• Patients with carotid artery stenosis have higher levels of serum cFAS, and patients with diabetes have even higher levels of serum cFAS activity compared to patients with no diabetes. • Serum cFAS activity correlates with serum glucose and predominantly in LDL cholesterol fractions in patients with carotid artery stenosis. • In LDL cholesterol, cFAS immunoprecipitates with ApoB. • Patients with high serum cFAS also have high carotid plaque FAS and saturated fatty acids. • cFAS appears to originate from the liver as mice with selective knockdown of FAS in the liver tissue have the lowest serum cFAS levels.
OBJECTIVE Despite persisting questions regarding its appropriateness, 30-day readmission is an increasingly common quality metric used to influence hospital compensation in the United States. However, there is currently insufficient evidence to identify which patients are at highest risk for readmission after aneurysmal subarachnoid hemorrhage (SAH). The objective of this study was to identify predictors of 30-day readmission after SAH, to focus preventative efforts, and to provide guidance to funding agencies seeking to risk-adjust comparisons among hospitals. METHODS The authors performed a case-control study of 30-day readmission among aneurysmal SAH patients treated at a single center between 2003 and 2013. To control for geographic distance from the hospital and year of treatment, the authors randomly matched each case (30-day readmission) with approximately 2 SAH controls (no readmission) based on home ZIP code and treatment year. They evaluated variables related to patient demographics, socioeconomic characteristics, comorbidities, presentation severity (e.g., Hunt and Hess grade), and clinical course (e.g., need for gastrostomy or tracheostomy, length of stay). Conditional logistic regression was used to identify significant predictors, accounting for the matched design of the study. RESULTS Among 82 SAH patients with unplanned 30-day readmission, the authors matched 78 patients with 153 nonreadmitted controls. Age, demographics, and socioeconomic factors were not associated with readmission. In univariate analysis, multiple variables were significantly associated with readmission, including Hunt and Hess grade (OR 3.0 for Grade IV/V vs I/II), need for gastrostomy placement (OR 2.0), length of hospital stay (OR 1.03 per day), discharge disposition (OR 3.2 for skilled nursing vs other disposition), and Charlson Comorbidity Index (OR 2.3 for score ≥ 2 vs 0). However, the only significant predictor in the multivariate analysis was discharge to a skilled nursing facility (OR 3.2), and the final model was sensitive to criteria used to enter and retain variables. Furthermore, despite the significant association between discharge disposition and readmission, less than 25% of readmitted patients were discharged to a skilled nursing facility. CONCLUSIONS Although discharge disposition remained significant in multivariate analysis, most routinely collected variables appeared to be weak independent predictors of 30-day readmission after SAH. Consequently, hospitals interested in decreasing readmission rates may consider multifaceted, cost-efficient interventions that can be broadly applied to most if not all SAH patients.
De novo phospholipogenesis, mediated by choline-ethanolamine phosphotransferase 1 (CEPT1), is essential for phospholipid activation of transcription factors such as peroxisome proliferator–activated receptor α (PPARα) in the liver. Fenofibrate, a PPARα agonist and lipid-lowering agent, decreases amputation incidence in patients with diabetes. Because we previously observed that CEPT1 is elevated in carotid plaque of patients with diabetes, we evaluated the role of CEPT1 in peripheral arteries and PPARα phosphorylation (Ser12). CEPT1 was found to be elevated in diseased lower-extremity arterial intima of individuals with peripheral arterial disease and diabetes. To evaluate the role of Cept1 in the endothelium, we engineered a conditional endothelial cell (EC)–specific deletion of Cept1 via induced VE-cadherin-CreERT2–mediated recombination (Cept1Lp/LpCre+). Cept1Lp/LpCre+ ECs demonstrated decreased proliferation, migration, and tubule formation, and Cept1Lp/LpCre+ mice had reduced perfusion and angiogenesis in ischemic hind limbs. Peripheral ischemic recovery and PPARα signaling were further compromised by streptozotocin-induced diabetes and ameliorated by feeding fenofibrate. Cept1 endoribonuclease-prepared siRNA decreased PPARα phosphorylation in ECs, which was rescued with fenofibrate but not PC16:0/18:1. Unlike Cept1Lp/LpCre+ mice, Cept1Lp/LpCre+Ppara−/− mice did not demonstrate hind-paw perfusion recovery after feeding fenofibrate. Therefore, we demonstrate that CEPT1 is essential for EC function and tissue recovery after ischemia and that fenofibrate rescues CEPT1-mediated activation of PPARα.
Background This study aimed to determine the impact of preoperative exposure to intravenous contrast for CT and the risk of developing postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. Methods This prospective, multicentre cohort study included adults undergoing gastrointestinal resection, stoma reversal or liver resection. Both elective and emergency procedures were included. Preoperative exposure to intravenous contrast was defined as exposure to contrast administered for the purposes of CT up to 7 days before surgery. The primary endpoint was the rate of AKI within 7 days. Propensity score‐matched models were adjusted for patient, disease and operative variables. In a sensitivity analysis, a propensity score‐matched model explored the association between preoperative exposure to contrast and AKI in the first 48 h after surgery. Results A total of 5378 patients were included across 173 centres. Overall, 1249 patients (23·2 per cent) received intravenous contrast. The overall rate of AKI within 7 days of surgery was 13·4 per cent (718 of 5378). In the propensity score‐matched model, preoperative exposure to contrast was not associated with AKI within 7 days (odds ratio (OR) 0·95, 95 per cent c.i. 0·73 to 1·21; P = 0·669). The sensitivity analysis showed no association between preoperative contrast administration and AKI within 48 h after operation (OR 1·09, 0·84 to 1·41; P = 0·498). Conclusion There was no association between preoperative intravenous contrast administered for CT up to 7 days before surgery and postoperative AKI. Risk of contrast‐induced nephropathy should not be used as a reason to avoid contrast‐enhanced CT.
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