Improved healing of chronic diabetic foot wounds in a prospective randomised controlled multi‐centre clinical trial with a microvascular tissue allograft

This study assesses the impact of a processed microvascular tissue (PMVT) allograft on wound closure and healing in a prospective, single‐blinded, multi‐centre, randomised controlled clinical trial of 100 subjects with Wagner Grade 1 and 2 chronic neuropathic diabetic foot ulcerations. In addition to standard wound care, including standardised offloading, the treatment arm received PMVT while the control arm received a collagen alginate dressing. The primary endpoint was complete wound closure at 12 weeks. Secondary endpoints assessed on all subjects were percent wound area reduction, time to healing, and local neuropathy. Novel exploratory sub‐studies were conducted for wound area perfusion and changes in regional neuropathy. Weekly application of PMVT resulted in increased complete wound closure at 12 weeks (74% vs 38%; P = .0003), greater percent wound area reduction from weeks four through 12 (76% vs 24%; P = .009), decreased time to healing (54 days vs 64 days; P = .009), and improved local neuropathy (118% vs 11%; P = .028) compared with the control arm. Enhanced perfusion and improved regional neuropathy were demonstrated in the sub‐studies. In conclusion, this study demonstrated increased complete healing with PMVT and supports its use in treating non‐healing DFUs. The observed benefit of PMVT on the exploratory regional neuropathy and perfusion endpoints warrants further study.     

Multi‐centre prospective randomised controlled clinical trial to evaluate a bioactive split thickness skin allograft vs standard of care in the treatment of diabetic foot ulcers

Diabetic foot ulcers (DFUs) pose a significant risk for infection and limb loss. Advanced wound therapies including human skin allografts have shown promise in resolving these challenging wounds. The primary objective of this randomised, prospective study was to compare the response of 100 subjects with non‐healing DFUs of which 50 were treated with a cryopreserved bioactive split thickness skin allograft (BSA) (TheraSkin; Misonix,Inc., Farmingdale, NY) compared with 50 subjects treated with standard of care (SOC, collagen alginate dressing) at 12 weeks. Both groups received standardised care that included glucose monitoring, weekly debridement''s as appropriate, and an offloading device. The primary endpoint was proportion of full‐thickness wounds healed at 12 weeks, with secondary endpoints including differences in percent area reduction (PAR) at 12 weeks, changes in Semmes‐Weinstein monofilament score, VAS pain, and w‐QoL. The result illustrated in the intent‐to‐treat analysis at 12 weeks showed that 76% (38/50) of the BSA‐treated DFUs healed compared with 36% (18/50) treated with SOC alone (adjusted P = .00056). Mean PAR at 12 weeks was 77.8% in the BSA group compared with 49.6% in the SOC group (adjusted P = .0019). In conclusion, adding BSA to SOC appeared to significantly improve wound healing with a lower incidence of adverse events related to treatment compared with SOC alone.     

Fat grafting and platelet‐rich plasma for the treatment of diabetic foot ulcers: A feasibility‐randomised controlled trial

Chronic, nonhealing diabetic foot ulcers (DFU) are increasing in prevalence and are often unresponsive to conventional therapy. Adipose tissue, containing adipose‐derived stem cells, and platelet rich plasma (PRP) are regenerative therapies rich in growth factors which may provide a solution to chronic wound healing. This study aimed to assess the feasibility of conducting a definitive randomised controlled trial (RCT) to investigate the efficacy of these therapies for the treatment of DFU. This was a single centre, feasibility, three‐arm, parallel group RCT. Eligible DFU patients were randomised on a 1:1:1 basis to three intervention arms: control (podiatry); fat grafting; fat grafting with PRP. The intervention was delivered once and patients were followed‐up for 12 weeks. The primary objective was to assess measures of trial feasibility. Clinical outcomes and health‐related quality of life (HRQoL) were also evaluated. Three hundred and thirty four patients were screened and 32 patients (9.6%) were deemed eligible with 18 enrolled in the trial (6 per arm) over 17 months. All participants completed the trial with no withdrawals or crossover. Participant engagement was high with most HRQoL questionnaires returned and only 4.8% follow‐up appointments missed. There were five adverse events (AEs) related to the trial with no serious AEs. Five (28%) of the wounds healed. There was no difference between any of the groups in terms of clinical outcomes. This feasibility study demonstrated that a multi‐centre RCT is safe and feasible with excellent patient engagement. We have highlighted crucial information regarding methodology and recruitment, which will guide future trial design. Registration number: {"type":"clinical-trial","attrs":{"text":"NCT03085550","term_id":"NCT03085550"}}NCT03085550 clinicaltrials.gov. Registered 01/03/2017.     

Complete wound closure following a single topical application of a novel autologous homologous skin construct: first evaluation in an open‐label,single‐arm feasibility study in diabetic foot ulcers

Diabetic foot ulcers (DFUs) are a growing burden on patients and health care systems that often require multiple treatments of both conventional and advanced modalities to achieve complete wound closure. A novel autologous homologous skin construct (AHSC) has been developed to treat cutaneous defects with a single topical application, by leveraging the endogenous repair capabilities of the patient's healthy skin. The AHSC's ability to close DFUs with a single treatment was evaluated in an open‐label, single‐arm feasibility study. Eleven patients with DFUs extending up to tendon, bone, or capsule received a single topical application of AHSC. Closure was documented weekly with high‐resolution digital photography and wound planimetry. All 11 DFUs demonstrated successful graft take. Ten DFUs closed within 8 weeks. The median time‐to‐complete closure was 25 days. The mean percent area reduction for all 11 wounds at 4 weeks was 83%. There were no adverse events related to the AHSC treatment site. This pilot study demonstrated AHSC may be a viable single application topical intervention for DFUs and warrants investigation in larger, controlled studies.     

The effectiveness of a new dried human amnion derived membrane in addition to standard care in treating diabetic foot ulcers: A patient and assessor blind,randomised controlled pilot study

Recent reviews suggest that amniotic membrane products may accelerate healing of diabetic foot ulcers. A new dried human amniotic membrane (dHAM) has been used for ocular ulcers but not for diabetic foot ulcers. This was a multi‐centre, prospective, patient and observer blind, randomised controlled pilot trial, to investigate whether 2 weekly addition of the dHAM to standard care versus standard care alone increased the proportion of healed participants'' index foot ulcers within 12 weeks. Thirty‐one people (mean age 59.8 years, 81% male, 87% type 2 diabetes) were randomised (15 dHAM, 16 usual care). Within 12 weeks, healing occurred in 4 (27%) ulcers in the dHAM group versus 1 (6.3%) usual care group (P = .1). Percentage wound area reduction was higher in the dHAM versus control group. (P = .0057). There was no difference in AEs between the two groups. Six participants allocated to dHAM correctly identified their treatment group, although 5 in usual care incorrectly thought they were in the intervention arm. This pilot trial result is encouraging showing that this dHAM preparation is safe and promising treatment. These results will be used to design a statistically powered, definitive double blind randomised controlled trial.     

Extracorporeal shockwave therapy compared with standard care for diabetic foot ulcer healing: An updated systematic review

Emerging evidence suggests that extracorporeal shockwave therapy (ESWT) may improve time to DFU healing. The aim of this review was to appraise the evidence on role of ESWT in DFU healing and impact of different ESWT doses. Databases were searched for trials comparing ESWT plus standard care to standard care alone in participants with DFUs. Search results were reviewed by two independent reviewers. The Cochrane Risk of Bias 2 tool and GRADE approach was used to assess bias and certainty. The primary outcome was time to healing. The search identified 345 papers after duplicates removed. Six trials consisting of 471 participants were included. There was unclear or high risk of bias across all domains. Time to ulcer healing was probably shorter in patients treated with ESWT compared with standard ulcer care alone (GRADE: low certainty). Patients treated with ESWT were more likely to heal at 20 weeks post-ESWT compared with those treated with standard ulcer care alone (GRADE: low certainty). There was significant heterogeneity. ESWT remains a promising new treatment but the translation into routine clinical practice is still limited by the low certainty of evidence surrounding its effectiveness, case selection and optimum dose.     

A multi‐centre,single‐blinded randomised controlled clinical trial evaluating the effect of resorbable glass fibre matrix in the treatment of diabetic foot ulcers

Diabetic foot ulcers (DFUs) are at risk for detrimental complications even with current, standard of care (SOC) treatments. The primary objective of this randomised controlled trial was to compare a unique resorbable glass microfiber matrix (Mirragen; Advanced Wound Matrix [BBGFM]; ETS Wound Care, Rolla, Missouri) compared with a standard of care group (SOC, collagen alginate dressing) at 12 weeks. Both groups received standard diabetic foot care including glucose monitoring, weekly debridements when needed and an offloading device. The primary endpoint was proportion of full‐thickness, non‐infected, non‐ischaemic wounds healed at 12 weeks, with secondary endpoints including percent area reduction (PAR) and changes in Semmes‐Weinstein monofilament testing. The result illustrated in the intent‐to‐treat analysis at 12 weeks showed that 70% (14/20) of the BBGFM‐treated DFUs healed compared with 25% (5/20) treated with SOC alone (adjusted P = .006). Mean PAR at 12 weeks was 79% in the BBGFM group compared with 37% in the SOC group (adjusted P = .027). Mean change in neuropathic score between baseline and up to 12 weeks of treatment was 2.0 in the BBGFM group compared with −0.6 in the SOC group where positive improvement in scores are better (adjusted P = .008). The mean number of BBGFM applications was 6.0. In conclusion, adding BBGFM to SOC significantly improved wound healing with no adverse events related to treatment compared with SOC alone.     

A multicentre,randomised controlled clinical trial evaluating the effects of a novel autologous,heterogeneous skin construct in the treatment of Wagner one diabetic foot ulcers: Interim analysis

We desired to carefully evaluate a novel autologous heterogeneous skin construct in a prospective randomised clinical trial comparing this to a standard-of-care treatment in diabetic foot ulcers (DFUs). This study reports the interim analysis after the first half of the subjects have been analysed. Fifty patients (25 per group) with Wagner 1 ulcers were enrolled at 13 wound centres in the United States. Twenty-three subjects underwent the autologous heterogeneous skin construct harvest and application procedure once; two subjects required two applications due to loss of the first application. The primary endpoint was the proportion of wounds closed at 12 weeks. There were significantly more wounds closed in the treatment group (18/25; 72%) vs controls (8/25; 32%) at 12 weeks. The treatment group achieved significantly greater percent area reduction compared to the control group at every prespecified timepoint of 4, 6, 8, and 12 weeks. Thirty-eight adverse events occurred in 11 subjects (44%) in the treatment group vs 48 in 14 controls (56%), 6 of which required study removal. In the treatment group, there were no serious adverse events related to the index ulcer. Two adverse events (index ulcer cellulitis and bleeding) were possibly related to the autologous heterogeneous skin construct. Data from this planned interim analysis support that application of autologous heterogeneous skin construct may be potentially effective therapy for DFUs and provide supportive data to complete the planned study.     

Use of a purified reconstituted bilayer matrix in the management of chronic diabetic foot ulcers improves patient outcomes vs standard of care: Results of a prospective randomised controlled multi‐centre clinical trial

Diabetic foot infections continue to be a major challenge for health care delivery systems. Following encouraging results from a pilot study using a novel purified reconstituted bilayer matrix (PRBM) to treat chronic diabetic foot ulcers (DFUs), we designed a prospective, multi‐centre randomised trial comparing outcomes of PRBM at 12 weeks compared with a standard of care (SOC) using a collagen alginate dressing. The primary endpoint was percentage of wounds closed after 12 weeks. Secondary outcomes included assessments of complications, healing time, quality of life, and cost to closure. Forty patients were included in an intent‐to‐treat (ITT) and per‐protocol (PP) analysis, with 39 completing the study protocol (n = 19 PRBM, n = 20 SOC). Wounds treated with PRBM were significantly more likely to close than wounds treated with SOC (ITT: 85% vs 30%, P = .0004, PP: 94% vs 30% P = .00008), healed significantly faster (mean 37 days vs 67 days for SOC, P = .002), and achieved a mean wound area reduction within 12 weeks of 96% vs 8.9% for SOC. No adverse events (AEs) directly related to PRBM treatment were reported. Mean PRBM cost of healing was $1731. Use of PRBM was safe and effective for treatment of chronic DFUs.     

A single arm prospective feasibility study evaluating wound closure with a unique wearable device that provides intermittent plantar compression and offloading in the treatment of non‐healing diabetic foot ulcers

The incidence and economic burden of diabetic foot ulcers continues to rise throughout the world. In this prospective study, a unique device designed to offload the wound, enhance circulation and monitor patient compliance was evaluated for safety and efficacy. The device provides offloading and intermittent plantar compression to improve the pedal flow of oxygenated blood and support wound healing while recording patient use. Ten patients with non‐healing diabetic foot ulcers UTgrade 1A/Wagner grade 1 were treated weekly for up to 12 weeks. The primary endpoint was complete wound closure at 12 weeks, and secondary endpoints included healing time, percent area reduction and changes in pain using the visual analogue pain scale. Eight out of ten wounds healed within 12 weeks(80%), and the mean healing time was 41 days(95% CI:24.3–58.3). The percent area reduction was 75(SD:53.9). The baseline visual analogue pain scale was 4.5(2.9) as compared with 3.3(3.4) at end of study. No device‐related or serious adverse events were reported. This unique intermediate plantar compression and offloading device may be considered as an alternative for safe and effective for treatment of non‐healing diabetic foot ulcers. During treatment, wound healing was significantly accelerated, and pain was improved. Larger randomised controlled trials are underway to validate these early findings.     

Outcome predictors for wound healing in patients with a diabetic foot ulcer

The aim of this study was to identify diabetic foot ulcer (DFU) patients at risk for the development of a hard‐to‐heal wound. This is a post‐hoc analysis of a prospective cohort study including a total of 208 patients with a DFU. The primary endpoints were time to healing and the development of a hard‐to‐heal‐wound. Univariable and multivariable logistic and Cox regression analysis were used to study the associations of patient characteristics with the primary endpoints. The number of previous DFUs [odds ratio (OR): 1.42, 95% confidence interval (CI): 1.01‐1.99, P = .04], University of Texas (UT) classification grade 2 (OR: 2.93, 95% CI: 1.27‐6.72, P = .01), UT classification grade 3 (OR: 2.80, 95% CI: 1.17‐6.71, P = .02), and a diagnosis of foot stand deformation (OR: 1.54, 95% CI: 0.77‐3.08, P = .05) were significantly associated with the development of a hard‐to‐heal wound. Only UT classification grade 3 (HR: 0.61, 95% CI: 0.41‐0.90, P = .01) was associated with time to healing. The number of previous DFUs, UT classification grade, and a diagnosis of foot deformation are significantly associated with development of a hard‐to‐heal wound in patients with a DFU. The only predictor significantly associated with time to healing was UT classification grade 3. These patient characteristics can be used to identify patients at risk for the development of hard‐to‐heal wounds, who might need an early intervention to prevent wound problems.     

Preliminary investigation of topical nitroglycerin formulations containing natural wound healing agent in diabetes‐induced foot ulcer

Nitroglycerin (NTG) is an organic nitrate rapidly denitrated by enzymes to release free radical nitric oxide and shows improved wound healing and tissue protection from oxidative damage. The purpose of this study was to evaluate whether topical application of NTG in the form of gel/ointment along with a natural wound healing agent, aloe vera, would bring about wound healing by using diabetes‐induced foot ulcer model and rat excision wound model. All these formulations were evaluated for pH, viscosity, drug content and ex vivo diffusion studies using rat skin. Based on ex vivo permeation studies, the formulation consisting of carbopol 974p as a gelling agent and aloe vera was found to be suitable. The in vivo study used streptozotocin‐induced diabetic foot ulcer and rat excision wound models to analyse wound healing activity. The wound size in animals of all treated groups was significantly reduced compared with that of the diabetic control and marketed treated animals. This study showed that the gel formed with carbopol 974p (1%) and aloe vera promotes significant wound healing and closure in diabetic rats compared with the commercial product and provides a promising product to be used in diabetes‐induced foot ulcer.     

Use of an aseptically processed,dehydrated human amnion and chorion membrane improves likelihood and rate of healing in chronic diabetic foot ulcers: A prospective,randomised, multi‐centre clinical trial in 80 patients

Amnion and chorion allografts have shown great promise in healing diabetic foot ulcers (DFUs). Results from an interim analysis of 40 patients have demonstrated the accelerated healing ability of a novel aseptically processed, dehydrated human amnion and chorion allograft (dHACA). The goal of this study was to report on the full trial results of 80 patients where dHACA was compared with standard of care (SOC) in achieving wound closure in non‐healing DFUs. After a 2‐week screening period, during which patients with DFUs were unsuccessfully treated with SOC, patients were randomised to either SOC alone or SOC with dHACA applied weekly for up to 12 weeks. At 12 weeks, 85% (34/40) of the dHACA‐treated DFUs healed, compared with 33% (13/40) treated with SOC alone. Mean time to heal within 12 weeks was significantly faster for the dHACA‐ treated group compared with SOC, 37 days vs 67 days in the SOC group (P = .000006). Mean number of grafts used per healed wound during the same time period was 4.0, and mean cost of the tissue to heal a DFU was $1771. The authors concluded that aseptically processed dHACA heals DFUs significantly faster than SOC at 12 weeks.     

“When nothing happens,nobody is afraid!” beliefs and perceptions around self‐care and health‐seeking behaviours: Voices of patients living with diabetic lower extremity amputation in primary care

Self‐management and self‐care are the cornerstone of diabetes care and an essential part of successfully preventing or delaying diabetes complications. Yet, despite being armed with the required information and guidance for self‐management, self‐care and adherence to foot self‐care recommendations and compliance to medication among patients with diabetic foot ulcer and diabetic lower extremity amputations remain low and suboptimal. This study reveals in‐depth account of nine such patients'' beliefs and perceptions around their illness, their self‐care, and their health‐seeking behaviours. Patients living with diabetic lower extremity amputation displayed profound lack of knowledge of self‐care of diabetes and foot and passive health‐related behaviours. The overarching sense that "when nothing happens, nobody is afraid," points to a lack of motivation in taking charge of one''s own health, whether this is with reference to treatment or care adherence, following recommended self‐care advice, or seeking timely treatment. The Health Beliefs Model provides the theoretical framework for probing into the factors for the participants'' suboptimal self‐care and passive health‐seeking behaviours. Two themes emerged from data analysis: profound knowledge deficit and passive health‐related behaviours. The beliefs and perceptions around self‐care and health‐seeking behaviours for patients with lower extremity amputation are interpreted as the “ignorant self” with passive health‐seeking behaviours. Patients with diabetes and diabetic foot diseases may benefit from personalized education, motivational interviewing, and family support.     

Diabetic foot ulcer,the effect of resource‐poor environments on healing time and direct cost: A cohort study during Syrian crisis

Diabetic foot ulcer (DFU) is one of the slowest healing wounds that hurt the human body. Many studies from developed countries are concerned about materials, procedures, and equipment that accelerate the healing time. In Sweden, the diabetic foot management costs around 24965$/patient. In this review, we would evaluate the healing time of DFUs during what is considered one of the worst humanitarian crisis of the 21st century. 1747 DFUs were studied from the main diabetic foot clinic in Damascus (2014‐2019). We predicted many variables that could prolong the healing time. The cost according to these variables was also reported. The SINBAD Classification was performed to grade the severity of ulcers. We noticed that the median healing time for DFUs was 8 weeks. Almost half of these ulcers healed between 3 and 12 weeks. The time of healing for men was significantly longer than that for women. While the presence of infection doubled the median time of healing, the presence of peripheral artery disease doubled the mean of the direct health care cost. The location of the ulcer acted as another independent risk factor. In conclusion, DFUs face many barriers to heal during a crisis.The environment with resource‐poor settings should be added to the traditional risk factors that delay the healing of DFUs for months or even years. More studies from disaster are as are needed to evaluate low‐cost materials that could be cost effective in applying standard care of the diabetic foot.     

Histological analysis of fat grafting with platelet‐rich plasma for diabetic foot ulcers—A randomised controlled trial

Diabetic foot ulcers are often unresponsive to conventional therapy and are a leading cause of amputation. Animal studies have shown stem cells and growth factors can accelerate wound healing. Adipose‐derived stem cells are found in fat grafts and mixing them with platelet‐rich plasma (PRP) may improve graft survival. This study aimed to establish the histological changes when diabetic foot ulcers are treated with fat grafts and PRP. A three‐armed RCT was undertaken of 18 diabetic foot ulcer patients: fat grafting; fat grafting with PRP; and routine podiatry care. Biopsies were obtained at week 0, 1, and 4, and underwent quantitative histology/immunohistochemistry (H&E, CD31, and Ki67). Treatment with fat and PRP increased mean microvessel density at 1 week to 1645 (SD 96) microvessels/mm² (+32%‐45% to other arms, P = .035). PRP appeared to increase vascularity surrounding fat grafts, and histology suggested PRP may enhance fat graft survival. There was no clinical difference between arms. This study demonstrates PRP with fat grafts increased neovascularisation and graft survival in diabetic foot ulcers. The histology was not, however, correlated with wound healing time. Future studies should consider using apoptosis markers and fluorescent labelling to ascertain if enhanced fat graft survival is due to proliferation or reduced apoptosis. Trial registration {"type":"clinical-trial","attrs":{"text":"NCT03085550","term_id":"NCT03085550"}}NCT03085550.     

Ulcer‐free survival days and ulcer healing in patients with diabetic foot ulcers: A prospective cohort study

Healing rates may not give a complete indication of the effectiveness and management of diabetic foot ulcers because of high recurrence rates. The most important outcome for patients is remaining ulcer‐free; however, this has hardly been investigated. The aim of our study was to prospectively investigate ulcer‐free survival days and ulcer healing in patients with diabetic foot ulcers. This was a prospective cohort study of all referrals to our diabetic foot expertise centre from December 2014 to April 2017. Outcomes were determined after a minimum follow‐up period of 12 months. Primary outcomes were ulcer‐free survival days and 12‐month healing percentages. Predictors for ulcer‐free survival days and healing were investigated in multivariate analyses. A total of 158 patients were included. Median ulcer‐free survival days in the healed group were 233 days (interquartile range [IQR] 121‐312) and 131 days (IQR 0–298) in the overall population. The healing rate at 12‐month follow up was 67% (106/158), and the recurrence rate was 31% (33/106). Independent predictors of ulcer‐free survival days were duration of diabetes, peripheral artery disease (PAD), cardiovascular disease, end‐stage renal disease (ESRD), and infection. Ulcer‐free survival days are related to PAD and cardiovascular disease, and ulcer‐free survival days should be the main outcome when comparing the effectiveness of management and prevention of the diabetic foot ulcers.     

The effect of low‐level laser therapy on diabetic foot ulcers: A meta‐analysis of randomised controlled trials

Our purpose was to perform a meta‐analysis to evaluate the effect of Low‐level laser therapy (LLLT) on diabetic foot ulcers (DFUs). The PubMed, Cochrane, Embase, Web of Science, Chinese BioMedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), VIP and Wanfang databases were searched systematically up to August 27, 2020. Studies that met the inclusion criteria were included in the analysis. A total of 13 randomised controlled trials (RCTs) and 413 patients were analysed. Compared with the control group, LLLT significantly increased the complete healing rate (risk ratio [RR] = 2.10, 95% confidence interval [CI] 1.56‐2.83, P < .00001), reduced the ulcer area (standardised mean difference [SMD] = 3.52, 95% CI 1.65‐5.38, P = .0002), and shortened the mean healing time (SMD = −1.40, 95% CI −1.90 to −0.91, P < .00001) of patients with DFUs. The quality of the evidence was very low according to the GRADE system. LLLT is a promising and effective adjuvant treatment to accelerate the healing of DFUs. Further evidence from larger samples and higher quality RCTs is needed to prove the effect of LLLT and to determine the most appropriate parameters for the healing of DFUs.     

The efficacy of topical royal jelly on healing of diabetic foot ulcers: a double‐blind placebo‐controlled clinical trial

Foot ulcers are major sources of morbidity in individuals with diabetes mellitus. As royal jelly (RJ, a worker honey bee product) contains enzymatic, antibacterial and vasodilative properties, it can potentially help in healing of diabetic foot ulcers (DFUs). This study aimed to evaluate the efficacy of topical RJ on healing of DFUs. Diabetic patients with foot ulcers who were referred to us at Khorshid Hospital, Isfahan, Iran, were managed by offloading, infection control, vascular improvement and debridement (if required). Then, all ulcers were randomly selected to receive either 5% sterile topical RJ or placebo on their total surface area. Patients were followed for 3 months or until complete healing. Twenty‐five patients (6 females and 19 males) and a total of 64 ulcers were included and randomly allocated to case or control group (32 per group). Four ulcers were excluded and 60 ulcers included in the final analysis. Healing parameters including depth, length and width reduction rate, duration of complete healing and incidence of complete healing did not show any significant difference (P = 0·69, 0·95, 0·7, 0·74 and 0·6, respectively) between groups. We did not observe any side effect of topical RJ application. This study could not confirm any significant superiority of 5% topical RJ over placebo for the treatment of DFUs.     

Autologous wound margin point columnar full-thickness skin grafting combined with negative pressure wound therapy improves wound healing in refractory diabetic foot ulcers

Diabetic lower extremity ulcers (DLEUs) are a severe complication of diabetes mellitus (DM) and are difficult to heal. This study aimed to explore the efficacy of autologous point columnar full-thickness skin graft taken from the ulcer wound margin combined with negative pressure wound therapy (NPWT) in refractory DLEUs. This is a prospective cohort study. A total of 40 inpatients with refractory DLEUs were recruited in the Diabetes Foot Center of Guangxi Zhuang Autonomous Region People's Hospital from October 2019 to November 2021. According to the doctors' professional suggestions and the patients' personal wishes, these enrolled patients were divided into two groups based on different topical wound management: the graft group (n = 18) and the conventional wound therapeutic (CWT) group (n = 22). The efficacy evaluations included the time to complete re-epithelialization of the wound and healing speed within 14 days of graft treatment or after 14 days of graft treatment in the two groups. Before the treatment, the graft group had a significantly larger ulcer area than the CWT group [27.22 (15.28, 46.59) versus 10.92 (7.00, 24.93) cm², P < .01]. However, the time to complete wound re-epithelialization in the graft group was shorter than in the CWT group [58.22 ± 30.60 versus 86.09 ± 49.54 d, P < .05]. Meanwhile, the healing speed in graft group was markedly faster than in CWT group, whether within 14 days [0.60 (0.40, 0.92) versus 0.16 (0.07, 0.34) cm²/d, P < .01] or after 14 days of graft treatment [0.57 (0.45, 0.91) versus 0.13 (0.08, 0.27) cm²/d, P < .01]. However, the total treatment cost in the graft group was lower than in the CWT group [419.59 ± 137.20 versus 663.97 ± 497.02 $, P < .05]. The novel treatment modality of autologous full-thickness skin graft taken from the ulcer wound margin combined with NPWT has hereby proposed for the first time, and is a safe, effective, and reliable method with a good performance-to-cost ratio to promote wound healing and shorten the healing time for DLEUs.