Efficacy of statins in familial hypercholesterolaemia: a long term cohort study

Objective To determine the efficacy of statin treatment on risk of coronary heart disease in patients with familial hypercholesterolaemia

Identification of imaging selection patterns in acute ischemic stroke patients and the influence on treatment and clinical trial enrolment decision making

For the STroke Imaging Research (STIR) and VISTA-Imaging Investigators The purpose of this study was to collect precise information on the typical imaging decisions given specific clinical acute stroke scenarios. Stroke centers worldwide were surveyed regarding typical imaging used to work up representative acute stroke patients, make treatment decisions, and willingness to enroll in clinical trials. STroke Imaging Research and Virtual International Stroke Trials Archive-Imaging circulated an online survey of clinical case vignettes through its website, the websites of national professional societies from multiple countries as well as through email distribution lists from STroke Imaging Research and participating societies. Survey responders were asked to select the typical imaging work-up for each clinical vignette presented. Actual images were not presented to the survey responders. Instead, the survey then displayed several types of imaging findings offered by the imaging strategy, and the responders selected the appropriate therapy and whether to enroll into a clinical trial considering time from onset, clinical presentation, and imaging findings. A follow-up survey focusing on 6 h from onset was conducted after the release of the positive endovascular trials. We received 548 responses from 35 countries including 282 individual centers; 78% of the centers originating from Australia, Brazil, France, Germany, Spain, United Kingdom, and United States. The specific onset windows presented influenced the type of imaging work-up selected more than the clinical scenario. Magnetic Resonance Imaging usage (27-28%) was substantial, in particular for wake-up stroke. Following the release of the positive trials, selection of perfusion imaging significantly increased for imaging strategy. Usage of vascular or perfusion imaging by Computed Tomography or Magnetic Resonance Imaging beyond just parenchymal imaging was the primary work-up (62-87%) across all clinical vignettes and time windows. Perfusion imaging with Computed Tomography or Magnetic Resonance Imaging was associated with increased probability of enrollment into clinical trials for 0-3 h. Following the release of the positive endovascular trials, selection of endovascular only treatment for 6 h increased across all clinical vignettes

Association Between Intravenous Thrombolysis and Clinical Outcomes Among Patients With Ischemic Stroke and Unsuccessful Mechanical Reperfusion.

IMPORTANCE Clinical evidence of the potential treatment benefit of intravenous thrombolysis preceding unsuccessful mechanical thrombectomy (MT) is scarce. OBJECTIVE To determine whether intravenous thrombolysis (IVT) prior to unsuccessful MT improves functional outcomes in patients with acute ischemic stroke. DESIGN, SETTING, AND PARTICIPANTS Patients were enrolled in this retrospective cohort study from the prospective, observational, multicenter German Stroke Registry-Endovascular Treatment between May 1, 2015, and December 31, 2021. This study compared IVT plus MT vs MT alone in patients with acute ischemic stroke due to anterior circulation large-vessel occlusion in whom mechanical reperfusion was unsuccessful. Unsuccessful mechanical reperfusion was defined as failed (final modified Thrombolysis in Cerebral Infarction grade of 0 or 1) or partial (grade 2a). Patients meeting the inclusion criteria were matched by treatment group using 1:1 propensity score matching. INTERVENTIONS Mechanical thrombectomy with or without IVT. MAIN OUTCOMES AND MEASURES Primary outcome was functional independence at 90 days, defined as a modified Rankin Scale score of 0 to 2. Safety outcomes were the occurrence of symptomatic intracranial hemorrhage and death. RESULTS After matching, 746 patients were compared by treatment arms (median age, 78 [IQR, 68-84] years; 438 women [58.7%]). The proportion of patients who were functionally independent at 90 days was 68 of 373 (18.2%) in the IVT plus MT and 42 of 373 (11.3%) in the MT alone group (adjusted odds ratio [AOR], 2.63 [95% CI, 1.41-5.11]; P = .003). There was a shift toward better functional outcomes on the modified Rankin Scale favoring IVT plus MT (adjusted common OR, 1.98 [95% CI, 1.35-2.92]; P < .001). The treatment benefit of IVT was greater in patients with partial reperfusion compared with failed reperfusion. There was no difference in symptomatic intracranial hemorrhages between treatment groups (AOR, 0.71 [95% CI, 0.29-1.81]; P = .45), while the death rate was lower after IVT plus MT (AOR, 0.54 [95% CI, 0.34-0.86]; P = .01). CONCLUSIONS AND RELEVANCE These findings suggest that prior IVT was safe and improved functional outcomes at 90 days. Partial reperfusion was associated with a greater treatment benefit of IVT, indicating a positive interaction between IVT and MT. These results support current guidelines that all eligible patients with stroke should receive IVT before MT and add a new perspective to the debate on noninferiority of combined stroke treatment

Risk of intracerebral haemorrhage with alteplase after acute ischaemic stroke : a secondary analysis of an individual patient data meta-analysis

Background Randomised trials have shown that alteplase improves the odds of a good outcome when delivered within 4.5 h of acute ischaemic stroke. However, alteplase also increases the risk of intracerebral haemorrhage; we aimed to determine the proportional and absolute effects of alteplase on the risks of intracerebral haemorrhage, mortality, and functional impairment in different types of patients. Methods We used individual patient data from the Stroke Thrombolysis Trialists' (STT) meta-analysis of randomised trials of alteplase versus placebo (or untreated control) in patients with acute ischaemic stroke. We prespecified assessment of three classifications of intracerebral haemorrhage: type 2 parenchymal haemorrhage within 7 days; Safe Implementation of Thrombolysis in Stroke Monitoring Study's (SITS-MOST) haemorrhage within 24-36 h (type 2 parenchymal haemorrhage with a deterioration of at least 4 points on National Institutes of Health Stroke Scale [NIHSS]); and fatal intracerebral haemorrhage within 7 days. We used logistic regression, stratified by trial, to model the log odds of intracerebral haemorrhage on allocation to alteplase, treatment delay, age, and stroke severity. We did exploratory analyses to assess mortality after intracerebral haemorrhage and examine the absolute risks of intracerebral haemorrhage in the context of functional outcome at 90-180 days. Findings Data were available from 6756 participants in the nine trials of intravenous alteplase versus control. Alteplase increased the odds of type 2 parenchymal haemorrhage (occurring in 231 [6.8%] of 3391 patients allocated alteplase vs 44 [1.3%] of 3365 patients allocated control; odds ratio [OR] 5.55 [95% CI 4.01-7.70]; absolute excess 5.5% [4.6-6.4]); of SITS-MOST haemorrhage (124 [3.7%] of 3391 vs 19 [0.6%] of 3365; OR 6.67 [4.11-10.84]; absolute excess 3.1% [2.4-3.8]); and of fatal intracerebral haemorrhage (91 [2.7%] of 3391 vs 13 [0.4%] of 3365; OR 7.14 [3.98-12.79]; absolute excess 2.3% [1.7-2.9]). However defined, the proportional increase in intracerebral haemorrhage was similar irrespective of treatment delay, age, or baseline stroke severity, but the absolute excess risk of intracerebral haemorrhage increased with increasing stroke severity: for SITS-MOST intracerebral haemorrhage the absolute excess risk ranged from 1.5% (0.8-2.6%) for strokes with NIHSS 0-4 to 3.7% (2.1-6.3%) for NIHSS 22 or more (p=0.0101). For patients treated within 4.5 h, the absolute increase in the proportion (6.8% [4.0% to 9.5%]) achieving a modified Rankin Scale of 0 or 1 (excellent outcome) exceeded the absolute increase in risk of fatal intracerebral haemorrhage (2.2% [1.5% to 3.0%]) and the increased risk of any death within 90 days (0.9% [-1.4% to 3.2%]). Interpretation Among patients given alteplase, the net outcome is predicted both by time to treatment (with faster time increasing the proportion achieving an excellent outcome) and stroke severity (with a more severe stroke increasing the absolute risk of intracerebral haemorrhage). Although, within 4.5 h of stroke, the probability of achieving an excellent outcome with alteplase treatment exceeds the risk of death, early treatment is especially important for patients with severe stroke.Peer reviewe

Early postoperative MRI overestimates residual tumour after resection of gliomas with no or minimal enhancement

Standards for residual tumour measurement after resection of gliomas with no or minimal enhancement have not yet been established. In this study residual volumes on early and late postoperative T2-/FLAIR-weighted MRI are compared. A retrospective cohort included 58 consecutive glioma patients with no or minimal preoperative gadolinium enhancement. Inclusion criteria were first-time resection between 2007 and 2009 with a T2-/FLAIR-based target volume and availability of preoperative, early (<48 h) and late (1-7 months) postoperative MRI. The volumes of non-enhancing T2/FLAIR tissue and diffusion restriction areas were measured. Residual tumour volumes were 22% smaller on late postoperative compared with early postoperative T2-weighted MRI and 49% smaller for FLAIR-weighted imaging. Postoperative restricted diffusion volume correlated with the difference between early and late postoperative FLAIR volumes and with the difference between T2 and FLAIR volumes on early postoperative MRI. We observed a systematic and substantial overestimation of residual non-enhancing volume on MRI within 48 h of resection compared with months postoperatively, in particular for FLAIR imaging. Resection-induced ischaemia contributes to this overestimation, as may other operative effects. This indicates that early postoperative MRI is less reliable to determine the extent of non-enhancing residual glioma and restricted diffusion volumes are imperativ

Predictions for cold nuclear matter effects in p plus Pb collisions at root SNN =8.16 TeV

Predictions for cold nuclear matter effects on charged hadrons, identified light hadrons, quarkonium and heavy flavor hadrons, Drell-Yan dileptons, jets, photons, gauge bosons and top quark pairs produced in p+Pb collisions at, root S-NN = 8.16 TeV are compiled and, where possible, compared to each other. Predictions of the normalized ratios of p+Pb to p+ p cross sections are also presented for most of the observables, providing new insights into the expected role of cold nuclear matter effects. In particular, the role of nuclear parson distribution functions on particle production can now be probed over a wider range of phase space than ever before. (C) 2018 Elsevier B.V. All rights reserved.Peer reviewe

Details of a prospective protocol for a collaborative meta-analysis of individual participant data from all randomized trials of intravenous rt-PA vs. control:statistical analysis plan for the Stroke Thrombolysis Trialists' Collaborative meta-analysis

RATIONALE: Thrombolysis with intravenous alteplase is both effective and safe when administered to particular types of patient within 4·5 hours of having an ischemic stroke. However, the extent to which effects might vary in different types of patient is uncertain. AIMS AND DESIGN: We describe the protocol for an updated individual patient data meta-analysis of trials of intravenous alteplase, including results from the recently reported third International Stroke Trial, in which a wide range of patients enrolled up to six-hours after stroke onset were randomized to alteplase vs. control. STUDY OUTCOMES: This protocol will specify the primary outcome for efficacy, specified prior to knowledge of the results from the third International Stroke Trial, as the proportion of patients having a 'favorable' stroke outcome, defined by modified Rankin Score 0-1 at final follow-up at three- to six-months. The primary analysis will be to estimate the extent to which the known benefit of alteplase on modified Rankin Score 0-1 diminishes with treatment delay, and the extent to which it is independently modified by age and stroke severity. Key secondary outcomes include effect of alteplase on death within 90 days; analyses of modified Rankin Score using ordinal, rather than dichotomous, methods; and effects of alteplase on symptomatic intracranial hemorrhage, fatal intracranial hemorrhage, symptomatic ischemic brain edema and early edema, effacement and/or midline shift. DISCUSSION: This collaborative meta-analysis of individual participant data from all randomized trials of intravenous alteplase vs. control will demonstrate how the known benefits of alteplase on ischemic stroke outcome vary across different types of patient