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Oral Scutellarin Treatment Ameliorates Retinal Thinning and Visual Deficits in Experimental Glaucoma
Zhu, Jingyuan; Sainulabdeen, Anoop; Akers, Krystal; Adi, Vishnu; Sims, Jeffrey R; Yarsky, Eva; Yan, Yi; Yu, Yu; Ishikawa, Hiroshi; Leung, Christopher K; Wollstein, Gadi; Schuman, Joel S; Wei, Wenbin; Chan, Kevin C
PMCID:8369066
PMID: 34414202
ISSN: 2296-858x
CID: 4988952
Diffusion Kurtosis Imaging Reveals Optic Tract Damage That Correlates with Clinical Severity in Glaucoma
Sun, Zhe; Parra, Carlos; Bang, Ji Won; Fieremans, Els; Wollstein, Gadi; Schuman, Joel S; Chan, Kevin C
Glaucoma is a neurodegenerative disease of the visual system and is the leading cause of irreversible blindness worldwide. To date, its pathophysiological mechanisms remain unclear. This study evaluated the feasibility of advanced diffusion magnetic resonance imaging techniques for examining the microstructural environment of the visual pathway in glaucoma. While conventional diffusion tensor imaging (DTI) showed lower fractional anisotropy and higher directional diffusivities in the optic tracts of glaucoma patients than healthy controls, diffusion kurtosis imaging (DKI) and the extended white matter tract integrity (WMTI) model indicated lower radial kurtosis, higher axial and radial diffusivities in the extra-axonal space, lower axonal water fraction, and lower tortuosity in the same regions in glaucoma patients. These findings suggest glial involvements apart from compromised axonal integrity in glaucoma. In addition, DKI and WMTI but not DTI parameters significantly correlated with clinical ophthalmic measures via optical coherence tomography and visual field perimetry testing. Taken together, DKI and WMTI provided sensitive and comprehensive imaging biomarkers for quantifying glaucomatous damage in the white matter tract across clinical severity complementary to DTI.
PMCID:8163524
PMID: 33018335
ISSN: 2694-0604
CID: 4898522
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; Sousa, Andre S; Gabriel, Andre; Schmidt, André; Lundeen, Andrea M; Bartykowszki, Andrea; Lorimer, Andrea; Mortara, Andrea; Pascual, Andrea; Coelho, Andreia; Rocha, Andreia; GarcÃa-Rincón, Andrés; Howarth, Andrew G; Moriarty, Andrew J; Docherty, Andrew; Starovoytov, Andrew; Zurick, Andrew; Åabyk, Andrzej; Swiatkowski, Andrzej; Lam, Andy; Kawakami, Anelise; Hoye, Angela; Kim, Angela; Smit, Angelique; Nobre, Angelo; Shah, Anil V; Ljubez, Anja; Anand, Anjali; Sachdeva, Ankush; Greenberg, Ann; Luyten, Ann; Ostrander, Ann; Di Donato, Anna; Cichocka-Radwan, Anna; Fojt, Anna; Plachcinska, Anna; Proietti, Anna; Teresinska, Anna; Webb, Anne Marie; Cartwright, Anne; Heath, Anne; Mackin, Anne; Amaritakomol, Anong; Chaiyasri, Anong; Chauhan, Anoop; Mathew, Anoop; Gemignani, Anthony; Andres, Anto Luigi; Vega, Antonia; Hansen, Antonietta; Iglesias, Antonino Ginel; Carvalho, Antonio Carlos; Di Chiara, Antonio; Serra Peñaranda, Antonio; Carvalho, Antonio; Colombo, Antonio; Fiarresga, Antonio; Rao, Anupama; 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; Stournaras, Dimitrios; Patel, Dipti; Li, Dongze; Exley, Donna; Grahl, Dorit; Stanojevic, Dragana; Cacela, Duarte; Conway, Dwayne S G; Bermudez, E Pinar; Punnoose, Eapen; Tay, Edgar L; Karanjah, Edgar; Verna, Edoardo; Hernandez-Rangel, Eduardo; Nicol, Edward D; McFalls, Edward O; Martin, Edward T; Kaczmarska, Edyta; Lubinskaya, Ekaterina I; Demchenko, Elena A; Refoyo Salicio, Elena; Feen, Eli; Durán-Cortés, Elihú; Janzen, Elisabeth M; Hannemann, Elise L; Dongen, Elise van; Piloto, Elissa Restelli; Kaplan, Eliza; Srbinovska Kostovska, Elizabeta; Capasso-Gulve, Elizabeth; Congdon, Elizabeth; Ferguson, Elizabeth; Zbyshevskaya, Elizaveta V; Magedanz, Ellen; Fridell, Ellie; Lader, Ellis W; Kedhi, Elvin; Racca, Emanuela; Tachot, Emilie; DeRosa, Emily; Alonso-Ãlvarez, Encarnación; Nicollet, Eric; Peterson, Eric; Rosas, Erick Alexánderson; Morales, Erick Donato; Orvis, Erin; Moga, Ermina; Montpetit, Estelle; Figueiredo, Estevao; Passamani, Eugene; Nikolsky, Eugenia; Yeoh, Eunice; Kretov, Evgeniy I; 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; Gulati, Gurpreet; Pucci, Gustavo; Abd Hadi, Hafidz; Zhang, Haibo; Wang, Haitao; Marciniak, Halina; Chen, Han; Kerr, Hanan; Najm, Hani; Douglas, Hanna; Phillips, Hannah; Dai, Hao; Dong, Haojian; Jamil, Haqeel; Sivadasanpillai, Harikrishnan; Suryapranata, Harry; Reda, Hassan; Pomeroy, Hayley; Barrentine, Heather; Golden, Heather; Hurlburt, Heather; Wilson, Heidi; Tucker, Helen C; Abergel, Helene; Siddaram, Hemalata; Osseni, Hermine; Schuchlenz, Herwig; Zeng, Hesong; Skali, Hicham; Solomon, Hilda; Horton, Hollie; Hetrick, Holly; Little, Holly; Park, Holly; Chi, Hongjie; Mahrous, Hossam; Levite, Howard A; Pejkov, Hristo; Li, Huajun; Bloise-Adames, Hugo; Marques, Hugo; Zhong, Hui; Zhang, Hui-Min; Hashim, Humayrah; Yeh, Hung-I; El Fishawy, Hussien; Webb, Ian; Kullo, Iftikhar; Grazhdankin, Igor O; Hamzeh, Ihab; Hassan, Ikraam; Ueda, Ikuko; Pina, Ileana L; Tamasauskiene, Ilona; Bouwhuis, Ilse; Arif, Imran; Wenzelburger, Ina; Zimbarra Cabrita, Inês; Rodrigues, Ines; Robbins, Inga H; Soveri, Inga; 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; 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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
Initial Invasive or Conservative Strategy for Stable Coronary Disease
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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; Stournaras, Dimitrios; Patel, Dipti; Li, Dongze; Exley, Donna; Grahl, Dorit; Stanojevic, Dragana; Cacela, Duarte; Conway, Dwayne S G; Bermudez, E Pinar; Punnoose, Eapen; Tay, Edgar L; Karanjah, Edgar; Verna, Edoardo; Hernandez-Rangel, Eduardo; Nicol, Edward D; McFalls, Edward O; Martin, Edward T; Kaczmarska, Edyta; Lubinskaya, Ekaterina I; Demchenko, Elena A; Refoyo Salicio, Elena; Feen, Eli; Durán-Cortés, Elihú; Janzen, Elisabeth M; Hannemann, Elise L; Dongen, Elise van; Piloto, Elissa Restelli; Kaplan, Eliza; Srbinovska Kostovska, Elizabeta; Capasso-Gulve, Elizabeth; Congdon, Elizabeth; Ferguson, Elizabeth; Zbyshevskaya, Elizaveta V; Magedanz, Ellen; Fridell, Ellie; Lader, Ellis W; Kedhi, Elvin; Racca, Emanuela; Tachot, Emilie; DeRosa, Emily; Alonso-Ãlvarez, Encarnación; Nicollet, Eric; Peterson, Eric; Rosas, Erick Alexánderson; Morales, Erick Donato; Orvis, Erin; Moga, Ermina; Montpetit, Estelle; Figueiredo, Estevao; Passamani, Eugene; Nikolsky, Eugenia; Yeoh, Eunice; Kretov, Evgeniy I; 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; Gulati, Gurpreet; Pucci, Gustavo; Abd Hadi, Hafidz; Zhang, Haibo; Wang, Haitao; Marciniak, Halina; Chen, Han; Kerr, Hanan; Najm, Hani; Douglas, Hanna; Phillips, Hannah; Dai, Hao; Dong, Haojian; Jamil, Haqeel; Sivadasanpillai, Harikrishnan; Suryapranata, Harry; Reda, Hassan; Pomeroy, Hayley; Barrentine, Heather; Golden, Heather; Hurlburt, Heather; Wilson, Heidi; Tucker, Helen C; Abergel, Helene; Siddaram, Hemalata; Osseni, Hermine; Schuchlenz, Herwig; Zeng, Hesong; Skali, Hicham; Solomon, Hilda; Horton, Hollie; Hetrick, Holly; Little, Holly; Park, Holly; Chi, Hongjie; Mahrous, Hossam; Levite, Howard A; Pejkov, Hristo; Li, Huajun; Bloise-Adames, Hugo; Marques, Hugo; Zhong, Hui; Zhang, Hui-Min; Hashim, Humayrah; Yeh, Hung-I; El Fishawy, Hussien; Webb, Ian; Kullo, Iftikhar; Grazhdankin, Igor O; Hamzeh, Ihab; Hassan, Ikraam; Ueda, Ikuko; Pina, Ileana L; Tamasauskiene, Ilona; Bouwhuis, Ilse; Arif, Imran; Wenzelburger, Ina; Zimbarra Cabrita, Inês; Rodrigues, Ines; Robbins, Inga H; Soveri, Inga; 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: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
Quantitative imaging of the clearance systems in the eye and the brain [Editorial]
Deng, Wenyu; Liu, Crystal; Parra, Carlos; Sims, Jeffrey R; Faiq, Muneeb A; Sainulabdeen, Anoop; Song, Hana; Chan, Kevin C
PMCID:6960420
PMID: 31956524
ISSN: 2223-4292
CID: 4269542
Widespread brain reorganization perturbs visuomotor coordination in early glaucoma
Trivedi, Vivek; Bang, Ji Won; Parra, Carlos; Colbert, Max K; O'Connell, Caitlin; Arshad, Ahmel; Faiq, Muneeb A; Conner, Ian P; Redfern, Mark S; Wollstein, Gadi; Schuman, Joel S; Cham, Rakie; Chan, Kevin C
Glaucoma is the world's leading cause of irreversible blindness, and falls are a major public health concern in glaucoma patients. Although recent evidence suggests the involvements of the brain toward advanced glaucoma stages, the early brain changes and their clinical and behavioral consequences remain poorly described. This study aims to determine how glaucoma may impair the brain structurally and functionally within and beyond the visual pathway in the early stages, and whether these changes can explain visuomotor impairments in glaucoma. Using multi-parametric magnetic resonance imaging, glaucoma patients presented compromised white matter integrity along the central visual pathway and around the supramarginal gyrus, as well as reduced functional connectivity between the supramarginal gyrus and the visual occipital and superior sensorimotor areas when compared to healthy controls. Furthermore, decreased functional connectivity between the supramarginal gyrus and the visual brain network may negatively impact postural control measured with dynamic posturography in glaucoma patients. Taken together, this study demonstrates that widespread structural and functional brain reorganization is taking place in areas associated with visuomotor coordination in early glaucoma. These results implicate an important central mechanism by which glaucoma patients may be susceptible to visual impairments and increased risk of falls.
PMID: 31578409
ISSN: 2045-2322
CID: 4116332
Intracameral Injection of a Chemically Cross-Linked Hydrogel to Study Chronic Neurodegeneration in Glaucoma
Chan, Kevin C; Yu, Yu; Han Ng, Shuk; Mak, Heather K; Yip, Yolanda W Y; van der Merwe, Yolandi; Ren, Tianmin; Yung, Jasmine S Y; Biswas, Sayantan; Cao, Xu; Chau, Ying; Leung, Christopher K S
Investigation of neurodegeneration in glaucoma, a leading cause of irreversible blindness worldwide, has been obfuscated by the lack of an efficient model that provides chronic, mild to moderate elevation of intraocular pressure (IOP) with preservation of optical media clarity for long term, in vivo interrogation of the structural and functional integrity of the retinal ganglion cells (RGCs). Here, we designed and formulated an injectable hydrogel based on in situ cross-linking of hyaluronic acid functionalized with vinylsulfone (HA-VS) and thiol groups (HA-SH). Intracameral injection of HA-VS and HA-SH in C57BL/6J mice exhibited mild to moderate elevation of IOP with daily mean IOP ranged between 14±3 and 24±3 mmHg, which led to progressive, regional loss of RGCs evaluated with in vivo, time-lapse, confocal scanning laser ophthalmoscopy; a reduction in fractional anisotropy in the optic nerve and the optic tract projected from the eye with increased IOP in diffusion tensor magnetic resonance imaging; a decrease in positive scotopic threshold response in electroretinography; and a decline in visual acuity measured with an optokinetic virtual reality system. The proportion of RGC loss was positively associated with the age of the animals, and the levels and the duration of IOP elevation. The new glaucoma model recapitulates key characteristics of human glaucoma which is pertinent to the development and pre-clinical testing of neuroprotective and neuroregenerative therapies. Statement of Significance A new model to study chronic neurodegeneration in glaucoma has been developed via intracameral injection of a specifically designed hyaluronic acid functionalized with vinylsulfone and thiol groups for cross-linking. Intracameral injection of the chemically cross-linked hydrogel generates mild to moderate IOP elevation, resulting in progressive degeneration of the retinal ganglion cells, optic nerve, and optic tract, and a decline in visual function. The model recapitulates the key features of neurodegeneration in human glaucoma, which will facilitate and expedite the development of neuroprotective and neuroregenerative therapies.
PMID: 31176841
ISSN: 1878-7568
CID: 3926752
Cholinergic nervous system and glaucoma: From basic science to clinical applications
Faiq, Muneeb A; Wollstein, Gadi; Schuman, Joel S; Chan, Kevin C
The cholinergic system has a crucial role to play in visual function. Although cholinergic drugs have been a focus of attention as glaucoma medications for reducing eye pressure, little is known about the potential modality for neuronal survival and/or enhancement in visual impairments. Citicoline, a naturally occurring compound and FDA approved dietary supplement, is a nootropic agent that is recently demonstrated to be effective in ameliorating ischemic stroke, traumatic brain injury, Parkinson's disease, Alzheimer's disease, cerebrovascular diseases, memory disorders and attention-deficit/hyperactivity disorder in both humans and animal models. The mechanisms of its action appear to be multifarious including (i) preservation of cardiolipin, sphingomyelin, arachidonic acid content of phosphatidylcholine and phosphatidylethanolamine, (ii) restoration of phosphatidylcholine, (iii) stimulation of glutathione synthesis, (iv) lowering glutamate concentrations and preventing glutamate excitotoxicity, (v) rescuing mitochondrial function thereby preventing oxidative damage and onset of neuronal apoptosis, (vi) synthesis of myelin leading to improvement in neuronal membrane integrity, (vii) improving acetylcholine synthesis and thereby reducing the effects of mental stress and (viii) preventing endothelial dysfunction. Such effects have vouched for citicoline as a neuroprotective, neurorestorative and neuroregenerative agent. Retinal ganglion cells are neurons with long myelinated axons which provide a strong rationale for citicoline use in visual pathway disorders. Since glaucoma is a form of neurodegeneration involving retinal ganglion cells, citicoline may help ameliorate glaucomatous damages in multiple facets. Additionally, trans-synaptic degeneration has been identified in humans and experimental models of glaucoma suggesting the cholinergic system as a new brain target for glaucoma management and therapy.
PMID: 31242454
ISSN: 1873-1635
CID: 3963732
In vivo imaging of structural, metabolic and functional brain changes in glaucoma
Kasi, Anisha; Faiq, Muneeb A; Chan, Kevin C
Glaucoma, the world's leading cause of irreversible blindness, is a condition for which elevated intraocular pressure is currently the only modifiable risk factor. However, the disorder can continue to progress even at reduced intraocular pressure. This indicates additional key factors that contribute to the etiopathogenesis. There has been a growing amount of literature suggesting glaucoma as a neurodegenerative disease of the visual system. However, it remains debatable whether the observed pathophysiological conditions are causes or consequences. This review summarizes recent in vivo imaging studies that helped advance the understanding of early glaucoma involvements and disease progression in the brains of humans and experimental animal models. In particular, we focused on the non-invasive detection of early structural and functional brain changes before substantial clinical visual field loss in glaucoma patients; the eye-brain interactions across disease severity; the metabolic changes occurring in the brain's visual system in glaucoma; and, the widespread brain involvements beyond the visual pathway as well as the potential behavioral relevance. If the mechanisms of glaucomatous brain changes are reliably identified, novel neurotherapeutics that target parameters beyond intraocular pressure lowering can be the promise of the near future, which would lead to reduced prevalence of this irreversible but preventable disease.
PMCID:6334611
PMID: 30539811
ISSN: 1673-5374
CID: 4113482
Widespread Structural and Functional Brain Connectivity Changes and Associations with Balance in Glaucoma [Meeting Abstract]
Bang, Ji Won; Trivedi, Vivek; Parra, Carlos; Colbert, Max; O\Connel, Caitlin; Faiq, Muneeb A.; Conner, Ian; Redfern, Mark; Wollstein, Gadi; Schuman, Joel S.; Cham, Rakie; Chan, Kevin C.
ISI:000488800701112
ISSN: 0146-0404
CID: 4154432
