Role of frailty in predicting outcomes after stroke: a systematic review and meta-analysis.

Background: Stroke is considered the second most common cause of death and the third leading cause of disability worldwide. Frailty, characterized by increased vulnerability to stressors, is emerging as a key factor affecting outcomes in older adults and stroke patients. This study aimed to estimate the prevalence of frailty in acute stroke patients and assess its association with mortality and poor functional outcome. Methods: Medline, Google Scholar, and Science Direct databases were systematically searched for English-language studies that included adult stroke patients (>16 years), have defined frailty, and reported mortality and functional outcomes. Meta-analysis was done using STATA 14.2, and the results were expressed as pooled odds ratios (OR) with 95% confidence intervals (CI). Heterogeneity was assessed using the I2 statistic and the Chi-square test. Study quality was evaluated using the Newcastle Ottawa Scale (NOS). Results: Twenty-five studies were included in the analysis. Frailty prevalence in stroke patients was 23% (95% CI 22% - 23%). Unadjusted analysis showed an OR of 2.66 (95% CI: 1.93 - 3.67) for mortality and 2.04 (95% CI: 1.49 - 2.80) for poor functional outcome. Adjusted estimates indicated an OR of 1.22 (95% CI: 1.1 - 1.35) for mortality and 1.21 (95% CI: 1.04 - 1.41) for poor functional outcome, with substantial heterogeneity for both adjusted and unadjusted analyses. No publication bias was detected for the prevalence of frailty. However, there was a publication bias for the association between frailty and mortality. Conclusions: Frailty was significantly associated with increased mortality and poorer functional outcomes in stroke patients. Our study highlights the need to focus on frailty in stroke patients to improve outcomes and quality of life. Further research should aim to standardize assessment of frailty and reduce heterogeneity in study outcomes. Systematic review registration: https://www.crd.york.ac.uk/prospero/#searchadvanced, CRD42023470325.

APAview: A web-based platform for alternative polyadenylation analyses in hematological cancers.

Background: Hematologic malignancies, such as acute promyelocytic leukemia (APL) and acute myeloid leukemia (AML), are cancers that start in blood-forming tissues and can affect the blood, bone marrow, and lymph nodes. They are often caused by genetic and molecular alterations such as mutations and gene expression changes. Alternative polyadenylation (APA) is a post-transcriptional process that regulates gene expression, and dysregulation of APA contributes to hematological malignancies. RNA-sequencing-based bioinformatic methods can identify APA sites and quantify APA usages as molecular indexes to study APA roles in disease development, diagnosis, and treatment. Unfortunately, APA data pre-processing, analysis, and visualization are time-consuming, inconsistent, and laborious. A comprehensive, user-friendly tool will greatly simplify processes for APA feature screening and mining. Results: Here, we present APAview, a web-based platform to explore APA features in hematological cancers and perform APA statistical analysis. APAview server runs on Python3 with a Flask framework and a Jinja2 templating engine. For visualization, APAview client is built on Bootstrap and Plotly. Multimodal data, such as APA quantified by QAPA/DaPars, gene expression data, and clinical information, can be uploaded to APAview and analyzed interactively. Correlation, survival, and differential analyses among user-defined groups can be performed via the web interface. Using APAview, we explored APA features in two hematological cancers, APL and AML. APAview can also be applied to other diseases by uploading different experimental data.

The alleles of AGT and HIF1A gene affect the risk of hypertension in plateau residents.

Plateau essential hypertension is a common chronic harmful disease of permanent residents in plateau areas. Studies have shown some single nucleotide polymorphisms (SNPs) associations with hypertension, but few have been verified in plateau area-lived people. In this paper, we examined some hypertension-related gene loci to analyze the relationship between risk SNPs and plateau essential hypertension in residents in Qinghai-Tibet plateau area. We screened hypertension-related SNPs from the literature, Clinvar database, GHR database, GTR database, and GWAS database, and then selected 101 susceptible SNPs for detection. Illumina MiSeq NGS platform was used to perform DNA sequencing on the blood samples from 185 Tibetan dwellings of Qinghai, and bioinformatic tools were used to make genotyping. Genetic models adjusted by gender and age were used to calculate the risk effects of genotypes. Four known SNPs as well as a new locus were found associated with PHE, which were rs2493134 (AGT), rs9349379 (PHACTR1), rs1371182 (CYP2C56P-PRPS1P1), rs567481079 (CYP2C56P-PRPS1P1), and chr14:61734822 (HIF1A). Among them, genotypes of rs2493134, rs9349379, and rs567481079 were risk factors, genotypes of rs1371182 and chr14:61734822 were protective factors. The rs2493134 in AGT was found associated with an increased risk of the plateau essential hypertension by 3.24-, 3.24-, and 2.06-fold in co-dominant, dominant, and Log-additive models, respectively. The rs9349379 in PHACTR1 is associated with a 2.61-fold increased risk of plateau essential hypertension according to the dominant model. This study reveals that the alleles of AGT, HIF1A, and PHACTR1 are closely related to plateau essential hypertension risk in the plateau Tibetan population.

Pharmacological Targets and the Biological Mechanisms of Formononetin for Alzheimer's Disease: A Network Analysis.

BACKGROUND This study aimed to identify the pharmacological targets and mechanisms of action of the traditional Chinese medicine, formononetin, in the treatment of Alzheimer's disease (AD) using network pharmacological analysis. MATERIAL AND METHODS Targets of AD were obtained by using DisGeNET gene discovery platform, the herbal ingredients target (HIT) database, the SuperPred, and the SwissTargetPrediction compound target prediction platforms. Pathogenic and therapeutic targets were imported to the STRING biological database, and Cytoscape network integration software was used to construct component-target and disease-target interaction networks. Core targets were identified by topological analysis and were further tested to identify the biological processes and signaling pathways. RESULTS Seven key target genes for formononetin in the treatment of patients with AD were identified, including estrogen receptor alpha (ESR1), peroxisome proliferator-activated receptor gamma (PPARG), tumor protein p53 (TP53), sirtuin 1 (SIRT1), tumor necrosis factor (TNF), cytochrome P450 19A1 (CYP19A1), and nuclear factor (erythroid-derived 2)-like 2 (NFE2L2). The biological processes included hormone metabolism, regulation of nucleoside, nucleotide and nucleic acid metabolism, apoptosis, energy pathways, metabolism, cell communication, and signal transduction. The signaling pathways included histone acetylation and deacetylation (HDAC) class I, regulation of p38-alpha/beta, p38 mitogen-activated protein kinase (MAPK) signaling pathway, bone morphogenetic protein (BMP) receptor signaling, interleukin-1 (IL1) mediated signaling events, the tumor necrosis factor (TNF) receptor signaling pathway, and cytoplasmic and nuclear Smad2/3 signaling. CONCLUSIONS Pharmacological network analysis was used to identify the gene targets and mechanisms of formononetin treatment in patients with AD.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: Phenotypic and mutational spectrum in patients from mainland China.

AIMS: To analyze the NOTCH3 gene mutations in patients from mainland China clinically suspected to have cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and evaluate large intracranial arteries in CADASIL patients. METHODS: We performed clinical, neuroimaging and NOTCH3 gene (exons 2-23) examinations in 47 subjects from 34 families. Large intracranial arteries were assessed using magnetic resonance angiography (MRA) in 19 cases with NOTCH3 gene variants. RESULTS: Screening of exons 3 and 4 identified six different known mutations in eight families and two novel mutations in two families. Further screening of the remaining exons identified p.R1175W, a variant of unknown significance. The incidence of NOTCH3 mutations was 29.4% (10/34). Five cases with NOTCH3 mutations showed intracranial atherosclerosis. One patient developed cerebral infarction due to left middle cerebral artery occlusion (M2 segment). CONCLUSIONS: The NOTCH3 mutation spectrum in our group was diverse and consistent with those in Caucasians but differed from those in Korea and Taiwan. The screening strategy used in Caucasian populations can be applied to mainland Chinese patients. Atherosclerosis of the large intracranial arteries involvement does not exclude CADASIL diagnosis.

Increased visibility of deep medullary veins in leukoaraiosis: a 3-T MRI study.

Cerebral venous collagenosis has been implicated in leading to white matter hyperintensities (WMHs) via venous ischemia. We sought to determine whether cerebral venous dilation or ischemia correlate with the severity of WMHs by quantitative in vivo imaging techniques. This was an investigator-initiated prospective single-center study. We reviewed clinical, laboratory data from 158 consecutive WMHs patients and 50 controls, and measured the number of voxels of deep medullary veins (DMVs) on susceptibility-weighted image and assessed the WMH volume (as a marker of the severity of WMHs) on a 3-T magnetic resonance system. We then performed the logistic-regression analysis and partial Pearson's correlation analysis to examine the association between the venous voxel count and WMH volume. The number of voxels of DMVs was significantly higher in WMHs than in controls. Increased number of voxels of DMVs was independently associated with both WMH volume of the whole brain and coregistered regional WMH volume after adjusting for age and number of lacunes. Our study indicates that cerebral deep venous insufficiency or ischemia play a role in the pathogenesis of WMHs, which may provide prognostic information on patients with WMHs and may have implications for therapeutic interventions.

[Impact of cerebral microbleeds on outcomes of acute ischemic stroke treated with intravenous thrombolysis].

OBJECTIVE: To assess the impact of cerebral microbleeds (CMBs) on clinical outcomes in patients with acute ischemic stroke treated by intravenous thrombolysis. METHODS: The clinical data of 225 patients with acute ischemic stroke who received intravenous recombinant tissue plasminogen activator therapy in the Second Affiliated Hospital, Zhejiang University School of Medicine from June 2009 to May 2013 were reviewed. The severity of CMBs and hemorrhagic transformation (HT) after thrombolytic therapy and clinical neurological outcome based on modified Rankin scale (mRS) at 3 months were evaluated. Favorable outcome was defined as mRS 0-1 and unfavorable outcome as mRS 2-6. Multivariate logistic-regression analysis and binary logistic-regression were used to determine independent risk factors of HT and favorable outcome. RESULTS: The mean age of 225 patients was (66.29±13.01) y, 73 (32.4%) patients were women, mean pretreatment National Institutes of Health Stroke Scale (NIHSS) score was 11.40±5.89, and onset-to-needle time was (238.40±89.16) min. Totally, 522 CMBs were detected in 91 patients (36.1%). Postlytic radiological HT was found in 64 patients (28.4%), among which 43 (19.1%) were hemorrhagic infarction and 21 (9.3%) were parenchymal hematoma. Univariate analysis showed that patients with HT had higher NIHSS score and more incidence of atrial fibrillation and that patients with unfavorable outcome were older and had higher NIHSS score and more CMBs. Multivariate logistic regression analysis showed that multiple CMBs (>=3) was independently associated with parenchymal hematoma (OR=4.957, 95%CI 1.306-18.811, P=0.019), but not with hemorrhagic infarction (OR=1.204, 95%CI 0.386-3.754, P=0.749). Binary logistic regression analysis showed that multiple CMBs (>=3) was independently associated with unfavorable outcome (OR=3.496, 95%CI 1.381-8.849, P=0.008). CONCLUSION: Multiple CMBs are correlated with parenchymal hematoma and unfavorable neurological outcome after thrombolytic therapy in patients with acute ischemic stroke.

[Impact of atrial fibrillation on clinical outcome in patients with acute ischemic stroke undergoing thrombolytic therapy].

OBJECTIVE: To investigate the impact of atrial fibrillation (AF) on clinical outcomes in patients with acute ischemic stroke undergoing thrombolytic therapy. METHODS: The clinical data of 330 patients with acute ischemic stroke who received intravenous recombinant tissue plasminogen activator (rt-PA) therapy in the Second Affiliated Hospital, Zhejiang University School of Medicine between June 2009 and August 2013 were reviewed. Clinical outcomes in AF and non-AF groups were evaluated by univariate and multivariate analysis. Favorable outcome was defined as a modified Rankin Scale (mRS) 0-2 on day 90. Hemorrhagic transformation (HT) was classified as hemorrhagic infarction (HI) and parenchymal hematoma (PH) within the first 24h according to ECASS II criteria. Hypoperfusion and severe hypoperfusion were defined as Tmax >6 s and >8 s, respectively. The rate of reperfusion was compared between AF and non-AF groups. RESULTS: Among 330 patients, 137(41.5%) had AF. Compared with non-AF patients, patients with AF were older [(71.7±11.5)y vs (63.4±13.2)y, P<0.001], had higher baseline National Institutes of Health Stroke Scale [IQR, 13(8-16) vs 9(5-15), P<0.001], higher rate of HT(HI: 28.5% vs 17.1%, P=0.015; PH: 13.9% vs 4.1%, P=0.002), and lower rate of favorable outcome (41.5% vs 58.0%, P=0.005) at d 90. After adjustment, AF was not a risk factor for favorable outcome (OR=0.920, 95%CI:0.533-1.586; P=0.763) and mortality (OR=1.381, 95%CI:1.096-1.242; P=0.466) on day 90. AF was also not associated with HI (OR=1.676, 95%CI: 0.972-3.031; P=0.088), but it increased the rate of PH (OR=3.621, 95%CI: 1.403-9.344; P=0.008). Among 94 patients with pre- and post-thrombolytic perfusion-weighted image, AF was not associated with increased rate of reperfusion for hypoperfusion (Tmax >6 s, OR=1.12, 95%CI: 0.35-3.63, P=0.849), but was correlated with increased rate of reperfusion for severe hypoperfusion (Tmax>8 s, OR=10.57, 95%CI:1.16-96.50, P=0.037). CONCLUSION: The presence of AF has no independent impact on neurological outcome in thrombolytic patients with acute ischemic stroke. It is associated with increased reperfusion rate of more severe hypoperfusion area and higher frequency of PH.

[Risk factors of hemorrhagic transformation in different locations and its relation to clinical outcomes of patients with acute ischemic stroke following intravenous thrombolysis].

OBJECTIVE: To investigate the risk factors of hemorrhagic transformation (HT) in different cerebral regions and to explore its relation to clinical outcomes of patients with acute ischemic stroke after intravenous thrombolysis therapy. METHODS: The clinical, laboratory, and radiological data of 292 consecutive acute ischemic stroke patients undergoing intravenous thrombolysis therapy in Second Affiliated Hospital, Zhejiang University School of Medicine from June 2009 to May 2013 was retrospectively analyzed. Deep HT was defined as HT located in basal ganglia, internal capsule, external capsule and thalamus, otherwise the lesion was defined as non-deep HT. Patients were divided into 3 groups [Deep HT(n=47), non-deep HT(n=82), non HT(n=8)] and the differences in clinical and demographic characteristics were compared by using one-way analysis of variance and Ξ2-test. Multivariable logistic regression models were used to determine the independent risk factors of HT in different cerebral regions and clinical outcomes. RESULTS: Age, baseline National Institutes of Health Stroke Scale (NIHSS) score, baseline systolic blood pressure and the frequency of atrial fibrillation were different among three groups. Logistic regression analysis revealed that baseline NIHSS score (OR=1.126, 95%CI:1.063-1.193, P<0.001) and baseline systolic blood pressure (OR=0.982, 95%CI:0.967-0.998, P=0.020) were independent risk factors of deep HT. Multivariate analysis also found that deep HT was an independent predictor of functional outcome after thrombolysis (OR=0.291, 95%CI:0.133-0.640, P=0.002). CONCLUSION: Baseline NIHSS score and systolic blood pressure are predictors for deep hemorrhagic transformation, which indicates the poor functional outcome of patients with acute ischemic stroke following thrombolytic therapy.