LAFA is a useful adjunct for intra-operative stump perfusion assessment and can predict areas of poor stump healing and eschar formation. Diabetic patients seem to be at higher risk of stump eschar formation.
Fenofibrate, a proliferator-activated receptor (PPAR)α agonist, is the only oral medication demonstrated to prevent lower extremity amputations in diabetic patients. Phosphatidylcholines, generated by choline-ethanolamine phosphotransferase 1 (CEPT1) via the Kennedy Pathway, also induce PPARα activation, but their metabolism is altered in the setting of diabetes. It is unknown whether CEPT1 is essential for fenofibrate-mediated endothelial cell (EC) function. To evaluate this, we generated a murine model for conditional knockdown of
Cept1
in the endothelium (
Cept1EC
KO). Heart ECs (MHECs) were harvested from 6wk old
Cept1EC
KO and wildtype (WT) littermates, and cultured
in vitro
on growth factor-reduced Matrigel. Cultures were then supplemented with VEGF (50ng/mL), bFGF (50ng/mL), and fenofibrate (25uM), then assessed longitudinally at 0, 4, and 6 hours. We observed that compared to WT,
Cept1EC
KO MHECs had significantly less tubule formation (p < 0.0001). VEGF and bFGF failed to rescue
Cept1EC
KO MHECs, but demonstrated a robust agonist response in WT MHECs (bFGF: p=0.003; VEGF: p=0.0002). Interestingly, fenofibrate demonstrated complete rescue of
Cept1EC
KO MHECs at 4 and 6 hours of culture. This finding demonstrates that fenofibrate restores EC function even in the setting of impaired phospholipid biosynthesis. This observation may partially explain how fenofibrate confers added benefits in subjects with diabetic and peripheral arterial disease. Future work will further elucidate this mechanism of action in diabetic subjects.
and three patients had a major limb amputation. No major adverse events occurred in group 2. Thirty-day patency rate was 100% in the hybrid group and 88% in the endovascular group. During a follow-up of 12 months, primary patency rate was 66.7% (log-rank, 1.38; P ¼ not significant) in the endovascular group and 80% in the hybrid group.Conclusions: Hybrid-based iliac and femoral revascularization provides a minimally invasive approach to occlusive disease comparable with surgical bypasses and seems to have a better outcome when compared with endovascular treatment alone. Moreover, in group 1, the rate of additional intervention was lower and patency and limb salvage rates were higher in comparison with those achieved in group 2.
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