Dermal fibroblast-like cells reprogrammed directly from adipocytes in mouse.

In deep burns, early wound closure is important for healing, and skin grafting is mainly used for wound closure. However, it is difficult to achieve early wound closure in extensive total body surface area deep burns due to the lack of donor sites. Dermal fibroblasts, responsible for dermis formation, may be lost in deep burns. However, fat layers composed of adipocytes, lying underneath the dermis, are retained even in such cases. Direct reprogramming is a novel method for directly reprograming some cells into other types by introducing specific master regulators; it has exhibited appreciable success in various fields. In this study, we aimed to assess whether the transfection of master regulators (ELF4, FOXC2, FOXO1, IRF1, PRRX1, and ZEB1) could reprogram mouse adipocytes into dermal fibroblast-like cells. Our results indicated the shrinkage of fat droplets in reprogrammed mouse adipocytes and their transformation into spindle-shaped dermal fibroblasts. Reduced expression of PPAR-2, c/EBP, aP2, and leptin, the known markers of adipocytes, in RT-PCR, and enhanced expression of anti-ER-TR7, the known anti-fibroblast marker, in immunocytochemistry, were confirmed in the reprogrammed mouse adipocytes. The dermal fibroblast-like cells, reported here, may open up a new treatment mode for enabling early closure of deep burn wounds.

Hydrocortisone with fludrocortisone for septic shock: a systematic review and meta-analysis.

AIM: Combined hydrocortisone and fludrocortisone therapy for septic shock has not been evaluated with an independent systematic review. We aimed to elucidate the beneficial effects of a dual corticosteroid treatment regime involving both hydrocortisone and fludrocortisone for adult patients with septic shock on mortality. METHODS: We searched the Medline, Cochrane CENTRAL, and ICHUSHI databases for reports published before April 2019. We included randomized controlled trials that compared the use of both hydrocortisone and fludrocortisone with either corticosteroid-free or hydrocortisone-only treatments on adult patients with septic shock. Three researchers independently reviewed the studies. The meta-analyses were undertaken to assess primary outcome (28-day mortality) and secondary outcomes (in-hospital mortality, long-term mortality, shock reversal, and adverse events). RESULTS: Among the four studies eligible for data synthesis, we included 2,050 patients from three studies for quantitative synthesis. All studies used similar regimens (hydrocortisone and fludrocortisone for 7 days without tapering). The 28-day mortality rate was reduced after dual corticosteroid treatment (risk ratio, 0.88; 95% confidence intervals [CI], 0.78-0.99). The heterogeneity between the studies was low (I 2 = 0%). Patients who underwent dual corticosteroid treatment had lower long-term mortality rates (risk ratio, 0.90; 95% CI, 0.83-0.98) and higher rate of shock reversal after 28 days (odds ratio, 1.06; 95% CI, 1.01-1.12) than control patients. Adverse events (except for hyperglycemia) were similar among the treatment groups. CONCLUSIONS: The available evidence suggests that a combination of fludrocortisone and hydrocortisone is more effective than adjunctive therapy and could be recommended for septic shock.

Length of hospital stay and mortality associated with burns from assault: a retrospective study with inverse probability weighting analysis.

BACKGROUND: Burns resulting from assaults account for considerable morbidity and mortality among patients with burn injuries around the world. However, it is still unclear whether unfavorable clinical outcomes are associated primarily with the severity of the injuries. To elucidate the direct relationship between burns resulting from assaults and mortality and/or length of hospital stays, we performed this study with the hypothesis that burns from assault would be independently associated with fewer hospital-free days than would burns from other causes, regardless of the severity of burn injuries. METHODS: We conducted a retrospective cohort study, using a city-wide burn registry (1996-2017) accounting for 14 burn centers in Tokyo, Japan. Patients who arrived within 24 hours after injury were included, and those with self-inflicted burn injuries were excluded. Patients were divided into two groups according to mechanism of burns (assault vs. accident), and the number of hospital-free days until day 30 after injury (a composite of in-hospital death and hospital length of stay) was compared between the groups. To estimate the probability that an injury would be classified as an assault, we calculated propensity scores, using multivariate logistic regression analyses adjusted for known outcome predictors. We also performed an inverse probability weighting (IPW) analysis to compare adjusted numbers of hospital-free days. RESULTS: Of 7419 patients in the registry with burn injuries during the study period, 5119 patients were included in this study. Of these, 113 (2.2%) were injured as a result of assault; they had significantly fewer hospital-free days than did those with burns caused by accident (18 [27] vs. 24 [20] days; coefficient = [Formula: see text]3.4 [[Formula: see text]5.5 to [Formula: see text]1.3] days; p = 0.001). IPW analyses similarly revealed the independent association between assault burn injury and fewer hospital-free days (adjusted coefficient = [Formula: see text]0.6 [[Formula: see text]1.0 to [Formula: see text]0.1] days; p = 0.009). CONCLUSIONS: Burn from assault was independently associated with fewer hospital-free days, regardless of the severity of burn injuries. The pathophysiological mechanism underlying the relationship should be further studied in a prospective observational study.