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e excellent outcome (definition 1 adjusted odds ratio, 0.55 [95% CI, 0.31-0.99]; definition 2 adjusted odds ratio, 0.62 [95% CI, 0.31-1.25]).

MeVO patients with discrepant infarcts are common, and they are associated with more severe deficits and poor outcomes.

MeVO patients with discrepant infarcts are common, and they are associated with more severe deficits and poor outcomes.

Coronavirus disease 2019 (COVID-19) evolved quickly into a global pandemic with myriad systemic complications, including stroke. We report the largest case series to date of cerebrovascular complications of COVID-19 and compare with stroke patients without infection.

Retrospective case series of COVID-19 patients with imaging-confirmed stroke, treated at 11 hospitals in New York, between March 14 and April 26, 2020. Demographic, clinical, laboratory, imaging, and outcome data were collected, and cases were compared with date-matched controls without COVID-19 from 1 year prior.

Eighty-six COVID-19-positive stroke cases were identified (mean age, 67.4 years; 44.2% women). Ischemic stroke (83.7%) and nonfocal neurological presentations (67.4%) predominated, commonly involving multivascular distributions (45.8%) with associated hemorrhage (20.8%). Compared with controls (n=499), COVID-19 was associated with in-hospital stroke onset (47.7% versus 5.0%;

<0.001), mortality (29.1% versus 9.0%;

<0.001), and Black/multiracial race (58.1% versus 36.9%;

=0.001). COVID-19 was the strongest independent risk factor for in-hospital stroke (odds ratio, 20.9 [95% CI, 10.4-42.2];

<0.001), whereas COVID-19, older age, and intracranial hemorrhage independently predicted mortality.

COVID-19 is an independent risk factor for stroke in hospitalized patients and mortality, and stroke presentations are frequently atypical.

COVID-19 is an independent risk factor for stroke in hospitalized patients and mortality, and stroke presentations are frequently atypical.

Enlarged perivascular spaces (EPVS) have been associated with aging, increased stroke risk, decreased cognitive function, and vascular dementia. However, the relationship of EPVS with age-related neuropathologies is not well understood. Therefore, the purpose of this study was to assess the neuropathologic correlates of EPVS in a large community-based cohort of older adults. The cognitive correlates of EPVS over and beyond those of other pathologies were also assessed.

This study included 654 older deceased and autopsied participants of 3 longitudinal community-based studies of aging that had available data on cognition, ex vivo brain magnetic resonance imaging, and detailed neuropathologic examination. EPVS seen on ex vivo magnetic resonance imaging were histologically validated. Experienced observers rated EPVS burden in ex vivo magnetic resonance imaging using a semiquantitative 4-level scale. Elastic-net regularized ordinal logistic regression was used to investigate associations of EPVS burden with aogies, extending recent findings in animal studies implicating diabetes mellitus in impairment of the glymphatic system. Finally, EPVS burden may reflect additional brain tissue injury that may contribute to cognitive decline, not captured with traditional neuropathologic measures.

EPVS and infarcts may share similar neurobiological pathways regardless of dementia status. EPVS burden is linked to diabetes mellitus independently of neuropathologies, extending recent findings in animal studies implicating diabetes mellitus in impairment of the glymphatic system. Finally, EPVS burden may reflect additional brain tissue injury that may contribute to cognitive decline, not captured with traditional neuropathologic measures.

In large artery occlusion stroke, both intravenous (IV) tPA (tissue-type plasminogen activator) and endovascular stroke treatment (EST) are standard-of-care. It is unknown how often tPA causes distal embolization, in which a procedurally accessible large artery occlusion is converted to a more distal and potentially inaccessible occlusion.

We analyzed data from a decentralized stroke telemedicine program in an integrated healthcare delivery system covering 21 hospitals, with 2 high-volume EST centers. We captured all cases sent for EST and examined the relationship between IV tPA administration and the rate of distal embolization, the rate of target recanalization (modified Treatment in Cerebral Infarction scale 2b/3), clinical improvement before EST, and short-term and long-term clinical outcomes.

Distal embolization before EST was quite common (63/314 [20.1%]) and occurred more often after IV tPA before EST (57/229 [24.9%]) than among those not receiving IV tPA (6/85 [7.1%];

<0.001). Distal emboltal embolization and improved long-term clinical outcome, there is a need for prospective clinical trials testing the net benefit or harm of IV tPA before EST.

IV tPA administration before EST for large artery occlusion is associated with distal embolization, which in turn may reduce the chance that EST can be attempted and recanalization achieved. At the same time, some IV tPA-treated patients show symptomatic improvement and complete recanalization. Because IV tPA is associated with both distal embolization and improved long-term clinical outcome, there is a need for prospective clinical trials testing the net benefit or harm of IV tPA before EST.A physiologically based pharmacokinetic (PBPK) model for di-isononyl phthalate (DiNP) was developed by adapting the existing models for di(2-ethylhexyl) phthalate (DEHP) and di-butylphthalate (DBP). Both pregnant rat and human time-course plasma and urine data were used to address the hydrolysis of DiNP in intestinal tract, plasma, and liver as well as hepatic oxidative metabolism and conjugation of the monoester and primary oxidative metabolites. Data in both rats and humans were available to inform the uptake and disposition of mono-isononyl phthalate (MiNP) as well as the three primary oxidative metabolites including hydroxy (7-OH)-, oxo (7-OXO)-, and carboxy (7-COX)-monoisononyl phthalate in plasma and urine. The DiNP model was reliable over a wide range of exposure levels in the pregnant rat as well as the two low exposure levels in humans including capturing the nonlinear behavior in the pregnant rat after repeated 750 mg/kg/day dosing. EPZ015666 order The presented DiNP PBPK model in pregnant rat and human, based upon an extensive kinetic dataset in both species, may provide a basis for assessing human equivalent exposures based upon either rodent or in vitro points of departure.

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