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Abstract Background Epilepsy, a chronic brain disorder characterized by abnormal brain activity that causes seizures and other symptoms, is typically treated using anti-epileptic drugs (AEDs) as the first-line therapy. However, due to the variations in their modes of action, identification of effective AEDs often relies on ad hoc trials, which is particularly challenging for pediatric patients. Thus, there is significant value in computational methods capable of assisting in the selection of AEDs, aiming to minimize unnecessary medication and improve treatment efficacy. Results In this study, we collected 7,507 medical records from 1,000 pediatric epilepsy patients and developed a computational clinical decision-supporting system for AED selection. This system leverages three multi-channel convolutional neural network (CNN) models tailored to three specific AEDs (vigabatrin, prednisolone, and clobazam). Each CNN model predicts whether a respective AED is effective on a given patient or not. The CNN models showed AUROCs of 0.90, 0.80, and 0.92 in 10-fold cross-validation, respectively. Evaluation on a hold-out test dataset further revealed positive predictive values (PPVs) of 0.92, 0.97, and 0.91 for the three respective CNN models, representing that suggested AEDs by our models would be effective in controlling epilepsy with a high accuracy and thereby reducing unnecessary medications for pediatric patients. Conclusion Our CNN models in the system demonstrated high PPVs for the three AEDs, which signifies the potential of our approach to support the clinical decision-making by assisting doctors in recommending effective AEDs within the three AEDs for patients based on their medical history. This would result in a reduction in the number of unnecessary ad hoc attempts to find an effective AED for pediatric epilepsy patients.

Abstract Background Elderly residents with physical and cognitive impairments in long-term care facilities are vulnerable to safety risks. Purpose This study investigated factors that influence patient safety cultures in delirium nursing care in long-term care facilities. Methods A cross-sectional survey was conducted among 214 nurses working in 12 long-term care facilities using a structured questionnaire from February 15, 2022, to March 14, 2022. Data analysis was performed using Pearson’s correlation coefficients and hierarchical analysis with SPSS/WIN 25.0 software. Results Significant factors associated with patient safety culture were identified. Organizational factors included the availability of delirium care manuals, nursing education and experience in delirium care, and the perceived necessity of delirium education. Individual factors included nurse-to-patient ratios, and nurses marital status. Conclusion To foster a strong patient safety culture, attention should be given to the availability of delirium care resources, the promotion of specialized and ongoing education and experience, and adequate staffing levels.

Abstract An ideal hydrogel for stem cell therapy would be injectable and efficiently promote stem cell proliferation and differentiation in body. Herein, an injectable, single‐component hydrogel with hyaluronic acid (HA) modified with phenylboronic acid (PBA) and spermidine (SM) is introduced. The resulting HAps (HA‐PBA‐SM) hydrogel is based on the reversible crosslinking between the diol and the ionized PBA, which is stabilized by the SM. It has a shear‐thinning property, enabling its injection through a syringe to form a stable hydrogel inside the body. In addition, HAps hydrogel undergoes a post‐injection “self‐curing,” which stiffens the hydrogel over time. This property allows the HAps hydrogel to meet the physical requirements for stem cell therapy in rigid tissues, such as bone, while maintaining injectability. The hydrogel enabled favorable proliferation of human mesenchymal stem cells (hMSCs) and promoted their differentiation and mineralization. After the injection of hMSCs‐containing HAps into a rat femoral defect model, efficient osteogenic differentiation of hMSCs and bone regeneration is observed. The study demonstrates that simple cationic modification of PBA‐based hydrogel enabled efficient gelation with shear‐thinning and self‐curing properties, and it would be highly useful for stem cell therapy and in vivo bone regeneration.

Background: Abnormal new bone formation can occur not only in the vertebral body but also can occur in facet, costovertebral, and costotransverse joints in radiographic axial spondyloarthritis (r-axSpA) patients. Little is known about the association between syndesmophyte progression and paravertebral joint ankylosis in r-axSpA. Objectives: Costotransverse joint ankylosis in r-axSpA patients was measured. Furthermore, the association between syndesmophyte progression for 2 years assessed by computed tomography syndesmophyte score (CTSS) and facet, costovertebral, and costotransverse joints ankylosis were evaluated. Design: Single-center, prospective, cohort study. Methods: Whole spine CT images taken at baseline and 2-year follow-up were used to calculate the CTSS of the vertebral body. In addition, ankylosis of the facet/costovertebral/costotransverse joints was scored. CTSS (range, 0–552) and facet joint ankylosis (range, 0–46) were assessed at 23 vertebral units. Costovertebral joints at T1–T12 (range, 0–48) and costotransverse joints at T1–T10 (range, 0–20) were also assessed by independent two readers. Intraclass correlation coefficients (ICC) were calculated to determine inter-reader reliability. Odds ratios (OR) were calculated to identify the associations between syndesmophyte progression and the baseline status of facet, costovertebral, and costotransverse joints. Results: In all, 50 patients with r-axSpA were included. Readers 1 and 2 identified C7–T3 (facet joints), T5–T7 and T12 (costovertebral joints), and T8–T9 (costotransverse joints), as common sites of ankylosis at baseline and at 2-year follow-up. The ICCs for the facet, costovertebral, and costotransverse joints at baseline were 0.876, 0.952, and 0.753, respectively. OR of baseline costovertebral and costotransverse joint ankylosis for predicting syndesmophyte progression of the vertebral body was 4.644 [95% confidence interval (CI), 2.295–9.398] and 1.524 (95% CI, 1.036–2.244), respectively. Conclusion: Costotransverse joint ankylosis in r-axSpA patients can be measured semi-quantitatively on whole spine CT, and ankylosis of the costotransverse and costovertebral joints predicts the progression of syndesmophytes. Trial registration: Not applicable.

Abstract This study determined the 24-month outcomes of perampanel treatment in children and adolescents with epilepsy. The percentage of ≥ 50% responders was 47.3% (139/294) at 12 months and 49.0% (144/294) at 24 months. A 100% reduction in seizures for more than 12 months was observed in 12.2% (36/294). Discontinuation occurred in 39.8% (117/294). The most common reason for discontinuation was adverse events (29.1%, 34/117). Baseline seizure frequency was higher in children aged

Extensive research has been conducted on the in vitro mass propagation of pear (Pyrus spp.) trees through vegetative propagation, demonstrating high efficiency in shoot multiplication across various pear species. However, the low in vitro rooting rates remain a significant barrier to the practical application and commercialization of mass propagation. This study aims to determine the favorable conditions for inducing root formation in the in vitro microshoots of Pyrus genotypes. The base of the microshoots was exposed to a high concentration (2 mg L−1) of auxins (a combination of IBA and NAA) for initial root induction at the moment when callus formation begins. The microshoots were then transferred to an R1 medium (1/2 MS with 30 g L−1 sucrose without PGRs) to promote root development. This method successfully induced rooting in three European pear varieties, one Asian pear variety, and a European–Asian hybrid, resulting in rooting rates of 66.7%, 87.2%, and 100% for the European pear (P. communis), 60% for the Asian pear (P. pyrifolia), and 83.3% for the hybrid pear (P. pyrifolia × P. communis) with an average of 25 days. In contrast, the control group (MS medium) exhibited rooting rates of 0–13.3% after 60 days of culture. These findings will enhance in vitro root induction for various pear varieties and support the mass propagation and acclimatization of pear. The in vitro root induction method developed in this study has the potential for global commercial application in pear cultivation.

Background: Interstitial lung disease (ILD) is a critical extra-articular manifestation of rheumatoid arthritis (RA). However, little is known about the risk factors of RA-ILD. Objectives: Here, we examined the effect of demographic, clinical, therapeutic, and environmental factors on the incidence of ILD in RA patients using the Korean College of Rheumatology Biologics and Targeted Therapy (KOBIO) registry. Design: We used data from the KOBIO registry, a multi-center, prospective, observational cohort that included RA patients in South Korea. Methods: RA patients who used biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) or conventional synthetic (cs)DMARDs, and were enrolled in the KOBIO registry, were examined. Demographic, clinical, and radiographic characteristics, as well as medications, were recorded at baseline and annually thereafter. Kaplan–Meier curves and the log-rank test were used to compare the incidence of ILD between RA patients taking different b/tsDMARDs. Hazard ratios (HRs) were calculated by Cox regression analyses. Results: In total, 2492 patients (1967 in the b/tsDMARDs group and 525 in the csDMARDs group) were analyzed. The b/tsDMARDs group showed longer disease duration, higher erythrocyte sedimentation rate/C-reactive protein, and higher disease activity score-28 (DAS28) than the csDMARDs group. The incidence of ILD was significantly higher in those taking tumor necrosis factor inhibitors and abatacept than in those taking csDMARDs (log ranked p

Purpose Lamotrigine (LTG) is often used as adjunctive therapy in Lennox-Gastaut syndrome (LGS); however, it may worsen myoclonic and atypical absence seizures in LGS patients. This study reviewed the overall efficacy and safety of LTG in children with LGS. Methods This retrospective study included 38 patients (aged 50% in 47.4% of patients (18/38). After 6 months, 20 patients (20/36, 55.6%) showed a favorable response. After 12 months, five patients (5/11, 45.5%) responded to treatment. Three patients showed myoclonic seizures at the start of treatment and >50% amelioration in seizure frequency at the 3- and 6-month follow-up visits. Conclusion This study reaffirms the efficacy and safety of LTG in children with LGS. Therefore, LTG is strongly recommended as an adjunctive therapy for children with LGS.

Background: Everolimus is an inhibitor of mammalian target of rapamycin complex 1. As mutations in TSC1 and TSC2, which cause partial-onset seizures associated with TSC, were found in focal cortical dysplasia type Ⅱ (FCD Ⅱ) patients, a clinical trial has been performed to explore the efficacy and safety of everolimus in FCD patients. However, no dosage regimen was determined to treat FCD II. To recommend an optimal dose regimen for FCD patients, a population pharmacokinetic model of everolimus in FCD patients was developed.Methods: The data of everolimus were collected from September 2017 to May 2020 in a tertiary-level hospital in Korea. The model was developed using NONMEM® software version 7.4.1 (Icon Development Solutions, Ellicott City, MD, United States).Results: The population pharmacokinetics of everolimus was described as the one-compartment model with first-order absorption, with the effect of BSA on clearance. The final model was built as follows: TVCL = 12.5 + 9.71 × (BSA/1.5), TVV = 293, and TVKA = 0.585. As a result of simulation, a dose higher than 7 mg/m2 is needed in patients with BSA 0.5 m2, and a dose higher than 6 mg/m2 is needed in patients with BSA 0.7 m2. A dose of 4.5 mg/m2 is enough in the population with BSA higher than 1.5 m2 to meet the target trough range of 5–15 ng/mL.Conclusion: Based on the developed pharmacokinetics model, the optimal dose of everolimus in practice was recommended by considering the available strengths of Afinitor disperz®, 2 mg, 3 mg, and 5 mg.

ObjectiveTo investigate the quantitative electroencephalography (EEG) features associated with a high risk of sudden unexpected death in epilepsy (SUDEP) in patients with Dravet syndrome (DS).MethodsPatients with DS and healthy controls (HCs) who underwent EEG were included in the study. EEG signals were recorded using a 21 channel digital EEG system, and pre-processed data were analyzed to identify quantitative EEG features associated with a high SUDEP risk. To assess the risk of SUDEP, SUDEP-7 scores were used.ResultsA total of 64 patients with DS [38 males and 26 females, aged: 128.51 ± 75.50 months (range: 23–380 months)], and 13 HCs [7 males and 6 females, aged: 95.46 ± 86.48 months (range: 13–263 months)] were included. For the absolute band power, the theta power was significantly higher in the high-SUDEP group than in the low-SUDEP group in the central brain region. For the relative band power, the theta power was also significantly higher in the high-SUDEP group than in the low-SUDEP group in the central and occipital brain regions. The alpha power was significantly lower in the high-SUDEP group than in the low-SUDEP group in the central and parietal brain regions.ConclusionPatients with high SUDEP-7 scores have different EEG features from those with low SUDEP-7 scores, suggesting that EEG may be used as a biomarker of SUDEP in DS.SignificanceEarly intervention in patients with DS at a high risk of SUDEP can reduce mortality and morbidity. Patients with high theta band powers warrant high-level supervision.

Abstract The CT syndesmophyte score (CTSS) can evaluate spinal progression more precisely than mSASSS in ankylosing spondylitis (AS); however, it is complex and time consuming. Here, we propose a simplified CTSS (sCTSS) for measuring spinal structural changes in AS. Patients with AS were recruited from a single tertiary hospital. Baseline and 2-year follow-up whole spine CT images were used to calculate CTSS and sCTSS. The sCTSS used the anterior and posterior vertebral corners, and ranged 0–184. Intraclass correlation coefficients (ICC) were calculated, as well as the smallest detectable changes. Fifty AS patients were included. For reader 1, the mean sCTSS at baseline and 2-year follow-up were 11.7 ± 14.6 and 15.8 ± 16.1, whereas those for reader 2 were 12.0 ± 12.5 and 15.8 ± 15.7, respectively. The ICCs for CTSS at baseline and at 2-year follow-up were 0.97 (95% confidence interval [CI] 0.96–0.99) and 0.98 (0.97–0.99), respectively, and that for changes over the 2 years was 0.48 (95% CI 0.23–0.67). For sCTSS, the ICCs were 0.96 (95% CI 0.92–0.97), 0.97 (95% CI 0.94–0.98), and 0.58 (95% CI 0.36–0.74), respectively. Detection rates for syndesmophyte progression were comparable between CTSS and sCTSS. The detection rate for syndesmophytes on only lateral side was 13.2 and 11.4%, and 11.4 and 15.2% at baseline and 2-year follow-up (reader 1 and 2). sCTSS and CTSS showed similar detection rates for syndesmophyte progression. sCTSS may be a reliable method for evaluating spinal structural damage in AS.

Abstract The present study evaluated the predictive role of baseline radiographic change and disease activity on drug retention and clinical response in patients with rheumatoid arthritis (RA) treated with tumor necrosis factor inhibitor (TNFi). Korean Observational Study Network for Arthritis (KORONA) registry was evaluated to identify RA patients treated with a TNFi. Disease activity score-28 (DAS28) was evaluated at baseline and 1 year after TNFi initiation or at termination of TNFi due to inefficacy (within 1 year). The retention rate of TNFi was compared in patients with and without bony erosions. The hazard ratio (HR) for drug retention was evaluated by Cox regression analysis, as was the odds ratio (OR) for achieving remission (DAS28

Purpose Developmental and/or epileptic encephalopathy with spike-and-wave activation in sleep (D/EE-SWAS) is a spectrum of conditions characterized by various phenotypes of cognitive, linguistic, and behavioral regression associated with spike-and-wave activation in sleep. We aimed to investigate the phenotypic spectrum and treatment outcomes of pediatric patients with D/EE-SWAS. Methods We retrospectively analyzed the medical records of pediatric patients diagnosed with D/EE-SWAS and treated at Severance Children’s Hospital from 2006 to 2022. We extracted information from their medical records on electroencephalography before and after treatment, types of treatment, seizure frequency, and developmental profiles. The primary outcome was reduction of the spike-wave index on electroencephalography after treatment. Results Twenty-one patients with a median age of 5.3 years (interquartile range, 4.1 to 6.6) at diagnosis were included. Ten patients had delayed development. The patients received various anti-seizure medications. Fourteen received long-term, high-dose steroid therapy, 10 were placed on a ketogenic diet, four received intravenous steroid pulse therapy, and one each was treated with intravenous immunoglobulin and cannabidiol. The most effective treatments were steroid therapy and a ketogenic diet, which were also effective in reducing seizures and improving cognition. Side effects during treatment were transient and treatable. Conclusion We described the clinical spectrum of pediatric patients with D/EE-SWAS. Steroid therapy and a ketogenic diet can be considered effective therapeutic options for patients with D/EE SWAS.

Purpose This study presents the characteristics of patients with mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) with SLC35A2 somatic variants in the brain who underwent epilepsy surgery and showed clinical improvement in seizures. Methods We collected 10 patients with SLC35A2 somatic mutations in the brain who underwent surgery to treat drug-resistant epilepsy at Severance Children’s Hospital from 2014 to 2019 and retrospectively reviewed their genetic profiles, neuropathologic results, clinical features, pre-operative evaluations, and post-operative outcomes. Results Six of the 10 patients with SCL35A2 somatic mutations in the brain had Lennox Gastaut syndrome (LGS) evolving from infantile spasms (IS), three had LGS, and one had IS. The median value of variant allele frequencies (VAFs) was 5.7% (1.7% to 5.8%; range, 1.4% to 22.9%). Nonsense mutations were the most common (50%), followed by missense mutations (40%) and a splicing site mutation (10%). Eight patients (80%) had good post-operative outcomes, with freedom from disabling seizures in five (Engel class I) and rare disabling seizures in three (Engel class II). Four of the eight patients who could be assessed for social quotient (SQ) after surgery showed SQ improvements by 12.2±6.4. Although all patients were finally diagnosed with MOGHE, seven (70%) were initially diagnosed with gliosis, two with mild malformation of cortical development, and one with no abnormality. Conclusion All patients with SCL35A2 brain somatic mutations, even with low VAFs, had refractory epilepsy such as LGS or IS, and were finally diagnosed with MOGHE. This report is the first in Korea to our knowledge.

Abstract Herein, we investigated the effect of DJ-1 on helper T cell differentiation, fibroblast-like synoviocyte (FLS) activation, and osteoclastogenesis in rheumatoid arthritis (RA). Serum and synovial fluid (SF) of RA and osteoarthritis (OA) patients were collected, and DJ-1 and H2O2 levels were investigated. CD4+ cells from peripheral blood mononuclear cells (PBMCs) were cultured under type 17 helper T cell (Th17) polarization conditions, and CD4+ T cell differentiation, pro-inflammatory cytokine levels, and soluble receptor activator of nuclear factor kappa-Β ligand (RANKL) were assessed. RA-FLSs were stimulated with 50 μM H2O2, and DJ-1 (10, 50, 100 ng/mL) to evaluate MMP-9, VEGF, TNF-α, and sRANKL production, while RANKL+ FLSs were assessed using flow cytometry. Monocytes were cultured with RANKL or IL-17A with or without DJ-1 and H2O2-pretreated RA-FLS, and tartrate-resistant acid phosphatase (TRAP) staining and RT-qPCR of osteoclast-related genes were performed. The levels of DJ-1 and H2O2 in serum and SF of RA patients were higher than those of OA patients. Under Th17-polarizing conditions, CD4+RANKL+ and CD4+CCR4+CCR6+CXCR3- T cells decreased, whereas CD4+CD25highFoxp3+ T cell increased after DJ-1 administration. Additionally, IL-17A, TNF-α, and sRANKL levels decreased in DJ-1-treated groups. DJ-1 lowered MMP-9, VEGF, TNF-α, and sRANKL levels, and RANKL+ FLS in ROS-stimulated RA-FLS. Both RANKL and IL-17A stimulated osteoclast differentiation, DJ-1 decreased TRAP+ cell count, and the expression levels of TRAP, ATP6v0d2, NFATc1, and CTSK. These findings were also observed in in vitro osteoclastogenesis with DJ-1 pretreated RA-FLS. As DJ-1 regulates Th17/Treg imbalance, pro-inflammatory cytokine production, RA-FLS activation, and osteoclastogenesis, it holds potential for RA therapy.

OBJECTIVES This study investigated whether Janus kinase inhibitors (JAKis) raise the risk of cardiovascular disease (CVD), venous thromboembolism (VTE), and cancer in patients with rheumatoid arthritis (RA). METHODS We conducted a real-world retrospective observational study using data obtained from the Korean National Health Insurance Service database. Two data sets were analyzed: tumor necrosis factor inhibitor (TNFi)/JAKi-naive RA patients (set 1) and all RA patients who used TNFis or JAKis (set 2). The incidence rate ratios (IRRs) and hazard ratios (HRs) for acute myocardial infarction (AMI), stroke, cardiovascular (CV)-related mortality, major adverse cardiovascular events (MACE), VTE, arterial thromboembolism (ATE), cancer, and all-cause mortality were compared between the JAKi and TNFi groups. RESULTS Set 1 included 1,596 RA patients (JAKi group: 645; TNFi group: 951), and set 2 included 11,765 RA patients (JAKi group: 2,498; TNFi group: 9,267). No adverse events (AEs) showed significantly higher IRRs in the JAKi groups than in the TNFi groups of sets 1 and 2. The HRs for MACE in the JAKi groups of sets 1 and 2 were 0.59 (95% confidence [CI], 0.35 to 0.99) and 0.80 (95% CI, 0.67 to 0.97), respectively. The JAKi group of set 2 showed a significantly higher risk of all-cause mortality (HR, 1.71; 95% CI, 1.32 to 2.20), but the other AEs did not demonstrate increased risks in the JAKi groups. CONCLUSIONS In this study, JAKis did not increase the risk of AMI, stroke, CV-related mortality, MACE, VTE, ATE, or cancer in Korean RA patients relative to TNFis.

Apple (Malus domestica (Suckow) Borkh., 1803) is economically important horticultural fruit crop in the world. In this study, the complete chloroplast genome of Korean apple cultivar ‘Kamhong’ was characterized through the de novo assembly of Illumina sequencing data. The chloroplast genome is a circular molecule of 161,069 bp length with 36.55% GC content and has a total of 112 genes including 78 protein-coding genes, 30 transfer RNA genes, and 4 ribosomal RNA genes. Phylogenetic analysis with protein-coding sequences of chloroplast genome revealed that ‘Kamhong’ was closely grouped with M. domestica cultivars reported in China. The genomic data generated in this study can extend a molecular basis for phylogenetic relationships of Korean cultivar ‘Kamhong’ with other M. domestica cultivars bred in other countries.

Prunus Linnaeus 1753 species include many economically important fruit crops, of which plumcot is generated by inter-species crossing between Prunus salicina Lindley 1830 × Prunus armeniaca Linnaeus 1753. In this study, the complete chloroplast genome of Korean plumcot cultivar ‘Harmony’ was characterized through the de novo assembly of Nanopore and Illumina sequencing data. The chloroplast genome is a circular molecule of 157,916 bp length with 36.75% GC content and has a total of 113 genes including 79 protein-coding genes, 30 transfer RNA genes, and four ribosomal RNA genes. Phylogenetic analysis with protein-coding sequences of chloroplast genome revealed that ‘Harmony’ showed closer to P. salicina than P. armeniaca.

Abstract Rheumatoid arthritis (RA) is a systemic inflammatory arthritis in which primary prevention is key. However, the impact of lifestyle and comorbidities on RA development is unknown. Data from the Korean National Health Insurance Service (NHIS)-national sample cohort from 2002 to 2016 were used. At baseline, demographic characteristics, socioeconomic status, type of residential area, lifestyle behaviours (including exercise), and comorbidities (including the Charlson Comorbidity Index, CCI) were included. Cox regression analysis and Kaplan–Meier curves were used to evaluate the impact of lifestyle and comorbidities on seropositive RA occurrence. A total of 517,053 participants were included in the analysis for seropositive RA occurrence. Mean follow up duration was 71.5 and 142.3 person-month for seropositive RA occurrence group and non-occurrence group, respectively. Seropositive RA was diagnosed in 1,948 participants (0.37%) during follow-up. Cox regression analysis revealed that being aged between 40 and 79, a higher CCI, and hyperlipidemia resulted in elevated hazard ratios (HRs) for seropositive RA, whereas male gender, city residence, moderate alcohol consumption, high regular exercise and a BMI between 23 and 34.9 kg/m2 resulted in lower HRs. Using Korean NHIS data, the present study demonstrates that high-intensity regular physical exercise and moderate alcohol consumption are negatively associated with seropositive RA occurrence, which are modifiable lifestyle habits that might aid the primary prevention of seropositive RA.

BackgroundTrio test has been widely used for diagnosis of various hereditary disorders. We aimed to investigate the contribution of trio test in genetically diagnosing neurodevelopmental disorders (NDD).MethodsWe retrospectively reviewed 2,059 NDD cases with genetic test results. The trio test was conducted in 563 cases. Clinical usefulness, optimal timing, and methods for the trio test were reviewed.ResultsPathogenic or likely pathogenic variants were detected in 112 of 563 (19.9%) patients who underwent the trio test. With trio test results, the overall diagnostic yield increased by 5.4% (112/2,059). Of 165 de novo variants detected, 149 were pathogenic and we detected 85 novel pathogenic variants. Pathogenic, de novo variants were frequently detected in CDKL5, ATP1A3, and STXBP1.ConclusionThe trio test is an efficient method for genetically diagnosing NDD. We identified specific situations where a certain trio test is more appropriate, thereby providing a guide for clinicians when confronted with variants of unknown significance of specific genes.

BackgroundMechanical stress are one of the pathogenesis of axial spondyloarthritis (axSpA). During pregnancy, the mechanical overload on the spine and pelvis increases due to gravid uterus. We aimed to investigate whether pregnancy affects radiographic progression in patients with radiographic axSpA (r-axSpA) based on computed tomography (CT) evaluations.Materials and methodsThis retrospective study included women with r-axSpA aged 19–49 years who underwent at least two CT evaluations of the whole spine and/or sacroiliac joints (SIJs) at intervals of 2–4 years. To compare radiographic progression after delivery, we classified the patients into two groups: delivery group and controls. The delivery group was restricted to women who had the first CT ∼2 years before delivery and the second CT ∼2 years after delivery. The CT Syndesmophyte Score (CTSS) (0–522) and SIJ scores (0–40) were used to evaluate spinal syndesmophytes and erosion, joint space narrowing, and sclerosis of the SIJs.ResultsA total of 21 women in the delivery group and 38 women in the control group were included. The median (Q1–Q3) CTSS at baseline in the delivery group and controls was 19 (16–23) and 20 (13.25–27.75), and the median progression was 1 (0–3) and 0 (0–1) during the median 2.9-year follow-up, respectively. The median (Q1–Q3) SIJ score at baseline in the delivery group and controls was 13 (8–22) and 11 (6–22), and the median progression was 1.5 (0–3) and 1 (0–2), respectively. Using cut-off 0.5, 52.9, and 61.9% of r-axSpA patients and 39.3 and 44.4% of controls showed progression of whole spine and SIJs, respectively. However, no difference in proportion of spinal and SIJ progression and absolute score changes per time point was observed between two groups. Moreover, the SIJ score changes were comparable according to the delivery method.ConclusionPregnancy and delivery do not affect the radiographic progression of the spine and SIJs in women with r-axSpA assessed by CT.

Abstract The clinical data on the biologic disease-modifying antirheumatic drug (bDMARD) use in late-onset ankylosing spondylitis (LOAS) is limited. Thus, this study aimed to evaluate the drug efficacy and retention rate of bDMARDs in LOAS and compare it to young-onset ankylosing spondylitis (YOAS). Data of patients with AS receiving bDMARDs were extracted from the Korean College of Rheumatology Biologics and Targeted Therapy registry. Patients whose age of onset was > 50 years and ≤ 50 years were classified as having LOAS and YOAS, respectively. Their baseline characteristics and disease-associated parameters were evaluated. Drug efficacy [Ankylosing Spondylitis Disease Activity Score (ASDAS)-clinically important improvement (CII), ASDAS-major improvement (MI), Assessment of SpondyloArthritis International Society (ASAS) 20, and ASAS 40] at 1-year follow-up and drug retention rates were assessed. A total of 1708 patients (comprising 1472 patients with YOAS and 236 patients with LOAS) were included in this analysis. The LOAS group had a lower prevalence among males, lower HLA-B27 positivity and a higher prevalence of peripheral arthritis. Patients with LOAS were more likely to have higher disease-associated parameters (inflammatory reactants, patient global assessment, ASDAS-erythrocyte sedimentation rate, and ASDAS-C-reactive protein). LOAS was negatively associated with achieving ASDAS-CII, ASAS 20, and ASAS 40. The drug retention rate was lower in LOAS; however, the propensity score-matched and covariate-adjusted hazard ratios for bDMARD discontinuation were comparable to YOAS. There were no differences in the drug retention rates based on the type of bDMARD used in LOAS. Inferior clinical efficacy and shorter drug retention time were found in patients with LOAS receiving bDMARDs using real-world nationwide data. There were no differences among each bDMARD type.

BackgroundKetogenic dietary therapy (KDT) is used as an effective treatment for epilepsy. However, KDT carries the risk of bone health deterioration; therefore, vitamin D supplementation is required. Vitamin D replacement therapy in KDT has not been established because it may be related to hypercalciuria/urolithiasis, which are common adverse effects of KDT. Hence, this study aimed to evaluate the dose-dependent association between vitamin D3 and hypercalciuria/urolithiasis in patients undergoing KDT and dose optimization for renal complications.Materials and methodsOverall, 140 patients with intractable childhood epilepsy started 3:1 KDT (lipid to non-lipid ratio) at the Severance Children’s Hospital from January 2016 to December 2019. Regular visits were recommended after KDT initiation. Participants were assessed for height, weight, serum 25-hydroxyvitamin D (25-OH-D3) level, parathyroid hormone level, and ratio of urinary excretion of calcium and creatinine (Uca/Ucr). Kidney sonography was conducted annually. Patients who already had urolithiasis and were taking hydrochlorothiazide before KDT, failed to maintain KDT for 3 months, did not visit the pediatric endocrine department regularly, did not take prescribed calcium and vitamin D3 properly, or needed hospitalization for > 1°month because of serious medical illness were excluded. Data from patients who started diuretic agents, e.g., hydrochlorothiazide, were excluded from that point because the excretion of calcium in the urine may be altered in these patients.ResultIn total, 49 patients were included in this study. Uca/Ucr ratio significantly decreased with increasing levels of 25-OH-D3 (p = 0.027). The odds ratio for hypercalciuria was 0.945 (95% confidence interval, 0.912–0.979; p = 0.002) per 1.0 ng/mL increment in 25-OH-D3 level. Based on findings of receiver operating characteristic curve analysis and Youden’s J statistic, the cut-off 25-OH-D3 level for preventing hypercalciuria was > 39.1 ng/mL at 6 months. Furthermore, the vitamin D3 supplementation dose cut-off was > 49.5 IU/kg for hypercalciuria prevention.ConclusionAn inverse relationship between Uca/Ucr ratio and 25-OH-D3 level was noted, which means that vitamin D supplementation is helpful for preventing hypercalciuria related to KDT. We suggest that the recommended 25-OH-D3 level is > 40 ng/mL for hypercalciuria prevention and that KDT for children with epilepsy can be optimized by vitamin D3 supplementation at 50 IU/kg.

Abstract Background Cardiovascular diseases (CVDs) are the leading cause of death in patients with rheumatoid arthritis (RA). Coronary artery calcium (CAC) score quantifies the severity of atherosclerosis. We estimated CVD risk using several methods and compared these with the CAC score to identify the most suitable CVD risk calculator in RA patients. Methods We recruited RA patients, and the 10-year CVD risk was assessed using various tools, viz. Framingham risk score, Systemic Coronary Risk Evaluation (SCORE), Atherosclerotic Cardiovascular Disease (ASCVD) risk estimator plus, QRISK3, Expanded Risk Score in Rheumatoid Arthritis (ERS-RA), and Reynolds risk score. Computed tomography was used to determine the CAC score of each patient. Correlation analysis and linear regression analysis between the CAC score and CVD risk score was performed. Results In total, 54 RA patients were enrolled. ERS-RA showed the highest correlation coefficient (r = 0.430, P = 0.001). In multivariate linear regression analysis, ERS-RA (β = 10.01, 95% confidence interval 3.78–16.23) showed a positive association with the CAC score in RA patients. Conclusions The ERS-RA method was highly correlated with the CAC score in RA patients. Therefore, the application of the ERS-RA method may be suitable for predicting subclinical atherosclerosis and CVD risk in RA patients.

We explored the correlation between extracellular matrix (ECM) components and spontaneous abortion by defining the types and levels of ECM proteins that are transcriptionally and translationally expressed in endometrial stromal (ES) cells. The ES cells were retrieved from the uterus of a woman who had experienced normal delivery without spontaneous abortion and one who had experienced spontaneous abortion. In the presence and absence of spontaneous abortion, the transcription of eight ECM protein-encoding genes [fibronectin, nidogen-1, tenascin C, vitronectin, elastin, collagen type 1 alpha 1 chain (COL1A1), COL3A1, and COL5A2] was observed, whereas four ECM protein-encoding genes (laminin, COL2A1, COL4A3, and COL11A1) were not transcribed. Translation of all ECM protein-encoding genes was equally observed on the surface of ES cells derived from women with normal pregnancy and spontaneous abortion; however, the proportion of ES cells expressing each ECM protein and the quantity of each ECM protein expressed on the cell surface were significantly different. These results demonstrate that altered expression of ECM proteins in ES cells constituting the endometrium may be a key factor in triggering spontaneous abortion.

Purpose We aimed to assess the efficacy and safety of lacosamide in Korean adolescents with Lennox-Gastaut syndrome (LGS), especially in those who concomitantly used other sodium channel blockers (SCBs). Methods We retrospectively reviewed the medical records of adolescents with LGS who initiated lacosamide from ages 16 to 18. The efficacy of lacosamide was evaluated by seizure frequency before and after lacosamide trial. Safety was assessed by lacosamide-related adverse events, consequent dosage titration, and titration effects. We compared the efficacy and safety of lacosamide according to concomitant use of other SCBs. Results In 26 eligible adolescents with LGS, the median age of seizure onset was 2.0 years, and the median age of lacosamide initiation was 17.1 years. At the time of lacosamide initiation, the median number of concomitant antiepileptic drugs was 4, and 23 patients (88%) had tried dietary, surgical, or neuromodulatory therapies. Patients were on lacosamide for a median of 13.5 months with a median maximal dosage of 8.1 kg/mg/day. After lacosamide trial, 11 patients (42%) had an over 50% reduction of seizures. Six patients (23%) had lacosamide-related adverse events. The percentage of patients on concomitant SCBs was higher among non-responders (10 of 15, 67%) than among responders (6 of 11, 55%). Patients taking concomitant SCBs had a higher ratio of adverse effects (5 of 16, 31%) than their counterparts (1 of 10, 10%). Conclusion Lacosamide is an effective and tolerable antiepileptic drug in adolescents with LGS. Concomitant SCB use may lead to less effective treatment and more adverse events.

Approximately 50 million people have epilepsy worldwide. Prognosis may vary among patients depending on their seizure semiology, age of onset, seizure onset location, and features of electroencephalogram (EEG). Several researchers have focused on EEG patterns and demonstrated that EEG patterns of individuals with epilepsy can be used to predict prognosis and treatment responses. However, accurate EEG analysis requires an experienced epileptologist with several years of training, who are often unavailable in small or medium sized hospitals. In this paper, a novel machine learning (ML) model that accurately distinguishes Benign Epilepsy with Centrotemporal Spikes (BECTS) from Temporal Lobe Epilepsy (TLE) is proposed. BECTS and TLE show different seizure types and age of onset, but differential diagnosis can be challenging due to the similar location and patterns of the EEG spikes. The proposed hybrid machine learning (HML) model processes the diagnosis in the order of (1) creating feature matrices using statistical indexes after signal decomposition, (2) processing feature selection using Support Vector Machine (SVM) technology, and (3) classifying the results through ensemble learning based on decision trees. Simulation was performed using real patient data of 112 BECTS and 112 TLE EEG signals, where training was performed using 80% of the data and 20% of the data was used in the performance analysis comparison with the actual labeled data based on the diagnosis of medical doctors. The performance of the hybrid classification model is compared with other representative ML algorithms, which include logistic regression, KNN, SVM, and ensemble learning based decision tree. The model proposed in this paper shows an accuracy performance exceeding 99%, which is higher than the performance obtainable from the other ML classification models. The purpose of this study is to introduce a novel EEG diagnostic system that shows maximum efficiency to support clinical real-time diagnosis that can accurately distinguish epilepsy types. Future research will focus on expanding this ML model to categorize other types of epilepsies beyond BECTS and TLE and implement the HML diagnostic blockchain database into the hospital system.

Targeting specific pathologic pro-inflammatory cytokines or related molecules leads to excellent therapeutic effects in inflammatory arthritis, including rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. Most of these agents, known as biologic disease-modifying anti-rheumatic drugs (bDMARDs), are produced in live cell lines and are usually monoclonal antibodies. Several types of monoclonal antibodies target different pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-17A, IL-6, and IL-23/12. Some bDMARDs, such as rituximab and abatacept, target specific cell-surface molecules to control the inflammatory response. The therapeutic effects of these bDMARDs differ in different forms of inflammatory arthritis and are associated with different adverse events. In this article, we summarize the therapeutic utility and adverse effects of bDMARDs and suggest future research directions for developing bDMARDs.

Abstract Although extra‐glomerular involvement of microscopic polyangiitis is not regarded as a characteristic finding of the disease, tubulointerstitial nephritis should be considered as a new subclass of renal involvement.

Purpose Childhood absence epilepsy (CAE) is a common form of idiopathic generalized epilepsy with onset middle childhood and has typically a good prognosis, but remission rates vary. We aimed to analyze unfavorable prognostic factors in children initially diagnosed with CAE. Methods We retrospectively reviewed 48 patients under 13 years of age who were diagnosed with CAE at the Severance Children's Hospital, Seoul, Korea. We analyzed clinical information including comorbidity through neuropsychological test. Results Thirteen of the 48 patients (27%) showed an unfavorable prognosis, with clinical seizures or seizure waves on electroencephalogram persistent even after 12 months of anticonvulsant therapy. The mean age at absence seizure onset was 6.51±2.36 years. The most commonly used antiepileptic drug (AED) was ethosuximide, and the median duration of initial AEDs was 25.63±24.41 months. The presence of comorbidity and clinical absence seizures after 6 months of AEDs correlated with an unfavorable prognosis. Motor seizures were the most unfavorable prognostic factor during follow-up. Conclusion This study shows that clinical absence seizures after 6 months of AED, comorbidity, and motor seizure are the most important predictive factors of an unfavorable prognosis for absence epilepsy in childhood. This study suggests that when these factors are observed, early intervention needs to be considered.

Purpose Mutations in the cyclin-dependent kinase-like 5 (CDKL5) gene are associated with epileptic encephalopathy and severe cognitive impairment. We aim to characterize the association between this gene and treatment efficacy. Methods We retrospectively analyzed 10 patients who were treated at Severance Children's Hospital for epileptic encephalopathy who were subsequently diagnosed with a CDKL5 mutation using next-generation sequencing. Results Electroencephalography (EEG) results showed generalized pattern abnormalities in 60% (6/10) of patients with CDKL5 mutations. We analyzed the effects of three treatments, namely antiepileptic drugs (AEDs), ketogenic diet (KD), and steroids. A more than 50% reduction in seizures was observed in 12% (1/8) of patients treated with clobazam. KD treatment proved ineffective in most cases. In addition, a more than 50% reduction in seizures was observed in 57% (4/7) of patients treated with steroids. EEG analysis of patients treated effectively with steroids revealed that 75% (3/4) showed hypsarrhythmia and 25% (1/4) showed focal epileptiform. Conclusion In this study, as in other studies, AEDs and KD did not effectively control seizures in most patients with a CDKL5 mutation. However, steroid therapy reduced the frequency of seizures in patients who also exhibited hypsarrhythmia. This suggests that steroid treatment is helpful in cases of hypsarrhythmia with CDKL5 mutations.

Purpose Acquired epileptic aphasia (AEA) accompanied by electroencephalogram (EEG) abnormality is a rare disease; therefore, there are few studies investigating the prognostic factors and treatment efficacy. We aimed to determine the therapeutic effects and prognostic factors for clinical seizure and neuropsychological function in acquired aphasia patients. Methods We retrospectively studied cases of AEA diagnosed at Severance Children's Hospital from January 2013 to October 2017. We evaluated the efficacy of antiepileptic drugs, steroids, and ketogenic diets (KD) in treating acquired aphasia. The EEG patterns and prognostic factors were predicted by the background EEG and frequency of spike and wave during sleep (SWS). Results The study analyzed 20 patients, 11 male and 9 female, with AEA. Aphasia most commonly occurred at 4 years of age, and clinical seizure was most likely to occur between 2 and 4 years of age and focal seizures were the most common seizure type. KD was shown to be the best treatment for clinical seizure in AEA patients. Patients with normal EEG background showed better responses to clinical seizure treatment and improvements in neuropsychological function. Conclusion KD and steroids generate the best therapeutic effects for clinical seizure in AEA patients. Improvements in neuropsychological function in AEA patients may be related to the EEG background and the SWS patterns. Additionally, the results suggest that the response of clinical seizure to antiepileptic drugs may also be related to the EEG background. However, the current study had some limitations and further research is needed.

Purpose Electroencephalography (EEG) is an effective test in predicting severe cortical dysfunction associated with poor outcomes in adult patients, but its value in pediatric patients remains incomplete. Here, we assessed the prognostic value of EEG regarding sedative history and various etiologies in pediatric patients who had undergone EEGs at the pediatric intensive care unit of Severance Hospital for 5 years. Methods We performed a retrospective study of total 113 pediatric patients who met our criteria. In-hospital mortality was measured for the primary outcome. Results In-hospital mortality was observed in 43 patients (38.1%) and sedatives were used in 37 patients (32.7%). Patients who showed in-hospital mortality were more like to have higher EEG background scores and absent EEG reactivity (P

Genetic diagnosis of patients with neurodevelopmental disorders is imperative and a standard clinical practice. Considering the continuous accumulation of data on disease-causing variants, reanalysis of previously established sequencing data is important. Periodic reanalysis of variants with uncertain significance has become mandatory in clinical laboratories. Therefore, to confirm the utility of the reanalysis of targeted gene panel data in clinical laboratories, we re-evaluated the data of two groups of patients who had undergone targeted gene panel testing for neurodevelopmental disorders (n = 116) and epileptic encephalopathy (n = 384). This reanalysis was based on a reannotation process reflecting updated databases. Six (5.2%) and seven (1.8%) new pathogenic or likely pathogenic variants were identified in these two groups, respectively, attributable to the updated guidelines and de novo reports from unrelated patients. Although relatively low, considerable increase in the diagnostic yield was confirmed. We suggest that reanalysis of genetic variants, mainly using changes in databases and updated interpretations, should be implemented as a routine practice in clinical laboratories.

Abstract Background We intended to evaluate diagnostic utility of a targeted gene sequencing by using next generation sequencing (NGS) panel in patients with intractable early-onset epilepsy (EOE) and find the efficient analytical step for increasing the diagnosis rate. Methods We assessed 74 patients with EOE whose seizures started before 3 years of age using a customized NGS panel that included 172 genes. Single nucleotide variants (SNVs) and exonic and chromosomal copy number variations (CNVs) were intensively examined with our customized pipeline and crosschecked with commercial or pre-built software. Variants were filtered and prioritized by in-depth clinical review, and finally classified according to the American College of Medical Genetics and Genomics guidelines. Each case was further discussed in a monthly consensus meeting that included the participation of all laboratory personnel, bioinformaticians, geneticists, and clinicians. Results The NGS panel identified 28 patients (37.8%) with genetic abnormalities; 25 patients had pathogenic or likely pathogenic SNVs in 17 genes including SXTBP1 (n = 3), CDKL5 (n = 2), KCNQ2 (n = 2), SCN1A (n = 2), SYNGAP1 (n = 2), GNAO1 (n = 2), KCNT1 (n = 2), BRAT1, WWOX, ZEB2, CHD2, PRICKLE2, COL4A1, DNM1, SCN8A, MECP2, SLC9A6 (n = 1). The other 3 patients had pathogenic CNVs (2 duplications and 1 deletion) with varying sizes (from 2.5 Mb to 12 Mb). The overall diagnostic yield was 37.8% after following our step-by-step approach for clinical consensus. Conclusions NGS is a useful diagnostic tool with great utility for patients with EOE. Diagnostic yields can be maximized with a standardized and team-based approach.

Although Bell’s palsy is the most common cause of facial palsy in children, some cases have potentially fatal causes. We report a rare case of isolated facial palsy in a 4-year-old girl whose diagnosis was acute myeloid leukemia with extramedullary infiltration. The findings of laboratory investigations were nonspecific at presentation except that the delta neutrophil index was 34.5% (reference range, 0%-5%). To avoid hasty diagnosis of Bell’s palsy in children with isolated facial palsy, vigilant differential diagnosis and workup are recommended.

To identify genome sequences of Apple scar skin viroid (ASSVd) isolates in Korea, the field survey was performed from ‘Hongro’ apple orchards located in eight sites in South Korea (Bongwha, Cheongsong, Dangjin, Gimchoen, Muju, Mungyeong, Suwon, and Yeongwol). ASSVd was detected by RT-PCR and PCR fragments were cloned into cloning vector. Full-length viral genomes of eight ASSVd isolates were sequenced and compared with 21 isolates reported previously from Korea, India, China, Japan and Greece. Eight isolates in this study showed 92.2-99.7% nucleotide sequence identities with those reported previously. Phylogenetic analysis showed that seven isolates reported in this study belong to the same group distinct from other groups.

BackgroundIt is known that Tuffier's line intersects the spine at the L4 spinous process or at the L4-L5 intervertebral space. Full term parturient women undergo various physical changes. Therefore, determining the vertebral level with Tuffier's line based on palpation inevitably is not very accurate. The aim of this study was to use ultrasound to verify the difference between vertebral levels for the palpated Tuffier's line in parturient and non-parturient women in the lateral decubitus position.MethodsWe consecutively enrolled 40 parturient women at 37-41 weeks of gestation and 40 non-parturient women scheduled for regional anesthesia. In the left lateral position, the location of the vertebra was identified using ultrasonography. We marked every intervertebral space from L5 to L2 vertebra, divided each spinous process into two equal parts, and numbered the spaces sequentially from 1 to 9. We drew a Tuffier's line by palpating, recorded the vertebral level that this line intersected.ResultsThe mean value of an arbitrary number of vertebral level of Tuffier's line was 6.4 ± 0.9 in the non-pregnant group and this represents L4-lower vertebral level. In the pregnant group, the mean value was 3.0 ± 1.0 which represents L3-lower vertebral level. There was a significant difference between the two groups (P < 0.05).ConclusionsWe compared using an available ultrasound technique the vertebral levels intersected by the palpated Tuffier's line between parturient and non-parturient women and found that the vertebral levels were more cephalad in the parturient women compared to the non-parturient women.

In worldwide, viral diseases of apple plants has caused the serious problems like reduced production and malformation of fruits. Also, the damages of apple plants by virus and/or viroid infection (Apple chlorotic leaf spot virus, Apple stem grooving virus, Apple mosaic virus, and Apple scar skin viroid) were reported in Korea. However there is few report about the protection approach against the infection by apple viruses. Therefore, this paper introduced the experimental protocol for the development of virus-free apple cultivars (Danhong, Hongan, Saenara, Summerdream). Apple plants were treated at 37oC for 4 weeks and shoot tips were cultured in vitro. After heat treatment, the detection of apple viruses was performed by RT-PCR using virusspecific detection primers in new apple cultivars. With the heat treatments followed by in vitro shoot tip culture, the proportion of virus-free stocks of ‘Danhong’, ‘Hongan’, ‘Saenara’, and ‘Summerdream’ was 28%, 16%, 12%, and 12%, respectively. Taken together, this approach can be a good tool for production of virus-free apple stocks.

Rubinstein-Taybi syndrome (RTS) is a congenital disorder characterized by typical facial features, broad thumbs and toes, with mental retardation. Additionally, tumors, keloids and various congenital anomalies including congenital heart defects have been reported in RTS patients. In about 50% of the patients, mutations in the CREB binding protein (CREBBP) have been found, which are understood to be associated with cell growth and proliferation. Here, we describe a typical RTS patient with Arnold-Chiari malformation. A mutation in the CREBBP gene, c.4944_4945insC, was identified by mutational analysis.