2015 Dec 1 - Characteristics and Outcomes of Eligible Nonenrolled Patients in a Mechanical Ventilation Trial of Acute Respiratory Distress Syndrome

Yaseen M. Arabi, Deborah J. Cook, Qi Zhou, Orla Smith, Lori Hand, Alexis F. Turgeon, Andrea Matte, Sangeeta Mehta, Russell Graham, Kristin Brierley, Neill K. J. Adhikari, Maureen O. Meade, and Niall D. Ferguson  Am. J. Resp. Crit. Care Med. Dec 1, 2015, vol. 192, no. 11: 1306-1313

Rationale: Patients eligible for randomized controlled trials may not be enrolled for various reasons. Nonenrollment may affect study generalizability and lengthen the time required for trial completion.

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2015 Dec 1 - A Multicenter Randomized Trial of Continuous versus Intermittent β-Lactam Infusion in Severe Sepsis

Joel M. Dulhunty, Jason A. Roberts, Joshua S. Davis, Steven A. R. Webb, Rinaldo Bellomo, Charles Gomersall, Charudatt Shirwadkar, Glenn M. Eastwood, John Myburgh, David L. Paterson, Therese Starr, Sanjoy K. Paul, and Jeffrey Lipman  Am. J. Resp. Crit. Care Med. Dec 1, 2015, vol. 192, no. 11: 1298-1305

Rationale: Continuous infusion of β-lactam antibiotics may improve outcomes because of time-dependent antibacterial activity compared with intermittent dosing.

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2015 Nov 15 - Early High-Volume Hemofiltration versus Standard Care for Post–Cardiac Surgery Shock. The HEROICS Study

Alain Combes, Nicolas Bréchot, Julien Amour, Nathalie Cozic, Guillaume Lebreton, Catherine Guidon, Elie Zogheib, Jean-Claude Thiranos, Jean-Christophe Rigal, Olivier Bastien, Hamina Benhaoua, Bernard Abry, Alexandre Ouattara, Jean-Louis Trouillet, Alain Mallet, Jean Chastre, Pascal Leprince, and Charles-Edouard Luyt  Am. J. Resp. Crit. Care Med. Nov 15, 2015, vol. 192, no. 10: 1179-1190

Rationale: Post–cardiac surgery shock is associated with high morbidity and mortality. By removing toxins and proinflammatory mediators and correcting metabolic acidosis, high-volume hemofiltration (HVHF) might halt the vicious circle leading to death by improving myocardial performance and reducing vasopressor dependence.

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2015 Nov 1 - Evolution of Diaphragm Thickness during Mechanical Ventilation. Impact of Inspiratory Effort

Ewan C. Goligher, Eddy Fan, Margaret S. Herridge, Alistair Murray, Stefannie Vorona, Debbie Brace, Nuttapol Rittayamai, Ashley Lanys, George Tomlinson, Jeffrey M. Singh, Steffen-Sebastian Bolz, Gordon D. Rubenfeld, Brian P. Kavanagh, Laurent J. Brochard, and Niall D. Ferguson  Am. J. Resp. Crit. Care Med. Nov 1, 2015, vol 192, no, 9: 1080-1088

Rationale: Diaphragm atrophy and dysfunction have been reported in humans during mechanical ventilation, but the prevalence, causes, and functional impact of changes in diaphragm thickness during routine mechanical ventilation for critically ill patients are unknown.

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2015 Oct 15 - Incidence and Prognostic Value of the Systemic Inflammatory Response Syndrome and Organ Dysfunctions in Ward Patients

Matthew M. Churpek, Frank J. Zadravecz, Christopher Winslow, Michael D. Howell, and Dana P. Edelson  Am. J. Resp. Crit. Care Med. Oct 15, 2015, vol. 192, no. 8: 958-964

Rationale: Tools that screen inpatients for sepsis use the systemic inflammatory response syndrome (SIRS) criteria and organ dysfunctions, but most studies of these criteria were performed in intensive care unit or emergency room populations.

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2015 Oct 15 - Acute Kidney Injury Requiring Dialysis in Severe Sepsis

Ankit Sakhuja, Gagan Kumar, Shipra Gupta, Tarun Mittal, Amit Taneja, and Rahul S. Nanchal  Am. J. Resp. Crit. Care Med. icine, Oct 15, 2015, vol. 192, no. 8: 951-957

Rationale: Understanding the changing incidence and impact of acute kidney injury requiring dialysis in patients with severe sepsis will allow better risk stratification, design of clinical trials, and guide resource allocation.

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2015 Oct 1 - A Molecular Biomarker to Diagnose Community-acquired Pneumonia on Intensive Care Unit Admission

Brendon P. Scicluna, Peter M. C. Klein Klouwenberg, Lonneke A. van Vught, Maryse A. Wiewel, David S. Y. Ong, Aeilko H. Zwinderman, Marek Franitza, Mohammad R. Toliat, Peter Nürnberg, Arie J. Hoogendijk, Janneke Horn, Olaf L. Cremer, Marcus J. Schultz, Marc J. Bonten, and Tom van der Poll  Am. J. Resp. Crit. Care Med. Oct 1, 2015, vol. 192, no. 7: 826-835

Rationale: Community-acquired pneumonia (CAP) accounts for a major proportion of intensive care unit (ICU) admissions for respiratory failure and sepsis. Diagnostic uncertainty complicates case management, which may delay appropriate cause-specific treatment.

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2015 Sep - Conservative Versus Liberal Oxygenation Targets for Mechanically Ventilated Patients - a Pilot Multicenter Randomized Controlled Trial

Panwar R, Hardie M, Bellomo R, Barrot L, Eastwood GM, Young PJ, Capellier G, Harrigan PW, Bailey M; CLOSE study investigators and the ANZICS Clinical Trials Group..; Am J Respir Crit Care Med. 2015 Sep 3. [Epub ahead of print]

RATIONALE: There are no randomized controlled trials (RCTs) comparing different oxygenation targets for Intensive Care Unit (ICU) patients.

OBJECTIVES: To determine whether a conservative oxygenation strategy is a feasible alternative to a liberal oxygenation strategy among ICU patients requiring invasive mechanical ventilation (IMV).

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2015 Sep 15 - Respiratory Electrodialysis. A Novel, Highly Efficient Extracorporeal CO2 Removal Technique

Alberto Zanella, Luigi Castagna, Domenico Salerno, Vittorio Scaravilli, Salua Abd El Aziz El Sayed Deab, Federico Magni, Marco Giani, Silvia Mazzola, Mariangela Albertini, Nicolò Patroniti, Francesco Mantegazza, and Antonio Pesenti  Am. J. Resp. Crit. Care Med. Sep 15, 2015, vol. 192, no. 6: 719-726

Rationale: We developed an innovative, minimally invasive, highly efficient extracorporeal CO2 removal (ECCO2R) technique called respiratory electrodialysis (R-ED).

Objectives: To evaluate the efficacy of R-ED in controlling ventilation compared with conventional ECCO2R technology.

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2015 Sep 1 - Hospitalization Type and Subsequent Severe Sepsis

Hallie C. Prescott, Robert P. Dickson, Mary A. M. Rogers, Kenneth M. Langa, and Theodore J. Iwashyna  Am. J. Resp. Crit. Care Med. Sep 1, 2015. vol. 192, no. 5: 581-588

Rationale: Hospitalization is associated with microbiome perturbation (dysbiosis), and this perturbation is more severe in patients treated with antimicrobials.

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2015 Aug 15 - Trends in Tracheostomy for Mechanically Ventilated Patients in the United States, 1993–2012

Anuj B. Mehta, Sohera N. Syeda, Lisa Bajpayee, Colin R. Cooke, Allan J. Walkey, and Renda Soylemez Wiener  Am. J. Resp. Crit. Care Med. Aug 15, 2015, vol. 192, no. 4: 446-454

Rationale: National trends in tracheostomy for mechanical ventilation (MV) patients are not well characterized.

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2015 Aug 1 - Therapeutic Effects of Human Mesenchymal Stem Cell–derived Microvesicles in Severe Pneumonia in Mice

Antoine Monsel, Ying-gang Zhu, Stephane Gennai, Qi Hao, Shuling Hu, Jean-Jacques Rouby, Michelle Rosenzwajg, Michael A. Matthay, and Jae W. Lee  Am. J. Resp. Crit. Care Med. Aug 1, 2015, vol. 192, no. 3: 324-336

Rationale: Microvesicles (MVs) are anuclear fragments of cells released from the endosomal compartment or shed from surface membranes. We and other investigators demonstrated that MVs released by mesenchymal stem cells (MSCs) were as effective as the cells themselves in inflammatory injuries, such as after endotoxin-induced acute lung injury. However, the therapeutic effects of MVs in an infectious model of acute lung injury remain unknown.

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2015 Aug 1 - Mechanical Stress and the Induction of Lung Fibrosis via the Midkine Signaling Pathway

Rong Zhang, Ying Pan, Vito Fanelli, Sulong Wu, Alice Aili Luo, Diana Islam, Bing Han, Pu Mao, Mirna Ghazarian, Wenmei Zeng, Peter M. Spieth, Dingyan Wang, Julie Khang, Hongyin Mo, Xiaoqing Liu, Stefan Uhlig, Mingyao Liu, John Laffey, Arthur S. Slutsky, Yimin Li, and Haibo Zhang  Am. J. Resp. Crit. Care Med. Aug 1, 2015, vol. 192, no. 3: 315-323

Rationale: Lung-protective ventilatory strategies have been widely used in patients with acute respiratory distress syndrome (ARDS), but the ARDS mortality rate remains unacceptably high and there is no proven pharmacologic therapy.

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2015 Jul 15 - Soluble Receptor for Advanced Glycation End-Products Predicts Impaired Alveolar Fluid Clearance in Acute Respiratory Distress Syndrome

Matthieu Jabaudon, Raiko Blondonnet, Laurence Roszyk, Damien Bouvier, Jules Audard, Gael Clairefond, Mathilde Fournier, Geoffroy Marceau, Pierre Déchelotte, Bruno Pereira, Vincent Sapin, and Jean-Michel Constantin  Am. J. Resp. Crit. Care Med. Jul 15, 2015, vol. 192, no. 2: 191-199

Rationale: Levels of the soluble form of the receptor for advanced glycation end-products (sRAGE) are elevated during acute respiratory distress syndrome (ARDS) and correlate with severity and prognosis. Alveolar fluid clearance (AFC) is necessary for the resolution of lung edema but is impaired in most patients with ARDS. No reliable marker of this process has been investigated to date.

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2015 Jul 1 - Determining the Ideal Strategy for Ventilator-associated Pneumonia Prevention. Cost–Benefit Analysis

Westyn Branch-Elliman, Sharon B. Wright, and Michael D. Howell  Am. J. Resp. Crit. Care Med. Jul 1, 2015, vol. 192, no. 1: 57-63

Rationale: Ventilator-associated pneumonia (VAP) is a common healthcare-associated infection with high associated cost and poor patient outcomes. Many strategies for VAP reduction have been evaluated. However, the combination of strategies with the optimal cost–benefit ratio remains unknown.

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2015 Jun 15 - Indications and Effects of Plasma Transfusions in Critically Ill Children

Oliver Karam, Pierre Demaret, Alison Shefler, Stéphane Leteurtre, Philip C. Spinella, Simon J. Stanworth, and Marisa Tucci  Am. J. Resp. Crit. Care Med. Jun 15, 2015, vol. 191, no. 12: 1395-1402

Rationale: Plasma transfusions are frequently prescribed for critically ill children, although their indications lack a strong evidence base. Plasma transfusions are largely driven by physician conceptions of need, and these are poorly documented in pediatric intensive care patients.

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2015 Jun 1 - Update in Sepsis and Acute Kidney Injury 2014

Frédérique Schortgen and Pierre Asfar  Am. J. Resp. Crit. Care Med. Jun 1, 2015; vol. 191, no. 11: 1226-1231

Sepsis and acute kidney injury (AKI) represent an important burden in intensive care unit clinical practices. The Journal published important contributions in sepsis for novel therapeutic approaches suggesting that combined molecular targets (e.g., dual inhibition of IL-1β and IL-18, and coadministration of endothelial progenitor cells and stromal cell–derived factor-1α analog) could perform better. The clinical effectiveness of 1,25-dihydroxyvitamin D was reported in a double-blind, randomized, placebo-controlled trial.

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2015 May 15 - Global Epidemiology of Pediatric Severe Sepsis: The Sepsis Prevalence, Outcomes, and Therapies Study

Scott L. Weiss, Julie C. Fitzgerald, John Pappachan, Derek Wheeler, Juan C. Jaramillo-Bustamante, Asma Salloo, Sunit C. Singhi, Simon Erickson, Jason A. Roy, Jenny L. Bush, Vinay M. Nadkarni, and Neal J. Thomas  Am. J. Resp. Crit. Care Med. May 15, 2015, vol. 191, no. 10: 1147-1157

Rationale: Limited data exist about the international burden of severe sepsis in critically ill children.

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2015 May 15 - Failure of Empirical Systemic Antifungal Therapy in Mechanically Ventilated Critically Ill Patients

Sébastien Bailly, Lila Bouadma, Elie Azoulay, Maité Garrouste Orgeas, Christophe Adrie, Bertrand Souweine, Carole Schwebel, Danièle Maubon, Rebecca Hamidfar-Roy, Michael Darmon, Michel Wolff, Muriel Cornet, and Jean-François Timsit  Am. J. Resp. Crit. Care Med. May 15, 2015, vol. 191, no. 10: 1139-1146

Rationale: Systemic antifungal treatments are empirically administered to the sickest critically ill patients, often without documented invasive fungal infection.

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2015 May 15 - Diaphragm Muscle Fiber Weakness and Ubiquitin–Proteasome Activation in Critically Ill Patients

Pleuni E. Hooijman, Albertus Beishuizen, Christian C. Witt, Monique C. de Waard, Armand R. J. Girbes, Angelique M. E. Spoelstra-de Man, Hans W. M. Niessen, Emmy Manders, Hieronymus W. H. van Hees, Charissa E. van den Brom, Vera Silderhuis, Michael W. Lawlor, Siegfried Labeit, Ger J. M. Stienen, Koen J. Hartemink, Marinus A. Paul, Leo M. A. Heunks, and Coen A. C. Ottenheijm  Am. J. Resp. Crit. Care Med. May 15, 2015, vol. 191, no. 10: 1126-1138

Rationale: The clinical significance of diaphragm weakness in critically ill patients is evident: it prolongs ventilator dependency, and increases morbidity and duration of hospital stay. To date, the nature of diaphragm weakness and its underlying pathophysiologic mechanisms are poorly understood.

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