Primary stenting of the SFA and PA provides durable results in patients with TASC A and B lesions and may be an effective treatment strategy. This approach is significantly less effective when used in treating those with TASC C and D disease. Based on the results in this series, the use of primary stenting does not extend the anatomic limits of the current treatment recommendations for catheter-based intervention in patients with infrainguinal occlusive disease.
Lysine acetylation plays a critical role in cellular regulation and is implicated in human disease. Sirtuin deacetylases remove acetyl groups from modified lysine residues, and sirtuin 3 (SIRT3) has been identified as a target for cancer therapeutics. Robust and high-throughput screening methods for these targets will be important to the development of therapeutics. This article describes the use of self-assembled monolayer desorption/ionization mass spectrometry, or SAMDI-MS-a label-free drug discovery tool-to characterize SIRT3 activity and discover inhibitors. SAMDI-MS was used to analyze a peptide array having 361 distinct acetylated peptides to identify an active SIRT3 substrate (GYK Ac RGC). This peptide was used in a screen of 100,000 small molecules to identify inhibitors of SIRT3. A total of 306 SIRT3 inhibitors were identified, with one compound, SDX-437, having an IC 50 of 700 nM with >100-fold selectivity for SIRT3 over SIRT1.
The objective was to investigate the incidence of thromboembolic stroke in patients with chronic kidney disease (CKD) and atrial fibrillation (AF) treated with and without warfarin. We investigated the incidence of thromboembolic stroke and of major bleeding in 399 unselected patients with CKD and AF treated with warfarin to maintain an international normalized ratio (INR) between 2.0 and 3.0 (N = 232) and without warfarin (N = 167). Of the 399 patients, 93 (23%) were receiving hemodialysis, and 132 (33%) had an estimated glomerular filtration rate (GFR) of 15 mL/min/1.73 m 2 At the 31-month follow-up of patients treated with warfarin and 23-month follow-up of patients not treated with warfarin, thromboembolic stroke developed in 21 of 232 patients (9%) treated with warfarin and in 43 of 167 patients (26%) not treated with warfarin (P 0.001). Major bleeding occurred in 32 of 232 patients (14%) treated with warfarin and in 15 of 167 patients (9%) not treated with warfarin (P not significant). Stepwise Cox regression analysis showed that significant independent predictors of thromboembolic stroke were use of warfarin (odds ratio, 0.28; P 0.0001) and prior stroke or transient ischemic attack (odds ratio, 2.9; P 0.05). In conclusion, this observational study showed that CKD patients with AF treated with warfarin to maintain an INR between 2.0 and 3.0 had a significant reduction in thromboembolic stroke and an insignificant increase in major bleeding.
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