Recanalization Time Research Articles

Platelet membrane coated r-SAK to improve thrombolytic efficacy by targeting thrombus

Abstract Background Thrombolytic therapy is one of the most effective treatments to achieve rapid thrombus clearance and recanalization of blocked vessels in thrombotic diseases. However, the application of thrombolytic strategy has been limited due to unsatisfied thrombolytic efficacy, relatively higher bleeding complications, and consequently restricted indications.[1] With the development of nanotechnology and biotechnology, platelet membrane nanoparticles have been developed to enable the targeted delivery of thrombolytic agents to local thrombus sites.[2] Recombinant staphylokinase (r-SAK) is a third-generation thrombolytic agent produced by genetic engineering technology. In this study, platelet membrane coated r-SAK (PLT-r-SAK) was constructed, and its thrombolytic efficacy was evaluated in in-vitro and in-vivo experiments. Purpose We aimed to construct a thrombus-targeting agent of PLT-r-SAK and investigate its thrombolytic efficacy. Methods PLT-r-SAK was prepared by encapsulating r-SAK into platelet membrane vesicles using a membrane extrusion method. An in-vitro thrombolytic experiment was performed to examine the thrombolytic efficacy of PLT-r-SAK, and a totally occluded femoral artery thrombosis model of rabbit was developed to evaluate the in-vivo thrombolytic efficacy of PLT-r-SAK. The changes in femoral artery pressure were adopted to assess the vessel opening status. Besides, the effect of the antiplatelet drugs on the thrombolytic efficacy of PLT-r-SAK was explored. Finally, near-infrared fluorescence imaging system was used to verify the thrombus-targeting effect of PLT-r-SAK. Results PLT-r-SAK was firstly constructed, which exhibited a uniformly dispersed spherical morphology with a diameter of 185.8 ± 1.5 nm and a zeta potential of -26.1 ± 0.8 mV. In the in-vitro animal experiment, the thrombolysis rate of PLT-r-SAK was significantly higher than that of the same (low) dose and 4-fold (high) dose r-SAK (Figure 1a, 1b). In the in-vivo experiment, the initial recanalization time of PLT-r-SAK was significantly shorter than that of the low dose and high dose r-SAK, and the duration of the reperfusion time of PLT-r-SAK was prolonged compared to low dose and high dose r-SAK (Figure 1c). Another in-vitro experiment showed that the increased thrombolysis rate of PLT-r-SAK could be inhibited by platelet poor plasma (PPP) from aspirin- and ticagrelor-treated patients. Finally, both the in-vitro and in-vivo near-infrared fluorescence imaging showed significantly higher radiant efficiency in the PLT-r-SAK group as compared to the NS group (Figure 2). Conclusions Platelet membrane coating significantly improves the thrombolytic efficacy of r-SAK, which is related to the thrombus-targeting activity of the platelet membrane and can be inhibited by aspirin- and ticagrelor-treated plasma.Thrombolytic efficacy of PLT-r-SAKThrombus-targeting evidence of PLT-r-SAK

Some minutes matter more: Groin-to-recanalization is the main time-related predictor of outcome in acute ischemic stroke

Introduction Endovascular thrombectomy (EVT) is the standard of care for selected patients with acute ischemic stroke (AIS) and large vessel occlusion (LVO), associated with intravenous thrombolysis, when indicated. While many studies focused on pre-hospital and in-hospital pathways, only few analyzed the relationship between groin-to-recanalization (GTR) time and functional outcome. Aim To explore whether GTR time is an independent predictor of outcome in patients undergoing EVT. Methods All patients with anterior circulation stroke treated with EVT at a high-volume center from January 2021 to December 2023 were included. The cohort was divided into two groups according to GTR time shorter or longer than 30 min. Regression analysis assessed the association between GTR time and 3-month good outcome, defined as modified Rankin Scale 0–2. Results The study included 419 patients. The groups had similar baseline characteristics and similar onset to recanalization (OTR) time. Regression analysis showed shorter GTR time is an independent predictor of favorable outcome (OR 2.49 [95% CI 1.26–4.94]). Age, baseline NIHSS, ASPECT score and bridging IVT were also found to be independently associated with outcome. Discussion and conclusions Our study showed GTR time is an independent predictor of good outcome in patients undergoing EVT with similar OTR time, emphasizing procedural time as a key prognostic factor, even greater than other well-known pre-hospital and in-hospital time-dependent variables. These findings may raise the issue of developing alternative approaches or early “rescue” strategies for complicated procedures.

Age-related differences in diffusion-weighted imaging lesion volume and reversal in patients with successful recanalization after mechanical thrombectomy

BackgroundWith the advancement of mechanical thrombectomy (MT), post-treatment diffusion-weighted imaging (DWI) lesion reversal (DWIR) has been reported. This study aimed to compare the volumes of DWI lesions and the frequencies...

Assessment of Thrombectomy versus Combined Thrombolysis and Thrombectomy in Patients with Acute Ischemic Stroke and Medium Vessel Occlusion.

Background The combination of intravenous thrombolysis (IVT) with mechanical thrombectomy (MT) may have clinical benefits for patients with medium vessel occlusion. Purpose To examine whether MT combined with IVT is associated with different outcomes than MT alone in patients with acute ischemic stroke (AIS) and medium vessel occlusion. Materials and Methods This retrospective study included consecutive adult patients with AIS and medium vessel occlusion treated with MT or MT with IVT at 37 academic centers in North America, Asia, and Europe. Data were collected from September 2017 to July 2021. Propensity score matching was performed to reduce confounding. Univariable and multivariable logistic regression analyses were performed to test the association between the addition of IVT treatment and different functional and safety outcomes. Results After propensity score matching, 670 patients (median age, 75 years [IQR, 64-82 years]; 356 female) were included in the analysis; 335 underwent MT alone and 335 underwent MT with IVT. Median onset to puncture (350 vs 210 minutes, P < .001) and onset to recanalization (397 vs 273 minutes, P < .001) times were higher in the MT group than the MT with IVT group, respectively. In the univariable regression analysis, the addition of IVT was associated with higher odds of a modified Rankin Scale (mRS) score 0-2 (odds ratio [OR], 1.44; 95% CI: 1.06, 1.96; P = .019); however, this association was not observed in the multivariable analysis (OR, 1.37; 95% CI: 0.99, 1.89; P = .054). In the multivariable analysis, the addition of IVT also showed no evidence of an association with the odds of first-pass effect (OR, 1.27; 95% CI: 0.9, 1.79; P = .17), Thrombolysis in Cerebral Infarction grades 2b-3 (OR, 1.64; 95% CI: 0.99, 2.73; P = .055), mRS scores 0-1 (OR, 1.27; 95% CI: 0.91, 1.76; P = .16), mortality (OR, 0.78; 95% CI: 0.49, 1.24; P = .29), or intracranial hemorrhage (OR, 1.25; 95% CI: 0.88, 1.76; P = .21). Conclusion Adjunctive IVT may not provide benefit to MT in patients with AIS caused by distal and medium vessel occlusion. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Wojak in this issue.

Effects of emergent carotid stenting performed before or after mechanical thrombectomy in the endovascular management of patients with tandem lesion: a multicenter retrospective matched analysis.

Mechanical thrombectomy (MT) along with emergent carotid stenting (eCAS) have been suggested to have a greater benefit in patients with tandem lesion (TL), compared to other strategies of treatment. Nonetheless, there is no agreement on whether the intracranial occlusion should be treated before the cervical ICA lesion, or vice versa. In this retrospective multicenter study, we sought to compare clinical and procedural outcomes of the two different treatment approaches in patients with TL. The prospective databases of 17 comprehensive stroke centers were screened for consecutive patients with TL who received MT and eCAS. Patients were divided in two groups based on whether they received MT before eCAS (MT-first approach) or eCAS before MT (eCAS-first approach). Propensity score matching (PSM) was used to estimate the effect of the retrograde versus the anterograde approach on procedure-related and clinical outcome measures. These included the mTICI score 2b-3, other procedure-related parameters and adverse events after the endovascular procedure, and the ordinal distribution of the 90-day mRS scores. A total of 295 consecutive patients were initially enrolled. Among these, 208 (70%) received MT before eCAS. After PSM, 56 pairs of patients were available for analysis. In the matched population, the MT-first approach resulted in a higher rate of successful intracranial recanalization (91% versus 73% in the eCAS-first approach, p=0.025) and shorter groin-to-reperfusion time (72 ± 38 minutes versus 93 ± 50 minutes in the anterograde approach, p=0.017). Despite a higher rate of efficient recanalization in the MT-first group, we did not observe a significant difference concerning the ordinal distribution of the 90-day mRS scores. Rates of procedure-related adverse events and occurrence of both parenchymal hemorrhage type 1 and type 2 were comparable. Our study demonstrates that in patients with TL undergoing endovascular treatment, prioritizing the intracranial occlusion is associated with an increased rate of efficient MT and faster recanalization time. However, this strategy does not bring an advantage in long-term clinical outcome. Future controlled studies are needed to determine the optimal treatment technique. AIS = acute ischemic stroke; eCAS = emergent carotid stenting; ICA = internal carotid artery; GTR = groin-torecanalization; IVT = intravenous thrombolysis; LVO = large vessel occlusion; MCA, middle cerebral artery; MT = mechanical thrombectomy; PSM = propensity score matching; SMD = standardized mean difference; STROBE = STrengthening the Reporting of OBservational studies in Epidemiology; TL = tandem lesion.

Effect of Patient's Symptom Interpretation on In-Hospital Mortality in Acute Coronary Syndrome.

The association between symptom interpretation and prognosis has not been investigated well among patients with acute coronary syndrome (ACS). As such, the present study evaluated the effect of heart disease awareness among patients with ACS on in-hospital mortality. We performed a post hoc analysis of 1,979 consecutive patients with ASC with confirmed symptom interpretation on admission between 2014 and 2018, focusing on patient characteristics, recanalization time, and clinical outcomes. Upon admission, 1,264 patients interpreted their condition as cardiac disease, whereas 715 did not interpret their condition as cardiac disease. Although no significant difference was observed in door-to-balloon time between the 2 groups, onset-to-balloon time was significantly shorter among those who interpreted their condition as cardiac disease (254 vs. 345 min; P<0.001). Moreover, the hazard ratio (HR) for in-hospital mortality was significantly higher among those who did not interpret their condition as cardiac disease based on the Cox regression model adjusted for established risk factors (HR 1.73; 95% confidence interval 1.08-2.76; P=0.022). This study demonstrated that prehospital symptom interpretation was significantly associated with in-hospital clinical outcomes among patients with ACS. Moreover, the observed differences in clinical prognosis were not related to door-to-balloon time, but may be related to onset-to-balloon time.

Technical aspects and outcomes of endovascular treatment for vertebrobasilar tandem occlusions as compared to isolated basilar artery occlusion

Background: The optimal treatment approach for posterior circulation tandem occlusion remains unclear. This study aimed to assess the efficacy and safety of treatment strategies for vertebrobasilar tandem occlusions as compared to isolated basilar artery occlusions. This study investigates the challenges of managing these complex cerebrovascular conditions and explores the feasibility of optimizing treatment approaches to improve patient outcomes and safety. Methods: Fifty-nine patients with acute posterior large-vessel occlusion stroke who underwent mechanical thrombectomy between November 2016 and December 2022 were retrospectively analyzed. Patients were categorized as isolated or tandem basilar artery occlusion. The baseline patient characteristics, risk factors, time metrics, recanalization rates, and angiographic characteristics were compared between groups. The study analyzed various interventional strategies, including thrombectomy technique, additional angioplasty, the approach to lesion patterns (ipsilateral to steno-occlusive VA lesion: dirty road or contralateral: clean road), and the sequence of actions during the procedures. The outcome measures were a 90-day modified Rankin scale (mRS) of 4-6, post-thrombectomy recanalization defined as mTICI -2b, 90-day mortality. Results: Out of the 59 patients, 39 (66%) had isolated basilar occlusion(i-BAO), while 20 (33%) presented with tandem occlusions (t-BAO). Patients with i-BAO and t-BAO had mean ages of 59.08±12.53 and 56.30±12.94 years, respectively. Both groups had a median NIHSS score of 22 upon admission. t-BAO group had longer times from symptom onset to hospital admission and recanalization times compared to i-BAO. (median 270 min versus 60min, p=0.015; 384 min versus 240 min, p=0.03). Successful recanalization (modified thrombolysis in cerebral infarction score ≥2b) was obtained in 13 (76.4%) versus 35 (89.7%) patients with t-BAO versus i-BAO, respectively. Thrombectomy performed aspiration with a distal access catheter (CA) was more common in the isolated basilar occlusion group (73.7% vs. 43.8%). In contrast, stent retrievers (SR) were more common in the tandem group (37.5% vs. 18.4). Access was achieved in 17 patients with tandem occlusion. The clean road approach was used in 58.8 % of cases, and the dirty road in 41.2%. t-BAO procedures involved a higher number of intraprocedural passes (median 2.5 vs. 1.5, p=0.047). Third-month mortality rate was significantly higher in the t-BAO group (66.7% vs. 38.5%, p=0.047). Multivariate logistic regression identified a number of passes ≥3 as an independent risk factor for poor clinical outcome at three months (OR=14; 95% CI, 2.596-77.208). Conclusions: Endovascular intervention via mechanical thrombectomy has been demonstrated to be both safe and feasible as a treatment approach for patients presenting with tandem occlusions in the posterior circulation.

Effect of Endovascular Thrombectomy for Acute Ischemic Stroke on Cognitive Outcomes: A Secondary Analysis of the ESCAPE Trial.

The effect of endovascular therapy (EVT) for large vessel occlusion stroke on cognitive outcomes is not well understood. We evaluated the effect of EVT on cognitive function in the Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial. Patient data from the ESCAPE randomized trial were analyzed. Cognitive assessments completed at 90 days after stroke were the Montreal Cognitive Assessment (MoCA), the Sunnybrook Neglect Assessment Procedure (SNAP), the Boston Naming Test (BNT), Trail-making test A (Trails A), and Trail-making test B (Trails B). We used logistic regression to evaluate the association between EVT and favorable cognitive outcome on the 5 separate tests, adjusting for demographic and clinical factors. We used generalized estimating equations and ordinal regression to determine the odds of favorable outcome with EVT on global cognition incorporating the 5 tests. We added final infarct volume (FIV) to the models to assess the relationship of FIV with cognitive outcome. The ESCAPE trial included 315 patients, 165 randomized to EVT and 150 randomized to control. There was higher odds of favorable outcome with EVT for MoCA (adjusted odds ratio [aOR] 2.32, 95% CI 1.30-4.16), SNAP (aOR 3.85, 95% CI 2.00-7.45), BNT (aOR 2.33, 95% CI 1.30-4.17), trails A (aOR 3.50, 95% CI 1.93-6.36), and trails B (aOR 2.56, 95% CI 1.46-4.48). There was higher odds of favorable outcome with EVT on global binary (aOR 2.57, 95% CI 1.67-3.94) and ordinal analyses (aOR 2.83, 95% CI 1.68-4.76) of cognitive function. After adding FIV to the models, both FIV and EVT were significantly associated with cognitive outcome. There was a significant correlation between global cognitive performance and mRS at day 90 (r = -0.78, p < 0.001), with the largest reductions in favorable cognitive outcome from mRS score 4 to 5 and from mRS 2 to 3. In this secondary analysis of the ESCAPE trial, EVT was associated with favorable outcome on 5 separate cognitive tests and in global analyses of cognitive benefit. These results provide novel evidence for the effect of EVT on cognition and support the global benefit of treatment with EVT. This study provides Class II evidence that in patients with acute ischemic stroke due to intracranial internal carotid artery (ICA) or M1 segment MCA occlusion, including tandem extracranial ICA occlusions, EVT compared with best medical therapy increased odds of favorable cognitive outcome.

Utilizing a Guiding Catheter to Improve Endovascular Therapy Outcomes for Acute Vertebrobasilar Artery Occlusion in Patients with Tortuous Vessels.

Objective Stable and swift placement of a guiding catheter in endovascular therapies for acute vertebrobasilar artery occlusion is often difficult because of the tortuous bends of the vertebral or subclavian artery especially in older people. The use of a delivery assist guiding catheter (DAGC) shortens the time with stable support to deliver a therapeutic treatment catheter to the target lesions. Herein, we reported the clinical and radiographic outcomes in endovascular therapies utilizing the DAGC for acute vertebrobasilar artery occlusions in actual clinical settings. Materials and Methods Between January 2018 and December 2021, 33 consecutive patients (males, 20[60.6%]; median age, 78 years) using a DAGC for acute vertebrobasilar artery occlusion were analyzed retrospectively. Reperfusion was graded using postinterventional angiograms based on the "thrombolysis in cerebral infarction" (TICI) classification. Furthermore, the time from puncture to recanalization and the rate of effective recanalization achievement were investigated. Results Effective recanalization with TICI 2b or 3 was achieved in 28 (84.8%) patients, and the median time from puncture to recanalization was only 44 minutes, despite the high rate of older patients in our cohort. In contrast, asymptomatic intracranial hemorrhage as a complication was observed in only 3 (9.1%) patients. Conclusion The DAGC contributes to the shortening of recanalization time and improves the outcomes of endovascular therapies for acute vertebrobasilar artery occlusion.

Endovascular treatment of embolism-related acute basilar artery occlusion stroke: ADAPT versus stent retriever thrombectomy.

This study aimed to compare the efficacy and safety of a direct aspiration first-pass technique (ADAPT) and stent retriever thrombectomy (SRT) technique in embolism-related acute basilar artery occlusion (EMB-ABAO). We collected data from patients with EMB-ABAO in multiple stroke centers from January 2017 to February 2024. We defined two groups of enrolled patients, the ADAPT group and the SRT group. The primary outcome was the first attempt recanalization (FAR) rate. Secondary outcomes were the puncture to recanalization (PTR) time and the 90-day favorable functional outcome. The safety outcome was 90-day all-cause mortality rate. A total of 406 patients were screened for endovascular treatment (EVT) of ABAO ischemic stroke, and 108 patients were identified with EMB-ABAO stroke. Among these, 96 patients were included in the final analysis. Among them, 58 (60.42%) were in the ADAPT group, and 38 (39.58%) were in the SRT group. Compared with the SRT group, the ADAPT group achieved FAR more frequently (60.34% versus 39.47%; p = 0.045) and a higher 90-day favorable functional outcome rate (44.83% versus 36.84%; p = 0.438). The median PTR time of the ADAPT group was significantly shorter than that of the SRT group (42 versus 105 min; p < 0.001). In cases where EMB-ABAO is suspected, ADAPT was superior to SRT in terms of FAR rate and PTR time, but the 90-day mRS scores had no statistical significance. Given the reduced time to recanalization with ADAPT, an initial attempt at recanalization with ADAPT may be necessary before stent retriever. However, due to the study limitations, these findings should be interpreted as preliminary and require further study.

Comparison of Outcomes between Stent Retriever Combined with Contact Aspiration and Contact Aspiration Alone in Patients without Hyperdense Artery Sign/Susceptibility Vessel Sign

PurposeTo examine the relationship between hyperdense artery sign (HAS)/susceptibility vessel sign (SVS) and thrombus composition and evaluate the effect of HAS/SVS status on the association between first-line thrombectomy techniques and outcomes in patients with acute anterior circulation large vessel occlusion (LVO). Materials and MethodsFrom January 2018 to June 2021, 103 consecutive patients with acute anterior circulation LVO (75 [63.1%] men; median age, 66 years) who underwent thrombectomy and for whom the removed clot was available for histological analyses were retrospectively reviewed. The presence of HAS and SVS was assessed on unenhanced computed tomography (CT) and susceptibility-weighted imaging, respectively. Association of first-line thrombectomy techniques (stent retriever [SR] combined with contact aspiration [CA] vs CA alone) with outcomes was assessed according to HAS/SVS status. ResultsAmong the included patients, 55 (53.4%) were HAS/SVS-negative, and 69 (67.0%) underwent first-line SR + CA. Higher relative densities of fibrin/platelets (0.56 vs 0.51; P < .001) and lower relative densities of erythrocytes (0.32 vs 0.42; P < .001) were observed in HAS/SVS-negative patients compared with HAS/SVS-positive patients. First-line SR + CA was associated with reduced odds of distal embolization (adjusted odds ratio, 0.18; 95% CI, 0.04–0.83; P = .027) and a more favorable 90-day functional outcome (adjusted odds ratio, 5.29; 95% CI, 1.06–26.34; P = .042) in HAS/SVS-negative patients and a longer recanalization time (53 vs 25 minutes; P = .025) and higher risk of subarachnoid hemorrhage (24.2% vs 0%; P = .044) in HAS/SVS-positive patients. ConclusionsAbsence of HAS/SVS may indicate a higher density of fibrin/platelets in the thrombus, and first-line SR + CA yielded superior functional outcomes than CA alone in patients with acute LVO without HAS/SVS.

Optimizing catheter centering enhances mechanical thrombectomy success: Performance difference in cases using novel macrowires versus traditional microwires.

The aim of this study is to determine how guidewire selection impacts procedure time and success and analyze if the trend toward the adoption of larger diameter guidewires provides a quantifiable advantage over traditional 0.014″ guidewires. A review of 494 consecutively performed acute ischemic stroke cases performed between 2018 and 2022 were reviewed and grouped into cases using a single 0.014″ outer diameter (OD) guidewire (195 cases) and cases using a single 0.018″ or 0.024″ OD guidewire (128 cases). These groups were compared for differences in average time to recanalization, average number of passes to achieve recanalization, and first pass success. Cases were compared overall, and further analyzed by region of occlusion to look at specific guidewire related differences for cases with M1, M2, and ICA occlusions. Procedures using a larger OD guidewire have an average 5 min and 30 s reduction in time from puncture to recanalization (p = 0.0201). ICA occlusion cases using a larger macrowire show a 20 min reduction in recanalization time (p = 0.0005), a reduction in average number of passes from 2.6 to 1.7 (p = 0.0058), and an increase in first pass success from 18.8% to 58.3% when compared to traditional guidewires. Large 0.018″ or 0.024″ OD guidewires better fill the lumen of the catheter and help to center the thrombectomy system in the vessel and navigate to the clot face. This leads to a reduction in procedure time and number of passes, and an increase in first pass success, especially when treating occlusions in the ICA.

Platelet Membrane-Coated r-SAK Improves Thrombolytic Efficacy by Targeting Thrombus.

Thrombolytic therapy is one of the most effective treatments for thrombus dissolution and recanalization of blocked vessels in thrombotic diseases. However, the application of the thrombolytic strategy has been limited due to unsatisfactory thrombolytic efficacy, relatively higher bleeding complications, and consequently restricted indications. Recombinant staphylokinase (r-SAK) is a third-generation thrombolytic agent produced by genetic engineering technology, which exhibits a better thrombolytic efficacy than urokinase and recombinant streptokinase. Inspired by the natural affinity of platelets in hemostasis and pathological thrombosis, we developed a platelet membrane (PM)-coated r-SAK (PM-r-SAK). Results from animal experiments and human in vitro studies showed that the PM-r-SAK had a thrombolytic efficacy equal to or better than its 4-fold dose of r-SAK. In a totally occluded rabbit femoral artery thrombosis model, the PM-r-SAK significantly shortened the initial recanalization time compared to the same dose and 4-fold dose of r-SAK. Regarding the recanalized vessels, the PM-r-SAK prolonged the time of reperfusion compared to the same dose and 4-fold dose of r-SAK, though the differences were not significant. An in vitro thrombolytic experiment demonstrated that the thrombolytic efficacy of PM-r-SAK could be inhibited by platelet-poor plasma from patients taking aspirin and ticagrelor. PM coating significantly improves the thrombolytic efficacy of r-SAK, which is related to the thrombus-targeting activity of the PM-r-SAK and can be inhibited by aspirin- and ticagrelor-treated plasma.

A novel nomogram to predict futile recanalization in patients with acute ischemic stroke undergoing mechanical thrombectomy.

Futile recanalization (FR) is defined as patients with acute ischemic stroke (AIS) due to large vessel occlusion who still exhibits functional dependence although undergoing successful mechanical thrombectomy (MT). We aimed to develop and validate a simple nomogram for predicting the probability of FR after MT treatment in AIS patients. Clinical data of AIS patients in the Jrecan clinical trial in China from March 2018 to June 2019 were collected as the derivation set (n = 162). Meanwhile, clinical data of AIS patients who underwent MT in Baotou Central Hospital and Ningbo No.2 Hospital from 2019 to 2021 were collected as the validation set (n = 170). Multivariate logistic regression analysis was performed for all variables that had p < 0.2 in the univariate analysis in the derivation set. The independent risk factors of FR were further screened out and a nomogram was constructed. The performance of the nomogram was analyzed in the derivation and validation set using C-index, calibration plots, and decision curves. No significant difference in FR rate was detected between the derivation set and the validation set [88/162 (54.32%) and 82/170 (48.23%), p = 0.267]. Multivariate logistic regression analysis showed that age ≥ 65 years old (OR = 2.096, 95%CI 1.024-4.289, p = 0.043), systolic blood pressure (SBP) ≥ 180 mmHg (OR = 5.624, 95%CI 1.141-27.717, p = 0.034), onset to recanalization time (OTR) ≥ 453 min (OR = 2.759, 95%CI 1.323-5.754, p = 0.007), 24 h intracerebral hemorrhage (ICH; OR = 4.029, 95%CI 1.844 ~ 8.803, p < 0.001) were independent risk factors for FR. The C-index of the nomogram of the derivation set and the verification set were 0.739 (95%CI 0.662~0.816) and 0.703 (95%CI 0.621~0.785), respectively. The nomogram composed of age, SBP, OTR, and 24 h ICH can effectively predict the probability of FR after MT in AIS patients.

Anesthetic management for large vessel occlusion acute ischemic stroke with tandem lesions

BackgroundEndovascular therapy (EVT) stands as an established and effective intervention for acute ischemic stroke in patients harboring tandem lesions (TLs). However, the optimal anesthetic strategy for EVT in TL patients...

In silico study of combination thrombolytic therapy with alteplase and mutant pro-urokinase for fibrinolysis in ischemic stroke

The synergistic advantage of combining tissue plasminogen activator (tPA) with pro-urokinase (proUK) for thrombolysis has been demonstrated in several in vitro experiments, and a single site proUK mutant (m-proUK) has been developed for better stability in plasma. Based on these studies, combination thrombolytic therapy with intravenous tPA and m-proUK has been suggested as a promising treatment for patients with ischemic stroke. This paper evaluates the efficacy and safety of the dual therapy by computational simulations of pharmacokinetics and pharmacodynamics coupled with a local fibrinolysis model. Seven dose regimens are simulated and compared with the standard intravenous tPA monotherapy. Our simulation results provide more insights into the complementary reaction mechanisms of tPA and m-proUK during clot lysis and demonstrate that the dual therapy can achieve a similar recanalization time (about 50 min) to tPA monotherapy, while keeping the circulating fibrinogen level within a normal range. Specifically, our results show that for all dual therapies with a 5 mg tPA bolus, the plasma concentration of fibrinogen remains stable at around 7.5 μM after a slow depletion over 50 min, whereas a rapid depletion of circulating fibrinogen (to 5 μM) is observed with the standard tPA therapy, indicating the potential advantage of dual therapy in reducing the risk of intracranial hemorrhage. Through simulations of varying dose combinations, it has been found that increasing tPA bolus can significantly affect fibrinogen level but only moderately improves recanalization time. Conversely, m-proUK doses and infusion duration exhibit a mild impact on fibrinogen level but significantly affect recanalization time. Therefore, future optimization of dose regimen should focus on limiting the tPA bolus while adjusting m-proUK dosage and infusion rate. Such adjustments could potentially maximize the therapeutic advantages of this combination therapy for ischemic stroke treatment.

Abstract TP209: Prevalence of Spontaneous Recanalization of Internal Carotid Occlusion: A Systematic Scoping Review

Introduction: Spontaneous recanalization of occluded internal carotid arteries (ICAs) is thought to be an uncommon etiology of recurrent ischemic stroke. However, there is a growing number of reports describing this phenomenon, suggesting that follow-up investigations and/or intervention may be warranted. Our objective was to perform a scoping review of the literature to estimate the prevalence of spontaneous ICA recanalization and the timing of recanalization, and to describe imaging modalities used in follow-up as well as any post-recanalization interventions. Methods: MEDLINE, Embase, Cochrane Central Register of Controlled Trials and Web of Science were searched from inception to June 2022 for studies that included adults with spontaneous recanalization or transient occlusion of the internal carotid artery. Two investigators independently screened the studies and extracted data around recanalization prevalence, timepoints, imaging, and treatment. These results were described qualitatively, and descriptive statistics were calculated where appropriate. Results: Among the 2384 studies retrieved, 51 met inclusion criteria, of which 34 were case studies and 17 were cohort studies, with a total of 816 patients. Prevalence of recanalization was reported in 20 studies (3 case studies, 17 cohort studies) at a median of 40.0% (IQR 22.5 - 40.0%) in case studies, and 21.2% (IQR 9.2 - 37.5%) in cohort studies. Forty-one studies reported a time frame for when recanalization was identified, with 53.7% individual cases in case studies and 33.3% amongst cohort studies identified within the first 3 months after occlusion. When reported, antiplatelet treatment was the most common medical treatment pre- and post-recanalization with 189 and 36 individuals, respectively. Finally, doppler imaging was used in 70.6% of studies to identify recanalization, with angiography as the next most common modality at 54.9%. Twenty studies reported an endovascular intervention. Conclusions: Spontaneous recanalization occurs more commonly than previously thought. Currently there is no consensus on what intervention is needed (if any), or when this intervention would occur. More data is needed to confirm this data and determine the best time frame to re-image.

Abstract WP182: Effect of Prior Anticoagulation With Non-Vitamin K Oral Anticoagulants in Patients With Atrial Fibrillation on Functional and Procedural Outcomes in Patients Undergoing Thrombectomy

Background: Atrial fibrillation (AF) has been shown to be associated with better procedural outcomes in patients with anterior circulation large vessel occlusion (aLVO) undergoing endovascular therapy (EVT). However, data surrounding the impact of pre-treatment with NOACs on procedural outcomes among patients with AF undergoing EVT for aLVO remains limited. Methods: We conducted a retrospective analysis of a prospectively maintained institutional database of EVT cases on all patients with a diagnosis of AF between Jan 2021 and Mar 2023, grouped by anticoagulation (AC) status (AC vs no AC). In the anticoagulated group, only patients on NOACs were included. Outcomes compared between groups were 90-day mRS, successful reperfusion (Thrombolysis In Cerebral Infarction (TICI) 2b-3), first-pass effect (FPE), time from skin puncture to recanalization, symptomatic intracerebral hemorrhage (sICH), and 90-day mortality. Results: Of 197 AF patients included, 97 (49.2%) had a history of being on NOAC at the time of stroke. Forty-four percent of the no AC group received intravenous thrombolysis (IVT). In the NOAC group, 59.5% of patients achieved 90-day mRS of 0-2 vs 49.3% in the no AC group (aOR=1.32, p=0.57). The rate of successful reperfusion in the NOAC group was 98.7% vs 93% in no AC group, (aOR 0.48, p=0.24). No difference was observed with regards to FPE and skin puncture to recanalization time. There was a non-significant trend of higher mortality in the no AC group (23.9% versus 12.2% in NOAC group), despite similar sICH rates (5.0% in no AC and 6.2% in NOAC group, aOR 1.08, p=0.91). Subgroup analysis of patients with a single, non-tandem occlusion of ICA or M1 analyzed by NOAC status yielded similar findings. All outcomes were adjusted for age, gender, baseline NIHSS, and IVT status. Conclusion: Among patients with AF undergoing EVT for LVO, our study did not find an association of prior anticoagulation with NOACs on procedural outcomes, although there was a trend towards better functional outcomes and numerically higher successful reperfusion rate among patients pretreated with NOACs. Further research is needed to study the impact of NOACs on procedural outcomes among patients undergoing EVT.

Abstract WP125: The Presence of a Ghost Infarct Core is Associated With Fast Core Growth in Acute Ischemic Stroke

Introduction: The overestimation of ischemic core volume by computed tomography perfusion (CTP) is a critical concern in the selection of candidates for reperfusion therapy. This phenomenon is termed a ghost infarct core (GIC). Core growth rate has emerged as an indicator of ischemic severity. The aim of the present study was to elucidate the association between the presence of a GIC and the core growth rate. Methods: Consecutive patients with acute ischemic stroke due to large vessel occlusion who underwent mechanical thrombectomy in our institute from March 2017 to July 2022 were enrolled. The initial ischemic core was measured by pretreatment CTP, and the final infarct volume (FIV) was measured by diffusion-weighted imaging. A GIC was defined by initial ischemic core volume minus FIV &gt;10 mL. The core growth rate was calculated by dividing the initial ischemic core volume by time from stroke onset to CTP acquisition. Univariable analysis and a multivariable logistic regression model were used to evaluate the association between GIC-positive and the core growth rate; complete recanalization, onset to imaging time, and imaging to recanalization time were included as covariates. Results: Ninety-one patients were included in the study. Of these, 21 patients (23.1%) were GIC-positive. The GIC-positive group had higher core growth rate (14.2 [2.6-46.7] vs 4.8 [1.6-17.1] mL/h, p=0.021) and complete recanalization (n=15 (71.4%) vs 29 (41.4%), p=0.016) compared to the GIC-negative group. On receiver operating characteristic curve analysis, the optimal cutoff point of the core growth rate to predict GIC-positive was 22 mL/h (sensitivity, 0.48; specificity, 0.85; area under the curve, 0.67). Multivariable logistic regression analysis showed that core growth rate ≥22 mL/h (OR 6.44, 95% CI [1.59-26.10], p=0.006) and complete recanalization (OR 3.72, 95% CI [1.14-12.08], p=0.022) were independent predictors of GIC-positive. Conclusions: A GIC was associated with fast core growth in acute ischemic stroke. Overestimation of the initial ischemic core may be determined by core growth speed, not a clock time.

A nomogram predicting the relationship between recanalization time and successful endovascular recanalization of non-acute internal carotid artery occlusion in a Chinese population.

Different recanalization times for endovascular interventions may affect the success of non-acute internal carotid artery occlusion procedures. Nomograms can provide personalized and more accurate risk estimates based on predictive values. Therefore, we developed a nomogram to predict the probability of success of endovascular recanalization procedures for non-acute internal carotid artery occlusion. We performed a single-center retrospective analysis of data collected from patients who underwent endovascular treatment for non-acute internal carotid artery occlusion between January 2015 and December 2022. Multifactorial logistic regression analyses were performed to identify independent predictors affecting the success rate of non-acute internal carotid artery occlusion procedures and to create nomograms. The model was differentiated and calibrated using the area under the ROC curve (AUC-ROC) and calibration plots. Internal validation of the model was performed by using resampling (1000 replications). In total, 46 patients were identified and a total of 39 patients met the study criteria. Predictors in the nomogram included vascular occlusion proximal morphology, reversed flow of the ophthalmic artery, and recanalization time. The model showed good resolution with an ROC area of 0.917 (95% CI: 0.814-0.967). The nomogram can be used to personalize, visualize, and accurately predict the surgical success of endovascular treatment of non-acute internal carotid artery occlusion.