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1. Carotid endarterectomy or stenting or best medical treatment alone for moderate-to-severe asymptomatic carotid artery stenosis: 5-year results of a multicentre, randomised controlled trial

Author

Tilman Reiff, Hans-Henning Eckstein, Ulrich Mansmann, Olav Jansen, Gustav Fraedrich, Harald Mudra, Dittmar Böckler, Michael Böhm, E Sebastian Debus, Jens Fiehler, Klaus Mathias, Erich B Ringelstein, Jürg Schmidli, Robert Stingele, Ralf Zahn, Thomas Zeller, Wolf-Dirk Niesen, Kristian Barlinn, Andreas Binder, Jörg Glahn, Werner Hacke, Peter Arthur Ringleb, Friedhelm Beyersdorf, Roland-Richard Macharzina, Gabriele Lechner, Carolin Menz, Sabine Schonhardt, Michael Weinbeck, Olga Greb, Dagmar Otto, Thomas Winker, Hermann Berger, Holger Poppert, Andreas Kühnl, Volker Pütz, Kathrin Haase, Ulf Bodechtel, Norbert Weiss, Hendrik Bergert, Johannes Meyne, Justus Groß, Matthias Kruse, Berthold Gerdes, Wolf-Dieter Reinbold, Helge Wuttig, Andreas Maier-Hasselmann, Manuela Segerer, Hans-Hermann Fuchs, Sabine Gass, Christoph Groden, Marco Niedergethmann, Martin Griebe, Michael Rosenkranz, Jürgen Beck, Götz Thomalla, Hermann H. Zeumer, Marek Jauß, Werner Kneist, Martina Kneist, Thomas Staudacher, Alfons Bernhard, Petra Jost, Nico Prey, Jürgen Knippschild, Oliver Kastrup, Martin Köhrmann, Benedikt Frank, Volkmar Bongers, Johannes Hoffmann, Horst-Wilhelm Kniemeyer, Michael Knauth, Kathrin Wasser, Tomislav Stojanovic, Hans Emmert, Josef Tacke, Bernhard Schwalbe, Eun-Mi Nam, Ulrike van Lengerich, Stephan Lowens, Klaus Gröschel, Timo Uphaus, Sonja Gröschel, Stephan Boor, Bernhard Dorweiler, Elisabeth Schmid, Hans Henkes, Thomas Hupp, Oliver Singer, Gerhard Hamann, Michaela Wagner-Heck, Sibylle Kerth-Krick, Metin Kilic, Peter Huppert, Kurt Niederkorn, Johannes Fruhwirth, Günther Klein, Ulrich Pulkowski, Karsten Jöster, Jens-Henning Wacks, Egbert Kloppmann, Bijan Vatankhah, Silke Hopf-Jensen, Henning Stolze, Stefan Müller-Hülsbeck, Knut Peer Walluscheck, Hans-Michael Schmitt, Albert Grüger, Jörg Seemann, Belay Tilahun, Martin Dichgans, Frank Arne Wollenweber, Angelika Dörr, Adelgunde Zollver, Gabor Gäbel, Günter Hedtmann, Rainer Kollmar, Detlef Claus, Christian Petermann, Stefanie Kirsch, Branko Bosnjak, Johannes Heiß, Holger Mühling, Silke Wunderlich, Peter Nikolaus Sabisch, Georg Gahn, Martin Storck, Sebastian Arnold, Urs Fischer, Jan Gralla, Matthias von Mering, Rüdiger Dißmann, Delia Kirsch, Christoph Schmidauer, Peter Waldenberger, Martin Furtner, Haiko Kazarians, Peter Breuer, Christian Arning, Jürgen Rieper, Georg Schmidt, Marcel Arnold, Gerhard Schroth, Jens Weise, Jürgen Zanow, Thomas Mayer, Rudolf Töpper, Walter Gross-Fengels, Harald Daum, Ralf Dittrich, Martin Ritter, Bernd Kasprzak, Giovanni Torsello, Carsten Pohlmann, Roland Brüning, Alexander Crispin, Miriam Hofmann, Thomas Müller, Erwin Blessing, Markus Möhlenbruch, Ines Ludwig, and Hemasse Amiri

Subjects
Stroke, Endarterectomy, Carotid, Treatment Outcome, Humans, Carotid Stenosis, Stents, Neurology (clinical), Brain Ischemia, Ischemic Stroke
Abstract

The optimal treatment for patients with asymptomatic carotid artery stenosis is under debate. Since best medical treatment (BMT) has improved over time, the benefit of carotid endarterectomy (CEA) or carotid artery stenting (CAS) is unclear. Randomised data comparing the effect of CEA and CAS versus BMT alone are absent. We aimed to directly compare CEA plus BMT with CAS plus BMT and both with BMT only.SPACE-2 was a multicentre, randomised, controlled trial at 36 study centres in Austria, Germany, and Switzerland. We enrolled participants aged 50-85 years with asymptomatic carotid artery stenosis at the distal common carotid artery or the extracranial internal carotid artery of at least 70%, according to European Carotid Surgery Trial criteria. Initially designed as a three-arm trial including one group for BMT alone (with a randomised allocation ratio of 2·9:2·9:1), the SPACE-2 study design was amended (due to slow recruitment) to become two substudies with two arms each comparing CEA plus BMT with BMT alone (SPACE-2a) and CAS plus BMT with BMT alone (SPACE-2b); in each case in a 1:1 randomisation. Participants and clinicians were not masked to allocation. The primary efficacy endpoint was the cumulative incidence of any stroke or death from any cause within 30 days or any ipsilateral ischaemic stroke within 5 years. The primary safety endpoint was any stroke or death from any cause within 30 days after CEA or CAS. The primary analysis was by intention-to treat, which included all randomly assigned patients in SPACE-2, SPACE-2a, and SPACE-2b, analysed using meta-analysis of individual patient data. We did two-step hierarchical testing to first show superiority of CEA and CAS to BMT alone then to assess non-inferiority of CAS to CEA. Originally, we planned to recruit 3640 patients; however, the study had to be stopped prematurely due to insufficient recruitment. This report presents the primary analysis at 5-year follow-up. This trial is registered with ISRCTN, number ISRCTN78592017.513 patients across SPACE-2, SPACE-2a, and SPACE-2b were recruited and surveyed between July 9, 2009, and Dec 12, 2019, of whom 203 (40%) were allocated to CEA plus BMT, 197 (38%) to CAS plus BMT, and 113 (22%) to BMT alone. Median follow-up was 59·9 months (IQR 46·6-60·0). The cumulative incidence of any stroke or death from any cause within 30 days or any ipsilateral ischaemic stroke within 5 years (primary efficacy endpoint) was 2·5% (95% CI 1·0-5·8) with CEA plus BMT, 4·4% (2·2-8·6) with CAS plus BMT, and 3·1% (1·0-9·4) with BMT alone. Cox proportional-hazard testing showed no difference in risk for the primary efficacy endpoint for CEA plus BMT versus BMT alone (hazard ratio [HR] 0·93, 95% CI 0·22-3·91; p=0·93) or for CAS plus BMT versus BMT alone (1·55, 0·41-5·85; p=0·52). Superiority of CEA or CAS to BMT was not shown, therefore non-inferiority testing was not done. In both the CEA group and the CAS group, five strokes and no deaths occurred in the 30-day period after the procedure. During the 5-year follow-up period, three ipsilateral strokes occurred in both the CAS plus BMT and BMT alone group, with none in the CEA plus BMT group.CEA plus BMT or CAS plus BMT were not found to be superior to BMT alone regarding risk of any stroke or death within 30 days or ipsilateral stroke during the 5-year observation period. Because of the small sample size, results should be interpreted with caution.German Federal Ministry of Education and Research (BMBF) and German Research Foundation (DFG).

Published
2022
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2. Multiple Sklerose und COVID-19

Author

Matthias von Mering

Subjects
2019-20 coronavirus outbreak, Immunsystem, Impfen, Coronavirus disease 2019 (COVID-19), Schlüsselwörter: Multiple Sklerose, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Medicine, business, Virology, Pflege Kolleg, COVID
Published
2021

3. The Changing Landscape for Stroke Prevention in AF

Author

Mercedes Samson, Siegfried Frickel, Hirosi Meno, Niels Gadsbøll, Sébastien Prévôt, Sorin Alexandru Antonescu, Xiaodong Li, Tetsuya Haruna, Zicheng Li, Catarina Fonseca, Ralf Zahn, Shahid Aziz, Takashi Tsutsui, Galal Kerfes, Elisabeth Louise Zeuthen, Lluís Mont, Angelika Tamm, Bogdan Minescu, Eric Lo, Gerardo Ansalone, Malcolm Foster, Tristan Mirault, Nabil Andrawis, Apostolos Katsivas, Imad Kreidieh, Juliano Novaes Cardoso, Margaret Ikpoh, Dimitar Raev, Said Chaaban, Dan Tesloianu, Philippe Loiselet, Joachim Gmehling, Joseph Hakas, Steven Forman, Ernst Günter Vester, Bettina Schmitz, Hassan El-Sayed, Hiroshi Tsutsui, Salvatore Pirelli, Jens Taggeselle, Arnljot Tveit, David Smith, Manuel De Los Rios Ibarra, Rafael Salguero, Jindrich Spinar, Vanja Bašić Kes, Jose Walter Cabrera Honorio, Adrien Salem, Gavino Casu, Jean Michel Quedillac, Ana Fruntelata, Peter Siostrzonek, Dmitry Napalkov, Luthando Adams, Valeria Calvi, Jeff S. Healey, Magnus Forsgren, Larisa Kalinina, Ratika Parkash, P. F.M.M. Bergen van, Carmen Manuela Muresan, H. Gorka, Andreas Mügge, Gustavo Maid, Serge Yvorra, Alexander Paraschos, Bernhard Witzenbichler, Viktor Peršić, Jeong Su Kim, Dong Jin Oh, Yutaka Furukawa, Steve Compton, Ravikiran Korabathina, Tammam Al-Joundi, Muzahir H. Tayebjee, Robert Betzu, David J. Cislowski, Alon Steinberg, Carisi Anne Polanczyk, Sanjiv Petkar, Andy Lam, Mingsheng Wang, Galina Ivanchura, Ruediger Seebass, Thomas Guarnieri, Seth H. Baker, Paula Carvalho, Brian First, Konstantinos Makaritsis, Alex C. Spyropoulos, Mohiburrahman Sirajuddin, Richard Bala, David Goldscher, G. Larsen Kneller, Ki Seok Kim, Sherman Tang, Venkat Iyer, Payman Sattar, Yamile Porro, Gregory Y.H. Lip, Christa Raters, Olivier Gartenlaub, Elizaveta Panchenko, Niccolo' Marcionni, Ole Nyvad, Sibel Zehra Aydin, Kenji Kawajiri, Dipankar Dutta, Gabriel Contreras Buenostro, Shaival Kapadia, Harry J.G.M. Crijns, Miroslav Rubacek, Myriam Brunehaut, Igor Diemberger, Kyle Rickner, Katsumi Tanaka, Moon Hyoung Lee, Pamela Nerheim, Jose Carlos Moura Jorge, Michael Gumbley, Katie Randall, Francesco Melandri, Sunil Chand, Harukazu Iseki, Thalie Traissac, Ningfu Wang, Ghiath Mikdadi, Peter D. Schellinger, Andrew M. Rubin, Conrad Genz, Karl Heinz Seidl, Maurice Pye, Giorgio Annoni, Adalberto Menezes Lorga Filho, William H. Pentz, Lisa Schmitz, Gary Miller, Didier Smadja, Elena Khludeeva, David Hargroves, Hans-Christoph Diener, Tiziano Moccetti, Azlisham Mohd Nor, Kai Koenig, F. A. Rooyer, Kiyoo Mori, Carlos Gonzalez Juanatey, Jan Beyer-Westendorf, Charles Landau, Steven B Eisenberg, Hugh F. McIntyre, Emilio Gonzalez Cocina, Erik May, Gyo-Seung Hwang, Alberto Giniger, Karl-Heinz Kuck, Yan Carlos Duarte Vera, Vladimir Gorbunov, Priya Nair, Shih Ann Chen, Beat J. Meyer, Donghui Zhang, Feng Wang, Richard J.H. Smith, Michele Massimo Gulizia, Darko Pocanic, Abul Azim, Jose Maria Lobos, Patrick Leprince, Peter Vanacker, Marica Bracic Kalan, James Crenshaw, Ewa Nowalany-Kozielska, Ayham Al-Zoebi, Eiji Hishida, Louis Essandoh, Younghoon Kim, Yanmin Yang, Dhiraj Gupta, Fausto J. Pinto, Arnold Pinter, Stanley Koch, Luis Felipe Pezo, Dzifa Wosornu Abban, Martin S. Green, Chrystalenia Kafkala, Zhitao Liu, Jose Luis Llisterri, Su Mei Angela Koh, Lin Chih-Chan, Ruth Davies, Ursula Rauch-Kroehnert, Julio Tallet, Juan Benezet-Mazuecos, Andreas Kastrup, Rohit Malhotra, Serge Timsit, Thierry Frappé, Kostas Oikonomou, Ameer Kabour, Kishor Vora, Douglas Roberts, Carlos Scherr, Pedro Dionísio, Nicoleta Violeta Miu, Eve Gillespie, Petr Povolny, F.R. Grondin, Philippe Lyrer, Raymond Fisher, Philip O'Donnell, Nima Amjadi, Juan Vazquez, Lynn Corbett, Patrick Peters, Jing Zhou, Thomas Kümler, Danny H.K. Wong, Evaldas Giedrimas, William McGarity, Frank L. Silver, Emmanuel Touzé, Ana Leitão, Suk keun Hong, Marwan Salfity, Constantin Militaru, S T Matskeplishvili, Johannes A. Kragten, Sam Henein, Anthony D'Souza, B. J. Krenning, Francesco Chiarella, Rene Casanova, Stephan Willems, Yong Keun Cho, Tae Joon Cha, Stewart Pollock, Rajendra Moodley, Rosa Ysabel Cotrina Pereyra, Volker Laske, Zhanquan Li, Kenneth B. Harris, Johnny Dy, Gabriele Guardigli, Hisham Kashou, Norberto Matadamas Hernandez, Zdravka Poljaković, E. Decoulx, Paul Wakefield, Sung Ho Her, Fatma Qaddoura, Giuseppe Boriani, Younus Ismail, Franz Goss, Shigeru Fujii, J. R. Groot de, Ming Shien Wen, Rui Candeias, Thomas Rebane, Juan Carlos Arias, Robert Jobe, Nicolas Ley, Taishi Sasaoka, Luigi Ria, Jonathan Banayan, Paul McLaughlin, Sergei Zenin, Luis E. Martinez, Thuraia Nageh, Fabrizio Ammirati, M. E.W. Hemels, Yutaka Shimizu, Elina Trendafilova, Maxime Fayard, Randeep Suneja, Attilia Maria Pizzini, Mark B. Abelson, Rabih R. Azar, Jian Zhou, Valerie Bockisch, Martin Koschutnik, James Hitchcock, Vlad Ciobotaru, Didier Irles, Patrik Michel, Witold Streb, John F. Corrigan, Ajit Singh Khaira, Marco Antônio Mota Gomes, Richard Tytus, Christian Hall, Antonius Ziekenhuis, Catherine Mallecourt, David J. Williams, Doo Il Kim, Brian Gordon, Salvatore Novo, Soufian Al Mahameed, Anil Shah, N. Joseph Deumite, Brent T. McLaurin, Ruth H. Strasser, Somnath Kumar, Genshan Ma, Aurel Cracan, Rajiv Mallik, Anthony Vlastaris, Francesco Perticone, Julio Alberto Aguilar Linares, Angel Moya, William Ashcraft, Steven Lupovitch, Renate Weinrich, Ralph F. Bosch, Gerald Ukrainski, Jon Arne Sparby, Norbert Schön, Pierre Jean Scala, Steven E. Hearne, Mark Roman, Ramin Farsad, Werner Rieker, Guillaume Cayla, Ramon Freixa, Hidemitsu Nakagawa, Kunihiro Nishida, Thomas J. Mulhearn, Tak W. Kwan, Jeffrey Shanes, Tiziana Tassinari, Ka Sing Lawrence Wong, Kneale Metcalf, Dominique Lejay, Daniel Savard, Pierre Chevallereau, Gilles O'Hara, Milan Mikus, Hiroshi Fukunaga, Olga Korennova, Xavier Ducrocq, Edvard Berngard, Mario Bo, Hoi Fan Chow, E. Ronner, Yuriy Grinshstein, Amparo Mena, Sidiqullah Rahimi, Axel Brandes, Shigenobu Bando, Freddy Del-Carpio Munoz, Jonathan L. Halperin, Ronald D. Jenkins, Carlos Rodríguez Pascual, Alain Lacroix, Sergio Agosti, Franklin Handel, Aylmer Tang, Nan Jiang, Diana A. Gorog, Dimitrios Stakos, Gerald Greer, Dudley Goulden, Martin Grond, Oran Corey, Stellan Bandh, Efrain Gonzalez, Alexander Klein, Jacques Scemama, Amelie Elsaesser, Nathan Foster, Francesco Fedele, Dinesh Mistry, Alberto Caccavo, Bjørn Bratland, Jean Marc Davy, D. J. Boswijk, Abdullah Al Ali, Muhammad Khalid, Terry McCormack, Clare Seamark, Enrico Passamonti, Zoran Olivari, Simon W Dubrey, Wlodzimierz Musial, Antonio Martín Santana, Jianqiu Liang, Manuel de Mora, Dmitry Dupljakov, Nicholas Jones, Mohamed Alshehri, Paul Charbel, John Bullinga, Petr Polasek, Hossein Almassi, Reza Mehzad, Gamal Hussein, Marcus Wiemer, Ali Sharareh, Alexandra Finsen, David Huckins, Denis Angoulvant, Matthias Leschke, Craig Vogel, Stefan Schuster, Juan E. Mesa, Yong Seog Oh, Axel De La Briolle, Jacek Kowalczyk, Louise Shaw, Eduardo de Teresa, Stefan Naydenov, Hubert Vial, Ian I Joffe, Christoph Kleinschnitz, Takeshi Yamashita, A. Salvioni, Aman M. Shah, Michael Renzi, Claude Brunschwig, Ioannis Styliadis, Ravi Bhagwat, Julian Coronel, Asok Venkataraman, Zayd Eldadah, Dinesh Singal, Byung Chun Jung, Michael Lillestol, Mirza S. Baig, Jose Polo, Ira Dauber, Olga Barbarash, Kristina Zint, Pavel Galin, P. J. A. M. Brouwers, Ki Byeong Nam, Andrey Ezhov, Kevin F. Browne, Iveta Sime, Tetsuo Sakai, Jean Louis Georges, Manish Jain, Alexey Nizov, Jean Dillinger, Arif Elvan, John Barton, Rainer Zimmermann, Junji Kanda, Clare Holmes, Werner Jung, Aurélien Miralles, Tatiana Novikova, Steven Georgeson, Yorihiko Higashino, Akira Yamada, David Sprigings, Haroon Rashid, J. W.M. Eck van, Bernard Erickson, Barry Seidman, Koji Kajiwara, Kannappan Krishnaswamy, Daniel Ferreira, Sébastien Armero, Brian Wong, Dong Gu Shin, Ludovic Chartier, Priit Kampus, Francisco Marín, Rickey Manning, Martin Köhrmann, Edward J. Kosinski, Bengt Johansson, Y. S. Tuininga, Simon Cattan, Sergio Dubner, Imran Dotani, Wenchi Kevin Tsai, Gregorio Sanchez, Edwin Blumberg, Charles Crump, Frank Jäger, Christoforos Olympios, Matthew Hoghton, Xinwen Zhao, Derek Muse, Alexandre Guignier, Toby Black, Yuichiro Takagi, Phil Keeling, Richard A. Bernstein, Omar Elhag, Jean Ernst Poulard, Fernando Gabriel Manzur Jattin, James Hampsey, Shahid Mahmood, Steffen Behrens, Tianlun Yang, Elena Dotcheva, Krishnan Challappa, Nam Ho Kim, Claudio Cavallini, Eric Espaliat, Martin James, June Soo Kim, Marc Roelke, Harold Thomas, Charles A. Shoultz, Rami El Mahmoud, José Francisco Kerr Saraiva, Jürgen vom Dahl, Xuebo Liu, Dong Ju Choi, Sergio Mondillo, Ian Parker, Kazuya Yamamoto, Rafael Martin Suarez, Karla M. Kurrelmeyer, Akber Mohammed, Nikitas Moschos, Benoit Coutu, Georgios Hananis, Hamed M. Zuhairy, Giovanni Baula, Suchdeep Bains, Menno V. Huisman, Heng Jiang, Jaroslaw Sek, Yoto Yotov, Malik Ali, Dalmo Antonio Ribeiro Moreira, Torben Larsen, Raed Osman, Marie Paule Houppe Nousse, Shulin Wu, Arturo Raisaro, Efrain Alonso Gomez Lopez, Violeta Cindea Nica, Eduardo Julián José Roberto Chuquiure Valenzuela, Wladmir Faustino Saporito, Changsheng Ma, Francesco Romeo, Jorge Martínez, M. Shakil Aslam, Kenneth J. Rothman, Kamal Al Ghalayini, Magdy Mikhail, Charles Augenbraun, Andreas Wilke, Peter Goethals, John D. McClure, Humberto Rodriguez Reyes, Peter Schoeniger, Nabil Jarmukli, Elizabeth S. Kaufman, Nathalie Duvilla, Jens Wicke, Kausik Chatterjee, Philippe Audouin, Dragan Kovacic, Xingwei Zhang, Brad Frandsen, Alberto Conti, Francisco Aguilar, Sasalu Deepak, Geir Heggelund, David S. Rosenbaum, Sergey P. Golitsyn, Alessandro Capucci, Rodolfo Sotolongo, Begoña Sevilla, François Poulain, Thomas Ronzière, Naseem Jaffrani, Dominik Michalski, Jose Lopez-Sendon, Silvia Di Legge, Bernard Jouve, Chang Sheng Ma, Robert Parris, Sumeet K. Mainigi, Jing Yao, Lars Udo Krause, Ulrich Tebbe, Quansan Zhang, Mathieu Amelot, Peter Crean, Benzy J. Padanilam, Nicolas Breton, Fernando Tomas Lanas Zanetti, Subhash Banerjee, Andrew I. Cohen, Michel Galinier, Jacek Miarka, Gerian Grönefeld, Vicente Bertomeu, Mariusz Gierba, Danny, Anna Ferrier, Luciano Marcelo Backes, Lianqun Cui, Eun-Seok Shin, Andreas Meinel, Jay Koons, Jen Yuan Kuo, Brett Graham, Antonio Garcia Quintana, Michael Hill, Sylvain Destrac, Janko Szavits-Nossan, Shanglang Cai, Joaquín Osca, Luis Aguinaga, Hemal M. Nayak, Chander Arora, Shinji Tayama, Diana Delić Brkljačić, Tiemin Jiang, Miguel Agustin Reyes Rocha, Ronan Collins, Davide Imberti, Kwang Soo Cha, Matthias Gabelmann, Alfredo Astesiano, Christian Weimar, William Eaves, Tatiana Ionova, Khalid Almuti, Thierry Schaupp, Bernhard Paul Lodde, Darlene Elias, Yuichiro Nakamura, Raed Al-Dallow, Eric Parrens, Weihua Li, Alan Bell, Noah Israel, Nadezda Rozkova, Nediljko Pivac, Nooshin Bazargani, Armando Pineda-Velez, Hyung Wook Park, Amin Karim, Clemens Steinwender, Davor Milicic, Gonzalo Barón, Robert Topkis, Mehrdad Ariani, Craig S. Barr, Paulo Bettencourt, Roberto Zanini, Andrew Moriarty, Pascal Goube, Fausto Rigo, Irene Madariaga, Atsushi Sueyoshi, Małgorzata Lelonek, Kevin R. Wheelan, Richard Huntley, Donald Brautigam, Jacek Gniot, Ido Lori, Dragos Vinereanu, Daniel Lee, Kouki Watanabe, Michael Vargas, Natalya Koziolova, James S. Zebrack, Basel Hanbali, Cesare Greco, José Luis Zamorano, Rajesh Patel, Fernando Carvalho Neuenschwander, Sergio Luiz Zimmermann, Shuiping Zhao, Pedro Adragão, Karl Heinz Schmitz, Abdelfatah Alasfar, Olga Ferreira de Souza, David N. Pham, Mark Dayer, Thomas Davee, Yoshiki Hata, Mika Skeppholm, Martin O'Donnell, David Molony, Joe Hargrove, Hani Sabbour, Pascal Defaye, Jochen Bott, Dora Ines Molina de Salazar, Anthony Clay, Giancarlo Landini, Michael McGuire, Dae Kyeong Kim, A. Shekhar Pandey, Bouziane Benhalima, Serge Cohen, Aamir Cheema, Matthias Claus, Marcus L. Williams, Qiangsun Zheng, Karim Bakhtiar, Hailong Lin, Sergio Berti, David Hartley, Libor Nechvatal, Rami Mihail Chreih, Domingo Pozzer, James Capo, John Floyd, Bhola Rama, Harald Darius, Ioannis Mantas, Pareed Aliyar, Carlos Barrera, Galina Ketova, Mark Chang, Alan J. Bank, José Ferreira Santos, Samir Turk, Lakshmanan Sekaran, Adam Ellery, Aurélie Buhl, Naomasa Miyamoto, Kuo Ho Yeh, Nicolas Mousallem, Hassan Soda, Dimitrios J. Richter, Zhaohui Wu, Tim Edwards, Kai Sukles, Koji Maeno, Huanyi Zhang, Paolo Verdecchia, Alexandros Gkotsis, Joe Pouzar, Philippe Berdagué, Edoardo Gronda, Olesya Rubanenko, Cristian Podoleanu, Mariano Ruiz Borret, Guillermo Llamas Esperon, Iveta Mintale, Hideki Shimomura, Dadong Zhang, Angelo Amato Vicenzo de Paola, Kenneth Butcher, Pascal Tessier, Minang Turakhia, Peter Svensson, Shabbir Reza, Herbert Pardell, Wilfried Lang, Holger Poppert, Alan Ackermann, Olivier Citerne, Emil Hayek, Yang Zheng, Jin bae Kim, Lorenzo Fácila, Tetsuo Hisadome, Li Sun, Panagiotis Vardas, Angel Grande, Piers Clifford, C. Zwaan van der, Nicki Law, Ilsbe Salecker, Steven Isserman, Shozo Tanaka, Dorothee B. Bartels, Yann Hemery, Susanna Cary, Mehiar El-Hamdani, Indira Natarajan, Miney Paquette, C. Wilson Sofley, Charles C. Gornick, Fu-Tien Chiang, Ellen Bøhmer, Hiroki Yamanoue, Toru Nakayama, Chakri Yarlagadda, Ciro Indolfi, Narendra Singh, Juan Carlos Nunez Fragoso, Eisho Kyo, Laurent Deluche, Andreas Götte, Stephen Phlaum, Jong Sung Park, Paresh Mehta, Terrence C. Hack, Fred Cucher, Olivier Dibon, Chia Theng Daniel Oh, Shannon Twiddy, Sean Connors, Edo Bottacchi, Beata Wożakowska-Kapłon, Ronald B. Goldberg, Jordi Bruguera, James J. Kmetzo, Jeanne Wei, John Kazmierski, Pilar Mazón, M Frais, Kazuya Kawai, Dimitrios Alexopoulos, Abayomi Osunkoya, Wanda Sudnik, Ramon Horacio Limon Rodriguez, William J. French, Ira Lieber, Rajesh Aggarwal, Stuart W. Zarich, John A. Puleo, David Cudmore, Jost Henner Wirtz, Ute Altmann, Kyung Tae Jung, Jennifer Litchfield, Jei Keon Chae, Rainer Dziewas, James Neiman, Karin Rybak, Galina Chumakova, Riccardo Pini, Richard Oliver, Benoit Lequeux, Athanasios J. Manolis, Luisa Fonseca, César A. Jardim, Katsuhiro Matsuda, Paul Hermany, Ming Luo, Ronnie Garcia, Oscar Pereira Dutra, John Culp, Amrit Pal Singh Takhar, Victor Howard, Oyidie Igbokidi, Kuo Yang Wang, Britta Goldmann, Thomas Walter, Mohamed K. Al-Obaidi, Antonio Pose, Christine Teutsch, Arthur J. Labovitz, Thomas Folk, Nell Wyatt, A. Huizenga, Benhur Henz, Konstantin Protasov, Petra Maskova, Ioannis Goudevenos, Kier Huehnergarth, Elena Kinova, Georgios Stergiou, Guohai Su, Hüseyin Ince, Chi Hung Huang, Winfried Haerer, Saad Al Ismail, Michael Gabris, Brian Carlson, Feng Liu, Yansheng Li, Luis Gustavo Gomes Ferreira, Radosław Lenarczyk, Ruben Omar Iza Villanueva, Nandkishore Ranadive, Yong Xu, Oscar Saenz Morales, Wayne Turner, Aleksey Khripun, Paul G. Grena, Yusuke Fujino, Abraham Salacata, Aleksandar Knezevic, Fouad Elghelbazouri, Hamid Bayeh, Mikhail Torosoff, Martin Cooper, Alenka Mavri, Marina Freydlin, Vassilios Vassilikos, Naresh Ranjith, Laurent Prunier, E. Hoffer, George Mitchell, Javier León Jiménez, S.S. Kabbani, Waldemar Krysiak, Emmanuel Nsah, John Ip, Charles B. Eaton, Jérome Thevenin, Dimitrios Chrysos, Asaad Bakbak, L. Steven Zukerman, Maria Grazia Bongiorni, Matthias von Mering, Lisa Alderson, Jean Joseph Muller, Yann Jamon, Roger Moore, Harinath Chandrashekar, Athanasios Pras, Venkatesh Nadar, B. J. Berg van den, Tomas Ripoll, Eric Van De Graaff, Patrick Dary, Peter L. Schwimmbeck, James Poock, Robert Schnitzler, Rohit Arora, Vuong DuThinh, Uwe Gremmler, Nuno Raposo, Chirag Sandesara, Ping Yen Bryan Yan, Junya Shite, Andrea Berz, Isabel Egocheaga, Karine Lavandier, Jose M. Teixeira, Ewart Jackson-Voyzey, Mayar Jundi, Ignacio Iglesias, Stephen Bloom, Hans Rickli, Rudolph Evonich, Giulio Molon, Vinay Shah, Salvador Bruno Valdovinos Chavez, Walter Ageno, Mauro Esteves Hernandes, Ali Ghanbasha, Stefan Regner, Luc De Wolf, Abdel El Hallak, Mohammad Shoukfeh, Francesco Musumeci, Pablo Andres Sepulveda Varela, Gershan Davis, Xianyan Jiang, Matthew Ebinger, Xiangdong Xu, Andreas Winkler, T. A. Simmers, Olivier Dascotte, Dominique Magnin, Karen Mahood, Carolina Guevara Caiedo, Zulu Wang, Hung-Fat Tse, John Camm, Didier Cadinot, Javier Aguila Marin, Juan Jose Olalla, Tamara Everington, Sherryn Roth, Feliz Alvaro Medina Palomino, Gregg Coodley, Wenhui Liu, G. Y. H. Lip, Ricky Ganim, Paul Ainsworth, Luiz Eduardo Fonteles Ritt, Yalin Liu, Sung Won Jang, Percy Berrospi, Dhananjai Menzies, Julien Pineau, Robert J. Jeanfreau, Hervé Buathier, John D. Osborne, Ted S. N. Lo, Li Fern Hsu, Xi Su, Beate Wild, Alvaro Rabelo Alves, Tomas Cieza-Lara, Neeraj Prasad, Yoshinori Seko, Jaydutt Patel, Malte Kuniss, Guy Chouinard, Jacek Morka, Frank Rubalcava, Fran Adams, Ignacio Rodriguez Briones, Vivek Sharma, Xinhua Wang, Amir Malik, Walid Amara, Adnan El Jabali, José Arturo Maldonado Villalon, Frederic Georger, Hong Ma, Steffen Schnupp, Nolan Mayer, Adam Sokal, Nasser Abdul, Gérald Phan Cao Phai, Jorge Hugo Blanco Ibaceta, Ramakrishnan Iyer, Yves Cottin, Barry Troyan, Achim Küppers, Anastas Stoikov, Jasjit Walia, Bruce Iteld, Abdul Alawwa, Christos Milonas, Frank Mibach, Mahfouz El Shahawy, H.William Stites, Neerav Shah, Clifford Ehrlich, Zia Ahmad, Furio Colivicchi, and Laszlo Karolyi

Subjects
medicine.medical_specialty, business.industry, Atrial fibrillation, 030204 cardiovascular system & hematology, medicine.disease, Dabigatran, 03 medical and health sciences, 0302 clinical medicine, Stroke prevention, Antithrombotic, Emergency medicine, medicine, In patient, 030212 general & internal medicine, Cardiology and Cardiovascular Medicine, Intensive care medicine, Prospective cohort study, business, Stroke, Fibrinolytic agent, medicine.drug
Abstract

Background: GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic t...

Published
2017
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4. Differential regulation of Toll-like receptor mRNAs in experimental murine central nervous system infections

Author

Ulrich Kuhnt, Uta Meyding-Lamadé, Sandra Ebert, Roland Nau, Joachim Gerber, Matthias von Mering, and Tobias Böttcher

Subjects
Meningitis, Escherichia coli, Receptors, Cell Surface, Biology, medicine.disease_cause, Hippocampus, Microbiology, 03 medical and health sciences, Central Nervous System Infections, Organ Culture Techniques, 0302 clinical medicine, medicine, Animals, RNA, Messenger, 030304 developmental biology, Regulation of gene expression, 0303 health sciences, Toll-like receptor, Membrane Glycoproteins, Innate immune system, Meningitis, Pneumococcal, Reverse Transcriptase Polymerase Chain Reaction, General Neuroscience, Toll-Like Receptors, TLR7, Toll-Like Receptor 2, Toll-Like Receptor 3, 3. Good health, Toll-Like Receptor 4, TLR2, Herpes simplex virus, Gene Expression Regulation, Toll-Like Receptor 7, TLR3, TLR4, Encephalitis, Herpes Simplex, 030217 neurology & neurosurgery
Abstract

Toll-like receptors (TLR) play a key role in the recognition of microbial components. We investigated the differential regulation of TLR mRNA expression in bacterial and viral mouse models of central nervous system infection. Streptococcus pneumoniae meningitis led to an enhanced expression of TLR2, TLR4 and TLR9 mRNA. In Escherichia coli meningitis, TLR2, TLR4 and TLR7 mRNA expression was increased and Herpes simplex encephalitis caused a rise of TLR4 mRNA. In organotypic hippocampal cultures treatment with S. pneumoniae R6 led to increased expression of TLR2 and TLR3 mRNA. Our data provide evidence that regulation of TLR mRNA is not fully specific for the molecular patterns of the infectious pathogen. The TLR mRNA regulation observed probably represents a combination of specific response to the causative pathogen and non-specific activation of the innate immune system.

Published
2003
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5. Experimental Pneumococcal Meningitis: Impaired Clearance of Bacteria from the Blood Due to Increased Apoptosis in the Spleen in Bcl-2-Deficient Mice

Author

Roland Nau, Matthias von Mering, Andreas Wellmer, Stefanie Bunkowski, Christiane Noeske, Annette Spreer, Helmut Eiffert, Ralf Gold, and Ricarda Diem

Subjects
Programmed cell death, Necrosis, Ratón, Immunology, Colony Count, Microbial, Spleen, Apoptosis, medicine.disease_cause, Microbiology, Andrology, 03 medical and health sciences, Mice, 0302 clinical medicine, Streptococcus pneumoniae, medicine, Animals, Humans, Lymphocytes, 030304 developmental biology, Mice, Knockout, 0303 health sciences, Host Response and Inflammation, biology, Meningitis, Pneumococcal, Streptococcaceae, biology.organism_classification, medicine.disease, 3. Good health, Mice, Inbred C57BL, Disease Models, Animal, Infectious Diseases, medicine.anatomical_structure, Blood, Proto-Oncogene Proteins c-bcl-2, Parasitology, medicine.symptom, Meningitis, 030217 neurology & neurosurgery
Abstract

Necrotic and apoptotic neuronal cell death can be found in pneumococcal meningitis. We investigated the role of Bcl-2 as an antiapoptotic gene product in pneumococcal meningitis using Bcl-2 knockout (Bcl-2−/−) mice. By using a model of pneumococcal meningitis induced by intracerebral infection, Bcl-2-deficient mice and control littermates were assessed by clinical score and a tight rope test at 0, 12, 24, 32, and 36 h after infection. Then mice were sacrificed, the bacterial titers in blood, spleen, and cerebellar homogenates were determined, and the brain and spleen were evaluated histologically. The Bcl-2-deficient mice developed more severe clinical illness, and there were significant differences in the clinical score at 24, 32, and 36 h and in the tight rope test at 12 and 32 h. The bacterial titers in the blood were greater in Bcl-2-deficient mice than in the controls (7.46 ± 1.93 log CFU/ml versus 5.16 ± 0.96 log CFU/ml [mean ± standard deviation];P< 0.01). Neuronal damage was most prominent in the hippocampal formation, but there were no significant differences between groups. In situ tailing revealed only a few apoptotic neurons in the brain. In the spleen, however, there were significantly more apoptotic leukocytes in Bcl-2-deficient mice than in controls (5,148 ± 3,406 leukocytes/mm2versus 1,070 ± 395 leukocytes/mm2;P< 0.005). Bcl-2 appears to counteract sepsis-induced apoptosis of splenic lymphocytes, thereby enhancing clearance of bacteria from the blood.

Published
2004

6. Decreased Virulence of a Pneumolysin-Deficient Strain of Streptococcus pneumoniae in Murine Meningitis

Author

Tammo Kunst, Matthias von Mering, Helmut Eiffert, Roland Nau, Stefanie Bunkowski, Gregor Zysk, Joachim Gerber, and Andreas Wellmer

Subjects
Immunology, Virulence, Hyaluronoglucosaminidase, Neuraminidase, Spleen, medicine.disease_cause, Microbiology, Pathogenesis, 03 medical and health sciences, Mice, Bacterial Proteins, Streptococcus pneumoniae, medicine, Animals, 030304 developmental biology, 0303 health sciences, Pneumolysin, biology, 030306 microbiology, Bacterial Infections, Pneumonia, Pneumococcal, medicine.disease, Streptococcaceae, biology.organism_classification, Virology, 3. Good health, Mice, Inbred C57BL, Infectious Diseases, medicine.anatomical_structure, Streptolysins, biology.protein, Parasitology, Meningitis
Abstract

Pneumolysin, neuraminidases A and B, and hyaluronidase are virulence factors of Streptococcus pneumoniae that appear to be involved in the pathogenesis of meningitis. In a murine model of meningitis after intracerebral infection using mutants of S. pneumoniae D39, only mice infected with a pneumolysin-deficient strain were healthier at 32 and 36 h, had lower bacterial titers in blood at 36 h, and survived longer than the D39 parent strain. Cerebellar and spleen bacterial titers, meningeal inflammation, and neuronal damage scores remained uninfluenced by the lack of any of the virulence factors.

Published
2002

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