27 results on '"Kolansky D"'
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2. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy
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Perkovic, V., Jardine, M. J., Neal, B., Bompoint, S., Heerspink, H. J. L., Charytan, D. M., Edwards, R., Agarwal, R., Bakris, G., Bull, S., Cannon, C. P., Capuano, G., Chu, P. -L., De Zeeuw, D., Greene, T., Levin, A., Pollock, C., Wheeler, D. C., Yavin, Y., Zhang, H., Zinman, B., Meininger, G., Brenner, B. M., Mahaffey, K. W., Perkovic, V, Mahaffey, Kw, Agarwal, R, Bakris, G, Brenner, Bm, Cannon, Cp, Charytan, Dm, de Zeeuw, D, Greene, T, Jardine, Mj, Heerspink, Hjl, Levin, A, Meininger, G, Neal, B, Pollock, C, Wheeler, Dc, Zhang, H, Zinman, B, Mcguire, Dk, Holman, R, Home, P, Scharfstein, D, Parfrey, P, Shahinfar, S, August, P, Chang, T, Sinha, Ad, Januzzi, J, Kolansky, D, Amerena, J, Hillis, G, Gorelick, P, Kissela, B, Kasner, S, Lindley, R, Fulcher, G, Ounadjela, S, Hufert, K, von Ingersleben, G, Gaglia, J, Harris, R, Hudson, M, Turchin, A, Cheifetz, A, Sheth, S, Feuerstein, J, Cohen, S, Jardine, M, Li, N, Kolesnyk, I, Aizenberg, D, Pecoits-Filho, R, Cherney, D 3rd, Obrador, G, Chertow, G, Hawley, C, Ji, L, Wada, T, Jha, V, Lim, Sk, Lim-Abrahan, Ma, Santos, F, Chae, Dw, Hwang, Sj, Vazelov, E, Rychlík, I, Hadjadj, S, Krane, V, Rosivall, L, De Nicola, L, Dreval, A, Nowicki, M, Schiller, A, Distiller, L, Górriz, Jl, Kolesnyk, M, Morren, F, Goykhman, S, David, C, Yost, L, Wang, H, Hettiarachchi, M, Thimmaiah, R, Koppolu, D, George, S, Schmidt, M, Ignjatovic, J, Chapin, L, Travis, K, Destree, M, Sood, V, Coffee, L, De Brouwer, K, Zaviriukha, V, Starzec, A, Koizumi, M, Lin, G, Chen, E, Lin, P, Leia, C, Mascaro, D, Amigo, A, Limos, A, Abrahamsen, I, Jaffer, S, Ahuad Guerrero RA, Albisu, Jp, Alvarisqueta, A, Bartolacci, I, Berli, Ma, Bordonava, A, Calella, P, Cantero, Mc, Cartasegna, Lr, Cercos, E, Coloma, Gc, Colombo, H, Commendatore, V, Cuadrado, J, Cuneo, Ca, Cusumano, Am, Douthat, Wg, Dran, Rd, Farias, E, Fernandez, Mf, Finkelstein, H, Fragale, G, Fretes, Jo, Garcia, Nh, Gastaldi, A, Gelersztein, E, Glenny, Ja, Gonzalez, Jp, Gonzalez Colaso PDC, Goycoa, C, Greloni, Gc, Guinsburg, A, Hermida, S, Juncos, Li, Klyver, Mi, Kraft, F, Krynski, F, Lanchiotti, Pv, Leon de la Fuente RA, Marchetta, N, Mele, P, Nicolai, S, Novoa, Pa, Orio, Si, Otreras, F, Oviedo, A, Raffaele, P, Resk, Jh, Rista, L, Rodriguez Papini, N, Sala, J, Santos, Jc, Schiavi, Lb, Sessa, H, Smith Casabella, T, Ulla, Mr, Valdez, M, Vallejos, A, Villarino, A, Visco, Ve, Wassermann, A, Zaidman, Cj, Cheung, Nw, Droste, C, Fraser, I, Johnson, D, Mah, Pm, Nicholls, K, Packham, D, Proietto, J, Roberts, A, Roger, S, Tsang, V, Raduan, Ra, Alves da Costa FA, Amodeo, C, Andreotti Turatti LA, Bregman, R, Camelo Sanches FC, Canani, Lh, Chacra, Ar, Cunha Borges JL, Cunha Vêncio SA, da Silva Franco RJ, D'Avila, D, de Souza Portes, E, de Souza, P, Deboni, Lm, Filho, Ff, Geloneze Neto, B, Gomes, M, Kohara, Sk, Keitel, E, Kerr Saraiva JF, Kurtz Lisboa HR, de Carvalho Contieri FL, Milagres, R, Montenegro Junior, R, Moreira de Brito, C, Nazzer Hissa, M, Nazario Sabbag ÂR, Noronha, I, Panarotto, D, Pecoits Filho, R, Pereira, Ma, Saporito, W, Scotton, As, Schuch, T, Simões de Almeida, R, Slompo Ramos, C, Soares Felício, J, Thomé, F, Tibes Hachmann JC, Yamada, S, Yoiti Hayashida, C, Zanata Petry TB, Zanella, Mt, Andreeva, V, Angelova, A, Dimitrov, S, Genadieva, V, Genova-Hristova, G, Hristozov, K, Kamenov, Z, Koundurdjiev, A, Lozanov, L, Margaritov, V, Nonchev, B, Rangelov, R, Shinkov, A, Temelkova, M, Velichkova, E, Yakov, A, Aggarwal, N, Aronson, R, Bajaj, H, Chouinard, G, Conway, J, Cournoyer, S, Daroza, G, De Serres, S, Dubé, F, Goldenberg, R, Gupta, A, Gupta, M, Henein, S, Khandwala, H, Leiter, L, Madore, F, Mcmahon, A, Muirhead, N, Pichette, V, Rabasa-Lhoret, R, Steele, A, Tangri, N, Torshizi, A, Woo, V, Zalunardo, N, Fernández Montenegro MA, Godoy Jorquera JG, Medina Fariña, M, Saavedra Gajardo, V, Vejar, M, Chen, N, Chen, Q, Gan, S, Kong, Y, Li, D, Li, W, Li, X, Lin, H, Liu, J, Lu, W, Mao, H, Ren, Y, Song, W, Sun, J, Sun, L, Tu, P, Wang, G, Yang, J, Yin, A, Yu, X, Zhao, M, Zheng, H, Accini Mendoza JL, Arcos, E, Avendano, J, Diaz Ruiz JEA, Garcia Ortiz LH, Gonzalez, A, Hernandez Triana, E, Higuera, Jd, Malaver, N, Molina de Salazar DI, Rosero, R, Terront Lozano MA, Valderrama Cometa, L, Valenzuela, A, Vargas Alonso RD, Villegas, I, Yupanqui, H, Bartaskova, D, Barton, P, Belobradkova, J, Dohnalova, L, Drasnar, T, Ferkl, R, Halciakova, K, Klokocnikova, V, Kovar, R, Lastuvka, J, Lukac, M, Pesickova, S, Peterka, K, Pumprla, J, Rychlik, I, Saudek, F, Tesar, V, Valis, M, Weiner, P, Zemek, S, Alamartine, E, Borot, S, Cariou, B, Dussol, B, Fauvel, Jp, Gourdy, P, Klein, A, Le Meur, Y, Penfornis, A, Roussel, R, Saulnier, Pj, Thervet, E, Zaoui, P, Burst, V, Faghih, M, Faulmann, G, Haller, H, Jerwan-Keim, R, Maxeiner, S, Paschen, B, Plassmann, G, Rose, L, Gonzalez Orellana RA, Haase, Fp, Moreira Diaz JP, Ramirez Roca LA, Sánchez Arenales JA, Sanchez Polo JV, Turcios Juarez, E, Csecsei, G, Csiky, B, Danos, P, Deak, L, Dudas, M, Harcsa, E, Keltai, K, Keresztesi, S, Kiss, K, Konyves, L, Major, L, Mileder, M, Molnar, M, Mucsi, J, Oroszlan, T, Ory, I, Paragh, G, Peterfai, E, Petro, G, Revesz, K, Takacs, R, Vangel, S, Vasas, S, Zsom, M, Abraham, O, Bhushan, Rs, Deepak, D, Edwin, Fm, Gopalakrishnan, N, Gracious, N, Hansraj, A, Jain, D, Keshavamurthy, Cb, Khullar, D, Manisha, S, Peringat, J, Prasad, N, Satyanarayana, Rk, Sreedhar, R, Sreelatha, M, Sudhakar, B, Vyasam, Rc, Bonadonna, R, Castellino, P, Ceriello, A, Chiovato, L, De Cosmo, S, Derosa, G, Di Carlo, A, Di Cianni, G, Frascà, G, Fuiano, G, Gambaro, G, Garibotto, G, Giorda, C, Malberti, F, Mandreoli, M, Mannucci, E, Orsi, E, Piatti, P, Santoro, D, Sasso, Fc, Serviddio, G, Stella, A, Trevisan, R, Veronelli, Am, Zanoli, L, Akiyama, H, Aoki, H, Asano, A, Iitsuka, T, Kajiyama, S, Kashine, S, Kawada, T, Kodera, T, Kono, H, Koyama, K, Kumeda, Y, Miyauchi, S, Mizuyama, K, Niiya, T, Oishi, H, Ota, S, Sakakibara, T, Takai, M, Tomonaga, O, Tsujimoto, M, Wakasugi, M, Wakida, Y, Watanabe, T, Yamada, M, Yanagida, K, Yanase, T, Yumita, W, Gaupsiene, E, Kozloviene, D, Navickas, A, Urbanaviciene, E, Abdul Ghani, R, Abdul Kadir, K, Ali, N, Che Yusof MD, Gan, Cl, Ismail, M, Kong, Wy, Lam, Sw, Lee, Ly, Loh, Cl, Manocha, Ab, Ng, Ks, Nik Ahmad NNF, Ratnasingam, V, Bin Shudim SS, Vengadasalam, P, Abraira Munoz LD, Salazar, Ma, Cruz, Jb, Soto, Mb, Ramos, Jc, Wong, Ac, Correa Rotter JR, Diaz Escalante, T, Enriquez Sosa FE, Flores Lozano, F, Flota Cervera LF, Frenk Baron, P, Garcia Ballesteros, C, Gomez Rangel JD, Herrera Jimenez LE, Irizar Santana SS, Jimenez Florez, F, Laviada Molina, H, Luna Ceballos RI, Martin Del Camp Blanco, B, Morales Franco, G, Moreno Loza OT, Mustieles Rocha, C, Obrador Vera, G, Orozco Castellanos, R, Peralta Calcaneo, J, Reyes Rosano MA, Rodriguez Pattzi, H, Rosas Guzman, J, Rucker Joerg IE, Saaveddra Sanchez SB, Sanchez Mijangos JH, Serrano Sanson, P, Tamayo, Y Orozco JA, Tellez Chavez, E, Valdes Depeda, A, Venegas Carrillo, L, Villagordoa Mesa, J, Zamarripa Escobedo, R, Baker, J, Noonan, P, Scott, R, Walker, R, Watson, E, Williams, M, Young, S, Abejuela, Z, Agra, J, Aquitania, G, Caringal, C, Comia, Rs, Delos Santos, L, Gomez, O, Jimeno, C, Tan, G, Tolentino, M, Yao, C, Yap, Ye, Ygpuara, Mdl, Bijata-Bronisz, R, Hotlos, L, Januszewicz, A, Kaczmarek, B, Kaminska, A, Lazuka, L, Madej, A, Mazur, S, Mlodawska-Choluj, D, Orlowska-Kowalik, G, Popenda, G, Rewerska, B, Sowinski, D, Angelescu, Lm, Anghel, V, Avram, Ri, Busegeanu, Mm, Cif, A, Cosma, D, Crisan, C, Demian, Ld, Ferariu, Ie, Halmagyi, I, Hancu, N, Munteanu, M, Negru, D, Onaca, Ag, Petrica, L, Popa, Ar, Ranetti, Ae, Serafinceanu, C, Toarba, C, Agafyina, A, Barbarash, O, Barysheva, O, Chizhov, D, Dobronravov, V, Glinkina, I, Grineva, E, Khirmanov, V, Kolmakova, E, Koroleva, T, Kvitkova, L, Marasaev, V, Mkrtumyan, A, Morugova, T, Nagibovich, G, Nagibovich, O, Nedogoda, S, Osipova, I, Raskina, T, Samoylova, Y, Sazonova, O, Shamkhalova, M, Shutemova, E, Shwartz, Y, Uriasyev, O, Vorobyev, S, Zateyshchikova, A, Zateyshshikov, D, Zykova, T, Antic, S, Djordjevic, M, Kendereski, A, Lalic, K, Lalic, N, Popovic-Radinovic, V, Babikova, J, Benusova, O, Buganova, I, Culak, J, Dzupina, A, Dzuponova, J, Fulop, P, Ilavska, A, Martinka, E, Ochodnicka, Z, Pella, D, Smatanova, I, Ahmed, F, Badat, A, Breedt, J, Govender, V, Govender, R, Joshi, M, Jurgens, J, Latiff, G, Lombard, L, Mookadam, M, Ngcakani, N, Nortje, H, Oosthuizen, H, Pillay-Ramaya, L, Prozesky, H, Reddy, J, Rheeder, P, Seeber, M, Cho, Ym, Jeong, Ik, Kim, Sg, Kim, Yh, Kwon, Hs, Kwon, Mj, Lee, Bw, Lee, J, Lee, Mk, Nam, Ms, Oh, Kh, Park, Cy, Park, Sh, Yoon, Kh, Alvarez Garcia, P, Asmarats Mercadal, L, Barrios, C, Cereto Castro, F, Cigarran Guldris, S, Dominquez Lopez, M, Egido de Los Rios, J, Fernandez Fresnedo, G, Galan Serrano, A, Garcia, I, Gonzalez Martinez FJ, Jodar Gimeno JE, Muñoz Lopez Mendoza, M, Malek Marin, T, Morales Portillo, C, Munar Vila MA, Muñoz Torres, M, Nieto Iglesias, J, Pantoja Perez, J, Perez Vera, M, Portoles Perez JM, Quesada Simón MA, Simo Canonge, R, Soto Gonzalez, A, Terns Riera, M, Tinahones Madueno FJ, Plaza, Mv, Chang, Ct, Chuang, Lm, Hsia, Tl, Hsieh, Ch, Lin, Cc, Lu, Yc, Sheu, Wh, Barna, O, Bilyk, Sd, Botsyurko, V, Dudar, I, Fushtey, I, Godlevska, O, Golovchenko, O, Gyrina, O, Kazmirchuk, A, Komisarenko, I, Korzh, O, Kravchun, N, Legun, O, Mankovskyy, B, Martynyuk, L, Mostovoy, Y, Pashkovska, N, Pererva, L, Pertseva, T, Samoylov, O, Smirnov, I, Svyshchenko, Y, Tomashkevych, H, Topchii, I, Tryshchuk, N, Tseluyko, V, Vizir, V, Vlasenko, M, Zlova, T, Zub, L, Abusnana, S, Railey, M, Abouglila, K, Ainsworth, P, Ali, Z, Arutchelvam, V, Barnard, M, Bellary, S, Davies, E, Davies, M, Davies, S, Dawson, A, El Kossi, M, English, P, Fraser, D, Gnudi, L, Gunstone, A, Hall, T, Hanif, W, Jackson, A, Johnson, A, Joseph, F, Krishnan, S, Kumwenda, M, Macdougall, I, Nixon, P, O'Hare, J, Philip, S, Ramtoola, S, Saxena, M, Sennik, D, Simon, G, Singh, B, Stephens, J, Strzelecka, A, Symonds, R, Turner, W, Wahba, M, Wakeling, J, Wheeler, D, Winocour, P, Abdallah, J, Abdullah, R, Abramowitz, M, Acosta, I, Aiello, J, Akright, L, Akyea-Djamson, A, Alappan, R, Alicic, R, Al-Karadsheh, A, Allison, Dc, Arauz-Pacheco, C, Arfeen, S, Arif, A, Arvind, M, Atray, N, Awad, A, Barnhill, P, Barranco, E, Barrera, C, Beacom, M, Behara, V, Belo, D, Bentley-Lewis, R, Berenguer, R, Bermudez, L, Bernardo, M, Biscoveanu, M, Bowman-Stroud, C, Brandon, D, Brusco, O, Busch, R, Canaan, Y, Chilito, A, Christensen, T, Christiano, C, Christofides, E, Chuateco, C, Cohen, K, Cohen, R, Cohen-Stein, D, Cook, C, Coyne, D, Daboul, N, Darwish, R, Daswani, A, Deck, K, Desouza, C, Dev, D, Dhillon, M, Dua, S, Eder, F, Elosegui, Am, El-Shahawy, M, Ervin, J, Esquenazi, A, Evans, J, Fishbane, S, Frias, J, Galindo-Ramos, E, Galphin, C, Ghazi, A, Gonzalez, E, Gorson, D, Gowda, A, Greco, B, Grubb, S, Gulati, R, Hammoud, J, Handelsman, S, Hartman, I, Hershon, K, Hiser, D, Hon, G, Jacob, R, Jaime, M, Jamal, A, Kaupke, C, Keightley, G, Kern, E, Khanna, R, Khitan, Z, Kim, S, Kopyt, N, Kovesdy, C, Krishna, G, Kropp, J, Kumar, A, Kumar, J, Kumar, N, Kusnir, J, Lane, W, Lawrence, M, Lehrner, L, Lentz, J, Levinson, D, Lewis, D, Liss, K, Maddux, A, Maheshwari, H, Mandayam, S, Marar, I, Mehta, B, Middleton, J, Mordujovich, J, Moreda, R, Moustafa, M, Mujica Trenche, S, Narayanan, M, Narvarte, J, Nassar, T, Newman, G, Nichol, B, Nicol, P, Nisnisan, J, Nossuli, Ak, Obialo, C, Olelewe, S, Oliver, M, O'Shaughnessy, A, Padron, J, Pankhaniya, R, Parker, R, Patel, D, Patel, G, Patel, N, Pavon, H, Perez, A, Perez, C, Perlman, A, Pettis, K, Pharr, W, Phillips, A, Purighalla, R, Quesada-Suarez, L, Ranjan, R, Rastogi, S, Rendell, M, Rich, L, Robinson, M, Rodriguez, H, Rosas, S, Saba, F, Sankaram, R, Sarin, R, Schreiman, R, Scott, D, Sekkarie, M, Sensenbrenner, J, Shakeel, M, Shanik, M, Shaw, S, Smith, S, Solomon, R, Sprague, A, Spry, L, Suchinda, P, Sultan, S, Surampudi, P, Sussman, S, Tan, A, Terrelonge, A, Thompson, M, Trespalacios, F, Trippe, B, Trueba, P, Twahirwa, M, Updegrove, J, Van Buren, P, Vannorsdall, M, Varghese, F, Velasquez-Mieyer, P, Ventrapragada, S, Vukotic, G, Wadud, K, Warren, M, Watson, H, Watts, R, Weiner, D, Welker, J, Welsh, J, Williams, S, Zaniewski-Singh, M., Perkovic, Vlado, Jardine, Meg J, Neal, Bruce, Bompoint, Severine, Heerspink, Hiddo J L, Charytan, David M, Edwards, Robert, Agarwal, Rajiv, Bakris, George, Bull, Scott, Cannon, Christopher P, Capuano, George, Chu, Pei-Ling, de Zeeuw, Dick, Greene, Tom, Levin, Adeera, Pollock, Carol, Wheeler, David C, Yavin, Yshai, Zhang, Hong, Zinman, Bernard, Meininger, Gary, Brenner, Barry M, Mahaffey, Kenneth W, collaborator: Perkovic, V, Mahaffey, Kw, Agarwal, R, Bakris, G, Brenner, Bm, Cannon, Cp, Charytan, Dm, de Zeeuw, D, Greene, T, Jardine, Mj, Heerspink, Hjl, Levin, A, Meininger, G, Neal, B, Pollock, C, Wheeler, Dc, Zhang, H, Zinman, B, Mcguire, Dk, Holman, R, Home, P, Scharfstein, D, Parfrey, P, Shahinfar, S, August, P, Chang, T, Sinha, Ad, Januzzi, J, Kolansky, D, Amerena, J, Hillis, G, Gorelick, P, Kissela, B, Kasner, S, Lindley, R, Fulcher, G, Ounadjela, S, Hufert, K, von Ingersleben, G, Gaglia, J, Harris, R, Hudson, M, Turchin, A, Cheifetz, A, Sheth, S, Feuerstein, J, Cohen, S, Jardine, M, Li, N, Kolesnyk, I, Aizenberg, D, Pecoits-Filho, R, Cherney, D 3rd, Obrador, G, Chertow, G, Hawley, C, Ji, L, Wada, T, Jha, V, Lim, Sk, Lim-Abrahan, Ma, Santos, F, Chae, Dw, Hwang, Sj, Vazelov, E, Rychlík, I, Hadjadj, S, Krane, V, Rosivall, L, De Nicola, L, Dreval, A, Nowicki, M, Schiller, A, Distiller, L, Górriz, Jl, Kolesnyk, M, Morren, F, Goykhman, S, David, C, Yost, L, Wang, H, Hettiarachchi, M, Thimmaiah, R, Koppolu, D, George, S, Schmidt, M, Ignjatovic, J, Chapin, L, Travis, K, Destree, M, Sood, V, Coffee, L, De Brouwer, K, Zaviriukha, V, Starzec, A, Koizumi, M, Lin, G, Chen, E, Lin, P, Leia, C, Mascaro, D, Amigo, A, Limos, A, Abrahamsen, I, Jaffer, S, Ahuad Guerrero, Ra, Albisu, Jp, Alvarisqueta, A, Bartolacci, I, Berli, Ma, Bordonava, A, Calella, P, Cantero, Mc, Cartasegna, Lr, Cercos, E, Coloma, Gc, Colombo, H, Commendatore, V, Cuadrado, J, Cuneo, Ca, Cusumano, Am, Douthat, Wg, Dran, Rd, Farias, E, Fernandez, Mf, Finkelstein, H, Fragale, G, Fretes, Jo, Garcia, Nh, Gastaldi, A, Gelersztein, E, Glenny, Ja, Gonzalez, Jp, Gonzalez Colaso, Pdc, Goycoa, C, Greloni, Gc, Guinsburg, A, Hermida, S, Juncos, Li, Klyver, Mi, Kraft, F, Krynski, F, Lanchiotti, Pv, Leon de la Fuente, Ra, Marchetta, N, Mele, P, Nicolai, S, Novoa, Pa, Orio, Si, Otreras, F, Oviedo, A, Raffaele, P, Resk, Jh, Rista, L, Rodriguez Papini, N, Sala, J, Santos, Jc, Schiavi, Lb, Sessa, H, Smith Casabella, T, Ulla, Mr, Valdez, M, Vallejos, A, Villarino, A, Visco, Ve, Wassermann, A, Zaidman, Cj, Cheung, Nw, Droste, C, Fraser, I, Johnson, D, Mah, Pm, Nicholls, K, Packham, D, Proietto, J, Roberts, A, Roger, S, Tsang, V, Raduan, Ra, Alves da Costa, Fa, Amodeo, C, Andreotti Turatti, La, Bregman, R, Camelo Sanches, Fc, Canani, Lh, Chacra, Ar, Cunha Borges, Jl, Cunha Vêncio, Sa, da Silva Franco, Rj, D'Avila, D, de Souza Portes, E, de Souza, P, Deboni, Lm, Filho, Ff, Geloneze Neto, B, Gomes, M, Kohara, Sk, Keitel, E, Kerr Saraiva, Jf, Kurtz Lisboa, Hr, de Carvalho Contieri, Fl, Milagres, R, Montenegro Junior, R, Moreira de Brito, C, Nazzer Hissa, M, Nazario Sabbag, Âr, Noronha, I, Panarotto, D, Pecoits Filho, R, Pereira, Ma, Saporito, W, Scotton, A, Schuch, T, Simões de Almeida, R, Slompo Ramos, C, Soares Felício, J, Thomé, F, Tibes Hachmann, Jc, Yamada, S, Yoiti Hayashida, C, Zanata Petry, Tb, Zanella, Mt, Andreeva, V, Angelova, A, Dimitrov, S, Genadieva, V, Genova-Hristova, G, Hristozov, K, Kamenov, Z, Koundurdjiev, A, Lozanov, L, Margaritov, V, Nonchev, B, Rangelov, R, Shinkov, A, Temelkova, M, Velichkova, E, Yakov, A, Aggarwal, N, Aronson, R, Bajaj, H, Chouinard, G, Conway, J, Cournoyer, S, Daroza, G, De Serres, S, Dubé, F, Goldenberg, R, Gupta, A, Gupta, M, Henein, S, Khandwala, H, Leiter, L, Madore, F, Mcmahon, A, Muirhead, N, Pichette, V, Rabasa-Lhoret, R, Steele, A, Tangri, N, Torshizi, A, Woo, V, Zalunardo, N, Fernández Montenegro, Ma, Godoy Jorquera, Jg, Medina Fariña, M, Saavedra Gajardo, V, Vejar, M, Chen, N, Chen, Q, Gan, S, Kong, Y, Li, D, Li, W, Li, X, Lin, H, Liu, J, Lu, W, Mao, H, Ren, Y, Song, W, Sun, J, Sun, L, Tu, P, Wang, G, Yang, J, Yin, A, Yu, X, Zhao, M, Zheng, H, Accini Mendoza, Jl, Arcos, E, Avendano, J, Diaz Ruiz, Jea, Garcia Ortiz, Lh, Gonzalez, A, Hernandez Triana, E, Higuera, Jd, Malaver, N, Molina de Salazar, Di, Rosero, R, Terront Lozano, Ma, Valderrama Cometa, L, Valenzuela, A, Vargas Alonso, Rd, Villegas, I, Yupanqui, H, Bartaskova, D, Barton, P, Belobradkova, J, Dohnalova, L, Drasnar, T, Ferkl, R, Halciakova, K, Klokocnikova, V, Kovar, R, Lastuvka, J, Lukac, M, Pesickova, S, Peterka, K, Pumprla, J, Rychlik, I, Saudek, F, Tesar, V, Valis, M, Weiner, P, Zemek, S, Alamartine, E, Borot, S, Cariou, B, Dussol, B, Fauvel, Jp, Gourdy, P, Klein, A, Le Meur, Y, Penfornis, A, Roussel, R, Saulnier, Pj, Thervet, E, Zaoui, P, Burst, V, Faghih, M, Faulmann, G, Haller, H, Jerwan-Keim, R, Maxeiner, S, Paschen, B, Plassmann, G, Rose, L, Gonzalez Orellana, Ra, Haase, Fp, Moreira Diaz, Jp, Ramirez Roca, La, Sánchez Arenales, Ja, Sanchez Polo, Jv, Turcios Juarez, E, Csecsei, G, Csiky, B, Danos, P, Deak, L, Dudas, M, Harcsa, E, Keltai, K, Keresztesi, S, Kiss, K, Konyves, L, Major, L, Mileder, M, Molnar, M, Mucsi, J, Oroszlan, T, Ory, I, Paragh, G, Peterfai, E, Petro, G, Revesz, K, Takacs, R, Vangel, S, Vasas, S, Zsom, M, Abraham, O, Bhushan, R, Deepak, D, Edwin, Fm, Gopalakrishnan, N, Gracious, N, Hansraj, A, Jain, D, Keshavamurthy, Cb, Khullar, D, Manisha, S, Peringat, J, Prasad, N, Satyanarayana, Rk, Sreedhar, R, Sreelatha, M, Sudhakar, B, Vyasam, Rc, Bonadonna, R, Castellino, P, Ceriello, A, Chiovato, L, De Cosmo, S, Derosa, G, Di Carlo, A, Di Cianni, G, Frascà, G, Fuiano, G, Gambaro, G, Garibotto, G, Giorda, C, Malberti, F, Mandreoli, M, Mannucci, E, Orsi, E, Piatti, P, Santoro, D, Sasso, Fc, Serviddio, G, Stella, A, Trevisan, R, Veronelli, Am, Zanoli, L, Akiyama, H, Aoki, H, Asano, A, Iitsuka, T et al, Groningen Kidney Center (GKC), and Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET)
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Aged ,Canagliflozin ,Cardiovascular Diseases ,Creatinine ,Diabetes Mellitus, Type 2 ,Diabetic Nephropathies ,Double-Blind Method ,Female ,Follow-Up Studies ,Glomerular Filtration Rate ,Humans ,Kidney Failure, Chronic ,Male ,Middle Aged ,Sodium-Glucose Transporter 2 Inhibitors ,Type 2 diabetes ,030204 cardiovascular system & hematology ,Diabetic nephropathy ,Kidney Failure ,chemistry.chemical_compound ,0302 clinical medicine ,030212 general & internal medicine ,03.02. Klinikai orvostan ,Dapagliflozin ,Chronic ,11 Medical and Health Sciences ,EMPAGLIFLOZIN ,General Medicine ,Life Sciences & Biomedicine ,Type 2 ,medicine.drug ,medicine.medical_specialty ,Nephropathy ,03 medical and health sciences ,Medicine, General & Internal ,Internal medicine ,Diabetes mellitus ,General & Internal Medicine ,CREDENCE Trial Investigators ,medicine ,Diabetes Mellitus ,Science & Technology ,business.industry ,urogenital system ,diabetic nephropathy ,Type 2 Diabetes Mellitus ,KIDNEY-DISEASE ,medicine.disease ,chemistry ,business ,Kidney disease - Abstract
BACKGROUND: Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium-glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS: In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin-angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of
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- 2019
3. Bardoxolone Methyl in Type 2 Diabetes and Stage 4 Chronic Kidney Disease
- Author
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De Zeeuw, Dick, Akizawa, Tadao, Audhya, Paul, Bakris, George L., Chin, Melanie, Christ-Schmidt, Heidi, Goldsberry, Angie, Houser, Mark, Krauth, Melissa, Lambers Heerspink, Hiddo J., McMurray, John J., Meyer, Colin J., Parving, Hans-Henrik, Remuzzi, Giuseppe, Toto, Robert D., Vaziri, Nosratola D., Wanner, Christoph, Wittes, Janet, Wrolstad, Danielle, Chertow, Glenn M., Toto, B., McCullough, P., Ivanovich, P., Ketteler, M., Lachin, J., McGill, J., Agarwal, R., Anker, S., Arenillas, J. F., Januzzi, J., Jardine, A., Kasner, S., Kissela, B., Kolansky, D., Mann, J., Thadhani, R., Champion de Crespigny, P., Chan, D. T., D'Almeida, E., Fraser, I., Gray, N., Holt, S., Irish, A., Isbel, N., Kerr, P., Packham, D., Phoon, R., Pollock, C., Roger, S., Suranyi, M., Walker, R., Wittert, G., Yue, D., Balcke, P., Prager, R., Schernthaner, G., Sunder-Plassmann, G., Jadoul, M., Krzesinski, J. M., Peeters, P., Van der Niepen, P., Van Gaal, L., Van Vlem, B., Warling, X., Chow, S., Cournoyer, S., Dumas, R., Jolly, S., Levin, A., McMahon, A., Mehta, H., Ooi, T. C., Perkins, D., Roy, L., Sapir, D., Tam, P., Bartaskova, D., Hemzsky, L., Kubina, D., Szabo, M., Tesar, V., Combe, C., Faller, B., Fauvel, J. P., Halimi, J. M., Hourmant, M., Le Meur, Y., Urena-Torres, P., Zaoui, P., Al-Sarraf, S., Burst, V., Degenhardt, S., Kempe, H. P., Kleophas, W., Kosch, C., Krumme, B., Kuhlmann, M., Pistrosch, F., Rambausek, M., Schmidt-Guertler, H., Segiet, T., Sommerer, C., Vielhauer, V., Wanner, C., Beberashvili, I., Benchetrit, S., Herskovits, T., Karnieli, E., Levin-Iaina, N., Mosenzon, O., Tsur, A., van Dijk, D. J., Wainstein, J., Yagil, Y., Yerushalmi, Y., Colussi, G., Conte, G., Di Luca, M., Giovambatista, C., Messa, P., Pani, A., Pisani, A., Rapana, M. R., Ruggenenti, P., Villa, G., Zoccali, C., Correa-Rotter, R., Diaz-Escobedo, S. L., Garcia, P., Gonzalez Galvez, G., Obrador Vera, G. T., Rico, R., Calero, F., Cigarran, S., de Alvaro, F., de Francisco, A. L., Egido, J., Fernandez, E., Fernandez Vega, F., Fort, J., Galan Serrano, A., Gorriz Teruel, J. L., Martinez, I., Martinez Castelao, A., Munar, M. A., Navarro, J., Nieto, J., Osuna, A., Pascual, J., Portoles, J., Praga, M., Vallés, M., Fellstrom, B., Frisenette-Fich, C., Hadimeri, H., Stenvinkel, P., Svensson, M., Weiss, L., Adamson, K., Dornhorst, A., El Kossi, M., Gnudi, L., Hendry, B., Johnson, A., Joseph, F., Kalra, P., Marshall, S., Mikhail, A., Myint, K. S., Soran, H., Taal, M., Zehnder, D., Abbott, L., Acharya, A., Ahmed, Z., Aiello, J., Akom, M., Ali, S., Alzohaili, O., Anderson, L., Anderson, S., Anger, M., Appel, G., Arakaki, R. F., Arif, A., Assefi, A. R., Atray, N., Awad, A., Barranco, E., Belledonne, M. O., Belo, D., Bernardo, M., Bernstein, R., Bhalla, V., Bhatia, D., Black, R. M., Block, G., Blondin, J., Blumenthal, S. S., Bononi, P., Brantley, R. R., Bresssler, P., Broumand, V., Brusco, O., Buerkert, J., Burgos-Calderon, R., Campbell, R., Canas, G., Cangiano, J., Cherlin, R., Chilakapati, V., Comunale, R., Coyne, D., Crawford, P. W., Darwish, R., Deeb, W., Denker, P. S., Desai, S., Desouza, C., Diamond, S., Dixon, B. S., Durham, J. H., Eisner, G., Elder, J. G., El-Shahawy, M., Fadda, G., Fitz-Patrick, D., Fonseca, V., Fraser, N. J., Frei, G., Fried, L., Galindo-Ramos, E., Germain, M., Ghantous, W., Gilbert, J. M., Gillum, D., Godwin, J., Goel, A., Goldfarb, DS., Graf, R. J., Greenwood, T., Guasch, A., Hanna, A., Harper, K., Herman, T., Hilton, T., Hines, T., Hoggard, J., Hootkins, R., Huseman, R., Israelit, A., Jamal, A., Kant, K., Kaptein, E., Kathresal, A., Kaupke, J., Kaveh, K., Kaye, W., Keightley, G. E., Keith, K., Khairullah, Q., Kondle, V., Kopyt, N., Krishna, G., Lawrence, M. K., LeBeau, M., Leehey, D. J., Levine, M. M., Levinson, D., Lew, S. Q., Lewis, D., Linfert, D., Liss, K., Lund, R., Madeleine, P., Mahmood, K., Martin, E. R., Martinez, C., Mayeda, S. O., Mendez, R., Middleton, J., Molitch, M. E., Moncrief, J., Moustafa, M., Muoneke, R., Murray, A. V., Murugan, T. S., Nammour, T. M., Nassar, G., Navaneethan, S., Newman, J., Nossuli, A., Nwakoby, I., Osama, S., Ouseph, R., Parker, J., Parnes, E., Patel, N., Pergola, P., Perlman, A., Perry, R. G., Petrillo, R., Prabhakar, S., Purighalla, R. S., Quesada-Suarez, L., Rabiei, A., Raskin, P., Rastogi, A., Reisin, E., Rekhi, A., Rivera-Colon, L., Rizk, D., Rodelas, R., Roer, D., Rosas, S., Ross, D. L., Rovner, S., Sackel, H., Sader, S., Santos, P., Schmidt, R., Shafik, S., Shakeel, M., Sharon, Z., Silva, A. L., Silva, A., Singh, B., Smith, M., Solomon, R., Soman, S., Spinowitz, B., Sprague, S. M., Spry, L., Stonesifer, L., Streja, D., Suchinda, P., Sun, C., Thakar, C. V., Trespalacios, F., Tumlin, J. A., Van Buren, P., Vernace, M., Vicks, S., Warren, M., Weiss, D., Welker, J., Winston, J. A., Wombolt, D. G., Wood, M., Wu, M., Wynne, A., Yu, H., Zabaneh, R. I., Groningen Kidney Center (GKC), Methods in Medicines evaluation & Outcomes research (M2O), De Zeeuw, Dick, Akizawa, Tadao, Audhya, Paul, Bakris, George L., Chin, Melanie, Christ-Schmidt, Heidi, Goldsberry, Angie, Houser, Mark, Krauth, Melissa, Lambers Heerspink, Hiddo J., Mcmurray, John J., Meyer, Colin J., Parving, Hans-Henrik, Remuzzi, Giuseppe, Toto, Robert D., Vaziri, Nosratola D., Wanner, Christoph, Wittes, Janet, Wrolstad, Danielle, Chertow, Glenn M., Toto, B., Mccullough, P., Ivanovich, P., Ketteler, M., Lachin, J., Mcgill, J., Agarwal, R., Anker, S., Arenillas, J. F., Januzzi, J., Jardine, A., Kasner, S., Kissela, B., Kolansky, D., Mann, J., Thadhani, R., Champion de Crespigny, P., Chan, D. T., D'Almeida, E., Fraser, I., Gray, N., Holt, S., Irish, A., Isbel, N., Kerr, P., Packham, D., Phoon, R., Pollock, C., Roger, S., Suranyi, M., Walker, R., Wittert, G., Yue, D., Balcke, P., Prager, R., Schernthaner, G., Sunder-Plassmann, G., Jadoul, M., Krzesinski, J. M., Peeters, P., Van der Niepen, P., Van Gaal, L., Van Vlem, B., Warling, X., Chow, S., Cournoyer, S., Dumas, R., Jolly, S., Levin, A., Mcmahon, A., Mehta, H., Ooi, T. C., Perkins, D., Roy, L., Sapir, D., Tam, P., Bartaskova, D., Hemzsky, L., Kubina, D., Szabo, M., Tesar, V., Combe, C., Faller, B., Fauvel, J. P., Halimi, J. M., Hourmant, M., Le Meur, Y., Urena-Torres, P., Zaoui, P., Al-Sarraf, S., Burst, V., Degenhardt, S., Kempe, H. P., Kleophas, W., Kosch, C., Krumme, B., Kuhlmann, M., Pistrosch, F., Rambausek, M., Schmidt-Guertler, H., Segiet, T., Sommerer, C., Vielhauer, V., Wanner, C., Beberashvili, I., Benchetrit, S., Herskovits, T., Karnieli, E., Levin-Iaina, N., Mosenzon, O., Tsur, A., van Dijk, D. J., Wainstein, J., Yagil, Y., Yerushalmi, Y., Colussi, G., Conte, G., Di Luca, M., Giovambatista, C., Messa, P., Pani, A., Pisani, A., Rapana, M. R., Ruggenenti, P., Villa, G., Zoccali, C., Correa-Rotter, R., Diaz-Escobedo, S. L., Garcia, P., Gonzalez Galvez, G., Obrador Vera, G. T., Rico, R., Calero, F., Cigarran, S., de Alvaro, F., de Francisco, A. L., Egido, J., Fernandez, E., Fernandez Vega, F., Fort, J., Galan Serrano, A., Gorriz Teruel, J. L., Martinez, I., Martinez Castelao, A., Munar, M. A., Navarro, J., Nieto, J., Osuna, A., Pascual, J., Portoles, J., Praga, M., Vallés, M., Fellstrom, B., Frisenette-Fich, C., Hadimeri, H., Stenvinkel, P., Svensson, M., Weiss, L., Adamson, K., Dornhorst, A., El Kossi, M., Gnudi, L., Hendry, B., Johnson, A., Joseph, F., Kalra, P., Marshall, S., Mikhail, A., Myint, K. S., Soran, H., Taal, M., Zehnder, D., Abbott, L., Acharya, A., Ahmed, Z., Aiello, J., Akom, M., Ali, S., Alzohaili, O., Anderson, L., Anderson, S., Anger, M., Appel, G., Arakaki, R. F., Arif, A., Assefi, A. R., Atray, N., Awad, A., Barranco, E., Belledonne, M. O., Belo, D., Bernardo, M., Bernstein, R., Bhalla, V., Bhatia, D., Black, R. M., Block, G., Blondin, J., Blumenthal, S. S., Bononi, P., Brantley, R. R., Bresssler, P., Broumand, V., Brusco, O., Buerkert, J., Burgos-Calderon, R., Campbell, R., Canas, G., Cangiano, J., Cherlin, R., Chilakapati, V., Comunale, R., Coyne, D., Crawford, P. W., Darwish, R., Deeb, W., Denker, P. S., Desai, S., Desouza, C., Diamond, S., Dixon, B. S., Durham, J. H., Eisner, G., Elder, J. G., El-Shahawy, M., Fadda, G., Fitz-Patrick, D., Fonseca, V., Fraser, N. J., Frei, G., Fried, L., Galindo-Ramos, E., Germain, M., Ghantous, W., Gilbert, J. M., Gillum, D., Godwin, J., Goel, A., Goldfarb, Ds., Graf, R. J., Greenwood, T., Guasch, A., Hanna, A., Harper, K., Herman, T., Hilton, T., Hines, T., Hoggard, J., Hootkins, R., Huseman, R., Israelit, A., Jamal, A., Kant, K., Kaptein, E., Kathresal, A., Kaupke, J., Kaveh, K., Kaye, W., Keightley, G. E., Keith, K., Khairullah, Q., Kondle, V., Kopyt, N., Krishna, G., Lawrence, M. K., Lebeau, M., Leehey, D. J., Levine, M. M., Levinson, D., Lew, S. Q., Lewis, D., Linfert, D., Liss, K., Lund, R., Madeleine, P., Mahmood, K., Martin, E. R., Martinez, C., Mayeda, S. O., Mendez, R., Middleton, J., Molitch, M. E., Moncrief, J., Moustafa, M., Muoneke, R., Murray, A. V., Murugan, T. S., Nammour, T. M., Nassar, G., Navaneethan, S., Newman, J., Nossuli, A., Nwakoby, I., Osama, S., Ouseph, R., Parker, J., Parnes, E., Patel, N., Pergola, P., Perlman, A., Perry, R. G., Petrillo, R., Prabhakar, S., Purighalla, R. S., Quesada-Suarez, L., Rabiei, A., Raskin, P., Rastogi, A., Reisin, E., Rekhi, A., Rivera-Colon, L., Rizk, D., Rodelas, R., Roer, D., Rosas, S., Ross, D. L., Rovner, S., Sackel, H., Sader, S., Santos, P., Schmidt, R., Shafik, S., Shakeel, M., Sharon, Z., Silva, A. L., Silva, A., Singh, B., Smith, M., Solomon, R., Soman, S., Spinowitz, B., Sprague, S. M., Spry, L., Stonesifer, L., Streja, D., Suchinda, P., Sun, C., Thakar, C. V., Trespalacios, F., Tumlin, J. A., Van Buren, P., Vernace, M., Vicks, S., Warren, M., Weiss, D., Welker, J., Winston, J. A., Wombolt, D. G., Wood, M., Wu, M., Wynne, A., Yu, H., Zabaneh, R. I., de Zeeuw, D, Akizawa, T, Audhya, P, Bakris, Gl, Chin, M, Christ Schmidt, H, Goldsberry, A, Houser, M, Krauth, M, Lambers Heerspink, Hj, Mcmurray, Jj, Meyer, Cj, Parving, Hh, Remuzzi, G, Toto, Rd, Vaziri, Nd, Wanner, C, Wittes, J, Wrolstad, D, Chertow, Gm, Pisani, Antonio, De Zeeuw, D, Bakris, G, Lambers Heerspink, H, Mcmurray, J, Meyer, C, Parving, H, Toto, R, Vaziri, N, and Chertow, G.
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Male ,medicine.medical_specialty ,Intention to Treat Analysi ,NF-E2-Related Factor 2 ,NEPHROPATHY ,Urology ,Renal function ,Kaplan-Meier Estimate ,Type 2 diabetes ,Placebo ,Article ,Nephropathy ,NRF2 ,Double-Blind Method ,Cardiovascular Disease ,Diabetes mellitus ,Internal medicine ,medicine ,CKD ,Treatment Failure ,Bardoxolone methyl ,Oleanolic Acid ,Renal Insufficiency, Chronic ,Aged ,OUTCOMES ,IRBESARTAN ,ANALOGS ,business.industry ,Medicine (all) ,Hazard ratio ,General Medicine ,Middle Aged ,medicine.disease ,Weight Lo ,Endocrinology ,Diabetes Mellitus, Type 2 ,Diabetic Nephropathie ,Kidney Failure, Chronic ,Female ,TRIAL ,Stage 4 chronic kidney disease ,business ,Glomerular Filtration Rate ,Human ,RENAL EVENTS BEACON - Abstract
Background: Although inhibitors of the renin–angiotensin–aldosterone system can slow the progression of diabetic kidney disease, the residual risk is high. Whether nuclear 1 factor (erythroid-derived 2)–related factor 2 activators further reduce this risk is unknown. Methods: We randomly assigned 2185 patients with type 2 diabetes mellitus and stage 4 chronic kidney disease (estimated glomerular filtration rate [GFR], 15 to < 30 ml per minute per 1.73 m2 of body-surface area) to bardoxolone methyl, at a daily dose of 20 mg, or placebo. The primary composite outcome was end-stage renal disease (ESRD) or death from cardiovascular causes. Results: The sponsor and the steering committee terminated the trial on the recommendation of the independent data and safety monitoring committee; the median follow-up was 9 months. A total of 69 of 1088 patients (6%) randomly assigned to bardoxolone methyl and 69 of 1097 (6%) randomly assigned to placebo had a primary composite outcome (hazard ratio in the bardoxolone methyl group vs. the placebo group, 0.98; 95% confidence interval [CI], 0.70 to 1.37; P=0.92). In the bardoxolone methyl group, ESRD developed in 43 patients, and 27 patients died from cardiovascular causes; in the placebo group, ESRD developed in 51 patients, and 19 patients died from cardiovascular causes. A total of 96 patients in the bardoxolone methyl group were hospitalized for heart failure or died from heart failure, as compared with 55 in the placebo group (hazard ratio, 1.83; 95% CI, 1.32 to 2.55; P < 0.001). Estimated GFR, blood pressure, and the urinary albumin-to-creatinine ratio increased significantly and body weight decreased significantly in the bardoxolone methyl group, as compared with the placebo group. Conclusions: Among patients with type 2 diabetes mellitus and stage 4 chronic kidney disease, bardoxolone methyl did not reduce the risk of ESRD or death from cardiovascular causes. A higher rate of cardiovascular events with bardoxolone methyl than with placebo prompted termination of the trial. (Funded by Reata Pharmaceuticals; BEACON ClinicalTrials.gov number, NCT01351675.)
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- 2013
4. Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease
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De Zeeuw, D, Akizawa, T, Audhya, P, Bakris, GL, Chin, M, Christ-Schmidt, H, Goldsberry, A, Houser, M, Krauth, M, Lambers Heerspink, HJ, McMurray, JJ, Meyer, CJ, Parving, HH, Remuzzi, G, Toto, RD, Vaziri, ND, Wanner, C, Wittes, J, Wrolstad, D, Chertow, GM, Toto, B, McCullough, P, Ivanovich, P, Ketteler, M, Lachin, J, McGill, J, Agarwal, R, Anker, S, Arenillas, JF, Januzzi, J, Jardine, A, Kasner, S, Kissela, B, Kolansky, D, Mann, J, Thadhani, R, Champion de Crespigny, P, Chan, DT, D'Almeida, E, Fraser, I, Gray, N, Holt, S, Irish, A, Isbel, N, Kerr, P, Packham, D, Phoon, R, Pollock, C, Roger, S, Suranyi, M, Walker, R, Wittert, G, Yue, D, Balcke, P, Prager, R, Schernthaner, G, Sunder-Plassmann, G, Jadoul, M, Krzesinski, JM, Peeters, P, Van der Niepen, P, Van Gaal, L, Van Vlem, B, Warling, X, Chow, S, Cournoyer, S, Dumas, R, Jolly, S, Levin, A, McMahon, A, Mehta, H, Ooi, TC, Perkins, D, Roy, L, Sapir, D, Tam, P, Bartaskova, D, Hemzsky, L, Kubina, D, Szabo, M, Tesar, V, Combe, C, Faller, B, Fauvel, JP, Halimi, JM, Hourmant, M, Le Meur, Y, Urena-Torres, P, Zaoui, P, Al-Sarraf, S, Burst, V, Degenhardt, S, Kempe, HP, Kleophas, W, Kosch, C, Krumme, B, Kuhlmann, M, Pistrosch, F, and Rambausek, M
- Abstract
BACKGROUND: Although inhibitors of the renin-angiotensin-aldosterone system can slow the progression of diabetic kidney disease, the residual risk is high. Whether nuclear 1 factor (erythroid-derived 2)-related factor 2 activators further reduce this risk is unknown. METHODS: We randomly assigned 2185 patients with type 2 diabetes mellitus and stage 4 chronic kidney disease (estimated glomerular filtration rate [GFR], 15 to
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- 2013
- Full Text
- View/download PDF
5. Safety and feasibility of liver-directed ex vivo gene therapy for homozygous familial hypercholesterolemia
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Raper, S E, Grossman, M, Rader, D J, Thoene, J G, Clark, B J, Kolansky, D M, Muller, D W, and Wilson, J M
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Research Article - Abstract
OBJECTIVE: The purpose of this report was to provide detailed information on the safety and feasibility of surgical procedures associated with the first ex vivo liver-directed gene therapy trial for the treatment of vivo gene therapy for homozygous familial hypercholesterolemia (FH). SUMMARY BACKGROUND DATA: Familial hypercholesterolemia is an autosomal dominant disease in which the gene encoding the low density lipoprotein receptor is defective. Patients homozygous for this mutation have extraordinarily high levels of cholesterol and accelerated atherosclerosis and die prematurely of myocardial infarction. The concept of liver-directed gene therapy was based on the report of normalization of cholesterol levels by orthotopic cardiac/liver transplant in a child with homozygous FH. METHODS: Five patients with homozygous FH were selected for inclusion in this trial. The patients underwent hepatic resection and placement of a portal venous catheter. Primary hepatocytes cultures were prepared from the resected liver and transduced with a recombinant retrovirus encoding the gene for the human low density lipoprotein receptor. The genetically modified cells were then transplanted into the liver through the portal venous catheter. RESULTS: Numerous clinical, laboratory, and radiologic parameters were analyzed. Elevations of the hepatic transaminases and leukocyte counts and a decline in hematocrit count were noted. Transient elevations of the portal pressure were observed during cell infusion. No major perioperative morbidity--specifically, myocardial infarct, perioperative hemorrhage, or portal vein thrombosis--or death occurred as a result of this protocol. CONCLUSION: Liver-directed ex vivo gene therapy can be accomplished safely in humans and is appropriate for selected patients.
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- 1996
6. Factors associated with Percutaneous Coronary Intervention (PCI) access complications
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Hoke, L., Ratcliffe, S., Kimmel, S., and Kolansky, D.
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Coronary heart disease -- Causes of -- Research ,Intensive care units -- Services -- Research ,Health ,Health care industry ,Research ,Services ,Causes of - Abstract
Purpose: To determine what method for sheath removal produces the fewest complications and what factors are associated with access site complications. Background/Significance: Complex antiplatelet and antithrombotic regimens used in conjunction [...]
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- 2007
7. Gene therapy for ischemic heart disease.
- Author
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Malosky, Steven, Kolansky, Daniel M., Malosky, S, and Kolansky, D M
- Published
- 1996
- Full Text
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8. Energy-dependent translocation of the precursor of ornithine transcarbamylase by isolated rat liver mitochondria.
- Author
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Kolansky, D M, Conboy, J G, Fenton, W A, and Rosenberg, L E
- Published
- 1982
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9. Predictors of clinical outcome following percutaneous intervention for in-stent restenosis.
- Author
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Klugherz, Bruce D., Meneveau, Nicolas F., Klugherz, B D, Meneveau, N F, Kolansky, D M, Herrmann, H C, Schiele, F, Matthai, W H Jr, Groh, W C, Untereker, W J, Hirshfeld, J W Jr, Bassand, J P, and Wilensky, R L
- Subjects
- *
CORONARY artery stenosis , *CARDIAC surgery - Abstract
Percutaneous intervention for the first episode of in-stent restenosis was performed in 177 patients 5.4 +/- 0.3 months after native coronary stent implantation. Medical records were reviewed and patients contacted 13.3 +/- 1.2 months after in-stent intervention to ascertain the subsequent clinical course. The effects of demographic, procedural, and angiographic variables on clinical outcomes were determined. At 2 years, Kaplan-Meier estimated survival was 93 +/- 3% and freedom from death, myocardial infarction, and a third target artery revascularization (TAR) was 67 +/- 4%. The actuarial frequency of a third TAR was 26 +/- 4% at 1 year. Stratification of outcomes according to timing of in-stent intervention revealed an approximate twofold higher frequency of adverse events among patients with early (=3 months) in-stent restenosis. Advanced age (p = 0.019), prior coronary bypass (p = 0. 017), and early in-stent intervention (p = 0.006) independently predicted increased mortality at follow-up. Systemic hypertension (p = 0.004), diabetes mellitus (p = 0.044), and early in-stent intervention (p <0.0001) independently predicted a third TAR. These variables (p = 0.007, p = 0.027, and p <0.0001, respectively) also independently predicted a composite end point consisting of death, myocardial infarction, and a third TAR. No angiographic variable predicted outcome after in-stent intervention. Thus, long-term outcome following in-stent intervention was favorable. Early in-stent intervention, advanced age, hypertension, and diabetes predicted adverse outcomes. [ABSTRACT FROM AUTHOR]
- Published
- 2000
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10. Effect of Electronic Reminders, Financial Incentives, and Social Support on Outcomes After Myocardial Infarction: The HeartStrong Randomized Clinical Trial.
- Author
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Volpp KG, Troxel AB, Mehta SJ, Norton L, Zhu J, Lim R, Wang W, Marcus N, Terwiesch C, Caldarella K, Levin T, Relish M, Negin N, Smith-McLallen A, Snyder R, Spettell CM, Drachman B, Kolansky D, and Asch DA
- Subjects
- Aftercare economics, Aftercare methods, Aftercare organization & administration, Aged, Female, Humans, Male, Medicare, Medication Therapy Management organization & administration, Middle Aged, Outcome and Process Assessment, Health Care, Social Support, United States, Adrenergic beta-Antagonists economics, Adrenergic beta-Antagonists therapeutic use, Aspirin economics, Aspirin therapeutic use, Hydroxymethylglutaryl-CoA Reductase Inhibitors economics, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Motivation, Myocardial Infarction drug therapy, Myocardial Infarction economics, Myocardial Infarction psychology, Platelet Aggregation Inhibitors economics, Platelet Aggregation Inhibitors therapeutic use, Reminder Systems economics, Reminder Systems statistics & numerical data
- Abstract
Importance: Adherence to medications prescribed after acute myocardial infarction (AMI) is low. Wireless technology and behavioral economic approaches have shown promise in improving health behaviors., Objective: To determine whether a system of medication reminders using financial incentives and social support delays subsequent vascular events in patients following AMI compared with usual care., Design, Setting, and Participants: Two-arm, randomized clinical trial with a 12-month intervention conducted from 2013 through 2016. Investigators were blinded to study group, but participants were not. Design was a health plan-intermediated intervention for members of several health plans. We recruited 1509 participants from 7179 contacted AMI survivors (insured with 5 large US insurers nationally or with Medicare fee-for-service at the University of Pennsylvania Health System). Patients aged 18 to 80 years were eligible if currently prescribed at least 2 of 4 study medications (statin, aspirin, β-blocker, antiplatelet agent), and were hospital inpatients for 1 to 180 days and discharged home with a principal diagnosis of AMI., Interventions: Patients were randomized 2:1 to an intervention using electronic pill bottles combined with lottery incentives and social support for medication adherence (1003 patients), or to usual care (506 patients)., Main Outcomes and Measures: Primary outcome was time to first vascular rehospitalization or death. Secondary outcomes were time to first all-cause rehospitalization, total number of repeated hospitalizations, medication adherence, and total medical costs., Results: A total of 35.5% of participants were female (n = 536); mean (SD) age was 61.0 (10.3) years. There were no statistically significant differences between study arms in time to first rehospitalization for a vascular event or death (hazard ratio, 1.04; 95% CI, 0.71 to 1.52; P = .84), time to first all-cause rehospitalization (hazard ratio, 0.89; 95% CI, 0.73 to 1.09; P = .27), or total number of repeated hospitalizations (hazard ratio, 0.94; 95% CI, 0.60 to 1.48; P = .79). Mean (SD) medication adherence did not differ between control (0.42 [0.39]) and intervention (0.46 [0.39]) (difference, 0.04; 95% CI, -0.01 to 0.09; P = .10). Mean (SD) medical costs in 12 months following enrollment did not differ between control ($29 811 [$74 850]) and intervention ($24 038 [$66 915]) (difference, -$5773; 95% CI, -$13 682 to $2137; P = .15)., Conclusions and Relevance: A compound intervention integrating wireless pill bottles, lottery-based incentives, and social support did not significantly improve medication adherence or vascular readmission outcomes for AMI survivors., Trial Registration: clinicaltrials.gov Identifier: NCT01800201.
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- 2017
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11. Haemodynamic management strategies are not explicitly defined in the majority of therapeutic hypothermia implementation studies.
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Gaieski DF, Neumar RW, Fuchs B, Abella BS, Kolansky D, Delfin G, Leary M, and Goyal M
- Subjects
- Adult, Coma etiology, Coma physiopathology, Disease Management, Heart Arrest complications, Heart Arrest physiopathology, Humans, Treatment Outcome, Coma therapy, Heart Arrest therapy, Hemodynamics, Hypothermia, Induced methods, Resuscitation methods
- Abstract
Background: Therapeutic hypothermia (TH) has revolutionized the management of comatose post-cardiac arrest syndrome (PCAS) patients. The 2008 ILCOR/AHA Consensus Statement for the treatment of PCAS suggests that goal-directed therapy, targeting mean arterial pressure (MAP), central venous pressure (CVP), and central venous oxygen saturation (ScvO(2)), should be employed to normalize oxygen delivery. However, the optimal PCAS haemodynamic management strategy has not been defined and few objective data exist to guide clinicians., Objective: To describe the haemodynamic strategies used in TH implementation studies., Methods: A Medline search (time period, 3/2002 to 3/2010) was performed using the terms cardiac arrest and hypothermia, induced, then limited post-search to implementation studies of TH in comatose adults. The identified studies were examined for explicit definitions of the following terms: MAP; systolic blood pressure (SBP), CVP, ScvO(2), pulmonary artery catheter (PAC), echocardiogram (ECHO), lactate, and volume status., Results: Forty-four implementation studies were identified and 43% (19/44) of them mentioned haemodynamics in any fashion. At least one haemodynamic goal was specifically defined in 16/44 (36%). The median number defined was 4 (range 1-6); individual goals as follows: MAP, 13/44 (30%); SBP, 3/44 (7%); CVP, 5/44 (11%); ScvO(2), 4/44 (9%); PAC, 7/44 (16%); ECHO, 7/44 (16%); lactate, 5/44 (11%); and volume status, 8/44 (18%)., Conclusions: Specific haemodynamic goals are defined in a minority of published TH implementation studies. Given the volatile haemodynamics of the PCAS and lack of consensus on an optimal resuscitation strategy, explicit description of haemodynamic goals should be provided in future studies., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2012
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12. Patient satisfaction is comparable to early discharge versus overnight observation after elective percutaneous coronary intervention.
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Glaser R, Gertz Z, Matthai WH, Wilensky RL, Weiner M, Kolansky D, Hirshfeld J Jr, and Herrmann H
- Subjects
- Cost-Benefit Analysis, Female, Follow-Up Studies, Health Surveys, Humans, Length of Stay, Male, Middle Aged, Pilot Projects, Prospective Studies, Retrospective Studies, Surveys and Questionnaires, Time Factors, Angioplasty, Balloon, Coronary, Coronary Artery Disease therapy, Myocardial Infarction therapy, Patient Discharge economics, Patient Satisfaction
- Abstract
Background: Previous investigation has suggested that early discharge after percutaneous coronary intervention (PCI) is feasible and safe, but these studies have utilized largely radial approaches or been conducted in non-U.S. cohorts. We sought to assess patient satisfaction, safety and cost of a strategy of selective early discharge in U.S. patients undergoing PCI via a femoral approach with contemporary adjunctive pharmacologic and hemostasis agents., Methods and Results: Patients with stable coronary artery disease undergoing elective PCI were prospectively recruited and randomized to either routine care, with an overnight hospital stay, versus early discharge 2 hours following successful PCI with adjunctive bivalirudin therapy and a femoral arterial closure device at the end of the procedure. The primary endpoints were safety and patient satisfaction as measured by a validated patient satisfaction survey during the index hospital stay and at 30 days. A total of 39 patients were randomized, with 20 to routine care and 19 to early discharge. There was no difference in major safety endpoints including death, non-fatal MI, urgent target lesion revascularization and thrombolysis in myocardial infarction (TIMI) major bleeding, with none in either group. Mean patient satisfaction scores were similar and high in both groups (89.6 for early discharge patients and 90.7 for routine care patients, p = 0.68). There was lower cost in the early discharge group, with a mean cost of 8,604 USD versus 10,565 USD in the routine care group (mean difference 1,961 USD, 95% confidence interval, -96 USD to 4,017 USD)., Conclusion: Patients undergoing elective PCI for stable coronary artery disease may have similar safety and satisfaction with early discharge when using a careful strategy that incorporates optimal stent and hemostasis results and contemporary adjunctive anticoagulation therapy, with lower cost. This strategy may serve as a basis for a larger-scale randomized trial.
- Published
- 2009
13. Acute myocardial infarction following a negative evaluation of chest pain.
- Author
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Varada R, Manaker S, Rohrbach J, and Kolansky D
- Subjects
- Acute Disease, Adult, Aged, Cardiology Service, Hospital statistics & numerical data, Child, Diagnostic Errors, Emergency Service, Hospital statistics & numerical data, Follow-Up Studies, Guideline Adherence, Hospitals, University standards, Hospitals, University statistics & numerical data, Humans, Infant, Middle Aged, Myocardial Infarction epidemiology, Myocardial Infarction physiopathology, Patient Admission statistics & numerical data, Patient Readmission statistics & numerical data, Pennsylvania epidemiology, Risk Factors, Cardiology Service, Hospital standards, Chest Pain etiology, Diagnostic Techniques and Procedures statistics & numerical data, Emergency Service, Hospital standards, Medical Audit, Myocardial Infarction diagnosis
- Abstract
Although acute chest pain accounts for five million emergency room visits annually, only 10% represent acute myocardial infarctions (AMI). Even patients with negative evaluations of chest symptoms experience subsequent cardiac events. Patients readmitted with AMI within 90 days after a cardiac evaluation were examined to identify potential errors in management that may have Led to readmission. Only six of 2,340 patients met criteria for AMI after a negative work-up. No medical errors were found to account for the subsequent AMI. No other previously published reports have investigated the quality of chest pain evaluations to find missed opportunities for cardiac event prevention.
- Published
- 2005
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14. Combination therapy with clopidogrel and aspirin after coronary stenting.
- Author
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Kolansky DM, Klugherz BD, Curran SC, Herrmann HC, Magness K, Wilensky RL, and Hirshfeld JW Jr
- Subjects
- Aspirin administration & dosage, Clopidogrel, Drug Therapy, Combination, Female, Humans, Male, Middle Aged, Platelet Aggregation Inhibitors administration & dosage, Ticlopidine administration & dosage, Ticlopidine therapeutic use, Treatment Outcome, Aspirin therapeutic use, Coronary Disease therapy, Platelet Aggregation Inhibitors therapeutic use, Stents, Thrombosis prevention & control, Ticlopidine analogs & derivatives
- Abstract
Combination antiplatelet therapy using aspirin and ticlopidine has been the standard of care for prevention of subacute thrombosis following coronary stent implantation. However, the use of ticlopidine is associated with a significant risk of adverse hematologic side effects. Clopidogrel is an inhibitor of ADP-induced platelet aggregation that has a better safety profile than ticlopidine. We examined the 30-day clinical outcome following coronary stent implantation in 253 consecutive patients treated with clopidogrel and aspirin. Follow-up was achieved in 99% of patients and four adverse events were documented. Two patients had angiographically confirmed subacute stent thrombosis (0.8%), and both of these patients underwent successful repeat angioplasty at the stent site. There were two patient deaths during follow-up (0. 8%). One was sudden within 1 week of stent placement and the other occurred in a patient with multisystem organ failure after an extensive myocardial infarction that antedated the stent procedure, with no clinical evidence for stent thrombosis. The combined frequency of subacute stent thrombosis and death was 1.6%. This is comparable to prior studies using the combination of ticlopidine and aspirin following stenting. Therefore, clopidogrel in combination with aspirin appears to be a safe and effective therapy in the prevention of subacute thrombosis following coronary stent implantation.
- Published
- 2000
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15. Operator volume as a "risk factor".
- Author
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Kimmel SE and Kolansky DM
- Subjects
- Angioplasty, Balloon, Coronary standards, Humans, Outcome Assessment, Health Care, Risk Factors, Angioplasty, Balloon, Coronary adverse effects, Angioplasty, Balloon, Coronary statistics & numerical data, Clinical Competence statistics & numerical data, Practice Patterns, Physicians' standards
- Published
- 1997
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16. Comparison of outcome after stenting for de novo versus restenotic narrowings in native coronary arteries.
- Author
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Mittal S, Weiss DL, Hirshfeld JW Jr, Kolansky DM, and Herrmann HC
- Subjects
- Adult, Angina Pectoris, Coronary Angiography, Disease-Free Survival, Female, Follow-Up Studies, Humans, Male, Middle Aged, Multivariate Analysis, Recurrence, Retrospective Studies, Risk Factors, Treatment Outcome, Angioplasty, Balloon, Coronary, Coronary Disease therapy, Stents
- Abstract
Intracoronary stenting of de novo narrowings results in a lower restenosis rate when compared with percutaneous transluminal coronary angioplasty. We sought to determine whether intracoronary stenting for restenotic narrowings is associated with a worse outcome when compared with stenting for de novo narrowings. A total of 114 consecutive patients with 124 narrowings were retrospectively identified. Stents were deployed in 46 de novo (37%) and in 78 restenotic (63%) narrowings. The 2 groups were similar with respect to variables known to affect restenosis. Follow-up angiograms were available in 88% of patients at a mean of 6.3 +/- 3.3 months after stent implantation. At follow-up angiography, a significantly higher restenosis rate in the restenotic group was observed (p = 0.05). Restenosis risk could not be predicted from variables known at the time of stent implantation. However, the presence of angina at the time of follow-up was significantly associated with restenosis (p = 0.01). Kaplan-Meier survival curves for freedom from repeat target-site revascularization demonstrated a significant difference in the need for target-site revascularization between the de novo and restenotic groups over the first-year post-stent implantation (p = 0.01; relative risk = 1.94). Multivariate analysis identified restenosis as the indication for stenting (p <0.01), postprocedure percent stenosis (p = 0.01), and narrowing length (p = 0.01) as independent predictors for repeat target-site revascularization. When compared with de novo narrowings, restenotic narrowings have a worse outcome after stenting. A prospective, randomized trial comparing outcome after percutaneous transluminal coronary angioplasty and stents for restenotic narrowings would be useful.
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- 1997
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17. Single coronary artery: an angiographic and MRI case report.
- Author
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Passman RS, Ferrari VA, Holland GA, Herling IM, and Kolansky DM
- Subjects
- Coronary Angiography, Coronary Vessel Anomalies complications, Female, Humans, Magnetic Resonance Imaging, Middle Aged, Coronary Vessel Anomalies diagnosis
- Abstract
A single coronary artery is a rare cause of cardiac ischemia, congestive heart failure, and sudden death. We report the second known antemortem diagnosis of a single right coronary artery supplying the entire myocardium.
- Published
- 1997
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18. Three-year clinical follow-up after Palmaz-Schatz stenting.
- Author
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Klugherz BD, DeAngelo DL, Kim BK, Herrmann HC, Hirshfeld JW, and Kolansky DM
- Subjects
- Aged, Angioplasty, Balloon, Coronary methods, Coronary Disease physiopathology, Female, Follow-Up Studies, Humans, Male, Middle Aged, Coronary Disease therapy, Stents
- Abstract
Objectives: Our goals were to examine late clinical outcome in a cohort of patients who electively received Palmaz-Schatz intracoronary stents, to identify specific predictors of outcome and to determine the time course of the development of ischemic cardiac events after stenting., Background: Short-term results of Palmaz-Schatz intracoronary stenting have been promising, with a reduction in both angiographic restenosis and clinical cardiac events up to 1 year after stenting., Methods: We analyzed the clinical outcomes in 65 consecutive patients who underwent stenting at least 3 years before analysis. Demographic, clinical and procedural predictors of survival and event-free survival, defined as freedom from myocardial infarction, stent-site percutaneous transluminal coronary angioplasty, coronary artery bypass graft surgery or death, were analyzed at a mean follow-up of 39 +/- 17 months., Results: Absolute survival and event-free survival at 3 years were 88% and 56%, respectively. Three-year freedom from stent-site revascularization was 66%. Predictors of decreased long-term survival (p < 0.05) included diabetes and a high angina score (Canadian Cardiovascular Society class III/IV) at 6 and 12 months after stenting. Predictors of decreased event-free survival (p < 0.05) included a high angina score at 3, 6 and 12 months after stenting, smaller stent deployment balloon size and greater number of stents implanted. Freedom from adverse events by 6 months after stenting also correlated with long-term event-free survival. Eighty-five percent of stent-site revascularizations occurred within 1 year. During late follow-up (>24 months), no patients had stent-site stenoses requiring revascularization, whereas 11% of patients required revascularization in nonstented coronary segments., Conclusions: Clinical predictors of worse long-term outcome included diabetes mellitus, higher angina score at follow-up, smaller stent deployment balloon size and greater number of stents at implantation. During follow-up, the majority of adverse events and stent-site revascularizations occurred early after stenting, and disease progression in nonstented vessels accounted for the majority of late revascularization events.
- Published
- 1996
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19. Femoral artery hemostasis using an implantable device (Angio-Seal) after coronary angioplasty.
- Author
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Kussmaul WG, Buchbinder M, Whitlow PL, Aker UT, Heuser RR, King SB, Kent KM, Leon MB, Kolansky DM, and Sandza JG
- Subjects
- Aged, Equipment Failure, Female, Humans, Male, Middle Aged, Treatment Outcome, Angioplasty, Balloon, Coronary instrumentation, Coronary Disease therapy, Femoral Artery, Hemostatic Techniques instrumentation, Prostheses and Implants
- Abstract
Coronary catheter interventional procedures are associated with risk of access site complications. We report our experience with Angio-Seal, an implantable hemostasis device, when used in the femoral artery after coronary angioplasty procedures. Sixty-eight patients were studied. Their average age was 63 years; 84% of the patients were male. All had 8 French access sheaths and received bolus heparin (mean dose 12,690 U). The arterial sheaths were removed an average of 455 min after the conclusion of the procedure, when the activated clotting time was 220 +/- 94 sec (range 97-503 sec). The hemostasis device was successfully deployed in 63 patients (93%). The average time to achieve complete arterial hemostasis was 4.4 +/- 8.9 min (range 0-45). Immediate, total hemostasis without requiring any form of external pressure was obtained in 37 of these patients (54%). the incidence of complications was as follows: significant bleeding occurred in 9 patients (13%); there were 2 hematomas (3%); there were no vascular or infectious complications. One device embolization occurred when the connecting suture broke and the intravascular anchor was lost; no clinical sequelae resulted, and manual hemostasis was successful. In four other patients, the device did not deploy and was removed entirely, followed by uneventful manual hemostasis. Follow-up for 2 months revealed no late sequelae in any patient, and complete absorption of the device was documented by ultrasound study in all cases. We conclude that this implantable device can achieve arterial hemostasis quickly and safety when used in anticoagulated patients after coronary interventional procedures.
- Published
- 1996
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20. Safety and feasibility of liver-directed ex vivo gene therapy for homozygous familial hypercholesterolemia.
- Author
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Raper SE, Grossman M, Rader DJ, Thoene JG, Clark BJ 3rd, Kolansky DM, Muller DW, and Wilson JM
- Subjects
- Adult, Canada ethnology, Child, China ethnology, Colombia ethnology, Combined Modality Therapy, Cyprus ethnology, Feasibility Studies, Female, Hepatectomy, Humans, Hyperlipoproteinemia Type II ethnology, Hyperlipoproteinemia Type II therapy, Liver, Male, Genetic Therapy methods, Homozygote, Hyperlipoproteinemia Type II genetics
- Abstract
Objective: The purpose of this report was to provide detailed information on the safety and feasibility of surgical procedures associated with the first ex vivo liver-directed gene therapy trial for the treatment of vivo gene therapy for homozygous familial hypercholesterolemia (FH)., Summary Background Data: Familial hypercholesterolemia is an autosomal dominant disease in which the gene encoding the low density lipoprotein receptor is defective. Patients homozygous for this mutation have extraordinarily high levels of cholesterol and accelerated atherosclerosis and die prematurely of myocardial infarction. The concept of liver-directed gene therapy was based on the report of normalization of cholesterol levels by orthotopic cardiac/liver transplant in a child with homozygous FH., Methods: Five patients with homozygous FH were selected for inclusion in this trial. The patients underwent hepatic resection and placement of a portal venous catheter. Primary hepatocytes cultures were prepared from the resected liver and transduced with a recombinant retrovirus encoding the gene for the human low density lipoprotein receptor. The genetically modified cells were then transplanted into the liver through the portal venous catheter., Results: Numerous clinical, laboratory, and radiologic parameters were analyzed. Elevations of the hepatic transaminases and leukocyte counts and a decline in hematocrit count were noted. Transient elevations of the portal pressure were observed during cell infusion. No major perioperative morbidity--specifically, myocardial infarct, perioperative hemorrhage, or portal vein thrombosis--or death occurred as a result of this protocol., Conclusion: Liver-directed ex vivo gene therapy can be accomplished safely in humans and is appropriate for selected patients.
- Published
- 1996
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21. A pilot study of ex vivo gene therapy for homozygous familial hypercholesterolaemia.
- Author
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Grossman M, Rader DJ, Muller DW, Kolansky DM, Kozarsky K, Clark BJ 3rd, Stein EA, Lupien PJ, Brewer HB Jr, and Raper SE
- Subjects
- Adult, Antibody Formation, Cell Transplantation, Cells, Cultured, Child, Cholesterol blood, Female, Follow-Up Studies, Gene Transfer Techniques, Genetic Vectors, Heterozygote, Humans, In Situ Hybridization, Lipids blood, Lipoproteins, LDL blood, Liver cytology, Male, Pilot Projects, Receptors, LDL immunology, Treatment Outcome, Genetic Therapy methods, Hyperlipoproteinemia Type II therapy, Receptors, LDL genetics
- Abstract
The outcome of the first pilot study of liver-directed gene therapy is reported here. Five patients with homozygous familial hypercholesterolaemia (FH) ranging in age from 7 to 41 years were enrolled; each patient tolerated the procedure well without significant complications. Transgene expression was detected in a limited number of hepatocytes of liver tissue harvested four months after gene transfer from all five patients. Significant and prolonged reductions in low density lipoprotein (LDL) cholesterol were demonstrated in three of five patients; in vivo LDL catabolism was increased 53% following gene therapy in a receptor negative patient, who realized a reduction in serum LDL equal to approximately 150 mg dl-1. This study demonstrates the feasibility of engrafting limited numbers of retrovirus-transduced hepatocytes without morbidity and achieving persistent gene expression lasting at least four months after gene therapy. The variable metabolic responses observed following low-level genetic reconstitution in the five patients studied precludes a broader application of liver-directed gene therapy without modifications that consistently effect substantially greater gene transfer.
- Published
- 1995
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22. Rapid arterial hemostasis and decreased access site complications after cardiac catheterization and angioplasty: results of a randomized trial of a novel hemostatic device.
- Author
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Kussmaul WG 3rd, Buchbinder M, Whitlow PL, Aker UT, Heuser RR, King SB, Kent KM, Leon MB, Kolansky DM, and Sandza JG Jr
- Subjects
- Aneurysm, False diagnostic imaging, Aneurysm, False prevention & control, Biocompatible Materials, Collagen, Equipment Design, Female, Femoral Artery diagnostic imaging, Hematoma diagnostic imaging, Hematoma prevention & control, Hemorrhage diagnostic imaging, Hemorrhage prevention & control, Heparin therapeutic use, Humans, Male, Middle Aged, Pressure, Sex Factors, Time Factors, Ultrasonography, Doppler, Duplex, Angioplasty, Balloon, Coronary, Cardiac Catheterization, Hemostatic Techniques instrumentation
- Abstract
Objectives: This study was performed to test the safety and efficacy of a novel bioabsorbable hemostatic puncture closure device deployed through an arterial sheath., Background: Cardiac catheterization procedures are associated with a risk of complications at the arterial access site. Increasing numbers of interventional procedures requiring large sheaths or intense anticoagulation underline the need for secure, rapid methods of obtaining hemostasis at the time of sheath removal., Methods: We conducted a randomized, multicenter trial in 435 patients undergoing cardiac catheterization or angioplasty at eight participating centers. In 218 patients, hemostasis was achieved using the device (group I); 217 patients were assigned to the manual pressure control group (group II)., Results: There were no significant differences in baseline characteristics. Time to hemostasis was considerably shorter in group I (2.5 +/- 15.2 vs. 15.3 +/- 11.7 min [mean +/- SD], p < 0.0001). The deployment success rate for the device was 96%, and 76% of group I patients experienced immediate (within 1 min) hemostasis. Complication rates were lower in group I for bleeding, hematoma and occurrence of any complication. There was no difference in the small incidence of pseudoaneurysm formation. There was no change in either group in the ankle/brachial systolic blood pressure index. Ultrasound follow-up studies 60 days after device deployment revealed complete absorption of the device in all cases. Subgroup analysis revealed particular benefit in patients undergoing interventional procedures. The administration of heparin was associated with a significantly higher complication rate in the manual pressure control group, whereas heparin had no effect on hemostasis time or complication rates in the device group., Conclusions: This sheath-deployed, bioabsorbable device provides a safe and effective means of obtaining rapid arterial hemostasis after cardiac catheterization procedures. It appears to be particularly useful in those patients most at risk for access site complications.
- Published
- 1995
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23. Prolonged heparin therapy for occlusive intracoronary thrombus.
- Author
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Kolansky DM, Shapiro TA, and Laskey WK
- Subjects
- Coronary Angiography, Coronary Thrombosis diagnostic imaging, Humans, Male, Middle Aged, Coronary Thrombosis drug therapy, Heparin administration & dosage
- Abstract
The presence of intracoronary thrombus is associated with increased complications during coronary angioplasty. Such thrombus may also mimic the appearance of a critical stenosis. We report a case of nearly occlusive intracoronary thrombus which resolved after prolonged heparin therapy, revealing only a minimal underlying stenosis. The recognition and treatment of this entity is discussed.
- Published
- 1993
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24. Immediate postoperative management.
- Author
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Kolansky DM and Cohen LS
- Subjects
- Humans, Intraoperative Complications prevention & control, Postoperative Complications prevention & control, Heart Valve Diseases surgery, Postoperative Care
- Abstract
The management of the patient after valvular surgery is influenced by the preoperative left ventricular function and by the specific type of valvular lesion that has been corrected. The hemodynamics of the patient immediately after surgery must be evaluated carefully, and the patient can be supported with a variety of pharmacologic and mechanical measures as ventricular function recovers. Perioperative ischemia, arrhythmias, and bleeding may occur and should be specifically treated. Initiation of anticoagulation and adjustment of warfarin doses is an important aspect of postoperative care. Finally, the patient needs to be counseled that the presence of a prosthetic valve carries a risk for infective endocarditis and instructed on appropriate regimens for antibiotic prophylaxis.
- Published
- 1993
25. The A2 isoform of rat Na+,K(+)-adenosine triphosphatase is active and exhibits high ouabain affinity when expressed in transfected fibroblasts.
- Author
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Kolansky DM, Brines ML, Gilmore-Hebert M, and Benz EJ Jr
- Subjects
- 3T3 Cells, Animals, Blotting, Northern, Fibroblasts metabolism, Mice, RNA biosynthesis, Rats, Sodium-Potassium-Exchanging ATPase genetics, Ouabain metabolism, Sodium-Potassium-Exchanging ATPase metabolism, Transfection
- Abstract
The alpha isoforms of the Na+,K(+)-ATPase (Na+ pump) are expressed with developmental and tissue heterogeneity in rodents and possess different sensitivity to inhibition by ouabain. We directly characterized the ouabain sensitivity of the rat A2 (alpha 2) isoform by transfecting NIH 3T3 cells with rat A2. The treated cells exhibit high affinity (40 nM) ouabain binding with a density of 2 pmol/mg protein. 86Rb+ flux studies confirm that A2 is functional in this system and that A2 is inhibited by submicromolar concentrations of ouabain. These findings are consistent with measurements of ouabain affinity in tissues which express the A2 isoform.
- Published
- 1992
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26. Percutaneous transluminal coronary angioplasty in unstable and stable angina pectoris: a comparison of immediate success and complications.
- Author
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Ilia R, Kolansky D, Setaro J, Brennan J, Cabin H, Cleman M, and Remetz M
- Subjects
- Aged, Angina Pectoris mortality, Angina, Unstable mortality, Coronary Artery Bypass, Coronary Thrombosis mortality, Coronary Thrombosis therapy, Female, Humans, Male, Middle Aged, Myocardial Infarction mortality, Myocardial Infarction therapy, Recurrence, Survival Rate, Angina Pectoris therapy, Angina, Unstable therapy, Angioplasty, Balloon, Coronary
- Abstract
To determine the success rate and the safety of percutaneous transluminal coronary angioplasty in patients with unstable angina pectoris (group 1) versus stable angina (group 2), we studied 299 consecutive patients who underwent coronary angioplasty of 373 consecutive lesions. Of these patients, 149 had unstable angina pectoris and dilation of 188 arteries. The success rate was high and similar in both groups (95 and 93%, respectively). The groups did not differ in regard to the lesion characteristics, vessels and number of sites dilated except for an increase in the presence of thrombus in the unstable angina group (p < 0.03). Although there was a higher incidence of coronary thrombus and more acute myocardial infarction in group 1, the major complication rate did not differ from that of group 2 and was low in both of them (3 and 2%, respectively). No deaths occurred. Six patients (3 in each group) needed urgent coronary artery bypass grafting while 3 additional patients developed acute Q-wave myocardial infarction (all of them in group 1). Thus, percutaneous transluminal coronary angioplasty is a safe and successful procedure in patients with unstable angina as well as in patients with stable angina pectoris.
- Published
- 1992
- Full Text
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27. Pulmonary embolism presenting as exercise-induced hypotension.
- Author
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Sigal SL, Kolansky DM, Hughes S, Cabin HS, and Batsford WP
- Subjects
- Aged, Humans, Male, Pulmonary Artery diagnostic imaging, Pulmonary Embolism complications, Pulmonary Embolism diagnostic imaging, Radiography, Exercise Test, Hypotension etiology, Pulmonary Embolism diagnosis
- Abstract
A 68-year-old man with remote history of previous myocardial infarction presented with a four-week history of intermittent dyspnea. After developing hypotension during an exercise tolerance test, he underwent cardiac catheterization, revealing significant pulmonary hypertension and two-vessel coronary artery disease. Pulmonary angiography confirmed the presence of pulmonary emboli which partially resolved after thrombolytic therapy. Subsequent treadmill testing confirmed the absence of exercise-induced hypotension two months following treatment. This case underscores the importance of considering pulmonary embolism as a potential cause of exercise-induced hypotension, since it can be successfully treated with thrombolytic agents weeks after the initial onset of symptoms.
- Published
- 1991
- Full Text
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