The aim of this pilot study was to determine the safety and potential benefit of adding a topical gentamicin-collagen sponge to standard of care (systemic antibiotic therapy plus standard diabetic wound management) for treating diabetic foot infections of moderate severity.
We randomized 56 patients with moderately infected diabetic foot ulcers in a 2:1 ratio to receive standard of care plus the gentamicin-collagen sponge (treatment group, n = 38) or standard of care only (control group, n = 18) for up to 28 days of treatment. Investigators performed clinical, microbiological, and safety assessments at regularly scheduled intervals and collected pharmacokinetic samples from patients treated with the gentamicin-collagen sponge. Test of cure was clinically assessed 14 days after all antibiotic therapy was stopped.
On treatment day 7, we noted clinical cure in no treatment patients and three control patients (P = .017). However, for evaluable patients at the test-of-cure visit, the treatment group had a significantly higher proportion of patients with clinical cure than did the control group (22 of 22 [100.0%] versus 7 of 10 [70.0%]; P =.024). Patients in the treatment group also had a higher rate of eradication of baseline pathogens at all visits (P ≤ .038) and a reduced time to pathogen eradication (P < .001). Safety data were similar for both groups.
Topical application of the gentamicin-collagen sponge seems safe and may improve clinical and microbiological outcomes of diabetic foot infections of moderate severity when combined with standard of care. These pilot data suggest that a larger trial of this treatment is warranted. (J Am Podiatr Med Assoc 102(3): 223-232, 2012)
This historical perspective highlights some of the pioneers, milestones, teams, and system changes that have had a major impact on management of the diabetic foot during the past 100 years. In 1934, American diabetologist Elliott P. Joslin noted that mortality from diabetic coma had fallen from 60% to 5% after the introduction of insulin, yet deaths from diabetic gangrene of the lower extremity had risen significantly. He believed that diabetic gangrene was preventable. His remedy was a team approach that included foot care, diet, exercise, prompt treatment of foot infections, and specialized surgical care.
The history of the team approach to management of the diabetic foot chronicles the rise of a new health profession—podiatric medicine and surgery—and emergence of the specialty of vascular surgery. The partnership among the diabetologist, vascular surgeon, and podiatric surgeon is a natural one. The complementary skills and knowledge of each can improve limb salvage and functional outcomes. Comprehensive multidisciplinary foot-care programs have been shown to increase quality of care and reduce amputation rates by 36% to 86%. Development of distal revascularization techniques to restore pulsatile blood flow to the foot has also been a major advancement.
Patients with diabetic foot complications are among the most complex and vulnerable of all patient populations. Specialized diabetic foot clinics of the 21st century should be multidisciplinary and equipped to coordinate diagnosis, off-loading, and preventive care; to perform revascularization procedures; to aggressively treat infections; and to manage medical comorbidities. (J Am Podiatr Med Assoc 100(5): 317–334, 2010)
Background: People with diabetic foot ulcers report poor quality of life. However, prospective studies that chart quality of life from the onset of diabetic foot ulcers are lacking. We describe change in quality of life in a cohort of people with diabetes and their first foot ulcer during 18 months and its association with adverse outcomes.
Methods: In this prospective cohort study of adults with their first diabetic foot ulcer, the main outcome was change in Medical Outcomes Study 36-Item Short Form Health Survey scores between baseline and 18-month follow-up. We recorded baseline demographics, diabetes characteristics, depression, and diabetic foot outcomes and mortality at 18 months.
Results: In 253 people with diabetes and their first ulcer, there were 40 deaths (15.8%), 36 amputations (15.5%), 99 recurrences (43.2%), and 52 nonhealing ulcers (21.9%). The 36-Item Short Form Health Survey response rate of survivors at 18 months was 78% (n = 157). There was a 5- to 6-point deterioration in mental component summary scores in people who did not heal (adjusted mean difference, −6.54; 95% confidence interval, −12.64 to −0.44) or had recurrent ulcers (adjusted mean difference, −5.30; 95% confidence interval, −9.87 to −0.73) and a nonsignificant reduction in those amputated (adjusted mean difference, −5.00; 95% confidence interval, −11.15 to 1.14).
Conclusions: Quality of life deteriorates in people with diabetes whose first foot ulcer recurs or does not heal within 18 months. (J Am Podiatr Med Assoc 99(5): 406–414, 2009)
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 diabetic Charcot foot syndrome is a serious and potentially limb-threatening lower-extremity complication of diabetes. First described in 1883, this enigmatic condition continues to challenge even the most experienced practitioners. Now considered an inflammatory syndrome, the diabetic Charcot foot is characterized by varying degrees of bone and joint disorganization secondary to underlying neuropathy, trauma, and perturbations of bone metabolism. An international task force of experts was convened by the American Diabetes Association and the American Podiatric Medical Association in January 2011 to summarize available evidence on the pathophysiology, natural history, presentations, and treatment recommendations for this entity. (J Am Podiatr Med Assoc 101(5): 437–446, 2011)