Cancer Prediction With Machine Learning of Thrombi From Thrombectomy in Stroke: Multicenter Development and Validation.

BACKGROUND: We aimed to develop and validate machine learning models to diagnose patients with ischemic stroke with cancer through the analysis of histopathologic images of thrombi obtained during endovascular thrombectomy. METHODS: This was a retrospective study using a prospective multicenter registry which enrolled consecutive patients with acute ischemic stroke from South Korea who underwent endovascular thrombectomy. This study included patients admitted between July 1, 2017 and December 31, 2021 from 6 academic university hospitals. Whole-slide scanning was performed for immunohistochemically stained thrombi. Machine learning models were developed using transfer learning with image slices as input to classify patients into 2 groups: cancer group or other determined cause group. The models were developed and internally validated using thrombi from patients of the primary center, and external validation was conducted in 5 centers. The model was also applied to patients with hidden cancer who were diagnosed with cancer within 1 month of their index stroke. RESULTS: The study included 70 561 images from 182 patients in both internal and external datasets (119 patients in internal and 63 in external). Machine learning models were developed for each immunohistochemical staining using antibodies against platelets, fibrin, and erythrocytes. The platelet model demonstrated consistently high accuracy in classifying patients with cancer, with area under the receiver operating characteristic curve of 0.986 (95% CI, 0.983-0.989) during training, 0.954 (95% CI, 0.937-0.972) during internal validation, and 0.949 (95% CI, 0.891-1.000) during external validation. When applied to patients with occult cancer, the model accurately predicted the presence of cancer with high probabilities ranging from 88.5% to 99.2%. CONCLUSIONS: Machine learning models may be used for prediction of cancer as the underlying cause or detection of occult cancer, using platelet-stained immunohistochemical slide images of thrombi obtained during endovascular thrombectomy.

Patent Foramen Ovale and Risk of Recurrence in Stroke of Determined Etiology.

OBJECTIVE: Patent foramen ovale (PFO) is often found in stroke patients with determined etiologies. PFO may be the actual cause of stroke in some of them. We determined whether the risk of recurrent ischemic stroke differs with PFO status in stroke patients with determined etiologies. METHODS: This study included consecutive patients with stroke of determined etiology who underwent transesophageal echocardiography. We compared the rates of recurrent cerebral infarction in patients with versus without PFO, and according to PFO-Associated Stroke Causal Likelihood (PASCAL) classification. RESULTS: Of 2,314 included patients, 827 (35.7%) had PFO. During a median follow-up of 4.4 years, cerebral infarction recurred in 202 (8.7%). In multivariate modified Cox regression analyses, recurrence of infarction did not significantly differ between patients with PFO and those without PFO (hazard ratio [HR] = 0.86, 95% confidence interval [CI] = 0.64-1.17, p = 0.339). Interaction analysis showed a significant effect of PFO in patients aged <65 years (adjusted p for interaction = 0.090). PFO was independently associated with a decreased risk of recurrent infarction in patients younger than 65 years (HR = 0.41, 95% CI = 0.20-0.85, adjusted p = 0.016). Patients with probable PFO-associated stroke on the PASCAL classification had a significantly lower risk of recurrent infarction than those without PFO (HR = 0.31, 95% CI = 0.10-0.97, p = 0.044). INTERPRETATION: Considering the generally low risk of recurrence in PFO-associated stroke, PFO may be the actual cause of stroke in some patients with determined etiologies, especially younger patients or those with PFO features of probable PFO-associated stroke. ANN NEUROL 2022;92:596-606.

Lobeglitazone, a novel thiazolidinedione, for secondary prevention in patients with ischemic stroke: a nationwide nested case-control study.

INTRODUCTION: Ischemic stroke patients with diabetes are at high risk for recurrent stroke and cardiovascular complications. Pioglitazone, a type of thiazolidinedione, has been shown to reduce cardiovascular complications in patients with ischemic stroke and type 2 diabetes (T2D) or insulin resistance. Lobeglitazone is a novel thiazolidinedione agent that improves insulin resistance and has similar glycemic efficacy to pioglitazone. Using population-based health claims data, we evaluated whether lobeglitazone has secondary cardiovascular preventive effects in patients with ischemic stroke and T2D. METHODS: This study has a nested case-control design. From nationwide health claims data in Korea, we identified patients with T2D admitted for acute ischemic stroke in 2014-2018. Cases were defined who suffered the primary outcome (a composite of recurrent stroke, myocardial infarction, and all-cause death) before December 2020. Three controls were selected by incidence density sampling for each case from those who were at risk at the time of their case occurrence with exact matching on sex, age, the presence of comorbidities, and medications. As a safety outcome, we also evaluated the risk of heart failure (HF) according to the use of lobeglitazone. RESULTS: From the cohort of 70,897 T2D patients with acute ischemic stroke, 20,869 cases and 62,607 controls were selected. In the multivariable conditional logistic regression, treatment with lobeglitazone (adjusted OR 0.74; 95% CI 0.61-0.90; p = 0.002) and pioglitazone (adjusted OR 0.71; 95% CI 0.64-0.78; p < 0.001) were significantly associated with a lower risk for the primary outcome. In a safety outcome analysis for HF, treatment with lobeglitazone did not increase the risk of HF (adjusted OR 0.90; 95% CI 0.66-1.22; p = 0.492). CONCLUSIONS: In T2D patients with ischemic stroke, lobeglitazone reduced the risk of cardiovascular complications similar to that of pioglitazone without an increased risk of HF. There is a need for further studies on the cardioprotective role of lobeglitazone, a novel thiazolidinedione.

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.

Impact of Renal Function on Short-Term Outcome After Reperfusion Therapy in Patients With Ischemic Stroke.

BACKGROUND: A high and low estimated glomerular filtration rate (eGFR) could affect outcomes after reperfusion therapy for ischemic stroke. This study aimed to determine whether renal function based on eGFR affects mortality risk in patients with ischemic stroke within 6 months following reperfusion therapy. METHODS: This prospective registry-based cohort study included 2266 patients who received reperfusion therapy between January 2000 and September 2019 and were registered in the SECRET (Selection Criteria in Endovascular Thrombectomy and Thrombolytic Therapy) study or the Yonsei Stroke Cohort. A high and low eGFR were based on the Chronic Kidney Disease Epidemiology Collaboration equation and defined, respectively, as the 5th and 95th percentiles of age- and sex-specific eGFR. Occurrence of death within 6 months was compared among the groups according to their eGFR such as low, normal, or high eGFR. RESULTS: Of the 2266 patients, 2051 (90.5%) had a normal eGFR, 110 (4.9%) a low eGFR, and 105 (4.6%) a high eGFR. Patients with high eGFR were younger or less likely to have hypertension, diabetes, or atrial fibrillation than the other groups. Active cancer was more prevalent in the high-eGFR group. During the 6-month follow-up, there were 24 deaths (22.9%) in the high-eGFR group, 37 (33.6%) in the low-eGFR group, and 237 (11.6%) in the normal-eGFR group. After adjusting for variables with P<0.10 in the univariable analysis, 6-month mortality was independently associated with high eGFR (hazard ratio, 2.22 [95% CI, 1.36-3.62]; P=0.001) and low eGFR (HR, 2.29 [95% CI, 1.41-3.72]; P=0.001). These associations persisted regardless of treatment modality or various baseline characteristics. CONCLUSIONS: High eGFR as well as low eGFR were independently associated with 6-month mortality after reperfusion therapy. Kidney function could be considered a prognostic factor in patients with ischemic stroke after reperfusion therapy.

Cerebral Infarction Observed on Brain MRI in Unconscious Out-of-Hospital Cardiac Arrest Survivors: A Pilot Study.

BACKGROUND: Cumulative evidence regarding the use of brain magnetic resonance imaging (MRI) for predicting prognosis of unconscious out-of-hospital cardiac arrest (OHCA) survivors treated with targeted temperature management (TTM) is available. Theoretically, these patients are at a high risk of developing cerebral infarction. However, there is a paucity of reports regarding the characteristics of cerebral infarction in this population. Thus, we performed a pilot study to identify the characteristics and risk factors of cerebral infarction and to evaluate whether this infarction is associated with clinical outcomes. METHODS: A single-center, retrospective, registry-based cohort study was conducted at Severance Hospital, a tertiary center. Unconscious OHCA survivors were registered and treated with TTM between September 2011 and December 2015. We included patients who underwent brain MRI in the first week after the return of spontaneous circulation. We excluded patients who underwent any endovascular interventions to focus on "procedure-unrelated" cerebral infarctions. We assessed hypoxic-ischemic encephalopathy (HIE) and procedure-unrelated cerebral infarction separately on MRI. Patients were categorized into the following groups based on MRI findings: HIE (-)/infarction (-), infarction-only, and HIE (+) groups. Conventional vascular risk factors showing p < 0.05 in univariate analyses were entered into multivariate logistic regression. We also evaluated if the presence of this procedure-unrelated cerebral infarction lesion or HIE was associated with a poor clinical outcome at discharge, defined as a cerebral performance category of 3-5. RESULTS: Among 71 unconscious OHCA survivors who completed TTM, underwent MRI, and who did not undergo endovascular interventions, 14 (19.7%) patients had procedure-unrelated cerebral infarction based on MRI. Advancing age [odds ratio (OR) 1.11] and atrial fibrillation (OR 5.78) were independently associated with the occurrence of procedure-unrelated cerebral infarction (both p < 0.05). There were more patients with poor clinical outcomes at discharge in the HIE (+) group (88.1%) than in the infarction-only (30.0%) or HIE (-)/infarction (-) group (15.8%) (p < 0.001). HIE (+) (OR 38.69, p < 0.001) was independently associated with poor clinical outcomes at discharge, whereas infarction-only was not (p > 0.05), compared to HIE (-)/infarction (-). CONCLUSIONS: In this pilot study, procedure-unrelated cerebral infarction was noted in approximately one-fifth of unconscious OHCA survivors who were treated with TTM and underwent MRI. Older age and atrial fibrillation might be associated with the occurrence of procedure-unrelated cerebral infarction, and cerebral infarction was not considered to be associated with clinical outcomes at discharge. Considering that the strict exclusion criteria in this pilot study resulted in a highly selected sample with a relatively small size, further work is needed to verify our findings.

Advanced Liver Fibrosis Predicts Unfavorable Long-Term Prognosis in First-Ever Ischemic Stroke or Transient Ischemic Attack.

INTRODUCTION: There are a limited number of studies investigating the relationship between the degree of liver fibrosis and the long-term prognosis, especially ischemic stroke (IS) recurrence, in first-ever IS or transient ischemic attack (TIA). OBJECTIVE: We investigated whether there are differences in the long-term all-cause and cardiovascular mortalities and IS recurrence based on the degree of liver fibrosis in first-ever IS or TIA. METHODS: This analysis included 2,504 patients with first-ever IS or TIA recruited from a prospective stroke cohort. Liver fibrosis was predicted using the fibrosis-4 (FIB-4) index, and advanced fibrosis was defined as an FIB-4 index of >3.25. Using Cox regression models, we compared the all-cause and cardiovascular mortalities and IS recurrence. As measures for the additive predictive value of the FIB-4 index for prediction of all-cause mortality, the integrated area under the receiver operating characteristic curve (iAUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used. RESULTS: There were 231 (9.2%) patients with advanced fibrosis. During a median follow-up of 1.2 years, the cumulative all-cause and cardiovascular mortalities were 6.4 and 1.9%, and IS recurrence was observed in 5.3%. The advanced fibrosis was associated with an increased risk of all-cause mortality (hazard ratio [HR] = 3.98, 95% confidence interval [CI] = 2.40-6.59), cardiovascular mortality (HR = 4.48, 95% CI = 1.59-12.65), and IS recurrence (HR = 1.95, 95% CI = 1.05-3.65). Adding the FIB-4 index to the model consisting of traditional cardiovascular risk factors improved the predictive accuracy for all-cause mortality as measured using the iAUC (from 0.7594 to 0.7729) and for all-cause mortality at 1 year as measured using the NRI (38.6%) and IDI (0.037). CONCLUSIONS: The burden of liver fibrosis is associated with unfavorable long-term prognosis, including recurrent IS, in first-ever IS or TIA.

Liver Fibrosis, Not Steatosis, Associates with Long-Term Outcomes in Ischaemic Stroke Patients.

BACKGROUND: To investigate whether there are differences in long-term all-cause and cardiovascular mortality according to the burden of liver fibrosis or steatosis in patients with ischaemic stroke or transient ischaemic attack (TIA). -Methods: Consecutive patients with acute ischaemic stroke or TIA who underwent transient elastography (TE) from January 2014 to December 2014 were considered eligible. The influence of liver fibrosis or steatosis, assessed via TE, on long-term outcomes was investigated using Cox proportional hazard models. RESULTS: Among 395 patients included in this study, there were 37 (9%) patients with significant fibrosis (> 8.0 kPa) and 164 (41.5%) patients with fatty liver (> 250 dB/m). During the follow-up period (median 2.7 years), all-cause and cardiovascular mortality occurred in 28 (7.1%) and 20 (5.1%) patients. On multivariate analyses, significant liver fibrosis was independently associated with increased risk of all-cause (hazard ratio [HR] 8.14, 95% CI 3.03-21.90, p < 0.001) and cardiovascular (HR 4.29, 95% CI 1.10-16.73, p = 0.036) mortality, whereas fatty liver was not (all p > 0.05). CONCLUSIONS: This study found that the burden of liver fibrosis but not that of steatosis, assessed via TE, was an independent predictor of all-cause and cardiovascular mortality during long-term follow-up in patients with ischaemic stroke.

Risk of thromboembolism according to statin treatment in patients with cancer: A nationwide nested case-control study.

BACKGROUND: Thromboembolic events exhibit increased prevalence in patients with cancer and can negatively affect prognoses. We investigated whether statin treatment would reduce thromboembolic risk in patients with cancer. METHODS: We conducted a nested case-control study using a Korean nationwide health claims database. The study included patients newly diagnosed with cancer without a prior history of cardiovascular disease between 2014 and 2016. Cases who developed arterial thromboembolism (ATE) or venous thromboembolism (VTE) after cancer diagnosis and three individually matched controls were selected. Conditional logistic regression was used to assess the association between thromboembolic risk and statin therapy after cancer diagnosis. RESULTS: Among 455,805 newly diagnosed patients with cancer followed for a mean of 4.3 ± 2.0 years, 22,249 patients developed thromboembolic events (ATE: 6341, VTE: 15,908), resulting in an incidence rate of 1133 per 100,000 person-years. The nested case-control study included 21,289 cases with thromboembolic events and 63,867 controls. Statin use was less frequent in the case group (18.0 % vs. 23.7 %). Statin treatment was associated with a lower risk of thromboembolic events (adjusted odds ratio [OR] 0.70; 95 % confidence interval [CI] 0.67-0.73). This association was observed for both ATE (adjusted OR 0.68; 95 % CI 0.63-0.74) and VTE (adjusted OR 0.71; 95 % CI 0.67-0.75). Longer statin use and better adherence were also associated with lower risk for thromboembolic events. Statin treatment was significantly associated with fewer thromboembolic events in most cancer types. CONCLUSIONS: Statin use was associated with lower risk for thromboembolic events in patients newly diagnosed with cancer.

Effect of Statins for Primary Prevention of Cardiovascular Disease According to the Fatty Liver Index.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is associated with increased risk of cardiovascular disease (CVD). We investigated the primary preventive effect of statins on CVD according to the level of fatty liver index (FLI), which is a marker of NAFLD. METHODS: We conducted a nested case-control study on the basis of a nationwide health screening cohort in Korea. The participants were divided into tertiles (T1, T2, and T3) according to their FLI score. Cases were defined as individuals who developed CVD (composite of myocardial infarction and stroke). Three controls were matched to each case and multivariable conditional logistic regression analysis was performed. RESULTS: Within a cohort of 206,263 participants without prior CVD, 7044 individuals suffered the primary outcome. For the nested case-control study, we selected these 7044 cases along with their corresponding 20,641 matched controls. Individuals in the T3 tertiles of FLI had a higher risk of CVD than those in the T1 tertile [adjusted odds ratio (OR) 1.30; 95% confidence interval (CI) 1.20-1.40, P < 0.001]. In sub-analyses based on FLI tertiles, statin therapy was associated with a lower risk of CVD (adjusted OR 0.72; 95% CI 0.61-0.85, P < 0.001) in the T3 tertile but not in the T1 and T2 tertiles. CONCLUSIONS: Statin therapy was associated with a reduced risk of CVD in individuals with high FLI but not in those with low FLI. Further research is needed to determine the pathophysiologic mechanism between statin and NAFLD.

Discontinuation of antiplatelet therapy after stent-assisted coil embolisation of cerebral aneurysm: a nationwide cohort study.

INTRODUCTION: Stent-assisted coil embolisation (SACE) for the treatment of unruptured cerebral aneurysms has been increasingly used. Long-term advantages of antiplatelet therapy (APT) post-SACE treatment are still not well understood. We investigated the long-term effects of APT on clinical prognosis after SACE. PATIENTS AND METHODS: We conducted a retrospective study using nationwide health insurance claims data from South Korea, including patients with cerebral aneurysm treated with SACE from January 2009 to December 2020. The study outcomes consisted of the occurrence of cerebral infarction and major haemorrhage. To evaluate the impact of APT, we employed a multivariable time-dependent Cox proportional hazards regression model for each of the three distinct periods: 1-12 months, 12-24 months and >24 months after SACE. RESULTS: This study included 17 692 unruptured cerebral aneurysm patients treated with SACE. During the mean follow-up of 4.2 years, there were 379 (2.1%) patients with cerebral infarction and 190 (1.1%) patients with major haemorrhage. The percentage of patients receiving APT was 79.5% at 1 year, which gradually decreased to 58.3% at 2 years after SACE. APT was beneficial in preventing cerebral infarction within 12 months after SACE (adjusted HR (aHR) 0.56; 95% CI, 0.35 to 0.89; p=0.014). After 12 months, this association was not evident. APT increased the risk of haemorrhage after 24 months (aHR 1.76; 95% CI 1.11 to 2.87; p=0.016). DISCUSSION AND CONCLUSION: Our findings suggest that in patients with unruptured cerebral aneurysm treated with SACE, the reasonable duration of APT for preventing cerebral infarction might be 1 year after SACE.

Proton Pump Inhibitor for Gastrointestinal Bleeding in Patients with Myocardial Infarction on Dual-Antiplatelet Therapy: A Nationwide Cohort Study.

BACKGROUND: Guidelines provide various recommendations for the use of proton pump inhibitors (PPI) to prevent upper gastrointestinal (UGI) bleeding in acute myocardial infarction (MI) treatment with dual antiplatelet therapy (DAPT). We evaluated the effects of PPIs in reducing the risk of severe UGI bleeding in patients with MI receiving DAPT. METHODS: This retrospective cohort study included patients admitted for acute MI between 2014 and 2018, based on a nationwide health claims database in Korea. Primary outcome was admission for severe UGI bleeding requiring transfusion within 1 year of MI diagnosis. A multivariable Cox regression model was used to calculate the association between PPI use and severe UGI bleeding risk. RESULTS: Of 100,556 patients with MI on DAPT (mean age, 63.7 years; 75.4% men), 37% were prescribed PPIs. Based on risk assessment for UGI bleeding, among 6,392 (6.4%) high-risk and 94,164 (93.6%) low-risk patients, 50.5% and 35.8% received PPIs, respectively. Overall, 0.5% of the patients experienced severe UGI bleeding within 1 year after MI. The use of PPI was associated with a reduced risk of severe UGI bleeding (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.47-0.70; P < 0.001). The benefits of PPIs were consistent in high-risk (HR, 0.71; 95% CI, 0.45-1.13; P = 0.147) and low-risk (HR, 0.54; 95% CI, 0.43-0.68; P < 0.001) patients (P for interaction = 0.481). CONCLUSIONS: Among Korean patients with MI receiving DAPT, PPIs were underutilized, even among those at high risk of severe UGI bleeding. Nonetheless, PPI use reduced severe UGI bleeding in low- and high-risk groups.

Duration of dual-antiplatelet therapy after stent-assisted coil for unruptured intracranial aneurysm: A nationwide cohort study.

BACKGROUND: Stent-assisted coil (SAC) is increasingly used to treat unruptured intracranial aneurysm (UIA). However, the optimal duration of dual-antiplatelet therapy (DAPT) after SAC insertion remains unknown. AIM: To assess the time-dependent effect of DAPT on the risk of ischemic and hemorrhagic complications after SAC. METHODS: This is a retrospective cohort study among patients with UIA treated with SAC using the nationwide health claims database in South Korea between 2009 and 2020. Multivariate Cox regression analysis was used, which included the use of DAPT as a time-dependent variable. The effect of DAPT was investigated for each period of "within 90 days," "91 to 180 days," "181 to 365 days," and "366 to 730 days" after SAC. The primary outcome was a composite of ischemic stroke and major bleeding in each period within two years after SAC. RESULTS: Of the 15,918 patients, mean age at SAC was 57.6 ± 10.8 years, and 3815 (24.0%) were men. The proportion of patients on DAPT was 79.4% at 90 days, 58.3% at 180 days, and 28.9% at 1 year after SAC. During the 2 years after SAC, the primary composite outcome occurred in 356 patients (2.2%). DAPT significantly reduced the primary composite outcome within 90 days after SAC (adjusted hazard ratio (aHR), 0.44; 95% confidence interval (CI), 0.28-0.69; p < 0.001); however, this was not the case after 90 days (all p > 0.05). DAPT reduced ischemic stroke risk within 90 days (aHR, 0.31; 95% CI 0.18-0.54; p < 0.001), and 91 to 180 days after SAC (aHR 0.40; 95% CI 0.18-0.88; p = 0.022); however, after 180 days, DAPT was no longer beneficial. CONCLUSIONS: In patients with UIA treated with SAC, 3 months of DAPT was associated with a decreased risk of the composite of ischemic and hemorrhagic complications.

Long-term outcomes of patients with embolic stroke of undetermined source according to subtype.

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.

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.

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.

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.

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 management 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 hours 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 hours 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 OR 0.33, 95% 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 hours resulted in a reduced chance of functional independence at 3 months and did not reduce symptomatic intracerebral hemorrhage following successful reperfusion.

Association between statin therapy and the risk of stroke in patients with moyamoya disease: a nationwide cohort study.

BACKGROUND AND OBJECTIVE: Knowledge regarding the pharmacological treatment for moyamoya disease (MMD), a chronic and progressive cerebrovascular disease conferring greater stroke risk, is limited. In the present study, whether statin therapy is associated with a reduced risk of stroke in patients with MMD was investigated. METHODS: This was a retrospective cohort study in which the occurrence of stroke in patients with newly diagnosed MMD was investigated using the nationwide health insurance database in Korea from January 2007 to March 2021. A multivariable Cox proportional hazards regression model was constructed for stroke, in which statin therapy after MMD diagnosis was treated as a time-dependent variable. Adjustment was done for sex, age, presence of comorbidities, concurrent stroke, revascularisation surgery and treatment with antiplatelets. RESULTS: The present study included 13 373 newly diagnosed patients with MMD; 40.8% had a concurrent stroke at the time of MMD diagnosis. During the mean follow-up of 5.1±3.3 years, 631 patients (4.7%) suffered a stroke event (haemorrhagic stroke: 458 patients, ischaemic stroke: 173 patients). Statin therapy after MMD diagnosis was significantly associated with a reduced risk of stroke (adjusted HR 0.74; 95% CI 0.60 to 0.91, p=0.004). In the secondary outcome analysis, the risk of haemorrhagic stroke (adjusted HR 0.74; 95% CI 0.58 to 0.95, p=0.018) and ischaemic stroke (adjusted HR 0.75; 95% CI 0.52 to 1.08, p=0.124) were reduced with the statin treatment. Taking statins was also associated with a lower risk of all-cause mortality (adjusted HR 0.47; 95% CI 0.33 to 0.67, p<0.001). CONCLUSION: In patients with MMD, statin therapy was associated with a reduced risk of subsequent stroke. The findings indicate statin treatment may be beneficial for patients with MMD, however the results should be confirmed in randomised controlled trials.

Statin Treatment on Cardiovascular Risk After Retinal Artery Occlusion: A Historical Cohort Study.

INTRODUCTION: Retinal artery occlusion (RAO) is a major cause of acute visual loss and patients with RAO have an increased risk for subsequent cardiovascular events. However, there is little evidence of whether the use of statins is associated with the prevention of cardiovascular events in patients with RAO. We investigated whether statin treatment in patients with RAO is associated with a lower risk of cardiovascular events. METHODS: This study was a historical cohort study with nested case-control analysis. Using the nationwide health insurance claims database in Korea, we retrospectively established a cohort of newly diagnosed RAO patients without prior cardiovascular events between January 2008 and March 2020. We defined the case group as those who had cardiovascular events (stroke or myocardial infarction) and the control group as RAO patients without primary outcome matched by sex, age, comorbidities, and duration of follow-up (1:2 incidence density sampling). Conditional logistic regression was performed. RESULTS: Among 13,843 patients newly diagnosed with RAO, 1030 patients had cardiovascular events (mean follow-up period of 6.4 ± 3.7 years). A total of 957 cases were matched to 1914 controls. Throughout the study period, the proportion of patients taking statin was less than half. Statin treatment after RAO was associated with a low risk of cardiovascular events (adjusted OR, 0.637; 95% CI 0.520-0.780; P < 0.001). A longer duration of statin exposure was associated with a lower cardiovascular risk. CONCLUSIONS: In patients with newly diagnosed RAO, treatment with statins, particularly long-term use, was associated with a low risk of future cardiovascular events.