Outcomes of Partial Calcanectomy in an Academic Limb Salvage Center: A Multicenter Review.

Chronic nonhealing heel ulcerations have been established as an independent risk factor for major amputation, with poor rates of limb salvage success. Partial calcanectomy is a controversial limb salvage procedure reserved for patients with these heel ulcerations. We conducted a retrospective cohort study reviewing 39 limbs that underwent a partial calcanectomy from 2012 to 2018 to evaluate the proportion of patients healed, time to healing, ulcer recurrence, and postoperative functional level compared to the preoperative state. In addition, age, gender, body mass index, smoking status, coronary artery disease, diabetes mellitus, renal insufficiency, dialysis, peripheral arterial disease, method of closure, and percent of calcaneus resected were evaluated. Mean follow-up for our cohort was 2.3 years. We had a 1 year mortality rate of 11%, and a major amputation rate of 18%. Our results demonstrated a 77% healing rate with a median time to healing of 162 days. We found that patients who were closed primarily had a faster time to healing compared to patients who underwent closure by secondary intention. Our data showed that ulcer recurrence developed in 57% of healed limbs. We found that 76% of our patients were ambulatory postoperatively. These results suggest that partial calcanectomy is a viable limb salvage procedure with a predictable level of ambulation and function in a high-risk patient population.

Gene therapy for diabetic foot ulcers: Interim analysis of a randomised, placebo-controlled phase 3 study of VM202 (ENGENSIS), a plasmid DNA expressing two isoforms of human hepatocyte growth factor.

To evaluate the status of a 7-month phase 3 study conducted to test the effect of intramuscular injections of VM202 (ENGENSIS), a plasmid DNA encoding human hepatocyte growth factor, into the calf muscles of chronic nonhealing diabetic foot ulcers with concomitant peripheral artery disease. The phase 3 study, originally aimed to recruit 300 subjects, was discontinued because of slow patient recruitment. An unprespecified interim analysis was performed for the 44 subjects enrolled to assess the status and determine the future direction. Statistical analyses were carried out for the Intent-to-Treat (ITT) population and separately for subjects with neuroischemic ulcers, using a t-test and Fisher's exact test. A logistic regression analysis was also conducted. VM202 was safe and potentially should have benefits. In the ITT population (N = 44), there was a positive trend toward closure in the VM202 group from 3 to 6 months but with no statistical significance. Levels of ulcer volume or area were found to be highly skewed between the placebo and VM202 groups. Forty subjects, excluding four outliers in both arms, showed significant wound-closing effects at month 6 (P = .0457). In 23 patients with neuroischemic ulcers, the percentage of subjects reaching complete ulcer closure was significantly higher in the VM202 group at months 3, 4, and 5 (P = .0391, .0391, and .0361). When two outliers were excluded, a significant difference was evident in months 3, 4, 5, and 6 (P = .03 for all points). A potentially clinically meaningful 0.15 increase in Ankle-Brachial Index was observed in the VM202 group at day 210 in the ITT population (P = .0776). Intramuscular injections of VM202 plasmid DNA to calf muscle may have promise in the treatment of chronic neuroischemic diabetic foot ulcers (DFUs). Given the safety profile and potential healing effects, continuing a larger DFU study is warranted with modifications of the current protocol and expansion of enrolling sites.

Phase 3 evaluation of HP802-247 in the treatment of chronic venous leg ulcers.

In 2012 we reported promising results from a phase 2 clinical trial of HP802-247, a novel spray-applied investigational treatment for chronic venous leg ulcers consisting of human, allogeneic fibroblasts and keratinocytes. We now describe phase 3 clinical testing of HP802-247, its failure to detect efficacy, and subsequent investigation into the root causes of the failure. Two randomized, controlled trials enrolled a total of 673 adult outpatients at 96 centers in North America and Europe. The primary endpoint was the proportion of ulcers with confirmed closure at the end of 12 weeks of treatment. An investigation into the root cause for the failure of HP802-247 to show efficacy in these two phase 3 trials was initiated immediately following the initial review of the North American trial results. Four hundred twenty-one patients were enrolled in the North American (HP802-247, 211; Vehicle 210) and 252 in the European (HP802-247, 131; Vehicle 121) trials. No difference in proportion of closed ulcers at week 12 was observed between treatment groups for either the North American (HP802-247, 61.1%; Vehicle 60.0%; p = 0.5896) or the European (HP802-247, 47.0%; Vehicle 50.0%; p = 0.5348) trials. Thorough investigation found no likelihood that design or execution of the trials contributed to the failure. Variability over time during the trials in the clinical response implicated the quality of the cells comprising HP802-247. Concordance between the two separate, randomized, controlled trials with distinct, nonoverlapping investigative sites and independent monitoring teams renders the possibility of a Type II error vanishingly small and provides strong credibility for the unexpected lack of efficacy observed. The most likely causative factors for the efficacy failure in phase 3 was phenotypic change in the cells (primarily keratinocytes) leading to batch to batch variability due to the age of the cell banks.

Achilles Tendon Rupture Repair: Simple to Complex.

There are many factors to consider when treating an Achilles tendon rupture in the acute and chronic/neglected settings. For acute rupture, operative and nonoperative management contribute to a good prognosis with low associated risks. Patient or injury characteristics can assist in the shared decision-making about treatment. In chronic rupture, MRI may help to determine rupture location, gap distance, and tissue material available for repair. Various surgical approaches are used for chronic rupture repair. Treatment of the Achilles tendon rupture generates many interesting and complex discussions on the optimal management.

A Prospective, Single-center, Open-label Case Series Evaluating the Clinical Outcomes of Lyopreserved Placental Membrane Containing Viable Cells in the Treatment of Chronic Wounds.

INTRODUCTION: Cryopreserved placental membrane containing viable cells (vCPM) in conjunction with standard of care (SOC) has shown clinical effectiveness in several studies for the management of acute and chronic wounds. Recently, a new lyophilization technique has been developed that allows viable tissues to be stored at room temperature as a structural and functional equivalent to vCPM. OBJECTIVE: This case series evaluates the clinical outcomes of a lyopreserved placental membrane containing viable cells (vLPM) for the management of chronic wounds of various etiologies. MATERIALS AND METHODS: Eleven patients (11 wounds: 5 diabetic foot ulcers, 5 venous leg ulcers, and 1 pressure ulcer) received weekly vLPM applications adjunct to SOC. RESULTS: By week 12 of treatment, 63.6% (7/11) of patients achieved complete wound closure, with a mean time to closure of 47.1 days and a mean of 6 vLPM applications. Further, there were no adverse events attributed to vLPM. CONCLUSIONS: This is the first case series reporting the clinical outcomes of vLPM for the management of chronic wounds. Results of this study demonstrate similar closure rates to those previously reported for vCPM. These results suggest potential clinical equivalence between the 2 formulations, with vLPM providing the added convenience of long-term room-temperature storage (current shelf life of 12 months).

Initial Report on the Use of In-Office Cone Beam Computed Tomography for Early Diagnosis of Osteomyelitis in Diabetic Patients.

Osteomyelitis is one of the most feared sequelae of diabetic foot ulceration, which often leads to lower-extremity amputation and disability. Early diagnosis of osteomyelitis increases the likelihood of successful treatment and may limit the amount of bone resected, preserving ambulatory function. Although a variety of techniques exist for imaging the diabetic foot, standard radiography is still the only in-office imaging modality used today. However, radiographs lack sensitivity and specificity, making it difficult to diagnose bone infection at its early stages. In this report, we describe our initial experience with a cone beam computed tomography (CBCT)-based device, which may serve as an accurate and readily available tool for early diagnosis of osteomyelitis in a patient with diabetes. Two patients with infected diabetic foot ulcers were evaluated for osteomyelitis using radiography and CBCT. Positive imaging findings were confirmed by bone biopsy. In both patients, CBCT captured early osteolytic changes that were not apparent on radiographs, leading to early surgical intervention and successful treatment. The CBCT was helpful in facilitating detection and early clinical intervention for osteomyelitis in two diabetic patients with foot ulcers. These results are encouraging and warrant future evaluation.

Evidence of Intensive Autolytic Debridement With a Self-Adaptive Wound Dressing.

BACKGROUND: Chronic venous leg ulcers (VLUs) can be challenging to manage and heal. Despite the observed efficacy of surgical debridement, many patients with VLUs refuse the procedure due to the associated pain. Autolytic debridement induces no pain, but is slow or disrupted in chronic VLUs. Elucidation of the wound dressing functions that are sufficient to support autolytic debridement is needed. MATERIALS AND METHODS: The authors report 2 challenging cases with large, nonresponsive VLUs. A 52-year-old female patient, Case 1, presented with a VLU of 91.4 cm(2) (10.5 cm x 8.7 cm); and a 58-year-old female patient, Case 2, presented with bilateral VLUs, the larger of which was 50 cm(2) (10 cm x 5 cm). Both VLU cases were covered with yellow slough, and case 1 had a small area of black necrotic tissue. The patients had received standard care for more than 16 months, but their VLUs were worsening. A self-adaptive wound dressing (SAWD) with a compression wrap was applied 2 to 3 times a week. RESULTS: Within 21 days, the VLUs of both cases had shed the yellow slough, and healthy granulation tissue was visible. CONCLUSION: In summary, the SAWD removed excess exudate with liquefied components of slough and nonvital tissue; provided sufficient moisture for preventing wound desiccation; sequestered microorganisms, thereby blocking their multiplication; and supported efficient autolytic debridement, clearing most of the slough and all crusted necrotic tissue within 3 weeks. The effect of SAWD on autolytic debridement is a promising mechanism for promoting healing of VLUs and warrants further study.

Subtalar arthroereisis and its role in pediatric and adult population.

Subtalar joint arthroereisis is a surgical procedure that addresses symptomatic flexible flatfoot deformities using an extraarticular implant within the sinus tarsi. Three groups of implants have been developed for this procedure: self-locking wedges, axis-altering devices, and impact-blocking devices. The self-locking wedge implants are the focus of this article, relative to its use, limitations, and controversies in the pediatric and adult population.