Background: Transthyretin amyloidosis, a protein-misfolding disorder characterized by systemic amyloid deposition, can be classified as wild-type transthyretin amyloidosis (ATTRwt) or hereditary transthyretin amyloidosis (ATTRv), depending on the presence of transthyretin (TTR) gene variants. We examined the genetic distribution of TTR variants in Korean patients diagnosed with ATTRv. Methods: We retrospectively reviewed 801 participants who underwent TTR analysis at Samsung Medical Center from 2012 to 2024. The participants were categorized into two groups: in-house probands or relatives, and externally referred probands or relatives. Results: Pathogenic or likely pathogenic TTR variants were detected in 36 of 165 in-house probands (21.8%), among which D38A was the most frequent variant (50.0%; 18/36), followed by M13dup and E89K (8.3% each). Among referred probands, D38A was predominant (54.5%; 12/22), followed by M13dup (22.7%; 5/22). Cardiac amyloid involvement was the most common manifestation, observed in 97.2% (35/36) of in-house probands with ATTRv, followed by peripheral nervous system (PNS; 94.4%) and autonomic nervous system (ANS; 88.9%) involvement. In contrast, ANS involvement was most prevalent among in-house relatives who underwent organ evaluation (61.5%; 24/39), followed by cardiac (52.1%; 25/48) and PNS (48.7%; 19/39) involvement. Five of the eight in-house relatives harboring M13dup (62.5%) showed organ involvement, primarily in the ANS, supporting the pathogenicity of this variant. Conclusions This study provides the largest single-institution dataset of Korean patients with ATTRv, incorporating systematic organ assessments. The predominance of the unique TTR variants D38A and M13dup delineates a distinct genetic landscape that may facilitate accurate and timely diagnosis of ATTRv in the Korean population.

Purpose: Esophagojejunal anastomotic leakage (EJAL) represents a severe postoperative complication following total or proximal gastrectomy. Treatment strategies include conservative management, endoscopic interventions, and surgery; however, comparative data remain limited. This study aimed to compare clinical outcomes of different strategies to identify the optimal approach based on anastomotic defect size. Materials and Methods: This retrospective study reviewed 100 patients diagnosed with EJAL between January 2015 and October 2024. Patients were categorized into four groups:conservative management, endoscopic vacuum-assisted closure (E-VAC), other endoscopic treatments, and surgery. The primary outcomes were leakage duration and length of hospital stay after EJAL diagnosis, whereas the secondary outcome was time to C-reactive protein normalization. Subgroup analyses were performed according to defect size. Results: Among the 100 patients, 76 were male and 24 were female, with a mean age of 65.7 years. Conservative treatment was the most common modality (53%), followed by other endoscopic treatments (19%), E-VAC (14%), and surgery (14%). In patients with a defect size <1 cm, conservative treatment was associated with significantly shorter leakage duration (P=0.035) and earlier resumption of diet (P=0.029) compared with endoscopic treatment.Among those with defects ≥2 cm, E-VAC demonstrated the most favorable median outcomes across all variables; however, statistical significance was not achieved because of the small sample size. Conclusions Conservative treatment appears to be the most effective treatment strategy for EJAL with anastomotic defects <1 cm. For larger defects (≥2 cm), E-VAC may offer clinical benefit, although further studies are needed to confirm its efficacy. These findings highlight the importance of individualized treatment selection based on defect size.

Objectives: This study investigated how the mediating effect of health literacy (HL) on the association between income and cancer screening participation varies by age among Korean adults aged 40 years and older, with the aim of identifying the optimal timing for HL interventions. Methods: Data from 4171 adults aged ≥40 years in the 2023 Korea National Health and Nutrition Examination Survey were analyzed using moderated mediation analysis implemented with the lavaan.survey package, accounting for the complex sampling design. The Johnson–Neyman technique was used to identify age thresholds at which the mediation effect became statistically significant, and the number needed to benefit (NNB) was calculated to estimate the potential efficiency of interventions targeting this pathway. Results: Each 1-quintile increase in income was associated with a 16.0% higher likelihood of undergoing cancer screening (odds ratio=1.16, p<0.001). The mediating effect of HL increased significantly with age (index of moderated mediation=0.000438, p=0.048). Mediation became statistically significant from age 54.2 years (Johnson–Neyman threshold), with the proportion of the total effect mediated rising from 0.1% among adults aged 40–49 years to 8.1% among those aged ≥70 years. The NNB for this pathway indicated substantial intervention efficiency in older adults (NNB=372 for ages ≥70), whereas the mediation effect was not statistically significant in the 50–59 age group. Conclusions HL significantly mediated the relationship between income and cancer screening participation from the mid-50s onward, with progressively greater contributions at older ages. These findings support age-differentiated strategies, including structural accessibility improvements for adults in their 40s and early 50s and integrated income–HL interventions for individuals aged ≥55 years. Experimental studies are warranted to confirm these associations.

Purpose: We investigated the antiadhesive effects of lidocaine, methylene blue, and atorvastatin, with a focus on preventing remote adhesions in a rat model of postoperative adhesions. Methods: Models were assigned to either the control group (saline infusion only) or treatment groups (group L, lidocaine;group M, methylene blue; or group S, atorvastatin). Adhesions were induced by intestinal or abdominal wall injuries. The rats were sacrificed 2 weeks after surgery. Results: The number of remote adhesions was markedly lower in groups L, M, and S than in the control group. The macroscopic adhesion score was substantially lower in groups L, M, and S than in the control group. Acute and chronic inflammation, as well as fibrosis scores, were also markedly lower in groups L, M, and S than in the control group. IL-1βlevels were considerably reduced in groups L, M, and S at 2 hours after surgery and remained substantially lower in group S at 48 hours. IL-6 levels were markedly reduced in groups M and S at 2 hours and in all treatment groups at 48 hours than in the control group. Conclusion Intraperitoneal administration of lidocaine, methylene blue, and atorvastatin effectively reduced remote adhesion formation, macroscopic and microscopic adhesion scores, and inflammatory cytokine levels in a rat adhesion model.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine that selectively targets cancer cells and induces apoptosis. However, many cancers, including bladder cancer, develop resistance to TRAIL, limiting the efficacy of TRAIL-based therapies. This study investigated whether betulinic acid (BA), a pentacyclic triterpenoid with anticancer and chemosensitizing properties, increases TRAIL-mediated apoptosis in TRAIL-resistant human bladder cancer cells. Combination treatment with BA and TRAIL significantly increased cytotoxicity and apoptosis compared to either treatment alone. This combination treatment also increased reactive oxygen species (ROS) production, increased Bax expression and Bid cleavage (tBid formation), and downregulated Bcl-2 levels. These effects were accompanied by caspase activation via extrinsic and intrinsic pathways, leading to cytochrome c release via mitochondrial membrane destabilization, thereby contributing to increased apoptosis. Furthermore, the combination treatment inhibited phosphoinositide 3-kinase (PI3K) and Akt phosphorylation; this effect was amplified by a PI3K inhibitor but abrogated by ROS inhibition. Collectively, our results suggest that BA sensitizes bladder cancer cells to TRAILinduced apoptosis via ROS-dependent activation of the apoptotic pathway and inhibition of PI3K/Akt signaling. Therefore, the BA and TRAIL combination exhibits potential to overcome TRAIL resistance in human bladder cancer.

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.

Purpose: This study aimed to evaluate the role of hepatic resection in patients with objective responses after combined transarterial chemoembolization (TACE) and radiotherapy (RT) for hepatocellular carcinoma (HCC) with macroscopic vascular invasion (MVI). Materials and Methods: We retrospectively reviewed the patients treated with combined TACE and RT for HCC with MVI between 2010 and 2015. Some of the patients with objective responses underwent hepatic resection or liver transplantation; to investigate the impact of surgery, patients with objective responses who did not undergo surgery were selected as the control group. Survival outcomes were compared using a propensity score–based stabilized inverse probability of treatment weighting method. Results: Out of the 170 patients with objective responses after combined TACE and RT, 41 patients underwent surgery, including eight liver transplantations. The unweighted surgery group was younger and had a higher proportion of solitary tumors and unilateral vascular involvement. After adjustment, the 3-year overall survival (OS) rates were 61.0% and 28.6% in the surgery and non-surgery groups, respectively. The most important prognostic factor for OS was surgery (adjusted Cox hazard ratio [HR], 0.28; 95% confidence interval [CI], 0.17 to 0.46; p < 0.001). Complete response after TACE and RT (vs. partial response) was also a significant prognostic factor for OS (adjusted HR, 0.41; 95% CI, 0.27 to 0.61; p < 0.001). There was no surgical mortality. Four patients (9.8%) required additional surgery due to bleeding or graft failure. Conclusion Hepatic resection was significantly associated with improved OS in patients who showed objective responses after receiving combined TACE and RT for HCC with MVI.

Objectives: . Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder that is strongly influenced by obesity, the most important modifiable risk factor. Effective weight management is therefore essential for optimal OSA care. This guideline provides updated, evidence-based recommendations for the evaluation and management of obesity in adults with OSA, incorporating recent advances in lifestyle, pharmacologic, and surgical interventions. Methods: . The Korean Society of Sleep and Breathing convened a multidisciplinary panel. A systematic literature search was performed across major databases through 2025. Evidence was appraised using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, and recommendations were formulated by consensus using the Evidence-to-Decision framework. Results: . Eight statements were developed. Key recommendations include recognizing obesity as a major risk factor; routinely assessing overweight and obesity; and implementing structured weight reduction through diet, exercise, and behavioral therapy. Glucagon-like peptide-1 receptor agonists are recommended when lifestyle interventions are insufficient, and bariatric/metabolic surgery is advised for severe obesity unresponsive to nonsurgical treatment. Weight loss improves the apnea-hypopnea index, symptoms, and cardiometabolic markers and may reduce positive airway pressure needs. Continued follow-up is recommended even after clinical improvement. Conclusion . Weight management is a core component of OSA treatment. This guideline offers practical, evidence-based strategies to support clinicians in delivering effective, obesity-focused care for adults with OSA.

Purpose: To develop the 2025 update to the Korean colorectal cancer (CRC) screening guidelines by systematically evaluating recent evidence, integrating domestic data, and addressing changes since the 2015 guideline revision, thereby providing an evidence-based standard for clinicians and policymakers. Methods: A multidisciplinary committee developed the guidelines using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. The process included formulation of three key questions addressing screening efficacy, diagnostic accuracy, and optimal screening age and interval. A systematic review of international guidelines and primary literature was conducted, yielding 327 eligible studies. In addition, a utility-based analysis using a Markov model was performed to determine optimal screening ages and intervals. Results: The evidence synthesis identified high-certainty evidence supporting the use of the fecal immunochemical test (FIT) for reducing CRC mortality and moderate-certainty evidence for colonoscopy. Evidence for computed tomographic colonography (CTC) and stool DNA testing was rated as very low certainty. Based on the evidence review and cost-utility analysis, the committee conditionally recommends CRC screening for asymptomatic, average-risk adults aged 45–74 years using either colonoscopy every 10 years or FIT every 1–2 years. CTC and stool DNA testing were not recommended owing to insufficient evidence. Conclusion The 2025 Korean Guidelines for Colorectal Cancer Screening present updated, evidence-based recommendations tailored to the domestic healthcare context. By conditionally endorsing both colonoscopy and FIT for individuals aged 45–74 years, these guidelines aim to improve population-level screening effectiveness and reduce the burden of CRC in South Korea.

Background: Cisplatin-based chemotherapy is a mainstay treatment for head and neck squamous cell carcinoma (HNSC); however, resistance to cisplatin contributes substantially to poor clinical outcomes. Identifying biomarkers associated with cisplatin response may improve prognostic assessment and treatment selection. Methods: We retrospectively analyzed The Cancer Genome Atlas (TCGA)-HNSC dataset to evaluate the association between microtubule associated scaffold protein 1 (MTUS1) expression and clinical outcomes, with particular emphasis on patients who were cisplatin-treated. Survival analysis was performed using the Kaplan-Meier curves, and differential expression analysis was conducted separately by comparing patients in disease-specific survival (DSS)-living and DSS-deceased groups. MTUS1 messenger RNA and protein levels were examined in cisplatin-sensitive oral cancer cell lines and their paired cisplatin-resistant counterparts using quantitative reverse transcription polymerase chain reaction and western blotting. Functional relevance was assessed by small interfering RNA-mediated MTUS1 knockdown in primary oral squamous cell carcinoma organoids. Results: MTUS1 protein expression was significantly lower in HNSC tumors than in non-tumor tissues. In the overall TCGA-HNSC cohort, MTUS1 expression was not significantly associated with survival. However, in patients who were cisplatin-treated, higher MTUS1 expression was significantly associated with more favorable DSS. MTUS1 expression was consistently lower in cisplatin-resistant oral cancer cell lines than in their paired cisplatin-sensitive counterparts. Functional experiments further suggested that reduced MTUS1 expression is associated with decreased cisplatin sensitivity and a resistant phenotype. Conclusion MTUS1 expression may be associated with clinical outcomes in patients with cisplatin-treated HNSC and is related to cisplatin responsiveness. These findings suggest a role for MTUS1 as a candidate treatment-relevant biomarker and highlight the value of integrating public omics data with experimental validation.