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202. Early management of acutely ill ward patients.

Author

Frost, Paul J. and Wise, Matt P.

Subjects
*EARLY medical intervention, *ACUTE diseases, *MEDICAL needs assessment, *MEDICAL quality control, *PHYSICIANS, *GRADUATES, *PREVENTION, *DIAGNOSIS
Abstract

The article discusses the recommendations given by different organizations to form a step-wise approach that may be used by junior doctors for an early and effective management of patients suffering from acute illness. The steps involved in the approach include immediate assessment, assessment of airway, assessment of breathing and circulation and diagnostic synthesis and definitive management. Several case scenarios are presented to highlight the challenges and the way they can be overcome. INSETS: CASE SCENARIO: PART 1;CASE SCENARIO: PART 2.

Published
2012
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203. A Clinical Case of COVID-19-Associated Pulmonary Aspergillosis (CAPA), Illustrating the Challenges in Diagnosis (Despite Overwhelming Mycological Evidence).

Author

White, P. Lewis, Springer, Jan, Wise, Matt P., Einsele, Hermann, Löffler, Claudia, Seif, Michelle, Prommersberger, Sabrina, Backx, Matthijs, and Löffler, Jürgen

Subjects
PULMONARY aspergillosis, COVID-19, DIAGNOSTIC imaging, ALGORITHMS, MYCOLOGY
Abstract

The COVID-19 pandemic has resulted in large numbers of patients requiring critical care management. With the established association between severe respiratory virus infection and invasive pulmonary aspergillosis (7.6% for COVID-19-associated pulmonary aspergillosis (CAPA)), the pandemic places a significant number of patients at potential risk from secondary invasive fungal disease. We described a case of CAPA with substantial supporting mycological evidence, highlighting the need to employ strategic diagnostic algorithms and weighted definitions to improve the accuracy in diagnosing CAPA. [ABSTRACT FROM AUTHOR]

Published
2022
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204. Associations between enteral nutrition and outcomes in the SUP‐ICU trial: Results of exploratory post hoc analyses.

Author

Borthwick, Mark, Granholm, Anders, Marker, Søren, Krag, Mette, Lange, Theis, Wise, Matt P., Bendel, Stepani, Keus, Frederik, Guttormsen, Anne Berit, Schefold, Joerg C., Wetterslev, Jørn, Perner, Anders, and Møller, Morten Hylander

Subjects
*ENTERAL feeding, *PNEUMONIA-related mortality, *PROTON pump inhibitors, *INTENSIVE care units, *GASTROINTESTINAL hemorrhage
Abstract

Background: Enteral nutrition may affect risks of gastrointestinal bleeding, pneumonia and mortality in critically ill patients and may also modify the effects of pharmacological stress ulcer prophylaxis. We undertook post hoc analyses of the stress ulcer prophylaxis in the intensive care unit trial to assess for any associations and interactions between enteral nutrition and pantoprazole. Methods: Extended Cox models with time‐varying co‐variates and competing events were used to assess potential associations, adjusted for baseline severity of illness. Potential interactions between daily enteral nutrition and allocation to pantoprazole on outcomes were similarly assessed. Results: Enteral nutrition was associated with lower risk of clinically important gastrointestinal bleeding (cause‐specific hazard ratio [HR]: 0.29, 95% confidence interval: [CI] 0.19–0.44, p <.001), higher risk of pneumonia (HR: 1.44, 95% CI: 1.14–1.82, p =.003), and lower risk of all‐cause mortality (HR: 0.22, 95% CI: 0.18–0.27, p <.001). Enteral nutrition with allocation to pantoprazole was associated with a lower risk of mortality (HR: 0.27, 95% CI: 0.21–0.35, p <.001), similar to enteral nutrition with allocation to placebo (HR: 0.17, 95% CI: 0.13–0.23, p <.001). Allocation to pantoprazole with no enteral nutrition had little effect on mortality (HR: 0.83, 95% CI: 0.63–1.09, p =.179), whilst allocation to pantoprazole and receipt of enteral nutrition was mostly compatible with increased all‐cause mortality (HR: 1.27, 95% CI: 0.99–1.64, p =.061). The test of interaction between enteral nutrition and pantoprazole treatment allocation for all‐cause mortality was statistically significant (p =.024). Conclusions: Enteral nutrition was associated with an increased risk of pneumonia and a reduced risk of gastrointestinal bleeding. The interaction between pantoprazole and enteral nutrition suggesting an increased risk of mortality requires further study. [ABSTRACT FROM AUTHOR]

Published
2024
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205. The Oral Cavity, Biofilms and Ventilator-Associated Pneumonia

Author

W. Williams, David, A.O. Lewis, Michael, J. Marino, Paola, and P. Wise, Matt

Abstract

Ventilator-associated pneumonia (VAP) is the most prevalent infection in intensive care units (ICUs) and second only to urinary tract sepsis amongst hospital-acquired infections. The endotracheal tube is an important component in the pathogenesis of VAP, as it both subverts the normal defence mechanisms of the respiratory tract and offers a surface that can support biofilm growth, thereby providing a reservoir of potential respiratory pathogens. Traditionally recognized VAP pathogens include Staphylococcus aureus and Gram-negative bacteria such as Pseudomonas aeruginosa and members of the Enterobacteriaceae family. These microorganisms are not recognized as members of the normal oral microflora, but are thought to infect the lungs endogenously via the oropharyngeal route. Prior to entering the lower respiratory tract, there is evidence that the oral cavity does become colonised by respiratory pathogens. In this regard, it is probable that the normal oral microflora is an influencing factor for VAP, either through affecting recruitment of respiratory pathogens to oral plaque, or to biofilms that develop in the endotracheal tube. Indeed the ability of several Streptococcus species belonging to the normal oral microflora to promote recruitment of bacteria to plaque biofilm through production of extracellular glucans has long been recognised. Recent studies have indeed highlighted that poor oral hygiene is a risk factor for VAP and therefore the maintenance of adequate oral health care in ventilated patients represents an important preventative strategy.

Published
2012

206. Lung Defence Mechanisms and Their Potential Role in the Prevention of Ventilator Associated Pneumonia

Author

Wise, Matt, Lightowler, Josephine, and Garrard, Christopher

Abstract

Ventilator associated pneumonia remains a cause of significant morbidity and mortality in Intensive Care patients despite advances in knowledge and technology. The presence of an endotracheal tube bypassing the normal airway barriers, oropharyngeal bacterial colonisation, patient position and repetitive micro-aspiration tip the host-pathogen relationship in favour of the pathogen and promote lung infection in a time-dependent manner. Defending the lung against microbial invasion and infection is a multiplicity of innate and adaptive immune mechanisms, which can identify and eliminate potential pathogens. These defence mechanisms include the ability to recognise pathogens through cell-surface receptors, antimicrobial peptides and proteins, pro and anti-inflammatory mediators and factors related to the coagulant state of the lung fluid. The mechanisms are characterised by their complexity, their remarkable degree of redundancy and effectiveness.

Published
2006

207. High-frequency oscillatory ventilation and acute respiratory distress syndrome: at the crossroads?

Author

Wise, Matt P., Saayman, Anton G., and Gillies, Michael A.

Subjects
*ADULT respiratory distress syndrome treatment, *PATIENT management, *HIGH-frequency ventilation (Therapy), *LUNG disease treatment, *SEDATIVES -- Overdose, *PREVENTION
Abstract

The author discusses the importance of conventional lung protective ventilation in managing patients with acute respiratory distress syndrome (ARDS). He states that the suggested optimal protective strategy of using high-frequency oscillatory ventilation (HFOV) for the treatment of ARDS did not proven to be beneficial. He suggests avoiding overdistension of lung, judicious use of fluids, and sedatives for managing patients that can only be achieved through experience of using HFOV.

Published
2013
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209. Should selective digestive decontamination be used in critically ill patients?

Author

Walden, Andrew P., Bonten, Marc J., and Wise, Matt P.

Subjects
CHLORHEXIDINE, CRITICAL care medicine, DRUG resistance in microorganisms, THERAPEUTICS
Abstract

The article discusses whether selective digestive decontamination could be used in critically ill patients. Selective digestive decontamination involves the administration of topical antibiotics to the oropharynx and stomach in combination with parenteral antimicrobials to reduce infection in the aerodigestive tract. Although there is increasing evidence suggesting usefulness of this method, clinicians remain skeptical. It is suggested that this method seems to be beneficial for reducing healthcare associated infection in critically ill patients where low levels of antibiotic resistant bacteria exist. Decontamination of the oropharynx with antiseptics such as chlorhexidine seems to offer a safe and effective alternative across a variety of healthcare systems.

Published
2012
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210. CD4 T cells can reject major histocompatibility complex class I-incompatible skin grafts

Author

Wise, Matt, Zelenika, Diana, Bemelman, Frederike, Latinne, Dominique, Bazin, Hervé, Cobbold, Stephen, and Waldmann, Herman

Abstract

We have re-investigated the roles of CD4 and CD8 T cell subsets in skin graft rejection across a single class I MHC disparity. Recipient mice were transplanted with skin from donors transgenic for the class I MHC molecule Kb. As expected, CD8 T cells were sufficient for rapid injection; but surprisingly, CD4 T cells were also competent to do the same. Rejection was dependent on one or the other subset, since elimination of both resulted in indefinite graft survival. The possibility that alloantibody was the downstream effector of CD4 mediated rejection was excluded because CD8-depleted mice rendered B cell deficient still rejected rapidly, but T cell-depleted recipients with pre-existing high titers of alloantibody were unable to do so. In addition, if CD4 cells act to reject by recruiting and/or activating macrophages then this was not dependent on CR3, IFN-γ or TNF-α. Transplantation of skin grafts where the MHC class I disparity was at the level of passenger leukocytes only, demonstrated that transient bystander damage could occur, but that this was insufficient to result in full rejection. We surmise that for CD4 T cells to reject an MHC class I-incompatible graft it is necessary that an appropriate allogeneic peptide is processed and presented in the context of recipient MHC class II. CD4 T cells from B6 mice may fail to reject skin from MHC class I mutants because of the lack of such MHC class II-restricted presentation.

Published
1999
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212. Additional file 6 of Predicting neurological outcome after out-of-hospital cardiac arrest with cumulative information; development and internal validation of an artificial neural network algorithm

Author

Andersson, Peder, Johnsson, Jesper, Björnsson, Ola, Cronberg, Tobias, Hassager, Christian, Zetterberg, Henrik, Stammet, Pascal, Undén, Johan, Kjaergaard, Jesper, Friberg, Hans, Blennow, Kaj, Lilja, Gisela, Wise, Matt P., Dankiewicz, Josef, Nielsen, Niklas, and Frigyesi, Attila

Subjects
health care facilities, manpower, and services, 3. Good health
Abstract

Additional file 6: Table 1D. Day 3–72 hours of ICU treatment.

213. Additional file 4 of Predicting neurological outcome after out-of-hospital cardiac arrest with cumulative information; development and internal validation of an artificial neural network algorithm

Author

Andersson, Peder, Johnsson, Jesper, Björnsson, Ola, Cronberg, Tobias, Hassager, Christian, Zetterberg, Henrik, Stammet, Pascal, Undén, Johan, Kjaergaard, Jesper, Friberg, Hans, Blennow, Kaj, Lilja, Gisela, Wise, Matt P., Dankiewicz, Josef, Nielsen, Niklas, and Frigyesi, Attila

Subjects
health care facilities, manpower, and services, 3. Good health
Abstract

Additional file 4: Table 1B. Day 1–24 hours of ICU treatment.

214. Additional file 6 of Predicting neurological outcome after out-of-hospital cardiac arrest with cumulative information; development and internal validation of an artificial neural network algorithm

Author

Andersson, Peder, Johnsson, Jesper, Björnsson, Ola, Cronberg, Tobias, Hassager, Christian, Zetterberg, Henrik, Stammet, Pascal, Undén, Johan, Kjaergaard, Jesper, Friberg, Hans, Blennow, Kaj, Lilja, Gisela, Wise, Matt P., Dankiewicz, Josef, Nielsen, Niklas, and Frigyesi, Attila

Subjects
health care facilities, manpower, and services, 3. Good health
Abstract

Additional file 6: Table 1D. Day 3–72 hours of ICU treatment.

215. Additional file 5 of Predicting neurological outcome after out-of-hospital cardiac arrest with cumulative information; development and internal validation of an artificial neural network algorithm

Author

Andersson, Peder, Johnsson, Jesper, Björnsson, Ola, Cronberg, Tobias, Hassager, Christian, Zetterberg, Henrik, Stammet, Pascal, Undén, Johan, Kjaergaard, Jesper, Friberg, Hans, Blennow, Kaj, Lilja, Gisela, Wise, Matt P., Dankiewicz, Josef, Nielsen, Niklas, and Frigyesi, Attila

Subjects
health care facilities, manpower, and services, 3. Good health
Abstract

Additional file 5: Table 1C. Day 2–48 hours of ICU treatment.

216. Long-term mortality in the European, randomised SUP-ICU trial

Author

Søren Marker, Mette Krag, Anders Perner, Jørn Wetterslev, Theis Lange, Wise, Matt P., Mark Borthwick, Stepani Bendel, Frederik Keus, Anne Berit Guttormsen, Schefold, Joerg C., Rasmussen, Bodil S., Thomas Elkmann, Morten Bestle, Bjørn Arenkiel, Laake, Jon H., Kamper, Maj K., Maarit Lang, Pawlowicz-Dworzanska, Malgorzata B., Sari Karlsson, Janne Liisanantti, Nilanjan Dey, Heidi Knudsen, Anders Granholm, and Morten Hylander Møller

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217. Additional file 5 of Predicting neurological outcome after out-of-hospital cardiac arrest with cumulative information; development and internal validation of an artificial neural network algorithm

Author

Andersson, Peder, Johnsson, Jesper, Björnsson, Ola, Cronberg, Tobias, Hassager, Christian, Zetterberg, Henrik, Stammet, Pascal, Undén, Johan, Kjaergaard, Jesper, Friberg, Hans, Blennow, Kaj, Lilja, Gisela, Wise, Matt P., Dankiewicz, Josef, Nielsen, Niklas, and Frigyesi, Attila

Subjects
health care facilities, manpower, and services, 3. Good health
Abstract

Additional file 5: Table 1C. Day 2–48 hours of ICU treatment.

218. Additional file 4 of Predicting neurological outcome after out-of-hospital cardiac arrest with cumulative information; development and internal validation of an artificial neural network algorithm

Author

Andersson, Peder, Johnsson, Jesper, Björnsson, Ola, Cronberg, Tobias, Hassager, Christian, Zetterberg, Henrik, Stammet, Pascal, Undén, Johan, Kjaergaard, Jesper, Friberg, Hans, Blennow, Kaj, Lilja, Gisela, Wise, Matt P., Dankiewicz, Josef, Nielsen, Niklas, and Frigyesi, Attila

Subjects
health care facilities, manpower, and services, 3. Good health
Abstract

Additional file 4: Table 1B. Day 1–24 hours of ICU treatment.

219. Carbon dioxide dynamics in relation to neurological outcome in resuscitated out-of-hospital cardiac arrest patients: an exploratory Target Temperature Management Trial substudy.

Author

Ebner, Florian, Harmon, Matt B. A., Aneman, Anders, Cronberg, Tobias, Friberg, Hans, Hassager, Christian, Juffermans, Nicole, Kjærgaard, Jesper, Kuiper, Michael, Mattsson, Niklas, Pelosi, Paolo, Ullén, Susann, Undén, Johan, Wise, Matt P., Nielsen, Niklas, Kjærgaard, Jesper, Ullén, Susann, and Undén, Johan

Abstract

Background: Dyscarbia is common in out-of-hospital cardiac arrest (OHCA) patients and its association to neurological outcome is undetermined.Methods: This is an exploratory post-hoc substudy of the Target Temperature Management (TTM) trial, including resuscitated OHCA patients, investigating the association between serial measurements of arterial partial carbon dioxide pressure (PaCO2) and neurological outcome at 6 months, defined by the Cerebral Performance Category (CPC) scale, dichotomized to good outcome (CPC 1 and 2) and poor outcome (CPC 3-5). The effects of hypercapnia and hypocapnia, and the time-weighted mean PaCO2 and absolute PaCO2 difference were analyzed. Additionally, the association between mild hypercapnia (6.0-7.30 kPa) and neurological outcome, its interaction with target temperature (33 °C and 36 °C), and the association between PaCO2 and peak serum-Tau were evaluated.Results: Of the 939 patients in the TTM trial, 869 were eligible for analysis. Ninety-six percent of patients were exposed to hypocapnia or hypercapnia. None of the analyses indicated a statistical significant association between PaCO2 and neurological outcome (P = 0.13-0.96). Mild hypercapnia was not associated with neurological outcome (P = 0.78) and there was no statistically significant interaction with target temperature (Pinteraction = 0.95). There was no association between PaCO2 and peak serum-Tau levels 48 or 72 h after return of spontaneous circulation (ROSC).Conclusions: Dyscarbia is common after ROSC. No statistically significant association between PaCO2 in the post-cardiac arrest phase and neurological outcome at 6 months after cardiac arrest was detected. There was no significant interaction between mild hypercapnia and temperature in relation to neurological outcome. [ABSTRACT FROM AUTHOR]

Published
2018
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223. The importance of diagnostic testing in the management of community-acquired respiratory infection during influenza season.

Author

Holmes, Tom W . L., Campbell, Andrew, Sinha, Jaisi, and Wise, Matt P.

Subjects
LETTERS to the editor, INFLUENZA diagnosis
Abstract

A letter to the editor is presented in response to the article "When should a diagnosis of influenza be considered in adults requiring intensive care unit admission? Results from population-based active surveillance in Toronto," S. Kuster and colleagues in a 2011 issue.

Published
2012
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224. Does the evidence support the use of mild hypothermia after cardiac arrest? NO.

Author

Walden, Andrew P., Nielsen, Niklas, and Wise, Matt P.

Subjects
MYOCARDIAL infarction treatment, INDUCED hypothermia
Abstract

The article presents the authors' insights regarding the findings of several guidelines which advise the use of hypothermia for comatose patients after cardiac arrest. It questions the validity and sufficiency of evidence from clinical trials because the optimal temperature of hypothermia utilization after cardiac arrest is still unknown. It concludes that further data from well designed studies are needed to determine temperature control.

Published
2011

225. Method of Height Determination Used in Predicted Body Weight Equations.

Author

Hingston, Christopher D., Morgan, Matt P., Wise, Matt P., and Smith, Ann

Subjects
BODY weight, ANTHROPOMETRY, RESPIRATORY insufficiency treatment, ALGORITHMS, ARTIFICIAL respiration
Abstract

A letter to the editor in response to the article "Method of Height Determination Used in Predicted Body Weight Equations," that was published in a previous issue of the journal is presented.

Published
2016
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226. Coffee brewing technique as a confounder in observational studies.

Author

Hingston, Christopher D. and Wise, Matt P.

Subjects
*COFFEE, *CORONARY disease, *CALCINOSIS
Abstract

A letter to the editor is presented in response to the article "Coffee consumption and coronary artery calcium in young and middle-aged asymptomatic adults" by researcher Y. Choi and colleagues published in the previous issue of the journal.

Published
2015
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229. Editorial from Guest Editors [Hot Topic: Pulmonary Infections in Critical Care (Guest Editors: Matt P. Wise and Anton G. Saayman)]

Author

P. Wise, Matt and G. Saayman, Anton

Abstract

This issue of Current Respiratory Medicine Reviews is dedicated to pulmonary infections in critical care and an ensemble of international experts have been brought together to review this important subject. Meeting new challenges in the management of pulmonary infections in the critically ill requires a greater understanding of pulmonary defence mechanisms, pathogenesis and diagnosis of infection, so that new strategies can be employed whilst at the same time making better use of currently available drugs. Nationwide trends demonstrate that an ever-increasing number of patients are being admitted to hospital with sepsis syndromes. Although absolute numbers of patients dying from sepsis are rising, this has been tempered by a reduction in mortality rates [1-3]. An ageing population with comorbid disease, more frequent use of indwelling medical devices and immunosuppression all contribute to the observation of an increase in sepsis. In the SOAP study, which examined sepsis in 198 European intensive care units, the most frequent site of infection was the lung and was present in two thirds of patients on arrival to critical care [4]. Community-acquired pneumonia remains an important reason for admission to both hospital and critical care and continues to rise, partly in response to an ageing population [5-7]. An additional burden on critical care capacity is posed by healthcare-associated pneumonia (HCAP), hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP) which are frequently caused by organisms with bacterial resistance to multiple antibiotics and consequently higher treatment failure rates are often observed. Emergence of multidrug resistant organisms amongst community-acquired infections is a further area of concern [8]. New and emerging infections, which are often first identified in critically ill patients, pose an additional encumbrance [9, 10]. Erosion of the antimicrobial armamentarium is unfortunately set against a backdrop of a limited pipeline of new antimicrobial drugs coming into clinical practice. Wilkinson and colleagues review the complexity of pulmonary defence mechanisms that repel respiratory pathogens continually accessing the airway. They explore how an understanding of host immunity can improve vaccination strategies and lead to novel therapies. Williams et al. discuss the importance of the oral cavity in the pathogenesis of VAP and how an understanding of biofilm biology is fundamental to both the aetiology of VAP and developing new preventative therapies. Young and Doyle examine the central role of the endotracheal tube in VAP and how improvements in tube design may prevent its occurrence. Diagnosing VAP remains a challenge for the physician and the inability to accurately identify patients with VAP has undoubtedly hampered research in this area [11]. In their review Grover and colleagues discuss how established and novel biomarkers might enhance diagnostic certainty. Clinicians frequently focus on bacterial infections in the critically ill but are now realising that other organisms pose an increasing burden particularly in those with prolonged periods of ventilation. Linssen et al. discuss the impact of latent viral infections in mechanically ventilated patients, whilst Barnes reviews pulmonary fungal infections, which are often difficult to both diagnose and treat. The first influenza pandemic in over 40 years was caused by a novel influenza A strain, A(H1N1)pdm09 and this had a huge impact on critical care across the globe, including the postpandemic period. Dunning and Openshaw describe the clinical features of this disease and the treatment options available. Iannella and Luna consider the impact and aetiology of treatment failure in VAP including host, bacterial, and therapeutic factors. Complementary to this Dhanani and colleagues review how antibiotics may be optimally used including alternate modes of administration, continuous infusions, therapeutic drug monitoring and combination therapy. Poulakou et al. examine the burden and treatment options for Methicillin-resistant Staphylococcus aureus (MRSA), which is no longer limited to being a nosocomial pathogen. Notwithstanding the armamentarium available to physicians in modern healthcare systems, pulmonary infections will continue to present a challenge for critical care physicians and patients alike....

Published
2012

232. Associations between enteral nutrition and outcomes in the SUP‐ICU trial: Protocol for exploratory post hoc analyses.

Author

Borthwick, Mark, Granholm, Anders, Marker, Søren, Krag, Mette, Lange, Theis, Wise, Matt P., Bendel, Stepani, Keus, Frederik, Guttormsen, Anne Berit, Schefold, Joerg C., Wetterslev, Jørn, Perner, Anders, and Møller, Morten Hylander

Subjects
*ENTERAL feeding, *GASTROINTESTINAL hemorrhage
Abstract

Critically ill patients are at risk of gastrointestinal (GI) bleeding. Counter measures to minimise this risk include the use of pharmacological stress ulcer prophylaxis (SUP). The effect of enteral nutrition as SUP on GI bleeding event rates is unknown. There are conflicting data describing the effect of co‐administration of enteral nutrition with pharmacological SUP, and there is substantial variation in practice. We aim to conduct an exploratory post hoc analysis to evaluate the association of enteral nutrition with clinically important GI bleed rates in ICU patients included in the SUP‐ICU trial, and to explore any interactions between enteral nutrition and pharmacologic SUP on patient outcomes. The SUP‐ICU trial dataset will be used to assess if enteral nutrition is associated with the outcomes of interest. Extended Cox models will be used considering relevant competing events, including treatment allocation (SUP or placebo) and enteral nutrition as a daily time‐varying covariate, with additional adjustment for severity of illness (SAPS II). Results will be presented as adjusted hazard ratios for treatment allocation and enteral nutrition, and for treatment allocation and enteral nutrition considering potential interactions with the other variable, all with 95% confidence intervals and p‐values for the tests of interaction. All results will be considered as exploratory only. This post hoc analysis may yield important insights to guide practice and inform the design of future randomised clinical trial investigating the effect of enteral nutrition on GI bleeding. [ABSTRACT FROM AUTHOR]

Published
2023
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234. Steroid-induced hyperglycaemia and pulmonary disease.

Author

Wise, Matt P., Brooks, Anthony P., and Purcell-Jones, Megan H.

Subjects
*HYPERGLYCEMIA, *OBSTRUCTIVE lung diseases, *ADRENOCORTICAL hormones, *STEROIDS, *THERAPEUTICS
Abstract

The article provides information on a study which showed that hyperglycaemia could be used as a predictor of outcome during non-invasive ventilation in decompensated chronic obstructive pulmonary disease (COPD). It offers information on airway surface fluid as a key element of pulmonary defense and on corticosteroids as a treatment modality in pulmonary and extrapulmonary diseases. Further study on the phenomenon, not only for COPD but for other pulmonary diseases in which steroids are used, is recommended.

Published
2011
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235. Consider time of presentation.

Author

Frost, Paul and Wise, Matt P.

Subjects
*LETTERS to the editor, *BRAIN injuries
Abstract

A letter to the editor is presented in response to the article "Predicting Outcome After Traumatic Brain Injury: Practical Prognostic Models Based on Large Cohort of International Patients" in the February 23, 2008 issue.

Published
2008
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239. Interleukin-6 as a prognostic biomarker of clinical outcomes after traumatic brain injury: a systematic review.

Author

Ooi, Setthasorn Zhi Yang, Spencer, Robert James, Hodgson, Megan, Mehta, Samay, Phillips, Nicholas Lloyd, Preest, Gwilym, Manivannan, Susruta, Wise, Matt P, Galea, James, and Zaben, Malik

Subjects
*BRAIN injuries, *INTERLEUKIN-6, *CEREBROSPINAL fluid, *TREATMENT effectiveness, *BIOMARKERS
Abstract

Traumatic brain injury (TBI) is a major cause of mortality and morbidity worldwide. There are currently no early biomarkers for prognosis in routine clinical use. Interleukin-6 (IL-6) is a potential biomarker in the context of the established role of neuroinflammation in TBI recovery. Therefore, a systematic review of the literature was performed to assess and summarise the evidence for IL-6 secretion representing a useful biomarker for clinical outcomes. A multi-database literature search between January 1946 and July 2021 was performed. Studies were included if they reported adult TBI patients with IL-6 concentration in serum, cerebrospinal fluid (CSF) and/or brain parenchyma analysed with respect to functional outcome and/or mortality. A synthesis without meta-analysis is reported. Fifteen studies were included, reporting 699 patients. Most patients were male (71.7%), and the pooled mean age was 40.8 years; 78.1% sustained severe TBI. Eleven studies reported IL-6 levels in serum, six in CSF and one in the parenchyma. Five studies on serum demonstrated higher IL-6 concentrations were associated with poorer outcomes, and five showed no signification association. In CSF studies, one found higher IL-6 levels were associated with poorer outcomes, one found them to predict better outcomes and three found no association. Greater parenchymal IL-6 was associated with better outcomes. Despite some inconsistency in findings, it appears that exaggerated IL-6 secretion predicts poor outcomes after TBI. Future efforts require standardisation of IL-6 measurement practices as well as assessment of the importance of IL-6 concentration dynamics with respect to clinical outcomes, ideally within large prospective studies. Prospero registration number: CRD42021271200 [ABSTRACT FROM AUTHOR]

Published
2022
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240. Mechanically Ventilated Patients Shed High-Titer Live Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) for Extended Periods From Both the Upper and Lower Respiratory Tract.

Author

Saud, Zack, Ponsford, Mark, Bentley, Kirsten, Cole, Jade M, Pandey, Manish, Jolles, Stephen, Fegan, Chris, Humphreys, Ian, Wise, Matt P, and Stanton, Richard

Subjects
*PREVENTION of infectious disease transmission, *SALIVA microbiology, *INTENSIVE care units, *COVID-19, *ACADEMIC medical centers, *VIRAL load, *ARTIFICIAL respiration, *POLYMERASE chain reaction, *LONGITUDINAL method
Abstract

Background SARS-CoV-2 infection can lead to severe acute respiratory distress syndrome needing intensive care admission and may lead to death. As a virus that transmits by respiratory droplets and aerosols, determining the duration of viable virus shedding from the respiratory tract is critical for patient prognosis, and informs infection-control measures both within healthcare settings and the public domain. Methods We prospectively examined upper and lower airway respiratory secretions for both viral RNA and infectious virions in mechanically ventilated patients admitted to the intensive care unit (ICU) of the University Hospital of Wales. Samples were taken from the oral cavity (saliva), oropharynx (subglottic aspirate), or lower respiratory tract (nondirected bronchoalveolar lavage [NBAL] or bronchoalveolar lavage [BAL]) and analyzed by both quantitative PCR (qPCR) and plaque assay. Results 117 samples were obtained from 25 patients. qPCR showed extremely high rates of positivity across all sample types; however, live virus was far more common in saliva (68%) than in BAL/NBAL (32%). Average titers of live virus were higher in subglottic aspirates (4.5 × 107) than in saliva (2.2 × 106) or BAL/NBAL (8.5 × 106) and reached >108 PFU/mL in some samples. The longest duration of shedding was 98 days, while most patients (14/25) shed live virus for ≥20 days. Conclusions ICU patients infected with SARS-CoV-2 can shed high titers of virus both in the upper and lower respiratory tract and tend to be prolonged shedders. This information is important for decision making around cohorting patients, de-escalation of personal protective equipment, and undertaking potential aerosol-generating procedures. [ABSTRACT FROM AUTHOR]

Published
2022
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241. Caregiver burden and health-related quality of life amongst caregivers of out-of-hospital cardiac arrest survivors.

Author

Bohm, Mattias, Cronberg, Tobias, Årestedt, Kristofer, Friberg, Hans, Hassager, Christian, Kjaergaard, Jesper, Kuiper, Michael, Nielsen, Niklas, Ullén, Susann, Undén, Johan, Wise, Matt P., and Lilja, Gisela

Subjects
*BURDEN of care, *CAREGIVERS, *CARDIAC arrest, *QUALITY of life, *ST elevation myocardial infarction
Abstract

Aims: To describe burden and health-related quality of life amongst caregivers of out-of-hospital cardiac arrest survivors and explore the potential association with cognitive function of the survivors. Caregivers of patients with ST-elevation myocardial infarction were used as controls.Methods: Data were collected from the cognitive substudy of the Targeted Temperature Management-trial. Caregiver burden was assessed with the 22-item Zarit Burden Interview, with scores ≤20 considered as no burden. Health-related quality of life was assessed with the SF-36v2®, with T-scores 47-53 representing the norm. Cardiac arrest survivors were categorized based on the results from cognitive assessments as having "no cognitive impairment" or "cognitive impairment".Results: Follow-up 6 months post event was performed for caregivers of 272 cardiac arrest survivors and 108 matched myocardial infarction controls, included at an intended ratio of 2:1. In general, caregivers of cardiac arrest survivors and controls reported similar caregiver burden. The overall scores for quality of life were within normative levels and similar for caregivers of cardiac arrest survivors and control patients. Compared to those with no cognitive impairment, caregivers of cognitively impaired cardiac arrest survivors (n = 126) reported higher levels of burden (median 18 versus 8, p < 0.001) and worse quality of life in five of eight domains, particularly "Role-Emotional" (mean 45.7 versus 49.5, p = 0.002).Conclusions: In general, caregivers of cardiac arrest survivors and myocardial infarction controls reported similar levels of burden and quality of life. Cognitive outcome and functional dependency of the cardiac arrest survivor impact burden and quality of life of the caregiver. [ABSTRACT FROM AUTHOR]

Published
2021
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242. Serum markers of brain injury can predict good neurological outcome after out-of-hospital cardiac arrest.

Author

Moseby-Knappe, Marion, Mattsson-Carlgren, Niklas, Stammet, Pascal, Backman, Sofia, Blennow, Kaj, Dankiewicz, Josef, Friberg, Hans, Hassager, Christian, Horn, Janneke, Kjaergaard, Jesper, Lilja, Gisela, Rylander, Christian, Ullén, Susann, Undén, Johan, Westhall, Erik, Wise, Matt P., Zetterberg, Henrik, Nielsen, Niklas, and Cronberg, Tobias

Subjects
*GLIAL fibrillary acidic protein, *CARDIAC arrest, *BRAIN injuries, *DEUBIQUITINATING enzymes, *TAU proteins, *FRONTOTEMPORAL lobar degeneration, *COMA
Abstract

Purpose: The majority of unconscious patients after cardiac arrest (CA) do not fulfill guideline criteria for a likely poor outcome, their prognosis is considered "indeterminate". We compared brain injury markers in blood for prediction of good outcome and for identifying false positive predictions of poor outcome as recommended by guidelines. Methods: Retrospective analysis of prospectively collected serum samples at 24, 48 and 72 h post arrest within the Target Temperature Management after out-of-hospital cardiac arrest (TTM)-trial. Clinically available markers neuron-specific enolase (NSE) and S100B, and novel markers neurofilament light chain (NFL), total tau, ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) were analysed. Normal levels with a priori cutoffs specified by reference laboratories or defined from literature were used to predict good outcome (no to moderate disability, Cerebral Performance Category scale 1–2) at 6 months. Results: Seven hundred and seventeen patients were included. Normal NFL, tau and GFAP had the highest sensitivities (97.2–98% of poor outcome patients had abnormal serum levels) and NPV (normal levels predicted good outcome in 87–95% of patients). Normal S100B and NSE predicted good outcome with NPV 76–82.2%. Normal NSE correctly identified 67/190 (35.3%) patients with good outcome among those classified as "indeterminate outcome" by guidelines. Five patients with single pathological prognostic findings despite normal biomarkers had good outcome. Conclusion: Low levels of brain injury markers in blood are associated with good neurological outcome after CA. Incorporating biomarkers into neuroprognostication may help prevent premature withdrawal of life-sustaining therapy. [ABSTRACT FROM AUTHOR]

Published
2021
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244. Serum GFAP and UCH-L1 for the prediction of neurological outcome in comatose cardiac arrest patients.

Author

Ebner, Florian, Moseby-Knappe, Marion, Mattsson-Carlgren, Niklas, Lilja, Gisela, Dragancea, Irina, Undén, Johan, Friberg, Hans, Erlinge, David, Kjaergaard, Jesper, Hassager, Christian, Wise, Matt P., Kuiper, Michael, Stammet, Pascal, Wanscher, Michael, Horn, Janneke, Ullén, Susann, Cronberg, Tobias, and Nielsen, Niklas

Subjects
*CARDIAC arrest, *GLIAL fibrillary acidic protein, *CARDIAC patients, *VENTRICULAR fibrillation, *FORECASTING, *SERUM
Abstract

Objective: Neurological outcome prediction is crucial early after cardiac arrest. Serum biomarkers released from brain cells after hypoxic-ischaemic injury may aid in outcome prediction. The only serum biomarker presently recommended in the European Resuscitation Council prognostication guidelines is neuron-specific enolase (NSE), but NSE has limitations. In this study, we therefore analyzed the outcome predictive accuracy of the serum biomarkers glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1) in patients after cardiac arrest.Methods: Serum GFAP and UCH-L1 were collected at 24, 48 and 72 h after cardiac arrest. The primary outcome was neurological function at 6-month follow-up assessed by the cerebral performance category scale (CPC), dichotomized into good (CPC1-2) and poor (CPC3-5). Prognostic accuracies were tested with receiver-operating characteristics by calculating the area under the receiver-operating curve (AUROC) and compared to the AUROC of NSE.Results: 717 patients were included in the study. GFAP and UCH-L1 discriminated between good and poor neurological outcome at all time-points when used alone (AUROC GFAP 0.88-0.89; UCH-L1 0.85-0.87) or in combination (AUROC 0.90-0.91). The combined model was superior to GFAP and UCH-L1 separately and NSE (AUROC 0.75-0.85) at all time-points. At specificities ≥95%, the combined model predicted poor outcome with a higher sensitivity than NSE at 24 h and with similar sensitivities at 48 and 72 h.Conclusion: GFAP and UCH-L1 predicted poor neurological outcome with high accuracy. Their combination may be of special interest for early prognostication after cardiac arrest where it performed significantly better than the currently recommended biomarker NSE. [ABSTRACT FROM AUTHOR]

Published
2020
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245. Pantoprazole prophylaxis in ICU patients with high severity of disease: a post hoc analysis of the placebo-controlled SUP-ICU trial.

Author

Marker, Søren, Perner, Anders, Wetterslev, Jørn, Krag, Mette, Lange, Theis, Wise, Matt P., Borthwick, Mark, Bendel, Stepani, Keus, Frederik, Guttormsen, Anne Berit, Schefold, Joerg C., Møller, Morten Hylander, and SUP-ICU investigators

Subjects
*PANTOPRAZOLE, *INTENSIVE care units, *PREVENTIVE medicine, *APACHE (Disease classification system), *CATASTROPHIC illness, *CLASSIFICATION, *MORTALITY, *PATIENTS, *PLACEBOS, *PREVENTIVE health services, *RANDOMIZED controlled trials, *TREATMENT effectiveness
Abstract

Purpose: In the subgroup of patients with Simplified Acute Physiology Score (SAPS) II > 53 in the Stress Ulcer Prophylaxis in Intensive Care Unit (SUP-ICU) trial, there was interaction (P = 0.049) suggesting increased mortality in patients allocated to pantoprazole as compared with placebo. We aimed to explore this further.Methods: The SUP-ICU trial allocated acutely admitted adults at risk of gastrointestinal bleeding to pantoprazole vs placebo. In this post hoc study, we repeated all the preplanned analyses of SUP-ICU in patients with baseline SAPS II > 53.Results: A total of 1140 patients had a complete SAPS II > 53 and were included. At 90 days, 272/579 patients (47%) assigned to pantoprazole had died, as compared with 229/558 patients (41%) assigned to placebo [relative risk 1.13; 95% confidence interval (CI) 1.00-1.29]. This was supported by sensitivity analyses adjusted for risk factors and those in the per-protocol population. When accounting for patients with incomplete SAPS II in two additional analyses, the relative risk was 1.08; 95% CI 0.96-1.22 and 1.10; 95% CI 0.97-1.25. This was also observed for the secondary outcome days alive without life support. There were no differences between the intervention groups in the other secondary outcomes.Conclusions: In this post hoc analysis of patients with high disease severity included in the SUP-ICU trial, we observed higher 90-day mortality and fewer days alive without life support with pantoprazole vs placebo. Some of this may have been explained by missing SAPS II data, but further research is needed to draw firm conclusions. CLINICALTRIALS.GOV: ClinicalTrials.gov No. NCT02467621. [ABSTRACT FROM AUTHOR]

Published
2019
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246. Detailed analysis of health-related quality of life after out-of-hospital cardiac arrest.

Author

Bohm, Mattias, Lilja, Gisela, Finnbogadóttir, Hafrún, Cronberg, Tobias, Undén, Johan, Friberg, Hans, Kjærgaard, Jesper, Nielsen, Niklas, Wise, Matt P., and Åkerman, Eva

Subjects
*QUALITY of life, *CARDIAC arrest, *CHI-squared test, *LONGITUDINAL method, *QUESTIONNAIRES, *AGE distribution, *MENTAL health, *SEX distribution, *SURVEYS, *WORLD health, *ACTIVITIES of daily living
Abstract

Aim: To describe the detailed health-related quality of life (HRQoL) in survivors from the TTM-trial and to investigate potential differences related to sex and age.Methods: This is a cross-sectional study originating from a large prospective international, multicentre trial, including 442 respondents who answered the Short Form-36 item Questionnaire Health Survey version 2® (SF-36v2®) at a structured follow-up 6 months after out-of-hospital cardiac arrest (OHCA). Statistical analysis between independent groups were performed with Mann-Whitney U or Chi-square. Age was analysed primarily as a dichotomised variable.Results: Although overall physical and mental health were within the normal range, a substantial proportion of respondents had impaired function at domain-specific levels, particularly in Role-Physical (50%) and Role-Emotional (35%). Females scored significantly lower than males in; Physical Functioning (41.7 vs. 47.9, p < 0.001), Role-Physical (40.4 vs. 44.3, p = 0.02), General Health (47.0 vs. 50.5, p = 0.02), Vitality (47.2 vs. 52.7, p < 0.001), and Role-Emotional (41.5 vs. 46.2, p = 0.009). Those ≤65 years scored significantly better in Physical Functioning (47.9 vs. 44.1 p < 0.001), while those >65 years scored significantly better in Vitality (50.8 vs. 53.7, p = 0.006) and Mental Health (50.3 vs. 52.6, p = 0.04).Conclusions: Many OHCA survivors demonstrated impaired function in HRQoL at a domain level, despite most patients reporting an acceptable general HRQoL. Females reported worse HRQoL than males. Older age was associated with a worse Physical Functioning but better Vitality and Mental Health. Role-Physical and Role-Emotional aspects of health were especially affected, even when effects of age and sex where accounted for. [ABSTRACT FROM AUTHOR]

Published
2019
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247. Comparison of four clinical risk scores in comatose patients after out-of-hospital cardiac arrest.

Author

Schmidbauer, Simon, Rylander, Christian, Cariou, Alain, Wise, Matt P., Thomas, Matthew, Keeble, Thomas R., Erlinge, David, Haenggi, Matthias, Wendel-Garcia, Pedro D., Bělohlávek, Jan, Grejs, Anders Morten, Nielsen, Niklas, Friberg, Hans, and Dankiewicz, Josef

Subjects
*DISEASE risk factors, *CARDIAC arrest, *MISSING data (Statistics), *MEDICAL needs assessment, *CLINICAL medicine
Abstract

Several different scoring systems for early risk stratification after out-of-hospital cardiac arrest have been developed, but few have been validated in large datasets. The aim of the present study was to compare the well-validated Out-of-hospital Cardiac Arrest (OHCA) and Cardiac Arrest Hospital Prognosis (CAHP)-scores to the less complex MIRACLE2- and Target Temperature Management (TTM)-scores. This was a post-hoc analysis of the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial. Missing data were handled by multiple imputation. The primary outcome was discriminatory performance assessed as the area under the receiver operating characteristics-curve (AUROC), with the outcome of interest being poor functional outcome or death (modified Rankin Scale 4–6) at 6 months after OHCA. Data on functional outcome at 6 months were available for 1829 cases, which constituted the study population. The pooled AUROC for the MIRACLE2-score was 0.810 (95% CI 0.790–0.828), 0.835 (95% CI 0.816–0.852) for the TTM-score, 0.820 (95% CI 0.800–0.839) for the CAHP-score and 0.770 (95% CI 0.748–0.791) for the OHCA-score. At the cut-offs needed to achieve specificities >95%, sensitivities were <40% for all four scoring systems. The TTM-, MIRACLE2- and CAHP-scores are all capable of providing objective risk estimates accurate enough to be used as part of a holistic patient assessment after OHCA of a suspected cardiac origin. Due to its simplicity, the MIRACLE2-score could be a practical solution for both clinical application and risk stratification within trials. [ABSTRACT FROM AUTHOR]

Published
2023
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248. Brain injury markers in blood predict signs of hypoxic ischaemic encephalopathy on head computed tomography after cardiac arrest.

Author

Lagebrant, Alice, Lang, Margareta, Nielsen, Niklas, Blennow, Kaj, Dankiewicz, Josef, Friberg, Hans, Hassager, Christian, Horn, Janneke, Kjaergaard, Jesper, Kuiper, Mikael A., Mattsson-Carlgren, Niklas, Pellis, Tommaso, Rylander, Christian, Sigmund, Roger, Stammet, Pascal, Undén, Johan, Zetterberg, Henrik, Wise, Matt P., Cronberg, Tobias, and Moseby-Knappe, Marion

Subjects
*CARDIAC arrest, *GLIAL fibrillary acidic protein, *BRAIN injuries, *ASPHYXIA neonatorum, *NEUROLOGIC examination, *BRAIN diseases
Abstract

Signs of hypoxic ischaemic encephalopathy (HIE) on head computed tomography (CT) predicts poor neurological outcome after cardiac arrest. We explore whether levels of brain injury markers in blood could predict the likelihood of HIE on CT. Retrospective analysis of CT performed at 24–168 h post cardiac arrest on clinical indication within the Target Temperature Management after out-of-hospital cardiac arrest-trial. Biomarkers prospectively collected at 24- and 48 h post-arrest were analysed for neuron specific enolase (NSE), neurofilament light (NFL), total-tau and glial fibrillary acidic protein (GFAP). HIE was assessed through visual evaluation and quantitative grey-white-matter ratio (GWR) was retrospectively calculated on Swedish subjects with original images available. In total, 95 patients were included. The performance to predict HIE on CT (performed at IQR 73–116 h) at 48 h was similar for all biomarkers, assessed as area under the receiving operating characteristic curve (AUC) NSE 0.82 (0.71–0.94), NFL 0.79 (0.67–0.91), total-tau 0.84 (0.74–0.95), GFAP 0.79 (0.67–0.90). The predictive performance of biomarker levels at 24 h was AUC 0.72–0.81. At 48 h biomarker levels below Youden Index accurately excluded HIE in 77.3–91.7% (negative predictive value) and levels above Youden Index correctly predicted HIE in 73.3–83.7% (positive predictive value). NSE cut-off at 48 h was 48 ng/ml. Elevated biomarker levels irrespective of timepoint significantly correlated with lower GWR. Biomarker levels can assess the likelihood of a patient presenting with HIE on CT and could be used to select suitable patients for CT-examination during neurological prognostication in unconscious cardiac arrest patients. [ABSTRACT FROM AUTHOR]

Published
2023
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249. 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. 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, 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. R., George, F. G., Aguirre, J. S., Buensuseso, J. A., Bruns, M. M., Schouten, J. A., Van Wezel, H. M., Heines, S. J., Buise, M. P., Goodson, J. C., Browne, T. S., Hutchison, R. A., Bailey, M. B., Hacking, D. J., Andersen, F. H., Dolva, M. S., 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., 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., Estilita, J. M., Barros, F. M., Serra, I. M., Martinho, A. M., Tomescu, D. R., Bedreag, O. H., Corneci, D. E., Negoita, S. L., Gritsan, A. I., Gazenkampf, A. A., Albarrak, M. M., Mustafa, G. M., Maghrabi, K. A., Aisa, T. M., Jabbary, A. S. A., Arabi, Y. M., Trinidad, O. A., Dorzi, H. M. A., Tabhan, E. E., Lopez-Delgado, J. C., Albaiceta, G. 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. L., Morin, A. -K., Zender, H. O., Souissi, A. B., Girgin, N. K., Unal, N., Meco, B. C., Akyol, O. O., Derman, S. S., Mcauley, D., Humphreys, S. K., Raj, A. S., Fawkes, D. A., Thomas, R. R. J. M., Smith, M. J., Hormis, A. P., Kannan, S. G., O'Neill, O., Scott, C. J., Ellis, H. E., Mckechnie, S., Hutton, P. J., Ditomasso, N. N., Vitale, M. N., Griffin, R. O., Dean, M. N., Cranshaw, J. H., Willett, E. L., Preez, P. D., Williams, A. J., Degordoa, L. O. -R., Chau, S. K., Mccalman, K. H., Allan, R. 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., O'Kane, S. C., Frigyik, A. D., Careless, J. P., May, M. M., Trinder, T. J., Hagan, S. J., Wise, M. P., Cole, J. M., Macfie, C. C., Dowling, A. T., Nunez, E., Imperio, M. C., Franca, A. G., Banner-Goodspeed, V. M., Beitler, J. R., Mukkera, S. R., Shinn, J. O., Yeatts, D. 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., 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

250. Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest.

Author

Nielsen, Niklas, Wetterslev, Jørn, Cronberg, Tobias, Erlinge, David, Gasche, Yvan, Hassager, Christian, Horn, Janneke, Hovdenes, Jan, Kjaergaard, Jesper, Kuiper, Michael, Pellis, Tommaso, Stammet, Pascal, Wanscher, Michael, Wise, Matt P., Åneman, Anders, Al-Subaie, Nawaf, Boesgaard, Søren, Bro-Jeppesen, John, Brunetti, Iole, and Bugge, Jan Frederik

Subjects
*BODY temperature, *BODY temperature regulation, *CARDIAC arrest, *CLINICAL trials, *HEALTH outcome assessment, *PATIENTS
Abstract

The article discusses research which investigated benefits and dangers associated with two targeted temperature regimens for preventing fever in cardiac arrest patients. It reports recruitment and screening of patients for the randomized clinical trial, intervention assignments performed, and details of the trial protocol established. It also offers details relating to patient outcomes recorded, statistical analysis done, and results of life-sustaining therapy withdrawal.

Published
2013
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