Factors associated with intracerebral hemorrhage after thrombolytic therapy for ischemic stroke pooled analysis of placebo data from the Stroke-Acute Ischemic NXY Treatment (SAINT) I and SAINT II trials

<p><b>Background and Purpose:</b> A number of factors have been associated with postthrombolysis intracerebral hemorrhage, but these have varied across studies.</p> <p><b>Methods:</b> We examined patients with acute ischemic stroke treated with intravenous tissue plasminogen activator within 3 hours of symptom onset who were enrolled in the placebo arms of 2 trials (Stroke-Acute Ischemic NXY Treatment [SAINT] I and II Trials) of a putative neuroprotectant. Early CT changes were graded using the Alberta Stroke Program Early CT Score (ASPECTS). Post–tissue plasminogen activator symptomatic intracerebral hemorrhage was defined as a worsening in National Institutes of Health Stroke Scale of ≥4 points within 36 hours with evidence of hemorrhage on follow-up neuroimaging. Good clinical outcome was defined as a modified Rankin scale of 0 to 2 at 90 days.</p> <p><b>Results:</b> Symptomatic intracerebral hemorrhage occurred in 5.6% of 965 patients treated with tissue plasminogen activator. In multivariable analysis, symptomatic intracerebral hemorrhage was increased with baseline antiplatelet use (single antiplatelet: OR, 2.04, 95% CI, 1.07 to 3.87, P=0.03; double antiplatelet: OR, 9.29, 3.28 to 26.32, P<0.001), higher National Institutes of Health Stroke Scale score (OR, 1.09 per point, 1.03 to 1.15, P=0.002), and CT changes defined by ASPECTS (ASPECTS 8 to 9: OR, 2.26, 0.63 to 8.10, P=0.21; ASPECTS ≤7: OR, 5.63, 1.66 to 19.10, P=0.006). Higher National Institutes of Health Stroke Scale was associated with decreased odds of good clinical outcome (OR, 0.82 per point, 0.79 to 0.85, P<0.001). There was no relationship between baseline antiplatelet use or CT changes and clinical outcome.</p> <p><b>Conclusions:</b> Along with higher National Institutes of Health Stroke Scale and extensive early CT changes, baseline antiplatelet use (particularly double antiplatelet therapy) was associated with an increased risk of post–tissue plasminogen activator symptomatic intracerebral hemorrhage. Of these factors, only National Institutes of Health Stroke Scale was associated with clinical outcome.</p&gt

Stroke outcome related to initial volume status and diuretic use

Background: We hypothesized that stroke outcome is related to multiple baseline hydration-related factors including volume contracted state (VCS) and diuretic use. Methods: We analyzed a prospective cohort of subjects with ischemic stroke <24 hours of onset, enrolled in acute treatment trials within the Virtual International Stroke Trials Archive. A VCS was defined based on BUN-to-creatinine ratio. The primary endpoint was modified Rankin Scale (mRS) at 90 days. Primary analysis employed generalized ordinal logistic regression over the mRS range, adjusted for THRIVE score, onset-to-enrollment time, and thrombolytic usage. Results: Of 5971 eligible stroke patients, 42% were taking diuretics at the time of hospitalization and 44% were in a VCS. Patients with VCS were older, had more vascular risk factors, were more likely taking diuretics and had more severe strokes. Diuretic use was associated with both reduced chance of achieving a good functional outcome (OR 0.57;95%CI 0.52-0.63) and increased mortality at 90 days (OR 2.30;95%CI 2.04-2.61). VCS was associated with greater mortality 90 days post-stroke (OR 1.53;95%CI 1.33-1.76). There was no evidence of effect modification among the three exposures of VCS, diuretic use, or hypokalemia in relation to outcome. Conclusions: A VCS at the time of hospitalization was associated with more severe stroke and odds of death but not associated with worse functional outcome when accounting for relevant characteristics. Diuretic use and low serum potassium at the time of stroke onset were associated with worse outcome and may be worthy of further investigation

A maximum density rule for surfaces of quasicrystals

A rule due to Bravais of wide validity for crystals is that their surfaces correspond to the densest planes of atoms in the bulk of the material. Comparing a theoretical model of i-AlPdMn with experimental results, we find that this correspondence breaks down and that surfaces parallel to the densest planes in the bulk are not the most stable, i.e. they are not so-called bulk terminations. The correspondence can be restored by recognizing that there is a contribution to the surface not just from one geometrical plane but from a layer of stacked atoms, possibly containing more than one plane. We find that not only does the stability of high-symmetry surfaces match the density of the corresponding layer-like bulk terminations but the exact spacings between surface terraces and their degree of pittedness may be determined by a simple analysis of the density of layers predicted by the bulk geometric model.Comment: 8 pages of ps-file, 3 Figs (jpg

Hamiltonian Description of Composite Fermions: Magnetoexciton Dispersions

A microscopic Hamiltonian theory of the FQHE, developed by Shankar and myself based on the fermionic Chern-Simons approach, has recently been quite successful in calculating gaps in Fractional Quantum Hall states, and in predicting approximate scaling relations between the gaps of different fractions. I now apply this formalism towards computing magnetoexciton dispersions (including spin-flip dispersions) in the $\nu=1/3$, 2/5, and 3/7 gapped fractions, and find approximate agreement with numerical results. I also analyse the evolution of these dispersions with increasing sample thickness, modelled by a potential soft at high momenta. New results are obtained for instabilities as a function of thickness for 2/5 and 3/7, and it is shown that the spin-polarized 2/5 state, in contrast to the spin-polarized 1/3 state, cannot be described as a simple quantum ferromagnet.Comment: 18 pages, 18 encapsulated ps figure

Early in-hospital exposure to statins and outcome after intracerebral haemorrhage - Results from the Virtual International Stroke Trials Archive

Introduction Recent data suggest that statin use after intracerebral haemorrhage might be beneficial. However, data on the effects of early in-hospital statin exposure are lacking. Therefore, we sought to assess whether (1) early statin exposure during the acute phase after intracerebral haemorrhage and (2) early continuation of prevalent statin use are associated with favourable functional outcome. Patients and methods Data were obtained from the Virtual International Stroke Trials Archive. Patients were categorised according to use patterns of statins during this early in-hospital phase (continuation, discontinuation or new initiation of statins). Univariate and multivariable analyses were conducted to explore the association between early statin exposure and functional outcome. Results A total of 919 patients were included in the analysis. Early in-hospital statin exposure (n = 89, 9.7%) was associated with better functional outcome (modified Rankin Scale <= 3) compared with 790 patients without statin exposure before or early after the event (66% versus 47%, adjusted OR 2.1, 95% confidence interval 1.3-3.6). Compared with patients without exposure to statins before and early after the event, early continuation of statin therapy (n = 57) was associated with favourable functional outcome (adjusted odds ratio 2.6, 95% confidence interval 1.3-5.2). The association between early continuation of statins and outcome remained robust in sensitivity analyses restricted to patients able to take oral medication within 72 h and one-week survivors. Discussion It is possible that part of the observed associations are not due to a protective effect of statins but are confounded by indication bias. Conclusion Statin exposure and continuation of prevalent statin therapy early after intracerebral haemorrhage are associated with favourable functional outcome after 90 days

Brane Inflation, Solitons and Cosmological Solutions: I

In this paper we study various cosmological solutions for a D3/D7 system directly from M-theory with fluxes and M2-branes. In M-theory, these solutions exist only if we incorporate higher derivative corrections from the curvatures as well as G-fluxes. We take these corrections into account and study a number of toy cosmologies, including one with a novel background for the D3/D7 system whose supergravity solution can be completely determined. This new background preserves all the good properties of the original model and opens up avenues to investigate cosmological effects from wrapped branes and brane-antibrane annihilation, to name a few. We also discuss in some detail semilocal defects with higher global symmetries, for example exceptional ones, that could occur in a slightly different regime of our D3/D7 model. We show that the D3/D7 system does have the required ingredients to realise these configurations as non-topological solitons of the theory. These constructions also allow us to give a physical meaning to the existence of certain underlying homogeneous quaternionic Kahler manifolds.Comment: Harvmac, 115 pages, 9 .eps figures; v2: typos corrected, references added and the last section expanded; v3: Few minor typos corrected and references added. Final version to appear in JHE

Early- Onset Stroke and Vasculopathy Associated with Mutations in ADA2

Adenosine deaminase 2 (ADA2) is an enzyme involved in purine metabolism and a growth factor that influences the development of endothelial cells and leukocytes. This study shows that defects in ADA2 cause recurrent fevers, vascular pathologic features, and mild immunodeficiency. Patients with autoinflammatory disease sometimes present with clinical findings that encompass multiple organ systems.(1) Three unrelated children presented to the National Institutes of Health (NIH) Clinical Center with intermittent fevers, recurrent lacunar strokes, elevated levels of acute-phase reactants, livedoid rash, hepatosplenomegaly, and hypogammaglobulinemia. Collectively, these findings do not easily fit with any of the known inherited autoinflammatory diseases. Hereditary or acquired vascular disorders can have protean manifestations yet be caused by mutations in a single gene. Diseases such as the Aicardi-Goutieres syndrome,(2),(3) polypoidal choroidal vasculopathy,(4) sickle cell anemia,(5) livedoid vasculopathy,(6) and the small-vessel vasculitides(7),(8) are examples of systemic ...</p

Dissipative transport in quantum Hall ferromagnets by spin-wave scattering

We report on a study of the effect upon electrical transport of spin-wave scattering from charged quasiparticles in nu = 1 quantum Hall ferromagnets, including both Heisenberg (single layer) and easy-plane (bilayer) cases. We derive a quantum Langevin equation to describe the resulting diffusive motion of the charged particle and use this to calculate the contribution to low-temperature conductivity from a density of charged particles. This conductivity has a power-law dependence upon temperature. The contribution is small at low temperatures increasing to a large value at relatively modest temperatures. We comment upon high-temperature transport and upon the contribution of scattering to the width of the zero bias peak in tunneling conductivity

Potential Embolic Sources and Outcomes in Embolic Stroke of Undetermined Source in the NAVIGATE-ESUS Trial

Background and Purpose - Emboli in embolic stroke of undetermined source (ESUS) may originate from various potential embolic sources (PES), some of which may respond better to anticoagulation, whereas others to antiplatelets. We analyzed whether rivaroxaban is associated with reduction of recurrent stroke compared with aspirin in patients with ESUS across different PES and by number of PES. Methods - We assessed the presence/absence of each PES (atrial cardiopathy, atrial fibrillation, arterial atherosclerosis, left ventricular dysfunction, cardiac valvulopathy, patent foramen ovale, cancer) in NAVIGATE-ESUS (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source) participants. Prevalence of each PES, as well as treatment effect and risk of event for each PES were determined. Results by number of PES were also determined. The outcomes were ischemic stroke, all-cause mortality, cardiovascular mortality, and myocardial infarction. Results - In 7213 patients (38% women, mean age 67years) followed for a median of 11 months, the 3 most prevalent PES were atrial cardiopathy (37%), left ventricular disease (36%), and arterial atherosclerosis (29%). Forty-one percent of all patients had multiple PES, with 15% having ≥3 PES. None or a single PES was present in 23% and 36%, respectively. Recurrent ischemic stroke risk was similar for rivaroxaban- and aspirin-assigned patients for each PES, except for those with cardiac valvular disease which was marginally higher in rivaroxaban-assigned patients (hazard ratio, 1.8 [95% CI, 1.0-3.0]). All-cause mortality risks were similar across treatment groups for each PES while too few myocardial infarctions and cardiovascular deaths occurred for meaningful assessment. Increasing number of PES was not associated with increased stroke recurrence nor all-cause mortality, and outcomes did not vary between rivaroxaban- and aspirin-assigned patients by number of PES. Conclusions - A large proportion of patients with ESUS had multiple PES which could explain the neutral results of NAVIGATE-ESUS. Recurrence rates between rivaroxaban- and aspirin-assigned patients were similar across the spectrum of PES. Registration - URL: https://www.clinicaltrials.gov; Unique identifier: NCT02313909. © 2020 Lippincott Williams and Wilkins. All rights reserved