Materials and Methods
This study was a single-center, randomized controlled trial with 2 parallel groups. Eligible patients were randomized to either the UTSG group or conventional dressing group using a computerized randomization method.
Research Ethics Approval
This trial received approval from the Institutional Ethical Committee and was registered at the Clinical Trials Registry-India. No.REF/2020/05/033393.
Participants were recruited at the hospital on an outpatient basis.
Patients referred by general surgeons for nonhealing DFUs were eligible for the study. Before enrollment, patients were screened for inclusion in the trial, and a patient information sheet was provided. This process included explaining the aims of skin grafting, methods of skin grafting and subsequent wound management, anticipated benefits, and potential hazards of the study. Patients were afforded sufficient time (≥ 24 hours) to consider whether they wished to participate. Patients were then invited to participate in the study, and informed consent was obtained. Treatment occurred within 7 days of patient enrollment. Patients were eligible for inclusion if they had an acute DFU of less than 3 months and could participate in the trial and adhere to the requirements, including weekly visits and the follow-up regimen. Patients were excluded if they had any of the following: chronic wounds of more than 3 months' duration; Wagner grade III or IV DFUs; prior treatment with hyperbaric oxygen, NPWT, or growth factor application; and peripheral vascular disease (PVD) requiring vascular surgery intervention.
Clinical examination was routine, including obtaining a foot radiograph and a wound culture swab preoperatively. All wounds were assessed clinically, and wound size and quantity of granulation tissue were calculated using Mobile Wound Analyzer software (HealthPath) based on photographic images taken by a single camera for all cases. The Pressure Ulcer Scale for Healing (PUSH) tool was used to assess wound severity.
Routine lower limb palpation was carried out to look for dorsalis pedis artery, anterior tibial artery, and posterior tibial artery pulsations; cases with feeble or absent pulsation were advised to receive arterial Doppler to look for PVD. Patients with absent or monophasic Doppler flow requiring urgent vascular surgical intervention were excluded from the study. Patients with adequate flow and for whom a vascular surgeon advised conservative treatment were included in the study. Patients in the test group underwent debridement and UTSG in a single session.
Prior to grafting, the wound was debrided, necrotic patch and slough were excised, the wound edge was freshened, and thorough saline irrigation was performed. In addition to the wound being completely debrided, thorough irrigation was performed after complete hemostasis had been achieved.
As is typical, the graft was taken from the opposite thigh. The donor site was cleaned, prepped, and draped. Saline was injected into the subepidermal plane using a 10-mL syringe to separate the superficial epidermis and deeper dermis. The amount of saline injected depends the graft size required. Emollient liquid paraffin was applied on the top to facilitate easy gliding of the blade. The Watson modification of the Humby knife with the lowest blade setting was used for graft harvesting (Figure 5). To confirm the UTSG, the ultrathin graft was macroscopically identified by its transparent nature and punctuated minor bleed at the donor site (Figure 6). The graft was applied over the wound and fixed with multiple staples to ensure contact between the graft and the wound bed. The wound was dressed with petrolatum gauze, followed by applying a nonadherent soft pad with a soft cloth backing. An 8-layer plaster of Paris slab was used to immobilize the ankle joint. The donor site was covered with petrolatum gauze, and a tight compression dressing was applied. The wound dressing was first opened on postoperative day 5 and subsequently as required (usually every third day). Staples were removed after 10 to 14 days.
Wound bed Biopsy
Incisional tissue biopsy at the center of the wound bed was performed before grafting and 3 weeks after grafting. Biopsy prior to grafting was done under spinal anesthesia, and a repeat biopsy was performed at week 3 after grafting following administration of adequate local anesthesia (2% lidocaine). The specimens were placed in a sterile vial containing 4% formaldehyde and transferred to the laboratory for histopathologic examination.
The control group underwent initial debridement and multiple regular saline-gauze dressings. Local debridement of slough on an outpatient basis was done at each visit if required. Patients were observed for progression to abscess or osteomyelitis, and the presence of either resulted in immediate debridement or amputation.
The primary endpoints were complete healing of the wound after grafting or completion of the study period (12 weeks). Secondary endpoints included wound-related adverse events (eg, progression of infection) leading to interventions such as amputation during the study period.
Wound healing was assessed clinically, with wound measurement recorded using the wound analysis software at each visit (Figure 7). High-quality, accurate, standardized images for digital measurement of the wound surface area were obtained and stored in the digital photograph diary.
Study outcomes measured were time to wound healing, total number of hospital visits and cost of treatment, final outcome of the wound, and the incidence of adverse events occurring within the duration of the study. Furthermore, the authors determined the wound-healing mechanism of UTSG by analyzing histopathologic reports of the wound bed tissue biopsy to assess improved granulation tissue and vascularity of the wound bed (Figure 8).
The study was opened to recruitment in January 2017 and closed in September 2019. Each patient was to receive weekly follow-up visits for 12 weeks or until wound healing occurred. The final review was to occur at the end of the third month following treatment initiation (ie, at the last hospital visit).
The present pilot study was given a significance level of .05 for 80% power, yielding a sample size of 26 patients per group. The goal was to recruit a total of 52 patients into the study.
Randomization, Allocation Concealment, and Blinding
Once consent was obtained, patients were randomly assigned to either the test group or the control group. A random allocation sequence was computer generated using SPSS Statistics for Windows, version 22.0 (IBM Corporation). The allocation sequence was sealed in identical opaque envelopes and given to the enrolling researcher upon receipt of patient consent.
The surgical team, clinical staff, and patients were not blinded to the intervention status. Independent blinded analysis of the photographic diary was carried out by 2 plastic surgeons (other than the operating surgeon); they were blinded to the intervention and study groups. Outcome parameters were recorded as per their inference.
All data collected were recorded on paper forms and in a digital folder. The surgical team and trial personnel collected data. A research fellow ensured the accuracy of the data collection by performing sample assessments at regular intervals. Any adverse events were recorded and reported to the primary investigators as well as the institutional ethics committee. Wounds were assessed and recorded in a wound assessment form at each visit. The wound analysis software applied to photographic images was used to measure the wound surface area digitally. The number and cost of outpatient visits were recorded, and the type and cost of the dressings used were documented.
Calculation of the total cost of treatment included the cost of hospitalization as well as the procedure charge and dressing charges at each subsequent hospital visit.
Descriptive and inferential statistical analysis was performed in the current study. Results of continuous measurements are presented as the mean, and the results of categorical measurements are presented as n (%). A P value less than .05 was considered statistically significant. The following assumptions about data were made: (1) dependent variables should be normally distributed, (2) samples drawn from the population should be random, and (3) cases of the samples should be independent.
The Student t test (2-tailed, independent) was used to calculate the significance of study parameters on a continuous scale between 2 groups (intergroup analysis) on metric parameters. Either the χ 2 test or the Fisher exact test was used to calculate the significance of study parameters on a categorical scale between 2 or more groups; nonparametric setting was used for qualitative data analysis. The Fisher exact test is used when cell samples are very small.
Statistical analysis was performed using SPSS Windows, version 18.0 (IBM Corporation) and R version 3.2.2 (Bell Laboratories). Word and Excel (Microsoft) were used to generate graphs and tables.
Patients who received the study treatment were evaluated for analysis. If the clinical course could not be fully evaluated, the date of the last visit was considered to be the final data point for analysis. Baseline characteristics of the 2 groups were recorded. Mean time to wound healing was determined based on the number of weeks until complete reepithelialization.
Wounds. 2022;34(2):57-67. © 2022 HMP Communications, LLC