Endovascular thrombectomy time metrics in the era of COVID-19: observations from the Society of Vascular and Interventional Neurology Multicenter Collaboration

Background Unprecedented workflow shifts during the coronavirus disease 2019 (COVID-19) pandemic have contributed to delays in acute care delivery, but whether it adversely affected endovascular thrombectomy metrics in acute large vessel occlusion (LVO) is unknown. Methods We performed a retrospective review of observational data from 14 comprehensive stroke centers in nine US states with acute LVO. EVT metrics were compared between March to July 2019 against March to July 2020 (primary analysis), and between statespecific pre-peak and peak COVID-19 months (secondary analysis), with multivariable adjustment. Results Of the 1364 patients included in the primary analysis (51% female, median NIHSS 14 [IQR 7–21], and 74% of whom underwent EVT), there was no difference in the primary outcome of door-to-puncture (DTP) time between the 2019 control period and the COVID-19 period (median 71 vs 67min, P=0.10). After adjustment for variables associated with faster DTP, and clustering by site, there remained a trend toward shorter DTP during the pandemic (βadj=-73.2, 95%CI −153.8–7.4, Pp=0.07). There was no difference in DTP times according to local COVID-19 peaks vs pre-peak months in unadjusted or adjusted multivariable regression (βadj=-3.85, 95%CI −36.9–29.2, P=0.80). In this final multivariable model (secondary analysis), faster DTP times were significantly associated with transfer from an outside institution (βadj=-46.44, 95%CI −62.8 to – -30.0, P\u3c0.01) and higher NIHSS (βadj=-2.15, 95%CI −4.2to – -0.1, P=0.05). Conclusions In this multi-center study, there was no delay in EVT among patients treated for intracranial occlusion during the COVID-19 era compared with the pre-COVID era

Cerebrovascular events and outcomes in hospitalized patients with COVID-19: The SVIN COVID-19 Multinational Registry

© 2020 World Stroke Organization.[Background]: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has been associated with a significant risk of thrombotic events in critically ill patients. [Aim]: To summarize the findings of a multinational observational cohort of patients with SARS-CoV-2 and cerebrovascular disease. [Methods]: Retrospective observational cohort of consecutive adults evaluated in the emergency department and/or admitted with coronavirus disease 2019 (COVID-19) across 31 hospitals in four countries (1 February 2020–16 June 2020). The primary outcome was the incidence rate of cerebrovascular events, inclusive of acute ischemic stroke, intracranial hemorrhages (ICH), and cortical vein and/or sinus thrombosis (CVST). [Results]: Of the 14,483 patients with laboratory-confirmed SARS-CoV-2, 172 were diagnosed with an acute cerebrovascular event (1.13% of cohort; 1130/100,000 patients, 95%CI 970–1320/100,000), 68/171 (40.5%) were female and 96/172 (55.8%) were between the ages 60 and 79 years. Of these, 156 had acute ischemic stroke (1.08%; 1080/100,000 95%CI 920–1260/100,000), 28 ICH (0.19%; 190/100,000 95%CI 130–280/100,000), and 3 with CVST (0.02%; 20/100,000, 95%CI 4–60/100,000). The in-hospital mortality rate for SARS-CoV-2-associated stroke was 38.1% and for ICH 58.3%. After adjusting for clustering by site and age, baseline stroke severity, and all predictors of in-hospital mortality found in univariate regression (p < 0.1: male sex, tobacco use, arrival by emergency medical services, lower platelet and lymphocyte counts, and intracranial occlusion), cryptogenic stroke mechanism (aOR 5.01, 95%CI 1.63–15.44, p < 0.01), older age (aOR 1.78, 95%CI 1.07–2.94, p ¼ 0.03), and lower lymphocyte count on admission (aOR 0.58, 95%CI 0.34–0.98, p ¼ 0.04) were the only independent predictors of mortality among patients with stroke and COVID-19. [Conclusions]: COVID-19 is associated with a small but significant risk of clinically relevant cerebrovascular events, particularly ischemic stroke. The mortality rate is high for COVID-19-associated cerebrovascular complications; therefore, aggressive monitoring and early intervention should be pursued to mitigate poor outcomes

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Abstract Number ‐ 259: Recanalization Before Completion of Alteplase Infusion Leads to Improved Outcomes: A Retrospective Analysis

Introduction The recently published CHOICE trial found that intra‐arterial infusion of alteplase improved clinical outcomes in patients undergoing EVT for LVO AIS, an effect that was possibly due to a reduction in reperfusion‐related injury. Here, we examine whether intravenous alteplase, administered after successful endovascular reperfusion, results in improved clinical outcomes. Methods From our prospectively collected multicenter institutional registry drawn from four comprehensive stroke centers in the greater Houston area, we identified cases who underwent EVT with substantial reperfusion (TICI 2b/3) prior to termination of the intravenous alteplase continuous drip. Control patients were then identified as patients who underwent EVT with TICI 2b/3 after completion of intravenous alteplase, matching on age, baseline Modified Rankin Scale (mRS), initial NIH Stroke Scale (NIHSS), and comorbidities. The primary outcome was 90 day disability and was determined by mRS shift analysis, comparing the case and control populations. Results Among 21 cases and 24 matched controls, there were no significant difference between the mean age, gender, race, initial NIHSS, baseline mRS, or ASPECT score. Time from last known well to recanalization was longer in controls (48 min vs 151 min, p< 0.01). Patients who achieved reperfusion prior to termination of the alteplase continuous drip had better 90 day clinical outcomes relative to their presentation mRS when compared to patients who achieved reperfusion after termination of the alteplase. A change in mRS of 1 or less was seen in 71% vs 33% in the continued infusion group vs controls respectively. Conclusions Patients undergoing EVT who continued to be treated with intravenous alteplase following reperfusion had better 90d clinical outcomes relative to those with reperfusion after infusion termination. These findings further support the possible efficacy of thrombolytics following endovascular reperfusion

Abstract 1122‐000126: Mobile Stroke Unit Process Metrics in Large Vessel Occlusion Stroke Patients: BEST‐MSU Substudy

Introduction: Mobile Stroke Units (MSUs) speed thrombolytic treatment for acute ischemic stroke and improve clinical outcomes compared to standard management by Emergency Medical Services (EMS). However, MSU process metrics in the subset of patients with large vessel occlusions (LVOs) having endovascular thrombectomy (EVT) have yet to be optimized. Methods: A pre‐specified Benefits of Stroke Treatment Using a Mobile Stroke Unit (BEST‐MSU) substudy of tPA‐eligible stroke patients with imaging evident LVOs was conducted. The primary outcome was process metrics related to treatment times from stroke onset and first medical alert. Safety outcomes included rates of symptomatic intracerebral hemorrhage and procedural complications. Groups were compared using Chi‐square or Fisher’s exact tests for categorical variables, and Wilcoxon rank‐sum tests for continuous variables. Results: A total of 295 patients were included, 169 in the MSU group and 126 in the EMS group. Baseline characteristics were comparable between the groups, with the exception of baseline NIHSS (MSU mean 19.0 [IQR 13.0,23.0] vs EMS 16.0 [11.0, 20.0], p = 0.003). 92% of MSU and 87% of EMS LVO patients received tPA, and 78% and 85% went on to have EVT. Process metrics are detailed in Table 1. MSU LVO patients had faster tPA bolus from 911‐alert (MSU 45.0 minutes [40.0, 53.5] vs EMS 76.0 [64.0, 87.8], p<0.001), however the two groups had similar alert to groin puncture (MSU 142.5 [116.8, 171.0] versus EMS 131.5 [114.0, 159.8], p = 0.15). MSU patients spent more time on‐scene, (EMS arrival to ED arrival, 53.0 [45.0, 62.0] vs 27.0 [22.0, 33.0], p<0.001) however less time prior to EVT (door to groin puncture, 76.5 [54.8, 108.5] vs 94.0 [72.0, 123.0], p<0.001) with variable use of field CTAs and direct cath lab admission with ED bypass, yielding a net neutral result. The variability among site protocols is reflected in the range of median alert to groin puncture times (minimum 107.0 minutes, maximum 152.0). In the 222 patients undergoing EVT, median alert to recanalization time was 181.5 minutes [146.8, 225.5] in the MSU group and 190.5 [157.5, 227.5] in the EMS group (p = 0.47). Recanalization (Thrombolysis In Cerebral Infarction [TICI] 2b/3) was achieved in 76% of MSU and 70% of EMS (p = 0.32) with comparable rates of EVT complications (including hemorrhage, perforation, dissection, hematoma). 54% MSU and 44% of EMS LVO patients achieved good functional outcome (modified Rankin Scale [mRS] ≤ 2) at 90 days (p = 0.11). Conclusions: In tPA‐eligible LVO stroke patients, MSU management did not increase or expedite EVT treatment times as compared to standard EMS management. Future MSU processes should include field CTA with direct admission to cath labs to maximize the early treatment advantage this technology provides

Influence of the COVID-19 Pandemic on Treatment Times for Acute Ischemic Stroke

Background and Purpose: The pandemic caused by the novel coronavirus disease 2019 (COVID-19) has led to an unprecedented paradigm shift in medical care. We sought to evaluate whether the COVID-19 pandemic may have contributed to delays in acute stroke management at comprehensive stroke centers. Methods: Pooled clinical data of consecutive adult stroke patients from 14 US comprehensive stroke centers (January 1, 2019, to July 31, 2020) were queried. The rate of thrombolysis for nontransferred patients within the Target: Stroke goal of 60 minutes was compared between patients admitted from March 1, 2019, and July 31, 2019 (pre–COVID-19), and March 1, 2020, to July 31, 2020 (COVID-19). The time from arrival to imaging and treatment with thrombolysis or thrombectomy, as continuous variables, were also assessed. Results: Of the 2955 patients who met inclusion criteria, 1491 were admitted during the pre–COVID-19 period and 1464 were admitted during COVID-19, 15% of whom underwent intravenous thrombolysis. Patients treated during COVID-19 were at lower odds of receiving thrombolysis within 60 minutes of arrival (odds ratio, 0.61 [95% CI, 0.38–0.98]; P=0.04), with a median delay in door-to-needle time of 4 minutes (P=0.03). The lower odds of achieving treatment in the Target: Stroke goal persisted after adjustment for all variables associated with earlier treatment (adjusted odds ratio, 0.55 [95% CI, 0.35–0.85]; P\u3c0.01). The delay in thrombolysis appeared driven by the longer delay from imaging to bolus (median, 29 [interquartile range, 18–41] versus 22 [interquartile range, 13–37] minutes; P=0.02). There was no significant delay in door-to-groin puncture for patients who underwent thrombectomy (median, 83 [interquartile range, 63–133] versus 90 [interquartile range, 73–129] minutes; P=0.30). Delays in thrombolysis were observed in the months of June and July. Conclusions: Evaluation for acute ischemic stroke during the COVID-19 period was associated with a small but significant delay in intravenous thrombolysis but no significant delay in thrombectomy time metrics. Taking steps to reduce delays from imaging to bolus time has the potential to attenuate this collateral effect of the pandemic

Immediate Recanalization of Large‐Vessel Occlusions by Tissue Plasminogen Activator Occurs in 28% of Patients Treated in a Mobile Stroke Unit

Background Recanalization of cerebral large‐vessel occlusions (LVOs) by intravenous thrombolysis is infrequent but has been relatively unexplored with ultraearly treatment. We evaluated prehospital treatment with tissue plasminogen activator (tPA) in a mobile stroke unit to explore the recanalization rate in patients with LVOs and its effect on early clinical improvement and long‐term disability. Methods Prospectively collected data were analyzed from Houston mobile stroke unit patients who were treated with tPA and had LVOs identified by either hyperdense arteries on computed tomography or arterial occlusion on computed tomography angiography while on board the mobile stroke unit. The primary outcome was immediate recanalization (IRC), categorized as resolution of LVO on repeat vascular imaging in the emergency department (ED) or on emergent angiography. The secondary outcome was change in National Institutes of Health Stroke Scale from baseline and modified Rankin score at 90 days. Results Sixty‐nine patients with anterior or posterior circulation LVOs were enrolled; the median time from last known normal to tPA bolus was 64.0 minutes (interquartile range, 52.0–89.0). Nineteen patients (28%) had IRC, with 11 based on computed tomography angiography on ED arrival and 8 based on first run of emergent angiography. Median time from tPA bolus to documentation of IRC was 61.0 minutes (interquartile range, 42.0–111.0). IRC was associated with improvement in median National Institutes of Health Stroke Scale from baseline (17.0 [14.0–22.0]) to ED arrival (10.0 [5.5–16.5]) and to 24 hours (4.0 [0.5–10.5]). Of the non‐IRC patients, 41 had recanalization after endovascular thrombectomy and 9 did not receive recanalization. The IRC group, earlier last known normal to tPA bolus, greater baseline National Institutes of Health Stroke Scale, and M1 and M2 middle cerebral artery occlusion locations were independently associated with greater improvement in National Institutes of Health Stroke Scale from baseline to ED arrival. The 90‐day modified Rankin score distribution was best in the IRC group, followed by the delayed recanalization group, and both had significantly less disability than the no recanalization group (P=0.002). Conclusions Recanalization by ED arrival occured in 28% of patients with LVO who received tPA treatment in a mobile stroke unit and results in early clinical improvement and less disability at 90 days

Decline in mild stroke presentations and intravenous thrombolysis during the COVID-19 pandemic: The Society of Vascular and Interventional Neurology Multicenter Collaboration

Background: To evaluate overall ischemic stroke volumes and rates, specific subtypes, and clinical presentation during the COVID-19 pandemic in a multicenter observational study from eight states across US. Methods: We compared all ischemic strokes admitted between January 2019 and May 2020, grouped as; March-May 2020 (COVID-19 period) and March-May 2019 (seasonal pre-COVID-19 period). Primary outcome was stroke severity at admission measured by NIHSS stratified as mild (0-7), moderate [8-14], and severe (\u3e14). Secondary outcomes were volume of large vessel occlusions (LVOs), stroke etiology, IV-tPA rates, and discharge disposition. Results: Of the 7969 patients diagnosed with acute ischemic stroke during the study period, 933 (12 %) presented in the COVID-19 period while 1319 (17 %) presented in the seasonal pre-COVID-19 period. Significant decline was observed in the mean weekly volumes of newly diagnosed ischemic strokes (98 ± 3 vs 50 ± 20,p = 0.003), LVOs (16.5 ± 3.8 vs 8.3 ± 5.9,p = 0.008), and IV-tPA (10.9 ± 3.4 vs 5.3 ± 2.9,p = 0.0047), whereas the mean weekly proportion of LVOs (18 % ±5 vs 16 % ±7,p = 0.24) and IV-tPA (10.4 % ±4.5 vs. 9.9 % ±2.4,p = 0.66) remained the same, when compared to the seasonal pre-COVID-19 period. Additionally, an increased proportion of patients presented with a severe disease (NIHSS \u3e 14) during the COVID-19 period (29.7 % vs 24.5 %,p \u3c 0.025). The odds of being discharged to home were 26 % greater in the COVID-19 period when compared to seasonal pre-COVID-19 period (OR:1.26, 95 % CI:1.07-1.49,p = 0.016). Conclusions: During COVID-19 period there was a decrease in volume of newly diagnosed ischemic stroke cases and IV-tPA administration. Patients admitted to the hospital had severe neurological clinical presentation and were more likely to discharge home