The use of NSAIDs was associated with increased risk of major bleeding, stroke/SE, and hospitalization. The safety and efficacy of DE 150 and 110 mg b.i.d. relative to warfarin were not altered. (Randomized Evaluation of Long Term Anticoagulant Therapy [RE-LY]; NCT00262600).

P atients presenting with large ischemic strokes may develop uncontrollable, progressive brain edema that puts them at risk for compression of brain parenchyma and cerebral herniation. 23 There are a limited number of therapeutic options, but research has shown that operative procedures, such as decompressive hemicraniectomy (DH), decrease patient mortality.32 Malignant infarction treated only by conservative approaches results in a mortality rate of 80% within the 1st week of the stroke. 15Edema that does not respond to medical treatment necessitates DH as a life-saving procedure. Studies have demonstrated that DH surgery can result in a reduction of mortality rate to 30% and, if decompression is performed within 24 hours of stroke onset, to 10%. 7,12,18,24,32 While DH imabbreviatioNs BMI = body mass index; DH = decompressive hemicraniectomy; DVT = deep vein thrombosis; ICA = internal carotid artery; IVC = inferior vena cava; MCA = middle cerebral artery; MI = myocardial infarction; MLS = midline shift; mRS = modified Rankin Scale; NIHSS = National Institutes of Health Stroke Scale; tPA = tissue plasminogen activator. obJective Patients presenting with large-territory ischemic strokes may develop intractable cerebral edema that puts them at risk of death unless intervention is performed. The purpose of this study was to identify predictors of outcome for decompressive hemicraniectomy (DH) in ischemic stroke. methods The authors conducted a retrospective electronic medical record review of 1624 patients from 2006 to 2014. Subjects were screened for DH secondary to ischemic stroke involving the middle cerebral artery, internal carotid artery, or both. Ninety-five individuals were identified. Univariate and multivariate analyses were performed for an array of clinical variables in relationship to functional outcome according to the modified Rankin Scale (mRS). Clinical outcome was assessed at 90 days and at the latest follow-up (mean duration 16.5 months). results The mean mRS score at 90 days and at the latest follow-up post-DH was 4. Good functional outcome was observed in 40% of patients at 90 days and in 48% of patient at the latest follow-up. The mortality rate at 90 days was 18% and at the last follow-up 20%. Univariate analysis identified a greater likelihood of poor functional outcome (mRS scores of 4-6) in patients with a history of stroke .66]; p = 0.017), peak midline shift (MLS) > 10 mm ]; p = 0.011), or a history of myocardial infarction ]; p = 0.04). Multivariate analysis demonstrated elevated odds of poor functional outcome associated with a history of stroke .05]; p = 0.008), MLS > 10 mm ; p = 0.007), a history of diabetes .88]; p = 0.01), delayed time from onset of stroke to DH (OR 1.32 [95% CI 1.02-1.72]; p = 0.037), and evidence of pupillary dilation prior to DH .51]; p = 0.04). Patients with infarction involving the dominant hemisphere had higher odds of unfavorable functional outcome at 90 days ]; p = 0.014), but at the latest follow-up, cerebral dominance was not significantly related to outc...

Annualized rates of all outcomes were constant with better efficacy of D150, less major bleeding with D110, and low intracerebral haemorrhage rates for both doses. There were no additional safety concerns. This is the longest continuous randomized experience of a novel anticoagulant.

Scavenger receptor class B member 1 (SR-BI, also known as SCARB1) is the primary receptor for the selective uptake of cholesterol from high-density lipoprotein (HDL). SR-BI is present in several key tissues; however, its presence and function in the liver is deemed the most relevant for protection against atherosclerosis. Cholesterol is transferred from HDL via SR-BI to the liver, which ultimately results in the excretion of cholesterol via bile and feces in what is known as the reverse cholesterol transport pathway. Much of our knowledge of SR-BI hepatic function and regulation is derived from mouse models and in vitro characterization. Multiple independent regulatory mechanisms of SR-BI have been discovered that operate at the transcriptional and post-transcriptional levels. In this review we summarize the critical discoveries relating to hepatic SR-BI cholesterol metabolism, atherosclerosis, and regulation of SR-BI, as well as alternative functions that may indirectly affect atherosclerosis.

Human coding variants in scavenger receptor class B member 1 (SR-BI; gene name SCARB1) have recently been identified as being associated with plasma levels of HDL cholesterol. However, a link between coding variants and atherosclerosis has not yet been established. In this study we set out to examine the impact of a SR-BI coding variant in vivo. A mouse model with a coding variant in SR-BI (I179N), identified through a mutagenesis screen, was crossed with Ldlr (-/-) mice, and these mice were maintained on a Western-type diet to promote atherosclerosis. Mice showed 56 and 125 % increased atherosclerosis in female and male Ldlr (-/-) Scarb1 (I179N) mice, respectively, when compared to gender-matched Ldlr (-/-) control mice. As expected, HDL cholesteryl ester uptake was impaired in Ldlr (-/-) Scarb1 (I179N) mice compared to Ldlr (-/-) control mice, with a net effect of increased small and very small LDL cholesterol in Ldlr (-/-) Scarb1 (I179N) mice being the most probable cause of the observed increased atherosclerosis. Our data show that non-null coding variants in SR-BI can have a large significant impact on atherosclerosis, even if plasma lipid levels are not dramatically affected, and that human mutations in other candidate lipid genes could significantly impact atherosclerosis.