Dehydrated human amnion/chorion membrane treatment of venous leg ulcers: correlation between 4-week and 24-week outcomes.

OBJECTIVE: To evaluate correct correlation between an intermediate rate of wound reduction (40% wound area reduction after 4-weeks treatment) and complete healing at 24 weeks in patients with a venous leg ulcer (VLU). METHOD: A retrospective follow-up study of patients completing a multicenter randomised controlled trial (RCT) comparing the number of patients achieving at least 40% healing of their VLU within 4-weeks of treatment with either dehydrated human amnion/chorion membrane (dHACM) allograft or multilayer compression only was conducted. Outcomes assessed were rates of complete healing within 24 weeks of enrolment and days to healing. Data were divided into two groups based on status at RCT completion (healed at least 40% yes or no). Correct correlation with status at 4 weeks and complete healing within 24 weeks was determined. Clinical characteristics were also compared for patients with and without correct correlation between 4-week and 24-week status. RESULTS: We identified 55 patients at 5 study sites. Some 47 without complete healing during the initial study were eligible. As three patients were lost to follow-up we evaluated 44 records. Of these, 20 (45.4%) had reduced wound size of ≥40% and 24 (55%) had <40% reduction during the initial study. Complete healing occurred in 16/20 (80%) of the ≥40% group at a mean of 46 days, p=0.0027 and 8/24 (33.3%) of the <40% group at a mean of 103.6 days, p=0.0023. Overall, correct correlation of status at 4 weeks and ultimate healing status of VLU occurred in 32/44 patients (73%). CONCLUSION: These results confirm that the intermediate outcome used in our initial study is a viable predictor of ultimate VLU healing.

Abnormal connexin expression in human chronic wounds.

BACKGROUND: Regulated alteration of connexin expression has been shown to be integral to acute wound repair. Downregulation of the gap-junction protein connexin 43 at the wound edge has been correlated with keratinocyte and fibroblast migration, while abnormal overexpression of connexin 43 significantly perturbs healing, as shown in the streptozotocin diabetic rodent impaired healing model. OBJECTIVES: To examine the protein expression levels of connexin 43, in addition to connexins 26 and 30, in a variety of human chronic wounds. METHODS: Wound-edge punch biopsies and a matched control from the arm were taken from a cohort of patients with venous leg, diabetic foot or pressure ulcers. Wound connexin expression in each patient was compared with that in a matched, nonwounded arm punch. Tissue was sectioned, stained and imaged by confocal microscopy using identical parameters per patient to permit quantification. RESULTS: Epidermal connexin 43, connexin 26 and connexin 30, and dermal connexin 43 were discovered to be strikingly upregulated in every ulcer from all three wound types, pointing to connexin upregulation as a common feature between chronic wounds. CONCLUSIONS: This result supports efforts to target connexin 43 to promote cell migration and wound healing in chronic ulcers.