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An Assessment of Intralesional Epidermal Growth Factor for Treating Diabetic Foot Wounds
The First Experiences in Turkey
Background:
Intralesional epidermal growth factor (EGF) has been available as a medication in Turkey since 2012. We present the results of our experience using intralesional EGF in Turkey for patients with diabetic foot wounds.
Methods:
A total of 174 patients from 25 Turkish medical centers were evaluated for this retrospective study. We recorded the data on enrolled individuals on custom-designed patient follow-up forms. Patients received intralesional injections of 75 μg of EGF three times per week and were monitored daily for adverse reactions to treatment. Patients were followed up for varying periods after termination of EGF treatments.
Results:
Median treatment duration was 4 weeks, and median frequency of EGF administration was 12 doses. Complete response (granulation tissue >75% or wound closure) was observed in 116 patients (66.7%). Wounds closed with only EGF administration in 81 patients (46.6%) and in conjunction with various surgical interventions after EGF administration in 65 patients (37.3%). Overall, 146 of the wounds (83.9%) were closed at the end of therapy. Five patients (2.9%) required major amputation. Adverse effects were reported in 97 patients (55.7%).
Conclusions:
In patients with diabetic foot ulcer who received standard care, additional intralesional EGF application after infection control provided high healing rates with low amputation rates.
The Costs of Diabetic Foot
The Economic Case for the Limb Salvage Team
In 2007, the treatment of diabetes and its complications in the United States generated at least $116 billion in direct costs; at least 33% of these costs were linked to the treatment of foot ulcers. Although the team approach to diabetic foot problems is effective in preventing lower-extremity amputations, the costs associated with implementing a diabetic-foot–care team are not well understood. An analysis of these costs provides the basis for this report.
Diabetic foot problems impose a major economic burden, and costs increase disproportionately to the severity of the condition. Compared with diabetic patients without foot ulcers, the cost of care for those with foot ulcers is 5.4 times higher in the year after the first ulcer episode and 2.8 times higher in the second year. Costs for treating the highest-grade ulcers are 8 times higher than are those for treating low-grade ulcers. Patients with diabetic foot ulcers require more frequent emergency department visits and are more commonly admitted to the hospital, requiring longer lengths of stay. Implementation of the team approach to manage diabetic foot ulcers in a given region or health-care system has been reported to reduce long-term amputation rates 62% to 82%. Limb salvage efforts may include aggressive therapy such as revascularization procedures and advanced wound-healing modalities. Although these procedures are costly, the team approach gradually leads to improved screening and prevention programs and earlier interventions and, thus, seems to reduce long-term costs.
To date, aggressive limb preservation management for patients with diabetic foot ulcers has not usually been paired with adequate reimbursement. It is essential to direct efforts in patient-caregiver education to allow early recognition and management of all diabetic foot problems and to build integrated pathways of care that facilitate timely access to limb salvage procedures. Increasing evidence suggests that the costs of implementing diabetic foot teams can be offset in the long term by improved access to care and reductions in foot complications and amputation rates. (J Am Podiatr Med Assoc 100(5): 335–341, 2010)
BACKGROUND:Diabetic foot ulceration is a severe complication of diabetes characterized by chronic inflammation and impaired wound healing. This study aims to evaluate the effect of a medical device gel based on Adelmidrol + Trans traumatic acid in the healing process of diabetic foot ulcers. METHODS: Thirty-seven diabetic patients with foot ulcers of mild/moderate grade were treated with the gel applied daily for 4 weeks on the affected area. The following parameters were evaluated at baseline and weekly: a) wound area, measured drawing a map of the ulcer then calculated with Photoshop6 tools, b) clinical appearance of the ulcer, assessed recording the presence/absence of dry/wet necrosis, infection, fibrin, neoepithelium, exudate, redness, granulation tissue. RESULTS: Topical treatment led to progressive healing of diabetic foot ulcers with a significant reduction of the wound area and an improvement in the clinical appearance of the ulcers. No adverse events treatment-related were observed. CONCLUSIONS: The results of this open-label study show the potential benefits of Adelmidrol + Trans traumatic acid topical administration to promote re-epithelialization of diabetic foot ulcers. Further studies need to confirm the observed results.
Diabetic foot infections are a common and often serious problem, accounting for more hospital bed days than any other complication of diabetes. Despite advances in antibiotic drug therapy and surgical management, these infections continue to be a major risk factor for amputations of the lower extremity. Although a variety of wound size and depth classification systems have been adapted for use in codifying diabetic foot ulcerations, none are specific to infection. In 2003, the International Working Group on the Diabetic Foot developed guidelines for managing diabetic foot infections, including the first severity scale specific to these infections. The following year, the Infectious Diseases Society of America published their diabetic foot infection guidelines. Herein, we review some of the critical points from the Executive Summary of the Infectious Diseases Society of America document and provide a commentary following each issue to update the reader on any pertinent changes that have occurred since publication of the original document in 2004.
The importance of a multidisciplinary limb salvage team, apropos of this special issue jointly published by the American Podiatric Medical Association and the Society for Vascular Surgery, cannot be overstated. (J Am Podiatr Med Assoc 100(5): 395–400, 2010)
Antibiotic Tissue Penetration in Diabetic Foot Infections
A Review of the Microdialysis Literature and Needs for Future Research
Although many antimicrobial agents display good in vitro activity against the pathogens frequently implicated in diabetic foot infections, effective treatment can be complicated by reduced tissue penetration in this population secondary to peripheral arterial disease and emerging antimicrobial resistance, which can result in clinical failure. Improved characterization of antibiotic tissue pharmacokinetics and penetration ratios in diabetic foot infections is needed. Microdialysis offers advantages over the skin blister and tissue homogenate studies historically used to define antibiotic penetration in skin and soft-tissue infections by defining antibiotic penetration into the interstitial fluid over the entire concentration versus time profile. However, only a select number of agents currently recommended for treating diabetic foot infections have been evaluated using these methods, which are described herein. Better characterization of the tissue penetration of antibiotic agents is needed for the development of methods for maximizing the pharmacodynamic profile of these agents to ultimately improve treatment outcomes for patients with diabetic foot infections.
Background: The diabetic foot is one of the main complications of diabetes mellitus, with a high risk of minor or major amputation. The preclinical foot lesions of patients without foot complaints were compared with healthy controls and analyzed.
Methods: This study was conducted with 89 diabetic patients from an endocrinology clinic and 35 nondiabetic control patients. The patients were asked about the presence, types, and durations of pedal complaints; acquired and congenital foot deformities; and atrophy. Patient gaits were inspected for any swelling; skin and nail changes were also recorded. Ranges of articular motion, deformities, crepitations, and any painful perceptions were noted.
Results: The differences between groups were significant for sensorial defects, joint changes of the foot, nail abnormalities, and neuropathic changes.
Conclusions: Every patient with an established diagnosis of diabetes can be considered a potential sufferer of diabetic foot for whom medical therapy and foot protection programs are indicated. (J Am Podiatr Med Assoc 99(2): 114–120, 2009)
Osteolysis, caused by active resorption of bone matrix by osteoclasts, can be primary or can develop secondary to a variety of disease processes. An elevated level of inflammatory cytokines in the local milieu and increased blood flow secondary to infection or autonomic neuropathy stimulate the osteoclasts and cause bone loss in the diabetic foot. Charcot's neuroarthropathy and osteomyelitis are well-known foot complications of diabetes, and secondary osteolysis has largely been underappreciated and, hence, underreported. Plain radiographs, an initial component in the evaluation of the diabetic foot, may not successfully differentiate secondary osteolysis from osteomyelitis. We describe a patient with phalangeal osteolysis secondary to soft-tissue infection in whom a correct and timely diagnosis helped avoid unnecessary surgical interventions.
Surgical intervention for chronic deformities and ulcerations has become an important component in the management of patients with diabetes mellitus. Such patients are no longer relegated to wearing cumbersome braces or footwear for deformities that might otherwise be easily corrected. Although surgical intervention in these often high-risk individuals is not without risk, the outcomes are fairly predictable when patients are properly selected and evaluated. In this brief review, we discuss the rationale and indications for diabetic foot surgery, focusing on the surgical decompression of deformities that frequently lead to foot ulcers. (J Am Podiatr Med Assoc 100(5): 369–384, 2010)
Mortality Rates and Diabetic Foot Ulcers
Is it Time to Communicate Mortality Risk to Patients with Diabetic Foot Ulceration?
Five-year mortality rates after new-onset diabetic ulceration have been reported between 43% and 55% and up to 74% for patients with lower-extremity amputation. These rates are higher than those for several types of cancer including prostate, breast, colon, and Hodgkin’s disease. These alarmingly high 5-year mortality rates should be addressed more aggressively by patients and providers alike. Cardiovascular diseases represent the major causal factor, and early preventive interventions to improve life expectancy in this most vulnerable patient cohort are essential. New-onset diabetic foot ulcers should be considered a marker for significantly increased mortality and should be aggressively managed locally, systemically, and psychologically. (J Am Podiatr Med Assoc 98(6): 489–493, 2008)
Methicillin-Resistant Staphylococcus aureus Endocarditis from a Diabetic Foot Ulcer
Understanding and Mitigating the Risk
Diabetic foot infections are a common cause of morbidity and mortality in the United States, and successful treatment often requires an aggressive and prolonged approach. Recent work has elucidated the importance of appropriate therapy for a given severity of diabetic foot infection, and highlighted the ongoing risk such patients have for subsequent invasive life-threatening infection should diabetic foot ulcers fail to heal. The authors describe the case of a man with diabetes who had prolonged, delayed healing of a diabetic foot ulcer. The ulcer subsequently became infected by methicillin-resistant Staphylococcus aureus (MRSA). The infection was treated conservatively with oral therapy and minimal debridement. Several months later, he experienced MRSA bloodstream infection and complicating endocarditis. The case highlights the ongoing risk faced by patients when diabetic foot ulcers do not heal promptly, and emphasizes the need for aggressive therapy to promote rapid healing and eradication of MRSA.
