Grants and Funding in Podiatric Science.

Evidence-based research is essential to improving podiatric medicine and surgery; however, there are many barriers to conducting research, with a major limitation being lack of research funding. There are various grants and funding sources available to podiatric surgeon scientists, but navigating through the resources can be daunting. In this article, we provide a framework for grant writing and funding opportunities for podiatric surgeons to consider.

One-year safety, healing and amputation rates of Wagner 3-4 diabetic foot ulcers treated with cryopreserved umbilical cord (TTAX01).

An open label, multicenter 16-week trial of cryopreserved human umbilical cord (TTAX01) was previously undertaken in 32 subjects presenting with a Wagner grade 3 or 4 diabetic foot ulcer, with 16 (50%) of these having confirmed closure following a median of one product application (previous study). All but two subjects (30/32; 94%) consented to participate in this follow-up study to 1-year postexposure. No restrictions were placed on treatments for open wounds. At 8-week intervals, subjects were evaluated for adverse events (AEs) and wound status (open or closed). Average time from initial exposure to end of follow-up was 378 days (range 343-433), with 29 of 30 (97%) subjects completing a full year. AEs were all typical for the population under study, and none were attributed to prior exposure to TTAX01. One previously healed wound re-opened, one previously unconfirmed closed wound remained healed, and nine new wound closures occurred, giving 25 of 29 (86.2%) healed in the ITT population. Three of the new closures followed the use of various tissue-based products. Three subjects whose wounds were healed required subsequent minor amputations due to osteomyelitis, one of which progressed to a major amputation (1/29; 3.4%). One additional subject underwent two minor amputations prior to healing. Overall, the study found TTAX01 to be safe in long-term follow-up and associated with both a low rate of major amputation and a higher than expected rates of healing.

Infection Protocols for Implants.

Infection can be a devastating complication of surgically inserted prosthetic implants and intramedullary rods, plates and pins. About 2 million implants were inserted in the United States in 2004, and, despite appropriate perioperative antibiotics, approximately 5% of internal fixation devices became infected. Infection rates in fractures that pierce the skin can be as high as 22.7%. Complications of infection include excessive antibiotic use, implant removal, reoperation, and potential amputation. Infections caused by colonized prosthetic implants are often difficult to predict, diagnose, and treat, because they form biofilms. This article explores the approach to infected implants.

An open-label trial of cryopreserved human umbilical cord in the treatment of complex diabetic foot ulcers complicated by osteomyelitis.

Clinical trials of potential new therapies for diabetic foot ulcers rarely enroll patients whose wounds extend to muscle, fascia, or bone with clinical and radiographic evidence of underlying osteomyelitis. An open-label, multicenter trial of cryopreserved human umbilical cord (TTAX01) was undertaken in 32 subjects presenting with such complex wounds with a mean duration of 6.1 ± 9.0 (range: 0.2-47.1) months and wound area at screening of 3.8 ± 2.9 (range: 1.0-9.6) cm2 . Aggressive surgical debridement at baseline resulted in 17 minor amputations and an increase in mean wound area to 7.4 ± 5.8 (range: 1.1-28.6) cm2 . All subjects were placed on systemic antibiotics for at least 6 weeks in conjunction with baseline application of TTAX01. Repeat applications were made at no less than 4-week intervals over the 16-week trial. Initial closure occurred in 18 of 32 (56%) wounds, with 16 (50%) of these having confirmed closure in 16 weeks with a median of one-product application. Cases with biopsy confirmed osteomyelitis (n = 20) showed initial closure in 12 (60%) wounds and confirmed closure in 10 (50%) wounds. Four of the five ulcers presenting as recurrences experienced confirmed closure. Mean overall time to healing was 12.8 ± 4.3 weeks. Mean wound area reduction from baseline was 91% for all wounds. Of the 16 wounds without confirmed closure during the 16-week treatment period, five (31.3%) achieved 99-100% wound area reduction by their final visit. The product was well tolerated. Two minor amputations occurred during the study period due to recurrent or persistent osteomyelitis; however, there were no major amputations.

Interprofessionalism A Cornerstone of Innovation and Medical Education at Scholl College of Podiatric Medicine.

In 1912, the Illinois College of Chiropody and Orthopedics was founded, and is today known as the Dr. William M. Scholl College of Podiatric Medicine. It has been an integral part of Rosalind Franklin University of Medicine and Science in North Chicago, Illinois since 2001. Through the ensuing decades, Scholl College alumni have been instrumental in moving the profession forward.

Feasibility and Efficacy of a Smart Mat Technology to Predict Development of Diabetic Plantar Ulcers.

OBJECTIVE: We conducted a multicenter evaluation of a novel remote foot-temperature monitoring system to characterize its accuracy for predicting impending diabetic foot ulcers (DFU) in a cohort of patients with diabetes with previously healed DFU. RESEARCH DESIGN AND METHODS: We enrolled 132 participants with diabetes and prior DFU in this 34-week cohort study to evaluate a remote foot-temperature monitoring system (ClinicalTrials.gov Identifier NCT02647346). The study device was a wireless daily-use thermometric foot mat to assess plantar temperature asymmetries. The primary outcome of interest was development of nonacute plantar DFU, and the primary efficacy analysis was the accuracy of the study device for predicting the occurrence of DFU over several temperature asymmetry thresholds. RESULTS: Of the 129 participants who contributed evaluable data to the study, a total of 37 (28.7%) presented with 53 DFU (0.62 DFU/participant/year). At an asymmetry of 2.22°C, the standard threshold used in previous studies, the system correctly identified 97% of observed DFU, with an average lead time of 37 days and a false-positive rate of 57%. Increasing the temperature threshold to 3.20°C decreased sensitivity to 70% but similarly reduced the false-positive rate to 32% with approximately the same lead time of 35 days. Approximately 86% of the cohort used the system at least 3 days a week on average over the study. CONCLUSIONS: Given the encouraging study results and the significant burden of DFU, use of this mat may result in significant reductions in morbidity, mortality, and resource utilization.

Reactive oxygen species and bacterial biofilms in diabetic wound healing.

Chronic wounds are a common and debilitating complication for the diabetic population. It is challenging to study the development of chronic wounds in human patients; by the time it is clear that a wound is chronic, the early phases of wound healing have passed and can no longer be studied. Because of this limitation, mouse models have been employed to better understand the early phases of chronic wound formation. In the past few years, a series of reports have highlighted the importance of reactive oxygen species and bacterial biofilms in the development of chronic wounds in diabetics. We review these recent findings and discuss mouse models that are being utilized to enhance our understanding of these potentially important contributors to chronic wound formation in diabetic patients.

A Rare Case of Acroangiodermatitis Associated with a Congenital Arteriovenous Malformation (Stewart-Bluefarb Syndrome) in a Young Veteran: Case Report and Review of the Literature.

Acroangiodermatitis (AD) is a rare angioproliferative disease manifesting with cutaneous lesions clinically similar to Kaposi's sarcoma. AD is a benign hyperplasia of preexisting vasculature and may be associated with acquired or congenital arteriovenous malformations (AVM), or severe chronic venous insufficiency (because of hypostasis, elevated venous pressure, arteriovenous shunting). Stewart-Bluefarb syndrome is the rare syndrome in which AD is associated with a congenital AVM. We present the case of a young veteran with a painful, chronic nonhealing ulcer and ipsilateral popliteal artery occlusion likely because of trauma, who elected transmetatarsal amputation for symptomatic relief. A 24-year-old male veteran presented with a 5-year history of a nonhealing dorsal left foot ulcer, resulting from a training exercise injury. He ultimately developed osteomyelitis requiring antibiotics, frequent debridements, multiple trials of unsuccessful skin substitute grafting, and severe unremitting pain. He noted a remote history of left digital deformities treated surgically as a child, and an AVM, previously endovascularly treated at an outside facility. Arterial duplex revealed somewhat dampened left popliteal, posterior tibial (PT), and dorsalis pedis (DP) artery signals with arterial brachial index of 1.0. CT angiography showed occlusion of the proximal to mid popliteal artery with significant calcifications felt initially to be a result of prior trauma. Pedal pulses were palpable and transcutaneous oxygen measurements revealed adequate oxygenation. Because of unremitting pain, the patient opted for amputation. Pathology revealed vascular proliferation consistent with AD. This case illustrates an unusual diagnosis of acroangiodermatitis, and a rare syndrome when associated with his underlying AVM (Stewart-Bluefarb syndrome). This resulted in a painful, chronic ulcer and was further complicated by trauma-related arterial occlusive disease. AD disease can hinder wound healing even in the presence of clinically evident blood flow. Although rare, such unusual diagnoses should be entertained particularly in the unusually young vascular surgical patient.

Topical platelet-derived growth factor vs placebo therapy of diabetic foot ulcers offloaded with windowed casts: a randomized, controlled trial.

OBJECTIVE: This study sought to compare the efficacy of topical platelet derived growth factor (Regranex, Smith and Nephew, London, UK) (test group) to placebo (control group) in treating diabetic foot ulcers. All subjects had a short leg walking cast with a window fashioned in the cast over the site of the ulcer. METHODS: Forty-six subjects were randomized (double-blind) 1:1 to the test or control group and treated for up to 4 months. Subjects had Wagner grade I ulcers with wound area of 1 cm2 to 16 cm2 without severe peripheral arterial disease, osteomyelitis, or any infection requiring antibiotics. Study medication was applied daily and casts changed approximately every 14 days. RESULTS: Of the 46 subjects randomized, 38 either healed or completed 16 weeks of therapy without healing. Eight subjects dropped out prior to 16 weeks. Based on intention-to-treat, 12 of 23 (52%) test group subjects healed before 16 weeks compared to 13 of 23 (57%) control group subjects (not significant). Regression analysis demonstrated that slower healing was associated with larger initial wound size (hazard radio [HR] = 0.997, 95% confidence interval [CI]: 0.995-1.00, P = 0.028) and excessive wound drainage (HR = 0.346, 95% CI: 0.126-0.948, P = 0.039). Excluding the patients who dropped out, 25 of 38 (66%) subjects healed by 4 months. Three additional subjects healed with casts that were worn longer than 4 months, for an overall rate of 74% at 9 months. Five subjects developed cast burns, and 3 patients required amputation. CONCLUSION: Topical platelet derived growth factor does not appear to significantly improve healing of Wagner grade I diabetic foot ulcers that are treated by offloading with a short leg walking cast. Excellent healing rates may be achieved with casting alone.

Monitoring temporal development and healing of diabetic foot ulceration using hyperspectral imaging.

This study combines non-invasive hyperspectral imaging with an experimentally validated skin optical model and inverse algorithm to monitor diabetic feet of two representative patients. It aims to observe temporal changes in local epidermal thickness and oxyhemoglobin concentration and to gain insight into the progression of foot ulcer formation and healing. Foot ulceration is a debilitating comorbidity of diabetes that may result in loss of mobility and amputation. Inflammation and necrosis preempt ulceration and can result in changes in the skin prior to ulceration and during ulcer healing that affect oxygen delivery and consumption. Previous studies estimated oxyhemoglobin and deoxyhemoglobin concentrations around pre-ulcerative and ulcer sites on the diabetic foot using commercially available hyperspectral imaging systems. These measurements were successfully used to detect tissue at risk of ulceration and predict the healing potential of ulcers. The present study shows epidermal thickening and decrease in oxyhemoglobin concentration can also be detected prior to ulceration at pre-ulcerative sites. The algorithm was also able to observe reduction in the epidermal thickness combined with an increase in oxyhemoglobin concentration around the ulcer as it healed and closed. This methodology can be used for early prediction of diabetic foot ulceration in a clinical setting.

Assessing diabetic foot ulcer development risk with hyperspectral tissue oximetry.

Foot ulceration remains a serious health concern for diabetic patients and has a major impact on the cost of diabetes treatment. Early detection and preventive care, such as offloading or improved hygiene, can greatly reduce the risk of further complications. We aim to assess the use of hyperspectral tissue oximetry in predicting the risk of diabetic foot ulcer formation. Tissue oximetry measurements are performed during several visits with hyperspectral imaging of the feet in type 1 and 2 diabetes mellitus subjects that are at risk for foot ulceration. The data are retrospectively analyzed at 21 sites that ulcerated during the course of our study and an ulceration prediction index is developed. Then, an image processing algorithm based on this index is implemented. This algorithm is able to predict tissue at risk of ulceration with a sensitivity and specificity of 95 and 80%, respectively, for images taken, on average, 58 days before tissue damage is apparent to the naked eye. Receiver operating characteristic analysis is also performed to give a range of sensitivity/specificity values resulting in a Q-value of 89%.

Hyperspectral imaging in diabetic foot wound care.

Diabetic foot ulceration is a major complication of diabetes and afflicts as many as 15 to 25% of type 1 and 2 diabetes patients during their lifetime. If untreated, diabetic foot ulcers may become infected and require total or partial amputation of the affected limb. Early identification of tissue at risk of ulcerating could enable proper preventive care, thereby reducing the incidence of foot ulceration. Furthermore, noninvasive assessment of tissue viability around already formed ulcers could inform the diabetes caregiver about the severity of the wound and help assess the need for amputation. This article reviews how hyperspectral imaging between 450 and 700 nm can be used to assess the risk of diabetic foot ulcer development and to predict the likelihood of healing noninvasively. Two methods are described to analyze the in vivo hyperspectral measurements. The first method is based on the modified Beer-Lambert law and produces a map of oxyhemoglobin and deoxyhemoglobin concentrations in the dermis of the foot. The second is based on a two-layer optical model of skin and can retrieve not only oxyhemoglobin and deoxyhemoglobin concentrations but also epidermal thickness and melanin concentration along with skin scattering properties. It can detect changes in the diabetic foot and help predict and understand ulceration mechanisms.

Wound inflammatory index: a "proof of concept" study to assess wound healing trajectory.

Diabetes around the globe results in one major limb amputation every 30 seconds, over 2500 limbs lost per day. The underlying pathophysiology sometimes leads to a chronic inflammatory stage, which may prevent appropriate healing, and therefore, the need for a clear strategy for assessing and classifying wounds and wound healing cannot be overstated. Temperature is a surrogate marker for inflammation. Quantitative thermography using a numerical index provides a useful way to assess wound healing. Advances in technology have afforded the availability of low-cost, high-resolution thermal imaging systems, which can be used to quantify sensitive changes on the skin surface and may be particularly useful to develop monitoring strategies for wounds. This article provides a standardized technique for calculating a thermal index (TI) supported with a case report from assessment of a diabetic foot ulcer. In this single case study, the TI/wound inflammatory index indicates a shift from negative to positive (p < .05) before it reaches zero.

Evaluation of diabetic foot ulcer healing with hyperspectral imaging of oxyhemoglobin and deoxyhemoglobin.

OBJECTIVE: Foot ulceration remains a major health problem for diabetic patients and has a major impact on the cost of diabetes treatment. We tested a hyperspectral imaging technology that quantifies cutaneous tissue hemoglobin oxygenation and generated anatomically relevant tissue oxygenation maps to assess the healing potential of diabetic foot ulcers (DFUs). RESEARCH DESIGN AND METHODS: A prospective single-arm blinded study was completed in which 66 patients with type 1 and type 2 diabetes were enrolled and followed over a 24-week period. Clinical, medical, and diabetes histories were collected. Transcutaneous oxygen tension was measured at the ankles. Superficial tissue oxyhemoglobin (oxy) and deoxyhemoglobin (deoxy) were measured with hyperspectral imaging from intact tissue bordering the ulcer. A healing index derived from oxy and deoxy values was used to assess the potential for healing. RESULTS: Fifty-four patients with 73 ulcers completed the study; at 24 weeks, 54 ulcers healed while 19 ulcers did not heal. When using the healing index to predict healing, the sensitivity was 80% (43 of 54), the specificity was 74% (14 of 19), and the positive predictive value was 90% (43 of 48). The sensitivity, specificity, and positive predictive values increased to 86, 88, and 96%, respectively, when removing three false-positive osteomyelitis cases and four false-negative cases due to measurements on a callus. The results indicate that cutaneous tissue oxygenation correlates with wound healing in diabetic patients. CONCLUSIONS: Hyperspectral imaging of tissue oxy and deoxy may predict the healing of DFUs with high sensitivity and specificity based on information obtained from a single visit.

In vivo time-resolved autofluorescence measurements to test for glycation of human skin.

We present an evaluation of time-resolved fluorescence measurements on human skin for screening type 2 diabetes. In vivo human skin is excited with a pulse diode at 375 nm and pulse width of 700 ps. Fluorescence decays are recorded at four different emission wavelengths: 442, 460, 478, and 496 nm. Experiments are performed at various locations, including the palms, arms, legs, and cheeks of a healthy Caucasian subject to test single-subject variability. The fluorescence decays obtained are modeled using a three-exponential decay. The variations in the lifetimes and amplitudes from one location to another are minimal, except on the cheek. We compare the fluorescent decays of 38 diabetic subjects and 37 nondiabetic subjects, with different skin complexions and of ages ranging from 6 to 85 yr. The average lifetimes for nondiabetic subjects were 0.5, 2.6, and 9.2 ns with fractional amplitudes of 0.78, 0.18, and 0.03, respectively. The effects of average hemoglobin A1c (HbA1c) from the previous 4 yr and diabetes duration are evaluated. While no significant differences between the fluorescence lifetimes of nondiabetic and diabetic subjects are observed, two of the fractional amplitudes are statistically different. Additionally, none of the six fluorescence parameters correlated with diabetes duration or HbA1c. One of the lifetimes as well as two of the fractional amplitudes differ between diabetic subjects with foot ulcers and nondiabetic subjects.

Evaluating and minimizing cardiac risk in surgical patients.

Cardiovascular complications are a major cause of postoperative morbidity and mortality. Proper assessment of risk and subsequent interventions can help diminish these complications. Assessing the patient's risk is based on the type of surgery performed and on individual patient characteristics. The latter can be established with a thorough history and physical, laboratory testing, risk indices, and cardiology studies.

Location of plantar ulcerations in diabetic patients referred to a Department of Veterans Affairs podiatry clinic.

This study described the location of foot ulcerations via a retrospective chart review of diabetic patients in a Department of Veterans Affairs podiatry clinic and correlated location of ulceration with specific medical parameters. The heel was a site of ulceration in 11% of the patients. By multiple logistic regression, patients with diminished vascular function were more than five times more likely to have heel ulceration than patients with adequate vascular status. The findings suggest that heel ulcerations are more common than originally thought and are associated with diminished vascular status. Further work is necessary for reducing plantar heel pressure in individuals who are not presently candidates for vascular interventions.

Effects of footwear on medial compartment knee osteoarthritis.

This pilot study investigated whether lateral-wedge insoles inserted into shock-absorbing walking shoes altered joint pain, stiffness, and physical function in patients with symptomatic medial compartment knee osteoarthritis (OA). Twenty-eight subjects wore full-length lateral-wedge insoles with an incline of 4 degrees in their walking shoes for 4 weeks. Pain, stiffness, and functional status were measured with the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index at baseline and 4 weeks postintervention. Significant improvements were observed in all three WOMAC subscales (pain, stiffness, and function). Pain scores were significantly reduced for the most challenging activity-stair climbing. Subjects wore insoles daily and tolerated them well. The results of this study indicated that lateral-wedge insoles inserted into shock-absorbing walking shoes are an effective treatment for medial compartment knee OA.

The top 10 things foot and ankle specialists wish every primary care physician knew.

Foot and ankle problems are common complaints of patients presenting to primary care physicians. These problems range from minor disorders, such as ankle sprains, plantar fasciitis, bunions, and iIngrown toenails, to more serious conditions such as Charcot arthropathy and Achilles tendon rupture. Early recognition and treatment of foot and ankle problems are imperative to avoid associated morbidities. Primary care physicians can address many of these complaints successfully but should be cognizant of which patients should be referred to a foot and ankle specialist to prevent common short-term and long-term complications. This article provides evidence-based pearls to assist primary care physicians in providing optimal care for their patients with foot and ankle complaints.