Evaluation of the Benefits of De-Escalation for Patients with Sepsis in the Emergency Intensive Care Unit.

PURPOSE: Although the 2016 Japanese guidelines for the management of sepsis recommend de-escalation of treatment after identification of the causative pathogen, adherence to this practice remain unknown. The objective of this study was to evaluate the benefits of de-escalating treatment for sepsis patients at an advanced critical care and emergency medical centre. METHODS: Based on electronic patient information, 85 patients who were transported to the centre by ambulance, and diagnosed with sepsis between January 2008 and September 2013 were enrolled and evaluated. Patients were divided into two groups with and without de-escalation, and comparisons were conducted for several variables, including length of hospital stay, and length of antibiotic administration. Two types of subgroup analysis were conducted between patients with septic shock or positive blood cultures. Statistical analysis was conducted using chi-square and Mann-Whitney U tests. RESULTS: The length of hospital stay after diagnosis was significantly shorter for the de-escalation group than for the non-de-escalation group. In the subgroup analysis, de-escalation for blood culture-positive patients was beneficial in terms of the length of hospital stay and length of antibiotic administration. CONCLUSIONS: The findings of this study suggest that sepsis treatment de-escalation is beneficial for treatment efficacy and appropriate use of antibiotics. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

HSP105 prevents depression-like behavior by increasing hippocampal brain-derived neurotrophic factor levels in mice.

Heat shock proteins (HSPs) are stress-induced chaperones that are involved in neurological disease. Although increasingly implicated in behavioral disorders, the mechanisms of HSP action, and the relevant functional pathways, are still unclear. We examined whether oral administration of geranylgeranylacetone (GGA), a known HSP inducer, produced an antidepressant effect in a social defeat stress model of depression in mice. We also investigated the possible molecular mechanisms involved, particularly focusing on hippocampal neurogenesis and neurotrophic factor expression. In stressed mice, hippocampal HSP105 expression decreased. However, administration of GGA increased HSP105 expression and improved depression-like behavior, induced hippocampal cell proliferation, and elevated brain-derived neurotrophic factor (BDNF) levels in mouse hippocampus. Co-treatment with GGA and the BDNF receptor inhibitor K252a suppressed the antidepressant effects of GGA. HSP105 knockdown decreased BDNF mRNA levels in HT22 hippocampal cell lines and hippocampal tissue and inhibited the GGA-mediated antidepressant effect. These observations suggest that GGA administration is a therapeutic candidate for depressive diseases by increasing hippocampal BDNF levels via HSP105 expression.