In contrast to the narrow indications for living skin equivalents, extracellular matrix biomaterials are clinically used in a wide range of wound-healing applications. Given the breadth of possible uses, the goal of this study was to retrospectively compile and analyze the clinical application and effectiveness of an extracellular matrix biomaterial derived from fetal bovine dermis (PriMatrix; TEI Biosciences, Boston, Massachusetts) in patients treated by a single physician and monitored postsurgically in an outpatient wound care center.
A retrospective medical record review was conducted of consecutive patients treated from January 2007 through January 2009 with meshed PriMatrix after sharp/surgical debridement and coverage with standard moist wound therapy dressings.
Twenty-nine patients and 34 wounds were compiled. All of the wounds were unresponsive to conservative treatment owing to complications, including infection, exposed bone or tendon, and other comorbidities known to delay healing. Wounds included 11 diabetic ulcers, 8 venous stasis ulcers, 10 nonhealing traumatic wounds, and 5 other chronic wounds. Thirty of 34 wounds healed, with four patients lost to follow-up. Mean time to healing for diabetic foot ulcers was 105 days with an average of 2.6 PriMatrix applications. Mean time to healing for venous, traumatic, and other chronic wounds was 74 to 82 days with an average of 1.2 to 1.4 PriMatrix applications.
In patients with comorbidities known to delay healing, the implantation of PriMatrix promoted the healing and, ultimately, full reepithelialization of otherwise unresponsive wounds of varied etiology, including those with complications of infection or exposed bone or tendon. (J Am Podiatr Med Assoc 102(3): 223–232, 2012)
Background: Off-loading excessive pressure is essential to healing diabetic foot ulcers. However, many patients are not compliant in using prescribed footwear or off-loading devices. We sought to validate a method of objectively measuring off-loading compliance via activity monitors.
Methods: For 4 days, a single subject maintained a written compliance diary concerning use of a removable cast walker. He also wore a hip-mounted activity monitor during all waking hours. An additional activity monitor remained mounted on the cast walker at all times. At the conclusion of the 4 days, the time-stamped hip activity data were independently coded for walker compliance by the compliance diary and by using the time-stamped walker activity data.
Results: An intraclass reliability of 0.93 was found between diary-coded and walker monitor–coded activity.
Conclusions: These results support the use of this dual activity monitor approach for assessing off-loading compliance. An advantage of this approach versus a patient-maintained diary is that the monitors are not susceptible to incorrect patient recall or a patient’s desire to please a caregiver by reporting inflated compliance. Furthermore, these results seem to lend support to existing reports in the literature using similar methods. (J Am Podiatr Med Assoc 99(2): 100–103, 2009)
Background: Chronic, nonhealing wounds are a growing health-care problem in the United States, affecting more than 6.5 million patients annually and costing the health-care system over $25 billion. Chronic wounds, including diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs), are often difficult to treat, and patients commonly fail to heal even with the most advanced therapies. The present study was designed to evaluate the efficacy and utility of the synthetic hybrid-scale fiber matrix in the treatment of complex chronic nonhealing lower-extremity ulcers refractory to advanced therapies.
Methods: A retrospective analysis of 20 patients with a total of 23 wounds (DFUs, n = 18; VLUs, n = 5) who underwent treatment using the synthetic hybrid-scale fiber matrix was conducted. The majority of ulcers (78%) included in this study were refractory to one or multiple previous advanced wound therapies and therefore considered difficult-to-heal ulcers with high failure risk for future therapies.
Results: Subjects had a mean wound age of 16 months and presented with 132 secondary comorbidities and 65 failed interventions and therapies. Treatment of VLUs with the synthetic matrix resulted in complete closure of 100% of the wounds over 244 ± 153 days with an average of 10.8 ± 5.5 applications. Treatment of DFUs with the synthetic matrix resulted in complete closure of 94% of the wounds over 122 ± 69 days with 6.7 ± 3.9 applications.
Conclusions: Treatment with the synthetic hybrid-scale fiber matrix resulted in the closure of 96% of complex chronic ulcers refractory to existing therapies. The inclusion of the synthetic hybrid-scale fiber matrix in wound care programs provides a critical and needed solution for costly, long-standing refractory wounds.
Osteomyelitis is one of the most feared sequelae of diabetic foot ulceration, which often leads to lower-extremity amputation and disability. Early diagnosis of osteomyelitis increases the likelihood of successful treatment and may limit the amount of bone resected, preserving ambulatory function. Although a variety of techniques exist for imaging the diabetic foot, standard radiography is still the only in-office imaging modality used today. However, radiographs lack sensitivity and specificity, making it difficult to diagnose bone infection at its early stages. In this report, we describe our initial experience with a cone beam computed tomography (CBCT)–based device, which may serve as an accurate and readily available tool for early diagnosis of osteomyelitis in a patient with diabetes. Two patients with infected diabetic foot ulcers were evaluated for osteomyelitis using radiography and CBCT. Positive imaging findings were confirmed by bone biopsy. In both patients, CBCT captured early osteolytic changes that were not apparent on radiographs, leading to early surgical intervention and successful treatment. The CBCT was helpful in facilitating detection and early clinical intervention for osteomyelitis in two diabetic patients with foot ulcers. These results are encouraging and warrant future evaluation.
Is TCC-EZ a Suitable Alternative to Gold Standard Total-Contact Casting?
A Plantar Pressure Analysis
The total-contact cast (TCC) is the gold standard for off-loading diabetic foot ulcers (DFUs) given its nonremovable nature. However, this modality remains underused in clinical settings due to the time and experience required for appropriate application. The TCC-EZ is an alternative off-loading modality marketed as being nonremovable and having faster and easier application. This study aims to investigate the potential of the TCC-EZ to reduce foot plantar pressures.
Twelve healthy participants (six males, six females) were fitted with a removable cast walker, TCC, TCC-EZ, and TCC-EZ with accompanying brace removed. These off-loading modalities were tested against a control. Pedar-X technology measured peak plantar pressures in each condition. Statistical analysis of four regions of the foot (rearfoot, midfoot, forefoot, and hallux) was conducted with Friedman and Wilcoxon signed rank tests. Significance was set at P < .05.
All of the off-loading conditions significantly reduced pressure compared with the control, except the TCC-EZ without the brace in the hallux region. There was no statistically significant difference between TCC-EZ and TCC peak pressure in any foot region. The TCC-EZ without the brace obtained significantly higher peak pressures than with the brace. The removable cast walker produced similar peak pressure reduction in the midfoot and forefoot but significantly higher peak pressures in the rearfoot and hallux.
The TCC-EZ is a viable alternative to the TCC. However, removal of the TCC-EZ brace results in minimal plantar pressure reduction, which might limit clinical applications of the TCC-EZ.
Background: Several studies have shown a significant relationship between depressive symptoms and wound healing, but these studies have not assessed the effects of depressive symptoms on diabetic foot prognosis. We specifically designed our study to assess the role of depressive symptoms in healing and recurrence of diabetic foot ulcers.
Methods: A consecutive series of 80 type 2 diabetic patients aged 60 years and older with foot ulcers was enrolled in a cohort observational study with a 6-month follow-up. Patients who healed within 6 months of enrollment were included in a 12-month follow-up study for assessment of ulcer recurrence. Depressive symptoms were assessed with the geriatric depression scale.
Results: Healing was associated with a smaller ulcer area, shorter delay between ulcer onset and treatment, lower glycosylated hemoglobin, and higher ankle-brachial index. Both smoking status and Texas and Wagner scores also had a significant impact on healing. Patients who healed had significantly lower scores on the geriatric depression scale, and those with scores = 10 had a significantly higher risk of not healing at 6 months (relative risk, 3.57; 95% confidence interval, 1.05–12.2). Patients with a recurrent ulcer (59.3%) showed significantly higher total cholesterol levels, higher scores on the Greenfield index of disease severity and geriatric depression scale, and a higher prevalence of cerebrovascular disease. Depressive symptoms maintained a significant association with persistence and recurrence of ulcer even after adjustment for confounders.
Conclusions: Depressive symptoms are associated with impaired healing and recurrence of ulcers in elderly type 2 diabetic patients. (J Am Podiatr Med Assoc 98(2): 130–136, 2008)
Recognizing the Prevalence of Changing Adult Foot Size
An Opportunity to Prevent Diabetic Foot Ulcers?
Ill-fitting shoes may precipitate up to half of all diabetes-related amputations and are often cited as a leading cause of diabetic foot ulcers (DFU), with those patients being 5 to 10 times more likely to present wearing improperly fitting shoes. Among patients with prior DFU, those who self-select their shoe wear are at a three-fold risk for reulceration at 3 years versus those patients wearing prescribed shoes. Properly designed and fitted shoes should then address much of this problem, but evidence supporting the benefit of therapeutic shoe programs is inconclusive. The current study, performed in a male veteran population, is the first such effort to examine the prevalence and extent of change in foot length affecting individuals following skeletal maturity. Nearly half of all participants in our study experienced a ≥1 shoe size change in foot length during adulthood. We suggest that these often unrecognized changes may explain the broad use of improperly sized shoe wear, and its associated sequelae such as DFU and amputation. Regular clinical assessment of shoe fit in at-risk populations is therefore also strongly recommended as part of a comprehensive amputation prevention program.
Osteomyelitis is a common complication in the diabetic foot that can conclude with amputation. The purpose of this study was to evaluate the role of diffusion-weighted magnetic resonance imaging (DWI) in the diagnosis of osteomyelitis in diabetic foot ulcer (DFU).
Thirty patients with type 2 diabetes mellitus and a DFU were enrolled. Both DWIs and conventional MRIs were obtained. Apparent diffusion coefficient (ADC) measurements were made by transferring the images to a workstation. The measurements were made both from bone with osteomyelitis, or nearest to the injured area if osteomyelitis is not available, and from the adjacent soft tissue.
The patients comprised nine women (30%) and 21 men (70%) with a mean age of 58.7 years (range, 41–78 years). The levels of ADC were significantly low (P = .022) and the erythrocyte sedimentation rates were significantly high (P = .014) in patients with osteomyelitis (n = 9) compared with patients without osteomyelitis (n = 21). The mean ± SD bone ADC value (0.75 ± 0.16 × 10–3 mm2/sec) was significantly lower than the adjacent soft-tissue ADC value (0.90 ± 0.15 × 10–3 mm2/sec) in patients with osteomyelitis (P = .04).
It is suggested that DWI contributes to conventional MRI with short imaging time and no requirement for contrast agent. Therefore, DWI may be an alternative diagnostic method for the evaluation of DFU and the detection of osteomyelitis.
Digestion of collagen with clostridial collagenase (CC) produces peptides that can induce cellular responses consistent with wound healing in vivo. However, nonhealing human wounds are typically in a state of chronic inflammation. We evaluated the effects of CC on markers of inflammation in cell culture and wound fluid from diabetic patients.
Lipopolysaccharide-induced release of tumor necrosis factor-α and interleukin-6 from interferon-γ–activated THP-1 monocytes was measured in the presence or absence of CC or CC collagen digests. In the clinical study, 17 individuals with mildly inflamed diabetic foot ulcers were randomized to receive CC ointment (CCO) or hydrogel. Weekly assessments included wound appearance and measurements. Wound exudate was collected at baseline and at 2 and 4 weeks of treatment. A multiplex assay was used to measure levels of analytes, including those associated with inflammation and with inflammation resolution.
Lower levels of tumor necrosis factor-α and interleukin-6 were found in media of cells cultured with CC or CC digests of collagen type I or III than for untreated lipopolysaccharide controls (P < .05). Clinically, CCO and hydrogel resulted in improvement in wound appearance and a decrease in mean wound area. The CCO, but not the hydrogel, was found to increase the level of analytes associated with resolution of inflammation while decreasing those associated with inflammation. There was a general correlation between resolution of inflammation and healing.
These results support a hypothesis that debridement with CCO is associated with decreased inflammation and greater progress toward healing.
Retrospective and prospective studies have shown that elevated plantar pressure is a causative factor in the development of many plantar ulcers in diabetic patients and that ulceration is often a precursor of lower-extremity amputation. Herein, we review the evidence that relieving areas of elevated plantar pressure (off-loading) can prevent and heal plantar ulceration.
There is no consensus in the literature concerning the role of off-loading through footwear in the primary or secondary prevention of ulcers. This is likely due to the diversity of intervention and control conditions tested, the lack of information about off-loading efficacy of the footwear used, and the absence of a target pressure threshold for off-loading. Uncomplicated plantar ulcers should heal in 6 to 8 weeks with adequate off-loading. Total-contact casts and other nonremovable devices are most effective because they eliminate the problem of nonadherence to recommendations for using a removable device. Conventional or standard therapeutic footwear is not effective in ulcer healing. Recent US and European surveys show that there is a large discrepancy between guidelines and clinical practice in off-loading diabetic foot ulcers. Many clinics continue to use methods that are known to be ineffective or that have not been proved to be effective while ignoring methods that have demonstrated efficacy.
A variety of strategies are proposed to address this situation, notably the adoption and implementation of recently established international guidelines, which are evidence based and specific, by professional societies in the United States and Europe. Such an approach would improve the often poor current expectations for healing diabetic plantar ulcers. (J Am Podiatr Med Assoc 100(5): 360–368, 2010)