Risk of recurrent arterial ischemic stroke in childhood: A prospective international study

Background and Purpose - Published cohorts of children with arterial ischemic stroke (AIS) in the 1990s to early 2000s reported 5-year cumulative recurrence rates approaching 20%. Since then, utilization of antithrombotic agents for secondary stroke prevention in children has increased. We sought to determine rates and predictors of recurrent stroke in the current era. Methods - The Vascular Effects of Infection in Pediatric Stroke (VIPS) study enrolled 355 children with AIS at 37 international centers from 2009 to 2014 and followed them prospectively for recurrent stroke. Index and recurrent strokes underwent central review and confirmation, as well as central classification of causes of stroke, including arteriopathies. Other predictors were measured via parental interview or chart review. Results - Of the 355 children, 354 survived their acute index stroke, and 308 (87%) were treated with an antithrombotic medication. During a median follow-up of 2.0 years (interquartile range, 1.0-3.0), 40 children had a recurrent AIS, and none had a hemorrhagic stroke. The cumulative stroke recurrence rate was 6.8% (95% confidence interval, 4.6%-10%) at 1 month and 12% (8.5%-15%) at 1 year. The sole predictor of recurrence was the presence of an arteriopathy, which increased the risk of recurrence 5-fold when compared with an idiopathic AIS (hazard ratio, 5.0; 95% confidence interval, 1.8-14). The 1-year recurrence rate was 32% (95% confidence interval, 18%-51%) for moyamoya, 25% (12%-48%) for transient cerebral arteriopathy, and 19% (8.5%-40%) for arterial dissection. Conclusions - Children with AIS, particularly those with arteriopathy, remain at high risk for recurrent AIS despite increased utilization of antithrombotic agents. Therapies directed at the arteriopathies themselves are needed

Clinical and Imaging Characteristics of Arteriopathy Subtypes in Children with Arterial Ischemic Stroke: Results of the VIPS Study.

Background and purposeChildhood arteriopathies are rare but heterogenous, and difficult to diagnose and classify, especially by nonexperts. We quantified clinical and imaging characteristics associated with childhood arteriopathy subtypes to facilitate their diagnosis and classification in research and clinical settings.Materials and methodsThe Vascular Effects of Infection in Pediatric Stroke (VIPS) study prospectively enrolled 355 children with arterial ischemic stroke (2010-2014). A central team of experts reviewed all data to diagnose childhood arteriopathy and classify subtypes, including arterial dissection and focal cerebral arteriopathy-inflammatory type, which includes transient cerebral arteriopathy, Moyamoya disease, and diffuse/multifocal vasculitis. Only children whose stroke etiology could be conclusively diagnosed were included in these analyses. We constructed logistic regression models to identify characteristics associated with each arteriopathy subtype.ResultsAmong 127 children with definite arteriopathy, the arteriopathy subtype could not be classified in 18 (14%). Moyamoya disease (n = 34) occurred mostly in children younger than 8 years of age; focal cerebral arteriopathy-inflammatory type (n = 25), in children 8-15 years of age; and dissection (n = 26), at all ages. Vertigo at stroke presentation was common in dissection. Dissection affected the cervical arteries, while Moyamoya disease involved the supraclinoid internal carotid arteries. A banded appearance of the M1 segment of the middle cerebral artery was pathognomonic of focal cerebral arteriopathy-inflammatory type but was present in <25% of patients with focal cerebral arteriopathy-inflammatory type; a small lenticulostriate distribution infarct was a more common predictor of focal cerebral arteriopathy-inflammatory type, present in 76%. It remained difficult to distinguish focal cerebral arteriopathy-inflammatory type from intracranial dissection of the anterior circulation. We observed only secondary forms of diffuse/multifocal vasculitis, mostly due to meningitis.ConclusionsChildhood arteriopathy subtypes have some typical features that aid diagnosis. Better imaging methods, including vessel wall imaging, are needed for improved classification of focal cerebral arteriopathy of childhood

Ethnicity and thrombolysis in ischemic stroke: a hospital based study in Amsterdam

<p>Abstract</p> <p>Background</p> <p>Ethnic differences have been reported with regard to several medical therapies. The aim of this study was to investigate the relation between ethnicity and thrombolysis in stroke patients.</p> <p>Methods</p> <p>Retrospective single-centre study. Patients admitted with an ischemic stroke between 2003 and 2008 were included. Ethnicity was determined by self-identification and stratified into white and non-white (all other ethnicities). The main outcome measure was the difference in thrombolysis rate between white and non-white patients. Logistic regression analysis was used to identify potential confounders of the relation between ethnicity and thrombolysis.</p> <p>Results</p> <p>510 patients were included, 392 (77%) white and 118 (23%) non-white. Non-white patients were younger (median 69 vs. 60 years, p < 0.001), had a higher blood pressure at admission (median systolic 150 vs. 160 mmHg, p = 0.02) and a lower stroke severity (median NIHSS 5 vs. 4, p = 0.04). Non-white patients were significantly less often treated with thrombolysis compared to white patients (odds ratio 0.34, 95% CI 0.17-0.71), which was partly explained by a later arrival at the hospital. After adjustment for potential confounders (late arrival, age, blood pressure above upper limit for thrombolysis, and oral anticoagulation use), a trend towards a lower thrombolysis rate in non-whites remained (adjusted odds ratio 0.38, 95% CI 0.13 to 1.16).</p> <p>Conclusions</p> <p>Non-white stroke patients less often received thrombolysis than white patients, partly as a result of a delay in presentation. In this single centre study, potential bias due to hospital differences or insurance status could be ruled out as a cause. The magnitude of the difference is worrisome and requires further investigation. Modifiable causes, such as patient delay, awareness of stroke symptoms, language barriers and treatment of cardiovascular risk factors, should be addressed specifically in these ethnic groups in future stroke campaigns.</p

First measurement of the |t|-dependence of coherent J/ψ photonuclear production

The first measurement of the cross section for coherent J/ψ photoproduction as a function of |t|, the square of the momentum transferred between the incoming and outgoing target nucleus, is presented. The data were measured with the ALICE detector in ultra-peripheral Pb–Pb collisions at a centre-of-mass energy per nucleon pair sNN=5.02TeV with the J/ψ produced in the central rapidity region |y|<0.8, which corresponds to the small Bjorken-x range (0.3−1.4)×10−3. The measured |t|-dependence is not described by computations based only on the Pb nuclear form factor, while the photonuclear cross section is better reproduced by models including shadowing according to the leading-twist approximation, or gluon-saturation effects from the impact-parameter dependent Balitsky–Kovchegov equation. These new results are therefore a valid tool to constrain the relevant model parameters and to investigate the transverse gluonic structure at very low Bjorken-x.publishedVersio

The 2014 ALMA Long Baseline Campaign: An Overview

A major goal of the Atacama Large Millimeter/submillimeter Array (ALMA) is to make accurate images with resolutions of tens of milliarcseconds, which at submillimeter (submm) wavelengths requires baselines up to ~15 km. To develop and test this capability, a Long Baseline Campaign (LBC) was carried out from September to late November 2014, culminating in end-to-end observations, calibrations, and imaging of selected Science Verification (SV) targets. This paper presents an overview of the campaign and its main results, including an investigation of the short-term coherence properties and systematic phase errors over the long baselines at the ALMA site, a summary of the SV targets and observations, and recommendations for science observing strategies at long baselines. Deep ALMA images of the quasar 3C138 at 97 and 241 GHz are also compared to VLA 43 GHz results, demonstrating an agreement at a level of a few percent. As a result of the extensive program of LBC testing, the highly successful SV imaging at long baselines achieved angular resolutions as fine as 19 mas at ~350 GHz. Observing with ALMA on baselines of up to 15 km is now possible, and opens up new parameter space for submm astronomy

Resolving the strange behavior of extraterrestrial potassium in the upper atmosphere

It has been known since the 1960s that the layers of Na and K atoms, which occur between 80 and 105 km in the Earth's atmosphere as a result of meteoric ablation, exhibit completely different seasonal behavior. In the extratropics Na varies annually, with a pronounced wintertime maximum and summertime minimum. However, K varies semiannually with a small summertime maximum and minima at the equinoxes. This contrasting behavior has never been satisfactorily explained. Here we use a combination of electronic structure and chemical kinetic rate theory to determine two key differences in the chemistries of K and Na. First, the neutralization of K+ ions is only favored at low temperatures during summer. Second, cycling between K and its major neutral reservoir KHCO3 is essentially temperature independent. A whole atmosphere model incorporating this new chemistry, together with a meteor input function, now correctly predicts the seasonal behavior of the K layer

A systematic review of endpoint definitions in late phase pulmonary tuberculosis therapeutic trials.

BackgroundSafe, more efficacious treatments are needed to address the considerable morbidity and mortality associated with pulmonary tuberculosis (TB). However, the current practice in TB therapeutics trials is to use composite binary outcomes, which in the absence of standardization may inflate false positive and negative errors in evaluating regimens. The lack of standardization of outcomes is a barrier to the identification of highly efficacious regimens and the introduction of innovative methodologies METHODS: We conducted a systematic review of trials designed to advance new pulmonary TB drugs or regimens for regulatory approval and inform practice guidelines. Trials were primarily identified from the WHO International Clinical Trial Registry Platform (ICTRP). Only trials that collected post-treatment follow-up data and enrolled at least 100 patients were included. Protocols and Statistical Analysis Plans (SAP) for eligible trials from 1995 to the present were obtained from trial investigators. Details of outcome data, both explicit and implied, were abstracted and organized into three broad categories: favorable, unfavorable, and not assessable. Within these categories, individual trial definitions were recorded and collated, and areas of broad consensus and disagreement were identified and described.ResultsFrom 2205 trials in any way related to TB, 51 were selected for protocol and SAP review, from which 31 were both eligible and had accessible documentation. Within the three designated categories, we found broad consensus in the definitions of favorable and unfavorable outcomes, although specific details were not always provided, and when explicitly addressed, were heterogeneous. Favorable outcomes were handled the most consistently but were widely variable with respect to specification. In some cases, the same events were defined differently by different protocols, particularly in distinguishing unfavorable from not assessable events. Death was often interpreted as conditional on cause. Patients who did not complete the study because of withdrawal or loss to follow-up presented a particular challenge to consistent interpretation and analytic treatment of outcomes.ConclusionsIn a review of 31 clinical trials, we found that outcome definitions were heterogeneous, highlighting the need to establish clearer specification and a move towards universal standardization of outcomes across pulmonary TB trials. The ICH E9 (R1) addendum provides guidelines for undertaking and achieving this goal.Prospero registrationPROSPERO CRD42020197993 . Registration 11 August 2020