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.

Purpose: Recent development in perioperative treatment of resectable non–small cell lung cancer (NSCLC) have changed the landscape of early lung cancer management. The ADAURA trial has demonstrated the efficacy of adjuvant osimertinib treatment in resectable NSCLC patients; however, studies are required to show which subgroup of patients are at a high risk of relapse and require adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor treatment. This study evaluated risk factors for postoperative relapse among patients who underwent complete resection. Materials and Methods: Data were obtained from the Korean Association for Lung Cancer Registry (KALC-R), a database created using a retrospective sampling survey by the Korean Central Cancer Registry (KCCR) and the Lung Cancer Registration Committee. Results: A total of 3,176 patients who underwent curative resection was evaluated. The mean observation time was approximately 35.4 months. Among stage I to IIIA NSCLC patients, the EGFR-mutant subgroup included 867 patients, and 75.2%, 11.2%, and 11.8% were classified as stage I, stage II, and stage III, respectively. Within the EGFR-mutant subgroup, 44 (5.1%) and 121 (14.0%) patients showed early and late recurrence, respectively. Multivariate analysis on association with postoperative relapse among the EGFR-mutant subgroup showed that age, pathologic N and TNM stages, pleural invasion status, and surgery type were independent significant factors. Conclusion Among the population that underwent complete resection for early NSCLC with EGFR mutation, patients with advanced stage, pleural invasion, or limited resection are more likely to show postoperative relapse.

Purpose: Some studies suggest that TP53 mutations are associated with the response to immune checkpoint inhibitors (ICI) in patients with non–small cell lung cancer (NSCLC) and also contribute to sex disparities in several cancers. Thus, we hypothesized that TP53 mutations might serve as sex-dependent genomic biomarkers of ICI treatment response in patients with NSCLC. Materials and Methods: Clinical data of 100 patients with metastatic NSCLC treated with ICI monotherapy at Seoul National University Bundang Hospital (SNUBH) were retrospectively reviewed. Genomic and clinical datasets of The Cancer Genome Atlas and an ICI-treated lung cancer cohort (cBioPortal) were also analyzed. Results: In SNUBH cohort, no statistically significant difference was observed in the median progression-free survival (PFS) according to TP53 mutation status (p=0.930); however, female patients with TP53 mutations (MT) had a significantly prolonged median PFS compared to wild-type (WT) (6.1 months in TP53 MT vs. 2.6 months in TP53 WT; p=0.021). Programmed death-ligand 1 (PD-L1) high (≥ 50%) expression was significantly enriched in female patients with TP53 MT (p=0.005). The analysis from publicly available dataset also revealed that females with NSCLC with TP53 MT showed significantly longer PFS than those with TP53 WT (p < 0.001). In The Cancer Genome Atlas analysis, expression of immune-related genes, and tumor mutation burden score in TP53 MT females were higher than in males without TP53 MT. Conclusion Female patients with NSCLC with TP53 mutations had high PD-L1 expression and showed favorable clinical outcomes following ICI therapy, suggesting a need for further research to explore the role of TP53 mutations for sex disparities in response to ICI therapy.

Background/Aims: Findings on the impact of Helicobacter pylori eradication on metabolic parameters are inconsistent. This study aimed to evaluate the effects of H. pylori eradication on metabolic parameters and body composition, including body fat mass and skeletal muscle mass. Methods: We retrospectively reviewed the data of asymptomatic patients who underwent health screenings, including bioelectrical impedance analysis, before and after H. pylori eradication between 2005 and 2021. After matching individuals based on key factors, we compared lipid profiles, metabolic parameters, and body composition between 823 patients from the eradicated group and 823 patients from the non-eradicated groups. Results: Blood pressure, erythrocyte sedimentation rate, and glycated hemoglobin values were significantly lower in the eradicated group than in the non-eradicated group. However, changes in body mass index (BMI), body fat mass, appendicular skeletal muscle mass (ASM), waist circumference, and lipid profiles were not significantly different between the two groups. In a subgroup analysis of individuals aged >45 years, blood pressure, erythrocyte sedimentation rate, and glycated hemoglobin changes were significantly lower in the eradicated group than in the noneradicated group. BMI values were significantly higher in the eradicated group than in the noneradicated group; however, no significant differences were observed between the two groups regarding changes in body weight, body fat mass, ASM, or waist circumference. Total cholesterol and low-density lipoprotein cholesterol levels were significantly lower in the eradicated group than in non-eradicated group. Conclusions H. pylori eradication significantly reduced blood pressure, glucose levels, and systemic inflammation and improved lipid profiles in patients aged >45 years. BMI, body fat mass, ASM, and waist circumference did not significantly differ between patients in the eradicated group and those in the non-eradicated group.

Background: and Purpose This study evaluated the diagnostic utility of an anti-signal-recognition particle 54 (anti-SRP54) antibody-based enzyme-linked immunosorbent assay (ELISA) as well as the clinical, serological, and pathological characteristics of patients with SRP immune-mediated necrotizing myopathy (IMNM). Methods: We evaluated 87 patients with idiopathic inflammatory myopathy and 107 healthy participants between January 2002 and December 2023. The sensitivity and specificity of the ELISA for anti-SRP54 antibodies were assessed, and the clinical profiles of patients with antiSRP54 antibodies were determined. Results: The ELISA for anti-SRP54 antibodies had a sensitivity and specificity of 88% and 99%, respectively, along with a test–retest reliability of 0.92 (p<0.001). The 32 patients diagnosed with anti-SRP IMNM using a line-blot immunoassay included 28 (88%) who tested positive for anti-SRP54 antibodies using the ELISA, comprising 12 (43%) males and 16 (57%) females whose median ages at symptom onset and diagnosis were 43.0 years and 43.5 years, respectively. Symptoms included proximal muscle weakness in all 28 (100%) patients, neck weakness in 9 (32%), myalgia in 15 (54%), dysphagia in 5 (18%), dyspnea in 4 (14%), dysarthria in 2 (7%), interstitial lung disease in 2 (7%), and myocarditis in 2 (7%). The median serum creatine kinase (CK) level was 7,261 U/L (interquartile range: 5,086–10,007 U/L), and the median anti-SRP54 antibody level was 2.0 U/mL (interquartile range: 1.0–5.6 U/mL). The serum CK level was significantly higher in patients with coexisting anti-Ro-52 antibodies. Conclusions This study has confirmed the reliability of the ELISA for anti-SRP54 antibodies and provided insights into the clinical, serological, and pathological characteristics of South Korean patients with anti-SRP IMNM.

Background: and Purpose The National Brain Biobank of Korea (NBBK) is a brain bank consortium supported by the Korea Disease Control and Prevention Agency and the Korea National Institute of Health, and was launched in 2015 to support research into neurodegenerative disease dementia (NDD). This study aimed to introduce the NBBK and describes clinicopathological correlations based on analyses of data collected from the NBBK. Methods: Four hospital-based brain banks have been established in South Korea: Samsung Medical Center Brain Bank (SMCBB), Seoul National University Hospital Brain Bank (SNUHBB), Pusan National University Hospital Brain Bank (PNUHBB), and Myongji Hospital Brain Bank (MJHBB). Clinical and pathological data were collected from these brain banks using standardized protocols. The prevalence rates of clinical and pathological diagnoses were analyzed in order to characterize the clinicopathological correlations. Results: Between August 2016 and December 2023, 185 brain specimens were collected and pathologically evaluated (SNUHBB: 117; PNUHBB: 27; SMCBB: 34; MJHBB: 7). The age at consent was 70.8±12.6 years, and the age at autopsy was 71.7±12.4 years. The four-most-common clinical diagnoses were Alzheimer’s disease (AD) dementia (20.0%), idiopathic Parkinson’s disease (15.1%), unspecified dementia (11.9%), and cognitively unimpaired (CU) (11.4%).Most cases of unspecified dementia had a pathological diagnosis of central nervous system (CNS) vasculopathy (31.8%) or AD (31.8%). Remarkably, only 14.2% of CU cases had normal pathological findings. The three-most-common pathological diagnoses were AD (26.5%), CNS vasculopathy (14.1%), and Lewy body disease (13.5%). Conclusions These clinical and neuropathological findings provide a deeper understanding of the mechanisms underlying NDD in South Korea.

Background: The Korean National Cancer Screening Program (NCSP) for gastric cancer requires economic evaluation due to the low sensitivity of upper gastrointestinal series (UGIs) and the associated low cancer survival rate. This study aimed to ascertain the most cost-effective strategy for the NCSP. Methods: The hypothetical target population of this study was aged 40 years or older, and no actual participants were involved. Markov simulation models were constructed for 25 strategies, combinations of 1) screening methods (UGIs or endoscopy vs. endoscopy-only), 2) screening intervals (one, two, or three-year), and 3) upper age limit of screening (69, 74, 79 years old, or “no limit”). Costs, utility, and other input parameters were extracted from various databases and previous studies. Cost-utility, sensitivity, and scenario analyses were conducted. Results: The endoscopy-only strategy with a three-year interval with an upper age limit of 69 was the most cost-effective strategy with an incremental cost-utility ratio of KRW 13,354,106 per quality-adjusted life years. According to the probabilistic sensitivity analysis, the uncertainty of the result was significantly small. Scenario analysis is showed that as the screening rate increased, the endoscopy-only strategy saved more costs compared to the current NCSP. Therefore, it is important to maintain a high screening rate when altering the NCSP strategy. Conclusion Endoscopy-only screening was more cost-effective method than UGIs for the NCSP. Furthermore, a three-year interval with an upper-age limit of 69 years was the most cost-effective strategy. Efforts to improve cost-effective screening guidelines will support the efficient use of medical resources. Additionally, maintaining a higher screening rate may maximize the impact of the modification in strategy on cost-effectiveness.

Purpose: Recent development in perioperative treatment of resectable non–small cell lung cancer (NSCLC) have changed the landscape of early lung cancer management. The ADAURA trial has demonstrated the efficacy of adjuvant osimertinib treatment in resectable NSCLC patients; however, studies are required to show which subgroup of patients are at a high risk of relapse and require adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor treatment. This study evaluated risk factors for postoperative relapse among patients who underwent complete resection. Materials and Methods: Data were obtained from the Korean Association for Lung Cancer Registry (KALC-R), a database created using a retrospective sampling survey by the Korean Central Cancer Registry (KCCR) and the Lung Cancer Registration Committee. Results: A total of 3,176 patients who underwent curative resection was evaluated. The mean observation time was approximately 35.4 months. Among stage I to IIIA NSCLC patients, the EGFR-mutant subgroup included 867 patients, and 75.2%, 11.2%, and 11.8% were classified as stage I, stage II, and stage III, respectively. Within the EGFR-mutant subgroup, 44 (5.1%) and 121 (14.0%) patients showed early and late recurrence, respectively. Multivariate analysis on association with postoperative relapse among the EGFR-mutant subgroup showed that age, pathologic N and TNM stages, pleural invasion status, and surgery type were independent significant factors. Conclusion Among the population that underwent complete resection for early NSCLC with EGFR mutation, patients with advanced stage, pleural invasion, or limited resection are more likely to show postoperative relapse.

Purpose: Some studies suggest that TP53 mutations are associated with the response to immune checkpoint inhibitors (ICI) in patients with non–small cell lung cancer (NSCLC) and also contribute to sex disparities in several cancers. Thus, we hypothesized that TP53 mutations might serve as sex-dependent genomic biomarkers of ICI treatment response in patients with NSCLC. Materials and Methods: Clinical data of 100 patients with metastatic NSCLC treated with ICI monotherapy at Seoul National University Bundang Hospital (SNUBH) were retrospectively reviewed. Genomic and clinical datasets of The Cancer Genome Atlas and an ICI-treated lung cancer cohort (cBioPortal) were also analyzed. Results: In SNUBH cohort, no statistically significant difference was observed in the median progression-free survival (PFS) according to TP53 mutation status (p=0.930); however, female patients with TP53 mutations (MT) had a significantly prolonged median PFS compared to wild-type (WT) (6.1 months in TP53 MT vs. 2.6 months in TP53 WT; p=0.021). Programmed death-ligand 1 (PD-L1) high (≥ 50%) expression was significantly enriched in female patients with TP53 MT (p=0.005). The analysis from publicly available dataset also revealed that females with NSCLC with TP53 MT showed significantly longer PFS than those with TP53 WT (p < 0.001). In The Cancer Genome Atlas analysis, expression of immune-related genes, and tumor mutation burden score in TP53 MT females were higher than in males without TP53 MT. Conclusion Female patients with NSCLC with TP53 mutations had high PD-L1 expression and showed favorable clinical outcomes following ICI therapy, suggesting a need for further research to explore the role of TP53 mutations for sex disparities in response to ICI therapy.

Background/Aims: Findings on the impact of Helicobacter pylori eradication on metabolic parameters are inconsistent. This study aimed to evaluate the effects of H. pylori eradication on metabolic parameters and body composition, including body fat mass and skeletal muscle mass. Methods: We retrospectively reviewed the data of asymptomatic patients who underwent health screenings, including bioelectrical impedance analysis, before and after H. pylori eradication between 2005 and 2021. After matching individuals based on key factors, we compared lipid profiles, metabolic parameters, and body composition between 823 patients from the eradicated group and 823 patients from the non-eradicated groups. Results: Blood pressure, erythrocyte sedimentation rate, and glycated hemoglobin values were significantly lower in the eradicated group than in the non-eradicated group. However, changes in body mass index (BMI), body fat mass, appendicular skeletal muscle mass (ASM), waist circumference, and lipid profiles were not significantly different between the two groups. In a subgroup analysis of individuals aged >45 years, blood pressure, erythrocyte sedimentation rate, and glycated hemoglobin changes were significantly lower in the eradicated group than in the noneradicated group. BMI values were significantly higher in the eradicated group than in the noneradicated group; however, no significant differences were observed between the two groups regarding changes in body weight, body fat mass, ASM, or waist circumference. Total cholesterol and low-density lipoprotein cholesterol levels were significantly lower in the eradicated group than in non-eradicated group. Conclusions H. pylori eradication significantly reduced blood pressure, glucose levels, and systemic inflammation and improved lipid profiles in patients aged >45 years. BMI, body fat mass, ASM, and waist circumference did not significantly differ between patients in the eradicated group and those in the non-eradicated group.