Diane Ochs

Guidelines for the treatment of venous ulcers

1. Co-chaired this panel2. University of South Florida, Tampa, FL3. Healthpoint Ltd., Fort Worth, TX4. University of California, San Francisco, CA5. University of Texas Medical Branch, Galveston, TX6. University of Cardiff, Cardiff, Wales, UK7. University of Pennsylvania, Philadelphia, PA8. Private practice, Warren, PA9. Private practice, Tamarac, FL10. University of Pittsburgh, Pittsburgh, PA11. St. Louis University, St. Louis, MO, and12. Washington University, St. Louis, MO

Sequential Cytokine Therapy for Pressure Ulcers: Clinical and Mechanistic Response

OBJECTIVE To compare the healing response of sequential topically applied cytokines to that of each cytokine alone and to a placebo in pressure ulcers, and to evaluate the molecular and cellular responses. SUMMARY BACKGROUND DATA Because of a deficiency of cytokine growth factors in chronic wounds and the reversal of impaired healing in animal models, pressure ulcer trials have been performed with several exogenously applied growth factors. Because single-factor therapy has not been uniformly successful, combination or sequential cytokine therapy has been proposed. Laboratory data have suggested that sequential treatment with granulocyte-macrophage/colony-stimulating factor (GM-CSF)/basic fibroblast growth factor (bFGF) might augment the previously reported effect of bFGF alone. METHODS A masked, randomized pressure ulcer trial was performed comparing sequential GM-CSF/bFGF therapy with that of each cytokine alone and with placebo during a 35-day period. The primary measure was wound volume decrease over time. Cytokine wound levels and mRNA levels were serially determined. Fibroblast-populated collagen lattices (FPCLs) were constructed from serial fibroblast biopsies. Cellular ultrastructure was evaluated by electron microscopy. Changes in ease of surgical closure and its relative cost were determined. RESULTS Ulcers treated with cytokines had greater closure than those in placebo-treated patients. Patients treated with bFGF alone did the best, followed by the GM-CSF/bFGF group. Patients treated with GM-CSF or bFGF had higher levels of their respective cytokine after treatment. Patients with the greatest amount of healing showed higher levels of platelet-derived growth factor (PDGF) on day 10 and transforming growth factor beta (TGFbeta1) on day 36. Message for the bFGF gene was upregulated after treatment with exogenous bFGF, suggesting autoinduction of the cytokine. FPCLs did not mimic the wound responses. Ultrastructure of wound biopsies showed response to bFGF. Treatment with any of the cytokines improved the wound by allowing easier wound closure. This was most marked for the bFGF-alone treatment, with a cost savings of

Long-term outcome study of growth factor-treated pressure ulcers

9,000 to

Decreasing amputation rates in patients with diabetes mellitus. An outcome study.

9,200. CONCLUSIONS Treatment with bFGF resulted in significantly greater healing than the other treatments in this trial. The clinical response appeared to be related to upregulation of the bFGF message and to increased levels of PDGF-AB, bFGF, and TGFbeta1 in the wounds and changes in ultrastructure. The resultant improvements could be correlated with cost savings.

Guidelines for the prevention of venous ulcers

BACKGROUND Exogenous application of growth factors have been reported in an attempt to accelerate healing of chronic wounds. Most of the trials were of brief duration with short to no follow-up periods. Long-term outcome studies are sparse for pressure ulcer therapies with success rates around 30% for both operative and nonoperative treatments. METHODS Follow-up evaluations were performed serially up to 12 months for patients completing a 35 day blinded, placebo-controlled cytokine clinical trial of pressure ulcers. RESULTS Fifty-four of 61 patients completed the follow-up period with 68.5% of the patients (37 of 54) being healed after 1 year. Of patients healing > or =85% during the active treatment phase, 84.6% were healed after 1 year compared with 61% of those that healed <85% during treatment (P <0.05). CONCLUSION Long-term outcome was better in this growth factor trial than with surgical or standard nonoperative treatment of pressure ulcers. Since only patients receiving exogenously applied cytokines achieved >85% closure during the treatment phase of the trial, the excellent long-term outcome appears attributable to the cytokine therapy.

A prospective, non comparative, multicenter study to investigate the effect of cadexomer iodine on bioburden load and other wound characteristics in diabetic foot ulcers

The lower-extremity amputation rate in people with diabetes mellitus is high, and the wound failure rate at the time of amputation is as high as 28%. Even with successful healing of the primary amputation site, amputation of part of the contralateral limb occurs in 50% of patients within 2 to 5 years. The purpose of this study was to provide valid outcome data before (control period) and 18 months after (test period) implementation of a multidisciplinary team approach using verified methods to improve the institutional care of wounds. Retrospective medical chart review was performed for 118 control patients and 116 test patients. The amputation rate was significantly decreased during the test period, and the amputations that were required were at a significantly more distal level. No above-the-knee amputations were required in 45 patients during the test period, compared with 14 of 76 patients during the control period. These outcome data suggest that unified care is an effective approach for the patient with diabetic foot problems.

A Prospective, Randomized Clinical Trial to Assess the Cost-effectiveness of a Modern Foam Dressing versus a Traditional Saline Gauze Dressing in the Treatment of Stage II Pressure Ulcers

1. Co-chaired this panel,2. University of South Florida, Tampa, Florida,3. Healthpoint Ltd., Fort Worth, Texas,4. Sinai Hospital, Baltimore, Maryland,5. University of Cardiff, Cardiff, Wales, UK,6. University of Pennsylvania, Philadelphia, Pennsylvania,7. Bay Pines VAMC, Bay Pines, Florida,8. Gannon University, Erie, Pennsylvania,9. University Hospital, Tamarac, Florida,10. University of Pittsburgh, Pittsburgh, Pennsylvania,11. St. Louis University, St. Louis, Missouri, and12. Washington University, Barnes Jewish Hospital, St. Louis, Missouri

An exploratory study of dermal replacement therapy in the treatment of stage III pressure ulcers

Few studies regarding wound treatment with topical antimicrobials evaluate change in the bacterial bioburden of the wound with treatment. This study sought out to determine the in vivo effect of cadexomer iodine antibacterial dressing on diabetic foot ulcers (DFUs) that were infected or achieved a critical level of colonisation, looking specifically at wound progression in relation to bioburden. Fifteen patients corresponding to 16 total DFUs met criteria of displaying clinical signs of infection or critical colonisation and were suitable for a topical antibacterial dressing. They underwent weekly treatment for 6 weeks. Cultures were taken at week 0, 3 and 6 as appropriate. At week 6 median log10 bacterial count reduction of 1.0 was observed from baseline (p = 0·025). At week 3‐ a median log10 bacterial count reduction of 0.3 was observed from baseline (p = 0·049). Over the study period there was a 53.6% median reduction of the wound surface area. There were no patients that completely healed their ulcer over the 6 week study period. There was a statistically significant median reduction in the bacterial load over the 6 week period (p = 0·025) as well as 3 weeks (p = 0·049). This was accompanied by a median reduction of 53.6% in ulcer surface area and 50% in ulcer depth from baseline to final.