Background: DNA methylation is under investigation as an early diagnostic biomarker for cancers such as hepatocellular carcinoma (HCC). p21-activated protein kinase 1 (PAK1) demonstrates a high methylation tendency in HCC. We assessed the diagnostic and prognostic performance of PAK1 methylation in liver transplantation (LT) recipients with and without HCC. Methods: To assess PAK1 methylation, stored pretransplant blood samples from LT recipients were analyzed by droplet digital polymerase chain reaction. Results: This study included 274 patients with HCC and 100 control patients without the disease. Ten-year survival rates in the HCC and control groups were 60.5% and 80.6%, respectively (P=0.001). The 10-year HCC recurrence rate was 39.0%. Ten-year survival rates in the HCC recurrence and nonrecurrence groups were 13.3% and 91.2%, respectively (P<0.001); median PAK1 methylation levels in the control and HCC groups were 50.0 and 108.0 copies (P=0.102). The area under the receiver operating characteristic curve was 0.599, and the Youden J index was 0.199, indicating 57.9% sensitivity and 62.0% specificity at a cutoff of 78 copies. With a cutoff of 5 copies, sensitivity was 94.1% and specificity was 14.0%. The positive likelihood ratio was 1.09 and the negative likelihood ratio was 0.42, indicating diagnostic accuracy below α-fetoprotein and protein induced by vitamin K absence or antagonist-II. PAK1 cutoffs of 5 and 10 copies did not affect HCC recurrence, but a cutoff of 2 copies appeared associated with lower recurrence. Conclusions These data suggest that PAK1 methylation is not a clinically useful biomarker for HCC in LT recipients. New DNA methylation biomarkers are required for early diagnosis.

Anomalous union of the pancreaticobiliary duct (AUPBD) is a congenital malformation in which the pancreatic and biliary ducts join outside the duodenal wall, forming an elongated common channel. Because sphincter action does not directly affect this junction, reciprocal reflux of pancreatic juice and bile occurs, increasing the risk of biliary tract cancer. AUPBD is frequently associated with choledochal cysts and is a known risk factor for biliary malignancies. We report a case of a 70-year-old woman diagnosed with gallbladder cancer with liver metastases, accompanied by AUPBD without choledochal cysts. She presented with upper abdominal pain, obstructive jaundice, and a large hepatic mass on imaging. Endoscopic retrograde cholangiopancreatography confirmed pancreatobiliary-type AUPBD. Despite biliary drainage, her condition rapidly deteriorated and she died soon after. This case underscores the role of AUPBD in carcinogenesis and the need for early recognition and management.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed for their anti-inflammatory and analgesic effects; however, their prolonged use significantly contributes to peptic ulcer disease (PUD) and its complications, such as bleeding and perforation. The pathogenesis primarily involves cyclooxygenase (COX) enzyme inhibition and direct mucosal injury, leading to impaired gastrointestinal defense mechanisms. Multiple risk factors, including advanced age, a history of ulcers, and the concurrent use of anticoagulants or corticosteroids, significantly increase the risk of ulcers and related complications. Global epidemiological studies demonstrate considerable geographical variation in prevalence rates. Despite higher NSAID usage, high-income countries exhibit relatively lower rates, primarily due to well-established preventive strategies. Prevention should be based on careful risk stratification that accounts for both gastrointestinal and cardiovascular factors. Proton pump inhibitors have demonstrated superior efficacy in both prevention and treatment, while selective COX-2 inhibitors offer an alternative strategy, though they require careful cardiovascular risk assessment. The synergistic interaction between NSAID use and Helicobacter pylori infection necessitates testing and eradication, particularly in high-risk patients. NSAID discontinuation remains the primary therapeutic strategy when feasible, with studies showing significantly improved healing rates compared with continued use. Recent advances include the emergence of potassium-competitive acid blockers, which provide rapid and sustained acid suppression, offering promising alternatives for both prevention and treatment. Continued research aimed at optimizing preventive strategies and developing novel therapeutic approaches remains essential for improving clinical outcomes in NSAID-induced PUD.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed for their anti-inflammatory and analgesic effects; however, their prolonged use significantly contributes to peptic ulcer disease (PUD) and its complications, such as bleeding and perforation. The pathogenesis primarily involves cyclooxygenase (COX) enzyme inhibition and direct mucosal injury, leading to impaired gastrointestinal defense mechanisms. Multiple risk factors, including advanced age, a history of ulcers, and the concurrent use of anticoagulants or corticosteroids, significantly increase the risk of ulcers and related complications. Global epidemiological studies demonstrate considerable geographical variation in prevalence rates. Despite higher NSAID usage, high-income countries exhibit relatively lower rates, primarily due to well-established preventive strategies. Prevention should be based on careful risk stratification that accounts for both gastrointestinal and cardiovascular factors. Proton pump inhibitors have demonstrated superior efficacy in both prevention and treatment, while selective COX-2 inhibitors offer an alternative strategy, though they require careful cardiovascular risk assessment. The synergistic interaction between NSAID use and Helicobacter pylori infection necessitates testing and eradication, particularly in high-risk patients. NSAID discontinuation remains the primary therapeutic strategy when feasible, with studies showing significantly improved healing rates compared with continued use. Recent advances include the emergence of potassium-competitive acid blockers, which provide rapid and sustained acid suppression, offering promising alternatives for both prevention and treatment. Continued research aimed at optimizing preventive strategies and developing novel therapeutic approaches remains essential for improving clinical outcomes in NSAID-induced PUD.

Purpose: To investigate the clinical characteristics of South Korean patients with pericentral retinitis pigmentosa (RP) and to identify clinical biomarkers associated with rapid visual acuity decline based on baseline factors. Methods: This retrospective study included 59 eyes of 31 patients diagnosed with pericentral RP. Comprehensive ophthalmological examinations and genetic sequencing were conducted to assess the baseline characteristics. For biomarker analysis, eyes were categorized into two groups based on the annual rate of change in visual acuity. The clinical findings of the two groups were evaluated to identify the biomarkers associated with rapid loss of visual acuity. Results: Patients with pericentral RP in this study exhibited a mean best-corrected visual acuity of 0.17 ± 0.23 in logarithm of the minimum angle of resolution. The visual field test showed annular or semicircular scotoma with relatively preserved periphery and 27 eyes (45.8%) exhibited no macular complications in optical coherence tomography. Genetic analysis identified genes associated with previous typical and pericentral RP studies but also highlighted that many genetic causes of pericentral RP remain unidentified. Of the 55 eyes for which the rate of visual acuity change could be estimated, 18 exhibited an annual decline of ≥10%, whereas 37 showed an annual decline of <10%. Male sex and prolonged b-wave latency on dark-adapted 0.01 electroretinogram correlated with rapid visual acuity decline in the multivariate analysis. Conclusions South Korean patients with pericentral RP exhibited a milder phenotype compared to typical RP patients reported in previous studies. Genetic analysis revealed heterogeneity, with mutations in some genes commonly associated with milder forms of RP. Male sex and prolonged b-wave latency on dark-adapted 0.01 electroretinogram were significant biomarkers for predicting rapid visual acuity decline. Monitoring initial b-wave latency is important for predicting visual decline, particularly in male patients with pericentral RP.

Objective: To test the performance of an artificial intelligence-based computer-aided diagnosis (AI-CAD) designed for fullfield digital mammography (FFDM) when applied to synthetic mammography (SM). Materials and Methods: We analyzed 501 women (mean age, 57 ± 11 years) who underwent preoperative mammography and breast cancer surgery. This cohort consisted of 1002 breasts, comprising 517 with cancer and 485 without. All patients underwent digital breast tomosynthesis (DBT) and FFDM during the preoperative workup. The SM is routinely reconstructed using DBT. Commercial AI-CAD (Lunit Insight MMG, version 1.1.7.2) was retrospectively applied to SM and FFDM to calculate the abnormality scores for each breast. The median abnormality scores were compared for the 517 breasts with cancer using the Wilcoxon signed-rank test. Calibration curves of abnormality scores were evaluated. The discrimination performance was analyzed using the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity using a 10% preset threshold. Sensitivity and specificity were further analyzed according to the mammographic and pathological characteristics.The results of SM and FFDM were compared. Results: AI-CAD demonstrated a significantly lower median abnormality score (71% vs. 96%, P < 0.001) and poorer calibration performance for SM than for FFDM. SM exhibited lower sensitivity (76.2% vs. 82.8%, P < 0.001), higher specificity (95.5% vs.91.8%, P < 0.001), and comparable AUC (0.86 vs. 0.87, P = 0.127) than FFDM. SM showed lower sensitivity than FFDM in asymptomatic breasts, dense breasts, ductal carcinoma in situ, T1, N0, and hormone receptor-positive/human epidermal growth factor receptor 2-negative cancers but showed higher specificity in non-cancerous dense breasts. Conclusion AI-CAD showed lower abnormality scores and reduced calibration performance for SM than for FFDM.Furthermore, the 10% preset threshold resulted in different discrimination performances for the SM. Given these limitations, off-label application of the current AI-CAD to SM should be avoided.

Purpose: To investigate the clinical characteristics of South Korean patients with pericentral retinitis pigmentosa (RP) and to identify clinical biomarkers associated with rapid visual acuity decline based on baseline factors. Methods: This retrospective study included 59 eyes of 31 patients diagnosed with pericentral RP. Comprehensive ophthalmological examinations and genetic sequencing were conducted to assess the baseline characteristics. For biomarker analysis, eyes were categorized into two groups based on the annual rate of change in visual acuity. The clinical findings of the two groups were evaluated to identify the biomarkers associated with rapid loss of visual acuity. Results: Patients with pericentral RP in this study exhibited a mean best-corrected visual acuity of 0.17 ± 0.23 in logarithm of the minimum angle of resolution. The visual field test showed annular or semicircular scotoma with relatively preserved periphery and 27 eyes (45.8%) exhibited no macular complications in optical coherence tomography. Genetic analysis identified genes associated with previous typical and pericentral RP studies but also highlighted that many genetic causes of pericentral RP remain unidentified. Of the 55 eyes for which the rate of visual acuity change could be estimated, 18 exhibited an annual decline of ≥10%, whereas 37 showed an annual decline of <10%. Male sex and prolonged b-wave latency on dark-adapted 0.01 electroretinogram correlated with rapid visual acuity decline in the multivariate analysis. Conclusions South Korean patients with pericentral RP exhibited a milder phenotype compared to typical RP patients reported in previous studies. Genetic analysis revealed heterogeneity, with mutations in some genes commonly associated with milder forms of RP. Male sex and prolonged b-wave latency on dark-adapted 0.01 electroretinogram were significant biomarkers for predicting rapid visual acuity decline. Monitoring initial b-wave latency is important for predicting visual decline, particularly in male patients with pericentral RP.

Background: The relationship between circulating lipid levels and the risk for heart failure (HF) is controversial. We aimed to examine this association, and whether it is modified by the duration of diabetes or treatment regimens in people with type 2 diabetes mellitus. Methods: Individuals (n=2,439,978) who underwent health examinations in 2015 to 2016 were identified from the Korean National Health Information Database. Subjects were categorized according to the duration of diabetes (new-onset, <5, 5–10, or ≥10 years) and number of antidiabetic medications. Incident HF was defined according to the International Classification of Diseases, 10th Revision (ICD-10) code I50 as the primary diagnosis during hospitalization. The risk for HF was estimated using multivariate Cox proportional hazard analysis. Results: During a median follow-up of 4.0 years, 151,624 cases of HF occurred. An inverse association between low-density lipoprotein cholesterol (LDL-C) levels and incident HF was observed in the new-onset diabetes group, with an approximately 25% lower risk in those with LDL-C levels of 100–129, 130–159, and ≥160 mg/dL, compared to those with levels <70 mg/dL. However, J-shaped associations were noted in the long-standing diabetes group, with a 16% higher risk in those with LDL-C level ≥160 mg/dL, compared to those with levels <70 mg/dL. Similar patterns were observed in the relationship between total cholesterol or non-high-density lipoprotein cholesterol and the risk for HF, and when subjects were grouped according to the number of antidiabetic medications instead of diabetes duration. Conclusion Different associations between lipid levels and the risk for HF were noted according to disease progression status among individuals with diabetes.