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.

Objective: This study investigated how educational levels modify the relationship between the standard deviation of NN intervals (SDNN) of heart rate variability and the development of post-traumatic stress disorder (PTSD). Methods: Participants with physical injuries were enrolled from a trauma center and monitored over two years. Initial assessments included SDNN and educational attainment, along with socio-demographic and clinical variables. PTSD diagnoses were made at 3, 6, 12, and 24 months post-injury using the Clinician-Administered PTSD Scale for DSM-5.Logistic regression analyses were conducted. Results: Of the 538 participants, 58 (10.8%) developed PTSD during the follow-up period. A significant interaction effect was observed: lower SDNN was significantly linked to PTSD in individuals with higher education, but not in those with lower education. Conclusion The study identified education-dependent associations between SDNN and PTSD development, emphasizing the importance of tailored PTSD prevention strategies that consider both SDNN and educational levels.

Background: The treatment of Kümmell disease (KD) is controversial. Corpectomy and reconstruction or osteotomy with long-level fusion was traditionally performed for the advanced KD. However, these procedures can be disadvantageous for elderly patients.Several alternative surgical procedures including transpedicular intravertebral cage augmentation (TPICA) or vertebroplasty (VP) combined with short-segment fixation (SSF) have been suggested to minimize the surgical burden. This study aimed to compare the outcomes of percutaneous TPICA plus SSF with VP plus SSF for advanced thoracolumbar (T11–L2) KD and to introduce our novel percutaneous TPICA technique using specially designed cannulated cage trials. Methods: We devised specially designed cannulated cage trials to make the TPICA procedure safer and more reproducible, minimizing the risk of the pedicle medial wall violation. All consecutive patients who underwent percutaneous TPICA or VP combined with SSF for advanced thoracolumbar KD, from January 2021 to June 2022, with ≥ 1-year follow-up at a single institution, were included. Perioperative details, clinical outcomes (visual analog scale and Oswestry Disability Index), and radiological outcomes (anterior vertebral body compression percentage and vertebral kyphotic angle [VKA] of the fractured vertebra, and local Cobb angle [LCA]) were collected and compared between the groups. Results: A total of 42 patients were enrolled, with 21 patients in each group. There were no patients with pedicle medial wall fracture in the TPICA group. Both procedures provided significantly favorable radiological outcomes compared to those preoperatively. No significant differences were observed in the changes over time in all radiological parameters between the groups. Loss of correction during the follow-up period was significantly smaller in patients with TPICA than in those with VP in VKA (median [interquartile range], 2.15 [0.30–2.80] vs. 2.90 [0.90–6.53]; p = 0.030) and LCA (2.70 ± 2.90 vs. 5.17 ± 4.40, p = 0.037). Conclusions Both procedures are minimally invasive and useful options for advanced KD, especially for elderly patients with high comorbidity. Our novel percutaneous TPICA technique using cannulated cage trials, being safer and more reproducible, may allow spine surgeons to easily perform TPICA.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

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.

Background: The positive relationship between triiodothyronine (T3) and steatotic liver disease (SLD) demonstrated only in crosssectional study. We aimed to evaluated whether total T3 (TT3) is associated with the development/resolution of SLD in longitudinal design. Methods: This retrospective, longitudinal, population-based cohort study included 1,665 South Korean euthyroid adults with ≥4 thyroid function test. We explored the impact of mean TT3 during follow-up on development/resolution of either SLD (diagnosed by ultrasound) or modified metabolic dysfunction-associated steatotic liver disease (MASLD) using Cox proportional hazards regression models. Results: During about median 5 years follow-up, 807/1,216 (66.3%) participants among participants without SLD at baseline developed SLD, and 253/318 (79.5%) participants among participants with SLD at baseline SLD resolved fatty liver. Mean TT3 rather than thyroid stimulating hormone or mean free thyroxine was significantly related with development (adjusted hazard ratio [HR], 1.01; 95% confidence interval [CI], 1.00 to 1.02; P=0.002) and resolution (adjusted HR, 0.97; 95% CI, 0.96 to 0.99; P=0.005) of SLD. Compared with low mean TT3 group, high mean TT3 group was positively associated with development of SLD (adjusted HR, 1.20; 95% CI, 1.05 to 1.38; P=0.008) and inversely associated with resolution of SLD (adjusted HR, 0.66; 95% CI, 0.51 to 0.85; P=0.001). The statistical significance remained for development (adjusted HR, 1.29; 95% CI, 1.10 to 1.51; P=0.001) and resolution (adjusted HR, 0.71; 95% CI, 0.54 to 0.94; P=0.018) of modified MASLD. Conclusion In Korean euthyroid adults, TT3 level was associated with development and resolution of either SLD or modified MASLD.

Background/Aims: We investigated the clinical practice patterns of Korean endoscopists for the endoscopic resection of colorectal polyps. Methods: From September to November 2021, an online survey was conducted regarding the preferred resection methods for colorectal polyps, and responses were compared with the international guidelines. Results: Among 246 respondents, those with <4 years, 4–9 years, and ≥10 years of experiencein colonoscopy practices accounted for 25.6%, 34.1%, and 40.2% of endoscopists, respectively. The most preferred resection methods for non-pedunculated lesions were cold forceps polypectomy for ≤3 mm lesions (81.7%), cold snare polypectomy for 4–5 mm (61.0%) and 6–9 mm (43.5%) lesions, hot endoscopic mucosal resection (EMR) for 10–19 mm lesions (72.0%), precut EMR for 20–25 mm lesions (22.0%), and endoscopic submucosal dissection (ESD) for ≥26 mm lesions (29.3%). Hot EMR was favored for pedunculated lesions with a head size <20 mm and stalk size <10 mm (75.6%) and for those with a head size ≥20 mm or stalk size ≥10 mm (58.5%). For suspected superficial and deep submucosal lesions measuring 10–19 mm and ≥20 mm, ESD (26.0% and 38.6%) and surgery (36.6% and 46.3%) were preferred, respectively. The adherence rate to the guidelines ranged from 11.2% to 96.9%, depending on the size, shape, and histology of the lesions. Conclusions Adherence to the guidelines for endoscopic resection techniques varied depend-ing on the characteristics of colorectal polyps. Thus, an individualized approach is required to increase adherence to the guidelines.

Background/Aims: Findings on the impact of Helicobacter pylori eradication on metabolic parameters are inconsistent. This study aimed to evaluate the effects of H. pylori eradication on metabolic parameters and body composition, including body fat mass and skeletal muscle mass. Methods: We retrospectively reviewed the data of asymptomatic patients who underwent health screenings, including bioelectrical impedance analysis, before and after H. pylori eradication between 2005 and 2021. After matching individuals based on key factors, we compared lipid profiles, metabolic parameters, and body composition between 823 patients from the eradicated group and 823 patients from the non-eradicated groups. Results: Blood pressure, erythrocyte sedimentation rate, and glycated hemoglobin values were significantly lower in the eradicated group than in the non-eradicated group. However, changes in body mass index (BMI), body fat mass, appendicular skeletal muscle mass (ASM), waist circumference, and lipid profiles were not significantly different between the two groups. In a subgroup analysis of individuals aged >45 years, blood pressure, erythrocyte sedimentation rate, and glycated hemoglobin changes were significantly lower in the eradicated group than in the noneradicated group. BMI values were significantly higher in the eradicated group than in the noneradicated group; however, no significant differences were observed between the two groups regarding changes in body weight, body fat mass, ASM, or waist circumference. Total cholesterol and low-density lipoprotein cholesterol levels were significantly lower in the eradicated group than in non-eradicated group. Conclusions H. pylori eradication significantly reduced blood pressure, glucose levels, and systemic inflammation and improved lipid profiles in patients aged >45 years. BMI, body fat mass, ASM, and waist circumference did not significantly differ between patients in the eradicated group and those in the non-eradicated group.

Background/Aims: Although the urea breath test (UBT) is widely used as a representative monitoring test after Helicobacter pylori eradication, false-negative results can occur because of the gray zone related to its cutoff value. This study aimed to compare the diagnostic performances of the rapid urease test (RUT), the RUT with sweeping method, and the UBT, and to investigate the role of the sweeping method in the gray zone of UBT values. Methods: We retrospectively reviewed 216 patients who received standard first-line H. pylori eradication treatments (n=216). All participants underwent to testing using the sweeping method and UBT on the same day. The sensitivity, specificity, and accuracy were analyzed to compare the two methods. Results: The sensitivity (0.537 vs 0.806, p=0.002) and accuracy (0.843 vs 0.870, p=0.026) of the UBT were inferior to those of the sweeping method. A total of 31 individuals tested positive for H. pylori according to the UBT, whereas 54 individuals tested positive according to the sweeping method. In the group for which the gold standard definition indicated H. pylori positivity but UBT results were negative (n=31), all individuals had a UBT value under 2.5‰. In the multivariate logistic regression model, a UBT value of 1.4‰ to 2.5‰ increased the risk of false-negative results by 6.5 times (odds ratio, 6.5; 95% confidence interval, 2.077 to 20.288; p=0.001). Conclusions After H. pylori eradication, false-negative results can occur for individuals undergoing the UBT, primarily for values below the UBT cutoff. The RUT with the sweeping method can potentially help detect H. pylori in the gray zone of the UBT, improving diagnostic accuracy.

Background/Aims: The study investigated the incidence, risk factors, and clinical outcomes of chronic antibiotic-refractory pouchitis (CARP) in Korean patients with ulcerative colitis (UC). Methods: This single-center retrospective study included patients with UC who underwent total proctocolectomy with ileal pouch-anal anastomosis at the Asan Medical Center in Korea between January 1987 and December 2022. The primary outcomes were endoscopic remission and pouch failure. The Cox’s proportional hazard model was used to identify the risk factors for CARP. Results: The clinical data of 232 patients were analyzed. The most common cause of surgery was steroid refractoriness (50.9%), followed by dysplasia/colorectal cancer (26.7%). Among 74 patients (31.9%) with chronic pouchitis (CP), 31 (13.4%) had CARP, and 43 (18.5%) had chronic antibiotic-dependent pouchitis (CADP). The most frequent endoscopic phenotype was focal inflammation of the pouch (CP, 47.3%; CARP, 35.5%; CADP, 55.8%). Patients with CARP were less likely to use concomitant probiotics than patients with CADP (29.0% vs 72.1%, p<0.01). The endoscopic remission rate of CP, CARP, and CADP was 14.9%, 9.7%, and 18.6%, respectively.The pouch failure rate associated with CP, CARP, and CADP was 13.5%, 16.1%, and 11.6%, respectively. Current smoking status (adjusted hazard ratio [aHR], 2.96; 95% confidence interval [CI], 1.27 to 6.90; p=0.01) and previous use of biologics/small molecules (aHR, 2.40; 95% CI, 1.05 to 5.53; p=0.04) were significantly associated with CARP development. Conclusions UC patients who were current smokers and previously used biologics/small molecules had a higher risk of developing CARP. Concomitant use of probiotics was less likely to be associated with CARP development.