The differential proteomic response to ischemic stroke in appalachian subjects treated with mechanical thrombectomy.

INTRODUCTION: The Appalachia region of North America is known to have significant health disparities, specifically, worse risk factors and outcomes for stroke. Appalachians are more likely to have comorbidities related to stroke, such as diabetes, obesity, and tobacco use, and are often less likely to have stroke interventions, such as mechanical thrombectomy (MT), for emergent large vessel occlusion (ELVO). As our Comprehensive Stroke Center directly serves stroke subjects from both Appalachian and non-Appalachian areas, inflammatory proteomic biomarkers were identified associated with stroke outcomes specific to subjects residing in Appalachia. METHODS: There were 81 subjects that met inclusion criteria for this study. These subjects underwent MT for ELVO, and carotid arterial blood samples acquired at time of intervention were sent for proteomic analysis. Samples were processed in accordance with the Blood And Clot Thrombectomy Registry And Collaboration (BACTRAC; clinicaltrials.gov; NCT03153683). Statistical analyses were utilized to examine whether relationships between protein expression and outcomes differed by Appalachian status for functional (NIH Stroke Scale; NIHSS and Modified Rankin Score; mRS), and cognitive outcomes (Montreal Cognitive Assessment; MoCA). RESULTS: No significant differences were found in demographic data or co-morbidities when comparing Appalachian to non-Appalachian subjects. However, time from stroke onset to treatment (last known normal) was significantly longer and edema volume significantly higher in patients from Appalachia. Further, when comparing Appalachian to non-Appalachian subjects, there were significant unadjusted differences in the NIHSS functional outcome. A comprehensive analysis of 184 proteins from Olink proteomic (92 Cardiometabolic and 92 Inflammation panels) showed that the association between protein expression outcomes significantly differed by Appalachian status for seven proteins for the NIHSS, two proteins for the MoCA, and three for the mRS. CONCLUSION: Our study utilizes an ELVO tissue bank and registry to investigate the intracranial/intravascular proteomic environment occurring at the time of thrombectomy. We found that patients presenting from Appalachian areas have different levels of proteomic expression at the time of MT when compared to patients presenting from non-Appalachian areas. These proteins differentially relate to stroke outcome and could be used as prognostic biomarkers, or as targets for novel therapies. The identification of a disparate proteomic response in Appalachian patients provides initial insight to the biological basis for health disparity. Nevertheless, further investigations through community-based studies are imperative to elucidate the underlying causes of this differential response.

Ten-year trends, disparities, and clinical impact of stroke thrombectomy and thrombolysis: A single center experience 2012-2021.

OBJECTIVES: As indications for acute ischemic stroke treatment expand, it is unclear whether disparities in treatment utilization and outcome still exist. The main objective of this study was to investigate disparities in acute ischemic stroke treatment and determine impact on outcome. MATERIALS AND METHODS: Retrospective observational cohort study of consecutive ischemic stroke admissions to a comprehensive stroke center from 2012-2021 was performed. Primary exposure was intravenous thrombolysis and/or endovascular thrombectomy. Primary end points were discharge modified Rankin Scale, home disposition, and expired/hospice. Multivariable logistic regression analyses were conducted to elucidate disparities in treatment utilization and determine impact on outcome. RESULTS: Of 517,615 inpatient visits, there were 7,540 (1.46 %) ischemic stroke admissions, increasing from 1.14 % to 1.79 % from 2012-2021. Intravenous thrombolysis significantly decreased from 14.4 % to 9.8 % while endovascular thrombectomy significantly increased from 0.8 % to 10.5 %. Both intravenous thrombolysis and endovascular thrombectomy increased odds of discharge home and modified Rankin Scale 0-2, and thrombectomy decreased odds of expired/hospice. After adjusting for covariates, decreased odds of thrombectomy was associated with Medicaid insurance (Odds Ratio [95 % Confidence Interval] 0.55 [0.32-0.93]), age 80+ (0.49 [0.35-0.69]), prior stroke (0.49 [0.31-0.77]), and diabetes mellitus (0.55 [0.39-0.79]), while low median household income (<$80,000/year) increased odds of no acute treatment (1.34 [1.16-1.56]). No sex or racial disparities were observed. Medicaid and low-income were not associated with worse clinical outcomes. CONCLUSIONS: Less endovascular thrombectomy occurred in Medicaid, older, prior stroke, and diabetic patients, while low-income was associated with no treatment. The observed socioeconomic disparities did not impact discharge outcome.

Risk Factors and Prognosis of Early Neurological Deterioration after Bridging Therapy.

BACKGROUND: Early neurological deterioration (END) after bridging therapy (BT) of acute ischemic stroke (AIS) patients is associated with poor outcomes. OBJECTIVE: We aimed to study the incidence, risk factors and prognosis of END after BT. METHODS: From January to December 2021, the clinical data of AIS patients treated by BT (intravenous thrombolysis with alteplase prior to mechanical thrombectomy) from three comprehensive stroke centers were analyzed. Patients were divided into non-END group and END group according to whether they developed END within 72 hours of symptom onset. Modified Rankin scale (mRS) was used to assess the patient's prognosis at 90 days, and favorable outcomes were defined as mRS≤2. The incidence of END was investigated, and binary logistic regression analysis was used to explore its associated factors. RESULTS: The incidence of END after BT was 33.67%. The eligible 90 patients included 29 cases in the END group and 61 cases in the non-END group. Multivariate Logistic regression analysis showed that increase of systolic blood pressure (SBP) (OR=1.026, 95%CI:1.001-1.051, p =0.043), higher level of blood glucose at admission (OR=1.389, 95%CI:1.092-1.176, p =0.007) and large artery atherosclerosis (LAA) subtype (OR=8.009, 95%CI:2.357-27.223, p =0.001) were independent risk factors of END. Compared with the non-END group, the END group had significantly lower rates of good outcomes (6.90% versus 65.57%, p =0.001) while higher rates of mortality (44.83% versus 4.92%, p =0.001). CONCLUSION: It was found that the incidence of END after BT in AIS patients was 33.67%. An increase in SBP, higher glucose levels at admission, and LAA were independent risk factors of END that predicted a poor prognosis.

Predicting Futile Recanalization in Acute Ischemic Stroke Patients Undergoing Endovascular Thrombectomy: The Role of White Blood Cell Count to Mean Platelet Volume Ratio.

BACKGROUND: Approximately half of AIS patients have an unfavorable outcome even after complete reperfusion. White blood cell (WBC) count to mean platelet volume (MPV) ratio (WMR) may be a promising predictive factor for futile recanalization. This study aimed to determine the predictive value of WMR in identifying individuals at higher risk of futile recanalization. METHODS: In this retrospective cohort study, 296 patients who achieved complete reperfusion after endovascular treatment (EVT) were included in the analysis. WBC count and MPV were collected at admission. Multivariable logistic regression was used to examine the independent association of the WMR with functional outcomes at three months. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) analyses were used to compare the accuracy of WMR for predicting futile recanalization. RESULTS: The adjusted odds ratios for the fourth quartile of WMR were 3.142 (95% CI 1.405- 7.027, P = 0.005) for unfavorable outcomes at 3 months in comparison with the first quartile. The inclusion of WMR in the traditional model enabled a more accurate prediction of unfavorable outcomes (NRI 0.250, P = 0.031; IDI 0.022, P = 0.017). CONCLUSION: Elevated WMR at admission was independently associated with futile recanalization among AIS patients who received EVT and might be useful in identifying futile recanalization.

Oxygen Saturation and Postoperative Mortality in Patients With Acute Ischemic Stroke Treated by Endovascular Thrombectomy.

BACKGROUND: Monitored anesthesia care (MAC) and general anesthesia (GA) with endotracheal intubation are the 2 most used techniques for patients with acute ischemic stroke (AIS) undergoing endovascular thrombectomy. We aimed to test the hypothesis that increased arterial oxygen concentration during reperfusion period is a mechanism underlying the association between use of GA (versus MAC) and increased risk of in-hospital mortality. METHODS: In this retrospective cohort study, data were collected at the Cleveland Clinic between 2013 and 2018. To assess the potential mediation effect of time-weighted average oxygen saturation (Spo2) in first postoperative 48 hours between the association between GA versus MAC and in-hospital mortality, we assessed the association between anesthesia type and post-operative Spo2 tertiles (exposure-mediator relationship) through a cumulative logistic regression model and assessed the association between Spo2 and in-hospital mortality (mediator-outcome relationship) using logistic regression models. Confounding factors were adjusted for using propensity score methods. Both significant exposure-mediator and significant mediator-outcome relationships are needed to suggest potential mediation effect. RESULTS: Among 358 patients included in the study, 104 (29%) patients received GA and 254 (71%) received MAC, with respective hospital mortality rate of 19% and 5% (unadjusted P value <.001). GA patients were 1.6 (1.2, 2.1) (P < .001) times more likely to have a higher Spo2 tertile as compared to MAC patients. Patients with higher Spo2 tertile had 3.8 (2.1, 6.9) times higher odds of mortality than patients with middle Spo2 tertile, while patients in the lower Spo2 tertile did not have significant higher odds compared to the middle tertile odds ratio (OR) (1.8 [0.9, 3.4]; overall P < .001). The significant exposure-mediator and mediator-outcome relationships suggest that Spo2 may be a mediator of the relationship between anesthetic method and mortality. However, the estimated direct effect of GA versus MAC on mortality (ie, after adjusting for Spo2; OR [95% confidence interval {CI}] of 2.1 [0.9-4.9]) was close to the estimated association ignoring Spo2 (OR [95% CI] of 2.2 [1.0-5.1]), neither statistically significant, suggesting that Spo2 had at most a modest mediator role. CONCLUSIONS: GA was associated with a higher Spo2 compared to MAC among those treated by endovascular thrombectomy for AIS. Spo2 values that were higher than the middle tertile were associated with higher odds of mortality. However, GA was not significantly associated with higher odds of death. Spo2 at most constituted a modest mediator role in explaining the relationship between GA versus MAC and mortality.

Effect of Occlusion Site on the Safety and Efficacy of Intravenous Alteplase Before Endovascular Thrombectomy: A Prespecified Subgroup Analysis of DIRECT-MT.

BACKGROUND AND PURPOSE: Recent trials showed thrombectomy alone was comparable to bridging therapy in patients with anterior circulation large vessel occlusion eligible for both intravenous alteplase and endovascular thrombectomy. We performed this study to examine whether occlusion site modifies the effect of intravenous alteplase before thrombectomy. METHODS: This is a prespecified subgroup analysis of a randomized trial evaluating risk and benefit of intravenous alteplase before thrombectomy (DIRECT-MT [Direct Intra-Arterial Thrombectomy in Order to Revascularize AIS Patients With Large Vessel Occlusion Efficiently in Chinese Tertiary Hospitals]). Among 658 randomized patients, 640 with baseline occlusion site information were included. The primary outcome was the score on the modified Rankin Scale at 90 days. Multivariable ordinal logistic regression analysis with an interaction term was used to estimate treatment effect modification by occlusion location (internal carotid artery versus M1 versus M2). We report the adjusted common odds ratio for a shift toward better outcome on the modified Rankin Scale after thrombectomy alone compared with combination treatment adjusted for age, the National Institutes of Health Stroke Scale score at baseline, the time from stroke onset to randomization, the modified Rankin Scale score before stroke onset, and collateral score per the DIRECT-MT statistical analysis plan. RESULTS: The overall adjusted common odds ratio was 1.08 (95% CI, 0.82-1.43) with thrombectomy alone compared with combination treatment, and there was no significant treatment-by-occlusion site interaction (P=0.47). In subgroups based on occlusion location, we found the following adjusted common odds ratios: 0.99 (95% CI, 0.62-1.59) for internal carotid artery occlusions, 1.12 (95% CI, 0.77-1.64) for M1 occlusions, and 1.22 (95% CI, 0.53-2.79) for M2 occlusions. No treatment-by-occlusion site interactions were observed for dichotomized modified Rankin Scale distributions and successful reperfusion (extended thrombolysis in Cerebral Infarction score ≥2b) before thrombectomy. Differences in symptomatic hemorrhage rate were not significant between occlusion locations (internal carotid artery occlusion: 7.02% in bridging therapy versus 7.14% for thrombectomy alone, P=0.97; M1 occlusion: 5.06% versus 2.48%, P=0.22; M2 occlusion: 9.09% versus 4.76%; P=0.78). CONCLUSIONS: In this prespecified subgroup of a randomized trial, we found no evidence that occlusion location can inform intravenous alteplase decisions in endovascular treatment eligible patients directly presenting at endovascular treatment capable centers. Future studies are needed to confirm our findings. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03469206.

Endovascular Thrombectomy in Young Patients With Stroke: A MR CLEAN Registry Study.

BACKGROUND AND PURPOSE: Acute ischemic stroke due to large vessel occlusion is uncommon in young adults. We assessed stroke cause in young patients and compared their outcomes after endovascular thrombectomy with older patients. METHODS: We used data (March 2014 until November 2017) of patients with an anterior circulation large vessel occlusion stroke from the MR CLEAN (Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry, a nationwide, prospective study on endovascular thrombectomy in the Netherlands. We compared young patients (18-49 years) with older patients (≥50 years). Outcomes included modified Rankin Scale score after 90 days (both shift and dichotomized analyses), expanded Thrombolysis in Cerebral Infarction score, and symptomatic intracranial hemorrhage. Analyses were adjusted for confounding. RESULTS: We included 3256 patients, 310 (10%) were 18 to 49 years old. Young patients had lower median National Institutes of Health Stroke Scale scores (14 versus 16, P<0.001) and less cardiovascular comorbidities than older patients. Stroke etiologies in young patients included carotid dissection (16%), cardio-embolism (15%), large artery atherosclerosis (10%), and embolic stroke of undetermined source (31%). Clinical outcome was better in young than older patients (acOR for modified Rankin Scale shift: 1.8 [95% CI, 1.5-2.2]; functional independence [modified Rankin Scale score 0-2] 61 versus 39% [adjusted odds ratio, 2.1 [95% CI, 1.6-2.8]); mortality 7% versus 32%, adjusted odds ratio, 0.2 [95% CI, 0.1-0.3]). Symptomatic intracranial hemorrhage occurred less frequently in young patients (3% versus 6%, adjusted odds ratio, 0.5 [95% CI, 0.2-1.00]). Successful reperfusion (expanded Thrombolysis in Cerebral Infarction Score 2b-3) did not differ between groups. Onset to reperfusion time was shorter in young patients (253 versus 255 minutes, adjusted B in minutes 12.4 [95% CI, 2.4-22.5]). CONCLUSIONS: Ten percent of patients with acute ischemic stroke undergoing endovascular thrombectomy were younger than 50. Cardioembolism and carotid dissection were common underlying causes in young patients. In one-third of cases, no cause was identified, indicating the need for more research on stroke cause in young patients. Young patients had better prognosis and lower risk of symptomatic intracranial hemorrhage than older patients.

Institutional trends over a decade in catheter-directed interventions for pulmonary embolism.

OBJECTIVE: Catheter-directed interventions (CDIs) are commonly performed for acute pulmonary embolism (PE). The evolving catheter types and treatment algorithms impact the use and outcomes of these interventions. This study aimed to investigate the changes in CDI practice and their impact on outcomes. METHODS: Patients who underwent CDIs for PE between 2010 and 2019 at a single institution were identified from a prospectively maintained database. A PE team was launched in 2012, and in 2014 was established as an official Pulmonary Embolism Response Team. CDI annual use trends and clinical failures were recorded. Clinical success was defined as physiologic improvement in the absence of major bleeding, perioperative stroke or other procedure-related adverse event, decompensation for submassive or persistent shock for massive PE, the need for surgical thromboembolectomy, or death. Major bleeding was defined as requiring a blood transfusion, a surgical intervention, or suffering from an intracranial hemorrhage. RESULTS: There were 372 patients who underwent a CDI for acute PE during the study period with a mean age of 58.9 ± 15.4 years; there were males 187 (50.3%) and 340 patients has a submassive PE (91.4%). CDI showed a steep increase in the early Pulmonary Embolism Response Team years, peaking in 2016 with a subsequent decrease. Ultrasound-assisted thrombolysis was the predominant CDI technique peaking at 84% of all CDI in 2014. Suction thrombectomy use peaked at 15.2% of CDI in 2019. The mean alteplase dose with catheter thrombolysis techniques decreased from 26.8 ± 12.5 mg in 2013 to 13.9 ± 7.5 mg in 2019 (P < .001). The mean lysis time decreased from 17.2 ± 8.3 hours in 2013 to 11.3 ± 8.2 hours in 2019 (P < .001). Clinical success for the massive and the submassive PE cohorts was 58.1% and 91.2%, respectively; the major bleed rates were 25.0% and 5.3%. There were two major clinical success peaks, one in 2015 mirroring our technical learning curve and one in 2019 mirroring our patient selection learning curve. The clinical success decrease in 2018 was primarily derived from blood transfusions owing to acute blood loss during suction thrombectomy. CONCLUSIONS: CDIs for acute PE have rapidly evolved with high success rates. Multidisciplinary approaches among centers with appropriate expertise are advisable for the safe and successful implementation of catheter interventions.

Trends in interventional stroke device utilization during the COVID-19 pandemic.

OBJECTIVES: The collateral effect of the COVID-19 pandemic on interventional stroke care is not well described. We studied this effect by utilizing stroke device sales data as markers of interventional stroke case volume in the United States. METHODS: Using a real-time healthcare device sales registry, this observational study examined trends in the sales of thrombectomy devices and cerebral aneurysm coiling from the same 945 reporting hospitals in the U.S. between January 22 and June 31, 2020, and for the same months in 2018 and 2019 to allow for comparison. We simultaneously reviewed daily reports of new COVID-19 cases. The strength of association between the cumulative incidence of COVID-19 and procedural device sales was measured using Spearman rank correlation coefficient (CC). RESULTS: Device sales decreased for thrombectomy (- 3.7%) and cerebral aneurysm coiling (- 8.5%) when comparing 2019-2020. In 2020, thrombectomy device sales were negatively associated with the cumulative incidence of COVID-19 (CC - 0.56, p < 0.0001), with stronger negative correlation during April (CC - 0.97, p < 0.0001). The same negative correlation was observed with aneurysm treatment devices (CC - 0.60, p < 0.001), with stronger correlation in April (CC - 0.97, p < 0.0001). CONCLUSIONS: The decline in sales of stroke interventional equipment underscores a decline in associated case volumes. Future pandemic responses should consider strategies to mitigate such negative collateral effects.

Impact of Coronavirus Disease 2019 on Time Delay and Functional Outcome of Mechanical Thrombectomy in Tokyo, Japan.

OBJECTIVES: An association has been reported between delays in the onset-to-door (O2D) time for mechanical thrombectomy (MT) and outbreaks of coronavirus disease 2019 (COVID-19). However, the association between other MT time courses or functional outcomes and COVID-19 outbreaks remains unclear. We compared the time courses of stroke pathways or functional outcomes in 2020 (the COVID-19 era) with those in 2019 (the pre-COVID-19 era) in Tokyo, Japan. MATERIALS AND METHODS: This retrospective observational study used data from the Tokyo-tama-REgistry of Acute endovascular Thrombectomy (TREAT), a multicenter registry of MT for acute large vessel occlusion in the Tokyo Metropolitan Area. Patients who had undergone acute MT from January 2019 to December 2020 were included. Patients were classified by the year they had undergone MT (2019 or 2020). RESULTS: In total, 477 patients were analyzed. O2D time was significantly longer in 2020 (146.0 min) than in 2019 (105.0 min; p = 0.034). No significant difference in door-to-puncture time (D2P) time or modified Rankin Scale (mRS) score 0-2 at 90 days was seen between 2019 and 2020. In the subgroup analysis, O2D time was significantly longer in the first half of 2020 compared with 2019. Multivariable logistic regression analysis revealed that the year 2020 was a independent predictor of longer O2D time, but not for mRS score 0-2 at 90 days. CONCLUSIONS: Although O2D time was significantly longer in the COVID-19 compared with the pre-COVID-19 era, D2P may not be significantly delayed and functional outcomes may not be different, despite the COVID-19 pandemic.

Changes in Stroke Hospital Care During the COVID-19 Pandemic: A Systematic Review and Meta-Analysis.

[Figure: see text].

Impact of the SARS-COV-2 Pandemic on the Endovascular Treatment of Acute Stroke - an Italian Single-Center Experience.

OBJECTIVES: The SARS-CoV-2 pandemic greatly influenced the overall quality of healthcare. The purpose of this study was to compare the time variables for acute stroke treatment and evaluate differences in the pre-hospital and in-hospital care before and during the SARS-CoV-2 pandemic, as well as between the first and second waves. MATERIALS AND METHODS: Observational and retrospective study from an Italian hospital, including patients who underwent thrombectomy between January 1st 2019 and December 31st 2020. RESULTS: Out of a total of 594 patients, 301 were treated in 2019 and 293 in 2020. The majority observed in 2019 came from spoke centers (67,1%), while in 2020 more than half (52%, p < 0.01) were evaluated at the hospital's emergency room directly (ER-NCGH). When compared to 2019, time metrics were globally increased in 2020, particularly in the ER-NCGH groups during the period of the first wave (N = 24 and N = 56, respectively): "Onset-to-door":50,5 vs 88,5, p < 0,01; "Arrival in Neuroradiology - groin":13 vs 25, p < 0,01; "Door-to-groin":118 vs 143,5, p = 0,02; "Onset-to-groin":180 vs 244,5, p < 0,01; "Groin-to-recanalization": 41 vs 49,5, p = 0,03. When comparing ER-NCGH groups between the first (N = 56) and second (N = 49) waves, there was an overall improvement in times, namely in the "Door-to-CT" (47,5 vs 37, p < 0,01), "Arrival in Neuroradiology - groin" (25 vs 20, p = 0,03) and "Onset-to-groin" (244,5 vs 227,5, p = 0,02). CONCLUSIONS: During the SARS-CoV-2 pandemic, treatment for stroke patients was delayed, particularly during the first wave. Reallocation of resources and the shutting down of spoke centers may have played a determinant role.

Trends, Predictors and Outcomes of Ischemic Stroke Among Patients Hospitalized with Takotsubo Cardiomyopathy.

OBJECTIVES: This study assessed the temporal trends in the incidence of ischemic stroke among patients hospitalized with takotsubo cardiomyopathy (TCM) stratified by the subtypes of ischemic stroke (cardioembolic versus thrombotic). Predictors of each stroke subtype, the association with atrial fibrillation (AF), the occurrence of ventricular fibrillation/ventricular tachycardia (VF/VT), cardiogenic shock (CS), in-hospital mortality, length of stay (LOS), and total healthcare cost were also assessed. BACKGROUND: Ischemic stroke in TCM is thought to be primarily cardioembolic from left ventricular mural thromboembolism. Limited data are available on the incidence of thrombotic ischemic stroke in TCM. MATERIALS AND METHODS: We identified 27,970 patients hospitalized with the primary diagnosis of TCM from the 2008 to 2017 National Inpatient Sample, of which 751 (3%) developed ischemic stroke. Of those with ischemic stroke, 571 (76%) had thrombotic stroke while 180 (24%) had cardioembolic stroke. Cochrane armitage test was used to assess the incidence of thrombotic and cardioembolic strokes and multivariate regression was used to identify risk factors associated with each stroke subtype. We compared the incidence of AF, VF/VT, CS, LOS, in-hospital mortality and total cost between hospitalized patients with TCM alone to those with cardioembolic and thrombotic strokes. RESULTS: From 2008 - 2017, the incidence of thrombotic stroke (4.7%-9.5% (p< 0.0001) increased while it was unchanged for cardioembolic stroke (0.5%-0.7% P=0.5). In the multivariate regression, peripheral artery disease, prior history of stroke, and hyperlipidemia were significantly associated with thrombotic stroke, while CS, AF, and Asian race (compared to White race) were associated with cardioembolic stroke. Both cardioembolic and thrombotic strokes were associated with higher odds of IHM, AF, CS, longer LOS and increased cost. Trends in in-hospital mortality and the utilization of thrombolysis, cerebral angiography, and mechanical thrombectomy among patients with TCM and ischemic stroke were unchanged from 2008 to 2017. CONCLUSION: Among patients with TCM and ischemic stroke, thrombotic stroke was more common compared to cardioembolic stroke. Ischemic stroke was associated with poorer outcomes, including higher in-hospital mortality and increased healthcare resource utilization in TCM.

Perfusion Imaging and Clinical Outcome in Acute Ischemic Stroke with Large Core.

OBJECTIVE: Mechanical thrombectomy (MT) is not recommended for acute stroke with large vessel occlusion (LVO) and a large volume of irreversibly injured tissue ("core"). Perfusion imaging may identify a subset of patients with large core who benefit from MT. METHODS: We compared two cohorts of LVO-related patients with large core (>50 ml on diffusion-weighted-imaging or CT-perfusion using RAPID), available perfusion imaging, and treated within 6 hours from onset by either MT + Best Medical Management (BMM) in one prospective study, or BMM alone in the pre-MT era from a prospective registry. Primary outcome was 90-day modified Rankin Scale ≤2. We searched for an interaction between treatment group and amount of penumbra as estimated by the mismatch ratio (MMRatio = critical hypoperfusion/core volume). RESULTS: Overall, 107 patients were included (56 MT + BMM and 51 BMM): Mean age was 68 ± 15 years, median core volume 99 ml (IQR: 72-131) and MMRatio 1.4 (IQR: 1.0-1.9). Baseline clinical and radiological variables were similar between the two groups, except for a higher intravenous thrombolysis rate in the BMM group. The MMRatio strongly modified the clinical outcome following MT (pinteraction < 0.001 for continuous MMRatio); MT was associated with a higher rate of good outcome in patients with, but not in those without, MMRatio>1.2 (adjusted OR [95% CI] = 6.8 [1.7-27.0] vs 0.7 [0.1-6.2], respectively). Similar findings were present for MMRatio ≥1.8 in the subgroup with core ≥70 ml. Parenchymal hemorrhage on follow-up imaging was more frequent in the MT + BMM group regardless of the MMRatio. INTERPRETATION: Perfusion imaging may help select which patients with large core should be considered for MT. Randomized studies are warranted. ANN NEUROL 2021;90:417-427.

Ten-Year Trend in Age, Sex, and Racial Disparity in tPA (Alteplase) and Thrombectomy Use Following Stroke in the United States.

Background and Purpose: IV tPA (intravenous thrombolysis with alteplase) and mechanical thrombectomy (MT) utilization increased in acute ischemic stroke hospitalizations in the United States over the last decade. It is uncertain whether this increase occurred equally across all age, sex, and racial groups. Methods: Adult acute ischemic stroke hospitalizations (weighted n=4 442 657) contained in the 2008 to 2017 National Inpatient Sample were identified using International Classification of Diseases codes. Proportions of hospitalizations with IV tPA and MT were computed according to age, sex, and race. Joinpoint and multivariable-adjusted logistic regression models were used to evaluate trends over time. Results: Across this period, 32.4% of all hospitalizations were in patients ≥80 years, and 64.7% of these were women. IV tPA and MT use differed by age with highest proportion of utilization of both treatments in patients aged 18 to 39 years (IV tPA, 12.3%) and lowest percentage in patients aged ≥90 years (IV tPA, 7.9%). Utilization of both procedures increased over time in all age groups, but the pace of increase was faster in patients ≥90 years compared with patients aged 18 to 39 years (MT: odds ratio, 1.25 [95% CI, 1.20­1.35] per unit increase in year, P interaction <0.001). Frequency of utilization of IV tPA and MT was lower in Black patients compared with White patients in most age groups. Usage of both procedures increased over time in all races and after 2015, IV tPA utilization was >10% in all demographic subgroups except in Black patients 60 to 79 years and Black patients ≥80 years. Analysis of race-by-time interaction revealed the Black-vs-White treatment gaps for IV tPA (odds ratio, 1.02 [95% CI, 1.01­1.03]) and MT (odds ratio, 1.08 [95% CI,1.05­1.12]) declined over time (both P interaction <0.01). Sex-related differences in IV tPA use were noted, but this gap also declined over time. Conclusions: Age- and sex-related treatment gaps in IV tPA and MT reduced over the last decade. Racial disparity in IV tPA and MT utilization persists with particularly lower frequency of usage of both acute stroke treatments in Black patients compared with White patients, but race-associated treatment gaps also declined over time.

Penumbra Consumption Rates Based on Time-to-Maximum Delay and Reperfusion Status: A Post Hoc Analysis of the DEFUSE 3 Trial.

BACKGROUND AND PURPOSE: In patients with acute large vessel occlusion, the natural history of penumbral tissue based on perfusion time-to-maximum (Tmax) delay is not well established in relation to late-window endovascular thrombectomy. In this study, we sought to evaluate penumbra consumption rates for Tmax delays in patients with large vessel occlusion evaluated between 6 and 16 hours from last known normal. METHODS: This is a post hoc analysis of the DEFUSE 3 trial (The Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke), which included patients with an acute ischemic stroke due to anterior circulation occlusion within 6 to 16 hours of last known normal. The primary outcome is percentage penumbra consumption, defined as (24-hour magnetic resonance imaging infarct volume-baseline core infarct volume)/(Tmax 6 or 10 s volume-baseline core volume). We stratified the cohort into 4 categories based on treatment modality and Thrombolysis in Cerebral Infarction (TICI score; untreated, TICI 0-2a, TICI 2b, and TICI3) and calculated penumbral consumption rates in each category. RESULTS: We included 141 patients, among whom 68 were untreated. In the untreated versus TICI 3 patients, a median (interquartile range) of 53.7% (21.2%-87.7%) versus 5.3% (1.1%-14.6%) of penumbral tissue was consumed based on Tmax >6 s (P<0.001). In the same comparison for Tmax>10 s, we saw a difference of 165.4% (interquartile range, 56.1%-479.8%) versus 25.7% (interquartile range, 3.2%-72.1%; P<0.001). Significant differences were not demonstrated between untreated and TICI 0-2a patients for penumbral consumption based on Tmax >6 s (P=0.52) or Tmax >10 s (P=0.92). CONCLUSIONS: Among extended window endovascular thrombectomy patients, Tmax >10-s mismatch volume may comprise large volumes of salvageable tissue, whereas nearly half the Tmax >6-s mismatch volume may remain viable in untreated patients at 24 hours.

True first-pass effect in basilar artery occlusions: First-pass complete reperfusion improves clinical outcome in stroke thrombectomy patients.

BACKGROUND: Complete reperfusion (mTICI 3) in anterior circulation ischemic stroke patients after a single mechanical thrombectomy (MT) pass has been identified as a predictor of favorable outcome (modified Rankin Score 0-2) and defined as true first-pass effect recently. This effect has not yet been demonstrated in posterior circulation ischemic stroke. We hypothesized a true first-pass effect for the subgroup of acute basilar artery occlusions (BAO). METHODS: Consecutive patients with acute thromboembolic occlusions in the posterior circulation, treated between 2010 and 2017, were screened and all BAO patients with complete angiographic reperfusion and known symptom onset included for unmatched and matched analysis after adjustment for multiple confounding factors (demographics, time intervals, stroke severity, posterior circulation Alberta Stroke Program early computed tomography Score and comorbidity. The primary objective was outcome at 90 days between matched cohorts of single pass vs. multi pass complete reperfusion patients. RESULTS: 90 MTs in BAO were analyzed, yielding 56 patients with known symptom onset, in whom we achieved complete reperfusion (mTICI 3), depending on whether complete reperfusion was achieved after a single pass (n = 28) or multiple passes (n = 28). Multivariable analysis of 56 non-matched patients revealed a significant association between first-pass complete reperfusion and favorable outcome (p < 0.01). In matched cohorts (n = 7 vs. n = 7), favorable outcome was only seen if complete reperfusion was achieved after a single pass (86% vs. 0%). CONCLUSION: Single pass complete reperfusion in acute basilar artery occlusion is an independent predictor of favorable outcome. Achieving complete reperfusion after multiple passes might impair favorable patient recovery.

Novel peripheral blood cell ratios: Effective 3-month post-mechanical thrombectomy prognostic biomarkers for acute ischemic stroke patients.

BACKGROUND: Red blood cell distribution width to platelet ratio (RPR), Monocyte to high-density lipoprotein ratio (MHR), and Neutrophil to lymphocyte ratio (NLR) are novel inflammatory biomarkers in laboratory tests, which are associated with clinical outcomes in malignancy, cardiovascular and cerebrovascular diseases. This study aimed to determine their predictive value for the prognosis of acute ischemic stroke after mechanical thrombectomy (MT). METHODS: A total of 286 patients with acute ischemic stroke (AIS) admitted to a tertiary stroke center in China between January 2018 and February 2020 were treated by MT. Demographic characteristics, risk factors, clinical data, laboratory parameters, and clinical outcomes were recorded. The clinical outcome was disability or death at discharge or 90 days (defined as a modified Rankin Scale score of 3-6). The relationship between RPR, MHR, and NLR and functional outcomes was investigated by binary Logistic regression analysis, and further assessed by receiver operating characteristic curve (ROC). The Kaplan-Meier method was used to analyze the survival rate of prognosis factors. RESULTS: A total of 286 patients with AIS underwent MT (median age, 70.00; Interquartile range [IQR], 63.00-77.00; 41.6% female). Patients with unfavorable outcome showed higher RPR, MHR, and NLR than those with favorable outcome (RPR, [8.63; IQR, 6.30-10.78] vs [6.17; IQR, 5.11-7.35], P < 0.001; MHR, [0.40; IQR, 0.31-0.53] vs [0.34; IQR, 0.27-0.47], P = 0.005; NLR, [5.28; IQR, 3.63-8.02] vs [3.44; IQR, 2.63-4.63], P < 0.001). In multivariate and ROC curve analysis, higher RPR (>8.565) (odds ratio [OR], 1.671; 95% confidence interval [CI], 1.127-2.479; P = 0.011) and higher MHR (>0.368) (OR, 9.374; 95% CI, 1.160-75.767; P = 0.036), higher NLR (>4.030) (OR, 1.957; 95% CI, 1.382-2.770; P < 0.001) were independently associated with unfavorable outcome. The combined predictive value of the three indexes was higher than that of a single index. Kaplan-Meier survival curve analysis showed that the 90-day survival rate (82.1% vs 66.2%) was significantly different between the low RPR group and the high RPR group (χ2 = 4.960, P = 0.026). CONCLUSION: Higher RPR, MHR, and NLR might be independent risk factors for predicting 3-month poor prognosis in patients with AIS who underwent MT.

Predicting 90-Day Outcome After Thrombectomy: Baseline-Adjusted 24-Hour NIHSS Is More Powerful Than NIHSS Score Change.

BACKGROUND AND PURPOSE: The National Institutes of Health Stroke Scale (NIHSS) measured at an early time point is an appealing surrogate marker for long-term functional outcome of stroke patients treated with endovascular therapy. However, definitions and analytical methods for an early NIHSS-based outcome measure that optimize power and precision in clinical studies are not well-established. METHODS: In this post-hoc analysis of our prospective observational study that enrolled endovascular therapy-treated patients at 12 comprehensive stroke centers across the US, we compared the ability of 24-hour NIHSS, ΔNIHSS (baseline minus 24-hour NIHSS), and percentage change (NIHSS×100/baseline NIHSS), analyzed as continuous and dichotomous measures, to predict 90-day modified Rankin Scale (mRS) using logistic regression (adjusted for age, baseline NIHSS, glucose, hypertension, Alberta Stroke Program Early CT Score, time to recanalization, recanalization status, and intravenous thrombolysis) and Spearman ρ. RESULTS: Of 485 patients in the BEST (Blood Pressure After Endovascular Stroke Therapy) cohort, 446 (92%) with 90-day follow-up data were included. An absolute 24-hour NIHSS, adjusted for baseline in multivariable modeling, had the highest predictive power of all definitions evaluated (aR2 0.368 and adjusted odds ratio 0.79 [0.75-0.84], P<0.001 for mRS score 0-2; aR2 0.444 and adjusted odds ratio 0.84 [0.8-0.86] for ordinal mRS). For predicting mRS score of 0-2 with a cut point, the second most efficient approach, the optimal threshold for 24-hour NIHSS score was ≤7 (sensitivity 80.1%, specificity 80.4%; adjusted odds ratio 12.5 [7.14-20], P<0.001), followed by percent change in NIHSS (sensitivity 79%, specificity 58.5%; adjusted odds ratio 4.55 [2.85-7.69], P<0.001). CONCLUSIONS: Twenty-four-hour NIHSS, adjusted for baseline, was the strongest predictor of both dichotomous and ordinal 90-day mRS outcomes for endovascular therapy-treated patients. A dichotomous 24-hour NIHSS score of ≤7 was the second-best predictor. Although ΔNIHSS, continuous and dichotomized at ≥4, predicted 90-day outcomes, absolute 24-hour NIHSS definitions performed better.

International Survey of Mechanical Thrombectomy Stroke Systems of Care During COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic has strained the healthcare systems across the world but its impact on acute stroke care is just being elucidated. We hypothesized a major global impact of COVID-19 not only on stroke volumes but also on various aspects of thrombectomy systems. AIMS: We conducted a convenience electronic survey with a 21-item questionnaire aimed to identify the changes in stroke admission volumes and thrombectomy treatment practices seen during a specified time period of the COVID-19 pandemic. METHODS: The survey was designed using Qualtrics software and sent to stroke and neuro-interventional physicians around the world who are part of the Global Executive Committee (GEC) of Mission Thrombectomy 2020, a global coalition under the aegis of Society of Vascular and Interventional Neurology, between April 5th and May 15th, 2020. RESULTS: There were 113 responses to the survey across 25 countries with a response rate of 31% among the GEC members. Globally there was a median 33% decrease in stroke admissions and a 25% decrease in mechanical thrombectomy (MT) procedures during the COVID-19 pandemic period until May 15th, 2020 compared to pre-pandemic months. The intubation policy for MT procedures during the pandemic was highly variable across participating centers: 44% preferred intubating all patients, including 25% of centers that changed their policy to preferred-intubation (PI) from preferred non-intubation (PNI). On the other hand, 56% centers preferred not intubating patients undergoing MT, which included 27% centers that changed their policy from PI to PNI. There was no significant difference in rate of COVID-19 infection between PI versus PNI centers (p=0.60) or if intubation policy was changed in either direction (p=1.00). Low-volume (<10 stroke/month) compared with high-volume stroke centers (>20 strokes/month) were less likely to have neurointerventional suite specific written personal protective equipment protocols (74% vs 88%) and if present, these centers were more likely to report them to be inadequate (58% vs 92%). CONCLUSION: Our data provides a comprehensive snapshot of the impact on acute stroke care observed worldwide during the pandemic. Overall, respondents reported decreased stroke admissions as well as decreased cases of MT with no clear preponderance in intubation policy during MT. DATA ACCESS STATEMENT: The corresponding author will consider requests for sharing survey data. The study was exempt from institutional review board approval as it did not involve patient level data.