Best-practice algorithms for the use of a bilayered living cell therapy (Apligraf®) in the treatment of lower-extremity ulcers

Tissue-engineered skin substitutes such as Apligraf have emerged over the past 20 years as among the most carefully studied and efficacious of the advanced wound modalities. These products have been proven as effective enhancements to general wound care, promoting wound closure particularly in instances where conventional wound care fails. Marketed for hard-to-heal wounds since 1998, Apligraf has become part of standard wound care in many wound centers across the United States. Despite this situation, few general wound care guidelines incorporate advanced and active wound-healing technologies, such as tissue-engineered skin products. Because of this deficiency, appropriate patient selection and proper use of these product remain largely unaddressed within the general wound care community. Here, we describe the development of guidelines surrounding optimal use of the bilayered living cell therapy, Apligraf, in the treatment of the two types of lower extremity ulcers for which the product is FDA approved: venous leg ulcer and diabetic foot ulcer. The guidelines detailed in this article focus on the identification and selection of patients who are at risk for failure of standard wound care therapy and thus appropriate for Apligraf treatment. The intended audience for these guidelines is the general wound care practitioner, for whom the developed treatment algorithms and accompanying figure legends should provide practical, user-friendly direction simplifying both patient selection and appropriate use of Apligraf within the context of good wound-healing practice.     

Pericapillary fibrin cuffs in venous ulceration. Persistence with treatment and during ulcer healing.

A recent hypothesis suggests that venous hypertension leads to ulceration through the formation of pericapillary fibrin cuffs, which are presumed to impede the exchange of oxygen and other nutrients. In this report, we evaluated by direct immunofluorescence the presence of pericapillary fibrin at the edge of venous ulcers during the course of treatment with elastic compression. In an initial group of 23 patients studied at baseline, pericapillary fibrin cuffs were detected in 20 (91%) of 22 patients. The intensity of fibrin staining, rated blindly on a scale of 0 to 3, could not be correlated with several baseline parameters, including the clinical presence and extent of lipodermatosclerosis, ulcer size, venous recovery time, and transcutaneous oxygen measurements (TcPO2) taken next to the ulcer. Eleven of this initial group of 23 patients were randomly selected to receive elastic compression treatment, and were evaluated for the persistence of pericapillary fibrin at 60 and 120 days. Although a reduction (mean +/- SD = 50.2% +/- 25.7) in ulcer size occurred in 10 of the 11 patients, pericapillary fibrin was still present at the ulcer edge and with undiminished intensity. We conclude that pericapillary fibrin cuffs in venous ulcers persist with compression treatment and in spite of healing, and are unlikely to be directly related to the development of ulceration.     

Use of Cyclooxygenase Inhibitors and Risk of Melanoma in High-Risk Patients

Background Results from in vitro and animal studies suggest that cyclooxygenase (COX) inhibitors may reduce the risk of melanoma, but among humans, the evidence remains limited.
Objective In a pilot retrospective cohort, to determine the relationship between the use of COX inhibitors and the incidence, recurrence, and metastases of melanoma in high-risk patients.
Methods Reviewing computerized records at the Miami Veterans Affairs Medical Center, we retrospectively examined the association between COX inhibitor use and melanoma incidence, recurrence, and metastases in high-risk subjects: white subjects previously diagnosed with melanoma (1996–2003). We evaluated three potential outcomes: new melanoma diagnosis, recurrence of a previous melanoma, and melanoma metastasis.
Results Eighty-three subjects with melanoma were included. There was one metastasis among 28 subjects prescribed COX inhibitors, whereas four new melanomas (7.3%), two melanoma recurrences, and six metastases (10.9%) occurred among 55 patients not prescribed COX inhibitors. Although no individual outcomes measures reached statistical significance, combining the three measures, these were significantly lower in users of COX inhibitors compared with nonusers (1 vs 12;  p = .05  ). After adjustment for age and tumor depth of invasion, COX inhibitor users had significantly lower rates of melanoma outcome measures (odds ratio 0.08; 95% confidence interval 0.01–0.77;  p = .03  ).
Conclusion Potential exists for chemoprevention of melanoma among high-risk patients.