2009 Sep - Granulocyte–Macrophage Colony-stimulating Factor to Reverse Sepsis-associated Immunosuppression: A Double-Blind, Randomized, Placebo-controlled Multicenter Trial
Rationale: Sustained sepsis-associated immunosuppression is associated with uncontrolled infection, multiple organ dysfunction, and death.
Objectives: In the first controlled biomarker-guided immunostimulatory trial in sepsis, we tested whether granulocyte–macrophage colony-stimulating factor (GM-CSF) reverses monocyte deactivation, a hallmark of sepsis-associated immunosuppression (primary endpoint), and improves the immunological and clinical course of patients with sepsis.
Rationale: Vasopressin has been proposed as a potent vasoactive agent in the treatment of vasodilatory shock in adults and children. The objective of this trial was to evaluate the efficacy and safety of vasopressin as an adjunctive agent in pediatric vasodilatory shock.
Methods: In this multicenter, double-blind trial, children with vasodilatory shock were randomized to receive low-dose vasopressin (0.0005–0.002 U/kg/min) or placebo in addition to open-label vasoactive agents. Vasoactive infusions were titrated to clinical endpoints of adequate perfusion. The primary outcome was time to vasoactive-free hemodynamic stability. Secondary outcomes included mortality, organ-failure–free days, length of critical care unit stay, and adverse events.
2009 Sep - [18F]Fluorodeoxyglucose Positron Emission Tomography for Lung Antiinflammatory Response Evaluation
Rationale: Few noninvasive biomarkers for pulmonary inflammation are currently available that can assess the lung-specific response to antiinflammatory treatments. Positron emission tomography with [18F]fluorodeoxyglucose (FDG-PET) is a promising new method that can be used to quantify pulmonary neutrophilic inflammation.
Objectives: To evaluate the ability of FDG-PET to measure the pulmonary antiinflammatory effects of hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) and recombinant human activated protein C (rhAPC) in a human model of experimentally-induced lung inflammation.
2009 Sep - Macrophage Tumor Necrosis Factor- Induces Epithelial Expression of Granulocyte–Macrophage Colony-stimulating Factor: Impact on Alveolar Epithelial Repair
Rationale: Resident alveolar macrophages have been attributed a crucial role in host defense toward pulmonary infection. Their contribution to alveolar repair processes, however, remains elusive.
Objectives: We investigated whether activated resident alveolar macrophages contribute to alveolar epithelial repair on lipopolysaccharide (LPS) challenge in vitro and in vivo and analyzed the molecular interaction pathways involved.
Methods: We evaluated macrophage–epithelial cross-talk mediators for epithelial cell proliferation in an in vitro coculture system and an in vivo model of LPS-induced acute lung injury comparing wild-type, granulocyte–macrophage colony-stimulating factor (GM-CSF)–deficient (GM–/–), and human SPC–GM mice (GM–/– mice expressing an SPC-promotor–regulated GM-CSF transgene).
Recommended by Dr SHUM Hoi Ping on 17 June 2009. Lott JP, Iwashyna TJ, Christie JD, Asch DA, Kramer AA, Kahn JM. Am J Respir Crit Care Med. 2009 Apr 15;179(8):676-83. Epub 2009 Feb 6
RATIONALE: General intensive care units (ICUs) provide care across a wide range of diagnoses, whereas specialty ICUs provide diagnosis-specific care. Risk-adjusted outcome differences across such units are unknown.
OBJECTIVES: To determine the association between specialty ICU care and the outcome of critical illness.
American Journal of Respiratory and Critical Care Medicine Vol 179. pp. 743-758, (2009)
Robert A. Fowler1, Neill K. J. Adhikari1, Damon C. Scales1, Warren L. Lee1 and Gordon D. Rubenfeld1
1 Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada