Fine particulate matter (FPM) is a major component of air pollution and has emerged as a significant global health concern owing to its adverse health effects. Previous studies have investigated the correlation between bone health and FPM through cohort or review studies. However, the effects of FPM exposure on bone health are poorly understood. This study aimed to investigate the effects of FPM on bone health and elucidate these effects in vitro and in vivo using mice. Micro-CT analysis in vivo revealed FPM exposure decreased bone mineral density, trabecular bone volume/total volume ratio, and trabecular number in the femurs of mice, while increasing trabecular separation. Histological analysis showed that the FPM-treated group had a reduced trabecular area and an increased number of osteoclasts in the bone tissue. Moreover, in vitro studies revealed that low concentrations of FPM significantly enhanced osteoclast differentiation. These findings further support the notion that short-term FPM exposure negatively impacts bone health, providing a foundation for further research on this topic.

Background: High-resolution chest computed tomography (CT) is a crucial assessment tool for diagnosing Birt-Hogg-Dubé (BHD) syndrome. This study aimed to analyze differences of lung cysts between BHD and other cystic lung diseases. Methods: From January 2020 to December 2022, patients with multiple lung cysts who underwent chest CT at Gangnam Severance Hospital were included. Results: Over a 3-year period (from January 2020 to December 2022), out of 52,823 patients who underwent a chest CT scan, 301 (0.6%) patients with multiple lung cysts were enrolled in this study. Of enrolled patients, 24 (8.0%) were diagnosed with BHD. In patients with BHD, 95.8% exhibited bilateral cysts, and 83.3% showed basal predominance. The cysts’ maximal diameter averaged 32.1 mm (interquartile range, 26.5 to 43.5). Additionally, 95.8% of patients with BHD had diverse cyst sizes and morphologies. Multivariate logistic regression analysis revealed that bilateral cysts (odds ratio [OR], 12.393; 95% confidence interval [CI], 1.613 to 274.682; p=0.038), basal predominance (OR, 8.511; 95% CI, 2.252 to 39.392; p=0.002), maximum diameter (OR, 1.053; 95% CI, 1.009 to 1.108; p=0.032), and diversity of morphology (OR, 19.513; 95% CI, 2.833 to 398.119; p=0.010) were significant factors associated with BHD diagnosis. A multivariate prediction model for BHD diagnosis demonstrated a sensitivity of 95.83%, a specificity of 81.22%, and an area under the receiver operating characteristic curve of 0.951 (95% CI, 0.914 to 0.987). Conclusion Distinguishing features of lung cysts from other cystic lung diseases include bilateral cysts, basal dominance, large size, and irregular shape.

Background: The development of frailty at hospital discharge affects the clinical outcomes in severe coronavirus disease 2019 (COVID-19) survivors who had no frailty before hospitalization. We aimed to describe the prevalence of new frailty using the clinical frailty scale (CFS) and evaluate its associated factors in patients with severe COVID-19 without pre-existing frailty before hospitalization. Methods: We performed a secondary analysis of clinical data from a nationwide retrospective cohort collected from 22 hospitals between January 1, 2020 and August 31, 2021. The patients were at least 19 years old and survived until discharge after admission to the intensive care unit (ICU) because of severe COVID-19. Development of new frailty was defined as a CFS score ≥5 at hospital discharge. Results: Among 669 severe COVID-19 survivors without pre-existing frailty admitted to the ICU, the mean age was 65.2±12.8 years, 62.5% were male, and 50.2% received mechanical ventilation (MV). The mean CFS score at admission was 2.4±0.9, and new frailty developed in 27.8% (186/483). In multivariate analysis, older age, cardiovascular disease, CFS score of 3–4 before hospitalization, increased C-reactive protein level, longer duration of corticosteroid treatment, and use of MV and extracorporeal membrane oxygenation were identified as factors associated with new-onset frailty. Conclusion Our study suggests that new frailty is not uncommon and is associated with diverse factors in survivors of severe COVID-19 without pre-existing frailty.

Background: Kelch-like ECH-associated protein 1 (KEAP1)–nuclear factor erythroid- 2-related factor 2 (NRF2) pathway is a major regulator protecting cells from oxidative and metabolic stress. Studies have revealed that this pathway is involved in mediating resistance to cytotoxic chemotherapy and immunotherapy; however, its implications in oncogene-addicted tumors are largely unknown. This study aimed to elucidate whether this pathway could be a potential therapeutic target for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer. Methods: We measured the baseline expression of NRF2 using EGFR-mutant parental cells and acquired gefitinib resistant cells. We investigated whether NRF2 inhibition affected cell death in vitro and tumor growth in vivo using a xenograft mouse model, and compared the transcriptional changes before and after NRF2 inhibition. Results: Baseline NRF2 expression was enhanced in PC9 and PC9 with gefitinib resistance (PC9/GR) cells than in other cell lines, with a more prominent expression in PC9/ GR. The NRF2 inhibitor induced NRF2 downregulation and cell death in a dose-dependent manner. Cotreatment with an NRF2 inhibitor enhanced osimertinib-induced cell death in vitro, and potentiated tumor growth inhibition in a PC9/GR xenograft model. Finally, RNA sequencing revealed that NRF2 inhibition resulted in the altered expression of multiple genes involved in various signaling pathways. Conclusion We identified that NRF2 inhibition enhanced cell death and inhibited tumor growth in tyrosine kinase inhibitor (TKI)-resistant lung cancer with EGFR-mutation. Thus, NRF2 modulation may be a novel therapeutic strategy to overcome the resistance to EGFR-TKIs.

Purpose: This study evaluated the educational impact of an artificial intelligence (AI)–based decision support system for breast ultrasonography (US) on medical professionals not specialized in breast imaging. Methods: In this multi-case, multi-reader study, educational materials, including American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) descriptors, were provided alongside corresponding AI results during training. The AI system presented results in the form of AIheatmaps, AI scores, and AI-provided BI-RADS assessment categories. Forty-two readers evaluated the test set in three sessions: the first session (S1) occurred before the educational intervention, the second session (S2) followed education without AI assistance, and the third session (S3) took place after education with AI assistance. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and overall performance, were compared between the sessions. Results: The mean sensitivity increased from 66.5% (95% confidence interval [CI], 59.2% to 73.7%) to 88.7% (95% CI, 84.1% to 93.3%), with a statistically significant difference (P<0.001), and the AUC non-significantly increased from 0.664 (95% CI, 0.606 to 0.723) to 0.684 (95% CI, 0.620 to 0.748) (P=0.300). Both measures were higher in S2 than in S1. The AI-achieved AUC was comparable to that of the expert reader (0.747 [95% CI, 0.640 to 0.855] vs. 0.803 [95% CI, 0.706 to 0.900], P=0.217). Additionally, with AI assistance, the mean AUC for inexperienced readers was not significantly different from that of the expert reader (0.745 [95% CI, 0.660 to 0.830] vs. 0.803 [95% CI, 0.706 to 0.900], P=0.120). Conclusion The mean AUC and sensitivity improved after incorporating AI into breast US education and interpretation. AI systems with high-level performance for breast US can potentially be used as educational tools in the interpretation of breast US images.

Background: s/Aims: Hepatocellular carcinoma (HCC) is the sixth most common cancer and second leading cause of cancer-related deaths in South Korea. This study evaluated the characteristics of Korean patients newly diagnosed with HCC in 2016-2018. Methods: Data from the Korean Primary Liver Cancer Registry (KPLCR), a representative database of patients newly diagnosed with HCC in South Korea, were analyzed. This study investigated 4,462 patients with HCC registered in the KPLCR in 2016-2018. Results: The median patient age was 63 years (interquartile range, 55-72). 79.7% of patients were male. Hepatitis B infection was the most common underlying liver disease (54.5%). The Barcelona Clinic Liver Cancer (BCLC) staging system classified patients as follows: stage 0 (14.9%), A (28.8%), B (7.5%), C (39.0%), and D (9.8%). The median overall survival was 3.72 years (95% confidence interval, 3.47-4.14), with 1-, 3-, and 5-year overall survival rates of 71.3%, 54.1%, and 44.3%, respectively. In 2016-2018, there was a significant shift toward BCLC stage 0-A and Child-Turcotte-Pugh liver function class A (P<0.05), although survival rates did not differ by diagnosis year. In the treatment group (n=4,389), the most common initial treatments were transarterial therapy (31.7%), surgical resection (24.9%), best supportive care (18.9%), and local ablation therapy (10.5%). Conclusions Between 2016 and 2018, HCC tended to be diagnosed at earlier stages, with better liver function in later years. However, since approximately half of the patients remained diagnosed at an advanced stage, more rigorous and optimized HCC screening strategies should be implemented.

Background/Aims: Fexuprazan, a novel potassium-competitive acid blocker, was developed for treating acid-related disorders. Pharmacokinetic and pharmacodynamic properties of fexuprazan, unlike those of proton pump inhibitors, are independent of food effect. This study aims to evaluate differences in efficacy and safety of fexuprazan in patients with erosive esophagitis (EE) according to the timing of dosing. Methods: In this multicenter, open-label noninferiority study, patients who had typical reflux symptoms with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg daily 30 minutes before or after meal. Treatment was completed after 2 weeks or 4 weeks when healing was endoscopically confirmed. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy up to week 4. Safety endpoints included treatment-emergent adverse events (TEAEs). Results: In the prior-to-meal group (n = 89) and after-meal group (n = 86), 4-week EE healing rates were 98.77% and 100.00% (difference, 0.01%; 95% CI, –0.01% to 0.04%) and 2-week EE healing rates were 95.77% and 97.14% (difference, 0.01%; 95% CI, –0.05% to 0.07%), respectively. TEAEs were 9.78% and 8.70% in the prior-to-meal group and the after-meal group, respectively. Conclusions Non-inferiority analysis revealed that taking fexuprazan after meal was non-inferior to taking fexuprazan before meals in patients with EE. The frequency of adverse events was similar between the 2 study groups. The drug is safe and effective for healing EE regardless of the timing of dosing.

Purpose: This study aimed to project cancer incidence and mortality for 2025 to estimate Korea’s current cancer burden. Materials and Methods: Cancer incidence data from 1999 to 2022 were obtained from the Korea National Cancer Incidence Database, while cancer mortality data from 1993 to 2023 were acquired from Statistics Korea. Cancer incidence and mortality were projected by fitting a linear regression model to observed age-specific cancer rates against their respective years and then by multiplying the projected age-specific rates by the anticipated age-specific population for 2025. A joinpoint regression model was applied to identify significant changes in trends, using only the most recent trend data for predictions. Results: A total of 304,754 new cancer cases and 84,019 cancer deaths are expected in Korea in 2025. The most commonly diagnosed cancer is projected to be thyroid cancer, followed by the colorectal, lung, breast, prostate and stomach cancers. These six cancers are expected to account for 63.8% of the total cancer burden. Lung cancer is expected to be the leading cause of cancer-related deaths, followed by liver, colorectal, pancreatic, stomach, and gallbladder cancers, together comprising 66.6% of total cancer deaths. Conclusion The increasing incidence of female breast cancer and the rise in prostate and pancreatic cancers are expected to continue. As aging accelerates, cancer commonly found in older adults are projected to rise significantly.

Purpose: The current study provides national cancer statistics and their secular trends in Korea, including incidence, mortality, survival, and prevalence in 2022, with international comparisons. Materials and Methods: Cancer incidence, survival, and prevalence rates were calculated using the Korea National Cancer Incidence Database (1999-2022), with survival follow-up until December 31, 2023. Mortality data obtained from Statistics Korea, while international comparisons were based on GLOBOCAN data. Results: In 2022, 282,047 newly diagnosed cancer cases (age-standardized rate [ASR], 287.0 per 100,000) and 83,378 deaths from cancer (ASR, 65.7 per 100,000) were reported. The proportion of localized-stage cancers increased from 45.6% in 2005 to 50.9% in 2022. Stomach, colorectal, and breast cancer showed increased localized-stage diagnoses by 18.1, 18.5, and 9.9 percentage points, respectively. Compared to 2001-2005, the 5-year relative survival (2018-2022) increased by 20.4 percentage points for stomach cancer, 7.6 for colorectal cancer, and 5.6 for breast cancer. Korea had the lowest cancer mortality among countries with similar incidence rates and the lowest mortality-to-incidence (M/I) ratios for these cancers. The 5-year relative survival (2018-2022) was 72.9%, contributing to over 2.59 million prevalent cases in 2022. Conclusion Since the launch of the National Cancer Screening Program in 2002, early detection has improved, increasing the diagnosis of localized-stage cancers and survival rates. Korea recorded the lowest M/I ratio among major comparison countries, demonstrating the effectiveness of its National Cancer Control Program.

Purpose: This multicenter, open-label, phase II trial evaluated the efficacy and safety of bortezomib combined with dexamethasone for the treatment of relapsed/refractory cutaneous T-cell lymphoma (CTCL) in previously treated patients across 14 institutions in South Korea. Materials and Methods: Between September 2017 and July 2020, 29 patients with histologically confirmed CTCL received treatment, consisting of eight 4-week cycles of induction therapy followed by maintenance therapy, contingent upon response, for up to one year. The primary endpoint was the proportion of patients achieving an objective global response. Results: Thirteen of the 29 patients (44.8%) achieved an objective global response, including two complete responses. The median progression-free survival (PFS) was 5.8 months, with responders showing a median PFS of 14.0 months. Treatment-emergent adverse events were generally mild, with a low incidence of peripheral neuropathy and hematologic toxicities. Despite the trend toward shorter PFS in patients with higher mutation burdens, genomic profiling before and after treatment showed no significant emergence of new mutations indicative of disease progression. Conclusion This study supports the use of bortezomib and dexamethasone as a viable and safe treatment option for previously treated CTCL, demonstrating substantial efficacy and manageability in adverse effects. Further research with a larger cohort is suggested to validate these findings and explore the prognostic value of mutation profiles.