Objective: : We performed an expanded multi-ethnic meta-analysis to identify associations between inflammation-related loci with intracranial aneurysm (IA) susceptibility. This meta-analysis possesses increased statistical power as it is based on the most data ever evaluated. Methods: : We searched and reviewed relevant literature through electronic search engines up to August 2022. Overall estimates were calculated under the fixed- or random-effect models using pooled odds ratio (OR) and 95% confidence intervals (CIs). Subgroup analyses were performed according to ethnicity. Results: : Our meta-analysis enrolled 15 studies and involved 3070 patients and 5528 controls including European, Asian, Hispanic, and mixed ethnic populations. Of 17 inflammation-related variants, the rs1800796 locus (interleukin [IL]-6) showed the most significant genome-wide association with IA in East-Asian populations, including 1276 IA patients and 1322 controls (OR, 0.65; 95% CI, 0.56–0.75; p=3.24×10-9) under a fixed-effect model. However, this association was not observed in the European population (OR, 1.09; 95% CI, 0.80–1.47; p=0.5929). Three other variants, rs16944 (IL-1β), rs2195940 (IL-12B), and rs1800629 (tumor necrosis factor-α) showed a statistically nominal association with IA in both the overall, as well as East-Asian populations (0.01Conclusion : Our updated meta-analysis with increased statistical power highlights that rs1800796 which maps on the IL-6 gene is associated with IA, and in particular confers a protective effect against occurrence of IA in the East-Asian population.

Although technological advances and clinical studies on stem cells have been increasingly reported in stroke, research targeting hemorrhagic stroke is still lacking compared to that targeting ischemic stroke. Studies on hemorrhagic stroke are also being conducted, mainly in the USA and China. However, little research has been conducted in Korea. In reality, stem cell research or treatment is unfamiliar to many domestic neurosurgeons. Nevertheless, given the increased interest in regenerative medicine and the increase of life expectancy, attention should be paid to this topic. In this paper, we summarized pre-clinical rodent studies and clinical trials using stem cells for hemorrhagic stroke. In addition, we discussed results of domestic investigations and future perspectives on stem cell research for a better understanding.

Objective: : Cerebrospinal fluid leakage related complications (CLC) occasionally occur after intradural spinal surgery. We sought to investigate the effectiveness of early ambulation after intradural spinal surgery and analyze the risk factors for CLC. Methods: : For this retrospective cohort study, we enrolled 314 patients who underwent intradural spinal surgery at a single institution. The early group contained 79 patients who started ambulation after 1 day of bedrest without position restrictions, while the late group consisted of 235 patients who started ambulation after at least 3 days of bed rest and were limited to the prone position after surgery. In the early group, Prolene 6–0 was used as the dura suture material, while black silk 5–0 was used as the dura suture material in the late group. Results: : The overall incidence rate of CLC was 10.8%. Significant differences between the early and late groups were identified in the rate of CLC (2.5% vs. 13.6%), surgical repair required (1.3% vs. 7.7%), and length of hospital stay (2.99 vs. 9.29 days) (p<0.05). Logistic regression analysis revealed that CLC was associated with practices specific to the late group (p=0.011) and the revision surgery (p=0.022). Conclusion : Using Prolene 6–0 as a dura suture material for intradural spinal surgery resulted in lower CLC rates compared to black silk 5–0 sutures despite a shorter bed rest period. Our findings revealed that suture - needle ratio related to dura defect was the most critical factor for CLC. One-day ambulation after primary dura closure using Prolene 6–0 sutures appears to be a cost-effective and safe strategy for intradural spinal surgery.

Objective: : Cerebrospinal fluid leakage related complications (CLC) occasionally occur after intradural spinal surgery. We sought to investigate the effectiveness of early ambulation after intradural spinal surgery and analyze the risk factors for CLC. Methods: : For this retrospective cohort study, we enrolled 314 patients who underwent intradural spinal surgery at a single institution. The early group contained 79 patients who started ambulation after 1 day of bedrest without position restrictions, while the late group consisted of 235 patients who started ambulation after at least 3 days of bed rest and were limited to the prone position after surgery. In the early group, Prolene 6–0 was used as the dura suture material, while black silk 5–0 was used as the dura suture material in the late group. Results: : The overall incidence rate of CLC was 10.8%. Significant differences between the early and late groups were identified in the rate of CLC (2.5% vs. 13.6%), surgical repair required (1.3% vs. 7.7%), and length of hospital stay (2.99 vs. 9.29 days) (p<0.05). Logistic regression analysis revealed that CLC was associated with practices specific to the late group (p=0.011) and the revision surgery (p=0.022). Conclusion : Using Prolene 6–0 as a dura suture material for intradural spinal surgery resulted in lower CLC rates compared to black silk 5–0 sutures despite a shorter bed rest period. Our findings revealed that suture - needle ratio related to dura defect was the most critical factor for CLC. One-day ambulation after primary dura closure using Prolene 6–0 sutures appears to be a cost-effective and safe strategy for intradural spinal surgery.

Objective: Proper management of lymph nodes (LNs) with ultrasonographic (US) indeterminate features in thyroid cancerpatients remains elusive. We aimed to evaluate the malignancy risk and US findings predictive of malignancy for USindeterminate LNs in preoperative thyroid cancer patients through node-by-node correlation. Materials and Methods: A total of 348 LNs in 284 thyroid cancer patients, who underwent fine-needle aspiration or coreneedlebiopsy between December 2006 and June 2015, were included. We determined the malignancy risks for US probablybenign, indeterminate, and suspicious categories. For US indeterminate LNs, which had neither echogenic hilum nor hilarvascularity in the absence of any suspicious finding, US findings were compared between benign and metastatic LNs usingMann-Whitney U test and Fisher’s exact test. Results: US imaging diagnoses were probably benign in 20.7% (n = 72) cases, indeterminate in 23.6% (n = 82), andsuspicious in 55.7% (n = 194). Malignancy risk of US indeterminate LNs (19.5% [16/82]) differed from those of the USprobably benign (2.8% [2/72]) (p = 0.002) and US suspicious LNs (78.4% [152/194]) (p < 0.001). Among US indeterminate LNs,there were no significant differences in short, long, and long-to-short diameter (L/S) ratios between benign and metastatic LNs(3.9 vs. 3.8 mm, p = 0.619; 7.3 vs. 7.3 mm, p = 0.590; 1.9 vs. 1.9, p = 0.652). Conclusion US indeterminate LNs were frequently encountered during preoperative evaluation and had intermediate malignancyrisk. Given the lack of discriminative power of size criteria and L/S ratio, clinical factors such as surgical strategy and nodesize should be considered for proper triage of US indeterminate LNs in thyroid cancer.

Objective: To evaluate pharmacokinetic variables from contrast-enhancing lesions (CELs) and non-enhancing T2 high signal intensity lesions (NE-T2HSILs) on dynamic contrast-enhanced (DCE) magnetic resonance (MR) imaging for predicting progression-free survival (PFS) in glioblastoma (GBM) patients. Materials and Methods: Sixty-four GBM patients who had undergone preoperative DCE MR imaging and received standard treatment were retrospectively included. We analyzed the pharmacokinetic variables of the volume transfer constant (Ktrans) and volume fraction of extravascular extracellular space within the CEL and NE-T2HSIL of the entire tumor. Univariate and multivariate Cox regression analyses were performed using preoperative clinical characteristics, pharmacokinetic variables of DCE MR imaging, and postoperative molecular biomarkers to predict PFS. Results: The increased mean Ktrans of the CEL, increased 95th percentile Ktrans of the CELs, and absence of methylated O6- methylguanine-DNA methyltransferase promoter were relevant adverse variables for PFS in the univariate analysis (p = 0.041, p = 0.032, and p = 0.083, respectively). The Kaplan-Meier survival curves demonstrated that PFS was significantly shorter in patients with a mean Ktrans of the CEL > 0.068 and 95th percentile Ktrans of the CEL > 0.223 (log-rank p = 0.038 and p = 0.041, respectively). However, only mean Ktrans of the CEL was significantly associated with PFS (p = 0.024; hazard ratio, 553.08; 95% confidence interval, 2.27–134756.74) in the multivariate Cox proportional hazard analysis. None of the pharmacokinetic variables from NE-T2HSILs were significantly related to PFS. Conclusion Among the pharmacokinetic variables extracted from CELs and NE-T2HSILs on preoperative DCE MR imaging, the mean Ktrans of CELs exhibits potential as a useful imaging predictor of PFS in GBM patients.

Several 19alpha-hydroxyursane-type triterpenoids and hydrolysable tannins have beneficial effects on human health. Rubus crataegifolius (Rosaceae) has the cleft simple leaf whereas R. parvifolius has pinnate compound leaves. This research was aimed to find the variation in the contents of the triterpenoids and tannins between the infected versus uninfected leaves of R. coreanus and R. parvifolius and between young versus mature leaves. Triterpenoids and tannins were quantitatively analyzed by HPLC. Six triterpenoids including tormentic acid, euscaphic acid, 23-hydroxytormentic acid, coreanoside F1, kaji-ichigoside F1 and niga-ichigoside F1 were used for standard compounds. Gallotannins and ellagitannins were quantitatively evaluated using the indicatives of methyl gallate and ellagic acid. The infected leaves of R. crataegifolius contained higher levels of triterpenoids and tannin than the uninfected leaves; however, lower quantity of total tannin was observed in the mature leaves than in the young leaves. Although the pinnate compound leaves of R. parvifolius exhibited similar tendency of those compositional variation with R. crataegifolius each other, its contents of triterpenoids do not considerably vary. Variation of the contents of triterpenoids and tannins were particularly distinct in R. crataegifolius by growth and infection.
Chromatography, High Pressure Liquid ; Ellagic Acid ; Humans ; Hydrolyzable Tannins ; Rosaceae ; Tannins*

Rotavirus (RV) is one of the most important viral etiologic agents of acute gastroenteritis (AGE) in children. Although effective RV vaccines (RVVs) are now used worldwide, novel genotypes and outbreaks resulting from rare genotype combinations have emerged. This study documented RV genotypes in a Korean population of children with AGE 5 yr after the introduction of RVV and assessed potential genotype differences based on vaccination status or vaccine type. Children less than 5-yr-old diagnosed with AGE between October 2012 and September 2013 admitted to 9 medical institutions from 8 provinces in Korea were prospectively enrolled. Stool samples were tested for RV by enzyme immunoassay and genotyped by multiplex reverse-transcription polymerase chain reaction. In 346 patients, 114 (32.9%) were RV-positive. Among them, 87 (76.3%) patients were infected with RV alone. Eighty-six of 114 RV-positive stool samples were successfully genotyped, and their combinations of genotypes were G1P[8] (36, 41.9%), G2P[4] (12, 14.0%), and G3P[8] (6, 7.0%). RV was detected in 27.8% of patients in the vaccinated group and 39.8% in the unvaccinated group (P=0.035). Vaccination history was available for 67 of 86 cases with successfully genotyped RV-positive stool samples; RotaTeq (20, 29.9%), Rotarix (7, 10.4%), unvaccinated (40, 59.7%). The incidence of RV AGE is lower in the RV-vaccinated group compared to the unvaccinated group with no evidence of substitution with unusual genotype combinations.
Child, Preschool ; Feces/virology ; Gastroenteritis/immunology/prevention & control/virology ; Genotype ; Humans ; Infant ; *Mass Vaccination ; RNA, Viral/genetics ; Republic of Korea ; Reverse Transcriptase Polymerase Chain Reaction ; Rotavirus/*classification/*genetics/isolation & purification ; Rotavirus Infections/immunology/*prevention & control/virology ; Rotavirus Vaccines/*immunology ; Vaccines, Attenuated/immunology

PURPOSE: This study aimed to evaluate the disease severity of children suffering from gastroenteritis using different scales. The results are compared and subsequently classified on the basis of the type of virus causing the disease in order to investigate the differences in clinical characteristics and disease severity according to pathogen. METHOD: This study was conducted prospectively with patients under 5 years of age diagnosed with acute gastroenteritis and hospitalized at 9 medical institutions in 8 regions across the Republic of Korea. Disease severity was evaluated using the Vesikari Scale, the Clark Scale, and the modified Flores Scale. Fecal samples collected from patients were used to detect rotavirus and enteric adenovirus by enzyme immunoassay, and for RT-PCR of norovirus, astrovirus, and sapovirus. RESULTS: There were a total of 214 patients with a male : female ratio of 1.58 : 1, of which 35 were under the age of 6 months (16.4%), 105 were aged 6-23 months (49.1%), and 74 were aged 24-59 months (34.5%). The rate of concordance between the Vesikari and Clark Scales was 0.521 (P<0.001) and, in severe cases, the Vesikari Scale was 60.7% and Clark Scale was 2.3%, indicating that the Clark Scale was stricter in the evaluation of severe cases. CONCLUSIONS: In children with gastroenteritis, there were differences in disease severity based on the scale used. Therefore, to achieve consistent results among researchers, either only a single scale or a measure of all scales should be used to determine disease severity.
Adenoviridae ; Child* ; Female ; Gastroenteritis* ; Humans ; Immunoenzyme Techniques ; Male ; Norovirus ; Prospective Studies ; Republic of Korea ; Rotavirus ; Sapovirus ; Weights and Measures*

DNA methylation may regulate gene expression by restricting the access of transcription factors. We have previously demonstrated that GATA-1 regulates the transcription of the CCR3 gene by dynamically interacting with both positively and negatively acting GATA elements of high affinity binding in the proximal promoter region including exon 1. Exon 1 has three CpG sites, two of which are positioned at the negatively acting GATA elements. We hypothesized that the methylation of these two CpGs sites might preclude GATA-1 binding to the negatively acting GATA elements and, as a result, increase the availability of GATA-1 to the positively acting GATA element, thereby contributing to an increase in GATA-1-mediated transcription of the gene. To this end, we determined the methylation of the three CpG sites by bisulfate pyrosequencing in peripheral blood eosinophils, cord blood (CB)-derived eosinophils, PBMCs, and cell lines that vary in CCR3 mRNA expression. Our results demonstrated that methylation of CpG sites at the negatively acting GATA elements severely reduced GATA-1 binding and augmented transcription activity in vitro. In agreement, methylation of these CpG sites positively correlated with CCR3 mRNA expression in the primary cells and cell lines examined. Interestingly, methylation patterns of these three CpG sites in CB-derived eosinophils mostly resembled those in peripheral blood eosinophils. These results suggest that methylation of CpG sites at the GATA elements in the regulatory regions fine-tunes CCR3 transcription.
Binding Sites ; Cell Line ; *CpG Islands ; DNA Methylation ; Enhancer Elements, Genetic ; Eosinophils/cytology/*metabolism ; Exons ; Fetal Blood/cytology/metabolism ; GATA1 Transcription Factor/*genetics/metabolism ; Gene Expression Regulation ; Humans ; Promoter Regions, Genetic ; RNA, Messenger/metabolism ; Receptors, CCR3/*genetics/metabolism ; Sequence Analysis, DNA ; *Transcription, Genetic