A purified reconstituted bilayer matrix shows improved outcomes in treatment of non-healing diabetic foot ulcers when compared to the standard of care: Final results and analysis of a prospective, randomized, controlled, multi-centre clinical trial.

As the incidence of diabetic foot ulcers (DFU) increases, better treatments that improve healing should reduce complications of these ulcers including infections and amputations. We conducted a randomized controlled trial comparing outcomes between a novel purified reconstituted bilayer membrane (PRBM) to the standard of care (SOC) in the treatment of non-healing DFUs. This study included 105 patients who were randomized to either of two treatment groups (n = 54 PRBM; n = 51 SOC) in the intent to treat (ITT) group and 80 who completed the study per protocol (PP) (n = 47 PRBM; n = 33 SOC). The primary endpoint was the percentage of wounds closed after 12 weeks. Secondary outcomes included percent area reduction, time to healing, quality of life, and cost to closure. The DFUs that had been treated with PRBM healed at a higher rate than those treated with SOC (ITT: 83% vs. 45%, p = 0.00004, PP: 92% vs. 67%, p = 0.005). Wounds treated with PRBM also healed significantly faster than those treated with SOC with a mean of 42 versus 62 days for SOC (p = 0.00074) and achieved a mean wound area reduction within 12 weeks of 94% versus 51% for SOC (p = 0.0023). There were no adverse events or serious adverse events that were related to either the PRBM or the SOC. In comparison to the SOC, DFUs healed faster when treated with PRBM. Thus, the use of this PRBM is an effective option for the treatment of chronic DFUs.

Exploring the Relationship Between Clinical Presentation in Hallux Valgus and Response to AbobotulinumtoxinA Treatment.

The relationship between pain/disability and angular deviation of the hallux valgus (HV), and the impact of orthotic use, laterality, and pain variability on treatment outcomes remain unclear. This was explored in post hoc analyses of a placebo-controlled trial of abobotulinumtoxinA (aboBoNT-A; Dysport®) for HV-associated pain (NCT03569098). The primary endpoint was not met in this study (change from baseline Numeric Pain Rating Scale [NPRS] score vs placebo at week 8); however, there was a greater reduction from baseline in mean NPRS score at week 12 with aboBoNT-A 500U versus placebo (p = .06). Adults with painful HV without surgery were randomized (1:1:1) to aboBoNT-A 300U, aboBoNT-A 500U, or placebo. NPRS was completed for 7 days before baseline and weeks 4, 8, and 12. Over-the-counter orthoses were permitted. Participants (N = 186) had a mean [standard deviation, SD] age of 48.2 [13.1] years, 18% (33/186) used orthotics, and 67% (124/186) had bilateral HV. No associations between baseline pain severity and angular deviation were identified. Participants with high pain variability at baseline (SD > 2) had a poorer response to aboBoNT-A treatment than those with less variability. In conclusion, no relationship between HV-related pain/disability and angular deviation was observed. PLAIN LANGUAGE SUMMARY: A bunion (medical term: hallux valgus) is a common adult foot problem in which the big toe points inward toward the other toes, and this can be painful. How much the big toe points inward (how deformed the foot is) has been linked to the amount of pain the patient experiences. A better understanding of this foot deformity and bunion pain will help doctors and patients to make the right treatment decisions. A study was completed looking at how injections of a type of botulinum toxin (abobotulinumtoxinA) into specific muscles in the foot may help to reduce bunion pain in patients without surgery. This subsequent analysis of the study data looked at the amount of foot deformity in patients, the bunion pain they experienced, and which factors affected how well abobotulinumtoxinA worked to reduce bunion pain. The results of this study showed that the amount of foot deformity was not linked to the level of bunion pain. When deciding the best treatment option to relieve bunion pain, it is important that doctors not only consider how deformed the foot is, but also other important factors such as foot pain levels.

Pain Reduction With AbobotulinumtoxinA for the Treatment of Hallux Valgus in Adult Participants: Results of a Randomized and Placebo-Controlled Phase 2 Trial.

AbobotulinumtoxinA (aboBoNT-A, Dysport® [Ipsen, Paris, France]) inhibits acetylcholine release at the neuromuscular junction and may modulate pain signaling in hallux valgus (HV). This randomized study (NCT03569098) included a double-blind phase (aboBoNT-A 300U, 500U or placebo injections into forefoot muscles) and an open-label aboBoNT-A treatment period in participants with an HV diagnosis and no HV surgery. The primary endpoint was change from baseline in numeric pain rating scale (NPRS) score at week 8. Secondary endpoints included change in NPRS (other time points) and proportion of participants with ≥20% reduction from baseline NPRS (responders). Post-hoc analyses assessed number of days in a 7-day evaluation period that participants spent in a lower pain state than at baseline. Participants received aboBoNT-A 300U (n = 63), 500U (n = 60) or placebo (n = 63). Superiority to placebo was not observed with either aboBoNT-A dose at week 8, thus the primary endpoint was unmet. At week 12, a trend toward efficacy was observed with aboBoNT-A 500U versus placebo and the proportion of participants with ≥20% reduction from baseline NPRS was greater with aboBoNT-A 500U versus placebo (p = .006). Participants in the aboBoNT-A 500U group spent more days with lower NPRS than their lowest baseline score, and with NPRS ≥2 points lower than their mean baseline NPRS at weeks 8 and 12 versus placebo (all p < .05; post-hoc). AboBoNT-A was well tolerated. Although the primary endpoint was unmet, other endpoints showed a nominal advantage for aboBoNT versus placebo for treatment of HV-related pain, particularly at week 12. Further clinical evaluation is needed to establish whether botulinum toxins represent a viable non-operative treatment option for HV-associated pain. PLAIN LANGUAGE SUMMARY: Hallux valgus is the medical name for a bunion, a foot deformity that can worsen over time. Patients with bunions experience pain and walking can become difficult, which can affect their quality of life. Foot support aids (e.g., braces, splints and inserts) are available, but surgery is the standard treatment. This study looked at how injections of a specific type of botulinum toxin, called abobotulinumtoxinA or "aboBoNT-A", into the foot may help to reduce pain in patients with bunions. The study included 186 patients aged 18 to 75 years who had not had surgery on their bunion. The researchers looked at how well the injections worked using scales that measure the pain levels the patient experienced. The main outcome was whether patients who had aboBoNT-A injections had less pain after 8 weeks than they did before treatment. The study included patients who were injected with saltwater (no treatment) to check that any treatment effect was real. Researchers also looked at the results after 12 weeks, as well as how many patients had less pain after treatment than before and how many days in a given week patients experienced less pain after treatment than they did before. There was no reduction in pain levels with aboBoNT-A injections after 8 weeks compared with no treatment. However, the other study outcomes suggested that aboBoNT-A resulted in a small benefit compared with no treatment, especially after 12 weeks. Further medical research is needed to establish whether botulinum toxins represent an alternative treatment to surgery for the pain associated with bunions.

Plate Fixation in Midfoot and Ankle Charcot Neuroarthropathy.

Surgical reconstruction of Charcot arthropathy in the foot and ankle is extremely difficult. The fundamentals of reconstruction are necessary to provide adequate outcome. Removing and resecting the diseased bone is needed along with good anatomic alignment and rigid fixation. This reconstructive surgery is not only difficult from medical management point of view but also involves patient compliance and good technical components of the surgery from the surgeon. The surgeon must have skills with internal and external fixation, a good understanding of lower extremity vascular disease, and a good understanding of infectious disease and plastic surgical techniques of the lower extremity.

Use of a purified reconstituted bilayer matrix in the management of chronic diabetic foot ulcers improves patient outcomes vs standard of care: Results of a prospective randomised controlled multi-centre clinical trial.

Diabetic foot infections continue to be a major challenge for health care delivery systems. Following encouraging results from a pilot study using a novel purified reconstituted bilayer matrix (PRBM) to treat chronic diabetic foot ulcers (DFUs), we designed a prospective, multi-centre randomised trial comparing outcomes of PRBM at 12 weeks compared with a standard of care (SOC) using a collagen alginate dressing. The primary endpoint was percentage of wounds closed after 12 weeks. Secondary outcomes included assessments of complications, healing time, quality of life, and cost to closure. Forty patients were included in an intent-to-treat (ITT) and per-protocol (PP) analysis, with 39 completing the study protocol (n = 19 PRBM, n = 20 SOC). Wounds treated with PRBM were significantly more likely to close than wounds treated with SOC (ITT: 85% vs 30%, P = .0004, PP: 94% vs 30% P = .00008), healed significantly faster (mean 37 days vs 67 days for SOC, P = .002), and achieved a mean wound area reduction within 12 weeks of 96% vs 8.9% for SOC. No adverse events (AEs) directly related to PRBM treatment were reported. Mean PRBM cost of healing was $1731. Use of PRBM was safe and effective for treatment of chronic DFUs.

Improved healing of chronic diabetic foot wounds in a prospective randomised controlled multi-centre clinical trial with a microvascular tissue allograft.

This study assesses the impact of a processed microvascular tissue (PMVT) allograft on wound closure and healing in a prospective, single-blinded, multi-centre, randomised controlled clinical trial of 100 subjects with Wagner Grade 1 and 2 chronic neuropathic diabetic foot ulcerations. In addition to standard wound care, including standardised offloading, the treatment arm received PMVT while the control arm received a collagen alginate dressing. The primary endpoint was complete wound closure at 12 weeks. Secondary endpoints assessed on all subjects were percent wound area reduction, time to healing, and local neuropathy. Novel exploratory sub-studies were conducted for wound area perfusion and changes in regional neuropathy. Weekly application of PMVT resulted in increased complete wound closure at 12 weeks (74% vs 38%; P = .0003), greater percent wound area reduction from weeks four through 12 (76% vs 24%; P = .009), decreased time to healing (54 days vs 64 days; P = .009), and improved local neuropathy (118% vs 11%; P = .028) compared with the control arm. Enhanced perfusion and improved regional neuropathy were demonstrated in the sub-studies. In conclusion, this study demonstrated increased complete healing with PMVT and supports its use in treating non-healing DFUs. The observed benefit of PMVT on the exploratory regional neuropathy and perfusion endpoints warrants further study.

A multi-centre, single-blinded randomised controlled clinical trial evaluating the effect of resorbable glass fibre matrix in the treatment of diabetic foot ulcers.

Diabetic foot ulcers (DFUs) are at risk for detrimental complications even with current, standard of care (SOC) treatments. The primary objective of this randomised controlled trial was to compare a unique resorbable glass microfiber matrix (Mirragen; Advanced Wound Matrix [BBGFM]; ETS Wound Care, Rolla, Missouri) compared with a standard of care group (SOC, collagen alginate dressing) at 12 weeks. Both groups received standard diabetic foot care including glucose monitoring, weekly debridements when needed and an offloading device. The primary endpoint was proportion of full-thickness, non-infected, non-ischaemic wounds healed at 12 weeks, with secondary endpoints including percent area reduction (PAR) and changes in Semmes-Weinstein monofilament testing. The result illustrated in the intent-to-treat analysis at 12 weeks showed that 70% (14/20) of the BBGFM-treated DFUs healed compared with 25% (5/20) treated with SOC alone (adjusted P = .006). Mean PAR at 12 weeks was 79% in the BBGFM group compared with 37% in the SOC group (adjusted P = .027). Mean change in neuropathic score between baseline and up to 12 weeks of treatment was 2.0 in the BBGFM group compared with -0.6 in the SOC group where positive improvement in scores are better (adjusted P = .008). The mean number of BBGFM applications was 6.0. In conclusion, adding BBGFM to SOC significantly improved wound healing with no adverse events related to treatment compared with SOC alone.

Hallux and Lesser Digits Deformities Associated with Cavus Foot.

It is important to identify the level of the deformity or deformities. It is important to get the limb as close to anatomic alignment as possible. Many levels and multiple procedures may be involved with this reconstruction.

The Cavovarus Ankle: Approaches to Ankle Instability and Inframalleolar Deformity.

Pathologic affects from a cavus foot deformity range from flexible subtle to rigid severe deformities and are related to many pathologic conditions of the foot and ankle. Understanding the underlying deformity and the deforming force is essential in treating the cavus ankle and foot. Every deformity is different and unique to a given patient; therefore, surgical plans should be modified to each patient.

Woringer-Kolopp Disease of the Foot: A Case Report.

Woringer-Kolopp disease is a rare variant of mycosis fungoides, a type of cutaneous T-cell lymphoma. Described is a case of a small annular plaque on the foot diagnosed histologically as Woringer-Kolopp disease and treated successfully with topical and intralesional steroids. In addition, a brief review of the literature and treatment options is provided.

Placental Membrane Provides Improved Healing Efficacy and Lower Cost Versus a Tissue-Engineered Human Skin in the Treatment of Diabetic Foot Ulcerations.

Aseptically processed dehydrated human amnion and chorion allograft (dHACA) (AmnioBand) has shown great promise in the treatment of recalcitrant diabetic foot ulcers (DFUs) when compared with standard wound care but has not yet been compared to any other tissue forms used in treating DFUs. The hypothesis was to conduct a randomized controlled trial in which dHACA was compared to one of the earliest and most commonly accepted tissue-engineered skin substitutes (TESS) (Apligraf) in the treatment of nonhealing DFUs over a period of 12 weeks to assess the superiority of healing. METHODS: Following a 2-week screening period during which subjects with DFUs were treated with collagen alginate dressing, 60 subjects were randomized at 5 sites to receive either dHACA or TESS applied weekly, with weekly follow-up for up to 12 weeks. RESULTS: The mean time to heal within 6-week time period for the dHACA group was 24 days (95% CI, 18.9-29.2) versus 39 days (95% CI, 36.4-41.9) for the TESS group; the mean time to heal at 12 weeks was 32 days (95% CI, 22.3-41.0) for dHACA-treated wounds versus 63 days (95% CI, 54.1-72.6) for TESS-treated wounds. The proportion of wounds healed at study completion (12 weeks) was 90% (27/30) for the dHACA group versus 40% (12/30) for the TESS group. The mean product cost for the dHACA group was significantly lower than that for the TESS group [dHACA: $2,200 (median: $1,300); TESS: $7,900 (median: $6,500)]. The mean wastage (%) at 12 weeks was also significantly lower for the dHACA group than that for the TESS group (36% vs 95%). CONCLUSIONS: It was concluded that aseptically processed dHACA heals diabetic foot wounds more reliably, statistically significantly faster than and at significantly lower cost than TESS.

Calcaneal Bone Graft Procedures: An Analysis of Postsurgical Complications.

The purpose of this article is to examine complications in patients who underwent bone grafting from the calcaneus between December 2001 and June 2010. This retrospective, single-practice study included 247 procedures in 242 patients, including 200 (82.64%) female and 42 (17.36%) male patients, ranging in age from 13 to 89 (median 49) years. Overall, the incidence of experiencing any form of complication was 2.43% (6 of 247); these included 5 (2.02%) feet that displayed donor site sural neuritis and 1 (0.41) that displayed a painful, hypertrophic scar at the donor site. The only statistically significant risk factor associated with the development of a calcaneal donor site complication was white race (being African American was protective). These findings indicate that procurement of autogenous bone graft from the calcaneus, as described in this report, is safe and dependable with a low incidence of complications, and irritation of the sural nerve is the most common complication associated with the procedure. Further clinical and long-term follow-up studies controlling for confounding variables need to be performed to fully determine the overall safety and efficacy of this procedure.

Use of an aseptically processed, dehydrated human amnion and chorion membrane improves likelihood and rate of healing in chronic diabetic foot ulcers: A prospective, randomised, multi-centre clinical trial in 80 patients.

Amnion and chorion allografts have shown great promise in healing diabetic foot ulcers (DFUs). Results from an interim analysis of 40 patients have demonstrated the accelerated healing ability of a novel aseptically processed, dehydrated human amnion and chorion allograft (dHACA). The goal of this study was to report on the full trial results of 80 patients where dHACA was compared with standard of care (SOC) in achieving wound closure in non-healing DFUs. After a 2-week screening period, during which patients with DFUs were unsuccessfully treated with SOC, patients were randomised to either SOC alone or SOC with dHACA applied weekly for up to 12 weeks. At 12 weeks, 85% (34/40) of the dHACA-treated DFUs healed, compared with 33% (13/40) treated with SOC alone. Mean time to heal within 12 weeks was significantly faster for the dHACA- treated group compared with SOC, 37 days vs 67 days in the SOC group (P = .000006). Mean number of grafts used per healed wound during the same time period was 4.0, and mean cost of the tissue to heal a DFU was $1771. The authors concluded that aseptically processed dHACA heals DFUs significantly faster than SOC at 12 weeks.

An aseptically processed, acellular, reticular, allogenic human dermis improves healing in diabetic foot ulcers: A prospective, randomised, controlled, multicentre follow-up trial.

Aseptically processed human reticular acellular dermal matrix (HR-ADM) has been previously shown to improve wound closure in 40 diabetic patients with non-healing foot ulcers. The study was extended to 40 additional patients (80 in total) to validate and extend the original findings. The entire cohort of 80 patients underwent appropriate offloading and standard of care (SOC) during a 2-week screening period and, after meeting eligibility criteria, were randomised to receive weekly applications of HR-ADM plus SOC or SOC alone for up to 12 weeks. The primary outcome was the proportion of wounds closed at 6 weeks. Sixty-eight percent (27/40) in the HR-ADM group were completely healed at 6 weeks compared with 15% (6/40) in the SOC group. The proportions of wounds healed at 12 weeks were 80% (34/40) and 30% (12/40), respectively. The mean time to heal within 12 weeks was 38 days for the HR-ADM group and 72 days for the SOC group. There was no incidence of increased adverse or serious adverse events between groups or any graft-related adverse events. The mean and median HR-ADM product costs at 12 weeks were $1200 and $680, respectively. HR-ADM is clinically superior to SOC, is cost effective relative to other comparable treatment modalities, and is an efficacious treatment for chronic non-healing diabetic foot ulcers.

Subtalar Joint Arthrodesis for Elective and Posttraumatic Foot and Ankle Deformities.

Subtalar joint arthrodesis is a procedure used in posttraumatic arthritis, osteoarthritis, tarsal coalition management, posterior tibial tendon dysfunction, and inflammatory arthropathies, and can be used in deformity correction. The goals of the procedure are to eliminate pain, improve function, restore stability, and realign the hind foot. The procedure has high patient satisfaction with low complications while preserving motion in adjacent tarsal joints. Joint preparation is important and time should be spent preparing the joint for successful arthrodesis and the fixation construct needs to be done well and effectively to provide a solid Arbeitsgemeinschaft für Osteosynthesefragen (AO) construct for good results.

Human Reticular Acellular Dermal Matrix in the Healing of Chronic Diabetic Foot Ulcerations that Failed Standard Conservative Treatment: A Retrospective Crossover Study.

BACKGROUND: Acellular matrices have been successfully used to heal indolent diabetic foot ulcers (DFUs). These tissues include allogenic dermis as well as xenograft dermis, pericardium, and small intestine submucosa. While all of these tissues show promise for healing DFUs, dermal-derived matrices have shown considerable potential. MATERIALS AND METHODS: The authors retrospectively reviewed healing in patients with DFUs that failed the standard of care (SOC) treatment from a previous prospective randomized, controlled trial (RCT). That trial compared the efficacy of human reticular acellular dermal matrices (HR-ADMs) with the SOC. Of the 16 out of 20 patients who did not heal in the SOC group, 12 were eligible for crossover treatment with the HR-ADM. The authors studied the rate of complete healing in that specific cohort after 12 weeks of crossover treatment. RESULTS: Of the 12 patients who were eligible for the HR-ADM, 10 (83%) achieved complete wound healing, with a mean healing time of 21 days to closure. The corresponding wound area reduction was from 1.7 cm2 to 0.6 cm2. The mean product cost to closure was $800/patient. CONCLUSION: This study further demonstrates the effectiveness of the HR-ADM in facilitating the closure of nonhealing DFUs refractory to SOC.

A prospective, randomised, controlled, multicentre clinical trial examining healing rates, safety and cost to closure of an acellular reticular allogenic human dermis versus standard of care in the treatment of chronic diabetic foot ulcers.

Acellular dermal matrices can successfully heal wounds. This study's goal was to compare clinical outcomes of a novel, open-structure human reticular acellular dermis matrix (HR-ADM) to facilitate wound closure in non-healing diabetic foot ulcers (DFUs) versus DFUs treated with standard of care (SOC). Following a 2-week screening period in which DFUs were treated with offloading and moist wound care, patients were randomised to either SOC alone or HR-ADM plus SOC applied weekly for up to 12 weeks. At 6 weeks, the primary outcome time, 65% of the HR-ADM-treated DFUs healed (13/20) compared with 5% (1/20) of DFUs that received SOC alone. At 12 weeks, the proportions of DFUs healed were 80% and 20%, respectively. Mean time to heal within 12 weeks was 40 days for the HR-ADM group compared with 77 days for the SOC group. There was no incidence of increased adverse or serious adverse events between groups or any adverse events related to the graft. Mean and median graft costs to closure per healed wound in the HR-ADM group were $1475 and $963, respectively. Weekly application of HR-ADM is an effective intervention for promoting closure of non-healing DFUs.

Aseptically Processed Placental Membrane Improves Healing of Diabetic Foot Ulcerations: Prospective, Randomized Clinical Trial.

BACKGROUND: Allogeneic grafts derived from amnion/chorion are known to be efficacious in healing chronic diabetic foot ulcerations (DFUs). The goal of this study was to compare aseptically processed dehydrated human amnion and chorion allograft (dHACA) versus standard of care (SOC) in facilitating wound closure in nonhealing DFUs. METHODS: Patients with DFUs treated with SOC (off-loading, appropriate debridement, and moist wound care) after a 2-week screening period were randomized to either SOC or wound-size-specific dHACA (AmnioBand, Musculoskeletal Transplant Foundation, Edison, N.J.) applied weekly for up to 12 weeks plus SOC. Primary endpoint was the percentage of wounds healed at 6 weeks between groups. RESULTS: At 6 weeks, 70% (14/20) of the dHACA-treated DFUs healed compared with 15% (3/20) treated with SOC alone. Furthermore, at 12 weeks, 85% (17/20) of the DFUs in the dHACA group healed compared with 25% (5/20) in the SOC group, with a corresponding mean time to heal of 36 and 70 days, respectively. At 12 weeks, the mean number of grafts used per healed wound for the dHACA group was 3.8 (median 3.0), and mean cost of the tissue to heal a DFU was $1400. The mean wastage at 12 weeks was 40%. One adverse event and 1 serious adverse event occurred in the dHACA group; neither was graft related. Three adverse events and 1 serious adverse event occurred in the SOC group. CONCLUSION: Aseptically processed dHACA heals diabetic foot wounds significantly faster than SOC at 6 and 12 weeks with minimal graft wastage.

A Multicenter, Retrospective Study of Early Weightbearing for Modified Lapidus Arthrodesis.

The modified Lapidus arthrodesis is a long-established surgical technique for management of hallux valgus that provides reproducible results and quality patient outcomes. The data from 367 consecutive patients undergoing unilateral modified Lapidus arthrodesis from January 1, 2007 to December 31, 2008 at participating centers were retrospectively evaluated. The included patients were categorized into early weightbearing (≤ 21 days) and delayed weightbearing (> 21 days) groups. A total of 24 nonunions (6.5%) were identified, with 13 (7.1%) in the early weightbearing group and 11 (6.0%) in the delayed weightbearing group. To date, the present study is the largest multicenter investigation to evaluate early weightbearing after modified Lapidus arthrodesis and the only large study to directly compare early and delayed weightbearing. The findings of the present study have shown that early weightbearing for modified Lapidus arthrodesis does not increase the risk of nonunion when evaluating various fixation constructs.