101 results on '"Itamoto, K."'
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2. Edoxaban versus warfarin in patients with atrial fibrillation
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Robert P. Giugliano, Christian T. Ruff, Eugene Braunwald, Sabina A. Murphy, Stephen D. Wiviott, Jonathan L. Halperin, Albert L. Waldo, Michael D. Ezekowitz, Jeffrey I. Weitz, Jind?ich ?pinar, Witold Ruzyllo, Mikhail Ruda, Yukihiro Koretsune, Joshua Betcher, Minggao Shi, Laura T. Grip, Shirali P. Patel, Indravadan Patel, James J. Hanyok, Michele Mercuri, Elliott M. Antman, Braunwald E, Antman EM, Giugliano RP, Ruff CT, Morin SE, Hoffman EB, Murphy SA, Deenadayalu N, Grip L, Mercuri M, Lanz H, Patel I, Curt V, Duggal A, Hanyok J, Davé J, Morgan D, Choi Y, Shi M, Jin J, Xie J, Crerand W, Kappelhof J, Maxwell W, Skinner M, Patel S, Betcher J, Selicato G, Otto C. Jr, Reissner C, Smith K, Ostroske J, Ron A, Giugliano R, Connolly S, Camm J, Ezekowitz M, Halperin J, Waldo A, Paolasso E, Aylward P, Heidbuchel H, Nicolau JC, Goudev A, Roy D, Weitz J, Corbalán R, Yang Y, Botero R, Bergovec M, Ŝpinar J, Grande P, Hassager C, Voitk J, Huikuri H, Nieminen M, Blanc JJ, LeHeuzey JY, Mitrovic V, Alexopoulos D, Sotomora G, Kiss R, SomaRaju B, Lewis B, Merlini P, Metra M, Koretsune Y, Yamashita T, García Castillo A, Ophuis T, White H, Atar D, Horna M, Babilonia N, Ruzyllo W, Morais J, Dorobantu M, Ruda M, Ostojic M, Duris T, Dalby A, Chung N, Zamorano JL, Juul Möller S, Moccetti T, Chen SA, Sritara P, Oto A, Parkhomenko A, Senior R, Verheugt F, Skene A, Anderson J, Bauer K, Easton JD, Goto S, Wiviott S, Lowe C, Awtry E, Berger CJ, Croce K, Desai A, Gelfand E, Goessling W, Greenberger NJ, Ho C, Leeman DE, Link MS, Norden AD, Pande A, Rost N, Ruberg F, Silverman S, Singhal A, Vita JA, Vogelmann O, Gonzalez C, Ahuad Guerrero R, Rodriguez M, Albisu J, Rosales E, Allall O, Reguero M, Alvarez C, Garcia M, Ameriso S, Ameriso P, Amuchastegui M, Caceres M, Beloscar J, Petrucci J, Berli M, Budassi N, Valle M, Bustamante Labarta G, Saravia M, Caccavo A, Fracaro V, Cartasegna L, Novas V, Caruso O, Zarandon RS, Colombo H, Morandini M, Cuello J, Rosell M, Cuneo C, Bocanera M, D'Amico A, Cendali G, Dran R, Moreno V, Estol C, Davolos M, Facello A, Facello M, Falu E, Iriarte M, Femenia F, Arrieta M, Fuselli J, Zanotti A, Gant Lopez J, Meiller F, Garcia Duran R, Perlo D, Garrido M, Ceirano C, Giacomi G, Eden M, Giannaula R, Huerta M, Goicoechea R, von Wulffen M, Hominal M, Bianchini M, Jure H, Jure D, Kevorkian R, Monaco F, Lanternier G, Belcuore M, Liniado G, Iglesias M, Litvak B, Nigro A, Llanos J, Vignau S, Lorente C, Shatsky K, Lotti J, Raimondi G, Mackinnon I, Carne M, Manuale O, Calderon M, Marino J, Funes I, Muntaner J, Gandur H, Nul D, Verdini E, Piskorz D, Tommasi A, Povedano G, Casares E, Pozzer D, Fernandez E, Prado A, Venturini C, Ramos H, Navarrete S, Alvarez M, Sanchez A, Bowen L, Sanjurjo M, Codutti O, Saravia Toledo S, Formoso I, Schmidberg J, Goloboulicz A, Schygiel P, Buzzetti C, Severino P, Morara P, Sosa Liprandi M, Teves M, Vico M, Morell Y, Anderson C, Paraskevaidis T, Arstall M, Hoffmann B, Colquhoun D, Price Smith S, Crimmins D, Slattery A, Dart A, Kay S, Davis S, Silver G, Flecknoe Brown S, Roberts J, Gates P, Jones S, Lehman R, Morrison H, McKeirnan M, Li J, Paul V, Batta C, Purnell P, Perrett L, Szto G, O'Shea V, Capiau L, Banaeian F, De Bleecker J, de Koning K, De Tollenaere M, De Bruyne L, Desfontaines P, Tincani G, Meeusen K, Herzet J, Malmendier D, Mairesse G, Raepers M, Parqué J, Clinckemaille N, Scavée C, Huyberechts D, Stockman D, Jacobs C, Vandekerckhove Y, Derycker K, Vanwelden J, van Welden J, Vervoort G, Mestdagh I, Vrolix M, Beerts C, Wollaert B, Denie D, Amato Vincenzo de Paola A, Coutinho E, Andrade Lotufo P, de Melo RF, Atie J, Motta C, Augusto Alves da Costa F, Ferraz RF, Bertolim Precoma D, Sehnem E, Botelho R, Cunha S, Brondani R, Fleck N, Chaves Junior H, Silva J, Costantini C, Barroso D, De Patta M, Pereira V, Duda N, Laimer R, Dutra O, Morgado S, Faustino Saporito W, Seroqui M, Ferreira L, Araújo E, Finimundi H, Daitz C, Gagliardi R, Pereira G, Gomes M, Gomes A, Guimarães A, Ninho L, Jaeger C, Pereira L, Jorge J, Cury C, Kaiser S, Almeida A, Kalil C, Radaelli G, Kunz Sebba Barroso de Souza W, Morales K, Leaes P, Luiz RO, Pimenta Almeida J, Gozalo A, Reis G, Avellar K, Reis Katz Weiand L, Leipelt J, Rocha J, Barros R, Rodrigues L, Rocha MR, Rodrigues A, Rodrigues D, Rossi dos Santos F, Pagnan LG, Sampaio R, do Val R, Saraiva J, Vicente C, Simoes M, Carraro A, Sobral Filho D, Lustosa E, Villas Boas F, Almeida M, Zimmermann S, Zimmermann EB, Chompalova B, Parishev G, Denchev S, Milcheva N, Donova T, Gergova V, Georgiev B, Kostova E, Kinova E, Hergeldjieva V, Kamenova P, Manolova A, Vasilev I, Mihov A, Miteva B, Mincheva V, Stoyanovski V, Nikolov F, Vasilev D, Pencheva 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Ricci J, Bozek B, Rupka D, Marchand C, Shu D, Silverio G, St Hilaire R, Morissette A, Sussman J, Kailey P, Syan G, Bobbie C, Talajic M, David D, Talbot P, Tremblay M, Teitelbaum I, Teitelbaum J, Velthuysen G, Giesbrecht L, Wahby R, Morley A, Wharton S, Caterini T, Woodford T, Balboa W, Matus LR, Bugueño C, Mondaca PM, Cobos J, Obreque C, Corbalan R, Parada A, Florenzano F, Diaz PA, Lopetegui M, Rebolledo C, Manriquez L, Silva LM, Martinez D, Llamas RR, Opazo M, Pérez MC, Pincetti C, Carrasco GT, Potthoff S, Staub JZ, Campisto Y, Stockins B, Lara CL, Yovaniniz P, Azua MG, Bai F, Xu GL, Chen JZ, Xie XD, Chen XP, Zhang X, Dong YG, Feng C, Fu GS, Zhang P, Hong K, You ZG, Hong L, Qiu Y, Jiang XJ, Qu Z, Li L, Liu H, Li TF, Kong YQ, Li WM, Liu B, Li ZQ, Liu Y, Liao DN, Gu XJ, Liu L, Lu ZH, Ma SM, Yang ZY, Wang DM, Qi SY, Wang GP, Shi XJ, Wei M, Huang D, Wu SL, Li YE, Xu JH, Gu JY, Xu YM, Liang YZ, Yang K, Li AY, Yang YJ, Zheng X, Zheng Y, Gao M, Yin YH, Xu YP, Yu B, Li LL, Yuan ZY, Qiang H, Zhang HQ, Lin YN, Zhang Z, Kang H, Zhao RP, Han RJ, Zhao XL, Wang JQ, Zheng ZQ, Li BG, Zhou SX, Zhang YL, Accini J, Accini M, Cano N, Pineda LL, Delgado Restrepo J, Arroyave C, Fernández Ruiz R, Diaz IA, Hernandez H, Delgado P, Jaramillo Muñoz C, Builes A, Manzur F, Rodriguez ER, Moncada Corredor M, Giraldo DL, Orozco Linares L, Fonseca J, Quintero A, Gonzales C, Sanchez Vallejo G, Mejia IP, Bagatin J, Carevic V, Car S, Jeric M, Ciglenecki N, Tusek S, Ferri Certic J, Romic I, Francetic I, Ausperger KM, Jelic V, Jurinjak SJ, Knezevic A, Buksa B, Samardzic P, Lukenda KC, Steiner R, Kirner D, Sutalo K, Bakliza Z, Vrazic H, Lucijanic T, Bar M, Brodova P, Berka L, Kunkelova V, Brtko M, Burianova H, Cermak O, Elbl L, Ferkl R, Florian J, Francek L, Golan L, Gregor P, Honkova M, Hubac J, Jandik J, Jarkovsky P, Jelinek Z, Jerabek O, Jirmar R, Kobza R, Kochrt M, Kostkova G, Kosek Z, Kovar P, Kuchar R, Kvasnicka J, Ludka O, Machova V, Krocova E, Melichar M, Nechanicky R, Olsr J, Peterka K, Petrova I, Havlova I, Pisova J, Podrazil P, Jirsova E, Reichert P, Slaby J, Spacek R, Spinar J, Labrova R, Vodnansky P, Samkova D, Zidkova E, Dodt K, Christensen H, Christensen L, Loof A, Ibsen H, Madsen H, Iversen H, Veng Olsen T, Nielsen H, Olsen R, Overgaard K, Petrovic V, Raymond I, Raae D, Sand N, Svenningsen A, Torp Pedersen C, Jakobsen U, Wiggers H, Serup Hansen K, Kaik J, Stern A, Kolk R, Laane E, Rivis L, Paumets M, Laheäär M, Rosenthal A, Rajasalu R, Vahula V, Ratnik E, Kaarleenkaski S, Hussi E, Valpas S, Jäkälä P, Lappalainen T, Mäenpää A, Viitaniemi J, Nyman K, Sankari T, Rasi H, Salminen O, Virtanen V, Nappila H, Le Heuzey J, Agraou B, El Jarroudi F, Amarenco P, Boursin P, Babuty D, Boyer M, Belhassane A, Berbari H, Blanc J, Dias P, Coisne D, Berger N, Decoulx E, El Jarroudi M, Dinanian S, Arfaoui M, Hermida J, Deruche E, Kacet S, Corbut S, Poulard J, Leparree S, Roudaut R, Duprat C, Al Zoebi A, Wurow A, Bernhardt P, Dichristin U, Berrouschot J, Vierbeck S, Beyer Westendorf J, Sehr B, Bouzo M, Schnelzer P, Braun R, Ladenburger K, Buhr M, Weihrauch D, Contzen C, Kara M, Daut W, Ayasse D, Degtyareva E, Kranz P, Drescher T, Herfurth B, Faghih M, Forck Boedeker K, Schneider K, Fuchs R, Manuela W, Grigat C, Otto A, Hartmann A, Peitz M, Heuer H, Dieckheuer U, Hoffmann U, Dorn S, Hoffmann S, Schuppe M, Horacek T, Fink P, Junggeburth J, Schmid S, Jungmair W, Schoen B, Kleinecke Pohl U, Meusel P, Koenig H, Bauch F, Lohrbaecher Kozak I, Grosse B, Lueders S, Venneklaas U, Luttermann M, Wulf M, Maus O, Hoefer K, Meissner G, Braemer U, Meyer Pannwitt U, Frahm E, Vogt S, Muegge A, Barbera S, Mueller Glamann M, Raddatz K, Piechatzek R, Lewinsky D, Pohl W, Proskynitopoulos N, Kuhlmann M, Rack K, Pilipenko H, Rinke A, Kühlenborg A, Schaefer A, Szymanowski N, Schellong S, Frommhold R, Schenkenberger I, Finsterbusch T, Dreykluft K, Schiewe C, Schmidt A, Schmidt M, Schreckenberg A, Hellmers J, Seibert H, Gold G, Sohn H, Baylacher M, Spitzer S, Bonin K, Stoehring R, Taggeselle J, Zarpentin C, Veltkamp R, Ludwig I, Voehringer, Buchholz M, Weyland K, Winkelmann B, Buelow Johansen B, Wolde C, Winter K, Mavronasiou E, Bourlios P, Tziortziotis A, Karamitsos C, Exarchou E, Kifnidis K, Daskalaki A, Moschos N, Dimitra K, Olympios C, Kartsagkoulis E, Pyrgakis V, Korantanis K, Ayau Milla O, Ramirez Vde L, Guzman Melgar I, Jimenez T, Ovando Lavagnino A, Guevara S, Rodas Estrada M, Sanchez M, Pozuelos JM, Sanchez Samayoa C, Guerra L, Velasquez Camas L, Almaraz SP, Dioszeghy P, Muskoczki E, Edes I, Szatmari J, Fiok J, Varga A, Kanakaridisz N, Kosztyu M, Kis E, Feil JF, Jakal A, Koczka M, Kovacs I, Baranyai M, Kovacs Z, Lupkovics G, Karakai HH, Matoltsy A, Kiss T, Medvegy M, Kiss K, Merkely B, Kolumban E, Nagy A, Palinkas A, Toth SR, Sayour A, Bognar A, Simor T, Ruzsa D, Sipos T, Szakal I, Tomcsanyi J, Marosi A, Vertes A, Kincses M, Malhan S, Abdullakutty J, Agarwal D, Ranka R, Arneja J, Memon A, Arora V, Shree R, Avvaru G, Shaikh A, Babu P, Rao B, Babu R, Reddy J, Banker D, Sheth T, Benjarge P, Surushe S, Bharani A, Solanki R, Bhargava V, Rathi A, Biniwale A, Bhuti M, Calambur N, Somaraju B, Karnwal N, Chopda M, Mali N, Goyal N, Saini A, Gupta J, Singh P, Hadan S, Savanth P, Hardas S, Thakor G, Hiremath J, Ghume A, Jain R, Pahuja M, Joseph S, Oommen D, Joseph J, Thomas R, Joshi H, Iby, Kale V, Raut N, Kandekar B, Kandekar S, Kishore R, Krishnan H, Kotiwale V, Kulkarni R, Deokar M, Kulkarni G, Lawande A, Kumar P, Karpuram M, Kumar A, Francis J, Kumbla M, Anthony A, Lavhe P, Kale M, Mardikar H, Bhaskarwar P, Mathur A, Sharma P, Menon J, Francis V, Namjoshi D, Shelke S, Narendra J, Natarajan S, Oomaan A, Gurusamy P, Angel J, Purayil MP, Shams S, Pandurangi U, Sababathi R, Parekh P, Jasani B, Patki N, Babbar A, Pinto B, Kharalkar H, Premchand R, Jambula H, Rao M, Vuriya A, Ravi Shankar A, Reddy R, Bekal S, Barai A, Saha D, Gadepalli R, Sant H, Jadhav D, Sarna M, Arora T, Sawhney J, Singh R, Sethi K, Bansal N, Sethia A, Sethia S, Shetty G, Sudheer R, Singh G, Gupta R, Srinivas A, Thankaraj L, Varma S, Kaur A, Vinod MV, Thakur B, Zanwar I, Dharmarao A, Atar S, Lasri E, Dicker D, Marcoviciu D, Elias M, Ron GA, Francis A, Ghantous R, Goldhaber A, Goldhaber M, Gottlieb S, Rouwaida S, Grossman E, Dagan T, Hasin Y, Roshrosh M, Hayek T, Majdoub A, Klainman E, Genin I, Lahav M, Gilat T, Ben Ari M, Lishner M, Karny M, Ouzan E, Givoni H, Rozenman Y, Logvinenko S, Schiff E, Sterlin J, Shochat M, Aloni I, Swissa M, Belatsky V, Tsalihin D, Kisos D, Zeltser D, Platner N, Berni A, Giovannelli F, Boriani G, Cervi E, Comi G, Peruzzotti L, Cuccia C, Forgione C, De Caterina R, De Pace D, De Servi S, Mariani M, Di Lenarda A, Mazzone C, Di Pasquale G, Di Niro M, Fattore L, Bosco B, Grassia V, Murena E, Laffi, Gaggioli G, Lo Pinto G, Raggi F, Marino P, Francalacci G, Babbolin M, Bulgari M, Penco M, Lioy E, Marciano C, Pirelli S, Paradiso G, Piseddu G, Fenu L, Raisaro A, Granzow K, Rasura M, Cannoni S, Severi S, Breschi M, Toschi V, Gagliano M, Zacà V, Furiozzi F, Hirahara T, Akihisa U, Masaki W, Ajioka M, Matsushita C, Anzai T, Mino K, Arakawa S, Tsukimine A, Endo H, Fujiwara M, Fujii K, Kozeni S, Fujii E, Kotera M, Fujimoto S, Omae K, Fujimoto K, Ichishita Y, Fujita T, Ito Y, Fukamizu S, Harada J, Fukuda N, Fujimoto C, Funazaki T, Yamaguchi A, Furukawa Y, Kamitake C, Hagiwara N, Naganuma M, Hara S, Kumagai S, Harada K, Fuki Y, Haruna T, Nakahara Y, Hashimoto Y, Shimazu Y, Hiasa Y, Oga Y, Higashikata T, Nakagawa Y, Hirayama A, Kawaguchi A, Iesaka Y, Miyamoto C, Iijima T, Higuchi K, Ino H, Noguchi H, Inomata T, Nakamura K, Ishibashi Y, Nozaki T, Ishii Y, Tomita H, Ishimaru S, Ise M, Itamoto K, Ito T, Onishi M, Iwade K, Sakuma Y, Iwasaki T, Nagatome H, Kakinoki S, Adachi C, Kamakura S, Nakahara F, Kamijo M, Iida S, Kamiyama K, Fujii R, Kato K, Ishida A, Kazatani Y, Ichikawa Y, Kitazawa H, Igarashi C, Kobayashi Y, Kikuchi R, Kohno M, Tamura S, Yumoto I, Kurabayashi M, Koya E, Masuyama T, Kaneno Y, Matsuda K, Ebina E, Meno H, Satake M, Mita T, Takeda M, Miyamoto N, Kimizu T, Miyauchi Y, Sakamoto S, Munemasa M, Murata J, Nagai Y, Sakata Y, Naito S, Oyama H, Nishi Y, Nagase T, Ochiai J, Junko H, Ogawa T, Sugeno M, Oguro H, Tanabe M, Okada K, Moriyama Y, Okajima K, Nakashima M, Okazaki O, Wada H, Okishige K, Kitani S, Okumura K, Narita Y, Onaka H, Moriyama H, Ozaki Y, Tanikawa I, Sakagami S, Nakano A, Sakuragi S, Hayashi N, Sakurai S, Ooki H, Sasaki T, Oosawa N, Satoh A, Fujimoto E, Seino Y, Narumi M, Shirai T, Shigenari M, Shoji Y, Ueda J, Sugi K, Miyazaki E, Sumii K, Asakura H, Takagi M, Mohri S, Takahashi W, Yoshida K, Takahashi A, Kishi N, Takahashi T, Sakurai Y, Takeda K, Yahata A, Takenaka T, Yamagishi K, Takeuchi S, Watanabe E, Tanaka K, Uchida M, Tanouchi J, Nishiya Y, Tsuboi H, Tsuboi N, Terakura K, Uematsu M, Yasumoto S, Ueyama Y, Usuda K, Sakai Y, Yagi M, Sato A, Yagi H, Kuroda T, Yamabe H, Sakamoto Y, Yamada T, Yamano R, Yamagishi T, Sasaki S, Yamamoto Y, Yamashina A, Takiguchi M, Yonehara T, Yoshino H, Nomura H, Yoshioka K, Fujiwara Y, Bayram Llamas E, Hurtado A, Calvo Vargas C, Limon MC, Cardona Muñoz E, Hernandez S, Carrillo J, Delgadillo T, Cásares Ramirez M, Valles JF, Garcia N, Colin MA, Garcia Castillo A, Jaramillo A, Leiva Pons J, de la Mora S, Llamas Esperón G, Grajales A, Mendez Machado G, Avila H, Ruiz LN, Magallanes G, Sánchez Díaz C, Ortiz A, Sánchez RV, Velazquez EM, Alhakim M, van Welsen I, Bruning T, Jones A, Buiks C, de Groot J, Radder I, de Vos R, Hazeleger R, Daniels R, Kietselaer B, Muijs L, Mannaerts H, Kooiman E, Mevissen H, van der Heijden D, Hofmeyer H, Anscombe R, O'Meeghan T, Kjentjes M, Benatar J, Borthwick L, Doughty R, Copley M, Fisher R, Monkley R, Green B, Scott D, Hamer A, Tomlinson J, Hart H, Turner A, Cammell R, Troughton R, Skelton L, Young C, Kennett K, Claussen H, Hofsøy K, Melbue R, Sandvik J, Thunhaug H, Tveit A, Enger S, Bustamante G, Guillen MT, Cabrera J, Mendoza RE, Chavez C, Luna C, Lema J, Carrion A, Llerena N, Bedregal SA, Medina Palomino F, Rodriguez J, Minchola J, Bautista C, Negron Miguel S, Armas BH, Rodriguez A, Romero N, Torres P, Rodriguez KF, Yanac Chavez P, Delgado S, Sambaz CM, Barcinas R, Zapanta M, Coching R, Vallenas M, Matiga G, Enad C, Rogelio G, Joaquin F, Roxas A. Jr, Gilo L, To R, Aquino M, Villamor L, Nario K, Adamus J, Korzeniowska Adamus J, Baszak J, Bronisz M, Cieslak B, Busz Papiez B, Krzystolik A, Cymerman K, Dabrowska M, Ptak A, Derlaga B, Laskowska Derlaga E, Domanska E, Guziewicz M, Gieroba A, Zajac E, Gniot J, Mroczkowski P, Januszewicz A, Makowiecka Ciesla M, Jazwinska Tarnawska E, Ciezak P, Jurowiecki J, Kaczmarek B, Pacholska A, Kaminski L, Kania G, Tymendorf K, Karczmarczyk A, Kaliszczak R, Konieczny M, Benicka E, Korzeniak R, Borowski W, Krzyzanowski W, Muzyk Osikowicz M, Kus W, Lesnik J, Wierzykowski T, Lewczuk J, Stopyra Poczatek M, Lubinski A, Szymanska K, Lysek R, Jaguszewska G, Matyszczak Toniak L, Sznajder R, Wnetrzak Michalska R, Kosmaczewska A, Mazur S, Chmielowski A, Miekus P, Kosmalska K, Mosiewicz J, Myslinski W, Napora P, Biniek D, Nessler J, Nessler B, Niezgoda K, Nej A, Nowak J, Olszewski M, Podjacka D, Janczewska D, Pogorzelska H, Polaszewska Pulkownik V, Bojanowska E, Raczak G, Zienciuk Krajka A, Rewinska H, 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Pazier P, Riofrio K, Braun D, Robinson J, Cherrico M, Roehll W, Hollihan P, Rosado, Barnhorst M, Rosado J, Bamhorst M, Rosen R, Martin C, Ross S, Freeman R, Ruoff G, Nelson T, Sacco J, Ball E, Samal A, Schomburg J, Sandberg J, Lafave J, Savin V, Clifton R, Schaefer S, Fekete A, Schneider R, Schneider W, Schulman D, Mercer S, Seals A, Ullig T, Holt A, Seide H, Mather N, Shah G, Witt P, Shalaby A, Seese M, Shanes J, Fleets J, Shaoulian E, Hren A, Sheikh K, Hengerer T, Shih H, Browning J, Shoukfeh M, Stephenson L, Siler T, Champagne M, Simpson P, Meyer R, Singh N, Turner K, Singh V, Nelson M, Skierka R, Hughes B, Keene R, Smith R, Hodnett P, Spangenthal S, Thomason L, Sperling M, Vasquez E, Spivack E, McCartney P, Staniloae C, Liu M, Steljes A, Cox C, Struble R, Vittitow T, Suresh D, Frost J, Swerchowsky V, Freemyer D, Szulawski I, Herwehe S, Tahirkheli N, Springer K, Takata T, Bruton T, Talano J, Leo L, Tami L, Corchado D, Tatarko M, Swauger M, Tawney K, Dastoli K, Teague S, Young K, Tee H, Mitchell T, Teixeira J, Southam D, Torres M, Tucker P, Salas L, Updegrove J, Hanna K, Val Mejias J, Harrelson KG, Vemireddy D, Cardoza T, Verma S, Parsons T, Vicari R, Warren K, Vijay N, Washam M, Vossler M, Kilcup S, Walsh R, Renaud K, Ward S, Locklear T, Waxman F, Sanchez G, Weiss R, St Laurent B, Westcott J, Williams D, Gibson C, Williams R, Dowling C, Willis J, VonGerichten S, Wood K, Capasso Gulve E, Worley S, Pointer S, Yarows S, Sheehan T, Yasin M, Yi J, Dongas B, Yousuf K, Zakhary B, Curtis S, Zeig S, Mason T, Zellner C, Harden M, Roper E, Waseem M, Grammer M., PERRONE FILARDI, PASQUALE, Cardiovascular Division (SZG), Brigham and Women's Hospital [Boston], Mount Sinai Medical Center, Icahn School of Medicine at Mount Sinai [New York] (MSSM), University Hospitals Case Medical Center (CLEVELAND - UHCMC), University Hospitals Case Medical Center, Jefferson Medical College (JMC), Thomas Jefferson University Hospitals, Thrombosis and Atherosclerosis Research Institute (TARI), McMaster University [Hamilton, Ontario], University Hospital Brno, Institute of Cardiology (WARSAW - Cardiology), Institute of Cardiology, Cardiology Research Center (MOSCOU - CRC), Cardiology Research Center, National Hopital Organization (OSAKA - NHO), Osaka National Hospital, Université de Brest (UBO), Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Graduate School, Endocrinology, ACS - Amsterdam Cardiovascular Sciences, Cardiology, Nursing, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, General Internal Medicine, Giugliano, Rp, Ruff, Ct, Braunwald, E, Murphy, Sa, Wiviott, Sd, Halperin, Jl, Waldo, Al, Ezekowitz, Md, Weitz, Ji, Špinar, J, Ruzyllo, W, Ruda, M, Koretsune, Y, Betcher, J, Shi, M, Grip, Lt, Patel, Sp, Patel, I, Hanyok, Jj, Mercuri, M, Antman, Em, Comi, Giancarlo, ENGAGE AF TIMI 48, Investigators, Robert P., Giugliano, Christian T., Ruff, Eugene, Braunwald, Sabina A., Murphy, Stephen D., Wiviott, Jonathan L., Halperin, Albert L., Waldo, Michael D., Ezekowitz, Jeffrey I., Weitz, Jind?ich, ?pinar, Witold, Ruzyllo, Mikhail, Ruda, Yukihiro, Koretsune, Joshua, Betcher, Minggao, Shi, Laura T., Grip, Shirali P., Patel, Indravadan, Patel, James J., Hanyok, Michele, Mercuri, Elliott M., Antman, Morin, Se, Hoffman, Eb, Deenadayalu, N, Grip, L, Lanz, H, Curt, V, Duggal, A, Hanyok, J, Davé, J, Morgan, D, Choi, Y, Jin, J, Xie, J, Crerand, W, Kappelhof, J, Maxwell, W, Skinner, M, Patel, S, Selicato, G, Otto C., Jr, Reissner, C, Smith, K, Ostroske, J, Ron, A, Giugliano, R, Connolly, S, Camm, J, Ezekowitz, M, Halperin, J, Waldo, A, Paolasso, E, Aylward, P, Heidbuchel, H, Nicolau, Jc, Goudev, A, Roy, D, Weitz, J, Corbalán, R, Yang, Y, Botero, R, Bergovec, M, Ŝpinar, J, Grande, P, Hassager, C, Voitk, J, Huikuri, H, Nieminen, M, Blanc, Jj, Leheuzey, Jy, Mitrovic, V, Alexopoulos, D, Sotomora, G, Kiss, R, Somaraju, B, Lewis, B, Merlini, P, Metra, M, Yamashita, T, García 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Grammer, M.
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Male ,Pyridines ,[SDV]Life Sciences [q-bio] ,Embolism ,Kaplan-Meier Estimate ,030204 cardiovascular system & hematology ,chemistry.chemical_compound ,0302 clinical medicine ,Edoxaban ,Atrial Fibrillation ,MESH: Double-Blind Method ,030212 general & internal medicine ,MESH: Warfarin ,Stroke ,MESH: Aged ,MESH: Middle Aged ,Cardiovascular diseases [NCEBP 14] ,Hazard ratio ,General Medicine ,MESH: Follow-Up Studies ,Middle Aged ,3. Good health ,MESH: Atrial Fibrillation ,Cardiovascular Diseases ,Anesthesia ,Cardiology ,Female ,Adult ,Aged ,Anticoagulants ,Double-Blind Method ,Follow-Up Studies ,Hemorrhage ,Humans ,Thiazoles ,Warfarin ,MESH: Hemorrhage ,Andexanet alfa ,medicine.drug ,medicine.medical_specialty ,MESH: Enoxaparin ,MESH: Anticoagulants ,MESH: Stroke ,Dabigatran ,03 medical and health sciences ,Internal medicine ,medicine ,MESH: Kaplan-Meier Estimate ,Rivaroxaban ,MESH: Humans ,business.industry ,MESH: Cardiovascular Diseases ,MESH: Adult ,medicine.disease ,Confidence interval ,MESH: Male ,chemistry ,business ,MESH: Female ,MESH: Embolism - Abstract
Contains fulltext : 125374.pdf (Publisher’s version ) (Open Access) BACKGROUND: Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects. The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known. METHODS: We conducted a randomized, double-blind, double-dummy trial comparing two once-daily regimens of edoxaban with warfarin in 21,105 patients with moderate-to-high-risk atrial fibrillation (median follow-up, 2.8 years). The primary efficacy end point was stroke or systemic embolism. Each edoxaban regimen was tested for noninferiority to warfarin during the treatment period. The principal safety end point was major bleeding. RESULTS: The annualized rate of the primary end point during treatment was 1.50% with warfarin (median time in the therapeutic range, 68.4%), as compared with 1.18% with high-dose edoxaban (hazard ratio, 0.79; 97.5% confidence interval [CI], 0.63 to 0.99; P
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- 2013
3. Impact of Spontaneous Extracranial Bleeding Events on Health State Utility in Patients with Atrial Fibrillation: Results from the ENGAGE AF‐TIMI 48 Trial
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Senior, R., Paul, J., McKnight, T., Formoso, I., Saravia Toledo, S., Codutti, O., Sanjurjo, M., Bowen, L., Sanchez, A., Alvarez, M., Rodriguez, M., Navarrete, S., Ramos, H., Venturini, C., Prado, A., Fernandez, E., Pozzer, D., Casares, E., Povedano, G., Tommasi, A., Piskorz, D., Verdini, E., Nul, D., Gandur, H., Muntaner, J., Funes, I., Marino, J., Calderon, M., Manuale, O., Carne, M., Mackinnon, I., Raimondi, G., Lotti, J., Shatsky, K., Rodkey, K., Lorente, C., Vignau, S., Llanos, J., Nigro, A., Litvak, B., Iglesias, M., Liniado, G., Belcuore, M., Lanternier, G., Monaco, F., Kevorkian, R., Jure, D., Jure, H., Bianchini, M., Avery, D., Hominal, M., von Wulffen, M., McKenzie, M., Miranda, J., Wright, L., Pye, M., Flint, L., Newby, D., Andrews, A., Goicoechea, R., Huerta, M., Giannaula, R., Eden, M., Giacomi, G., Ceirano, C., Garrido, M., Perlo, D., Garcia Duran, R., Meiller, F., Gant Lopez, J., Zanotti, A., Fuselli, J., Arrieta, M., Femenia, F., Falu, E., Facello, M., Facello, A., Murdoch, D., Helliwell, L., More, R., Isted, C., Maxwell, T., Jones, D., Marazzi, P., McGhee, C., MacLeod, M., Ebano, P., MacCallum, P., Davolos, M., Estol, C., Moreno, V., Dran, R., Cendali, G., D'Amico, A., Bocanera, M., Cuneo, C., Rosell, M., Cuello, J., Morandini, M., Colombo, H., Brown, R., Saa Zarandon, R., Caruso, O., Novas, V., Cartasegna, L., Fracaro, V., Caccavo, A., Saravia, M., Bustamante Labarta, G., Valle, M., Budassi, N., Lip, G., Finlayson, M., Linker, N., McGuire, K., Atkinson, C., Lindsay, S., Ramasamy, V., Lie, F., Dickinson, D., Douglas, H., D'Costa, D., Wilmott, R., Cohen, A., Duff, J., Choy, A., Davies, D., Chapman, O., Dougal, K., Camm, J., Price, R., Blagden, M., Schwarz, L., McGarvey, J., Stubbs, L., McCartney, M., Hicks, T., Massin, E., Bedenko, E., Marenberg, M., Rabadi-Marar, D., Dunn, S., Beeton, I., Smith, S., Aggarwal, R., Marar, I., Hernandez, S., Berli, M., Petrucci, J., Beloscar, J., Caceres, M., Amuchastegui, M., Ameriso, P., Ameriso, S., Garcia, M., Alvarez, C., Reguero, M., Allall, O., Rosales, E., Albisu, J., Ahuad Guerrero, R., Gonzalez, C., Vogelmann, O., Magnuson, Elizabeth A., Cohen, David J., Giugliano, Robert P., Mandviwala, M., Casas, R., Makam, S., Lisiecki, B., Mainigi, S., Doctor, A., Magee, A., Bush, D., Macomber, J., Edelstein, J., Lurie, M., Wright, H., Lui, H., Ault, S., Looby, R., Davids, M., Lone, B., Shah, D., Lomnitz, D., Wofford, E., Littlefield, R., Murphy, R., Ling, L., Miller, D., Lillestol, M., Bonds, C., Lewis, D., Hartley, L., Lesser, M., Smith, D., Lentz, M., Royse, H., Ledbetter, L., Faucett, S., Langevin, E., Simmons, T., Lang, J., Ferguson, D., Landau, C., Coyle, G. Stagi, Lambert, C., Jauregui, V., Laliotis, A., Marquez, D., Krichmar, P., Watts, S., Kozlowski, J., Sanchez, E., Kotha, P., Godfrey, C., Korpas, D., Averett, P., Kindman, L., Khan, G., Khan, M., Binns, M., Khan, B., DiCorcia, L., Kesselbrenner, M., Buhler, A., Kersh, R., Bartholomaus, D., Kerkering, M., Keller, J., Keller, R., Davis, C., Kastelic, R., Behm, K., Karunaratne, H., Ruggiero, M., Kapoor, A., Cook, S., Kaplan, K., Kostedt, G., Kandath, D., Dugal, J., Kai, W., Coombs, V., Kahn, B., Royes, A., Judson, P., Nichols, M., Jovin, I., Hughett, G., Jones, R., Phillips, T., Johnson, F., Andresen, T., Jardula, M., Butcher, S., Ison, R., Tambawala, M., Hussain, M., Garza, M., Hurst, P., Battistelli, E., Hunter, J., Truva, C., Huang, P., Craft, D., Howard, L., Hays, D., Howard, V., Adams, K., Houchin, V., Turner, N., Hotchkiss, D., Sloss, D., Horton, K., Homayouni, A., Homan, J., Young, C., Hoekstra, J., Dutter, S., Hippert, R., Vieira, P., Hinchman, D., Carey, G., Herson, S., Miranda, D., Herrod, J., Batchell, K., Hermany, P., Harkins, V., Henry, S., Millard, D., Henderson, D., Dandekar, U., Heiman, M., Krater, C., Hearne, S., Bobade, M., Harris, J., Cavanna, L., Han, M., Bentivenga, L., Hamroff, G., Morelli, L., Hack, T., McLean, R., Gvora, T., Felsman, D., Guthrie, R., Foster, B., Guerrero, Guerrero, Fisher, M., Guarnieri, T., Gabela, W., Guarino, J., Mabe, K., Grove, D., Davis, A., Grossman, C., Goodman, V., Griffin, J., Aull, L., Griffin, S., Bonora, M., Graham, S., Rafala, E., Gowda, S., Goldstein, M., Latteri, J., Goldscher, D., Ewing, B., Gogia, H., Keane-Richmond, P., Gillespie, E., Hinchion, N., Gerber, J., Valentine, H., George, F., Garb, J., Jones, J., Gaffney, M., Smith, K., Friedlander, I., Morales, C., French, W., Gentry, P., Franco, M., Thrope, C., Frais, M., Solis, A., Forman, S., Slayton, C., Flores, E., Donahue, S., Fishbein, G., Drew, B., Fischell, T., Lim, G., Finkelstein, S., Shriver, D., Finkel, M., Calvo, M., Fialkow, J., Prior, J., Felten, W., Tang, N., Feldman, J., Tameron, A., Feld, L., Watkins, D., Fahmy, R., DeSalle, D., Everhart, B., Shipp, A., Ettinger, N., O'Brien, J., Johnson, C., Erenrich, N., Cristaldi, J., Ellis, J., Quick, R., Eldadah, Z., Dunn, K., Eade, J., Cullen, T., D'Souza, A., Habibi, S., Drozdiak, R., Olson, A., Dotani, I., Rodriguez, L., Donovan, D., Tisdale, L., DiGiovanna, M., Ucik, S., Dhar, S., Briscoe, C., Devenport, S., Waters, L., Desire, A., Steward, A., Desai, A., Carey, J., DeGarmo, R., Warmack, D., Dean, J., Debes, C., De Lemos, J., Ebreo, N., Davuluri, A., Dave, B., Dave, K., Wulf, A., Datta, S., Leka, G., Daniels, S., Morgan, T., Dang, N., Sarpola, N., Curtis, B., Nelson, L., Cowan, L., Masson, E., Cottiero, R., Mullinax, K., Cossu, S., Svadbik, L., Corbett, B., Martinez, E., Concha, M., Cole, J., Salpas, S., Colan, D., Bossaers, J., Cohen, R., Dutka, C., McClelland, M., Clay, A., Clapp, T., Bagby, J., Ciaramita, J., Sawaya, K., Chaturvedi, S., Tamayo, M., Charlat, M., Hatfield, G., Chang, M., Phan, D., Carr, K., Jameson, L., Caplan, J., Hartranft, E., Canosa, R., Canaday, D., Morton, S., Cader, C., Al-Maliky, T., Bybee, K., Triano, A., Brown, H., Frey, W., Brilakis, E., Terry, P., Bradley, A., Ziegler, K., Bowden, W., Wade, W., Bouchard, A., Hickenbotham, D., Borsheim, M., Vernon, M., Blue, B., Bloomberg, K., Bloomberg, R., Ensminger, E., Blonder, R., Talbot-Lawson, C., Block, T., Antonino, M., Bingham, S., Langone, L., Bilazarian, S., Preston, S., Bilal, B., Eldred, R., Bernard, J., Ibarra, M., Berk, M., Garman, V., Bensimhon, D., Swaim, D., Beinart, S., Craig, M., Bedwell, N., Luis-Valdes, M., Bedoya, R., Hoffman, T., Beasley, R., Benton, J., Bartkowiak, A., Gordon, L., Barrington, P., Faircloth, C., Barker, T., Altonen, D., Barber, M., Campbell, G., Baman, R., Batista, M., Baine, S., Thompson, B., Ayesu, K., Baldwin, E., Awasty, V., Cobos, D., Aude, Y., Strickland, S., Attanti, S., Rasmussen, L., Arouni, A., Shoaf, R., Arnold, T., York, T., Anderson, J., Persechino, F., Amin, M., Khetarpal, S., Amin, K., Lane, B., Alsheikh, T., MacDonald, H., Almquist, A., Biscardi, R., Allison, J., Godsey, W., Aliyar, P., Genova-Peeva, E., Alexander, J., Brubaker, S., Akhter, F., Ahmadpour, H., Hussain, A., Ahmad, A., Beck, P., Reiling, S., Adler, P., Barash, B., Adler, J., Lohman, J., Panella, M., Abi-Mansour, P., Roberts, J., Mackin, A., Moriarty, A., Green, M., Shandra, T., Zhurba, S., Logvinov, Y., Zharinov, O., Mudruk, I., Yena, L., Nahrebetskyy, V., Yagensky, A., Serik, S., Volkov, V., Goncharov, O., Vizir, V., Sklyanna, O., Vatutin, M., Drapchak, I., Vakaliuk, I., Tykhonova, S., Kuznetsov, I., Tseluyko, V., Lyzohub, S., Sychov, O., Perebetiuk, L., Stanislavchuk, M., Sirenko, Y., Zamlynskyy, M., Shvetz, N., Goncharova, I., Shcherbak, V., Ishchuk, V., Shatilo, V., Rudyk, I., Chendey, T., Rishko, M., Gamachek, O., Rebrov, B., Leonidova, V., Prokhorov, O., Nekrasa, A., Potapenko, P., Dovgan, N., Parkhomenko, A., Ushakova-Sokolova, L., Ostrovska, L., Fedotov, S., Malynovsky, Y., Gorna, O., Lizogub, V., Kyyak, Y., Kupnovytska, I., Stets, R., Kraydashenko, O., Usan, N., Kraiz, I., Kaplan, P., Koval', O., Ohirko, O., Koval, V., Dvoieglazova, M., Kotseruba, V., Petyunina, O., Kopytsya, M., Vasylets, V., Kolomyyits, S., Gerasimenko, N., Kaydashev, I., Blihar, O., Karpenko, Y., Nevolina, I., Karpenko, O., Samburg, Y., Godlevska, O., Husyev, V., Horbach, L., Dzublik, Y., Gavrysyuk, V., Sorokivskyy, M., Faynyk, A., Vasilyeva, L., Dzyak, G., Kulynych, R., Dotsenko, S., Lebedynskaya, M., Bereznyakov, I., Vlasyuk, Z., Bazylevych, A., Azhdari, M., Batushkin, V., Zoghi, M., Yigit, Z., Yigit, F., Tandogan, I., Turgut, O., Oto, A., Kanadasi, M., Kabul, K., Ermis, C., Erdogan, D., Ceyhan, C., Cayli, M., Calik, A., Cakmak, N., Bayata, S., Ata, N., Demir, H., Akilli, H., Acikel, M., Puripun, E., Vorasettakarnkij, Y., Mekara, W., Sukonthasarn, A., Panpunuan, P., Sritara, P., Sripracha, A., Piyayotai, D., Bamrungpong, P., Laothavorn, P., Sriprasert, S., Kiatchoosakun, S., Sinthusopa, W., Kaewsuwanna, P., Pornchaiyasit, K., Jirasirirojanakorn, K., Kuo, J. Y., Yeh, H. I., Tsai, W. C., Lee, S. C., Ueng, K. C., Pan, Y. F., Tseng, W. K., Chiu, C. Z., Shyu, K. G., Lin, K. H., Pai, P. Y., Lee, J. T., Lin, T. H., Lai, W. T., Wang, C. L., Kuo, C. T., Chen, Y. F., Huang, J. L., Chen, Y. P., Hsia, C. H., Yeh, T. C., Chiou, C. W., Wu, Y. W., Chiang, F. T., Yu, W. C., Chiang, C. E., Wu, W. S., Cheng, C. C., Slater, I. Petrova, Moccetti, T., Broberg, M., Thulin, J., Gunnarsson, A., Stenberg, A., Sundholm, C., Ronn, F., Johansson, M., Rautio, A., Moodh, J., Randers, F., Eriksson, G., Malmqvist, L., Edlund, M., Kozak, P., Hakansson, E., Koskinen, P., Jernhed, H., Juul-Moller, S., Winberg, L., Herlitz, J., Karlsson, L., Engdahl, J., Ostberg, S., Dettmann, S., Bengtsson, A. Stener, Carlsson, T., Persson, L., Blomstrom, P., Andersson, R., Blom, K. Berndtsson, Akerberg, A., Appelros, P., Astier, L., Villuendas, R., Dachs Delgado, M., Terns, M., Fernandez Alvarez, R., Fernandez, M., Arias, J., Diaz-Pintado, M., Merino, J., Blanco Abril, S., Manzano, L., Barquero, R., Lopez Garcia-Aranda, V., Delgado, A., Hernandez Madrid, A., Moure, M., Gonzalez Juanatey, J., Perez Guevara, M., Diez Tejedor, E., Asensio, A., De Arce Borda, A., Calvo, G., Calvo, C., Cabero, P., Bruguera Cortada, J., Puertas, I., Blanco Coronado, J., Manzanal Rey, A., Arcocha Torres, M., Kim, J. Y., Rim, S. J., Na, J. O., Rha, S. W., Kwak, J. J., Namgung, J., Shin, D. G., Lee, S. H., Joung, B. Y., Lee, M. H., Chun, M. Y., Kim, Y. J., Seo, J. B., Kim, S. H., Park, S. J., Kim, J. S., Park, J. H., Kim, J. H., Park, M. S., Kim, J. T., Cha, M. J., Kim, H. S., Seo, J. S., Kim, D. S., Jin, E. S., Kim, C. J., Choi, K. J., Kang, D. H., Lee, J. M., Jeon, H. K., Jung, J. W., Hyon, M. S., Lee, H. W., Hong, T. J., Lee, K. H., Han, S. H., Oh, Y. S., Chung, W. S., Hong, K. S., Choi, H. H., Ryu, D. R., Cho, B. R., Kim, D. H., Cha, J. K., Han, M. G., Bae, H. J., Wessels, L., Venter, T., Le Roux, M., Van Zyl, L., Goosen, Y., Van Der Merwe, N., Johnston, H., Soma, P., Munnik, M., Snyders, F., Duki, Y., Naidoo, D., Taljaard, J., Mitha, I., Kelfkens, Y., Wilson, L., Gani, M., Nunkoo, T., Essop, M., Mostert, M., Engelbrecht, J., Botha, L., Ellis, G., Allman, J., Dalby, A., Poynton, M., Basson, M., Erasmus, L., Badenhorst, J., Bollova, D., Zareczky, P., Kokles, M., Zachar, A., Kmec, J., Slanina, M., Morsky, J., Ruffini, L., Fedacko, J., Pella, D., Mazur, J., Reptova, A., Kasperova, V., Hofmanova, J., Hranai, M., Hatala, R., Hatalova, K., Dzupinova, M., Dzupina, A., Vankova, L., Duris, T., Dulka, T., Dulkova, K., Kosmalova, V., Dukat, A., Banikova, A., Ambrovic, I., Ambrovicova, V., Tesic, M., Golshmid, M., Ruda, M., Topolnitchi, O., Castro, C., Ostojic, M., Tesic, B. Vujisic, Mitrovic, P., Vasiljevic-Pokrajcic, Z., Davicevic, Z., Tavciovski, D., Milinkovic, I., Seferovic, P., Kalezic, T., Putnikovic, B., Polovina, M., Potpara, T., Tasic, N., Otasevic, P., Djokic, I., Miloradovic, V., Djokovic, A., Krotin, M., Ilic, B., Ilic, S., Erceg, P., Despotovic, N., Bjelobrk, M., Adjic, N. Cemerlic, Majstorovic, A., Celic, V., Djordjevic-Radojkovic, D., Apostolovic, S., Motylev, I., Zubeeva, G., Kononenko, O., Zenin, S., Mankhaeva, B., Zateyshchikova, A., Zotova, I., Zateyshchikov, D., Nikulina, N., Yakushin, S., Petrochenko, A., Yakusevich, V., Rodina, N., Volkov, D., Kirgizova, A., Vishnevsky, A., Rossovskaya, M., Ustyugov, S., Bulygin, S., Timofeev, A., Solovyev, A., Tikhonova, E., Kositsyna, I., Tereshenko, S., Isakov, L., Tarasov, N., Dronov, D., Suprun, E., Erofeeva, S., Sobolev, K., Lapidus, N., Sizova, Z., Orlov, V., Sinitsina, I., Vorontsova, S., Sidorenko, B., Agirov, M., Shogenov, Z., Lebedev, E., Shaposhnik, I., Repin, M., Karoli, N., Rebrov, A., Letaeva, M., Raskina, T., Pikalova, N., Poluyanova, N., Matveeva, I., Polkanova, E., Nilk, R., Panov, A., Laguta, P., Panchenko, E., Patrusheva, S., Novikova, N., Khromova, O., Nikolskaya, I., Nikolaev, A., Nikolaev, K., Lamden, D., Lukyanov, Y., Belousova, L., Lila, A., Moiseeva, Y., Libov, I., Maslova, A., Libis, R., Volkova, E., Levashov, S., Tereschenko, L., Lavrova, O., Rychkov, A., Kuznetsov, V., Kostenko, O., Kozyrev, O., Polyanskaya, E., Koziolova, N., Karabalieva, S., Kostenko, V., Khrustalev, A., Khrustalev, O., Tsareva, E., Khokhlov, R., Sinitsina, O., Khokhlov, A., Kireenkov, I., Khirmanov, V., Kosenko, B., Buza, V., Karpov, Y., Mazovets, O., Gratsiansky, N., Laptev, I., Goloshchekin, B., Kratskina, T., Golitsyn, S., Valovyeva, S., Glezer, M., Valuyshkih, E., Gilinskaya, O., Soin, I., Filatov, A., Kirichek, N., Esip, V., Egorova, L., Zyatenkova, E., Drapkina, O., Puchinyan, N., Dovgalevsky, P., Masin, A., Demko, A., Pokutneva, O., Chumakova, G., Khlevchuk, T., Bokarev, I., Yukhno, E., Berns, S., Kosolapov, Y., Belenky, D., Larina, V., Bart, B., Bashkireva, A., Barbarash, O., Alexandrova, L., Ballyuzek, M., Chernyavskaya, T., Arutyunov, G., Zhukova, N., Tudoran, C., Tudoran, M., Topolnitchi, L., Spinu, C., Stamate, S., Plosca, P., Sipciu, D., Ardelean, A., Popescu, M., Cozma, M., Pop, C., Serban, D., Minescu, B., Costache, L., Iosipescu, L., Jurca, S., Dragomir, D., Sirbu, I., Dobreanu, D., Voicu, O., Dobre, I., Jemna, D., Crisu, D., Anciu, M., Cristea, M., Parasteac, M., Creteanu, M., Constantinescu, M., Ghionea, M., Coman, I., Andor, M., Ciobotaru, G., Bolohan, F., Doka, B., Bobescu, E., Ochean, V., Bengus, C., Badila, E., Bartos, D., Matei, C., Apetrei, E., Ciortea, M., Albulescu, P., Soares, D., Santos, J., Veiga Pais Nunes, L., Santos, O., Goncalves, A., Salgado, A., Leitao Marques, A., Oliveira, D., Monteiro, P., Neves, E., Martins, D., Maymone, D., Madeira, J., Lopes, S., Gil, V., Correia, J., Matias, F., Nawrot, M., Zielinski, M., Krauze, R., Zarebinski, M., Kudlicki, J., Wysokinski, A., Muzalewski, P., Wrobel, W., Turbak, R., Malanska, A., Szolkiewicz, M., Spyra, J., Sendrowski, D., Norwa-Otto, B., Ruzyllo, W., Ronkowski, R., Rozmyslowicz-Szerminska, W., Rewinska, H., Zienciuk-Krajka, A., Raczak, G., Bojanowska, E., Polaszewska-Pulkownik, V., Pogorzelska, H., Janczewska, D., Podjacka, D., Olszewski, M., Nowak, J., Nej, A., Niezgoda, K., Nessler, B., Nessler, J., Biniek, D., Napora, P., Myslinski, W., Mosiewicz, J., Kosmalska, K., Miekus, P., Chmielowski, A., Mazur, S., Kosmaczewska, A., Wnetrzak-Michalska, R., Sznajder, R., Matyszczak-Toniak, L., Jaguszewska, G., Lysek, R., Szymanska, K., Lubinski, A., Stopyra-Poczatek, M., Lewczuk, J., Wierzykowski, T., Lesnik, J., Kus, W., Sklodowskiej-Curie, M., Muzyk-Osikowicz, M., Krzyzanowski, W., Borowski, W., Korzeniak, R., Benicka, E., Konieczny, M., Kaliszczak, R., Karczmarczyk, A., Tymendorf, K., Kania, G., Kaminski, L., Pacholska, A., Kaczmarek, B., Jurowiecki, J., Ciezak, P., Jazwinska-Tarnawska, E., Makowiecka-Ciesla, M., Januszewicz, A., Mroczkowski, P., Gniot, J., Zajac, E., Gieroba, A., Guziewicz, M., Domanska, E., Laskowska-Derlaga, E., Derlaga, B., Ptak, A., Dabrowska, M., Cymerman, K., Krzystolik, A., Busz-Papiez, B., Cieslak, B., Bronisz, M., Baszak, J., Korzeniowska-Adamus, J., Adamus, J., Nario, K., Villamor, L., Aquino, M., To, R., Gilo, L., Roxas, A., Joaquin, F., Rogelio, G., Enad, C., Matiga, G., Vallenas, M., Coching, R., Zapanta, M., Barcinas, R., Sambaz, C. 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L., Zhou, S. X., Li, B. G., Zheng, Z. Q., Wang, J. Q., Zhao, X. L., Han, R. J., Zhao, R. P., Kang, H., Zhang, Z., Lin, Y. N., Zhang, H. Q., Qiang, H., Yuan, Z. Y., Li, L. L., Yu, B., Xu, Y. P., Yin, Y. H., Gao, M., Zheng, Y., Zheng, X., Yang, Y. J., Li, A. Y., Yang, K., Liang, Y. Z., Xu, Y. M., Gu, J. Y., Xu, J. H., Li, Y. E., Wu, S. L., Huang, D., Wei, M., Shi, X. J., Wang, G. P., Qi, S. Y., Wang, D. M., Yang, Z. Y., Ma, S. M., Lu, Z. H., Liu, L., Gu, X. J., Liao, D. N., Liu, Y., Li, Z. Q., Liu, B., Li, W. M., Kong, Y. Q., Li, T. F., Liu, H., Li, L., Qu, Z., Jiang, X. J., Qiu, Y., Hong, L., You, Z. G., Hong, K., Zhang, P., Fu, G. S., Feng, C., Dong, Y. G., Zhang, X., Chen, X. P., Xie, X. D., Chen, J. Z., Xu, G. 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Burger, Zimmermann, S., Almeida, M., Boas, F. Villas, Lustosa, E., Sobral Filho, D., Carraro, A., Simoes, M., Vicente, C., Saraiva, J., do Val, R., Sampaio, R., Pagnan, L. Goncalves, dos Santos, F. Rossi, Rodrigues, D., Rodrigues, A., Rocha, M. Rubia, Rodrigues, L., Barros, R., Rocha, J., Leipelt, J., Katz Weiand, L. Reis, Avellar, K., Reis, G., Gozalo, A., Almeida, J. Pimenta, Luiz, R. Osorio, Leaes, P., Morales, K., Sebba Barroso de Souza, W. Kunz, Radaelli, G., Kalil, C., Almeida, A., Kaiser, S., Cury, C., Jorge, J., Pereira, L., Jaeger, C., Ninho, L., Guimaraes, A., Gomes, A., Gomes, M., Pereira, G., Gagliardi, R., Daitz, C., Finimundi, H., Araujo, E., Ferreira, L., Seroqui, M., Saporito, W. Faustino, Morgado, S., Dutra, O., Laimer, R., Duda, N., Pereira, V., De Patta, M., Barroso, D., Costantini, C., Silva, J., Chaves Junior, H., Fleck, N., Brondani, R., Cunha, S., Botelho, R., Sehnem, E., Precoma, D. Bertolim, Ferraz, R. Franchin, Alves da Costa, F. Augusto, Motta, C., Atie, J., de Melo, R. Ferreira, Lotufo, P. Andrade, Coutinho, E., Vincenzo de Paola, A. Amato, Denie, D., Wollaert, B., Beerts, C., Vrolix, M., Mestdagh, I., Vervoort, G., van Welden, J., Vanwelden, J., Derycker, K., Vandekerckhove, Y., Jacobs, C., Mehrle, A., Skinner, J., Meholick, A., Marti, J., Mega, J., Lack, A., Stockman, D., Huyberechts, D., Scavee, C., Clinckemaille, N., Parque, J., Raepers, M., Mairesse, G., Malmendier, D., Herzet, J., Meeusen, K., Heidbuchel, H., Tincani, G., Desfontaines, P., De Bruyne, L., De Tollenaere, M., de Koning, K., De Bleecker, J., Banaeian, F., Capiau, L., O'Shea, V., Szto, G., Perrett, L., Purnell, P., Batta, C., Paul, V., Li, J., McKeirnan, M., Morrison, H., Wright, J., Wright, A., Chung, A., Watkin, R., Gilchrist, M., Venkataraman, A., Lehman, R., Jones, S., Gates, P., Flecknoe-Brown, S., Silver, G., Davis, S., Kay, S., Dart, A., Slattery, A., Crimmins, D., Price-Smith, S., Colquhoun, D., Hoffmann, B., Arstall, M., Paraskevaidis, T., Anderson, C., Morell, Y., Vico, M., Teves, M., Sosa Liprandi, M., Morara, P., Severino, P., Buzzetti, C., Schygiel, P., Walker, M., Turner, W., Bridge, C., Storey, R., Goloboulicz, A., Schmidberg, J., Kennard, S., Sopher, M., McLaurin, B., Young, G., Kwong, Winghan J., Antman, Elliott M., Ruff, Christian T., Wang, J. H., Iriarte, M., Morissette, A., Wang, Kaijun, Li, Haiyan, and Yalcin, R.
- Subjects
Male ,medicine.medical_specialty ,Complications ,Time Factors ,Pyridines ,Health Status ,Embolism ,Hemorrhage ,Arrhythmias ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,Quality of life ,Risk Factors ,Surveys and Questionnaires ,Internal medicine ,Atrial Fibrillation ,Humans ,Medicine ,In patient ,Prospective Studies ,030212 general & internal medicine ,anticoagulation ,Blood Coagulation ,Original Research ,Aged ,Aged, 80 and over ,Quality and Outcomes ,business.industry ,Anticoagulants ,Atrial fibrillation ,Middle Aged ,bleeding ,medicine.disease ,Stroke ,Thiazoles ,Treatment Outcome ,quality of life ,utility ,Physical therapy ,Cardiology ,Female ,Warfarin ,Gastrointestinal Hemorrhage ,Cardiology and Cardiovascular Medicine ,business ,TIMI ,Health Services and Outcomes Research ,Factor Xa Inhibitors - Abstract
Background The impact of different types of extracranial bleeding events on health‐related quality of life and health‐state utility among patients with atrial fibrillation is not well understood. Methods and Results The ENGAGE AF ‐ TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial Infarction 48) Trial compared edoxaban with warfarin with respect to the prevention of stroke or systemic embolism in atrial fibrillation. Data from the EuroQol‐5D ( EQ ‐5D‐3L) questionnaire, prospectively collected at 3‐month intervals for up to 48 months, were used to estimate the impact of different categories of bleeding events on health‐state utility over 12 months following the event. Longitudinal mixed‐effect models revealed that major gastrointestinal bleeds and major nongastrointestinal bleeds were associated with significant immediate decreases in utility scores (−0.029 [−0.044 to −0.014; P P =0.001], respectively). These effects decreased in magnitude over time, and were no longer significant for major nongastrointestinal bleeds at 9 months, but remained borderline significant for major gastrointestinal bleeds at 12 months. Clinically relevant nonmajor and minor bleeds were associated with smaller but measurable immediate impacts on utility (−0.010 [−0.016 to −0.005] and −0.016 [−0.024 to −0.008]; P Conclusions All categories of bleeding events were associated with negative impacts on health‐state utility in patients with atrial fibrillation. Major bleeds were associated with relatively large immediate decreases in utility scores that gradually diminished over 12 months; clinically relevant nonmajor and minor bleeds were associated with smaller immediate decreases in utility that persisted over 12 months. Clinical Trial Registration URL: https://www.clinicaltrials.gov/ . Unique identifier: NCT00781391.
- Published
- 2017
4. Outcomes With Edoxaban Versus Warfarin in Patients With Previous Cerebrovascular Events Findings From ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48)
- Author
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Pan, Y. F., Lim, G., Desire, A., Tseng, W. K., Rost, Natalia S., Grammer, M., Khetarpal, S., Waseem, M., Zellner, C., Roper, E., Amin, M., Harden, M., Sababathi, R., Valpas, S., Bourlios, P., Kawaguchi, A., Mavronasiou, E., Pandurangi, U., Shams, S., Dichristin, U., Purayil, M. Padinhare, Munemasa, M., Angel, J., Gurusamy, P., Berni, A., Platner, N., Zeltser, D., El Jarroudi, M., Kisos, D., Haruna, T., Bernhardt, P., Coisne, D., Nakahara, Y., Li, W. M., Karamitsos, C., Tziortziotis, A., Essop, M., Nunkoo, T., Gani, M., Wilson, L., Kelfkens, Y., Mitha, I., Taljaard, J., Naidoo, D., Duki, Y., Snyders, F., Munnik, M., Soma, P., Johnston, H., Patki, N., Jasani, B., Van Der Merwe, N., Goosen, Y., Van Zyl, L., Le Roux, M., Venter, T., Wessels, L., Bae, H. J., Han, M. G., Cha, J. K., Kim, D. H., Cho, B. R., Ryu, D. R., Choi, H. H., Hong, K. S., Chung, W. S., Oh, Y. S., Han, S. H., Lee, K. H., Hong, T. J., Lee, H. W., Hyon, M. S., Jung, J. W., Jeon, H. K., Lee, J. M., Kang, D. H., Choi, K. 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Avraham, Elias, M., Kaneno, Y., Badenhorst, J., Carey, G., Herson, S., Ebina, E., Meno, H., Arora, V., Endo, H., Memon, A., Fattore, L., Miranda, D., Herrod, J., Batchell, K., Hermany, P., Harkins, V., Henry, S., Millard, D., Henderson, D., Jirasirirojanakorn, K., Pornchaiyasit, K., Kaewsuwanna, P., Sinthusopa, W., Kiatchoosakun, S., Dandekar, U., Heiman, M., Krater, C., Sriprasert, S., Laothavorn, P., Hearne, S., Bobade, M., Bamrungpong, P., Harris, J., Cavanna, L., Han, M., Bentivenga, L., Hamroff, G., Morelli, L., Piyayotai, D., Hack, T., McLean, R., Gvora, T., Sripracha, A., Felsman, D., Guthrie, R., Foster, B., Guerrero, Guerrero, Sritara, P., Arneja, J., Ranka, R., Guarnieri, T., Gabela, W., Guarino, J., Mabe, K., Grove, D., Davis, A., Grossman, C., Goodman, V., Griffin, J., Aull, L., Panpunuan, P., Griffin, S., Bonora, M., Graham, S., Rafala, E., Gowda, S., Goldstein, M., Latteri, J., Goldscher, D., Ewing, B., Gogia, H., Keane-Richmond, P., Gillespie, E., Hinchion, N., Gerber, J., Valentine, H., George, F., Garb, J., Jones, J., Gaffney, M., Ramos, H., Sukonthasarn, A., Mekara, W., Vorasettakarnkij, Y., Agarwal, D., Abdullakutty, J., Puripun, E., Malhan, S., Kincses, M., Vertes, A., Acikel, M., Marosi, A., Tomcsanyi, J., Satake, M., Mita, T., Di Niro, M., Szakal, I., Di Pasquale, G., Akilli, H., Demir, H., Smith, K., Friedlander, I., Morales, C., French, W., Gentry, P., Franco, M., Thrope, C., Frais, M., Solis, A., Forman, S., Slayton, C., Flores, E., Donahue, S., Fishbein, G., Drew, B., Fischell, T., Finkelstein, S., Shriver, D., Ata, N., Bayata, S., Cakmak, N., Finkel, M., Calik, A., Erasmus, L., Basson, M., Calvo, M., Fialkow, J., Prior, J., Felten, W., Mazzone, C., Tang, N., Feldman, J., Tameron, A., Feld, L., Watkins, D., Cayli, M., Fahmy, R., DeSalle, D., Ceyhan, C., Everhart, B., Shipp, A., Ettinger, N., O'Brien, J., Johnson, C., Erenrich, N., Cristaldi, J., Ellis, J., Quick, R., Eldadah, Z., Dunn, K., Eade, J., Cullen, T., D'Souza, A., Habibi, S., Drozdiak, R., Olson, A., Dotani, I., Rodriguez, L., Donovan, D., Tisdale, L., DiGiovanna, M., Ucik, S., Dhar, S., Briscoe, C., Devenport, S., Waters, L., Steward, A., Desai, A., Poynton, M., Carey, J., DeGarmo, R., Warmack, D., Dean, J., Debes, C., De Lemos, J., Ebreo, N., Davuluri, A., Dave, B., Dave, K., Wulf, A., Datta, S., Leka, G., Daniels, S., Morgan, T., Dang, N., Sarpola, N., Curtis, B., Nelson, L., Cowan, L., Masson, E., Cottiero, R., Mullinax, K., Cossu, S., Svadbik, L., Corbett, B., Martinez, E., Concha, M., Cole, J., Salpas, S., Colan, D., Bossaers, J., Cohen, R., Dutka, C., Sipos, T., McClelland, M., Clay, A., Clapp, T., Bagby, J., Ciaramita, J., Sawaya, K., Chaturvedi, S., Tamayo, M., Charlat, M., Hatfield, G., Chang, M., Phan, D., Carr, K., Jameson, L., Caplan, J., Hartranft, E., Canosa, R., Canaday, D., Morton, S., Cader, C., Al-Maliky, T., Bybee, K., Navarrete, S., Ruzsa, D., Triano, A., Brown, H., Frey, W., Brilakis, E., Terry, P., Bradley, A., Ziegler, K., Bowden, W., Simor, T., Wade, W., Bognar, A., Bouchard, A., Hickenbotham, D., Borsheim, M., Vernon, M., Blue, B., Bloomberg, K., Bloomberg, R., Ensminger, E., Blonder, R., Talbot-Lawson, C., Block, T., Antonino, M., Bingham, S., Langone, L., Bilazarian, S., Bilal, B., Eldred, R., Bernard, J., Ibarra, M., Sayour, A., Toth, S. Rostasne, Palinkas, A., Berk, M., Nagy, A., Garman, V., Bensimhon, D., Swaim, D., Beinart, S., Craig, M., Bedwell, N., Luis-Valdes, M., Bedoya, R., Hoffman, T., Beasley, R., Kolumban, E., Merkely, B., Kiss, K., Wulf, M., Takeda, M., Benton, J., Bartkowiak, A., Gordon, L., Erdogan, D., Barrington, P., Faircloth, C., Barker, T., Altonen, D., Barber, M., Campbell, G., Baman, R., Batista, M., Baine, S., Thompson, B., Ayesu, K., Ermis, C., Alvarez, M., Sanchez, A., Bowen, L., Sanjurjo, M., Codutti, O., Saravia Toledo, S., Formoso, I., Schmidberg, J., Baldwin, E., Awasty, V., Cobos, D., Aude, Y., Strickland, S., Medvegy, M., Kiss, T., Attanti, S., Matoltsy, A., Rasmussen, L., Arouni, A., Shoaf, R., Arnold, T., York, T., Kabul, K., Kanadasi, M., Goloboulicz, A., Anderson, J., Schygiel, P., Buzzetti, C., Severino, P., Morara, P., Sosa Liprandi, M., Teves, M., Vico, M., Oto, A., Turgut, O., Persechino, F., Morell, Y., Amin, K., Lane, B., Alsheikh, T., MacDonald, H., Almquist, A., Anderson, C., Paraskevaidis, T., Kolk, R., Tandogan, I., Stern, A., Yigit, F., Yigit, Z., Arstall, M., Hoffmann, B., Colquhoun, D., Price-Smith, S., Crimmins, D., Slattery, A., Karakai, H. Horvathne, Lupkovics, G., Di Lenarda, A., Kovacs, Z., Gadepalli, R., Mariani, M., Kumagai, S., Luttermann, M., Krishnan, H., Dart, A., Venneklaas, U., Kay, S., Lueders, S., De Servi, S., Grosse, B., Davis, S., Baranyai, M., Silver, G., Flecknoe-Brown, S., Gates, P., Kovacs, I., Salminen, O., Koczka, M., Jakal, A., Jones, S., Pirelli, S., Lohrbaecher-Kozak, I., Bauch, F., Koenig, H., Lehman, R., Kiss, R., Saha, D., Barai, A., Roy, D., Bekal, S., Feil, J. Felfoldine, Meusel, P., Morrison, H., Biscardi, R., Kis, E., Hirayama, A., Allison, J., Godsey, W., Aliyar, P., Genova-Peeva, E., Kosztyu, M., Kleinecke-Pohl, U., Alexander, J., Brubaker, S., Akhter, F., Schoen, B., Reddy, R., Shankar, A. Ravi, Jungmair, W., Schmid, S., Junggeburth, J., De Pace, D., Ahmadpour, H., De Caterina, R., Hussain, A., Kaik, J., Ahmad, A., Beck, P., Zoghi, M., Batushkin, V., Fink, P., Reiling, S., Miyamoto, N., Adler, P., McKeirnan, M., Li, J., Paul, V., Batta, C., Serup-Hansen, K., Vuriya, A., Horacek, T., Schuppe, M., Kanakaridisz, N., Varga, A., Kimizu, T., Purnell, P., Perrett, L., Kishore, R., Szto, G., O'Shea, V., Capiau, L., Banaeian, F., De Bleecker, J., de Koning, K., De Tollenaere, M., Kara, M., Fiok, J., Szatmari, J., De Bruyne, L., Edes, I., Tsukimine, A., Muskoczki, E., Wiggers, H., Jakobsen, U., Torp-Pedersen, C., Forgione, C., Harada, K., Dioszeghy, P., Almaraz, S. Padilla, Desfontaines, P., Tincani, G., Heidbuchel, H., Camas, L. Velasquez, Cuccia, C., Meeusen, K., Herzet, J., Malmendier, D., Guerra, L., Mairesse, G., Raepers, M., Parque, J., Clinckemaille, N., Scavee, C., Samayoa, C. Sanchez, Pozuelos, J. Mayen, Arakawa, S., Huyberechts, D., Stockman, D., Jacobs, C., Vandekerckhove, Y., Svenningsen, A., Sand, N., Azhdari, M., Derycker, K., Peruzzotti, L., Comi, G., Vanwelden, J., Mino, K., Cervi, E., Sanchez, M., Gilat, T., van Welden, J., Vervoort, G., Mestdagh, I., Vrolix, M., Bazylevych, A., Vlasyuk, Z., Raae, D., Raymond, I., Beerts, C., Wollaert, B., Denie, D., Vincenzo de Paola, A. Amato, Coutinho, E., Lotufo, P. Andrade, de Melo, R. Ferreira, Atie, J., Motta, C., Alves da Costa, F. Augusto, Lahav, M., Estrada, M. Rodas, Ferraz, R. Franchin, Precoma, D. Bertolim, Guevara, S., Contzen, C., Weihrauch, D., Sehnem, E., Botelho, R., Cunha, S., Brondani, R., Fleck, N., Buhr, M., Kandekar, S., Ladenburger, K., Lavagnino, A. Ovando, Braun, R., Ishimaru, S., Chaves Junior, H., Silva, J., Costantini, C., Barroso, D., Jimenez, T., De Patta, M., Pereira, V., Duda, N., Bereznyakov, I., Laimer, R., Tomita, H., Ishii, Y., Dutra, O., Morgado, S., Saporito, W. Faustino, Seroqui, M., Ferreira, L., Araujo, E., Finimundi, H., Daitz, C., Gagliardi, R., Pereira, G., Gomes, M., Gomes, A., Guimaraes, A., Lebedynskaya, M., Petrovic, V., Overgaard, K., Ninho, L., Olsen, R., Nielsen, H., Jaeger, C., Barash, B., Veng-Olsen, T., Dotsenko, S., Pereira, L., Iversen, H., Madsen, H., Kulynych, R., Dzyak, G., Vasilyeva, L., Faynyk, A., Sorokivskyy, M., Gavrysyuk, V., Schnelzer, P., Ibsen, H., Adler, J., Dzublik, Y., Horbach, L., Husyev, V., Bouzo, M., Babbar, A., Loof, A., Blanc, J., Godlevska, O., Melgar, I. Guzman, Marcoviciu, D., Ramirez, V. de Leon, Sehr, B., Beyer-Westendorf, J., Vierbeck, S., Decoulx, E., Samburg, Y., Jorge, J., Cury, C., Karpenko, O., Hassager, C., Milla, O. Ayau, Kaiser, S., Christensen, L., Christensen, H., Dodt, K., Zidkova, E., Samkova, D., Vodnansky, P., Almeida, A., Kalil, C., Radaelli, G., Sebba Barroso de Souza, W. Kunz, Morales, K., Labrova, R., Nevolina, I., Karpenko, Y., Leaes, P., Luiz, R. Osorio, Blihar, O., Kaydashev, I., Berbari, H., Spinar, J., Spacek, R., Almeida, J. Pimenta, Gozalo, A., Slaby, J., Reichert, P., Jirsova, E., Podrazil, P., Gerasimenko, N., Pisova, J., Exarchou, E., Havlova, I., Petrova, I., Kifnidis, K., Reis, G., Kolomyyits, S., Peterka, K., Olsr, J., Bansal, N., Nechanicky, R., Vasylets, V., Kopytsya, M., Melichar, M., Krocova, E., Machova, V., Ludka, O., Petyunina, O., Kotseruba, V., Berrouschot, J., Kvasnicka, J., Avellar, K., Kuchar, R., Kovar, P., Katz Weiand, L. Reis, Korantanis, K., Kosek, Z., Kostkova, G., Leipelt, J., Rocha, J., Ishibashi, Y., Lohman, J., Panella, M., Nozaki, T., Abi-Mansour, P., Dvoieglazova, M., Pyrgakis, V., Koval, V., Ohirko, O., Kochrt, M., Kobza, R., Koval', O., Jirmar, R., Sakamoto, S., Jerabek, O., Jelinek, Z., Jarkovsky, P., Jandik, J., Hubac, J., Honkova, M., Barros, R., Gregor, P., Rao, M., Jambula, H., Golan, L., Anzai, T., Rodrigues, L., Rocha, M. Rubia, Rodrigues, A., Rodrigues, D., dos Santos, F. Rossi, Pagnan, L. Goncalves, Sampaio, R., do Val, R., Saraiva, J., Francek, L., Florian, J., Ferkl, R., Elbl, L., Cermak, O., Burianova, H., Brtko, M., Pinto, B., and Yalcin, R.
- Subjects
Male ,medicine.medical_specialty ,Pyridines ,medicine.medical_treatment ,030204 cardiovascular system & hematology ,Brain Ischemia ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Double-Blind Method ,Recurrence ,Edoxaban ,Internal medicine ,Atrial Fibrillation ,parasitic diseases ,Secondary Prevention ,medicine ,Humans ,Myocardial infarction ,cardiovascular diseases ,Stroke ,Aged ,Advanced and Specialized Nursing ,business.industry ,Hazard ratio ,Warfarin ,Anticoagulants ,Atrial fibrillation ,Thrombolysis ,Middle Aged ,medicine.disease ,nervous system diseases ,Thiazoles ,Treatment Outcome ,chemistry ,Anesthesia ,Cardiology ,Female ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,business ,030217 neurology & neurosurgery ,TIMI ,medicine.drug - Abstract
Background and Purpose— Patients with atrial fibrillation and previous ischemic stroke (IS)/transient ischemic attack (TIA) are at high risk of recurrent cerebrovascular events despite anticoagulation. In this prespecified subgroup analysis, we compared warfarin with edoxaban in patients with versus without previous IS/TIA. Methods— ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) was a double-blind trial of 21 105 patients with atrial fibrillation randomized to warfarin (international normalized ratio, 2.0–3.0; median time-in-therapeutic range, 68.4%) versus once-daily edoxaban (higher-dose edoxaban regimen [HDER], 60/30 mg; lower-dose edoxaban regimen, 30/15 mg) with 2.8-year median follow-up. Primary end points included all stroke/systemic embolic events (efficacy) and major bleeding (safety). Because only HDER is approved, we focused on the comparison of HDER versus warfarin. Results— Of 5973 (28.3%) patients with previous IS/TIA, 67% had CHADS 2 (congestive heart failure, hypertension, age, diabetes, prior stroke/transient ischemic attack) >3 and 36% were ≥75 years. Compared with 15 132 without previous IS/TIA, patients with previous IS/TIA were at higher risk of both thromboembolism and bleeding (stroke/systemic embolic events 2.83% versus 1.42% per year; P P P P =0.02). No treatment subgroup interactions were found for primary efficacy ( P =0.86) or for intracranial hemorrhage ( P =0.28). Conclusions— Patients with atrial fibrillation with previous IS/TIA are at high risk of recurrent thromboembolism and bleeding. HDER is at least as effective and is safer than warfarin, regardless of the presence or the absence of previous IS or TIA. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00781391.
- Published
- 2016
5. Stroke and Mortality Risk in Patients With Various Patterns of Atrial Fibrillation: Results From the ENGAGE AF-TIMI 48 Trial (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48)
- Author
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Jones, D., Gu, X. J., Liu, L., Grammer, M., Waseem, M., Roper, E., Harden, M., Zellner, C., Mason, T., Zeig, S., Curtis, S., Zakhary, B., Yousuf, K., Wharton, S., VonGerichten, S., Willis, J., Dowling, C., Williams, R., Gibson, C., Williams, D., Truva, C., Westcott, J., St Laurent, B., Weiss, R., Sanchez, G., Waxman, F., Locklear, T., Ward, S., Renaud, K., Walsh, R., Kilcup, S., Vossler, M., Washam, M., Vijay, N., Warren, K., Vicari, R., Parsons, T., Verma, S., Cardoza, T., Vemireddy, D., Harrelson, K. Gonzalez, Val-Mejias, J., Hanna, K., Updegrove, J., Salas, L., Tucker, P., Romero, N., Torres, M., Southam, D., Teixeira, J., Mitchell, T., Tee, H., Young, K., Teague, S., Dastoli, K., Tawney, K., Swauger, M., Tatarko, M., Corchado, D., Tami, L., Leo, L., Talano, J., Bruton, T., Takata, T., Springer, K., Tahirkheli, N., Herwehe, S., Szulawski, I., Freemyer, D., Swerchowsky, V., Frost, J., Suresh, D., Vittitow, T., Struble, R., Cox, C., Steljes, A., Liu, M., Staniloae, C., McCartney, P., Spivack, E., Vasquez, E., Sperling, M., Thomason, L., Spangenthal, S., Hodnett, P., Smith, R., Keene, R., Smith, S., Hughes, B., Skierka, R., Nelson, M., Singh, V., Turner, K., Singh, N., Meyer, R., Simpson, P., Champagne, M., Siler, T., Stephenson, L., Shoukfeh, M., Browning, J., Shih, H., Hengerer, T., Sheikh, K., Hren, A., Shaoulian, E., Fleets, J., Shanes, J., Seese, M., Shalaby, A., Witt, P., Shah, G., Mather, N., Seide, H., Holt, A., Ullig, T., Seals, A., Mercer, S., Schulman, D., Schneider, W., Schneider, R., Fekete, A., Schaefer, S., Clifton, R., Savin, V., Lafave, J., Sandberg, J., Schomburg, J., Samal, A., Ball, E., Sacco, J., Nelson, T., Ruoff, G., Freeman, R., Ross, S., Martin, C., Rosen, R., Barnhorst, M., Rosado, J., Hollihan, P., Roehll, W., Cherrico, M., Robinson, J., Braun, D., Riofrio, K., Roberts, J., Pazier, P., Richwine, R., Stanley, E., Renzi, M., Wroblewski, J., Redondo, V., Domingo, D., Rama, P., Hemmen, C., Quinn, J., Reed, C., Quinlan, E., Rafla, E., Quadrel, M., Ebert, J., Pugeda, J., Sham, L., Pudi, K., Lowe, K., Pribble, A., Neeper, L., Pratt, R., Cush, S., Poulathas, A., Kirk, D., Yovaniniz, P., Pezzella, S., Brown, F., Pettis, K., Morlando, F., Petruzziello, F., Chacon, L., Peters, P., Duncan, D., Pentz, W., Montayne, S., Pearlstein, R., Gorry, N., Pavon, H., Dennison, K., Patnam, S., Joseph, L., Oza, S., Gonzalez, M., Osborne, J., Garcia, L., Orchard, R., McCormick, J., Oppenheimer, K., Thakkar, N., Oberoi, M., Wilmot, M., Nielsen, R., Nomanee, S., Nguyen, T., Goza, J., Nallasivan, M., West, M., Naidu, J., Parker, A., Nadar, V., Oehmann, V., Murphy, A., Raziano, S., Mullen, P., Todd, S., Mowdy, M., Schuler, C., Mounsey, P., Parrott, N., Mouhaffel, A., Bowman, B., Morledge, J., Garner, S., Moran, J., Strugatsky, S., Mody, F., Gryczan, J., Miller, S., Sanchez, S., Miller, R., Sanders, D., Milas, J., Romero-Colon, J., Michlin, B., Cajulis, C., Mercado, A., Cervellione, K., Mendelson, R., Wall, J., Mehrle, A., Skinner, J., Meholick, A., Marti, J., Mega, J., Lack, A., McLaurin, B., Paul, J., McKnight, T., Rodkey, K., McKenzie, M., Miranda, J., McGuire, K., Schwarz, L., McGarvey, J., Stubbs, L., McCartney, M., Hicks, T., Massin, E., Bedenko, E., Marenberg, M., Rabadi-Marar, D., Marar, I., Hernandez, S., Mandviwala, M., Casas, R., Makam, S., Lisiecki, B., Mainigi, S., Doctor, A., Magee, A., Bush, D., Macomber, J., Edelstein, J., Lurie, M., Wright, H., Lui, H., Ault, S., Looby, R., Davids, M., Lone, B., Shah, D., Lomnitz, D., Wofford, E., Littlefield, R., Murphy, R., Ling, L., Miller, D., Lillestol, M., Bonds, C., Lewis, D., Hartley, L., Lesser, M., Smith, D., Lentz, M., Royse, H., Ledbetter, L., Faucett, S., Langevin, E., Simmons, T., Lang, J., Ferguson, D., Landau, C., Coyle, G. 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- Subjects
Male ,medicine.medical_specialty ,medicine.drug_mechanism_of_action ,Pyridines ,medicine.medical_treatment ,Factor Xa Inhibitor ,Hemorrhage ,030204 cardiovascular system & hematology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Edoxaban ,Risk Factors ,Physiology (medical) ,Internal medicine ,Thromboembolism ,Atrial Fibrillation ,Medicine ,Humans ,atrial fibrillation ,cardiovascular diseases ,030212 general & internal medicine ,Myocardial infarction ,Stroke ,Aged ,business.industry ,Warfarin ,Anticoagulants ,Atrial fibrillation ,Thrombolysis ,thromboembolism ,bleeding ,medicine.disease ,mortality ,stroke ,Thiazoles ,Treatment Outcome ,chemistry ,Anesthesia ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business ,TIMI ,medicine.drug ,Factor Xa Inhibitors - Abstract
Background— Whether the pattern of atrial fibrillation (AF) modifies the risk/benefit of anticoagulation is controversial. In ENGAGE AF-TIMI 48 trial (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial Infarction 48), the factor Xa inhibitor edoxaban was noninferior to warfarin in preventing stroke or systemic embolic events and significantly reduced bleeding and cardiovascular mortality. However, detailed analyses by AF pattern have not been reported. Methods and Results— The 21 105 patients were categorized as having paroxysmal (P -adj =0.015) and permanent AF (1.95%/year; P -adj =0.004). Overall, all-cause mortality also was lower with paroxysmal (3.0%/year) compared with persistent (4.4%/year; P -adj P -adj Conclusions— In ENGAGE AF-TIMI 48 trial, patients with paroxysmal AF suffered fewer thromboembolic events and deaths compared with those with persistent and permanent AF. The efficacy and safety profile of edoxaban as compared with warfarin was consistent across the 3 patterns of AF. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00781391.
- Published
- 2016
6. Cerebrovascular events in 21 105 patients with atrial fibrillation randomized to edoxaban versus warfarin: Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48
- Author
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Dougal, K., Venkataraman, A., Murdoch, D., Blagden, M., Dunn, S., MacCallum, P., Young, G., Lip, G., Senior, R., Brown, R., Sopher, M., Ebano, P., Linker, N., Atkinson, C., Lindsay, S., MacLeod, M., More, R., Ramasamy, V., Chapman, O., Lie, F., Beeton, I., McGhee, C., Wilmott, R., Dickinson, D., Douglas, H., Davies, D., D'Costa, D., Finlayson, M., Wright, A., Avery, D., Wright, L., Pye, M., Marazzi, P., Flint, L., Newby, D., Kennard, S., Andrews, A., Storey, R., Helliwell, L., Bridge, C., Choy, A., Turner, W., Walker, M., Wright, J., Smith, S., Jones, D., Maxwell, T., Chung, A., Isted, C., Cohen, A., Camm, J., Price, R., Watkin, R., Gilchrist, M., Duff, J., Aggarwal, R., Eldred, R., Adler, P., Chehayeb, R., Vandekerckhove, Y., Gordon, L., Jones, S., Young, C., Coyle, G. Stagi, Ferguson, D., Lang, J., Simmons, T., Langevin, E., Faucett, S., Ledbetter, L., Royse, H., Lentz, M., Smith, D., Lesser, M., Hartley, L., Lewis, D., Bonds, C., Lillestol, M., Miller, D., Ling, L., Murphy, R., Littlefield, R., Wofford, E., Lomnitz, D., Shah, D., Lone, B., Davids, M., Looby, R., Ault, S., Lui, H., Wright, H., Lurie, M., Edelstein, J., Macomber, J., Bush, D., Magee, A., Doctor, A., Mainigi, S., Lisiecki, B., Makam, S., Casas, R., Mandviwala, M., Hernandez, S., Marar, I., Rabadi-Marar, D., Marenberg, M., Bedenko, E., Massin, E., Hicks, T., McCartney, M., Stubbs, L., McGarvey, J., Schwarz, L., McGuire, K., Miranda, J., McKenzie, M., Rodkey, K., McKnight, T., Paul, J., McLaurin, B., Lack, A., Mega, J., Marti, J., Meholick, A., Skinner, J., Mehrle, A., Wall, J., Mendelson, R., Cervellione, K., Mercado, A., Cajulis, C., Michlin, B., Romero-Colon, J., Milas, J., Sanders, D., Miller, R., Sanchez, S., Miller, S., Gryczan, J., Mody, F., Strugatsky, S., Moran, J., Garner, S., Morledge, J., Bowman, B., Mouhaffel, A., Parrott, N., Mounsey, P., Schuler, C., Mowdy, M., Todd, S., Mullen, P., Raziano, S., Murphy, A., Oehmann, V., Nadar, V., Parker, A., Naidu, J., West, M., Nallasivan, M., Goza, J., Nguyen, T., Nomanee, S., Nielsen, R., Wilmot, M., Oberoi, M., Thakkar, N., Oppenheimer, K., McCormick, J., Orchard, R., Garcia, L., Osborne, J., Gonzalez, M., Oza, S., Joseph, L., Patnam, S., Dennison, K., Pavon, H., Gorry, N., Pearlstein, R., Montayne, S., Pentz, W., Duncan, D., Peters, P., Chacon, L., Petruzziello, F., Morlando, F., Pettis, K., Brown, F., Pezzella, S., Kirk, D., Poulathas, A., Cush, S., Pratt, R., Neeper, L., Pribble, A., Lowe, K., Pudi, K., Sham, L., Pugeda, J., Ebert, J., Quadrel, M., Rafla, E., Quinlan, E., Reed, C., Quinn, J., Hemmen, C., Rama, P., Domingo, D., Redondo, V., Wroblewski, J., Renzi, M., Stanley, E., Richwine, R., Pazier, P., Roberts, J., Riofrio, K., Braun, D., Robinson, J., Cherrico, M., Roehll, W., Hollihan, P., Rosado, J., Barnhorst, M., Rosen, R., Martin, C., Ross, S., Freeman, R., Ruoff, G., Nelson, T., Sacco, J., Ball, E., Samal, A., Schomburg, J., Sandberg, J., Lafave, J., Savin, V., Clifton, R., Schaefer, S., Fekete, A., Schneider, R., Schneider, W., Schulman, D., Mercer, S., Seals, A., Ullig, T., Holt, A., Seide, H., Mather, N., Shah, G., Witt, P., Shalaby, A., Seese, M., Shanes, J., Fleets, J., Shaoulian, E., Hren, A., Sheikh, K., Hengerer, T., Shih, H., Browning, J., Shoukfeh, M., Stephenson, L., Siler, T., Champagne, M., Simpson, P., Meyer, R., Singh, N., Turner, K., Singh, V., Nelson, M., Skierka, R., Hughes, B., Keene, R., Smith, R., Hodnett, P., Spangenthal, S., Thomason, L., Sperling, M., Vasquez, E., Spivack, E., McCartney, P., Staniloae, C., Liu, M., Steljes, A., Cox, C., Struble, R., Vittitow, T., Suresh, D., Frost, J., Swerchowsky, V., Freemyer, D., Szulawski, I., Herwehe, S., Tahirkheli, N., Springer, K., Takata, T., Bruton, T., Talano, J., Leo, L., Tami, L., Corchado, D., Tatarko, M., Swauger, M., Tawney, K., Dastoli, K., Teague, S., Young, K., Tee, H., Mitchell, T., Teixeira, J., Southam, D., Torres, M., Romero, N., Tucker, P., Salas, L., Updegrove, J., Hanna, K., Val-Mejias, J., Harrelson, K. Gonzalez, Vemireddy, D., Cardoza, T., Verma, S., Parsons, T., Vicari, R., Warren, K., Vijay, N., Washam, M., Vossler, M., Kilcup, S., Walsh, R., Renaud, K., Ward, S., Locklear, T., Waxman, F., Sanchez, G., Weiss, R., St Laurent, B., Westcott, J., Truva, C., Williams, D., Gibson, C., Williams, R., Dowling, C., Willis, J., VonGerichten, S., Wood, K., Capasso-Gulve, E., Worley, S., Pointer, S., Yarows, S., Sheehan, T., Yasin, M., Preston, S., Yi, J., Dongas, B., Yousuf, K., Fisher, M., Zakhary, B., Curtis, S., Zeig, S., Mason, T., Zellner, C., Harden, M., Roper, E., Waseem, M., Grammer, M., Ruff, Christian T., Giugliano, Robert P., Beerts, C., Vrolix, M., Mestdagh, I., Vervoort, G., van Welden, J., Vanwelden, J., Derycker, K., Jacobs, C., Stockman, D., Huyberechts, D., Scavee, C., Clinckemaille, N., Parque, J., Raepers, M., Mairesse, G., Malmendier, D., Herzet, J., Meeusen, K., Heidbuchel, H., Tincani, G., Desfontaines, P., De Bruyne, L., De Tollenaere, M., de Koning, K., De Bleecker, J., 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Vogelmann, O., Braunwald, Eugene, Antman, Elliott M., Mercuri, Michele, Shi, Minggao, Dave, Jay, Duggal, Anil, Betcher, Joshua M., Grip, Laura T., Murphy, Sabina A., Deenadayalu, Naveen, Lowe, Cheryl, Wiviott, Stephen D., Silverman, Scott, Gowda, S., Rafala, E., Graham, S., Bonora, M., Griffin, S., Aull, L., Griffin, J., Goodman, V., Grossman, C., Davis, A., Grove, D., Mabe, K., Guarino, J., Gabela, W., Guarnieri, T., Guerrero, Guerrero, Foster, B., Guthrie, R., Felsman, D., Gvora, T., McLean, R., Rost, Natalia S., Hack, T., Morelli, L., Hamroff, G., Bentivenga, L., Han, M., Cavanna, L., Harris, J., Bobade, M., Hearne, S., Krater, C., Heiman, M., Dandekar, U., Henderson, D., Millard, D., Henry, S., Harkins, V., Hermany, P., Batchell, K., Herrod, J., Miranda, D., Herson, S., Carey, G., Hinchman, D., Vieira, P., Hippert, R., Dutter, S., Hoekstra, J., Homan, J., Homayouni, A., Horton, K., Sloss, D., Hotchkiss, D., Turner, N., Houchin, V., Adams, K., Howard, V., Hays, D., Howard, L., 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Altonen, D., Barber, M., Campbell, G., Baman, R., Batista, M., Baine, S., Thompson, B., Ayesu, K., Baldwin, E., Awasty, V., Cobos, D., Aude, Y., Strickland, S., Attanti, S., Rasmussen, L., Arouni, A., Shoaf, R., Arnold, T., York, T., Anderson, J., Persechino, F., Amin, M., Khetarpal, S., Amin, K., Lane, B., Alsheikh, T., MacDonald, H., Almquist, A., Biscardi, R., Allison, J., Godsey, W., Aliyar, P., Genova-Peeva, E., Desai, A., Alexander, J., Brubaker, S., Akhter, F., Lim, G., Ahmadpour, H., Hussain, A., Ahmad, A., Beck, P., Reiling, S., Barash, B., Adler, J., Lohman, J., Panella, M., Abi-Mansour, P., Mackin, A., Moriarty, A., Green, M., Shandra, T., Zhurba, S., Logvinov, Y., Zharinov, O., Mudruk, I., Yena, L., Nahrebetskyy, V., Yagensky, A., Serik, S., Volkov, V., Goncharov, O., Vizir, V., Sklyanna, O., Vatutin, M., Drapchak, I., Vakaliuk, I., Steward, A., Desire, A., Waters, L., Tykhonova, S., Kuznetsov, I., Tseluyko, V., Lyzohub, S., Sychov, O., Perebetiuk, L., Stanislavchuk, M., 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J., Qiu, Y., Hong, L., You, Z. G., Hong, K., Zhang, P., Fu, G. S., Feng, C., Dong, Y. G., Zhang, X., Chen, X. P., Xie, X. D., Chen, J. Z., Xu, G. L., Bai, F., Grandon Azua, M., Yovaniniz, P., Lara Lara, C., Stockins, B., Campisto, Y., Zapata Staub, J., Potthoff, S., Torres Carrasco, G., Pincetti, C., Carmona Perez, M., Opazo, M., Romero Llamas, R., Martinez, D., Manriquez Silva, L., Manriquez, L., Rebolledo, C., Lopetegui, M., Arratia Diaz, P., Florenzano, F., Parada, A., Corbalan, R., Obreque, C., Cobos, J., Mondaca Mondaca, P., Bugueno, C., Retamal Matus, L., Balboa, W., Mabee, J., Woodford, T., Caterini, T., Wharton, S., Morley, A., Wahby, R., Giesbrecht, L., Velthuysen, G., Teitelbaum, J., Teitelbaum, I., Tremblay, M., Talbot, P., David, D., Talajic, M., Bobbie, C., Syan, G., Kailey, P., Sussman, J., Morissette, A., St-Hilaire, R., Silverio, G., Shu, D., Marchand, C., Rupka, D., Bozek, B., Ricci, J., Nethercott, C., Qureshi, A., Turri, L., Polasek, P., Sardin, V., Pesant, Y., Carroll, L., Parkash, R., Bolton, R., O'Mahony, W., Banville, P., O'Hara, G., Nicholson, R., Lamoureux, U., Garb, J., Najarali, A., Krider, J., Mucha, M., Roth, M., Morrison, D., Morely, A., Mawji, A., Studenikow, E., Maranda, C., Vaillancourt, T., Malette, P., Matthews, J., MacCallum, C., Seib, M., Ma, P., Douglas, S., Luton, R., Roberts, P., Lichtenstein, T., Lam, H., Lam, S., St-Germain, L., Lainesse, A., Dewar, C., Labonte, R., Roy, M., Kouz, S., Perkins, L., Huynh, T., Standring, R., Hoag, G., Ho, V., Ho, K., Scott, L., Heath, J., Hatheway, R., Houbraken, D., Viau, C., Fortin, C., Zondag, M., Eikelboom, J., Dufresne, M., Kubanska, A., du Preez, M., Denis, I., Coutu, B., Masson, C., Costi, P., Gauthier, M., Constance, C., Valley, S., Cleveland, D., Vansickle, L., Chilvers, M., Lepage, C., Otis, J., Cha, J., Hundseth, M., Bose, S., Stafford, C., Bhargava, R., Antle, S., Archibald, J., Manoylov, E., Kitova, M., Tzekova, M., Tumbeva, D., Tumbev, H., Nyagina, M., Todorov, G., Momchilova-Lozeva, D., Staneva, A., Vasilev, I., Popov, A., Milusheva, T., Petranov, S., Kostov, K., Pencheva, G., Vasilev, D., Nikolov, F., Stoyanovski, V., Mincheva, V., Miteva, B., Mihov, A., Manolova, A., Kamenova, P., Hergeldjieva, V., Kinova, E., Goudev, A., Kostova, E., Georgiev, B., Gergova, V., Donova, T., Milcheva, N., Denchev, S., Parishev, G., Chompalova, B., Zimmermann, E. Burger, Zimmermann, S., Almeida, M., Boas, F. Villas, Lustosa, E., Sobral Filho, D., Carraro, A., Simoes, M., Vicente, C., Saraiva, J., do Val, R., Sampaio, R., Pagnan, L. Goncalves, dos Santos, F. Rossi, Rodrigues, D., Rodrigues, A., Rocha, M. Rubia, Rodrigues, L., Barros, R., Rocha, J., Leipelt, J., Katz Weiand, L. Reis, Avellar, K., Reis, G., Gozalo, A., Almeida, J. Pimenta, Luiz, R. Osorio, Leaes, P., Morales, K., Sebba Barroso de Souza, W. Kunz, Radaelli, G., Kalil, C., Almeida, A., Kaiser, S., Cury, C., Jorge, J., Pereira, L., Jaeger, C., Ninho, L., Guimaraes, A., Gomes, A., Gomes, M., Pereira, G., Gagliardi, R., Daitz, C., Finimundi, H., Araujo, E., Ferreira, L., Seroqui, M., Saporito, W. Faustino, Morgado, S., Dutra, O., Laimer, R., Duda, N., Pereira, V., De Patta, M., Barroso, D., Costantini, C., Silva, J., Chaves Junior, H., Fleck, N., Brondani, R., Cunha, S., Botelho, R., Sehnem, E., Precoma, D. Bertolim, Ferraz, R. Franchin, Alves da Costa, F. Augusto, Motta, C., Atie, J., de Melo, R. Ferreira, Lotufo, P. Andrade, Coutinho, E., Vincenzo de Paola, A. Amato, Denie, D., and Wollaert, B.
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Male ,medicine.medical_specialty ,medicine.drug_mechanism_of_action ,medicine.drug_class ,Pyridines ,Factor Xa Inhibitor ,Infarction ,chemistry.chemical_compound ,Double-Blind Method ,Edoxaban ,Internal medicine ,Atrial Fibrillation ,medicine ,Humans ,Myocardial infarction ,cardiovascular diseases ,Stroke ,Aged ,Advanced and Specialized Nursing ,Dose-Response Relationship, Drug ,business.industry ,Anticoagulant ,Warfarin ,Anticoagulants ,Atrial fibrillation ,Middle Aged ,medicine.disease ,Thiazoles ,Treatment Outcome ,chemistry ,Anesthesia ,Cardiology ,Female ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug - Abstract
Background and Purpose— The once-daily oral factor Xa inhibitor, edoxaban, is as effective as warfarin in preventing stroke and systemic embolism while decreasing bleeding in a phase III trial of patients with atrial fibrillation at moderate–high stroke risk. Limited data regarding cerebrovascular events with edoxaban were reported previously. Methods— We analyzed the subtypes of cerebrovascular events in 21 105 patients participating in Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48) comparing outcomes among patients randomized to warfarin versus 2 edoxaban regimens (high dose, low dose). The primary end point for this prespecified analysis of cerebrovascular events was all stroke (ischemic plus hemorrhagic), defined as an abrupt onset of focal neurological deficit because of infarction or bleeding with symptoms lasting ≥24 hours or fatal in Results— Patients randomized to high-dose edoxaban had fewer strokes on-treatment (hazard ratio, 0.80; 95% confidence interval, 0.65–0.98) than warfarin (median time-in-therapeutic range, 68.4%); patients in the low-dose edoxaban group had similar rates (hazard ratio, 1.10 versus warfarin; 95% confidence interval, 0.91–1.32). Rates of ischemic stroke or transient ischemic attack were similar with high-dose edoxaban (1.76% per year) and warfarin (1.73% per year; P =0.81), but more frequent with low-dose edoxaban (2.48% per year; P Conclusions— In patients with atrial fibrillation, once-daily edoxaban was as effective as warfarin in preventing all strokes, with significant reductions in various subtypes of intracranial bleeding. Ischemic cerebrovascular event rates were similar with high-dose edoxaban and warfarin, whereas low-dose edoxaban was less effective than warfarin. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00781391.
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- 2014
7. Quantitative Electroencephalography of Medetomidine, Medetomidine‐Midazolam and Medetomidine‐Midazolam‐Butorphanol in Dogs
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ITAMOTO, K., primary, TAURA, Y., additional, WADA, N., additional, TAKUMA, T., additional, UNE, S., additional, NAKAICHI, M., additional, and HIKASA, Y., additional
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- 2002
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8. Effect of Medetomidine on Electroencephalography and Use of a Quantitative Electroencephalograph for Evaluating Sedation Levels in Dogs
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Itamoto, K., primary, Taura, Y., additional, Wada, N., additional, Taga, A., additional, Takuma, T., additional, Matsumura, H., additional, and Miyara, T., additional
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- 2001
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9. Anaesthetic and Cardiopulmonary Effects of Balanced Anaesthesia with Medetomidine-Midazolam and Butorphanol in Dogs
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Itamoto, K., primary, Hikasa, Y., additional, Sakonjyu, I., additional, Itoh, H., additional, Kakuta, T., additional, and Takase, K., additional
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- 2000
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10. Effects of low-level laser irradiation on canine fibroblasts.
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Purba MS, Anggoro D, Itoh H, Itamoto K, Nemoto Y, Nakaichi M, Sunahara H, and Tani K
- Abstract
Low-level laser (LLL) therapy is a well-known noninvasive treatment that stimulates fibroblasts to improve wound healing. LLL can improve fibroblast proliferation and migration without causing toxicity. The present study aimed to evaluate the effects of two laser wavelengths at different irradiation times on canine fibroblasts. Fibroblasts were isolated from canine oral mucosa. After seeding for 24 hr, the fibroblasts were irradiated using the Erchonia
®️ EVL dual-diode laser at wavelengths of 405 nm (5 mW) and 640 nm (7.5 mW) with irradiation times of 120, 360, and 1,800 sec. The proliferating and viability cells were evaluated 24 hr after laser irradiation. Wound closure rates were calculated at 0, 24, and 48 hr after laser irradiation. Parameters, including proliferation cell, cell viability, and cell migration, tended to be higher in the 360-sec group (405 nm) and 120-sec group (640 nm) than in other groups. Our findings suggest that LLL therapy at wavelengths of 405 and 640 nm with an irradiation time of 120-360 sec (0.26-0.51 J/cm2 ) can stimulate the proliferation and migration of canine fibroblasts. This finding may contribute to a better understanding of the beneficial role of LLL stimulation in canine wound healing.- Published
- 2024
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11. The perfusion index as a method of assessing epidural anaesthesia efficacy in healthy dogs.
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Itoh H, Inoue H, Itamoto T, Tani K, Sunahara H, Nemoto Y, Nakaichi M, Iseri T, and Itamoto K
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Introduction: Perfusion index (PI) is used as assessment of epidural anaesthesia efficacy in human medicine, but its usefulness in dogs is unknown. The aim of this study was to evaluate the usefulness of PI in determining epidural anaesthesia effectiveness., Material and Methods: This is prospective cross-over experimental study. Five healthy adult beagle dogs were anaesthetised and an epidural catheter was inserted in the lumbosacral area and adjusted so that the end of the catheter was placed at the fourth lumbar vertebra. Single-port catheters were used in the control group and multiple-port catheters were used in the treatment group. A PI probe was placed on a hind leg, and the catheter placement was confirmed via computed tomography. The treatment group received a bolus dose of lidocaine, and the control group received saline, via epidural catheter. The PI value was recorded every 5 min until 30 min after lidocaine injection., Results: The PIs of the hind limbs were not significantly different over time, nor were they between the control and lidocaine-injected groups at any point in time., Conclusion: The PI is not useful in determining the efficacy of epidural anaesthesia in dogs under general anaesthesia. In the future, finding a reliable method to evaluate the success of regional anaesthesia, even in patients under general anaesthesia, will be necessary., Competing Interests: Conflict of Interests Statement: The authors declare that there is no conflict of interests regarding the publication of this article., (© 2024 Harumichi Itoh et al., published by Sciendo.)
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- 2024
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12. Two illustrative cases of traumatic intracranial cerebral artery dissection in children.
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Hokari M, Shimbo D, Uchida K, Asaoka K, Ajiki M, Itamoto K, and Takada T
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Traumatic intracranial cerebral artery dissection (ICAD) in the pediatric population is relatively rare. We report two traumatic ICAD cases in children. Case 1: A 13-year-old boy presented with headache and left hemiparesis after body contact while playing basketball. We found a cerebral infarction in the middle cerebral artery territory and dissection at the bifurcation of the right internal carotid artery and posterior communicating artery. Six days after onset, his right hemiparesis deteriorated, and the infarction progressed. Therefore, bypass surgery was performed. Three months later, he regained the ability to walk without a cane and resumed school. Case 2: A 10-year-old boy fell while skiing and experienced a severe headache several hours later. Neuroradiological examination revealed a subarachnoid hemorrhage in the basal cistern without aneurysm. Six days after admission, magnetic resonance angiography revealed stenotic changes and an irregularly shaped basilar artery (BA). On day 7, an angiogram confirmed BA dissection. The patient's headache gradually improved, and the irregular shape of the BA normalized 3 weeks later. He was discharged without any neurological deficits. Determining whether vascular reconstruction should be performed is challenging. However, we believe that therapeutic intervention should be performed promptly when symptoms or brain images deteriorate., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)
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- 2024
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13. Elucidation of the radius and ulna fracture mechanisms in toy poodle dogs using finite element analysis.
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Anggoro D, Purba MS, Jiang F, Nishida N, Itoh H, Itamoto K, Nemoto Y, Nakaichi M, Sunahara H, and Tani K
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- Animals, Dogs physiology, Biomechanical Phenomena, Forelimb physiology, Tomography, X-Ray Computed veterinary, Stress, Mechanical, Finite Element Analysis, Ulna Fractures veterinary, Ulna Fractures diagnostic imaging, Radius Fractures veterinary
- Abstract
Fractures occurring in the distal radius and ulna of toy breed dogs pose distinctive challenges for veterinary practitioners, requiring specialized treatment approaches primarily based on anatomical features. Finite Element Analysis (FEA) was applied to conduct numerical experiments to determine stress distribution across the bone. This methodology offers an alternative substitute for directly investigating these phenomena in living dog experiments, which could present ethical obstacles. A three-dimensional bone model of the metacarpal, carpal, radius, ulna, and humerus was reconstructed from Computed Tomography (CT) images of the toy poodle and dachshund forelimb. The model was designed to simulate the jumping and landing conditions from a vertical distance of 40 cm to the ground within a limited timeframe. The investigation revealed considerable variations in stress distribution patterns between the radius and ulna of toy poodles and dachshunds, indicating notably elevated stress levels in toy poodles compared to dachshunds. In static and dynamic stress analysis, toy poodles exhibit peak stress levels at the distal radius and ulna. The Von Mises stresses for toy poodles reach 90.07 MPa (static) and 1,090.75 MPa (dynamic) at the radius and 1,677.97 MPa (static) and 1,047.98 MPa (dynamic) at the ulna. Conversely, dachshunds demonstrate lower stress levels for 5.39 MPa (static) and 231.79 MPa (dynamic) at the radius and 390.56 MPa (static) and 513.28 MPa (dynamic) at the ulna. The findings offer valuable insights for modified treatment approaches in managing fractures in toy breed dogs, optimizing care and outcomes.
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- 2024
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14. Finite element study on post-screw removal stress in toy poodle radius with different plate designs and screw arrangements.
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Anggoro D, Purba MS, Jiang F, Nishida N, Itoh H, Itamoto K, Nemoto Y, Nakaichi M, Sunahara H, and Tani K
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- Animals, Biomechanical Phenomena, Stress, Mechanical, Radius surgery, Forelimb, Tomography, X-Ray Computed veterinary, Finite Element Analysis, Bone Screws veterinary, Bone Screws adverse effects, Bone Plates veterinary
- Abstract
Background: The study employs finite element analysis to investigate stress distribution in the radius of toy poodles after screw removal. The examination focuses on the biomechanical implications of varied screw hole configurations using 1.5 and 2.0-mm locking compression plates (LCPs) with notched head T-Plates., Aim: To provide a noninvasive approach to analyzing the immediate consequences of screw removal from the radius bone in toy poodles. Specifically, it explores the impact of varied plate designs and screw arrangements on stress distribution within the forelimb bones., Methods: The study constructs a three-dimensional bone model of the toy poodle's forelimb based on computed tomography (CT) images. Simulations were designed to replicate jumping and landing from a 40 cm height, comparing stress distribution in the radius post-screw removal., Results: The analysis reveals significant variations in stress distribution patterns between the two LCPs. The radius implanted with the 2.0-mm LCP displays a uniform stress distribution, contrasting with the 1.5-mm plates. Localized stress concentration is observed around the screw holes, while trabecular bone regions near the screw holes exhibit lower stress levels., Conclusion: The study highlights the plate designs and screw configurations that affect bone stress in toy poodle forelimbs post-screw removal. The findings provide valuable insights for veterinarians, aiding informed decisions in veterinary orthopedic practices., Competing Interests: The authors declare that there is no conflict of interest.
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- 2024
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15. Suspected malnutrition-induced reversible feline skin fragility syndrome in a cat with congenital axial deformities.
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Yu Y, Miyamoto T, Kimura Y, Itamoto K, Michishita M, Hatakeyama H, Nagashima T, Asada R, Yamaguchi T, Hasegawa D, Nomura Y, Lyons LA, and Kosho T
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- Female, Cats, Animals, Ataxia veterinary, Biopsy veterinary, Scoliosis veterinary, Malnutrition veterinary, Cat Diseases diagnosis, Cat Diseases etiology
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A stray cat, an intact female Japanese domestic shorthair cat of unknown age (suspected to be a young adult), was rescued. The cat was lethargic and thin and had marked skin fragility, delayed wound healing without skin hyperextensibility, and hind limb proprioceptive ataxia and paresis. Survey radiography, computed tomography, and magnetic resonance imaging revealed congenital vertebral anomalies, including thoracolumbar transitional vertebrae, scoliosis resulting from a thoracic lateral wedge-shaped vertebra, and a kinked tail, and a dilated spinal cord central canal. Through nutritional support, the cat's general condition normalized, followed by a gradual and complete improvement of skin features. Whole-genome sequencing was completed; however, no pathogenic genetic variant was identified that could have caused this phenotype, including congenital scoliosis. A skin biopsy obtained 7 y after the rescue revealed no remarkable findings on histopathology or transmission electron microscopy. Based on clinical course and microscopic findings, malnutrition-induced reversible feline skin fragility syndrome (FSFS) was suspected, and nutritional support was considered to have improved the skin condition. Key clinical message: This is the second reported case of presumed malnutrition-induced reversible FSFS and was accompanied by long-term follow-up., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)
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- 2024
16. Relationship between clinical parameters and malformations in dogs diagnosed with atlanto-axial instability.
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Itoh H, Itamoto T, Tani K, Sunahara H, Nemoto Y, Nakaichi M, Iseri T, Horikirizono H, and Itamoto K
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- Humans, Dogs, Animals, Retrospective Studies, Physical Examination, Body Weight, Dog Diseases diagnostic imaging, Dog Diseases epidemiology, Dog Diseases congenital, Syringomyelia diagnostic imaging, Syringomyelia epidemiology, Syringomyelia veterinary, Atlanto-Axial Joint diagnostic imaging
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Atlanto-axial instability is a common disease that affects toy-breed dogs. Most cases of atlanto-axial instability are congenital. Furthermore, patients with atlanto-axial instability are predisposed to other concurrent diseases. Therefore, this study aimed to retrospectively determine the presence of concurrent diseases in cases with atlanto-axial instability using imaging data and analyze the relationship between clinical parameters and the incidence of complex malformations. The clinical data and imaging findings of 41 toy-breed dogs diagnosed with atlanto-axial instability were analyzed using their medical records and imaging data. Occipital dysplasia (17/27), atlanto-occipital overlapping (22/34), dens dysplasia (27/41), Chiari-like malformation (8/34), syringomyelia (5/34), lateral ventricular enlargement (20/36), and intracranial arachnoid cyst (5/35) were observed in patients with atlanto-axial instability. The body weight of the patients in the groups with atlanto-occipital overlapping and lateral ventricular enlargement was lower than that of those in the groups without these diseases (1.78 ± 0.71 vs 2.71 ± 1.15 kg, P = 0.0269, 1.60 ± 0.40 vs 2.75 ± 1.08 kg, P = 0.001, respectively). Furthermore, when the correlation between the total number of concurrent diseases and the age at onset and body weight was examined, it became clear that lower body weight was associated with the incidence of a greater number of concurrent diseases. Thus, the findings of this study suggest that toy-breed dogs are more likely to present with complex malformations and should be evaluated carefully with additional examinations and treatment methods., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Itoh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2024
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17. Quantitative evaluation of the biomechanical and viscoelastic properties of the dog patellar tendon in response to neuromuscular blockade at different stifle angles.
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Anggoro D, Purba MS, Nishida N, Itoh H, Itamoto K, Nemoto Y, Nakaichi M, Sunahara H, and Tani K
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- Dogs, Animals, Female, Humans, Stifle physiology, Rocuronium pharmacology, Knee Joint, Biomechanical Phenomena, Patellar Ligament physiology, Neuromuscular Blockade
- Abstract
The patellar tendon (PT) is crucial for maintaining stability and facilitating movement in the stifle joint. Elastography has been recognized as a prominent method for evaluating PT properties in humans and dogs. The utilization of oscillation methods in canine studies remains limited despite their extensive documentation in human studies. Our study represents the first effort to quantitatively assess and compare the effects of muscle relaxant on the biomechanical and viscoelastic characteristics of the PT at varying stifle angles in living dogs. Five healthy female beagles were used in this study. Biomechanical (tone, stiffness, and decrement) and viscoelastic (relaxation time and creep) properties of the PT were measured using MyotonPRO (Myoton Ltd, Estonia) prior to and following administration of rocuronium (0.5 mg/kg/body weight) at normal, extended, and flexed positions. Rocuronium was selected for its safety, controllability, and widespread clinical use in veterinary anesthesia. Two-way analysis of variance showed that tone, stiffness, and decrement were significantly higher (P < 0.001) in the control group than in the muscle relaxation group. At the same time, relaxation time and creep were significantly lower (P < 0.001) in the control group than in the muscle relaxation group. The findings indicate that stifle angle position and muscle rexalant administration fundamentally alter the biomechanical loading conditions of the PT, leading to changes in its viscoelastic properties. Therefore, this novel quantitative data could benefit clinical settings that necessitate accurate and objective methods for risk identification and monitoring PT biomechanics in dogs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Anggoro et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2024
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18. Proof-of-concept study of the caninized anti-canine programmed death 1 antibody in dogs with advanced non-oral malignant melanoma solid tumors.
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Igase M, Inanaga S, Nishibori S, Itamoto K, Sunahara H, Nemoto Y, Tani K, Horikirizono H, Nakaichi M, Baba K, Kambayashi S, Okuda M, Sakai Y, Sakurai M, Kato M, Tsukui T, and Mizuno T
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- Dogs, Animals, Humans, Programmed Cell Death 1 Receptor, Treatment Outcome, Melanoma drug therapy, Melanoma veterinary, Melanoma pathology, Skin Neoplasms drug therapy, Skin Neoplasms veterinary, Skin Neoplasms pathology, Dog Diseases drug therapy
- Abstract
Background: The anti-programmed death 1 (PD-1) antibody has led to durable clinical responses in a wide variety of human tumors. We have previously developed the caninized anti-canine PD-1 antibody (ca-4F12-E6) and evaluated its therapeutic properties in dogs with advance-staged oral malignant melanoma (OMM), however, their therapeutic effects on other types of canine tumors remain unclear., Objective: The present clinical study was carried out to evaluate the safety profile and clinical efficacy of ca-4F12-E6 in dogs with advanced solid tumors except for OMM., Methods: Thirty-eight dogs with non-OMM solid tumors were enrolled prospectively and treated with ca-4F12-E6 at 3 mg/kg every 2 weeks of each 10-week treatment cycle. Adverse events (AEs) and treatment efficacy were graded based on the criteria established by the Veterinary Cooperative Oncology Group., Results: One dog was withdrawn, and thirty-seven dogs were evaluated for the safety and efficacy of ca-4F12-E6. Treatment-related AEs of any grade occurred in 13 out of 37 cases (35.1%). Two dogs with sterile nodular panniculitis and one with myasthenia gravis and hypothyroidism were suspected of immune-related AEs. In 30 out of 37 dogs that had target tumor lesions, the overall response and clinical benefit rates were 6.9% and 27.6%, respectively. The median progression-free survival and overall survival time were 70 days and 215 days, respectively., Conclusions: The present study demonstrated that ca-4F12-E6 was well-tolerated in non-OMM dogs, with a small number of cases showing objective responses. This provides evidence supporting large-scale clinical trials of anti-PD-1 antibody therapy in dogs., Competing Interests: Takuya Mizuno received research funding from Nippon Zenyaku Kogyo Co., Ltd. The remaining authors declare no conflicts of interest., (© 2024 The Korean Society of Veterinary Science.)
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- 2024
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19. Sulfasalazine, a potent cystine-glutamate transporter inhibitor, enhances osteogenic differentiation of canine adipose-derived stem cells.
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Itoh H, Tani K, Sunahara H, Nemoto Y, Nakaichi M, Horikirizono H, and Itamoto K
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- Animals, Dogs, Cystine, Cell Differentiation, Glutathione, Amino Acid Transport System X-AG, Stem Cells, RNA, Messenger, Sulfasalazine pharmacology, Osteogenesis
- Abstract
Cystine-glutamate transporter (xCT) is a plasma membrane transporter that imports cystine and indirectly contributes to the oxidative stress resistance associated with increased intracellular glutathione levels. Canine adipose-derived stem cells (CADSCs) include an xCT-positive subpopulation and show relatively low expression of osteogenic markers during in vitro osteogenic differentiation. Sulfasalazine (SSZ), a drug used to treat rheumatoid arthritis, suppresses xCT expression in cancer cells. In this study, we found that the SSZ treatment at 100 µM significantly suppressed xCT mRNA expression in CADSCs but did not significantly affect cell proliferation under the same conditions. Additionally, this treatment decreased the intracellular glutathione concentration. During in vitro osteogenic differentiation, the SSZ treatment at 50 µM and 100 µM significantly increased alizarin red staining and its quantification, as well as the concentration-dependent osteogenic differentiation markers (BMP1 and SPP) mRNA expression. Our results suggested that SSZ enhances the osteogenic differentiation potential of CADSCs and can potentially exhibit a superior therapeutic profile in canine bone regenerative medicine.
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- 2023
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20. Osteosarcoma of the hyoid bone in a cat.
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Nakaichi M, Itamoto T, Nemoto Y, Sunahara H, Itoh H, Itamoto K, and Tani K
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Case Summary: A 10-year-old male neutered Abyssinian cat was presented with the chief complaint of a right pharyngeal mass. On palpation, the mass was easily palpable; it appeared well demarcated and mobile, and oval in shape. Radiographic examination showed a radiopaque pharyngeal mass, which was revealed to be a well-demarcated mass lesion with a radiopaque marginal area on CT examination. The inside of the mass was uniformly well enhanced on contrast CT examination. A three-dimensional image reconstructed from the CT images strongly suggested that the mass originated from the right stylohyoid bone. No abnormal lesions were observed in the thoracic and abdominal CT examinations. Surgical excision of the mass was scheduled 3 weeks after the first admission. The mass was bluntly separated from the surrounding musculature and resected together with the ipsilateral epihyoid bone adjacent to the mass. Histopathological examination of the resected mass showed neoplastic cells with osteoid formation, and the mass was histopathologically diagnosed as an osteosarcoma. The postoperative recovery from anaesthesia was uneventful, and the cat began feeding on its own from the third postoperative day. The 3-month postoperative CT evaluation revealed no local recurrence or distant metastasis. The cat showed no abnormal findings at the time of writing (6 months postoperatively)., Relevance and Novel Information: Although osteosarcoma derived from the hyoid bone has rarely been reported in the veterinary field, this report suggests that such tumours may occur in cats. In addition, partial excision of the hyoid apparatus seems to be well tolerated in cats., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)
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- 2023
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21. Comparison of surgical invasiveness between micro-endoscopic discectomy/microscopic discectomy and conventional hemilaminectomy in dogs.
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Itamoto K, Itoh H, Sunahara H, Horikirizono H, Nemoto Y, Tani K, Iseri T, and Nakaichi M
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- Humans, Dogs, Animals, Diskectomy veterinary, Diskectomy methods, Endoscopy methods, Endoscopy veterinary, C-Reactive Protein, Microsurgery methods, Microsurgery veterinary, Lumbar Vertebrae, Treatment Outcome, Intervertebral Disc Displacement surgery, Intervertebral Disc Displacement veterinary, Dog Diseases surgery
- Abstract
Micro-endoscopic discectomy (MED) or microscopic discectomy (MD) have been performed for disc herniation in humans. The purpose of this study was to compare the invasiveness of the hemilaminectomy in dogs between the approach using a cylindrical retractor for the MED/MD and a conventional open surgical approaches in dogs. First, as preliminary studies, we analyzed the suitability of the cylindrical retractor for the vertebral body of small to medium-sized dogs on the X-ray computed tomographic images using the three-dimensional analysis software, and confirmed that it was possible to open a bone window of an approximate length of 1.72 clto the spinal canal with the cylindrical retractor with a diameter 17 mm using two medium-sized canine cadavers. Next, to determine difference in the invasiveness of hemilaminectomy, the magnitude of tissue damage, surgical stress and postoperative pain were compared between the conventional open approach (hemilaminectomy group: HL group, n=6) and the surgical approach using the cylindrical retractor (MD group, n=6) in 12 beagle dogs. The plasma creatine phosphokinase, C-reactive protein and cortisol concentrations, incision length and University of Melbourne Pain Scale scores after the hemilaminectomy were significantly lower in the MD group than in the HL group. There were no significant differences between the durations of surgery and the other evaluated indices. The approach using the MD can provide a less invasive hemilaminectomy than the conventional approach in dogs.
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- 2023
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22. Successful treatment with urgent revascularization and parent artery occlusion for a ruptured intratumoral aneurysm following prior meningioma surgery: illustrative case.
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Okuyama T, Kurisu K, Hokari M, Miyata K, Uchida K, Asaoka K, Itamoto K, and Fujimura M
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Background: An intratumoral aneurysm encased within the associated intracranial tumor is rare, and hemorrhage caused by its rupture is even more rare. While urgent and adequate surgical treatment is important, the treatment can be difficult given the limited understanding of this rare condition., Observations: A 69-year-old man who had undergone meningioma surgery 30 years prior presented with a disturbance in consciousness. Magnetic resonance imaging revealed massive intracerebral and subarachnoid hemorrhage. A round, partially calcified mass, which was diagnosed as recurrent meningioma, was also observed. Subsequent cerebral angiography revealed that the source of the hemorrhage was an intratumoral aneurysm in the dorsal internal carotid artery (ICA) encased within the recurrent meningioma. Urgent surgical ICA trapping and high-flow graft bypass were conducted. The postoperative course was uneventful, and he was referred to another hospital for rehabilitation., Lessons: This is the first case report of a ruptured intratumoral aneurysm being treated with urgent combined revascularization and parent artery trapping surgery. This surgical approach may be a feasible treatment option for such a challenging condition. Additionally, this case highlights the importance of diligent long-term follow-up after skull-base surgery, as minor intraoperative vascular wall injury may trigger the development and rupture of an intracerebral aneurysm.
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- 2023
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23. Histiocytic sarcoma with spinal necrosis in a dog with progressing non-ambulatory tetraparesis.
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Nemoto Y, Nakaichi M, Sakurai M, Itamoto K, Morimoto M, Horikirizono H, Itoh H, Sunahara H, and Tani K
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- Male, Dogs, Animals, Magnetic Resonance Imaging veterinary, Necrosis diagnosis, Necrosis veterinary, Thoracic Vertebrae, Histiocytic Sarcoma diagnosis, Histiocytic Sarcoma veterinary, Histiocytic Sarcoma pathology, Dog Diseases diagnosis, Dog Diseases pathology
- Abstract
Background: Histiocytic sarcoma (HS) is an aggressive malignant neoplasm, and widespread metastasis occurs with a fatal outcome. HS involving the central nervous system is relatively uncommon. Spinal cord necrosis, a very rare condition, could be induced by ischemia or infarction. Here, we report a dog progressing non-ambulatory tetraparesis with spinal cord necrosis caused by HS., Case Description: A 9-year-old male Labrador Retriever was presented with a progressing non-ambulatory tetraparesis. CT imaging revealed lysis of the spinous process of T7 and a ring-shaped lesion surrounding the soft tissue of lung fields. T2-weighted MRI showed the spinous processes of T6 to T8 as hyperintense, and the lesion infiltrated into the T7 vertebra and the spinal cord. After euthanasia, the final diagnosis upon necropsy was HS, which was observed in the lung, spinous process, thoracic cord, and the pulmonary hilar lymph node. Moreover, necrotic spots were spread widely through the thoracic spinal cord., Conclusion: This report outlines a case of canine HS in the lung, spinous process, thoracic cord, and pulmonary hilar lymph node. Ischemic deficit and necrosis of the thoracic spinal cord resulted from the compression of perivascular tumor cells, which rapidly led to progressive tetraparesis. Although the diagnosis was difficult, MRI and CT images helped determine the prognosis. To our knowledge, this is the first case report of canine HS with direct spinal cord involvement associated with spinal necrosis., Competing Interests: The authors declare that there is no conflict of interest.
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- 2023
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24. Evaluation of setup errors of immobilization device for radiation therapy in companion animals.
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Iseri T, Hira N, Tanabe Y, Horikirizono H, Sunahara H, Itoh H, Nemoto Y, Itamoto K, Tani K, and Nakaichi M
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- Animals, Cats, Dogs, Radiotherapy Planning, Computer-Assisted methods, Radiotherapy Planning, Computer-Assisted veterinary, Radiotherapy Dosage veterinary, Pets, Immobilization veterinary, Immobilization methods, Cat Diseases radiotherapy, Head and Neck Neoplasms veterinary, Dog Diseases
- Abstract
Background: Intensity-modulated radiotherapy (IMRT), which allows generating steep dose gradients, is a beneficial treatment for companion animals with adjacent target and risk organs. IMRT is essential for high setup accuracy for avoiding overdose to risk organs, and optimal radiotherapy is important for evaluating the setup accuracy of companion animals., Aim: To use an immobilization device to evaluate setup errors in radiotherapy for companion animals., Methods: We calculated setup errors in radiotherapy for 386 animals (dogs and cats; 3,261 registration images) that underwent radiotherapy between 2016 and 2022. The companion animals were immobilized with a customized bite block and vacuum lock device. A quantile-quantile plot with 95% confidence interval (CI) was used to evaluate the histogram of the setup errors, and the systematic and random setup errors were calculated for each region (brain, head and neck, chest and abdomen, pelvis, and spine)., Results: The setup error in each direction presented an extremely narrow-interval histogram, with the following lower and upper 95% CIs: cranial-caudal (-0.08, -0.06 cm); left-right (-0.04, -0.02 cm); and dorsal-ventral (-0.13, -0.11 cm). The mean systematic setup error was 0.16 cm (range: 0.12-0.36 cm), and the random error was 0.15 cm (range: 0.08-0.34 cm). The pelvis showed the highest systematic and random setup errors (mean: 0.36 and 0.23 cm, respectively)., Conclusion: The use of an immobilization device enables highly accurate radiotherapy for companion animals (95% CI < 0.15 cm)., Competing Interests: The authors declare that they have no conflict of interest.
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- 2022
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25. Intratumoral heterogeneity of c-KIT mutations in a feline splenic mast cell tumor and their functional effects on cell proliferation.
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Hasegawa Y, Shosu K, Tsuji K, Shimoyama Y, Miyama TS, Baba K, Okuda M, Itamoto K, Igase M, and Mizuno T
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- Amino Acids genetics, Animals, Cat Diseases genetics, Cats, Cell Proliferation genetics, DNA, Complementary, Interleukin-3 genetics, Mast Cells metabolism, Mice, Mutation, Nucleotides, Proto-Oncogene Proteins c-kit metabolism, Receptor Protein-Tyrosine Kinases genetics, Myeloproliferative Disorders genetics, Myeloproliferative Disorders veterinary, Spleen pathology
- Abstract
A cat was presented with mast cell tumors (MCTs) of the skin and spleen. During the initial diagnosis, the exon 8 mutation of c-KIT was detected in the masses from skin and spleen by a commercial laboratory test. Consequently, treatment with toceranib was started. After complete remission, because of recurrence on day 117, the spleen and skin tumors were removed, but the cat eventually died on day 191. The analysis of ten cDNA clones of the c-KIT gene cloned from the surgically removed spleen revealed that seven different cDNA patterns were included, indicating the heterogeneity of this gene in the splenic MCT. The seven cDNA nucleotide patterns can be classified into four protein sequence patterns. In addition to the previously known mutations in exon 8, we identified novel mutations in exons 9, 10, and 18; four amino acids deletion in exon 9, and a point mutation in exons 10 and 18. Mouse IL-3-dependent cell line, Ba/F3, was transduced with these mutant clones, and c-KIT phosphorylation and proliferation assays were performed. We found that certain mutations affected the c-KIT phosphorylation status and cell proliferation. This suggests that heterogeneity among the population of tumor cells exists in MCTs, and that the dominant clones of this heterogeneity may contribute to the subsequent tumor cell growth., (© 2022. The Author(s).)
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- 2022
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26. Relationship of microsatellite instability to mismatch repair deficiency in malignant tumors of dogs.
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Inanaga S, Igase M, Sakai Y, Hagimori K, Sunahara H, Horikirizono H, Itamoto K, Baba K, Ohsato Y, and Mizuno T
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- Animals, Brain Neoplasms, DNA, DNA Mismatch Repair genetics, Dogs, Formaldehyde, Microsatellite Instability, Neoplastic Syndromes, Hereditary, Colorectal Neoplasms genetics, Colorectal Neoplasms pathology, Colorectal Neoplasms veterinary, Dog Diseases genetics, Melanoma veterinary
- Abstract
Background: Microsatellite instability (MSI) is a type of genomic instability caused by mismatch repair deficiency (dMMR) in tumors. Studies on dMMR/MSI are limited, and the relationship between dMMR and MSI is unknown in tumors of dogs., Objectives: We aimed to identify the frequency of dMMR/MSI by tumor type and evaluate the relationship between dMMR and MSI in tumors of dogs., Animals: In total, 101 dogs with 11 types of malignant tumors were included., Methods: We extracted DNA from fresh normal and tumor tissues. Twelve microsatellite loci from both normal and tumor DNA were amplified by PCR and detected by capillary electrophoresis. Each microsatellite (MS) was defined as MSI if a difference in product size between the tumor and normal DNA was detected. The dMMR was evaluated by immunohistochemistry with formalin-fixed paraffin-embedded tumor tissues. Next, we confirmed whether dMMR induces MSI by serial passaging of MMR gene knockout cell lines for 3 months., Results: Microsatellite instability was detected frequently in oral malignant melanoma. The number of MSI-positive markers was higher in cases with dMMR than in those with proficient MMR (P < .0001). Statistical analysis indicated that the occurrence of MSI in FH2305 might have relevance to dMMR. Furthermore, MSI occurred in dMMR cell lines 3 months after passaging., Conclusions and Clinical Importance: Microsatellite instability and dMMR more frequently were found in oral malignant melanoma than in other tumors, and dMMR has relevance to MSI in both clinical cases and cell lines., (© 2022 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)
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- 2022
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27. Improvement of anemia in five dogs with nonregenerative anemia treated with allogeneic adipose-derived stem cells.
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Mizuno T, Inoue M, Kubo T, Iwaki Y, Kawamoto K, Itamoto K, Kambayashi S, Igase M, Baba K, and Okuda M
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Background: Nonregenerative anemia is occasionally seen in dogs and can be caused by many factors, among which nonregenerative immune-mediated anemia (NRIMA) and pure red cell anemia are relatively common causes. These are thought to be caused by immune-mediated destruction of the erythroid lineage and are treated with immunosuppressive drugs, but some of them are refractory or recurrent, so new treatments are needed., Objectives: To examine the efficacy of allogeneic adipose-derived stem cells (ADSCs) for the treatment of nonregerative anemia in dogs., Methods: ADSCs were administered to total five nonregenerative anemia cases; two NRIMA cases and two suspected NRIMA cases that were refractory to immunosuppressive agents, and one NRIMA case that has not been treated with immunosuppressive agents., Results: In all cases, anemia was improved, and blood transfusion was no longer necessary., Conclusions: This study suggests that allogeneic ADSCs may be one of the rescue therapies for the refractory immune-mediated anemia in dogs., Competing Interests: T.M. received research funding from FUJIFILM Corporation. KK was associated with Anicom Specialty Medical Institute Inc., Japan. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 The Author(s). Published by Elsevier Ltd.)
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- 2022
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28. Pedigree study of the heredity of copper-associated hepatitis in Dalmatians in Japan.
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Nakaichi M, Iseri T, Horikirizono H, Itoh H, Sunahara H, Nemoto Y, Itamoto K, and Tani K
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- Animals, Copper, Dogs, Japan epidemiology, Male, Pedigree, Dog Diseases chemically induced, Dog Diseases epidemiology, Dog Diseases genetics, Hepatitis genetics, Heredity
- Abstract
The pedigrees of 3 Dalmatian dogs afflicted with copper-associated hepatitis were investigated to discover the mode of inheritance. A composite family pedigree showed that the 3 affected Dalmatians were related. None of the parents of the affected dogs showed clinical symptoms of liver disease, and the disease had no sex predisposition. The estimated segregation ratio was approximately 3:1 based on surviving littermates. These findings suggested that the copper-associated hepatitis in these Dalmatians was an autosomal recessive mode of inheritance. In addition, some male Dalmatians imported from abroad might have been involved in the occurrence of this disease in Japan., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)
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- 2022
29. Establishment of a New Canine Inflammatory Mammary Carcinoma Cell Line and Analysis of its Cystine-glutamate Transporter Subunit Expression.
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Itoh H, Naruse R, Tani K, Sunahara H, Nemoto Y, Nakaichi M, Iseri T, Horikirizono H, and Itamoto K
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Introduction: Inflammatory mammary carcinoma (IMC) is a rare disease with a poor prognosis and one affecting dogs. Inflammatory breast carcinoma (IBC) is a subtype of malignant breast cancer in humans with a high degree of malignancy and a similarly poor prognosis. Since the clinical symptoms and prognoses of both are similar, canine IMC has been considered as a model of human IBC. In this study, we newly established a stable IMC-derived cell line from a patient at the Yamaguchi University Animal Medical Center in Japan., Material and Methods: The patient was a female toy poodle presenting with an inflamed mammary gland, which was diagnosed as IMC. The cell line was established from a tissue biopsy. Surface antigen marker (CD24 and CD44) expression was determined. Cystine/glutamate antiporter (xCT) expression was determined by Western blotting, flow cytometry and fluorescence immunostaining, and sulfasalazine was administered to ascertain if it suppressed xCT expression. Stem cell marker (Nanog, Sox2, Myc and Klf4) expression and aldehyde dehydrogenase (ALDH) activity were also investigated., Results: The cultured cells showed xCT, and its suppression showed downregulation of stem cell markers and ALDH activity. Stable cell proliferation was verified., Conclusion: A new canine IMC-derived cell line was established. In the future, we aim to study the effect of xCT on the maintenance of cancer stem cell properties in canine tumours, and propose a new therapeutic method for the treatment of canine IMC by targeting xCT., Competing Interests: Conflict of Interest Conflict of Interests Statement: The authors declare that there is no conflict of interests regarding the publication of this article., (© 2022 H. Itoh et al. published by Sciendo.)
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- 2022
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30. Outcomes of megavoltage radiotherapy for canine intranasal tumors and its relationship to clinical stages.
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Iseri T, Horikirizono H, Abe M, Itoh H, Sunahara H, Nemoto Y, Itamoto K, Tani K, and Nakaichi M
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- Animals, Dogs, Retrospective Studies, Dog Diseases pathology, Nose Neoplasms radiotherapy, Nose Neoplasms veterinary
- Abstract
Background: Radiation therapy is considered important for the treatment of intranasal tumors in dogs and is believed to be essential for prolonging their survival., Aim: To investigate the contribution of clinical staging to improve outcomes of megavoltage radiotherapy for canine intranasal tumors., Methods: A total of 123 dogs with intranasal tumors were included in the study. Forty-eight dogs received orthovoltage radiotherapy after cytoreductive surgery (Group I), 21 received orthovoltage radiotherapy without surgery (Group II), and 54 received megavoltage radiotherapy without surgery (Group III). All cases in each group were classified into clinical stages 1-4, and the median survival time (MST) was compared for each stage in all groups., Results: The overall MST was not significantly difference among Group I (325 days), Group II (317 days), and Group III (488 days); however, Group III was prolonged than Groups I and II. The MSTs for stages 1, 2, 3, and 4 were 597, 361, 267, and 325 days in Group I; 633, 260, 233, and 329 days in Group II; and 931, 860, 368, and 176 days in Group III, respectively. The MST for stage 2 cases in Group III was significantly prolonged when compared with that in Groups I and II; no significant difference was observed at other stages; however, the MST in Group III was longer in stage 1. These results showed that megavoltage radiotherapy prolonged the MST in dogs with intranasal tumors when compared to orthovoltage radiation with or without cytoreductive surgery, and that improvements in MST at stage 2 contributed significantly to this., Conclusion: The improvement in the MST in dogs with stages 1 and 2 intranasal tumors highlights the importance of starting megavoltage radiotherapy in the early stages.
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- 2022
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31. Adjustment of multi-leaf collimator parameters in 4-MV and 6-MV IMRT: A study of veterinary clinical cases.
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Iseri T, Tanabe Y, Horikirizono H, Sunahara H, Itoh H, Nemoto Y, Itamoto K, Tani K, Tanaka H, and Nakaichi M
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- Animals, Cats, Dogs, Radiotherapy Dosage veterinary, Radiotherapy Planning, Computer-Assisted veterinary, Cat Diseases, Dog Diseases radiotherapy, Radiotherapy, Intensity-Modulated veterinary
- Abstract
Background: For optimal treatment, it is important to maintain optimal multi-leaf collimator (MLC) transmission in intensity-modulated radiation therapy (IMRT). However, adjustment of transmissions has not been reported in veterinary medicine., Aim: To demonstrate that appropriate MLC parameter adjustment for IMRT using 4- and 6-MV energy can reduce the need for quality assurance revalidation in real companion animal clinical cases., Methods: The MLC parameters (leaf transmission and leaf offset) of the treatment planning system were adjusted by evaluating seven plans (10 × 10 cm, 3ABUT, DMLC, 7segA, FOURL, HDMLC, and HIMRT) and 20 preclinical cases (10 cases each in 4- and 6-MV groups). Subsequently, 101 IMRT plans of 88 cases (77 dogs and 11 cats) were evaluated for absolute dose of plan target volume (PTV) and organs at risk (OAR) and were analyzed for the relative dose distribution by gamma analysis (3%/3 mm, >10%) using EBT3 film., Results: After adjustment of the MLC parameters (leaf transmission and leaf offset, 4 MV: 0.008 and 0, 6 MV: 0.005 and 0, respectively), the data from 101 plans (4 MV: 64 plans and 6 MV: 37 plans) treated with IMRT showed PTV <3%, OAR <5%, and gamma analysis pass rates ≥95% in all cases., Conclusion: Clinically meaningful dose distributions can be created even with a limited validation device if the treatment parameters are adjusted appropriately, even for tumors in canines and felines, where the irradiation field is small, the target is adjacent to the OAR, and the target is often superficial.
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- 2022
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32. A long survival case of spinal nephroblastoma in a dog.
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Nakaichi M, Iseri T, Horikirizono H, Itoh H, Sunahara H, Nemoto Y, Itamoto K, and Tani K
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- Animals, Dogs, Female, Laminectomy veterinary, Dog Diseases diagnosis, Dog Diseases pathology, Dog Diseases surgery, Kidney Neoplasms surgery, Kidney Neoplasms veterinary, Spinal Cord Neoplasms diagnosis, Spinal Cord Neoplasms surgery, Spinal Cord Neoplasms veterinary, Wilms Tumor diagnosis, Wilms Tumor surgery, Wilms Tumor veterinary
- Abstract
Background: Dogs' nephroblastoma of the spinal cord is a rare neoplastic disease, with few reports of long-term survival after surgery. We experienced that surgical treatment with postoperative radiation therapy for spinal nephroblastoma in a dog resulted in the long-term survival of 11 years., Case Description: The patient presented to our veterinary hospital because of progressive hindlimb paralysis. Based on diagnostic imaging, she was diagnosed with a thoracolumbar spinal cord tumor and was treated with surgery. The gross tumor tissue was removed after laminectomy, followed by postoperative radiation therapy using orthovoltage equipment. The histopathological features of the surgical specimen were consistent with those of previously reported spinal nephroblastoma, although infrequent mitotic figures were observed. The dog recovered well after treatment and resumed her normal walking condition. No tumor recurrence was observed on periodic follow-up magnetic resonance imaging performed 10 and 21 months after surgery. Imaging evaluation for the gradual development of hindlimb weakness was performed 9 years after surgery; however, no recurrence of tumor tissue was observed, and spondylosis deformans, probably induced after laminectomy, were identified as a possible cause. The dog died of aspiration pneumonia 11 years after surgery, independent of spinal nephroblastoma., Conclusion: To date, no clinical cases of canine spinal cord primary nephroblastoma that survived for 11 years after surgery have been reported. This case strongly suggests that providing intensive treatment for canine spinal nephroblastoma is very important., Competing Interests: None of the authors of this article has a financial or personal relationship with other people or organizations that could inappropriately influence or bias the content of this paper.
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- 2022
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33. Effect of drug-eluting bead transarterial chemoembolization loaded with cisplatin on normal dogs.
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Nakasumi K, Yamamoto N, Takami T, Itoh H, Itamoto K, Horikirizono H, Iseri T, Nakaichi M, Nemoto Y, Sunahara H, and Tani K
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- Animals, Cisplatin, Dogs, Doxorubicin, Hepatic Artery, Treatment Outcome, Carcinoma, Hepatocellular veterinary, Chemoembolization, Therapeutic veterinary, Dog Diseases drug therapy, Liver Neoplasms veterinary, Pharmaceutical Preparations
- Abstract
Transcatheter arterial embolization (TAE) and transcatheter arterial chemoembolization (TACE) are standard treatments for advanced hepatocellular carcinoma (HCC) and particularly for unresectable tumors or liver metastases in humans. However, reports on TACE used in veterinary medicine are few. This study aimed to evaluate the feasibility and safety of drug-eluting bead transarterial chemoembolization (DEB-TACE). We performed DEB-TACE in four clinically normal dogs and pharmacokinetically compared the results against hepatic arterial infusion (HAI) of cisplatin in two dogs. Drug-eluting beads (DEB) loaded with cisplatin were injected through a microcatheter for selective embolization of the left hepatic artery. After embolization, computed tomography (CT) images and histological examination findings were obtained during a 4-week observation period. Serum platinum concentrations were measured to evaluate cisplatin after each procedure. Biochemical analysis was performed during a 12-week observation period. Embolization was successful in all dogs, and there were no clinically apparent abnormalities. Embolization was confirmed up to 4 weeks after DEB-TACE in two of the four dogs and up to 1 week in the other two dogs using postoperative CT images. Cisplatin was not detected in peripheral veins in all dogs after DEB-TACE, but it was detected in trace amounts after HAI. DEB-TACE using cisplatin was safe and well tolerated by normal dogs. DEB-TACE may be useful in terms of determining systemic toxicity and drug concentration within tumors.
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- 2022
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34. Mismatch repair deficiency in canine neoplasms.
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Inanaga S, Igase M, Sakai Y, Tanabe M, Shimonohara N, Itamoto K, Nakaichi M, and Mizuno T
- Subjects
- Animals, Brain Neoplasms, DNA-Binding Proteins, Dogs, Mismatch Repair Endonuclease PMS2, MutL Protein Homolog 1 genetics, MutS Homolog 2 Protein genetics, Neoplastic Syndromes, Hereditary, Carcinoma, Transitional Cell veterinary, Colorectal Neoplasms veterinary, Dog Diseases, Urinary Bladder Neoplasms veterinary
- Abstract
The DNA mismatch repair (MMR) system preserves genomic stability by identifying and repairing mismatched nucleotides in the DNA replication process. The dysfunction of the MMR system, also known as mismatch repair deficiency (dMMR), is implicated as a predictive biomarker for the efficacy of immune checkpoint blockade therapy regardless of the tumor type in humans. This study aimed to evaluate the immunolabeling of MMR proteins in canine tumors and to identify the types of tumors having dMMR. First, we performed immunohistochemistry in 8 different canine tumors (oral malignant melanoma, high-to-intermediate grade lymphoma, mast cell tumor, malignant mammary gland tumor, urothelial carcinoma, hepatocellular carcinoma, osteosarcoma, and hemangiosarcoma) with 15 samples each to analyze the immunolabeling of canine mismatch repair proteins (MSH2, MSH6, and MLH1) using anti-human monoclonal antibodies. We found that more than half of canine oral malignant melanoma (60%) and hepatocellular carcinoma (53%) samples and fewer of the other canine tumors had loss of immunolabeling in ≥1 MMR protein (ie, evidence of defective MMR proteins, based on the definition of dMMR in the humans). Antibodies against human MSH2, MSH6, and MLH1 were cross-reactive with the corresponding canine protein as confirmed using MMR gene knockout canine cell lines. Further studies are required to investigate the clinical outcomes in canine spontaneous tumors with dMMR to determine the potential for immune checkpoint blockade therapy for these tumor types.
- Published
- 2021
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35. Transient third-degree atrioventricular block during anesthesia in a cat.
- Author
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Sunahara H, Tani K, Nemoto Y, Itamoto K, Itoh H, Nakaichi M, Iseri T, and Horikirizono H
- Subjects
- Animals, Cats, Heart Rate, Male, Anesthesia veterinary, Atrioventricular Block diagnosis, Atrioventricular Block etiology, Atrioventricular Block veterinary, Cat Diseases chemically induced, Cat Diseases diagnosis
- Abstract
Background: Third-degree atrioventricular block (AVB) is usually permanent, with transient cases being rare. Cats with transient third-degree AVB. It had been not reported in detail., Case Description: A 9.3-year-old, male shorthair cat was evaluated for possible nervous disease resulting from otitis interna. Under propofol and isoflurane anesthesia, this cat developed a third-degree AVB. Isoproterenol was administered by continuous infusion to increase its heart rate. During recovery, heart rate returned to sinus bradycardia together with first-degree AVB without medical treatment. The cause of transient AVB was not observed at the examination., Conclusion: The case of this cat suggests that anesthesia can result in a transient third-degree AVB., Competing Interests: The authors declare no potential conflicts of interest with respect to the research, authorship, and publication of this article.
- Published
- 2021
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36. The impact of pancreas compression time during minimally invasive gastrectomy on the postoperative complications in gastric cancer.
- Author
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Itamoto K, Hikage M, Fujiya K, Kamiya S, Tanizawa Y, Bando E, and Terashima M
- Abstract
Aim: Pancreas compression during minimally invasive gastrectomy causes blunt injury to the pancreas and leads to postoperative complications. However, the extent of practical compression associated with the incidence of postoperative complications remains unknown. This study aimed to evaluate the impact of pancreas compression, particularly the duration of compression, on short-term outcomes in minimally invasive gastrectomy for gastric cancer., Methods: This study included 178 patients who underwent laparoscopic or robotic gastrectomy at the Shizuoka Cancer Center in 2018. The total time of pancreas compression during gastrectomy was measured using video-reviews, and the correlation between the time and surgical outcomes was evaluated., Results: A duration of 3 min was selected as the cutoff value of pancreas compression time to predict high drain amylase concentration on postoperative day 1 (≥1000 U/L). The incidence of clinically relevant pancreatic fistula (1.5% vs 12.4%, P = .011) and all postoperative complications (12.3% vs 30.1%, P = .010) were significantly higher in the longer-compression group than in the shorter-compression group. The multivariable analysis identified longer compression as the only independent risk factor for postoperative complications., Conclusion: More than a few minutes of pancreas compression during minimally invasive gastrectomy was associated with a higher incidence of postoperative complications., Competing Interests: Funding: The authors declare that no external funding was received for this study. Conflict of Interest: The authors declare no Conflicts of Interest for this article. Author contributions: The authors meet all the criteria of the International Committee of Medical Journal Editors (ICMJE). Ethical statement: The protocol for this research project was approved by a suitably constituted Ethics Committee of the institution and it conforms to the provisions of the Declaration of Helsinki. Institutional Review Board of the Shizuoka Cancer Center, Approval No. J2019‐173. Informed consent was substituted by the informed opt‐out procedure because of the retrospective nature of the study, and anonymous clinical data were used for the analysis., (© 2021 The Authors. Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterology.)
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- 2021
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37. Copper-associated hepatitis in a young Dalmatian dog in Japan.
- Author
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Nakaichi M, Iseri T, Horikirizono H, Komine M, Itoh H, Sunahara H, Nemoto Y, Itamoto K, and Tani K
- Subjects
- Animals, Copper, Dogs, Japan, Liver, Male, Dog Diseases, Hepatitis, Chronic veterinary, Liver Diseases veterinary
- Abstract
A male 25-month-old Dalmatian dog attended our veterinary hospital because of anorexia and high circulating liver enzyme activities. Abdominal computed tomography showed a slightly small liver with rounded edges, and laparoscopic examination showed that the liver was yellowish. Histopathological examination revealed multifocal necrosis of hepatocytes and severe chronic hepatitis. Rhodanine staining showed severe copper accumulation in hepatocytes and a quantitative analysis of the copper content of the liver showed substantial accumulation (10.3 mg/g dry mass), suggesting a diagnosis of copper-associated hepatitis. Previously reported canine mutation in the COMMD1, the gene responsible for the copper-associated hepatitis in the Bedlington terrier, was not identified. To our knowledge, this is the first report of copper-associated hepatitis in a Dalmatian in Japan.
- Published
- 2021
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38. Clinical features and their course of pituitary carcinoma with distant metastasis in a dog.
- Author
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Nakaichi M, Iseri T, Horikirizono H, Sakai Y, Itoh H, Sunahara H, Itamoto K, and Tani K
- Subjects
- Adrenocorticotropic Hormone, Animals, Dogs, Male, Splenectomy veterinary, Tomography, X-Ray Computed, Dog Diseases, Pituitary Neoplasms veterinary
- Abstract
An 11-year-old male toy poodle with neurological symptoms was diagnosed with a macroscopic pituitary tumor, which produced adrenocorticotropic hormone. Radiation therapy with a linear accelerator was performed for the pituitary tumor, and resulted in good local tumor control. However, serum endogenous adrenocorticotropic hormone concentrations were uncontrollable even after the tumor disappeared. Abdominal computed tomography revealed splenic masses, and splenectomy was performed. Histopathological examination of the surgical specimen showed tumor cells with eosinophilic and finely granular cytoplasm suggestive of endocrine origin. Since these cells were positive for adrenocorticotropic hormone, the case was diagnosed as a pituitary carcinoma with distant metastasis. Necropsy revealed multiple metastases to the abdominal organs. This is the first case report describing canine pituitary carcinoma with distant metastasis.
- Published
- 2020
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39. Use of an inertial measurement unit sensor in pedicle screw placement improves trajectory accuracy.
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Baba S, Kawaguchi K, Itamoto K, Watanabe T, Hayashida M, Mae T, Nakashima Y, and Kato G
- Subjects
- Animals, Cadaver, Female, Lumbar Vertebrae surgery, Models, Theoretical, Pedicle Screws trends, Surgical Instruments, Swine, Thoracic Vertebrae surgery, Tomography, X-Ray Computed, Dimensional Measurement Accuracy, Microsurgery methods, Spinal Fusion methods
- Abstract
Ascertaining the accuracy of the pedicle screw (PS) trajectories is important as PS malpositioning can cause critical complications. We aimed to determine the angle range over which estimation is unreliable; build a low-cost PS placement support system that uses an inertial measurement unit (IMU) to enable the monitoring of surgical tools and PS trajectories, and determine the situations where IMU support would be most beneficial. In PS insertion experiments, we used cadaver samples that included lumbar porcine spines. Computed tomography images obtained before and after PS insertion were viewed. Offsets between the planned and implanted PS trajectories in the freehand and IMU-assisted groups were analyzed. The PS cortical bone breaches were classified according to the Gertzbein and Robbins criteria (GRC). Added head-down tilted sample experiments were repeated wherein we expected a decreased rostro-caudal rotational accuracy of the PS according to the angle estimation ability results. Evaluation of the PS trajectory accuracy revealed no significant advantage of IMU-assisted rostro-caudal rotational accuracy versus freehand accuracy. According to the GRC, IMU assistance significantly increased the rate of clinically acceptable PS positions (RoCA) than the freehand technique. In the head-down tilted sample experiments, IMU assist provided increased accuracies with both rostro-caudal and medial rotational techniques when compared with the freehand technique. In the freehand group, RoCA was significantly decreased in samples with rostral tilting relative to that in the samples without. However, In the IMU-assisted group, no significant difference in RoCA between the samples with and without head-down tilting was observed. Even when the planned PS medial and/or rostro-caudal rotational angle was relatively large and difficult to reproduce manually, IMU-support helped maintain the PS trajectory accuracy and positioning safety. IMU assist in PS placement was more beneficial, especially for larger rostro-caudal and/or medial rotational pedicle angles., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2020
- Full Text
- View/download PDF
40. A pilot clinical study of the therapeutic antibody against canine PD-1 for advanced spontaneous cancers in dogs.
- Author
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Igase M, Nemoto Y, Itamoto K, Tani K, Nakaichi M, Sakurai M, Sakai Y, Noguchi S, Kato M, Tsukui T, and Mizuno T
- Subjects
- Animals, Antineoplastic Agents, Immunological immunology, Antineoplastic Agents, Immunological therapeutic use, Autoantibodies immunology, Dogs, Female, Immunotherapy methods, Male, Melanoma immunology, Melanoma therapy, Melanoma veterinary, Mouth Neoplasms immunology, Mouth Neoplasms therapy, Mouth Neoplasms veterinary, Neoplasms immunology, Neoplasms therapy, Pilot Projects, Autoantibodies therapeutic use, Dog Diseases therapy, Immunotherapy veterinary, Neoplasms veterinary, Programmed Cell Death 1 Receptor immunology
- Abstract
Inhibition of programmed death 1 (PD-1), expressed on activated T cells, can break through immune resistance and elicit durable responses in human melanoma as well as other types of cancers. Canine oral malignant melanoma is one of the most aggressive tumors bearing poor prognosis due to its high metastatic potency. However, there are few effective treatments for the advanced stages of melanoma in veterinary medicine. Only one previous study indicated the potential of the immune checkpoint inhibitor, anti-canine PD-L1 therapeutic antibody in dogs, and no anti-canine PD-1 therapeutic antibodies are currently available. Here, we developed two therapeutic antibodies, rat-dog chimeric and caninized anti-canine PD-1 monoclonal antibodies and evaluated in vitro functionality for these antibodies. Moreover, we conducted a pilot study to determine their safety profiles and clinical efficacy in spontaneously occurring canine cancers. In conclusion, the anti-canine PD-1 monoclonal antibody was relatively safe and effective in dogs with advanced oral malignant melanoma and other cancers. Thus, our study suggests that PD-1 blockade may be an attractive treatment option in canine cancers.
- Published
- 2020
- Full Text
- View/download PDF
41. Cystine transporter expression is a marker to identify a subpopulation of canine adipose-derived stem cells.
- Author
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Itoh H, Nishikawa S, Tani K, Sunahara H, Nakaichi M, Iseri T, Taura Y, and Itamoto K
- Subjects
- Adipogenesis, Animals, Cell Proliferation, Cell Separation, Kruppel-Like Factor 4, Osteogenesis, Adipose Tissue cytology, Antigens, Differentiation metabolism, Cystine metabolism, Dogs anatomy & histology, Mesenchymal Stem Cells metabolism
- Abstract
Adipose-derived stem cells (ADSCs) are promising cell sources for regenerative medicine due to the simplicity of their harvest and culture; however, their biological properties are not completely understood. Moreover, recent murine and human studies identified several functional subpopulations of ADSCs varying in differentiation potential; however, there is a lack of research on canine ADSCs. Cystine transporter (xCT) is a stem cell marker in gastric and colon cancers that interacts with CD44 to enhance cystine uptake from the cell surface and subsequently accelerates intercellular glutathione levels. In this study, we identified a ~5% functional subpopulation of canine ADSCs with xCT
+ expression (xCTHi ). Compared with those of the xCT- subpopulation (xCTLo ), the xCTHi subpopulation showed a significantly higher proliferation rate, higher expression of conventional stem cell markers (SOX2, KLF4, and c-Myc), and higher expression of adipogenic markers (FABP4 and PPARγ). By contrast, the xCTLo subpopulation showed significantly higher expression of osteogenic markers (BMP1 and SPP) than xCTHi cells. These results suggest xCT as a candidate marker for detecting a functional subpopulation of canine ADSCs. Mechanistically, xCT could increase the adipogenic potential while decreasing the osteogenic differentiation potential, which could serve as a valuable target marker in regenerative veterinary medicine.- Published
- 2020
- Full Text
- View/download PDF
42. Agenesis of hepatic lobes in a dog.
- Author
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Oishi Y, Tani K, Itamoto K, Haraguchi T, and Taura Y
- Abstract
Agenesis of a hepatic lobe is an extremely rare congenital anomaly and only one dog have been reported in veterinary literature. We encountered a dog with this anomaly diagnosed by Computed tomography (CT) and portography. A two-year-old, 6.9-kg female Shih tzu dog was presented with vomiting and anorexia. The dog had no history of abdominal surgery or trauma. Biochemical analysis showed elevated plasmatic liver enzymes. CT revealed the absence of the liver parenchyma and vascular system of the left lobe, quadrate lobe and papillary process of the caudate lobe. A portosystemic shunt was also observed. The liver parenchyma and vascular system of these lobes were not detected under digital subtraction angiography during laparotomy. Furthermore, the liver parenchyma and vascular system of these lobes were not detected even when the remaining liver volume increased two months after treating the shunt vessel. CT proved itself a good option for antemortally diagnosis of hepatic agenesis in a dog.
- Published
- 2018
- Full Text
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43. Establishment of a dog primary prostate cancer organoid using the urine cancer stem cells.
- Author
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Usui T, Sakurai M, Nishikawa S, Umata K, Nemoto Y, Haraguchi T, Itamoto K, Mizuno T, Noguchi S, Mori T, Iwai S, Nakagawa T, Yamawaki H, Ohama T, and Sato K
- Subjects
- Animals, Dogs, Heterografts, Male, Mice, Mice, Inbred NOD, Mice, SCID, Cell Culture Techniques methods, Disease Models, Animal, Neoplastic Stem Cells pathology, Organoids, Prostatic Neoplasms, Urine cytology
- Abstract
Dog spontaneously develop prostate cancer (PC) like humans. Because most dogs with PC have a poor prognosis, they could be used as a translational model for advanced PC in humans. Stem cell-derived 3-D organoid culture could recapitulate organ structures and physiology. Using patient tissues, a human PC organoid culture system was established. Recent study has shown that urine cells also possess the characteristic of stem cells. However, urine cell-derived PC organoids have never been produced. Therefore, we generated PC organoids using the dog urine samples. Urine organoids were successfully generated from each dog with PC. Each organoid showed cystic structures and resembled the epithelial structures of original tissues. Expression of an epithelial cell marker, E-cadherin, and a myofibloblast marker, α-SMA, was observed in the urine organoids. The organoids also expressed a basal cell marker, CK5, and a luminal cell marker, CK8. CD49f-sorted basal cell organoids rapidly grew compared with CD24-sorted luminal cell organoids. The population of CD44-positive cells was the highest in both organoids and the original urine cells. Tumors were successfully formed with the injection of the organoids into immunodeficient mice. Treatment with a microtubule inhibitor, docetaxel, but not a cyclooxygenase inhibitor, piroxicam, and an mTOR inhibitor, rapamycin, decreased the cell viability of organoids. Treatment with a Hedgehog signal inhibitor, GANT61, increased the radiosensitivity in the organoids. These findings revealed that PC organoids using urine might become a useful tool for investigating the mechanisms of the pathogenesis and treatment of PC in dogs., (© 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)
- Published
- 2017
- Full Text
- View/download PDF
44. Aldehyde dehydrogenase activity helps identify a subpopulation of murine adipose-derived stem cells with enhanced adipogenic and osteogenic differentiation potential.
- Author
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Itoh H, Nishikawa S, Haraguchi T, Arikawa Y, Eto S, Hiyama M, Iseri T, Itoh Y, Nakaichi M, Sakai Y, Tani K, Taura Y, and Itamoto K
- Abstract
Aim: To identify and characterize functionally distinct subpopulation of adipose-derived stem cells (ADSCs)., Methods: ADSCs cultured from mouse subcutaneous adipose tissue were sorted fluorescence-activated cell sorter based on aldehyde dehydrogenase (ALDH) activity, a widely used stem cell marker. Differentiation potentials were analyzed by utilizing immunocytofluorescece and its quantitative analysis., Results: Approximately 15% of bulk ADSCs showed high ALDH activity in flow cytometric analysis. Although significant difference was not seen in proliferation capacity, the adipogenic and osteogenic differentiation capacity was higher in ALDH
Hi subpopulations than in ALDHLo . Gene set enrichment analysis revealed that ribosome-related gene sets were enriched in the ALDHHi subpopulation., Conclusion: High ALDH activity is a useful marker for identifying functionally different subpopulations in murine ADSCs. Additionally, we suggested the importance of ribosome for differentiation of ADSCs by gene set enrichment analysis., Competing Interests: Conflict-of-interest statement: Authors have no conflicts of interest.- Published
- 2017
- Full Text
- View/download PDF
45. Aldehyde dehydrogenase activity identifies a subpopulation of canine adipose-derived stem cells with higher differentiation potential.
- Author
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Itoh H, Nishikawa S, Haraguchi T, Arikawa Y, Hiyama M, Eto S, Iseri T, Itoh Y, Tani K, Nakaichi M, Taura Y, and Itamoto K
- Subjects
- Adipose Tissue enzymology, Animals, Cells, Cultured, Dogs, Female, Male, Stem Cells cytology, Adipogenesis, Adipose Tissue cytology, Aldehyde Dehydrogenase metabolism, Osteogenesis, Stem Cells enzymology
- Abstract
Adipose-derived stem cells (ADSCs) are abundant and readily obtained, and have been studied for their clinical applicability in regenerative medicine. Some surface antigens have been identified as markers of different ADSC subpopulations in mice and humans. However, it is unclear whether functionally distinct subpopulations exist in dogs. To address this issue, we evaluated aldehyde dehydrogenase (ALDH) activity-a widely used stem cell marker in mice and humans-by flow cytometry. Approximately 20% of bulk ADSCs showed high ALDH activity. Compared to cells with low activity (ALDH
Lo ), the high-activity (ALDHHi ) subpopulation exhibited a higher capacity for adipogenic and osteogenic differentiation. This is the first report of distinct ADSC subpopulations in dogs that differ in terms of adipogenic and osteogenic differentiation potential.- Published
- 2017
- Full Text
- View/download PDF
46. Comparison of postoperative pain and inflammation reaction in dogs undergoing preventive laparoscopic-assisted and incisional gastropexy.
- Author
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Haraguchi T, Kimura S, Itoh H, Nishikawa S, Hiyama M, Tani K, Iseri T, Itoh Y, Nakaichi M, Taura Y, and Itamoto K
- Subjects
- Animals, C-Reactive Protein metabolism, Dogs, Female, Gastric Dilatation prevention & control, Gastropexy adverse effects, Hydrocortisone blood, Inflammation etiology, Inflammation veterinary, Interleukin-6 blood, Laparoscopy adverse effects, Male, Pain, Postoperative etiology, Stomach Volvulus prevention & control, Gastric Dilatation veterinary, Gastropexy veterinary, Laparoscopy veterinary, Pain, Postoperative veterinary, Stomach Volvulus veterinary
- Abstract
This study compared the effects of postoperative pain and inflammation reaction after preventive laparoscopic-assisted gastropexy (LAG) and incisional gastropexy (IG) in 10 clinically normal Beagles. Surgical time, incision length, visual analog scale (VAS) score, University of Melbourne Pain Scale (UMPS) score, and plasma C-reactive protein (CRP), plasma cortisol (COR), and serum interleukin-6 (IL-6) levels were evaluated. The VAS and UMPS scores and COR and IL-6 levels were recorded at 0.5, 1, 2, 4, 8, 12, 18 and 24 hr after surgery. CRP level was recorded at 12, 24 and 48 hr after surgery. The VAS and UMPS scores showed no significant intergroup differences. Compared to IG, LAG had significantly lower surgical time (45 ± 9.91 min vs 64 ± 5.30 min; P<0.05), incision length (46 ± 8.21 mm vs 129 ± 19.49 mm; P<0.05), CRP level (12 hr after surgery; 4.58 ± 1.58 mg/dl vs 12.4 ± 1.34 mg/dl; P<0.01), and COR level (1 hr after surgery; 10.79 ± 3.07 µg/dl vs 15.9 ± 3.77 µg/dl; P<0.05). IL-6 levels showed no significant intergroup differences at any time point. However, LAG resulted in lower IL-6 levels than did IG at all postoperative time points. Neither procedure resulted in significant surgical complications. LAG produced lower surgical stress than did IG, suggesting that LAG is a safe, minimally invasive, and highly useful technique for preventing canine gastric dilatation-volvulus. Nevertheless, since this study used experimental models, its usefulness should be evaluated in future cases.
- Published
- 2017
- Full Text
- View/download PDF
47. Identification of rhodamine 123-positive stem cell subpopulations in canine hepatocellular carcinoma cells.
- Author
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Itoh H, Nishikawa S, Haraguchi T, Arikawa Y, Hiyama M, Iseri T, Itoh Y, Nakaichi M, Taura Y, Tani K, and Itamoto K
- Abstract
The majority of cases of chemotherapy for hepatocellular carcinoma (HCC) are not effective in human or veterinary medicine due to resistance against anticancer agents. In human medicine, hepatocellular carcinoma stem cells (HCSCs) were recently identified as cytokeratin 19 (CK19)-, cluster of differentiation (CD)-44-, and CD133-positive. However, there are few previous reports regarding canine HCSC (cHCSC). Additionally, to the best of our knowledge, the chemoresistance against anticancer agents of these cHCSCs has not been investigated. In the present study staining of cHCSCs was performed with rhodamine 123, a low-toxicity fluorescent dye for mitochondria, by flow cytometry. There were two subpopulations in the HCC cell line defined by their higher (Rho
Hi ) and lower (RhoLo ) fluorescence intensity of rhodamine 123. The RhoHi subpopulation demonstrated a higher Nanog gene expression, sphere-forming ability, and chemoresistance against gemcitabine. However, there was no significant difference between RhoHi and RhoLo regarding the proliferation rate and chemoresistance against mitoxantrone and doxorubicin. The present results indicate that the expression of rhodamine 123 identifies different stem cell subpopulations in a canine HCC cell line.- Published
- 2017
- Full Text
- View/download PDF
48. Craniocervical junction abnormalities with atlantoaxial subluxation caused by ventral subluxation of C2 in a dog.
- Author
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Itoh H, Itamoto K, Eto S, Haraguchi T, Nishikawa S, Tani K, Itoh Y, Hiyama M, Iseri T, Nakaichi M, and Taura Y
- Abstract
Craniocervical junction abnormalities with atlantoaxial subluxation caused by ventral subluxation of C2 were diagnosed in a 6-month-old female Pomeranian with tetraplegia as a clinical sign. Lateral survey radiography of the neck with flexion revealed atlantoaxial subluxation with ventral subluxation of C2. Computed tomography revealed absence of dens and atlanto-occipital overlapping. Magnetic resonance imaging showed compression of the spinal cord and indentation of caudal cerebellum. The diagnosis was Chiari-like malformation, atlantoaxial subluxation with ventral displacement of C2, atlanto-occipital overlapping, and syringomyelia. The dog underwent foramen magnum decompression, dorsal laminectomy of C1, and ventral fixation of the atlantoaxial joint. Soon after the operation, voluntary movements of the legs were recovered. Finally, the dog could stand and walk without assistance. The dog had complicated malformations at the craniocervical junction but foramen magnum decompression and dorsal laminectomy for Chiari-like malformation, and ventral fixation for atlantoaxial subluxation resulted in an excellent clinical outcome.
- Published
- 2017
- Full Text
- View/download PDF
49. Single-Cell Phosphospecific Flow Cytometric Analysis of Canine and Murine Adipose-Derived Stem Cells.
- Author
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Itoh H, Nishikawa S, Haraguchi T, Arikawa Y, Hiyama M, Iseri T, Itoh Y, Nakaichi M, Taura Y, Tani K, and Itamoto K
- Abstract
This study aimed to demonstrate single-cell phosphospecific flow cytometric analysis of canine and murine adipose-derived stem/stromal cells (ADSCs). ADSCs were obtained from clinically healthy laboratory beagles and C57BL/6 mice. Cell differentiation into adipocytes, osteocytes, and chondrocytes was observed for the cultured canine ADSCs (cADSCs) and murine ADSCs (mADSCs) to determine their multipotency. We also performed single-cell phosphospecific flow cytometric analysis related to cell differentiation and stemness. Cultured cADSCs and mADSCs exhibited the potential to differentiate into adipocytes, osteocytes, and chondrocytes. In addition, single-cell phosphospecific flow cytometric analysis revealed similar β -catenin and Akt phosphorylation between mADSCs and cADSCs. On the other hand, it showed the phosphorylation of different Stat proteins. It was determined that cADSCs and mADSCs show the potential to differentiate into adipocytes, osteocytes, and chondrocytes. Furthermore, a difference in protein phosphorylation between undifferentiated cADSCs and mADSCs was identified.
- Published
- 2017
- Full Text
- View/download PDF
50. Development of hepatocellular carcinoma after long-term immunosuppressive therapy including danazol in a dog.
- Author
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Kobayashi K, Shimokawa Miyama T, Itamoto K, Noguchi S, Baba K, Mizuno T, and Okuda M
- Subjects
- Anemia drug therapy, Anemia immunology, Anemia veterinary, Animals, Carcinoma, Hepatocellular chemically induced, Carcinoma, Hepatocellular diagnostic imaging, Dog Diseases diagnostic imaging, Dogs, Female, Liver Neoplasms chemically induced, Tomography, X-Ray Computed veterinary, Carcinoma, Hepatocellular veterinary, Danazol adverse effects, Dog Diseases chemically induced, Immunosuppressive Agents adverse effects, Liver Neoplasms veterinary
- Abstract
A 2-year-old female beagle was referred to our hospital for evaluation of anemia. Laboratory tests, including bone marrow cytology, revealed non-regenerative immune-mediated anemia (NRIMA). Although initial immunosuppressive multi-drug therapy was not effective, additional administration of danazol was successful in treating the anemia. However, hepatocellular carcinoma (HCC) developed about 20 months after the administration of danazol. In humans, several cases of development of HCC after the administration of danazol have been reported. The present report describes a case of HCC development in a dog after chronic administration of danazol in addition to other immunosuppressive drugs.
- Published
- 2016
- Full Text
- View/download PDF
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