2011 Apr 15 - Disability among Elderly Survivors of Mechanical Ventilation

Amber E. Barnato1,2,3, Steven M. Albert4, Derek C. Angus1,2,3, Judith R. Lave1,3 and Howard B. Degenholtz1,3. Published ahead of print on November 5, 2010, doi:10.1164/rccm.201002-0301OC. American Journal of Respiratory and Critical Care Medicine Vol 183. pp. 1037-1042, (2011)
Rationale: Studies of long-term functional outcomes of elderly survivors of mechanical ventilation (MV) are limited to local samples and biased retrospective, proxy-reported preadmission functional status.

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2011 Apr 1 - Loss of Suppression of Tumorigenicity 2 (ST2) Gene Reverses Sepsis-induced Inhibition of Lung Host Defense in Mice

Jacobien J. Hoogerwerf1,2, Masja Leendertse1,2, Catharina W. Wieland1,2, Alex F. de Vos1,2, J. Daan de Boer1,2, Sandrine Florquin3 and Tom van der Poll1,2 Published ahead of print on October 19, 2010, doi:10.1164/rccm.201006-0934OC. American Journal of Respiratory and Critical Care Medicine Vol 183. pp. 932-940, (2011)
Rationale: After surviving the initial hyperinflammatory phase, patients with sepsis display features consistent with immunosuppression, which renders the host susceptible to nosocomial infections, in particular bacterial pneumonia. Suppression of tumorigenicity 2 (ST2) is a negative regulator of Toll-like receptor signaling implicated in endotoxin tolerance.

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2011 Apr 1 - Inhibition of Neutrophil Migration by Hemopexin Leads to Increased Mortality Due to Sepsis in Mice

Fernando Spiller1, Carlotta Costa2, Fabrício O. Souto1, Francesca Vinchi2, Fabíola L. A. C. Mestriner1, Helen J. Laure3,4, José C. Alves-Filho1, Andressa Freitas1, José C. Rosa3–5, Sérgio H. Ferreira1, Fiorella Altruda2, Emilio Hirsch2, Lewis J. Greene3–5, Emanuela Tolosano2,* and Fernando Q. Cunha1,* American Journal of Respiratory and Critical Care Medicine Vol 183. pp. 922-931, (2011). Published ahead of print on October 22, 2010, doi:10.1164/rccm.201002-0223OC
Rationale: The reduction of neutrophil migration to the bacterial focus is associated with poor outcome in sepsis.

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2011 Apr 1 - An Empirical Study of Surrogates' Preferred Level of Control over Value-laden Life Support Decisions in Intensive Care Units

Sara K. Johnson1, Christopher A. Bautista2, Seo Yeon Hong3, Lisa Weissfeld3 and Douglas B. White4. American Journal of Respiratory and Critical Care Medicine Vol 183. pp. 915-921, (2011). Published ahead of print on October 29, 2010, doi:10.1164/rccm.201008-1214OC
Rationale: Despite ongoing ethical debate concerning who should control decisions to discontinue life support for incapacitated, critically ill patients, the perspectives of surrogate decision makers are poorly understood.

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2011 Apr 1 - Neutrophil Gelatinase-associated Lipocalin at ICU Admission Predicts for Acute Kidney Injury in Adult Patients

Hilde R. H. de Geus1, Jan Bakker1, Emmanuel M. E. H. Lesaffre2,3 and Jos L. M. L. le Noble1. American Journal of Respiratory and Critical Care Medicine Vol 183. pp. 907-914, (2011). Published ahead of print on October 8, 2010, doi:10.1164/rccm.200908-1214OC
Rationale: Measured at intensive care unit admission (ICU), the predictive value of neutrophil gelatinase-associated lipocalin (NGAL) for severe acute kidney injury (AKI) is unclear.

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2011 Mar 15 - EGFR Tyrosine Kinase Inhibition Worsens Acute Lung Injury in Mice with Repairing Airway Epithelium

Chika Harada1, Tomonobu Kawaguchi1, Saiko Ogata-Suetsugu1, Mizuho Yamada1, Naoki Hamada1, Takashige Maeyama1, Ryota Souzaki2, Tatsuro Tajiri2, Tomoaki Taguchi2, Kazuyoshi Kuwano3 and Yoichi Nakanishi1. Published ahead of print on October 8, 2010, doi:10.1164/rccm.201002-0188OC. American Journal of Respiratory and Critical Care Medicine Vol 183. pp. 743-751, (2011)
Rationale: Epidermal growth factor receptor (EGFR) and its ligands play important roles in the regeneration of damaged epithelium and proliferation of various epithelial tumors. Although the EGFR-tyrosine kinase inhibitor gefitinib is effective against advanced non–small cell lung cancer with EGFR mutations, some patients treated with this agent develop severe acute interstitial pneumonia. Characteristics of patients who develop interstitial pneumonia include older age, smoking history, and preexisting interstitial pneumonia suggesting a connection between airway injury and alveolar dysfunction.

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2011 Mar 1 - A Randomized Clinical Trial of Hydroxymethylglutaryl– Coenzyme A Reductase Inhibition for Acute Lung Injury (The HARP Study)

Thelma R. Craig1,2, Martin J. Duffy1,2, Murali Shyamsundar1,2, Cliona McDowell3, Cecilia M. O'Kane2, J. Stuart Elborn2 and Daniel F. McAuley1,2 Published ahead of print on September 24, 2010. American Journal of Respiratory and Critical Care Medicine Vol 183. pp. 620-626, (2011)
Rationale: There is no effective pharmacological treatment for acute lung injury (ALI). Statins are a potential new therapy because they modify many of the underlying processes important in ALI.

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2011 Feb 15 - Increased Proteolysis, Myosin Depletion, and Atrophic AKT-FOXO Signaling in Human Diaphragm Disuse

Sanford Levine1,2,3,4, Chhanda Biswas1,3,4, Jamil Dierov1,3, Robert Barsotti4,5, Joseph B. Shrager1,3,4,6, Taitan Nguyen1,3, Seema Sonnad1, John C. Kucharchzuk1, Larry R. Kaiser1,7, Sunil Singhal1,3,* and Murat T. Budak1,3,4,* Published ahead of print on September 10, 2010, doi:10.1164/rccm.200910-1487OC. American Journal of Respiratory and Critical Care Medicine Vol 183. pp. 483-490, (2011)
Rationale: Patients on mechanical ventilation who exhibit diaphragm inactivity for a prolonged time (case subjects) develop decreases in diaphragm force-generating capacity accompanied by diaphragm myofiber atrophy.

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2011 Feb 15 - Neuroimmune Regulation of Ventilator-induced Lung Injury

Claudia C. dos Santos1,2, Yuexin Shan1,2, Ali Akram1,2, Arthur S. Slutsky1,2 and Jack J. Haitsma1,2 Published ahead of print on September 24, 2010.American Journal of Respiratory and Critical Care Medicine Vol 183. pp. 471-482, (2011)
Rationale: Ventilator-induced lung injury (VILI) contributes to the mortality in patients with acute lung injury by increasing inflammation. Recent evidence suggests that stimulation of the cholinergic antiinflammatory pathway may be an attractive way to attenuate inflammatory injury.

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2011 Feb 15 - Early Identification of Patients at Risk of Acute Lung Injury: Evaluation of Lung Injury Prediction Score in a Multicenter Cohort Study

Ognjen Gajic1, Ousama Dabbagh2, Pauline K. Park3, Adebola Adesanya4, Steven Y. Chang5, Peter Hou6, Harry Anderson, III7, J. Jason Hoth8, Mark E. Mikkelsen9, Nina T. Gentile10, Michelle N. Gong11, Daniel Talmor12, Ednan Bajwa13, Timothy R. Watkins14, Emir Festic15, Murat Yilmaz16, Remzi Iscimen17, David A. Kaufman18, Annette M. Esper19, Ruxana Sadikot20, Ivor Douglas21, Jonathan Sevransky22 and Michael Malinchoc1; on behalf of the U.S. Critical Illness and Injury Trials Group: Lung Injury Prevention Study Investigators (USCIITG–LIPS),* Published ahead of print on August 27, 2010. American Journal of Respiratory and Critical Care Medicine Vol 183. pp. 462-470, (2011)
Rationale: Accurate, early identification of patients at risk for developing acute lung injury (ALI) provides the opportunity to test and implement secondary prevention strategies.

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2011 Feb 1 - Rapidly Progressive Diaphragmatic Weakness and Injury during Mechanical Ventilation in Humans

Samir Jaber1,2,6, Basil J. Petrof3, Boris Jung1,2, Gérald Chanques1,2, Jean-Philippe Berthet4, Christophe Rabuel5, Hassan Bouyabrine6, Patricia Courouble1,2, Christelle Koechlin-Ramonatxo7, Mustapha Sebbane1,2, Thomas Similowski8, Valérie Scheuermann9, Alexandre Mebazaa5, Xavier Capdevila1,2, Dominique Mornet2, Jacques Mercier2,10, Alain Lacampagne9, Alexandre Philips2 and Stefan Matecki2,10. American Journal of Respiratory and Critical Care Medicine Vol 183. pp. 364-371, (2011). Published ahead of print on September 2, 2010, doi:10.1164/rccm.201004-0670OC
Rationale: Diaphragmatic function is a major determinant of the ability to successfully wean patients from mechanical ventilation (MV). Paradoxically, MV itself results in a rapid loss of diaphragmatic strength in animals. However, very little is known about the time course or mechanistic basis for such a phenomenon in humans.

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2011 Feb 1 - Genetic Variation in the FAS Gene and Associations with Acute Lung Injury

Bradford J. Glavan1, Tarah D. Holden1, Christopher H. Goss2, R. Anthony Black3, Margaret J. Neff1, Avery B. Nathens4, Thomas R. Martin5, Mark M. Wurfel1 ARDSnet Investigators. American Journal of Respiratory and Critical Care Medicine Vol 183. pp. 356-363, (2011). Published ahead of print on September 2, 2010, doi:10.1164/rccm.201003-0351OC
Rationale: Fas (CD95) modulates apoptosis and inflammation and is believed to play an important role in lung injury.

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2011 Feb 1 - Effect of a Quality-Improvement Intervention on End-of-Life Care in the Intensive Care Unit: A Randomized Trial

J. Randall Curtis1,2, Elizabeth L. Nielsen1, Patsy D. Treece1, Lois Downey1, Danae Dotolo1, Sarah E. Shannon2, Anthony L. Back3, Gordon D. Rubenfeld4 and Ruth A. Engelberg1. American Journal of Respiratory and Critical Care Medicine Vol 183. pp. 348-355, (2011). Published ahead of print on September 10, 2010, doi:10.1164/rccm.201006-1004OC
Rationale: Because of high mortality, end-of-life care is an important component of intensive care.

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2011 Feb 1 - Bedside Ultrasound Assessment of Positive End-Expiratory Pressure–induced Lung Recruitment

Belaïd Bouhemad1, Hélène Brisson1, Morgan Le-Guen1, Charlotte Arbelot1, Qin Lu1 and Jean-Jacques Rouby1. Published ahead of print on September 17, 2010, doi:10.1164/rccm.201003-0369OC. American Journal of Respiratory and Critical Care Medicine Vol 183. pp. 341-347, (2011)
Rationale: In the critically ill patients, lung ultrasound (LUS) is increasingly being used at the bedside for assessing alveolar-interstitial syndrome, lung consolidation, pneumonia, pneumothorax, and pleural effusion. It could be an easily repeatable noninvasive tool for assessing lung recruitment.

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2011 Jan 1 - An Official American Thoracic Society Statement: Treatment of Fungal Infections in Adult Pulmonary and Critical Care Patients

Andrew H. Limper, Kenneth S. Knox, George A. Sarosi, Neil M. Ampel, John E. Bennett, Antonino Catanzaro, Scott F. Davies, William E. Dismukes, Chadi A. Hage, Kieren A. Marr, Christopher H. Mody, John R. Perfect, David A. Stevens on behalf of the American Thoracic Society Fungal Working Group. American Journal of Respiratory and Critical Care Medicine Vol 183. pp. 96-128, (2011)
With increasing numbers of immune-compromised patients with malignancy, hematologic disease, and HIV, as well as those receiving immunosupressive drug regimens for the management of organ transplantation or autoimmune inflammatory conditions, the incidence of fungal infections has dramatically increased over recent years.

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2011 Jan 15 - Essential Role of CCR2 in Neutrophil Tissue Infiltration and Multiple Organ Dysfunction in Sepsis

Fabricio O. Souto1,2,*, José C. Alves-Filho2,3,*, Walter M. Turato4, Maria Auxiliadora-Martins1, Aníbal Basile-Filho1 and Fernando Q. Cunha2. Published ahead of print on August 23, 2010, doi:10.1164/rccm.201003-0416OC. American Journal of Respiratory and Critical Care Medicine Vol 183. pp. 234-242, (2011)
Rationale: Sepsis is defined as a systemic inflammatory response to infection, which in its severe form is associated with multiple organ dysfunction syndrome (MODS). The precise mechanisms by which MODS develops remain unclear. Neutrophils have a pivotal role in the defense against infections; however, overwhelming activation of neutrophils is known to elicit tissue damage.

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2011 Jan 15 - Staphylococcus aureus Sepsis and Mitochondrial Accrual of the 8-Oxoguanine DNA Glycosylase DNA Repair Enzyme in Mice

Raquel R. Bartz1,2, Hagir B. Suliman1, Ping Fu1, Karen Welty-Wolf2, Martha Sue Carraway2, Nancy Chou MacGarvey2, Crystal M. Withers3, Timothy E. Sweeney3 and Claude A. Piantadosi1,2,3. Published ahead of print on August 23, 2010, doi:10.1164/rccm.200911-1709OC. American Journal of Respiratory and Critical Care Medicine Vol 183. pp. 226-233, (2011)
Rationale: Damage to mitochondrial DNA (mtDNA) by the production of reactive oxygen species during inflammatory states, such as sepsis, is repaired by poorly understood mechanisms.

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2011 Jan 1 - Eight-Year Trend of Acute Respiratory Distress Syndrome: A Population-based Study in Olmsted County, Minnesota

Guangxi Li1,2, Michael Malinchoc1,3, Rodrigo Cartin-Ceba1, Chakradhar V. Venkata1, Daryl J. Kor1,4, Steve G. Peters1, Rolf D. Hubmayr1 and Ognjen Gajic1. Published ahead of print on August 6, 2010, doi:10.1164/rccm.201003-0436OC. American Journal of Respiratory and Critical Care Medicine Vol 183. pp. 59-66, (2011)
Rationale: Significant progress has been made in understanding the pathogenesis of acute respiratory distress syndrome (ARDS). Recent advances in hospital practice may have reduced the incidence of this lethal syndrome.

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2010 Dec 15 - Urokinase-Type Plasminogen Activator Inhibits Efferocytosis of Neutrophils

Yanping Yang1,*, Arnaud Friggeri1,2,*, Sami Banerjee1, Khalil Bdeir3, Douglas B. Cines3, Gang Liu1 and Edward Abraham1. Published ahead of print on July 23, 2010, doi:10.1164/rccm.201003-0452OC. American Journal of Respiratory and Critical Care Medicine Vol 182. pp. 1516-1523, (2010)
Rationale: Phagocytosis of apoptotic cells, also called efferocytosis, plays an essential role in the resolution of inflammation. Urokinase-type plasminogen activator (uPA) is a multifunctional protein that has been implicated in inflammatory conditions, including pneumonia and severe infection, which are often accompanied by the development of acute lung injury. However, the role of uPA in modulating efferocytosis of apoptotic neutrophils has not been defined.

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2010 Dec 15 - Protective Role of Peroxisome Proliferator–activated Receptor-β/ in Septic Shock

Amar Kapoor1, Yasunori Shintani1, Massimo Collino2, Marcin F. Osuchowski3, Daniel Busch3, Nimesh S. A. Patel1, Bruno Sepodes4, Sara Castiglia2, Roberto Fantozzi2, David Bishop-Bailey1, Helder Mota-Filipe4, Muhammad M. Yaqoob1, Ken Suzuki1, Soheyl Bahrami3, Béatrice Desvergne5, Jane A. Mitchell6 and Christoph Thiemermann1. Published ahead of print on August 6, 2010, doi:10.1164/rccm.201002-0240OC. American Journal of Respiratory and Critical Care Medicine Vol 182. pp. 1506-1515, (2010)
Rationale: Peroxisome proliferator–activated receptor (PPAR)-β/ is a transcription factor that belongs to the PPAR nuclear hormone receptor family, but the role of PPAR-β/ in sepsis is unknown.

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