Case studies evaluating transdermal continuous oxygen for the treatment of chronic sickle cell ulcers.

OBJECTIVE: Refractory leg ulcerations are common in homozygous sickle cell anemia. In this case series, patients were treated with transdermal continuous oxygen therapy (TCOT), based on the hypothesis that oxygen deprivation caused by arteriovenous shunting may be remedied by providing oxygen directly to the wound bed. The authors believe this is the first attempt to treat sickle cell ulcers with TCOT. CASE PRESENTATION: Five patients with long histories of recurring sickle cell disease ulcers that would not heal with various conventional and/or other adjunctive wound healing modalities were treated with TCOT. The patients had recurring nonhealing wounds for 30, 21, 20, 20, and 15 years, respectively. All 5 patients healed or showed substantial improvement in the treatment periods of 3 to 36 weeks. CONCLUSION: The authors conclude that TCOT may be a novel, effective, and inexpensive modality in treating patients with sickle cell disease ulcers. Improvement was typically noticeable within 2 weeks. Further clinical trials may be considered to evaluate the efficacy of TCOT in sickle cell ulcers.

A retrospective cohort study evaluating efficacy in high-risk patients with chronic lower extremity ulcers treated with negative pressure wound therapy.

The purpose of this study was to evaluate the efficacy of negative pressure wound therapy (NPWT) compared with standard of care on wound healing in high-risk patients with multiple significant comorbidities and chronic lower extremity ulcers (LEUs) across the continuum of care settings. A retrospective cohort study of 'real-world' high-risk patients was conducted using Boston University Medical Center electronic medical records, along with chart abstraction to capture detailed medical history, comorbidities, healing outcomes and ulcer characteristics. A total of 342 patients, 171 NPWT patients with LEUs were matched with 171 non-NPWT patients with respect to age and gender, were included in this cohort from 2002 to 2010. The hazard ratios (HRs) were estimated by COX proportional hazard models after adjusting for potential confounders. The NPWT patients were 2·63 times (95% CI = 1·87-3·70) more likely to achieve wound closure compared with non-NPWT patients. Moreover, incidence of wound closure in NPWT patients were increased in diabetic ulcers (HR = 3·26, 95% CI = 2·21-4·83), arterial ulcers (HR = 2·27, CI = 1·56-3·78) and venous ulcers (HR = 6·31, 95% CI = 1·49-26·6) compared with non-NPWT patients. In addition, wound healing appeared to be positively affected by the timing of NPWT application. Compared with later NPWT users (1 year or later after ulcer onset), early NPWT users (within 3 months after ulcer onset) and intermediate NPWT users (4-12 months after ulcer onset) were 3·38 and 2·18 times more likely to achieve wound healing, respectively. This study showed that despite the greater significant comorbidities, patients receiving NPWT healed faster. Early use of NPWT demonstrated better healing. The longer the interval before intervention is with NPWT, the higher the correlation is with poor outcome.

A pilot study evaluating non-contact low-frequency ultrasound and underlying molecular mechanism on diabetic foot ulcers.

Non-contact low-frequency ultrasound (NCLF-US) devices have been increasingly used for the treatment of chronic non-healing wounds. The appropriate dose for NCLF-US is still in debate. The aims of this pilot study were to evaluate the relationship between dose and duration of treatment for subjects with non-healing diabetic foot ulcers (DFUs) and to explore the correlation between wound healing and change of cytokine/proteinase/growth factor profile. This was a prospective randomised clinical study designed to evaluate subjects with non-healing DFUs for 5 weeks receiving standard of care and/or NCLF-US treatment. Subjects were randomly assigned to one of the three groups: application of NCLF-US thrice per week (Group 1), NCLF-US once per week (Group 2) and the control (Group 3) that received no NCLF-US. All subjects received standard wound care plus offloading for a total of 4 weeks. Percent area reduction (PAR) of each wound compared with baseline was evaluated weekly. Profiles of cytokines/proteinase/growth factors in wound fluid and biopsied tissue were quantified to explore the correlation between wound healing and cytokines/growth factor expression. Twelve DFU patients, 2 (16·7%) type 1 and 10 (83·3%) type 2 diabetics, with an average age of 58 ± 10 years and a total of 12 foot ulcers were enrolled. Average ulcer duration was 36·44 ± 24·78 weeks and the average ABI was 0·91 ± 0·06. Group 1 showed significant wound area reduction at weeks 3, 4 and 5 compared with baseline, with the greatest PAR, 86% (P < 0·05); Groups 2 and 3 showed 25% PAR and 39% PAR, respectively, but there were no statistically significant differences between Groups 2 and 3 over time. Biochemical and histological analyses indicated a trend towards reduction of pro-inflammatory cytokines (IL-6, IL-8, IL-1ß, TNF-α and GM-CSF), matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF) and macrophages in response to NCLF-US consistent with wound reduction, when compared with control group subjects. This proof-of-concept pilot study demonstrates that NCLF-US is effective in treating neuropathic diabetic foot ulcers through, at least in part, inhibiting pro-inflammatory cytokines in chronic wound and improving tissue regeneration. Therapeutic application of NFLU, thrice (3) per week, renders the best wound area reduction.

A prospective, randomized clinical study evaluating the effect of transdermal continuous oxygen therapy on biological processes and foot ulcer healing in persons with diabetes mellitus.

Hypoxia is a major factor in delayed wound healing. The aim of this prospective, randomized, clinical trial was to compare outcomes of treatment in persons with chronic diabetic foot ulcers (DFUs) randomly assigned to transdermal continuous oxygen therapy (TCOT) for 4 weeks as an adjunct to standard care (debridement, offloading, and moisture). Nine patients (age 58.6±7.1, range 38-73 years) received TCOT (treatment group) and eight patients (age 59.9±12.6, range 35-76 years) received standard care alone (control group). Most patients (12) were male, and all had a Wagner I or II foot ulcer for an average of 14 (control group) or 20 months (treatment group). Weekly wound measurements and wound tissue biopsies were obtained and wound fluid collected. Levels of pro-inflammatory cytokines and proteases in wound fluid samples were analyzed using Luminex-based multiplex assays. Tissue-resident macrophages were quantified by immunohistochemistry. At week 4, average wound size reduction was 87% (range 55.7% to 100%) in the treatment group compared to 46% (15% to 99%) in the control group (P <0.05). Changes in cytokine levels (IL-6, IL-8) and proteinases (MMP-1,-2,-9, TIMP-1) at weeks 2 to 4 in wound fluid correlated with clinical findings. CD68+ macrophage counts showed statistically significant reduction in response to TCOT compared to the control group (P <0.01). The results of this study show that TCOT may facilitate healing of DFUs by reversing the inflammatory process through reduction in pro-inflammatory cytokines and tissue-degrading proteases. Additional research to elucidate the effects of this treatment on complete healing and increase understanding about the role of wound fluid analysis is needed.

Updating on understanding and managing chronic wound.

The art of healing wounds is quite complex. It requires the patient's local condition in conjunction with their systemic condition to provide the most ideal wound environment. As wound care is expanding with advances in technology, we are facing a variety of different wound care products based on an assortment of bioengineered skin substances, growth factors, oxygen therapies, low frequency ultrasound and even low energy light. While these emerging evidence-based treatments prove to be promising in improving clinical outcomes and quality of life, it challenges providers to provide cost-effective treatment plans. The goal of this paper is to introduce a discussion regarding practical clinical application of various forms of advanced wound technologies in order to optimize the art of wound healing.