Background: and Purpose: To assess the long-term effectiveness, safety, and economic viability of recently approved Alzheimer’s disease (AD) therapies, as well as to evaluate the real-world application of novel diagnostics among AD patients with diverse comorbidities, comprehensive real-world data (RWD) analysis is essential. The Korean JOint RegistrY for ALZheimer’s Treatment and Diagnostics (JOY-ALZ) endeavors to create a registry of RWD derived from clinical practice on new diagnostic methods and therapeutic agents for AD introduced in Korea since 2021. Methods: Participants must fulfill all the following: 1) be at least 19 years old; 2) be actively receiving, scheduled to initiate, or undergoing evaluation for any AD disease-modifying treatment; 3) have completed amyloid positron emission tomography or cerebrospinal fluid AD immunoassay (a positive result is not essential for participation); 4) have a clinical classification of cognitively unimpaired, mild cognitive impairment, or probable AD dementia. Data generated during routine care is segmented into a minimum dataset, extended dataset, and research-only dataset requiring extra consent. Assessments encompass clinical, cognitive, functional, neurobehavioral, neuroimaging, and biomarker evaluations, in addition to systematic monitoring of new AD treatments and their safety.Data are collected and monitored at baseline, at semiannual intervals during the initial 2 years, and then annually up to 2034. To date, 46 medical centers will participate in JOY-ALZ. Conclusions JOY-ALZ is expected to promote understanding of the long-term clinical outcomes, safety, and cost-effectiveness of recently introduced diagnostics and treatments for AD, thereby supporting the progress of precision medicine in AD care and diagnosis.

Purpose: We compared short-term clinical outcomes after cataract surgery with implantation of a novel refractive extended depth-of-focus TECNIS PureSee intraocular lens (IOL) between patients with stage 1 epiretinal membrane (ERM)—characterized by a thin membrane over the macula with preserved foveal depression―and those with a normal retina. Methods: This retrospective study included 60 eyes of 60 patients who underwent cataract surgery with implantation of the TECNIS PureSee IOL between January 2024 and January 2025: 30 eyes with stage 1 ERM and 30 eyes with a normal retina. Preoperative characteristics, including age, sex distribution, cataract severity, corrected distance visual acuity (CDVA), and higher-order aberrations, were compared between groups, as were IOL power and target refraction. Postoperative outcomes at 1 month―including CDVA, uncorrected distance, intermediate, and near visual acuity, ocular aberrations, and contrast sensitivity―were evaluated. Results: There were no significant differences in preoperative characteristics, such as age, sex distribution, cataract grade, CDVA, higher-order aberrations, IOL power, or target refraction between the two groups. At 1 month postoperatively, CDVA, uncorrected distance, intermediate, and near visual acuity, higher-order aberrations, and contrast sensitivity exhibited no significant differences between groups. Conclusions In this short-term analysis, the PureSee IOL demonstrated comparable efficacy and safety in cataract patients with stage 1 ERM to those with a normal retina.

Rectal cancer, which accounts for approximately 40% of colorectal cancers, remains a major clinical concern. Recent advances in diagnostic imaging, surgical techniques, radiotherapy, and systemic treatment have steadily improved rectal cancer outcomes. Considering this, the Korean Rectal Cancer Multidisciplinary (KRCM) Committee has aimed to provide clinicians and policymakers with up-to-date, evidence-based clinical practice guidelines to support optimal decision-making, reflecting current evidence, the Korean healthcare context, and patient values and preferences. The Clinical Practice Guidelines for Rectal Cancer version 2.0 were developed through multidisciplinary collaboration with related academic societies, building upon and updating the KRCM Clinical Practice Guidelines version 1.0 (titled “Multidisciplinary guidelines for the management of rectal cancer”). These consensus guidelines of the KRCM were established based on a comprehensive literature review, evidence synthesis, with recommendation development guided by the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology, and consideration of applicability in real-world clinical practice under the national health insurance system. Each recommendation has been presented with its strength and level of evidence.

Background: s/Aims: Phase angle (PhA), as measured by bioelectrical impedance analysis, provides insights into hydration and nutritional status, making it a prognostic indicator of frailty. While low preoperative PhA has been linked to postoperative complications in cancer patients, its predictive value in individuals undergoing pancreaticoduodenectomy (PD) has not been thoroughly investigated.This study aims to evaluate the clinical utility of preoperative PhA in predicting postoperative complications for patients undergoing PD. Methods: Among 41 patients who underwent PD at Seoul National University Hospital between September and December 2024, 35 were included in the analysis after excluding 6 patients who had concomitant blood vessel or other organ resections. Patients were divided into low (Comprehensive Complication Index [CCI] ≤ 20) and high (CCI > 20) complication groups based on the CCI, derived from the Clavien–Dindo classification. The differences in PhA between the two groups were analyzed, and logistic regression was performed to assess the relationship between PhA and CCI. Results: The mean PhA was significantly lower in the high-CCI group compared to the low-CCI group (5.7° vs. 6.7°, p = 0.025). Multivariate logistic regression analysis indicated that PhA (odds ratio: 0.17; 95% confidence interval: 0.04–0.68; p = 0.012) was an independent predictor of high CCI. A low preoperative PhA was associated with an increased risk of postoperative complications following PD. Conclusions Preoperative PhA may serve as a valuable predictive indicator of postoperative complications after PD, enabling the identification of patients who could benefit from preoperative prehabilitation, including nutritional support.

Gastroesophageal reflux disease (GERD) is a chronic and relapsing gastrointestinal disorder characterized by the reflux of gastric contents into the esophagus, leading to troublesome symptoms and/or complications. Since the publication of the 2020 Seoul Consensus on GERD, significant new evidence has emerged, particularly regarding acid-suppressive therapies and diagnostic approaches. This 2025 focused update aims to refine GERD management strategies by incorporating the latest evidence on acid suppressive therapies and regional considerations in Asian populations. This study builds on the 2020 Seoul Consensus by integrating systematic reviews, meta-analyses, and expert consensuses to offer updated recommendations for the definition and medical treatment of GERD. These guidelines incorporate recent advances in acid-suppressive therapies, particularly potassium-competitive acid blockers, and adopt updated diagnostic frameworks in accordance with the Lyon Consensus 2.0. Key clinical questions were identified and structured using the following format: Population, Intervention, Comparator, Outcome. The resulting recommendations address the initial treatment, long-term maintenance strategies, and role of personalized therapy based on disease severity, such as the grade of reflux esophagitis. Six key statements are presented: updated definition and classification of GERD (Statement 1); initial and long-term treatment strategies tailored to GERD phenotypes, such as non-erosive reflux disease, mild erosive esophagitis, and severe erosive esophagitis (Statements 2-5); and dose optimization strategies for long-term safety (Statement 6). These guidelines aim to support gastroenterologists and general healthcare providers in making individualized evidence-based decisions for GERD management.

The Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) is widely used for risk stratification in pheochromocytoma and paraganglioma (PPGL), but its clinical utility is limited by inter-observer variability of its parameters and inconsistent predictive performance. Methods: We conducted a multicenter retrospective study of 1,518 patients with PPGL from five tertiary referral centers in Korea. Prognostic utility of PASS system was assessed using logistic regression, Kaplan-Meier analysis, and receiver operating characteristic (ROC) curve analysis. Inter-observer variability was inferred by comparing area under the ROC curve (AUCs) across institutions. Simplified PASS systems were developed based on multivariable analysis of key histopathological parameters. Results: The PASS system was a significant predictor of adverse events and recurrence-free survival. Although the PASS system demonstrated only modest discriminative ability (AUC, 0.673), it showed a high negative predictive value (NPV, 0.885), supporting its usefulness as a screening tool for benign behavior. However, there was significant inter-institutional variability in PASS performance (AUC; range, 0.513 to 0.727; p < .05). The 3-factor Simple PASS, which incorporates necrosis, spindling, and mitotic figures, exhibited less inter-observer variation. The 4-factor Simple PASS, which adds vascular invasion to the 3-factor model, also showed reduced inter-observer variability and improved AUC and NPV compared to the original PASS system. Conclusions: In this multicenter cohort, the PASS system demonstrated high NPV and screening potential, but significant inter-observer variability remains a challenge. Simplification of the PASS system and enhanced pathologist training may improve reproducibility and clinical utility in PPGL risk stratification.

Objective: Although most gallbladder polyps are benign, some neoplastic polyps may be malignant or may serve as precursors to malignancy. Distinguishing neoplastic and non-neoplastic polyps using imaging examinations remains a major challenge.This meta-analysis aimed to identify the ultrasound (US) features that are significantly associated with neoplastic polyps. Materials and Methods: The MEDLINE, EMBASE, Cochrane, and KoreaMed databases were searched for articles published up to August 31, 2025. Bivariate random-effects models were used to calculate the meta-analytic pooled diagnostic odds ratios (DORs), sensitivities, and specificities, along with their 95% confidence intervals (CIs), for each US imaging feature in the diagnosis of neoplastic polyps. Results: Thirty studies evaluating 8,953 patients, including 1,216 (13.6%) patients with neoplastic polyps, were included.Among the nine evaluated US imaging features, namely, size ≥10 mm, sessile morphology, single polyp, coexisting gallstones, hypoechogenicity, heterogeneous echogenicity, gallbladder wall thickening (GBWT), absence of hyperechoic spot, and vascularity, eight were significantly associated with neoplastic polyps: size ≥10 mm (DOR: 6.23 [95% CI: 1.86– 20.90]), sessile morphology (DOR: 3.54 [1.93–5.97]), single polyp (DOR: 2.21 [1.76–2.74]), coexisting gallstones (DOR:1.86 [1.29–2.60]), hypoechogenicity (DOR: 3.55 [1.47–7.30]), GBWT (DOR: 9.38 [1.47–32.20]), absence of hyperechoic spots (DOR: 4.23 [2.46–6.83]), and vascularity (DOR: 9.72 [5.81–15.30]). Of these, size ≥10 mm demonstrated the highest pooled sensitivity (0.79 [95% CI: 0.68–0.87]), whereas hypoechogenicity showed the highest pooled specificity (0.93 [95% CI: 0.82–0.98]). Conclusion Eight US imaging features (size ≥10 mm, sessile morphology, single polyp, coexisting gallstones, hypoechogenicity, GBWT, absence of hyperechoic spots, and vascularity) were significantly associated with the presence of neoplastic polyps.These features may facilitate the management of gallbladder polyps.

Bowel preparation is a key determinant of colonoscopy quality; however, inadequate cleansing remains common among patients with overlapping clinical and logistical barriers. In routine practice, preparation failure may prolong procedures, reduce diagnostic confidence, and necessitate early repeat colonoscopy. We review major society guidelines and selected studies addressing bowel preparation in inflammatory bowel disease (IBD), chronic kidney disease (CKD), older adults, chronic constipation, and hospitalized patients. Across these settings, the most consistently supported measures include split-dose administration, completion of the final dose close to the time of colonoscopy in accordance with local fasting and sedation policies, and structured patient instructions reinforced through follow-up communication. A standardized assessment of preparation quality is recommended to support quality improvement and appropriate follow-up. Risk stratification can help identify patients who may benefit from intensified preparation pathways, including those with prior inadequate preparation, severe constipation, frailty, or inpatient status. Safety considerations are particularly important in CKD, in which oral sodium phosphate should be avoided and magnesium-containing agents used cautiously; polyethylene glycol-based solutions are generally preferred. In IBD, regimen selection should also consider endoscopic interpretability because sodium phosphate preparations have been associated with preparation-related mucosal abnormalities that may confound the assessment of subtle inflammatory findings. Among hospitalized patients, system-level barriers often predominate, and protocolized pathways may improve workflow and patient comfort while maintaining cleansing effectiveness. We propose a practical, risk-stratified approach to regimen selection, timing, rescue strategies, and safety monitoring that can be implemented in high-volume clinical practice.

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.

Purpose: Although human epidermal growth factor receptor 2 (HER2) positivity is prevalent in microinvasive breast cancer (MIBC), data focused on HER2-positive MIBC are limited. We investigated the clinical course and long-term outcomes of HER2-positive MIBC and evaluated the role of adjuvant chemotherapy. Materials and Methods: The study included patients with curatively resected pT1mi pN0 HER2-positive breast cancer between January 2000 and January 2020. Treatments and survival outcomes, including invasive breast cancer-free survival (IBCFS), distant recurrence-free survival (DRFS), and overall survival (OS) were analyzed. Results: The analysis included 799 female patients. The median age was 51 years (range, 23 to 79 years), and 51.6% (n=412) were premenopausal. Multifocality was confirmed in 17.3% (n=138), and estrogen receptor (ER) positivity in 29.8% (n=238). Adjuvant chemotherapy was administered to 17.5% (n=140), with doxifluridine in 96.4% of cases. One patient (0.1%) received trastuzumab. With a median follow-up of 119.0 months (95% confidence interval [CI], 114.0 to 127.0), the 8-year IBCFS, DRFS, and OS were 91.2% (95% CI, 89.1 to 93.3), 97.5% (95% CI, 96.4 to 98.7), and 98.8% (95% CI, 98.0 to 99.6), respectively. No significant differences were observed between patients with and without adjuvant chemotherapy. The lack of differences in IBCFS by chemotherapy was consistent across subgroups, including pre-/postmenopausal patients, grade 1-2/3 tumors, and ER-negative disease. Conclusion A clinically meaningful proportion of HER2-positive MIBC patients experience IBCFS events with long-term follow-up. Adjuvant chemotherapy did not improve survival, potentially due to the use of an outdated, ineffective regimen. The role of modern adjuvant regimens, particularly those incorporating HER2-targeted therapy, warrants further exploration.