Squamous cell carcinomas of unknown primary (SCCUP), accounting for approximately 5
Gastric cancer (GC) remains a global health burden. While international guidelines share consensus, variations exist in disputed issues. The 2025 Taiwan Consensus and Management Guidelines for Gastric Cancer had just been released. We compared the key recommendations with established international guidelines. A multidisciplinary taskforce addressed key questions and recommendations using modified Delphi method and evidence-based approaches. The comparative review aimed to elucidate similarities and differences among guidelines from Taiwan, Japan, South Korea, China, Europe, and the US. Guidelines converge on absolute endoscopic resection criteria for early GC but differ in extended indications and perioperative approaches for locally advanced disease. Heterogeneity exists in biomarker assessment protocols, cutoff thresholds, and companion diagnostics. For metastatic disease, consensus exists on anti-HER2, anti-VEGF, immunotherapy, and biomarker-driven strategies, though oligo-metastatic definitions and intraperitoneal chemotherapy indications remain controversial. Optimal GC management requires integrating global evidence with regional contexts. The comparative review addresses heterogeneity among international guidelines, which helps harmonize management strategies as therapeutic standards evolve.
Renal progression remains a major unmet clinical challenge in patients with type 2 diabetes mellitus (T2DM). The hemoglobin glycation index (HGI), reflecting inter-individual variability in hemoglobin glycation independent of glucose levels, has been proposed as a complementary glycemic marker; however, its prognostic value for renal outcomes remains uncertain. We conducted a prospective cohort study of 441 adults with T2DM followed at a tertiary medical center between 2016 and 2021. HGI was calculated as the difference between observed HbA1c and predicted HbA1c derived from fasting plasma glucose. Baseline and mean first-year HGI and HbA1c were categorized into tertiles. Renal progression was defined as new-onset albuminuria or a ≥ 30
Cardiac toxicity from QT-prolonging drugs can precipitate malignant ventricular arrhythmias in susceptible individuals, and family screening may clarify inherited risk. We report a 33-year-old woman with a history of postpartum cardiac arrest treated with a secondary-prevention implantable cardioverter-defibrillator (ICD) who developed an electrical storm after self-administration of a single low dose of amitriptyline (12.5 mg). ICD interrogation documented 176 episodes of ventricular fibrillation requiring repeated shocks, followed by complete battery depletion, hemodynamic collapse, and the need for venoarterial extracorporeal membrane oxygenation and continuous renal replacement therapy. The admission electrocardiogram showed marked QT prolongation (QTc 651 ms), with previously documented prolonged baseline QTc values. Targeted next-generation sequencing identified a novel SCN5A missense variant (NM_000335.5:c.5738G > A) and a rare pathogenic KCNQ1 splice variant (NM_000218.3:c.1032G > C), cascade testing across the family demonstrated variable expressivity among carriers. Given a suspected contribution of late sodium current, a mechanism-based strategy was implemented with mexiletine added to propranolol and overdrive pacing (90 bpm). This case underscores the risk of malignant ventricular arrhythmias after exposure to QT-prolonging agents even at low doses, and supports genotype-informed, mechanism-based therapy to mitigate arrhythmic risk in patients with marked QT prolongation.
Epilepsy-dyskinesia syndromes (EDS) are a complex group of neurogenetic disorders characterized by the co-occurrence of epilepsy and movement disorders. Despite their increasing clinical recognition, the molecular and clinical spectrum of EDS remains poorly understood. While numerous genetic aetiologies have been implicated, systematic characterization across diverse populations is lacking. This study aimed to delineate the molecular and clinical landscape of EDS in a large, multinational cohort, focusing on movement disorder phenomenologies, genotype-phenotype correlations, and treatment responses. We conducted a multicentre, cross-sectional study involving 609 patients with childhood-onset movement disorders associated with pathogenic variants in 105 predefined genes. Clinical data were collected from over 30 centres across 25 countries using a standardized survey, capturing movement disorder phenomenologies, seizure types, developmental trajectories, motor function and treatment outcomes. We classified EDS-associated genes into biologically meaningful groups by performing unsupervised clustering, which integrated protein-protein interactions and functional data. Genotype-phenotype correlations were assessed using a one-versus-remainder approach to quantify differential enrichment of clinical manifestations and treatment responses. Pathogenic variants were identified in 74 of the 105 predefined genes, with 12 genes accounting for two-thirds of cases. The most frequently reported genes were MECP2, ATP1A3, and GNAO1. Data-driven gene cluster analysis identified 12 functional groups, mapping EDS to relevant biological pathways and informing genotype-phenotype analyses. Dystonia (34.2%), stereotypies (24.6%) and ataxia (16.2%) were the most prevalent movement disorders, with gene- and pathway-specific movement disorder signatures extending beyond previously known associations. Notably, most patients exhibited mixed movement disorders, highlighting the phenotypic complexity of EDS. Epilepsy was diagnosed in only 66.8% of cases, suggesting that some EDS primarily manifest as movement disorders. Developmental trajectories varied by genetic aetiology. Pharmacological responses demonstrated gene- and pathway-specific treatment effects, confirming established therapeutic associations (e.g. PRRT2 variants responding to carbamazepine) and identifying previously unrecognized effects, such as exacerbation of motor symptoms with levodopa/carbidopa in GNAO1 and MECP2 variants. This study provides a detailed characterization of EDS, identifying distinct genetic, phenotypic and therapeutic patterns. The findings underscore the need for early recognition of movement disorders within epilepsy cohorts, offer immediate insights to improve anticipatory guidance and clinical management of EDS, and advocate for personalized treatment strategies. By laying the groundwork for longitudinal studies to refine genotype-phenotype correlations and establish a natural history, this work paves the way for interventional clinical trials and precision medicine approaches.
