Searched for: person:cheng04
Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail
Hansen, Johanna; Baum, Alina; Pascal, Kristen E; Russo, Vincenzo; Giordano, Stephanie; Wloga, Elzbieta; Fulton, Benjamin O; Yan, Ying; Koon, Katrina; Patel, Krunal; Chung, Kyung Min; Hermann, Aynur; Ullman, Erica; Cruz, Jonathan; Rafique, Ashique; Huang, Tammy; Fairhurst, Jeanette; Libertiny, Christen; Malbec, Marine; Lee, Wen-Yi; Welsh, Richard; Farr, Glen; Pennington, Seth; Deshpande, Dipali; Cheng, Jemmie; Watty, Anke; Bouffard, Pascal; Babb, Robert; Levenkova, Natasha; Chen, Calvin; Zhang, Bojie; Romero Hernandez, Annabel; Saotome, Kei; Zhou, Yi; Franklin, Matthew; Sivapalasingam, Sumathi; Lye, David Chien; Weston, Stuart; Logue, James; Haupt, Robert; Frieman, Matthew; Chen, Gang; Olson, William; Murphy, Andrew J; Stahl, Neil; Yancopoulos, George D; Kyratsous, Christos A
Neutralizing antibodies have become an important tool in treating infectious diseases. Recently, two separate approaches yielded successful antibody treatments for Ebola - one from genetically-humanized mice, and the other from a human survivor. Here, we describe parallel efforts using both humanized mice and convalescent patients to generate antibodies against the SARS-CoV-2 spike protein, yielding a large collection of fully-human antibodies that were characterized for binding, neutralization and three dimensional structure. Based on these criteria, we selected pairs of highly-potent individual antibodies that simultaneously bind the receptor-binding domain of the spike protein, providing ideal partners for a therapeutic antibody cocktail that aims to decrease the potential for virus escape mutants that might arise in response to selective pressure from a single antibody treatment.
PMID: 32540901
ISSN: 1095-9203
CID: 4484592
IASLC MULTIDISCIPLINARY RECOMMENDATIONS FOR PATHOLOGIC ASSESSMENT OF LUNG CANCER RESECTION SPECIMENS FOLLOWING NEOADJUVANT THERAPY
Travis, William D; Dacic, Sanja; Wistuba, Ignacio; Sholl, Lynette; Adusumilli, Prasad; Bubendorf, Lukas; Bunn, Paul; Cascone, Tina; Chaft, Jamie; Chen, Gang; Chou, Teh-Ying; Cooper, Wendy; Erasmus, Jeremy J; Ferreira, Carlos Gil; Goo, Jin-Mo; Heymach, John; Hirsch, Fred R; Horinouchi, Hidehito; Kerr, Keith; Kris, Mark; Jain, Deepali; Kim, Young Tae; Lopez-Rios, Fernando; Lu, Shun; Mitsudomi, Tetsuya; Moreira, Andre; Motoi, Noriko; Nicholson, Andrew G; Oliveira, Ricardo; Papotti, Mauro; Pastorino, Ugo; Paz-Ares, Luis; Pelosi, Giuseppe; Poleri, Claudia; Provencio, Mariano; Roden, Anja C; Scagliotti, Giorgio; Swisher, Stephen G; Thunnissen, Erik; Tsao, Ming Sound; Vansteenkiste, Johan; Weder, Walter; Yatabe, Yasushi
Currently there is no established guidance on how to process and evaluate resected lung cancer specimens following neoadjuvant therapy in the setting of clinical trials and clinical practice. There is also a lack of precise definitions on the degree of pathologic response, including major pathologic response (MPR) or complete pathologic response (CPR). In other cancers such as osteosarcoma, colorectal, breast and esophageal carcinomas, there have been multiple studies investigating pathologic assessment of the effects of neoadjuvant therapy including some detailed recommendations on how to handle these specimens. A comprehensive mapping approach to gross and histologic processing of osteosarcomas following induction therapy has been used for over 40 years. The purpose of this article is to outline detailed recommendations on how to process lung cancer resection specimens and to define pathologic response including MPR and CPR following neoadjuvant therapy. A standardized approach is recommended to assess the percentages of: 1) viable tumor, 2) necrosis and 3) stroma (including inflammation and fibrosis) with a total adding up to 100%. This is recommended for all systemic therapies including chemotherapy, chemoradiation, molecular targeted therapy, immunotherapy or any future novel therapies yet to be discovered whether administered alone or in combination. Specific issues may differ for certain therapies such as immunotherapy, but the grossing process should be similar and the histologic evaluation should contain these basic elements. Standard pathologic response assessment should allow for comparisons between different therapies and correlations with disease free survival and overall survival in ongoing and future trials. The International Association for the Study of Lung Cancer (IASLC) has an effort to collect such data from existing and future clinical trials. These recommendations are intended as guidance for clinical trials, although it is hoped they can be viewed as suggestion for good clinical practice outside of clinical trials, to improve consistency of pathologic assessment of treatment response.
PMID: 32004713
ISSN: 1556-1380
CID: 4294452
Management of Coronary Disease in Patients with Advanced Kidney Disease
Bangalore, Sripal; Maron, David J; O'Brien, Sean M; Fleg, Jerome L; Kretov, Evgeny I; Briguori, Carlo; Kaul, Upendra; Reynolds, Harmony R; Mazurek, Tomasz; Sidhu, Mandeep S; Berger, Jeffrey S; Mathew, Roy O; Bockeria, Olga; Broderick, Samuel; Pracon, Radoslaw; Herzog, Charles A; Huang, Zhen; Stone, Gregg W; Boden, William E; Newman, Jonathan D; Ali, Ziad A; Mark, Daniel B; Spertus, John A; Alexander, Karen P; Chaitman, Bernard R; Chertow, Glenn M; Hochman, Judith S; Abdallah, Abdallah M; Moreyra, Abel E; Laddu, Abhay A; Dubey, Abhishek; Goyal, Abhishek; Knighton, Abigail; Adeboye, Adedayo; Juceviciene, Agne; Urboniene, Agne; Szramowska, Agnieszka; Abdel-Latif, Ahmed; Ayoub, Ahmed; Elghamaz, Ahmed; Kamal, Ahmed; Talaat, Ahmed; Sharma, Ajay; Narula, Ajit Singh; Bagai, Akshay; Smigelskaite, Akvile; Raymond, Alain; Rheault, Alain; Loehr, Alaine Melanie; Varga, Albert; Maggioni, Aldo P; Moorman, Alec; Chevaile Ramos, Alejandro; Gisbert, Alejandro; Fratczak, Aleksandra; Laucevicius, Aleksandras; Chernyavskiy, Alexander M; Borisov, Alexander Sergeevich; Craft, Alexandra; Hunter, Alexandra; Hueb, Alexandre Ciappina; Schaan de Quadros, Alexandre; Muller, Alice Manica; Deiro, Aline Peixoto; Stone, Allegra; Castro, Almudena; Uxa, Amar; Van Craenenbroeck, Amaryllis; Roy, Ambuj; Kakkar, Amit; Flowers, Amy; Iskandrian, Amy; Djordjevic-Dikic, Ana D; Gomes Almeida, Ana; Francisco, Ana Rita; Mladenovic, Ana S; Santana, Ana; Lahiri, Anandaroop; Kuzmina-Krutetskaya, Anastasia M; Vamvakidou, Anastasia; Vertes, Andras; Gabriel, Andre; Bartykowszki, Andrea; Lorimer, Andrea; Pascual, Andrea; Coelho, Andreia; Rocha, Andreia; GarcÃa-Rincón, Andrés; Starovoytov, Andrew; Åabyk, Andrzej; Kawakami, Anelise; Hoye, Angela; Nobre, Angelo; Acharya, Anjali; Anand, Anjali; Rishmawi, Anjana; Banfield, Ann; Luyten, Ann; Cichocka-Radwan, Anna; Fojt, Anna; Plachcinska, Anna; Teresinska, Anna; Webb, Anne Marie; Heath, Anne; Mathew, Anoop; Vega, Antonia; Carvalho, Antonio; Colombo, Antonio; Fiarresga, Antonio; Tharini, Anu; Rao, Anupama; Valdespino-Estrada, Aquiles; Diaz, Ariel; Asif, Arif; Seto, Arnold H; Campos-Santaolalla, Arturo S; Cheema, Asim N; Ahmed, Asker; Mathur, Atul; Leong, Audrey W; Ã…kerblom, Axel; Fuentes, Axelle; Naher, Aynun; Valaiyapathi, Badhma; Srinivasan, Balaji; Kaur, Baljeet; Bhargava, Balram; Guruge, Bandula; Wicklund, Barbara; Czarniak, Bartosz; Singh, Bebek; Igual, Begoña; Merkely, Bela; Shah, Benoy N; de Bruyne, Bernard; Abramson, Beth; Stefanchik, Beth; Harvey, Bethany; Shivalkar, Bharati; Malik, Bilal; Kurian, Binoy Mannekkattukudy; Hammouche, Bougrida; Beleslin, Branko D; Ferguson, Bruce; McManus, Bruce; Ascoli, Bruna Maria; Smith, Bryn; Allen, Byron J; Gibson, C Michael; Bairey Merz, C Noel; Pop, Calin; Gagné, Carl-Éric; Ohmart, Carly; Kartje, Carol M; Alsweiler, Caroline; Rodgers, Caroline; Spindler, Caroline; Gruber, Carolyn J; Albert, Catherine; Bone, Catherine; Lemay, Catherine; Kepka, Cezary; Suvarna, Chandini; Mercure, Chantale; Wiyarand, Charlene; Patel, Chetan; Attanasio, Chiara; Chow, Chi-Ming; Er, Ching Min; Ong, Ching-Ching; Manjunath, Cholenahally Nanjappa; Buller, Chris; Vassaliere, Christel; Vrints, Christiaan; Witzke, Christian; Ballantyne, Christie; Björklund, Christina; Roraff, Christine; Laure, Christophe; Thuaire, Christophe; Chan, Christopher; Fordyce, Christopher; Kinsey, Christopher; Xia, Chunli; Schultz, Cidney; Held, Claes; Cortés, Claudia; Escobar, Claudia; Freixo, Cláudia; Kadalie, Clemens T; Thobois, Corine; Page, Courtney; Bare, Cristina; Espinosa, Dalisa; Gao, Dan; Rizk, Dana; Puzhevsky, Daniela; Analyst, Data; Charytan, David M; Williams, David O; Booth, David; Charytan, David; Cohen, David; DeMets, David; Foo, David; Goldfarb, David; Schlichting, David; Sisson, David; Taggart, David; Waters, David; Wheeler, David; Williams, David; Vo, Davis; Teodorczyk, Dawid; Shelstad, Dawn D; Kereiakes, Dean; Yip, Deborah; Ramaswamy, Deepa; Mattina, Deirdre; Murphy, Deirdre; Jiang, Dengke; Cyr, Derek; Cukali, Diana; Camara, Diane; Stournaras, Dimitrios; Patel, Dipti; Li, Dongze; Exley, Donna; Reimann, Doreen; Schwartz, Doron; Cacela, Duarte; Conway, Dwayne S G; Punnoose, Eapen; Tay, Edgar L; Karanjah, Edgar; Gomes Lima, Eduardo; Hernandez-Rangel, Eduardo; Nicol, Edward D; Kaczmarska, Edyta; Refoyo Salicio, Elena; Feen, Eli; Durán-Cortés, Elihú; Janzen, Elisabeth M; van Dongen, Elise; Restelli Piloto, Elissa; Srbinovska Kostovska, Elizabeta; Capasso-Gulve, Elizabeth; Zbyshevskaya, Elizaveta V; Fridell, Ellie; Lader, Ellis W; Gosmanova, Elvira; Tachot, Emilie; Howard, Emma; Sorbets, Emmanuel; Alonso-Ãlvarez, Encarnación; Daugas, Eric; Alexánderson Rosas, Erick; Montpetit, Estelle; Passamani, Eugene; Shutov, Evgeny; Szczerba, Ewa; Wojtala, Ewelina; Ribeiro Silva, Expedito Eustáquio; Fimiani, Fabio; Hage, Fadi; Jafary, Fahim Haider; Feng, Fang; Ranjbaran, Fatima; Pinto, Fausto J; Caeiro, Fernando; Nolasco, Fernando; Silva, Filipa; Ottani, Filippo; Al Solaiman, Firas; Egydio, Flávia; Chereches, Florina; De Micco, Francesca; Bianchini, Francesca; Pietrucci, Francesca; Orso, Francesco; Pisano, Francesco; Patuleia Figueiras, Francisca; Madore, François; Harrell, Frank; Rockhold, Frank; Van de Werf, Frans; Guenther, Franziska; Mohr, Fred; Karthikeyan, G; Galeote, Gabriel; Grossmann, Gabriel; Steg, Gabriel; Guzman, Gabriela; Gabrielli, Gabriele; Chen, Gang; Sharma, Gautam; Petty, Gaylin; Mikolaitiene, Gelmina; Yee, Gennie; Devlin, Gerard Patrick; Esposito, Gerard; Ãgoston, Gergely; Lamas, Gervasio; Cobb, Gia; Perna, Gian Piero; Leone, Gianpiero; Mishra, Girish; Barge-Caballero, Gonzalo; Young, Grace M; Scaro, Graciela; Wong, Graham; Pressman, Gregg; Simonis, Gregor; Steinmaurer, Gudrun; Portugal, Guilherme; Cantinho Lopes, Guilhermina; Garcia-Garcia, Guillermo; Wang, Guoqin; Wander, Gurpreet S; Gulati, Gurpreet; Zhang, Haibo; Marciniak, Halina; Dai, Hao; Dong, Haojian; Franch, Harold; White, Harvey; Elabd, Hatem; Pomeroy, Hayley; Golden, Heather; Wilson, Heidi; Abergel, Helene; Siddaram, Hemalata; Mahapatra, Hemant Shakhar; Stokes, Henry C; Osseni, Hermine; Schuchlenz, Herwig; Skali, Hicham; Mattix-Kramer, Holly; Cheng, Hong; Mahrous, Hossam; Pejkov, Hristo; Marques, Hugo; Zhong, Hui; El Fishawy, Hussien; Webb, Ian; Kullo, Iftikhar; Grazhdankin, Igor O; Hassan, Ikraam; Pina, Ileana L; Tamasauskiene, Ilona; Cabrita, Inês Zimbarra; Rodrigues, Ines; Soveri, Inga; Mitevska, Irena Peovska; Lang, Irene Marthe; Subbotina, Irina; Kalibataite-Rutkauskiene, Irma; Roy, Isabelle; Tejani, Ishita; Naryshkin, Ivan A; Jankovic, Ivana; Niedzwiecka, Iwona; Kusmierek, Jacek; Chow, Jackie; Heo, Jaekyeong; Maksym, Jakub; Davies, James E; Jang, James J; Hirsch, James; Tatoulis, James; Henzel, Jan; Oliveira, Janaina; Rangaswami, Janani; Eckstein, Jane; Raj, Janitha; Pozzibon, Jaqueline; Drozdz, Jaroslaw; Kwok Kong, Jason Loh; Call, Jason T; Linefsky, Jason; Garcia, Javier J; Meisner, Jay; Scales, Jayne; Juliard, Jean Michel; Diodati, Jean; Juliard, Jean-Michel; Russo, Jeanne; Schoep, Jeannette J M; Leimberger, Jeff; Milliken, Jeffrey C; Anderson, Jeffrey; Kanters, Jeffrey; Lorin, Jeffrey; Moses, Jeffrey; Stepanovic, Jelena J; Celutkiene, Jelena; Stojkovic, Jelena; Jose, Jenne M; Stanford, Jennifer L; Hogan, Jennifer; Horst, Jennifer; Isaacs, Jennifer; Thomson, Jennifer; Tomfohr, Jennifer; White, Jennifer; Yee, Jerry; Berg, Jessica; Peteiro, Jesus; Peteiro, Jesús; Li, Jia; Liu, Jiamin; Zhang, Jianxin; Marcus, Jill; Blankenship, Jim; Dong, Jing; Chen, Jiyan; Evans, Jo; Peñafiel, JoaquÃn V; Sabik, Joe; Christopher, Johann; Kostis, John B; Graham, John Joseph; Doan, John; Jose, John; Kotter, John; Lehman, John; Middleton, John; Pownall, John; Gleadle, Jonathan M; Chavez-Iñiguez, Jonathan S; Byrne, Jonathan; Himmelfarb, Jonathan; Lebowitz, Jonathan; Thorsen, Jonean; Carrillo Calvillo, Jorge; Escobedo, Jorge; Ortega-RamÃrez, José A; Cuenca-Castillo, José J; Diez, Jose L; Narro Villanueva, José Luis; da Costa Vieira, José Luiz; Flores-Palacios, José M; Fragata, Jose; Lopes, Jose; Lopez-Sendon, Jose; Lopez-Sendon, José; Rueda, Jose; Selvanayagam, Joseph B; Sacco, Joseph; Loh, Joshua P; Burkhardt, Joy; López Quijano, Juan Manuel; Gaztanaga, Juan; Sebo, Judit; Wright, Judith; Stumpf, Juergen; de Aveiro Morata, Julia; Figal, Julio César; Hernandez Jaras, Julio; Yang, Junqing; Garg, Jyotsna; Rani, K Manjula; Preethi, K; Goetschalckx, Kaatje; Calfas, Karen; Petrosyan, Karen; Servilla, Karen; Swan, Karen; Ploetze, Karin; Kryczka, Karolina; Wojtczak-Soska, Karolina; Wojtera, Karolina; Ramasamy, Karthik; Åuczak, Katarzyna; Malinowska, Katarzyna; Knaut, Katharina; Martin, Katherine; Claes, Kathleen; Mason, Kathryn; Mahaffey, Ken; Gin, Kenneth; Lee, Kerry; Bonin, Kerstin; Mikes, Kerstin; Bainey, Kevin R; Harley, Kevin T; Marzo, Kevin; McMahon, Kevin; Abdul-Nour, Khaled; Alfakih, Khaled; Dajani, Khaled; Kushniriuk, Khrystyna; Poh, Kian-Keong; Holland, Kim; Halverson, Kimberly E; Murphy, Kinnari; Reddy, Kiran; Quiles, Kirsten J; Abercrombie, Kirsty; Matschke, Klaus; Szymczyk, Konrad; Chan, Koo Hui; Mavromatis, Kreton; Hongalgi, Krishnakumar; Thygesen, Kristian; Salmi, Kristin M; Newby, Kristin; Arges, Kristine; Teoh, Kristine; Drzymalski, Krzysztof; Kumbar, Lalathaksha; Matics, Laszlone; Hickson, LaTonya J; Keinaite, Laura; Sarti, Laura; True, Laura; Phillips, Lawrence M; Friedman, Lawrence; Maranan, Leandro C; Lotaif, Leda; Dharmarajan, Lekshmi; Bockeria, Leo A; Pizzol Caetano, Leonardo; Bridi, Leonardo; Bershtein, Leonid L; Yan, Li Hai; Li, Li; Sousa, Lidia; Xu, Lihong; Zhang, Lihua; Zhang, Lili; Mazza Barbosa, Lilian; Tozija, Liljana; Arcand, Linda; Patricio, Lino; Zhang, Liping; Hatch, Lisa; Jiang, Lixin; Low, Liz; Salman, Loay; Lopez, Lorena; Pritchard, Lori; Bernanrdes, Luis; Guzman, Luis; Teo, Lynette L; Reddy, M Sowjanya; Simoons, Maarten; Konigstein, Maayan; Selas, Mafalda; Madero, Magdalena; Miller, Magdalena; Misztal-Teodorczyk, Magdalena; Abdelhamid, Magdy; Fahim, Magid; Mylarappa, Mahevamma; Joseph, Majo X; Frach, Malgorzata; Rani, Manjula; Galvani, Marcello; Demkow, Marcin; Szkopiak, Marcin; De Fabritis, Marco; Magnoni, Marco; Marini, Marco; Sicuro, Marco; Roik, Marek; Alfonso, Maria A; Pereira de Moraes, Maria Antonieta; MartÃnez-RuÃz, MarÃa Dolores; Canziani, Maria Eugenia; Martin, Maria Eugenia; Caetano, Maria Inês; Corral, Maria P; Pérez GarcÃa, Maria; Andreasson, Maria; Posada, Maria; Dracoulakis, Marianna D A; Rubio, Mariano; Petrovic, Marija T; Vieira, Marina; Garcia, Mario J; D'arezzo, Mario; Orgera, Maris; Miglinas, Marius; Garand, Mark; Peterson, Mark; Xavier, Mark; Mosley, Marlowe; Capinha, Marta; Swiderek, Marta; Meyer, Martha; Ceseri, Martina; Tricoli, Martinia; Wiilliams, Mary; Champagne, Mary Ann; Streif, Mary; Leesar, Massoud; Claudia, Matei; Solecki, Mateusz; Mungo, MatÃas Nicolás; Shinseki, Matthew; Weir, Matthew; Nédio, Maura Carina; Winter, Max-Paul; Krishnam, Mayil S; Mishra, Meenakshi; Hwang, Mei; Srilatha, Melemadathil; LeFevre, Melissa; Simegn, Mengistu; Gibson, Michael A; Rubens, Michael B; Shapiro, Michael D; Chobanian, Michael; Davidson, Michael; Farkouh, Michael; Mack, Michael; Wlodarczyk, Michal; Khouri, Michel G; Crowder, Michelle; Ratliff, Michelle; Borges Santos, Miguel; Nobre Menezes, Miguel; Perez Fontan, Miguel; Barrero, Miguel; Tapolyai, Mihaly; Torosoff, Mikhail T; Dobric, Milan R; Gadkari, Milind Avdhoot; Kyaw, Min Tun; Revivo, Miri; Lustre, Mitchel B; Adel, Mohamed; Hassan, Mohamed; El-Hajjar, Mohammad; Hussain, Mohammed; Saleem, Mohammed; Blanco-Calvo, Moisés; Jiménez-Santos, Moisés; Laukyte, Monika; Saric, Muhamed; Takiuti, Myrthes Emy; Asif, Nadia; Moorthy, Nagaraja; Ogletree, Naima L; Katamadze, Nana O; Nataraj, Nandita; Uchida, Naomi; Ismail, Nasrul; Oliveira, Natalia S; de Carvalho Maffei, Natalia; Brosens, Nathalie; Aslam, Naved; Akhtar, Naveed; Mowafy, Neamat; Pandit, Neeraj; Parakh, Neeraj; Pannu, Neesh; Duncan, Neill; Garcevic, Nevena; Meadows, Ngaire; Danchin, Nicholas; Deming, Nicole; Boskovic, Nikola N; Karogiannis, Nikolaos; Zhang, Ning; Kumar, Nirmal; Sharma, Niruta; Chadha, Nitika; Naik, Nitish; Durfee, Noelle M; Cosgrove, Nora M; Urbanski, Norbert; Hogg, Norma; Walesiak, Olga; ZdoÅ„czyk, Olga; Zhdanova, Olga; Anaya, Olivia; Bello, Olugbenga; Almousalli, Omar; Thompson, Omar; Kliuk, Orit; Méndiz, Oscar; Prada-Delgado, Óscar; Shapira, Oz; Raffaele, Pablo; Salanger, Page; Maurovich-Horvat, Pal; Garg, Pallav; Moraga, Paloma; Singh, Pam; Ouyang, Pamela; Woodard, Pamela; Poggio Smanio, Paola Emanuela; Smanio, Paola; Calabro, Paolo; Nguyen, Patricia K; Alarie, Patricia; Carrilho, Patricia; Endsley, Patricia; Pellikka, Patricia; Lebioda, Patrycja; Der Mesropian, Paul; Hauptman, Paul; GarcÃa-González, Paula; Wilson, Paula; Cury Rezende, Paulo; Novis Rocha, Paulo; Canas Silva, Pedro; Farto E Abreu, Pedro; PÃccaro de Oliveira, Pedro; Carvalho, Pedro; Modas, Pedro; Rio, Pedro; He, Peiyu; McCullough, Peter A; Stone, Peter H; Douglass, Peter; Sizeland, Peter; Voros, Peter; Steg, Philippe Gabriel; Genereux, Philippe; Généreux, Philippe; Menasche, Philippe; Rheault, Philippe; Tassinario, Piero; Gervais, Pierre; Calvillo, Pilar; Chai, Ping; Jakubowski, Piotr; Pruszczyk, Piotr; Loh, Poay-Huan; Samadi, Pouneh; Deedwania, Prakash; Patel, Pranav M; Polamuri, Praneeth; Sharma, Pratiksha; Kamath, Preeti; Thomas, Prince; Arambam, Priyadarshani; Sodhi, Puneet; Naik, Pushpa; Zhong, Qi; Zhao, Qian; Yuan, Qianqian; Xie, Qiulan; Murphy, Rachel; Lyubarova, Radmila; Lyubarova, Radmilar; Fisher, Raewyn; Diaz, Rafael; Maldonado, Rafael; Selgas, Rafael; Bugiardini, Raffaele; Chaudhry, Rafia; Kavalakkat, Raisa; Vs, Rajalekshmi; Nair, Rajesh Gopalan; Narang, Rajiv; Yadav, Rakesh; Carvalho, Ramiro; Jesús-Pérez, Ramon de; Leng, Ran; Kachru, Ranjan; Sanchez, Raquel; Dwyer, Raven R; Lee, Raven; Wyman, Ray; Wong, Raymond C; Hampson, Reinette; Karam Kalil, Renato Abdala; Lopes, Renato D; Eick, Renato George; Lopes, Renato; Ravindran, Reshma; Gamma, Reto Andreas; Costa, Ricardo; Bhatt, Richa; Trimlett, Richard H J; Patel, Risha; Coram, Rita; Riezebos, Robert K; Donnino, Robert M; Guyton, Robert; Harrington, Robert; Malecki, Robert; Favaloro, Roberto René; Elliott, Robyn; Lima, Rodolfo G S D; Tandon, Rohit; Doerr, Rolf; Tewari, Roma; Wald, Ron; Hu, Rongrong; Collins, Rory; Mehran, Roxana; Senior, Roxy; Baleón-Espinosa, Rubén; Ramos, Ruben; Ferreira, Rui; Kirby, Ruth; Pérez-Fernández, Ruth; Ramakrishnan, S; Dwivedi, S K; Lubna, Sadath; Ahmed, Sadiq; Govindan, Sajeev Chakanalil; Alfalahi, Salamah; Cruz-Flores, Salvador; Costa, Salvatore P; Setty, Sampoornima; Nwosu, Samuel; Mahajan, Sandeep; Seth, Sandeep; Singh, Sandeep; Niehe, Sander R; Carr, Sandy; Ogrizovic, Sanja Simic; Ogrizovic, Sanja; Gulati, Sanjeev; Sharma, Sanjeev; Fernandez, Sara; Williams, Sarah; Ralhan, Sarju; Kedev, Sasko; Singh, Satinder; Sankaranarayanan, Satish; Manjunath, Satvic Cholenahally; Lee, Sau; Thaxton, Schawana; O'Brien, Sean M; Sobczak, Sebastian; Nour, Seema; Sayganov, Sergey A; Bravo Baptista, Sérgio; Draibe, Sergio; Sokol, Seth; Chandra, Sharad; Mackedanz, Shari; Goodman, Shaun; Shirazian, Shayan; Karwa, Sheetal Rupesh; Ussery, Sheri; Bajaj, Sheromani; Heydari, Shirin; Choudhary, Shiv Kumar; Patel, Shivali; Pandey, Shruti; Zhang, Shuyang; Gadage, Siddharth; Tan, Sik-Yin V; Poletti, SÃlvia Zottis; Valbuena, Silvia; Savaris, Simone; Yakubov, Solomon; Zhu, Songlin; Gupta, Sonika; Brener, Sorin; Gurunathan, Sothinathan; Nayak, Soundarya; Reddy, Sowjanya; Cobos, Stanley E; Weikl, Stefan; Lane, Stephanie M; Ferket, Stephanie; Mavromichalis, Stephanie; Fremes, Stephen; Fein, Steven A; Sedlis, Steven P; Giovannone, Steven; Weitz, Steven; Banerjee, Subhash; Hegde, Sudhanva S; Hosino, Suellen; Mookherjee, Sulagna; Singh, Suman; Abeygunasekara, Sumith; Mishra, Sundeep; Verma, Sunil Kumar; Kumar, Suresh; Narayanappa, Suryaprakash; Milbrandt, Susan K; Silva, Susana; Stevens, Susanna; Kolhe, Suvarna; Tavares, Suzana; Welsh, Suzanne; Kishore, T A; Colaiácovo Soares, Tamara; Pillay, Tapan Umesh; Rashid, Tarek; Mittal, Tarun K; Duarte, Tauane Bello; Dutoiu, Téodora; Delgadillo, Teresa; Chua, Terrance; Welch, Terrance; Kofidis, Theodoros; Lefevre, Thierry; Silva, Tiago; Boros, Timea; Lau, Titus; Formisano, Tiziana; Ciurus, Tomasz; Tarchalski, Tomasz; Tan, Tracy; Lingaraj, Umesh; Bahl, V K; Narain, V S; Pellu, Valentina; Lobo, Valentine; Robesyn, Valerie; Yadav, Vandana; Gupta, Veerabhadra; Mathew, Verghese; Miro, Vicente; Gumerova, Victoria; Hernandez, Victoria; Kher, Vijay; Kumar, Vijay; Makkar, Vikas; Reddy, Vikranth; Bulkley, Viktoria; David, Vinoi George; Misra, Virendra; Fernández-Figares, Virginia; Ryasniansky, Vladimir; Giga, Vojislav L; Almahmeed, Wael A; Chan, Wan Xian; Marfori, Wanda C; Parker, Wanda; Pennachi, Wayne; Lau, Wei Ling; Xing, Weibing; Bian, Weijing; Stewart, Wendy L; Drewes, Wendy; Hueb, Whady; Weintraub, William; Sia, Winnie C; Flores-RÃos, Xacobe; Ma, Xiang; Gu, Xiangqiong; Li, Xiaomei; Xu, Xiaoyi; Fu, Xin; Li, Xuemei; Wang, Xutong; Pépin-Dubois, Yanek; Arbel, Yaron; Han, Yechen; Lit, Yiming; Sia, Ying Tung; Wang, Ying; Yang, Yining; Ma, Yitong; Peralta, Yolayfi; Smets, Yves; Taul, Yvonne; Kudzoeva, Zalina; Markovic, Zeljko Z; Liu, Zhangsuo; Liu, Zhenyu; Ye, Zhiming; Yu, Zixiang; Davidovits, Zoltan; Petronijevic, Zvezdana
BACKGROUND:Clinical trials that have assessed the effect of revascularization in patients with stable coronary disease have routinely excluded those with advanced chronic kidney disease. METHODS:We randomly assigned 777 patients with advanced kidney disease and moderate or severe ischemia on stress testing to be treated with an initial invasive strategy consisting of coronary angiography and revascularization (if appropriate) added to medical therapy or an initial conservative strategy consisting of medical therapy alone and angiography reserved for those in whom medical therapy had failed. The primary outcome was a composite of death or nonfatal myocardial infarction. A key secondary outcome was a composite of death, nonfatal myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. RESULTS:At a median follow-up of 2.2 years, a primary outcome event had occurred in 123 patients in the invasive-strategy group and in 129 patients in the conservative-strategy group (estimated 3-year event rate, 36.4% vs. 36.7%; adjusted hazard ratio, 1.01; 95% confidence interval [CI], 0.79 to 1.29; P = 0.95). Results for the key secondary outcome were similar (38.5% vs. 39.7%; hazard ratio, 1.01; 95% CI, 0.79 to 1.29). The invasive strategy was associated with a higher incidence of stroke than the conservative strategy (hazard ratio, 3.76; 95% CI, 1.52 to 9.32; P = 0.004) and with a higher incidence of death or initiation of dialysis (hazard ratio, 1.48; 95% CI, 1.04 to 2.11; P = 0.03). CONCLUSIONS:Among patients with stable coronary disease, advanced chronic kidney disease, and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of death or nonfatal myocardial infarction. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA-CKD ClinicalTrials.gov number, NCT01985360.).
PMID: 32227756
ISSN: 1533-4406
CID: 5451232
Initial Invasive or Conservative Strategy for Stable Coronary Disease
Maron, David J; Hochman, Judith S; Reynolds, Harmony R; Bangalore, Sripal; O'Brien, Sean M; Boden, William E; Chaitman, Bernard R; Senior, Roxy; López-Sendón, Jose; Alexander, Karen P; Lopes, Renato D; Shaw, Leslee J; Berger, Jeffrey S; Newman, Jonathan D; Sidhu, Mandeep S; Goodman, Shaun G; Ruzyllo, Witold; Gosselin, Gilbert; Maggioni, Aldo P; White, Harvey D; Bhargava, Balram; Min, James K; Mancini, G B John; Berman, Daniel S; Picard, Michael H; Kwong, Raymond Y; Ali, Ziad A; Mark, Daniel B; Spertus, John A; Krishnan, Mangalath N; Elghamaz, Ahmed; Moorthy, Nagaraja; Hueb, Whady A; Demkow, Marcin; Mavromatis, Kreton; Bockeria, Olga; Peteiro, Jesus; Miller, Todd D; Szwed, Hanna; Doerr, Rolf; Keltai, Matyas; Selvanayagam, Joseph B; Steg, P Gabriel; Held, Claes; Kohsaka, Shun; Mavromichalis, Stavroula; Kirby, Ruth; Jeffries, Neal O; Harrell, Frank E; Rockhold, Frank W; Broderick, Samuel; Ferguson, T Bruce; Williams, David O; Harrington, Robert A; Stone, Gregg W; Rosenberg, Yves; Ricci, Joseph; Tello Montoliu, A; Robero Aniorte, A I; Mulder, Abbey; Laddu, Abhay A; Goyal, Abhinav; Dubey, Abhishek; Goyal, Abhishek; Knighton, Abigail; Oomman, Abraham; Jaskowiak, Adam J; Kolodziej, Adam; Witkowski, Adam; Hameed, Adnan; Anesini, Adriana; Hussain, Afshan; Juceviciene, Agne; Urboniene, Agne; Jakal, Agnes; Szramowska, Agnieszka; Khairuddin, Ahmad; Abdel-Latif, Ahmed; Adel, Ahmed; Aljzeeri, Ahmed; Kamal, Ahmed; Talaat, Ahmed; Mann, Aimee; Contreras, Aira; Kumar, Ajit; Kumar, V K; Furukawa, Akemi; Bagai, Akshay; Smigelskaite, Akvile; Furber, Alain; Rheault, Alain; Loehr, Alaine Melanie; Rosen, Alan; Varga, Albert; Qelaj, Albertina; Barioli, Alberto; Russo, Aldo; Moorman, Alec; Gisbert, Alejandro; Fratczak, Aleksandra; Laucevicius, Aleksandras; Kuleshova, Alena; Sionis, Alessandro; Sirker, Alexander A; Chernyavskiy, Alexander M; Craft, Alexandra; Vazquez, Alexandra; Ciappina Hueb, Alexandre; Colafranseschi, Alexandre S; Schaan de Quadros, Alexandre; Tognon, Alexandre; Alghamdi, Ali; Manica Muller, Alice; 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Ireland, Kim F; Holland, Kim; Byrne, Kimberly Ann; Halverson, Kimberly E; Elmore, Kimberly; Miller-Cox, Kimberly; Reddy, Kiran; Quiles, Kirsten J; Abercrombie, Kirsty; Matschke, Klaus; Szymczyk, Konrad; Chan, Koo Hui; Preethi, Kotiboinna; Sokhon, Kozhaya; Meemuk, Krissada; Thygesen, Kristian; Salmi, Kristin M; Newby, Kristin; Wippler, Kristina; Arges, Kristine; Teoh, Kristine; Etherington, Krystal; Åoboz-GrudzieÅ„, Krystyna; Reczuch, Krzysztof W; Bury, Krzysztof; Drzymalski, Krzysztof; KukuÅ‚a, Krzysztof; Sung, Kuo-Tzu; Huber, Kurt; Douangvila, Ladda; Sullenberger, Lance; Trama, Larissa Miranda; Matics, Laszlone; Drew, Laura; Flint, Laura; Keinaite, Laura; Sarti, Laura; Kolakaluri, Laurel; Phillips, Lawrence M; Friedman, Lawrence; Phillips, Lawrence; Velicki, Lazar; Howell, Leah; Maranan, Leandro C; Cox, Leanne; Daba, Ledjalem; Zhang, Lei; Dharmarajan, Lekshmi; Bockeria, Leo; Pizzol Caetano, Leonardo; Bridi, Leonardo; Bershtein, Leonid L; Sokalski, Leszek; Yan, Li Hai; Li, Li; Nijmeijer, Lia; 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Vila Perales, Montserrat; Al-Mallah, Mouaz H; de Oliveira Filho, Moysés; Ntsekhe, Mpiko; Saric, Muhamed; Chen, Mulei; Brousseau, Myriam; Takiuti, Myrthes Emy; Cemerlic-Adjic, Nada; Asif, Nadia; Gakou, Nadia; Hussain, Nafisa; Katamadze, Nana O; Clapp, Nancy L; Aedy, Nancy; Nataraj, Nandita; Wenger, Nanette K; Uchida, Naomi; Ismail, Nasrul; Oliveira, Natalia S; de Carvalho Maffei, Natalia; Spitzer, Natalie; Putnam, Natasha C; Aslam, Naved; Mowafy, Neamat; Pandit, Neeraj; Parakh, Neeraj; Garcevic, Nevena; Meadows, Ngaire; Tran, Nhi N; Danchin, Nicholas; Lakeman, Nicki; Johnston, Nicola; Shammas, Nicolas W; Saint Vrestil, Nicole; Deming, Nicole; Zhong, Nier; Patel, Niket; Boskovic, Nikola N; Karogiannis, Nikolaos; Werner, Nikos; Johnston, Nina; Zhang, Ning; Zhou, Ning; Hindoyan, Niree; Kumar, Nirmal; Chadha, Nitika; Naik, Nitish; Aripova, Nodira; Mtana, Noloyiso; Eskelson, Nona A; Mokhtar, Noor Syamira; Taksaudom, Noppon; Basri, Nor Asiah; Marchelletta, Nora; Hogg, Norma; Jungla, Nungshi; Ferreira, Nuno; Lubyanaya, Oksana A; Nikolaeva, Olga B; Cañavate, Olga; Sobrino, Olga; Walesiak, Olga; Walter, Olga; ZdoÅ„czyk, Olga; Lim, Olivia J; Anaya, Olivia; Mancilla, Olivia; Dubourg, Olivier; Bello, Olugbenga; Almousalli, Omar; Thompson, Omar; Olurinde, Oni; Harel, Or; Raheem, Osama; Méndiz, Oscar; Prada-Delgado, Óscar; Shapira, Oz; Schulze, P Christian; Panpunuan, Pachara; Maurovich-Horvat, Pal; Garg, Pallav; Moraga, Paloma; Singh, Pam; Julian, Pamela; Ouyang, Pamela; Sigel, Pamela; Woodard, Pamela; Zhou, Panpan; Poggio, Paola Emanuela; Smanio, Paola; Calabro, Paolo; Jeetley, Paramjit; Goube, Pascal; Nguyen, Patricia K; Alarie, Patricia; Arakelian, Patricia; Arsenault, Patricia; Blaise, Patricia; Brito, Patricia; Cowper, Patricia; Endsley, Patricia; Mieses, Patricia; Alexander, Patrick B; Donnelly, Patrick; Wilmot, Patrick; Lebioda, Patrycja; Gordon, Paul C; Mesropian, Paul Der; Galiwango, Paul; Hauptman, Paul; Kennedy, Paul; Beardsley, Paula; GarcÃa-González, Paula; Rezende, Paulo Cury; Caramori, Paulo Ricardo; Kozlov, Pavel S; Canas Silva, Pedro; Melo Barros E Silva, Pedro Gabriel; PÃccaro de Oliveira, Pedro; Carvalho, Pedro; Modas, Pedro; Rio, Pedro; Jain, Peeyush; He, Peiyu; McCullough, Peter A; Stone, Peter H; Pollak, Peter M; Douglass, Peter; Henriksen, Peter; OKane, Peter; Ong, Peter; Jones, Philip; Rogal, Philip; Généreux, Philippe; Menasche, Philippe; Rheault, Philippe; Goold, Phoebe; Gervais, Pierre; Michaud, Pierre; Calvillo, Pilar; Chai, Ping; Jakubowski, Piotr; Pruszczyk, Piotr; Slomka, Piotr; Sritara, Piyamitr; Loh, Poay-Huan; Sonawane, Poonam; Samadi, Pouneh; Parikh, Pragnesh P; Deedwania, Prakash; Patel, Pranav M; Polamuri, Praneeth; Sharma, Pratiksha; Vasquez, Precilia; Kamath, Preeti; Thomas, Prince; Arambam, Priyadarshani; Mehta, Puja K; Grant, Purvez; Naik, Pushpa; Zhong, Qi; Zhao, Qian; Zhou, Qiang; Yuan, Qianqian; Yu, Qin; Li, Qingxian; Xie, Qiulan; Zeng, Qiutang; Vindhya, R J; Gerlach, R James; King, Rachel; VuÄić, Rada; Lyubarova, Radmila; Pracon, Radoslaw; Fisher, Raewyn; Beyar, Rafael; Diaz, Rafael; Selgas, Rafael; Bugiardini, Raffaele; Fanelli, Raffaele; Kavalakkat, Raisa; Rajalekshmi, V S; Barua, Rajat S; Menon, Rajeev; Nair, Rajesh Gopalan; Francis, Rajesh; Narang, Rajiv; Yadav, Rakesh; Huston, Ralph Alan; Ramakrishnan, T; de Silva, Ramesh; Mahmoud, Rami El; Carvalho, Ramiro; de Jesús-Pérez, Ramon; Stevens, Ramona; Leng, Ran; Kachru, Ranjan; Nath, Ranjit Kumar; Sanchez, Raquel; Dwyer, Raven R; Lee, Raven; Wyman, Ray; Wong, Raymond C; Little, Raymond W; Ocaranza Sanchez, Raymundo; Wimmer, Rebecca J; Bariciano, Rebecca; Otis, Rebecca; Herrmann, Rebekah R; Yunis, Reem; Hampson, Reinette; Karam, Renato Abdala; Hessian, Renee C; Kaneshiro, Renee; Ravindran, Reshma; Gamma, Reto Andreas; Bhandari, Reyna; Arsanjani, Reza; Lopes, Ricardo L; Mendes Oliveira, Ricardo; Costa, Ricardo; Bhatt, Richa; Davies, Richard F; Trimlett, Richard H J; Goldweit, Richard; Hermanides, Rik; Nakanishi, Rine; Sidh, Rinu R; Patel, Risha; Coram, Rita; Siddiqui, Rizwan A; Beanlands, Rob S; Hamburger, Robert J; Riezebos, Robert K; Donnino, Robert M; Bojar, Robert; Chilton, Robert; Guyton, Robert; Henderson, Robert; Kornberg, Robert; Leber, Robert; Mao, Robert; Stenberg, Robert; Santos, Roberta P; Favaloro, Roberto René; Amati, Roberto; Lima, Rodolfo G S D; Cerci, Rodrigo J; Tumelero, Rogerio; Tandon, Rohit; Tewari, Roma; Miranda-Peats, Romalisa; Wald, Ron; Mastouri, Ronald A; Morford, Ronald G; Schwartz, Ronald G; Pedalino, Ronald P; Hu, Rongrong; Hansen, Ronnell A; Cohen, Ronny A; Hachamovitch, Rory; Homem, Rosa; Sandonato, Rosa; Laimer, Rosane; Gans, Rosann; Yost, Roxanne; Mathew, Roy; Baleón-Espinosa, Rubén; Ramos, Ruben; Gevorgyan, Rubine; Ferreira, Rui; Jing, Rui; Pérez-Fernández, Ruth; Dwivedi, S K; Ramakrishnan, S; Khan, Saadat; Bokhari, Sabahat; Thomas, Sabu; Lubna, Sadath; Khan, Sajeeda Parveen; Govindan, Sajeev Chakanalil; Girotra, Saket; Kassam, Saleem; Canada, Sallie; Cruz-Flores, Salvador; Mohamed, Samaa; Ly, Samantha; El Kaffas, Sameh; Massalha, Samia; Setty, Sampoornima; Nwosu, Samuel; Seth, Sandeep; Singh, Sandeep; Niehe, Sander R; Rivest, Sandra M; Zier, Sandra S; Ahoud, Sandra; Carr, Sandy; Ganapathi, Sanjay; Shetty, Sanjay; Sharma, Sanjeev; Jimenez, Santa; Satheesh, Santhosh; Garcia, Santiago A; Fernandez, Sara; Karlsson, Sara; Salkind, Sara; Temiyasathit, Sara; Medina Rodriguez, Sarah; Beaudry, Sarah; Hadjih, Sarah; Williams, Sarah; Zahrani, Sarah; Ralhan, Sarju; Hinic, Sasa; Kedev, Sasko; Singh, Satinder; Yasuda, Satoshi; Manjunath, Satvic Cholenahally; Lee, Sau; Kaczkowski, Scott M; Kinlay, Scott; Hayes, Sean W; Sobczak, Sebastian; Asier, Senait; Sayganov, Sergey A; Sokol, Seth I; Pandie, Shaheen; Yahaya, Shaiful Azmi; Mehta, Shamir; Nie, Shao-Ping; Chandra, Sharad; Islam, Sharder; Tai, Sharon; Karwa, Sheetal Rupesh; Ussery, Sheri; Bajaj, Sheromani; Crook, Sherron C; Nishimura, Shigeyuki; Nakano, Shintaro; Heydari, Shirin; Choudhary, Shiv Kumar; Patel, Shivali; Ganesan, Shobana; Pandey, Shruti; Zhang, Shuyang; Hande, Shweta; Gadage, Siddharth; Tan, Sik-Yin V; Zottis Poletti, Silvia; Riera, Silvia; Valbuena, Silvia; Walsh, Simon; Maspoli, Simona; Savaris, Simone; Feng, Si-Ting; Cho, So Yang; Yakubov, Solomon; Zhu, Songlin; Wang, Songtao; Guerrero, Sonia; Gupta, Sonika; Salinger Martinovic, Sonja; Brons, Sonya; Brener, Sorin; Gurunathan, Sothinathan; Saba, Souheil; Nayak, Soundarya; Reddy, Sowjanya; Potluri, Srinivasa; Sudarshan, Sriram; Kuanprasert, Srun; Van Oosterhout, Stacie; Lerakis, Stamatios; Cobos, Stanley E; Bertog, Stefan C; Simović, Stefan M; Weikl, Stefan; Di Marco, Stefano; Provasoli, Stefano; Tirado, Stephanie A; Boer, Stephanie C; Lane, Stephanie M; Ferket, Stephanie; Kelly, Stephanie; Wasmiller, Stephanie; McKellar, Stephen H; Hoole, Stephen P; Fremes, Stephen; Preston, Stephen; Leung, Steve; Fein, Steven A; Lindsay, Steven J; Sedlis, Steven P; Giovannone, Steven; Michael, Steven; Weitz, Steven; van Vugt, Stijn; Banerjee, Subhash; Naik, Sudhir; Hosino, Suellen; Desire, Sukie; Yamwong, Sukit; Thambar, Suku T; Mookherjee, Sulagna; Singh, Suman; Mishra, Sundeep; Verma, Sunil Kumar; Kulthawong, Supap; Khwakhong, Supatchara; Naik, Surendra; Babu, Suresh; Woragidpoonpol, Surin; Narayanappa, Suryaprakash; Derbyshire, Susan; Gent, Susan; Mathus, Susan; Milbrandt, Susan; Moore, Susan; Regan, Susan; Stinson, Susan; Webber, Susan; Silva, Susana; Stevens, Susanna; Gruensfelder, Susanne; Aramcharoen, Suthara; Kolhe, Suvarna; Tavares, Suzana; Arnold, Suzanne; Welsh, Suzanne; Apostolovic, Svetlana; Kunhunny, Swapna; Hung, Ta-Chuan; Zappernick, Taissa; Sharir, Tali; Silva, Talita; Soares, Tamara Colaiácovo; Pillay, Tapan Umesh; Mittal, Tarun K; Trifonova, Tatiana; Duarte, Tauane Bello; Huk, Tauqir; Dutoiu, Téodora; Chua, Terrance; Weyand, Terry; Charles, Thabitha; Kofidis, Theodoros; McCreary, Theresa; Lefevre, Thierry; Arumairajah, Thippeekaa; Tepsuwan, Thitipong; Mulhearn, Thomas J; Meyer, Thomas M; Rocco, Thomas P; Downes, Thomas R; Crain, Thomas; Haldis, Thomas; Mathew, Thomas; Redick, Thomas; Devi, Thounaojam Indira; Nageh, Thuraia; Cauthren, Tia; Silva, Tiago; Little, Tiffany; Andric, Tijana; Harding, Tina; Lau, Titus; Formisano, Tiziana; Moccetti, Tiziano; Ciurus, Tomasz; Mazurek, Tomasz; Tarchalski, Tomasz; Nagai, Toshiyuki; Tran, Tri; Youn, Tricia; Tucker, Trish; Milner, Trudie; Bose, Tuhina; Kotecha, Tushar; Sechtem, Udo; Valeti, Uma S; Cucchini, Umberto; Badami, Umesh; Kaul, Upendra; Bahl, V K; Narain, V S; Casali, Valentina; Godoy, Valeria; Robesyn, Valerie; Priya, Vamshi P; Yadav, Vandana; McKinney, Vera; De Lenges, Veronica; Tinnirello, Veronica; Miro, Vicente; Navarro, Victor; Gumerova, Victoria; Hernandez, Victoria; Seeratan, Vidya; Kumar, Vijay; Kozulin, Vikentiy Y; Bulkley, Viktoria; Veiga, Vilmar Jr; Setang, Vincent; Vineeth, C P; Pubull Nuñez, Virginai; Fernández-Figares, Virginia; Gomes, Vitor; Gabriel, Viviana; Dos Santos, Viviane; Almeida, Viviane; Iliescu, Vlad A; Mudrenovic, Vladan; Dzavik, Vladimir; Giga, Vojislav L; Mogrovejo, Walter Enrique; Chan, Wan Xian; Marfori, Wanda C; Parker, Wanda; Mekara, Warangkana; Nona, Wassim; Old, Wayne; Pennachi, Wayne; Nawarawong, Weerachai; Chen, Wei; Su, Wei; Xing, Weibing; Lan, Wei-Ren; Crawford, Wenda; Stewart, Wendy L; Drewes, Wendy; Lin, Wenhua; Abernethy, William B; Salerno, William D; Fearon, William F; Vergoni, William; Weintraub, William; Sia, Winnie C; Musial, Wlodzimierz J; Flores-RÃos, Xacobe; Garcia-Moll Marimon, Xavier; Su, Xi; Ma, Xiang; Gu, Xiangqiong; Wang, Xiao; Li, Xiaomei; Yao, Xiaowei; Fu, Xin; Su, Xin; Zeng, Xin; Yang, Xinchun; Li, Xiuhong; Fang, Xuehua; Wang, Xutong; Geng, Yaming; Yan, Yan; Pépin-Dubois, Yanek; Wang, Yanfu; Wang, Yang; Tian, Yanmeng; Huang, Yaping; Han, Yechen; Zambrano, Yesenia; Yang, Yi-Hsuan; Sia, Ying Tung; Yang, Yining; Ma, Yitong; Peralta, Yolayfi; Wu, Yongjian; Kunwu, Yu; Zhao, Yu; Peng, Yudong; Lin, Yueh-Hung; Zhao, Yulan; Dong, Yumei; Zhao, Yunhai; Wannasopha, Yutthaphan; Taul, Yvonne; Sahul, Zakir; Kudzoeva, Zalina; Kalarus, Zbigniew; Markovic, Zeljko Z; Huang, Zhen; Ji, Zheng; Liu, Zhenyu; Yue, Zhou; Zhang, Zhulin; Li, Zhuxi; Singh Meharwal, Zile; Bai, Ziliang; Yu, Zixiang; Huda, Zohra; Davidovits, Zoltan
BACKGROUND:Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS:We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS:Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS:Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).
PMID: 32227755
ISSN: 1533-4406
CID: 5451242
Health-Status Outcomes with Invasive or Conservative Care in Coronary Disease
Spertus, John A; Jones, Philip G; Maron, David J; O'Brien, Sean M; Reynolds, Harmony R; Rosenberg, Yves; Stone, Gregg W; Harrell, Frank E; Boden, William E; Weintraub, William S; Baloch, Khaula; Mavromatis, Kreton; Diaz, Ariel; Gosselin, Gilbert; Newman, Jonathan D; Mavromichalis, Stavroula; Alexander, Karen P; Cohen, David J; Bangalore, Sripal; Hochman, Judith S; Mark, Daniel B; Ricci, Joseph; Tello Montoliu, A; Robero Aniorte, A I; Mulder, Abbey; Laddu, Abhay A; Goyal, Abhinav; Dubey, Abhishek; Goyal, Abhishek; Knighton, Abigail; Oomman, Abraham; Jaskowiak, Adam J; Kolodziej, Adam; Witkowski, Adam; Hameed, Adnan; Anesini, Adriana; Hussain, Afshan; Juceviciene, Agne; Urboniene, Agne; Jakal, Agnes; Szramowska, Agnieszka; Khairuddin, Ahmad; Abdel-Latif, Ahmed; Adel, Ahmed; Aljzeeri, Ahmed; Kamal, Ahmed; Talaat, Ahmed; Mann, Aimee; Contreras, Aira; Kumar, Ajit; Kumar, V K; Furukawa, Akemi; Bagai, Akshay; Smigelskaite, Akvile; Furber, Alain; Rheault, Alain; Loehr, Alaine Melanie; Rosen, Alan; Varga, Albert; Qelaj, Albertina; Barioli, Alberto; Russo, Aldo; Moorman, Alec; Gisbert, Alejandro; Fratczak, Aleksandra; Laucevicius, Aleksandras; Kuleshova, Alena; Sionis, Alessandro; Sirker, Alexander A; Chernyavskiy, Alexander M; Craft, Alexandra; Vazquez, Alexandra; Ciappina Hueb, Alexandre; Colafranseschi, Alexandre S; Schaan de Quadros, Alexandre; Tognon, Alexandre; Alghamdi, Ali; Manica Muller, Alice; Nogueira Rabaça, Aline; Peixoto Deiro, Aline; Hallam, Alison; Stone, Allegra; Schley, Allison; Castro, Almudena; Rabelo Ales, Alvaro; Germann, Amanda; O'Malley, Amanda; Uxa, Amar; Ojajuni, Amarachi; Oliveira, Amarino C Jr; Hull, Amber B; Roy, Ambuj; Zarka, Amer; Janmohamed, Amir; Brown, Ammani; Malinay, Ammy; Martinez Monzonis, Amparo; Richards, Amy J; Iskandrian, Amy; Ollinger, Amy; Djordjevic-Dikic, Ana D; Fernández MartÃnez, Ana; Gomes Almeida, Ana; Batista, Ana Paula; Francisco, Ana Rita; Mladenovic, Ana S; Santana, Ana; Siddiqui, Anam; Kuzmina-Krutetskaya, Anastasia M; Vertes, Andras; 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Valdespino-Estrada, Aquiles; Boan, Araceli; Ishani, Areef; Diaz, Ariel; Ghosh, Arijit; Prommintikul, Arintaya; Roberts, Arline; Seto, Arnold H; Good, Arnold P; Quyyumi, Arshed; Labovitz, Arthur J; Kerner, Arthur; Campos-Santaolalla, Arturo S; Misra, Arunima; Mukherjee, Ashok; Seth, Ashok; Seedhom, Ashraf; Cheema, Asim N; Ahmed, Asker; Mathur, Atul; Verma, Atul; Leong, Audrey W; Ã…kerblom, Axel; Fuentes, Axelle; Naher, Aynun; Valaiyapathi, Badhma; Kaur, Baljeet; Guruge, Bandula; BrzeziÅ„ska, Barbara; Nardi, Barbara; Czarniak, Bartosz; Singh, Bebek; Igual, Begoña; Merkely, Bela; Alvarez, Belen Cid; Spooner, Benjamin J; Chow, Benjamin J W; Cheong, Benjamin; Shah, Benoy N; de Bruyne, Bernard; Valecka, Bernardas; Jäger, Bernhard; Archer, Beth A; Abramson, Beth; Jorgenson, Beth; Harvey, Bethany; O'Neal, Betsy; Atkinson, Bev; Bozek, Bev; Lang, Bevin; Sasidharan, Bijulal; Yang, Bin; Zhang, Bin; Kurian, Binoy Mannekkattukudy; Goebel, Bjoern; Hu, Bob; Popescu, Bogdan A; Crnokrak, Bogdan; Zhu, Bolin; Kirby, Bonnie J; Zimbelman, Brandi D; Starks, Brandy; Beleslin, Branko D; Hart, Brenda; Shapiro, Brian P; McCandless, Brian; Wisniewski, Brianna; Smith, Brigham R; Mirrer, Brooks; McManus, Bruce; Rutkin, Bruce; Paulino, Bruna Edilena; Ascoli, Bruna Maria; Smith, Bryn; Allen, Byron J; Gibson, C Michael; Bairey Merz, C Noel; Pop, Calin; Hague, Cameron; Thais de Ormundo, Camila; Gopaul, Candace; Edillo, Candice P; Polanczyk, CarÃsi A; Krannila, Carita; Vicente, Carla; Gagné, Carl-Éric; Briguori, Carlo; Peña Gil, Carlos; Alvarez, Carlos; Ohmart, Carly; Beladan, Carmen C; Ginghina, Carmen; Kartje, Carol M; Alsweiler, Caroline; Brown, Caroline; Callison, Caroline; Pinheiro, Caroline; Rodgers, Caroline; Spindler, Caroline; Corbett, Carolyn; Drum, Carrie; Riedberger, Casey; Bone, Catherine; Fleming, Catherine; Gordon, Catherine; Jahrsdorfer, Catherine; Lemay, Catherine; Weick, Catherine; Patten, Cathrine; Goletto, Cecilia; Kepka, Cezary; Suvarna, Chandini; Xu, Chang; Mercure, Chantale; Viljoen, Charle A; Wiyarand, Charlene; Jia-Yin Hou, Charles; Lui, Charles Y; Cannan, Charles; Cornet, Charles; Pirro, Charlotte; Rimsukcharoenchai, Chataroon; Wang, Chen; Tsai, Cheng-Ting; Chien, Chen-Yen; Allardyce, Cheryl A; Hedgepeth, Chester M; Patel, Chetan; Attanasio, Chiara; Yen, Chih-Hsuan; Chow, Chi-Ming; Er, Ching Min; Ong, Ching-Ching; Manjunath, Cholenahally Nanjappa; Beck, Chris; Buller, Chris; Vassaliere, Christel; Hamm, Christian; Caldeira, Christiano; Ballantyne, Christie; Björklund, Christina; Hinton, Christine R; Bergeron, Christine; Masson, Christine; Roraff, Christine; Shelley, Christine; Laure, Christophe; Thuaire, Christophe; Kinsey, Christopher; McFarren, Christopher; Spizzieri, Christopher; Travill, Christopher; Liu, Chun-Chieh; Hung, Chung-Lieh; Li, Chunguang; Yun, Chun-Ho; Xia, Chunli; Heard, Ciarra; Schultz, Cidney; Venn-Edmonds, Clare; Hochberg, Claudia P; Wegmayr, Claudia; Cortés, Claudia; Escobar, Claudia; Freixo, Cláudia; Mesquita, Claudio T; Kadalie, Clemens T; Berry, Colin; Philander, Constance; Thobois, Corine; Costantini, Costantino; Page, Courtney; Atkinson, Craig; Barr, Craig; Paterson, Craig; Bare, Cristina; Baumann, Cynthia; Burman, Cynthia; Espinosa, Dalisa; Collison, Damien; Deleanu, Dan; Elian, Dan; Gao, Dan; Oliver, Dana; Vezina, Daniel P; O'Rourke, Daniel; Komar, Daniele; Schade, Danielle; Francis, Darrel P; Malaev, Dastan; Bull, David A; Winchester, David E; Faxon, David P; Booth, David; Cohen, David; DeMets, David; Foo, David; Schlichting, David; Taggart, David; Waters, David; Wohns, David; Vo, Davis; Teodorczyk, Dawid; Shelstad, Dawn; Turnbull, Dawn; Li, Dayuan; Kereiakes, Dean; O'Neill, Deborah; Yip, Deborah; Johnson, Debra K; Dees, Debra; Bhatt, Deepak L; Gopal, Deepika; Kumar, Deepti; Mattina, Deirdre; Murphy, Deirdre; Small, Delano R; Rose, Delsa K; Jiang, Dengke; Phaneuf, Denis Carl; Braganza, Denise; Fine, Denise; Cyr, Derek; Tobin, Desiree; Cukali, Diana; Parra, Diana; Camara, Diane; Minshall Liu, Diane; Vences, Diego Adrián; Franca de Cunha, Diego; 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Szczerba, Ewa; Wojtala, Ewelina; Ribeiro Silva, Expedito Eustáquio; Ortuño, F Marin; Farias, Fabio R; Fimiani, Fabio; Rolfo, Fabrizio; Yu, Fa-Chang; Hage, Fadi; Matar, Fadi; Haider Jafary, Fahim; Feng, Fang; Liu, Fang; Ranjbaran, Fatima; Rodriguez, Fatima; Pinto, Fausto J; Rashid, Fauzia; Ramani, Federica; Wang, Fei; Igansi, Fernanda; Silva, Filipa; Ottani, Filippo; Haines, Fiona; Al Solaiman, Firas; Egydio, Flávia; Lyra, Flavio; Egger, Florian; Farquharson, Fran; Laube, Frances; Carreras Costa, Francesc; de Micco, Francesca; Bianchini, Francesca; Pezzetta, Francesca; Pietrucci, Francesca; Orso, Francesco; Pisano, Francesco; Burt, Francis; Patuleia Figueiras, Francisca; Fernandez-Aviles, Francisco; Mongeon, Francois Pierre; Van de Werf, Frans; Guenther, Franziska; Witherow, Fraser N; Mohr, Fred; Dall'Orto, Frederico; Otsuka, Fumiyuki; De La Morena, G; Karthikeyan, G; Dekany, Gabor; Kerecsen, Gabor; Galeote, Gabriel; Grossmann, Gabriel; Vorobiof, Gabriel; Sanchez de Souza, Gabriela; Guzman, Gabriela; Zeballos, Gabriela; Gabrielli, Gabriele; Jakl-Kotauschek, Gabriele; Shammas, Gail A; Brandt, Gail; Chen, Gang; Lane, Gary E; Luckasen, Gary J; Sharma, Gautam; Mikolaitiene, Gelmina; Yee, Gennie; Nickenig, Georg; Revtyak, George E; Juang, George J; Fletcher, Gerald; Leonard, Gerald; Devlin, Gerard Patrick; Esposito, Gerard; Ãgoston, Gergely; Lamas, Gervasio; Fontos, Geza; Mikhail, Ghada; Cobb, Gia; Perna, Gian Piero; Leone, Gianpiero; Roditi, Giles; Barone-Rochette, Gilles; Mishra, Girish; Tarantini, Giuseppe; Wong, Glenda; Hamroff, Glenn S; Rayos, Glenn; Cheng, Gong; Barge-Caballero, Gonzalo; Davidović, Goran; Stankovic, Goran; Stevanovic, Gordana; Jingyan Wang, Grace; Young, Grace M; Wayser, Graceanne; Scaro, Graciela; Hillis, Graham S; Wong, Graham; Szulczyk, Grazyna Anna; Simonis, Gregor; Kumkumian, Gregory; Peichel, Gretchen Ann; Gajos, Grzegorz; Steinmaurer, Gudrun; Rucatti, Guilherme G; Portugal, Guilherme; Cantinho Lopes, Guilhermina; Pons Lladó, Guillem; Frostfelt, Gunnar; Wander, Gurpreet S; 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Schnittger, Ingela; Karimullah, Iqbal; Dauber, Ira M; Rehman, Iram; Peovska Mitevska, Irena; Marthe Lang, Irene; Subbotina, Irina; Kalibataite-Rutkauskiene, Irma; Yusnida, Irni; Carvajal, Isabel Estela; Palazzo, Isabella C; Hogan, Isabelle; Roy, Isabelle; Syed, Ishba; Tejani, Ishita; Naryshkin, Ivan A; Jankovic, Ivana; Niedzwiecka, Iwona; Knight, J David; Kusmierek, Jacek; White, Jackie M; Chow, Jackie; Udell, Jacob; Tamis-Holland, Jacqueline E; Fannon, Jacqueline; Quin, Jacquelyn A; Do, Jacquelyn; Heo, Jaekyeong; Maksym, Jakub; Davies, James E; O'Keefe, James H Jr; Jang, James J; Cha, James; Harrison, James; Hirsch, James; Stafford, James; Tatoulis, James; Rankin, Jamie; Henzel, Jan; Orga, Jan; Tancredi, Jana; Oliveira, Janaina; Burton, Jane; Eckstein, Jane; Marucci, Jane; Knight, Janet P; Blount, Janet; Halliday, Janet; Kourzenkova, Janetta; Raj, Janitha; Sinning, Jan-Malte; Pozzibon, Jaqueline; Drozdz, Jaroslaw; Karwowski, Jaroslaw; Glover, Jason D; Kwok, Jason Loh; Call, Jason T; Linefsky, Jason; Gomes, Jassira; Anumpa, Jati; Garcia, Javier J; Courtis, Javier; Meisner, Jay; Jayakumar, K; Scales, Jayne; Denaro, Jean E; Juliard, Jean Michel; Ho, Jean; Stansborough, Jeanette K; Juliard, Jean-Michel; Russo, Jeanne; Schoep, Jeannette J M; Thambyrajah, Jeet; Leimberger, Jeff; Breall, Jeffery A; Kohn, Jeffrey A; Milliken, Jeffrey C; Anderson, Jeffrey; Blume, Jeffrey; Kanters, Jeffrey; Lorin, Jeffrey; Moses, Jeffrey; Stepanovic, Jelena J; Celutkiene, Jelena; Djokic, Jelena; Stojkovic, Jelena; Jose, Jenne M; Manchery, Jenne; Mull, Jennifer A; Czerniak, Jennifer H; Stanford, Jennifer L; Gillis, Jennifer; Horst, Jennifer; Isaacs, Jennifer; Langdon, Jennifer; Thomson, Jennifer; Tomfohr, Jennifer; White, Jennifer; Kuo, Jen-Yuan; Rautureau, Jeremy; Fleg, Jerome; Berg, Jessica; Rodriguez, Jessica; Waldron, Jessica; Patro, Jhina; Li, Jia; Mao, Jiajia; Liu, Jiamin; Wang, Jian'an; Li, Jianhua; Zhang, Jianxin; Qi, Jie; Lyo, Jihyun; Marcus, Jill; Blankenship, Jim; Zhang, Jing; Liu, Jingjing; Fan, Jing-Yao; Li, Jiun-Yi; Pradhan, Jiwan; Chen, Jiyan; Rivera Caravaca, J M; Evans, Jo; Garcia Picart, Joan; Hecht, Joan; Jaroch, Joanna; Zalewska, Joanna; Kelly, Joanne; Taaffe, Joanne; Abbud, João Reynaldo; Vitola, João V; Peñafiel, JoaquÃn V; Benatar, Jocelyne; Bindeman, Jody; Sabik, Joe; Klitch, Joel; Christopher, Johann; Aspberg, Johannes; Friedman, John D; Beltrame, John F; Heitner, John F; Graham, John Joseph; Davies, John R; Doan, John; Kotter, John; Kurian, John; Mukai, John; Pownall, John; Sobolewska, Jolanta; Kobashigawa, Jon; Goldberg, Jonathan L; Bazeley, Jonathan W; Byrne, Jonathan; Himmelfarb, Jonathan; Leipsic, Jonathan; Thorsen, Jonean; Trejo Gutierrez, Jorge F; Escobedo, Jorge; Timmer, Jorik; Ortega-RamÃrez, José A; Marin-Neto, José Antonio; Salas, Jose D; Castillo, Jose Enrique; Saraiva, Jose Francisco; Cuenca-Castillo, José J; Diez, Jose L; Narro Villanueva, José Luis; da Vieira, José Luiz; Flores-Palacios, José M; Gonzalez, Jose Ramon; Seijas Amigo, Jose; Fragata, Jose; Padró, Josep Maria; McGarvey, Josheph F X Jr; Hannan, Joseph; Sacco, Joseph; Sweeny, Joseph; Wiesel, Joseph; Abraham, Josephine D; Loh, Joshua P; Burkhardt, Joy; White, Joyce R; Riestenberg-Smith, Joyce; Sebo, Judit; Meadows, Judith L; Wright, Judith; Foltz, Judy Mae; Hung, Judy; Otis, Judy; Stumpf, Juergen; Tsai, Jui-Peng; Dionne, Julia S; de Aveiro Morata, Julia; Bunke, Julie; Morrow, Julie; Figal, Julio César; Fujita, Jun; Jiang, Jun; Li, Junhua; Yang, Junqing; Euathrongchit, Juntima; Garg, Jyotsna; Manjula Rani, K; Preethi, K; Goetschalckx, Kaatje; Eggers, Kai; Surineni, Kamalakar; Hirase, Kanae; Kapilamoorthy, T R; Calfas, Karen; Gratrix, Karen; Hallett, Karen; Hultberg, Karen; Nugent, Karen; Petrosyan, Karen; Swan, Karen; Kryczka, Karolina; Wojtczak-Soska, Karolina; Wojtera, Karolina; Lenk, Karsten; Ramasamy, Karthik; Åuczak, Katarzyna; Malinowska, Katarzyna; Pointon, Kate; Robb, Kate; Martin, Katherine; Claes, Kathleen; Carruthers, Kathryn; Siegel, Kathy E; Drouin, Katia; Fowler-Lehman, Katie; Rawat, Kavita; Rowe, Kay; Fukuda, Keiichi; Fox, Keith A A; Mahaffey, Ken; Unterbrink, Kendra; Giedd, Kenneth; Van Loo, Kerrie; Lee, Kerry; Bonin, Kerstin; Bainey, Kevin R; Harley, Kevin T; Anstrom, Kevin; Chan, Kevin; Croce, Kevin; Landolfo, Kevin; Marzo, Kevin; Patel, Keyur; Abdul-Nour, Khaled; Alfakih, Khaled; Dajani, Khaled; Ziada, Khaled; Baloch, Khaula; Kushniriuk, Khrystyna; Poh, Kian-Keong; Ireland, Kim F; Holland, Kim; Byrne, Kimberly Ann; Halverson, Kimberly E; Elmore, Kimberly; Miller-Cox, Kimberly; Reddy, Kiran; Quiles, Kirsten J; Abercrombie, Kirsty; Matschke, Klaus; Szymczyk, Konrad; Chan, Koo Hui; Preethi, Kotiboinna; Sokhon, Kozhaya; Meemuk, Krissada; Thygesen, Kristian; Salmi, Kristin M; Newby, Kristin; Wippler, Kristina; Arges, Kristine; Teoh, Kristine; Etherington, Krystal; Åoboz-GrudzieÅ„, Krystyna; Reczuch, Krzysztof W; Bury, Krzysztof; Drzymalski, Krzysztof; KukuÅ‚a, Krzysztof; Sung, Kuo-Tzu; Huber, Kurt; Douangvila, Ladda; Sullenberger, Lance; Trama, Larissa Miranda; Matics, Laszlone; Drew, Laura; Flint, Laura; Keinaite, Laura; Sarti, Laura; Kolakaluri, Laurel; Phillips, Lawrence M; Friedman, Lawrence; Phillips, Lawrence; Velicki, Lazar; Howell, Leah; Maranan, Leandro C; Cox, Leanne; Daba, Ledjalem; Zhang, Lei; Dharmarajan, Lekshmi; Bockeria, Leo; Pizzol Caetano, Leonardo; Bridi, Leonardo; Bershtein, Leonid L; Sokalski, Leszek; Yan, Li Hai; Li, Li; Nijmeijer, Lia; Sousa, Lidia; Xu, Lihong; Zhang, Lihua; Zhang, Lili; Schiavi, Lilia; Barbosa, Lilian Mazza; Khor, Lillian L; Felix-Stern, Lina; Hall, Linda L; Hollenweger, Linda M; Arcand, Linda; Davidson-Ray, Linda; Schwarz, Linda; Sikora, Lindsey N; Chi, Lingping; Patricio, Lino; Zhang, Liping; Chaytor, Lisa; Hatch, Lisa; McCloy, Lisa; Wong, Lisa; Persson, Liselotte; Jiang, Lixin; Low, Liz; Pupic, Ljiljana; Bière, Loïc; Monti, Lorenzo; Christensen, Lori; Pritchard, Lori; Black, Loriane; Desimone, Lori-Ann; Larmand, Lori-Ann; McGregor, Lorraine; Morby, Louise; Thomson, Louise; Harvey, Luc; de Pádua Baptista, Luciana; Garcia, Lucilla; Eliahou, Ludivine; Helmer, Ludmila; Smidt, Luis F; Bernanrdes, Luis; Guzman, Luis; Carvalho, Luiz A; Xiong, Luyang; Teo, Lynette L; Neeson, Lynn M; Winstanley, Lynne; Srichai-Parsia, M Barbara; Quintana Giner, M; Sowjanya Reddy, M; Valdés Chávarri, M; Grazia Rossi, M; Simoons, Maarten; Konigstein, Maayan; Lesiak, Maciej; Olsowka, Maciej; Selas, Mafalda; Corfias, Magalie; Madero Rovalo, Magdalena; Åanocha, Magdalena; Miller, Magdalena; Misztal-Teodorczyk, Magdalena; Rantinella, Magdalena; Abdelhamid, Magdy; Jimenez, Magnolia; Alam, Mahboob; Mylarappa, Mahevamma; El Shahawy, Mahfouz; Mohamed, Mahmoud; Al-Bustami, Mahmud; Joseph, Majo X; Frach, Malgorzata; CeliÅ„ska-Spodar, MaÅ‚gorzta; Helm, Malte; Chacko, Manas; Murphy, Mandy; Vinod, Manitha; Rani, Manjula; Dhawan, Manu; Mombelli, Manuela; Weber, Marcel; Galvani, Marcello; Rodrigues, Marcelo Jamus; Dubin, Marcia F; Werner Bayer, Marcia F; Szkopiak, Marcin; Monsalve, Marco Antonio; Santos, Marco Bizzaro; Magnoni, Marco; Marini, Marco; Sicuro, Marco; Zenati, Marco; Coimbra Resende, Marcos Valério; Roik, Marek; Bentzvi, Margalit; Gilsenan, Margaret; Iraola, Margaret; Quinn, Margot C; Alfonso, Maria A; Pereira Moraes, Maria Antonieta; MartÃnez-RuÃz, MarÃa Dolores; Canales, MarÃa Fernanda; Caetano, Maria Inês; Corral, Maria P; Pérez GarcÃa, Maria; Actis, Maria Victoria; Aguirre, Maria; Andreasson, Maria; Aprile, Maria; Colton, Maria; Martin, Maria Eugenia; Lasala, Maria; Lorenzo, Maria; Posada, Maria; Shier, Maria; Thottam, Maria; Furtado, Mariana V; Okada, Mariana Yumi; Dracoulakis, Marianna D A; De Andrade, Marianne; Rubio, Mariano; Essermark, Marie; Scherrer-Crosbie, Marielle; Petrovic, Marija T; Zdravkovic, Marija; Black, Marilyn; Garcia, Marina; Garcia, Mario J; Szulik, Mariola; Orgera, Marisa; de Belder, Mark A; Harbinson, Mark; Hyun, Mark; Peterson, Mark; Xavier, Mark; Mosley, Marlowe; Capinha, Marta; Marcinkiewicz-Siemion, Marta; Swiderek, Marta; Meyer, Martha; Ceseri, Martina; Tricoli, Martina; Kronenberg, Marvin; Williams, Mary; Champagne, Mary Ann; Rogge, Mary Colleen; Soltau, Mary R; Streif, Mary; Villella, Massimo; Leesar, Massoud; Claudia, Matei; Solecki, Mateusz; Mungo, MatÃas Nicolás; Wall, Matthew Jr; Budoff, Matthew; Jezior, Matthew; Luckie, Matthew; Friedrich, Matthias; Haeffner, Mauren P; Tscharre, Maximilian; Winter, Max-Paul; Almeida, Mayana; Krishnam, Mayil S; Patel, Mayuri; Mishra, Meenakshi; Manocchia, Megan; Kakade, Meghana; Munro, Melanie J; Chaplin, Melissa D; LeFevre, Melissa; Andiapen, Mervyn; Gibson, Michael A; Rubens, Michael B; Turner, Michael C; Shapiro, Michael D; Lee, Michael W; Berlowitz, Michael; Davidson, Michael; Mack, Michael; McDaniel, Michael; Mumma, Michael; Wlodarczyk, Michal; Khouri, Michel G; Slama, Michel S; Rawlins, Michele; Bonner, Michelle M; Seib, Michelle M; Chang, Michelle; Crowder, Michelle; Dixon, Michelle; Mayon, Michelle; McEvoy, Michelle; Yee, Michelle; Fernandes, Miguel M; Nobre Menezes, Miguel; Souto Bayarri, Miguel; Barrero, Miguel; Torosoff, Mikhail T; Dobric, Milan R; Dobric, Milan; Dekleva, Milica Nikola; Gadkari, Milind Avdhoot; Gomez, Millie; Kyaw, Min Tun; Brooks, Miriam; Stevo Martinovic, Miroslav; Lustre, Mitchel B; Vakani, Mohammad Tariq; El-Hajjar, Mohammad; Al-Amoodi, Mohammed; Hussain, Mohammed; Saleem, Mohammed; Blanco-Calvo, Moisés; Jiménez-Santos, Moisés; Bhatia, Mona; Rosca, Monica; Laukyte, Monika; Gracida Blanca, Montserrat; Vila Perales, Montserrat; Al-Mallah, Mouaz H; de Oliveira Filho, Moysés; Ntsekhe, Mpiko; Saric, Muhamed; Chen, Mulei; Brousseau, Myriam; Takiuti, Myrthes Emy; Cemerlic-Adjic, Nada; Asif, Nadia; Gakou, Nadia; Hussain, Nafisa; Katamadze, Nana O; Clapp, Nancy L; Aedy, Nancy; Nataraj, Nandita; Wenger, Nanette K; Uchida, Naomi; Ismail, Nasrul; Oliveira, Natalia S; de Carvalho Maffei, Natalia; Spitzer, Natalie; Putnam, Natasha C; Aslam, Naved; Mowafy, Neamat; Pandit, Neeraj; Parakh, Neeraj; Garcevic, Nevena; Meadows, Ngaire; Tran, Nhi N; Danchin, Nicholas; Lakeman, Nicki; Johnston, Nicola; Shammas, Nicolas W; Saint Vrestil, Nicole; Deming, Nicole; Zhong, Nier; Patel, Niket; Boskovic, Nikola N; Karogiannis, Nikolaos; Werner, Nikos; Johnston, Nina; Zhang, Ning; Zhou, Ning; Hindoyan, Niree; Kumar, Nirmal; Chadha, Nitika; Naik, Nitish; Aripova, Nodira; Mtana, Noloyiso; Eskelson, Nona A; Mokhtar, Noor Syamira; Taksaudom, Noppon; Basri, Nor Asiah; Marchelletta, Nora; Hogg, Norma; Jungla, Nungshi; Ferreira, Nuno; Lubyanaya, Oksana A; Nikolaeva, Olga B; Cañavate, Olga; Sobrino, Olga; Walesiak, Olga; Walter, Olga; ZdoÅ„czyk, Olga; Lim, Olivia J; Anaya, Olivia; Mancilla, Olivia; Dubourg, Olivier; Bello, Olugbenga; Almousalli, Omar; Thompson, Omar; Olurinde, Oni; Harel, Or; Raheem, Osama; Méndiz, Oscar; Prada-Delgado, Óscar; Shapira, Oz; Schulze, P Christian; Panpunuan, Pachara; Maurovich-Horvat, Pal; Garg, Pallav; Moraga, Paloma; Singh, Pam; Julian, Pamela; Ouyang, Pamela; Sigel, Pamela; Woodard, Pamela; Zhou, Panpan; Poggio, Paola Emanuela; Smanio, Paola; Calabro, Paolo; Jeetley, Paramjit; Goube, Pascal; Nguyen, Patricia K; Alarie, Patricia; Arakelian, Patricia; Arsenault, Patricia; Blaise, Patricia; Brito, Patricia; Cowper, Patricia; Endsley, Patricia; Mieses, Patricia; Alexander, Patrick B; Donnelly, Patrick; Wilmot, Patrick; Lebioda, Patrycja; Gordon, Paul C; Mesropian, Paul Der; Galiwango, Paul; Hauptman, Paul; Kennedy, Paul; Beardsley, Paula; GarcÃa-González, Paula; Rezende, Paulo Cury; Caramori, Paulo Ricardo; Kozlov, Pavel S; Canas Silva, Pedro; Melo Barros E Silva, Pedro Gabriel; PÃccaro de Oliveira, Pedro; Carvalho, Pedro; Modas, Pedro; Rio, Pedro; Jain, Peeyush; He, Peiyu; McCullough, Peter A; Stone, Peter H; Pollak, Peter M; Douglass, Peter; Henriksen, Peter; OKane, Peter; Ong, Peter; Jones, Philip; Rogal, Philip; Généreux, Philippe; Menasche, Philippe; Rheault, Philippe; Goold, Phoebe; Gervais, Pierre; Michaud, Pierre; Calvillo, Pilar; Chai, Ping; Jakubowski, Piotr; Pruszczyk, Piotr; Slomka, Piotr; Sritara, Piyamitr; Loh, Poay-Huan; Sonawane, Poonam; Samadi, Pouneh; Parikh, Pragnesh P; Deedwania, Prakash; Patel, Pranav M; Polamuri, Praneeth; Sharma, Pratiksha; Vasquez, Precilia; Kamath, Preeti; Thomas, Prince; Arambam, Priyadarshani; Mehta, Puja K; Grant, Purvez; Naik, Pushpa; Zhong, Qi; Zhao, Qian; Zhou, Qiang; Yuan, Qianqian; Yu, Qin; Li, Qingxian; Xie, Qiulan; Zeng, Qiutang; Vindhya, R J; Gerlach, R James; King, Rachel; VuÄić, Rada; Lyubarova, Radmila; Pracon, Radoslaw; Fisher, Raewyn; Beyar, Rafael; Diaz, Rafael; Selgas, Rafael; Bugiardini, Raffaele; Fanelli, Raffaele; Kavalakkat, Raisa; Rajalekshmi, V S; Barua, Rajat S; Menon, Rajeev; Nair, Rajesh Gopalan; Francis, Rajesh; Narang, Rajiv; Yadav, Rakesh; Huston, Ralph Alan; Ramakrishnan, T; de Silva, Ramesh; Mahmoud, Rami El; Carvalho, Ramiro; de Jesús-Pérez, Ramon; Stevens, Ramona; Leng, Ran; Kachru, Ranjan; Nath, Ranjit Kumar; Sanchez, Raquel; Dwyer, Raven R; Lee, Raven; Wyman, Ray; Wong, Raymond C; Little, Raymond W; Ocaranza Sanchez, Raymundo; Wimmer, Rebecca J; Bariciano, Rebecca; Otis, Rebecca; Herrmann, Rebekah R; Yunis, Reem; Hampson, Reinette; Karam, Renato Abdala; Hessian, Renee C; Kaneshiro, Renee; Ravindran, Reshma; Gamma, Reto Andreas; Bhandari, Reyna; Arsanjani, Reza; Lopes, Ricardo L; Mendes Oliveira, Ricardo; Costa, Ricardo; Bhatt, Richa; Davies, Richard F; Trimlett, Richard H J; Goldweit, Richard; Hermanides, Rik; Nakanishi, Rine; Sidh, Rinu R; Patel, Risha; Coram, Rita; Siddiqui, Rizwan A; Beanlands, Rob S; Hamburger, Robert J; Riezebos, Robert K; Donnino, Robert M; Bojar, Robert; Chilton, Robert; Guyton, Robert; Henderson, Robert; Kornberg, Robert; Leber, Robert; Mao, Robert; Stenberg, Robert; Santos, Roberta P; Favaloro, Roberto René; Amati, Roberto; Lima, Rodolfo G S D; Cerci, Rodrigo J; Tumelero, Rogerio; Tandon, Rohit; Tewari, Roma; Miranda-Peats, Romalisa; Wald, Ron; Mastouri, Ronald A; Morford, Ronald G; Schwartz, Ronald G; Pedalino, Ronald P; Hu, Rongrong; Hansen, Ronnell A; Cohen, Ronny A; Hachamovitch, Rory; Homem, Rosa; Sandonato, Rosa; Laimer, Rosane; Gans, Rosann; Yost, Roxanne; Mathew, Roy; Baleón-Espinosa, Rubén; Ramos, Ruben; Gevorgyan, Rubine; Ferreira, Rui; Jing, Rui; Pérez-Fernández, Ruth; Dwivedi, S K; Ramakrishnan, S; Khan, Saadat; Bokhari, Sabahat; Thomas, Sabu; Lubna, Sadath; Khan, Sajeeda Parveen; Govindan, Sajeev Chakanalil; Girotra, Saket; Kassam, Saleem; Canada, Sallie; Cruz-Flores, Salvador; Mohamed, Samaa; Ly, Samantha; El Kaffas, Sameh; Massalha, Samia; Setty, Sampoornima; Nwosu, Samuel; Seth, Sandeep; Singh, Sandeep; Niehe, Sander R; Rivest, Sandra M; Zier, Sandra S; Ahoud, Sandra; Carr, Sandy; Ganapathi, Sanjay; Shetty, Sanjay; Sharma, Sanjeev; Jimenez, Santa; Satheesh, Santhosh; Garcia, Santiago A; Fernandez, Sara; Karlsson, Sara; Salkind, Sara; Temiyasathit, Sara; Medina Rodriguez, Sarah; Beaudry, Sarah; Hadjih, Sarah; Williams, Sarah; Zahrani, Sarah; Ralhan, Sarju; Hinic, Sasa; Kedev, Sasko; Singh, Satinder; Yasuda, Satoshi; Manjunath, Satvic Cholenahally; Lee, Sau; Kaczkowski, Scott M; Kinlay, Scott; Hayes, Sean W; Sobczak, Sebastian; Asier, Senait; Sayganov, Sergey A; Sokol, Seth I; Pandie, Shaheen; Yahaya, Shaiful Azmi; Mehta, Shamir; Nie, Shao-Ping; Chandra, Sharad; Islam, Sharder; Tai, Sharon; Karwa, Sheetal Rupesh; Ussery, Sheri; Bajaj, Sheromani; Crook, Sherron C; Nishimura, Shigeyuki; Nakano, Shintaro; Heydari, Shirin; Choudhary, Shiv Kumar; Patel, Shivali; Ganesan, Shobana; Pandey, Shruti; Zhang, Shuyang; Hande, Shweta; Gadage, Siddharth; Tan, Sik-Yin V; Zottis Poletti, Silvia; Riera, Silvia; Valbuena, Silvia; Walsh, Simon; Maspoli, Simona; Savaris, Simone; Feng, Si-Ting; Cho, So Yang; Yakubov, Solomon; Zhu, Songlin; Wang, Songtao; Guerrero, Sonia; Gupta, Sonika; Salinger Martinovic, Sonja; Brons, Sonya; Brener, Sorin; Gurunathan, Sothinathan; Saba, Souheil; Nayak, Soundarya; Reddy, Sowjanya; Potluri, Srinivasa; Sudarshan, Sriram; Kuanprasert, Srun; Van Oosterhout, Stacie; Lerakis, Stamatios; Cobos, Stanley E; Bertog, Stefan C; Simović, Stefan M; Weikl, Stefan; Di Marco, Stefano; Provasoli, Stefano; Tirado, Stephanie A; Boer, Stephanie C; Lane, Stephanie M; Ferket, Stephanie; Kelly, Stephanie; Wasmiller, Stephanie; McKellar, Stephen H; Hoole, Stephen P; Fremes, Stephen; Preston, Stephen; Leung, Steve; Fein, Steven A; Lindsay, Steven J; Sedlis, Steven P; Giovannone, Steven; Michael, Steven; Weitz, Steven; van Vugt, Stijn; Banerjee, Subhash; Naik, Sudhir; Hosino, Suellen; Desire, Sukie; Yamwong, Sukit; Thambar, Suku T; Mookherjee, Sulagna; Singh, Suman; Mishra, Sundeep; Verma, Sunil Kumar; Kulthawong, Supap; Khwakhong, Supatchara; Naik, Surendra; Babu, Suresh; Woragidpoonpol, Surin; Narayanappa, Suryaprakash; Derbyshire, Susan; Gent, Susan; Mathus, Susan; Milbrandt, Susan; Moore, Susan; Regan, Susan; Stinson, Susan; Webber, Susan; Silva, Susana; Stevens, Susanna; Gruensfelder, Susanne; Aramcharoen, Suthara; Kolhe, Suvarna; Tavares, Suzana; Arnold, Suzanne; Welsh, Suzanne; Apostolovic, Svetlana; Kunhunny, Swapna; Hung, Ta-Chuan; Zappernick, Taissa; Sharir, Tali; Silva, Talita; Soares, Tamara Colaiácovo; Pillay, Tapan Umesh; Mittal, Tarun K; Trifonova, Tatiana; Duarte, Tauane Bello; Huk, Tauqir; Dutoiu, Téodora; Chua, Terrance; Weyand, Terry; Charles, Thabitha; Kofidis, Theodoros; McCreary, Theresa; Lefevre, Thierry; Arumairajah, Thippeekaa; Tepsuwan, Thitipong; Mulhearn, Thomas J; Meyer, Thomas M; Rocco, Thomas P; Downes, Thomas R; Crain, Thomas; Haldis, Thomas; Mathew, Thomas; Redick, Thomas; Devi, Thounaojam Indira; Nageh, Thuraia; Cauthren, Tia; Silva, Tiago; Little, Tiffany; Andric, Tijana; Harding, Tina; Lau, Titus; Formisano, Tiziana; Moccetti, Tiziano; Ciurus, Tomasz; Mazurek, Tomasz; Tarchalski, Tomasz; Nagai, Toshiyuki; Tran, Tri; Youn, Tricia; Tucker, Trish; Milner, Trudie; Bose, Tuhina; Kotecha, Tushar; Sechtem, Udo; Valeti, Uma S; Cucchini, Umberto; Badami, Umesh; Kaul, Upendra; Bahl, V K; Narain, V S; Casali, Valentina; Godoy, Valeria; Robesyn, Valerie; Priya, Vamshi P; Yadav, Vandana; McKinney, Vera; De Lenges, Veronica; Tinnirello, Veronica; Miro, Vicente; Navarro, Victor; Gumerova, Victoria; Hernandez, Victoria; Seeratan, Vidya; Kumar, Vijay; Kozulin, Vikentiy Y; Bulkley, Viktoria; Veiga, Vilmar Jr; Setang, Vincent; Vineeth, C P; Pubull Nuñez, Virginai; Fernández-Figares, Virginia; Gomes, Vitor; Gabriel, Viviana; Dos Santos, Viviane; Almeida, Viviane; Iliescu, Vlad A; Mudrenovic, Vladan; Dzavik, Vladimir; Giga, Vojislav L; Mogrovejo, Walter Enrique; Chan, Wan Xian; Marfori, Wanda C; Parker, Wanda; Mekara, Warangkana; Nona, Wassim; Old, Wayne; Pennachi, Wayne; Nawarawong, Weerachai; Chen, Wei; Su, Wei; Xing, Weibing; Lan, Wei-Ren; Crawford, Wenda; Stewart, Wendy L; Drewes, Wendy; Lin, Wenhua; Abernethy, William B; Salerno, William D; Fearon, William F; Vergoni, William; Weintraub, William; Sia, Winnie C; Musial, Wlodzimierz J; Flores-RÃos, Xacobe; Garcia-Moll Marimon, Xavier; Su, Xi; Ma, Xiang; Gu, Xiangqiong; Wang, Xiao; Li, Xiaomei; Yao, Xiaowei; Fu, Xin; Su, Xin; Zeng, Xin; Yang, Xinchun; Li, Xiuhong; Fang, Xuehua; Wang, Xutong; Geng, Yaming; Yan, Yan; Pépin-Dubois, Yanek; Wang, Yanfu; Wang, Yang; Tian, Yanmeng; Huang, Yaping; Han, Yechen; Zambrano, Yesenia; Yang, Yi-Hsuan; Sia, Ying Tung; Yang, Yining; Ma, Yitong; Peralta, Yolayfi; Wu, Yongjian; Kunwu, Yu; Zhao, Yu; Peng, Yudong; Lin, Yueh-Hung; Zhao, Yulan; Dong, Yumei; Zhao, Yunhai; Wannasopha, Yutthaphan; Taul, Yvonne; Sahul, Zakir; Kudzoeva, Zalina; Kalarus, Zbigniew; Markovic, Zeljko Z; Huang, Zhen; Ji, Zheng; Liu, Zhenyu; Yue, Zhou; Zhang, Zhulin; Li, Zhuxi; Singh Meharwal, Zile; Bai, Ziliang; Yu, Zixiang; Huda, Zohra; Davidovits, Zoltan
BACKGROUND:In the ISCHEMIA trial, an invasive strategy with angiographic assessment and revascularization did not reduce clinical events among patients with stable ischemic heart disease and moderate or severe ischemia. A secondary objective of the trial was to assess angina-related health status among these patients. METHODS:We assessed angina-related symptoms, function, and quality of life with the Seattle Angina Questionnaire (SAQ) at randomization, at months 1.5, 3, and 6, and every 6 months thereafter in participants who had been randomly assigned to an invasive treatment strategy (2295 participants) or a conservative strategy (2322). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate differences between the treatment groups. The primary outcome of this health-status analysis was the SAQ summary score (scores range from 0 to 100, with higher scores indicating better health status). All analyses were performed in the overall population and according to baseline angina frequency. RESULTS:At baseline, 35% of patients reported having no angina in the previous month. SAQ summary scores increased in both treatment groups, with increases at 3, 12, and 36 months that were 4.1 points (95% credible interval, 3.2 to 5.0), 4.2 points (95% credible interval, 3.3 to 5.1), and 2.9 points (95% credible interval, 2.2 to 3.7) higher with the invasive strategy than with the conservative strategy. Differences were larger among participants who had more frequent angina at baseline (8.5 vs. 0.1 points at 3 months and 5.3 vs. 1.2 points at 36 months among participants with daily or weekly angina as compared with no angina). CONCLUSIONS:In the overall trial population with moderate or severe ischemia, which included 35% of participants without angina at baseline, patients randomly assigned to the invasive strategy had greater improvement in angina-related health status than those assigned to the conservative strategy. The modest mean differences favoring the invasive strategy in the overall group reflected minimal differences among asymptomatic patients and larger differences among patients who had had angina at baseline. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).
PMID: 32227753
ISSN: 1533-4406
CID: 5451262
PD-L1 Testing for Lung Cancer in 2019: Perspective from the IASLC Pathology Committee
Lantuejoul, Sylvie; Tsao, Ming Sound-; Cooper, Wendy A; Girard, Nicolas; Hirsch, Fred R; Roden, Anja C; Lopez-Rios, Fernando; Jain, Deepali; Chou, Teh-Ying; Motoi, Noriko; Kerr, Keith M; Yatabe, Yasushi; Brambilla, Elisabeth; Longshore, John; Papotti, Mauro; Sholl, Lynette M; Thunnissen, Erik; Rekhtman, Natasha; Borczuk, Alain; Bubendorf, Lukas; Minami, Yuko; Beasley, Mary Beth; Botling, Johan; Chen, Gang; Chung, Jin-Haeng; Dacic, Sanja; Hwang, David; Lin, Dongmei; Moreira, Andre; Nicholson, Andrew G; Noguchi, Masayuki; Pelosi, Giuseppe; Poleri, Claudia; Travis, William; Yoshida, Akihiko; Daigneault, Jillian B; Wistuba, Ignacio I; Mino-Kenudson, Mari
The recent development of immune checkpoint inhibitors (ICI) has led to promising advances in the treatment of non-small cell and small cell lung cancer patients with advanced or metastatic disease. Most of ICI target the PD-1/PD-L1 axis with the aim of restoring anti-tumor immunity. Multiple clinical trials for ICI have examined a predictive value of PD-L1 protein expression in tumor cells and/or tumor-infiltrating immune cells by immunohistochemistry (IHC), for which different assays with specific IHC platforms were applied. Of those, some PD-L1 IHC assays have been validated for the prescription of the corresponding agent for first- or second-line treatment. However, not all laboratories are equipped with the dedicated platforms and many laboratories have set up in-house or laboratory developed tests, which are more affordable than generally expensive clinical trial-validated assays. Although PD-L1 IHC test is now deployed in the most pathology laboratories, its appropriate implementation and interpretation are critical as a predictive biomarker and can be challenging due to the multiple antibody clones and platforms or assays available and given the typically small size of samples provided. As many articles have been published since the issue of the IASLC Atlas of PD-L1 immunohistochemistry testing in lung cancer, this review by the IASLC pathology committee provides updates on the indications of ICI for lung cancer in 2019, and discusses important considerations on pre-analytical, analytical and post-analytical aspects of PD-L1 IHC testing, including specimen type, validation of assays, external quality assurance and training.
PMID: 31870882
ISSN: 1556-1380
CID: 4244102
Kappa-on-Heavy (KoH) bodies are a distinct class of fully-human antibody-like therapeutic agents with antigen-binding properties
Macdonald, Lynn E; Meagher, Karoline A; Franklin, Matthew C; Levenkova, Natasha; Hansen, Johanna; Badithe, Ashok T; Zhong, Maggie; Krueger, Pamela; Rafique, Ashique; Tu, Naxin; Shevchuk, James; Wadhwa, Saurabh; Ehrlich, George; Bautista, Joannie; Grant, Craig; Esau, Lakeisha; Poueymirou, William T; Auerbach, Wojtek; Morton, Lori; Babb, Robert; Chen, Gang; Huang, Tammy; MacDonald, Douglas; Graham, Kenneth; Gurer, Cagan; Voronina, Vera A; McWhirter, John R; Guo, Chunguang; Yancopoulos, George D; Murphy, Andrew J
We describe a Kappa-on-Heavy (KoH) mouse that produces a class of highly diverse, fully human, antibody-like agents. This mouse was made by replacing the germline variable sequences of both the Ig heavy-chain (IgH) and Ig kappa (IgK) loci with the human IgK germline variable sequences, producing antibody-like molecules with an antigen binding site made up of 2 kappa variable domains. These molecules, named KoH bodies, structurally mimic naturally existing Bence-Jones light-chain dimers in their variable domains and remain wild-type in their antibody constant domains. Unlike artificially diversified, nonimmunoglobulin alternative scaffolds (e.g., DARPins), KoH bodies consist of a configuration of normal Ig scaffolds that undergo natural diversification in B cells. Monoclonal KoH bodies have properties similar to those of conventional antibodies but exhibit an enhanced ability to bind small molecules such as the endogenous cardiotonic steroid marinobufagenin (MBG) and nicotine. A comparison of crystal structures of MBG bound to a KoH Fab versus a conventional Fab showed that the KoH body has a much deeper binding pocket, allowing MBG to be held 4 Ã… further down into the combining site between the 2 variable domains.
PMID: 31879340
ISSN: 1091-6490
CID: 4250852
Levels of early-childhood behavioral inhibition predict distinct neurodevelopmental pathways to pediatric anxiety
Abend, Rany; Swetlitz, Caroline; White, Lauren K; Shechner, Tomer; Bar-Haim, Yair; Filippi, Courtney; Kircanski, Katharina; Haller, Simone P; Benson, Brenda E; Chen, Gang; Leibenluft, Ellen; Fox, Nathan A; Pine, Daniel S
BACKGROUND:Anxiety symptoms gradually emerge during childhood and adolescence. Individual differences in behavioral inhibition (BI), an early-childhood temperament, may shape developmental paths through which these symptoms arise. Cross-sectional research suggests that level of early-childhood BI moderates associations between later anxiety symptoms and threat-related amygdala-prefrontal cortex (PFC) circuitry function. However, no study has characterized these associations longitudinally. Here, we tested whether level of early-childhood BI predicts distinct evolving associations between amygdala-PFC function and anxiety symptoms across development. METHODS:Eighty-seven children previously assessed for BI level in early childhood provided data at ages 10 and/or 13 years, consisting of assessments of anxiety and an fMRI-based dot-probe task (including threat, happy, and neutral stimuli). Using linear-mixed-effects models, we investigated longitudinal changes in associations between anxiety symptoms and threat-related amygdala-PFC connectivity, as a function of early-childhood BI. RESULTS:In children with a history of high early-childhood BI, anxiety symptoms became, with age, more negatively associated with right amygdala-left dorsolateral-PFC connectivity when attention was to be maintained on threat. In contrast, with age, low-BI children showed an increasingly positive anxiety-connectivity association during the same task condition. Behaviorally, at age 10, anxiety symptoms did not relate to fluctuations in attention bias (attention bias variability, ABV) in either group; by age 13, low-BI children showed a negative anxiety-ABV association, whereas high-BI children showed a positive anxiety-ABV association. CONCLUSIONS:Early-childhood BI levels predict distinct neurodevelopmental pathways to pediatric anxiety symptoms. These pathways involve distinct relations among brain function, behavior, and anxiety symptoms, which may inform diagnosis and treatment.
PMCID:7711072
PMID: 30616705
ISSN: 1469-8978
CID: 5364702
Correction: Heterotypic CAF-tumor spheroids promote early peritoneal metastatis of ovarian cancer
Gao, Qinglei; Yang, Zongyuan; Xu, Sen; Li, Xiaoting; Yang, Xin; Jin, Ping; Liu, Yi; Zhou, Xiaoshui; Zhang, Taoran; Gong, Cheng; Wei, Xiao; Liu, Dan; Sun, Chaoyang; Chen, Gang; Hu, Junbo; Meng, Li; Zhou, Jianfeng; Sawada, Kenjiro; Fruscio, Robert; Grunt, Thomas W; Wischhusen, Jörg; Vargas-Hernández, VÃctor Manuel; Pothuri, Bhavana; Coleman, Robert L
PMID: 31591188
ISSN: 1540-9538
CID: 4129442
P2.09-24 IASLC Global Survey for Pathologists on PD-L1 Testing for Non-Small Cell Lung Cancer [Meeting Abstract]
Mino-Kenudson, M; Redman, M; Hedger, J; Daigneault, J; Botling, J; Brambilla, E; Chen, G; Chou, T; Cooper, W; Hirsch, F R; Jain, D; Kerr, K; Longshore, J; Lopez-Rios, F; Motoi, N; Pelosi, G; Tsao, M; Yatabe, Y; Beasley, M B; Borczuk, A; Bubendorf, L; Chung, J; Dacic, S; Hwang, D; Minami, Y; Moreira, A; Nicholson, A; Papotti, M; Poleri, C; Rekhtman, N; Roden, A C; Russell, P; Sholl, L; Thunnissen, E; Travis, W; Yoshida, A; Wynes, M; Wistuba, I; Lantuejoul, S
Background: PD-L1 immunohistochemistry (IHC) is now performed for advanced non-small cell lung cancer (NSCLC) patients to examine their eligibility for pembrolizumab treatment, as well as in Europe for durvalumab therapy after chemoradiation for stage III NSCLC patients. Four PD-L1 clinical trial validated assays (commercial assays) have been FDA/EMA approved or are in vitro diagnostic tests in multiple countries, but high running costs have limited their use; thus, many laboratories utilize laboratory-developed tests (LDTs). Overall, the PD-L1 testing seems to be diversely implemented across different countries as well as across different laboratories.
Method(s): The Immune biomarker working group of the IASLC international pathology panel conducted an international online survey for pathologists on PD-L1 IHC testing for NSCLC patients from 2/1/2019 to 5/31/2019. The goal of the survey was to assess the current prevalence and practice of the PD-L1 testing and to identify issues to improve the practice globally. The survey included more than 20 questions on pre-analytical, analytical and post-analytical aspects of the PDL1 IHC testing, including the availability/type of PD-L1 IHC assay(s) as well as the attendance at a training course(s) and participation in a quality assurance program(s).
Result(s): 344 pathologists from 310 institutions in 64 countries participated in the survey. Of those, 38% were from Europe (France 13%), 23% from North America (US 17%) and 17% from Asia. 53% practice thoracic pathology and 36%, cytopathology. 11 pathologists from 10 countries do not perform PD-L1 IHC and 7.6% send out to outside facility. Cell blocks are used by 75% of the participants and cytology smear by 9.9% along with biopsies and surgical specimens. Pre-analytical conditions are not recorded in 45% of the institutions. Clone 22C3 is the most frequently used (61.5%) (59% with the commercial assay; 41% with LDT) followed by clone SP263 (45%) (71% with the commercial assay; 29% with LDT). Overall, one or several LDTs are used by 57% of the participants. A half of the participants reported turnaround time as 2 days or less, while 13% reported it as 5 days or more. Importantly, 20% of the participants reported no quality assessment, 15%, no formal training session for PD-L1interpretation and 14%, no standardized reporting system.
Conclusion(s): There is marked heterogeneity in PD-L1 testing practice across individual laboratories. In addition, the significant minority reported a lack of quality assurance, formal training and/or standardized reporting system that need to be established to improve the PD-L1 testing practice globally. Keywords: global survey, NSCLC, PD-L1 immunohistochemistry
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EMBASE:2003407348
ISSN: 1556-1380
CID: 4152042
