Short-Term and Long-Term Fluvastatin Inhibit Effects of Thrombospondin-1 on Human Vascular Smooth Muscle Cells.

INTRODUCTION: Vascular smooth muscle cells are important in intimal hyperplasia. Thrombospondin-1 is a matricellular protein involved in the vascular injury response. Statins are cholesterol lowering drugs that have beneficial cardiovascular effects. Statis have been shown to inhibit smooth muscle migration through the mevalonate pathway. This effect is thought to be mediated by small G protein Ras and Rho turnover which requires many hours. While many patients undergoing treatment for vascular disease are on statins, many are not. Thus immediate pretreatment with statins before surgery may be beneficial. We hypothesized that statins have effects independent of the mevalonate pathway and thus have an immediate effect. METHODS: Human vascular smooth muscle cells were pretreated for 20 h (long-term) or 20 min (short-term) with fluvastatin, or mevalonolactone plus fluvastatin. Thrombospondin-1-induced migration, activation of p42/p44 extracellular signal-regulated kinase, c-Src, focal adhesion kinase and PI3 kinase was determined. The effect of fluvastatin on thrombospondin-1-induced expression of THBS1, FOS, HAS2 and TGFB2 was examined. RESULTS: Both treatments inhibited thrombospondin-1-induced chemotaxis back to the control group. Mevalonolactone reversed the long-term statin effect by increasing migration but had no effect on the short-term statin response. p42/p44 extracellular signal-regulated kinase was activated by thrombospondin-1 and both treatments augmented activation. Neither treatment affected c-Src activity, but both inhibited focal adhesion kinase and PI3 kinase activity. Only long-term statin treatment inhibited THBS1 expression while both treatments inhibited FOS and TGFB2 expression. Neither treatment affected HAS2. FOS knockdown inhibited thrombospondin-1-induced HAS2 but not TGFß2 gene expression. CONCLUSION: Long-term fluvastatin inhibited thrombospondin-1-induced chemotaxis through the mevalonate pathway while short-term fluvastatin inhibited chemotaxis through an alternate mechanism. Short-term stains have immediate effects independent of the mevalonate pathway. Acute local treatment with statins followed by longer term therapy may limit the vascular response to injury.

A Case of Bilateral Hearing Loss.

CASE PRESENTATION: A 53-year-old male presented to the emergency department with acute onset of bilateral hearing loss as well as vertigo and severe vomiting. The Head Impulse- Nystagmus-Test of Skew exam was indicative of a central neurologic process. Computed tomography angiogram of the head and neck revealed near-total bilateral vertebral artery occlusions in the second and third segments. The patient was admitted for further evaluation; subsequent magnetic resonance imaging revealed multiple areas of infarction in the cerebellar hemispheres, medulla, and occipital lobes. DISCUSSION: This case describes a unique presentation of a posterior stroke. Common symptoms include vertigo, loss of balance, and vomiting. However, bilateral hearing loss as a prominent symptom is uncommon. Imaging revealed a rare finding of bilateral vertebral artery occlusion.

Blood Culture Results and Overtreatment Associated With the Use of a 1-Hour Sepsis Bundle.

BACKGROUND: Some experts recommend using a 1-h sepsis bundle, but clinical data supporting this strategy are lacking. OBJECTIVES: We aimed to determine the rate of, and clinical predictors for, bacteremia for patients undergoing a 1-h sepsis bundle, and to determine the percentage of "code sepsis" patients who are ultimately diagnosed with sepsis or a bacterial infection. METHODS: This retrospective chart review evaluated code sepsis patients from three emergency departments (EDs) that utilize a 1-h sepsis bundle. The primary outcome was the rate of true-positive blood cultures. Secondarily, we analyzed various clinical factors using logistic regression analysis to determine which are associated with bacteremia. RESULTS: Of the 544 code sepsis patients analyzed, 33.8% (95% confidence interval [CI] 29.9-38.0%) were ultimately diagnosed with sepsis, and 54.6% (95% CI 50.3-58.8%) were diagnosed with a bacterial infection. Exactly 7.0% (95% CI 5.0-9.5%) of the blood cultures performed were true positives. On multivariate logistic regression analysis, temperature > 38°C (100.4°F) or < 36°C (96.8°F), lactate > 4 mmol/L, and indwelling line/device were found to be positively associated with true-positive blood cultures. CONCLUSION: In a group of code sepsis patients from facilities that use a 1-h sepsis bundle, the majority were ultimately not diagnosed with sepsis, and nearly half did not have a bacterial infection. A small minority of patients had bacteremia. Restricting blood culture ordering in patients with possible sepsis to only those who have increased risk for bacteremia could lead to a more judicious use of blood cultures.