Warfarin vs aspirin for symptomatic intracranial stenosis: subgroup analyses from WASID

The WASID trial showed no advantage of warfarin over aspirin for preventing the primary endpoint of ischemic stroke, brain hemorrhage, or vascular death. In analyses of selected subgroups, there was no definite benefit from warfarin. Warfarin reduced the risk of the primary endpoint among patients with basilar artery stenosis, but there was no reduction in stroke in the basilar artery territory or benefit for vertebral artery stenosis or posterior circulation disease in general.     

Symptomatic cerebral air embolism during neuro-angiographic procedures: incidence and problem avoidance

Background  

While clinically symptomatic cerebral air embolism secondary to neuro-angiographic procedures is rare, the incidence in a large series of procedures is unknown. Understanding this complication’s frequency and etiology is critical if systems are to be instituted to reduce its incidence.     

Nilotinib-Associated Atherosclerosis Presenting as Multifocal Intracranial Stenosis and Acute Stroke

Nilotinib, a BCR-ABL tyrosine kinase inhibitor (TKI), has been associated with vascular events and accelerated arterial stenosis, presumably of atherosclerotic etiology. Studies of nilotinib-associated atherosclerosis are mainly associated with progressive peripheral artery occlusive disease (PAOD), and only a few cases of coronary artery disease (CAD), and cerebrovascular disease (CVD) have been reported. The mechanisms by which nilotinib promotes atherosclerosis are poorly understood but endothelial and perivascular factors, mast cell depletion, and metabolic factors such as promotion of dyslipidemia and impaired glucose metabolism are thought to play a role. We present a case of a patient with chronic myelogenous leukemia (CML) treated with nilotinib who developed intracranial atherosclerosis leading to acute onset of stroke. Our patient had no cardiovascular risk factors prior to treatment with nilotinib and developed accelerated atheromatous cerebrovascular disease with severe left middle cerebral artery (MCA) stenosis. These findings suggest that nilotinib may be associated with the development of intracranial atherosclerotic disease (ICAD) independently of any preexisting vascular risk factors leading to acute stroke. Clinicians should have increased awareness of the association between nilotinib and the development of progressive atheromatous disease and vascular adverse events including PAOD, CAD, and CVD. In certain patients, these events can be severe and life threatening. Thus, screening for vascular risk factors including CVD prior to starting nilotinib and close follow up during treatment is crucial.     

Structural basis for dual roles of Aar2p in U5 snRNP assembly

Yeast U5 small nuclear ribonucleoprotein particle (snRNP) is assembled via a cytoplasmic precursor that contains the U5-specific Prp8 protein but lacks the U5-specific Brr2 helicase. Instead, pre-U5 snRNP includes the Aar2 protein not found in mature U5 snRNP or spliceosomes. Aar2p and Brr2p bind competitively to a C-terminal region of Prp8p that comprises consecutive RNase H-like and Jab1/MPN-like domains. To elucidate the molecular basis for this competition, we determined the crystal structure of Aar2p in complex with the Prp8p RNase H and Jab1/MPN domains. Aar2p binds on one side of the RNase H domain and extends its C terminus to the other side, where the Jab1/MPN domain is docked onto a composite Aar2p–RNase H platform. Known Brr2p interaction sites of the Jab1/MPN domain remain available, suggesting that Aar2p-mediated compaction of the Prp8p domains sterically interferes with Brr2p binding. Moreover, Aar2p occupies known RNA-binding sites of the RNase H domain, and Aar2p interferes with binding of U4/U6 di-snRNA to the Prp8p C-terminal region. Structural and functional analyses of phospho-mimetic mutations reveal how phosphorylation reduces affinity of Aar2p for Prp8p and allows Brr2p and U4/U6 binding. Our results show how Aar2p regulates both protein and RNA binding to Prp8p during U5 snRNP assembly.     

Atrial fibrillation at discharge from the hospital in patients undergoing mitral valve repair

BACKGROUND: Patients undergoing mitral valve repair (MVRr) are often discharged on oral anticoagulation with warfarin. Because the decision about oral anticoagulation is made at discharge from the hospital and because atrial fibrillation (AF) represents the only well-documented indication for oral anticoagulation in these patients, we studied the frequency of AF at discharge after MVRr. METHODS: We reviewed the records of 245 patients who underwent MVRr over the past 5 years and assessed the frequency of AF at discharge from the hospital and the factors that were associated with an increased risk for arrhythmia. RESULTS: The group comprised 95 women and 150 men with a mean age of 62.1 +/- 14 years. Seventy-three (30 %) patients were in and/or had a history of AF on admission. Sixty-five (27 %) patients had AF at discharge. Factors that were associated with AF at discharge were: AF on admission (odds ratio [OR] 57.1; confidence interval [CI] 20.8 - 157.3; p < 0.0001), enlarged left atrium (OR 3.2; CI 1.2 - 8.7; p = 0.025) and intake of ACE inhibitors (OR 3.9; CI 1.2 - 12.3; p = 0.022). The OR for AF at discharge in patients with none of the above risk factors was 0.02 (95 % CI 0.02 - 0.13; p < 0.0001). CONCLUSION: Only a relatively small proportion of the studied patients, especially patients with AF on admission, with larger atria and with a history of ACE inhibitors intake, were in AF at discharge after MVRr. Patients with none of these risk factors were at low risk for AF at discharge after MVRr and the optimal oral anticoagulation regimen for these low-risk patients needs to be determined.