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.

Levothyroxine overdose is uncommon in adults and often presents with variable clinical severity, ranging from overt thyrotoxicosis to an entirely asymptomatic course. We report the case of a 47-year-old woman with a history of total thyroidectomy who intentionally ingested 10 mg of levothyroxine along with supratherapeutic doses of zolpidem and clonazepam at once in a suicide attempt. She presented three days later without adrenergic or gastrointestinal symptoms. Laboratory tests revealed markedly elevated free thyroxine and total triiodothyronine with suppressed thyroid stimulating hormone. She was treated with propranolol for heart rate control and empirical hydrocortisone in case of adrenal insufficiency. She remained asymptomatic with gradual biochemical improvement and normalization of thyroid function on follow-up. The protective effect of co-ingested supratherapeutic doses of gamma-aminobutyric acid (GABA)-ergic agents suggests a potential role for anti-anxiety medications in mitigating severe adrenergic symptoms in endogenous thyrotoxicosis, such as Graves’ disease.

Purpose: Triple-negative breast cancer (TNBC) is a frequent phenotype of BRCA-mutanttumors. Tumors with BRCAness may show characteristics of BRCA-mutant tumors and respond to similar treatments. Next-generation sequencing is an efficient and cost-effective method for simultaneously sequencing multiple cancer susceptibility genes, surpassing conventional Sanger testing. Methods: A total of 148 women with TNBC were recruited from December 2015 to November 2018, as part of a sub-analysis based on the PEARLY trial data. Of them, 103 patients received neoadjuvant chemotherapy (NCT). The targeted genes related to hereditary cancers were sequenced using the 65-gene germline next-generation sequencing (gNGS) panel pathogenic and likely pathogenic variants (P&LPs) were determined by Sanger sequencing. We examined the occurrence of pathologic complete remission (ypCR) in patients with P&LPs. Results: The patients’ median age was 47 years (range, 27–69 years). Twenty (13.7%) of 148 patients had P&LP in six genes, including BARD1 (n = 2), BRCA1 (n = 9), BRCA2 (n = 5), CHEK2 (n = 1), RAD51C (n = 1), and RAD51D (n = 2). Among the 103 patients with NCT, 43 (41.7%) achieved ypCR (P&LPs; 9 individuals vs. non-variants; 34 individuals). Among the 103 patients with NCT, 14 (9.3%) had P&LPs. Nine of 14 patients with P&LPs, including BARD1 (n = 2), BRCA1 (n = 4), BRCA2 (n = 1), RAD51C (n = 1), and RAD51D (n = 1), achieved ypCR, showing a trend toward statistical significance (p = 0.066). Conclusion Germline P&LP mutations in TNBC patients can be detected by gNGS. This panel test can identify BRCA and BRCAness mutations that may predict ypCR in TNBC.

Neuropathic pain markedly impairs quality of life and imposes a substantial socioeconomic burden, while available treatments often provide only partial relief and are limited by safety concerns. The Neuropathic Pain Special Interest Group of the International Association for the Study of Pain (NeuPSIG-IASP) first published pharmacologic recommendations in 2007, followed by a major update in 2015 and a new guideline in 2025. This narrative review specifically compares the 2015 and 2025 NeuPSIG-IASP guidelines, outlining key methodological changes and therapeutic shifts. The 2025 guideline is based on a larger, more rigorous meta-analysis, maintains α2δ-ligands (adds mirogabalin), serotonin-noradrenaline reuptake inhibitors, and tricyclic antidepressants as first-line drugs, downgrades tramadol into the opioid third-line group. It also introduces high-frequency motor-cortex repetitive transcranial magnetic stimulation as a weakly recommended third-line option and discusses implications for Korean clinical practice.

Purpose: To investigate long-term topographic progression of the geographic atrophy (GA) area based on location and analyze its correlation with visual acuity in patient with GA secondary to non-neovascular age-related macular degeneration in South Korean patient cohort. Methods: Medical records and imaging data of 58 eyes from 34 patients with GA were retrospectively reviewed using fundus autofluorescence (FAF). Regions of interest were defined as concentric ring-shaped zones with diameters of 1, 2, 3, and 4 mm centered on the fovea (zones 0–3), each subdivided into superior, temporal, inferior, and nasal sectors. The foveal center was determined using optical coherence tomography, and sectoral GA areas were measured on FAF with the semiautomated software (RegionFinder ver. 2.6.2.0). Correlations among GA area enlargement, GA growth rate, and changes in best-corrected visual acuity (BCVA) were evaluated. Results: The mean GA area enlarged from 4.10 to 16.57 mm2 and mean BCVA decreased from 0.34 to 1.06 logMAR at 5 years of follow-up. The mean overall GA area growth rate was 1.96 mm2/yr. During yearly follow-up from baseline to 5 years, there were significant differences in GA growth rate of zone 3 inferior (p < 0.005). The GA area changes of zone 3 inferior was significantly correlated with BCVA. In the subgroup with BCVA decreased under 1.0 logMAR during follow-up, there was a higher growth rate in zone 2 nasal sector, 2 to 3 years before. Conclusions The overall GA growth rate was 1.96 mm2/yr in the 5-year follow-up of our cohort. Changes in the GA growth rate in the nasal perifoveal region (zone 2) may be associated with subsequent clinically meaningful visual decline.

Purpose: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, necessitating the identification of novel therapeutic targets. The E3 ubiquitin ligase WW domain-containing E3 ubiquitin protein ligase 2 (WWP2) has been implicated in various cancers, yet its specific role and underlying molecular mechanisms in CRC are poorly understood. This study aimed to investigate the functional role of WWP2 in CRC progression and to elucidate its regulatory mechanisms. Methods: WWP2 expression was evaluated in CRC patient tissues and cell lines using immunohistochemistry, quantitative real-time polymerase chain reaction, and western blotting. The biological functions of WWP2 were assessed using in vitro assays for cell proliferation, migration, and invasion following adenovirus-mediated overexpression. The molecular mechanism was investigated by analyzing the protein expression levels of p53 and its downstream target, p21, via western blot. An in vivo xenograft mouse model was used to confirm the oncogenic role of WWP2. Results: WWP2 expression was significantly upregulated in CRC tissues. Overexpression of WWP2 promoted CRC cell proliferation, migration, and invasion. Mechanistically, increased WWP2 expression led to a marked reduction in the protein levels of the tumor suppressor p53. Consequently, the expression of the p53 downstream target, the cell cycle inhibitor p21, was also suppressed. In the xenograft model, WWP2 overexpression significantly enhanced tumor growth. Conclusion Our findings demonstrate that WWP2 functions as an oncogene in CRC. It promotes cancer progression by destabilizing the tumor suppressor p53 and downregulating p21. This study highlights the WWP2-p53-p21 axis as a potential novel therapeutic target for CRC.

Alzheimer’s disease (AD) is characterized by progressive cognitive deterioration and significant depression. However, the mechanisms linking depression to AD pathology remain unclear. Here, we investigated whether Notch2 signaling mediates depressionlike behaviors in presenilin-2 (PS2) N141I mutant mice, an early-onset AD model. PS2 wild-type (WT) and mutant (MT) mice aged 12-15 months were subjected to unpredictable chronic mild stress (UCMS) for 4 weeks, followed by sucrose preference, tail-hanging, and forced swimming tests. Behavioral assessments showed that UCMS exacerbated anhedonia and immobility only in PS2 MT mice. Molecular analysis revealed concomitant increases in plasma corticosterone, hippocampal γ-secretase activity, and Notch2 expression, and elevated total and phosphorylated glucocorticoid receptor levels in PS2 MT-UCMS mice. Gene expression profiling of human hippocampal datasets confirmed upregulation of NOTCH2 in Alzheimer’s disease and depression.Pharmacological inhibition of γ-secretase and Notch signaling with DAPT normalizes depressive behavior, reduces corticosterone release, attenuates GR phosphorylation, and inhibits Notch2 signaling in PS2 MT mice. These findings identify Notch2 as a pivotal mediator linking chronic stress to molecular changes associated with depression and AD, and suggest that targeting Notch2 signaling may provide therapeutic benefits for comorbid mood and neurodegenerative disorders.

Purpose: The male predominance in the incidence of gastric cancer (GC) is established; however, sex differences in the prognosis of GC remain controversial. As such, this study analyzed the prognosis of patients with GC based on age and sex. Materials and Methods: Data from 14,739 patients diagnosed with GC at Seoul National University Bundang Hospital between 2003 and 2023 were analyzed. Baseline characteristics, histological types of GC, overall and GC-specific survival rates (age and stage stratification), and associated risk factors were analyzed. Results: Females were significantly younger (p < 0.001) and exhibited more gastric body cancers (p < 0.001) and tumors with diffuse-type or poorly differentiated histology (p < 0.001) than males. Females exhibited an advantage over males in terms of overall survival (p=0.004), but not in GC-specific survival. However, age stratification revealed significant sex differences, that females < 50 years of age exhibited survival disadvantages (p < 0.001); however, this trend was reversed with age, and females > 60 years exhibited survival advantages (p < 0.001) for both overall and GC-specific survival. This may be explained by the lower ratio of diffuse-type GC as females age. Furthermore, in the analysis according to stage, females with stage IV disease exhibited significant survival disadvantages, with significantly younger age and a higher proportion of diffuse-type GC which exhibits aggressive features, resulting in poorer survival than in males. Conclusion Age and stage stratification revealed significant differences in survival between the sexes, which can be helpful for public health strategies.