Impact of Synthetic Extracellular Matrices in Combination Therapy with Amniotic Allografting in the Treatment of Diabetic Foot Wounds: A Case Series.

Synthetic extracellular matrices are artificial polymers that are elongated and deposited as a matrix of nanofibers which mimic the native extracellular matrix. RenovoDerm® Anthem™ Wound Matrix (Columbus, Ohio) is comprised of polyglycolic acid and poly (L-lactide-co-caprolactone) which degrade by hydrolysis into a-hydroxy and fatty acids, lowering the pH and promoting regenerative cellular activity including angiogenesis. Amniotic allografts contain growth factors, cytokines, amino acids, extracellular matrix proteins, and hyaluronic acid which are recognized as intrinsic to the wound healing process. Synthetic extracellular matrices alone or in combination with amnio allografts do not have large bodies of evidence which demonstrate their effectiveness in the treatment of wounds. Presently, no prior studies have been performed to assess what impact these therapies may have on wound healing when used concurrently. The aim of this investigation was to assess whether a synergistic effect is produced with combination therapy using synthetic extracellular matrix and amniotic allografting. In this article, we present four cases of diabetic foot ulcerations treated with combination therapy. An amniotic fluid allograft, and/or membrane amniotic allograft, was implanted with a synthetic extracellular matrix dressing over top of the graft(s) at weekly intervals. All wounds demonstrated a greater than 80% decrease in wound size within four applications and achieved more than 95% wound closure after six applications.

A randomized clinical trial of a human acellular dermal matrix demonstrated superior healing rates for chronic diabetic foot ulcers over conventional care and an active acellular dermal matrix comparator.

This study compared the efficacy and safety of a human acellular dermal matrix (ADM), D-ADM, with a conventional care arm and an active comparator human ADM arm, GJ-ADM, for the treatment of chronic diabetic foot ulcers. The study design was a prospective, randomized controlled trial that enrolled 168 diabetic foot ulcer subjects in 13 centers across 9 states. Subjects in the ADM arms received one application but could receive one additional application of ADM if deemed necessary. Screen failures and early withdrawals left 53 subjects in the D-ADM arm, 56 in the conventional care arm, and 23 in the GJ-ADM arm (2:2:1 ratio). Subjects were followed through 24 weeks with major endpoints at Weeks 12, 16, and 24. Single application D-ADM subjects showed significantly greater wound closure rates than conventional care at all three endpoints while all applications D-ADM displayed a significantly higher healing rate than conventional care at Week 16 and Week 24. GJ-ADM did not show a significantly greater healing rate over conventional care at any of these time points. A blinded, third party adjudicator analyzed healing at Week 12 and expressed "strong" agreement (κ = 0.837). Closed ulcers in the single application D-ADM arm remained healed at a significantly greater rate than the conventional care arm at 4 weeks posttermination (100% vs. 86.7%; p = 0.0435). There was no significant difference between GJ-ADM and conventional care for healed wounds remaining closed. Single application D-ADM demonstrated significantly greater average percent wound area reduction than conventional care for Weeks 2-24 while single application GJ-ADM showed significantly greater wound area reduction over conventional care for Weeks 4-6, 9, and 11-12. D-ADM demonstrated significantly greater wound healing, larger wound area reduction, and a better capability of keeping healed wounds closed than conventional care in the treatment of chronic DFUs.

A prospective, multicentre, open-label, single-arm clinical trial for treatment of chronic complex diabetic foot wounds with exposed tendon and/or bone: positive clinical outcomes of viable cryopreserved human placental membrane.

Complex diabetic foot ulcers (DFUs) with exposed tendon or bone remain a challenge. They are more susceptible to complications such as infection and amputation and require treatments that promote rapid development of granulation tissue and, ultimately, reepithelialisation. The clinical effectiveness of viable cryopreserved human placental membrane (vCHPM) for DFUs has been established in a level 1 trial. However, complex wounds with exposed deeper structures are typically excluded from randomised controlled clinical trials despite being common in clinical practice. We report the results of a prospective, multicentre, open-label, single-arm clinical trial to establish clinical outcomes when vCHPM is applied weekly to complex DFUs with exposed deep structures. Patients with type 1 or type 2 diabetes and a complex DFU extending through the dermis with evidence of exposed muscle, tendon, fascia, bone and/or joint capsule were eligible for inclusion. Of the 31 patients enrolled, 27 completed the study. The mean wound area was 14·6 cm2 , and mean duration was 7·5 months. For patients completing the protocol, the primary endpoint, 100% wound granulation by week 16, was met by 96·3% of patients in a mean of 6·8 weeks. Complete wound closure occurred in 59·3% (mean 9·1 weeks). The 4-week percent area reduction was 54·3%. There were no product-related adverse events. Four patients (13%) withdrew, two (6·5%) for non-compliance and two (6·5%) for surgical intervention.

Ewing sarcoma in a diabetic male with history of foot ulceration.

Ewing sarcoma is a rare diagnosis, with as few as 225 new cases diagnosed in North America annually, and only 3% occurring in the foot. They generally present in the second decade of life and are very infrequently found in patients older than 40 years. The diagnosis of Ewing sarcoma can be difficult, especially in older patients with diabetes and a history of ulceration, because it can have an appearance on radiography similar to that of osteomyelitis. We present a case of Ewing sarcoma of the foot in a patient with type 2 diabetes in his sixth decade of life.

The impact and outcomes of establishing an integrated interdisciplinary surgical team to care for the diabetic foot.

OBJECTIVE: This study aimed to quantify the impact of an integrated diabetic foot surgical service on outcomes and changes in surgical volume and focus. METHODS: We abstracted registry data from 48 consecutive months at a single institution, evaluating all patients with diabetic foot complications requiring surgery or vascular intervention, and compared outcomes in the 24 months before and after integrating podiatric surgery with vascular surgical limb-salvage service. RESULTS: The service performed 2923 operations; 790 (27.0%) were related to treatment of diabetic foot complications in 374 patients. Of these, 502 were classified as non-vascular diabetic foot surgery and 288 were vascular interventions. Urgent surgery was significantly reduced after team implementation (77.7% vs 48.5%, p < 0.0001; OR = 3.7, 95% CI: 2.4-5.5). The high/low amputation ratio decreased from 0.35 to 0.27 due to an increase in low-level (midfoot) amputations (8.2% vs 26.1%, p < 0.0001; OR = 4.0, 95% CI: 2.0-83.3). A 45.7% reduction in below-knee amputations was realized with a stable above-knee/below-knee amputation ratio (0.73-0.81). One-third of patients required vascular intervention. Vascular reconstructions increased 44.1% following institution of the team. Initial revascularization was endovascular in 70.6% of patients. Repeat endovascular intervention or conversion to open bypass was required in 37.1% of these patients, almost double the reintervention rate of those receiving open bypass first (18.9%). CONCLUSIONS: Interdisciplinary diabetic foot surgery teams may significantly impact surgery type, with greater focus on proactive and preventive, rather than reactive and ablative, procedures. Although endovascular limb-sparing procedures have become increasingly applicable, open bypass remains critical to success.

Remote Temperature Monitoring in Patients With Visual Impairment Due to Diabetes Mellitus: A Proposed Improvement to Current Standard of Care for Prevention of Diabetic Foot Ulcers.

BACKGROUND: Two debilitating sequelae of diabetes are foot ulcerations and vision impairing conditions including retinopathy, open-angle glaucoma, and cataracts. Current standard of care recommends daily visual screening of feet. Despite willingness, many patients are impeded by visual impairment. We investigate whether once-daily remote temperature monitoring can improve self-screening for patients at risk for diabetic foot complications. METHODS: We followed four male veterans with diabetes mellitus, peripheral neuropathy, impaired visual acuity, and at least one other diabetes-related visual impairment in a high-risk podiatry clinic. Patients received a telemedicine remote temperature monitoring mat and instructed on proper daily use. Each patient developed a "hotspot," defined as a 1.75°C localized temperature difference between matched pedal locations, which resulted in telephone triage outreach. RESULTS: In three cases, outreach resulted in a sooner appointment where patients were found to have a relevant outcome at the hotspot. Patients in cases 1-3 had University of Texas (UT) 1A ulcerations. The patient in case 4 had inflammation from trauma. All patients had refractive errors plus another vision impairing condition that potentially delayed identification of lesions. Patients in cases 1 and 2 have cataracts, patients in cases 2 and 3 have retinopathy, and patient in case 4 has glaucoma. CONCLUSIONS: As an adjunct to daily preventative diabetic self-care, once-daily remote temperature monitoring technology can augment self-screening to prompt necessary outreach and treatment and potentially prevent costly and debilitating diabetic foot complications. This case series serves as a pilot study for real-world application of thermometry, where further large-scale research is needed.

Economic benefit of a novel dual-mode ambulatory compression device for treatment of chronic venous leg ulcers in a randomized clinical trial.

BACKGROUND: Limb compression is a key component of protocols used to heal venous leg ulcers (VLUs). A novel ambulatory pneumatic compression device was tested in comparison with multilayered bandage (MLB) compression systems for the treatment of VLUs in a prospective randomized clinical trial. METHODS: Patients with VLUs measuring 1.5 to 50 cm2 with duration of 1 to 24 months were randomized to treatment with a pneumatic compression device, the ACTitouch adaptive compression therapy (ACT) system (Tactile Medical, Minneapolis, Minn), or MLB. The ACT group patients were seen in the clinic at weeks 1, 2, 4, 6, 9, 12, and 16 or until wounds healed; the MLB group was seen weekly for bandage and dressing changes for 16 weeks or until wounds healed. All other aspects of VLU care were standardized between the two groups. The primary study objective was to compare the VLU percentage area reduction at 16 weeks in the ACT group compared with the MLB group. RESULTS: There were 56 patients randomized to treatment with ACT (n = 26) or MLB (n = 30). In the ACT group, five patients exited because of skin or wound problems related to the ACT device and five withdrew because of the inconvenience of using the device. Therefore, the trial was halted before full randomization so improvements to the ACT device could be made. Data collected on 42 patients who were able to tolerate treatment for the 16-week study period (per protocol group) showed that both groups experienced similar rates of wound healing. In the per protocol population, the percentage area size reduction was greater for the ACT group compared with the MLB group (83.8% vs 70.5%, respectively), whereas no significant differences were noted in the percentage of wounds that healed by 16 weeks (60.0% vs 63.0%, respectively). CONCLUSIONS: In this truncated clinical trial, a novel dual-mode ambulatory compression device, when tolerated, achieved wound healing results similar to those with MLB for chronic VLUs. The device requires modifications to improve the patient's comfort and ease of use. However, this mode of therapy appears to have promise for improving the cost-effectiveness of treatment for chronic VLUs.

Remote Temperature Monitoring in Diabetic Foot Ulcer Detection.

INTRODUCTION: Diabetic foot ulcers (DFUs) are associated with increased morbidity, mortality, and resource utilization. Remote temperature monitoring (RTM) is an evidence-based and recommended component of standard preventative foot care for high-risk populations that can detect the inflammation preceding and accompanying DFUs. OBJECTIVE: This case series illustrates the use of a RTM foot mat for the early detection and prevention of DFUs in patients with a history of DFUs. MATERIALS AND METHODS: Three patients with a history of diabetes, neuropathy, and DFUs were provided a RTM foot mat and instructed in its daily use. Persistent localized temperature differences exceeding 1.75˚C between the left and right feet prompted the clinical staff to call the patient to collect subjective history for further triage. RESULTS: Each patient presented with persistent temperature differences exceeding 1.75˚C. In one case, the patient was instructed to offload, and during a subsequent clinical exam, a callus was debrided and accommodative insoles were issued, resulting in resolution of the temperature differences. In the other 2 cases, the RTM foot mat prompted communication with and examination of the patient when there was damaged tissue deep to callus, resulting in early detection and treatment of uninfected DFUs. CONCLUSIONS: The findings of this case series are consistent with literature supporting the use of RTM for high-risk patients.

Fully Synthetic Bioengineered Nanomedical Scaffold in Chronic Neuropathic Foot Ulcers.

INTRODUCTION: Chronic ulcerations on weightbearing surfaces of the lower extremities are uniquely challenging and can lead to complications such as infection or amputation. OBJECTIVE: This 3-patient case series of 4 chronic wounds of various etiologies outlines the use of a fully synthetic bioengineered nanomedical scaffold that exhibits durability and allows for cell migration and angiogenesis while resisting enzymatic degradation. MATERIALS AND METHODS: The nanomedical scaffold was rehydrated in sterile saline at room temperature for 3 to 5 minutes until translucent and pliable, then it was fenestrated with a scalpel. Following sharp debridement, it was affixed to the ulcer. A nonadherent dressing was applied, followed by applying a moist sterile dressing in a bolster fashion. RESULTS: All 4 ulcers reached the primary endpoints of granulation, as well as decreased wound size, using the nanomedical scaffold. CONCLUSIONS: The nanomedical scaffold successfully reduced the ulcer depths, stimulated granulation tissue while preventing necrosis, and helped the wounds remain infection free. The outcome of this case series suggests a fully synthetic bioengineered nanomedical scaffold can be used as an alternative to human or animal extracellular matrix in chronic, hard-to-heal neuropathic ulcers.

Randomized Controlled Trial of Micronized Dehydrated Human Amnion/Chorion Membrane (dHACM) Injection Compared to Placebo for the Treatment of Plantar Fasciitis.

BACKGROUND: Failure of conservative management to reduce/eliminate symptoms of plantar fasciitis (PF) may indicate need for advanced treatments. This study reports Level 1 evidence supporting 3-month safety and efficacy of micronized dehydrated human amnion/chorion membrane (dHACM) injection as a treatment for PF. METHODS: A prospective, single-blind, randomized controlled trial was conducted at 14 sites in the United States. Subjects were randomized to receive 1 injection, in the affected area, of micronized dHACM (n=73) or 0.9% sodium chloride placebo (n=72). Safety/efficacy assessments were conducted at 4 weeks, 8 weeks, 3 months, 6 months, and 12 months postinjection, using visual analog scale (VAS) for pain, Foot Function Index-Revised (FFI-R) score, and presence/absence of adverse events. Primary outcome was mean change in VAS score between baseline and 3 months expressed as difference in means for treatment versus control subjects. Secondary outcome was mean change in FFI-R score between baseline and 3 months expressed as difference in means for treatment versus control subjects. RESULTS: Baseline VAS scores were similar between groups. At the 3-month follow-up, mean VAS scores in the treatment group were 76% lower compared with a 45% reduction for controls ( P < .0001), FFI-R scores for treatment subjects had mean reduction of 60% versus baseline, whereas control subjects had mean reduction of 40% versus baseline ( P = .0004). Of 4 serious adverse events, none were related to study procedures. CONCLUSION: Pain reduction and functional improvement outcomes were statistically significant and clinically relevant, supporting use of micronized dHACM injection as a safe and effective treatment for PF. LEVEL OF EVIDENCE: Level I, prospective randomized trial.

Diabetic foot infections in the elderly: primary amputation versus 'foot-sparing surgery'. A case report.

Renal failure diabetic patients who present with lower extremity gangrene represent one of the most difficult problems encountered in a typical vascular practice. We report the hospital course and management of a 74-year-old male patient with such comorbidities, affected by a non healing ulcer that progressed into a large plantar abscess. Our case unfortunately mirrors a common method of evaluation and therapy of patients with such comorbidities and sets up the stage for a very controversial subject.

Healing Rates in a Multicenter Assessment of a Sterile, Room Temperature, Acellular Dermal Matrix Versus Conventional Care Wound Management and an Active Comparator in the Treatment of Full-Thickness Diabetic Foot Ulcers.

OBJECTIVE: The purpose of this 16-week, multicenter, randomized, controlled trial was to assess the healed ulcer rate of a human acellular dermal matrix, DermACELL, compared with conventional care and a second acellular dermal matrix, Graftjacket, in the treatment of full-thickness diabetic foot ulcers. METHODS: One hundred sixty-eight patients were randomized into DermACELL, conventional care, and Graftjacket treatment arms in a 2:2:1 ratio. Patients in the acellular dermal matrix groups received either 1 or 2 applications of the graft at the discretion of the investigator. Weekly follow-up visits were conducted until the ulcer healed or the endpoint was reached. RESULTS: At 16 weeks, the DermACELL arm had a significantly higher proportion of completely healed ulcers than the conventional care arm (67.9% vs 48.1%; P = .0385) and a nonsignificantly higher proportion than the Graftjacket arm (67.9% vs 47.8%; P = .1149). The DermACELL arm also exhibited a greater average percent reduction in wound area than the conventional care arm (91.4% vs 80.3%; P = .0791) and the Graftjacket arm (91.4% vs 73.5%; P = .0762). The proportion of severe adverse events and the proportion of overall early withdrawals were similar among the 3 groups based on relative population size (P ≥ .05). CONCLUSIONS: The results presented here indicate that DermACELL is an appropriate clinical option in the treatment of diabetic foot ulcers, with significant increases in healing rates and rate of percentage wound closure as compared with conventional care options.

Group B and F Beta Streptococcus Necrotizing Infection-Surgical Challenges with a Deep Central Plantar Space Abscess A Diabetic Limb Salvage Case Report.

We present the case of a 66-year-old, type II diabetic male with a deep wound to the plantar-lateral aspect of his right hallux. On examination, the central plantar compartment of his right foot was moderately erythematous and tender on palpation. After obtaining a deep wound culture, treatment was complicated by a progression of a group B and F beta streptococcus, necrotizing infection. The patient underwent a right hallux amputation, followed by a plantar medial incision for drainage of an abscess to the medial and central plantar compartments of the foot. Due to the extent and limb threat of the infection, the patient ultimately underwent a transmetatarsal amputation. Advanced healing modalities were also employed to decrease wound healing times, which allowed the patient to achieve early weightbearing and return to activities of daily living. This study depicts how the astute podiatric surgeon needs to make a decision in a timely manner to surgically debride all nonviable and necrotic tissue in order to minimize further amputation and preserve foot function.

Group B and F Beta Streptococcus Necrotizing Infection-Surgical Challenges with a Deep Central Plantar Space Abscess: A Diabetic Limb Salvage Case Report.

We present the case of a 66-year-old, type II diabetic male with a deep wound to the plantar-lateral aspect of his right hallux. On examination, the central plantar compartment of his right foot was moderately erythematous and tender on palpation. After obtaining a deep wound culture, treatment was complicated by a progression of a group B and F beta streptococcus, necrotizing infection. The patient underwent a right hallux amputation, followed by a plantar medial incision for drainage of an abscess to the medial and central plantar compartments of the foot. Due to the extent and limb threat of the infection, the patient ultimately underwent a transmetatarsal amputation. Advanced healing modalities were also employed to decrease wound healing times, which allowed the patient to achieve early weightbearing and return to activities of daily living. This study depicts how the astute podiatric surgeon needs to make a decision in a timely manner to surgically debride all nonviable and necrotic tissue in order to minimize further amputation and preserve foot function.

Feasibility, safety, and primary efficacy of DermaStream: a novel continuously streaming device for chronic wounds.

Chronic wounds are associated with significant morbidity, mortality, and economic burden. Once a wound has settled into a senescent phase, outside factors must be used to convert that wound back to a more acute phase. Traditional methods, such as surgical debridement or biologic debridement, can cause removal of healthy tissue as well as pain to the patient. Enzymatic debridement has been under much scrutiny lately as popular drugs have been pulled by the Food and Drug Administration. The purpose of this study was to test feasibility, safety, and primary efficacy of 5 control subjects and 10 treatment subjects to the DermaStream system. It is a device that uses a continuously streaming infusion to create a stable, granular wound bed in a relatively short amount of time. The device provides for continuously streaming of therapeutic solutions to the wound while removing exudates by vacuum-assisted drainage throughout the treatment cycle.

Comparison of negative pressure wound therapy using vacuum-assisted closure with advanced moist wound therapy in the treatment of diabetic foot ulcers: a multicenter randomized controlled trial.

OBJECTIVE: The purpose of this study was to evaluate safety and clinical efficacy of negative pressure wound therapy (NPWT) compared with advanced moist wound therapy (AMWT) to treat foot ulcers in diabetic patients. RESEARCH DESIGN AND METHODS: This multicenter randomized controlled trial enrolled 342 patients with a mean age of 58 years; 79% were male. Complete ulcer closure was defined as skin closure (100% reepithelization) without drainage or dressing requirements. Patients were randomly assigned to either NPWT (vacuum-assisted closure) or AMWT (predominately hydrogels and alginates) and received standard off-loading therapy as needed. The trial evaluated treatment until day 112 or ulcer closure by any means. Patients whose wounds achieved ulcer closure were followed at 3 and 9 months. Each study visit included closure assessment by wound examination and tracings. RESULTS: A greater proportion of foot ulcers achieved complete ulcer closure with NPWT (73 of 169, 43.2%) than with AMWT (48 of 166, 28.9%) within the 112-day active treatment phase (P = 0.007). The Kaplan-Meier median estimate for 100% ulcer closure was 96 days (95% CI 75.0-114.0) for NPWT and not determinable for AMWT (P = 0.001). NPWT patients experienced significantly (P = 0.035) fewer secondary amputations. The proportion of home care therapy days to total therapy days for NPWT was 9,471 of 10,579 (89.5%) and 12,210 of 12,810 (95.3%) for AMWT. In assessing safety, no significant difference between the groups was observed in treatment-related complications such as infection, cellulitis, and osteomyelitis at 6 months. CONCLUSIONS: NPWT appears to be as safe as and more efficacious than AMWT for the treatment of diabetic foot ulcers.