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1. Post-acute COVID-19 outcomes including participant-reported long COVID: amubarvimab/romlusevimab versus placebo in the ACTIV-2 trialResearch in context

Author

Teresa H. Evering, Carlee Moser, Nikolaus Jilg, Justin Ritz, David A. Wohl, Jonathan Z. Li, David Margolis, Arzhang Cyrus Javan, Joseph J. Eron, Judith S. Currier, Eric S. Daar, Davey M. Smith, Michael D. Hughes, Kara W. Chew, Kara Chew, David (Davey) Smith, Eric Daar, David Wohl, Judith Currier, Joseph Eron, Michael Hughes, Mark Giganti, Lara Hosey, Jhoanna Roa, Nilam Patel, Kelly Colsh, Irene Rwakazina, Justine Beck, Scott Sieg, Jonathan Li, Courtney Fletcher, William Fischer, Rachel Bender Ignacio, Sandra Cardoso, Katya Corado, Prasanna Jagannathan, Alan Perelson, Sandy Pillay, Cynthia Riviere, Upinder Singh, Babafemi Taiwo, Joan Gottesman, Matthew Newell, Susan Pedersen, Joan Dragavon, Cheryl Jennings, Brian Greenfelder, William Murtaugh, Jan Kosmyna, Morgan Gapara, Akbar Shahkolahi, Verónica Lacal, Diego Salusso, Sebastian Nuñez, Marcelo Rodrigo Rodriguez, Luciana Laborde, Marcelo Papasidero, Luis Wehbe, Mariana Gonzalez, Felicitas Fernandez Voena, Tomas Alvarez, Amaru Lopez, Virginia Huhn, Ulises D'Andrea Nores, Pablo Dieser, Fernando Bordese, Marisa Mussi, Rodrigo de Carvalho Santana, Adriana Aparecida Tiraboschi Bárbaro, Breno Santos, Rita de Cássia Alves Lira, Andre Luiz Machado da Silva, Sandra Wagner Cardoso, Maria Pia Diniz Ribeiro, Nathália Soliva, Eduardo Vasconcellos, Jorge Eurico Ribeiro, Miriam Amaral Enéas, Jorge Pinto, Julia Fonseca de Morais Caporali, Flávia Gomes Faleiro Ferreira, Norma Erendira Rivera Martinez, Victor Casildo Bohorquez Lopez, Melchor Victor Frias, Krystle Fetalvero, Alyxzza Maranan, Jennifer Rosa, Thomas Coetzer, Maureen Mohata, Sr., Umesh Lalloo, Penelope Madlala, Larisha Pillay-Ramaya, Jaclyn Ann Bennet, Noluthando Mwelase, Nokuphiwa Mbhele, Frederick Petrick, Leonard Joubert, Rose Mbali, Sr., Natasha Joseph, Mmatsie Manentsa, Eugene van der Walt, Mduduzi Sandile Lawrance Masilela, Zinhle Zwane, Tendai Chiperera, Lerato Mohapi, Suri Moonsamy, Usha Singh, Kirsten McHarry, Elizma Snyman, Pieter Lennox, James Craig Innes, Oteng Letlape, Olebogeng Jonkane, William Brumskine, Tania Adonis, Ni Ni Sein, Modulakgotla Sebe, Yacoob Vahed, Nazreen Jeewa Hussen, Ismail Mitha, Vasundhara Cheekati, Purna Cheekati, Christie Lummus, Samuel Idarraga, Andrew Kim, David N. Pham, Wei-Hsin Kao, Michael M. Pfeffer, Miriam Batule Dominguez, Anju Malik, Anna Bryan, Melanie Arnold, Idania Fernandez, Cinzia Karpf, Aniuska Ruiz, David Taylor, Eric Folkens, Jennifer Manne, Sigal Yawetz, Cheryl Keenan, Emeka Eziri, Carl Fichtenbaum, Jenifer Baer, Sarah Trentman, Robert Call, Leroy Vaughan, Aaron Milstone, Jamie Alex Slandzicki, Jessica Wallan, Clinton Guillory, Nancy Andrews, Leslie Hughes, Jonathan Berardi, Celine Arar, Randall Quinn, Jorge P. Amaya, Marissa Gomez-Martinez, Luis Cantu, Monica Betancourt-Garcia, Nwora Lance Okeke, Charles M. Burns, Fadi Haddad, Victoria Haddad, Augusto Focil, Griselda Rosas, Susana Moyano, Yaneicy Gonzalez Rojas, Ahmad Aswad, Yevgeniy Bukhman, Manish Jain, Eugene Bukhman, Humam Farah, Rebekah McClain, Sadia Shaik, Timothy Hatlen, Deepa Gotur, Joseph Surber, Jeffrey Kingsley, April Pixler, Alex Zopo, Jack Herman, Craig Herman, Ramon Leon, Boris Nikolov, Fernando Gonzalez Vergara, Ana I. Gonzalez, Noemi Gonzalez, Michael Gelman, Olga Andriunas, Zarema Jagizarov, Jan Westerman, David Davis, Donna Sherer, Kelly Dooley, Becky Becker, Adaliah Wilkins, Jose Pérez, Eloy Roman, Heriberto Fernández, Bharat Mocherla, Kelly Beck, Valarie Maldonado, Jennifer Veltman, Rajesh Gandhi, Katrina Shea, Matthew Planchon, Laura Bogan Herpel, Kaushlendra K. Tripathi, Donald C. Day, John Pullman, Sr., Erin Williams-Leber, Misty Johnson, Michelle Hecker, Ann Avery, Keila Hoover, George W. Monlux, Elizabeth Juneja, Jr., Arthur Wernick, Karelia Ruiz, Maureen Hernández, Yadilys Pérez, Babafemi O. Taiwo, Claudia Hawkins, Baiba Berzins, Carlos Malvestutto, Heather Harber, Robyn Cicarella, Edwin DeJesus, Charlotte-Paige Rolle, Almena L. Free, Sallie D. Pulliam, Debra Weinstein, Rosa M. Suarez, Ezequiel Socorro, Estefania Socorro, Gene Neytman, Raymond Easley, Mariam Aziz, Joan Swiatek, Avish Nagpal, Breanna Kompelien, Kathryn McEvoy, Susan E. Hoover, Allison Lutz, Jessica Just, Manuel Hernandez, Yanly B. Victoria, Gabriel Rodriguez, Divya Pathak, Joshua J. Ordway, Megan Heffner, Patrick Weston, Khalilah Weston, Madhu Choudhary, Jennifer Sullivano, Olayemi Osiyemi, Myriam Izquierdo, Odelsey Torna, Brian Clemency, Renoj Varughese, Joshua Lynch, Aleen Khodabakhshian, Samantha Fortier, Christopher Coyne, Alexandrea Cronin, Constance Benson, Steven Hendrickx, Rosemarie Ramirez, Anne Luetkemeyer, Suzanne Hendler, Dennis Dentoni-Lasofsky, Mobeen Rathore, Saniyyah Mahmoudi, Amna Riaz, Mario Castro, Leslie Spikes, Chase Hall, Jonathan Oakes, Amy James Loftis, Pablo Tebas, William Short, Michael P. Dube, Saahir Khan, Luis M. Mendez, Sarah McGuffin, Chris Jonsson, Mamta K. Jain, Smruthi Senthil, Kimberly Turner-Gray, Sanjay Mehta, Mary Lewinski, Masoud Azizad, Christopher Chow, Lisa Nakatani, Derrick Williamson, Hisham Atriss, Matthew Caloura, Midhun Malla, Hannah Hazard-Jenkins, Aimee Wilkin, Jamraus Fayssoux, Hannah Seagle, Rachel Presti, and Alem Haile

Subjects
COVID-19, Monoclonal antibodies, Outpatient treatment, Clinical trial, Post COVID conditions, Long COVID, Medicine (General), R5-920
Abstract

Summary: Background: It is unknown if early COVID-19 monoclonal antibody (mAb) therapy can reduce risk of Long COVID. The mAbs amubarvimab/romlusevimab were previously demonstrated to reduce risk of hospitalization/death by 79%. This study assessed the impact of amubarvimab/romlusevimab on late outcomes, including Long COVID. Methods: Non-hospitalized high-risk adults within 10 days of COVID-19 symptom onset enrolled in a randomized, double-blind, placebo-controlled phase 2/3 trial of amubarvimab/romlusevimab for COVID-19 treatment. Late symptoms, assessed using a participant-completed symptom diary, were a pre-specified exploratory endpoint. The primary outcome for this analysis was the composite of Long COVID by participant self-report (presence of COVID-19 symptoms as recorded in the diary at week 36) or hospitalization or death by week 36. Inverse probability weighting (IPW) was used to address incomplete outcome ascertainment, giving weighted risk ratios (wRR) comparing amubarvimab/romlusevimab to placebo. Findings: Participants received amubarvimab/romlusevimab (n = 390) or placebo (n = 390) between January and July 2021. Median age was 49 years, 52% were female, 18% Black/African American, 49% Hispanic/Latino, and 9% COVID-19-vaccinated at entry. At week 36, 103 (13%) had incomplete outcome ascertainment, and 66 (17%) on amubarvimab/romlusevimab and 92 (24%) on placebo met the primary outcome (wRR = 0.70, 95% confidence interval (CI) 0.53–0.93). The difference was driven by fewer hospitalizations/deaths with amubarvimab/romlusevimab (4%) than placebo (13%). Among 652 participants with available diary responses, 53 (16%) on amubarvimab/romlusevimab and 44 (14%) on placebo reported presence of Long COVID. Interpretation: Amubarvimab/romlusevimab treatment, while highly effective in preventing hospitalizations/deaths, did not reduce risk of Long COVID. Additional interventions are needed to prevent Long COVID. Funding: National Institute of Allergy and Infectious Diseases of the National Institutes of Health. Amubarvimab and romlusevimab supplied by Brii Biosciences.

Published
2024
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2. Anticoagulant selection in relation to the SAMe-TT2R2 score in patients with atrial fibrillation: The GLORIA-AF registry

Author

George Ntaios, Menno V. Huisman, Hans-Christoph Diener, Jonathan L. Halperin, Christine Teutsch, Sabrina Marler, Venkatesh K. Gurusamy, Milla Thompson, Gregory Y.H. Lip, Brian Olshansky, Dzifa Wosornu Abban, Nasser Abdul, Atilio Marcelo Abud, Fran Adams, Srinivas Addala, Pedro Adragão, Walter Ageno, Rajesh Aggarwal, Sergio Agosti, Piergiuseppe Agostoni, Francisco Aguilar, Julio Aguilar Linares, Luis Aguinaga, Jameel Ahmed, Allessandro Aiello, Paul Ainsworth, Jorge Roberto Aiub, Raed Al-Dallow, Lisa Alderson, Jorge Antonio Aldrete Velasco, Dimitrios Alexopoulos, Fernando Alfonso Manterola, Pareed Aliyar, David Alonso, Fernando Augusto Alves da Costa, José Amado, Walid Amara, Mathieu Amelot, Nima Amjadi, Fabrizio Ammirati, Marianna Andrade, Nabil Andrawis, Giorgio Annoni, Gerardo Ansalone, M.Kevin Ariani, Juan Carlos Arias, Sébastien Armero, Chander Arora, Muhammad Shakil Aslam, M. Asselman, Philippe Audouin, Charles Augenbraun, S. Aydin, Ivaneta Ayryanova, Emad Aziz, Luciano Marcelo Backes, E. Badings, Ermentina Bagni, Seth H. Baker, Richard Bala, Antonio Baldi, Shigenobu Bando, Subhash Banerjee, Alan Bank, Gonzalo Barón Esquivias, Craig Barr, Maria Bartlett, Vanja Basic Kes, Giovanni Baula, Steffen Behrens, Alan Bell, Raffaella Benedetti, Juan Benezet Mazuecos, Bouziane Benhalima, Jutta Bergler-Klein, Jean-Baptiste Berneau, Richard A. Bernstein, Percy Berrospi, Sergio Berti, Andrea Berz, Elizabeth Best, Paulo Bettencourt, Robert Betzu, Ravi Bhagwat, Luna Bhatta, Francesco Biscione, Giovanni BISIGNANI, Toby Black, Michael J. Bloch, Stephen Bloom, Edwin Blumberg, Mario Bo, Ellen Bøhmer, Andreas Bollmann, Maria Grazia Bongiorni, Giuseppe Boriani, D.J. Boswijk, Jochen Bott, Edo Bottacchi, Marica Bracic Kalan, Drew Bradman, Donald Brautigam, Nicolas Breton, P.J.A.M. Brouwers, Kevin Browne, Jordi Bruguera Cortada, A. Bruni, Claude Brunschwig, Hervé Buathier, Aurélie Buhl, John Bullinga, Jose Walter Cabrera, Alberto Caccavo, Shanglang Cai, Sarah Caine, Leonardo Calò, Valeria Calvi, Mauricio Camarillo Sánchez, Rui Candeias, Vincenzo Capuano, Alessandro Capucci, Ronald Caputo, Tatiana Cárdenas Rizo, Francisco Cardona, Francisco Carlos da Costa Darrieux, Yan Carlos Duarte Vera, Antonio Carolei, Susana Carreño, Paula Carvalho, Susanna Cary, Gavino Casu, Claudio Cavallini, Guillaume Cayla, Aldo Celentano, Tae-Joon Cha, Kwang Soo Cha, Jei Keon Chae, Kathrine Chalamidas, Krishnan Challappa, Sunil Prakash Chand, Harinath Chandrashekar, Ludovic Chartier, Kausik Chatterjee, Carlos Antero Chavez Ayala, Aamir Cheema, Amjad Cheema, Lin Chen, Shih-Ann Chen, Jyh Hong Chen, Fu-Tien Chiang, Francesco Chiarella, Lin Chih-Chan, Yong Keun Cho, Jong-Il Choi, Dong Ju Choi, Guy Chouinard, Danny Hoi-Fan Chow, Dimitrios Chrysos, Galina Chumakova, Eduardo Julián José Roberto Chuquiure Valenzuela, Nicoleta Cindea Nica, David J. Cislowski, Anthony Clay, Piers Clifford, Andrew Cohen, Michael Cohen, Serge Cohen, Furio Colivicchi, Ronan Collins, Paolo Colonna, Steve Compton, Derek Connolly, Alberto Conti, Gabriel Contreras Buenostro, Gregg Coodley, Martin Cooper, Julian Coronel, Giovanni Corso, Juan Cosín Sales, Yves Cottin, John Covalesky, Aurel Cracan, Filippo Crea, Peter Crean, James Crenshaw, Tina Cullen, Harald Darius, Patrick Dary, Olivier Dascotte, Ira Dauber, Vicente Davalos, Ruth Davies, Gershan Davis, Jean-Marc Davy, Mark Dayer, Marzia De Biasio, Silvana De Bonis, Raffaele De Caterina, Teresiano De Franceschi, J.R. de Groot, José De Horta, Axel De La Briolle, Gilberto de la Pena Topete, Angelo Amato Vicenzo de Paola, Weimar de Souza, A. de Veer, Luc De Wolf, Eric Decoulx, Sasalu Deepak, Pascal Defaye, Freddy Del-Carpio Munoz, Diana Delic Brkljacic, N. Joseph Deumite, Silvia Di Legge, Igor Diemberger, Denise Dietz, Pedro Dionísio, Qiang Dong, Fabio Rossi dos Santos, Elena Dotcheva, Rami Doukky, Anthony D'Souza, Simon Dubrey, Xavier Ducrocq, Dmitry Dupljakov, Mauricio Duque, Dipankar Dutta, Nathalie Duvilla, A. Duygun, Rainer Dziewas, Charles B. Eaton, William Eaves, L.A. Ebels-Tuinbeek, Clifford Ehrlich, Sabine Eichinger-Hasenauer, Steven J. Eisenberg, Adnan El Jabali, Mahfouz El Shahawy, Mauro Esteves Hernandes, Ana Etxeberria Izal, Rudolph Evonich, III, Oksana Evseeva, Andrey Ezhov, Raed Fahmy, Quan Fang, Ramin Farsad, Laurent Fauchier, Stefano Favale, Maxime Fayard, Jose Luis Fedele, Francesco Fedele, Olga Fedorishina, Steven R. Fera, Luis Gustavo Gomes Ferreira, Jorge Ferreira, Claudio Ferri, Anna Ferrier, Hugo Ferro, Alexandra Finsen, Brian First, Stuart Fischer, Catarina Fonseca, Luísa Fonseca Almeida, Steven Forman, Brad Frandsen, William French, Keith Friedman, Athena Friese, Ana Gabriela Fruntelata, Shigeru Fujii, Stefano Fumagalli, Marta Fundamenski, Yutaka Furukawa, Matthias Gabelmann, Nashwa Gabra, Niels Gadsbøll, Michel Galinier, Anders Gammelgaard, Priya Ganeshkumar, Christopher Gans, Antonio Garcia Quintana, Olivier Gartenlaub, Achille Gaspardone, Conrad Genz, Frédéric Georger, Jean-Louis Georges, Steven Georgeson, Evaldas Giedrimas, Mariusz Gierba, Ignacio Gil Ortega, Eve Gillespie, Alberto Giniger, Michael C. Giudici, Alexandros Gkotsis, Taya V. Glotzer, Joachim Gmehling, Jacek Gniot, Peter Goethals, Seth Goldbarg, Ronald Goldberg, Britta Goldmann, Sergey Golitsyn, Silvia Gómez, Juan Gomez Mesa, Vicente Bertomeu Gonzalez, Jesus Antonio Gonzalez Hermosillo, Víctor Manuel González López, Hervé Gorka, Charles Gornick, Diana Gorog, Venkat Gottipaty, Pascal Goube, Ioannis Goudevenos, Brett Graham, G. Stephen Greer, Uwe Gremmler, Paul G. Grena, Martin Grond, Edoardo Gronda, Gerian Grönefeld, Xiang Gu, Ivett Guadalupe Torres Torres, Gabriele Guardigli, Carolina Guevara, Alexandre Guignier, Michele Gulizia, Michael Gumbley, Albrecht Günther, Andrew Ha, Georgios Hahalis, Joseph Hakas, Christian Hall, Bing Han, Seongwook Han, Joe Hargrove, David Hargroves, Kenneth B. Harris, Tetsuya Haruna, Emil Hayek, Jeff Healey, Steven Hearne, Michael Heffernan, Geir Heggelund, J.A. Heijmeriks, Maarten Hemels, I. Hendriks, Sam Henein, Sung-Ho Her, Paul Hermany, Jorge Eduardo Hernández Del Río, Yorihiko Higashino, Michael Hill, Tetsuo Hisadome, Eiji Hishida, Etienne Hoffer, Matthew Hoghton, Kui Hong, Suk keun Hong, Stevie Horbach, Masataka Horiuchi, Yinglong Hou, Jeff Hsing, Chi-Hung Huang, David Huckins, kathy Hughes, A. Huizinga, E.L. Hulsman, Kuo-Chun Hung, Gyo-Seung Hwang, Margaret Ikpoh, Davide Imberti, Hüseyin Ince, Ciro Indolfi, Shujiro Inoue, Didier Irles, Harukazu Iseki, C. Noah Israel, Bruce Iteld, Venkat Iyer, Ewart Jackson-Voyzey, Naseem Jaffrani, Frank Jäger, Martin James, Sung-Won Jang, Nicolas Jaramillo, Nabil Jarmukli, Robert J. Jeanfreau, Ronald D. Jenkins, Carlos Jerjes Sánchez, Javier Jimenez, Robert Jobe, Tomas Joen-Jakobsen, Nicholas Jones, Jose Carlos Moura Jorge, Bernard Jouve, Byung Chun Jung, Kyung Tae Jung, Werner Jung, Mikhail Kachkovskiy, Krystallenia Kafkala, Larisa Kalinina, Bernd Kallmünzer, Farzan Kamali, Takehiro Kamo, Priit Kampus, Hisham Kashou, Andreas Kastrup, Apostolos Katsivas, Elizabeth Kaufman, Kazuya Kawai, Kenji Kawajiri, John F. Kazmierski, P. Keeling, José Francisco Kerr Saraiva, Galina Ketova, AJIT Singh Khaira, Aleksey Khripun, Doo-Il Kim, Young Hoon Kim, Nam Ho Kim, Dae Kyeong Kim, Jeong Su Kim, June Soo Kim, Ki Seok Kim, Jin bae Kim, Elena Kinova, Alexander Klein, James J. Kmetzo, G. Larsen Kneller, Aleksandar Knezevic, Su Mei Angela Koh, Shunichi Koide, Anastasios Kollias, J.A. Kooistra, Jay Koons, Martin Koschutnik, William J. Kostis, Dragan Kovacic, Jacek Kowalczyk, Natalya Koziolova, Peter Kraft, Johannes A. Kragten, Mori Krantz, Lars Krause, B.J. Krenning, F. Krikke, Z. Kromhout, Waldemar Krysiak, Priya Kumar, Thomas Kümler, Malte Kuniss, Jen-Yuan Kuo, Achim Küppers, Karla Kurrelmeyer, Choong Hwan Kwak, Bénédicte Laboulle, Arthur Labovitz, Wen Ter Lai, Andy Lam, Yat Yin Lam, Fernando Lanas Zanetti, Charles Landau, Giancarlo Landini, Estêvão Lanna Figueiredo, Torben Larsen, Karine Lavandier, Jessica LeBlanc, Moon Hyoung Lee, Chang-Hoon Lee, John Lehman, Ana Leitão, Nicolas Lellouche, Malgorzata Lelonek, Radoslaw Lenarczyk, T. Lenderink, Salvador León González, Peter Leong-Sit, Matthias Leschke, Nicolas Ley, Zhanquan Li, Xiaodong Li, Weihua Li, Xiaoming Li, Christhoh Lichy, Ira Lieber, Ramon Horacio Limon Rodriguez, Hailong Lin, Feng Liu, Hengliang Liu, Guillermo Llamas Esperon, Nassip Llerena Navarro, Eric Lo, Sergiy Lokshyn, Amador López, José Luís López-Sendón, Adalberto Menezes Lorga Filho, Richard S. Lorraine, Carlos Alberto Luengas, Robert Luke, Ming Luo, Steven Lupovitch, Philippe Lyrer, Changsheng Ma, Genshan Ma, Irene Madariaga, Koji Maeno, Dominique Magnin, Gustavo Maid, Sumeet K. Mainigi, Konstantinos Makaritsis, Rohit Malhotra, Rickey Manning, Athanasios Manolis, Helard Andres Manrique Hurtado, Ioannis Mantas, Fernando Manzur Jattin, Vicky Maqueda, Niccolo Marchionni, Francisco Marin Ortuno, Antonio Martín Santana, Jorge Martinez, Petra Maskova, Norberto Matadamas Hernandez, Katsuhiro Matsuda, Tillmann Maurer, Ciro Mauro, Erik May, Nolan Mayer, John McClure, Terry McCormack, William McGarity, Hugh McIntyre, Brent McLaurin, Feliz Alvaro Medina Palomino, Francesco Melandri, Hiroshi Meno, Dhananjai Menzies, Marco Mercader, Christian Meyer, Beat j. Meyer, Jacek Miarka, Frank Mibach, Dominik Michalski, Patrik Michel, Rami Mihail Chreih, Ghiath Mikdadi, Milan Mikus, Davor Milicic, Constantin Militaru, Sedi Minaie, Bogdan Minescu, Iveta Mintale, Tristan Mirault, Michael J. Mirro, Dinesh Mistry, Nicoleta Violeta Miu, Naomasa Miyamoto, Tiziano Moccetti, Akber Mohammed, Azlisham Mohd Nor, Michael Mollerus, Giulio Molon, Sergio Mondillo, Patrícia Moniz, Lluis Mont, Vicente Montagud, Oscar Montaña, Cristina Monti, Luciano Moretti, Kiyoo Mori, Andrew Moriarty, Jacek Morka, Luigi Moschini, Nikitas Moschos, Andreas Mügge, Thomas J. Mulhearn, Carmen Muresan, Michela Muriago, Wlodzimierz Musial, Carl W. Musser, Francesco Musumeci, Thuraia Nageh, Hidemitsu Nakagawa, Yuichiro Nakamura, Toru Nakayama, Gi-Byoung Nam, Michele Nanna, Indira Natarajan, Hemal M. Nayak, Stefan Naydenov, Jurica Nazli, Alexandru Cristian Nechita, Libor Nechvatal, Sandra Adela Negron, James Neiman, Fernando Carvalho Neuenschwander, David Neves, Anna Neykova, Ricardo Nicolás Miguel, George Nijmeh, Alexey Nizov, Rodrigo Noronha Campos, Janko Nossan, Tatiana Novikova, Ewa Nowalany-Kozielska, Emmanuel Nsah, Juan Carlos Nunez Fragoso, Svetlana Nurgalieva, Dieter Nuyens, Ole Nyvad, Manuel Odin de Los Rios Ibarra, Philip O'Donnell, Martin O'Donnell, Seil Oh, Yong Seog Oh, Dongjin Oh, Gilles O'Hara, Kostas Oikonomou, Claudia Olivares, Richard Oliver, Rafael Olvera Ruiz, Christoforos Olympios, Anna omaszuk-Kazberuk, Joaquín Osca Asensi, eena Padayattil jose, Francisco Gerardo Padilla Padilla, Victoria Padilla Rios, Giuseppe Pajes, A. Shekhar Pandey, Gaetano Paparella, F. Paris, Hyung Wook Park, Jong Sung Park, Fragkiskos Parthenakis, Enrico Passamonti, Rajesh J. Patel, Jaydutt Patel, Mehool Patel, Janice Patrick, Ricardo Pavón Jimenez, Analía Paz, Vittorio Pengo, William Pentz, Beatriz Pérez, Alma Minerva Pérez Ríos, Alejandro Pérez-Cabezas, Richard Perlman, Viktor Persic, Francesco Perticone, Terri K. Peters, Sanjiv Petkar, Luis Felipe Pezo, Christian Pflücke, David N. Pham, Roland T. Phillips, Stephen Phlaum, Denis Pieters, Julien Pineau, Arnold Pinter, Fausto Pinto, R. Pisters, Nediljko Pivac, Darko Pocanic, Cristian Podoleanu, Alessandro Politano, Zdravka Poljakovic, Stewart Pollock, Jose Polo Garcéa, Holger Poppert, Maurizio Porcu, Antonio Pose Reino, Neeraj Prasad, Dalton Bertolim Précoma, Alessandro Prelle, John Prodafikas, Konstantin Protasov, Maurice Pye, Zhaohui Qiu, Jean-Michel Quedillac, Dimitar Raev, Carlos Antonio Raffo Grado, Sidiqullah Rahimi, Arturo Raisaro, Bhola Rama, Ricardo Ramos, Maria Ranieri, Nuno Raposo, Eric Rashba, Ursula Rauch-Kroehnert, Ramakota Reddy, Giulia Renda, Shabbir Reza, Luigi Ria, Dimitrios Richter, Hans Rickli, Werner Rieker, Tomas Ripolil Vera, Luiz Eduardo Ritt, Douglas Roberts, Ignacio Rodriguez Briones, Aldo Edwin Rodriguez Escudero, Carlos Rodríguez Pascual, Mark Roman, Francesco Romeo, E. Ronner, Jean-Francois Roux, Nadezda Rozkova, Miroslav Rubacek, Frank Rubalcava, Andrea M. Russo, Matthieu Pierre Rutgers, Karin Rybak, Samir Said, Tamotsu Sakamoto, Abraham Salacata, Adrien Salem, Rafael Salguero Bodes, Marco A. Saltzman, Alessandro Salvioni, Gregorio Sanchez Vallejo, Marcelo Sanmartín Fernández, Wladmir Faustino Saporito, Kesari Sarikonda, Taishi Sasaoka, Hamdi Sati, Irina Savelieva, Pierre-Jean Scala, Peter Schellinger, Carlos Scherr, Lisa Schmitz, Karl-Heinz Schmitz, Bettina Schmitz, Teresa Schnabel, Steffen Schnupp, Peter Schoeniger, Norbert Schön, Peter Schwimmbeck, Clare Seamark, Greg Searles, Karl-Heinz Seidl, Barry Seidman, Jaroslaw Sek, Lakshmanan Sekaran, Carlo SERRATI, Neerav Shah, Vinay Shah, Anil Shah, Shujahat Shah, Vijay Kumar Sharma, Louise Shaw, Khalid H. Sheikh, Naruhito Shimizu, Hideki Shimomura, Dong-Gu Shin, Eun-Seok Shin, Junya Shite, Gerolamo Sibilio, Frank Silver, Iveta Sime, Tim A. Simmers, Narendra Singh, Peter Siostrzonek, Didier Smadja, David W. Smith, Marcelo Snitman, Dario Sobral Filho, Hassan Soda, Carl Sofley, Adam Sokal, Yannie Soo Oi Yan, Rodolfo Sotolongo, Olga Ferreira de Souza, Jon Arne Sparby, Jindrich Spinar, David Sprigings, Alex C. Spyropoulos, Dimitrios Stakos, Clemens Steinwender, George Stergiou, Ian Stiell, Marcus Stoddard, Anastas Stoikov, Witold Streb, Ioannis Styliadis, Guohai Su, Xi Su, Wanda Sudnik, Kai Sukles, Xiaofei Sun, H. Swart, Janko Szavits-Nossan, Jens Taggeselle, Yuichiro Takagi, Amrit Pal Singh Takhar, Angelika Tamm, Katsumi Tanaka, Tanyanan Tanawuttiwat, Sherman Tang, Aylmer Tang, Giovanni Tarsi, Tiziana Tassinari, Ashis Tayal, Muzahir Tayebjee, J.M. ten Berg, Dan Tesloianu, Salem H.K. The, Dierk Thomas, Serge Timsit, Tetsuya Tobaru, Andrzej R. Tomasik, Mikhail Torosoff, Emmanuel Touze, Elina Trendafilova, W. Kevin Tsai, Hung Fat Tse, Hiroshi Tsutsui, Tian Ming Tu, Ype Tuininga, Minang Turakhia, Samir Turk, Wayne Tcurner, Arnljot Tveit, Richard Tytus, C. Valadão, P.F.M.M. van Bergen, Philippe van de Borne, B.J. van den Berg, C. van der Zwaan, M. Van Eck, Peter Vanacker, Dimo Vasilev, Vasileios Vasilikos, Maxim Vasilyev, Srikar Veerareddy, Mario Vega Miño, Asok Venkataraman, Paolo Verdecchia, Francesco Versaci, Ernst Günter Vester, Hubert Vial, Jason Victory, Alejandro Villamil, Marc Vincent, Anthony Vlastaris, Jürgen vom Dahl, Kishor Vora, Robert B. Vranian, Paul Wakefield, Ningfu Wang, Mingsheng Wang, Xinhua Wang, Feng Wang, Tian Wang, Alberta L. Warner, Kouki Watanabe, Jeanne Wei, Christian Weimar, Stanislav Weiner, Renate Weinrich, Ming-Shien Wen, Marcus Wiemer, Preben Wiggers, Andreas Wilke, David Williams, Marcus L. Williams, Bernhard Witzenbichler, Brian Wong, Ka Sing Lawrence Wong, Beata Wozakowska-Kaplon, Shulin Wu, Richard C. Wu, Silke Wunderlich, Nell Wyatt, John (Jack) Wylie, Yong Xu, Xiangdong Xu, Hiroki Yamanoue, Takeshi Yamashita, Ping Yen Bryan Yan, Tianlun Yang, Jing Yao, Kuo-Ho Yeh, Wei Hsian Yin, Yoto Yotov, Ralf Zahn, Stuart Zarich, Sergei Zenin, Elisabeth Louise Zeuthen, Huanyi Zhang, Donghui Zhang, Xingwei Zhang, Ping Zhang, Jun Zhang, Shui Ping Zhao, Yujie Zhao, Zhichen Zhao, Yang Zheng, Jing Zhou, Sergio Zimmermann, Andrea Zini, Steven Zizzo, Wenxia Zong, and L Steven Zukerman

Subjects
SAMe-TT2R2, atrial fibrillation, non-vitamin-K antagonist oral anticoagulants, vitamin-K-antagonist oral anticoagulants, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Aim: The SAMe-TT2R2 score helps identify patients with atrial fibrillation (AF) likely to have poor anticoagulation control during anticoagulation with vitamin K antagonists (VKA) and those with scores >2 might be better managed with a target-specific oral anticoagulant (NOAC). We hypothesized that in clinical practice, VKAs may be prescribed less frequently to patients with AF and SAMe-TT2R2 scores >2 than to patients with lower scores. Methods and results: We analyzed the Phase III dataset of the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF), a large, global, prospective global registry of patients with newly diagnosed AF and ≥1 stroke risk factor. We compared baseline clinical characteristics and antithrombotic prescriptions to determine the probability of the VKA prescription among anticoagulated patients with the baseline SAMe-TT2R2 score >2 and ≤ 2. Among 17,465 anticoagulated patients with AF, 4,828 (27.6%) patients were prescribed VKA and 12,637 (72.4%) patients an NOAC: 11,884 (68.0%) patients had SAMe-TT2R2 scores 0-2 and 5,581 (32.0%) patients had scores >2. The proportion of patients prescribed VKA was 28.0% among patients with SAMe-TT2R2 scores >2 and 27.5% in those with scores ≤2. Conclusions: The lack of a clear association between the SAMe-TT2R2 score and anticoagulant selection may be attributed to the relative efficacy and safety profiles between NOACs and VKAs as well as to the absence of trial evidence that an SAMe-TT2R2-guided strategy for the selection of the type of anticoagulation in NVAF patients has an impact on clinical outcomes of efficacy and safety. The latter hypothesis is currently being tested in a randomized controlled trial. Clinical trial registration: URL: https://www.clinicaltrials.gov//Unique identifier: NCT01937377, NCT01468701, and NCT01671007.

Published
2021
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3. Spontaneous resolution of atopic dermatitis incidental to participation in benralizumab clinical trial for severe, uncontrolled asthma: a case report

Author

David N. Pham

Subjects
Atopy, Atopic dermatitis, Case report, Benralizumab, Eczema, Asthma, Medicine
Abstract

Abstract Background T cell-mediated eosinophilia is associated with numerous conditions—including atopic dermatitis, food allergies, and asthma—collectively known as the “atopic march.” Benralizumab is a recombinant, humanized, afucosylated monoclonal antibody directed against the ⍺ chain of the eosinophil cell surface receptor IL-5R. Benralizumab treatment causes near-complete depletion of circulating eosinophils and was approved in 2017 for add-on, maintenance treatment of severe asthma with an eosinophilic phenotype, based on the results of the CALIMA and SIROCCO pivotal trials. Benralizumab is not currently approved for the treatment of eosinophilic conditions besides asthma; however, during the CALIMA trial, spontaneous resolution of atopic dermatitis was observed in a patient, concurrent with reduction in her asthma symptoms. Case presentation In January 2015, a 14-year-old Asian girl with severe, uncontrolled asthma was enrolled in CALIMA. The patient’s baseline eosinophil blood count was 1200 cells/μL, her pre-bronchodilator forced expiratory volume in 1 second (FEV1) was 1.9 L and FEV1/forced vital capacity (FVC) ratio was 71.4%, and her post-bronchodilator FEV1 was 3.2 L (FEV1/FVC of 115.9%). Her overall baseline asthma symptom score was 3.9 and her asthma exacerbation rate in the prior year was 4. She also displayed a pronounced, pruritic, chronic, inflammatory rash consistent with atopic dermatitis across her face. The investigator was blinded to the patient’s treatment group during treatment; however, her asthma symptoms diminished over the course of the study (FEV1 at 56 weeks, 3.01 L/110.5% (pre) and 3.25 L/119.3% (post); overall asthma symptom score 2.1; one influenza-associated exacerbation). Furthermore, her atopic dermatitis symptoms resolved spontaneously within the first 5 months of the study. After unblinding, the patient was confirmed to have been randomized to an active treatment arm, and her blood eosinophil count had dropped below the limit of detection after the first study dose. Conclusions Given the potential shared mechanisms between eosinophilic asthma and atopic dermatitis, it is plausible that benralizumab-induced eosinopenia factored into the resolution of the patient’s atopic dermatitis. Further clinical studies are warranted to determine whether benralizumab or other drugs targeted against IL-5/IL-5R may be useful in managing multiple conditions associated with eosinophilia.

Published
2021
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4. Long-term safety and efficacy of tezepelumab in people with severe, uncontrolled asthma (DESTINATION): a randomised, placebo-controlled extension study

Author

Andrew Menzies-Gow, Michael E Wechsler, Christopher E Brightling, Stephanie Korn, Jonathan Corren, Elliot Israel, Geoffrey Chupp, Artur Bednarczyk, Sandhia Ponnarambil, Scott Caveney, Gun Almqvist, Monika Gołąbek, Linda Simonsson, Kaitlyn Lawson, Karin Bowen, Gene Colice, Jorge Lima Hetzel, Jussara Fiterman, Adelmir Souza Machado, Martti Anton Antila, Marina Andrade Lima, Suzana Erico Tanni Minamoto, Daniela Cavalet Blanco, Patricia Gomes de Matos Bezerra, Pierre-Alain Houle, Catherine Lemiere, Lyle S Melenka, Richard Leigh, Patrick Mitchell, Syed Anees, Bonavuth Pek, Guy Chouinard, Amarjit S Cheema, William Ho-Ching Yang, George Philteos, Pascal Chanez, Arnaud Bourdin, Gilles Devouassoux, Camille Taille, Frédéric De Blay, Christophe Leroyer, Antoine Beurnier, Gilles Garcia, Pierre-Olivier Girodet, François-Xavier Blanc, Antoine Magnan, Stéphanie Wanin, Jocelyne Just, Richard Linde, Stefan Zielen, Karin Förster, Christian Geßner, Margret Jandl, Roland Otto Buhl, Marc Oliver Kornmann, Anneliese Linnhoff, Andrea Ludwig-Sengpiel, Martin Ehlers, Tibor Schmoller, Heiner Steffen, Martin Hoffmann, Joachim Kirschner, Olaf Schmidt, Tobias Welte, Hilke Temme, Ori Wand, Amir Bar-Shai, Gabriel Izbicki, Neville Berkman, Gershon Fink, David Shitrit, Yochai Adir, Piotr Kuna, Barbara Rewerska, Ewa Pisarczyk-Bogacka, Oksana Kurbacheva, Sergey L Mikhailov, Maksim Vasilev, Alexander Emelyanov, Siraj Wali, Amr Albanna, Richard van Zyl-Smit, Ismail Abdullah, David Bernhardi, Farzana Hoosen, Elvis Irusen, Ismail Kalla, Deepak Lakha, Essack Mitha, Visvakuren Naidoo, Haylene Nell, Trevenesan Padayachee, Jeevren Reddy, Friedrich Petrick, Eugene van der Walt, Zubar Fazal Ahmed Vawda, Hae-Sim Park, Sang Haak Lee, Mi-Kyeong Kim, Jung-Won Park, You Sook Cho, Byung Jae Lee, Yoon-Seok Chang, Choon-Sik Park, Kwan Ho Lee, Sook Young Lee, HyoungKyu Yoon, Kyoung Hee Sohn, Myung Jae Park, Kyung Hoon Min, Young Joo Cho, Han Ki Park, YongChul Lee, Jaechun Lee, Chau-Chyun Sheu, Chih-Yen Tu, Kang-Yun Lee, Sevim Bavbek, Bilun Gemicioglu, Dane Ediger, Ilkay Koca Kalkan, Nataliia Makieieva, Mykola Ostrovskyy, Yevgeniya Dytyatkovs'ka, Yuriy Mykhaylovych Mostovoy, Kyrylo Lebed, Oleh Yakovenko, Atoya Adams, Timothy Mooring, Louis Torres Jr, Marvin Sexton, Ernest Thompson, Jonathan A Bernstein, Paul Lisi, Christopher M Chappel, Jeremy Cole, Gary I Greenwald, Conigliaro Jones, Ryan Mitchell Klein, David N Pham, Selwyn Spangenthal, Steven F Weinstein, Hugh H Windom, Neil L Kao, Mila A Leong, Vinay Mehta, Wendy C Moore, Saligrama Bhat, Bassil Aish, Steven M Meltzer, Mark H Moss, Edward M Kerwin, John Palsted Delgado, Gregg Hudson Lucksinger, Charles A Thompson, Sady A Alpizar, Sanjay Virgi Vadgama, Zahid Zafar, Joshua S Jacobs, NJira Lugogo, Neal Jain, Lawrence D Sher, Nabil S Andrawis, David Fuentes, Eric Jason Boren, Erika G Gonzalez, Neetu Talreja, Sheharyar Sandy Durrani, Sudhir Sekhsaria, Samuel DeLeon, Mayank Shukla, Martha M Totszollosy Tarpay, Faisal Fakih, Golda Hudes, Jeffrey P Tillinghast, Phillip E Korenblat, Kartik Shenoy, Loretta Que, Shahrukh Ahmad Kureishy, Fred Chukwuemeka Umeh, Vinh Nhu Nguyen, Hanh Thi Chu, and Thuy Thi Dieu Nguyen

Subjects
Pulmonary and Respiratory Medicine
Published
2023
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6. On the tangent Lie group of a symplectic Lie group

Author

David N. Pham

Subjects
Pure mathematics, Applied Mathematics, General Mathematics, Lie group, Tangent, Riemannian geometry, Omega, symbols.namesake, Iterated function, symbols, Vector field, Invariant (mathematics), Mathematics::Symplectic Geometry, Mathematics, Symplectic geometry
Abstract

Motivated by the recent work of Asgari and Salimi Moghaddam (Rend Circ Mat Palermo II Ser 67:185–195, 2018) on the Riemannian geometry of tangent Lie groups, we prove that the tangent Lie group $${ TG}$$ of a symplectic Lie group $$(G,\omega )$$ admits the structure of a symplectic Lie group. On $${ TG}$$, we construct a left invariant symplectic form $${\widetilde{\omega }}$$ which is induced from $$\omega $$ using complete and vertical lifts of left invariant vector fields on G. The aforementioned construction can be viewed as the symplectic analogue of the left invariant Riemannian metrics on the tangent Lie groups that were constructed in Asgari and Salimi Moghaddam (Rend Circ Mat Palermo II Ser 67:185–195, 2018). One immediate upshot of our construction is that by taking iterated tangent bundles of a non-abelian symplectic Lie group, one obtains a convenient means of generating non-abelian symplectic Lie groups of arbitrarily high dimension.

Published
2019
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7. The Changing Landscape for Stroke Prevention in AF

Author

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

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

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

Published
2017
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8. Bicovariant differential calculi for finite global quotients

Author

David N. Pham

Subjects
Pure mathematics, Mathematics::Commutative Algebra, General Mathematics, Mathematics::Quantum Algebra, Global quotients, noncommutative differential geometry, first order differential calculi, weak Hopf algebras, Differential (mathematics), Quotient, Mathematics
Abstract

Let ((M,G)) be a finite global quotient, that is, a finite set (M) with an action by a finite group $G$. In this note, we classify all bicovariant first order differential calculi (FODCs) over the weak Hopf algebra (Bbbk(Gltimes M)simeq Bbbk[Gltimes M]^ast), where (Gltimes M) is the action groupoid associated to ((M,G)), and (Bbbk[Gltimes M]) is the groupoid algebra of (Gltimes M). Specifically, we prove a necessary and sufficient condition for a FODC over (Bbbk(Gltimes M)) to be bicovariant and then show that the isomorphism classes of bicovariant FODCs over (Bbbk(Gltimes M)) are in one-to-one correspondence with subsets of a certain quotient space.

Published
2019

9. $\mathfrak{g}$-quasi-Frobenius Lie algebras

Author

David N. Pham

Subjects
Pure mathematics, Adjoint representation of a Lie algebra, Lie bialgebra, Mathematics::Category Theory, General Mathematics, Simple Lie group, Lie algebra, Adjoint representation, Killing form, Mathematics::Representation Theory, Lie conformal algebra, Mathematics, Graded Lie algebra
Abstract

A Lie version of Turaev’s $\overline{G}$-Frobenius algebras from 2-dimensional homotopy quantum field theory is proposed. The foundation for this Lie version is a structure we call a $\mathfrak{g}$-quasi-Frobenius Lie algebra for $\mathfrak{g}$ a finite dimensional Lie algebra. The latter consists of a quasi-Frobenius Lie algebra $(\mathfrak{q},\beta )$ together with a left $\mathfrak{g}$-module structure which acts on $\mathfrak{q}$ via derivations and for which $\beta $ is $\mathfrak{g}$-invariant. Geometrically, $\mathfrak{g}$-quasi-Frobenius Lie algebras are the Lie algebra structures associated to symplectic Lie groups with an action by a Lie group $G$ which acts via symplectic Lie group automorphisms. In addition to geometry, $\mathfrak{g}$-quasi-Frobenius Lie algebras can also be motivated from the point of view of category theory. Specifically, $\mathfrak{g}$-quasi Frobenius Lie algebras correspond to quasi Frobenius Lie objects in $\mathbf{Rep}(\mathfrak{g})$. If $\mathfrak{g}$ is now equipped with a Lie bialgebra structure, then the categorical formulation of $\overline{G}$-Frobenius algebras given in [16] suggests that the Lie version of a $\overline{G}$-Frobenius algebra is a quasi-Frobenius Lie object in $\mathbf{Rep}(D(\mathfrak{g}))$, where $D(\mathfrak{g})$ is the associated (semiclassical) Drinfeld double. We show that if $\mathfrak{g}$ is a quasitriangular Lie bialgebra, then every $\mathfrak{g}$-quasi-Frobenius Lie algebra has an induced $D(\mathfrak{g})$-action which gives it the structure of a $D(\mathfrak{g})$-quasi-Frobenius Lie algebra.

Published
2016
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10. The Lie groupoid analogue of a symplectic Lie group

Author

David N. Pham

Subjects
Lie algebroid, Mathematics - Differential Geometry, Pure mathematics, 22A22, 53D05, Fiber (mathematics), General Mathematics, Structure (category theory), Lie group, Lie groupoid, Differential Geometry (math.DG), Mathematics::K-Theory and Homology, Mathematics::Category Theory, Lie algebra, FOS: Mathematics, Mathematics::Symplectic Geometry, Mathematics, Symplectic manifold, Symplectic geometry
Abstract

A symplectic Lie group is a Lie group with a left-invariant symplectic form. Its Lie algebra structure is that of a quasi-Frobenius Lie algebra. In this note, we identify the groupoid analogue of a symplectic Lie group. We call the aforementioned structure a \textit{$t$-symplectic Lie groupoid}; the "$t$" is motivated by the fact that each target fiber of a $t$-symplectic Lie groupoid is a symplectic manifold. For a Lie groupoid $\mathcal{G}\rightrightarrows M$, we show that there is a one-to-one correspondence between quasi-Frobenius Lie algebroid structures on $A\mathcal{G}$ (the associated Lie algebroid) and $t$-symplectic Lie groupoid structures on $\mathcal{G}\rightrightarrows M$. In addition, we also introduce the notion of a \textit{symplectic Lie group bundle} (SLGB) which is a special case of both a $t$-symplectic Lie groupoid and a Lie group bundle. The basic properties of SLGBs are explored., Comment: 22 pages. Final version. To appear in Archivum Mathematicum

Published
2018
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11. Higher Affine Connections

Author

David N. Pham

Subjects
Mathematics - Differential Geometry, Tangent bundle, Pure mathematics, Multivector, 010308 nuclear & particles physics, Differential form, General Mathematics, 010102 general mathematics, FOS: Physical sciences, Mathematical Physics (math-ph), Bilinear form, Affine connection, 01 natural sciences, Covariant derivative, Differential Geometry (math.DG), 0103 physical sciences, FOS: Mathematics, Covariant transformation, Affine transformation, 0101 mathematics, Mathematical Physics, Mathematics
Abstract

For a smooth manifold $M$, it was shown in \cite{BPH} that every affine connection on the tangent bundle $TM$ naturally gives rise to covariant differentiation of multivector fields (MVFs) and differential forms along MVFs. In this paper, we generalize the covariant derivative of \cite{BPH} and construct covariant derivatives along MVFs which are not induced by affine connections on $TM$. We call this more general class of covariant derivatives \textit{higher affine connections}. In addition, we also propose a framework which gives rise to non-induced higher connections; this framework is obtained by equipping the full exterior bundle $\wedge^\bullet TM$ with an associative bilinear form $\eta$. Since the latter can be shown to be equivalent to a set of differential forms of various degrees, this framework also provides a link between higher connections and multisymplectic geometry., Comment: 37 pages; main definition and results generalized; substantial changes after section 4

Published
2015
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12. Increased matrix metalloproteinase-9 with elastolysis in nocturnal asthma

Author

Monica Kraft, David N. Pham, Richard J. Martin, and Hong Wei Chu

Subjects
Adult, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Pathology, Colorado, Time Factors, Biopsy, Statistics as Topic, Immunology, Bronchi, Matrix metalloproteinase, Forced Expiratory Volume, Internal medicine, medicine, Humans, Immunology and Allergy, Circadian rhythm, Asthma, biology, medicine.diagnostic_test, Bronchoscopy with Bronchoalveolar Lavage, business.industry, Respiratory disease, Tissue Inhibitor of Metalloproteinases, medicine.disease, Elastin, Respiratory Function Tests, Bronchoalveolar lavage, medicine.anatomical_structure, Endocrinology, Matrix Metalloproteinase 9, biology.protein, Female, business, Bronchoalveolar Lavage Fluid, Respiratory tract
Abstract

Background Matrix metalloproteinase-9 (MMP-9) is capable of degrading elastin, whereas tissue inhibitor of metalloproteinase-1 (TIMP-1) can inhibit MMP-9 activity. We observed reduced airway tissue elastin volume density in six subjects with nocturnal asthma (NA) as compared with seven subjects with nonnocturnal asthma (NNA) and seven normal controls (NL) when endobronchial biopsies were evaluated morphometrically at 4:00 pm and 4:00 am. Objective We hypothesized that increased metalloproteinases and decreased tissue inhibitors of metalloproteinases in the airways of subjects with NA may be responsible for reduced elastin volume density. Methods Ten additional subjects with NA, 10 subjects with NNA, and 7 normal control subjects underwent bronchoscopy with bronchoalveolar lavage at 4:00 pm and 4:00 am. Levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 were determined in bronchoalveolar lavage by enzyme-linked immunosorbent assay. Results There was a fourfold circadian increase in bronchoalveolar lavage levels of MMP-9, and there was a twofold increase in MMP-9:TIMP-1 ratio in NA subjects from 4:00 pm to 4:00 am. There were no circadian changes in the NNA and NL subjects. At 4:00 am, MMP-9 levels and the MMP-9:TIMP-1 ratio were highest in NA subjects. At 4:00 pm, no significant group differences were observed. The MMP-9 levels positively correlated with the overnight fall in forced expiratory volume in 1 second and the MMP-9/TIMP-1 ratio negatively correlated with the 4:00 am % predicted forced expiratory volume in 1 second. Conclusions Our results from these two pilot studies suggest that increased MMP-9 and decreased TIMP-1 at night in NA may lead to reduced elastin density.

Published
2003
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13. IL-4, IL-13, and dexamethasone augment fibroblast proliferation in asthma

Author

David N. Pham, Monica Kraft, Hong Wei Chu, and Christina C. Lewis

Subjects
Adult, Male, medicine.medical_specialty, Allergy, medicine.drug_class, medicine.medical_treatment, Immunology, Dexamethasone, Internal medicine, medicine, Immunology and Allergy, Humans, Fibroblast, Asthma, Interleukin-13, business.industry, Respiratory disease, Fibroblasts, medicine.disease, Cytokine, Endocrinology, medicine.anatomical_structure, Interleukin 13, Corticosteroid, Female, Interleukin-4, business, Cell Division, medicine.drug
Abstract

Background: IL-4 and IL-13 have been shown to be critical for expression of the asthma phenotype in a murine model and may modulate human fibroblast function. Objective: We hypothesized that IL-4 and IL-13 would increase airway fibroblast proliferation and reduce the ability of dexamethasone to decrease this proliferation. Methods: Six subjects with severe asthma, 5 subjects with mild asthma, and 5 healthy subjects underwent bronchoscopy with endobronchial biopsy. Biopsy specimens were placed in Dulbecco modified Eagle medium and cultured, and only fibro-blasts from the first and second passages were evaluated. Cells were incubated with IL-4 (50 ng/mL), IL-13 (10 ng/mL), and the combination for 48 hours in the presence and absence of dexamethasone, 10 –7 mol/L, and 10 –8 mol/L. Fibroblasts were also incubated with IFN-γ at 50 ng/mL to assess the response of a T H 1 cytokine on proliferation. Results: Fibroblast proliferation, determined by 3 H-thymidine incorporation, was significantly increased by IL-4 in subjects with mild asthma as compared with IL-4 in subjects with severe asthma and healthy subjects ( P = .003), IL-13 ( P = .011), and the combination ( P = .004). Dexamethasone also increased proliferation in the group with mild asthma as compared with the group with severe asthma and the healthy group (10 –7 mol/L, P = .02; 10 –8 mol/L, P = .02). IFN-γ did not significantly alter airway fibroblast proliferation. Conclusion: IL-4, IL-13, and dexamethasone all significantly increased fibroblast proliferation in subjects with mild asthma. (J Allergy Clin Immunol 2001;107:602-6.)

Published
2001

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