Purpose: This study aimed to quantitatively evaluate longitudinal changes in drusen area and volume over 36 months in South Korean patients and to identify the factors associated with these changes and the development of advanced age-related macular degeneration (AMD). Methods: In this retrospective study, 38 eyes from 38 patients diagnosed with drusen were analyzed. The drusen area and volume were measured using spectral-domain optical coherence tomography (SD-OCT; Cirrus 5000, Carl Zeiss Meditec) with an automated retinal pigment epithelium elevation map algorithm. To minimize bias from variable follow-up intervals, an annualized classification framework was adopted. Based on percentage change in drusen area within the 5-mm circle, eyes were categorized as progressed (increase >20%), stable (change within ±20%), or regressing (decrease >20%). Results: Both drusen area and volume increased significantly up to 24 months (area, p = 0.003; volume, p = 0.028) and then showed a modest decline at 36 months, remaining above baseline levels. No significant difference in the proportions of progressed, stable, or regressing eyes was observed across 12-month intervals or compared with baseline (all p > 0.05). A larger baseline 5-mm drusen area was significantly associated with the development of advanced AMD (adjusted odds ratio, 2.818; 95% confidence interval, 1.022–7.767; p = 0.045). Eyes that exhibited at least one episode of drusen regression showed a higher incidence of advanced AMD (36.8% vs. 5.3%, p = 0.042). Conclusions Drusen in South Korean patients demonstrated dynamic morphological remodeling over time. Drusen regression was not a benign phenomenon but rather a potential high-risk marker for progression to advanced AMD. These findings highlight the importance of population-specific, quantitative SD-OCT monitoring for early risk stratification in East Asian eyes.

Alzheimer’s disease (AD) is characterized by progressive cognitive deterioration and significant depression. However, the mechanisms linking depression to AD pathology remain unclear. Here, we investigated whether Notch2 signaling mediates depressionlike behaviors in presenilin-2 (PS2) N141I mutant mice, an early-onset AD model. PS2 wild-type (WT) and mutant (MT) mice aged 12-15 months were subjected to unpredictable chronic mild stress (UCMS) for 4 weeks, followed by sucrose preference, tail-hanging, and forced swimming tests. Behavioral assessments showed that UCMS exacerbated anhedonia and immobility only in PS2 MT mice. Molecular analysis revealed concomitant increases in plasma corticosterone, hippocampal γ-secretase activity, and Notch2 expression, and elevated total and phosphorylated glucocorticoid receptor levels in PS2 MT-UCMS mice. Gene expression profiling of human hippocampal datasets confirmed upregulation of NOTCH2 in Alzheimer’s disease and depression.Pharmacological inhibition of γ-secretase and Notch signaling with DAPT normalizes depressive behavior, reduces corticosterone release, attenuates GR phosphorylation, and inhibits Notch2 signaling in PS2 MT mice. These findings identify Notch2 as a pivotal mediator linking chronic stress to molecular changes associated with depression and AD, and suggest that targeting Notch2 signaling may provide therapeutic benefits for comorbid mood and neurodegenerative disorders.

Although aspartate aminotransferase (AST) is a serum marker of hepatocellular damage in chronic hepatitis, it is difficult to interpret very high AST levels with concurrent low alanine aminotransferase (ALT) levels. Macro-AST is an immunoglobulin-AST complex that can present as aberrant high enzymatic activity without significant inflammation in the liver. Two patients with chronic hepatitis B presented with disproportionate AST elevations. Their plasma samples were precipitated with polyethylene glycol (PEG) and stored at 4°C for macro-AST determinations. In Case 1, PEG precipitation showed 100% removal of AST activity, and refrigerated storage resulted in a ~70% decline over seven days, confirming macro-AST. In Case 2, both tests showed minimal changes, suggesting that macro-AST was unlikely. The AST levels normalized after antiviral therapy, suggesting immune-active hepatitis as the probable cause, but the other contributing factors could not be completely excluded. The abrupt decrease in AST activity after PEG precipitation and during refrigeration storage suggests that relatively high AST values compared to ALT might be attributed to the presence of macro-AST.These non-invasive methods for detecting macroenzymes might help the patient avoid unnecessary further work-ups.

Background and Objectives: Hearing loss significantly affects communication, psychosocial well-being, and quality of life. This study analyzes the National Health Insurance Service database to assess the trends and characteristics of hearing loss in South Korea from 2010 to 2020.Subjects and Method The database encompasses 97% of the Korean population, providing comprehensive data on medical history, prescriptions, and health examinations. The analysis used the World Health Organization’s ICD-10 definitions to categorize hearing loss types and examine their prevalence and incidence across various demographics over 11 years. Results: There was an overall annual increase of 4.62% in diagnosed cases of hearing loss, with the most significant rise among the elderly. The rate of increase accelerated from 3.32% between 2010 and 2014 to 6.49% between 2014 and 2020, corresponding with the improved hearing aid access facilitated by policy changes. Women showed a slightly higher increase than men. The data also indicated a consistent rise in abnormal hearing test results during health examinations, especially in older adults. Conclusion The study highlights an increasing trend in hearing loss diagnoses, driven by an aging population and enhanced detection facilitated by policy changes. These findings emphasize the need for continuous monitoring and targeted health policies to manage hearing loss effectively, offering valuable insights for global health management and policy development.

Background and Objectives: This study aims to analyze trends in hearing disability and the use of hearing rehabilitation devices (hearing aids and cochlear implants) in South Korea over the past 11 years (2010-2020) using data from the National Health Insurance Service (NHIS).Subjects and Method Data were extracted from the NHIS database, covering approximately 97% of the South Korean population. Patients diagnosed with hearing loss were classified using ICD-10 codes. The data were analyzed to determine trends in hearing disability, hearing aid prescriptions, and cochlear implant usage by age, gender, and types and causes of hearing loss. Results: The number of hearing disability patients increased from 170900 in 2010 to 362738 in 2020, with an annual growth rate of 7.95%. The highest increase was observed in the ≥60 age group, with an annual growth rate of 11.04%. Hearing aid prescriptions rose from 4966 in 2010 to 11974 in 2020, showing a 10.45% annual increase. Females showed a higher growth rate in both hearing disability and hearing aid prescriptions compared to males. Cochlear implant prescriptions also increased, particularly among older adults. Conclusion The study highlights a significant rise in hearing disability and the use of hearing aids and cochlear implants in South Korea, especially among the elderly. The findings underscore the importance of early diagnosis and intervention for hearing loss and the need for policy improvements to enhance accessibility and affordability of hearing rehabilitation services. Additional strategies are needed to ensure appropriate hearing rehabilitation for those not yet receiving adequate care.

Objective: To prospectively evaluate the effect of accelerated deep learning-based reconstruction (Accel-DL) on improving brain magnetic resonance imaging (MRI) quality and reducing scan time compared to that in conventional MRI. Materials and Methods: This study included 150 participants (51 male; mean age 57.3 ± 16.2 years). Each group of 50 participants was scanned using one of three 3T scanners from three different vendors. Conventional and Accel-DL MRI images were obtained from each participant and compared using 2D T1- and T2-weighted and 3D gradient-echo sequences. Accel-DL acquisition was achieved using optimized scan parameters to reduce the scan time, with the acquired images reconstructed using U-Net-based software to transform low-quality, undersampled k-space data into high-quality images. The scan times of Accel-DL and conventional MRI methods were compared. Four neuroradiologists assessed the overall image quality, structural delineation, and artifacts using Likert scale (5- and 3-point scales). Inter-reader agreement was assessed using Fleiss’ kappa coefficient. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated, and volumetric quantification of regional structures and white matter hyperintensities (WMHs) was performed. Results: Accel-DL showed a mean scan time reduction of 39.4% (range, 24.2%–51.3%). Accel-DL improved overall image quality (3.78 ± 0.71 vs. 3.36 ± 0.61, P < 0.001), structure delineation (2.47 ± 0.61 vs. 2.35 ± 0.62, P < 0.001), and artifacts (3.73 ± 0.72 vs. 3.71 ± 0.69, P = 0.016). Inter-reader agreement was fair to substantial (κ = 0.34–0.50). SNR and CNR increased in Accel-DL (82.0 ± 23.1 vs. 31.4 ± 10.8, P = 0.02; 12.4 ± 4.1 vs. 4.4 ± 11.2, P = 0.02). Bland-Altman plots revealed no significant differences in the volumetric measurements of 98.2% of the relevant regions, except in the deep gray matter, including the thalamus. Five of the six lesion categories showed no significant differences in WMH segmentation, except for leukocortical lesions (r = 0.64 ± 0.29). Conclusion Accel-DL substantially reduced the scan time and improved the quality of brain MRI in both spin-echo and gradientecho sequences without compromising volumetry, including lesion quantification.

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.

Background and Objectives: Obstructive sleep apnea (OSA) has been associated with an increased risk of cancer in various organs. OSA is also linked to chronic inflammation in the biliary tract and pancreas, a well-established risk factor for carcinogenesis in these organs. However, its relationship with biliary tract and pancreatic cancers remains unclear and has been rarely investigated. Therefore, we aimed to evaluate whether OSA serves as an independent risk factor for these malignancies by analyzing a nationwide healthcare claims database in South Korea. Methods: A retrospective cohort study was conducted using the Korean National Health Insurance Service (KNHIS) database. Adults aged ≥20 years who were newly diagnosed with OSA (ICD-10: G47.30) between 2007 and 2014 were identified and propensity score-matched (1:5) with controls based on age, sex, and comorbidities. Individuals with pre-existing cancer diagnoses were excluded. The primary endpoints were the incidence of overall cancer, biliary tract cancer (C23–C24), and pancreatic cancer (C25). Cox proportional hazards regression models were used to calculate hazard ratios (HRs), adjusting for demographic and clinical factors. Results: A total of 1,191,444 individuals were included, comprising 198,574 patients diagnosed with OSA and 992,870 matched controls. OSA was associated with an increased overall cancer incidence (HR, 1.132; 95% confidence interval [CI], 1.097–1.169); however, it was not significantly associated with pancreatic cancer (HR, 0.941; 95% CI, 0.823–1.072) or biliary tract cancer (HR, 0.931; 95% CI, 0.751–1.142). Subgroup analyses stratified by sex and age revealed no statistically significant associations across these groups. Conclusion Our findings do not support OSA as an independent risk factor for biliary tract or pancreatic cancers.

Background: and Purpose Previous research on patients with acute ischemic stroke (AIS) has shown a 0.5% incidence of major gastrointestinal bleeding (GIB) requiring blood transfusion during hospitalization. The existing literature has insufficiently explored the long-term incidence in this population despite the decremental impact of GIB on stroke outcomes. Methods: We analyzed the data from a cohort of patients with AIS admitted to 14 hospitals as part of a nationwide multicenter prospective stroke registry between 2011 and 2013. These patients were followed up for up to 6 years. The occurrence of major GIB events, defined as GIB necessitating at least two units of blood transfusion, was tracked using the National Health Insurance Service claims data. Results: Among 10,818 patients with AIS (male, 59%; mean age, 68±13 years), 947 (8.8%) experienced 1,224 episodes of major GIB over a median follow-up duration of 3.1 years. Remarkably, 20% of 947 patients experienced multiple episodes of major GIB. The incidence peaked in the first month after AIS, reaching 19.2 per 100 person-years, and gradually decreased to approximately one-sixth of this rate by the 2nd year with subsequent stabilization. Multivariable analysis identified the following predictors of major GIB: anemia, estimated glomerular filtration rate <60 mL/min/1.73 m2 , and a 3-month modified Rankin Scale score of ≥4. Conclusion Patients with AIS are susceptible to major GIB, particularly in the first month after the onset of AIS, with the risk decreasing thereafter. Implementing preventive strategies may be important, especially for patients with anemia and impaired renal function at stroke onset and those with a disabling stroke.

Background: Complete revascularization has demonstrated better outcomes in patients with acute myocardial infarction (AMI) and multivessel disease. However, in the case of left main (LM) culprit lesion AMI with multivessel disease, there is limited evidence to suggest that complete revascularization is better. Methods: We reviewed 16,831 patients in the Korea Acute Myocardial Infarction Registry who were treated from July 2016 to June 2020, and 399 patients were enrolled with LM culprit lesion AMI treated with percutaneous coronary intervention. We categorized the patients as those treated with complete revascularization (n=295) or incomplete revascularization (n=104). The study endpoint was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause death, myocardial infarction, ischemia-driven revascularization, stent thrombosis, and stroke. We performed propensity score matching (PSM) and analyzed the incidence of MACCE at 1 year. Results: After PSM, the two groups were well balanced. There was no significant difference between the two groups in MACCE at 1 year (12.1% vs. 15.2%; hazard ratio, 1.28; 95% confidence interval, 0.60–2.74; p=0.524) after PSM. The components of MACCE and major bleeding were also not significantly different. Conclusion There was no significant difference in clinical outcomes between the groups treated with complete or incomplete revascularization for LM culprit lesion AMI with multivessel disease.