Echinochrome A (Ech A) isolated from marine organisms is a therapeutic effector for various cardiovascular diseases, but its precise mechanisms are unclear.This study identified the role and mechanisms mediating the effects of Ech A on the migration of vascular smooth muscle cells (VSMCs) induced by high-mobility group box 1 (HMGB1). Compared to the control cells, the migration of VSMCs stimulated with HMGB1 (100 ng/ml) was markedly increased, which was significantly attenuated in cells pretreated with MPIIIB10 (100 ng/ml), a neutralizing monoclonal antibody for osteopontin (OPN). In VSMCs stimulated with HMGB1, the increased expression of OPN mRNA and protein was accompanied by an increased OPN promoter activity. In reporter gene assays using OPN promoter-luciferase constructs, the promoter region 538-234 bp of the transcription start site containing the binding sites for activator protein 1 (AP-1) was shown to be responsible for the increased transcriptional activity by HMGB1. In addition, the binding activity of AP-1 was increased in HMGB1-stimulated cells, highlighting the pivotal role of AP-1 on OPN expression in HMGB1-stimulated VSMCs. An examination of the vascular effects of Ech A showed that the increased AP-1 binding/promoter activities and OPN expression induced by HMGB1 were attenuated in cells pretreated with Ech A (3 or 10 μM). Similarly, Ech A inhibited HMGB1-induced VSMC migration in a concentration-dependent manner. These findings suggest that Ech A inhibits VSMC migration by suppressing OPN expression.Hence, Ech A is suggested as a potential therapeutic strategy for vascular remodeling in the injured vasculatures.

Connective tissue disease (CTD), comprising a range of autoimmune disorders, is often accompanied by lung involvement, which can lead to life-threatening complications. The primary types of CTDs that manifest as interstitial lung disease (ILD) include rheumatoid arthritis, systemic sclerosis, Sjögren’s syndrome, mixed CTD, idiopathic inflammatory myopathies, and systemic lupus erythematosus. CTD-ILD presents a significant challenge in clinical diagnosis and management due to its heterogeneous nature and variable prognosis. Early diagnosis through clinical, serological, and radiographic assessments is crucial for distinguishing CTD-ILD from idiopathic forms and for implementing appropriate therapeutic strategies. Hence, we have reviewed the multiple clinical manifestations and diagnostic approaches for each type of CTD-ILD, acknowledging the diversity and complexity of the disease. The importance of a multidisciplinary approach in optimizing the management of CTD-ILD is emphasized by recent therapeutic advancements, which include immunosuppressive agents, antifibrotic therapies, and newer biological agents targeting specific pathways involved in the pathogenesis. Therapeutic strategies should be customized according to the type of CTD, the extent of lung involvement, and the presence of extrapulmonary manifestations. Additionally, we aimed to provide clinical guidance, including therapeutic recommendations, for the effective management of CTD-ILD, based on patient, intervention, comparison, outcome (PICO) analysis.

Purpose: Adjuvant treatment for craniopharyngioma after surgery is controversial. Adjuvant external beam radiation therapy (EBRT) can increase the risk of long-term sequelae. Stereotactic radiosurgery (SRS) is used to reduce treatment-related toxicity.In this study, we compared the treatment outcomes and toxicities of adjuvant therapies for craniopharyngioma. Materials and Methods: We analyzed patients who underwent craniopharyngioma tumor removal between 2000 and 2017. Of the 153 patients, 27 and 20 received adjuvant fractionated EBRT and SRS, respectively. We compared the local control (LC), progression-free survival (PFS), and overall survival between groups that received adjuvant fractionated EBRT, SRS, and surveillance. Results: The median follow-up period was 77.7 months. For SRS and surveillance, the 10-year LC was 57.2% and 57.4%, respectively. No local progression was observed after adjuvant fractionated EBRT. One patient in the adjuvant fractionated EBRT group died owing to glioma 94 months after receiving radiotherapy (10-year PFS: 80%). The 10-year PFS was 43.6% and 50.7% in the SRS and surveillance groups, respectively. The treatment outcomes significantly differed according to adjuvant treatment in nongross total resection (GTR) patients. Additional treatment-related toxicity was comparable in the adjuvant fractionated EBRT and other groups. Conclusion Adjuvant fractionated EBRT could be effective in controlling local failure, especially in patients with non-GTR, while maintaining acceptable treatment-related toxicity.

Purpose: Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS. Materials and Methods: This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches. Results: TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making. Conclusion TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

Purpose: Hematopoietic stem cell transplantation (HSCT) has been an important method of treatment in the advance of pediatric acute lymphoblastic leukemia (ALL). The indications for HSCT are evolving and require updated establishment. In this study, we aimed to investigate the efficacy of HSCT on the treatment outcome of pediatric ALL, considering the indications for HSCT and subgroups. Materials and Methods: A retrospective analysis was conducted on ALL patients diagnosed and treated at a single center. Risk groups were categorized based on age at diagnosis, initial white blood cell count, disease lineage (B/T), and cytogenetic study results. Data on the patients’ disease status at HSCT and indications of HSCT were collected. Indications for HSCT were categorized as upfront HSCT at 1st complete remission, relapse, and refractory disease. Results: Among the 549 screened patients, a total of 418 patients were included in the study; B-cell ALL (n=379) and T-cell ALL (T-ALL) (n=39). HSCT was conducted on a total of 106 patients (25.4%), with a higher frequency as upfront HSCT in higher-risk groups and specific cytogenetics. The overall survival (OS) was significantly better when done upfront than in relapsed or refractory state in T-ALL patients (p=0.002). The KMT2A-rearranged ALL patients showed superior event-free survival (p=0.002) and OS (p=0.022) when HSCT was done as upfront treatment. Conclusion HSCT had a substantial positive effect in a specific subset of pediatric ALL. In particular, frontline HSCT for T-ALL and KMT2A-rearranged ALL offered a better prognosis than when HSCT was conducted in a relapsed or refractory setting.

Background: Sarcopenia, a multifactorial disorder involving metabolic disturbance, suggests potential for metabolite biomarkers. Carnitine (CN), essential for skeletal muscle energy metabolism, may be a candidate biomarker. We investigated whether CN metabolites are biomarkers for sarcopenia. Methods: Associations between the CN metabolites identified from an animal model of sarcopenia and muscle cells and sarcopenia status were evaluated in men from an age-matched discovery (72 cases, 72 controls) and a validation (21 cases, 47 controls) cohort. Results: An association between CN metabolites and sarcopenia showed in mouse and cell studies. In the discovery cohort, plasma C5-CN levels were lower in sarcopenic men (P=0.005). C5-CN levels in men tended to be associated with handgrip strength (HGS) (P=0.098) and were significantly associated with skeletal muscle mass (P=0.003). Each standard deviation increase in C5-CN levels reduced the odds of low muscle mass (odd ratio, 0.61; 95% confidence interval [CI], 0.42 to 0.89). The area under the receiver operating characteristic curve (AUROC) of CN score using a regression equation of C5-CN levels, for sarcopenia was 0.635 (95% CI, 0.544 to 0.726). In the discovery cohort, addition of CN score to HGS significantly improved AUROC from 0.646 (95% CI, 0.575 to 0.717; HGS only) to 0.727 (95% CI, 0.643 to 0.810; P=0.006; HGS+CN score). The improvement was confirmed in the validation cohort (AUROC=0.563; 95% CI, 0.470 to 0.656 for HGS; and AUROC=0.712; 95% CI, 0.569 to 0.855 for HGS+CN score; P=0.027). Conclusion C5-CN, indicative of low muscle mass, is a potential circulating biomarker for sarcopenia in men. Further studies are required to confirm these results and explore sarcopenia-related metabolomic changes.

Background/Aims: We investigated the clinical practice patterns of Korean endoscopists for the endoscopic resection of colorectal polyps. Methods: From September to November 2021, an online survey was conducted regarding the preferred resection methods for colorectal polyps, and responses were compared with the international guidelines. Results: Among 246 respondents, those with <4 years, 4–9 years, and ≥10 years of experiencein colonoscopy practices accounted for 25.6%, 34.1%, and 40.2% of endoscopists, respectively. The most preferred resection methods for non-pedunculated lesions were cold forceps polypectomy for ≤3 mm lesions (81.7%), cold snare polypectomy for 4–5 mm (61.0%) and 6–9 mm (43.5%) lesions, hot endoscopic mucosal resection (EMR) for 10–19 mm lesions (72.0%), precut EMR for 20–25 mm lesions (22.0%), and endoscopic submucosal dissection (ESD) for ≥26 mm lesions (29.3%). Hot EMR was favored for pedunculated lesions with a head size <20 mm and stalk size <10 mm (75.6%) and for those with a head size ≥20 mm or stalk size ≥10 mm (58.5%). For suspected superficial and deep submucosal lesions measuring 10–19 mm and ≥20 mm, ESD (26.0% and 38.6%) and surgery (36.6% and 46.3%) were preferred, respectively. The adherence rate to the guidelines ranged from 11.2% to 96.9%, depending on the size, shape, and histology of the lesions. Conclusions Adherence to the guidelines for endoscopic resection techniques varied depend-ing on the characteristics of colorectal polyps. Thus, an individualized approach is required to increase adherence to the guidelines.

Background/Aims: The Korean guidelines for Helicobacter pylori treatment were revised in 2020, however, the extent of adherence to these guidelines in clinical practice remains unclear. Herein, we initiated a prospective, nationwide, multicenter registry study in 2021 to evaluate the current management of H.pylori infection in Korea. Methods: This interim report describes the adherence to the revised guidelines and their impact on firstline eradication rates. Data on patient demographics, diagnoses, treatments, and eradication outcomes were collected using a web-based electronic case report form. Results: A total of 7,261 patients from 66 hospitals who received first-line treatment were analyzed.The modified intention-to-treat eradication rate for first-line treatment was 81.0%, with 80.4% of the prescriptions adhering to the revised guidelines. The most commonly prescribed regimen was the 14-day clarithromycin-based triple therapy (CTT; 42.0%), followed by tailored therapy (TT; 21.2%), 7-day CTT (14.1%), and 10-day concomitant therapy (CT; 10.1%). Time-trend analysis demonstrated significant increases in guideline adherence and the use of 10-day CT and TT, along with a decrease in the use of 7-day CTT (all p<0.001). Multivariate logistic regression analysis revealed that guideline adherence was significantly associated with first-line eradication success (odds ratio, 2.03; 95% confidence interval, 1.61 to 2.56; p<0.001). Conclusions The revised guidelines for the treatment of H. pylori infection have been increasingly adopted in routine clinical practice in Korea, which may have contributed to improved first-line eradication rates. Notably, the 14-day CTT, 10-day CT, and TT regimens are emerging as the preferred first-line treatment options among Korean physicians.

Purpose: This study investigated urinary incontinence (UI) following holmium laser enucleation of the prostate (HoLEP), based on the postoperative period, type of UI, and severity according to prostate volume. Methods: We analyzed prospectively collected data from patients who underwent HoLEP for benign prostatic hyperplasia at Seoul National University Hospital between January 2010 and June 2022. Patients were followed-up at 2 weeks, 3 months, and 6 months postoperatively. The patients were divided into 3 prostate volume groups: A (30–80 mL), B (81–120 mL), and C (>120 mL). We compared clinical outcomes and UI rates between the groups. Results: In total, 1,675 patients were included. The preoperative urgency UI (UUI) rate was 16.1%, with no significant difference between the groups (P=0.81). Two weeks postoperatively, the UUI rate was 6.0% (including a de novo UUI rate of 4.2%), with no significant differences between the groups. The stress UI (SUI) rate at 2 weeks postoperatively was 6.3%, and increased with larger prostate volume (P=0.04). The UUI and SUI rates decreased to 0.9% and 1.2%, respectively, 6 months postoperatively. Six months postoperatively, the SUI rate was significantly lower in group A (P=0.02), whereas the UUI rate did not differ between the groups (P=0.69). Conclusions Our results demonstrated that the preoperative UUI rate was high at baseline. Both the UUI and SUI rates continuously decreased up to 6 months postoperatively. Although the SUI rates significantly differed according to prostate volume, there was no significant difference in the UUI rate.

Background: and Purpose Treatments for neuromyelitis optica spectrum disorder (NMOSD) such as eculizumab, ravulizumab, satralizumab, and inebilizumab have significantly advanced relapse prevention, but they remain expensive. Rituximab is an off-label yet popular alternative that offers a cost-effective solution, but its real-world efficacy needs better quantification for guiding the application of newer approved NMOSD treatments (ANTs). This study aimed to determine real-world rituximab failure rates to anticipate the demand for ANTs and aid in resource allocation. Methods: We conducted a nationwide retrospective study involving 605 aquaporin-4-antibody-positive NMOSD patients from 22 centers in South Korea that assessed the efficacy and safety of rituximab over a median follow-up of 47 months. Results: The 605 patients treated with rituximab included 525 (87%) who received continuous therapy throughout the follow-up period (median=47 months, interquartile range=15–87 months). During this period, 117 patients (19%) experienced at least 1 relapse. Notably, 68 of these patients (11% of the total cohort) experienced multiple relapses or at least 1 severe relapse.Additionally, 2% of the patients discontinued rituximab due to adverse events, which included severe infusion reactions, neutropenia, and infections. Conclusions This study has confirmed the efficacy of rituximab in treating NMOSD, as evidenced by an 87% continuation rate among patients over a 4-year follow-up period. Nevertheless, the occurrence of at least one relapse in 19% of the cohort, including 11% who experienced multiple or severe relapses, and a 2% discontinuation rate due to adverse events highlight the urgent need for alternative therapeutic options.