Background/Objectives: Reflux esophagitis (RE) is a chronic inflammatory disorder caused by reflux of gastric contents into the esophagus, leading to mucosal injury and epithelial barrier dysfunction. Although proton pump inhibitors are widely used, persistent inflammation and oxidative stress remain important therapeutic challenges. Yeokwisan (YWS) is prescribed for gastroesophageal reflux disease and functional dyspepsia; however, its protective mechanisms against RE remain unclear. This study investigated the protective and anti-inflammatory effects of YWS. Methods: We integrated network pharmacology analysis, mechanistic studies in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, and efficacy evaluation in a rat model of acute RE induced by pyloric and forestomach ligation. Results: Network pharmacology identified 174 common targets between YWS and RE and 23 hub genes through protein-protein interaction network and topological analyses, implicating PI3K/Akt, MAPK, Ras, HIF-1, chemokine, and other inflammation-related signaling pathways. In LPS-stimulated RAW264.7 macrophages, YWS significantly reduced intracellular reactive oxygen species, nitric oxide, TNF-α, and IL-6 production without inducing cytotoxicity and suppressed MAPK, PI3K/Akt, and NF-κB activation. In vivo, YWS attenuated acute reflux-induced esophageal mucosal injury and histopathological alterations, restored esophageal superoxide dismutase activity, reduced malondialdehyde levels, and lowered serum TNF-α, IL-6, and IL-1β levels. YWS also suppressed NF-κB/IκB activation and COX-2 expression in esophageal tissue. Conclusions: YWS exerted protective effects against acute reflux-induced esophageal injury and anti-inflammatory effects in activated macrophages, accompanied by attenuation of oxidative stress and inflammation-associated signaling. These findings support further investigation of YWS for reflux-associated esophageal inflammation.

Esophageal adenocarcinoma (AC) incidence has increased markedly in the United States and other Western countries over recent decades. Gastro-esophageal reflux disease (GERD) can cause Barrett's esophagus, which is strongly associated with the development of AC. However, the mechanisms underlying the pathogenesis of AC remain poorly elucidated. In this exploratory pilot study, we performed transcriptomic profiling by RNA sequencing (RNA-seq) on six normal esophagus (WT), four Barrett's esophagus with low-grade dysplasia (BL), and six esophageal adenocarcinoma (AC) samples using RNA extracted via laser capture microdissection (LCM) of histologically confirmed formalin-fixed paraffin-embedded (FFPE) esophageal biopsies. Differential gene expression analysis demonstrated partial separation according to histological group, with overlap between BL and AC. BL and AC groups displayed a multitude of differentially expressed genes relative to WT samples; however, fewer differentially expressed genes were found when comparing BL and AC groups. We identified 3062 differentially expressed genes across comparisons (2289 WT vs. AC; 1854 WT vs. BL; 130 BL vs. AC). Using KEGG pathway analysis and functional annotation, candidate genes and pathways were identified. Genes related to the extracellular matrix, focal adhesion, and PI3K-AKT pathways were upregulated in BL and AC versus WT, while genes relating to keratinization, Ras/Rap1, and Hippo signaling were downregulated in BL and AC versus WT. A small set of genes (e.g., ANPEP, REG4, MEP1A) distinguished BL from AC and represent differentially expressed candidates for further investigation. This exploratory transcriptomic profiling provides insights into gene expression changes associated with AC pathogenesis and identifies candidate genes and pathways that warrant independent validation by qRT-PCR, immunohistochemistry, and functional studies.

Barrett's esophagus (BE), the intestinal metaplasia arising from chronic gastroesophageal reflux disease, is the principal identifiable precursor of esophageal adenocarcinoma (EAC), whose incidence rose from 0.4 to 2.8/100,000 person-years between 1975 and 2017 and whose prognosis, once symptomatic, remains poor. Because outcomes depend on intercepting the metaplasia-dysplasia-carcinoma sequence, diagnostic accuracy is decisive. White-light endoscopy with Seattle-protocol biopsy remains the reference standard, yet it is constrained by the following three interrelated weaknesses: sampling error, as random forceps biopsies interrogate only about 3.5% of the Barrett's mucosa; poor reproducibility of dysplasia grading, with interobserver agreement of only κ 0.24-0.27 for the pivotal distinction of low-grade dysplasia; and a substantial burden of missed disease, with roughly one-quarter of EACs diagnosed within a year of an index endoscopy reported as nondysplastic. This review synthesizes the technologies converging to address these gaps. Advanced imaging, encompassing high-definition endoscopy, narrow-band imaging, acetic acid chromoendoscopy, and the optical-biopsy platforms confocal laser and volumetric laser endomicroscopy, raises dysplasia yield by approximately 34% over standard white-light examination. Image-enhanced endoscopy improves targeted detection while remaining complementary to structured biopsy sampling. Molecular, genetic, and epigenetic biomarkers, notably DNA-content abnormalities, p53 immunohistochemistry, and multi-gene methylation panels, add an objective read on progression risk. Their pairing with non-endoscopic sampling, including Cytosponge-TFF3, capsule endoscopy, exhaled volatile organic compounds, and circulating microRNA liquid biopsy, is reshaping screening at population scale, while artificial intelligence standardizes interpretation and narrows the expert-nonexpert gap. Together these advances point toward a risk-stratified, multimodal paradigm, though prospective validation and cost-effectiveness evidence remain prerequisites for guideline adoption.

Background/Objectives: Artificial intelligence (AI) is increasingly proposed for digital self-management, yet early-stage platforms may not be clinically or organizationally ready for AI-enabled functions. Most responsible-AI guidance begins after a model has been proposed and gives limited attention to whether AI should be introduced at all. This Perspective proposes a Responsible AI Readiness Framework for digital self-management platforms. Methods: The framework was developed through a targeted integrative synthesis, concept extraction, domain consolidation, and comparison with established digital-health and AI frameworks. It was applied qualitatively, without scoring, to Sokcare, a rule-based mobile platform for gastroesophageal reflux symptoms. No participant-level data were analyzed. Conceptual Findings: The framework begins with an AI necessity and proportionality screen and then examines eight readiness domains. In the Sokcare audit, 18 of 20 fixed mission statements were classified as Revise and 2 as Retain; none were classified as Remove. A non-version-linked interface design record also contained legacy symptom-improvement and personalization wording that exceeded the intended self-management claim boundary. The case otherwise showed potential foundations in interpretability, user agency, and modular architecture, alongside gaps in clinical validation, safety escalation, cybersecurity, accessibility, implementation, and lifecycle monitoring. Conclusions: The framework may support structured pre-adoption AI decisions, but its transferability and decision consistency require testing across independent platforms, clinical areas, and regulatory settings.

Complete excision of the hernial sac during congenital hiatal hernia repair may help prevent recurrence. This case also emphasizes the importance of early recognition and prompt management of abdominal compartment syndrome when progressive abdominal distension and organ dysfunction develop postoperatively.

Background/Objectives: Chimeric antigen receptor T-cell (CAR-T) therapy has been approved for the management of relapsed and refractory hematologic malignancies, transforming the oncologic landscape and producing durable remissions in patient populations with limited alternatives. The systemic adverse events of CAR-T are well characterized; however, the orofacial adverse events have not been well described. The objective of this study is to leverage a large, de-identified, real-world dataset to (1) estimate the prevalence of orofacial adverse events following CAR-T, (2) compare event rates with the general population, and (3) directly contrast the orofacial toxicity burden of CAR-T with that observed after hemopoietic stem cell transplant (HSCT). Methods: We performed a retrospective cohort study using de-identified electronic health record data from TriNetX. CAR-T and HSCT cohorts were identified via RxNorm and procedure codes; a non-exposed control cohort was included. Patients with prior orofacial conditions or confounding therapies were excluded. New adverse orofacial events within one year were identified by International Classification of Diseases, 10th Revision (ICD-10) codes. Cohorts were 1:1 propensity-matched by age and sex; associations were estimated as odds ratios with two-sided 95% CIs. Results: In 1142 CAR-T recipients (mean age of 62), gastroesophageal reflux disease (GERD) was most frequent (5.18%). Oral mucosal events included stomatitis in 1.52%, mucositis in 1.31%, and lichenoid reactions in 1.03%. Dysphagia occurred in 1.8% and oral candidiasis in 1.6%. Several severe oral conditions were absent. Compared with the general population (CART vs. general population): mucositis-[12/995 vs. 0/1112] (OR 28.3)-and stomatitis-[16/987 vs. 0/1119] (OR 38)-risks were significantly increased, while CAR-T patients had significant lower risks of mucosal complications than HSCT recipients in this analysis (CART vs. HSCT): mucositis-[1.21% vs. 3.72%] (OR 0.316) and stomatitis-[1.42% vs. 3.91%] (OR 0.354). Conclusions: CAR-T therapy carries a distinct and generally lower orofacial toxicity burden than HSCT, but targeted dental assessment and prospective surveillance remain important to optimize supportive care for cellular therapy recipients.