The clinical diagnosis of osteomyelitis is difficult because of neuropathy, vascular disease, and immunodeficiency; also, with no established consensus on the diagnosis of foot osteomyelitis, the reported efficacy of magnetic resonance imaging (MRI) in detecting osteomyelitis and distinguishing it from reactive bone marrow edema is unclear. Herein, we describe a retrospective study on the efficacy of MRI for decision-making accuracy in diagnosing osteomyelitis in diabetic foot ulcers.
Twelve diabetic patients with infected foot ulcers underwent preoperative MRI between January 1, 2008, and December 31, 2011. The findings were compared with the histopathologic features of 67 parts of 45 resected bones, the cut ends of which were also histopathologically evaluated.
Osteomyelitis was disclosed by MRI and histopathologically confirmed in 30 parts. In contrast, bone marrow edema diagnosed by MRI in 29 parts was confirmed in 23; the other six parts displayed osteomyelitis. Among 17 resected bones, 13 cut ends displayed bone marrow edema and four were normal. All of the wounds healed uneventfully.
In the diagnosis of diabetic foot ulcers, osteomyelitis is often reliably distinguished from reactive bone marrow edema, except in special cases.
Introduction: A study of 72 subjects conducted in the European Union and Australia assessed the safety and efficacy of Apligraf (Organogenesis, Inc, Canton, Massachusetts), a bilayered cell therapy composed of living keratinocytes and living fibroblasts in the treatment of non-infected, diabetic foot ulcers (DFU). The design and patient population of this study were similar to a 208-subject United States study (Veves et al., 2001), which led to FDA approval of Apligraf for the treatment of DFU. EU patient outcomes were compared and contrasted to established US-based patient outcome parameters.
Methods: Subjects with a non-infected neuropathic diabetic foot ulcer present for at least two weeks were enrolled in these prospective, multicenter, randomized, controlled, open-label studies that compared Apligraf used in conjunction with standard therapy (sharp debridement, standard wound care, and off-loading) against standard therapy alone.
Results: The design, conduct, and patient populations of the EU and US studies were comparable. Pooling of data was able to be performed because of the similarity and consistency of the two studies. Efficacy and safety results remained consistent across studies independent of mean ulcer duration that was significantly longer in the EU study (21 months, compared to 10 months in the US). Reported adverse events through 12 weeks were comparable across treatment groups in the two studies. Multiple efficacy measures consistently demonstrated superiority of Apligraf treatment over control treated groups in both studies. Combining the data from both studies, 55.2% (80/145) of Apligraf subjects had complete would closure by 12 weeks, compared to 34.3% (46/134) of Control subjects (P = 0.0005; Fisher3s exact test), and Apligraf subjects had a significantly shorter time to complete wound closure (P = 0.0004; log-rank test).
Conclusions: Both the EU and US studies exhibited superior efficacy and comparable safety for subjects treated with Apligraf compared to control treated subjects. The similar outcomes of the two studies provide robust, consistent evidence of the benefit of Apligraf in treating geographically disparate DFU patient populations.
The increasing resistance of bacteria to antibiotics and the frequency of comorbid conditions of patients make the treatment of diabetic foot infections problematic. In this context, photodynamic therapy could be a useful tool to treat infected wounds. The aim of this study was to evaluate the effect of repeated applications of a phthalocyanine derivative (RLP068) on the bacterial load and on the healing process.
The present analysis was performed on patients with clinically infected ulcers who had been treated with RLP068. A sample for microbiological culture was collected at the first visit before and immediately after the application of RLP068 on the ulcer surface, and the area was illuminated for 8 minutes with a red light. The whole procedure was repeated three times per week at two centers (Florence and Arezzo, Italy) (sample A), and two times per week at the third center (Stuttgart, Germany) (sample B) for 2 weeks.
Sample A and sample B were composed of 55 and nine patients, respectively. In sample A, bacterial load decreased significantly after a single treatment, and the benefit persisted for 2 weeks. Similar effects of the first treatment were observed in sample B. In both samples, the ulcer area showed a significant reduction during follow-up, even in patients with ulcers infected with gram-negative germs or with exposed bone.
RLP068 seems to be a promising topical wound management procedure for the treatment of infected diabetic foot ulcers.
Diabetic Foot Ulcers Treated with Becaplermin and TheraGauze, a Moisture-Controlling Smart Dressing
A Randomized, Multicenter, Prospective Analysis
Background: It is hypothesized that moisture regulation specific to the area of contact results in local wound conditions more amenable to healing, which would result in faster and more frequent wound closure. TheraGauze is a new polymer-impregnated dressing designed to regulate moisture to a varying degree over the entire surface of a wound.
Methods: This prospective, randomized, multicenter study examined outcomes from treatment of diabetic foot ulcers with TheraGauze and TheraGauze in conjunction with becaplermin. We also compared these outcomes with historical data from the literature that used saline-moistened gauze and becaplermin.
Results: The rates of wound closure with TheraGauze and TheraGauze + becaplermin were 0.37 and 0.41 cm2/week, respectively (P = .34). The difference between these values was not statistically significant. We also observed high closure rates at 12 weeks (46.2% in both groups) and 20 weeks (61.5% with TheraGauze alone and 69.2% with TheraGauze + becaplermin). These data were also compared with historical data for closure rates (0.18 cm2/week) and percentage of wounds closed using saline-moistened gauze alone and becaplermin with saline-moistened gauze (0.24 cm2/week) from a variety of studies.
Conclusions: Wounds in which moisture content was regulated with TheraGauze showed more rapid change in wound area and a higher percentage of wounds achieving closure at 12 and 20 weeks regardless of whether becaplermin was used. (J Am Podiatr Med Assoc 100(3): 155–160, 2010)
Offloading devices for diabetic foot ulcers (DFU) generally restrict exercise. In addition to traditional health benefits, exercise could benefit DFU by increasing blood flow and acting as thermotherapy. This study functionally evaluated a cycling cleat designed for forefoot DFU.
Fifteen individuals at risk of developing a DFU used a recumbent stationary bicycle to complete one 5-minute cycling bout with the DFU cleat on their study foot and one 5-minute bout without it. Foot stress was evaluated by plantar pressure insoles during cycling. Laser Doppler perfusion monitored blood flow to the hallux. Infrared photographs measured foot temperature before and after each cycling bout.
The specialized cleat significantly reduced forefoot plantar pressure (9.9 kPa versus 62.6 kPa, P < .05) and pressure time integral (15.4 versus 76.4 kPa*sec, P < .05). Irrespective of footwear condition, perfusion to the hallux increased (3.97 ± 1.2 versus 6.9 ± 1.4 tissue perfusion units, P < .05) after exercise. Infrared images revealed no changes in foot temperature.
The specialized cleat allowed participants to exercise with minimal forefoot stress. The observed increase in perfusion suggests that healing might improve if patients with active DFU were to use the cleat. Potential thermotherapy for DFU was not supported by this study. Evaluation of the device among individuals with active DFU is now warranted.
Background: We sought to examine the economic value of specialized lower-extremity medical care by podiatric physicians in the treatment of diabetic foot ulcers by evaluating cost outcomes for patients with diabetic foot ulcer who did and did not receive care from a podiatric physician in the year before the onset of a foot ulcer.
Methods: We analyzed the economic value among commercially insured patients and Medicare-eligible patients with employer-sponsored supplemental medical benefits using the MarketScan Databases. The analysis consisted of two parts. In part I, we examined cost or savings per patient associated with care by podiatric physicians using propensity score matching and regression techniques; in part II, we extrapolated cost or savings to populations.
Results: Matched and regression-adjusted results indicated that patients who visited a podiatric physician had $13,474 lower costs in commercial plans and $3,624 lower costs in Medicare plans during 2-year follow-up (P < .01 for both). A positive net present value of increasing the share of patients at risk for diabetic foot ulcer by 1% was found, with a range of $1.2 to $17.7 million for employer-sponsored plans and $1.0 to $12.7 million for Medicare plans.
Conclusions: These findings suggest that podiatric medical care can reduce the disease and economic burdens of diabetes. (J Am Podiatr Med Assoc 101(2): 93–115, 2011)
This study investigated the resistance of bacteria isolated from diabetic foot ulcers (DFUs) to antibiotics frequently used in the management of the diabetic foot infections, at a range of pH values (pH 6.5, 7.5, and 8.5) known to exist in DFU wound fluid. This study aimed to determine whether changes (or atypical stasis) in wound fluid pH modulate the antibiotic resistance of DFU isolates, with potential implications in relation to the suppression/eradication of bacterial infections in DFUs.
Thirty bacterial isolates were recovered from DFU wound fluid, including Staphylococcus spp, Staphylococcus aureus, Escherichia coli, Streptococcus spp, Pseudomonas spp, and Pseudomonas aeruginosa. The resistances of these isolates to a panel of antibiotics currently used in the treatment of infected or potentially infected DFUs, ie, ciprofloxacin, amoxicillin-clavulanate, doxycycline, and piperacillin-tazobactam, at the previously mentioned pH values were determined by a modification of the Kirby-Bauer assay.
The resistance of DFU isolates to clinically relevant antibiotics was significantly affected by the pH levels in DFU wound fluid.
These findings highlight the importance of a more comprehensive understanding of the conditions in DFUs to inform clinical decision making in the selection and application of antibiotics in treating these difficult-to-heal wounds. The scale of the differences in the efficacies of antibiotics at the different pH values examined is likely to be sufficient to suggest reconsideration of the antibiotics of choice in the treatment of DFU infection.
People at risk for diabetic foot ulcer (DFU) often misunderstand why foot ulcers develop and what self-care strategies may help prevent them. The etiology of DFU is complex and difficult to communicate to patients, which may hinder effective self-care. Thus, we propose a simplified model of DFU etiology and prevention to aid communication with patients. The Fragile Feet & Trivial Trauma model focuses on two broad sets of risk factors: predisposing and precipitating. Predisposing risk factors (eg, neuropathy, angiopathy, and foot deformity) are usually lifelong and result in “fragile feet.” Precipitating risk factors are usually different forms of everyday trauma (eg, mechanical, thermal, and chemical) and can be summarized as “trivial trauma.” We suggest that the clinician consider discussing this model with their patient in three steps: 1) explain how a patient’s specific predisposing risk factors result in fragile feet for the rest of life, 2) explain how specific risk factors in a patient’s environment can be the trivial trauma that triggers development of a DFU, and 3) discuss and agree on with the patient measures to reduce the fragility of the feet (eg, vascular surgery) and prevent trivial trauma (eg, wear therapeutic footwear). By this, the model supports the communication of two essential messages: that patients may have a lifelong risk of ulceration but that there are health-care interventions and self-care practices that can reduce these risks. The Fragile Feet & Trivial Trauma model is a promising tool for aiding communication of foot ulcer etiology to patients. Future studies should investigate whether using the model results in improved patient understanding and self-care and, in turn, contributes to lower ulceration rates.
Diabetic foot ulcer (DFU) is a serious health problem. Major amputation increases the risk of mortality in patients with DFU; therefore, treatment methods other than major amputation come to the fore for these patients. Graft applications create an appropriate environment for the reproduction of epithelial cells. Similarly, epidermal growth factor (EGF) also stimulates epithelization and increases epidermis formation. In this study, we aimed to compare patients with DFU treated with EGF and those treated with a split-thickness skin graft.
Patients who were treated for DFU in the general surgery clinic were included in the study. The patients were evaluated retrospectively according to their demographic characteristics, wound characteristics, duration of treatment, and treatment modalities.
There were 26 patients in the EGF group and 21 patients in the graft group. The mean duration of treatment was 7 weeks (4-8 weeks) in the EGF group and 5.3 weeks (4-8 weeks) in the graft group (P < .05). In the EGF group, wound healing could not be achieved in one patient during the study period. In the graft group, no recovery was achieved in three patients (14.2%) in the donor site. Graft loss was detected in four patients (19%), and partial graft loss was observed in three patients (14.2%). The DFU of these patients were on the soles (85.7%). These patients have multiple comorbidities.
EGF application may be preferred to avoid graft complications in the graft area and the donor site, especially in elderly patients with multiple comorbidities and wounds on the soles.
Background: Multiple organizations have issued guidelines to address the prevention, diagnosis, and management of diabetic foot ulcers (DFUs) based on evidence review and expert opinion. We reviewed these guidelines to identify consensus (or lack thereof) on the nature of these recommendations, the strength of the recommendations, and the level of evidence.
Methods: Ovid, PubMed, Web of Science, Cochrane Library, and Embase were searched in October 2018 using the MESH term diabetic foot, the key word diabetic foot, and the filters guideline or practice guideline. To minimize recommendations based on older literature, guidelines published before 2012 were excluded. Articles without recommendations characterized by strength of recommendation and level of evidence related specifically to DFU were also excluded. A manual search for societal recommendations yielded no further documents. Recommendations were ultimately extracted from 12 articles. Strength of evidence and strength of recommendation were noted for each guideline recommendation using the Grading of Recommendations Assessment, Development, and Evaluation system or the Centre for Evidence-Based Medicine system. To address disparate grading systems, we mapped the perceived level of evidence and strength of recommendations onto the American Heart Association guideline classification schema.
Results: Recommendations found in two or more guidelines were collected into a clinical checklist characterized by strength of evidence and strength of recommendation. Areas for future research were identified among recommendations based on minimal evidence, areas of controversy, or areas of clinical care without recommendations.
Conclusions: Through this work we developed a multidisciplinary set of DFU guidelines stratified by strength of recommendation and quality of evidence, created a clinical checklist for busy practitioners, and identified areas for future focused research. This work should be of value to clinicians, guideline-issuing bodies, and researchers. We also formulated a method for the review and integration of guidelines issued by multiple professional bodies.