Purpose: This developmental study explored the conceptual feasibility and applicability of a metaverse-based clinical assessment platform as a complementary tool to conventional objective structured clinical examinations in undergraduate medical education. Methods: A targeted literature review and expert consensus process were conducted to identify domains of clinical competence in which metaverse technologies could provide added value. Based on these findings, prototype virtual patient simulations were developed within a metaverse environment. Large language models (LLMs) were integrated to support dynamic, interactive history-taking simulations, and pilot modules for physical examination were also created. Results: Integration of LLMs into virtual patient scenarios enabled realistic, context-sensitive medical interviews, facilitating interactive dialogue between examinees and simulated patients. In contrast, physical examination modules faced technical limitations, particularly in replicating procedures requiring tactile or haptic feedback, such as palpation and percussion. Nevertheless, the metaverse environment enabled delivery of consistent and reproducible scenarios, supporting objective assessment of communication and diagnostic reasoning skills. Conclusion Metaverse-based simulations augmented by LLMs offer a promising approach to scalable and standardized clinical assessment, particularly within cognitive and interpersonal competency domains. Although current technological constraints limit the fidelity of physical examination simulations, rapid advancements in immersive and haptic technologies may help overcome these barriers in the near future. Further research is needed to evaluate the educational efficacy, validity, and feasibility of deploying such platforms in summative, high-stakes assessment contexts.

Objective: To evaluate the diagnostic performance of the “probable hepatocellular carcinoma (HCC)” category in the Korean Liver Cancer Association-National Cancer Center (KLCA-NCC) v2022 guidelines. Materials and Methods: This multicenter retrospective study included patients at risk of HCC who underwent gadoxetic acid-enhanced MRI between January 2015 and June 2018; a subgroup of these patients also underwent liver CT. Eligible patients had at least one non-cystic lesion (≥10 mm) with a reference standard. Four radiologists interpreted the images independently and the results were pooled. The performance of “definite HCC” and “probable HCC” together and “probable HCC” alone were compared between v2018 and v2022. Results: A total of 2,237 patients (1,666 men; mean age, 59 ± 11 years) with 2,445 lesions were included. In v2022, 1.5% (143/9,780) of the lesions were additionally categorized as “probable HCC” by four reviewers on MRI; among these, 104 lesions were not HCCs. Focal nodular hyperplasia (FNH) or FNH-like nodules constituted 90.4% (94/104) of the false positives. When “definite HCC” and “probable HCC” were combined, v2022 showed higher sensitivity (83.7% [5,670/6,776] vs. 83.1% [5,631/6,776]) but lower specificity (77.1% [2,316/3,004] vs. 80.6% [2,420/3,004]) than v2018 (P < 0.001). For “probable HCC” alone, v2022 showed a lower positive predictive value (PPV) than v2018 (64.1% [373/582] vs. 76.1% [334/439], P < 0.001). In v2022, lesions with non-rim arterial-phase hyperenhancement (APHE) showed a lower PPV than those without APHE (42.3% [91/215] vs. 76.8% [282/367], P < 0.001). In the CT subgroup (n = 1,590), 1.6% (99/6,360) of the lesions were reassessed as “probable HCC,” and its PPV was 83.8% (83/99) in v2022 whereas no lesions were classified as “probable HCC” under v2018. Conclusion The revised “probable HCC” category in the KLCA-NCC v2022 aligns with updates in the diagnostic flow, demonstrating acceptable performance on MRI and CT. Notably, FNH or FNH-like nodules can be misclassified as “probable HCC” when MRI is used.

Purpose: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, necessitating the identification of novel therapeutic targets. The E3 ubiquitin ligase WW domain-containing E3 ubiquitin protein ligase 2 (WWP2) has been implicated in various cancers, yet its specific role and underlying molecular mechanisms in CRC are poorly understood. This study aimed to investigate the functional role of WWP2 in CRC progression and to elucidate its regulatory mechanisms. Methods: WWP2 expression was evaluated in CRC patient tissues and cell lines using immunohistochemistry, quantitative real-time polymerase chain reaction, and western blotting. The biological functions of WWP2 were assessed using in vitro assays for cell proliferation, migration, and invasion following adenovirus-mediated overexpression. The molecular mechanism was investigated by analyzing the protein expression levels of p53 and its downstream target, p21, via western blot. An in vivo xenograft mouse model was used to confirm the oncogenic role of WWP2. Results: WWP2 expression was significantly upregulated in CRC tissues. Overexpression of WWP2 promoted CRC cell proliferation, migration, and invasion. Mechanistically, increased WWP2 expression led to a marked reduction in the protein levels of the tumor suppressor p53. Consequently, the expression of the p53 downstream target, the cell cycle inhibitor p21, was also suppressed. In the xenograft model, WWP2 overexpression significantly enhanced tumor growth. Conclusion Our findings demonstrate that WWP2 functions as an oncogene in CRC. It promotes cancer progression by destabilizing the tumor suppressor p53 and downregulating p21. This study highlights the WWP2-p53-p21 axis as a potential novel therapeutic target for CRC.

Limited data exist regarding the real-world practices and clinical outcomes in patients with ischemic heart failure with reduced left ventricular ejection fractions (LVEFs).Using nationwide registry data from South Korea, we aimed to investigate long-term outcomes and clinical practices, especially implantable cardioverter defibrillators (ICDs) implantation, in patients with reduced LVEFs at least 40 days after acute myocardial infarction (AMI). Of 13,056 patients with AMI between 2011 and 2015, we analyzed 350 (median age, 66 years [interquartile range, 56-75]) who had LVEFs <40% on follow-up transthoracic echocardiogram 40 days after the index event. The primary outcome was cardiac-cause mortality at 3 years. Secondary outcomes comprised major cardiovascular events as well as outcomes defined by the use of ICDs, cardiac resynchronization therapy defibrillators (CRT-Ds), and electrophysiology studies. Among 350 patients, 39 (11.1%) died from cardiac causes during 3 years of follow-up. Eleven (3.1%) were hospitalized for ventricular tachycardia. The rate of ICD or CRT-D implantation up to 3 years was 5.7% (20/350). Cox time-to-event analysis revealed older age, LVEF <30%, diabetes mellitus, and previous MI or revascularization as positively associated with cardiac death, whereas the use of statins and body weight <67 kg were negatively associated. This nationwide Korean registry demonstrated that only 5.7% of patients who had reduced LVEFs after 40 days of AMI underwent ICD implantations over 3 years. Considering the high mortality, concerted efforts are needed to improve clinical outcomes for patients who may have been candidates for ICD implantation.

Purpose: To evaluate the clinical characteristics, etiologies, and treatment outcomes of pediatric macular holes (MHs). Methods: The medical records of pediatric patients under 18 years of age diagnosed with MHs at Severance Hospital between January 2005 and December 2022 were retrospectively reviewed. Data regarding etiology, MH diameter, treatment methods, and both visual and anatomical outcomes were analyzed. Results: Among 15 patients (16 eyes), traumatic MHs were identified in 7 cases (46.7%), while non-traumatic causes included Stargardt disease, familial exudative vitreoretinopathy, and vitreomacular traction. No statistically significant differences were observed between the traumatic and non-traumatic groups in terms of age, MH diameter, or initial and final best-corrected visual acuity (BCVA). However, there was a significant difference in sex distribution, with all traumatic cases occurring in males, whereas only 3 of the 9 non-traumatic eyes were male (p = 0.01). Surgical intervention was performed in 13 eyes, achieving anatomical closure in 62.5% (10 eyes). The three eyes without closure (37.5%) were all non-traumatic cases. BCVA (logMAR) significantly improved from a median of 1.00 preoperatively to 0.70 postoperatively (p = 0.013). Among the three eyes that did not undergo surgery, one demonstrated spontaneous closure, and another achieved closure following medical treatment. Conclusions Pediatric MHs may arise from various ocular conditions beyond trauma. Surgical intervention was effective, particularly for traumatic MHs, while non-traumatic cases demonstrated a lower closure rate. In some instances, spontaneous or medically induced closure occurred without surgical management. Further multicenter studies with larger cohorts are warranted to establish definitive management guidelines for pediatric MHs.

Background: Primary cutaneous CD30+ lymphoproliferative disorders (pcCD30-LPDs) are a diseases with various clinical and prognostic characteristics. Objective: Increasing our knowledge of the clinical characteristics of pcCD30-LPDs and identifying potential prognostic variables in an Asian population. Methods: Clinicopathological features and survival data of pcCD30-LPD cases obtained from 22 hospitals in South Korea were examined. Results: A total of 413 cases of pcCD30-LPDs (lymphomatoid papulosis [LYP], n=237; primary cutaneous anaplastic large cell lymphoma [C-ALCL], n=176) were included. Ninety percent of LYP patients and roughly 50% of C-ALCL patients presented with multiple skin lesions. Both LYP and C-ALCL affected the lower limbs most frequently. Multiplicity and advanced T stage of LYP lesions were associated with a chronic course longer than 6 months. Clinical morphology with patch lesions and elevated serum lactate dehydrogenase were significantly associated with LPDs during follow-up in LYP patients. Extracutaneous involvement of C-ALCL occurred in 13.2% of patients. Lesions larger than 5 cm and increased serum lactate dehydrogenase were associated with a poor prognosis in C-ALCL. The survival of patients with C-ALCL was unaffected by the anatomical locations of skin lesions or other pathological factors. Conclusion The multiplicity or size of skin lesions was associated with a chronic course of LYP and survival among patients with C-ALCL.

Background: Chromosomal alterations serve as diagnostic and prognostic markers in acute leukemia. Given the evolving landscape of chromosomal abnormalities in acute leukemia, we previously studied these over two periods. In this study, we investigated the frequency of these abnormalities and clinical trends in acute leukemia in Korea across three time periods. Methods: We retrospectively analyzed data from 1,787 patients with acute leukemia (319 children and 1,468 adults) diagnosed between 2006 and 2020. Conventional cytogenetics, FISH, and multiplex quantitative PCR were used for analysis. The patient groups were divided according to the following three study periods: 2006–2009 (I), 2010–2015 (II), and 2016–2020 (III). Results: Chromosomal aberrations were detected in 92% of patients. The PML::RARA translocation was the most frequent. Over the 15-yr period, chromosomal aberrations showed minimal changes, with specific fusion transcripts being common among patients.ALL was more prevalent in children than in adults and correlated significantly with the ETV6::RUNX1 and RUNX1::RUNX1T1 aberrations. The incidence of ALL increased during the three periods, with PML::RARA remaining common. Conclusions The frequency of chromosomal abnormalities in acute leukemia has changed subtly over time. Notably, the age of onset of adult AML has continuously increased. Our results may help in establishing diagnoses and clinical treatment strategies and developing various molecular diagnostic platforms.

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.

Background and Objectives: Cigarette smoking is a major risk factor for atherosclerosis.Nicotine, a crucial constituent of tobacco, contributes to atherosclerosis development and progression. However, evidence of the association between nicotine and neointima formation is limited. We aimed to evaluate whether nicotine enhances neointimal hyperplasia in the native epicardial coronary arteries of pigs after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). Methods: After coronary angiography (CAG) and quantitative coronary angiography (QCA), we implanted 20 DES into 20 pigs allocated to 2 groups: no-nicotine (n=10) and nicotine (n=10) groups. Post-PCI CAG and QCA were performed immediately. Follow-up CAG, QCA, optical coherence tomography (OCT), and histopathological analyses were performed 2 months post-PCI. Results: Despite intergroup similarities in the baseline QCA findings, OCT analysis showed that the nicotine group had a smaller mean stent and lumen areas, a larger mean neointimal area, greater percent area stenosis, and higher peri-strut fibrin and inflammation scores than the no-nicotine group. In immunofluorescence analysis, the nicotine group displayed higher expression of CD68 and α-smooth muscle actin but lower CD31 expression than the no-nicotine group. Conclusions Nicotine inhibited re-endothelialization and promoted inflammation and NIH after PCI with DES in a porcine model.

Background and Objectives: Evidence remains limited on the real-world prescription of very low-dose oral anticoagulation among frail patients with atrial fibrillation (AF). We described the practice patterns, effectiveness, and safety of very low-dose edoxaban (15 mg once daily). Methods: Patients with AF prescribed edoxaban 15 mg once daily in 2 tertiary hospitals between 2016 and September 2022 were included. Baseline clinical characteristics and clinical outcomes of interest were thromboembolic and bleeding events. Results: A total of 674 patients were included (mean age 78.3±9.1, 49.7% aged ≥80 years, 49.3% women, median follow-up 1.0±1.2 years). Mean CHA 2 DS 2 -VASc score was 3.9±1.6, and the modified HAS-BLED score was 2.0±1.1. Between 2016 and 2022, the number of very lowdose edoxaban prescriptions increased. The main reasons for the prescription of very lowdose were low body weight (55.5% below 60 kg), anaemia (62.8%), chronic kidney disease (40.2%), active cancer (15.3%), concomitant anti-platelet use (26.7%), and prior major bleeding (19.7%). During a median follow-up duration of 8 (interquartile range 3–16) months, overall thromboembolic and bleeding events occurred in 16 (2.3%) and 88 (13.1%) patients, respectively. Compared to the expected event rates on the established risk scoring systems, patients receiving very low-dose edoxaban demonstrated a 61% reduction in ischemic stroke, a 68% reduction of ischemic stroke/transient ischemic attack/systemic embolism, whereas a 49% increase in major bleeding. Conclusions The prescription of very low-dose edoxaban was increased over time, attributable to various clinical factors. The use of very low-dose edoxaban reduced the expected risk of thromboembolic events.