Critical care : the official journal of the Critical Care Forum
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Angiopoietin-1 (Angpt1), the natural agonist ligand for the endothelial Tie2 receptor, is a non-redundant endothelial survival and vascular stabilization factor that reduces endothelial permeability and inhibits leukocyte-endothelium interactions. Here we evaluate the efficacy of a novel polyethylene glycol (PEG)-clustered Tie2 agonist peptide, Vasculotide (VT), to protect against vascular leakage and mortality in a murine model of polymicrobial abdominal sepsis. ⋯ We provide proof of principle in support of the efficacious use of PEGylated VT, a drug-like Tie2 receptor agonist, to counteract microvascular endothelial barrier dysfunction and reduce mortality in a clinically relevant murine sepsis model. Further studies are needed to pave the road for clinical application of this therapeutic concept.
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Mortality associated with nosocomial bloodstream infection is multifactorial. Source of infection, etiology, age, underlying disease, acute illness, and appropriateness of antimicrobial therapy all contribute to the final outcome. ⋯ Yet, in settings with a high standard of care in terms of infection prevention and control, the occurrence rate of bloodstream infection is relatively low and therefore its impact on overall ICU mortality rather limited. As a consequence, untargeted interventional studies focused on infection prevention should use occurrence rate of infection rather than mortality as outcome variable.
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Vitamin D deficiency is highly prevalent among critically ill patients and may be associated with adverse outcomes. Failure of conventional vitamin D supplementation in correcting deficiency has called for studies to evaluate the efficacy and safety of a high-dose regime in critically ill patients. High-dose vitamin D supplementation that corrects a deficient state effectively and safely allows for intervention studies to be undertaken to determine the impact of vitamin D on morbidity and mortality in critically ill patients.
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Editorial Comment
Positioning of patients with acute respiratory distress syndrome: combining prone and upright makes sense.
Positional strategies have been proposed for mechanically ventilated patients with acute respiratory distress syndrome. Despite different physiological mechanisms involved, oxygenation improvement has been demonstrated with both prone and upright positions. ⋯ The combined positioning enhanced the response rate in terms of oxygenation. Other benefits, such as a reduction in ventilator-associated pneumonia and better enteral feeding tolerance, can potentially be expected.