Assessment and determinants of global outcomes among 445 mass-casualty burn survivors: A 2-year retrospective cohort study in Taiwan.

PURPOSE: To study outcomes among survivors of the mass-casualty powder explosion on 27 June 2015, at Formosa Fun Coast Waterpark, New Taipei City, Taiwan. METHODS: Using retrospective data on Taiwanese survivors, we analyzed prehospital management, burns assessment and prognosis, functional recovery, and medical costs, followed-up through 30 June 2017. We related outcomes to burn extent, categorized according to the percentages of total body surface area with second/third-degree burns (%TBSA) or autologous split-thickness skin grafts (%STSG), and an investigational scale: f{SASG} = (%TBSA + %STSG)/2, stratified by %STSG. Analyses included casualty dispersal, comparisons between %TBSA, %STSG and f{SASG}, and their relationships with length of hospitalization, times to rehabilitation and social/school re-entry, physical/mental disability, and medical costs. We also investigated how burn scars restricting joint mobility affected rehabilitation duration. RESULTS: 445 hospitalized casualties (excluding 16 foreigners, 23 with 0% TBSA and 15 fatalities) aged 12-38 years, had mean TBSA of 41.1%. Hospitalization and functional recovery durations correlated with %TBSA, %STSG and f{SASG} - mean length of stay per %TBSA was 1.5 days; more numerous burn scar contractures prolonged rehabilitation. Females had worse burns than males, longer hospitalization and rehabilitation, and later school/social re-entry; at follow-up, 62.3% versus 37.7% had disabilities and 57.7% versus 42.3% suffered mental trauma (all p ≤ 0.001). Disabilities affecting 225/227 people were skin-related; 34 were severely disabled but 193 had mild/moderate impairments. The prevalence of stress-related and mood disorders increased with burn extent. Treatment costs (mean USD-equivalents ∼$48,977/patient, ∼$1192/%TBSA) increased with burn severity; however, the highest %TBSA, %STSG and f{SASG} categories accounted for <10% of total costs, whereas TBSA 41-80% accounted for 73.2%. CONCLUSIONS: Besides %TBSA, skin-graft requirements and burn scar contractures are complementary determinants of medium/long-term outcomes. We recommend further elucidation of factors that influence burn survivors' recovery, long-term physical and mental well-being, and quality of life.

Involvement of PI3K and ROCK signaling pathways in migration of bone marrow-derived mesenchymal stem cells through human brain microvascular endothelial cell monolayers.

Bone marrow-derived mesenchymal stem cells (MSC) represent an important and easily available source of stem cells for potential therapeutic use in neurological diseases. The entry of circulating cells into the central nervous system by intravenous administration requires, firstly, the passage of the cells across the blood-brain barrier (BBB). However, little is known of the details of MSC transmigration across the BBB. In the present study, we employed an in vitro BBB model constructed using a human brain microvascular endothelial cell monolayer to study the mechanism underlying MSC transendothelial migration. Transmigration assays, transendothelial electrical resistance (TEER) and horseradish peroxidase (HRP) flux assays showed that MSC could transmigrate through human brain microvascular endothelial cell monolayers by a paracellular pathway. Cell fractionation and immunofluorescence assays confirmed the disruption of tight junctions. Inhibition assays showed that a Rho-kinase (ROCK) inhibitor (Y27632) effectively promoted MSC transendothelial migration; conversely, a PI3K inhibitor (LY294002) blocked MSC transendothelial migration. Interestingly, adenovirus-mediated interference with ROCK in MSC significantly increased MSC transendothelial migration, and overexpression of a PI3K dominant negative mutant in MSC cells could block transendothelial migration. Our findings provide clear evidence that the PI3K and ROCK pathways are involved in MSC migration through human brain microvascular endothelial cell monolayers. The information yielded by this study may be helpful in constructing gene-modified mesenchymal stem cells that are able to penetrate the BBB effectively for cell therapy.