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.
2011 Apr 1 - Loss of Suppression of Tumorigenicity 2 (ST2) Gene Reverses Sepsis-induced Inhibition of Lung Host Defense in Mice
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.
2011 Apr 1 - Inhibition of Neutrophil Migration by Hemopexin Leads to Increased Mortality Due to Sepsis in Mice
Rationale: The reduction of neutrophil migration to the bacterial focus is associated with poor outcome in sepsis.
2011 Apr 1 - An Empirical Study of Surrogates' Preferred Level of Control over Value-laden Life Support Decisions in Intensive Care Units
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.
2011 Apr 1 - Neutrophil Gelatinase-associated Lipocalin at ICU Admission Predicts for Acute Kidney Injury in Adult Patients
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.
2011 Mar 15 - EGFR Tyrosine Kinase Inhibition Worsens Acute Lung Injury in Mice with Repairing Airway Epithelium
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.
2011 Mar 1 - A Randomized Clinical Trial of Hydroxymethylglutaryl– Coenzyme A Reductase Inhibition for Acute Lung Injury (The HARP Study)
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.
2011 Feb 15 - Increased Proteolysis, Myosin Depletion, and Atrophic AKT-FOXO Signaling in Human Diaphragm Disuse
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.
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.
2011 Feb 15 - Early Identification of Patients at Risk of Acute Lung Injury: Evaluation of Lung Injury Prediction Score in a Multicenter Cohort Study
Rationale: Accurate, early identification of patients at risk for developing acute lung injury (ALI) provides the opportunity to test and implement secondary prevention strategies.
2011 Feb 1 - Rapidly Progressive Diaphragmatic Weakness and Injury during Mechanical Ventilation in Humans
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.
Rationale: Fas (CD95) modulates apoptosis and inflammation and is believed to play an important role in lung injury.
2011 Feb 1 - Effect of a Quality-Improvement Intervention on End-of-Life Care in the Intensive Care Unit: A Randomized Trial
Rationale: Because of high mortality, end-of-life care is an important component of intensive care.
2011 Feb 1 - Bedside Ultrasound Assessment of Positive End-Expiratory Pressure–induced Lung Recruitment
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.
2011 Jan 1 - An Official American Thoracic Society Statement: Treatment of Fungal Infections in Adult Pulmonary and Critical Care Patients
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.
2011 Jan 15 - Essential Role of CCR2 in Neutrophil Tissue Infiltration and Multiple Organ Dysfunction in Sepsis
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.
2011 Jan 15 - Staphylococcus aureus Sepsis and Mitochondrial Accrual of the 8-Oxoguanine DNA Glycosylase DNA Repair Enzyme in Mice
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.
2011 Jan 1 - Eight-Year Trend of Acute Respiratory Distress Syndrome: A Population-based Study in Olmsted County, Minnesota
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.
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.
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.