SummaryBackgroundStents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy.MethodsThe International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470.FindingsThe trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4·0%) events of disabling stroke or death in the stenting group compared with 27 (3·2%) events in the endarterectomy group (hazard ratio [HR] 1·28, 95% CI 0·77–2·11). The incidence of stroke, death, or procedural myocardial infarction was 8·5% in the stenting group compared with 5·2% in the endarterectomy group (72 vs 44 events; HR 1·69, 1·16–2·45, p=0·006). Risks of any stroke (65 vs 35 events; HR 1·92, 1·27–2·89) and all-cause death (19 vs seven events; HR 2·76, 1·16–6·56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0·0197).InterpretationCompletion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.FundingMedical Research Council, the Stroke Association, Sanofi-Synthélabo, European Union.

Patient-specific medical simulation holds the promise of determining tailored medical treatment based on the characteristics of an individual patient (for example, using a genotypic assay of a sequence of DNA). Decision-support systems based on patient-specific simulation can potentially revolutionize the way that clinicians plan courses of treatment for various conditions, ranging from viral infections to arterial abnormalities. Basing medical decisions on the results of simulations that use models derived from data specific to the patient in question means that the effectiveness of a range of potential treatments can be assessed before they are actually administered, preventing the patient from experiencing unnecessary or ineffective treatments. We illustrate the potential for patient-specific simulation by first discussing the scale of the evolving international grid infrastructure that is now available to underpin such applications. We then consider two case studies, one concerned with the treatment of patients with HIV/AIDS and the other addressing neuropathologies associated with the intracranial vasculature. Such patient-specific medical simulations require access to both appropriate patient data and the computational resources on which to perform potentially very large simulations. Computational infrastructure providers need to furnish access to a wide range of different types of resource, typically made available through heterogeneous computational grids, and to institute policies that facilitate the performance of patient-specific simulations on those resources. To support these kinds of simulations, where life and death decisions are being made, computational resource providers must give urgent priority to such jobs, for example by allowing them to pre-empt the queue on a machine and run straight away. We describe systems that enable such priority computing.

The outlook for children with VGM is significantly better since the advent of endovascular treatment. Decisions about the appropriateness and timing of treatment should be taken by an experienced multidisciplinary team.

Background and Purpose— In ischemic stroke, body temperature is associated with functional outcome. However, the relationship between temperature and outcome may differ in the intraischemic and postischemic phases of stroke. We aimed to determine whether body temperature before or after endovascular thrombectomy (EVT) for large vessel occlusion stroke is associated with clinical outcomes. Methods— Consecutive EVT patients were identified from a prospective registry. Temperature measurements within 24 hours of admission were stratified into pre-EVT (preprocedural and intraprocedural) and post-EVT measurements, which served as surrogates for the intraischemic and postischemic phases of large vessel occlusion stroke, respectively. The primary outcome was functional independence, defined as a modified Rankin Scale score of 0, 1, or 2 at 3 months. Secondary outcomes included the ordinal shift of modified Rankin Scale scores at 3 months, symptomatic intracerebral hemorrhage, and mortality at 3 months. Results— Four hundred thirty-two participants were included (59% men, mean±SD age 65.6±15.7 years). Multivariable logistic regression demonstrated that higher median pre-EVT temperature (per 1°C increase) was an independent predictor of reduced functional independence (odds ratio [OR], 0.66 [95% CI, 0.46–0.94]; P =0.02), poorer modified Rankin Scale scores (common OR, 1.42 [95% CI, 1.08–1.85]; P =0.01), and increased mortality (OR, 1.65 [95% CI, 1.02–2.69]; P =0.04). Peak post-EVT temperature (per 1°C increase) was a significant predictor of elevated modified Rankin Scale scores (common OR, 1.39 [95% CI, 1.03–1.90]; P =0.03) and higher mortality (OR, 1.66 [95% CI, 1.04–2.67]; P =0.03). Conclusions— In patients with large vessel occlusion stroke treated with EVT, higher body temperatures during both the intraischemic and postischemic phases were associated with poorer clinical outcomes. Future research investigating the maintenance of normothermia or therapeutic hypothermia in patients needing to be transferred from primary to EVT-capable stroke centers could be considered.

ObjectiveDescribe the course and outcomes in a UK national cohort of neonates with vein of Galen malformation identified before 28 days of life.MethodsNeonates with angiographically confirmed vein of Galen malformation presenting to 1 of 2 UK treatment centers (2006–2016) were included; those surviving were invited to participate in neurocognitive assessment. Results in each domain were dichotomized into “good” and “poor” categories. Cross‐sectional and angiographic brain imaging studies were systematically interrogated. Logistic regression was used to explore potential outcome predictors.ResultsOf 85 children with neonatal vein of Galen malformation, 51 had survived. Thirty‐four participated in neurocognitive assessment. Outcomes were approximately evenly split between “good” and “poor” categories across all domains, namely, neurological status, general cognition, neuromotor skills, adaptive behavior, and emotional and behavioral development. Important predictors of poor cognitive outcome were initial Bicêtre score ≤ 12 and presence of brain injury, specifically white matter injury, on initial imaging; in multivariate analysis, only Bicêtre score ≤ 12 remained significant.InterpretationDespite modern supportive and endovascular treatment, more than one‐third of unselected newborns with vein of Galen malformation did not survive. Outcome was good in around half of survivors. The importance of white matter injury suggests that abnormalities of venous as well as arterial circulation are important in the pathophysiology of brain injury. Ann Neurol 2018;84:547–555