Impact of stress hyperglycemia on outcomes in patients with large ischemic stroke.

BACKGROUND: Clinical evidence of the potential influence of stress hyperglycemia ratio (SHR) for patients with large ischemic stroke whether or not receiving endovascular therapy is not clear. METHODS: This study was a subanalysis of a prospective, multicenter registry, and included 745 patients with large ischemic stroke across 38 centers in China. A total of 427 patients were included in this study, with 285 received endovascular therapy (EVT) and 142 received standard medical therapy (SMT). SHR was defined as glucose (mmol/L)/(1.59 × HbA1C)-2.59. The primary outcome was a moderate neurological outcome (modified Rankin Scale (mRS) score ≤3) at 90 days. RESULTS: A significant interaction was observed between SHR and whether received EVT (p=0.017). Among patients who received EVT (adjusted OR (aOR) 0.46; 95% CI 0.23 to 0.92; p=0.029), patients in the highest tertile of SHR were significantly less likely to achieve a moderate neurological outcome at 90 days compared with those in the lowest tertile. However, this association was not observed in patients receiving SMT (aOR 2.46; 95% CI 0.74 to 8.21; p=0.142). EVT patients with higher SHR had a significantly higher incidence of symptomatic intracranial hemorrhage compared with lower SHR (aOR 3.29; 95% CI 1.08 to 10.06; p=0.036), while such an association was not observed in the SMT group (aOR 1.52; 95% CI 0.56 to 4.12; p=0.410). CONCLUSIONS: In patients with large ischemic stroke treated with EVT, SHR is associated with a reduced likelihood of achieving a moderate neurological outcome, as well as an increased risk of symptomatic intracranial hemorrhage. TRIAL REGISTRATION NUMBER: ChiCTR2100051664.

Adjunctive intra-arterial tenecteplase after successful endovascular thrombectomy in patients with large vessel occlusion stroke (POST-TNK): Study rationale and design.

RATIONALE: Adjunct intra-arterial alteplase has been shown to potentially improve clinical outcomes in patients with large vessel occlusion (LVO) stroke who have undergone successful endovascular thrombectomy. Tenecteplase, known for its enhanced fibrin specificity and extended activity duration, could potentially enhance outcomes in stroke patients after successful reperfusion when used as an adjunct intra-arterial therapy. AIM: To explore the safety and efficacy of intra-arterial tenecteplase after successful endovascular thrombectomy in patients with LVO stroke. SAMPLE SIZE: To randomize 498 participants 1:1 to receive intra-arterial tenecteplase or no intra-arterial adjunctive thrombolysis therapy. METHODS AND DESIGN: An investigator-initiated, prospective, randomized, open-label, blind-endpoint multicenter clinical trial. Eligible patients with anterior circulation LVO stroke presenting within 24 h from symptom onset (time last known well) and excellent to complete reperfusion (expanded Thrombolysis In Cerebral Infarction (eTICI) scale 2c-3) at endovascular thrombectomy are planned to be randomized. OUTCOMES: The primary outcome is freedom from disability (modified Rankin Scale, mRS, of 0-1) at 90 days. The primary safety outcomes are mortality through 90 days and symptomatic intracranial hemorrhage within 48 h. DISCUSSION: The POST-TNK trial will evaluate the efficacy and safety of intra-arterial tenecteplase in patients with LVO stroke and excellent to complete reperfusion.

Development of predictive model for post-stroke depression at discharge based on decision tree algorithm: A multi-center hospital-based cohort study.

OBJECTIVE: Post-stroke depression (PSD) is one of the most common and severe neuropsychological sequelae after stroke. Using a prediction model composed of multiple predictors may be more beneficial than verifying the predictive performance of any single predictor. The primary objective of this study was to construct practical prediction tools for PSD at discharge utilizing a decision tree (DT) algorithm. METHODS: A multi-center prospective cohort study was conducted from May 2018 to October 2019 and stroke patients within seven days of onset were consecutively recruited. The independent predictors of PSD at discharge were identified through multivariate logistic regression with backward elimination. Classification and regression tree (CART) algorithm was employed as the DT model's splitting method. RESULTS: A total of 876 stroke patients who were discharged from the neurology departments of three large general Class A tertiary hospitals in Wuhan were eligible for analysis. Firstly, we divided these 876 patients into PSD and non-PSD groups, history of coronary heart disease (OR = 1.835; 95 % CI, 1.106-3.046; P = 0.019), length of hospital stay (OR = 1.040; 95 % CI, 1.013-1.069; P = 0.001), NIHSS score (OR = 1.124; 95 % CI, 1.052-1.201; P = 0.001), and Mini mental state examination (MMSE) score (OR = 0.935; 95 % CI, 0.893-0.978; P = 0.004) were significant predictors. The subgroup analysis results have shown that hemorrhagic stroke, history of hypertension and higher modified Rankin Scale score (mRS) score were associated with PSD at discharge in the young adult stroke patients. CONCLUSIONS: Several predictors of PSD at discharge were identified and convenient DT models were constructed to facilitate clinical decision-making.

Bridging therapy versus direct endovascular thrombectomy in patients with established large infarct: a prospective cohort study.

BACKGROUND: Whether patients with large core infarctions should undergo intravenous thrombolysis (IVT) before endovascular thrombectomy (EVT) is currently a subject of controversy. The study aimed to investigate the association of prior use of IVT with outcomes of EVT patients with large core infarctions. MATERIALS AND METHODS: This prospective cohort included patients with acute large vessel occlusion and Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of 0-5 from 38 stroke centers across China between November 2021 and February 2023. The primary outcome was defined as favorable functional outcomes, which is 90-day modified Rankin Scale (mRS) scores ranging from 0 to 3. Procedural outcomes included measures of successful and effective recanalization. Safety outcomes included the incidence of any intracranial hemorrhage (ICH), symptomatic ICH, and 90-day mortality. RESULTS: Of 490 patients, 122 (24.5%) were treated with IVT before EVT. Bridging therapy and its transfer modes showed no association with any of the measured outcomes. Compared to direct EVT, bridging therapy was associated with a decreased risk of symptomatic ICH in very elderly patients and a decreased risk of any ICH in patients with admission NIHSS scores of 20 or higher. Additionally, early stroke severity may alter the odds of any ICH in patients with bridging therapy versus direct EVT (inverse probability weighting adjusted P value for interaction=0.003 and 0.007, respectively). CONCLUSION: In large core infarction patients with high admission NIHSS or very elderly age, bridging therapy appears to have some advantages over direct EVT in reducing the risk of ICH.

Left Atrial Strain for Prediction of Left Ventricular Reverse Remodeling After ST-segment Elevation Myocardial Infarction by Cardiac Magnetic Resonance Feature Tracking.

PURPOSE: The study aimed to investigate the potential utility of left atrial (LA) strain by using cardiac magnetic resonance feature-tracking (CMR-FT) to predict left ventricular reverse remodeling (LVRR) following ST-segment elevation myocardial infarction (STEMI). MATERIALS AND METHODS: Patients with a first STEMI treated by primary percutaneous coronary intervention were consecutively enrolled in the prospective study and underwent CMR scans at 5 days and 4 months. LA global longitudinal strain (reservoir strain [εs], conduit strain [εe], booster strain [εa]) and corresponding strain rate were assessed by CMR-FT using cine images. LVRR was defined as a reduction in the LV end-systolic volume index of >10% from baseline to follow-up. Logistic regression analyses were performed to determine the predictors of LVRR. RESULTS: Of 90 patients analyzed, patients with LVRR (n=35, 39%) showed higher values of LA strain and strain rate and less extensive infarct size (IS) compared with patients without LVRR (n=55, 61%) at initial and second CMR. The LVRR group demonstrated significant improvements in LV and LA cardiac function over time, especially the obvious increase in LA strain and strain rate. In multivariate logistic regression analyses, εs and εe, together with IS, were independent predictors of LVRR. The combination of εs and IS could optimally predict the LVRR with the highest area under the curve of 0.743. CONCLUSIONS: Post-STEMI patients with LVRR presented better recovery from cardiac function and LA deformation compared with patients without LVRR. Assessment of εs and εe by using CMR-FT after STEMI enabled prediction of LVRR.

A fault isolation strategy for industrial processes using outlier-degree-based variable contributions.

In industrial process monitoring, it is always a challenging and practical problem to analyze the causes of the system fault by isolating true fault variables from vast amounts of process data. However, the phenomenon of smearing effect occurs by using the traditional contribution analysis-based isolation methods since the defined isolation indices of different variables affect each other. In this paper, a new fault isolation method is proposed based on local outlier factor and improved k-nearest neighbor rule aiming to improve the isolation accuracy. Firstly, the nearest neighbors of each sample are obtained along the direction of a specific variable. Based on the nearest neighbors, the outlier-degree value of the variable is calculated and regarded as the contribution of the variable. Then, the contribution of the variable in all samples are obtained in the same way, among which the maximum one is selected as the isolation threshold value of this variable. During the online monitoring, the contribution of the variable in the newly collected sample is calculated in real time. Once the contribution is greater than the threshold, the variable is judged to be the dominant factor causing the system fault. Two cases on numerical example and Tennessee Eastman process are conducted to evaluate the effectiveness of the proposed method.

Exploring the potential molecular intersection of stroke and major depression disorder.

Stroke and major depression disorder are common neurological diseases, and a large number of clinical studies have shown that there is a close relationship between the two diseases, but whether the two diseases are linked at the genetic level needs to be further explored. The purpose of this study was to explore the comorbidity mechanism of stroke and major depression by using bioinformatics technology and animal experiments. From the GEO database, we gathered transcriptome data of stroke and depression mice (GSE104036, GSE131712, GSE81672, and GSE146845) and identified comorbid gene set through edgR and WGCNA analyses. Further analysis revealed that these genes were enriched in pathways associated with cell death. Programmed cell death gene sets (PCDGs) are generated from genes related to apoptosis, necroptosis, pyroptosis and autophagy. The intersection of PCDGs and comorbid gene set resulted in two hub genes, Mlkl and Nlrp3. Single-cell sequencing analysis indicated that Mlkl and Nlrp3 are mainly influential on endothelial cells and microglia, suggesting that the impairment of these two cell types may be a factor in the relationship between stroke and major depression. This was experimentally confirmed by RT-PCR and immunofluorescence staining. Our research revealed that two specific genes, namely, Mlkl and Nlrp3, play crucial roles in the complex mechanism that links stroke and major depression. Additionally, we have predicted six possible therapeutic agents and the outcomes of docking simulations of target proteins and drug molecules.

Peripheral inflammation and trajectories of depressive symptomology after ischemic stroke: A prospective cohort study.

BACKGROUND: Understanding the association of peripheral inflammation and post-stroke depressive symptomology (PSDS) might provide further insights into the complex etiological mechanism of organic depression. However, studies focusing on the longitudinal patterns of PSDS were limited and it remained unclear whether peripheral inflammation influences the occurrence and development of PSDS. METHODS: A total of 427 prospectively enrolled and followed ischemic stroke patients were included in the analytical sample. Depressive symptomology was assessed on four occasions during 1 year after ischemic stroke. Peripheral inflammatory proteins on admission and repeated measures of peripheral immune markers in three stages were collected. Latent class growth analysis (LCGA) was employed to delineate group-based trajectories of peripheral immune markers and PSDS. Multinomial regression was performed to investigate the association of peripheral inflammation with PSDS trajectories. RESULTS: Four distinct trajectories of PSDS were identified: stable-low (n = 237, 55.5 %), high-remitting (n = 120, 28.1 %), late-onset (n = 44, 10.3 %), and high-persistent (n = 26, 6.1 %) PSDS trajectories. The elevation of peripheral fibrinogen on admission increased the risk of high-persistent PSDS in patients with early high PSDS. Additionally, chronic elevation of innate immune levels might not only increase the risk of high-persistent PSDS in patients with early high PSDS but also increase the risk of late-onset PSDS in patients without early high PSDS. The elevation of adaptive immune levels in the convalescence of ischemic stroke may contribute to the remission of early high PSDS. CONCLUSIONS: Peripheral immunity could influence the development of PSDS, and this influence might have temporal heterogeneity. These results might provide vital clues for the inflammation hypothesis of PSD.

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.

The Association Between National Institutes of Health Stroke Scale Score and Clinical Outcome in Patients with Large Core Infarctions Undergoing Endovascular Treatment.

INTRODUCTION: This study aimed to analyze the association between baseline National Institutes of Health Stroke Scale (NIHSS) scores and clinical outcomes in patients with large core infarctions undergoing endovascular treatment (EVT), a relationship that remains unclear. METHODS: Data were obtained from the MAGIC study, a prospective multicenter cohort study focusing on patients with acute large core ischemic stroke. This analysis evaluated the impact of NIHSS scores on EVT outcomes in patients with large core infarctions. Primary outcome metrics included favorable outcomes (modified Rankin Scale [mRS] of 0-3 at 90 days), while secondary outcomes encompassed shifts in mRS scores, functional independence (mRS score of 0-2), mRS score of 0-4, and successful recanalization rates. Adverse events considered were symptomatic intracranial hemorrhage (sICH) and mortality. RESULTS: A total of 490 patients were enrolled in this study. Higher baseline NIHSS scores were inversely correlated with favorable outcomes (adjusted odds ratio [OR] in model 3, 0.848 [0.797-0.903], P < 0.001), particularly in patients with NIHSS scores above 20 (adjusted OR in model 3, 0.518 [0.306-0.878] vs. 0.290 [0.161-0.523]). Regarding adverse events, higher baseline NIHSS scores significantly correlated with increased 90-day mortality rates (adjusted OR in model 3, 1.129 [1.072-1.189], P < 0.001). This correlation became insignificant when baseline NIHSS scores exceeded 22. Additionally, baseline NIHSS scores partially mediated the association between age (indirect effect = - 0.0005, 19.39% mediated) and sex (indirect effect = 0.0457, 25.08% mediated) with the primary outcome. CONCLUSIONS: The findings indicate that higher baseline NIHSS scores correlate with poorer outcomes and increased mortality, particularly when scores exceed 20. Moreover, age and sex indirectly influence favorable outcomes through their association with baseline NIHSS scores.