International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

Evaluation of Littoral Combat Ships for open-ocean anti-submarine warfare

This report evaluates the Littoral Combat Ship (LCS) and its potential to fulfill the open-ocean anti-submarine warfare (ASW) mission. It is unknown whether the LCS platform can support open-ocean ASW. This report examines which LCS variant, Freedom or Independence, is more suitable for open-ocean ASW. Initial analysis defines the open-ocean ASW problem space in terms of a threat analysis, mission analysis, current Concept of Operations (CONOPS), and current LCS capabilities. An Analysis of Alternatives (AoA) uses derived functional and operational requirements within a Pugh matrix to decide which variant best performs ASW, and what modifications can improve future designs of the LCS. The analysis shows the Freedom class has marginal advantages in performing open-ocean ASW mission tasks, and establishes three areas for improvement: self-noise emissions, weight, and communication. Potential solutions are explored to address these shortfalls and to analyze their impact on LCS’s ability to meet core requirements of the open-ocean ASW mission. This paper concludes that the LCS is capable of fulfilling the open-ocean ASW mission if improvements are made to the design and CONOPS.http://archive.org/details/evaluationoflitt1094548592Approved for public release; distribution is unlimited

Strategies for streamlining emergency stroke care

There has been a tremendous evolution in the stroke systems of care in the USA. Public awareness, prehospital care, and in-hospital protocols have never been so effectively connected. However, given the critical role of time to effective reperfusion in the setting of acute ischemic stroke, it is vital and timely to implement strategies to further streamline emergency stroke care. This article reviews the most current standards and guidelines related to the flow of stroke care in the prehospital and emergency settings

Topography of Vertebral Artery Origin Plaques: Characteristics and Determinants

Atherosclerotic plaques located at the vertebral artery ostium (VAo) are a mechanism for posterior circulation stroke, but little is known about VAo plaque topography and formation. In this study, we describe the topography of atherosclerotic plaques involving the origin of the vertebral artery (VA). Cross-sectional analyses of extracranial duplex studies were performed, and VAo plaques were classified based on their topography in 3 groups: (1) exclusively at the VA ostium; (2) predominantly subclavian, with extension into the vertebral ostium; and (3) predominantly ostial, with extension into the subclavian artery). Chi-square and analysis of variance tests were performed to investigate the association between VAo plaque topography and continuous and categorical variables, respectively. A total of 99 of 481 (21%) ultrasound duplex studies showed VAo plaques. The majority of the plaques (60%) were found to extend from the subclavian to the ostium. Plaques occurred more frequently at the medial wall of the VAo. No vascular risk factors were associated with plaque formation; however, women were more likely to have plaques involving predominantly or exclusively the VAo (P = .004). We describe 3 different patterns of VAo involvement in patients with ostial atherosclerotic VA disease. VAo plaques occurred almost exclusively at the medial wall of the vessel. Women had more plaques involving predominantly the origin. Prospective studies are needed to investigate the clinical significance of these findings

Severe Neovascular Glaucoma Exacerbation as a Complication of Carotid Artery Stenting: A Case Report

Introduction: Neovascular glaucoma (NVG) has been rarely reported as an acute complication of carotid endarterectomy, but there is scant literature available regarding this potential condition following carotid artery stenting (CAS). We present a case of severe worsening of NVG occurring after bilateral CAS with progressive deterioration of vision ultimately leading to blindness. Case Description: A 66-year-old male with multiple stroke risk factors, bilateral cataract extraction, proliferative diabetic retinopathy of left eye, and nonproliferative diabetic retinopathy of right eye, and prior left eye pars plana vitrectomy presented with episodes of transient right eye vision loss in context of bilateral high-grade internal carotid artery stenoses. He underwent right CAS with subsequent elevation of bilateral intraocular pressures (IOPs) concerning for acute NVG. Over time, the patient had some interval improvement in IOPs and underwent planned left CAS. After the procedure, he again developed elevated IOPs, concerning for acute NVG which eventually led to right eye pars plana vitrectomy for vitreous hemorrhage and refractory IOP elevation. At 6-month follow-up from initial stenting, the patient was blind in both eyes. Discussion: We present a case of recurrent IOP elevations following CAS eventually resulting in bilateral eye blindness. This case is important not only as an illustration of an underrecognized postprocedural CAS complication but also as a demonstration of likely elevated risk of NVG following CAS for patients with other predisposing risk factors for ocular hypertension such as glaucoma, proliferative diabetic retinopathy, prior cataract extraction, and prior pars plana vitrectomy

Transradial access in acute ischemic stroke intervention

To describe the feasibility and safety of transradial access (TRA) in the interventional management of acute ischemic stroke (AIS). A retrospective review of the local institutional AIS interventional databases of three tertiary academic centers was performed and the use of TRA identified. TRA was attempted in 15 (1.5%) of 1001 patients; it was used in 12 cases due to transfemoral access (TFA) failure and in 3 as the primary strategy. The mean age was 72.3±8.6 and 46% were male. Baseline National Institutes of Health Stroke Scale score was 19.5±8.7, two patients (14%) received intravenous tissue plasminogen activator, and mean time from last known normal to intra-arterial therapy was 17.0±20.1 h. Five patients had anterior circulation occlusive disease and 10 had vertebrobasilar occlusions. TRA was effective in allowing clot engagement in 13 of 15 cases: one patient had a hypoplastic radial artery that precluded sheath advancement and one had chronic innominate artery occlusion that could not be crossed. Mean time to switch from TFA to TRA was 1.9±1.3 h and the mean time from radial puncture to reperfusion was 2.2±1.0 h. Modified Thrombolysis In Cerebral Infarction 2b-3 reperfusion via TRA was achieved in 9 of 15 patients (60%). No radial puncture site complications were noted. At 90 days, two patients (13%) had a good clinical outcome and seven (50%) had died. Failure of TFA in the endovascular treatment of AIS is uncommon but leads to unacceptable delays in reperfusion and poor outcomes. Standardization of benchmarks for access switch could serve as a guide for neurointerventionalists. TRA is a valid approach for the endovascular treatment of AIS

Abstract P104: Incidence, Characteristics and Outcomes of Large Vessel Stroke in Covid-19: An International Multicenter Study

Background: While there are reports of acute ischemic stroke (AIS) in COVID-19 patients, the overall incidence of acute ischemic stroke and clinical characteristics of large vessel occlusion in such patient remains to be established. Methods: A retrospective, international multicenter study of large vessel occlusion (LVO) was undertaken from March 1 to May 1, 2020 at 12 stroke centers from 4 countries. Detailed data were collected on consecutive LVOs in hospitalized patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the incidence of AIS/LVO was measured. Among patients who underwent mechanical thrombectomy, stroke outcomes along with COVID-19 symptoms were reported. Results: Out of a total of 6698 COVID-19 patients admitted to 10 stroke centers, the incidence of stroke was found to be 1.3% (range 0.6-2.6%). The median age of patients who presented with LVO was 51 years (range 27-87) and in the US centers, African Americans comprised 28% of all patients. Ten patients (16 %) were less than 50 years of age with no significant risk factors for LVOs the vast majority. Among the LVOs eligible for MT, the average time to presentation from symptom onset to presentation was 9.3 hours. Successful revascularization was achieved in 81% of patients and the intracranial hemorrhage rate was 14% with no symptomatic hemorrhages. Twenty-one (50%) patients were either discharged to home or to acute rehabilitation facilities. Conclusion: LVOs was predominant in patients with AIS and COVID-19, occurring at a significantly younger age and affecting African Americans disproportionately

Incidence, Characteristics and Outcomes of Large Vessel Stroke in COVID-19 Cohort: An International Multicenter Study

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