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2. Outcome of acute hypoxaemic respiratory failure: insights from the LUNG SAFE Study
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Pham, Tài, Pesenti, Antonio, Bellani, Giacomo, Rubenfeld, Gordon, Fan, Eddy, Bugedo, Guillermo, Lorente, José Angel, Fernandes, Antero do Vale, Van Haren, Frank, Bruhn, Alejandro, Rios, Fernando, Esteban, Andres, Gattinoni, Luciano, Larsson, Anders, McAuley, Daniel F., Ranieri, Marco, Thompson, B. Taylor, Wrigge, Hermann, Brochard, Laurent J., Laffey, John G, Antonio Pesenti, John G Laffey, Laurent Brochard, Andres Esteban, Luciano Gattinoni, Frank van Haren, Anders Larsson, Daniel F McAuley, Marco Ranieri, Gordon Rubenfeld, B Taylor Thompson, Hermann Wrigge, Arthur S Slutsky, Giacomo Bellani, Tài Pham, Eddy Fan, Fernando Rios, Thierry Sottiaux, Pieter Depuydt, Fredy S Lora, Luciano Cesar Azevedo, Guillermo Bugedo, Haibo Qiu, Marcos Gonzalez, Juan Silesky, Vladimir Cerny, Jonas Nielsen, Manuel Jibaja, Dimitrios Matamis, Jorge Luis Ranero, Pravin Amin, S M Hashemian, Kevin Clarkson, Kiyoyasu Kurahashi, Asisclo Villagomez, Amine Ali Zeggwagh, Leo M Heunks, Jon Henrik Laake, Jose Emmanuel Palo, Antero do Vale Fernandes, Dorel Sandesc, Yaasen Arabi, Vesna Bumbasierevic, Nicolas Nin, Jose A Lorente, Lise Piquilloud, Fekri Abroug, Lia McNamee, Javier Hurtado, Ed Bajwa, Gabriel Démpaire, Hektor Sula, Lordian Nunci, Alma Cani, Alan Zazu, Christian Dellera, Carolina S Insaurralde, Risso V Alejandro, Julio Daldin, Mauricio Vinzio, Ruben O Fernandez, Luis P Cardonnet, Lisandro R Bettini, Mariano Carboni Bisso, Emilio M Osman, Mariano G Setten, Pablo Lovazzano, Javier Alvarez, Veronica Villar, Norberto C Pozo, Nicolas Grubissich, Gustavo A Plotnikow, Daniela N Vasquez, Santiago Ilutovich, Norberto Tiribelli, Ariel Chena, Carlos A Pellegrini, María G Saenz, Elisa Estenssoro, Matias Brizuela, Hernan Gianinetto, Pablo E Gomez, Valeria I Cerrato, Marco G Bezzi, Silvina A Borello, Flavia A Loiacono, Adriana M Fernandez, Serena Knowles, Claire Reynolds, Deborah M Inskip, Jennene J Miller, Jing Kong, Christina Whitehead, Shailesh Bihari, Aylin Seven, Amanda Krstevski, Helen J Rodgers, Rebecca T Millar, Toni E McKenna, Irene M Bailey, Gabrielle C Hanlon, Anders Aneman, Joan M Lynch, Raman Azad, John Neal, Paul W Woods, Brigit L Roberts, Mark R Kol, Helen S Wong, Katharina C Riss, Thomas Staudinger, Xavier Wittebole, Caroline Berghe, Pierre A Bulpa, Alain M Dive, Rik Verstraete, Herve Lebbinck, Joris Vermassen, Philippe Meersseman, Helga Ceunen, Jonas I Rosa, Daniel O Beraldo, Claudio Piras, Adenilton M Rampinelli, Antonio P Nassar Jr, Sergio Mataloun, Marcelo Moock, Marlus M Thompson, Claudio H Gonçalves, Ana Carolina P Antônio, Aline Ascoli, Rodrigo S Biondi, Danielle C Fontenele, Danielle Nobrega, Vanessa M Sales, Ahmad Yazid Bin Hj Abul Wahab, Maizatul Ismail, Suresh Shindhe, John Laffey, Francois Beloncle, Kyle G Davies, Rob Cirone, Venika Manoharan, Mehvish Ismail, Ewan C Goligher, Mandeep Jassal, Erin Nishikawa, Areej Javeed, Gerard Curley, Nuttapol Rittayamai, Matteo Parotto, Niall D Ferguson, Sangeeta Mehta, Jenny Knoll, Antoine Pronovost, Sergio Canestrini, Alejandro R Bruhn, Patricio H Garcia, Felipe A Aliaga, Pamela A Farías, Jacob S Yumha, Claudia A Ortiz, Javier E Salas, Alejandro A Saez, Luis D Vega, Eduardo F Labarca, Felipe T Martinez, Nicolás G Carreño, Pilar Lora, Haitao Liu, Ling Liu, Rui Tang, Xiaoming Luo, Youzhong An, Huiying Zhao, Yan Gao, Zhe Zhai, Zheng L Ye, Wei Wang, Wenwen Li, Qingdong Li, Ruiqiang Zheng, Wenkui Yu, Juanhong Shen, Xinyu Li, Tao Yu, Weihua Lu, Ya Q Wu, Xiao B Huang, Zhenyang He, Yuanhua Lu, Hui Han, Fan Zhang, Renhua Sun, Hua X Wang, Shu H Qin, Bao H Zhu, Jun Zhao, Jian Liu, Bin Li, Jing L Liu, Fa C Zhou, Qiong J Li, Xing Y Zhang, Zhou Li-Xin, Qiang Xin-Hua, Liangyan Jiang, Yuan N Gao, Xian Y Zhao, Yuan Y Li, Xiao L Li, Chunting Wang, Qingchun Yao, Rongguo Yu, Kai Chen, Huanzhang Shao, Bingyu Qin, Qing Q Huang, Wei H Zhu, Ai Y Hang, Ma X Hua, Yimin Li, Yonghao Xu, Yu D Di, Long L Ling, Tie H Qin, Shou H Wang, Junping Qin, Yi Han, Suming Zhou, Monica P Vargas, Juan I Silesky Jimenez, Manuel A González Rojas, Jaime E SolisQuesada, Christian M Ramirez-Alfaro, Jan Máca, Peter Sklienka, Jakob Gjedsted, Aage Christiansen, Boris G Villamagua, Iguel Llano, Philippe Burtin, Gautier Buzancais, Pascal Beuret, Nicolas Pelletier, Satar Mortaza, Alain Mercat, Jonathan Chelly, Sébastien Jochmans, Nicolas Terzi, Cédric Daubin, Guillaume Carteaux, Nicolas de Prost, Jean-Daniel Chiche, Fabrice Daviaud, Muriel Fartoukh, Guillaume Barberet, Jerome Biehler, Jean Dellamonica, Denis Doyen, Jean-Michel Arnal, Anais Briquet, Sami Hraiech, Laurent Papazian, Arnaud Follin, Damien Roux, Jonathan Messika, Evangelos Kalaitzis, Laurence Dangers, Alain Combes, Siu-Ming Au, Gaetan Béduneau, Dorothée Carpentier, Elie H Zogheib, Herve Dupont, Sylvie Ricome, Francesco L Santoli, Sebastien L Besset, Philippe Michel, Bruno Gelée, Pierre-Eric Danin, Bernard Goubaux, Philippe J Crova, Nga T Phan, Frantz Berkelmans, Julio C Badie, Romain Tapponnier, Josette Gally, Samy Khebbeb, Jean-Etienne Herbrecht, Francis Schneider, PierreLouis M Declercq, Jean-Philippe Rigaud, Jacques Duranteau, Anatole Harrois, Russell Chabanne, Julien Marin, Charlene Bigot, Sandrine Thibault, Mohammed Ghazi, Messabi Boukhazna, Salem Ould Zein, Jack R Richecoeur, Daniele M Combaux, Fabien Grelon, Charlene Le Moal, Elise P Sauvadet, Adrien Robine, Virginie Lemiale, Danielle Reuter, Martin Dres, Alexandre Demoule, Dany Goldgran-Toledano, Loredana Baboi, Claude Guérin, Ralph Lohner, Jens Kraßler, Susanne Schäfer, Kai D Zacharowski, Patrick Meybohm, Andreas W Reske, Philipp Simon, HansBernd F Hopf, Michael Schuetz, Thomas Baltus, Metaxia N Papanikolaou, Theonymfi G Papavasilopoulou, Giannis A Zacharas, Vasilis Ourailogloy, Eleni K Mouloudi, Eleni V Massa, Eva O Nagy, Electra E Stamou, Ellada V Kiourtzieva, Marina A Oikonomou, Luis E Avila, Cesar A Cortez, Johanna E Citalán, Sameer A Jog, Safal D Sable, Bhagyesh Shah, Mohan Gurjar, Arvind K Baronia, Mohammedfaruk Memon, Radhakrishnan Muthuchellappan, Venkatapura J Ramesh, Anitha Shenoy, Ramesh Unnikrishnan, Subhal B Dixit, Rachana V Rhayakar, Nagarajan Ramakrishnan, Vallish K Bhardwaj, Heera L Mahto, Sudha V Sagar, Vijayanand Palaniswamy, Deeban Ganesan, Seyed Mohammadreza Hashemian, Hamidreza Jamaati, Farshad Heidari, Edel A Meaney, Alistair Nichol, Karl M Knapman, Donall O'Croinin, Eimhin S Dunne, Dorothy M Breen, Kevin P Clarkson, Rola F Jaafar, Rory Dwyer, Fahd Amir, Olaitan O Ajetunmobi, Aogan C O'Muircheartaigh, Colin S Black, Nuala Treanor, Daniel V Collins, Wahid Altaf, Gianluca Zani, Maurizio Fusari, Savino Spadaro, Carlo A Volta, Romano Graziani, Barbara Brunettini, Salvatore Palmese, Paolo Formenti, Michele Umbrello, Andrea Lombardo, Elisabetta Pecci, Marco Botteri, Monica Savioli, Alessandro Protti, Alessia Mattei, Lorenzo Schiavoni, Andrea Tinnirello, Manuel Todeschini, Antonino Giarratano, Andrea Cortegiani, Massimo M Antonelli, Luca M Montini, Paolo Casalena, Sergio Scafetti, Giovanna Panarello, Giovanna Occhipinti, Nicolò Patroniti, Matteo Pozzi, Roberto R Biscione, Michela M Poli, Ferdinando Raimondi, Daniela Albiero, Giulia Crapelli, Eduardo Beck, Vincenzo Pota, Vincenzo Schiavone, Alexandre Molin, Fabio Tarantino, Giacomo Monti, Elena Frati, Lucia Mirabella, Gilda Cinnella, Tommaso Fossali, Riccardo Colombo, Pierpaolo Terragni, Ilaria Pattarino, Francesco Mojoli, Antonio Braschi, Erika E Borotto, Andrea N Cracchiolo, Daniela M Palma, Francesco Raponi, Giuseppe Foti, Ettore R Vascotto, Andrea Coppadoro, Luca Brazzi, Leda Floris, Giorgio A Iotti, Aaron Venti, Osamu Yamaguchi, Shunsuke Takagi, Hiroki N Maeyama, Eizo Watanabe, Yoshihiro Yamaji, Kazuyoshi Shimizu, Kyoko Shiozaki, Satoru Futami, Sekine Ryosuke, Koji Saito, Yoshinobu Kameyama, Keiko Ueno, Masayo Izawa, Nao Okuda, Hiroyuki Suzuki, Tomofumi Harasawa, Michitaka Nasu, Tadaaki Takada, Fumihito Ito, Shin Nunomiya, Kansuke Koyama, Toshikazu Abe, Kohkichi Andoh, Kohei Kusumoto, Akira Hirata, Akihiro Takaba, Hiroyasu Kimura, Shuhei Matsumoto, Ushio Higashijima, Hiroyuki Honda, Nobumasa Aoki, Hiroshi Imai, Yasuaki Ogino, Ichiko Mizuguchi, Kazuya Ichikado, Kenichi Nitta, Katsunori Mochizuki, Tomoaki Hashida, Hiroyuki Tanaka, Tomoyuki Nakamura, Daisuke Niimi, Takeshi Ueda, Yozo Kashiwa, Akinori Uchiyama, Olegs Sabelnikovs, Peteris Oss, Youssef Haddad, Kong Y Liew, Silvio A Ñamendys-Silva, Yves D Jarquin-Badiola, Luis A Sanchez-Hurtado, Saira S Gomez-Flores, Maria C Marin, Asisclo J Villagomez, Jordana S Lemus, Jonathan M Fierro, Mavy Ramirez Cervantes, Francisco Javier Flores Mejia, Dulce Dector, Alejandro Rojas, Daniel R Gonzalez, Claudia R Estrella, Jorge R Sanchez-Medina, Alvaro Ramirez-Gutierrez, Fernando G George, Janet S Aguirre, Juan A Buensuseso, Manuel Poblano, Tarek Dendane, Hicham Balkhi, Mina Elkhayari, Nacer Samkaoui, Hanane Ezzouine, Abdellatif Benslama, Mourad Amor, Wajdi Maazouzi, Nedim Cimic, Oliver Beck, Monique M Bruns, Jeroen A Schouten, Myra Rinia, Monique Raaijmakers, Hellen M van Wezel, Serge J Heines, Ulrich Strauch, Marc P Buise, Fabienne D Simonis, Marcus J Schultz, Jennifer C Goodson, Troy S Browne, Leanlove Navarra, Anna Hunt, Robyn A Hutchison, Mathew B Bailey, Lynette Newby, Colin McArthur, Michael Kalkoff, Alex Mcleod, Jonathan Casement, Danielle J Hacking, Finn H Andersen, Merete S Dolva, Jon H Laake, Andreas Barratt-Due, Kim Andre L Noremark, Eldar Søreide, Brit Å Sjøbø, Anne B Guttormsen, Hector H Leon Yoshido, Ronald Zumaran Aguilar, Fredy A Montes Oscanoa, Alain U Alisasis, Joanne B Robles, Rossini Abbie B Pasanting-Lim, Beatriz C Tan, Pawel Andruszkiewicz, Karina Jakubowska, Cristina M Coxo, António M Alvarez, Bruno S Oliveira, Gustavo M Montanha, Nelson C Barros, Carlos S Pereira, António M Messias, Jorge M Monteiro, Ana M Araujo, Nuno T Catorze, Susan M Marum, Maria J Bouw, Rui M Gomes, Vania A Brito, Silvia Castro, Joana M Estilita, Filipa M Barros, Isabel M Serra, Aurelia M Martinho, Dana R Tomescu, Alexandra Marcu, Ovidiu H Bedreag, Marius Papurica, Dan E Corneci, Silvius Ioan Negoita, Evgeny Grigoriev, Alexey I Gritsan, Andrey A Gazenkampf, Ghaleb Almekhlafi, Mohamad M Albarrak, Ghanem M Mustafa, Khalid A Maghrabi, Nawal Salahuddin, Tharwat M Aisa, Ahmed S Al Jabbary, Edgardo Tabhan, Yaseen M Arabi, Olivia A Trinidad, Hasan M Al Dorzi, Edgardo E Tabhan, Vesna Bumbasirevic, Bojan Jovanovic, Stefan Bolon, Oliver Smith, Jordi Mancebo, Hernan Aguirre-Bermeo, Juan C Lopez-Delgado, Francisco Esteve, Gemma Rialp, Catalina Forteza, Candelaria De Haro, Antonio Artigas, Guillermo M Albaiceta, Sara De Cima-Iglesias, Leticia Seoane-Quiroga, Alexandra Ceniceros-Barros, Antonio L RuizAguilar, Luis M Claraco-Vega, Juan Alfonso Soler, Maria Del Carmen Lorente, Cecilia Hermosa, Federico Gordo, Miryam PrietoGonzález, Juan B López-Messa, Manuel P Perez, Cesar P Perez, Raquel Montoiro Allue, Ferran RocheCampo, Marcos Ibañez-Santacruz, Susana TempranoSusana, Maria C Pintado, Raul De Pablo, Pilar Ricart Aroa Gómez, Silvia Rodriguez Ruiz, Silvia Iglesias Moles, Mª Teresa Jurado, Alfons Arizmendi, Enrique A Piacentini, Nieves Franco, Teresa Honrubia, Meisy Perez Cheng, Elena Perez Losada, Javier Blanco, Luis J Yuste, Cecilia Carbayo-Gorriz, Francisca G Cazorla-Barranquero, Javier G Alonso, Rosa S Alda, Ángela Algaba, Gonzalo Navarro, Enrique Cereijo, Esther Diaz-Rodriguez, Diego Pastor Marcos, Laura Alvarez Montero, Luis Herrera Para, Roberto Jimenez Sanchez, Miguel Angel Blasco Navalpotro, Ricardo Diaz Abad, Raquel Montiel González, Dácil Parrilla Toribio, Alejandro G Castro, Maria Jose D Artiga, Oscar Penuelas, Tomas P Roser, Moreno F Olga, Elena Gallego Curto, Rocío Manzano Sánchez, Vallverdu P Imma, Garcia M Elisabet, Laura Claverias, Monica Magret, Ana M Pellicer, Lucia L Rodriguez, Jesús Sánchez-Ballesteros, Ángela González-Salamanca, Antonio G Jimenez, Francisco P Huerta, Juan Carlos J Sotillo Diaz, Esther Bermejo Lopez, David D Llinares Moya, Alec A Tallet Alfonso, Palazon Sanchez Eugenio Luis, Palazon Sanchez Cesar, Sánchez I Rafael, Corcoles G Virgilio, Noelia N Recio, Christian C Rylander, Bernhard Holzgraefe, Lars M Broman, Joanna Wessbergh, Linnea Persson, Fredrik Schiöler, Hans Kedelv, Anna Oscarsson Tibblin, Henrik Appelberg, Lars Hedlund, Johan Helleberg, Karin E Eriksson, Rita Glietsch, Niklas Larsson, Ingela Nygren, Silvia L Nunes, Anna-Karin Morin, Thomas Kander, Anne Adolfsson, Hervé O Zender, Corinne Leemann-Refondini, Souheil Elatrous, Slaheddine Bouchoucha, Imed Chouchene, Islem Ouanes, Asma Ben Souissi, Salma Kamoun, Oktay Demirkiran, Mustafa Aker, Emre Erbabacan, Ilkay Ceylan, Nermin Kelebek Girgin, Menekse Ozcelik, Necmettin Ünal, Basak Ceyda Meco, Onat O Akyol, Suleyman S Derman, Barry Kennedy, Ken Parhar, Latha Srinivasa, Danny McAuley, Phil Hopkins, Clare Mellis, Vivek Kakar, Dan Hadfield, Andre Vercueil, Kaushik Bhowmick, Sally K Humphreys, Andrew Ferguson, Raymond Mckee, Ashok S Raj, Danielle A Fawkes, Philip Watt, Linda Twohey, Rajeev R Jha, Matthew Thomas, Alex Morton, Varsha Kadaba, Mark J Smith, Anil P Hormis, Santhana G Kannan, Miriam Namih, Henrik Reschreiter, Julie Camsooksai, Alek Kumar, Szabolcs Rugonfalvi, Christopher Nutt, Orla Oneill, Colette Seasman, Ged Dempsey, Christopher J Scott, Helen E Ellis, Stuart Mckechnie, Paula J Hutton, Nora N Di Tomasso, Michela N Vitale, Ruth O Griffin, Michael N Dean, Julius H Cranshaw, Emma L Willett, Nicholas Ioannou, Sarah Gillis, Peter Csabi, Rosaleen Macfadyen, Heidi Dawson, Pieter D Preez, Alexandra J Williams, Owen Boyd, Laura Ortiz-Ruiz de Gordoa, Jon Bramall, Sophie Symmonds, Simon K Chau, Tim Wenham, Tamas Szakmany, Piroska Toth-Tarsoly, Katie H McCalman, Peter Alexander, Lorraine Stephenson, Thomas Collyer, Rhiannon Chapman, Raphael Cooper, Russell M Allan, Malcolm Sim, David W Wrathall, Donald A Irvine, Kim S Zantua, John C Adams, Andrew J Burtenshaw, Gareth P Sellors, Ingeborg D Welters, Karen E Williams, Robert J Hessell, Matthew G Oldroyd, Ceri E Battle, Suresh Pillai, Istvan Kajtor, Mageswaran Sivashanmugavel, Sinead C Okane, Adrian Donnelly, Aniko D Frigyik, Jon P Careless, Martin M May, Richard Stewart, T John Trinder, Samantha J Hagan, Jade M Cole, Caroline C MacFie, Anna T Dowling, Nicolás Nin, Edgardo Nuñez, Gustavo Pittini, Ruben Rodriguez, María C Imperio, Cristina Santos, Ana G França, Alejandro Ebeid, Alberto Deicas, Carolina Serra, Aditya Uppalapati, Ghassan Kamel, Valerie M Banner-Goodspeed, Jeremy R Beitler, Satyanarayana Reddy Mukkera, Shreedhar Kulkarni, John O Shinn Iii, Dina Gomaa, Christopher Tainter, Jarone Lee, Tomaz MesarJarone Lee, Dale J Yeatts, Jessica Warren, Michael J Lanspa, Russel R Miller, Colin K Grissom, Samuel M Brown, Philippe R Bauer, Ryan J Gosselin, Barrett T Kitch, Jason E Cohen, Scott H Beegle, Shazia Choudry, Renaud M Gueret, Aiman Tulaimat, William Stigler, Hitesh Batra, Nidhi G Huff, Keith D Lamb, Trevor W Oetting, Nicholas M Mohr, Claine Judy, Shigeki Saito, Fayez M Kheir, Fayez Kheir, Adam B Schlichting, Angela Delsing, Daniel R Crouch, Mary Elmasri, Dina Ismail, Kyle R Dreyer, Thomas C Blakeman, Rebecca M Baro, Carolina Quintana Grijalba, Peter C Hou, Raghu Seethala, Imo Aisiku, Galen Henderson, Gyorgy Frendl, Sen-Kuang Hou, Robert L Owens, Ashley Schomer, Pham, Tài, Pesenti, Antonio, Bellani, Giacomo, Rubenfeld, Gordon, Fan, Eddy, Bugedo, Guillermo, Lorente, José Angel, Fernandes, Antero do Vale, Van Haren, Frank, Bruhn, Alejandro, Rios, Fernando, Esteban, Andre, Gattinoni, Luciano, Larsson, Ander, McAuley, Daniel F., Ranieri, Marco, Thompson, B. Taylor, Wrigge, Hermann, Brochard, Laurent J., Laffey, John G, Antonio Pesenti, John G Laffey, Laurent Brochard, Andres Esteban, Luciano Gattinoni, Frank van Haren, Anders Larsson, Daniel F McAuley, Marco Ranieri, Gordon Rubenfeld, B Taylor Thompson, Hermann Wrigge, Arthur S Slutsky, John G Laffey, Giacomo Bellani, Tài Pham, Eddy Fan, Fernando Rios, Frank van Haren, Thierry Sottiaux, Pieter Depuydt, Fredy S Lora, Luciano Cesar Azevedo, Eddy Fan, Guillermo Bugedo, Haibo Qiu, Marcos Gonzalez, Juan Silesky, Vladimir Cerny, Jonas Nielsen, Manuel Jibaja, Tài Pham, Hermann Wrigge, Dimitrios Matamis, Jorge Luis Ranero, Pravin Amin, S M Hashemian, Kevin Clarkson, Giacomo Bellani, Kiyoyasu Kurahashi, Asisclo Villagomez, Amine Ali Zeggwagh, Leo M Heunks, Jon Henrik Laake, Jose Emmanuel Palo, Antero do Vale Fernandes, Dorel Sandesc, Yaasen Arabi, Vesna Bumbasierevic, Nicolas Nin, Jose A Lorente, Anders Larsson, Lise Piquilloud, Fekri Abroug, Daniel F McAuley, Lia McNamee, Javier Hurtado, Ed Bajwa, Gabriel Démpaire, Hektor Sula, Lordian Nunci, Alma Cani, Alan Zazu, Christian Dellera, Carolina S Insaurralde, Risso V Alejandro, Julio Daldin, Mauricio Vinzio, Ruben O Fernandez, Luis P Cardonnet, Lisandro R Bettini, Mariano Carboni Bisso, Emilio M Osman, Mariano G Setten, Pablo Lovazzano, Javier Alvarez, Veronica Villar, Norberto C Pozo, Nicolas Grubissich, Gustavo A Plotnikow, Daniela N Vasquez, Santiago Ilutovich, Norberto Tiribelli, Ariel Chena, Carlos A Pellegrini, María G Saenz, Elisa Estenssoro, Matias Brizuela, Hernan Gianinetto, Pablo E Gomez, Valeria I Cerrato, Marco G Bezzi, Silvina A Borello, Flavia A Loiacono, Adriana M Fernandez, Serena Knowles, Claire Reynolds, Deborah M Inskip, Jennene J Miller, Jing Kong, Christina Whitehead, Shailesh Bihari, Aylin Seven, Amanda Krstevski, Helen J Rodgers, Rebecca T Millar, Toni E McKenna, Irene M Bailey, Gabrielle C Hanlon, Anders Aneman, Joan M Lynch, Raman Azad, John Neal, Paul W Woods, Brigit L Roberts, Mark R Kol, Helen S Wong, Katharina C Riss, Thomas Staudinger, Xavier Wittebole, Caroline Berghe, Pierre A Bulpa, Alain M Dive, Rik Verstraete, Herve Lebbinck, Pieter Depuydt, Joris Vermassen, Philippe Meersseman, Helga Ceunen, Jonas I Rosa, Daniel O Beraldo, Claudio Piras, Adenilton M Rampinelli, Antonio P Nassar Jr, Sergio Mataloun, Marcelo Moock, Marlus M Thompson, Claudio H Gonçalves, Ana Carolina P Antônio, Aline Ascoli, Rodrigo S Biondi, Danielle C Fontenele, Danielle Nobrega, Vanessa M Sales, Ahmad Yazid Bin Hj Abul Wahab, Maizatul Ismail, Suresh Shindhe, John Laffey, Francois Beloncle, Kyle G Davies, Rob Cirone, Venika Manoharan, Mehvish Ismail, Ewan C Goligher, Mandeep Jassal, Erin Nishikawa, Areej Javeed, Gerard Curley, Nuttapol Rittayamai, Matteo Parotto, Niall D Ferguson, Sangeeta Mehta, Jenny Knoll, Antoine Pronovost, Sergio Canestrini, Alejandro R Bruhn, Patricio H Garcia, Felipe A Aliaga, Pamela A Farías, Jacob S Yumha, Claudia A Ortiz, Javier E Salas, Alejandro A Saez, Luis D Vega, Eduardo F Labarca, Felipe T Martinez, Nicolás G Carreño, Pilar Lora, Haitao Liu, Haibo Qiu, Ling Liu, Rui Tang, Xiaoming Luo, Youzhong An, Huiying Zhao, Yan Gao, Zhe Zhai, Zheng L Ye, Wei Wang, Wenwen Li, Qingdong Li, Ruiqiang Zheng, Wenkui Yu, Juanhong Shen, Xinyu Li, Tao Yu, Weihua Lu, Ya Q Wu, Xiao B Huang, Zhenyang He, Yuanhua Lu, Hui Han, Fan Zhang, Renhua Sun, Hua X Wang, Shu H Qin, Bao H Zhu, Jun Zhao, Jian Liu, Bin Li, Jing L Liu, Fa C Zhou, Qiong J Li, Xing Y Zhang, Zhou Li-Xin, Qiang Xin-Hua, Liangyan Jiang, Yuan N Gao, Xian Y Zhao, Yuan Y Li, Xiao L Li, Chunting Wang, Qingchun Yao, Rongguo Yu, Kai Chen, Huanzhang Shao, Bingyu Qin, Qing Q Huang, Wei H Zhu, Ai Y Hang, Ma X Hua, Yimin Li, Yonghao Xu, Yu D Di, Long L Ling, Tie H Qin, Shou H Wang, Junping Qin, Yi Han, Suming Zhou, Monica P Vargas, Juan I Silesky Jimenez, Manuel A González Rojas, Jaime E SolisQuesada, Christian M Ramirez-Alfaro, Jan Máca, Peter Sklienka, Jakob Gjedsted, Aage Christiansen, Jonas Nielsen, Boris G Villamagua, Iguel Llano, Philippe Burtin, Gautier Buzancais, Pascal Beuret, Nicolas Pelletier, Satar Mortaza, Alain Mercat, Jonathan Chelly, Sébastien Jochmans, Nicolas Terzi, Cédric Daubin, Guillaume Carteaux, Nicolas de Prost, Jean-Daniel Chiche, Fabrice Daviaud, Tài Pham, Muriel Fartoukh, Guillaume Barberet, Jerome Biehler, Jean Dellamonica, Denis Doyen, Jean-Michel Arnal, Anais Briquet, Sami Hraiech, Laurent Papazian, Arnaud Follin, Damien Roux, Jonathan Messika, Evangelos Kalaitzis, Laurence Dangers, Alain Combes, Siu-Ming Au, Gaetan Béduneau, Dorothée Carpentier, Elie H Zogheib, Herve Dupont, Sylvie Ricome, Francesco L Santoli, Sebastien L Besset, Philippe Michel, Bruno Gelée, Pierre-Eric Danin, Bernard Goubaux, Philippe J Crova, Nga T Phan, Frantz Berkelmans, Julio C Badie, Romain Tapponnier, Josette Gally, Samy Khebbeb, Jean-Etienne Herbrecht, Francis Schneider, PierreLouis M Declercq, Jean-Philippe Rigaud, Jacques Duranteau, Anatole Harrois, Russell Chabanne, Julien Marin, Charlene Bigot, Sandrine Thibault, Mohammed Ghazi, Messabi Boukhazna, Salem Ould Zein, Jack R Richecoeur, Daniele M Combaux, Fabien Grelon, Charlene Le Moal, Elise P Sauvadet, Adrien Robine, Virginie Lemiale, Danielle Reuter, Martin Dres, Alexandre Demoule, Dany Goldgran-Toledano, Loredana Baboi, Claude Guérin, Ralph Lohner, Jens Kraßler, Susanne Schäfer, Kai D Zacharowski, Patrick Meybohm, Andreas W Reske, Philipp Simon, HansBernd F Hopf, Michael Schuetz, Thomas Baltus, Metaxia N Papanikolaou, Theonymfi G Papavasilopoulou, Giannis A Zacharas, Vasilis Ourailogloy, Eleni K Mouloudi, Eleni V Massa, Eva O Nagy, Electra E Stamou, Ellada V Kiourtzieva, Marina A Oikonomou, Luis E Avila, Cesar A Cortez, Johanna E Citalán, Sameer A Jog, Safal D Sable, Bhagyesh Shah, Mohan Gurjar, Arvind K Baronia, Mohammedfaruk Memon, Radhakrishnan Muthuchellappan, Venkatapura J Ramesh, Anitha Shenoy, Ramesh Unnikrishnan, Subhal B Dixit, Rachana V Rhayakar, Nagarajan Ramakrishnan, Vallish K Bhardwaj, Heera L Mahto, Sudha V Sagar, Vijayanand Palaniswamy, Deeban Ganesan, Seyed Mohammadreza Hashemian, Hamidreza Jamaati, Farshad Heidari, Edel A Meaney, Alistair Nichol, Karl M Knapman, Donall O'Croinin, Eimhin S Dunne, Dorothy M Breen, Kevin P Clarkson, Rola F Jaafar, Rory Dwyer, Fahd Amir, Olaitan O Ajetunmobi, Aogan C O'Muircheartaigh, Colin S Black, Nuala Treanor, Daniel V Collins, Wahid Altaf, Gianluca Zani, Maurizio Fusari, Savino Spadaro, Carlo A Volta, Romano Graziani, Barbara Brunettini, Salvatore Palmese, Paolo Formenti, Michele Umbrello, Andrea Lombardo, Elisabetta Pecci, Marco Botteri, Monica Savioli, Alessandro Protti, Alessia Mattei, Lorenzo Schiavoni, Andrea Tinnirello, Manuel Todeschini, Antonino Giarratano, Andrea Cortegiani, Massimo M Antonelli, Luca M Montini, Paolo Casalena, Sergio Scafetti, Giovanna Panarello, Giovanna Occhipinti, Nicolò Patroniti, Matteo Pozzi, Roberto R Biscione, Michela M Poli, Ferdinando Raimondi, Daniela Albiero, Giulia Crapelli, Eduardo Beck, Vincenzo 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Adrian Donnelly, Aniko D Frigyik, Jon P Careless, Martin M May, Richard Stewart, T John Trinder, Samantha J Hagan, Jade M Cole, Caroline C MacFie, Anna T Dowling, Javier Hurtado, Nicolás Nin, Javier Hurtado, Edgardo Nuñez, Gustavo Pittini, Ruben Rodriguez, María C Imperio, Cristina Santos, Ana G França, Alejandro Ebeid, Alberto Deicas, Carolina Serra, Aditya Uppalapati, Ghassan Kamel, Valerie M Banner-Goodspeed, Jeremy R Beitler, Satyanarayana Reddy Mukkera, Shreedhar Kulkarni, John O Shinn Iii, Dina Gomaa, Christopher Tainter, Jarone Lee, Tomaz MesarJarone Lee, Dale J Yeatts, Jessica Warren, Michael J Lanspa, Russel R Miller, Colin K Grissom, Samuel M Brown, Philippe R Bauer, Ryan J Gosselin, Barrett T Kitch, Jason E Cohen, Scott H Beegle, Shazia Choudry, Renaud M Gueret, Aiman Tulaimat, William Stigler, Hitesh Batra, Nidhi G Huff, Keith D Lamb, Trevor W Oetting, Nicholas M Mohr, Claine Judy, Shigeki Saito, Fayez M Kheir, Fayez Kheir, Adam B Schlichting, Angela Delsing, Daniel R Crouch, Mary Elmasri, Daniel R Crouch, Dina Ismail, Kyle R Dreyer, Thomas C Blakeman, Dina Gomaa, Rebecca M Baro, Carolina Quintana Grijalba, Peter C Hou, Raghu Seethala, Imo Aisiku, Galen Henderson, Gyorgy Frendl, Sen-Kuang Hou, Robert L Owens, Ashley Schomer, Intensive Care Medicine, ACS - Diabetes & metabolism, ACS - Pulmonary hypertension & thrombosis, ACS - Microcirculation, Pham, T, Pesenti, A, Bellani, G, Rubenfeld, G, Fan, E, Bugedo, G, Lorente, J, Fernandes, A, Van Haren, F, Bruhn, A, Rios, F, Esteban, A, Gattinoni, L, Larsson, A, Mcauley, D, Ranieri, M, Thompson, B, Wrigge, H, Brochard, L, Laffey, J, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), St. Michael's Hospital, University of Toronto, Groupe de recherche clinique CARMAS, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Università degli Studi di Milano [Milano] (UNIMI), University of Milan, San Gerardo Hospital, Sunnybrook Health Sciences Center, Mount Sinai Hospital [Toronto, Canada] (MSH), Pontificia Universidad Católica de Chile (UC), University Hospital of Getafe, CIBER Enfermedades Respiratorias (CIBERES), Universidad Europea de Madrid, Hospital Garcia de Orta (EPE), Canberra Hospital, Medical School [Australian National University - ANU], Australian National University (ANU), University of Canberra, Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), University of Göttingen - Georg-August-Universität Göttingen, Uppsala University, Queen's University [Belfast] (QUB), Royal Victoria Hospital, McGill University Health Center [Montreal] (MUHC), Università degli Studi di Bologna, Massachusetts General Hospital [Boston], University Hospital Leipzig, Department of Anaesthesiology, Intensive Care and Emergency Medicine, Pain Therapy, Bergmannstrost Hospital Halle, 06112, Halle, National University of Ireland [Galway] (NUI Galway), Bayer GlaxoSmithKline, GSK Baxter International Boehringer Ingelheim Wellcome Trust, WT National Institute for Health Research, NIHR Queen's University Belfast, QUB Medical Research Council Canada, MRC European Society of Intensive Care Medicine, ESICM, Support statement: This work was supported by the European Society of Intensive Care Medicine. Funding information for this article has been deposited with the Crossref Funder Registry., Conflict of interest: T. Pham has nothing to disclose. A. Pesenti reports personal fees from Maquet, Novalung/Xenios, Baxter, Gilead and Boehringer Ingelheim, outside the submitted work. G. Bellani reports grants and personal fees from Draeger Medical, personal fees from Getinge, Hamilton, GE Healthcare, Dimar SRL, Intersurgical and Flowmeter SPA, outside the submitted work. G. Rubenfeld has nothing to disclose. E. Fan reports personal fees from ALung Technologies, Getinge and MC3 Cardiopulmonary, grants, personal fees and non-financial support from Fresenius Medical Care, outside the submitted work. G. Bugedo has nothing to disclose. J.A. Lorente has nothing to disclose. A.D. V. Fernandes has nothing to disclose. F. Van Haren has nothing to disclose. A. Bruhn has nothing to disclose. F. Rios has nothing to disclose. A. Esteban has nothing to disclose. L. Gattinoni has nothing to disclose. A. Larsson reports grants from the Swedish Heart and Lung Foundation, during the conduct of the study. D.F. McAuley reports personal fees from consultancy for GlaxoSmithKline, Boehringer Ingelheim and Bayer, outside the submitted work, in addition, his institution has received funds from grants from the UK NIHR, Wellcome Trust, Innovate UK, NI HSC R&D Division, NI Chest Heart and Stroke, and MRC, is one of four named inventors on a patent US8962032 covering the use of sialic acid-bearing nanoparticles as anti-inflammatory agents issued to his institution, The Queen’s University of Belfast (http://www.google.com/patents/US8962032), and is a Director of Research for the Intensive Care Society and NIHR EME Programme Director. M. Ranieri has nothing to disclose. B.T. Thompson reports personal fees from Bayer, Thetis and Novartis, outside the submitted work. H. Wrigge reports personal fees for consultancy from Dräger Medical, personal fees for advisory board work from Liberate Medical, grants and personal fees for lectures from InfectoPharm, personal fees for lectures from MSD and GE, outside the submitted work. L.J. Brochard reports grants from Medtronic Covidien, grants and non-financial support from Fisher Paykel, non-financial support from Air Liquide, Sentec and Philips, other (patent) from General Electric, outside the submitted work. J.G. Laffey reports grants and personal fees from Baxter, grants and non-financial support from Aerogen and Factor Biosciences, outside the submitted work., LUNG SAFE Investigators and the European Society of Intensive Care Medicine Trials Group: Antonio Pesenti, John G Laffey, Laurent Brochard, Andres Esteban, Luciano Gattinoni, Frank van Haren, Anders Larsson, Daniel F McAuley, Marco Ranieri, Gordon Rubenfeld, B Taylor Thompson, Hermann Wrigge, Arthur S Slutsky, John G Laffey, Giacomo Bellani, Tài Pham, Eddy Fan, Fernando Rios, Frank van Haren, Thierry Sottiaux, Pieter Depuydt, Fredy S Lora, Luciano Cesar Azevedo, Eddy Fan, Guillermo Bugedo, Haibo Qiu, Marcos Gonzalez, Juan Silesky, Vladimir Cerny, Jonas Nielsen, Manuel Jibaja, Tài Pham, Hermann Wrigge, Dimitrios Matamis, Jorge Luis Ranero, Pravin Amin, S M Hashemian, Kevin Clarkson, Giacomo Bellani, Kiyoyasu Kurahashi, Asisclo Villagomez, Amine Ali Zeggwagh, Leo M Heunks, Jon Henrik Laake, Jose Emmanuel Palo, Antero do Vale Fernandes, Dorel Sandesc, Yaasen Arabi, Vesna Bumbasierevic, Nicolas Nin, Jose A Lorente, Anders Larsson, Lise Piquilloud, Fekri Abroug, Daniel F McAuley, Lia McNamee, Javier Hurtado, Ed Bajwa, Gabriel Démpaire, Hektor Sula, Lordian Nunci, Alma Cani, Alan Zazu, Christian Dellera, Carolina S Insaurralde, Risso V Alejandro, Julio Daldin, Mauricio Vinzio, Ruben O Fernandez, Luis P Cardonnet, Lisandro R Bettini, Mariano Carboni Bisso, Emilio M Osman, Mariano G Setten, Pablo Lovazzano, Javier Alvarez, Veronica Villar, Norberto C Pozo, Nicolas Grubissich, Gustavo A Plotnikow, Daniela N Vasquez, Santiago Ilutovich, Norberto Tiribelli, Ariel Chena, Carlos A Pellegrini, María G Saenz, Elisa Estenssoro, Matias Brizuela, Hernan Gianinetto, Pablo E Gomez, Valeria I Cerrato, Marco G Bezzi, Silvina A Borello, Flavia A Loiacono, Adriana M Fernandez, Serena Knowles, Claire Reynolds, Deborah M Inskip, Jennene J Miller, Jing Kong, Christina Whitehead, Shailesh Bihari, Aylin Seven, Amanda Krstevski, Helen J 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I Silesky Jimenez, Manuel A González Rojas, Jaime E SolisQuesada, Christian M Ramirez-Alfaro, Jan Máca, Peter Sklienka, Jakob Gjedsted, Aage Christiansen, Jonas Nielsen, Boris G Villamagua, Iguel Llano, Philippe Burtin, Gautier Buzancais, Pascal Beuret, Nicolas Pelletier, Satar Mortaza, Alain Mercat, Jonathan Chelly, Sébastien Jochmans, Nicolas Terzi, Cédric Daubin, Guillaume Carteaux, Nicolas de Prost, Jean-Daniel Chiche, Fabrice Daviaud, Tài Pham, Muriel Fartoukh, Guillaume Barberet, Jerome Biehler, Jean Dellamonica, Denis Doyen, Jean-Michel Arnal, Anais Briquet, Sami Hraiech, Laurent Papazian, Arnaud Follin, Damien Roux, Jonathan Messika, Evangelos Kalaitzis, Laurence Dangers, Alain Combes, Siu-Ming Au, Gaetan Béduneau, Dorothée Carpentier, Elie H Zogheib, Herve Dupont, Sylvie Ricome, Francesco L Santoli, Sebastien L Besset, Philippe Michel, Bruno Gelée, Pierre-Eric Danin, Bernard Goubaux, Philippe J Crova, Nga T Phan, Frantz Berkelmans, Julio C Badie, Romain Tapponnier, Josette 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Paolo Casalena, Sergio Scafetti, Giovanna Panarello, Giovanna Occhipinti, Nicolò Patroniti, Matteo Pozzi, Roberto R Biscione, Michela M Poli, Ferdinando Raimondi, Daniela Albiero, Giulia Crapelli, Eduardo Beck, Vincenzo Pota, Vincenzo Schiavone, Alexandre Molin, Fabio Tarantino, Giacomo Monti, Elena Frati, Lucia Mirabella, Gilda Cinnella, Tommaso Fossali, Riccardo Colombo, Pierpaolo Terragni, Ilaria Pattarino, Francesco Mojoli, Antonio Braschi, Erika E Borotto, Andrea N Cracchiolo, Daniela M Palma, Francesco Raponi, Giuseppe Foti, Ettore R Vascotto, Andrea Coppadoro, Luca Brazzi, Leda Floris, Giorgio A Iotti, Aaron Venti, Osamu Yamaguchi, Shunsuke Takagi, Hiroki N Maeyama, Eizo Watanabe, Yoshihiro Yamaji, Kazuyoshi Shimizu, Kyoko Shiozaki, Satoru Futami, Sekine Ryosuke, Koji Saito, Yoshinobu Kameyama, Keiko Ueno, Masayo Izawa, Nao Okuda, Hiroyuki Suzuki, Tomofumi Harasawa, Michitaka Nasu, Tadaaki Takada, Fumihito Ito, Shin Nunomiya, Kansuke Koyama, Toshikazu Abe, Kohkichi Andoh, Kohei Kusumoto, Akira Hirata, Akihiro Takaba, Hiroyasu Kimura, Shuhei Matsumoto, Ushio Higashijima, Hiroyuki Honda, Nobumasa Aoki, Hiroshi Imai, Yasuaki Ogino, Ichiko Mizuguchi, Kazuya Ichikado, Kenichi Nitta, Katsunori Mochizuki, Tomoaki Hashida, Hiroyuki Tanaka, Tomoyuki Nakamura, Daisuke Niimi, Takeshi Ueda, Yozo Kashiwa, Akinori Uchiyama, Olegs Sabelnikovs, Peteris Oss, Youssef Haddad, Kong Y Liew, Silvio A Ñamendys-Silva, Yves D Jarquin-Badiola, Luis A Sanchez-Hurtado, Saira S Gomez-Flores, Maria C Marin, Asisclo J Villagomez, Jordana S Lemus, Jonathan M Fierro, Mavy Ramirez Cervantes, Francisco Javier Flores Mejia, Dulce Dector, Alejandro Rojas, Daniel R Gonzalez, Claudia R Estrella, Jorge R Sanchez-Medina, Alvaro Ramirez-Gutierrez, Fernando G George, Janet S Aguirre, Juan A Buensuseso, Manuel Poblano, Juan A Buensuseso, Manuel Poblano, Tarek Dendane, Amine Ali Zeggwagh, Hicham Balkhi, Mina Elkhayari, Nacer Samkaoui, Hanane Ezzouine, Abdellatif Benslama, Mourad Amor, Wajdi Maazouzi, Nedim Cimic, Oliver Beck, Monique M Bruns, Jeroen A Schouten, Myra Rinia, Monique Raaijmakers, Leo M Heunks, Hellen M van Wezel, Serge J Heines, Ulrich Strauch, Marc P Buise, Fabienne D Simonis, Marcus J Schultz, Jennifer C Goodson, Troy S Browne, Leanlove Navarra, Anna Hunt, Robyn A Hutchison, Mathew B Bailey, Lynette Newby, Colin McArthur, Michael Kalkoff, Alex Mcleod, Jonathan Casement, Danielle J Hacking, Finn H Andersen, Merete S Dolva, Jon H Laake, Andreas Barratt-Due, Kim Andre L Noremark, Eldar Søreide, Brit Å Sjøbø, Anne B Guttormsen, Hector H Leon Yoshido, Ronald Zumaran Aguilar, Fredy A Montes Oscanoa, Alain U Alisasis, Joanne B Robles, Rossini Abbie B Pasanting-Lim, Beatriz C Tan, Pawel Andruszkiewicz, Karina Jakubowska, Cristina M Coxo, António M Alvarez, Bruno S Oliveira, Gustavo M Montanha, Nelson C Barros, Carlos S Pereira, António M Messias, Jorge M Monteiro, Ana M Araujo, Nuno T Catorze, Susan M Marum, Maria J Bouw, Rui M Gomes, Vania A Brito, Silvia Castro, Joana M Estilita, Filipa M Barros, Isabel M Serra, Aurelia M Martinho, Dana R Tomescu, Alexandra Marcu, Ovidiu H Bedreag, Marius Papurica, Dan E Corneci, Silvius Ioan Negoita, Evgeny Grigoriev, Alexey I Gritsan, Andrey A Gazenkampf, Ghaleb Almekhlafi, Mohamad M Albarrak, Ghanem M Mustafa, Khalid A Maghrabi, Nawal Salahuddin, Tharwat M Aisa, Ahmed S Al Jabbary, Edgardo Tabhan, Yaseen M Arabi, Yaseen M Arabi, Olivia A Trinidad, Hasan M Al Dorzi, Edgardo E Tabhan, Vesna Bumbasirevic, Bojan Jovanovic, Stefan Bolon, Oliver Smith, Jordi Mancebo, Hernan Aguirre-Bermeo, Juan C Lopez-Delgado, Francisco Esteve, Gemma Rialp, Catalina Forteza, Candelaria De Haro, Antonio Artigas, Guillermo M Albaiceta, Sara De Cima-Iglesias, Leticia Seoane-Quiroga, Alexandra Ceniceros-Barros, Antonio L RuizAguilar, Luis M Claraco-Vega, Juan Alfonso Soler, Maria Del Carmen Lorente, Cecilia Hermosa, Federico Gordo, Miryam PrietoGonzález, Juan B López-Messa, Manuel P Perez, Cesar P Perez, Raquel Montoiro Allue, Ferran RocheCampo, Marcos Ibañez-Santacruz, Susana TempranoSusana, Maria C Pintado, Raul De Pablo, Pilar Ricart Aroa Gómez, Silvia Rodriguez Ruiz, Silvia Iglesias Moles, Mª Teresa Jurado, Alfons Arizmendi, Enrique A Piacentini, Nieves Franco, Teresa Honrubia, Meisy Perez Cheng, Elena Perez Losada, Javier Blanco, Luis J Yuste, Cecilia Carbayo-Gorriz, Francisca G Cazorla-Barranquero, Javier G Alonso, Rosa S Alda, Ángela Algaba, Gonzalo Navarro, Enrique Cereijo, Esther Diaz-Rodriguez, Diego Pastor Marcos, Laura Alvarez Montero, Luis Herrera Para, Roberto Jimenez Sanchez, Miguel Angel Blasco Navalpotro, Ricardo Diaz Abad, Raquel Montiel González, Dácil Parrilla Toribio, Alejandro G Castro, Maria Jose D Artiga, Oscar Penuelas, Tomas P Roser, Moreno F Olga, Elena Gallego Curto, Rocío Manzano Sánchez, Vallverdu P Imma, Garcia M Elisabet, Laura Claverias, Monica Magret, Ana M Pellicer, Lucia L Rodriguez, Jesús Sánchez-Ballesteros, Ángela González-Salamanca, Antonio G Jimenez, Francisco P Huerta, Juan Carlos J Sotillo Diaz, Esther Bermejo Lopez, David D Llinares Moya, Alec A Tallet Alfonso, Palazon Sanchez Eugenio Luis, Palazon Sanchez Cesar, Sánchez I Rafael, Corcoles G Virgilio, Noelia N Recio, Christian C Rylander, Bernhard Holzgraefe, Lars M Broman, Joanna Wessbergh, Linnea Persson, Fredrik Schiöler, Hans Kedelv, Anna Oscarsson Tibblin, Henrik Appelberg, Lars Hedlund, Johan Helleberg, Karin E Eriksson, Rita Glietsch, Niklas Larsson, Ingela Nygren, Silvia L Nunes, Anna-Karin Morin, Thomas Kander, Anne Adolfsson, Lise Piquilloud, Hervé O Zender, Corinne Leemann-Refondini, Souheil Elatrous, Slaheddine Bouchoucha, Imed Chouchene, Islem Ouanes, Asma Ben Souissi, Salma Kamoun, Oktay Demirkiran, Mustafa Aker, Emre Erbabacan, Ilkay Ceylan, Nermin Kelebek Girgin, Menekse Ozcelik, Necmettin Ünal, Basak Ceyda Meco, Onat O Akyol, Suleyman S Derman, Barry Kennedy, Ken Parhar, Latha Srinivasa, Lia McNamee, Danny McAuley, Phil Hopkins, Clare Mellis, Vivek Kakar, Dan Hadfield, Andre Vercueil, Kaushik Bhowmick, Sally K Humphreys, Andrew Ferguson, Raymond Mckee, Ashok S Raj, Danielle A Fawkes, Philip Watt, Linda Twohey, Rajeev R Jha, Matthew Thomas, Alex Morton, Varsha Kadaba, Mark J Smith, Anil P Hormis, Santhana G Kannan, Miriam Namih, Henrik Reschreiter, Julie Camsooksai, Alek Kumar, Szabolcs Rugonfalvi, Christopher Nutt, Orla Oneill, Colette Seasman, Ged Dempsey, Christopher J Scott, Helen E Ellis, Stuart Mckechnie, Paula J Hutton, Nora N Di Tomasso, Michela N Vitale, Ruth O Griffin, Michael N Dean, Julius H Cranshaw, Emma L Willett, Nicholas Ioannou, Sarah Gillis, Peter Csabi, Rosaleen Macfadyen, Heidi Dawson, Pieter D Preez, Alexandra J Williams, Owen Boyd, Laura Ortiz-Ruiz de Gordoa, Jon Bramall, Sophie Symmonds, Simon K Chau, Tim Wenham, Tamas Szakmany, Piroska Toth-Tarsoly, Katie H McCalman, Peter Alexander, Lorraine Stephenson, Thomas Collyer, Rhiannon Chapman, Raphael Cooper, Russell M Allan, Malcolm Sim, David W Wrathall, Donald A Irvine, Kim S Zantua, John C Adams, Andrew J Burtenshaw, Gareth P Sellors, Ingeborg D Welters, Karen E Williams, Robert J Hessell, Matthew G Oldroyd, Ceri E Battle, Suresh Pillai, Istvan Kajtor, Mageswaran Sivashanmugavel, Sinead C Okane, Adrian Donnelly, Aniko D Frigyik, Jon P Careless, Martin M May, Richard Stewart, T John Trinder, Samantha J Hagan, Jade M Cole, Caroline C MacFie, Anna T Dowling, Javier Hurtado, Nicolás Nin, Javier Hurtado, Edgardo Nuñez, Gustavo Pittini, Ruben Rodriguez, María C Imperio, Cristina Santos, Ana G França, Alejandro Ebeid, Alberto Deicas, Carolina Serra, Aditya Uppalapati, Ghassan Kamel, Valerie M Banner-Goodspeed, Jeremy R Beitler, Satyanarayana Reddy Mukkera, Shreedhar Kulkarni, John O Shinn Iii, Dina Gomaa, Christopher Tainter, Jarone Lee, Tomaz MesarJarone Lee, Dale J Yeatts, Jessica Warren, Michael J Lanspa, Russel R Miller, Colin K Grissom, Samuel M Brown, Philippe R Bauer, Ryan J Gosselin, Barrett T Kitch, Jason E Cohen, Scott H Beegle, Shazia Choudry, Renaud M Gueret, Aiman Tulaimat, William Stigler, Hitesh Batra, Nidhi G Huff, Keith D Lamb, Trevor W Oetting, Nicholas M Mohr, Claine Judy, Shigeki Saito, Fayez M Kheir, Fayez Kheir, Adam B Schlichting, Angela Delsing, Daniel R Crouch, Mary Elmasri, Daniel R Crouch, Dina Ismail, Kyle R Dreyer, Thomas C Blakeman, Dina Gomaa, Rebecca M Baro, Carolina Quintana Grijalba, Peter C Hou, Raghu Seethala, Imo Aisiku, Galen Henderson, Gyorgy Frendl, Sen-Kuang Hou, Robert L Owens, Ashley Schomer, UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, UCL - (MGD) Services des soins intensifs, and UCL - (SLuc) Service de soins intensifs
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Pulmonary and Respiratory Medicine ,ARDS ,Unidades de cuidados intensivos ,[SDV]Life Sciences [q-bio] ,medicine.medical_treatment ,mechanical ventilation ,NO ,law.invention ,03 medical and health sciences ,Tratamiento médico ,0302 clinical medicine ,law ,Settore MED/41 - ANESTESIOLOGIA ,Insuficiencia respiratoria ,Medicine ,Humans ,030212 general & internal medicine ,Prospective Studies ,Prospective cohort study ,Lung ,Mechanical ventilation ,Respiratory Distress Syndrome ,business.industry ,Respiration ,Incidence (epidemiology) ,medicine.disease ,Intensive care unit ,Respiration, Artificial ,3. Good health ,Intensive Care Units ,lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4] ,medicine.anatomical_structure ,030228 respiratory system ,Respiratory failure ,Heart failure ,Anesthesia ,Artificial ,ards ,business ,Respiratory Insufficiency ,Enfermedad - Abstract
BackgroundCurrent incidence and outcome of patients with acute hypoxaemic respiratory failure requiring mechanical ventilation in the intensive care unit (ICU) are unknown, especially for patients not meeting criteria for acute respiratory distress syndrome (ARDS).MethodsAn international, multicentre, prospective cohort study of patients presenting with hypoxaemia early in the course of mechanical ventilation, conducted during four consecutive weeks in the winter of 2014 in 459 ICUs from 50 countries (LUNG SAFE). Patients were enrolled with arterial oxygen tension/inspiratory oxygen fraction ratio ≤300 mmHg, new pulmonary infiltrates and need for mechanical ventilation with a positive end-expiratory pressure of ≥5 cmH2O. ICU prevalence, causes of hypoxaemia, hospital survival and factors associated with hospital mortality were measured. Patients with unilateral versus bilateral opacities were compared.Findings12 906 critically ill patients received mechanical ventilation and 34.9% with hypoxaemia and new infiltrates were enrolled, separated into ARDS (69.0%), unilateral infiltrate (22.7%) and congestive heart failure (CHF; 8.2%). The global hospital mortality was 38.6%. CHF patients had a mortality comparable to ARDS (44.1% versus 40.4%). Patients with unilateral-infiltrate had lower unadjusted mortality, but similar adjusted mortality compared to those with ARDS. The number of quadrants on chest imaging was associated with an increased risk of death. There was no difference in mortality comparing patients with unilateral-infiltrate and ARDS with only two quadrants involved.InterpretationMore than one-third of patients receiving mechanical ventilation have hypoxaemia and new infiltrates with a hospital mortality of 38.6%. Survival is dependent on the degree of pulmonary involvement whether or not ARDS criteria are reached.
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- 2021
3. Mesenchymal stem/stromal cells stably transduced with an inhibitor of CC chemokine ligand 2 ameliorate bronchopulmonary dysplasia and pulmonary hypertension
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Toshihiko Suzuki, Atsuto Onoda, Hidenori Yamamoto, Masahiro Hayakawa, Yuma Kitase, Takayuki Nakayama, Yoshiyuki Takahashi, Yuichiro Sugiyama, Shigeki Saito, Taichi Kato, Yoshiaki Sato, Kazuto Ueda, and Haruka Mimatsu
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Male ,0301 basic medicine ,Cancer Research ,Stromal cell ,Receptors, CCR2 ,Hypertension, Pulmonary ,Immunology ,Vascular Remodeling ,CCL2 ,Lung injury ,Mesenchymal Stem Cell Transplantation ,Transfection ,Viral vector ,03 medical and health sciences ,0302 clinical medicine ,Transduction, Genetic ,mental disorders ,Animals ,Humans ,Immunology and Allergy ,Medicine ,Macrophage ,Rats, Wistar ,Chemokine CCL2 ,Genetics (clinical) ,Bronchopulmonary Dysplasia ,Transplantation ,business.industry ,Macrophages ,Mesenchymal stem cell ,Cell Biology ,Macrophage Activation ,medicine.disease ,Pulmonary hypertension ,Rats ,Disease Models, Animal ,HEK293 Cells ,030104 developmental biology ,Oncology ,Bronchopulmonary dysplasia ,030220 oncology & carcinogenesis ,Cancer research ,Female ,Mutant Proteins ,business - Abstract
Perinatal bronchopulmonary dysplasia (BPD) is defined as lung injury in preterm infants caused by various factors, resulting in serious respiratory dysfunction and high mortality. The administration of mesenchymal stem/stromal cells (MSCs) to treat/prevent BPD has proven to have certain therapeutic effects. However, MSCs can only weakly regulate macrophage function, which is strongly involved in the development of BPD. 7ND-MSCs are MSCs transfected with 7ND, a truncated version of CC chemokine ligand 2 (CCL2) that promotes macrophage activation, using a lentiviral vector. In the present study, we show in a BPD rat model that 7ND-MSC administration, but not MSCs alone, ameliorated the impaired alveolarization evaluated by volume density and surface area in the lung tissue, as well as pulmonary artery remodeling and pulmonary hypertension induced by BPD. In addition, 7ND-MSCs, but not MSCs alone, reduced M1 macrophages and the messenger RNA expressions of interleukin-6 and CCL2 in the lung tissue. Thus, the present study showed the treatment effect of 7ND-MSCs in a BPD rat model, which was more effective than that of MSCs alone.
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- 2020
4. Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome: Insights from the LUNG SAFE study
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Madotto F, Rezoagli E, Pham T, Schmidt M, McNicholas B, Protti A, Panwar R, Bellani G, Fan E, van Haren F, Brochard L, Laffey JG, Antonio Pesenti, John G Laffey, Laurent Brochard, Andres Esteban, Luciano Gattinoni, Frank van Haren, Anders Larsson, Daniel F McAuley, Marco Ranieri, Gordon Rubenfeld, B Taylor Thompson, Hermann Wrigge, Arthur S Slutsky, Fernando Rios, T Sottiaux, P Depuydt, Fredy S Lora, Luciano Cesar Azevedo, Eddy Fan, Guillermo Bugedo, Haibo Qiu, Marcos Gonzalez, Juan Silesky, Vladimir Cerny, Jonas Nielsen, Manuel Jibaja, Tài Pham, Dimitrios Matamis, Jorge Luis Ranero, Pravin Amin, S M Hashemian, Kevin Clarkson, Giacomo Bellani, Kiyoyasu Kurahashi, Asisclo Villagomez, Amine Ali Zeggwagh, Leo M Heunks, Jon Henrik Laake, Jose Emmanuel Palo, Antero do Vale Fernandes, Dorel Sandesc, Yaasen Arabi, Vesna Bumbasierevic, Nicolas Nin, Jose A Lorente, Lise Piquilloud, Fekri Abroug, Lia McNamee, Javier Hurtado, Ed Bajwa, Gabriel Démpaire, Uhc Mother Theresa, Hektor Sula, Lordian Nunci, Alma Cani, Villa Maria, Alan Zazu, Christian Dellera, Carolina S Insaurralde, Risso V Alejandro, Julio Daldin, Mauricio Vinzio, Ruben O Fernandez, Luis P Cardonnet, Lisandro R Bettini, Mariano Carboni Bisso, Emilio M Osman, Mariano G Setten, Pablo Lovazzano, Javier Alvarez, Veronica Villar, Norberto C Pozo, Nicolas Grubissich, Gustavo A Plotnikow, Daniela N Vasquez, Santiago Ilutovich, Norberto Tiribelli, Ariel Chena, Carlos A Pellegrini, María G Saenz, Elisa Estenssoro, Matias Brizuela, Hernan Gianinetto, Pablo E Gomez, Valeria I Cerrato, Marco G Bezzi, Silvina A Borello, Flavia A Loiacono, Adriana M Fernandez, Serena Knowles, Claire Reynolds, Deborah M Inskip, Jennene J Miller, Jing Kong, Christina Whitehead, Shailesh Bihari, Aylin Seven, Amanda Krstevski, Helen J Rodgers, Rebecca T Millar, Toni E Mckenna, Irene M Bailey, Gabrielle C Hanlon, Anders Aneman, Joan M Lynch, Raman Azad, John Neal, Paul W Woods, Brigit L Roberts, Mark R Kol, Helen S Wong, Katharina C Riss, Thomas Staudinger, Xavier Wittebole, Caroline Berghe, Pierre A Bulpa, Alain M Dive, Rik Verstraete, Herve Lebbinck, Pieter Depuydt, Joris Vermassen, Philippe Meersseman, Helga Ceunen, Jonas I Rosa, Daniel O Beraldo, Claudio Piras, Adenilton M Rampinelli, Antonio P Nassar Jr, Sergio Mataloun, Marcelo Moock, Marlus M Thompson, Claudio H Gonçalves, Ana Carolina P Antônio, Aline Ascoli, Rodrigo S Biondi, Danielle C Fontenele, Danielle Nobrega, Vanessa M Sales, Suresh Shindhe, Dk Maizatul Aiman B Pg Hj Ismail, John Laffey, Francois Beloncle, Kyle G Davies, Rob Cirone, Venika Manoharan, Mehvish Ismail, Ewan C Goligher, Mandeep Jassal, Erin Nishikawa, Areej Javeed, Gerard Curley, Nuttapol Rittayamai, Matteo Parotto, Niall D Ferguson, Sangeeta Mehta, Jenny Knoll, Antoine Pronovost, Sergio Canestrini, Alejandro R Bruhn, Patricio H Garcia, Felipe A Aliaga, Pamela A Farías, Jacob S Yumha, Claudia A Ortiz, Javier E Salas, Alejandro A Saez, Luis D Vega, Eduardo F Labarca, Felipe T Martinez, Nicolás G Carreño, Pilar Lora, Haitao Liu, Ling Liu, Rui Tang, Xiaoming Luo, Youzhong An, Huiying Zhao, Yan Gao, Zhe Zhai, Zheng L Ye, Wei Wang, Wenwen Li, Qingdong Li, Ruiqiang Zheng, Wenkui Yu, Juanhong Shen, Xinyu Li, Tao Yu, Weihua Lu, Ya Q Wu, Xiao B Huang, Zhenyang He, Yuanhua Lu, Hui Han, Fan Zhang, Renhua Sun, Hua X Wang, Shu H Qin, Bao H Zhu, Jun Zhao, Jian Liu, Bin Li, Jing L Liu, Fa C Zhou, Qiong J Li, Xing Y Zhang, Zhou Li-Xin, Qiang Xin-Hua, Liangyan Jiang, Yuan N Gao, Xian Y Zhao, Yuan Y Li, Xiao L Li, Chunting Wang, Qingchun Yao, Rongguo Yu, Kai Chen, Huanzhang Shao, Bingyu Qin, Qing Q Huang, Wei H Zhu, Ai Y Hang, Ma X Hua, Yimin Li, Yonghao Xu, Yu D Di, Long L Ling, Tie H Qin, Shou H Wang, Junping Qin, Yi Han, Suming Zhou, Monica P Vargas, Juan I Silesky Jimenez, Manuel A González Rojas, Jaime E Solis-Quesada, Christian M Ramirez-Alfaro, Jan Máca, Peter Sklienka, Jakob Gjedsted, Aage Christiansen, Boris G Villamagua, Miguel Llano, Philippe Burtin, Gautier Buzancais, Pascal Beuret, Nicolas Pelletier, Satar Mortaza, Alain Mercat, Jonathan Chelly, Sébastien Jochmans, Nicolas Terzi, Cédric Daubin, Guillaume Carteaux, Nicolas de Prost, Jean-Daniel Chiche, Fabrice Daviaud, Tai Pham, Muriel Fartoukh, Guillaume Barberet, Jerome Biehler, Jean Dellamonica, Denis Doyen, Jean-Michel Arnal, Anais Briquet, Sami Hraiech, Laurent Papazian, Arnaud Follin, Damien Roux, Jonathan Messika, Evangelos Kalaitzis, Laurence Dangers, Alain Combes, Siu-Ming Au, Gaetan Béduneau, Dorothée Carpentier, Elie H Zogheib, Herve Dupont, Sylvie Ricome, Francesco L Santoli, Sebastien L Besset, Philippe Michel, Bruno Gelée, Pierre-Eric Danin, Bernard Goubaux, Philippe J Crova, Nga T Phan, Frantz Berkelmans, Julio C Badie, Romain Tapponnier, Josette Gally, Samy Khebbeb, Jean-Etienne Herbrecht, Francis Schneider, Pierre-Louis M Declercq, Jean-Philippe Rigaud, Jacques Duranteau, Anatole Harrois, Russell Chabanne, Julien Marin, Charlene Bigot, Sandrine Thibault, Mohammed Ghazi, Messabi Boukhazna, Salem Ould Zein, Jack R Richecoeur, Daniele M Combaux, Fabien Grelon, Charlene Le Moal, Elise P Sauvadet, Adrien Robine, Virginie Lemiale, Danielle Reuter, Martin Dres, Alexandre Demoule, Dany Goldgran-Toledano, Loredana Baboi, Claude Guérin, Ralph Lohner, Jens Kraßler, Susanne Schäfer, Kai D Zacharowski, Patrick Meybohm, Andreas W Reske, Philipp Simon, Hans-Bernd F Hopf, Michael Schuetz, Thomas Baltus, Metaxia N Papanikolaou, Theonymfi G Papavasilopoulou, Giannis A Zacharas, Vasilis Ourailogloy, Eleni K Mouloudi, Eleni V Massa, Eva O Nagy, Electra E Stamou, Ellada V Kiourtzieva, Marina A Oikonomou, Luis E Avila, Cesar A Cortez, Johanna E Citalán, Sameer A Jog, Safal D Sable, Bhagyesh Shah, Mohan Gurjar, Arvind K Baronia, Mohammedfaruk Memon, Radhakrishnan Muthuchellappan, Venkatapura J Ramesh, Anitha Shenoy, Ramesh Unnikrishnan, Subhal B Dixit, Rachana V Rhayakar, Nagarajan Ramakrishnan, Vallish K Bhardwaj, Heera L Mahto, Sudha V Sagar, Vijayanand Palaniswamy, Deeban Ganesan, Seyed Mohammadreza Hashemian, Hamidreza Jamaati, Farshad Heidari, Edel A Meaney, Alistair Nichol, Karl M Knapman, Donall O'Croinin, Eimhin S Dunne, Dorothy M Breen, Kevin P Clarkson, Rola F Jaafar, Rory Dwyer, Fahd Amir, Olaitan O Ajetunmobi, Aogan C O'Muircheartaigh, Colin S Black, Nuala Treanor, Daniel V Collins, Wahid Altaf, Gianluca Zani, Maurizio Fusari, Savino Spadaro, Carlo A Volta, Romano Graziani, Barbara Brunettini, Salvatore Palmese, Paolo Formenti, Michele Umbrello, Andrea Lombardo, Elisabetta Pecci, Marco Botteri, Monica Savioli, Alessandro Protti, Alessia Mattei, Lorenzo Schiavoni, Andrea Tinnirello, Manuel Todeschini, Antonino Giarratano, Andrea Cortegiani, Sara Sher, Anna Rossi, Massimo M Antonelli, Luca M Montini, Paolo Casalena, Sergio Scafetti, Giovanna Panarello, Giovanna Occhipinti, Nicolò Patroniti, Matteo Pozzi, Roberto R Biscione, Michela M Poli, Ferdinando Raimondi, Daniela Albiero, Giulia Crapelli, Eduardo Beck, Vincenzo Pota, Vincenzo Schiavone, Alexandre Molin, Fabio Tarantino, Giacomo Monti, Elena Frati, Lucia Mirabella, Gilda Cinnella, Tommaso Fossali, Riccardo Colombo, Pierpaolo Terragni Ilaria Pattarino, Francesco Mojoli, Antonio Braschi, Erika E Borotto, Andrea N Cracchiolo, Daniela M Palma, Francesco Raponi, Giuseppe Foti, Ettore R Vascotto, Andrea Coppadoro, Luca Brazzi, Leda Floris, Giorgio A Iotti, Aaron Venti, Osamu Yamaguchi, Shunsuke Takagi, Hiroki N Maeyama, Eizo Watanabe, Yoshihiro Yamaji, Kazuyoshi Shimizu, Kyoko Shiozaki, Satoru Futami, Sekine Ryosuke, Koji Saito, Yoshinobu Kameyama, Keiko Ueno, Masayo Izawa, Nao Okuda, Hiroyuki Suzuki, Tomofumi Harasawa, Michitaka Nasu, Tadaaki Takada, Fumihito Ito, Shin-Nunomiya Kansuke-Koyama, Toshikazu Abe, Kohkichi Andoh, Kohei Kusumoto, Akira Hirata, Akihiro Takaba, Hiroyasu Kimura, Shuhei Matsumoto, Ushio Higashijima, Hiroyuki Honda, Nobumasa Aoki, Hiroshi Imai, Yasuaki Ogino, Ichiko Mizuguchi, Kazuya Ichikado, Kenichi Nitta, Katsunori Mochizuki, Tomoaki Hashida, Hiroyuki Tanaka, Tomoyuki Nakamura, Daisuke Niimi, Takeshi Ueda, Yozo Kashiwa, Akinori Uchiyama, Olegs Sabelnikovs, Peteris Oss, Youssef Haddad, Kong Y Liew, Silvio A Ñamendys-Silva, Yves D Jarquin-Badiola, Luis A Sanchez-Hurtado, Saira S Gomez-Flores, Maria C Marin, Asisclo J Villagomez, Jordana S Lemus, Jonathan M Fierro, Mavy Ramirez Cervantes, Francisco Javier Flores Mejia, Dulce Dector, Dulce M Dector, Daniel R Gonzalez, Claudia R Estrella, Jorge R Sanchez-Medina, Alvaro Ramirez-Gutierrez, Fernando G George, Janet S Aguirre, Juan A Buensuseso, Manuel Poblano, Tarek Dendane, Hicham Balkhi, Mina Elkhayari, Nacer Samkaoui, Hanane Ezzouine, Abdellatif Benslama Mourad Amor, Wajdi Maazouzi, Nedim Cimic, Oliver Beck, Monique M Bruns, Jeroen A Schouten, Myra-Rinia, Monique Raaijmakers, Hellen M Van Wezel, Serge J Heines, Ulrich Strauch, Marc P Buise, Fabienne D Simonis, Marcus J Schultz, Jennifer C Goodson, Troy S Browne, Leanlove Navarra, Anna Hunt, Robyn A Hutchison, Mathew B Bailey, Lynette Newby, Colin Mcarthur, Michael Kalkoff, Alex Mcleod, Jonathan Casement, Danielle J Hacking, Finn H Andersen, Merete S Dolva, Jon H Laake, Andreas Barratt-Due, Kim Andre L Noremark, Eldar Søreide, Brit Å Sjøbø, Anne B Guttormsen, Hector H Leon Yoshido, Ronald Zumaran Aguilar, Fredy A Montes Oscanoa, Alain U Alisasis, Joanne B Robles, Rossini Abbie B Pasanting-Lim, Beatriz C Tan, Pawel Andruszkiewicz, Karina Jakubowska, Cristina M Coxo, António M Alvarez, Bruno S Oliveira, Gustavo M Montanha, Nelson C Barros, Carlos S Pereira, António M Messias, Jorge M Monteiro, Ana M Araujo, Nuno T Catorze, Susan M Marum, Maria J Bouw, Rui M Gomes, Vania A Brito, Silvia Castro, Joana M Estilita, Filipa M Barros, Isabel M Serra, Aurelia M Martinho, Dana R Tomescu, Alexandra Marcu, Ovidiu H Bedreag, Marius Papurica, Dan E Corneci, Silvius Ioan Negoita, Evgeny Grigoriev, Alexey I Gritsan, Andrey A Gazenkampf, Ghaleb Almekhlafi, Mohamad M Albarrak, Ghanem M Mustafa, Khalid A Maghrabi, Nawal Salahuddin, Tharwat M 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H., Qin, J., Han, Y., Zhou, S., Vargas, M. P., Silesky Jimenez, J. I., Gonzalez Rojas, M. A., Solis-Quesada, J. E., Ramirez-Alfaro, C. M., Maca, J., Sklienka, P., Gjedsted, J., Christiansen, A., Villamagua, B. G., Llano, M., Burtin, P., Buzancais, G., Beuret, P., Pelletier, N., Mortaza, S., Mercat, A., Chelly, J., Jochmans, S., Terzi, N., Daubin, C., Carteaux, G., De Prost, N., Chiche, J. -D., Daviaud, F., Fartoukh, M., Barberet, G., Biehler, J., Dellamonica, J., Doyen, D., Arnal, J. -M., Briquet, A., Hraiech, S., Papazian, L., Follin, A., Roux, D., Messika, J., Kalaitzis, E., Dangers, L., Combes, A., Au, S. -M., Beduneau, G., Carpentier, D., Zogheib, E. H., Dupont, H., Ricome, S., Santoli, F. L., Besset, S. L., Michel, P., Gelee, B., Danin, P. -E., Goubaux, B., Crova, P. J., Phan, N. T., Berkelmans, F., Badie, J. C., Tapponnier, R., Gally, J., Khebbeb, S., Herbrecht, J. -E., Schneider, F., Declercq, P. -L. M., Rigaud, J. -P., Duranteau, J., Harrois, A., Chabanne, R., Marin, J., Bigot, C., Thibault, S., Ghazi, M., Boukhazna, M., Zein, S. O., Richecoeur, J. R., Combaux, D. M., Grelon, F., Le Moal, C., Sauvadet, E. P., Robine, A., Lemiale, V., Reuter, D., Dres, M., Demoule, A., Goldgran-Toledano, D., Baboi, L., Guerin, C., Lohner, R., Krassler, J., Schafer, S., Zacharowski, K. D., Meybohm, P., Reske, A. W., Simon, P., Hopf, H. -B. F., Schuetz, M., Baltus, T., Papanikolaou, M. N., Papavasilopoulou, T. G., Zacharas, G. A., Ourailogloy, V., Mouloudi, E. K., Massa, E. V., Nagy, E. O., Stamou, E. E., Kiourtzieva, E. V., Oikonomou, M. A., Avila, L. E., Cortez, C. A., Citalan, J. E., Jog, S. A., Sable, S. D., Shah, B., Gurjar, M., Baronia, A. K., Memon, M., Muthuchellappan, R., Ramesh, V. J., Shenoy, A., Unnikrishnan, R., Dixit, S. B., Rhayakar, R. V., Ramakrishnan, N., Bhardwaj, V. K., Mahto, H. L., Sagar, S. V., Palaniswamy, V., Ganesan, D., Jamaati, H., Heidari, F., Meaney, E. 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M., Tulaimat, A., Choudry, S., Stigler, W., Batra, H., Huff, N. G., Lamb, K. D., Oetting, T. W., Mohr, N. M., Judy, C., Saito, S., Kheir, F. M., Kheir, F., Schlichting, A. B., Delsing, A., Crouch, D. R., Elmasri, M., Ismail, D., Dreyer, K. R., Blakeman, T. C., Baron, R. M., Grijalba, C. Q., Hou, P. C., Seethala, R., Aisiku, I., Henderson, G., Frendl, G., Hou, S. -K., Owens, R. L., Schomer, A., Bumbasirevic, V., Jovanovic, B., Surbatovic, M., Veljovic, M., UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, UCL - (MGD) Services des soins intensifs, UCL - (SLuc) Service de soins intensifs, Graduate School, Intensive Care Medicine, ACS - Heart failure & arrhythmias, ACS - Diabetes & metabolism, ACS - Pulmonary hypertension & thrombosis, ACS - Microcirculation, Madotto, F, Rezoagli, E, Pham, T, Schmidt, M, Mcnicholas, B, Protti, A, Panwar, R, Bellani, G, Fan, E, Van Haren, F, Brochard, L, Laffey, J, Pesenti, A, Esteban, A, Gattinoni, L, Larsson, A, Mcauley, D, Ranieri, M, Rubenfeld, G, Thompson, B, Wrigge, H, Slutsky, A, Rios, F, Sottiaux, T, Depuydt, P, Lora, F, Azevedo, L, Bugedo, G, Qiu, H, Gonzalez, M, Silesky, J, Cerny, V, Nielsen, J, Jibaja, M, Matamis, D, Ranero, J, Amin, P, Hashemian, S, Clarkson, K, Kurahashi, K, Villagomez, A, Zeggwagh, A, Heunks, L, Laake, J, Palo, J, Do Vale Fernandes, A, Sandesc, D, Arabi, Y, Bumbasierevic, V, Nin, N, Lorente, J, 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Carlos A Pellegrini, María G Saenz, Elisa Estenssoro, Matias Brizuela, Hernan Gianinetto, Pablo E Gomez, Valeria I Cerrato, Marco G Bezzi, Silvina A Borello, Flavia A Loiacono, Adriana M Fernandez, Serena Knowles, Claire Reynolds, Deborah M Inskip, Jennene J Miller, Jing Kong, Christina Whitehead, Shailesh Bihari, Aylin Seven, Amanda Krstevski, Helen J Rodgers, Rebecca T Millar, Toni E Mckenna, Irene M Bailey, Gabrielle C Hanlon, Anders Aneman, Joan M Lynch, Raman Azad, John Neal, Paul W Woods, Brigit L Roberts, Mark R Kol, Helen S Wong, Katharina C Riss, Thomas Staudinger, Xavier Wittebole, Caroline Berghe, Pierre A Bulpa, Alain M Dive, Rik Verstraete, Herve Lebbinck, Pieter Depuydt, Joris Vermassen, Philippe Meersseman, Helga Ceunen, Jonas I Rosa, Daniel O Beraldo, Claudio Piras, Adenilton M Rampinelli, Antonio P Nassar Jr, Sergio Mataloun, Marcelo Moock, Marlus M Thompson, Claudio H Gonçalves, Ana Carolina P Antônio, Aline Ascoli, Rodrigo S Biondi, Danielle C Fontenele, Danielle 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Papanikolaou, Theonymfi G Papavasilopoulou, Giannis A Zacharas, Vasilis Ourailogloy, Eleni K Mouloudi, Eleni V Massa, Eva O Nagy, Electra E Stamou, Ellada V Kiourtzieva, Marina A Oikonomou, Luis E Avila, Cesar A Cortez, Johanna E Citalán, Sameer A Jog, Safal D Sable, Bhagyesh Shah, Mohan Gurjar, Arvind K Baronia, Mohammedfaruk Memon, Radhakrishnan Muthuchellappan, Venkatapura J Ramesh, Anitha Shenoy, Ramesh Unnikrishnan, Subhal B Dixit, Rachana V Rhayakar, Nagarajan Ramakrishnan, Vallish K Bhardwaj, Heera L Mahto, Sudha V Sagar, Vijayanand Palaniswamy, Deeban Ganesan, Seyed Mohammadreza Hashemian, Hamidreza Jamaati, Farshad Heidari, Edel A Meaney, Alistair Nichol, Karl M Knapman, Donall O'Croinin, Eimhin S Dunne, Dorothy M Breen, Kevin P Clarkson, Rola F Jaafar, Rory Dwyer, Fahd Amir, Olaitan O Ajetunmobi, Aogan C O'Muircheartaigh, Colin S Black, Nuala Treanor, Daniel V Collins, Wahid Altaf, Gianluca Zani, Maurizio Fusari, Savino Spadaro, Carlo A Volta, Romano Graziani, Barbara Brunettini, Salvatore Palmese, Paolo Formenti, Michele Umbrello, Andrea Lombardo, Elisabetta Pecci, Marco Botteri, Monica Savioli, Alessandro Protti, Alessia Mattei, Lorenzo Schiavoni, Andrea Tinnirello, Manuel Todeschini, Antonino Giarratano, Andrea Cortegiani, Sara Sher, Anna Rossi, Massimo M Antonelli, Luca M Montini, Paolo Casalena, Sergio Scafetti, Giovanna Panarello, Giovanna Occhipinti, Nicolò Patroniti, Matteo Pozzi, Roberto R Biscione, Michela M Poli, Ferdinando Raimondi, Daniela Albiero, Giulia Crapelli, Eduardo Beck, Vincenzo Pota, Vincenzo Schiavone, Alexandre Molin, Fabio Tarantino, Giacomo Monti, Elena Frati, Lucia Mirabella, Gilda Cinnella, Tommaso Fossali, Riccardo Colombo, Pierpaolo Terragni Ilaria Pattarino, Francesco Mojoli, Antonio Braschi, Erika E Borotto, Andrea N Cracchiolo, Daniela M Palma, Francesco Raponi, Giuseppe Foti, Ettore R Vascotto, Andrea Coppadoro, Luca Brazzi, Leda Floris, Giorgio A Iotti, Aaron Venti, Osamu Yamaguchi, Shunsuke Takagi, Hiroki N Maeyama, Eizo Watanabe, Yoshihiro Yamaji, Kazuyoshi Shimizu, Kyoko Shiozaki, Satoru Futami, Sekine Ryosuke, Koji Saito, Yoshinobu Kameyama, Keiko Ueno, Masayo Izawa, Nao Okuda, Hiroyuki Suzuki, Tomofumi Harasawa, Michitaka Nasu, Tadaaki Takada, Fumihito Ito, Shin-Nunomiya, Kansuke-Koyama, Toshikazu Abe, Kohkichi Andoh, Kohei Kusumoto, Akira Hirata, Akihiro Takaba, Hiroyasu Kimura, Shuhei Matsumoto, Ushio Higashijima, Hiroyuki Honda, Nobumasa Aoki, Hiroshi Imai, Yasuaki Ogino, Ichiko Mizuguchi, Kazuya Ichikado, Kenichi Nitta, Katsunori Mochizuki, Tomoaki Hashida, Hiroyuki Tanaka, Tomoyuki Nakamura, Daisuke Niimi, Takeshi Ueda, Yozo Kashiwa, Akinori Uchiyama, Olegs Sabelnikovs, Peteris Oss, Youssef Haddad, Kong Y Liew, Silvio A Ñamendys-Silva, Yves D Jarquin-Badiola, Luis A Sanchez-Hurtado, Saira S Gomez-Flores, Maria C Marin, Asisclo J Villagomez, Jordana S Lemus, Jonathan M Fierro, Mavy Ramirez Cervantes, Francisco Javier Flores Mejia, Dulce Dector, Dulce M Dector, Daniel R Gonzalez, Claudia R Estrella, Jorge R Sanchez-Medina, Alvaro Ramirez-Gutierrez, Fernando G George, Janet S Aguirre, Juan A Buensuseso, Manuel Poblano, Tarek Dendane, Hicham Balkhi, Mina Elkhayari, Nacer Samkaoui, Hanane Ezzouine, Abdellatif Benslama Mourad Amor, Wajdi Maazouzi, Nedim Cimic, Oliver Beck, Monique M Bruns, Jeroen A Schouten, Myra-Rinia, Monique Raaijmakers, Hellen M Van Wezel, Serge J Heines, Ulrich Strauch, Marc P Buise, Fabienne D Simonis, Marcus J Schultz, Jennifer C Goodson, Troy S Browne, Leanlove Navarra, Anna Hunt, Robyn A Hutchison, Mathew B Bailey, Lynette Newby, Colin Mcarthur, Michael Kalkoff, Alex Mcleod, Jonathan Casement, Danielle J Hacking, Finn H Andersen, Merete S Dolva, Jon H Laake, Andreas Barratt-Due, Kim Andre L Noremark, Eldar Søreide, Brit Å Sjøbø, Anne B Guttormsen, Hector H Leon Yoshido, Ronald Zumaran Aguilar, Fredy A Montes Oscanoa, Alain U Alisasis, Joanne B Robles, Rossini Abbie B Pasanting-Lim, Beatriz C Tan, Pawel Andruszkiewicz, Karina Jakubowska, Cristina M Coxo, António M Alvarez, Bruno S Oliveira, Gustavo M Montanha, Nelson C Barros, Carlos S Pereira, António M Messias, Jorge M Monteiro, Ana M Araujo, Nuno T Catorze, Susan M Marum, Maria J Bouw, Rui M Gomes, Vania A Brito, Silvia Castro, Joana M Estilita, Filipa M Barros, Isabel M Serra, Aurelia M Martinho, Dana R Tomescu, Alexandra Marcu, Ovidiu H Bedreag, Marius Papurica, Dan E Corneci, Silvius Ioan Negoita, Evgeny Grigoriev, Alexey I Gritsan, Andrey A Gazenkampf, Ghaleb Almekhlafi, Mohamad M Albarrak, Ghanem M Mustafa, Khalid A Maghrabi, Nawal Salahuddin, Tharwat M Aisa, Ahmed S Al Jabbary, Edgardo Tabhan, Yaseen M Arabi, Olivia A Trinidad, Hasan M Al Dorzi, Edgardo E Tabhan, Stefan Bolon, Oliver Smith, Jordi Mancebo, Hernan Aguirre-Bermeo, Juan C Lopez-Delgado, Francisco Esteve, Gemma Rialp, Catalina Forteza, Candelaria De Haro, Antonio Artigas, Guillermo M Albaiceta, Sara De Cima-Iglesias, Leticia Seoane-Quiroga, Alexandra Ceniceros-Barros, Antonio L Ruiz-Aguilar, Luis M Claraco-Vega, Juan Alfonso Soler, Maria Del Carmen Lorente, Cecilia Hermosa, Federico Gordo, Miryam-Prieto-González, Juan B López-Messa, Manuel P Perez, Cesar P Perez, Raquel Montoiro Allue, Ferran Roche-Campo, Marcos Ibañez-Santacruz, Susana-Temprano, Maria C Pintado, Raul De Pablo, Pilar Ricart Aroa Gómez, Silvia Rodriguez Ruiz, Silvia Iglesias Moles, Mª Teresa Jurado, Alfons Arizmendi, Enrique A Piacentini, Nieves Franco, Teresa Honrubia, Meisy Perez Cheng, Elena Perez Losada, Javier-Blanco, Luis J Yuste, Cecilia Carbayo-Gorriz, Francisca G Cazorla-Barranquero, Javier G Alonso, Rosa S Alda, Ángela Algaba, Gonzalo Navarro, Enrique Cereijo, Esther Diaz-Rodriguez, Diego Pastor Marcos, Laura Alvarez Montero, Luis Herrera Para, Roberto Jimenez Sanchez, Miguel Angel Blasco Navalpotro, Ricardo Diaz Abad, Raquel Montiel Gonz Á Lez, D Á Cil Parrilla Toribio, Alejandro G Castro, Maria Jose D Artiga, Oscar Penuelas, Tomas P Roser, Moreno F Olga, Elena Gallego Curto, Rocío Manzano Sánchez, Vallverdu P Imma, Garcia M Elisabet, Laura Claverias, Monica Magret, Ana M Pellicer, Lucia L Rodriguez, Jesús Sánchez-Ballesteros, Ángela González-Salamanca, Antonio G Jimenez, Francisco P Huerta, Juan Carlos J Sotillo Diaz, Esther Bermejo Lopez, David D Llinares Moya, Alec A Tallet Alfonso, Palazon Sanchez Eugenio Luis, Palazon Sanchez Cesar, Sánchez I Rafael, Corcoles G Virgilio, Noelia N Recio, Richard O Adamsson, Christian C Rylander, Bernhard Holzgraefe, Lars M Broman, Joanna Wessbergh, Linnea Persson, Fredrik Schiöler, Hans Kedelv, Anna Oscarsson Tibblin, Henrik Appelberg, Lars Hedlund, Johan Helleberg, Karin E Eriksson, Rita Glietsch, Niklas Larsson, Ingela Nygren, Silvia L Nunes, Anna-Karin Morin, Thomas Kander, Anne Adolfsson, Hervé O Zender, Corinne Leemann-Refondini, Souheil Elatrous, Slaheddine Bouchoucha, Imed Chouchene, Islem Ouanes, Asma Ben Souissi, Salma Kamoun, Oktay Demirkiran, Mustafa Aker, Emre Erbabacan, Ilkay Ceylan, Nermin Kelebek Girgin, Menekse Ozcelik, Necmettin Ünal, Basak Ceyda Meco, Onat O Akyol, Suleyman S Derman, Barry Kennedy, Ken Parhar, Latha Srinivasa, Danny McAuley, Phil Hopkins, Clare Mellis, Vivek Kakar, Dan Hadfield, Andre Vercueil, Kaushik Bhowmick, Sally K Humphreys, Andrew Ferguson, Raymond Mckee, Ashok S Raj, Danielle A Fawkes, Philip Watt, Linda Twohey, Rajeev R JhaMatthew Thomas, Alex Morton, Varsha Kadaba, Mark J Smith, Anil P Hormis, Santhana G Kannan, Miriam Namih, Henrik Reschreiter, Julie Camsooksai, Alek Kumar, Szabolcs Rugonfalvi, Christopher Nutt, Orla O'Neill, Colette Seasman, Ged Dempsey, Christopher J Scott, Helen E Ellis, Stuart Mckechnie, Paula J Hutton, Nora N Di Tomasso, Michela N Vitale, Ruth O Griffin, Michael N Dean, Julius H Cranshaw, Emma L Willett, Nicholas Ioannou, Sarah Gillis, Peter Csabi, Rosaleen Macfadyen, Heidi Dawson, Pieter D Preez, Alexandra J Williams, Owen Boyd, Laura Ortiz-Ruiz De Gordoa, Jon Bramall, Sophie Symmonds, Simon K Chau, Tim Wenham, Tamas Szakmany, Piroska Toth-Tarsoly, Katie H McCalman, Peter Alexander, Lorraine Stephenson, Thomas Collyer, Rhiannon Chapman, Raphael Cooper, Russell M Allan, Malcolm Sim, David W Wrathall, Donald A Irvine, Kim S Zantua, John C Adams, Andrew J Burtenshaw, Gareth P Sellors, Ingeborg D Welters, Karen E Williams, Robert J Hessell, Matthew G Oldroyd, Ceri E Battle, Suresh Pillai, Istvan Kajtor, Mageswaran Sivashanmugavel, Sinead C O'Kane, Adrian Donnelly, Aniko D Frigyik, Jon P Careless, Martin M May, Richard Stewart, T John Trinder, Samantha J Hagan, Matt P Wise, Jade M Cole, Caroline C MacFie, Anna T Dowling, Nicolás Nin, Edgardo Nuñez, Gustavo Pittini, Ruben Rodriguez, María C Imperio, Cristina Santos, Ana G França, Alejandro Ebeid, Alberto Deicas, Carolina Serra, Aditya Uppalapati, Ghassan Kamel, Valerie M Banner-Goodspeed, Jeremy R Beitler, Satyanarayana Reddy Mukkera, Shreedhar Kulkarni, Jarone Lee, Tomaz Mesar, John O Shinn 3rd, Dina Gomaa, Christopher Tainter, Dale J Yeatts, Jessica Warren, Michael J Lanspa, Russel R Miller, Colin K Grissom, Madotto F, Rezoagli E, Pham T, Schmidt M, McNicholas B, Protti A, Panwar R, Bellani G, Fan E, van Haren F, Brochard L, Laffey JG, and LUNG SAFE Investigators and the ESICM Trials Group, Samuel M Brown, Philippe R Bauer, Ryan J Gosselin, Barrett T Kitch, Jason E Cohen, Scott H Beegle, Renaud M Gueret, Aiman Tulaimat, Shazia Choudry, William Stigler, Hitesh Batra, Nidhi G Huff, Keith D Lamb, Trevor W Oetting, Nicholas M Mohr, Claine Judy, Shigeki Saito, Fayez M Kheir, Fayez Kheir, Adam B Schlichting, Angela Delsing, Daniel R Crouch, Mary Elmasri, Dina Ismail, Kyle R Dreyer, Thomas C Blakeman, Rebecca M Baron, Carolina Quintana Grijalba, Peter C Hou, Raghu Seethala, Imo Aisiku, Galen Henderson, Gyorgy Frendl, Sen-Kuang Hou, Robert L Owens, Ashley Schomer, Vesna Bumbasirevic, Bojan Jovanovic, Maja Surbatovic, Milic Veljovic
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ARDS ,medicine.medical_treatment ,030204 cardiovascular system & hematology ,Critical Care and Intensive Care Medicine ,Hyperoxemia ,Hypoxemia ,law.invention ,0302 clinical medicine ,law ,Fraction of inspired oxygen ,Oxygen therapy ,Prevalence ,Medicine ,Hypoxia ,Acute respiratory distress syndrome ,Hyperoxia ,Invasive mechanical ventilation ,Mortality ,Respiratory Distress Syndrome ,Hyperbaric Oxygenation ,Respiration ,lcsh:Medical emergencies. Critical care. Intensive care. First aid ,Intensive care unit ,Intensive Care Units ,Anesthesia ,Artificial ,medicine.symptom ,Human ,Artificial ventilation ,Intensive Care Unit ,NO ,03 medical and health sciences ,Intensive care ,Settore MED/41 - ANESTESIOLOGIA ,Humans ,business.industry ,Research ,Respiratory Distress Syndrome, Adult ,lcsh:RC86-88.9 ,medicine.disease ,Respiration, Artificial ,respiratory tract diseases ,Oxygen ,lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4] ,030228 respiratory system ,business - Abstract
Background Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55–100 mmHg) patients (P = 0.47). Conclusions Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073
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- 2020
5. Update in Interstitial Lung Disease 2020
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Shigeki Saito, Christopher J. Ryerson, Alyson W. Wong, Anna J. Podolanczuk, Joseph A. Lasky, and Oliver Eickelberg
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Pulmonary and Respiratory Medicine ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,MEDLINE ,Interstitial lung disease ,Critical Care and Intensive Care Medicine ,medicine.disease ,Virology ,Pulmonary, Sleep, and Critical Care Update ,Medicine ,Humans ,business ,Lung Diseases, Interstitial - Published
- 2021
6. Aspiration Risk Factors, Microbiology, and Empiric Antibiotics for Patients Hospitalized With Community-Acquired Pneumonia
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Judith Marin-Corral, Sergi Pascual-Guardia, Francesco Amati, Stefano Aliberti, Joan R Masclans, Nilam Soni, Alejandro Rodriguez, Oriol Sibila, Francisco Sanz, Giovanni Sotgiu, Antonio Anzueto, Katerina Dimakou, Roberta Petrino, Ewoudt van de Garde, Marcos I Restrepo, GLIMP investigators, Patricia Karina Aruj, Silvia Attorri, Enrique Barimboim, Juan Pablo Caeiro, María I Garzón, Victor Hugo Cambursano, V H Dr Cazaux A Adrian Ceccato, Julio Chertcoff, Florencia Lascar, Fernando Di Tulio, Ariel Cordon Díaz, Lautaro de Vedia, Maria Cristina Ganaha, Sandra Lambert, Gustavo Lopardo, Carlos M Luna, Alessio Gerardo Malberti, Nora Morcillo, Silvina Tartara, Claudia Pensotti, Betiana Pereyra, Pablo Gustavo Scapellato, Juan Pablo Stagnaro, Sonali Shah, Felix Lötsch, Florian Thalhammer, Kurt Anseeuw, Camille A Francois, Eva Van Braeckel, Jean Louis Vincent, Marcel Zannou Djimon, Jules Bashi, Roger Dodo, Simone Aranha Nouér, Peter Chipev, Milena Encheva, Darina Miteva, Diana Petkova, Adamou Dodo Balkissou, Eric Walter Pefura Yone, Bertrand Hugo Mbatchou Ngahane, Ning Shen, Jin-Fu Xu, Carlos Andres Bustamante Rico, Ricardo Buitrago, Fernando Jose Pereira Paternina, Jean-Marie Kayembe Ntumba, Vesna Vladic Carevic, Marko Jakopovic, Mateja Jankovic, Zinka Matkovic, Ivan Mitrecic, Marie-Laure Bouchy Jacobsson, Anette Bro Christensen, Uffe Christian Heitmann Bødtger, Christian Niels Meyer, Andreas Vestergaard Jensen, Gertrud Baunbæk-Knudsen, Pelle Trier Petersen, Stine Andersen, Ibrahim El-Said Abd El-Wahhab, Nesreen Elsayed Morsy, Hanaa Shafiek, Eman Sobh, Kedir Abdella Abdulsemed, Fabrice Bertrand, Christian Brun-Buisson, Etienne de Montmollin, Muriel Fartoukh, Jonathan Messika, Pierre Tattevin, Abdo Khoury, Bernard Ebruke, Michael Dreher, Martin Kolditz, Matthias Meisinger, Mathias W Pletz, Stefan Hagel, Jan Rupp, Tom Schaberg, Marc Spielmanns, Petra Creutz, Norton Suttorp, Beatrice Siaw-Lartey, Dimosthenis Papapetrou, Evdoxia Tsigou, Dimitrios Ampazis, Evangelos Kaimakamis, Mohit Bhatia, Raja Dhar, George D'Souza, Rajiv Garg, Parvaiz A Koul, P A Mahesh, B S Jayaraj, Kiran Vishnu Narayan, Hirennappa B Udnur, Shashi Bhaskara Krishnamurthy, Surya Kant, Rajesh Swarnakar, Sneha Limaye, Sundeep Salvi, Keihan Golshani, Vera M Keatings, Ignacio Martin-Loeches, Yasmin Maor, Jacob Strahilevitz, Paola Faverio, Salvatore Battaglia, Maria Carrabba, Piero Ceriana, Marco Confalonieri, Antonella d'Arminio Monforte, Bruno Del Prato, Marino De Rosa, Riccardo Fantini, Giuseppe Fiorentino, Maria Antonia Gammino, Francesco Menzella, Giuseppe Milani, Stefano Nava, Gerardo Palmiero, Barbra Gabrielli, Paolo Rossi, Claudio Sorino, Gundi Steinhilber, Alessandro Zanforlin, Ospedale San Luca, Fabio Franzetti, Manuela Carugati, Manuela Morosi, Elisa Monge, Mauro Carone, Vincenzo Patella, Simone Scarlata, Andrea Comel, Kiyoyasu Kurahashi, Zeina Aoun Bacha, Daniel Barajas Ugalde, Omar Ceballos Zuñiga, José F Villegas, Milic Medenica, Deebya Raj Mihsra, Poojan Shrestha, Elliott Ridgeon, Babatunde Ishola Awokola, Ogonna N O Adefuye Bolanle Olufunlola, Segaolu Olumide, Kingsley N Ukwaja, Muhammad Irfan, Lukasz Minarowski, Skoczyński Szymon, Felipe Froes, Pedro Leuschner, Mariana Meireles, Cláudia Ferrão, João Neves, Abel Salazar, Sofia B Ravara, Victoria Brocovschii, Doina Rusu, Cristina Toma, Daniela Chirita, Carmen Mihaela Dorobat, Alexei Birkun, Anna Kaluzhenina, Abdullah Almotairi, Zakeya Abdulbaqi Ali Bukhary, Jameela Edathodu, Amal Fathy, Abdullah Mushira Abdulaziz Enani, Nazik Eltayeb Mohamed, Jawed Ulhadi Memon, Abdelhaleem Bella, Serbia Nada Bogdanović, Branislava Milenkovic, Dragica Pesut, Luis Borderìas, Noel Manuel Bordon Garcia, Hugo Cabello Alarcón, Catia Cilloniz, Antoni Torres, Vicens Diaz-Brito, Xavier Casas, Alicia Encabo González, Maria Luisa Fernández-Almira, Medicina Interna, Miguel Gallego, Inmaculada Gaspar-GarcÍa, Juan González Del Castillo, Patricia Javaloyes Victoria, Elena Laserna Martínez, Rosa Malo de Molina, Pedro J Marcos, Rosario Menéndez, Ana Pando-Sandoval, Cristina Prat Aymerich, Alicia Lacoma de la Torre, Ignasi García-Olivé, Jordi Rello, Silvia Moyano, Ana Rodrigo-Troyano, Jordi Solé-Violán, Ane Uranga, Job Fm van Boven, Ester Vendrell Torra, Jordi Almirall Pujol, Charles Feldman, Ho Kee Yum, Inje Univ Arnauld Attannon Fiogbe, Ferdaous Yangui, Semra Bilaceroglu, Izmir Dr Levent Dalar, Ufuk Yilmaz, Artemii Bogomolov, Naheed Elahi, Devesh J Dhasmana, Andrew Feneley, Adam T Hill, Banu Rudran, Silvia Ruiz-Buitrago, Marion Campbell, Paul Whitaker, Alexander Youzguin, Anika Singanayagam, C Hancock, David Villafuerte, Karen S Allen, Veronica Brito, Jessica Dietz, Claire E Dysart, Susan M Kellie, Clement J Ricardo A Franco-Sadud, Garnet Meier, Mina Gaga, Thomas L Holland, Stephen P Bergin, Fayez Kheir, Mark Landmeier, Manuel Lois, Girish B Nair, Hemali Patel, Katherine Reyes, William Rodriguez-Cintron, Shigeki Saito, Julio Noda, Cecilia I Hinojosa, Stephanie M Levine, Luis F Reyes, Luis F Angel, K Scott Whitlow, John Hipskind, Kunal Sukhija, Vicken Totten, Richard G Wunderink, Ray D Shah, Kondwelani John Mateyo, Lorena Noriega, Ezequiel Alvarado, Mohamed Aman, Lucía Labra, Marin-Corral J., Pascual-Guardia S., Amati F., Aliberti S., Masclans J.R., Soni N., Rodriguez A., Sibila O., Sanz F., Sotgiu G., Anzueto A., Dimakou K., Petrino R., van de Garde E., Restrepo M.I., Aruj P.K., Attorri S., Barimboim E., Caeiro J.P., Garzon M.I., Cambursano V.H., Adrian Ceccato V.H.D.C.A., Chertcoff J., Lascar F., Di Tulio F., Diaz A.C., de Vedia L., Ganaha M.C., Lambert S., Lopardo G., Luna C.M., Malberti A.G., Morcillo N., Tartara S., Pensotti C., Pereyra B., Scapellato P.G., Stagnaro J.P., Shah S., Lotsch F., Thalhammer F., Anseeuw K., Francois C.A., Van Braeckel E., Vincent J.L., Djimon M.Z., Bashi J., Dodo R., Nouer S.A., Chipev P., Encheva M., Miteva D., Petkova D., Balkissou A.D., Pefura Yone E.W., Mbatchou Ngahane B.H., Shen N., Xu J.-F., Bustamante Rico C.A., Buitrago R., Pereira Paternina F.J., Kayembe Ntumba J.-M., Carevic V.V., Jakopovic M., Jankovic M., Matkovic Z., Mitrecic I., Bouchy Jacobsson M.-L., Christensen A.B., Heitmann Bodtger U.C., Meyer C.N., Jensen A.V., Baunbaek-knudsen G., Petersen P.T., Andersen S., El-Said Abd El-Wahhab I., Morsy N.E., Shafiek H., Sobh E., Abdulsemed K.A., Bertrand F., Brun-Buisson C., de Montmollin E., Fartoukh M., Messika J., Tattevin P., Khoury A., Ebruke B., Dreher M., Kolditz M., Meisinger M., Pletz M.W., Hagel S., Rupp J., Schaberg T., Spielmanns M., Creutz P., Suttorp N., Siaw-Lartey B., Papapetrou D., Tsigou E., Ampazis D., Kaimakamis E., Bhatia M., Dhar R., D'Souza G., Garg R., Koul P.A., Mahesh P.A., Jayaraj B.S., Narayan K.V., Udnur H.B., Krishnamurthy S.B., Kant S., Swarnakar R., Limaye S., Salvi S., Golshani K., Keatings V.M., Martin-Loeches I., Maor Y., Strahilevitz J., Faverio P., Battaglia S., Carrabba M., Ceriana P., Confalonieri M., Monforte A.D., Del Prato B., De Rosa M., Fantini R., Fiorentino G., Gammino M.A., Menzella F., Milani G., Nava S., Palmiero G., Gabrielli B., Rossi P., Sorino C., Steinhilber G., Zanforlin A., San Luca O., Franzetti F., Carugati M., Morosi M., Monge E., Carone M., Patella V., Scarlata S., Comel A., Kurahashi K., Bacha Z.A., Ugalde D.B., Zuniga O.C., Villegas J.F., Medenica M., Mihsra D.R., Shrestha P., Ridgeon E., Awokola B.I., Adefuye Bolanle Olufunlola O.N.O., Olumide S., Ukwaja K.N., Irfan M., Minarowski L., Szymon S., Froes F., Leuschner P., Meireles M., Ferrao C., Neves J., Abel Salazar, Ravara S.B., Brocovschii V., Rusu D., Toma C., Chirita D., Dorobat C.M., Birkun A., Kaluzhenina A., Almotairi A., Ali Bukhary Z.A., Edathodu J., Fathy A., Abdulaziz Enani A.M., Mohamed N.E., Memon J.U., Bella A., Bogdanovic S.N., Milenkovic B., Pesut D., Borderias L., Bordon Garcia N.M., Alarcon H.C., Cilloniz C., Torres A., Diaz-Brito V., Casas X., Gonzalez A.E., Fernandez-Almira M.L., Interna M., Gallego M., Gaspar-GarcIa I., Gonzalez del Castillo J., Victoria P.J., Martinez E.L., Malo de Molina R., Marcos P.J., Menendez R., Pando-Sandoval A., Aymerich C.P., Lacoma de la Torre A., Garcia-Olive I., Rello J., Moyano S., Rodrigo-Troyano A., Sole-Violan J., Uranga A., van Boven J.F., Torra E.V., Pujol J.A., Feldman C., Yum H.K., Arnauld Attannon Fiogbe I.U., Yangui F., Bilaceroglu S., Levent Dalar I.D., Yilmaz U., Bogomolov A., Elahi N., Dhasmana D.J., Feneley A., Hill A.T., Rudran B., Ruiz-Buitrago S., Campbell M., Whitaker P., Youzguin A., Singanayagam A., Hancock C., Villafuerte D., Allen K.S., Brito V., Dietz J., Dysart C.E., Kellie S.M., Ricardo A. Franco-Sadud C.J., Meier G., Gaga M., Holland T.L., Bergin S.P., Kheir F., Landmeier M., Lois M., Nair G.B., Patel H., Reyes K., Rodriguez-Cintron W., Saito S., Noda J., Hinojosa C.I., Levine S.M., Reyes L.F., Angel L.F., Whitlow K.S., Hipskind J., Sukhija K., Totten V., Wunderink R.G., Shah R.D., Mateyo K.J., Noriega L., Alvarado E., Aman M., Labra L., Marin-Corral, Judith, Pascual-Guardia, Sergi, Amati, Francesco, Aliberti, Stefano, R Masclans, Joan, Soni, Nilam, Rodriguez, Alejandro, Sibila, Oriol, Sanz, Francisco, Sotgiu, Giovanni, Anzueto, Antonio, Dimakou, Katerina, Petrino, Roberta, van de Garde, Ewoudt, I Restrepo, Marco, Investigators, Glimp, Karina Aruj, Patricia, Attorri, Silvia, Barimboim, Enrique, Pablo Caeiro, Juan, I Garzón, María, Hugo Cambursano, Victor, A Adrian Ceccato, V H Dr Cazaux, Chertcoff, Julio, Lascar, Florencia, Di Tulio, Fernando, Cordon Díaz, Ariel, de Vedia, Lautaro, Cristina Ganaha, Maria, Lambert, Sandra, Lopardo, Gustavo, M Luna, Carlo, Gerardo Malberti, Alessio, Morcillo, Nora, Tartara, Silvina, Pensotti, Claudia, Pereyra, Betiana, Gustavo Scapellato, Pablo, Pablo Stagnaro, Juan, Shah, Sonali, Lötsch, Felix, Thalhammer, Florian, Anseeuw, Kurt, A Francois, Camille, Van Braeckel, Eva, Louis Vincent, Jean, Zannou Djimon, Marcel, Bashi, Jule, Dodo, Roger, Aranha Nouér, Simone, Chipev, Peter, Encheva, Milena, Miteva, Darina, Petkova, Diana, Dodo Balkissou, Adamou, Walter Pefura Yone, Eric, Hugo Mbatchou Ngahane, Bertrand, Shen, Ning, Xu, Jin-Fu, Andres Bustamante Rico, Carlo, Buitrago, Ricardo, Jose Pereira Paternina, Fernando, Kayembe Ntumba, Jean-Marie, Vladic Carevic, Vesna, Jakopovic, Marko, Jankovic, Mateja, Matkovic, Zinka, Mitrecic, Ivan, Bouchy Jacobsson, Marie-Laure, Bro Christensen, Anette, Christian Heitmann Bødtger, Uffe, Niels Meyer, Christian, Vestergaard Jensen, Andrea, Baunbæk-Knudsen, Gertrud, Trier Petersen, Pelle, Andersen, Stine, El-Said Abd El-Wahhab, Ibrahim, Elsayed Morsy, Nesreen, Shafiek, Hanaa, Sobh, Eman, Abdella Abdulsemed, Kedir, Bertrand, Fabrice, Brun-Buisson, Christian, de Montmollin, Etienne, Fartoukh, Muriel, Messika, Jonathan, Tattevin, Pierre, Khoury, Abdo, Ebruke, Bernard, Dreher, Michael, Kolditz, Martin, Meisinger, Matthia, W Pletz, Mathia, Hagel, Stefan, Rupp, Jan, Schaberg, Tom, Spielmanns, Marc, Creutz, Petra, Suttorp, Norton, Siaw-Lartey, Beatrice, Papapetrou, Dimostheni, Tsigou, Evdoxia, Ampazis, Dimitrio, Kaimakamis, Evangelo, Bhatia, Mohit, Dhar, Raja, D'Souza, George, Garg, Rajiv, A Koul, Parvaiz, A Mahesh, P, S Jayaraj, B, Vishnu Narayan, Kiran, B Udnur, Hirennappa, Bhaskara Krishnamurthy, Shashi, Kant, Surya, Swarnakar, Rajesh, Limaye, Sneha, Salvi, Sundeep, Golshani, Keihan, M Keatings, Vera, Martin-Loeches, Ignacio, Maor, Yasmin, Strahilevitz, Jacob, Faverio, Paola, Battaglia, Salvatore, Carrabba, Maria, Ceriana, Piero, Confalonieri, Marco, d'Arminio Monforte, Antonella, Del Prato, Bruno, De Rosa, Marino, Fantini, Riccardo, Fiorentino, Giuseppe, Antonia Gammino, Maria, Menzella, Francesco, Milani, Giuseppe, Nava, Stefano, Palmiero, Gerardo, Gabrielli, Barbra, Rossi, Paolo, Sorino, Claudio, Steinhilber, Gundi, Zanforlin, Alessandro, San Luca, Ospedale, Franzetti, Fabio, Carugati, Manuela, Morosi, Manuela, Monge, Elisa, Carone, Mauro, Patella, Vincenzo, Scarlata, Simone, Comel, Andrea, Kurahashi, Kiyoyasu, Aoun Bacha, Zeina, Barajas Ugalde, Daniel, Ceballos Zuñiga, Omar, F Villegas, José, Medenica, Milic, Raj Mihsra, Deebya, Shrestha, Poojan, Ridgeon, Elliott, Ishola Awokola, Babatunde, O Adefuye Bolanle Olufunlola, Ogonna N, Olumide, Segaolu, N Ukwaja, Kingsley, Irfan, Muhammad, Minarowski, Lukasz, Szymon, Skoczyński, Froes, Felipe, Leuschner, Pedro, Meireles, Mariana, Ferrão, Cláudia, Neves, João, Salazar, Abel, B Ravara, Sofia, Brocovschii, Victoria, Rusu, Doina, Toma, Cristina, Chirita, Daniela, Mihaela Dorobat, Carmen, Birkun, Alexei, Kaluzhenina, Anna, Almotairi, Abdullah, Abdulbaqi Ali Bukhary, Zakeya, Edathodu, Jameela, Fathy, Amal, Mushira Abdulaziz Enani, Abdullah, Eltayeb Mohamed, Nazik, Ulhadi Memon, Jawed, Bella, Abdelhaleem, Nada Bogdanović, Serbia, Milenkovic, Branislava, Pesut, Dragica, Borderìas, Lui, Manuel Bordon Garcia, Noel, Cabello Alarcón, Hugo, Cilloniz, Catia, Torres, Antoni, Diaz-Brito, Vicen, Casas, Xavier, Encabo González, Alicia, Luisa Fernández-Almira, Maria, Interna, Medicina, Gallego, Miguel, Gaspar-GarcÍa, Inmaculada, González Del Castillo, Juan, Javaloyes Victoria, Patricia, Laserna Martínez, Elena, Malo de Molina, Rosa, J Marcos, Pedro, Menéndez, Rosario, Pando-Sandoval, Ana, Prat Aymerich, Cristina, Lacoma de la Torre, Alicia, García-Olivé, Ignasi, Rello, Jordi, Moyano, Silvia, Rodrigo-Troyano, Ana, Solé-Violán, Jordi, Uranga, Ane, Fm van Boven, Job, Vendrell Torra, Ester, Almirall Pujol, Jordi, Feldman, Charle, Kee Yum, Ho, Univ Arnauld Attannon Fiogbe, Inje, Yangui, Ferdaou, Bilaceroglu, Semra, Dr Levent Dalar, Izmir, Yilmaz, Ufuk, Bogomolov, Artemii, Elahi, Naheed, J Dhasmana, Devesh, Feneley, Andrew, T Hill, Adam, Rudran, Banu, Ruiz-Buitrago, Silvia, Campbell, Marion, Whitaker, Paul, Youzguin, Alexander, Singanayagam, Anika, Hancock, C, Villafuerte, David, S Allen, Karen, Brito, Veronica, Dietz, Jessica, E Dysart, Claire, M Kellie, Susan, A Franco-Sadud, Clement J Ricardo, Meier, Garnet, Gaga, Mina, L Holland, Thoma, P Bergin, Stephen, Kheir, Fayez, Landmeier, Mark, Lois, Manuel, B Nair, Girish, Patel, Hemali, Reyes, Katherine, Rodriguez-Cintron, William, Saito, Shigeki, Noda, Julio, I Hinojosa, Cecilia, M Levine, Stephanie, F Reyes, Lui, F Angel, Lui, Scott Whitlow, K, Hipskind, John, Sukhija, Kunal, Totten, Vicken, G Wunderink, Richard, D Shah, Ray, John Mateyo, Kondwelani, Noriega, Lorena, Alvarado, Ezequiel, Aman, Mohamed, Labra, Lucía, Marin-Corral, J, Pascual-Guardia, S, Amati, F, Aliberti, S, Masclans, J, Soni, N, Rodriguez, A, Sibila, O, Sanz, F, Sotgiu, G, Anzueto, A, Dimakou, K, Petrino, R, van de Garde, E, Restrepo, M, Aruj, P, Attorri, S, Barimboim, E, Caeiro, J, Garzon, M, Cambursano, V, Adrian Ceccato, V, Chertcoff, J, Lascar, F, Di Tulio, F, Diaz, A, de Vedia, L, Ganaha, M, Lambert, S, Lopardo, G, Luna, C, Malberti, A, Morcillo, N, Tartara, S, Pensotti, C, Pereyra, B, Scapellato, P, Stagnaro, J, Shah, S, Lotsch, F, Thalhammer, F, Anseeuw, K, Francois, C, Van Braeckel, E, Vincent, J, Djimon, M, Bashi, J, Dodo, R, Nouer, S, Chipev, P, Encheva, M, Miteva, D, Petkova, D, Balkissou, A, Pefura Yone, E, Mbatchou Ngahane, B, Shen, N, Xu, J, Bustamante Rico, C, Buitrago, R, Pereira Paternina, F, Kayembe Ntumba, J, Carevic, V, Jakopovic, M, Jankovic, M, Matkovic, Z, Mitrecic, I, Bouchy Jacobsson, M, Christensen, A, Heitmann Bodtger, U, Meyer, C, Jensen, A, Baunbaek-knudsen, G, Petersen, P, Andersen, S, El-Said Abd El-Wahhab, I, Morsy, N, Shafiek, H, Sobh, E, Abdulsemed, K, Bertrand, F, Brun-Buisson, C, de Montmollin, E, Fartoukh, M, Messika, J, Tattevin, P, Khoury, A, Ebruke, B, Dreher, M, Kolditz, M, Meisinger, M, Pletz, M, Hagel, S, Rupp, J, Schaberg, T, Spielmanns, M, Creutz, P, Suttorp, N, Siaw-Lartey, B, Papapetrou, D, Tsigou, E, Ampazis, D, Kaimakamis, E, Bhatia, M, Dhar, R, D'Souza, G, Garg, R, Koul, P, Mahesh, P, Jayaraj, B, Narayan, K, Udnur, H, Krishnamurthy, S, Kant, S, Swarnakar, R, Limaye, S, Salvi, S, Golshani, K, Keatings, V, Martin-Loeches, I, Maor, Y, Strahilevitz, J, Faverio, P, Battaglia, S, Carrabba, M, Ceriana, P, Confalonieri, M, Monforte, A, Del Prato, B, De Rosa, M, Fantini, R, Fiorentino, G, Gammino, M, Menzella, F, Milani, G, Nava, S, Palmiero, G, Gabrielli, B, Rossi, P, Sorino, C, Steinhilber, G, Zanforlin, A, San Luca, O, Franzetti, F, Carugati, M, Morosi, M, Monge, E, Carone, M, Patella, V, Scarlata, S, Comel, A, Kurahashi, K, Bacha, Z, Ugalde, D, Zuniga, O, Villegas, J, Medenica, M, Mihsra, D, Shrestha, P, Ridgeon, E, Awokola, B, Adefuye Bolanle Olufunlola, O, Olumide, S, Ukwaja, K, Irfan, M, Minarowski, L, Szymon, S, Froes, F, Leuschner, P, Meireles, M, Ferrao, C, Neves, J, Abel, S, Ravara, S, Brocovschii, V, Rusu, D, Toma, C, Chirita, D, Dorobat, C, Birkun, A, Kaluzhenina, A, Almotairi, A, Ali Bukhary, Z, Edathodu, J, Fathy, A, Abdulaziz Enani, A, Mohamed, N, Memon, J, Bella, A, Bogdanovic, S, Milenkovic, B, Pesut, D, Borderias, L, Bordon Garcia, N, Alarcon, H, Cilloniz, C, Torres, A, Diaz-Brito, V, Casas, X, Gonzalez, A, Fernandez-Almira, M, Interna, M, Gallego, M, Gaspar-GarcIa, I, Gonzalez del Castillo, J, Victoria, P, Martinez, E, Malo de Molina, R, Marcos, P, Menendez, R, Pando-Sandoval, A, Aymerich, C, Lacoma de la Torre, A, Garcia-Olive, I, Rello, J, Moyano, S, Rodrigo-Troyano, A, Sole-Violan, J, Uranga, A, van Boven, J, Torra, E, Pujol, J, Feldman, C, Yum, H, Arnauld Attannon Fiogbe, I, Yangui, F, Bilaceroglu, S, Levent Dalar, I, Yilmaz, U, Bogomolov, A, Elahi, N, Dhasmana, D, Feneley, A, Hill, A, Rudran, B, Ruiz-Buitrago, S, Campbell, M, Whitaker, P, Youzguin, A, Singanayagam, A, Villafuerte, D, Allen, K, Brito, V, Dietz, J, Dysart, C, Kellie, S, Ricardo, A, Meier, G, Gaga, M, Holland, T, Bergin, S, Kheir, F, Landmeier, M, Lois, M, Nair, G, Patel, H, Reyes, K, Rodriguez-Cintron, W, Saito, S, Noda, J, Hinojosa, C, Levine, S, Reyes, L, Angel, L, Whitlow, K, Hipskind, J, Sukhija, K, Totten, V, Wunderink, R, Shah, R, Mateyo, K, Noriega, L, Alvarado, E, Aman, M, and Labra, L
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Male ,Pulmonary and Respiratory Medicine ,medicine.drug_class ,Aspiration risk ,Antibiotics ,Nursing home resident ,Settore MED/10 - Malattie Dell'Apparato Respiratorio ,Critical Care and Intensive Care Medicine ,Microbiology ,anaerobic ,aspiration ,bacteria ,pneumonia ,risk factors ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Community-acquired pneumonia ,Taverne ,Anti-Bacterial Agent ,medicine ,Humans ,Community-Acquired Infection ,030212 general & internal medicine ,Stroke ,Aged ,Aged, 80 and over ,business.industry ,Respiratory Aspiration ,Middle Aged ,medicine.disease ,Antibiotic coverage ,Anti-Bacterial Agents ,Community-Acquired Infections ,Hospitalization ,Pneumonia ,030228 respiratory system ,Risk factors ,risk factor ,Female ,Underweight ,medicine.symptom ,business ,Cardiology and Cardiovascular Medicine - Abstract
Background: Aspiration community-acquired pneumonia (ACAP) and community-acquired pneumonia (CAP) in patients with aspiration risk factors (AspRFs) are infections associated with anaerobes, but limited evidence suggests their pathogenic role. Research Question: What are the aspiration risk factors, microbiology patterns, and empiric anti-anaerobic use in patients hospitalized with CAP? Study Design and Methods: This is a secondary analysis of GLIMP, an international, multicenter, point-prevalence study of adults hospitalized with CAP. Patients were stratified into three groups: (1) ACAP, (2) CAP/AspRF+ (CAP with AspRF), and (3) CAP/AspRF- (CAP without AspRF). Data on demographics, comorbidities, microbiological results, and anti-anaerobic antibiotics were analyzed in all groups. Patients were further stratified in severe and nonsevere CAP groups. Results: We enrolled 2,606 patients with CAP, of which 193 (7.4%) had ACAP. Risk factors independently associated with ACAP were male, bedridden, underweight, a nursing home resident, and having a history of stroke, dementia, mental illness, and enteral tube feeding. Among non-ACAP patients, 1,709 (70.8%) had CAP/AspRF+ and 704 (29.2%) had CAP/AspRF-. Microbiology patterns including anaerobes were similar between CAP/AspRF-, CAP/AspRF+ and ACAP (0.0% vs 1.03% vs 1.64%). Patients with severe ACAP had higher rates of total gram-negative bacteria (64.3% vs 44.3% vs 33.3%, P =.021) and lower rates of total gram-positive bacteria (7.1% vs 38.1% vs 50.0%, P 50% in all groups) independent of AspRFs or ACAP received specific or broad-spectrum anti-anaerobic coverage antibiotics. Interpretation: Hospitalized patients with ACAP or CAP/AspRF+ had similar anaerobic flora compared with patients without aspiration risk factors. Gram-negative bacteria were more prevalent in patients with severe ACAP. Despite having similar microbiological flora between groups, a large proportion of CAP patients received anti-anaerobic antibiotic coverage.
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- 2021
7. Histone Deacetylase 8 (HDAC8) Inhibition Ameliorates Pulmonary Fibrosis, Likely by Activating Anti-Fibrotic SREBP1c-COX-PGE2 Signaling and Inhibiting Pro-Fibrotic PDGF-FOXM1 Signaling
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Yao-Zhong Liu, J.A. Lasky, J.K. Kolls, Shigeki Saito, and Yan Zhuang
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Anti fibrotic ,biology ,business.industry ,Pulmonary fibrosis ,FOXM1 ,medicine ,biology.protein ,Cancer research ,HDAC8 ,medicine.disease ,business ,Platelet-derived growth factor receptor - Published
- 2020
8. Microbiological testing of adults hospitalised with community-acquired pneumonia: an international study
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Manuela Carugati, Stefano Aliberti, Luis Felipe Reyes, Ricardo Franco Sadud, Muhammad Irfan, Cristina Prat, Nilam J. Soni, Paola Faverio, Andrea Gori, Francesco Blasi, Marcos I. Restrepo, Patricia Karina Aruj, Silvia Attorri, Enrique Barimboim, Juan Pablo Caeiro, María I. Garzón, Victor Hugo Cambursano, Adrian Ceccato, Julio Chertcoff, Florencia Lascar, Fernando Di Tulio, Ariel Cordon Díaz, Lautaro de Vedia, Maria Cristina Ganaha, Sandra Lambert, Gustavo Lopardo, Carlos M. Luna, Alessio Gerardo Malberti, Nora Morcillo, Silvina Tartara, Claudia Pensotti, Betiana Pereyra, Pablo Gustavo Scapellato, Juan Pablo Stagnaro, Florencio Varela, Sonali Shah, Felix Lötsch, Florian Thalhammer, Kurt Anseeuw, Camille A. Francois, Eva Van Braeckel, Jean Louis Vincent, Marcel Zannou Djimon, Jules Bashi, Roger Dodo, Simone Aranha Nouér, Peter Chipev, Milena Encheva, Darina Miteva, Diana Petkova, Adamou Dodo Balkissou, Eric Walter Pefura Yone, Bertrand Hugo Mbatchou Ngahane, Ning Shen, Jin-fu Xu, Carlos Andres Bustamante Rico, Ricardo Buitrago, Fernando Jose Pereira Paternina, Jean-Marie Kayembe Ntumba, Vesna Vladic Carevic, Marko Jakopovic, Mateja Jankovic, Zinka Matkovic, Ivan Mitrecic, Marie-Laure Bouchy Jacobsson, Anette Bro Christensen, Uffe Christian Heitmann Bødtger, Christian Niels Meyer, Andreas Vestergaard Jensen, Gertrud Baunbæk-Knudsen, Pelle Trier Petersen, Stine Andersen, Ibrahim El-Said Abd El-Wahhab, Nesreen Elsayed Morsy, Hanaa Shafiek, Eman Sobh, Kedir Abdella Abdulsemed, Fabrice Bertrand, Christian Brun-Buisson, Etienne de Montmollin, Muriel Fartoukh, Jonathan Messika, Pierre Tattevin, Abdo Khoury, Bernard Ebruke, Michael Dreher, Martin Kolditz, Matthias Meisinger, Mathias W. Pletz, Stefan Hagel, Jan Rupp, Tom Schaberg, Marc Spielmanns, Petra Creutz, Norton Suttorp, Beatrice Siaw-Lartey, Katerina Dimakou, Dimosthenis Papapetrou, Evdoxia Tsigou, Dimitrios Ampazis, Evangelos Kaimakamis, Mina Gaga, Mohit Bhatia, Raja Dhar, George D'Souza, Rajiv Garg, Parvaiz A. Koul, P.A. Mahesh, B.S. Jayaraj, Kiran Vishnu Narayan, Hirennappa B. Udnur, Shashi Bhaskara Krishnamurthy, Surya Kant, Rajesh Swarnakar, Sneha Limaye, Sundeep Salvi, Keihan Golshani, Vera M. Keatings, Ignacio Martin-Loeches, Yasmin Maor, Jacob Strahilevitz, Salvatore Battaglia, Maria Carrabba, Piero Ceriana, Marco Confalonieri, Antonella d'Arminio Monforte, Bruno Del Prato, Marino De Rosa, Riccardo Fantini, Giuseppe Fiorentino, Maria Antonia Gammino, Francesco Menzella, Giuseppe Milani, Stefano Nava, Gerardo Palmiero, Roberta Petrino, Barbra Gabrielli, Paolo Rossi, Claudio Sorino, Gundi Steinhilber, Alessandro Zanforlin, Fabio Franzetti, Manuela Morosi, Elisa Monge, Mauro Carone, Vincenzo Patella, Simone Scarlata, Andrea Comel, Kiyoyasu Kurahashi, Zeina Aoun Bacha, Daniel Barajas Ugalde, Omar Ceballos Zuñiga, José F. Villegas, Milic Medenica, E.M.W. van de Garde, Deebya Raj Mihsra, Poojan Shrestha, Elliott Ridgeon, Babatunde Ishola Awokola, Ogonna N.O. Nwankwo, Adefuye Bolanle Olufunlola, Segaolu Olumide, Kingsley N. Ukwaja, Lukasz Minarowski, Skoczyński Szymon, Felipe Froes, Pedro Leuschner, Mariana Meireles, Sofia B Ravara, Victoria Brocovschii, Chesov Ion, Doina Rusu, Cristina Toma, Daniela Chirita, Carmen Mihaela Dorobat, Alexei Birkun, Anna Kaluzhenina, Abdullah Almotairi, Zakeya Abdulbaqi Ali Bukhary, Jameela Edathodu, Amal Fathy, Abdullah Mushira Abdulaziz Enani, Nazik Eltayeb Mohamed, Jawed Ulhadi Memon, Abdelhaleem Bella, Nada Bogdanović, Branislava Milenkovic, Dragica Pesut, Charles Feldman, Ho Kee Yum, Luis Borderìas, Noel Manuel Bordon Garcia, Hugo Cabello Alarcón, Catia Cilloniz, Antoni Torres, Vicens Diaz-Brito, Xavier Casas, Alicia Encabo González, Maria Luisa Fernández-Almira, Miguel Gallego, Inmaculada Gaspar-GarcÍa, Juan González del Castillo, Patricia Javaloyes Victoria, Elena Laserna Martínez, Rosa Malo de Molina, Pedro J. Marcos, Rosario Menéndez, Ana Pando-Sandoval, Cristina Prat Aymerich, Jordi Rello, Silvia Moyano, Francisco Sanz, Oriol Sibila, Ana Rodrigo-Troyano, Jordi Solé-Violán, Ane Uranga, Job F.M. van Boven, Ester Vendrell Torra, Jordi Almirall Pujol, Arnauld Attannon Fiogbe, Ferdaous Yangui, Semra Bilaceroglu, Levent Dalar, Ufuk Yilmaz, Artemii Bogomolov, Naheed Elahi, Devesh J. Dhasmana, Andrew Feneley, Rhiannon Ions, Julie Skeemer, Gerrit Woltmann, Carole Hancock, Adam T. Hill, Banu Rudran, Silvia Ruiz-Buitrago, Marion Campbell, Paul Whitaker, Alexander Youzguin, Anika Singanayagam, Karen S. Allen, Veronica Brito, Jessica Dietz, Claire E. Dysart, Susan M. Kellie, Ricardo A. Franco-Sadud, Garnet Meier, Thomas L. Holland, Stephen P. Bergin, Fayez Kheir, Mark Landmeier, Manuel Lois, Girish B. Nair, Hemali Patel, Katherine Reyes, William Rodriguez-Cintron, Shigeki Saito, Julio Noda, Cecilia I. Hinojosa, Stephanie M. Levine, Luis F. Angel, Antonio Anzueto, K. Scott Whitlow, John Hipskind, Kunal Sukhija, Vicken Totten, Richard G. Wunderink, Ray D. Shah, Kondwelani John Mateyo, Lorena Noriega, Ezequiel Alvarado, Mohamed Aman, Lucía Labra, Carugati M., Aliberti S., Reyes L.F., Sadud R.F., Irfan M., Prat C., Soni N.J., Faverio P., Gori A., Blasi F., Restrepo M.I., Aruj P.K., Attorri S., Barimboim E., Caeiro J.P., Garzon M.I., Cambursano V.H., Ceccato A., Chertcoff J., Diaz A.C., De Vedia L., Ganaha M.C., Lambert S., Lopardo G., Luna C.M., Malberti A.G., Morcillo N., Tartara S., Pensotti C., Pereyra B., Scapellato P.G., Stagnaro J.P., Shah S., Lotsch F., Thalhammer F., Anseeuw K., Francois C.A., Van Braeckel E., Vincent J.L., Djimon M.Z., Bashi J., Dodo R., Nouer S.A., Chipev P., Encheva M., Miteva D., Petkova D., Balkissou A.D., Yone E.W.P., Ngahane B.H.M., Shen N., Xu J.-F., Rico C.A.B., Buitrago R., Paternina F.J.P., Ntumba J.-M.K., Carevic V.V., Jakopovic M., Jankovic M., Matkovic Z., Mitrecic I., Jacobsson M.L.B., Christensen A.B., Bodtger U.C.H., Meyer C.N., Jensen A.V., Baunbaek-Knudsen G., Petersen P.T., Andersen S., Abd El-Wahhab I.E.-S., Morsy N.E., Shafiek H., Sobh E., Abdulsemed K.A., Bertrand F., Brun-Buisson C., De Montmollin E., Fartoukh M., Messika J., Tattevin P., Khoury A., Ebruke B., Dreher M., Kolditz M., Meisinger M., Pletz M.W., Hagel S., Rupp J., Schaberg T., Spielmanns M., Creutz P., Suttorp N., Siaw-Lartey B., Dimakou K., Papapetrou D., Tsigou E., Ampazis D., Kaimakamis E., Gaga M., Bhatia M., Dhar R., D'Souza G., Garg R., Koul P.A., Mahesh P.A., Jayaraj B.S., Narayan K.V., Udnur H.B., Krishnamurthy S.B., Kant S., Swarnakar R., Limaye S., Salvi S., Golshani K., Keatings V.M., Martin-Loeches I., Maor Y., Strahilevitz J., Battaglia S., Carrabba M., Ceriana P., Confalonieri M., Monforte A.D., Del Prato B., De Rosa M., Fantini R., Fiorentino G., Gammino M.A., Menzella F., Milani G., Nava S., Palmiero G., Petrino R., Gabrielli B., Rossi P., Sorino C., Steinhilber G., Zanforlin A., Franzetti F., Morosi M., Monge E., Carone M., Patella V., Scarlata S., Comel A., Kurahashi K., Bacha Z.A., Ugalde D.B., Zuniga O.C., Villegas J.F., Medenica M., Van De Garde E.M.W., Mihsra D.R., Medicine I., Shrestha P., Ridgeon E., Awokola B.I., Nwankwo O.N.O., Olufunlola A.B., Olumide S., Ukwaja K.N., Minarowski L., Szymon S., Froes F., Leuschner P., Meireles M., Ferrao C., Neves J., De Medicina S., Ravara S.B., Brocovschii V., Ion C., Rusu D., Tom C., Chirita D., Dorobat C.M., Birkun A., Kaluzhenina A., Almotairi A., Bukhary Z.A.A., Edathodu J., Fathy A., Enani A.M.A., Mohamed N.E., Memon J.U., Bella A., Bogdanovic N., Milenkovic B., Pesut D., Feldman C., Yum H.K., Borderias L., Garcia N.M.B., Alarcon H.C., Cilloniz C., Torres A., Diaz-Brito V., Casas X., Gonzalez A.E., Fernandez-Almira M.L., Gallego M., Gaspar-Garcia I., Del Castillo J.G., Victoria P.J., Martinez E.L., De Molina R.M., Marcos P.J., Menendez R., Pando-Sandoval A., Aymerich C.P., Rello J., Moyano S., Sanz F., Sibila O., Rodrigo-Troyano A., Sole-Violan J., Uranga A., Van Boven J.F.M., Torra E.V., Pujol J.A., Fiogbe A.A., Yangui F., Bilaceroglu S., Dalar L., Yilmaz U., Bogomolov A., Elahi N., Feneley A., Ions R., Skeemer J., Woltmann G., Hancock C., Hill A.T., Rudran B., Ruiz-Buitrago S., Campbell M., Whitaker P., Youzguin A., Singanayagam A., Allen K.S., Brito V., Dietz J., Dysart C.E., Kellie S.M., Franco-Sadud R.A., Meier G., Holland T.L., Bergin S.P., Kheir F., Landmeier M., Lois M., Nair G.B., Patel H., Reyes K., Rodriguez-Cintron W., Saito S., Noda J., Hinojosa C.I., Levine S.M., Angel L.F., Anzueto A., Whitlow K.S., Hipskind J., Sukhija K., Totten V., Wunderink R.G., Shah R.D., Mateyo K.J., Dhasmana D.J., Noriega L., Alvarado E., Aman M., Labra L., Carugati, M, Aliberti, S, Reyes, L, Franco Sadud, R, Irfan, M, Prat, C, Soni, N, Faverio, P, Gori, A, Blasi, F, and Restrepo, M
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0301 basic medicine ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,community-acquired pneumonia ,Community-acquired pneumonia ,Patients ,Concordance ,030106 microbiology ,Respiratory System ,lcsh:Medicine ,Settore MED/10 - Malattie Dell'Apparato Respiratorio ,GUIDELINES ,Pneumònia adquirida a la comunitat ,Sputum culture ,Serology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,MANAGEMENT ,Blood culture ,030212 general & internal medicine ,POPULATION ,pneumonia, Methicillin-resistant Staphylococcus aureus Pneumonia ,Science & Technology ,medicine.diagnostic_test ,business.industry ,MORTALITY ,lcsh:R ,Microbiologia mèdica ,Original Articles ,Guideline ,Pneumonia ,Medical microbiology ,medicine.disease ,Microbiological ,ETIOLOGY ,Diagnostic testing ,REQUIRING HOSPITALIZATION ,business ,Life Sciences & Biomedicine ,Cohort study - Abstract
This study aimed to describe real-life microbiological testing of adults hospitalised with community-acquired pneumonia (CAP) and to assess concordance with the 2007 Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) and 2011 European Respiratory Society (ERS) CAP guidelines. This was a cohort study based on the Global Initiative for Methicillin-resistant Staphylococcus aureus Pneumonia (GLIMP) database, which contains point-prevalence data on adults hospitalised with CAP across 54 countries during 2015. In total, 3702 patients were included. Testing was performed in 3217 patients, and included blood culture (71.1%), sputum culture (61.8%), Legionella urinary antigen test (30.1%), pneumococcal urinary antigen test (30.0%), viral testing (14.9%), acute-phase serology (8.8%), bronchoalveolar lavage culture (8.4%) and pleural fluid culture (3.2%). A pathogen was detected in 1173 (36.5%) patients. Testing attitudes varied significantly according to geography and disease severity. Testing was concordant with IDSA/ATS and ERS guidelines in 16.7% and 23.9% of patients, respectively. IDSA/ATS concordance was higher in Europe than in North America (21.5% versus 9.8%; p, Testing practices vary based on geography and disease severity, and IDSA/ATS/ERS testing recommendations are rarely followed http://ow.ly/80Iy30lxo1c
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- 2018
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9. Using Bronchoscopic Lung Cryobiopsy and a Genomic Classifier in the Multidisciplinary Diagnosis of Diffuse Interstitial Lung Diseases
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Philip J. Daroca, Fayez Kheir, Gerald J. Berry, Marjorie E. Bateman, Reinaldo Rampolla, David L. Smith, David Weill, Ramsy Abdelghani, Lisa Diethelm, Ala Alkhatib, Shigeki Saito, and Joseph A. Lasky
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Pulmonary and Respiratory Medicine ,Male ,medicine.medical_specialty ,Concordance ,Biopsy ,Critical Care and Intensive Care Medicine ,03 medical and health sciences ,Idiopathic pulmonary fibrosis ,0302 clinical medicine ,Bronchoscopy ,DLCO ,Usual interstitial pneumonia ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,Medical diagnosis ,Lung ,Aged ,Retrospective Studies ,Cryopreservation ,medicine.diagnostic_test ,business.industry ,Interstitial lung disease ,Reproducibility of Results ,Genomics ,respiratory system ,medicine.disease ,Confidence interval ,030228 respiratory system ,Diffuse Lung Disease: Original Research ,Female ,Cardiology and Cardiovascular Medicine ,business ,Lung Diseases, Interstitial ,Tomography, X-Ray Computed - Abstract
Background Challenges remain for establishing a specific diagnosis in cases of interstitial lung disease (ILD). Bronchoscopic lung cryobiopsy (BLC) has impacted the diagnostic impression and confidence of multidisciplinary discussions (MDDs) in the evaluation of ILD. Reports indicate that a genomic classifier (GC) can distinguish usual interstitial pneumonia (UIP) from non-UIP. Research Question What is the impact of sequentially presented data from BLC and GC on the diagnostic confidence of MDDs in diagnosing ILD? Study Design and Methods Two MDD teams met to discuss 24 patients with ILD without a definitive UIP pattern. MDD1 sequentially reviewed clinical-radiologic findings, BLC, and GC. MDD2 sequentially reviewed GC before BLC. At each step in the process the MDD diagnosis and confidence level were recorded. Results MDD1 had a significant increase in diagnostic confidence, from 43% to 93% (P = .023), in patients with probable UIP after the addition of GC to BLC. MDD2 had an increase in diagnostic confidence, from 27% to 73% (P = .074), after the addition of BLC to GC. The concordance coefficients and percentage agreement of categorical idiopathic pulmonary fibrosis (IPF) and non-IPF diagnoses were as follows: GC vs MDD1: 0.92, 96%; GC vs MDD2: 0.83, 92%; BLC1 vs MDD1: 0.67, 83%; BLC2 vs MDD2: 0.66, 83%. Interpretation GC increased diagnostic confidence when added to BLC for patients with a probable UIP pattern, and in appropriate clinical settings can be used without BLC. In contrast, BLC had the greatest impact regarding a specific diagnosis when the likelihood of UIP was considered low following clinical-radiographic review.
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- 2019
10. Review: Pharmacotherapy for smoking cessation
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Shigeki Saito, Karin Halvorson, and Chok Limsuwat
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lcsh:RC705-779 ,Bupropion ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Nicotine patch ,lcsh:Diseases of the respiratory system ,Nicotine replacement therapy ,smoking cessation ,nicotine replacement therapy ,Nicotine ,varenicline ,bupropion: e-cigarettes ,chemistry.chemical_compound ,chemistry ,Nicotine gum ,Internal medicine ,mental disorders ,behavior and behavior mechanisms ,medicine ,Smoking cessation ,business ,Varenicline ,Nicotine replacement ,medicine.drug - Abstract
Smoking is associated with numerous cancers and atherosclerosis. Smoking cessationhas substantial potential in reducing morbidity and mortality worldwide. The initial steps “5 A’s”(Ask, Advise, Assess, Assist, Arrange) should be applied in all patients. Behavioral counselingand pharmacotherapy are both effective, but the combination of the two is more effective thaneither alone. The first-line pharmacotherapy includes nicotine replacement, bupropion, andvarenicline. Nicotine replacement therapy (NRT) consists of long-active formulations, such asin a patch, and short-acting formulations such as in gum, lozenge, inhaler, and nasal spray. Ascompared to placebo, NRT increases the chances of quitting smoking. Nicotine replacementtherapy does not increase cardiovascular risk and is safe in patients with cardiovasculardisease. Sustained-release bupropion is more effective than nicotine patches and can becombined with nicotine patches. Buprenorphine is generally well tolerated, except that it lowersseizure threshold and is contraindicated in patients with seizure disorders. Varenicline alsosignificantly improves the success rate of smoking cessation. The latest evidence suggeststhat varenicline is not associated with an increased risk of neuropsychiatric or cardiovascularevents. In conclusion, the use of NRT (nicotine patch + nicotine gum/lozenge/inhaler/spray),bupropion (with NRT), or varenicline is strongly recommended for smoking cessation, unlessthey are contraindicated.
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- 2018
11. Effect of ruxolitinib therapy on the quality-of-life of Japanese patients with myelofibrosis
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Taro Amagasaki, Katsuto Takenaka, Hikaru Okada, Hiroshi Handa, Keita Kirito, Shinichiro Okamoto, Kenji Oritani, Shiho Wakase, Norio Komatsu, Kazuya Shimoda, Koichi Akashi, Shigeki Saito, Tetsuzo Tauchi, Kohshi Ohishi, and Kojiro Shimozuma
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Adult ,Male ,Oncology ,Ruxolitinib ,medicine.medical_specialty ,03 medical and health sciences ,0302 clinical medicine ,Quality of life ,Internal medicine ,Nitriles ,medicine ,Humans ,Myelofibrosis ,Protein Kinase Inhibitors ,Aged ,Aged, 80 and over ,business.industry ,Symptom burden ,General Medicine ,Janus Kinase 2 ,Middle Aged ,medicine.disease ,Pyrimidines ,Treatment Outcome ,Primary Myelofibrosis ,030220 oncology & carcinogenesis ,Quality of Life ,Pyrazoles ,Female ,business ,030215 immunology ,medicine.drug - Abstract
Myelofibrosis (MF) is associated with a significant symptom burden that severely impacts patient quality-of-life (QoL). Ruxolitinib, a potent Janus kinase 1 (JAK1)/JAK2 inhibitor, led to substantial improvements in splenomegaly, MF-associated symptoms, and QoL in the phase 3 COMFORT studies, proving superior to placebo and best available therapy. This study evaluated the effect of ruxolitinib on symptoms and QoL in Japanese patients with MF.A pooled analysis of studies A2202 (NCT01392443) and AJP01 (NCT02087059) of ruxolitinib in Japanese patients with MF (n = 81) was conducted. Changes in total symptom score (TSS) and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 were summarized.Most patients received a starting dose of 15 or 20 mg twice daily (BID) and had a final titrated dose of ≥10 mg BID. Overall, 67.7% (44/65) achieved a ≥50% reduction from baseline in TSS at week 24. Reductions in TSS were seen in every dose group; the greatest reductions occurred in patients with a final titrated dose of 20 or 25 mg BID. Improvements in QoL were seen in patients who achieved a ≥50% reduction in TSS. Generally, improvements in TSS and individual symptoms correlated with reductions in spleen size, with those having a ≥35% reduction in spleen volume having the greatest improvements.Consistent with COMFORT-I, ruxolitinib provided substantial improvements in symptoms and QoL in Japanese patients with MF, with higher doses of ruxolitinib associated with better responses.
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- 2018
12. Switching to nilotinib in patients with chronic myeloid leukemia in chronic phase with molecular suboptimal response to frontline imatinib: SENSOR final results and BIM polymorphism substudy
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Shigeki Saito, Tatsuya Kawaguchi, Junichi Tsukada, Toshihiro Miyamoto, Hisashi Tsurumi, Masafumi Taniwaki, Kohmei Kubo, Hikaru Okada, Makoto Aoki, Kazuhito Yamamoto, Tomoko Hata, Shinya Kimura, Midori Kondo, Itaru Matsumura, Masamitsu Yanada, Koichi Miyamura, Kazuma Ohyashiki, Kuniaki Meguro, Hideo Hyodo, Masayuki Hino, Masahide Yamamoto, Mitsune Tanimoto, and Seiji Tadokoro
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Adult ,Male ,0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,medicine.drug_class ,Antineoplastic Agents ,Tyrosine-kinase inhibitor ,Young Adult ,03 medical and health sciences ,European LeukemiaNet ,0302 clinical medicine ,hemic and lymphatic diseases ,Internal medicine ,Clinical endpoint ,Humans ,Medicine ,Progression-free survival ,Adverse effect ,Protein Kinase Inhibitors ,Aged ,Aged, 80 and over ,Polymorphism, Genetic ,Drug Substitution ,business.industry ,Myeloid leukemia ,Imatinib ,Hematology ,Middle Aged ,Surgery ,Pyrimidines ,Treatment Outcome ,030104 developmental biology ,Nilotinib ,030220 oncology & carcinogenesis ,Leukemia, Myeloid, Chronic-Phase ,Imatinib Mesylate ,Female ,business ,medicine.drug - Abstract
Optimal management of patients with chronic myeloid leukemia in chronic phase with suboptimal molecular response (MR) to frontline imatinib is undefined. We report final results from SENSOR, which evaluated efficacy/safety of nilotinib in this setting. A substudy assessed whether BIM polymorphisms impacted response to nilotinib. In this single-arm, multicenter study, Japanese patients with suboptimal MR per European LeukemiaNet 2009 criteria (complete cytogenetic response, but not major MR [MMR]) after ≥18 months of frontline imatinib received nilotinib 400mg twice daily for 24 months. MR, BCR-ABL1 mutations/variants, and BIM polymorphisms were evaluated in a central laboratory. Primary endpoint was the MMR rate at 12 months (null hypothesis of 40%). Of 45 patients (median exposure, 22.08 months), 39 completed the study and six discontinued. At 12 and 24 months, 51.1% (95% CI, 35.8%-66.3%) and 66.7% (95% CI, 51.0%-80.0%) achieved MMR, respectively. Cumulative MMR incidence by 24 months was 75.6%. Of 40 patients analyzed, 10 of 12 (83.3%) with and 17 of 28 (60.7%) without BIM polymorphisms achieved MMR at 24 months. The safety profile was manageable with dose reductions and interruptions. Nilotinib provided clinical benefit for patients with suboptimal response to imatinib, and BIM polymorphisms did not influence MMR achievement. ClinicalTrials.gov: NCT01043874.
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- 2016
13. Pharmacotherapy and adjunctive treatment for idiopathic pulmonary fibrosis (IPF)
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Joseph A. Lasky, Yasuhiro Kondoh, Shigeki Saito, Jay K. Kolls, and Ala Alkhatib
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Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,business.industry ,Guideline ,Pirfenidone ,Review Article ,medicine.disease ,CTGF ,03 medical and health sciences ,chemistry.chemical_compound ,Idiopathic pulmonary fibrosis ,0302 clinical medicine ,Pharmacotherapy ,030228 respiratory system ,Tolerability ,chemistry ,Internal medicine ,Adjunctive treatment ,medicine ,Nintedanib ,030212 general & internal medicine ,business ,medicine.drug - Abstract
Idiopathic pulmonary fibrosis (IPF) is an advancing and fatal lung disease with increasing incidence and prevalence. Nintedanib and pirfenidone were approved by the FDA for the treatment of IPF in 2014 based on positive phase 3 trials, and both of these antifibrotic drugs are conditionally recommended in the 2015 ATS/ERS/JRS/ALAT Clinical Practice Guideline. Although an improvement over previously suggested therapies, their capacity to reduce, but not completely arrest or improve, lung function over time presents an opportunity for novel or add-on pharmacologic agents. The purpose of this review is to deliver a brief overview of the results of phase 3/4 IPF trials with pirfenidone and nintedanib, as well as highlight encouraging results of phase 1/2 trials with novel therapies. Long-term studies indicate that pirfenidone and nintedanib are effective IPF treatments, with acceptable safety and tolerability. The combination of pirfenidone and nintedanib appear safe. Promising results have recently been made public for several phase 2 trials with novel targets, including the autotaxin-lysophosphatidic acid (ATX/LPA) pathway, connective tissue growth factor (CTGF), pentraxin-2, G protein-coupled receptor agonists/antagonists, αvβ6 integrin, and galectin-3. Results of treatments directed at gastro-esophageal reflux in patients with IPF have also been published. Currently, monotherapy with pirfenidone or nintedanib is the mainstay of pharmacological treatment for IPF. Innovative therapies along with combinations of pharmacological agents hold great promise for the future.
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- 2019
14. Influence of Race on BNP Levels and Pulmonary Function Tests in Patients with Pulmonary Hypertension
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Lesley Ann Saketkoo, R.M. Hoffman, W. Dean, Shigeki Saito, A. Van, C.R. Hill, Bennett P. deBoisblanc, and Matthew R. Lammi
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medicine.medical_specialty ,Race (biology) ,business.industry ,Internal medicine ,medicine ,Cardiology ,In patient ,business ,medicine.disease ,Pulmonary hypertension ,Pulmonary function testing - Published
- 2019
15. Association Between Tobacco Smoking, Lung Function, Echocardiography, and Hemodynamics in Patients with Pulmonary Hypertension
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Shigeki Saito, C.R. Hill, R.M. Hoffman, A. Van, W. Dean, Lesley Ann Saketkoo, Matthew R. Lammi, S.P. Kantrow, and Bennett P. deBoisblanc
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medicine.medical_specialty ,business.industry ,Internal medicine ,medicine ,Cardiology ,Hemodynamics ,In patient ,business ,medicine.disease ,Pulmonary hypertension ,Lung function - Published
- 2019
16. Use of red cell distribution width in a population at high risk for pulmonary hypertension
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Thomas Kazecki, Matthew R. Lammi, Shigeki Saito, Laura A. Petrauskas, Vijay Jaligam, Bennett P. deBoisblanc, and Lesley Ann Saketkoo
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Pulmonary and Respiratory Medicine ,Adult ,Erythrocyte Indices ,Male ,medicine.medical_specialty ,Hypertension, Pulmonary ,Population ,Disease ,Gastroenterology ,World health ,Article ,Risk Factors ,Internal medicine ,Medicine ,Humans ,education ,Aged ,Retrospective Studies ,education.field_of_study ,Scleroderma, Systemic ,business.industry ,Red blood cell distribution width ,Middle Aged ,medicine.disease ,Pulmonary hypertension ,Cross-Sectional Studies ,Cohort ,Biomarker (medicine) ,Female ,Analysis of variance ,business ,Biomarkers - Abstract
BACKGROUND: Pulmonary hypertension (PH) often presents with non-specific symptoms making early diagnosis difficult. Red cell distribution width (RDW) is a parameter routinely reported on an automated complete blood cell count that has been associated with numerous disease states. The purpose of this study was to further evaluate RDW as a biomarker for PH in at-risk populations. METHODS: In a retrospective, cross-sectional analysis of patients seen at a PH center over 1 year, we examined both patients with PH and patients at risk for but without PH (e.g. systemic sclerosis, [SSc]). We also studied a group of age-and sex-matched, non-diseased controls. Relevant characteristics were compared among the 3 groups using one-way ANOVA. Similar comparisons were made across World Health Organization (WHO) PH groups 1–4. RESULTS: RDW was highest in the PH patients (n=181), intermediate in the at-risk for PH patients (n=52), and lowest in matched controls (n=100) (15.9±2.8 vs 14.8±2.8 vs 14.2±1.1%, respectively; p
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- 2019
17. Application of Artificial Intelligence to Automate Construction Materials Data Classification
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Shigeki Saito, Patai Padungtin, Kriengsak Panuwatwanich, Chayakrit Charoensiriwath, and Weerayut Chunyaem
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Computer science ,business.industry ,Data classification ,Artificial intelligence ,business - Published
- 2019
18. Inhibition of HDAC8 Ameliorates Pulmonary Fibrosis
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Joseph A. Lasky, Shigeki Saito, and Yan Zhuang
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Pathology ,medicine.medical_specialty ,business.industry ,Pulmonary fibrosis ,Genetics ,medicine ,HDAC8 ,medicine.disease ,business ,Molecular Biology ,Biochemistry ,Biotechnology - Published
- 2018
19. Comparison of the antifibrotic effects of the pan-histone deacetylase-inhibitor panobinostat versus the IPF-drug pirfenidone in fibroblasts from patients with idiopathic pulmonary fibrosis
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Walter Klepetko, Joseph A. Lasky, Andreas Guenther, Anna C. Bach, Werner Seeger, Clemens Ruppert, S Skwarna, D Stelmaszek, S Chillappagari, Poornima Mahavadi, Martina Korfei, Ludger Fink, Soni Savai Pullamsetti, Oliver H. Krämer, Shigeki Saito, and BreAnne MacKenzie
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0301 basic medicine ,Male ,Pulmonary Fibrosis ,lcsh:Medicine ,Gene Expression ,Apoptosis ,Biochemistry ,Histones ,Idiopathic pulmonary fibrosis ,chemistry.chemical_compound ,Fibrosis ,Animal Cells ,Pulmonary fibrosis ,Panobinostat ,Medicine and Health Sciences ,Post-Translational Modification ,Phosphorylation ,lcsh:Science ,Lung ,Connective Tissue Cells ,Extracellular Matrix Proteins ,Multidisciplinary ,Cell Death ,Histone deacetylase inhibitor ,Chemical Reactions ,Acetylation ,Pirfenidone ,respiratory system ,Middle Aged ,Endoplasmic Reticulum Stress ,Chemistry ,Connective Tissue ,Cell Processes ,Physical Sciences ,Female ,Cellular Types ,Anatomy ,medicine.drug ,Research Article ,STAT3 Transcription Factor ,medicine.drug_class ,Cell Survival ,Pyridones ,Primary Cell Culture ,Down-Regulation ,Protective Agents ,03 medical and health sciences ,DNA-binding proteins ,medicine ,Genetics ,Humans ,Cell Proliferation ,business.industry ,lcsh:R ,Biology and Life Sciences ,Proteins ,Cell Biology ,HDAC6 ,Fibroblasts ,medicine.disease ,Idiopathic Pulmonary Fibrosis ,respiratory tract diseases ,Histone Deacetylase Inhibitors ,030104 developmental biology ,Biological Tissue ,chemistry ,Cancer research ,lcsh:Q ,Histone deacetylase ,business ,Developmental Biology - Abstract
Background Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease with a poor prognosis. Pirfenidone is the first antifibrotic agent to be approved for IPF-treatment as it is able to slow down disease progression. However, there is no curative treatment other than lung transplantation. Because epigenetic alterations are associated with IPF, histone deacetylase (HDAC)-inhibitors have recently been proven to attenuate fibrotic remodeling in vitro and in vivo. This study compared the effects of pirfenidone with the pan-HDAC-inhibitor panobinostat/LBH589, a FDA-approved drug for the treatment of multiple myeloma, head-to-head on survival, fibrotic activity and proliferation of primary IPF-fibroblasts in vitro. Methods Primary fibroblasts from six IPF-patients were incubated for 24h with vehicle (0.25% DMSO), panobinostat (LBH589, 85 nM) or pirfenidone (2.7 mM), followed by assessment of proliferation and expression analyses for profibrotic and anti-apoptosis genes, as well as for ER stress and apoptosis-markers. In addition, the expression status of all HDAC enzymes was examined. Results Treatment of IPF-fibroblasts with panobinostat or pirfenidone resulted in a downregulated expression of various extracellular matrix (ECM)-associated genes, as compared to vehicle-treated cells. In agreement, both drugs decreased protein level of phosphorylated (p)-STAT3, a transcription factor mediating profibrotic responses, in treated IPF-fibroblasts. Further, an increase in histone acetylation was observed in response to both treatments, but was much more pronounced and excessive in panobinostat-treated IPF-fibroblasts. Panobinostat, but not pirfenidone, led to a significant suppression of proliferation in IPF-fibroblasts, as indicated by WST1- and BrdU assay and markedly diminished levels of cyclin-D1 and p-histone H3. Furthermore, panobinostat-treatment enhanced α-tubulin-acetylation, decreased the expression of survival-related genes Bcl-XL and BIRC5/survivin, and was associated with induction of ER stress and apoptosis in IPF-fibroblasts. In contrast, pirfenidone-treatment maintained Bcl-XL expression, and was neither associated with ER stress-induction nor any apoptotic signaling. Pirfenidone also led to increased expression of HDAC6 and sirtuin-2, and enhanced α-tubulin-deacetylation. But in line with its ability to increase histone acetylation, pirfenidone reduced the expression of HDAC enzymes HDAC1, -2 and -9. Conclusions We conclude that, beside other antifibrotic mechanisms, pirfenidone reduces profibrotic signaling also through STAT3 inactivation and weak epigenetic alterations in IPF-fibroblasts, and permits survival of (altered) fibroblasts. The pan-HDAC-inhibitor panobinostat reduces profibrotic phenotypes while inducing cell cycle arrest and apoptosis in IPF-fibroblasts, thus indicating more efficiency than pirfenidone in inactivating IPF-fibroblasts. We therefore believe that HDAC-inhibitors such as panobinostat can present a novel therapeutic strategy for IPF.
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- 2018
20. Ethnic differences in idiopathic pulmonary fibrosis: The Japanese perspective
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Koichi Hagiwara, Joseph A. Lasky, Y. Kondoh, and Shigeki Saito
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Pulmonary and Respiratory Medicine ,Male ,medicine.medical_specialty ,ARDS ,Lung Neoplasms ,Exacerbation ,Ethnic group ,behavioral disciplines and activities ,03 medical and health sciences ,Idiopathic pulmonary fibrosis ,0302 clinical medicine ,Gefitinib ,Sex Factors ,Asian People ,Japan ,Internal medicine ,Cause of Death ,medicine ,Prevalence ,Humans ,Genetic Predisposition to Disease ,030212 general & internal medicine ,Pneumonectomy ,Idiopathic interstitial pneumonia ,Protein Kinase Inhibitors ,Cause of death ,business.industry ,Interstitial lung disease ,respiratory system ,medicine.disease ,Prognosis ,Idiopathic Pulmonary Fibrosis ,respiratory tract diseases ,body regions ,Survival Rate ,030228 respiratory system ,Disease Progression ,Quinazolines ,Female ,business ,medicine.drug - Abstract
Epidemiologic data suggest that there are ethnic differences between Japanese and other populations with regard to the important clinical aspects of interstitial lung disease (ILD), such as the cause of death and prognostic factors in patients with idiopathic pulmonary fibrosis (IPF). Acute exacerbation (AE) of IPF may be more common in Japan than in the rest of the world, although this suggestion remains controversial. Moreover, AE of ILD induced by gefitinib may also be more common in Japan, indicating that Japanese patients have a genetic vulnerability or susceptibility to AE. Recent large-scale studies are starting to reveal ethnic differences in the genetics of ILD, including the prevalence of the genetic polymorphisms associated with the clinical course of ILD. We anticipate that ongoing and upcoming research regarding ethnic differences will continue to provide valuable insights into the pathogenesis and management of ILD.
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- 2017
21. Aberrant expression and activity of histone deacetylases in sporadic idiopathic pulmonary fibrosis
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Oliver H. Krämer, Daniel von der Beck, Clemens Ruppert, Shigeki Saito, Andreas Guenther, Poornima Mahavadi, Saverio Bellusci, BreAnne MacKenzie, Werner Seeger, S Skwarna, O Klymenko, Martina Korfei, Walter Klepetko, Ludger Fink, Ingrid Henneke, Bruno Crestani, and Soni Savai Pullamsetti
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Male ,Pulmonary and Respiratory Medicine ,Pathology ,medicine.medical_specialty ,Histone Deacetylase 2 ,Real-Time Polymerase Chain Reaction ,Histone Deacetylases ,Extracellular matrix ,Idiopathic pulmonary fibrosis ,medicine ,Humans ,Fibroblast ,Cells, Cultured ,business.industry ,Histone deacetylase 2 ,Interstitial lung disease ,Fibroblasts ,Middle Aged ,respiratory system ,medicine.disease ,HDAC3 ,HDAC4 ,Idiopathic Pulmonary Fibrosis ,respiratory tract diseases ,medicine.anatomical_structure ,Gene Expression Regulation ,RNA ,Female ,business ,Myofibroblast - Abstract
Background Activation and differentiation of fibroblasts into contractile protein-expressing myofibroblasts and their acquired apoptosis-resistant phenotype are critical factors towards the development of idiopathic pulmonary fibrosis (IPF), a fatal disease characterised by distorted pulmonary structure and excessive extracellular matrix (ECM) deposition. The molecular mechanisms underlying these processes in IPF remain incompletely understood. We investigated the possible implication of aberrant overexpression and activity of histone deacetylases (HDACs) in IPF. Methods We analysed lung tissues from patients with sporadic IPF (n=26) and non-diseased control lungs (n=16) for expression of class I and II HDACs. Primary IPF fibroblasts were treated with HDAC inhibitors (HDACi) LBH589 or valproic acid (VPA). Results Compared to control lungs, protein levels of class I (HDAC1, HDAC2, HDAC3, HDAC8) and class II HDACs (HDAC4, HDAC 5, HDAC 7, HDAC 9) were significantly elevated in IPF lungs. Using immunohistochemistry, strong induction of nearly all HDAC enzymes was observed in myofibroblasts of fibroblast foci and in abnormal bronchiolar basal cells at sites of aberrant re-epithelialisation in IPF lungs, but not in controls. Treatment of primary IPF fibroblasts with the pan-HDACi LBH589 resulted in significantly reduced expression of genes associated with ECM synthesis, proliferation and cell survival, as well as in suppression of HDAC7, and was paralleled by induction of endoplasmic reticulum stress and apoptosis. The profibrotic and apoptosis-resistant phenotype of IPF fibroblasts was also partly attenuated by the class I HDACi VPA. Conclusions Aberrant overexpression of HDACs in basal cells of IPF lungs may contribute to the bronchiolisation process in this disease. Similarly, generation and apoptosis resistance of IPF fibroblasts are mediated by enhanced activity of HDAC enzymes. Therefore, pan-HDAC inhibition by LBH589 may present a novel therapeutic option for patients with IPF.
- Published
- 2015
22. A multinational, open-label, phase 2 study of ruxolitinib in Asian patients with myelofibrosis: Japanese subset analysis
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Shinichiro Okamoto, Koichi Akashi, Taro Amagasaki, Shigeki Saito, Tetsuzo Tauchi, Kohshi Ohishi, Katsuto Takenaka, Kenji Oritani, Hiroshi Handa, Prashanth Gopalakrishna, and Kazuo Ito
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Adult ,Male ,Subset Analysis ,medicine.medical_specialty ,Ruxolitinib ,Anemia ,Phases of clinical research ,Gastroenterology ,Asian People ,Internal medicine ,Nitriles ,medicine ,Humans ,Adverse effect ,Myelofibrosis ,Protein Kinase Inhibitors ,Aged ,Janus Kinases ,Aged, 80 and over ,Hematology ,business.industry ,Middle Aged ,medicine.disease ,Surgery ,Clinical trial ,Pyrimidines ,Treatment Outcome ,Primary Myelofibrosis ,Pyrazoles ,Female ,business ,Spleen ,medicine.drug - Abstract
Ruxolitinib is a potent Janus kinase (JAK) 1/JAK2 inhibitor that has demonstrated rapid and durable improvements in splenomegaly and symptoms and a survival benefit in 2 phase 3 trials in patients with myelofibrosis. Ruxolitinib was well tolerated and effectively reduced splenomegaly and symptom burden in Asian patients with myelofibrosis in the Asian multinational, phase 2 Study A2202. We present a subset analysis of Japanese patients (n = 30) in Study A2202. At data cutoff, 22 patients were ongoing; 8 discontinued, mainly due to adverse events (n = 4). At week 24, 33 % of patients achieved ≥35 % reduction from baseline in spleen volume; 56.0 % achieved ≥50 % reduction from baseline in total symptom score, as measured by the 7-day Myelofibrosis Symptom Assessment Form v2.0. The most common adverse events were anemia (63 %), thrombocytopenia (40 %), nasopharyngitis (37 %), decreased platelet counts (30 %), and diarrhea (30 %). Dose reductions or interruptions due to hemoglobin decreases were more frequent in Japanese patients; no loss of efficacy and no discontinuations due to hematologic abnormalities were observed. Ruxolitinib was well tolerated in Japanese patients and provided substantial reductions in splenomegaly and myelofibrosis-related symptoms similar to those observed in the overall Asian population and phase 3 COMFORT studies.
- Published
- 2015
23. Transcutaneous Xenon Light Irradiation Around the Stellate Ganglion Increases Skeletal Muscle Blood flow in the Upper Extremity
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Nanako Sato, Yui Sato, Kimihiro Sato, Takaya Maeda, Shigeki Saito, and Hideki Yoshida
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medicine.anatomical_structure ,Xenon ,chemistry ,business.industry ,Stellate ganglion ,medicine ,Skeletal muscle blood flow ,Light irradiation ,chemistry.chemical_element ,Physical Therapy, Sports Therapy and Rehabilitation ,Anatomy ,business - Published
- 2015
24. Efficacy and safety of ruxolitinib in Asian patients with myelofibrosis
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Yu Hu, Ming Hou, Hiroshi Handa, Seonyang Park, Ki Seong Eom, Taro Amagasaki, Kazuo Ito, Shigeki Saito, Wu Depei, Kohshi Ohishi, Xin Du, Tetsuzo Tauchi, Zhijian Xiao, Kenji Oritani, Junmin Li, Ming Chung Wang, Katsuto Takenaka, Chul Won Jung, Li Jianyong, Koichi Akashi, Shinichiro Okamoto, Jin Jie, Daobin Zhou, Jin Seok Kim, Hsin-An Hou, Lee Yung Shih, Prashanth Gopalakrishna, and Ting Liu
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Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Ruxolitinib ,Constitutional symptoms ,Bone marrow fibrosis ,Symptom assessment ,Placebo ,Asian People ,Internal medicine ,Nitriles ,medicine ,Clinical endpoint ,Humans ,Myelofibrosis ,Adverse effect ,Protein Kinase Inhibitors ,Aged ,Neoplasm Staging ,Aged, 80 and over ,business.industry ,Janus Kinase 1 ,Hematology ,Janus Kinase 2 ,Middle Aged ,Prognosis ,medicine.disease ,Surgery ,Pyrimidines ,Oncology ,Primary Myelofibrosis ,Quality of Life ,Pyrazoles ,Female ,business ,Follow-Up Studies ,medicine.drug - Abstract
Myelofibrosis is characterized by progressive cytopenias, bone marrow fibrosis, splenomegaly and severe constitutional symptoms. In the phase 3 Controlled Myelofibrosis Study with Oral JAK Inhibitor Treatment (COMFORT) studies, ruxolitinib, a potent Janus kinase 1 (JAK1)/JAK2 inhibitor, provided substantial improvements in splenomegaly, symptoms, quality-of-life measures and overall survival compared with placebo or best available therapy. No assessments of the efficacy and safety of ruxolitinib have been conducted in Asian patients. Here, we describe results from an open-label, single-arm, phase 2 trial evaluating ruxolitinib in Asian patients with myelofibrosis (n = 120). The primary endpoint was met, with 31.7% of patients achieving a ≥ 35% reduction from baseline spleen volume at week 24. As measured by the 7-day Myelofibrosis Symptom Assessment Form v2.0, 49% of patients achieved a ≥ 50% reduction from baseline in total symptom score. Adverse events were consistent with those seen in the COMFORT studies. Ruxolitinib was well tolerated in Asian patients with myelofibrosis and provided substantial reductions in splenomegaly and improvements in symptoms.
- Published
- 2014
25. Evaluation of the dose and efficacy of ruxolitinib in Japanese patients with myelofibrosis
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Kenji Oritani, Hikaru Okada, Hiroshi Handa, Katsuto Takenaka, Keita Kirito, Kazuyuki Suzuki, Shinichiro Okamoto, Toshio Yonezu, Shigeki Saito, Taro Amagasaki, Koichi Akashi, Kazuya Shimoda, Norio Komatsu, Tetsuzo Tauchi, and Kohshi Ohishi
- Subjects
Adult ,Male ,medicine.medical_specialty ,Ruxolitinib ,Spleen ,Placebo ,Drug Administration Schedule ,03 medical and health sciences ,0302 clinical medicine ,Asian People ,Internal medicine ,Nitriles ,medicine ,Effective treatment ,Humans ,Janus Kinase Inhibitors ,Multicenter Studies as Topic ,Symptom control ,Myelofibrosis ,Adverse effect ,Aged ,Aged, 80 and over ,Hematology ,Clinical Trials, Phase I as Topic ,Dose-Response Relationship, Drug ,business.industry ,Clinical Studies as Topic ,Middle Aged ,medicine.disease ,Surgery ,medicine.anatomical_structure ,Pyrimidines ,Treatment Outcome ,Clinical Trials, Phase III as Topic ,Primary Myelofibrosis ,030220 oncology & carcinogenesis ,Pyrazoles ,Female ,business ,030215 immunology ,medicine.drug - Abstract
Ruxolitinib, a potent JAK1/JAK2 inhibitor, improved splenomegaly and myelofibrosis-associated symptoms and prolonged survival compared with placebo and best available therapy in the phase 3 COMFORT studies. Although cytopenias were the most common adverse events associated with ruxolitinib treatment, a COMFORT-I analysis showed that they were managed effectively with dose modifications, without a negative impact on the efficacy of ruxolitinib. Subsequently, studies A2202 and AJP01 showed that ruxolitinib is an effective treatment for Japanese patients with myelofibrosis. We conducted a pooled analysis of these two studies (N = 81) to evaluate the association between ruxolitinib dose and changes in spleen volume or symptoms in Japanese patients. Most patients began treatment at 15 or 20 mg twice daily (BID); 70% received a final titrated dose ≥ 10 mg BID. Overall, 91% of patients exhibited spleen volume reductions; patients with final titrated doses ≥ 10 mg BID had larger spleen volume reductions. Similarly, 83% of patients showed improvements in symptom scores; those with a final titrated dose of 20 or 25 mg BID had the greatest reductions. Consistent with COMFORT-I, this pooled analysis indicates that, despite dose adjustments, ruxolitinib provides spleen and symptom control in Japanese patients, with higher doses associated with better responses.
- Published
- 2017
26. Tubastatin ameliorates pulmonary fibrosis by targeting the TGFβ-PI3K-Akt pathway
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Yan Zhuang, Shigeki Saito, Martina Korfei, Bin Shan, Fayong Luo, Andreas Guenther, Svitlana Danchuk, and Joseph A. Lasky
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Male ,Protein Expression ,mTORC1 ,Biochemistry ,Idiopathic pulmonary fibrosis ,Transforming Growth Factor beta ,Animal Cells ,Pulmonary fibrosis ,Phosphoprotein Phosphatases ,Medicine ,lcsh:Science ,Lung ,Connective Tissue Cells ,Aged, 80 and over ,TOR Serine-Threonine Kinases ,Chemical Reactions ,3. Good health ,Physical Sciences ,Cellular Types ,Molecular Probe Techniques ,Bleomycin ,03 medical and health sciences ,Humans ,RNA, Messenger ,Molecular Biology Techniques ,Molecular Biology ,Aged ,Molecular Biology Assays and Analysis Techniques ,Ribosomal Protein S6 Kinases ,lcsh:R ,Biology and Life Sciences ,Proteins ,Fibroblasts ,medicine.disease ,respiratory tract diseases ,Biological Tissue ,030104 developmental biology ,chemistry ,Multiprotein Complexes ,lcsh:Q ,Developmental Biology ,Vascular Endothelial Growth Factor A ,0301 basic medicine ,Indoles ,Pulmonary Fibrosis ,lcsh:Medicine ,Histone Deacetylase 6 ,Hydroxamic Acids ,Phosphatidylinositol 3-Kinases ,chemistry.chemical_compound ,Tubulin ,Medicine and Health Sciences ,Phosphorylation ,Post-Translational Modification ,Mice, Knockout ,Multidisciplinary ,Cell Death ,biology ,Nuclear Proteins ,Acetylation ,Animal Models ,Middle Aged ,respiratory system ,Chemistry ,medicine.anatomical_structure ,Experimental Organism Systems ,Connective Tissue ,Cell Processes ,Female ,Anatomy ,Signal Transduction ,Research Article ,Autophagic Cell Death ,Immunoblotting ,Mouse Models ,Mechanistic Target of Rapamycin Complex 1 ,Research and Analysis Methods ,Collagen Type I ,Histone Deacetylases ,Model Organisms ,Autophagy ,Gene Expression and Vector Techniques ,Animals ,PI3K/AKT/mTOR pathway ,business.industry ,Autophagosomes ,Cell Biology ,Transforming growth factor beta ,HDAC6 ,Hypoxia-Inducible Factor 1, alpha Subunit ,Fibrosis ,Idiopathic Pulmonary Fibrosis ,biology.protein ,Cancer research ,business ,Proto-Oncogene Proteins c-akt ,Collagens - Abstract
Background Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal disease. Histone deacetylase 6 (HDAC6) alters function and fate of various proteins via deacetylation of lysine residues, and is implicated in TGF-β1-induced EMT (epithelial-mesenchymal transition). However, the role of HDAC6 in pulmonary fibrosis is unknown. Methods HDAC6 expression in IPF and control lungs was assessed by quantitative real-time PCR (qRT-PCR) and immunoblots. Lung fibroblasts were treated with TGF-β1 ± HDAC6 inhibitors (Tubacin, Tubastatin, ACY1215, or MC1568), and fibrotic markers such as type I collagen were assessed using qRT-PCR and immunoblots. Mice were treated with bleomycin (oropharyngeal aspiration; single dose) ± Tubastatin (intraperitoneally injection; daily for 21 days), and lung collagen expression was gauged using immunoblots and trichrome staining. In a separate experiment, HDAC6 wild-type (WT) and knockout (KO) mice were administered bleomycin, and lungs were evaluated in the same manner. Results HDAC6 expression was deregulated in IPF lungs. Among the HDAC6 inhibitors tested, only Tubastatin significantly repressed TGF-β1-induced expression of type-1 collagen in lung fibroblasts, and this finding was coupled with decreased Akt phosphorylation and increased Akt-PHLPP (PH domain and Leucine rich repeat Protein Phosphatase) association. Tubastatin repressed TGF-β1-induced S6K phosphorylation, HIF-1α expression, and VEGF expression. Tubastatin also repressed TGF-β1-induced inhibition of LC3B-II (a marker of autophagosome formation). In bleomycin-treated mouse lungs, HDAC6 expression was increased, and Tubastatin repressed type-1 collagen expression. However, in HDAC6 KO mice, bleomycin-induced type-1 collagen expression was not repressed compared to WT mice. Knockdown of HDAC6, as well as HDAC10, another potential Tubastatin target, did not inhibit TGF-β1-induced collagen expression in lung fibroblasts. Conclusions HDAC6 expression is altered during lung fibrogenesis. Tubastatin represses TGF-β1-induced collagen expression, by diminishing Akt phosphorylation and regulating downstream targets such as HIF-1α-VEGF axis and autophagy. Tubastatin-treated WT mice are protected against bleomycin-induced fibrosis, but HDAC6 KO mice are not. Our data suggest that Tubastatin ameliorates pulmonary fibrosis, by targeting the TGFβ-PI3K-Akt pathway, likely via an HDAC6-independent mechanism.
- Published
- 2017
27. Development of a bipolar electrostatic chuck module with a beam-array assembly using the multiple etching process
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Shigeki Saito, Seungman Choi, Kazuki Wakabayashi, and Kunio Takahashi
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010302 applied physics ,Materials science ,business.industry ,Mechanical Engineering ,Process (computing) ,02 engineering and technology ,021001 nanoscience & nanotechnology ,01 natural sciences ,Electronic, Optical and Magnetic Materials ,Mechanics of Materials ,Etching (microfabrication) ,0103 physical sciences ,Optoelectronics ,Development (differential geometry) ,Electrical and Electronic Engineering ,0210 nano-technology ,business ,Beam (structure) - Published
- 2018
28. Development of Adult T-cell Leukemia in a Patient with Rheumatoid Arthritis Treated with Tocilizumab
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Takahisa Suzuki, Katsumi Eguchi, Atsushi Kawakami, Tomoki Naoe, Shigeki Saito, Yukitaka Ueki, Hideki Nakamura, and Yoshiro Horai
- Subjects
musculoskeletal diseases ,medicine.medical_specialty ,Exacerbation ,T-cell leukemia ,Adult T-cell leukemia ,Antibodies, Monoclonal, Humanized ,Gastroenterology ,Arthritis, Rheumatoid ,chemistry.chemical_compound ,Tocilizumab ,Refractory ,immune system diseases ,Internal medicine ,hemic and lymphatic diseases ,Internal Medicine ,medicine ,Humans ,Leukemia-Lymphoma, Adult T-Cell ,Rheumatoid arthritis ,skin and connective tissue diseases ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,Clinical trial ,Leukemia ,Treatment Outcome ,chemistry ,Immunology ,Methotrexate ,Female ,business ,medicine.drug - Abstract
Tocilizumab (TCZ) was administered from 2004 to 2008 in a 52-year-old woman with rheumatoid arthritis (RA) refractory to methotrexate (MTX) as a clinical trial. TCZ therapy with MTX was resumed in March 2009 due to exacerbation of RA. The patient was an human T-lymphotropic virus type I (HTLV-I) carrier, and, in April 2011, a peripheral blood smear showed many atypical lymphocytes, thus leading to a diagnosis of adult T-cell leukemia (ATL). Complete remission of ATL was achieved with a standard therapeutic regimen., Internal Medicine, 52(17), pp.1983-1986; 2013
- Published
- 2013
29. Global initiative for meticillin-resistant Staphylococcus aureus pneumonia (GLIMP): an international, observational cohort study
- Author
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Stefano Aliberti, Luis F Reyes, Paola Faverio, Giovanni Sotgiu, Simone Dore, Alejandro H Rodriguez, Nilam J Soni, Marcos I Restrepo, Patricia Karina Aruj, Silvia Attorri, Enrique Barimboim, Juan Pablo Caeiro, María I Garzón, Victor Hugo Cambursano, Adrian Ceccato, Julio Chertcoff, Florencia Lascar, Fernando Di Tulio, Ariel Cordon Díaz, Lautaro de Vedia, Maria Cristina Ganaha, Sandra Lambert, Gustavo Lopardo, Carlos M Luna, Alessio Gerardo Malberti, Nora Morcillo, Silvina Tartara, Claudia Pensotti, Betiana Pereyra, Pablo Gustavo Scapellato, Juan Pablo Stagnaro, Sonali Shah, Felix Lötsch, Florian Thalhammer, Jean Louis Vincent, Kurt Anseeuw, Camille A Francois, Eva Van Braeckel, Marcel Zannou Djimon, Jules Bashi, Roger Dodo, Simone Aranha Nouér, Peter Chipev, Milena Encheva, Darina Miteva, Diana Petkova, Adamou Dodo Balkissou, Eric Walter Pefura Yone, Bertrand Hugo Mbatchou Ngahane, Ning Shen, Jin-fu Xu, Carlos Andres Bustamante Rico, Ricardo Buitrago, Fernando Jose Pereira Paternina, Jean-Marie Kayembe Ntumba, Vesna Vladic Carevic, Marko Jakopovic, Mateja Jankovic, Zinka Matkovic, Ivan Mitrecic, Marie-Laure Bouchy Jacobsson, Anette Bro Christensen, Uffe Christian Heitmann Bødtger, Christian Niels Meyer, Andreas Vestergaard Jensen, Gertrud Baunbæk-knudsen, Pelle Trier Petersen, Stine Andersen, Ibrahim El-Said Abd El-Wahhab, Nesreen Elsayed Morsy, Hanaa Shafiek, Eman Sobh, Kedir Abdella Abdulsemed, Fabrice Bertrand, Christian Brun-Buisson, Etienne de Montmollin, Muriel Fartoukh, Jonathan Messika, Pierre Tattevin, Abdo Khoury, Bernard Ebruke, Michael Dreher, Martin Kolditz, Matthias Meisinger, Mathias W Pletz, Stefan Hagel, Jan Rupp, Tom Schaberg, Marc Spielmanns, Petra Creutz, Norton Suttorp, Beatrice Siaw-Lartey, Katerina Dimakou, Dimosthenis Papapetrou, Evdoxia Tsigou, Dimitrios Ampazis, Evangelos Kaimakamis, Mohit Bhatia, Raja Dhar, George D'Souza, Rajiv Garg, Parvaiz A Koul, P A Mahesh, B S Jayaraj, Kiran Vishnu Narayan, Hirennappa B Udnur, Shashi Bhaskara Krishnamurthy, Surya Kant, Rajesh Swarnakar, Sneha Limaye, Sundeep Salvi, Keihan Golshani, Vera M Keatings, Ignacio Martin-Loeches, Yasmin Maor, Jacob Strahilevitz, Salvatore Battaglia, Maria Carrabba, Piero Ceriana, Marco Confalonieri, Antonella d'Arminio Monforte, Bruno Del Prato, Marino De Rosa, Riccardo Fantini, Giuseppe Fiorentino, Maria Antonia Gammino, Francesco Menzella, Giuseppe Milani, Stefano Nava, Gerardo Palmiero, Roberta Petrino, Barbra Gabrielli, Paolo Rossi, Claudio Sorino, Gundi Steinhilber, Alessandro Zanforlin, Fabio Franzetti, Manuela Carugati, Manuela Morosi, Elisa Monge, Mauro Carone, Vincenzo Patella, Simone Scarlata, Andrea Comel, Kiyoyasu Kurahashi, Zeina Aoun Bacha, Daniel Barajas Ugalde, Omar Ceballos Zuñiga, José F Villegas, Milic Medenica, E M W van de Garde, Deebya Raj Mihsra, Poojan Shrestha, Elliott Ridgeon, Babatunde Ishola Awokola, Ogonna N O Nwankwo, Adefuye Bolanle Olufunlola, Segaolu Olumide, Kingsley N Ukwaja, Muhammad Irfan, Lukasz Minarowski, Skoczynski Szymon, Felipe Froes, Pedro Leuschner, Mariana Meireles, Cláudia Ferrão, João Neves, Sofia B Ravara, Victoria Brocovschii, Chesov Ion, Doina Rusu, Cristina Toma, Daniela Chirita, Carmen Mihaela Dorobat, Alexei Birkun, Anna Kaluzhenina, Abdullah Almotairi, Zakeya Abdulbaqi Ali Bukhary, Jameela Edathodu, Amal Fathy, Abdullah Mushira Abdulaziz Enani, Nazik Eltayeb Mohamed, Jawed Ulhadi Memon, Abdelhaleem Bella, Nada Bogdanovic, Branislava Milenkovic, Dragica Pesut, Luis Borderìas, Noel Manuel Bordon Garcia, Hugo Cabello Alarcón, Catia Cilloniz, Antoni Torres, Vicens Diaz-Brito, Xavier Casas, Alicia Encabo González, Maria Luisa Fernández-Almira, Miguel Gallego, Inmaculada Gaspar-GarcÍa, Juan González del Castillo, Patricia Javaloyes Victoria, Elena Laserna Martínez, Rosa Malo de Molina, Pedro J Marcos, Rosario Menéndez, Ana Pando-Sandoval, Cristina Prat Aymerich, Alicia Lacoma de la Torre, Ignasi García-Olivé, Jordi Rello, Silvia Moyano, Francisco Sanz, Oriol Sibila, Ana Rodrigo-Troyano, Jordi Solé-Violán, Ane Uranga, Job FM van Boven, Ester Vendrell Torra, Jordi Almirall Pujol, Charles Feldman, Ho Kee Yum, Arnauld Attannon Fiogbe, Ferdaous Yangui, Semra Bilaceroglu, Levent Dalar, Ufuk Yilmaz, Artemii Bogomolov, Naheed Elahi, Devesh J Dhasmana, Andrew Feneley, Rhiannon Ions, Julie Skeemer, Gerrit Woltmann, Carole Hancock, Adam T Hill, Banu Rudran, Silvia Ruiz-Buitrago, Marion Campbell, Paul Whitaker, Alexander Youzguin, Anika Singanayagam, Karen S Allen, Veronica Brito, Jessica Dietz, Claire E Dysart, Susan M Kellie, Ricardo A Franco-Sadud, Garnet Meier, Mina Gaga, Thomas L Holland, Stephen P Bergin, Fayez Kheir, Mark Landmeier, Manuel Lois, Girish B Nair, Hemali Patel, Katherine Reyes, William Rodriguez-Cintron, Shigeki Saito, Julio Noda, Cecilia I Hinojosa, Stephanie M Levine, Luis F Angel, Antonio Anzueto, K Scott Whitlow, John Hipskind, Kunal Sukhija, Vicken Totten, Richard G Wunderink, Ray D Shah, Kondwelani John Mateyo, Lorena Noriega, Ezequiel Alvarado, Mohamed Aman, Lucía Labra, Aliberti, S., Reyes, L. F., Faverio, P., Sotgiu, G., Dore, S., Rodriguez, A. H., Soni, N. J., Restrepo, M. I., Aruj, P. K., Attorri, S., Barimboim, E., Caeiro, J. P., Garzon, M. I., Cambursano, Vh., Ceccato, A., Chertcoff, J., Lascar, F., Di Tulio, F., Cordon Diaz, A., de Vedia, L., Ganaha, M. C., Lambert, S., Lopardo, G., Luna, C. M., Malberti, A. G., Morcillo, N., Tartara, S., Pensotti, C., Pereyra, B., Scapellato, P. G., Stagnaro, J. P., Shah, S., Lotsch, F., Thalhammer, F., Vincent, J. L., Anseeuw, K., Francois, C. A., Van Braeckel, E., Djimon, M. Z., Bashi, J., Dodo, R., Aranha Nouer, S., Chipev, P., Encheva, M., Miteva, D., Petkova, D., Balkissou, A. D., Pefura Yone, E. W., Mbatchou Ngahane, B. H., Shen, N., Xu, J. F., Bustamante Rico, C. A., Buitrago, R., Pereira Paternina, F. J., Kayembe Ntumba, J. M., Vladic Carevic, V., Jakopovic, M., Jankovic, M., Matkovic, Z., Mitrecic, I., Bouchy Jacobsson, M. L., Bro Christensen, A., Heitmann Bodtger, U. C., Meyer, C. N., Vestergaard Jensen, A., Baunbaek-Knudsen, G., Trier Petersen, P., Andersen, S., El-Said Abd El-Wahhab, I., Elsayed Morsy, N., Shafiek, H., Sobh, E., Abdulsemed, K. A., Bertrand, F., Brun-Buisson, C., de Montmollin, E., Fartoukh, M., Messika, J., Tattevin, P., Khoury, A., Ebruke, B., Dreher, M., Kolditz, M., Meisinger, M., Pletz, M. W., Hagel, S., Rupp, J., Schaberg, T., Spielmanns, M., Creutz, P., Suttorp, N., Siaw-Lartey, B., Dimakou, K., Papapetrou, D., Tsigou, E., Ampazis, D., Kaimakamis, E., Bhatia, M., Dhar, R., D'Souza, G., Garg, R., Koul, P. A., Mahesh, P. A., Jayaraj, B. S., Narayan, K. V., Udnur, H. B., Krishnamurthy, S. B., Kant, S., Swarnakar, R., Limaye, S., Salvi, S., Golshani, K., Keatings, V. M., Martin-Loeches, I., Maor, Y., Strahilevitz, J., Battaglia, S., Carrabba, M., Ceriana, P., Confalonieri, M., d'Arminio Monforte, A., Del Prato, B., De Rosa, M., Fantini, R., Fiorentino, G., Gammino, M. A., Menzella, F., Milani, G., Nava, S., Palmiero, G., Petrino, R., Gabrielli, B., Rossi, P., Sorino, C., Steinhilber, G., Zanforlin, A., Franzetti, F., Carugati, M., Morosi, M., Monge, E., Carone, M., Patella, V., Scarlata, S., Comel, A., Kurahashi, K., Aoun Bacha, Z., Barajas Ugalde, D., Ceballos Zuniga, O., Villegas, J. F., Medenica, M., van de Garde, Emw., Raj Mihsra, D., Shrestha, P., Ridgeon, E., Ishola Awokola, B., Nwankwo, Ono., Olufunlola, A. B., Olumide, S., Ukwaja, K. N., Irfan, M., Minarowski, L., Szymon, S., Froes, F., Leuschner, P., Meireles, M., Ferrao, C., Neves, J., Ravara, S. B., Brocovschii, V., Ion, C., Rusu, D., Toma, C., Chirita, D., Dorobat, C. M., Birkun, A., Kaluzhenina, A., Almotairi, A., Bukhary, Zaa., Edathodu, J., Fathy, A., Mushira Abdulaziz Enani, A., Eltayeb Mohamed, N., Ulhadi Memon, J., Bella, A., Bogdanovic, N., Milenkovic, B., Pesut, D., Borderias, L., Bordon Garcia, N. M., Cabello Alarcon, H., Cilloniz, C., Torres, A., Diaz-Brito, V., Casas, X., Encabo Gonzalez, A., Fernandez-Almira, M. L., Gallego, M., Gaspar-GarcIa, I., Gonzalez Del Castillo, J., Javaloyes Victoria, P., Laserna Martinez, E., Malo de Molina, R., Marcos, P. J., Menendez, R., Pando-Sandoval, A., Prat Aymerich, C., Lacoma de la Torre, A., Garcia-Olive, I., Rello, J., Moyano, S., Sanz, F., Sibila, O., Rodrigo-Troyano, A., Sole-Violan, J., Uranga, A., van Boven, J. F., Vendrell Torra, E., Pujol, J. A., Feldman, C., Kee Yum, H., Fiogbe, A. A., Yangui, F., Bilaceroglu, S., Dalar, L., Yilmaz, U., Bogomolov, A., Elahi, N., Dhasmana, D. J., Feneley, A., Ions, R., Skeemer, J., Woltmann, G., Hancock, C., Hill, A. T., Rudran, B., Ruiz-Buitrago, S., Campbell, M., Whitaker, P., Youzguin, A., Singanayagam, A., Allen, K. S., Brito, V., Dietz, J., Dysart, C. E., Kellie, S. M., Franco-Sadud, R. A., Meier, G., Gaga, M., Holland, T. L., Bergin, S. P., Kheir, F., Landmeier, M., Lois, M., Nair, G. B., Patel, H., Reyes, K., Rodriguez-Cintron, W., Saito, S., Noda, J., Hinojosa, C. I., Levine, S. M., Angel, L. F., Anzueto, A., Whitlow, K. S., Hipskind, J., Sukhija, K., Totten, V., Wunderink, R. G., Shah, R. D., Mateyo, K. J., Noriega, L., Alvarado, E., Aman, M., Labra, L., Aliberti S., Reyes L.F., Faverio P., Sotgiu G., Dore S., Rodriguez A.H., Soni N.J., Restrepo M.I., Aruj P.K., Attorri S., Barimboim E., Caeiro J.P., Garzon M.I., Cambursano VH., Ceccato A., Chertcoff J., Lascar F., Di Tulio F., Cordon Diaz A., de Vedia L., Ganaha M.C., Lambert S., Lopardo G., Luna C.M., Malberti A.G., Morcillo N., Tartara S., Pensotti C., Pereyra B., Scapellato P.G., Stagnaro J.P., Shah S., Lotsch F., Thalhammer F., Vincent J.L., Anseeuw K., Francois C.A., Van Braeckel E., Djimon M.Z., Bashi J., Dodo R., Aranha Nouer S., Chipev P., Encheva M., Miteva D., Petkova D., Balkissou A.D., Pefura Yone E.W., Mbatchou Ngahane B.H., Shen N., Xu J.F., Bustamante Rico C.A., Buitrago R., Pereira Paternina F.J., Kayembe Ntumba J.M., Vladic Carevic V., Jakopovic M., Jankovic M., Matkovic Z., Mitrecic I., Bouchy Jacobsson M.L., Bro Christensen A., Heitmann Bodtger U.C., Meyer C.N., Vestergaard Jensen A., Baunbaek-Knudsen G., Trier Petersen P., Andersen S., El-Said Abd El-Wahhab I., Elsayed Morsy N., Shafiek H., Sobh E., Abdulsemed K.A., Bertrand F., Brun-Buisson C., de Montmollin E., Fartoukh M., Messika J., Tattevin P., Khoury A., Ebruke B., Dreher M., Kolditz M., Meisinger M., Pletz M.W., Hagel S., Rupp J., Schaberg T., Spielmanns M., Creutz P., Suttorp N., Siaw-Lartey B., Dimakou K., Papapetrou D., Tsigou E., Ampazis D., Kaimakamis E., Bhatia M., Dhar R., D'Souza G., Garg R., Koul P.A., Mahesh P.A., Jayaraj B.S., Narayan K.V., Udnur H.B., Krishnamurthy S.B., Kant S., Swarnakar R., Limaye S., Salvi S., Golshani K., Keatings V.M., Martin-Loeches I., Maor Y., Strahilevitz J., Battaglia S., Carrabba M., Ceriana P., Confalonieri M., d'Arminio Monforte A., Del Prato B., De Rosa M., Fantini R., Fiorentino G., Gammino M.A., Menzella F., Milani G., Nava S., Palmiero G., Petrino R., Gabrielli B., Rossi P., Sorino C., Steinhilber G., Zanforlin A., Franzetti F., Carugati M., Morosi M., Monge E., Carone M., Patella V., Scarlata S., Comel A., Kurahashi K., Aoun Bacha Z., Barajas Ugalde D., Ceballos Zuniga O., Villegas J.F., Medenica M., van de Garde EMW., Raj Mihsra D., Shrestha P., Ridgeon E., Ishola Awokola B., Nwankwo ONO., Olufunlola A.B., Olumide S., Ukwaja K.N., Irfan M., Minarowski L., Szymon S., Froes F., Leuschner P., Meireles M., Ferrao C., Neves J., Ravara S.B., Brocovschii V., Ion C., Rusu D., Toma C., Chirita D., Dorobat C.M., Birkun A., Kaluzhenina A., Almotairi A., Bukhary ZAA., Edathodu J., Fathy A., Mushira Abdulaziz Enani A., Eltayeb Mohamed N., Ulhadi Memon J., Bella A., Bogdanovic N., Milenkovic B., Pesut D., Borderias L., Bordon Garcia N.M., Cabello Alarcon H., Cilloniz C., Torres A., Diaz-Brito V., Casas X., Encabo Gonzalez A., Fernandez-Almira M.L., Gallego M., Gaspar-GarcIa I., Gonzalez Del Castillo J., Javaloyes Victoria P., Laserna Martinez E., Malo de Molina R., Marcos P.J., Menendez R., Pando-Sandoval A., Prat Aymerich C., Lacoma de la Torre A., Garcia-Olive I., Rello J., Moyano S., Sanz F., Sibila O., Rodrigo-Troyano A., Sole-Violan J., Uranga A., van Boven J.F., Vendrell Torra E., Pujol J.A., Feldman C., Kee Yum H., Fiogbe A.A., Yangui F., Bilaceroglu S., Dalar L., Yilmaz U., Bogomolov A., Elahi N., Dhasmana D.J., Feneley A., Ions R., Skeemer J., Woltmann G., Hancock C., Hill A.T., Rudran B., Ruiz-Buitrago S., Campbell M., Whitaker P., Youzguin A., Singanayagam A., Allen K.S., Brito V., Dietz J., Dysart C.E., Kellie S.M., Franco-Sadud R.A., Meier G., Gaga M., Holland T.L., Bergin S.P., Kheir F., Landmeier M., Lois M., Nair G.B., Patel H., Reyes K., Rodriguez-Cintron W., Saito S., Noda J., Hinojosa C.I., Levine S.M., Angel L.F., Anzueto A., Whitlow K.S., Hipskind J., Sukhija K., Totten V., Wunderink R.G., Shah R.D., Mateyo K.J., Noriega L., Alvarado E., Aman M., Labra L., Aliberti, S, Reyes, L, Faverio, P, Sotgiu, G, Dore, S, Rodriguez, A, Soni, N, and Restrepo, M
- Subjects
Male ,antibiotic resistance ,Prevalence ,MRSA ,medicine.disease_cause ,pneumonia ,staphylococcus aureus ,Global Health ,Cohort Studies ,0302 clinical medicine ,Community-acquired pneumonia ,Risk Factors ,Retrospective Studie ,Community-Acquired Infection ,030212 general & internal medicine ,education.field_of_study ,Cross Infection ,Respiratory tract infections ,Methicillin-Resistant Staphylococcus aureu ,Staphylococcal Infections ,Hospitals ,Community-Acquired Infections ,Infectious Diseases ,Infectious diseases ,Female ,Human ,Methicillin-Resistant Staphylococcus aureus ,medicine.medical_specialty ,Population ,Admission ,staphylococcus aureu ,Settore MED/10 - Malattie Dell'Apparato Respiratorio ,03 medical and health sciences ,Hospital ,Internal medicine ,medicine ,Humans ,Risk factor ,education ,Intensive care medicine ,Staphylococcal Infection ,Retrospective Studies ,Aged ,business.industry ,Risk Factor ,Odds ratio ,Pneumonia ,medicine.disease ,Methicillin-resistant Staphylococcus aureus ,030228 respiratory system ,Methicillin Resistance ,Cohort Studie ,business - Abstract
BACKGROUND: Antibiotic resistance is a major global health problem and pathogens such as meticillin-resistant Staphylococcus aureus (MRSA) have become of particular concern in the management of lower respiratory tract infections. However, few data are available on the worldwide prevalence and risk factors for MRSA pneumonia. We aimed to determine the point prevalence of MRSA pneumonia and identify specific MRSA risk factors in community-dwelling patients hospitalised with pneumonia.METHODS: We did an international, multicentre study of community-dwelling, adult patients admitted to hospital with pneumonia who had microbiological tests taken within 24 h of presentation. We recruited investigators from 222 hospitals in 54 countries to gather point-prevalence data for all patients admitted with these characteristics during 4 days randomly selected during the months of March, April, May, and June in 2015. We assessed prevalence of MRSA pneumonia and associated risk factors through logistic regression analysis.FINDINGS: 3702 patients hospitalised with pneumonia were enrolled, with 3193 patients receiving microbiological tests within 24 h of admission, forming the patient population. 1173 (37%) had at least one pathogen isolated (culture-positive population). The overall prevalence of confirmed MRSA pneumonia was 3·0% (n=95), with differing prevalence between continents and countries. Three risk factors were independently associated with MRSA pneumonia: previous MRSA infection or colonisation (odds ratio 6·21, 95% CI 3·25-11·85), recurrent skin infections (2·87, 1·10-7·45), and severe pneumonia disease (2·39, 1·55-3·68).INTERPRETATION: This multicountry study shows low prevalence of MRSA pneumonia and specific MRSA risk factors among community-dwelling patients hospitalised with pneumonia.FUNDING: None.
- Published
- 2016
30. Phase II study of dose-modified busulfan by real-time targeting in allogeneic hematopoietic stem cell transplantation for myeloid malignancy
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Ritsuro Suzuki, Yoshihiro Inamoto, Takahiko Yasuda, Yachiyo Kuwatsuka, Masashi Sawa, Yoshihisa Morishita, Akio Kohno, Mariko Fukumoto, Nagoya Blood, Makoto Murata, Tomoki Naoe, Yoshiko Atsuta, Kazuyuki Shimada, Shigeki Saito, Koichi Miyamura, Koji Nagafuji, Takahiro Karasuno, Seitaro Terakura, and Shuichi Taniguchi
- Subjects
Adult ,Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Transplantation Conditioning ,Adolescent ,Cyclophosphamide ,medicine.medical_treatment ,Hepatic Veno-Occlusive Disease ,Graft vs Host Disease ,Phases of clinical research ,Hematopoietic stem cell transplantation ,Young Adult ,Recurrence ,Internal medicine ,medicine ,Clinical endpoint ,Humans ,Transplantation, Homologous ,Cumulative incidence ,Busulfan ,business.industry ,Graft Survival ,Hematopoietic Stem Cell Transplantation ,Original Articles ,General Medicine ,Middle Aged ,Myeloablative Agonists ,Surgery ,Clinical trial ,Transplantation ,Treatment Outcome ,Leukemia, Myeloid ,Female ,business ,medicine.drug - Abstract
We aimed to evaluate the efficacy and safety of allogeneic hematopoietic stem cell transplantation with targeted oral busulfan (BU) and cyclophosphamide (CY) in a phase II study. Busulfan (1.0 mg/kg) was given initially in six doses. Based on the estimated concentration at steady state after the first dose of BU, subsequent (7th-16th) doses were adjusted to obtain a targeted overall concentration at steady state of 700-900 ng/mL. The primary endpoint was 1-year overall survival (OS). Fifty patients were registered and 46 (median age, 53 years; range, 18-62 years) received planned transplant, including 24 with AML, 16 with myelodysplastic syndrome, and six with CML. Fourteen patients were categorized as standard risk. Nineteen patients received transplant from human leukocyte antigen-identical siblings, 27 from unrelated donors. The BU dose required reduction in 32 patients and escalation in six patients. One-year OS was 65% (95% confidence interval, 50-77%). Cumulative incidence of hepatic sinusoidal obstruction syndrome was 11%. One-year transplant-related mortality was 18%. Both OS and transplant-related mortality were favorable in this study, including patients of older age and with high risk diseases. Individual dose adjustment based on BU pharmacokinetics was feasible and effective in the current phase II study. This trial is registered in the University Hospital Medical Information Network Clinical Trial Registry System (UMIN-CTR, ID:C000000156).
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- 2012
31. Efficacy of ofatumumab against rituximab-resistant B-CLL/SLL cells with low CD20 protein expression
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Akihiro Tomita, Hitoshi Kiyoi, Kazuyuki Shimada, and Shigeki Saito
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CD20 ,biology ,business.industry ,Treatment outcome ,Hematology ,Drug resistance ,Ofatumumab ,Protein expression ,chemistry.chemical_compound ,chemistry ,Antibodies monoclonal ,medicine ,Cancer research ,biology.protein ,Rituximab ,business ,medicine.drug - Published
- 2014
32. USE OF THE STOP-BANG QUESTIONNAIRE AS A SCREENING TOOL FOR OSA IN PATIENTS WITH OR AT RISK FOR PULMONARY HYPERTENSION
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Shigeki Saito, Lesley Ann Saketkoo, Matthew R. Lammi, Bennett P. deBoisblanc, Monique Brown, and Michael Lanasa
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,business.industry ,Emergency medicine ,Medicine ,Screening tool ,In patient ,Stop bang ,Cardiology and Cardiovascular Medicine ,Critical Care and Intensive Care Medicine ,business ,medicine.disease ,Pulmonary hypertension - Published
- 2018
33. Efficacy and safety of autologous peripheral blood stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia
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Yasuhiko Miyata, Isamu Sugiura, Tetsuya Nishida, Seitaro Terakura, Shigeki Saito, Masaaki Yuge, Koichi Miyamura, Hitoshi Kiyoi, Hiroyoshi Nishikawa, Hiroatsu Iida, Akio Kohno, Satoshi Nishiwaki, Yachiyo Kuwatsuka, Masahide Osaki, Shingo Kurahashi, Masashi Sawa, Tatsunori Goto, Masanobu Kasai, and Makoto Murata
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Oncology ,medicine.medical_specialty ,Vincristine ,Chemotherapy ,business.industry ,medicine.medical_treatment ,General Medicine ,Philadelphia chromosome ,medicine.disease ,Minimal residual disease ,Dasatinib ,Transplantation ,03 medical and health sciences ,Regimen ,0302 clinical medicine ,Maintenance therapy ,hemic and lymphatic diseases ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,business ,030215 immunology ,medicine.drug - Abstract
Introduction The prognosis of Philadelphia chromosome positive acute lymphoblastic leukemia (Ph + ALL) has been dramatically improved since the introduction of tyrosine kinase inhibitors (TKIs). Although allogeneic hematopoietic cell transplantation (allo-HCT) is a major treatment option, the role of autologous peripheral blood stem cell transplantation (auto-PBSCT) has been reconsidered, especially in patients who achieved early molecular remission. Methods and analysis This is a multicenter exploratory study for Ph + ALL patients aged between 55 and 70 years who achieved complete molecular remission within 3 cycles of chemotherapy. The target sample size is 5, and the registration period is 2 years. The primary endpoint is Day100- mortality after transplantation, and the secondary endpoints are survival, relapse rate, nonrelapse mortality, and adverse events.This study is divided into 3 phases: peripheral blood stem cell harvest, transplantation, and maintenance. Chemomobilization is performed using a combination of cyclophosphamide (CPM), doxorubicin, vincristine (VCR), and prednisolone (PSL). As a preparative regimen, the LEED regimen is used, which consists of melphalan, CPM, etoposide, and dexamethasone. Twelve cycles of maintenance therapy using a combination of VCR, PSL, and dasatinib are performed.In association with relapse, the minimal residual disease (MRD) of BCR-ABL chimeric gene and T-cell subsets are analyzed both before and after auto-PBSCT. Ethics and dissemination The protocol was approved by the institutional review board of Nagoya University Hospital and all the participating hospitals. Written informed consent was obtained from all patients before registration, in accordance with the Declaration of Helsinki. Results of the study will be disseminated via publications in peer-reviewed journals. Trial registration Trial registration number UMIN000026445.
- Published
- 2017
34. PROPOSAL AND THE APPLICATION RESULTS OF EARTHQUAKE DAMAGE RISK EVALUATION METHOD OF EXTERNAL WALL IN DETACHED HOUSES
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Shigeki Saito and Seiichi Fukao
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Engineering ,business.industry ,Forensic engineering ,Structural engineering ,Deformation (meteorology) ,business ,Risk evaluation - Abstract
The aim of this research is to propose the earthquake damage risk evaluation method of external wall in detached houses, based on the result of the past experimental studies. Moreover, the validity of the method is verified by applying the technique in build-up areas.Fragility curves for buildings and the layer deformation capability of external wall were used to evaluate the damage risk of external wall by earthquake. Moreover, the external wall damage risk in three build-up areas was evaluated based on this method. Consequently, the risk of external wall damage in old build-up area is high.
- Published
- 2009
35. Increasing severity of status asthmaticus in an urban medical intensive care unit
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Janet M. Shapiro, Shigeki Saito, Dany Elsayegh, and Edward Eden
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Adult ,Male ,medicine.medical_specialty ,Substance-Related Disorders ,Leadership and Management ,medicine.medical_treatment ,Status Asthmaticus ,Assessment and Diagnosis ,Severity of Illness Index ,Hospitals, Urban ,Permissive hypercapnia ,Intensive care ,Severity of illness ,medicine ,Humans ,Anti-Asthmatic Agents ,Intensive care medicine ,Care Planning ,Retrospective Studies ,Asthma ,Mechanical ventilation ,business.industry ,Health Policy ,Medical record ,Smoking ,Retrospective cohort study ,General Medicine ,Middle Aged ,medicine.disease ,Respiration, Artificial ,Hospital medicine ,Intensive Care Units ,Treatment Outcome ,Emergency medicine ,Neuromuscular Blockade ,Female ,Fundamentals and skills ,business - Abstract
BACKGROUND: Life-threatening status asthmaticus (SA) requiring intensive care is a major concern given the rising prevalence of asthma. We examined episodes of SA requiring admission to the medical intensive care unit (MICU) of an urban hospital center. METHODOLOGY: The charts of patients admitted to the MICU of an urban hospital center with a diagnosis of SA during the 5-year period 2002–2006 were reviewed retrospectively. These results were compared with those of a previously published experience at our institution from 1995 to 1999. RESULTS: The medical records of 84 MICU admissions for SA were reviewed. There were 61 women (5 pregnant). The mean age was 44 years. Use of cigarettes or illicit drugs was found in 51% and 30%, respectively. Mechanical ventilation (MV) was required in 76% of admissions. Noninvasive ventilation was used in 10 patients. Neuromuscular blockade (NMB) was needed in 9% of admissions. The highest average PaCO2 during the first 24 hours was 67 mm Hg. Median duration of MV was 4.4 days. Six patients died, 3 of whom sustained prehospital cardiac arrest. Compared with the patients in the preceding 5-year period, the more recent patients had greater use of illicit drug and cigarettes. Patients presented with more severe asthma, as reflected by a higher PaCO2 and an increased duration of MV. CONCLUSIONS: During the recent 5-year period, we found a trend toward increasing severity of SA, as indicated by the degree of respiratory acidosis, need for NMB, and longer duration of MV. Access to medical care and cigarette and illicit drug use remain potential targets of primary intervention. Journal of Hospital Medicine 2008;3:206–211. © 2008 Society of Hospital Medicine.
- Published
- 2008
36. ESTIMATION OF EXTERIOR WALL REFURBISHMENT CYCLE OF DETACHED HOUSES USING PROPOTIONAL HAZARD MODEL
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Shigeki Saito, Seiichi Fukao, and Kozo Kadowaki
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Estimation ,Engineering ,business.industry ,Proportional hazards model ,Forensic engineering ,Hazard model ,business ,Civil engineering - Abstract
The purpose of this research is to clarify the specification and evaluation of a factor which affects presumption of an exterior wall refurbishment cycle by using a proportional hazard model. Covariates affecting exterior wall refurbishment were “Lath-mortar” and an “Area”. A Congested area of wooden built-up area has a long refurbishment cycle, and lath-mortar tends to shorten a refurbishment cycle. Moreover, an exterior wall refurbishment cycle will tend to become short if the number of times of repair increases, and it became clear that there is no difference of the refurbishment cycle by a construction age.
- Published
- 2008
37. Electrostatic Micromanipulation of a Conductive/Dielectric Particle by a Single Probe
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Shigeki Saito, T. Ochiai, Min Han, M. Sonoda, and Kunio Takahashi
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Materials science ,business.industry ,Analytical chemistry ,Substrate (electronics) ,Dielectric ,Electrostatics ,Acceleration voltage ,chemistry.chemical_compound ,chemistry ,Optoelectronics ,Particle ,Polystyrene ,business ,Electrical conductor ,Voltage - Abstract
This study reports the possibility of electrostatic micromanipulation of a conductive/dielectric particle using a single probe. The manipulation system consists of three objects: a conductive probe as a manipulating tool, a conductive plate as a substrate, and a conductive/dielectric particle that dubs as a micro-particle. For a conductive particle, a micromanipulation technique by applying accelerating and decelerating voltage with high switching rate is developed. We theoretically determine the desired voltage as the function of time by boundary element method, and experimentally verify the voltage effectively works with a 30-micrometer-in-diameter solder particle. For a dielectric particle, we experimentally demonstrate the successful picking-up of a 60-micrometer-in-diameter dielectric particle (phenol, polystyrene) from the substrate by electrostatic force. Besides, especially for a polystyrene particle, we observe the phenomenon of a micro-particle going back and forth between the substrate and the probe-tip like a micro-dribble even when just the constant voltage is applied. We discuss the possible mechanism of this interesting phenomenon and the feasibility of electrostatic manipulation for a dielectric micro-particle.
- Published
- 2007
38. Magnetic Hair for Wall Mobility
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Kenjiro Tadakuma, Kunio Takahashi, Jose Berengueres, and Shigeki Saito
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Engineering ,biology ,business.industry ,Mechanical engineering ,Scale factor ,biology.organism_classification ,symbols.namesake ,Classical mechanics ,Climbing ,Magnet ,symbols ,Gecko ,Shape function ,van der Waals force ,business - Abstract
We introduce a climbing system, inspired by gecko foot that uses magnets in place of Van der Waals interaction. This is possible because both forces, except for a scale factor, have similar force-curves. Taking advantage of this fact, we manufactured a hand-size "magnetic" version of a gecko-foot. This allowed us to conduct naked-eye experiments. As a result we identify four shape function relations that might partially explain the design of gecko feet. Additionally, we report experimental data, introduce a quantitative concept to compare climbing systems and show a prototype of magnetic hair
- Published
- 2006
39. Conditioning Regimen of Melphalan, Fludarabine and Total Body Irradiation in Unmanipulated HLA Haploidentical Stem Cell Transplantation Based on Feto-maternal Tolerance
- Author
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Kazuyuki Shimada, Yoshihisa Morishita, Shigeki Saito, Kazutaka Ozeki, Yukio Kato, Akio Kohno, and Hiroto Narimatsu
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Adult ,Male ,Melphalan ,medicine.medical_treatment ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,HLA Antigens ,Internal Medicine ,medicine ,Humans ,Transplantation, Homologous ,Antineoplastic Agents, Alkylating ,Multiple myeloma ,business.industry ,Hematopoietic Stem Cell Transplantation ,General Medicine ,Middle Aged ,Total body irradiation ,medicine.disease ,HLA Mismatch ,Histocompatibility ,Fludarabine ,Transplantation ,surgical procedures, operative ,Immunology ,Female ,business ,Immunosuppressive Agents ,Vidarabine ,Whole-Body Irradiation ,medicine.drug - Abstract
Unmanipulated hematopoietic stem cell transplantation from haploidentical family donors is frequently associated with graft failure and severe graft-versus-host disease (GVHD). We employed a myeloablative conditioning regimen consisting of 125 mg/m2 of fludarabine, 140 mg/m2 of melphalan and TBI of 10 to 12 Gy for three patients. The donor in each case was a haploidentical two-loci HLA mismatch mother or son. Engraftment failure was observed in one patient. In the other two patients, engraftment was confirmed within 15 days after transplantation. Acute and chronic GVHD was observed, but was controllable in both cases. HLA mismatched transplantation based on feto-maternal tolerance may provide an alternative option for patients who do not have HLA-matched donors.
- Published
- 2004
40. A scheme for micro-manipulation based on capillary force
- Author
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Shigeki Saito, Tomoyuki Motokado, Kunio Takahashi, and Kenichi J. Obata
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Materials science ,Force density ,business.industry ,Capillary action ,Mechanical Engineering ,Mechanics ,Condensed Matter Physics ,Capillary number ,Condensed Matter::Soft Condensed Matter ,Physics::Fluid Dynamics ,Optics ,Volume (thermodynamics) ,Mechanics of Materials ,business - Abstract
As the size of object diminishes, the effect of adhesional forces grows stronger for micro-manipulation and so. The capillary force generated by a liquid bridge can be greater than both the capillary force generated by another bridge and the adhesional force because the capillary force can be controlled by regulation of the liquid volume. We propose a micro-manipulation method based on the regulation of liquid bridge volume. A numerical investigation to estimate the capillary force from a given liquid volume is also presented, and four phases of capillary force curves are obtained from it. If an object is supported by two liquid bridges, we can predict which bridge collapse by a stability analysis for the wide range of liquid volume using the force curve.
- Published
- 2004
41. Image-based autonomous micromanipulation system for arrangement of spheres in a scanning electron microscope
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Shigeki Saito, Koichi Koyano, Tomio Yamaura, Hideki T. Miyazaki, Tomomasa Sato, and Takeshi Kasaya
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Materials science ,business.industry ,Scanning electron microscope ,Image processing ,Edge (geometry) ,law.invention ,Hough transform ,Optics ,Planar ,Optical microscope ,law ,SPHERES ,business ,Instrumentation ,Photonic crystal - Abstract
The micromanipulation technique in a scanning electron microscope (SEM) has been attracting interest as a technique to produce microstructures such as three-dimensional photonic crystals or advanced high-density electronic circuits. However, it is difficult to fabricate a large-scale structure or to conduct a systematic experiment using numbers of structures, as long as we rely on manually operated micromanipulation. In this study, we constructed an automatic system which arranges 10-μm-sized microspheres into a given two-dimensional pattern in a SEM. The spheres are picked up by touching with the center of the planar tip of a probe (needle), and placed on the substrate by moving the contact point to the edge of the tip and inclining the probe. The positions of the probe and the spheres are visually recognized from the SEM image from above and the optical microscope image from the side. The generalized Hough transform, which can robustly detect arbitrary shape from the edge fragments, is employed for the ...
- Published
- 2004
42. Electrostatic detachment of an adhering particle from a micromanipulated probe
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Shigeki Saito, Hideo Himeno, and Kunio Takahashi
- Subjects
Microscope ,Chemistry ,business.industry ,Electrostatic force microscope ,General Physics and Astronomy ,Mechanics ,Electrostatics ,law.invention ,Optics ,law ,Electric field ,Particle ,Boundary value problem ,business ,Boundary element method ,Voltage - Abstract
During micromanipulation, the influence of gravitational force becomes extremely small. The adhesional force is more significant for smaller objects. An adhered object can be detached by electrostatic interaction. In our earlier study, the electrostatic force generated by an applied voltage and the voltage required for detachment have been theoretically analyzed using the boundary element method (BEM). The system consists of a manipulation probe, a spherical microparticle, and a substrate plate. These objects are all conductive. In this study, the voltage for detachment of a microparticle with a 30-μm diameter is experimentally clarified, and is revealed to be in good agreement with the voltage predicted by BEM analysis. In addition, phenomena other than detachment are discussed based on observations through an optical video microscope. These results provide us with knowledge about the strategy for reliable electrostatic micromanipulation.
- Published
- 2003
43. Kinematics of mechanical and adhesional micromanipulation under a scanning electron microscope
- Author
-
Shigeki Saito, Tomomasa Sato, Kunio Takahashi, and Hideki T. Miyazaki
- Subjects
Materials science ,business.industry ,Scanning electron microscope ,Interface (computing) ,Rolling resistance ,General Physics and Astronomy ,Mechanical engineering ,Robotics ,Kinematics ,Lower limit ,Optics ,Fracture (geology) ,SMT placement equipment ,Artificial intelligence ,business - Abstract
In this paper, the kinematics of mechanical and adhesional micromanipulation using a needle-shaped tool under a scanning electron microscope is analyzed. A mode diagram is derived to indicate the possible micro-object behavior for the specified operational conditions. Based on the diagram, a reasonable method for pick and place operation is proposed. The keys to successful analysis are to introduce adhesional and rolling-resistance factors into the kinematic system consisting of a sphere, a needle-shaped tool, and a substrate, and to consider the time dependence of these factors due to the electron-beam (EB) irradiation. Adhesional force and the lower limit of maximum rolling resistance are evaluated quantitatively in theoretical and experimental ways. This analysis shows that it is possible to control the fracture of either the tool-sphere or substrate-sphere interface of the system selectively by the tool-loading angle and that such a selective fracture of the interfaces enables reliable pick or place operation even under EB irradiation. Although the conventional micromanipulation was not repeatable because the technique was based on an empirically effective method, this analysis should provide us with a guideline to reliable micromanipulation.
- Published
- 2002
44. Micro-object Pick and Place Operation under SEM based on Micro-physics
- Author
-
Tomomasa Sato, Hideki T. Miyazaki, and Shigeki Saito
- Subjects
Physics ,General Computer Science ,business.industry ,SMT placement equipment ,Computer vision ,Adhesion ,Artificial intelligence ,Electrical and Electronic Engineering ,business ,Object (computer science) - Abstract
Recently, techniques of arranging micrometer-sized objects under a scanning electron microscope (SEM) are required to construct micro-devices such as quantum optics devices. Since micro-objects tend to adhere to other objects mainly by electrostatic force, it is possible to pick them easily with a needle-tip instead of grasping by a gripper. However, it is difficult to place them on a substrate precisely, and furthermore even picking them is not achieved with enough reliability. To solve this problem, in this study, basic strategy for pick and place operation is indicated based on the actual measurement of adhesion under SEM first. Secondly dynamics for pick and place operation of a microsphere by a needle-shaped tool is analyzed. Thirdly a new method of practical pick and place is proposed on the basis of the basic strategy and the dynamics. Experimental system for executing the proposed operation is constructed based on the numeric-control of the position measurement of the target object. On this system, a lot of numeric-controlled experiments with 2µm polystyrene spheres reveal that under the optimal conditions, pick operation has never failed once out of over 20 trials and place operation has 140nm precision in position. From these results, this paper concludes that the proposed method can realize practical pick operation and place operation under SEM based on micro-physics.
- Published
- 2002
45. Educational Effectiveness and Implementation Challenge in Engineering Design Project by Radical Collaboration among People Having Different Expertise and/or Backgrounds
- Author
-
Shigeki Saito
- Subjects
Engineering ,Engineering management ,business.industry ,Systems engineering ,business ,Engineering design process - Published
- 2017
46. Dexamethasone palmitate ameliorates macrophages-rich graft-versus-host disease by inhibiting macrophage functions
- Author
-
Nobuhiko Imahashi, Tomoki Naoe, Yukiyasu Ozawa, Tetsuya Nishida, Kyosuke Takeshita, Seitaro Terakura, Tomonori Kato, Hiroki Mizuno, Aika Seto, Masafumi Ito, Shigeki Saito, Koichi Miyamura, Satoshi Nishiwaki, Takayuki Nakayama, Keisuke Nagao, Hidefumi Kato, Shinya Toyokuni, Ryuzo Ueda, and Makoto Murata
- Subjects
Male ,Graft vs Host Disease ,lcsh:Medicine ,Monocytes ,Dexamethasone ,White Blood Cells ,Mice ,Spectrum Analysis Techniques ,Animal Cells ,immune system diseases ,Molecular Cell Biology ,Medicine and Health Sciences ,Blood and Lymphatic System Procedures ,Macrophage ,Lymphocytes ,lcsh:Science ,Mice, Inbred BALB C ,Multidisciplinary ,Hematology ,Animal Models ,Flow Cytometry ,Immunohistochemistry ,medicine.anatomical_structure ,surgical procedures, operative ,Spectrophotometry ,Cytokines ,Female ,Cytophotometry ,Cellular Types ,medicine.symptom ,Research Article ,medicine.drug ,Cell type ,Drug Research and Development ,Immune Cells ,Immunology ,Surgical and Invasive Medical Procedures ,Mouse Models ,Inflammation ,Immunopathology ,Research and Analysis Methods ,Cell Line ,Model Organisms ,Dermis ,medicine ,Animals ,Humans ,Pharmacology ,Blood Cells ,business.industry ,Macrophages ,lcsh:R ,Biology and Life Sciences ,Cell Biology ,Molecular Development ,medicine.disease ,In vitro ,Mice, Inbred C57BL ,Disease Models, Animal ,Graft-versus-host disease ,Cell culture ,Immune System ,Clinical Immunology ,lcsh:Q ,business ,Cytometry ,Developmental Biology ,Stem Cell Transplantation - Abstract
Macrophage infiltration of skin GVHD lesions correlates directly with disease severity, but the mechanisms underlying this relationship remain unclear and GVHD with many macrophages is a therapeutic challenge. Here, we characterize the macrophages involved in GVHD and report that dexamethasone palmitate (DP), a liposteroid, can ameliorate such GVHD by inhibiting macrophage functions. We found that host-derived macrophages could exacerbate GVHD in a mouse model through expression of higher levels of pro-inflammatory TNF-α and IFN-γ, and lower levels of anti-inflammatory IL-10 than resident macrophages in mice without GVHD. DP significantly decreased the viability and migration capacity of primary mouse macrophages compared to conventional dexamethasone in vitro. DP treatment on day 7 and day 14 decreased macrophage number, and attenuated GVHD score and subsequent mortality in a murine model. This is the first study to provide evidence that therapy for GVHD should be changed on the basis of infiltrating cell type.
- Published
- 2014
47. Dynamics of Micro-object Operation Considering the Adhesive Effect under an SEM
- Author
-
Shigeki Saito, Tomomasa Sato, Tadao Onzawa, Hideki T. Miyazaki, and Kunio Takahashi
- Subjects
Engineering ,Optics ,Precision engineering ,business.industry ,Scanning electron microscope ,Rolling resistance ,Process (computing) ,Fracture (geology) ,SMT placement equipment ,Mechanical engineering ,Adhesive ,Substrate (printing) ,business - Abstract
This paper proposes a practical micro-object operation based on the dynamic analysis considering the adhesive effect under a scanning electron microscope (SEM). Recently, techniques of arranging micrometer-sized objects with high repeatability under a scanning electron microscope (SEM) are required to construct highly functional micro-devices. Since adhesion is dominant compared to gravity in the micro world, manipulation techniques using a needle-shaped tool by adhesive force are often adopted in basic researches where micro-objects are studied. These techniques, however, have not yet achieved the desired repeatability because many of these have been used just for the empirical reasons. Some even need the process of trial-and-error. Therefore, we analyze micro-object operation theoretically by introducing new physical factors, such as adhesive force and rolling-resistance, into the dynamic system consisting of a sphere, a needle-shaped tool, and a substrate. Through this analysis, we reveal that it is possible to fracture the contact interfaces selectively by controlling tool-loading angle reasonably. Based on the acquired knowledge, we also proposed the practical method of the pick and place operation of a micro-sphere under an SEM.
- Published
- 2001
48. Hydrothermal-method-grown ZnO single crystal as fast EUV scintillator for future lithography
- Author
-
Toyoaki Kimura, Tsuguo Fukuda, Keisuke Nagashima, T. Tatsumi, Dirk Ehrentraut, Masaharu Nishikino, Yuji Kagamitani, Toshihiko Shimizu, Shigeki Saito, Yusuke Furukawa, Hiroaki Nishimura, Momoko Tanaka, Kunioki Mima, Hidetoshi Murakami, Nobuhiko Sarukura, Tomoharu Nakazato, and Hiroshi Yamatani
- Subjects
Scintillation ,Chemistry ,business.industry ,Extreme ultraviolet lithography ,Scintillator ,Nanosecond ,Condensed Matter Physics ,Laser ,law.invention ,Inorganic Chemistry ,Crystal ,Optics ,law ,Extreme ultraviolet ,Materials Chemistry ,business ,Single crystal - Abstract
The temperature dependence of scintillation properties of a hydrothermal-method-grown zinc oxide (ZnO) emission is investigated using a nickel-like silver laser emitting at 13.9 nm. A broad peak at 386 nm with a full-width at half-maximum (FWHM) of 15 nm at room temperature (298 K) is obtained. The peak position tends to be blue shifted while the FWHM becomes narrower when the crystal temperature is decreased to 25 K. Streak images fitted by a double exponential decay reveal that the measured emission decay at 105 K was τ1=0.88 ns and τ2=2.7 ns. This decay time of a few nanoseconds is suitable for lithographic applications and is sufficiently short for the characterization of laser plasma extreme ultraviolet (EUV) sources with nanosecond durations.
- Published
- 2009
49. Cardiac Arrest Following Massive Pulmonary Embolism During Mechanical Declotting of Thrombosed Hemodialysis Fistula: Successful Resuscitation With tPA
- Author
-
Carmen Patrascu, Kaiser Toosy, Raymonde Jean, and Shigeki Saito
- Subjects
medicine.medical_specialty ,Percutaneous ,medicine.medical_treatment ,Fistula ,Critical Care and Intensive Care Medicine ,Tissue plasminogen activator ,Arteriovenous Shunt, Surgical ,Fibrinolytic Agents ,Renal Dialysis ,medicine ,Humans ,Aged, 80 and over ,business.industry ,Graft Occlusion, Vascular ,Heparin ,medicine.disease ,Cardiopulmonary Resuscitation ,Heart Arrest ,Surgery ,Pulmonary embolism ,Tissue Plasminogen Activator ,Female ,Dobutamine ,Hemodialysis ,Pulmonary Embolism ,business ,Complication ,medicine.drug - Abstract
Percutaneous declotting of a thrombosed fistula or graft is standard of care and is a safe procedure. Subclinical pulmonary embolism (PE) during this procedure occurs commonly, but symptomatic PE is extremely rare. The authors report a case of declotting-associated massive PE with cardiopulmonary arrest and successful resuscitation. The patient developed a new right-axis deviation and right-bundle branch block. Diagnosis of PE was confirmed with a computed tomography (CT) angiogram, and the patient received tissue plasminogen activator (tPA) and heparin. She required norepinephrine and dobutamine temporarily and was subsequently extubated successfully. Massive PE is a very rare complication of this procedure. Given the grave outcome, the clinical signs and symptoms should be recognized immediately and treatment instituted early.
- Published
- 2008
50. Mast cells promote the growth of Hodgkin's lymphoma cell tumor by modifying the tumor microenvironment that can be perturbed by bortezomib
- Author
-
Takayuki Nakayama, Kyosuke Takeshita, Tomoki Naoe, Norihiko Nakao, Hiroki Mizuno, Satoshi Nishiwaki, Yasuhiko Miyata, and Shigeki Saito
- Subjects
Cancer Research ,Angiogenesis ,Inflammation ,Antineoplastic Agents ,Mice, SCID ,Bortezomib ,Mice ,immune system diseases ,hemic and lymphatic diseases ,Cell Line, Tumor ,Tumor Microenvironment ,Medicine ,Animals ,Humans ,Mast Cells ,Cell Proliferation ,Tumor microenvironment ,business.industry ,Degranulation ,Hematology ,Hodgkin's lymphoma ,medicine.disease ,Boronic Acids ,Hodgkin Disease ,Lymphoma ,Mice, Inbred C57BL ,Oncology ,Pyrazines ,Immunology ,Female ,Stem cell ,medicine.symptom ,business ,medicine.drug - Abstract
Hodgkin's lymphoma is frequently associated with mast cell infiltration that correlates directly with disease severity, but the mechanisms underlying this relationship remain unclear. Here, we report that mast cells promote the growth of Hodgkin's tumor by modifying the tumor microenvironment. A transplantation assay shows that primary murine mast cells accelerate tumor growth by established Hodgkin's cell lines, and promote marked neovascularization and fibrosis. Both mast cells and Hodgkin's cells were sensitive to bortezomib, but mast cells were more resistant to bortezomib. However, bortezomib inhibited degranulation, PGE(2)-induced rapid release of CCL2, and continuous release of vascular endothelial growth factor-A from mast cells even at the concentration that did not induce cell death. Bortezomib-treated mast cells lost the ability to induce neovasculization and fibrosis, and did not promote the growth of Hodgkin tumor in vivo. These results provide further evidence supporting causal relationships between inflammation and tumor growth, and demonstrate that bortezomib can target the tumor microenvironment.
- Published
- 2012
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