2010 Dec 1 - Mechanical Ventilation–induced Diaphragm Disuse in Humans Triggers Autophagy

Sabah N. A. Hussain1,2, Mahroo Mofarrahi1,2, Ioanna Sigala3, Ho Cheol Kim4, Theodoros Vassilakopoulos3, Francois Maltais5, Ion Bellenis6, Rakesh Chaturvedi2, Stewart B. Gottfried1,2, Peter Metrakos7,8, Gawiyou Danialou1,9, Stefan Matecki10, Samir Jaber11, Basil J. Petrof1,2 and Peter Goldberg2.  American Journal of Respiratory and Critical Care Medicine Vol 182. pp. 1377-1386, (2010)
Rationale: Controlled mechanical ventilation (CMV) results in atrophy of the human diaphragm. The autophagy-lysosome pathway (ALP) contributes to skeletal muscle proteolysis, but its contribution to diaphragmatic protein degradation in mechanically ventilated patients is unknown.

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2010 Nov 1 - Inspiratory Resistive Breathing Induces Acute Lung Injury

Dimitris Toumpanakis1, George A. Kastis1, Panagiotis Zacharatos1, Ioanna Sigala1, Tatiana Michailidou1, Maroussa Kouvela1, Constantinos Glynos1, Maziar Divangahi1, Charis Roussos1, Stamatios E. Theocharis2 and Theodoros Vassilakopoulos1. American Journal of Respiratory and Critical Care Medicine Vol 182. pp. 1129-1136, (2010)
Rationale: Resistive breathing is associated with large negative intrathoracic pressures. Increased mechanical stress induces high-permeability pulmonary edema and lung inflammation.

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2010 Nov 1 - Pulmonary Vascular Dysfunction Is Associated with Poor Outcomes in Patients with Acute Lung Injury

Todd M. Bull1, Brendan Clark1, Kim McFann1, Marc Moss1 for the National Institutes of Health/National Heart, Lung, and Blood Institute ARDS Network. American Journal of Respiratory and Critical Care Medicine Vol 182. pp. 1123-1128, (2010)
Rationale: Despite the recognition that acute lung injury (ALI) can elevate pulmonary artery (PA) pressure and right ventricular afterload, the impact of pulmonary vascular dysfunction on outcomes of these patients is not well defined.

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2010 Oct 15 - Mesenchymal Stem Cells Reduce Inflammation while Enhancing Bacterial Clearance and Improving Survival in Sepsis

Shirley H. J. Mei1,4,*, Jack J. Haitsma2,*, Claudia C. Dos Santos2, Yupu Deng1, Patrick F. H. Lai4, Arthur S. Slutsky2,4, W. Conrad Liles3,4,5,# and Duncan J. Stewart1,4,#. Published ahead of print on June 17, 2010, doi:10.1164/rccm.201001-0010OC. American Journal of Respiratory and Critical Care Medicine Vol 182. pp. 1047-1057, (2010)

 Rationale: Sepsis refers to the clinical syndrome of severe systemic inflammation precipitated by infection. Despite appropriate antimicrobial therapy, sepsis-related morbidity and mortality remain intractable problems in critically ill patients. Moreover, there is no specific treatment strategy for the syndrome of sepsis-induced multiple organ dysfunction.

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2010 Oct 15 - Diagnostic Strategy for Hematology and Oncology Patients with Acute Respiratory Failure: Randomized Controlled Trial

Élie Azoulay1, Djamel Mokart2, Jérôme Lambert3, Virginie Lemiale4, Antoine Rabbat5, Achille Kouatchet6, François Vincent7, Didier Gruson8, Fabrice Bruneel9, Géraldine Epinette-Branche1, Ariane Lafabrie1, Rebecca Hamidfar-Roy10, Christophe Cracco11, Benoît Renard12, Jean-Marie Tonnelier13, François Blot14, Sylvie Chevret3 and Benoît Schlemmer1 Published ahead of print on June 25, 2010, doi:10.1164/rccm.201001-0018OC. American Journal of Respiratory and Critical Care Medicine Vol 182. pp. 1038-1046, (2010)

Rationale: Respiratory events are common in hematology and oncology patients and manifest as hypoxemic acute respiratory failure (ARF) in up to half the cases. Identifying the cause of ARF is crucial. Fiberoptic bronchoscopy with bronchoalveolar lavage (FO-BAL) is an invasive test that may cause respiratory deterioration. Recent noninvasive diagnostic tests may have modified the risk/benefit ratio of FO-BAL.

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2010 Oct 15 - Macrophage Migration Inhibitory Factor Promotes Tumor Growth in the Context of Lung Injury and Repair

Douglas Arenberg1,2, Tracy R. Luckhardt1,2, Shannon Carskadon1,2, Liujian Zhao1,2, Mohammad A. Amin2,3 and Alisa E. Koch2,3. Published ahead of print on June 25, 2010, doi:10.1164/rccm.201001-0120OC. American Journal of Respiratory and Critical Care Medicine Vol 182. pp. 1030-1037, (2010)
Rationale: Tissue injury and repair involve highly conserved processes governed by mechanisms that can be co-opted in tumors. We hypothesized that soluble factors released during the repair response to lung injury would promote orthotopic tumor growth.

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2010 Oct 15 - Critical Care Perspective: Toward an Integrated Research Agenda for Critical Illness in Aging

Eric B. Milbrandt1, Basil Eldadah2, Susan Nayfield2, Evan Hadley2 and Derek C. Angus1. Published ahead of print on June 17, 2010. American Journal of Respiratory and Critical Care Medicine Vol 182. pp. 995-1003, (2010)
Aging brings an increased predisposition to critical illness. Patients older than 65 years of age account for approximately half of all intensive care unit (ICU) admissions in the United States, a proportion that is expected to increase considerably with the aging of the population.

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The Chitinase-like Proteins Breast Regression Protein-39 and YKL-40 Regulate Hyperoxia-induced Acute Lung Injury

Myung Hyun Sohn1, Min-Jong Kang2, Hiroshi Matsuura2, Vineet Bhandari3, Ning-Yuan Chen2, Chun Geun Lee2 and Jack A. Elias2. American Journal of Respiratory and Critical Care Medicine Vol 182. pp. 918-928, (2010)

Rationale: Prolonged exposure to 100% O2 causes hyperoxic acute lung injury (HALI), characterized by alveolar epithelial cell injury and death. We previously demonstrated that the murine chitinase-like protein, breast regression protein (BRP)–39 and its human homolog, YKL-40, inhibit cellular apoptosis. However, the regulation and roles of these molecules in hyperoxia have not been addressed.

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2010 Oct 1 - Intermittent Subglottic Secretion Drainage and Ventilator-associated Pneumonia: A Multicenter Trial

Jean-Claude Lacherade1, Bernard De Jonghe1, Pierre Guezennec2, Karim Debbat3, Jan Hayon4, Antoine Monsel1, Pascal Fangio1, Corinne Appere de Vecchi1, Cédric Ramaut5, Hervé Outin1 and Sylvie Bastuji-Garin6. Published ahead of print on June 3, 2010, American Journal of Respiratory and Critical Care Medicine Vol 182. pp. 910-917, (2010)

Figure. The Hi-Lo® Evac tube (Mallinckrodt® Medical) used in the study
Rationale: Ventilator-associated pneumonia (VAP) causes substantial morbidity and mortality. The influence of subglottic secretion drainage (SSD) in preventing VAP remains controversial.

Objectives: To determine whether SSD reduces the overall incidence of microbiologically confirmed VAP.

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2010 Oct 1 - A Randomized Trial of Two Methods to Disclose Prognosis to Surrogate Decision Makers in Intensive Care Units

Susan J. Lee Char1, Leah R. Evans2, Grace L. Malvar3 and Douglas B. White4. American Journal of Respiratory and Critical Care Medicine Vol 182. pp. 905-909, (2010). Published ahead of print on June 10, 2010
Rationale: Surrogate decision makers and clinicians often have discordant perceptions about a patient's prognosis. There is a paucity of empirical data to guide communication about prognosis.

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2010 Sep 15 - Phosphoinositide-3 Kinase Activity Contributes to Sepsis and Organ Damage by Altering Neutrophil Recruitment

Erica L. Martin1,*, Danielle G. Souza2,*, Caio T. Fagundes2, Flavio A. Amaral2, Barbara Assenzio1, Valeria Puntorieri1, Lorenzo Del Sorbo1, Vito Fanelli1, Martino Bosco3, Luisa Delsedime3, Jose F. Pinho4, Virginia S. Lemos4, Fabricio O. Souto5, Jose C. Alves-Filho5, Fernando Q. Cunha5, Arthur S. Slutsky6, Thomas Ruckle7, Emilio Hirsch8, Mauro M. Teixeira2, and V. Marco Ranieri1. American Journal of Respiratory and Critical Care Medicine Vol 182. pp. 762-773, (2010). Published ahead of print on May 27, 2010, doi:10.1164/rccm.201001-0088OC
Rationale: Sepsis is a leading cause of death in the intensive care unit, characterized by a systemic inflammatory response (SIRS) and bacterial infection, which can often induce multiorgan damage and failure. Leukocyte recruitment, required to limit bacterial spread, depends on phosphoinositide-3 kinase (PI3K) signaling in vitro; however, the role of this enzyme in polymicrobial sepsis has remained unclear.

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2010 Sep 15 - Early Lactate-Guided Therapy in Intensive Care Unit Patients:A Multicenter, Open-Label, Randomized Controlled Trial

Tim C. Jansen1, Jasper van Bommel1, F. Jeanette Schoonderbeek3, Steven J. Sleeswijk Visser4, Johan M. van der Klooster5, Alex P. Lima1, Sten P. Willemsen2, Jan Bakker1 for the LACTATE study group* American Journal of Respiratory and Critical Care Medicine Vol 182. pp. 752-761, (2010). Published ahead of print on May 12, 2010, doi:10.1164/rccm.200912-1918OC
Rationale: It is unknown whether lactate monitoring aimed to decrease levels during initial treatment in critically ill patients improves outcome.

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2010 Sep 15 - Survival in Critical Illness Is Associated with Early Activation of Mitochondrial Biogenesis

Jane E. Carré1, Jean-Christophe Orban1,2, Lorenza Re1,3, Karen Felsmann4, Wiebke Iffert4, Michael Bauer5, Hagir B. Suliman6, Claude A. Piantadosi6, Terry M. Mayhew7, Patrick Breen1, Martin Stotz1 and Mervyn Singer1. American Journal of Respiratory and Critical Care Medicine Vol 182. pp. 745-751, (2010). Published ahead of print on June 10, 2010, doi:10.1164/rccm.201003-0326OC
Rationale: We previously reported outcome-associated decreases in muscle energetic status and mitochondrial dysfunction in septic patients with multiorgan failure. We postulate that survivors have a greater ability to maintain or recover normal mitochondrial functionality.

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2010 Aug 17 - Insulin-like Growth Factor–1 Levels Contribute to the Development of Bacterial Translocation in Sepsis

Gary W. Hunninghake1,3, Kevin C. Doerschug1, Amanda B. Nymon1, Gregory A. Schmidt1, David K. Meyerholz2 and Alix Ashare1. Published ahead of print on April 22, 2010, doi:10.1164/rccm.200911-1757OC. American Journal of Respiratory and Critical Care Medicine Vol 182. pp. 517-525, (2010)
Rationale: Many lines of evidence point toward the gastrointestinal (GI) tract in the pathophysiology of organ dysfunction in sepsis. Splanchnic hypoperfusion during sepsis leads to enterocyte apoptosis, diminished barrier function, and release of bacterial products. Sepsis lowers levels of insulin-like growth factor (IGF)–1, a known antiapoptotic factor. We recently demonstrated that treatment with IGF-1 is protective in murine sepsis.

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2010 Aug 17 - Alterations in Adipose Tissue during Critical Illness: An Adaptive and Protective Response?

Lies Langouche1, Sarah Vander Perre1, Steven Thiessen1, Jan Gunst1, Greet Hermans2, André D'Hoore3, Blerina Kola4, Márta Korbonits4 and Greet Van den Berghe1. Published ahead of print on May 4, 2010, doi:10.1164/rccm.200909-1395OC. American Journal of Respiratory and Critical Care Medicine Vol 182. pp. 507-516, (2010)
Rationale: Critical illness is characterized by lean tissue wasting, whereas adipose tissue is preserved. Overweight and obese critically ill patients may have a lower risk of death than lean patients, suggestive of a protective role for adipose tissue during illness.

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2010 Aug 17 - Outcomes of Critically Ill Patients Who Received Cardiopulmonary Resuscitation

Jianmin Tian1,*, David A. Kaufman1,*, Stuart Zarich1, Paul S. Chan1,2, Philip Ong1, Yaw Amoateng-Adjepong1, Constantine A. Manthous1 for the American Heart Association National Registry for Cardiopulmonary Resuscitation Investigators. American Journal of Respiratory and Critical Care Medicine Vol 182. pp. 501-506, (2010). Published ahead of print on April 22, 2010
Rationale: Studies examining survival outcomes after in-hospital cardiopulmonary arrest (CPA) among intensive care unit (ICU) patients requiring medications for hemodynamic support are limited.

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2010 Aug 17 - Activating Transcription Factor 3 Confers Protection against Ventilator-induced Lung Injury

Ali Akram1, Bing Han2, Hussain Masoom1, Claudia Peng1, Emily Lam1, Michael L. Litvack2, Xiaohui Bai2, Yuexin Shan1, Tsonwin Hai3, Jane Batt1, Arthur S. Slutsky1,4, Haibo Zhang1, Wolfgang M. Kuebler1, Jack J. Haitsma1, Mingyao Liu2 and Claudia C. dos Santos1,4. American Journal of Respiratory and Critical Care Medicine Vol 182. pp. 489-500, (2010). Published ahead of print on April 22, 2010.
Rationale: Ventilator-induced lung injury (VILI) significantly contributes to mortality in patients with acute respiratory distress syndrome, the most severe form of acute lung injury. Understanding the molecular basis for response to cyclic stretch (CS) and its derangement during high-volume ventilation is of high priority.

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2010 Aug 1 - Hydrogen Sulfide Improves Neutrophil Migration and Survival in Sepsis via K+ATP Channel Activation

Fernando Spiller1, Maria I. L. Orrico1, Daniele C. Nascimento1, Paula G. Czaikoski1, Fabrício O. Souto1, José C. Alves-Filho1, Andressa Freitas1, Daniela Carlos1, Marcelo F. Montenegro1, Alberto F. Neto2, Sergio H. Ferreira1, Marcos A. Rossi3, John S. Hothersall1, Jamil Assreuy4 and Fernando Q. Cunha1. Published ahead of print on March 25, 2010, doi:10.1164/rccm.200907-1145OC. American Journal of Respiratory and Critical Care Medicine Vol 182. pp. 360-368, (2010)
Rationale: Recovering the neutrophil migration to the infectious focus improves survival in severe sepsis. Recently, we demonstrated that the cystathionine -lyase (CSE)/hydrogen sulfide (H2S) pathway increased neutrophil recruitment to inflammatory focus during sterile inflammation.

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2010 Aug 1 - Intensive Insulin Therapy in Severely Burned Pediatric Patients: A Prospective Randomized Trial

Marc G. Jeschke1,2, Gabriela A. Kulp1,2,3, Robert Kraft1,2, Celeste C. Finnerty1,2, Ron Mlcak1,2, Jong O. Lee1,2 and David N. Herndon1,2. American Journal of Respiratory and Critical Care Medicine Vol 182. pp. 351-359, (2010). Published ahead of print on April 15, 2010, doi:10.1164/rccm.201002-0190OC
Rationale: Hyperglycemia and insulin resistance have been shown to increase morbidity and mortality in severely burned patients, and glycemic control appears essential to improve clinical outcomes. However, to date no prospective randomized study exists that determines whether intensive insulin therapy is associated with improved post-burn morbidity and mortality.

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2010 Aug 1 - Role for Myeloid Nuclear Differentiation Antigen in the Regulation of Neutrophil Apoptosis during Sepsis

Nasser Fotouhi-Ardakani1,*, Driss El Kebir1,*, Natacha Pierre-Charles1, Lili Wang1, Stephane P. Ahern2, János G. Filep1,3, and Eric Milot1,4. Published ahead of print on April 15, 2010, doi:10.1164/rccm.201001-0075OC. American Journal of Respiratory and Critical Care Medicine Vol 182. pp. 341-350, (2010)
Rationale: Suppressed neutrophil apoptosis, a hallmark of sepsis, perpetuates inflammation and delays resolution. Myeloid nuclear differentiation antigen (MNDA) is expressed only in myeloid cells and has been implicated in cell differentiation; however, its function in mature neutrophils is not known.

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