Project description:Exosomal circRNA sequencing was used to identify differentially expressed circRNAs between LAA stroke and normal controls. From a further validation stage, the results were validated using RT-qPCR.
Project description:Purpose: This study aimed to explore the differential expression profiles of exosomal lncRNAs and evaluated their potential utility in the accurate diagnosis of LAA stroke. Methods: LncRNA profiles of exosomes in large artery atherosclerosis stroke and controls were generated by high-throughput sequencing. The sequence reads that passed quality filters were analyzed at the transcript isoform level with Hisat2, Trapnell, STAR. qRT–PCR validation was performed using TaqMan and SYBR Green assays. Results: A total of 1020 differentially expressed lncRNAs were identified in LAA stroke patients. GO and KEGG pathway analyses indicated that their target genes are involved in atherosclerosis-related pathways, including inflammation, cell adhesion, and cell migration. 8 exosomal lncRNAs were confirmed with qRT–PCR.The result showed that the expression trend of differential expressed lncRNAs in validation was consistent with RNA-seq.Conclusion: Our study showed the differential expression of lncRNAs in plasma exosomes and presented related diagnostic potential for LAA stroke for the first time. The results suggested that exosomal lncRNA could be potential diagnostic tools in LAA stroke. Circular RNAs (circRNAs), novel endogenous noncoding RNAs, play diverse roles in ischemic stroke. Recently, the abundance and stability of circRNAs in exosomes have been identified. However, a comprehensive analysis of exosomal circRNAs in large artery atherosclerotic (LAA) stroke has not yet been reported. We performed RNA sequencing (RNA-Seq) to comprehensively identify differentially expressed exosomal circRNAs in five paired LAA and normal controls. RNA-Seq identified a total of 462 circRNAs in peripheral exosomes; there were 25 differentially expressed circRNAs among them. Additionally, circRNA competing endogenous RNA (ceRNA) network and translatable analysis revealed the potential functions of the exosomal circRNAs in LAA progression. Two ceRNA pathways involving 5 circRNAs, 2 miRNAs, and 3 mRNAs were confirmed by qRT-PCR. In the validation cohort, receiver operating characteristic (ROC) curve analysis identified two circRNAs as possible novel biomarkers, and a logistic model combining two and four circRNAs increased the area under the curve compared with the individual circRNAs.
Project description:BackgroundCoronary artery disease (CAD) occurs at younger age in India but only a limited number of studies have evaluated risk factors and management status. This is a multisite observational registry to assess risk factors and treatment patterns in young patients presenting with acute coronary syndrome (ACS) and stable ischemic heart disease (IHD).MethodsWe recruited 997 young patients (men <55, women <65y) presenting with ACS or stable IHD successively at 22 centers across India. Details of baseline risk factors and management status were obtained. Descriptive statistics are reported.ResultsMean age of participants was 49.1±8y, 72% were men and 68% had ACS. Family history of CAD was in 50%, diabetes 44%, hypertension 49%, history of dyslipidemia 11%, smoking/tobacco use 39%, and sedentary habits in 20%. 1.3% had "possible familial hypercholesterolemia". Metabolic risk factors (high BMI, diabetes and hypertension) were significantly greater in women (p<0.01). Women were older at diagnosis of CAD and presented more often with non-ST elevation ACS. In the study cohort antiplatelet use was in 85%, beta-blockers 38%, statins 63% and ACE inhibitors/ARBs in 41% while in ACS patients it was 80.5%, 54.6%, 80.8% and 40.8%, respectively. 35.9% patients underwent percutaneous coronary intervention while coronary bypass surgery was performed in 10.4%.ConclusionsConventional risk factors including family history continue to play a pivotal role in premature CAD in Indians. Women have more of metabolic risk factors, present at a later age and have non-ST elevation ACS more often. There is a need to focus on improving use of evidence-based drug therapies and interventions.
Project description:Objectives: The combination of systemic thrombolysis and mechanical thrombectomy is indicated in patients with ischemic stroke due to a large vessel occlusion (LVO) and these treatments are time-dependent. Rapid identification of patients with suspected LVO also in a prehospital setting could influence the choice of the destination hospital. Aim of this pilot study was to evaluate the predictive role of a new stroke scale for LVO, comparing it to other scores. Patients and Methods: All consecutive patients admitted to our comprehensive stroke center with suspected ischemic stroke were studied with a CT angiography and 5 different stroke scales were applied. The Large ARtery Occlusion (LARIO) stroke scale consists of 5 items including the assessment of facial palsy, language alteration, grip and arm weakness, and the presence of neglect. A Receiving Operating Characteristic curve was evaluated for each stroke scale to explore the level of accuracy in LVO prediction. Results: A total of 145 patients were included in the analysis. LVO was detected in 37.2% of patients. The Area Under Curve of the LARIO score was 0.951 (95%CI: 0.902-0.980), similar to NIHSS and higher than other scales. The cut-off score for best performance of the LARIO stroke scale was higher than 3 (positive predictive value: 77% and negative predictive value: 100%). Conclusion: The LARIO stroke scale is a simple tool, showing high accuracy in detecting LVO, even if with some limitations due to some false positive cases. Its efficacy has to be confirmed in a pre-hospital setting and other centers.
Project description:BackgroundThe incidence of acute ischemic stroke caused by large vessel occlusion is relatively infrequent in the young adult population. We sought to evaluate their clinical outcomes after endovascular treatment (EVT) and stroke etiology compared with older patients.MethodsWe examined data from the ANGEL-ACT registry, a nationwide study in China focusing on EVT for acute ischemic stroke. We compared two age groups: <50 years old and ≥50 years old. Our analysis focused on outcome measures such as the 90-day modified Rankin Scale (mRS) score, mortality, and symptomatic intracranial hemorrhage (sICH). We adjusted for confounding variables.ResultsWe included 1,691 patients, and 216 patients (13%) were <50 years old. Young patients had lower median National Institutes of Health Stroke Scale (NIHSS) scores (14 vs. 17, P < 0.001) and fewer cardiovascular comorbidities than older patients. Underlying intracranial atherosclerosis disease (ICAD) was higher in young patients (39.4 vs. 28.7%, P = 0.001). Clinical outcome was less favorable in older compared to younger patients (mRS shift: 0.76 [95% confidence interval (CI), 0.58-0.99]); functional independence [mRS score 0-2] 61% vs. 39% (adjusted odds ratio (OR), 0.7 [95% CI, 0.51-0.97]). Mortality and sICH did not differ between groups. Onset to puncture time (OTP) was longer in young patients (357 min vs. 294 min, P = 0.001).ConclusionAn estimated 13% of patients who underwent endovascular thrombectomy for acute ischemic stroke were <50 years old. Symptomatic underlying ICAD was more prevalent in the younger patient population. Despite a prehospital delay, younger patients exhibited more favorable outcomes than their older counterparts.
Project description:Intracranial atherosclerosis burden is an arising key index for the risk and prognosis for Intracranial Atherosclerosis Stenosis (ICAS). The present study estimated one-year prognosis for patients of symptomatic ICAS with different degrees of intracranial atherosclerosis burden (ICASB) and identified whether the category of multiple and single acute infarction was associated with atherosclerosis burden. A total of 2864 consecutive patients, from 22 hospitals across China, who experienced an acute cerebral ischemia <7 days after onset of symptoms were evaluated. All patients underwent magnetic resonance angiography, and the degree of intracranial stenosis with the ICASB was calculated. The patients were categorized into three groups according to ICASB grading: <4, 4-5 and >5scores. Multivariate Cox proportional hazards regression models were used to estimate the impact of the hazard ratios(HR) of the putative determinants of recurrent stroke in one year. In the groups with ICASB 4-5 and ICASB >5scores recurrent stroke were significantly higher than the other (P<0.0001). On multivariate logistic analysis, ICASB (4-5) indicated more stroke recurrence at 12 months (adjusted hazard ratio, 1.96; 95% confidence interval, 1.08-3.56; P=0.027), compared to the ICASB<4scores and >5 groups (P<0.001). Moreover, proportion of single and multiple infarction lesions differs with different ICASB. Multiple lesions were related with higher of ICASB(P<0.001). Intracranial atherosclerosis burden was associated with recurrent stroke at 12 months. Multiple infarction lesions were associated with higher ICASB score which indicate higher risk of recurrent.
Project description:Intracranial and extracranial large-artery atherosclerosis (LAA) are a main cause of ischemic stroke. Biomarkers may aid in the diagnosis of LAA and help to stratify patients' risk of stroke. We performed a narrative review of the literature, mainly published in the last five years, with the aim of identifying biomarkers associated either with intracranial or extracranial LAA in humans. Several potential biomarkers of LAA, mainly related to lipidic pathways and inflammation, have been studied. Diagnostic biomarkers of LAA were evaluated by measuring biomarkers levels in patients with LAA stroke and other stroke etiologies. Some biomarkers were associated with the functional prognosis of LAA stroke patients. Increased levels of IL-6 and sLOX-1 were associated with a risk of progression of carotid atherosclerotic disease. Findings support the notion that the immune system plays a central role in the pathogenesis of LAA. Overall, in most studies, results were not externally validated. In the future, biomarkers could be useful for the selection of patients for clinical trials. To adopt these biomarkers in clinical practice, we will need robust multicentric studies proving their reproducibility and a clear practical applicability for their use.
Project description:BackgroundSouth-Asian's are predisposed to early onset type 2 diabetes (T2DM). The prevalence of cardio-metabolic risk-factors in young Sri-Lankans is unknown.Methodology/principal findingsTo determine by questionnaire and anthropometry the prevalence of first degree family history (FH) of T2DM, physical inactivity, raised waist circumference (WC) and raised body mass index (BMI) in a representative healthy urban population selected by cluster sampling. Those with ? 2 risk-factors were evaluated for metabolic syndrome (MS) and recruited for an intervention trial. Of 23,296 participants screened, 22,507 (53% Female) were eligible [8,497 aged 10-14 yrs, 4,763 aged 15-19 yrs and 9,247 aged 20-40 yrs]. 51% had none of the 4 risk-factors, 26% 1 risk-factor and 23% (5,163) ? 2 risk-factors of whom 4,532 were assessed for MS. Raised BMI was noted in 19.7% aged 10-14 yrs, 15.3% between 15-19 yrs, and between 20-40 yrs, 27.4% of males vs. 21.8% of females p<0.001. Prevalence of raised WC was greater in females for each age group: 42.7% vs. 32.1%; 28.1% vs. 16.1%; 34.5% vs. 25.7% (p<0.05 for all) as was physical inactivity: 39.9% vs. 14.5%; 51.7% vs. 20.0%; 62.7% vs. 41.3% which rose in both sexes with age (p<0.05 for all). FH of T2DM was present in 26.2%. In 4532 (50%<16 yrs) with ? 2 risk-factors, impaired fasting glycaemia/impaired glucose tolerance (pre-diabetes) prevalence was 16%. MS was more prevalent in males [10-16 yrs (13.0% vs. 8.8%), 16-40 yrs (29.5% vs. 20.0%) p<0.001 for both].Conclusions/significanceThere is a high prevalence of modifiable cardio-metabolic risk-factors in young urban Sri-Lankans with significant gender differences. A primary prevention intervention trial is ongoing in this cohort. Clinical Trial Registration Number SLCTR/2008/World Health Organization (WHO) international clinical trial registry platform.