We conclude after 5 years of follow-up of this randomized controlled trial that a bypass with saphenous vein has better patency rates at all intervals and needs fewer reoperations. Saphenous vein should be the graft material of choice for above-knee femoropopliteal bypasses and should not be preserved for reinterventions. Polytetrafluoroethylene is an acceptable alternative if the saphenous vein is not available.

Objective— The immune system is thought to play a crucial role in regulating collateral circulation (arteriogenesis), a vital compensatory mechanism in patients with arterial obstructive disease. Here, we studied the role of lymphocytes in a murine model of hindlimb ischemia. Methods and Results— Lymphocytes, detected with markers for NK1.1, CD3, and CD4, invaded the collateral vessel wall. Arteriogenesis was impaired in C57BL/6 mice depleted for Natural Killer (NK)-cells by anti-NK1.1 antibodies and in NK-cell–deficient transgenic mice. Arteriogenesis was, however, unaffected in Jα281-knockout mice that lack NK1.1 + Natural Killer T (NKT)-cells, indicating that NK-cells, rather than NKT-cells, are involved in arteriogenesis. Furthermore, arteriogenesis was impaired in C57BL/6 mice depleted for CD4 + T-lymphocytes by anti-CD4 antibodies, and in major histocompatibility complex (MHC)-class-II–deficient mice that more selectively lack mature peripheral CD4 + T-lymphocytes. This impairment was even more profound in anti-NK1.1-treated MHC-class-II–deficient mice that lack both NK- and CD4 + T-lymphocytes. Finally, collateral growth was severely reduced in BALB/c as compared with C57BL/6 mice, 2 strains with different bias in immune responsiveness. Conclusions— These data show that both NK-cells and CD4 + T-cells modulate arteriogenesis. Promoting lymphocyte activation may represent a promising method to treat ischemic disease.

Objective-Because late vein graft failure is caused by intimal hyperplasia (IH) and accelerated atherosclerosis, and these processes are thought to be inflammation driven, influx of monocytes is one of the first phenomena seen in IH, we would like to provide direct evidence for a role of the MCP-1 pathway in the development of vein graft disease.

Genetic factors appear to be important in the restenotic process after percutaneous coronary intervention (PCI), as well as in inflammation, a pivotal factor in restenosis. TNFalpha, a key regulator of inflammatory responses, may exert critical influence on the development of restenosis after PCI. The GENetic DEterminants of Restenosis (GENDER) project included 3104 patients who underwent a successful PCI. Systematic genotyping for six polymorphisms in the TNFalpha gene was performed. The role of TNFalpha in restenosis was also assessed in ApoE*3-Leiden mice, TNFalpha knockout mice, and by local delivery of a TNFalpha biosynthesis inhibitor, thalidomide. The -238G-1031T haplotype of the TNFalpha gene increased clinical and angiographic risk of restenosis (P=0.02 and P=0.002, respectively). In a mouse model of reactive stenosis, arterial TNFalpha mRNA was significantly time-dependently up-regulated. Mice lacking TNFalpha or treated locally with thalidomide showed a reduction in reactive stenosis (P=0.01 and P=0.005, respectively). Clinical and preclinical data indicate that TNFalpha plays an important role in restenosis. Therefore, TNFalpha genotype may be used as a risk marker for restenosis and may contribute to individual patient screening prior to PCI in clinical practice. Inhibition of TNFalpha may be an anti-restenotic target strategy.

Indeterminate thyroid cytology (Bethesda III and IV) corresponds to follicular-patterned benign and malignant lesions, which are particularly difficult to differentiate on cytology alone. As ~25% of these nodules harbor malignancy, diagnostic hemithyroidectomy is still custom. However, advanced preoperative diagnostics are rapidly evolving.This review provides an overview of additional molecular and imaging diagnostics for indeterminate thyroid nodules in a preoperative clinical setting, including considerations regarding cost-effectiveness, availability, and feasibility of combining techniques. Addressed diagnostics include gene mutation analysis, microRNA, immunocytochemistry, ultrasonography, elastosonography, computed tomography, sestamibi scintigraphy, [18F]-2-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET), and diffusion-weighted magnetic resonance imaging.The best rule-out tests for malignancy were the Afirma® gene expression classifier and FDG-PET. The most accurate rule-in test was sole BRAF mutation analysis. No diagnostic had both near-perfect sensitivity and specificity, and estimated cost-effectiveness. Molecular techniques are rapidly advancing. However, given the currently available techniques, a multimodality stepwise approach likely offers the most accurate diagnosis, sequentially applying one sensitive rule-out test and one specific rule-in test. Geographical variations in cytology (e.g., Hürthle cell neoplasms) and tumor genetics strongly influence local test performance and clinical utility. Multidisciplinary collaboration and implementation studies can aid the local decision for one or more eligible diagnostics.

These data provide evidence that complement factor C5a-induced mast cell activation is highly involved in vein graft disease, which identifies new targets to prevent vein graft disease.

Inhibition of intraplaque haemorrhage by controlling neovessels maturation holds promise to improve plaque stability.

Background Identification of diseased and normal parathyroid glands during parathyroid surgery can be challenging. The aim of this study was to assess whether near-infrared (NIR) fluorescence imaging using administration of a low-dose Methylene Blue (MB) at the start of surgery could provide optical guidance during parathyroid surgery and assist in the detection of parathyroid adenomas. Methods Patients diagnosed with primary hyperparathyroidism planned for parathyroid resection were included. Patients received 0.5 mg/kg MB intravenously directly after start of anesthesia. During surgery, NIR fluorescence imaging was performed to identify parathyroid adenomas. Imaging results were compared to a previous published feasibility study in which 12 patients received MB after surgical identification of the adenoma. Results 13 patients were included in the current study. In 10/12 patients with a histologically proven adenoma, the adenoma was fluorescent. Mean Signal to Background Ratio (SBR) was 3.1 ± 2.8. Mean diameter of the resected lesions was 17 ± 9 mm (range 5 – 28 mm). Adenomas could be identified up to 145 minutes after administration, which was the longest timespan until resection. Interestingly, in 3 patients, a total of 6 normal parathyroid glands (median diameter 2.5 mm) with a SBR of 1.8 ± 0.4 were identified using NIR fluorescence imaging. Conclusion Early administration of low dose MB provided guidance during parathyroid surgery by identifying both parathyroid adenomas and normal parathyroid glands. In patients where difficult identification of the parathyroid adenoma is expected, or when normal glands have to be identified, administration of MB could improve surgical outcome.