US-National Institutes of Health-funded research for cutaneous wounds in 2012.

Chronic cutaneous wounds are a major burden on patients, healthcare providers, and the US healthcare system. This study, carried out in part by the Wound Healing Society's Government Regulatory Committee, aimed to evaluate the current state of National Institutes of Health funding of cutaneous wound healing-related research projects. National Institutes of Health Research Portfolio Online Reporting Tools Expenditures & Results system was used to identify wound healing projects funded by the National Institutes of Health in the 2012 fiscal year. Research projects focusing on cutaneous wound prevention/education, mechanisms, complications, treatment, or imaging/monitoring were included in the analysis. Ninety-one projects were identified, totaling a collective funding of $29,798,991 and median funding of $308,941. Thirteen institutes/centers from the National Institutes of Health were responsible for awarding funds; three of which (National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases) accounted for 60.4% of the grant funding. The predominant funding mechanisms included R01 (48.3%), R43 (14.3%), and R21 (9.9%). New applications and pre-existing applications accounted for 39.6 and 55.0% of the awarded grants, respectively. Grants awarded to investigators affiliated with universities accounted for 68.1% of grants and 25.3% were to investigators in the private sector. This analysis of current National Institutes of Health funding may facilitate more transparency of National Institutes of Health-allocated research funds and serve as an impetus to procure additional support for the field of wound healing.

Topical and biologic therapies for diabetic foot ulcers.

Chronic DFUs are a growing global health concern due to the implied high rates of morbidity and mortality. Standard-of-care modalities sometimes are not sufficient for some recalcitrant ulcers. The use of adjuvant topical therapies including advanced dressings and biologic therapies should be considered in patients whose DFU did not reduce in size after receiving standard care for a period of 4 weeks. These advanced treatments must be used in combination with standard care measures, including debridement, moist wound healing, offloading, and infection control.

Evidence-based management of common chronic lower extremity ulcers.

Chronic lower extremity ulcers are a significant burden on patients and health care systems worldwide. Although relatively common, these wounds can be difficult to treat and present a challenge to physicians. Treatment has often been based on anecdotal accounts; however, there is a growing emphasis on using evidence-based conclusions to guide clinical decisions. In this review article, the standard of care and adjuvant therapies of venous leg ulcers and diabetic foot ulcers are presented from an evidence-based perspective.

Giant ulcerating squamous cell carcinoma arising from linear porokeratosis: a case study.

Linear porokeratosis is one of the infrequent variants of porokeratosis, a rare disorder of keratinization that may develop into several epidermal malignancies, among them squamous cell carcinoma. Clinical surveillance for malignancy is imperative, but in cases when large or many lesions are present, surgical removal of porokeratosis lesions would result in an unfavorable amount of scarring. A case of a large, nonhealing full-thickness ulcer caused by a giant ulcerating squamous cell carcinoma occurring within lesions of long-standing linear porokeratosis is reported in a 43-year-old woman with a recent diagnosis of ulcerative colitis (UC). Wide excision of the ulcer and plastic surgical reconstruction of the area were performed. PET scans did not show metastases, so her prognosis is good based on definitive excision of the tumor. Physicians should be aware of this cutaneous disease and the importance of annual follow-up for these patients to monitor for any lesion that exhibits clinical features concerning for malignancy.

Diabetic foot ulcers: evaluation and management.

Diabetic foot ulcers (DFUs) are a common complication of diabetes and present a significant health risk to patients, as well as impose a large economic burden. Evaluation for contributory factors that may impact general health or healing, such as hyperglycemia, peripheral artery disease, neuropathy, and nutritional status, is of the utmost importance. Management of DFUs requires involvement of a multidisciplinary team and a standardized approach to patient care. Standard therapy for DFUs includes offloading and debridement. Assessment and control of infection are critical, including determining the severity of the infection, which may drive therapeutic approaches. For recalcitrant ulcers, adjuvant therapies are used to hasten the healing process, and newer therapies are under investigation.

The FDA and designing clinical trials for chronic cutaneous ulcers.

Treatment of chronic wounds can present a challenge, with many patients remaining refractory to available advanced therapies. As such, there is a strong need for the development of new products. Unfortunately, despite this demand, few new wound-related drugs have been approved over the past decade. This is in part due to unsuccessful clinical trials and subsequent lack of Food and Drug Administration (FDA) approval. In this article, we discuss the FDA approval process, how it relates to chronic wound trials, common issues that arise, and how best to manage them. Additionally, problems encountered specific to diabetic foot ulcers (DFU) and venous leg ulcers (VLU) are addressed. Careful construction of a clinical trial is necessary in order to achieve the best possible efficacy outcomes and thereby, gain FDA approval. How to design an optimal trial is outlined.

A prospective pilot study of ultrasound therapy effectiveness in refractory venous leg ulcers.

Venous insufficiency is the most common cause of leg ulcers in the United States. Venous leg ulcers cost the health care system billions of dollars annually, and healing rates are less than 70% with standard of care; therefore, new therapies are needed to increase healing times and minimize associated costs. Non contact ultrasound therapy has been used to treat a variety of chronic wounds including venous leg ulcers, and it is thought that ultrasound has an effect on decreasing the bacterial count in wounds, although the exact mechanism of action of ultrasound is yet to be determined. We conducted an open labelled pilot study of 10 refractory venous ulcers of large size to determine the effect of non contact ultrasound on wound closure, bacterial counts, expression of inflammatory cytokines and pain reduction. We lacked a sham control group but we compared the baseline and end of treatment assessments and noted the differences. We found a significant reduction in wound area (P = 0·0039) over the 4-week treatment period. We also found a decline in individual and total bacterial counts; however, these differences were not significant. For all patients, there was also a trend toward reduced inflammatory cytokine expression compared with baseline levels; however, this reduction did not reach statistical significance. Interestingly, there was a correlation between healing and change in cytokine expression, which showed statistically significance for tumour necrosis factor (TNF)-αP = 0·0395, IL-1a P = 0·0351, IL-6 P = 0·0508, IL-8 P = 0·0990. Pain as measured by the visual analogue scale (VAS) was reduced from 4 at the baseline to 2·7 by the end of the study. In conclusion, we found that patients treated with ultrasound therapy and compression therapy show clinical improvement over the course of 4 weeks and had a decrease in inflammatory cytokines, bacterial counts and pain.

Update on Keloid Management: Clinical and Basic Science Advances.

BACKGROUND: Keloids are benign, fibroproliferative lesions that represent abnormal healing resulting in excessive fibrosis. They are composed of mainly type III (early) or type I (late) collagen. Some of the symptoms include pruritus, tenderness, and pain. Often, they are very difficult to treat and prevent from recurrence. In contrast to hypertrophic scars, keloids extend beyond the margin of the wound. THE PROBLEM: There is very limited evidence on the best wound management for minimizing scarring. Multiple available therapeutic modalities have been used for the treatment of keloids; however, high-recurrence rates continue to be reported. Unsuccessful treatment of keloids leads to psychological impact on the patients and increased economic burden. BASIC/CLINICAL SCIENCE ADVANCES: Currently, there are biological and antineoplastic agents that can potentially treat and prevent excessive scar formation. Some of them have been used as "off label" therapies, and others are still in the experimental phase such as interferon alpha (IFN-α), imiquimod, and transforming growth factor beta1 (TGF-ß1). The use of IFN-α2b showed 18% recurrence rate when applied to postsurgical excised keloids. Imiquimod 5% can lower recurrence rate on postshaved keloids to 37.5% at 6-month and to 0% at a 12-month follow-up period. TGF-ß1 oligonucleotides have shown effective and long-lasting inhibition of TGF-ß-mediated scarring in vitro as well as in animal models. Daily injections of neutralizing antibodies against TGF-ß1 and -ß2 have shown successful reductions in scarring. CONCLUSION: Latest discoveries in the use of novel agents suggest therapeutic alternatives for the prevention of recurrences of hypertrophic scars and postexcision keloid lesions.

Refractory erythromelalgia of the ears: response to mexiletine.

Erythromelalgia is a rare condition characterized by burning pain, erythema, swelling, and increased temperature usually in the extremities. We present an unusual presentation of erythromelalgia of the ears in a patient who has been refractory to multiple therapies and in whom relief of symptoms was achieved with the use of mexiletine. A review of clinical presentation, pathophysiology, and therapeutic options are presented.