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1. An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Author: Blein, S, Bardel, C, Danjean, V, McGuffog, L, Healey, S, Barrowdale, D, Lee, A, Dennis, J, Kuchenbaecker, KB, Soucy, P, Terry, MB, Chung, WK, Goldgar, DE, Buys, SS, Janavicius, R, Tihomirova, L, Tung, N, Dorfling, CM, van Rensburg, EJ, Neuhausen, SL, Ding, YC, Gerdes, AM, Ejlertsen, B, Nielsen, FC, Hansen, TVO, Osorio, A, Benitez, J, Conejero, RA, Segota, E, Weitzel, JN, Thelander, M, Peterlongo, P, Radice, P, Pensotti, V, Dolcetti, R, Bonanni, B, Peissel, B, Zaffaroni, D, Scuvera, G, Manoukian, S, Varesco, L, Capone, GL, Papi, L, Ottini, L, Yannoukakos, D, Konstantopoulou, I, Garber, J, Hamann, U, Donaldson, A, Brady, A, Brewer, C, Foo, C, Evans, DG, Frost, D, Eccles, D, Douglas, F, Cook, J, Adlard, J, Barwell, J, Walker, L, Izatt, L, Side, LE, Kennedy, MJ, Tischkowitz, M, Rogers, MT, Porteous, ME, Morrison, PJ, Platte, R, Eeles, R, Davidson, R, Hodgson, S, Cole, T, Godwin, AK, Isaacs, C, Claes, K, De Leeneer, K, Meindl, A, Gehrig, A, Wappenschmidt, B, Sutter, C, Engel, C, Niederacher, D, Steinemann, D, Plendl, H, Kast, K, Rhiem, K, Ditsch, N, Arnold, N, Varon-Mateeva, R, Schmutzler, RK, Preisler-Adams, S, Markov, NB, Wang-Gohrke, S, de Pauw, A, Lefol, C, Lasset, C, Leroux, D, Rouleau, E, Damiola, F, and Dreyfus, H
Subjects: Oncology & Carcinogenesis, Oncology and Carcinogenesis
Abstract: Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.
Published: 2015

2. Performance of Prognostic Risk Scores in Chronic Heart Failure Patients Enrolled in the European Society of Cardiology Heart Failure Long-Term Registry

Author: Crespo-Leiro, M., Anker, S., Mebazaa, A., Coats, A., Filippatos, G., Ferrari, R., Maggioni, A.P., Piepoli, M.F., Amir, O., Chioncel, O., Dahlström, U., Delgado Jimenez, J.F., Drozdz, J., Erglis, A., Fazlibegovic, E., Fonseca, C., Fruhwald, F., Gatzov, P., Goncalvesova, E., Hassanein, M., Hradec, J., Kavoliuniene, A., Lainscak, M., Logeart, D., Merkely, B., Metra, M., Otljanska, M., Seferovic, P.M., Srbinovska Kostovska, E., Temizhan, A., Tousoulis, D., Ferreira, T., Andarala, M., Fiorucci, E., Folkesson Lefrancq, E., Glémot, M., Gracia, G., Konte, M., Laroche, C., McNeill, P.A., Missiamenou, V., Taylor, C., Auer, J., Ablasser, K., Dolze, T., Brandner, K., Gstrein, S., Poelzl, G., Moertl, D., Reiter, S., Podczeck-Schweighofer, A., Muslibegovic, A., Vasilj, M., Cesko, M., Zelenika, D., Palic, B., Pravdic, D., Cuk, D., Vitlianova, K., Katova, T., Velikov, T., Kurteva, T., Kamenova, D., Antova, M., Sirakova, V., Krejci, J., Mikolaskova, M., Spinar, J., Krupicka, J., Malek, F., Hegarova, M., Lazarova, M., Monhart, Z., Sobhy, M., El Messiry, F., El Shazly, A.H., Elrakshy, Y., Youssef, A., Moneim, A.A., Noamany, M., Reda, A., Abdel Dayem, T.K., Farag, N., Ibrahim Halawa, S., Abdel Hamid, M., Said, K., Saleh, A., Ebeid, H., Hanna, R., Aziz, R., Louis, O., Enen, M.A., Ibrahim, B.S., Nasr, G., Elbahry, A., Sobhy, H., Ashmawy, M., Gouda, M., Aboleineen, W., Bernard, Y., Luporsi, P., Meneveau, N., Pillot, M., Morel, M., Seronde, M.-F., Schiele, F., Briand, F., Delahaye, F., Damy, T., Eicher, J.-C., de Groote, P., Fertin, M., Lamblin, N., Isnard, R., Lefol, C., Thevenin, S., Hagege, A., Jondeau, G., Le Marcis, V., Ly, J.-F., Coisne, D., Lequeux, B., Le Moal, V., Mascle, S., Lotton, P., Behar, N., Donal, E., Thebault, C., Ridard, C., Reynaud, A., Basquin, A., Bauer, F., Codjia, R., Galinier, M., Tourikis, P., Stavroula, M., Stefanadis, C., Chrysohoou, C., Kotrogiannis, I., Matzaraki, V., Dimitroula, T., Karavidas, A., Tsitsinakis, G., Kapelios, C., Nanas, J., Kampouri, H., Nana, E., Kaldara, E., Eugenidou, A., Vardas, P., Saloustros, I., Patrianakos, A., Tsaknakis, T., Evangelou, S., Nikoloulis, N., Tziourganou, H., Tsaroucha, A., Papadopoulou, A., Douras, A., Polgar, L., Kosztin, A., Nyolczas, N., Csaba Nagy, A., Halmosi, R., Elber, J., Alony, I., Shotan, A., Vazan Fuhrmann, A., Romano, S., Marcon, S., Penco, M., Di Mauro, M., Lemme, E., Carubelli, V., Rovetta, R., Bulgari, M., Quinzani, F., Lombardi, C., Bosi, S., Schiavina, G., Squeri, A., Barbieri, A., Di Tano, G., Pirelli, S., Fucili, A., Passero, T., Musio, S., Di Biase, M., Correale, M., Salvemini, G., Brognoli, S., Zanelli, E., Giordano, A., Agostoni, P., Italiano, G., Salvioni, E., Copelli, S., Modena, M.G., Reggianini, L., Valenti, C., Olaru, A., Bandino, S., Deidda, M., Mercuro, G., Cadeddu Dessalvi, C., Marino, P.N., Di Ruocco, M.V., Sartori, C., Piccinino, C., Parrinello, G., Licata, G., Torres, D., Giambanco, S., Busalacchi, S., Arrotti, S., Novo, S., Inciardi, R.M., Pieri, P., Chirco, P.R., Ausilia Galifi, M., Teresi, G., Buccheri, D., Minacapelli, A., Veniani, M., Frisinghelli, A., Priori, S.G., Cattaneo, S., Opasich, C., Gualco, A., Pagliaro, M., Mancone, M., Fedele, F., Cinque, A., Vellini, M., Scarfo, I., Romeo, F., Ferraiuolo, F., Sergi, D., Anselmi, M., Melandri, F., Leci, E., Iori, E., Bovolo, V., Pidello, S., Frea, S., Bergerone, S., Botta, M., Canavosio, F.G., Gaita, F., Merlo, M., Cinquetti, M., Sinagra, G., Ramani, F., Fabris, E., Stolfo, D., Artico, J., Miani, D., Fresco, C., Daneluzzi, C., Proclemer, A., Cicoira, M., Zanolla, L., Marchese, G., Torelli, F., Vassanelli, C., Voronina, N., Tamakauskas, V., Smalinskas, V., Karaliute, R., Petraskiene, I., Kazakauskaite, E., Rumbinaite, E., Vysniauskas, V., Brazyte-Ramanauskiene, R., Petraskiene, D., Stankala, S., Switala, P., Juszczyk, Z., Sinkiewicz, W., Gilewski, W., Pietrzak, J., Orzel, T., Kasztelowicz, P., Kardaszewicz, P., Lazorko-Piega, M., Gabryel, J., Mosakowska, K., Bellwon, J., Rynkiewicz, A., Raczak, G., Lewicka, E., Dabrowska-Kugacka, A., Bartkowiak, R., Sosnowska-Pasiarska, B., Wozakowska-Kaplon, B., Krzeminski, A., Zabojszcz, M., Mirek-Bryniarska, E., Grzegorzko, A., Bury, K., Nessler, J., Zalewski, J., Furman, A., Broncel, M., Poliwczak, A., Bala, A., Zycinski, P., Rudzinska, M., Jankowski, L., Kasprzak, J.D., Michalak, L., Wojtczak Soska, K., Huziuk, I., Retwinski, A., Flis, P., Weglarz, J., Bodys, A., Grajek, S., Kaluzna-Oleksy, M., Straburzynska-Migaj, E., Dankowski, R., Szymanowska, K., Grabia, J., Szyszka, A., Nowicka, A., Samcik, M., Wolniewicz, L., Baczynska, K., Komorowska, K., Poprawa, I., Komorowska, E., Sajnaga, D., Zolbach, A., Dudzik-Plocica, A., Abdulkarim, A.-F., Lauko-Rachocka, A., Kaminski, L., Kostka, A., Cichy, A., Ruszkowski, P., Splawski, M., Fitas, G., Szymczyk, A., Serwicka, A., Fiega, A., Zysko, D., Krysiak, W., Szabowski, S., Skorek, E., Pruszczyk, P., Bienias, P., Ciurzynski, M., Welnicki, M., Mamcarz, A., Folga, A., Zielinski, T., Rywik, T., Leszek, P., Sobieszczanska-Malek, M., Piotrowska, M., Kozar-Kaminska, K., Komuda, K., Wisniewska, J., Tarnowska, A., Balsam, P., Marchel, M., Opolski, G., Kaplon-Cieslicka, A., Gil, R.J., Mozenska, O., Byczkowska, K., Gil, K., Pawlak, A., Michalek, A., Krzesinski, P., Piotrowicz, K., Uzieblo-Zyczkowska, B., Stanczyk, A., Skrobowski, A., Ponikowski, P., Jankowska, E., Rozentryt, P., Polonski, L., Gadula-Gacek, E., Nowalany-Kozielska, E., Kuczaj, A., Kalarus, Z., Szulik, M., Przybylska, K., Klys, J., Prokop-Lewicka, G., Kleinrok, A., Tavares Aguiar, C., Ventosa, A., Pereira, S., Faria, R., Chin, J., De Jesus, I., Santos, R., Silva, P., Moreno, N., Queirós, C., Lourenço, C., Pereira, A., Castro, A., Andrade, A., Oliveira Guimaraes, T., Martins, S., Placido, R., Lima, G., Brito, D., Francisco, A.R., Cardiga, R., Proenca, M., Araujo, I., Marques, F., Moura, B., Leite, S., Campelo, M., Silva-Cardoso, J., Rodrigues, J., Rangel, I., Martins, E., Sofia Correia, A., Peres, M., Marta, L., Ferreira da Silva, G., Severino, D., Durao, D., Leao, S., Magalhaes, P., Moreira, I., Filipa Cordeiro, A., Ferreira, C., Araujo, C., Ferreira, A., Baptista, A., Radoi, M., Bicescu, G., Vinereanu, D., Sinescu, C.-J., Macarie, C., Popescu, R., Daha, I., Dan, G.-A., Stanescu, C., Dan, A., Craiu, E., Nechita, E., Aursulesei, V., Christodorescu, R., Otasevic, P., Simeunovic, D., Ristic, A.D., Celic, V., Pavlovic-Kleut, M., Suzic Lazic, J., Stojcevski, B., Pencic, B., Stevanovic, A., Andric, A., Iric-Cupic, V., Jovic, M., Davidovic, G., Milanov, S., Mitic, V., Atanaskovic, V., Antic, S., Pavlovic, M., Stanojevic, D., Stoickov, V., Ilic, S., Deljanin Ilic, M., Petrovic, D., Stojsic, S., Kecojevic, S., Dodic, S., Cemerlic Adic, N., Cankovic, M., Stojiljkovic, J., Mihajlovic, B., Radin, A., Radovanovic, S., Krotin, M., Klabnik, A., Pernicky, M., Murin, J., Kovar, F., Kmec, J., Semjanova, H., Strasek, M., Savnik Iskra, M., Ravnikar, T., Cernic Suligoj, N., Komel, J., Fras, Z., Jug, B., Glavic, T., Losic, R., Bombek, M., Krajnc, I., Krunic, B., Horvat, S., Kovac, D., Rajtman, D., Cencic, V., Letonja, M., Winkler, R., Valentincic, M., Melihen-Bartolic, C., Bartolic, A., Pusnik Vrckovnik, M., Kladnik, M., Slemenik Pusnik, C., Marolt, A., Klen, J., Drnovsek, B., Leskovar, B., Fernandez Anguita, M.J., Gallego Page, J.C., Salmeron Martinez, F.M., Andres, J., Genis, A.B., Mirabet, S., Mendez, A., Garcia-Cosio, L., Roig, E., Leon, V., Gonzalez-Costello, J., Muntane, G., Garay, A., Alcade-Martinez, V., Lopez Fernandez, S., Rivera-Lopez, R., Puga-Martinez, M., Fernandez-Alvarez, M., Serrano-Martinez, J.L., Grille-Cancela, Z., Marzoa-Rivas, R., Blanco-Canosa, P., Paniagua-Martin, M.J., Barge-Caballero, E., Laynez Cerdena, I., Famara Hernandez Baldomero, I., Lara Padron, A., Ofelia Rosillo, S., Dalmau Gonzalez-Gallarza, R., Salvador Montanes, O., Iniesta Manjavacas, A.M., Castro Conde, A., Araujo, A., Soria, T., Garcia-Pavia, P., Gomez-Bueno, M., Cobo-Marcos, M., Alonso-Pulpon, L., Segovia Cubero, J., Sayago, I., Gonzalez-Segovia, A., Briceno, A., Escribano Subias, P., Vicente Hernandez, M., Ruiz Cano, M.J., Gomez Sanchez, M.A., Barrios Garrido-Lestache, E., Garcia Pinilla, J.M., Garcia de la Villa, B., Sahuquillo, A., Bravo Marques, R., Torres Calvo, F., Perez-Martinez, M.T., Gracia-Rodenas, M.R., Garrido-Bravo, I.P., Pastor-Perez, F., Pascual-Figal, D.A., Diaz Molina, B., Orus, J., Epelde Gonzalo, F., Bertomeu, V., Valero, R., Martinez-Abellan, R., Quiles, J., Rodrigez-Ortega, J.A., Mateo, I., ElAmrani, A., Fernandez-Vivancos, C., Bierge Valero, D., Almenar-Bonet, L., Sanchez-Lazaro, I.J., Marques-Sule, E., Facila-Rubio, L., Perez-Silvestre, J., Garcia-Gonzalez, P., Ridocci-Soriano, F., Garcia-Escriva, D., Pellicer-Cabo, A., de la Fuente Galan, L., Lopez Diaz, J., Recio Platero, A., Arias, J.C., Blasco-Peiro, T., Sanz Julve, M., Sanchez-Insa, E., Aured-Guallar, C., Portoles-Ocampo, A., Melin, M., Hägglund, E., Stenberg, A., Lindahl, I.-M., Asserlund, B., Olsson, L., Afzelius, M., Karlström, P., Tengvall, L., Wiklund, P.-A., Olsson, B., Kalayci, S., Cavusoglu, Y., Gencer, E., Yilmaz, M.B., Gunes, H., Canepa, Marco, Fonseca, Candida, Chioncel, Ovidiu, Laroche, Cécile, Crespo-Leiro, Maria G., Coats, Andrew J.S., Mebazaa, Alexandre, Piepoli, Massimo F., Tavazzi, Luigi, and Maggioni, Aldo P.
Published: 2018
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3. Breast and ovarian cancer predisposition due to de novo BRCA1 and BRCA2 mutations

Author: Golmard, L, Delnatte, C, Laugé, A, Moncoutier, V, Lefol, C, Abidallah, K, Tenreiro, H, Copigny, F, Giraudeau, M, Guy, C, Barbaroux, C, Amorim, G, Briaux, A, Guibert, V, Tarabeux, J, Caputo, S, Collet, A, Gesta, P, Ingster, O, Stern, M-H, Rouleau, E, de Pauw, A, Gauthier-Villars, M, Buecher, B, Bézieau, S, Stoppa-Lyonnet, D, and Houdayer, C
Published: 2016
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4. Sex‐ and age‐related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long‐Term Registry

Author: Lainscak, M., Milinkovic, I., Polovina, M., Crespo-Leiro, M. G., Lund, L. H., Anker, S. D., Laroche, C., Ferrari, R., Coats, A. J. S., Mcdonagh, T., Filippatos, G., Maggioni, A. P., Piepoli, M. F., Rosano, G. M. C., Ruschitzka, F., Simic, D., Asanin, M., Eicher, J. -C., Yilmaz, M. B., Seferovic, P. M., Gale, C. P., Chair, G. B., Branko Beleslin, R. S., Andrzej Budaj, P. L., Ovidiu Chioncel, R. O., Nikolaos Dagres, D. E., Nicolas Danchin, F. R., David Erlinge, S. E., Jonathan Emberson, G. B., Michael Glikson, I. L., Alastair Gray, G. B., Meral Kayikcioglu, T. R., Aldo Maggioni, I. T., Klaudia Vivien Nagy, H. U., Aleksandr Nedoshivin, R. U., Anna-Sonia Petronio, I. T., Jolien Roos-Hesselink, N. L., Lars Wallentin, S. E., Uwe Zeymer, D. E., Crespo-Leiro, M., Anker, S., Mebazaa, A., Coats, A., A. Goda A. L., M. Diez A. R., A. Fernandez A. R., F. Fruhwald A. T., Fazlibegovic, E., P. Gatzov B. G., A. Kurlianskaya B. Y., R. Hullin C. H., T. Christodoulides C. Y., J. Hradec C. Z., O. Wendelboe Nielsen D. K., R. Nedjar D. Z., T. Uuetoa E. E., M. Hassanein E. G., J. F. Delgado Jimenez E. S., P. Harjola F. I., V, D. Logeart F. R., V. Chumburidze G. E., D. Tousoulis G. R., D. Milicic H. R., B. Merkely H. U., O'Donoghue IE, E., O. Amir I. L., A. Shotan I. L., D. Shafie I. R., M. Metra I. T., A. Matsumori J. P., E. Mirrakhimov K. G., A. Kavoliuniene L. T., A. Erglis L. V., Vataman, E., M. Otljanska M. K., E. Srbinovska Kostovska M. K., D. Cassar DeMarco M. T., J. Drozdz P. L., Fonseca, C., O. Chioncel R. O., M. Dekleva R. S., E. Shkolnik R. U., U. Dahlstrom S. E., M. Lainscak S. I., E. Goncalvesova S. K., A. Temizhan T. R., V. Estrago U. Y., G. Bajraktari X. K., Auer, J., Ablasser, K., Fruhwald, F., Dolze, T., Brandner, K., Gstrein, S., Poelzl, G., Moertl, D., Reiter, S., Podczeck-Schweighofer, A., Muslibegovic, A., Vasilj, M., Cesko, M., Zelenika, D., Palic, B., Pravdic, D., Cuk, D., Vitlianova, K., Katova, T., Velikov, T., Kurteva, T., Gatzov, P., Kamenova, D., Antova, M., Sirakova, V., Krejci, J., Mikolaskova, M., Spinar, J., Krupicka, J., Malek, F., Hegarova, M., Lazarova, M., Monhart, Z., Hassanein, M., Sobhy, M., El Messiry, F., El Shazly, A. H., Elrakshy, Y., Youssef, A., Moneim, A. A., Noamany, M., Reda, A., Dayem, T. K. A., Farag, N., Halawa, S. I., Hamid, M. A., Said, K., Saleh, A., Ebeid, H., Hanna, R., Aziz, R., Louis, O., Enen, M. A., Ibrahim, B. S., Nasr, G., Elbahry, A., Sobhy, H., Ashmawy, M., Gouda, M., Aboleineen, W., Bernard, Y., Luporsi, P., Meneveau, N., Pillot, M., Morel, M., Seronde, M. -F., Schiele, F., Briand, F., Delahaye, F., Damy, T., de Groote, P., Fertin, M., Lamblin, N., Isnard, R., Lefol, C., Thevenin, S., Hagege, A., Jondeau, G., Logeart, D., Le Marcis, V., J. -F., Ly, Coisne, D., Lequeux, B., Le Moal, V., Mascle, S., Lotton, P., Behar, N., Donal, E., Thebault, C., Ridard, C., Reynaud, A., Basquin, A., Bauer, F., Codjia, R., Galinier, M., Tourikis, P., Stavroula, M., Tousoulis, D., Stefanadis, C., Chrysohoou, C., Kotrogiannis, I., Matzaraki, V., Dimitroula, T., Karavidas, A., Tsitsinakis, G., Kapelios, C., Nanas, J., Kampouri, H., Nana, E., Kaldara, E., Eugenidou, A., Vardas, P., Saloustros, I., Patrianakos, A., Tsaknakis, T., Evangelou, S., Nikoloulis, N., Tziourganou, H., Tsaroucha, A., Papadopoulou, A., Douras, A., Polgar, L., Merkely, B., Kosztin, A., Nyolczas, N., Nagy, A. C., Halmosi, R., Elber, J., Alony, I., Shotan, A., Fuhrmann, A. V., Amir, O., Romano, S., Marcon, S., Penco, M., Di Mauro, M., Lemme, E., Carubelli, V., Rovetta, R., Metra, M., Bulgari, M., Quinzani, F., Lombardi, C., Bosi, S., Schiavina, G., Squeri, A., Barbieri, A., Di Tano, G., Pirelli, S., Fucili, A., Passero, T., Musio, S., Di Biase, M., Correale, M., Salvemini, G., Brognoli, S., Zanelli, E., Giordano, A., Agostoni, P., Italiano, G., Salvioni, E., Copelli, S., Modena, M. G., Reggianini, L., Valenti, C., Olaru, A., Bandino, S., Deidda, M., Mercuro, G., Dessalvi, C. C., Marino, P. N., Di Ruocco, M. V., Sartori, C., Piccinino, C., Parrinello, G., Licata, G., Torres, D., Giambanco, S., Busalacchi, S., Arrotti, S., Novo, S., Inciardi, R. M., Pieri, P., Chirco, P. R., Galifi, M. A., Teresi, G., Buccheri, D., Minacapelli, A., Veniani, M., Frisinghelli, A., Priori, S. G., Cattaneo, S., Opasich, C., Gualco, A., Pagliaro, M., Mancone, M., Fedele, F., Cinque, A., Vellini, M., Scarfo, I., Romeo, F., Ferraiuolo, F., Sergi, D., Anselmi, M., Melandri, F., Leci, E., Iori, E., Bovolo, V., Pidello, S., Frea, S., Bergerone, S., Botta, M., Canavosio, F. G., Gaita, F., Merlo, M., Cinquetti, M., Sinagra, G., Ramani, F., Fabris, E., Stolfo, D., Artico, J., Miani, D., Fresco, C., Daneluzzi, C., Proclemer, A., Cicoira, M., Zanolla, L., Marchese, G., Torelli, F., Vassanelli, C., Voronina, N., Erglis, A., Tamakauskas, V., Smalinskas, V., Karaliute, R., Petraskiene, I., Kazakauskaite, E., Rumbinaite, E., Kavoliuniene, A., Vysniauskas, V., Brazyte-Ramanauskiene, R., Petraskiene, D., Stankala, S., Switala, P., Juszczyk, Z., Sinkiewicz, W., Gilewski, W., Pietrzak, J., Orzel, T., Kasztelowicz, P., Kardaszewicz, P., Lazorko-Piega, M., Gabryel, J., Mosakowska, K., Bellwon, J., Rynkiewicz, A., Raczak, G., Lewicka, E., Dabrowska-Kugacka, A., Bartkowiak, R., Sosnowska-Pasiarska, B., Wozakowska-Kaplon, B., Krzeminski, A., Zabojszcz, M., Mirek-Bryniarska, E., Grzegorzko, A., Bury, K., Nessler, J., Zalewski, J., Furman, A., Broncel, M., Poliwczak, A., Bala, A., Zycinski, P., Rudzinska, M., Jankowski, L., Kasprzak, J. D., Michalak, L., Soska, K. W., Drozdz, J., Huziuk, I., Retwinski, A., Flis, P., Weglarz, J., Bodys, A., Grajek, S., Kaluzna-Oleksy, M., Straburzynska-Migaj, E., Dankowski, R., Szymanowska, K., Grabia, J., Szyszka, A., Nowicka, A., Samcik, M., Wolniewicz, L., Baczynska, K., Komorowska, K., Poprawa, I., Komorowska, E., Sajnaga, D., Zolbach, A., Dudzik-Plocica, A., Abdulkarim, A. -F., Lauko-Rachocka, A., Kaminski, L., Kostka, A., Cichy, A., Ruszkowski, P., Splawski, M., Fitas, G., Szymczyk, A., Serwicka, A., Fiega, A., Zysko, D., Krysiak, W., Szabowski, S., Skorek, E., Pruszczyk, P., Bienias, P., Ciurzynski, M., Welnicki, M., Mamcarz, A., Folga, A., Zielinski, T., Rywik, T., Leszek, P., Sobieszczanska-Malek, M., Piotrowska, M., Kozar-Kaminska, K., Komuda, K., Wisniewska, J., Tarnowska, A., Balsam, P., Marchel, M., Opolski, G., Kaplon-Cieslicka, A., Gil, R. J., Mozenska, O., Byczkowska, K., Gil, K., Pawlak, A., Michalek, A., Krzesinski, P., Piotrowicz, K., Uzieblo-Zyczkowska, B., Stanczyk, A., Skrobowski, A., Ponikowski, P., Jankowska, E., Rozentryt, P., Polonski, L., Gadula-Gacek, E., Nowalany-Kozielska, E., Kuczaj, A., Kalarus, Z., Szulik, M., Przybylska, K., Klys, J., Prokop-Lewicka, G., Kleinrok, A., Aguiar, C. T., Ventosa, A., Pereira, S., Faria, R., Chin, J., De Jesus, I., Santos, R., Silva, P., Moreno, N., Queiros, C., Lourenco, C., Pereira, A., Castro, A., Andrade, A., Guimaraes, T. O., Martins, S., Placido, R., Lima, G., Brito, D., Francisco, A. R., Cardiga, R., Proenca, M., Araujo, I., Marques, F., Moura, B., Leite, S., Campelo, M., Silva-Cardoso, J., Rodrigues, J., Rangel, I., Martins, E., Correia, A. S., Peres, M., Marta, L., da Silva, G. F., Severino, D., Durao, D., Leao, S., Magalhaes, P., Moreira, I., Cordeiro, A. 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C., Komel, J., Fras, Z., Jug, B., Glavic, T., Losic, R., Bombek, M., Krajnc, I., Krunic, B., Horvat, S., Kovac, D., Rajtman, D., Cencic, V., Letonja, M., Winkler, R., Valentincic, M., Melihen-Bartolic, C., Bartolic, A., Vrckovnik, M. P., Kladnik, M., Pusnik, C. S., Marolt, A., Klen, J., Drnovsek, B., Leskovar, B., Anguita, M. J. F., Page, J. C. G., Martinez, F. M. S., Andres, J., Genis, A. B., Mirabet, S., Mendez, A., Garcia-Cosio, L., Roig, E., Leon, V., Gonzalez-Costello, J., Muntane, G., Garay, A., Alcade-Martinez, V., Fernandez, S. L., Rivera-Lopez, R., Puga-Martinez, M., Fernandez-Alvarez, M., Serrano-Martinez, J. L., Grille-Cancela, Z., Marzoa-Rivas, R., Blanco-Canosa, P., Paniagua-Martin, M. J., Barge-Caballero, E., Cerdena, I. L., Baldomero, I. F. H., Padron, A. L., Rosillo, S. O., Gonzalez-Gallarza, R. D., Montanes, O. S., Manjavacas, A. M. I., Conde, A. C., Araujo, A., Soria, T., Garcia-Pavia, P., Gomez-Bueno, M., Cobo-Marcos, M., Alonso-Pulpon, L., Cubero, J. 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Bajraktari X., K., Auer, J., Ablasser, K., Fruhwald, F., Dolze, T., Brandner, K., Gstrein, S., Poelzl, G., Moertl, D., Reiter, S., Podczeck-Schweighofer, A., Muslibegovic, A., Vasilj, M., Cesko, M., Zelenika, D., Palic, B., Pravdic, D., Cuk, D., Vitlianova, K., Katova, T., Velikov, T., Kurteva, T., Gatzov, P., Kamenova, D., Antova, M., Sirakova, V., Krejci, J., Mikolaskova, M., Spinar, J., Krupicka, J., Malek, F., Hegarova, M., Lazarova, M., Monhart, Z., Hassanein, M., Sobhy, M., El Messiry, F., El Shazly, A. H., Elrakshy, Y., Youssef, A., Moneim, A. A., Noamany, M., Reda, A., Dayem, T. K. A., Farag, N., Halawa, S. I., Hamid, M. A., Said, K., Saleh, A., Ebeid, H., Hanna, R., Aziz, R., Louis, O., Enen, M. A., Ibrahim, B. S., Nasr, G., Elbahry, A., Sobhy, H., Ashmawy, M., Gouda, M., Aboleineen, W., Bernard, Y., Luporsi, P., Meneveau, N., Pillot, M., Morel, M., Seronde, M. -F., Schiele, F., Briand, F., Delahaye, F., Damy, T., de Groote, P., Fertin, M., Lamblin, N., Isnard, R., Lefol, C., Thevenin, S., Hagege, A., Jondeau, G., Logeart, D., Le Marcis, V., Ly, J. -F., Coisne, D., Lequeux, B., Le Moal, V., Mascle, S., Lotton, P., Behar, N., Donal, E., Thebault, C., Ridard, C., Reynaud, A., Basquin, A., Bauer, F., Codjia, R., Galinier, M., Tourikis, P., Stavroula, M., Tousoulis, D., Stefanadis, C., Chrysohoou, C., Kotrogiannis, I., Matzaraki, V., Dimitroula, T., Karavidas, A., Tsitsinakis, G., Kapelios, C., Nanas, J., Kampouri, H., Nana, E., Kaldara, E., Eugenidou, A., Vardas, P., Saloustros, I., Patrianakos, A., Tsaknakis, T., Evangelou, S., Nikoloulis, N., Tziourganou, H., Tsaroucha, A., Papadopoulou, A., Douras, A., Polgar, L., Merkely, B., Kosztin, A., Nyolczas, N., Nagy, A. C., Halmosi, R., Elber, J., Alony, I., Shotan, A., Fuhrmann, A. V., Amir, O., Romano, S., Marcon, S., Penco, M., Di Mauro, M., Lemme, E., Carubelli, V., Rovetta, R., Metra, M., Bulgari, M., Quinzani, F., Lombardi, C., Bosi, S., Schiavina, G., Squeri, A., Barbieri, A., Di Tano, G., Pirelli, S., Fucili, A., Passero, T., Musio, S., Di Biase, M., Correale, M., Salvemini, G., Brognoli, S., Zanelli, E., Giordano, A., Agostoni, P., Italiano, G., Salvioni, E., Copelli, S., Modena, M. G., Reggianini, L., Valenti, C., Olaru, A., Bandino, S., Deidda, M., Mercuro, G., Dessalvi, C. C., Marino, P. N., Di Ruocco, M. V., Sartori, C., Piccinino, C., Parrinello, G., Licata, G., Torres, D., Giambanco, S., Busalacchi, S., Arrotti, S., Novo, S., Inciardi, R. M., Pieri, P., Chirco, P. R., Galifi, M. A., Teresi, G., Buccheri, D., Minacapelli, A., Veniani, M., Frisinghelli, A., Priori, S. G., Cattaneo, S., Opasich, C., Gualco, A., Pagliaro, M., Mancone, M., Fedele, F., Cinque, A., Vellini, M., Scarfo, I., Romeo, F., Ferraiuolo, F., Sergi, D., Anselmi, M., Melandri, F., Leci, E., Iori, E., Bovolo, V., Pidello, S., Frea, S., Bergerone, S., Botta, M., Canavosio, F. G., Gaita, F., Merlo, M., Cinquetti, M., Sinagra, G., Ramani, F., Fabris, E., Stolfo, D., Artico, J., Miani, D., Fresco, C., Daneluzzi, C., Proclemer, A., Cicoira, M., Zanolla, L., Marchese, G., Torelli, F., Vassanelli, C., Voronina, N., Erglis, A., Tamakauskas, V., Smalinskas, V., Karaliute, R., Petraskiene, I., Kazakauskaite, E., Rumbinaite, E., Kavoliuniene, A., Vysniauskas, V., Brazyte-Ramanauskiene, R., Petraskiene, D., Stankala, S., Switala, P., Juszczyk, Z., Sinkiewicz, W., Gilewski, W., Pietrzak, J., Orzel, T., Kasztelowicz, P., Kardaszewicz, P., Lazorko-Piega, M., Gabryel, J., Mosakowska, K., Bellwon, J., Rynkiewicz, A., Raczak, G., Lewicka, E., Dabrowska-Kugacka, A., Bartkowiak, R., Sosnowska-Pasiarska, B., Wozakowska-Kaplon, B., Krzeminski, A., Zabojszcz, M., Mirek-Bryniarska, E., Grzegorzko, A., Bury, K., Nessler, J., Zalewski, J., Furman, A., Broncel, M., Poliwczak, A., Bala, A., Zycinski, P., Rudzinska, M., Jankowski, L., Kasprzak, J. D., Michalak, L., Soska, K. W., Drozdz, J., Huziuk, I., Retwinski, A., Flis, P., Weglarz, J., Bodys, A., Grajek, S., Kaluzna-Oleksy, M., Straburzynska-Migaj, E., Dankowski, R., Szymanowska, K., Grabia, J., Szyszka, A., Nowicka, A., Samcik, M., Wolniewicz, L., Baczynska, K., Komorowska, K., Poprawa, I., Komorowska, E., Sajnaga, D., Zolbach, A., Dudzik-Plocica, A., Abdulkarim, A. -F., Lauko-Rachocka, A., Kaminski, L., Kostka, A., Cichy, A., Ruszkowski, P., Splawski, M., Fitas, G., Szymczyk, A., Serwicka, A., Fiega, A., Zysko, D., Krysiak, W., Szabowski, S., Skorek, E., Pruszczyk, P., Bienias, P., Ciurzynski, M., Welnicki, M., Mamcarz, A., Folga, A., Zielinski, T., Rywik, T., Leszek, P., Sobieszczanska-Malek, M., Piotrowska, M., Kozar-Kaminska, K., Komuda, K., Wisniewska, J., Tarnowska, A., Balsam, P., Marchel, M., Opolski, G., Kaplon-Cieslicka, A., Gil, R. J., Mozenska, O., Byczkowska, K., Gil, K., Pawlak, A., Michalek, A., Krzesinski, P., Piotrowicz, K., Uzieblo-Zyczkowska, B., Stanczyk, A., Skrobowski, A., Ponikowski, P., Jankowska, E., Rozentryt, P., Polonski, L., Gadula-Gacek, E., Nowalany-Kozielska, E., Kuczaj, A., Kalarus, Z., Szulik, M., Przybylska, K., Klys, J., Prokop-Lewicka, G., Kleinrok, A., Aguiar, C. T., Ventosa, A., Pereira, S., Faria, R., Chin, J., De Jesus, I., Santos, R., Silva, P., Moreno, N., Queiros, C., Lourenco, C., Pereira, A., Castro, A., Andrade, A., Guimaraes, T. O., Martins, S., Placido, R., Lima, G., Brito, D., Francisco, A. R., Cardiga, R., Proenca, M., Araujo, I., Marques, F., Moura, B., Leite, S., Campelo, M., Silva-Cardoso, J., Rodrigues, J., Rangel, I., Martins, E., Correia, A. S., Peres, M., Marta, L., da Silva, G. F., Severino, D., Durao, D., Leao, S., Magalhaes, P., Moreira, I., Cordeiro, A. F., Ferreira, C., Araujo, C., Ferreira, A., Baptista, A., Radoi, M., Bicescu, G., Vinereanu, D., Sinescu, C. -J., Macarie, C., Popescu, R., Daha, I., Dan, G. -A., Stanescu, C., Dan, A., Craiu, E., Nechita, E., Aursulesei, V., Christodorescu, R., Otasevic, P., Simeunovic, D., Ristic, A. D., Celic, V., Pavlovic-Kleut, M., Lazic, J. S., Stojcevski, B., Pencic, B., Stevanovic, A., Andric, A., Iric-Cupic, V., Jovic, M., Davidovic, G., Milanov, S., Mitic, V., Atanaskovic, V., Antic, S., Pavlovic, M., Stanojevic, D., Stoickov, V., Ilic, S., Ilic, M. D., Petrovic, D., Stojsic, S., Kecojevic, S., Dodic, S., Adic, N. C., Cankovic, M., Stojiljkovic, J., Mihajlovic, B., Radin, A., Radovanovic, S., Krotin, M., Klabnik, A., Goncalvesova, E., Pernicky, M., Murin, J., Kovar, F., Kmec, J., Semjanova, H., Strasek, M., Iskra, M. S., Ravnikar, T., Suligoj, N. C., Komel, J., Fras, Z., Jug, B., Glavic, T., Losic, R., Bombek, M., Krajnc, I., Krunic, B., Horvat, S., Kovac, D., Rajtman, D., Cencic, V., Letonja, M., Winkler, R., Valentincic, M., Melihen-Bartolic, C., Bartolic, A., Vrckovnik, M. P., Kladnik, M., Pusnik, C. S., Marolt, A., Klen, J., Drnovsek, B., Leskovar, B., Anguita, M. J. F., Page, J. C. G., Martinez, F. M. S., Andres, J., Genis, A. B., Mirabet, S., Mendez, A., Garcia-Cosio, L., Roig, E., Leon, V., Gonzalez-Costello, J., Muntane, G., Garay, A., Alcade-Martinez, V., Fernandez, S. L., Rivera-Lopez, R., Puga-Martinez, M., Fernandez-Alvarez, M., Serrano-Martinez, J. L., Grille-Cancela, Z., Marzoa-Rivas, R., Blanco-Canosa, P., Paniagua-Martin, M. J., Barge-Caballero, E., Cerdena, I. L., Baldomero, I. F. H., Padron, A. L., Rosillo, S. O., Gonzalez-Gallarza, R. D., Montanes, O. S., Manjavacas, A. M. I., Conde, A. C., Araujo, A., Soria, T., Garcia-Pavia, P., Gomez-Bueno, M., Cobo-Marcos, M., Alonso-Pulpon, L., Cubero, J. S., Sayago, I., Gonzalez-Segovia, A., Briceno, A., Subias, P. E., Hernandez, M. V., Cano, M. J. R., Sanchez, M. A. G., Jimenez, J. F. D., Garrido-Lestache, E. B., Pinilla, J. M. G., de la Villa, B. G., Sahuquillo, A., Marques, R. B., Calvo, F. T., Perez-Martinez, M. T., Gracia-Rodenas, M. R., Garrido-Bravo, I. P., Pastor-Perez, F., Pascual-Figal, D. A., Molina, B. D., Orus, J., Gonzalo, F. E., Bertomeu, V., Valero, R., Martinez-Abellan, R., Quiles, J., Rodrigez-Ortega, J. A., Mateo, I., Elamrani, A., Fernandez-Vivancos, C., Valero, D. B., Almenar-Bonet, L., Sanchez-Lazaro, I. J., Marques-Sule, E., Facila-Rubio, L., Perez-Silvestre, J., Garcia-Gonzalez, P., Ridocci-Soriano, F., Garcia-Escriva, D., Pellicer-Cabo, A., de la Fuente Galan, L., Diaz, J. L., Platero, A. R., Arias, J. C., Blasco-Peiro, T., Julve, M. S., Sanchez-Insa, E., Aured-Guallar, C., Portoles-Ocampo, A., Melin, M., Hagglund, E., Stenberg, A., Lindahl, I. -M., Asserlund, B., Olsson, L., Dahlstrom, U., Afzelius, M., Karlstrom, P., Tengvall, L., Wiklund, P. -A., Olsson, B., Kalayci, S., Temizhan, A., Cavusoglu, Y., Gencer, E., Gunes, H., University of Zurich, and Seferović, Petar M
Subjects: Male, Registry, medicine.medical_specialty, Adverse outcomes, 610 Medicine & health, Angiotensin-Converting Enzyme Inhibitors, 030204 cardiovascular system & hematology, Independent predictor, 2705 Cardiology and Cardiovascular Medicine, Ventricular Function, Left, 03 medical and health sciences, Age, 0302 clinical medicine, Internal medicine, Age related, Hospitalization, Mortality, Sex, medicine, Humans, Registries, Medical prescription, Aged, Heart Failure, Ejection fraction, business.industry, Stroke Volume, medicine.disease, Ageing, Heart failure, 10209 Clinic for Cardiology, Female, Angiotensin Receptor Blockers, Cardiology and Cardiovascular Medicine, business
Abstract: [Abstract] Aims. This study aimed to assess age‐ and sex‐related differences in management and 1‐year risk for all‐cause mortality and hospitalization in chronic heart failure (HF) patients. Methods and results. Of 16 354 patients included in the European Society of Cardiology Heart Failure Long‐Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline‐directed medical therapy (GDMT) were high (angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers, beta‐blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P ≤ 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1‐year follow‐up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all‐cause mortality were lower in women than in men (7.1% vs. 8.7%; P = 0.015), as were rates of all‐cause hospitalization (21.9% vs. 27.3%; P < 0.001) and there were no differences in causes of death. All‐cause mortality and all‐cause hospitalization increased with greater age in both sexes. Sex was not an independent predictor of 1‐year all‐cause mortality (restricted to patients with LVEF ≤45%). Mortality risk was significantly lower in patients of younger age, compared to patients aged >75 years. Conclusions. There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all‐cause mortality in patients with LVEF ≤45%.
Published: 2019
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5. Unravelling the interplay between hyperkalaemia, renin-angiotensin-aldosterone inhibitor use and clinical outcomes. Data from 9222 chronic heart failure patients of the ESC-HFA-EORP Heart Failure Long-Term Registry

Author: Rossignol, P., Lainscak, M., Crespo-Leiro, M. G., Laroche, C., Piepoli, M. F., Filippatos, G., Rosano, G. M. C., Savarese, G., Anker, S. D., Seferovic, P. M., Ruschitzka, F., Coats, A. J. S., Mebazaa, A., Mcdonagh, T., Sahuquillo, A., Penco, M., Maggioni, A. P., Lund, L. H., Christopher Peter Gale, G. B., Branko Beleslin, R. S., Andrzej Budaj, P. L., Ovidiu Chioncel, R. O., Nikolaos Dagres, D. E., Nicolas Danchin, F. R., David Erlinge, S. E., Jonathan Emberson, G. B., Michael Glikson, I. L., Alastair Gray, G. B., Meral Kayikcioglu, T. R., Aldo Maggioni, I. T., Klaudia Vivien Nagy, H. U., Aleksandr Nedoshivin, R. U., Anna-Sonia Petronio, I. T., Jolien Roos-Hesselink, N. L., Lars Wallentin, S. E., Uwe Zeymer, D. E., Crespo-Leiro, M., Anker, S., Coats, A., Ferrari, R., Goda, A., Diez, M., Fernandez, A., Fruhwald, F., Fazlibegovic, E., Gatzov, P., Kurlianskaya, A., Hullin, R., Christodoulides, T., Hradec, J., Nielsen, O. W., Nedjar, R., Uuetoa, T., Hassanein, M., Jimenez, J. F. D., Harjola, V. P., Logeart, D., Chumburidze, V., Tousoulis, D., Milicic, D., Merkely, B., O'Donoghue, E., Amir, O., Shotan, A., Shafie, D., Metra, M., Matsumori, A., Mirrakhimov, E., Kavoliuniene, A., Erglis, A., Vataman, E., Otljanska, M., Kostovska, E. S., Demarco, D. C., Drozdz, J., Fonseca, C., Chioncel, O., Dekleva, M., Shkolnik, E., Dahlstrom, U., Goncalvesova, E., Temizhan, A., Estrago, V., Bajraktari, G., Auer, J., Ablasser, K., Dolze, T., Brandner, K., Gstrein, S., Poelzl, G., Moertl, D., Reiter, S., Podczeck-Schweighofer, A., Muslibegovic, A., Vasilj, M., Cesko, M., Zelenika, D., Palic, B., Pravdic, D., Cuk, D., Vitlianova, K., Katova, T., Velikov, T., Kurteva, T., Kamenova, D., Antova, M., Sirakova, V., Krejci, J., Mikolaskova, M., Spinar, J., Krupicka, J., Malek, F., Hegarova, M., Lazarova, M., Monhart, Z., Sobhy, M., El Messiry, F., El Shazly, A. H., Elrakshy, Y., Youssef, A., Moneim, A. A., Noamany, M., Reda, A., Dayem, T. K. A., Farag, N., Halawa, S. I., Hamid, M. A., Said, K., Saleh, A., Ebeid, H., Hanna, R., Aziz, R., Louis, O., Enen, M. A., Ibrahim, B. 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V., Romano, S., Marcon, S., Di Mauro, M., Lemme, E., Carubelli, V., Rovetta, R., Bulgari, M., Quinzani, F., Lombardi, C., Bosi, S., Schiavina, G., Squeri, A., Barbieri, A., Di Tano, G., Pirelli, S., Fucili, A., Passero, T., Musio, S., Di Biase, M., Correale, M., Salvemini, G., Brognoli, S., Zanelli, E., Giordano, A., Agostoni, P., Italiano, G., Salvioni, E., Copelli, S., Modena, M. G., Reggianini, L., Valenti, C., Olaru, A., Bandino, S., Deidda, M., Mercuro, G., Dessalvi, C. C., Marino, P. N., Di Ruocco, M. V., Sartori, C., Piccinino, C., Parrinello, G., Licata, G., Torres, D., Giambanco, S., Busalacchi, S., Arrotti, S., Novo, S., Inciardi, R. M., Pieri, P., Chirco, P. R., Galifi, M. A., Teresi, G., Buccheri, D., Minacapelli, A., Veniani, M., Frisinghelli, A., Priori, S. 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J., Mozenska, O., Byczkowska, K., Gil, K., Pawlak, A., Michalek, A., Krzesinski, P., Piotrowicz, K., Uzieblo-Zyczkowska, B., Stanczyk, A., Skrobowski, A., Ponikowski, P., Jankowska, E., Rozentryt, P., Polonski, L., Gadula-Gacek, E., Nowalany-Kozielska, E., Kuczaj, A., Kalarus, Z., Szulik, M., Przybylska, K., Klys, J., Prokop-Lewicka, G., Kleinrok, A., Aguiar, C. T., Ventosa, A., Pereira, S., Faria, R., Chin, J., De Jesus, I., Santos, R., Silva, P., Moreno, N., Queiros, C., Lourenco, C., Pereira, A., Castro, A., Andrade, A., Guimaraes, T. O., Martins, S., Placido, R., Lima, G., Brito, D., Francisco, A. R., Cardiga, R., Proenca, M., Araujo, I., Marques, F., Moura, B., Leite, S., Campelo, M., Silva-Cardoso, J., Rodrigues, J., Rangel, I., Martins, E., Correia, A. S., Peres, M., Marta, L., da Silva, G. F., Severino, D., Durao, D., Leao, S., Magalhaes, P., Moreira, I., Cordeiro, A. F., Ferreira, C., Araujo, C., Ferreira, A., Baptista, A., Radoi, M., Bicescu, G., Vinereanu, D., Sinescu, C. -J., Macarie, C., Popescu, R., Daha, I., Dan, G. -A., Stanescu, C., Dan, A., Craiu, E., Nechita, E., Aursulesei, V., Christodorescu, R., Otasevic, P., Simeunovic, D., Ristic, A. D., Celic, V., Pavlovic-Kleut, M., Lazic, J. S., Stojcevski, B., Pencic, B., Stevanovic, A., Andric, A., Simic, D., Asanin, M., Iric-Cupic, V., Jovic, M., Davidovic, G., Milanov, S., Mitic, V., Atanaskovic, V., Antic, S., Pavlovic, M., Stanojevic, D., Stoickov, V., Ilic, S., Ilic, M. D., Petrovic, D., Stojsic, S., Kecojevic, S., Dodic, S., Adic, N. C., Cankovic, M., Stojiljkovic, J., Mihajlovic, B., Radin, A., Radovanovic, S., Krotin, M., Klabnik, A., Pernicky, M., Murin, J., Kovar, F., Kmec, J., Semjanova, H., Strasek, M., Iskra, M. S., Ravnikar, T., Suligoj, N. C., Komel, J., Fras, Z., Jug, B., Glavic, T., Losic, R., Bombek, M., Krajnc, I., Krunic, B., Horvat, S., Kovac, D., Rajtman, D., Cencic, V., Letonja, M., Winkler, R., Valentincic, M., Melihen-Bartolic, C., Bartolic, A., Vrckovnik, M. P., Kladnik, M., Pusnik, C. S., Marolt, A., Klen, J., Drnovsek, B., Leskovar, B., Anguita, M. J. F., Page, J. C. G., Martinez, F. M. S., Andres, J., Bayes-Genis, A., Mirabet, S., Mendez, A., Garcia-Cosio, L., Roig, E., Leon, V., Gonzalez-Costello, J., Muntane, G., Garay, A., Alcade-Martinez, V., Fernandez, S. L., Rivera-Lopez, R., Puga-Martinez, M., Fernandez-Alvarez, M., Serrano-Martinez, J. L., Grille-Cancela, Z., Marzoa-Rivas, R., Blanco-Canosa, P., Paniagua-Martin, M. J., Barge-Caballero, E., Cerdena, I. L., Baldomero, I. F. H., Padron, A. L., Rosillo, S. O., Gonzalez-Gallarza, R. D., Montanes, O. S., Manjavacas, A. M. I., Conde, A. C., Araujo, A., Soria, T., Garcia-Pavia, P., Gomez-Bueno, M., Cobo-Marcos, M., Alonso-Pulpon, L., Cubero, J. S., Sayago, I., Gonzalez-Segovia, A., Briceno, A., Subias, P. E., Hernandez, M. V., Cano, M. J. R., Sanchez, M. A. G., Garrido-Lestache, E. B., Pinilla, J. M. G., de la Villa, B. G., Marques, R. B., Calvo, F. T., Perez-Martinez, M. T., Gracia-Rodenas, M. R., Garrido-Bravo, I. P., Pastor-Perez, F., Pascual-Figal, D. A., Molina, B. D., Orus, J., Gonzalo, F. E., Bertomeu, V., Valero, R., Martinez-Abellan, R., Quiles, J., Rodrigez-Ortega, J. A., Mateo, I., Elamrani, A., Fernandez-Vivancos, C., Valero, D. B., Almenar-Bonet, L., Sanchez-Lazaro, I. J., Marques-Sule, E., Facila-Rubio, L., Perez-Silvestre, J., Garcia-Gonzalez, P., Ridocci-Soriano, F., Garcia-Escriva, D., Pellicer-Cabo, A., de la Fuente Galan, L., Diaz, J. L., Platero, A. R., Arias, J. C., Blasco-Peiro, T., Julve, M. S., Sanchez-Insa, E., Aured-Guallar, C., Portoles-Ocampo, A., Melin, M., Hagglund, E., Stenberg, A., Lindahl, I. -M., Asserlund, B., Olsson, L., Afzelius, M., Karlstrom, P., Tengvall, L., Olsson, B., Kalayci, S., Cavusoglu, Y., Gencer, E., Yilmaz, M. B., Gunes, H., Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), University of Ljubljana, University of A Coruña (UDC), EURObservational Research Programme, European Society of Cardiology, Cardiac Department, G. da Saliceto Hospital, AUSL Piacenza, National and Kapodistrian University of Athens (NKUA), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS San Raffaele Pisana), Karolinska Institutet [Stockholm], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Berlin-Brandenburg Center for Regenerative Medicine [Berlin, Germany] (BCRT), University hospital of Zurich [Zurich], Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Université Sorbonne Paris Nord, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), King's College Hospital (KCH), Hospital de Manacor, Università degli Studi dell'Aquila (UNIVAQ), ANMCO Research Center, Firenze,Italy, Since the start of EORP, the following companies have supported the programme: Abbott Vascular Int. (2011-2021), Amgen Cardiovascular (2009-2018), AstraZeneca (2014-2021), Bayer AG (2009-2018), Boehringer Ingelheim (2009-2019), Boston Scientific (2009-2012), The Bristol Myers Squibb and Pfizer Alliance (2011-2019), Daiichi Sankyo Europe GmbH (2011-2020), The Alliance Daiichi Sankyo Europe GmbH and Eli Lilly and Company (2014-2017), Edwards (2016-2019), Gedeon Richter Plc. (2014-2016), Menarini Int. Op. (2009-2012), MSD-Merck & Co. (2011-2014), Novartis Pharma AG (2014-2020), ResMed (2014-2016), Sanofi (2009-2011), SERVIER (2009-2018), Vifor (2019-2022)., Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), and Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)
Subjects: medicine.medical_specialty, Angiotensin receptor, Angiotensins, Prognosi, Angiotensin-Converting Enzyme Inhibitors, Heart failure, 610 Medicine & health, 030204 cardiovascular system & hematology, Hyperkalaemia, Hypokalaemia, Mineralocorticoid receptor antagonists, Prognosis, Renin–angiotensin–aldosterone system inhibitors, 2705 Cardiology and Cardiovascular Medicine, Angiotensin Receptor Antagonists, 03 medical and health sciences, 0302 clinical medicine, Mineralocorticoid receptor, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Renin, Renin–angiotensin system, Humans, Medicine, Registries, cardiovascular diseases, Risk factor, Aldosterone, Ejection fraction, business.industry, Mineralocorticoid receptor antagonist, Renin-angiotensin-aldosterone system inhibitors, medicine.disease, 3. Good health, Discontinuation, Cardiology, 10209 Clinic for Cardiology, Hyperkalemia, Cardiology and Cardiovascular Medicine, business, Lower mortality
Abstract: [Abstract] Aims. We assessed the interplay between hyperkalaemia (HK) and renin–angiotensin–aldosterone system inhibitor (RAASi) use, dose and discontinuation, and their association with all‐cause or cardiovascular death in patients with chronic heart failure (HF). We hypothesized that HK‐associated increased death may be related to RAASi withdrawal. Methods and results. The ESC‐HFA‐EORP Heart Failure Long‐Term Registry was used. Among 9222 outpatients (HF with reduced ejection fraction: 60.6%, HF with mid‐range ejection fraction: 22.9%, HF with preserved ejection fraction: 16.5%) from 31 countries, 16.6% had HK (≥5.0 mmol/L) at baseline. Angiotensin‐converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) was used in 88.3%, a mineralocorticoid receptor antagonist (MRA) in 58.7%, or a combination in 53.2%; of these, at ≥50% of target dose in ACEi: 61.8%; ARB: 64.7%; and MRA: 90.3%. At a median follow‐up of 12.2 months, there were 789 deaths (8.6%). Both hypokalaemia and HK were independently associated with higher mortality, and ACEi/ARB prescription at baseline with lower mortality. MRA prescription was not retained in the model. In multivariable analyses, HK at baseline was independently associated with MRA non‐prescription at baseline and subsequent discontinuation. When considering subsequent discontinuation of RAASi (instead of baseline use), HK was no longer found associated with all‐cause deaths. Importantly, all RAASi (ACEi, ARB, or MRA) discontinuations were strongly associated with mortality. Conclusions. In HF, hyper‐ and hypokalaemia were associated with mortality. However, when adjusting for RAASi discontinuation, HK was no longer associated with mortality, suggesting that HK may be a risk marker for RAASi discontinuation rather than a risk factor for worse outcomes. Funding for open access charge: Universidad de Granada / CBUA. The work was funded by the Courel Mountains UGGp
Published: 2020
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6. First large rearrangement in the MUTYH gene and attenuated familial adenomatous polyposis syndrome

Author: Rouleau, E, Zattara, H, Lefol, C, Noguchi, T, Briaux, A, Buecher, B, Bourdon, V, Sobol, H, Lidereau, R, and Olschwang, S
Published: 2011
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7. Acute heart failure congestion and perfusion status – impact of the clinical classification on in-hospital and long-term outcomes; insights from the ESC-EORP-HFA Heart Failure Long-Term Registry

Author: Chioncel, O., Mebazaa, A., Maggioni, A. P., Harjola, V. -P., Rosano, G., Laroche, C., Piepoli, M. F., Crespo-Leiro, M. G., Lainscak, M., Ponikowski, P., Filippatos, G., Ruschitzka, F., Seferovic, P., Coats, A. J. S., Lund, L. H., Auer, J., Ablasser, K., Fruhwald, F., Dolze, T., Brandner, K., Gstrein, S., Poelzl, G., Moertl, D., Reiter, S., Podczeck-Schweighofer, A., Muslibegovic, A., Vasilj, M., Fazlibegovic, E., Cesko, M., Zelenika, D., Palic, B., Pravdic, D., Cuk, D., Vitlianova, K., Katova, T., Velikov, T., Kurteva, T., Gatzov, P., Kamenova, D., Antova, M., Sirakova, V., Krejci, J., Mikolaskova, M., Spinar, J., Krupicka, J., Malek, F., Hegarova, M., Lazarova, M., Monhart, Z., Hassanein, M., Sobhy, M., El Messiry, F., El Shazly, A. H., Elrakshy, Y., Youssef, A., Moneim, A. A., Noamany, M., Reda, A., Dayem, T. K. A., Farag, N., Halawa, S. I., Hamid, M. A., Said, K., Saleh, A., Ebeid, H., Hanna, R., Aziz, R., Louis, O., Enen, M. A., Ibrahim, B. S., Nasr, G., Elbahry, A., Sobhy, H., Ashmawy, M., Gouda, M., Aboleineen, W., Bernard, Y., Luporsi, P., Meneveau, N., Pillot, M., Morel, M., Seronde, M. -F., Schiele, F., Briand, F., Delahaye, F., Damy, T., Eicher, J. -C., de Groote, P., Fertin, M., Lamblin, N., Isnard, R., Lefol, C., Thevenin, S., Hagege, A., Jondeau, G., Logeart, D., Le Marcis, V., J. -F., Ly, Coisne, D., Lequeux, B., Le Moal, V., Mascle, S., Lotton, P., Behar, N., Donal, E., Thebault, C., Ridard, C., Reynaud, A., Basquin, A., Bauer, F., Codjia, R., Galinier, M., Tourikis, P., Stavroula, M., Tousoulis, D., Stefanadis, C., Chrysohoou, C., Kotrogiannis, I., Matzaraki, V., Dimitroula, T., Karavidas, A., Tsitsinakis, G., Kapelios, C., Nanas, J., Kampouri, H., Nana, E., Kaldara, E., Eugenidou, A., Vardas, P., Saloustros, I., Patrianakos, A., Tsaknakis, T., Evangelou, S., Nikoloulis, N., Tziourganou, H., Tsaroucha, A., Papadopoulou, A., Douras, A., Polgar, L., Merkely, B., Kosztin, A., Nyolczas, N., Nagy, A. C., Halmosi, R., Elber, J., Alony, I., Shotan, A., Fuhrmann, A. V., Amir, O., Romano, S., Marcon, S., Penco, M., Di Mauro, M., Lemme, E., Carubelli, V., Rovetta, R., Metra, M., Bulgari, M., Quinzani, F., Lombardi, C., Bosi, S., Schiavina, G., Squeri, A., Barbieri, A., Di Tano, G., Pirelli, S., Ferrari, R., Fucili, A., Passero, T., Musio, S., Di Biase, M., Correale, M., Salvemini, G., Brognoli, S., Zanelli, E., Giordano, A., Agostoni, P., Italiano, G., Salvioni, E., Copelli, S., Modena, M. G., Reggianini, L., Valenti, C., Olaru, A., Bandino, S., Deidda, M., Mercuro, G., Dessalvi, C. C., Marino, P. N., Di Ruocco, M. V., Sartori, C., Piccinino, C., Parrinello, G., Licata, G., Torres, D., Giambanco, S., Busalacchi, S., Arrotti, S., Novo, S., Inciardi, R. M., Pieri, P., Chirco, P. R., Galifi, M. A., Teresi, G., Buccheri, D., Minacapelli, A., Veniani, M., Frisinghelli, A., Priori, S. G., Cattaneo, S., Opasich, C., Gualco, A., Pagliaro, M., Mancone, M., Fedele, F., Cinque, A., Vellini, M., Scarfo, I., Romeo, F., Ferraiuolo, F., Sergi, D., Anselmi, M., Melandri, F., Leci, E., Iori, E., Bovolo, V., Pidello, S., Frea, S., Bergerone, S., Botta, M., Canavosio, F. G., Gaita, F., Merlo, M., Cinquetti, M., Sinagra, G., Ramani, F., Fabris, E., Stolfo, D., Artico, J., Miani, D., Fresco, C., Daneluzzi, C., Proclemer, A., Cicoira, M., Zanolla, L., Marchese, G., Torelli, F., Vassanelli, C., Voronina, N., Erglis, A., Tamakauskas, V., Smalinskas, V., Karaliute, R., Petraskiene, I., Kazakauskaite, E., Rumbinaite, E., Kavoliuniene, A., Vysniauskas, V., Brazyte-Ramanauskiene, R., Petraskiene, D., Stankala, S., Switala, P., Juszczyk, Z., Sinkiewicz, W., Gilewski, W., Pietrzak, J., Orzel, T., Kasztelowicz, P., Kardaszewicz, P., Lazorko-Piega, M., Gabryel, J., Mosakowska, K., Bellwon, J., Rynkiewicz, A., Raczak, G., Lewicka, E., Dabrowska-Kugacka, A., Bartkowiak, R., Sosnowska-Pasiarska, B., Wozakowska-Kaplon, B., Krzeminski, A., Zabojszcz, M., Mirek-Bryniarska, E., Grzegorzko, A., Bury, K., Nessler, J., Zalewski, J., Furman, A., Broncel, M., Poliwczak, A., Bala, A., Zycinski, P., Rudzinska, M., Jankowski, L., Kasprzak, J. D., Michalak, L., Soska, K. W., Drozdz, J., Huziuk, I., Retwinski, A., Flis, P., Weglarz, J., Bodys, A., Grajek, S., Kaluzna-Oleksy, M., Straburzynska-Migaj, E., Dankowski, R., Szymanowska, K., Grabia, J., Szyszka, A., Nowicka, A., Samcik, M., Wolniewicz, L., Baczynska, K., Komorowska, K., Poprawa, I., Komorowska, E., Sajnaga, D., Zolbach, A., Dudzik-Plocica, A., Abdulkarim, A. -F., Lauko-Rachocka, A., Kaminski, L., Kostka, A., Cichy, A., Ruszkowski, P., Splawski, M., Fitas, G., Szymczyk, A., Serwicka, A., Fiega, A., Zysko, D., Krysiak, W., Szabowski, S., Skorek, E., Pruszczyk, P., Bienias, P., Ciurzynski, M., Welnicki, M., Mamcarz, A., Folga, A., Zielinski, T., Rywik, T., Leszek, P., Sobieszczanska-Malek, M., Piotrowska, M., Kozar-Kaminska, K., Komuda, K., Wisniewska, J., Tarnowska, A., Balsam, P., Marchel, M., Opolski, G., Kaplon-Cieslicka, A., Gil, R. J., Mozenska, O., Byczkowska, K., Gil, K., Pawlak, A., Michalek, A., Krzesinski, P., Piotrowicz, K., Uzieblo-Zyczkowska, B., Stanczyk, A., Skrobowski, A., Jankowska, E., Rozentryt, P., Polonski, L., Gadula-Gacek, E., Nowalany-Kozielska, E., Kuczaj, A., Kalarus, Z., Szulik, M., Przybylska, K., Klys, J., Prokop-Lewicka, G., Kleinrok, A., Aguiar, C. T., Ventosa, A., Pereira, S., Faria, R., Chin, J., De Jesus, I., Santos, R., Silva, P., Moreno, N., Queiros, C., Lourenco, C., Pereira, A., Castro, A., Andrade, A., Guimaraes, T. O., Martins, S., Placido, R., Lima, G., Brito, D., Francisco, A. R., Cardiga, R., Proenca, M., Araujo, I., Marques, F., Fonseca, C., Moura, B., Leite, S., Campelo, M., Silva-Cardoso, J., Rodrigues, J., Rangel, I., Martins, E., Correia, A. S., Peres, M., Marta, L., da Silva, G. F., Severino, D., Durao, D., Leao, S., Magalhaes, P., Moreira, I., Cordeiro, A. F., Ferreira, C., Araujo, C., Ferreira, A., Baptista, A., Radoi, M., Bicescu, G., Vinereanu, D., Sinescu, C. -J., Macarie, C., Popescu, R., Daha, I., Dan, G. -A., Stanescu, C., Dan, A., Craiu, E., Nechita, E., Aursulesei, V., Christodorescu, R., Otasevic, P., Seferovic, P. M., Simeunovic, D., Ristic, A. D., Celic, V., Pavlovic-Kleut, M., Lazic, J. S., Stojcevski, B., Pencic, B., Stevanovic, A., Andric, A., Iric-Cupic, V., Jovic, M., Davidovic, G., Milanov, S., Mitic, V., Atanaskovic, V., Antic, S., Pavlovic, M., Stanojevic, D., Stoickov, V., Ilic, S., Ilic, M. D., Petrovic, D., Stojsic, S., Kecojevic, S., Dodic, S., Adic, N. C., Cankovic, M., Stojiljkovic, J., Mihajlovic, B., Radin, A., Radovanovic, S., Krotin, M., Klabnik, A., Goncalvesova, E., Pernicky, M., Murin, J., Kovar, F., Kmec, J., Semjanova, H., Strasek, M., Iskra, M. S., Ravnikar, T., Suligoj, N. C., Komel, J., Fras, Z., Jug, B., Glavic, T., Losic, R., Bombek, M., Krajnc, I., Krunic, B., Horvat, S., Kovac, D., Rajtman, D., Cencic, V., Letonja, M., Winkler, R., Valentincic, M., Melihen-Bartolic, C., Bartolic, A., Vrckovnik, M. P., Kladnik, M., Pusnik, C. S., Marolt, A., Klen, J., Drnovsek, B., Leskovar, B., Anguita, M. J. F., Page, J. C. G., Martinez, F. M. S., Andres, J., Genis, A. B., Mirabet, S., Mendez, A., Garcia-Cosio, L., Roig, E., Leon, V., Gonzalez-Costello, J., Muntane, G., Garay, A., Alcade-Martinez, V., Fernandez, S. L., Rivera-Lopez, R., Puga-Martinez, M., Fernandez-Alvarez, M., Serrano-Martinez, J. L., Crespo-Leiro, M., Grille-Cancela, Z., Marzoa-Rivas, R., Blanco-Canosa, P., Paniagua-Martin, M. J., Barge-Caballero, E., Cerdena, I. L., Baldomero, I. F. H., Padron, A. L., Rosillo, S. O., Gonzalez-Gallarza, R. D., Montanes, O. S., Manjavacas, A. M. I., Conde, A. C., Araujo, A., Soria, T., Garcia-Pavia, P., Gomez-Bueno, M., Cobo-Marcos, M., Alonso-Pulpon, L., Cubero, J. S., Sayago, I., Gonzalez-Segovia, A., Briceno, A., Subias, P. E., Hernandez, M. V., Cano, M. J. R., Sanchez, M. A. G., Jimenez, J. F. D., Garrido-Lestache, E. B., Pinilla, J. M. G., de la Villa, B. G., Sahuquillo, A., Marques, R. B., Calvo, F. T., Perez-Martinez, M. T., Gracia-Rodenas, M. R., Garrido-Bravo, I. P., Pastor-Perez, F., Pascual-Figal, D. A., Molina, B. D., Orus, J., Gonzalo, F. E., Bertomeu, V., Valero, R., Martinez-Abellan, R., Quiles, J., Rodrigez-Ortega, J. A., Mateo, I., Elamrani, A., Fernandez-Vivancos, C., Valero, D. B., Almenar-Bonet, L., Sanchez-Lazaro, I. J., Marques-Sule, E., Facila-Rubio, L., Perez-Silvestre, J., Garcia-Gonzalez, P., Ridocci-Soriano, F., Garcia-Escriva, D., Pellicer-Cabo, A., de la Fuente Galan, L., Diaz, J. L., Platero, A. R., Arias, J. C., Blasco-Peiro, T., Julve, M. S., Sanchez-Insa, E., Aured-Guallar, C., Portoles-Ocampo, A., Melin, M., Hagglund, E., Stenberg, A., Lindahl, I. -M., Asserlund, B., Olsson, L., Dahlstrom, U., Afzelius, M., Karlstrom, P., Tengvall, L., Wiklund, P. -A., Olsson, B., Kalayci, S., Temizhan, A., Cavusoglu, Y., Gencer, E., Yilmaz, M. B., Gunes, H., Chioncel, O., Mebazaa, A., Maggioni, A. P., Harjola, V. -P., Rosano, G., Laroche, C., Piepoli, M. F., Crespo-Leiro, M. G., Lainscak, M., Ponikowski, P., Filippatos, G., Ruschitzka, F., Seferovic, P., Coats, A. J. S., Lund, L. H., Auer, J., Ablasser, K., Fruhwald, F., Dolze, T., Brandner, K., Gstrein, S., Poelzl, G., Moertl, D., Reiter, S., Podczeck-Schweighofer, A., Muslibegovic, A., Vasilj, M., Fazlibegovic, E., Cesko, M., Zelenika, D., Palic, B., Pravdic, D., Cuk, D., Vitlianova, K., Katova, T., Velikov, T., Kurteva, T., Gatzov, P., Kamenova, D., Antova, M., Sirakova, V., Krejci, J., Mikolaskova, M., Spinar, J., Krupicka, J., Malek, F., Hegarova, M., Lazarova, M., Monhart, Z., Hassanein, M., Sobhy, M., El Messiry, F., El Shazly, A. H., Elrakshy, Y., Youssef, A., Moneim, A. A., Noamany, M., Reda, A., Dayem, T. K. A., Farag, N., Halawa, S. I., Hamid, M. A., Said, K., Saleh, A., Ebeid, H., Hanna, R., Aziz, R., Louis, O., Enen, M. A., Ibrahim, B. S., Nasr, G., Elbahry, A., Sobhy, H., Ashmawy, M., Gouda, M., Aboleineen, W., Bernard, Y., Luporsi, P., Meneveau, N., Pillot, M., Morel, M., Seronde, M. -F., Schiele, F., Briand, F., Delahaye, F., Damy, T., Eicher, J. -C., de Groote, P., Fertin, M., Lamblin, N., Isnard, R., Lefol, C., Thevenin, S., Hagege, A., Jondeau, G., Logeart, D., Le Marcis, V., Ly, J. -F., Coisne, D., Lequeux, B., Le Moal, V., Mascle, S., Lotton, P., Behar, N., Donal, E., Thebault, C., Ridard, C., Reynaud, A., Basquin, A., Bauer, F., Codjia, R., Galinier, M., Tourikis, P., Stavroula, M., Tousoulis, D., Stefanadis, C., Chrysohoou, C., Kotrogiannis, I., Matzaraki, V., Dimitroula, T., Karavidas, A., Tsitsinakis, G., Kapelios, C., Nanas, J., Kampouri, H., Nana, E., Kaldara, E., Eugenidou, A., Vardas, P., Saloustros, I., Patrianakos, A., Tsaknakis, T., Evangelou, S., Nikoloulis, N., Tziourganou, H., Tsaroucha, A., Papadopoulou, A., Douras, A., Polgar, L., Merkely, B., Kosztin, A., Nyolczas, N., Nagy, A. C., Halmosi, R., Elber, J., Alony, I., Shotan, A., Fuhrmann, A. V., Amir, O., Romano, S., Marcon, S., Penco, M., Di Mauro, M., Lemme, E., Carubelli, V., Rovetta, R., Metra, M., Bulgari, M., Quinzani, F., Lombardi, C., Bosi, S., Schiavina, G., Squeri, A., Barbieri, A., Di Tano, G., Pirelli, S., Ferrari, R., Fucili, A., Passero, T., Musio, S., Di Biase, M., Correale, M., Salvemini, G., Brognoli, S., Zanelli, E., Giordano, A., Agostoni, P., Italiano, G., Salvioni, E., Copelli, S., Modena, M. G., Reggianini, L., Valenti, C., Olaru, A., Bandino, S., Deidda, M., Mercuro, G., Dessalvi, C. C., Marino, P. N., Di Ruocco, M. V., Sartori, C., Piccinino, C., Parrinello, G., Licata, G., Torres, D., Giambanco, S., Busalacchi, S., Arrotti, S., Novo, S., Inciardi, R. M., Pieri, P., Chirco, P. R., Galifi, M. A., Teresi, G., Buccheri, D., Minacapelli, A., Veniani, M., Frisinghelli, A., Priori, S. G., Cattaneo, S., Opasich, C., Gualco, A., Pagliaro, M., Mancone, M., Fedele, F., Cinque, A., Vellini, M., Scarfo, I., Romeo, F., Ferraiuolo, F., Sergi, D., Anselmi, M., Melandri, F., Leci, E., Iori, E., Bovolo, V., Pidello, S., Frea, S., Bergerone, S., Botta, M., Canavosio, F. G., Gaita, F., Merlo, M., Cinquetti, M., Sinagra, G., Ramani, F., Fabris, E., Stolfo, D., Artico, J., Miani, D., Fresco, C., Daneluzzi, C., Proclemer, A., Cicoira, M., Zanolla, L., Marchese, G., Torelli, F., Vassanelli, C., Voronina, N., Erglis, A., Tamakauskas, V., Smalinskas, V., Karaliute, R., Petraskiene, I., Kazakauskaite, E., Rumbinaite, E., Kavoliuniene, A., Vysniauskas, V., Brazyte-Ramanauskiene, R., Petraskiene, D., Stankala, S., Switala, P., Juszczyk, Z., Sinkiewicz, W., Gilewski, W., Pietrzak, J., Orzel, T., Kasztelowicz, P., Kardaszewicz, P., Lazorko-Piega, M., Gabryel, J., Mosakowska, K., Bellwon, J., Rynkiewicz, A., Raczak, G., Lewicka, E., Dabrowska-Kugacka, A., Bartkowiak, R., Sosnowska-Pasiarska, B., Wozakowska-Kaplon, B., Krzeminski, A., Zabojszcz, M., Mirek-Bryniarska, E., Grzegorzko, A., Bury, K., Nessler, J., Zalewski, J., Furman, A., Broncel, M., Poliwczak, A., Bala, A., Zycinski, P., Rudzinska, M., Jankowski, L., Kasprzak, J. D., Michalak, L., Soska, K. W., Drozdz, J., Huziuk, I., Retwinski, A., Flis, P., Weglarz, J., Bodys, A., Grajek, S., Kaluzna-Oleksy, M., Straburzynska-Migaj, E., Dankowski, R., Szymanowska, K., Grabia, J., Szyszka, A., Nowicka, A., Samcik, M., Wolniewicz, L., Baczynska, K., Komorowska, K., Poprawa, I., Komorowska, E., Sajnaga, D., Zolbach, A., Dudzik-Plocica, A., Abdulkarim, A. -F., Lauko-Rachocka, A., Kaminski, L., Kostka, A., Cichy, A., Ruszkowski, P., Splawski, M., Fitas, G., Szymczyk, A., Serwicka, A., Fiega, A., Zysko, D., Krysiak, W., Szabowski, S., Skorek, E., Pruszczyk, P., Bienias, P., Ciurzynski, M., Welnicki, M., Mamcarz, A., Folga, A., Zielinski, T., Rywik, T., Leszek, P., Sobieszczanska-Malek, M., Piotrowska, M., Kozar-Kaminska, K., Komuda, K., Wisniewska, J., Tarnowska, A., Balsam, P., Marchel, M., Opolski, G., Kaplon-Cieslicka, A., Gil, R. J., Mozenska, O., Byczkowska, K., Gil, K., Pawlak, A., Michalek, A., Krzesinski, P., Piotrowicz, K., Uzieblo-Zyczkowska, B., Stanczyk, A., Skrobowski, A., Jankowska, E., Rozentryt, P., Polonski, L., Gadula-Gacek, E., Nowalany-Kozielska, E., Kuczaj, A., Kalarus, Z., Szulik, M., Przybylska, K., Klys, J., Prokop-Lewicka, G., Kleinrok, A., Aguiar, C. T., Ventosa, A., Pereira, S., Faria, R., Chin, J., De Jesus, I., Santos, R., Silva, P., Moreno, N., Queiros, C., Lourenco, C., Pereira, A., Castro, A., Andrade, A., Guimaraes, T. O., Martins, S., Placido, R., Lima, G., Brito, D., Francisco, A. R., Cardiga, R., Proenca, M., Araujo, I., Marques, F., Fonseca, C., Moura, B., Leite, S., Campelo, M., Silva-Cardoso, J., Rodrigues, J., Rangel, I., Martins, E., Correia, A. S., Peres, M., Marta, L., da Silva, G. F., Severino, D., Durao, D., Leao, S., Magalhaes, P., Moreira, I., Cordeiro, A. F., Ferreira, C., Araujo, C., Ferreira, A., Baptista, A., Radoi, M., Bicescu, G., Vinereanu, D., Sinescu, C. -J., Macarie, C., Popescu, R., Daha, I., Dan, G. -A., Stanescu, C., Dan, A., Craiu, E., Nechita, E., Aursulesei, V., Christodorescu, R., Otasevic, P., Seferovic, P. M., Simeunovic, D., Ristic, A. D., Celic, V., Pavlovic-Kleut, M., Lazic, J. S., Stojcevski, B., Pencic, B., Stevanovic, A., Andric, A., Iric-Cupic, V., Jovic, M., Davidovic, G., Milanov, S., Mitic, V., Atanaskovic, V., Antic, S., Pavlovic, M., Stanojevic, D., Stoickov, V., Ilic, S., Ilic, M. D., Petrovic, D., Stojsic, S., Kecojevic, S., Dodic, S., Adic, N. C., Cankovic, M., Stojiljkovic, J., Mihajlovic, B., Radin, A., Radovanovic, S., Krotin, M., Klabnik, A., Goncalvesova, E., Pernicky, M., Murin, J., Kovar, F., Kmec, J., Semjanova, H., Strasek, M., Iskra, M. S., Ravnikar, T., Suligoj, N. C., Komel, J., Fras, Z., Jug, B., Glavic, T., Losic, R., Bombek, M., Krajnc, I., Krunic, B., Horvat, S., Kovac, D., Rajtman, D., Cencic, V., Letonja, M., Winkler, R., Valentincic, M., Melihen-Bartolic, C., Bartolic, A., Vrckovnik, M. P., Kladnik, M., Pusnik, C. S., Marolt, A., Klen, J., Drnovsek, B., Leskovar, B., Anguita, M. J. F., Page, J. C. G., Martinez, F. M. S., Andres, J., Bayes-Genis, A., Mirabet, S., Mendez, A., Garcia-Cosio, L., Roig, E., Leon, V., Gonzalez-Costello, J., Muntane, G., Garay, A., Alcade-Martinez, V., Fernandez, S. L., Rivera-Lopez, R., Puga-Martinez, M., Fernandez-Alvarez, M., Serrano-Martinez, J. L., Crespo-Leiro, M., Grille-Cancela, Z., Marzoa-Rivas, R., Blanco-Canosa, P., Paniagua-Martin, M. J., Barge-Caballero, E., Cerdena, I. L., Baldomero, I. F. H., Padron, A. L., Rosillo, S. O., Gonzalez-Gallarza, R. D., Montanes, O. S., Manjavacas, A. M. I., Conde, A. C., Araujo, A., Soria, T., Garcia-Pavia, P., Gomez-Bueno, M., Cobo-Marcos, M., Alonso-Pulpon, L., Cubero, J. S., Sayago, I., Gonzalez-Segovia, A., Briceno, A., Subias, P. E., Hernandez, M. V., Cano, M. J. R., Sanchez, M. A. G., Jimenez, J. F. D., Garrido-Lestache, E. B., Pinilla, J. M. G., de la Villa, B. G., Sahuquillo, A., Marques, R. B., Calvo, F. T., Perez-Martinez, M. T., Gracia-Rodenas, M. R., Garrido-Bravo, I. P., Pastor-Perez, F., Pascual-Figal, D. A., Molina, B. D., Orus, J., Gonzalo, F. E., Bertomeu, V., Valero, R., Martinez-Abellan, R., Quiles, J., Rodrigez-Ortega, J. A., Mateo, I., Elamrani, A., Fernandez-Vivancos, C., Valero, D. B., Almenar-Bonet, L., Sanchez-Lazaro, I. J., Marques-Sule, E., Facila-Rubio, L., Perez-Silvestre, J., Garcia-Gonzalez, P., Ridocci-Soriano, F., Garcia-Escriva, D., Pellicer-Cabo, A., de la Fuente Galan, L., Diaz, J. L., Platero, A. R., Arias, J. C., Blasco-Peiro, T., Julve, M. S., Sanchez-Insa, E., Aured-Guallar, C., Portoles-Ocampo, A., Melin, M., Hagglund, E., Stenberg, A., Lindahl, I. -M., Asserlund, B., Olsson, L., Dahlstrom, U., Afzelius, M., Karlstrom, P., Tengvall, L., Wiklund, P. -A., Olsson, B., Kalayci, S., Temizhan, A., Cavusoglu, Y., Gencer, E., Yilmaz, M. B., and Gunes, H.
Subjects: Adult, Male, Registry, medicine.medical_specialty, New York Heart Association Class, Acute heart failure, Congestion, Forrester classification, Outcomes, Perfusion, Acute Disease, Aged, Blood Pressure, Coronary Circulation, Female, Follow-Up Studies, Heart Failure, Hospital Mortality, Humans, Long-Term Care, Middle Aged, Registries, Risk Factors, Treatment Outcome, Hospitalization, 030204 cardiovascular system & hematology, Lower risk, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, Long term outcomes, Medicine, Outcome, business.industry, Hazard ratio, acute heart failure, congestion, forrester classification, outcomes, perfusion, registry, acute disease, adult, aged, blood pressure, coronary circulation, female, follow-up studies, heart failure, hospital mortality, humans, long-term care, male, middle aged, registries, risk factors, treatment outcome, hospitalization, medicine.disease, Confidence interval, 3. Good health, Heart failure, Emergency medicine, Cardiology and Cardiovascular Medicine, business
Abstract: [Abstract] Aims: Classification of acute heart failure (AHF) patients into four clinical profiles defined by evidence of congestion and perfusion is advocated by the 2016 European Society of Cardiology (ESC)guidelines. Based on the ESC-EORP-HFA Heart Failure Long-Term Registry, we compared differences in baseline characteristics, in-hospital management and outcomes among congestion/perfusion profiles using this classification. Methods and results: We included 7865 AHF patients classified at admission as: 'dry-warm' (9.9%), 'wet-warm' (69.9%), 'wet-cold' (19.8%) and 'dry-cold' (0.4%). These groups differed significantly in terms of baseline characteristics, in-hospital management and outcomes. In-hospital mortality was 2.0% in 'dry-warm', 3.8% in 'wet-warm', 9.1% in 'dry-cold' and 12.1% in 'wet-cold' patients. Based on clinical classification at admission, the adjusted hazard ratios (95% confidence interval) for 1-year mortality were: 'wet-warm' vs. 'dry-warm' 1.78 (1.43-2.21) and 'wet-cold' vs. 'wet-warm' 1.33 (1.19-1.48). For profiles resulting from discharge classification, the adjusted hazard ratios (95% confidence interval) for 1-year mortality were: 'wet-warm' vs. 'dry-warm' 1.46 (1.31-1.63) and 'wet-cold' vs. 'wet-warm' 2.20 (1.89-2.56). Among patients discharged alive, 30.9% had residual congestion, and these patients had higher 1-year mortality compared to patients discharged without congestion (28.0 vs. 18.5%). Tricuspid regurgitation, diabetes, anaemia and high New York Heart Association class were independently associated with higher risk of congestion at discharge, while beta-blockers at admission, de novo heart failure, or any cardiovascular procedure during hospitalization were associated with lower risk of residual congestion. Conclusion: Classification based on congestion/perfusion status provides clinically relevant information at hospital admission and discharge. A better understanding of the clinical course of the two entities could play an important role towards the implementation of targeted strategies that may improve outcomes.
Published: 2019

8. Sacubitril/valsartan eligibility and outcomes in the ESC-EORP-HFA Heart Failure Long-Term Registry: bridging between European Medicines Agency/Food and Drug Administration label, the PARADIGM-HF trial, ESC guidelines, and real world

Author: Kapelios C. J., Lainscak M., Savarese G., Laroche C., Seferovic P., Ruschitzka F., Coats A., Anker S. D., Crespo-Leiro M. G., Filippatos G., Piepoli M. F., Rosano G., Zanolla L., Aguiar C., Murin J., Leszek P., McDonagh T., Maggioni A. P., Lund L. H., Auer J., Ablasser K., Fruhwald F., Dolze T., Brandner K., Gstrein S., Poelzl G., Moertl D., Reiter S., Podczeck-Schweighofer A., Muslibegovic A., Vasilj M., Fazlibegovic E., Cesko M., Zelenika D., Palic B., Pravdic D., Cuk D., Vitlianova K., Katova T., Velikov T., Kurteva T., Gatzov P., Kamenova D., Antova M., Sirakova V., Krejci J., Mikolaskova M., Spinar J., Krupicka J., Malek F., Hegarova M., Lazarova M., Monhart Z., Hassanein M., Sobhy M., El Messiry F., El Shazly A. H., Elrakshy Y., Youssef A., Moneim A. A., Noamany M., Reda A., Abdel Dayem T. K., Farag N., Ibrahim Halawa S., Abdel Hamid M., Said K., Saleh A., Ebeid H., Hanna R., Aziz R., Louis O., Enen M. A., Ibrahim B. S., Nasr G., Elbahry A., Sobhy H., Ashmawy M., Gouda M., Aboleineen W., Bernard Y., Luporsi P., Meneveau N., Pillot M., Morel M., Seronde M. -F., Schiele F., Briand F., Delahaye F., Damy T., Eicher J. -C., de Groote P., Fertin M., Lamblin N., Isnard R., Lefol C., Thevenin S., Hagege A., Jondeau G., Logeart D., Le Marcis V., Ly J. -F., Coisne D., Lequeux B., Le Moal V., Mascle S., Lotton P., Behar N., Donal E., Thebault C., Ridard C., Reynaud A., Basquin A., Bauer F., Codjia R., Galinier M., Tourikis P., Stavroula M., Tousoulis D., Stefanadis C., Chrysohoou C., Kotrogiannis I., Matzaraki V., Dimitroula T., Karavidas A., Tsitsinakis G., Kapelios C., Nanas J., Kampouri H., Nana E., Kaldara E., Eugenidou A., Vardas P., Saloustros I., Patrianakos A., Tsaknakis T., Evangelou S., Nikoloulis N., Tziourganou H., Tsaroucha A., Papadopoulou A., Douras A., Polgar L., Merkely B., Kosztin A., Nyolczas N., Csaba Nagy A., Halmosi R., Elber J., Alony I., Shotan A., Vazan Fuhrmann A., Amir O., Romano S., Marcon S., Penco M., Di Mauro M., Lemme E., Carubelli V., Rovetta R., Metra M., Bulgari M., Quinzani F., Lombardi C., Bosi S., Schiavina G., Squeri A., Barbieri A., Di Tano G., Pirelli S., Ferrari R., Fucili A., Passero T., Musio S., Di Biase M., Correale M., Salvemini G., Brognoli S., Zanelli E., Giordano A., Agostoni P., Italiano G., Salvioni E., Copelli S., Modena M. G., Reggianini L., Valenti C., Olaru A., Bandino S., Deidda M., Mercuro G., Cadeddu Dessalvi C., Marino P. N., Di Ruocco M. V., Sartori C., Piccinino C., Parrinello G., Licata G., Torres D., Giambanco S., Busalacchi S., Arrotti S., Novo S., Inciardi R. M., Pieri P., Chirco P. R., Ausilia Galifi M., Teresi G., Buccheri D., Minacapelli A., Veniani M., Frisinghelli A., Priori S. G., Cattaneo S., Opasich C., Gualco A., Pagliaro M., Mancone M., Fedele F., Cinque A., Vellini M., Scarfo I., Romeo F., Ferraiuolo F., Sergi D., Anselmi M., Melandri F., Leci E., Iori E., Bovolo V., Pidello S., Frea S., Bergerone S., Botta M., Canavosio F. G., Gaita F., Merlo M., Cinquetti M., Sinagra G., Ramani F., Fabris E., Stolfo D., Artico J., Miani D., Fresco C., Daneluzzi C., Proclemer A., Cicoira M., Marchese G., Torelli F., Vassanelli C., Voronina N., Erglis A., Tamakauskas V., Smalinskas V., Karaliute R., Petraskiene I., Kazakauskaite E., Rumbinaite E., Kavoliuniene A., Vysniauskas V., Brazyte-Ramanauskiene R., Petraskiene D., Stankala S., Switala P., Juszczyk Z., Sinkiewicz W., Gilewski W., Pietrzak J., Orzel T., Kasztelowicz P., Kardaszewicz P., Lazorko-Piega M., Gabryel J., Mosakowska K., Bellwon J., Rynkiewicz A., Raczak G., Lewicka E., Dabrowska-Kugacka A., Bartkowiak R., Sosnowska-Pasiarska B., Wozakowska-Kaplon B., Krzeminski A., Zabojszcz M., Mirek-Bryniarska E., Grzegorzko A., Bury K., Nessler J., Zalewski J., Furman A., Broncel M., Poliwczak A., Bala A., Zycinski P., Rudzinska M., Jankowski L., Kasprzak J. D., Michalak L., Wojtczak Soska K., Drozdz J., Huziuk I., Retwinski A., Flis P., Weglarz J., Bodys A., Grajek S., Kaluzna-Oleksy M., Straburzynska-Migaj E., Dankowski R., Szymanowska K., Grabia J., Szyszka A., Nowicka A., Samcik M., Wolniewicz L., Baczynska K., Komorowska K., Poprawa I., Komorowska E., Sajnaga D., Zolbach A., Dudzik-Plocica A., Abdulkarim A. -F., Lauko-Rachocka A., Kaminski L., Kostka A., Cichy A., Ruszkowski P., Splawski M., Fitas G., Szymczyk A., Serwicka A., Fiega A., Zysko D., Krysiak W., Szabowski S., Skorek E., Pruszczyk P., Bienias P., Ciurzynski M., Welnicki M., Mamcarz A., Folga A., Zielinski T., Rywik T., Sobieszczanska-Malek M., Piotrowska M., Kozar-Kaminska K., Komuda K., Wisniewska J., Tarnowska A., Balsam P., Marchel M., Opolski G., Kaplon-Cieslicka A., Gil R. J., Mozenska O., Byczkowska K., Gil K., Pawlak A., Michalek A., Krzesinski P., Piotrowicz K., Uzieblo-Zyczkowska B., Stanczyk A., Skrobowski A., Ponikowski P., Jankowska E., Rozentryt P., Polonski L., Gadula-Gacek E., Nowalany-Kozielska E., Kuczaj A., Kalarus Z., Szulik M., Przybylska K., Klys J., Prokop-Lewicka G., Kleinrok A., Tavares Aguiar C., Ventosa A., Pereira S., Faria R., Chin J., De Jesus I., Santos R., Silva P., Moreno N., Queiros C., Lourenco C., Pereira A., Castro A., Andrade A., Oliveira Guimaraes T., Martins S., Placido R., Lima G., Brito D., Francisco A. R., Cardiga R., Proenca M., Araujo I., Marques F., Fonseca C., Moura B., Leite S., Campelo M., Silva-Cardoso J., Rodrigues J., Rangel I., Martins E., Sofia Correia A., Peres M., Marta L., Ferreira da Silva G., Severino D., Durao D., Leao S., Magalhaes P., Moreira I., Filipa Cordeiro A., Ferreira C., Araujo C., Ferreira A., Baptista A., Radoi M., Bicescu G., Vinereanu D., Sinescu C. -J., Macarie C., Popescu R., Daha I., Dan G. -A., Stanescu C., Dan A., Craiu E., Nechita E., Aursulesei V., Christodorescu R., Otasevic P., Seferovic P. M., Simeunovic D., Ristic A. 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S., Nasr, G., Elbahry, A., Sobhy, H., Ashmawy, M., Gouda, M., Aboleineen, W., Bernard, Y., Luporsi, P., Meneveau, N., Pillot, M., Morel, M., Seronde, M. -F., Schiele, F., Briand, F., Delahaye, F., Damy, T., Eicher, J. -C., de Groote, P., Fertin, M., Lamblin, N., Isnard, R., Lefol, C., Thevenin, S., Hagege, A., Jondeau, G., Logeart, D., Le Marcis, V., Ly, J. -F., Coisne, D., Lequeux, B., Le Moal, V., Mascle, S., Lotton, P., Behar, N., Donal, E., Thebault, C., Ridard, C., Reynaud, A., Basquin, A., Bauer, F., Codjia, R., Galinier, M., Tourikis, P., Stavroula, M., Tousoulis, D., Stefanadis, C., Chrysohoou, C., Kotrogiannis, I., Matzaraki, V., Dimitroula, T., Karavidas, A., Tsitsinakis, G., Kapelios, C., Nanas, J., Kampouri, H., Nana, E., Kaldara, E., Eugenidou, A., Vardas, P., Saloustros, I., Patrianakos, A., Tsaknakis, T., Evangelou, S., Nikoloulis, N., Tziourganou, H., Tsaroucha, A., Papadopoulou, A., Douras, A., Polgar, L., Merkely, B., Kosztin, A., Nyolczas, N., Csaba Nagy, A., Halmosi, R., Elber, J., Alony, I., Shotan, A., Vazan Fuhrmann, A., Amir, O., Romano, S., Marcon, S., Penco, M., Di Mauro, M., Lemme, E., Carubelli, V., Rovetta, R., Metra, M., Bulgari, M., Quinzani, F., Lombardi, C., Bosi, S., Schiavina, G., Squeri, A., Barbieri, A., Di Tano, G., Pirelli, S., Ferrari, R., Fucili, A., Passero, T., Musio, S., Di Biase, M., Correale, M., Salvemini, G., Brognoli, S., Zanelli, E., Giordano, A., Agostoni, P., Italiano, G., Salvioni, E., Copelli, S., Modena, M. G., Reggianini, L., Valenti, C., Olaru, A., Bandino, S., Deidda, M., Mercuro, G., Cadeddu Dessalvi, C., Marino, P. N., Di Ruocco, M. V., Sartori, C., Piccinino, C., Parrinello, G., Licata, G., Torres, D., Giambanco, S., Busalacchi, S., Arrotti, S., Novo, S., Inciardi, R. M., Pieri, P., Chirco, P. R., Ausilia Galifi, M., Teresi, G., Buccheri, D., Minacapelli, A., Veniani, M., Frisinghelli, A., Priori, S. G., Cattaneo, S., Opasich, C., Gualco, A., Pagliaro, M., Mancone, M., Fedele, F., Cinque, A., Vellini, M., Scarfo, I., Romeo, F., Ferraiuolo, F., Sergi, D., Anselmi, M., Melandri, F., Leci, E., Iori, E., Bovolo, V., Pidello, S., Frea, S., Bergerone, S., Botta, M., Canavosio, F. G., Gaita, F., Merlo, M., Cinquetti, M., Sinagra, G., Ramani, F., Fabris, E., Stolfo, D., Artico, J., Miani, D., Fresco, C., Daneluzzi, C., Proclemer, A., Cicoira, M., Marchese, G., Torelli, F., Vassanelli, C., Voronina, N., Erglis, A., Tamakauskas, V., Smalinskas, V., Karaliute, R., Petraskiene, I., Kazakauskaite, E., Rumbinaite, E., Kavoliuniene, A., Vysniauskas, V., Brazyte-Ramanauskiene, R., Petraskiene, D., Stankala, S., Switala, P., Juszczyk, Z., Sinkiewicz, W., Gilewski, W., Pietrzak, J., Orzel, T., Kasztelowicz, P., Kardaszewicz, P., Lazorko-Piega, M., Gabryel, J., Mosakowska, K., Bellwon, J., Rynkiewicz, A., Raczak, G., Lewicka, E., Dabrowska-Kugacka, A., Bartkowiak, R., Sosnowska-Pasiarska, B., Wozakowska-Kaplon, B., Krzeminski, A., Zabojszcz, M., Mirek-Bryniarska, E., Grzegorzko, A., Bury, K., Nessler, J., Zalewski, J., Furman, A., Broncel, M., Poliwczak, A., Bala, A., Zycinski, P., Rudzinska, M., Jankowski, L., Kasprzak, J. D., Michalak, L., Wojtczak Soska, K., Drozdz, J., Huziuk, I., Retwinski, A., Flis, P., Weglarz, J., Bodys, A., Grajek, S., Kaluzna-Oleksy, M., Straburzynska-Migaj, E., Dankowski, R., Szymanowska, K., Grabia, J., Szyszka, A., Nowicka, A., Samcik, M., Wolniewicz, L., Baczynska, K., Komorowska, K., Poprawa, I., Komorowska, E., Sajnaga, D., Zolbach, A., Dudzik-Plocica, A., Abdulkarim, A. -F., Lauko-Rachocka, A., Kaminski, L., Kostka, A., Cichy, A., Ruszkowski, P., Splawski, M., Fitas, G., Szymczyk, A., Serwicka, A., Fiega, A., Zysko, D., Krysiak, W., Szabowski, S., Skorek, E., Pruszczyk, P., Bienias, P., Ciurzynski, M., Welnicki, M., Mamcarz, A., Folga, A., Zielinski, T., Rywik, T., Sobieszczanska-Malek, M., Piotrowska, M., Kozar-Kaminska, K., Komuda, K., Wisniewska, J., Tarnowska, A., Balsam, P., Marchel, M., Opolski, G., Kaplon-Cieslicka, A., Gil, R. J., Mozenska, O., Byczkowska, K., Gil, K., Pawlak, A., Michalek, A., Krzesinski, P., Piotrowicz, K., Uzieblo-Zyczkowska, B., Stanczyk, A., Skrobowski, A., Ponikowski, P., Jankowska, E., Rozentryt, P., Polonski, L., Gadula-Gacek, E., Nowalany-Kozielska, E., Kuczaj, A., Kalarus, Z., Szulik, M., Przybylska, K., Klys, J., Prokop-Lewicka, G., Kleinrok, A., Tavares Aguiar, C., Ventosa, A., Pereira, S., Faria, R., Chin, J., De Jesus, I., Santos, R., Silva, P., Moreno, N., Queiros, C., Lourenco, C., Pereira, A., Castro, A., Andrade, A., Oliveira Guimaraes, T., Martins, S., Placido, R., Lima, G., Brito, D., Francisco, A. R., Cardiga, R., Proenca, M., Araujo, I., Marques, F., Fonseca, C., Moura, B., Leite, S., Campelo, M., Silva-Cardoso, J., Rodrigues, J., Rangel, I., Martins, E., Sofia Correia, A., Peres, M., Marta, L., Ferreira da Silva, G., Severino, D., Durao, D., Leao, S., Magalhaes, P., Moreira, I., Filipa Cordeiro, A., Ferreira, C., Araujo, C., Ferreira, A., Baptista, A., Radoi, M., Bicescu, G., Vinereanu, D., Sinescu, C. -J., Macarie, C., Popescu, R., Daha, I., Dan, G. -A., Stanescu, C., Dan, A., Craiu, E., Nechita, E., Aursulesei, V., Christodorescu, R., Otasevic, P., Seferovic, P. M., Simeunovic, D., Ristic, A. D., Celic, V., Pavlovic-Kleut, M., Suzic Lazic, J., Stojcevski, B., Pencic, B., Stevanovic, A., Andric, A., Iric-Cupic, V., Jovic, M., Davidovic, G., Milanov, S., Mitic, V., Atanaskovic, V., Antic, S., Pavlovic, M., Stanojevic, D., Stoickov, V., Ilic, S., Deljanin Ilic, M., Petrovic, D., Stojsic, S., Kecojevic, S., Dodic, S., Cemerlic Adic, N., Cankovic, M., Stojiljkovic, J., Mihajlovic, B., Radin, A., Radovanovic, S., Krotin, M., Klabnik, A., Goncalvesova, E., Pernicky, M., Kovar, F., Kmec, J., Semjanova, H., Strasek, M., Savnik Iskra, M., Ravnikar, T., Cernic Suligoj, N., Komel, J., Fras, Z., Jug, B., Glavic, T., Losic, R., Bombek, M., Krajnc, I., Krunic, B., Horvat, S., Kovac, D., Rajtman, D., Cencic, V., Letonja, M., Winkler, R., Valentincic, M., Melihen-Bartolic, C., Bartolic, A., Pusnik Vrckovnik, M., Kladnik, M., Slemenik Pusnik, C., Marolt, A., Klen, J., Drnovsek, B., Leskovar, B., Fernandez Anguita, M. J., Gallego Page, J. C., Salmeron Martinez, F. M., Andres, J., Bayes-Genis, A., Mirabet, S., Mendez, A., Garcia-Cosio, L., Roig, E., Leon, V., Gonzalez-Costello, J., Muntane, G., Garay, A., Alcade-Martinez, V., Lopez Fernandez, S., Rivera-Lopez, R., Puga-Martinez, M., Fernandez-Alvarez, M., Serrano-Martinez, J. L., Crespo-Leiro, M., Grille-Cancela, Z., Marzoa-Rivas, R., Blanco-Canosa, P., Paniagua-Martin, M. J., Barge-Caballero, E., Laynez Cerdena, I., Famara Hernandez Baldomero, I., Lara Padron, A., Ofelia Rosillo, S., Dalmau Gonzalez-Gallarza, R., Salvador Montanes, O., Iniesta Manjavacas, A. M., Castro Conde, A., Araujo, A., Soria, T., Garcia-Pavia, P., Gomez-Bueno, M., Cobo-Marcos, M., Alonso-Pulpon, L., Segovia Cubero, J., Sayago, I., Gonzalez-Segovia, A., Briceno, A., Escribano Subias, P., Vicente Hernandez, M., Ruiz Cano, M. J., Gomez Sanchez, M. A., Delgado Jimenez, J. F., Barrios Garrido-Lestache, E., Garcia Pinilla, J. M., Garcia de la Villa, B., Sahuquillo, A., Bravo Marques, R., Torres Calvo, F., Perez-Martinez, M. T., Gracia-Rodenas, M. R., Garrido-Bravo, I. P., Pastor-Perez, F., Pascual-Figal, D. A., Diaz Molina, B., Orus, J., Epelde Gonzalo, F., Bertomeu, V., Valero, R., Martinez-Abellan, R., Quiles, J., Rodrigez-Ortega, J. A., Mateo, I., Elamrani, A., Fernandez-Vivancos, C., Bierge Valero, D., Almenar-Bonet, L., Sanchez-Lazaro, I. J., Marques-Sule, E., Facila-Rubio, L., Perez-Silvestre, J., Garcia-Gonzalez, P., Ridocci-Soriano, F., Garcia-Escriva, D., Pellicer-Cabo, A., de la Fuente Galan, L., Lopez Diaz, J., Recio Platero, A., Arias, J. C., Blasco-Peiro, T., Sanz Julve, M., Sanchez-Insa, E., Aured-Guallar, C., Portoles-Ocampo, A., Melin, M., Hagglund, E., Stenberg, A., Lindahl, I. -M., Asserlund, B., Olsson, L., Dahlstrom, U., Afzelius, M., Karlstrom, P., Tengvall, L., Wiklund, P. -A., Olsson, B., Kalayci, S., Temizhan, A., Cavusoglu, Y., Gencer, E., Yilmaz, M. B., and Gunes, H.
Subjects: medicine.medical_specialty, Registry, Prognosi, Tetrazoles, 030204 cardiovascular system & hematology, Angiotensin receptor, Sacubitril, 03 medical and health sciences, Angiotensin Receptor Antagonists, 0302 clinical medicine, Internal medicine, medicine, neprilysin inhibitor, Humans, LCZ696, Enalapril, Registries, Sacubitril/valsartan, New York Heart Association Class I, Heart Failure, Angiotensin receptor–neprilysin inhibitor, Eligibility, Ejection fraction, business.industry, United States Food and Drug Administration, Aminobutyrates, Biphenyl Compounds, Stroke Volume, Guideline, Prognosis, Neprilysin, United States, Valsartan, medicine.disease, 3. Good health, Drug Combinations, Heart failure, Cardiology and Cardiovascular Medicine, business, angiotensin receptor–neprilysin inhibitor, eligibility, lcz696, prognosis, registry, sacubitril/valsartan, aminobutyrates, angiotensin receptor antagonists, humans, neprilysin, registries, stroke volume, tetrazoles, united states, united states food and drug administration, valsartan, heart failure, Sacubitril, Valsartan, medicine.drug
Abstract: Aims To assess the proportion of patients with heart failure and reduced ejection fraction (HFrEF) who are eligible for sacubitril/valsartan (LCZ696) based on the European Medicines Agency/Food and Drug Administration (EMA/FDA) label, the PARADIGM-HF trial and the 2016 ESC guidelines, and the association between eligibility and outcomes. Methods and results Outpatients with HFrEF in the ESC-EORP-HFA Long-Term Heart Failure (HF-LT) Registry between March 2011 and November 2013 were considered. Criteria for LCZ696 based on EMA/FDA label, PARADIGM-HF and ESC guidelines were applied. Of 5443 patients, 2197 and 2373 had complete information for trial and guideline eligibility assessment, and 84%, 12% and 12% met EMA/FDA label, PARADIGM-HF and guideline criteria, respectively. Absent PARADIGM-HF criteria were low natriuretic peptides (21%), hyperkalemia (4%), hypotension (7%) and sub-optimal pharmacotherapy (74%); absent Guidelines criteria were LVEF>35% (23%), insufficient NP levels (30%) and sub-optimal pharmacotherapy (82%); absent label criteria were absence of symptoms (New York Heart Association class I). When a daily requirement of ACEi/ARB >= 10mg enalapril (instead of >= 20 mg) was used, eligibility rose from 12% to 28% based on both PARADIGM-HF and guidelines. One-year heart failure hospitalization was higher (12% and 17% vs. 12%) and all-cause mortality lower (5.3% and 6.5% vs. 7.7%) in registry eligible patients compared to the enalapril arm of PARADIGM-HF. Conclusions Among outpatients with HFrEF in the ESC-EORP-HFA HF-LT Registry, 84% met label criteria, while only 12% and 28% met PARADIGM-HF and guideline criteria for LCZ696 if requiring >= 20 mg and >= 10mg enalapril, respectively. Registry patients eligible for LCZ696 had greater heart failure hospitalization but lower mortality rates than the PARADIGM-HF enalapril group.
Published: 2019

9. Sex- and age-related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long-Term Registry

Author: Lainšcak, M. Milinkovic, I. Polovina, M. Crespo-Leiro, M.G. Lund, L.H. Anker, S.D. Laroche, C. Ferrari, R. Coats, A.J.S. McDonagh, T. Filippatos, G. Maggioni, A.P. Piepoli, M.F. Rosano, G.M.C. Ruschitzka, F. Simic, D. Ašanin, M. Eicher, J.-C. Yilmaz, M.B. Seferovic, P.M. Gale, C.P. Chair, G.B. Branko Beleslin, R.S. Andrzej Budaj, P.L. Chioncel, R.O. Nikolaos Dagres, D.E. Nicolas Danchin, F.R. David Erlinge, S.E. Jonathan Emberson, G.B. Michael Glikson, I.L. Alastair Gray, G.B. Meral Kayikcioglu, T.R. Aldo Maggioni, I.T. Klaudia Vivien Nagy, H.U. Aleksandr Nedoshivin, R.U. Anna-Sonia Petronio, I.T. Jolien Roos-Hesselink, N.L. Lars Wallentin, S.E. Uwe Zeymer, D.E. Mebazaa, A. Coats, A. A. Goda, A.L. M. Diez, A.R. A. Fernandez, A.R. F. Fruhwald, A.T. Fazlibegovic, E. P. Gatzov, B.G. A. Kurlianskaya, B.Y. R. Hullin, C.H. T. Christodoulides, C.Y. J. Hradec, C.Z. O. Wendelboe Nielsen, D.K. R. Nedjar, D.Z. T. Uuetoa, E.E. M. Hassanein, E.G. J. F. Delgado Jimenez, E.S. V-P. Harjola, F.I. D. Logeart, F.R. V. Chumburidze, G.E. D. Tousoulis, G.R. D. Milicic, H.R. B. Merkely, H.U. O'Donoghue IE, E. O. Amir, I.L. A. Shotan, I.L. D. Shafie, I.R. M. Metra, I.T. A. Matsumori, J.P. E. Mirrakhimov, K.G. A. Kavoliuniene, L.T. A. Erglis, L.V. Vataman, E. M. Otljanska, M.K. E. Srbinovska Kostovska, M.K. D. Cassar DeMarco, M.T. J. Drozdz, P.L. Fonseca, C. M. Dekleva, R.S. E. Shkolnik, R.U. U. Dahlstrom, S.E. M. Lainscak, S.I. E. Goncalvesova, S.K. A. Temizhan, T.R. V. Estrago, U.Y. G. Bajraktari, X.K. Auer, J. Ablasser, K. Fruhwald, F. Dolze, T. Brandner, K. Gstrein, S. Poelzl, G. Moertl, D. Reiter, S. Podczeck-Schweighofer, A. Muslibegovic, A. Vasilj, M. Cesko, M. Zelenika, D. Palic, B. Pravdic, D. Cuk, D. Vitlianova, K. Katova, T. Velikov, T. Kurteva, T. Gatzov, P. Kamenova, D. Antova, M. Sirakova, V. Krejci, J. Mikolaskova, M. Spinar, J. Krupicka, J. Malek, F. Hegarova, M. Lazarova, M. Monhart, Z. Hassanein, M. Sobhy, M. El Messiry, F. El Shazly, A.H. Elrakshy, Y. Youssef, A. Moneim, A.A. Noamany, M. Reda, A. Dayem, T.K.A. Farag, N. Halawa, S.I. Hamid, M.A. Said, K. Saleh, A. Ebeid, H. Hanna, R. Aziz, R. Louis, O. Enen, M.A. Ibrahim, B.S. Nasr, G. Elbahry, A. Sobhy, H. Ashmawy, M. Gouda, M. Aboleineen, W. Bernard, Y. Luporsi, P. Meneveau, N. Pillot, M. Morel, M. Seronde, M.-F. Schiele, F. Briand, F. Delahaye, F. Damy, T. de Groote, P. Fertin, M. Lamblin, N. Isnard, R. Lefol, C. Thevenin, S. Hagege, A. Jondeau, G. Logeart, D. Le Marcis, V. Ly, J.-F. Coisne, D. Lequeux, B. Le Moal, V. Mascle, S. Lotton, P. Behar, N. Donal, E. Thebault, C. Ridard, C. Reynaud, A. Basquin, A. Bauer, F. Codjia, R. Galinier, M. Tourikis, P. Stavroula, M. Tousoulis, D. Stefanadis, C. Chrysohoou, C. Kotrogiannis, I. Matzaraki, V. Dimitroula, T. Karavidas, A. Tsitsinakis, G. Kapelios, C. Nanas, J. Kampouri, H. Nana, E. Kaldara, E. Eugenidou, A. Vardas, P. Saloustros, I. Patrianakos, A. Tsaknakis, T. Evangelou, S. Nikoloulis, N. Tziourganou, H. Tsaroucha, A. Papadopoulou, A. Douras, A. Polgar, L. Merkely, B. Kosztin, A. Nyolczas, N. Nagy, A.C. Halmosi, R. Elber, J. Alony, I. Shotan, A. Fuhrmann, A.V. Amir, O. Romano, S. Marcon, S. Penco, M. Di Mauro, M. Lemme, E. Carubelli, V. Rovetta, R. Metra, M. Bulgari, M. Quinzani, F. Lombardi, C. Bosi, S. Schiavina, G. Squeri, A. Barbieri, A. Di Tano, G. Pirelli, S. Fucili, A. Passero, T. Musio, S. Di Biase, M. Correale, M. Salvemini, G. Brognoli, S. Zanelli, E. Giordano, A. Agostoni, P. Italiano, G. Salvioni, E. Copelli, S. Modena, M.G. Reggianini, L. Valenti, C. Olaru, A. Bandino, S. Deidda, M. Mercuro, G. Dessalvi, C.C. Marino, P.N. Di Ruocco, M.V. Sartori, C. Piccinino, C. Parrinello, G. Licata, G. Torres, D. Giambanco, S. Busalacchi, S. Arrotti, S. Novo, S. Inciardi, R.M. Pieri, P. Chirco, P.R. Galifi, M.A. Teresi, G. Buccheri, D. Minacapelli, A. Veniani, M. Frisinghelli, A. Priori, S.G. Cattaneo, S. Opasich, C. Gualco, A. Pagliaro, M. Mancone, M. Fedele, F. Cinque, A. Vellini, M. Scarfo, I. Romeo, F. Ferraiuolo, F. Sergi, D. Anselmi, M. Melandri, F. Leci, E. Iori, E. Bovolo, V. Pidello, S. Frea, S. Bergerone, S. Botta, M. Canavosio, F.G. Gaita, F. Merlo, M. Cinquetti, M. Sinagra, G. Ramani, F. Fabris, E. Stolfo, D. Artico, J. Miani, D. Fresco, C. Daneluzzi, C. Proclemer, A. Cicoira, M. Zanolla, L. Marchese, G. Torelli, F. Vassanelli, C. Voronina, N. Erglis, A. Tamakauskas, V. Smalinskas, V. Karaliute, R. Petraskiene, I. Kazakauskaite, E. Rumbinaite, E. Kavoliuniene, A. Vysniauskas, V. Brazyte-Ramanauskiene, R. Petraskiene, D. Stankala, S. Switala, P. Juszczyk, Z. Sinkiewicz, W. Gilewski, W. Pietrzak, J. Orzel, T. Kasztelowicz, P. Kardaszewicz, P. Lazorko-Piega, M. Gabryel, J. Mosakowska, K. Bellwon, J. Rynkiewicz, A. Raczak, G. Lewicka, E. Dabrowska-Kugacka, A. Bartkowiak, R. Sosnowska-Pasiarska, B. Wozakowska-Kaplon, B. Krzeminski, A. Zabojszcz, M. Mirek-Bryniarska, E. Grzegorzko, A. Bury, K. Nessler, J. Zalewski, J. Furman, A. Broncel, M. Poliwczak, A. Bala, A. Zycinski, P. Rudzinska, M. Jankowski, L. Kasprzak, J.D. Michalak, L. Soska, K.W. Drozdz, J. Huziuk, I. Retwinski, A. Flis, P. Weglarz, J. Bodys, A. Grajek, S. Kaluzna-Oleksy, M. Straburzynska-Migaj, E. Dankowski, R. Szymanowska, K. Grabia, J. Szyszka, A. Nowicka, A. Samcik, M. Wolniewicz, L. Baczynska, K. Komorowska, K. Poprawa, I. Komorowska, E. Sajnaga, D. Zolbach, A. Dudzik-Plocica, A. Abdulkarim, A.-F. Lauko-Rachocka, A. Kaminski, L. Kostka, A. Cichy, A. Ruszkowski, P. Splawski, M. Fitas, G. Szymczyk, A. Serwicka, A. Fiega, A. Zysko, D. Krysiak, W. Szabowski, S. Skorek, E. Pruszczyk, P. Bienias, P. Ciurzynski, M. Welnicki, M. Mamcarz, A. Folga, A. Zielinski, T. Rywik, T. Leszek, P. Sobieszczanska-Malek, M. Piotrowska, M. Kozar-Kaminska, K. Komuda, K. Wisniewska, J. Tarnowska, A. Balsam, P. Marchel, M. Opolski, G. Kaplon-Cieslicka, A. Gil, R.J. Mozenska, O. Byczkowska, K. Gil, K. Pawlak, A. Michalek, A. Krzesinski, P. Piotrowicz, K. Uzieblo-Zyczkowska, B. Stanczyk, A. Skrobowski, A. Ponikowski, P. Jankowska, E. Rozentryt, P. Polonski, L. Gadula-Gacek, E. Nowalany-Kozielska, E. Kuczaj, A. Kalarus, Z. Szulik, M. Przybylska, K. Klys, J. Prokop-Lewicka, G. Kleinrok, A. Aguiar, C.T. Ventosa, A. Pereira, S. Faria, R. Chin, J. De Jesus, I. Santos, R. Silva, P. Moreno, N. Queirós, C. Lourenço, C. Pereira, A. Castro, A. Andrade, A. Guimaraes, T.O. Martins, S. Placido, R. Lima, G. Brito, D. Francisco, A.R. Cardiga, R. Proenca, M. Araujo, I. Marques, F. Moura, B. Leite, S. Campelo, M. Silva-Cardoso, J. Rodrigues, J. Rangel, I. Martins, E. Correia, A.S. Peres, M. Marta, L. da Silva, G.F. Severino, D. Durao, D. Leao, S. Magalhaes, P. Moreira, I. Cordeiro, A.F. Ferreira, C. Araujo, C. Ferreira, A. Baptista, A. Radoi, M. Bicescu, G. Vinereanu, D. Sinescu, C.-J. Macarie, C. Popescu, R. Daha, I. Dan, G.-A. Stanescu, C. Dan, A. Craiu, E. Nechita, E. Aursulesei, V. Christodorescu, R. Otasevic, P. Simeunovic, D. Ristic, A.D. Celic, V. Pavlovic-Kleut, M. Lazic, J.S. Stojcevski, B. Pencic, B. Stevanovic, A. Andric, A. Iric-Cupic, V. Jovic, M. Davidovic, G. Milanov, S. Mitic, V. Atanaskovic, V. Antic, S. Pavlovic, M. Stanojevic, D. Stoickov, V. Ilic, S. Ilic, M.D. Petrovic, D. Stojsic, S. Kecojevic, S. Dodic, S. Adic, N.C. Cankovic, M. Stojiljkovic, J. Mihajlovic, B. Radin, A. Radovanovic, S. Krotin, M. Klabnik, A. Goncalvesova, E. Pernicky, M. Murin, J. Kovar, F. Kmec, J. Semjanova, H. Strasek, M. Iskra, M.S. Ravnikar, T. Suligoj, N.C. Komel, J. Fras, Z. Jug, B. Glavic, T. Losic, R. Bombek, M. Krajnc, I. Krunic, B. Horvat, S. Kovac, D. Rajtman, D. Cencic, V. Letonja, M. Winkler, R. Valentincic, M. Melihen-Bartolic, C. Bartolic, A. Vrckovnik, M.P. Kladnik, M. Pusnik, C.S. Marolt, A. Klen, J. Drnovsek, B. Leskovar, B. Anguita, M.J.F. Page, J.C.G. Martinez, F.M.S. Andres, J. Bayes-Genis, A. Mirabet, S. Mendez, A. Garcia-Cosio, L. Roig, E. Leon, V. Gonzalez-Costello, J. Muntane, G. Garay, A. Alcade-Martinez, V. Fernandez, S.L. Rivera-Lopez, R. Puga-Martinez, M. Fernandez-Alvarez, M. Serrano-Martinez, J.L. Grille-Cancela, Z. Marzoa-Rivas, R. Blanco-Canosa, P. Paniagua-Martin, M.J. Barge-Caballero, E. Cerdena, I.L. Baldomero, I.F.H. Padron, A.L. Rosillo, S.O. Gonzalez-Gallarza, R.D. Montanes, O.S. Manjavacas, A.M.I. Conde, A.C. Araujo, A. Soria, T. Garcia-Pavia, P. Gomez-Bueno, M. Cobo-Marcos, M. Alonso-Pulpon, L. Cubero, J.S. Sayago, I. Gonzalez-Segovia, A. Briceno, A. Subias, P.E. Hernandez, M.V. Cano, M.J.R. Sanchez, M.A.G. Jimenez, J.F.D. Garrido-Lestache, E.B. Pinilla, J.M.G. de la Villa, B.G. Sahuquillo, A. Marques, R.B. Calvo, F.T. Perez-Martinez, M.T. Gracia-Rodenas, M.R. Garrido-Bravo, I.P. Pastor-Perez, F. Pascual-Figal, D.A. Molina, B.D. Orus, J. Gonzalo, F.E. Bertomeu, V. Valero, R. Martinez-Abellan, R. Quiles, J. Rodrigez-Ortega, J.A. Mateo, I. ElAmrani, A. Fernandez-Vivancos, C. Valero, D.B. Almenar-Bonet, L. Sanchez-Lazaro, I.J. Marques-Sule, E. Facila-Rubio, L. Perez-Silvestre, J. Garcia-Gonzalez, P. Ridocci-Soriano, F. Garcia-Escriva, D. Pellicer-Cabo, A. de la Fuente Galan, L. Diaz, J.L. Platero, A.R. Arias, J.C. Blasco-Peiro, T. Julve, M.S. Sanchez-Insa, E. Aured-Guallar, C. Portoles-Ocampo, A. Melin, M. Hägglund, E. Stenberg, A. Lindahl, I.-M. Asserlund, B. Olsson, L. Dahlström, U. Afzelius, M. Karlström, P. Tengvall, L. Wiklund, P.-A. Olsson, B. Kalayci, S. Temizhan, A. Cavusoglu, Y. Gencer, E. Gunes, H. the European Society of Cardiology Heart Failure Long-Term Registry Investigators Group
Abstract: Aims: This study aimed to assess age- and sex-related differences in management and 1-year risk for all-cause mortality and hospitalization in chronic heart failure (HF) patients. Methods and results: Of 16 354 patients included in the European Society of Cardiology Heart Failure Long-Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline-directed medical therapy (GDMT) were high (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P ≤ 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1-year follow-up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all-cause mortality were lower in women than in men (7.1% vs. 8.7%; P = 0.015), as were rates of all-cause hospitalization (21.9% vs. 27.3%; P 75 years. Conclusions: There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all-cause mortality in patients with LVEF ≤45%. © 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology
Published: 2020

10. Unravelling the interplay between hyperkalaemia, renin–angiotensin–aldosterone inhibitor use and clinical outcomes. Data from 9222 chronic heart failure patients of the ESC-HFA-EORP Heart Failure Long-Term Registry

Author: Rossignol, P. Lainscak, M. Crespo-Leiro, M.G. Laroche, C. Piepoli, M.F. Filippatos, G. Rosano, G.M.C. Savarese, G. Anker, S.D. Seferovic, P.M. Ruschitzka, F. Coats, A.J.S. Mebazaa, A. McDonagh, T. Sahuquillo, A. Penco, M. Maggioni, A.P. Lund, L.H. Christopher Peter Gale, G.B. Branko Beleslin, R.S. Andrzej Budaj, P.L. Ovidiu Chioncel, R.O. Nikolaos Dagres, D.E. Nicolas Danchin, F.R. David Erlinge, S.E. Jonathan Emberson, G.B. Michael Glikson, I.L. Alastair Gray, G.B. Meral Kayikcioglu, T.R. Aldo Maggioni, I.T. Klaudia Vivien Nagy, H.U. Aleksandr Nedoshivin, R.U. Anna-Sonia Petronio, I.T. Jolien Roos-Hesselink, N.L. Lars Wallentin, S.E. Uwe Zeymer, D.E. Anker, S. Mebazaa, A. Coats, A. Filippatos, G. Ferrari, R. Maggioni, A.P. Goda, A. Diez, M. Fernandez, A. Fruhwald, F. Fazlibegovic, E. Gatzov, P. Kurlianskaya, A. Hullin, R. Christodoulides, T. Hradec, J. Nielsen, O.W. Nedjar, R. Uuetoa, T. Hassanein, M. Jimenez, J.F.D. Harjola, V.P. Logeart, D. Chumburidze, V. Tousoulis, D. Milicic, D. Merkely, B. O'Donoghue, E. Amir, O. Shotan, A. Shafie, D. Metra, M. Matsumori, A. Mirrakhimov, E. Kavoliuniene, A. Erglis, A. Vataman, E. Otljanska, M. Kostovska, E.S. DeMarco, D.C. Drozdz, J. Fonseca, C. Chioncel, O. Dekleva, M. Shkolnik, E. Dahlstrom, U. Lainscak, M. Goncalvesova, E. Temizhan, A. Estrago, V. Bajraktari, G. Auer, J. Ablasser, K. Fruhwald, F. Dolze, T. Brandner, K. Gstrein, S. Poelzl, G. Moertl, D. Reiter, S. Podczeck-Schweighofer, A. Muslibegovic, A. Vasilj, M. Fazlibegovic, E. Cesko, M. Zelenika, D. Palic, B. Pravdic, D. Cuk, D. Vitlianova, K. Katova, T. Velikov, T. Kurteva, T. Gatzov, P. Kamenova, D. Antova, M. Sirakova, V. Krejci, J. Mikolaskova, M. Spinar, J. Krupicka, J. Malek, F. Hegarova, M. Lazarova, M. Monhart, Z. Hassanein, M. Sobhy, M. El Messiry, F. El Shazly, A.H. Elrakshy, Y. Youssef, A. Moneim, A.A. Noamany, M. Reda, A. Dayem, T.K.A. Farag, N. Halawa, S.I. Hamid, M.A. Said, K. Saleh, A. Ebeid, H. Hanna, R. Aziz, R. Louis, O. Enen, M.A. Ibrahim, B.S. Nasr, G. Elbahry, A. Sobhy, H. Ashmawy, M. Gouda, M. Aboleineen, W. Bernard, Y. Luporsi, P. Meneveau, N. Pillot, M. Morel, M. Seronde, M.-F. Schiele, F. Briand, F. Delahaye, F. Damy, T. Eicher, J.-C. de Groote, P. Fertin, M. Lamblin, N. Isnard, R. Lefol, C. Thevenin, S. Hagege, A. Jondeau, G. Logeart, D. Le Marcis, V. Ly, J.-F. Coisne, D. Lequeux, B. Le Moal, V. Mascle, S. Lotton, P. Behar, N. Donal, E. Thebault, C. Ridard, C. Reynaud, A. Basquin, A. Bauer, F. Codjia, R. Galinier, M. Tourikis, P. Stavroula, M. Tousoulis, D. Stefanadis, C. Chrysohoou, C. Kotrogiannis, I. Matzaraki, V. Dimitroula, T. Karavidas, A. Tsitsinakis, G. Kapelios, C. Nanas, J. Kampouri, H. Nana, E. Kaldara, E. Eugenidou, A. Vardas, P. Saloustros, I. Patrianakos, A. Tsaknakis, T. Evangelou, S. Nikoloulis, N. Tziourganou, H. Tsaroucha, A. Papadopoulou, A. Douras, A. Polgar, L. Kosztin, A. Nyolczas, N. Nagy, A.C. Halmosi, R. Elber, J. Alony, I. Shotan, A. Fuhrmann, A.V. Amir, O. Romano, S. Marcon, S. Penco, M. Di Mauro, M. Lemme, E. Carubelli, V. Rovetta, R. Bulgari, M. Quinzani, F. Lombardi, C. Bosi, S. Schiavina, G. Squeri, A. Barbieri, A. Di Tano, G. Pirelli, S. Ferrari, R. Fucili, A. Passero, T. Musio, S. Di Biase, M. Correale, M. Salvemini, G. Brognoli, S. Zanelli, E. Giordano, A. Agostoni, P. Italiano, G. Salvioni, E. Copelli, S. Modena, M.G. Reggianini, L. Valenti, C. Olaru, A. Bandino, S. Deidda, M. Mercuro, G. Dessalvi, C.C. Marino, P.N. Di Ruocco, M.V. Sartori, C. Piccinino, C. Parrinello, G. Licata, G. Torres, D. Giambanco, S. Busalacchi, S. Arrotti, S. Novo, S. Inciardi, R.M. Pieri, P. Chirco, P.R. Galifi, M.A. Teresi, G. Buccheri, D. Minacapelli, A. Veniani, M. Frisinghelli, A. Priori, S.G. Cattaneo, S. Opasich, C. Gualco, A. Pagliaro, M. Mancone, M. Fedele, F. Cinque, A. Vellini, M. Scarfo, I. Romeo, F. Ferraiuolo, F. Sergi, D. Anselmi, M. Melandri, F. Leci, E. Iori, E. Bovolo, V. Pidello, S. Frea, S. Bergerone, S. Botta, M. Canavosio, F.G. Gaita, F. 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Kleinrok, A. Aguiar, C.T. Ventosa, A. Pereira, S. Faria, R. Chin, J. De Jesus, I. Santos, R. Silva, P. Moreno, N. Queirós, C. Lourenço, C. Pereira, A. Castro, A. Andrade, A. Guimaraes, T.O. Martins, S. Placido, R. Lima, G. Brito, D. Francisco, A.R. Cardiga, R. Proenca, M. Araujo, I. Marques, F. Fonseca, C. Moura, B. Leite, S. Campelo, M. Silva-Cardoso, J. Rodrigues, J. Rangel, I. Martins, E. Correia, A.S. Peres, M. Marta, L. da Silva, G.F. Severino, D. Durao, D. Leao, S. Magalhaes, P. Moreira, I. Cordeiro, A.F. Ferreira, C. Araujo, C. Ferreira, A. Baptista, A. Radoi, M. Bicescu, G. Vinereanu, D. Sinescu, C.-J. Macarie, C. Popescu, R. Daha, I. Dan, G.-A. Stanescu, C. Dan, A. Craiu, E. Nechita, E. Aursulesei, V. Christodorescu, R. Otasevic, P. Seferovic, P.M. Simeunovic, D. Ristic, A.D. Celic, V. Pavlovic-Kleut, M. Lazic, J.S. Stojcevski, B. Pencic, B. Stevanovic, A. Andric, A. Simić, D. Ašanin, M. Iric-Cupic, V. Jovic, M. Davidovic, G. Milanov, S. Mitic, V. Atanaskovic, V. Antic, S. Pavlovic, M. Stanojevic, D. Stoickov, V. Ilic, S. Ilic, M.D. Petrovic, D. Stojsic, S. Kecojevic, S. Dodic, S. Adic, N.C. Cankovic, M. Stojiljkovic, J. Mihajlovic, B. Radin, A. Radovanovic, S. Krotin, M. Klabnik, A. Goncalvesova, E. Pernicky, M. Murin, J. Kovar, F. Kmec, J. Semjanova, H. Strasek, M. Iskra, M.S. Ravnikar, T. Suligoj, N.C. Komel, J. Fras, Z. Jug, B. Glavic, T. Losic, R. Bombek, M. Krajnc, I. Krunic, B. Horvat, S. Kovac, D. Rajtman, D. Cencic, V. Letonja, M. Winkler, R. Valentincic, M. Melihen-Bartolic, C. Bartolic, A. Vrckovnik, M.P. Kladnik, M. Pusnik, C.S. Marolt, A. Klen, J. Drnovsek, B. Leskovar, B. Anguita, M.J.F. Page, J.C.G. Martinez, F.M.S. Andres, J. Bayes-Genis, A. Mirabet, S. Mendez, A. Garcia-Cosio, L. Roig, E. Leon, V. Gonzalez-Costello, J. Muntane, G. Garay, A. Alcade-Martinez, V. Fernandez, S.L. Rivera-Lopez, R. Puga-Martinez, M. Fernandez-Alvarez, M. Serrano-Martinez, J.L. Grille-Cancela, Z. Marzoa-Rivas, R. Blanco-Canosa, P. Paniagua-Martin, M.J. Barge-Caballero, E. Cerdena, I.L. Baldomero, I.F.H. Padron, A.L. Rosillo, S.O. Gonzalez-Gallarza, R.D. Montanes, O.S. Manjavacas, A.M.I. Conde, A.C. Araujo, A. Soria, T. Garcia-Pavia, P. Gomez-Bueno, M. Cobo-Marcos, M. Alonso-Pulpon, L. Cubero, J.S. Sayago, I. Gonzalez-Segovia, A. Briceno, A. Subias, P.E. Hernandez, M.V. Cano, M.J.R. Sanchez, M.A.G. Jimenez, J.F.D. Garrido-Lestache, E.B. Pinilla, J.M.G. de la Villa, B.G. Sahuquillo, A. Marques, R.B. Calvo, F.T. Perez-Martinez, M.T. Gracia-Rodenas, M.R. Garrido-Bravo, I.P. Pastor-Perez, F. Pascual-Figal, D.A. Molina, B.D. Orus, J. Gonzalo, F.E. Bertomeu, V. Valero, R. Martinez-Abellan, R. Quiles, J. Rodrigez-Ortega, J.A. Mateo, I. ElAmrani, A. Fernandez-Vivancos, C. Valero, D.B. Almenar-Bonet, L. Sanchez-Lazaro, I.J. Marques-Sule, E. Facila-Rubio, L. Perez-Silvestre, J. Garcia-Gonzalez, P. Ridocci-Soriano, F. Garcia-Escriva, D. Pellicer-Cabo, A. de la Fuente Galan, L. Diaz, J.L. Platero, A.R. Arias, J.C. Blasco-Peiro, T. Julve, M.S. Sanchez-Insa, E. Aured-Guallar, C. Portoles-Ocampo, A. Melin, M. Hägglund, E. Stenberg, A. Lindahl, I.-M. Asserlund, B. Olsson, L. Dahlström, U. Afzelius, M. Karlström, P. Tengvall, L. Olsson, B. Kalayci, S. Temizhan, A. Cavusoglu, Y. Gencer, E. Yilmaz, M.B. Gunes, H.
Subjects: cardiovascular diseases
Abstract: Aims: We assessed the interplay between hyperkalaemia (HK) and renin–angiotensin–aldosterone system inhibitor (RAASi) use, dose and discontinuation, and their association with all-cause or cardiovascular death in patients with chronic heart failure (HF). We hypothesized that HK-associated increased death may be related to RAASi withdrawal. Methods and results: The ESC-HFA-EORP Heart Failure Long-Term Registry was used. Among 9222 outpatients (HF with reduced ejection fraction: 60.6%, HF with mid-range ejection fraction: 22.9%, HF with preserved ejection fraction: 16.5%) from 31 countries, 16.6% had HK (≥5.0 mmol/L) at baseline. Angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) was used in 88.3%, a mineralocorticoid receptor antagonist (MRA) in 58.7%, or a combination in 53.2%; of these, at ≥50% of target dose in ACEi: 61.8%; ARB: 64.7%; and MRA: 90.3%. At a median follow-up of 12.2 months, there were 789 deaths (8.6%). Both hypokalaemia and HK were independently. associated with higher mortality, and ACEi/ARB prescription at baseline with lower mortality. MRA prescription was not retained in the model. In multivariable analyses, HK at baseline was independently associated with MRA non-prescription at baseline and subsequent discontinuation. When considering subsequent discontinuation of RAASi (instead of baseline use), HK was no longer found associated with all-cause deaths. Importantly, all RAASi (ACEi, ARB, or MRA) discontinuations were strongly associated with mortality. Conclusions: In HF, hyper- and hypokalaemia were associated with mortality. However, when adjusting for RAASi discontinuation, HK was no longer associated with mortality, suggesting that HK may be a risk marker for RAASi discontinuation rather than a risk factor for worse outcomes. © 2020 European Society of Cardiology
Published: 2020

11. High-resolution oligonucleotide array-CGH applied to the detection and characterization of large rearrangements in the hereditary breast cancer gene BRCA1

Author: Rouleau, E, Lefol, C, Tozlu, S, Andrieu, C, Guy, C, Copigny, F, Nogues, C, Bieche, I, and Lidereau, R
Published: 2007

12. Acute heart failure congestion and perfusion status – impact of the clinical classification on in-hospital and long-term outcomes; insights from the ESC-EORP-HFA Heart Failure Long-Term Registry

Author: Chioncel, O. Mebazaa, A. Maggioni, A.P. Harjola, V.-P. Rosano, G. Laroche, C. Piepoli, M.F. Crespo-Leiro, M.G. Lainscak, M. Ponikowski, P. Filippatos, G. Ruschitzka, F. Seferovic, P. Coats, A.J.S. Lund, L.H. Auer, J. Ablasser, K. Fruhwald, F. Dolze, T. Brandner, K. Gstrein, S. Poelzl, G. Moertl, D. Reiter, S. Podczeck-Schweighofer, A. Muslibegovic, A. Vasilj, M. Fazlibegovic, E. Cesko, M. Zelenika, D. Palic, B. Pravdic, D. Cuk, D. Vitlianova, K. Katova, T. Velikov, T. Kurteva, T. Gatzov, P. Kamenova, D. Antova, M. Sirakova, V. Krejci, J. Mikolaskova, M. Spinar, J. Krupicka, J. Malek, F. Hegarova, M. Lazarova, M. Monhart, Z. Hassanein, M. Sobhy, M. El Messiry, F. El Shazly, A.H. Elrakshy, Y. Youssef, A. Moneim, A.A. Noamany, M. Reda, A. Dayem, T.K.A. Farag, N. Halawa, S.I. Hamid, M.A. Said, K. Saleh, A. Ebeid, H. Hanna, R. Aziz, R. Louis, O. Enen, M.A. Ibrahim, B.S. Nasr, G. Elbahry, A. Sobhy, H. Ashmawy, M. Gouda, M. Aboleineen, W. Bernard, Y. Luporsi, P. Meneveau, N. Pillot, M. Morel, M. Seronde, M.-F. Schiele, F. Briand, F. Delahaye, F. Damy, T. Eicher, J.-C. de Groote, P. Fertin, M. Lamblin, N. Isnard, R. Lefol, C. Thevenin, S. Hagege, A. Jondeau, G. Logeart, D. Le Marcis, V. Ly, J.-F. Coisne, D. Lequeux, B. Le Moal, V. Mascle, S. Lotton, P. Behar, N. Donal, E. Thebault, C. Ridard, C. Reynaud, A. Basquin, A. Bauer, F. Codjia, R. Galinier, M. Tourikis, P. Stavroula, M. Tousoulis, D. Stefanadis, C. Chrysohoou, C. Kotrogiannis, I. Matzaraki, V. Dimitroula, T. Karavidas, A. Tsitsinakis, G. Kapelios, C. Nanas, J. Kampouri, H. Nana, E. Kaldara, E. Eugenidou, A. Vardas, P. Saloustros, I. Patrianakos, A. Tsaknakis, T. Evangelou, S. Nikoloulis, N. Tziourganou, H. Tsaroucha, A. Papadopoulou, A. Douras, A. Polgar, L. Merkely, B. Kosztin, A. Nyolczas, N. Nagy, A.C. Halmosi, R. Elber, J. Alony, I. Shotan, A. Fuhrmann, A.V. Amir, O. Romano, S. Marcon, S. Penco, M. Di Mauro, M. Lemme, E. Carubelli, V. Rovetta, R. Metra, M. Bulgari, M. Quinzani, F. Lombardi, C. Bosi, S. Schiavina, G. Squeri, A. Barbieri, A. Di Tano, G. Pirelli, S. Ferrari, R. Fucili, A. Passero, T. Musio, S. Di Biase, M. Correale, M. Salvemini, G. Brognoli, S. Zanelli, E. Giordano, A. Agostoni, P. Italiano, G. Salvioni, E. Copelli, S. Modena, M.G. Reggianini, L. Valenti, C. Olaru, A. Bandino, S. Deidda, M. Mercuro, G. Dessalvi, C.C. Marino, P.N. Di Ruocco, M.V. Sartori, C. Piccinino, C. Parrinello, G. Licata, G. Torres, D. Giambanco, S. Busalacchi, S. Arrotti, S. Novo, S. Inciardi, R.M. Pieri, P. Chirco, P.R. Galifi, M.A. Teresi, G. Buccheri, D. Minacapelli, A. Veniani, M. Frisinghelli, A. Priori, S.G. Cattaneo, S. Opasich, C. Gualco, A. Pagliaro, M. Mancone, M. Fedele, F. Cinque, A. Vellini, M. Scarfo, I. Romeo, F. Ferraiuolo, F. Sergi, D. Anselmi, M. Melandri, F. Leci, E. Iori, E. Bovolo, V. Pidello, S. Frea, S. Bergerone, S. Botta, M. Canavosio, F.G. Gaita, F. Merlo, M. Cinquetti, M. Sinagra, G. Ramani, F. Fabris, E. Stolfo, D. Artico, J. Miani, D. Fresco, C. Daneluzzi, C. Proclemer, A. Cicoira, M. Zanolla, L. Marchese, G. Torelli, F. Vassanelli, C. Voronina, N. Erglis, A. Tamakauskas, V. Smalinskas, V. Karaliute, R. Petraskiene, I. Kazakauskaite, E. Rumbinaite, E. Kavoliuniene, A. Vysniauskas, V. Brazyte-Ramanauskiene, R. Petraskiene, D. Stankala, S. Switala, P. Juszczyk, Z. Sinkiewicz, W. Gilewski, W. Pietrzak, J. Orzel, T. Kasztelowicz, P. Kardaszewicz, P. Lazorko-Piega, M. Gabryel, J. Mosakowska, K. Bellwon, J. Rynkiewicz, A. Raczak, G. Lewicka, E. Dabrowska-Kugacka, A. Bartkowiak, R. Sosnowska-Pasiarska, B. Wozakowska-Kaplon, B. Krzeminski, A. Zabojszcz, M. Mirek-Bryniarska, E. Grzegorzko, A. Bury, K. Nessler, J. Zalewski, J. Furman, A. Broncel, M. Poliwczak, A. Bala, A. Zycinski, P. Rudzinska, M. Jankowski, L. Kasprzak, J.D. Michalak, L. Soska, K.W. Drozdz, J. Huziuk, I. Retwinski, A. Flis, P. Weglarz, J. Bodys, A. Grajek, S. Kaluzna-Oleksy, M. Straburzynska-Migaj, E. Dankowski, R. Szymanowska, K. Grabia, J. Szyszka, A. Nowicka, A. Samcik, M. Wolniewicz, L. Baczynska, K. Komorowska, K. Poprawa, I. Komorowska, E. Sajnaga, D. Zolbach, A. Dudzik-Plocica, A. Abdulkarim, A.-F. Lauko-Rachocka, A. Kaminski, L. Kostka, A. Cichy, A. Ruszkowski, P. Splawski, M. Fitas, G. Szymczyk, A. Serwicka, A. Fiega, A. Zysko, D. Krysiak, W. Szabowski, S. Skorek, E. Pruszczyk, P. Bienias, P. Ciurzynski, M. Welnicki, M. Mamcarz, A. Folga, A. Zielinski, T. Rywik, T. Leszek, P. Sobieszczanska-Malek, M. Piotrowska, M. Kozar-Kaminska, K. Komuda, K. Wisniewska, J. Tarnowska, A. Balsam, P. Marchel, M. Opolski, G. Kaplon-Cieslicka, A. Gil, R.J. Mozenska, O. Byczkowska, K. Gil, K. Pawlak, A. Michalek, A. Krzesinski, P. Piotrowicz, K. Uzieblo-Zyczkowska, B. Stanczyk, A. Skrobowski, A. Jankowska, E. Rozentryt, P. Polonski, L. Gadula-Gacek, E. Nowalany-Kozielska, E. Kuczaj, A. Kalarus, Z. Szulik, M. Przybylska, K. Klys, J. Prokop-Lewicka, G. Kleinrok, A. Aguiar, C.T. Ventosa, A. Pereira, S. Faria, R. Chin, J. De Jesus, I. Santos, R. Silva, P. Moreno, N. Queirós, C. Lourenço, C. Pereira, A. Castro, A. Andrade, A. Guimaraes, T.O. Martins, S. Placido, R. Lima, G. Brito, D. Francisco, A.R. Cardiga, R. Proenca, M. Araujo, I. Marques, F. Fonseca, C. Moura, B. Leite, S. Campelo, M. Silva-Cardoso, J. Rodrigues, J. Rangel, I. Martins, E. Correia, A.S. Peres, M. Marta, L. da Silva, G.F. Severino, D. Durao, D. Leao, S. Magalhaes, P. Moreira, I. Cordeiro, A.F. Ferreira, C. Araujo, C. Ferreira, A. Baptista, A. Radoi, M. Bicescu, G. Vinereanu, D. Sinescu, C.-J. Macarie, C. Popescu, R. Daha, I. Dan, G.-A. Stanescu, C. Dan, A. Craiu, E. Nechita, E. Aursulesei, V. Christodorescu, R. Otasevic, P. Seferovic, P.M. Simeunovic, D. Ristic, A.D. Celic, V. Pavlovic-Kleut, M. Lazic, J.S. Stojcevski, B. Pencic, B. Stevanovic, A. Andric, A. Iric-Cupic, V. Jovic, M. Davidovic, G. Milanov, S. Mitic, V. Atanaskovic, V. Antic, S. Pavlovic, M. Stanojevic, D. Stoickov, V. Ilic, S. Ilic, M.D. Petrovic, D. Stojsic, S. Kecojevic, S. Dodic, S. Adic, N.C. Cankovic, M. Stojiljkovic, J. Mihajlovic, B. Radin, A. Radovanovic, S. Krotin, M. Klabnik, A. Goncalvesova, E. Pernicky, M. Murin, J. Kovar, F. Kmec, J. Semjanova, H. Strasek, M. Iskra, M.S. Ravnikar, T. Suligoj, N.C. Komel, J. Fras, Z. Jug, B. Glavic, T. Losic, R. Bombek, M. Krajnc, I. Krunic, B. Horvat, S. Kovac, D. Rajtman, D. Cencic, V. Letonja, M. Winkler, R. Valentincic, M. Melihen-Bartolic, C. Bartolic, A. Vrckovnik, M.P. Kladnik, M. Pusnik, C.S. Marolt, A. Klen, J. Drnovsek, B. Leskovar, B. Anguita, M.J.F. Page, J.C.G. Martinez, F.M.S. Andres, J. Bayes-Genis, A. Mirabet, S. Mendez, A. Garcia-Cosio, L. Roig, E. Leon, V. Gonzalez-Costello, J. Muntane, G. Garay, A. Alcade-Martinez, V. Fernandez, S.L. Rivera-Lopez, R. Puga-Martinez, M. Fernandez-Alvarez, M. Serrano-Martinez, J.L. Crespo-Leiro, M. Grille-Cancela, Z. Marzoa-Rivas, R. Blanco-Canosa, P. Paniagua-Martin, M.J. Barge-Caballero, E. Cerdena, I.L. Baldomero, I.F.H. Padron, A.L. Rosillo, S.O. Gonzalez-Gallarza, R.D. Montanes, O.S. Manjavacas, A.M.I. Conde, A.C. Araujo, A. Soria, T. Garcia-Pavia, P. Gomez-Bueno, M. Cobo-Marcos, M. Alonso-Pulpon, L. Cubero, J.S. Sayago, I. Gonzalez-Segovia, A. Briceno, A. Subias, P.E. Hernandez, M.V. Cano, M.J.R. Sanchez, M.A.G. Jimenez, J.F.D. Garrido-Lestache, E.B. Pinilla, J.M.G. de la Villa, B.G. Sahuquillo, A. Marques, R.B. Calvo, F.T. Perez-Martinez, M.T. Gracia-Rodenas, M.R. Garrido-Bravo, I.P. Pastor-Perez, F. Pascual-Figal, D.A. Molina, B.D. Orus, J. Gonzalo, F.E. Bertomeu, V. Valero, R. Martinez-Abellan, R. Quiles, J. Rodrigez-Ortega, J.A. Mateo, I. ElAmrani, A. Fernandez-Vivancos, C. Valero, D.B. Almenar-Bonet, L. Sanchez-Lazaro, I.J. Marques-Sule, E. Facila-Rubio, L. Perez-Silvestre, J. Garcia-Gonzalez, P. Ridocci-Soriano, F. Garcia-Escriva, D. Pellicer-Cabo, A. de la Fuente Galan, L. Diaz, J.L. Platero, A.R. Arias, J.C. Blasco-Peiro, T. Julve, M.S. Sanchez-Insa, E. Aured-Guallar, C. Portoles-Ocampo, A. Melin, M. Hägglund, E. Stenberg, A. Lindahl, I.-M. Asserlund, B. Olsson, L. Dahlström, U. Afzelius, M. Karlström, P. Tengvall, L. Wiklund, P.-A. Olsson, B. Kalayci, S. Temizhan, A. Cavusoglu, Y. Gencer, E. Yilmaz, M.B. Gunes, H. on behalf of the ESC-EORP-HFA Heart Failure Long-Term Registry Investigators
Abstract: Aims: Classification of acute heart failure (AHF) patients into four clinical profiles defined by evidence of congestion and perfusion is advocated by the 2016 European Society of Cardiology (ESC)guidelines. Based on the ESC-EORP-HFA Heart Failure Long-Term Registry, we compared differences in baseline characteristics, in-hospital management and outcomes among congestion/perfusion profiles using this classification. Methods and results: We included 7865 AHF patients classified at admission as: ‘dry-warm’ (9.9%), ‘wet-warm’ (69.9%), ‘wet-cold’ (19.8%) and ‘dry-cold’ (0.4%). These groups differed significantly in terms of baseline characteristics, in-hospital management and outcomes. In-hospital mortality was 2.0% in ‘dry-warm’, 3.8% in ‘wet-warm’, 9.1% in ‘dry-cold’ and 12.1% in ‘wet-cold’ patients. Based on clinical classification at admission, the adjusted hazard ratios (95% confidence interval) for 1-year mortality were: ‘wet-warm’ vs. ‘dry-warm’ 1.78 (1.43–2.21) and ‘wet-cold’ vs. ‘wet-warm’ 1.33 (1.19–1.48). For profiles resulting from discharge classification, the adjusted hazard ratios (95% confidence interval) for 1-year mortality were: ‘wet-warm’ vs. ‘dry-warm’ 1.46 (1.31–1.63) and ‘wet-cold’ vs. ‘wet-warm’ 2.20 (1.89–2.56). Among patients discharged alive, 30.9% had residual congestion, and these patients had higher 1-year mortality compared to patients discharged without congestion (28.0 vs. 18.5%). Tricuspid regurgitation, diabetes, anaemia and high New York Heart Association class were independently associated with higher risk of congestion at discharge, while beta-blockers at admission, de novo heart failure, or any cardiovascular procedure during hospitalization were associated with lower risk of residual congestion. Conclusion: Classification based on congestion/perfusion status provides clinically relevant information at hospital admission and discharge. A better understanding of the clinical course of the two entities could play an important role towards the implementation of targeted strategies that may improve outcomes. © 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology
Published: 2019

13. Performance of Prognostic Risk Scores in Chronic Heart Failure Patients Enrolled in the European Society of Cardiology Heart Failure Long-Term Registry

Author: Canepa, Marco, primary, Fonseca, Candida, additional, Chioncel, Ovidiu, additional, Laroche, Cécile, additional, Crespo-Leiro, Maria G., additional, Coats, Andrew J.S., additional, Mebazaa, Alexandre, additional, Piepoli, Massimo F., additional, Tavazzi, Luigi, additional, Maggioni, Aldo P., additional, Crespo-Leiro, M., additional, Anker, S., additional, Mebazaa, A., additional, Coats, A., additional, Filippatos, G., additional, Ferrari, R., additional, Maggioni, A.P., additional, Piepoli, M.F., additional, Amir, O., additional, Chioncel, O., additional, Dahlström, U., additional, Delgado Jimenez, J.F., additional, Drozdz, J., additional, Erglis, A., additional, Fazlibegovic, E., additional, Fonseca, C., additional, Fruhwald, F., additional, Gatzov, P., additional, Goncalvesova, E., additional, Hassanein, M., additional, Hradec, J., additional, Kavoliuniene, A., additional, Lainscak, M., additional, Logeart, D., additional, Merkely, B., additional, Metra, M., additional, Otljanska, M., additional, Seferovic, P.M., additional, Srbinovska Kostovska, E., additional, Temizhan, A., additional, Tousoulis, D., additional, Ferreira, T., additional, Andarala, M., additional, Fiorucci, E., additional, Folkesson Lefrancq, E., additional, Glémot, M., additional, Gracia, G., additional, Konte, M., additional, Laroche, C., additional, McNeill, P.A., additional, Missiamenou, V., additional, Taylor, C., additional, Auer, J., additional, Ablasser, K., additional, Dolze, T., additional, Brandner, K., additional, Gstrein, S., additional, Poelzl, G., additional, Moertl, D., additional, Reiter, S., additional, Podczeck-Schweighofer, A., additional, Muslibegovic, A., additional, Vasilj, M., additional, Cesko, M., additional, Zelenika, D., additional, Palic, B., additional, Pravdic, D., additional, Cuk, D., additional, Vitlianova, K., additional, Katova, T., additional, Velikov, T., additional, Kurteva, T., additional, Kamenova, D., additional, Antova, M., additional, Sirakova, V., additional, Krejci, J., additional, Mikolaskova, M., additional, Spinar, J., additional, Krupicka, J., additional, Malek, F., additional, Hegarova, M., additional, Lazarova, M., additional, Monhart, Z., additional, Sobhy, M., additional, El Messiry, F., additional, El Shazly, A.H., additional, Elrakshy, Y., additional, Youssef, A., additional, Moneim, A.A., additional, Noamany, M., additional, Reda, A., additional, Abdel Dayem, T.K., additional, Farag, N., additional, Ibrahim Halawa, S., additional, Abdel Hamid, M., additional, Said, K., additional, Saleh, A., additional, Ebeid, H., additional, Hanna, R., additional, Aziz, R., additional, Louis, O., additional, Enen, M.A., additional, Ibrahim, B.S., additional, Nasr, G., additional, Elbahry, A., additional, Sobhy, H., additional, Ashmawy, M., additional, Gouda, M., additional, Aboleineen, W., additional, Bernard, Y., additional, Luporsi, P., additional, Meneveau, N., additional, Pillot, M., additional, Morel, M., additional, Seronde, M.-F., additional, Schiele, F., additional, Briand, F., additional, Delahaye, F., additional, Damy, T., additional, Eicher, J.-C., additional, de Groote, P., additional, Fertin, M., additional, Lamblin, N., additional, Isnard, R., additional, Lefol, C., additional, Thevenin, S., additional, Hagege, A., additional, Jondeau, G., additional, Le Marcis, V., additional, Ly, J.-F., additional, Coisne, D., additional, Lequeux, B., additional, Le Moal, V., additional, Mascle, S., additional, Lotton, P., additional, Behar, N., additional, Donal, E., additional, Thebault, C., additional, Ridard, C., additional, Reynaud, A., additional, Basquin, A., additional, Bauer, F., additional, Codjia, R., additional, Galinier, M., additional, Tourikis, P., additional, Stavroula, M., additional, Stefanadis, C., additional, Chrysohoou, C., additional, Kotrogiannis, I., additional, Matzaraki, V., additional, Dimitroula, T., additional, Karavidas, A., additional, Tsitsinakis, G., 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Placido, R., additional, Lima, G., additional, Brito, D., additional, Francisco, A.R., additional, Cardiga, R., additional, Proenca, M., additional, Araujo, I., additional, Marques, F., additional, Moura, B., additional, Leite, S., additional, Campelo, M., additional, Silva-Cardoso, J., additional, Rodrigues, J., additional, Rangel, I., additional, Martins, E., additional, Sofia Correia, A., additional, Peres, M., additional, Marta, L., additional, Ferreira da Silva, G., additional, Severino, D., additional, Durao, D., additional, Leao, S., additional, Magalhaes, P., additional, Moreira, I., additional, Filipa Cordeiro, A., additional, Ferreira, C., additional, Araujo, C., additional, Ferreira, A., additional, Baptista, A., additional, Radoi, M., additional, Bicescu, G., additional, Vinereanu, D., additional, Sinescu, C.-J., additional, Macarie, C., additional, Popescu, R., additional, Daha, I., additional, Dan, G.-A., additional, Stanescu, C., additional, Dan, A., additional, Craiu, E., additional, Nechita, E., additional, Aursulesei, V., additional, Christodorescu, R., additional, Otasevic, P., additional, Simeunovic, D., additional, Ristic, A.D., additional, Celic, V., additional, Pavlovic-Kleut, M., additional, Suzic Lazic, J., additional, Stojcevski, B., additional, Pencic, B., additional, Stevanovic, A., additional, Andric, A., additional, Iric-Cupic, V., additional, Jovic, M., additional, Davidovic, G., additional, Milanov, S., additional, Mitic, V., additional, Atanaskovic, V., additional, Antic, S., additional, Pavlovic, M., additional, Stanojevic, D., additional, Stoickov, V., additional, Ilic, S., additional, Deljanin Ilic, M., additional, Petrovic, D., additional, Stojsic, S., additional, Kecojevic, S., additional, Dodic, S., additional, Cemerlic Adic, N., additional, Cankovic, M., additional, Stojiljkovic, J., additional, Mihajlovic, B., additional, Radin, A., additional, Radovanovic, S., additional, Krotin, M., additional, Klabnik, A., additional, Pernicky, M., additional, Murin, J., additional, Kovar, F., additional, Kmec, J., additional, Semjanova, H., additional, Strasek, M., additional, Savnik Iskra, M., additional, Ravnikar, T., additional, Cernic Suligoj, N., additional, Komel, J., additional, Fras, Z., additional, Jug, B., additional, Glavic, T., additional, Losic, R., additional, Bombek, M., additional, Krajnc, I., additional, Krunic, B., additional, Horvat, S., additional, Kovac, D., additional, Rajtman, D., additional, Cencic, V., additional, Letonja, M., additional, Winkler, R., additional, Valentincic, M., additional, Melihen-Bartolic, C., additional, Bartolic, A., additional, Pusnik Vrckovnik, M., additional, Kladnik, M., additional, Slemenik Pusnik, C., additional, Marolt, A., additional, Klen, J., additional, Drnovsek, B., additional, Leskovar, B., additional, Fernandez Anguita, M.J., additional, Gallego Page, J.C., additional, Salmeron Martinez, F.M., additional, Andres, J., additional, Genis, A.B., additional, Mirabet, S., additional, Mendez, A., additional, Garcia-Cosio, L., additional, Roig, E., additional, Leon, V., additional, Gonzalez-Costello, J., additional, Muntane, G., additional, Garay, A., additional, Alcade-Martinez, V., additional, Lopez Fernandez, S., additional, Rivera-Lopez, R., additional, Puga-Martinez, M., additional, Fernandez-Alvarez, M., additional, Serrano-Martinez, J.L., additional, Grille-Cancela, Z., additional, Marzoa-Rivas, R., additional, Blanco-Canosa, P., additional, Paniagua-Martin, M.J., additional, Barge-Caballero, E., additional, Laynez Cerdena, I., additional, Famara Hernandez Baldomero, I., additional, Lara Padron, A., additional, Ofelia Rosillo, S., additional, Dalmau Gonzalez-Gallarza, R., additional, Salvador Montanes, O., additional, Iniesta Manjavacas, A.M., additional, Castro Conde, A., additional, Araujo, A., additional, Soria, T., additional, Garcia-Pavia, P., additional, Gomez-Bueno, M., additional, Cobo-Marcos, M., additional, Alonso-Pulpon, L., additional, Segovia Cubero, J., additional, Sayago, I., additional, Gonzalez-Segovia, A., additional, Briceno, A., additional, Escribano Subias, P., additional, Vicente Hernandez, M., additional, Ruiz Cano, M.J., additional, Gomez Sanchez, M.A., additional, Barrios Garrido-Lestache, E., additional, Garcia Pinilla, J.M., additional, Garcia de la Villa, B., additional, Sahuquillo, A., additional, Bravo Marques, R., additional, Torres Calvo, F., additional, Perez-Martinez, M.T., additional, Gracia-Rodenas, M.R., additional, Garrido-Bravo, I.P., additional, Pastor-Perez, F., additional, Pascual-Figal, D.A., additional, Diaz Molina, B., additional, Orus, J., additional, Epelde Gonzalo, F., additional, Bertomeu, V., additional, Valero, R., additional, Martinez-Abellan, R., additional, Quiles, J., additional, Rodrigez-Ortega, J.A., additional, Mateo, I., additional, ElAmrani, A., additional, Fernandez-Vivancos, C., additional, Bierge Valero, D., additional, Almenar-Bonet, L., additional, 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Published: 2018
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14. Are hospitalized or ambulatory patients with heart failure treated in accordance with European Society of Cardiology guidelines? Evidence from 12 440 patients of the ESC Heart Failure Long-Term Registry

Author: Maggioni, Aldo P, Anker, Stefan D., Dahlström, Ulf, Filippatos, Gerasimos, Ponikowski, Piotr, Zannad, Faiez, Amir, Offer, Chioncel, Ovidiu, Leiro, Marisa Crespo, Drozdz, Jaroslaw, Erglis, Andrejs, Fazlibegovic, Emir, Fonseca, Candida, Fruhwald, Friedrich, Gatzov, Plamen, Goncalvesova, Eva, Hassanein, Mahmoud, Hradec, Jaromir, Kavoliuniene, Ausra, Lainscak, Mitja, Logeart, Damien, Merkely, Bela, Metra, Marco, Persson, Hans, Seferovic, Petar, Temizhan, Ahmet, Tousoulis, Dimitris, Tavazzi, Luigi, Andarala, M., Fiorucci, E., Folkesson, E., Glemot, M., Gracia, G., Konte, M., Laroche, C., Mcneill, P. a., Missiamenou, V., Taylor, C., Fruhwald, F., Eberl, Alexander, Heller, S., Dolze, T., Platzer, V., Ablasser, K., Auer, J., Poelzl, G., Moertl, D., Podczeck Schweighofer, A., Reiter, S., Pravdic, D., Fazlibegovic, E., Muslibegovic, A., Vitlianova, K., Katova, T., Kotirkov, K., Petrov, I., Velikov, T., Kurteva, T., Gatzov, P., Kamenova, D., Antova, M., Tisheva, S., Sirakova, V., Krejci, J., Spinar, J., Mikolaskova, M., Krupicka, J., Malek, F., Hegarova, M., Pudil, R., Monhart, Z., Lazarova, M., Reda, A., Khairy, T., Farag, N., Saleh, A., Said, K., Abdel Hamid, M., Halawa, S., Ibrahim, B., Hanna, R., Hassanein, M., Sobhy, M., El Messiry, F., El Shazly, A. H., Elrakshy, Y., Aboleineen, W., Gouda, M., Youssef, A., Elbahry, A., Abdel, A., Ebeid, H., Nasr, G., Sobhy, H., Ashmawy, M., Lefol, C., Isnard, R., Hagege, A., Thevenin, S., Jondeau, G., Logeart, D., Codjia, R., Galinier, M., Bauer, F., Delahaye, F., Lamblin, N., Fertin, M., De Groote, P., Coisne, D., Le Marcis, V., Lequeux, B., J. F., Ly, Lotton, P., Donal, E., Le Moal, V., Basquin, A., Reynaud, A., Ridard, C., Thebault, C., Behar, N., Mascle, S., Schiele, F., Seronde, M. F., Morel, M., Meneveau, N., Luporsi, P., Bernard, Y., Pillot, M., Briand, F., Damy, T., Eicher, J. C., Avgeropoulou, C., Panagiotis, T., Tousoulis, D., Kotrogiannis, I., Stefanadis, C., Chrysohoou, C., Tsitsinakis, G., Dimitroula, T., Karavidas, A., Matzaraki, V., Terrovitis, J., Kapelios, C., Sfakianaki, T., Filippatos, G., Parissis, J. T., Ntai, K., Papadopoulou, A., Tziourganou, H., Douras, A., Ntertsas, K., Karotsaki, T., Nikoloulis, N., Tsaknakis, T., Patrianakos, A., Nyktari, E., Vardas, P., Soos, P., Nyolczas, N., Csaba Nagy, A., Halmosi, R., Nemeth, F., Amon, G., Dinnyes, J., Vazan Fuhrmann, A., Shotan, A., Alony, I., Elber, J., Olaru, A., Valenti, C., Reggianini, L., Modena, M. G., Copelli, S., Leuzzi, Concetta, Dei Cas, L., Carubelli, V., Lombardi, Cecilia, Bulgari, M., Tanghetti, E., Quinzani, F., Metra, M., Rovetta, R., Brasolin, B., Fedele, F., Sergi, Daniela, Romeo, F., Scarfò, I., Vellini, M., Fabris, E., Cinquetti, Martino, Stolfo, Davide, Sinagra, Gianfranco, Merlo, Marco, Fucili, A., Ferrari, R., Vassanelli, C., Torelli, F., Marchese, G., Zanolla, L., Cicoira, M., Anselmi, Manuel, Piccinino, C., Sartori, C., Di Ruocco, M. V., Marino, P. N., Giordano, A., Brognoli, S., Zanelli, E., Cosmi, F., Cadeddu, C., Bandino, S., Mercuro, G., Deidda, M., Salvemini, G., Correale, M., Di Biase, M., Musio, S., Passero, T., Italiano, Graziella, Agostoni, P., Salvioni, E., Schiavina, G., Squeri, CARLO ATTILIO, Bosi, S., Barbieri, A., Lemme, E., Penco, M., Marcon, S., Romano, S., Di Mauro, M., Frisinghelli, A., Veniani, M., Pieri, Pietro, Novo, S., Proclemer, Alessandro, Fresco, C., Miani, Daniela, Artico, Jessica, Gaita, F., Bergerone, S., Pirelli, SALVATORE DONATO, Di Tano, G., Cattaneo, Silvana, Gualco, A., Opasich, C., Priori, S. G., Iori, Elisa, Leci, E., Melandri, F., Voronina, N., Erglis, A., Kalnins, A., Kavoliuniene, A., Rumbinaite, E., Kazakauskaite, E., Petraskiene, I., Karaliute, R., Smalinskas, V., Tamakauskas, V., Petraskiene, D., Brazyte Ramanauskiene, R., Vysniauskas, V., Nowicka, A., Grabia, J., Dankowski, R., Szyszka, A., Szymanowska, K., Straburzynska Migaj, E., Kaluzna Oleksy, M., Grajek, S., Kasztelowicz, P., Orzel, T., Bednarczyk, G., Ruszkowski, P., Klimkiewicz, J., Majzner, A., Matusiak, A., Bylicka, E., Kwiatkowska, E., Kwiatkowska, K., Ochnio, M., Krzyzewska, T., Tarnowska, A., Komuda, K., Sobieszczanska Malek, M., Leszek, P., Rywik, T., Wisniewska, J., Kozar Kaminska, K., Piotrowska, M., Zielinski, T., Mamcarz, A., Welnicki, M., Folga, A., Kaplon Cieslicka, A., Opolski, G., Marchel, M., Balsam, P., Michalek, A., Pawlak, A., Byczkowska, K., Mozenska, O., Gil, K., Gil, R. J., Skrobowski, A., Uzieblo Zyczkowska, B., Piotrowicz, K., Krzesinski, P., Stanczyk, A., Ciurzynski, M., Bienias, P., Pruszczyk, P., Juszczyk, Z., Switala, P., Stankala, S., Polonski, L., Rozentryt, P., Gabryel, J., Lazorko Piega, M., Kardaszewicz, P., Poprawa, I., Komorowska, E., Lauko Rachocka, A., Abdulkarim, A. F., Dudzik Plocica, A., Zolbach, A., Sajnaga, D., Komorowska, K., Baczynska, K., Samcik, M., Wolniewicz, L., Wozakowska Kaplon, B., Sosnowska Pasiarska, B., Bartkowiak, R., Fiega, A., Serwicka, A., Szymczyk, A., Fitas, G., Zysko, D., Poliwczak, A., Broncel, M., Bala, A., Kasprzak, J. D., Jankowski, L., Rudzinska, M., Zycinski, P., Retwinski, A., Pietka, I., Drozdz, J., Wojtczak Soska, K., Jankowska, E., Ponikowski, P., Cichy, A., Kostka, A., Kaminski, L., Weglarz, J., Bodys, A., Flis, P., Kleinrok, A., Prokop Lewicka, G., Mosakowska, K., Rynkiewicz, A., Bellwon, J., Dabrowska Kugacka, A., Lewicka, E., Raczak, G., Skorek, E., Szabowski, S., Krysiak, W., Pietrzak, J., Gilewski, W., Sinkiewicz, W., Furman, A., Zalewski, J., Nessler, J., Bury, K., Grzegorzko, A., Zabojszcz, M., Mirek Bryniarska, E., Klys, J., Przybylska, K., Szulik, M., Kalarus, Z., Kuczaj, A., Nowalany Kozielska, E., Krzeminski, A., Ventosa, A., Tavares Aguiar, C., Moura, B., Cardoso, J. S., De Jesus, I., Chin, J., Faria, R., Pereira, S., Lima, Giuseppe, Oliveira Guimarães, T., Francisco, A. R., Brito, D., Placido, R., Martins, S., Fonseca, C., Marques, F., Araujo, I., Proenca, M., Cardiga, R., Andrade, A., Castro, Alessandra, Pereira, A., Queirós, C., Silva, P., Santos, R., Lourenço, C., Moreno, N., Almeida, F., Quelhas, I., Baptista, A., Ferreira, A., Magalhaes, P., Ferreira, Clara, Moreira, I., Durao, D., Severino, D., Ferreira Da Silva, G., Marta, L., Peres, Martina, Stanescu, C., Dan, A., Dan, G. A., Daha, I., Popescu, R., Vinereanu, D., Sinescu, C. J., Macarie, C., Radoi, M., Nechita, E., Christodorescu, R., Datcu, M., Craiu, E., Otasevic, P., Ristic, A. D., Simeunovic, D., Seferovic, P., Pencic, B., Andric, A., Stojcevski, B., Lebedinski, E., Suzic Lazic, J., Celic, V., Krotin, M., Radovanovic, Slavena, Iric Cupic, V., Milanov, S., Davidovic, G., Jovic, Masa, Radin, A., Mihajlovic, B., Stojiljkovic, J., Cankovic, M., Cemerlic Adic, N., Dodic, Sara, Kecojevic, S., Stojsic, S., Petrovic, D., Deljanin Ilic, M., Ilić, Saša, Stoickov, V., Antic, S., Stanojevic, D., Pavlovic, M., Atanaskovic, V., Mitic, Vanja, Kovar, F., Goncalvesova, E., Murin, J., Pernicky, M., Klabnik, A., Kmec, J., Rajtman, D., Kovac, D., Horvat, Sara, Krunic, B., Bombek, M., Krajnc, I., Losic, R., Glavic, T., Komel, Janja, Cernic Suligoj, N., Ravnikar, T., Letonja, M., Cencic, Vanja, Savnik Iskra, M., Strasek, M., Leskovar, B., Drnovsek, B., Klen, J., Marolt, A., Kladnik, M., Slemenik Pusnik, C., Pusnik Vrckovnik, M., Jug, Barbara, Fras, Z., Bartolic, Andrej, Melihen Bartolic, C., Valentincic, M., Winkler, R., Blanco Canosa, P., Grille Cancela, Z., Crespo Leiro, M., Paniagua Martin, M. 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R., Brito, D., Placido, R., Martins, S., Fonseca, C., Marques, F., Araujo, I., Proenca, M., Cardiga, R., Andrade, A., Castro, Alessandra, Pereira, A., Queirós, C., Silva, P., Santos, R., Lourenço, C., Moreno, N., Almeida, F., Quelhas, I., Baptista, A., Ferreira, A., Magalhaes, P., Ferreira, Clara, Moreira, I., Durao, D., Severino, D., Ferreira Da Silva, G., Marta, L., Peres, Martina, Stanescu, C., Dan, A., Dan, G. A., Daha, I., Popescu, R., Vinereanu, D., Sinescu, C. J., Macarie, C., Radoi, M., Nechita, E., Christodorescu, R., Datcu, M., Craiu, E., Otasevic, P., Ristic, A. D., Simeunovic, D., Seferovic, P., Pencic, B., Andric, A., Stojcevski, B., Lebedinski, E., Suzic Lazic, J., Celic, V., Krotin, M., Radovanovic, Slavena, Iric Cupic, V., Milanov, S., Davidovic, G., Jovic, Masa, Radin, A., Mihajlovic, B., Stojiljkovic, J., Cankovic, M., Cemerlic Adic, N., Dodic, Sara, Kecojevic, S., Stojsic, S., Petrovic, D., Deljanin Ilic, M., Ilić, Saša, Stoickov, V., Antic, S., Stanojevic, D., Pavlovic, M., Atanaskovic, V., Mitic, Vanja, Kovar, F., Goncalvesova, E., Murin, J., Pernicky, M., Klabnik, A., Kmec, J., Rajtman, D., Kovac, D., Horvat, Sara, Krunic, B., Bombek, M., Krajnc, I., Losic, R., Glavic, T., Komel, Janja, Cernic Suligoj, N., Ravnikar, T., Letonja, M., Cencic, Vanja, Savnik Iskra, M., Strasek, M., Leskovar, B., Drnovsek, B., Klen, J., Marolt, A., Kladnik, M., Slemenik Pusnik, C., Pusnik Vrckovnik, M., Jug, Barbara, Fras, Z., Bartolic, Andrej, Melihen Bartolic, C., Valentincic, M., Winkler, R., Blanco Canosa, P., Grille Cancela, Z., Crespo Leiro, M., Paniagua Martin, M. J., Marzoa Rivas, R., Barge Caballero, E., Torres Calvo, F., Bravo Marques, R., Epelde Gonzalo, F., Recio Platero, A., De La Fuente Galan, L., Lopez Diaz, J., Goncalvez Ramirez, L. Renier, Cubero Gallego, H., Sliwiski Herrera, J. F., Bierge Valero, D., Salmeron, F. M., Gallego Page, J. C., Jose Fernandez, M., Sahuquillo, A., Garcia De La Villa, B., Castro Conde, A., Iniesta Manjavacas, A. M., Salvador Montanes, O., Gonzalez Gallarza, R. Dalmau, Ofelia Rosillo, S., Araujo, A., Briceno, A., Alonso Pulpon, L., Cobo, M., Soria, T., Gomez Bueno, M., Garcia Pavia, P., Gonzalez Segovia, A., Sayago, I., Segovia Cubero, J., Delgado Jiménez, J. F., Angel Gomez Sanchez, M., Escribano Subias, P., Barrios Garrido Lestache, E., Ruiz Cano, M. J., Vicente Hernandez, M., Puga Martinez, M., Lopez Moreno, E., Serrano Martinez, J. L., Fernandez Alvarez, M., Rivera Lopez, R., Lopez Fernandez, S., Alcade Martinez, V., Sanmartin, M., Pellicer Cabo, A., Garcia Escriva, D., Ridocci Soriano, F., Perez Silvestre, J., Facila Rubio, L., Garcia Gonzalez, P., Sanchez Lazaro, I. J., Almenar Bonet, L., Garcia Pinilla, J. M., Andres, Ulrike Julia, Bayes Genis, A., Roig, E., Mirabet, S., Mendez, A., Garcia Cosio, L., Garay, A., Muntane, G., Gonzalez Costello, J., Leon, V., Diaz Molina, B., Famara Hernandez, I., Lara Padron, A., Laynez Cerdena, I., Mateo, I., Quiles, J., Bertomeu, V., Elamrani, A., Angel Rodrigez Ortega, J., Martinez Abellan, R., Valero, R., Fernandez Vivancos, C., Sanz Julve, M., Perez Martinez, M. T., Pascual Figal, D. A., Martinez Martinez Espejo, M. D., Rosario Gracia Rodenas, M., Pastor Perez, F., Melin, M., Hägglund, E., Stenberg, A., Lindahl, I. M., Asserlund, B., Olsson, L., Dahlström, U., Afzelius, M., Karlström, P., Tengvall, L., Wiklund, P. A., Olsson, B., Temizhan, A., Kalayci, S., Bozkurt, M., Taraktas, M., Cavusoglu, Y., Gunes, H., Birhan Yilmaz, M., Demir, B., and Gencer, E.
Subjects: Registrie, Male, ACE inhibitors, Angiotensin-Converting Enzyme Inhibitors, Nitrate, Beta-blockers, Ambulatory Care, Medicine, Registries, Diuretics, Mineralocorticoid Receptor Antagonists, Angiotensin Receptor Antagonist, Middle Aged, Defibrillators, Implantable, Clinical Practice, Europe, Hospitalization, Ambulatory, MRAs, Practice Guidelines as Topic, MRA, Cardiology, CRT, Female, Guideline Adherence, Implantable, Cardiology and Cardiovascular Medicine, Human, medicine.medical_specialty, Cardiotonic Agents, cardiology and cardiovascular mediciney, Mineralocorticoid Antagonists, Adrenergic beta-Antagonists, Heart failure, ICD, Aged, Angiotensin Receptor Antagonists, Heart Failure, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Nitrates, Platelet Aggregation Inhibitors, Drug treatment, ACE inhibitor, Internal medicine, Diuretic, Cardiotonic Agent, In patient, Beta-blocker, Mineralocorticoid Receptor Antagonist, business.industry, Platelet Aggregation Inhibitor, beta-blockers, heart failure, adrenergic beta-antagonists, aged, ambulatory care, angiotensin receptor antagonists, angiotensin-converting enzyme inhibitors, cardiology, cardiotonic agents, defibrillators, implantable, diuretics, europe, female, guideline adherence, hospitalization, humans, hydroxymethylglutaryl-coa reductase inhibitors, male, middle aged, mineralocorticoid receptor antagonists, nitrates, platelet aggregation inhibitors, practice guidelines as topic, registries, Adrenergic beta-Antagonist, Angiotensin-Converting Enzyme Inhibitor, Guideline, medicine.disease, Observational study, Hydroxymethylglutaryl-CoA Reductase Inhibitor, business, Defibrillators
Abstract: AimsTo evaluate how recommendations of European guidelines regarding pharmacological and non-pharmacological treatments for heart failure (HF) are adopted in clinical practice.Methods and resultsThe ESC-HF Long-Term Registry is a prospective, observational study conducted in 211 Cardiology Centres of 21 European and Mediterranean countries, members of the European Society of Cardiology (ESC). From May 2011 to April 2013, a total of 12 440 patients were enrolled, 40.5% with acute HF and 59.5% with chronic HF. Intravenous treatments for acute HF were heterogeneously administered, irrespective of guideline recommendations. In chronic HF, with reduced EF, renin-angiotensin system (RAS) blockers, beta-blockers, and mineralocorticoid antagonists (MRAs) were used in 92.2, 92.7, and 67.0% of patients, respectively. When reasons for non-adherence were considered, the real rate of undertreatment accounted for 3.2, 2.3, and 5.4% of the cases, respectively. About 30% of patients received the target dosage of these drugs, but a documented reason for not achieving the target dosage was reported in almost two-thirds of them. The more relevant reasons for non-implantation of a device, when clinically indicated, were related to doctor uncertainties on the indication, patient refusal, or logistical/cost issues.ConclusionThis pan-European registry shows that, while in patients with acute HF, a large heterogeneity of treatments exists, drug treatment of chronic HF can be considered largely adherent to recommendations of current guidelines, when the reasons for non-adherence are taken into account. Observations regarding the real possibility to adhere fully to current guidelines in daily clinical practice should be seriously considered when clinical practice guidelines have to be written. © 2013 Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2013. For permissions please email: journals.permissions@oup.com
Published: 2013

15. An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers.

Author: Blein, S., Bardel, C., Danjean, V., McGuffog, L., Healey, S., Barrowdale, D., Lee, A., Dennis, J., Kuchenbaecker, K.B., Soucy, P., Terry, M.B., Chung, W.K., Goldgar, D.E., Buys, S.S., Janavicius, R., Tihomirova, L., Tung, N., Dorfling, C.M., Rensburg, E.J. van, Neuhausen, S.L., Ding, Y.C., Gerdes, A.M., Ejlertsen, B., Nielsen, F.C., Hansen, T.V., Osorio, A., Benitez, J., Conejero, R.A., Segota, E., Weitzel, J.N., Thelander, M., Peterlongo, P., Radice, P., Pensotti, V., Dolcetti, R., Bonanni, B., Peissel, B., Zaffaroni, D., Scuvera, G., Manoukian, S., Varesco, L., Capone, G.L., Papi, L., Ottini, L., Yannoukakos, D., Konstantopoulou, I., Garber, J., Hamann, U., Donaldson, A., Brady, A., Brewer, C., Foo, C., Evans, D.G., Frost, D., Eccles, D., Douglas, F., Cook, J., Adlard, J., Barwell, J., Walker, L., Izatt, L., Side, L.E., Kennedy, M.J., Tischkowitz, M., Rogers, M.T., Porteous, M.E., Morrison, P.J., Platte, R., Eeles, R., Davidson, R., Hodgson, S., Cole, T., Godwin, A.K., Isaacs, C., Claes, K., Leeneer, K. De, Meindl, A., Gehrig, A., Wappenschmidt, B., Sutter, C., Engel, C., Niederacher, D., Steinemann, D., Plendl, H., Kast, K., Rhiem, K., Ditsch, N., Arnold, N., Varon-Mateeva, R., Schmutzler, R.K., Preisler-Adams, S., Markov, N.B., Wang-Gohrke, S., Pauw, A. de, Lefol, C., Lasset, C., Leroux, D., Rouleau, E., Damiola, F., Dreyfus, H., Barjhoux, L., Golmard, L., Uhrhammer, N., Bonadona, V., Sornin, V., Bignon, Y.J., Carter, J., Le, L, Piedmonte, M., DiSilvestro, P.A., Hoya, M. de la, Caldes, T., Nevanlinna, H., Aittomaki, K., Jager, A., Ouweland, A.M. van den, Kets, C.M., Aalfs, C.M., Leeuwen, F.E. van, Hogervorst, F.B., Meijers-Heijboer, H.E., Oosterwijk, J.C., Roozendaal, K.E. van, Rookus, M.A., Devilee, P., Luijt, R.B. van der, Olah, E., Diez, O., Teule, A., Lazaro, C., Blanco, I., Valle, J., Jakubowska, A., Sukiennicki, G., Gronwald, J., Lubinski, J., Durda, K., Jaworska-Bieniek, K., Agnarsson, B.A., Maugard, C., Amadori, A., Montagna, M., Teixeira, M.R., Spurdle, A.B., Foulkes, W., Olswold, C., Lindor, N.M., Pankratz, V.S., Szabo, C.I., Lincoln, A., Jacobs, L., Corines, M., Robson, M., Vijai, J., Berger, A., Fink-Retter, A., Singer, C.F., Rappaport, C., Kaulich, D.G., Pfeiler, G., Tea, M.K., Greene, M.H., Mai, P.L., Rennert, G., Imyanitov, E.N., Mulligan, A.M., Glendon, G., Andrulis, I.L., Tchatchou, S., Toland, A.E., Pedersen, I.S., Thomassen, M., Kruse, T.A., Jensen, U.B., Caligo, M.A., Friedman, E., Zidan, J., Laitman, Y., Lindblom, A., Melin, B., Arver, B., Loman, N., Rosenquist, R., Olopade, O.I., Nussbaum, R.L., Ramus, S.J., Nathanson, K.L., Domchek, S.M., Rebbeck, T.R., Arun, B.K., Mitchell, G., Karlan, B.Y., Lester, J., Orsulic, S., Stoppa-Lyonnet, D., Thomas, G, Simard, J., Couch, F.J., Offit, K., Easton, D.F., Chenevix-Trench, G., Antoniou, A.C., Mazoyer, S., Phelan, C.M., Sinilnikova, O.M., Cox, D.G., Blein, S., Bardel, C., Danjean, V., McGuffog, L., Healey, S., Barrowdale, D., Lee, A., Dennis, J., Kuchenbaecker, K.B., Soucy, P., Terry, M.B., Chung, W.K., Goldgar, D.E., Buys, S.S., Janavicius, R., Tihomirova, L., Tung, N., Dorfling, C.M., Rensburg, E.J. van, Neuhausen, S.L., Ding, Y.C., Gerdes, A.M., Ejlertsen, B., Nielsen, F.C., Hansen, T.V., Osorio, A., Benitez, J., Conejero, R.A., Segota, E., Weitzel, J.N., Thelander, M., Peterlongo, P., Radice, P., Pensotti, V., Dolcetti, R., Bonanni, B., Peissel, B., Zaffaroni, D., Scuvera, G., Manoukian, S., Varesco, L., Capone, G.L., Papi, L., Ottini, L., Yannoukakos, D., Konstantopoulou, I., Garber, J., Hamann, U., Donaldson, A., Brady, A., Brewer, C., Foo, C., Evans, D.G., Frost, D., Eccles, D., Douglas, F., Cook, J., Adlard, J., Barwell, J., Walker, L., Izatt, L., Side, L.E., Kennedy, M.J., Tischkowitz, M., Rogers, M.T., Porteous, M.E., Morrison, P.J., Platte, R., Eeles, R., Davidson, R., Hodgson, S., Cole, T., Godwin, A.K., Isaacs, C., Claes, K., Leeneer, K. De, Meindl, A., Gehrig, A., Wappenschmidt, B., Sutter, C., Engel, C., Niederacher, D., Steinemann, D., Plendl, H., Kast, K., Rhiem, K., Ditsch, N., Arnold, N., Varon-Mateeva, R., Schmutzler, R.K., Preisler-Adams, S., Markov, N.B., Wang-Gohrke, S., Pauw, A. de, Lefol, C., Lasset, C., Leroux, D., Rouleau, E., Damiola, F., Dreyfus, H., Barjhoux, L., Golmard, L., Uhrhammer, N., Bonadona, V., Sornin, V., Bignon, Y.J., Carter, J., Le, L, Piedmonte, M., DiSilvestro, P.A., Hoya, M. de la, Caldes, T., Nevanlinna, H., Aittomaki, K., Jager, A., Ouweland, A.M. van den, Kets, C.M., Aalfs, C.M., Leeuwen, F.E. van, Hogervorst, F.B., Meijers-Heijboer, H.E., Oosterwijk, J.C., Roozendaal, K.E. van, Rookus, M.A., Devilee, P., Luijt, R.B. van der, Olah, E., Diez, O., Teule, A., Lazaro, C., Blanco, I., Valle, J., Jakubowska, A., Sukiennicki, G., Gronwald, J., Lubinski, J., Durda, K., Jaworska-Bieniek, K., Agnarsson, B.A., Maugard, C., Amadori, A., Montagna, M., Teixeira, M.R., Spurdle, A.B., Foulkes, W., Olswold, C., Lindor, N.M., Pankratz, V.S., Szabo, C.I., Lincoln, A., Jacobs, L., Corines, M., Robson, M., Vijai, J., Berger, A., Fink-Retter, A., Singer, C.F., Rappaport, C., Kaulich, D.G., Pfeiler, G., Tea, M.K., Greene, M.H., Mai, P.L., Rennert, G., Imyanitov, E.N., Mulligan, A.M., Glendon, G., Andrulis, I.L., Tchatchou, S., Toland, A.E., Pedersen, I.S., Thomassen, M., Kruse, T.A., Jensen, U.B., Caligo, M.A., Friedman, E., Zidan, J., Laitman, Y., Lindblom, A., Melin, B., Arver, B., Loman, N., Rosenquist, R., Olopade, O.I., Nussbaum, R.L., Ramus, S.J., Nathanson, K.L., Domchek, S.M., Rebbeck, T.R., Arun, B.K., Mitchell, G., Karlan, B.Y., Lester, J., Orsulic, S., Stoppa-Lyonnet, D., Thomas, G, Simard, J., Couch, F.J., Offit, K., Easton, D.F., Chenevix-Trench, G., Antoniou, A.C., Mazoyer, S., Phelan, C.M., Sinilnikova, O.M., and Cox, D.G.
Abstract: Contains fulltext : 156875.pdf (publisher's version ) (Open Access), INTRODUCTION: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. METHODS: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. RESULTS: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. CONCLUSIONS: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effe
Published: 2015

16. An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Author: Blein, S. (Sophie), Bardel, C. (Claire), Danjean, V. (Vincent), McGuffog, L. (Lesley), Healey, S. (Sue), Barrowdale, D. (Daniel), Lee, A. (Andrew), Dennis, J. (Joe), Kuchenbaecker, K.B. (Karoline), Soucy, P. (Penny), Terry, M.B. (Mary Beth), Chung, W. (Wendy), Goldgar, D. (David), Buys, S.S. (Saundra), Janavicius, R. (Ramunas), Tihomirova, L. (Laima), Tung, N. (Nadine), Dorfling, C.M. (Cecilia), Rensburg, E.J. (Elizabeth) van, Neuhausen, S.L. (Susan), Ding, Y.C. (Yuan), Gerdes, A-M. (Anne-Marie), Ejlertsen, B. (Bent), Nielsen, F. (Finn), Hansen, T.V.O. (Thomas), Osorio, A. (Ana), Benítez, J. (Javier), Conejero, R.A. (Raquel Andrés), Segota, E. (Ena), Weitzel, J.N. (Jeffrey), Thelander, M. (Margo), Peterlongo, P. (Paolo), Radice, P. (Paolo), Pensotti, V. (Valeria), Dolcetti, R. (Riccardo), Bonnani, B. (Bernardo), Peissel, B. (Bernard), Zaffaroni, D. (D.), Scuvera, G. (Giulietta), Manoukian, S. (Siranoush), Varesco, L. (Liliana), Capone, G.L. (Gabriele L.), Papi, L. (Laura), Ottini, L. (Laura), Yannoukakos, D. (Drakoulis), Konstantopoulou, I. (I.), Garber, J. (Judy), Hamann, U. (Ute), Donaldson, A. (Alan), Brady, A. (A.), Brewer, C. (Carole), Foo, C. (Claire), Evans, D.G. (Gareth), Frost, D. (Debra), Eccles, D. (Diana), Douglas, F. (Fiona), Cook, J. (Jackie), Adlard, L., Barwell, J. (Julian), Walker, L.J. (Lisa), Izatt, L. (Louise), Side, L. (Lucy), Kennedy, M.J. (John), Tischkowitz, M. (Marc), Rogers, M.T. (Mark), Porteous, M.E. (Mary), Morrison, P.J. (Patrick), Platte, R. (Radka), Eeles, R. (Ros), Davidson, R. (Rosemarie), Hodgson, S. (Shirley), Cole, T.J. (Trevor), Godwin, A.K. (Andrew), Isaacs, C. (Claudine), Claes, K.B.M. (Kathleen B.M.), De Leeneer, K. (Kim), Meindl, A. (Alfons), Gehrig, P.A. (Paola A.), Wapenschmidt, B. (Barbara), Sutter, C. (Christian), Engel, C. (Christoph), Niederacher, D. (Dieter), Steinemann, D. (Doris), Plendl, H. (Hansjoerg), Kast, K. (Karin), Rhiem, K. (Kerstin), Ditsch, N. (Nina), Arnold, N. (Norbert), Varon-Mateeva, R. (Raymonda), Schmutzler, R.K. (Rita), Preisler-Adams, S. (Sabine), Markov, N.B. (Nadja Bogdanova), Wang-Gohrke, S. (Shan), Pauw, A. (Antoine) de, Lefol, C. (Cédrick), Lasset, C. (Christine), Leroux, D. (Dominique), Rouleau, E. (Etienne), Damiola, F. (Francesca), Dreyfus, H. (Hélène), Barjhoux, L. (Laure), Golmard, L. (Lisa), Uhrhammer, N. (Nancy), Bonadona, V. (Valérie), Sornin, V. (Valérie), Bignon, Y.-J. (Yves-Jean), Carter, J. (Jonathan), Le, L. (Linda) van, Piedmonte, M. (Marion), DiSilvestro, P. (Paul), Hoya, M. (Miguel) de La, Caldes, T. (Trinidad), Nevanlinna, H. (Heli), Aittomäki, K. (Kristiina), Jager, A. (Agnes), Ouweland, A.M.W. (Ans) van den, Kets, C.M. (Marleen), Aalfs, C.M. (Cora), Leeuwen, F.E. (Flora) van, Hogervorst, F.B.L. (Frans), Meijers-Heijboer, E.J. (Hanne), Oosterwijk, J.C. (Jan), Roozendaal, K.E. (Kees) van, Rookus, M.A. (M.), Devilee, P. (Peter), Luijt, R.B. (Rob) van der, Olah, E., Díez, O. (Orland), Teulé, A. (A.), Lázaro, C. (Conxi), Blanco, I. (Ignacio), Del Valle, J. (Jesús), Jakubowska, A. (Anna), Sukiennicki, G. (Grzegorz), Gronwald, J. (Jacek), Lubinski, J. (Jan), Durda, K. (Katarzyna), Jaworska-Bieniek, K. (Katarzyna), Agnarsson, B.A. (Bjarni), Maugard, C., Amadori, A. (Alberto), Montagna, M. (Marco), Teixeira, P.J., Spurdle, A.B. (Amanda), Foulkes, W.D. (William), Olswold, C. (Curtis), Lindor, N.M. (Noralane), Pankratz, V.S. (Shane), Szabo, C. (Csilla), Lincoln, A. (Anne), Jacobs, L. (Lauren), Corines, M. (Marina), Robson, M. (Mark), Vijai, J. (Joseph), Berger, A. (Andreas), Fink-Retter, A. (Anneliese), Singer, C.F. (Christian), Rappaport, C. (Christine), Kaulich, D.G. (Daphne Gschwantler), Pfeiler, G. (Georg), Tea, M.-K., Greene, M.H. (Mark), Mai, P.L. (Phuong), Rennert, G. (Gad), Imyanitov, E.N. (Evgeny), Mulligan, A.M. (Anna Marie), Glendon, G. (Gord), Andrulis, I.L. (Irene), Tchatchou, S. (Sandrine), Toland, A.E. (Amanda), Pedersen, I.S. (Inge Sokilde), Thomassen, M. (Mads), Kruse, T.A. (Torben), Jensen, U.B., Caligo, M.A. (Maria), Friedman, E. (Eitan), Zidan, J. (Jamal), Laitman, Y. (Yael), Lindblom, A. (Annika), Melin, B. (Beatrice), Arver, B. (Brita Wasteson), Loman, N. (Niklas), Rosenquist, R. (R.), Olopade, O.I. (Olofunmilayo), Nussbaum, R. (Robert), Ramus, S.J. (Susan), Nathanson, K.L. (Katherine), Domchek, S.M. (Susan), Rebbeck, R. (Timothy), Arun, B.K. (Banu), Mitchell, G. (Gillian), Karlan, B.Y. (Beth), Lester, K.J. (Kathryn), Orsulic, S. (Sandra), Stoppa-Lyonnet, D. (Dominique), Thomas, G. (Gilles), Simard, J. (Jacques), Couch, F.J. (Fergus), Offit, K. (Kenneth), Easton, D.F. (Douglas), Chenevix-Trench, G. (Georgia), Antoniou, A.C. (Antonis), Mazoyer, S. (Sylvie), Phelan, C. (Catherine), Sinilnikova, O. (Olga), Cox, D.G. (David), Blein, S. (Sophie), Bardel, C. (Claire), Danjean, V. (Vincent), McGuffog, L. (Lesley), Healey, S. (Sue), Barrowdale, D. (Daniel), Lee, A. (Andrew), Dennis, J. (Joe), Kuchenbaecker, K.B. (Karoline), Soucy, P. (Penny), Terry, M.B. (Mary Beth), Chung, W. (Wendy), Goldgar, D. (David), Buys, S.S. (Saundra), Janavicius, R. (Ramunas), Tihomirova, L. (Laima), Tung, N. (Nadine), Dorfling, C.M. (Cecilia), Rensburg, E.J. (Elizabeth) van, Neuhausen, S.L. (Susan), Ding, Y.C. (Yuan), Gerdes, A-M. (Anne-Marie), Ejlertsen, B. (Bent), Nielsen, F. (Finn), Hansen, T.V.O. (Thomas), Osorio, A. (Ana), Benítez, J. (Javier), Conejero, R.A. (Raquel Andrés), Segota, E. (Ena), Weitzel, J.N. (Jeffrey), Thelander, M. (Margo), Peterlongo, P. (Paolo), Radice, P. (Paolo), Pensotti, V. (Valeria), Dolcetti, R. (Riccardo), Bonnani, B. (Bernardo), Peissel, B. (Bernard), Zaffaroni, D. (D.), Scuvera, G. (Giulietta), Manoukian, S. (Siranoush), Varesco, L. (Liliana), Capone, G.L. (Gabriele L.), Papi, L. (Laura), Ottini, L. (Laura), Yannoukakos, D. (Drakoulis), Konstantopoulou, I. (I.), Garber, J. (Judy), Hamann, U. (Ute), Donaldson, A. (Alan), Brady, A. (A.), Brewer, C. (Carole), Foo, C. (Claire), Evans, D.G. (Gareth), Frost, D. (Debra), Eccles, D. (Diana), Douglas, F. (Fiona), Cook, J. (Jackie), Adlard, L., Barwell, J. (Julian), Walker, L.J. (Lisa), Izatt, L. (Louise), Side, L. (Lucy), Kennedy, M.J. (John), Tischkowitz, M. (Marc), Rogers, M.T. (Mark), Porteous, M.E. (Mary), Morrison, P.J. (Patrick), Platte, R. (Radka), Eeles, R. (Ros), Davidson, R. (Rosemarie), Hodgson, S. (Shirley), Cole, T.J. (Trevor), Godwin, A.K. (Andrew), Isaacs, C. (Claudine), Claes, K.B.M. (Kathleen B.M.), De Leeneer, K. (Kim), Meindl, A. (Alfons), Gehrig, P.A. (Paola A.), Wapenschmidt, B. (Barbara), Sutter, C. (Christian), Engel, C. (Christoph), Niederacher, D. (Dieter), Steinemann, D. (Doris), Plendl, H. (Hansjoerg), Kast, K. (Karin), Rhiem, K. (Kerstin), Ditsch, N. (Nina), Arnold, N. (Norbert), Varon-Mateeva, R. (Raymonda), Schmutzler, R.K. (Rita), Preisler-Adams, S. (Sabine), Markov, N.B. (Nadja Bogdanova), Wang-Gohrke, S. (Shan), Pauw, A. (Antoine) de, Lefol, C. (Cédrick), Lasset, C. (Christine), Leroux, D. (Dominique), Rouleau, E. (Etienne), Damiola, F. (Francesca), Dreyfus, H. (Hélène), Barjhoux, L. (Laure), Golmard, L. (Lisa), Uhrhammer, N. (Nancy), Bonadona, V. (Valérie), Sornin, V. (Valérie), Bignon, Y.-J. (Yves-Jean), Carter, J. (Jonathan), Le, L. (Linda) van, Piedmonte, M. (Marion), DiSilvestro, P. (Paul), Hoya, M. (Miguel) de La, Caldes, T. (Trinidad), Nevanlinna, H. (Heli), Aittomäki, K. (Kristiina), Jager, A. (Agnes), Ouweland, A.M.W. (Ans) van den, Kets, C.M. (Marleen), Aalfs, C.M. (Cora), Leeuwen, F.E. (Flora) van, Hogervorst, F.B.L. (Frans), Meijers-Heijboer, E.J. (Hanne), Oosterwijk, J.C. (Jan), Roozendaal, K.E. (Kees) van, Rookus, M.A. (M.), Devilee, P. (Peter), Luijt, R.B. (Rob) van der, Olah, E., Díez, O. (Orland), Teulé, A. (A.), Lázaro, C. (Conxi), Blanco, I. (Ignacio), Del Valle, J. (Jesús), Jakubowska, A. (Anna), Sukiennicki, G. (Grzegorz), Gronwald, J. (Jacek), Lubinski, J. (Jan), Durda, K. (Katarzyna), Jaworska-Bieniek, K. (Katarzyna), Agnarsson, B.A. (Bjarni), Maugard, C., Amadori, A. (Alberto), Montagna, M. (Marco), Teixeira, P.J., Spurdle, A.B. (Amanda), Foulkes, W.D. (William), Olswold, C. (Curtis), Lindor, N.M. (Noralane), Pankratz, V.S. (Shane), Szabo, C. (Csilla), Lincoln, A. (Anne), Jacobs, L. (Lauren), Corines, M. (Marina), Robson, M. (Mark), Vijai, J. (Joseph), Berger, A. (Andreas), Fink-Retter, A. (Anneliese), Singer, C.F. (Christian), Rappaport, C. (Christine), Kaulich, D.G. (Daphne Gschwantler), Pfeiler, G. (Georg), Tea, M.-K., Greene, M.H. (Mark), Mai, P.L. (Phuong), Rennert, G. (Gad), Imyanitov, E.N. (Evgeny), Mulligan, A.M. (Anna Marie), Glendon, G. (Gord), Andrulis, I.L. (Irene), Tchatchou, S. (Sandrine), Toland, A.E. (Amanda), Pedersen, I.S. (Inge Sokilde), Thomassen, M. (Mads), Kruse, T.A. (Torben), Jensen, U.B., Caligo, M.A. (Maria), Friedman, E. (Eitan), Zidan, J. (Jamal), Laitman, Y. (Yael), Lindblom, A. (Annika), Melin, B. (Beatrice), Arver, B. (Brita Wasteson), Loman, N. (Niklas), Rosenquist, R. (R.), Olopade, O.I. (Olofunmilayo), Nussbaum, R. (Robert), Ramus, S.J. (Susan), Nathanson, K.L. (Katherine), Domchek, S.M. (Susan), Rebbeck, R. (Timothy), Arun, B.K. (Banu), Mitchell, G. (Gillian), Karlan, B.Y. (Beth), Lester, K.J. (Kathryn), Orsulic, S. (Sandra), Stoppa-Lyonnet, D. (Dominique), Thomas, G. (Gilles), Simard, J. (Jacques), Couch, F.J. (Fergus), Offit, K. (Kenneth), Easton, D.F. (Douglas), Chenevix-Trench, G. (Georgia), Antoniou, A.C. (Antonis), Mazoyer, S. (Sylvie), Phelan, C. (Catherine), Sinilnikova, O. (Olga), and Cox, D.G. (David)
Abstract: Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusion
Published: 2015
Full Text: View/download PDF

17. Breast and ovarian cancer predisposition due to de novo BRCA1 and BRCA2 mutations

Author: Golmard, L, primary, Delnatte, C, additional, Laugé, A, additional, Moncoutier, V, additional, Lefol, C, additional, Abidallah, K, additional, Tenreiro, H, additional, Copigny, F, additional, Giraudeau, M, additional, Guy, C, additional, Barbaroux, C, additional, Amorim, G, additional, Briaux, A, additional, Guibert, V, additional, Tarabeux, J, additional, Caputo, S, additional, Collet, A, additional, Gesta, P, additional, Ingster, O, additional, Stern, M-H, additional, Rouleau, E, additional, de Pauw, A, additional, Gauthier-Villars, M, additional, Buecher, B, additional, Bézieau, S, additional, Stoppa-Lyonnet, D, additional, and Houdayer, C, additional
Published: 2015
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18. Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

Author: Kuchenbaecker, K.B. (Karoline), Neuhausen, S.L. (Susan), Robson, M. (Mark), Barrowdale, D. (Daniel), McGuffog, L. (Lesley), Mulligan, A.M. (Anna Marie), Andrulis, I.L. (Irene), Spurdle, A.B. (Amanda), Schmidt, M.K. (Marjanka), Schmutzler, R.K. (Rita), Engel, C. (Christoph), Wapenschmidt, B. (Barbara), Nevanlinna, H. (Heli), Thomassen, M. (Mads), Southey, M.C. (Melissa), Radice, P. (Paolo), Ramus, S.J. (Susan), Domchek, S.M. (Susan), Nathanson, K.L. (Katherine), Lee, A. (Andrew), Healey, S. (Sue), Nussbaum, R. (Robert), Rebbeck, R. (Timothy), Arun, B.K. (Banu), James, M. (Margaret), Karlan, B.Y. (Beth), Lester, K.J. (Kathryn), Cass, I. (Ilana), Terry, M.B. (Mary Beth), Daly, M.J. (Mark), Goldgar, D. (David), Buys, S.S. (Saundra), Janavicius, R. (Ramunas), Tihomirova, L. (Laima), Tung, N. (Nadine), Dorfling, C.M. (Cecilia), Rensburg, E.J. (Elizabeth) van, Steele, L. (Linda), Overeem Hansen, T. (Thomas) van, Ejlertsen, B. (Bent), Gerdes, A-M. (Anne-Marie), Nielsen, F. (Finn), Dennis, J. (Joe), Cunningham, J.M. (Julie), Hart, S. (Stewart), Slager, S. (Susan), Osorio, A. (Ana), Benítez, J. (Javier), Duran, M. (Mercedes), Weitzel, J.N. (Jeffrey), Tafur, I. (Isaac), Hander, M. (Mary), Peterlongo, P. (Paolo), Manoukian, S. (Siranoush), Peissel, B. (Bernard), Roversi, G. (Gaia), Scuvera, G. (Giulietta), Bonnani, B. (Bernardo), Mariani, P. (Paolo), Volorio, S. (Sara), Dolcetti, R. (Riccardo), Varesco, L. (Liliana), Papi, L. (Laura), Tibiletti, M.G. (Maria Grazia), Giannini, G. (Giuseppe), Fostira, F. (Florentia), Konstantopoulou, I. (I.), Garber, J. (Judy), Hamann, U. (Ute), Donaldson, A. (Alan), Brewer, C. (Carole), Foo, C. (Claire), Evans, D.G. (Gareth), Frost, D. (Debra), Eccles, D. (Diana), Douglas, F. (Fiona), Brady, A. (A.), Cook, J. (Jackie), Tischkowitz, M. (Marc), Adlard, L., Barwell, J. (Julian), Ong, K., Walker, L.J. (Lisa), Izatt, L. (Louise), Side, L. (Lucy), Kennedy, M.J. (John), Rogers, M.T. (Mark), Porteous, M.E. (Mary), Morrison, P.J. (Patrick), Platte, R. (Radka), Eeles, R. (Ros), Davidson, R. (Rosemarie), Hodgson, S. (Shirley), Ellis, S.D. (Steve), Godwin, A.K. (Andrew), Rhiem, K. (Kerstin), Meindl, A. (Alfons), Ditsch, N. (Nina), Arnold, N. (Norbert), Plendl, H. (Hansjoerg), Niederacher, D. (Dieter), Sutter, C. (Christian), Steinemann, D. (Doris), Bogdanova-Markov, N. (Nadja), Kast, K. (Karin), Varon-Mateeva, R. (Raymonda), Wang-Gohrke, S. (Shan), Gehrig, P.A. (Paola A.), Markiefka, B. (Birgid), Buecher, B. (Bruno), Lefol, C. (Cédrick), Stoppa-Lyonnet, D. (Dominique), Rouleau, E. (Etienne), Prieur, F. (Fabienne), Damiola, F. (Francesca), Barjhoux, L. (Laure), Faivre, L. (Laurence), Longy, M. (Michel), Sevenet, N. (Nicolas), Sinilnikova, O. (Olga), Mazoyer, S. (Sylvie), Bonadona, V. (Valérie), Caux-Moncoutier, V. (Virginie), Isaacs, C. (Claudine), Van Maerken, T. (Tom), Claes, K.B.M. (Kathleen B.M.), Piedmonte, M. (Marion), Andrews, L. (Lesley), Hays, J. (John), Rodriguez, G.C. (Gustavo), Caldes, T. (Trinidad), Hoya, M. (Miguel) de La, Khan, S. (Sofia), Hogervorst, F.B.L. (Frans), Aalfs, C.M. (Cora), Lange, J.L. (J.) de, Meijers-Heijboer, E.J. (Hanne), Hout, A.H. (Annemarie) van der, Wijnen, J.T. (Juul), Roozendaal, K.E. (Kees) van, Mensenkamp, A.R. (Arjen), Ouweland, A.M.W. (Ans) van den, Deurzen, C.H.M. (Carolien) van, Luijt, R.B. (Rob) van der, Olah, E., Díez, O. (Orland), Lázaro, C. (Conxi), Blanco, I. (Ignacio), Teulé, A. (A.), Menéndez, M. (Mireia), Jakubowska, A. (Anna), Lubinski, J. (Jan), Cybulski, C. (Cezary), Gronwald, J. (Jacek), Jaworska-Bieniek, K. (Katarzyna), Durda, K. (Katarzyna), Arason, A. (Adalgeir), Maugard, C., Soucy, P. (Penny), Montagna, M. (Marco), Agata, S. (Simona), Teixeira, P.J., Olswold, C. (Curtis), Lindor, N.M. (Noralane), Pankratz, V.S. (Shane), Hallberg, B. (Boubou), Wang, X. (Xianshu), Szabo, C. (Csilla), Vijai, J. (Joseph), Jacobs, L. (Lauren), Corines, M. (Marina), Lincoln, A. (Anne), Berger, A. (Andreas), Fink-Retter, A. (Anneliese), Singer, C.F. (Christian), Rappaport, C. (Christine), Kaulich, D.G. (Daphne Gschwantler), Pfeiler, G. (Georg), Tea, M.-K., Phelan, C. (Catherine), Mai, P.L. (Phuong), Greene, M.H. (Mark), Rennert, G. (Gad), Imyanitov, E.N. (Evgeny), Glendon, G. (Gord), Toland, A.E. (Amanda), Bojesen, A. (Anders), Pedersen, I.S. (Inge Sokilde), Jensen, U.B., Caligo, M.A. (Maria), Friedman, E. (Eitan), Berger, R. (Raanan), Laitman, Y. (Yael), Rantala, J. (Johanna), Arver, B. (Brita Wasteson), Loman, N. (Niklas), Borg, Å. (Åke), Ehrencrona, H. (Hans), Olopade, O.I. (Olofunmilayo), Simard, J. (Jacques), Easton, D.F. (Douglas), Chenevix-Trench, G. (Georgia), Offit, K. (Kenneth), Couch, F.J. (Fergus), Antoniou, A.C. (Antonis), Kuchenbaecker, K.B. (Karoline), Neuhausen, S.L. (Susan), Robson, M. (Mark), Barrowdale, D. (Daniel), McGuffog, L. (Lesley), Mulligan, A.M. (Anna Marie), Andrulis, I.L. (Irene), Spurdle, A.B. (Amanda), Schmidt, M.K. (Marjanka), Schmutzler, R.K. (Rita), Engel, C. (Christoph), Wapenschmidt, B. (Barbara), Nevanlinna, H. (Heli), Thomassen, M. (Mads), Southey, M.C. (Melissa), Radice, P. (Paolo), Ramus, S.J. (Susan), Domchek, S.M. (Susan), Nathanson, K.L. (Katherine), Lee, A. (Andrew), Healey, S. (Sue), Nussbaum, R. (Robert), Rebbeck, R. (Timothy), Arun, B.K. (Banu), James, M. (Margaret), Karlan, B.Y. (Beth), Lester, K.J. (Kathryn), Cass, I. (Ilana), Terry, M.B. (Mary Beth), Daly, M.J. (Mark), Goldgar, D. (David), Buys, S.S. (Saundra), Janavicius, R. (Ramunas), Tihomirova, L. (Laima), Tung, N. (Nadine), Dorfling, C.M. (Cecilia), Rensburg, E.J. (Elizabeth) van, Steele, L. (Linda), Overeem Hansen, T. (Thomas) van, Ejlertsen, B. (Bent), Gerdes, A-M. (Anne-Marie), Nielsen, F. (Finn), Dennis, J. (Joe), Cunningham, J.M. (Julie), Hart, S. (Stewart), Slager, S. (Susan), Osorio, A. (Ana), Benítez, J. (Javier), Duran, M. (Mercedes), Weitzel, J.N. (Jeffrey), Tafur, I. (Isaac), Hander, M. (Mary), Peterlongo, P. (Paolo), Manoukian, S. (Siranoush), Peissel, B. (Bernard), Roversi, G. (Gaia), Scuvera, G. (Giulietta), Bonnani, B. (Bernardo), Mariani, P. (Paolo), Volorio, S. (Sara), Dolcetti, R. (Riccardo), Varesco, L. (Liliana), Papi, L. (Laura), Tibiletti, M.G. (Maria Grazia), Giannini, G. (Giuseppe), Fostira, F. (Florentia), Konstantopoulou, I. (I.), Garber, J. (Judy), Hamann, U. (Ute), Donaldson, A. (Alan), Brewer, C. (Carole), Foo, C. (Claire), Evans, D.G. (Gareth), Frost, D. (Debra), Eccles, D. (Diana), Douglas, F. (Fiona), Brady, A. (A.), Cook, J. (Jackie), Tischkowitz, M. (Marc), Adlard, L., Barwell, J. (Julian), Ong, K., Walker, L.J. (Lisa), Izatt, L. (Louise), Side, L. (Lucy), Kennedy, M.J. (John), Rogers, M.T. (Mark), Porteous, M.E. (Mary), Morrison, P.J. (Patrick), Platte, R. (Radka), Eeles, R. (Ros), Davidson, R. (Rosemarie), Hodgson, S. (Shirley), Ellis, S.D. (Steve), Godwin, A.K. (Andrew), Rhiem, K. (Kerstin), Meindl, A. (Alfons), Ditsch, N. (Nina), Arnold, N. (Norbert), Plendl, H. (Hansjoerg), Niederacher, D. (Dieter), Sutter, C. (Christian), Steinemann, D. (Doris), Bogdanova-Markov, N. (Nadja), Kast, K. (Karin), Varon-Mateeva, R. (Raymonda), Wang-Gohrke, S. (Shan), Gehrig, P.A. (Paola A.), Markiefka, B. (Birgid), Buecher, B. (Bruno), Lefol, C. (Cédrick), Stoppa-Lyonnet, D. (Dominique), Rouleau, E. (Etienne), Prieur, F. (Fabienne), Damiola, F. (Francesca), Barjhoux, L. (Laure), Faivre, L. (Laurence), Longy, M. (Michel), Sevenet, N. (Nicolas), Sinilnikova, O. (Olga), Mazoyer, S. (Sylvie), Bonadona, V. (Valérie), Caux-Moncoutier, V. (Virginie), Isaacs, C. (Claudine), Van Maerken, T. (Tom), Claes, K.B.M. (Kathleen B.M.), Piedmonte, M. (Marion), Andrews, L. (Lesley), Hays, J. (John), Rodriguez, G.C. (Gustavo), Caldes, T. (Trinidad), Hoya, M. (Miguel) de La, Khan, S. (Sofia), Hogervorst, F.B.L. (Frans), Aalfs, C.M. (Cora), Lange, J.L. (J.) de, Meijers-Heijboer, E.J. (Hanne), Hout, A.H. (Annemarie) van der, Wijnen, J.T. (Juul), Roozendaal, K.E. (Kees) van, Mensenkamp, A.R. (Arjen), Ouweland, A.M.W. (Ans) van den, Deurzen, C.H.M. (Carolien) van, Luijt, R.B. (Rob) van der, Olah, E., Díez, O. (Orland), Lázaro, C. (Conxi), Blanco, I. (Ignacio), Teulé, A. (A.), Menéndez, M. (Mireia), Jakubowska, A. (Anna), Lubinski, J. (Jan), Cybulski, C. (Cezary), Gronwald, J. (Jacek), Jaworska-Bieniek, K. (Katarzyna), Durda, K. (Katarzyna), Arason, A. (Adalgeir), Maugard, C., Soucy, P. (Penny), Montagna, M. (Marco), Agata, S. (Simona), Teixeira, P.J., Olswold, C. (Curtis), Lindor, N.M. (Noralane), Pankratz, V.S. (Shane), Hallberg, B. (Boubou), Wang, X. (Xianshu), Szabo, C. (Csilla), Vijai, J. (Joseph), Jacobs, L. (Lauren), Corines, M. (Marina), Lincoln, A. (Anne), Berger, A. (Andreas), Fink-Retter, A. (Anneliese), Singer, C.F. (Christian), Rappaport, C. (Christine), Kaulich, D.G. (Daphne Gschwantler), Pfeiler, G. (Georg), Tea, M.-K., Phelan, C. (Catherine), Mai, P.L. (Phuong), Greene, M.H. (Mark), Rennert, G. (Gad), Imyanitov, E.N. (Evgeny), Glendon, G. (Gord), Toland, A.E. (Amanda), Bojesen, A. (Anders), Pedersen, I.S. (Inge Sokilde), Jensen, U.B., Caligo, M.A. (Maria), Friedman, E. (Eitan), Berger, R. (Raanan), Laitman, Y. (Yael), Rantala, J. (Johanna), Arver, B. (Brita Wasteson), Loman, N. (Niklas), Borg, Å. (Åke), Ehrencrona, H. (Hans), Olopade, O.I. (Olofunmilayo), Simard, J. (Jacques), Easton, D.F. (Douglas), Chenevix-Trench, G. (Georgia), Offit, K. (Kenneth), Couch, F.J. (Fergus), and Antoniou, A.C. (Antonis)
Abstract: Introduction: More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 mutation carriers and the general population for several loci, no study has comprehensively evaluated the associations of all known BC susceptibility alleles with risk of BC subtypes in BRCA1 and BRCA2 carriers. Methods: We used data from 15,252 BRCA1 and 8,211 BRCA2 carriers to analyze the associations between approximately 200,000 genetic variants on the iCOGS array and risk of BC subtypes defined by estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and triple-negative- (TN) status; morphologic subtypes; histological grade; and nodal involvement. Results: The estimated BC hazard ratios (HRs) for the 74 known BC alleles in BRCA1 carriers exhibited moderate correlations with the corresponding odds ratios from the general population. However, their associations with ER-positive BC in BRCA1 carriers were more consistent with the ER-positive ass
Published: 2014
Full Text: View/download PDF

19. Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

Author: Kuchenbaecker, KB, Neuhausen, SL, Robson, M, Barrowdale, D, McGuffog, L, Mulligan, AM, Andrulis, IL, Spurdle, AB, Schmidt, MK, Schmutzler, RK, Engel, C, Wappenschmidt, B, Nevanlinna, H, Thomassen, M, Southey, M, Radice, P, Ramus, SJ, Domchek, SM, Nathanson, KL, Lee, A, Healey, S, Nussbaum, RL, Rebbeck, TR, Arun, BK, James, P, Karlan, BY, Lester, J, Cass, I, Terry, MB, Daly, MB, Goldgar, DE, Buys, SS, Janavicius, R, Tihomirova, L, Tung, N, Dorfling, CM, van Rensburg, EJ, Steele, L, Hansen, TVO, Ejlertsen, B, Gerdes, A-M, Nielsen, FC, Dennis, J, Cunningham, J, Hart, S, Slager, S, Osorio, A, Benitez, J, Duran, M, Weitzel, JN, Tafur, I, Hander, M, Peterlongo, P, Manoukian, S, Peissel, B, Roversi, G, Scuvera, G, Bonanni, B, Mariani, P, Volorio, S, Dolcetti, R, Varesco, L, Papi, L, Tibiletti, MG, Giannini, G, Fostira, F, Konstantopoulou, I, Garber, J, Hamann, U, Donaldson, A, Brewer, C, Foo, C, Evans, DG, Frost, D, Eccles, D, Douglas, F, Brady, A, Cook, J, Tischkowitz, M, Adlard, J, Barwell, J, Ong, K-R, Walker, L, Izatt, L, Side, LE, Kennedy, MJ, Rogers, MT, Porteous, ME, Morrison, PJ, Platte, R, Eeles, R, Davidson, R, Hodgson, S, Ellis, S, Godwin, AK, Rhiem, K, Meindl, A, Ditsch, N, Arnold, N, Plendl, H, Niederacher, D, Sutter, C, Steinemann, D, Bogdanova-Markov, N, Kast, K, Varon-Mateeva, R, Wang-Gohrke, S, Gehrig, A, Markiefka, B, Buecher, B, Lefol, C, Stoppa-Lyonnet, D, Rouleau, E, Prieur, F, Damiola, F, Barjhoux, L, Faivre, L, Longy, M, Sevenet, N, Sinilnikova, OM, Mazoyer, S, Bonadona, V, Caux-Moncoutier, V, Isaacs, C, Van Maerken, T, Claes, K, Piedmonte, M, Andrews, L, Hays, J, Rodriguez, GC, Caldes, T, de la Hoya, M, Khan, S, Hogervorst, FBL, Aalfs, CM, de lange, JL, Meijers-Heijboer, HEJ, van der Hout, AH, Wijnen, JT, van Roozendaal, KEP, Mensenkamp, AR, van den Ouweland, AMW, van Deurzen, CHM, van der Luijt, RB, Olah, E, Diez, O, Lazaro, C, Blanco, I, Teule, A, Menendez, M, Jakubowska, A, Lubinski, J, Cybulski, C, Gronwald, J, Jaworska-Bieniek, K, Durda, K, Arason, A, Maugard, C, Soucy, P, Montagna, M, Agata, S, Teixeira, MR, Olswold, C, Lindor, N, Pankratz, VS, Hallberg, E, Wang, X, Szabo, CI, Vijai, J, Jacobs, L, Corines, M, Lincoln, A, Berger, A, Fink-Retter, A, Singer, CF, Rappaport, C, Kaulich, DG, Pfeiler, G, Tea, M-K, Phelan, CM, Mai, PL, Greene, MH, Rennert, G, Imyanitov, EN, Glendon, G, Toland, AE, Bojesen, A, Pedersen, IS, Jensen, UB, Caligo, MA, Friedman, E, Berger, R, Laitman, Y, Rantala, J, Arver, B, Loman, N, Borg, A, Ehrencrona, H, Olopade, OI, Simard, J, Easton, DF, Chenevix-Trench, G, Offit, K, Couch, FJ, Antoniou, AC, Kuchenbaecker, KB, Neuhausen, SL, Robson, M, Barrowdale, D, McGuffog, L, Mulligan, AM, Andrulis, IL, Spurdle, AB, Schmidt, MK, Schmutzler, RK, Engel, C, Wappenschmidt, B, Nevanlinna, H, Thomassen, M, Southey, M, Radice, P, Ramus, SJ, Domchek, SM, Nathanson, KL, Lee, A, Healey, S, Nussbaum, RL, Rebbeck, TR, Arun, BK, James, P, Karlan, BY, Lester, J, Cass, I, Terry, MB, Daly, MB, Goldgar, DE, Buys, SS, Janavicius, R, Tihomirova, L, Tung, N, Dorfling, CM, van Rensburg, EJ, Steele, L, Hansen, TVO, Ejlertsen, B, Gerdes, A-M, Nielsen, FC, Dennis, J, Cunningham, J, Hart, S, Slager, S, Osorio, A, Benitez, J, Duran, M, Weitzel, JN, Tafur, I, Hander, M, Peterlongo, P, Manoukian, S, Peissel, B, Roversi, G, Scuvera, G, Bonanni, B, Mariani, P, Volorio, S, Dolcetti, R, Varesco, L, Papi, L, Tibiletti, MG, Giannini, G, Fostira, F, Konstantopoulou, I, Garber, J, Hamann, U, Donaldson, A, Brewer, C, Foo, C, Evans, DG, Frost, D, Eccles, D, Douglas, F, Brady, A, Cook, J, Tischkowitz, M, Adlard, J, Barwell, J, Ong, K-R, Walker, L, Izatt, L, Side, LE, Kennedy, MJ, Rogers, MT, Porteous, ME, Morrison, PJ, Platte, R, Eeles, R, Davidson, R, Hodgson, S, Ellis, S, Godwin, AK, Rhiem, K, Meindl, A, Ditsch, N, Arnold, N, Plendl, H, Niederacher, D, Sutter, C, Steinemann, D, Bogdanova-Markov, N, Kast, K, Varon-Mateeva, R, Wang-Gohrke, S, Gehrig, A, Markiefka, B, Buecher, B, Lefol, C, Stoppa-Lyonnet, D, Rouleau, E, Prieur, F, Damiola, F, Barjhoux, L, Faivre, L, Longy, M, Sevenet, N, Sinilnikova, OM, Mazoyer, S, Bonadona, V, Caux-Moncoutier, V, Isaacs, C, Van Maerken, T, Claes, K, Piedmonte, M, Andrews, L, Hays, J, Rodriguez, GC, Caldes, T, de la Hoya, M, Khan, S, Hogervorst, FBL, Aalfs, CM, de lange, JL, Meijers-Heijboer, HEJ, van der Hout, AH, Wijnen, JT, van Roozendaal, KEP, Mensenkamp, AR, van den Ouweland, AMW, van Deurzen, CHM, van der Luijt, RB, Olah, E, Diez, O, Lazaro, C, Blanco, I, Teule, A, Menendez, M, Jakubowska, A, Lubinski, J, Cybulski, C, Gronwald, J, Jaworska-Bieniek, K, Durda, K, Arason, A, Maugard, C, Soucy, P, Montagna, M, Agata, S, Teixeira, MR, Olswold, C, Lindor, N, Pankratz, VS, Hallberg, E, Wang, X, Szabo, CI, Vijai, J, Jacobs, L, Corines, M, Lincoln, A, Berger, A, Fink-Retter, A, Singer, CF, Rappaport, C, Kaulich, DG, Pfeiler, G, Tea, M-K, Phelan, CM, Mai, PL, Greene, MH, Rennert, G, Imyanitov, EN, Glendon, G, Toland, AE, Bojesen, A, Pedersen, IS, Jensen, UB, Caligo, MA, Friedman, E, Berger, R, Laitman, Y, Rantala, J, Arver, B, Loman, N, Borg, A, Ehrencrona, H, Olopade, OI, Simard, J, Easton, DF, Chenevix-Trench, G, Offit, K, Couch, FJ, and Antoniou, AC
Abstract: INTRODUCTION: More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 mutation carriers and the general population for several loci, no study has comprehensively evaluated the associations of all known BC susceptibility alleles with risk of BC subtypes in BRCA1 and BRCA2 carriers. METHODS: We used data from 15,252 BRCA1 and 8,211 BRCA2 carriers to analyze the associations between approximately 200,000 genetic variants on the iCOGS array and risk of BC subtypes defined by estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and triple-negative- (TN) status; morphologic subtypes; histological grade; and nodal involvement. RESULTS: The estimated BC hazard ratios (HRs) for the 74 known BC alleles in BRCA1 carriers exhibited moderate correlations with the corresponding odds ratios from the general population. However, their associations with ER-positive BC in BRCA1 carriers were more consistent with the ER-positive associations in the general population (intraclass correlation (ICC) = 0.61, 95% confidence interval (CI): 0.45 to 0.74), and the same was true when considering ER-negative associations in both groups (ICC = 0.59, 95% CI: 0.42 to 0.72). Similarly, there was strong correlation between the ER-positive associations for BRCA1 and BRCA2 carriers (ICC = 0.67, 95% CI: 0.52 to 0.78), whereas ER-positive associations in any one of the groups were generally inconsistent with ER-negative associations in any of the others. After stratifying by ER status in mutation carriers, additional significant associations were observed. Several previously unreported variants exhibited associations at P <10(-6) in the analyses by PR status, HER2 status, TN phenotype, morphologic subtypes, histological grade and nodal involvement
Published: 2014

20. Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

Author: Kuchenbaecker, K, Neuhausen, S, Robson, M, Barrowdale, D, Mcguffog, L, Mulligan, A, Andrulis, I, Spurdle, A, Schmidt, M, Schmutzler, R, Engel, C, Wappenschmidt, B, Nevanlinna, H, Thomassen, M, Southey, M, Radice, P, Ramus, S, Domchek, S, Nathanson, K, Lee, A, Healey, S, Nussbaum, R, Rebbeck, T, Arun, B, James, P, Karlan, B, Lester, J, Cass, I, Breast Cancer Family, R, Terry, M, Daly, M, Goldgar, D, Buys, S, Janavicius, R, Tihomirova, L, Tung, N, Dorfling, C, van Rensburg, E, Steele, L, v. O. Hansen, T, Ejlertsen, B, Gerdes, A, Nielsen, F, Dennis, J, Cunningham, J, Hart, S, Slager, S, Osorio, A, Benitez, J, Duran, M, Weitzel, J, Tafur, I, Hander, M, Peterlongo, P, Manoukian, S, Peissel, B, Roversi, G, Scuvera, G, Bonanni, B, Mariani, P, Volorio, S, Dolcetti, R, Varesco, L, Papi, L, Tibiletti, M, Giannini, G, Fostira, F, Konstantopoulou, I, Garber, J, Hamann, U, Donaldson, A, Brewer, C, Foo, C, Evans, D, Frost, D, Eccles, D, Embrace, S, Douglas, F, Brady, A, Cook, J, Tischkowitz, M, Adlard, J, Barwell, J, Ong, K, Walker, L, Izatt, L, Side, L, Kennedy, M, Rogers, M, Porteous, M, Morrison, P, Platte, R, Eeles, R, Davidson, R, Hodgson, S, Ellis, S, Godwin, A, Rhiem, K, Meindl, A, Ditsch, N, Arnold, N, Plendl, H, Niederacher, D, Sutter, C, Steinemann, D, Bogdanova Markov, N, Kast, K, Varon Mateeva, R, Wang Gohrke, S, Gehrig, A, Markiefka, B, Buecher, B, Lefol, C, Stoppa Lyonnet, D, Rouleau, E, Prieur, F, Damiola, F, GEMO Study, C, Barjhoux, L, Faivre, L, Longy, M, Sevenet, N, Sinilnikova, O, Mazoyer, S, Bonadona, V, Caux Moncoutier, V, Isaacs, C, Van Maerken, T, Claes, K, Piedmonte, M, Andrews, L, Hays, J, Rodriguez, G, Caldes, T, de la Hoya, M, Khan, S, Hogervorst, F, Aalfs, C, de Lange, J, Meijers Heijboer, H, van der Hout, A, Wijnen, J, van Roozendaal, K, Mensenkamp, A, van den Ouweland, A, van Deurzen, C, van der Luijt, R, Hebon, Olah, E, Diez, O, Lazaro, C, Blanco, I, Teulé, A, Menendez, M, Jakubowska, A, Lubinski, J, Cybulski, C, Gronwald, J, Jaworska Bieniek, K, Durda, K, Arason, A, Maugard, C, Soucy, P, Montagna, M, Agata, S, Teixeira, M, Kconfab, I, Olswold, C, Lindor, N, Pankratz, V, Hallberg, E, Wang, X, Szabo, C, Vijai, J, Jacobs, L, Corines, M, Lincoln, A, Berger, A, Fink Retter, A, Singer, C, Rappaport, C, Kaulich, D, Pfeiler, G, Tea, M, Phelan, C, Mai, P, Greene, M, Rennert, G, Imyanitov, E, Glendon, G, Toland, A, Bojesen, A, Pedersen, I, Jensen, U, Caligo, M, Friedman, E, Berger, R, Laitman, Y, Rantala, J, Arver, B, Loman, N, Borg, A, Ehrencrona, H, Olopade, O, Simard, J, Easton, D, Chenevix Trench, G, Offit, K, Couch, F, Antoniou, A, Cimba, Kuchenbaecker, KB, Neuhausen, SL, McGuffog, L, Mulligan, AM, Andrulis, IL, Spurdle, AB, Schmidt, MK, Schmutzler, RK, Ramus, SJ, Domchek, SM, Nathanson, KL, Nussbaum, RL, Rebbeck, TR, Arun, BK, Karlan, BY, Breast Cancer Family Registry, Terry, MB, Daly, MB, Goldgar, DE, Buys, SS, Dorfling, CM, van Rensburg, EJ, Gerdes, AM, Nielsen, FC, Weitzel, JN, ROVERSI, GAIA, Tibiletti, MG, Evans, DG, EMBRACE Study, Ong, KR, Side, LE, Kennedy, MJ, Rogers, MT, Porteous, ME, Morrison, PJ, Godwin, AK, GEMO Study Collaborators, Sinilnikova, OM, Rodriguez, GC, Hogervorst, FB, Aalfs, CM, de Lange, JL, Meijers Heijboer, HE, van der Hout, AH, Wijnen, JT, van Roozendaal, KE, Mensenkamp, AR, van den Ouweland, AM, van Deurzen, CH, van der Luijt, RB, HEBON, Teixeira, MR, KConFab, Investigators, Pankratz, VS, Szabo, CI, Singer, CF, Kaulich, DG, Tea, MK, Phelan, CM, Mai, PL, Greene, MH, Imyanitov, EN, Toland, AE, Pedersen, IS, Jensen, UB, Caligo, MA, Olopade, OI, Easton, DF, Couch, FJ, Antoniou, AC, CIMBA, Kuchenbaecker, K, Neuhausen, S, Robson, M, Barrowdale, D, Mcguffog, L, Mulligan, A, Andrulis, I, Spurdle, A, Schmidt, M, Schmutzler, R, Engel, C, Wappenschmidt, B, Nevanlinna, H, Thomassen, M, Southey, M, Radice, P, Ramus, S, Domchek, S, Nathanson, K, Lee, A, Healey, S, Nussbaum, R, Rebbeck, T, Arun, B, James, P, Karlan, B, Lester, J, Cass, I, Breast Cancer Family, R, Terry, M, Daly, M, Goldgar, D, Buys, S, Janavicius, R, Tihomirova, L, Tung, N, Dorfling, C, van Rensburg, E, Steele, L, v. O. Hansen, T, Ejlertsen, B, Gerdes, A, Nielsen, F, Dennis, J, Cunningham, J, Hart, S, Slager, S, Osorio, A, Benitez, J, Duran, M, Weitzel, J, Tafur, I, Hander, M, Peterlongo, P, Manoukian, S, Peissel, B, Roversi, G, Scuvera, G, Bonanni, B, Mariani, P, Volorio, S, Dolcetti, R, Varesco, L, Papi, L, Tibiletti, M, Giannini, G, Fostira, F, Konstantopoulou, I, Garber, J, Hamann, U, Donaldson, A, Brewer, C, Foo, C, Evans, D, Frost, D, Eccles, D, Embrace, S, Douglas, F, Brady, A, Cook, J, Tischkowitz, M, Adlard, J, Barwell, J, Ong, K, Walker, L, Izatt, L, Side, L, Kennedy, M, Rogers, M, Porteous, M, Morrison, P, Platte, R, Eeles, R, Davidson, R, Hodgson, S, Ellis, S, Godwin, A, Rhiem, K, Meindl, A, Ditsch, N, Arnold, N, Plendl, H, Niederacher, D, Sutter, C, Steinemann, D, Bogdanova Markov, N, Kast, K, Varon Mateeva, R, Wang Gohrke, S, Gehrig, A, Markiefka, B, Buecher, B, Lefol, C, Stoppa Lyonnet, D, Rouleau, E, Prieur, F, Damiola, F, GEMO Study, C, Barjhoux, L, Faivre, L, Longy, M, Sevenet, N, Sinilnikova, O, Mazoyer, S, Bonadona, V, Caux Moncoutier, V, Isaacs, C, Van Maerken, T, Claes, K, Piedmonte, M, Andrews, L, Hays, J, Rodriguez, G, Caldes, T, de la Hoya, M, Khan, S, Hogervorst, F, Aalfs, C, de Lange, J, Meijers Heijboer, H, van der Hout, A, Wijnen, J, van Roozendaal, K, Mensenkamp, A, van den Ouweland, A, van Deurzen, C, van der Luijt, R, Hebon, Olah, E, Diez, O, Lazaro, C, Blanco, I, Teulé, A, Menendez, M, Jakubowska, A, Lubinski, J, Cybulski, C, Gronwald, J, Jaworska Bieniek, K, Durda, K, Arason, A, Maugard, C, Soucy, P, Montagna, M, Agata, S, Teixeira, M, Kconfab, I, Olswold, C, Lindor, N, Pankratz, V, Hallberg, E, Wang, X, Szabo, C, Vijai, J, Jacobs, L, Corines, M, Lincoln, A, Berger, A, Fink Retter, A, Singer, C, Rappaport, C, Kaulich, D, Pfeiler, G, Tea, M, Phelan, C, Mai, P, Greene, M, Rennert, G, Imyanitov, E, Glendon, G, Toland, A, Bojesen, A, Pedersen, I, Jensen, U, Caligo, M, Friedman, E, Berger, R, Laitman, Y, Rantala, J, Arver, B, Loman, N, Borg, A, Ehrencrona, H, Olopade, O, Simard, J, Easton, D, Chenevix Trench, G, Offit, K, Couch, F, Antoniou, A, Cimba, Kuchenbaecker, KB, Neuhausen, SL, McGuffog, L, Mulligan, AM, Andrulis, IL, Spurdle, AB, Schmidt, MK, Schmutzler, RK, Ramus, SJ, Domchek, SM, Nathanson, KL, Nussbaum, RL, Rebbeck, TR, Arun, BK, Karlan, BY, Breast Cancer Family Registry, Terry, MB, Daly, MB, Goldgar, DE, Buys, SS, Dorfling, CM, van Rensburg, EJ, Gerdes, AM, Nielsen, FC, Weitzel, JN, ROVERSI, GAIA, Tibiletti, MG, Evans, DG, EMBRACE Study, Ong, KR, Side, LE, Kennedy, MJ, Rogers, MT, Porteous, ME, Morrison, PJ, Godwin, AK, GEMO Study Collaborators, Sinilnikova, OM, Rodriguez, GC, Hogervorst, FB, Aalfs, CM, de Lange, JL, Meijers Heijboer, HE, van der Hout, AH, Wijnen, JT, van Roozendaal, KE, Mensenkamp, AR, van den Ouweland, AM, van Deurzen, CH, van der Luijt, RB, HEBON, Teixeira, MR, KConFab, Investigators, Pankratz, VS, Szabo, CI, Singer, CF, Kaulich, DG, Tea, MK, Phelan, CM, Mai, PL, Greene, MH, Imyanitov, EN, Toland, AE, Pedersen, IS, Jensen, UB, Caligo, MA, Olopade, OI, Easton, DF, Couch, FJ, Antoniou, AC, and CIMBA
Abstract: Introduction: More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 mutation carriers and the general population for several loci, no study has comprehensively evaluated the associations of all known BC susceptibility alleles with risk of BC subtypes in BRCA1 and BRCA2 carriers. Methods: We used data from 15,252 BRCA1 and 8,211 BRCA2 carriers to analyze the associations between approximately 200,000 genetic variants on the iCOGS array and risk of BC subtypes defined by estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and triple-negative- (TN) status; morphologic subtypes; histological grade; and nodal involvement. Results: The estimated BC hazard ratios (HRs) for the 74 known BC alleles in BRCA1 carriers exhibited moderate correlations with the corresponding odds ratios from the general population. However, their associations with ER-positive BC in BRCA1 carriers were more consistent with the ER-positive associations in the general population (intraclass correlation (ICC)=0.61, 95% confidence interval (CI): 0.45 to 0.74), and the same was true when considering ER-negative associations in both groups (ICC=0.59, 95% CI: 0.42 to 0.72). Similarly, there was strong correlation between the ER-positive associations for BRCA1 and BRCA2 carriers (ICC=0.67, 95% CI: 0.52 to 0.78), whereas ER-positive associations in any one of the groups were generally inconsistent with ER-negative associations in any of the others. After stratifying by ER status in mutation carriers, additional significant associations were observed. Several previously unreported variants exhibited associations at P <10-6 in the analyses by PR status, HER2 status, TN phenotype, morphologic subtypes, histological grade and nodal involvement. Con
Published: 2014

21. 115 A Diagnostic Genetic Test for the Physical Mapping of Germline Rearrangements in the Susceptibility Breast Cancer Genes BRCA1 and BRCA2

Author: Ceppi, M., primary, Cheeseman, K., additional, Rouleau, E., additional, Thomas, A., additional, Briaux, A., additional, Lefol, C., additional, Walrafen, P., additional, Bensimon, A., additional, Conseiller, E., additional, and Lidereau, R., additional
Published: 2012
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22. P2-13-10: Detection, Visualization and High Resolution Physical Mapping of Large Rearrangements by Molecular Combing in the Hereditary Breast Cancer Genes BRCA1 and BRCA2.

Author: Ceppi, M, primary, Roleau, E, additional, Cheeseman, K, additional, Thomas, A, additional, Briaux, A, additional, Lefol, C, additional, Walrafen, P, additional, Bensimon, A, additional, Lidereau, R, additional, and Conseiller, E, additional
Published: 2011
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23. Premiers travaux sur l'existence et la nature de sites d'attachement MLO/insecte vecteur

Author: Lefol, C., Lherminier, Jeannine, Boudon-Padieu, E., Meignoz, R., Caudwell, A., ProdInra, Migration, Laboratoire de recherches sur les Phytoplasmes, and Institut National de la Recherche Agronomique (INRA)
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], TEST ELISA
Published: 1993

24. Attachment of flavescence doree pathogen (mlo) to leafhopper vectors and other insects

Author: Lefol, C., Caudwell, A., Lherminier, Jeannine, Larrue, J., ProdInra, Migration, Laboratoire de recherches sur les Phytoplasmes, and Institut National de la Recherche Agronomique (INRA)
Subjects: [SDV] Life Sciences [q-bio], MLO, [SDV]Life Sciences [q-bio]
Published: 1993

25. Breast and ovarian cancer predisposition due to de novo BRCA1and BRCA2mutations

Author: Golmard, L, Delnatte, C, Laugé, A, Moncoutier, V, Lefol, C, Abidallah, K, Tenreiro, H, Copigny, F, Giraudeau, M, Guy, C, Barbaroux, C, Amorim, G, Briaux, A, Guibert, V, Tarabeux, J, Caputo, S, Collet, A, Gesta, P, Ingster, O, Stern, M-H, Rouleau, E, de Pauw, A, Gauthier-Villars, M, Buecher, B, Bézieau, S, Stoppa-Lyonnet, D, and Houdayer, C
Abstract: BRCA1and BRCA2are the two major genes predisposing to breast and ovarian cancer. Whereas high de novomutation rates have been demonstrated for several genes, only 11 cases of de novo BRCA1/2mutations have been reported to date and the BRCA1/2 de novomutation rate remains unknown. The present study was designed to fill this gap based on a series of 12 805 consecutive unrelated patients diagnosed with breast and/or ovarian cancer who met the inclusion criteria for BRCA1/2gene analysis according to French guidelines. BRCA1/2mutations were detected in 1527 (12%) patients, and three BRCA1mutations and one BRCA2mutation were de novo. The BRCA1/2 de novomutation rate was estimated to be 0.3% (0.1%; 0.7%). Although rare, it may be useful to take the possibility of de novo BRCA1/2mutation into account in genetic counseling of relatives and to improve the understanding of complex family histories of breast and ovarian cancers.
Published: 2016
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26. Immunofluorescent staining of sclerotinia ascospores on canola petals

Author: Lefol, C., primary and Morrall, R.A.A., additional
Published: 1996
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27. Propagation of Flavescence dorée MLO (Mycoplasma-like Organism) in the Leafhopper Vector Euscelidius variegatus Kbm

Author: Lefol, C, primary, Lherminier, J, additional, Boudon-Padieu, E, additional, Larrue, J, additional, Louis, C, additional, and Caudwell, A, additional
Published: 1994
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28. Attachment of the Flavescence doree pathogen (MLO) to leafhopper vectors and other insects

Author: LEFOL, C., primary, CAUDWELL, A., additional, LHERMINIER, J., additional, and LARRUE, J., additional
Published: 1993
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29. An entire exon 3 germ-line rearrangement in the BRCA2 gene: pathogenic relevance of exon 3 deletion in breast cancer predisposition

Author: Demange Liliane, Limacher Jean, Noguès Catherine, Caron Olivier, Bièche Ivan, Lefol Cédrick, Caputo Sandrine, Schultz Inès, Rouleau Etienne, Muller Danièle, Lidereau Rosette, Fricker Jean, and Abecassis Joseph
Subjects: Internal medicine, RC31-1245, Genetics, QH426-470
Abstract: Abstract Background Germ-line mutations in the BRCA1 and BRCA2 genes are major contributors to hereditary breast/ovarian cancer. Large rearrangements are less frequent in the BRCA2 gene than in BRCA1. We report, here, the first total deletion of exon 3 in the BRCA2 gene that was detected during screening of 2058 index cases from breast/ovarian cancer families for BRCA2 large rearrangements. Deletion of exon 3, which is in phase, does not alter the reading frame. Low levels of alternative transcripts lacking exon 3 (Δ3 delta3 transcript) have been reported in normal tissues, which raises the question whether deletion of exon 3 is pathogenic. Methods Large BRCA2 rearrangements were analysed by QMPSF (Quantitative Multiplex PCR of Short Fluorescent Fragments) or MLPA (Multiplex Ligation-Dependent Probe Amplification). The exon 3 deletion was characterized with a "zoom-in" dedicated CGH array to the BRCA2 gene and sequencing. To determine the effect of exon 3 deletion and assess its pathogenic effect, three methods of transcript quantification were used: fragment analysis of FAM-labelled PCR products, specific allelic expression using an intron 2 polymorphism and competitive quantitative RT-PCR. Results Large rearrangements of BRCA2 were detected in six index cases out of 2058 tested (3% of all deleterious BRCA2 mutations). This study reports the first large rearrangement of the BRCA2 gene that includes all of exon 3 and leads to an in frame deletion of exon 3 at the transcriptional level. Thirty five variants in exon 3 and junction regions of BRCA2 are also reported, that contribute to the interpretation of the pathogenicity of the deletion. The quantitative approaches showed that there are three classes of delta3 BRCA2 transcripts (low, moderate and exclusive). Exclusive expression of the delta3 transcript by the mutant allele and segregation data provide evidence for a causal effect of the exon 3 deletion. Conclusion This paper highlights that large rearrangements and total deletion of exon 3 in the BRCA2 gene could contribute to hereditary breast and/or ovarian cancer. In addition, our findings suggest that, to interpret the pathogenic effect of any variants of exon 3, both accurate transcript quantification and co-segregation analysis are required.
Published: 2011
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30. Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

Author: Kuchenbaecker, Karoline B, Neuhausen, Susan L, Robson, Mark, Barrowdale, Daniel, McGuffog, Lesley, Mulligan, Anna Marie, Andrulis, Irene L, Spurdle, Amanda B, Schmidt, Marjanka K, Schmutzler, Rita K, Engel, Christoph, Wappenschmidt, Barbara, Nevanlinna, Heli, Thomassen, Mads, Southey, Melissa, Radice, Paolo, Ramus, Susan J, Domchek, Susan M, Nathanson, Katherine L, Lee, Andrew, Healey, Sue, Nussbaum, Robert L, Rebbeck, Timothy R, Arun, Banu K, James, Paul, Karlan, Beth Y, Lester, Jenny, Cass, Ilana, Breast Cancer Family Registry, the, Terry, Mary Beth, Daly, Mary B, Goldgar, David E, Buys, Saundra S, Janavicius, Ramunas, Tihomirova, Laima, Tung, Nadine, Dorfling, Cecilia M, van Rensburg, Elizabeth J, Steele, Linda, v O Hansen, Thomas, Ejlertsen, Bent, Gerdes, Anne-Marie, Nielsen, Finn C, Dennis, Joe, Cunningham, Julie, Hart, Steven, Slager, Susan, Osorio, Ana, Benitez, Javier, Duran, Mercedes, Weitzel, Jeffrey N, Tafur, Isaac, Hander, Mary, Peterlongo, Paolo, Manoukian, Siranoush, Peissel, Bernard, Roversi, Gaia, Scuvera, Giulietta, Bonanni, Bernardo, Mariani, Paolo, Volorio, Sara, Dolcetti, Riccardo, Varesco, Liliana, Papi, Laura, Tibiletti, Maria Grazia, Giannini, Giuseppe, Fostira, Florentia, Konstantopoulou, Irene, Garber, Judy, Hamann, Ute, Donaldson, Alan, Brewer, Carole, Foo, Claire, Evans, D Gareth, Frost, Debra, Eccles, Diana, EMBRACE Study, the, Douglas, Fiona, Brady, Angela, Cook, Jackie, Tischkowitz, Marc, Adlard, Julian, Barwell, Julian, Ong, Kai-ren, Walker, Lisa, Izatt, Louise, Side, Lucy E, Kennedy, M John, Rogers, Mark T, Porteous, Mary E, Morrison, Patrick J, Platte, Radka, Eeles, Ros, Davidson, Rosemarie, Hodgson, Shirley, Ellis, Steve, Godwin, Andrew K, Rhiem, Kerstin, Meindl, Alfons, Ditsch, Nina, Arnold, Norbert, Plendl, Hansjoerg, Niederacher, Dieter, Sutter, Christian, Steinemann, Doris, Bogdanova-Markov, Nadja, Kast, Karin, Varon-Mateeva, Raymonda, Wang-Gohrke, Shan, Gehrig, Andrea, Markiefka, Birgid, Buecher, Bruno, Lefol, Cédrick, Stoppa-Lyonnet, Dominique, Rouleau, Etienne, Prieur, Fabienne, Damiola, Francesca, GEMO Study Collaborators, the, Barjhoux, Laure, Faivre, Laurence, Longy, Michel, Sevenet, Nicolas, Sinilnikova, Olga M, Mazoyer, Sylvie, Bonadona, Valérie, Caux-Moncoutier, Virginie, Isaacs, Claudine, Van Maerken, Tom, Claes, Kathleen, Piedmonte, Marion, Andrews, Lesley, Hays, John, Rodriguez, Gustavo C, Caldes, Trinidad, de la Hoya, Miguel, Khan, Sofia, Hogervorst, Frans BL, Aalfs, Cora M, de Lange, JL, Meijers-Heijboer, Hanne EJ, van der Hout, Annemarie H, Wijnen, Juul T, van Roozendaal, KEP, Mensenkamp, Arjen R, van den Ouweland, Ans MW, van Deurzen, Carolien HM, van der Luijt, Rob B, HEBON, ., Olah, Edith, Diez, Orland, Lazaro, Conxi, Blanco, Ignacio, Teulé, Alex, Menendez, Mireia, Jakubowska, Anna, Lubinski, Jan, Cybulski, Cezary, Gronwald, Jacek, Jaworska-Bieniek, Katarzyna, Durda, Katarzyna, Arason, Adalgeir, Maugard, Christine, Soucy, Penny, Montagna, Marco, Agata, Simona, Teixeira, Manuel R, KConFab Investigators, the, Olswold, Curtis, Lindor, Noralane, Pankratz, Vernon S, Hallberg, Emily, Wang, Xianshu, Szabo, Csilla I, Vijai, Joseph, Jacobs, Lauren, Corines, Marina, Lincoln, Anne, Berger, Andreas, Fink-Retter, Anneliese, Singer, Christian F, Rappaport, Christine, Gschwantler Kaulich, Daphne, Pfeiler, Georg, Tea, Muy-Kheng, Phelan, Catherine M, Mai, Phuong L, Greene, Mark H, Rennert, Gad, Imyanitov, Evgeny N, Glendon, Gord, Toland, Amanda Ewart, Bojesen, Anders, Pedersen, Inge Sokilde, Jensen, Uffe Birk, Caligo, Maria A, Friedman, Eitan, Berger, Raanan, Laitman, Yael, Rantala, Johanna, Arver, Brita, Loman, Niklas, Borg, Ake, Ehrencrona, Hans, Olopade, Olufunmilayo I, Simard, Jacques, Easton, Douglas F, Chenevix-Trench, Georgia, Offit, Kenneth, Couch, Fergus J, Antoniou, Antonis C, CIMBA, on behalf of, Kuchenbaecker, K, Neuhausen, S, Robson, M, Barrowdale, D, Mcguffog, L, Mulligan, A, Andrulis, I, Spurdle, A, Schmidt, M, Schmutzler, R, Engel, C, Wappenschmidt, B, Nevanlinna, H, Thomassen, M, Southey, M, Radice, P, Ramus, S, Domchek, S, Nathanson, K, Lee, A, Healey, S, Nussbaum, R, Rebbeck, T, Arun, B, James, P, Karlan, B, Lester, J, Cass, I, Breast Cancer Family, R, Terry, M, Daly, M, Goldgar, D, Buys, S, Janavicius, R, Tihomirova, L, Tung, N, Dorfling, C, van Rensburg, E, Steele, L, v. O. Hansen, T, Ejlertsen, B, Gerdes, A, Nielsen, F, Dennis, J, Cunningham, J, Hart, S, Slager, S, Osorio, A, Benitez, J, Duran, M, Weitzel, J, Tafur, I, Hander, M, Peterlongo, P, Manoukian, S, Peissel, B, Roversi, G, Scuvera, G, Bonanni, B, Mariani, P, Volorio, S, Dolcetti, R, Varesco, L, Papi, L, Tibiletti, M, Giannini, G, Fostira, F, Konstantopoulou, I, Garber, J, Hamann, U, Donaldson, A, Brewer, C, Foo, C, Evans, D, Frost, D, Eccles, D, Embrace, S, Douglas, F, Brady, A, Cook, J, Tischkowitz, M, Adlard, J, Barwell, J, Ong, K, Walker, L, Izatt, L, Side, L, Kennedy, M, Rogers, M, Porteous, M, Morrison, P, Platte, R, Eeles, R, Davidson, R, Hodgson, S, Ellis, S, Godwin, A, Rhiem, K, Meindl, A, Ditsch, N, Arnold, N, Plendl, H, Niederacher, D, Sutter, C, Steinemann, D, Bogdanova Markov, N, Kast, K, Varon Mateeva, R, Wang Gohrke, S, Gehrig, A, Markiefka, B, Buecher, B, Lefol, C, Stoppa Lyonnet, D, Rouleau, E, Prieur, F, Damiola, F, GEMO Study, C, Barjhoux, L, Faivre, L, Longy, M, Sevenet, N, Sinilnikova, O, Mazoyer, S, Bonadona, V, Caux Moncoutier, V, Isaacs, C, Van Maerken, T, Claes, K, Piedmonte, M, Andrews, L, Hays, J, Rodriguez, G, Caldes, T, de la Hoya, M, Khan, S, Hogervorst, F, Aalfs, C, de Lange, J, Meijers Heijboer, H, van der Hout, A, Wijnen, J, van Roozendaal, K, Mensenkamp, A, van den Ouweland, A, van Deurzen, C, van der Luijt, R, Hebon, Olah, E, Diez, O, Lazaro, C, Blanco, I, Teulé, A, Menendez, M, Jakubowska, A, Lubinski, J, Cybulski, C, Gronwald, J, Jaworska Bieniek, K, Durda, K, Arason, A, Maugard, C, Soucy, P, Montagna, M, Agata, S, Teixeira, M, Kconfab, I, Olswold, C, Lindor, N, Pankratz, V, Hallberg, E, Wang, X, Szabo, C, Vijai, J, Jacobs, L, Corines, M, Lincoln, A, Berger, A, Fink Retter, A, Singer, C, Rappaport, C, Kaulich, D, Pfeiler, G, Tea, M, Phelan, C, Mai, P, Greene, M, Rennert, G, Imyanitov, E, Glendon, G, Toland, A, Bojesen, A, Pedersen, I, Jensen, U, Caligo, M, Friedman, E, Berger, R, Laitman, Y, Rantala, J, Arver, B, Loman, N, Borg, A, Ehrencrona, H, Olopade, O, Simard, J, Easton, D, Chenevix Trench, G, Offit, K, Couch, F, Antoniou, A, Cimba, Lee, Andrew [0000-0003-0677-0252], Dennis, Joe [0000-0003-4591-1214], Tischkowitz, Marc [0000-0002-7880-0628], Easton, Douglas [0000-0003-2444-3247], Antoniou, Antonis [0000-0001-9223-3116], and Apollo - University of Cambridge Repository
Subjects: Cancer Research, Receptor, ErbB-2, Genes, BRCA2, BRCA, LOCI, Genes, BRCA1, MODIFIERS, VARIANTS, ErbB-2, 610 Medical sciences Medicine, Ductal, Receptors, Medicine and Health Sciences, INVESTIGATORS, Breast, skin and connective tissue diseases, Progesterone, Medicine(all), Carcinoma, Ductal, Breast, Middle Aged, Adult, Aged, Alleles, Breast Neoplasms, Carcinoma, Carcinoma, Lobular, Female, Genetic Predisposition to Disease, Heterozygote, Humans, Neoplasm Grading, Neoplasm Staging, Receptors, Estrogen, Receptors, Progesterone, Oncology, TUMOR SUBTYPES, Receptor, Research Article, MEDULLARY CARCINOMA, OVARIAN-CANCER, Lobular, GENOME-WIDE ASSOCIATION, CONSORTIUM, BRCA1, Estrogen, BRCA2, ESTROGEN-RECEPTOR, Genes
Abstract: Introduction More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 mutation carriers and the general population for several loci, no study has comprehensively evaluated the associations of all known BC susceptibility alleles with risk of BC subtypes in BRCA1 and BRCA2 carriers. Methods We used data from 15,252 BRCA1 and 8,211 BRCA2 carriers to analyze the associations between approximately 200,000 genetic variants on the iCOGS array and risk of BC subtypes defined by estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and triple-negative- (TN) status; morphologic subtypes; histological grade; and nodal involvement. Results The estimated BC hazard ratios (HRs) for the 74 known BC alleles in BRCA1 carriers exhibited moderate correlations with the corresponding odds ratios from the general population. However, their associations with ER-positive BC in BRCA1 carriers were more consistent with the ER-positive associations in the general population (intraclass correlation (ICC) = 0.61, 95% confidence interval (CI): 0.45 to 0.74), and the same was true when considering ER-negative associations in both groups (ICC = 0.59, 95% CI: 0.42 to 0.72). Similarly, there was strong correlation between the ER-positive associations for BRCA1 and BRCA2 carriers (ICC = 0.67, 95% CI: 0.52 to 0.78), whereas ER-positive associations in any one of the groups were generally inconsistent with ER-negative associations in any of the others. After stratifying by ER status in mutation carriers, additional significant associations were observed. Several previously unreported variants exhibited associations at P
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31. Aberrant transcription caused by an intronic non-canonical CDH1 variant.

Author: Bouras A, Grand-Masson C, Lefol C, Ruano E, Prieur F, and Wang Q
Published: 2024
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32. Splicing analysis of 24 potential spliceogenic variants in MMR genes and clinical interpretation based on refined ACMG/AMP criteria.

Author: Bouras A, Lefol C, Ruano E, Grand-Masson C, Auclair-Perrossier J, and Wang Q
Subjects: Humans, Germ-Line Mutation genetics, RNA Splice Sites genetics, Colorectal Neoplasms, Hereditary Nonpolyposis genetics, DNA Mismatch Repair genetics, RNA Splicing genetics
Abstract: Lynch syndrome (LS) is a common hereditary cancer syndrome caused by heterozygous germline pathogenic variants in DNA mismatch repair (MMR) genes. Splicing defect constitutes one of the major mechanisms for MMR gene inactivation. Using RT-PCR based RNA analysis, we investigated 24 potential spliceogenic variants in MMR genes and determined their pathogenicity based on refined splicing-related American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) criteria. Aberrant transcripts were confirmed in 19 variants and 17 of which were classified as pathogenic including 11 located outside of canonical splice sites. Most of these variants were previously reported in LS patients without mRNA splicing assessment. Thus, our study provides crucial evidence for pathogenicity determination, allowing for appropriate clinical follow-up. We also found that computational predictions were globally well correlated with RNA analysis results and the use of both SPiP and SpliceAI software appeared more efficient for splicing defect prediction., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
Published: 2024
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33. PMS2 or PMS2CL? Characterization of variants detected in the 3' of the PMS2 gene.

Author: Bouras A, Lefol C, Ruano E, Grand-Masson C, and Wang Q
Subjects: Humans, Mismatch Repair Endonuclease PMS2 genetics, Pseudogenes, Germ-Line Mutation, Colorectal Neoplasms genetics, Colorectal Neoplasms, Hereditary Nonpolyposis genetics
Abstract: PMS2 germline pathogenic variants are one of the major causes for Lynch syndrome and constitutional mismatch repair deficiencies. Variant identification in the 3' region of this gene is complicated by the presence of the pseudogene PMS2CL which shares a high sequence homology with PMS2. Consequently, short-fragment screening strategies (NGS, Sanger) may fail to discriminate variant's gene localization. Using a comprehensive analysis strategy, we assessed 42 NGS-detected variants in 76 patients and found 32 localized on PMS2 while 6 on PMS2CL. Interestingly, four variants were detected in either of them in different patients. Clinical phenotype was well correlated to genotype, making it very helpful in variant assessment. Our findings emphasize the necessity of more specific complementary analyses to confirm the gene origin of each variant detected in different individuals in order to avoid variant misinterpretation. In addition, we characterized two PMS2 genomic alterations involving Alu-mediated tandem duplication and gene conversion. Those mechanisms seemed to be particularly favored in PMS2 which contribute to frequent genomic rearrangements in the 3' region of the gene., (© 2023 The Authors. Genes, Chromosomes and Cancer published by Wiley Periodicals LLC.)
Published: 2024
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34. From variant of unknown significance to likely pathogenic: Characterization and pathogenicity determination of a large genomic deletion in the MLH1 gene.

Author: Bouras A, Legrand C, Kourda J, Ruano E, Grand-Masson C, Lefol C, and Wang Q
Subjects: Male, Humans, Aged, Virulence, DNA Mismatch Repair, Exons, Genomics, MutL Protein Homolog 1 genetics, Colorectal Neoplasms, Hereditary Nonpolyposis pathology
Abstract: Background: The MLH1 gene is one of the DNA mismatch repair genes (MMR), implicated in Lynch syndrome (LS), an autosomal dominant hereditary tumor susceptibility disease. The advent of next-generation sequencing (NGS) technologies has accelerated the diagnosis of inherited diseases and increased the percentage of diagnosis of inherited cancers. However, some complex genomic alterations require the combination of several analytical strategies to allow correct biological interpretations. Here, we describe a novel MLH1 deletion and its pathogenicity determination in a patient suspected of LS., Methods: The index case was a French 73-year-old man diagnosed with colorectal cancer displaying microsatellite instability and the loss of MLH1 and PMS2 expression. NGS analysis was used as the primary method for MMR genes screening. Long-range PCR and reverse transcriptase polymerase chain reaction (RT-PCR) were used for breakpoints and pathogenicity determinations., Results: A large genomic deletion was detected which removed the last six nucleotides of MLH1 exon 11 together with a large part of intron 11. It was initially considered as a variant of unknown significance (VUS). Genomic breakpoints were subsequently characterized defining the deletion as c.1033_1039-248del. Further RNA analysis demonstrated that this variant activated a cryptic donor splice site at the 5' of the breakpoint, leading to a premature truncated protein: p.Thr345Alafs*13., Conclusion: Our finding suggested that although NGS technologies have increased variant detection yield, combined approaches were still needed for complex variant characterization and pathogenicity assessment., (© 2023 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)
Published: 2023
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35. A PMS2 non-canonical splicing site variant leads to aberrant splicing in a patient suspected for lynch syndrome.

Author: Bouras A, Naibo P, Legrand C, Marc'hadour FL, Ruano E, Grand-Masson C, Lefol C, and Wang Q
Subjects: Humans, Aged, 80 and over, Mismatch Repair Endonuclease PMS2 genetics, Mismatch Repair Endonuclease PMS2 metabolism, Germ-Line Mutation, Mutation, DNA Mismatch Repair genetics, Microsatellite Instability, MutL Protein Homolog 1 genetics, Colorectal Neoplasms, Hereditary Nonpolyposis diagnosis
Abstract: The PMS2 gene is one of the DNA mismatch repair genes (MMR) implicated in Lynch syndrome (LS). A subset of PMS2 pathogenic variants (PVs) are splice variants mostly affecting canonical GT/AG splicing sequences. However, the majority of the intronic variants outside canonical splice sites remained as variants of unknown significance, even though some of them would alter the splicing process. In this report, we describe the analysis of such an intronic variant (c.251-5T > C) detected in an 82-year-old patient diagnosed with endometrial cancer displaying microsatellite instability and the loss of PMS2 expression displayed. RNA analysis demonstrated that this variant lead to the complete exon 4 skipping, resulting in the synthesis of a truncated protein. This finding shows the relevance of functional RNA analysis in the non-canonical intronic variant assessment and the importance of systematic evaluation of MSI/loss of expression of MMR genes for LS screening in patients with endometrial cancers., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)
Published: 2023
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36. The Identification of Large Rearrangements Involving Intron 2 of the CDH1 Gene in BRCA1/2 Negative and Breast Cancer Susceptibility.

Author: Ben Aissa-Haj J, Pinheiro H, Cornelis F, Sebai M, Meseure D, Briaux A, Berteaux P, Lefol C, Des Guetz G, Trassard M, Stevens D, Vialard F, Bieche I, Noguès C, Tang R, Oliveira C, Stoppat-Lyonnet D, Lidereau R, and Rouleau E
Subjects: Humans, Female, Introns genetics, DNA Copy Number Variations, Genetic Predisposition to Disease, Pedigree, BRCA1 Protein genetics, Antigens, CD genetics, Cadherins genetics, Breast Neoplasms genetics, Breast Neoplasms pathology
Abstract: E-cadherin, a CDH1 gene product, is a calcium-dependent cell-cell adhesion molecule playing a critical role in the establishment of epithelial architecture, maintenance of cell polarity, and differentiation. Germline pathogenic variants in the CDH1 gene are associated with hereditary diffuse gastric cancer (HDGC), and large rearrangements in the CDH1 gene are now being reported as well. Because CDH1 pathogenic variants could be associated with breast cancer (BC) susceptibility, CDH1 rearrangements could also impact it. The aim of our study is to identify rearrangements in the CDH1 gene in 148 BC cases with no BRCA1 and BRCA2 pathogenic variants. To do so, a zoom-in CGH array, covering the exonic, intronic, and flanking regions of the CDH1 gene, was used to screen our cohort. Intron 2 of the CDH1 gene was specifically targeted because it is largely reported to include several regulatory regions. As results, we detected one large rearrangement causing a premature stop in exon 3 of the CDH1 gene in a proband with a bilateral lobular breast carcinoma and a gastric carcinoma (GC). Two large rearrangements in the intron 2, a deletion and a duplication, were also reported only with BC cases without any familial history of GC. No germline rearrangements in the CDH1 coding region were detected in those families without GC and with a broad range of BC susceptibility. This study confirms the diversity of large rearrangements in the CDH1 gene. The rearrangements identified in intron 2 highlight the putative role of this intron in CDH1 regulation and alternative transcripts. Recurrent duplication copy number variations (CNV) are found in this region, and the deletion encompasses an alternative CDH1 transcript. Screening for large rearrangements in the CDH1 gene could be important for genetic testing of BC.
Published: 2022
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37. Acquired somatic MMR deficiency is a major cause of MSI tumor in patients suspected for "Lynch-like syndrome" including young patients.

Author: Lefol C, Sohier E, Baudet C, Naïbo P, Ruano E, Grand-Masson C, Viari A, and Wang Q
Subjects: Adenomatous Polyposis Coli Protein genetics, Adult, Aged, Colorectal Neoplasms, Hereditary Nonpolyposis diagnosis, Humans, Middle Aged, MutL Protein Homolog 1 genetics, MutS Homolog 2 Protein genetics, Colorectal Neoplasms, Hereditary Nonpolyposis genetics, DNA Mismatch Repair, Loss of Heterozygosity, Microsatellite Instability
Abstract: Patients with tumors displaying high microsatellite instability (MSI-H) but no germline MMR inactivation are suspected for Lynch-like syndrome (LLS). To explore the involvement of acquired somatic MMR alteration as a cause, we screened 113 patient tumor samples for MMR gene variations and loss of heterozygosity. Somatic MMR alterations were found in 85.8% of patients including "double hits" in 63.7% of patients, mainly diagnosed with colon and endometrial cancers. Interestingly, 37.5% of them were under the age of 50, and seven patients were under 30. Somatic alterations were mainly attributed to the MLH1, MSH2 genes, likely reflecting the functional importance of these key MMR genes. Pathogenic variants co-existed in other cancer genes in particular the APC gene displaying a characteristic MMR deficiency-related "mutational signature", indicating that it may be inactivated owing to MMR deficiency. We speculated that APC inactivation could trigger an accelerated malignant transformation underlying early-onset cancers. Our findings provide further insight into the mechanisms underlying LLS, somatic MMR inactivation being a major cause for early-onset LLS through pathways differing from those involved in late-onset sporadic cases.
Published: 2021
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38. Characterisation of heterozygous PMS2 variants in French patients with Lynch syndrome.

Author: Wang Q, Leclerc J, Bougeard G, Olschwang S, Vasseur S, Cassinari K, Boidin D, Lefol C, Naïbo P, Frébourg T, Buisine MP, and Baert-Desurmont S
Subjects: Adult, Biomarkers, Tumor genetics, Colorectal Neoplasms diagnosis, Colorectal Neoplasms pathology, Colorectal Neoplasms, Hereditary Nonpolyposis diagnosis, Colorectal Neoplasms, Hereditary Nonpolyposis pathology, DNA Methylation genetics, DNA Mismatch Repair genetics, Female, France epidemiology, Genetic Testing, Germ-Line Mutation genetics, Heterozygote, Humans, Male, Microsatellite Instability, Middle Aged, Colorectal Neoplasms genetics, Colorectal Neoplasms, Hereditary Nonpolyposis genetics, Genetic Predisposition to Disease, Mismatch Repair Endonuclease PMS2 genetics
Abstract: Background: Heterozygous germline PMS2 variants are responsible for about 5% of Lynch syndrome (LS) but their prevalence is most likely underestimated because of complicated routine screening caused by highly homologous pseudogenes. Consequently, there is limited knowledge on the implication of the PMS2 gene in LS., Methods: We report 200 PMS2 heterozygous variants identified in 195 French patients, including 112 unique variants classified as class-3/4/5., Results: Genomic rearrangements account for 18% of alterations. The c.137G>T variant was observed in 18% of the patients, but a founder effect could not be clearly identified by haplotype analysis. Among class-4/5 variant carriers, the median age at first tumour onset was 49 years with a predominance of colorectal (80%) and endometrial (8.1%) cancers. Seven patients developed colorectal cancers before the age of 30 with the youngest at the age of 21. Only 6.2% of class-4/5 carriers had a family history fulfilling Amsterdam I/II criteria among patients with available data. Tumours from PMS2 variant carriers exhibited microsatellite instability (96%) and loss of PMS2 expression (76%), confirming the high predictive value of somatic analysis., Conclusion: Our results provide further insight into the role of the PMS2 gene in LS. While PMS2 variants are mostly detected in families not fulfilling Amsterdam criteria, which supports their lower penetrance, they can nevertheless cause early-onset cancers, highlighting the variability of their penetrance., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)
Published: 2020
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39. Full in-frame exon 3 skipping of BRCA2 confers high risk of breast and/or ovarian cancer.

Author: Caputo SM, Léone M, Damiola F, Ehlen A, Carreira A, Gaidrat P, Martins A, Brandão RD, Peixoto A, Vega A, Houdayer C, Delnatte C, Bronner M, Muller D, Castera L, Guillaud-Bataille M, Søkilde I, Uhrhammer N, Demontety S, Tubeuf H, Castelain G, Jensen UB, Petitalot A, Krieger S, Lefol C, Moncoutier V, Boutry-Kryza N, Nielsen HR, Sinilnikova O, Stoppa-Lyonnet D, Spurdle AB, Teixeira MR, Coulet F, Thomassen M, and Rouleau E
Abstract: Germline pathogenic variants in the BRCA2 gene are associated with a cumulative high risk of breast/ovarian cancer. Several BRCA2 variants result in complete loss of the exon-3 at the transcript level. The pathogenicity of these variants and the functional impact of loss of exon 3 have yet to be established. As a collaboration of the COVAR clinical trial group (France), and the ENIGMA consortium for investigating breast cancer gene variants, this study evaluated 8 BRCA2 variants resulting in complete deletion of exon 3. Clinical information for 39 families was gathered from Portugal, France, Denmark and Sweden. Multifactorial likelihood analyses were conducted using information from 293 patients, for 7 out of the 8 variants (including 6 intronic). For all variants combined the likelihood ratio in favor of causality was 4.39*10 25 . These results provide convincing evidence for the pathogenicity of all examined variants that lead to a total exon 3 skipping, and suggest that other variants that result in complete loss of exon 3 at the molecular level could be associated with a high risk of cancer comparable to that associated with classical pathogenic variants in BRCA1 or BRCA2 gene. In addition, our functional study shows, for the first time, that deletion of exon 3 impairs the ability of cells to survive upon Mitomycin-C treatment, supporting lack of function for the altered BRCA2 protein in these cells. Finally, this study demonstrates that any variant leading to expression of only BRCA2 delta-exon 3 will be associated with an increased risk of breast and ovarian cancer., Competing Interests: CONFLICTS OF INTEREST All the other authors declare to have no conflicts of interest.
Published: 2018
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40. Dismantling papillary renal cell carcinoma classification: The heterogeneity of genetic profiles suggests several independent diseases.

Author: Marsaud A, Dadone B, Ambrosetti D, Baudoin C, Chamorey E, Rouleau E, Lefol C, Roussel JF, Fabas T, Cristofari G, Carpentier X, Michiels JF, Amiel J, and Pedeutour F
Subjects: Adult, Aged, Aged, 80 and over, Carcinoma, Renal Cell classification, Carcinoma, Renal Cell pathology, Chromosomes, Human, Pair 17, Chromosomes, Human, Pair 7, Female, Humans, Kidney Neoplasms pathology, Male, Middle Aged, Transcriptome, Biomarkers, Tumor metabolism, Carcinoma, Renal Cell genetics, Genetic Heterogeneity, Kidney Neoplasms genetics
Abstract: Papillary renal cell carcinoma (pRCC) is the second most frequent renal cell carcinoma (RCC) after clear cell RCC. In contrast to clear cell RCC, there is no consensual protocol using targeted therapy for metastatic pRCC. Moreover, diagnosis of some pRCC, especially pRCC of type 2 (pRCC2) may be challenging. Our aim was to identify molecular biomarkers that could be helpful for the diagnosis and treatment of pRCC. We studied the clinical, histological, immunohistological, and comprehensive genetic features of a series of 31 pRCC including 15 pRCC1 and 16 pRCC2. We aimed to determine whether pRCC represents a unique entity or several diseases. In addition, we compared the genetic features of pRCC2 to those of eight RCC showing various degrees of tubulo-papillary architecture, including three TFE-translocation RCC and five unclassified RCC. We demonstrate that pRCC is a heterogeneous group of tumors with distinct evolution. While most pRCC2 had genetic profiles similar to pRCC1, some shared genomic features, such as loss of 3p and loss of chromosome 14, with clear cell RCC, TFE-translocation RCC, and unclassified RCC. We identified variants of the MET gene in three pRCC1. A mutation in the BRAF gene was also identified in one pRCC1. In addition, using next-generation sequencing (NGS), we identified several variant genes. Genomic profiling completed by NGS allowed us to classify pRCC2 in several groups and to identify novel mutations. Our findings provide novel information on the pathogenesis of pRCC that allow insights for personalized treatment., (© 2015 Wiley Periodicals, Inc.)
Published: 2015
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41. Guidelines for splicing analysis in molecular diagnosis derived from a set of 327 combined in silico/in vitro studies on BRCA1 and BRCA2 variants.

Author: Houdayer C, Caux-Moncoutier V, Krieger S, Barrois M, Bonnet F, Bourdon V, Bronner M, Buisson M, Coulet F, Gaildrat P, Lefol C, Léone M, Mazoyer S, Muller D, Remenieras A, Révillion F, Rouleau E, Sokolowska J, Vert JP, Lidereau R, Soubrier F, Sobol H, Sevenet N, Bressac-de Paillerets B, Hardouin A, Tosi M, Sinilnikova OM, and Stoppa-Lyonnet D
Subjects: Exons genetics, Female, Humans, BRCA1 Protein genetics, BRCA2 Protein genetics, Pathology, Molecular methods, Pathology, Molecular standards, RNA Splicing genetics
Abstract: Assessing the impact of variants of unknown significance (VUS) on splicing is a key issue in molecular diagnosis. This impact can be predicted by in silico tools, but proper evaluation and user guidelines are lacking. To fill this gap, we embarked upon the largest BRCA1 and BRCA2 splice study to date by testing 272 VUSs (327 analyses) within the BRCA splice network of Unicancer. All these VUSs were analyzed by using six tools (splice site prediction by neural network, splice site finder (SSF), MaxEntScan (MES), ESE finder, relative enhancer and silencer classification by unanimous enrichment, and human splicing finder) and the predictions obtained were compared with transcript analysis results. Combining MES and SSF gave 96% sensitivity and 83% specificity for VUSs occurring in the vicinity of consensus splice sites, that is, the surrounding 11 and 14 bases for the 5' and 3' sites, respectively. This study was also an opportunity to define guidelines for transcript analysis along with a tentative classification of splice variants. The guidelines drawn from this large series should be useful for the whole community, particularly in the context of growing sequencing capacities that require robust pipelines for variant interpretation., (© 2012 Wiley Periodicals, Inc.)
Published: 2012
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42. A diagnostic genetic test for the physical mapping of germline rearrangements in the susceptibility breast cancer genes BRCA1 and BRCA2.

Author: Cheeseman K, Rouleau E, Vannier A, Thomas A, Briaux A, Lefol C, Walrafen P, Bensimon A, Lidereau R, Conseiller E, and Ceppi M
Subjects: Breast Neoplasms diagnosis, Breast Neoplasms genetics, Early Detection of Cancer, Exons, Female, Humans, Ovarian Neoplasms diagnosis, Ovarian Neoplasms genetics, Reproducibility of Results, Genes, BRCA1, Genes, BRCA2, Genetic Testing methods, Germ-Line Mutation, Physical Chromosome Mapping methods, Translocation, Genetic
Abstract: The BRCA1 and BRCA2 genes are involved in breast and ovarian cancer susceptibility. About 2 to 4% of breast cancer patients with positive family history, negative for point mutations, can be expected to carry large rearrangements in one of these two genes. We developed a novel diagnostic genetic test for the physical mapping of large rearrangements, based on molecular combing (MC), a FISH-based technique for direct visualization of single DNA molecules at high resolution. We designed specific Genomic Morse Codes (GMCs), covering the exons, the noncoding regions, and large genomic portions flanking both genes. We validated our approach by testing 10 index cases with positive family history of breast cancer and 50 negative controls. Large rearrangements, corresponding to deletions and duplications with sizes ranging from 3 to 40 kb, were detected and characterized on both genes, including four novel mutations. The nature of all the identified mutations was confirmed by high-resolution array comparative genomic hybridization (aCGH) and breakpoints characterized by sequencing. The developed GMCs allowed to localize several tandem repeat duplications on both genes. We propose the developed genetic test as a valuable tool to screen large rearrangements in BRCA1 and BRCA2 to be combined in clinical settings with an assay capable of detecting small mutations., (© 2012 Wiley Periodicals, Inc.)
Published: 2012
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43. A missense variant within BRCA1 exon 23 causing exon skipping.

Author: Rouleau E, Lefol C, Moncoutier V, Castera L, Houdayer C, Caputo S, Bièche I, Buisson M, Mazoyer S, Stoppa-Lyonnet D, Noguès C, and Lidereau R
Subjects: Adult, Base Sequence, Female, Humans, Middle Aged, Molecular Sequence Data, Nucleic Acid Denaturation genetics, Reverse Transcriptase Polymerase Chain Reaction, BRCA1 Protein genetics, Exons genetics, Mutation, Missense genetics
Published: 2010
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44. A one-step prescreening for point mutations and large rearrangement in BRCA1 and BRCA2 genes using quantitative polymerase chain reaction and high-resolution melting curve analysis.

Author: Coulet F, Pires F, Rouleau E, Lefol C, Martin S, Colas C, Cohen-Haguenauer O, Giurgea I, Fajac A, Noguès C, Demange L, Hardouin A, Lidereau R, and Soubrier F
Subjects: Alleles, Breast Neoplasms genetics, Chromatography, High Pressure Liquid, Comparative Genomic Hybridization, Computer Systems, DNA Primers, Female, Fluorometry methods, Humans, Mutagenesis, Insertional, Prospective Studies, Retrospective Studies, Sensitivity and Specificity, Sequence Analysis, DNA, Genes, BRCA1, Genes, BRCA2, Genetic Testing methods, Nucleic Acid Denaturation, Point Mutation, Polymerase Chain Reaction methods
Abstract: High-resolution melting (HRM) of DNA is a versatile method for mutation scanning that monitors the fluorescence of double-strand DNA with saturating dye. Performing HRM on a real-time thermocycler enables semiquantitative analysis (quantitative polymerase chain reaction, qPCR) to be associated to HRM analysis for detection of both large gene rearrangements and point mutations (qPCR-HRM). We evaluated this method of mutation screening for the two major breast and ovarian cancer susceptibility genes BRCA1 and BRCA2. Screening of these two genes is time-consuming and must include exploration of large rearrangements that represent 5% to 15% of the alterations observed in these genes. To assess the reliability of the HRM technology, 201 known nucleotide variations scattered over all amplicons were tested. The sensitivity of qPCR was evaluated by analyzing seven large rearrangements. All previously identified variants tested were detected by qPCR-HRM. A retrospective study was done with 45 patients: qPCR-HRM allowed all the variants previously tested by denaturing high-performance liquid chromatography to be identified. qPCR analysis showed three cases of allele dropout (due to a 104-bp deletion, SNP primer mismatch, and an Alu insertion). A prospective study was done with 165 patients allowing 22 deleterious mutations, 16 unclassified variants, and 2 rearrangements to be detected. qPCR-HRM is a simple, sensitive, and fast method that does not require modified PCR primers. Thus, this method allows in one step the detection of point mutation, gene rearrangements, and prevention of missing a mutation due to primer mismatch.
Published: 2010
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45. Quantitative PCR high-resolution melting (qPCR-HRM) curve analysis, a new approach to simultaneously screen point mutations and large rearrangements: application to MLH1 germline mutations in Lynch syndrome.

Author: Rouleau E, Lefol C, Bourdon V, Coulet F, Noguchi T, Soubrier F, Bièche I, Olschwang S, Sobol H, and Lidereau R
Subjects: DNA Primers metabolism, Exons genetics, Gene Rearrangement, Humans, MutL Protein Homolog 1, Nucleic Acid Hybridization, Reference Standards, Adaptor Proteins, Signal Transducing genetics, Colorectal Neoplasms, Hereditary Nonpolyposis genetics, DNA Mutational Analysis methods, Germ-Line Mutation genetics, Nuclear Proteins genetics, Nucleic Acid Denaturation, Point Mutation genetics, Polymerase Chain Reaction methods
Abstract: Several techniques have been developed to screen mismatch repair (MMR) genes for deleterious mutations. Until now, two different techniques were required to screen for both point mutations and large rearrangements. For the first time, we propose a new approach, called "quantitative PCR (qPCR) high-resolution melting (HRM) curve analysis (qPCR-HRM)," which combines qPCR and HRM to obtain a rapid and cost-effective method suitable for testing a large series of samples. We designed PCR amplicons to scan the MLH1 gene using qPCR HRM. Seventy-six patients were fully scanned in replicate, including 14 wild-type patients and 62 patients with known mutations (57 point mutations and five rearrangements). To validate the detected mutations, we used sequencing and/or hybridization on a dedicated MLH1 array-comparative genomic hybridization (array-CGH). All point mutations and rearrangements detected by denaturing high-performance liquid chromatography (dHPLC)+multiplex ligation-dependent probe amplification (MLPA) were successfully detected by qPCR HRM. Three large rearrangements were characterized with the dedicated MLH1 array-CGH. One variant was detected with qPCR HRM in a wild-type patient and was located within the reverse primer. One variant was not detected with qPCR HRM or with dHPLC due to its proximity to a T-stretch. With qPCR HRM, prescreening for point mutations and large rearrangements are performed in one tube and in one step with a single machine, without the need for any automated sequencer in the prescreening process. In replicate, its reagent cost, sensitivity, and specificity are comparable to those of dHPLC+MLPA techniques. However, qPCR HRM outperformed the other techniques in terms of its rapidity and amount of data provided.
Published: 2009
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