Safety of intravenous thrombolysis for acute ischemic stroke in patients receiving antiplatelet therapy at stroke onset

<p><b>Background and Purpose:</b> Antiplatelets (APs) may increase the risk of symptomatic intracerebral hemorrhage (ICH) following intravenous thrombolysis after ischemic stroke.</p> <p><b>Methods:</b> We assessed the safety of thrombolysis under APs in 11 865 patients compliant with the European license criteria and recorded between 2002 and 2007 in the Safe Implementation of Treatments in Stroke (SITS) International Stroke Thrombolysis Register (SITS-ISTR). Outcome measures of univariable and multivariable analyses included symptomatic ICH (SICH) per SITS Monitoring Study (SITS-MOST [deterioration in National Institutes of Health Stroke Scale >= 4 plus ICH type 2 within 24 hours]), per European Cooperative Acute Stroke Study II (ECASS II [deterioration in National Institutes of Health Stroke Scale >= 4 plus any ICH]), functional outcome at 3 months and mortality.</p> <p><b>Results:</b> A total of 3782 (31.9%) patients had received 1 or 2 AP drugs at baseline: 3016 (25.4%) acetylsalicylic acid (ASA), 243 (2.0%) clopidogrel, 175 (1.5%) ASA and dipyridamole, 151 (1.3%) ASA and clopidogrel, and 197 (1.7%) others. Patients receiving APs were 5 years older and had more risk factors than AP nave patients. Incidences of SICH per SITS-MOST (ECASS II respectively) were as follows: 1.1% (4.1%) AP naive, 2.5% (6.2%) any AP, 2.5% (5.9%) ASA, 1.7% (4.2%) clopidogrel, 2.3% (5.9%) ASA and dipyridamole, and 4.1% (13.4%) ASA and clopidogrel. In multivariable analyses, the combination of ASA and clopidogrel was associated with increased risk for SICH per ECASS II (odds ratio, 2.11; 95% CI, 1.29 to 3.45; P = 0.003). However, we found no significant increase in the risk for mortality or poor functional outcome, irrespective of the AP subgroup or SICH definition.</p> <p><b>Conclusion:</b> The absolute excess of SICH of 1.4% (2.1%) in the pooled AP group is small compared with the benefit of thrombolysis seen in randomized trials. Although caution is warranted in patients receiving the combination of ASA and clopidogrel, AP treatment should not be considered a contraindication to thrombolysis.</p&gt

Mutations in CYB561 Causing a Novel Orthostatic Hypotension Syndrome

Rationale: Orthostatic hypotension is a common clinical problem, but the underlying mechanisms have not been fully delineated. Objective: We describe two families, with four patients in total, suffering from severe life-threatening orthostatic hypotension due to a novel cause. Methods and Results: As in dopamine β-hydroxylase deficiency (DβH), concentrations of norepinephrine and epinephrine in the patients were very low. Plasma DβH activity, however, was normal and the DBH gene had no mutations. Molecular genetic analysis was performed to determine the underlying genetic cause. Homozygosity mapping and exome and Sanger sequencing revealed pathogenic homozygous mutations in the gene encoding cytochrome b561 (CYB561); a missense variant c.262G>A, p.Gly88Arg in exon 3 in the Dutch family and a nonsense mutation (c.131G>A, p.Trp44*) in exon 2 in the American family. Expression of CYB561 was investigated using RNA from different human adult and fetal tissues, transcription of RNA into cDNA and real-time quantitative polymerase chain reaction. The CYB561 gene was found to be expressed in many human tissues, in particular the brain. The CYB561 protein defect leads to a shortage of ascorbate inside the catecholamine secretory vesicles leading to a functional DβH deficiency. The concentration of the catecholamines and downstream metabolites was measured in brain and adrenal tissue of six CYB561 knockout mice (reporter-tagged deletion allele (post-Cre), genetic background C57BL/6NTac). The concentration of norepinephrine and normetanephrine was decreased in whole brain homogenates of the CYB561(-/-) mice compared to wild type mice (p<0.01) and the concentration of normetanephrine and metanephrine was decreased in adrenal glands (p<0.01), recapitulating the clinical phenotype. The patients responded favorably to treatment with L-dihydroxyphenylserine, which can be converted directly to norepinephrine. Conclusions: This study is the first to implicate cytochrome b561 in disease by showing that pathogenic mutations in CYB561 cause an as yet unknown disease in neurotransmitter metabolism causing orthostatic hypotension. as yet unknown disease in neurotransmitter metabolism causing orthostatic hypotension

Spin-Momentum Correlations in Quasi-Elastic Electron Scattering from Deuterium

We report on a measurement of spin-momentum correlations in quasi-elastic scattering of longitudinally polarized electrons with an energy of 720 MeV from vector-polarized deuterium. The spin correlation parameter $A^V_{ed}$ was measured for the $^2 \vec{\rm H}(\vec e,e^\prime p)n$ reaction for missing momenta up to 350 MeV/$c$ at a four-momentum transfer squared of 0.21 (GeV/c)$^2$. The data give detailed information about the spin structure of the deuteron, and are in good agreement with the predictions of microscopic calculations based on realistic nucleon-nucleon potentials and including various spin-dependent reaction mechanism effects. The experiment demonstrates in a most direct manner the effects of the D-state in the deuteron ground-state wave function and shows the importance of isobar configurations for this reaction.Comment: 4 pages, 3 figures, submitted to Phys. Rev. Lett. for publicatio

The Diagnostic Value of Near-Infrared Spectroscopy to Predict Delayed Cerebral Ischemia and Unfavorable Outcome After Subarachnoid Hemorrhage

OBJECTIVE: Near-infrared spectroscopy (NIRS) is a non-invasive tool to monitor cerebral regional oxygen saturation. Impairment of microvascular circulation with subsequent cerebral hypoxia during delayed cerebral ischemia (DCI) is associated with poor functional outcome after subarachnoid hemorrhage (SAH). Therefore, NIRS could be useful to predict the risk for DCI and functional outcome. However, only limited data is available on NIRS regional cerebral tissue oxygen saturation (rSO2) distribution in SAH. The aim of this study was to compare the distribution of NIRS rSO2 values in non-traumatic SAH patients with the occurrence of DCI and functional outcome at two months. In addition, the predictive value of NIRS rSO2 was compared with the previously validated SAFIRE grade (derived from Size of the aneurysm, Age, FIsher grade, world federation of neurosurgical societies after REsuscitation).METHODS: In this study, the rSO2 distribution of patient with and without DCI after SAH are compared. The optimal cutoff points to predict DCI and outcome are assessed, and its predictive value is compared to the SAFIRE grade.RESULTS: Out of 41 patients, 12 developed DCI, and 9 had unfavorable outcome at 60 days. Prediction of DCI with NIRS had an area under the curve (AUC) of 0.77 (95%CI 0.62-0.92; p=0.0028) with an optimal cutoff point of 65% (sensitivity 1.00; specificity 0.45). Prediction of favorable outcome with NIRS had an AUC of 0.86 (95%CI 0.74-0.98; p=0.0003) with an optimal cutoff point of 63% (sensitivity 1.00; specificity 0.63). Regression analysis showed that NIRS rSO2 score is complementary to the SAFIRE grade.CONCLUSION: NIRS rSO2 monitoring in patients with SAH may improve prediction of DCI and clinical outcome after SAH.</p

The predictive value of the CTA Vasospasm Score on delayed cerebral ischaemia and functional outcome after aneurysmal subarachnoid hemorrhage

Background and purpose: Delayed cerebral ischaemia (DCI) is a severe complication of aneurysmal subarachnoid hemorrhage that can significantly impact clinical outcome. Cerebral vasospasm is part of the pathophysiology of DCI and therefore a computed tomography angiography (CTA) Vasospasm Score was developed and an exploration was carried out of whether this score predicts DCI and subsequent poor outcome after aneurysmal subarachnoid hemorrhage. Methods: The CTA Vasospasm Score sums the degree of angiographic cerebral vasospasm of 17 intradural arterial segments. The score ranges from 0 to 34 with a higher score reflecting more severe vasospasm. Outcome measures were cerebral infarction due to DCI (CI-DCI), radiological and clinical DCI, and unfavorable functional outcome defined as a modified Rankin Scale >2 at 6 months. Receiver operating characteristic analyses were used to assess predictive value and to determine optimal cut-off scores. Inter-rater reliability was evaluated by Cohen's kappa coefficient. Results: This study included 59 patients. CI-DCI occurred in eight patients (14%), DCI in 14 patients (24%) and unfavorable outcome in 12 patients (20%). Median CTA Vasospasm Scores were higher in patients with (CI-)DCI and poor outcome. Receiver operating characteristic analysis revealed the highest area under the curve on day 5: CI-DCI 0.89 (95% confidence interval [CI] 0.79–0.99), DCI 0.68 (95% CI 0.50–0.87) and functional outcome 0.74 (95% CI 0.57–0.91). Cohen's kappa between the two raters was moderate to substantial (0.57–0.63). Conclusions: This study demonstrates that the CTA Vasospasm Score on day 5 can reliably identify patients with a high risk of developing (CI-)DCI and unfavorable outcome

The Diagnostic Value of Near-Infrared Spectroscopy to Predict Delayed Cerebral Ischemia and Unfavorable Outcome After Subarachnoid Hemorrhage

OBJECTIVE: Near-infrared spectroscopy (NIRS) is a non-invasive tool to monitor cerebral regional oxygen saturation. Impairment of microvascular circulation with subsequent cerebral hypoxia during delayed cerebral ischemia (DCI) is associated with poor functional outcome after subarachnoid hemorrhage (SAH). Therefore, NIRS could be useful to predict the risk for DCI and functional outcome. However, only limited data is available on NIRS regional cerebral tissue oxygen saturation (rSO2) distribution in SAH. The aim of this study was to compare the distribution of NIRS rSO2 values in non-traumatic SAH patients with the occurrence of DCI and functional outcome at two months. In addition, the predictive value of NIRS rSO2 was compared with the previously validated SAFIRE grade (derived from Size of the aneurysm, Age, FIsher grade, world federation of neurosurgical societies after REsuscitation).METHODS: In this study, the rSO2 distribution of patient with and without DCI after SAH are compared. The optimal cutoff points to predict DCI and outcome are assessed, and its predictive value is compared to the SAFIRE grade.RESULTS: Out of 41 patients, 12 developed DCI, and 9 had unfavorable outcome at 60 days. Prediction of DCI with NIRS had an area under the curve (AUC) of 0.77 (95%CI 0.62-0.92; p=0.0028) with an optimal cutoff point of 65% (sensitivity 1.00; specificity 0.45). Prediction of favorable outcome with NIRS had an AUC of 0.86 (95%CI 0.74-0.98; p=0.0003) with an optimal cutoff point of 63% (sensitivity 1.00; specificity 0.63). Regression analysis showed that NIRS rSO2 score is complementary to the SAFIRE grade.CONCLUSION: NIRS rSO2 monitoring in patients with SAH may improve prediction of DCI and clinical outcome after SAH.</p

The Diagnostic Value of Near-Infrared Spectroscopy to Predict Delayed Cerebral Ischemia and Unfavorable Outcome After Subarachnoid Hemorrhage

OBJECTIVE: Near-infrared spectroscopy (NIRS) is a non-invasive tool to monitor cerebral regional oxygen saturation. Impairment of microvascular circulation with subsequent cerebral hypoxia during delayed cerebral ischemia (DCI) is associated with poor functional outcome after subarachnoid hemorrhage (SAH). Therefore, NIRS could be useful to predict the risk for DCI and functional outcome. However, only limited data is available on NIRS regional cerebral tissue oxygen saturation (rSO2) distribution in SAH. The aim of this study was to compare the distribution of NIRS rSO2 values in non-traumatic SAH patients with the occurrence of DCI and functional outcome at two months. In addition, the predictive value of NIRS rSO2 was compared with the previously validated SAFIRE grade (derived from Size of the aneurysm, Age, FIsher grade, world federation of neurosurgical societies after REsuscitation).METHODS: In this study, the rSO2 distribution of patient with and without DCI after SAH are compared. The optimal cutoff points to predict DCI and outcome are assessed, and its predictive value is compared to the SAFIRE grade.RESULTS: Out of 41 patients, 12 developed DCI, and 9 had unfavorable outcome at 60 days. Prediction of DCI with NIRS had an area under the curve (AUC) of 0.77 (95%CI 0.62-0.92; p=0.0028) with an optimal cutoff point of 65% (sensitivity 1.00; specificity 0.45). Prediction of favorable outcome with NIRS had an AUC of 0.86 (95%CI 0.74-0.98; p=0.0003) with an optimal cutoff point of 63% (sensitivity 1.00; specificity 0.63). Regression analysis showed that NIRS rSO2 score is complementary to the SAFIRE grade.CONCLUSION: NIRS rSO2 monitoring in patients with SAH may improve prediction of DCI and clinical outcome after SAH.</p

Standalone vertex finding in the ATLAS muon spectrometer

A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at √s = 7 TeV collected with the ATLAS detector at the LHC during 2011

Measurements of Higgs boson production and couplings in diboson final states with the ATLAS detector at the LHC

Measurements are presented of production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs, H →γ γ, H → Z Z∗ →4l and H →W W∗ →lνlν. The results are based on the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV, corresponding to an integrated luminosity of about 25 fb−1. Evidence for Higgs boson production through vector-boson fusion is reported. Results of combined fits probing Higgs boson couplings to fermions and bosons, as well as anomalous contributions to loop-induced production and decay modes, are presented. All measurements are consistent with expectations for the Standard Model Higgs boson

Measurement of the top quark pair cross section with ATLAS in pp collisions at √s=7 TeV using final states with an electron or a muon and a hadronically decaying τ lepton

A measurement of the cross section of top quark pair production in proton-proton collisions recorded with the ATLAS detector at the Large Hadron Collider at a centre-of-mass energy of 7 TeV is reported. The data sample used corresponds to an integrated luminosity of 2.05 fb -1. Events with an isolated electron or muon and a τ lepton decaying hadronically are used. In addition, a large missing transverse momentum and two or more energetic jets are required. At least one of the jets must be identified as originating from a b quark. The measured cross section, σtt-=186±13(stat.)±20(syst.)±7(lumi.) pb, is in good agreement with the Standard Model prediction