Multicenter, randomized controlled, observer-blinded study of a nitric oxide generating treatment in foot ulcers of patients with diabetes-ProNOx1 study.

The aim of this multicenter, prospective, observer-blinded, parallel group, randomized controlled trial was to assess the safety and efficacy of EDX110, a nitric oxide generating medical device, in the treatment of diabetic foot ulcers in a patient group reflecting "real world" clinical practice compared against optimal standard care. Participants were recruited from ten hospital sites in multidisciplinary foot ulcer clinics. The ulcers were full thickness, with an area of 25-2,500 mm2 and either a palpable pedal pulse or ankle brachial pressure index > 0.5. Infected ulcers were included. Treatment lasted 12 weeks, or until healed, with a 12-week follow-up period. Both arms were given optimal debridement, offloading and antimicrobial treatment, the only difference being the fixed used of EDX110 as the wound dressing in the EDX110 group. 135 participants were recruited with 148 ulcers (EDX110-75; Control-73), 30% of which were clinically infected at baseline. EDX110 achieved its primary endpoint by attaining a median Percentage Area Reduction of 88.6% compared to 46.9% for the control group (p = 0.016) at 12 weeks in the intention-to-treat population. There was no significant difference between wound size reduction achieved by EDX110 after 4 weeks and the wound size reduction achieved in the control group after 12 weeks. EDX110 was well tolerated. Thirty serious adverse events were reported (12 in the EDX110 group, of which 4 were related to the ulcer; 18 in the control group, of which 10 were related and 1 possibly related to the ulcer), with significant reduction in serious adverse events related to the ulcer in EDX group. There was no significant difference in adverse events. This study, in a real world clinical foot ulcer population, demonstrates the ability of EDX110 to improve healing, as measured by significantly reducing the ulcer area, compared to current best clinical practice.

Measuring Plantar Tissue Stress in People With Diabetic Peripheral Neuropathy: A Critical Concept in Diabetic Foot Management.

Excessive stress on plantar tissue over time is one of the leading causes of diabetic foot ulcers among people with diabetic peripheral neuropathy. Plantar tissue stress (PTS) is a concept that attempts to integrate several well-known mechanical factors into one measure, including plantar pressure, shear stress, daily weight-bearing activity, and time spent in prescribed offloading interventions (adherence). Despite international diabetic foot guidelines recommending the measure of each of these individual mechanical factors in people with neuropathy, only recently has technology enabled their combined measurement to determine PTS. In this article we review the concept of PTS, the mechanical factors involved, and the findings of pivotal articles reporting measures of PTS in people with neuropathy. We also discuss key existing gaps in this field, including the lack of standards to measure and report PTS, a lack of practical solutions to measure shear stress, and the lack of PTS thresholds that may indicate benefit or detriment to people with neuropathy. To address some of these gaps, we propose recommended clinical and research standards for measuring and reporting PTS in people with neuropathy. Last, we forecast future clinical, research, and technological advancements that may use PTS to highlight the importance of this critical concept in the prevention and management of diabetic foot ulcers.

Real time presence of a microbiologist in a multidisciplinary diabetes foot clinic.

Multidisciplinary foot-care teams (MDFT) are recommended in the management of severe diabetic foot disease [1]. However, even though infection is often the dominant immediate risk, it is rare to have real time input from a microbiologist. We highlight the value of a microbiologist as a MDFT member.