Objectives Endothelial dysfunction is linked to insulin resistance, inflammatory activation and increased cardiovascular risk in diabetes mellitus; however the mechanisms remain incompletely understood. Recent studies have identified pro-inflammatory signaling of Wnt5a through JNK as a regulator of metabolic dysfunction with potential relevance to vascular function. We sought to gain evidence that increased activation of Wnt5a-JNK signaling contributes to impaired endothelial function in patients with diabetes mellitus. Approach We measured flow-mediated dilation of the brachial artery and characterized freshly isolated endothelial cells by protein expression, eNOS activation, and nitric oxide production in from 85 subjects with Type 2 diabetes mellitus (n=42) and age- and sex-matched non-diabetic controls (n=43) and in human aortic endothelial cells treated with Wnt5a. Results Endothelial cells from patients with diabetes displayed 1.3-fold higher Wnt5a levels (P=0.01) along with 1.4-fold higher JNK activation (P<0.01) without a difference in total JNK levels. Higher JNK activation was associated with lower flow-mediated dilation, consistent with endothelial dysfunction (r=0.53, P=0.02). Inhibition of Wnt5a and JNK signaling restored insulin and A23187-mediated eNOS activation and improved nitric oxide production in endothelial cells from patients with diabetes. In endothelial cells from non-diabetic controls, rWnt5a treatment inhibited eNOS activation replicating the diabetic endothelial phenotype. In HAECs, Wnt5a-induced impairment of eNOS activation and nitric oxide production was reversed by Wnt5a and JNK inhibition. Conclusions Our findings demonstrate that non-canonical Wnt5a signaling and JNK activity contributes to vascular insulin resistance and endothelial dysfunction and may represent a novel therapeutic opportunity to protect the vasculature in patients with diabetes.

Our study suggests that language discordance does not affect 30-day complication and readmission rates after infrainguinal bypass.

Background Posttranslational protein modification with O‐linked N ‐acetylglucosamine (O‐Glc NA c) is linked to high glucose levels in type 2 diabetes mellitus (T2 DM ) and may alter cellular function. We sought to elucidate the involvement of O‐Glc NA c modification in endothelial dysfunction in patients with T2 DM . Methods and Results Freshly isolated endothelial cells obtained by J‐wire biopsy from a forearm vein of patients with T2 DM (n=18) was compared with controls (n=10). Endothelial O‐Glc NA c levels were 1.8‐ford higher in T2 DM patients than in nondiabetic controls ( P =0.003). Higher endothelial O‐Glc NA c levels correlated with serum fasting blood glucose level ( r =0.433, P =0.024) and hemoglobin A 1c ( r =0.418, P =0.042). In endothelial cells from patients with T2 DM , normal glucose conditions (24 hours at 5 mmol/L) lowered O‐Glc NA c levels and restored insulin‐mediated activation of endothelial nitric oxide synthase, whereas high glucose conditions (30 mmol/L) maintained both O‐Glc NA c levels and impaired insulin action. Treatment of endothelial cells with Thiamet G, an O‐Glc NA case inhibitor, increased O‐Glc NA c levels and blunted the improvement of insulin‐mediated endothelial nitric oxide synthase phosphorylation by glucose normalization. Conclusions Taken together, our findings indicate a role for O‐Glc NA c modification in the dynamic, glucose‐induced impairment of endothelial nitric oxide synthase activation in endothelial cells from patients with T2 DM . O‐Glc NA c protein modification may be a treatment target for vascular dysfunction in T2 DM .

Objective The option to retrieve inferior vena cava (IVC) filters has resulted in an increase in the utilization of these devices as stopgap measures in patients with relative contraindications to anticoagulation. These retrievable IVC filters, however, are often not retrieved and become permanent. Recent data from our institution confirmed a historically low retrieval rate. Therefore, we hypothesized that the implementation of a new IVC filter retrieval protocol would increase the retrieval rate of appropriate IVC filters at our institution. Methods All consecutive patients who underwent an IVC filter placement at our institution between September 2003 and July 2012 were retrospectively reviewed. In August 2012, a multidisciplinary task force was established, and a new IVC filter retrieval protocol was implemented. Prospective data were collected using a centralized interdepartmental IVC filter registry for all consecutive patients who underwent an IVC filter placement between August 2012 and September 2014. Patients were chronologically categorized into preimplementation (PRE) and postimplementation (POST) groups. Comparisons of outcome measures, including the retrieval rate of IVC filters along with rates of retrieval attempt and technical failure, were made between the two groups. Results In the PRE and POST groups, a total of 720 and 74 retrievable IVC filters were implanted, respectively. In the POST group, 40 of 74 filters (54%) were successfully retrieved compared with 82 of 720 filters (11%) in the PRE group (P < .001). Furthermore, a greater number of IVC filter retrievals were attempted in the POST group than in the PRE group (66% vs 14%; P < .001). No significant difference was observed between the PRE and POST groups for technical failure (17% vs 18%; P = .9). Conclusions The retrieval rate of retrievable IVC filters at our institution was significantly increased with the implementation of a new IVC filter retrieval protocol with a multidisciplinary team approach. This improved retrieval rate is possible with minimal dedication of resources and can potentially lead to a decrease in IVC filter-related complications in the future.

Objective: The modified Allen test (MAT) is an accepted but controversial way to evaluate palmar arch patency. There is a current lack of consensus in the literature regarding the reliability of the MAT. We hypothesized that the MAT is an inaccurate tool in determining the patency of a patient's palmar arch.Methods: We completed a prospective study at a single universityaffiliated institution. All patients presenting to the operating room or to the vascular surgery clinic for an arteriovenous fistula were enrolled beginning in June 2015. For each patient, a surgical resident in the third year of training or higher performed a physical examination including a MAT on both upper extremities. In-clinic palmar arch duplex ultrasound (US) was then performed by Registered Physician in Vascular Interpretation-certified vascular surgeons who were blinded to the results of the MAT. Univariate analysis was performed to evaluate the utility of the MAT.Results: There were 32 patients enrolled and 59 arms evaluated. Five arms were excluded because of indeterminate US findings or patient factors that limited an adequate physical examination. The MAT was positive for an incomplete arch in 14 (24%) arms, whereas US instead identified 23 (39%) incomplete arches. Of all 59 examinations performed, there were 5 (8.4%) false positives and 14 (24%) false negatives resulting in 19 (32%) discordant examinations (P ¼ .03; Table ). The sensitivity of the MAT was 39% (95% confidence interval [CI], 20%-61%), the specificity was 86% (95% CI, 70%-95%), the positive predictive value was 64% (95% CI, 36%-86%), and the negative predictive value was 69% (95% CI, 53%-81%). The accuracy of the MAT was 68% (95% CI, 37%-98%).Conclusions: The MAT is inaccurate and lacks sensitivity and is thus a poor tool for assessing palmar arch patency. We recommend that palmar arch duplex US be used as the primary diagnostic tool for evaluating the collateral circulation of the hand, especially before procedures that may compromise radial artery blood flow.