Critical care medicine
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Critical care medicine · Jul 2015
Randomized Controlled TrialDrug Repurposing Screen Identifies Foxo1-Dependent Angiopoietin-2 Regulation in Sepsis.
The recent withdrawal of a targeted sepsis therapy has diminished pharmaceutical enthusiasm for developing novel drugs for the treatment of sepsis. Angiopoietin-2 is an endothelial-derived protein that potentiates vascular inflammation and leakage and may be involved in sepsis pathogenesis. We screened approved compounds for putative inhibitors of angiopoietin-2 production and investigated underlying molecular mechanisms. ⋯ 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors may operate through a novel Foxo1-angiopoietin-2 mechanism to suppress de novo production of angiopoietin-2 and thereby ameliorate manifestations of sepsis. Given angiopoietin-2's dual role as a biomarker and candidate disease mediator, early serum angiopoietin-2 measurement may serve as a stratification tool for future trials of drugs targeting vascular leakage.
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Critical care medicine · Jul 2015
Temporal Changes in the Influence of Hospitals and Regional Healthcare Networks on Severe Sepsis Mortality.
There is systematic variation between hospitals in their care of severe sepsis, but little information on whether this variation impacts sepsis-related mortality, or how hospitals' and health-systems' impacts have changed over time. We examined whether hospital and regional organization of severe sepsis care is associated with meaningful differences in 30-day mortality in a large integrated health care system, and the extent to which those effects are stable over time. ⋯ In this large integrated healthcare system, there is clinically significant variation in sepsis-related mortality associated with hospitals and regions. The proportion of variance explained by hospitals and regions has been stable over time, although sepsis-related mortality has declined.
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Critical care medicine · Jul 2015
Observational StudyEffect of Early Intervention on Long-Term Outcomes of Critically Ill Cancer Patients Admitted to ICUs.
The objective of this observational study was to evaluate whether early intervention was associated with improved long-term outcomes in critically ill patients with cancer. ⋯ Early intervention for clinical derangement on general wards was significantly associated with long-term outcomes in critically ill cancer patients.