Stroke occurs more commonly after carotid artery stenting than after carotid endarterectomy. Details regarding stroke type, severity, and characteristics have not been reported previously. We ...describe the strokes that have occurred in the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST).
CREST is a randomized, open-allocation, controlled trial with blinded end-point adjudication. Stroke was a component of the primary composite outcome. Patients who received their assigned treatment within 30 days of randomization were included. Stroke was adjudicated by a panel of board-certified vascular neurologists with secondary central review of clinically obtained brain images. Stroke type, laterality, timing, and outcome were reported. A periprocedural stroke occurred among 81 of the 2502 patients randomized and among 69 of the 2272 in the present analysis. Strokes were predominantly minor (81%, n=56), ischemic (90%, n=62), in the anterior circulation (94%, n=65), and ipsilateral to the treated artery (88%, n=61). There were 7 hemorrhages, which occurred 3 to 21 days after the procedure, and 5 were fatal. Major stroke occurred in 13 (0.6%) of the 2272 patients. The estimated 4-year mortality after stroke was 21.1% compared with 11.6% for those without stroke. The adjusted risk of death at 4 years was higher after periprocedural stroke (hazard ratio, 2.78; 95% confidence interval, 1.63-4.76).
Stroke, particularly severe stroke, was uncommon after carotid intervention in CREST, but stroke was associated with significant morbidity and was independently associated with a nearly 3-fold increased future mortality. The delayed timing of major and hemorrhagic stroke after revascularization suggests that these strokes may be preventable.
To compare fotemustine and dacarbazine (DTIC) in terms of overall response rate (ORR) as primary end-point and overall survival, duration of responses, time to progression, time to occurrence of ...brain metastases (BM), and to assess safety and quality of life in patients with disseminated cutaneous melanoma.
Patients received either intravenous fotemustine 100 mg/m2 weekly for 3 weeks or DTIC 250 mg/m2/d for 5 consecutive days every 4 weeks (two cycles). Nonprogressive patients received a maintenance treatment every 4 weeks (fotemustine 100 mg/m2 or DTIC 250 mg/m2 for 5 days).
Two hundred twenty-nine patients were randomly assigned to fotemustine or DTIC arms. The best ORR was higher in the fotemustine arm than in the DTIC arm in the intent-to-treat population (n=229; 15.2% v 6.8%; P=.043) and in full analysis set (n=221) (15.5% v 7.2%; P=.053). Similar median durations of responses (5.8 months with fotemustine v 6.9 months with DTIC) and time to progression (1.8 v 1.9 months, respectively) were observed. In patients without BM at inclusion, the median time to BM was 22.7 months with fotemustine versus 7.2 months with DTIC (P=.059). Median survival was 7.3 months with fotemustine versus 5.6 months with DTIC (P=.067). The main toxicity was grade 3 to 4 neutropenia (51% with fotemustine v 5% with DTIC) and thrombocytopenia (43% v 6%, respectively). No significant difference was noted for quality of life between arms.
ORR was higher in the fotemustine arm compared to the DTIC arm in first-line treatment of disseminated melanoma. A trend in favor of fotemustine in terms of overall survival and time to BM was evidenced.
Summary Background The clinical benefit of preventive eradication of unruptured brain arteriovenous malformations remains uncertain. A Randomised trial of Unruptured Brain Arteriovenous malformations ...(ARUBA) aims to compare the risk of death and symptomatic stroke in patients with an unruptured brain arteriovenous malformation who are allocated to either medical management alone or medical management with interventional therapy. Methods Adult patients (≥18 years) with an unruptured brain arteriovenous malformation were enrolled into this trial at 39 clinical sites in nine countries. Patients were randomised (by web-based system, in a 1:1 ratio, with random permuted block design block size 2, 4, or 6, stratified by clinical site) to medical management with interventional therapy (ie, neurosurgery, embolisation, or stereotactic radiotherapy, alone or in combination) or medical management alone (ie, pharmacological therapy for neurological symptoms as needed). Patients, clinicians, and investigators are aware of treatment assignment. The primary outcome is time to the composite endpoint of death or symptomatic stroke; the primary analysis is by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00389181. Findings Randomisation was started on April 4, 2007, and was stopped on April 15, 2013, when a data and safety monitoring board appointed by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health recommended halting randomisation because of superiority of the medical management group (log-rank Z statistic of 4·10, exceeding the prespecified stopping boundary value of 2·87). At this point, outcome data were available for 223 patients (mean follow-up 33·3 months SD 19·7), 114 assigned to interventional therapy and 109 to medical management. The primary endpoint had been reached by 11 (10·1%) patients in the medical management group compared with 35 (30·7%) in the interventional therapy group. The risk of death or stroke was significantly lower in the medical management group than in the interventional therapy group (hazard ratio 0·27, 95% CI 0·14–0·54). No harms were identified, other than a higher number of strokes (45 vs 12, p<0·0001) and neurological deficits unrelated to stroke (14 vs 1, p=0·0008) in patients allocated to interventional therapy compared with medical management. Interpretation The ARUBA trial showed that medical management alone is superior to medical management with interventional therapy for the prevention of death or stroke in patients with unruptured brain arteriovenous malformations followed up for 33 months. The trial is continuing its observational phase to establish whether the disparities will persist over an additional 5 years of follow-up. Funding National Institutes of Health, National Institute of Neurological Disorders and Stroke.
We use a set of hydrodynamical and dark matter-only (DMonly) simulations to calibrate the halo mass function (HMF). We explore the impact of baryons, propose an improved parametrization for spherical ...overdensity masses, and identify differences between our DMonly HMF and previously published HMFs. We use the Magneticum simulations, which are well suited because of their accurate treatment of baryons, high resolution, and large cosmological volumes of up to (3818 Mpc)3. Baryonic effects globally decrease the masses of galaxy clusters, which, at a given mass, results in a decrease of their number density. This effect vanishes at high redshift z ∼ 2 and for high masses M
200 m ≳ 1014 M⊙. We perform cosmological analyses of three idealized approximations to the cluster surveys by the South Pole Telescope (SPT), Planck, and eROSITA. We pursue two main questions. (1) What is the impact of baryons? – for the SPT-like and the Planck-like samples, the impact of baryons on cosmological results is negligible. In the eROSITA-like case, however, neglecting the baryonic impact leads to an underestimate of Ωm by about 0.01, which is comparable to the expected uncertainty from eROSITA. (2) How does our DMonly HMF compare with previous work? – for the Planck-like sample, results obtained using our DMonly HMF are shifted by Δ(σ8) ≃ Δ(σ8(Ωm/0.27)0.3) ≃ 0.02 with respect to results obtained using the Tinker et al. fit. This suggests that using our HMF would shift results from Planck clusters towards better agreement with cosmic-microwave-background anisotropy measurements. Finally, we discuss biases that can be introduced through inadequate HMF parametrizations that introduce false cosmological sensitivity.
We present a measurement of the angular power spectrum of the cosmic microwave background (CMB) using data from the South Pole Telescope (SPT). The data consist of 790 deg2 of sky observed at 150 GHz ...during 2008 and 2009. Here we present the power spectrum over the multipole range 650 < l < 3000, where it is dominated by primary CMB anisotropy. We combine this power spectrum with the power spectra from the seven-year Wilkinson Microwave Anisotropy Probe (WMAP) data release to constrain cosmological models. We find that the SPT and WMAP data are consistent with each other and, when combined, are well fit by a spatially flat, Delta *LCDM cosmological model. The SPT+WMAP constraint on the spectral index of scalar fluctuations is ns = 0.9663 ? 0.0112. We detect, at ~5 Delta *s significance, the effect of gravitational lensing on the CMB power spectrum, and find its amplitude to be consistent with the Delta *LCDM cosmological model. We explore a number of extensions beyond the Delta *LCDM model. Each extension is tested independently, although there are degeneracies between some of the extension parameters. We constrain the tensor-to-scalar ratio to be r < 0.21 (95% CL) and constrain the running of the scalar spectral index to be dns /dln k = --0.024 ? 0.013. We strongly detect the effects of primordial helium and neutrinos on the CMB; a model without helium is rejected at 7.7 Delta *s, while a model without neutrinos is rejected at 7.5 Delta *s. The primordial helium abundance is measured to be Yp = 0.296 ? 0.030, and the effective number of relativistic species is measured to be N eff = 3.85 ? 0.62. The constraints on these models are strengthened when the CMB data are combined with measurements of the Hubble constant and the baryon acoustic oscillation feature. Notable improvements include ns = 0.9668 ? 0.0093, r < 0.17 (95% CL), and N eff = 3.86 ? 0.42. The SPT+WMAP data show a mild preference for low power in the CMB damping tail, and while this preference may be accommodated by models that have a negative spectral running, a high primordial helium abundance, or a high effective number of relativistic species, such models are disfavored by the abundance of low-redshift galaxy clusters.
Percutaneous coronary intervention (PCI) involving drug-eluting stents is increasingly used to treat complex coronary artery disease, although coronary-artery bypass grafting (CABG) has been the ...treatment of choice historically. Our trial compared PCI and CABG for treating patients with previously untreated three-vessel or left main coronary artery disease (or both).
We randomly assigned 1800 patients with three-vessel or left main coronary artery disease to undergo CABG or PCI (in a 1:1 ratio). For all these patients, the local cardiac surgeon and interventional cardiologist determined that equivalent anatomical revascularization could be achieved with either treatment. A noninferiority comparison of the two groups was performed for the primary end point--a major adverse cardiac or cerebrovascular event (i.e., death from any cause, stroke, myocardial infarction, or repeat revascularization) during the 12-month period after randomization. Patients for whom only one of the two treatment options would be beneficial, because of anatomical features or clinical conditions, were entered into a parallel, nested CABG or PCI registry.
Most of the preoperative characteristics were similar in the two groups. Rates of major adverse cardiac or cerebrovascular events at 12 months were significantly higher in the PCI group (17.8%, vs. 12.4% for CABG; P=0.002), in large part because of an increased rate of repeat revascularization (13.5% vs. 5.9%, P<0.001); as a result, the criterion for noninferiority was not met. At 12 months, the rates of death and myocardial infarction were similar between the two groups; stroke was significantly more likely to occur with CABG (2.2%, vs. 0.6% with PCI; P=0.003).
CABG remains the standard of care for patients with three-vessel or left main coronary artery disease, since the use of CABG, as compared with PCI, resulted in lower rates of the combined end point of major adverse cardiac or cerebrovascular events at 1 year. (ClinicalTrials.gov number, NCT00114972.)
Intracranial hemorrhage is a serious possible complication in patients with brain arteriovenous malformation (AVM). Several morphologic factors associated with hemorrhagic AVM presentation have been ...established, but their relevance for the risk of subsequent AVM hemorrhage remains unclear.
The authors analyzed follow-up data on 622 consecutive patients from the prospective Columbia AVM database, limited to the period between initial AVM diagnosis and the start of treatment (i.e., any endovascular, surgical, or radiation therapy). Univariate and multivariate logistic regression and Cox proportional hazard models were applied to analyze the effect of patient age, gender, AVM size, anatomic location, venous drainage pattern, and associated arterial aneurysms on the risk of intracranial hemorrhage at initial presentation and during follow-up.
The mean pretreatment follow-up was 829 days (median: 102 days), during which 39 (6%) patients experienced AVM hemorrhage. Increasing age (hazard ratio HR 1.05, 95% CI 1.03 to 1.08), initial hemorrhagic AVM presentation (HR 5.38, 95% CI 2.64 to 10.96), deep brain location (HR 3.25, 95% CI 1.30 to 8.16), and exclusive deep venous drainage (HR 3.25, 95% CI 1.01 to 5.67) were independent predictors of subsequent hemorrhage. Annual hemorrhage rates on follow-up ranged from 0.9% for patients without hemorrhagic AVM presentation, deep AVM location, or deep venous drainage to as high as 34.4% for those harboring all three risk factors.
Hemorrhagic arteriovenous malformation (AVM) presentation, increasing age, deep brain location, and exclusive deep venous drainage appear to be independent predictors for AVM hemorrhage during natural history follow-up. The risk of spontaneous hemorrhage may be low in AVMs without these risk factors.
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