Optimal Angiographic Goal and Number of Passes for Octogenarians Undergoing Endovascular Stroke Thrombectomy.

BACKGROUND: The optimal recanalization goal and number of endovascular thrombectomy (EVT) passes for elderly patients with large vessel occlusion strokes is unclear. METHODS: Consecutive patients 80 years or older undergoing EVT were identified from 2016 to 2022 at a single center. Clinical information, procedural details, and modified treatment in cerebral ischemia (mTICI) scores were collected. Primary outcome was modified Rankin scale (mRS) at 90 days. Bivariate and multivariable analyses were conducted to assess associations between mTICI scores, EVT passes, and 90-day outcomes. RESULTS: One hundred twenty-six patients were identified. At 90 days, mTICI 2b recanalization resulted in high rates of poor outcomes (8.7% functional independence and 60.9% mortality) not significantly different from mTICI 0, 1 or 2a (median mRS 6 vs. 6, P = 0.61). Complete recanalization (mTICI 2c or 3) led to significantly better mRS outcomes at 90 days compared to mTICI 2b (median mRS 4 vs. 6, adjusted P = 0.038), with 26.8% functional independence and 37.8% mortality. In multivariable analysis, complete recanalization was significantly associated with better 90-day outcomes than mTICI 2b or lower recanalization (odds ratio 4.24 [95% Confidence interval 1.46-12.3]; P = 0.002), while the number of passes was not independently associated with worse outcomes (P = 0.98). CONCLUSIONS: For octogenarians, mTICI 2b recanalization yields limited clinical benefit and results in poor 90-day outcomes. In contrast, complete recanalization is independently associated with significantly better outcomes. Thus, once the decision is made to pursue EVT in the elderly, mTICI 2c or better recanalization should be the angiographic goal. Providers should not withhold thrombectomy passes based on age alone.

The BAND score: A simple model for upfront prediction of poor outcomes despite successful stroke thrombectomy.

BACKGROUND: While endovascular thrombectomy (EVT) is beneficial for patients with acute large vessel occlusion ischemic strokes, a significant portion of patients still do poorly despite successful recanalization. Identifying patients at high risk for poor outcomes can be helpful for future clinical trial design and optimizing acute stroke triage. METHODS: Consecutive EVT patients were identified from 2016 to 2021 at a Comprehensive Stroke Center, and clinical information was recorded. Poor outcome was defined as a 90-day modified Rankin Scale (mRS) of 4 or greater despite achieving a modified thrombolysis in cerebral infarction (mTICI) score of 2b or greater. Multivariable regression analyses were used to identify risk factors for poor outcomes, and a scoring system was constructed. RESULTS: 483 patients with successful recanalization were identified. From a randomly selected training cohort (n = 357), the 10-point BAND score was constructed from independent risk factors for poor outcomes: baseline disability (1 point: baseline mRS ≥ 2), age (1 point: 60-69 years, 2 points: 70-79 years, 3 points: 80-84 years, 4 points: 85 years or older), NIHSS (2 points: 13-17, 3 points: 18-22, and 4 points: ≥ 23), and delay from last known normal (1 point: ≥ 6 h). The BAND score was significantly associated with rates of poor outcomes (p < 0.001), and it achieved an area under the receiver-operating characteristic curve (AUC) of 0.80 (95 %CI 0.76-0.85) in our training cohort and 0.78 (95 %CI 0.70-0.86) in our validation cohort (n = 126). Overall, the BAND score had a significantly higher AUC value than the widely validated THRIVE score and the THRIVE-EVT calculation (p = 0.001 and 0.029, respectively). Among patients with high BAND scores (7 or higher), 88.2 % had poor outcomes. CONCLUSION: The BAND score is a simple tool to predict poor outcomes despite successful recanalization. Future studies are needed to confirm the BAND score's external validity.

Peri-procedural decrease in hemoglobin following mechanical thrombectomy for ischemic stroke.

BACKGROUND: Peri-procedural blood loss and hemodilution occur in patients undergoing mechanical thrombectomy (MT) for ischemic stroke; however, its relationships with thrombectomy passes, procedure times, and clinical outcomes are unknown. METHODS: Consecutive patients undergoing MT for anterior circulation large-vessel occlusion ischemic strokes were identified at a Comprehensive Stroke Center. Clinical information, modified treatment in cerebral ischemia (mTICI) scores, and modified Rankin Scores (mRS) at 90 days were prospectively collected from 2012 to 2021. Hemoglobin measurements before and after MTs were collected retrospectively via chart review, and changes were quantified. Patients with new-onset severe anemia (defined as post-MT hemoglobin less than 10g/dL) were identified. Modified Rankin scale (mRS) at 90 days was used to measure clinical outcomes. RESULTS: Four-hundred and forty-five patients were identified. Hemoglobin decreased 1.27 ± 1.05 g/dL after MT on average. Greater number of thrombectomy passes and longer procedure times were associated with larger decreases in hemoglobin (p < 0.001 and p = 0.002, respectively). 11.5% (51 of 445) of patients had new-onset severe anemia, and this incidence was significantly higher with more thrombectomy passes (6.4% for one pass, 11.9% for two passes, and 17.4% for three or more passes; p = 0.010). In multivariable analyses, new-onset severe anemia was associated with significantly higher odds of 90-day poor outcomes (mRS 3-6, OR 2.70 [95%CI 1.12-6.51], p = 0.027) and death (OR 2.73 [95%CI 1.06-7.04], p = 0.037) compared to mild post-MT anemia. CONCLUSIONS: More thrombectomy passes and longer procedure times were significantly associated with larger peri-procedural decreases in hemoglobin. Patients with new-onset hemoglobin less than 10 g/dL are at risk of poor outcomes.

Prediction of blood pressure variability during thrombectomy using supervised machine learning and outcomes of patients with ischemic stroke from large vessel occlusion.

Mechanical thrombectomy (MT) is the standard of care for patients with acute ischemic stroke from large vessel occlusion (AIS-LVO). The association of blood pressure variability (BPV) during MT and outcomes are unknown. We leveraged a supervised machine learning algorithm to predict patient characteristics that are associated with BPV indices. We performed a retrospective review of our comprehensive stroke center's registry of all adult patients undergoing MT between 01/01/2016 and 12/31/2019. The primary outcome was poor functional independence, defined as 90-day modified Rankin Scale (mRS) ≥ 3. We used probit analysis and multivariate logistic regressions to evaluate the association of patients' clinical factors and outcomes. We applied a machine learning algorithm (random forest, RF) to determine predictive factors for the different BPV indices during MT. Evaluation was performed with root-mean-square error (RMSE) and normalized-RMSE (nRMSE) metrics. We analyzed 375 patients with mean age (± standard deviation [SD]) of 65 (15) years. There were 234 (62%) patients with mRS ≥ 3. Univariate probit analysis demonstrated that BPV during MT was associated with poor functional independence. Multivariable logistic regression showed that age, admission National Institutes of Health Stroke Scale (NIHSS), mechanical ventilation, and thrombolysis in cerebral infarction (TICI) score (OR 0.42, 95% CI 0.17-0.98, P = 0.044) were significantly associated with outcome. RF analysis identified that the interval from last-known-well time-to-groin puncture, age, and mechanical ventilation were among important factors significantly associated with BPV. BPV during MT was associated with functional outcome in univariate probit analysis but not in multivariable regression analysis, however, NIHSS and TICI score were. RF algorithm identified risk factors influencing patients' BPV during MT. While awaiting further studies' results, clinicians should still monitor and avoid high BPV during thrombectomy while triaging AIS-LVO candidates quickly to MT.

Sc-HOPO: A Potential Construct for Use in Radioscandium-Based Radiopharmaceuticals.

Three isotopes of scandium─43Sc, 44Sc, and 47Sc─have attracted increasing attention as potential candidates for use in imaging and therapy, respectively, as well as for possible theranostic use as an elementally matched pair. Here, we present the octadentate chelator 3,4,3-(LI-1,2-HOPO) (or HOPO), an effective chelator for hard cations, as a potential ligand for use in radioscandium constructs with simple radiolabeling under mild conditions. HOPO forms a 1:1 Sc-HOPO complex that was fully characterized, both experimentally and theoretically. [47Sc]Sc-HOPO exhibited good stability in chemical and biological challenges over 7 days. In healthy mice, [43,47Sc]Sc-HOPO cleared the body rapidly with no signs of demetalation. HOPO is a strong candidate for use in radioscandium-based radiopharmaceuticals.

Mildly elevated INR is associated with worse outcomes following mechanical thrombectomy for acute ischemic stroke.

BACKGROUND: Elevated International Normalized Ratio (INR) is a marker of coagulopathy, but its impact on outcomes following mechanical thrombectomy (MT) in patients with stroke is unclear. This study investigates the impact of mild INR elevations on clinical outcomes following MT. METHODS: In this retrospective cohort study, consecutive patients with stroke treated with MT were identified from 2015 to 2020 at a Comprehensive Stroke Center. Demographic information, past medical history, INR, National Institutes of Health Stroke Scale score, use of tissue plasminogen activator, and last known normal to arteriotomy time were recorded. Outcome measures included modified Thrombolysis in Cerebral Infarction (mTICI) score, modified Rankin Scale (mRS) score at 90 days, and intracerebral hemorrhage (ICH). Patients were divided into two groups: normal INR (0.8-1.1) and mildly elevated INR (1.2-1.7). RESULTS: A total of 489 patients were included for analysis, of which 349 had normal INR and 140 had mildly elevated INR. After multivariable adjustments, mildly elevated INR was associated with lower odds of excellent outcomes (mRS 0-1, OR 0.24, p=0.009), lower odds of functional independence (mRS 0-2, OR 0.38, p=0.038), and higher odds of 90-day mortality (OR 3.45, p=0.018). Elevated INR was not associated with a higher likelihood of ICH, and there were no differences in rates of HI1, HI2, PH1, or PH2 hemorrhagic transformations; however, elevated INR was associated with significantly higher odds of 90-day mortality in patients with ICH (OR 6.22, p=0.024). This effect size was larger than in patients without ICH (OR 3.38, p<0.001). CONCLUSION: In patients with stroke treated with MT, mildly elevated INR is associated with worse clinical outcomes after recanalization and may worsen the mortality risk of hemorrhagic transformations.

Black-white Differences in Left Ventricular Hypertrophy Rates Among Young Adults with Ischemic Stroke.

OBJECTIVES: Few studies have addressed Black-White differences in left ventricular hypertrophy (LVH) in young stroke patients without a history of hypertension. METHODS: A case-only cross-sectional analysis performed in 2019 of data from the Stroke Prevention in Young Adults Study, a population-based case-control study of ischemic stroke patients ages 15-49. The main outcomes were hypertension indicators at the time of stroke hospitalization: self-reported history of hypertension, LVH by echocardiography (Echo-LVH) and LVH by electrocardiogram (ECG-LVH). The prevalence of Echo-LVH was further determined in those with and without a history of hypertension. Adjusted odds ratios and 95% confidence intervals comparing blacks and whites were calculated by logistic regression. RESULTS: The study population included 1028 early-onset ischemic stroke patients, 48% Black cases, 54% men, median age 43 years (interquartile range, 38-46 years). Overall, the prevalence of hypertension history, Echo-LVH and ECG-LVH were 41.3%, 34.1% and 17.5%, respectively. Each of the hypertension indicators were more frequent in men than in women and in Black cases than in White cases. Black patients without a history of hypertension had higher rates of Echo-LVH than their white counterparts, 40.3% vs 27.7% (age and obesity adjusted OR 1.8; 95% CI 1.02-3.4) among men and 20.9% vs 7.6% (adjusted OR 2.7; 95% CI 1.2-6.2) among women. CONCLUSIONS: LVH was common in young patients with ischemic stroke, regardless of self-reported history of hypertension. These findings emphasize the need for earlier screening and more effective treatment of hypertension in young adults, particularly in the Black population.

Serious cycling-related fractures in on and off-road accidents: A retrospective analysis in the Australian Capital Territory region.

Cycling is an increasingly popular activity which is widely supported by health advocates. In the last year, more than a third of Australians used a bike [1]. While road cycling remains popular, participation in off-road recreational cycling, including mountain biking, bicycle moto cross (BMX) riding, and outdoor leisure cycling, is increasing and this is associated with an increase in the number and cost of cycling injuries [2-5]. The aim of this study was to describe and compare contemporary patterns of cycling fracture requiring hospitalisation as a function of cycling mode in the Australian Capital Territory region. This retrospective analysis of cycling-related-fracture hospitalisations in the ACT region described data recorded between July 2012 and December 2019. Logistic regression models were used to calculate probabilities of sustaining a fracture at different sites for each of the cycling modes (on-road, mountain, BMX, leisure, unspecified). These likelihoods were then compared against the on-road fracture profile. Cycling-related-fracture hospitalisations increased by 32% in the seven years analysed. Of all fracture admissions, 442 (33%) were on-road, 658 (49%) off-road, and 242 (18%) unknown. The majority were male (79%), median age 37 (IQR 16, 52). Median length of stay was two days. The number of fractures per admission ranged from one to thirteen with a median of one. Wrist, clavicle, ribs, and skull were the four most frequent fracture sites for all cycling modes. Fracture profiles of on- and off-road accidents were similar, with the exception of wrist fractures which were more likely in off-road (OR 1.96, p < 0.01) and unspecified cycling accidents (OR 5.07, p < 0.01). Skull fractures comprised 19% of all BMX-related fractures. More than half of all fracture-related admissions required surgery. With increasing support for sustainable and healthy transport and recreation activities, the fracture profiles of different cycling modes must first be assessed in order to inform strategies to reduce and manage this injury burden.

Differences in Multiple Risk Factors Between Black and White Individuals With Young-Onset Ischemic Stroke.

BACKGROUND AND OBJECTIVES: Stroke in young adults constitutes 15%-18% of all ischemic stroke cases. Black individuals have an excess risk of ischemic stroke especially in young adults. Although it is known that Black patients have a higher prevalence of hypertension and diabetes, few studies have addressed the association of concurrent multiple vascular risk factors with the excess risk of early-onset stroke among Black individuals. METHODS: A population-based case-control study of early-onset ischemic stroke, ages 15-49 years, was conducted in the Baltimore-Washington DC region between 1992 and 2007. Presence of the risk factors of obesity, hypertension, diabetes, and current smoking were obtained from both cases and controls by an in-person interview. Risk factor groups were defined as (1) 1 risk factor, (2) 2 risk factors, (3) 3 risk factors, and (4) 4 risk factors. Logistic regression analysis adjusting for age and sex was used to evaluate the association between each risk factor group and ischemic stroke compared with the reference group with no risk factors. RESULTS: The study included 1,034 cases and 1,091 controls. Of the cases, 47% were Black, 54% were men, and the mean (±SD) age was 41.0 (±6.9) years. The odds of having a stroke increased exponentially as the number of risk factors increased, 2.1, 2.6, 7.6, 16.5, all p < 0.001, for groups 1-4, respectively. When stratified by race, Black individuals were approximately 6 times more likely to have all 4 risk factors. DISCUSSION: The risk of stroke in young adults increased exponentially with the number of risk factors. Young Black patients with ischemic stroke were approximately 6 times more likely to have the co-occurrence of obesity, hypertension, diabetes, and smoking compared with their White counterparts. Targeting public health interventions to identify and improve care to Black young adults with multiple stroke risk factors may have substantial impact on lowering risk of stroke.

Black-White Differences in Ischemic Stroke Risk Factor Burden in Young Adults.

BACKGROUND AND PURPOSE: Although the US Black population has a higher incidence of stroke compared with the US White population, few studies have addressed Black-White differences in the contribution of vascular risk factors to the population burden of ischemic stroke in young adults. METHODS: A population-based case-control study of early-onset ischemic stroke, ages 15 to 49 years, was conducted in the Baltimore-Washington DC region between 1992 and 2007. Risk factor data was obtained by in-person interview in both cases and controls. The prevalence, odds ratio, and population-attributable risk percent (PAR%) of smoking, diabetes, and hypertension was determined among Black patients and White patients, stratified by sex. RESULTS: The study included 1044 cases and 1099 controls. Of the cases, 47% were Black patients, 54% were men, and the mean (±SD) age was 41.0 (±6.8) years. For smoking, the population-attributable risk percent were White men 19.7%, White women 32.5%, Black men 10.1%, and Black women 23.8%. For diabetes, the population-attributable risk percent were White men 10.5%, White women 7.4%, Black men 17.2%, and Black women 13.4%. For hypertension, the population-attributable risk percent were White men 17.2%, White women 19.3%, Black men 45.8%, and Black women 26.4%. CONCLUSIONS: Modifiable vascular risk factors account for a large proportion of ischemic stroke in young adults. Cigarette smoking was the strongest contributor to stroke among White patients while hypertension was the strongest contributor to stroke among Black patients. These results support early primary prevention efforts focused on smoking cessation and hypertension detection and treatment.

Simulation-Based Assessment of Graduate Neurology Trainees' Performance Managing Acute Ischemic Stroke.

BACKGROUND AND OBJECTIVES: Multidisciplinary acute stroke teams improve acute ischemic stroke management but may hinder trainees' education, which in turn may contribute to poorer outcomes in community hospitals on graduation. Our goal was to assess graduate neurology trainee performance independently of a multidisciplinary stroke team in the management of acute ischemic stroke, tissue plasminogen activator (tPA)-related hemorrhage, and cerebral herniation syndrome. METHODS: In this prospective, observational, single-center simulation-based study, participants (subinterns to attending physicians) managed a patient with acute ischemic stroke followed by tPA-related hemorrhagic conversion leading to cerebral herniation. Critical actions were developed by a modified Delphi approach based on relevant American Heart Association guidelines and the Neurocritical Care Society's Emergency Neurologic Life Support protocols. The primary outcome measure was graduate neurology trainees' critical action item sum score. We sought validity evidence to support our findings by comparing performance across 4 levels of training. RESULTS: Fifty-three trainees (including 31 graduate neurology trainees) and 5 attending physicians completed the simulation. The mean sum of critical actions completed by graduate neurology trainees was 15 of 22 (68%). Ninety percent of graduate neurology trainees properly administered tPA; 84% immediately stopped tPA infusion after patient deterioration; but only 55% reversed tPA according to guidelines. There was a moderately strong effect of level of training on critical action sum score (level 1 mean [SD] score 7.2 [2.8] vs level 2 mean [SD] score 12.3 [2.6] vs level 3 mean [SD] score 13.3 [2.2] vs level 4 mean [SD] score 16.3 [2.4], p < 0.001, R 2 = 0.54). DISCUSSION: Graduate neurology trainees reassuringly perform well in initial management of acute ischemic stroke but frequently make errors in the treatment of hemorrhagic transformation after thrombolysis, suggesting the need for more education surrounding this low-frequency, high-acuity event. High-fidelity simulation holds promise as an assessment tool for acute stroke management performance.

The Maryland Acute Stroke Emergency Medical Services Routing Pilot: Expediting Access to Thrombectomy for Stroke.

Background: Mechanical thrombectomy (MT) is the standard of care for acute ischemic stroke caused by large vessel occlusion, but is not available at all stroke centers. Transfers between hospitals lead to treatment delays. Transport directly to a facility capable of MT based on a prehospital stroke severity scale score has been recommended, if transportation time is less than 30 min. Aims: We hypothesized that an Emergency Medical Services (EMS) routing algorithm for stroke, using the Los Angeles Motor Scale (LAMS) in the field, would improve time from last known well to MT, without causing patients to miss the IV Thrombolysis (IVT) window. Methods: An EMS algorithm in the Baltimore metro area using the LAMS was implemented. Patients suspected of having an acute stroke were assessed by EMS using the LAMS. Patients scoring 4 or higher and within 20 h from last known well, were transported directly to a Thrombectomy Center, if transport could be completed within 30 min. The algorithm was evaluated retrospectively with prospectively collected data at the Thrombectomy Centers. The primary outcome variables were proportion of patients with suspected stroke rerouted by EMS, proportion of rerouted ischemic stroke patients receiving MT, time to treatment, and whether the IVT window was missed. Results: A total of 303 patients were rerouted out of 2459 suspected stroke patients over a period of 6 months. Of diverted patients, 47% had acute ischemic stroke. Of these, 48% received an acute stroke treatment: 16.8% IVT, 17.5% MT, and 14% MT+IVT. Thrombectomy occurred 119 min earlier in diverted patients compared to patients transferred from other hospitals (P = 0.006). 55.3% of diverted patients undergoing MT and 38.2% of patients transferred from hospital to hospital were independent at 90 days (modified Rankin score 0-2) (P = 0.148). No patient missed the time window for IVT due to the extra travel time. Conclusions: In this retrospective analysis of prospectively acquired data, implementation of a pre-hospital clinical screening score to detect patients with suspected acute ischemic stroke due to large vessel occlusion was feasible. Rerouting patients directly to a Thrombectomy Center, based on the EMS algorithm, led to a shorter time to thrombectomy.

Optimizing the Recognition and Treatment of In-Hospital Stroke: Evaluation of the 2CAN Score.

OBJECTIVES: Stroke-like symptoms may be difficult to appreciate due to the high incidence of stroke mimics (e.g., delirium) in the inpatient population. Many centers have adopted inpatient-specific stroke protocols with the aim of improving time to diagnosis and treatment. We aimed to assess one of these instruments, the "2CAN" score, in our patient population. MATERIALS AND METHODS: A retrospective chart review was conducted for all inpatients for whom our Brain Attack Team (BAT) was called between January 2015 and June 2019. Patients were excluded if they had stroke prior to current admission, were in the emergency department at the time of BAT call, or had incomplete documentation. The 2CAN score was calculated for each patient. RESULTS: The BAT was activated 201 times, and 110 patients met inclusion criteria. Twenty percent of patients had a history of atrial fibrillation, 72% hypertension, and 36% diabetes. Median NIHSS was 14.5 (IQR 5-24). Only 18% of stroke calls occurred within 24 h of hospital admission. The mean 2CAN score was 2.8. Ninety-seven (88%) patients received a final diagnosis of ischemic stroke and 13 (12%) of stroke mimics. There was no difference between 2CAN scores in the stroke and mimic groups (P = 0.91). A 2CAN score of ≥ 2 had sensitivity 83.5%, specificity 23.1%, PPV 89.0%, and NPV 15.8% for stroke. CONCLUSIONS: The 2CAN score was derived and validated in a single academic center as a tool to recognize inpatient stroke. The 2CAN score had good sensitivity and positive predictive value for stroke in our cohort, but poor specificity.

Marijuana Use and the Risk of Early Ischemic Stroke: The Stroke Prevention in Young Adults Study.

BACKGROUND AND PURPOSE: Few studies have examined the dose-response and temporal relationships between marijuana use and ischemic stroke while controlling for important confounders, including the amount of tobacco smoking. The purpose of our study was to address these knowledge gaps. METHODS: A population-based case-control study with 1090 cases and 1152 controls was used to investigate the relationship of marijuana use and early-onset ischemic stroke. Cases were first-ever ischemic stroke between the ages of 15 and 49 identified from 59 hospitals in the Baltimore-Washington region. Controls obtained by random digit dialing from the same geographic region were frequency-matched to cases by age, sex, region of residence and, except for the initial study phase, race. After excluding subjects with cocaine and other vasoactive substance use, the final study sample consisted of 751 cases and 813 controls. All participants underwent standardized interviews to characterize stroke risk factors and marijuana use. Unconditional logistic regression analysis was used to assess the relationships between marijuana use and risk of ischemic stroke, adjusting for age, sex, race, study phase, the amount of current tobacco smoking, current alcohol use, hypertension, and diabetes. RESULTS: After adjusting for other risk factors, including the amount of current tobacco smoking, marijuana use was not associated with ischemic stroke, regardless of the timing of use in relationship to the stroke, including ever use, use within 30 days, and use within 24 hours. There was a nonsignificant trend towards increased stroke risk among those who smoked marijuana at least once a week (odds ratio, 1.9 [95% CI, 0.8-4.9]). CONCLUSIONS: These analyses do not demonstrate an association between marijuana use and an increased risk of early-onset ischemic stroke, although statistical power was limited for assessing the association among very heavy users.

Hospital Factors, Performance on Process Measures After Transient Ischemic Attack, and 90-Day Ischemic Stroke Incidence.

Background and Purpose: We determined the association between hospital factors, performance on transient ischemic attack (TIA) process measures, and 90-day ischemic stroke incidence. Methods: Longitudinal analysis of retrospectively obtained data on 9168 veterans ≥18 years with TIA presenting to the emergency department or inpatient unit at 69 Veterans Affairs hospitals with ≥10 eligible patients per year in fiscal years 2015 to 2018. Process measures were high/moderate potency statin within 7 days of discharge, antithrombotic by day 2, and hypertension control (<140/90 mm Hg) at 90 days. The outcome was 90-day stroke incidence. Results: During the 4-year study period, hospitals significantly increased statin use (adjusted odds ratio [aOR] per 1-year increase, 1.24 [95% CI, 1.17­1.32]; P<0.001), whereas neither hypertension control (P=0.44) nor antithrombotic use (P=0.82) improved over time. Hospitals that admitted a higher proportion of TIA patients versus emergency department discharge had significantly greater use of statins (aOR per 10-percentage point increase in the proportion of TIA patients admitted, 1.09 [1.03­1.16]; P=0.003) and antithrombotics (aOR per 10-percentage point increase in TIA patients admitted, 1.14 [1.06­1.23]; P<0.001). Hospitals with higher emergency physician staffing and lower TIA patient volume had greater use of antithrombotics (aOR per 1 full-time physician increase, 1.05 [1.01­1.08]; P=0.008 and aOR per 10-patient decrease in volume, 1.09 [1.01­1.16]; P=0.02). Higher emergency physician staffing was associated with lower 90-day stroke incidence (aOR per 1 full-time physician increase, 0.96 [0.92­0.99]; P=0.02) but other hospital factors were not. Conclusions: Hospitals admitting higher percentages of TIA patients and having higher emergency physician staffing have greater performance on select guideline-concordant process measures for TIA. Higher emergency physician staffing was associated with improved outcomes 90 days after TIA.

Current State of Targeted Radiometal-Based Constructs for the Detection and Treatment of Disease in the Brain.

The continual development of radiopharmaceutical agents for the field of nuclear medicine is integral to promoting the necessity of personalized medicine. One way to greatly expand the selection of radiopharmaceuticals available is to broaden the range of radionuclides employed in such agents. Widening the scope of development to include radiometals with their variety of physical decay characteristics and chemical properties opens up a myriad of possibilities for new actively targeted molecules and bioconjugates. This is especially true to further advance the imaging and treatment of disease in the brain. Over the past few decades, imaging of disease in the brain has heavily relied on agents which exploit metabolic uptake. However, through utilizing the broad range of physical characteristics that radiometals offer, the ability to target other processes has become more available. The varied chemistries of radiometals also allows for them to incorporated into specifically designed diverse constructs. A major limitation to efficient treatment of disease in the brain is the ability for relevant agents to penetrate the blood-brain barrier. Thus, along with efficient disease targeting, there must be intentional thought put into overcoming this challenge. Here, we review the current field of radiometal-based agents aimed at either imaging or therapy of brain disease that have been evaluated through at least in vivo studies.

CRISPR/Cas9 generated knockout mice lacking phenylalanine hydroxylase protein as a novel preclinical model for human phenylketonuria.

Phenylketonuria (PKU) is an autosomal recessive inborn error of L-phenylalanine (Phe) metabolism. It is caused by a partial or complete deficiency of the enzyme phenylalanine hydroxylase (PAH), which is necessary for conversion of Phe to tyrosine (Tyr). This metabolic error results in buildup of Phe and reduction of Tyr concentration in blood and in the brain, leading to neurological disease and intellectual deficits. Patients exhibit retarded body growth, hypopigmentation, hypocholesterolemia and low levels of neurotransmitters. Here we report first attempt at creating a homozygous Pah knock-out (KO) (Hom) mouse model, which was developed in the C57BL/6 J strain using CRISPR/Cas9 where codon 7 (GAG) in Pah gene was changed to a stop codon TAG. We investigated 2 to 6-month-old, male, Hom mice using comprehensive behavioral and biochemical assays, MRI and histopathology. Age and sex-matched heterozygous Pah-KO (Het) mice were used as control mice, as they exhibit enough PAH enzyme activity to provide Phe and Tyr levels comparable to the wild-type mice. Overall, our findings demonstrate that 6-month-old, male Hom mice completely lack PAH enzyme, exhibit significantly higher blood and brain Phe levels, lower levels of brain Tyr and neurotransmitters along with lower myelin content and have significant behavioral deficit. These mice exhibit phenotypes that closely resemble PKU patients such as retarded body growth, cutaneous hypopigmentation, and hypocholesterolemia when compared to the age- and sex-matched Het mice. Altogether, biochemical, behavioral, and pathologic features of this novel mouse model suggest that it can be used as a reliable translational tool for PKU preclinical research and drug development.

Exploring the Collateral Damage of the COVID-19 Pandemic on Stroke Care: A Statewide Analysis.

[Figure: see text].

Development of Neurological Emergency Simulations for Assessment: Content Evidence and Response Process.

OBJECTIVE: To document two sources of validity evidence for simulation-based assessment in neurological emergencies. BACKGROUND: A critical aspect of education is development of evaluation techniques that assess learner's performance in settings that reflect actual clinical practice. Simulation-based evaluation affords the opportunity to standardize evaluations but requires validation. METHODS: We identified topics from the Neurocritical Care Society's Emergency Neurological Life Support (ENLS) training, cross-referenced with the American Academy of Neurology's core clerkship curriculum. We used a modified Delphi method to develop simulations for assessment in neurocritical care. We constructed checklists of action items and communication skills, merging ENLS checklists with relevant clinical guidelines. We also utilized global rating scales, rated one (novice) through five (expert) for each case. Participants included neurology sub-interns, neurology residents, neurosurgery interns, non-neurology critical care fellows, neurocritical care fellows, and neurology attending physicians. RESULTS: Ten evaluative simulation cases were developed. To date, 64 participants have taken part in 274 evaluative simulation scenarios. The participants were very satisfied with the cases (Likert scale 1-7, not at all satisfied-very satisfied, median 7, interquartile range (IQR) 7-7), found them to be very realistic (Likert scale 1-7, not at all realistic-very realistic, median 6, IQR 6-7), and appropriately difficult (Likert scale 1-7, much too easy-much too difficult, median 4, IQR 4-5). Interrater reliability was acceptable for both checklist action items (kappa = 0.64) and global rating scales (Pearson correlation r = .70). CONCLUSIONS: We demonstrated two sources of validity in ten simulation cases for assessment in neurological emergencies.

A 5-Decade Analysis of Incidence Trends of Ischemic Stroke After Transient Ischemic Attack: A Systematic Review and Meta-analysis.

Importance: Management of transient ischemic attack (TIA) has gained significant attention during the past 25 years after several landmark studies indicated the high incidence of a subsequent stroke. Objective: To calculate the pooled event rate of subsequent ischemic stroke within 2, 7, 30, and 90 days of a TIA and compare this incidence among the population with TIA recruited before 1999 (group A), from 1999 to 2007 (group B), and after 2007 (group C). Data Sources: All published studies of TIA outcomes were obtained by searching PubMed from 1996, to the last update on January 31, 2020, irrespective of the study design, document type, or language. Study Selection: Of 11 516 identified citations, 175 articles were relevant to this review. Both the classic time-based definition of TIA and the new tissue-based definition were accepted. Studies with a combined record of patients with TIA and ischemic stroke, without clinical evaluation for the index TIA, with diagnosis of index TIA event after ischemic stroke occurrence, with low suspicion for TIA, or duplicate reports of the same database were excluded. Data Extraction and Synthesis: The study was conducted and reported according to the PRISMA, MOOSE, and EQUATOR guidelines. Critical appraisal and methodological quality assessment used the Quality in Prognosis Studies tool. Publication bias was visualized by funnel plots and measured by the Begg-Mazumdar rank correlation Kendall τ2 statistic and Egger bias test. Data were pooled using double arcsine transformations, DerSimonian-Laird estimator, and random-effects models. Main Outcomes and Measures: The proportion of the early ischemic stroke after TIA within 4 evaluation intervals (2, 7, 30, and 90 days) was considered as effect size. Results: Systematic review yielded 68 unique studies with 223 866 unique patients from 1971 to 2019. The meta-analysis included 206 455 patients (58% women) during a span of 4 decades. The overall subsequent ischemic stroke incidence rates were estimated as 2.4% (95% CI, 1.8%-3.2%) within 2 days, 3.8% (95% CI, 2.5%-5.4%) within 7 days, 4.1% (95% CI, 2.4%-6.3%) within 30 days, and 4.7% (95% CI, 3.3%-6.4%) within 90 days. There was a recurrence risk of 3.4% among group A in comparison with 2.1% in group B or 2.1% in group C within 2 days; 5.5% in group A vs 2.9% in group B or 3.2% in group C within 7 days; 6.3% in group A vs 2.9% in group B or 3.4% in group C within 30 days, and 7.4% in group A vs 3.9% in group B or 3.9% in group C within 90 days. Conclusions and Relevance: These findings suggest that TIA continues to be associated with a high risk of early stroke; however, the rate of post-TIA stroke might have decreased slightly during the past 2 decades.