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1. Relative telomere length impact on mortality of COVID‐19: Sex differences

Author

Ana Virseda‐Berdices, Leyre Concostrina‐Martinez, Oscar Martínez‐González, Rafael Blancas, Salvador Resino, Pablo Ryan, María Martin‐Vicente, Oscar Brochado‐Kith, Natalia Blanca‐López, María J. Mallol Poyato, Blanca López Matamala, Carmen Martín Parra, María Á Jiménez‐Sousa, Amanda Fernández‐Rodríguez, Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas), Instituto de Salud Carlos III, and Fundación Universidad Alfonso X el Sabio

Subjects
Male, Sex Characteristics, COVID-19, Telomere, Prognosis, Infectious Diseases, Virology, SARS-CoV2, Relative telomere length, Humans, Female, Mortality, Telomere Shortening, Aged
Abstract

Increasing age is associated with severity and higher mortality of COVID-19. Telomere shortening is associated with higher risk of infections and may be used to identify those patients who are more likely to die. We evaluated the association between relative telomere length (RTL) and COVID-19 mortality. RTL was measured in patients hospitalized because of COVID-19. We used Kaplan-Meier method to analyze survival probabilities, and Cox regression to investigate the association between RTL and mortality (30 and 90 days). Six hundred and eight patients were included in the analysis (mean age =72.5 years, 41.1% women, and 53.8% Caucasic). During the study period, 75 people died from COVID-19 and 533 survived. Lower RTL was associated with a higher risk of death in women either at 30 (adjusted hazard ratio [HR] (aHR) = 3.33; 95% confidence interval [CI] = 1.05-10.00; p = 0.040) and at 90 days (aHR = 3.57; 95%CI = 1.23-11.11; p = 0.019). Lower RTL was associated with a higher risk of dying of COVID-19 in women. This finding suggests that RTL has an essential role in the prognosis of this subset of the population. This study was supported by grants from Instituto de Salud Carlos III (ISCIII; grant number COV20/1144 [MPY224/20] to AFR/MAJS) and Fundación Universidad Alfonso X el Sabio (FUAX) – Santander (1.013.005). MAJS is Miguel Servet researcher supported and funded by ISCIII (grant number: CP17CIII/00007). The study was also supported by the Centro de Investigación Biomédica en Red (CIBER) en Enfermedades Infecciosas (CB21/13/00044). We also acknowledge the Spanish Coalition to Unlock Research on Host Genetics on COVID‐19 (SCOURGE). Sí

Published
2022
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2. Metabolic Profiling at COVID-19 Onset Shows Disease Severity and Sex-Specific Dysregulation

Author

Francisco C. Ceballos, Ana Virseda-Berdices, Salvador Resino, Pablo Ryan, Oscar Martínez-González, Felipe Peréz-García, María Martin-Vicente, Oscar Brochado-Kith, Rafael Blancas, Sofía Bartolome-Sánchez, Erick Joan Vidal-Alcántara, Oihane Elena Albóniga-Díez, Juan Cuadros-González, Natalia Blanca-López, Isidoro Martínez, Ignacio Ramirez Martinez-Acitores, Coral Barbas, Amanda Fernández-Rodríguez, María Ángeles Jiménez-Sousa, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), Unión Europea, Alfonso X el Sabio University (España), and Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas)

Subjects
Male, Disease onset, SARS-CoV-2, Immunology, Tryptophan, COVID-19, Severity of Illness Index, Severity, Cross-Sectional Studies, Disease Progression, Metabolomics, Immunology and Allergy, Cytokines, Humans, Spanish hospitals, Female, Sex-specific, Kynurenine, Retrospective Studies
Abstract

Background: metabolic changes through SARS-CoV-2 infection has been reported but not fully comprehended. This metabolic dysregulation affects multiple organs during COVID-19 and its early detection can be used as a prognosis marker of severity. Therefore, we aimed to characterize metabolic and cytokine profile at COVID-19 onset and its relationship with disease severity to identify metabolic profiles predicting disease progression. Material and methods: we performed a retrospective cross-sectional study in 123 COVID-19 patients which were stratified as asymptomatic/mild, moderate and severe according to the highest COVID-19 severity status, and a group of healthy controls. We performed an untargeted plasma metabolic profiling (gas chromatography and capillary electrophoresis-mass spectrometry (GC and CE-MS)) and cytokine evaluation. Results: After data filtering and identification we observed 105 metabolites dysregulated (66 GC-MS and 40 CE-MS) which shown different expression patterns for each COVID-19 severity status. These metabolites belonged to different metabolic pathways including amino acid, energy, and nitrogen metabolism among others. Severity-specific metabolic dysregulation was observed, as an increased transformation of L-tryptophan into L-kynurenine. Thus, metabolic profiling at hospital admission differentiate between severe and moderate patients in the later phase of worse evolution. Several plasma pro-inflammatory biomarkers showed significant correlation with deregulated metabolites, specially with L-kynurenine and L-tryptophan. Finally, we describe a strong sex-related dysregulation of metabolites, cytokines and chemokines between severe and moderate patients. In conclusion, metabolic profiling of COVID-19 patients at disease onset is a powerful tool to unravel the SARS-CoV-2 molecular pathogenesis. Conclusions: This technique makes it possible to identify metabolic phenoconversion that predicts disease progression and explains the pronounced pathogenesis differences between sexes. This study was supported by grants from Instituto de Salud Carlos III (ISCIII; grant number COV20/1144 (MPY224/20) to AF-R/MJ-S). The study was also funded by CIBER - Consorcio Centro de Investigación Biomédica en Red - (CB 2021; CB21/13/00044), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea - NextGenerationEU. AF-R and MJ-S are Miguel Servet researchers supported and funded by ISCIII (grant numbers: CP14CIII/00010 to AFR and CP17CIII/00007 to MJ-S). Universidad Alfonso X el Sabio, grant number 1.013.005 Sí

Published
2022

3. Plasma miRNA profile at COVID-19 onset predicts severity status and mortality

Author

Asier Fernández-Pato, Ana Virseda-Berdices, Salvador Resino, Pablo Ryan, Oscar Martínez-González, Felipe Pérez-García, María Martin-Vicente, Daniel Valle-Millares, Oscar Brochado-Kith, Rafael Blancas, Amalia Martínez, Francisco C. Ceballos, Sofía Bartolome-Sánchez, Erick Joan Vidal-Alcántara, David Alonso, Natalia Blanca-López, Ignacio Ramirez Martinez-Acitores, Laura Martin-Pedraza, María Ángeles Jiménez-Sousa, Amanda Fernández-Rodríguez, Instituto de Salud Carlos III, and Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas)

Subjects
EXPRESSION, Epidemiology, SARS-CoV-2, Immunology, severity, COVID-19, Infectious and parasitic diseases, RC109-216, General Medicine, VIRUS-INFECTION, Microbiology, mortality, QR1-502, Severity, MIR-150, MicroRNAs, Infectious Diseases, Virology, Drug Discovery, SARS-CoV2, miRNAs, Humans, Parasitology, Mortality, Biomarkers
Abstract

Background: MicroRNAs (miRNAs) have a crucial role in regulating immune response against infectious diseases, showing changes early in disease onset and before the detection of the pathogen. Thus, we aimed to analyze the plasma miRNA profile at COVID-19 onset to identify miRNAs as early prognostic biomarkers of severity and survival. Methods and results: Plasma miRNome of 96 COVID-19 patients that developed asymptomatic/mild, moderate and severe disease was sequenced together with a group of healthy controls. Plasma immune-related biomarkers were also assessed. COVID-19 patients showed 200 significant differentially expressed (SDE) miRNAs concerning healthy controls, with upregulated putative targets of SARS-CoV-2, and inflammatory miRNAs. Among COVID-19 patients, 75 SDE miRNAs were observed in asymptomatic/mild compared to symptomatic patients, which were involved in platelet aggregation and cytokine pathways, among others. Moreover, 137 SDE miRNAs were identified between severe and moderate patients, where miRNAs targeting the SARS CoV-2 genome were the most strongly disrupted. Finally, we constructed a mortality predictive risk score (miRNA-MRS) with ten miRNAs. Patients with higher values had a higher risk of 90-days mortality (hazard ratio = 4.60; p-value < 0.001). Besides, the discriminant power of miRNA-MRS was significantly higher than the observed for age and gender (AUROC = 0.970 vs. 0.881; p = 0.042). Conclusions: SARS-CoV-2 infection deeply disturbs the plasma miRNome from an early stage of COVID-19, making miRNAs highly valuable as early predictors of severity and mortality. This work was supported by Instituto de Salud Carlos III: [Grant Number COV20/1144, CP14CIII/00010, CP17CIII/00007, CPII20CIII/0001]. The study was also supported by the Centro de Investigación Biomédica en Red (CIBER) en Enfermedades Infecciosas (CB21/13/00044) Sí

Published
2022

4. Evolution Over Time of Ventilatory Management and Outcome of Patients With Neurologic Disease

Author

Tejerina E. E., Pelosi P., Robba C., Penuelas O., Muriel A., Barrios D., Frutos-Vivar F., Raymondos K., Du B., Thille A. W., Rios F., Gonzalez M., Del-Sorbo L., Marin M. D. C., Valle Pinheiro B., Soares M. A., Nin N., Maggiore S. M., Bersten A., Amin P., Cakar N., Young Suh G., Abroug F., Jibaja M., Matamis D., Ali Zeggwagh A., Sutherasan Y., Anzueto A., Esteban A, Fernando Ríos, Damian Violi, Marisol Rodríguez-Goñi, Roger Lamoglie, Fernando Villarejo, Norberto Tiribelli, Santiago Ilutovich, Matías Brizuela, Mariana Monllau, Fernando Saldarini, Silvina Borello, Alberto Marino, Mauricio Vinzio, Karina Bonasegla, Julián Hernández, María Belén Yapur, María Eugenia González, Sebastián E Mare, Judith Sagardía, Marco Bezzi, Cecilia Pereyra, Julian Strati, Daniel Vargas, Claudia Diaz, Pablo Gómez, Marcelo Palavecino, Graciela Elizabeth, Aguilera García, M Eugenia, Luis Pablo Cardonnet, Lisandro Betttini, Hernán Nuñez, Lucas Vallejo, Fernando Fernández, Jorge Arroyo, Daniel Duarte, Gerardo Filippa, Cayetano Galetti, Hernan Nunia, Fernando Lambert, Elisa Estenssoro, Marina Busico, Javier Horacio Álvarez, Alejandro Raimondi, Gustavo Badariotti, Martín Lugaro, Fernando Lipovestky, Alan Javier Zazu, Hugo Capponcelli, Patricia Vogl, Cristina Orlandi, Alejandro Gómez, Gustavo Jannello, Alejandro Risso, Leticia Rapetti, Guillermo Chiappero, Juan Domingo Fernández, Rodrigo E Gómez-Paz, Marcos Juan Zec, Pascual Valdez, Jorgelina Guyon, Ariel Chena, Sergio Lasdica, Martin Deheza, Schimdt Alejandra, Francisco Criado, Norma Beatriz Márquez, Pablo Desmery, José Luis Scapellato, Gonzalo Javier Ríos, Cristian Casabella, Jasmin Board, Andrew Davies, Andrew Bersten, Elisha Matheson, Amy Waters, John Santamaria, Jennifer Holmes, Cartan Costello, Manoj K Saxena, John Myburgh, Ellen Kinkel, Forbes McGain, Claire Cattigan, Allison Bone, Ian Seppelt, Leonie Weisbrodt, Cheryl Cuzner, Christopher MacIsaac, Deborah Barge, Tania Caf, Cameron Knott, Graeme Duke, Imogen Mitchell, Helen Rodgers, Rachel Whyte, Elisha Fulton, Alistair Nichol, Hergen Buscher, Priya Nair, Claire Reynolds, Simon J G Hockley, Ian Moore, Katherine Davidson, David Milliss, Raju Pusapati, Helen Wong, Jason Fletcher, Julie Smith, Paul Goldrick, Dianne Stephens, Jane Thomas, Anders Aneman, Sutrisno Gunawan, Tom Cowlam, George Lukas, Rick McAllister, Minka Springham, Joanne Sutton, Jeff Presneill, Tony Sutherland, Dianne Hill, Howard Connor, Jenny Dennett, Tim Coles, Freddy Sandy, Sando Chavarria, Marcelo Choque, Ronald Pairumani, Juan Guerra, Marco Antônio Soares Reis, José Carlos Versiani, Eduardo Fonseca Sad, Maria Aparecida Braga, Dinalva Aparecida Gomes, Fernando Antônio Botoni, Maurício Meireles Góes, Frederico Costa Val Barros, Rogério de Castro Pereira, Hugo Urbano, Valéria de Carvalho Magela, Aline Camile Yehia, Bruno Bonaccorsi Fernandino, Marco Antônio Ribeiro Leão, Rovílson Lara, Rubens Altair Amaral de Pádua, Janine Dias Alves, Aloísio Marques do Nascimento, Bruno do Valle Pinheiro, Carlos Alberto Studart Gomes, Marcelo Alcântara Holanda, Frederico Rodrigues Anselmo, Niall Ferguson, Neill Adhikari, Robert Fowler, Cheromi Sittambalam, Mehar-Un-Nisa Raja, Nicole Marinoff, Lauralyn McIntryre, Shawna Reddie, Laura Jones, Irene Watpool, Jeffrey Singh, Madison Dennis, Andrea Matte, Marc Lipkus, Ryan Albert, Andrew Steel, Emily Stern, Michael Miletin, Antonio Raso, Robyn Klages, Jan Friedrich, Orla Smith, Laura Wilson, Deborah Cook, Mark Bailey, Sangeeta Mehta, Stephen Lapinsky, Hannah Mathers, Cheryl Ethier, Stephanie Lubchansky, Samer Haj-Bakri, Dietrich Henzler, Lisa Julien, Luis Soto-Román, Juan Carlos Maurelia, César Antonio Maquilon, Luis Soto-Germani, Bin Du, Yan Kang, Bo Wang, Fachun Zhou, Fang Xu, Haibo Qiu, Yi Yang, Qingyuan Zhan, Bing Sun, Zhenjie Hu, Bin Yu, Xi Zhu, Yu Bai, Gang Li, Yi Li, Geng Zhang, Jianbiao Meng, Xiaobo Huang, Hong Pu, Daxing Yu, Chuanyun Qian, Wei Zhang, Yongjie Yin, Debiao Song, Yunxuan Yue, Zhengxuan Lv, Chengmin Yu, Qunmei Yao, Xue Wang, Yuan Xu, Wei He, Mian Chen, Zhihua Hu, Dongpo Jiang, Jian Huang, Wei Yu, Juanxian Gu, Yangong Chao, Zhixiang Li, Zhicheng Zhang, Wanxia Li, Zhenyang He, Jianguo Li, Chang Liu, Tiehe Qin, Shouhong Wang, Feng Li, Jun Jin, Jianhong Fu, Hongyang Xu, Hongyuan Lin, Jianying Guo, Yalin Liu, Jinghua Wang, Maoqin Li, Jiaqiong Li, Lei Chen, Qing Song, Liang Pan, Xianyao Wan, Jiuzhi Zhang, Weihai Yao, Yuhong Guo, Pang Wing Yan, Kelly Choy, Kwan Ming Chit, Patricia Leung, Chau Chin Man, Marco González, Ricardo Buitrago, Marcela Granados, Guillermo Ortiz, Cesar Enciso, Mario Gómez, Bladimir Alejandro Gil, Juan Pablo Sedano, Luis Fernando Castro Castro, Carlo Alberto Acosta, Marco Gonzalez, Francisco Molina, Camilo Pizarro, Mario Villabon, Carmelo Dueñas, Carlos Andrés Díaz, Nelson Fonseca, Rubén Camargo, Juan David Uribe, Hans-Henrik Bülow, Simona Beniczky, Jens Brushoj, Mikkel Præst, Birgitte Viebaek, Sine Wichman, Anette Mortensen, Susanne Andi Iversen, Bo Broberg, Edgard Luna, Manuel Jibaja, Leonardo Pazmiño, Katty Trelles, Fabricio Picoita, Gustavo Paredes, Vanesa Ramírez, Guillermo Falconí, Cristian Cevallos, Boris Villamagua, Marco Escobar, Freddy Sánchez, Miguel Llano, Miguel Lazcano, Ramiro Puetate, José Miguel Guerrero, Mijail Játiva, Myriam Montalvo, Franklin Villegas, Luis González Zambrano, Ronnie Mantilla, Gina Quinde, Andrea Gimenez, Luis Gonzalez Mosquera, Henry Caballero, María Fernanda García, Marcelo Ochoa, Soraya Puertas, Jackeline Coello, Mario Acosta, Medhat Soliman, Arnaud W Thille, Achille Kouatchet, Alain Mercat, Laurent Brochard, François Collet, Guillaume Marcotte, Pascal Beuret, Jean-Christophe M Richard, Gaëtan Bedunaeu, Pierre-Gildas Guitard, Fabien Soulis, Frédéric Bellec, Philippe Berger, Dorothée Carpentier, Benoit Veber, Salem Ould Zein, Géraldine Dessertaine, C Canevet, Fabien Grelon, Konstantinos Raymondos, Rolf Dembinski, Rolf Rossaint, Steffen Weber-Carstens, Christian Putensen, Maximillian Ragaller, Michael Quintel, Winfried Schubert, Thomas Bein, Heinrich Paulus, Walter Brandt, Lutz Pfeiffer, Silke Frenzel, Thoralf Kerner, P Kruska, Leila Eckholt, Joachim Hartung, Harald Fritz, Monika Holler, Johannes Busch, Andreas Viehöfer, Jens Buettner, Jörn Schlechtweg, Achim Lunkeit, Roland Schneider, Maria Wussow, Nils Marquardt, Christian Frenkel, Falk Hildebrandt, Tumbass Volker, Thomas Lipp, Cezar Mihailescu, Thomas Moellhoff, Thomas Steinke, Oliver Franke, Marcus Ruecker, Markus Schappacher, Steffen Appel, Heinz Kerger, Andreas Schwartz, Jan Dittmann, Jörg Haberkorn, Wolfgang Baier, Walter Seyde, Dimitros Matamis, Eleni Antoniadou, Pertsas Evangelos, Maria Giannakou, Zoltan Szentkereszty, Zsolt Molnar, Pravin Amin, Farhad N Kapadia, Nagarajan Ramakrishnan, Deepak Govil, Anitha Shenoy, Umesh G, Samir Sahu, Sheila Nainan Myatra, Subhash Kumar Todi, Sanjay Dhanuka, Mayur Patel, P Samaddar, Dhruva Chaudhry, Vivek Joshi, Srinivas Samavedam, Ankur Devendra Bhavsar, Prachee Sathe, Sujoy Mukherjee, Salvatore Maurizio Maggiore, Francesco Idone, Federica Antonicelli, Paolo Navalesi, Rosanna Vaschetto, Arianna Boggero, Rosalba Tufano, Michele Iannuzzi, Edoardo De Robertis, Romano Tetamo, Andrea Neville Cracchiolo, Antonio Braschi, Francesco Mojoli, Ilaria Curro', Mirko Belliato, Chiara Verga, Marta Ferrari, Erika Mannelli, Valerio Mangani, Giorgio Tulli, Francesca Frigieri, Armando Pedulla', Monica Rocco, Giorgia Citterio, Di Russo, Gaetano Perchiazzi, Loredana Pitagora, Antonio Pesenti, Michela Bombino, Davide Chiumello, Federica Tallarini, Serena Azzari, Antonina Pigna, Ivano Aprile, Marco Adversi, Antonio Corcione, Marianna Esposito, Annunziata Mattei, Vito Marco Ranieri, Rosario Urbino, Ilaria Maria Mastromauro, Antonino Giarratano, Maurizio Raineri Santi, Ambrogio Sansone, Younsuck Koh, Moo Suk Park, Je Hyeong Kim, Kyung Chan Kim, Hye Sook Choi, Yun Seong Kim, Jin Hwa Lee, Myung-Goo Lee, Won-Yeon Lee, Jin Young An, Gee Young Suh, Ki-Suck Jung, Asisclo J Villagómez Ortiz, César Cruz Lozano, Zalatiel Maycotte Luna, José Francisco López Baca, José Elizalde, Guillermo Cueto Robledo, Mario Alonso Treviño Salinas, Ricardo Martinez Zubieta, Claudia Olvera-Guzman, Marco Montes De Oca, Silvio A Ñamendys-Silva, José Salvador Martínez Cano, Jose Angel Baltazar Torres, Gustavo Morales Muñoz, Antonio Villa Delgado, Javier Ladape Martinez, Amine Ali Zeggwagh, Tarek Dendane, Abderrahim Azzouzi, Ahmed Sbihi, Wajdi Maazouzi, Mourad Amor, Charki Haimeur, Michael A Kuiper, Matty Koopmans, Uli Strauch, Dennis Bergmans, Serge Heines, Sylvia den Boer, Bas M Kors, Peter van der Voort, Paul J Dennesen, Bert Beishuizen, Ingrid van den Hul, Erna Alberts, Harry P P M Gelissen, Eduard Bootsma, Auke Reidinga, Kim Heus, Diane Mackle, Paul Young, Rachael Parke, Eileen Gilder, Jodi Brown, Lynette Newby, Catherine Simmonds, Jan Mehrtens, Seton Henderson, Tony Williams, Judi Tai, Chantal Hogan, Mary La Pine, John Durning, Sheree Gare, Troy Browne, Shirley Nelson, Jennifer Goodson, Julio Osorio, Chabu Coronado, Rollin Roldán Mori, Rosa Luz López Martínez, Adam Mikstacki, Barbara Tamowicz, Rui Moreno, Eduardo Almeida, Joana Silvestre, Heloisa Castro, Irene Aragão, Susana Alves Ferreira, Nelson Barros, Filomena Faria, Carlos André Correia Casado, Fausto Fialho Moura, Paulo Marcal, Ricardo Matos, Edward Nicolayenko, Mikhail Kirov, Andrey Yaroshetskiy, Andrei Piontek, Valery Subbotin, Yaseen Arabi, Olivia Dulfo, Chafrina Marie Olay, Edgardo E Tabhan, Nicolas Nin, Alfonso Muñoz, César Aragón, Ana Villagrá, Ainhoa Rosselló, Joan Maria Raurich, María Garitacelaya, Miguel Ángel González-Gallego, Francisco Ortuño, Miguel Fernández-Vivas, David Freire, Francisco Guerrero, Francisco Manzano, Juan Carlos, Alfredo Padrón, Pedro Rosa, Rafael Morales, Liliana Caipe, Maurizio Bottiroli, José María Nicolás, Marta Ugalde, Javier Ruiz, Lucia Capilla, Guillermo Muñiz, Jesús Sánchez-Ruiz, Javier Cebrián, Begoña Balerdi, Elena Parreño, Alvaro van Bommel, César Pérez-Calvo, Irene Dot, Javier Blanco, Raquel Manzanedo, José J Blanco, Daniel Fontaneda, Raúl González, Javier Díaz Domínguez, Alfonso Moreno, Antonio Reyes, Ian Carrasco, Itziar Mintegui, Rosa Sebastián, Javier García-Alonso, Carolina Lorencio, Josep Maria Sirvent, Patricia Jimeno, Miguel León, Pedro Galdos, Nuria Alonso, Julia López-Díaz, María Victoria de la Torre, Jorge Vidal Hernández, Nicolás Zamboschi, Francisco Lucena, Gemma Rialp, Raquel Montoiro, Victoria Goñi, María Ángeles Pena, Antonio Maestre, Marc Fabra, Jacinto Baena, Eva Benveniste, Susana Temprano, Jesús Sánchez, Carmen Campos, Sara Cabañes, María Elena Pérez-Losada, José Claudio Leo, Enrique Piacentini, María Del Carmen de la Torre, Laura Álvarez-Montero, Fernando Sánchez, Antonio Viñuales, Bernabé Álvarez, Javier Castañeda, Ángela Alonso, María Isabel Ruiz, Pedro Jesús Domínguez, Marcos Delgado, Eugenio Palazón, Antonio García-Jiménez, Rosa Álvaro, Clara Laplaza Eva Regidor, Enrique Maraví, José María Quiroga, Amalia Martínez de la Gandara, Cecilia Carbayo, María Luisa Navarrete, Manuel Valledor, Raquel Yano, José María Gutiérrez, Javier González-Robledo, Amparo Ferrandiz, Alberto Belenguer, Lidón Mateu, Laura Sayagues, María José Tolón, Nieves Franco, Elena Gallego, Félix Lacoma, Patricia Albert, Vicente Arraez, Mar Gobernado, Susana Moradillo, Carolina Gímenez-Esparza, Teresa Sánchez de Dios, Carlos Marian Crespo, Cecilia Hermosa, Federico Gordo, Genis Carrasco, María Ángeles Alonso, Alejandro Algora, Raúl de Pablo, Sofía García, Ana Carolina Caballero, José María Montón, Teresa Mut, Eva Manteiga, Alejandro de la Serna, Ana Esther Trujillo, Rafael Blancas, Inmaculada Vallverdú, José Manuel Serrano, Miquel Ferrer, Juan Diego Jiménez, Carlos Gallego, Dolores Vila, Luis Marina, Valentín Parra, Juan Ramón Cortés, Chen Chin-Ming, Ai-Chin Cheng, Fekri Abroug, Besbes Mohamed, Imed Chouchene, Mounir Bouaziz, Stambouli Neji, Islem Ouanes, Ayed Samia, Nahit Cakar, Ismail Kati, Ali Aydım Altunkan, Remzi Iscimen, Zafer Dogan, Bilge Çetin, Tayfun Adanir, Sabriye Guvenc, Unase Büyükkoçak, Antonio Anzueto, Ashley Ellis, Gary Kinasewitz, Allan Walkey, Phil Alkana, Gregory A Schmidt, Susan Gillen, Kathleen Lilli, Jennifer Twombley, Denice Wells, Larry Welder, Alejandro Arroliga, Alfredo Vasquez-Sandoval, Vincent John Scott, Craig Cernosek, Christopher Spradley, Dimple Tejwani, Sindhaghatta Venkatram, Gilda Diaz-Fuentes, Amber Monson, Anthony Saleh, Madhav Gudi, George Liziamma, Mohamed A Saad, Crissie De Spirito, Bryan Beatty, Samir Vermani, Crissie Despirito, Zaza Cohen, Amee Patrawalla, Samir Abdelhadi, Rupesh Vakil, Steven Y Chang, Brian Sherman, Rosanna Del Giudice, John Oropell, Timothy D Girard, Cayce Strength, Joyce Okahashi, Leanne Boehm, Matthew Kirchner, Erwin J Oei, Sebastian Circo, Nelson Medina, Mohammed Al-Jagbeer, V J Cardenas Jr, Smyth Smith, Shelby Sutton, Marcela Canola-Mazo, Tim Houlihan, Yogeet Kaur, Travis Parry, Craig A Piquette, Kerry Canady, Rahul Nanchal, Dana K Soetaert, Maria Del Mar Torres-Perez, Carlos Robles-Arias, William Rodriguez-Cintron, Mark Tidswell, Jennifer Germain, Lori-Ann Kozikowski, Erin Braden, Geneva Tatem, Javier Hurtado, Alberto Deicas, Daniel Weiss, Marta Beron, Román Garrido, Cristina Santos, Mario Cancela, Raúl Lombardi, Pedro Alzugaray, Jorge Gerez, Silvia Mareque, Graciela Franca, Oscar Cluzet, Edgardo Nuñez, Julio Pontet, Sergio Cáceres, Elias Caragna, Alberto Soler, Frank Torres, Gastón Pittini, Gabriel D Empaire, Stevens Salva, Fernando Pérez, Clara Pacheco, Zoraida Parra, Ingrid Von der Osten, Luis Williams, José Salinas, Do Danh Quynh, Pham Thi Van Anh, Nguyen Huu Hoang, Nghuyen Ba Tuan, RS: NUTRIM - R2 - Liver and digestive health, MUMC+: MA Arts Assistenten IC (9), Intensive Care, MUMC+: MA Medische Staf IC (9), Tejerina E.E., Pelosi P., Robba C., Penuelas O., Muriel A., Barrios D., Frutos-Vivar F., Raymondos K., Du B., Thille A.W., Rios F., Gonzalez M., Del-Sorbo L., Marin M.D.C., Valle Pinheiro B., Soares M.A., Nin N., Maggiore S.M., Bersten A., Amin P., Cakar N., Young Suh G., Abroug F., Jibaja M., Matamis D., Ali Zeggwagh A., Sutherasan Y., Anzueto A., Esteban A, and Fernando Ríos, Damian Violi, Marisol Rodríguez-Goñi, Roger Lamoglie, Fernando Villarejo, Norberto Tiribelli, Santiago Ilutovich, Matías Brizuela, Mariana Monllau, Fernando Saldarini, Silvina Borello, Alberto Marino, Norberto Tiribelli, Mauricio Vinzio, Karina Bonasegla, Julián Hernández, María Belén Yapur, María Eugenia González, Sebastián E Mare, Judith Sagardía, Marco Bezzi, Cecilia Pereyra, Julian Strati, Daniel Vargas, Claudia Diaz, Pablo Gómez, Marcelo Palavecino, Graciela Elizabeth, Aguilera García, M Eugenia, Luis Pablo Cardonnet, Lisandro Betttini, Hernán Nuñez, Lucas Vallejo, Fernando Fernández, Jorge Arroyo, Daniel Duarte, Gerardo Filippa, Cayetano Galetti, Hernan Nunia, Fernando Lambert, Elisa Estenssoro, Marina Busico, Fernando Villarejo, Javier Horacio Álvarez, Alejandro Raimondi, Gustavo Badariotti, Martín Lugaro, Fernando Lipovestky, Alan Javier Zazu, Hugo Capponcelli, Patricia Vogl, Cristina Orlandi, Alejandro Gómez, Gustavo Jannello, Alejandro Risso, Leticia Rapetti, Guillermo Chiappero, Juan Domingo Fernández, Rodrigo E Gómez-Paz, Marcos Juan Zec, Pascual Valdez, Jorgelina Guyon, Ariel Chena, Sergio Lasdica, Martin Deheza, Schimdt Alejandra, Francisco Criado, Norma Beatriz Márquez, Pablo Desmery, José Luis Scapellato, Gonzalo Javier Ríos, Cristian Casabella, Jasmin Board, Andrew Davies, Andrew Bersten, Elisha Matheson, Amy Waters, John Santamaria, Jennifer Holmes, Cartan Costello, Manoj K Saxena, John Myburgh, Ellen Kinkel, Forbes McGain, Claire Cattigan, Allison Bone, Ian Seppelt, Leonie Weisbrodt, Cheryl Cuzner, Christopher MacIsaac, Deborah Barge, Tania Caf, Cameron Knott, Graeme Duke, Imogen Mitchell, Helen Rodgers, Rachel Whyte, Elisha Fulton, Jasmin Board, Andrew Davies, Alistair Nichol, Hergen Buscher, Priya Nair, Claire Reynolds, Simon J G Hockley, Ian Moore, Katherine Davidson, David Milliss, Raju Pusapati, Helen Wong, Jason Fletcher, Julie Smith, Paul Goldrick, Dianne Stephens, Jane Thomas, Anders Aneman, Sutrisno Gunawan, Tom Cowlam, George Lukas, Rick McAllister, Minka Springham, Joanne Sutton, Jeff Presneill, Tony Sutherland, Dianne Hill, Howard Connor, Jenny Dennett, Tim Coles, Freddy Sandy, Sando Chavarria, Marcelo Choque, Ronald Pairumani, Juan Guerra, Marco Antônio Soares Reis, José Carlos Versiani, Eduardo Fonseca Sad, Maria Aparecida Braga, Dinalva Aparecida Gomes, Fernando Antônio Botoni, Maurício Meireles Góes, Frederico Costa Val Barros, Rogério de Castro Pereira, Hugo Urbano, Valéria de Carvalho Magela, Aline Camile Yehia, Bruno Bonaccorsi Fernandino, Marco Antônio Ribeiro Leão, Rovílson Lara, Rovílson Lara, Rubens Altair Amaral de Pádua, Janine Dias Alves, Aloísio Marques do Nascimento, Bruno do Valle Pinheiro, Carlos Alberto Studart Gomes, Marcelo Alcântara Holanda, Frederico Rodrigues Anselmo, Niall Ferguson, Neill Adhikari, Robert Fowler, Cheromi Sittambalam, Mehar-Un-Nisa Raja, Nicole Marinoff, Lauralyn McIntryre, Shawna Reddie, Laura Jones, Irene Watpool, Jeffrey Singh, Madison Dennis, Andrea Matte, Marc Lipkus, Ryan Albert, Andrew Steel, Emily Stern, Michael Miletin, Antonio Raso, Robyn Klages, Jan Friedrich, Orla Smith, Laura Wilson, Deborah Cook, Mark Bailey, Sangeeta Mehta, Stephen Lapinsky, Hannah Mathers, Cheryl Ethier, Stephanie Lubchansky, Samer Haj-Bakri, Dietrich Henzler, Lisa Julien, Luis Soto-Román, Juan Carlos Maurelia, César Antonio Maquilon, Luis Soto-Germani, Bin Du, Yan Kang, Bo Wang, Fachun Zhou, Fang Xu, Haibo Qiu, Yi Yang, Qingyuan Zhan, Bing Sun, Zhenjie Hu, Bin Yu, Xi Zhu, Yu Bai, Gang Li, Yi Li, Geng Zhang, Jianbiao Meng, Xiaobo Huang, Hong Pu, Bin Du, Daxing Yu, Chuanyun Qian, Wei Zhang, Yongjie Yin, Debiao Song, Yunxuan Yue, Zhengxuan Lv, Chengmin Yu, Qunmei Yao, Xue Wang, Yuan Xu, Wei He, Mian Chen, Zhihua Hu, Dongpo Jiang, Jian Huang, Wei Yu, Juanxian Gu, Yangong Chao, Zhixiang Li, Zhicheng Zhang, Wanxia Li, Zhenyang He, Jianguo Li, Chang Liu, Tiehe Qin, Shouhong Wang, Feng Li, Jun Jin, Jianhong Fu, Hongyang Xu, Hongyuan Lin, Jianying Guo, Yalin Liu, Jinghua Wang, Maoqin Li, Jiaqiong Li, Lei Chen, Qing Song, Liang Pan, Xianyao Wan, Jiuzhi Zhang, Weihai Yao, Yuhong Guo, Pang Wing Yan, Kelly Choy, Kwan Ming Chit, Patricia Leung, Chau Chin Man, Marco González, Ricardo Buitrago, Marcela Granados, Guillermo Ortiz, Cesar Enciso, Mario Gómez, Bladimir Alejandro Gil, Juan Pablo Sedano, Luis Fernando Castro Castro, Carlo Alberto Acosta, Marco Gonzalez, Francisco Molina, Camilo Pizarro, Mario Villabon, Carmelo Dueñas, Carlos Andrés Díaz, Nelson Fonseca, Rubén Camargo, Juan David Uribe, Hans-Henrik Bülow, Simona Beniczky, Jens Brushoj, Mikkel Præst, Birgitte Viebaek, Sine Wichman, Anette Mortensen, Susanne Andi Iversen, Bo Broberg, Edgard Luna, Manuel Jibaja, Leonardo Pazmiño, Katty Trelles, Fabricio Picoita, Gustavo Paredes, Vanesa Ramírez, Guillermo Falconí, Cristian Cevallos, Boris Villamagua, Marco Escobar, Freddy Sánchez, Miguel Llano, Miguel Lazcano, Ramiro Puetate, José Miguel Guerrero, Mijail Játiva, Myriam Montalvo, Franklin Villegas, Luis González Zambrano, Ronnie Mantilla, Gina Quinde, Andrea Gimenez, Luis Gonzalez Mosquera, Henry Caballero, María Fernanda García, Marcelo Ochoa, Soraya Puertas, Jackeline Coello, Mario Acosta, Medhat Soliman, Arnaud W Thille, Achille Kouatchet, Alain Mercat, Laurent Brochard, François Collet, Guillaume Marcotte, Pascal Beuret, Jean-Christophe M Richard, Gaëtan Bedunaeu, Pierre-Gildas Guitard, Fabien Soulis, Frédéric Bellec, Philippe Berger, Dorothée Carpentier, Benoit Veber, Salem Ould Zein, Géraldine Dessertaine, C Canevet, Fabien Grelon, Konstantinos Raymondos, Rolf Dembinski, Rolf Rossaint, Steffen Weber-Carstens, Christian Putensen, Maximillian Ragaller, Michael Quintel, Winfried Schubert, Thomas Bein, Heinrich Paulus, Walter Brandt, Lutz Pfeiffer, Silke Frenzel, Thoralf Kerner, P Kruska, Leila Eckholt, Joachim Hartung, Harald Fritz, Monika Holler, Johannes Busch, Andreas Viehöfer, Jens Buettner, Jörn Schlechtweg, Achim Lunkeit, Roland Schneider, Maria Wussow, Nils Marquardt, Christian Frenkel, Falk Hildebrandt, Tumbass Volker, Thomas Lipp, Cezar Mihailescu, Thomas Moellhoff, Thomas Steinke, Oliver Franke, Marcus Ruecker, Markus Schappacher, Steffen Appel, Heinz Kerger, Andreas Schwartz, Jan Dittmann, Jörg Haberkorn, Wolfgang Baier, Walter Seyde, Dimitros Matamis, Eleni Antoniadou, Pertsas Evangelos, Maria Giannakou, Zoltan Szentkereszty, Zsolt Molnar, Pravin Amin, Farhad N Kapadia, Nagarajan Ramakrishnan, Deepak Govil, Anitha Shenoy, Umesh G, Samir Sahu, Sheila Nainan Myatra, Subhash Kumar Todi, Sanjay Dhanuka, Mayur Patel, P Samaddar, Dhruva Chaudhry, Vivek Joshi, Srinivas Samavedam, Ankur Devendra Bhavsar, Prachee Sathe, Sujoy Mukherjee, Salvatore Maurizio Maggiore, Francesco Idone, Federica Antonicelli, Paolo Navalesi, Rosanna Vaschetto, Arianna Boggero, Rosalba Tufano, Michele Iannuzzi, Edoardo De Robertis, Romano Tetamo, Andrea Neville Cracchiolo, Antonio Braschi, Francesco Mojoli, Ilaria Curro', Mirko Belliato, Chiara Verga, Marta Ferrari, Erika Mannelli, Valerio Mangani, Giorgio Tulli, Francesca Frigieri, Armando Pedulla', Monica Rocco, Giorgia Citterio, Di Russo, Gaetano Perchiazzi, Loredana Pitagora, Antonio Pesenti, Michela Bombino, Davide Chiumello, Federica Tallarini, Serena Azzari, Antonina Pigna, Ivano Aprile, Marco Adversi, Antonio Corcione, Marianna Esposito, Annunziata Mattei, Vito Marco Ranieri, Rosario Urbino, Ilaria Maria Mastromauro, Antonino Giarratano, Maurizio Raineri Santi, Ambrogio Sansone, Younsuck Koh, Moo Suk Park, Je Hyeong Kim, Kyung Chan Kim, Hye Sook Choi, Yun Seong Kim, Jin Hwa Lee, Myung-Goo Lee, Won-Yeon Lee, Jin Young An, Gee Young Suh, Ki-Suck Jung, Asisclo J Villagómez Ortiz, César Cruz Lozano, Zalatiel Maycotte Luna, José Francisco López Baca, José Elizalde, Guillermo Cueto Robledo, Mario Alonso Treviño Salinas, Ricardo Martinez Zubieta, Claudia Olvera-Guzman, Marco Montes De Oca, Silvio A Ñamendys-Silva, José Salvador Martínez Cano, Jose Angel Baltazar Torres, Gustavo Morales Muñoz, Antonio Villa Delgado, Javier Ladape Martinez, Amine Ali Zeggwagh, Tarek Dendane, Abderrahim Azzouzi, Ahmed Sbihi, Wajdi Maazouzi, Mourad Amor, Charki Haimeur, Michael A Kuiper, Matty Koopmans, Uli Strauch, Dennis Bergmans, Serge Heines, Sylvia den Boer, Bas M Kors, Peter van der Voort, Paul J Dennesen, Bert Beishuizen, Ingrid van den Hul, Erna Alberts, Harry P P M Gelissen, Eduard Bootsma, Auke Reidinga, Jasmin Board, Andrew Davies, Kim Heus, Diane Mackle, Paul Young, Rachael Parke, Eileen Gilder, Jodi Brown, Lynette Newby, Catherine Simmonds, Jan Mehrtens, Seton Henderson, Tony Williams, Judi Tai, Chantal Hogan, Mary La Pine, John Durning, Sheree Gare, Troy Browne, Shirley Nelson, Jennifer Goodson, Julio Osorio, Chabu Coronado, Rollin Roldán Mori, Rosa Luz López Martínez, Adam Mikstacki, Barbara Tamowicz, Rui Moreno, Eduardo Almeida, Joana Silvestre, Heloisa Castro, Irene Aragão, Susana Alves Ferreira, Nelson Barros, Filomena Faria, Carlos André Correia Casado, Fausto Fialho Moura, Paulo Marcal, Ricardo Matos, Edward Nicolayenko, Mikhail Kirov, Andrey Yaroshetskiy, Andrei Piontek, Valery Subbotin, Yaseen Arabi, Olivia Dulfo, Chafrina Marie Olay, Edgardo E Tabhan, Nicolas Nin, Alfonso Muñoz, César Aragón, Ana Villagrá, Ainhoa Rosselló, Joan Maria Raurich, María Garitacelaya, Miguel Ángel González-Gallego, Francisco Ortuño, Miguel Fernández-Vivas, David Freire, Francisco Guerrero, Francisco Manzano, Juan Carlos, Alfredo Padrón, Pedro Rosa, Rafael Morales, Liliana Caipe, Maurizio Bottiroli, José María Nicolás, Marta Ugalde, Javier Ruiz, Lucia Capilla, Guillermo Muñiz, Jesús Sánchez-Ruiz, Javier Cebrián, Begoña Balerdi, Elena Parreño, Alvaro van Bommel, César Pérez-Calvo, Irene Dot, Javier Blanco, Raquel Manzanedo, José J Blanco, Daniel Fontaneda, Raúl González, Javier Díaz Domínguez, Alfonso Moreno, Antonio Reyes, Ian Carrasco, Itziar Mintegui, Rosa Sebastián, Javier García-Alonso, Carolina Lorencio, Josep Maria Sirvent, Patricia Jimeno, Miguel León, Pedro Galdos, Nuria Alonso, Julia López-Díaz, María Victoria de la Torre, Jorge Vidal Hernández, Nicolás Zamboschi, Francisco Lucena, Gemma Rialp, Raquel Montoiro, Victoria Goñi, María Ángeles Pena, Antonio Maestre, Marc Fabra, Jacinto Baena, Eva Benveniste, Susana Temprano, Jesús Sánchez, Carmen Campos, Sara Cabañes, María Elena Pérez-Losada, José Claudio Leo, Enrique Piacentini, María Del Carmen de la Torre, Laura Álvarez-Montero, Fernando Sánchez, Antonio Viñuales, Bernabé Álvarez, Javier Castañeda, Ángela Alonso, María Isabel Ruiz, Pedro Jesús Domínguez, Marcos Delgado, Eugenio Palazón, Antonio García-Jiménez, Rosa Álvaro, Clara Laplaza Eva Regidor, Enrique Maraví, José María Quiroga, Amalia Martínez de la Gandara, Cecilia Carbayo, María Luisa Navarrete, Manuel Valledor, Raquel Yano, José María Gutiérrez, Javier González-Robledo, Amparo Ferrandiz, Alberto Belenguer, Lidón Mateu, Laura Sayagues, María José Tolón, Nieves Franco, Elena Gallego, Félix Lacoma, Patricia Albert, Vicente Arraez, Mar Gobernado, Susana Moradillo, Carolina Gímenez-Esparza, Teresa Sánchez de Dios, Carlos Marian Crespo, Cecilia Hermosa, Federico Gordo, Genis Carrasco, María Ángeles Alonso, Alejandro Algora, Raúl de Pablo, Sofía García, Ana Carolina Caballero, José María Montón, Teresa Mut, Eva Manteiga, Alejandro de la Serna, Ana Esther Trujillo, Rafael Blancas, Inmaculada Vallverdú, José Manuel Serrano, Miquel Ferrer, Juan Diego Jiménez, Carlos Gallego, Dolores Vila, Luis Marina, Valentín Parra, Juan Ramón Cortés, Chen Chin-Ming, Ai-Chin Cheng, Fekri Abroug, Besbes Mohamed, Imed Chouchene, Mounir Bouaziz, Stambouli Neji, Islem Ouanes, Ayed Samia, Nahit Cakar, Ismail Kati, Ali Aydım Altunkan, Remzi Iscimen, Zafer Dogan, Bilge Çetin, Tayfun Adanir, Sabriye Guvenc, Unase Büyükkoçak, Antonio Anzueto, Ashley Ellis, Gary Kinasewitz, Allan Walkey, Phil Alkana, Gregory A Schmidt, Susan Gillen, Kathleen Lilli, Jennifer Twombley, Denice Wells, Larry Welder, Alejandro Arroliga, Alfredo Vasquez-Sandoval, Vincent John Scott, Craig Cernosek, Christopher Spradley, Dimple Tejwani, Sindhaghatta Venkatram, Gilda Diaz-Fuentes, Amber Monson, Anthony Saleh, Madhav Gudi, George Liziamma, Mohamed A Saad, Crissie De Spirito, Bryan Beatty, Samir Vermani, Crissie Despirito, Zaza Cohen, Amee Patrawalla, Samir Abdelhadi, Rupesh Vakil, Steven Y Chang, Brian Sherman, Rosanna Del Giudice, John Oropell, Timothy D Girard, Cayce Strength, Joyce Okahashi, Leanne Boehm, Matthew Kirchner, Ashley Ellis, Gary Kinasewitz, Erwin J Oei, Sebastian Circo, Nelson Medina, Mohammed Al-Jagbeer, V J Cardenas Jr, Smyth Smith, Shelby Sutton, Marcela Canola-Mazo, Tim Houlihan, Yogeet Kaur, Travis Parry, Craig A Piquette, Kerry Canady, Rahul Nanchal, Dana K Soetaert, Maria Del Mar Torres-Perez, Carlos Robles-Arias, William Rodriguez-Cintron, Mark Tidswell, Jennifer Germain, Lori-Ann Kozikowski, Erin Braden, Geneva Tatem, Javier Hurtado, Alberto Deicas, Daniel Weiss, Marta Beron, Román Garrido, Cristina Santos, Mario Cancela, Raúl Lombardi, Pedro Alzugaray, Jorge Gerez, Silvia Mareque, Graciela Franca, Oscar Cluzet, Edgardo Nuñez, Julio Pontet, Sergio Cáceres, Elias Caragna, Alberto Soler, Frank Torres, Gastón Pittini, Gabriel D Empaire, Stevens Salva, Fernando Pérez, Clara Pacheco, Zoraida Parra, Ingrid Von der Osten, Luis Williams, José Salinas, Do Danh Quynh, Pham Thi Van Anh, Nguyen Huu Hoang, Nghuyen Ba Tuan

Subjects
Male, medicine.medical_treatment, pulmonary complications, RESPIRATORY-DISTRESS-SYNDROME, Critical Care and Intensive Care Medicine, CASE-FATALITY, 0302 clinical medicine, Risk Factors, Brain Injuries, Traumatic, Multicenter Studies as Topic, Hospital Mortality, Prospective Studies, Simplified Acute Physiology Score, Stroke, POPULATION, Age Factors, ANEURYSMAL SUBARACHNOID HEMORRHAGE, Middle Aged, Hemorrhagic Stroke, Intensive Care Units, Observational Studies as Topic, Anesthesia, Breathing, Female, medicine.symptom, Ventilator Weaning, Cohort study, Adult, TRAUMATIC BRAIN-INJURY, Pressure support ventilation, mechanical ventilation, prognosis factors, ACUTE LUNG INJURY, 03 medical and health sciences, medicine, Humans, Aged, Ischemic Stroke, Mechanical ventilation, Noninvasive Ventilation, business.industry, MORTALITY, neurologic patients, Organ dysfunction, 030208 emergency & critical care medicine, Length of Stay, medicine.disease, TRENDS, Respiration, Artificial, 030228 respiratory system, Etiology, NEUROCRITICAL CARE, Nervous System Diseases, Tracheotomy, business
Abstract

OBJECTIVES: To describe the changes in ventilator management over time in patients with neurologic disease at ICU admission and to estimate factors associated with 28-day hospital mortality. DESIGN: Secondary analysis of three prospective, observational, multicenter studies. SETTING: Cohort studies conducted in 2004, 2010, and 2016. PATIENTS: Adult patients who received mechanical ventilation for more than 12 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 20,929 patients enrolled, we included 4,152 (20%) mechanically ventilated patients due to different neurologic diseases. Hemorrhagic stroke and brain trauma were the most common pathologies associated with the need for mechanical ventilation. Although volume-cycled ventilation remained the preferred ventilation mode, there was a significant (p < 0.001) increment in the use of pressure support ventilation. The proportion of patients receiving a protective lung ventilation strategy was increased over time: 47% in 2004, 63% in 2010, and 65% in 2016 (p < 0.001), as well as the duration of protective ventilation strategies: 406 days per 1,000 mechanical ventilation days in 2004, 523 days per 1,000 mechanical ventilation days in 2010, and 585 days per 1,000 mechanical ventilation days in 2016 (p < 0.001). There were no differences in the length of stay in the ICU, mortality in the ICU, and mortality in hospital from 2004 to 2016. Independent risk factors for 28-day mortality were age greater than 75 years, Simplified Acute Physiology Score II greater than 50, the occurrence of organ dysfunction within first 48 hours after brain injury, and specific neurologic diseases such as hemorrhagic stroke, ischemic stroke, and brain trauma. CONCLUSIONS: More lung-protective ventilatory strategies have been implemented over years in neurologic patients with no effect on pulmonary complications or on survival. We found several prognostic factors on mortality such as advanced age, the severity of the disease, organ dysfunctions, and the etiology of neurologic disease.

Published
2021
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5. Results of a Prospective Study to Evaluate the Impact of Point‐of‐Care Ultrasound in the Enhancement of Gastrointestinal Bleeding Risk Scores

Author

Julio Cobo Mora, Yale Tung Chen, Tomás Villén Villegas, César Carballo Cardona, Rafael Blancas Gómez-Casero, and Manuel Quintana Díaz

Subjects
Male, medicine.medical_specialty, Gastrointestinal bleeding, Point-of-Care Systems, Risk Assessment, Severity of Illness Index, Inferior vena cava, Gastroenterology, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Hypovolemia, parasitic diseases, medicine, Humans, Radiology, Nuclear Medicine and imaging, Prospective Studies, Prospective cohort study, Aged, Ultrasonography, 030219 obstetrics & reproductive medicine, Radiological and Ultrasound Technology, business.industry, Area under the curve, Emergency department, Odds ratio, Prognosis, medicine.disease, medicine.vein, Female, medicine.symptom, Emergency Service, Hospital, Gastrointestinal Hemorrhage, Rockall score, business, human activities
Abstract

Objectives Gastrointestinal (GI) bleeding is a common illness seen in the emergency department. The prognosis varies from self-limited to potentially life threatening. Currently available GI bleeding risk scores have only a modest predictive value, limiting their wide implementation. The aim of this study was to assess the association and capability of point-of-care ultrasound (POCUS) used by emergency physicians to improve common GI bleeding scores for predicting complications and long-term outcomes of patients with GI bleeding, which to our knowledge have never been studied. Methods Between August 2015 and April 2017, 203 hemodynamically stable patients with acute GI bleeding admitted to the emergency department were prospectively investigated. Using ultrasound, we measured the inferior vena cava diameter, cardiac output with surrogate markers such as the velocity time integral before and after the passive leg-raising test, and the presence of systolic obliteration of the left ventricle. The Rockall and Glasgow-Blatchford scores were calculated for patients with upper GI bleeding and the Velayos score for lower GI bleeding. The patients had follow-up during hospitalization and 30 days later to assess for early and late adverse events (AEs). Then we integrated the ultrasound findings of hypovolemia into the GI bleeding scores, assessing the capability to detect AEs. Results In our cohort, patients with upper GI bleeding who showed left ventricle kissing walls had a worse evolution, with a greater presence of late AEs (odds ratio [OR], 3.8; 95% confidence interval [CI], 1.32-10.96; P = .01). Patients with lower GI bleeding who showed a collapse of the inferior vena cava (>50%) after passive leg raising had a greater presence of early AEs (OR, 3.6; 95% CI, 1.46-9.00; P = .004). The predictive performance of the Rockall score (receiver operating characteristic analysis: area under the curve [AUC], 77.6%; 95% CI, 66.3%-88.8%) increased with POCUS (AUC, 80.3%; 95% CI, 69.5%-91.1%); that of the Glasgow-Blatchford score (AUC, 72.5%; 95% CI, 59.9%-85.2%) increased with POCUS (AUC, 73.2%; 95% CI, 61.1%-85.4%); and that of Velayos score (AUC, 55.7%; 95% CI, 42.5%-69.0%) also increased with POCUS (AUC, 72.2%; 95% CI, 61.1%-83.3%). Conclusions The use of POCUS in GI bleeding is feasible and enhances common GI bleeding risk scores, showing better predictive performance in detecting AEs.

Published
2019
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6. Characteristics of patients with myocardial infarction with nonobstructive coronary arteries (MINOCA ) from the ARIAM-SEMICYUC registry: development of a score for predicting MINOCA

Author

Carmen Martín-Parra, Manuel Quintana-Díaz, Daniel Ballesteros-Ortega, Eva de Miguel-Balsa, Miriam Chana-García, Oscar Martinez-Gonzalez, Blanca López-Matamala, M Ángeles Alonso-Fernández, Rafael Blancas Gomez-Casero, and Madián Manso-Álvarez

Subjects
Male, Endocrinology, Diabetes and Metabolism, Myocardial Infarction, Coronary Artery Disease, 030204 cardiovascular system & hematology, Coronary Angiography, Coronary artery disease, 0302 clinical medicine, Risk Factors, score, Pharmacology (medical), Registries, 030212 general & internal medicine, Myocardial infarction, Original Research, MINOCA, education.field_of_study, medicine.diagnostic_test, Mortality rate, Age Factors, Hematology, General Medicine, Middle Aged, Prognosis, Troponin, Up-Regulation, medicine.anatomical_structure, Cardiology, Female, Cardiology and Cardiovascular Medicine, Cohort study, Acute coronary syndrome, medicine.medical_specialty, Population, acute myocardial infarction, nonobstructive coronary disease, Decision Support Techniques, Diagnosis, Differential, 03 medical and health sciences, Sex Factors, Predictive Value of Tests, Internal medicine, medicine, Humans, education, Aged, Retrospective Studies, business.industry, Coronary Stenosis, Public Health, Environmental and Occupational Health, medicine.disease, Vascular Health and Risk Management, Coronary arteries, Spain, Angiography, coronary syndrome, business, Biomarkers
Abstract

Daniel Ballesteros-Ortega,1 Oscar Martínez-González,1 Rafael Blancas Gómez-Casero,1 Manuel Quintana-Díaz,2 Eva de Miguel-Balsa,3 Carmen Martín-Parra,1 Blanca López-Matamala,1 Miriam Chana-García,1 M Ángeles Alonso-Fernández,1 Madián Manso-Álvarez1 On behalf of the ARIAM-SEMICYUC Group 1Critical Care Department, Hospital Universitario del Tajo, CP 28300, Aranjuez, Spain; 2Critical Care Department, Hospital Universitario La Paz, 28046 Madrid, Spain; 3Critical Care Department, Hospital General Universitario de Elche, 03203 Elche, Alicante, Spain Background: Acute myocardial infarction (AMI) with no evidence of relevant stenosis of the coronary artery, known as myocardial infarction (MI) with nonobstructive coronary arteries (MINOCA), has a prevalence of up to 14%. The various causes of MINOCA lead to damage of the myocardium, and there are marked differences in diagnoses, prognoses, and treatments. Although the number of patients affected is considerable owing to the high prevalence of acute coronary syndrome (ACS), the causes of MINOCA have received little attention with the result that some patients may not receive appropriate treatment. Awareness of this disease among clinicians has started only to improve since the beginning of the current century. The aim of this study was to develop a score that enables patients with MINOCA to be distinguished from patients with MI with coronary artery disease (MI-CAD) and thus to facilitate appropriate diagnosis and therapy. Patients and methods: A multicenter observational cohort study was designed. All patients aged ≥18 years from the ARIAM-SEMICYUC (Analysis of Delay in AMI-Spanish Society of Intensive Care Medicine and Coronary Unit) registry, diagnosed with AMI, and admitted to critical care units or coronary care units (CCUs) were included. Patients were classified into two groups: MINOCA, comprising patients with no significant lesions on angiography, and MI-CAD, comprising patients with lesions of the coronary artery tree. Results: A score based on standard variables to assess the probability of MINOCA on admission was designed, showing a maximum value corresponding to a 40% probability of MINOCA. The discriminative power of the model was 0.756 (P-value for the Hosmer–Lemeshow test was >0.05). At 30-day follow-up, the mortality rate was higher for MI-CAD patients. Conclusion: Patients with MINOCA constitute a population that differs from other patients with AMI. Their differential characteristics require a certain diagnostic effort to align therapy with the disease causing the ischemic event. This score could prove useful in establishing additional diagnostic procedures. Keywords: MINOCA, acute myocardial infarction, nonobstructive coronary disease, coronary syndrome, score

Published
2019
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7. Inspiratory collapse of the inferior vena cava and the kissing ventricle sign: markers of poor prognosis in emergency gastrointestinal bleeding

Author

Yale, Tung Chen, Rafael, Blancas Gómez-Casero, Manuel, Quintana Díaz, and Belén, Oliva

Subjects
Adult, Male, Heart Ventricles, Hypovolemia, Vena Cava, Inferior, Middle Aged, Prognosis, Risk Assessment, Humans, Female, Prospective Studies, Emergency Service, Hospital, Gastrointestinal Hemorrhage, Aged, Ultrasonography
Abstract

Gastrointestinal bleeding, one of the main reasons for emergency department visits, is associated with significant mortality, complications, and high health care spending. Studies have shown the usefulness of hemodynamic monitoring by ultrasound of the inferior vena cava (IVC), imaging of systolic obstruction of the left ventricle (the kissing sign), changes in cardiac output, or surrogates for cardiac output such as the left ventricular velocity time integral before and after a passive leg raise. There is currently no evidence for applying this approach to evaluating hypovolemia due to gastrointestinal bleeding.We prospectively recruited 203 emergency department patients with gastrointestinal bleeding between August 2015 and April 2017; this sample size provided a 95% CI for a proportion of 5%, with a precision of 3% and expected losses of 15%. Recorded data were as follows: medical histories, observations during physical examinations, laboratory results, diagnostic variables, treatment details, clinical course, and ultrasound findings related to hemodynamics.Clinical course was worse in patients with evidence of hypovolemia such as a small (1 cm) end-expiratory IVC diameter (IVCEE) or the kissing sign. Complications were more prevalent at 24 hours and 30 days, a finding that was not associated with the other clinical or laboratory variables commonly monitored. We also saw that both a small IVCEE and persistent inspiratory collapse of the IVC of more than 50% after a passive leg raise test might prove useful for identifying patients at risk for anemia at 24 hours, allowing time to start preventive measures.The analysis of IVCEE, inspiratory collapse of the IVC, or the kissing sign in combination with clinical and laboratory findings can facilitate the use of clinical practice algorithms that can encourage the efficient risk-based assignment of resources and improve prognosis.La hemorragia digestiva (HD) constituye un problema médico con significativa morbimortalidad y elevado consumo de recursos sanitarios, y es uno de los motivos principales de consulta en los servicios de urgencias. Varios estudios han destacado la utilidad de la ecografía clínica en la monitorización hemodinámica, a partir del análisis de la vena cava inferior (VCI), visualizando la obliteración sistólica del ventrículo izquierdo (“kissing del VI”) así como cambios en el gasto cardíaco (GC) o marcadores subrogados al GC como la integral velocidad tiempo (IVT) en el tracto de salida del VI, antes y después de la prueba de elevación pasiva de miembros inferiores (EPMI). En la actualidad, no hay evidencia directa relacionada con la aplicabilidad de este enfoque en la hipovolemia por HD.Entre agosto de 2015 y abril de 2017, se reclutaron prospectivamente 203 pacientes (nivel de confianza del 95%, precisión 3%, proporción 5%, pérdidas estimadas 15%), que consultaron en el servicio de urgencias por HD. Se recogieron los antecedentes médicos, la exploración física, los hallazgos analíticos, variables relacionadas con el diagnóstico, con el tratamiento, con la evolución clínica y variables ecográficas relacionadas con la situación hemodinámica.Los pacientes con datos de hipovolemia como un diámetro de VCI espiratorio (CAVAesp)1 cm o un “kissing del VI” presentaron peor evolución, con mayor presencia de complicaciones a las 24 horas y 30 días, hallazgo que no se observó con otros parámetros clínicos o analíticos comúnmente empleados. Además se observó que tanto la CAVAesp1 cm, como la persistencia del colapso inspiratorio de la VCI (CICAVA)50% tras la PLR podrían ser de utilidad para identificar a los pacientes en los que es esperable una anemización a las 24 horas.El análisis de marcadores ecográficos como la CAVAesp, CIVACA o el “kissing del VI”, combinados con variables clínicas y de laboratorio, permitiría implementar algoritmos de actuación más eficientes y asignar mejor los recursos en función del perfil de riesgo, lo cual podría conducir a una mejora en el pronóstico.

Published
2019

8. Early vs Conventional Extubation After Cardiac Surgery With Cardiopulmonary Bypass

Author

Begoña Morato, Gema Vega, Rafael Blancas, Antonio Reyes, Jose-Luis Moreno, Carmen Torrecilla, and Enrique Cereijo

Subjects
Male, Pulmonary and Respiratory Medicine, Artificial ventilation, medicine.medical_specialty, Time Factors, Sedation, medicine.medical_treatment, Critical Care and Intensive Care Medicine, law.invention, Postoperative Complications, Randomized controlled trial, Risk Factors, law, Intensive care, Intubation, Intratracheal, medicine, Humans, Intubation, Prospective Studies, Treatment Failure, Cardiac Surgical Procedures, APACHE, Postoperative Care, Mechanical ventilation, Cardiopulmonary Bypass, business.industry, Incidence, Extracorporeal circulation, Length of Stay, Middle Aged, Surgery, Cardiac surgery, Intensive Care Units, Anesthesia, Female, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Ventilator Weaning
Abstract

Objectives Sedation and ventilation overnight after cardiac surgery is common practice. However, early extubation may be feasible with no increase in postoperative complications. This study examines (1) if early extubation is possible in a significant number of patients, (2) if it reduces ICU stay, and (3) if this practice increases postoperative complications. Design Prospective, controlled, randomized clinical trial. Patients and methods We randomized 404 consecutive patients to early extubation (7 to 11 h postoperatively) (group A, 201 patients) or conventional extubation (between 8 and 12 AM the following day) (group B, 203 patients). Variables included type and severity of the disease, surgical risk, type of operation, operative incidences, postoperative complications, duration of mechanical ventilation, intubation and ICU stay, bleeding, reoperation, vasoactive drugs, and mortality. Results Groups were comparable. Extubation within the preestablished time was successful in 60.2% of patients in group A and 74.4% in group B. Median ICU stay was 27 h in group A and 44 h in group B (p=0.008). Discharge from ICU within the first 24 h postoperatively was 44.3% in group A and 30.5% in group B (p=0.006). There was no significant difference in complications between groups. Successfully extubated patients in group A had more reintubation and prolonged ventilation than in group B. Conclusions (1) Sixty percent of our patients were extubated within 11 h of operation. (2) As a result, the length of stay in ICU was reduced and the percentage of patients discharged within 24 h was increased. (3) There was no increase in clinically important postoperative complications.

Published
1997
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9. [Influence of the combination of antiplatelet agents on the occurrence of early left ventricular insufficiency in patients with acute coronary syndromes without persistent ST-segment elevation]

Author

Rafael, Blancas Gómez-Casero, Manuel, Quintana Díaz, Miriam, Chana García, Carmen, Martín Parra, Blanca, López Matamala, Belén, Estébanez Montiel, Daniel, Ballesteros Ortega, Oscar, Martínez González, Dolores, Vigil Escribano, Francisca, Prieto Valderrey, Luis, Marina Martínez, and Olmos, Castro Gallego

Subjects
Aged, 80 and over, Male, Ticlopidine, Aspirin, Middle Aged, Clopidogrel, Ventricular Dysfunction, Left, Treatment Outcome, Tirofiban, Risk Factors, Humans, Tyrosine, Drug Therapy, Combination, Female, Prospective Studies, Acute Coronary Syndrome, Platelet Aggregation Inhibitors, Aged
Abstract

The frequency of left ventricular failure (LVF) in the early stages of non-ST-segment elevation acute coronary syndrome (NSTE ACS) has not been described so far. The objective of this study is to describe for the first time the frequency of LVF in the early course of NSTE ACS and to assess its association with other interventions.Observational prospective cohort multicenter study in intensive and coronary care units (ICCU). Patients with NSTE ACS admitted within 24h after onset were included. Main outcome was the occurrence of LVF. We evaluated the association between LVF and clinical and therapeutic variables.LVF occurred in 15.6% of patients. Coronary angiography (CA) during admission to the ICCU was a protective variable against the main outcome, performed before 72h (odds ratio [OR] 0.47; 95% confidence interval [95% CI] 0.25-0.89; P=.022) and later (OR 0,39; 95% CI 0,15-0,98; P=.044). The administration of beta-blockers was a protective variable against the occurrence of LVF (OR 0,54; 95% CI 0,32-0,87; P=.013). Patients receiving acetylsalicylic acid before admission to the ICCU had a higher risk of developing LVF (OR 1.74; 95% CI 1.06-2.86; P=.028). Age was also a factor of risk for LVF (OR 1.02; 95% CI 1.00-1.05; P=.032).CA and beta-blockers can decrease the occurrence of LVF. The association between previous administration of acetylsalicylic acid and age with the occurrence of LVF may reflect long-standing cardiovascular disease.

Published
2012

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