Effect of Hemoglobin and Blood Glucose Levels on CT Perfusion Ischemic Core Estimation: A Post Hoc Analysis of the ESCAPE-NA1 Trial.

BACKGROUND AND OBJECTIVES: CT perfusion (CTP) maps can estimate the ischemic core in acute ischemic stroke based on distinctive cerebral blood flow thresholds. However, metabolic factors beyond perfusion influence the tissue tolerance to ischemia and the infarct growth rate. Underestimating the ischemic core volume (ICV) might result in overestimating the salvageable cerebral tissue and, consequently, overestimating the potential clinical benefits of reperfusion therapies. We aim to evaluate whether baseline hemoglobin and blood glucose levels influence the accuracy of baseline CTP ICV estimations. METHODS: Large vessel occlusion stroke patients investigated with baseline CTP undergoing thrombectomy with near-complete reperfusion and without parenchymal hemorrhage from the ESCAPE-NA1 trial were included. Patients were subdivided into anemic (hemoglobin <130 g/L for men and <120 g/L for women) and nonanemic groups, and hyperglycemic (blood glucose level >7 mmol/L) and normoglycemic groups. Ischemic core underestimated volume (ICuV) was calculated: final infarct volume minus CTP-based ICV. The primary outcome was the presence of "perfusion scotoma" defined as ICuV ≥10 mL. Presence of "perfusion scotoma" and median ICuV were compared between anemic vs nonanemic and hyperglycemic vs normoglycemic patients using nonparametric tests and multivariable binary logistic regression with adjustment for baseline variables. RESULTS: One hundred sixty-two of 1,105 (15%) patients were included (median age 70.5 [interquartile range (IQR) 61-80.4], 50.6% women). The median ICuV was 7.26 mL (IQR 0-25.63). Seventy-eight (48%) patients demonstrated perfusion scotoma. Forty-two (25.7%) patients were anemic, and 65 (40.1%) were hyperglycemic. In univariable analysis, the hyperglycemic group had a higher prevalence of perfusion scotoma (65% [n = 40] vs 39% [n = 38], p = 0.006) and larger ICuV (17.79 mL [IQR 1.57-42.75] vs 6 mL [-0.31 to 12.51], p = 0.003) compared to normoglycemic patients. No significant ICuV differences between patients with and without anemia were seen. Multivariable regression analysis revealed an association between perfusion scotoma and hyperglycemia, adjusted odds ratio (OR) 2.48 (95% CI 1.25-4.92), and between perfusion scotoma and blood glucose levels, adjusted OR 1.19 (95% CI 1.03-1.39) per 1 mmol/L increase. DISCUSSION: In our study, CTP-based ischemic core underestimation was common and associated with higher baseline blood glucose levels. Individual metabolic factors beyond perfusion that critically influence the infarct growth rate should be considered when interpreting baseline CTP estimations of ischemic core.

Gestodene, a novel positive allosteric modulator of PAR1, enhances PAR1-mediated human platelet aggregation.

Background: Protease-activated receptor 1 (PAR1) is expressed in human platelets and can be activated by low concentrations of thrombin. Vorapaxar, a selective antagonist of PAR1, inhibits thrombin-induced calcium mobilization in human platelet, which is associated with an increased risk of bleeding. Conversely, the administration of a positive allosteric modulator (PAM) of PAR1 may pose a substantial risk of thrombosis due to inducing excessive platelet activation. In this study, we discovered a novel PAM of PAR1 and investigated the effect of enhanced PAR1 activation by PAM of PAR1 on platelet activation. Methods: To find PAMs of PAR1, a cell-based screen was performed in HT29 cells, and finally, gestodene, an oral contraceptive drug (OC), was identified as a novel PAM of PAR1. The mechanism of action of gestodene and its effects on platelet activation were investigated in human megakaryocytic leukemia cell line MEG-01 cells and human platelet. Results: Gestodene enhanced both thrombin- and PAR1-activating peptide (AP)-induced intracellular calcium levels in a dose-dependent manner without altering PAR2 and PAR4 activity. Gestodene significantly increased PAR1-AP-induced internalization of PAR1 and phosphorylation of ERK1/2, and the enhancing effects were significantly blocked by vorapaxar. Furthermore, gestodene potently increased PAR1-AP induced morphological changes in MEG-01 cells. Remarkably, in human blood, gestodene exerted a robust augmentation of PAR1-AP-induced platelet aggregation, and vorapaxar effectively attenuated the gestodene-induced enhancement of platelet aggregation mediated by PAR1. Conclusion: Gestodene is a selective PAM of PAR1 and suggest one possible mechanism for the increased risk of venous thromboembolism associated with OCs containing gestodene.

Cancer-Associated Stroke: Thrombosis Mechanism, Diagnosis, Outcome, and Therapeutic Strategies.

Cancer can induce hypercoagulability, which may lead to stroke. This occurs when tumor cells activate platelets as part of their growth and metastasis. Tumor cells activate platelets by generating thrombin and expressing tissue factor, resulting in tumor cell-induced platelet aggregation. Histopathological studies of thrombi obtained during endovascular thrombectomy in patients with acute stroke and active cancer have shown a high proportion of platelets and thrombin. This underscores the crucial roles of platelets and thrombin in cancer-associated thrombosis. Cancer-associated stroke typically occurs in patients with active cancer and is characterized by distinctive features. These features include multiple infarctions across multiple vascular territories, markedly elevated blood D-dimer levels, and metastasis. The presence of cardiac vegetations on echocardiography is a robust indicator of cancer-associated stroke. Suspicion of cancer-associated stroke during endovascular thrombectomy arises when white thrombi are detected, particularly in patients with active cancer. Cancer-associated stroke is almost certain when histopathological examination of thrombi shows a very high platelet and a very low erythrocyte composition. Patients with cancer-associated stroke have high risks of mortality and recurrent stroke. However, limited data are available on the optimal treatment regimen for stroke prevention in these patients. Thrombosis mechanism in cancer is well understood, and distinct therapeutic targets involving thrombin and platelets have been identified. Therefore, direct thrombin inhibitors and/or antiplatelet agents may effectively prevent stroke recurrence. Additionally, this strategy has potential benefits in cancer treatment as accumulating evidence suggests that aspirin use reduces cancer progression, metastasis, and cancer-related mortality. However, clinical trials are necessary to assess the efficacy of this strategy involving the use of direct thrombin inhibitors and/or antiplatelet therapies.

Prognosis of ischemic stroke patients with both aortic atheroma and cardioembolic sources.

This study aimed to investigate the relationship between complex aortic plaque (CAP) and short-term as well as long-term outcomes following cardioembolic stroke. CAP is a known risk factor for occurrence and recurrence of ischemic stroke. However, the association of CAP on cardioembolic stroke remains unclear. This was retrospective study using prospective cohort of consecutive patients with cardioembolic stroke who underwent transesophageal echocardiography. The functional outcome was evaluated using the modified Rankin Scale score at 3 months, and long-term outcomes were assessed by recurrence of ischemic stroke and occurrence of major adverse cardiovascular events (MACE). Among 759 patients with cardioembolic stroke, 91 (12.0%) had CAP. Early ischemic stroke recurrence within 3 months was associated with CAP (p = 0.025), whereas CAP was not associated with functional outcome at 3 months (odd ratio 1.01, 95% confidence interval [CI] 0.57-1.84, p = 0.973). During a median follow-up of 3.02 years, CAP was significantly associated with ischemic stroke recurrence (hazard ratio = 2.68, 95% CI 1.48-4.88, p = 0.001) and MACE occurrence (hazard ratio = 1.61, 95% CI 1.03-2.51, p = 0.039). In conclusion, CAP was associated with early ischemic stroke recurrence and poor long-term outcomes in patients with cardioembolic stroke. It might be helpful to consider transesophageal echocardiography for patients with cardioembolic stroke to identify CAP.

Impact of intensive blood pressure lowering after multiple-attempt endovascular thrombectomy: A secondary analysis of the OPTIMAL-BP trial.

BACKGROUND: Multiple attempts of thrombectomy have been linked to a higher risk of intracerebral hemorrhage and worsened functional outcomes, potentially influenced by blood pressure (BP) management strategies. Nonetheless, the impact of intensive BP management following successful recanalization through multiple attempts remains uncertain. AIMS: This study aimed to investigate whether conventional and intensive BP managements differentially affect outcomes according to multiple-attempt recanalization (MAR) and first-attempt recanalization (FAR) groups. METHODS: In this secondary analysis of the OPTIMAL-BP trial, which was a comparison of intensive (systolic BP target: <140 mm Hg) and conventional (systolic BP target = 140-180 mm Hg) BP managements during the 24 h after successful recanalization, we included intention-to-treat population of the trial. Patients were divided into the MAR and the FAR groups. We examined a potential interaction between the number of thrombectomy attempts (MAR and FAR groups) and the effect of BP managements on clinical and safety outcomes. The primary outcome was functional independence at 3 months. Safety outcomes were symptomatic intracerebral hemorrhage within 36 h and mortality within 3 months. RESULTS: Of the 305 patients (median = 75 years), 102 (33.4%) were in the MAR group and 203 (66.6%) were in the FAR group. The intensive BP management was significantly associated with a lower rate of functional independence in the MAR group (intensive, 32.7% vs conventional, 54.9%, adjusted odds ratio (OR) = 0.33, 95% confidence interval (CI) = 0.12-0.90, p = 0.03). In the FAR group, the proportion of patients with functional independence was not significantly different between the BP managements (intensive, 42.5% vs conventional, 54.2%, adjusted OR = 0.73, 95% CI = 0.38-1.40). Incidences of symptomatic intracerebral hemorrhage and mortality rates were not significantly different according to the BP managements in both MAR and FAR groups. CONCLUSIONS: Among stroke patients who received multiple attempts of thrombectomy, intensive BP management for 24 h resulted in a reduced chance of functional independence at 3 months and did not reduce symptomatic intracerebral hemorrhage following successful reperfusion.

Functional Outcomes Associated With Blood Pressure Decrease After Endovascular Thrombectomy.

Importance: The associations between blood pressure (BP) decreases induced by medication and functional outcomes in patients with successful endovascular thrombectomy remain uncertain. Objective: To evaluate whether BP reductions induced by intravenous BP medications are associated with poor functional outcomes at 3 months. Design, Setting, and Participants: This cohort study was a post hoc analysis of the Outcome in Patients Treated With Intra-Arterial Thrombectomy-Optimal Blood Pressure Control trial, a comparison of intensive and conventional BP management during the 24 hours after successful recanalization from June 18, 2020, to November 28, 2022. This study included 302 patients who underwent endovascular thrombectomy, achieved successful recanalization, and exhibited elevated BP within 2 hours of successful recanalization at 19 stroke centers in South Korea. Exposure: A BP decrease was defined as at least 1 event of systolic BP less than 100 mm Hg. Patients were divided into medication-induced BP decrease (MIBD), spontaneous BP decrease (SpBD), and no BP decrease (NoBD) groups. Main Outcomes and Measures: The primary outcome was a modified Rankin scale score of 0 to 2 at 3 months, indicating functional independence. Primary safety outcomes were symptomatic intracerebral hemorrhage within 36 hours and mortality due to index stroke within 3 months. Results: Of the 302 patients (median [IQR] age, 75 [66-82] years; 180 [59.6%] men), 47 (15.6%)were in the MIBD group, 39 (12.9%) were in the SpBD group, and 216 (71.5%) were in the NoBD group. After adjustment for confounders, the MIBD group exhibited a significantly smaller proportion of patients with functional independence at 3 months compared with the NoBD group (adjusted odds ratio [AOR], 0.45; 95% CI, 0.20-0.98). There was no significant difference in functional independence between the SpBD and NoBD groups (AOR, 1.41; 95% CI, 0.58-3.49). Compared with the NoBD group, the MIBD group demonstrated higher odds of mortality within 3 months (AOR, 5.15; 95% CI, 1.42-19.4). The incidence of symptomatic intracerebral hemorrhage was not significantly different among the groups (MIBD vs NoBD: AOR, 1.89; 95% CI, 0.54-5.88; SpBD vs NoBD: AOR, 2.75; 95% CI, 0.76-9.46). Conclusions and Relevance: In this cohort study of patients with successful endovascular thrombectomy after stroke, MIBD within 24 hours after successful recanalization was associated with poor outcomes at 3 months. These findings suggested lowering systolic BP to below 100 mm Hg using BP medication might be harmful.

Statin Therapy for Secondary Prevention in Ischemic Stroke Patients With Cerebral Microbleeds.

BACKGROUND AND OBJECTIVES: The association between statin use and the risk of intracranial hemorrhage (ICrH) following ischemic stroke (IS) or transient ischemic attack (TIA) in patients with cerebral microbleeds (CMBs) remains uncertain. This study investigated the risk of recurrent IS and ICrH in patients receiving statins based on the presence of CMBs. METHODS: We conducted a pooled analysis of individual patient data from the Microbleeds International Collaborative Network, comprising 32 hospital-based prospective studies fulfilling the following criteria: adult patients with IS or TIA, availability of appropriate baseline MRI for CMB quantification and distribution, registration of statin use after the index stroke, and collection of stroke event data during a follow-up period of ≥3 months. The primary endpoint was the occurrence of recurrent symptomatic stroke (IS or ICrH), while secondary endpoints included IS alone or ICrH alone. We calculated incidence rates and performed Cox regression analyses adjusting for age, sex, hypertension, atrial fibrillation, previous stroke, and use of antiplatelet or anticoagulant drugs to explore the association between statin use and stroke events during follow-up in patients with CMBs. RESULTS: In total, 16,373 patients were included (mean age 70.5 ± 12.8 years; 42.5% female). Among them, 10,812 received statins at discharge, and 4,668 had 1 or more CMBs. The median follow-up duration was 1.34 years (interquartile range: 0.32-2.44). In patients with CMBs, statin users were compared with nonusers. Compared with nonusers, statin therapy was associated with a reduced risk of any stroke (incidence rate [IR] 53 vs 79 per 1,000 patient-years, adjusted hazard ratio [aHR] 0.68 [95% CI 0.56-0.84]), a reduced risk of IS (IR 39 vs 65 per 1,000 patient-years, aHR 0.65 [95% CI 0.51-0.82]), and no association with the risk of ICrH (IR 11 vs 16 per 1,000 patient-years, aHR 0.73 [95% CI 0.46-1.15]). The results in aHR remained consistent when considering anatomical distribution and high burden (≥5) of CMBs. DISCUSSION: These observational data suggest that secondary stroke prevention with statins in patients with IS or TIA and CMBs is associated with a lower risk of any stroke or IS without an increased risk of ICrH. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with IS or TIA and CMBs, statins lower the risk of any stroke or IS without increasing the risk of ICrH.

Effectiveness of endovascular treatment for in-hospital stroke vs. community-onset stroke: a propensity score-matched analysis.

BACKGROUND: The effectiveness of endovascular treatment for in-hospital stroke remains debatable. We aimed to compare the outcomes between patients with in-hospital stroke and community-onset stroke who received endovascular treatment. METHODS: This prospective registry-based cohort study included consecutive patients who underwent endovascular treatment from January 2013 to December 2022 and were registered in the Selection Criteria in Endovascular Thrombectomy and Thrombolytic Therapy study and Yonsei Stroke Cohort. Functional outcomes at day 90, radiological outcomes, and safety outcomes were compared between the in-hospital and community-onset groups using logistic regression and propensity score-matched analysis. RESULTS: Of 1,219 patients who underwent endovascular treatment, 117 (9.6%) had in-hospital stroke. Patients with in-hospital onset were more likely to have a pre-stroke disability and active cancer than those with community-onset. The interval from the last known well to puncture was shorter in the in-hospital group than in the community-onset group (155 vs. 355 min, p<0.001). No significant differences in successful recanalization or safety outcomes were observed between the groups; however, the in-hospital group exhibited worse functional outcomes and higher mortality at day 90 than the community-onset group (all p<0.05). After propensity score matching including baseline characteristics, functional outcomes after endovascular treatment did not differ between the groups (OR: 1.19, 95% CI 0.78-1.83, p=0.4). Safety outcomes did not significantly differ between the groups. CONCLUSION: Endovascular treatment is a safe and effective treatment for eligible patients with in-hospital stroke. Our results will help physicians in making decisions when planning treatment and counseling caregivers or patients.

Initial stroke severity and discharge outcome in patients with muscle mass deficit.

This study aimed to investigate the association between muscle mass deficit and the initial severity of ischemic stroke. The impact of muscle mass deficit on the discharge outcome was also evaluated. This retrospective study included 660 patients with acute ischemic stroke who underwent bioelectrical impedance analyses. We compared the National Institute of Health Stroke Scale (NIHSS) score, occurrence of moderate stroke (NIHSSS ≥ 5) at admission, and unfavorable functional outcome (modified Rankin Scale score ≥ 2) at discharge between patients with and without muscle mass deficit using Poisson and logistic regression analyses. The mean age of the study patients was 65.6 ± 13.0, and 63.3% were males. Muscle mass deficit was present in 24.4% of patients. Muscle mass deficit was significantly and independently associated with NIHSS score or moderate stroke (all p < 0.05). This association was noted regardless of patient characteristics. Among the respective NIHSS items, muscle mass deficit was significantly associated with facial palsy, motor function of the arm or leg, limb ataxia, and dysarthria. Muscle mass deficit also led to unfavorable functional outcome, which was mediated by the initial NIHSS score. In conclusion, muscle mass deficit is associated with higher NIHSS score and unfavorable functional outcome in patients with acute ischemic stroke.

Clinical Associations and Prognostic Value of MRI-Visible Perivascular Spaces in Patients With Ischemic Stroke or TIA: A Pooled Analysis

BACKGROUND AND OBJECTIVES: Visible perivascular spaces are an MRI marker of cerebral small vessel disease and might predict future stroke. However, results from existing studies vary. We aimed to clarify this through a large collaborative multicenter analysis. METHODS: We pooled individual patient data from a consortium of prospective cohort studies. Participants had recent ischemic stroke or transient ischemic attack (TIA), underwent baseline MRI, and were followed up for ischemic stroke and symptomatic intracranial hemorrhage (ICH). Perivascular spaces in the basal ganglia (BGPVS) and perivascular spaces in the centrum semiovale (CSOPVS) were rated locally using a validated visual scale. We investigated clinical and radiologic associations cross-sectionally using multinomial logistic regression and prospective associations with ischemic stroke and ICH using Cox regression. RESULTS: We included 7,778 participants (mean age 70.6 years; 42.7% female) from 16 studies, followed up for a median of 1.44 years. Eighty ICH and 424 ischemic strokes occurred. BGPVS were associated with increasing age, hypertension, previous ischemic stroke, previous ICH, lacunes, cerebral microbleeds, and white matter hyperintensities. CSOPVS showed consistently weaker associations. Prospectively, after adjusting for potential confounders including cerebral microbleeds, increasing BGPVS burden was independently associated with future ischemic stroke (versus 0-10 BGPVS, 11-20 BGPVS: HR 1.19, 95% CI 0.93-1.53; 21+ BGPVS: HR 1.50, 95% CI 1.10-2.06; p = 0.040). Higher BGPVS burden was associated with increased ICH risk in univariable analysis, but not in adjusted analyses. CSOPVS were not significantly associated with either outcome. DISCUSSION: In patients with ischemic stroke or TIA, increasing BGPVS burden is associated with more severe cerebral small vessel disease and higher ischemic stroke risk. Neither BGPVS nor CSOPVS were independently associated with future ICH.

Association between substantia nigra degeneration and functional outcome in patients with basal ganglia infarction.

BACKGROUND AND PURPOSE: Cerebral infarction in the basal ganglia may cause secondary and delayed neuronal degeneration in the substantia nigra (SN). However, the clinical significance of SN degeneration remains poorly understood. METHODS: This retrospective observational study included patients with acute ischemic stroke in the basal ganglia on initial diffusion-weighted imaging who underwent follow-up diffusion-weighted imaging between 4 and 30 days after symptom onset. SN degeneration was defined as a hyperintensity lesion in the SN observed on diffusion-weighted imaging. We compared functional outcomes at 3 months between patients with and without SN degeneration. A poor outcome was defined as a score of 3-6 (functional dependence or death) on the modified Rankin Scale. RESULTS: Of 350 patients with basal ganglia infarction (median age = 74.0 years, 53.7% male), 125 (35.7%) had SN degeneration. The proportion of functional dependence or death was 79.2% (99/125 patients) in patients with SN degeneration, which was significantly higher than that in those without SN degeneration (56.4%, 127/225 patients, p < 0.001). SN degeneration was more frequent in patients with functional dependence or death (99/226 patients, 43.8%) than in those with functional independence (26/124 patients, 21.0%, p < 0.001). Multivariable logistic regression analysis showed a significant association between SN degeneration and functional dependence or death (odds ratio = 2.91, 95% confidence interval = 1.17-7.21, p = 0.021). CONCLUSIONS: The study showed that patients with degeneration of SN were associated with functional dependence or death at 3 months, suggesting that secondary degeneration is a predictor of poor stroke outcomes and a potential therapeutic target.

Preprocedural D-Dimer Level as a Predictor of First-Pass Recanalization and Functional Outcome in Endovascular Treatment of Acute Ischemic Stroke.

We aimed to evaluate the association between preprocedural D-dimer levels and endovascular and clinical outcomes. We retrospectively reviewed patients with acute intracranial large-vessel occlusion who underwent mechanical thrombectomy. Plasma D-dimer levels were measured immediately before the endovascular procedure. Endovascular outcomes included successful recanalization, first-pass recanalization (first-pass effect (FPE) and modified FPE (mFPE)), thrombus fragmentation, and the number of passes of the thrombectomy device. Clinical outcomes were assessed at 3 months using the modified Rankin Scale. A total of 215 patients were included. Preprocedural D-dimer levels were lower in patients with FPE (606.0 ng/mL [interquartile range, 268.0-1062.0]) than in those without (879.0 ng/mL [437.0-2748.0]; p = 0.002). Preprocedural D-dimer level was the only factor affecting FPE (odds ratio, 0.92 [95% confidence interval, 0.85-0.98] per 500 ng/mL; p = 0.022). D-dimer levels did not differ significantly based on successful recanalization and thrombus fragmentation. The number of passes of the thrombectomy device was higher (p = 0.002 for trend) and the puncture-to-recanalization time was longer (p = 0.044 for trend) as the D-dimer levels increased. Patients with favorable outcome had significantly lower D-dimer levels (495.0 ng/mL [290.0-856.0]) than those without (1189.0 ng/mL [526.0-3208.0]; p < 0.001). Preprocedural D-dimer level was an independent factor for favorable outcome (adjusted odds ratio, 0.88 [0.81-0.97] per 500 ng/mL; p = 0.008). In conclusion, higher preprocedural D-dimer levels were significantly associated with poor endovascular and unfavorable functional outcomes.

Clinical Benefit of First-Pass Recanalization Is Time-Dependent in Endovascular Treatment of Acute Ischemic Stroke.

Clinical benefit can be time-dependent even after first-pass recanalization (FPR) in endovascular treatment of acute stroke. This study aimed to evaluate the association between favorable outcome and FPR under a specific time frame. Patients who underwent mechanical thrombectomy were retrospectively reviewed. Recanalization status was categorized into four groups based on FPR and dichotomized time from groin puncture to recanalization (P-to-R time). Favorable outcomes were compared between groups. A total of 458 patients were included. As the cutoff of P-to-R time for favorable outcome was 30 min, recanalization status was categorized into FPR (+) with a P-to-R time ≤ 30 min (Group 1), FPR (-) with a P-to-R time ≤ 30 min (Group 2), FPR (+) with a P-to-R time > 30 min (Group 3), and FPR (-) with a P-to-R time > 30 min (Group 4). Favorable outcomes in Group 3 (37.5%) were significantly less frequent than those in Group 1 (60.4%, p = 0.029) and Group 2 (59.5%, p = 0.033) but were not significantly different from those in Group 4 (35.7%, p = 0.903). Compared to Group 1, Group 3 (adjusted odds ratio, 0.30 [95% confidence interval, 0.12-0.76]; p = 0.011) and Group 4 (0.25 [0.14-0.48]; p < 0.001) were adversely associated with favorable outcomes. FPR was associated with functional outcome in a time-dependent manner. Even for patients who have achieved FPR, their functional outcome might not be favorable if the P-to-R time is >30 min.

Coagulation Factor Expression and Composition of Arterial Thrombi in Cancer-Associated Stroke.

BACKGROUND: Cancer is associated with an increased risk of stroke. Tumor cells activate platelets, induce a coagulation cascade, and generate thrombin. The composition of thrombi may reflect the mechanism of thrombosis, aiding the determination of the treatment strategy. Here, we investigated the composition and expression of coagulation factors in the thrombi of patients with cancer-associated stroke. METHODS: Patients with stroke who underwent endovascular thrombectomy between September 2014 and June 2020 and whose cerebral thrombi were obtained were divided into those with cancer-associated stroke (cancer group) and propensity score-matched patients without cancer (control group), using 1:1 matching based on age and sex. Immunohistochemistry was performed of the thrombi, and the composition and expression of coagulation factors were compared between groups. RESULTS: Among the 320 patients who underwent endovascular thrombectomy and who had thrombi obtained, this study included 23 patients with cancer and 23 matched controls. In both groups, the median age was 65 years, and 12 patients (52.2%) were men. Platelet composition was significantly higher in the cancer group than in the control group (median [interquartile range], 51.3% [28.0%-61.4%] versus 9.5% [4.8%-14.0%]; P<0.001). Among coagulation factors, thrombin (26.2% [16.2%-52.7%] versus 4.5% [1.3%-7.2%]; P<0.001) and tissue factors (0.60% [0.34%-2.06%] versus 0.37% [0.22%-0.60%]; P=0.024) were higher and factor X was lower (1.25% [0.39%-3.60%] versus 2.33% [1.67%-4.48%]; P=0.034) in the cancer group. There was a positive correlation between thrombin and platelets in the cancer group (r=0.666; P=0.001) but not in the control group (r=-0.167; P=0.627). CONCLUSIONS: Cerebral thrombi in patients with cancer-associated stroke showed higher proportions of platelets, thrombin, and tissue factors, suggesting their key roles in arterial thrombosis in cancer and providing a therapeutic perspective for preventing stroke in patients with cancer-associated stroke.

Intensive vs Conventional Blood Pressure Lowering After Endovascular Thrombectomy in Acute Ischemic Stroke: The OPTIMAL-BP Randomized Clinical Trial.

Importance: Optimal blood pressure (BP) control after successful reperfusion with endovascular thrombectomy (EVT) for patients with acute ischemic stroke is unclear. Objective: To determine whether intensive BP management during the first 24 hours after successful reperfusion leads to better clinical outcomes than conventional BP management in patients who underwent EVT. Design, Setting, and Participants: Multicenter, randomized, open-label trial with a blinded end-point evaluation, conducted across 19 stroke centers in South Korea from June 2020 to November 2022 (final follow-up, March 8, 2023). It included 306 patients with large vessel occlusion acute ischemic stroke treated with EVT and with a modified Thrombolysis in Cerebral Infarction score of 2b or greater (partial or complete reperfusion). Interventions: Participants were randomly assigned to receive intensive BP management (systolic BP target <140 mm Hg; n = 155) or conventional management (systolic BP target 140-180 mm Hg; n = 150) for 24 hours after enrollment. Main Outcomes and Measures: The primary outcome was functional independence at 3 months (modified Rankin Scale score of 0-2). The primary safety outcomes were symptomatic intracerebral hemorrhage within 36 hours and death related to the index stroke within 3 months. Results: The trial was terminated early based on the recommendation of the data and safety monitoring board, which noted safety concerns. Among 306 randomized patients, 305 were confirmed eligible and 302 (99.0%) completed the trial (mean age, 73.0 years; 122 women [40.4%]). The intensive management group had a lower proportion achieving functional independence (39.4%) than the conventional management group (54.4%), with a significant risk difference (-15.1% [95% CI, -26.2% to -3.9%]) and adjusted odds ratio (0.56 [95% CI, 0.33-0.96]; P = .03). Rates of symptomatic intracerebral hemorrhage were 9.0% in the intensive group and 8.1% in the conventional group (risk difference, 1.0% [95% CI, -5.3% to 7.3%]; adjusted odds ratio, 1.10 [95% CI, 0.48-2.53]; P = .82). Death related to the index stroke within 3 months occurred in 7.7% of the intensive group and 5.4% of the conventional group (risk difference, 2.3% [95% CI, -3.3% to 7.9%]; adjusted odds ratio, 1.73 [95% CI, 0.61-4.92]; P = .31). Conclusions and Relevance: Among patients who achieved successful reperfusion with EVT for acute ischemic stroke with large vessel occlusion, intensive BP management for 24 hours led to a lower likelihood of functional independence at 3 months compared with conventional BP management. These results suggest that intensive BP management should be avoided after successful EVT in acute ischemic stroke. Trial Registration: ClinicalTrials.gov Identifier: NCT04205305.

Association of clot ultrastructure with clot perviousness in stroke patients.

Clot perviousness on computerized tomography (CT) is predictive of response to reperfusion therapy. This study aimed to determine the association of clot perviousness with ultrastructural features of clot in stroke patients undergoing endovascular thrombectomy. We quantitatively analyzed the ultrastructural components identified using scanning electron microscopy. The clot components were determined in the inner portions of the clots. Clot perviousness was assessed as thrombus attenuation increase (TAI) using noncontrast CT and CT angiography. We compared the association between the identified ultrastructural components and clot perviousness. The proportion of pores consisted of 3.5% on scanning electron microscopy images. The proportion of porosity in the inner portion was 2.5%. Among the ultrastructural components, polyhedrocytes were most commonly observed. The mean TAI was 9.3 ± 10.0 (median 5.6, interquartile range 1.1-14.3) Hounsfield units. TAI correlated positively with inner porosity (r = 0.422, p = 0.020). Among the ultrastructural clot components, TAI was independently associated with polyhedrocytes (B = - 0.134, SE = 0.051, p = 0.008). Clot perviousness is associated with porosity and the proportion of polyhdrocytes of clots.

Corrigendum: Clinical implications of atrial fibrillatioN detection using wearabLE devices in patients with cryptogenic stroke (CANDLE-AF) trial: Design and rationale.

[This corrects the article DOI: 10.3389/fcvm.2022.837958.].

Differential association between apolipoprotein B and LDL cholesterol and cerebral atherosclerosis according to pre-stroke statin use.

BACKGROUND AND AIMS: To reduce cardiovascular risk, low-density lipoprotein cholesterol (LDL-C) is the primary target of statin treatment, while apolipoprotein B (ApoB) is secondary. We investigated the association between atherosclerotic stenosis and LDL-C or ApoB levels and whether a difference in association exists according to pre-admission statin use in ischemic stroke patients. METHODS: This retrospective cross-sectional study included consecutive patients with acute ischemic stroke or transient ischemic attack who underwent lipid profile and angiographic testing. Patients were categorized into four groups according to stenosis location: normal, extracranial atherosclerotic stenosis (ECAS), intracranial atherosclerotic stenosis (ICAS), or ECAS + ICAS. Subgroup analyses were performed by pre-admission statin use. RESULTS: Of the 6338 patients included, 1980 (31.2%) were in the normal group, 718 (11.3%) in the ECAS group, 1845 (29.1%) in the ICAS group, and 1795 (28.3%) in the ECAS + ICAS group. Both LDL-C and ApoB levels were associated with every location of stenosis. A significant interaction was found between pre-admission statin use and LDL-C level (p for interaction <0.05). LDL-C was associated with stenosis only in statin-naïve patients, whereas ApoB was associated with ICAS, with or without ECAS, in both statin-naïve and statin-treated patients. ApoB also showed a consistent association with symptomatic ICAS in both statin-treated and statin-naïve patients, whereas LDL-C did not. CONCLUSIONS: ApoB was consistently associated with ICAS, particularly symptomatic stenosis, in both statin-naïve and statin-treated patients. The close association between ApoB levels and residual risk in statin-treated patients could be partially explained by these results.