Platelet-rich plasma versus platelet-poor plasma in the management of chronic diabetic foot ulcers: a comparative study

Non healing diabetic foot ulcers and the resulting potential amputations present significant costs to the health care system and reduce patient quality of life. The goal of diabetic foot ulcer treatment is to obtain wound closure as expeditiously as possible. The use of platelet-rich plasma (PRP) to enhance wound healing has increased dramatically over the last decade. However, controversies exist in the literature regarding the added benefit of this procedure. The aim of this study is to investigate the efficiency of platelet releasate on the healing of chronic diabetic ulcers in comparison with platelet-poor plasma (PPP). This study included 24 patients with chronic diabetic ulcers. They were systematically randomised into two groups: PRP group (n = 12) and PPP group (n = 12). The results showed that healing in PRP group was significantly faster (P < 0·005). PRP enhances healing of chronic diabetic foot ulcers.     

Two-step autologous grafting using HYAFF scaffolds in treating difficult diabetic foot ulcers: results of a multicenter, randomized controlled clinical trial with long-term follow-up

This study evaluated the efficacy and tolerability of an autologous tissue-engineered graft--a 2-step HYAFF autograft--in the treatment of diabetic foot ulcers compared with standard care. In all, 180 patients with dorsal or plantar diabetic foot ulcers (unhealed for ≥1 month) were randomized to receive Hyalograft-3D autograft first and then Laserskin autograft after 2 weeks (n = 90; treatment group) or nonadherent paraffin gauze (n = 90; control group). Efficacy and adverse events were assessed weekly for 12 weeks, at 20 weeks, and at 18 months. The primary efficacy outcome was complete ulcer healing at 12 weeks. Wound debridement, adequate pressure relief, and infection control were provided to both groups. At 12 weeks, complete ulcer healing was similar in both groups (24% of treated vs 21% controls). A 50% reduction in ulcer area was achieved significantly faster in the treatment group (mean 40 vs 50 days; P = .018). Weekly percentage ulcer reduction was consistently higher in the treatment group. At 20 weeks, ulcer healing was achieved in 50% of the treated group as compared with 43% of controls. Dorsal ulcers had a 2.17-fold better chance of wound healing per unit time following autograft treatment (P = .047). In a subgroup with hard-to-heal ulcers, there was a 3.65-fold better chance of wound healing following autograft treatment of dorsal ulcers (P = .035). Adverse events were similar in both groups. The study results demonstrated the potential of this bioengineered substitutes to manage hard-to-heal dorsal foot ulcers.     

Becaplermin gel in the treatment of pressure ulcers: a phase II randomized, double-blind, placebo-controlled study

Pressure ulcers are associated with significant rates of morbidity and mortality, particularly in the geriatric and spinal cord-injured populations. Newer pharmacologically active therapies include the use of topically applied recombinant human platelet-derived growth factor-BB (becaplermin), the active ingredient in REGRANEX) (becaplermin) Gel 0.01%, which has been approved in the United States for treatment of lower extremity diabetic neuropathic ulcers that extend into the subcutaneous tissue or beyond and have an adequate blood supply. In this study, the efficacy of becaplermin gel in the treatment of chronic full thickness pressure ulcers was compared with that of placebo gel. A total of 124 adults (>/= 18 years of age) with pressure ulcers were assigned randomly to receive topical treatment with becaplermin gel 100 microg/g (n = 31) or 300 microg/g (n = 32) once daily alternated with placebo gel every 12 hours, becaplermin gel 100 microg/g twice daily (n = 30), or placebo (sodium carboxymethylcellulose) gel (n = 31) twice daily until complete healing was achieved or for 16 weeks. All treatment groups received a standardized regimen of good wound care throughout the study period. Study endpoints were the incidence of complete healing, the incidence of >/= 90% healing, and the relative ulcer volume at endpoint (endpoint/baseline). Once-daily treatment of chronic pressure ulcers with becaplermin gel 100 microg/g or 300 microg/g significantly increased the incidences of complete and >/= 90% healing and significantly reduced the median relative ulcer volume at endpoint compared with that of placebo gel (p < 0.025 for all comparisons). Becaplermin gel 300 microg/g did not result in a significantly greater incidence of healing than that observed with 100 microg/g. Treatment with becaplermin gel was generally well tolerated and the incidence of adverse events was similar among treatment groups. In conclusion, once-daily application of becaplermin gel is efficacious in the treatment of chronic full thickness pressure ulcers.     

Evaluation of the use of prognostic information for the care of individuals with venous leg ulcers or diabetic neuropathic foot ulcers

This is a randomized factorial design clinical trial that investigates the efficacy and feasibility of providing prognostic information on wound healing. Prognostic information was provided based on baseline or 4-week wound characteristics. Healing rates were then determined at 24 weeks for venous leg ulcers and 20 weeks for diabetic neuropathic foot ulcers. Centers that had access to baseline information for venous leg ulcer prognosis had an odds ratio (OR) of healing of 1.42 (95% confidence interval [CI]: 1.03, 1.95) while centers that had access to information at 4 weeks had an OR of healing of 1.43 (95% CI: 1.05, 1.95) compared with controls. Diabetic neuropathic foot ulcer patients treated in centers that had been randomized to receive only 4-week prognostic information were more likely to heal than individuals seen in centers randomized to receive no intervention (OR 1.50, 95% CI: 1.05, 2.14). Our study found that it is feasible and efficacious to provide prognostic information on venous leg ulcers and diabetic neuropathic foot ulcers in a wound care setting using an existing administrative database. This intervention was easy to administer and likely had low associated costs. This method of dispersing prognostic information to healthcare providers should be expanded to include recently published treatment algorithms.     

A randomized,controlled trial of Promogran (a collagen/oxidized regenerated cellulose dressing) vs standard treatment in the management of diabetic foot ulcers

HYPOTHESIS: Promogran, a wound dressing consisting of collagen and oxidized regenerated cellulose, is more effective that standard care in treating chronic diabetic plantar ulcers. DESIGN: Randomized, prospective, controlled multicenter trial. SETTING: University teaching hospitals and primary care centers. PATIENTS: A total of 276 patients from 11 centers were enrolled in the study. The mean age of the patients was 58.3 years (range, 23-85 years). All patients had at least 1 diabetic foot ulcer. INTERVENTIONS: Patients were randomized to receive Promogran (n = 138) or moistened gauze (control group; n = 138) and a secondary dressing. Dressings were changed when clinically required. The maximum follow-up for each patient was 12 weeks. MAIN OUTCOME MEASURE: Complete healing of the study ulcer (wound). RESULTS: After 12 weeks of treatment, 51 (37.0%) Promogran-treated patients had complete wound closure compared with 39 (28.3%) control patientss, but this difference was not statistically significant (P =.12). The difference in healing between treatment groups achieved borderline significance in the subgroup of patients with wounds of less than 6 months' duration. In patients with ulcers of less than 6 months' duration, 43 (45%) of 95 Promogran-treated patients healed compared with 29 (33%) of 89 controls (P =.056). In the group with wounds of at least 6 months' duration, similar numbers of patients healed in the control (10/49 [20%]) and the Promogran (8/43 [19%]; P =.83) groups. No differences were seen in the safety measurements between groups. Patients and investigators expressed a strong preference for Promogran compared with moistened gauze. CONCLUSIONS: Promogran was comparable to moistened gauze in promoting wound healing in diabetic foot ulcers. It showed an additional efficacy for ulcers of less than 6 months' duration that was of marginal statistical significance. Furthermore, Promogran had a safety profile that was similar to that of moistened gauze, with greater user satisfaction. Therefore, Promogran may be a useful adjunct in the management of diabetic foot ulceration, especially in ulcers of less than 6 months' duration.     

Evidence‐based chronic ulcer care and lower limb outcomes among Pacific Northwest veterans

Evidence‐based ulcer care guidelines detail optimal components of care for treatment of ulcers of different etiologies. We investigated the impact of providing specific evidence‐based ulcer treatment components on healing outcomes for lower limb ulcers (LLU) among veterans in the Pacific Northwest. Components of evidence‐based ulcer care for venous, arterial, diabetic foot ulcers/neuropathic ulcers were abstracted from medical records. The outcome was ulcer healing. Our analysis assessed the relationship between evidence‐based ulcer care by etiology, components of care provided, and healing, while accounting for veteran characteristics. A minority of veterans in all three ulcer‐etiology groups received the recommended components of evidence‐based care in at least 80% of visits. The likelihood of healing improved when assessment for edema and infection were performed on at least 80% of visits (hazard ratio [HR] = 3.20, p = 0.009 and HR = 3.54, p = 0.006, respectively) in patients with venous ulcers. There was no significant association between frequency of care components provided and healing among patients with arterial ulcers. Among patients with diabetic/neuropathic ulcers, the chance of healing increased 2.5‐fold when debridement was performed at 80% of visits (p = 0.03), and doubled when ischemia was assessed at the first visit (p = 0.045). Veterans in the Pacific Northwest did not uniformly receive evidence‐based ulcer care. Not all evidence‐based ulcer care components were significantly associated with healing. At a minimum, clinicians need to address components of ulcer care associated with improved ulcer healing.     

Neurogenic factors in the impaired healing of diabetic foot ulcers

BACKGROUND: We hypothesize that the reduced innervation of skin can be observed both in clinically neuropathic and non-neuropathic diabetic foot ulcers and can contribute to low inflammatory cell infiltration. MATERIALS AND METHODS: Twenty patients with type 2 diabetes and active foot ulcers, without clinical evidence of peripheral sensory neuropathy (n = 12) and with sensory neuropathy (n = 8) were involved in this study. Biopsies from ulcer margin were examined immunohistochemically. RESULTS: Studies revealed presence of protein gene product 9.5 (PGP9.5)+ nerve endings only in reticular dermis in 3 of 12 non-neuropathic subjects, however, regenerating GAP-43+ endings were seen in dermis of almost all specimens. Lack of substance P+ nerve endings was characteristic for both groups. The reduced distribution of calcitonin gene-related peptide+ nerves in epidermis and dermis was seen mainly in neuropathic group. In neo-epidermis lack of nerve growth factor expression was observed in both groups, whereas neurotrophin 3 immunostaining was characteristic for neuropathic specimens (P < 0.03). Expression of trkA and trkC receptors did not differ significantly between groups. Low inflammatory cell infiltration and moderate presence of fibroblasts was characteristic for all studied specimens. CONCLUSIONS: The observed reduction of foot skin innervation and neurogenic factors expression can be correlated with low inflammatory cell accumulation and subsequently leads to the observed chronicity of diabetic foot ulcer healing process in both neuropathic and non-neuropathic patients.     

Determinants of Success After Metatarsal Head Resection for the Treatment of Neuropathic Diabetic Foot Ulcers

Metatarsal head resection (MHR) is an effective option for the treatment of nonhealing neuropathic diabetic foot ulcers. The present study aimed to identify factors that predict treatment success for neuropathic diabetic foot ulcers undergoing metatarsal head resection. In this prospective interventional case series, 30 consecutive diabetic patients with documented nonischemic neuropathic plantar diabetic foot ulcers beneath the metatarsal head who underwent MHR were included. The study endpoint was demographic indicators of early and late postoperative outcomes. Patients were followed up for 1 to 66 months (mean 37.6 months). Except for 1 patient, all subjects’ wounds (96.6%) healed after metatarsal head resection within an average of 35 days. One of the operated patients (3.4%) suffered short-term complications; long-term complications occurred in 23.3% of the patients. One patient (3.4%) experienced ulcer recurrence, 3 patients (10%) developed wound infection, and transfer lesions occurred in 3 other patients (10%) during the follow-up period. Using 3 estimators including ordinary least squares (OLS), White's heteroscedastic standard errors, and bootstrapping procedure, we could not find any statistically significant demographic feature related to ulcer healing. Using regression modeling, we could not find any evidence for a role of age, sex, weight, height, BMI, duration of ulcer until MHR, and duration of diabetes mellitus (years since diabetes diagnosis) affecting the outcome of MHR. Hence, demographic features, duration of ulcer until MHR, and years with diabetes did not affect the outcome of MHR. In conclusion, the authors believe that MHR will have a high rate of success for neuropathic wound healing in this specific subset of patients regardless of demographic features, as long as there is no ischemia to impair healing by secondary intention.     

The role of surgical debridement in healing of diabetic foot ulcers

An estimated 15% of patients with diabetes mellitus will develop a foot ulcer during their lifetime. Debridement is included in multiple guidelines and algorithms for the care of patients with diabetic neuropathic foot ulcers, and it has long been considered an essential step in the protocol for treating diabetic foot ulcers. In addition to altering the environment of the chronic wound, debridement is a technique aimed at removing nonviable and necrotic tissue, thought to be detrimental to healing. This is accomplished by removing abnormal wound bed and wound edge tissue, such as hyperkeratotic epidermis (callus) and necrotic dermal tissue, foreign debris, and bacteria elements known to have an inhibitory effect on wound healing. While the rationale for surgical debridement seems logical, the evidence for its role in enhancing healing is deficient. In this paper, we systematically review five published clinical trials, which met the criteria and investigated surgical debridement of diabetic foot ulcers to enhance healing. Most existing studies are not randomized clinical trials optimized to test the relationship between debridement of diabetic foot ulcers and wound healing. Therefore, a focused, well‐designed study is needed to elucidate the effect of surgical debridement on the healing status of chronic wounds.     

糖尿病足溃疡创面的综合治疗

目的：探讨如何促进糖尿病足溃疡创面愈合,降低致残率。方法：对糖尿病足溃疡患者,在积极的内科治疗稳定病情的基础上,采用以创面清创换药,改善局部血运和促进局部组织生长,或采用整形外科手术的方法治疗。结果：52例糖尿病足溃疡创面,除1例因溃疡坏疽创面较深大合并骨髓炎行截肢外,其余均顺利修复。平均随访90．4%,疗效满意率91．5%,出现溃疡复发或有新的皮肤溃疡者8．5%。结论：在全身治疗稳定病情的基础上,积极进行创面处理和整形外科手术的综合治疗是促进糖尿病足溃疡创面早期愈合,缩短病程和降低致残率切实可行的方法。重视糖尿病足患者溃疡愈合出院后的康复指导工作至关重要。     

NorLeu3‐A(1–7) stimulation of diabetic foot ulcer healing: Results of a randomized,parallel‐group,double‐blind,placebo‐controlled phase 2 clinical trial

This randomized, double‐blind, placebo‐controlled Phase 2 clinical trial explored NorLeu³‐A(1–7) (DSC127) safety and healing efficacy in diabetic foot ulcers. Patients with chronic, noninfected, neuropathic, or neuroischemic plantar Wagner Grade 1 or 2 foot ulcers (n = 172) were screened for nonhealing. Subjects were randomized to receive 4 weeks’ once‐daily topical treatment with 0.03% DSC127 (n = 26), 0.01% DSC127 (n = 27), or Placebo (n = 24), followed by 20 weeks’ standard of care. DSC127 was assessed for safety (including laboratory values and adverse events), primary efficacy (% ulcers completely epithelialized at Week 12), and durability of effect. Baseline, demography, and safety parameters were compared between intent‐to‐treat groups and were comparable. Dose‐response curves for DSC127 effect on % area reduction from baseline at Week 12 (40% placebo; 67% 0.01% DSC127; 80% 0.03% DSC127) and 24 (23% placebo; 53% 0.01% DSC127; 95% 0.03% DSC127) followed a log‐linear pattern for both intent‐to‐treat and per‐protocol populations. Covariate analysis compared reduction in ulcer area, depth, and volume from baseline; reductions in the 0.03% DSC127 group were greater at Weeks 12 and 24. Placebo‐treated ulcers healed in a median 22 weeks vs. 8.5 weeks for 0.03%DSC127 (p = 0.04). This study provides preliminary evidence that DSC127 is safe and effective in accelerating the healing of diabetic foot ulcers.     

Thrombin peptide Chrysalin® stimulates healing of diabetic foot ulcers in a placebo-controlled phase I/II study

Thrombin and thrombin peptides play a role in initiating tissue repair. The potential safety and efficacy of TP508 (Chrysalin) treatment of diabetic foot ulcers was evaluated in a 60-subject, prospective, randomized, double-blind, placebo-controlled phase I/II clinical trial. Chrysalin in saline or saline alone was applied topically, twice weekly, to diabetic ulcers with standardized care and offloading. A dose-dependent effect was seen in the per-protocol population where 1 and 10 mug Chrysalin treatment resulted in 45 and 72% more subjects with complete healing than placebo treatment. Chrysalin treatment of foot ulcers more than doubled the incidence of complete healing (p<0.05), increased mean closure rate approximately 80% (p<0.05), and decreased the median time to 100% closure by approximately 40% (p<0.05). Chrysalin treatment of heel ulcers within this population resulted in mean closure rates 165% higher than placebos (p<0.02) and complete healing in 86% (6/7) of ulcers compared with 0% (0/5) of placebo ulcers (p<0.03). Local wound reactions and adverse events (AEs) were equal between groups with no reported drug-related changes in laboratory tests or serious AEs. These results indicate the potential safety and efficacy of Chrysalin for treatment of diabetic foot ulcers.     

Role of neuropathy and plasma nitric oxide in recurrent neuropathic and neuroischemic diabetic foot ulcers

Various factors are associated with foot ulceration, including delayed reporting of ulcers, poor glycemic control, and severity of neuropathy. Several studies have looked at the role of nitric oxide in wound healing. However, no studies have examined its role in the occurrence and recurrence of diabetic foot ulceration. In a cross-sectional study we examined the role of neuropathy, retinopathy, nephropathy, and plasma nitric oxide (estimated from plasma nitrite and nitrate) levels in diabetic patients with recurrent and non-recurrent neuropathic and neuroischemic foot ulcers. Patients with recurrent foot ulcers had higher vibration perception threshold values compared to patients with non-recurrent foot ulcers (47.4 +/- 5.7 volts versus 39.5 +/- 10.3 volts respectively, P < 0.05). In addition, subjects with recurrent foot ulcers had significantly higher plasma nitric oxide compared to subjects with non-recurrent foot ulcers (46.9 +/- 6.3 microm/L versus 30.2 +/- 2.4 microm/L respectively, P < 0.01). Multivariate logistic regression analysis adjusted for age, sex, hemoglobin A1c, presence of retinopathy and nephropathy, vibration perception threshold, plasma creatinine, and total nitric oxide, indicated that only vibration perception threshold was independently associated with the presence of an ulcer [odds ratio: 1.26 (1.10-1.46); P <0.001)] and the recurrence of foot ulcers [odds ratio: 1.13 (1.01-1.27); P =0.04)]. This study has shown that although plasma nitric oxide is higher in patients with recurrent neuropathic and neuroischemic foot ulcers, severity of neuropathy was the most important factor associated with the development and recurrence of foot ulcers in diabetic patients.     

Gastrocnemius fascia release under local anaesthesia as a treatment for neuropathic foot ulcers in diabetic patients: a short series

Background: Diabetic foot ulceration is the leading cause of major amputation in the developed world. Plantar neuropathic ulcers at the forefoot can be managed conservatively with off-loading, but treatment is not invariably successful. Achilles tendon lengthening procedures aim at increasing dorsiflexion and decreasing forefoot pressure but can be associated with complications and require prolonged postoperative immobilization to prevent tendon rupture. We assessed the feasibility and clinical outcome of a comparative minimal invasive procedure: the gastrocnemius fascia release. This technique targets the same goals but is performed under local anaesthesia and allows immediate postoperative weight bearing and ambulation.

Methods: Diabetic patients with plantar neuropathic ulcers Wagner grade 2 or 3 were recruited from our diabetic foot clinic. Patients with infected wounds or untreatable peripheral arterial disease were excluded from the study. Conservative treatment with off-loading and local wound care was attempted for six weeks and surgical procedure only contemplated upon failure. Primary end-points were improved range of dorsiflexion and time to healing. Secondary end-points were local ulcer recurrences, new plantar ulcers, and minor or major amputation. Post-operative follow-up was 12 months.

Results: Seven patients were included in the study. An improvement in dorsiflexion of 10.4° (mean) was recorded post-operatively (p?Conclusions: Gastrocnemius fascia release under local anaesthesia can be performed safely in diabetic patients with plantar neuropathic ulcers under the metatarsal heads. Clinical outcome is excellent and long-term results promising.     

Effect of systemic insulin treatment on diabetic wound healing

This study investigates if different diabetic treatment regimens affect diabetic foot ulcer healing. From January 2013 to December 2014, 107 diabetic foot ulcers in 85 patients were followed until wound healing, amputation or development of a nonhealing ulcer at the last follow‐up visit. Demographic data, diabetic treatment regimens, presence of peripheral vascular disease, wound characteristics, and outcome were collected. Nonhealing wound was defined as major or minor amputation or those who did not have complete healing until the last observation. Median age was 60.0 years (range: 31.1–90.1 years) and 58 cases (68.2%) were males. Twenty‐four cases reached a complete healing (healing rate: 22.4%). The median follow‐up period in subjects with classified as having chronic wounds was 6.0 months (range: 0.7–21.8 months). Insulin treatment was a part of diabetes management in 52 (61.2%) cases. Insulin therapy significantly increased the wound healing rate (30.3% [20/66 ulcers] vs. 9.8% [4/41 ulcers]) (p = 0.013). In multivariate random‐effect logistic regression model, adjusting for age, gender, smoking status, type of diabetes, hypertension, chronic kidney disease, peripheral arterial disease, oral hypoglycemic use, wound infection, involved side, presence of Charcot's deformity, gangrene, osteomyelitis on x‐ray, and serum hemoglobin A1C levels, insulin treatment was associated with a higher chance of complete healing (beta ± SE: 15.2 ± 6.1, p = 0.013). Systemic insulin treatment can improve wound healing in diabetic ulcers after adjusting for multiple confounding covariates.     

Clinical evaluation of recombinant human platelet – derived growth factor for the treatment of lower extremity diabetic ulcers

Purpose: The purpose of this study was to investigate the efficacy and safety of recombinant human platelet – derived growth factor (rhPDGF-BB) in a double-blind, placebo-controlled, multicenter study of patients with chronic diabetic ulcers.Methods: Patients with chronic, full-thickness, lower-extremity diabetic neurotrophic ulcers of at least 8 weeks' duration, free of necrotic and infected tissue after debridement, and with transcutaneous oxygen tensions of 30 mm Hg or greater were studied. A total of 118 patients were randomized to receive either topical rhPDGF-BB (2.2 μg/cm ² of ulcer area) or placebo until the ulcer was completely resurfaced or for a maximum of 20 weeks, whichever occurred first.Results: Twenty-nine (48%) of 61 patients randomized to the rhPDGF-BB group achieved complete wound healing during the study compared with only 14 (25%) of 57 patients randomized to the placebo group ( p = 0.01). The median reduction in wound area in the group given rhPDGF-BB was 98.8% compared with 82.1% in the group given placebo ( p = 0.09). There were no significant differences in the incidence or severity of adverse events between the rhPDGF-BB and placebo groups.Conclusions: Once-daily topical application of rhPDGF-BB is safe and effective in stimulating the healing of chronic, full-thickness, lower-extremity diabetic neurotrophic ulcers. (J VASC SURG 1995;21:71-81.)     

Off-loading of hindfoot and midfoot neuropathic ulcers using a fiberglass cast with a metal stirrup

BACKGROUND: This study was designed to assess the effectiveness of a method of off-loading large neuropathic ulcers of the hindfoot and midfoot. The device used is composed of a fiberglass cast with a metal stirrup and a window around the ulcer. METHODS: A retrospective study of 14 diabetic and nondiabetic patients was performed. All had chronic plantar hindfoot or midfoot neuropathic ulcers that failed to heal with conventional treatment methods. A fiberglass total contact cast with a metal stirrup was applied. A window was made over the ulcer to allow daily ulcer care. RESULTS: The average duration of ulcer before application of the metal stirrup was 26 + 13.2 (range 7 to 52) months. The ulcer completely healed in 12 of the 14 patients treated. The mean time for healing was 10.8 weeks for midfoot ulcers and 12.3 weeks for heel ulcers. Complications developed in four patients: three developed superficial wounds and one developed a full-thickness wound. In three of these four patients, local wound care was initiated, and the stirrup cast was continued to complete healing of the primary ulcer. CONCLUSIONS: A fiberglass cast with a metal stirrup is an effective off-loading device for midfoot and hindfoot ulcers. It is not removable and does not depend on patient compliance. The window around the ulcer allows for daily wound care, drainage of the ulcer and the use of vacuum-assisted closure (VAC) treatment. The complication rate is comparable to that of total contact casting.     

Wound outcomes in patients with advanced illness

A prospective case series was studied to assess the potential for complete healing of wounds among patients with advanced illness referred to a regional palliative care program in Toronto, Canada. Two hundred and eighty‐two patients, of which 148 were primarily diagnosed with cancer and 134 with non cancer advanced illness, were assessed and followed until their deaths. On the baseline initial referral date, 823 wounds were documented. The wound classes assessed included pressure ulcers, malignant wounds, skin tears, venous leg ulcers, diabetic foot ulcers and arterial leg/foot ulcers. Proportions of patients showing complete healing of at least one wound were calculated, stratified by patient's survival time post‐baseline (1 week, 1 month, 3 months and 6 months). Proportions of patients showing complete healing of at least one wound increased the longer patients lived and ranged between 12·9% and 43·5% for stage I pressure ulcers, 0% and 60% for stage II pressure ulcers, 2·4% and 100% for skin tears, 10% and 100% for venous leg ulcers and 0% and 50% for diabetic foot ulcers. Only one person showed complete healing of a stage III pressure ulcer and no complete healing was observed with stage IV pressure ulcers, unstageable pressure ulcers, malignant wounds and arterial leg/foot ulcers.     

Metatarsal head resection for diabetic foot ulcers

Twenty-five diabetic patients underwent 34 metatarsal head resections for chronic neuropathic ulceration. All ulcers were located on the plantar surface beneath the metatarsophalangeal joints. The ulcers had been present for a mean of 9.0 +/- 7.8 months before operation, yet they healed in a mean of 2.4 +/- 1.6 months postoperatively. None recurred during the mean follow-up time of 13.8 +/- 11.0 months. Moderate peripheral vascular disease, impaired renal function, and retinopathy did not affect the time required for ulcer healing. There were two complications: one wound infection and one hematoma. No extremities were lost, and none of the patients suffered any long-term sequelae. We recommend metatarsal head resection to achieve the healing of chronic diabetic foot ulcers under the metatarsophalangeal joints.     

Autologous fibroblasts to treat deep and complicated leg ulcers in diabetic patients

Large complicated leg ulcers, not responsive to standard therapy, after surgical debridement and under parenteral specific antibiosis, must be occlusively covered to improve wound healing. In 10 diabetic patients with deep (Wagner degree 3), large, and Staphylococcus aureus (n=7) or Pseudomonas aeruginosa (n=5)-infected leg (n=1), or foot (n=9) ulcers, we have applied, as a coverage, meshes of in vitro expanded autologous fibroblasts. Complete ulcer healing was observed in seven patients after 8, 12, 12, 14, 16, 18, and 20 weeks from the first graft application (Figures 2 and 3). Two patients had >70% wound healing at 20 and 28 weeks after the first treatment. One patient, previously submitted to a bypass vascular procedure, died of acute myocardial infarction 16 weeks after the first fibroblast autograft application and with a healing wound evenly filled with granulation tissue. In our opinion, the application of autologous in vitro expanded fibroblasts is a satisfactory therapeutic option to treat large leg ulcers and is particularly indicated in patients with chronic diseases such as diabetes or autoimmune diseases on steroid treatment.