Evaluation of tissue engineering products for the management of neuropathic diabetic foot ulcers: an interim analysis.

OBJECTIVE: The objective of this prospective, multicentre clinical study is to assess the application of MatriStem MicroMatrix (MSMM) and MatriStem Wound Matrix (MSWM) (porcine urinary bladder derived extracellular matrix) compared with Dermagraft (DG) (human fibroblast-derived dermal substitute) for the management of non-healing diabetic foot ulcers (DFUs). METHOD: A randomised, multicentre study was conducted at thirteen centers throughout the US. It was designed to evaluate the incidence of ulcer closure, rate of ulcer healing, wound characteristics, patient quality of life, cost-effectiveness, and recurrence. Those subjects whose DFUs decreased in size by ≤30% or increased by ≤50% during the standard of care (SOC) phase were randomised into the treatment phase of the study. The study evaluated complete wound closure by eight weeks with weekly device application. A two-week post treatment SOC phase followed the treatment phase for any wounds that did not heal by the end of eight weeks, and wound closure was also evaluated at the end of that period. Ulcer recurrence at 6 months post-treatment was evaluated in the subjects that showed wound healing by the end of the post-treatment SOC phase. Standard adjunctive therapy, including debridement, saline irrigation and foot off-loading, was provided to both arms during the four-week screening period, after which eligible subjects were randomised in a 1:1 ratio, to either the MatriStem (MS) or DG treatment arm. This study was developed to evaluate the hypothesis that the wound outcomes observed after wound management with MS were non-inferior to those of DG after eight weeks. The authors present the planned interim results of this study after one half of the projected enrolment was completed. RESULTS: There were 95 subjects consented and entered into the SOC four-week screening phase of the trial and 56 were randomised into the treatment phase. At the planned interim analysis, there was a significantly lower cost per subject and significant improvement in patient quality of life for the subjects treated with MS compared with those managed with DG. However, there was not a statistically significant difference found during the analysis of the interim data between the two study groups for rate of wound healing or number of subjects with complete wound closure. CONCLUSION: The data from this interim analysis show that MSMM and MSWM provide results for healing DFUs that are similar to the results obtained for DG at a significant quality of life and economic advantage. DECLARATION OF INTEREST: The opinions expressed are those of the authors and not necessarily those of the Department of Veterans Affairs or the United States Government. T.W. Gilbert is employed as the Chief Science Officer and is a stockholder in ACell, Inc., which commercializes MatriStem Wound Matrix and MicroMatrix. None of the other authors have a conflict of interest to declare.

Human acellular dermal wound matrix for treatment of DFU: literature review and analysis.

UNLABELLED: Diabetic foot ulcers (DFUs) affect a significant number of people and the treatment is challenging and costly. Since only a small portion of patients respond to standard care, the majority require more advanced wound healing interventions. Human acellular dermal matrices-regenerative tissue matrices derived from human tissue and processed from screened donated skin-can aid wound closure by restoring the missing physiological factors to the microenvironment. A literature review of the clinical literature was performed to estimate the comparative effectiveness of one specific human acellular dermal wound matrix (HADWM; Graftjacket regenerative tissue matrix) versus standard care in healing DFUs. Outcomes from three prospective, controlled clinical trials, which included 154 patients with DFUs, were pooled. A comparative analysis revealed a statistically significant reduction in mean wound healing time, 1.7 weeks, as well as a nearly four-fold improvement in the chance of healing ulcers treated with HADWM versus moist wound-care. These pooled results suggest that HADWM may improve healing outcomes for these difficult-to-heal lower extremity wounds. DECLARATION OF INTEREST: Alexander Reyzelman is a consultant for KCI, an Acelity company.

Effect of oral nutritional supplementation on wound healing in diabetic foot ulcers: a prospective randomized controlled trial.

AIMS: Among people with diabetes, 10-25% will experience a foot ulcer. Research has shown that supplementation with arginine, glutamine and ß-hydroxy-ß-methylbutyrate may improve wound repair. This study tested whether such supplementation would improve healing of foot ulcers in persons with diabetes. METHODS: Along with standard of care, 270 subjects received, in a double-blinded fashion, (twice per day) either arginine, glutamine and ß-hydroxy-ß-methylbutyrate or a control drink for 16 weeks. The proportion of subjects with total wound closure and time to complete healing was assessed. In a post-hoc analysis, the interaction of serum albumin or limb perfusion, as measured by ankle-brachial index, and supplementation on healing was investigated. RESULTS: Overall, there were no group differences in wound closure or time to wound healing at week 16. However, in subjects with an albumin level of ≤ 40 g/l and/or an ankle-brachial index of < 1.0, a significantly greater proportion of subjects in the arginine, glutamine and ß-hydroxy-ß-methylbutyrate group healed at week 16 compared with control subjects (P = 0.03 and 0.008, respectively). Those with low albumin or decreased limb perfusion in the supplementation group were 1.70 (95% CI 1.04-2.79) and 1.66 (95% CI 1.15-2.38) times more likely to heal. CONCLUSIONS: While no differences in healing were identified with supplementation in non-ischaemic patients or those with normal albumin, addition of arginine, glutamine and ß-hydroxy-ß-methylbutyrate as an adjunct to standard of care may improve healing of diabetic foot ulcers in patients with risk of poor limb perfusion and/or low albumin levels. Further investigation involving arginine, glutamine and ß-hydroxy-ß-methylbutyrate in these high-risk subgroups might prove clinically valuable.

Are antibiotics necessary in the treatment of locally infected ingrown toenails?

CONTEXT: A wide variety of generalists and specialists treat locally infected ingrown toenails, with perhaps the most common treatment regimen including resection of the nail border coupled with oral antibiotics. OBJECTIVE: To determine whether oral antibiotic therapy is beneficial as an adjunct to the phenol chemical matrixectomy in the treatment of infected ingrown toenails. DESIGN: We prospectively enrolled healthy patients with infected ingrown toenails. Each patient was randomly assigned to 1 of 3 groups that received either 1 week of antibiotics and a chemical matrixectomy simultaneously (group 1), antibiotics for 1 week and then a matrixectomy (group 2), or a matrixectomy alone (group 3). SETTING: Institutional ambulatory outpatient clinic. PATIENTS: Fifty-four healthy patients with infected ingrown toenails were studied. Patients with immunocompromised states, peripheral vascular disease, or cellulitis proximal to the hallux interphalangeal joint were excluded. Groups were age matched for comparison. RESULTS: Mean healing times for groups 1, 2, and 3 were 1.9, 2.3, and 2.0 weeks, respectively. Subjects receiving antibiotics and a simultaneous chemical matrixectomy (group 1) healed significantly sooner than those receiving a 1-week course of antibiotics followed by a matrixectomy (group 2). There was not a significant difference in healing time between those that received a chemical matrixectomy alone (group 3) and those that received a matrixectomy coupled with a course of oral antibiotics (group 1). CONCLUSION: The use of oral antibiotics as an adjunctive therapy in treating ingrown toenails does not play a role in decreasing the healing time or postprocedure morbidity.

The increased prevalence of severe necrotizing infections caused by non-group A streptococci.

The authors report on 20 patients who were admitted to the University of Texas Health Science Center at San Antonio during a recent 4-month period with foot infections caused predominantly by non-group A streptococci. This number of patients was significantly greater than the number admitted to the same institution with the same diagnosis during the preceding 3 years. All patients had type 2 diabetes mellitus. In each case, a rapidly spreading cellulitis followed trauma to the foot, which necessitated emergent incision and drainage. Five patients required extensive fascial and skin debridement because of soft-tissue destruction, and two patients needed below-the-knee amputation because of uncontrolled infection. These cases suggest that non-group A streptococci, like group A streptococci, can cause serious skin and soft-tissue infections in patients with diabetes that may require aggressive surgical debridement despite appropriate antibiotic therapy.

Limb salvage with Chopart's amputation and tendon balancing.

For several decades, Chopart's amputation has met with some skepticism owing to reports of significant equinus deformity developing soon after the procedure is performed. However, with appropriate tendon balancing, which generally includes anterior tibial tendon transfer and tendo Achillis lengthening, this level of amputation is often more functional than slightly more distal amputations, such as Lisfranc or short transmetatarsal amputations. The authors offer a rationale for this observation, which includes a discussion of the longitudinal and transverse arch concept of the foot. This concept dictates that the shorter the midfoot-level amputation, the more likely the patient is to develop an equinovarus deformity, thus exposing the fifth metatarsal base and cuboid to weightbearing stress and a high risk of ulceration. Chopart's amputation, in eliminating the cuboid, often obviates the potential varus deformity and thus can have a more acceptable long-term result.

Preoperative assessment of the transplant patient.

In the authors' university medical center, there are an increasing number of transplant patients presenting for foot surgery. Newer immunosuppressive agents are largely responsible for improvement of graft and patient survival and hence more patients requiring and wanting foot surgery. Podiatric surgeons must approach these patients with caution, but not fear. Transplant patients are more susceptible to infection, have altered response to stress from surgery, and may have delayed wound healing. Preoperative assessment and planning are imperative when considering surgery for transplant patients.

Emergence of non-group A streptococcal necrotizing diabetic foot infections.

Recently the authors have noted a disturbing trend toward an increased incidence of necrotizing infections caused by non-group A streptococcal species. This article describes the typical clinical course of such an infection. Prompt surgical intervention, coupled with an antibiotic regimen aimed at mitigating exotoxin release, may be both limb- and life-preserving.

Evaluation and management of the interdigital corn: a literature review.

Interdigital corns or soft corns are the accumulation of spongy, hyperkeratotic, circumscribed tissue between opposing surfaces of adjacent digits of the foot. The authors discuss the incidence, causes, locations, and treatment of these interdigital corns.