Objective: We conducted this study to assess the efficacy and safety of taltirelin hydrate (TH) in patients with ataxia due to spinocerebellar degeneration (SCD). Methods: Patients were randomly assigned to either the taltirelin group (5 mg orally, twice daily) or the control group. The primary endpoint was the change in the Korean version of the Scale for the Assessment and Rating of Ataxia (K-SARA) score at 24 weeks. The secondary endpoints included changes in the K-SARA score at 4 and 12 weeks as well as the Clinical Global Impression Scale, the five-level version of the EuroQol five-dimensional questionnaire, the Tinetti balance test, and gait analysis at 4, 12, and 24 weeks. Results: A total of 149 patients (hereditary:nonhereditary=86:63) were enrolled. There were significant differences in the change in the K-SARA score at 24 weeks from baseline between the taltirelin group and the control group (-0.51±2.79 versus 0.36±2.62, respectively; p=0.0321). For the K-SARA items, the taltirelin group had significantly lower “Stance” and “Speech disturbance” subscores than the control group (-0.04±0.89 versus 0.23±0.79 and -0.07±0.74 versus 0.18±0.67; p=0.0270 and 0.0130, respectively). However, there were no significant differences in changes in other secondary efficacy outcome measures at 24 weeks from baseline between the two treatment arms (p>0.05). Conclusion Clinicians might consider the use of TH in the treatment of patients with ataxia due to SCD.

Purpose: This study aimed to develop a magnetic resonance imaging (MRI)–based radiomics model to predict high-risk pathologic features for lung adenocarcinoma: micropapillary and solid pattern (MPsol), spread through air space, and poorly differentiated patterns. Materials and Methods: As a prospective study, we screened clinical N0 lung cancer patients who were surgical candidates and had undergone both 18F-fluorodeoxyglucose (FDG) positron emission tomography–computed tomography (PET/CT) and chest CT from August 2018 to January 2020. We recruited patients meeting our proposed imaging criteria indicating high-risk, that is, poorer prognosis of lung adenocarcinoma, using CT and FDG PET/CT. If possible, these patients underwent an MRI examination from which we extracted 77 radiomics features from T1-contrast-enhanced and T2-weighted images. Additionally, patient demographics, maximum standardized uptake value on FDG PET/CT, and the mean apparent diffusion coefficient value on diffusion-weighted image, were considered together to build prediction models for high-risk pathologic features. Results: Among 616 patients, 72 patients met the imaging criteria for high-risk lung cancer and underwent lung MRI. The magnetic resonance (MR)–eligible group showed a higher prevalence of nodal upstaging (29.2% vs. 4.2%, p < 0.001), vascular invasion (6.5% vs. 2.1%, p=0.011), high-grade pathologic features (p < 0.001), worse 4-year disease-free survival (p < 0.001) compared with non-MR-eligible group. The prediction power for MR-based radiomics model predicting high-risk pathologic features was good, with mean area under the receiver operating curve (AUC) value measuring 0.751-0.886 in test sets. Adding clinical variables increased the predictive performance for MPsol and the poorly differentiated pattern using the 2021 grading system (AUC, 0.860 and 0.907, respectively). Conclusion Our imaging criteria can effectively screen high-risk lung cancer patients and predict high-risk pathologic features by our MR-based prediction model using radiomics.

Background/Aims: Hepatocellular carcinoma (HCC) exhibits high de novo recurrence rates post-resection. Current post-surgery recurrence prediction methods are limited, emphasizing the need for reliable biomarkers to assess recurrence risk. We aimed to develop methylation-based markers for classifying HCC patients and predicting their risk of de novo recurrence post-surgery. Methods: In this retrospective cohort study, we analyzed data from HCC patients who underwent surgical resection in Korea, excluding those with recurrence within one year post-surgery. Using the Infinium Methylation EPIC array on 140 samples in the discovery cohort, we classified patients into low- and high-risk groups based on methylation profiles. Distinctive markers were identified through random forest analysis. These markers were validated in the cancer genome atlas (n=217), Validation cohort 1 (n=63) and experimental Validation using a methylation-sensitive high-resolution melting (MS-HRM) assay in Validation cohort 1 and Validation cohort 2 (n=63). Results: The low-risk recurrence group (methylation group 1; MG1) showed a methylation average of 0.73 (95% confidence interval [CI] 0.69–0.77) with a 23.5% recurrence rate, while the high-risk group (MG2) had an average of 0.17 (95% CI 0.14–0.20) with a 44.1% recurrence rate (P<0.03). Validation confirmed the applicability of methylation markers across diverse populations, showing high accuracy in predicting the probability of HCC recurrence risk (area under the curve 96.8%). The MS-HRM assay confirmed its effectiveness in predicting de novo recurrence with 95.5% sensitivity, 89.7% specificity, and 92.2% accuracy. Conclusions Methylation markers effectively classified HCC patients by de novo recurrence risk, enhancing prediction accuracy and potentially offering personalized management strategies.

Background: and Purpose: This clinical practice guideline provides evidence-based recommendations for treatment of dementia, focusing on cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists for Alzheimer’s disease (AD) and other types of dementia. Methods: Using the Population, Intervention, Comparison, Outcomes (PICO) framework, we developed key clinical questions and conducted systematic literature reviews. A multidisciplinary panel of experts, organized by the Korean Dementia Association, evaluated randomized controlled trials and observational studies. Recommendations were graded for evidence quality and strength using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Results: Three main recommendations are presented: (1) For AD, cholinesterase inhibitors (donepezil, rivastigmine, galantamine) are strongly recommended for improving cognition and daily function based on moderate evidence; (2) Cholinesterase inhibitors are conditionally recommended for vascular dementia and Parkinson’s disease dementia, with a strong recommendation for Lewy body dementia; (3) For moderate to severe AD, NMDA receptor antagonist (memantine) is strongly recommended, demonstrating significant cognitive and functional improvements. Both drug classes showed favorable safety profiles with manageable side effects. Conclusions This guideline offers standardized, evidence-based pharmacologic recommendations for dementia management, with specific guidance on cholinesterase inhibitors and NMDA receptor antagonists. It aims to support clinical decision-making and improve patient outcomes in dementia care. Further updates will address emerging treatments, including amyloid-targeting therapies, to reflect advances in dementia management.

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.

Gastric cancer is one of the most common cancers in both Korea and worldwide. Since 2004, the Korean Practice Guidelines for Gastric Cancer have been regularly updated, with the 4th edition published in 2022. The 4th edition was the result of a collaborative work by an interdisciplinary team, including experts in gastric surgery, gastroenterology, endoscopy, medical oncology, abdominal radiology, pathology, nuclear medicine, radiation oncology, and guideline development methodology. The current guideline is the 5th version, an updated version of the 4th edition. In this guideline, 6 key questions (KQs) were updated or proposed after a collaborative review by the working group, and 7 statements were developed, or revised, or discussed based on a systematic review using the MEDLINE, Embase, Cochrane Library, and KoreaMed database. Over the past 2 years, there have been significant changes in systemic treatment, leading to major updates and revisions focused on this area.Additionally, minor modifications have been made in other sections, incorporating recent research findings. The level of evidence and grading of recommendations were categorized according to the Grading of Recommendations, Assessment, Development and Evaluation system. Key factors for recommendation included the level of evidence, benefit, harm, and clinical applicability. The working group reviewed and discussed the recommendations to reach a consensus. The structure of this guideline remains similar to the 2022 version.Earlier sections cover general considerations, such as screening, diagnosis, and staging of endoscopy, pathology, radiology, and nuclear medicine. In the latter sections, statements are provided for each KQ based on clinical evidence, with flowcharts supporting these statements through meta-analysis and references. This multidisciplinary, evidence-based gastric cancer guideline aims to support clinicians in providing optimal care for gastric cancer patients.

South Korea’s current vaccination policies leave a surveillance gap for non-National Immunization Program (NIP) vaccines. In this study, we proposed a sentinel surveillance approach for monitoring the safety of non-NIP vaccines. Vaccination data were collected retrospectively among patients hospitalized with pre-defined adverse events of special interest (AESI) by reviewing electronic medical records in five university hospitals. This approach incorporates expert assessment to determine the causal relationship. We confirmed that 16 patients had received non-NIP vaccines among 860 patients diagnosed with AESI.We concluded one case of preeclampsia was possibly related to tetanus-diphtheria-pertussis vaccination. We propose a multi-hospital-based, retrospective assessment system for predefined AESIs as an alternative to active vaccine safety monitoring method. These efforts are expected to enhance both the accuracy and timeliness of safety monitoring in South Korea.

Objective: We conducted this study to assess the efficacy and safety of taltirelin hydrate (TH) in patients with ataxia due to spinocerebellar degeneration (SCD). Methods: Patients were randomly assigned to either the taltirelin group (5 mg orally, twice daily) or the control group. The primary endpoint was the change in the Korean version of the Scale for the Assessment and Rating of Ataxia (K-SARA) score at 24 weeks. The secondary endpoints included changes in the K-SARA score at 4 and 12 weeks as well as the Clinical Global Impression Scale, the five-level version of the EuroQol five-dimensional questionnaire, the Tinetti balance test, and gait analysis at 4, 12, and 24 weeks. Results: A total of 149 patients (hereditary:nonhereditary=86:63) were enrolled. There were significant differences in the change in the K-SARA score at 24 weeks from baseline between the taltirelin group and the control group (-0.51±2.79 versus 0.36±2.62, respectively; p=0.0321). For the K-SARA items, the taltirelin group had significantly lower “Stance” and “Speech disturbance” subscores than the control group (-0.04±0.89 versus 0.23±0.79 and -0.07±0.74 versus 0.18±0.67; p=0.0270 and 0.0130, respectively). However, there were no significant differences in changes in other secondary efficacy outcome measures at 24 weeks from baseline between the two treatment arms (p>0.05). Conclusion Clinicians might consider the use of TH in the treatment of patients with ataxia due to SCD.

Background: and Purpose Previous research on patients with acute ischemic stroke (AIS) has shown a 0.5% incidence of major gastrointestinal bleeding (GIB) requiring blood transfusion during hospitalization. The existing literature has insufficiently explored the long-term incidence in this population despite the decremental impact of GIB on stroke outcomes. Methods: We analyzed the data from a cohort of patients with AIS admitted to 14 hospitals as part of a nationwide multicenter prospective stroke registry between 2011 and 2013. These patients were followed up for up to 6 years. The occurrence of major GIB events, defined as GIB necessitating at least two units of blood transfusion, was tracked using the National Health Insurance Service claims data. Results: Among 10,818 patients with AIS (male, 59%; mean age, 68±13 years), 947 (8.8%) experienced 1,224 episodes of major GIB over a median follow-up duration of 3.1 years. Remarkably, 20% of 947 patients experienced multiple episodes of major GIB. The incidence peaked in the first month after AIS, reaching 19.2 per 100 person-years, and gradually decreased to approximately one-sixth of this rate by the 2nd year with subsequent stabilization. Multivariable analysis identified the following predictors of major GIB: anemia, estimated glomerular filtration rate <60 mL/min/1.73 m2 , and a 3-month modified Rankin Scale score of ≥4. Conclusion Patients with AIS are susceptible to major GIB, particularly in the first month after the onset of AIS, with the risk decreasing thereafter. Implementing preventive strategies may be important, especially for patients with anemia and impaired renal function at stroke onset and those with a disabling stroke.

Background and Objectives: Several real-world studies have been done in patients with nonvalvular atrial fibrillation (NVAF); however, information on its safety profile in patients with renal impairment is limited. XARENAL, a real-world study, aimed to prospectively investigate the safety profile of rivaroxaban in patients with NVAF with renal impairment (creatinine clearance [CrCl], 15–49 mL/min). Methods: XARENAL is an observational single-arm cohort study in renal impairment NVAF patients. Patients were followed up approximately every 3 months for 1 year or until 30 days following early discontinuation. The primary endpoint was major bleeding events. All adverse events, symptomatic thromboembolic events, treatment duration, and renal function change from baseline were the secondary endpoints. Results: XARENAL included 888 patients from 29 study sites. Overall, 713 (80.3%) had moderate renal impairment (CrCl, 30–49 mL/min), and 175 (19.7%) had severe renal impairment (CrCl, 15–29 mL/min) with a mean estimated glomerular filtration rate (eGFR) of 45.2±13.0 mL/min/1.73 m 2 . The mean risk scores were 3.3±1.4 and 1.7±0.9 for CHA 2 DS 2 -VASc score and HAS-BLED score, respectively. An incidence proportion of 5.6% (6.2 events per 100 patient-years) developed major bleeding; however, fatal bleeding occurred in 0.5% (0.5 events per 100 patient-years). The mean change in the eGFR was 2.22±26.47 mL/min/1.73 m 2 per year. Conclusions XARENAL observed no meaningful differences in major bleeding events from other previous findings as well as renal function changes in rivaroxaban-treated NVAF patients with renal impairment, which is considered to be acceptable in clinical practice.