This study tested the hypothesis that excessive tumor necrosis factor-alpha (TNF-alpha) levels in chronic venous leg ulcers are associated with impaired healing. TNF-alpha was measured by two enzyme-linked immunosorbent assays and a bioassay (KYM-1D4) in paired wound fluid samples collected during the nonhealing and healing phases from 21 human patients with venous leg ulcers. Soluble TNF receptor levels (p55 and p75) were also measured. The levels of immunoreactive TNF-alpha were significantly higher in wound fluid from nonhealing ulcers than in wound fluid from healing ulcers (p < 0.005), whereas the levels of bioactive TNF-alpha were not. Statistical analysis confirmed that TNF-alpha bioactivity relative to the amount of immunoreactive TNF-alpha was downregulated in wound fluid from nonhealing ulcers compared with healing ulcers. The levels of soluble p55 and p75 receptors in wound fluid showed a significant linear correlation (p < 0.001), suggesting a partially coordinated or common regulatory mechanism for the cleavage of transmembrane TNF receptors in chronic venous ulcers in vivo. Although the levels of soluble p75 receptors were significantly higher in nonhealing wound fluid compared with healing wound fluid (p < 0.025), these levels were theoretically inadequate to substantially neutralize the bioactivity of the accompanying TNF-alpha levels on their own. The bioactivity accompanying the elevated levels of immunoreactive TNF-alpha in wound fluid from nonhealing ulcers may have been further down-modulated by an additional mechanism. Because healing was initiated without a significant decline in the level of bioactive TNF-alpha, TNF-alpha-mediated events may not be the key events contributing to the impaired healing seen in chronic venous ulcers.

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BackgroundThere is a lack of rigorous research investigating the factors that influence scar outcome in children. Improved clinical decision-making to reduce the health burden due to post-burn scarring in children will be guided by evidence on risk factors and risk stratification. This study aimed to examine the association between selected patient, injury and clinical factors and the development of raised scar after burn injury. Novel patient factors were investigated including selected immunological co-morbidities (asthma, eczema and diabetes type 1 and type 2) and skin pigmentation (Fitzpatrick skin type).MethodsA prospective case-control study was conducted among 186 children who sustained a burn injury in Western Australia. Logistic regression was used to explore the relationship between explanatory variables and a defined outcome measure: scar height measured by a modified Vancouver Scar Scale (mVSS).ResultsThe overall correct prediction rate of the model was 80.6%; 80.9% for children with raised scars (>1 mm) and 80.4% for children without raised scars (≤1 mm). After adjustment for other variables, each 1% increase in % total body surface area (%TBSA) of burn increased the odds of raised scar by 15.8% (95% CI = 4.4–28.5%). Raised scar was also predicted by time to healing of longer than 14 days (OR = 11.621; 95% CI = 3.727–36.234) and multiple surgical procedures (OR = 11.521; 1.994–66.566).ConclusionsGreater burn surface area, time to healing of longer than 14 days, and multiple operations are independently associated with raised scar in children after burn injury. Scar prevention strategies should be targeted to children with these risk factors.