Therapy For Acute Ischemic Stroke Research Articles

Abstract TP181: Endovascular Therapy for Acute Ischemic Stroke With Large Infarct: A Meta Analysis of Randomized Controlled Trials

Background: The efficacy of endovascular thrombectomy (EVT) in patients with large infarct among acute ischemic stroke patients has not been exclusively studied, with conflicting results till date. Objective: We sought to evaluate the outcomes comparing EVT and medical therapy among stroke patients with large infarcts. Methods: We performed a systematic literature search on PubMed, EMBASE, and Clinicaltrial.gov for relevant randomized controlled trials (RCTs) from inception until August 30th, 2023. Odds ratios (OR) were pooled using a random-effect model, and a p-value of <0.05 was considered statistically significant. Results: A total of 3 randomized controlled trials with 1010 patients (509 in EVT and 501 in MT) were included in the analysis. Pooled analysis of primary and secondary endpoints showed that ET was associated with a significantly greater rate of MRS 0-2 (OR, 2.53(95%CI: 1.76-3.64), P<0.001), MRS 0-3 (OR, 1.75(95%CI: 1.28-2.39), P<0.001). ET group of patients were having a significantly higher risk of any intracranial hemorrhage (OR, 2.34(95%CI: 1.53-3.58), P>0.001), and a trend of higher risk of incidence of symptomatic intracranial hemorrhage (OR, 1.83(95%CI: 0.90-3.70), P=0.09) compared to medical therapy. However, the risk of incidence of 90 days mortality (OR, 0.95(95%CI: 0.73-1.24), P=0.71), hemi craniotomy (OR, 0.97(95%CI: 0.45-2.12), P=0.95), and adverse cardiovascular event (OR, 1.68(95%CI: 0.50-5.59), P=0.40) was comparable between ET and MT group. Conclusion: Patients with large infarcts had better functional outcomes with ET than with MT alone. However, intracranial hemorrhage was higher among ET compared with MT group, while 90 days mortality being comparable between both groups of patients.

Abstract WP78: Large Vessel Occlusion Triage and Routing Utilized for Long-Distance Stroke Transports by Emergency Medical Services (LVO TRUST EMS)

Introduction: Endovascular treatment (EVT) is the most effective therapy in acute ischemic stroke (AIS) with large vessel occlusion (LVO) but its practice is limited to comprehensive stroke centers (CSC). Previous studies have suggested that trained Emergency Medical Services (EMS) professionals can successfully detect LVO cases using a validated screening tool. For these cases, direct transfer to CSC bypassing community hospitals could lead to better outcomes. Methods: This is a retrospective cohort study from 01/01/2018-12/31/2022 of patients with suspected stroke transported by EMS providers from 14 community agencies (primarily fire paramedics) in Southeastern Massachusetts (EMS Region V). When stroke was suspected, EMS providers applied the Field Assessment Stroke Triage for Emergency Destination (FAST-ED) score to assess severity. Bypass of local community hospitals for direct transport to CSC was generally considered for patients with FAST-ED ≥4 and approval of the Region V EMS Medical Director, with the goal of early intervention for severe strokes. In addition to standard education on the use of the FAST-ED score, the EMS agencies received annual aggregate performance feedback and individual case feedback (when requested) from the CSC. Data were collected from the Electronic Health Record (EHR) on demographics, comorbidities, final diagnoses, FAST-ED scores, NIHSS and acute treatments. Descriptive statistics were performed to describe the accuracy of diagnosis and rates of treatment. Results: Among 166 triaged patients to go directly to CSC, 57.6% (95/166) were diagnosed with AIS, and 61.1% (58/95) of them were found to have LVO. There was a higher proportion of AIS or intracranial hemorrhage (ICH) in cases with higher FAST-ED scores. Only 23.4% (39/166) of the cases were diagnosed with stroke mimics, primarily related to lower FAST-ED scores. In total, 36.9% of patients with AIS received EVT: thrombectomy with standard window tPA (21.1%) or late presenter tPA (LKW ≥ 4.5 h, 1.1%), and without tPA (14.7%). Conclusions: A diverse group of community-based EMS services in Southeastern Massachusetts using a prehospital tool can identify patients with severe stroke, i.e. AIS due to LVO or ICH, with acceptable diagnostic accuracy.

Abstract TP269: Determining Differences in the Association Between Atrial Fibrillation and Ischemic Stroke Outcomes by Acute Therapy Received

Introduction: Whether the association between atrial fibrillation (AF) and ischemic stroke (IS) outcomes differs by IS therapy is unknown. Hypothesis: AF IS patients will have a worse discharge NIH Stroke Scale (NIHSS) and 90-day modified Rankin Scale (mRS) scores than non-AF, with differences by IS therapy. Methods: We studied a cohort of AF and non-AF IS patients from Johns Hopkins (2020-2023) with IS characteristics and demographics who received acute IS therapy (intravenous tissue plasminogen activator (IVtPA), mechanical thrombectomy (MT), or both). Multivariable regression models were used to examine the association between AF and either NIHSS (continuous or dichotomized at the mean (5)) or mRS (ordinal) separately, with interaction terms for IS therapy as appropriate. Results: Of the 240 patients (mean age 67, 52.5% female, 56.2% Black), 26.2% received IVtPA, 45.8% MT, and 27.9% both. There was no association between AF and NIHSS (β 1.53, 95% CI 0.38-3.4) in the final model, but there were higher odds of an NIHSS > 5 among AF patients (OR 3.46, 95% CI 1.16-10.30). AF patients had an increased odds of a worse mRS (Ordinal OR 2.05, 95% CI 1.14-3.71), but not after adjustment (Ordinal OR 1.07, 95% CI 0.52-2.20). The association between AF and IS outcomes differed by IS therapy (Table 1). AF patients who did not receive MT had a worse NIHSS and higher odds of a one unit increase in mRS, compared to AF patients who received MT (p-interaction 0.07, 0.01 respectively). Conversely, AF patients who received IVtPA had a worse NIHSS, compared to those who did not receive IVtPA (p-interaction 0.07), with essentially no difference in the association between AF and mRS in the final model when considering IVtPA use (p-interaction 0.09). Conclusion: In this study, AF patients had a higher mRS and worse discharge NIHSS versus non-AF, with differences by treatment; not receiving MT was detrimental for AF patients while our found worse outcome with IVtPA may reflect AF-associated treatment delays.

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

Early neurological deterioration (END) after bridging therapy (BT) of acute ischemic stroke (AIS) patients is associated with poor outcomes. We aimed to study the incidence, risk factors and prognosis of END after BT. 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. 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). 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.

Abstract 152: Endovascular Therapy versus Medical Management for Acute Ischemic Stroke With Large Infarct: A Time-Benefit Relationship Analysis

Objective: Recent randomized trials demonstrated the benefit of endovascular thrombectomy for acute ischemic stroke with large infarct. We aimed to characterize the effect of time to treatment on the benefit of endovascular therapy compared to medical management among patients with acute large ischemic stroke. Methods: Analysis the Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients with a Large Infarct Core trial (ANGEL-ASPECT), which was a multicenter, randomized trial at 46 comprehensive stroke centers in China from August 2020 to October 2022. Onset to arterial puncture time (OPT) associated with outcomes of endovascular therapy were analyzed as a category and continuous variable. The primary outcome was favorable outcome (modified Rankin scale 0-3) at 90 days. Secondary outcomes included degree of disability (modified Rankin scale range), symptomatic intracranial hemorrhage, any intracranial hemorrhage, and mortality. Results: Among 455 eligible patients, the median age was 68 years, and median Alberta Stroke Program Early Computed Tomography Score was 3 (interquartile range 3-4). Compared with medical management alone, endovascular therapy plus medical management was associated with higher rates of favorable outcome with OPT within 6 hours (44.4% vs 29.9%, adjusted odds ratio[aOR] 2.78 [95% confidence interval [CI] 1.22-6.32]), 6-12 hours (45.7% vs 29.6%, aOR 2.39 [95% CI 1.21-4.71]), but not in OPT beyond 12 hours (51.6% vs 41.4%, aOR 2.05 [95% CI, 0.88-4.77]). The benefit in favorable outcome became nonsignificant after OPT of 13 hours and 22 minutes. In three OPT intervals, the odds of better disability outcome with endovascular therapy plus medical management than medical management alone were observed; the rates of symptomatic intracranial hemorrhage and mortality were similar, though the rates of any intracranial hemorrhage increased. Conclusion: In patients with large cerebral infarction, endovascular therapy plus medical management was efficacious in improving functional outcomes with acceptable safety in a broad time window of 0 to 24 hours, but greater benefit was observed with earlier treatment. A pooled analysis with larger sample size is needed.

Development and validation of outcome prediction model for reperfusion therapy in acute ischemic stroke using nomogram and machine learning.

To develop logistic regression nomogram and machine learning (ML)-based models to predict 3-month unfavorable functional outcome for acute ischemic stroke (AIS) patients undergoing reperfusion therapy. Patients undergoing reperfusion therapy (intravenous thrombolysis and/or endovascular treatment) were prospectively recruited. Unfavorable outcome was defined as 3-month modified Rankin Scale (mRS) score 3-6. The independent risk factors associated with unfavorable outcome were obtained by regression analysis and included in the prediction model. The performance of nomogram was assessed by the area under the curve (AUC), calibration curve, and decision curve analysis (DCA). ML models were compared with nomogram using AUC; the generalizability of all models was ascertained in an external cohort. A total of 505 patients were enrolled, with 256 in the model construction, and 249 in the external validation. Five variables were identified as prognostic factors: baseline NIHSS, D-dimer level, random blood glucose (RBG), blood urea nitrogen (BUN), and systolic blood pressure (SBP) before reperfusion. The AUC values of nomogram were 0.865, 0.818, and 0.779 in the training set, test set, and external validation, respectively. The calibration curve and DCA indicated appreciable reliability and good net benefits. The best three ML models were extra trees (ET), CatBoost, and random forest (RF) models; all of them showed favorable discrimination in the training cohort, and confirmed in the test and external sets. Baseline NIHSS, D-dimer, RBG, BUN, and SBP before reperfusion were independent predictors for 3-month unfavorable outcome after reperfusion therapy in AIS patients. Both nomogram and ML models showed good discrimination and generalizability.

Multicenter exploration of tenecteplase transition factors: A quantitative analysis

BackgroundTenecteplase (TNK) is gaining recognition as a novel therapy for acute ischemic stroke (AIS). Despite TNK offering a longer half-life, time and cost saving benefits and comparable treatment and safety profiles to Alteplase (ALT), the adoption of TNK as a treatment for AIS presents challenges for hospital systems. ObjectiveIdentify barriers and facilitators of TNK implementation at acute care hospitals in Texas. MethodsThis prospective survey used open-ended questions and Likert statements generated from content experts and informed by qualitative research. Stroke clinicians and nurses working at 40 different hospitals in Texas were surveyed using a virtual platform. ResultsThe 40 hospitals had a median of 34 (IQR 24.5–49) emergency department beds and 42.5 (IQR 23.5–64.5) inpatient stroke beds with 506.5 (IQR 350–797.5) annual stroke admissions. Fifty percent of the hospitals were Comprehensive Stroke Centers, and 18 (45 %) were solely using ALT for treatment of eligible AIS patients. Primary facilitators to TNK transition were team buy-in and a willingness of stroke physicians, nurses, and pharmacists to adopt TNK. Leading barriers were lack of clinical evidence supporting TNK safety profile inadequate evidence supporting TNK use and a lack of American Heart Association guidelines support for TNK administration in all AIS cases. ConclusionUnderstanding common barriers and facilitators to TNK adoption can assist acute care hospitals deciding to implement TNK as a treatment for AIS. These findings will be used to design a TNK adoption Toolkit, utilizing implementation science techniques, to address identified obstacles and to leverage facilitators.

Safety Profile of Intra-Arterial Tirofiban as a Rescue Therapy during Mechanical Thrombectomy in Acute Ischemic Stroke

Abstract Purpose This article studies the safety profile and role of intra-arterial (IA) tirofiban as a rescue therapy in acute ischemic stroke (AIS) patients undergoing mechanical thrombectomy. Methods This is a retrospective observational study conducted among AIS patients with large vessel occlusion (LVO) eligible for endovascular revascularization and in whom IA tirofiban is given as rescue therapy. If the target vessel shows reocclusion following initial recanalization, flow limiting or significant residual stenosis after thrombectomy, or requires balloon angioplasty or stenting, IA tirofiban at a dose of 0.4 μg/kg/min was administered through the microcatheter in the target vessel followed by intravenous infusion of 0.1 μg/kg/min. The primary safety measure of the study was the incidence of symptomatic hemorrhage. Results The total number of patients in the study group was 82, 36 were in the tirofiban group and 46 were in the non-tirofiban group. Immediate successful reperfusion was achieved in 31 patients (86.1%) and 41 patients (89%) in the tirofiban and non-tirofiban groups, respectively. Note that 19.4 and 25% of patients in the tirofiban group required adjunct techniques of angioplasty and stenting, respectively. Also, 2.7% patient in the tirofiban group had a symptomatic hemorrhage, while 8.7% in the non-tirofiban group had symptomatic intracranial hemorrhage. On multinomial logistic regression, history of transient ischemic attack, truncal occlusion and watershed infarct pattern predicted the usage of IA tirofiban during mechanical thrombectomy. Conclusion Usage of IA tirofiban with or without adjunct techniques as a rescue therapy during mechanical thrombectomy in LVO improved recanalization rates without increasing the risk of symptomatic hemorrhage.

Allogeneic Stem Cell Therapy for Acute Ischemic Stroke

Cell therapy is a promising treatment approach for stroke and other diseases. However, it is unknown whether MultiStem (HLCM051), a bone marrow-derived, allogeneic, multipotent adult progenitor cell product, has the potential to treat ischemic stroke. To assess the efficacy and safety of MultiStem when administered within 18 to 36 hours of ischemic stroke onset. The Treatment Evaluation of Acute Stroke Using Regenerative Cells (TREASURE) multicenter, double-blind, parallel-group, placebo-controlled phase 2/3 randomized clinical trial was conducted at 44 academic and clinical centers in Japan between November 15, 2017, and March 29, 2022. Inclusion criteria were age 20 years or older, presence of acute ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score of 8-20 at baseline), confirmed acute infarction involving the cerebral cortex and measuring more than 2 cm on the major axis (determined with diffusion-weighted magnetic resonance imaging), and a modified Rankin Scale (mRS) score of 0 or 1 before stroke onset. Data analysis was performed between May 9 and August 15, 2022. Patients were randomly assigned to either intravenous MultiStem in 1 single unit of 1.2 billion cells or intravenous placebo within 18 to 36 hours of ischemic stroke onset. The primary end points were safety and excellent outcome at day 90, measured as a composite of a modified Rankin Scale (mRS) score of 1 or less, a NIHSS score of 1 or less, and a Barthel index score of 95 or greater. The secondary end points were excellent outcome at day 365, mRS score distribution at days 90 and 365, and mRS score of 0 to 1 and 0 to 2 at day 90. Statistical analysis of efficacy was performed using the Cochran-Mantel-Haenszel test. This study included 206 patients (104 received MultiStem and 102 received placebo). Their mean age was 76.5 (range, 35-95) years, and more than half of patients were men (112 [54.4%]). There were no between-group differences in primary and secondary end points. The proportion of excellent outcomes at day 90 did not differ significantly between the MultiStem and placebo groups (12 [11.5%] vs 10 [9.8%], P = .90; adjusted risk difference, 0.5% [95% CI, -7.3% to 8.3%]). The frequency of adverse events was similar between treatment groups. In this randomized clinical trial, intravenous administration of allogeneic cell therapy within 18 to 36 hours of ischemic stroke onset was safe but did not improve short-term outcomes. Further research is needed to determine whether MultiStem therapy for ischemic stroke has a beneficial effect in patients who meet specific criteria, as indicated by the exploratory analyses in this study. ClinicalTrials.gov Identifier: NCT02961504.

Efficacy and Safety of Intensive Blood Pressure Lowering After Reperfusion Therapy in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis

The objective of this study is to comprehensively examine the available data on the efficacy and safety of intensive blood pressure lowering (IBPL) compared to standard blood pressure control (SBPC) in patients with acute ischemic stroke following reperfusion therapy. A comprehensive search was conducted using 4 databases, including PubMed, Cochrane, Embase, and Web of Science to collect relevant articles from inception to December 2023. The endpoints were the condition of the patient measured by the modified Rankin scale (mRS, range value from 0 [no symptoms] to 6 [death]) at 90days, symptomatic intracranial hemorrhage, death within 90days, recurrent ischemic stroke, and intracranial hemorrhage (ICH). Seven eligible studies involving 4499 participants (2218 patients in IBPL group and 2281 patients in SBPC group) were included in the analysis. Both groups demonstrated similar baseline characteristics. Within the endovascular therapy (EVT) subgroup, the IBPL group exhibited worse mRS than in SBPC group. After EVT, different IBPL targets showed worse outcomes in the mRS for the SBP <140mmHg and SBP <120mmHg subgroups, with no difference between IBPL and SBPC groups in the SBP <130mmHg subgroup. In the intravenous thrombolysis subgroup, although the IBPL group exhibited less ICH, the long-term functional outcomes were not improved significantly. The IBPL group exhibited a less favorable functional outcome after EVT. Moreover, no worse functional outcomes were noticed in the SBP <130mmHg subgroup after EVT. However, the functional outcome was similar after intravenous thrombolysis.

Provider Care Segregation and Hospital-Region Racial Disparities in the United States for Acute Ischemic Stroke and Endovascular Therapy Outcomes.

Reasons for racial disparities in the use and outcomes of endovascular treatment (ET) are not known. We examined patterns in care segregation for acute ischemic stroke (AIS) in the United States, and outcomes of segregation of care after ET. We used deidentified Medicare data sets to identify AIS admissions between January 1, 2016 and December 31, 2019, using validated International Classification of Diseases, Tenth Revision (ICD-10) codes. For AIS, we calculated (1) the proportion of White patients at the hospital, (2) the proportional difference in the proportion of White patients between hospital patients and the county, and (3) provider care segregation by the dissimilarity index for ET cases. Using unadjusted and adjusted multilevel logistic models, we examined associations between measures of segregation and outcomes of discharge home, inpatient mortality, and 30-day mortality. The mean proportional difference in the proportion of White patients comparing hospitalized patients with AIS to the county race distribution was 0.015 (SD, 0.219) at the hospital level. For ET, the mean proportional difference in the proportion of White patients comparing patients receiving ET to the county race distribution was much higher, at 0.146 (SD, 0.374). The dissimilarity index for ET providers was high, with a mean of 0.48 (SD, 0.29) across all hospitals. Black patients with AIS (compared with White patients) had reduced odds of discharge home, inpatient mortality, and 30-day mortality. In this national study with contemporary data in the endovascular era of AIS treatment, we found substantial evidence for segregation of care in the United States, not for only AIS in general but also especially for ET.

Associations between NIHSS sub-item scores and prognosis and intracranial hemorrhage after endovascular therapy for acute anterior circulation ischemic stroke.

The relationship between sub-item scores on the National Institutes of Health Stroke Scale (NIHSS) scores and prognosis and intracranial hemorrhage in patients with acute ischemic stroke undergoing endovascular treatment (EVT) has been insufficiently studied. The aim of this study was to investigate the correlation between NIHSS sub-item scores, prognosis, and intracranial hemorrhage. This study included patients with acute anterior circulation ischemic stroke undergoing EVT between February 2019 and April 2022. The outcomes included functional independence, defined as a modified Rankin Scale (mRS) score ≤ 2 at 3 months after EVT, intracranial hemorrhage within 24 h after EVT, and mortality within 3 months. A multivariate regression analysis was performed, including NIHSS sub-item scores and other adjusted variables. A total of 568 patients were enrolled. Of the 568 patients, 239 (45%) achieved functional independence at 3 months after EVT. The median age in this group was 63 years (IQR 52-69) and 176 (73.6%) were male patients. Intracranial hemorrhage within 24 h after EVT occurred in 170 (30%) patients. The median age in this group was 65 years (IQR 56-71) and 105 (61.8%) were male patients. In a multivariate analysis adjusted for age, gender, and factors with a value of p of <0.05, the NIHSS limb movement sub-item score was strongly associated with prognosis at 3 months (OR 0.833, 95% CI 0.758-0.915) and intracranial hemorrhage within 24 h after EVT (OR 1.161, 95% CI 1.037-1.300). Higher limb movement sub-item scores on the NIHSS were independently associated with a poorer prognosis at 3 months and a higher rate of intracranial hemorrhage within 24 h after EVT among patients with acute anterior circulation ischemic stroke.

Early Antithrombotic Therapy in Acute Ischemic Stroke

Early Antithrombotic Therapy in Acute Ischemic Stroke

Functional network reorganization after endovascular thrombectomy in patients with anterior circulation stroke

BackgroundEndovascular thrombectomy has been confirmed to be an effective therapy for acute ischemic stroke (AIS). However, how functional brain networks reorganize after restoration of blood supply in AIS patients, and whether the degree of reperfusion associates with functional network changes remains unclear. MethodsResting-state fMRI data were collected from 43 AIS patients with anterior circulation occlusion after thrombectomy and 37 healthy controls (HCs). Both static and dynamic functional connectivity (FC) within four advanced functional networks including dorsal attention network (DAN), ventral attention network (VAN), executive control network (ECN) and default mode network (DMN), were calculated and compared between post-thrombectomy patients and HCs, and between two subgroups of post-thrombectomy patients with different reperfusion conditions. ResultsAs compared to HCs, patients showed significant differences in static FC of four functional networks, and in dynamic FC of DAN, ECN and DMN. Furthermore, patients with better reperfusion conditions exhibited increased static FC with precuneus, and altered dynamic FC within precuneus. Moreover, these alterations were associated with clinical assessments of stroke severity and functional recovery in post-thrombectomy patients. ConclusionsCollectively, these findings may provide the potential imaging markers for assessment of thrombectomy efficacy and help establish the specific rehabilitation treatments for post-thrombectomy patients.

“Hemorrhagic Transformation Following Thrombolytic Therapy in Acute Ischemic Stroke: A Case Series of 5 Patients”

Stroke stands as a global health menace, causing substantial disability and mortality. Timely intervention, specifically within the critical "Golden Hour" following acute ischemic stroke, is imperative. Thrombolytic agents like tissue plasminogen activators (tPA) are pivotal for clot dissolution and blood flow restoration, yet their use introduces the risk of hemorrhagic transformation (HTF).In a recent case series involving five patients receiving thrombolytic therapy for acute ischemic stroke, we illuminate the occurrence of post-treatment HTF, its clinical ramifications, and the intricate challenges in its management. Early intervention in acute ischemic stroke aims to safeguard at-risk brain tissue, with thrombolytic therapy, notably tPA, serving as a primary treatment avenue. However, the associated risk of HTF hovers around 30%–35%, influenced by factors like age, comorbidities, and infarct size. The vulnerable ischemic penumbra, marked by a compromised blood-brain barrier and free radical generation, is particularly susceptible. Treatment decisions, guided by the National Institutes of Health Stroke Scale (NIHSS), pivot on stroke severity assessment, emphasizing the need for vigilant post-treatment monitoring. In conclusion, navigating the delicate balance between the benefits of early thrombolysis and the risks of HTF remains a persistent challenge in optimizing outcomes for acute ischemic stroke patients.

Diagnostic accuracy of dual-energy computed tomography in the diagnosis of neurological complications after endovascular treatment of acute ischaemic stroke: a systematic review and meta-analysis.

To investigate dual-energy computed tomography's (DECT) diagnostic performance in detecting neurological complications following endovascular therapy (EVT) of acute ischaemic stroke (AIS). We performed the literature search using Web of Science, Scopus, PubMed, EBSCO, and Science Direct databases for published related studies. The selected studies estimated the validity of DECT in the detection of neurological complications after EVT for AIS. Study quality assessment was performed utilizing the Quality of Diagnostic Accuracy Studies-2 Tool. Our meta-analysis calculated the pooled sensitivity, negative likelihood ratio, specificity, and positive likelihood ratio for each detected complication. The summary receiver operating characteristics (sROC) curve was utilized to estimate the area under the curve (AUC). Of 22 studies, 21 were included in the quantitative synthesis. In the detection of intracerebral haemorrhage (ICH), DECT pooled overall sensitivity and specificity were 69.9% (95% CI, 44.5%-86.8%) and 100% (95% CI, 92.1%-100%); whereas, in the detection of ischaemia, they were 85.9% (95% CI, 80.4%-90%) and 90.7% (95% CI, 87%-93.5%), respectively. On the sROC curve, AUC values of 0.954 and 0.952 were recorded for the detection of ICH and ischaemia, respectively. DECT demonstrated high accuracy and specificity in the detection of neurological complications post-endovascular treatment of AIS. However, further prospective studies with a standardized reference test and a larger sample size are recommended to support these findings. DECT is a rapid and valid imaging tool for the prediction of ICH and cerebral ischaemia after the EVT of AIS.

Cost-effectiveness of endovascular therapy for acute stroke with a large ischemic region in Japan: impact of the Alberta Stroke Program Early CT Score on cost-effectiveness

BackgroundAlthough randomized clinical trials (RCTs) demonstrated short-term benefits of endovascular therapy (EVT) for acute ischemic stroke (AIS) with a large ischemic region, little is known about the long-term cost-effectiveness or...

Specific inhibition on PAI-1 reduces the dose of Alteplase for ischemic stroke treatment

Administration of recombinant tPA (rtPA, or trade name Alteplase®) is an FDA-approved therapy for acute ischemic stroke (AIS), but poses the risk of hemorrhagic complications. Recombinant tPA can be rapidly inactivated by the endogenous inhibitor, plasminogen activator inhibitor 1 (PAI-1). In this work, we study a novel treatment approach that combines a PAI-1 inhibitor, PAItrap4, with a reduced dose of rtPA to address the hemorrhagic concern of rtPA. PAItrap4 is a highly specific and very potent protein-based inhibitor of PAI-1, comprising of a variant of uPA serine protease domain, human serum albumin, and a cyclic RGD peptide. PAItrap4 efficiently targets and inhibits PAI-1 on activated platelets, and also possesses a long half-life in vivo. Our results demonstrate that PAItrap4 effectively counteracts the inhibitory effects of PAI-1 on rtPA, preserving rtPA activity based on amidolytic and clot lysis assays. In an in vivo murine stroke model, PAItrap4, together with low-dose rtPA, enhances the blood perfusion in the stroke-affected areas, reduces infarct size, and promotes neurological recovery in mice. Importantly, such treatment does not increase the amount of cerebral hemorrhage, thus reducing the risk of cerebral hemorrhage. In addition, PAItrap4 does not compromise the normal blood coagulation function in mice, demonstrating its safety as a therapeutic agent. These findings highlight this combination therapy as a promising alternative for the treatment of ischemic stroke, offering improved safety and efficacy.

General anesthesia versus nongeneral anesthesia during endovascular therapy for acute ischemic stroke: A systematic review and meta-analysis.

This study compares the safety and efficacy of general anesthesia (GA) and nongeneral anesthesia (non-GA) on functional outcomes in patients receiving endovascular therapy for ischemic stroke. All available studies on the anesthetic management of patients with acute ischemic stroke in PubMed, the Cochrane Central Register of Controlled Trials, and Embase were included. We also compared the clinical outcomes in the studies with subgroup analyses of the occlusion site (anterior vs. posterior circulation) and preretriever group versus retriever group. Functional independence, mortality, successful recanalization, hemodynamic instability, intracerebral hemorrhage, and respiratory complications were considered primary or secondary outcomes. A total of 24,606 patients in 60 studies were included. GA had a lower risk of 90-day functional independence (OR=0.67, 95% CI 0.58 to 0.77), higher risk of 90-day mortality (OR=1.29; 95% CI 1.15 to 1.45), and successful reperfusion (OR=1.18; 95% CI 1.94 to 6.82). However, there were no differences in functional independence and mortality between GA and non-GA at 90 days after the procedure. The study shows poorer results in the GA group, which may be due to the inclusion of nonrandomized studies. However, analysis of the RCTs suggested that the outcomes do not differ between the two groups (GA vs. non-GA). Thus, general anesthesia is as safe as nongeneral anesthesia under standardized management.

Cost-effectiveness analysis of CYP2C19 genotype-guided antiplatelet therapy for patients with acute minor ischemic stroke and high-risk transient ischemic attack in China.

The study aimed to estimate the cost-effectiveness of CYP2C19 genotype-guided antiplatelet therapy using cilostazol and ticagrelor as an alternative to clopidogrel, compared to conventional antiplatelet therapy with clopidogrel and aspirin. A 90-day decision tree and 30-year Markov model were employed to assess the costs and quality-adjusted life years (QALYs) of personalized antiplatelet therapy for patients with minor ischemic stroke and high-risk transient ischemic attack, compared to conventional antiplatelet therapy in the Chinese healthcare system. The primary outcome was the incremental cost-effectiveness ratio (ICER). The data sources included clinical trials, published literature, official documents and local prices. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to confirm the robustness of the findings. The base-case analysis indicated that the CYP2C19 genotype-guided antiplatelet strategy was cost-effective, and cilostazol group and ticagrelor group yielded an ICER of 3327.40 US dollars (USD)/QALY and 3426.92 USD/QALY, respectively, which were less than threshold. The one-way sensitivity analysis showed the results were robust, where the most sensitive parameter was the disability distribution in the modified Rankin scale 3-5. The probabilistic analysis showed that the CYP2C19 genotype-guided antiplatelet therapy with either cilostazol or ticagrelor was 100% cost-effective under the willingness-to-pay threshold. CYP2C19 genotype-guided antiplatelet therapy usingcilostazol and ticagrelor as an alternative to clopidogrel appeared to be more cost-effective than conventional antiplatelet therapy for acute minor ischemic stroke and high-risk transient ischemic attack patients over 30 years in China.