It is unlikely that a threshold AVVQ score could be used to aid referral of patients with C2 disease. The distribution of veins (unilateral vs. bilateral) must be adjusted for when reporting AVVQ scores.

Extracorporeal Shock Wave Therapy (ESWT) is used clinically in various disorders including chronic wounds for its pro-angiogenic, proliferative, and anti-inflammatory effects. However, the underlying cellular and molecular mechanisms driving therapeutic effects are not well characterized. Macrophages play a key role in all aspects of healing and their dysfunction results in failure to resolve chronic wounds. We investigated the role of ESWT on macrophage activity in chronic wound punch biopsies from patients with non-healing venous ulcers prior to, and two weeks post-ESWT, and in macrophage cultures treated with clinical shockwave intensities (150–500 impulses, 5 Hz, 0.1 mJ/mm2). Using wound area measurements and histological/immunohistochemical analysis of wound biopsies, we show ESWT enhanced healing of chronic ulcers associated with improved wound angiogenesis (CD31 staining), significantly decreased CD68-positive macrophages per biopsy area and generally increased macrophage activation. Shockwave treatment of macrophages in culture significantly boosted uptake of apoptotic cells, healing-associated cytokine and growth factor gene expressions and modulated macrophage morphology suggestive of macrophage activation, all of which contribute to wound resolution. Macrophage ERK activity was enhanced, suggesting one mechanotransduction pathway driving events. Collectively, these in vitro and in vivo findings reveal shockwaves as important regulators of macrophage functions linked with wound healing. This immunomodulation represents an underappreciated role of clinically applied shockwaves, which could be exploited for other macrophage-mediated disorders.

The global prevalence of adults with diabetes is currently in excess of 415 million and is expected to increase to over 640 million by 2040. 1 Foot ulceration is common in patients with diabetes, with a 25% estimated lifetime risk of developing a foot ulcer. 2 Diabetic foot ulceration (DFU) is associated with significant morbidity, including major limb amputation and cardiovascular events, as well as mortality. 2,3 It is difficult to treat and often necessitates

The novel finding of this study is that SDMA levels were predictive of all cause-mortality and correlated with disease severity. Further studies should assess the role of nitric oxide donors in patients with high levels of SDMA.

The Aberdeen Varicose Vein Questionnaire (AVVQ) is validated and frequently used as a patient-reported disease-specific quality of life (QoL) outcome in trials of varicose veins. The AVVQ comprises a manikin diagram where patients draw their varicose veins and 12 questions including pain, skin changes, use of support stockings, appearance and impact. AVVQ scores range from 0 to 100 (worst possible QoL), with the manikin diagram contributing up to 22 points, depending on the extent of the varicose veins.Our experience of using the AVVQ in the NIHR HTA funded CLASS trial comparing varicose vein treatments suggested that (i) a proportion of patients fail to complete the manikin diagram; (ii) scoring the manikin diagram was time-consuming and (iii) it was not possible to directly capture AVVQ responses from participants electronically (there was a need for a paper questionnaire). We therefore investigated the potential to use the AVVQ without the manikin diagram.Using retrospective data from CLASS, we correlated the AVVQ (scored with and without the manikin diagram) against two clinical measures of disease severity. Individuals with more severe disease had higher AVVQ scores (regardless of whether the manikin diagram component was included or not).In a prospective study of test-retest reliability involving 32 patients with varicose veins, we demonstrated good level of agreement between paired diagrams. In the same study, there was high level of agreement between two independent scorers.Our results suggest that the AVVQ could be used without the manikin diagram, which could result in cost/time savings for trials.