Jin Pyeong Jeon

A Novel Association between Lysyl Oxidase Gene Polymorphism and Intracranial Aneurysm in Koreans

Purpose Lysyl oxidase (LOX) controls the cross-linking and maturation of elastin and collagen fibers. In this study, we investigated the association between LOX gene polymorphisms and intracranial aneurysm (IA) formation in a homogeneous Korean population. Materials and Methods This cross-sectional study involved 80 age-sex matched patients with IA and controls. Fishers exact test was performed to analyze allelic associations between ten single nucleotide polymorphisms (SNPs) and IA, including 41 ruptured and 39 unruptured cases. Haplotype-specific associations were analyzed using the omnibus test estimating asymptotic chi-square statistics. Results Of ten SNPs, three SNPs (rs2303656, rs3900446, and rs763497) were significantly associated with IA (p<0.01). The C allele of rs3900446 was significantly related to increased IA risk with a significant threshold [odds ratio (OR)=20.15, p=4.8×10−5]. Meanwhile, the A allele of rs2303656 showed a preventive effect against IA formation (p=8.2×10−4). Seventeen of 247 haplotype structures showed a suggestive association with IA (asymptotic p<0.001). Of ten SNP haplotype combinations, the CG combination of rs3900446 and rs763497 reached Bonferroni-adjusted significant threshold in IA patients (minor haplotype frequency=0.113, asymptotic p=1.3×10−5). However, there was no association between aneurysm rupture and the LOX gene. Conclusion This preliminary study indicated that LOX gene polymorphisms, such as rs2303656, rs3900446, and rs763497, may play crucial roles in IA formation in the Korean population. Our novel findings need to be validated in a large-scale independent population.

Delayed Cerebral Ischemia and Vasospasm After Spontaneous Angiogram-Negative Subarachnoid Hemorrhage: An Updated Meta-Analysis

OBJECTIVEnTo report clinical outcomes of delayed cerebral ischemia (DCI) and vasospasm in angiogram-negative subarachnoid hemorrhage (SAH) according to hemorrhage patterns, perimesencephalic hemorrhage (PMH) and non-PMH.nnnMETHODSnOnline databases from January 1990 to December 2017 were systematically reviewed. A fixed-effects model was used to control heterogeneity. To resolve publication bias, the trim and fill method was used to estimate number of missing studies and adjusted odds ratio (OR). Subgroup analysis of data from studies that defined angiogram-negative subarachnoid hemorrhage by angiography repeated at least twice or computed tomography angiography was performed.nnnRESULTSnAmong 24 studies including 2083 patients, 23/985 patients (2.3%) with PMH and 144/1098 patients (13.1%) with non-PMH had DCI, indicating that patients with PMH experienced significantly lower DCI than patients with non-PMH (ORxa0= 0.219; 95% confidence interval [CI], 0.144-0.334). Regarding vasospasm, 99/773 patients (12.8%) with PMH and 231/922 patients (25.1%) with non-PMH exhibited vasospasm, indicating that patients with PMH experienced significantly lower vasospasm than patients with non-PMH (ORxa0= 0.445; 95% CI, 0.337-0.589). Funnel plots show asymmetry indicating possible publication bias. After trimming 10 studies for DCI and 7 for vasospasm, the adjusted ORs remained significant between PMH and lower risks of DCI and vasospasm. Subgroup analysis of 789 patients in 8 studies showed a lower risk of DCI (ORxa0=xa00.268; 95% CI, 0.151-0.473) and vasospasm (ORxa0= 0.346; 95% CI, 0.221-0.538) in patients with PMH.nnnCONCLUSIONSnPMH showed a significantly lower risk of DCI and vasospasm than non-PMH. Clinical outcomes of angiogram-negative subarachnoid hemorrhage, based on meta-analysis of individual patient data, need to be investigated.

Prediction of persistent hemodynamic depression after carotid angioplasty and stenting using artificial neural network model

OBJECTIVESnTo assess and compare predictive factors for persistent hemodynamic depression (PHD) after carotid artery angioplasty and stenting (CAS) using artificial neural network (ANN) and multiple logistic regression (MLR) or support vector machines (SVM) models.nnnPATIENTS AND METHODSnA retrospective data set of patients (n=76) who underwent CAS from 2007 to 2014 was used as input (training cohort) to a back-propagation ANN using TensorFlow platform. PHD was defined when systolic blood pressure was less than 90mmHg or heart rate was less 50 beats/min that lasted for more than one hour. The resulting ANN was prospectively tested in 33 patients (test cohort) and compared with MLR or SVM models according to accuracy and receiver operating characteristics (ROC) curve analysis.nnnRESULTSnNo significant difference in baseline characteristics between the training cohort and the test cohort was observed. PHD was observed in 21 (27.6%) patients in the training cohort and 10 (30.3%) patients in the test cohort. In the training cohort, the accuracy of ANN for the prediction of PHD was 98.7% and the area under the ROC curve (AUROC) was 0.961. In the test cohort, the number of correctly classified instances was 32 (97.0%) using the ANN model. In contrast, the accuracy rate of MLR or SVM model was both 75.8%. ANN (AUROC: 0.950; 95% CI [confidence interval]: 0.813-0.996) showed superior predictive performance compared to MLR model (AUROC: 0.796; 95% CI: 0.620-0.915, p<0.001) or SVM model (AUROC: 0.885; 95% CI: 0.725-0.969, p<0.001).nnnCONCLUSIONSnThe ANN model seems to have more powerful prediction capabilities than MLR or SVM model for persistent hemodynamic depression after CAS. External validation with a large cohort is needed to confirm our results.

The Incidence of Hydrocephalus and Shunting in Patients with Angiogram-Negative Subarachnoid Hemorrhage: An Updated Meta-Analysis

OBJECTIVEnTo evaluate the incidence of hydrocephalus and implanted shunts in angiogram-negative subarachnoid hemorrhage (SAH) according to hemorrhage patterns: perimesencephalic SAH (PMH) versus non-PMH.nnnMETHODSnThe online database literature from January 1990 to November 2017 was systematically reviewed. A fixed-effect model was used when heterogeneity was <50%. A Begg funnel plot was used to assess publication bias. An additional trim and fill method was used to estimate the number of missing studies. A subgroup analysis with studies, which defined angiogram-negative SAH using repeated angiography or computed tomography angiography, was further performed.nnnRESULTSnA total of 28 articles including 2577 patients were enrolled. Patients with PMH showed a significantly decreased incidence of hydrocephalus (odds ratio [OR], 0.269; 95% confidence interval [CI], 0.208-0.348) and shunts (OR, 0.263; 95% CI, 0.169-0.411) than did patients without PMH. A subgroup analysis of 7 studies with 675 patients showed less hydrocephalus in patients with PMH than in patients without PMH (OR, 0.358; 95% CI, 0.161-0.793), with possible publication bias. Shunt procedures were marginally less common in patients with PMH compared with those patients without PMH (OR, 0.490; 95% CI, 0.236-1.018) with possible publication bias. After correction of the forest plot, the adjusted OR was 0.617 (95% CI, 0.251-1.513) for hydrocephalus and 0.618 (95% CI, 0.310-1.232) for shunts, suggesting no significant relationships between PMH and the risk of hydrocephalus or shunting.nnnCONCLUSIONSnHydrocephalus and shunts were more evident in non-PMH than PMH. However, subgroup analyses did not show significant associations between PMH and lower risks of these events after correction for possible publication bias. Further meta-analyses based on individual patient data are necessary.

Expression of alpha 1 intensities in haptoglobin 2-1 and its association with clinical course in aneurysmal subarachnoid hemorrhage

P and Co-expression Network Analysis of Immune-Related Genes in Short-term Calorie Restricted Mice RNA-seq technology was performed a comparative transcriptome analysis of the MMTV-TGF-α female mice thymus tissues that were fed ad libitum (AL), cronic calorie restriction (CCR) (85% of AL fed mice) and intermittent calorie restriction (ICR) (3 weeks AL fed, 1 week 40% of AL fed mice) from 10 weeks of age to 17 weeks of age or 18 weeks of age. The results of RNA-seq analysis, a total of 6091 significantly differentially expressed genes (DEGs) were identified. 2821, 2825 and 445 significantly DEGs were detected between AL-CCR, CCR-ICR and AL-ICR fed groups, respectively. These DEGs were classified according to cellular components, biological processes and molecular functions Gene Ontology (GO) main categories. 188 of 2821, 36 of 445, 176 of 2825 genes were identified to be involved in immune system process (GO:0002376) biological processes GO categories. KEGG pathway and the gene co-expression network analysis between AL-CCR, CCR-ICR and AL-ICR fed groups immune-related DEGs were done using String database. For network analysis, nodes and edges were presented the interaction between immune-related DEGs.Calorie restriction is to reduce the amount of calorie received without malnutrition. This manipulation method has positive effects on life span, cancer formation and immune response in the long run. However, there are also some systems such as lymph organs that respond quickly to lack of calories. Thymus is one of these lymph organs. In this study, two type calorie restriction practices (CCR/ICR) were used on MMTV-TGFα transgenic mice and a group of mice were fed ad libitum (AL) as a control group. It is aimed to determine the changes that the nutrition type will bring about in the expression of genes. The manipulation started at the 10th week of the life of the mice and ended at the 17th and 18th week. RNA-Seq-based transcriptome were performed to the RNAs obtained from the thymus of the sacrificed mice. Through RNA-Seq results “Differential Expressed Genes” (DEGs) were determined. 6091 of them have been identified as statistically significant (p <0.05). The AKT1, CTCF, PTEN genes known to cause breast tumor development were selected by data banks. The selected genes were searched in three different RNA-Seq data and expression levels were determined for three genes in three different medium. Changes in expression level are displayed via graphics .

Ultrasonographic optic nerve sheath diameter to detect increased intracranial pressure in adults: a meta-analysis:

Background The optimal optic nerve sheath diameter (ONSD) cut-off for identifying increased intracranial pressure (IICP) remains unclear in adult patients. Purpose To validate the diagnostic accuracy of ultrasonographic (US) ONSDu2009>u20095.0u2009mm as a cut-off for detecting IICP by computed tomographic (CT) through a meta-analysis. Material and Methods A systemic literature review was performed of online databases from January 1990 to September 2017. A bivariate random-effects model was used to estimate pooled sensitivity, specificity, and diagnostic odds ratio (DOR) with 95% confidence intervals (CIs). A summary receiver operating characteristic (SROC) graph was used to provide summary points for sensitivity and specificity. Meta-regression tests were performed to estimate the influence of the study characteristics on DOR. Publication bias was assessed using Deeks funnel plot asymmetry test. Results Six studies with 352 patients were included in the meta-analysis. US ONSDu2009>u20095.0u2009mm revealed pooled sensitivity of 99% (95% CIu2009=u200996–100) and specificity of 73% (95% CIu2009=u200965–80) for IICP detection. DOR was 178. The area under the SROC curve was 0.981, indicating a good level of accuracy. Meta-regression studies showed no significant associations between DOR and study characteristics such as probe mode (relative DOR [RDOR]u2009=u20090.60; Pu2009=u20090.78), study quality (RDORu2009=u20090.52; Pu2009=u20090.67), IICP prevalence (RDORu2009=u20090.04; Pu2009=u20090.17), or pathology at admission (RDORu2009=u20091.30; Pu2009=u20090.87). Conclusion US ONSDu2009>u20095.0u2009mm can be used to rapidly detect IICP in adults in emergency departments and intensive care units. Further meta-analysis based on individual patient-level databases is needed to confirm these results.

Association of SOX17 Gene Polymorphisms and Intracranial Aneurysm: A Case-Control Study and Meta-Analysis

BACKGROUNDnGenome-wide association studies have revealed an association between SRY-box 17 (SOX17) gene and intracranial aneurysm (IA) formation. However, results were mainly derived from European and Japanese populations. We investigated the association between SOX17 gene polymorphisms and IA in a homogeneous Korean population. We performed a meta-analysis to assess these results in East-Asian populations.nnnMETHODSnThis cross-sectional study included 187 age- and sex-matched patients with IA and 372 control subjects. Genetic association analysis was performed in the generalized linear model to identify associations between 4xa0single nucleotide polymorphisms and IA, including 95xa0patients with ruptured aneurysms and 92 with unruptured aneurysms. The East-Asian meta-analysis of 5100 IA cases and 7930 control cases was conducted under an inverse variance model.nnnRESULTSnAmong 4 single nucleotide polymorphisms that passed quality control tests, the minor C allele of rs1072737 was significantly associated with IA (odds ratio 0.69, 95% confidence interval 0.49-0.96, Pxa0= 0.03). None of the 4 single nucleotide polymorphisms showed a significant association between patients with ruptured and unruptured aneurysms. Meta-analysis revealed that Gxa0alleles of rs10958409 and rs9298506 were significantly associated with IA in the East-Asian population after removing study heterogeneity (odds ratio 1.11, 95% confidence interval 1.04-1.19, Pxa0= 0.0023 and odds ratio 1.19, 95% confidence interval 1.07-1.32, Pxa0= 0.0016).nnnCONCLUSIONSnIdentification of genetic variants located near SOX17 is likely to be clinically significant for IA formation. rs10958409 and rs9298506 may increase risk of IA in East-Asian populations. Our findings may help in the identification of IA pathogenesis.

Stent-assisted modified coil protection technique for bilobulated aneurysm: technical note

Endovascular treatment of deeply located bilobulated aneurysms in elderly patients is still challenging because of the acute angulation of the carotid siphon and poor microcatheter support. In particular, generating a frame coil to cover each lobe is difficult in bilobulated aneurysms with narrow isthmus in the fused portion. Here, we report a successfully treated bilobulated aneurysm using a modified coil protection technique with stent assistance.

Primary suction thrombectomy for acute ischemic stroke: A meta-analysis of the current literature

OBJECTIVESnWe conducted a meta-analysis to assess the angiographic and clinical outcomes for ischemic stroke patients treated with primary suction thrombectomy and to compare the procedural outcomes based on the treatment strategies (primary suction vs. stent retriever thrombectomy).nnnPATIENTS AND METHODSnWe conducted a systemic literature review through an online data base from January 2004 through December 2016. The primary outcomes were rate of successful recanalization on final angiogram and good outcome three months after stroke onset. We used a fixed-effect model in cases with heterogeneity <50%.nnnRESULTSnFifteen articles were included. Primary suction thrombectomy achieved a successful recanalization rate of 85.2% (95% confidence interval [CI]: 79.9%-89.3%), a good clinical outcome rate of 52.7% (95% CI: 49.3%-56.2%) after the three-month follow-up, a mortality rate of 13.0% (95% CI: 8.9%-18.5%) and a symptomatic intracranial hemorrhage rate of 6.2% (95% CI: 4.8%-8.0%). The rates of recanalization (odds ratio [OR], 1.064; 95% CI: 0.202-5.608; p=0.571) and good outcomes (OR, 0.920; 95% CI: 0.570-1.486; p=0.735) did not differ significantly between primary suction thrombectomy and stent retriever thrombectomy.nnnCONCLUSIONnPrimary suction thrombectomy produced higher recanalization and good clinical outcome rates than did stent retriever thrombectomy. Larger-scale studies are necessary that consider factors such as occlusion site, stroke severity, and concomitant use of endovascular devices.

Endovascular treatment of acute ischemic stroke in octogenarians: A meta-analysis of observational studies

OBJECTIVESnThe aim of this study is to compare procedural outcomes after endovascular treatment (EVT) according to age (≥80 years vs. <80 years) and to examine treatment outcomes after mechanical thrombectomy using a stent retriever between the different age groups.nnnPATIENTS AND METHODSnA systemic literature review of an online database of articles published from January 2004 to February 2017 was conducted. The primary outcome was successful recanalization in the final angiogram and symptomatic intracranial hemorrhage (S-ICH) after EVT. The secondary outcome was good clinical outcome and mortality at 3 months. A random-effect model was used in cases of heterogeneity over 50%.nnnRESULTSnEight articles including 1711 patients compared outcomes according to age. Successful recanalization did not differ significantly between the two groups (≥80 years, n=214 (70.6%);<80years, n=1035 (73.5%); OR: 0.797; 95% CI: 0.599-1.060). Age ≥80 years did not significantly increase the risk of S-ICH (OR: 1.271; 95% CI: 0.784-2.060). Octogenarians showed lower good clinical outcome at 3 months (OR: 0.323; 95% CI: 0.233-0.448) and higher mortality (OR: 2.689; 95% CI: 2.050-3.527). Three studies including 670 patients (≥80 years, n=140;<80years, n=530) assessed outcomes after mechanical thrombectomy using a stent retriever. Successful recanalization (OR: 0.786; 95% CI: 0.507-1.218) and S-ICH (OR: 1.679; 95% CI: 0.918-3.071) did not significantly differ between the two groups.nnnCONCLUSIONSnProcedural outcomes such as successful recanalization and S-ICH after EVT in octogenarians are comparable to those seen in patients <80years. EVT is technically feasible to treat hyperacute stroke in octogenarians. Further large-scale studies dealing with various factors, such as occlusion site, stroke severity, comorbidities, and concomitant use of endovascular devices are required.