Purpose: To develop and validate an artificial intelligence (AI)-based personalized outcome prediction model for upper-urinary tract urothelial carcinoma patients undergoing radical nephroureterectomy. Materials and Methods: Data from patients who underwent radical nephroureterectomy between 2010 and 2020 across three hospitals were retrospectively analyzed. A model was developed using one tertiary center’s data and externally validated with data from two other hospitals. An AI model using XGBoost as risk estimator and bootstrapped Weibull Accelerated Failure Time model for 10-year survival probability was employed. Hyperparameter tuning used Optuna method. Model efficacy was assessed using concordance index, average Brier score, D-calibration, and six-month interval time-dependent area under the curve (AUC). Results: Of 1,039 patients, 627 qualified after excluding 50 with neoadjuvant chemotherapy. Model development used 564 patients (507 training, 57 test) with 9:1 stratified random split, plus 63 for internal validation and 362 for external validation. Significant parameters included preoperative glomerular filtration rate (p<0.001), hydroureteronephrosis (p=0.013), pathological N stage (p<0.001), concurrent carcinoma in situ (p<0.001), disease progression (p<0.001), and survival rate (p<0.001). Disease-free survival (DFS) model’s concordance index: internal validation 0.789, external validations 0.734 and 0.771. Overall survival (OS) model’s concordance index: internal validation 0.819, external validations 0.780 and 0.771. Mean time-dependent AUC was 0.66–0.77 for DFS and 0.67–0.80 for OS during 10-year periods. Conclusions AI-based model effectively predicts disease-free and OS outcomes for upper-urinary tract urothelial carcinoma patients with post-radical nephroureterectomy, showcasing robust performance across multicenter settings.

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.

Enterococcus faecium, particularly in its multidrug-resistant forms, causes invasive nosocomial infections. Given the limited data comparing the effectiveness of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the CLSI clinical breakpoints (CBPs) for quinupristin–dalfopristin (QD) resistance and the need to evaluate their practical application, we retrospectively investigated the susceptibility patterns of 287 E.faecium bloodstream isolates from Korean hospitals to QD using the updated EUCAST and CLSI CBPs and two antimicrobial susceptibility testing methods: disk diffusion (DD) and Sensititre broth microdilution (Sensititre). QD resistance rates were 5.9% (CLSI) and 18.8% (EUCAST) for DD and 22.6% (CLSI) and 28.2% (EUCAST) for Sensititre. The most prevalent QD resistance gene types among QD-resistant isolates were ermB+msrC+ or ermB– msrC+. Categorical agreement between DD and Sensititre ranged from 77.7% to 90.7%, depending on the testing method and CBPs applied. The EUCAST zone diameter CBPs more effectively help identify QD-resistant E. faecium isolates using the DD method than the CLSI zone diameter CBPs. In comparison, the CLSI minimum inhibitory concentration (MIC) CBPs provide more reliable results for resistance classification in the Sensititre method than EUCAST MIC CBPs. These findings would help improve clinical decision-making for treating multidrug-resistant E. faecium infections.

Purpose: The association between the fecal microbiota and colorectal cancer (CRC) risk has been suggested in epidemiologic studies. However, data from large-scale population-based studies are lacking. Materials and Methods: In this case-control study, we recruited 283 CRC patients from the Center for Colorectal Cancer, National Cancer Center Hospital, Korea to perform 16S rRNA gene sequencing of fecal samples. A total of 283 age- and sex-matched healthy participants were selected from 890 cohort of healthy Koreans that are publicly available (PRJEB33905). The microbial dysbiosis index (MDI) was calculated based on the differentially abundant species. The association between MDI and CRC risk was observed using conditional logistic regression. Sparse Canonical Correlation Analysis was performed to integrate species data with microbial pathways obtained by PICRUSt2. Results: There is a significant divergence of the microbial composition between CRC patients and controls (permutational multivariate analysis of variance p=0.001). Those who were in third tertile of the MDI showed a significantly increased risk of CRC in the total population (odds ratio [OR], 6.93; 95% confidence interval [CI], 3.98 to 12.06; p-trend < 0.001) compared to those in the lowest tertile. Similar results were found for men (OR, 6.28; 95% CI, 3.04 to 12.98; p-trend < 0.001) and women (OR, 7.39; 95% CI, 3.10 to 17.63; p-trend < 0.001). Bacteroides coprocola and Bacteroides plebeius species and 12 metabolic pathways were interrelated in healthy controls that explain 91% covariation across samples. Conclusion Dysbiosis in the fecal microbiota may be associated with an increased risk of CRC. Due to the potentially modifiable nature of the gut microbiota, our findings may have implications for CRC prevention among Koreans.

Purpose: This multicenter, open-label, phase II trial evaluated the efficacy and safety of bortezomib combined with dexamethasone for the treatment of relapsed/refractory cutaneous T-cell lymphoma (CTCL) in previously treated patients across 14 institutions in South Korea. Materials and Methods: Between September 2017 and July 2020, 29 patients with histologically confirmed CTCL received treatment, consisting of eight 4-week cycles of induction therapy followed by maintenance therapy, contingent upon response, for up to one year. The primary endpoint was the proportion of patients achieving an objective global response. Results: Thirteen of the 29 patients (44.8%) achieved an objective global response, including two complete responses. The median progression-free survival (PFS) was 5.8 months, with responders showing a median PFS of 14.0 months. Treatment-emergent adverse events were generally mild, with a low incidence of peripheral neuropathy and hematologic toxicities. Despite the trend toward shorter PFS in patients with higher mutation burdens, genomic profiling before and after treatment showed no significant emergence of new mutations indicative of disease progression. Conclusion This study supports the use of bortezomib and dexamethasone as a viable and safe treatment option for previously treated CTCL, demonstrating substantial efficacy and manageability in adverse effects. Further research with a larger cohort is suggested to validate these findings and explore the prognostic value of mutation profiles.

Objective: Recently, various mental health promotion programs using virtual reality (VR) technology have been tried in the psychiatric field. Considering the importance of mental health in pregnant women, VR-assisted mental health promotion programs for pregnant women are needed to be developed. This study aimed to prospectively investigate the efficacy of a VR-assisted mental health promotion program for pregnant women. Methods: Fifty-five pregnant women were participated in this study. Mental health states such as depression, anxiety, perceived stress, and quality of life were assessed by Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), Perceived Stress Scale, and World Health Organization Quality of Life Scale Abbreviated Version (WHOQOL-BREF) before and after using VR program treatment. Based on the mental health types of pregnant women classified by cluster analysis, the effects of the VR program were analyzed by paired t test and Wilcoxon signed rank test. Results: The VR program significantly reduced PHQ-9 (p = 0.033) and GAD-7 (p = 0.046) scores, and significantly increased WHOQOL-BREF (p = 0.026) score of the participants. Additionally, when classifying the mental health types of pregnant women, the VR program was significantly effective to improve depression, anxiety, and quality of life in the most severe group based on the cluster analysis. Conclusion The results of this study suggest that VR program may be effective to improve the mental health of pregnant women. Particularly, VR programs for the high-risk group of depression might be the most effective. Therefore, VR-assisted mental health promotion programs could be useful for managing the mental health in pregnant women.

Background: Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making. Methods: This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes. Conclusion This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.

Recent studies have shown an increased abundance of Sphingomonas paucimobilis, an aerobic, Gram-negative bacterium with a distinctive cell envelope rich in glycosphingolipids, within the gut microbiome of individuals with Alzheimer Disease (AD). However, the fact that S. paucimobilis is a well-known pathogen associated with nosocomial infections presents a significant challenge in investigating whether its presence in the gut microbiome is detrimental or beneficial, particularly in the context of AD. This study examines the impact of S. paucimobilis-derived extracellular vesicles (Spa-EV) on Aβ-induced pathology in cellular and animal models of AD. Microarray analysis reveals that Spa-EV treatment modulates Aβ42-induced alterations in gene expression in both HT22 neuronal cells and BV2 microglia cells. Among the genes significantly affected by SpaEV, notable examples include Bdnf, Nt3/4, and Trkb, which are key players of neurotrophic signaling; Pgc1α, an upstream regulator of mitochondrial biogenesis; Mecp2 and Sirt1, epigenetic factors that regulate numerous gene expressions; and Il1β, Tnfα, and Nfκb-p65, which are associated with neuroinflammation. Remarkably, Spa-EV effectively reverses Aβ42-induced alteration in the expression of these genes through the upregulation of Mecp2. Furthermore, administration of Spa-EV in Tg-APP/PS1 mice restores the reduced expression of neurotrophic factors, Pgc1α, MeCP2, and Sirt1, while suppressing the increased expression of proinflammatory genes in the brain. Our results indicate that Spa-EV has the potential to reverse Aβ-induced dysregulation of gene expression in neuronal and microglial cells. These alterations encompass those essential for neurotrophic signaling and neuronal plasticity, mitochondrial function, and the regulation of inflammatory processes.

Background/Aims: This study aimed to evaluate the performance of the Model for End-Stage Liver Disease (MELD) 3.0 for predicting mortality and liver-related complications compared with the Child-Pugh classification, albumin-bilirubin (ALBI) grade, the MELD, and the MELD sodium (MELDNa) score. Methods: We evaluated a multicenter retrospective cohort of incorporated patients with cirrhosis between 2013 and 2019. We conducted comparisons of the area under the receiver operating characteristic curve (AUROC) of the MELD3.0 and other models for predicting 3-month mortality. Additionally, we assessed the risk of cirrhosis-related complications according to the MELD3.0 score. Results: A total of 3,314 patients were included. The mean age was 55.9±11.3 years, and 70.2% of the patients were male. Within the initial 3 months, 220 patients (6.6%) died, and the MELD3.0had the best predictive performance among the tested models, with an AUROC of 0.851, outperforming the Child-Pugh classification, ALBI grade, MELD, and MELDNa. A high MELD3.0score was associated with an increased risk of mortality. Compared with that of the group with a MELD3.0 score <10 points, the adjusted hazard ratio of the group with a score of 10–20 pointswas 2.176, and that for the group with a score of ≥20 points was 4.892. Each 1-point increase inthe MELD3.0 score increased the risk of cirrhosis-related complications by 1.033-fold. The risk of hepatorenal syndrome showed the highest increase, with an adjusted hazard ratio of 1.149, followed by hepatic encephalopathy and ascites. Conclusions The MELD3.0 demonstrated robust prognostic performance in predicting mortality in patients with cirrhosis. Moreover, the MELD3.0 score was linked to cirrhosis-related complications, particularly those involving kidney function, such as hepatorenal syndrome and ascites.

Background/Aims: The Korean guidelines for Helicobacter pylori treatment were revised in 2020, however, the extent of adherence to these guidelines in clinical practice remains unclear. Herein, we initiated a prospective, nationwide, multicenter registry study in 2021 to evaluate the current management of H.pylori infection in Korea. Methods: This interim report describes the adherence to the revised guidelines and their impact on firstline eradication rates. Data on patient demographics, diagnoses, treatments, and eradication outcomes were collected using a web-based electronic case report form. Results: A total of 7,261 patients from 66 hospitals who received first-line treatment were analyzed.The modified intention-to-treat eradication rate for first-line treatment was 81.0%, with 80.4% of the prescriptions adhering to the revised guidelines. The most commonly prescribed regimen was the 14-day clarithromycin-based triple therapy (CTT; 42.0%), followed by tailored therapy (TT; 21.2%), 7-day CTT (14.1%), and 10-day concomitant therapy (CT; 10.1%). Time-trend analysis demonstrated significant increases in guideline adherence and the use of 10-day CT and TT, along with a decrease in the use of 7-day CTT (all p<0.001). Multivariate logistic regression analysis revealed that guideline adherence was significantly associated with first-line eradication success (odds ratio, 2.03; 95% confidence interval, 1.61 to 2.56; p<0.001). Conclusions The revised guidelines for the treatment of H. pylori infection have been increasingly adopted in routine clinical practice in Korea, which may have contributed to improved first-line eradication rates. Notably, the 14-day CTT, 10-day CT, and TT regimens are emerging as the preferred first-line treatment options among Korean physicians.