Welcome to the WSC 2022 Interactive Program

Background and Aims

Objectives: The objective of this study is to evaluate the use of inpatient stroke flow process in adult patients’ length of stay who developed stroke whilst hospitalized. Time frame was from November 2019 till October 2021.

Background: Hospitalized adult patients are at high risk of developing stroke. Inpatient stroke flow processes is an effective practice as the stroke code that is being activated will fasten the process and initiate the stroke team which helps to prevent complications related to delayed stroke identification ,management thus length of stay .

Methods

Retrospective study was done using the data collected quarterly for inpatient adults’ clients who developed stroke while hospitalized length of stay resulted from lack of process. Audit over a period of two year from November 2019 till December 2021 was done These quantitative data was used to evaluate the improvement in inpatients adult that developed stroke while hospitalized through monitoring the length of stay.

Results

Decrease in length of stay noted in adult patients who developed stroke while hospitalized after inpatient stroke workflow was introduced from 25% in November 2019 to 0% in October 2021.

Conclusions

Inpatient stroke work flow is implemented in adult inpatients to improve patients’ safety. The structured process provided to the whole multidisciplinary team showed great improvement in practice. Evidences’ showed that having organized process for inpatients stroke improved clinical and process-based outcomes therefore length of stay as stroke is time window disease(3).Future studies are needed to measure if this process might be implemented in intensive care units as well.

Background and Aims

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common genetic disease among hereditary stroke diseases and is caused by a mutation in the NOTCH3 gene. Blood biomarkers related to Notch signaling pathway have not been investigated extensively in CADASIL. In this study, we measured the serum and plasma levels of NOTCH3 extracellular domain (N3ECD) and Jagged-1.

Methods

The study population consisted of 279 healthy participants, who visited the hospital for routine health check-up. At the time of the check-up, the information were collected from the participants. In this study, people with hypertension, diabetes mellitus, history of stroke or ischemic heart disease were excluded.

N3ECD and Jagged-1 protein levels were determined in serum and plasma samples by sandwich enzyme-linked immunosorbent assay (ELISA).

Results

The levels of N3ECD and Jagged-1 showed strong correlations in both serum (p<0.0001, r=0.2681) and plasma (p<0.0001, r=0.4065). The N3ECD levels were significantly higher in the serum than in plasma and tend to increase with age. In contrast, Jagged-1 levels had no difference between the serum and plasma levels and decreased with age.

Conclusions

This is the first study to measure N3ECD and Jagged-1 protein levels in healthy human serum and plasma. Taken together, our findings provide the basis for further studies investigating the clinical use of N3ECD and Jagged-1 for CADASIL and other Notch signaling-related diseases.

Background and Aims

Background: There is growing interest to use a new biomarker such as glycated albumin (GA). Contrast to glycated hemoglobin (HbA1c), GA showed inverse correlation with prestroke obesity status, but data are limited in ischemic stroke (IS).

Aims: We explored the associations between GA and body mass index (BMI) and investigated the inflammatory cytokines to support the academic background.

Methods

Methods: A total of 165 patients with hyperacute IS between 2011 and 2019 were included. To identify the association between GA and BMI, patients were divided into four groups according to the BMI quartiles. Inflammatory cytokines including (IL-1β, IL-10, IL-6, TNF-α and TNF-R1 were determined by ELISA kit using a ProcartaPlex multiplex immunoassay.

Results

Results: Among a total of included patients, the mean age was 68 years, and 67% were male.

The lowest BMI group had higher GA levels (GA 2T and 3T =80%) (p-value=0.017) and these U-shaped associations were maintained only in SVO etiology (p-value= 0.004). Plasma levels of IL-10 was positively correlated with BMI and showed U-shaped patten (p-value= 0.001).

Conclusions

Conclusions: The GA level and BMI had U-shaped associations in hyperacute IS. IL-10 acting as a protective cytokine for cardiovascular disease might be a novel role for this association. Although the GA is emerging favorable clinical marker for cardiovascular outcomes, obesity status should be considered to interpret those associations.

Background and Aims

To assess if a radiomic signature can provide incremental value to carotid high resolution magnetic resonance (HR-MR) imaging-based ‘vulnerable plaque’ features for improved risk profiling of culprit (clinically symptomatic) and non-culprit (clinically asymptomatic) carotid atheroma.

Methods

Fifty-five patients with previous transient ischaemic attack (TIA) or stroke had carotid HR-MR imaging within 2 weeks of the event were assessed. Imaging data was provided by the CARE-II multi-centre carotid imaging trial (ClinicalTrials.gov Identifier: NCT02017756). The classification power of radiomics in identifying the culprit carotid atheroma was assessed by implementing machine learning in a binary classifier model. Robustness of these features was investigated across image quantisation settings to assess repeatability and reproducibility of results.

Results

Radiomics combined with conventional biomarkers such as morphological features and stenosis measurement provides incremental value over a the conventional biomarkers in themselves (area under curve (AUC) = 0.819 ± 0.002 and 0.689 ± 0.019 respectively, p < 0.05). The predictive power of models combining radiomics, stenosis, and plaque types was higher than any of these methods alone. It was found that the T2w imaging-based radiomic features had consistently higher robustness and classification power compared with T1w. Features within the Grey Level Co-occurrence Matrix (GLCM), Grey Level Dependence Matrix (GLDM) and (Grey Level Size Zone Matrix (GLSZM) sub-types may be particularly useful in identifying textures which could identify vulnerable carotid plaques, in combination with calcification and IPH, which are identifiable using hrMRI.

Conclusions

Radiomics combined with HR-MR identifiable plaque-based models provide incremental value over traditional stenosis-based assessments of carotid lesion vulnerability.

Background and Aims

Background: Cardio-embolic strokes have poorer outcome and higher recurrence rate, compared to other varieties of ischemic stroke. A suitable diagnostic biomarker is crucial, as most cases remain elusive to standard investigations.

Aims: To determine the role of NT-pro BNP as a diagnostic biomarker for cardio-embolic stroke, and obtain a cut-off value in this regard.

Methods

50 patients of acute ischemic stroke presenting within 72 hours of symptom onset, were subjected to detailed history regarding risk-factors. Serum NT-Pro BNP levels were measured at presentation. Stroke etiology was ascertained by MRI Brain with angiography, carotid doppler, echocardiography and 48 hour Holter monitoring.

Results

Among the 50 patients of acute ischemic stroke (mean age 56.46 ± 15.9 years, M:F 3:2), 52% were of cardio-embolic etiology. At presentation, median (IQR) NT-Pro BNP level was significantly higher in cardio-embolic stroke [637.5(290-650) pg/ml], compared to non-cardio-embolic stroke [100(100-100) pg/ml] (p <.0001). Additionally, fasting blood sugar levels emerged as a significant independent predictor of cardio-embolic stroke. (p=0.003) On ROC analysis, the diagnostic performance of NT-Pro BNP level (area under the curve), optimum cut-off point and its sensitivity and specificity were 0.962 (95% CI: 0.865 to 0.996), 100 pg/ml, 92.31% and 100% respectively.

Conclusions

Serum NT-Pro BNP concentration is a useful biomarker for differentiating cardio-embolic stroke from other subtypes of acute ischemic stroke. Its use would aid the diagnosis of such strokes in a cost-effective manner, and facilitate timely anti-coagulant therapy for secondary prophylaxis.

Background and Aims

Evidence about whether miR-491-5p, miR-206, miR-21-5p or miR-3123 is associated with intermittent and functional outcomes after acute ischemic stroke (AIS) is scant. We aim to explore the relationship between these four microRNAs and functional outcomes as well as spontaneous hemorrhagic transformation (HT) after AIS.

Methods

We prospectively included AIS patients, collected blood samples within 72h after onset and assayed for miR-21-5p, miR-206, miR-3123 and miR-491-5p. MiRNAs expression was measured by quantitative real-time polymerase chain reaction and log-transformed. Unfavorable functional outcome was defined as modified Rankin Scale score≥ 3. Spontaneous HT referred to hemorrhage at ischemic site detected by follow-up imaging but not by admission imaging, without reperfusion therapies usage. Logistic regression, generalized additive model and 2-piecewise regression model were used to explore the independent, dose-dependent relationship between miRNAs expression and outcomes.

Results

We included 215 patients (66.7 ± 14.5 years; Female 38.6%). Lower expression of miR-491-5p significantly increased the risk of unfavorable functional outcomes at 3 months (OR 0.81 [95% CI, 0.66–0.98], P=0.037) and 1 year (OR 0.76 [95% CI, 0.61–0.94], P=0.011). Higher expression of miR-206 significantly increased the risk of spontaneous HT (OR 1.64, 95%CI 1.17–2.30, P= 0.004). Nonlinear, dose-dependent manners were found with inflection points of 2.103(miR-491-5p and 3-month outcome), 2.180(miR-491-5p and 1-year outcome) and 2.037(miR-206 and spontaneous HT), respectively.

Conclusions

Lower miR-491-5p expression increased the risk of unfavorable functional outcomes. Higher miR-206 expression increased the risk of spontaneous HT. These two miRNAs may be as the potential biomarkers for functional outcomes and spontaneous HT after AIS.

Background and Aims

We aimed to explore the association of serum level of the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) and its related inflammatory biomarkers (hypoxia inducible factor-1α, cathepsin B, caspase-1 and matrix metalloproteinase-9) with malignant brain edema (MBE) in patients with acute ischemic stroke.

Methods

We prospectively enrolled patients with acute ischemic stroke admitted < 24 hours from onset of symptoms. Brain CT was performed on admission and blood samples were collected. Repeated brain CT/MRI was performed <7 days of admission to identify the presence of MBE, defined as neurological deterioration with imaging signs of midline shift or compressed basal cisterns. Logistic regression analysis was performed to assess the association between inflammatory biomarkers and MBE, adjusted for age and National Institutes of Health Stroke Scale (NIHSS).

Results

200 patients (69.3±14.3 years; male 55%) were included for analysis, of whom 26 patients developed MBE (median time from stroke onset to MBE 32.5h). Compared with patients without MBE, those with MBE had higher level of serum concentration of NLRP3 (median time from onset to blood collection 3h, 1.85 ng/ml vs. 1.11 ng/ml, P=0.026). NLRP3 level was positively correlated with NIHSS on admission (Spearman ρ=0.18, P=0.01) and the association between NLRP3 and MBE was attenuated (OR 1.47, 95% CI 0.88-2.46, P=0.138) after adjusting for age and NIHSS. There was no significant difference in other biomarkers between MBE and non-MBE groups.

Conclusions

There was a trend of association between higher levels of NLRP3 and increased risks of MBE, which is worth further validation in large studies.

Background and Aims

本研究的目的是确定富含亮氨酸的 alpha-2 糖蛋白 1 (LRG1) 是否具有作为动脉瘤性蛛网膜下腔出血 (aSAH) 患者预后和严重程度生物标志物的潜力。

Methods

This observational and prospective study included 44 patients with aSAH from Nanjing Drum Tower Hospital over the period of June to December 2020. Concentrations of LRG1 in the cerebrospinal fluid (CSF) were determined by enzyme-linked immunosorbent assay (ELISA) within 24h after aSAH. We further determined the relationship of CSF LRG1 levels with disease severity and prognosis three months after aSAH.

Results

Higher CSF LRG1 levels were associated with a higher Hunt-Hess grade (p < 0.05). Using univariate analysis, it was found that poor outcomes at three months were associated with higher World Federation of Neurological Surgeons Scale (WFNS) score, higher Hunt-Hess grade, higher CSF LRG1 levels, and higher Fisher score. Logistic regression analysis revealed a significant impact of LRG1 on the poor outcomes, also after adjustment for confounding factors.

Conclusions

These findings suggest an increase in CSF LRG1 levels in aSAH patients, which may serve as a potential biomarker of unfavorable prognosis and disease severity.

Background and Aims

Quickly screening of high-risk of peptic ulcer (PU) is of great significance to avoid gastrointestinal bleeding after antiplatelet therapy. In this study, we hoped to find a fast and less invasive method for PU screening.

Methods

902 health examined population blood samples were prospectively collected, and gastroscopic assessment was performed for gastrointestinal mucosal morphology in our hospital from January 2019 to June 2020. PU was defined as a gastric or duodenal mucosal defect >5mm in diameter on gastroscopic assessment.

Results

Blood indices showed that PGI and albumin (ALB) were both independently associated with PU (all P<0.05). Based on this, we proposed a PGI and ALB Composite Score (PACS), ranged from 0-2. The ROC analysis showed that PACS had a good diagnostic ability for PU (AUC=0.774, P<0.001). The probability of PU was significantly elevated with the increase of PACS score (PACS 0 vs 1 vs 2=7.9% vs 28.6% vs 62.2%, P<0.001).

Conclusions

Both serum PGI and ALB were associated with the increased rate of PU in health examined population, and the PACS score based on these two items may be used to identify patients with high risk of PU.

Background and Aims

Ischemic stroke considers a high morbidity and mortality condition. The initial ischemic brain damage leads to robust activation of the immune system. According to the studies, numerous plasma inflammatory markers are elevated within patients with stroke than in healthy populations. It is suggesting that the different pattern of immuno-inflammatory activation is associated with stroke subtypes.

Methods

We aimed to investigate some selected cytokines in patients with Ischemic Stroke and the control group. Methods: Using the ELISA methods, were assayed cytokine levels. We evaluate the following cytokines in the present work: IL-1b, TNF alfa, IL-17, IL-23, TGF, TGF, IL-20, VEGF, and IGF-1 in both groups (ischemic stroke and Health group). In the present study, we investigated one hundred health control and Fourty free patients with ischemic stroke. Statistical analysis of experimental data was processed using GraphPad Prisma 9, P < 0.05 was statistically significant.

Results

Our study revealed that levels of IL-1b, TNF alfa, TGF, and VEGF were increased in patients with Ischemic Stroke compared to the control group (IL-1b ∼ 3.1-fold (p = 0.0002), TNF alfa ∼ 5.9-fold (p < 0.0001), TGF - ∼100 (p  =  0.0001) and VEGF- 9-fold (P=0.001), accordingly). The levels of IL-17, IL-23, IL-20, and IGF-1 were decreased in patients with Ischemic stroke compared to the Control group (IL-17 ∼ 4-fold (p=0.0001), IL-23 ∼ 2.3-fold (p = 0.001), IL-20 ∼13.2-fold (p = 0.0001), IGF-1 ∼1.1-fold (p=0.15)).

Conclusions

Thus, mentioned cytokines play an essential role in cellular signaling and regulation; accordingly, their alteration has significant implications outcome troke severity of ischemic stroke.

Background and Aims

Acute ischemic stroke (AIS) is a leading cause of disability and mortality worldwide. Prediction of penumbra existence after AIS is crucial for making decision on reperfusion therapy. We aim to investigate whether the CircOGDH is a potential biomarker for penumbra in patients with AIS and its role in ischemic neuronal damage.

Methods

CircOGDH was screened from penumbra of middle cerebral artery occlusion mice and was assessed in plasma of
patients with AIS by quantitative polymerase chain reaction. Magnetic resonance imaging was used to examine the penumbra
volumes. CircOGDH interacted with miR-5112 in primary cortical neurons was detected by fluorescence
in situ hybridization, RNA immunoprecipitation, and luciferase reporter assay. Adenovirus-mediated CircOGDH knockdown
ameliorated neuronal apoptosis induced by COL4A4 (Gallus collagen, type IV, alpha IV) overexpression. Transmission electron
microscope, nanoparticle tracking analysis, and Western blot were performed to confirm exosomes.

Results

CircOGDH expression was dramatically and selectively upregulated in the penumbra tissue of middle cerebral artery occlusion mice and in the plasma of 45 patients with AIS showing a 54-fold enhancement versus noncerebrovascular disease controls (NDCs)，which was positively correlated with the size of penumbra in AIS patients. Sequestering of miR-5112 by CircOGDH enhanced COL4A4 expression to elevate neuron damage. Additionally, knockdown of CircOGDH significantly enhanced neuronal cell viability under ischemic conditions. Furthermore, CircOGDH was found highly expressed in plasma exosomes of patients with AIS compared with those in NDCs.

Conclusions

These results demonstrate that CircOGDH is a potential therapeutic target for regulating ischemic neuronal viability, serving as a predictive biomarker of penumbra in AIS patients.

Background and Aims

The global burden of ischemic stroke necessitates the search for new factors influencing its risk and outcomes. One of the emerging risk factors is thyroid dysfunction, while thyroid hormones may have neuroprotective properties.

To clarify the effects of hypothyroidism, triiodothyronine (fT3) level on ischemic stroke risk, outcomes and related biomarkers, we adopted a Mendelian randomization approach.

Methods

We used 6 independent single nucleotide polymorphisms (SNPs), extracted from 2 GWAS-studies in Split and Dalmania cohort (Croatia) as instrumental variables, genetically predicting fT3 level. Summary-level data for ischemic stroke outcomes (mRs 0-2 vs. 3-6) was obtained from GISCOME-network. SNPs associated with hypothyroidism were extracted from the UKBiobank database. SNPs associated with 24 circulating proteins of the apoptosis system were extracted from the Genomic Atlas of the Plasma Proteome. Summary data for stroke risk was obtained from MEGASTROKE study.

Results

MR-analysis showed that genetically predicted 1-SD increase in fT3 level is associated with reduce in risk of unfavorable (mRs 3-6) stroke outcome (OR=0.76, 95%CI 0.6-0.96). There was a causative association between hypothyroidism and levels of BCL-2-associated cell death agonist (beta=3.7488, p= 0.03594), mitochondrial apoptosis-inducing factor-1 (beta=1.953, p=0.02993), lacunar stroke risk (p=0,0006). Also, causative association between deiodinase-2 expression and reduction of lacunar stoke risk was revealed (OR=0.89, 95% CI 0.82–0.97).

Conclusions

This study showed that higher fT3 levels could be causally associated with decreased risk of unfavorable ischemic stroke outcome. Underlying mechanisms may be attributed to apoptosis downregulation. Hypothyroidism is predominantly associated with lacunar stroke subtype. These findings add new evidences for neuroprotective effects of thyroid hormones.

Background and Aims

Large-scale genomic study on ischemic stroke (IS) patients is crucial for driving and generalizing precise medical prevention and treatment. Compared to the previous array-based studies, whole genome sequencing (WGS) provides essential knowledge for individual and rare variants. Here, we present the STROMICS Phase I genome study by analysis of 10241 deeply sequenced IS patients from the Third China National Stroke Registry.

Methods

Each patient was sequenced to ~40x coverage. After quality control and variation calling, genomic characteristics were explored by analyzing the allele frequencies and comparison with other biobanks. Population structure was evaluated by PCA and ADMIXTURE. Loci involved in adaptive evolution were identified by EigenGWAS. Genetic association and mendelian risk burden were analyzed.

Results

135,589,210 biallelic variants were identified, including 125,769,898 SNVs and 9,819,312 Indels. Most variants (96.18%) have allele-frequency ≤5%, and STROMICS provides 57,125,553 novel variants. A finer scale population structure was obtained for the inclusion of the low-frequency variants, and the first two principles components reflect latitude (r=0.74) and longitude (r=0.42), respectively. 18 gene loci demonstrate allele frequency adaptation across the latitude including the MTHFR-C677T polymorphism that alters folic acid and homocysteine level. Common and rare variant association study unravel 10 novel loci and 6 functional variants contributing to 6 stroke-related traits. Pathogenicity analysis on NOTCH3 loss-of-function and cysteine-altering variants explicit a broad neuro-imaging spectrum.

Conclusions

Our study establishes a large-scale and deep genomic resource of IS patients from East Asia. The findings provide opportunities for novel genetic discoveries and potential therapeutic targets of IS.