Wyatt G. Payne

Comparison of Negative Pressure Wound Therapy Using Vacuum-Assisted Closure With Advanced Moist Wound Therapy in the Treatment of Diabetic Foot Ulcers A multicenter randomized controlled trial

OBJECTIVE—The purpose of this study was to evaluate safety and clinical efficacy of negative pressure wound therapy (NPWT) compared with advanced moist wound therapy (AMWT) to treat foot ulcers in diabetic patients. RESEARCH DESIGN AND METHODS—This multicenter randomized controlled trial enrolled 342 patients with a mean age of 58 years; 79% were male. Complete ulcer closure was defined as skin closure (100% reepithelization) without drainage or dressing requirements. Patients were randomly assigned to either NPWT (vacuum-assisted closure) or AMWT (predominately hydrogels and alginates) and received standard off-loading therapy as needed. The trial evaluated treatment until day 112 or ulcer closure by any means. Patients whose wounds achieved ulcer closure were followed at 3 and 9 months. Each study visit included closure assessment by wound examination and tracings. RESULTS—A greater proportion of foot ulcers achieved complete ulcer closure with NPWT (73 of 169, 43.2%) than with AMWT (48 of 166, 28.9%) within the 112-day active treatment phase (P = 0.007). The Kaplan-Meier median estimate for 100% ulcer closure was 96 days (95% CI 75.0–114.0) for NPWT and not determinable for AMWT (P = 0.001). NPWT patients experienced significantly (P = 0.035) fewer secondary amputations. The proportion of home care therapy days to total therapy days for NPWT was 9,471 of 10,579 (89.5%) and 12,210 of 12,810 (95.3%) for AMWT. In assessing safety, no significant difference between the groups was observed in treatment-related complications such as infection, cellulitis, and osteomyelitis at 6 months. CONCLUSIONS—NPWT appears to be as safe as and more efficacious than AMWT for the treatment of diabetic foot ulcers.

Comparative evaluation of silver-containing antimicrobial dressings and drugs

Wound dressings containing silver as antimicrobial agents are available in various forms and formulations; however, little is understood concerning their comparative efficacy as antimicrobial agents. Eight commercially available silver‐containing dressings, Acticoat® 7, Acticoat® Moisture Control, Acticoat® Absorbent, Silvercel™, Aquacel® Ag, Contreet® F, Urgotol® SSD and Actisorb®, were tested to determine their comparative antimicrobial effectiveness in vitro and compared against three commercially available topical antimicrobial creams, a non treatment control, and a topical silver‐containing antimicrobial gel, Silvasorb®. Zone of inhibition and quantitative testing was performed by standard methods using Escherichia coli, Pseudomonas aeruginosa, Streptococcus faecalis and Staphylococcus aureus. Results showed all silver dressings and topical antimicrobials displayed antimicrobial activity. Silver‐containing dressings with the highest concentrations of silver exhibited the strongest bacterial inhibitive properties. Concreet® F and the Acticoat® dressings tended to have greater antimicrobial activity than did the others. Topical antimicrobial creams, including silver sulfadiazine, Sulfamylon and gentamicin sulfate, and the topical antimicrobial gel Silvasorb® exhibited superior bacterial inhibition and bactericidal properties, essentially eliminating all bacterial growth at 24 hours. Silver‐containing dressings are likely to provide a barrier to and treatment for infection; however, their bactericidal and bacteriostatic properties are inferior to commonly used topical antimicrobial agents.

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

Maintenance of wound bacterial balance

9,000 to

Guidelines to aid healing of acute wounds by decreasing impediments of healing

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.

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

BACKGROUND There is a critical number of bacteria above which tissue responds with infection. This balance of 10(5) or fewer bacteria/g tissue is also required for wound healing to proceed normally. This study evaluated whether a chronic wound once in bacterial balance can maintain that balance over time. METHODS Serial biopsies for bacterial analyses were obtained weekly during a blinded, placebo-controlled cytokine clinical trial of pressure ulcers. To enter the trial ulcers had to be debrided and have a bacterial count of 10(5) or fewer bacteria/g tissue with no beta-hemolytic streptococci. RESULTS In all, 96% of cultures (350/363) remained at <10(2) bacteria/g tissue over the 5-week trial; 3% had 10(2) to 10(5), and only 1% had >10(5) bacteria/g tissue. CONCLUSION Chronic pressure ulcers, once debrided and brought into bacterial balance, will remain in bacterial balance if cared for and kept free of necrotic tissue.

Cultured pressure ulcer fibroblasts show replicative senescence with elevated production of plasmin, plasminogen activator inhibitor-1, and transforming growth factor-β1

1. Co-chaired this panel, 2. Department of Surgery, University of Michigan, Ann Arbor, Michigan, 3. Department of Surgery, University of South Florida, Tampa, Florida, 4. Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, 5. Department of Surgery, Sinai Hospital/Johns Hopkins University, Baltimore, Maryland, 6. Department of Surgery, NYU School of Medicine, New York, New York, 7. PolyRemedy Inc., Mountain View, California, 8. Department of Wound Healing, Cardiff University, Cardiff, Wales, United Kingdom, 9. Department of Surgery, Johns Hopkins University, Baltimore, Maryland, 10. Institute for Tissue Regeneration, Repair, and Rehabilitation, Bay Pines VA Healthcare System, Bay Pines, Florida, 11. Division of Plastic Surgery, University of South Florida, Tampa, Florida, 12. Department of Surgery, University of Arizona, Tucson, Arizona, and 13. Barnes Jewish Hospital, Washington University, St. Louis, Missouri

Obesity and Surgical Wound Healing: A Current Review

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.

Formulated collagen gel accelerates healing rate immediately after application in patients with diabetic neuropathic foot ulcers

In a 16‐patient study, cultured fibroblast populations from normal skin were able to replicate an average of 14.8 ± 2.2 times before becoming senescent, while fibroblast populations from the ulcer bed reached the end of their replicative life span after 7.2 ± 1.9 population doublings (p= 0.001). Fibroblast populations from 10 of 16 pressure ulcers became senescent after fewer than five population doublings, whereas when populations of fibroblasts from adjacent normal skin were studied, only 2 of 16 became senescent within this same time period. In addition, only an occasional fibroblast from normal skin stained positively for senescence‐associated β‐galactosidase compared to approximately 50% of equally aged ulcer bed fibroblasts (p = 0.0060). Senescent ulcer bed fibroblasts secreted significantly more plasmin than early passage ulcer bed fibroblasts (p= 0.0237), nearly six times as much plasmin as early passage normal skin fibroblasts (p < 0.0001), three and a half times the level of normal skin fibroblasts of the same age (11.52 ± 4.58 µg/mg protein; p= 0.0003), and more than one and a half times the level of senescent normal skin fibroblasts (p= 0.0525). Senescent pressure ulcer fibroblasts generated significantly more plasminogen activator inhibitor‐1 (1179.27 ± 25.37 ng/mg protein) than normal skin fibroblasts of the same age (132.16 ± 16.20 ng/mg protein; p = 0.0357). Also, senescent ulcer bed fibroblasts produced higher levels of transforming growth factor‐β1, but these were not significantly different from senescent normal skin fibroblasts. Although senescent ulcer fibroblasts produce elevated levels of plasminogen activator inhibitor‐1 and transforming growth factor‐β1, the ratio of these factors to plasmin levels suggests that this may have little influence on extracellular matrix synthesis or maintenance in the chronic wound. These data show that cultured fibroblasts from most patient pressure ulcers profile a wound environment that is associated with an increasing population of senescent fibroblasts; however, factors within the chronic wound environment that promote cellular senescence remain unclear. We have proposed that a prolonged inflammatory response may be a contributing factor to the chronic wound condition.

Wound-healing trajectories as outcome measures of venous stasis ulcer treatment.

Objective. The correlation between obesity and deficient wound healing has long been established. This review examines the current literature on the mechanisms involved in obesity-related perioperative morbidity. Methods. A literature search was performed using Medline, PubMed, Cochrane Library, and Internet searches. Keywords used include obesity, wound healing, adipose healing, and bariatric and surgical complications. Results. Substantial evidence exists demonstrating that obesity is associated with a number of postoperative complications. Specifically in relation to wound healing, explanations include inherent anatomic features of adipose tissue, vascular insufficiencies, cellular and composition modifications, oxidative stress, alterations in immune mediators, and nutritional deficiencies. Most recently, advances made in the field of gene array have allowed researchers to determine a few plausible alterations and deficiencies in obese individuals that contribute to their increased risk of morbidity and mortality, especially wound complications. Conclusion. While the literature discusses how obesity may negatively affect health on various of medical fronts, there is yet to be a comprehensive study detailing all the mechanisms involved in obesity-related morbidities in their entirety. Improved knowledge and understanding of obesity-induced physiological, cellular, molecular, and chemical changes will facilitate better assessments of surgical risks and outcomes and create efficient treatment protocols for improved patient care of the obese patient population.