Search

Your search keyword '"G Hankey"' showing total 29 results
Start Over Author "G Hankey" Topic medicine.disease
29 results on '"G Hankey"'

1. The Natural History of Acute Radiation-induced H-ARS and Concomitant Multi-Organ Injury in the Nonhuman Primate: The MCART experience

Author

Catherine Booth, Kim G. Hankey, Thomas J. MacVittie, Greg L. Tudor, Wanchang Cui, George A. Parker, Eric P. Cohen, and Ann M. Farese

Subjects
medicine.medical_specialty, Epidemiology, business.industry, Health, Toxicology and Mutagenesis, Acute kidney injury, Urology, Acute Radiation Syndrome, Context (language use), Dose-Response Relationship, Radiation, Total body irradiation, medicine.disease, Macaca mulatta, Pathophysiology, Article, Haematopoiesis, medicine.anatomical_structure, Bone Marrow, Concomitant, medicine, Animals, Radiology, Nuclear Medicine and imaging, Bone marrow, business, Whole-Body Irradiation
Abstract

The dose response relationship and corresponding values for mid-lethal dose and slope are used to define the dose- and time-dependent parameters of the hematopoietic acute radiation syndrome. The characteristic time course of mortality, morbidity, and secondary endpoints are well defined. The concomitant comorbidities, potential mortality, and other multi-organ injuries that are similarly dose- and time-dependent are less defined. Determination of the natural history or pathophysiology associated with the lethal hematopoietic acute radiation syndrome is a significant gap in knowledge, especially when considered in the context of a nuclear weapon scenario. In this regard, the exposure is likely ill-defined, heterogenous, and nonuniform. These conditions forecast sparing of bone marrow and increased survival from the acute radiation syndrome consequent to threshold doses for the delayed effects of acute radiation exposure due to marrow sparing, medical management, and use of approved medical countermeasures. The intent herein is to provide a composite natural history of the pathophysiology concomitant with the evolution of the potentially lethal hematopoietic acute radiation syndrome derived from studies that focused on total body irradiation and partial body irradiation with bone marrow sparing. The marked differential in estimated LD50/60 from 7.5 Gy to 10.88 Gy for the total body irradiation and partial body irradiation with 5% bone marrow sparing models, respectively, provided a clear distinction between the attendant multiple organ injury and natural history of the two models that included medical management. Total body irradiation was focused on equivalent LD50/60 exposures. The 10 Gy and 11 Gy partial body with 5% bone marrow sparing exposures bracketed the LD50/60 (10.88 Gy). The incidence, progression, and duration of multiple organ injury was described for each exposure protocol within the hematopoietic acute radiation syndrome. The higher threshold doses for the partial body irradiation with bone marrow sparing protocol induced a marked degree of multiple organ injury to include lethal gastrointestinal acute radiation syndrome, prolonged crypt loss and mucosal damage, immune suppression, acute kidney injury, body weight loss, and added clinical comorbidities that defined a complex timeline of organ injury through the acute hematopoietic acute radiation syndrome. The natural history of the acute radiation syndrome presents a 60-d time segment of multi-organ sequelae that is concomitant with the latent period or time to onset of the evolving multi-organ injury of the delayed effects of acute radiation exposure.

Published
2021

2. Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data

Author

Götz Thomalla, Florent Boutitie, Henry Ma, Masatoshi Koga, Peter Ringleb, Lee H Schwamm, Ona Wu, Martin Bendszus, Christopher F Bladin, Bruce C V Campbell, Bastian Cheng, Leonid Churilov, Martin Ebinger, Matthias Endres, Jochen B Fiebach, Mayumi Fukuda-Doi, Manabu Inoue, Timothy J Kleinig, Lawrence L Latour, Robin Lemmens, Christopher R Levi, Didier Leys, Kaori Miwa, Carlos A Molina, Keith W Muir, Norbert Nighoghossian, Mark W Parsons, Salvador Pedraza, Peter D Schellinger, Stefan Schwab, Claus Z Simonsen, Shlee S Song, Vincent Thijs, Danilo Toni, Chung Y Hsu, Nils Wahlgren, Haruko Yamamoto, Nawaf Yassi, Sohei Yoshimura, Steven Warach, Werner Hacke, Kazunori Toyoda, Geoffrey A Donnan, Stephen M Davis, Christian Gerloff, Boris Raul Acosta, Karen Aegidius, Christian Albiker, Anna Alegiani, Miriam Almendrote, Angelika Alonso, Katharina Althaus, Pierre Amarenco, Hemasse Amiri, Bettina Anders, Adriana Aniculaesei, Jason Appleton, Juan Arenillas, Christina Back, Christian Bähr, Jürgen Bardutzky, Flore Baronnet-Chauvet, Rouven Bathe-Peters, Anna Bayer-Karpinska, Juan L. Becerra, Christoph Beck, Olga Belchí Guillamon, Amandine Benoit, Nadia Berhoune, Daniela Bindila, Julia Birchenall, Karine Blanc-Lasserre, Miguel Blanco Gonzales, Tobias Bobinger, Ulf Bodechtel, Eric Bodiguel, Urszula Bojaryn, Louise Bonnet, Benjamin Bouamra, Paul Bourgeois, Lorenz Breuer, Ludovic Breynaert, David Broughton, Raf Brouns, Sébastian Brugirard, Bart Bruneel, Florian Buggle, Serkan Cakmak, Ana Calleja, David Calvet, David Carrera, Hsin-Chieh Chen, Bharath Cheripelli, Tae-Hee Cho, Chi-un Choe, Lillian Choy, Hanne Christensen, Mareva Ciatipis, Geoffrey Cloud, Julien Cogez, Elisa Cortijo, Sophie Crozier, Dorte Damgaard, Krishna Dani, Beatrijs De Coene, Isabel De Hollander, Jacques De Keyser, Nina De Klippel, Charlotte De Maeseneire, Ann De Smedt, Maria del Mar Castellanos Rodrigo, Sandrine Deltour, Jelle Demeestere, Laurent Derex, Philippe Desfontaines, Ralf Dittrich, Anand Dixit, Laurens Dobbels, Valérie Domigo, Laura Dorado, Charlotte Druart, Kristina Hougaard Dupont, Anne Dusart, Rainer Dziewas, Matthias Ebner, Myriam Edjali-Goujon, Philipp Eisele, Salwa El Tawil, Ahmed Elhfnawy, Ana Etexberria, Nicholas Evans, Simon Fandler, Franz Fazekas, Sandra Felix, Jochen B. Fiebach, Jens Fiehler, Alexandra Filipov, Katharina Filipski, Robert Fleischmann, Christian Foerch, Ian Ford, Alexandra Gaenslen, Ivana Galinovic, Elena Meseguer Gancedo, Ramanan Ganeshan, Carlos García Esperón, Alicia Garrido, Thomas Gattringer, Olivia Geraghty, Rohat Geran, Stefan Gerner, Sylvie Godon-Hardy, Jos Göhler, Amir Golsari, Meritxell Gomis, David Gorriz, Verena Gramse, Laia Grau, Martin Griebe, Cristina Guerrero, Damla Guerzoglu, Sophie Guettier, Vincent Guiraud, Christoph Gumbinger, Ignaz Gunreben, Florian Haertig, Christian Hametner, Bernard Hanseeuw, Andreas Hansen, Jakob Hansen, Thomas Harbo, Andreas Harloff, Peter Harmel, Karl Georg Häusler, Florian Heinen, Valentin Held, Simon Hellwig, Dimitri Hemelsoet, Michael Hennerici, Juliane Herm, Sylvia Hermans, María Hernández, Jose Hervas Vicente, Niels Hjort, Cristina Hobeanu, Carsten Hobohm, Elmar Höfner, Katharina Hohenbichler, Marc Hommel, Julia Hoppe, Eva Hornberger, Carolin Hoyer, Xuya Huang, Nils Ipsen, Irina Isern, Lourdes Ispierto, Helle Iversen, Lise Jeppesen, Marta Jimenez, Jan Jungehülsing, Eric Jüttler, Dheeraj Kalladka, Bernd Kallmünzer, Arindam Kar, Lars Kellert, André Kemmling, Tobias Kessler, Usman Khan, Matthias Klein, Christoph Kleinschnitz, Matti Klockziem, Michael Knops, Luzie Koehler, Martin Koehrmann, Heinz Kohlfürst, Rainer Kollmar, Peter Kraft, Thomas Krause, Bo Kristensen, Jan M. Kröber, Natalia Kurka, Alexandre Ladoux, Patrice Laloux, Catherine Lamy, Emmanuelle Landrault, Arne Lauer, Claire Lebely, Jonathan Leempoel, Kennedy Lees, Anne Leger, Laurence Legrand, Lin Li, Anna-Mareike Löbbe, Frederic London, Elena Lopez-cancio, Matthias Lorenz, Stephen Louw, Caroline Lovelock, Manuel Lozano Sánchez, Giuseppe Lucente, Janos Lückl, Alain Luna, Kosmas Macha, Alexandre Machet, Daniel Mackenrodt, Dominik Madzar, Charles Majoie, Anika Männer, Vicky Maqueda, Jacob Marstrand, Alicia Martinez, Annika Marzina, Laura Mechthouff, Per Meden, Guy Meersman, Julia Meier, Charles Mellerio, Oliver Menn, Nadja Meyer, Dominik Michalski, Peter Michels, Lene Michelsen, Monica Millán Torne, Jens Minnerup, Boris Modrau, Sebastian Moeller, Anette Møller, Nathalie Morel, Fiona Moreton, Ludovic Morin, Thierry Moulin, Barry Moynihan, Anne K. Mueller, Keith W. Muir, Patricia Mulero, Sibu Mundiyanapurath, Johannes Mutzenbach, Simon Nagel, Oliver Naggara, Arumugam Nallasivan, Irene Navalpotro, Alexander H. Nave, Paul Nederkoorn, Lars Neeb, Hermann Neugebauer, Tobias Neumann-Haefelin, Stefan Oberndorfer, Christian Opherk, Lorenz Oppel, Catherine Oppenheim, Johannes Orthgieß, Leif Ostergaard, Perrine Paindeville, Ernest Palomeras, Verena Panitz, Bhavni Patel, Andre Peeters, Dirk Peeters, Anna Pellisé, Johann Pelz, Anthony Pereira, Natalia Pérez de la Ossa, Richard Perry, Salvador Petraza, Stéphane Peysson, Waltraud Pfeilschifter, Alexander Pichler, Alexandra Pierskalla, Hans-Werner Pledl, Sven Poli, Katrin Pomrehn, Marika Poulsen, Luis Prats, Silvia Presas, Elisabeth Prohaska, Volker Puetz, Josep Puig, Josep Puig Alcántara, Jan Purrucker, Veronique Quenardelle, Sankaranarayanan Ramachandran, Soulliard Raphaelle, Nicolas Raposo, Tilman Reiff, Michel Remmers, Pauline Renou, Martin Ribitsch, Hardy Richter, Martin Ritter, Thomas Ritzenthaler, Gilles Rodier, Christine Rodriguez-Regent, Manuel Rodríguez-Yáñez, Maria Roennefarth, Christine Roffe, Sverre Rosenbaum, Charlotte Rosso, Joachim Röther, Michal Rozanski, Noelia Ruiz de Morales, Francesca Russo, Matthieu Rutgers, Sharmilla Sagnier, Yves Samson, Josep Sánchez, Tamara Sauer, Jan H. Schäfer, Simon Schieber, Josef Schill, Dennis Schlak, Ludwig Schlemm, Sein Schmidt, Wouter Schonewille, Julian Schröder, Andreas Schulz, Johannes Schurig, Sönke Schwarting, Alexander Schwarz, Christopher Schwarzbach, Matthias Seidel, Alexander Seiler, Jochen Sembill, Joaquin Serena Leal, Ashit Shetty, Igor Sibon, Claus Z. Simonsen, Oliver Singer, Aravinth Sivagnanaratham, Ide Smets, Craig Smith, Peter Soors, Nikola Sprigg, Maximilian Spruegel, David Stark, Susanne Steinert, Sebastian Stösser, Markus Stuermlinger, Bart Swinnen, Ruben Tamazyan, Jose Tembl, Mikel Terceno Izaga, Emmanuel Touze, Thomas Truelsen, Guillaume Turc, Gaetane Turine, Serdar Tütüncü, Pippa Tyrell, Xavier Ustrell, Wilfried Vadot, Anne-Evelyne Vallet, Pauline Vallet, Lucie van den Berg, Sophie van den Berg, Cecile van Eendenburg, Robbert-Jan Van Hooff, Isabelle van Sloten, Peter Vanacker, Evelien Vancaester, Patrick Vanderdonckt, Yves Vandermeeren, Frederik Vanhee, Roland Veltkamp, Karsten Vestergaard, Alain Viguier, Dolores Vilas, Kersten Villringer, Dieke Voget, Jörg von Schrader, Paul von Weitzel, Elisabeth Warburton, Claudia Weber, Jörg Weber, Karl Wegscheider, Mirko Wegscheider, Christian Weimar, Karin Weinstich, Christopher Weise, Gesa Weise, Chris Willems, Klemens Winder, Matthias Wittayer, Marc Wolf, Martin Wolf, Valerie Wolff, Christian Wollboldt, Frank Wollenweber, Anke Wouters, Bertrand Yalo, Marion Yger, Nadia Younan, Laetita Yperzeele, Vesna Zegarac, Pia Zeiner, Ulf Ziemann, Thomas Zonneveld, Mathieu Zuber, Tsugio Akutsu, Junya Aoki, Shuji Arakawa, Ryosuke Doijiri, Yusuke Egashira, Yukiko Enomoto, Eisuke Furui, Konosuke Furuta, Seiji Gotoh, Toshimitsu Hamasaki, Yasuhiro Hasegawa, Teryuki Hirano, Kazunari Homma, Masahiko Ichijyo, Toshihiro Ide, Shuichi Igarashi, Yasuyuki Iguchi, Masafumi Ihara, Hajime Ikenouchi, Tsuyoshi Inoue, Ryo Itabashi, Yasuhiro Ito, Toru Iwama, Kenji Kamiyama, Shoko Kamiyoshi, Haruka Kanai, Yasuhisa Kanematsu, Takao Kanzawa, Kazumi Kimura, Jiro Kitayama, Takanari Kitazono, Rei Kondo, Kohsuke Kudo, Masayoshi Kusumi, Ken Kuwahara, Shoji Matsumoto, Hideki Matsuoka, Ban Mihara, Kazuo Minematsu, Ken Miura, Naomi Morita, Wataru Mouri, Kayo Murata, Yoshinari Nagakane, Taizen Nakase, Hiromi Ohara, Nobuyuki Ohara, Hideyuki Ohnishi, Hajime Ohta, Masafumi Ohtaki, Ryo Ohtani, Toshiho Ohtsuki, Hideo Ohyama, Takashi Okada, Yasushi Okada, Masato Osaki, Nobuyuki Sakai, Yoshiki Sanbongi, Naoshi Sasaki, Makoto Sasaki, Shoichiro Sato, Kenta Seki, Wataru Shimizu, Yoshiaki Shiokawa, Takashi Sozu, Junichiro Suzuki, Rieko Suzuki, Yasushi Takagi, Shunya Takizawa, Norio Tanahashi, Eijiro Tanaka, Ryota Tanaka, Yohei Tateishi, Tomoaki Terada, Tadashi Terasaki, Kenichi Todo, Azusa Tokunaga, Akira Tsujino, Toshihiro Ueda, Yoshikazu Uesaka, Mihoko Uotani, Takao Urabe, Masao Watanabe, Yoshiki Yagita, Yusuke Yakushiji, Keizo Yasui, Toshiro Yonehara, Shinichi Yoshimura, K. Aarnio, F. Alemseged, C. Anderson, T. Ang, M.L. Archer, J. Attia, P. Bailey, A. Balabanski, A. Barber, P.A. Barber, J. Bernhardt, A. Bivard, D. Blacker, C.F. Bladin, A. Brodtmann, D. Cadilhac, B.C.V. Campbell, L. Carey, S. Celestino, L. Chan, W.H. Chang, A. ChangI, C.H. Chen, C.-I. Chen, H.F. Chen, T.C. Chen, W.H. Chen, Y.Y. Chen, C.A. Cheng, E. Cheong, Y.W. Chiou, P.M. Choi, H.J. Chu, C.S. Chuang, T.C. Chung, L. Churilov, B. Clissold, A. Connelly, S. Coote, B. Coulton, E. Cowley, J. Cranefield, S. Curtze, C. D'Este, S.M. Davis, S. Day, P.M. Desmond, H.M. Dewey, C. Ding, G.A. Donnan, R. Drew, S. Eirola, D. Field, T. Frost, C. Garcia-Esperon, K. George, R. Gerraty, R. Grimley, Y.C. Guo, G. Hankey, J. Harvey, S.C. Ho, K. Hogan, D. Howells, P.M. Hsiao, C.H. Hsu, C.T. Hsu, C.-S. Hsu, J.P. Hsu, Y.D. Hsu, Y.T. Hsu, C.J. Hu, C.C. Huang, H.Y. Huang, M.Y. Huang, S.C. Huang, W.S. Huang, D. Jackson, J.S. Jeng, S.K. Jiang, L. Kaauwai, O. Kasari, J. King, T.J. Kleinig, M. Koivu, J. Kolbe, M. Krause, C.W. Kuan, W.L. Kung, C. Kyndt, C.L. Lau, A. Lee, C.Y. Lee, J.T. Lee, Y. Lee, Y.C. Lee, C. Levi, C.R. Levi, L.M. Lien, J.C. Lim, C.C. Lin, C.H. Lin, C.M. Lin, D. Lin, C.H. Liu, J. Liu, Y.C. Lo, P.S. Loh, E. Low, C.H. Lu, C.J. Lu, M.K. Lu, J. Ly, H. Ma, L. Macaulay, R. Macdonnell, E. Mackey, M. Macleod, J. Mahadevan, V. Maxwell, R. McCoy, A. McDonald, S. McModie, A. Meretoja, S. Mishra, P.J. Mitchell, F. Miteff, A. Moore, C. Muller, F. Ng, F.C. Ng, J-L. Ng, W. O'Brian, V. O'Collins, T.J. Oxley, M.W. Parsons, S. Patel, G.S. Peng, L. Pesavento, T. Phan, E. Rodrigues, Z. Ross, A. Sabet, M. Sallaberger, P. Salvaris, D. Shah, G. Sharma, G. Sibolt, M. Simpson, S. Singhal, B. Snow, N. Spratt, R. Stark, J. Sturm, M.C. Sun, Y. Sun, P.S. Sung, Y.F. Sung, M. Suzuki, M. Tan, S.C. Tang, T. Tatlisumak, V. Thijs, M. Tiainen, C.H. Tsai, C.K. Tsai, C.L. Tsai, H.T. Tsai, L.K. Tsai, C.H. Tseng, L.T. Tseng, J. Tsoleridis, H. Tu, H.T-H. Tu, W. Vallat, J. Virta, W.C. Wang, Y.T. Wang, M. Waters, L. Weir, T. Wijeratne, C. Williams, W. Wilson, A.A. Wong, K. Wong, T.Y. Wu, Y.H. Wu, B. Yan, F.C. Yang, Y.W. Yang, N. Yassi, H.L. Yeh, J.H. Yeh, S.J. Yeh, C.H. Yen, D. Young, C.L. Ysai, W.W. Zhang, H. Zhao, L. Zhao, Katharina Althaus-Knaurer, Jörg Berrouschot, Erich Bluhmki, Paolo Bovi, Gilles Chatellier, Lynda Cove, Stephen Davis, A. Dixit, Geoffrey Donnan, Christina Ehrenkrona, Christoph Eschenfelder, Marc Fatar, Juan Francisco Arenillas, Franz Gruber, Lalit Kala, Peter Kapeller, Markku Kaste, Christof Kessler, Martin Köhrmann, Rico Laage, Kennedy R. Lees, Alain Luna Rodriguez, Jean-Louis Mas, Robert Mikulik, Carlos Molina, Girish Muddegowda, Keith Muir, Kurt Niederkorn, Xavier Nuñez, Peter Schellinger, Joaquin Serena, Jan Sobesky, Thorsten Steiner, Ann-Sofie Svenson, Rüdiger von Kummer, Joanna Wardlaw, Rebecca A. Betensky, Gregoire Boulouis, Raphael A. Carandang, William A. Copen, Pedro Cougo, Shawna Cutting, Kendra Drake, Andria L. Ford, John Hallenbeck, Gordon J. Harris, Robert Hoesch, Amie Hsia, Carlos Kase, Lawrence Latour, Michael H. Lev, Alona Muzikansky, Nandakumar Nagaraja, Lee H. Schwamm, Eric Searls, Shlee S. Song, Sidney Starkman, Albert J. Yoo, Ramin Zand, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Hospices Civils de Lyon (HCL), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon, Monash University [Melbourne], National Cerebral and Cardiovascular Center (NCCC - OSAKA), Osaka University [Osaka], University of Heidelberg, Medical Faculty, Massachusetts General Hospital [Boston], University of Melbourne, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Royal Adelaide Hospital [Adelaide Australia], National Institute of Neurological Disorders and Stroke [Bethesda] (NINDS), National Institutes of Health [Bethesda] (NIH), University Hospitals Leuven [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Flanders Make [Leuven], Flanders Make, University of Newcastle [Australia] (UoN), Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Vall d'Hebron University Hospital [Barcelona], University of Glasgow, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Girona Biomedical Research Institute [Girona, Spain] (IDIBGI), Ruhr-Universität Bochum [Bochum], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Aarhus University Hospital, Cedars-Sinai Medical Center, Florey Institute of Neuroscience and Mental Health [Melbourne, Victoria, Australia], Austin Health, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], China Medical University Hospital [Taichung], Karolinska Institutet [Stockholm], The Walter and Eliza Hall Institute of Medical Research (WEHI), University of Texas at Austin [Austin], Collaborators Evaluation of unknown Onset Stroke thrombolysis trials (EOS) investigators: Boris Raul Acosta, Karen Aegidius, Christian Albiker, Anna Alegiani, Miriam Almendrote, Angelika Alonso, Katharina Althaus, Pierre Amarenco, Hemasse Amiri, Bettina Anders, Adriana Aniculaesei, Jason Appleton, Juan Arenillas, Christina Back, Christian Bähr, Jürgen Bardutzky, Flore Baronnet-Chauvet, Rouven Bathe-Peters, Anna Bayer-Karpinska, Juan L Becerra, Christoph Beck, Olga Belchí Guillamon, Amandine Benoit, Nadia Berhoune, Daniela Bindila, Julia Birchenall, Karine Blanc-Lasserre, Miguel Blanco Gonzales, Tobias Bobinger, Ulf Bodechtel, Eric Bodiguel, Urszula Bojaryn, Louise Bonnet, Benjamin Bouamra, Paul Bourgeois, Florent Boutitie, Lorenz Breuer, Ludovic Breynaert, David Broughton, Raf Brouns, Sébastian Brugirard, Bart Bruneel, Florian Buggle, Serkan Cakmak, Ana Calleja, David Calvet, David Carrera, Hsin-Chieh Chen, Bastian Cheng, Bharath Cheripelli, Tae-Hee Cho, Chi-Un Choe, Lillian Choy, Hanne Christensen, Mareva Ciatipis, Geoffrey Cloud, Julien Cogez, Elisa Cortijo, Sophie Crozier, Dorte Damgaard, Krishna Dani, Beatrijs De Coene, Isabel De Hollander, Jacques De Keyser, Nina De Klippel, Charlotte De Maeseneire, Ann De Smedt, Maria Del Mar Castellanos Rodrigo, Sandrine Deltour, Jelle Demeestere, Laurent Derex, Philippe Desfontaines, Ralf Dittrich, Anand Dixit, Laurens Dobbels, Valérie Domigo, Laura Dorado, Charlotte Druart, Kristina Hougaard Dupont, Anne Dusart, Rainer Dziewas, Martin Ebinger, Matthias Ebner, Myriam Edjali-Goujon, Philipp Eisele, Salwa El Tawil, Ahmed Elhfnawy, Matthias Endres, Ana Etexberria, Nicholas Evans, Simon Fandler, Franz Fazekas, Sandra Felix, Jochen B Fiebach, Jens Fiehler, Alexandra Filipov, Katharina Filipski, Robert Fleischmann, Christian Foerch, Ian Ford, Alexandra Gaenslen, Ivana Galinovic, Elena Meseguer Gancedo, Ramanan Ganeshan, Carlos García Esperón, Alicia Garrido, Thomas Gattringer, Olivia Geraghty, Rohat Geran, Christian Gerloff, Stefan Gerner, Sylvie Godon-Hardy, Jos Göhler, Amir Golsari, Meritxell Gomis, David Gorriz, Verena Gramse, Laia Grau, Martin Griebe, Cristina Guerrero, Damla Guerzoglu, Sophie Guettier, Vincent Guiraud, Christoph Gumbinger, Ignaz Gunreben, Florian Haertig, Christian Hametner, Bernard Hanseeuw, Andreas Hansen, Jakob Hansen, Thomas Harbo, Andreas Harloff, Peter Harmel, Karl Georg Häusler, Florian Heinen, Valentin Held, Simon Hellwig, Dimitri Hemelsoet, Michael Hennerici, Juliane Herm, Sylvia Hermans, María Hernández, Jose Hervas Vicente, Niels Hjort, Cristina Hobeanu, Carsten Hobohm, Elmar Höfner, Katharina Hohenbichler, Marc Hommel, Julia Hoppe, Eva Hornberger, Carolin Hoyer, Xuya Huang, Nils Ipsen, Irina Isern, Lourdes Ispierto, Helle Iversen, Lise Jeppesen, Marta Jimenez, Jan Jungehülsing, Eric Jüttler, Dheeraj Kalladka, Bernd Kallmünzer, Arindam Kar, Lars Kellert, André Kemmling, Tobias Kessler, Usman Khan, Matthias Klein, Christoph Kleinschnitz, Matti Klockziem, Michael Knops, Luzie Koehler, Martin Koehrmann, Heinz Kohlfürst, Rainer Kollmar, Peter Kraft, Thomas Krause, Bo Kristensen, Jan M Kröber, Natalia Kurka, Alexandre Ladoux, Patrice Laloux, Catherine Lamy, Emmanuelle Landrault, Arne Lauer, Claire Lebely, Jonathan Leempoel, Kennedy Lees, Anne Leger, Laurence Legrand, Robin Lemmens, Lin Li, Anna-Mareike Löbbe, Frederic London, Elena Lopez-Cancio, Matthias Lorenz, Stephen Louw, Caroline Lovelock, Manuel Lozano Sánchez, Giuseppe Lucente, Janos Lückl, Alain Luna, Kosmas Macha, Alexandre Machet, Daniel Mackenrodt, Dominik Madzar, Charles Majoie, Anika Männer, Vicky Maqueda, Jacob Marstrand, Alicia Martinez, Annika Marzina, Laura Mechthouff, Per Meden, Guy Meersman, Julia Meier, Charles Mellerio, Oliver Menn, Nadja Meyer, Dominik Michalski, Peter Michels, Lene Michelsen, Monica Millán Torne, Jens Minnerup, Boris Modrau, Sebastian Moeller, Anette Møller, Nathalie Morel, Fiona Moreton, Ludovic Morin, Thierry Moulin, Barry Moynihan, Anne K Mueller, Keith W Muir, Patricia Mulero, Sibu Mundiyanapurath, Johannes Mutzenbach, Simon Nagel, Oliver Naggara, Arumugam Nallasivan, Irene Navalpotro, Alexander H Nave, Paul Nederkoorn, Lars Neeb, Hermann Neugebauer, Tobias Neumann-Haefelin, Norbert Nighoghossian, Stefan Oberndorfer, Christian Opherk, Lorenz Oppel, Catherine Oppenheim, Johannes Orthgieß, Leif Ostergaard, Perrine Paindeville, Ernest Palomeras, Verena Panitz, Bhavni Patel, Andre Peeters, Dirk Peeters, Anna Pellisé, Johann Pelz, Anthony Pereira, Natalia Pérez de la Ossa, Richard Perry, Salvador Petraza, Stéphane Peysson, Waltraud Pfeilschifter, Alexander Pichler, Alexandra Pierskalla, Hans-Werner Pledl, Sven Poli, Katrin Pomrehn, Marika Poulsen, Luis Prats, Silvia Presas, Elisabeth Prohaska, Volker Puetz, Josep Puig, Josep Puig Alcántara, Jan Purrucker, Veronique Quenardelle, Sankaranarayanan Ramachandran, Soulliard Raphaelle, Nicolas Raposo, Tilman Reiff, Michel Remmers, Pauline Renou, Martin Ribitsch, Hardy Richter, Peter Ringleb, Martin Ritter, Thomas Ritzenthaler, Gilles Rodier, Christine Rodriguez-Regent, Manuel Rodríguez-Yáñez, Maria Roennefarth, Christine Roffe, Sverre Rosenbaum, Charlotte Rosso, Joachim Röther, Michal Rozanski, Noelia Ruiz de Morales, Francesca Russo, Matthieu Rutgers, Sharmilla Sagnier, Yves Samson, Josep Sánchez, Tamara Sauer, Jan H Schäfer, Simon Schieber, Josef Schill, Dennis Schlak, Ludwig Schlemm, Sein Schmidt, Wouter Schonewille, Julian Schröder, Andreas Schulz, Johannes Schurig, Sönke Schwarting, Alexander Schwarz, Christopher Schwarzbach, Matthias Seidel, Alexander Seiler, Jochen Sembill, Joaquin Serena Leal, Ashit Shetty, Igor Sibon, Claus Z Simonsen, Oliver Singer, Aravinth Sivagnanaratham, Ide Smets, Craig Smith, Peter Soors, Nikola Sprigg, Maximilian Spruegel, David Stark, Susanne Steinert, Sebastian Stösser, Markus Stuermlinger, Bart Swinnen, Ruben Tamazyan, Jose Tembl, Mikel Terceno Izaga, Vincent Thijs, Götz Thomalla, Emmanuel Touze, Thomas Truelsen, Guillaume Turc, Gaetane Turine, Serdar Tütüncü, Pippa Tyrell, Xavier Ustrell, Wilfried Vadot, Anne-Evelyne Vallet, Pauline Vallet, Lucie van den Berg, Sophie van den Berg, Cecile van Eendenburg, Robbert-Jan Van Hooff, Isabelle van Sloten, Peter Vanacker, Evelien Vancaester, Patrick Vanderdonckt, Yves Vandermeeren, Frederik Vanhee, Roland Veltkamp, Karsten Vestergaard, Alain Viguier, Dolores Vilas, Kersten Villringer, Dieke Voget, Jörg von Schrader, Paul von Weitzel, Elisabeth Warburton, Claudia Weber, Jörg Weber, Karl Wegscheider, Mirko Wegscheider, Christian Weimar, Karin Weinstich, Christopher Weise, Gesa Weise, Chris Willems, Klemens Winder, Matthias Wittayer, Marc Wolf, Martin Wolf, Valerie Wolff, Christian Wollboldt, Frank Wollenweber, Anke Wouters, Bertrand Yalo, Marion Yger, Nadia Younan, Laetita Yperzeele, Vesna Zegarac, Pia Zeiner, Ulf Ziemann, Thomas Zonneveld, Mathieu Zuber, Tsugio Akutsu, Junya Aoki, Junya Aoki, Shuji Arakawa, Ryosuke Doijiri, Yusuke Egashira, Yukiko Enomoto, Mayumi Fukuda-Doi, Eisuke Furui, Konosuke Furuta, Seiji Gotoh, Toshimitsu Hamasaki, Yasuhiro Hasegawa, Teryuki Hirano, Kazunari Homma, Masahiko Ichijyo, Toshihiro Ide, Shuichi Igarashi, Yasuyuki Iguchi, Masafumi Ihara, Hajime Ikenouchi, Manabu Inoue, Tsuyoshi Inoue, Ryo Itabashi, Yasuhiro Ito, Toru Iwama, Kenji Kamiyama, Shoko Kamiyoshi, Haruka Kanai, Yasuhisa Kanematsu, Takao Kanzawa, Kazumi Kimura, Jiro Kitayama, Takanari Kitazono, Masatoshi Koga, Rei Kondo, Kohsuke Kudo, Masayoshi Kusumi, Ken Kuwahara, Shoji Matsumoto, Hideki Matsuoka, Ban Mihara, Kazuo Minematsu, Ken Miura, Kaori Miwa, Naomi Morita, Wataru Mouri, Kayo Murata, Yoshinari Nagakane, Taizen Nakase, Hiromi Ohara, Nobuyuki Ohara, Hideyuki Ohnishi, Hajime Ohta, Masafumi Ohtaki, Ryo Ohtani, Toshiho Ohtsuki, Hideo Ohyama, Takashi Okada, Yasushi Okada, Masato Osaki, Nobuyuki Sakai, Yoshiki Sanbongi, Naoshi Sasaki, Makoto Sasaki, Shoichiro Sato, Kenta Seki, Wataru Shimizu, Yoshiaki Shiokawa, Takashi Sozu, Junichiro Suzuki, Rieko Suzuki, Yasushi Takagi, Shunya Takizawa, Norio Tanahashi, Eijiro Tanaka, Ryota Tanaka, Yohei Tateishi, Tomoaki Terada, Tadashi Terasaki, Kenichi Todo, Azusa Tokunaga, Kazunori Toyoda, Akira Tsujino, Toshihiro Ueda, Yoshikazu Uesaka, Mihoko Uotani, Takao Urabe, Masao Watanabe, Yoshiki Yagita, Yusuke Yakushiji, Haruko Yamamoto, Keizo Yasui, Toshiro Yonehara, Sohei Yoshimura, Shinichi Yoshimura, K Aarnio, F Alemseged, C Anderson, T Ang, M L Archer, J Attia, P Bailey, A Balabanski, A Barber, P A Barber, J Bernhardt, A Bivard, D Blacker, C F Bladin, A Brodtmann, D Cadilhac, B C V Campbell, L Carey, S Celestino, L Chan, W H Chang, A ChangI, C H Chen, C-I Chen, H F Chen, T C Chen, W H Chen, Y Y Chen, C A Cheng, E Cheong, Y W Chiou, P M Choi, H J Chu, C S Chuang, T C Chung, L Churilov, B Clissold, A Connelly, S Coote, B Coulton, E Cowley, J Cranefield, S Curtze, C D'Este, S M Davis, S Day, P M Desmond, H M Dewey, C Ding, G A Donnan, R Drew, S Eirola, D Field, T Frost, C Garcia-Esperon, K George, R Gerraty, R Grimley, Y C Guo, G Hankey, J Harvey, S C Ho, K Hogan, D Howells, P M Hsiao, C H Hsu, C T Hsu, C-S Hsu, J P Hsu, Y D Hsu, Y T Hsu, C J Hu, C C Huang, H Y Huang, M Y Huang, S C Huang, W S Huang, D Jackson, J S Jeng, S K Jiang, L Kaauwai, O Kasari, J King, T J Kleinig, M Koivu, J Kolbe, M Krause, C W Kuan, W L Kung, C Kyndt, C L Lau, A Lee, C Y Lee, J T Lee, Y Lee, Y C Lee, C Levi, C R Levi, L M Lien, J C Lim, C C Lin, C H Lin, C M Lin, D Lin, C H Liu, J Liu, Y C Lo, P S Loh, E Low, C H Lu, C J Lu, M K Lu, J Ly, H Ma, L Macaulay, R Macdonnell, E Mackey, M Macleod, J Mahadevan, V Maxwell, R McCoy, A McDonald, S McModie, A Meretoja, S Mishra, P J Mitchell, F Miteff, A Moore, C Muller, F Ng, F C Ng, J-L Ng, W O'Brian, V O'Collins, T J Oxley, M W Parsons, S Patel, G S Peng, L Pesavento, T Phan, E Rodrigues, Z Ross, A Sabet, M Sallaberger, P Salvaris, D Shah, G Sharma, G Sibolt, M Simpson, S Singhal, B Snow, N Spratt, R Stark, J Sturm, M C Sun, Y Sun, P S Sung, Y F Sung, M Suzuki, M Tan, S C Tang, T Tatlisumak, V Thijs, M Tiainen, C H Tsai, C K Tsai, C L Tsai, H T Tsai, L K Tsai, C H Tseng, L T Tseng, J Tsoleridis, H Tu, H T-H Tu, W Vallat, J Virta, W C Wang, Y T Wang, M Waters, L Weir, T Wijeratne, C Williams, W Wilson, A A Wong, K Wong, T Y Wu, Y H Wu, B Yan, F C Yang, Y W Yang, N Yassi, H L Yeh, J H Yeh, S J Yeh, C H Yen, D Young, C L Ysai, W W Zhang, H Zhao, L Zhao, Katharina Althaus-Knaurer, Martin Bendszus, Jörg Berrouschot, Erich Bluhmki, Paolo Bovi, Gilles Chatellier, Lynda Cove, Stephen Davis, A Dixit, Geoffrey Donnan, Rainer Dziewas, Christina Ehrenkrona, Christoph Eschenfelder, Marc Fatar, Juan Francisco Arenillas, Franz Gruber, Werner Hacke, Lalit Kala, Peter Kapeller, Markku Kaste, Christof Kessler, Martin Köhrmann, Rico Laage, Kennedy R Lees, Didier Leys, Alain Luna Rodriguez, Jean-Louis Mas, Robert Mikulik, Carlos Molina, Girish Muddegowda, Keith Muir, Kurt Niederkorn, Xavier Nuñez, Catherine Oppenheim, Sven Poli, Peter Ringleb, Peter Schellinger, Stefan Schwab, Joaquin Serena, Jan Sobesky, Thorsten Steiner, Ann-Sofie Svenson, Danilo Toni, Roland Veltkamp, Rüdiger von Kummer, Nils Wahlgren, Joanna Wardlaw, Rebecca A Betensky, Gregoire Boulouis, Raphael A Carandang, William A Copen, Pedro Cougo, Shawna Cutting, Kendra Drake, Andria L Ford, John Hallenbeck, Gordon J Harris, Robert Hoesch, Amie Hsia, Carlos Kase, Lawrence Latour, Arne Lauer, Michael H Lev, Alona Muzikansky, Nandakumar Nagaraja, Lee H Schwamm, Eric Searls, Shlee S Song, Sidney Starkman, Steven Warach, Ona Wu, Albert J Yoo, Ramin Zand, University of Newcastle [Callaghan, Australia] (UoN), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CarMeN, laboratoire, Yperzeele, Laetitia, Evaluation of Unknown Onset Stroke Thrombolysis trials (EOS) investigators, UCL - SSS/IONS - Institute of NeuroScience, UCL - (MGD) Service de neurologie, Supporting clinical sciences, UZB Other, Physical Medicine and Rehabilitation, Clinical sciences, Neuroprotection & Neuromodulation, Radiology and Nuclear Medicine, ANS - Neurovascular Disorders, Neurology, ACS - Atherosclerosis & ischemic syndromes, Graduate School, Center of Experimental and Molecular Medicine, ACS - Pulmonary hypertension & thrombosis, and ACS - Microcirculation

Subjects
medicine.medical_treatment, [SDV]Life Sciences [q-bio], Ischemic Stroke/*diagnostic imaging/*drug therapy, Tomography, X-Ray Computed/methods, Fibrinolytic Agents/adverse effects/*therapeutic use, 030204 cardiovascular system & hematology, Ischemic Stroke/diagnostic imaging, surgery, 0302 clinical medicine, Modified Rankin Scale, 030212 general & internal medicine, 10. No inequality, Infusions, Intravenous, Stroke, Tomography, Time-to-Treatment, General Medicine, Thrombolysis, X-Ray Computed/methods, Tissue Plasminogen Activator/adverse effects, 3. Good health, [SDV] Life Sciences [q-bio], Diffusion Magnetic Resonance Imaging/methods, Treatment Outcome, Meta-analysis, Tissue Plasminogen Activator, Intravenous, medicine.medical_specialty, Infusions, Intravenous thrombolysis, Neuroimaging, Neuroscience(all), Placebo, Tissue Plasminogen Activator/adverse effects/*therapeutic use, 03 medical and health sciences, Fibrinolytic Agents, Internal medicine, medicine, Humans, ddc:610, Ischemic Stroke, business.industry, neurology, Fibrinolytic Agents/adverse effects, Odds ratio, Recovery of Function, medicine.disease, Clinical research, Diffusion Magnetic Resonance Imaging, Human medicine, business, Tomography, X-Ray Computed, Fibrinolytic agent
Abstract

International audience; BACKGROUND: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers. METHODS: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0-1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0-2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4-6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903. FINDINGS: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10-2·03]; p=0·011), with low heterogeneity across studies (I(2)=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05-1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06-2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4-6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52-1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03-4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [\textless1%], adjusted OR 5·58 [1·22-25·50]; p=0·024). INTERPRETATION: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death. FUNDING: None.

Published
2020

3. MALDI-MSI spatially maps N-glycan alterations to histologically distinct pulmonary pathologies following irradiation

Author

Maureen A. Kane, Thomas J. MacVittie, Claire L. Carter, Kim G. Hankey, George A. Parker, and Ann M. Farese

Subjects
0301 basic medicine, Male, Pathology, medicine.medical_specialty, Glycosylation, Pulmonary Fibrosis, lcsh:Medicine, Inflammation, Lung injury, Article, Imaging, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Fibrosis, Polysaccharides, Edema, Macrophages, Alveolar, medicine, Animals, lcsh:Science, Radiation Injuries, Lung, Pneumonitis, Multidisciplinary, Mass spectrometry, business.industry, Macrophages, lcsh:R, Cancer, Lung Injury, Pneumonia, Hyperplasia, medicine.disease, Macaca mulatta, 030104 developmental biology, Phenotype, chemistry, 030220 oncology & carcinogenesis, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, lcsh:Q, medicine.symptom, business, Mannose
Abstract

Radiation-induced lung injury is a highly complex combination of pathological alterations that develop over time and severity of disease development is dose-dependent. Following exposures to lethal doses of irradiation, morbidity and mortality can occur due to a combination of edema, pneumonitis and fibrosis. Protein glycosylation has essential roles in a plethora of biological and immunological processes. Alterations in glycosylation profiles have been detected in diseases ranging from infection, inflammation and cancer. We utilized mass spectrometry imaging to spatially map N-glycans to distinct pathological alterations during the clinically latent period and at 180 days post-exposure to irradiation. Results identified alterations in a number of high mannose, hybrid and complex N-glycans that were localized to regions of mucus and alveolar-bronchiolar hyperplasia, proliferations of type 2 epithelial cells, accumulations of macrophages, edema and fibrosis. The glycosylation profiles indicate most alterations occur prior to the onset of clinical symptoms as a result of pathological manifestations. Alterations in five N-glycans were identified as a function of time post-exposure. Understanding the functional roles N-glycans play in the development of these pathologies, particularly in the accumulation of macrophages and their phenotype, may lead to new therapeutic avenues for the treatment of radiation-induced lung injury.

Published
2020

4. Successful transfer of anti-SARS-CoV-2 immunity using convalescent plasma in an MM patient with hypogammaglobulinemia and COVID-19

Author

Djordje Atanackovic, Ryan A. Metcalf, Patricia R. Slev, Adam M. Spivak, Robert C. Blaylock, Vicente Planelles, Mohammad M. Sajadi, Yue Zheng, Heather D. Mannuel, Erin T. Larragoite, Mary Steinbach, Aaron P. Rapoport, Tim Luetkens, Emily S Spivak, Thomas B. Martins, Kim G. Hankey, and Stephanie V. Avila

Subjects
viruses, Pneumonia, Viral, 030204 cardiovascular system & hematology, Antibodies, Viral, Immunoglobulin G, Hypogammaglobulinemia, 03 medical and health sciences, Betacoronavirus, 0302 clinical medicine, Immunity, Agammaglobulinemia, medicine, Humans, 030212 general & internal medicine, skin and connective tissue diseases, Pandemics, Multiple myeloma, COVID-19 Serotherapy, Aged, biology, business.industry, SARS-CoV-2, fungi, Immunization, Passive, COVID-19, Hematology, biochemical phenomena, metabolism, and nutrition, medicine.disease, body regions, Pneumonia, Immunoglobulin M, Humoral immunity, Immunology, biology.protein, Female, Exceptional Case Report, Antibody, business, Coronavirus Infections, Multiple Myeloma
Abstract

Key Points A severely immunocompromised patient with MM and COVID19 who received a convalescent plasma product showed SARS-CoV-2 clearance. The convalescent plasma showed humoral immunity against all structural SARS-CoV-2 proteins, which was successfully transferred to the patient.

Published
2020

5. Acute and Chronic Kidney Injury in a Non-Human Primate Model of Partial-Body Irradiation with Bone Marrow Sparing

Author

Eric P. Cohen, Kim G. Hankey, Alexander Bennett, Ann M. Farese, George A. Parker, and Thomas J. MacVittie

Subjects
Male, Radiation Nephropathy, medicine.medical_specialty, Biophysics, Renal function, Kaplan-Meier Estimate, Kidney, Radiation Dosage, Dexamethasone, Article, Blood Urea Nitrogen, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Species Specificity, Bone Marrow, Animals, Medicine, Radiology, Nuclear Medicine and imaging, Organ Sparing Treatments, Blood urea nitrogen, Radiation, business.industry, Acute kidney injury, Acute Radiation Syndrome, Dose-Response Relationship, Radiation, medicine.disease, Combined Modality Therapy, Macaca mulatta, Anti-Bacterial Agents, Surgery, Radiation Injuries, Experimental, medicine.anatomical_structure, Creatinine, 030220 oncology & carcinogenesis, Anesthesia, Acute Disease, Chronic Disease, Models, Animal, Experimental pathology, Bone marrow, business
Abstract

The development of medical countermeasures against acute and delayed multi-organ injury requires animal models predictive of the human response to radiation and its treatment. Late chronic injury is a well-known feature of radiation nephropathy, but acute kidney injury has not been reported in an appropriate animal model. We have established a single-fraction partial-body irradiation model with minimal marrow sparing in non-human primates. Subject-based medical management was used including parenteral fluids according to prospective morbidity criteria. We show herein that 10 or 11 Gy exposures caused both acute and chronic kidney injury. Acute and chronic kidney injury appear to be dose-independent between 10 and 11 Gy. Acute kidney injury was identified during the first 50 days postirradiation and appeared to resolve before the occurrence of chronic kidney injury, which was progressively more severe up to 180 days postirradiation, which was the end of the study. These findings show that mitigation of the acute radiation syndrome by medical management will unmask delayed late effects that occur months after partial-body irradiation. They further emphasize that both acute and chronic changes in kidney function must be taken into account in the use and timing of mitigators and medical management for acute radiation syndrome and delayed effects of acute radiation exposure (DEARE).

Published
2017

6. Efficacy of Neulasta(®) or Neupogen(®) on H- and GI-ARS mortality and hematopoietic recovery in nonhuman primates after 10 Gy irradiation with 2.5% bone marrow sparing

Author

Thomas J. MacVittie, Karl Prado, Alexander Bennett, William E. Jackson, Allison Gibbs, Kim G. Hankey, and Ann M. Farese

Subjects
Male, medicine.medical_specialty, Filgrastim, Epidemiology, Health, Toxicology and Mutagenesis, Urology, Context (language use), Granulocyte, Neutropenia, Article, 030218 nuclear medicine & medical imaging, Polyethylene Glycols, 03 medical and health sciences, 0302 clinical medicine, Bone Marrow, medicine, Animals, Radiology, Nuclear Medicine and imaging, business.industry, Acute Radiation Syndrome, medicine.disease, Macaca mulatta, Hematopoiesis, Gastrointestinal Tract, Haematopoiesis, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Concomitant, Absolute neutrophil count, Hematinics, Bone marrow, business
Abstract

A nonhuman primate model of acute, partial-body, high-dose irradiation with minimal (2.5%) bone marrow sparing was used to assess endogenous gastrointestinal and hematopoietic recovery and the ability of Neulasta (pegylated granulocyte colony-stimulating factor) or Neupogen (granulocyte colony-stimulating factor) to enhance recovery from myelosuppression when administered at an increased interval between exposure and initiation of treatment. A secondary objective was to assess the effect of Neulasta or Neupogen on mortality and morbidity due to the hematopoietic acute radiation syndrome and concomitant gastrointestinal acute radiation syndrome. Nonhuman primates were exposed to 10.0 Gy, 6 MV, linear accelerator-derived photons delivered at 0.80 Gy min. All nonhuman primates received subject-based medical management. Nonhuman primates were dosed daily with control article (5% dextrose in water), initiated on day 1 postexposure; Neulasta (300 μg kg), administered on days 1, 8, and 15 or days 3, 10, and 17 postexposure; or Neupogen (10 μg kg), administered daily postexposure following its initiation on day 1 or day 3 until neutrophil recovery (absolute neutrophil count ≥1,000 cells μL for 3 consecutive days). Mortality in the irradiated cohorts suggested that administration of Neulasta or Neupogen on either schedule did not affect mortality due to gastrointestinal acute radiation syndrome or mitigate mortality due to hematopoietic acute radiation syndrome (plus gastrointestinal damage). Following 10.0 Gy partial-body irradiation with 2.5% bone marrow sparing, the mean duration of neutropenia (absolute neutrophil count

Published
2019

7. Increased Expression of Connective Tissue Growth Factor (CTGF) in Multiple Organs After Exposure of Non-Human Primates (NHP) to Lethal Doses of Radiation

Author

Thomas J. MacVittie, Kim G. Hankey, Cassandra P. Smith, Allison Gibbs, Pei Zhang, Cheryl Taylor-Howell, Wanchang Cui, and Sean R. Kearney

Subjects
Male, Pathology, medicine.medical_specialty, Epidemiology, Health, Toxicology and Mutagenesis, medicine.medical_treatment, Connective tissue, Spleen, Biology, Article, Lethal Dose 50, Fibrosis, medicine, Animals, Humans, Radiology, Nuclear Medicine and imaging, Radiometry, Kidney, Lung, integumentary system, Growth factor, Connective Tissue Growth Factor, Dose-Response Relationship, Radiation, Radiation Exposure, medicine.disease, Macaca mulatta, humanities, Up-Regulation, CTGF, Disease Models, Animal, Viscera, medicine.anatomical_structure, Organ Specificity, Immunohistochemistry
Abstract

Exposure to sufficiently high doses of ionizing radiation is known to cause fibrosis in many different organs and tissues. Connective tissue growth factor (CTGF/CCN2), a member of the CCN family of matricellular proteins, plays an important role in the development of fibrosis in multiple organs. The aim of the present study was to quantify the gene and protein expression of CTGF in a variety of organs from non-human primates (NHP) that were previously exposed to potentially lethal doses of radiation. Tissues from non-irradiated NHP and NHP exposed to whole thoracic lung irradiation (WTLI) or partial-body irradiation with 5% bone marrow sparing (PBI/BM5) were examined by real-time quantitative reverse transcription PCR, western blot, and immunohistochemistry. Expression of CTGF was elevated in the lung tissues of NHP exposed to WTLI relative to the lung tissues of the non-irradiated NHP. Increased expression of CTGF was also observed in multiple organs from NHP exposed to PBI/BM5 compared to non-irradiated NHP; these included the lung, kidney, spleen, thymus, and liver. These irradiated organs also exhibited histological evidence of increased collagen deposition compared to the control tissues. There was significant correlation of CTGF expression with collagen deposition in the lung and spleen of NHP exposed to PBI/BM5. Significant correlations were observed between spleen and multiple organs on CTGF expression and collagen deposition, respectively, suggesting possible crosstalk between spleen and other organs. These data suggest that CTGF levels are increased in multiple organs after radiation exposure and that inflammatory cell infiltration may contribute to the elevated levels of CTGF in multiple organs.

Published
2015

8. Rivaroxaban or aspirin for patent foramen ovale and embolic stroke of undetermined source: a prespecified subgroup analysis from the NAVIGATE ESUS trial

Author

Scott E Kasner, Balakumar Swaminathan, Pablo Lavados, Mukul Sharma, Keith Muir, Roland Veltkamp, Sebastian F Ameriso, Matthias Endres, Helmi Lutsep, Steven R Messé, J David Spence, Krassen Nedeltechev, Kanjana Perera, Gustavo Santo, Veronica Olavarria, Arne Lindgren, Shrikant Bangdiwala, Ashkan Shoamanesh, Scott D Berkowitz, Hardi Mundl, Stuart J Connolly, Robert G Hart, N Abdelhamid, D Abdul Rahman, M Abdul-Saheb, P Abreu, M Abroskina, F Abu Ahmad, S Accassat, M Acciaresi, A Adami, N Ahmad, F Ahmed, M Alberto Hawkes, F Alemseged, A Ali, R Altavilla, L Alwis, P Amarenco, S Amaro, LE Amaya Sanchez, A Amelia Pinto, SF Ameriso, H Amin, T Amino, AK Amjad, E Anagnostou, G Andersen, C Anderson, DC Anderson, M Andrea Falco, F Andres Mackinnon, D Andreu, M Androulakis, M Angel Gamero, G Angel Saredo, R Angeles Diaz, M Angels Font, S Anticoli, A Arauz, AA Arauz Gongora, P Araya, JF Arenillas Lara, S Arias Rivas, M Arnold, S Augustin, W Avelar, E Azevedo, V Babikian, A Bacellar, K Badalyan, HJ Bae, EM Baez Martinez, H Bagelmann, P Bailey, Z Bak, M Baker, A Balazs, D Baldaranov, I Balogun, T Balueva, Z Bankuti, M Bar, A Baranowska, J Bardutzky, S Barker Trejo, J Barlinn, F Baronnet, C Barroso, M Barteys, T Bartolottiova, A Barulin, M Bas, S Bashir, V Basile, R Bathe-Peters, R Bathula, C Batista, H Batur Caglayan, P Baumgartner, R Bazan, O Bazhenova, M Beaudry, J Beer, Y Behnam, C Beilei, A Beinlich, Y Bejot, A Belkin, OR Benavente, A Benjamin, V Berardi, D Bereczki, SD Berkowitz, J Berlingieri, W Berrios, J Berrouschot, M Bhandari, M Bhargavah, H Bicker, T Bicsak, M Bilik, D Bindila, J Birchenall, L Birnbaum, T Black, D Blacker, D Blacquiere, C Blanc-Labarre, C Blank, B Blazejewska-Hyzorek, S Bloch, E Bodiguel, E Bogdanov, L Boos, L Borcsik, N Bornstein, S Bouly, G Braga, I Bragado, MC Bravi, C Brokalaki, W Brola, R Brouns, D Bruce, J Brzoska-Mizgalska, B Buck, M Buksinska-Lisik, J Burke, M Burn, G Bustamante, L Cabrejo, K Cai, S Cajaraville, M Calejo, D Calvet, J Campillo, E Campos Costa, P Camps, H Can Alaydin, E Candeloro, C Canepa, CG Cantu Brito, M Cappellari, C Carcel, P Cardona Portela, F Cardoso, M Carek, M Carletti, J Carlos Portilla, P Caruso, I Casado-Naranjo, P Castellini, D Castro, F Castro Meira, A Cavallini, N Cayuela Caudevilla, S Cenciarelli, C Cereda, P Cerrone, A Chakrabarti, P Chaloulos-Iakovidis, A Chamorro, D Chandrasena, DI Chang, C Che, J Chembala, J Chen, Z Chen, T Chen, H Chen, X Chen, G Chen, L Chen, S Chen, B Cheripelli, M Chin, E Chiquete Anaya, M Chorazy, H Christensen, T Christensen, L Christian, F Chu, CS Chung, W Clark, R Clarke, S Claverie, E Clemente Agostoni, B Clissold, J Coelho, D Cohen, S Colakoglu, D Collas, R Condurso, SJ Connolly, D Consoli, C Constantin, AB Constantino Silva, L Contardo, A Corlobe, M Correia, C Correia, E Cortijo Garcia, B Coull, S Coutts, S Coveney, P Cras, R Crols, S Crozier, A Csanyi, L Csiba, K Csontos, R Csuha, L Cui, L Cunha, S Curtze, M Czerska, A Czlonkowska, M Czurko, M Czuryszkiewicz, M Dagnino, C Dai, A Daineko, G Dalek, D Damgaard, A Danese, K Dani, V Danku, W Dario Toledo, A Dávalos, A De Havenon, J De Keyser, N De Klippel, J De La Torre, A De Pauw, A De Smedt, R De Torres, MM De Vries Basson, J Dearborn, R Deganutto, M Degeorgia, I Deguchi, A Del Giudice, C Delcourt, R Delgado-Mederos, G Della Marca, B Delpont, S Deltour, DL Demets, M Dennis, J Desai, J Devine, I Dhollander, MT Di Mascio, M Diaconu, F Diaz Otero, J Dietzel, E Diez-Tejedor, N Ding, J Ding, M Diomedi, P Dioszeghy, M Distefano, V Domigo, E Dorodnicov, D Dossi, F Doubal, I Druzenko, P Du, J Du, T Duman, Y Duodu, D Dutta, L Dylewicz, J Eckstein, E Ehrensperger, S Ehrlich, G Einer Allende, B Elena Halac, S Elyas, M Endres, JM Engelbrecht, S Engelter, M Epinat, F Eren, M Esbjornsson, B Escribano, I Escudero, B Esisi, B Essa, M Esterbauer, N Evans, D Eveson, S Fabio, L Fang, S Fanta, M Fares, M Fatar, K Faust, A Favate, F Fazekas, M Federica Denaro, A Fedin, P Felipe Amaya, J Feng, K Ferencova, M Fernanda Gilli, MD Fernandez, PN Fernandez Pirrone, J Fernandez Vera, J Ferrari, A Ferreira, G Ferreira Junior, M Fidler, D Field, T Field, C Figueroa, J Fiksa, A Filipov, A Firstenfeld, L Fisch, U Fischer, M Fisselier, U Fiszer, F Fluri, G Fortea, K Fotherby, A Fraczek, E France, G Freitas, S Frey, M Frick, A Friedman, M Friedrich, G Frisullo, W Fryze, B Fuentes Gimeno, H Fujigasaki, K Fukuyama, A Furlan, G Furlanis, J Furnace, M Gabriel, E Gabriel Reich, RJ Gagliardi, F Galati, E Galli Giqueauk, A Gallina, E Gallinella, J Gallo, S Gangadharan, Y Gao, R Garcia Lopez, A Garcia Pastor, SM Garcia Sanchez, M Garnauf, P Garnier, D Gasecki, K Gasic, K Gasiorek, S Gasser, M Gaugg, M Gebreyohanns, K Gebura, J Geng, M Geniz Clavijo, K Georg Haeusler, R Geran, M Geremek, Z Gerocs, D Ghia, D Giannandrea, F Giatsidis, JA Gien Lopez, A Gil Nunez, L Gimenez, E Giralt, A Glabinski, D Gladstone, M Gliem, M Gluszkiewicz, R Goddeau, E Gogoleva, M Gokce, D Goldemund, K Golikov, A Gomes Neto, M Gomez Schneider, M Gomez-Choco, M Gomis, JF Gongora-Rivera, Y Gonysheva, L Gonzalez, ME Gonzalez Toledo, M Gottschal, I Gozdzik, S Grabowski, S Graf, D Green, D Greer, T Gregorio, S Greisenegger, I Greshnova, M Griebe, M Grzesik, J Guan, S Guarda, A Gueguen, C Guidoux, P Guillermo Povedano, B Guillon, V Guiraudg, G Gunathilagan, N Guryanova, V Gusev, G Gustavo Persi, R Gutiérrez, P Guyler, N Gyuker, V Hachinski, A Hajas, H Hallevi, G Hankey, GJ Hankey, L Hanouskova, L Hao, K Haraguchi, Y Haralur Sreekantaiah, S Haratz, D Hargroves, K Harkness, P Harmel, M Harrasser, RG Hart, M Harvey, R Hasan, Y Hasegawa, A Hassan, M Hattori, A Hatzitolios, M Hauk, T Hayashi, H Hayhoe, VS Hedna, M Heine, V Held, S Hellwig, J Henkner, N Henninger, S Hermans, J Hernandez, D Herrero, M Hervieu-Begue, R Herzig, L Hicken, M Hieber, M Hill, M Hirose, MC Hobeanu, B Hobson, M Hochstetter, J Hoe Heo, M Hoffmann, C Holmstedt, P Hon, KS Hong, Y Honma, A Horev, G Horgan, L Horvath, M Horvath, C Hoyer, D Huang, H Huang, B Huber, J Huhtakangas, M Hussain, S Igarashi, AM Iglesias Mohedano, J Ignacio Tembl, M Impellizzeri, Y Inanc, P Ioli, A Irina Aniculaesei, K Ishida, R Itabashi, H Iversen, A Jagolino, K Jakab, S Jander, H Janka, J Jankovych, J Jansen, L Jasek, M Javier Alet, L Javor, X Jin, P Jing, B Joachim, M Joan Macleod, M Johnson, J Jose Martin, C Joyner, K Judit Szabo, A Jun-Oconnell, R Jura, B Kaczorowska, J Kadlcikova, T Kahles, N Kakaletsis, I Kakuk, K Kalinowska, K Kaminska, C Kaneko, I Kanellos, P Kapeller, K Kapica-Topczewska, O Karasz, M Karlinski, JE Karlsson, K Kasa, E Kashaeva, SE Kasner, M Kaste, J Kasza, A Katalin Iljicsov, M Katsurayama, S Kaur, M Kawanishi, S Kaygorodtseva, K Ke, A Kei, J Keilitz, J Kellner, P Kelly, S Kelly, D Kemlink, M Kerekgyarto, I Keskinarkaus, D Khairutdinova, A Khanna, A Khaw, M Kholopov, C Khoumri, S Kirpicheva, H Kirshner, K Kitagawa, S Kittner, R Kivioja, F Klein, D Kleindorfer, T Kleinig, P Klivenyi, S Knecht, Y Kobayashi, A Kobayashi, M Koch, L Koehler, M Koivu, V Kolianov, I Koltsov, T Kondo, I Konkov, S Kopecky, E Korompoki, J Korpela, K Kosarz-Lanczek, A Koutroubi, K Kovacs, T Kovacs, H Kovacs, K Kowalczyk, M Kowalska, D Krajickova, M Kral, C Krarup Hansen, J Kraska, S Krebs, V Krejci, C Kremer, R Kreuzpointer, M Krzyzanowska, D Kucken, A Kulakowska, J Kunzmann, N Kurenkova, A Kuris, I Kurkowska-Jastrzebska, N Kurtenkova, O Kurushina, G Kusnick, M Kustova, T Kuwashiro, J Kwan Cha, A Lago, M Lagutenko, B Lajos, J Lambeck, C Lamy, A Landolfi, S Lanfranconi, W Lang, LB Lara Lezama, B Lara Rodriguez, T Largo, A Lasek-Bal, L Latte, V Lauer, P Lavados, R Le Bouc, R Leal Cantu, H Lechner, K Lecouturier, S Leder, J Lee, BC Lee, A Leger, E Leira, I Leisse, R Leker, G Lembo, L Lenskaya, J Leyden, G Li, M Li, S Li, J Li, G Liamis, H Liang, Z Liang, N Ligot, H Lin, R Lindert, A Lindgren, M Linna, T Litwin, K Liu, X Liu, L Llull, B Lohninger, M Longoni, C Loomis, D Lopes, M Lopez Fernandez, N Lopez Garza, A Lord, S Louw, R Lovasz, T Lowenkopf, Z Lu, SC Lubke-Detring, R Luder, S Lujan, B Luo, L Lupinogina, G Luschin, H Lutsep, A Lvova, J Ly, G.M. Grosse, H Ma, C Ma, M Machado, C Machado, S Macher, J Machetanz, F Macian-Montoro, E Mackey, A Mackey, G Maclean, J Maestre-Moreno, A Magadan, T Magyar, A Mahagney, A Majid, A Majjhoo, K Makaritsis, J Mandzia, M Mangas Guijarro, D Mangion, E Manios, S Mann, L Manning, C Manno, J Manuel Garcia, V Maqueda, M Mar Castellanos, M Mar Freijo, C Marando, S Marcela Lepera, J Marcos Couto, G Maria Bruera, L Maria Greco, A Maria Lorenzo, S Maria Obmann, A Maria Roa, C Marini, I Marinkovic, G Mario Sumay, C Mario Torres, M Marko, S Markova, H Markus, R Marsh, E Marsili, M Marta Esnaola, J Marta Moreno, J Marti-Fabregas, S Martina Angelocola, P Martínez Sánchez, N Martinez-Majander, S Martins, O Marzelik, S Mastrocola, G Matamala, A Matoltsy, B Matosevic, S Matsumoto, A Maud, G Mauri Cabdevila, Z May, Y Mayasi, A Mayr, T Mazzoli, K Mcarthur, L Mccullough, CE Medina Pech, F Medlin, M Mehdiratta, S Mehta, D Mehta, B Mehta, M Melis, E Melnikova, B Mendez, T Mendonca, JJ Mengual Chirifie, N Menon, A Mensch, E Meseguer, S Messe, K Metcalf, N Meyer, F Michas, N Micheletti, R Mikulik, H Milionis, B Miller, T Milling, C Minelli, J Minhas, M Minns, D Mircea, S Mishra, A Mismas, A Mistri, N Mitrovic, H Miyake, B Modrau, A Moey, C Molina, J Molina, A Molis, J Moller, S Molnar, F Moniche, C Monosi, V Monzani, M Moonis, R Morais, L Morales, A Morales, D Morar-Precup, F Moreton, C Moro, E Morozova, M Morton, T Morvan, E Morvan, T Motko, A Mowla, E Mozhejko, G Muddegowda, O Mudhar, T Mueller, C Muhl, KW Muir, H Mundl, S Munoz, C Murphy, S Murphy, A Murtuzova, T Musuka, J Mutzenbach, M Myint, W Mysliwy, M Naccarato, G Naeije, Y Nagakane, I Natarajan, D Navaratnam, A Nave, B Nazliel, K Nedeltchev, J Nel, H Nell, R Nemeth, L Nemeth, O Neto, K Ng, J Ngeh, L Nicolas Chialvo, T Nieminen, M Nikkanen, J Nikl, M Nikoforova, S Nishino, Y Nishiyama, X Njovane, S Nogawa, F Nombela, B Norrving, K Nosek, B Nowak, E Nowakowska-Sledz, G Ntaios, H Numminen, F Nunez, M Obadia, S Oberndorfer, A Obrezan, J Ochiai, W Oczkowski, MJ O'Donnell, A Odyniec, K Oh, M Ohira, Y Okamoto, M Okpala, S Okubo, L Olah, V Olavarria, J Oleszek, N Onat Demirci, V Ondar, G Ongun, K Ooyama, V Orosz, R Ortiz, G Osseby, E Österlund-Tauriala, C Ovesen, S Ozcekic Demirhan, J Ozdoba-Rot, S Ozturk, E Ozyurt, M Pablo Grecco, G Pablo Povedano, M Paciaroni, C Padiglioni, J Pagola, W Palasik, G Panczel, L Panos, G Papadopoulos, E Papadopoulou, A Papagiannis, V Papavasileiou, M Papina, JR Pardo De Donlebun, V Parisi, JM Park, J Pasten, N Patel, O Pavlik, M Pawelczyk, WF Peacock, H Pei, T Peisker, LF Pena Sedna, A Penn, S Pentek, E Pepper, L Pereira, K Perera, Y Perez, S Perez, P Perez Leguizamon, M Pernicka, R Perry, A Persico, Y Pesant, S Peska, D Peters, G Peters, L Pettigrew, T Phan, S Philippi, T Phinney, F Pico, A Pidal, B Piechowski-Jozwiak, A Pieroni, S Pineiro, V Piras, N Pizova, J Polanco, M Polin, A Polyakov, E Polychronopoulou, A Polymeris, D Popov, A Poppe, P Postorino, C Pozzerese, M Pradhan, L Prats, E Prazdnichkova, B Prendl, M Pretorius, P Profice, S Prokopenko, E Pudov, V Pujol Lereis, G Punzo Bravo, F Purroy, J Qiu, X Qu, V Quenardelle, H Quesada Garcia, L Radrizzani, A Radtke, T Raffelsberger, JM Ramirez Moreno, C Ramos-Estebanez, A Rani, P Rapantova, K Rashed, A Rasheed Nihara, J Rasmussen, L Redondo Robles, M Reif, P Reiner, P Rekova, A Renu, M Repetto, P Reyes, S Reyes Morales, JH Rha, J Ribeiro, S Ricci, C Richard, R Rigual, C Rinaldi, C Riveira Rodriguez, B Rizzato, TG Robinson, A Rocco, M Rodrigues, G Rodriguez, A Rodriguez Campello, F Rodriguez Lucci, M Rodriguez Yanez, C Roesler, C Roffe, R Roine, S Roine, A Roldan, F Romana Pezzella, M Romano, JS Roos, C Rosso, C Rostrup Kruuse, Y Roth, R Roukens, L Roveri, D Rozanski, J Rozniecki, C Rozsa, S Rudilosso, G Ruiz Ares, A Ruiz Franco, G Rum, J Ruuskanen, I Rybinnik, K Ryota, J Saarinen, V Saavedra, C Sabben, A Sabet, D Sagris, J Sahlas, N Sakai, P Salamanca, P Salgado, S Salig, T Salletmayr, M Salnikov, O Samoshkina, Y Samson, D Sanak, M Sànchez Cerón, P Santalucia, M Santamaria Cadavid, P Santiago, G Santo, B Sanz Cuesta, J Sargento, A Sarraj, K Sas, A Sas, O Satoshi, S Satsoglou, N Sattar, S Savitz, C Savopoulos, J Saw, M Sawicka, R Sawyer, T Scandura, N Schillinger, J Schindler, F Schlachetzki, I Schneider, R Schuppner, J Schurig, CJ Schwarzbach, M Sebejova, G Seidel, L Sekaran, D Selcuk, J Selvarajah, A Semerano, J Semjen, D Semushina, S Sen, M Seok Park, J Serena, O Serhat Tokgoz, W Serles, F Serrano, M Sevin, L Seynaeve, S Shah, N Shamalov, T Shang, M Sharma, A Sharrief, M Shazam Hussain, I Shchukin, W Shen, E Shepeleva, I Shinsuke, A Shmonin, A Shoamanesh, A Shuaib, A Shulga, G Sibolt, I Sibon, I Sicilia, M Siebert, E Sieczkowska, C Sila, AA Silva, D Silva, P Silva, Y Silva, M Silvestrini, Z Simony, A Simpkins, B Singh, D Sinha, I Sipos, O Skoda, P Skowron, M Skowronska, B Sliwinska, J Slonkova, A Smolkin, A Smyth, P Sobolewski, A Sobota, SI Sohn, M Soldatov, I Solganov, L Soloveva, E Solovyeva, N Sonntag, P Soors, M Sorgun, C Soriano, D Spence, K Spengos, L Sposato, G Staaf, K Stadler, L Stakhovskaya, K Stamatelopoulos, S Steinert, I Stetkarova, M Stiehm, R Stocker, J Stoinski, A Stoll, G Stotts, A Stumpp, P Sucapane, T Suenaga, X Sun, S Sundararajan, J Sung Kim, H Suzuki, N Svaneborg, G Szasz, W Szczuchniak, S Szczyrba, N Szegedi, A Szekely, Z Szewczyk, G Szilagyi, S Szlufik, K Szoboszlai, L Szpisjak, R Sztajzel, L Sztriha, SE Ta Wil, J Taggeselle, K Takamatsu, M Takao, W Taki, S Takizawa, M Talahma, A Tamayo, J Tan, D Tanne, A Tapanainen, T Tapiola, J Tarasiuk, T Tatlisumak, A Tayal, S Tcvetkova, P Teal, J Tejada Garcia, H Tejada Meza, D Tenora, M Terceno, A Terentiou, S Tezcan, D Thaler, A Thomson, E Thouvenot, M Tiainen, I Timberg, S Timsit, A Tinchon, D Tirschwell, C Togay Isikay, K Tokunaga, M Tolino, C Toloza, G Tomelleri, K Tomoyuki, LM Tomppo, Z Tong, L Tong, D Toni, J Torres, C Tossavainen, G Toth, A Tountopoulou, E Touze, M Tovar, K Toyoda, S Trillo, A Trommer, D Tropepi, D Tryambake, H Tu, S Tuetuencue, R Tumova, O Tumpula, G Turc, A Tutaj, J Tynkkynen, S Uchiyama, U Uchwat, L Uhrinyakova, R Ulku Acar, D Uluduz Ugurlu, X Urra, S Urui, M Usero Ruiz, D Vaclavik, K Vahedi, A Valikovics, J Valpas, P Van Acker, W Van Daele, G Vanderschueren, L Vanina Jure, R Varela, Z Varga, J Varvat, N Varvyanskaya, A Vasco Salgado, P Vasko, L Vass, S Vassilopoulou, I Vastagh, P Vazquez, L Vecsei, R Veltkamp, M Venti, M Verdugo, V Verocai, M Veronica Marroquin, C Veronica Simonsini, T Veverka, M Vigl, A Vila, C Vilar, JA Villanueva Osorio, J Virta, E Vitkova, B Voglsperger, J Volna, PA Von Weitzel-Mudersbach, N Vora, I Voznyuk, A Wach-Klink, A Wacongne, D Walters, Y Wang, J Wang, L Wang, X Wang, W Wang, N Wang, D Wang, H Wang, W Warnack, K Wartenberg, R Waters, M Waters, T Webb, J Weber, G Weiss, K Weissenborn, JI Weitz, B Weller, G Wen, G Weng, P Werner, D Werring, P Wester, W Whiteley, R Whiting, T Wijeratne, C Willems, L Wilson, C Wilson, T Winder, J Windt, A Winkler, A Winska-Tereszkiewicz, A Wisniewska, M Wittayer, A Wlodek, A Wojnarowska-Arendt, M Wolf, V Wolff, C Wolter, A Wong, H Wook Nah, H Worthmann, W Wu, S Wu, S Wunderlich, H Wurzinger, DG Wyse, B Xiao, W Xiaopeng, A Ximenez-Carrillo, L Xiong, Y Xiong, W Xiong, Y Xu, J Xu, Z Xu, B Yalo, T Yamada, M Yamasaki, L Yang, Y Yang, X Yang, Q Yang, B Yang, J Yang, I Yasuhiro, M Yee Lam, C Yegappan, S Yip, E Ylikallio, P Ylikotila, A Yongwon Jin, BW Yoon, Y Yoshida, L Yperzeele, H Yuan, H Yuasa, J Zalewska, C Zanferrari, E Zapata, D Zboznovits, I Zelenka, C Zhang, B Zhang, S Zhang, M Zhang, X Zhang, J Zhang, L Zhao, O Zhirnova, L Zhou, J Zielinska-Turek, I Zinchenko, M Ziomek, A Zitzmann, R Zweifler, J Zwiernik, Yperzeele, Laetitia, and NAVIGATE ESUS Investigators

Subjects
Male, International Cooperation, 030204 cardiovascular system & hematology, antiplatelet therapy, law.invention, Neurology (clinical), ischemic stroke, anticoagulation, Cohort Studies, 0302 clinical medicine, Randomized controlled trial, Rivaroxaban, law, Stroke, education.field_of_study, Aspirin, Anticoagulant, Settore BIO/14, Middle Aged, 3. Good health, Treatment Outcome, N/A, Cardiology, Platelet aggregation inhibitor, Settore MED/26 - Neurologia, Female, medicine.drug, medicine.medical_specialty, medicine.drug_class, MEDLINE, Population, Foramen Ovale, Patent, Subgroup analysis, Article, Statistics, Nonparametric, 03 medical and health sciences, Double-Blind Method, Internal medicine, medicine, Humans, education, Aged, business.industry, medicine.disease, Human medicine, business, 030217 neurology & neurosurgery, Platelet Aggregation Inhibitors, Factor Xa Inhibitors
Abstract

Background: \ud Patent foramen ovale (PFO) is a contributor to embolic stroke of undetermined source (ESUS). Subgroup analyses from previous studies suggest that anticoagulation could reduce recurrent stroke compared with antiplatelet therapy. We hypothesised that anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, would reduce the risk of recurrent ischaemic stroke compared with aspirin among patients with PFO enrolled in the NAVIGATE ESUS trial.\ud \ud Methods: \ud NAVIGATE ESUS was a double-blinded, randomised, phase 3 trial done at 459 centres in 31 countries that assessed the efficacy and safety of rivaroxaban versus aspirin for secondary stroke prevention in patients with ESUS. For this prespecified subgroup analysis, cohorts with and without PFO were defined on the basis of transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE). The primary efficacy outcome was time to recurrent ischaemic stroke between treatment groups. The primary safety outcome was major bleeding, according to the criteria of the International Society of Thrombosis and Haemostasis. The primary analyses were based on the intention-to-treat population. Additionally, we did a systematic review and random-effects meta-analysis of studies in which patients with cryptogenic stroke and PFO were randomly assigned to receive anticoagulant or antiplatelet therapy.\ud \ud Findings: \ud Between Dec 23, 2014, and Sept 20, 2017, 7213 participants were enrolled and assigned to receive rivaroxaban (n=3609) or aspirin (n=3604). Patients were followed up for a mean of 11 months because of early trial termination. PFO was reported as present in 534 (7·4%) patients on the basis of either TTE or TOE. Patients with PFO assigned to receive aspirin had a recurrent ischaemic stroke rate of 4·8 events per 100 person-years compared with 2·6 events per 100 person-years in those treated with rivaroxaban. Among patients with known PFO, there was insufficient evidence to support a difference in risk of recurrent ischaemic stroke between rivaroxaban and aspirin (hazard ratio [HR] 0·54; 95% CI 0·22–1·36), and the risk was similar for those without known PFO (1·06; 0·84–1·33; pinteraction=0·18). The risks of major bleeding with rivaroxaban versus aspirin were similar in patients with PFO detected (HR 2·05; 95% CI 0·51–8·18) and in those without PFO detected (HR 2·82; 95% CI 1·69–4·70; pinteraction=0·68). The random-effects meta-analysis combined data from NAVIGATE ESUS with data from two previous trials (PICSS and CLOSE) and yielded a summary odds ratio of 0·48 (95% CI 0·24–0·96; p=0·04) for ischaemic stroke in favour of anticoagulation, without evidence of heterogeneity.\ud \ud Interpretation: \ud Among patients with ESUS who have PFO, anticoagulation might reduce the risk of recurrent stroke by about half, although substantial imprecision remains. Dedicated trials of anticoagulation versus antiplatelet therapy or PFO closure, or both, are warranted.\ud \ud Funding: \ud Bayer and Janssen.

Published
2018

9. Practice patterns and outcomes after stroke across countries at different economic levels (INTERSTROKE): An international observational study

Author

Peter Langhorne, Martin J O'Donnell, Siu Lim Chin, Hongye Zhang, Denis Xavier, Alvaro Avezum, Nandini Mathur, Melanie Turner, Mary Joan MacLeod, Patricio Lopez-Jaramillo, Albertino Damasceno, Graeme J Hankey, Antonio L Dans, Ahmed Elsayed, Charles Mondo, Mohammad Wasay, Anna Czlonkowska, Christian Weimar, Afzal Hussein Yusufali, Fawaz Al Hussain, Liu Lisheng, Hans-Christoph Diener, Danuta Ryglewicz, Nana Pogosova, Romana Iqbal, Rafael Diaz, Khalid Yusoff, Aytekin Oguz, Xingyu Wang, Ernesto Penaherrera, Fernando Lanas, Okechukwu S Ogah, Adesola Ogunniyi, Helle K Iversen, German Malaga, Zvonko Rumboldt, Daliwonga Magazi, Yongchai Nilanont, Annika Rosengren, Shahram Oveisgharan, Salim Yusuf, M. O'Donnell, S. Yusuf, S. Rangarajan, P. Rao-Melacini, X. Michelle Zhang, S. Islam, C. Kabali, A. Casanova, S.L. Chin, J. DeJesus, M. Dehghan, S. Agapay, M. McQueen, K. Hall, J. Keys, X. Wang, A. Devanath, R. Gupta, D. Prabhakaran, R. Diaz, P. Schygiel, M. Garrote, M.A. Rodriguez, A. Caccavo, R.G. Duran, L. Sposato, J. Molinos, P. Valdez, C.M. Cedrolla, P.G. Nofal, M.F. Huerta, P.M. Desmery, M.C. Zurru, B. Della Vedova, J. Varigos, G. Hankey, T. Kraemer, P. Gates, C. Bladin, G. Herkes, A. Avezum, M.P. Pereira, L. Minuzzo, L. Oliveira, M. Teixeira, H. Reis, A. Carvalho, S. Ouriques Martins, J.J. Carvalho, O. Gebara, C. Minelli, D.C. Oliveira, A.C. Sobral Sousa, A.C. Ferraz de Almeida, M.E. Hernandez, M. Friedrich, D.M. Mota, L.E. Ritt, D. Correa Vila Nova, P. Teal, D. Gladstone, A. Shuaib, F. Silver, D. Dowlatshahi, F. Lanas, D. Carcamo, C. Santibañez, E. Garces, L.S. Liu, H.Y. Zhang, H.P. Fang, M.F. Lian, F. Shen, F.X. Luo, X.X. Wen, Z.Q. Xu, Z.Z. Liu, W. Yan, J.F. Yu, W.K. Wang, L.H. Liu, Y.H. Sun, L.C. Zhou, Z.F. Zhang, J. LV, C.S. Zhang, G. Chen, H.L. Wang, Y. Chen, H. Zheng, J.J. Huang, W.Z. Li, L.J. Wang, J.X. Shi, C.Y. Hu, H.F. Song, R.Y. Ji, D.L. Wang, L.H. Meng, Q.W. Meng, L.J. Duan, H.F. Liu, Y.C. Luo, Q.Y. Zhang, Y.B. Wu, C.R. Wang, J.G. Zhao, S.G. Liu, C.L. Shi, X.Y. Wang, P. Lopez-Jaramillo, A. Martinez, G. Sanchez-Vallejo, D.I. Molina, T. Espinosa, H. Garcia Lozada, D. Gomez-Arbelaez, P.A. Camacho, Z. Rumboldt, I. Lusic, H.K. Iversen, T. Truelsen, C. Back, M.M. Pedersen, E. Peñaherrera, Y.C. Duarte, S. Cevallos, D. Tettamanti, S. Caceres, H.C. Diener, C. Weimar, A. Grau, J. Rother, M. Ritter, T. Back, Y. Winter, P. Pais, D. Xavier, A. Sigamani, N. Mathur, P. Rahul, A. Murali, A.K. Roy, G.R.K. Sarma, T. Matthew, G. Kusumkar, K.A. Salam, U. Karadan, L. Achambat, Y. Singh, J.D. Pandian, R. Verma, V. Atam, A. Agarwal, N. Chidambaram, R. Umarani, S. Ghanta, G.K. Babu, G. Sathyanarayana, G. Sarada, S. Navya Vani, R. Sundararajan, S.S. Sivakumar, R.S. Wadia, S. Bandishti, R.R. Agarwal, I. Mohan, S. Joshi, S. Kulkarni, S. Partha Saradhi, P. Joshi, M. Pandharipande, N. Badnerkar, R. Joshi, S.P. Kalantri, S. Somkumar, S. Chauhan, H. Singh, S. Varma, G.K. Sidhu, R. Singh, K.L. Bansal, A. Bharani, S. Pagare, A. Chouhan, B.N. Mahanta, T.G. Mahanta, G. Rajkonwar, S.K. Diwan, S.N. Mahajan, P. Shaikh, H.R. Devendrappa, B.K. Agrawal, A. Agrawal, D. Khurana, S. Thakur, V. Jain, S. Oveisgharan, A. Bahonar, R. Kelishadi, A. Hossienzadeh, M. Raeisidehkordi, H. Akhavan, T. Walsh, O. Albaker, K. Yusoff, A. Chandramouli, S. Shahadan, Z. Ibrahim, A. Husin, A. Damasceno, V. Lobo, S. Loureiro, V.A. Govo, O.S. Ogah, A. Ogunniyi, R.O. Akinyemi, M.O. Owolabi, M.U. Sani, L.F. Owolabi, R. Iqbal, M. Wasay, A. Raza, G.G. Malaga, M. Lazo-Porras, J.D. Loza-Herrera, A. Acuña-Villaorduña, D. Cardenas-Montero, A. Dans, E. Collantes, D. Morales, A. Roxas, M.V.C. Villarruz-Sulit, A. Czlonkowska, D. Ryglewicz, M. Skowronska, M. Restel, A. Bochynska, K. Chwojnicki, M. Kubach, A. Stowik, M. Wnuk, N. Pogosova, A. Ausheva, A. Karpova, V. Pshenichnikova, A. Vertkin, A. Kursakov, S. Boytsov, F. Al-Hussain, L. DeVilliers, D. Magazi, B. Mayosi, A.S.A. Elsayed, A. Bikhari, Z. Sawaraldahab, H. Hamad, M. ElTaher, A. Abdelhameed, M. Alawad, D. Alkabashi, H. Alsir, A. Rosengren, M. Andreasson, J. Kembro Johansson, B. Cederin, C. Schander, A.C. Elgasen, E. Bertholds, K. Boström Bengtsson, Y. Nilanont, S. Nidhinandana, P. Tatsanavivat, N. Paryoonwiwat, N. Poungvarin, N.C. Suwanwela, S. Tiamkao, R. Tulyapornchote, S. Boonyakarnkul, S. Hanchaiphiboolkul, S. Muengtaweepongsa, K. Watcharasaksilp, P. Sathirapanya, P. Pleumpanupat, A. Oguz, A.A. Akalin, O.T. Caklili, N. Isik, B. Caliskan, B. Sanlisoy, E. Balkuv, H. Tireli, V. Yayla, M. Cabalar, A. Culha, S. Senadim, B. Arpaci, C. Dayan, T. Argun, S. Yilmaz, S. Celiker, A. Kocer, T. Asil, G. Eryigit, C. Mondo, J. Kayima, M. Nakisige, S. Kitoleeko, A.M. Yusufali, B.J. Zuberi, H.Z. Mirza, A.A. Saleh, J.M. BinAdi, F. Hussain, P. Langhorne, K. Muir, M. Walters, C. McAlpine, S. Ghosh, A. Doney, S. Johnston, P. Mudd, T. Black, P. Murphy, D. Jenkinson, D. Kelly, R. Whiting, D. Dutta, L. Shaw, C. Mcfarlane, E. Ronald, and K. McBurnie

Subjects
Male, medicine.medical_specialty, MEDLINE, Medizin, Developing country, 030204 cardiovascular system & hematology, Health Services Accessibility, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, medicine, Humans, Practice Patterns, Physicians', Stroke, Developing Countries, Poverty, Aged, Evidence-Based Medicine, business.industry, Developed Countries, Case-control study, General Medicine, Evidence-based medicine, Middle Aged, medicine.disease, Survival Analysis, purl.org/pe-repo/ocde/ford#3.02.00 [https], Patient Outcome Assessment, Treatment Outcome, Family medicine, Case-Control Studies, Observational study, Female, Interstroke, business, Developed country, 030217 neurology & neurosurgery
Abstract

9 p., Background: Stroke disproportionately affects people in low-income and middle-income countries. Although improvements in stroke care and outcomes have been reported in high-income countries, little is known about practice and outcomes in low and middle-income countries. We aimed to compare patterns of care available and their association with patient outcomes across countries at different economic levels. Methods: We studied the patterns and effect of practice variations (ie, treatments used and access to services) among participants in the INTERSTROKE study, an international observational study that enrolled 13 447 stroke patients from 142 clinical sites in 32 countries between Jan 11, 2007, and Aug 8, 2015. We supplemented patient data with a questionnaire about health-care and stroke service facilities at all participating hospitals. Using univariate and multivariate regression analyses to account for patient casemix and service clustering, we estimated the association between services available, treatments given, and patient outcomes (death or dependency) at 1 month. Findings: We obtained full information for 12 342 (92%) of 13 447 INTERSTROKE patients, from 108 hospitals in 28 countries; 2576 from 38 hospitals in ten high-income countries and 9766 from 70 hospitals in 18 low and middle-income countries. Patients in low-income and middle-income countries more often had severe strokes, intracerebral haemorrhage, poorer access to services, and used fewer investigations and treatments (p

Published
2018

10. Family-led rehabilitation after stroke in India (ATTEND): a randomised controlled trial

Author

R I Lindley, C S Anderson, L Billot, A Forster, M L Hackett, L A Harvey, S Jan, Q Li, H Liu, P Langhorne, P K Maulik, G V S Murthy, M F Walker, J D Pandian, M Alim, C Felix, A Syrigapu, D K Tugnawat, S J Verma, B R Shamanna, G Hankey, A Thrift, J Bernhardt, M M Mehndiratta, L Jeyaseelan, P Donnelly, D Byrne, S Steley, V Santhosh, S Chilappagari, J Mysore, J Roy, M V Padma, L John, S Aaron, N C Borah, P Vijaya, S Kaul, D Khurana, P N Sylaja, D S Halprashanth, B K Madhusudhan, V Nambiar, S Sureshbabu, M C Khanna, G S Narang, D Chakraborty, S S Chakraborty, B Biswas, S Kaura, H Koundal, P Singh, A Andrias, D S Thambu, I Ramya, J George, A T Prabhakar, P Kirubakaran, P Anbalagan, M Ghose, K Bordoloi, P Gohain, N M Reddy, K V Reddy, T N M Rao, S Alladi, V R R Jalapu, K Manchireddy, A Rajan, S Mehta, C Katoch, B Das, A Jangir, T Kaur, S Sreedharan, S Sivasambath, S Dinesh, B S Shibi, A Thangaraj, A Karunanithi, S M S Sulaiman, K Dehingia, K Das, C Nandini, N J Thomas, T S Dhanya, N Thomas, R Krishna, V Aneesh, S Khullar, S Thouman, and I Sebastian

Subjects
Adult, Male, medicine.medical_specialty, Activities of daily living, Adolescent, medicine.medical_treatment, India, Home Care Services, Hospital-Based, law.invention, 03 medical and health sciences, Disability Evaluation, Young Adult, 0302 clinical medicine, Randomized controlled trial, law, Modified Rankin Scale, Activities of Daily Living, medicine, Humans, Family, Single-Blind Method, 030212 general & internal medicine, Prospective Studies, Stroke, Aged, Aged, 80 and over, Rehabilitation, Intention-to-treat analysis, Family caregivers, business.industry, Stroke Rehabilitation, General Medicine, Middle Aged, medicine.disease, Clinical trial, Caregivers, Socioeconomic Factors, Physical therapy, Quality of Life, Educational Status, Female, business, 030217 neurology & neurosurgery
Abstract

Background: \ud \ud Most people with stroke in India have no access to organised rehabilitation services. The effectiveness of training family members to provide stroke rehabilitation is uncertain. Our primary objective was to determine whether family-led stroke rehabilitation, initiated in hospital and continued at home, would be superior to usual care in a low-resource setting.\ud \ud Methods: \ud \ud The Family-led Rehabilitation after Stroke in India (ATTEND) trial was a prospectively randomised open trial with blinded endpoint done across 14 hospitals in India. Patients aged 18 years or older who had had a stroke within the past month, had residual disability and reasonable expectation of survival, and who had an informal family-nominated caregiver were randomly assigned to intervention or usual care by site coordinators using a secure web-based system with minimisation by site and stroke severity. The family members of participants in the intervention group received additional structured rehabilitation training—including information provision, joint goal setting, carer training, and task-specific training—that was started in hospital and continued at home for up to 2 months. The primary outcome was death or dependency at 6 months, defined by scores 3–6 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) as assessed by masked observers. Analyses were by intention to treat. This trial is registered with Clinical Trials Registry-India (CTRI/2013/04/003557), Australian New Zealand Clinical Trials Registry (ACTRN12613000078752), and Universal Trial Number (U1111-1138-6707).\ud \ud Findings: \ud \ud Between Jan 13, 2014, and Feb 12, 2016, 1250 patients were randomly assigned to intervention (n=623) or control (n=627) groups. 33 patients were lost to follow-up (14 intervention, 19 control) and five patients withdrew (two intervention, three control). At 6 months, 285 (47%) of 607 patients in the intervention group and 287 (47%) of 605 controls were dead or dependent (odds ratio 0·98, 95% CI 0·78–1·23, p=0·87). 72 (12%) patients in the intervention group and 86 (14%) in the control group died (p=0·27), and we observed no difference in rehospitalisation (89 [14%]patients in the intervention group vs 82 [13%] in the control group; p=0·56). We also found no difference in total non-fatal events (112 events in 82 [13%] intervention patients vs 110 events in 79 [13%] control patients; p=0·80).\ud Interpretation: \ud \ud Although task shifting is an attractive solution for health-care sustainability, our results do not support investment in new stroke rehabilitation services that shift tasks to family caregivers, unless new evidence emerges. A future avenue of research should be to investigate the effects of task shifting to health-care assistants or team-based community care.\ud \ud Funding: \ud \ud The National Health and Medical Research Council of Australia.

Published
2017

11. A non-human primate model of radiation-induced cachexia

Author

Alexander Bennett, Pei Zhang, Cassandra P. Smith, Sean R. Kearney, Wanchang Cui, Thomas J. MacVittie, Kim G. Hankey, Kory R. Barrow, Allison Gibbs, and Cheryl Taylor-Howell

Subjects
0301 basic medicine, Male, medicine.medical_specialty, Cachexia, Time Factors, medicine.medical_treatment, Activin Receptors, Type II, Inflammation, Myostatin, Article, 03 medical and health sciences, Hemoglobins, 0302 clinical medicine, Weight loss, Internal medicine, Weight Loss, medicine, Animals, Humans, Muscle, Skeletal, Wasting, Serum Albumin, Retrospective Studies, Multidisciplinary, SKP Cullin F-Box Protein Ligases, biology, business.industry, Skeletal muscle, Dose-Response Relationship, Radiation, medicine.disease, Macaca mulatta, humanities, Radiation therapy, Dose–response relationship, Disease Models, Animal, Muscular Atrophy, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, Gene Expression Regulation, Gamma Rays, 030220 oncology & carcinogenesis, biology.protein, medicine.symptom, business
Abstract

Cachexia, or muscle wasting, is a serious health threat to victims of radiological accidents or patients receiving radiotherapy. Here, we propose a non-human primate (NHP) radiation-induced cachexia model based on clinical and molecular pathology findings. NHP exposed to potentially lethal partial-body irradiation developed symptoms of cachexia such as body weight loss in a time- and dose-dependent manner. Severe body weight loss as high as 20–25% was observed which was refractory to nutritional intervention. Radiographic imaging indicated that cachectic NHP lost as much as 50% of skeletal muscle. Histological analysis of muscle tissues showed abnormalities such as presence of central nuclei, inflammation, fatty replacement of skeletal muscle and muscle fiber degeneration. Biochemical parameters such as hemoglobin and albumin levels decreased after radiation exposure. Levels of FBXO32 (Atrogin-1), ActRIIB and myostatin were significantly changed in the irradiated cachectic NHP compared to the non-irradiated NHP. Our data suggest NHP that have been exposed to high dose radiation manifest cachexia-like symptoms in a time- and dose-dependent manner. This model provides a unique opportunity to study the mechanism of radiation-induced cachexia and will aid in efficacy studies of mitigators of this disease.

Published
2016

12. Estimated GFR and the Effect of Intensive Blood Pressure Lowering After Acute Intracerebral Hemorrhage

Author

Danni Zheng, Shoichiro Sato, Hisatomi Arima, Emma Heeley, Candice Delcourt, Yongjun Cao, John Chalmers, Craig S. Anderson, C.S. Anderson, J. Chalmers, H. Arima, S. Davis, E. Heeley, Y. Huang, P. Lavados, B. Neal, M.W. Parsons, R. Lindley, L. Morgenstern, T. Robinson, C. Stapf, C. Tzourio, J.G. Wang, S. Chen, X.Y. Chen, L. Cui, Z. Liu, C. Lu, J. Wang, S. Wu, E. Xu, Q. Yang, C. Zhang, J. Zhang, R. Beer, E. Schmutzhard, P. Redondo, M. Kaste, L. Soinne, T. Tatlisumak, K. Wartenberg, S. Ricci, K. Klijn, E. Azevedo, A. Chamorro, M. Arnold, U. Fischer, S. Kaul, J. Pandian, H. Boyini, S. Singh, A.A. Rabinstein, C. Estol, G. Silva, V.V. Olavarria, T.G. Robinson, R.J. Simes, M.-G. Bousser, G. Hankey, K. Jamrozik, S.C. Johnston, S. Li, K. Bailey, T. Cheung, C. Delcourt, S. Chintapatla, E. Ducasse, T. Erho, J. Hata, B. Holder, E. Knight, M. Leroux, T. Sassé, E. Odgers, R. Walsh, Z. Wolfowicz, G. Chen, S. Fuentes, B. Peng, H.-M. Schneble, M.-X. Wang, L. Billot, S. Heritier, Q. Li, M. Woodward, S. Abimbola, S. Anderson, E. Chan, G. Cheng, P. Chmielnik, S. Leighton, J.-Y. Liu, B. Rasmussen, A. Saxena, S. Tripathy, M. Armenis, M.A. Baig, B. Naidu, G. Starzec, S. Steley, A. Moles, A. Ruiz, M. Zimmermann, J. Marinho, S. Alves, R. Angelim, J. Araujo, L. Kawakami, C. Bustos, F. Gonzalez, P. Munoz Venturelli, X. Chen, R. Jia, N. Li, S. Qu, Y. Shu, A. Song, J. Sun, J. Xiao, Y. Zhao, Q. Huang, E. Vicaut, A. Chamam, M.-C. Viaud, C. Dert, U. Fiedler, V. Jovis, S. Kabla, S. Marchand, A. Pena, V. Rochaud, K. Mallikarjuna, N. Hasan, E. Berge, E.C. Sandset, A.S. Forårsveen, D. Richardson, T. Kumar, S. Lewin, N. Poulter, J. Field, A. Anjum, A. Wilson, H. Perelmuter, A.M. Agarie, A.G. Barboza, L.A. Recchia, I.F. Miranda, S.G. Rauek, R.J. Duplessis, H. Dewey, L. Walker, S. Petrolo, C. Bladin, J. Sturm, D. Crimmins, D. Griffiths, A. Schutz, V. Zenteno, F. Miteff, N. Spratt, E. Kerr, C.R. Levi, T.G. Phan, H. Ma, L. Sanders, C. Moran, K. Wong, S. Read, R. Henderson, A. Wong, R. Hull, G. Skinner, P. Hand, B. Yan, H. Tu, B. Campbell, D.J. Blacker, T. Wijeratne, M. Pathirage, M. Jasinararchchi, Z. Matkovic, S. Celestino, F. Gruber, M.R. Vosko, E. Diabl, S. Rathmaier, B. Pfausler, R. Helbok, F. Fazekas, R. Fischer, B. Poltrum, B. Zechner, U. Trummer, M.P. Rutgers, A. Peeters, A. Dusart, M.-C. Duray, C. Parmentier, S. Ferrao-Santos, R. Brouns, S. De Raedt, A. De Smedt, R.-J. VanHooff, J. De Keyser, S.C.O. Martins, A.G. de Almeida, R. Broudani, N.F. Titton, G.R. de Freitas, F.M. Cardoso, L.M. Giesel, N.A. Lima, A.C. Ferraz de Almeida, R.B. Gomes, T.S. Borges dos Santos, E.M. Veloso Soares, O.L.A. Neto, G.S. Silva, D.L. Gomes, F.A. de Carvalho, M. Miranda, A. Marques, V.F. Zétola, G. de Matia, M.C. Lange, J. Montes, A. Reccius, A. Soto, R. Rivas, C. Klapp, S. Illanes, C. Aguilera, A. Castro, C. Figueroa, J. Benavides, P. Salamanca, M.C. Concha, J. Pajarito, P. Araya, F. Guerra, Y. Li, G. Liu, B. Wang, Y. Chong, M. He, L. Wang, J. Liu, X. Zhang, C. Lai, H. Jiang, S. Cui, Q. Tao, Y. Zhang, S. Yao, M. Xu, H. Xiao, J. Hu, J. Tang, H. Ji, M. Jiang, F. Yu, X. Yang, X. Guo, Y. Wang, L. Wu, Y. Gao, D. Sun, X. Huang, L. Liu, P. Li, Y. Jiang, H. Li, H. Lu, J. Zhou, C. Yuan, X. Qi, F. Qiu, H. Qian, W. Wang, W. Sun, F. Li, R. Liu, Q. Peng, Z. Ren, C. Fan, H. Wang, T. Wang, F. Shi, C. Duan, Z. Chen, X. Tan, Z. Zhao, J. Chen, T. Han, L. Zhang, Q. Hu, Q. Hou, X. Zhao, G. Zeng, L. Ma, F. Wang, L. Zeng, Z. Guo, Y. Fu, Y. Song, L. Tai, X. Liu, X. Su, Y. Yang, R. Dong, Y. Xu, S. Tian, S. Cheng, L. Su, X. Xie, T. Xu, D. Geng, X. Yan, H. Fan, N. Zhao, S. Wang, J. Yang, M. Yan, L. Li, Z. Li, X. Xu, Y. Lian, H. Sun, D. Liu, N. Wang, Q. Tang, Z. Han, L. Feng, Y. Cui, J. Tian, H. Chang, X. Sun, C. Liu, Z. Wen, Q. Lin, L. Sun, B. Hu, M. Zou, Q. Bao, X. Lin, L. Zhao, X. Tian, X. Wang, X. Li, L. Hao, Y. Duan, R. Wang, Z. Wei, S. Ren, H. Ren, Y. Dong, Y. Cheng, W. Liu, J. Han, Z. Zhang, J. Zhu, J. Qian, Y. Sun, K. Liu, F. Long, X. Peng, Q. Zhang, Z. Yuan, C. Wang, M. Huang, P. He, Y. You, J. Xia, L. Zhou, Y. Hou, Y. Qi, L. Mei, R. Lu, L. Ping, S. Zhou, S. Zhang, R. Zou, J. Guo, M. Li, W. Wei, S. Curtze, M. Saarela, D. Strbian, F. Scheperjans, T. De Broucker, C. Henry, R. Cumurciuc, N. Ibos-Augé, A.-C. Zéghoudi, F. Pico, O. Dereeper, M.-C. Simian, C. Boisselier, A. Mahfoud, S. Timsit, F.M. Merrien, B. Guillon, M. Sevin, F. Herisson, C. Magne, A. Ameri, C. Cret, S. Stefanizzi, F. Klapzcynski, C. Denier, M. Sarov-Riviere, P. Reiner, J. Mawet, D. Hervé, F. Buffon, E. Touzé, V. Domigo, C. Lamy, D. Calvet, M. Pasquini, S. Alamowitch, P. Favrole, I.-P. Muresan, S. Crozier, C. Rosso, C. Pires, A. Leger, S. Deltour, C. Cordonnier, H. Henon, C. Rossi, M. Zuber, M. Bruandet, R. Tamazyan, C. Join-Lambert, E. Juettler, T. Krause, S. Maul, M. Endres, G.J. Jungehulsing, M. Hennerici, M. Griebe, T. Sauer, K. Knoll, R. Huber, K. Knauer, C. Knauer, S. Raubold, H. Schneider, H. Hentschel, C. Lautenschläger, E. Schimmel, I. Dzialowski, C. Foerch, M. Lorenz, O. Singer, I.M.R. Meyer dos Santos, A. Hartmann, A. Hamann, A. Schacht, B. Schrader, A. Teíchmann, K.E. Wartenberg, T.J. Mueller, S. Jander, M. Gliem, C. Boettcher, M. Rosenkranz, C. Beck, D. Otto, G. Thomalla, B. Cheng, K.S. Wong, T.W. Leung, Y.O.Y. Soo, S. Prabhakar, S.R. Kesavarapu, P.K. Gajjela, R.R. Chenna, K. Ummer, M. Basheer, A. Andipet, M.K.M. Jagarlapudi, A.U.R. Mohammed, V.G. Pawar, S.S.K. Eranki, Y. Singh, N. Akhtar, N.C. Borah, M. Ghose, N. Choudhury, N.R. Ichaporia, J. Shendge, S. Khese, V. Pamidimukkala, P. Inbamuthaiah, S.R. Nuthakki, N.M.R. Tagallamudi, A.K. Gutti, D. Khurana, P. Kesavarapu, V. Jogi, A. Garg, D. Samanta, G.R.K. Sarma, R. Nadig, T. Mathew, M.A. Anandan, E. Caterbi, A. Zini, M. Cavazzuti, F. Casoni, R. Pentore, F. Falzone, T. Mazzoli, L.M. Greco, C. Menichetti, F. Coppola, S. Cenciarelli, E. Gallinella, A. Mattioni, R. Condurso, I. Sicilia, M. Zampolini, F. Corea, M. Barbi, C. Proietti, D. Toni, A. Pieroni, A. Anzini, A. Falcou, M. Demichele, C.J.M. Klijn, A. Tveiten, E.T. Thortveit, S. Pettersen, N. Holand, B. Hitland, S.H. Johnsen, A. Eltoft, M. Wasay, A. Kamal, A. Iqrar, L. Ali, D. Begum, G. Gama, L. Fonseca, G. Moreira, L.M. Veloso, D. Pinheiro, L. Paredes, C. Rozeira, T. Gregorio, T. Segura Martin, O. Ayo, J. Garcia-Garcia, I. Feria Vilar, I. Gómez Fernández, S. Amaro, X. Urra, V. Obach, A. Cervera, Y. Silva, J. Serena, M. Castellanos, M. Terceno, C. Van Eendenburg, A. Weck, O. Findling, R. Lüdi, E.A. Warburton, D. Day, N. Butler, E. Bumanlag, S. Caine, A. Steele, M. Osborn, E. Dodd, P. Murphy, B. Esisi, E. Brown, R. Hayman, V.K.V. Baliga, M. Minphone, J. Kennedy, I. Reckless, G. Pope, R. Teal, K. Michael, D. Manawadu, L. Kalra, R. Lewis, B. Mistry, E. Cattermole, A. Hassan, L. Mandizvidza, J. Bamford, H. Brooks, C. Bedford, R. Whiting, P. Baines, M. Hussain, M. Harvey, K. Fotherby, S. McBride, P. Bourke, D. Morgan, K. Jennings-Preece, C. Price, S. Huntley, V.E. Riddell, G. Storey, R.L. Lakey, G. Subramanian, D. Jenkinson, J. Kwan, O. David, D. Tiwari, M. James, S. Keenan, H. Eastwood, L. Shaw, P. Kaye, D. Button, B. Madigan, D. Williamson, A. Dixit, J. Davis, M.O. Hossain, G.A. Ford, A. Parry-Jones, V. O'Loughlin, R. Jarapa, Z. Naing, C. Lovelock, J. O'Reilly, U. Khan, A. Bhalla, A. Rudd, J. Birns, D.J. Werring, R. Law, R. Perry, I. Jones, R. Erande, C. Roffe, I. Natarajan, N. Ahmad, K. Finney, J. Lucas, A. Mistri, D. Eveson, R. Marsh, V. Haunton, J.E. Fugate, S.W. Lepore, Neurologian yksikkö, Clinicum, Neurology, Clinical sciences, Neuroprotection & Neuromodulation, Supporting clinical sciences, UZB Other, Physical Medicine and Rehabilitation, and Vriendenkring VUB

Subjects
CHRONIC KIDNEY-DISEASE, Male, systolic blood pressure, medicine.medical_treatment, Blood Pressure, 030204 cardiovascular system & hematology, GLOMERULAR-FILTRATION-RATE, 3124 Neurology and psychiatry, RESISTANT HYPERTENSION, 0302 clinical medicine, Modified Rankin Scale, cerebral hemorrhage, cerebrovascular disease, chronic kidney disease (CKD), dialysis, estimated glomerular filtration rate (EGFR), hemodialysis, intensive blood pressure lowering treatment, INTERACT2, intracerebral hemorrhage (ICH), Kidney function, stroke, Stroke, education.field_of_study, OUTCOMES, estimated glomerular filtration rate (eGFR), Antihypertensive Agents/pharmacology, ASSOCIATION, Urology & Nephrology, Middle Aged, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], 3. Good health, PREVALENCE, Nephrology, Acute Disease, Female, Cerebral Hemorrhage/drug therapy, WHITE-MATTER, Glomerular Filtration Rate, STROKE PATIENTS, medicine.medical_specialty, RENAL-FUNCTION, LONG-TERM, Population, Renal function, Blood Pressure/drug effects, 03 medical and health sciences, Internal medicine, medicine, Humans, education, Dialysis, Antihypertensive Agents, Aged, Cerebral Hemorrhage, Intracerebral hemorrhage, business.industry, 1103 Clinical Sciences, medicine.disease, Surgery, Blood pressure, business, 030217 neurology & neurosurgery, Kidney disease
Abstract

Markku Kaste ja Filip Scheperjans työryhmän jäsenenä. Background: The kidney-brain interaction has been a topic of growing interest. Past studies of the effect of kidney function on intracerebral hemorrhage (ICH) outcomes have yielded inconsistent findings. Although the second, main phase of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2) suggests the effectiveness of early intensive blood pressure (BP) lowering in improving functional recovery after ICH, the balance of potential benefits and harms of this treatment in those with decreased kidney function remains uncertain. Study Design: Secondary analysis of INTERACT2, which randomly assigned patients with ICH with elevated systolic BP (SBP) to intensive (target SBP 90, 60-90, and Outcomes: The effect of admission eGFR on the primary outcome of death or major disability at 90 days (defined as modified Rankin Scale scores of 3-6) was analyzed using a multivariable logistic regression model. Potential effect modification of intensive BP lowering treatment by admission eGFR was assessed by interaction terms. Results: Of 2,623 included participants, 912 (35%) and 280 (11%) had mildly and moderately/severely decreased eGFRs, respectively. Patients with moderately/severely decreased eGFRs had the greatest risk for death or major disability at 90 days (adjusted OR, 1.82; 95% CI, 1.28-2.61). Effects of early intensive BP lowering were consistent across different eGFRs (P = 0.5 for homogeneity). Limitations: Generalizability issues arising from a clinical trial population. Conclusions: Decreased eGFR predicts poor outcome in acute ICH. Early intensive BP lowering provides similar treatment effects in patients with ICH with decreased eGFRs. Am J Kidney Dis. 68(1): 94-102. (C) 2016 The Authors. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is an open access article under the CC BY-NC-ND license.

Published
2015

13. Detection of CD4+T-cell antibodies in a patient with idiopathic CD4+T lymphocytopenia and cryptococcal meningitis

Author

Dean L. Mann, Rosemary Yi, Kim G. Hankey, Aaron P. Rapoport, and Rachel B. Salit

Subjects
CD4-Positive T-Lymphocytes, Male, Meningitis, Cryptococcal, Immunoglobulin E, Peripheral blood mononuclear cell, medicine, Humans, Psoriasis, T-Lymphocytopenia, Idiopathic CD4-Positive, Aged, Autoantibodies, Leukopenia, biology, business.industry, Antibodies, Monoclonal, Hematology, T lymphocyte, Flow Cytometry, medicine.disease, CD4 Lymphocyte Count, Immunoglobulin G, Immunology, biology.protein, medicine.symptom, Lymphocytopenia, Antibody, business, Meningitis, Monoclonal gammopathy of undetermined significance
Abstract

Summary Idiopathic CD4 + T lymphocytopenia (ICL) is defined as a CD4 + T-cell count

Published
2007

14. National stroke association guidelines for the management of transient ischemic attacks

Author

S. C. Johnston, Louis R. Caplan, Robert G. Hart, Miriam E. Schwarz, Christina E Williams, Kate Fuller, Ralph L. Sacco, A. Algra, G. Hankey, S.A. Josephson, Ronald D. Brown, Peter J. Koudstaal, Steven R. Levine, Mai N. Nguyen-Huynh, Gregory W. Albers, Harold P. Adams, José Biller, Julien Bogousslavsky, J. van Gijn, L.J. Kappelle, Peter M. Rothwell, Neurology, and Cardiology

Subjects
medicine.medical_specialty, Health Planning Guidelines, media_common.quotation_subject, MEDLINE, Internal medicine, medicine, Humans, Quality (business), Transient (computer programming), Association (psychology), Stroke, media_common, business.industry, Conflict of interest, Evidence-based medicine, medicine.disease, United States, Surgery, Ophthalmology, Review Literature as Topic, Systematic review, Neurology, Ischemic Attack, Transient, Cardiology, Neurology (clinical), Medical emergency, business
Abstract

Objective: Transient ischemic attacks are common and important harbingers of subsequent stroke. Management varies widely, and most published guidelines have not been updated in several years. We sought to create comprehensive, unbiased, evidence-based guidelines for the management of patients with transient ischemic attacks. Methods: Fifteen expert panelists were selected based on objective criteria, using publication metrics that predicted nomination by practitioners in the field. Prior published guidelines were identified through systematic review, and recommendations derived from them were rated independently for quality by the experts. Highest quality recommendations were selected and subsequently edited by the panelists using a modified Delphi approach with multiple iterations of questionnaires to reach consensus on new changes. Experts were provided systematic reviews of recent clinical studies and were asked to justify wording changes based on new evidence and to rate the final recommendations based on level of evidence and quality. No expert was allowed to contribute to recommendations on a topic for which there could be any perception of a conflict of interest. Results: Of 257 guidelines documents identified by systematic review, 13 documents containing 137 recommendations met all entry criteria. Six iterations of questionnaires were required to reach consensus on wording of 53 final recommendations. Final recommendations covered initial management, evaluation, medical treatment, surgical treatment, and risk factor management. Interpretation: The final recommendations on the care of patients with transient ischemic attacks emphasize the importance of urgent evaluation and treatment. The novel approach used to develop these guidelines is feasible, allows for rapid updating, and may reduce bias.

Published
2006

15. The State of Stroke Clinical Research

Author

M. Cunningham and G. Hankey

Subjects
medicine.medical_specialty, Clinical research, Physical medicine and rehabilitation, business.industry, medicine, State (computer science), medicine.disease, business, Stroke
Published
2015

16. Therapeutic Response in Patients with Advanced Malignancies Treated with Combined Dendritic Cell–Activated T Cell Based Immunotherapy and Intensity–Modulated Radiotherapy

Author

Yukimasa Aoki, Kim G. Hankey, Dean L. Mann, Ryuko Watanabe, and Kenichiro Hasumi

Subjects
Cancer Research, Pathology, medicine.medical_specialty, medicine.medical_treatment, T cell, lcsh:RC254-282, Article, Cancer immunotherapy, medicine, dendritic cells, activated T-cells, combination immunotherapy, intratumoral injection, cancer vaccine, business.industry, Cancer, Dendritic cell, Immunotherapy, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, medicine.anatomical_structure, Oncology, Cancer research, Cancer vaccine, business, Adjuvant, Progressive disease
Abstract

Successful cancer immunotherapy is confounded by the magnitude of the tumor burden and the presence of immunoregulatory elements that suppress an immune response. To approach these issues, 26 patients with advanced treatment refractory cancer were enrolled in a safety/feasibility study wherein a conventional treatment modality, intensity modulated radiotherapy (IMRT), was combined with dendritic cell-based immunotherapy. We hypothesized that radiation would lower the tumor burdens, decrease the number/function of regulatory cells in the tumor environment, and release products of tumor cells that could be acquired by intratumoral injected immature dendritic cells (iDC). Metastatic lesions identified by CT (computed tomography) were injected with autologous iDC combined with a cytokine-based adjuvant and KLH (keyhole limpet hemocyanin), followed 24 h later by IV-infused T-cells expanded with anti-CD3 and IL-2 (AT). After three to five days, each of the injected lesions was treated with fractionated doses of IMRT followed by another injection of intratumoral iDC and IV-infused AT. No toxicity was observed with cell infusion while radiation-related toxicity was observed in seven patients. Five patients had progressive disease, eight demonstrated complete resolution at treated sites but developed recurrent disease at other sites, and 13 showed complete response at various follow-up times with an overall estimated Kaplan-Meier disease-free survival of 345 days. Most patients developed KLH antibodies supporting our hypothesis that the co-injected iDC are functional with the capacity to acquire antigens from their environment and generate an adaptive immune response. These results demonstrate the safety and effectiveness of this multimodality strategy combining immunotherapy and IMRT in patients with advanced malignancies.

Published
2011
Full Text
View/download PDF

17. Combining conventional therapies with intratumoral injection of autologous dendritic cells and activated T cells to treat patients with advanced cancers

Author

Kristina M. Harris, Ryuko Watanabe, Kim G. Hankey, Christina M. Celluzzi, Kenichiro Hasumi, and Dean L. Mann

Subjects
medicine.medical_treatment, T-Lymphocytes, Antigen-Presenting Cells, Breast Neoplasms, Lymphocyte Activation, Transplantation, Autologous, General Biochemistry, Genetics and Molecular Biology, Immune system, History and Philosophy of Science, Cancer immunotherapy, Antigen, Antigens, CD, Stomach Neoplasms, Neoplasms, Medicine, Humans, Lymphocytes, Chemotherapy, business.industry, General Neuroscience, Cancer, Dendritic Cells, HLA-DR Antigens, medicine.disease, Combined Modality Therapy, Radiation therapy, Response Evaluation Criteria in Solid Tumors, Culture Media, Conditioned, Immunology, Cancer research, Female, Cancer vaccine, business, Colorectal Neoplasms
Abstract

Dendritic cells (DCs) are potent antigen-presenting cells that have been used in cancer immunotherapy. To take advantage of the ability of DCs to acquire antigenic materials from their environment and generate primary as well as recall immune responses, 37 patients with advanced cancers were enrolled in a series of protocols based on direct intratumoral injection of immature DCs. To augment antigen uptake and antitumor immune response, DC injection was combined with radiotherapy or chemotherapy and/or injection of activated T cells. Treatments were well tolerated with no adverse reactions. Clinical responses were based on Response Evaluation Criteria in Solid Tumors, with the majority of patients showing stable disease. One of two patients who also received local radiation achieved a sustained complete response at injected and metastatic sites. The clinical responses observed in cancer patients with advanced disease suggest potential effectiveness of combination strategies and establish the basis for the current treatment protocol that is underway.

Published
2009

18. What Pathological Type of Stroke is it, Cerebral Ischaemia or Haemorrhage?

Author

G. Hankey, P. Langhorne, Joanna Wardlaw, Peter Sandercock, P. Rothwell, Charles Warlow, G. J. E. Rinkel, Martin Dennis, John Bamford, Catherine Sudlow, and J. van Gijn

Subjects
medicine.medical_specialty, medicine.diagnostic_test, business.industry, Internal medicine, Ischaemic stroke, medicine, Cardiology, Cerebral ischaemia, Magnetic resonance imaging, medicine.disease, business, Stroke, Pathological
Published
2008

19. Specific Treatment of Intracerebral Haemorrhage

Author

Martin Dennis, Charles Warlow, J. van Gijn, John Bamford, G. Hankey, G. J. E. Rinkel, Peter Langhorne, Joanna Wardlaw, Peter Sandercock, Cathie Sudlow, and P. Rothwell

Subjects
Hypocapnia, business.industry, Anesthesia, Medicine, business, medicine.disease, Pathophysiology, Intracranial pressure
Published
2008

20. Specific Treatments for Acute Ischaemic Stroke

Author

Peter Sandercock, Martin Dennis, John Bamford, G. J. E. Rinkel, G. Hankey, Charles Warlow, J. van Gijn, Catherine Sudlow, Joanna Wardlaw, P. Rothwell, and Peter Langhorne

Subjects
medicine.medical_specialty, business.industry, Internal medicine, Ischaemic stroke, medicine, Cardiology, medicine.disease, business, Thrombosis, Pathophysiology
Published
2008

21. What Caused This Intracerebral Haemorrhage?

Author

Peter Langhorne, Martin Dennis, Joanna Wardlaw, G. Hankey, John Bamford, Cathie Sudlow, Charles Warlow, P. Rothwell, J. van Gijn, G. J. E. Rinkel, and Peter Sandercock

Subjects
medicine.medical_specialty, business.industry, medicine, Subdural haematoma, medicine.disease, business, Caroticocavernous fistula, Surgery
Published
2008

22. A Practical Approach to the Management of Stroke and Transient Ischaemic Attack Patients

Author

G. Hankey, Martin Dennis, John Bamford, P. Langhorne, Peter Sandercock, Charles Warlow, Joanna Wardlaw, P. Rothwell, J. van Gijn, G. J. E. Rinkel, and Catherine Sudlow

Subjects
medicine.medical_specialty, business.industry, Internal medicine, Ischaemic stroke, medicine, Cardiology, Subarachnoid haemorrhage, Transient (computer programming), business, medicine.disease, Stroke
Published
2008

23. Is it a Vascular Event and Where is the Lesion?: Identifying and Interpreting the Symptoms and Signs of Cerebrovascular Disease

Author

Martin Dennis, John Bamford, Joanna Wardlaw, P. Langhorne, J. van Gijn, Catherine Sudlow, Charles Warlow, P. Rothwell, G. Hankey, G. J. E. Rinkel, and Peter Sandercock

Subjects
medicine.medical_specialty, business.industry, Event (relativity), medicine.disease, Lesion, Epilepsy, Internal medicine, Clinical diagnosis, Anesthesia, medicine, Cardiology, Subarachnoid haemorrhage, medicine.symptom, business, Transient monocular blindness
Published
2008

24. What Caused This Transient or Persisting Ischaemic Event?

Author

Martin Dennis, John Bamford, Peter Langhorne, J. van Gijn, G. J. E. Rinkel, G. Hankey, Peter Sandercock, Charles Warlow, Catherine Sudlow, P. Rothwell, and Joanna Wardlaw

Subjects
Embolism, business.industry, Event (relativity), Anesthesia, medicine, Churg-strauss syndrome, Transient (oscillation), medicine.disease, business
Published
2008

25. Unusual Causes of Ischaemic Stroke and Transient Ischaemic Attack

Author

Catherine Sudlow, Martin Dennis, Charles Warlow, John Bamford, P. Rothwell, G. Hankey, Peter Langhorne, Joanna Wardlaw, Peter Sandercock, J. van Gijn, and G. J. E. Rinkel

Subjects
medicine.medical_specialty, Pregnancy, Arterial dissection, business.industry, Internal medicine, Ischaemic stroke, medicine, Cardiology, Cancer, Transient (computer programming), medicine.disease, business, Surgery
Published
2008

26. Comparison of idraparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial fibrillation: a randomised, open-label, non-inferiority trial

Author

M G, Bousser, J, Bouthier, H R, Büller, A T, Cohen, H, Crijns, B L, Davidson, J, Halperin, G, Hankey, S, Levy, V, Pengo, P, Prandoni, M H, Prins, W, Tomkowski, C, Torp-Pedersen, C, Thorp-Pedersen, D, Chilson, ACS - Amsterdam Cardiovascular Sciences, and Vascular Medicine

Subjects
Male, medicine.medical_specialty, Vitamin K, Ximelagatran, medicine.drug_class, Idraparinux, Oligosaccharides, Hemorrhage, Kaplan-Meier Estimate, Risk Factors, Thromboembolism, Internal medicine, Atrial Fibrillation, medicine, Humans, Single-Blind Method, Stroke, Aged, Intention-to-treat analysis, business.industry, Acenocoumarol, Standard treatment, Anticoagulant, Hazard ratio, Warfarin, Anticoagulants, General Medicine, medicine.disease, Treatment Outcome, Anesthesia, Female, business, Factor Xa Inhibitors, medicine.drug
Abstract

BACKGROUND: Vitamin K antagonists, the current standard treatment for prophylaxis against stroke and systemic embolism in patients with atrial fibrillation, require regular monitoring and dose adjustment; an unmonitored, fixed-dose anticoagulant regimen would be preferable. The aim of this randomised, open-label non-inferiority trial was to compare the efficacy and safety of idraparinux with vitamin K antagonists. METHODS: Patients with atrial fibrillation at risk for thromboembolism were randomly assigned to receive either subcutaneous idraparinux (2.5 mg weekly) or adjusted-dose vitamin K antagonists (target of an international normalised ratio of 2-3). Assessment of outcome was done blinded to treatment. The primary efficacy outcome was the cumulative incidence of all stroke and systemic embolism. The principal safety outcome was clinically relevant bleeding. Analyses were done by intention to treat; the non-inferiority hazard ratio was set at 1.5. This trial is registered with ClinicalTrials.gov, number NCT00070655. FINDINGS: The trial was stopped after randomisation of 4576 patients (2283 to receive idraparinux, 2293 to receive vitamin K antagonists) and a mean follow-up period of 10.7 (SD 5.4) months because of excess clinically relevant bleeding with idraparinux (346 cases vs 226 cases; 19.7 vs 11.3 per 100 patient-years; p

Published
2008

27. Organised inpatient (stroke unit) care for stroke

Author

L. Kalra, Martin Dennis, N. L. Cabral, B.O. Williams, Lindsay Govan, G. Hankey, Elisabeth Hamrin, M. Britton, Christian Blomstrand, Graeme J. Hankey, Markku Kaste, S. O. Laursen, Bent Indredavik, P. Berman, Kjell Asplund, Christopher J. Weir, Paola Dey, A. Cavallini, and Peter Langhorne

Subjects
Patient Care Team, Medicine General & Introductory Medical Sciences, medicine.medical_specialty, Patient care team, 10 year follow up, business.industry, Stroke units, Rehabilitation unit, Stroke unit care, Prognosis, medicine.disease, law.invention, Stroke, Treatment Outcome, Randomized controlled trial, law, Emergency medicine, Ischemic stroke, medicine, Physical therapy, Humans, business, Hospital Units, Randomized Controlled Trials as Topic
Abstract

BACKGROUND: Organised stroke unit care is provided by multidisciplinary teams that exclusively manage stroke patients in a ward dedicated to stroke patients, with a mobile stroke team or within a generic disability service (mixed rehabilitation ward). OBJECTIVES: To assess the effect of stroke unit care compared with alternative forms of care for people following a stroke. SEARCH METHODS: We searched the trials registers of the Cochrane Stroke Group (January 2013) and the Cochrane Effective Practice and Organisation of Care (EPOC) Group (January 2013), MEDLINE (2008 to September 2012), EMBASE (2008 to September 2012) and CINAHL (1982 to September 2012). In an effort to identify further published, unpublished and ongoing trials, we searched 17 trial registers (January 2013), performed citation tracking of included studies, checked reference lists of relevant articles and contacted trialists. SELECTION CRITERIA: Randomised controlled clinical trials comparing organised inpatient stroke unit care with an alternative service. After formal risk of bias assessment, we have now excluded previously included quasi‐randomised trials. DATA COLLECTION AND ANALYSIS: Two review authors initially assessed eligibility and trial quality. We checked descriptive details and trial data with the co‐ordinators of the original trials. MAIN RESULTS: We included 28 trials, involving 5855 participants, comparing stroke unit care with an alternative service. More‐organised care was consistently associated with improved outcomes. Twenty‐one trials (3994 participants) compared stroke unit care with care provided in general wards. Stroke unit care showed reductions in the odds of death recorded at final (median one year) follow‐up (odds ratio (OR) 0.81, 95% Confidence Interval (CI) 0.69 to 0.94; P = 0.005), the odds of death or institutionalised care (OR 0.78, 95% CI 0.68 to 0.89; P = 0.0003) and the odds of death or dependency (OR 0.79, 95% CI 0.68 to 0.90; P = 0.0007). Sensitivity analyses indicated that the observed benefits remained when the analysis was restricted to securely randomised trials that used unequivocally blinded outcome assessment with a fixed period of follow‐up. Outcomes were independent of patient age, sex, initial stroke severity or stroke type, and appeared to be better in stroke units based in a discrete ward. There was no indication that organised stroke unit care resulted in a longer hospital stay. AUTHORS' CONCLUSIONS: Stroke patients who receive organised inpatient care in a stroke unit are more likely to be alive, independent, and living at home one year after the stroke. The benefits were most apparent in units based in a discrete ward. We observed no systematic increase in the length of inpatient stay.

Published
2007

28. Services for reducing the duration of hospital care for acute stroke patients

Author

G. Hankey and Peter Langhorne

Subjects
Advanced and Specialized Nursing, medicine.medical_specialty, Rehabilitation, business.industry, medicine.medical_treatment, medicine.disease, Hospital care, law.invention, Randomized controlled trial, law, Acute care, Emergency medicine, medicine, Neurology (clinical), Medical emergency, Duration (project management), Cardiology and Cardiovascular Medicine, business, Developed country, Stroke, Acute stroke
Abstract

In most developed countries, stroke patients are admitted to hospital for a period of acute care and rehabilitation. Services have been developed to try and accelerate discharge home and reduce the duration of hospital stay. These have been termed early supported discharge (ESD) services. This review tested whether ESD services could reduce length of stay and improve patient outcome compared with conventional hospital care and discharge arrangements. We searched the Cochrane Specialist Register of Controlled Trials (to August 2004). The contact trialist of all eligible studies was then contacted and asked to provide details of their intervention and control services and to provide individual patient data. We included randomized controlled trials (RCTs) that compared an ESD service with conventional care for hospitalized stroke …

Published
2006

29. MIC expression in renal and pancreatic allografts

Author

Thomas Spies, Benjamin Philosophe, David K. Klassen, Kim G. Hankey, S. T. Bartlett, Dean L. Mann, Cinthia B. Drachenberg, John C. Papadimitriou, and Veronika Groh

Subjects
Pathology, medicine.medical_specialty, medicine.medical_treatment, Biopsy, Biology, Pancreas transplantation, Kidney, Antigen, medicine, Humans, Transplantation, Homologous, Pancreas, Kidney transplantation, Acute tubular necrosis, Transplantation, medicine.diagnostic_test, Histocompatibility Antigens Class I, medicine.disease, Immunohistochemistry, Kidney Transplantation, medicine.anatomical_structure, Pancreas Transplantation
Abstract

Background. MHC class I chain-related antigen A (MICA) and MHC class I chain-related antigen B (MICB) are HLA class I related products of polymorphic MHC genes. Constitutive expression in normal tissue is limited to gut epithelium but can be induced in other epithelial cells by stress. Specific antibodies against MICA have been reported in the serum of patients who had rejected kidney allografts, suggesting a potential role for these molecules in transplant immunopathology. However, expression of MICA and MICB in transplanted organs has not been demonstrated. In this study, we report the expression of MICA and MICB in renal and pancreatic allograft biopsies, which were obtained due to clinical signs of rejection. Methods. A monoclonal antibody directed against MICA and MICB was used to perform indirect immunohistochemistry on formalin fixed, paraffin embedded needle biopsies of kidney and pancreas allografts. The results of staining were then compared to the standard light microscopic evaluation of the biopsies for rejection. Results. A total of 53 individual renal transplant biopsies and 19 pancreas transplant biopsies were assayed for expression of MIC. Histologically, renal biopsies were diagnosed as no rejection, acute tubular necrosis (ATN), acute rejection (AR), chronic rejection (CR), and acute and chronic rejection (ACR). No staining was observed in 7 of 10 kidneys showing no rejection. All 11 of the kidney biopsies with AR were positive, as were the 11 ATN cases, 9 of the 11 kidney biopsies with CR, and 7 of the 10 with ACR. The acini of normal, nontransplanted, pancreas, control specimen were consistently negative; however, islets were positive in all specimens. The acini and islets of five histologically normal pancreas biopsies were positive, as were the four biopsies with AR, seven biopsies with CR, and two with ACR. Conclusions. MICA and MICB are expressed in epithelial cells in allografted kidney and pancreas that show histologic evidence of rejection and/or cellular injury. In addition to previous findings of alloantibodies against MICA, expression of these gene products may play a role in allograft rejection.

Published
2002

Catalog

Books, media, physical & digital resources
See catalog results