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

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.

In hagfish and lampreys, two representative jawless vertebrates, the humoral immunity is directly mediated by variable lymphocyte receptors B (VLRBs). Both monomeric VLRBs are structurally and functionally similar, but their C-terminal tails differ: lamprey VLRB has a Cys-rich tail that forms disulfide-linked pentamers of dimers, contributing to its multivalency, whereas hagfish VLRB has a superhydrophobic tail of unknown structure. Here, we reveal that VLRBs obtained from hagfish plasma have a globular-shaped multimerized form (approximately 0.6 to 1.7 MDa) that is generated by hydrophobic clustering instead of covalent linkage. Electron microscopy (EM) and single-particle analysis showed that the multimerized VLRBs form globular-shaped clusters with an average diameter of 28.7 ± 2.2 nm. The presence of VLRBs in the complex was confirmed by immune-EM analysis using an anti-VLRB antibody. Furthermore, the hydrophobic hagfish C-terminus (HC) was capable of triggering multimerization and directing the cellular surface localization via a glycophosphatidylinositol linkage. Our results strongly suggest that the hagfish VLRB forms a previously unknown globular-shaped antibody. This novel identification of a structurally unusual VLRB complex may suggest that the adaptive immune system of hagfish differs from that of lamprey.

Vascular aging phenotype may be useful in predicting stroke prognosis. In the present study, the relationship between vascular aging phenotypes and outcomes after acute ischemic stroke was investigated. The study included consecutive patients with acute ischemic stroke who had brachial-ankle pulse wave velocity (baPWV) measured to assess vascular aging phenotype. The 2.5th and 97.5th percentile age-specific baPWVs were used as cutoffs to define supernormal vascular aging (SUPERNOVA) and early vascular aging (EVA), respectively, and the remainder was considered normal vascular aging (NVA). A total of 2738 patients were enrolled and followed for a median of 38.1 months. The mean age was 67.02 years and 1633 were male. EVA was 67, NVA was 2605, and SUPERNOVA was 66. Compared with NVA, multivariable logistic regression showed EVA was associated with poor functional outcome (modified Rankin Scale ≥ 3) at 3 months (odds ratio 2.083, 95% confidence interval 1.147‒3.783). Multivariable Cox regression showed EVA was associated with all-cause mortality (hazard ratio 2.320, 95% confidence interval 1.283‒4.197). EVA was associated with poor functional outcome and all-cause mortality after acute ischemic stroke, especially when diabetes or atrial fibrillation coexisted. These findings indicate the vascular aging phenotype, notably EVA, can aid in identifying high-risk stroke patients.

The prognosis of patients with embolic stroke of undetermined source (ESUS) may vary according to the underlying cause. Therefore, we aimed to divide ESUS into subtypes and assess the long-term outcomes. Consecutive patients with acute ischemic stroke who underwent a comprehensive workup, including transesophageal echocardiography and prolonged electrocardiography monitoring, were enrolled. We classified ESUS into minor cardioembolic (CE) ESUS, arteriogenic ESUS, two or more causes ESUS, and no cause ESUS. Arteriogenic ESUS was sub-classified into complex aortic plaque (CAP) ESUS and non-stenotic (< 50%) relevant artery plaque (NAP) ESUS. A total of 775 patients were enrolled. During 1286 ± 748 days follow-up, 116 major adverse cardiovascular events (MACE) occurred (4.2 events/100 patient-years). Among the ESUS subtypes, CAP ESUS was associated with the highest MACE frequency (9.7/100 patient-years, p = 0.021). Cox regression analyses showed that CAP ESUS was associated with MACE (hazard ratio 2.466, 95% confidence interval 1.305–4.660) and any stroke recurrence (hazard ratio 2.470, 95% confidence interval, 1.108–5.508). The prognosis of ESUS varies according to the subtype, with CAP ESUS having the worst prognosis. Categorizing ESUS into subtypes could improve patient care and refine clinical trials.

Malignant middle cerebral artery infarction (MMI) is associated with a high incidence of severe disability and mortality. Decompressive hemicraniectomy has become a recognized treatment that can improve the prognosis for patients if performed within a certain time window. Nevertheless, despite this intervention, a mortality rate of approximately 20–40% persists following the surgery. The trends and clinical implications of intracranial pressure (ICP) in these situations remain unclear. We aimed to investigate whether intracranial pressure (ICP) trends are associated with clinical outcomes in patients undergoing decompressive hemicraniectomy for MMI. This retrospective cohort study included consecutive patients with MMI who underwent decompressive craniectomy and received ICP monitoring after surgery. Using a linear mixed model, we categorized the patients into ICP increase and decrease groups based on the ICP values obtained over 192 h. We then compared the proportion of 3-month favorable outcomes (modified Rankin Scale of 0−4) and mortality rates between these groups. Of 112 MMI patients who underwent decompressive hemicraniectomy, 66 (58.9%) received invasive ICP monitoring. ICP monitoring was performed for a median of 146.5 h (IQR 72.5–181.8). Among the 66 patients, 37 (56.1%) were in the ICP increase group, and 29 (43.9%) were in the ICP decrease group. During the monitoring period, the initial monitored ICP and peak ICP did not significantly differ between the ICP increase and decrease groups. However, the ICP trend was significantly different between the two groups (P < 0.001). In multivariable logistic regression analyses, the ICP increase group had a significantly lower proportion of 3-month favorable outcomes compared to the ICP decrease group (adjusted OR 0.11; 95% CI, 0.01–0.59; P = 0.019), and significantly higher mortality in the intensive care unit (adjusted OR 6.98; 95% CI, 1.37–54.6; P = 0.031). In MMI patients, continuous ICP monitoring could be useful for detecting those with an increasing ICP trend that may be associated with unfavorable clinical outcomes.