Adusumilli, Gautam

Background Collateral blood flow markers have been associated with outcomes after thrombectomy in patients presenting with acute ischemic stroke due to large vessel occlusion (AIS-LVO). Hypoperfusion intensity ratio (HIR), a metric reflecting tissue level collaterals, is one such marker with the potential to delineate patients who do and do not do well after thrombectomy. We determined if HIR correlated with successful reperfusion after thrombectomy. Methods Using Nested Knowledge, we screened literature for studies comparing patients with favorable versus unfavorable HIR, distinguished by a cutoff of 0.4, who underwent thrombectomy triage. The primary outcome was reperfusion success, as measured by thrombolysis in cerebral infarction ≥2b and secondary outcomes included rate of symptomatic intracranial hemorrhage, mortality at 90 days, and modified Rankin scale scores 0–2 at 90 days. A random effects model was used to compute pooled prevalence rates and their corresponding 95% confidence intervals (CI). Results Three studies with 973 patients, 496 with favorable HIR, and 477 with unfavorable HIR were included in this meta-analysis. The odds of reperfusion success were not significantly different between patients who had favorable versus unfavorable HIR (OR 0.96, 95% CI: 0.31–3.04) across two of the studies. Analysis of the remaining outcome variables was precluded by significant heterogeneity in data element reporting. Conclusions This meta-analysis was considerably limited by heterogeneity. Future meta-analyses on this topic, and other topics in the field of neurointervention would benefit from improved harmonization of study design and data element reporting.

Background Limited randomized controlled trials (RCTs) have been performed comparing endovascular thrombectomy (EVT) to medical therapy (MEDT) for acute ischemic stroke with extensive baseline ischemic injury (AIS-EBI). We conducted a systematic review and meta-analysis of RCTs reporting EVT for AIS-EBI. Methods Using the Nested Knowledge AutoLit software, we conducted a systematic literature review from inception to 12 February 2023 within Web of Science, Embase, Scopus, and PubMed databases. Results of the TESLA trial were included on 10 June 2023. We included RCTs that compared EVT to MEDT for AIS with large ischemic core volume. The primary outcome of interest was a modified Rankin Score (mRS) 0-2. Secondary outcomes of interest included early neurological improvement (ENI), mRS 0-3, thrombolysis in cerebral infarction (TICI) 2b-3, symptomatic intracranial hemorrhage (sICH), and mortality. A random-effects model was used to calculate risk ratios (RRs) and their corresponding 95% confidence intervals (CIs). Results We included four RCTs with 1310 patients, 661 of whom underwent EVT and 649 of whom were treated with MEDT. EVT was associated with greater rates of mRS 0-2 (RR = 2.33, 95% CI = 1.75–3.09; P -value < 0.001), mRS 0-3 (RR = 1.68, 95% CI = 1.33–2.12; P -value < 0.001), and ENI (RR = 2.24, 95% CI = 1.55–3.24; P -value < 0.001). Rates of sICH (RR = 1.99, 95% CI = 1.07–3.69; P -value = 0.03) were greater in the EVT group. Mortality (RR = 0.98, 95% CI = 0.83–1.15; P -value = 0.79) was comparable between the EVT and MEDT groups. The rate of successful reperfusion in the EVT group was 79.9% (95% CI = 75.6–83.6). Conclusions Although the rate of sICH was greater in the EVT group, EVT conferred a greater clinical benefit to MEDT for AIS-EBI based on available RCTs.

ImportancePrevious randomized clinical trials (RCTs) have supported the use of endovascular therapy (EVT) in late-window acute ischemic stroke (AIS; 6-24 hours). However, little is known about the use of EVT in very late-window AIS (&amp;gt;24 hours).ObjectiveTo examine outcomes following EVT for very late-window AIS.Data SourcesA systematic review of the English language literature was conducted using Web of Science, Embase, Scopus, and PubMed to search for articles published from database inception until December 13, 2022.Study SelectionThis systematic review and meta-analysis included published studies regarding very late-window AIS treated with EVT. Multiple reviewers screened studies, and an extensive manual search of the references of included articles was performed to identify any missed articles. Of the 1754 initially retrieved studies, 7 published between 2018 and 2023 were ultimately included.Data Extraction and SynthesisData were extracted independently by multiple authors and evaluated for consensus. Data were pooled using a random-effects model. This study is reported per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guideline, and the protocol was prospectively registered with PROSPERO.Main Outcomes and MeasuresThe primary outcome of interest was functional independence, as assessed with 90-day modified Rankin Scale (mRS) scores (0-2). Secondary outcomes included thrombolysis in cerebral infarction (TICI) scores (2b-3 or 3), symptomatic intracranial hemorrhage (sICH), 90-day mortality, early neurological improvement (ENI), and early neurological deterioration (END). Frequencies and means were pooled with the corresponding 95% CIs.ResultsThis review included 7 studies involving a total of 569 patients. The mean baseline National Institutes of Health Stroke Scale score was 13.6 (95% CI, 11.9-15.5), and the mean Alberta Stroke Program Early CT Score was 7.9 (95% CI, 7.2-8.7). The mean time from last known well and/or onset to puncture was 46.2 hours (95% CI, 32.4-65.9 hours). Frequencies for the primary and secondary outcomes were 32.0% (95% CI, 24.7%-40.2%) for functional independence (90-day mRS scores of 0-2) and 81.9% (95% CI, 78.5%-84.9%) for TICI scores of 2b to 3, 45.3% (95% CI, 36.6%-54.4%) for TICI scores of 3, 6.8% (95% CI, 4.3%-10.7%) for sICH, and 27.2% (95% CI, 22.9%-31.9%) for 90-day mortality. In addition, frequencies were 36.9% (95% CI, 26.4%-48.9%) for ENI and 14.3% (95% CI, 7.1%-26.7%) for END.Conclusions and RelevanceIn this review, EVT for very late-window AIS was associated with favorable frequencies of 90-day mRS scores of 0 to 2 and TICI scores of 2b to 3 and with low frequencies of 90-day mortality and sICH. These results suggest that EVT may be safe and associated with improved outcomes for very late-window AIS, although RCTs and prospective, comparative studies are needed to determine which patients may benefit from very late intervention.

Introduction Mechanical thrombectomy (MT) is the standard of care in eligible patients presenting with acute ischemic stroke (AIS). The question of whether intravenous thrombolysis (IVT) improves outcomes in conjunction with MT remains unanswered. We performed a systematic review and meta-analysis of published randomized controlled trials (RCT) to explore outcomes of MT with and without IVT. Methods Following the PRISMA guidelines, a systematic literature review of the English language literature was conducted using PubMed, Embase, Web of science, and Scopus. Outcomes of interest included 90-day modified Rankin Scale (mRS) 0–2, thrombolysis in cerebral infarction (TICI) score 2b-3, symptomatic intracranial hemorrhage (sICH), distal embolization, and mortality. We calculated pooled risk ratios (RRs) and their corresponding 95% confidence intervals (CI). Results Six RCTs with 2334 patients compared outcomes of patients treated with MT alone and MT with IVT. Both treatments resulted in comparable rates of mRS 0–2 (RR = 0.96, 95% CI = 0.88–1.04; p -value = 0.282), sICH (RR = 0.80, 95% CI = 0.55–1.17; p -value = 0.253), mortality at 90-days (RR = 1.06, 95% CI = 0.88–1.28; p -value = 0.529), and distal embolization (RR = 1.10, 95% CI = 0.79–1.52; p -value = 0.572). MT alone was associated with a lower rate of TICI 2b-3 compared to MT with IVT (RR = 0.96, 95% CI = 0.93–0.99; p -value = 0.006). Conclusions In this meta-analysis of six RCTs, MT alone was comparable to MT plus IVT for mRS 0–2, sICH, mortality, and distal embolization; however, MT alone resulted in lower rates of TICI 2b-3. Further trials are needed to determine which patient populations benefit from MT plus IVT and to increase the power of future meta-analyses.

Background There is limited evidence on the optimal endovascular strategy for treatment of distal medium-vessel occlusions (DMVO). The low-profile Tigertriever 13 stent-triever shows early promise as an adaptable device that can navigate the distal vasculature without increasing complication risk in DMVO. Methods Using Nested Knowledge, we screened literature for RCTs and cohort studies on the endovascular treatment of DMVO. The primary outcome was reperfusion success, as measured by thrombolysis in cerebral infarction (TICI) ≥ 2b and secondary outcomes included rate of symptomatic intracranial hemorrhage (sICH), mortality at 90 days, and modified Rankin scale (mRS) scores 0–2 at 90 days. A random-effects model was used to compute pooled prevalence rates and their corresponding 95% confidence intervals (CI). Results Eleven studies with 1402 patients, 167 patients treated by Tigertriever 13 and 1235 patients treated by other devices, were included in the meta-analysis. The rate of reperfusion success was similar in patients treated by Tigertriever 13 (83.2% [95% CI: 71.5–96.7%]) versus other devices (81.6% [95% CI: 75.3–88.4%], p > 0.05). The rate of sICH was also similar in patients treated by Tigertriever 13 (7.2% [95% CI: 4.1–12.5%]) versus other devices (6.9% [95% CI: 5.5–8.8%]). There was significant heterogeneity in the reporting of mortality and mRS. Conclusions Tigertriever 13 had similar rates of reperfusion success and sICH as other devices used for the treatment of DMVO. Heterogeneity in data element reporting prevented further analyses. Further studies evaluating Tigertriever 13 and other potential devices in DMVO should attempt to harmonize data element reporting.

Background Previous randomized controlled trials (RCTs) and meta-analyses were underpowered to demonstrate the superiority of endovascular thrombectomy (EVT) over medical therapy (MEDT) in the treatment of acute ischemic stroke due to large vessel occlusion of the posterior circulation (PC-LVO). We performed an updated systematic review and meta-analysis after the publication of the BAOCHE and ATTENTION trials to determine whether EVT can benefit patients presenting with PC-LVO. Methods Using Nested Knowledge, we screened literature for RCTs on EVT in PC-LVO. The primary outcome was 90-day modified Rankin Scale (mRS) score 0–3, and secondary outcomes included 90-day mRS score 0–2, 90-day mortality, and rate of symptomatic intracranial hemorrhage (sICH). A random-effects model was used to compute rate ratios (RRs) and their corresponding 95% confidence intervals (CIs). Results Four RCTs with 988 patients, 556 patients in the EVT arm and 432 patients in the MEDT arm, were included in the meta-analysis. EVT resulted in significantly higher rates of mRS score 0–3 (RR=1.54; 95% CI 1.16 to 2.04; P=0.002) and functional independence (RR=1.83; 95% CI 1.08 to 3.08; P=0.024), and lower rates of mortality (RR=0.76; 95% CI 0.65 to 0.90; P=0.002) at 90-day follow-up compared with MEDT alone. However, EVT patients had higher rates of sICH (RR=7.48; 95% CI 2.27 to 24.61; P<0.001). Conclusions EVT conferred significant patient benefit over MEDT alone in the treatment of PC-LVO. Future studies should better define patients for whom EVT is futile and determine factors that contribute to higher rates of sICH.

Background Previous studies comparing a direct aspiration first pass technique (ADAPT) and stent retrievers have inconsistent methodologies and data reporting, limiting the ability to accurately assimilate data from different studies that would inform treatment of acute ischemic stroke (AIS) treatment. Objective To conduct a systematic review to discuss and compare the findings of all relevant meta-analysis studies comparing the efficacy of the ADAPT and stent retriever techniques. Methods The study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), where meta-analyses comparing the efficacy of the ADAPT technique and stent retrievers in the treatment of AIS were included. We extracted all relevant data from the included studies and assessed the quality of the included meta-analyses using the Assessment of Multiple Systematic Review (AMSTAR-2). Results Seven relevant studies met our inclusion criteria and were suitable for the qualitative synthesis. All included studies obtained data from randomized controlled trials (RCTs) and observational investigations (including levels II, III, and IV). At the same time, none of them used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) for quality assessment. In accordance with AMSTAR-2, two studies were rated ‘high’, while the other five were rated ‘moderate’. Conclusions Present evidence is insufficient to clarify the superiority of one modality over the other. Further RCTs on this comparison must be conducted prior to designing further meta-analyses or making conclusive interpretations. Procedure duration and cost should be taken into consideration for any future studies.

Background Endovascular thrombectomy (EVT) is an effective treatment for acute ischemic stroke attributable to the anterior circulation large‐vessel occlusion. Randomized trials of patients with posterior circulation large‐vessel occlusion (PC‐LVO) have failed to show a benefit of EVT over medical therapy (MEDT). We performed a systematic review and meta‐analysis to understand better whether EVT is beneficial for PC‐LVO. Methods Using the Nested Knowledge AutoLit living review platform, we identified randomized control trials and prospective studies that reported functional outcomes in patients with PC‐LVO treated with EVT versus MEDT. The primary outcome variable was 90‐day modified Rankin scale score of 0 to 3, and secondary outcome variables included 90‐day modified Rankin scale score of 0 to 2, 90‐day mortality, and rate of symptomatic intracranial hemorrhage. A separate random effects model was fit for each outcome measure to calculate pooled odds ratios. Results Three studies with 1248 patients, 860 in the EVT arm and 388 in the MEDT arm, were included in the meta‐analysis. The favorable outcome rate (modified Rankin scale score of 0–3) in patients undergoing EVT was 39.9% (95% CI, 30.6%–50.1%) versus 24.5% in patients undergoing MEDT (95% CI, 9.6%–49.8%). Patients undergoing EVT had higher modified Rankin scale score of 0 to 2 rates (31.8% [95% CI, 25.7%–38.5%] versus 19.7% [95% CI, 7.4%–42.7%]) and lower mortality (42.1% [95% CI, 35.9%–48.6%] versus 52.8% [95% CI, 33.3%–71.5%]) compared with patients undergoing MEDT, but neither result was statistically significant. Patients undergoing EVT were more likely to develop symptomatic intracranial hemorrhage (odds ratio, 10.36; 95% CI, 3.92–27.40). Conclusions EVT treatment of PC‐LVO trended toward superior functional outcomes and reduced mortality compared with MEDT despite a trend toward increased symptomatic intracranial hemorrhage in patients undergoing EVT. Existing randomized and prospective studies are insufficiently powered to demonstrate a benefit of EVT over MEDT in patients with PC‐LVO.