Detection, management, and prevention of diabetes-related foot disease in the Australian context.

Diabetes-related foot disease (DFD) is a widely feared complication among people who live with diabetes. In Australia and globally, rates of disability, cardio-vascular disease, lower extremity amputation, and mortality are significantly increased in patients with DFD. In order to understand and prevent these outcomes, we analyse the common pathogenetic processes of neuropathy, arterial disease, and infection. The review then summarises important management considerations through the interdisciplinary lens. Using Australian and international guidelines, we offer a stepwise, evidence-based practical approach to the care of patients with DFD.

Neutrophil specific granule and NETosis defects in gray platelet syndrome.

Gray platelet syndrome (GPS) is an autosomal recessive bleeding disorder characterized by a lack of α-granules in platelets and progressive myelofibrosis. Rare loss-of-function variants in neurobeachin-like 2 (NBEAL2), a member of the family of beige and Chédiak-Higashi (BEACH) genes, are causal of GPS. It is suggested that BEACH domain containing proteins are involved in fusion, fission, and trafficking of vesicles and granules. Studies in knockout mice suggest that NBEAL2 may control the formation and retention of granules in neutrophils. We found that neutrophils obtained from the peripheral blood from 13 patients with GPS have a normal distribution of azurophilic granules but show a deficiency of specific granules (SGs), as confirmed by immunoelectron microscopy and mass spectrometry proteomics analyses. CD34+ hematopoietic stem cells (HSCs) from patients with GPS differentiated into mature neutrophils also lacked NBEAL2 expression but showed similar SG protein expression as control cells. This is indicative of normal granulopoiesis in GPS and identifies NBEAL2 as a potentially important regulator of granule release. Patient neutrophil functions, including production of reactive oxygen species, chemotaxis, and killing of bacteria and fungi, were intact. NETosis was absent in circulating GPS neutrophils. Lack of NETosis is suggested to be independent of NBEAL2 expression but associated with SG defects instead, as indicated by comparison with HSC-derived neutrophils. Since patients with GPS do not excessively suffer from infections, the consequence of the reduced SG content and lack of NETosis for innate immunity remains to be explored.

The effectiveness of felt padding for offloading diabetes-related foot ulcers, at baseline and after one week of wear.

AIM: Felt padding is used to offload diabetes-related foot ulceration although limited quality data exists to support its use. This study aimed to quantify pressure offloading from neuropathic plantar foot ulcers in a clinical setting, when felt padding is first applied and after wear. METHODS: This study used a within-subjects, repeated measures design. Data was collected in a high-risk foot service. Peak plantar pressures, contact area and contact time were measured in 15 diabetes subjects with 16 non-complicated plantar neuropathic foot ulcers, with: no felt padding, newly applied felt padding and felt padding after one week of wear. RESULTS: Statistically significant decreases in peak pressure of 49% and 32% were measured with newly applied felt padding (188.0kPa; p<0.001) and worn felt padding (248kPa; p=0.003) respectively, compared to no padding (367.2kPa). Worn felt offloaded 32% less pressure than new felt however this did not reach statistical significance (p=.069). Corresponding increases in contact area of 18% and 14% occurred with newly applied felt padding (156.9cm2; p<.001) and worn felt padding (150.6cm2; p=0.003) compared to no padding (132.5cm2). Contact time was constant across testing conditions. CONCLUSIONS: New felt padding offloaded on average half the pressure applied to sites of plantar neuropathic ulceration, which reduced to one third after wear. Increased contact area under the foot is a possible mechanism contributing to pressure reduction. Further studies are required to evaluate effectiveness of felt padding directly on ulcer healing.