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1. Beating Versus Arrested Heart Isolated Tricuspid Valve Surgery: Long-term Outcomes

Author

Russo, M, Di Mauro, M, Saitto, G, Lio, A, Berretta, P, Taramasso, M, Scrofani, R, Della Corte, A, Sponga, S, Greco, E, Saccocci, M, Calafiore, A, Bianchi, G, Leviner, D, Biondi, A, Della Ratta, E, Livi, U, Sharoni, E, Werner, P, De Vincentiis, C, Di Eusanio, M, Kocher, A, Antona, C, Miraldi, F, Troise, G, Solinas, M, Maisano, F, Laufer, G, Musumeci, F, Andreas, M, Russo M., Di Mauro M., Saitto G., Lio A., Berretta P., Taramasso M., Scrofani R., Della Corte A., Sponga S., Greco E., Saccocci M., Calafiore A., Bianchi G., Leviner D. B., Biondi A., Della Ratta E., Livi U., Sharoni E., Werner P., De Vincentiis C., Di Eusanio M., Kocher A., Antona C., Miraldi F., Troise G., Solinas M., Maisano F., Laufer G., Musumeci F., Andreas M., Russo, M, Di Mauro, M, Saitto, G, Lio, A, Berretta, P, Taramasso, M, Scrofani, R, Della Corte, A, Sponga, S, Greco, E, Saccocci, M, Calafiore, A, Bianchi, G, Leviner, D, Biondi, A, Della Ratta, E, Livi, U, Sharoni, E, Werner, P, De Vincentiis, C, Di Eusanio, M, Kocher, A, Antona, C, Miraldi, F, Troise, G, Solinas, M, Maisano, F, Laufer, G, Musumeci, F, Andreas, M, Russo M., Di Mauro M., Saitto G., Lio A., Berretta P., Taramasso M., Scrofani R., Della Corte A., Sponga S., Greco E., Saccocci M., Calafiore A., Bianchi G., Leviner D. B., Biondi A., Della Ratta E., Livi U., Sharoni E., Werner P., De Vincentiis C., Di Eusanio M., Kocher A., Antona C., Miraldi F., Troise G., Solinas M., Maisano F., Laufer G., Musumeci F., and Andreas M.

Abstract

Background: Isolated tricuspid valve (TV) surgery is a rare procedure generally considered at high risk for perioperative mortality and poor long-term outcomes. Surgical treatment can be performed with either an arrested heart (AH) or beating heart (BH) technique. The aim of this study was to compare the outcomes of isolated tricuspid surgery with 2 different approaches. Methods: The Surgical-Tricuspid Study is a multicenter international retrospective study enrolling adult patients who underwent isolated TV procedures (n = 406; age 56 ± 16 years; 56% female) at 13 international sites. The AH and BH strategies were performed in 253 and 153 patients, respectively. Propensity score-matched analysis was used to compare groups. Results: After matching, 129 pairs were obtained and analyzed. The 30-day mortality rate was 6.2% versus 5.0% in the AH and BH groups, respectively (P = .9). The rates of acute renal failure requiring replacement therapy (10% versus 3%; P = .02) and stroke (1.6% versus 0%; P = .08) were numerically higher in the AH group. The 6-year survival rate was 67% ± 6% versus 78% ± 5% in the AH and BH groups, respectively (P = .18), whereas freedom from cardiac death was 75% ± 5% versus 84% ± 4% (P = .21). The 6-year composite cardiac end point of cardiac death and reoperation rate was 60% ± 9% versus 86% ± 5% (P = .024) comparing AH-TV replacement and BH-TV repair groups. Conclusions: Isolated TV surgery performed with a BH strategy is a safe option and resulted in a trend of increased long-term survival and freedom from reoperation compared with the standard AH technique. Patients undergoing BH valve repair had the best long-term outcome.

Published
2022

2. Genomic and immune landscape Of metastatic pheochromocytoma and paraganglioma.

Author

Calsina, B., Piñeiro-Yáñez, E., Martínez-Montes, Á.M., Caleiras, E., Fernández-Sanromán, Á., Monteagudo, M., Torres-Pérez, R., Fustero-Torre, C., Pulgarín-Alfaro, M., Gil, E., Letón, R., Jiménez, S., García-Martín, S., Martin, M.C., Roldán-Romero, J.M., Lanillos, J., Mellid, S., Santos, M., Díaz-Talavera, A., Rubio, Á., González, P., Hernando, B., Bechmann, N., Dona, M.A., Calatayud, M., Guadalix, S., Álvarez-Escolá, C., Regojo, R.M., Aller, J., Olmo-Garcia, M.I. Del, López-Fernández, A., Fliedner, S.M., Rapizzi, E., Fassnacht, M., Beuschlein, F., Quinkler, M., Toledo, R.A., Mannelli, M., Timmers, H.J., Eisenhofer, G., Rodríguez-Perales, S., Domínguez, O., Macintyre, G., Currás-Freixes, M., Rodríguez-Antona, C., Cascón, A., Leandro-García, L.J., Montero-Conde, C., Roncador, G., García-García, J.F., Pacak, K., Al-Shahrour, F., Robledo, M., Calsina, B., Piñeiro-Yáñez, E., Martínez-Montes, Á.M., Caleiras, E., Fernández-Sanromán, Á., Monteagudo, M., Torres-Pérez, R., Fustero-Torre, C., Pulgarín-Alfaro, M., Gil, E., Letón, R., Jiménez, S., García-Martín, S., Martin, M.C., Roldán-Romero, J.M., Lanillos, J., Mellid, S., Santos, M., Díaz-Talavera, A., Rubio, Á., González, P., Hernando, B., Bechmann, N., Dona, M.A., Calatayud, M., Guadalix, S., Álvarez-Escolá, C., Regojo, R.M., Aller, J., Olmo-Garcia, M.I. Del, López-Fernández, A., Fliedner, S.M., Rapizzi, E., Fassnacht, M., Beuschlein, F., Quinkler, M., Toledo, R.A., Mannelli, M., Timmers, H.J., Eisenhofer, G., Rodríguez-Perales, S., Domínguez, O., Macintyre, G., Currás-Freixes, M., Rodríguez-Antona, C., Cascón, A., Leandro-García, L.J., Montero-Conde, C., Roncador, G., García-García, J.F., Pacak, K., Al-Shahrour, F., and Robledo, M.

Abstract

Item does not contain fulltext, The mechanisms triggering metastasis in pheochromocytoma/paraganglioma are unknown, hindering therapeutic options for patients with metastatic tumors (mPPGL). Herein we show by genomic profiling of a large cohort of mPPGLs that high mutational load, microsatellite instability and somatic copy-number alteration burden are associated with ATRX/TERT alterations and are suitable prognostic markers. Transcriptomic analysis defines the signaling networks involved in the acquisition of metastatic competence and establishes a gene signature related to mPPGLs, highlighting CDK1 as an additional mPPGL marker. Immunogenomics accompanied by immunohistochemistry identifies a heterogeneous ecosystem at the tumor microenvironment level, linked to the genomic subtype and tumor behavior. Specifically, we define a general immunosuppressive microenvironment in mPPGLs, the exception being PD-L1 expressing MAML3-related tumors. Our study reveals canonical markers for risk of metastasis, and suggests the usefulness of including immune parameters in clinical management for PPGL prognostication and identification of patients who might benefit from immunotherapy.

Published
2023

3. CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study

Author

Kang, E-Y, Weir, A, Meagher, NS, Farrington, K, Nelson, GS, Ghatage, P, Lee, C-H, Riggan, MJ, Bolithon, A, Popovic, G, Leung, B, Tang, K, Lambie, N, Millstein, J, Alsop, J, Anglesio, MS, Ataseven, B, Barlow, E, Beckmann, MW, Berger, J, Bisinotto, C, Boesmueller, H, Boros, J, Brand, AH, Brooks-Wilson, A, Brucker, SY, Carney, ME, Casablanca, Y, Cazorla-Jimenez, A, Cohen, PA, Conrads, TP, Cook, LS, Coulson, P, Courtney-Brooks, M, Cramer, DW, Crowe, P, Cunningham, JM, Cybulski, C, Darcy, KM, El-Bahrawy, MA, Elishaev, E, Erber, R, Farrell, R, Fereday, S, Fischer, A, Garcia, MJ, Gayther, SA, Gentry-Maharaj, A, Gilks, CB, Grube, M, Harnett, PR, Harrington, SP, Harter, P, Hartmann, A, Hecht, JL, Heikaus, S, Hein, A, Heitz, F, Hendley, J, Hernandez, BY, Hernando Polo, S, Heublein, S, Hirasawa, A, Hogdall, E, Hogdall, CK, Horlings, HM, Huntsman, DG, Huzarski, T, Jewell, A, Jimenez-Linan, M, Jones, ME, Kaufmann, SH, Kennedy, CJ, Khabele, D, Kommoss, FKF, Kruitwagen, RFPM, Lambrechts, D, Le, ND, Lener, M, Lester, J, Leung, Y, Linder, A, Loverix, L, Lubinski, J, Madan, R, Maxwell, GL, Modugno, F, Neuhausen, SL, Olawaiye, A, Olbrecht, S, Orsulic, S, Palacios, J, Pearce, CL, Pike, MC, Quinn, CM, Mohan, GR, Rodriguez-Antona, C, Ruebner, M, Ryan, A, Salfinger, SG, Sasamoto, N, Schildkraut, JM, Schoemaker, MJ, Shah, M, Sharma, R, Shvetsov, YB, Singh, N, Sonke, GS, Steele, L, Stewart, CJR, Sundfeldt, K, Swerdlow, AJ, Talhouk, A, Tan, A, Taylor, SE, Terry, KL, Toloczko, A, Traficante, N, Van de Vijver, KK, van der Aa, MA, Van Gorp, T, Van Nieuwenhuysen, E, Van-Wagensveld, L, Vergote, I, Vierkant, RA, Wang, C, Wilkens, LR, Winham, SJ, Wu, AH, Benitez, J, Berchuck, A, Candido Dos Reis, FJ, DeFazio, A, Fasching, PA, Goode, EL, Goodman, MT, Gronwald, J, Karlan, BY, Kommoss, S, Menon, U, Sinn, H-P, Staebler, A, Brenton, JD, Bowtell, DD, Pharoah, PDP, Ramus, SJ, Kobel, M, Kang, E-Y, Weir, A, Meagher, NS, Farrington, K, Nelson, GS, Ghatage, P, Lee, C-H, Riggan, MJ, Bolithon, A, Popovic, G, Leung, B, Tang, K, Lambie, N, Millstein, J, Alsop, J, Anglesio, MS, Ataseven, B, Barlow, E, Beckmann, MW, Berger, J, Bisinotto, C, Boesmueller, H, Boros, J, Brand, AH, Brooks-Wilson, A, Brucker, SY, Carney, ME, Casablanca, Y, Cazorla-Jimenez, A, Cohen, PA, Conrads, TP, Cook, LS, Coulson, P, Courtney-Brooks, M, Cramer, DW, Crowe, P, Cunningham, JM, Cybulski, C, Darcy, KM, El-Bahrawy, MA, Elishaev, E, Erber, R, Farrell, R, Fereday, S, Fischer, A, Garcia, MJ, Gayther, SA, Gentry-Maharaj, A, Gilks, CB, Grube, M, Harnett, PR, Harrington, SP, Harter, P, Hartmann, A, Hecht, JL, Heikaus, S, Hein, A, Heitz, F, Hendley, J, Hernandez, BY, Hernando Polo, S, Heublein, S, Hirasawa, A, Hogdall, E, Hogdall, CK, Horlings, HM, Huntsman, DG, Huzarski, T, Jewell, A, Jimenez-Linan, M, Jones, ME, Kaufmann, SH, Kennedy, CJ, Khabele, D, Kommoss, FKF, Kruitwagen, RFPM, Lambrechts, D, Le, ND, Lener, M, Lester, J, Leung, Y, Linder, A, Loverix, L, Lubinski, J, Madan, R, Maxwell, GL, Modugno, F, Neuhausen, SL, Olawaiye, A, Olbrecht, S, Orsulic, S, Palacios, J, Pearce, CL, Pike, MC, Quinn, CM, Mohan, GR, Rodriguez-Antona, C, Ruebner, M, Ryan, A, Salfinger, SG, Sasamoto, N, Schildkraut, JM, Schoemaker, MJ, Shah, M, Sharma, R, Shvetsov, YB, Singh, N, Sonke, GS, Steele, L, Stewart, CJR, Sundfeldt, K, Swerdlow, AJ, Talhouk, A, Tan, A, Taylor, SE, Terry, KL, Toloczko, A, Traficante, N, Van de Vijver, KK, van der Aa, MA, Van Gorp, T, Van Nieuwenhuysen, E, Van-Wagensveld, L, Vergote, I, Vierkant, RA, Wang, C, Wilkens, LR, Winham, SJ, Wu, AH, Benitez, J, Berchuck, A, Candido Dos Reis, FJ, DeFazio, A, Fasching, PA, Goode, EL, Goodman, MT, Gronwald, J, Karlan, BY, Kommoss, S, Menon, U, Sinn, H-P, Staebler, A, Brenton, JD, Bowtell, DD, Pharoah, PDP, Ramus, SJ, and Kobel, M

Abstract

BACKGROUND: Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC. METHODS: Within the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated. RESULTS: High-level amplification (>8 copies by chromogenic in situ hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found in 22.4%. CCNE1 high-level amplification and overexpression both were linked to shorter overall survival in multivariate survival analysis adjusted for age and stage, with hazard stratification by study (hazard ratio [HR], 1.26; 95% CI, 1.08-1.47, p = .034, and HR, 1.18; 95% CI, 1.05-1.32, p = .015, respectively). This was also true for cases with combined high-level amplification/overexpression (HR, 1.26; 95% CI, 1.09-1.47, p = .033). CCNE1 mRNA expression was not associated with overall survival (HR, 1.00 per 1-SD increase; 95% CI, 0.94-1.06; p = .58). CCNE1 high-level amplification is mutually exclusive with the presence of germline BRCA1/2 pathogenic variants and shows an inverse association to RB1 loss. CONCLUSION: This study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC.

Published
2023

13. OC09 CLINICAL AND HEMODYNAMIC OUTCOMES AFTER AORTIC VALVE REPLACEMENT WITH RAPID-DEPLOYMENT BIOPROSTHESES: RESULTS FROM AN ITALIAN NATIONAL REGISTRY

Author

D’Onofrio, A., Tessari, C., Filippini, C., Diena, M., Solinas, M., Alamanni, F., Massetti, M., Livi, U., Di Eusanio, M., Mignosa, C., Russo, C., Rinaldi, M., Di Bartolomeo, R., Luzi, G., Antona, C., De Paulis, R., Salvador, L., Maselli, D., Portoghese, M., Alfieri, O., De Filippo, C.M., Bortolotti, U., Musumeci, F., and Gerosa, G.

Published
2018
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15. OC21 EARLY OUTCOMES OF MINIMALLY INVASIVE AORTIC VALVE REPLACEMENT WITH RAPID DEPLOYMENT BIOPROSTHESES: INSIGHTS FROM AN ITALIAN NATIONAL REGISTRY.

Author

Tessari, C., D’Onofrio, A., Diena, M., Solinas, M., Alamanni, F., Massetti, M., Livi, U., Di Eusanio, M., Mignosa, C., Russo, C., Rinaldi, M., Di Bartolomeo, R., Luzi, G., Antona, C., De Paulis, R., Salvador, L., Maselli, D., Portoghese, M., Alfieri, O., De Filippo, C.M., Bortolotti, U., Musumeci, F., and Gerosa, G.

Published
2018
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16. OC69 SURGERY FOR BENTALL ENDOCARDITIS: SHORT AND LONG-TERM OUTCOME FROM A MULTI-CENTRE REGISTRY

Author

Sponga, S., Di Mauro, M., Pacini, D., Murara, G., Di Bartolomeo, R., Cappabianca, G., Beghi, C., Weltert, L., De Paulis, R., De Vincentiis, C., Biondi, A., Santini, F., Salsano, A., Salvador, L., Picichè, M., Mariscalco, G., Maselli, D., Rinaldi, M., Mancuso, S., Scrofani, R., Cagnoni, G., Antona, C., Dato, G.M.A., Centofani, P., De Bonis, M., Pozzoli, A., Cugola, D., Galletti, L., Villa, E., Dossena, Y., Troise, G., Barili, F., Paparella, D., Margari, V., Lorusso, R., Parolari, A., and Livi, U.

Published
2018
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17. OC71 SURGICAL TREATMENT FOR ISOLATED TRICUSPID VALVE INFECTIVE ENDOCARDITIS. 25-YEAR RESULTS

Author

Di Mauro, M., Dato, G. Actis, Barili, F., Corte, A. Della, Ratta, E. Della, Cugola, D., Galletti, L., Centofanti, P., Santini, F., Salsano, A., Rinaldi, M., Mancuso, S., Cappabianca, G., Beghi, C., De Vincentiis, C., Biondi, A., Livi, U., Sponga, S., Pacini, D., Murara, G., Di Bortalomeo, R., Scrofani, R., Cagnoni, G., Antona, C., Nicolini, F., Benassi, F., De Bonis, M., Pozzoli, A., Casali, G., Scrascia, G., Bortolotti, U., Falcetta, G., Musumeci, F., Gherli, R., Vizzardi, E., Salvador, L., Piccichè, M., Paparella, D., Margari, V., Troise, G., Villa, E., Dossena, Y., Lucarelli, C., Onorati, F., Faggian, G., Mariscalco, G., Maselli, D., Foschi, M., Parolari, A., and Lorusso, R.

Published
2018
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19. Polygenic risk modeling for prediction of epithelial ovarian cancer risk (vol 30, pg 349, 2021)

Author

Dareng, EO, Tyrer, JP, Barnes, DR, Jones, MR, Yang, X, Aben, KKH, Adank, MA, Agata, S, Andrulis, IL, Anton-Culver, H, Antonenkova, NN, Aravantinos, G, Arun, BK, Augustinsson, A, Balmana, J, Bandera, EV, Barkardottir, RB, Barrowdale, D, Beckmann, MW, Beeghly-Fadiel, A, Benitez, J, Bermisheva, M, Bernardini, MQ, Bjorge, L, Black, A, Bogdanova, NV, Bonanni, B, Borg, A, Brenton, JD, Budzilowska, A, Butzow, R, Buys, SS, Cai, H, Caligo, MA, Campbell, I, Cannioto, R, Cassingham, H, Chang-Claude, J, Chanock, SJ, Chen, K, Chiew, Y-E, Chung, WK, Claes, KBM, Colonna, S, Cook, LS, Couch, FJ, Daly, MB, Dao, F, Davies, E, de la Hoya, M, de Putter, R, Dennis, J, DePersia, A, Devilee, P, Diez, O, Ding, YC, Doherty, JA, Domchek, SM, Dork, T, du Bois, A, Durst, M, Eccles, DM, Eliassen, HA, Engel, C, Evans, GD, Fasching, PA, Flanagan, JM, Fortner, RT, Machackova, E, Friedman, E, Ganz, PA, Garber, J, Gensini, F, Giles, GG, Glendon, G, Godwin, AK, Goodman, MT, Greene, MH, Gronwald, J, Hahnen, E, Haiman, CA, Hakansson, N, Hamann, U, Hansen, TVO, Harris, HR, Hartman, M, Heitz, F, Hildebrandt, MAT, Hogdall, E, Hogdall, CK, Hopper, JL, Huang, R-Y, Huff, C, Hulick, PJ, Huntsman, DG, Imyanitov, EN, Isaacs, C, Jakubowska, A, James, PA, Janavicius, R, Jensen, A, Johannsson, OT, John, EM, Jones, ME, Kang, D, Karlan, BY, Karnezis, A, Kelemen, LE, Khusnutdinova, E, Kiemeney, LA, Kim, B-G, Kjaer, SK, Komenaka, I, Kupryjanczyk, J, Kurian, AW, Kwong, A, Lambrechts, D, Larson, MC, Lazaro, C, Le, ND, Leslie, G, Lester, J, Lesueur, F, Levine, DA, Li, L, Li, J, Loud, JT, Lu, KH, Lubinski, J, Mai, PL, Manoukian, S, Marks, JR, Matsuno, RK, Matsuo, K, May, T, McGuffog, L, McLaughlin, JR, McNeish, IA, Mebirouk, N, Menon, U, Miller, A, Milne, RL, Minlikeeva, A, Modugno, F, Montagna, M, Moysich, KB, Munro, E, Nathanson, KL, Neuhausen, SL, Nevanlinna, H, Yie, JNY, Nielsen, HR, Nielsen, FC, Nikitina-Zake, L, Odunsi, K, Offit, K, Olah, E, Olbrecht, S, Olopade, OI, Olson, SH, Olsson, H, Osorio, A, Papi, L, Park, SK, Parsons, MT, Pathak, H, Pedersen, IS, Peixoto, A, Pejovic, T, Perez-Segura, P, Permuth, JB, Peshkin, B, Peterlongo, P, Piskorz, A, Prokofyeva, D, Radice, P, Rantala, J, Riggan, MJ, Risch, HA, Rodriguez-Antona, C, Ross, E, Rossing, MA, Runnebaum, I, Sandler, DP, Santamarina, M, Soucy, P, Schmutzler, RK, Setiawan, VW, Shan, K, Sieh, W, Simard, J, Singer, CF, Sokolenko, AP, Song, H, Southey, MC, Steed, H, Stoppa-Lyonnet, D, Sutphen, R, Swerdlow, AJ, Tan, YY, Teixeira, MR, Teo, SH, Terry, KL, Terry, MB, Thomassen, M, Thompson, PJ, Thomsen, LCV, Thull, DL, Tischkowitz, M, Titus, L, Toland, AE, Torres, D, Trabert, B, Travis, R, Tung, N, Tworoger, SS, Valen, E, van Altena, AM, van der Hout, AH, Van Nieuwenhuysen, E, van Rensburg, EJ, Vega, A, Edwards, DV, Vierkant, RA, Wang, F, Wappenschmidt, B, Webb, PM, Weinberg, CR, Weitzel, JN, Wentzensen, N, White, E, Whittemore, AS, Winham, SJ, Wolk, A, Woo, Y-L, Wu, AH, Yan, L, Yannoukakos, D, Zavaglia, KM, Zheng, W, Ziogas, A, Zorn, KK, Kleibl, Z, Easton, D, Lawrenson, K, DeFazio, A, Sellers, TA, Ramus, SJ, Pearce, CL, Monteiro, AN, Cunningham, JM, Goode, EL, Schildkraut, JM, Berchuck, A, Chenevix-Trench, G, Gayther, SA, Antoniou, AC, Pharoah, PDP, Dareng, EO, Tyrer, JP, Barnes, DR, Jones, MR, Yang, X, Aben, KKH, Adank, MA, Agata, S, Andrulis, IL, Anton-Culver, H, Antonenkova, NN, Aravantinos, G, Arun, BK, Augustinsson, A, Balmana, J, Bandera, EV, Barkardottir, RB, Barrowdale, D, Beckmann, MW, Beeghly-Fadiel, A, Benitez, J, Bermisheva, M, Bernardini, MQ, Bjorge, L, Black, A, Bogdanova, NV, Bonanni, B, Borg, A, Brenton, JD, Budzilowska, A, Butzow, R, Buys, SS, Cai, H, Caligo, MA, Campbell, I, Cannioto, R, Cassingham, H, Chang-Claude, J, Chanock, SJ, Chen, K, Chiew, Y-E, Chung, WK, Claes, KBM, Colonna, S, Cook, LS, Couch, FJ, Daly, MB, Dao, F, Davies, E, de la Hoya, M, de Putter, R, Dennis, J, DePersia, A, Devilee, P, Diez, O, Ding, YC, Doherty, JA, Domchek, SM, Dork, T, du Bois, A, Durst, M, Eccles, DM, Eliassen, HA, Engel, C, Evans, GD, Fasching, PA, Flanagan, JM, Fortner, RT, Machackova, E, Friedman, E, Ganz, PA, Garber, J, Gensini, F, Giles, GG, Glendon, G, Godwin, AK, Goodman, MT, Greene, MH, Gronwald, J, Hahnen, E, Haiman, CA, Hakansson, N, Hamann, U, Hansen, TVO, Harris, HR, Hartman, M, Heitz, F, Hildebrandt, MAT, Hogdall, E, Hogdall, CK, Hopper, JL, Huang, R-Y, Huff, C, Hulick, PJ, Huntsman, DG, Imyanitov, EN, Isaacs, C, Jakubowska, A, James, PA, Janavicius, R, Jensen, A, Johannsson, OT, John, EM, Jones, ME, Kang, D, Karlan, BY, Karnezis, A, Kelemen, LE, Khusnutdinova, E, Kiemeney, LA, Kim, B-G, Kjaer, SK, Komenaka, I, Kupryjanczyk, J, Kurian, AW, Kwong, A, Lambrechts, D, Larson, MC, Lazaro, C, Le, ND, Leslie, G, Lester, J, Lesueur, F, Levine, DA, Li, L, Li, J, Loud, JT, Lu, KH, Lubinski, J, Mai, PL, Manoukian, S, Marks, JR, Matsuno, RK, Matsuo, K, May, T, McGuffog, L, McLaughlin, JR, McNeish, IA, Mebirouk, N, Menon, U, Miller, A, Milne, RL, Minlikeeva, A, Modugno, F, Montagna, M, Moysich, KB, Munro, E, Nathanson, KL, Neuhausen, SL, Nevanlinna, H, Yie, JNY, Nielsen, HR, Nielsen, FC, Nikitina-Zake, L, Odunsi, K, Offit, K, Olah, E, Olbrecht, S, Olopade, OI, Olson, SH, Olsson, H, Osorio, A, Papi, L, Park, SK, Parsons, MT, Pathak, H, Pedersen, IS, Peixoto, A, Pejovic, T, Perez-Segura, P, Permuth, JB, Peshkin, B, Peterlongo, P, Piskorz, A, Prokofyeva, D, Radice, P, Rantala, J, Riggan, MJ, Risch, HA, Rodriguez-Antona, C, Ross, E, Rossing, MA, Runnebaum, I, Sandler, DP, Santamarina, M, Soucy, P, Schmutzler, RK, Setiawan, VW, Shan, K, Sieh, W, Simard, J, Singer, CF, Sokolenko, AP, Song, H, Southey, MC, Steed, H, Stoppa-Lyonnet, D, Sutphen, R, Swerdlow, AJ, Tan, YY, Teixeira, MR, Teo, SH, Terry, KL, Terry, MB, Thomassen, M, Thompson, PJ, Thomsen, LCV, Thull, DL, Tischkowitz, M, Titus, L, Toland, AE, Torres, D, Trabert, B, Travis, R, Tung, N, Tworoger, SS, Valen, E, van Altena, AM, van der Hout, AH, Van Nieuwenhuysen, E, van Rensburg, EJ, Vega, A, Edwards, DV, Vierkant, RA, Wang, F, Wappenschmidt, B, Webb, PM, Weinberg, CR, Weitzel, JN, Wentzensen, N, White, E, Whittemore, AS, Winham, SJ, Wolk, A, Woo, Y-L, Wu, AH, Yan, L, Yannoukakos, D, Zavaglia, KM, Zheng, W, Ziogas, A, Zorn, KK, Kleibl, Z, Easton, D, Lawrenson, K, DeFazio, A, Sellers, TA, Ramus, SJ, Pearce, CL, Monteiro, AN, Cunningham, JM, Goode, EL, Schildkraut, JM, Berchuck, A, Chenevix-Trench, G, Gayther, SA, Antoniou, AC, and Pharoah, PDP

Published
2022

20. Polygenic risk modeling for prediction of epithelial ovarian cancer risk

Author

Dareng, EO, Tyrer, JP, Barnes, DR, Jones, MR, Yang, X, Aben, KKH, Adank, MA, Agata, S, Andrulis, IL, Anton-Culver, H, Antonenkova, NN, Aravantinos, G, Arun, BK, Augustinsson, A, Balmana, J, Bandera, E, Barkardottir, RB, Barrowdale, D, Beckmann, MW, Beeghly-Fadiel, A, Benitez, J, Bermisheva, M, Bernardini, MQ, Bjorge, L, Black, A, Bogdanova, N, Bonanni, B, Borg, A, Brenton, JD, Budzilowska, A, Butzow, R, Buys, SS, Cai, H, Caligo, MA, Campbell, I, Cannioto, R, Cassingham, H, Chang-Claude, J, Chanock, SJ, Chen, K, Chiew, Y-E, Chung, WK, Claes, KBM, Colonna, S, Cook, LS, Couch, FJ, Daly, MB, Dao, F, Davies, E, de la Hoya, M, de Putter, R, Dennis, J, DePersia, A, Devilee, P, Diez, O, Ding, YC, Doherty, JA, Domchek, SM, Dork, T, du Bois, A, Durst, M, Eccles, DM, Eliassen, HA, Engel, C, Evans, GD, Fasching, PA, Flanagan, JM, Fortner, R, Machackova, E, Friedman, E, Ganz, PA, Garber, J, Gensini, F, Giles, GG, Glendon, G, Godwin, AK, Goodman, MT, Greene, MH, Gronwald, J, Group, OS, AOCSGroup, Hahnen, E, Haiman, CA, Hakansson, N, Hamann, U, Hansen, TVO, Harris, HR, Hartman, M, Heitz, F, Hildebrandt, MAT, Hogdall, E, Hogdall, CK, Hopper, JL, Huang, R-Y, Huff, C, Hulick, PJ, Huntsman, DG, Imyanitov, EN, Isaacs, C, Jakubowska, A, James, PA, Janavicius, R, Jensen, A, Johannsson, OT, John, EM, Jones, ME, Kang, D, Karlan, BY, Karnezis, A, Kelemen, LE, Khusnutdinova, E, Kiemeney, LA, Kim, B-G, Kjaer, SK, Komenaka, I, Kupryjanczyk, J, Kurian, AW, Kwong, A, Lambrechts, D, Larson, MC, Lazaro, C, Le, ND, Leslie, G, Lester, J, Lesueur, F, Levine, DA, Li, L, Li, J, Loud, JT, Lu, KH, Mai, PL, Manoukian, S, Marks, JR, KimMatsuno, R, Matsuo, K, May, T, McGuffog, L, McLaughlin, JR, McNeish, IA, Mebirouk, N, Menon, U, Miller, A, Milne, RL, Minlikeeva, A, Modugno, F, Montagna, M, Moysich, KB, Munro, E, Nathanson, KL, Neuhausen, SL, Nevanlinna, H, Yie, JNY, Nielsen, HR, Nielsen, FC, Nikitina-Zake, L, Odunsi, K, Offit, K, Olah, E, Olbrecht, S, Olopade, O, Olson, SH, Olsson, H, Osorio, A, Papi, L, Park, SK, Parsons, MT, Pathak, H, Pedersen, IS, Peixoto, A, Pejovic, T, Perez-Segura, P, Permuth, JB, Peshkin, B, Peterlongo, P, Piskorz, A, Prokofyeva, D, Radice, P, Rantala, J, Riggan, MJ, Risch, HA, Rodriguez-Antona, C, Ross, E, Rossing, MA, Runnebaum, I, Sandler, DP, Santamarina, M, Soucy, P, Schmutzler, RK, Setiawan, VW, Shan, K, Sieh, W, Simard, J, Singer, CF, Sokolenko, AP, Song, H, Southey, MC, Steed, H, Stoppa-Lyonnet, D, Sutphen, R, Swerdlow, AJ, Tan, YY, Teixeira, MR, Teo, SH, Terry, KL, BethTerry, M, Thomassen, M, Thompson, PJ, Thomsen, LCV, Thull, DL, Tischkowitz, M, Titus, L, Toland, AE, Torres, D, Trabert, B, Travis, R, Tung, N, Tworoger, SS, Valen, E, van Altena, AM, van der Hout, AH, Nieuwenhuysen, E, van Rensburg, EJ, Vega, A, Edwards, DV, Vierkant, RA, Wang, F, Wappenschmidt, B, Webb, PM, Weinberg, CR, Weitzel, JN, Wentzensen, N, White, E, Whittemore, AS, Winham, SJ, Wolk, A, Woo, Y-L, Wu, AH, Yan, L, Yannoukakos, D, Zavaglia, KM, Zheng, W, Ziogas, A, Zorn, KK, Kleibl, Z, Easton, D, Lawrenson, K, DeFazio, A, Sellers, TA, Ramus, SJ, Pearce, CL, Monteiro, AN, Cunningham, J, Goode, EL, Schildkraut, JM, Berchuck, A, Chenevix-Trench, G, Gayther, SA, Antoniou, AC, Pharoah, PDP, Dareng, EO, Tyrer, JP, Barnes, DR, Jones, MR, Yang, X, Aben, KKH, Adank, MA, Agata, S, Andrulis, IL, Anton-Culver, H, Antonenkova, NN, Aravantinos, G, Arun, BK, Augustinsson, A, Balmana, J, Bandera, E, Barkardottir, RB, Barrowdale, D, Beckmann, MW, Beeghly-Fadiel, A, Benitez, J, Bermisheva, M, Bernardini, MQ, Bjorge, L, Black, A, Bogdanova, N, Bonanni, B, Borg, A, Brenton, JD, Budzilowska, A, Butzow, R, Buys, SS, Cai, H, Caligo, MA, Campbell, I, Cannioto, R, Cassingham, H, Chang-Claude, J, Chanock, SJ, Chen, K, Chiew, Y-E, Chung, WK, Claes, KBM, Colonna, S, Cook, LS, Couch, FJ, Daly, MB, Dao, F, Davies, E, de la Hoya, M, de Putter, R, Dennis, J, DePersia, A, Devilee, P, Diez, O, Ding, YC, Doherty, JA, Domchek, SM, Dork, T, du Bois, A, Durst, M, Eccles, DM, Eliassen, HA, Engel, C, Evans, GD, Fasching, PA, Flanagan, JM, Fortner, R, Machackova, E, Friedman, E, Ganz, PA, Garber, J, Gensini, F, Giles, GG, Glendon, G, Godwin, AK, Goodman, MT, Greene, MH, Gronwald, J, Group, OS, AOCSGroup, Hahnen, E, Haiman, CA, Hakansson, N, Hamann, U, Hansen, TVO, Harris, HR, Hartman, M, Heitz, F, Hildebrandt, MAT, Hogdall, E, Hogdall, CK, Hopper, JL, Huang, R-Y, Huff, C, Hulick, PJ, Huntsman, DG, Imyanitov, EN, Isaacs, C, Jakubowska, A, James, PA, Janavicius, R, Jensen, A, Johannsson, OT, John, EM, Jones, ME, Kang, D, Karlan, BY, Karnezis, A, Kelemen, LE, Khusnutdinova, E, Kiemeney, LA, Kim, B-G, Kjaer, SK, Komenaka, I, Kupryjanczyk, J, Kurian, AW, Kwong, A, Lambrechts, D, Larson, MC, Lazaro, C, Le, ND, Leslie, G, Lester, J, Lesueur, F, Levine, DA, Li, L, Li, J, Loud, JT, Lu, KH, Mai, PL, Manoukian, S, Marks, JR, KimMatsuno, R, Matsuo, K, May, T, McGuffog, L, McLaughlin, JR, McNeish, IA, Mebirouk, N, Menon, U, Miller, A, Milne, RL, Minlikeeva, A, Modugno, F, Montagna, M, Moysich, KB, Munro, E, Nathanson, KL, Neuhausen, SL, Nevanlinna, H, Yie, JNY, Nielsen, HR, Nielsen, FC, Nikitina-Zake, L, Odunsi, K, Offit, K, Olah, E, Olbrecht, S, Olopade, O, Olson, SH, Olsson, H, Osorio, A, Papi, L, Park, SK, Parsons, MT, Pathak, H, Pedersen, IS, Peixoto, A, Pejovic, T, Perez-Segura, P, Permuth, JB, Peshkin, B, Peterlongo, P, Piskorz, A, Prokofyeva, D, Radice, P, Rantala, J, Riggan, MJ, Risch, HA, Rodriguez-Antona, C, Ross, E, Rossing, MA, Runnebaum, I, Sandler, DP, Santamarina, M, Soucy, P, Schmutzler, RK, Setiawan, VW, Shan, K, Sieh, W, Simard, J, Singer, CF, Sokolenko, AP, Song, H, Southey, MC, Steed, H, Stoppa-Lyonnet, D, Sutphen, R, Swerdlow, AJ, Tan, YY, Teixeira, MR, Teo, SH, Terry, KL, BethTerry, M, Thomassen, M, Thompson, PJ, Thomsen, LCV, Thull, DL, Tischkowitz, M, Titus, L, Toland, AE, Torres, D, Trabert, B, Travis, R, Tung, N, Tworoger, SS, Valen, E, van Altena, AM, van der Hout, AH, Nieuwenhuysen, E, van Rensburg, EJ, Vega, A, Edwards, DV, Vierkant, RA, Wang, F, Wappenschmidt, B, Webb, PM, Weinberg, CR, Weitzel, JN, Wentzensen, N, White, E, Whittemore, AS, Winham, SJ, Wolk, A, Woo, Y-L, Wu, AH, Yan, L, Yannoukakos, D, Zavaglia, KM, Zheng, W, Ziogas, A, Zorn, KK, Kleibl, Z, Easton, D, Lawrenson, K, DeFazio, A, Sellers, TA, Ramus, SJ, Pearce, CL, Monteiro, AN, Cunningham, J, Goode, EL, Schildkraut, JM, Berchuck, A, Chenevix-Trench, G, Gayther, SA, Antoniou, AC, and Pharoah, PDP

Abstract

Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, "select and shrink for summary statistics" (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28-1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08-1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21-1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29-1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35-1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.

Published
2022

21. Genome-Wide Meta-Analysis Identifies Variants in DSCAM and PDLIM3 That Correlate with Efficacy Outcomes in Metastatic Renal Cell Carcinoma Patients Treated with Sunitinib

Author

Diekstra, M.H.M., Swen, J.J., Zanden, L.F.M. van der, Vermeulen, S.H., Boven, E., Mathijssen, R.H., Fukunaga, K., Mushiroda, T., Hongo, F., Oosterwijk, E., Cambon-Thomsen, A., Castellano, D., Fritsch, A., Donas, J.G., Rodriguez-Antona, C., Ruijtenbeek, R., Radu, M.T., Eisen, T., Junker, K., Roessler, M., Jaehde, U., Miki, T., Böhringer, S., Kubo, M., Kiemeney, L.A.L.M., Guchelaar, H.J., Diekstra, M.H.M., Swen, J.J., Zanden, L.F.M. van der, Vermeulen, S.H., Boven, E., Mathijssen, R.H., Fukunaga, K., Mushiroda, T., Hongo, F., Oosterwijk, E., Cambon-Thomsen, A., Castellano, D., Fritsch, A., Donas, J.G., Rodriguez-Antona, C., Ruijtenbeek, R., Radu, M.T., Eisen, T., Junker, K., Roessler, M., Jaehde, U., Miki, T., Böhringer, S., Kubo, M., Kiemeney, L.A.L.M., and Guchelaar, H.J.

Abstract

Contains fulltext : 251723.pdf (Publisher’s version ) (Open Access), Individual response to sunitinib in metastatic renal cell carcinoma (mRCC) patients is highly variable. Earlier, sunitinib outcome was related to single nucleotide polymorphisms (SNPs) in CYP3A5 and ABCB1. Our aim is to provide novel insights into biological mechanisms underlying sunitinib action. We included mRCC patients from the European EuroTARGET consortium (n = 550) and the RIKEN cohort in Japan (n = 204) which were analysed separately and in a meta-analysis of genome-wide association studies (GWAS). SNPs were tested for association with progression-free survival (PFS) and overall survival (OS) using Cox regression. Summary statistics were combined using a fixed effect meta-analysis. SNP rs28520013 in PDLIM3 and the correlated SNPs rs2205096 and rs111356738 both in DSCAM, showed genome-wide significance (p < 5 × 10(-8)) with PFS and OS in the meta-analysis. The variant T-allele of rs28520013 associated with an inferior PFS of 5.1 months compared to 12.5 months in non-carriers (p = 4.02 × 10(-10), HR = 7.26). T-allele carriers of rs28520013 showed an inferior OS of 6.9 months versus 30.2 months in non-carriers (p = 1.62 × 10(-8), HR = 5.96). In this GWAS we identified novel genetic variants in PDLIM3 and DSCAM that impact PFS and OS in mRCC patients receiving sunitinib. The underlying link between the identified genes and the molecular mechanisms of sunitinib action needs to be elucidated.

Published
2022

22. High frequency and founder effect of the CYP3A4*20 loss-of-function allele in the Spanish population classifies CYP3A4 as a polymorphic enzyme

Author

Apellániz-Ruiz, M, Inglada-Pérez, L, Naranjo, M E G, Sánchez, L, Mancikova, V, Currás-Freixes, M, de Cubas, A A, Comino-Méndez, I, Triki, S, Rebai, A, Rasool, M, Moya, G, Grazina, M, Opocher, G, Cascón, A, Taboada-Echalar, P, Ingelman-Sundberg, M, Carracedo, A, Robledo, M, Llerena, A, and Rodríguez-Antona, C

Published
2015
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25. Cabozantinib combination therapy for the treatment of solid tumors: a systematic review

Author

Castellano, D, Apolo, AB, Porta, C, Capdevila, J, Viteri, S, Rodriguez-Antona, C, Martin, L, and Maroto, P

Subjects
renal cell carcinoma, tyrosine kinase inhibitor, non-small-cell lung cancer, vascular endothelial growth factor, cabozantinib, solid tumor
Abstract

Background: Cabozantinib monotherapy is approved for the treatment of several types of solid tumors. Investigation into the use of cabozantinib combined with other therapies is increasing. To understand the evidence in this area, we performed a systematic review of cabozantinib combination therapy for the treatment of solid tumors in adults. Methods: This study was designed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses, and the protocol was registered with PROSPERO (CRD42020144680). On 9 October 2020, we searched for clinical trials and observational studies of cabozantinib as part of a combination therapy for solid tumors using Embase, MEDLINE, and Cochrane databases, and by screening relevant congress abstracts. Eligible studies reported clinical or safety outcomes, or biomarker data. Randomized and observational studies with a sample size of fewer than 25 and studies of cabozantinib monotherapy were excluded. For each study, quality was assessed using National Institute for Health and Care Excellence methodology, and the study characteristics were described qualitatively. This study was funded by Ipsen. Results: Of 2421 citations identified, 32 articles were included (6 with results from randomized studies, 24 with results from non-randomized phase I or II studies, and 2 with results from both). The most commonly studied tumor types were metastatic urothelial carcinoma/genitourinary tumors and castration-resistant prostate cancer (CRPC). Findings from randomized studies suggested that cabozantinib combined with other therapies may lead to better progression-free survival than some current standards of care in renal cell carcinoma, CRPC, and non-small-cell lung cancer. The most common adverse events were hypertension, diarrhea, and fatigue. Conclusion: This review demonstrates the promising efficacy outcomes of cabozantinib combined with other therapies, and a safety profile similar to cabozantinib alone. However, the findings are limited by the fact that most of the identified studies were reported as congress abstracts only. More evidence from randomized trials is needed to explore cabozantinib as a combination therapy further.

Published
2022

26. Surgical treatment of isolated tricuspid valve infective endocarditis: 25-year results from a multicenter registry

Author

Di Mauro, M, Foschi, M, Dato, G, Centofanti, P, Barili, F, Corte, A, Ratta, E, Cugola, D, Galletti, L, Santini, F, Salsano, A, Rinaldi, M, Mancuso, S, Cappabianca, G, Beghi, C, De Vincentiis, C, Biondi, A, Livi, U, Sponga, S, Pacini, D, Murana, G, Scrofani, R, Antona, C, Cagnoni, G, Nicolini, F, Benassi, F, De Bonis, M, Pozzoli, A, Casali, G, Scrascia, G, Falcetta, G, Bortolotti, U, Musumeci, F, Gherli, R, Vizzardi, E, Salvador, L, Piciche, M, Paparella, D, Margari, V, Troise, G, Villa, E, Dossena, Y, Lucarelli, C, Onorati, F, Faggian, G, Mariscalco, G, Maselli, D, Parolari, A, Lorusso, R, Di Mauro M., Foschi M., Dato G. M. A., Centofanti P., Barili F., Corte A. D., Ratta E. D., Cugola D., Galletti L., Santini F., Salsano A., Rinaldi M., Mancuso S., Cappabianca G., Beghi C., De Vincentiis C., Biondi A., Livi U., Sponga S., Pacini D., Murana G., Scrofani R., Antona C., Cagnoni G., Nicolini F., Benassi F., De Bonis M., Pozzoli A., Casali G., Scrascia G., Falcetta G., Bortolotti U., Musumeci F., Gherli R., Vizzardi E., Salvador L., Piciche M., Paparella D., Margari V., Troise G., Villa E., Dossena Y., Lucarelli C., Onorati F., Faggian G., Mariscalco G., Maselli D., Parolari A., Lorusso R., Di Mauro, M, Foschi, M, Dato, G, Centofanti, P, Barili, F, Corte, A, Ratta, E, Cugola, D, Galletti, L, Santini, F, Salsano, A, Rinaldi, M, Mancuso, S, Cappabianca, G, Beghi, C, De Vincentiis, C, Biondi, A, Livi, U, Sponga, S, Pacini, D, Murana, G, Scrofani, R, Antona, C, Cagnoni, G, Nicolini, F, Benassi, F, De Bonis, M, Pozzoli, A, Casali, G, Scrascia, G, Falcetta, G, Bortolotti, U, Musumeci, F, Gherli, R, Vizzardi, E, Salvador, L, Piciche, M, Paparella, D, Margari, V, Troise, G, Villa, E, Dossena, Y, Lucarelli, C, Onorati, F, Faggian, G, Mariscalco, G, Maselli, D, Parolari, A, Lorusso, R, Di Mauro M., Foschi M., Dato G. M. A., Centofanti P., Barili F., Corte A. D., Ratta E. D., Cugola D., Galletti L., Santini F., Salsano A., Rinaldi M., Mancuso S., Cappabianca G., Beghi C., De Vincentiis C., Biondi A., Livi U., Sponga S., Pacini D., Murana G., Scrofani R., Antona C., Cagnoni G., Nicolini F., Benassi F., De Bonis M., Pozzoli A., Casali G., Scrascia G., Falcetta G., Bortolotti U., Musumeci F., Gherli R., Vizzardi E., Salvador L., Piciche M., Paparella D., Margari V., Troise G., Villa E., Dossena Y., Lucarelli C., Onorati F., Faggian G., Mariscalco G., Maselli D., Parolari A., and Lorusso R.

Abstract

Background: To assess early and late mortality in patients with isolated acute tricuspid valve infective endocarditis (TVIE) using data from a multicenter registry. Methods: From 1983 to 2018, isolated acute TVIE was surgically treated in 157 (3.8%) patients [mean age 47 ± 16 years (range 15–86 years), 25% females]. Of these, 142 (90%) had native tricuspid regurgitation, 7 (5%) native tricuspid valve (TV) steno-regurgitation, and 8 (5%) prosthetic TVIE. Intravenous drug use (IVDU) was recorded in 38% of patients, infection involved cardiac implantable electronic device leads in 21%, and vascular catheters for dialysis in 1%; in the remaining cases, the cause was unknown. The primary endpoint was in-hospital outcome, long-term freedom from recurrence and overall survival. Results: Overall, 77 (49%) patients underwent TV repair, 72 (46%) TV replacement, and 8 (5%) prosthetic TV replacement. Early mortality was 11% (n = 17). Expected early mortality according to EndoSCORE was 12%, with age (odds ratio 1.06) and redo (odds ratio 6.64) as risk factors. Late deaths occurred in 31 patients and TVIE recurrences in 4. Survival rates at 10, 20, and 25 years were 66%, 60%, and 44%, respectively. Risk factors were age [hazard ratio (HR) 1.06], mycotic TVIE (HR 4.2), IVDU (HR 4.90), infected prosthesis replacement (HR 4.4), and presence of cardiac implantable electronic device leads (HR 3.0). No significant difference was found in valve repair vs. replacement and in IVDUs vs. non-IVDUs. Conclusions: Patients with isolated acute TVIE undergoing surgical treatment show acceptable early and late outcomes. TVIE recurrence was low, and repair of the affected valve does not seem to confer any advantage either at early or long term up to 25 years.

Published
2019

28. 685P Genome-wide association meta-analysis identifies novel variants that correlate with efficacy outcomes in sunitinib-treated patients with metastatic renal cell carcinoma

Author

Diekstra, M., primary, Swen, J., additional, van der Zanden, L., additional, Vermeulen, S., additional, Boven, E., additional, Mathijssen, R.H., additional, Oskarsdottir, A., additional, Oosterwijk, E., additional, Cambon-Thomsen, A., additional, Castellano, D., additional, Fritsch, A., additional, Garcia-Donas, J., additional, Rodriguez-Antona, C., additional, Jaehde, U., additional, Rafnar, T., additional, Stefansson, K., additional, Bohringer, S., additional, Kubo, M., additional, Kiemeney, L., additional, and Guchelaar, H-J., additional

Published
2021
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31. Clinical and Hemodynamic Outcomes of Rapid-Deployment Aortic Bioprostheses

Author

D'Onofrio, A., Tessari, C., Cibin, G., Lorenzoni, G., Martinelli, G. L., Solinas, M., Gerosa, G., Gregori, D., Alamanni, F., Polvani, G., Massetti, M., Eusanio, M. D., Merlo, M., Vendramin, I., Mangino, D., Mignosa, C., Russo, C., Rinaldi, M., De Paulis, R., Pacini, D., Luzi, G., Antona, C., Salvador, L., Musumeci, F., Maselli, D., Colli, A., Portoghese, M., Alfieri, O., De Filippo, C. M., Lorenzoni G., Massetti M. (ORCID:0000-0002-7100-8478), Maselli D., Portoghese M., D'Onofrio, A., Tessari, C., Cibin, G., Lorenzoni, G., Martinelli, G. L., Solinas, M., Gerosa, G., Gregori, D., Alamanni, F., Polvani, G., Massetti, M., Eusanio, M. D., Merlo, M., Vendramin, I., Mangino, D., Mignosa, C., Russo, C., Rinaldi, M., De Paulis, R., Pacini, D., Luzi, G., Antona, C., Salvador, L., Musumeci, F., Maselli, D., Colli, A., Portoghese, M., Alfieri, O., De Filippo, C. M., Lorenzoni G., Massetti M. (ORCID:0000-0002-7100-8478), Maselli D., and Portoghese M.

Abstract

Aim of this retrospective, multicenter study was to evaluate early and mid-term clinical and hemodynamic results of patients who underwent surgical aortic valve replacement (SAVR) with Intuity rapid-deployment bioprostheses (RDB) (Edwards Lifesciences, Irvine, CA). We analyzed data from the Italian Registry of Intuity Valve (INTU-ITA registry) that is a national, real-world and independent from the industry registry. Preoperative variables were defined according to EuroSCORE and postoperative outcomes according to Valve Academic Research Consortium (VARC). Survival distribution was evaluated using the Kaplan-Meier approach. A Cox-Proportional Hazard Model was employed to assess the effect of the covariates on patients’ survival. The registry included 1687 patients from 23 centers (June 2012-September 2019). Aortic cross clamp time for isolated SAVR was 55 minutes (IQR: 45–70 minute). Postoperative pace-maker rate was 6.3%. At discharge transaortic peak and mean gradients were: 18 mm Hg (IQR: 14–23 mm Hg) and 10 mmHg (IQR: 8–13 mm Hg), respectively. Indexed effective orifice area was 1.10 cm2/m2 (IQR: 0.91–1.31 cm2/m2) and the incidence of severe patient-prosthesis mismatch was 0.6%. Hemodynamic data for all valve sizes remained stable during follow-up. Thirty-day overall mortality was 1.8% (30 patients), and at follow-up it was 5.3% (89 patients). Kaplan-Meier overall survival was 95.5% (94.3–96.7%); 90.7% (88.3–93.1%); 86.4% (82.6–90.4%) at 1, 3, and 5 years, respectively. Serum creatinine (HR: 1.36; 95%CI: 1.04–1.81; p = 0.0397) and cross-clamp time (HR: 1.01; 95%CI: 1.002–1.017; p = 0.0077) were identified as independent predictors of mortality. According to our data from the INTU-ITA registry, SAVR with RDB provides good early clinical and hemodynamic results that are confirmed at follow-up.

Published
2021

32. Minimally Invasive vs Conventional Aortic Valve Replacement With Rapid-Deployment Bioprostheses

Author

D'Onofrio, A., Tessari, C., Lorenzoni, G., Cibin, G., Martinelli, G., Alamanni, F., Polvani, G., Solinas, M., Massetti, M., Merlo, M., Vendramin, I., Di Eusanio, M., Mignosa, C., Mangino, D., Russo, C., Rinaldi, M., Pacini, D., Salvador, L., Antona, C., Maselli, D., De Paulis, R., Luzi, G., Alfieri, O., De Filippo, C. M., Portoghese, M., Musumeci, F., Colli, A., Gregori, D., Gerosa, G., Lorenzoni G., Massetti M. (ORCID:0000-0002-7100-8478), Maselli D., Portoghese M., D'Onofrio, A., Tessari, C., Lorenzoni, G., Cibin, G., Martinelli, G., Alamanni, F., Polvani, G., Solinas, M., Massetti, M., Merlo, M., Vendramin, I., Di Eusanio, M., Mignosa, C., Mangino, D., Russo, C., Rinaldi, M., Pacini, D., Salvador, L., Antona, C., Maselli, D., De Paulis, R., Luzi, G., Alfieri, O., De Filippo, C. M., Portoghese, M., Musumeci, F., Colli, A., Gregori, D., Gerosa, G., Lorenzoni G., Massetti M. (ORCID:0000-0002-7100-8478), Maselli D., and Portoghese M.

Abstract

Background: The aim of this multicenter retrospective study was to compare early and midterm clinical and hemodynamic results of aortic valve replacement with rapid-deployment bioprostheses performed through conventional full-sternotomy vs mini-sternotomy. Methods: Data from the Italian multicenter registry of aortic valve replacement with rapid-deployment bioprostheses (INTU-ITA registry) were analyzed. Patients were divided into 2 groups: full sternotomy (FS) and ministernotomy (MS). Primary endpoint was the comparison of early and midterm mortality. Secondary endpoints were: comparison of intraoperative variables, complications, and hemodynamic performance. A propensity score weighting approach was used for data analysis. Results: A total of 1057 patients were analyzed: 435 (41.2%) and 622 (58.8%) in group FS and MS, respectively. Thirty-day mortality was 1.6% and 0.6% in FS and MS groups, respectively (P =.074). cardiopulmonary bypass time was 78.5 minutes and 83 minutes in FS and MS groups, respectively (P =.414). In the overall cohort, the incidence of intraoperative complications and of device success was 3.8% (40 patients) and 95.9% (1014 patients), respectively, with no significant differences between groups. Survival at 1, 3, and 5 years was 94.1%, 98.1%, 88.5% and 91.8%, 85.2%, and 84.8% in FS and MS groups, respectively (P =.412). The 2 groups showed similar postoperative gradients (median mean gradient, FS: 10.0 mm Hg, MS: 11.0 mm Hg; P =.170) and also similar incidence of patient–prosthesis mismatch (FS: 7%, MS: 6.4%, P =.647). Conclusions: According to our data, rapid-deployment bioprostheses allow the performance of minimally invasive aortic valve replacement with similar surgical times and similar clinical and hemodynamic outcomes to conventional surgery and should be considered the first choice in these procedures.

Published
2021

36. Corrigendum to “A predictive model for early mortality after surgical treatment of heart valve or prosthesis infective endocarditis. The EndoSCORE”. [Int. J. Cardiol. 241 (Aug 15 2017) 97–102](S0167527317309877)(10.1016/j.ijcard.2017.03.148)

Author

Di Mauro M., Di Mauro, M, Dato, G, Barili, F, Gelsomino, S, Sante, P, Corte, A, Carrozza, A, Ratta, E, Cugola, D, Galletti, L, Devotini, R, Casabona, R, Santini, F, Salsano, A, Scrofani, R, Antona, C, Botta, L, Russo, C, Mancuso, S, Rinaldi, M, De Vincentiis, C, Biondi, A, Beghi, C, Cappabianca, G, Tarzia, V, Gerosa, G, De Bonis, M, Pozzoli, A, Nicolini, F, Benassi, F, Rosato, F, Grasso, E, Livi, U, Sponga, S, Pacini, D, Di Bartolomeo, R, Demartino, A, Bortolotti, U, Onorati, F, Faggian, G, Lorusso, R, Vizzardi, E, Di Giammarco, G, Marinelli, D, Villa, E, Troise, G, Piciche, M, Musumeci, F, Paparella, D, Margari, V, Tritto, F, Damiani, G, Scrascia, G, Zaccaria, S, Renzulli, A, Serraino, G, Mariscalco, G, Maselli, D, Foschi, M, Parolari, A, Nappi, G, Di Mauro M., Dato G. M. A., Barili F., Gelsomino S., Sante P., Corte A. D., Carrozza A., Ratta E. D., Cugola D., Galletti L., Devotini R., Casabona R., Santini F., Salsano A., Scrofani R., Antona C., Botta L., Russo C., Mancuso S., Rinaldi M., De Vincentiis C., Biondi A., Beghi C., Cappabianca G., Tarzia V., Gerosa G., De Bonis M., Pozzoli A., Nicolini F., Benassi F., Rosato F., Grasso E., Livi U., Sponga S., Pacini D., Di Bartolomeo R., DeMartino A., Bortolotti U., Onorati F., Faggian G., Lorusso R., Vizzardi E., Di Giammarco G., Marinelli D., Villa E., Troise G., Piciche M., Musumeci F., Paparella D., Margari V., Tritto F., Damiani G., Scrascia G., Zaccaria S., Renzulli A., Serraino G., Mariscalco G., Maselli D., Foschi M., Parolari A., Nappi G., Di Mauro M., Di Mauro, M, Dato, G, Barili, F, Gelsomino, S, Sante, P, Corte, A, Carrozza, A, Ratta, E, Cugola, D, Galletti, L, Devotini, R, Casabona, R, Santini, F, Salsano, A, Scrofani, R, Antona, C, Botta, L, Russo, C, Mancuso, S, Rinaldi, M, De Vincentiis, C, Biondi, A, Beghi, C, Cappabianca, G, Tarzia, V, Gerosa, G, De Bonis, M, Pozzoli, A, Nicolini, F, Benassi, F, Rosato, F, Grasso, E, Livi, U, Sponga, S, Pacini, D, Di Bartolomeo, R, Demartino, A, Bortolotti, U, Onorati, F, Faggian, G, Lorusso, R, Vizzardi, E, Di Giammarco, G, Marinelli, D, Villa, E, Troise, G, Piciche, M, Musumeci, F, Paparella, D, Margari, V, Tritto, F, Damiani, G, Scrascia, G, Zaccaria, S, Renzulli, A, Serraino, G, Mariscalco, G, Maselli, D, Foschi, M, Parolari, A, Nappi, G, Di Mauro M., Dato G. M. A., Barili F., Gelsomino S., Sante P., Corte A. D., Carrozza A., Ratta E. D., Cugola D., Galletti L., Devotini R., Casabona R., Santini F., Salsano A., Scrofani R., Antona C., Botta L., Russo C., Mancuso S., Rinaldi M., De Vincentiis C., Biondi A., Beghi C., Cappabianca G., Tarzia V., Gerosa G., De Bonis M., Pozzoli A., Nicolini F., Benassi F., Rosato F., Grasso E., Livi U., Sponga S., Pacini D., Di Bartolomeo R., DeMartino A., Bortolotti U., Onorati F., Faggian G., Lorusso R., Vizzardi E., Di Giammarco G., Marinelli D., Villa E., Troise G., Piciche M., Musumeci F., Paparella D., Margari V., Tritto F., Damiani G., Scrascia G., Zaccaria S., Renzulli A., Serraino G., Mariscalco G., Maselli D., Foschi M., Parolari A., and Nappi G.

Abstract

The authors regret that the first name and last name of the author Sandro Sponga was published incorrectly in the original version and this has now been corrected.

Published
2018

38. Genes and variants in hematopoiesis-related pathways are associated with gemcitabine/carboplatin-induced thrombocytopenia

Author

Björn, N., Sigurgeirsson, Benjamin, Svedberg, A., Pradhananga, Sailendra, Brandén, E., Koyi, H., Lewensohn, R., de Petris, L., Apellániz-Ruiz, M., Rodríguez-Antona, C., Lundeberg, Joakim, Gréen, Henrik, Björn, N., Sigurgeirsson, Benjamin, Svedberg, A., Pradhananga, Sailendra, Brandén, E., Koyi, H., Lewensohn, R., de Petris, L., Apellániz-Ruiz, M., Rodríguez-Antona, C., Lundeberg, Joakim, and Gréen, Henrik

Abstract

Chemotherapy-induced myelosuppression, including thrombocytopenia, is a recurrent problem during cancer treatments that may require dose alterations or cessations that could affect the antitumor effect of the treatment. To identify genetic markers associated with treatment-induced thrombocytopenia, we whole-exome sequenced 215 non-small cell lung cancer patients homogeneously treated with gemcitabine/carboplatin. The decrease in platelets (defined as nadir/baseline) was used to assess treatment-induced thrombocytopenia. Association between germline genetic variants and thrombocytopenia was analyzed at single-nucleotide variant (SNV) (based on the optimal false discovery rate, the severity of predicted consequence, and effect), gene, and pathway levels. These analyses identified 130 SNVs/INDELs and 25 genes associated with thrombocytopenia (P-value < 0.002). Twenty-three SNVs were validated in an independent genome-wide association study (GWAS). The top associations include rs34491125 in JMJD1C (P-value = 9.07 × 10−5), the validated variants rs10491684 in DOCK8 (P-value = 1.95 × 10−4), rs6118 in SERPINA5 (P-value = 5.83 × 10−4), and rs5877 in SERPINC1 (P-value = 1.07 × 10−3), and the genes CAPZA2 (P-value = 4.03 × 10−4) and SERPINC1 (P-value = 1.55 × 10−3). The SNVs in the top-scoring pathway “Factors involved in megakaryocyte development and platelet production” (P-value = 3.34 × 10−4) were used to construct weighted genetic risk score (wGRS) and logistic regression models that predict thrombocytopenia. The wGRS predict which patients are at high or low toxicity risk levels, for CTCAE (odds ratio (OR) = 22.35, P-value = 1.55 × 10−8), and decrease (OR = 66.82, P-value = 5.92 × 10−9). The logistic regression models predict CTCAE grades 3–4 (receiver operator characteristics (ROC) area under the curve (AUC) = 0.79), and large decrease (ROC AUC = 0.86). We identified and validated genetic variations within hematopoiesis-related pathways that provide a solid foundatio, QC 20220412

Published
2020
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39. Clinical and pathological associations of PTEN expression in ovarian cancer: a multicentre study from the Ovarian Tumour Tissue Analysis Consortium

Author

Martins, FC, Couturier, D-L, Paterson, A, Karnezis, AN, Christine, C, Nazeran, TM, Odunsi, A, Gentry-Maharaj, A, Vrvilo, A, Hein, A, Talhouk, A, Osorio, A, Hartkopf, AD, Brooks-Wilson, A, DeFazio, A, Fischer, A, Hartmann, A, Hernandez, BY, McCauley, BM, Karpinskyj, C, de Sousa, CB, Hogdall, C, Tiezzi, DG, Herpel, E, Taran, FA, Modugno, F, Keeney, G, Nelson, G, Steed, H, Song, H, Luk, H, Benitez, J, Alsop, J, Koziak, JM, Lester, J, Rothstein, JH, de Andrade, JM, Lundvall, L, Paz-Ares, L, Robles-Diaz, L, Wilkens, LR, Garcia, MJ, Intermaggio, MP, Alcaraz, M-L, Brett, MA, Beckmann, MW, Jimenez-Linan, M, Anglesio, M, Carney, ME, Schneider, M, Traficante, N, Pejovic, N, Singh, N, Le, N, Sinn, P, Ghatage, P, Erber, R, Edwards, R, Vierkant, R, Ness, RB, Leung, S, Orsulic, S, Brucker, SY, Kaufmann, SH, Fereday, S, Gayther, S, Winham, SJ, Kommoss, S, Pejovic, T, Longacre, TA, McGuire, V, Rhenius, V, Sieh, W, Shvetsov, YB, Whittemore, AS, Staebler, A, Karlan, BY, Rodriguez-Antona, C, Bowtell, DD, Goode, EL, Hogdall, E, Candido dos Reis, FJ, Gronwald, J, Chang-Claude, J, Moysich, KB, Kelemen, LE, Cook, LS, Goodman, MT, Fasching, PA, Crawford, R, Deen, S, Menon, U, Huntsman, DG, Kobel, M, Ramus, SJ, Pharoah, PDP, Brenton, JD, Martins, FC, Couturier, D-L, Paterson, A, Karnezis, AN, Christine, C, Nazeran, TM, Odunsi, A, Gentry-Maharaj, A, Vrvilo, A, Hein, A, Talhouk, A, Osorio, A, Hartkopf, AD, Brooks-Wilson, A, DeFazio, A, Fischer, A, Hartmann, A, Hernandez, BY, McCauley, BM, Karpinskyj, C, de Sousa, CB, Hogdall, C, Tiezzi, DG, Herpel, E, Taran, FA, Modugno, F, Keeney, G, Nelson, G, Steed, H, Song, H, Luk, H, Benitez, J, Alsop, J, Koziak, JM, Lester, J, Rothstein, JH, de Andrade, JM, Lundvall, L, Paz-Ares, L, Robles-Diaz, L, Wilkens, LR, Garcia, MJ, Intermaggio, MP, Alcaraz, M-L, Brett, MA, Beckmann, MW, Jimenez-Linan, M, Anglesio, M, Carney, ME, Schneider, M, Traficante, N, Pejovic, N, Singh, N, Le, N, Sinn, P, Ghatage, P, Erber, R, Edwards, R, Vierkant, R, Ness, RB, Leung, S, Orsulic, S, Brucker, SY, Kaufmann, SH, Fereday, S, Gayther, S, Winham, SJ, Kommoss, S, Pejovic, T, Longacre, TA, McGuire, V, Rhenius, V, Sieh, W, Shvetsov, YB, Whittemore, AS, Staebler, A, Karlan, BY, Rodriguez-Antona, C, Bowtell, DD, Goode, EL, Hogdall, E, Candido dos Reis, FJ, Gronwald, J, Chang-Claude, J, Moysich, KB, Kelemen, LE, Cook, LS, Goodman, MT, Fasching, PA, Crawford, R, Deen, S, Menon, U, Huntsman, DG, Kobel, M, Ramus, SJ, Pharoah, PDP, and Brenton, JD

Abstract

BACKGROUND: PTEN loss is a putative driver in histotypes of ovarian cancer (high-grade serous (HGSOC), endometrioid (ENOC), clear cell (CCOC), mucinous (MOC), low-grade serous (LGSOC)). We aimed to characterise PTEN expression as a biomarker in epithelial ovarian cancer in a large population-based study. METHODS: Tumours from 5400 patients from a multicentre observational, prospective cohort study of the Ovarian Tumour Tissue Analysis Consortium were used to evaluate associations between immunohistochemical PTEN patterns and overall survival time, age, stage, grade, residual tumour, CD8+ tumour-infiltrating lymphocytes (TIL) counts, expression of oestrogen receptor (ER), progesterone receptor (PR) and androgen receptor (AR) by means of Cox proportional hazard models and generalised Cochran-Mantel-Haenszel tests. RESULTS: Downregulation of cytoplasmic PTEN expression was most frequent in ENOC (most frequently in younger patients; p value = 0.0001) and CCOC and was associated with longer overall survival in HGSOC (hazard ratio: 0.78, 95% CI: 0.65-0.94, p value = 0.022). PTEN expression was associated with ER, PR and AR expression (p values: 0.0008, 0.062 and 0.0002, respectively) in HGSOC and with lower CD8 counts in CCOC (p value < 0.0001). Heterogeneous expression of PTEN was more prevalent in advanced HGSOC (p value = 0.019) and associated with higher CD8 counts (p value = 0.0016). CONCLUSIONS: PTEN loss is a frequent driver in ovarian carcinoma associating distinctly with expression of hormonal receptors and CD8+ TIL counts in HGSOC and CCOC histotypes.

Published
2020

43. 761P Impact of the combination of durvalumab (MEDI4736) plus olaparib (AZD2281) administered prior to surgery in the molecular profile of resectable urothelial bladder cancer. NEODURVARIB trial

Author

Rodriguez-Moreno, J.F., primary, de Velasco, G., additional, Alvarez-Fernandez, C., additional, Collado, R., additional, Fernandez-Rodriguez, R., additional, Estevez, S. Vazquez, additional, Virizuela Echaburu, J.A., additional, Gajate Borau, P., additional, Font, A., additional, Lainez, N., additional, Sevillano Fernandez, E., additional, Ruiz, S., additional, Beltran, L., additional, Rodriguez-Antona, C., additional, Berraondo, P., additional, and Garcia-Donas, J., additional

Published
2020
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44. 1069P A multicenter phase II study of nivolumab combined with ipilimumab in patients with pediatric solid tumours in adulthood (GETHI021)

Author

Rubio, X. Mielgo, primary, Diaz-Beveritge, R., additional, Sanchez, J.M. Sepulveda, additional, Pineda, E., additional, Salgado, M.Á. Vaz, additional, Lecumberri, M.J., additional, Valverde, C., additional, Castro, R. Lopez, additional, López, C., additional, Echaburu, J.A. Virizuela, additional, Salas, N. Rodriguez, additional, Bataller, R. de las Penas, additional, Lopez, R. Lopez, additional, Rodriguez, J. Medina, additional, Rodriguez-Antona, C., additional, Berraondo, P., additional, Rodriguez-Moreno, J.F., additional, Nuño, A. Hurtado, additional, Sevillano, E., additional, and Garcia-Donas, J., additional

Published
2020
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45. Surgery for prosthetic valve endocarditis: A retrospective study of a national registry

Author

Corte, A, Di Mauro, M, Dato, G, Barili, F, Cugola, D, Gelsomino, S, Sante, P, Carozza, A, Ratta, E, Galletti, L, Devotini, R, Casabona, R, Santini, F, Salsano, A, Scrofani, R, Antona, C, De Vincentiis, C, Biondi, A, Beghi, C, Cappabianca, G, De Bonis, M, Pozzoli, A, Nicolini, F, Benassi, F, Pacini, D, Di Bartolomeo, R, De Martino, A, Bortolotti, U, Lorusso, R, Vizzardi, E, Di Giammarco, G, Marinelli, D, Villa, E, Troise, G, Paparella, D, Margari, V, Tritto, F, Damiani, G, Scrascia, G, Zaccaria, S, Renzulli, A, Serraino, G, Mariscalco, G, Maselli, D, Parolari, A, Nappi, G, Corte A. D., Di Mauro M., Dato G. A., Barili F., Cugola D., Gelsomino S., Sante P., Carozza A., Ratta E. D., Galletti L., Devotini R., Casabona R., Santini F., Salsano A., Scrofani R., Antona C., De Vincentiis C., Biondi A., Beghi C., Cappabianca G., De Bonis M., Pozzoli A., Nicolini F., Benassi F., Pacini D., Di Bartolomeo R., De Martino A., Bortolotti U., Lorusso R., Vizzardi E., Di Giammarco G., Marinelli D., Villa E., Troise G., Paparella D., Margari V., Tritto F., Damiani G., Scrascia G., Zaccaria S., Renzulli A., Serraino G., Mariscalco G., Maselli D., Parolari A., Nappi G., Corte, A, Di Mauro, M, Dato, G, Barili, F, Cugola, D, Gelsomino, S, Sante, P, Carozza, A, Ratta, E, Galletti, L, Devotini, R, Casabona, R, Santini, F, Salsano, A, Scrofani, R, Antona, C, De Vincentiis, C, Biondi, A, Beghi, C, Cappabianca, G, De Bonis, M, Pozzoli, A, Nicolini, F, Benassi, F, Pacini, D, Di Bartolomeo, R, De Martino, A, Bortolotti, U, Lorusso, R, Vizzardi, E, Di Giammarco, G, Marinelli, D, Villa, E, Troise, G, Paparella, D, Margari, V, Tritto, F, Damiani, G, Scrascia, G, Zaccaria, S, Renzulli, A, Serraino, G, Mariscalco, G, Maselli, D, Parolari, A, Nappi, G, Corte A. D., Di Mauro M., Dato G. A., Barili F., Cugola D., Gelsomino S., Sante P., Carozza A., Ratta E. D., Galletti L., Devotini R., Casabona R., Santini F., Salsano A., Scrofani R., Antona C., De Vincentiis C., Biondi A., Beghi C., Cappabianca G., De Bonis M., Pozzoli A., Nicolini F., Benassi F., Pacini D., Di Bartolomeo R., De Martino A., Bortolotti U., Lorusso R., Vizzardi E., Di Giammarco G., Marinelli D., Villa E., Troise G., Paparella D., Margari V., Tritto F., Damiani G., Scrascia G., Zaccaria S., Renzulli A., Serraino G., Mariscalco G., Maselli D., Parolari A., and Nappi G.

Abstract

OBJECTIVES: We described clinical-epidemiological features of prosthetic valve endocarditis (PVE) and assessed the determinants of early surgical outcomes in multicentre design. METHODS: Data regarding 2823 patients undergoing surgery for endocarditis at 19 Italian Centers between 1979 and 2015 were collected in a database. Of them, 582 had PVE: in this group, the determinants of early mortality and complications were assessed, also taking into account the different chronological eras encompassed by the study. RESULTS: Overall hospital (30-day) mortality was 19.2% (112 patients). Postoperative complications of any type occurred in 256 patients (44%). Across 3 eras (1980-2000, 2001-08 and 2009-14), early mortality did not significantly change (20.4%, 17.1%, 20.5%, respectively, P = 0.60), whereas complication rate increased (18.5%, 38.2%, 52.8%, P < 0.001), consistent with increasing mean patient age (56 ± 14, 64 ± 15, 65 ± 14 years, respectively, P < 0.001) and median logistic EuroSCORE (14%, 21%, 23%, P = 0.025). Older age, female sex, preoperative serum creatinine > -2 mg/dl, chronic pulmonary disease, low ejection fraction, non-streptococcal aetiology, active endocarditis, preoperative intubation, preoperative shock and triple valve surgery were significantly associated with mortality. In multivariable analysis, age (OR = 1.02; P = 0.03), renal insufficiency (OR = 2.1; P = 0.05), triple valve surgery (OR = 6.9; P = 0.004) and shock (OR = 4.5; P < 0.001) were independently associated with mortality, while streptococcal aetiology, healed endocarditis and ejection fraction with survival. Adjusting for study era, preoperative shock (OR = 3; P < 0.001), Enterococcus (OR = 2.3; P = 0.01) and female sex (OR = 1.5; P = 0.03) independently predicted complications, whereas ejection fraction was protective. CONCLUSIONS: PVE surgery remains a high-risk one. The strongest predictors of early outcome of PVE surgery are related to patient's haemodynamic status an

Published
2017

46. A predictive model for early mortality after surgical treatment of heart valve or prosthesis infective endocarditis. The EndoSCORE

Author

Di Mauro, M, Dato, G, Barili, F, Gelsomino, S, Sante, P, Corte, A, Carrozza, A, Ratta, E, Cugola, D, Galletti, L, Devotini, R, Casabona, R, Santini, F, Salsano, A, Scrofani, R, Antona, C, Botta, L, Russo, C, Mancuso, S, Rinaldi, M, De Vincentiis, C, Biondi, A, Beghi, C, Cappabianca, G, Tarzia, V, Gerosa, G, De Bonis, M, Pozzoli, A, Nicolini, F, Benassi, F, Rosato, F, Grasso, E, Livi, U, Sandro, S, Pacini, D, Di Bartolomeo, R, De Martino, A, Bortolotti, U, Onorati, F, Faggian, G, Lorusso, R, Vizzardi, E, Di Giammarco, G, Marinelli, D, Villa, E, Troise, G, Piciche, M, Musumeci, F, Paparella, D, Margari, V, Tritto, F, Damiani, G, Scrascia, G, Zaccaria, S, Renzulli, A, Serraino, G, Mariscalco, G, Maselli, D, Foschi, M, Parolari, A, Nappi, G, Di Mauro M., Dato G. M. A., Barili F., Gelsomino S., Sante P., Corte A. D., Carrozza A., Ratta E. D., Cugola D., Galletti L., Devotini R., Casabona R., Santini F., Salsano A., Scrofani R., Antona C., Botta L., Russo C., Mancuso S., Rinaldi M., De Vincentiis C., Biondi A., Beghi C., Cappabianca G., Tarzia V., Gerosa G., De Bonis M., Pozzoli A., Nicolini F., Benassi F., Rosato F., Grasso E., Livi U., Sandro S., Pacini D., Di Bartolomeo R., De Martino A., Bortolotti U., Onorati F., Faggian G., Lorusso R., Vizzardi E., Di Giammarco G., Marinelli D., Villa E., Troise G., Piciche M., Musumeci F., Paparella D., Margari V., Tritto F., Damiani G., Scrascia G., Zaccaria S., Renzulli A., Serraino G., Mariscalco G., Maselli D., Foschi M., Parolari A., Nappi G., Di Mauro, M, Dato, G, Barili, F, Gelsomino, S, Sante, P, Corte, A, Carrozza, A, Ratta, E, Cugola, D, Galletti, L, Devotini, R, Casabona, R, Santini, F, Salsano, A, Scrofani, R, Antona, C, Botta, L, Russo, C, Mancuso, S, Rinaldi, M, De Vincentiis, C, Biondi, A, Beghi, C, Cappabianca, G, Tarzia, V, Gerosa, G, De Bonis, M, Pozzoli, A, Nicolini, F, Benassi, F, Rosato, F, Grasso, E, Livi, U, Sandro, S, Pacini, D, Di Bartolomeo, R, De Martino, A, Bortolotti, U, Onorati, F, Faggian, G, Lorusso, R, Vizzardi, E, Di Giammarco, G, Marinelli, D, Villa, E, Troise, G, Piciche, M, Musumeci, F, Paparella, D, Margari, V, Tritto, F, Damiani, G, Scrascia, G, Zaccaria, S, Renzulli, A, Serraino, G, Mariscalco, G, Maselli, D, Foschi, M, Parolari, A, Nappi, G, Di Mauro M., Dato G. M. A., Barili F., Gelsomino S., Sante P., Corte A. D., Carrozza A., Ratta E. D., Cugola D., Galletti L., Devotini R., Casabona R., Santini F., Salsano A., Scrofani R., Antona C., Botta L., Russo C., Mancuso S., Rinaldi M., De Vincentiis C., Biondi A., Beghi C., Cappabianca G., Tarzia V., Gerosa G., De Bonis M., Pozzoli A., Nicolini F., Benassi F., Rosato F., Grasso E., Livi U., Sandro S., Pacini D., Di Bartolomeo R., De Martino A., Bortolotti U., Onorati F., Faggian G., Lorusso R., Vizzardi E., Di Giammarco G., Marinelli D., Villa E., Troise G., Piciche M., Musumeci F., Paparella D., Margari V., Tritto F., Damiani G., Scrascia G., Zaccaria S., Renzulli A., Serraino G., Mariscalco G., Maselli D., Foschi M., Parolari A., and Nappi G.

Abstract

Background The aim of this large retrospective study was to provide a logistic risk model along an additive score to predict early mortality after surgical treatment of patients with heart valve or prosthesis infective endocarditis (IE). Methods From 2000 to 2015, 2715 patients with native valve endocarditis (NVE) or prosthesis valve endocarditis (PVE) were operated on in 26 Italian Cardiac Surgery Centers. The relationship between early mortality and covariates was evaluated with logistic mixed effect models. Fixed effects are parameters associated with the entire population or with certain repeatable levels of experimental factors, while random effects are associated with individual experimental units (centers). Results Early mortality was 11.0% (298/2715); At mixed effect logistic regression the following variables were found associated with early mortality: age class, female gender, LVEF, preoperative shock, COPD, creatinine value above 2 mg/dl, presence of abscess, number of treated valve/prosthesis (with respect to one treated valve/prosthesis) and the isolation of Staphylococcus aureus, Fungus spp., Pseudomonas Aeruginosa and other micro-organisms, while Streptococcus spp., Enterococcus spp. and other Staphylococci did not affect early mortality, as well as no micro-organisms isolation. LVEF was found linearly associated with outcomes while non-linear association between mortality and age was tested and the best model was found with a categorization into four classes (AUC = 0.851). Conclusions The following study provides a logistic risk model to predict early mortality in patients with heart valve or prosthesis infective endocarditis undergoing surgical treatment, called “The EndoSCORE”.

Published
2017

50. Integrative multi-omics analysis identifies a prognostic miRNA signature and a targetable miR-21-3p/TSC2/mTOR axis in metastatic pheochromocytoma/paraganglioma

Author

Calsina, B., Castro-Vega, L.J., Torres-Perez, R., Inglada-Perez, L., Curras-Freixes, M., Roldan-Romero, J.M., Mancikova, V., Leton, R., Remacha, L., Santos, M., Burnichon, N., Lussey-Lepoutre, C., Rapizzi, E., Grana, O., Alvarez-Escola, C., Cubas, A.A. de, Lanillos, J., Cordero-Barreal, A., Martinez-Montes, A.M., Bellucci, A., Amar, L., Fernandes-Rosa, F.L., Calatayud, M., Aller, J., Lamas, C., Sastre-Marcos, J., Canu, L., Korpershoek, E., Timmers, H.J.L.M., Lenders, J.W.M., Beuschlein, F., Fassnacht-Capeller, M., Eisenhofer, G., Mannelli, M., Al-Shahrour, F., Favier, J., Rodriguez-Antona, C., Cascon, A., Montero-Conde, C., Gimenez-Roqueplo, A.P., Robledo, M., Calsina, B., Castro-Vega, L.J., Torres-Perez, R., Inglada-Perez, L., Curras-Freixes, M., Roldan-Romero, J.M., Mancikova, V., Leton, R., Remacha, L., Santos, M., Burnichon, N., Lussey-Lepoutre, C., Rapizzi, E., Grana, O., Alvarez-Escola, C., Cubas, A.A. de, Lanillos, J., Cordero-Barreal, A., Martinez-Montes, A.M., Bellucci, A., Amar, L., Fernandes-Rosa, F.L., Calatayud, M., Aller, J., Lamas, C., Sastre-Marcos, J., Canu, L., Korpershoek, E., Timmers, H.J.L.M., Lenders, J.W.M., Beuschlein, F., Fassnacht-Capeller, M., Eisenhofer, G., Mannelli, M., Al-Shahrour, F., Favier, J., Rodriguez-Antona, C., Cascon, A., Montero-Conde, C., Gimenez-Roqueplo, A.P., and Robledo, M.

Abstract

Contains fulltext : 208812.pdf (publisher's version ) (Open Access), Rationale: Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors that present variable outcomes. To date, no effective therapies or reliable prognostic markers are available for patients who develop metastatic PPGL (mPPGL). Our aim was to discover robust prognostic markers validated through in vitro models, and define specific therapeutic options according to tumor genomic features. Methods: We analyzed three PPGL miRNome datasets (n=443), validated candidate markers and assessed them in serum samples (n=36) to find a metastatic miRNA signature. An integrative study of miRNome, transcriptome and proteome was performed to find miRNA targets, which were further characterized in vitro. Results: A signature of six miRNAs (miR-21-3p, miR-183-5p, miR-182-5p, miR-96-5p, miR-551b-3p, and miR-202-5p) was associated with metastatic risk and time to progression. A higher expression of five of these miRNAs was also detected in PPGL patients' liquid biopsies compared with controls. The combined expression of miR-21-3p/miR-183-5p showed the best power to predict metastasis (AUC=0.804, P=4.67.10(-18)), and was found associated in vitro with pro-metastatic features, such as neuroendocrine-mesenchymal transition phenotype, and increased cell migration rate. A pan-cancer multi-omic integrative study correlated miR-21-3p levels with TSC2 expression, mTOR pathway activation, and a predictive signature for mTOR inhibitor-sensitivity in PPGLs and other cancers. Likewise, we demonstrated in vitro a TSC2 repression and an enhanced rapamycin sensitivity upon miR-21-3p expression. Conclusions: Our findings support the assessment of miR-21-3p/miR-183-5p, in tumors and liquid biopsies, as biomarkers for risk stratification to improve the PPGL patients' management. We propose miR-21-3p to select mPPGL patients who may benefit from mTOR inhibitors.

Published
2019

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