A Multi-Faceted Digital Health Solution for Monitoring and Managing Diabetic Foot Ulcer Risk: A Case Series.

INTRODUCTION: Diabetic foot ulcers (DFU) are a devastating complication of diabetes. There are numerous challenges with preventing diabetic foot complications and barriers to achieving the care processes suggested in established foot care guidelines. Multi-faceted digital health solutions, which combine multimodal sensing, patient-facing biofeedback, and remote patient monitoring (RPM), show promise in improving our ability to understand, prevent, and manage DFUs. METHODS: Patients with a history of diabetic plantar foot ulcers were enrolled in a prospective cohort study and equipped with custom sensory insoles to track plantar pressure, plantar temperature, step count, and adherence data. Sensory insole data enabled patient-facing biofeedback to cue active plantar offloading in response to sustained high plantar pressures, and RPM assessments in response to data trends of concern in plantar pressure, plantar temperature, or sensory insole adherence. Three non-consecutive case participants that ultimately presented with pre-ulcerative lesions (a callus and/or erythematous area on the plantar surface of the foot) during the study were selected for this case series. RESULTS: Across three illustrative patients, continuous plantar pressure monitoring demonstrated promise for empowering both the patient and provider with information for data-driven management of pressure offloading treatments. CONCLUSION: Multi-faceted digital health solutions can naturally enable and reinforce the integrative foot care guidelines. Multi-modal sensing across multiple physiologic domains supports the monitoring of foot health at various stages along the DFU pathogenesis pathway. Furthermore, digital health solutions equipped with remote patient monitoring unlock new opportunities for personalizing treatments, providing periodic self-care reinforcement, and encouraging patient engagement-key tools for improving patient adherence to their diabetic foot care plan.

Preventative Sensor-Based Remote Monitoring of the Diabetic Foot in Clinical Practice.

Diabetes and its complications, particularly diabetic foot ulcers (DFUs), pose significant challenges to healthcare systems worldwide. DFUs result in severe consequences such as amputation, increased mortality rates, reduced mobility, and substantial healthcare costs. The majority of DFUs are preventable and treatable through early detection. Sensor-based remote patient monitoring (RPM) has been proposed as a possible solution to overcome limitations, and enhance the effectiveness, of existing foot care best practices. However, there are limited frameworks available on how to approach and act on data collected through sensor-based RPM in DFU prevention. This perspective article offers insights from deploying sensor-based RPM through digital DFU prevention regimens. We summarize the data domains and technical architecture that characterize existing commercially available solutions. We then highlight key elements for effective RPM integration based on these new data domains, including appropriate patient selection and the need for detailed clinical assessments to contextualize sensor data. Guidance on establishing escalation pathways for remotely monitored at-risk patients and the importance of predictive system management is provided. DFU prevention RPM should be integrated into a comprehensive disease management strategy to mitigate foot health concerns, reduce activity-associated risks, and thereby seek to be synergistic with other components of diabetes disease management. This integrated approach has the potential to enhance disease management in diabetes, positively impacting foot health and the healthspan of patients living with diabetes.

Efficacy of a polylactic acid matrix for the closure of Wagner grade 1 and 2 diabetic foot ulcers: a single-center, prospective randomized trial.

INTRODUCTION: CAMPs are used for treating refractory DFUs where other treatments have failed. PLA is a CAMP that has demonstrated effectiveness in promoting healing in burns and acute wounds. OBJECTIVE: A single-center, prospective, randomized controlled trial comparing PLA-guided closure matrices versus collagen dressings was conducted to assess healing of Wagner grades 1 and 2 DFUs. MATERIALS AND METHODS: A total of 30 participants were randomized to receive weekly debridement, wound care, and DFU offloading plus either PLA or collagen CAMPs. The primary outcome was the time to achieve full healing, and the secondary outcome was the proportion of ulcers healed at 12 weeks. RESULTS: The median time to achieve full healing was 9.3 ± 2.9 weeks in the PLA group versus 14.8 ± 8.1 weeks in the collagen group (P = .021), representing a 44% reduction in the time to heal. Furthermore, by 12 weeks, 80% of the PLA-treated ulcers were healed compared to only 33% in the collagen group (P = .025). CONCLUSION: The results of this study show PLA matrices induce a potent healing response that leads to reduced healing time and an increased OR for achieving healing by 12 weeks.

Final efficacy and cost analysis of a fish skin graft vs standard of care in the management of chronic diabetic foot ulcers: a prospective, multicenter, randomized controlled clinical trial.

INTRODUCTION: DFUs remain a cause of significant morbidity. OBJECTIVE: This is the third of 3 planned articles reporting on a prospective, multicenter, randomized controlled trial evaluating the use of omega-3-rich acellular FSG compared with CAT in the management of DFUs. MATERIALS AND METHODS: A total of 102 patients with a DFU (n = 51 FSG, n = 51 CAT) participated in the trial as ITT candidates, with 77 of those patients included in the PP analysis (n = 43 FSG, n = 34 CAT). Six months after treatment, patients with healed ulcers were followed up for ulcer recurrence. A cost analysis model was applied in both treatment groups. RESULTS: The proportion of closed wounds at 12 weeks was compared, as were the secondary outcomes of healing rate and mean PAR. Diabetic foot wounds treated with FSG were significantly more likely to achieve closure than those managed with CAT (ITT: 56.9% vs 31.4%; P =.0163). The mean PAR at 12 weeks was 86.3% for FSG vs 64.0% for CAT (P =.0282). CONCLUSIONS: Treatment of DFUs with FSG resulted in significantly more wounds healed and an annualized cost savings of $2818 compared with CAT.

Preliminary Clinical Evaluation Using a Novel Bioengineered Wound Product to Treat Lower Extremity Ulcers.

Diabetes mellitus affects hundreds of millions of people worldwide, each of which have up to a 25% risk of developing a diabetic foot ulcer (DFU) during their lifetime. With poor DFU healing rates using standard of care, advanced treatments are introduced to attempt to close the wound. The objective of this preliminary clinical evaluation was to evaluate lower extremity ulcers treated with a novel bioengineered wound product (BWP). The BWP, a solid absorbable and conformable sheet composed of gelatin, Manuka honey, and hydroxyapatite, was applied on 12 patients with lower extremity ulcers. The patients in this evaluation spanned across 4 sites and had complicated medical histories, including little to no progression of healing with standard of care or treatment with other biomaterials. The ulcers were treated with debridement, BWP placement, dressing, appropriate compression, and offloading as necessary. Weekly follow-up visits were recommended for evaluation, debridement, and BWP reapplication. Nine patients had the BWP applied to aid in full closure. These patients achieved 100% closure within 8 weeks, with a mean closure time of 4.1 weeks. At 4 weeks, the mean percent wound closure was 94%. Three patients had the BWP applied to aid in achieving a healthy wound bed for continued treatment (eg, splitthickness skin graft) and to cover (epithelialization over) an exposed tendon. In all 12 cases, no treatment site infections were observed. The results and observations from this preliminary clinical evaluation suggest that the BWP supports rapid wound closure, a predictor of complete healing for DFUs.

Evaluating the effect of omega-3-rich fish skin in the treatment of chronic, nonresponsive diabetic foot ulcers: penultimate analysis of a multicenter, prospective, randomized controlled trial.

OBJECTIVE: This is the second of 3 planned articles reporting on a prospective, multicenter, randomized controlled trial assessing the efficacy of fish skin graft in the management of diabetic foot ulcers in comparison with the standard of care (collagen alginate dressing). MATERIALS AND METHODS: The primary end point of this prospective randomized trial is the number of closed wounds at 12 weeks. RESULTS: As of the time of this writing, 94 patients had completed the protocol. At 12-week follow-up, healing was achieved in 63.0% of index ulcers (29 of 46 patients) in the acellular fish skin graft group compared with 31.3% in the control group (15 of 48 patients) (P =.0036). In both groups, the mean time to healing was 7 weeks. The median number of applications of the fish skin graft to achieve healing was 6. CONCLUSION: A clinically and statistically significant difference in healing was observed between patients treated with acellular fish skin graft and those treated with a collagen alginate dressing. The data support the completion of this prospective randomized trial.

A Multicenter, Blinded, Randomized Controlled Clinical Trial Evaluating the Effect of Omega-3-Rich Fish Skin in the Treatment of Chronic, Nonresponsive Diabetic Foot Ulcers.

INTRODUCTION: Omega-3-rich fish skin grafts have been shown to accelerate wound healing in full-thickness wounds. OBJECTIVE: The goal of this study was to compare the fish skin graft with standard of care (SOC) using collagen alginate dressing in the management of treatment-resistant diabetic foot ulcers (DFUs), defined as superficial ulcers not involving tendon capsule or bone. MATERIALS AND METHODS: Patients with DFUs who were first treated with SOC (offloading, appropriate debridement, and moist wound care) for a 2-week screening period were then randomized to either receiving SOC alone or SOC plus fish skin graft applied weekly for up to 12 weeks. The primary endpoint was the percentage of wounds closed at 12 weeks. RESULTS: Forty-nine patients were included in the final analysis. At 12 weeks, 16 of 24 patients' DFUs (67%) in the fish skin arm were completely closed, compared with 8 of 25 patients' DFUs (32%) in the SOC arm (P value = .0152 [N = 49]; significant at P < .047). At 6 weeks, the percentage area reduction was 41.2% in the SOC arm and 72.8% in the fish skin arm. CONCLUSIONS: The application of fish skin graft to previously nonresponsive DFUs resulted in significantly more fully healed wounds at 12 weeks than SOC alone. The study findings support the use of fish skin graft for chronic DFUs that do not heal with comprehensive SOC treatment.

Proactive and Early Aggressive Wound Management: A Shift in Strategy Developed by a Consensus Panel Examining the Current Science, Prevention, and Management of Acute and Chronic Wounds.

Normal wound healing is accomplished through a series of well-coordinated, progressive events with overlapping phases. Chronic wounds are described as not progressing to healing or not being responsive to management in a timely manner. A consensus panel of multidisciplinary wound care professionals was assembled to (1) educate wound care practitioners by identifying key principles of the basic science of chronic wound pathophysiology, highlighting the impact of metalloproteinases and biofilms, as well as the role of the extracellular matrix; and (2) equip practitioners with a systematic strategy for the prevention and healing of acute injuries and chronic wounds based upon scientific evidence and the panel members' expertise. An algorithm is presented that represents a shift in strategy to proactive and early aggressive wound management. With proactive management, adjunct therapies are applied preemptively to acute injuries to reduce wound duration and risk of chronicity. For existing chronic wounds, early aggressive wound management is employed to break the pathophysiology cycle and drive wounds toward healing. Reducing bioburden through debridement and bioburden management and using collagen dressings to balance protease activity prior to the use of advanced modalities may enhance their effectiveness. This early aggressive wound management strategy is recommended for patients at high risk for chronic wound development at a minimum. In their own practices, the panel members apply this systematic strategy for all patients presenting with acute injuries or chronic wounds.

Total Contact Cast System to Heal Diabetic Foot Ulcers.

Off-loadinga diabetic foot ulcer is a cornerstone of quality wound care for diabetic patients to allow cellular growth in the wound bed. While total contact casts (TCC) have been described as the gold standard for off-loading the wound, the complexity of application and the time commitment for both application and drying have discouraged health professionals from using them. This retrospective case series, conducted in a podiatric practice, evaluated using a TCC system that helps address the three components in which guidelines should be addressed when caring for a diabetic foot: V - vascular management, I - infection management and prevention, and P - pressure relief. This studied TCC system can be applied in approximately seven minutes and the patient can ambulate immediately without waiting for drying. Of the 20 wounds treated with this TCC, 18/20 (90%) healed in a mean of 22.3 days. The mean number of TCC treatments was 2.8. When compared to evidence published in the scientific literature documenting healing outcomes using various TCCs, this system has the fastest observational healing rate. In this case series, this TCC system for off-loading was found to be clinically beneficial for the patient in a physician's office practice.

Ovine-Based Collagen Matrix Dressing: Next-Generation Collagen Dressing for Wound Care.

Significance: Broad-spectrum metalloproteinase (MMP) reduction along with inherent aspects of an extracellular matrix (ECM) dressing can bring about improved wound healing outcomes and shorter treatment duration. Initial reports of clinical effectiveness of a new ovine-based collagen extracellular matrix (CECM) dressing demonstrate benefits in chronic wound healing. Recent Advances: CECM dressings are processed differently than oxidized regenerated cellulose/collagen dressings. CECM dressings consist primarily of collagens I and III arranged as native fibers that retain the three-dimensional architecture present in tissue ECM. As such, ovine-based ECM dressings represent a new generation of collagen dressings capable of impacting a broad spectrum of MMP excess known to be present in chronic wounds. Critical Issues: While MMPs are essential in normal healing, elevated presence of MMPs has been linked to wound failure. Collagen has been shown to reduce levels of MMPs, acting as a sacrificial substrate for excessive proteases in a chronic wound. Preserving collagen dressings in a more native state enhances bioactivity in terms of the ability to affect the chronic wound environment. Clinical observation and assessment may not be sufficient to identify a wound with elevated protease activity that can break down ECM, affect wound fibroblasts, and impair growth factor response. Future Directions: Collagen dressings that target broad-spectrum excessive MMP levels and can be applied early in the course of care may positively impact healing rates in difficult wounds. Next-generation collagen dressings offer broader MMP reduction capacity while providing a provisional dermal matrix or ECM.

Gentian Violet and Methylene Blue Polyvinyl Alcohol Foam Antibacterial Dressing as a Viable Form of Autolytic Debridement in the Wound Bed.

The objective of this article is to describe the results of a comparative porcine study that evaluated the effectiveness of a gentian violet and methylene blue (GV/MB) polyvinyl alcohol (PVA) antibacterial foam dressing in debriding eschar. The authors performed an in vivo, preclinical study on eschar-covered porcine wounds. Two clinical case studies are also included. Test products, GV/MB antibacterial foam dressing, collagenase ointment, collagenase ointment plus GV/MB antibacterial foam dressing, medical-grade honey, and moist gauze dressing (control), were applied to porcine wounds using a split-back study design. The percent of eschar removal and wound closure were measured and recorded at time points up to 14 days. Statistically significant reduction in eschar was observed with GV/MB dressing and with GV/MB dressing with collagenase. By day 14, the wounds with GV/MB dressing alone and GV/MB dressing with collagenase had eschar covering less than 25% of the wound bed area compared with collagenase alone, medical grade honey, or moist gauze control, which showed eschar still covering over 75% of the wound bed area. Autolytic debridement activity of GV/MB foam dressings was evident in the porcine eschar study, as well as in the cases described.

The use of PriMatrix, a fetal bovine acellular dermal matrix, in healing chronic diabetic foot ulcers: a prospective multicenter study.

OBJECTIVE: The objective of this multicenter study was to prospectively evaluate the healing outcomes of chronic diabetic foot ulcers (DFUs) treated with PriMatrix (TEI Biosciences, Boston, Massachusetts), a fetal bovine acellular dermal matrix. METHODS: Inclusion criteria required the subjects to have a chronic DFU that ranged in area from 1 to 20 cm² and failed to heal more than 30% during a 2-week screening period when treated with moist wound therapy. For qualifying subjects, PriMatrix was secured into a clean, sharply debrided wound; dressings were applied to maintain a moist wound environment, and the DFU was pressure off-loaded. Wound area measurements were taken weekly for up to 12 weeks, and PriMatrix was reapplied at the discretion of the treating physician. RESULTS: A total of 55 subjects were enrolled at 9 US centers with 46 subjects progressing to study completion. Ulcers had been in existence for an average of 286 days, and initial mean ulcer area was 4.34 cm². Of the subjects completing the study, 76% healed by 12 weeks with a mean time to healing of 53.1 ± 21.9 days. The mean number of applications for these healed wounds was 2.0 ± 1.4, with 59.1% healing with a single application of PriMatrix and 22.9% healing with 2 applications. For subjects not healed by 12 weeks, the average wound area reduction was 71.4%. CONCLUSION: The results of this multicenter prospective study demonstrate that the use of PriMatrix integrated with standard-of-care therapy is a successful treatment regimen to heal DFUs.

Clinical outcomes following the use of ovine forestomach matrix (endoform dermal template) to treat chronic wounds.

The suitability of the ovine forestomach matrix (OFM) for the treatment of recalcitrant wounds was evaluated in 19 patients. At 12 weeks, 50% of wounds had closed, and the average reduction in surface area was 73.4%. Promising outcomes of this initial series support the clinical consideration of OFM.

A retrospective analysis of 22 patients treated with percutaneous radiofrequency nerve ablation for prolonged moderate to severe heel pain associated with plantar fasciitis.

UNLABELLED: A retrospective study involving 22 patients (31 feet) with a history of prolonged moderate to severe heel pain associated with plantar fasciitis were examined to determine if ablation of the sensory branch of the medial calcaneal nerve would result in symptomatic relief. Participants in this study were given subjective questionnaires and visual analog scales in order to rate their symptoms before and after nerve ablation using radiofrequency energy. The results showed that the mean preintervention visual analog pain score was 8.12 +/- 1.61 (with 10 being the worst pain the patient could imagine), and this dropped to 3.26 +/- 1.97 after 1 week and 1.46 +/- 1.76 after 1 month, 1.96 +/- 1.98 at 3 months, and 2.07 +/- 2.06 at 6 months, and the improvement was statistically significant (P < .001) at each stage of follow-up. Furthermore, patients followed for up to 1 year showed no significant worsening of symptoms. Adverse events were limited to hematoma at the site of entry of the radiofrequency cannula. These findings support the conclusion that radiofrequency nerve ablation be considered an alternative to repetitive corticosteroid injections or open surgical intervention for the treatment of recalcitrant plantar heel pain. LEVEL OF CLINICAL EVIDENCE: 4.

Histologic evaluation of a 6-month GraftJacket matrix biopsy used for Achilles tendon augmentation.

BACKGROUND: Assessing implanted biological reinforcement graft success in soft-tissue repairs is typically limited to noninvasive measurements and functional outcome measures. However, there are times when a histologic snapshot of the graft incorporation may be possible owing to a nongraft-related postoperative complication, such as hardware failure. METHODS: We histologically evaluated a 6-month biopsy sample from an Achilles tendon repair augmented with an acellular human dermal matrix (AHDM). A 57-year-old woman was treated for Haglund's deformity of the Achilles tendon. The Achilles tendon was fixed to the calcaneus using a plate, and an AHDM was used to augment the primary repair of the tendon. At 6 months, the hardware was removed owing to prominence, and a biopsy of the AHDM was performed. The specimen was prepared and stained using hematoxylin and eosin, Verhoeff-van Gieson, Movat's pentachrome, and toluidine blue stains. RESULTS: Visually, the graft appeared normal and incorporated with the native tendon. No repeated tear was observed, and results of tests for infection were negative. Histologically, the graft was infiltrated predominantly with fibroblasts and demonstrated numerous blood vessels. Positive proteoglycan staining in the AHDM and at sites of vascularity indicated probable transformation to tendon-like tissue. CONCLUSIONS: These histologic findings suggest that the AHDM is highly biocompatible, supports revascularization and repopulation with noninflammatory host cells, and becomes incorporated by surrounding tendon tissue.

A multicenter study involving the use of a human acellular dermal regenerative tissue matrix for the treatment of diabetic lower extremity wounds.

This multicenter, retrospective study presents the use of a human acellular dermal regenerative tissue matrix as an alternative treatment for 100 chronic, full-thickness wounds of the lower extremity in 75 diabetic patients. Comorbidities included cardiac disease (86.0%), neuropathy (86.0%), peripheral vascular disease (82.0%), infection (54.0%), obesity (51.0%), and osteomyelitis (37.0%). Wound locations included the foot (86.0%), ankle (8.0%), and lower extremity (6.0%). Mean wound age was 20.4 weeks (1.3-191.4 weeks). University of Texas (UT) wound classifications included 15 (15.0%) 1A, 1 (1.0%) 1B, 1 (1.0%) 1C, 2 (2.0%) 1D, 18 (18.0%) 2A, 8 (8.0%) 2B, 5 (5.0%) 2C, 3 (3.0%) 2D, 3 (3.0%) 3A, 7 (7.0%) 3B, 3 (3.0%) 3C, and 34 (34.0%) 3D. The mean time to matrix incorporation, 100% granulation, and complete healing was 1.5 weeks (0.43-4.4 weeks), 5.1 weeks (0.43-16.7 weeks), and 13.8 weeks (1.7-57.8 weeks), respectively. The overall matrix success rate, as defined by full epithelialization, was 90.0%. One failed wound subsequently healed approximately 7 weeks after matrix reapplication. The healing rate was 91.0%, as 91 of the 100 wounds healed. No statistically significant differences were observed between UT classifications and time to matrix incorporation, 100% granulation, and complete healing. Absence of matrix-related complications and high rates of closure in a wide array of diabetic wounds suggest that this matrix is a viable treatment for complex lower extremity wounds. Lack of any statistically significant differences between UT grades and wound outcome end points lends further support to the universal applicability of this matrix, with successful results in both superficial diabetic wounds and in wounds penetrating to the bone or joint.