OBJECTIVE -We studied the relationships of diabetic ulcer wound fluid matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and transforming growth factor-ß1 (TGF-ß1) with wound healing rate.RESEARCH DESIGN AND METHODS -The ulcers were cleansed to remove exudates, and wound fluids were collected for analysis of MMP-2 and -9, TIMP-1, and TGF-ß1.RESULTS -At presentation, MMP-9 and the MMP-9 -to-TIMP-1 ratio correlated inversely with the wound healing rate at 28 days (P Ͻ 0.001). MMP-9 and the MMP-9 -to-TIMP-1 ratio were lower in the 23 patients who achieved complete healing at 12 weeks versus the 39 who did not. The pro-MMP-9 concentration was predictive of healing within 12 weeks. Addition of cutoffs for TIMP-1 (Ͼ480 pg/ml) and TGF-ß (Ͼ115 pg/ml) further improved its predictive power (area under the curve 0.94).CONCLUSIONS -These findings suggest that a milieu with high MMP-9 may be indicative of inflammation and poor wound healing. Measurements of MMP-9, TIMP-1, and TGF-ß in wound fluid may help to identify ulcers at risk of poor healing.

Topical propolis is a well-tolerated therapy for wound healing and this pilot in human DFU indicates for the first time that it may enhance wound closure in this setting when applied weekly. A multi-site randomized controlled of topical propolis now appears to be warranted in diabetic foot ulcers.

Background Pressure offloading treatment is critical for healing diabetes-related foot ulcers (DFU). Yet the 2011 Australian DFU guidelines regarding offloading treatment are outdated. A national expert panel aimed to develop a new Australian guideline on offloading treatment for people with DFU by adapting international guidelines that have been assessed as suitable to adapt to the Australian context. Methods National Health and Medical Research Council procedures were used to adapt suitable International Working Group on the Diabetic Foot (IWGDF) guidelines to the Australian context. We systematically screened, assessed and judged all IWGDF offloading recommendations using best practice ADAPTE and GRADE frameworks to decide which recommendations should be adopted, adapted or excluded in the Australian context. For each recommendation, we re-evaluated the wording, quality of evidence, strength of recommendation, and provided rationale, justifications and implementation considerations, including for geographically remote and Aboriginal and Torres Strait Islander peoples. This guideline, along with five accompanying Australian DFU guidelines, underwent public consultation, further revision and approval by ten national peak bodies (professional organisations). Results Of the 13 original IWGDF offloading treatment recommendations, we adopted four and adapted nine. The main reasons for adapting the IWGDF recommendations included differences in quality of evidence ratings and clarification of the intervention(s) and control treatment(s) in the recommendations for the Australian context. For Australians with plantar DFU, we recommend a step-down offloading treatment approach based on their contraindications and tolerance. We strongly recommend non-removable knee-high offloading devices as first-line treatment, removable knee-high offloading devices as second-line, removable ankle-high offloading devices third-line, and medical grade footwear as last-line. We recommend considering using felted foam in combination with the chosen offloading device or footwear to further reduce plantar pressure. If offloading device options fail to heal a person with plantar DFU, we recommend considering various surgical offloading procedures. For people with non-plantar DFU, depending on the type and location of the DFU, we recommend using a removable offloading device, felted foam, toe spacers or orthoses, or medical grade footwear. The six new guidelines and the full protocol can be found at: https://diabetesfeetaustralia.org/new-guidelines/. Conclusions We have developed a new Australian evidence-based guideline on offloading treatment for people with DFU that has been endorsed by ten key national peak bodies. Health professionals implementing these offloading recommendations in Australia should produce better DFU healing outcomes for their patients, communities, and country.

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