (TRINOVA-3/ENGOT-ov2/GOG-3001): a randomised, double-blind, phase 3 trial

Author

Vergote, I. Scambia, G. O'Malley, D.M. Van Calster, B. Park, S.-Y. del Campo, J.M. Meier, W. Bamias, A. Colombo, N. Wenham, R.M. Covens, A. Marth, C. Raza Mirza, M. Kroep, J.R. Ma, H. Pickett, C.A. Monk, B.J. Park, S.Y. Song, Y.S. Makarova, Y. Trinidad, J. Ngan, H.Y.S. Aravantinos, G. Nam, J.-H. Gorbunova, V. Krikunova, L. Bae, D.-S. Arija, J.A.A. Mirza, M.R. Zamagni, C. Papandreou, C. Raspagliesi, F. Lisyanskaya, A. Benzaquen, A.O. Tognon, G. Ortega, E. Herraez, A.C. Buscema, J. Green, A. Burger, R. Sakaeva, D. Sanchez, A.R. Ghamande, S. King, L. Petru, E. Peen, U. Takeuchi, S. Ushijima, K. Martin, A.G. Kamelle, S. Carney, M. Forget, F. Bentley, J. Sehouli, J. Zola, P. Kato, H. Fadeeva, N. Gotovkin, E. Vladimirov, V. Marin, M.R. Alia, E.G. Shahin, M. Bhoola, S. Tewari, K. Anderson, D. Honhon, B. Pelgrims, J.G. Oza, A. Jimenez, J.G.-D. Hansen, V. Benjamin, I. Renard, V. Van den Bulck, H. Haenle, C. Koumakis, G. Yokota, H. Popov, V. Bradley, W. Wenham, R. Reid, R. McNamara, D. Friedman, R. Barlin, J. Spirtos, N. Chapman, J. Sevelda, P. Huizing, M. Lamot, C. Goffin, F. Hondt, L.D. Covens, A. Spadafora, S. Rautenberg, B. Reimer, T. Möbus, V. Hilpert, F. Gropp-Meier, M. Savarese, A. Pignata, S. Verderame, F. Mizuno, M. Takano, H. Ottevanger, P. Velasco, A.P. Palacio-Vazquez, I. Law, A. McIntyre, K. Teneriello, M. Fields, A. Lentz, S. Street, D. Schwartz, B. Mannel, R. Lim, P. Pulaski, H. Janni, W. Zorr, A. Karck, U. Cheng, A.C.K. Sorio, R. Gridelli, C. Aoki, D. Oishi, T. Hirashima, Y. Boere, I. Ferrer, E.F. Braly, P. Wilks, S. Lee, C. Schilder, J. Veljovich, D. Secord, A. Davis, K. Rojas-Espaillat, L. Lele, S. DePasquale, S. Squatrito, R. Schauer, C. Dirix, L. Vuylsteke, P. Joosens, E. Provencher, D. Lueck, H.-J. Hein, A. Burges, A. Canzler, U. Park-Simon, T.-W. Griesinger, F. Gadducci, A. Alabiso, O. Okamoto, A. Sawasaki, T. Saito, T. Ibañez, A.H. Calomeni, C. Spillman, M. Choksi, J. Taylor, N. Muller, C. Moore, D. DiSilvestro, P. Cunningham, M. Rose, P. Oppelt, P. Verhoeven, D. Graas, M.-P. Ghatage, P. Tonkin, K. Kurzeder, C. Schnappauf, B. Müller, V. Schmalzrie, H. Kalofonos, H. Bruzzone, M. Kroep, J. Diaz, C.C. Garcia, J.M. Polo, S.H. Garrison, M. Rocconi, R. Andrews, S. Bristow, R. McHale, M. Basil, J. Houck III, W. Bell, M. Cosin, J. Modesitt, S. Kendrick, J. Wade III, J. Wong, C. Evans, A. Buekers, T. Vanderkwaak, T. Ferriss, J. Darus, C. DAndre, S. Higgins, R. Monk, B. Bakkum-Gamez, J. DeMars, L. Van Le, L. Puls, L. Trehan, S. LaPolla, J. Michelson, E.D. Merchant, J. Peterson, C. Reid, G. Seago, D. Zweizig, S. Gajewski, W. Panwalkar, A. Leikermoser, R. Bogner, G. Debruyne, P. D'hondt, R. Berteloot, P. Kerger, J. Biagi, J. Castonguay, V. Welch, S. Muhic, A. Heubner, M. Grischke, E.-M. Rack, B. Fleisch, M. Lordick, F. Pectasides, D. Ho, W.M. Selvaggi, L. Vasquez, F.M. Villanueva, W.O.B. Alavez, A.M. Kessels, L. Bertran, A.S. Fernandez, C.M. Fabregat, M.B. Del Prete, S. Elkas, J. Cecchi, G. Kumar, P. Huh, W. Messing, M. Karimi, M. Kelley, A. Edraki, B. Mutch, D. Leiserowitz, G. Anderson, J. Lentz, S. Chambers, S. Morris, R. Waggoner, S. Gordon, A. Method, M. Johnson, P. Lord, R. Drake, J. Sivarajan, K. Midathada, M. Rice, K. Wadsworth, T. Pavelka, J. Edwards, R. Miller, D.S. Ford, P.L. Hurteau, J. Bender, D. Schimp, V. Creasman, W. Lerner, R. Chamberlain, D. Kueck, A. McDonald, J. Malad, S. Robinson-Bennett, B. Davidson, S. Krivak, T. Lestingi, T. Arango, H. Berard, P. Finkelstein, K. Gaur, R. Krasner, C. Ueland, F. Talmage, L. Yamada, S. Sutton, G. Potkul, R. Prasad-Hayes, M. Osborne, J. Celano, P. Thigpen, J. Sharma, S. Schilder, R. Tammela, J. Kemeny, M. Brown, A. Eisenhauer, E. Williams, J. Rowland, K. Nahum, K. Burke, J. Dar, Z. Fleming, N. Gibb, R. Guirguis, A. Herzog, T. John, V. Kumar, S. Kamat, A. Kassar, M. Leitao, M. Levine, L. Mendez, L. Patel, D. Berry, E. Warshal, D. Wolf, J. Zarwan, C. Collins, Y. Spitzer, G. Miller, B. Einstein, M. TRINOVA-3/ENGOT-ov2/GOG-3001 investigators

Abstract

Background: Angiopoietin 1 and 2 regulate angiogenesis and vascular remodelling by interacting with the tyrosine kinase receptor Tie2, and inhibition of angiogenesis has shown promise in the treatment of ovarian cancer. We aimed to assess whether trebananib, a peptibody that inhibits binding of angiopoietin 1 and 2 to Tie2, improved progression-free survival when added to carboplatin and paclitaxel as first-line therapy in advanced epithelial ovarian, primary fallopian tube, or peritoneal cancer in a phase 3 clinical trial. Methods: TRINOVA-3, a multicentre, multinational, phase 3, double-blind study, was done at 206 investigational sites (hospitals and cancer centres)in 14 countries. Eligible patients were aged 18 years or older with biopsy-confirmed International Federation of Gynecology and Obstetrics (FIGO)stage III to IV epithelial ovarian, primary peritoneal, or fallopian tube cancers, and an ECOG performance status of 0 or 1. Eligible patients were randomly assigned (2:1)using a permuted block method (block size of six patients)to receive six cycles of paclitaxel (175 mg/m2)and carboplatin (area under the serum concentration-time curve 5 or 6)every 3 weeks, plus weekly intravenous trebananib 15 mg/kg or placebo. Maintenance therapy with trebananib or placebo continued for up to 18 additional months. The primary endpoint was progression-free survival, as assessed by the investigators, in the intention-to-treat population. Safety analyses included patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01493505, and is complete. Findings: Between Jan 30, 2012, and Feb 25, 2014, 1164 patients were screened and 1015 eligible patients were randomly allocated to treatment (678 to trebananib and 337 to placebo). After a median follow-up of 27·4 months (IQR 17·7–34·2), 626 patients had progression-free survival events (405 [60%]of 678 in the trebananib group and 221 [66%]of 337 in the placebo group). Median progression-free survival did not differ between the trebananib group (15·9 months [15·0–17·6])and the placebo group (15·0 months [12·6–16·1])groups (hazard ratio 0·93 [95% CI 0·79–1·09]; p=0·36). 512 (76%)of 675 patients in the trebananib group and 237 (71%)of 336 in the placebo group had grade 3 or worse treatment-emergent adverse events; of which the most common events were neutropenia (trebananib 238 [35%]vs placebo 126 [38%])anaemia (76 [11%]vs 40 [12%]), and leucopenia (81 [12%]vs 35 [10%]). 269 (40%)patients in the trebananib group and 104 (31%)in the placebo group had serious adverse events. Two fatal adverse events in the trebananib group were considered related to trebananib, paclitaxel, and carboplatin (lung infection and neutropenic colitis); two were considered to be related to paclitaxel and carboplatin (general physical health deterioration and platelet count decreased). No treatment-related fatal adverse events occurred in the placebo group. Interpretation: Trebananib plus carboplatin and paclitaxel did not improve progression-free survival as first-line treatment for advanced ovarian cancer. The combination of trebananib plus carboplatin and paclitaxel did not produce new safety signals. These results show that trebananib in combination with carboplatin and paclitaxel is minimally effective in this patient population. Funding: Amgen. © 2019 Elsevier Ltd

Published
2019

36. Metabolites related to purine catabolism and risk of type 2 diabetes incidence; modifying effects of the TCF7L2-rs7903146 polymorphism

Author

Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Salas-Salvadó J, Hu FB, Martínez-González MA, Rosique N, Serra-Majem L, Arós F, Fitó M, Ros E, Estruch R, Corella D, Clish C, Razquin C, Guasch-Ferré M, Yu E, Ruiz-Canela M, Zheng Y, Bulló M, Liang L, Li J, Papandreou C, Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Salas-Salvadó J, Hu FB, Martínez-González MA, Rosique N, Serra-Majem L, Arós F, Fitó M, Ros E, Estruch R, Corella D, Clish C, Razquin C, Guasch-Ferré M, Yu E, Ruiz-Canela M, Zheng Y, Bulló M, Liang L, Li J, and Papandreou C

Abstract

© 2019, The Author(s). Studies examining associations between purine metabolites and type 2 diabetes (T2D) are limited. We prospectively examined associations between plasma levels of purine metabolites with T2D risk and the modifying effects of transcription factor-7-like-2 (TCF7L2) rs7903146 polymorphism on these associations. This is a case-cohort design study within the PREDIMED study, with 251 incident T2D cases and a random sample of 694 participants (641 non-cases and 53 overlapping cases) without T2D at baseline (median follow-up: 3.8 years). Metabolites were semi-quantitatively profiled with LC-MS/MS. Cox regression analysis revealed that high plasma allantoin levels, including allantoin-to-uric acid ratio and high xanthine-to-hypoxanthine ratio were inversely and positively associated with T2D risk, respectively, independently of classical risk factors. Elevated plasma xanthine and inosine levels were associated with a higher T2D risk in homozygous carriers of the TCF7L2-rs7903146 T-allele. The potential mechanisms linking the aforementioned purine metabolites and T2D risk must be also further investigated.

Published
2019

37. Plasma metabolites predict both insulin resistance and incident type 2 diabetes: a metabolomics approach within the Prevención con Dieta Mediterránea (PREDIMED) study

Author

Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Papandreou C, Bulló M, Ruiz-Canela M, Dennis C, Deik A, Wang D, Guasch-Ferré M, Yu E, Razquin C, Corella D, Estruch R, Ros E, Fitó M, Fiol M, Liang L, Hernández-Alonso P, Clish CB, Martínez-González MA, Hu FB, Salas-Salvadó J, Bioquímica i Biotecnologia, Universitat Rovira i Virgili, and Papandreou C, Bulló M, Ruiz-Canela M, Dennis C, Deik A, Wang D, Guasch-Ferré M, Yu E, Razquin C, Corella D, Estruch R, Ros E, Fitó M, Fiol M, Liang L, Hernández-Alonso P, Clish CB, Martínez-González MA, Hu FB, Salas-Salvadó J

Abstract

Insulin resistance is a complex metabolic disorder and is often associated with type 2 diabetes (T2D).The aim of this study was to test whether baseline metabolites can additionally improve the prediction of insulin resistance beyond classical risk factors. Furthermore, we examined whether a multimetabolite model predicting insulin resistance in nondiabetics can also predict incident T2D.We used a case-cohort study nested within the Prevención con Dieta Mediterránea (PREDIMED) trial in subsets of 700, 500, and 256 participants without T2D at baseline and 1 and 3 y. Fasting plasma metabolites were semiquantitatively profiled with liquid chromatography-tandem mass spectrometry. We assessed associations between metabolite concentrations and the homeostasis model of insulin resistance (HOMA-IR) through the use of elastic net regression analysis. We subsequently examined associations between the baseline HOMA-IR-related multimetabolite model and T2D incidence through the use of weighted Cox proportional hazard models.We identified a set of baseline metabolites associated with HOMA-IR. One-year changes in metabolites were also significantly associated with HOMA-IR. The area under the curve was significantly greater for the model containing the classical risk factors and metabolites together compared with classical risk factors alone at baseline [0.81 (95% CI: 0.79, 0.84) compared with 0.69 (95% CI: 0.66, 0.73)] and during a 1-y period [0.69 (95% CI: 0.66, 0.72) compared with 0.57 (95% CI: 0.53, 0.62)]. The variance in HOMA-IR explained by the combination of metabolites and classical risk factors was also higher in all time periods. The estimated HRs for incident T2D in the multimetabolite score (model 3) predicting high HOMA-IR (median value or higher) or HOMA-IR (continuous)

Published
2019

38. Association Between Fatty Acids of Blood Cell Membranes and Incidence of Coronary Heart Disease

Author

Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Papandreou C, Sala-Vila A, Galié S, Muralidharan J, Estruch R, Fitó M, Razquin C, Corella D, Ros E, Timiraos J, Lapetra J, Serra-Majem L, Carlos S, Castañer O, Asensio EM, Salas-Salvadó J, Bulló M, Bioquímica i Biotecnologia, Universitat Rovira i Virgili, and Papandreou C, Sala-Vila A, Galié S, Muralidharan J, Estruch R, Fitó M, Razquin C, Corella D, Ros E, Timiraos J, Lapetra J, Serra-Majem L, Carlos S, Castañer O, Asensio EM, Salas-Salvadó J, Bulló M

Abstract

Objective- To examine the associations between baseline levels of fatty acids in blood cell membranes and their 1-year changes with the incidence of coronary heart disease (CHD) in older adults at high cardiovascular disease risk. Approach and Results- This is a case-control study nested in the PREDIMED trial (Prevención con Dieta Mediterránea), with 136 CHD cases and 272 controls (matched on age, sex, body mass index, intervention group, and time of permanence in the study to the time event). We used gas chromatography to measure the proportion of 22 fatty acids in blood cell membranes at baseline and after 1 year. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% CIs. After adjustment for classical CHD risk factors and multiple testing, 1 SD increase in baseline levels of C22:0, C24:0 and the sum of individual very long chain saturated fatty acids was associated with 56% (OR, 0.44 [95% CI, 0.28-0.69]), 59% (OR, 0.41 [95% CI, 0.25-0.65]), and 55% (OR, 0.45 [95% CI, 0.29-0.70]) a decreased odds of developing CHD, respectively. Baseline C20:1n9 was associated with higher odds of CHD (OR, 1.58 [95% CI, 1.25-2.00]). Conclusions- Higher levels of C22:0 and C24:0 were associated with a lower CHD incidence, whereas higher levels of C20:1n9 were associated with a higher risk. This study adds to the growing body of evidence suggesting potential differences in the cardiovascular disease effects of different types of circulating saturated fatty acids.

Published
2019

39. Isotemporal substitution of inactive time with physical activity and time in bed: cross-sectional associations with cardiometabolic health in the PREDIMED-Plus study.

Author

Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Galmes-Panades AM, Varela-Mato V, Konieczna J, Wärnberg J, Martínez-González MÁ, Salas-Salvadó J, Corella D, Schröder H, Vioque J, Alonso-Gómez ÁM, Martínez JA, Serra-Majem L, Estruch R, Tinahones FJ, Lapetra J, Pintó X, Tur JA, Garcia-Rios A, Riquelme-Gallego B, Gaforio JJ, Matía-Martín P, Daimiel L, Micó Pérez RM, Vidal J, Vázquez C, Ros E, Garcia-Arellano A, Díaz-López A, Asensio EM, Castañer O, Fiol F, Mira-Castejón LA, Moreno Rodríguez A, Benavente-Marín JC, Abete I, Tomaino L, Casas R, Barón López FJ, Fernández-García JC, Santos-Lozano JM, Galera A, Mascaró CM, Razquin C, Papandreou C, Portoles O, Pérez-Vega KA, Fiol M, Compañ-Gabucio L, Vaquero-Luna J, Ruiz-Canela M, Becerra-Tomás N, Fitó M, Romaguera D, Bioquímica i Biotecnologia, Universitat Rovira i Virgili, and Galmes-Panades AM, Varela-Mato V, Konieczna J, Wärnberg J, Martínez-González MÁ, Salas-Salvadó J, Corella D, Schröder H, Vioque J, Alonso-Gómez ÁM, Martínez JA, Serra-Majem L, Estruch R, Tinahones FJ, Lapetra J, Pintó X, Tur JA, Garcia-Rios A, Riquelme-Gallego B, Gaforio JJ, Matía-Martín P, Daimiel L, Micó Pérez RM, Vidal J, Vázquez C, Ros E, Garcia-Arellano A, Díaz-López A, Asensio EM, Castañer O, Fiol F, Mira-Castejón LA, Moreno Rodríguez A, Benavente-Marín JC, Abete I, Tomaino L, Casas R, Barón López FJ, Fernández-García JC, Santos-Lozano JM, Galera A, Mascaró CM, Razquin C, Papandreou C, Portoles O, Pérez-Vega KA, Fiol M, Compañ-Gabucio L, Vaquero-Luna J, Ruiz-Canela M, Becerra-Tomás N, Fitó M, Romaguera D

Abstract

This study explored the association between inactive time and measures of adiposity, clinical parameters, obesity, type 2 diabetes and metabolic syndrome components. It further examined the impact of reallocating inactive time to time in bed, light physical activity (LPA) or moderate-to-vigorous physical activity (MVPA) on cardio-metabolic risk factors, including measures of adiposity and body composition, biochemical parameters and blood pressure in older adults.This is a cross-sectional analysis of baseline data from 2189 Caucasian men and women (age 55-75?years, BMI 27-40 Kg/m2) from the PREDIMED-Plus study (http://www.predimedplus.com/). All participants had ?3 components of the metabolic syndrome. Inactive time, physical activity and time in bed were objectively determined using triaxial accelerometers GENEActiv during 7?days (ActivInsights Ltd., Kimbolton, United Kingdom). Multiple adjusted linear and logistic regression models were used. Isotemporal substitution regression modelling was performed to assess the relationship of replacing the amount of time spent in one activity for another, on each outcome, including measures of adiposity and body composition, biochemical parameters and blood pressure in older adults.Inactive time was associated with indicators of obesity and the metabolic syndrome. Reallocating 30?min per day of inactive time to 30?min per day of time in bed was associated with lower BMI, waist circumference and glycated hemoglobin (HbA1c) (all p-values

Published
2019

40. Long Daytime Napping Is Associated with Increased Adiposity and Type 2 Diabetes in an Elderly Population with Metabolic Syndrome.

Author

Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Papandreou C, Díaz-López A, Babio N, Martínez-González MA, Bulló M, Corella D, Fitó M, Romaguera D, Vioque J, Alonso-Gómez ÁM, Wärnberg J, Martínez AJ, Serra-Majem L, Estruch R, Fernández-García JC, Lapetra J, Pintó X, Tur JA, Garcia-Rios A, Bueno-Cavanillas A, Delgado-Rodríguez M, Matía-Martín P, Daimiel L, Martín-Sánchez V, Vidal J, Vázquez C, Ros E, Buil-Cosiales P, Becerra-Tomas N, Martinez-Lacruz R, Schröder H, Konieczna J, Garcia-de-la-Hera M, Moreno-Rodriguez A, Barón-López J, Pérez-Farinós N, Abete I, Bautista-Castaño I, Casas R, Muñoz-Garach A, Santos-Lozano JM, Trias F, Gallardo-Alfaro L, Ruiz-Canela M, Barragan R, Goday A, Galmés-Panadés AM, González-Botella A, Vaquero-Luna J, Toledo E, Castañer O, Salas-Salvadó J, Bioquímica i Biotecnologia, Universitat Rovira i Virgili, and Papandreou C, Díaz-López A, Babio N, Martínez-González MA, Bulló M, Corella D, Fitó M, Romaguera D, Vioque J, Alonso-Gómez ÁM, Wärnberg J, Martínez AJ, Serra-Majem L, Estruch R, Fernández-García JC, Lapetra J, Pintó X, Tur JA, Garcia-Rios A, Bueno-Cavanillas A, Delgado-Rodríguez M, Matía-Martín P, Daimiel L, Martín-Sánchez V, Vidal J, Vázquez C, Ros E, Buil-Cosiales P, Becerra-Tomas N, Martinez-Lacruz R, Schröder H, Konieczna J, Garcia-de-la-Hera M, Moreno-Rodriguez A, Barón-López J, Pérez-Farinós N, Abete I, Bautista-Castaño I, Casas R, Muñoz-Garach A, Santos-Lozano JM, Trias F, Gallardo-Alfaro L, Ruiz-Canela M, Barragan R, Goday A, Galmés-Panadés AM, González-Botella A, Vaquero-Luna J, Toledo E, Castañer O, Salas-Salvadó J

Abstract

Research examining associations between objectively-measured napping time and type 2 diabetes (T2D) is lacking. This study aimed to evaluate daytime napping in relation to T2D and adiposity measures in elderly individuals from the Mediterranean region. A cross-sectional analysis of baseline data from 2190 elderly participants with overweight/obesity and metabolic syndrome, in the PREDIMED-Plus trial, was carried out. Accelerometer-derived napping was measured. Prevalence ratios (PR) and 95% confidence intervals (CI) for T2D were obtained using multivariable-adjusted Cox regression with constant time. Linear regression models were fitted to examine associations of napping with body mass index (BMI) and waist circumference (WC). Participants napping ?90 min had a higher prevalence of T2D (PR 1.37 (1.06, 1.78)) compared with those napping 5 to <30 min per day. Significant positive associations with BMI and WC were found in those participants napping ?30 min as compared to those napping 5 to <30 min per day. The findings of this study suggest that longer daytime napping is associated with higher T2D prevalence and greater adiposity measures in an elderly Spanish population at high cardiovascular risk.

Published
2019

41. Legume consumption and risk of all-cause, cardiovascular, and cancer mortality in the PREDIMED study

Author

Universitat Rovira i Virgili, Papandreou C; Becerra-Tomás N; Bulló M; Martínez-González MÁ; Corella D; Estruch R; Ros E; Arós F; Schroder H; Fitó M; Serra-Majem L; Lapetra J; Fiol M; Ruiz-Canela M; Sorli JV; Salas-Salvadó J, Universitat Rovira i Virgili, and Papandreou C; Becerra-Tomás N; Bulló M; Martínez-González MÁ; Corella D; Estruch R; Ros E; Arós F; Schroder H; Fitó M; Serra-Majem L; Lapetra J; Fiol M; Ruiz-Canela M; Sorli JV; Salas-Salvadó J

Abstract

Limited prospective studies have examined the association between legumes consumption and mortality, whereas scarce, if at all, previous studies have evaluated such associations taking into consideration specific grain legumes. We aimed to investigate the association between total legumes consumption and grain legumes species (dry beans, chickpeas, lentils, and fresh peas) with all-cause, cardiovascular disease (CVD), cancer and other-cause mortality among elderly Mediterranean individuals at high CVD risk.We prospectively assessed 7216 participants from the PREvención con DIeta MEDiterránea study. Dietary intake was assessed at baseline and yearly during follow-up by using a validated food frequency questionnaire.During a median follow-up of 6.0 years, 425 total deaths, 103 CVD deaths, 169 cancer deaths and 153 due to other-causes deaths occurred. Hazard ratios (HRs) [95% confidence interval (CI)] of CVD mortality were 1.52 (1.02-2.89) (P-trend = 0.034) and 2.23 (1.32-3.78) (P-trend = 0.002) for the 3rd tertile of total legumes and dry beans consumption, respectively, compared with the 1st tertile. When comparing extreme tertiles, higher total legumes and lentils consumption was associated with 49% (HR: 0.51; 95% CI: 0.31-0.84; P-trend = 0.009) and 37% (HR: 0.63; 95% CI: 0.40-0.98; P-trend = 0.049) lower risk of cancer mortality. Similar associations were observed for CVD death in males and for cancer death in males, obese and diabetic participants.These findings support the benefits of legumes consumption for cancer mortality prevention which may be counterbalanced by their higher risk for CVD mortality.The trial is registered at http://www.controlled-trials.com (ISRCTN35739639). Registration date: 5th October 2005.Copyright © 2018 Elsevier Ltd and European Society fo

Published
2019

42. Dietary inflammatory index and all-cause mortality in large cohorts: The SUN and PREDIMED studies

Author

Garcia-Arellano, Ana, primary, Martínez-González, Miguel A., additional, Ramallal, Raul, additional, Salas-Salvadó, Jordi, additional, Hébert, James R., additional, Corella, Dolores, additional, Shivappa, Nitin, additional, Forga, Luis, additional, Schröder, Helmut, additional, Muñoz-Bravo, Carlos, additional, Estruch, Ramón, additional, Fiol, Miquel, additional, Lapetra, José, additional, Serra-Majem, Lluís, additional, Ros, Emilio, additional, Rekondo, Javier, additional, Toledo, Estefanía, additional, Razquin, Cristina, additional, Ruiz-Canela, Miguel, additional, Alonso, A., additional, Barrio Lopez, M.T., additional, Basterra-Gortari, F.J., additional, Benito Corchon, S., additional, Bes-Rastrollo, M., additional, Beunza, J.J., additional, Carlos, S., additional, Cervantes, S., additional, de Irala, J., additional, de la Rosa, P.A., additional, de la Fuente, C., additional, Donat-Vargas, C.L., additional, Donazar, M., additional, Fernandez Montero, A., additional, Gea, A., additional, Goni-Ochandorena, E., additional, Guillen-Grima, F., additional, Lahortiga, F., additional, Llorca, J., additional, Lopez del Burgo, C., additional, Mari-Sanchıs, A., additional, Marti, A., additional, Mendonça, R., additional, Nuñez-Cordoba, J.M., additional, Pimenta, A.M., additional, Rico, A., additional, Ruiz Zambrana, A., additional, Sayon-Orea, C., additional, Toledo-Atucha, J., additional, Vazquez Ruiz, Z., additional, Zazpe Garcıa, I., additional, Sánchez- Tainta, A., additional, Buil-Cosiales, P., additional, Díez-Espino, J., additional, Sanjulian, B., additional, Martínez, J.A., additional, Serrano-Martínez, M., additional, Extremera-Urabayen, J.V., additional, Garcia-Pérez, L., additional, Arroyo-Azpa, C., additional, Barcena, A.F., additional, Oreja-Arrayago, C., additional, Lasanta-Sáez, M.J., additional, Cia-Lecumberri, P., additional, Elcarte-Lopez, T., additional, Artal-Moneva, F., additional, Esparza-López, J.M., additional, Figuerido-Garmendia, E., additional, Tabar-Sarrias, J.A., additional, Fernández- Urzainqui, L., additional, Ariz-Arnedo, M.J., additional, Cabeza-Beunza, J.A., additional, Pascual-Pascual, P., additional, Martínez-Mazo, M.D., additional, Arina-Vergara, E., additional, Macua-Martínez, T., additional, Pascual Pascual, P., additional, Garcés Ducar, M.L., additional, Martí Massó, R., additional, Villanueva Moreno, R., additional, Parra-Osés, A., additional, Serra-Mir, M., additional, Pérez-Heras, A., additional, Viñas, C., additional, Casas, R., additional, Medina-Remon, A., additional, Villanueva, P., additional, Baena, J.M., additional, García, M., additional, Oller, M., additional, Amat, J., additional, Duaso, I., additional, García, Y., additional, Iglesias, C., additional, Simón, C., additional, Quinzavos, L., additional, Parra, L., additional, Liroz, M., additional, Benavent, J., additional, Clos, J., additional, Pla, I., additional, Amorós, M., additional, Bonet, M.T., additional, Martín, M.T., additional, Sánchez, M.S., additional, Altirriba, J., additional, Manzano, E., additional, Altés, A., additional, Cofán, M., additional, Valls-Pedret, C., additional, Sala-Vila, A., additional, Doménech, M., additional, Bulló, M., additional, Basora-Gallisa, J., additional, González, R., additional, Molina, C., additional, Mena, G., additional, Martínez, P., additional, Ibarrola, N., additional, Sorlí, J., additional, García Roselló, J., additional, Martin, F., additional, Tort, N., additional, Isach, A., additional, Babio, N., additional, Salas-Huetos, A., additional, Becerra-Tomás, N., additional, Rosique- Esteban, N., additional, Hernandez, P., additional, Canudas, S., additional, Papandreou, C., additional, Ferreira, C., additional, Cabre, M., additional, Mestres, G., additional, Paris, F., additional, Llauradó, M., additional, Pedret, R., additional, Basells, J., additional, Vizcaino, J., additional, Segarra, R., additional, Giardina, S., additional, Guasch-Ferré, M., additional, Díaz-López, A., additional, Fernández-Ballart, J., additional, Balanza, R., additional, Tello, S., additional, Vila, J., additional, de la Torre, R., additional, Muñoz-Aguayo, D., additional, Elosua, R., additional, Marrugat, J., additional, Schröder, H., additional, Molina, N., additional, Maestre, E., additional, Rovira, A., additional, Castañer, O., additional, Farré, M., additional, Sorli, J., additional, Carrasco, P., additional, Ortega-Azorín, C., additional, Asensio, E.M., additional, Osma, R., additional, Barragán, R., additional, Francés, F., additional, Guillén, M., additional, González, J.I., additional, Sáiz, C., additional, Portolés, O., additional, Giménez, F.J., additional, Coltell, O., additional, Fernández-Carrión, R., additional, Guillem-Sáiz, P., additional, González-Monje, I., additional, Quiles, L., additional, Pascual, V., additional, Riera, C., additional, Pages, M.A., additional, Godoy, D., additional, Carratalá-Calvo, A., additional, Sánchez-Navarro, S., additional, Valero-Barceló, C., additional, Salaverria, I., additional, Hierro, T. del, additional, Algorta, J., additional, Francisco, S., additional, San Vicente, J., additional, Casi, A., additional, Sanz, E., additional, Felipe, I., additional, Rekondo, J., additional, Loma-Osorio, A., additional, Fernandez-Crehuet, J., additional, Garcia-Rodriguez, A., additional, Wärnberg, J., additional, Benitez Pont, R., additional, Bianchi Alba, M., additional, Navajas, R., additional, Gómez-Huelgas, R., additional, Martínez-González, J., additional, Velasco García, V., additional, de Diego Salas, J., additional, Baca Osorio, A., additional, Gil Zarzosa, J., additional, Sánchez Luque, J.J., additional, Vargas López, E., additional, Romaguera, D., additional, García-Valdueza, M., additional, Proenza, A., additional, Prieto, R., additional, Frontera, G., additional, Munuera, S., additional, Vivó, M., additional, Bestard, F., additional, Munar, J.A., additional, Coll, L., additional, Fiol, F., additional, Ginard, M., additional, Jover, A., additional, García, J., additional, Santos-Lozano, J.M., additional, Ortega-Calvo, M., additional, Leal, M., additional, Martínez, E., additional, Mellado, L., additional, Miró-Moriano, L., additional, Domínguez-Espinaco, C., additional, Vaquero- Diaz, S., additional, Iglesias, P., additional, Román, P., additional, Corchado, Y., additional, Lozano-Rodríguez, J.M., additional, Lamuela-Raventós, R., additional, López- Sabater, M.C., additional, Castellote-Bargalló, A.I., additional, Quifer-Rada, P., additional, Tresserra-Rimbau, A., additional, Alvarez-Pérez, J., additional, Díez Benítez, E., additional, Bautista Castaño, I., additional, Maldonado Díaz, I., additional, Sanchez-Villegas, A., additional, Férnandez- Rodríguez, M.J., additional, Sarmiendo de la Fe, F., additional, Simón García, C., additional, Falcón Sanabria, I., additional, Macías Gutiérrez, B., additional, Santana Santana, A.J., additional, de la Cruz, E., additional, Galera, A., additional, Pintó-Salas, X., additional, Trias, F., additional, Sarasa, I., additional, Rodríguez, M.A., additional, Corbella, X., additional, Corbella, E., additional, Goday, A., additional, Muñoz, M.A., additional, Cabezas, C., additional, Vinyoles, E., additional, Rovira, M.A., additional, Garcia, L., additional, Baby, P., additional, Ramos, A., additional, Mengual, L., additional, Roura, P., additional, Yuste, M.C., additional, Guarner, A., additional, Santamaria, M.I., additional, Mata, M., additional, de Juan, C., additional, Brau, A., additional, Fernandez, M., additional, Gutierrez, E., additional, Murillo, C., additional, Garcia, J., additional, Tafalla, M., additional, Bobe, I., additional, Díaz, A., additional, Araque, M., additional, Solis, E., additional, Cervello, T., additional, Montull, I., additional, Tur, J.A., additional, Portillo, M.P., additional, and Sáez, G., additional

Published
2019
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45. P159 - Should patients with active urological cancers receive thromboprophylaxis for Cancer Associated Thrombosis (CAT)?

Author

Tsoukalas, N.G., Christopoulou, A., Timotheadou, E., Koumarianou, A., Athanasiadis, I., Peroukidis, S., Samelis, G., Psyrri, A., Papandreou, C., Kapodistrias, N., Papatsimpas, G., Papakostas, P., Aravantinos, G., Ziras, N., Nikolakopoulos, A., Demiri, S., Andreadis, C., Ardavanis, A., Sgouros, I., Bokas, A., Barbounis, V., Kentepozidis, N., Mavroudis, D., Papakotoulas, P., and Boukovinas, I.

Published
2021
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46. Legume consumption is inversely associated with type 2 diabetes incidence in adults: A prospective assessment from the PREDIMED study

Author

Becerra-Tomás, Nerea, Díaz-López, A., Rosique-Esteban, N., Ros, E., Buil-Cosiales, P., Corella, D., Estruch, R., Fitó, Montserrat, Serra-Majem, L., Arós, F., Lamuela-Raventós, Rosa M., Gueto Rubio, M.V., Loma-Osorio, A., Gómez-Gracia, Enrique, Wärnberg, J., Duaso, I., Rovira, M.A., Benítez Pont, R., Perona, Javier S., Bianchi Alba, M., de la Cruz, E., Basora, J., Brau, A., Salas-Salvadó, J., Bonet, M.T., Gómez-Huelgas, R., Guillén, M., Martínez-González, J., Berrade, N., Molina, C., Casas, Ricard, Sáez, G., Guasch-Ferré, Marta, Iglesias, C., Serra-Mir, M., Velasco García, V., Márquez, F., Montero Romero, Emilio, Vila, J., García-García, M., del Hierro, T., Coltell, O., Jurado-Ruíz, Enrique, Cabré, J.J., Romaguera, D., Valero-Barceló, C., García, M., Costa-Vizcaino, J., Altirriba, J., Prieto, R., García-Valdueza, M., Frontera, G., Fiol, F., Ginard, M., Mestres, G., García, Y., Jover, A., Sorlí, M., Ibarrola-Jurado, Nuria, Molina, N., García, J., Salas-Huetos, A., López-Sabater, M.C., Martínez-Lapiscina, E.H., García Pastor, J.A., Sánchez Luque, J.J., González, J.I., Martín, F., Manzano, E., Fanlo-Maresma, M., Viñas, C., Sáiz, C., Galera, A., Churio-Beraza, B., Trias, F., Bestard, F., Extremera-Urabayen, V., de la Torre, Rafael, Medina-Remón, Alexander, Tort, N., Tello, S., Papandreou, C., Verdú, J.M., Sarasa, I., Muñoz-Aguayo, Daniel, Baby, P., Baena, J.M., Paris, F., Ramos, A., Díaz-Benítez, E.M., Francisco, S., Mengual, L., Ruiz-Canela, M., Roura, P., de Diego Salas, J., Castro Dorado, Antonio, Goñi, E., Fernández-Carrión, R., Fernández-Ballart, J., Yuste, M.C., Aldamiz-Echevarría, M., Alonso-Gómez, A.M., Berjón, J., Sanjulián, B., Montañes, D., Forga, L., Schröder, H., Marrugat, J., Llauradó, M., Giménez, F.J., Gallego, J., Vázquez, Z., García-Layana, A., Moñino, M., Larrauri, A., Vinyoles, E., Rovira, A., Guillem-Saiz, P., Eguaras, S., Simón, C., Oller, M., Salaverria, I., Quinzavos, L., Quifer-Rada, P., Parra, L., de Juan, C., Sarmiento de la Fe, F., Liroz, M., Benavent, J., Castellote-Bargalló, Ana I., Farré, M., Baca Osorio, A., Arroyo-Azpa, C., Altés, A., Clos, J., Cofán, M., Valls-Pedret, C., Sala-Vila, A., Sánchez-Tainta, A., Doménech, M., Portolés, Olga, Algorta, J., Pérez-Cabrera, J., Bulló, M., Gil Zarzosa, J., Babio, N., Corbella, Emili, Maestre, E., Munuera, S., Sanz, E., García-Pérez, L., Pedret, R., Isach, A., Vivó, M., Basells, J., Guarner, A., Vizcaino, J., Martín, M. T., Tresserra-Rimbau, A., Castañer, O., Rekondo, J., Díaz-González, B.V., Ruiz-Gutiérrez, Valentina, Carrasco, P., Segarra, R., Álvarez-Pérez, J., Ortega-Azorín, Carolina, Fiol, Miquel, Asensio, E.M., Martínez, P., Tur, J.A., Osma, R., Castillo Anzalas, J.M., Barragán, R., Portu-Zapirain, J., Alonso-Gómez, A., Corbella, X., Coll, L., González-Monje, I., Francés, F., Quiles, L., Pascual, V., Riera, C., Sosa-Also, R.E., Vargas López, E., Pages, M.A., Casañas-Quintana, L.T., Sánchez-Villegas, A., Pérez-Heras, A., Godoy, D., Cabezas, C., Carratalá-Calvo, A., Pla, I., Sánchez-Navarro, S., Boj, J., Santamaría, M.I., Bautista-Castaño, Inmaculada, Proenza, A., Martí, A., Toledo, E., Mata, M., González, R., SerranoMartínez, M., Sánchez, M.S., Díez-Espino, Javier, Santos-Lozano, J.M., Munar, J.A., Timiraus-Fernández, J., García, L., Villanueva-Tellería, J., García-Arellano, A., Cortés-Ugalde, F., Sagredo-Arce, T., Medina-Ponce, J., Vigata-López, M.D., Elosua, R., García Roselló, J., Arceiz Campo, M.T., Amat, J., Urtasun-Samper, A., Frigola, J., Ruano-Rodríguez, C., Amorós, M., Portillo, María P., Flores-Mateo, Gemma, Belló, M.C., Becerra-Tomás, Nerea, Díaz-López, A., Rosique-Esteban, N., Ros, E., Buil-Cosiales, P., Corella, D., Estruch, R., Fitó, Montserrat, Serra-Majem, L., Arós, F., Lamuela-Raventós, Rosa M., Gueto Rubio, M.V., Loma-Osorio, A., Gómez-Gracia, Enrique, Wärnberg, J., Duaso, I., Rovira, M.A., Benítez Pont, R., Perona, Javier S., Bianchi Alba, M., de la Cruz, E., Basora, J., Brau, A., Salas-Salvadó, J., Bonet, M.T., Gómez-Huelgas, R., Guillén, M., Martínez-González, J., Berrade, N., Molina, C., Casas, Ricard, Sáez, G., Guasch-Ferré, Marta, Iglesias, C., Serra-Mir, M., Velasco García, V., Márquez, F., Montero Romero, Emilio, Vila, J., García-García, M., del Hierro, T., Coltell, O., Jurado-Ruíz, Enrique, Cabré, J.J., Romaguera, D., Valero-Barceló, C., García, M., Costa-Vizcaino, J., Altirriba, J., Prieto, R., García-Valdueza, M., Frontera, G., Fiol, F., Ginard, M., Mestres, G., García, Y., Jover, A., Sorlí, M., Ibarrola-Jurado, Nuria, Molina, N., García, J., Salas-Huetos, A., López-Sabater, M.C., Martínez-Lapiscina, E.H., García Pastor, J.A., Sánchez Luque, J.J., González, J.I., Martín, F., Manzano, E., Fanlo-Maresma, M., Viñas, C., Sáiz, C., Galera, A., Churio-Beraza, B., Trias, F., Bestard, F., Extremera-Urabayen, V., de la Torre, Rafael, Medina-Remón, Alexander, Tort, N., Tello, S., Papandreou, C., Verdú, J.M., Sarasa, I., Muñoz-Aguayo, Daniel, Baby, P., Baena, J.M., Paris, F., Ramos, A., Díaz-Benítez, E.M., Francisco, S., Mengual, L., Ruiz-Canela, M., Roura, P., de Diego Salas, J., Castro Dorado, Antonio, Goñi, E., Fernández-Carrión, R., Fernández-Ballart, J., Yuste, M.C., Aldamiz-Echevarría, M., Alonso-Gómez, A.M., Berjón, J., Sanjulián, B., Montañes, D., Forga, L., Schröder, H., Marrugat, J., Llauradó, M., Giménez, F.J., Gallego, J., Vázquez, Z., García-Layana, A., Moñino, M., Larrauri, A., Vinyoles, E., Rovira, A., Guillem-Saiz, P., Eguaras, S., Simón, C., Oller, M., Salaverria, I., Quinzavos, L., Quifer-Rada, P., Parra, L., de Juan, C., Sarmiento de la Fe, F., Liroz, M., Benavent, J., Castellote-Bargalló, Ana I., Farré, M., Baca Osorio, A., Arroyo-Azpa, C., Altés, A., Clos, J., Cofán, M., Valls-Pedret, C., Sala-Vila, A., Sánchez-Tainta, A., Doménech, M., Portolés, Olga, Algorta, J., Pérez-Cabrera, J., Bulló, M., Gil Zarzosa, J., Babio, N., Corbella, Emili, Maestre, E., Munuera, S., Sanz, E., García-Pérez, L., Pedret, R., Isach, A., Vivó, M., Basells, J., Guarner, A., Vizcaino, J., Martín, M. T., Tresserra-Rimbau, A., Castañer, O., Rekondo, J., Díaz-González, B.V., Ruiz-Gutiérrez, Valentina, Carrasco, P., Segarra, R., Álvarez-Pérez, J., Ortega-Azorín, Carolina, Fiol, Miquel, Asensio, E.M., Martínez, P., Tur, J.A., Osma, R., Castillo Anzalas, J.M., Barragán, R., Portu-Zapirain, J., Alonso-Gómez, A., Corbella, X., Coll, L., González-Monje, I., Francés, F., Quiles, L., Pascual, V., Riera, C., Sosa-Also, R.E., Vargas López, E., Pages, M.A., Casañas-Quintana, L.T., Sánchez-Villegas, A., Pérez-Heras, A., Godoy, D., Cabezas, C., Carratalá-Calvo, A., Pla, I., Sánchez-Navarro, S., Boj, J., Santamaría, M.I., Bautista-Castaño, Inmaculada, Proenza, A., Martí, A., Toledo, E., Mata, M., González, R., SerranoMartínez, M., Sánchez, M.S., Díez-Espino, Javier, Santos-Lozano, J.M., Munar, J.A., Timiraus-Fernández, J., García, L., Villanueva-Tellería, J., García-Arellano, A., Cortés-Ugalde, F., Sagredo-Arce, T., Medina-Ponce, J., Vigata-López, M.D., Elosua, R., García Roselló, J., Arceiz Campo, M.T., Amat, J., Urtasun-Samper, A., Frigola, J., Ruano-Rodríguez, C., Amorós, M., Portillo, María P., Flores-Mateo, Gemma, and Belló, M.C.

Abstract

Background & aims: Legumes, a low-energy, nutrient-dense and low glycemic index food, have shown beneficial effects on glycemic control and adiposity. As such, legumes are widely recommended in diabetic diets, even though there is little evidence that their consumption protects against type 2 diabetes. Therefore the aim of the present study was to examine the associations between consumption of total legumes and specific subtypes, and type 2 diabetes risk. We also investigated the effect of theoretically substituting legumes for other protein- or carbohydrate-rich foods. Methods: Prospective assessment of 3349 participants in the PREvención con DIeta MEDiterránea (PREDIMED) study without type 2 diabetes at baseline. Dietary information was assessed at baseline and yearly during follow-up. We used Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for type-2 diabetes incidence according to quartiles of cumulative average consumption of total legumes, lentils, chickpeas, dry beans and fresh peas. Results: During a median follow-up of 4.3 years, 266 new cases of type 2 diabetes occurred. Individuals in the highest quartile of total legume and lentil consumption had a lower risk of diabetes than those in the lowest quartile (HR: 0.65; 95% CI: 0.43, 0.96; P-trend = 0.04; and HR: 0.67; 95% CI: 0.46–0.98; P-trend = 0.05, respectively). A borderline significant association was also observed for chickpeas consumption (HR 0.68; 95% CI: 0.46, 1.00; P-trend = 0.06). Substitutions of half a serving/day of legumes for similar servings of eggs, bread, rice or baked potato was associated with lower risk of diabetes incidence. Conclusions: A frequent consumption of legumes, particularly lentils, in the context of a Mediterranean diet, may provide benefits on type 2 diabetes prevention in older adults at high cardiovascular risk. Trial registration: The trial is registered at http://www.controlled-trials.com (ISRCTN35739639). Registration dat

Published
2018

47. Association of tryptophan metabolites with incident type 2 diabetes in the PREDIMED trial: A case–cohort study

Author

Universitat Rovira i Virgili, Yu E; Papandreou C; Ruiz-Canela M; Guasch-Ferre M; Clish CB; Dennis C; Liang L; Corella D; Fitó M; Razquin C; Lapetra J; Estruch R; Ros E; Cofán M; Arós F; Toledo E; Serra-Majem L; Sorlí JV; Hu FB; Martinez-Gonzalez MA; Salas-Salvado J, Universitat Rovira i Virgili, and Yu E; Papandreou C; Ruiz-Canela M; Guasch-Ferre M; Clish CB; Dennis C; Liang L; Corella D; Fitó M; Razquin C; Lapetra J; Estruch R; Ros E; Cofán M; Arós F; Toledo E; Serra-Majem L; Sorlí JV; Hu FB; Martinez-Gonzalez MA; Salas-Salvado J

Abstract

© 2018 American Association for Clinical Chemistry. BACKGROUND: Metabolites of the tryptophan– kynurenine pathway (i.e., tryptophan, kynurenine, kynurenic acid, quinolinic acid, 3-hydroxyanthranilic) may be associated with diabetes development. Using a case– cohort design nested in the Prevención con Dieta Mediterránea (PREDIMED) study, we studied the associations of baseline and 1-year changes of these metabolites with incident type 2 diabetes (T2D). METHODS: Plasma metabolite concentrations were quantified via LC-MS for n 641 in a randomly selected subcohort and 251 incident cases diagnosed during 3.8 years of median follow-up. Weighted Cox models adjusted for age, sex, body mass index, and other T2D risk factors were used. RESULTS: Baseline tryptophan was associated with higher risk of incident T2D (hazard ratio 1.29; 95% CI, 1.04 –1.61 per SD). Positive changes in quinolinic acid from baseline to 1 year were associated with a higher risk of T2D (hazard ratio 1.39; 95% CI, 1.09 –1.77 per SD). Baseline tryptophan and kynurenic acid were directly associated with changes in homeostatic model assessment for insulin resistance (HOMA-IR) from baseline to 1 year. Concurrent changes in kynurenine, quinolinic acid, 3-hydroxyanthranilic acid, and kynurenine/tryptophan ratio were associated with baseline-to-1-year changes in HOMA-IR. CONCLUSIONS: Baseline tryptophan and 1-year increases in quinolinic acid were positively associated with incident T2D. Baseline and 1-year changes in tryptophan metabolites predicted changes in HOMA-IR. Tryptophan levels may initially increase and then deplete as diabetes progresses in severity.

Published
2018

48. Plasma branched chain/aromatic amino acids, enriched Mediterranean diet and risk of type 2 diabetes: case-cohort study within the PREDIMED Trial

Author

Universitat Rovira i Virgili, Ruiz-Canela M; Guasch-Ferré M; Toledo E; Clish C; Razquin C; Liang L; Wang D; Corella D; Estruch R; Hernáez Á; Yu E; Gómez-Gracia E; Zheng Y; Arós F; Romaguera D; Dennis C; Ros E; Lapetra J; Serra-Majem L; Papandreou C; Portoles O; Fitó M; Salas-Salvadó J; Hu F; Martínez-González M, Universitat Rovira i Virgili, and Ruiz-Canela M; Guasch-Ferré M; Toledo E; Clish C; Razquin C; Liang L; Wang D; Corella D; Estruch R; Hernáez Á; Yu E; Gómez-Gracia E; Zheng Y; Arós F; Romaguera D; Dennis C; Ros E; Lapetra J; Serra-Majem L; Papandreou C; Portoles O; Fitó M; Salas-Salvadó J; Hu F; Martínez-González M

Abstract

Branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) are associated with type 2 diabetes. However, repeated measurements of BCAA/AAA and their interactions with dietary interventions have not been evaluated. We investigated the associations between baseline and changes at 1 year in BCAA/AAA with type 2 diabetes in the context of a Mediterranean diet (MedDiet) trial.We included 251 participants with incident type 2 diabetes and a random sample of 694 participants (641 participants without type 2 diabetes and 53 overlapping cases) in a case-cohort study nested within the PREvención con DIeta MEDiterránea (PREDIMED) trial. Participants were randomised to a MedDiet+extra-virgin olive oil (n?=?273), a MedDiet+nuts (n?=?324) or a control diet (n?=?295). We used LC-MS/MS to measure plasma levels of amino acids. Type 2 diabetes was a pre-specified secondary outcome of the PREDIMED trial.Elevated plasma levels of individual BCAAs/AAAs were associated with higher type 2 diabetes risk after a median follow-up of 3.8 years: multivariable HR for the highest vs lowest quartile ranged from 1.32 for phenylalanine ([95% CI 0.90, 1.92], p for trend?=?0.015) to 3.29 for leucine ([95% CI 2.03, 5.34], p for trend<0.001). Increases in BCAA score at 1 year were associated with higher type 2 diabetes risk in the control group with HR per SD?=?1.61 (95% CI 1.02, 2.54), but not in the MedDiet groups (p for interaction <0.001). The MedDiet+extra-virgin olive oil significantly reduced BCAA levels after 1 year of intervention (p?= 0.005 vs the control group).Our results support that higher baseline BCAAs and their increases at 1 year were associated with higher type 2 diabetes risk. A Mediterranean diet rich in extra-virgin olive oil significantly reduced the levels of BCAA and attenu

Published
2018

49. Plasma Lipidomic Profiling and Risk of Type 2 Diabetes in the PREDIMED Trial

Author

Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Razquin C; Toledo E; Clish CB; Ruiz-Canela M; Dennis C; Corella D; Papandreou C; Ros E; Estruch R; Guasch-Ferré M; Gómez-Gracia E; Fitó M; Yu E; Lapetra J; Wang D; Romaguera D; Liang L; Alonso-Gómez A; Deik A; Bullo M; Serra-Majem L; Salas-Salvadó J; Hu FB; Martínez-González MA, Bioquímica i Biotecnologia, Universitat Rovira i Virgili, and Razquin C; Toledo E; Clish CB; Ruiz-Canela M; Dennis C; Corella D; Papandreou C; Ros E; Estruch R; Guasch-Ferré M; Gómez-Gracia E; Fitó M; Yu E; Lapetra J; Wang D; Romaguera D; Liang L; Alonso-Gómez A; Deik A; Bullo M; Serra-Majem L; Salas-Salvadó J; Hu FB; Martínez-González MA

Abstract

© 2018 by the American Diabetes Association. OBJECTIVE: Specific lipid molecular changes leading to type 2 diabetes (T2D) are largely unknown. We assessed lipidome factors associated with future occurrence of T2D in a population at high cardiovascular risk. RESEARCH DESIGN AND METHODS: We conducted a case-cohort study nested within the PREDIMED trial, with 250 incident T2D cases diagnosed during 3.8 years of median follow-up, and a random sample of 692 participants (639 noncases and 53 overlapping cases) without T2D at baseline. We repeatedly measured 207 plasma known lipid metabolites at baseline and after 1 year of follow-up. We built combined factors of lipid species using principal component analysis and assessed the association between these lipid factors (or their 1-year changes) and T2D incidence. RESULTS: Baseline lysophosphatidylcholines and lysophosphatidylethanolamines (lysophospholipids [LPs]), phosphatidylcholine-plasmalogens (PC-PLs), sphingomyelins (SMs), and cholesterol esters (CEs) were inversely associated with risk of T2D (multivariable-adjusted P for linear trend ≤0.001 for all). Baseline triacylglycerols (TAGs), diacylglycerols (DAGs), and phosphatidylethanolamines (PEs) were positively associated with T2D risk (multivariable-adjusted P for linear trend <0.001 for all). One-year changes in these lipids showed associations in similar directions but were not significant after adjustment for baseline levels. TAGs with odd-chain fatty acids showed inverse associations with T2D after adjusting for total TAGs. CONCLUSIONS: Two plasma lipid profiles made up of different lipid classes were found to be associated with T2D in participants at high cardiovascular risk. A profile including LPs, PC-PLs, SMs, and CEs was associated with lower T2D risk. Another pro

Published
2018

50. Cross-sectional associations of objectively-measured sleep characteristics with obesity and type 2 diabetes in the PREDIMED-Plus trial.

Author

Universitat Rovira i Virgili, Rosique-Esteban N, Papandreou C, Romaguera D, Warnberg J, Corella D, Martínez-González MÁ, Díaz-López A, Estruch R, Vioque J, Arós F, Garcia-Rios A, Bueno-Cavanillas A, Vidal J, Serra-Majem L, Sibai AA, Tinahones FJ, Martínez JA, Ordovás JM, Tur JA, Ellacuría MT, Sanllorente A, Pintó X, Buil-Cosiales P, Fernández-Carrion R, Castañer O, Bulló M, Ruiz-Canela M, Garcia-de la Hera M, Pérez-Farinós N, Barón-López FJ, Colom A, Abete I, Ros E, Salas-Salvadó J, Universitat Rovira i Virgili, and Rosique-Esteban N, Papandreou C, Romaguera D, Warnberg J, Corella D, Martínez-González MÁ, Díaz-López A, Estruch R, Vioque J, Arós F, Garcia-Rios A, Bueno-Cavanillas A, Vidal J, Serra-Majem L, Sibai AA, Tinahones FJ, Martínez JA, Ordovás JM, Tur JA, Ellacuría MT, Sanllorente A, Pintó X, Buil-Cosiales P, Fernández-Carrion R, Castañer O, Bulló M, Ruiz-Canela M, Garcia-de la Hera M, Pérez-Farinós N, Barón-López FJ, Colom A, Abete I, Ros E, Salas-Salvadó J

Abstract

To examine independent and combined associations of sleep duration and sleep variability with body composition, obesity and type 2 diabetes (T2D) in elders at high cardiovascular risk.Cross-sectional analysis of 1986 community-dwelling elders with overweight/obesity and metabolic syndrome from PREDIMED-Plus trial. Associations of accelerometry-derived sleep duration and sleep variability with body mass index (BMI), waist circumference (WC) and body composition were assessed fitting multivariable-adjusted linear regression models. Prevalence ratios (PR) and 95% confidence intervals (CI) for obesity and T2D were obtained using multivariable-adjusted Cox regression with constant time. "Bad sleepers" (age-specific non-recommended sleep duration plus sleep variability above the median) and "good sleepers" (age-specific recommended sleep duration plus sleep variability below the median) were characterized by combining sleep duration and sleep variability, and their associations with these outcomes were examined.One hour/night increment in sleep duration was inversely associated with BMI (? -0.38 kg/m 2 [95% CI -0.54, -0.23]), WC (? -0.86 cm [95% CI -1.25, -0.47]), obesity (PR 0.96 [95% CI 0.93, 0.98]), T2D (PR 0.93 [95% CI 0.88, 0.98]) and other DXA-derived adiposity-related measurements (android fat and trunk fat, all p < .05). Each 1-hour increment in sleep variability was positively associated with T2D (PR 1.14 [95% CI 1.01, 1.28]). Compared with "good sleepers," "bad sleepers" were positively associated with obesity (PR 1.12 [95% CI 1.01, 1.24]) and T2D (PR 1.62 [95% CI 1.28, 2.06]).This study revealed cross-sectional associations of sleep duration with adiposity parameters and obesity. Sleep duration and sleep variability were associated with T2D. Considering simultaneou

Published
2018

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