Background: Cerebral venous thrombosis (CVT) is a rare cause of stroke, with 10–15% of patients experiencing dependence or death. The role of endovascular therapy (EVT) in the management of CVT remains controversial and practice patterns are not well-known. Methods: We distributed a comprehensive 53-question survey to neurologists, neuro-interventionalists, neurosurgeons and other relevant clinicians globally from May 2023 to October 2023. The survey asked about practice patterns and perspectives on EVT for CVT and assessed opinions regarding future clinical trials. Results: The overall response rate was 31% (863 respondents from 2744 invited participants) across 61 countries. A majority (74%) supported use of EVT for certain CVT cases. Key considerations for EVT included worsening level of consciousness (86%) and other clinical deficits (76%). Mechanical thrombectomy with aspiration (22%) and stent retriever (19%) were the most utilized techniques, with regional variations. Post-procedurally, low molecular weight heparin was the predominant anticoagulant administered (40%), although North American respondents favored unfractionated heparin. Most respondents supported future trials of EVT (90%). Conclusions: Our survey reveals significant heterogeneity in approaches to EVT for CVT, highlighting the necessity for adequately powered clinical trials to guide standard-of-care practices.

Background: Reducing oral corticosteroids (OCS) use can alleviate the risk of many adverse events related to long-term OCS use. Here, we evaluate real-world utilization of OCS among patients with generalized myasthenia gravis (gMG) over the first 6 months following efgartigimod initiation. Methods: Patients with gMG using OCS who initiated efgartigimod treatment were identified retrospectively from an open US medical and pharmacy claims database (IQVIA Longitudinal Access and Adjudication Data [LAAD], April 2016-April 2023). Average daily dose (ADD) of OCS was analyzed during the 3-month period preceding efgartigimod initiation, and at 3 and 6 months post-efgartigimod initiation. Results: Of 231 patients assessed, 17 (7.4%), 109 (47.1%), and 105 (45.5%) had baseline OCS ADD of 0–5 mg, 5–20 mg, or >20 mg, respectively. At 3 and 6 months post-efgartigimod, 82 (35%) and 99 (43%) patients, respectively, reduced ADD by ≥5 mg. Proportion of patients with ADD of 0–5 mg increased >3-fold (7% baseline vs. 26% 6 months post-efgartigimod) and proportion of patients with ADD of >20 mg decreased by 35% (45% baseline vs. 29% 6 months post-efgartigimod) following efgartigimod initiation. Conclusions: Approximately 43% of patients were able to decrease steroid use or achieved steroid-free status within 6 months of efgartigimod treatment initiation.

Investment managers connected to plans sponsors are more likely to be hired than not-connected managers. The magnitude of the selection effect is comparable to that of prior performance. Ex post, connections do not result in higher post-hiring returns. Relationships are thus conducive to asset gathering by investment managers but do not generate commensurate pecuniary benefits for plan sponsors.

Background: Women are reported to have worse outcomes than men following ischemic stroke despite similar treatment effects for thrombolysis and endovascular treatment. Methods: We performed a post-hoc analysis of patients with acute ischemic stroke and intracranial occlusion enrolled in INTERRSeCT, an international prospective cohort study. We compared workflow times, reperfusion therapy choices, and 90-day modified Rankin scale (mRS) scores. Results: We included 575 patients, mean age 70.2 years (SD: 13.1) and 48.5% female. There were no significant sex differences in onset-to-CT (males: 115 minutes [IQR: 72-171], females: 114 minutes [IQR: 75-196] ) or CT-to-thrombolysis time (males: 24 minutes [IQR: 17-32], females: 23 minutes [IQR: 18-36]). However, female participants had a 12-minute faster CT-to-groin-puncture time, p=0.001. Reperfusion therapies did not significantly differ by sex. Reperfusion therapies included thrombolysis alone (males: 46%, females: 49%), EVT alone (males: 34%, females: 34%), thrombolysis plus EVT (males: 8%, females 9%) and conservative management (males: 12%, females: 8%). Median 90-day mRS was 2 (IQR: 1-4) in both males and females, p=0.1. Conclusions: In the INTERRSeCT cohort, rates of reperfusion therapy, workflow times and 90-day outcomes were similar between sexes, suggesting that women are not subject to any poorer performance in key quality indicators for reperfusion treatment for acute stroke.

Background: Trials of endovascular thrombectomy (EVT) for acute stroke have excluded patients with pre-morbid disability. We performed a meta-analysis to assess the effectiveness and safety of EVT in patients with pre-morbid disability. Methods: According to PRISMA guidelines, we searched for studies describing outcomes in patients with pre-morbid disability (modified Rankin Scale [mRS] 2-5), treated with EVT or medical management (MM). Random-effects meta-analysis was used to pool outcomes including return to baseline mRS at 90 days, symptomatic ICH (sICH), and 90-day mortality. Results: We analyzed 14 studies of patients with pre-morbid disability (mRS2-5: EVT=1,373, MM=253). Compared to medical therapy, EVT was associated with higher likelihood of return to baseline mRS (OR=2.37, 95%CI:1.39-4.04) and a trend towards lower mortality (OR=0.68, 95%CI:0.46-1.02), with similar odds of sICH (OR 1.01, 95%CI:0.49-2.08). In studies comparing patients with vs. without pre-morbid disability treated with EVT, similar results were found except that pre-morbid disability, when defined more strictly as mRS 3-5, was associated with mortality (OR 3.49, p<0.001). Conclusions: In patients with pre-morbid disability, EVT carries a higher chance of return to baseline mRS compared to patients treated with MM or without pre-morbid disability, although with higher mortality than patients without pre-morbid disability. These findings merit validation with randomized controlled trials.

Background: Some patients do poorly despite small infarcts after endovascular therapy(EVT) whilst others with large infarcts do well. We validated exploratory findings from the ESCAPE trial regarding factors associated with such discrepancies, in the ESCAPE-NA1 trial(NCT02930018). Methods: We identified “discrepant cases” with modified Rankin Scale(mRS)≥3 despite small follow-up infarct volume(FIV≤25th-percentile) on 24-hour CT/MRI or mRS≤2 despite large FIV(volume≥75th-percentile). We compared area-under-the-curve(AUC) of pre-specified logistic models containing (a)pre-treatment factors(age/cancer/vascular risk-factors) and (b)treatment-related/post-treatment factors(serious adverse events/SAEs) in identifying small-FIV/mRS≥3 and large-FIV/mRS≤2, with stepwise regression-derived models. Results: Among 1,091 patients, 42/287(14.6%) with FIV≤7mL(25th-percentile) had mRS≥3; 65/275(23.6%) with FIV≥92mL(75th-percentile) had mRS≤2. Pre-specified pre-treatment factors(age/cancer/vascular risk-factors) were associated with FIV≤7mL/mRS≥3; stepwise models selected similar variables(similar AUCs:0.92-0.93,p=0.42). SAEs(infarct-in-new-territory/recurrent stroke/pneumonia/heart failure) were strongly associated with FIV≤7mL/mRS≥3; stepwise models also identified onset-to-needle time and hemoglobin(24-hours) as treatment-related/post-treatment factors(similar AUCs:0.92-0.94,p=0.14). Younger age was associated with FIV≥92mL/mRS≤2; stepwise models also selected diabetes absence and baseline hemoglobin(similar AUCs:0.76-0.77,p=0.82). Absence of SAEs(stroke progression/pneumonia/intracerebral hemorrhage) was strongly associated with FIV≥92mL/mRS≤2; stepwise models also identified 24-hour hemoglobin, glucose, and BP(similar AUCs:0.79-0.80,p=0.030). Conclusions: FIV-mRS discrepancies are associated with pre-treatment factors like age/comorbidities; and post-treatment complications related to stroke evolution, secondary prevention, and post-acute care quality. Optimizing thrombolysis speed, BP, glucose, and hemoglobin are modifiable factors meriting further study.

Background: There are no recommendations regarding endovascular treatment (EVT) for patients with acute ischemic stroke (AIS) due to primary medium vessel occlusion (MeVO). The aim of this study was to examine the willingness to perform EVT among stroke physicians in patients with mild, yet personally-disabling deficits due to MeVO. Methods: In an international survey consisting of 4 cases of primary MeVOs, participants were asked whether the presence of personally-disabling deficits would influence their decision-making for EVT despite the patients having low NIHSS scores. Decision rates were calculated based on physician characteristics. Clustered univariable logistic regression was performed. Results: 366 participants from 44 countries provided 2562 answers. 56.9% opted to perform EVT in scenarios in which the deficit was relevant to the patient’s profession versus 41.0% in which no information regarding patient profession was provided (RR1.39, p<0.001). The largest effect sizes were seen for female participants (RR1.68, 95%CI:1.35-2.09), participants >60 years (RR1.61, 95%CI:1.23-2.10), with more neurointervention experience (RR1.60, 95%CI:1.24-2.06), and who personally performed >100 EVTs per year (RR1.63, 95%CI:1.22-2.17). Conclusions: The presence of a patient-relevant deficit in low NIHSS AIS due to MeVO is an important factor for EVT decision-making. This may have relevance for the conduct and interpretation of low NIHSS EVT randomized trials.

Background: Thrombus embolization during endovascular treatment (EVT) occurs in up to 9% of cases, making secondary medium-vessel occlusions (MeVOs) of particular interest to neurointerventionalists. We sought to gain insight into the current EVT approaches for secondary MeVO stroke in an international case-based survey as there are currently no clear recommendations for EVT in these patients. Methods: Participants were presented with three secondary MeVO cases, each consisting of three case-vignettes with changes in patient neurological status (improvement, no change, unable to assess). Clustered multivariable logistic regression analyses were used to assess factors influencing the decision to treat. Results: 366 physicians from 44 countries took part. The majority (54.1%) were in favor of EVT. Participants were more likely to treat occlusions in the anterior M2/3 (74.3%; risk ratio [RR]2.62, 95%CI:2.27-3.03) or A3 (59.7%; RR2.11, 95%CI:1.83-2.42) segment, compared to the M3/4 segment (28.3%;reference). Physicians were less likely to pursue EVT in patients with neurological improvement (49.9% versus 57.0%; RR0.88, 95%CI:0.83-0.92). Interventionalists and more experienced physicians were more likely to treat secondary MeVOs. Conclusions: Physician’s willingness to treat secondary MeVOs endovascularly is limited and varies per occlusion location and change in neurological status. More evidence on the safety and efficacy of EVT for secondary MeVO stroke is needed.

Background: Predicting outcomes after endovascular treatment (EVT) for acute ischemic stroke with baseline variables remains a challenge. We assessed the performance of stroke outcome prediction models for EVT in acute ischemic stroke in an iterative fashion using baseline, treatment-related and post-treatment variables. Methods: Data from the ESCAPE-NA1 trial were used to build 4 outcome prediction models using multi-variable logistic regression: Model 1 included baseline variables only that are available prior to treatment decision-making, model 2 included additional treatment-related variables, model 3 additional early post-treatment variables, and model 4 additional late post-treatment variables. The primary outcome was 90-day modified Rankin Scale score 0-2. Model performance was compared using the area under the curve (AUC). Results: Among 1,105 patients, good outcome was achieved by 666 (60.3%). When using baseline variables only (model 1), the AUC was 0.74 (95%CI:0.71-0.77); this iteratively improved when treatment and post-treatment variables were added to the models (model 2: AUC 0.77,95%CI: 0.74-0.80, model 3: AUC 0.80,95%CI:0.77-0.83, model 4: AUC 0.82, 95%CI:0.79-0.85). Conclusions: Predicting EVT outcomes using baseline variables alone is inaccurate in one in four patients, and may be inappropriate for patient selection. Even the most comprehensive models with treatment-related and post-treatment factors involve considerable uncertainty.

Background: Small brain infarcts are often seen on diffusion-weighted MRI(DWI) following surgical/endovascular procedures. Little is known about their clinical effects. We examined the association of iatrogenic infarcts with outcomes in the ENACT(Evaluating Neuroprotection in Aneurysm Coiling Therapy) trial of nerinetide in endovascular aneurysm repair. Methods: In this post-hoc analysis, we used multi-variable models to evaluate the association of presence/number of DWI iatrogenic infarcts with NIHSS(National Institutes of Health Stroke Scale), mRS(modified Rankin Scale), and cognitive/neuropsychological scores(30-minute battery) at 1-4 and 30-days post-procedure. We also related infarct number to a Z-score-derived composite outcome score(quantile regression). Results: Among 185 patients(median age:56,IQR:50-64), 124(67.0%) had iatrogenic infarcts(median:4,IQR:2-10.5). Nerinetide resulted in fewer infarcts. Patients with infarcts had lower Mini-Mental State Exam(MMSE) scores at 2-4 days(median:28 vs 29, adjusted-coefficient[acoef] per additional infarct:-1.11,95%CI:-1.88 to -0.34,p=0.005). Infarct number was associated with worse day-1 NIHSS(aOR for NIHSS≥1:1.07,1.02-1.12,p=0.009), day 2-4 mRS(adjusted common odds-ratio[aOR]:1.05,1.01-1.09,p=0.005) and MMSE(acoef:-0.07,-0.13 to -0.003,p=0.040), 30-day mRS(aOR:1.04,1.01-1.07,p=0.016) and Hopkins Verbal Learning Test scores(acoef:-0.21,-0.39 to -0.03,p=0.020), as well as worse composite scores at 1-4 and 30-days(acoef:-0.09,-0.15 to -0.03,p=0.006). Conclusions: Iatrogenic infarcts were associated with subtle differences in post-procedural(1-4 days) and 30-day outcomes in this middle-aged cohort. Future studies should use batteries of similar/greater granularity to validate optimal measures for short- versus long-term manifestations.

Background: Decisions to treat large-vessel occlusion with endovascular therapy(EVT) or intravenous alteplase depend on how physicians weigh benefits against risks when considering patients’ pre-stroke comorbidities. Methods: In an international survey, experts chose treatment approaches under current resources and under assumed ideal conditions for 10 of 22 randomly assigned case-scenarios. Five included comorbidities(metastatic/non-metastatic cancer, cardiac/respiratory/renal disease, non-disabling/mild cognitive impairment[MCI], physical dependence). We examined scenario/respondent characteristics associated with EVT/alteplase decisions using multivariable logistic regressions. Results: Among 607 physicians(38 countries), EVT was favoured in 1,097/1,379(79.6%) responses for comorbidity-related scenarios under current resources versus 1,510/1,657(91.1%,OR:0.38, 95%CI.0.31-0.47) for six “level-1A” scenarios (assuming ideal conditions:82.7% vs 95.1%,OR:0.25,0.19-0.33). However, this was reversed on including all other scenarios(e.g. under current resources:3,489/4,691[74.4%], OR:1.34,1.17-1.54). Responses favouring alteplase for comorbidity-related(e.g.75.0% under current resources) scenarios were comparable to level-1A scenarios(72.2%) and higher than all others(60.4%). No comorbidity-related factor independently diminished EVT-odds. MCI and dependence carried higher alteplase-odds; cancer and cardiac/respiratory/renal disease had lower odds. Relevant respondent characteristics included performing more EVT cases/year (higher EVT, lower alteplase-odds), practicing in East-Asia (higher EVT-odds), and in interventional neuroradiology(lower alteplase-odds vs neurology). Conclusions: Moderate-to-severe comorbidities did not consistently deter experts from EVT, suggesting equipoise about withholding EVT based on comorbidities. However, alteplase was often foregone when respondents chose EVT.

OBJECTIVES/GOALS: In 2016, more than 3,100 children died, and an estimated 17,000 children had non-fatal injuries, from firearms in the United States. In this study, we used hospital charges as a proxy for medical resource utilization, and compared differences in charges by intent of firearm injury among children. METHODS/STUDY POPULATION: In this cross-sectional study of the 2016 Nationwide Emergency Department Sample, we identified firearm injury cases among children aged 19 years or younger using ICD-10-CM external cause of morbidity codes. Injury intent was characterized as unintentional, assault, self-inflicted, undetermined, or due to legal intervention. We included patients treated and released from the emergency department (ED) or admitted alive to the hospital, and excluded those who were transferred or died in the ED. We used linear regressions with survey weighting to compare differences in mean healthcare charges by firearm injury intent, with and without adjustment for ED disposition. RESULTS/ANTICIPATED RESULTS: Among 12,469 cases in the weighted sample, mean age was 16.5 years, a majority were male (88.2%) and Medicaid-insured (57.8%), and 64% were discharged from the ED and 36% admitted. Injuries were 49.0% unintentional, 45.1% assault-related, and 1.8% self-inflicted. Compared to children with self-inflicted injuries (charges $115,224), children with assault-related injuries (charges $55,052; p<0.007) and unintentional injuries (charges $38,643; p<0.001) had lower mean charges per visit. Differences in charges were no longer significant after adjusting for ED disposition, as 85.8% of self-inflicted injuries were admitted, compared to 46.5% of assault-related and 24.3% of unintentional injuries. DISCUSSION/SIGNIFICANCE OF IMPACT: Although the majority of pediatric firearm-related injuries resulting in emergency department care are unintentional or assault-related, self-inflicted injuries result in greater per visit hospital charges, attributable to higher hospitalization rates, and likely due to more severe injuries.