Continuous diffusion of oxygen improves diabetic foot ulcer healing when compared with a placebo control: a randomised, double-blind, multicentre study.

OBJECTIVE: The aim of this study was to assess whether continuous diffusion of oxygen improves healing in people receiving treatment for diabetic foot ulcers (DFU). METHOD: A double-blind, placebo control randomised study to receive either active continuous diffusion of oxygen (CDO) therapy using an active CDO device, or a fully operational placebo device without delivering oxygen. Patients were followed until closure or 12 weeks. Patients, caretakers, treating physicians and independent evaluators were blinded to the study arm. All patients received identical offloading, debridement, dressings and follow-up. RESULTS: We enrolled 146 people with DFUs (77% male, aged 56.3±12.4 years). A significantly higher proportion (195%) of DFUs healed in the CDO arm compared with placebo (32.4% versus 16.7%, p=0.033). The time to 50% DFU closure was significantly shorter in patients that received CDO therapy (mean 18.4 versus 28.9 days, p=0.001). There were no differences in overall adverse events (p=0.66) or ulcer-related adverse events (p=0.30) in the active and placebo treatment groups. The relative performance of active CDO over placebo became greater when used in larger wounds (273%), in more chronic wounds (334%) and in weight bearing wounds (465%). CONCLUSION: The results of this study demonstrate that CDO leads to higher proportion of healed DFUs (p=0.033) and a faster time to closure compared with placebo in people with DFUs (p=0.015). Relative performance did not vary significantly with wound size (p=0.80), but revealed better relative performance in more chronic wounds (p=0.008) and in weight-bearing wounds (p=0.003).

Molecular Biomarkers of Oxygen Therapy in Patients with Diabetic Foot Ulcers.

Hyperbaric oxygen therapy (HBOT) and topical oxygen therapy (TOT) including continuous diffuse oxygen therapy (CDOT) are often utilized to enhance wound healing in patients with diabetic foot ulcerations. High pressure pure oxygen assists in the oxygenation of hypoxic wounds to increase perfusion. Although oxygen therapy provides wound healing benefits to some patients with diabetic foot ulcers, it is currently performed from clinical examination and imaging. Data suggest that oxygen therapy promotes wound healing via angiogenesis, the creation of new blood vessels. Molecular biomarkers relating to tissue inflammation, repair, and healing have been identified. Predictive biomarkers can be used to identify patients who will most likely benefit from this specialized treatment. In diabetic foot ulcerations, specifically, certain biomarkers have been linked to factors involving angiogenesis and inflammation, two crucial aspects of wound healing. In this review, the mechanism of how oxygen works in wound healing on a physiological basis, such as cell metabolism and growth factor signaling transduction is detailed. Additionally, observable clinical outcomes such as collagen formation, angiogenesis, respiratory burst and cell proliferation are described. The scientific evidence for the impact of oxygen on biomolecular pathways and its relationship to the outcomes in clinical research is discussed in this narrative review.

Does Debridement Improve Clinical Outcomes in People With Diabetic Foot Ulcers Treated With Continuous Diffusion of Oxygen?

OBJECTIVE: This post hoc analysis evaluates the association between the frequency of diabetic foot ulcer (DFU) debridement and the proportion of ulcers treated with active continuous diffusion of oxygen (CDO) that heal in a 12-week evaluation period. MATERIALS AND METHODS: There were 146 patients with DFUs (77% men; average age, 56.3 ± 12.4 years) enrolled in a double-blind, placebo-controlled, randomized study to receive either active CDO or an otherwise fully operational placebo device. Patients were followed for 12 weeks or until wound closure. All patients received identical offloading, dressings, and follow-up. Ulcer debridement was left to the discretion of the treating physician and recorded from physician self-report as a dichotomous variable. RESULTS: A significantly higher proportion (204%) of ulcers healed in the CDO group compared with the placebo (46.2% vs. 22.6%, respectively; P = .016). The relative performance of active CDO over placebo became greater when frequent debridement was used (51.2% vs. 21.3%, respectively; P = .006). CONCLUSIONS: A significantly greater percentage of healing was recorded in patients receiving active CDO therapy than those receiving a placebo device in addition to standard wound care with identical dressings, debridement recommendations, and offloading. The relative performance of CDO appears to increase with the use of frequent debridement.

A Prospective, Randomized, Double-Blind Multicenter Study Comparing Continuous Diffusion of Oxygen Therapy to Sham Therapy in the Treatment of Diabetic Foot Ulcers.

BACKGROUND: Over the past generation, preclinical data have suggested that there is a potential physiologic benefit to applying oxygen topically to wounds. However, we are unaware of any studies in the literature that have robustly assessed whether this would lead to a higher proportion of healing in similarly treated people without oxygen. Therefore, the purpose of this study was to assess this in people being treated for chronic diabetic foot ulcers (DFUs). METHODS: We enrolled and randomized 100 subjects with DFUs (79% male, aged 58.3 ± 12.1 years) to receive either active continuous diffusion of oxygen (CDO) therapy using an active CDO device, or an otherwise fully operational sham device that provided moist wound therapy (MWT) without delivering oxygen. Patients were followed until closure or 12 weeks, whichever was sooner. Patients, treating physicians and independent evaluators were blinded to the study arm. All patients received identical offloading, dressings and follow-up. RESULTS: There were no significant differences in assessed descriptive characteristics between the treatment arms ( P > .05 for all). A significantly higher proportion of people healed in the active arm compared to sham (46% vs 22%, P = .02). This relative effect became greater in more chronic wounds (42.5% vs 13.5%, P = .006). Patients randomized to the active device experienced significantly faster rates of closure relative to the sham ( P < .001). CONCLUSIONS: The results of this study suggest that continuously diffused oxygen over a wound leads to significantly higher rates of closure, and faster time to closure, compared to similarly treated patients receiving standard therapy coupled with a sham device. Furthermore, the relative efficacy appears to improve the more the therapy may be needed (more chronic and larger wounds).

Correlation of cartilage stiffness to thickness and level of degeneration using a handheld indentation probe.

The in vivo assessment of the quality of cartilage is a critical tool to determine how to clinically treat damaged cartilage. Utilizing nondestructive indentation, a hand-held instrument (ACTAEON Probe) was used to rapidly measure the stiffness of articular cartilage, which can then be correlated to cartilage condition. An integrated series of tests were performed to determine whether the Probe is sensitive enough to detect early degenerative changes in articular cartilage and to examine if it is dependent on the thickness of the cartilage being tested. Results demonstrated that there is no effect of thickness on the Probe measurements for clinically relevant human cartilage samples, that the Probe is sensitive enough to detect different levels of cartilage degeneration, and that Probe data correlate well with traditional creep indentation testing. This study demonstrates the utility of the Probe for detecting degenerative changes in animal and human joints.