Intralesional injections of Citoprot-P (recombinant human epidermal growth factor) in advanced diabetic foot ulcers with risk of amputation

To investigate the efficacy and safety of recombinant human epidermal growth factor (rhEGF) in advanced diabetic foot ulcers (DFU) A double-blind trial was carried out to test two rhEGF dose levels in type 1 or 2 diabetes patients with Wagner's grade 3 or 4 ulcers, with high risk of amputation. Subjects were randomised to receive 75 (group I) or 25 mug (group II) rhEGF through intralesional injections, three times per week for 5-8 weeks together with standardised good wound care. Endpoints were granulation tissue formation, complete healing and need of amputation. Safety was assessed by clinical adverse events (AEs) and laboratory evaluations. Forty-one patients were included. After 5-8 weeks of treatment, 83% patients in the higher dose group and 61% in group II achieved useful granulation tissue covering more than 98% of the wound area. At long-term assessment, 13 (56.5%) patients healed in group I and 9 (50%) in group II. The mean time to complete healing in group I was 20.6 weeks (95% CI: 17.0-24.2) and 19.5 weeks (16.3-22.7) in group II. After 1-year follow-up, only one patient relapsed. Amputation was not necessary in 65% and 66.7% of groups I and II, respectively. The AEs rates were similar. The most frequent were sepsis (33%), burning sensation (29%), tremors, chills and local pain (25% each). rhEGF local injection enhances advanced DFU healing and reduces the risk of major amputation. No dose dependency was observed.     

Epidermal growth factor‐containing wound closure enhances wound healing in non‐diabetic and diabetic rats

Background: This study was designed to elucidate the in vivo efficacy of epidermal growth factor (EGF) on wound healing in non diabetic and diabetic rats. Methods: Ninety‐six male Wistar‐Albino rats were randomly divided into six groups. Saline‐moistened gauze, pure gelatin or EGF in gelatin‐microsphere dressings were used in a dermal excision model in both normal and streptomycin‐induced diabetic rats. Wound healing was evaluated on day 7 and 14. Reduction in wound area, hydroxypyroline content and tensile strength of the wound were evaluated in each rat. Tissue samples taken from the wounds were examined histopathologically for reepithelialisation, cellular infiltration, number of fibroblasts, granulation and neovascularisation. Results: On day 7, the use of EGF‐containing dressing was observed to reduce the wound area better when compared with the other dressings tested. This effect was significant in normal rats rather than diabetic rats. The difference in reduction of wound area did not persist on day 14. No significant effect on hydroxyproline content of the wound was found with EGF‐containing dressing in either normal or diabetic rats. There was a statistically significant increase in tensile strength values of EGF‐applied non diabetic rats over the 14 day period. An increase in tensile strength was prominent in also EGF‐applied diabetic rats on day 14. Histological examination revealed higher histopathologic scores in EGF‐applied diabetic and non diabetic rats. Conclusion: These findings implicate that use of EGF in gelatin‐microsphere dressings improves wound healing both in normal and diabetic rats.     

Relationship between maceration and wound healing on diabetic foot ulcers in Indonesia: a prospective study

The aim of this study was to clarify the relationship between maceration and wound healing. A prospective longitudinal design was used in this study. The wound condition determined the type of dressings used and the dressing change frequency. A total of 62 participants with diabetic foot ulcers (70 wounds) were divided into two groups: non‐macerated (n = 52) and macerated wounds (n = 18). Each group was evaluated weekly using the Bates–Jensen Wound Assessment Tool, with follow‐ups until week 4. The Mann–Whitney U test showed that the changes in the wound area in week 1 were faster in the non‐macerated group than the macerated group (P = 0·02). The Pearson correlation analysis showed a moderate correlation between maceration and wound healing from enrolment until week 4 (P = 0·002). After week 4, the Kaplan–Meier analysis showed that the non‐macerated wounds healed significantly faster than the macerated wounds (log‐rank test = 19·378, P = 0·000). The Cox regression analysis confirmed that maceration was a significant and independent predictor of wound healing in this study (adjusted hazard ratio, 0·324; 95% CI, 0·131–0·799; P = 0·014). The results of this study demonstrated that there is a relationship between maceration and wound healing. Changes in the wound area can help predict the healing of wounds with maceration in clinical settings.     

Intralesional allogeneic adipose-derived stem cells application in chronic diabetic foot ulcer: Phase I/2 safety study

BackgroundImpaired wound healing is a major cause of morbidity in diabetic patients by causing chronic ulcers. This study aimed to investigate the safety and outcomes after intralesional allogeneic adipose-derived mesenchymal stem cells injection in chronic diabetic foot ulcers.MethodsTwenty patients (12 male and eight female) were involved in the study. We randomized the patients into two groups of 10 patients each. The study group was treated with allogeneic adipose-derived mesenchymal stem cells injection with standard diabetic wound care. The control group received only standard diabetic wound care. Patient demographics, wound characteristics, wound closure time, amputation rates and clinical scores were evaluated.ResultsThe mean age was 57.3 ± 6.6 years. The mean follow-up duration was 48.0 (range, 26–50) months. Wound closure was achieved in 17 of 20 lesions (study group, 9 lesions; control group, 8 lesions; respectively). The mean time to wound closure was 31.0 ± 10.7 (range, 22–55) days in the study group, 54.8 + 15.0 (range, 30–78) days in the control group (p = 0.002). In three patients, minor amputations were performed (one patient in study group; two patients in the control group, p = 0.531). There was a significant difference between groups in terms of postoperative Short Form 36- physical functioning (p = 0.017) and Short Form 36-general health (p = 0.010).ConclusionAllogeneic adipose-derived mesenchymal stem cells injection was found to be a safe and effective method with a positive contribution to wound-healing time in the treatment of chronic diabetic foot ulcers.     

The combined effect of recombinant human epidermal growth factor and erythropoietin on full‐thickness wound healing in diabetic rat model

Diabetic wound is a chronic wound in which normal process of wound healing is interrupted. Lack of blood supply, infection and lack of functional growth factors are assumed as some of the conditions that lead to non‐healing environment. Epidermal growth factor (EGF) acts primarily to stimulate epithelial cell growth across wound. Erythropoietin (EPO) is a haematopoietic factor, which stimulates the production, differentiation and maturation of erythroid precursor cells. This study hypothesised combining these two factors, non‐healing process of diabetic wound will be compensated and eventually lead to acceleration of wound healing compared with single growth factor treatment. A total of 30 diabetic Sprague–Dawley rats were divided into three treatment groups (single treatment of rh‐EPO or rh‐EGF or combined treatment on a full‐thickness skin wound). To assess the wound healing effects of the components, the wound size and the healing time were measured in each treatment groups. The skin histology was examined by light microscopy and immunohistochemical analysis of proliferating markers was performed. The combined treatment with rh‐EPO and rh‐EGF improved full‐thickness wound significantly (P < 0·05) accelerating 50% healing time with higher expression of Ki‐67 compared with single growth factor‐treated groups. The combined treatment failed to accelerate the total healing time when compared with single growth factor treatments. However, the significant improvement were found in wound size reduction in the combined treatment group on day 4 against single growth factor‐treated groups (P < 0·05). This study demonstrated that the combined treatment of rh‐EPO and rh‐EGF improved the wound healing possibly through a synergistic action of each growth factor. This application provides further insight into combined growth factor therapy on non‐healing diabetic wounds.     

An investigation on burn wound healing in rats with chitosan gel formulation containing epidermal growth factor

Various studies have shown that chitosan is effective in promoting wound healing. In this study, we aimed to develop an effective chitosan gel formulation containing epidermal growth factor (EGF), and to determine the effect on healing of second-degree burn wounds in rats. Ten micrograms per millilitre EGF in 2% chitosan gel was prepared. In an in vitro study to investigate release of EGF from the formulations, the release rate was 97.3% after 24 h. In in vivo studies, animals were divided into six groups as follows: silver sulfadiazine [Silverdin cream (SIL)], chitosan gel with and without EGF (EJ, J), EGF solution (ES) and untreated control groups [unburned (S) and untreated (Y) rats] applied groups, respectively. A uniform deep second-degree burn of the backskin was performed with water heated to 94+/-1 degrees C during a 15-s exposure. The EGF formulations were repeatedly applied on the burned areas with a dose of 0.160 microg/cm2 for 14 days (one application per day). Healing of the wounds was evaluated immunohistochemically, histochemically and histologically on the tissue samples. When the results were evaluated immunohistochemically, there were significant increases in cell proliferation observed in the EGF containing gel applied group (p<0.001). The histochemical results showed that the epithelization rate in the EJ group was the highest compared to the ES group results (p<0.001). The histological results indicated and supported these findings. It can be concluded that a better and faster epithelization was observed in the EJ group compared to the other groups.     

Safety,efficacy and pitfalls of fibrocyte application in the treatment of diabetic foot ulcer

Fibrocytes are unique bone marrow‐derived cells with great potential in wound healing. Hence, the aim of this study was to determine the safety and efficacy of the applied circulating fibrocytes in the treatment of non healing diabetic foot ulcers. Peripheral blood mononuclear cells were isolated by centrifugation through Ficoll–Paque method. After 3 days, the non adherent cells were removed by a single, gentle aspiration. Adherent cells were cultured in the same medium for 10 days. The cells were characterised using mouse anti‐human‐CD45‐fluorescein isothiocyanate (FITC) and mouse anti‐human–collagen I, and also characterised by immunofluorescence microscopy using the above mentioned antibodies. Sterility measures were applied for clinical evaluation. Based on the literature review, cell transplantation generally requires at least 3 × 10⁶ cells regarding efficacy measures. As fibrocytes are non proliferating cells, 350 ml patient's blood is required to prepare patient‐specific serum before cell isolation and culture, and 85 ml patient's blood is needed for cell isolation and differentiation on cell transplantation applications. In our survey, no diabetic patient was inclined to be donor of such blood volume, mainly because of their pre‐assumption that they are anaemic. It is concluded that fibrocytes do not seem to be candidate cells for cell therapy in the treatment of diabetic foot ulcers because of the rarity of this cell population in circulation.     

负压封闭引流促进糖尿病足溃疡的愈合

目的分析负压封闭引流(vacuum sealing drainage,VSD)能否促进糖尿病足溃疡的愈合。方法回顾分析自2015年1月至2019年12月,北部战区总医院烧伤整形科收治的糖尿病足溃疡患者60例,并根据患者的治疗方式分为常规治疗组(30例)和VSD治疗组(30例)。统计对比分析两组患者的平均换药次数、平均愈合时间、疼痛程度及满意度。搜集治疗前和治疗14 d后的肉芽组织进行HE染色和VEGF免疫组化染色,分析创面愈合情况以及VEGF的表达情况。结果VSD治疗组换药次数[(5.40±0.28)次]显著少于常规治疗组[(31.41±1.11)次],组间比较P<0.05;VSD治疗组平均愈合时间(29.38±0.63)d显著短于常规治疗组(50.81±2.15)d,组间比较P<0.05;VSD治疗组患者的痛苦程度明显轻于常规治疗组,满意度显著优于常规治疗组,组间比较P<0.05。结论VSD治疗能够促进创面成纤维细胞的增殖、减少炎性细胞的浸润、促进VEGF的表达及创面的愈合。     

Current scenario of traditional medicines in management of diabetic foot ulcers: A review

Diabetic foot infections and diabetic foot ulcers (DFU) cause significant suffering and are often recurring. DFU have three important pathogenic factors, namely, microangiopathy causing local tissue anoxia, neuropathy making the foot prone to injuries from trivial trauma, and local tissue hyperglycaemia favouring infection and delaying the wound healing. DFU have been the leading cause for non-traumatic amputations of part or whole of the limb. Western medicines focus mainly on euglycaemia, antimicrobials, debridement and wound cover with grafts, and off-loading techniques. Advances in euglycaemic control, foot care and footwear, systemic antimicrobial therapy, and overall health care access and delivery, have resulted in an overall decrease in amputations. However, the process of wound care after adequate debridement remains a major cost burden globally, especially in developing nations. This process revolves around two basic concerns regarding control/eradication of local infection and promotion of faster healing in a chronic DFU without recurrence. Wound modulation with various dressings and techniques are often a costly affair. Some aspects of the topical therapy with modern/Western medicines are frequently not addressed. Cost of and compliance to these therapies are important as both the wounds and their treatment are “chronic.” Naturally occurring agents/medications from traditional medicine systems have been used frequently in different cultures and nations, though without adequate clinical base/relevance. Traditional Chinese medicine involves restoring yin-yang balance, regulating the ‘chi’, and promoting local blood circulation. Traditional medicines from India have been emphasizing on ‘naturally’ available products to control wound infection and promote all the aspects of wound healing. There is one more group of chemicals which are not pharmaceutical agents but can create acidic milieu in the wound to satisfy the above-mentioned basic concerns. Various natural and plant derived products (e.g., honey, aloe vera, oils, and calendula) and maggots are also used for wound healing purposes. We believe that patients with a chronic wound are so tired physically, emotionally, and financially that they usually accept native traditional medicine which has the same cultural base, belief, and faith. Many of these products have never been tested in accordance to “evidence-based medicine.” There are usually case reports and experience-based reports about these products. Recently, there have been some trials (in vitro and in vivo) to verify the claims of usage of traditional medicines in management of DFU. Such studies show that these natural products enhance the healing process by controlling infection, stimulating granulation tissue, antimicrobial action, promoting fibroblastic activity and collagen deposition, etc. In this review, we attempt to study and analyse the available literature on results of topical traditional medicines, which are usually advocated in the management of DFU. An integrated and ‘holistic’ approach of both modern and traditional medicine may be more acceptable to the patient, cost effective, and easy to administer and monitor. This may also nevertheless lead to further improvement in quality of life and decrease in the rates of amputations for DFU.     

Healing enhancement of diabetic wounds by locally infiltrated epidermal growth factor is associated with systemic oxidative stress reduction

The diabetic foot ulcer (DFU) is the leading cause of lower extremity amputation worldwide and is directly associated with comorbidity, disability and mortality. Oxidative stress mechanisms have been implicated in the pathogenesis of these wounds. Intra‐lesional infiltration of epidermal growth factor has emerged as a potential therapeutic alternative to allow for physiological benefit while avoiding the proteolytic environment at the centre of the wound. The aim of this study was to characterise the response of patients with DFUs to epidermal growth factor treatment in terms of redox status markers. Experimental groups included patients with DFUs before and 3–4 weeks after starting treatment with epidermal growth factor; compensated and non‐compensated diabetic patients without ulcers; and age‐matched non‐diabetic subjects. Evaluations comprised serum levels of oxidative stress and antioxidant reserve markers. Patients with DFUs exhibited the most disheveled biochemical profile, with elevated oxidative stress and low antioxidant reserves, with respect to non‐ulcerated diabetic patients and to non‐diabetic subjects. Epidermal growth factor intra‐lesional administration was associated with a significant recovery of oxidative stress and antioxidant reserve markers. Altogether, our results indicate that epidermal growth factor intra‐ulcer therapy contributes to restore systemic redox balance in patients with DFUs.     

Management of negative pressure wound therapy in the treatment of diabetic foot ulcers

Diabetic foot (DF) is a common complication of diabetes and the first cause of hospital admission in diabetic patients. In recent years several guidelines have been proposed to reinforce the the management of DF with a notable increase in diabetes knowledge and an overall reduction of amputations. Significant improvements have been reached in the treatment of diabetic foot ulcers (DFUs) and nowadays clinicians have several advanced medications to apply for the best local therapy. Among these, negative pressure wound therapy (NPWT) is a useful adjunct in the management of chronic and complex wounds to promote healing and wound bed preparation for surgical procedures such as skin grafts and flap surgery. NPWT has shown remarkable results although its mechanisms of action are not completely understood. In this paper, we offer a complete overview of this medication and its implication in the clinical setting. We have examined literature related to NPWT concerning human, animal and in vitro studies, and we have summarized why, when and how we can use NPWT to treat DFUs. Further we have associated our clinical experience to scientific evidence in the field of diabetic foot to identify a defined strategy that could guide clinician in the use of NPWT approaching to DFUs.     

糖尿病足溃疡患者创面局部注射胰岛素对全身血糖及创面的影响

目的 观察糖尿病足溃疡患者创面局部注射胰岛素对全身血糖和创面肉芽组织形成的影响. 方法 选择2009年6月-2010年6月在笔者单位住院治疗的糖尿病足患者32例,按随机数字表法分为胰岛素组和对照组,每组16例.所有患者预先清创.(1)胰岛素组:将胰岛素计算剂量的1/2用生理盐水稀释成1 mL后,浸润注射于溃疡创面基底部,另1/2计算量按常规行腹部皮下注射,均为2次/d.(2)对照组:将胰岛素计算剂量的全量常规注射于腹部皮下,溃疡创面基底部浸润注射1 mL生理盐水,均为2次/d.2组患者均连续注射7d.于患者每次注射前及注射后0.5、1.0、2.0、4.0 h,分别检测其空腹血糖值.于首次注射前及注射3、5、7 d,评估创面肉芽组织生长程度;取创面组织标本观察CD34表达情况,据此计算创面微血管密度(MVD).对实验数据行t检验.结果 2组患者观察期内空腹血糖值维持在6.6～12.8(10.0±2.2)mmol/L,各时相点组间比较,差异均无统计学意义(t值为0.000～2.209,P值均大于0.05).注射第5天起,胰岛素组患者局部创面肉芽组织明显增多;第7天达生长高峰[(59.06±1.58％],与对照组[(23.61±1.57)％]比较,差异有统计学意义(t=17.420,P=0.0.000).CD34表达情况显示,胰岛素组注射3 d起有新生血管形成,但此时MVD与对照组接近(t=0.0247,P＞0.05);注射5、7d,胰岛素组创面组织MVD每200倍视野中分别为(8.34±0.48)、(11.22±0.97)个,明显多于对照组的(4.42±0.14)、(5.44±1.13)个,t值分别为16.568、27.664,P值均小于0.01. 结论 糖尿病足溃疡患者创面局部注射胰岛素对全身血糖有较明显影响,能加速肉芽组织生长,促进创面愈合.     

Effect of substance P released from peripheral nerve ending on endogenous expression of epidermal growth factor and its receptor in wound healing

Objective: To explore the relationship between substance P (SP) released from peripheral nerve endings and the expression of epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) during wound bealing. Methods: Fifty Wistar rats were randomly divided into 2 groups, injury group and capsaicin group. In the injury group, a full-thickness skin wound on the back of the rat was taken. The wound edge and granulation tissues were taken on the 1st, 3rd, 6th, 9th, 12th days after injury, respectively. In the capsaicin group, capsaicin was injected subcutaneously on the back of the rats to destroy the sensory nerve to prevent the secretion of SP, then a wound and sample was made in the same way.Immunohistochemistry and in situ hybridization were employed to detect the expression of SP, EGF/EGFR, and EGF mRNA/EGFR mRNA in the granulation tissues.Results: In the injury group,immunohistochemical stain of SP and EGF/EGFR was located on the hair follicles and sebaceous glands at the 1st day. And the stain of SP was obvious at the 3rd day in the granulation tissues, then decreased gradually. EGF/EGFR was at low level at the 3rd day, then increased gradually and reached the peak at the 9th day, then declined. In the capsaicin group, the stain of SP and EGF/EGFR was faint and without obvious change during the wound healing process. The tendency of the EGF mRNA/EGFR mRNA expression was similar to that of EGF/EGFR. Conclusions: During wound healing, SP may promote the healing process by affecting the expression of EGF/EGFR in the erunuation tissues.     

表皮生长因子不同用药方法对供皮区治疗的作用

目的　探索外用重组人表皮生长因子治疗供皮区创面的最佳用药方法 ,以指导临床应用。方法　设生理盐水治疗为自身对照 ,选择三种用rhEGF的方法 (每日 1次法 ,每日 3次法 ,每日 1次加保湿法 ) ,进行供皮区创面愈合的比较性研究。结果　和对照组相比 ,rhEGF可有效促进供皮区创面愈合 (P <0 .0 1 )。三种用药方法之间比较 ,差别具有显著性意义 (P <0 .0 5) ,每日 1次加保湿法和每日 3次法均能进一步缩短创面愈合时间。结论　从方便、经济与合理的角度考虑 ,每日 1次加保湿法为临床首选     

Effect of noncontact normothermic wound therapy on the healing of neuropathic (diabetic) foot ulcers: An interim analysis of 20 patients

This is the interim analysis of a prospective, randomized, controlled study comparing diabetic foot ulcer healing in patients being treated with either noncontact normothermic wound therapy (Warm-UP; Augustine Medical Inc. Eden Prairie, MN) applied for 1 hour 3 times daily until healing or 12 weeks, or standard care (saline-moistened gauze applied once a day). Surgical debridement and adequate foot off-loading was provided to both groups. Evaluations were performed weekly and consisted of acetate tracings, wound assessment, and serial photography. Twenty patients have completed the trial and both treatment groups were distributed evenly (N = 10). Ulcers treated with noncontact normothermic wound therapy had a greater mean percent wound closure than control-treated ulcers at each evaluation point (weeks 1-12). After 12 weeks, 70% of the wounds treated with noncontact normothermic wound therapy were healed compared with 40% for the control group. In this subset of patients there have been no adverse events associated with noncontact normothermic wound therapy.     

Use of a Nanoflex powder dressing for wound management following debridement for necrotising fasciitis in the diabetic foot

This paper discusses the application of Nanoflex powder dressing for management of complex soft tissue wounds. A case report is presented detailing the management of a 43‐year‐old Native American woman with diabetes mellitus who required serial debridements for necrotising fasciitis. Following debridement, the patient was left with a large dorsal foot wound and was transitioned through multiple advanced wound healing modalities. Negative pressure wound therapy (NPWT) was initially utilised in the early postoperative setting to control drainage and to promote granulation tissue; the patient was subsequently transitioned to a Nanoflex powder dressing on postoperative day 4. She reported a decrease in pain associated with dressing changes when transitioned from NPWT to the use of Nanoflex powder dressing. We hypothesise that this pain reduction is the result of a light cooling effect of the exudate‐controlling dressing and subsequent reduction in inflammation as well as the total contact nature of the dressing. Nanoflex powder dressings are a recently developed advanced wound healing modality with promise in the management of complex soft tissue wounds, both as a primary wound dressing as well as a delivery platform for analgesics, antimicrobials and pro‐angiogenic compounds.     

Non-coding RNAs: Role in diabetic foot and wound healing

Diabetic foot ulcer (DFU) and poor wound healing are chronic complications in patients with diabetes. The increasing incidence of DFU has resulted in huge pressure worldwide. Diagnosing and treating this condition are therefore of great importance to control morbidity and improve prognosis. Finding new markers with potential diagnostic and therapeutic utility in DFU has gathered increasing interest. Wound healing is a process divided into three stages: Inflammation, proliferation, and regeneration. Non-coding RNAs (ncRNAs), which are small protected molecules transcribed from the genome without protein translation function, have emerged as important regulators of diabetes complications. The deregulation of ncRNAs may be linked to accelerated DFU development and delayed wound healing. Moreover, ncRNAs can be used for therapeutic purposes in diabetic wound healing. Herein, we summarize the role of microRNAs, long ncRNAs, and circular RNAs in diverse stages of DFU wound healing and their potential use as novel therapeutic targets.     

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.     

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.     

A parallel open-label trial to evaluate microbial cellulose wound dressing in the treatment of diabetic foot ulcers

The purpose of this study was to compare the rate of wound healing in diabetic foot ulcers (DFU) using either a microbial cellulose (MC) wound dressing or Xeroform? Petrolatum gauze. In a parallel, open‐label trial in which the primary outcome was the rate of wound healing and the time to wound closure, 15 ulcers in type II diabetic patients received an MC dressing. Wounds in 19 control patients with type II diabetes were treated with a Xeroform gauze dressing. All wounds were non infected, Wagner stage II or III and received standard care including debridement, non weight bearing limb support and weekly wound evaluation. The mean time to heal in the MC (±SE) treated group was 32 days ± 2·5 and for controls it was 48 days ± 4·7 (P < 0·01). The rate of weekly wound closure (mean ± SE) was 1·7 times faster in the MC‐treated group (cellulose treated, ?5·04% per week ± 0·38 versus control, ?2·93% per week ± 0·19), (P < 0·001). Among covariants tested by univariate regression, only the original wound area correlated with the time to wound closure (P < 0·001). In conclusion, with the provision of current standards of care, the application of an MC dressing to a diabetic ulcer may enhance the rate of wound healing and shorten the time course of epithelisation.