Background Resolvins are lipid mediators generated by leukocytes during the resolution phase of inflammation. They have been shown to regulate the transition from inflammation to tissue repair; however, it is unknown whether resolvins play a role in tissue revascularization following ischemia. Methods We used a murine model of hind limb ischemia (HLI), coupled with laser Doppler perfusion imaging, micro computed tomography (microCT) and targeted mass spectrometry, to assess the role of resolvins in revascularization and inflammation-resolution. Results In mice undergoing HLI, we identified resolvin D2 (RvD2) in bone marrow and skeletal muscle by mass spectrometry (n=4-7 per group). We also identified RvD2 in skeletal muscle biopsies from humans with peripheral artery disease. Monocytes were recruited to skeletal muscle during HLI and isolated monocytes produced RvD2 in a lipoxygenase-dependent manner. Exogenous RvD2 enhanced perfusion recovery in HLI and microCT of limb vasculature revealed greater volume, with evidence of tortuous arterioles indicative of arteriogenesis (n=6-8 per group). Unlike other treatment strategies for therapeutic revascularization that exacerbate inflammation, RvD2 did not increase vascular permeability, but reduced neutrophil accumulation and the plasma levels of TNF-α and GM-CSF. In mice treated with RvD2, histopathological analysis of skeletal muscle of ischemic limbs showed more regenerating myocytes with centrally located nuclei. RvD2 enhanced endothelial cell migration in a Rac-dependent manner, via its receptor, GPR18, and Gpr18-deficient mice had an endogenous defect in perfusion recovery following HLI. Importantly, RvD2 rescued defective revascularization in diabetic mice. Conclusions RvD2 stimulates arteriogenic revascularization during HLI suggesting that resolvins may be a novel class of mediators that both resolve inflammation and promote arteriogenesis.

Background: Insufficient data exist for peristomal pyoderma gangrenosum (PPG), which primarily affects patients with inflammatory bowel disease (IBD). Aims:To evaluate the risk factors and treatment response of PPG in IBD patients in a real-life cohort.Methods: Cases of PPG were identified retrospectively using ICD-9/10 codes in patients with IBD who had an ostomy at a tertiary care centre. Disease-specific characteristics were compared between groups with and without PPG, and response to therapy was evaluated in patients with PPG. Results:The cohort included 41 IBD patients with PPG and 123 IBD controls with an ostomy who never developed PPG. Patients with PPG were more likely to be female (76% vs 51%, P = 0.006), had higher BMIs (29.78 ± 0.89 vs 23.53 ± 0.51, P < 0.0001) and had increased usage of pouch belts (97% vs 71%, P = 0.0008) compared to controls. There were no differences in age at surgery (41.76 ± 2.60 vs 43.49 ± 1.50, P = 0.57) or IBD diagnosis (63% vs 54% Crohn's disease, P = 0.28) between PPG and controls. 85% of PPG patients achieved complete resolution with different treatments, including surgery. Complete resolution with topical corticosteroids and calcineurin inhibitors alone were low (14% and 13% respectively). Higher rates of complete resolution were reported with anti-tumour necrosis factor (TNF) agents (63%) and surgical interventions (80%). Conclusions:Female gender, higher BMI and pouch belts were associated with increased risk of developing PPG. Most PPG cases resolved after treatment with the highest rates of complete resolution seen with anti-TNF agents and surgical intervention.

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