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1. Der kardiovaskulär vorerkrankte Diabetespatient

Author: Florian Kahles and Michael Lehrke
Subjects: medicine.medical_specialty, business.industry, Internal medicine, Medicine, General Medicine, Diabetic patient, business
Published: 2021
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2. Mechanical thrombectomy using the new Tigertriever in acute ischemic stroke patients – A Swiss prospective multicenter study

Author: Timo Kahles, Luca Remonda, Michael Diepers, Jatta Berberat, Alexander von Hessling, David S Liebeskind, Krassen Nedeltchev, Philipp Gruber, Johannes Weber, and Javier Anon
Subjects: Male, medicine.medical_specialty, business.industry, Middle Aged, medicine.disease, Stroke, Mechanical thrombectomy, Multicenter study, Internal medicine, medicine, Cardiology, Feasibility Studies, Humans, Female, Patient Safety, Prospective Studies, Registries, business, Acute ischemic stroke, Switzerland, Aged, Ischemic Stroke, Thrombectomy, Large vessel occlusion
Abstract: Purpose Tigertriever is a novel operator-adjustable clot retriever designed to enhance the operator's options to control the interaction of retriever and clot. The aim of this study was to assess the feasibility, safety and efficacy of the Tigertriever device system. Methods Prospective multi-center registry study at three comprehensive stroke centers in Switzerland from 2017 to 2019 of patients with acute ischemic stroke (AIS) and large vessel occlusion (LVO) using Tigertriever as a first-line device. Results 30 AIS patients (median age 72.5 years (IQR 64–79), 50% women) with a median NIHSS on admission of 11 (IQR 6-13) and a median ASPECT score of 9 (IQR 7–10) were treated with the new Tigertriever and included in this study. The first-pass effect was 24% (n = 7). A good recanalization (eTICI 2 b/2c/3) was achieved in 94% of the cases. Median mRS at 90 days was 1 (IQR 1–2). Conclusion This study demonstrated feasibility, safety and effectiveness of the Tigertriever in AIS patients with LVO with a high reperfusion rate.
Published: 2020
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3. Biomarkers and antithrombotic treatment in cervical artery dissection – Design of the TREAT-CAD randomised trial

Author: Alex Brehm, Marcel Arnold, Christopher Traenka, Timo Kahles, Philippe Lyrer, Sabine Schaedelin, Lars Kellert, Andreas R. Luft, Christian H. Nolte, Georg Kägi, Marios Psychogios, Sverre Rosenbaum, Henrik Gensicke, Roman Sztaizel, Patrik Michel, Christoph Stippich, and Stefan T. Engelter
Subjects: medicine.medical_specialty, Cervical Artery, business.industry, CAD, Dissection (medical), 030204 cardiovascular system & hematology, medicine.disease, Surgery, 03 medical and health sciences, Antithrombotic treatment, 0302 clinical medicine, Protocol, medicine, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, Stroke, 030217 neurology & neurosurgery
Abstract: Introduction The type of antithrombotic treatment in cervical artery dissection patients is still a matter of debate. Most physicians prefer anticoagulants over antiplatelet agents for stroke prevention. However, this approach is not evidence-based and antiplatelets might be as safe and as effective. The ‘Biomarkers and Antithrombotic Treatment in Cervical Artery Dissection’ (‘TREAT-CAD’) trial (clinicaltrials.gov: NCT02046460) compares Aspirin to oral anticoagulants (vitamin K antagonists) with regard to efficacy and safety by using both clinical and imaging surrogate outcome measures. TREAT-CAD tests the hypothesis, that aspirin is as safe and effective as vitamin K antagonists. Patients and methods TREAD-CAD is a Prospective, Randomised controlled, Open-labelled, multicentre, non-inferiority trial with Blinded assessment of outcome Events (PROBE-design). Key eligibility criteria are (i) clinical symptoms attributable to cervical artery dissection and (ii) verification of the cervical artery dissection diagnosis by established magnetic resonance imaging criteria. Patients are randomised to receive either Aspirin 300 mg daily or vitamin K antagonists for 90 days. Results Primary outcomes are assessed at 14 ± 10 days (magnetic resonance imaging and clinical examination) and at 90 ± 30 days (clinical examinations). The primary endpoint is a composite outcome measure – labelled Cerebrovascular Ischemia, major Hemorrhagic events or Death (CIHD) – and includes (i) occurrence of any stroke (including retinal infarction), (ii) new ischaemic lesions on diffusion-weighted magnetic resonance imaging, (iii) any major extracranial haemorrhage, (iv) any symptomatic intracranial haemorrhage, (v) any new haemorrhagic lesion visible on paramagnetic-susceptible sequences and (vi) death. Discussion After database closure, (i) central verification of cervical artery dissection diagnosis will be done by two experienced raters, (ii) adjudication of outcome events will be performed by independent adjudication committees, separately for clinical and imaging outcomes. The primary analysis will be done on the per protocol data set. The targeted sample size consists of 169 evaluable patients in the per protocol data set. Conclusion TREAT-CAD is testing the non-inferiority of Aspirin versus vitamin K antagonists treatment in patients with symptomatic cervical artery dissection by combined clinical and magnetic resonance imaging outcomes.
Published: 2020
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4. Ischemic stroke in COVID-19 patients: Mechanisms, treatment, and outcomes in a consecutive Swiss Stroke Registry analysis

Author: Ludwig Schelosky, Valerian L Altersberger, Nils Peters, Christophe Bonvin, Marcel Arnold, Marie-Luise Mono, Stefan T. Engelter, Lehel-Barna Lakatos, Shadi Taheri, Georg Kägi, Giovanni Bianco, Santi Galletta, Andrea von Reding, Carlo W. Cereda, Emmanuel Carrera, Davide Strambo, Manuel Bolognese, Krassen Nedeltchev, Guido Schwegler, Alexander A. Tarnutzer, Florian Lindheimer, Morin Beyeler, Christian Berger, Urs Fischer, Andreas R. Luft, Rolf Sturzenegger, Biljana Rodic, Federico Massini, Gian Marco De Marchis, Leo H. Bonati, Markus Baumgärtner, Patrik Michel, Albert Sylvan, Friedrich Medlin, Pamela N Correia, Timo Kahles, Stephan Salmen, and Swiss Stroke Registry Investigators
Subjects: medicine.medical_specialty, Multivariate analysis, medicine.medical_treatment, 610 Medicine & health, Revascularization, Asymptomatic, COVID-19, Humans, Ischemic Stroke, Registries, SARS-CoV-2, Stroke/epidemiology, Stroke/therapy, Switzerland/epidemiology, Treatment Outcome, ischemic stroke, Internal medicine, medicine, Stroke, business.industry, medicine.disease, Neurology, Radiological weapon, Concomitant, Propensity score matching, Etiology, Neurology (clinical), medicine.symptom, business, 610 Medizin und Gesundheit, Switzerland
Abstract: Most case series of patients with ischemic stroke (IS) and COVID-19 are limited to selected centers or lack 3-month outcomes. The aim of this study was to describe the frequency, clinical and radiological features, and 3-month outcomes of patients with IS and COVID-19 in a nationwide stroke registry. From the Swiss Stroke Registry (SSR), we included all consecutive IS patients ≥18 years admitted to Swiss Stroke Centers or Stroke Units during the first wave of COVID-19 (25 February to 8 June 2020). We compared baseline features, etiology, and 3-month outcome of SARS-CoV-2 polymerase chain reaction-positive (PCR+) IS patients to SARS-CoV-2 PCR- and/or asymptomatic non-tested IS patients. Of the 2341 IS patients registered in the SSR during the study period, 36 (1.5%) had confirmed COVID-19 infection, of which 33 were within 1 month before or after stroke onset. In multivariate analysis, COVID+ patients had more lesions in multiple vascular territories (OR 2.35, 95% CI 1.08-5.14, p = 0.032) and fewer cryptogenic strokes (OR 0.37, 95% CI 0.14-0.99, p = 0.049). COVID-19 was judged the likely principal cause of stroke in 8 patients (24%), a contributing/triggering factor in 12 (36%), and likely not contributing to stroke in 13 patients (40%). There was a strong trend towards worse functional outcome in COVID+ patients after propensity score (PS) adjustment for age, stroke severity, and revascularization treatments (PS-adjusted common OR for shift towards higher modified Rankin Scale (mRS) = 1.85, 95% CI 0.96-3.58, p = 0.07). In this nationwide analysis of consecutive ischemic strokes, concomitant COVID-19 was relatively rare. COVID+ patients more often had multi-territory stroke and less often cryptogenic stroke, and their 3-month functional outcome tended to be worse.
Published: 2022
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5. Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

Author: Alison Halliday, Richard Bulbulia, Leo H Bonati, Johanna Chester, Andrea Cradduck-Bamford, Richard Peto, Hongchao Pan, John Potter, Hans Henning Eckstein, Barbara Farrell, Marcus Flather, Averil Mansfield, Boby Mihaylova, Kazim Rahimi, David Simpson, Dafydd Thomas, Peter Sandercock, Richard Gray, Andrew Molyneux, Cliff P Shearman, Peter Rothwell, Anna Belli, Will Herrington, Parminder Judge, Peter Leopold, Marion Mafham, Michael Gough, Piergiorgio Cao, Sumaira MacDonald, Vasha Bari, Clive Berry, S Bradshaw, Wojciech Brudlo, Alison Clarke, Robin Cox, Susan Fathers, Kamran Gaba, Mo Gray, Elizabeth Hayter, Constance Holliday, Rijo Kurien, Michael Lay, Steffi le Conte, Jessica McManus, Zahra Madgwick, Dylan Morris, Andrew Munday, Sandra Pickworth, Wiktor Ostasz, Michiel Poorthuis, Sue Richards, Louisa Teixeira, Sergey Tochlin, Lynda Tully, Carol Wallis, Monique Willet, Alan Young, Renato Casana, Chiara Malloggi, Andrea Odero Jr, Vincenzo Silani, Gianfranco Parati, Giuseppe Malchiodi, Giovanni Malferrari, Francesco Strozzi, Nicola Tusini, Enrico Vecchiati, Gioacchino Coppi, Antonio Lauricella, Roberto Moratto, Roberto Silingardi, Jessica Veronesi, Andrea Zini, Emanuele Ferrero, Michelangelo Ferri, Andrea Gaggiano, Carmelo Labate, Franco Nessi, Daniele Psacharopulo, Andrea Viazzo, Giovanni Malacrida, Daniela Mazzaccaro, Giovanni Meola, Alfredo Modafferi, Giovanni Nano, Maria Teresa Occhiuto, Paolo Righini, Silvia Stegher, Stefano Chiarandini, Filippo Griselli, Sandro Lepidi, Fabio Pozzi Mucelli, Marcello Naccarato, Mario D'Oria, Barbara Ziani, Andrea Stella, Mortalla Dieng, Gianluca Faggioli, Mauro Gargiulo, Sergio Palermo, Rodolfo Pini, Giovanni Maria Puddu, Andrea Vacirca, Domenico Angiletta, Claudio Desantis, Davide Marinazzo, Giovanni Mastrangelo, Guido Regina, Raffaele Pulli, Paolo Bianchi, Lea Cireni, Elisabetta Coppi, Rocco Pizzirusso, Filippo Scalise, Giovanni Sorropago, Valerio Tolva, Valeria Caso, Enrico Cieri, Paola DeRango, Luca Farchioni, Giacomo Isernia, Massimo Lenti, Gian Battista Parlani, Guglielmo Pupo, Grazia Pula, Gioele Simonte, Fabio Verzini, Federico Carimati, Maria Luisa Delodovici, Federico Fontana, Gabriele Piffaretti, Matteo Tozzi, Efrem Civilini, Giorgio Poletto, Bernhard Reimers, Barbara Praquin, Sonia Ronchey, Laura Capoccia, Wassim Mansour, Enrico Sbarigia, Francesco Speziale, Pasqualino Sirignano, Danilo Toni, Roberto Galeotti, Vincenzo Gasbarro, Francesco Mascoli, Tiberio Rocca, Elpiniki Tsolaki, Giulia Bernardini, Ester DeMarco, Alessia Giaquinta, Francesco Patti, Massimiliano Veroux, Pierfrancesco Veroux, Carla Virgilio, Nicola Mangialardi, Matteo Orrico, Vincenzo Di Lazzaro, Nunzio Montelione, Francesco Spinelli, Francesco Stilo, Carlo Cernetti, Sandro Irsara, Giuseppe Maccarrone, Diego Tonello, Adriana Visonà, Beniamino Zalunardo, Emiliano Chisci, Stefano Michelagnoli, Nicola Troisi, Maela Masato, Massimo Dei Negri, Andrea Pacchioni, Salvatore Saccà, Giovanni Amatucci, Alfredo Cannizzaro, Federico Accrocca, Cesare Ambrogi, Renzo Barbazza, Giustino Marcucci, Andrea Siani, Guido Bajardi, Giovanni Savettieri, Angelo Argentieri, Riccardo Corbetta, Attilio Odero, Pietro Quaretti, Federico Z Thyrion, Alessandro Cappelli, Domenico Benevento, Gianmarco De Donato, Maria Agnese Mele, Giancarlo Palasciano, Daniela Pieragalli, Alessandro Rossi, Carlo Setacci, Francesco Setacci, Domenico Palombo, Maria Cecilia Perfumo, Edoardo Martelli, Aldo Paolucci, Santi Trimarchi, Viviana Grassi, Luigi Grimaldi, Giuliana La Rosa, Domenico Mirabella, Matteo Scialabba, Leonildo Sichel, Costantino L D'Angelo, Gian Franco Fadda, Holta Kasemi, Mario Marino, Francesco Burzotta, Francesco Alberto Codispoti, Angela Ferrante, Giovanni Tinelli, Yamume Tshomba, Claudio Vincenzoni, Deborah Amis, Dawn Anderson, Martin Catterson, Mike Clarke, Michelle Davis, Anand Dixit, Alexander Dyker, Gary Ford, Ralph Jackson, Sreevalsan Kappadath, David Lambert, Tim Lees, Stephen Louw, James McCaslin, Noala Parr, Rebecca Robson, Gerard Stansby, Lucy Wales, Vera Wealleans, Lesley Wilson, Michael Wyatt, Hardeep Baht, Ibrahim Balogun, Ilse Burger, Tracy Cosier, Linda Cowie, Gunaratnam Gunathilagan, David Hargroves, Robert Insall, Sally Jones, Hannah Rudenko, Natasha Schumacher, Jawaharlal Senaratne, George Thomas, Audrey Thomson, Tom Webb, Ellen Brown, Bernard Esisi, Ali Mehrzad, Shane MacSweeney, Norman McConachie, Alison Southam, Wayne Sunman, Ahmed Abdul-Hamiq, Jenny Bryce, Ian Chetter, Duncan Ettles, Raghuram Lakshminarayan, Kim Mitchelson, Christopher Rhymes, Graham Robinson, Paul Scott, Alison Vickers, Ray Ashleigh, Stephen Butterfield, Ed Gamble, Jonathan Ghosh, Charles N McCollum, Mark Welch, Sarah Welsh, Leszek Wolowczyk, Mary Donnelly, Stephen D'Souza, Anselm A Egun, Bindu Gregary, Thomas Joseph, Christine Kelly, Shuja Punekar, M Asad Rahi, Sonia Raj, Dare Seriki, George Thomson, James Brown, Ragunath Durairajan, Iris Grunwald, Paul Guyler, Paula Harman, Matthew Jakeways, Christopher Khuoge, Ashish Kundu, Thayalini Loganathan, Nisha Menon, Raji O Prabakaran, Devesh Sinha, Vicky Thompson, Sharon Tysoe, Dennis Briley, Chris Darby, Linda Hands, Dominic Howard, Wilhelm Kuker, Ursula Schulz, Rachel Teal, David Barer, Andrew Brown, Susan Crawford, Paul Dunlop, Ramesh Krishnamurthy, Nikhil Majmudar, Duncan Mitchell, Min P Myint, Richard O'Brien, Janice O'Connell, Naweed Sattar, Shanmugam Vetrivel, Jonathan Beard, Trevor Cleveland, Peter Gaines, John Humphreys, Alison Jenkins, Craig King, Daniel Kusuma, Ralph Lindert, Robbie Lonsdale, Raj Nair, Shah Nawaz, Faith Okhuoya, Douglas Turner, Graham Venables, Paul Dorman, Andrea Hughes, Deborah Jones, David Mendelow, Helen Rodgers, Aidas Raudoniitis, Peter Enevoldson, Hans Nahser, Imelda O'Brien, Francesco Torella, Dave Watling, Richard White, Pauline Brown, Dipankar Dutta, Lorraine Emerson, Paula Hilltout, Sachin Kulkarni, Jackie Morrison, Keith Poskitt, Fiona Slim, Sarah Smith, Amanda Tyler, Joanne Waldron, Mark Whyman, Milda Bajoriene, Lucy Baker, Amanda Colston, Bekky Eliot-Jones, Gita Gramizadeh, Catherine Lewis-Clarke, Laura McCafferty, Deborah Oliver, Debbie Palmer, Abhijeet Patil, Suzannah Pegler, Gopi Ramadurai, Aisling Roberts, Tracey Sargent, Shivaprasad Siddegowda, Ravi Singh-Ranger, Akintunde Williams, Lucy Williams, Steve Windebank, Tadas Zuromskis, Lanka Alwis, Jane Angus, Asaipillai Asokanathan, Caroline Fornolles, Diana Hardy, Sophy Hunte, Frances Justin, Duke Phiri, Marie Mitabouana-Kibou, Lakshmanan Sekaran, Sakthivel Sethuraman, Margaret L Tate, Joyce Akyea-Mensah, Stephen Ball, Angela Chrisopoulou, Elizabeth Keene, Alison Phair, Steven Rogers, John V Smyth, Colin Bicknell, Jeremy Chataway, Nicholas Cheshire, Andrew Clifton, Caroline Eley, Richard Gibbs, Mohammad Hamady, Beth Hazel, Alex James, Michael Jenkins, Nyma Khanom, Austin Lacey, Maz Mireskandari, Joanna O'Reilly, Antony Pereira, Tina Sachs, John Wolfe, Philip Davey, Gill Rogers, Gemma Smith, Gareth Tervit, Ian Nichol, Andrew Parry, Gavin Young, Simon Ashley, James Barwell, Francis Dix, Azlisham M Nor, Chris Parry, Angela Birt, Paul Davies, Jim George, Anne Graham, Leon Jonker, Nicci Kelsall, Caroline Potts, Toni Wilson, Jamie Crinnion, Larissa Cuenoud, Nikola Aleksic, Srdan Babic, Nenad Ilijevski, Đorde Radak, Dragan Sagic, Slobodan Tanaskovic, Momcilo Colic, Vladimir Cvetic, Lazar Davidovic, Dejana R Jovanovic, Igor Koncar, Perica Mutavdžic, Miloš Sladojevic, Ivan Tomic, Eike S Debus, Ulrich Grzyska, Dagmar Otto, Götz Thomalla, Jessica Barlinn, Johannes Gerber, Kathrin Haase, Christian Hartmann, Stefan Ludwig, Volker Pütz, Christian Reeps, Christine Schmidt, Norbert Weiss, Sebastian Werth, Simon Winzer, Janine Gemper, Albrecht Günther, Bianka Heiling, Elisabeth Jochmann, Panagiota Karvouniari, Carsten Klingner, Thomas Mayer, Julia Schubert, Friederike Schulze-Hartung, Jürgen Zanow, Yvonne Bausback, Franka Borger, Spiridon Botsios, Daniela Branzan, Sven Bräunlich, Henryk Hölzer, Janin Lenzer, Christopher Piorkowski, Nadine Richter, Johannes Schuster, Dierk Scheinert, Andrej Schmidt, Holger Staab, Matthias Ulrich, Martin Werner, Hermann Berger, Gábor Biró, Hans-Henning Eckstein, Michael Kallmayer, Kornelia Kreiser, Alexander Zimmermann, Bärbel Berekoven, Klaus Frerker, Vera Gordon, Giovanni Torsello, Sebastian Arnold, Cora Dienel, Martin Storck, Bernhard Biermaier, Hans Martin Gissler, Christof Klötzsch, Tomas Pfeiffer, Ralph Schneider, Leander Söhl, Michael Wennrich, Angelika Alonso, Michael Keese, Christoph Groden, Andreas Cöster, Andreas Engelhardt, Christoph-Maria Ratusinski, Bengt Berg, Martin Delle, Johan Formgren, Peter Gillgren, Lotta Jarl, Torbjörn B Kall, Peter Konrad, Niklas Nyman, Claes Skiöldebrand, Johnny Steuer, Rabbe Takolander, Jonas Malmstedt, Stefan Acosta, Katarina Björses, Kerstin Brandt, Nuno Dias, Anders Gottsäter, Jan Holst, Thorarinn Kristmundsson, Tobias Kühme, Tilo Kölbel, Bengt Lindblad, Mats Lindh, Martin Malina, Tomas Ohrlander, Tim Resch, Viola Rönnle, Björn Sonesson, Margareta Warvsten, Zbigniew Zdanowski, Erik Campbell, Per Kjellin, Hans Lindgren, Johan Nyberg, Björn Petersen, Gunnar Plate, Håkan Pärsson, Peter Qvarfordt, Pavel Ignatenko, Andrey Karpenko, Vladimir Starodubtsev, Mikhail A Chernyavsky, Maria S Golovkova, Boris B Komakha, Nikolay N Zherdev, Andrey Belyasnik, Pavel Chechulov, Dmitry Kandyba, Igor Stepanishchev, Csaba Csobay-Novák, Edit Dósa, László Entz, Balázs Nemes, Zoltán Szeberin, Pál Barzó, Mihaly Bodosi, Eniko Fákó, Béla Fülöp, Tamás Németh, Szilárd Pazdernyik, Krisztina Skoba, Erika Vörös, Eleni Chatzinikou, Athanasios Giannoukas, Christos Karathanos, Stylianos Koutsias, Georgios Kouvelos, Miltiadis Matsagkas, Styliani Ralli, Christos Rountas, Nikolaos Rousas, Konstantinos Spanos, Elias Brountzos, John D Kakisis, Andreas Lazaris, Konstantinos G Moulakakis, Leonidas Stefanis, Georgios Tsivgoulis, Spyros Vasdekis, Constantine N Antonopoulos, Ion Bellenis, Dimitrios Maras, Antonios Polydorou, Victoria Polydorou, Antonios Tavernarakis, Nikolaos Ioannou, Maria Terzoudi, Miltos Lazarides, Michalis Mantatzis, Kostas Vadikolias, Lukasz Dzieciuchowicz, Marcin Gabriel, Zbigniew Krasinski, Grzegorz Oszkinis, Fryderyk Pukacki, Maciej Slowinski, Michal-Goran Stanišic, Ryszard Staniszewski, Jolanta Tomczak, Maciej Zielinski, Piotr Myrcha, Dorota Rózanski, Stanislaw Drelichowski, Wojciech Iwanowski, Katarzyna Koncewicz, Pawel Bialek, Zbigniew Biejat, Wojciech Czepel, Anna Czlonkowska, Anatol Dowzenko, Julia Jedrzejewska, Adam Kobayashi, Jerzy Leszczynski, Andrzej Malek, Jerzy Polanski, Robert Proczka, Maciej Skorski, Mieczyslaw Szostek, Piotr Andziak, Maciej Dratwicki, Robert Gil, Miroslaw Nowicki, Jaroslaw Pniewski, Jaroslaw Rzezak, Piotr Seweryniak, Pawel Dabek, Michal Juszynski, Grzegorz Madycki, Bartosz Pacewski, Witold Raciborski, Piotr Slowinski, Walerian Staszkiewicz, Martin Bombic, Vladimír Chlouba, Jirí Fiedler, Karel Hes, Petr Koštál, Jindrich Sova, Zdenek Kríž, Mojmír Prívara, Michal Reif, Robert Staffa, Robert Vlachovský, Bohuslav Vojtíšek, Tomáš Hrbác, Martin Kuliha, Václav Procházka, Martin Roubec, David Školoudík, David Netuka, Anna Šteklácová, Vladimír Beneš III, Pavel Buchvald, Ladislav Endrych, Miroslav Šercl, Walter Campos Jr, Ivan B Casella, Nelson de Luccia, André E V Estenssoro, Calógero Presti, Pedro Puech-Leão, Celso R B Neves, Erasmo S da Silva, Cid J Sitrângulo Jr, José A T Monteiro, Gisela Tinone, Marcelo Bellini Dalio, Edwaldo E Joviliano, Octávio M Pontes Neto, Mauricio Serra Ribeiro, Patrick Cras, Jeroen M H Hendriks, Mieke Hoppenbrouwers, Patrick Lauwers, Caroline Loos, Laetitia Yperzeele, Mia Geenens, Dimitri Hemelsoet, Isabelle van Herzeele, Frank Vermassen, Parla Astarci, Frank Hammer, Valérie Lacroix, André Peeters, Robert Verhelst, Silvana Cirelli, Pol Dormal, Annelies Grimonprez, Bart Lambrecht, Philipe Lerut, Eddy Thues, Guy De Koster, Quentin Desiron, Alain Maertens de Noordhout, Danielle Malmendier, Mireille Massoz, Georges Saad, Marc Bosiers, Joren Callaert, Koen Deloose, Estrella Blanco Cañibano, Beatriz García Fresnillo, Mercedes Guerra Requena, Pilar C Morata Barrado, Miguel Muela Méndez, Antonio Yusta Izquierdo, Fernando Aparici Robles, Paula Blanes Orti, Luis García Dominguez, Rafael Martínez López, Manuel Miralles Hernández, José I Tembl Ferrairo, Ángel Chamorro, Juan Macho, Víctor Obach, Vincent Riambau, Luis San Román, Frank J Ahlhelm, Kristine Blackham, Stefan Engelter, Thomas Eugster, Henrik Gensicke, Lorenz Gürke, Philippe Lyrer, Luigi Mariani, Marina Maurer, Edin Mujagic, Mandy Müller, Marios Psychogios, Peter Stierli, Christoph Stippich, Christopher Traenka, Thomas Wolff, Benjamin Wagner, Martina M Wiegert, Sandra Clarke, Michael Diepers, Ernst Gröchenig, Philipp Gruber, Andrej Isaak, Timo Kahles, Regula Marti, Krassen Nedeltchev, Luca Remonda, Nadir Tissira, Martina Valença Falcão, Gert J de Borst, Rob H Lo, Frans L Moll, Raechel Toorop, Bart H van der Worp, Evert J Vonken, Jaap L Kappelle, Ommid Jahrome, Floris Vos, Wouter Schuiling, Hendrik van Overhagen, Rudolf W M Keunen, Bob Knippenberg, Jan J Wever, Jan W Lardenoije, Michel Reijnen, Luuk Smeets, Steven van Sterkenburg, Gustav Fraedrich, Elke Gizewski, Ingrid Gruber, Michael Knoflach, Stefan Kiechl, Barbara Rantner, Timur Abdulamit, Patrice Bergeron, Raymond Padovani, Jean-Christophe Trastour, Jean-Marie Cardon, Anne Le Gallou-Wittenberg, Eric Allaire, Jean-Pierre Becquemin, Frédéric Cochennec-Paliwoda, Pascal Desgranges, Hassan Hosseini, Hicham Kobeiter, Jean Marzelle, Mohammed A Almekhlafi, Simerpreet Bal, Phillip A Barber, Shelagh B Coutts, Andrew M Demchuk, Muneer Eesa, Michelle Gillies, Mayank Goyal, Michael D Hill, Mark E Hudon, Anitha Jambula, Carol Kenney, Gary Klein, Marie McClelland, Alim Mitha, Bijoy K Menon, William F Morrish, Steven Peters, Karla J Ryckborst, Greg Samis, Supriya Save, Eric E Smith, Peter Stys, Suresh Subramaniam, Garnette R Sutherland, Tim Watson, John H Wong, L Zimmel, Vojko Flis, Jože Matela, Kazimir Miksic, Franko Milotic, Božidar Mrdja, Barbara Stirn, Erih Tetickovic, Mladen Gasparini, Anton Grad, Ingrid Kompara, Zoren Miloševic, Veronika Palmiste, Toomas Toomsoo, Balzhan Aidashova, Nursultan Kospanov, Roman Lyssenko, Daulet Mussagaliev, Rafi Beyar, Aaron Hoffman, Tony Karram, Arthur Kerner, Eugenia Nikolsky, Samy Nitecki, Silva Andonova, Chavdar Bachvarov, Vesko Petrov, Ivan Cvjetko, Vinko Vidjak, Damir Halužan, Mladen Petrunic, Bao Liu, Chang-Wei Liu, Daniel Bartko, Peter Beno, František Rusnák, Kamil Zelenák, Masayuki Ezura, Takashi Inoue, Naoto Kimura, Ryushi Kondo, Yasushi Matsumoto, Hiroaki Shimizu, Hidenori Endo, Eisuke Furui, Søren Bakke, Kristen Krohg-Sørensen, Terje Nome, Mona Skjelland, Bjørn Tennøe, João Albuquerque e Castro, Gonçalo Alves, Frederico Bastos Gonçalves, José de Aragão Morais, Ana C Garcia, Hugo Valentim, Leonor Vasconcelos, Fernando Belcastro, Fernando Cura, Patricio Zaefferer, Foad Abd-Allah, Mohamed H Eldessoki, Hussein Heshmat Kassem, Haytham Soliman Gharieb, Mary P Colgan, Syed N Haider, Joe Harbison, Prakash Madhavan, Dermot Moore, Gregor Shanik, Viviane Kazan, Munier Nazzal, Vicki Ramsey-Williams, ACST-2 Collaborative Group, Group, ACST-2 Collaborative, Halliday A., Bulbulia R., Bonati L.H., Chester J., Cradduck-Bamford A., Peto R., Pan H., Potter J., Henning Eckstein H., Farrell B., Flather M., Mansfield A., Mihaylova B., Rahimi K., Simpson D., Thomas D., Sandercock P., Gray R., Molyneux A., Shearman C.P., Rothwell P., Belli A., Herrington W., Judge P., Leopold P., Mafham M., Gough M., Cao P., MacDonald S., Bari V., Berry C., Bradshaw S., Brudlo W., Clarke A., Cox R., Fathers S., Gaba K., Gray M., Hayter E., Holliday C., Kurien R., Lay M., le Conte S., McManus J., Madgwick Z., Morris D., Munday A., Pickworth S., Ostasz W., Poorthuis M., Richards S., Teixeira L., Tochlin S., Tully L., Wallis C., Willet M., Young A., Casana R., Malloggi C., Odero A., Silani V., Parati G., Malchiodi G., Malferrari G., Strozzi F., Tusini N., Vecchiati E., Coppi G., Lauricella A., Moratto R., Silingardi R., Veronesi J., Zini A., Ferrero E., Ferri M., Gaggiano A., Labate C., Nessi F., Psacharopulo D., Viazzo A., Malacrida G., Mazzaccaro D., Meola G., Modafferi A., Nano G., Occhiuto M.T., Righini P., Stegher S., Chiarandini S., Griselli F., Lepidi S., Pozzi Mucelli F., Naccarato M., D'Oria M., Ziani B., Stella A., Dieng M., Faggioli G., Gargiulo M., Palermo S., Pini R., Puddu G.M., Vacirca A., Angiletta D., Desantis C., Marinazzo D., Mastrangelo G., Regina G., Pulli R., Bianchi P., Cireni L., Coppi E., Pizzirusso R., Scalise F., Sorropago G., Tolva V., Caso V., Cieri E., DeRango P., Farchioni L., Isernia G., Lenti M., Parlani G.B., Pupo G., Pula G., Simonte G., Verzini F., Carimati F., Delodovici M.L., Fontana F., Piffaretti G., Tozzi M., Civilini E., Poletto G., Reimers B., Praquin B., Ronchey S., Capoccia L., Mansour W., Sbarigia E., Speziale F., Sirignano P., Toni D., Galeotti R., Gasbarro V., Mascoli F., Rocca T., Tsolaki E., Bernardini G., DeMarco E., Giaquinta A., Patti F., Veroux M., Veroux P., Virgilio C., Mangialardi N., Orrico M., Di Lazzaro V., Montelione N., Spinelli F., Stilo F., Cernetti C., Irsara S., Maccarrone G., Tonello D., Visona A., Zalunardo B., Chisci E., Michelagnoli S., Troisi N., Masato M., Dei Negri M., Pacchioni A., Sacca S., Amatucci G., Cannizzaro A., Accrocca F., Ambrogi C., Barbazza R., Marcucci G., Siani A., Bajardi G., Savettieri G., Argentieri A., Corbetta R., Quaretti P., Thyrion F.Z., Cappelli A., Benevento D., De Donato G., Mele M.A., Palasciano G., Pieragalli D., Rossi A., Setacci C., Setacci F., Palombo D., Perfumo M.C., Martelli E., Paolucci A., Trimarchi S., Grassi V., Grimaldi L., La Rosa G., Mirabella D., Scialabba M., Sichel L., D'Angelo C.L., Fadda G.F., Kasemi H., Marino M., Burzotta F., Codispoti F.A., Ferrante A., Tinelli G., Tshomba Y., Vincenzoni C., Amis D., Anderson D., Catterson M., Clarke M., Davis M., Dixit A., Dyker A., Ford G., Jackson R., Kappadath S., Lambert D., Lees T., Louw S., McCaslin J., Parr N., Robson R., Stansby G., Wales L., Wealleans V., Wilson L., Wyatt M., Baht H., Balogun I., Burger I., Cosier T., Cowie L., Gunathilagan G., Hargroves D., Insall R., Jones S., Rudenko H., Schumacher N., Senaratne J., Thomas G., Thomson A., Webb T., Brown E., Esisi B., Mehrzad A., MacSweeney S., McConachie N., Southam A., Sunman W., Abdul-Hamiq A., Bryce J., Chetter I., Ettles D., Lakshminarayan R., Mitchelson K., Rhymes C., Robinson G., Scott P., Vickers A., Ashleigh R., Butterfield S., Gamble E., Ghosh J., McCollum C.N., Welch M., Welsh S., Wolowczyk L., Donnelly M., D'Souza S., Egun A.A., Gregary B., Joseph T., Kelly C., Punekar S., Rahi M.A., Raj S., Seriki D., Thomson G., Brown J., Durairajan R., Grunwald I., Guyler P., Harman P., Jakeways M., Khuoge C., Kundu A., Loganathan T., Menon N., Prabakaran R.O., Sinha D., Thompson V., Tysoe S., Briley D., Darby C., Hands L., Howard D., Kuker W., Schulz U., Teal R., Barer D., Brown A., Crawford S., Dunlop P., Krishnamurthy R., Majmudar N., Mitchell D., Myint M.P., O'Brien R., O'Connell J., Sattar N., Vetrivel S., Beard J., Cleveland T., Gaines P., Humphreys J., Jenkins A., King C., Kusuma D., Lindert R., Lonsdale R., Nair R., Nawaz S., Okhuoya F., Turner D., Venables G., Dorman P., Hughes A., Jones D., Mendelow D., Rodgers H., Raudoniitis A., Enevoldson P., Nahser H., O'Brien I., Torella F., Watling D., White R., Brown P., Dutta D., Emerson L., Hilltout P., Kulkarni S., Morrison J., Poskitt K., Slim F., Smith S., Tyler A., Waldron J., Whyman M., Bajoriene M., Baker L., Colston A., Eliot-Jones B., Gramizadeh G., Lewis-Clarke C., McCafferty L., Oliver D., Palmer D., Patil A., Pegler S., Ramadurai G., Roberts A., Sargent T., Siddegowda S., Singh-Ranger R., Williams A., Williams L., Windebank S., Zuromskis T., Alwis L., Angus J., Asokanathan A., Fornolles C., Hardy D., Hunte S., Justin F., Phiri D., Mitabouana-Kibou M., Sekaran L., Sethuraman S., Tate M.L., Akyea-Mensah J., Ball S., Chrisopoulou A., Keene E., Phair A., Rogers S., Smyth J.V., Bicknell C., Chataway J., Cheshire N., Clifton A., Eley C., Gibbs R., Hamady M., Hazel B., James A., Jenkins M., Khanom N., Lacey A., Mireskandari M., O'Reilly J., Pereira A., Sachs T., Wolfe J., Davey P., Rogers G., Smith G., Tervit G., Nichol I., Parry A., Young G., Ashley S., Barwell J., Dix F., Nor A.M., Parry C., Birt A., Davies P., George J., Graham A., Jonker L., Kelsall N., Potts C., Wilson T., Crinnion J., Cuenoud L., Aleksic N., Babic S., Ilijevski N., Radak, Sagic D., Tanaskovic S., Colic M., Cvetic V., Davidovic L., Jovanovic D.R., Koncar I., Mutavdzic P., Sladojevic M., Tomic I., Debus E.S., Grzyska U., Otto D., Thomalla G., Barlinn J., Gerber J., Haase K., Hartmann C., Ludwig S., Putz V., Reeps C., Schmidt C., Weiss N., Werth S., Winzer S., Gemper J., Gunther A., Heiling B., Jochmann E., Karvouniari P., Klingner C., Mayer T., Schubert J., Schulze-Hartung F., Zanow J., Bausback Y., Borger F., Botsios S., Branzan D., Braunlich S., Holzer H., Lenzer J., Piorkowski C., Richter N., Schuster J., Scheinert D., Schmidt A., Staab H., Ulrich M., Werner M., Berger H., Biro G., Eckstein H.-H., Kallmayer M., Kreiser K., Zimmermann A., Berekoven B., Frerker K., Gordon V., Torsello G., Arnold S., Dienel C., Storck M., Biermaier B., Gissler H.M., Klotzsch C., Pfeiffer T., Schneider R., Sohl L., Wennrich M., Alonso A., Keese M., Groden C., Coster A., Engelhardt A., Ratusinski C.-M., Berg B., Delle M., Formgren J., Gillgren P., Jarl L., Kall T.B., Konrad P., Nyman N., Skioldebrand C., Steuer J., Takolander R., Malmstedt J., Acosta S., Bjorses K., Brandt K., Dias N., Gottsater A., Holst J., Kristmundsson T., Kuhme T., Kolbel T., Lindblad B., Lindh M., Malina M., Ohrlander T., Resch T., Ronnle V., Sonesson B., Warvsten M., Zdanowski Z., Campbell E., Kjellin P., Lindgren H., Nyberg J., Petersen B., Plate G., Parsson H., Qvarfordt P., Ignatenko P., Karpenko A., Starodubtsev V., Chernyavsky M.A., Golovkova M.S., Komakha B.B., Zherdev N.N., Belyasnik A., Chechulov P., Kandyba D., Stepanishchev I., Csobay-Novak C., Dosa E., Entz L., Nemes B., Szeberin Z., Barzo P., Bodosi M., Fako E., Fulop B., Nemeth T., Pazdernyik S., Skoba K., Voros E., Chatzinikou E., Giannoukas A., Karathanos C., Koutsias S., Kouvelos G., Matsagkas M., Ralli S., Rountas C., Rousas N., Spanos K., Brountzos E., Kakisis J.D., Lazaris A., Moulakakis K.G., Stefanis L., Tsivgoulis G., Vasdekis S., Antonopoulos C.N., Bellenis I., Maras D., Polydorou A., Polydorou V., Tavernarakis A., Ioannou N., Terzoudi M., Lazarides M., Mantatzis M., Vadikolias K., Dzieciuchowicz L., Gabriel M., Krasinski Z., Oszkinis G., Pukacki F., Slowinski M., Stanisic M.-G., Staniszewski R., Tomczak J., Zielinski M., Myrcha P., Rozanski D., Drelichowski S., Iwanowski W., Koncewicz K., Bialek P., Biejat Z., Czepel W., Czlonkowska A., Dowzenko A., Jedrzejewska J., Kobayashi A., Leszczynski J., Malek A., Polanski J., Proczka R., Skorski M., Szostek M., Andziak P., Dratwicki M., Gil R., Nowicki M., Pniewski J., Rzezak J., Seweryniak P., Dabek P., Juszynski M., Madycki G., Pacewski B., Raciborski W., Slowinski P., Staszkiewicz W., Bombic M., Chlouba V., Fiedler J., Hes K., Kostal P., Sova J., Kriz Z., Privara M., Reif M., Staffa R., Vlachovsky R., Vojtisek B., Hrbac T., Kuliha M., Prochazka V., Roubec M., Skoloudik D., Netuka D., Steklacova A., Benes III V., Buchvald P., Endrych L., Sercl M., Campos W., Casella I.B., de Luccia N., Estenssoro A.E.V., Presti C., Puech-Leao P., Neves C.R.B., da Silva E.S., Sitrangulo C.J., Monteiro J.A.T., Tinone G., Bellini Dalio M., Joviliano E.E., Pontes Neto O.M., Serra Ribeiro M., Cras P., Hendriks J.M.H., Hoppenbrouwers M., Lauwers P., Loos C., Yperzeele L., Geenens M., Hemelsoet D., van Herzeele I., Vermassen F., Astarci P., Hammer F., Lacroix V., Peeters A., Verhelst R., Cirelli S., Dormal P., Grimonprez A., Lambrecht B., Lerut P., Thues E., De Koster G., Desiron Q., Maertens de Noordhout A., Malmendier D., Massoz M., Saad G., Bosiers M., Callaert J., Deloose K., Blanco Canibano E., Garcia Fresnillo B., Guerra Requena M., Morata Barrado P.C., Muela Mendez M., Yusta Izquierdo A., Aparici Robles F., Blanes Orti P., Garcia Dominguez L., Martinez Lopez R., Miralles Hernandez M., Tembl Ferrairo J.I., Chamorro A., Macho J., Obach V., Riambau V., San Roman L., Ahlhelm F.J., Blackham K., Engelter S., Eugster T., Gensicke H., Gurke L., Lyrer P., Mariani L., Maurer M., Mujagic E., Muller M., Psychogios M., Stierli P., Stippich C., Traenka C., Wolff T., Wagner B., Wiegert M.M., Clarke S., Diepers M., Grochenig E., Gruber P., Isaak A., Kahles T., Marti R., Nedeltchev K., Remonda L., Tissira N., Valenca Falcao M., de Borst G.J., Lo R.H., Moll F.L., Toorop R., van der Worp B.H., Vonken E.J., Kappelle J.L., Jahrome O., Vos F., Schuiling W., van Overhagen H., Keunen R.W.M., Knippenberg B., Wever J.J., Lardenoije J.W., Reijnen M., Smeets L., van Sterkenburg S., Fraedrich G., Gizewski E., Gruber I., Knoflach M., Kiechl S., Rantner B., Abdulamit T., Bergeron P., Padovani R., Trastour J.-C., Cardon J.-M., Le Gallou-Wittenberg A., Allaire E., Becquemin J.-P., Cochennec-Paliwoda F., Desgranges P., Hosseini H., Kobeiter H., Marzelle J., Almekhlafi M.A., Bal S., Barber P.A., Coutts S.B., Demchuk A.M., Eesa M., Gillies M., Goyal M., Hill M.D., Hudon M.E., Jambula A., Kenney C., Klein G., McClelland M., Mitha A., Menon B.K., Morrish W.F., Peters S., Ryckborst K.J., Samis G., Save S., Smith E.E., Stys P., Subramaniam S., Sutherland G.R., Watson T., Wong J.H., Zimmel L., Flis V., Matela J., Miksic K., Milotic F., Mrdja B., Stirn B., Tetickovic E., Gasparini M., Grad A., Kompara I., Milosevic Z., Palmiste V., Toomsoo T., Aidashova B., Kospanov N., Lyssenko R., Mussagaliev D., Beyar R., Hoffman A., Karram T., Kerner A., Nikolsky E., Nitecki S., Andonova S., Bachvarov C., Petrov V., Cvjetko I., Vidjak V., Haluzan D., Petrunic M., Liu B., Liu C.-W., Bartko D., Beno P., Rusnak F., Zelenak K., Ezura M., Inoue T., Kimura N., Kondo R., Matsumoto Y., Shimizu H., Endo H., Furui E., Bakke S., Krohg-Sorensen K., Nome T., Skjelland M., Tennoe B., Albuquerque e Castro J., Alves G., Bastos Goncalves F., de Aragao Morais J., Garcia A.C., Valentim H., Vasconcelos L., Belcastro F., Cura F., Zaefferer P., Abd-Allah F., Eldessoki M.H., Heshmat Kassem H., Soliman Gharieb H., Colgan M.P., Haider S.N., Harbison J., Madhavan P., Moore D., Shanik G., Kazan V., Nazzal M., Ramsey-Williams V., and Gargiulo M
Subjects: Male, medicine.medical_specialty, Time Factors, Time Factor, medicine.medical_treatment, Carotid Stenosi, MEDLINE, Carotid endarterectomy, Rate ratio, Risk Assessment, Asymptomatic, law.invention, Randomized controlled trial, law, Risk Factors, carotid artery stenting (CAS), carotid endarterectomy (CEA), Stent, medicine, Humans, Carotid Stenosis, Stroke, Endarterectomy, Aged, Endarterectomy, Carotid, business.industry, carotid artery, Risk Factor, Articles, General Medicine, trial, medicine.disease, Settore MED/22 - CHIRURGIA VASCOLARE, Surgery, Stenosis, Treatment Outcome, Settore MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE, Female, Stents, Human medicine, medicine.symptom, business, Human
Abstract: Summary Background Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding UK Medical Research Council and Health Technology Assessment Programme.
Published: 2021

6. Clustering Unknown IoT Devices in a 5G Mobile Network Security Context via Machine Learning

Author: Julen Kahles, Tony Hämmäinen, Department of Industrial Engineering and Management, Ericsson Finland, Aalto-yliopisto, and Aalto University
Subjects: business.industry, Computer science, Human–computer interaction, Context (language use), Mobile network security, Internet of Things, business, Cluster analysis, 5G
Abstract: We propose a novel machine-learning pipeline for clustering unknown IoT devices in an industrial 5G mobile-network setting. Organizing IoT devices as few homogeneous device groups improves the applicability of network-intrusion detection systems. More specifically, we develop feature engineering methods that transform IP-flows into device-level data points, define distance metrics between the data points, and apply the DBSCAN algorithm on them. Our experiments on a simulated IoT device network with varying levels of noise show that our proposed methodology outperforms alternative methods and is the only one producing a robust grouping of the IoT devices with noise present in the traffic data.
Published: 2021
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7. The gut hormone GIP predicts CV prognosis in patients with acute myocardial infarction

Author: Hugo A. Katus, Moritz Biener, M C Arrivas, Nikolaus Marx, Evangelos Giannitsis, Julia Moellmann, M V Rueckbeil, R W Mertens, Florian Kahles, and Michael Lehrke
Subjects: endocrine system, medicine.medical_specialty, business.industry, Enteroendocrine cell, medicine.disease, Glucagon-like peptide-1, Gastric inhibitory polypeptide, Endocrinology, Diabetes mellitus, Internal medicine, Hospital admission, Medicine, In patient, Myocardial infarction, Cardiology and Cardiovascular Medicine, business, hormones, hormone substitutes, and hormone antagonists, Hormone
Abstract: Background The gut incretin hormones GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide) are secreted by enteroendocrine cells following food intake leading to insulin secretion and glucose lowering. Beyond its regulatory effects in glucose metabolism activation of the GLP-1 receptor has been found to improve cardiovascular prognosis in patients with diabetes and high cardiovascular risk. The functional relevance of GIP (the other main incretin) in patients with cardiovascular disease is largely unknown. The aim of this study was to assess the predictive capacity of GIP serum levels for cardiovascular outcome in patients with acute myocardial infarction. Methods and results We investigated the predictive value of GIP serum levels at the time of hospital admission for cardiovascular prognosis in a cohort of 852 patients (67±13 years; 73% men) with acute myocardial infarction (34% STEMI, 66% NSTEMI). Kaplan-Meier curves (GIP median; cut-off: 69 pg/mL) and univariable Cox regression analyses showed that lower GIP levels were associated with an increased cardiovascular mortality (HR of logarithmized GIP values: 0.520; 95% CI: 0.30–0.90; p=0.020). After adjustment for age, sex, smoking, hypertension, hypercholesterolemia, diabetes and family history of cardiovascular disease the association between GIP levels and cardiovascular mortality remained significant with similar hazard ratios as in the univariable Cox regression model. Conclusion In summary, we found lower GIP levels to independently predict a poor cardiovascular outcome in high-risk patients with acute myocardial infarction. Future larger studies are needed to foster our understanding of the gut - heart axis as a yet fairly neglected field of system biology and to elucidate whether the GIP system might open novel therapeutic approaches for the treatment of patients with cardiovascular disease. Funding Acknowledgement Type of funding sources: None.
Published: 2021
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8. 82-jährige Patientin mit schwerem kardiorenalen Syndrom unklarer Genese

Author: J. Burian, H. Kahles, M. Koch, L. Büllesfeld, M. Henk, and F. aus dem Siepen
Subjects: Nephrology, medicine.medical_specialty, Transplant surgery, business.industry, Internal medicine, General surgery, medicine, business, Angiology
Published: 2019
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9. Outcome of endovascular therapy in stroke with large vessel occlusion and mild symptoms

Author: Timo Kahles, Henrik Gensicke, Leo H. Bonati, Mandy D. Müller, Marcel Arnold, Georg Kägi, Stefania Nannoni, Giulio Disanto, Urs Fischer, Alessandro Cianfoni, Claudio Staedler, Krassen Nedeltchev, Carlo W. Cereda, Giovanni Bianco, Sebastian Thilemann, Emmanuel Carrera, Andreas R. Luft, Mirjam Rachel Heldner, Johannes Kaesmacher, Simon Jung, Patrik Michel, Concetta Manno, University of Zurich, and Cereda, Carlo W
Subjects: Male, medicine.medical_specialty, Stroke/epidemiology/surgery, 610 Medicine & health, Endovascular therapy, Severity of Illness Index, Brain Ischemia, Disability Evaluation, 03 medical and health sciences, 0302 clinical medicine, Modified Rankin Scale, Internal medicine, Severity of illness, Clinical endpoint, Humans, Medicine, cardiovascular diseases, Registries, 030212 general & internal medicine, Stroke, Aged, Retrospective Studies, Brain Ischemia/epidemiology/surgery, business.industry, Endovascular Procedures, Retrospective cohort study, Odds ratio, Middle Aged, medicine.disease, Confidence interval, 10040 Clinic for Neurology, ddc:616.8, 2728 Neurology (clinical), Mild symptoms, Treatment Outcome, cardiovascular system, Cardiology, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Large vessel occlusion
Abstract: ObjectiveTo compare outcomes after endovascular therapy (EVT) and IV thrombolysis (IVT) in patients with stroke with emergent large vessel occlusion (LVO) and mild neurologic deficits.MethodsThis was a retrospective analysis of patients from the Swiss Stroke Registry with admission NIH Stroke Scale score ≤5 and LVO treated by EVT (± IVT) vs IVT alone. The primary endpoint was favorable functional outcome (modified Rankin Scale [mRS] score 0–1) at 3 months. Secondary outcomes were independence (mRS score 0–2), mRS score (ordinal shift analysis), and survival with high disability (mRS score 4–5). Safety endpoints were mortality and symptomatic hemorrhage.ResultsOf 11,356 patients, 312 met the criteria and propensity score method matched 108 in each group. A comparably large proportion of patients with EVT and IVT had favorable outcome (63% vs 65.7% respectively; odds ratio 0.94, 95% confidence interval 0.51–1.72; p = 0.840). Patients with EVT showed a nonsignificant trend toward higher mRS score at 3 months (p = 0.717), while the proportion of surviving patients with high disability was comparably very low in both groups (p = 0.419). Mortality was slightly higher among those with EVT (9.3% vs 2.8%; p = 0.06), and symptomatic intracranial hemorrhage was a rare event in both groups (2.8% vs 0%; p = 0.997).ConclusionsIn acute ischemic stroke, EVT and IVT appear similarly effective in achieving favorable outcome at 3 months for patients with LVO and mild neurologic symptoms. EVT might be marginally inferior to IVT regarding outcome across all levels of disability and mortality. Further studies are required to determine whether certain subgroups of patients with LVO and mild symptoms benefit from EVT.Classification of evidenceThis study provides Class III evidence that patients with LVO and mild symptoms receiving either EVT or IVT had similar favorable functional outcomes at 3 months.
Published: 2019
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10. Aspirin versus anticoagulation in cervical artery dissection (TREAT-CAD):an open-label, randomised, non-inferiority trial

Author: Stefan T Engelter, Christopher Traenka, Henrik Gensicke, Sabine A Schaedelin, Andreas R Luft, Barbara Goeggel Simonetti, Urs Fischer, Patrik Michel, Gaia Sirimarco, Georg Kägi, Jochen Vehoff, Krassen Nedeltchev, Timo Kahles, Lars Kellert, Sverre Rosenbaum, Regina von Rennenberg, Roman Sztajzel, Stephen L Leib, Simon Jung, Jan Gralla, Nicole Bruni, David Seiffge, Katharina Feil, Alexandros A Polymeris, Levke Steiner, Janne Hamann, Leo H Bonati, Alex Brehm, Gian Marco De Marchis, Nils Peters, Christoph Stippich, Christian H Nolte, Hanne Christensen, Susanne Wegener, Marios-Nikos Psychogios, Marcel Arnold, Philippe Lyrer, Valerian Altersberger, Thomas Fabbro, Urs Fisch, Joachim Fladt, Lisa Hert, Philippe A Lyrer, Marina Maurer, Alexandros Polymeris, Sabine Schaedelin, Sebastian Thilemann, Benjamin Wagner, Mirjam Heldner, David J Seiffge, Hubertus Mueller, Lukas Sveikata, Pamela Correia, Ashraf Eskandari, Ivo Meyer, Stefania Nannoni, Suzette Remillard, Alexandros Zachariadis, Georg Kaegi, Anna Mueller, Hebun J Erdur, and Jan F Scheitz
Subjects: Adult, Male, medicine.medical_specialty, medicine.drug_class, Denmark, Population, Carotid Artery, Internal, Dissection, 030204 cardiovascular system & hematology, Phenprocoumon, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Germany, medicine, Clinical endpoint, Humans, education, Stroke, Vertebral Artery Dissection, education.field_of_study, Acenocoumarol, Aspirin, business.industry, Warfarin, Anticoagulants, Vitamin K antagonist, Middle Aged, medicine.disease, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Platelet Aggregation Inhibitors, Switzerland, medicine.drug
Abstract: Background: Cervical artery dissection is a major cause of stroke in young people (aged
Published: 2021
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11. Abstract P407: Etiology And Outcomes Of Non-traumatic Intracerebral Hemorrhage - Data From The Swiss Stroke Registry

Author: Emmanuel Carrera, Stefan T. Engelter, Susanne Renaud, Philippe Lyrer, Madlaine Mueller, Christophe Bonvin, Marcel Arnold, Achim Mueller, Stephan Salmen, Susanne Wegener, Javier Fandino, Werner J. Z’Graggen, Ludwig Schelosky, Leo H. Bonati, Nils Peters, David J. Seiffge, Christian Berger, Georg Kaegi, Carlo W. Cereda, Julien Niederhaeuser, Rolf Sturzenegger, Alexandros A Polymeris, Martina Goeldlin, Krassen Nedeltchev, Bernhard Siepen, Manuel Bolognese, Tomas Dobrocky, Biljana Rodic, Timo Kahles, Marie-Luise Mono, Bastian Volbers, David Bervini, Friedrich Medlin, Urs Fischer, and Davide Strambo
Subjects: Advanced and Specialized Nursing, Intracerebral hemorrhage, Stroke registry, Pediatrics, medicine.medical_specialty, business.industry, medicine.disease, nervous system diseases, Non traumatic, medicine, Etiology, cardiovascular diseases, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, Amyloid angiopathy
Abstract: Background: We determined the frequency of different etiologies of non-traumatic intracerebral hemorrhage (ICH) and their association with clinical characteristics and outcomes. Methods: We analyzed data from consecutive ICH patients enrolled in the prospective Swiss Stroke Registry (2014-2019). Etiology of ICH was determined according to prespecified, mutually exclusive categories. We assessed prevalence of ICH etiologies, their association with clinical characteristics, functional independence (modified Rankin Scale 0-2), mortality, recurrent ICH and ischemic stroke at 3 months. Results: We included 2584 patients (median age 72y, IQR 64-82, 46.6% female, median NIHSS 10; IQR 3-15). 2037 patients (80%) had hypertension and 553 (22.3%) were on anticoagulants. Distribution of etiologies was as follows: Hypertension (n=1216 patients; 47.1% of all / 56.3% of patients with hypertension), unknown etiology (n=542, 21.0%), antithrombotic therapy (n=225, 8.7% of all / 38% of patients on anticoagulants), cerebral amyloid angiopathy (CAA, n=211, 8.2%), macro-vascular (n=121, 4.7%), other determined etiologies (n=269, 10.4%). Patients with hypertensive ICH had significantly higher NIHSS (median 9; IQR 4-16) and blood pressure levels (median systolic 176; IQR 156-195) on admission. Patients with CAA had significantly lower NIHSS at baseline (median 5; IQR 2-12). Three month follow-up was available for 2109/2584 patients (81.6%). 820 (38.9%) were functionally independent, 658 have died (31.2%). Hypertensive ICH was associated with an increased rate of functional independence (aOR =1.42, 95%CI 1.06-1.90, p=0.02). 5.2% of patients had a cerebrovascular event within 3 months. CAA was associated with a high risk of recurrent ICH (HR 6.95, 95%CI 3.05-15.84, p Conclusions: In Swiss Stroke Units and Centers, one of two patients has ICH from a different cause than hypertension. The rate of functionally independent patients at 3 months seems higher than mortality. Absolute and relative risks of recurrent ICH and ischemic stroke after recent ICH differ among underlying etiologies.
Published: 2021
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12. The Tumor Profiler Study: integrated, multi-omic, functional tumor profiling for clinical decision support

Author: René Holtackers, Simone Muenst, Martin Zoche, Rudolf Aebersold, Stéphane Chevrier, Tobias Schär, Bettina Sobottka, Marc Zimmermann, Abdullah Kahraman, Lucas Pelkmans, Faisal Alquaddoomi, Philip Jermann, Natascha Santacroce, Andreas Wicki, Norbert Wey, Nora C. Toussaint, Monica-Andreea Drăgan, Mattheus H.E. Wildschut, Ruben Casanova, Shuqing Yu, Markus Tolnay, Marcus Vetter, Mustafa Anil Tuncel, Ximena Bonilla, Stefan Nicolet, Gabriele Gut, Stefan G. Stark, Philipp Markolin, Bruno S. Frey, Ramona Schlenker, Rebekka Wegmann, Walter P. Weber, Lara Bernasconi, Emanuela S. Milani, Viktor H. Koelzer, Christian Rommel, Christian P. Kunze, Sylvia Herter, Cinzia Esposito, Gabriela Senti, Michael Prummer, Katja Eschbach, Bernd Wollscheid, Riccardo Murri, Salvatore Piscuoglio, Mathilde Ritter, Mitchell P. Levesque, Christian Beisel, Tim M. Jaeger, Viola Heinzelmann-Schwarz, Gunnar Rätsch, Severin Schwan, Marina Bacac, Reinhard Dummer, Joanna Ficek, Sandra Goetze, Tatjana Vlajnic, Martin Erkens, Ilaria Alborelli, Ulrike Menzel, Vinko Tosevski, Markus G. Manz, Werner Kuebler, Detlef Günther, Julian M. Metzler, Daniel J. Stekhoven, Christian Kurzeder, Anja Frei, Tamara Huesser, Marta Nowak, Melike Ak, Francis Jacob, Gregor Zuend, Berend Snijder, Martina Haberecker, Pirmin Haeuptle, Anja Irmisch, Maya D'Costa, Linda Grob, Natalia Chicherova, Bernd Bodenmiller, Johanna Ziegler, Per-Olof Attinger, Jack Kuipers, Katharina Jahn, Nicola Miglino, Natalie R. Davidson, Jacobo Sarabia del Castillo, André Fedier, Fabian Wendt, Esther Danenberg, Pedro Ferreira, María Lourdes Rosano-Gonzalez, Sebastian Lugert, Andrea Jacobs, Charlotte K.Y. Ng, Alva Rani James, Tinu M. Thomas, André Kahles, Gerd Maass, Julien Mena, Jonas B. Albinus, Daniel Baumhoer, Sonali Andani, Petra C. Schwalie, Anne Bertolini, Marina Tusup, Franziska Singer, Alexandre Theocharides, Sandra Weber, Beatrice Beck-Schimmer, Sujana Sivapatham, Kjong-Van Lehmann, Stefanie Engler, Holger Moch, Niko Beerenwinkel, Vipin T. Sreedharan, Michael Weller, Audrey Van Drogen, Patrick G. A. Pedrioli, University of Zurich, Rätsch, Gunnar, and Levesque, Mitchell Paul
Subjects: 0301 basic medicine, Decision support system, Cancer Research, Computer science, Observational Trial, Clinical Decision-Making, 610 Medicine & health, Computational biology, Clinical decision support system, 1307 Cell Biology, 03 medical and health sciences, 0302 clinical medicine, Neoplasms, 10049 Institute of Pathology and Molecular Pathology, Humans, Profiling (information science), 1306 Cancer Research, Prospective Studies, Precision Medicine, business.industry, Computational Biology, 10177 Dermatology Clinic, 10060 Epidemiology, Biostatistics and Prevention Institute (EBPI), Cell Biology, Decision Support Systems, Clinical, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, 10032 Clinic for Oncology and Hematology, 2730 Oncology, Personalized medicine, business, 11493 Department of Quantitative Biomedicine
Abstract: The application and integration of molecular profiling technologies create novel opportunities for personalized medicine. Here, we introduce the Tumor Profiler Study, an observational trial combining a prospective diagnostic approach to assess the relevance of in-depth tumor profiling to support clinical decision-making with an exploratory approach to improve the biological understanding of the disease.
Published: 2021
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13. Prior Anticoagulation in Patients with Ischemic Stroke and Atrial Fibrillation

Author: Davide Strambo, Giovanni Bianco, Timo Kahles, Ludwig Schelosky, Mira Katan, Elisabeth Dirren, Christian Berger, David J. Seiffge, Roland Backhaus, Marcel Arnold, Mattia Branca, Patrik Michel, Julien Niederhäuser, Carlo W. Cereda, Stefan T. Engelter, Marie-Luise Mono, Emmanuel Carrera, Georg Kägi, Susanne Renaud, Urs Fischer, Christophe Bonvin, Biljana Rodic, Johannes Kaesmacher, Sylvan Albert, Krassen Nedeltchev, Gian Marco De Marchis, Pasquale Mordasini, Friedrich Medlin, Mirjam Rachel Heldner, Leo H. Bonati, Simon Jung, Stephan Salmen, Manuel Bolognese, Michael Schaerer, Alexander A. Tarnutzer, Jan Gralla, Thomas Raphael Meinel, Jochen Vehoff, Investigators of the Swiss Stroke Registry, Lyrer, P., Peters, N., Polymeris, A., Thilemann, S., Altersberger, V., Blackham, K., Dittrich, T., El Mekabaty, A., Fladt, J., Fisch, U., Gensicke, H., Hert, L., Manuzzi, S., Psychogios, M., Maurer, M., Traenka, C., Tsogkas, I., Wagner, B., Zietz, A., Brehm, A., Meya, L., Sarikaya, H., Goeldlin, M., Vynckier, J., Mamaari, B., Siepen, B., Mueller, M., Eskandari, A., Pantazou, V., Wegener, S., Mueller, A., Schütz, V., Pokorny, T., Luft, A., Albert, S., Sturzenegger, R., Humm, A., Cuendet, D., Accolla, E., Annoni, J.M., Foucras, S., Minkner, K.K., Olivier, P., Kelemen, P., Brodo, G., Cordier, M., Jurgutiene, V., Sotomayor, G.T., and Fisch, L.
Subjects: 0301 basic medicine, medicine.medical_specialty, medicine.medical_treatment, 610 Medicine & health, macromolecular substances, Anticoagulants, Anticoagulation, DOAC, Ischaemic Stroke, Thrombectomy, Thrombolysis, Brain Ischemia, 03 medical and health sciences, 0302 clinical medicine, Modified Rankin Scale, Interquartile range, Internal medicine, Atrial Fibrillation, medicine, cardiovascular diseases, Research Articles, Ischemic Stroke, business.industry, Confounding, Atrial fibrillation, Odds ratio, medicine.disease, Confidence interval, ddc:616.8, 030104 developmental biology, Neurology, Cardiology, Neurology (clinical), business, 030217 neurology & neurosurgery, Research Article, Cohort study
Abstract: OBJECTIVE The aim was to evaluate, in patients with atrial fibrillation (AF) and acute ischemic stroke, the association of prior anticoagulation with vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) with stroke severity, utilization of intravenous thrombolysis (IVT), safety of IVT, and 3-month outcomes. METHODS This was a cohort study of consecutive patients (2014-2019) on anticoagulation versus those without (controls) with regard to stroke severity, rates of IVT/mechanical thrombectomy, symptomatic intracranial hemorrhage (sICH), and favorable outcome (modified Rankin Scale score 0-2) at 3 months. RESULTS Of 8,179 patients (mean [SD] age, 79.8 [9.6] years; 49% women), 1,486 (18%) were on VKA treatment, 1,634 (20%) on DOAC treatment at stroke onset, and 5,059 controls. Stroke severity was lower in patients on DOACs (median National Institutes of Health Stroke Scale 4, [interquartile range 2-11]) compared with VKA (6, [2-14]) and controls (7, [3-15], p
Published: 2021
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14. Association of Glucose‐Dependent Insulinotropic Polypeptide Levels With Cardiovascular Mortality in Patients With Acute Myocardial Infarction

Author: R W Mertens, Julia Moellmann, Moritz Biener, M C Arrivas, Hugo A. Katus, Marcia Viviane Rückbeil, Evangelos Giannitsis, Florian Kahles, Michael Lehrke, and Nikolaus Marx
Subjects: Male, medicine.medical_specialty, Myocardial Infarction, Gastric Inhibitory Polypeptide, Receptors, Gastrointestinal Hormone, Germany, Internal medicine, Research Letter, medicine, Humans, In patient, Myocardial infarction, Aged, Proportional Hazards Models, Cardiovascular mortality, business.industry, Middle Aged, medicine.disease, Acute Disease, Multivariate Analysis, Cardiology, Glucose-dependent insulinotropic polypeptide, Female, Cardiology and Cardiovascular Medicine, business, Acute Coronary Syndromes, Biomarkers
Abstract: Journal of the American Heart Association : JAHA 10(13), e019477 (2021). doi:10.1161/JAHA.120.019477, Published by Association, New York, NY
Published: 2021
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15. Establishing standardized immune phenotyping of metastatic melanoma by digital pathology

Author: Bettina Sobottka, Marta Nowak, Anja Laura Frei, Martina Haberecker, Samuel Merki, Mitchell P. Levesque, Reinhard Dummer, Holger Moch, Viktor Hendrik Koelzer, Rudolf Aebersold, Melike Ak, Faisal S. Al-Quaddoomi, Jonas Albinus, Ilaria Alborelli, Sonali Andani, Per-Olof Attinger, Marina Bacac, Daniel Baumhoer, Beatrice Beck-Schimmer, Niko Beerenwinkel, Christian Beisel, Lara Bernasconi, Anne Bertolini, Bernd Bodenmiller, Ximena Bonilla, Ruben Casanova, Stéphane Chevrier, Natalia Chicherova, Maya D'Costa, Esther Danenberg, Natalie Davidson, Monica-Andreea Drăganmoch, Stefanie Engler, Martin Erkens, Katja Eschbach, Cinzia Esposito, André Fedier, Pedro Ferreira, Joanna Ficek, Bruno Frey, Sandra Goetze, Linda Grob, Gabriele Gut, Detlef Günther, Pirmin Haeuptle, Viola Heinzelmann-Schwarz, Sylvia Herter, Rene Holtackers, Tamara Huesser, Anja Irmisch, Francis Jacob, Andrea Jacobs, Tim M. Jaeger, Katharina Jahn, Alva R. James, Philip M. Jermann, André Kahles, Abdullah Kahraman, Werner Kuebler, Jack Kuipers, Christian P. Kunze, Christian Kurzeder, Kjong-Van Lehmann, Sebastian Lugert, Gerd Maass, Markus G. Manz, Philipp Markolin, Julien Mena, Ulrike Menzel, Julian M. Metzler, Nicola Miglino, Emanuela S. Milani, Simone Muenst, Riccardo Murri, Charlotte K.Y. Ng, Stefan Nicolet, Patrick G.A. Pedrioli, Lucas Pelkmans, Salvatore Piscuoglio, Michael Prummer, Mathilde Ritter, Christian Rommel, María L. Rosano-González, Gunnar Rätsch, Natascha Santacroce, Jacobo Sarabia del Castillo, Ramona Schlenker, Petra C. Schwalie, Severin Schwan, Tobias Schär, Gabriela Senti, Franziska Singer, Sujana Sivapatham, Berend Snijder, Vipin T. Sreedharan, Stefan Stark, Daniel J. Stekhoven, Alexandre P.A. Theocharides, Tinu M. Thomas, Markus Tolnay, Vinko Tosevski, Nora C. Toussaint, Mustafa A. Tuncel, Marina Tusup, Audrey Van Drogen, Marcus Vetter, Tatjana Vlajnic, Sandra Weber, Walter P. Weber, Rebekka Wegmann, Michael Weller, Fabian Wendt, Norbert Wey, Andreas Wicki, Mattheus HE Wildschut, Bernd Wollscheid, Shuqing Yu, Johanna Ziegler, Marc Zimmermann, Martin Zoche, Gregor Zuend, University of Zurich, Sobottka-Brillout, Bettina, and Koelzer, Viktor Hendrik
Subjects: Pathology, medicine.medical_specialty, Stromal cell, 610 Medicine & health, Disease, Predictive markers, Article, Pathology and Forensic Medicine, 1307 Cell Biology, Immune system, 10049 Institute of Pathology and Molecular Pathology, 1312 Molecular Biology, Medicine, Compartment (pharmacokinetics), Molecular Biology, Melanoma, business.industry, 10177 Dermatology Clinic, Digital pathology, 10060 Epidemiology, Biostatistics and Prevention Institute (EBPI), Cell Biology, Biomarker (cell), 2734 Pathology and Forensic Medicine, 10032 Clinic for Oncology and Hematology, Cohort, Imaging the immune system, business, CD8
Abstract: CD8+ tumor-infiltrating T cells can be regarded as one of the most relevant predictive biomarkers in immune-oncology. Highly infiltrated tumors, referred to as inflamed (clinically “hot”), show the most favorable response to immune checkpoint inhibitors in contrast to tumors with a scarce immune infiltrate called immune desert or excluded (clinically “cold”). Nevertheless, quantitative and reproducible methods examining their prevalence within tumors are lacking. We therefore established a computational diagnostic algorithm to quantitatively measure spatial densities of tumor-infiltrating CD8+ T cells by digital pathology within the three known tumor compartments as recommended by the International Immuno-Oncology Biomarker Working Group in 116 prospective metastatic melanomas of the Swiss Tumor Profiler cohort. Workflow robustness was confirmed in 33 samples of an independent retrospective validation cohort. The introduction of the intratumoral tumor center compartment proved to be most relevant for establishing an immune diagnosis in metastatic disease, independent of metastatic site. Cut-off values for reproducible classification were defined and successfully assigned densities into the respective immune diagnostic category in the validation cohort with high sensitivity, specificity, and precision. We provide a robust diagnostic algorithm based on intratumoral and stromal CD8+ T-cell densities in the tumor center compartment that translates spatial densities of tumor-infiltrating CD8+ T cells into the clinically relevant immune diagnostic categories “inflamed”, “excluded”, and “desert”. The consideration of the intratumoral tumor center compartment allows immune phenotyping in the clinically highly relevant setting of metastatic lesions, even if the invasive margin compartment is not captured in biopsy material., The authors present a robust diagnostic algorithm based on digital pathology and image analysis that quantifies intratumoral and stromal CD8+ T-cell densities in the tumor center and invasive margin compartment in metastatic melanoma. Spatial CD8+ T-cell densities are translated into the clinically relevant immune diagnostic categories “inflamed”, “excluded”, and “desert”. Their approach also allows efficient immune phenotyping of metastatic lesions, on biopsy material or even in the absence of material from the invasive margin.
Published: 2021
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16. SCIM: universal single-cell matching with unpaired feature sets

Author: Stark, Stefan G, Ficek, Joanna, Locatello, Francesco, Bonilla, Ximena, Chevrier, Stéphane, Singer, Franziska, Aebersold, Rudolf, Al-Quaddoomi, Faisal S, Albinus, Jonas, Alborelli, Ilaria, Andani, Sonali, Attinger, Per-Olof, Bacac, Marina, Baumhoer, Daniel, Beck-Schimmer, Beatrice, Beerenwinkel, Niko, Beisel, Christian, Bernasconi, Lara, Bertolini, Anne, Bodenmiller, Bernd, Casanova, Ruben, Chicherova, Natalia, D'Costa, Maya, Danenberg, Esther, Davidson, Natalie, gan, Monica-Andreea Dră, Dummer, Reinhard, Engler, Stefanie, Erkens, Martin, Eschbach, Katja, Esposito, Cinzia, Fedier, André, Ferreira, Pedro, Frei, Anja L, Frey, Bruno, Goetze, Sandra, Grob, Linda, Gut, Gabriele, Günther, Detlef, Haberecker, Martina, Haeuptle, Pirmin, Heinzelmann-Schwarz, Viola, Herter, Sylvia, Holtackers, Rene, Huesser, Tamara, Irmisch, Anja, Jacob, Francis, Jacobs, Andrea, Jaeger, Tim M, Jahn, Katharina, James, Alva R, Jermann, Philip M, Kahles, André, Kahraman, Abdullah, Koelzer, Viktor H, Kuebler, Werner, Kuipers, Jack, Kunze, Christian P, Kurzeder, Christian, Lehmann, Kjong-Van, Levesque, Mitchell, Lugert, Sebastian, Maass, Gerd, Manz, Markus, Markolin, Philipp, Mena, Julien, Menzel, Ulrike, Metzler, Julian M, Miglino, Nicola, Milani, Emanuela S, Moch, Holger, Muenst, Simone, Murri, Riccardo, Ng, Charlotte KY, Nicolet, Stefan, Nowak, Marta, Pedrioli, Patrick GA, Pelkmans, Lucas, Piscuoglio, Salvatore, Prummer, Michael, Ritter, Mathilde, Rommel, Christian, Rosano-González, María L, Rätsch, Gunnar, Santacroce, Natascha, Castillo, Jacobo Sarabia del, Schlenker, Ramona, Schwalie, Petra C, Schwan, Severin, Schär, Tobias, Senti, Gabriela, Sivapatham, Sujana, Snijder, Berend, Sobottka, Bettina, Sreedharan, Vipin T, Stark, Stefan, Stekhoven, Daniel J, Theocharides, Alexandre PA, Thomas, Tinu M, Tolnay, Markus, Tosevski, Vinko, Toussaint, Nora C, Tuncel, Mustafa A, Tusup, Marina, Drogen, Audrey Van, Vetter, Marcus, Vlajnic, Tatjana, Weber, Sandra, Weber, Walter P, Wegmann, Rebekka, Weller, Michael, Wendt, Fabian, Wey, Norbert, Wicki, Andreas, Wollscheid, Bernd, Yu, Shuqing, Ziegler, Johanna, Zimmermann, Marc, Zoche, Martin, Zuend, Gregor, and University of Zurich
Subjects: Statistics and Probability, 1303 Biochemistry, AcademicSubjects/SCI01060, Computer science, 610 Medicine & health, computer.software_genre, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Text mining, 1312 Molecular Biology, 1706 Computer Science Applications, Humans, Profiling (information science), 2613 Statistics and Probability, Molecular Biology, 030304 developmental biology, Data, 0303 health sciences, Sequence Analysis, RNA, business.industry, Gene Expression Profiling, Autoencoder, Computer Science Applications, Computational Mathematics, Computational Theory and Mathematics, 10032 Clinic for Oncology and Hematology, Bipartite graph, Data mining, Single-Cell Analysis, business, computer, 2605 Computational Mathematics, Algorithms, Software, 030217 neurology & neurosurgery, Data integration, 1703 Computational Theory and Mathematics
Abstract: Motivation: Recent technological advances have led to an increase in the production and availability of single-cell data. The ability to integrate a set of multi-technology measurements would allow the identification of biologically or clinically meaningful observations through the unification of the perspectives afforded by each technology. In most cases, however, profiling technologies consume the used cells and thus pairwise correspondences between datasets are lost. Due to the sheer size single-cell datasets can acquire, scalable algorithms that are able to universally match single-cell measurements carried out in one cell to its corresponding sibling in another technology are needed. Results: We propose Single-Cell data Integration via Matching (SCIM), a scalable approach to recover such correspondences in two or more technologies. SCIM assumes that cells share a common (low-dimensional) underlying structure and that the underlying cell distribution is approximately constant across technologies. It constructs a technology-invariant latent space using an autoencoder framework with an adversarial objective. Multi-modal datasets are integrated by pairing cells across technologies using a bipartite matching scheme that operates on the low-dimensional latent representations. We evaluate SCIM on a simulated cellular branching process and show that the cell-to-cell matches derived by SCIM reflect the same pseudotime on the simulated dataset. Moreover, we apply our method to two real-world scenarios, a melanoma tumor sample and a human bone marrow sample, where we pair cells from a scRNA dataset to their sibling cells in a CyTOF dataset achieving 90% and 78% cell-matching accuracy for each one of the samples, respectively., Bioinformatics, 36 (S2), ISSN:1367-4803, ISSN:1460-2059
Published: 2020
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17. Peptide YY (PYY) Is Associated with Cardiovascular Risk in Patients with Acute Myocardial Infarction

Author: Evangelos Giannitsis, Marcia Viviane Rückbeil, Mohammad Almalla, Moritz Biener, Nikolaus Marx, J. Schroeder, Julia Moellmann, Florian Kahles, Michael Lehrke, Elias Haj-Yehia, Matthias Rau, R W Mertens, and Hugo A. Katus
Subjects: cardiovascular risk, medicine.medical_specialty, Renal function, lcsh:Medicine, 030209 endocrinology & metabolism, Disease, 030204 cardiovascular system & hematology, Article, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, Internal medicine, Medicine, Myocardial infarction, cardiovascular diseases, PYY, business.industry, Proportional hazards model, Confounding, digestive, oral, and skin physiology, lcsh:R, General Medicine, medicine.disease, mortality, myocardial infarction, Peptide YY, Heart failure, Cardiology, business, hormones, hormone substitutes, and hormone antagonists, gut hormone
Abstract: Aims: Recent studies have found circulating concentrations of the gastrointestinal hormone GLP-1 to be an excellent predictor of cardiovascular risk in patients with myocardial infarction. This illustrates a yet not appreciated crosstalk between the gastrointestinal and cardiovascular systems, which requires further investigation. The gut-derived hormone Peptide YY (PYY) is secreted from the same intestinal L-cells as GLP-1. Relevance of PYY in the context of cardiovascular disease has not been explored. In this study, we aimed to investigate PYY serum concentrations in patients with acute myocardial infarction and to evaluate their association with cardiovascular events. Material and Methods: PYY levels were assessed in 834 patients presenting with acute myocardial infarction (553 Non-ST-Elevation Myocardial Infarction (NSTEMI) and 281 ST-Elevation Myocardial Infarction (STEMI)) at the time of hospital admission. The composite outcomes of first occurrence of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke (3-P-MACE), and all-cause mortality were assessed with a median follow-up of 338 days. Results: PYY levels were significantly associated with age and cardiovascular risk factors, including hypertension, diabetes, and kidney function in addition to biomarkers of heart failure (NT-pro BNP) and inflammation (hs-CRP). Further, PYY was significantly associated with 3-P-MACE (HR: 1.7, 95% CI: 1&ndash, 2.97, p = 0.0495) and all-cause mortality (HR: 2.69, 95% CI: 1.61&ndash, 4.47, p = 0.0001) by univariable Cox regression analyses, which was however lost after adjusting for multiple confounders. Conclusions: PYY levels are associated with parameters of cardiovascular risk as well as cardiovascular events and mortality in patients presenting with acute myocardial infarction. However, this significant association is lost after adjustment for further confounders.
Published: 2020

18. Sleep-Disordered Breathing and Nocturnal Hypoxemia in Precapillary Pulmonary Hypertension: Prevalence, Pathophysiological Determinants, and Clinical Consequences

Author: Simon Herkenrath, Claudio Passino, Michele Emdin, Matthias Boentert, Michael Mohr, Florian Kahles, Michael Dreher, Matthew T. Naughton, Jens Spiesshoefer, Katharina Harre, Winfried Randerath, Anca Florian, Ali Yilmaz, Binaya Regmi, and Alberto Giannoni
Subjects: Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, medicine.drug_class, Hypoxemia, Pulmonary hypertension, Right heart failure, Sleep-disordered breathing, Hypertension, Pulmonary, Polysomnography, Physical examination, 03 medical and health sciences, 0302 clinical medicine, Sleep Apnea Syndromes, Internal medicine, medicine, Natriuretic peptide, Prevalence, Humans, Clinical significance, 030212 general & internal medicine, Hypoxia, Aged, Sleep Apnea, Obstructive, medicine.diagnostic_test, business.industry, Cardiorespiratory fitness, Middle Aged, medicine.disease, respiratory tract diseases, Obstructive sleep apnea, 030228 respiratory system, Breathing, Cardiology, Female, medicine.symptom, business
Abstract: Background and objective: The clinical relevance and interrelation of sleep-disordered breathing and nocturnal hypoxemia in patients with precapillary pulmonary hypertension (PH) is not fully understood. Methods: Seventy-one patients with PH (age 63 ± 15 years, 41% male) and 35 matched controls were enrolled. Patients with PH underwent clinical examination with assessment of sleep quality, daytime sleepiness, 6-minute walk distance (6MWD), overnight cardiorespiratory polygraphy, lung function, hypercapnic ventilatory response (HCVR; by rebreathing technique), amino-terminal pro-brain natriuretic peptide (NT-proBNP) levels, and cardiac MRI (n = 34). Results: Prevalence of obstructive sleep apnea (OSA) was 68% in patients with PH (34% mild, apnea-hypopnea index [AHI] ≥5 to p < 0.01). Only 1 patient with PH showed predominant central sleep apnea (CSA). Nocturnal hypoxemia (mean oxygen saturation [SpO2] 2, self-reported sleep quality, 6MWD, HCVR, and lung and cardiac function between patients with moderate to severe OSA and those with mild or no OSA (all p > 0.05). Right ventricular (RV) end-diastolic (r = −0.39; p = 0.03) and end-systolic (r = −0.36; p = 0.04) volumes were inversely correlated with mean nocturnal SpO2 but not with measures of OSA severity or daytime clinical variables. Conclusion: OSA, but not CSA, is highly prevalent in patients with PH, and OSA severity is not associated with nighttime SpO2, clinical and functional status. Nocturnal hypoxemia is a frequent finding and (in contrast to OSA) relates to structural RV remodeling in PH.
Published: 2020

19. Carotid-cavernous sinus fistula following mechanical thrombectomy in acute ischaemic stroke: a rare complication

Author: Hanspeter E. Killer, Philipp Gruber, Lukas Andereggen, Jatta Berberat, Javier Anon, Basil E Grüter, and Timo Kahles
Subjects: medicine.medical_specialty, 030218 nuclear medicine & medical imaging, Brain Ischemia, 03 medical and health sciences, 0302 clinical medicine, Carotid-Cavernous Sinus Fistula, medicine.artery, medicine, Humans, Radiology, Nuclear Medicine and imaging, Carotid-cavernous fistula, Sinus (anatomy), Neuroradiology, Ischemic Stroke, Thrombectomy, business.industry, Middle Aged, medicine.disease, Embolization, Therapeutic, Surgery, Cerebral Angiography, Stroke, medicine.anatomical_structure, Middle cerebral artery, Cavernous sinus, cardiovascular system, Neurology (clinical), Neurosurgery, Internal carotid artery, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery
Abstract: Carotid-cavernous sinus fistulas (CCFs) are abnormal communications between the internal carotid artery (ICA) and the cavernous sinus (CS). Direct CCFs are associated with trauma or are iatrogenic complications of neuroendovascular procedures. Meanwhile, mechanical endovascular thrombectomy (MT) in acute ischaemic stroke (AIS) patients with large vessel occlusion (LVO) has been established as a common treatment approach. However, MT is not without its risks of complications, and only a few reports exist on CCF occurring after MT. Here, we present a case of a 63-year-old patient with iatrogenic high-flow CCF of the right horizontal cavernous ICA segment (C4) following repeated MT due to LVO of the middle cerebral artery, and the recent literature is reviewed.
Published: 2020

20. GLP-1 is an independent predictor of long-term mortality in patients with myocardial infarction complicated by cardiogenic shock – a substudy of the IABP-SHOCK II trial

Author: N Thelemann, Florian Kahles, Michael Lehrke, Holger Thiele, Christian Jung, Steffen Desch, Uwe Zeymer, Karl Werdan, Corinna Lebherz, Volker Adams, G Fuernau, Nikolaus Marx, and Ingo Eitel
Subjects: medicine.medical_specialty, business.industry, Cardiogenic shock, medicine.disease, Independent predictor, Intensive care unit, law.invention, law, Shock (circulatory), Internal medicine, Diabetes mellitus, medicine, Cardiology, In patient, Long term mortality, Myocardial infarction, medicine.symptom, Cardiology and Cardiovascular Medicine, business
Abstract: Background The incretin hormone Glucagon-like-peptide 1 (GLP-1) is a major stimulus for glucose dependent insulin secretion and holds cardioprotective efficacy. This has made the GLP-1 system a preferred target for diabetes therapy. Secretion of GLP-1 happens in response to nutritional but also inflammatory stimuli. Consequently, marked elevation of circulating GLP-1 levels were found in critically ill patients featuring marked association to markers of inflammation. Purpose Our study sought to investigate GLP-1 levels in patients with cardiogenic shock (CS) complicating myocardial infarction and a possible prognostic correlation to short- and long-term outcome. Methods We serially assessed circulating GLP-1 levels in a prospectively planned biomarker substudy in the IABP-SHOCK II trial. Blood samples were drawn during index PCI and at day 2. The blood was centrifuged immediately, and serum was frozen at −87°C. GLP-1 was measured with a standard ELISA-kit. All-cause mortality at short- (30 days), intermediate- (1 year) and long-term (6 years) follow-up was used for outcome assessment. Results In this study we found circulating GLP-1 to be markedly elevated in patients with myocardial infarction complicated by CS (n=172) at time of index PCI. Patients with fatal short-term outcome (n=70) exhibited higher GLP-1 levels (86 [45–130] pM) at ICU admission in comparison to patients with 30-day survival (48 [33–78] pM; pmedian were predictive of short- (hazard ratio [HR] 2.43; 95% confidence interval [CI] 1.50–3.94; pmedian from day 30 to 1 year (HR 2.56; 95% CI 1.08–6.09; p=0.03). In contrast, beyond 1 year up to 6 years no difference has been observed anymore (HR 1.02; 95% CI 0.41–2.58; p=0.96). Conclusions Elevated plasma levels of GLP-1 are an independent predictor for impaired prognosis in patients with myocardial infarction complicated by CS at short-, intermediate and long-term follow-up. In a landmark analysis this prognostic effect is sustained up to 1 year. The functional relevance of GLP-1 in this context is currently unknown and needs further investigations. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): German Research Foundation (DFG), German Heart Research Foundation
Published: 2020
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21. The gut hormone GLP-2 predicts cardiovascular risk in patients with acute myocardial infarction

Author: Moritz Biener, Julia Moellmann, R W Mertens, M C Arrivas, M V Rueckbeil, Evangelos Giannitsis, Hugo A. Katus, Florian Kahles, Michael Lehrke, Corinna Lebherz, and Nikolaus Marx
Subjects: medicine.medical_specialty, business.industry, Internal medicine, medicine, Cardiology, In patient, Myocardial infarction, Cardiology and Cardiovascular Medicine, medicine.disease, business, hormones, hormone substitutes, and hormone antagonists, Hormone
Abstract: Background GLP-1 and GLP-2 (glucagon-like peptide-1/2) are gut derived hormones that are co-secreted from intestinal L-cells in response to food intake. While GLP-1 is known to induce postprandial insulin secretion, GLP-2 enhances intestinal nutrient absorption and is clinically used for the treatment of patients with short bowel syndrome. The relevance of the GLP-2 system for cardiovascular disease is unknown. Purpose The aim of this study was to assess the predictive capacity of GLP-2 for cardiovascular prognosis in patients with myocardial infarction. Methods Total GLP-2 levels, NT-proBNP concentrations and the Global Registry of Acute Coronary Events (GRACE) score were assessed at time of admission in 918 patients with myocardial infarction, among them 597 patients with NSTEMI and 321 with STEMI. The primary composite outcome of the study was the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (3-P-MACE) with a median follow-up of 311 days. Results Kaplan-Meier survival plots (separated by the median of GLP-2 with a cut-off value of 4.4 ng/mL) and univariable cox regression analyses found GLP-2 values to be associated with adverse outcome (logarithmized GLP-2 values HR: 2.87; 95% CI: 1.75–4.68; p Conclusions In patients admitted with acute myocardial infarction, GLP-2 levels are associated with adverse cardiovascular prognosis. This demonstrates a strong yet not appreciated crosstalk between the heart and the gut with relevance for cardiovascular outcome. Future studies are needed to further explore this crosstalk with the possibility of new treatment avenues for cardiovascular disease. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): German Society of Cardiology (DGK), German Research Foundation (DFG)
Published: 2020
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22. Adipocyte calcium sensing receptor is not involved in visceral adipose tissue inflammation or atherosclerosis development in hyperlipidemic Apoe

Author: Yvonne Jansen, Christian Weber, Sai Sahana Sundararaman, Florian Kahles, Michael Lehrke, Selin Gencer, Andrea Bonnin Marquez, Emiel P. C. van der Vorst, Linsey J. F. Peters, Yi Yan, Sumra Nazir, Yvonne Döring, Joachim Jankowski, Erik A.L. Biessen, Pathologie, RS: Carim - B07 The vulnerable plaque: makers and markers, Biochemie, and RS: Carim - B01 Blood proteins & engineering
Subjects: 0301 basic medicine, Mice, Knockout, ApoE, Adipose tissue, 030204 cardiovascular system & hematology, Systemic inflammation, DISEASE, ACTIVATION, chemistry.chemical_compound, Mice, 0302 clinical medicine, Adipocyte, Adipocytes, 610 Medicine & health, Receptor, TUMOR-NECROSIS-FACTOR, Multidisciplinary, PROLIFERATION, Plaque, Atherosclerotic, Mechanisms of disease, OBESITY, Medicine, Tumor necrosis factor alpha, medicine.symptom, Calcium-sensing receptor, EXTRACELLULAR CA2+-SENSING RECEPTOR, EXPRESSION, medicine.medical_specialty, Science, PARATHYROID-HORMONE, Inflammation, Hyperlipidemias, KAPPA-B, Intra-Abdominal Fat, Article, 03 medical and health sciences, Internal medicine, medicine, INTERLEUKIN-6 PRODUCTION, Animals, Humans, business.industry, Cardiovascular biology, Disease Models, Animal, 030104 developmental biology, Endocrinology, chemistry, business, Receptors, Calcium-Sensing, Homeostasis
Abstract: Scientific reports 11, 10409 (2021). doi:10.1038/s41598-021-89893-y, Published by Macmillan Publishers Limited, part of Springer Nature, [London]
Published: 2020
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23. Automating GUI Testing with Image-Based Deep Reinforcement Learning

Author: Julen Kahles, Juha Eskonen, and Joel Reijonen
Subjects: 0209 industrial biotechnology, Computer science, business.industry, 020208 electrical & electronic engineering, Usability, Manual testing, 02 engineering and technology, Graphical user interface testing, Automation, 020901 industrial engineering & automation, Test case, Asynchronous communication, Human–computer interaction, 0202 electrical engineering, electronic engineering, information engineering, Reinforcement learning, business, Graphical user interface
Abstract: Users interact with modern applications and devices through graphical user interfaces (GUIs). To ensure intuitive and easy usability, the GUIs need to be tested, where developers aim at finding possible bugs and inconsistent functionality. Manual GUI testing requires time and effort, and thus, its efficiency can be improved with automation. Conventional automation tools for GUI testing reduce the burden of manual testing but also introduce challenges in the maintenance of test cases. In order to overcome these issues, we propose a deep-reinforcement-learning-based (DRL) solution for automated and adaptive GUI testing. Specifically, we propose and evaluate the performance of an image-based DRL solution. We adapt the asynchronous advantage actor-critic (A3C) algorithm to GUI testing inspired by how a human uses a GUI. We feed screenshots of the GUI as the input and let the algorithm decide how to interact with GUI components. We observe that our solution can achieve up to six times higher exploration efficiency compared to selected baseline algorithms. Moreover, our solution is more efficient than inexperienced human users and almost as efficient as an experienced human user in our experimental GUI testing scenario. For these reasons, image-based DRL exploration can be considered as a viable GUI testing method.
Published: 2020
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24. Lipoprotein(a) is associated with large artery atherosclerosis stroke aetiology and stroke recurrence among patients below the age of 60 years: results from the BIOSIGNAL study

Author: George Ntaios, Alejandro Bustamante, Corinne Inauen, Georg Kägi, Gian Marco De Marchis, Leo H. Bonati, Arnold von Eckardstein, Marcel Arnold, Katharina Spanaus, Juliane Schweizer, Carlo W. Cereda, Thomas Pokorny, Timo Kahles, Alexander Benedikt Leichtle, Valerie Schütz, Markus F. F. Arnold, Christian Foerch, Laura P. Westphal, Mira Katan, Andreas R. Luft, Mandy D. Müller, Krassen Nedeltchev, Joan Montaner, Christos T. Nakas, Urs Fischer, Antonela Bicvic, University of Zurich, Arnold, Markus, and Arnold, Marcel
Subjects: medicine.medical_specialty, 610 Medicine & health, 030204 cardiovascular system & hematology, 2705 Cardiology and Cardiovascular Medicine, Brain Ischemia, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Recurrence, Risk Factors, Internal medicine, 540 Chemistry, Medicine, Humans, Prospective Studies, Risk factor, Stroke, 10038 Institute of Clinical Chemistry, biology, business.industry, Hazard ratio, Atrial fibrillation, Lipoprotein(a), Odds ratio, Arteries, Middle Aged, medicine.disease, Atherosclerosis, 10040 Clinic for Neurology, Cohort, biology.protein, Cardiology, 10023 Institute of Intensive Care Medicine, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery, Cohort study
Abstract: Aims Lipoprotein(a) [Lp(a)] is a recognized causal risk factor for atherosclerotic cardiovascular disease but its role for acute ischaemic stroke (AIS) is controversial. In this study, we evaluated the association of Lp(a) with large artery atherosclerosis (LAA) stroke and risk of recurrent cerebrovascular events in AIS patients. Methods and results For this analysis of the prospective, observational, multicentre BIOSIGNAL cohort study we measured Lp(a) levels in plasma samples of 1733 primarily Caucasian (98.6%) AIS patients, collected within 24 h after symptom onset. Primary outcomes were LAA stroke aetiology and recurrent cerebrovascular events (ischaemic stroke or transient ischaemic attack) within 1 year. We showed that Lp(a) levels are independently associated with LAA stroke aetiology [adjusted odds ratio 1.48, 95% confidence interval (CI) 1.14-1.90, per unit log10Lp(a) increase] and identified age as a potent effect modifier (Pinteraction =0.031) of this association. The adjusted odds ratio for LAA stroke in patients aged Conclusion Elevated Lp(a) was independently associated with LAA stroke aetiology and risk of recurrent cerebrovascular events among primarily Caucasian individuals aged
Published: 2020

25. Publisher Correction: Building an international consortium for tracking coronavirus health status

Author: Natalie R. Davidson, Jay Rajagopal, Gisel Booman, Andrew T. Chan, Ljupco Kocarev, Joshua Gale, Georgina Evans, Xihong Lin, Benjamin Geiger, Matej Orešič, Hagai Rossman, Ophir Shalem, Yonatan H. Grad, André Kahles, Tim D. Spector, Svetlana Ovchinnikova, Andrea Sboner, Phil Ewels, Ron Steinherz, Simon Anders, Faisal Alquaddoomi, Olli Kallioniemi, Eran Segal, Aline Muller, Iman Hajirasouliha, Alexandros Sigaras, Amir Gavrieli, Feng Zhang, Long H. Nguyen, Jana Prodanova, Silvano Coletti, Johan Rung, Smadar Shilo, Roman Jerala, Hedi Peterson, Gunnar Rätsch, Tomer Meir, Tal Bauman, Gregory Landua, Gary King, Han Altae-Tran, Ayya Keshet, David A. Drew, Casey S. Greene, Jaak Vilo, Olivier Elemento, William E. Allen, Ximena Bonilla, Ori Cohen, Ran D. Balicer, Yuval Dor, Irene Stevens, and Paul Wilmes
Subjects: 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Medicine, General Medicine, business, medicine.disease_cause, Virology, General Biochemistry, Genetics and Molecular Biology, Coronavirus
Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Published: 2020
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26. Comparison of different carotid stent designs in endovascular therapy of severe carotid artery stenosis

Author: Michael Diepers, Luca Remonda, Timo Kahles, Philipp Gruber, Krassen Nedeltchev, Jatta Berberat, and Javier Anon
Subjects: medicine.medical_specialty, medicine.medical_treatment, Carotid arteries, atherosclerotic, Neurosciences. Biological psychiatry. Neuropsychiatry, 030204 cardiovascular system & hematology, Endovascular therapy, 03 medical and health sciences, 0302 clinical medicine, carotid stenting, medicine, cardiovascular diseases, Thrombus, Stroke, business.industry, carotid artery, stent design, medicine.disease, stroke, hybrid carotid stent system, Stenosis, Embolism, Radiology, Carotid stenting, business, Stent design, 030217 neurology & neurosurgery, RC321-571, Double-layer micromesh stent
Abstract: One of the major periprocedural risks of carotid artery stenting is embolism caused either by plaque debris or by local thrombus forming. Double-layer micromesh stent design has shown to lower the chance of debris embolism but might have a slightly higher risk of local thrombus forming. Thus, we compared two different stent designs regarding safety and outcome profile in elective patients with high-grade carotid artery stenosis using a self-expanding, double-layer micromesh carotid stent system (DLCS) or a self-expanding hybrid carotid stent system (HCS). A single-center, open-label, retrospective cohort study of 67 consecutive, elective patients with high-grade symptomatic and asymptomatic carotid stenosis was executed at a comprehensive stroke center. Outcome measures were reocclusion rate, periprocedural symptomatic ischemic events, as well as other periprocedural complications, and recurrent stroke and mortality at 30 days&rsquo, follow-up. Thirty-two patients (24% women, median age 75 years (interquartile range (IQR) 71&ndash, 80) were treated with DLCS, and 35 patients (29% women, median age 71 years (IQR 63&ndash, 76) years) with HCS. In both groups, pretreatment carotid stenosis degree was similar (median NASCET of 80%). Successful deployment was achieved in all cases without technical failure, and both groups did not differ in reocclusion rates, recurrent stroke, and mortality within 30 days. DCLS and HCS revealed to have similar safety and outcome profile in elective patients with high-grade symptomatic as well as asymptomatic carotid artery stenosis.
Published: 2020
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27. Building an international consortium for tracking coronavirus health status

Author: Gary King, Gisel Booman, Alexandros Sigaras, Feng Zhang, Joshua Gale, Phil Ewels, Andrew T. Chan, Benjamin Geiger, Tim D. Spector, Jana Prodanova, Han Altae-Tran, André Kahles, Matej Orešič, Hagai Rossman, Casey S. Greene, Amir Gavrieli, Ophir Shalem, Roman Jerala, Eran Segal, Yonatan H. Grad, Svetlana Ovchinnikova, Long H. Nguyen, Xihong Lin, Aline Muller, Iman Hajirasouliha, Jay Rajagopal, Smadar Shilo, Silvano Coletti, Georgina Evans, Ori Cohen, Ran D. Balicer, Hedi Peterson, Tomer Meir, Ximena Bonilla, Natalie R. Davidson, Olli Kallioniemi, Paul Wilmes, David A. Drew, Ron Steinherz, Simon Anders, Tal Bauman, Gregory Landua, Jaak Vilo, Johan Rung, Ayya Keshet, Ljupco Kocarev, Gunnar Rätsch, Olivier Elemento, Yuval Dor, Irene Stevens, Andrea Sboner, William E. Allen, and Faisal Alquaddoomi
Subjects: 0301 basic medicine, 2019-20 coronavirus outbreak, Knowledge management, Coronavirus disease 2019 (COVID-19), Health Status, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Pneumonia, Viral, medicine.disease_cause, General Biochemistry, Genetics and Molecular Biology, Betacoronavirus, Databases, 03 medical and health sciences, 0302 clinical medicine, Computational platforms and environments, Surveys and Questionnaires, Research community, Pandemic, medicine, Humans, Pandemics, Coronavirus, SARS-CoV-2, business.industry, COVID-19, General Medicine, Publisher Correction, 030104 developmental biology, 030220 oncology & carcinogenesis, Infectious diseases, Tracking (education), Coronavirus Infections, business
Abstract: We call upon the research community to standardize efforts to use daily self-reported data about COVID-19 symptoms in the response to the pandemic and to form a collaborative consortium to maximize global gain while protecting participant privacy.
Published: 2020
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28. Sleep modulates hematopoiesis and protects against atherosclerosis

Author: Peter Libby, Vanessa Frodermann, Friedrich Felix Hoyer, Christoph J. Binder, Christopher T. Chan, Annemijn F. Gregory, Yoshiko Iwamoto, Anne Vassalli, Cameron S. McAlpine, Matthias Nahrendorf, Atsushi Anzai, Filip K. Swirski, Thomas E. Scammell, Shun He, Florian Kahles, Wolfram C. Poller, Ashley M. Fenn, Mehdi Tafti, John E. Mindur, Colin Valet, Sara Rattik, Lennard Halle, and M. Kiss
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, Lateral hypothalamus, Neutrophils, Bone Marrow Cells, Monocytes, Article, Mice, 03 medical and health sciences, 0302 clinical medicine, Monocytosis, Orexin Receptors, Internal medicine, mental disorders, medicine, Animals, Antigens, Ly, Antigens, Ly/metabolism, Atherosclerosis/metabolism, Atherosclerosis/pathology, Atherosclerosis/prevention & control, Bone Marrow Cells/metabolism, Female, Hematopoiesis/drug effects, Hematopoiesis/physiology, Hypothalamic Area, Lateral/metabolism, Monocytes/drug effects, Monocytes/metabolism, Myelopoiesis/drug effects, Neutrophils/metabolism, Orexin Receptors/deficiency, Orexin Receptors/metabolism, Orexins/biosynthesis, Orexins/deficiency, Orexins/metabolism, Orexins/pharmacology, Sleep/drug effects, Sleep/physiology, Sleep Deprivation/metabolism, Sleep Deprivation/physiopathology, Sleep Deprivation/prevention & control, Fragmentation (cell biology), Pathological, Myelopoiesis, Orexins, Multidisciplinary, business.industry, Macrophage Colony-Stimulating Factor, Atherosclerosis, medicine.disease, Sleep in non-human animals, Hematopoiesis, 3. Good health, Haematopoiesis, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, nervous system, Hypothalamic Area, Lateral, Sleep Deprivation, Bone marrow, Sleep, business, psychological phenomena and processes, 030217 neurology & neurosurgery
Abstract: Sleep is integral to life 1 . Although insufficient or disrupted sleep increases the risk of multiple pathological conditions, including cardiovascular disease 2 , we know little about the cellular and molecular mechanisms by which sleep maintains cardiovascular health. Here we report that sleep regulates haematopoiesis and protects against atherosclerosis in mice. We show that mice subjected to sleep fragmentation produce more Ly-6C high monocytes, develop larger atherosclerotic lesions and produce less hypocretin-a stimulatory and wake-promoting neuropeptide-in the lateral hypothalamus. Hypocretin controls myelopoiesis by restricting the production of CSF1 by hypocretin-receptor-expressing pre-neutrophils in the bone marrow. Whereas hypocretin-null and haematopoietic hypocretin-receptor-null mice develop monocytosis and accelerated atherosclerosis, sleep-fragmented mice with either haematopoietic CSF1 deficiency or hypocretin supplementation have reduced numbers of circulating monocytes and smaller atherosclerotic lesions. Together, these results identify a neuro-immune axis that links sleep to haematopoiesis and atherosclerosis.
Published: 2019

29. Self-reactive CD4+ IL-3+ T cells amplify autoimmune inflammation in myocarditis by inciting monocyte chemotaxis

Author: Kenneth Walsh, Matthias Nahrendorf, Shun He, Filip K. Swirski, John E. Mindur, Manfred Nairz, Lennard Halle, Sara Rattik, Soichi Sano, Jennifer L. Choi, Christopher T. Chan, De Lisa Fairweather, Florian Kahles, Ashley M. Fenn, Atsushi Anzai, Colin Valet, Yoshiko Iwamoto, Peter Libby, and Cameron S. McAlpine
Subjects: CD4-Positive T-Lymphocytes, 0301 basic medicine, Chemokine, Myocarditis, Monocyte chemotaxis, T cell, Immunology, Cardiomyopathy, Inflammation, medicine.disease_cause, Article, Monocytes, Autoimmune Diseases, Autoimmunity, Mice, 03 medical and health sciences, 0302 clinical medicine, medicine, Animals, Immunology and Allergy, Research Articles, Cell Proliferation, Mice, Knockout, Mice, Inbred BALB C, biology, business.industry, Effector, Chemotaxis, Macrophages, medicine.disease, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, biology.protein, Interleukin-3, medicine.symptom, business, 030215 immunology
Abstract: In autoimmune myocarditis, self-reactive T cells attack cardiac antigens and contribute to heart inflammation. In this study, Anzai et al. show that the T cell–derived cytokine and growth factor IL-3 amplifies inflammation and exacerbates autoimmune myocarditis., Acquisition of self-reactive effector CD4+ T cells is a major component of the autoimmune response that can occur during myocarditis, an inflammatory form of cardiomyopathy. Although the processes by which self-reactive T cells gain effector function have received considerable attention, how these T cells contribute to effector organ inflammation and damage is less clear. Here, we identified an IL-3–dependent amplification loop that exacerbates autoimmune inflammation. In experimental myocarditis, we show that effector organ–accumulating autoreactive IL-3+ CD4+ T cells stimulate IL-3R+ tissue macrophages to produce monocyte-attracting chemokines. The newly recruited monocytes differentiate into antigen-presenting cells that stimulate local IL-3+ CD4+ T cell proliferation, thereby amplifying organ inflammation. Consequently, Il3−/− mice resist developing robust autoimmune inflammation and myocardial dysfunction, whereas therapeutic IL-3 targeting ameliorates disease. This study defines a mechanism that orchestrates inflammation in myocarditis, describes a previously unknown function for IL-3, and identifies IL-3 as a potential therapeutic target in patients with myocarditis.
Published: 2019
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30. Building an International Consortium for Tracking Coronavirus Health Status

Author: Ximena Bonilla, Svetlana Ovchinnikova, William E. Allen, Iman Hajirasouliha, Tal Bauman, Andrea Sboner, Roman Jerala, Hedi Peterson, Matej Orešič, Hagai Rossman, Gary King, Ori Cohen, David A. Drew, Smadar Shilo, Silvano Coletti, Gunnar Rätsch, Joshua Gale, Casey S. Greene, Benjamin Geiger, Tomer Meir, Xihong Lin, Jay Rajagopal, Tim D. Spector, Olivier Elemento, Faisal Alquaddoomi, Yuval Dor, André Kahles, Alexandros Sigaras, Olli Kallioniemi, Amir Gavrieli, Feng Zhang, Irene Stevens, Long H. Nguyen, Ron Steinherz, Simon Anders, Johan Rung, Ayya Keshet, Georgina Evans, Phil Ewels, Natalie R. Davidson, Ophir Shalem, Yonatan H. Grad, Eran Segal, Aline Muller, Gregory Landua, Jaak Vilo, Paul Wilmes, Ran D. Balicer, Gisel Booman, and Andrew T. Chan
Subjects: education.field_of_study, Geospatial analysis, Knowledge management, business.industry, Control (management), Population, Globe, Disease, computer.software_genre, medicine.anatomical_structure, SPARK (programming language), Health care, Pandemic, medicine, business, education, computer, computer.programming_language
Abstract: Information is the most potent protective weapon we have to combat a pandemic, at both the individual and global level. For individuals, information can help us make personal decisions and provide a sense of security. For the global community, information can inform policy decisions and offer critical insights into the epidemic of COVID-19 disease. Fully leveraging the power of information, however, requires large amounts of data and access to it. To achieve this, we are making steps to form an international consortium, Coronavirus Census Collective (CCC, coronaviruscensuscollective.org), that will serve as a hub for integrating information from multiple data sources that can be utilized to understand, monitor, predict, and combat global pandemics. These sources may include self-reported health status through surveys (including mobile apps), results of diagnostic laboratory tests, and other static and real-time geospatial data. This collective effort to track and share information will be invaluable in predicting hotspots of disease outbreak, identifying which factors control the rate of spreading, informing immediate policy decisions, evaluating the effectiveness of measures taken by health organizations on pandemic control, and providing critical insight on the etiology of COVID-19. It will also help individuals stay informed on this rapidly evolving situation and contribute to other global efforts to slow the spread of disease.In the past few weeks, several initiatives across the globe have surfaced to use daily self-reported symptoms as a means to track disease spread, predict outbreak locations, guide population measures and help in the allocation of healthcare resources. The aim of this paper is to put out a call to standardize these efforts and spark a collaborative effort to maximize the global gain while protecting participant privacy.
Published: 2020
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31. Myocardial infarction is sufficient to increase GLP-1 secretion, leading to improved left ventricular contractility and mitochondrial respiratory capacity

Author: Elisa A. Liehn, Corinna Lebherz, Nikolaus Marx, Julia Moellmann, Florian Kahles, Michael Lehrke, S. Diebold, Alexander Nickel, Elias Haj-Yehia, and Christoph Maack
Subjects: Male, 0301 basic medicine, Cardiac function curve, endocrine system, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Cell Respiration, Myocardial Infarction, Hemodynamics, Linagliptin, 030204 cardiovascular system & hematology, Mitochondrion, Glucagon-Like Peptide-1 Receptor, Ventricular Function, Left, Contractility, Mice, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Glucagon-Like Peptide 1, Internal medicine, Internal Medicine, medicine, Animals, Secretion, cardiovascular diseases, Myocardial infarction, Dipeptidyl-Peptidase IV Inhibitors, business.industry, digestive, oral, and skin physiology, AMPK, medicine.disease, Myocardial Contraction, Mitochondria, Mice, Inbred C57BL, 030104 developmental biology, cardiovascular system, Cardiology, business, Ligation
Abstract: Myocardial infarction causes rapid impairment of left ventricular function and requires a hypercontractile response of non-infarcted tissue areas to maintain haemodynamic stability. This compensatory adaptation is mediated by humoral, inflammatory and neuronal signals. GLP-1 is an incretin hormone with glucoregulatory and cardioprotective capacities and is secreted in response to nutritional and inflammatory stimuli. Inactivation of GLP-1 is caused by the ubiquitously present enzyme DPP-4. In this study, circulating concentrations of GLP-1 were assessed after myocardial infarction and were evaluated in the light of metabolism, left ventricular contractility and mitochondrial function. Circulating GLP-1 concentrations were markedly increased in patients with acute myocardial infarction. Experimental myocardial infarction by permanent LAD ligation proved sufficient to increase GLP-1 secretion in mice. This took place in a time-dependent manner, which coincided with the capacity of DPP-4 inhibition, by linagliptin, to augment left ventricular contractility in a GLP-1 receptor-dependent manner. Mechanistically, DPP-4 inhibition increased AMPK activity and stimulated the mitochondrial respiratory capacity of non-infarcted tissue areas. We describe a new functional relevance of inflammatory GLP-1 secretion for left ventricular contractility during myocardial infarction.
Published: 2018
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32. Sekundärprävention des Schlaganfalls

Author: Smaila Mulic, Krassen Nedeltchev, and Timo Kahles
Subjects: medicine.medical_specialty, Percutaneous, business.industry, medicine.medical_treatment, MEDLINE, General Medicine, medicine.disease, Revascularization, Brain ischemia, medicine.anatomical_structure, medicine, Patent foramen ovale, Risk factor, Intensive care medicine, business, Stroke, Foramen ovale (heart)
Abstract: Zusammenfassung. Der Schlaganfall gehört zu den häufigsten Erkrankungen und ist die häufigste Ursache von bleibenden Behinderungen im Erwachsenenalter. Grundzüge der Sekundärprophylaxe des Schlaganfalls sind eine medikamentöse Therapie, Optimierung der modifizierbaren Risikofaktoren, die Revaskularisation einer symptomatischen Karotisstenosen sowie der Verschluss eines Persistierenden Foramen Ovale (bei Patienten unter 60 Jahren mit kryptogenem Schlaganfall).
Published: 2018
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33. Akuter Vorderwandinfarkt durch Koronarthrombus aufgrund eines spontanen Intimaeinrisses

Author: Sebastian Reith, Mathias Burgmaier, Nikolaus Marx, Florian Kahles, Michael Lehrke, and Alexander Schuh
Subjects: Gynecology, 03 medical and health sciences, medicine.medical_specialty, Acute coronary syndrome, 0302 clinical medicine, business.industry, medicine, 030212 general & internal medicine, General Medicine, 030204 cardiovascular system & hematology, medicine.disease, business
Abstract: Zusammenfassung Anamnese Wir berichten über einen adipösen 51-jährigen Patienten, der über plötzlich eintretende thorakale Schmerzen mit Ausstrahlung in den linken Arm klagt. Als kardiovaskuläre Risikofaktoren werden arterielle Hypertonie und Nikotinabusus angegeben. Untersuchungen Bei unauffälligem EKG-Befund, jedoch steigenden Troponinwerten (37 pg/ml; Norm Therapie Es erfolgt eine Implantation eines beschichteten Stents im Bereich des medialen RIVA sowie ein Loading mit Acetylsalicylsäure/Ticagrelor und eine Eptifibatid-Bolusgabe. Verlauf Nach Koronarintervention ist der Patient beschwerdefrei. Eine medikamentöse Therapie mittels ASS, Ticagrelor, Metoprolol und Simvastatin wird initiiert. Folgerung Dem Koronarthrombus des Patienten liegt eine spontane Koronardissektion (SCAD) im Bereich des medialen RIVA zugrunde. SCAD stellt eine wichtige Differenzialdiagnose des ACS dar, welche nach Möglichkeit mittels erweiterter bildgebender Diagnostik gesichert werden sollte. Leitlinienempfehlungen stehen aktuell noch aus.
Published: 2017
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34. Emergent vs. elective stenting of carotid stenosis with intraluminal carotid thrombus

Author: Krassen Nedeltchev, Javier Anon, Luca Remonda, Michael Diepers, Timo Kahles, Benjamin V. Ineichen, Martin Hlavica, and Jatta Berberat
Subjects: Male, medicine.medical_specialty, Neuroimaging, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Intraluminal thrombus, Carotid Stenosis, Radiology, Nuclear Medicine and imaging, cardiovascular diseases, Thrombus, Endovascular treatment, Aged, Retrospective Studies, Thrombectomy, Nihss score, Radiological and Ultrasound Technology, business.industry, Endovascular Procedures, Anticoagulants, Thrombosis, Patient data, Middle Aged, medicine.disease, Time optimal, Surgery, Mechanical thrombectomy, Stenosis, Treatment Outcome, Elective Surgical Procedures, cardiovascular system, Female, Stents, Neurology (clinical), Radiology, Emergencies, business, 030217 neurology & neurosurgery
Abstract: Background and purpose Carotid stenosis (CS) with intraluminal carotid artery thrombus (ICAT) is rare but ominous finding. The optimal treatment modality is unclear. The aim of this study was to analyze the feasibility and outcome of acute endovascular intervention and delayed elective endovascular therapy after initial anticoagulation in these delicate cases. Moreover, both treatment points were compared and several parameters discussed to facilitate the determination of the optimal time modality in future cases. Materials and methods A series of 11 consecutive cases with acute symptomatic CS with ICAT that received endovascular treatment was retrospectively analyzed. General patient data, pre and post-interventional symptoms and imaging were evaluated in an overall mean follow-up of 84 weeks. Results Urgent stenting and mechanical thrombectomy was performed in 6 patients. In the remaining 5 cases, elective endovascular treatment was planned after initial anticoagulation therapy with thrombus resolution. One case received secondary urgent treatment due to clinical deterioration. Overall outcome at three months follow-up was excellent (Modified Ranking Scale [mRS] 0–1) in 5 cases, good (mRS 2) in 4 and unfavorable in the remaining 2. Important differences between the two treatment arms were seen in 3 parameters (stenosis degree, thrombus length, and NIHSS score). Conclusions This is one of the largest studies analysing endovascular treatment in patients with acute symptomatic CS and additional ICAT only. Both endovascular treatment strategies seem feasible. Parameters such as size of intraluminal thrombus and clinical symptoms should be included in the decision-making process regarding the optimal individual treatment time.
Published: 2017
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35. The incretin hormone GIP decreases vascular infiltration and proinflammatory activation of monocytes in ApoE-/- mice

Author: Florian Kahles, Michael Lehrke, A Liberman, S. Diebold, Nikolaus Marx, M Burgmaier, Hannes M. Findeisen, Corinna Lebherz, M Julia, and C Halim
Subjects: medicine.medical_specialty, Endocrinology, Incretin Hormone, Apoe mice, business.industry, Endocrinology, Diabetes and Metabolism, Internal medicine, Immunology, medicine, medicine.disease, business, Infiltration (medical), Proinflammatory cytokine
Published: 2017
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36. Drug-Coated Balloon Treatment in Symptomatic Intracranial High Grade Stenosis : A Retrospective Study of 33 Patients

Author: Javier Anon, Timo Kahles, Michael Diepers, Jatta Berberat, Krassen Nedeltchev, Luca Remonda, and Philipp Gruber
Subjects: medicine.medical_specialty, Percutaneous, Constriction, Pathologic, Balloon, 030218 nuclear medicine & medical imaging, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Restenosis, Interquartile range, medicine, Humans, Radiology, Nuclear Medicine and imaging, Aged, Retrospective Studies, business.industry, Retrospective cohort study, medicine.disease, Intracranial Arteriosclerosis, Surgery, Stenosis, Pharmaceutical Preparations, Neurology (clinical), business, Complication, 030217 neurology & neurosurgery, Angioplasty, Balloon, Cohort study
Abstract: Endovascular therapy (EVT) represents an alternative treatment modality for symptomatic intracranial high-grade atherosclerotic stenosis (sICAS); however, periprocedural complication rates as well as midterm restenosis rates represent relevant limitations of EVT. Drug-coated balloon percutaneous transluminal angioplasty (DCB-PTA) may overcome some of these shortcomings. The aim of this study was to assess feasibility and safety as well as the stroke recurrence rate in 33 patients. A retrospective, monocentric cohort study of sICAS patients treated with DCB-PTA. Outcome measures were the periprocedural intracranial complication rate, the recurrent stroke rate and mortality during follow-up. This cohort study included 33 patients with 35 sICAS treated with DCB-PTA. The median age was 72 years (interquartile range, IQR 66–77 years); median clinical and mean radiological follow-up time was 9 months (IQR 3–22 months). Median preprocedural degree of stenosis (WASID) was 80% (IQR 73–80%) and median postprocedural residual stenosis degree (WASID) was 50% (IQR 33–60%). Intracranial periprocedural complications occurred in 2 (6%) patients. The overall restenosis rate was 15% (n = 5). In four patients a symptomatic ischemic re-event occurred within 7 months after the initial treatment. None of the patients died. This DCB-PTA cohort study showed a relatively low intracranial complication rate of 6% with a symptomatic recurrence rate of 12%. Larger trials are needed to validate these promising observations.
Published: 2020

37. Abstract WP225: Fetal-Type Posterior Cerebral Artery: A Not So Benign Anatomical Variant?

Author: Timo Kahles, Luca Remonda, Oliver Findling, Nadir Tissira, Nico Strecker, Philipp Gruber, Marta Kubacka, Krassen Nedeltchev, and Carlos Garcia Esperon
Subjects: Advanced and Specialized Nursing, Cerebral circulation, Fetus, business.industry, medicine.artery, medicine, Neurology (clinical), Posterior cerebral artery, Anatomy, Cardiology and Cardiovascular Medicine, medicine.disease, business, Stroke
Abstract: Introduction: The fetal-type of the posterior cerebral artery (ftPCA) is a remnant of the embryonic cerebral vasculature and describes a predominant supply of the PCA territory by a branch of the internal carotid artery. It is usually considered a benign anatomical variant with a prevalence ranging between 3% and 40%. Given the larger supply of the brain parenchyma by the anterior circulation in this variant, ftPCA is often associated with a hypoplastic basilar artery and thus a reduced vertebrobasilar blood flow. Hypothesis: Attenuated blood flow through the vertebrobasilar system in patients with a ftPCA is associated with an increased risk of infratentorial ischemic stroke. Methods: We prospectively analyzed 625 consecutive acute stroke patients from our comprehensive stroke center. Cerebral MRI was used to identify stroke location. PCA territory blood supply was classified in 5 subcategories using CT or MRI angiography: 1) total ftPCA (i.e. complete supply via PCOM); 2) predominant ftPCA; 3) balanced PCA (supply via PCOM and P1); 4) predominant P1, and 5) complete P1 supply. Variants 1) and 2) were considered ftPCA for further analysis. We compared the frequencies of anterior, posterior, infratentorial, and multiple territories strokes between patients with and without ftPCA. Results: There were 215 patients (34%) with ftPCA. Patients with ftPCA were significantly more likely to suffer from an infratentorial stroke than those without the ftPCA variant (20% vs 12.2%, P = 0.009). In contrast, anterior, posterior, and multiple territories stroke did not differ between groups. When posterior territory strokes were attributed to the corresponding P1 or PCOM supply, there was no difference in the frequency of vertebrobasilar stroke (i.e. infratentorial plus P1-PCA) between patients with and without ftPCA (P=0.864). Mean cross sectional area of the basilar artery was significantly lower in patients with ftPCA compared to those without ftPCA (6.6mm2 vs. 9.7mm2, P Conclusion: Fetal-type PCA is associated with a higher frequency of infratentorial stroke and a lower cross sectional area of the basilar artery. Possibly, hemodynamic factors influence infratentorial stroke risk in patients with ftPCA.
Published: 2020
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38. Butler enables rapid cloud-based analysis of thousands of human genomes

Author: Yakneen, Sergei, Waszak, Sebastian M, Gertz, Michael, Korbel, Jan O, Aminou, Brice, Bartolome, Javier, Boroevich, Keith A, Boyce, Rich, Brooks, Angela N, Buchanan, Alex, Buchhalter, Ivo, Butler, Adam P, Byrne, Niall J, Cafferkey, Andy, Campbell, Peter J, Chen, Zhaohong, Cho, Sunghoon, Choi, Wan, Clapham, Peter, Davis-Dusenbery, Brandi N, De La Vega, Francisco M, Demeulemeester, Jonas, Dow, Michelle T, Dursi, Lewis Jonathan, Eils, Juergen, Eils, Roland, Ellrott, Kyle, Farcas, Claudiu, Favero, Francesco, Fayzullaev, Nodirjon, Ferretti, Vincent, Flicek, Paul, Fonseca, Nuno A, Gelpi, Josep Ll, Getz, Gad, Gibson, Bob, Grossman, Robert L, Harismendy, Olivier, Heath, Allison P, Heinold, Michael C, Hess, Julian M, Hofmann, Oliver, Hong, Jongwhi H, Hudson, Thomas J, Hutter, Barbara, Hutter, Carolyn M, Huebschmann, Daniel, Imoto, Seiya, Ivkovic, Sinisa, Jeon, Seung-Hyup, Jiao, Wei, Jung, Jongsun, Kabbe, Rolf, Kahles, Andre, Kerssemakers, Jules NA, Kim, Hyung-Lae, Kim, Hyunghwan, Kim, Jihoon, Kim, Youngwook, Kleinheinz, Kortine, Koscher, Michael, Koures, Antonios, Kovacevic, Milena, Lawerenz, Chris, Leshchiner, Ignaty, Liu, Jia, Livitz, Dimitri, Mihaiescu, George L, Mijalkovic, Sanja, Lazic, Ana Mijalkovic, Miyano, Satoru, Miyoshi, Naoki, Nahal-Bose, Hardeep K, Nakagawa, Hidewaki, Nastic, Mia, Newhouse, Steven J, Nicholson, Jonathan, O'Connor, Brian D, Ocana, David, Ohi, Kazuhiro, Ohno-Machado, Lucila, Omberg, Larsson, Ouellette, BF Francis, Paramasivam, Nagarajan, Perry, Marc D, Pihl, Todd D, Prinz, Manuel, Puiggros, Montserrat, Radovic, Petar, Raine, Keiran M, Rheinbay, Esther, Rosenberg, Mara, Royo, Romina, Raetsch, Gunnar, Saksena, Gordon, Schlesner, Matthias, Shorser, Solomon, Short, Charles, Sofia, Heidi J, Spring, Jonathan, Stein, Lincoln D, Struck, Adam J, Tiao, Grace, Tijanic, Nebojsa, Torrents, David, Van Loo, Peter, Vazquez, Miguel, Vicente, David, Wala, Jeremiah A, Wang, Zhining, Weischenfeldt, Joachim, Werner, Johannes, Williams, Ashley, Woo, Youngchoon, Wright, Adam J, Xiang, Qian, Yang, Liming, Yuen, Denis, Yung, Christina K, Zhang, Junjun, Graduate School, Laboratory Genetic Metabolic Diseases, AGEM - Endocrinology, metabolism and nutrition, and AGEM - Inborn errors of metabolism
Subjects: Computer science, Biomedical Engineering, Bioengineering, Cloud computing, computer.software_genre, Brief Communication, Genome informatics, Genoma humà, Applied Microbiology and Biotechnology, Genome, Biologia computacional, Computational biology, 03 medical and health sciences, 0302 clinical medicine, Software, Computational platforms and environments, Cancer genome, Neoplasms, Humans, Hardware and infrastructure, ddc:610, 030304 developmental biology, VARIANT DISCOVERY, 0303 health sciences, Data processing, Science & Technology, Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], Human genome, business.industry, Genome, Human, Computational Biology, Cloud Computing, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], Biotechnology & Applied Microbiology, Molecular Medicine, Anomaly detection, Data mining, business, computer, Life Sciences & Biomedicine, 030217 neurology & neurosurgery, Biotechnology
Abstract: Cloud computing offers easy and economical access to computational capacity at a scale that had previously been available to only the largest research institutions. To take advantage, large biological datasets are increasingly analyzed on various cloud computing platforms, using public, private and hybrid clouds1 with the aid of workflow systems. When employed in global projects, such systems must be flexible in their ability to operate in different environments, including academic clouds, to allow researchers to bring their computational pipelines to the data, especially in cases where the raw data themselves cannot be moved. The recently developed cloud-based scientific workflow frameworks Nextflow2, Toil3 and GenomeVIP4 focus their support largely on individual commercial cloud computing environments—mostly Amazon Web Services—and lack complete functionality for other major providers. This limits their use in studies that require multi-cloud operation due to practical and regulatory requirements5,6. Butler, in contrast, provides full support for operation on OpenStack-based commercial and academic clouds, Amazon Web Services, Microsoft Azure and Google Compute Platform, and can thus enable international collaborations involving the analysis of hundreds of thousands of samples where distributed cloud-based computation is pursued in different jurisdictions5,6,7., Nature Biotechnology, 38 (3), ISSN:1546-1696, ISSN:1087-0156
Published: 2020
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39. Prior Stroke in PFO Patients Is Associated With Both PFO-Related and -Unrelated Factors

Author: Timo Kahles, Patrik Michel, Alexander Hapfelmeier, Franz R. Eberli, Marialuisa Zedde, Vincent Thijs, Markus Kraemer, Stefan T. Engelter, Joaquin Serena, Christian Weimar, Achim Mallmann, Andreas Luft, Dimitri Hemelsoet, David E. Thaler, Andreas Müller-Eichelberg, Adinda De Pauw, Roman Sztajzel, Carmel Armon, David M. Kent, Bernhard Meier, Heinrich P. Mattle, Urs Fischer, Marcel Arnold, Marie-Luise Mono, Krassen Nedeltchev, for the International PFO Consortium NCT00859885, and International PFO Consortium NCT00859885
Subjects: medicine.medical_specialty, RECURRENT CEREBRAL-ISCHEMIA, patent foramen ovale, medicine.medical_treatment, Right-to-left shunt, Clinical Neurology, prior stroke, Medizin, 610 Medicine & health, 030204 cardiovascular system & hematology, lcsh:RC346-429, International PFO Consortium, MEDICAL THERAPY, PFO, cryptogenic stroke, hypercholesterolemia, right-to-left shunt, risk factor, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, medicine.artery, Internal medicine, Medicine and Health Sciences, medicine, Valsalva maneuver, ATTACK, cardiovascular diseases, METAANALYSIS, lcsh:Neurology. Diseases of the nervous system, Original Research, OLDER, RISK, CRYPTOGENIC STROKE, business.industry, Odds ratio, medicine.disease, PERCUTANEOUS CLOSURE, Pulmonary embolism, Venous thrombosis, Neurology, Patent foramen ovale, Cardiology, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Background and Purpose: To identify factors associated with prior stroke at presentation in patients with cryptogenic stroke (CS) and patent foramen ovale (PFO). Methods: We studied cross-sectional data from the International PFO Consortium Study (NCT00859885). Patients with first-ever stroke and those with prior stroke at baseline were analyzed for an association with PFO-related (right-to-left shunt at rest, atrial septal aneurysm, deep venous thrombosis, pulmonary embolism, and Valsalva maneuver) and PFO-unrelated factors (age, gender, BMI, hypertension, diabetes mellitus, hypercholesterolemia, smoking, migraine, coronary artery disease, aortic plaque). A multivariable analysis was used to adjust effect estimation for confounding, e.g., owing to the age-dependent definition of study groups in this cross-sectional study design. Results: We identified 635 patients with first-ever and 53 patients with prior stroke. Age, BMI, hypertension, diabetes mellitus, hypercholesterolemia, coronary artery disease, and right-to-left shunt (RLS) at rest were significantly associated with prior stroke. Using a pre-specified multivariable logistic regression model, age (Odds Ratio 1.06), BMI (OR 1.06), hypercholesterolemia (OR 1.90) and RLS at rest (OR 1.88) were strongly associated with prior stroke.Based on these factors, we developed a nomogram to illustrate the strength of the relation of individual factors to prior stroke. Conclusion: In patients with CS and PFO, the likelihood of prior stroke is associated with both, PFO-related and PFO-unrelated factors. CA extern
Published: 2020
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40. P1757GLP-1 levels predict cardiovascular risk in patients with acute myocardial infarction

Author: Florian Kahles, Michael Lehrke, M V Rueckbeil, Evangelos Giannitsis, Julia Moellmann, Nikolaus Marx, R W Mertens, M C Arrivas, M C Biener, Hugo A. Katus, Corinna Lebherz, and Ann Christina Foldenauer
Subjects: medicine.medical_specialty, business.industry, Internal medicine, medicine, Cardiology, In patient, Myocardial infarction, Cardiology and Cardiovascular Medicine, medicine.disease, business, hormones, hormone substitutes, and hormone antagonists
Abstract: Background Glucagon-like peptide 1 (GLP-1) is a gut incretin hormone, which induces post-prandial glucose-dependent insulin secretion. GLP-1 receptor agonists improve cardiovascular outcomes in patients with diabetes at high cardiovascular risk. We recently found GLP-1 levels to be increased in patients with acute myocardial infarction. Purpose The aim of this study was to assess the predictive capacity of GLP-1 for cardiovascular outcome in patients with myocardial infarction. Methods Total GLP-1 levels, NT-proBNP concentrations and the Global Registry of Acute Coronary Events (GRACE) score were assessed at time of admission in 918 patients with myocardial infarction presenting with acute chest pain. Among these 597 patients presented with NSTEMI and 321 with STEMI. The primary composite outcome of the study was the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke with a median follow-up of 311 days. Results Kaplan-Meier survival plots (separated by tertiles with cut-off values 35.44 and 53.45) and univariate cox regression analyses found GLP-1 values to be associated with adverse outcome (combined endpoint and all-cause mortality) (logarithmized GLP-1 values HR: 5.459; p Conclusion GLP-1 is a new biomarker of cardiovascular risk and adverse outcomes in patients with acute myocardial infarction and improves the predictive value of the GRACE score in patients with NSTEMI.
Published: 2019
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41. Angioplasty Using Drug-Coated Balloons in Ostial Vertebral Artery Stenosis

Author: Javier Anon, Timo Kahles, Luca Remonda, Michael Diepers, Krassen Nedeltchev, Jatta Berberat, and Philipp Gruber
Subjects: Male, medicine.medical_specialty, Percutaneous, Time Factors, Databases, Factual, medicine.medical_treatment, 030204 cardiovascular system & hematology, Balloon, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Restenosis, Coated Materials, Biocompatible, Angioplasty, medicine, Vertebrobasilar Insufficiency, Vascular Patency, Humans, Stroke, Aged, Retrospective Studies, business.industry, Retrospective cohort study, General Medicine, Equipment Design, Middle Aged, medicine.disease, Surgery, Dissection, Treatment Outcome, Feasibility Studies, Female, Cardiology and Cardiovascular Medicine, business, Angioplasty, Balloon, Vascular Access Devices
Abstract: Background Ostial vertebral artery stenosis (OVAS) is a relevant cause of acute ischemic posterior circulation stroke. Percutaneous trans-luminal angioplasty (PTA) might offer a promising treatment modality, but restenosis rate is high. So far, little is known about recanalization using drug-coated balloons (DCB) in OVAS. We aimed to show feasibility and safety of DCB-PTA in OVAS. Methods Retrospective, monocenter case series of 12 patients with ostial vertebral artery stenosis (≥50%) treated with PTA using a drug-coated balloon. Results Median age was 69.5 years (IQR 57–78.5) with a female rate of 41%. Patients were treated either with a SeQuent Please NEO or Neuro Elutax SV DEB. Median preinterventional stenosis degree was 75% (IQR 70–85) with a median lesion length of 4.5 mm (IQR 4–7.5). Median postinterventional stenosis degree was 40% (IQR 27–50). All treated vessels remained patent. No major complications such as dissection, vessel perforation, hemorrhage, or ischemic events occurred. Moreover, we did not detect any restenosis during a median follow-up period of 6.1 months. The clinical outcome was excellent with median mRS scale of 0 (IQR 0–1). Conclusions PTA using drug-coated balloons is feasible and safe in patients with ostial vertebral artery stenosis.
Published: 2019

42. Glucagon-like peptide 1 levels predict cardiovascular risk in patients with acute myocardial infarction

Author: Hugo A. Katus, Florian Kahles, Michael Lehrke, Moritz Biener, M C Arrivas, Ann Christina Foldenauer, Julia Moellmann, Nikolaus Marx, R W Mertens, Marcia Viviane Rückbeil, Evangelos Giannitsis, Corinna Lebherz, and Publica
Subjects: medicine.medical_specialty, medicine.drug_class, Myocardial Infarction, Incretin, Renal function, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Glucagon-Like Peptide 1, Risk Factors, Internal medicine, Diabetes mellitus, Natriuretic Peptide, Brain, medicine, Natriuretic peptide, Humans, 030212 general & internal medicine, Myocardial infarction, Stroke, business.industry, Proportional hazards model, Hazard ratio, medicine.disease, Prognosis, Peptide Fragments, Cardiovascular Diseases, Heart Disease Risk Factors, Cardiology, Cardiology and Cardiovascular Medicine, business, Biomarkers
Abstract: Aims Glucagon-like peptide 1 (GLP-1) is a gut incretin hormone inducing post-prandial insulin secretion. Glucagon-like peptide 1 levels were recently found to be increased in patients with acute myocardial infarction. Glucagon-like peptide 1 receptor agonists improve cardiovascular outcomes in patients with diabetes. The aim of this study was to assess the predictive capacity of GLP-1 serum levels for cardiovascular outcome in patients with myocardial infarction. Methods and results In 918 patients presenting with myocardial infarction [321 ST-segment elevation myocardial infarction and 597 non-ST-segment elevation myocardial infarction (NSTEMI)] total GLP-1, N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and the Global Registry of Acute Coronary Events (GRACE) score were assessed at time of hospital admission. The primary composite outcome of the study was the first occurrence of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke. Kaplan–Meier survival plots and univariable Cox regression analyses found GLP-1 to be associated with adverse outcome [hazard ratio (HR) of logarithmized GLP-1 values: 6.29, 95% confidence interval (CI): 2.67–14.81; P < 0.0001]. After further adjustment for age, sex, family history of cardiovascular disease, smoking, diabetes, hypertension, hypercholesterinaemia, glomerular filtration rate (GFR) CKD-EPI, hs-CRP, hs-Troponin T, and NT-proBNP levels the HR remained significant at 10.98 (95% CI: 2.63–45.90; P = 0.0010). Time-dependent receiver operating characteristic curve analyses illustrated that GLP-1 levels are a strong indicator for early events. For events up to 30 days after admission, GLP-1 proved to be superior to other biomarkers including hs-Troponin T, GFR CKD-EPI, hs-CRP, and NT-proBNP. Adjustment of the GRACE risk estimate by addition of GLP-1 increased the area under the receiver operating characteristic curve over time in NSTEMI patients. Conclusion In patients hospitalized for myocardial infarction, GLP-1 levels are associated with cardiovascular events.
Published: 2019

43. Automating Root Cause Analysis via Machine Learning in Agile Software Testing Environments

Author: Alexander Jung, Julen Kahles, Juha Torronen, Timo Huuhtanen, Ericsson Finland, Department of Computer Science, Helsinki Institute for Information Technology (HIIT), Aalto-yliopisto, and Aalto University
Subjects: Root (linguistics), Computer science, 02 engineering and technology, Software prototyping, Machine learning, computer.software_genre, Clustering, Software testing, Automation, 0202 electrical engineering, electronic engineering, information engineering, Root cause analysis, Adaptation (computer science), Cluster analysis, ta113, Artificial neural network, Artificial neural networks, Log data analysis, business.industry, 020207 software engineering, Classification, 020201 artificial intelligence & image processing, Artificial intelligence, business, computer, Agile software development
Abstract: We apply machine learning to automate the root cause analysis in agile software testing environments. In particular, we extract relevant features from raw log data after interviewing testing engineers (human experts). Initial efforts are put into clustering the unlabeled data, and despite obtaining weak correlations between several clusters and failure root causes, the vagueness in the rest of the clusters leads to the consideration of labeling. A new round of interviews with the testing engineers leads to the definition of five ground-truth categories. Using manually labeled data, we train artificial neural networks that either classify the data or pre-process it for clustering. The resulting method achieves an accuracy of 88.9%. The methodology of this paper serves as a prototype or baseline approach for the extraction of expert knowledge and its adaptation to machine learning techniques for root cause analysis in agile environments.
Published: 2019

44. Improving the post-acute care discharge score (PACD) by adding patients' self-care abilities: A prospective cohort study

Author: Koch, Daniel, Schuetz, Philipp, Haubitz, Sebastian, Kutz, Alexander, Mueller, Beat, Weber, Helen, Regez, Katharina, Conca, Antoinette, Hausfater, Pierre, Amin, Devendra, Faessler, Lukas, Grolimund, Eva, Schild, Ursula, Caldara, Zeljka, Zhydkov, Andriy, Kahles, Timo, Nedeltchev, Krassen, von Felten, Stefanie, De Geest, Sabina, Schaefer-Keller, Petra, Huber, Andreas, Bargetzi, Mario, Buergi, Ulrich, Sauvin, Gabrielle, Perrig-Chiello, Pasqualina, and Reutlinger, Barbara
Subjects: Male, Multivariate analysis, PREDICTION, Logistic regression, 0302 clinical medicine, Cognition, Risk Factors, Health care, Clinical endpoint, Medicine and Health Sciences, Public and Occupational Health, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Geriatrics, Cognitive Impairment, Aged, 80 and over, Multidisciplinary, Cognitive Neurology, Middle Aged, Hospitals, Patient Discharge, 3. Good health, Hospitalization, Multidisciplinary Sciences, Neurology, Medicine, Science & Technology - Other Topics, Female, Subacute Care, Research Article, medicine.medical_specialty, Patients, Science, Cognitive Neuroscience, Disabilities, 03 medical and health sciences, Diagnostic Medicine, medicine, Humans, Aged, Inpatients, Science & Technology, Receiver operating characteristic, business.industry, Biology and Life Sciences, 030208 emergency & critical care medicine, Health Care, Self Care, MODEL, Health Care Facilities, Emergency medicine, Cognitive Science, Observational study, business, Neuroscience
Abstract: BACKGROUND: Reducing delays in hospital discharge is important to improve transition processes and reduce health care costs. The recently proposed post-acute care discharge score focusing on the self-care abilities before hospital admission allows early identification of patients with a need for post-acute care. New limitations in self-care abilities identified during hospitalization may also indicate a risk. Our aim was to investigate whether the addition of the post-acute care discharge score and a validated self-care instrument would improve the prognostic accuracy to predict post-acute discharge needs in unselected medical inpatients. METHODS: We included consecutive adult medical and neurological inpatients. Logistic regression models with area under the receiver operating characteristic curve were calculated to study associations of post-acute discharge score and self-care index with post-acute discharge risk. We calculated joint regression models and reclassification statistics including the net reclassification index and integrated discrimination improvement to investigate whether merging the self-care index and the post-acute discharge score leads to better diagnostic accuracy. RESULTS: Out of 1342 medical and 402 neurological patients, 150 (11.18%) and 94 (23.38%) have reached the primary endpoint of being discharged to a post-acute care facility. Multivariate analysis showed that the self-care index is an outcome predictor (OR 0.897, 95%CI 0.864-0.930). By combining the self-care index and the post-acute care discharge score discrimination for medical (from area under the curve 0.77 to 0.83) and neurological patients (from area under the curve 0.68 to 0.78) could be significantly improved. Reclassification statistics also showed significant improvements with regard to net reclassification index (14.2%, p
Published: 2019

45. The PDE4 inhibitor roflumilast reduces weight gain by increasing energy expenditure and leads to improved glucose metabolism

Author: Christian Werner, Corinna Lebherz, Julia Möllmann, Ben Arpad Kappel, Nikolaus Marx, Massimo Federici, Frank Tacke, Florian Kahles, Michael Lehrke, and Christer Baeck
Subjects: 0301 basic medicine, medicine.medical_specialty, biology, business.industry, Endocrinology, Diabetes and Metabolism, Carbohydrate metabolism, medicine.disease, CREB, 03 medical and health sciences, 030104 developmental biology, Endocrinology, Insulin resistance, Mitochondrial biogenesis, Weight loss, Internal medicine, Internal Medicine, medicine, biology.protein, Steatohepatitis, medicine.symptom, business, Receptor, Roflumilast, medicine.drug
Abstract: Aims To investigate the metabolic effects of the phosphodiesterase-4 (PDE4) inhibitor roflumilast, a clinically approved anti-inflammatory drug used for the treatment of chronic obstructive pulmonary disease. Materials and methods The metabolic effects of roflumilast were investigated in C57BL/6J mice, fed a high-fat Western-type diet and treated with or without roflumilast for a period of 12 weeks. Results Roflumilast led to a marked reduction in body weight gain, which became apparent in the second week after treatment initiation and was attributable to a pronounced increase in energy expenditure. Furthermore, roflumilast improved glucose tolerance, reduced insulin resistance and diminished steatohepatitis in mice. Mechanistically, this was associated with hepatic protein kinase A (PKA) and cAMP response element binding protein (CREB) activation, leading to peroxisome proliferator-activated receptor gamma coactivator-1α (PCG-1α)-dependent induction of mitochondrial biogenesis. Consistently, roflumilast increased the cellular respiratory capacity of hepatocytes in a PKA-dependent manner. Conclusion Roflumilast-dependent PDE4 inhibition is a new target for weight loss strategies, especially in conditions of associated comorbidities such as insulin resistance and non-alcoholic steatohepatitis.
Published: 2017
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46. In vivo quantification of amyloid burden in TTR-related cardiac amyloidosis

Author: Christoph Röcken, Felix M. Mottaghy, Mathias Burgmaier, Sebastian Reith, Florian Kahles, Svetlana Kintsler, Ruth Knüchel, Sandra Hamada, Alexander Marco Kollikowski, and Nikolaus Marx
Subjects: medicine.medical_specialty, biology, medicine.diagnostic_test, Amyloid, business.industry, Amyloidosis, Cardiomyopathy, General Medicine, 030204 cardiovascular system & hematology, medicine.disease, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Transthyretin, 0302 clinical medicine, Cardiac amyloidosis, In vivo, Cardiac magnetic resonance imaging, Biopsy, biology.protein, Medicine, Radiology, business
Abstract: Cardiac transthyretin-related (ATTR) amyloidosis is a severe cardiomyopathy for which therapeutic approaches are currently under development. Because non-invasive imaging techniques such as cardiac magnetic resonance imaging and echocardiography are non-specific, the diagnosis of ATTR amyloidosis is still based on myocardial biopsy. Thus, diagnosis of ATTR amyloidosis is difficult in patients refusing myocardial biopsy. Furthermore, myocardial biopsy does not allow 3D-mapping and quantification of myocardial ATTR amyloid. In this report we describe a 99mTc-DPD-based molecular imaging technique for non-invasive single-step diagnosis, three-dimensional mapping and semiquantification of cardiac ATTR amyloidosis in a patient with suspected amyloid heart disease who initially rejected myocardial biopsy. This report underlines the clinical value of SPECT-based nuclear medicine imaging to enable non-invasive diagnosis of cardiac ATTR amyloidosis, particularly in patients rejecting biopsy.
Published: 2017
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47. Glucose-dependent insulinotropic peptide secretion is induced by inflammatory stimuli in an interleukin-1-dependent manner in mice

Author: Ann Christina Foldenauer, Corinna Lebherz, S. Diebold, Julia Möllmann, Florian Kahles, Michael Lehrke, Christina Meyer, Hannes M. Findeisen, Robert Stöhr, and Nikolaus Marx
Subjects: Blood Glucose, Lipopolysaccharides, Male, 0301 basic medicine, endocrine system, medicine.medical_specialty, Lipopolysaccharide, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Interleukin-1beta, Incretin, Inflammation, Gastric Inhibitory Polypeptide, Proinflammatory cytokine, Mice, 03 medical and health sciences, chemistry.chemical_compound, Endocrinology, Gastric inhibitory polypeptide, Internal medicine, Internal Medicine, Animals, Medicine, Secretion, Mice, Knockout, Receptors, Interleukin-1 Type I, Interleukin-6, business.industry, Insulin, Interleukin, Up-Regulation, Mice, Inbred C57BL, 030104 developmental biology, chemistry, medicine.symptom, business, hormones, hormone substitutes, and hormone antagonists
Abstract: Recently, glucagon-like peptide-1 (GLP-1) levels have been found to be increased in response to inflammatory stimuli, leading to insulin secretion and prevention of hyperglycaemia during endotoxemia in mice. In the present study, we assess the relevance of the other incretin hormone, glucose-dependent insulinotropic peptide (GIP), as a regulator of glucose metabolism under inflammatory conditions. We found that lipopolysaccharide (LPS) increased GIP secretion in a time- and dose-dependent manner in C57BL/6J mice. To elucidate the underlying mechanisms, mice were injected with inflammatory cytokines known to be released by LPS. Circulating GIP levels significantly increased in response to interleukin (IL)-1β but not IL-6 or tumour necrosis factor (TNF)-α administration. Using respective knockout mice we found that LPS-mediated GIP secretion was selectively dependent on IL-1 signalling. To evaluate the functional relevance of inflammatory GIP secretion we pretreated mice with the GIP-receptor antagonist (Pro3)GIP. This blunted LPS-induced TNF-α and IL-6 secretion but did not affect LPS-induced insulin secretion or blood glucose-lowering. In conclusion, GIP provides a novel link between the immune system and the gut, with proinflammatory-immune modulatory function but minor glucose regulatory relevance in the context of acute endotoxemia.
Published: 2016
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48. Immunmodulierende Wirkung von Vitamin D und Typ-1-Diabetes

Author: H. Kahles
Subjects: 0301 basic medicine, Gynecology, 03 medical and health sciences, medicine.medical_specialty, 030104 developmental biology, 0302 clinical medicine, business.industry, Endocrinology, Diabetes and Metabolism, medicine, 030209 endocrinology & metabolism, business
Abstract: Vitamin D ist nicht nur fur Knochen essenziell. Es gibt viele Hinweise auf seine additive, immunmodulierende Wirkung, die moglicherweise Einfluss auf die Pathogenese verschiedener Autoimmunerkrankungen nehmen kann. Seine vielschichtigen Aufgaben innerhalb des Immunsystems sind noch nicht vollstandig verstanden, und die Studienresultate sind teilweise inkongruent. Insgesamt ergeben sich aber aus Sicht des Autors berechtigte Hoffnungen auf neue Therapieansatze fur Erkrankungen wie Diabetes mellitus Typ 1. Der vorliegende Beitrag soll einen Uberblick uber die Effekte und Empfehlungen von Vitamin-D-Substitutionen geben, insbesondere in Bezug auf nichtklassische Effekte. Sowohl im Tiermodell als auch aus epidemiologischen Untersuchungen beim Menschen ergaben sich Belege fur eine protektive Potenz von Vitamin D bezuglich der Manifestation eines Diabetes mellitus Typ 1. Trotz der vielen Hinweise auf eine gunstige Beeinflussung endokrinologischer Erkrankungen durch Vitamin D konnten hierfur in klinischen Studien noch keine harten Belege gefunden werden. Dementsprechend gibt es noch keine Empfehlung fur eine Vitamin-D-Substitution in Bezug auf diese nichtklassischen Funktionen. Ein Vitamin-D-Mangel sollte jedoch vermieden werden, insbesondere in fruhen Lebensjahren und bei familiarem Risiko fur entsprechende Erkrankungen.
Published: 2016
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49. Penumbral imaging and functional outcome in patients with anterior circulation ischaemic stroke treated with endovascular thrombectomy versus medical therapy: a meta-analysis of individual patient-level data

Author: Bruce C V Campbell, Charles B L M Majoie, Gregory W Albers, Bijoy K Menon, Nawaf Yassi, Gagan Sharma, Wim H van Zwam, Robert J van Oostenbrugge, Andrew M Demchuk, Francis Guillemin, Philip White, Antoni Dávalos, Aad van der Lugt, Kenneth S Butcher, Aboubaker Cherifi, Henk A Marquering, Geoffrey Cloud, Juan M Macho Fernández, Jeremy Madigan, Catherine Oppenheim, Geoffrey A Donnan, Yvo B W E M Roos, Jai Shankar, Hester Lingsma, Alain Bonafé, Hélène Raoult, María Hernández-Pérez, Aditya Bharatha, Reza Jahan, Olav Jansen, Sébastien Richard, Elad I Levy, Olvert A Berkhemer, Marc Soudant, Lucia Aja, Stephen M Davis, Timo Krings, Marie Tisserand, Luis San Román, Alejandro Tomasello, Debbie Beumer, Scott Brown, David S Liebeskind, Serge Bracard, Keith W Muir, Diederik W J Dippel, Mayank Goyal, Jeffrey L Saver, Tudor G Jovin, Michael D Hill, Peter J Mitchell, Puck SS Fransen, Lucie A van den Berg, Hester F Lingsma, Albert J Yoo, Wouter J Schonewille, Jan Albert Vos, Paul J Nederkoorn, Marieke JH Wermer, Marianne AA van Walderveen, Julie Staals, Jeannette Hofmeijer, Jacques A. van Oostayen, Geert J. Lycklama à Nijeholt, Jelis Boiten, Patrick A. Brouwer, Bart J. Emmer, Sebastiaan F. de Bruijn, Lukas C. van Dijk, Jaap Kappelle, Rob H Lo, Ewoud J. van Dijk, Joost de Vries, Paul L.M. de Kort, Willem Jan J. van Rooij, Jan S.P. van den Berg, Boudewijn A.A.M. van Hasselt, Leo A.M. Aerden, René J. Dallinga, Marieke C. Visser, Joseph C.J. Bot, Patrick C. Vroomen, Omid Eshghi, Tobien H.C.M.L. Schreuder, Roel J.J. Heijboer, Koos Keizer, Alexander V. Tielbeek, Heleen M. den Hertog, Dick G. Gerrits, Renske M. van den Berg-Vos, Giorgos B. Karas, Ewout W. Steyerberg, Zwenneke Flach, Henk A. Marquering, Marieke E.S. Sprengers, Sjoerd F.M. Jenniskens, Ludo F.M. Beenen, René van den Berg, Peter J. Koudstaal, Wim H. van Zwam, Yvo B.W.E.M. Roos, Robert J. van Oostenbrugge, Charles B.L.M. Majoie, Diederik W.J. Dippel, Martin M. Brown, Thomas Liebig, Theo Stijnen, Tommy Andersson, Heinrich Mattle, Nils Wahlgren, Esther van der Heijden, Naziha Ghannouti, Nadine Fleitour, Imke Hooijenga, Corina Puppels, Wilma Pellikaan, Annet Geerling, Annemieke Lindl-Velema, Gina van Vemde, Ans de Ridder, Paut Greebe, José de Bont-Stikkelbroeck, Joke de Meris, Kirsten Janssen, Willy Struijk, Silvan Licher, Nikki Boodt, Adriaan Ros, Esmee Venema, Ilse Slokkers, Raymie-Jayce Ganpat, Maxim Mulder, Nawid Saiedie, Alis Heshmatollah, Stefanie Schipperen, Stefan Vinken, Tiemen van Boxtel, Jeroen Koets, Merel Boers, Emilie Santos, Jordi Borst, Ivo Jansen, Manon Kappelhof, Marit Lucas, Ralph Geuskens, Renan Sales Barros, Roeland Dobbe, Marloes Csizmadia, MD Hill, M Goyal, AM Demchuk, BK Menon, M Eesa, KJ Ryckborst, MR Wright, NR Kamal, L Andersen, PA Randhawa, T Stewart, S Patil, P Minhas, M Almekhlafi, S Mishra, F Clement, T Sajobi, A Shuaib, WJ Montanera, D Roy, FL Silver, TG Jovin, DF Frei, B Sapkota, JL Rempel, J Thornton, D 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Parsons, Ferdinand Miteff, Christopher R Levi, Timothy Ang, Neil Spratt, Lara Kaauwai, Monica Badve, Henry Rice, Laetitia de Villiers, P. Alan Barber, Ben McGuinness, Ayton Hope, Maurice Moriarty, Patricia Bennett, Andrew Wong, Alan Coulthard, Andrew Lee, Jim Jannes, Deborah Field, Simon Salinas, Elise Cowley, Barry Snow, John Kolbe, Richard Stark, John King, Richard Macdonnell, John Attia, Cate D'Este, Hans-Christoph Diener, Elad I. Levy, Vitor Mendes Pereira, Gregory W. Albers, Christophe Cognard, David J. Cohen, Werner Hacke, Tudor G. Jovin, Heinrich P. Mattle, Raul G. Nogueira, Adnan H. Siddiqui, Dileep R. Yavagal, Rüdiger von Kummer, Wade Smith, Francis Turjman, Scott Hamilton, Richard Chiacchierini, Arun Amar, Nerses Sanossian, Yince Loh, B Baxter, VK Reddy, A Horev, M Star, A Siddiqui, LN Hopkins, K Snyder, R Sawyer, S Hall, V Costalat, C Riquelme, P Machi, E Omer, C Arquizan, I Mourand, M Charif, X Ayrignac, N Menjot de Champfleur, N Leboucq, G Gascou, M Moynier, R du Mesnil de Rochemont, O Singer, J Berkefeld, C Foerch, M Lorenz, W Pfeilschifer, E Hattingen, M Wagner, SJ You, S Lescher, H Braun, S Dehkharghani, SR Belagaje, A Anderson, A Lima, M Obideen, D Haussen, R Dharia, M Frankel, V Patel, K Owada, A Saad, L Amerson, C Horn, S Doppelheuer, K Schindler, DK Lopes, M Chen, R Moftakhar, C Anton, M Smreczak, JS Carpenter, S Boo, A Rai, T Roberts, A Tarabishy, L Gutmann, C Brooks, J Brick, J Domico, G Reimann, K Hinrichs, M Becker, E Heiss, C Selle, A Witteler, S Al-Boutros, M-J Danch, A Ranft, S Rohde, K Burg, C Weimar, V Zegarac, C Hartmann, M Schlamann, S Göricke, A Ringlestein, I 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Henon, Erwah Kalsoum, Christian Lucas, Jean-Pierre Pruvo, Paolo Zuniga, Caroline Arquizan, Vincent Costalat, Paolo Machi, Isabelle Mourand, Carlos Riquelme, Pierre Bounolleau, Charles Arteaga, Anthony Faivre, Marc Bintner, Patrice Tournebize, Cyril Charlin, Françoise Darcel, Pascale Gauthier-Lasalarie, Marcia Jeremenko, Servane Mouton, Jean-Baptiste Zerlauth, Chantal Lamy, Deramond Hervé, Hosseini Hassan, André Gaston, Francis-Guy Barral, Pierre Garnier, Rémy Beaujeux, Valérie Wolff, Denis Herbreteau, Séverine Debiais, Alicia Murray, Gary Ford, Andy Clifton, Janet Freeman, Ian Ford, Hugh Markus, Joanna Wardlaw, Andy Molyneux, Thompson Robinson, Steff Lewis, John Norrie, Fergus Robertson, Richard Perry, Anand Dixit, Andrew Clifton, Christine Roffe, Sanjeev Nayak, Kyriakos Lobotesis, Craig Smith, Amit Herwadkar, Naga Kandasamy, Tony Goddard, John Bamford, Ganesh Subramanian, Rob Lenthall, Edward Littleton, Sal Lamin, Kelley Storey, Rita Ghatala, Azra Banaras, John Aeron-Thomas, Bath Hazel, Holly Maguire, Emelda Veraque, Louise Harrison, Rekha Keshvara, James Cunningham, Clinical Neurophysiology, Weimar, Christian (Beitragende*r), Radiology and nuclear medicine, Rheumatology, ACS - Atherosclerosis & ischemic syndromes, RS: Carim - B05 Cerebral small vessel disease, RS: CARIM - R3.03 - Cerebral small vessel disease, RS: Carim - B06 Imaging, Beeldvorming, MUMC+: DA BV Medisch Specialisten Radiologie (9), RS: CARIM - R3.11 - Imaging, MUMC+: MA Neurologie (3), Klinische Neurowetenschappen, MUMC+: MA AIOS Neurologie (9), The Royal Melbourne Hospital, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Stanford University, University of Calgary, The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University [Maastricht], Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute of Neuroscience [Newcastle] (ION), Newcastle University [Newcastle], Universitat Autònoma de Barcelona (UAB), Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Alberta, Centre d'Investigation Clinique - Innovation Technologique [Nancy] (CIC-IT), Monash University [Melbourne], St George’s University Hospitals, Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Dalhousie University [Halifax], Neuroradiologie [Hôpital Gui de Chauliac], Hôpital Gui de Chauliac [Montpellier], Service de Neuroradiologie [Rennes], CHU Pontchaillou [Rennes], St. Michael's Hospital, University of California [Los Angeles] (UCLA), University of California, University Medical Center of Schleswig–Holstein = Universitätsklinikum Schleswig-Holstein (UKSH), Kiel University, Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), University at Buffalo [SUNY] (SUNY Buffalo), State University of New York (SUNY), Toronto Western Hospital, Hôpital Foch [Suresnes], Vall d'Hebron University Hospital [Barcelona], Département de neuroradiologie diagnostique et thérapeutique [CHRU Nancy], Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), University of Glasgow, Queen Elizabeth University Hospital (Glasgow), David Geffen School of Medicine [Los Angeles], University of California-University of California, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Radiology & Nuclear Medicine, Public Health, Neurology, Radiology and Nuclear Medicine, ACS - Microcirculation, ANS - Neurovascular Disorders, ACS - Amsterdam Cardiovascular Sciences, Graduate School, ACS - Pulmonary hypertension & thrombosis, AGEM - Digestive immunity, AGEM - Re-generation and cancer of the digestive system, ARD - Amsterdam Reproduction and Development, Biomedical Engineering and Physics, APH - Personalized Medicine, APH - Quality of Care, and AMS - Restoration & Development
Subjects: SELECTION, COMPUTED TOMOGRAPHIC PERFUSION, Medizin, Perfusion scanning, 030204 cardiovascular system & hematology, Brain Ischemia, 0302 clinical medicine, Modified Rankin Scale, REPERFUSION, Stroke, ComputingMilieux_MISCELLANEOUS, Thrombectomy, Aged, 80 and over, medicine.diagnostic_test, Penumbra, Endovascular Procedures, Brain, Middle Aged, Magnetic Resonance Imaging, 3. Good health, Treatment Outcome, Cerebral blood flow, Tissue Plasminogen Activator, INFARCT, Cardiology, Female, TRIAL, CT, medicine.medical_specialty, Perfusion Imaging, Neuroimaging, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 03 medical and health sciences, Fibrinolytic Agents, ALTEPLASE, Internal medicine, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, Aged, business.industry, MECHANICAL THROMBECTOMY, Other Research Radboud Institute for Health Sciences [Radboudumc 0], Magnetic resonance imaging, Odds ratio, medicine.disease, Neurology (clinical), business, Tomography, X-Ray Computed, 030217 neurology & neurosurgery, Fibrinolytic agent, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background CT perfusion (CTP) and diffusion or perfusion MRI might assist patient selection for endovascular thrombectomy. We aimed to establish whether imaging assessments of irreversibly injured ischaemic core and potentially salvageable penumbra volumes were associated with functional outcome and whether they interacted with the treatment effect of endovascular thrombectomy on functional outcome.Methods In this systematic review and meta-analysis, the HERMES collaboration pooled patient-level data from all randomised controlled trials that compared endovascular thrombectomy (predominantly using stent retrievers) with standard medical therapy in patients with anterior circulation ischaemic stroke, published in PubMed from Jan 1,2010, to May 31, 2017. The primary endpoint was functional outcome, assessed by the modified Rankin Scale (mRS) at 90 days after stroke. Ischaemic core was estimated, before treatment with either endovascular thrombectomy or standard medical therapy, by CTP as relative cerebral blood flow less than 30% of normal brain blood flow or by MRI as an apparent diffusion coefficient less than 620 mu m(2)/s. Critically hypoperfused tissue was estimated as the volume of tissue with a CTP time to maximum longer than 6 s. Mismatch volume (ie, the estimated penumbral volume) was calculated as critically hypoperfused tissue volume minus ischaemic core volume. The association of ischaemic core and penumbral volumes with 90-day mRS score was analysed with multivariable logistic regression (functional independence, defined as mRS score 0-2) and ordinal logistic regression (functional improvement by at least one mRS category) in all patients and in a subset of those with more than 50% endovascular reperfusion, adjusted for baseline prognostic variables. The meta-analysis was prospectively designed by the HERMES executive committee, but not registered.Findings We identified seven studies with 1764 patients, all of which were included in the meta-analysis. CTP was available and assessable for 591 (34%) patients and diffusion MRI for 309 (18%) patients. Functional independence was worse in patients who had CTP versus those who had diffusion MRI, after adjustment for ischaemic core volume (odds ratio [OR] 0.47 [95% CI 0.30-0.72], p=0.0007), so the imaging modalities were not pooled. Increasing ischaemic core volume was associated with reduced likelihood of functional independence (CTP OR 0.77 [0.69-0.86] per 10 mL, p(interaction)=0.29; diffusion MRI OR 0.87 [0.81-0.94] per 10 mL, p(interaction)=0.94). Mismatch volume, examined only in the CTP group because of the small numbers of patients who had perfusion MRI, was not associated with either functional independence or functional improvement. In patients with CTP with more than 50% endovascular reperfusion (n=186), age, ischaemic core volume, and imaging-to-reperfusion time were independently associated with functional improvement. Risk of bias between studies was generally low.Interpretation Estimated ischaemic core volume was independently associated with functional independence and functional improvement but did not modify the treatment benefit of endovascular thrombectomy over standard medical therapy for improved functional outcome. Combining ischaemic core volume with age and expected imagingto-reperfusion time will improve assessment of prognosis and might inform endovascular thrombectomy treatment decisions. Copyright (C) 2018 Elsevier Ltd. All rights reserved.
Published: 2019
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50. Development and Validation of a Prognostic Model of Swallowing Recovery and Enteral Tube Feeding After Ischemic Stroke

Author: Florian Brugger, Werner Krammer, Anna Müller, Barbara Tettenborn, Concetta Manno, Marcel Arnold, Marian Galovic, Jochen Rosenfeld, Simon Jung, Maren Leifke, Anne Julia Stauber, Petra Saladin, Georg Kägi, Thorsten Niemann, Philippe Lyrer, Hakan Sarikaya, Josemir W. Sander, Natascha Leisi, Timo Kahles, Alexandros A Polymeris, Urs Fischer, Philipp Balcerak, Carlo W. Cereda, Jochen Vehoff, Sandro J. Stoeckli, Sebastian Thilemann, Bruno Weder, Krassen Nedeltchev, M. Müller, and Gian Marco De Marchis
Subjects: Male, medicine.medical_specialty, Time Factors, medicine.medical_treatment, Clinical prediction rule, Brain Ischemia, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Enteral Nutrition, Swallowing, Interquartile range, Internal medicine, Percutaneous endoscopic gastrostomy, medicine, Humans, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, 610 Medicine & health, Stroke, Intubation, Gastrointestinal, Original Investigation, Aged, Aged, 80 and over, Gastrostomy, business.industry, Recovery of Function, Middle Aged, medicine.disease, Prognosis, Dysphagia, Mobile Applications, Deglutition, Female, Neurology (clinical), medicine.symptom, business, Deglutition Disorders, 030217 neurology & neurosurgery, Switzerland, Cohort study
Abstract: IMPORTANCE: Predicting the duration of poststroke dysphagia is important to guide therapeutic decisions. Guidelines recommend nasogastric tube (NGT) feeding if swallowing impairment persists for 7 days or longer and percutaneous endoscopic gastrostomy (PEG) placement if dysphagia does not recover within 30 days, but, to our knowledge, a systematic prediction method does not exist. OBJECTIVE: To develop and validate a prognostic model predicting swallowing recovery and the need for enteral tube feeding. DESIGN, SETTING, AND PARTICIPANTS: We enrolled participants with consecutive admissions for acute ischemic stroke and initially severe dysphagia in a prospective single-center derivation (2011-2014) and a multicenter validation (July 2015-March 2018) cohort study in 5 tertiary stroke referral centers in Switzerland. EXPOSURES: Severely impaired oral intake at admission (Functional Oral Intake Scale score
Published: 2019
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