Background: Despite diabetes mellitus (DM) and pancreatitis being known risk factors for pancreatic cancer, patients with these conditions are not included in pancreatic cancer screening due to the low incidence of pancreatic cancer in these populations. This study aimed to determine the high-risk subgroup of patients with diabetes and pancreatitis that would benefit from pancreatic cancer screening. Methods: A nested case-control study was conducted using data from the National Health Information Database of the Korean National Health Insurance Service. Patients were categorized into the following groups: type 2 diabetes mellitus only (T2DM-only), pancreatitis-only (PAN-only), T2DM followed by pancreatitis (T2DM-PAN), post-pancreatitis diabetes mellitus (PPDM), and no diabetes and no pancreatitis (NDNP). Conditional logistic regression was used to determine significant associations of each group with pancreatic cancer development risk. Results: The risk of pancreatic cancer was significantly higher in the T2DM-PAN (adjusted odds ratio [AOR], 4.96; 95% confidence interval [CI], 4.48 to 5.49) and PPDM (AOR, 4.71; 95% CI, 4.12 to 5.37) groups than in the NDNP group. Compared to patients in the NDNP group, those with PPDM using insulin had a 17-fold increased risk (AOR, 16.72; 95% CI, 9.50 to 29.43), and individuals with PPDM who had diabetes for less than 3 years had a more than 8-fold increased risk of pancreatic cancer (AOR, 8.83; 95% CI, 5.99 to 13.01). Conclusion In patients with post-pancreatitis diabetes, insulin use or shorter duration of diabetes was associated with a higher risk of pancreatic cancer, suggesting that patients in these subgroups may require close monitoring for pancreatic cancer development.

Background: Insulin resistance (IR) is central to metabolic disorders and significantly influenced by diet. Studies on meal frequency (MF) and metabolic indicators have shown mixed results. This study explores the link between MF and IR in middle-aged and older adults. Methods: This prospective cohort study included 4,570 adults aged 40 to 69 years from the Korean Genome and Epidemiologic Study. MF were divided into two groups based on whether they consumed three or more, or fewer than three, meals daily. IR was evaluated using the homeostasis model assessment of insulin resistance (HOMA-IR); participants were classified as IR if their HOMA-IR value was ≥2.5. Multiple Cox proportional hazard regression analyses were conducted to examine the association between MF and the incidence of IR. Results: After adjusting for all variables, individuals in the MF ≥3 group showed a reduced incidence of IR compared to those in the MF <3 group (hazard ratio, 0.880; 95% confidence interval, 0.782 to 0.990). Additionally, subgroup analyses by sex, diabetes mellitus (DM), and body mass index (BMI) showed that this association persisted only in men, individuals without DM, and those with a BMI <25. Conclusion Our findings indicate that a higher MF among middle-aged and older adults is associated with a reduced incidence of IR. However, this association was maintained only in men, individuals without DM, and those without obesity.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as blockbuster drugs for treating metabolic diseases. Glucagon-like peptide-1 (GLP-1) plays a pivotal role in glucose homeostasis by enhancing insulin secretion, suppressing glucagon release, delaying gastric emptying, and acting on the central nervous system to regulate satiation and satiety. This review summarizes the discovery of GLP-1 and the development of GLP-1RAs, with a particular focus on their central mechanisms of action. Human neuroimaging studies demonstrate that GLP-1RAs influence brain activity during food cognition, supporting a role in pre-ingestive satiation. Animal studies on hypothalamic feed-forward regulation of hunger suggest that cognitive hypothalamic mechanisms may also contribute to satiation control. We highlight the brain mechanisms of GLP-1RA-induced satiation and satiety, including cognitive impacts, with an emphasis on animal studies of hypothalamic glucagon-like peptide-1 receptor (GLP-1R) and GLP-1R-expressing neurons. Actions in non-hypothalamic regions are also discussed. Additionally, we review emerging combination drugs and oral GLP-1RA formulations aimed at improving efficacy and patient adherence. In conclusion, the dorsomedial hypothalamus (DMH)—a key GLP-1RA target—mediates pre-ingestive cognitive satiation, while other hypothalamic GLP-1R neurons regulate diverse aspects of feeding behavior, offering potential therapeutic targets for obesity treatment.

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.

OBJECTIVES: The American Heart Association (AHA) recently defined cardiovascular-kidney-metabolic (CKM) syndrome to better characterize the associations among cardiovascular, kidney, and metabolic diseases. Although about 9 in 10 United States adults have at least 1 risk factor for CKM syndrome, its prevalence in other populations is less understood. To fill this gap, we examined the prevalence of CKM syndrome in Korea and its association with demographic and socioeconomic status (SES). METHODS: Using data from the Korean National Health and Nutrition Examination Survey between 2011 and 2021, we calculated the prevalence of CKM syndrome across the following stages: stage 0 (no risk factors), stage 1 (excess or dysfunctional adiposity), stage 2 (other metabolic risk factors or chronic kidney disease), and stages 3-4 (subclinical/clinical cardiovascular diseases) among adults aged ≥20 years. Weighted analyses were used to estimate prevalence and 95% confidence intervals (CIs) for each CKM syndrome stage, stratified by age, gender, and SES factors. RESULTS: Among 54,994 Korean adults, the prevalence of CKM syndrome was as follows: stage 0 (25.2%; 95% CI, 24.7 to 25.8), stage 1 (19.3%; 95% CI, 18.9 to 19.7), stage 2 (51.6%; 95% CI, 51.1 to 52.2), and stages 3-4 (3.9%; 95% CI, 3.7 to 4.0). The prevalence of stages 2 and 3-4 was higher in men than in women. In addition, stages 3-4 were more prevalent among rural residents and those with lower education or income. CONCLUSIONS About 3 out of 4 Koreans are at risk for CKM syndrome. These findings highlight that CKM syndrome is a global health problem and that interventions are urgently needed to prevent further progression.

Alzheimer disease (AD) diagnosis is confirmed using a medley of modalities, such as the detection of amyloid-β (Aβ) neuritic plaques and neurofibrillary tangles with positron electron tomography (PET) or the appraisal of irregularities in cognitive function with examinations. Although these methods have been efficient in confirming AD pathology, the rising demand for earlier intervention during pathogenesis has led researchers to explore the diagnostic potential of fluid biomarkers in cerebrospinal fluid (CSF) and plasma. Since CSF sample collection is invasive and limited in quantity, biomarker detection in plasma has become more attractive and modern advancements in technology has permitted more efficient and accurate analysis of plasma biomolecules. In this study, we found that a composite of standard factors, Aβ40 and total tau levels in plasma, divided by the variation factor, plasma Aβ42 level, provide better correlation with amyloid neuroimaging and neuropsychological test results than a level comparison between total tau and Aβ42 in plasma. We collected EDTA-treated blood plasma samples of 53 subjects, of randomly selected 27 AD patients and 26 normal cognition (NC) individuals, who received amyloid-PET scans for plaque quantification, and measured plasma levels of Aβ40, Aβ42, and total tau with digital enzyme-linked immunosorbent assay (ELISA) in a blinded manner. There was difficulty distinguishing AD patients from controls when analyzing biomarkers independently. However, significant differentiation was observed between the two groups when comparing individual ratios of total-tau×Aβ40/Aβ42. Our results indicate that collectively comparing fluctuations of these fluid biomarkers could aid in monitoring AD pathogenesis.

Background/Aims: Early colorectal cancer (ECC) is commonly resected endoscopically. Perforation is a devastating complication of endoscopic resection. We aimed to identify the characteristics and predictive risk factors for perforation related to endoscopic resection of ECC. Methods: This nationwide retrospective multicenter study included patients with ECC who underwent endoscopic resection. We investigated the demographics, endoscopic findings at the time of treatment, and histopathological characteristics of the resected specimens. Logistic regression analysis was used to investigate the clinical factors associated with procedure-related perforations. Survival analysis was conducted to assess the impact of perforation on the overall survival of patients with ECC. Results: This study included 965 participants with a mean age of 63.4 years. The most common endoscopic treatment was conventional endoscopic mucosal resection (n=573, 59.4%), followed by conventional endoscopic submucosal dissection (n=259, 26.8%). Thirty-three patients (3.4%) experienced perforations, most of which were managed endoscopically (n=23/33, 69.7%). Patients who undergo endoscopic submucosal dissection-hybrid and precut endoscopic mucosal resection have a higher risk of perforation than those who undergo conventional endoscopic mucosal resection (odds ratio, 78.65 and 39.72, p<0.05). Procedure-related perforations were not associated with patient survival. Conclusions Perforation after endoscopic resection had no significant impact on the prognosis of ECC. The type of endoscopic resection was a crucial predictor of perforation. Large-scale prospective studies are needed to further investigate endoscopic resection of ECC.

Background/Aims: Small bowel capsule endoscopy (SBCE) has become the standard for initial evaluation in the diagnosis of small bowel lesions. Although optimal visualization of the mucosa is important, patients experience difficulty in consuming a large volume of bowel preparation agents. This study aimed to compare the efficacy and safety of 1-L polyethylene glycol (PEG) with ascorbic acid (AA) and 2-L PEG with AA. Methods: In this prospective, multicenter, non-inferiority study, patients who received SBCE were randomly assigned to consume 1-L PEG with AA or 2-L PEG with AA for small bowel preparation. The primary outcome was adequate small bowel visibility quality (SBVQ). The secondary outcomes included diagnostic yield, cecal complete rate, and adverse events. Results: One hundred and forty patients were enrolled in this study, 70 patients per group. In the per-protocol analysis, there were no significant differences in the adequate SBVQ rate (94.0% vs 94.3%; risk difference, –0.3; 95% confidence interval, –8.1 to 7.6; p=1.000), diagnostic yield rate (49.3% vs 48.6%, p=0.936), or cecal complete rate (88.1% vs 92.9%, p=0.338) between the 1-L PEG with AA group and 2-L PEG with AA group. The incidence of adverse events did not differ significantly between the groups (12.9% vs 11.9%, p=0.871). Conclusions One liter-PEG with AA is not inferior to 2-L PEG with AA in terms of adequate SBVQ for SBCE. One liter-PEG with AA can be recommended as the standard method for bowel cleansing for SBCE.

Background/Aims: The aim of this study was to investigate the effect of a surgical treatment algorithm recently proposed by the American Association for the Study of Liver Diseases (AASLD) on survival outcomes in patients with early-stage hepatocellular carcinoma (HCC) and identify effective alternative treatment modalities when liver transplantation (LT) is not available. Methods: We studied the clinical data of 1,442 patients who were diagnosed with early-stage HCC (a single lesion measuring 2–5 cm in size or 2 to 3 lesions measuring ≤3 cm in size) be-tween 2013 and 2018 and classified as Child-Turcotte-Pugh (CTP) A or B. Analyses were separately performed for individuals recommended for resection (single lesion, CTP A and no clinically significant portal hypertension) and those recommended for LT (single lesion with impaired liver function such as CTP B or clinically significant portal hypertension or multiple lesions). Results: Of 791 patients recommended for surgical resection, 85.8% underwent resection. The 5-year survival rate was higher for patients who underwent surgical resection than for those who received other treatments (89.4% vs 72.3%). Among 651 patients recommended for LT, only 3.4% underwent the procedure. The most common alternative treatment modalities were transarterial therapy (39.3%) followed by resection (28.9%) and ablation (27.8%). The overall survival rate associated with transarterial therapy was lower than that for resection and ablation, whereas that of the latter two treatments were comparable. Conclusions The survival outcomes of treatment strategies that most closely aligned with the algorithm proposed by the AASLD were superior to those of alternative treatment approaches.However, LT in patients with early-stage HCC can be challenging. When LT is not feasible, resection and ablation can be considered first-line alternative options.