Effectiveness, utilisation and cost associated with implantable loop recorders versus external monitors after ischaemic or cryptogenic stroke.

OBJECTIVE: Implantable loop recorders (ILRs) are increasingly used for long-term rhythm monitoring after ischaemic and cryptogenic stroke, with the goal of detecting atrial fibrillation (AF) and subsequent initiation of oral anticoagulation to reduce risk of adverse clinical outcomes. There is a need to determine the effectiveness of different rhythm monitoring strategies in this context. METHODS: We conducted a retrospective cohort analysis of individuals with commercial and Medicare Advantage insurance in Optum Labs Data Warehouse who had incident ischaemic or cryptogenic stroke and no prior cardiovascular implantable electronic device from 1 January 2016 to 30 June 2021. Patients were stratified by rhythm monitoring strategy: ILR, long-term continuous external cardiac monitor (>48 hours to 30 days) or Holter monitor (≤48 hours). The primary outcome was risk-adjusted all-cause mortality at 12 months. Secondary outcomes included new diagnosis of AF and oral anticoagulation, bleeding, and costs. RESULTS: Among 48 901 patients with ischaemic or cryptogenic stroke, 9235 received an ILR, 29 103 long-term continuous external monitor and 10 563 Holter monitor only. Mean age was 69.9 (SD 11.9) years and 53.5% were female. During the 12-month follow-up period, patients who received ILRs compared with those who received long-term continuous external monitors had a higher odds of new diagnosis of AF and oral anticoagulant initiation (adjusted OR 2.27, 95% CI 2.09 to 2.48). Compared with patients who received long-term continuous external monitors, those who received ILRs had similar 12-month mortality (HR 1.00; 95% CI 0.89 to 1.12), with approximately $13 000 higher costs at baseline (including monitor cost) and $2500 higher costs during 12-month follow-up. CONCLUSIONS: In this large real-world study of patients with ischaemic or cryptogenic stroke, ILR placement resulted in more diagnosis of AF and initiation of oral anticoagulation, but no difference in mortality compared with long-term continuous external monitors.

Association of large core middle cerebral artery stroke and hemorrhagic transformation with hospitalization outcomes.

Historically, investigators have not differentiated between patients with and without hemorrhagic transformation (HT) in large core ischemic stroke at risk for life-threatening mass effect (LTME) from cerebral edema. Our objective was to determine whether LTME occurs faster in those with HT compared to those without. We conducted a two-center retrospective study of patients with ≥ 1/2 MCA territory infarct between 2006 and 2021. We tested the association of time-to-LTME and HT subtype (parenchymal, petechial) using Cox regression, controlling for age, mean arterial pressure, glucose, tissue plasminogen activator, mechanical thrombectomy, National Institute of Health Stroke Scale, antiplatelets, anticoagulation, temperature, and stroke side. Secondary and exploratory outcomes included mass effect-related death, all-cause death, disposition, and decompressive hemicraniectomy. Of 840 patients, 358 (42.6%) had no HT, 403 (48.0%) patients had petechial HT, and 79 (9.4%) patients had parenchymal HT. LTME occurred in 317 (37.7%) and 100 (11.9%) had mass effect-related deaths. Parenchymal (HR 8.24, 95% CI 5.46-12.42, p < 0.01) and petechial HT (HR 2.47, 95% CI 1.92-3.17, p < 0.01) were significantly associated with time-to-LTME and mass effect-related death. Understanding different risk factors and sequelae of mass effect with and without HT is critical for informed clinical decisions.

Endovascular Therapy and Outcomes Among Patients With Very Large Ischemic Core Stroke.

Importance: The association of endovascular therapy (EVT) with outcomes is unclear for patients with very low Alberta Stroke Program Early Computed Tomography Score (ASPECTS) within 24 hours of stroke onset. Objective: To explore the association of EVT with functional and safety outcomes among patients with ASPECTS of 0 to 2 scored with noncontrast computed tomography. Design, Setting, and Participants: This cohort study used data from an ongoing, prospective, observational, nationwide registry including all patients treated at 38 stroke centers in China with an occlusion in the internal carotid artery or M1 or M2 segment of the middle cerebral artery within 24 hours of witnessed symptom onset. Patients with ASPECTS of 0 to 2 between November 1, 2021, and February 8, 2023, were included in analysis. Data were analyzed October to November 2023. Exposures: EVT vs standard medical treatment (SMT). Main Outcomes and Measures: The primary outcome was favorable functional outcome, defined as modified Rankin Scale score (mRS) of 0 to 3, at 90 days. Safety outcomes included symptomatic intracerebral hemorrhage (sICH) within 48 hours and mortality at 90 days. Results: A total of 245 patients (median [IQR] age, 71 [63-78] years; 118 [48%] women) with ASPECTS of 0 to 2 were included, of whom 111 patients (45.1%) received SMT and 135 patients (54.9%) received EVT. The EVT group had significantly greater odds of favorable functional outcome at 90 days than the SMT group (30 patients [22.2%] vs 11 patients [9.9%]; P = .01; adjusted odds ratio [aOR], 3.07 [95% CI, 1.29-7.31]; P = .01). Patients in the EVT group, compared with the SMT group, had significantly greater odds of any ICH (56 patients [41.5%] vs 16 patients [11.4%]; P < .001; aOR, 4.27 [95% CI, 2.19-8.35]; P < .001) and sICH (24 patients [17.8%] vs 1 patient [0.9%]; P < .001; aOR, 23.07 [95% CI, 2.99-177.79]; P = .003) within 48 hours. There were no differences between groups for 90-day mortality (80 patients [59.3%] vs 59 patients [53.2%]; P = .34; aOR, 1.38 [95% CI, 0.77-2.47]; P = .28). The results remained robust in the propensity score-matched analysis. Conclusions and Relevance: In this cohort study of patients with very low ASPECTS based on NCCT within 24 hours of stroke onset, those treated with EVT had higher odds of a favorable functional outcome compared with those who received SMT. Randomized clinical trials are needed to assess these findings.

Long-Term Clinical Implications of High-Risk Cardiac Computed Tomography Findings in Patients With Acute Ischemic Stroke.

BACKGROUND: Cardiac computed tomography (CT) acquired during the initial acute stroke imaging protocol (acute cardiac CT) is increasingly used to screen for cardioembolism, but information on the long-term clinical implications of its findings is lacking. METHODS AND RESULTS: We performed a prospective, single-center cohort study in which consecutive patients with ischemic stroke underwent ECG-gated acute cardiac CT and were followed up for 2 years. The primary outcome was functional outcome assessed using the modified Rankin Scale. Secondary outcomes were death and occurrence of major adverse cardiovascular events (composite of recurrent ischemic stroke, myocardial infarction, and cardiovascular death). We compared patients with and without a high-risk structural source of embolism on acute cardiac CT. Of 452 included patients, 55 (12.2%) had a high-risk source of embolism, predominantly cardiac thrombi (38 patients) and signs of endocarditis (8 patients). Follow-up at 2 years was complete for 430 (95.1%) patients. Patients with a high-risk source of embolism had a worse functional outcome (median modified Rankin Scale, 6 [IQR, 2-6] versus 2 [IQR, 1-5]; adjusted common odds ratio, 2.92 [95% CI, 1.62-5.25]), increased mortality rate (52.7% versus 23.7%; adjusted hazard ratio [HR], 3.28 [95% CI, 1.94-5.52]), and major adverse cardiovascular events (38.9% versus 17.5%; adjusted HR, 3.20 [95% CI, 1.80-5.69]). A high-risk source of embolism was not associated with recurrent ischemic stroke (11.1% versus 9.6%; adjusted HR, 1.30 [95% CI, 0.49-3.44]). CONCLUSIONS: Structural high-risk sources of embolism on acute cardiac CT in patients with ischemic stroke were associated with poor long-term functional outcome and occurrence of major adverse cardiovascular events but not with recurrent stroke.

Impact of Vaccination Status on Outcome of Patients With COVID-19 and Acute Ischemic Stroke Undergoing Mechanical Thrombectomy.

BACKGROUND: Data on impact of COVID-19 vaccination and outcomes of patients with COVID-19 and acute ischemic stroke undergoing mechanical thrombectomy are scarce. Addressing this subject, we report our multicenter experience. METHODS AND RESULTS: This was a retrospective analysis of patients with COVID-19 and known vaccination status treated with mechanical thrombectomy for acute ischemic stroke at 20 tertiary care centers between January 2020 and January 2023. Baseline demographics, angiographic outcome, and clinical outcome evaluated by the modified Rankin Scale score at discharge were noted. A multivariate analysis was conducted to test whether these variables were associated with an unfavorable outcome, defined as modified Rankin Scale score >3. A total of 137 patients with acute ischemic stroke (48 vaccinated and 89 unvaccinated) with acute or subsided COVID-19 infection who underwent mechanical thrombectomy attributable to vessel occlusion were included in the study. Angiographic outcomes between vaccinated and unvaccinated patients were similar (modified Thrombolysis in Cerebral Infarction ≥2b: 85.4% in vaccinated patients versus 86.5% in unvaccinated patients; P=0.859). The rate of functional independence (modified Rankin Scale score, ≤2) was 23.3% in the vaccinated group and 20.9% in the unvaccinated group (P=0.763). The mortality rate was 30% in both groups. In the multivariable analysis, vaccination status was not a significant predictor for an unfavorable outcome (P=0.957). However, acute COVID-19 infection remained significant (odds ratio, 1.197 [95% CI, 1.007-1.417]; P=0.041). CONCLUSIONS: Our study demonstrated no impact of COVID-19 vaccination on angiographic or clinical outcome of COVID-19-positive patients with acute ischemic stroke undergoing mechanical thrombectomy, whereas worsening attributable to COVID-19 was confirmed.

The Relationship between Neutrophil-Lymphocyte Ratios with Nutritional Status, Risk of Nutritional Indices, Prognostic Nutritional Indices and Morbidity in Patients with Ischemic Stroke.

Background: In recent years, whole blood parameters and derivatives have been used as prognostic criteria in the course of various diseases. The aim of this study was to evaluate the relationship between parameters such as the neutrophil-lymphocyte ratio (NLR), the systemic immune-inflammation index (SII), the prognostic nutritional index (PNI), controlling nutritional status (CONUT) score, nutritional risk index (NRI) and immunonutrition status and disease activity in patients with ischemic stroke of the small-vessel, large-vessel and other etiologies. Methods: We retrospectively evaluated the records of 1454 consecutive ischemic stroke patients hospitalized in the emergency department of Gaziosmanpasa Education and Research Hospital from 2019 to 2023. Results: Of the 1350 patients with ischemic stroke included in the study, 58.8% had small-vessel disease, 29.3% had large-vessel disease and 11.9% had other etiologies. There was a significant difference between the three etiology groups for PNI and CONUT. The mean of PNI was 47.30 ± 8.06 in the other etiology group, 37.25 ± 7.23 in the small-vessel group, and 34.78 ± 8.16 in the large-vessel disease group. The mean of CONUT was 5.49 ± 1.20 in the small-vessel group, 5.12 ± 1.46 in the large-vessel group and 4.22 ± 1.11 in the other etiology group. In addition, CONUT and PNI were also found to be independent risk factors for mortality. A negative significant correlation was observed between PNI and NLR (r: -0.692), SII (r: -0.591), and CONUT (r: -0.511). Significant correlations were observed between CONUT and NLR (r: 0.402), SII (r: 0.312). Conclusions: PNI, CONUT and NRI were found as more accurate prognostic indicators of nutritional status in patients with ischemic stroke. NLR and SII may be important predictive markers in the course and prognosis of stroke.

Development and validation of a nomogram for predicting 28-day mortality in patients with ischemic stroke.

BACKGROUND/AIM: We aimed to construct a validated nomogram model for predicting short-term (28-day) ischemic stroke mortality among critically ill populations. MATERIALS AND METHODS: We collected raw data from the Medical Information Mart for Intensive Care IV database, a comprehensive repository renowned for its depth and breadth in critical care information. Subsequently, a rigorous analytical framework was employed, incorporating a 10-fold cross-validation procedure to ensure robustness and reliability. Leveraging advanced statistical methodologies, specifically the least absolute shrinkage and selection operator regression, variables pertinent to 28-day mortality in ischemic stroke were meticulously screened. Next, binary logistic regression was utilized to establish nomogram, then applied concordance index to evaluate discrimination of the prediction models. Predictive performance of the nomogram was assessed by integrated discrimination improvement (IDI) and net reclassification index (NRI). Additionally, we generated calibration curves to assess calibrating ability. Finally, we evaluated the nomogram's net clinical benefit using decision curve analysis (DCA), in comparison with scoring systems clinically applied under common conditions. RESULTS: A total of 2089 individuals were identified and assigned into training (n = 1443) or validation (n = 646) cohorts. Various identified risk factors, including age, ethnicity, marital status, underlying metastatic solid tumor, Charlson comorbidity index, heart rate, Glasgow coma scale, glucose concentrations, white blood cells, sodium concentrations, potassium concentrations, mechanical ventilation, use of heparin and mannitol, were associated with short-term (28-day) mortality in ischemic stroke individuals. A concordance index of 0.834 was obtained in the training dataset, indicating that our nomogram had good discriminating ability. Results of IDI and NRI in both cohorts proved that our nomogram had positive improvement of predictive performance, compared to other scoring systems. The actual and predicted incidence of mortality showed favorable concordance on calibration curves (P > 0.05). DCA curves revealed that, compared with scoring systems clinically used under common conditions, the constructed nomogram yielded a greater net clinical benefit. CONCLUSIONS: Utilizing a comprehensive array of fourteen readily accessible variables, a prognostic nomogram was meticulously formulated and rigorously validated to provide precise prognostication of short-term mortality within the ischemic stroke cohort.

Twenty-four-hour blood pressure trajectories and clinical outcomes in patients who had an acute ischaemic stroke.

OBJECTIVE: The management of blood pressure (BP) in acute ischaemic stroke remains a subject of controversy. This investigation aimed to explore the relationship between 24-hour BP patterns following ischaemic stroke and clinical outcomes. METHODS: A cohort of 4069 patients who had an acute ischaemic stroke from 26 hospitals was examined. Five systolic BP trajectories were identified by using latent mixture modelling: trajectory category 5 (190-170 mm Hg), trajectory category 4 (180-140 mm Hg), trajectory category 3 (170-160 mm Hg), trajectory category 2 (155-145 mm Hg) and trajectory category 1 (150-130 mm Hg). The primary outcome was a composite outcome of death and major disability at 3 months poststroke. RESULTS: Patients with trajectory category 5 exhibited the highest risk, while those with trajectory category 1 had the lowest risk of adverse outcomes at 3-month follow-up. Compared with the patients in the trajectory category 5, adjusted ORs (95% CIs) for the primary outcome were 0.79 (0.58 to 1.10), 0.70 (0.53 to 0.93), 0.64 (0.47 to 0.86) and 0.47 (0.33 to 0.66) among patients in trajectory category 4, trajectory category 3, trajectory category 2 and trajectory category 1, respectively. Similar trends were observed for death, vascular events and the composite outcome of death and vascular events. CONCLUSION: Patients with persistently high BP at 180 mm Hg within 24 hours of ischaemic stroke onset had the highest risk, while those maintaining stable BP at a moderate-low level (150 mm Hg) or even a low level (137 mm Hg) had more favourable outcomes.

The impact of pre-stroke metformin use on clinical outcomes after acute ischemic stroke: A systematic review and meta-analysis.

OBJECTIVES: Stroke is a leading cause of mortality and disability globally, with limited treatment options available for acute ischemic stroke (AIS) patients. Type 2 diabetes mellitus (T2DM) is not only widespread but also a known risk factor for stroke. Our meta-analysis aims to assess the influence of pre-stroke metformin use on the clinical outcomes in AIS patients with T2DM. MATERIALS AND METHODS: We conducted this study following PRISMA guidelines, searching the following databases: Medline, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials up to February 29, 2024. All studies providing separate data on AIS patients using metformin were included, and statistical analysis was conducted using R software to pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CI). RESULTS: Out of 1051 studies, 7 met the inclusion criteria for our meta-analysis with a total of 11589 diabetic patients, including 5445 patients taking metformin and 6144 diabetic patients in the non-metformin group. Compared to the non-metformin group, the metformin group had a significantly higher rate of mRS 0-2 score at discharge (OR 1.56; 95% CI 1.25:1.95; p=< 0.01) and a lower rate of 90-day mortality (OR 0.51; 95% CI 0.42:0.61; p=< 0.01), with no significant difference in sICH (OR 0.88; 95% CI 0.47:1.64; p= 0.68) between the two groups. CONCLUSIONS: Our meta-analysis demonstrated that pre-stroke metformin use is associated with higher functional independence and lower mortality in AIS patients with T2DM.

Lactate-to-albumin ratio: A promising predictor of 28-day all-cause mortality in critically Ill patients with acute ischemic stroke.

INTRODUCTION: Numerous diseases have been found to be associated with the lactate-to-albumin ratio (LAR), as confirmed by existing research. This study aims to investigate the relationship between LAR within 24 hours of admission and a 28-day mortality rate in patients manifesting ischemic stroke. METHODS: This retrospective cohort study utilized data from the Medical Information Mart for Intensive Care IV (MIMIC-IV, version 2.1) database. We included adult patients with acute ischemic stroke (AIS) who were admitted to the intensive care unit. The primary outcome entailed evaluating the ability of LAR to predict death at 28-day of hospital admission in patients with AIS. RESULTS: A total of 502 patients with ischemic stroke were enrolled in the study, of which 185 (36.9 %) died within 28 days after hospital admission. We identified a linear association between LAR and mortality risk. Compared with the reference group (first LAR tertile), the 28-day mortality was increased in the highest tertile; the fully adjusted HR value was 1.21 (1.08 to 1.40). the Area Under the Curve (AUC) value for LAR was 58.26 % (95 % CI: 53.05 % - 63.46 %), which was higher than that for arterial blood lactate (AUC = 56.88 %) and serum albumin (AUC = 55.29 %) alone. It was not inferior even when compared to SOFA (AUC = 56.28 %). The final subgroup analysis exhibited no significant interaction of LAR with each subgroup (P for interaction: 0.079 - 0.848). CONCLUSION: In our study, LAR emerged as a promising predictor of all-cause mortality in acute ischemic stroke patients within 28 days of admission.

Predictive value of glycoprotein DKK3 for early neurological deterioration after ischemic stroke.

OBJECTIVE: To explore the value of serum Dickkopf-3 (sDKK3) in predicting Early Neurological Deterioration (END) and in-hospital adverse outcomes in acute ischemic stroke (AIS) patients. METHODS: AIS patients (n = 200) were included and assessed by the National Institutes of Health Stroke Rating Scale. Serum Dkk3 levels were assessed by ELISA. END was defined as an increase of ≥ 4 points in NIHSS score within 72h. The biological threshold of sDKK3 level and END occurrence were predicted based on X-tile software. Primary outcomes were END and all-cause death, and the secondary outcome was ICU admission during hospitalization. The logistic regression model and Cox risk regression model were applied to evaluate the relationship between DKK3 level and END incidence, all-cause in-hospital mortality, and in-hospital adverse outcomes (ICU admission). RESULTS: During hospitalization, the incidence of END in patients with AIS was 13.0 %, and the mortality rate within 7 days after END was 11.54 % (3/26). In patients below the serum DKK3 cutoff (93.0 pg/mL), the incidence of END was 43.5 % (20/48). Patients with lower sDKK3 levels were associated with a 1.188-fold increased risk of developing END (OR = 1.188, 95 % CI 1.055‒1.369, p < 0.0001). However, there was no significant association with admission to the ICU. sDKK3 below the threshold (93.0 pg/mL) was a risk factor for death. CONCLUSION: Predictive threshold levels of serum DKK3 based on X-tile software may be a potential predictive biomarker of in-hospital END in patients with AIS, and low levels of DKK3 are independently associated with increased in-hospital mortality.

Prognosis of patients with coexisting obesity and malnutrition after ischemic stroke: A cohort study.

BACKGROUND: The double burden of malnutrition, defined as the coexistence of obesity and malnutrition, is an increasing global health concern and is unclear in patients after ischemic stroke. The current study explored the combined impacts of obesity and malnutrition on patients with ischemic stroke. METHODS: We conducted a single-center prospective cohort study with patients with ischemic stroke enrolled in Minhang Hospital in China between January 2018 and December 2022. Patients were stratified into four categories based on their obesity (defined by body mass index) and nutritional status (classified according to the Controlling Nutritional Status score): (1) nourished nonobese, (2) malnourished nonobese, (3) nourished obese, and (4) malnourished obese. The primary end points were poor outcomes and all-cause mortality at 3 months. RESULTS: A total of 3160 participants with ischemic stroke were included in our study, of which 64.7% were male and the mean age was 69 years. Over 50% of patients were malnourished. At 3-month follow-up, the malnourished nonobese had the worst outcomes (34.4%), followed by the malnourished obese (33.2%), nourished nonobese (25.1%), and nourished obese (21.8%; P < 0.001). In multivariable analyses, with nourished nonobese group as the reference, the malnourished nonobese group displayed poorer outcomes (odds ratio [OR], 1.395 [95% CI, 1.169-1.664], P < 0.001) and higher all-cause mortality (OR, 1.541 [95% CI, 1.054-2.253], P = 0.026), but only a nonsignificant increase in poor prognosis rate (33.2% vs. 25.1%, P = 0.102) and mortality (4.2% vs. 3.6%, P = 0.902) were observed in the malnourished obese group. CONCLUSION: A high prevalence of malnutrition is observed in the large population suffering from ischemic attack, even in the obese. Malnourished patients have the worst prognosis particularly in those with severe nutritional status regardless of obesity, while the best functional outcomes and the lowest mortality are demonstrated in nourished obese participants.

Autophagy-related 5 in acute ischemic stroke: Variation and linkage with neurofunction, and survival.

OBJECTIVE: Autophagy-related 5 (ATG5) facilitates the pathologic process of acute ischemic stroke (AIS) via multiple ways. This study aimed to identify the association of serum ATG5 with clinical outcomes in AIS patients. METHODS: Serum ATG5 from 280 AIS patients were detected at admission, Day (D)1, D3, D7, D30, and D90 after admission by enzyme-linked immunosorbent assay. The median (interquartile range) follow-up was 21.1 (5.9-43.9) months. Another 50 healthy controls (HCs) were also enrolled for serum ATG5 determination. RESULTS: ATG5 was elevated (p < 0.001) (vs. HCs), and positively correlated with hyperlipidemia (p = 0.016), and the national institutes of health stroke scale score (p = 0.001) in AIS patients. Interestingly, ATG5 was increased from admission to D1, but gradually decreased until D90 (p < 0.001). Besides, 85 (30.4%) and 195 (69.6%) AIS patients were assessed as modified Rankin Scale (mRS) >2 and mRS ≤2 at D90, respectively. ATG5 at admission, D1, D3, D30, and D90 was elevated in AIS patients with mRS >2 versus those with mRS ≤2 (all p < 0.050). ATG5 at admission, D1, D3, D7, D30, or D90 was elevated in relapsed (vs. non-relapsed) or died (vs. survived) AIS patients (all p < 0.050). Recurrence-free survival was shortened in AIS patients with high (≥52.0 ng/mL) ATG5 versus those with low (<52.0 ng/mL) ATG5 at admission, D3, D7, and D30 (all p < 0.050); overall survival was shorter in AIS patients with high (vs. low) ATG5 at D7 and D30 (both p < 0.050). INTERPRETATION: Serum ATG5 elevates at first, thereafter gradually declines, whose elevation associates with neurological dysfunction, recurrence, and death risk in AIS patients.

Study on the correlation between serum indole-3-propionic acid levels and the progression and prognosis of acute ischemic stroke.

OBJECTIVE: This study aimed to explore the correlation between the serum level of indole-3-propionic acid (IPA) and the progression and prognosis of acute cerebral infarction (ACI). METHODS: This study enrolled 197 patients with ACI, and 53 participants from a community-based stroke screening program during the same period were included as the control group. The patients with ACI were divided into quartiles of serum IPA. A logistic regression model was used for comparison. Receiver operating characteristic (ROC) curves were drawn to evaluate the predictive value of the IPA. RESULTS: Compared with the healthy control group, the ACI group had lower serum IPA (P < 0.05). The serum IPA was an independent factor for acute ischemic stroke (OR=0.992, 95% CI: 0.984-0.999, P=0.035). The serum IPA was lower in patients with progressive stroke or poor prognosis than in patients with stable stroke or good prognosis (P < 0.05). Patients with ACI with low serum IPA are prone to progression and poor prognosis. The best cutoff value for predicting progression was 193.62 pg/mL (sensitivity, 67.5%; specificity 83.7%), and that for poor prognosis was 193.77 pg/mL (sensitivity, 71.1%; specificity, 72.5%). CONCLUSION: The serum level of IPA was an independent predictor of ACI and had certain clinical value for predicting stroke progression and prognosis in patients with ACI.

Tenecteplase for Stroke at 4.5 to 24 Hours with Perfusion-Imaging Selection.

BACKGROUND: Thrombolytic agents, including tenecteplase, are generally used within 4.5 hours after the onset of stroke symptoms. Information on whether tenecteplase confers benefit beyond 4.5 hours is limited. METHODS: We conducted a multicenter, double-blind, randomized, placebo-controlled trial involving patients with ischemic stroke to compare tenecteplase (0.25 mg per kilogram of body weight, up to 25 mg) with placebo administered 4.5 to 24 hours after the time that the patient was last known to be well. Patients had to have evidence of occlusion of the middle cerebral artery or internal carotid artery and salvageable tissue as determined on perfusion imaging. The primary outcome was the ordinal score on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability and a score of 6 indicating death) at day 90. Safety outcomes included death and symptomatic intracranial hemorrhage. RESULTS: The trial enrolled 458 patients, 77.3% of whom subsequently underwent thrombectomy; 228 patients were assigned to receive tenecteplase, and 230 to receive placebo. The median time between the time the patient was last known to be well and randomization was approximately 12 hours in the tenecteplase group and approximately 13 hours in the placebo group. The median score on the modified Rankin scale at 90 days was 3 in each group. The adjusted common odds ratio for the distribution of scores on the modified Rankin scale at 90 days for tenecteplase as compared with placebo was 1.13 (95% confidence interval, 0.82 to 1.57; P = 0.45). In the safety population, mortality at 90 days was 19.7% in the tenecteplase group and 18.2% in the placebo group, and the incidence of symptomatic intracranial hemorrhage was 3.2% and 2.3%, respectively. CONCLUSIONS: Tenecteplase therapy that was initiated 4.5 to 24 hours after stroke onset in patients with occlusions of the middle cerebral artery or internal carotid artery, most of whom had undergone endovascular thrombectomy, did not result in better clinical outcomes than those with placebo. The incidence of symptomatic intracerebral hemorrhage was similar in the two groups. (Funded by Genentech; TIMELESS ClinicalTrials.gov number, NCT03785678.).

Differential impacts of admission LDL-cholesterol on early vascular outcomes by ischemic stroke subtypes.

BACKGROUND: Because ischemic stroke is heterogeneous, the associations between low-density lipoprotein (LDL)-cholesterol levels and early vascular outcomes might be different according to the stroke subtype in acute ischemic stroke patients. METHODS: This study was an analysis of a prospective, multicenter, stroke registry. Acute ischemic stroke patients previously not treated with statins were included. Admission LDL-cholesterol levels were divided into 7 groups at 20 mg/dl intervals for comparison. The primary early vascular outcome was a composite of stroke, myocardial infarction (MI) and all-cause mortality within 3 months. RESULTS: A total of 38,531 patients (age, 68.5 ± 12.8 yrs; male, 59.6%) were analyzed for this study. The 3-month cumulative incidences of the composite of stroke, MI, and all-cause mortality significantly differed among the LDL-cholesterol level groups, with the highest event rate (11.11%) in the lowest LDL-cholesterol group (<70 mg/dl). After adjustment, the U-shaped associations of LDL-cholesterol levels with primary outcome and all-cause mortality were observed. For the stroke subtypes, there were substantial interactions between the LDL-cholesterol groups and stroke subtype and all-cause mortality (Pinteraction=0.07). Different patterns, with higher risks of all-cause mortality in the lower LDL-cholesterol in the large artery atherosclerosis subtype (adjusted hazard ratio [aHR] 1.29, 95% confidence interval [CI] 0.98-1.69), but in the higher LDL-cholesterol in the cardioembolism subtype (aHR 1.71 95% CI [1.28-2.29]), were observed among stroke subtypes. CONCLUSION: We found that there were differential associations of admission LDL-cholesterol levels with all-cause mortality within 3 months among stroke subtypes. These results suggest that admission LDL-cholesterol and early vascular outcomes had complex relationships in patients with ischemic stroke according to the stroke subtypes.

Extracranial-Intracranial Bypass and Risk of Stroke and Death in Patients With Symptomatic Artery Occlusion: The CMOSS Randomized Clinical Trial.

Importance: Prior trials of extracranial-intracranial (EC-IC) bypass surgery showed no benefit for stroke prevention in patients with atherosclerotic occlusion of the internal carotid artery (ICA) or middle cerebral artery (MCA), but there have been subsequent improvements in surgical techniques and patient selection. Objective: To evaluate EC-IC bypass surgery in symptomatic patients with atherosclerotic occlusion of the ICA or MCA, using refined patient and operator selection. Design, Setting, and Participants: This was a randomized, open-label, outcome assessor-blinded trial conducted at 13 centers in China. A total of 324 patients with ICA or MCA occlusion with transient ischemic attack or nondisabling ischemic stroke attributed to hemodynamic insufficiency based on computed tomography perfusion imaging were recruited between June 2013 and March 2018 (final follow-up: March 18, 2020). Interventions: EC-IC bypass surgery plus medical therapy (surgical group; n = 161) or medical therapy alone (medical group; n = 163). Medical therapy included antiplatelet therapy and stroke risk factor control. Main Outcomes and Measures: The primary outcome was a composite of stroke or death within 30 days or ipsilateral ischemic stroke beyond 30 days through 2 years after randomization. There were 9 secondary outcomes, including any stroke or death within 2 years and fatal stroke within 2 years. Results: Among 330 patients who were enrolled, 324 patients were confirmed eligible (median age, 52.7 years; 257 men [79.3%]) and 309 (95.4%) completed the trial. For the surgical group vs medical group, no significant difference was found for the composite primary outcome (8.6% [13/151] vs 12.3% [19/155]; incidence difference, -3.6% [95% CI, -10.1% to 2.9%]; hazard ratio [HR], 0.71 [95% CI, 0.33-1.54]; P = .39). The 30-day risk of stroke or death was 6.2% (10/161) in the surgical group and 1.8% (3/163) in the medical group, and the risk of ipsilateral ischemic stroke beyond 30 days through 2 years was 2.0% (3/151) and 10.3% (16/155), respectively. Of the 9 prespecified secondary end points, none showed a significant difference including any stroke or death within 2 years (9.9% [15/152] vs 15.3% [24/157]; incidence difference, -5.4% [95% CI, -12.5% to 1.7%]; HR, 0.69 [95% CI, 0.34-1.39]; P = .30) and fatal stroke within 2 years (2.0% [3/150] vs 0% [0/153]; incidence difference, 1.9% [95% CI, -0.2% to 4.0%]; P = .08). Conclusions and Relevance: Among patients with symptomatic ICA or MCA occlusion and hemodynamic insufficiency, the addition of bypass surgery to medical therapy did not significantly change the risk of the composite outcome of stroke or death within 30 days or ipsilateral ischemic stroke beyond 30 days through 2 years. Trial Registration: ClinicalTrials.gov Identifier: NCT01758614.

Recent Vitamin K Antagonist Use and Intracranial Hemorrhage After Endovascular Thrombectomy for Acute Ischemic Stroke.

Importance: Use of oral vitamin K antagonists (VKAs) may place patients undergoing endovascular thrombectomy (EVT) for acute ischemic stroke caused by large vessel occlusion at increased risk of complications. Objective: To determine the association between recent use of a VKA and outcomes among patients selected to undergo EVT in clinical practice. Design, Setting, and Participants: Retrospective, observational cohort study based on the American Heart Association's Get With the Guidelines-Stroke Program between October 2015 and March 2020. From 594 participating hospitals in the US, 32 715 patients with acute ischemic stroke selected to undergo EVT within 6 hours of time last known to be well were included. Exposure: VKA use within the 7 days prior to hospital arrival. Main Outcome and Measures: The primary end point was symptomatic intracranial hemorrhage (sICH). Secondary end points included life-threatening systemic hemorrhage, another serious complication, any complications of reperfusion therapy, in-hospital mortality, and in-hospital mortality or discharge to hospice. Results: Of 32 715 patients (median age, 72 years; 50.7% female), 3087 (9.4%) had used a VKA (median international normalized ratio [INR], 1.5 [IQR, 1.2-1.9]) and 29 628 had not used a VKA prior to hospital presentation. Overall, prior VKA use was not significantly associated with an increased risk of sICH (211/3087 patients [6.8%] taking a VKA compared with 1904/29 628 patients [6.4%] not taking a VKA; adjusted odds ratio [OR], 1.12 [95% CI, 0.94-1.35]; adjusted risk difference, 0.69% [95% CI, -0.39% to 1.77%]). Among 830 patients taking a VKA with an INR greater than 1.7, sICH risk was significantly higher than in those not taking a VKA (8.3% vs 6.4%; adjusted OR, 1.88 [95% CI, 1.33-2.65]; adjusted risk difference, 4.03% [95% CI, 1.53%-6.53%]), while those with an INR of 1.7 or lower (n = 1585) had no significant difference in the risk of sICH (6.7% vs 6.4%; adjusted OR, 1.24 [95% CI, 0.87-1.76]; adjusted risk difference, 1.13% [95% CI, -0.79% to 3.04%]). Of 5 prespecified secondary end points, none showed a significant difference across VKA-exposed vs VKA-unexposed groups. Conclusions and Relevance: Among patients with acute ischemic stroke selected to receive EVT, VKA use within the preceding 7 days was not associated with a significantly increased risk of sICH overall. However, recent VKA use with a presenting INR greater than 1.7 was associated with a significantly increased risk of sICH compared with no use of anticoagulants.

Prognostic performance of serum YKL-40 for one-year clinical outcomes in acute ischemic stroke.

BACKGROUND: Effects of YKL-40 on one-year clinical outcomes including poor clinical outcome, all-cause mortality, and stroke recurrence among acute ischemic stroke (AIS) patients remained elusive. The purpose of this study was to explore the association between serum YKL-40 at admission and one-year clinical outcomes in AIS patients. METHODS: In this prospective cohort study, a total of 1002 participants out of 1361 AIS patients from two centers were included for current analysis. Serum YKL-40 concentrations were measured via enzyme-linked immunosorbent assay. Multivariable logistic or Cox regression were performed to explore the independent association of YKL-40 with one-year clinical outcomes, including poor outcome (modified Rankin Scale of 3-6), all-cause mortality, and recurrent stroke. C-statistic, net reclassification index (NRI) and integrated discrimination improvement (IDI) were calculated to evaluate the discriminatory and predictive power of YKL-40 when added to conventional model. RESULTS: Compared with the first quartile of YKL-40, the adjusted odds ratios or hazard ratios with 95% confidence intervals of the fourth quartile were 3.032 (1.627-5.650) for poor outcome, 2.886 (1.320-6.308) for all-cause mortality and 1.694 (0.906-3.169) for recurrent stroke. The addition of serum YKL-40 to conventional model significantly improved reclassification for poor outcome (NRI 0.053, P = 0.031; IDI 0.018, P = 0.001) and all-cause mortality (NRI 0.162, P = 0.036). CONCLUSIONS: Elevated serum YKL-40 at admission might be independently associated with one-year poor outcome and all-cause mortality but not stroke recurrence among Chinese AIS patients.

Safety outcomes of early initiation of antithrombotic agents within 24 h after intravenous alteplase at 0.6 mg/kg.

BACKGROUND: We examined outcome of acute ischemic stroke (AIS) with administration of antithrombotics within 24 h after intravenous low-dose alteplase. METHODS: Consecutive AIS patients who were treated with intravenous alteplase at 0.6 mg/kg from 2005 to 2021 were retrospectively included in our single-center registry. Patients were classified into two groups: those who received antithrombotics within 24 h after intravenous alteplase (early initiation group) and those who did not (control group). Safety outcomes were any intracranial hemorrhage (ICH), symptomatic ICH (sICH) within 36 h after onset, and death within 3 months. sICH was defined as any ICH with a ≥ 4-point increase in the National Institutes of Health Stroke Scale (NIHSS) score or death within 36 h. RESULTS: Of 1111 patients (women, 426; median age, 76 [interquartile range, 69-83] years; median NIHSS score, 11 [6-19]; cardioembolism, 580 [52.2%]), early initiation group comprised 58 patients (22; 72 [65-80] years; 7 [4-12]; 11 [19.0%]) and control group comprised 1053 patients (404; 77 [69-84] years; 11 [6-19]; 569 [54.1%]). No significant between-group differences were observed in the incidence of any ICH (17.2% vs. 21.6%; adjusted odds ratio [aOR], 1.18; 95% confidence interval [CI], 0.57-2.44), sICH (0% vs. 0.9%, P = 1.00), or death within 3 months (5.2% vs. 6.7%; aOR, 1.23; 95% CI, 0.36-4.23). CONCLUSIONS: Early initiation of antithrombotics after intravenous alteplase at 0.6 mg/kg did not increase the rate of sICH or death within 3 months and may be used with caution in patients with advanced neurological deterioration.