High Transepidermal Water Loss at the Closed Wound Site Marks Compromised Functional Wound Closure and Associates with Wound Recurrence in Diabetic Foot Ulcers: A Prognostic Factor Study

<b>Objective:</b> Wound closure is skin reepithelialization confirmed at two consecutive clinical visits 2 weeks apart. Our objective was to identify participant characteristics, including transepidermal water loss (TEWL), associated with complete wound closure of diabetic foot ulcers (DFUs) and reopening of a DFU within 2 weeks after initial closure in the National Institute of Diabetes and Digestive and Kidney Diseases-sponsored Diabetic Foot Consortium TEWL prospective observational cohort study of wound recurrence. At the site of wound closure, TEWL measures restoration of skin barrier function and functional wound closure. <b>Approach:</b> Four hundred and sixty-six eligible participants had physician-assessed wound closure at baseline. Of which, 418 (90%) had confirmed closure 2 weeks later and remained in the study, whereas 29 had their DFU reopen 2 weeks later and were not eligible for follow-up (<i>i.e.,</i> screen failures). We compared baseline characteristics of 418 enrolled and 29 screen fail individuals using Wilcoxon rank sum and Fisher's exact tests <i>p</i> value for continuous and categorical outcomes, respectively. <b>Results:</b> There were no statistically significant differences in demographics, including age, sex, race, education, employment status, social support, or dressing change requirements between groups. The failure to maintain closure group had longer median duration of index DFU before initial closure (25.8 vs. 14 weeks, <i>p</i> = 0.003), higher frequency of prior total contact casting use (37% vs. 14%, <i>p</i> = 0.003), and a higher median initial TEWL measurement at the healed ulcer midpoint (27.1 vs. 21.0 g/m^2/h, <i>p</i> = 0.006). <b>Innovation:</b> TEWL measurement at the site of wound closure can assess functional capacity of the skin in conjunction with current standards of wound closure end point in DFU and has significant potential to add quantitative measurement to assist in clinical assessment of healing wounds. <b>Conclusion:</b> Individuals with DFU who did not maintain wound closure had higher TEWL values at baseline, longer DFU wound duration, and more prior off-loading use. These findings are clinically relevant as a higher TEWL measurement demonstrates incomplete functional wound closure, supporting the use of TEWL to identify a healed DFU.