Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that culminates in respiratory failure and death due to irreversible scarring of the distal lung. While initially considered a chronic inflammatory disorder, the aberrant function of the alveolar epithelium is now acknowledged as playing a central role in the pathophysiology of IPF. This study aimed to investigate the regenerative capacity of alveolar type 2 (AT2) cells using IPF-derived alveolar organoids and to examine the effects of disease progression on this capacity. Methods: Lung tissues from three pneumothorax patients and six IPF patients (early and advanced stages) were obtained through video-assisted thoracoscopic surgery and lung transplantation. HTII-280+ cells were isolated from CD31-CD45-epithelial cell adhesion molecule (EpCAM)+ cells in the distal lungs of IPF and pneumothorax patients using fluorescence-activated cell sorting (FACS) and resuspended in 48-well plates to establish IPF-derived alveolar organoids. Immunostaining was used to verify the presence of AT2 cells. Results: FACS sorting yielded approximately 1% of AT2 cells in early IPF tissue, and the number decreased as the disease progressed, in contrast to 2.7% in pneumothorax. Additionally, the cultured organoids in the IPF groups were smaller and less numerous compared to those from pneumothorax patients. The colony forming efficiency decreased as the disease advanced. Immunostaining results showed that the IPF organoids expressed less surfactant protein C (SFTPC) compared to the pneumothorax group and contained keratin 5+ (KRT5+) cells. Conclusion This study confirmed that the regenerative capacity of AT2 cells in IPF decreases as the disease progresses, with IPF-derived AT2 cells inherently exhibiting functional abnormalities and altered differentiation plasticity.

Background: s/Aims: Hepatocellular carcinoma (HCC) is a malignant cancer with an increasing incidence worldwide. Although numerous efforts have been made to identify effective therapies for HCC, current strategies have limitations. We present a new approach for targeting L-arginine and argininosuccinate synthetase 1 (ASS1). Methods: ASS1 expression in HCC cell lines and primary hepatocytes was detected using polymerase chain reaction and western blotting. Proliferation, migration, signaling pathways, and nitric oxide production in HCC cell lines were measured using MTS, colony formation, wound healing, Western blot, and Griess assays. Results: ASS1 expression varied among the HCC cell lines, and cisplatin cytotoxicity was ASS1-dependent. L-arginine alone induced apoptosis in HCC cell lines, regardless of ASS1 expression; however, its effect was enhanced in ASS1-expressing HCC cell lines. Cisplatin cytotoxicity also increased, suggesting that L-arginine acts as a sensitizer to cisplatin in HCC cell lines. ASS1 and L-arginine produced nitric oxide and inhibited key proliferation- and survival-related signaling pathways such as PI3K/Akt and MAPK. Additionally, ASS1 and L-arginine reduced the expression of PKM1 and PKM2 in the glycolysis pathway. Conclusions Our study revealed that ASS1 and L-arginine exhibited anticancer effects in HCC and sensitized cisplatin-resistant HCC cells to chemotherapy. The combination of ASS1 and L-arginine significantly enhanced the anticancer effects, even in HCC cell lines with low or absent ASS1 expression. These findings highlight the critical roles of arginine and ASS1 in HCC and suggest that increasing arginine availability could be a promising therapeutic strategy.

Background: To identify the optimal surgical technique for single-level anterior cervical discectomy and fusion (ACDF), this study compared surgical outcomes and incidence of adjacent segment degeneration (ASD) in patients undergoing single-level ACDF using cage alone single-level fusion and plate fixation techniques. Methods: This single-center retrospective study (2003–2018) included patients who underwent single-level ACDF with either plate fixation (PLATE) or cage (CAGE) alone. The radiologic and clinical outcomes between the 2 surgical groups were compared over a 4-year follow-up period. Outcomes of interest included parameters related to range of motion, sagittal alignment, as well as fusion, subsidence, and ASD rates. Clinical outcomes were evaluated using the Neck Disability Index (NDI) and visual analog scale (VAS) for pain. Dysphagia and hoarseness rates were estimated based on medical records. Results: Forty-seven patients were included (n=17 in CAGE group). In the CAGE group, 94.1% of the patients had Bridwell grade 1 or 2, compared to 83.3% in the PLATE group (p = 0.396). Subsidence occurred in 12.5% and 3.6% of the CAGE and PLATE cases, respectively (p = 0.543). Segmental kyphosis progressed in the CAGE group compared to the PLATE group at 12, 24, and 48 months (p < 0.001). Radiographic ASD was observed in 41.2% and 30.0% of patients in the CAGE and PLATE groups, respectively, with a higher incidence in the upper segments for both groups. Preoperative NDI scores were similar between the groups; however, postoperatively, the CAGE group had significantly lower NDI scores (3.50 ± 2.74 vs. 8.00 ± 5.81) at 4 years (p = 0.020). Neck pain VAS scores also showed significant improvement in the CAGE group (2.33 ± 2.94) compared with that in the PLATE group (3.07 ± 2.31) at 4 years (p = 0.045). Both groups showed comparable arm pain VAS scores at 2 and 4 years postoperatively. Postoperative dysphagia occurred in 1 patient in the PLATE group, resolving almost completely by 1 year. Conclusions Single-level ACDF using a cage alone technique demonstrated favorable radiologic and clinical outcomes overall compared to plate-augmented ACDF. However, plate augmentation is recommended for patients with severe cervical kyphosis or those at high risk of subsidence.

Background: and Purpose: This clinical practice guideline provides evidence-based recommendations for treatment of dementia, focusing on cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists for Alzheimer’s disease (AD) and other types of dementia. Methods: Using the Population, Intervention, Comparison, Outcomes (PICO) framework, we developed key clinical questions and conducted systematic literature reviews. A multidisciplinary panel of experts, organized by the Korean Dementia Association, evaluated randomized controlled trials and observational studies. Recommendations were graded for evidence quality and strength using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Results: Three main recommendations are presented: (1) For AD, cholinesterase inhibitors (donepezil, rivastigmine, galantamine) are strongly recommended for improving cognition and daily function based on moderate evidence; (2) Cholinesterase inhibitors are conditionally recommended for vascular dementia and Parkinson’s disease dementia, with a strong recommendation for Lewy body dementia; (3) For moderate to severe AD, NMDA receptor antagonist (memantine) is strongly recommended, demonstrating significant cognitive and functional improvements. Both drug classes showed favorable safety profiles with manageable side effects. Conclusions This guideline offers standardized, evidence-based pharmacologic recommendations for dementia management, with specific guidance on cholinesterase inhibitors and NMDA receptor antagonists. It aims to support clinical decision-making and improve patient outcomes in dementia care. Further updates will address emerging treatments, including amyloid-targeting therapies, to reflect advances in dementia management.

Background: Insulin resistance (IR) is central to metabolic disorders and significantly influenced by diet. Studies on meal frequency (MF) and metabolic indicators have shown mixed results. This study explores the link between MF and IR in middle-aged and older adults. Methods: This prospective cohort study included 4,570 adults aged 40 to 69 years from the Korean Genome and Epidemiologic Study. MF were divided into two groups based on whether they consumed three or more, or fewer than three, meals daily. IR was evaluated using the homeostasis model assessment of insulin resistance (HOMA-IR); participants were classified as IR if their HOMA-IR value was ≥2.5. Multiple Cox proportional hazard regression analyses were conducted to examine the association between MF and the incidence of IR. Results: After adjusting for all variables, individuals in the MF ≥3 group showed a reduced incidence of IR compared to those in the MF <3 group (hazard ratio, 0.880; 95% confidence interval, 0.782 to 0.990). Additionally, subgroup analyses by sex, diabetes mellitus (DM), and body mass index (BMI) showed that this association persisted only in men, individuals without DM, and those with a BMI <25. Conclusion Our findings indicate that a higher MF among middle-aged and older adults is associated with a reduced incidence of IR. However, this association was maintained only in men, individuals without DM, and those without obesity.

Background/Aims: Magnifying endoscopy with narrow-band imaging (ME-NBI) enables the visualization of detailed microsurface (MS) and microvascular (MV) structures in the gastrointestinal tract. White globe appearance (WGA) is a small whitish lesion with a globular shape identified during ME-NBI for early gastric cancer (EGC). This study aimed to investigate the associations between WGA, clinicopathological characteristics, and other ME-NBI findings in patients with EGC. Methods: The presence or absence of WGA in 122 patients (126 lesions) with an endoscopic diagnosis of EGC who underwent ME-NBI before endoscopic or surgical resection was prospectively collected and retrospectively analyzed. During ME-NBI, the MS and MV patterns and the presence of WGA and white opaque substances (WOS) were investigated. EGC cases were categorized as differentiated or undifferentiated type, and mucosal, submucosal, or advanced. Results: Of 126 lesions, WGA was observed in 25 (19.8%). WGA was associated with tumor size (≤2 cm [17/63, 27.0%] vs >2 cm [8/63, 12.7%]; p=0.044), histologic type differentiated type [22/89, 24.7%] vs undifferentiated type [3/37. 8.1%]; p=0.033), and tumor location (upper third [1/11, 9.1%] vs middle third [18/58, 31.0%] and lower third [6/57, 10.5%]; p=0.017). Although WGA was observed more frequently in lesions with an oval/tubular MS pattern, a fine-network MV pattern, and the absence of WOS, the difference was not statistically significant (MS pattern, p=0.358; MV pattern, p=0.212; WOS, p=0.121, respectively). Conclusions WGA was associated with small tumor size, differentiated-type histology, and middle-third tumor location, and was more frequently observed in lesions with an oval/tubular MS and fine-network MV patterns and the absence of WOS.

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.

Background: Osteoporosis is a significant public health issue in aging populations. Despite advances in pharmacotherapy, underdiagnosis and undertreatment remain prevalent even in patients with recent fractures. This study examined 20-year trends (2002– 2022) in anti-osteoporotic medication (AOM) usage in South Korea. Methods: Data from the Korean National Health Information Database were retrospectively analyzed. The study included individuals aged ≥50 years and analyzed prescription trends, medication adherence, measured by the medication possession ratio (MPR), and treatment initiation rates post-fracture. The AOMs examined included bisphosphonates, selective estrogen receptor modulators, denosumab (DMAB), teriparatide (TPTD), and romosozumab (ROMO). Results: Over two decades, AOM use has shifted significantly from oral to injectable formulations, with injectables surpassing oral medications in 2020; from 397,440 prescriptions in 2016 to 1,162,779 in 2022. Prescriptions for DMAB surged following its approval as a first-line therapy in 2019, increasing 2.65 times from 217,606 in 2019 to 575,595 in 2022. The MPR improved from 35.4% in 2003 to 73.2% in 2021, with females demonstrating higher adherence than males. Post-fracture treatment rates increased from 31.1% in 2006 to 39.9% in 2021 but remained below 50%. Vertebral fractures had the highest treatment initiation rates, while anabolic agents, such as TPTD and ROMO were underprescribed despite their efficacy. Conclusions This 20-year analysis highlights significant progress in osteoporosis management in South Korea, including a shift towards injectable therapies and improved adherence. However, the persistent undertreatment of high-risk patients underscores the requirement for enhanced access to anabolic agents, clinician education, and policy reforms to optimize post-fracture care.

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.

Background: Because of the low prevalence of inherited retinal diseases, reports on the distribution of retinitis pigmentosa (RP)-related genes in Korean patients are scarce. The aim of this study was to determine the mutation spectrum and allele frequency and observe the final diagnoses in a Korean cohort clinically diagnosed with RP. Methods: We used whole-exome sequencing (WES) to analyze a Korean cohort of 100 unrelated patients clinically diagnosed with RP. The possible pathogenicity of each variant was assessed based on the guidelines of the American College of Medical Genetics and Genomics and Association for Molecular Pathology, in-silico prediction tools, known clinical phenotypes, and inheritance patterns. Results: Definite causative genes were detected in 60/100 patients (60.0%). Of these 60 cases, USH2A was the most common causative gene (14/60, 23.3%), followed by EYS (13/60, 21.7%) and RP1 (6/60, 10.0%). The clinical diagnosis was redefined in 9 of the 60 probands (15.0%) with causative genes after WES. Five of the 60 patients (8.3%) carried a causative variant in CHM, and the clinical diagnosis was redefined as choroideremia. Leber congenital amaurosis was diagnosed in 2/60 probands (3.3%), and RDH12 and RPGRIP1 were the causative genes in each patient. One patient (1/60, 1.7%) was diagnosed with Bietti’s crystalline dystrophy, with CYP4V2 identified as the causative gene. In another patient (1/60, 1.7%), ABCA4 variants were detected with clinical findings suggestive of cone-rod dystrophy. Conclusion This study reports the mutational spectrum of a cohort of Korean patients with a clinical diagnosis of RP who were referred for genetic testing. This study adds valuable data regarding the frequency of genes as well as their relation to the age of symptom onset and relation to other inherited retinal degenerations.