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466 results on '"Cazorla, A"'

1. Genetic landscape of Segawa disease in Spain. Long-term treatment outcomes

Author: Matthew Martin, Katrin Beyer, Juan Luis Pérez-Navero, Eduardo López-Laso, Matias Mora, L. González Gutierrez-Solana, J. Martínez-Ruiz, J. Hernandez-Vara, M. Llorente, Á. García Cazorla, Juan-Luis Ramos, Rafael Artuch, María José de la Torre-Aguilar, J. Serrano Cárdenas, Pablo Mir, Beatriz Quintáns, M.J. Sobrido Gómez, A. Adarmes, J.J. Ochoa Sepúlveda, M.D. Teva, C. Castaño-de la Mota, J.C. Gómez-Esteban, Joaquín A. Fernández-Ramos, and E. Moreno-Medinilla
Subjects: GTPCH, Pediatrics, medicine.medical_specialty, Levodopa, Dopamine, Parkinson's disease, Decarboxylase inhibitor, Pedigree chart, Disease, Autosomal dominant Segawa disease, Parkinsonism, medicine, Humans, Founder mutation, GTP Cyclohydrolase, Adverse effect, Retrospective Studies, Dystonia, Dyskinesias, business.industry, medicine.disease, Dopa-responsive dystonia, Autosomal dominant GTPCH deficiency, Treatment Outcome, Neurology, Dystonic Disorders, Spain, Cohort, Neurology (clinical), Geriatrics and Gerontology, business, GCH1, Founder effect, medicine.drug
Abstract: Introduction In 2009, we described a possible founder effect of autosomal dominant Segawa disease in Cordoba (Spain) due to mutation c.265C>T (p. Q89*) in the GCH1 gene. We present a retrospective multicentre study aimed at improving our knowledge of Segawa disease in Spain and providing a detailed phenotypic-genotypic description of patients. Methods Clinical-genetic information were obtained from standardized questionnaires that were completed by the neurologists attending children and/or adults from 16 Spanish hospitals. Results Eighty subjects belonging to 24 pedigrees had heterozygous mutations in GCH1. Seven genetic variants have been described only in our cohort of patients, 5 of which are novel mutations. Five families not previously described with p. Q89* were detected in Andalusia due to a possible founder effect. The median latency to diagnosis was 5 years (IQR 0–16). The most frequent signs and/or symptoms were lower limb dystonia (38/56, 67.8%, p = 0.008) and diurnal fluctuations (38/56, 67.8%, p = 0.008). Diurnal fluctuations were not present in the phenotypes other than dystonia. Fifty-three of 56 symptomatic patients were treated with a levodopa/decarboxylase inhibitor for (mean ± SD) 12.4 ± 8.12 years, with 81% at doses lower than 350 mg/day (≤5 mg/kg/d in children). Eleven of 53 (20%) patients had non-responsive symptoms that affected daily life activities. Dyskinesias (4 subjects) were the most prominent adverse effects. Conclusion This study identifies 5 novel mutations and supports the hypothesis of a founder effect of p. Q89* in Andalusia. New insights are provided for the phenotypes and long-term treatment responses, which may improve early recognition and therapeutic management.
Published: 2022

2. Assessment of left ventricular dyssynchrony by speckle tracking echocardiography in children with duchenne muscular dystrophy

Author: Olivier Cazorla, Charlene Bredy, Marie Vincenti, Catherine Barrea, Albano Melli, Alain Lacampagne, Pascal Amedro, Jérémy Fauconnier, Kathleen Lavastre, Pierre Meyer, Lucie Gamon, Audrey Agullo, Nicolas Lanot, Hamouda Abassi, François Rivier, Thibault Mura, Gregoire De La Villeon, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Cliniques Universitaires Saint-Luc [Bruxelles], Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de rythmologie et modélisation cardiaque [Pessac] (IHU Liryc), Herrada, Anthony, UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, and UCL - (SLuc) Service de cardiologie pédiatrique
Subjects: Male, medicine.medical_specialty, Cardiac dyssynchrony, Adolescent, Heart Ventricles, Duchenne muscular dystrophy, Heart failure, Speckle tracking echocardiography, Ventricular Dysfunction, Left, Predictive Value of Tests, MESH: Child, Internal medicine, DMD, MESH: Ventricular Dysfunction, Left, MESH: Muscular Dystrophy, Duchenne, medicine, Humans, Radiology, Nuclear Medicine and imaging, Prospective Studies, Child, Ventricular dyssynchrony, Speckle tracking, MESH: Adolescent, MESH: Humans, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Reproducibility of Results, Paediatrics, medicine.disease, MESH: Male, MESH: Predictive Value of Tests, MESH: Prospective Studies, Muscular Dystrophy, Duchenne, MESH: Reproducibility of Results, Echocardiography, Cardiology, MESH: Echocardiography, MESH: Heart Ventricles, business, Cardiology and Cardiovascular Medicine, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Purpose-Prognosis of Duchenne muscular dystrophy (DMD) is related to cardiac dysfunction. Two dimensional-speckle tracking echocardiography (2D-STE) has recently emerged as a non-invasive functional biomarker for early detection of DMD-related cardiomyopathy. This study aimed to determine, in DMD children, the existence of a left ventricle (LV) dyssynchrony using 2D-STE analysis.Methods-This prospective controlled study enrolled 25 boys with DMD (mean age 11.0±3.5 years) with normal LV ejection fraction and 50 age-matched controls. Three measures were performed to assess LV mechanical dyssynchrony: the opposing-wall delays (longitudinal and radial analyses), the modified Yu index, and the time-to-peak delays of each segment. Feasibility and reproducibility of 2D-STE dyssynchrony were evaluated. Results-All three mechanical dyssynchrony criteria were significantly higher in the DMD group than in healthy subjects: (1) opposing-wall delays in basal inferoseptal to basal anterolateral segments (61.4±45.3 msec vs. 18.3±50.4 msec, Prespectively) and in mid inferoseptal to mid anterolateral segments (58.6±35.3 msec vs. 42.4±36.4 msec, Prespectively), (2) modified Yu index (33.3±10.1 msec vs. 28.5±8.1 msec, P, respectively), and (3) most of time-to-peak values, especially in basal and mid anterolateral segments. Feasibility was excellent and reliability was moderate to excellent, with ICC values ranging from 0.49 to 0.97.Conclusion-Detection of LV mechanical dyssynchrony using 2D-STE analysis is an easily and reproducible method in pediatrics. The existence of an early LV mechanical dyssynchrony visualized using 2D-STE analysis in children with DMD before the onset of cardiomyopathy represents a perspective for future pediatric drug trials in the DMD-related cardiomyopathy prevention. Clinical Trial Registration-Clinicaltrials.gov NCT02418338. Post-hoc study, registered on April 16, 2015.
Published: 2021

3. Cognitive stimulation has potential for brain activation in individuals with Rett syndrome

Author: Á García-Cazorla, M Pineda, Judith Armstrong, A López-Sala, Carolina Migliorelli, M D M O'Callahan, A Tost, Alejandro Bachiller, Miguel Angel Mañanas, Joan Francesc Alonso, I Medina-Rivera, Sergio Romero, Universitat Politècnica de Catalunya. Departament d'Enginyeria de Sistemes, Automàtica i Informàtica Industrial, Universitat Politècnica de Catalunya. Doctorat en Enginyeria Biomèdica, and Universitat Politècnica de Catalunya. BIOART - BIOsignal Analysis for Rehabilitation and Therapy
Subjects: medicine.medical_specialty, Brain activity and meditation, Rett, Síndrome de, Stimulation, Rett syndrome, Cognitive stimulation, Electroencephalography, Audiology, electroencephalography (EEG), Cognition, Rhythm, Arts and Humanities (miscellaneous), Rett Syndrome, medicine, Humans, Beta Rhythm, Electroencephalography (EEG), Child, Brain Symmetry Index, Eye tracking, Cognitive Behavioral Therapy, medicine.diagnostic_test, business.industry, Rehabilitation, Neuropsychology, Brain, medicine.disease, Psychiatry and Mental health, cognitive stimulation, eye-tracking, Neurology, Child, Preschool, Female, Neurology (clinical), Electroencefalografia, business, Brain symmetry index, Ciències de la salut [Àrees temàtiques de la UPC]
Abstract: Background: Knowledge regarding neuropsychological training in Rett syndrome (RS) is scarce. The aim of this study was to assess the outcome and the duration of the effect of cognitive stimulation on topographic EEG data in RS. Method: Twenty female children diagnosed with RS were included in the analysis. Girls with RS conducted a cognitive task using an eye-tracker designed to evaluate access and choice skills. EEG data was acquired during the experimental procedure including two 10-minutes baseline stages before and after the task. Topographical changes of several EEG spectral markers including absolute and relative powers, brain symmetry index and entropy were assessed. Results: Topographic significance probability maps suggested statistical decreases on delta activity and increases on beta rhythm associated with the cognitive task. Entropy increased during and after the task, likely related to more complex brain activity. A significant positive interaction was obtained between brain symmetry index (BSI) and age showing that the improvement of interhemispheric symmetry was higher in younger girls (5-10 years). Conclusions: According to our findings, significant alterations of brain rhythms were observed during and after cognitive stimulation, suggesting that cognitive stimulation may have effects on brain activity beyond the stimulation period. Finally, our promising results also showed an increased brain symmetry that was especially relevant for the younger group. This could suggest an interaction of the eye-tracking cognitive task, however, further studies in this field are needed to assess the relation between brain asymmetries and age. We would like to acknowledge specific funding support from the Spanish Patient Associations Mi Princesa Rett and Rettando al Síndrome de Rett. This project has also received funding from Torrons Vicens and the Ministry of Science and Innovation (MICINN), Spain, under contract PID2020-117751RB-I00. CIBER-BBN is an initiative of the Instituto de Salud Carlos III, Spain. A. Bachiller is a Serra Húnter Fellow. A.García-Cazorla is supported by FIS P118/00111 “Instituto de Salud Carlos III (ISCIII)” and “Fondo Europeo de desarrollo regional (FEDER)”. A. Tost has received the predoctoral scholarship FI-AGAUR from the Generalitat de Catalunya.
Published: 2021

4. Linfoma T intestinal epiteliotrópico monomórfico

Author: Jorge Nieto Orellana, Ricardo Yoncón Romero, Anthony Ochoa Bastidas, Fuad Huamán Garaicoa, Carlos Benites Ordinola, and María Paz Vintimilla Cazorla
Subjects: medicine.medical_specialty, Malabsorption, business.industry, Exploratory laparotomy, Intestinal Neoplasm, medicine.medical_treatment, Abdominal cavity, Short bowel syndrome, medicine.disease, Gastroenterology, Jejunum, Diarrhea, medicine.anatomical_structure, Oncology, Internal medicine, medicine, Histopathology, medicine.symptom, business
Abstract: Introducción: El linfoma de células T intestinal epiteliotrópico monomórfico es una neoplasia derivada de linfocitos intraepiteliales. La etiología es desconocida, pero se ha asociado a enfermedad celíaca o a síndrome de malabsorción, aunque en la actualidad se considera un linfoma esporádico. La histopatología se caracteriza por linfocitos de tamaño intermedio a pequeño, con mínimo pleomorfismo, que generalmente expresan CD8 y CD56. Reporte de caso: Mujer de 60 años con un cuadro de dispepsia de larga evolución, ingresada por dolor abdominal agudo, diarrea, nausea, vómito bilioso y pérdida de peso. En los estudios se determinó anemia microcítica hipocrómica y desequilibrio hidroelectrolítico. Se evidenció por tomografía de abdomen una lesión nodular esplénica y engrosamiento concéntrico segmentario de yeyuno e íleon distal asociado a la presencia de líquido libre en cavidad abdominal. Evolución: Se realizó una laparotomía exploratoria con resección de yeyuno-transverso anastomosis latero-lateral, en patología se deteminó la presencia de 3 tumores: a nivel de yeyuno de 16x8.5x6 cm, en el íleon distal de 13x6.5x3 cm y en el ciego de 5x4x2cm con histología de linfoma no Hodgkin T de alto grado, intestinal primario, de tipo monomórfico epiteliotrópico (MEITL). Fue dada de alta en mejores condiciones diez días después. Dos semanas luego del alta desarrollo sepsis de foco urinario, deshidratación por síndrome de intestino corto, hiperamonemia y neumonía de focos múltiples con derrame pleural bilateral. Falleció al sexto día de hospitalización. Conclusiones: En conclusión, el MEITL es una neoplasia agresiva primaria intestinal de reciente identificación y pobre pronóstico. No se conocen en su totalidad los mecanismos moleculares y genéticos asociados a esta entidad. El caso presentado demostró un curso clínico similar al reportado en la literatura.
Published: 2021

5. Prenatal diagnosis of cor triatriatum sinister associated with early pericardial effusion: A case report

Author: Duska Beric, Melanie Cristine Alonzo, Leyre Álvarez, Rebeca Jara, Esther Cánovas, and Eduardo Cazorla
Subjects: congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, Prenatal diagnosis, Pericardial effusion, 03 medical and health sciences, 0302 clinical medicine, Case report, Medicine, cardiovascular diseases, Cor triatriatum, business.industry, food and beverages, General Medicine, respiratory system, medicine.disease, respiratory tract diseases, Cor triatriatum sinister, Congenital heart defects, Echocardiography, 030220 oncology & carcinogenesis, cardiovascular system, 030211 gastroenterology & hepatology, Radiology, business
Abstract: BACKGROUND Cor triatriatum sinistrum or cor triatriatum sinister is a rare congenital heart disease that accounts for approximately 0.1% of all cardiac abnormalities. It is defined as the presence of an anomalous septum that divides the left atrium into two cavities, and in most cases, it can be asymptomatic or less frequently very severe. CASE SUMMARY A 37-year-old pregnant woman visited our hospital. In the first trimester scan, we detected signs of fluid in the pericardium (pericardial effusion) that reached the atriums. In the third trimester, an anomalous septum in the left atrium suspicious of cor triatriatum sinister was detected. Expectant management was decided, the pregnancy evolved normally and resulted in uncomplicated delivery of a healthy child. The findings in the prenatal scan were confirmed by echocardiography and the diagnosis of cor triatriatum sinister was confirmed. The newborn was asymptomatic at all times. CONCLUSION We show expectant management of cor triatriatum sinister and suggest an association between this entity and early pericardial effusion.
Published: 2021

6. Efficacy of baricitinib on chronic pericardial effusion in a patient with Aicardi–Goutières syndrome

Author: Jordi Anton, Àngels García-Cazorla, Dídac Casas-Alba, Adeline Vanderver, Thaís Armangue, Eva Caballero, Anna Mensa-Vilaro, Alejandra Darling, and J. Bartrons
Subjects: Sulfonamides, medicine.medical_specialty, business.industry, Baricitinib, Nervous System Malformations, medicine.disease, Published Online Only, Dermatology, Pericardial effusion, Pericardial Effusion, Autoimmune Diseases of the Nervous System, Rheumatology, Purines, Azetidines, Humans, Pericarditis, Pyrazoles, Medicine, Aicardi–Goutières syndrome, Pharmacology (medical), business
Published: 2021

7. Outcome of acute hypoxaemic respiratory failure: insights from the LUNG SAFE Study

Author: 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 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, 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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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, 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, 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
Subjects: 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.
Published: 2021

8. Death in hospital following ICU discharge: insights from the LUNG SAFE study

Author: Madotto F., McNicholas B., Rezoagli E., Pham T., Laffey J. G., Bellani G., Pesenti A., Brochard L., Esteban A., Gattinoni L., van Haren F., Ranieri M., Rubenfeld G., Thompson B. T., Slutsky A. S., Rios F., Faruq M. O., Sottiaux T., Depuydt P., Lora F. S., Azevedo C. C., Fan E., Bugedo G., Qiu H., Gonzalez M., Silesky J., Cerny V., Nielsen J., Jibaja M., Wrigge H., Matamis D., Ranero J. L., Gomersall C., Amin P., Hashemian S. M., Clarkson K., Kurahashi K., Koh Y., Villagomez A., Zeggwagh A. A., Heunks L. M., Laake J. H., Kashif W., Synclair J., Palo J. E., do Vale Fernandes A., Sandesc D., Arabi Y., Bumbasierevic V., Nin N., Lorente J. A., Larsson A., Piquilloud L., Patjanasoontorn B., Abroug F., McAuley D. F., McNamee L., Hurtado J., Bajwa E., Dempaire G., Francois G. M., Rabboni F., Conti S., Sula H., Nunci L., Cani A., Zazu A., Dellera C., Insaurralde C. S., Alejandro R. V., Daldin J., Vinzio M., Fernandez R. O., Cardonnet L. P., Bettini L. R., Bisso M. C., Osman E. M., Setten M. G., Lovazzano P., Alvarez J., Villar V., Pozo N. C., Grubissich N., Plotnikow G. A., Vasquez D. N., Ilutovich S., Tiribelli N., Chena A., Pellegrini C. A., Saenz M. G., Estenssoro E., Brizuela M., Gianinetto H., Gomez P. E., Cerrato V. I., Bezzi M. G., Borello S. A., Loiacono F. A., Fernandez A. M., Knowles S., Reynolds C., Inskip D. M., Miller J. J., Kong J., Whitehead C., Bihari S., Seven A., Krstevski A., Rodgers H. J., Millar R. T., Mckenna T. E., Bailey I. M., Hanlon G. C., Aneman A., Lynch J. M., Azad R., Neal J., Woods P. W., Roberts B. L., Kol M. R., Wong H. S., Riss K. C., Staudinger T., Wittebole X., Berghe C., Bulpa P. A., Dive A. M., Verstraete R., Lebbinck H., Vermassen J., Meersseman P., Ceunen H., Rosa J. I., Beraldo D. O., Piras C., Rampinelli A. M., Nassar N. P., Mataloun S., Moock M., Thompson M. M., Goncalves C. H., Antonio A. C. P., Ascoli A., Biondi R. S., Fontenele D. C., Nobrega D., Sales V. M., Shindhe S., Aiman D. M., Ismail B. P. H., Laffey J., Beloncle F., Davies K. G., Cirone R., Manoharan V., Ismail M., Goligher E. C., Jassal M., Ferguson N. D., Nishikawa E., Javeed A., Curley G., Rittayamai N., Parotto M., Mehta S., Knoll J., Pronovost A., Canestrini S., Bruhn A. R., Garcia P. H., Aliaga F. A., Farias P. A., Yumha J. S., Ortiz C. A., Salas J. E., Saez A. A., Vega L. D., Labarca E. F., Martinez F. T., Carreno N. G., Lora P., Liu H., Liu L., Tang R., Luo X., An Y., Zhao H., Gao Y., Zhai Z., Ye Z. L., Wang W., Li W., Li Q., Zheng R., Yu W., Shen J., Li X., Yu T., Lu W., Wu Y. Q., Huang X. B., He Z., Lu Y., Han H., Zhang F., Sun R., Wang H. X., Qin S. H., Zhu B. H., Zhao J., Liu J., Li B., Liu J. L., Zhou F. C., Li Q. J., Zhang X. Y., Li-Xin Z., Xin-Hua Q., Jiang L., Gao Y. N., Zhao X. Y., Li Y. Y., Li X. L., Wang C., Yao Q., Yu R., Chen K., Shao H., Qin B., Huang Q. Q., Zhu W. H., Hang A. Y., Hua M. X., Li Y., Xu Y., Di Y. D., Ling L. L., Qin T. H., Wang S. H., Qin J., Han Y., Zhou S., Vargas M. P., Jimenez J. I. S., Rojas M. A. G., 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., Klasen F., 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., Constantin J. -M., 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. A., Nichol A., Knapman K. M., O'Croinin D., Dunne E. S., Breen D. M., Clarkson K. P., Jaafar R. F., Dwyer R., Amir F., Ajetunmobi O. O., O'Muircheartaigh A. C., Black C. S., Treanor N., Collins D. V., Altaf W., Zani G., Fusari M., Spadaro S., Volta C. A., Graziani R., Brunettini B., Palmese S., Formenti P., Umbrello M., Lombardo A., Pecci E., Botteri M., Savioli M., Protti A., Mattei A., Schiavoni L., Tinnirello A., Todeschini M., Giaccone P. P., Giarratano A., Cortegiani A., Sher S., Rossi A., Antonelli M. M., Montini L. M., Casalena P., Scafetti S., Panarello G., Occhipinti G., Patroniti N., Pozzi M., Biscione R. R., Poli M. M., Raimondi F., Albiero D., Crapelli G., Beck E., Pota V., Schiavone V., Molin A., Tarantino F., Monti G., Frati E., Mirabella L., Cinnella G., Fossali T., Colombo R., Pattarino P. T. I., Mojoli F., Braschi A., Borotto E. E., Cracchiolo A. N., Palma D. M., Raponi F., Foti G., Vascotto E. R., Coppadoro A., Brazzi L., Floris L., Iotti G. A., Venti A., Yamaguchi O., Takagi S., Maeyama H. N., Watanabe E., Yamaji Y., Shimizu K., Shiozaki K., Futami S., Ryosuke S., Saito K., Kameyama Y., Ueno K., Izawa M., Okuda N., Suzuki H., Harasawa T., Nasu M., Takada T., Ito F., Nunomiya S., Koyama K., Abe T., Andoh K., Kusumoto K., Hirata A., Takaba A., Kimura H., Matsumoto S., Higashijima U., Honda H., Aoki N., Imai H., Ogino Y., Mizuguchi I., Ichikado K., Nitta K., Mochizuki K., Hashida T., Tanaka H., Nakamura T., Niimi D., Ueda T., Kashiwa Y., Uchiyama A., Sabelnikovs O., Oss P., Haddad Y., Liew K. Y., Namendys-Silva S. A., Jarquin-Badiola Y. D., Sanchez-Hurtado L. A., Gomez-Flores S. S., Marin M. C., Villagomez A. J., Lemus J. S., Fierro J. M., Cervantes M. R., Mejia F. J. F., Dector D., Dector D. M., Gonzalez D. R., Estrella C. R., Sanchez-Medina J. R., Ramirez-Gutierrez A., George F. G., Aguirre J. S., Buensuseso J. A., Poblano M., University M. V., Dendane T., Balkhi H., Elkhayari M., Samkaoui N., Ezzouine H., Benslama A., Amor M., Maazouzi W., Cimic N., Beck O., Bruns M. M., Schouten J. A., Rinia M., Raaijmakers M., Van Wezel H. M., Heines S. J., Strauch U., Buise M. P., Simonis F. D., Schultz M. J., Goodson J. C., Browne T. S., Navarra L., Hunt A., Hutchison R. A., Bailey M. B., Newby L., Mcarthur C., Kalkoff M., Mcleod A., Casement J., Hacking D. J., Andersen F. H., Dolva M. S., Barratt-Due A., Noremark K. A. L., Soreide E., Sjobo B. A., Guttormsen A. B., Yoshido H. H. L., Aguilar R. Z., Oscanoa F. A. M., Alisasis A. U., Robles J. B., Pasanting-Lim R. A. B., Tan B. C., Andruszkiewicz P., Jakubowska K., Coxo C. M., Alvarez A. M., Oliveira B. S., Montanha G. M., Barros N. C., Pereira C. S., Messias A. M., Monteiro J. M., Araujo A. M., Catorze N. T., Marum S. M., Bouw M. J., Gomes R. M., Brito V. A., Castro S., Estilita J. M., Barros F. M., Serra I. M., Martinho A. M., Tomescu D. R., Marcu A., Bedreag O. H., Papurica M., Corneci D. E., Negoita S. I., Grigoriev E., Gritsan A. I., Gazenkampf A. A., Almekhlafi G., Albarrak M. M., Mustafa G. M., Maghrabi K. A., Salahuddin N., Aisa T. M., Al Jabbary A. S., Tabhan E., Arabi Y. M., Trinidad O. A., Al Dorzi H. M., Tabhan E. E., Bolon S., Smith O., Mancebo J., Aguirre-Bermeo H., Lopez-Delgado J. C., Esteve F., Rialp G., Forteza C., De Haro C., Artigas A., Albaiceta G. M., De Cima-Iglesias S., Seoane-Quiroga L., Ceniceros-Barros A., Ruiz-Aguilar A. L., Claraco-Vega L. M., Soler J. A., del Carmen Lorente M., Hermosa C., Gordo F., Prieto-Gonzalez M., Lopez-Messa J. B., Perez M. P., Perez C. P., Allue R. M., Roche-Campo F., Ibanez-Santacruz M., Temprano S., Pintado M. C., De Pablo R., Gomez P. R. A., Ruiz S. R., Moles S. I., Jurado M. ªT., Arizmendi A., Piacentini E. A., Franco N., Honrubia T., Cheng M. P., Losada E. P., Blanco J., Yuste L. J., Carbayo-Gorriz C., Cazorla-Barranquero F. G., Alonso J. G., Alda R. S., Algaba A., Navarro G., Cereijo E., Diaz-Rodriguez E., Marcos D. P., Montero L. A., Para L. H., Sanchez R. J., Navalpotro M. A. B., Abad R. D., lez R. M. G. A., Toribio D. P., Castro A. G., Artiga M. J. D., Penuelas O., Roser T. P., Olga M. F., Curto E. G., Sanchez R. M., Imma V. P., Elisabet G. M., Claverias L., Magret M., Pellicer A. M., Rodriguez L. L., Sanchez-Ballesteros J., Gonzalez-Salamanca A., Jimenez A. G., Huerta F. P., Diaz J. C. J. S., Lopez E. B., Moya D. D. L., Alfonso A. A. T., Luis P. S. E., Cesar P. S., Rafael S. I., Virgilio C. G., Recio N. N., Adamsson R. O., Rylander C. C., Holzgraefe B., Broman L. M., Wessbergh J., Persson L., Schioler F., Kedelv H., Tibblin A. O., Appelberg H., Hedlund L., Helleberg J., Eriksson K. E., Glietsch R., Larsson N., Nygren I., Nunes S. L., Morin A. -K., Kander T., Adolfsson A., Zender H. O., Leemann-Refondini C., Elatrous S., Bouchoucha S., Chouchene I., Ouanes I., Marsa L., Souissi A. B., Kamoun S., Demirkiran O., Aker M., Erbabacan E., Ceylan I., Girgin N. K., Ozcelik M., Unal N., Meco B. C., Akyol O. O., Derman S. S., Kennedy B., Parhar K., Srinivasa L., McAuley D., Hopkins P., Mellis C., Kakar V., Hadfield D., Vercueil A., Bhowmick K., Humphreys S. K., Ferguson A., Mckee R., Raj A. S., Fawkes D. A., Watt P., Twohey L., Thomas R. R. J. M., Morton A., Kadaba V., Smith M. J., Hormis A. P., Kannan S. G., Namih M., Reschreiter H., Camsooksai J., Kumar A., Rugonfalvi S., Nutt C., Oneill O., Seasman C., Dempsey G., Scott C. J., Ellis H. E., Mckechnie S., Hutton P. J., Di Tomasso N. N., Vitale M. N., Griffin R. O., Dean M. N., Cranshaw J. H., Willett E. L., Ioannou N., Gillis S., Csabi P., Macfadyen R., Dawson H., Preez P. D., Williams A. J., Boyd O., De Gordoa L. O. -R., Bramall J., Symmonds S., Chau S. K., Wenham T., Szakmany T., Toth-Tarsoly P., Mccalman K. H., Alexander P., Stephenson L., Collyer T., Chapman R., Cooper R., Allan R. M., Sim M., Wrathall D. W., Irvine D. A., Zantua K. S., Adams J. C., Burtenshaw A. J., Sellors G. P., Welters I. D., Williams K. E., Hessell R. J., Oldroyd M. G., Battle C. E., Pillai S., Kajtor I., Sivashanmugavel M., Okane S. C., Donnelly A., Frigyik A. D., Careless J. P., May M. M., Stewart R., Trinder T. J., Hagan S. J., Wise M. P., Cole J. M., MacFie C. C., Dowling A. T., Nunez E., Pittini G., Rodriguez R., Imperio M. C., Santos C., Deicas A., Serra C., Uppalapati A., Kamel G., Banner-Goodspeed V. M., Beitler J. R., Mukkera S. R., Kulkarni S., Lee J., Mesar T., Shinn Iii J. O., Gomaa D., Tainter C., Yeatts D. J., Warren J., Lanspa M. J., Miller R. R., Grissom C. K., Brown S. M., Bauer P. R., Gosselin R. J., Kitch B. T., Cohen J. E., Beegle S. H., Gueret R. 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., Madotto, F., Mcnicholas, B., Rezoagli, E., Pham, T., Laffey, J. G., Bellani, G., Pesenti, A., Brochard, L., Esteban, A., Gattinoni, L., van Haren, F., Ranieri, M., Rubenfeld, G., Thompson, B. T., Slutsky, A. S., Rios, F., Faruq, M. O., Sottiaux, T., Depuydt, P., Lora, F. S., Azevedo, C. C., Fan, E., Bugedo, G., Qiu, H., Gonzalez, M., Silesky, J., Cerny, V., Nielsen, J., Jibaja, M., Wrigge, H., Matamis, D., Ranero, J. L., Gomersall, C., Amin, P., Hashemian, S. M., Clarkson, K., Kurahashi, K., Koh, Y., Villagomez, A., Zeggwagh, A. A., Heunks, L. M., Laake, J. H., Kashif, W., Synclair, J., Palo, J. E., do Vale Fernandes, A., Sandesc, D., Arabi, Y., Bumbasierevic, V., Nin, N., Lorente, J. A., Larsson, A., Piquilloud, L., Patjanasoontorn, B., Abroug, F., Mcauley, D. F., Mcnamee, L., Hurtado, J., Bajwa, E., Dempaire, G., Francois, G. M., Rabboni, F., Conti, S., Sula, H., Nunci, L., Cani, A., Zazu, A., Dellera, C., Insaurralde, C. S., Alejandro, R. V., Daldin, J., Vinzio, M., Fernandez, R. O., Cardonnet, L. P., Bettini, L. R., Bisso, M. C., Osman, E. M., Setten, M. G., Lovazzano, P., Alvarez, J., Villar, V., Pozo, N. C., Grubissich, N., Plotnikow, G. A., Vasquez, D. N., Ilutovich, S., Tiribelli, N., Chena, A., Pellegrini, C. A., Saenz, M. G., Estenssoro, E., Brizuela, M., Gianinetto, H., Gomez, P. E., Cerrato, V. I., Bezzi, M. G., Borello, S. A., Loiacono, F. A., Fernandez, A. M., Knowles, S., Reynolds, C., Inskip, D. M., Miller, J. J., Kong, J., Whitehead, C., Bihari, S., Seven, A., Krstevski, A., Rodgers, H. J., Millar, R. T., Mckenna, T. E., Bailey, I. M., Hanlon, G. C., Aneman, A., Lynch, J. M., Azad, R., Neal, J., Woods, P. W., Roberts, B. L., Kol, M. R., Wong, H. S., Riss, K. C., Staudinger, T., Wittebole, X., Berghe, C., Bulpa, P. A., Dive, A. M., Verstraete, R., Lebbinck, H., Vermassen, J., Meersseman, P., Ceunen, H., Rosa, J. I., Beraldo, D. O., Piras, C., Rampinelli, A. M., Nassar, N. P., Mataloun, S., Moock, M., Thompson, M. M., Goncalves, C. H., Antonio, A. C. P., Ascoli, A., Biondi, R. S., Fontenele, D. C., Nobrega, D., Sales, V. M., Shindhe, S., Aiman, D. M., Ismail, B. P. H., Laffey, J., Beloncle, F., Davies, K. G., Cirone, R., Manoharan, V., Ismail, M., Goligher, E. C., Jassal, M., Ferguson, N. D., Nishikawa, E., Javeed, A., Curley, G., Rittayamai, N., Parotto, M., Mehta, S., Knoll, J., Pronovost, A., Canestrini, S., Bruhn, A. R., Garcia, P. H., Aliaga, F. A., Farias, P. A., Yumha, J. S., Ortiz, C. A., Salas, J. E., Saez, A. A., Vega, L. D., Labarca, E. F., Martinez, F. T., Carreno, N. G., Lora, P., Liu, H., Liu, L., Tang, R., Luo, X., An, Y., Zhao, H., Gao, Y., Zhai, Z., Ye, Z. L., Wang, W., Li, W., Li, Q., Zheng, R., Yu, W., Shen, J., Li, X., Yu, T., Lu, W., Wu, Y. Q., Huang, X. B., He, Z., Lu, Y., Han, H., Zhang, F., Sun, R., Wang, H. X., Qin, S. H., Zhu, B. H., Zhao, J., Liu, J., Li, B., Liu, J. L., Zhou, F. C., Li, Q. J., Zhang, X. Y., Li-Xin, Z., Xin-Hua, Q., Jiang, L., Gao, Y. N., Zhao, X. Y., Li, Y. Y., Li, X. L., Wang, C., Yao, Q., Yu, R., Chen, K., Shao, H., Qin, B., Huang, Q. Q., Zhu, W. H., Hang, A. Y., Hua, M. X., Li, Y., Xu, Y., Di, Y. D., Ling, L. L., Qin, T. H., Wang, S. H., Qin, J., Han, Y., Zhou, S., Vargas, M. P., Jimenez, J. I. S., Rojas, M. A. G., 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., Klasen, F., 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., Constantin, J. -M., 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. A., Nichol, A., Knapman, K. M., O'Croinin, D., Dunne, E. S., Breen, D. M., Clarkson, K. P., Jaafar, R. F., Dwyer, R., Amir, F., Ajetunmobi, O. O., O'Muircheartaigh, A. C., Black, C. S., Treanor, N., Collins, D. V., Altaf, W., Zani, G., Fusari, M., Spadaro, S., Volta, C. A., Graziani, R., Brunettini, B., Palmese, S., Formenti, P., Umbrello, M., Lombardo, A., Pecci, E., Botteri, M., Savioli, M., Protti, A., Mattei, A., Schiavoni, L., Tinnirello, A., Todeschini, M., Giaccone, P. P., Giarratano, A., Cortegiani, A., Sher, S., Rossi, A., Antonelli, M. M., Montini, L. M., Casalena, P., Scafetti, S., Panarello, G., Occhipinti, G., Patroniti, N., Pozzi, M., Biscione, R. R., Poli, M. M., Raimondi, F., Albiero, D., Crapelli, G., Beck, E., Pota, V., Schiavone, V., Molin, A., Tarantino, F., Monti, G., Frati, E., Mirabella, L., Cinnella, G., Fossali, T., Colombo, R., Pattarino, P. T. I., Mojoli, F., Braschi, A., Borotto, E. E., Cracchiolo, A. N., Palma, D. M., Raponi, F., Foti, G., Vascotto, E. R., Coppadoro, A., Brazzi, L., Floris, L., Iotti, G. A., Venti, A., Yamaguchi, O., Takagi, S., Maeyama, H. N., Watanabe, E., Yamaji, Y., Shimizu, K., Shiozaki, K., Futami, S., Ryosuke, S., Saito, K., Kameyama, Y., Ueno, K., Izawa, M., Okuda, N., Suzuki, H., Harasawa, T., Nasu, M., Takada, T., Ito, F., Nunomiya, S., Koyama, K., Abe, T., Andoh, K., Kusumoto, K., Hirata, A., Takaba, A., Kimura, H., Matsumoto, S., Higashijima, U., Honda, H., Aoki, N., Imai, H., Ogino, Y., Mizuguchi, I., Ichikado, K., Nitta, K., Mochizuki, K., Hashida, T., Tanaka, H., Nakamura, T., Niimi, D., Ueda, T., Kashiwa, Y., Uchiyama, A., Sabelnikovs, O., Oss, P., Haddad, Y., Liew, K. Y., Namendys-Silva, S. A., Jarquin-Badiola, Y. D., Sanchez-Hurtado, L. A., Gomez-Flores, S. S., Marin, M. C., Villagomez, A. J., Lemus, J. S., Fierro, J. M., Cervantes, M. R., Mejia, F. J. F., Dector, D., Dector, D. M., Gonzalez, D. R., Estrella, C. R., Sanchez-Medina, J. R., Ramirez-Gutierrez, A., George, F. G., Aguirre, J. S., Buensuseso, J. A., Poblano, M., University, M. 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P., Blanco, J., Yuste, L. J., Carbayo-Gorriz, C., Cazorla-Barranquero, F. G., Alonso, J. G., Alda, R. S., Algaba, A., Navarro, G., Cereijo, E., Diaz-Rodriguez, E., Marcos, D. P., Montero, L. A., Para, L. H., Sanchez, R. J., Navalpotro, M. A. B., Abad, R. D., Lez, R. M. G. A., Toribio, D. P., Castro, A. G., Artiga, M. J. D., Penuelas, O., Roser, T. P., Olga, M. F., Curto, E. G., Sanchez, R. M., Imma, V. P., Elisabet, G. M., Claverias, L., Magret, M., Pellicer, A. M., Rodriguez, L. L., Sanchez-Ballesteros, J., Gonzalez-Salamanca, A., Jimenez, A. G., Huerta, F. P., Diaz, J. C. J. S., Lopez, E. B., Moya, D. D. L., Alfonso, A. A. T., Luis, P. S. E., Cesar, P. S., Rafael, S. I., Virgilio, C. G., Recio, N. N., Adamsson, R. O., Rylander, C. C., Holzgraefe, B., Broman, L. M., Wessbergh, J., Persson, L., Schioler, F., Kedelv, H., Tibblin, A. O., Appelberg, H., Hedlund, L., Helleberg, J., Eriksson, K. E., Glietsch, R., Larsson, N., Nygren, I., Nunes, S. L., Morin, A. -K., Kander, T., Adolfsson, A., Zender, H. O., Leemann-Refondini, C., Elatrous, S., Bouchoucha, S., Chouchene, I., Ouanes, I., Marsa, L., Souissi, A. B., Kamoun, S., Demirkiran, O., Aker, M., Erbabacan, E., Ceylan, I., Girgin, N. K., Ozcelik, M., Unal, N., Meco, B. C., Akyol, O. O., Derman, S. S., Kennedy, B., Parhar, K., Srinivasa, L., Mcauley, D., Hopkins, P., Mellis, C., Kakar, V., Hadfield, D., Vercueil, A., Bhowmick, K., Humphreys, S. K., Ferguson, A., Mckee, R., Raj, A. S., Fawkes, D. A., Watt, P., Twohey, L., Thomas, R. R. J. M., Morton, A., Kadaba, V., Smith, M. J., Hormis, A. P., Kannan, S. G., Namih, M., Reschreiter, H., Camsooksai, J., Kumar, A., Rugonfalvi, S., Nutt, C., Oneill, O., Seasman, C., Dempsey, G., Scott, C. J., Ellis, H. E., Mckechnie, S., Hutton, P. J., Di Tomasso, N. N., Vitale, M. N., Griffin, R. O., Dean, M. N., Cranshaw, J. H., Willett, E. L., Ioannou, N., Gillis, S., Csabi, P., Macfadyen, R., Dawson, H., Preez, P. D., Williams, A. J., Boyd, O., De Gordoa, L. O. -R., Bramall, J., Symmonds, S., Chau, S. K., Wenham, T., Szakmany, T., Toth-Tarsoly, P., Mccalman, K. H., Alexander, P., Stephenson, L., Collyer, T., Chapman, R., Cooper, R., Allan, R. M., Sim, M., Wrathall, D. W., Irvine, D. A., Zantua, K. S., Adams, J. C., Burtenshaw, A. J., Sellors, G. P., Welters, I. D., Williams, K. E., Hessell, R. J., Oldroyd, M. G., Battle, C. E., Pillai, S., Kajtor, I., Sivashanmugavel, M., Okane, S. C., Donnelly, A., Frigyik, A. D., Careless, J. P., May, M. M., Stewart, R., Trinder, T. J., Hagan, S. J., Wise, M. P., Cole, J. M., Macfie, C. C., Dowling, A. T., Nunez, E., Pittini, G., Rodriguez, R., Imperio, M. C., Santos, C., Deicas, A., Serra, C., Uppalapati, A., Kamel, G., Banner-Goodspeed, V. M., Beitler, J. R., Mukkera, S. R., Kulkarni, S., Lee, J., Mesar, T., Shinn Iii, J. O., Gomaa, D., Tainter, C., Yeatts, D. J., Warren, J., Lanspa, M. J., Miller, R. R., Grissom, C. K., Brown, S. M., Bauer, P. R., Gosselin, R. J., Kitch, B. T., Cohen, J. E., Beegle, S. H., Gueret, R. 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, Investigators, LUNG SAFE, Group, ESICM Trials, Madotto, F, Mcnicholas, B, Rezoagli, E, Pham, T, Laffey, J, Bellani, G, Pesenti, A, Brochard, L, Esteban, A, Gattinoni, L, van Haren, F, Ranieri, M, Rubenfeld, G, Thompson, B, Slutsky, A, Rios, F, Faruq, M, Sottiaux, T, Depuydt, P, Lora, F, Azevedo, C, Fan, E, Bugedo, G, Qiu, H, Gonzalez, M, Silesky, J, Cerny, V, Nielsen, J, Jibaja, M, Wrigge, H, Matamis, D, Ranero, J, Gomersall, C, Amin, P, Hashemian, S, Clarkson, K, Kurahashi, K, Koh, Y, Villagomez, A, Zeggwagh, A, Heunks, L, Laake, J, Kashif, W, Synclair, J, Palo, J, do Vale Fernandes, A, Sandesc, D, Arabi, Y, Bumbasierevic, V, Nin, N, Lorente, J, Larsson, A, Piquilloud, L, Patjanasoontorn, B, Abroug, F, Mcauley, D, Mcnamee, L, Hurtado, J, Bajwa, E, Dempaire, G, Francois, G, Rabboni, F, Conti, S, Sula, H, Nunci, L, Cani, A, Zazu, A, Dellera, C, Insaurralde, C, Alejandro, R, Daldin, J, Vinzio, M, Fernandez, R, Cardonnet, L, Bettini, L, Bisso, M, Osman, E, Setten, M, Lovazzano, P, Alvarez, J, Villar, V, Pozo, N, Grubissich, N, Plotnikow, G, Vasquez, D, Ilutovich, S, Tiribelli, N, Chena, A, Pellegrini, C, Saenz, M, Estenssoro, E, Brizuela, M, Gianinetto, H, Gomez, P, Cerrato, V, Bezzi, M, Borello, S, Loiacono, F, Fernandez, A, Knowles, S, Reynolds, C, Inskip, D, Miller, J, Kong, J, Whitehead, C, Bihari, S, Seven, A, Krstevski, A, Rodgers, H, Millar, R, Mckenna, T, Bailey, I, Hanlon, G, Aneman, A, Lynch, J, Azad, R, Neal, J, Woods, P, Roberts, B, Kol, M, Wong, H, Riss, K, Staudinger, T, Wittebole, X, Berghe, C, Bulpa, P, Dive, A, Verstraete, R, Lebbinck, H, Vermassen, J, Meersseman, P, Ceunen, H, Rosa, J, Beraldo, D, Piras, C, Rampinelli, A, Nassar, N, Mataloun, S, Moock, M, Thompson, M, Goncalves, C, Antonio, A, Ascoli, A, Biondi, R, Fontenele, D, Nobrega, D, 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Poli, M, Raimondi, F, Albiero, D, Crapelli, G, Beck, E, Pota, V, Schiavone, V, Molin, A, Tarantino, F, Monti, G, Frati, E, Mirabella, L, Cinnella, G, Fossali, T, Colombo, R, Pattarino, P, Mojoli, F, Braschi, A, Borotto, E, Cracchiolo, A, Palma, D, Raponi, F, Foti, G, Vascotto, E, Coppadoro, A, Brazzi, L, Floris, L, Iotti, G, Venti, A, Yamaguchi, O, Takagi, S, Maeyama, H, Watanabe, E, Yamaji, Y, Shimizu, K, Shiozaki, K, Futami, S, Ryosuke, S, Saito, K, Kameyama, Y, Ueno, K, Izawa, M, Okuda, N, Suzuki, H, Harasawa, T, Nasu, M, Takada, T, Ito, F, Nunomiya, S, Koyama, K, Abe, T, Andoh, K, Kusumoto, K, Hirata, A, Takaba, A, Kimura, H, Matsumoto, S, Higashijima, U, Honda, H, Aoki, N, Imai, H, Ogino, Y, Mizuguchi, I, Ichikado, K, Nitta, K, Mochizuki, K, Hashida, T, Tanaka, H, Nakamura, T, Niimi, D, Ueda, T, Kashiwa, Y, Uchiyama, A, Sabelnikovs, O, Oss, P, Haddad, Y, Liew, K, Namendys-Silva, S, Jarquin-Badiola, Y, Sanchez-Hurtado, L, Gomez-Flores, S, Marin, M, Lemus, J, Fierro, J, Cervantes, M, Mejia, F, Dector, D, Gonzalez, D, Estrella, C, Sanchez-Medina, J, Ramirez-Gutierrez, A, George, F, Aguirre, J, Buensuseso, J, Poblano, M, University, M, Dendane, T, Balkhi, H, Elkhayari, M, Samkaoui, N, Ezzouine, H, Benslama, A, Amor, M, Maazouzi, W, Cimic, N, Beck, O, Bruns, M, Schouten, J, Rinia, M, Raaijmakers, M, Van Wezel, H, Heines, S, Strauch, U, Buise, M, Simonis, F, Schultz, M, Goodson, J, Browne, T, Navarra, L, Hunt, A, Hutchison, R, Bailey, M, Newby, L, Mcarthur, C, Kalkoff, M, Mcleod, A, Casement, J, Hacking, D, Andersen, F, Dolva, M, Barratt-Due, A, Noremark, K, Soreide, E, Sjobo, B, Guttormsen, A, Yoshido, H, Aguilar, R, Oscanoa, F, Alisasis, A, Robles, J, Pasanting-Lim, R, Tan, B, Andruszkiewicz, P, Jakubowska, K, Coxo, C, Alvarez, A, Oliveira, B, Montanha, G, Barros, N, Pereira, C, Messias, A, Monteiro, J, Araujo, A, Catorze, N, Marum, S, Bouw, M, Gomes, R, Brito, V, Castro, S, Estilita, J, Barros, F, Serra, I, Martinho, A, Tomescu, D, Marcu, A, Bedreag, O, Papurica, M, Corneci, D, Negoita, S, Grigoriev, E, Gritsan, A, Gazenkampf, A, Almekhlafi, G, Albarrak, M, Mustafa, G, Maghrabi, K, Salahuddin, N, Aisa, T, Al Jabbary, A, Tabhan, E, Trinidad, O, Al Dorzi, H, Bolon, S, Smith, O, Mancebo, J, Aguirre-Bermeo, H, Lopez-Delgado, J, Esteve, F, Rialp, G, Forteza, C, De Haro, C, Artigas, A, Albaiceta, G, De Cima-Iglesias, S, Seoane-Quiroga, L, Ceniceros-Barros, A, Ruiz-Aguilar, A, Claraco-Vega, L, Soler, J, del Carmen Lorente, M, Hermosa, C, Gordo, F, Prieto-Gonzalez, M, Lopez-Messa, J, Perez, M, Perez, C, Allue, R, Roche-Campo, F, Ibanez-Santacruz, M, Temprano, S, Pintado, M, De Pablo, R, Ruiz, S, Moles, S, Jurado, M, Arizmendi, A, Piacentini, E, Franco, N, Honrubia, T, Cheng, M, Losada, E, Blanco, J, Yuste, L, Carbayo-Gorriz, C, Cazorla-Barranquero, F, Alonso, J, Alda, R, Algaba, A, Navarro, G, Cereijo, E, Diaz-Rodriguez, E, Marcos, D, Montero, L, Para, L, Sanchez, R, Navalpotro, M, Abad, R, Lez, R, Toribio, D, Castro, A, Artiga, M, Penuelas, O, Roser, 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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, 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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, Mohammed V University, 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, 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, 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, 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, Lise Piquilloud, Hervé O Zender, Corinne Leemann-Refondini, Souheil Elatrous, Slaheddine Bouchoucha, Imed Chouchene, Islem Ouanes, La Marsa, 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 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 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, Matt P Wise, 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, 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 Iii, Dina Gomaa, Christopher Tainter, Jarone Lee, Tomaz Mesar, Jarone 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, 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, Daniel R Crouch, Dina Ismail, Kyle R Dreyer, Thomas C Blakeman, Kyle R Dreyer, Dina Gomaa, 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, John G Laffey, Giacomo Bellani, Antonio Pesenti
Subjects: Male, ARDS, LUNG SAFE, health care facilities, manpower, and services, Acute hypoxemic respiratory failure, Acute respiratory distress syndrome, Hospital survival, ICU discharge, Kaplan-Meier Estimate, Critical Care and Intensive Care Medicine, 0302 clinical medicine, Risk Factors, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, COPD, Medical emergencies. Critical care. Intensive care. First aid, Middle Aged, Patient Discharge, Intensive Care Units, medicine.anatomical_structure, Lung safe, SOFA score, Female, Respiratory Insufficiency, Adult, medicine.medical_specialty, NO, 03 medical and health sciences, Settore MED/41 - ANESTESIOLOGIA, medicine, Humans, ddc:610, Risk factor, Mortality, Aged, Lung, RC86-88.9, business.industry, Research, 030208 emergency & critical care medicine, medicine.disease, Logistic Models, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Respiratory failure, Emergency medicine, Observational study, business
Abstract: Background To determine the frequency of, and factors associated with, death in hospital following ICU discharge to the ward. Methods The Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE study was an international, multicenter, prospective cohort study of patients with severe respiratory failure, conducted across 459 ICUs from 50 countries globally. This study aimed to understand the frequency and factors associated with death in hospital in patients who survived their ICU stay. We examined outcomes in the subpopulation discharged with no limitations of life sustaining treatments (‘treatment limitations’), and the subpopulations with treatment limitations. Results 2186 (94%) patients with no treatment limitations discharged from ICU survived, while 142 (6%) died in hospital. 118 (61%) of patients with treatment limitations survived while 77 (39%) patients died in hospital. Patients without treatment limitations that died in hospital after ICU discharge were older, more likely to have COPD, immunocompromise or chronic renal failure, less likely to have trauma as a risk factor for ARDS. Patients that died post ICU discharge were less likely to receive neuromuscular blockade, or to receive any adjunctive measure, and had a higher pre- ICU discharge non-pulmonary SOFA score. A similar pattern was seen in patients with treatment limitations that died in hospital following ICU discharge. Conclusions A significant proportion of patients die in hospital following discharge from ICU, with higher mortality in patients with limitations of life-sustaining treatments in place. Non-survivors had higher systemic illness severity scores at ICU discharge than survivors. Trial Registration: ClinicalTrials.gov NCT02010073.
Published: 2021

9. Abstract PS3-11: Correlation of pathological complete response and radiological response with Contrast-enhanced mammography in breast cancer patients after neoadjuvant chemotherapy

Author: Ana Alicia Tejera Hernández, Manuel Cazorla Betancor, Mónica Cejuela Solís, Elena Vicente Rubio, Avinash Ramchandani Vaswani, Jose Lopez, Concepción Jiménez Medina, Pedro Pérez Correa, Paula Junquera Rionda, Isabel Reyes Rodriguez, Marta Pavcovich, Alfonso Gómez de Liaño, Maria Eugenia Galan Garcia, Elisenda Llabrés Valenti, Joel Joselito Aranda Sánchez, and Víctor Vega Benítez
Subjects: Cancer Research, Chemotherapy, medicine.medical_specialty, medicine.diagnostic_test, business.industry, medicine.medical_treatment, media_common.quotation_subject, medicine.disease, Correlation, Breast cancer, Oncology, Radiological weapon, medicine, Contrast (vision), Mammography, Radiology, business, Pathological, Complete response, media_common
Abstract: Background: Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) has been reported as a surrogate endpoint for prediction of disease-free survival (DFS) and overall survival (OS) particularly in HER2-positive and triple-negative (TN) breast cancer. NAC requires imaging techniques to accurately predict pathological response and subsequently surgical planning. Magnetic resonance imaging (MRI) has been the most sensitive technique to assess response to NAC, although it is expensive and time consuming. In our hospital we use Contrast-enhanced mammography (CEM) that is easy to perform, fast, reproducible and its signs are superimposable to the MRI, with the advantages of lower cost. It allows diagnosing multifocal, multicenter and bilateral involvement, and monitoring the response to treatment with NAC.Aims: Analyze the correlation between complete radiological response (rRC) with CEM and pCR in patients treated with NAC. Analyze this correlation based on the different immunophenotypes (IF)Methods: Retrospective analysis of 112 patients with stage II-III breast cancer treated with NAC, from January 2018 to April 2020, in the Complejo Hospitalario Universitario Insular-Materno Infantil de Gran Canaria, with CEM performed before and after NAC. pCR categorization using the Miller and Payne system, defined pCR as a non-invasive tumor in the breast and axilla (ypT0/is N0).Results: Of 112 analyzed patients, 8 did not undergo surgery (6 patients with T4d tumors received radical radiotherapy, 1 progressed during NAC and 1 did not undergo surgery for liver failure). Median age 53 years (range 31-89). Stages: IIA 26%, IIB 47%, IIIA 16%, IIIB 10%, IIIC 1%. IF: Luminal A: 11%, Luminal B Her2-: 33%, Luminal B Her2 +: 23%, pure HER2: 21%, TN: 12%. NAC received: doxorubicin-cyclophosphamide (AC)-weekly paclitaxel 53%, Taxanes + pertuzumab + trastuzumab (PT) 39%, AC-paclitaxel + PT 4%, other 4%. 99 patients obtained radiological response: 60 (54%) rRC and 39 (35%) partial response. In 14 patients (12%) there was no response. 36% pCR (N = 37). The sensitivity (S) and specificity (E) of CEM for the evaluation of pCR were 67% and 95% respectively. S was 100% in pure HER2 and 78% in TN. The positive and negative predictive values (PPV and NPV) were 96% and 61% respectively. After a median follow-up of 19 months, 6 patients have relapsed and 2 have died.Conclusion: CSEM has an S and E to detect pCR after NAC of 67 and 95% respectively; rates higher than those offered in other series by the MRI. S and E are higher in pure HER2 and TN tumors. Citation Format: Elisenda Llabrés Valentí, Jose Carlos Antela López, Mónica Cejuela Solís, Alfonso Gómez de Liaño, Victor Vega Benítez, Marta Pavcovich, Concepción Jimenez Medina, Joel Joselito Aranda Sánchez, Isabel Reyes Rodriguez, Manuel Cazorla Betancor, Maria Eugenia Galan Garcia, Ana Alicia Tejera Hernández, Pedro Pérez Correa, Paula Junquera Rionda, Avinash Ramchandani Vaswani, Elena Vicente Rubio. Correlation of pathological complete response and radiological response with Contrast-enhanced mammography in breast cancer patients after neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS3-11.
Published: 2021

10. Telomere length dynamics over 10-years and related outcomes in patients with COPD

Author: D Mayato, Elizabeth Córdoba-Lanús, F Gonzalvo, Sara Cazorla-Rivero, J Ayra-Plasencia, Ciro Casanova, M A Garcia-Bello, and Bartolome R. Celli
Subjects: 0301 basic medicine, BODE index, Adult, Male, medicine.medical_specialty, Aging, Time Factors, Lung-function, Disease, 03 medical and health sciences, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Internal medicine, medicine, Humans, COPD, In patient, Prospective Studies, Mortality, Prospective cohort study, Lung function, Telomere Shortening, Aged, lcsh:RC705-779, business.industry, Research, Smoking, lcsh:Diseases of the respiratory system, Middle Aged, Telomere, medicine.disease, Peripheral blood, 030104 developmental biology, Cross-Sectional Studies, Telomeres, 030228 respiratory system, Case-Control Studies, Cardiology, Disease Progression, Female, business, Follow-Up Studies
Abstract: Background Chronic obstructive pulmonary disease (COPD) has been proposed as a disease of accelerated aging. Several cross-sectional studies have related a shorter telomere length (TL), a marker of biological aging, with COPD outcomes. Whether accelerated telomere shortening over time relates to worse outcomes in COPD patients, is not known. Methods Relative telomere length (T/S) was determined by qPCR in DNA samples from peripheral blood in 263 patients at baseline and up to 10 years post enrolment. Yearly clinical and lung function data of 134 patients with at least two-time measures of T/S over this time were included in the analysis. Results At baseline, T/S inversely correlated with age (r = − 0.236; p 0.05). Over 10 years of observation, there was a median shortening of TL of 183 bp/year for COPD patients. After adjusting for age, gender, active smoking and mean T/S, patients that shortened their telomeres the most over time, had worse gas exchange, more lung hyperinflation and extrapulmonary affection during the follow-up, (PaO2 p CO p = 0.042; IC/TLC p Conclusions This prospective study shows an association between accelerated telomere shortening and progressive worsening of pulmonary gas exchange, lung hyperinflation and extrapulmonary affection in COPD patients. Moreover, persistently shorter telomeres over this observation time increase the risk for all-cause mortality.
Published: 2021

11. BRIP1, a Gene Potentially Implicated in Familial Colorectal Cancer Type X

Author: Patricia Llovet, Vanesa García-Barberán, Víctor Lorca, Maria Luisa Gonzalez-Morales, Marta Cazorla, Lorena Martín-Morales, Clara Esteban-Jurado, Pilar Garre, Inmaculada Bando, Trinidad Caldés, Sergi Castellví-Bel, and Miguel de la Hoya
Subjects: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Familial Colorectal Cancer Type X, Colorectal cancer, business.industry, Genetic counseling, BRIP1, Disease, Molecular diagnostics, medicine.disease, Frameshift mutation, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, medicine, business, Ovarian cancer
Abstract: Familial colorectal cancer Type X (FCCTX) comprises a heterogeneous group of families with an increased risk of developing colorectal cancer and other related tumors, but with mismatch repair–proficient, microsatellite-stable (MSS) tumors. Unfortunately, the genetic basis underlying their cancer predisposition remains unknown. Although pathogenic germline variants in BRIP1 increase the risk of developing hereditary ovarian cancer, the involvement of BRIP1 in hereditary colorectal cancer is still not well known. In order to identify new BRIP1 variants associated with inherited colorectal cancer, affected and nonaffected individuals from 18 FCCTX or high-risk MSS colorectal cancer families were evaluated by whole-exome sequencing, and another 62 colorectal cancer patients from FCCTX or high-risk MSS colorectal cancer families were screened by a next-generation sequencing (NGS) multigene panel. The families were recruited at the Genetic Counseling Unit of Hospital Clínico San Carlos of Madrid. A total of three different BRIP1 mutations in three unrelated families were identified. Among them, there were two frameshift variants [c.1702_1703del, p.(Asn568TrpfsTer9) and c.903del, p.(Leu301PhefsTer2)] that result in the truncation of the protein and are thus classified as pathogenic (class 5). The remaining was a missense variant [c.2220G>T, p.(Gln740His)] considered a variant of uncertain significance (class 3). The segregation and loss-of-heterozygosity studies provide evidence linking the two BRIP1 frameshift variants to colorectal cancer risk, with suggestive but not definitive evidence that the third variant may be benign. The results here presented suggest that germline BRIP1 pathogenic variants could be associated with hereditary colorectal cancer predisposition. Prevention Relevance: We suggest that BRIP1 pathogenic germline variants may have a causal role in CRC as moderate cancer susceptibility alleles and be associated with hereditary CRC predisposition. A better understanding of hereditary CRC may provide important clues to disease predisposition and could contribute to molecular diagnostics, improved risk stratification, and targeted therapeutic strategies.
Published: 2021

12. De novo small deletion affecting transcription start site of short isoform of <scp> AUTS2 </scp> gene in a patient with syndromic neurodevelopmental defects

Author: Emiliano Gonzalez-Vioque, Carlos Rodríguez-Martín, Pablo Tutor, Julián Lara-Herguedas, Javier Alonso, Beatriz Baladron, Eva Bermejo-Sánchez, Alejandra Damian, Irene Gonzalo, Isabel Cuesta, Enriqueta Roman, C. Jimenez, Virginia Aquino, Sara Monzón, Manuel Posada, Susana Mellor, Estrella Lopez-Martin, Purificacion Ros, Maria Jose Cabrejas, Gema Gomez-Mariano, Rosario Cazorla, Gema Iglesias, Miguel Juliá, and Beatriz Martinez-Delgado
Subjects: Gene isoform, Genetics, Biology, medicine.disease, Phenotype, Exon, Neurodevelopmental disorder, Intellectual disability, Gene expression, medicine, Copy-number variation, Gene, Genetics (clinical)
Abstract: Disruption of the autism susceptibility candidate 2 (AUTS2) gene through genomic rearrangements, copy number variations (CNVs), and intragenic deletions and mutations, has been recurrently involved in syndromic forms of developmental delay and intellectual disability, known as AUTS2 syndrome. The AUTS2 gene plays an important role in regulation of neuronal migration, and when altered, associates with a variable phenotype from severely to mildly affected patients. The more severe phenotypes significantly correlate with the presence of defects affecting the C-terminus part of the gene. This article reports a new patient with a syndromic neurodevelopmental disorder, who presents a deletion of 30 nucleotides in the exon 9 of the AUTS2 gene. Importantly, this deletion includes the transcription start site for the AUTS2 short transcript isoform, which has an important role in brain development. Gene expression analysis of AUTS2 full-length and short isoforms revealed that the deletion found in this patient causes a remarkable reduction in the expression level, not only of the short isoform, but also of the full AUTS2 transcripts. This report adds more evidence for the role of mutated AUTS2 short transcripts in the development of a severe phenotype in the AUTS2 syndrome.
Published: 2020

13. Renal microvascular oxygen tension during hyperoxia and acute hemodilution assessed by phosphorescence quenching and excitation with blue and red light

Author: Melina P Cazorla-Bak, C. David Mazer, Julie Yu, Gregory M. T. Hare, Elaine Liu, Sergei A. Vinogradov, Roger G. Evans, David F. Wilson, Richard E. Gilbert, Yanling Zhang, Kyle Chin, Kim A. Connelly, Andrew J. Baker, and Linda Nghiem
Subjects: 0301 basic medicine, Hyperoxia, Kidney, medicine.medical_specialty, business.industry, Renal cortex, Acute kidney injury, General Medicine, 030204 cardiovascular system & hematology, Hypoxia (medical), medicine.disease, Oxygen tension, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Anesthesiology and Pain Medicine, medicine.anatomical_structure, Blood pressure, Internal medicine, Anesthesia, medicine, Cardiology, Arterial blood, medicine.symptom, business
Abstract: The kidney plays a central physiologic role as an oxygen sensor. Nevertheless, the direct mechanism by which this occurs is incompletely understood. We measured renal microvascular partial pressure of oxygen (PkO2) to determine the impact of clinically relevant conditions that acutely change PkO2 including hyperoxia and hemodilution. We utilized two-wavelength excitation (red and blue spectrum) of the intravascular phosphorescent oxygen sensitive probe Oxyphor PdG4 to measure renal tissue PO2 in anesthetized rats (2% isoflurane, n = 6) under two conditions of altered arterial blood oxygen content (CaO2): 1) hyperoxia (fractional inspired oxygen 21%, 30%, and 50%) and 2) acute hemodilutional anemia (baseline, 25% and 50% acute hemodilution). The mean arterial blood pressure (MAP), rectal temperature, arterial blood gases (ABGs), and chemistry (radiometer) were measured under each condition. Blue and red light enabled measurement of PkO2 in the superficial renal cortex and deeper cortical and medullary tissue, respectively. PkO2 was higher in the superficial renal cortex (~ 60 mmHg, blue light) relative to the deeper renal cortex and outer medulla (~ 45 mmHg, red light). Hyperoxia resulted in a proportional increase in PkO2 values while hemodilution decreased microvascular PkO2 in a linear manner in both superficial and deeper regions of the kidney. In both cases (blue and red light), PkO2 correlated with CaO2 but not with MAP. The observed linear relationship between CaO2 and PkO2 shows the biological function of the kidney as a quantitative sensor of anemic hypoxia and hyperoxia. A better understanding of the impact of changes in PkO2 may inform clinical practices to improve renal oxygen delivery and prevent acute kidney injury.
Published: 2020

14. Significant Decrease in Annual Cancer Diagnoses in Spain during the COVID-19 Pandemic: A Real-Data Study

Author: Esperanza Torres, Emilio Alba, M. Cobo, Inmaculada Ramos, Ana Godoy, Laura Galvez, Nuria Ribelles, Sofia Ruiz-Medina, Begoña Jimenez, Marta Muñoz-Ayllon, Pablo Rodriguez-Brazzarola, Mireya Cazorla, María José Bermejo, Tamara Diaz-Redondo, Antonio Rueda, Carmen Reyna, Silvia Gil, [Ruiz-Medina,S, Gil,S, Jimenez,B, Diaz-Redondo,T, Cazorla,M, Muñoz-Ayllon,M, Ramos,I, Reyna,C, Bermejo,MJ, Godoy,A, Torres,E, Cobo,M, Galvez,L, Rueda,A, Alba,E, and Ribelles,N] Medical Oncology Intercenter Unit, Regional and Virgen de la Victoria University Hospitals, IBIMA, Málaga, Spain. [Rodriguez-Brazzarola,P] Grupo de Inteligencia Computacional en Biomedicina, ETSI Ingeniería Informática, Universidad de Málaga, Málaga, Spain.
Subjects: Cancer Research, Pediatrics, medicine.medical_specialty, Diseases::Neoplasms::Neoplasms by Site::Head and Neck Neoplasms [Medical Subject Headings], Coronavirus disease 2019 (COVID-19), Infecciones por coronavirus, COVID-19 pandemic, Article, 03 medical and health sciences, cancer diagnoses, 0302 clinical medicine, Breast cancer, Pandemic, medicine, 030212 general & internal medicine, Medical diagnosis, Pathological, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], RC254-282, Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings], Pandemia, SARS-CoV-2, business.industry, COVID-19, Health Care::Environment and Public Health::Public Health::Disease Outbreaks::Epidemics::Pandemics [Medical Subject Headings], Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Cancer, Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [Medical Subject Headings], medicine.disease, Neoplasias, Diseases::Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [Medical Subject Headings], Hospital care, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cross-Sectional Studies [Medical Subject Headings], Oncology, 030220 oncology & carcinogenesis, Population study, business, real data
Abstract: The COVID-19 pandemic has caused a profound change in health organizations at both the primary and hospital care levels. This cross-sectional study aims to investigate the impact of the COVID-19 pandemic in the annual rate of new cancer diagnosis in two university-affiliated hospitals. This study includes all the patients with a pathological diagnosis of cancer attended in two hospitals in Málaga (Spain) during the first year of pandemic. This study population was compared with the patients diagnosed during the previous year 2019. To analyze whether the possible differences in the annual rate of diagnoses were due to the pandemic or to other causes, the patients diagnosed during 2018 and 2017 were also compared. There were 2340 new cancer diagnosis compared to 2825 patients in 2019 which represented a decrease of −17.2% (p = 0.0001). Differences in the number of cancer patients diagnosed between 2018 and 2019 (2840 new cases, 0.5% increase) or 2017 and 2019 (2909 new cases, 3% increase) were not statistically significant. The highest number of patients lost from diagnosis in 2020 was in breast cancer (−26.1%), colorectal neoplasms (−16.9%), and head and neck tumors (−19.8%). The study of incidence rates throughout the first year of the COVID-19 pandemic shows that the diagnosis of new cancer patients has been significantly impaired. Health systems must take the necessary measures to restore pre-pandemic diagnostic procedures and to recover lost patients who have not been diagnosed.
Published: 2021

15. Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome: Insights from the LUNG SAFE study

Author: 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
Subjects: 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
Published: 2020

16. Resolved versus confirmed ARDS after 24 h: insights from the LUNG SAFE study

Author: Madotto, F., Pham, T., Bellani, G., Bos, L. D., Simonis, F. D., Fan, E., Artigas, A., Brochard, L., Schultz, M. J., Laffey, J. G., Pesenti, A., Esteban, A., Gattinoni, L., van Haren, F., Larsson, A., McAuley, D. F., Ranieri, M., Rubenfeld, G., Thompson, B. T., Wrigge, H., Slutsky, A. S., Rios, F., Van Haren, F., Sottiaux, T., Depuydt, P., Lora, F. S., Azevedo, L. C., Bugedo, G., Qiu, H., Gonzalez, M., Silesky, J., Cerny, V., Nielsen, J., Jibaja, M., Matamis, D., Ranero, J. L., Amin, P., Hashemian, S. M., Clarkson, K., Kurahashi, K., Villagomez, A., Zeggwagh, A. A., Heunks, L. M., Laake, J. H., Palo, J. E., do Vale Fernandes, A., Sandesc, D., Arabi, Y., Bumbasierevic, V., Nin, N., Lorente, J. A., Piquilloud, L., Abroug, F., McNamee, L., Hurtado, J., Bajwa, E., Démpaire, G., Sula, H., Nunci, L., Cani, A., Zazu, A., Dellera, C., Alejandro, R. V., Daldin, J., Vinzio, M., Fernandez, R. O., Cardonnet, L. P., Bettini, L. R., Bisso, M. C., Osman, E. M., Setten, M. G., Lovazzano, P., Alvarez, J., Villar, V., Pozo, N. C., Grubissich, N., Plotnikow, G. A., Vasquez, D. N., Ilutovich, S., Tiribelli, N., Chena, A., Pellegrini, C. A., Saenz, M. G., Estenssoro, E., Brizuela, M., Gianinetto, H., Gomez, P. E., Cerrato, V. I., Bezzi, M. G., Borello, S. A., Loiacono, F. A., Fernandez, A. M., Knowles, S., Reynolds, C., Inskip, D. M., Miller, J. J., Kong, J., Whitehead, C., Bihari, S., Seven, A., Krstevski, A., Rodgers, H. J., Millar, R. T., Mckenna, T. E., Bailey, I. M., Hanlon, G. C., Aneman, A., Lynch, J. M., Azad, R., Neal, J., Woods, P. W., Roberts, B. L., Kol, M. R., Wong, H. S., Riss, K. C., Staudinger, T., Wittebole, X., Berghe, C., Bulpa, P. A., Dive, A. M., Verstraete, R., Lebbinck, H., Vermassen, J., Meersseman, P., Ceunen, H., Rosa, J. I., Beraldo, D. O., Piras, C., Rampinelli, A. M., Nassar A. P., Jr., Mataloun, S., Moock, M., Thompson, M. M., Gonçalves, C. H., Antônio, A. C. P., Ascoli, A., Biondi, R. S., Fontenele, D. C., Nobrega, D., Sales, V. M., Shindhe, S., Ismail, D. M. A. B. P. H., Laffey, J., Beloncle, F., Davies, K. G., Cirone, R., Manoharan, V., Ismail, M., Goligher, E. C., Jassal, M., Nishikawa, E., Javeed, A., Curley, G., Rittayamai, N., Parotto, M., Ferguson, N. D., Mehta, S., Knoll, J., Pronovost, A., Canestrini, S., Bruhn, A. R., Garcia, P. H., Aliaga, F. A., Farías, P. A., Yumha, J. S., Ortiz, C. A., Salas, J. E., Saez, A. A., Vega, L. D., Labarca, E. F., Martinez, F. T., Carreño, N. G., Lora, P., Liu, H., Liu, L., Tang, R., Luo, X., An, Y., Zhao, H., Gao, Y., Zhai, Z., Ye, Z. L., Wang, W., Li, W., Li, Q., Zheng, R., Yu, W., Shen, J., Li, X., Yu, T., Lu, W., Wu, Y. Q., Huang, X. B., He, Z., Lu, Y., Han, H., Zhang, F., Sun, R., Wang, H. X., Qin, S. H., Zhu, B. H., Zhao, J., Liu, J., Li, B., Liu, J. L., Zhou, F. C., Li, Q. J., Zhang, X. Y., Li-Xin, Z., Xin-Hua, Q., Jiang, L., Gao, Y. N., Zhao, X. Y., Li, Y. Y., Li, X. L., Wang, C., Yao, Q., Yu, R., Chen, K., Shao, H., Qin, B., Huang, Q. Q., Zhu, W. H., Hang, A. Y., Hua, M. X., Li, Y., Xu, Y., Di, Y. D., Ling, L. L., Qin, T. H., Wang, S. H., Qin, J., Han, Y., Zhou, S., Vargas, M. P., Jimenez, J. I. S., Rojas, M. A. G., Solis-Quesada, J. E., Ramirez-Alfaro, C. M., Máca, 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., Roux, D., Messika, J., Kalaitzis, E., Dangers, L., Combes, A., Au, S. -M., Béduneau, G., Carpentier, D., Zogheib, E. H., Dupont, H., Ricome, S., Santoli, F. L., Besset, S. L., Michel, P., Gelée, B., Danin, P. -E., Goubaux, B., Crova, P. J., Phan, N. T., Berkelmans, F., Badie, J. 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L., Sagar, S. V., Palaniswamy, V., Ganesan, D., Jamaati, H., Heidari, F., Meaney, E. A., Nichol, A., Knapman, K. M., O’Croinin, D., Dunne, E. S., Breen, D. M., Clarkson, K. P., Jaafar, R. F., Dwyer, R., Amir, F., Ajetunmobi, O. O., O’Muircheartaigh, A. C., Black, C. S., Treanor, N., Collins, D. V., Altaf, W., Zani, G., Fusari, M., Spadaro, S., Volta, C. A., Graziani, R., Brunettini, B., Palmese, S., Formenti, P., Umbrello, M., Lombardo, A., Pecci, E., Botteri, M., Savioli, M., Protti, A., Mattei, A., Schiavoni, L., Tinnirello, A., Todeschini, M., Giarratano, A., Cortegiani, A., Sher, S., Rossi, A., Antonelli, M. M., Montini, L. M., Casalena, P., Scafetti, S., Panarello, G., Occhipinti, G., Patroniti, N., Pozzi, M., Biscione, R. R., Poli, M. M., Raimondi, F., Albiero, D., Crapelli, G., Beck, E., Pota, V., Schiavone, V., Molin, A., Tarantino, F., Monti, G., Frati, E., Mirabella, L., Cinnella, G., Fossali, T., Colombo, R., Pattarino, P. T. I., Mojoli, F., Braschi, A., Borotto, E. E., Cracchiolo, A. N., Palma, D. M., Raponi, F., Foti, G., Vascotto, E. R., Coppadoro, A., Brazzi, L., Floris, L., Iotti, G. A., Venti, A., Yamaguchi, O., Takagi, S., Maeyama, H. N., Watanabe, E., Yamaji, Y., Shimizu, K., Shiozaki, K., Futami, S., Ryosuke, S., Saito, K., Kameyama, Y., Ueno, K., Izawa, M., Okuda, N., Suzuki, H., Harasawa, T., Nasu, M., Takada, T., Ito, F., Nunomiya, S., Koyama, K., Abe, T., Andoh, K., Kusumoto, K., Hirata, A., Takaba, A., Kimura, H., Matsumoto, S., Higashijima, U., Honda, H., Aoki, N., Imai, H., Ogino, Y., Mizuguchi, I., Ichikado, K., Nitta, K., Mochizuki, K., Hashida, T., Tanaka, H., Nakamura, T., Niimi, D., Ueda, T., Kashiwa, Y., Uchiyama, A., Sabelnikovs, O., Oss, P., Haddad, Y., Liew, K. Y., Ñamendys-Silva, S. A., Jarquin-Badiola, Y. D., Sanchez-Hurtado, L. A., Gomez-Flores, S. S., Marin, M. C., Villagomez, A. J., Lemus, J. S., Fierro, J. M., Cervantes, M. R., Mejia, F. J. F., Dector, D., Dector, D. M., Gonzalez, D. R., Estrella, C. R., Sanchez-Medina, J. R., Ramirez-Gutierrez, A., George, F. G., Aguirre, J. S., Buensuseso, J. A., Poblano, M., Dendane, T., Balkhi, H., Elkhayari, M., Samkaoui, N., Ezzouine, H., Benslama, A., Amor, M., Maazouzi, W., Cimic, N., Beck, O., Bruns, M. M., Schouten, J. A., Rinia, M., Raaijmakers, M., Van Wezel, H. M., Heines, S. J., Strauch, U., Buise, M. P., Goodson, J. C., Browne, T. S., Navarra, L., Hunt, A., Hutchison, R. A., Bailey, M. B., Newby, L., Mcarthur, C., Kalkoff, M., Mcleod, A., Casement, J., Hacking, D. J., Andersen, F. H., Dolva, M. S., Barratt-Due, A., Noremark, K. A. L., Søreide, E., Sjøbø, B. Å., Guttormsen, A. B., Yoshido, H. H. L., Aguilar, R. Z., Oscanoa, F. A. M., Alisasis, A. U., Robles, J. B., Pasanting-Lim, R. A. B., Tan, B. C., Andruszkiewicz, P., Jakubowska, K., Coxo, C. M., Alvarez, A. M., Oliveira, B. S., Montanha, G. M., Barros, N. C., Pereira, C. S., Messias, A. M., Monteiro, J. M., Araujo, A. M., Catorze, N. T., Marum, S. M., Bouw, M. J., Gomes, R. M., Brito, V. A., Castro, S., Estilita, J. M., Barros, F. M., Serra, I. M., Martinho, A. M., Tomescu, D. R., Marcu, A., Bedreag, O. H., Papurica, M., Corneci, D. E., Negoita, S. L., Grigoriev, E., Gritsan, A. I., Gazenkampf, A. A., Almekhlafi, G., Albarrak, M. M., Mustafa, G. M., Maghrabi, K. A., Salahuddin, N., Aisa, T. M., Jabbary, A. S. A., Tabhan, E., Arabi, Y. M., Trinidad, O. A., Dorzi, H. M. A., Tabhan, E. E., Bolon, S., Smith, O., Mancebo, J., Aguirre-Bermeo, H., Lopez-Delgado, J. C., Esteve, F., Rialp, G., Forteza, C., De Haro, C., Albaiceta, G. M., De Cima-Iglesias, S., Seoane-Quiroga, L., Ceniceros-Barros, A., Ruiz-Aguilar, A. L., Claraco-Vega, L. M., Soler, J. A., del Carmen Lorente, M., Hermosa, C., Gordo, F., Prieto-González, M., López-Messa, J. B., Perez, M. P., Perez, C. P., Allue, R. M., Roche-Campo, F., Ibañez-Santacruz, M., Temprano, S., Pintado, M. C., De Pablo, R., Gómez, P. R. A., Ruiz, S. R., Moles, S. I., Jurado, M. ªT., Arizmendi, A., Piacentini, E. A., Franco, N., Honrubia, T., Cheng, M. P., Losada, E. P., Blanco, J., Yuste, L. J., Carbayo-Gorriz, C., Cazorla-Barranquero, F. G., Alonso, J. G., Alda, R. S., Algaba, Á., Navarro, G., Cereijo, E., Diaz-Rodriguez, E., Marcos, D. P., Montero, L. A., Para, L. H., Sanchez, R. J., Navalpotro, M. A. B., Abad, R. D., González, R. M., Toribio, D. P., Castro, A. G., Artiga, M. J. D., Penuelas, O., Roser, T. P., Olga, M. F., Curto, E. G., Sánchez, R. M., Imma, V. P., Elisabet, G. M., Claverias, L., Magret, M., Pellicer, A. M., Rodriguez, L. L., Sánchez-Ballesteros, J., González-Salamanca, Á., Jimenez, A. G., Huerta, F. P., Diaz, J. C. J. S., Lopez, E. B., Moya, D. D. L., Alfonso, A. A. T., Luis, P. S. E., Cesar, P. S., Rafael, S. I., Virgilio, C. G., Recio, N. N., Adamsson, R. O., Rylander, C. C., Holzgraefe, B., Broman, L. M., Wessbergh, J., Persson, L., Schiöler, F., Kedelv, H., Tibblin, A. O., Appelberg, H., Hedlund, L., Helleberg, J., Eriksson, K. E., Glietsch, R., Larsson, N., Nygren, I., Nunes, S. L., Morin, A. -K., Kander, T., Adolfsson, A., Zender, H. O., Leemann-Refondini, C., Elatrous, S., Bouchoucha, S., Chouchene, I., Ouanes, I., Souissi, A. B., Kamoun, S., Demirkiran, O., Aker, M., Erbabacan, E., Ceylan, I., Girgin, N. K., Ozcelik, M., Ünal, N., Meco, B. C., Akyol, O. O., Derman, S. S., Kennedy, B., Parhar, K., Srinivasa, L., McAuley, D., Hopkins, P., Mellis, C., Kakar, V., Hadfield, D., Vercueil, A., Bhowmick, K., Humphreys, S. K., Ferguson, A., Mckee, R., Raj, A. S., Fawkes, D. A., Watt, P., Twohey, L., Thomas, R. R. J. M., Morton, A., Kadaba, V., Smith, M. J., Hormis, A. P., Kannan, S. G., Namih, M., Reschreiter, H., Camsooksai, J., Kumar, A., Rugonfalvi, S., Nutt, C., O’Neill, O., Seasman, C., Dempsey, G., Scott, C. J., Ellis, H. E., McKechnie, S., Hutton, P. J., Di Tomasso, N. N., Vitale, M. N., Griffin, R. O., Dean, M. N., Cranshaw, J. H., Willett, E. L., Ioannou, N., Gillis, S., Csabi, P., Macfadyen, R., Dawson, H., Preez, P. D., Williams, A. J., Boyd, O., De Gordoa, L. O. -R., Bramall, J., Symmonds, S., Chau, S. K., Wenham, T., Szakmany, T., Toth-Tarsoly, P., McCalman, K. H., Alexander, P., Stephenson, L., Collyer, T., Chapman, R., Cooper, R., Allan, R. M., Sim, M., Wrathall, D. W., Irvine, D. A., Zantua, K. S., Adams, J. C., Burtenshaw, A. J., Sellors, G. P., Welters, I. D., Williams, K. E., Hessell, R. J., Oldroyd, M. G., Battle, C. E., Pillai, S., Kajtor, I., Sivashanmugavel, M., O’Kane, S. C., Donnelly, A., Frigyik, A. D., Careless, J. P., May, M. M., Stewart, R., Trinder, T. J., Hagan, S. J., Wise, M. P., Cole, J. M., MacFie, C. C., Dowling, A. T., Nuñez, E., Pittini, G., Rodriguez, R., Imperio, M. C., Santos, C., França, A. G., Ebeid, A., Deicas, A., Serra, C., Uppalapati, A., Kamel, G., Banner-Goodspeed, V. M., Beitler, J. R., Mukkera, S. R., Kulkarni, S., Lee, J., Mesar, T., Shinn, J. O., Gomaa, D., Tainter, C., Yeatts, D. J., Warren, J., Lanspa, M. J., Miller, R. R., Grissom, C. K., Brown, S. M., Bauer, P. R., Gosselin, R. J., Kitch, B. T., Cohen, J. E., Beegle, S. H., Gueret, R. 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., LUNG SAFE Investigators and the ESICM Trials Group, Madotto, F., Pham, T., Bellani, G., Bos, L.D., Simonis, F.D., Fan, E., Artigas, A., Brochard, L., Schultz, M.J., Laffey, J.G., Pesenti, A., Esteban, A., Gattinoni, L., van Haren, F., Larsson, A., McAuley, D.F., Ranieri, M., Rubenfeld, G., Thompson, B.T., Wrigge, H., Slutsky, A.S., Rios, F., Van Haren, F., Sottiaux, T., Depuydt, P., Lora, F.S., Azevedo, L.C., Bugedo, G., Qiu, H., Gonzalez, M., Silesky, J., Cerny, V., Nielsen, J., Jibaja, M., Matamis, D., Ranero, J.L., Amin, P., Hashemian, S.M., Clarkson, K., Kurahashi, K., Villagomez, A., Zeggwagh, A.A., Heunks, L.M., Laake, J.H., Palo, J.E., do Vale Fernandes, A., Sandesc, D., Arabi, Y., Bumbasierevic, V., Nin, N., Lorente, J.A., Piquilloud, L., Abroug, F., McNamee, L., Hurtado, J., Bajwa, E., Démpaire, G., Sula, H., Nunci, L., Cani, A., Zazu, A., Dellera, C., Alejandro, R.V., Daldin, J., Vinzio, M., Fernandez, R.O., Cardonnet, L.P., Bettini, L.R., Bisso, M.C., Osman, E.M., Setten, M.G., Lovazzano, P., Alvarez, J., Villar, V., Pozo, N.C., Grubissich, N., Plotnikow, G.A., Vasquez, D.N., Ilutovich, S., Tiribelli, N., Chena, A., Pellegrini, C.A., Saenz, M.G., Estenssoro, E., Brizuela, M., Gianinetto, H., Gomez, P.E., Cerrato, V.I., Bezzi, M.G., Borello, S.A., Loiacono, F.A., Fernandez, A.M., Knowles, S., Reynolds, C., Inskip, D.M., Miller, J.J., Kong, J., Whitehead, C., Bihari, S., Seven, A., Krstevski, A., Rodgers, H.J., Millar, R.T., Mckenna, T.E., Bailey, I.M., Hanlon, G.C., Aneman, A., Lynch, J.M., Azad, R., Neal, J., Woods, P.W., Roberts, B.L., Kol, M.R., Wong, H.S., Riss, K.C., Staudinger, T., Wittebole, X., Berghe, C., Bulpa, P.A., Dive, A.M., Verstraete, R., Lebbinck, H., Vermassen, J., Meersseman, P., Ceunen, H., Rosa, J.I., Beraldo, D.O., Piras, C., Rampinelli, A.M., Nassar, A.P., Jr., Mataloun, S., Moock, M., Thompson, M.M., Gonçalves, C.H., Antônio, A.C.P., Ascoli, A., Biondi, R.S., Fontenele, D.C., Nobrega, D., Sales, V.M., Shindhe, S., Ismail, D.M.A.B.P.H., Laffey, J., Beloncle, F., Davies, K.G., Cirone, R., Manoharan, V., Ismail, M., Goligher, E.C., Jassal, M., Nishikawa, E., Javeed, A., Curley, G., Rittayamai, N., Parotto, M., Ferguson, N.D., Mehta, S., Knoll, J., Pronovost, A., Canestrini, S., Bruhn, A.R., Garcia, P.H., Aliaga, F.A., Farías, P.A., Yumha, J.S., Ortiz, C.A., Salas, J.E., Saez, A.A., Vega, L.D., Labarca, E.F., Martinez, F.T., Carreño, N.G., Lora, P., Liu, H., Liu, L., Tang, R., Luo, X., An, Y., Zhao, H., Gao, Y., Zhai, Z., Ye, Z.L., Wang, W., Li, W., Li, Q., Zheng, R., Yu, W., Shen, J., Li, X., Yu, T., Lu, W., Wu, Y.Q., Huang, X.B., He, Z., Lu, Y., Han, H., Zhang, F., Sun, R., Wang, H.X., Qin, S.H., Zhu, B.H., Zhao, J., Liu, J., Li, B., Liu, J.L., Zhou, F.C., Li, Q.J., Zhang, X.Y., Li-Xin, Z., Xin-Hua, Q., Jiang, L., Gao, Y.N., Zhao, X.Y., Li, Y.Y., Li, X.L., Wang, C., Yao, Q., Yu, R., Chen, K., Shao, H., Qin, B., Huang, Q.Q., Zhu, W.H., Hang, A.Y., Hua, M.X., Li, Y., Xu, Y., Di, Y.D., Ling, L.L., Qin, T.H., Wang, S.H., Qin, J., Han, Y., Zhou, S., Vargas, M.P., Jimenez, J.I.S., Rojas, M.A.G., Solis-Quesada, J.E., Ramirez-Alfaro, C.M., Máca, 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., Roux, D., Messika, J., Kalaitzis, E., Dangers, L., Combes, A., Au, S.-M., Béduneau, G., Carpentier, D., Zogheib, E.H., Dupont, H., Ricome, S., Santoli, F.L., Besset, S.L., Michel, P., Gelée, 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., Guérin, C., Lohner, R., Kraßler, J., Schäfer, 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., Citalán, 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.A., Nichol, A., Knapman, K.M., O’Croinin, D., Dunne, E.S., Breen, D.M., Clarkson, 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Beck, O., Bruns, M.M., Schouten, J.A., Rinia, M., Raaijmakers, M., Van Wezel, H.M., Heines, S.J., Strauch, U., Buise, M.P., Goodson, J.C., Browne, T.S., Navarra, L., Hunt, A., Hutchison, R.A., Bailey, M.B., Newby, L., Mcarthur, C., Kalkoff, M., Mcleod, A., Casement, J., Hacking, D.J., Andersen, F.H., Dolva, M.S., Barratt-Due, A., Noremark, K.A.L., Søreide, E., Sjøbø, B.Å., Guttormsen, A.B., Yoshido, H.H.L., Aguilar, R.Z., Oscanoa, F.A.M., Alisasis, A.U., Robles, J.B., Pasanting-Lim, R.A.B., Tan, B.C., Andruszkiewicz, P., Jakubowska, K., Coxo, C.M., Alvarez, A.M., Oliveira, B.S., Montanha, G.M., Barros, N.C., Pereira, C.S., Messias, A.M., Monteiro, J.M., Araujo, A.M., Catorze, N.T., Marum, S.M., Bouw, M.J., Gomes, R.M., Brito, V.A., Castro, S., Estilita, J.M., Barros, F.M., Serra, I.M., Martinho, A.M., Tomescu, D.R., Marcu, A., Bedreag, O.H., Papurica, M., Corneci, D.E., Negoita, S.L., Grigoriev, E., Gritsan, A.I., Gazenkampf, A.A., Almekhlafi, G., Albarrak, M.M., Mustafa, G.M., 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Toribio, D.P., Castro, A.G., Artiga, M.J.D., Penuelas, O., Roser, T.P., Olga, M.F., Curto, E.G., Sánchez, R.M., Imma, V.P., Elisabet, G.M., Claverias, L., Magret, M., Pellicer, A.M., Rodriguez, L.L., Sánchez-Ballesteros, J., González-Salamanca, Á., Jimenez, A.G., Huerta, F.P., Diaz, J.C.J.S., Lopez, E.B., Moya, D.D.L., Alfonso, A.A.T., Luis, P.S.E., Cesar, P.S., Rafael, S.I., Virgilio, C.G., Recio, N.N., Adamsson, R.O., Rylander, C.C., Holzgraefe, B., Broman, L.M., Wessbergh, J., Persson, L., Schiöler, F., Kedelv, H., Tibblin, A.O., Appelberg, H., Hedlund, L., Helleberg, J., Eriksson, K.E., Glietsch, R., Larsson, N., Nygren, I., Nunes, S.L., Morin, A.-K., Kander, T., Adolfsson, A., Zender, H.O., Leemann-Refondini, C., Elatrous, S., Bouchoucha, S., Chouchene, I., Ouanes, I., Souissi, A.B., Kamoun, S., Demirkiran, O., Aker, M., Erbabacan, E., Ceylan, I., Girgin, N.K., Ozcelik, M., Ünal, N., Meco, B.C., Akyol, O.O., Derman, S.S., Kennedy, B., Parhar, K., Srinivasa, L., McAuley, D., Hopkins, P., Mellis, C., Kakar, V., Hadfield, D., Vercueil, A., Bhowmick, K., Humphreys, S.K., Ferguson, A., Mckee, R., Raj, A.S., Fawkes, D.A., Watt, P., Twohey, L., Thomas, R.R.J.M., Morton, A., Kadaba, V., Smith, M.J., Hormis, A.P., Kannan, S.G., Namih, M., Reschreiter, H., Camsooksai, J., Kumar, A., Rugonfalvi, S., Nutt, C., O’Neill, O., Seasman, C., Dempsey, G., Scott, C.J., Ellis, H.E., McKechnie, S., Hutton, P.J., Di Tomasso, N.N., Vitale, M.N., Griffin, R.O., Dean, M.N., Cranshaw, J.H., Willett, E.L., Ioannou, N., Gillis, S., Csabi, P., Macfadyen, R., Dawson, H., Preez, P.D., Williams, A.J., Boyd, O., De Gordoa, L.O.-R., Bramall, J., Symmonds, S., Chau, S.K., Wenham, T., Szakmany, T., Toth-Tarsoly, P., McCalman, K.H., Alexander, P., Stephenson, L., Collyer, T., Chapman, R., Cooper, R., Allan, R.M., Sim, M., Wrathall, D.W., Irvine, D.A., Zantua, K.S., Adams, J.C., Burtenshaw, A.J., Sellors, G.P., Welters, I.D., Williams, K.E., Hessell, R.J., Oldroyd, M.G., Battle, C.E., Pillai, S., Kajtor, I., Sivashanmugavel, M., O’Kane, S.C., Donnelly, A., Frigyik, A.D., Careless, J.P., May, M.M., Stewart, R., Trinder, T.J., Hagan, S.J., Wise, M.P., Cole, J.M., MacFie, C.C., Dowling, A.T., Nuñez, E., Pittini, G., Rodriguez, R., Imperio, M.C., Santos, C., França, A.G., Ebeid, A., Deicas, A., Serra, C., Uppalapati, A., Kamel, G., Banner-Goodspeed, V.M., Beitler, J.R., Mukkera, S.R., Kulkarni, S., Lee, J., Mesar, T., Shinn, J.O., Gomaa, D., Tainter, C., Yeatts, D.J., Warren, J., Lanspa, M.J., Miller, R.R., Grissom, C.K., Brown, S.M., Bauer, P.R., Gosselin, R.J., Kitch, B.T., Cohen, J.E., Beegle, S.H., Gueret, R.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., LUNG SAFE Investigators and the ESICM Trials Group, Madotto, F, Pham, T, Bellani, G, Bos, L, Simonis, F, Fan, E, Artigas, A, Brochard, L, Schultz, M, Laffey, J, Pesenti, A, Esteban, A, Gattinoni, L, van Haren, F, 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, Piquilloud, L, Abroug, F, Mcnamee, L, Hurtado, J, Bajwa, E, Démpaire, G, Sula, H, Nunci, L, Cani, A, Zazu, A, Dellera, C, Alejandro, R, Daldin, J, Vinzio, M, Fernandez, R, Cardonnet, L, Bettini, L, Bisso, M, Osman, E, Setten, M, Lovazzano, P, Alvarez, J, Villar, V, Pozo, N, Grubissich, N, Plotnikow, G, Vasquez, D, Ilutovich, S, Tiribelli, N, Chena, A, Pellegrini, C, Saenz, M, Estenssoro, E, Brizuela, M, Gianinetto, H, Gomez, P, Cerrato, V, Bezzi, M, Borello, S, Loiacono, F, Fernandez, A, Knowles, S, Reynolds, C, Inskip, D, Miller, J, Kong, J, Whitehead, C, Bihari, S, Seven, A, Krstevski, A, Rodgers, H, Millar, R, Mckenna, T, Bailey, I, Hanlon, G, Aneman, A, Lynch, J, Azad, R, Neal, J, Woods, P, Roberts, B, Kol, M, Wong, H, Riss, K, Staudinger, T, Wittebole, X, Berghe, C, Bulpa, P, Dive, A, Verstraete, R, Lebbinck, H, Vermassen, J, Meersseman, P, Ceunen, H, Rosa, J, Beraldo, D, Piras, C, Rampinelli, A, Nassar, A, Mataloun, S, Moock, M, Thompson, M, Gonçalves, C, Antônio, A, Ascoli, A, Biondi, R, Fontenele, D, Nobrega, D, Sales, V, Shindhe, S, Ismail, D, Beloncle, F, Davies, K, Cirone, R, Manoharan, V, Ismail, M, Goligher, E, Jassal, M, Nishikawa, E, Javeed, A, Curley, G, Rittayamai, N, Parotto, M, Ferguson, N, Mehta, S, Knoll, J, Pronovost, A, Canestrini, S, Bruhn, A, Garcia, P, Aliaga, F, Farías, P, Yumha, J, Ortiz, C, Salas, J, Saez, A, Vega, L, Labarca, E, Martinez, F, Carreño, N, Lora, P, Liu, H, Liu, L, Tang, R, Luo, X, An, Y, Zhao, H, Gao, Y, Zhai, Z, Ye, Z, Wang, W, Li, W, Li, Q, Zheng, R, Yu, W, Shen, J, Li, X, Yu, T, Lu, W, Wu, Y, Huang, X, He, Z, Lu, Y, Han, H, Zhang, F, Sun, R, Wang, H, Qin, S, Zhu, B, Zhao, J, Liu, J, Li, B, Zhou, F, Zhang, X, Li-Xin, Z, Xin-Hua, Q, Jiang, L, Zhao, X, Li, Y, Wang, C, Yao, Q, Yu, R, Chen, K, Shao, H, Qin, B, Huang, Q, Zhu, W, Hang, A, Hua, M, Xu, Y, Di, Y, Ling, L, Qin, T, Wang, S, Qin, J, Han, Y, Zhou, S, Vargas, M, Jimenez, J, Rojas, M, Solis-Quesada, J, Ramirez-Alfaro, C, Máca, J, Sklienka, P, Gjedsted, J, Christiansen, A, Villamagua, B, 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, Daviaud, F, Fartoukh, M, Barberet, G, Biehler, J, Dellamonica, J, Doyen, D, Arnal, J, Briquet, A, Hraiech, S, Papazian, L, Roux, D, Messika, J, Kalaitzis, E, Dangers, L, Combes, A, Au, S, Béduneau, G, Carpentier, D, Zogheib, E, Dupont, H, Ricome, S, Santoli, F, Besset, S, Michel, P, Gelée, B, Danin, P, Goubaux, B, Crova, P, Phan, N, Berkelmans, F, Badie, J, Tapponnier, R, Gally, J, Khebbeb, S, Herbrecht, J, Schneider, F, Declercq, P, Rigaud, J, Duranteau, J, Harrois, A, Chabanne, R, Marin, J, Bigot, C, Thibault, S, Ghazi, M, Boukhazna, M, Zein, S, Richecoeur, J, Combaux, D, Grelon, F, Le Moal, C, Sauvadet, E, Robine, A, Lemiale, V, Reuter, D, Dres, M, Demoule, A, Goldgran-Toledano, D, Baboi, L, Guérin, C, Lohner, R, Kraßler, J, Schäfer, S, Zacharowski, K, Meybohm, P, Reske, A, Simon, P, Hopf, H, Schuetz, M, Baltus, T, Papanikolaou, M, Papavasilopoulou, T, Zacharas, G, Ourailogloy, V, Mouloudi, E, Massa, E, Nagy, E, Stamou, E, Kiourtzieva, E, Oikonomou, M, Avila, L, Cortez, C, Citalán, J, Jog, S, Sable, S, Shah, B, Gurjar, M, Baronia, A, Memon, M, Muthuchellappan, R, Ramesh, V, Shenoy, A, Unnikrishnan, R, Dixit, S, Rhayakar, R, Ramakrishnan, N, Bhardwaj, V, Mahto, H, Sagar, S, Palaniswamy, V, Ganesan, D, Jamaati, H, Heidari, F, Meaney, E, Nichol, A, Knapman, K, O’Croinin, D, Dunne, E, Breen, D, Jaafar, R, Dwyer, R, Amir, F, Ajetunmobi, O, O’Muircheartaigh, A, Black, C, Treanor, N, Collins, D, Altaf, W, Zani, G, Fusari, M, Spadaro, S, Volta, C, Graziani, R, Brunettini, B, Palmese, S, Formenti, P, Umbrello, M, Lombardo, A, Pecci, E, Botteri, M, Savioli, M, Protti, A, Mattei, A, Schiavoni, L, Tinnirello, A, Todeschini, M, Giarratano, A, Cortegiani, A, Sher, S, Rossi, A, Antonelli, M, Montini, L, Casalena, P, Scafetti, S, Panarello, G, Occhipinti, G, Patroniti, N, Pozzi, M, Biscione, R, Poli, M, Raimondi, F, Albiero, D, Crapelli, G, Beck, E, Pota, V, Schiavone, V, Molin, A, Tarantino, F, Monti, G, Frati, E, Mirabella, L, Cinnella, G, Fossali, T, Colombo, R, Pattarino, P, Mojoli, F, Braschi, A, Borotto, E, Cracchiolo, A, Palma, D, Raponi, F, Foti, G, Vascotto, E, Coppadoro, A, Brazzi, L, Floris, L, Iotti, G, Venti, A, Yamaguchi, O, Takagi, S, Maeyama, H, Watanabe, E, Yamaji, Y, Shimizu, K, Shiozaki, K, Futami, S, Ryosuke, S, Saito, K, Kameyama, Y, Ueno, K, Izawa, M, Okuda, N, Suzuki, H, Harasawa, T, Nasu, M, Takada, T, Ito, F, Nunomiya, S, Koyama, K, Abe, T, Andoh, K, Kusumoto, K, Hirata, A, Takaba, A, Kimura, H, Matsumoto, S, Higashijima, U, Honda, H, Aoki, N, Imai, H, Ogino, Y, Mizuguchi, I, Ichikado, K, Nitta, K, Mochizuki, K, Hashida, T, Tanaka, H, Nakamura, T, Niimi, D, Ueda, T, Kashiwa, Y, Uchiyama, A, Sabelnikovs, O, Oss, P, Haddad, Y, Liew, K, Ñamendys-Silva, S, Jarquin-Badiola, Y, Sanchez-Hurtado, L, Gomez-Flores, S, Marin, M, Lemus, J, Fierro, J, Cervantes, M, Mejia, F, Dector, D, Gonzalez, D, Estrella, C, Sanchez-Medina, J, Ramirez-Gutierrez, A, George, F, Aguirre, J, Buensuseso, J, Poblano, M, Dendane, T, Balkhi, H, Elkhayari, M, Samkaoui, N, Ezzouine, H, Benslama, A, Amor, M, Maazouzi, W, Cimic, N, Beck, O, Bruns, M, Schouten, J, Rinia, M, Raaijmakers, M, van Wezel, H, Heines, S, Strauch, U, Buise, M, Goodson, J, Browne, T, Navarra, L, Hunt, A, Hutchison, R, Bailey, M, Newby, L, Mcarthur, C, Kalkoff, M, Mcleod, A, Casement, J, Hacking, D, Andersen, F, Dolva, M, Barratt-Due, A, Noremark, K, Søreide, E, Sjøbø, B, Guttormsen, A, Yoshido, H, Aguilar, R, Oscanoa, F, Alisasis, A, Robles, J, Pasanting-Lim, R, Tan, B, Andruszkiewicz, P, Jakubowska, K, Coxo, C, Alvarez, A, Oliveira, B, Montanha, G, Barros, N, Pereira, C, Messias, A, Monteiro, J, Araujo, A, Catorze, N, Marum, S, Bouw, M, Gomes, R, Brito, V, Castro, S, Estilita, J, Barros, F, Serra, I, Martinho, A, Tomescu, D, Marcu, A, Bedreag, O, Papurica, M, Corneci, D, Negoita, S, Grigoriev, E, Gritsan, A, Gazenkampf, A, Almekhlafi, G, Albarrak, M, Mustafa, G, Maghrabi, K, Salahuddin, N, Aisa, T, Jabbary, A, Tabhan, E, Trinidad, O, Dorzi, H, Bolon, S, Smith, O, Mancebo, J, Aguirre-Bermeo, H, Lopez-Delgado, J, Esteve, F, Rialp, G, Forteza, C, de Haro, C, Albaiceta, G, de Cima-Iglesias, S, Seoane-Quiroga, L, Ceniceros-Barros, A, Ruiz-Aguilar, A, Claraco-Vega, L, Soler, J, Del Carmen Lorente, M, Hermosa, C, Gordo, F, Prieto-González, M, López-Messa, J, Perez, M, Perez, C, Allue, R, Roche-Campo, F, Ibañez-Santacruz, M, Temprano, S, Pintado, M, de Pablo, R, Gómez, P, Ruiz, S, Moles, S, Jurado, M, Arizmendi, A, Piacentini, E, Franco, N, Honrubia, T, Cheng, M, Losada, E, Blanco, J, Yuste, L, Carbayo-Gorriz, C, Cazorla-Barranquero, F, Alonso, J, Alda, R, Algaba, Á, Navarro, G, Cereijo, E, Diaz-Rodriguez, E, Marcos, D, Montero, L, Para, L, Sanchez, R, Navalpotro, M, Abad, R, González, R, Toribio, D, Castro, A, Artiga, M, Penuelas, O, Roser, T, Olga, M, Curto, E, Sánchez, R, Imma, V, Elisabet, G, Claverias, L, Magret, M, Pellicer, A, Rodriguez, L, Sánchez-Ballesteros, J, González-Salamanca, Á, Jimenez, A, Huerta, F, Diaz, J, Lopez, E, Moya, D, Alfonso, A, Luis, P, Cesar, P, Rafael, S, Virgilio, C, Recio, N, Adamsson, R, Rylander, C, Holzgraefe, B, Broman, L, Wessbergh, J, Persson, L, Schiöler, F, Kedelv, H, Tibblin, A, Appelberg, H, Hedlund, L, Helleberg, J, Eriksson, K, Glietsch, R, Larsson, N, Nygren, I, Nunes, S, Morin, A, Kander, T, Adolfsson, A, Zender, H, Leemann-Refondini, C, Elatrous, S, Bouchoucha, S, Chouchene, I, Ouanes, I, Souissi, A, Kamoun, S, Demirkiran, O, Aker, M, Erbabacan, E, Ceylan, I, Girgin, N, Ozcelik, M, Ünal, N, Meco, B, Akyol, O, Derman, S, Kennedy, B, Parhar, K, Srinivasa, L, Hopkins, P, Mellis, C, Kakar, V, Hadfield, D, Vercueil, A, Bhowmick, K, Humphreys, S, Ferguson, A, Mckee, R, Raj, A, Fawkes, D, Watt, P, Twohey, L, Thomas, R, Morton, A, Kadaba, V, Smith, M, Hormis, A, Kannan, S, Namih, M, Reschreiter, H, Camsooksai, J, Kumar, A, Rugonfalvi, S, Nutt, C, O’Neill, O, Seasman, C, Dempsey, G, Scott, C, Ellis, H, Mckechnie, S, Hutton, P, Di Tomasso, N, Vitale, M, Griffin, R, Dean, M, Cranshaw, J, Willett, E, Ioannou, N, Gillis, S, Csabi, P, Macfadyen, R, Dawson, H, Preez, P, Williams, A, Boyd, O, de Gordoa, L, Bramall, J, Symmonds, S, Chau, S, Wenham, T, Szakmany, T, Toth-Tarsoly, P, Mccalman, K, Alexander, P, Stephenson, L, Collyer, T, Chapman, R, Cooper, R, Allan, R, Sim, M, Wrathall, D, Irvine, D, Zantua, K, Adams, J, Burtenshaw, A, Sellors, G, Welters, I, Williams, K, Hessell, R, Oldroyd, M, Battle, C, Pillai, S, Kajtor, I, Sivashanmugavel, M, O’Kane, S, Donnelly, A, Frigyik, A, Careless, J, May, M, Stewart, R, Trinder, T, Hagan, S, Wise, M, Cole, J, Macfie, C, Dowling, A, Nuñez, E, Pittini, G, Rodriguez, R, Imperio, M, Santos, C, França, A, Ebeid, A, Deicas, A, Serra, C, Uppalapati, A, Kamel, G, Banner-Goodspeed, V, Beitler, J, Mukkera, S, Kulkarni, S, Lee, J, Mesar, T, Shinn, J, Gomaa, D, Tainter, C, Yeatts, D, Warren, J, Lanspa, M, Miller, R, Grissom, C, Brown, S, Bauer, P, Gosselin, R, Kitch, B, Cohen, J, Beegle, S, Gueret, R, Tulaimat, A, Choudry, S, Stigler, W, Batra, H, Huff, N, Lamb, K, Oetting, T, Mohr, N, Judy, C, Saito, S, Kheir, F, Schlichting, A, Delsing, A, Crouch, D, Elmasri, M, Dreyer, K, Blakeman, T, Baron, R, Grijalba, C, Hou, P, Seethala, R, Aisiku, I, Henderson, G, Frendl, G, Hou, S, Owens, R, Schomer, A, Bumbasirevic, V, Jovanovic, B, Surbatovic, M, Veljovic, M, Madotto, Fabiana, Pham, Tài, Bellani, Giacomo, Bos, Lieuwe D., Simonis, Fabienne D., Fan, Eddy, Artigas, Antonio, Brochard, Laurent, Schultz, Marcus J., Laffey, John G., Pesenti, Antonio, Esteban, Andre, Gattinoni, Luciano, van Haren, Frank, Larsson, Ander, McAuley, Daniel F., Ranieri, Marco, Rubenfeld, Gordon, Thompson, B. Taylor, Wrigge, Hermann, Slutsky, Arthur S., Rios, Fernando, Lora, Fredy S., Azevedo, Luciano Cesar, Bugedo, Guillermo, Qiu, Haibo, Gonzalez, Marco, Silesky, Juan, Cerny, Vladimir, Nielsen, Jona, Jibaja, Manuel, Matamis, Dimitrio, Ranero, Jorge Lui, Amin, Pravin, Clarkson, Kevin, Kurahashi, Kiyoyasu, Villagomez, Asisclo, Zeggwagh, Amine Ali, Heunks, Leo M., Laake, Jon Henrik, Palo, Jose Emmanuel, Do Vale Fernandes, Antero, Sandesc, Dorel, Arabi, Yaasen, Bumbasierevic, Vesna, Nin, Nicola, Lorente, Jose A., Piquilloud, Lise, Abroug, Fekri, McNamee, Lia, Hurtado, Javier, Bajwa, Ed, Démpaire, Gabriel, Sula, Hektor, Nunci, Lordian, Cani, Alma, Zazu, Alan, Dellera, Christian, Alejandro, Risso V., Daldin, Julio, Vinzio, Mauricio, Fernandez, Ruben O., Cardonnet, Luis P., Bettini, Lisandro R., Bisso, Mariano Carboni, Osman, Emilio M., Setten, Mariano G., Lovazzano, Pablo, Alvarez, Javier, Villar, Veronica, Pozo, Norberto C., Grubissich, Nicola, Plotnikow, Gustavo A., Vasquez, Daniela N., Ilutovich, Santiago, Tiribelli, Norberto, Chena, Ariel, Pellegrini, Carlos A., Saenz, María G., Estenssoro, Elisa, Brizuela, Matia, Gianinetto, Hernan, Gomez, Pablo E., Cerrato, Valeria I., Bezzi, Marco G., Borello, Silvina A., Loiacono, Flavia A., Fernandez, Adriana M., Knowles, Serena, Reynolds, Claire, Inskip, Deborah M., Miller, Jennene J., Kong, Jing, Whitehead, Christina, Bihari, Shailesh, Seven, Aylin, Krstevski, Amanda, Rodgers, Helen J., Millar, Rebecca T., Mckenna, Toni E., Bailey, Irene M., Hanlon, Gabrielle C., Aneman, Ander, Lynch, Joan M., Azad, Raman, Neal, John, Woods, Paul W., Roberts, Brigit L., Kol, Mark R., Wong, Helen S., Riss, Katharina C., Staudinger, Thoma, Wittebole, Xavier, Berghe, Caroline, Bulpa, Pierre A., Dive, Alain M., Verstraete, Rik, Lebbinck, Herve, Depuydt, Pieter, Vermassen, Jori, Meersseman, Philippe, Ceunen, Helga, Rosa, Jonas I., Beraldo, Daniel O., Piras, Claudio, Rampinelli, Adenilton M., Nassar, Antonio P., Mataloun, Sergio, Moock, Marcelo, Thompson, Marlus M., Gonçalves, Claudio H., Antônio, Ana Carolina P., Ascoli, Aline, Biondi, Rodrigo S., Fontenele, Danielle C., Nobrega, Danielle, Sales, Vanessa M., Shindhe, Suresh, Ismail, Dk Maizatul Aiman B. Pg Hj, Laffey, John, Beloncle, Francoi, Davies, Kyle G., Cirone, Rob, Manoharan, Venika, Ismail, Mehvish, Goligher, Ewan C., Jassal, Mandeep, Nishikawa, Erin, Javeed, Areej, Curley, Gerard, Rittayamai, Nuttapol, Parotto, Matteo, Ferguson, Niall D., Mehta, Sangeeta, Knoll, Jenny, Pronovost, Antoine, Canestrini, Sergio, Bruhn, Alejandro R., Garcia, Patricio H., Aliaga, Felipe A., Farías, Pamela A., Yumha, Jacob S., Ortiz, Claudia A., Salas, Javier E., Saez, Alejandro A., Vega, Luis D., Labarca, Eduardo F., Martinez, Felipe T., Carreño, Nicolás G., Lora, Pilar, Liu, Haitao, Liu, Ling, Tang, Rui, Luo, Xiaoming, An, Youzhong, Zhao, Huiying, Gao, Yan, Zhai, Zhe, Ye, Zheng L., Wang, Wei, Li, Wenwen, Li, Qingdong, Zheng, Ruiqiang, Yu, Wenkui, Shen, Juanhong, Li, Xinyu, Yu, Tao, Lu, Weihua, Wu, Ya, Huang, Xiao B., He, Zhenyang, Lu, Yuanhua, Han, Hui, Zhang, Fan, Sun, Renhua, Wang, Hua X., Qin, Shu H., Zhu, Bao H., Zhao, Jun, Liu, Jian, Li, Bin, Liu, Jing L., Zhou, Fa, Li, Qiong J., Zhang, Xing Y., Li-Xin, Zhou, Xin-Hua, Qiang, Jiang, Liangyan, Gao, Yuan N., Zhao, Xian Y., Li, Yuan Y., Li, Xiao L., Wang, Chunting, Yao, Qingchun, Yu, Rongguo, Chen, Kai, Shao, Huanzhang, Qin, Bingyu, Huang, Qing Q., Zhu, Wei H., Hang, Ai, Hua, Ma, Li, Yimin, Xu, Yonghao, Di, Yu, Ling, Long L., Qin, Tie H., Wang, Shou H., Qin, Junping, Han, Yi, Zhou, Suming, Vargas, Monica P., Jimenez, Juan I. Silesky, Rojas, Manuel A. González, Solis-Quesada, Jaime E., Ramirez-Alfaro, Christian M., Máca, Jan, Sklienka, Peter, Gjedsted, Jakob, Christiansen, Aage, Villamagua, Boris G., Llano, Miguel, Burtin, Philippe, Buzancais, Gautier, Beuret, Pascal, Pelletier, Nicola, Mortaza, Satar, Mercat, Alain, Chelly, Jonathan, Jochmans, Sébastien, Terzi, Nicola, Daubin, Cédric, Carteaux, Guillaume, de Prost, Nicola, Chiche, Jean-Daniel, Daviaud, Fabrice, Pham, Tai, Fartoukh, Muriel, Barberet, Guillaume, Biehler, Jerome, Dellamonica, Jean, Doyen, Deni, Arnal, Jean-Michel, Briquet, Anai, Hraiech, Sami, Papazian, Laurent, Roux, Damien, Messika, Jonathan, Kalaitzis, Evangelo, Dangers, Laurence, Combes, Alain, Au, Siu-Ming, Béduneau, Gaetan, Carpentier, Dorothée, Zogheib, Elie H., Dupont, Herve, Ricome, Sylvie, Santoli, Francesco L., Besset, Sebastien L., Michel, Philippe, Gelée, Bruno, Danin, Pierre-Eric, Goubaux, Bernard, Crova, Philippe J., Phan, Nga T., Berkelmans, Frantz, Badie, Julio C., Tapponnier, Romain, Gally, Josette, 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Tallet, Luis, Palazon Sanchez Eugenio, Cesar, Palazon Sanchez, Rafael, Sánchez I., Virgilio, Corcoles G., Recio, Noelia N., Adamsson, Richard O., Rylander, Christian C., Holzgraefe, Bernhard, Broman, Lars M., Wessbergh, Joanna, Persson, Linnea, Schiöler, Fredrik, Kedelv, Han, Tibblin, Anna Oscarsson, Appelberg, Henrik, Hedlund, Lar, Helleberg, Johan, Eriksson, Karin E., Glietsch, Rita, Larsson, Nikla, Nygren, Ingela, Nunes, Silvia L., Morin, Anna-Karin, Kander, Thoma, Adolfsson, Anne, Zender, Hervé O., Leemann-Refondini, Corinne, Elatrous, Souheil, Bouchoucha, Slaheddine, Chouchene, Imed, Ouanes, Islem, Souissi, Asma Ben, Kamoun, Salma, Demirkiran, Oktay, Aker, Mustafa, Erbabacan, Emre, Ceylan, Ilkay, Girgin, Nermin Kelebek, Ozcelik, Menekse, Ünal, Necmettin, Meco, Basak Ceyda, Akyol, Onat O., Derman, Suleyman S., Kennedy, Barry, Parhar, Ken, Srinivasa, Latha, McAuley, Danny, Hopkins, Phil, Mellis, Clare, Kakar, Vivek, Hadfield, Dan, Vercueil, Andre, Bhowmick, Kaushik, Humphreys, Sally K., Ferguson, Andrew, Mckee, Raymond, Raj, Ashok S., Fawkes, Danielle A., Watt, Philip, Twohey, Linda, Thomas, Rajeev R. 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John, Hagan, Samantha J., Wise, Matt P., Cole, Jade M., MacFie, Caroline C., Dowling, Anna T., Nin, Nicolá, Nuñez, Edgardo, Pittini, Gustavo, Rodriguez, Ruben, Imperio, María C., Santos, Cristina, França, Ana G., Ebeid, Alejandro, Deicas, Alberto, Serra, Carolina, Uppalapati, Aditya, Kamel, Ghassan, Banner-Goodspeed, Valerie M., Beitler, Jeremy R., Mukkera, Satyanarayana Reddy, Kulkarni, Shreedhar, Lee, Jarone, Mesar, Tomaz, Shinn, John O., Gomaa, Dina, Tainter, Christopher, Yeatts, Dale J., Warren, Jessica, Lanspa, Michael J., Miller, Russel R., Grissom, Colin K., Brown, Samuel M., Bauer, Philippe R., Gosselin, Ryan J., Kitch, Barrett T., Cohen, Jason E., Beegle, Scott H., Gueret, Renaud M., Tulaimat, Aiman, Choudry, Shazia, Stigler, William, Batra, Hitesh, Huff, Nidhi G., Lamb, Keith D., Oetting, Trevor W., Mohr, Nicholas M., Judy, Claine, Saito, Shigeki, Kheir, Fayez M., Kheir, Fayez, Schlichting, Adam B., Delsing, Angela, Crouch, Daniel R., Elmasri, Mary, Ismail, Dina, Dreyer, Kyle R., Blakeman, Thomas C., Baron, Rebecca M., Grijalba, Carolina Quintana, Hou, Peter C., Seethala, Raghu, Aisiku, Imo, Henderson, Galen, Frendl, Gyorgy, Hou, Sen-Kuang, Owens, Robert L., Schomer, Ashley, Bumbasirevic, Vesna, Jovanovic, Bojan, Surbatovic, Maja, Veljovic, Milic, Intensive Care Medicine, Graduate School, ACS - Heart failure & arrhythmias, AII - Inflammatory diseases, ACS - Diabetes & metabolism, ACS - Pulmonary hypertension & thrombosis, ACS - Microcirculation, Bos, L. D., Simonis, F. D., Schultz, M. J., Laffey, J. G., Mcauley, D. F., Thompson, B. T., Slutsky, A. S., Lora, F. S., Azevedo, L. C., Ranero, J. L., Hashemian, S. M., Zeggwagh, A. A., Heunks, L. M., Laake, J. H., Palo, J. E., Lorente, J. A., Mcnamee, L., Dempaire, G., Alejandro, R. V., Fernandez, R. O., Cardonnet, L. P., Bettini, L. R., Bisso, M. C., Osman, E. M., Setten, M. G., Pozo, N. C., Plotnikow, G. A., Vasquez, D. N., Pellegrini, C. A., Saenz, M. G., Gomez, P. E., Cerrato, V. I., Bezzi, M. G., Borello, S. A., Loiacono, F. A., Fernandez, A. M., Inskip, D. M., Miller, J. J., Rodgers, H. J., Millar, R. T., Mckenna, T. E., Bailey, I. M., Hanlon, G. C., Lynch, J. M., Woods, P. W., Roberts, B. L., Kol, M. R., Wong, H. S., Riss, K. C., Bulpa, P. A., Dive, A. M., Rosa, J. I., Beraldo, D. O., Rampinelli, A. M., Nassar, A. P., Thompson, M. M., Goncalves, C. H., Antonio, A. C. P., Biondi, R. S., Fontenele, D. C., Sales, V. M., Ismail, D. M. A. B. P. H., Davies, K. G., Goligher, E. C., Ferguson, N. D., Bruhn, A. R., Garcia, P. H., Aliaga, F. A., Farias, P. A., Yumha, J. S., Ortiz, C. A., Salas, J. E., Saez, A. A., Vega, L. D., Labarca, E. F., Martinez, F. T., Carreno, N. G., Ye, Z. L., Wu, Y. Q., Huang, X. B., Wang, H. X., Qin, S. H., Zhu, B. H., Liu, J. L., Zhou, F. C., Li, Q. J., Zhang, X. Y., Gao, Y. N., Zhao, X. Y., Li, Y. Y., Li, X. L., Huang, Q. Q., Zhu, W. H., Hang, A. Y., Hua, M. X., Di, Y. D., Ling, L. L., Qin, T. H., Wang, S. H., Vargas, M. P., Jimenez, J. I. S., Rojas, M. A. G., Solis-Quesada, J. E., Ramirez-Alfaro, C. M., Maca, J., Villamagua, B. G., Chiche, J. -D., Arnal, J. -M., Au, S. -M., Beduneau, G., Zogheib, E. H., Santoli, F. L., Besset, S. L., Gelee, B., Danin, P. -E., Crova, P. J., Phan, N. T., Badie, J. C., Herbrecht, J. -E., Declercq, P. -L. M., Rigaud, J. -P., Zein, S. O., Richecoeur, J. R., Combaux, D. M., Lemoal, C., Sauvadet, E. P., Guerin, C., Krassler, J., Schafer, S., Zacharowski, K. D., Reske, A. W., Hopf, H. -B. F., Papanikolaou, M. N., Papavasilopoulou, T. G., Zacharas, G. A., 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., Baronia, A. K., Ramesh, V. J., Dixit, S. B., Rhayakar, R. V., Bhardwaj, V. K., Mahto, H. L., Sagar, S. V., Meaney, E. A., Knapman, K. M., O'Croinin, D., Dunne, E. S., Breen, D. M., Clarkson, K. P., Jaafar, R. F., Ajetunmobi, O. O., O'Muircheartaigh, A. C., Black, C. S., Collins, D. V., Volta, C. A., Antonelli, M. M., Montini, L. M., Biscione, R. R., Poli, M. M., Pattarino, P. T. I., Borotto, E. E., Cracchiolo, A. N., Palma, D. M., Vascotto, E. R., Iotti, G. A., Maeyama, H. N., Liew, K. Y., Namendys-Silva, S. A., Jarquin-Badiola, Y. D., Sanchez-Hurtado, L. A., Gomez-Flores, S. S., Marin, M. C., Villagomez, A. J., Lemus, J. S., Fierro, J. M., Cervantes, M. R., Mejia, F. J. F., Dector, D. M., Gonzalez, D. R., Estrella, C. R., Sanchez-Medina, J. 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M., Ruiz-Aguilar, A. L., Claraco-Vega, L. M., Soler, J. A., Prieto-Gonzalez, M., Lopez-Messa, J. B., Perez, M. P., Perez, C. P., Allue, R. M., Ibanez-Santacruz, M., Pintado, M. C., Depablo, R., Gomez, P. R. A., Ruiz, S. R., Moles, S. I., Jurado, M. T., Piacentini, E. A., Cheng, M. P., Losada, E. P., Yuste, L. J., Cazorla-Barranquero, F. G., Alonso, J. G., Alda, R. S., Algaba, A., Marcos, D. P., Montero, L. A., Para, L. H., Sanchez, R. J., Navalpotro, M. A. B., Abad, R. D., Gonzalez, R. M., Toribio, D. P., Castro, A. G., Artiga, M. J. D., Roser, T. P., Olga, M. F., Curto, E. G., Sanchez, R. M., Imma, V. P., Elisabet, G. M., Pellicer, A. M., Rodriguez, L. L., Sanchez-Ballesteros, J., Gonzalez-Salamanca, A., Jimenez, A. G., Huerta, F. P., Diaz, J. C. J. S., Lopez, E. B., Moya, D. D. L., Alfonso, A. A. T., Luis, P. S. E., Cesar, P. S., Rafael, S. I., Virgilio, C. G., Recio, N. N., Adamsson, R. O., Rylander, C. C., Broman, L. M., Schioler, F., Tibblin, A. O., Eriksson, K. E., Nunes, S. 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K., Brown, S. M., Bauer, P. R., Gosselin, R. J., Kitch, B. T., Cohen, J. E., Beegle, S. H., Gueret, R. M., Huff, N. G., Lamb, K. D., Oetting, T. W., Mohr, N. M., Kheir, F. M., Schlichting, A. B., Crouch, D. R., Dreyer, K. R., Blakeman, T. C., Baron, R. M., Grijalba, C. Q., Hou, P. C., Hou, S. -K., and Owens, R. L.
Subjects: Male, ARDS, medicine.medical_treatment, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], ARDS reassessment, ARDS Survival, Berlin criteria ARDS, Persisting ARDS, Critical Care and Intensive Care Medicine, assisted ventilation, 0302 clinical medicine, Risk Factors, 030212 general & internal medicine, risk factor, Adult, Tidal volume, comparative study, education.field_of_study, Respiratory Distress Syndrome, Mortality rate, Remission Induction, tidal volume, artificial ventilation, clinical trial, immunosuppressive treatment, adult respiratory distress syndrome, Middle Aged, Monte Carlo method, medicine.anatomical_structure, classification, positive end expiratory pressure, Cardiology, Disease Progression, SOFA score, disease severity, Female, Adult, medicine.medical_specialty, Population, disease classification, Article, NO, 03 medical and health sciences, remission, length of stay, Anesthesiology, Internal medicine, medicine, pneumonia, Sequential Organ Failure Assessment Score, Humans, human, education, Aged, Mechanical ventilation, hospital mortality, Lung, business.industry, Risk Factor, disease association, Respiratory Distress Syndrome, Adult, medicine.disease, major clinical study, mortality, Respiration, Artificial, breathing rate, 030228 respiratory system, disease exacerbation, business
Abstract: Purpose: To evaluate patients with resolved versus confirmed ARDS, identify subgroups with substantial mortality risk, and to determine the utility of day 2 ARDS reclassification. Methods: Our primary objective, in this secondary LUNG SAFE analysis, was to compare outcome in patients with resolved versus confirmed ARDS after 24 h. Secondary objectives included identifying factors associated with ARDS persistence and mortality, and the utility of day 2 ARDS reclassification. Results: Of 2377 patients fulfilling the ARDS definition on the first day of ARDS (day 1) and receiving invasive mechanical ventilation, 503 (24%) no longer fulfilled the ARDS definition the next day, 52% of whom initially had moderate or severe ARDS. Higher tidal volume on day 1 of ARDS was associated with confirmed ARDS [OR 1.07 (CI 1.01–1.13), P = 0.035]. Hospital mortality was 38% overall, ranging from 31% in resolved ARDS to 41% in confirmed ARDS, and 57% in confirmed severe ARDS at day 2. In both resolved and confirmed ARDS, age, non-respiratory SOFA score, lower PEEP and P/F ratio, higher peak pressure and respiratory rate were each associated with mortality. In confirmed ARDS, pH and the presence of immunosuppression or neoplasm were also associated with mortality. The increase in area under the receiver operating curve for ARDS reclassification on day 2 was marginal. Conclusions: ARDS, whether resolved or confirmed at day 2, has a high mortality rate. ARDS reclassification at day 2 has limited predictive value for mortality. The substantial mortality risk in severe confirmed ARDS suggests that complex interventions might best be tested in this population. Trial Registration: ClinicalTrials.gov NCT02010073. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature and ESICM.
Published: 2018

17. Epithelial-myoepithelial Carcinoma of the Base of Tongue

Author: Cristina Isabel Sanz Sánchez, Lidia Pérez Villa, and Óscar Emilio Cazorla Ramos
Subjects: Pathology, medicine.medical_specialty, medicine.anatomical_structure, business.industry, Tongue, Medicine, General Medicine, business, medicine.disease, Base (exponentiation), Epithelial-myoepithelial carcinoma
Published: 2021

18. Circulating miR-1246 in the Progression of Chronic Obstructive Pulmonary Disease (COPD) in Patients from the BODE Cohort

Author: Ciro Casanova, Elizabeth Córdoba-Lanús, Glorian Mura-Escorche, Sara Cazorla-Rivero, Francisca Gonzalvo-Hernández, and Delia Mayato
Subjects: Oncology, COPD, medicine.medical_specialty, business.industry, Pulmonary disease, General Medicine, respiratory system, medicine.disease, Serum samples, Pathophysiology, respiratory tract diseases, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, DLCO, Internal medicine, Cohort, Medicine, Biomarker (medicine), In patient, 030212 general & internal medicine, business
Abstract: Background COPD is characterized by a persistent inflammatory response, especially against cigarette smoke. COPD patients may develop varying degrees of emphysematous destruction of the lungs. A pathophysiological role for miRNAs in COPD has been suggested in several studies. We examined changes in microRNAs expression profile during 10 years follow-up in relation to COPD progression. Methods Clinical and lung function parameters were registered from every subject included in the study. miRNAs expression was determined in 14 serum samples from 7 patients in two moments (4 smokers with COPD (BODE cohort) and 3 smokers without COPD) by next generation sequencing (NGS) at baseline and after 10 years follow-up. A validation study was performed by qPCR in 20 patients with COPD (13 emphysema-diagnosed by CTscan) and 10 smoker controls at baseline and after 10 years follow-up. hsa-miRNA-20a-5p and hsa-let-7d-5p were used as endogenous controls. Results A total of 198 miRNAs (≥10TPM) were identified by NGS. Between these, hsa-miR-1246 was found significantly downregulated in COPD patients after 10 years when compared to baseline (p
Published: 2020

19. Incidence and risk factors of pharyngocutaneus fistula formation after total laryngectomy. Review

Author: Else Kraemer-Baeza, Maria Dolores Aguilar-Conde, Cristina Isabel Sanz-Sánchez, Oscar Emilio Cazorla-Ramos, and Eva Flores-Carmona
Subjects: medicine.medical_specialty, Anemia, fpharyngocutaneous fistula, medicine.medical_treatment, Fistula, Energy Engineering and Power Technology, Pharyngocutaneous Fistula, Management Science and Operations Research, medicine, risk factors, Hypoalbuminemia, radiotherapy, business.industry, postlaryngectomy complications, Mechanical Engineering, Incidence (epidemiology), total laryngectomy, medicine.disease, Comorbidity, Surgery, Laryngectomy, Otorhinolaryngology, RF1-547, incidence, business, Complication
Abstract: Introduction and objective: The pharyngocutaneous fistula is a troublesome complication after total laryngectomy, increasing morbidity and mortality. We aimed to determine the incidence of pharyngocutaneus fistula after total laryngectomy and to define the possible predictors for pharyngocutaneus fistula formation. Method: We conducted a review of 31 articles with a total of 1100 patients, to evaluate the incidence of fistula in patients with total laryngectomy and risks factors involved. Results: The overall incidence of pharyngocutaneus fistula is 22,3%, and ranges from 3 to 65%. The review revealed that prior radiation treatment was the most common antecedent, following this associated comorbidity, hypoalbuminemia, anemia, and history of tracheotomy prior to laryngectomy. Discussion: Among the series studied, there is significant heterogeneity in the results, because although irradiated patients have a greater number of pharyngostomas, in some studies no relationship was found, which could explain the association with other risk factors. Conclusions: The incidence of pharyngocutaneus fistula is very variable and there are a large number of risk factors involved, the most frequent is radiotherapy associated or not with chemotherapy.
Published: 2020

20. When to transfuse your acute care patient? A narrative review of the risk of anemia and red blood cell transfusion based on clinical trial outcomes

Author: Katerina Pavenski, Ahmad Alli, Gregory M. T. Hare, Michael C. Sklar, Adriaan Van Rensburg, Jan O. Friedrich, Kyle Chin, Melina P Cazorla-Bak, C. David Mazer, Andrew J. Baker, S F Michelle Ku, and Nikhil Mistry
Subjects: medicine.medical_specialty, Blood management, Anemia, business.industry, General Medicine, Perioperative, 030204 cardiovascular system & hematology, medicine.disease, 3. Good health, law.invention, Clinical trial, 03 medical and health sciences, 0302 clinical medicine, Anesthesiology and Pain Medicine, Systematic review, Randomized controlled trial, 030202 anesthesiology, law, Anesthesiology, Anesthesia, Acute care, medicine, Intensive care medicine, business
Abstract: This narrative review critically evaluates the evidence for risk of anemia and red blood cell (RBC) transfusion. For this purpose, it assesses large prospective randomized-controlled trials (RCTs) in medical, surgical, and critical care patient populations in which the impact of specific hemoglobin transfusion thresholds are compared. In these trials, the risks of anemia relative to those of RBC transfusion are assessed. The results of published systematic reviews and meta-analyses are also discussed. Lastly, recommendations for patient blood management and treatment of anemia are explored. The main conclusion of this review emphasizes that the decision to transfuse RBCs is complex and depends on the interaction between multiple factors including the balance between the risk of anemia and the risk of RBC transfusion, existing patient comorbidities, and medical and surgical exposures. The transfusion thresholds recommended by current guidelines vary for medical and surgical patient populations. Guidelines suggesting specific transfusion thresholds for different patient populations should be viewed as a starting point for making an informed decision about RBC transfusion. Alternatives to transfusion (i.e., patient blood management), biomarkers of anemia-induced tissue hypoxia, and transfusion alternatives should continue to be evaluated in large RCTs, with the goal of improving event-free survival in critically ill and perioperative patients.
Published: 2020

21. Acute Renal Failure in Kidney Transplantation Due to Subcapsular Hematoma After a Renal Allograft Biopsy: Report of Two Cases and Literature Review

Author: Javier Naranjo, Juan Manuel Cazorla, Cristina León, María José Ledo, Teresa García, Auxiliadora Mazuecos, Manuel Ceballos, Ana García, and Florentino Villanego
Subjects: Adult, Male, medicine.medical_specialty, Biopsy, Kidney, urologic and male genital diseases, Postoperative Complications, medicine, Humans, Kidney transplantation, Aged, Hematoma, Transplantation, medicine.diagnostic_test, business.industry, Page kidney, Acute Kidney Injury, Allografts, medicine.disease, Subcapsular Hematoma, Kidney Transplantation, Surgery, surgical procedures, operative, Renal transplant, Renal allograft, Renal biopsy, business, Complication
Abstract: The compression of the renal parenchyma due to a subcapsular hematoma, also known as the "Page kidney," is a potentially serious but treatable complication of renal biopsy. Hypertension is very common and, in some cases, renal failure may be present. In kidney transplantation, it is a not well-described entity. Rapid intervention is essential to avoid irreversible damage of the graft and preserve its function. We report 2 cases of acute renal failure due to Page kidney in patients with renal transplant after a percutaneous biopsy with successful recovery after surgical treatment. In addition, we conducted a literature review in order to describe the clinical characteristics of this infrequent complication in patients with a history of renal transplant.
Published: 2020

22. Direct-Acting Antiretroviral Therapy in Renal Transplant Recipients With Human Immunodeficiency Virus–Hepatitis C Virus Coinfection: Report of Our Experience and Literature Review

Author: Florentino Villanego, Manuela Moreno-Ramírez, Javier Naranjo, Auxiliadora Mazuecos, Juan Manuel Cazorla, Teresa García, M. Jose Merino, and Luis Alberto Vigara
Subjects: Adult, Male, medicine.medical_specialty, Sustained Virologic Response, Sofosbuvir, Hepatitis C virus, Hepacivirus, Human immunodeficiency virus (HIV), Renal function, HIV Infections, medicine.disease_cause, Antiviral Agents, Postoperative Complications, Internal medicine, medicine, Humans, Transplantation, biology, Coinfection, business.industry, HIV, Middle Aged, medicine.disease, biology.organism_classification, Hepatitis C, Kidney Transplantation, Tacrolimus, Treatment Outcome, Female, Surgery, Liver function, business, medicine.drug
Abstract: A minor graft and patient survival are described in renal transplant recipients with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) coinfection than in recipients infected with only HIV. The high efficacy of direct-acting antivirals could improve the results. The experience reported in renal transplant recipients with coinfection is very limited. Material and Methods We analyzed the evolution of renal recipients with HIV-HCV coinfection treated with direct-acting antivirals in our center. Clinical, analytical, and microbiological variables were collected before and after treatment. Results From 2001 to 2018 we performed 11 renal transplants in patients with HIV infection, and 6 (54.5%) had HIV-HCV coinfection. One patient lost the graft before the development of direct-acting antivirals. Another patient with functioning graft has refused to receive any treatment. Four patients have been treated with direct-acting antivirals. One was treated 18 months before the transplant; 3 received treatment after transplant. All received sofosbuvir-based therapies. All had a sustained virologic response after 12 weeks and an improvement of liver function. In the patients treated after renal transplant, time post transplant at the beginning of treatment was 99.6 (SD, 22.8) months, and follow-up after treatment in all patients was 40.2 (SD, 8.16) months. To modify immunosuppressive regimen was not necessary, although 2 patients required an increase of tacrolimus doses. We do not observe deterioration of renal function. All have maintained a good immunologic and microbiological control without requiring changes in antiretrovirals. We do not observe complications associated with treatment. Conclusions Direct-acting antivirals therapy is safe and effective and may offer new possibilities to patients with HIV-HCV coinfection.
Published: 2020

23. Ceritinib plus Nivolumab in Patients with Advanced ALK-Rearranged Non–Small Cell Lung Cancer: Results of an Open-Label, Multicenter, Phase 1B Study

Author: Luojun Victor Wang, Yvonne Y. Lau, Thomas John, Giovanni Selvaggi, Filippo de Braud, Jeffrey W. Scott, Enriqueta Felip, Vanessa Giannone, O. Alejandro Balbin, Michela Maur, Daniel Shao-Weng Tan, Pilar Cazorla, Martijn P. Lolkema, Herbert H. Loong, Johan Vansteenkiste, Alice T. Shaw, Jason Baum, Geoffrey Liu, Medical Oncology, Institut Català de la Salut, [Felip E] Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. [de Braud FG] University of Milan, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. [Maur M] AOU Policlinico of Modena, University of Modena and Reggio Emilia, Modena, Italy. [Loong HH] The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China. [Shaw AT] Massachusetts General Hospital, Boston, Massachusetts. [Vansteenkiste JF] University Hospital KU Leuven, Leuven, Belgium, and Vall d'Hebron Barcelona Hospital Campus
Subjects: 0301 basic medicine, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Lung Neoplasms, medicine.medical_treatment, Ceritinib, NSCLC, Gastroenterology, Quimioteràpia combinada, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Carcinoma, Non-Small-Cell Lung, Internal medicine, PD-1, Maculopapular rash, medicine, Humans, Anaplastic Lymphoma Kinase, Other subheadings::/therapeutic use [Other subheadings], Sulfones, Pulmons - Càncer - Quimioteràpia, Lung cancer, Adverse effect, nivolumab, Chemotherapy, Otros calificadores::/uso terapéutico [Otros calificadores], business.industry, terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms::Bronchial Neoplasms::Carcinoma, Bronchogenic::Carcinoma, Non-Small-Cell Lung [DISEASES], neoplasias::neoplasias por localización::neoplasias torácicas::neoplasias del tracto respiratorio::neoplasias pulmonares::neoplasias de los bronquios::carcinoma broncogénico::carcinoma de pulmón de células no pequeñas [ENFERMEDADES], medicine.disease, Rash, Nivolumab, Pyrimidines, 030104 developmental biology, ALK, Oncology, 030220 oncology & carcinogenesis, Cohort, medicine.symptom, business, medicine.drug
Abstract: INTRODUCTION: Induction of programmed death ligand 1 (PD-L1) expression due to constitutive oncogenic signaling has been reported in NSCLC models harboring echinoderm microtubule associated protein like 4 gene (EML4)-ALK receptor tyrosine kinase gene (ALK) rearrangements. We assessed the safety and activity of ceritinib plus nivolumab in these patients. METHODS: In this open-label, phase 1B, multicenter, dose escalation and expansion study, previously treated (with ALK receptor tyrosine kinase [ALK] inhibitor [ALKI]/chemotherapy) or treatment-naive patients with stage IIIB or IV ALK-rearranged NSCLC received nivolumab, 3 mg/kg intravenously every 2 weeks, plus ceritinib, 450 mg/300 mg daily, with a low-fat meal. RESULTS: In total, 36 patients were treated (a 450-mg cohort [n=14] and a 300-mg cohort [n=22]). In the 450-mg cohort, four patients experienced dose-limiting toxicities. In the 300-mg cohort, two patients experienced dose-limiting toxicities. Among ALKI-naive patients, the overall response rate (ORR) was 83% (95% confidence interval [CI]: 35.9-99.6) in the 450-mg cohort and 60% (95% CI: 26.2-87.8) in the 300-mg cohort. Among ALKI-pretreated patients, the ORR was 50% (95% CI: 15.7-84.3) in the 450-mg cohort and 25% (95% CI: 5.5-57.2) in the 300-mg cohort. The ORR point estimate was observed to be greater in patients who were positive for PD-L1 than in those who were negative for PD-L1, with overlapping CIs (e.g., at a cutoff ≥1% PD-L1, 64% of patients [95% CI: 35.1-87.2] had confirmed responses as compared with those with negative PD-L1 staining (31% [95% CI: 11.0-58.7]). The most frequently reported grade 3 or 4 adverse events were increased alanine aminotransferase level (25%), increased gamma-glutamyl transferase level (22%), increased amylase level (14%), increased lipase level (11%), and maculopapular rash (11%). The incidence of all-grade rash (grouped term) was 64% in both cohorts; grade 3 rash was reported in 29% and 14% of patients in the 450-mg and 300-mg cohorts, respectively; no grade 4 rash was reported. CONCLUSION: Ceritinib plus nivolumab has activity; ORR appears to correlate with PD-L1 at baseline. Toxicity, especially rash, is more common than with either single agent. ispartof: Journal of Thoracic Oncology vol:15 issue:3 pages:392-403 ispartof: location:United States status: published
Published: 2020

24. Cardioprotective effect of sonic hedgehog ligand in pig models of ischemia reperfusion

Author: Maria Carmen Martinez, Alain Lacampagne, Bijan Ghaleh, Valérie Scheuermann, François Roubille, Raffaella Soleti, Jérôme Thireau, Lucien Sambin, Olivier Cazorla, Ramaroson Andriantsitohaina, Alain Bizé, UPEC, Ecole Nationale Veterinaire d’Alfort, Maisons-Alfort, France, Institut National de la Santé et de la Recherche Médicale (INSERM), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Stress Oxydant et Pathologies Métaboliques (SOPAM), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, medicine.medical_specialty, animal structures, Swine, [SDV]Life Sciences [q-bio], Ischemia, Myocardial Infarction, Myocardial Ischemia, Medicine (miscellaneous), Infarction, Myocardial Reperfusion Injury, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Enos, Internal medicine, medicine, Animals, Hedgehog Proteins, Myocardial infarction, cardiovascular diseases, Sonic hedgehog, Pharmacology, Toxicology and Pharmaceutics (miscellaneous), ComputingMilieux_MISCELLANEOUS, biology, business.industry, Myocardium, Arrhythmias, Cardiac, Heart, biology.organism_classification, medicine.disease, 3. Good health, 030104 developmental biology, Coronary occlusion, Concomitant, embryonic structures, Ventricular fibrillation, biology.protein, Cardiology, cardiovascular system, business, arrhythmias, Anti-Arrhythmia Agents, Research Paper
Abstract: International audience; Sonic hedgehog (SHH) signaling pathway is involved in embryonic tissue patterning and development. Our previous work identified, in small rodent model of ischemia reperfusion, SHH as a specific efficient tool to reduce infarct size and subsequent arrhythmias by preventing ventricular repolarization abnormalities. The goal of the present study was to provide a proof of concept of the cardioprotective effect of SHH ligand in a porcine model of acute ischemia. Methods: The antiarrhythmic effect of SHH, either by a recombinant peptide (N-SHH) or shed membrane microparticles harboring SHH ligand (MPs SHH+), was evaluated in a first set of pigs following a short (25 min) coronary artery occlusion (CAO) followed by 24 hours-reperfusion (CAR) (Protocol A). The infarct-limiting effect was evaluated on a second set of pigs with 40 min of coronary artery occlusion followed by 24 hours reperfusion (Protocol B). Electrocardiogram (ECG) was recorded and arrhythmia's scores were evaluated. Area at risk and myocardial infarct size were quantified. Results: In protocol A, administration of N-SHH 15 min. after the onset of coronary occlusion significantly reduced the occurrence of ventricular fibrillation compared to control group. Evaluation of arrhythmic score showed that N-SHH treatment significantly reduced the overall occurrence of arrhythmias. In protocol B, massive infarction was observed in control animals. Either N-SHH or MPs SHH+ treatment reduced significantly the infarct size with a concomitant increase of salvaged area. The reduction in infarct size was both accompanied by a significant decrease in systemic biomarkers of myocardial injury, i.e., cardiac troponin I and fatty acid-binding protein and an increase of eNOS activation. Conclusions: We show for the first time in a large mammalian model that the activation of the SHH pathway by N-SHH or MPs SHH+ offers a potent protection of the heart to ischemia-reperfusion by preventing the reperfusion arrhythmias, reducing the infarct area and the circulating levels of biomarkers for myocardial injury. These data open up potentially theranostic prospects for patients suffering from myocardial infarction to prevent the occurrence of arrhythmias and reduce myocardial tissue damage.
Published: 2020

25. Molybdenum Cofactor Deficiency: Mega Cisterna Magna in Two Consecutive Pregnancies and Review of the Literature

Author: M C Alonzo Martínez, Eduardo Cazorla, Alejandro Cores, Alfons Serrano, Esther Cánovas, and K Anniuk
Subjects: 0301 basic medicine, business.industry, Encephalopathy, Physiology, Prenatal diagnosis, Gene mutation, medicine.disease, Enlarged cisterna magna, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, chemistry, Inborn error of metabolism, Genetics, medicine, Molybdenum cofactor, business, Sulfite oxidase deficiency, Molybdenum cofactor deficiency, 030217 neurology & neurosurgery, Genetics (clinical)
Abstract: The molybdenum cofactor deficiency is an autosomal recessive disease, characterized by rapidly progressive and severe neurological damage that mimics a hypoxic-ischemic encephalopathy due to the accumulation of toxic metabolites that cause rapid neurodegeneration after the delivery. It is eventually lethal, in a similar way to the rare isolated sulfite oxidase deficiency. This serious pathology usually causes death in the immediate neonatal period in the more severe variants. We report a case of two consecutive pregnancies with enlarged cisterna magna as the only prenatal pathological finding since 26 weeks of gestation (WG) and the subsequent death of the newborns in the first week after birth. After the second pregnancy, we reached the diagnosis of molybdenum cofactor deficiency due to MOCS1 gene mutation. According to the cases reported in the literature, this is the case with the earliest neuroimage prenatal findings.
Published: 2020

26. Screening for in-vivo regional contractile defaults to predict the delayed Doxorubicin Cardiotoxicity in Juvenile Rat

Author: Laure Saumet, Stefan Matecki, Nourdine Chakouri, Nicolas Sirvent, Pascal Amedro, Laurence Vergely, Charlotte Farah, Olivier Cazorla, Marie Vincenti, Alain Lacampagne, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université Catholique de Louvain = Catholic University of Louvain (UCL), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Arnaud de Villeneuve [CHRU Montpellier], and MORNET, Dominique
Subjects: Male, myofilament, Cardiomyopathy, heart failure, Medicine (miscellaneous), Speckle tracking echocardiography, 030204 cardiovascular system & hematology, Ventricular Function, Left, 0302 clinical medicine, Cancer Survivors, Neoplasms, regional speckle tracking echocardiography, Myocytes, Cardiac, Anthracyclines, Longitudinal Studies, Pharmacology, Toxicology and Pharmaceutics (miscellaneous), Antibiotics, Antineoplastic, Ejection fraction, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Echocardiography, 030220 oncology & carcinogenesis, Injections, Intravenous, Cardiology, Research Paper, Cardiac function curve, medicine.medical_specialty, [SDV.SP.MED] Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Anthracycline, Heart Ventricles, cardiotoxicity, Protein degradation, 03 medical and health sciences, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, Animals, Humans, Rats, Wistar, Cardiotoxicity, business.industry, Stroke Volume, medicine.disease, Myocardial Contraction, Rats, Disease Models, Animal, Doxorubicin, Heart failure, business
Abstract: International audience; Anthracyclines are key chemotherapeutic agents used in various adult and pediatric cancers, however, their clinical use is limited due to possible congestive heart failure (HF) caused by acute and irreversible cardiotoxicity. Currently, there is no method to predict the future development of the HF in these patients. In order to identify early biomarkers to predict anthracycline cardiotoxicity in long-term survivors of childhood cancer, this longitudinal study aimed to analyze early and late in-vivo regional myocardial anthracycline-induced cardiotoxicity, related to in-vitro cardiac myocytes dysfunction, in a juvenile rat model.Methods: Young male Wistar rats (4 weeks-old) were treated with different cumulative doses of doxorubicin (7.5, 10 or 12.5 mg/kg) or NaCl (0.9%) once a week for 6 weeks by intravenous injection. Cardiac function was evaluated in-vivo by conventional (left ventricular ejection fraction, LVEF) and regional two-dimensional (2D) speckle tracking echocardiography over the 4 months after the last injection. The animals were assigned to preserved (pEF) or reduced EF (rEF) groups at the end of the protocol and were compared to controls.Results: We observed a preferential contractile dysfunction of the base of the heart, further altered in the posterior segment, even in pEF group. The first regional alterations appeared 1 month after chemotherapy. Functional investigation of cardiomyocytes isolated from the LV base 1 month after doxorubicin treatment showed that early in-vivo contractile alterations were associated with both decreased myofilament Ca2+ sensitivity and length-dependent activation. Changes in post-translational modifications (phosphorylation; S-glutathionylation) and protein degradation of the cardiac myosin binding protein-C may contribute to these alterations.Conclusion: Our data suggest that screening of the contractile defaults of the base of the heart by regional 2D strain echocardiography is useful to detect subclinical myocardial dysfunction prior to the development of delayed anthracycline-induced cardiomyopathy in pediatric onco-cardiology.
Published: 2020

27. Implementation of second-tier tests in newborn screening for the detection of vitamin B12 related acquired and genetic disorders: results on 258,637 newborns

Author: Sonia Pajares, Aleix Navarro-Sastre, Laura Gort, Silvia Meavilla, José Antonio Arranz, Mireia del Toro, Clara Carnicer, M. Santos, Frederic Tort, Antonia Ribes, Judit García-Villoria, Rafael Artuch, José Luis Marín, Camila García-Volpe, Ana Argudo, José Manuel González de Aledo-Castillo, Rosa Fernández, R.M. López, Aida Ormazabal, Angeles Garcia-Cazorla, Institut Català de la Salut, [Pajares S] Sección de Errores Congénitos del Metabolismo IBC, Servicio de Bioquímica y Genética Molecular, Hospital Clínic de Barcelona, 08028 Barcelona, Spain. Center for Biomedical Research Network on Rare Diseases (CIBERER), Madrid, Spain. [Arranz JA, Del Toro M, Carnicer C] Unitat de Malalties Metabòliques Hereditàries, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Ormazabal A, García-Cazorla Á] Center for Biomedical Research Network on Rare Diseases (CIBERER), Madrid, Spain. Inborn Errors of Metabolism Unit, Hospital Sant Joan de Déu, Barcelona, Spain. [Navarro-Sastre A] Sección de Errores Congénitos del Metabolismo IBC, Servicio de Bioquímica y Genética Molecular, Hospital Clínic de Barcelona, 08028 Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Newborn screening, Pediatrics, medicine.medical_specialty, Anemia, Methylmalonic acidemia, Methylmalonic acid, Congenital, Hereditary, and Neonatal Diseases and Abnormalities [DISEASES], Homocystinuria, Cobalamin, enfermedades y anomalías neonatales congénitas y hereditarias::enfermedades genéticas congénitas::alteraciones congénitas del metabolismo::alteraciones congénitas del metabolismo de los aminoácidos::acidemia propiónica [ENFERMEDADES], 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, 030225 pediatrics, medicine, Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Genetic Diseases, Inborn::Metabolism, Inborn Errors::Amino Acid Metabolism, Inborn Errors::Propionic Acidemia [DISEASES], Infants nadons, Pharmacology (medical), Vitamin B12, Propionic acidemia, Homocysteine, Genetics (clinical), business.industry, Aminoàcids - Metabolisme - Trastorns, personas::Grupos de Edad::lactante::recién nacido [DENOMINACIONES DE GRUPOS], nutritional and metabolic diseases, General Medicine, enfermedades y anomalías neonatales congénitas y hereditarias [ENFERMEDADES], medicine.disease, Persons::Age Groups::Infant::Infant, Newborn [NAMED GROUPS], Second-tier test, Vitamin B12 deficiency, chemistry, Methylcitric acid, Medicine, Metabolisme, Errors congènits del, business, 030217 neurology & neurosurgery
Abstract: Background Alteration of vitamin B12 metabolism can be genetic or acquired, and can result in anemia, failure to thrive, developmental regression and even irreversible neurologic damage. Therefore, early diagnosis and intervention is critical. Most of the neonatal cases with acquired vitamin B12 deficiency have been detected by clinical symptoms and only few of them trough NBS programs. We aim to assess the usefulness of the second-tier test: methylmalonic acid (MMA), methylcitric acid (MCA) and homocysteine (Hcys) in our newborn screening program and explore the implications on the detection of cobalamin (vitamin B12) related disorders, both genetic and acquired conditions. Methods A screening strategy using the usual primary markers followed by the analysis of MMA, MCA and Hcys as second tier-test in the first dried blood spot (DBS) was developed and evaluated. Results During the period 2015–2018 a total of 258,637 newborns were screened resulting in 130 newborns with acquired vitamin B12 deficiency (incidence 1:1989), 19 with genetic disorders (incidence 1:13,613) and 13 were false positive. No false negatives were notified. Concerning the second-tier test, the percentage of cases with MMA above the cut-off levels, both for genetic and acquired conditions was very similar (58% and 60%, respectively). Interestingly, the percentage of cases with increased levels of Hcys was higher in acquired conditions than in genetic disorders (87% and 47%, respectively). In contrast, MCA was high only in 5% of the acquired conditions versus in 53% of the genetic disorders, and it was always very high in all patients with propionic acidemia. Conclusions When screening for methylmalonic acidemia and homocystinuria, differential diagnosis with acquired vitamin B12 deficiency should be done. The results of our strategy support the inclusion of this acquired condition in the NBS programs, as it is easily detectable and allows the adoption of corrective measures to avoid the consequences of its deficiency.
Published: 2021

28. Novel Protein Biomarkers of Monoamine Metabolism Defects Correlate with Disease Severity

Author: Beat Thöny, Alba Tristán-Noguero, Gabriella Horvath, Zuhal Yapici, Tessa M. A. Peters, Roser Pons, Kathrin Jeltsch, Tessa Wassenberg, Keith Hyland, Guillermo Agosta, Jennifer Friedman, Michèl A.A.P. Willemsen, Eduardo López-Laso, Thomas Opladen, Eduard Sabidó, Eva Borràs, Angels García-Cazorla, Rafael Artuch, Marta Molero-Luis, Marcel M. Verbeek, Pediatrics, University of Zurich, and García‐Cazorla, Àngels
Subjects: 0301 basic medicine, Proteomics, Apolipoprotein D, Movement disorders, early parkinsonism, 610 Medicine & health, neurotransmitters, Severity of Illness Index, cerebrospinal fluid, 03 medical and health sciences, 0302 clinical medicine, proteomics, medicine, Humans, Tetrahydrobiopterin deficiency, Amino Acid Metabolism, Inborn Errors, Dystonia, biomarkers, Tyrosine hydroxylase, business.industry, Parkinsonism, Dopaminergic, medicine.disease, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], 2728 Neurology (clinical), 030104 developmental biology, Monoamine neurotransmitter, Neurology, 10036 Medical Clinic, Dystonic Disorders, 2808 Neurology, Immunology, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery, Biomarkers
Abstract: BACKGROUND: Genetic defects of monoamine neurotransmitters are rare neurological diseases amenable to treatment with variable response. They are major causes of early parkinsonism and other spectrum of movement disorders including dopa-responsive dystonia. OBJECTIVES: The objective of this study was to conduct proteomic studies in cerebrospinal fluid (CSF) samples of patients with monoamine defects to detect biomarkers involved in pathophysiology, clinical phenotypes, and treatment response. METHODS: A total of 90 patients from diverse centers of the International Working Group on Neurotransmitter Related Disorders were included in the study (37 untreated before CSF collection, 48 treated and 5 unknown at the collection time). Clinical and molecular metadata were related to the protein abundances in the CSF. RESULTS: Concentrations of 4 proteins were significantly altered, detected by mass spectrometry, and confirmed by immunoassays. First, decreased levels of apolipoprotein D were found in severe cases of aromatic L-amino acid decarboxylase deficiency. Second, low levels of apolipoprotein H were observed in patients with the severe phenotype of tyrosine hydroxylase deficiency, whereas increased concentrations of oligodendrocyte myelin glycoprotein were found in the same subset of patients with tyrosine hydroxylase deficiency. Third, decreased levels of collagen6A3 were observed in treated patients with tetrahydrobiopterin deficiency. CONCLUSION: This study with the largest cohort of patients with monoamine defects studied so far reports the proteomic characterization of CSF and identifies 4 novel biomarkers that bring new insights into the consequences of early dopaminergic deprivation in the developing brain. They open new possibilities to understand their role in the pathophysiology of these disorders, and they may serve as potential predictors of disease severity and therapies. © 2020 International Parkinson and Movement Disorder Society.
Published: 2021

29. Assessment of intellectual impairment, health-related quality of life, and behavioral phenotype in patients with neurotransmitter related disorders: Data from the iNTD registry

Author: Stacey Tay Kiat Hong, Georg F. Hoffmann, Angeles Garcia-Cazorla, Suet-Na Wong, Jan Kulhánek, Mareike Keller, Heiko Brennenstuhl, Oya Kuseyri Hübschmann, Yilmaz Yildiz, Mari Oppebøen, Kathrin Jeltsch, Francesca Manzoni, H. Serap Sivri, Alberto Burlina, Saadet Mercimek-Andrews, Elisenda Cortès-Saladelafont, Dimitrios I. Zafeiriou, Sven F. Garbade, Thomas Opladen, Pablo Mir, Jennifer Friedman, Vincenzo Leuzzi, Joaquín Alejandro Fernández Ramos, Mario Mastrangelo, Eduardo López-Laso, Jeanette Koht, Dora Steel, Toni S. Pearson, Natalia Alexandra Julia Palacios, Filippo Manti, Thomas Lücke, Tomas Honzik, Jesus Serrano-Lomelin, Galina Stevanović, Ivana Kavecan, Cheuk-Wing Fung, Manju A. Kurian, Roser Pons, Helly Goez, and University of Heidelberg
Subjects: Succinic semialdehyde dehydrogenase deficiency, Male, Internationality, Intelligence, 0302 clinical medicine, Quality of life, Neurotransmitter deficiencies, Neurotransmitter metabolism, Registries, Child, Genetics (clinical), behavioral phenotype, cognitive impairment, intelligence, quality of life, iNTD, Psychomotor learning, 0303 health sciences, Neurotransmitter Agents, Intelligence quotient, Middle Aged, 3. Good health, neurotransmitter deficiencies, Phenotype, Cognitive impairment, Child, Preschool, Anxiety, Female, medicine.symptom, Clinical psychology, Adult, Behavioral phenotype, Adolescent, Attention span, 03 medical and health sciences, Young Adult, Genetics, medicine, Humans, Cognitive Dysfunction, 030304 developmental biology, Behavior, business.industry, Neurotransmitterdeficiencies, Infant, medicine.disease, Sepiapterin reductase deficiency, business, 030217 neurology & neurosurgery
Abstract: Inherited disorders of neurotransmitter metabolism are a group of rare diseases, which are caused by impaired synthesis, transport, or degradation of neurotransmitters or cofactors and result in various degrees of delayed or impaired psychomotor development. To assess the effect of neurotransmitter deficiencies on intelligence, quality of life, and behavior, the data of 148 patients in the registry of the International Working Group on Neurotransmitter Related Disorders (iNTD) was evaluated using results from standardized age-adjusted tests and questionnaires. Patients with a primary disorder of monoamine metabolism had lower IQ scores (mean IQ 58, range 40-100) within the range of cognitive impairment (, Dietmar Hopp Stiftung (DE); Medical Faculty of the University of Heidelberg.
Published: 2021

30. Feasibility and acceptability of personalised breast cancer screening (DECIDO study): protocol of a single-arm proof-of-concept trial

Author: Marta Hernandez, Anna Pons-Rodriguez, Carles Forné Izquierdo, Jordi Vilaplana-Mayoral, Inés Cruz-Esteve, Isabel Sánchez-López, Mercè Reñé-Reñé, Cristina Cazorla, Marta Hernández-Andreu, Gisela Galindo-Ortego, Montserrat Llorens Gabandé, Celmira Laza-Vásquez, Pau Balaguer-Llaquet, Montserrat Martínez-Alonso, Montserrat Rué, Iván-David Benítez, Alexandra Bertran, Àngels Cardona, Misericòrdia Carles-Lavila, Cristina Cazorla-Sánchez, Núria Codern, Carles Forné-Izquierdo, Maria José Hernández-Andreu, Edelmir Iglesias, Montserrat Llorens-Gabandé, Maria José Pérez-Lacasta, and Hèctor Perpiñán
Subjects: Adult, medicine.medical_specialty, Breast Cancer Surveillance Consortium, Breast Neoplasms, breast tumours, Breast cancer screening, Breast cancer, Cancer screening, medicine, Humans, Early Detection of Cancer, Research ethics, medicine.diagnostic_test, business.industry, public health, Absolute risk reduction, health policy, Bayes Theorem, General Medicine, Middle Aged, medicine.disease, Spain, Family medicine, Good clinical practice, Medicine, Feasibility Studies, epidemiology, Female, Breast disease, Health Services Research, business
Abstract: Introduction Personalised cancer screening aims to improve benefits, reduce harms and being more cost-effective than age-based screening. The objective of the DECIDO study is to assess the acceptability and feasibility of offering risk-based personalised breast cancer screening and its integration in regular clinical practice in a National Health System setting. Methods and analysis The study is designed as a single-arm proof-of-concept trial. The study sample will include 385 women aged 40-50 years resident in a primary care health area in Spain. The study intervention consists of (1) a baseline visit; (2) breast cancer risk estimation; (3) a second visit for risk communication and screening recommendations based on breast cancer risk and (4) a follow-up to obtain the study outcomes. A polygenic risk score (PRS) will be constructed as a composite likelihood ratio of 83 single nucleotide polymorphisms. The Breast Cancer Surveillance Consortium risk model, including age, race/ethnicity, family history of breast cancer, benign breast disease and breast density will be used to estimate a preliminary 5-year absolute risk of breast cancer. A Bayesian approach will be used to update this risk with the PRS value. The primary outcome measures will be attitude towards, intention to participate in and satisfaction with personalised breast cancer screening. Secondary outcomes will include the proportions of women who accept to participate and who complete the different phases of the study. The exact binomial and the Student's t-test will be used to obtain 95% CIs. Ethics and dissemination The study protocol was approved by the Drug Research Ethics Committee of the University Hospital Arnau de Vilanova. The trial will be conducted in compliance with this study protocol, the Declaration of Helsinki and Good Clinical Practice. The results will be published in peer-reviewed scientific journals and disseminated in scientific conferences and media. Trial registration number NCT03791008. This study was supported by the research grant 'Personalized breast cancer screening: assessment of its feasibility and acceptability in the National Health System' (PI17/00834) from the Instituto de Salud Carlos III and cofunded by Fondo Europeo de Desarrollo Regional (FEDER) 'Una manera de hacer Europa'. Celmira Laza Vásquez received a grant from Santander Program scholarship 2020 as a predoctoral fellow at the University of Lleida. The non-profit organisation Oncolliga Lleida (grant number N/A) will fund part of the genomic analyses for breast cancer risk assessment.
Published: 2020

31. Flying Fox Hemolytic Fever, Description of a New Zoonosis Caused by Candidatus Mycoplasma haemohominis

Author: Denise Desoutter, Julien Colot, Elise Klement-Frutos, Cécile Cazorla, Vincent Bossi, Pierre-Edouard Fournier, Malik Oedin, Bernard Davoust, Elodie Descloux, Anthony Levasseur, Sylvie Laumond, Martine Chauvet, Isabelle Mermoud, Didier Raoult, Ann-Claire Gourinat, Oleg Mediannikov, A. Merlet, Fabrice Brescia, Marie-Amélie Goujart, Luca Antonini, Centre hospitalier territorial Gaston-Bourret [Dumbea] (CHT), Centre hospitalier territorial Gaston-Bourret [Nouméa], Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Marseille (APHM), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Groupe Bactériologie Expérimentale [Nouméa, Nouvelle-Calédonie], Institut Pasteur de Nouvelle-Calédonie, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Direction des Affaires Vétérinaires, Alimentaires et Rurales (DAVAR), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Institut Agronomique Néo-Calédonien (IAC), Direction des Affaires sanitaires et sociales de la Nouvelle-Calédonie [Nouméa] (DASS [Nouméa]), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), This work was supported by Public Health Funds from New Caledonia, the Méditerranée-Infection Foundation and the French Agence Nationale de la Recherche under reference Investissements d’Avenir Méditerranée Infection 10-IAHU-03, and Région Provence-Alpes-Côte d’Azur and European funding Fonds européen de développement régional (FEDER) IHUBIOTK., ANR-10-IAHU-0003,Méditerranée Infection,I.H.U. Méditerranée Infection(2010), and Institut de Recherche Biomédicale des Armées (IRBA)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)
Subjects: 0301 basic medicine, Microbiology (medical), Anemia, 030106 microbiology, bats, medicine.disease_cause, 03 medical and health sciences, MESH: Mycoplasma, Mycoplasma, New Caledonia, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Chiroptera, medicine, Flying fox (fish), Animals, Humans, Mycoplasma Infections, MESH: Animals, MESH: Phylogeny, Phylogeny, autoimmune hemolytic anemia, Retrospective Studies, hemophagocytosis, Candidatus Mycoplasma haemohominis, MESH: Humans, biology, business.industry, Zoonosis, MESH: Chiroptera, MESH: Retrospective Studies, MESH: Mycoplasma Infections, medicine.disease, biology.organism_classification, Pteropus, Virology, 3. Good health, Nycteribiidae, 030104 developmental biology, Infectious Diseases, Candidatus, Autoimmune hemolytic anemia, business
Abstract: Background Hemotropic mycoplasmas, previously classified in the genus Eperythrozoon, have been reported as causing human infections in Brazil, China, Japan, and Spain. Methods In 2017, we detected DNA from Candidatus Mycoplasma haemohominis in the blood of a Melanesian patient from New Caledonia presenting with febrile splenomegaly, weight loss, life-threatening autoimmune hemolytic anemia, and hemophagocytosis. The full genome of the bacterium was sequenced from a blood isolate. Subsequently, we retrospectively (2011–2017) and prospectively (2018–2019) tested patients who had been hospitalized with a similar clinico-biological picture. In addition, as these patients had been in contact with frugivorous bats (authorized under conditions for hunting and eating in New Caledonia), we investigated the role of these animals and their biting flies by testing them for hemotropic mycoplasmas. Results There were 15 patients found to be infected by this hemotropic mycoplasma. Among them, 4 (27%) died following splenectomy performed either for spontaneous spleen rupture or to cure refractory autoimmune hemolytic anemia. The bacterium was cultivated from the patient’s blood. The full genome of the Neocaledonian Candidatus M. haemohominis strain differed from that of a recently identified Japanese strain. Of 40 tested Pteropus bats, 40% were positive; 100% of collected bat flies Cyclopodia horsfieldi (Nycteribiidae, Diptera) were positive. Human, bat, and dipteran strains were highly similar. Conclusions The bacterium being widely distributed in bats, Candidatus M. haemohominis, should be regarded as a potential cause of severe infections in humans.
Published: 2021

32. Author Correction: The utility of Next Generation Sequencing for molecular diagnostics in Rett syndrome

Author: Nuria Brandi, Angels García-Cazorla, Jean-Rémi Trotta, Maria del Mar O’Callaghan, Sophia Derdak, Mercè Pineda, Laura Blasco, Edgar Gerotina, Judith Armstrong, Silvia Vidal, and Paola Pacheco
Subjects: DNA Copy Number Variations, Methyl-CpG-Binding Protein 2, Science, MEDLINE, Nerve Tissue Proteins, Rett syndrome, Computational biology, Protein Serine-Threonine Kinases, Polymorphism, Single Nucleotide, DNA sequencing, Cohort Studies, Exome Sequencing, Rett Syndrome, Humans, Medicine, Genetic Testing, Author Correction, Multidisciplinary, business.industry, High-Throughput Nucleotide Sequencing, Forkhead Transcription Factors, medicine.disease, Molecular diagnostics, Mutation, business
Abstract: Rett syndrome (RTT) is an early-onset neurodevelopmental disorder that almost exclusively affects girls and is totally disabling. Three genes have been identified that cause RTT: MECP2, CDKL5 and FOXG1. However, the etiology of some of RTT patients still remains unknown. Recently, next generation sequencing (NGS) has promoted genetic diagnoses because of the quickness and affordability of the method. To evaluate the usefulness of NGS in genetic diagnosis, we present the genetic study of RTT-like patients using different techniques based on this technology. We studied 1577 patients with RTT-like clinical diagnoses and reviewed patients who were previously studied and thought to have RTT genes by Sanger sequencing. Genetically, 477 of 1577 patients with a RTT-like suspicion have been diagnosed. Positive results were found in 30% by Sanger sequencing, 23% with a custom panel, 24% with a commercial panel and 32% with whole exome sequencing. A genetic study using NGS allows the study of a larger number of genes associated with RTT-like symptoms simultaneously, providing genetic study of a wider group of patients as well as significantly reducing the response time and cost of the study.
Published: 2021

33. A Prospective Cohort Study to Identify Clinical, Biological, and Imaging Features That Predict the Etiology of Acute Encephalitis

Author: Daniel Da Silva, Vincent Roubeau, Patricia Pavese, Jean-Paul Mira, Rafael Mahieu, Heidi Wille, Lydie Khatchatourian, Charlotte Biron, Geneviève Blanchet-Fourcade, Romain Lefaucheur, Laurent Argaud, Arnaud Seigneurin, Guillaume Baille, Eugénie Mutez, Hélène Brasme, Morgan Matt, Amandine Gagneux-Brunon, Alexandra Mailles, Thibaut Fraisse, Morgane Le Bras, Céline Cazorla, Isabelle Pierre, Anne Bonnetain, Hélène Savini, Nathalie Marin, Isabelle Runge, Pierre Fillatre, Mathilde Reveillon-Istin, Mathieu Godement, Cédric Bruel, Martin Martinot, Xavier Argemi, Saber Touati, Emmanuel Forestier, M. Hentzien, Jérome Honnorat, Capucine Diard-Detoeuf, Nathalie Pansu, Yvon Ruch, Thècle Degroote, Alexandre Mas, Guillaume Louis, Bernard Castan, Thomas Guimard, Aurélien Dinh, Marc-Olivier Vareil, Pierre Jaquet, Aurélie Richard-Mornas, Thibault Challan-Belval, Paul Le Turnier, Aurélie Martin, Frédéric Bourdain, Catherine Chirouze, Pascal Chavanet, Carole Henry, François Goehringer, Alain Makinson, Fabrice Bruneel, Anne Pachart, Manuela Le Cam, Johan Courjon, Elisabeth Botelho-Nevers, Pierre Tattevin, Emilie Piet, Eric Denes, Jean-Louis Herrmann, Philippe Casenave, Rodolphe Buzele, Marion Le Maréchal, Laurence Maulin, Thomas De Broucker, Agnès Riché, Sylvain Rheims, Olivier Epaulard, Solene Patrat-Delon, Aurélie Baldolli, Valentin Greigert, Isabelle Gueit, Anne-Sophie Lecompte, Nicolas Gaillard, Marie Froidure, Guillaune Marc, Dimitri Psimaras, Nathalie Asseray, Charles Cazanave, Etienne Canouï, Jean-Etienne Herbrecht, Alexandre Thibault Jacques Maria, Romain Sonneville, Patrice Morand, Jessica Krause, Jean-Marie Turmel, Tomasz Tchroboczek, Kelly Tiercelet, Gwenael Le Moal, Arnaud de la Blanchardiere, Thomas Baudry, Jean-Paul Stahl, Simon Gravier, Frédéric Méchaï, Diane Ponscarme, Christelle Lucas, Laurent Almoyna-Martinez, Colin Deschanvres, Olivier Lesieur, Véronique Pelonde-Erimée, Raphaël Lecomte, David Boutoille, Sophie Abgrall, Jérémie Orain, Philippe Lesprit, François Raffi, Magalie Vidal-Roux, Mathieu Blot, Michael Bonnan, Arnaud Galbois, V. Vitrat, Olivier Bouchaud, Guillaume Martin-Blondel, Mathieu Zuber, Stéphanie Lejeune, Solen Kernéis, Hélène Pellerin, Isabelle Tyvaert, Mathilde Puges, Xavier Lescure, Philippe Mateu, Marine Delaroche, Fanny Jomier, Julien Biberon, Pascale Goubin, Benjamin Gaborit, Etienne De Montmollin, Centre Hospitalier Universitaire [Grenoble] (CHU), Santé publique France - French National Public Health Agency [Saint-Maurice, France], CHU Pontchaillou [Rennes], ARN régulateurs bactériens et médecine (BRM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), French Infectious Diseases Society, and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Infectious Encephalitis, 0301 basic medicine, Microbiology (medical), Herpesvirus 3, Human, Pediatrics, medicine.medical_specialty, Lymphocytosis, diagnosis, viruses, encephalitis, etiology, [SDV]Life Sciences [q-bio], 030106 microbiology, factor analysis, Context (language use), medicine.disease_cause, Virus, 03 medical and health sciences, 0302 clinical medicine, medicine, Infectious encephalitis, Humans, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, business.industry, medicine.disease, herpes simplex virus, 3. Good health, Infectious Diseases, Herpes simplex virus, Etiology, Encephalitis, Herpes Simplex, France, medicine.symptom, business, Encephalitis
Abstract: Background New diagnostic tools have been developed to improve the diagnosis of infectious encephalitis. Using a prospective cohort of encephalitis patients, our objective was to identify possible clusters of patients with similar patterns among encephalitis of unknown cause (EUC) and to describe to what extent a patient’s initial presentation may be predictive of encephalitis etiology, particularly herpes simplex virus (HSV) and varicella-zoster virus (VZV). Methods The National Cohort of Infectious Encephalitis in France is an ongoing prospective cohort study implemented in France in 2016. Patients who present with documented or suspected acute infectious encephalitis were included. Focusing on the variables that describe the initial presentation, we performed a factor analysis of mixed data (FAMD) to investigate a pattern of association between the initial presentation of a patient and the etiologic pathogen. Results As of 1 August 2018, data from 349 patients were analyzed. The most frequent pathogens were HSV (25%), VZV (11%), tick-borne encephalitis virus (6%), Listeria (5%), influenza virus (3%), and EUC (34%). Using the FAMD, it was not possible to identify a specific pattern related to the group of EUC. Age, temporal or hemorrhagic lesions, and cerebral spinal fluid lymphocytosis were significantly associated with HSV/VZV encephalitis. Conclusions No initial clinical/imaging/biology pattern was identified at admission among EUC, despite the improvement in diagnostic tools. In this context, the recommendation for a universal, early, probabilistic, initial treatment against HSV and VZV is still relevant, regardless of the initial clinical presentation of the encephalitis.
Published: 2021

34. P074 In vitro and in vivo efficacy of linezolid on Treponema pallidum, the syphilis agent

Author: Oriol Mitjà, Llorenç Quintó, C Nieto, Emily Romeis, M Vall Mayans, Lorenzo Giacani, M Ubals Cazorla, Clara Pérez-Mañá, and Austin M. Haynes
Subjects: Treponema, biology, business.industry, biology.organism_classification, medicine.disease, Virology, In vitro, chemistry.chemical_compound, chemistry, In vivo, Linezolid, Medicine, Syphilis, business
Published: 2021

35. P394 Evaluation of the in vitro efficacy of cefixime, dalbavancin, isoniazid, and pyrazinamide against Treponema pallidum

Author: M Vall Mayans, Lauren C. Tantalo, C Nieto, Llorenç Quintó, Oriol Mitjà, M Ubals Cazorla, Lorenzo Giacani, and Clara Pérez-Mañá
Subjects: Treponema, biology, medicine.drug_class, business.industry, Antibiotics, Isoniazid, Dalbavancin, Glycopeptide antibiotic, Pyrazinamide, medicine.disease, biology.organism_classification, Microbiology, medicine, Syphilis, business, Cefixime, medicine.drug
Abstract: Background The shortage in the supply of benzathine penicillin G (BPG) and other limitations associated with BPG use underscore the need for new therapeutic options for syphilis treatment. Until recently, Treponema pallidum (T. pallidum), the syphilis agent, could not be cultured in vitro, making the screening of antibiotics only possible in vivo, and hence difficult, time-consuming, and expensive. Because a cultivation system for this difficult pathogen is now available, we used an in vitro minimum inhibitory concentration (MIC) assay to screen antibiotics with the potential to provide new treatment options for syphilis. Methods T. pallidum was cultured in vitro in the presence of multiple concentrations of cefixime, dalbavancin, isoniazid, and pyrazinamide in independent experiments. All these antibiotics have adequate pharmacokinetic and pharmacodynamic properties to treat syphilis based on previous data from humans studies in other infections. After seven days in culture, DNA was extracted from the culture wells and T. pallidum growth was compared to no-antibiotic culture wells using qPCR targeting the tp0574 gene. Results Isoniazid and pyrazinamide, both antimycobacterials, had MICs of >500ng/ml and >64μg/ml, respectively. For cefixime, a cephalosporin, and dalbavancin, a glycopeptide antibiotic, the experimental MICs were Conclusion Cefixime and dalbavancin appear to have marked microbicidal activity against T. pallidum with MICs that make them promising candidates for syphilis treatment in place of BPG. Isoniazid and pyrazinamide showed no significant treponemacidal activity in vitro at the concentrations tested.
Published: 2021

36. [Utilization study in real clinical practice of ceftolozane/tazobactam vs aminoglycosides and/or colistin in the treatment of multirresistant or extremely resistant Pseudomonas aeruginosa]

Author: M Pérez-Moreno, A Pinilla-Rello, I Larrodé-Leciñena, A Magallón-Martínez, L Cazorla-Poderoso, R Huarte-Lacunza, R M Martínez-Álvarez, A I López-Calleja, and O Pereira-Blanco
Subjects: Microbiology (medical), Male, medicine.medical_specialty, Tazobactam, medicine.drug_class, Original, ceftolozane/tazobactam, Antibiotics, Aftercare, Microbial Sensitivity Tests, colistina, ceftolozano/tazobactam, Internal medicine, Drug Resistance, Multiple, Bacterial, medicine, Humans, Pseudomonas Infections, Prospective Studies, colistin, Prospective cohort study, Aged, Retrospective Studies, Pharmacology, aminoglycosides, Septic shock, business.industry, Retrospective cohort study, General Medicine, Middle Aged, medicine.disease, aminoglucósidos, efectividad-seguridad, Patient Discharge, Anti-Bacterial Agents, Cephalosporins, effectiveness-safety, Multiple drug resistance, Pseudomonas aeruginosa, Colistin, Ceftolozane, Female, business, medicine.drug
Abstract: RESUMEN Introducción Se necesitan datos comparativos en “vida real” sobre efectividad y seguridad de ceftolozano/tazobactam (C/T) frente otros regímenes (aminoglucósidos/colistina/combinación) en el tratamiento de Pseudomonas aeruginosa (PA) multirresistente (MDR) y extremadamente resistente (XDR) para establecer posicionamientos. Material y métodos Estudio observacional, retrospectivo de pacientes con confirmación microbiológica de PA MDR y XDR desde julio de 2016 a diciembre de 2018 en un hospital terciario. Variables: edad, sexo, comorbilidades, factores de riesgo de multirresistencia, variables relacionadas con infección, foco de infección, microorganismo y tipo de muestra, tratamiento antibiótico, curación clínica, curación microbiológica, recurrencia, mortalidad en ingreso y 30 días post-alta. Pacientes clasificados según tratamiento antibiótico recibido, C/T o aminoglucósidos/colistina/combinación. Resultados 405 pacientes con infección por PA MDR y XDR (73,1% hombres, edad media 63 ± 15 años). 87,1% PA XDR y 12,9% MDR. Todos los pacientes recibieron C/T como tratamiento dirigido y en el grupo aminoglucósidos/colistina/ combinación fueron el 73,5%. El grupo C/T presenta factores de peor pronóstico: shock séptico (30,0%) y sondaje (90,0%) (p
Published: 2021

37. Dystrophin Deficiency Causes Progressive Depletion of Cardiovascular Progenitor Cells in the Heart

Author: Alain Lacampagne, Petr Fojtík, Josef Jaroš, Pascal Amedro, Valérie Scheuermann, Marie Vincenti, Albano C. Meli, Vladimír Rotrekl, Franck Aimond, Petr Dvorak, Amanda Finan, Šárka Jelínková, Gilles Carnac, Gérald Hugon, Olivier Cazorla, Yvonne Sleiman, Deborah Beckerová, Sylvain Richard, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: 0301 basic medicine, Aging, mdx mouse, Duchenne muscular dystrophy, [SDV]Life Sciences [q-bio], Cardiomyopathy, 030204 cardiovascular system & hematology, Cardiovascular System, Dystrophin, Mice, 0302 clinical medicine, Myocytes, Cardiac, Biology (General), Spectroscopy, biology, Stem Cells, Cardiac muscle, Dilated cardiomyopathy, General Medicine, 3. Good health, Computer Science Applications, Chemistry, Proto-Oncogene Proteins c-kit, medicine.anatomical_structure, Cardiology, Cardiomyopathy, Dilated, musculoskeletal diseases, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, QH301-705.5, Article, Catalysis, Inorganic Chemistry, 03 medical and health sciences, Internal medicine, medicine, Animals, Humans, Physical and Theoretical Chemistry, QD1-999, Molecular Biology, duchenne muscular dystrophy, business.industry, Myocardium, Organic Chemistry, Skeletal muscle, genomic instability, medicine.disease, Muscular Dystrophy, Duchenne, dilated cardiomyopathy, Disease Models, Animal, 030104 developmental biology, Gene Expression Regulation, c-kit, Heart failure, Mice, Inbred mdx, biology.protein, cardiovascular progenitors, business, DNA Damage
Abstract: International audience; Duchenne muscular dystrophy (DMD) is a devastating condition shortening the lifespan of young men. DMD patients suffer from age-related dilated cardiomyopathy (DCM) that leads to heart failure. Several molecular mechanisms leading to cardiomyocyte death in DMD have been described. However, the pathological progression of DMD-associated DCM remains unclear. In skeletal muscle, a dramatic decrease in stem cells, so-called satellite cells, has been shown in DMD patients. Whether similar dysfunction occurs with cardiac muscle cardiovascular progenitor cells (CVPCs) in DMD remains to be explored. We hypothesized that the number of CVPCs decreases in the dystrophin-deficient heart with age and disease state, contributing to DCM progression. We used the dystrophin-deficient mouse model (mdx) to investigate age-dependent CVPC properties. Using quantitative PCR, flow cytometry, speckle tracking echocardiography, and immunofluorescence, we revealed that young mdx mice exhibit elevated CVPCs. We observed a rapid age-related CVPC depletion, coinciding with the progressive onset of cardiac dysfunction. Moreover, mdx CVPCs displayed increased DNA damage, suggesting impaired cardiac muscle homeostasis. Overall, our results identify the early recruitment of CVPCs in dystrophic hearts and their fast depletion with ageing. This latter depletion may participate in the fibrosis development and the acceleration onset of the cardiomyopathy.
Published: 2021

38. Obstetric and Perinatal Outcomes after Very Early Preterm Premature Rupture of Membranes (PPROM)-A Retrospective Analysis over the Period 2000–2020

Author: María José Benítez, Ernesto González-Mesa, Alberto Puertas-Prieto, Daniel Lubián-López, Juan Mozas-Moreno, Manuel Gómez-Castellanos, Osmayda Ulloa, Lorena Sabonet-Morente, Marta Blasco-Alonso, Jesús Jiménez-López, Cristina Gómez-Muñoz, Ernesto González-Cazorla, Materno-Infantil y Radiología, [González-Mesa,E, González-Cazorla,E] Surgical Specialities, Biochemistry and Inmunology Department, Malaga University, Málaga, Spain. [González-Mesa,E, Blasco-Alonso,M, Gómez-Muñoz,C, Sabonet-Morente,L, Gómez-Castellanos,M, Ulloa,O, Jiménez-López,J] Obstetrics and Gynecology Service, Regional University Hospital of Malaga, Málaga. [Benítez,MJ] Obstetrics and Gynecology Service, Virgen de la Victoria University Hospital, Málaga, Spain. [Puertas-Prieto,A, Mozas-Moreno,J] Obstetrics and Gynecology Service, Virgen de las Nieves University Hospital, Granada, Spain. [Mozas-Moreno,J] Department of Obstetrics and Gynecology, University of Granada, Granada, Spain. [Mozas-Moreno,J] Consortium for Biomedical Research in Epidemiology & Public Health (CIBER Epidemiología y Salud Pública-CIBERESP), Madrid, Spain. [Mozas-Moreno,J] Biohealth Research Institute (Instituto de Investigación Biosanitaria Ibs.GRANADA), Granada, Spain. [Lubián-López,D] Department of Obstetrics and Gynecology, University Hospital of Jerez de la Frontera, Faculty of Medicine, University of Cadiz, Cadiz, Spain., and This publication was financed with funds from the University of Malaga.
Subjects: Fetal Membranes, Premature Rupture, Medicine (General), Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies::Retrospective Studies [Medical Subject Headings], Edad gestacional, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Pregnancy, Retrospective analysis, 030212 general & internal medicine, Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Reproductive Physiological Processes::Reproduction::Pregnancy [Medical Subject Headings], Health Care::Health Care Facilities, Manpower, and Services::Health Facilities::Hospitals [Medical Subject Headings], Persons::Persons::Age Groups::Infant [Medical Subject Headings], 030219 obstetrics & reproductive medicine, Perinatal mortality, Obstetrics, Gestational age, Mortalidad perinatal, General Medicine, premature birth, Premature birth, perinatal mortality, Latency stage, Female, Rotura prematura de membranas fetales, medicine.medical_specialty, Anthropology, Education, Sociology and Social Phenomena::Education::Schools::Universities [Medical Subject Headings], Embarazo, Premature rupture of fetal membranes, Gestational Age, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Uncertainty [Medical Subject Headings], Article, Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Gestational Age [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Mortality::Perinatal Mortality [Medical Subject Headings], 03 medical and health sciences, R5-920, medicine, Humans, very early PPROM, Retrospective Studies, Fetus, business.industry, Infant, Newborn, Infant, Preterm Births, medicine.disease, Diseases::Female Urogenital Diseases and Pregnancy Complications::Pregnancy Complications::Obstetric Labor Complications::Fetal Membranes, Premature Rupture [Medical Subject Headings], Persons::Persons::Age Groups::Infant::Infant, Newborn [Medical Subject Headings], Check Tags::Female [Medical Subject Headings], Diseases::Female Urogenital Diseases and Pregnancy Complications::Pregnancy Complications::Obstetric Labor Complications::Obstetric Labor, Premature::Premature Birth [Medical Subject Headings], business, Premature rupture of membranes, Nacimiento prematuro
Abstract: Background and Objectives: Pre-term premature rupture of membranes (PPROM) responds for one third of preterm births, and it is associated with other complications that increase the risk of maternal or fetal poor outcome. To reduce uncertainty and provide accurate information to patients, the analysis of the large series is of great importance. In order to learn about the evolution over the time of the obstetric and perinatal outcomes in cases of PPROM at, or before, 28 weeks (very early PPROM) managed with an expectant/conservative protocol, we have designed the present study.&nbsp, Materials and Methods: We retrospectively studied all cases of very early PPROM attended in Malaga University Regional Hospital from 2000 to 2020. Results: Among 119888 deliveries assisted, 592 cases of PPROM occurred in pregnancies at or before 28 weeks (0.49% of all deliveries, 3.9% of all preterm births and 12.9% of all cases of PPROM). The mean duration of the latency period between PPROM and delivery was 13.5 days (range 0 to 88 days), enlarging over the years. The mean gestational age at delivery was 27 weeks (SD 2.9, range 17–34). The proportion of cesarean deliveries was 52.5%. The overall perinatal mortality rate was 26.5%, decreasing over the period with a significant correlation Pearson’s coefficient −0.128 (p &lt, 0.05). Conclusions: In the period 2000–2020, there was an improvement in the outcomes of very early PPROM cases and perinatal mortality showed a clear trend to decrease.
Published: 2021

39. Study of the Vaginal Microbiota in Healthy Women of Reproductive Age

Author: Eric Climent, Vicente Navarro-López, Melanie Cristine Alonzo Martínez, Empar Chenoll, Eduardo Cazorla, Esther Cánovas, and Juan F. Martinez-Blanch
Subjects: 0301 basic medicine, Microbiology (medical), QH301-705.5, 030106 microbiology, Population, Physiology, microbial communities, Luteal phase, Lactobacillus gasseri, Microbiology, Article, 03 medical and health sciences, Virology, Lactobacillus, medicine, Lactobacillus iners, Biology (General), education, Lactobacillus crispatus, vaginal microbiota, education.field_of_study, biology, Lactobacillus jensenii, dysbiosis, biology.organism_classification, medicine.disease, 030104 developmental biology, Dysbiosis, 16S Ribosomal RNA
Abstract: Understanding the characteristics of the vaginal microbiota of our patients allows us to carry out both a personalized therapeutic approach and a closer follow-up in those with microbiota susceptible to dysbiosis. This trial pursues the analysis of the vaginal microbiota of premenopausal women and its fluctuations within a four-week follow-up period. Vaginal samples of 76 fertile women were taken at a baseline visit and at a final visit (day 28 ± 5). To perform a phylogenetic study, we employed massive sequencing techniques to detect the 16S rRNA gene of the vaginal microbiota. The most prevalent vaginal microbial community was type I (34.87%), dominated by Lactobacillus crispatus. Vaginal microbial community types II (Lactobacillus gasseri) and V (Lactobacillus jensenii) were underrepresented in our population. When repeating the sampling process four weeks later, 75% of our patients maintained their initial bacterial community. In the follicular phase, the most recurrent microbiota was type III (Lactobacillus iners), in the periovulatory phase, types III and IV (microbial diversity), finally, in the luteal phase, the most frequent type was IV. The most prevalent vaginal bacterial community in our population was dominated by L. crispatus. The vaginal microbiota was resistant to changes in its bacterial community in 75% of our patients, even between consecutive menstrual cycles.
Published: 2021

40. Cataract in You-Hoover-Fong syndrome: TELO2 deficiency

Author: Angels García-Cazorla, Natalia Juliá-Palacios, Marta Morales-Ballús, Carla Veiga, Cristina Del-Prado-Sánchez, Judith Armstrong-Moron, and Stefano Grixolli-Mazzon
Subjects: Male, 0301 basic medicine, Microcephaly, Developmental Disabilities, Telomere-Binding Proteins, Mutation, Missense, Disease, 030105 genetics & heredity, Bioinformatics, Cataract, 03 medical and health sciences, 0302 clinical medicine, Intellectual Disability, medicine, Humans, Genetics (clinical), business.industry, Siblings, Infant, Telomere Homeostasis, medicine.disease, Ophthalmology, Child, Preschool, Pediatrics, Perinatology and Child Health, Global delay, 030221 ophthalmology & optometry, Female, Telomere maintenance 2, business, Pediatric cataract
Abstract: Recently, You, Hoover-Fong, and colleagues described a disease caused by a deficiency of the telomere maintenance 2 gene (We report two siblings, diagnosed with You-Hoover-Fong syndrome at the age of 28 and 14 months. Both were genetically studied to find the cause of their developmental delay and microcephaly.The identical compound heterozygous missense mutations in theWe report nuclear-lamellar cataracts in two siblings diagnosed with You-Hoover-Fong syndrome.
Published: 2020

41. Reporte de caso: Paciente Peruano de 52 años con Fibrosis Quística

Author: Franck De la Cruz, Ana Claudia Navarro-Solsol, Samuel Pecho-Silva, Omar Carrión, and Patrick Cazorla
Subjects: education.field_of_study, Pediatrics, medicine.medical_specialty, lcsh:R5-920, business.industry, Incidence (epidemiology), fibrosis quística en el adulto, lcsh:Public aspects of medicine, Population, lcsh:RA1-1270, General Medicine, Disease, medicine.disease, fibrosis quística, Cystic fibrosis, Medicine, business, education, lcsh:Medicine (General)
Abstract: La fibrosis quística (FQ) es una enfermedad genética autosómico y recesiva. Afecta con mucha más frecuencia a la población de origen caucásico, donde su incidencia varía de 1 entre 3 000 en caucásicos a 1 entre 8 000 en hispanos recién nacidos vivos. Para el 2018 se encontraban registrados 30 775 pacientes con fibrosis quística, de ellos menos del 10% de pacientes a nivel mundial tenían más de 40 años y ninguno había sido diagnosticado luego de los 40 años de edad. Presentamos a continuación el caso de un adulto peruano de 52 años con FQ. Este sería uno de los pacientes con el diagnóstico más tardío a nivel mundial y el paciente más longevo del Perú y uno de los más longevos de América Latina.
Published: 2020

42. Experience of using haemodialysis with medium cut-off dialyser in cast nephropathy

Author: Florentino Villanego Fernández, Javier Muñoz, Luis Alberto Vigara Sánchez, Juan Manuel Cazorla López, Ana Garcia Garcia-Doncel, and Manuel Ceballos Guerrero
Subjects: medicine.medical_specialty, Nephrology, business.industry, medicine, Urology, medicine.disease, business, lcsh:Diseases of the genitourinary system. Urology, lcsh:RC870-923, Nephropathy
Published: 2020

43. Poroqueratosis de Mibelli en la edad pediátrica

Author: Susana A Grees, María Belén Cazorla, Gisela Müller, Mónica Liliana Yarza, and Daniel Navacchia
Subjects: medicine.medical_specialty, Heterogeneous group, business.industry, Partial response, medicine, Topical treatment, Histopathological examination, medicine.disease, business, Dermatology, Porokeratosis, Cornoid lamella
Abstract: Las poroqueratosis son un grupo heterogéneo de trastornos de la queratinización epidérmica, de presentación infrecuente. Se caracterizan clínicamente por pápulas hiperqueratósicas que confluyen formando placas anulares con un centro atrófico y bordes sobreelevados. Hay seis variantes clínicas. El examen histopatológico evidencia la característica laminilla cornoide. Se presenta el caso de una niña de 2 años con diagnóstico de poroqueratosis de Mibelli y respuesta parcial al tratamiento tópico con tretinoínaal 0,025%, que actualmente continúa en seguimiento clínico.
Published: 2020

44. Poor sleep quality is associated with perinatal depression. A systematic review of last decade scientific literature and meta-analysis

Author: Ernesto González-Mesa, Beatriz Tripiana-Serrano, María Suárez-Arana, Ana Gonzalez-Cazorla, Nadia Ibrahim-Díez, Celia Cuenca-Marín, and Marta Blasco-Alonso
Subjects: Sleep Wake Disorders, medicine.medical_specialty, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, medicine, Humans, 030212 general & internal medicine, Psychiatry, Sleep disorder, Depression, business.industry, Obstetrics and Gynecology, Odds ratio, medicine.disease, Pregnancy Complications, Mood, Systematic review, Mood disorders, Meta-analysis, Pediatrics, Perinatology and Child Health, Anxiety, Female, medicine.symptom, business, 030217 neurology & neurosurgery, Perinatal Depression
Abstract: Background Although pregnancy is frequently associated with mental states of happiness, hope and well-being, some physical and psychological changes can contribute to increased sleep disturbances and worsened sleep quality. Sleep quality has been linked to negative emotions, anxiety and depression. The main objective of this paper was to systematically review the impact of sleep during pregnancy on maternal mood, studying the association between objective and subjective measures of sleep quality and perinatal depression. Methods We performed a systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, which included studies published between January 2008 and April 2019, and met the following criteria: (i) studies on pregnant women assessing the effects of sleep quality variables on perinatal mood disorders, (ii) studies published in English and (iii) full paper published in a peer-reviewed scientific journal with full-text format available. Results A total of 36 studies published in the last decade met the inclusion criteria for qualitative review and eight of them were suitable for meta-analysis. Both confirmed the negative effects of poor sleep on perinatal mood. However, qualitative analysis showed that unrepresentative samples and low participation rates falling below 80% biased some of the studies. The standard random-effects meta-analysis showed a pooled size effect [ln odds ratio (OR) 1.49 (95% confidence interval [CI] 1.19, 1.79)] for perinatal depression in cases of poor prenatal sleep quality, although heterogeneity was moderate to high [Q 16.05, P ≤ 0.025, H2 2.45 (95% CI 1.01, 13.70)]. Conclusion Poor sleep quality was associated with perinatal mood disturbances. The assessment of sleep quality along the pregnancy could be advisable with a view to offering preventative or therapeutic interventions when necessary.
Published: 2019

45. Clinical presentation and proteomic signature of patients with TANGO2 mutations

Author: Aurora Pujol, Sarah C. Grünert, Leigh B. Waddell, Cecilia Jimenez-Mallebrera, Ana Töpf, Frances J. Evesson, Antonia Ribes, Carlos Ortez, Daniel McArthur, Sandra T. Cooper, Charlotte L. Alston, Delia Yubero, Georgia Sarquella, Saikat Santra, Janbernd Kirschner, Agatha Schlüter, Rita Horvath, Kyle Thompson, Nicolai Kohlschmidt, Michael Champion, Hanns Lochmüller, Robert W. Taylor, Claudia Gross, Gina L. O’Grady, Maria del Mar O’Callaghan, Efsthatia Chronopoulou, M. A. Preece, Andrés Nascimento, Majumdar Anirban, Christian Turner, Denisa Hathazi, Germaine Pierre, Frederic Tort, Nadja Mingirulli, Raquel Montero, Sergei Korenev, Angela Pyle, Jennifer Duff, Andreas Roos, Angels García-Cazorla, Rafael Artuch, Plácido Navas, Cristina Jou, Horvath, Rita [0000-0002-9841-170X], Apollo - University of Cambridge Repository, Generalitat de Catalunya, Association Française contre les Myopathies, European Research Council, European Commission, Fundació La Marató de TV3, Instituto de Salud Carlos III, Medical Research Council (UK), National Institute for Health Research (UK), and Wellcome Trust
Subjects: metabolic encephalomyopathy, Male, Proteomics, Mitochondrial Diseases, Fisiologia patològica, Respiratory chain, Medizin, Golgi Apparatus, TANGO2, Oxidative Phosphorylation, Rhabdomyolysis, fatty acid metabolism, Cognitive decline, Pathological physiology, health care economics and organizations, Genetics (clinical), chemistry.chemical_classification, 0303 health sciences, Muscle Weakness, Brain Diseases, Metabolic, 030305 genetics & heredity, Metabolic disorder, Fatty Acids, Homozygote, Errors congènits del metabolisme, proteomic analysis, 3. Good health, medicine.anatomical_structure, Phenotype, Lactic acidosis, Original Article, Female, education, Oxidative phosphorylation, Inborn errors of metabolism, Biology, 03 medical and health sciences, mitochondrial dysfunction, Genetics, medicine, Humans, rhabdomyolysis, 030304 developmental biology, Whole Genome Sequencing, Skeletal muscle, Infant, Original Articles, medicine.disease, Molecular biology, Enzyme, Membrane protein, chemistry, Mutation
Abstract: Transport And Golgi Organization protein 2 (TANGO2) deficiency has recently been identified as a rare metabolic disorder with a distinct clinical and biochemical phenotype of recurrent metabolic crises, hypoglycemia, lactic acidosis, rhabdomyolysis, arrhythmias, and encephalopathy with cognitive decline. We report nine subjects from seven independent families, and we studied muscle histology, respiratory chain enzyme activities in skeletal muscle and proteomic signature of fibroblasts. All nine subjects carried autosomal recessive TANGO2 mutations. Two carried the reported deletion of exons 3 to 9, one homozygous, one heterozygous with a 22q11.21 microdeletion inherited in trans. The other subjects carried three novel homozygous (c.262C>T/p.Arg88*; c.220A>C/p.Thr74Pro; c.380+1G>A), and two further novel heterozygous (c.6_9del/p.Phe6del); c.11‐13delTCT/p.Phe5del mutations. Immunoblot analysis detected a significant decrease of TANGO2 protein. Muscle histology showed mild variation of fiber diameter, no ragged‐red/cytochrome c oxidase‐negative fibers and a defect of multiple respiratory chain enzymes and coenzyme Q10 (CoQ10) in two cases, suggesting a possible secondary defect of oxidative phosphorylation. Proteomic analysis in fibroblasts revealed significant changes in components of the mitochondrial fatty acid oxidation, plasma membrane, endoplasmic reticulum‐Golgi network and secretory pathways. Clinical presentation of TANGO2 mutations is homogeneous and clinically recognizable. The hemizygous mutations in two patients suggest that some mutations leading to allele loss are difficult to detect. A combined defect of the respiratory chain enzymes and CoQ10 with altered levels of several membrane proteins provides molecular insights into the underlying pathophysiology and may guide rational new therapeutic interventions., Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR), Grant/Award Number: 2014: SGR 393; Association Française contre les Myopathies (FR), Grant/Award Number: 21644; CERCA Programme/ Generalitat de Catalunya, the Hesperia Foundation, the Secretariat for Universities and Research of the Ministry of Business and Knowledge of the Government of Catalonia, Grant/Award Number: [2017SGR1206]; European Research Council, Grant/Award Number: 309548; FEuropean Union Seventh Framework Programme, Grant/Award Number: (FP7/2007‐2013); Instituto de la Marató de TV3, Grant/Award Number: 345/C/2014rm Care (CA); Instituto de Salud Carlos III, Grant/Award Number: grants PI17‐01286, PI17/00109, PI16/00579, PI16/01048, PI14/00581 and CP09/00011; Medical Research Council, Grant/Award Number: MR/N025431/1; Mitochondrial Disease Patient Cohort (UK) , Grant/Award Number: (G0800674); National Institute for Health Research (NIHR) doctoral fellowship, Grant/Award Number: NIHR‐HCS‐D12‐03‐04; Newton Fund, Grant/Award Number: MR/N027302/1; Wellcome Centre for Mitochondrial Research, Grant/Award Number: (203105/Z/16/Z); Wellcome Investigator fund, Grant/Award Number: 109915/Z/15/Z; Wellcome Trust Pathfinder Scheme, Grant/Award Number: 201064/Z/16/Z
Published: 2019

46. The most recurrent monogenic disorders that overlap with the phenotype of Rett syndrome

Author: S. Vidal, N. Brandi, P. Pacheco, J. Maynou, G. Fernandez, C. Xiol, A. Pascual-Alonso, M. Pineda, J. Armstrong, O'Callaghan Maria del Mar, Àngels Garcia-Cazorla, Maria del Carmen Serrano Munuera, Silvia Cuso García, Monica Troncoso, Guillermo Fariña, Juan José García Peñas, Belen Gil Fournier, Soraya Ramiro León, Miriam Guitart, Neus Baena, Guiomar Perez de Nanclares, Intzane Ocio Oci, Eva Gutiérrez-Delicado, Belén Abarrategui, Eva Barroso, Fernando Santos-Simarro, Pablo Lapunzina, Francisco J. García, Juan M. Acedo, Asunción García, Miguel A. Martinez, and Antonio Martínez-Bermejo
Subjects: congenital, hereditary, and neonatal diseases and abnormalities, Adolescent, Methyl-CpG-Binding Protein 2, CDKL5, Rett syndrome, Genotype-phenotype correlations, SYNGAP1, Bioinformatics, RTT, Rett-like, MECP2, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Neurodevelopmental disorder, 030225 pediatrics, Rett Syndrome, medicine, Humans, STXBP1, Genetic Association Studies, Monogenic disorders, business.industry, High-Throughput Nucleotide Sequencing, General Medicine, medicine.disease, Phenotype, FOXG1, Neurodevelopmental Disorders, Mutation, Pediatrics, Perinatology and Child Health, Female, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Rett syndrome (RTT) is an early-onset neurodevelopmental disorder that is caused by mutations in the MECP2 gene; however, defects in other genes (CDKL5 and FOXG1) can lead to presentations that resemble classic RTT, although they are not completely identical. Here, we attempted to identify other monogenic disorders that share features of RTT. A total of 437 patients with a clinical diagnosis of RTT-like were studied; in 242 patients, a custom panel with 17 genes related to an RTT-like phenotype was run via a HaloPlex-Target-Enrichment-System. In the remaining 195 patients, a commercial TruSight-One-Sequencing-Panel was analysed. A total of 40 patients with clinical features of RTT had variants which affect gene function in six genes associated with other monogenic disorders. Twelve patients had variants in STXBP1, nine in TCF4, six in SCN2A, five in KCNQ2, four in MEF2C and four in SYNGAP1. Genetic studies using next generation sequencing (NGS) allowed us to study a larger number of genes associated with RTT-like simultaneously, providing a genetic diagnosis for a wider group of patients. These new findings provide the clinician with more information and clues that could help in the prevention of future symptoms or in pharmacologic therapy.
Published: 2019

47. Effect of brivaracetam on the anger levels of epilepsy patients. A prospective open-labelled controlled study

Author: Gonzalo Mazuela, Manuel Toledo, Laura Abraira, Manuel Quintana, Sonia Cazorla, and Estevo Santamarina
Subjects: Adult, Male, medicine.medical_specialty, media_common.quotation_subject, Comorbidity, Anger, Brivaracetam, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, Quality of life, Internal medicine, mental disorders, medicine, Humans, In patient, Prospective Studies, Adverse effect, media_common, Psychiatric Status Rating Scales, business.industry, Mental Disorders, General Medicine, Middle Aged, medicine.disease, Pyrrolidinones, Treatment Outcome, Mood, Neurology, Quality of Life, Anticonvulsants, Female, Neurology (clinical), Levetiracetam, business, 030217 neurology & neurosurgery, Follow-Up Studies, medicine.drug
Abstract: Purpose The rate of brivaracetam-related behavioural adverse events is a current focus of discussion. This study aims to assess the effect of brivaracetam on anger levels in patients with epilepsy, adjusted by mood symptoms, history of psychiatric disorders and seizure response. Method Prospective analysis of 37 patients assessed for anger levels (STAXI-2), depression-anxiety (HADS) and quality of life (QOLIE-10) before adjunctive brivaracetam treatment and reassessed 3–6 months later. A control group following the same protocol of assessment was used for 1:1 comparison. A high percentage of mood stabilisers were included in this control group. Results Brivaracetam was indicated for patients including focal onset (79%) and generalised epilepsies (21%). Nearly 60% of responders and no psychiatric adverse events were found. This was similar to controls. The overall results revealed that brivaracetam was assoiciated with better in anger levels, mood scores and quality of life at baseline. Prior use of levetiracetam or the presence of a psychiatric background did not influence the results. However, improvements in anger levels were seen in the brivaracetam responders. Conclusion This study shows that brivaracetam is not associated with an increased level of anger in patients with either focal or generalised epilepsies in the absence of psychiatric comorbidity. However, an improvement in anger levels is possibly influenced by a good seizure response.
Published: 2019

48. Seasonal analysis of the atmosphere during five years by using microwave radiometry over a mid-latitude site

Author: Carlos D. Hoyos, Roberto Román, Pablo Ortiz-Amezcua, Alberto Cazorla, I. Foyo-Moreno, Gregori de Arruda Moreira, Juan Luis Guerrero-Rascado, Lucas Alados-Arboledas, Francisco Navas-Guzmán, Elena Montilla-Rosero, Jose Antonio Benavent-Oltra, Francisco José Olmo-Reyes, and Andrés Esteban Bedoya-Velásquez
Subjects: Atmospheric Science, 010504 meteorology & atmospheric sciences, Planetary boundary layer, Microwave radiometer, 010501 environmental sciences, Seasonality, Atmospheric sciences, Atmospheric temperature, medicine.disease, temperature and relative humidity, 01 natural sciences, law.invention, Troposphere, Atmosphere, microwave radiometer, 13. Climate action, law, medicine, Radiosonde, integrated water vapor (IWV), Environmental science, Relative humidity, 0105 earth and related environmental sciences
Abstract: This work focuses on the analysis of the seasonal cycle of temperature and relative humidity (RH) profiles and integrated water vapor (IWV) obtained from microwave radiometer (MWR) measurements over the mid-latitude city of Granada, southern Spain. For completeness the study, the maximum atmospheric boundary layer height (ABLHmax) is also included. To this end, we have firstly characterized the HATPRO-RPG MWR errors using 55 co-located radiosondes (RS) by means of the mean-bias (biasbar) profile and the standard deviation (SDbias) profile classified under all-weather conditions and cloud-free conditions. This characterization pointed out that temperature from HATPRO-MWR presents a very low biasbar respects RS mostly below 2.0 km agl, ranging from positive to negative values under all-weather conditions (from 1.7 to -0.4 K with SDbias up to 3.0 K). Under cloud-free conditions, the bias was very similar to that found under all-weather conditions (1.8 to -0.4 K) but with smaller SDbias (up to 1.1 K). The same behavior is also seen in this lower part (ground to 2.0 km agl) for RH. Under all-weather conditions, the mean RH bias ranged from 3.0 to -4.0% with SDbias between 10 and 16.3% while under cloud-free conditions the bias ranged from 2.0 to -0.4% with SDbias from 0.5 to 13.3%. Above 2.0 km agl, the SDbias error increases considerably up to 4 km agl (up to -20%), and then decreases slightly above 7.0 km agl (up to -5%). In addition, IWV values from MWR were also compared with the values obtained from the integration of RS profiles, showing a better linear fit under cloud-free conditions (R2 = 0.96) than under all-weather conditions (R2 = 0.82). The mean bias under cloud-free conditions was -0.80 kg/m2 while for all-weather conditions it was -1.25 kg/m2. Thus, the SDbiasfor all the statistics (temperature, RH and IWV) of the comparison between MWR and RS presented higher values for all-weather conditions than for cloud-free conditions ones. It points out that the presence of clouds is a key factor to take into account when MWR products are used. The second part of this work is devoted to a seasonal variability analysis over five years, leading us to characterize thermodynamically the troposphere over our site. This city atmosphere presents a clear seasonal cycle where temperature, ABLHmax and IWV increase from winter to summer and decrease in autumn, meanwhile RH decreases along the warmer seasons. This city presents cold winters (mean daily maximum temperature: 10.6 ± 1.1 °C) and dry/hot summers (mean daily maximum temperature of 28.8 ± 0.9 °C and mean daily maximum of surface RH up to 55.0 ± 6.0%) at surface (680 m asl). Moreover, considering temporal trends, our study pointed out that only temperature and RH showed a linear increase in winters with a mean-rate of (0.5 ± 0.1) °C/year and (3.4 ± 1.7) %/year, respectively, from ground to 2.0 km agl, meanwhile IWV presented a linear increase of 1.0 kg·m-2/year in winters, 0.78 kg·m-2/year in summers and a linear decrease in autumns of -0.75 kg·m-2/year., Andalusia Regional Government through project P12-RNM-2409, Spanish Ministry of Economy and Competitiveness through projects CGL2013-45410-R, CGL2015-73250-JIN and CGL2016-81092-R, Juan de la Cierva grant IJCI-2016-30007
Published: 2019

49. Betaine anhydrous in homocystinuria: results from the RoCH registry

Author: Yann Nadjar, Luis Aldámiz-Echevarría, Vassili Valayannopoulos, Vincent Rigalleau, María L. Couce, Pascal Cathebras, Dries Dobbelaere, Aline Cano, Nathalie Guffon, Lena Damaj, Manuel Schiff, Angeles Garcia-Cazorla, Virginie Levrat, Didier Eyer, Mercedes Martinez-Pardo Casanova, François Maillot, Guy Touati, Dominique Brunet, Luis Peña-Quintana, Jaime Dalmau, Sylvie Hieronimus, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Robert Debré, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Maladies RAres du DEveloppement embryonnaire et du MEtabolisme : du Phénotype au Génotype et à la Fonction - ULR 7364 (RADEME), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), and Université Francois Rabelais [Tours]
Subjects: 0301 basic medicine, Male, lcsh:Medicine, 030105 genetics & heredity, chemistry.chemical_compound, 0302 clinical medicine, Betaine, Pharmacology (medical), Registries, RoCH registry, Child, Homocysteine, Genetics (clinical), biology, Interstitial lung disease, General Medicine, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 3. Good health, Treatment Outcome, Child, Preschool, Population study, Female, Homocystinuria, France, Safety, Adult, medicine.medical_specialty, Adolescent, Efficacy, Cobalamin, 03 medical and health sciences, Young Adult, Betaine anhydrous, Efficacy, Homocystinuria, RoCH registry, Safety, Internal medicine, medicine, Humans, Adverse effect, Retrospective Studies, business.industry, Research, lcsh:R, Infant, Betaine anhydrous, medicine.disease, Cystathionine beta synthase, chemistry, Spain, Methylenetetrahydrofolate reductase, biology.protein, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, 030217 neurology & neurosurgery
Abstract: Background The Registry of Adult and Paediatric Patients Treated with Cystadane® – Homocystinuria (RoCH) is a non-interventional, observational, multi-centre, post-authorization safety study that aimed to identify safety of betaine anhydrous (Cystadane®) in the treatment of patients with inborn errors of homocysteine metabolism (homocystinuria) in order to minimise the treatment associated risks and establish better knowledge on its clinical use. The registry included patients of all ages with homocystinuria who were treated with betaine anhydrous in conjunction with other therapies. Clinical data were collected retrospectively from 2007 to 2013, then prospectively up to February 2014. All adverse events (AEs) reported during the study were recorded. The clinical and biological status of patients was monitored at least once a year. Results A total of 125 patients with homocystinuria (adults [> 18 years]: 50; paediatric [≤18 years]: 75) were enrolled at 29 centres in France and Spain. Patients were treated with betaine anhydrous for a mean duration of 7.4 ± 4.3 years. The median total daily dose of betaine anhydrous at the first and last study visits was 6 g/day for cystathionine β-synthase (CBS)-deficient vitamin B6 responders and 9 g/day for methylenetetrahydrofolate reductase-deficient patients, while the median daily dose increased in CBS-deficient B6 non-responders (from 6 to 9 g/day) and cobalamin metabolism-defective patients (from 3 to 6 g/day) between the first and last visits. Treatment caused a mean overall reduction of 29% in plasma homocysteine levels in the study population. A total of 277 AEs were reported during the study, of which two non-serious AEs (bad taste and headache) and one serious AE (interstitial lung disease) were considered to be drug related. Overall, betaine anhydrous was well tolerated with no major safety concerns. Conclusions Data from the RoCH registry provided real-world evidence on the clinical safety and efficacy of betaine anhydrous in the management of homocystinuria in paediatric and adult patients. Electronic supplementary material The online version of this article (10.1186/s13023-019-1036-2) contains supplementary material, which is available to authorized users.
Published: 2019

50. AA amyloidosis of unknown origin in New-Caledonia with focus on the association with gout: a consecutive case series of 20 patients

Author: Nicolas Quirin, Jean-Simon Rech, David Buob, Gilles Grateau, Sophie Georgin-Lavialle, and Cecile Cazorla
Subjects: Serum Amyloid A Protein, medicine.medical_specialty, Gout, Intravenous drug, business.industry, Amyloidosis, Consecutive case series, medicine.disease, Dermatology, AA amyloidosis, Internal Medicine, Humans, Medicine, business
Abstract: In the past decades, main causes of AA amyloidosis were inflammatory rheumatic or bowel diseases, neoplasia and chronic infections. Now a days, autoinflammatory-diseases and intravenous drug inject...
Published: 2021

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