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.
Rationale: Resistive breathing is associated with large negative intrathoracic pressures. Increased mechanical stress induces high-permeability pulmonary edema and lung inflammation.
2010 Nov 1 - Pulmonary Vascular Dysfunction Is Associated with Poor Outcomes in Patients with Acute Lung Injury
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.
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.
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.
2010 Oct 15 - Macrophage Migration Inhibitory Factor Promotes Tumor Growth in the Context of Lung Injury and Repair
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.
2010 Oct 15 - Critical Care Perspective: Toward an Integrated Research Agenda for Critical Illness in Aging
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.
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.
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.
2010 Oct 1 - A Randomized Trial of Two Methods to Disclose Prognosis to Surrogate Decision Makers in Intensive Care Units
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.
2010 Sep 15 - Phosphoinositide-3 Kinase Activity Contributes to Sepsis and Organ Damage by Altering Neutrophil Recruitment
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.
2010 Sep 15 - Early Lactate-Guided Therapy in Intensive Care Unit Patients:A Multicenter, Open-Label, Randomized Controlled Trial
Rationale: It is unknown whether lactate monitoring aimed to decrease levels during initial treatment in critically ill patients improves outcome.
2010 Sep 15 - Survival in Critical Illness Is Associated with Early Activation of Mitochondrial Biogenesis
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.
2010 Aug 17 - Insulin-like Growth Factor–1 Levels Contribute to the Development of Bacterial Translocation in Sepsis
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.
2010 Aug 17 - Alterations in Adipose Tissue during Critical Illness: An Adaptive and Protective Response?
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.
Rationale: Studies examining survival outcomes after in-hospital cardiopulmonary arrest (CPA) among intensive care unit (ICU) patients requiring medications for hemodynamic support are limited.
2010 Aug 17 - Activating Transcription Factor 3 Confers Protection against Ventilator-induced Lung Injury
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.
2010 Aug 1 - Hydrogen Sulfide Improves Neutrophil Migration and Survival in Sepsis via K+ATP Channel Activation
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.
2010 Aug 1 - Intensive Insulin Therapy in Severely Burned Pediatric Patients: A Prospective Randomized Trial
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.
2010 Aug 1 - Role for Myeloid Nuclear Differentiation Antigen in the Regulation of Neutrophil Apoptosis during Sepsis
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.