OBJECTIVES: This study examined whether individuals with consistently normal liver enzyme levels are protected from alcohol-related liver disease and investigated whether heavy drinking increases liver disease risk independent of normal biomarker status. METHODS: We conducted a nationwide cohort study using Korean National Health Insurance Service data (2002–2019), including 19,035 participants aged ≥40 years who maintained normal liver enzyme levels (aspartate aminotransferase ≤40 μ/L, alanine aminotransferase ≤40 μ/L, gamma-glutamyl transferase ≤63 μ/L for men and ≤35 μ/L for women) across multiple examinations conducted between 2002 and 2008. Participants were categorized as abstainers (≤1 time/mo), moderate drinkers (≤2 times/wk), and heavy drinkers (≥3 times/wk). Primary outcomes included incident liver disease identified using diagnostic codes. Cox proportional hazards models were used to estimate hazard ratios (HRs), with age-stratified analyses performed. RESULTS: Heavy drinkers demonstrated a significantly higher risk of liver disease than abstainers (HR, 1.73; 95% confidence interval [CI], 1.40 to 2.14), whereas moderate drinkers showed no significant association (HR, 1.06; 95% CI, 0.94 to 1.19). Consistent patterns emerged for middle-aged adults (40–69 years), with attenuated effects among participants aged ≥70 years. When alcoholic liver disease was analyzed specifically, both moderate (HR, 1.29; 95% CI, 1.05 to 1.58) and heavy drinkers (HR, 2.86; 95% CI, 2.09 to 3.91) exhibited significantly increased hazards. CONCLUSIONS Despite normal liver enzyme levels, heavy alcohol consumption was associated with a significantly increased risk of liver disease. These findings challenge current reactive screening paradigms relying solely on biomarker abnormalities and support proactive alcohol counseling regardless of enzyme results. More sensitive strategies are needed for early detection of alcohol-related liver injury.

Mitochondrial bioenergetics plays a fundamental role in neuronal development and function. Prenatal exposure to corticosterone in rats (Corti.Pup) has previously been shown to cause delayed neurodevelopment and synaptic plasticity deficits, showing attention deficit hyperactivity disorder (ADHD) - like behaviors. However, the underlying mitochondrial metabolic adaptations remain unclear. This study investigated mitochondrial function and metabolic remodeling in prefrontal cortex neurons of Corti.Pups, focusing on oxidative phosphorylation, calcium handling, and redox balance. We assessed neuronal viability, reactive oxygen species (ROS) production, and oxygen consumption rate (OCR) through experiments conducted in both neuron-glia co-culture and neuron-only conditions. Furthermore, we evaluated electron transport chain (ETC) activity, mitochondrial membrane potential (MMP), and mitochondrial Ca2+ uptake in purified isolated mitochondria. In results, Corti.Pup neurons exhibited increased vulnerability to glutamate-induced excitotoxicity in the absence of glial support. Despite reduced ROS production, these neurons showed elevated mitochondrial OCR and proton leak, coupled with decreased non-mitochondrial OCR and ETC complex activity. Surprisingly, MMP remained elevated despite ETC dysfunction, and mitochondrial Ca2+ uptake was suppressed. These features indicate mitochondrial metabolic reprogramming, prioritizing MMP maintenance over ATP synthesis. The observed mitochondrial inefficiency and compensatory adaptations may impair energy production, contributing to delayed neuronal development in Corti.Pups. These findings suggest that mitochondrial dysfunction and metabolic remodeling play central roles in the pathogenesis of neurodevelopmental disorders such as ADHD.

In patients with differentiated thyroid cancer (DTC), initial recurrence risk stratification based on clinical, histopathological, and perioperative data remains the key determinant for guiding management strategies during the first 1-2 years post-treatment. However, the adoption of ongoing risk stratification (ORS), which dynamically reassesses risk by integrating longitudinal clinical data and treatment response, enables more precise long-term prognostic assessment and facilitates highly individualized management. Building upon recent guidelines, the 2026 KTA guideline has been further refined by incorporating robust evidence from large-scale national cohorts and comprehensive systematic reviews. These updated recommendations outline contemporary concepts of ORS, risk-adapted TSH suppression targets, optimized surveillance modalities for recurrence detection, and disease-specific long-term follow-up strategies. Reflecting the paradigm shift toward de-escalated treatment, this revision integrates evolved perspectives on TSH suppression intensity, the clinical interpretation of thyroglobulin levels, and tailored follow-up intervals. These evidence-based recommendations aim to minimize unnecessary treatment and excessive surveillance in the large proportion of patients with excellent prognosis after initial therapy, while ensuring that each patient receives appropriately tailored and effective long-term management.

Background and Objectives: Studies investigating the correlation between papillary thyroid carcinoma (PTC) tumor size and the prevalence of the B-type Raf kinase (BRAF) mutation have yielded conflicting results. Therefore, we evaluated the prevalence of BRAF mutation according to tumor size in a large cohort of PTC patients to clarify this association. Materials and Methods: We retrospectively analyzed 6,438 patients with surgically diagnosed classic PTC between January 2009 and December 2017 at Samsung Medical Center, Seoul, Republic of Korea.During the study period, BRAF mutation testing was attempted on all fine-needle aspiration specimens, except for a small number of inadequate specimens. All other histologic subtypes were excluded. The prevalence of BRAF mutation was assessed based on tumor size, and further analyzed by age group and sex according to tumor size. Results: The overall prevalence of BRAF mutation was 79.2%. When PTCs ≤1 cm were excluded, the prevalence was 77.2%. The prevalence significantly decreased with increasing tumor size (p for trend ＜0.001). It was significantly higher in men than in women (p=0.013), but did not differ by age. The inverse correlation between tumor size and prevalence was prominent in patients aged 20-49 years but was less distinct in those aged 50 years and older. Conclusion In this large cohort of patients with PTC, the prevalence of BRAF mutation significantly decreased with increasing tumor size. These findings suggest that BRAF mutation is enriched in smaller surgically treated classic PTCs and may provide a hypothesis-generating clue regarding its role in early PTC development, although selection bias cannot be excluded.

Purpose: Lobular carcinoma In Situ (LCIS) is a noninvasive lesion associated with an increased risk of invasive cancer. Since its removal from the tumor, node, metastasis classification in the 8th edition of the American Joint Committee on Cancer (AJCC) guidelines, the clinical management of LCIS has shifted from surgery to surveillance. However, studies focusing on the risk and associated factors for invasive cancer development in pure LCIS without ductal carcinoma In Situ (DCIS) or invasive cancer remain limited. Methods: We retrospectively analyzed 106 patients diagnosed with pure LCIS between 2008 and 2018. This study evaluated the effect of tamoxifen use and histologic type on the development of invasive cancer. Results: All 106 patients underwent surgery, and nine (8.5%) developed invasive cancer over a median follow-up of 67.5 months. The incidence of invasive cancer was lower in the tamoxifen group (6.3%, n = 4) than in the non-tamoxifen group (11.9%, n = 5), although this difference was not statistically significant (p = 0.266). Pleomorphic LCIS had a significantly higher incidence of invasive cancer (30.0%, n = 3) than classic LCIS (6.3%, n = 6) (p = 0.045).Multivariable Cox regression analysis showed no significant difference in the risk of invasive cancer according to tamoxifen use (hazard ratio [HR], 2.031; 95% confidence interval [CI], 0.544–7.579; p = 0.292). However, pleomorphic LCIS showed a trend toward an increased risk of invasive cancer compared to classic LCIS (HR, 3.856; 95% CI, 0.922–16.126; p = 0.064). Conclusion Postoperative tamoxifen did not significantly lower invasive cancer development in patients with pure LCIS. Pleomorphic LCIS may carry a higher risk than classic LCIS. These findings require tailored follow-up and treatment strategies based on the histologic subtype of LCIS.

Background: There are limited long-term clinical outcome data comparing first-generation (1G) versus second-generation (2G) drug-eluting stents (DES) in patients with single-vessel disease (SVD). We sought to compare the efficacy and safety of 1G- and 2G-DES in SVD patients who underwent successful percutaneous coronary intervention (PCI) over 10 years of clinical follow-up. Methods: A total of 2,312 consecutive patients with SVD who underwent PCI with 1G-DES (paclitaxel- or sirolimus-eluting stents, n = 811) or 2G-DES (zotarolimus [Endeavor, Endeavor Resolute]- or everolimus-eluting stents [Promus Element, Xience], n = 1,082) were enrolled.After propensity score matching, 2 matched groups (538 pairs) were generated. Study endpoints included individual and composite clinical outcomes through 10 years. Results: During the 10-year follow-up, the 2G-DES group had lower incidences of myocardial infarction (MI; hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.22–0.92; P = 0.028) and target lesion revascularization (TLR; HR, 0.54; 95% CI, 0.32–0.91; P = 0.021) than the 1G-DES group. Rates of total death, cardiac death, non-target vessel revascularization, stroke, major adverse cardiac events, and major adverse cardiac and cerebrovascular events were similar between groups. Conclusions In our single-center, all-comer registry, 2G-DES were associated with lower incidence rates of MI and TLR compared to 1G-DES in SVD patients over 10 years of followup, indicating a safer and more durable effect than 1G-DES.

Hepatocellular carcinoma (HCC) is a highly invasive tumor with a strong tendency for metastasis. The most common sites of metastasis are the lungs, followed by lymph nodes, adrenal glands, and bones. However, metastasis of HCC to the small bowel is extremely rare. A 42-yearold female with HCC secondary to chronic hepatitis B and lung metastasis underwent a right hepatic lobectomy, followed by two wedge resections performed via video-assisted thoracic surgery, four sessions of transcatheter arterial chemoembolization, and stereotactic body radiation therapy. She was under regular follow-up for HCC, during which her alpha-fetoprotein level increased to 722.2 IU/ml. Abdominal computed tomography (CT) revealed segmental wall thickening and aneurysmal dilatation of the small bowel loops. An 18 F-fluorodeoxyglucose positron emission tomography/CT scan demonstrated a 3.3-cm hypermetabolic mass-like lesion (standardized uptake value: 11.3) in the small bowel. Surgical resection of the affected small bowel segment was performed. Histopathological examination of the specimen confirmed metastatic HCC, with immunohistochemical positivity for hepatocyte-specific antigen. The patient has remained cancer-free for 60 months post-operatively. Surgical intervention may offer favorable long-term outcomes in patients with small bowel metastasis from HCC.

Purpose: This study evaluated the clinical outcomes and prognostic factors in patients with borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC) treated with upfront FOLFIRINOX followed by local-regional therapy (LRT), surgical resection (SR), and radiotherapy (RT). We aimed to identify specific patient subgroups for which RT may serve as a reasonable alternative to SR for local tumor control. Methods: We retrospectively analyzed 116 patients (SR group, n= 70; RT group, n= 46) at a single center between 2015 and 2020. Survival outcomes were compared based on LRT modalities, focusing on identifying subgroups in which RT provided an efficacy comparable to that of SR. Results: Among 116 patients, the SR group achieved a significantly higher 5-year overall survival (OS) than the RT group (27.1% vs. 8.7%, P< 0.0001), despite similar progression-free survival (P= 0.23). Significant prognostic factors for OS included carbohydrate antigen 19-9 (CA19-9) response in BRPC (P= 0.02) and radiologic partial response in LAPC (P= 0.05). Subgroup analysis revealed that, while SR provided a survival advantage in CA19-9 responders, no significant difference in OS was observed between SR and RT in CA19-9 non-responders (P= 0.37). Conclusion Although surgery remains the gold standard, RT may be considered a justifiable local alternative for CA19-9 non-responders and surgically ineligible patients with LAPC, yielding comparable outcomes in these specific, biologically unfavorable subgroups.

Objectives: Tegoprazan is an alternative to proton pump inhibitors (PPIs). This study evaluated the occurrence of upper gastrointestinal (GI) and cardiovascular (CV) complications in patients with ischemic heart disease undergoing antiplatelet therapy after percutaneous coronary intervention (PCI) who were treated with tegoprazan or PPIs. Methods: Data from 604 patients who received antiplatelet therapy with tegoprazan or PPIs for >6 months after PCI between March 2019 and November 2023 were retrospectively analyzed. The primary GI endpoints were symptomatic gastroduodenal ulcers and upper GI bleeding, while the primary CV endpoints comprised major adverse cardiac events (MACEs), nonfatal myocardial infarction (MI), target vessel revascularization, and death from CV-related causes. Results: Among the 604 patients, 265 received tegoprazan and 339 received PPIs. During a mean follow-up of 17 months, seven patients experienced a GI event (0.4% with tegoprazan vs. 1.8% with PPIs; p=0.112) and 12 experienced MACEs (1.1% with tegoprazan vs. 2.7% with PPIs; p=0.183). Subgroup analysis indicated that target vessel revascularization occurred in six patients, with event rates of 0.8% (n=2) for tegoprazan and 1.2% (n=4) for PPIs (p=0.598). Tegoprazan was associated with similar rates of nonfatal MI (0.8% vs. 2.4%; p=0.125) and death from CV-related causes (0.4% vs. 0%; p=0.258) as PPIs. Conclusions There were no significant differences in GI- or CV-related complications between patients treated with tegoprazan and those treated with PPIs.

Background: To investigate Korean neurologists' perceptions of the non-standard term ‘jayulsingyeongsiljo’ and their actual evaluation and management of such patients. Methods: We performed an anonymous web-based cross-sectional survey of board-certified Korean neurologists by Korean Society of Pain and Autonomic Disorders between August 13 and September 10, 2025. A questionnaire sent by e-mail asked about demographics, experience with patients labeled with ‘jayulsingyeongsiljo,’ use and perceived usefulness of autonomic function tests, the impact of coronavirus disease 2019, and opinions on terminology and the role of neurologists. Results: In total, 109 neurologists responded. Most reported that patients presenting for ‘jayulsingyeongsiljo’ were young or middle-aged adults and that their numbers had increased over the preceding 2 years. Referrals frequently originated from Korean medicine clinics and other non-neurology departments, often after stand-alone heart rate variability testing. Fatigue, orthostatic intolerance, palpitations, sweating abnormalities, gastrointestinal symptoms, and anxiety or insomnia were common, and autonomic testing was generally regarded as helpful. Eighty percent felt that the risks associated with ‘jayulsingyeongsiljo’ are overstated, and 95% preferred replacing the term with standardized expressions such as autonomic dysfunction. Conclusions Korean neurologists view ‘jayulsingyeongsiljo’ as an unrecognized and potentially misleading label and support society-led standardization of terminology and guidance to improve autonomic dysfunction care and resource use.