Purpose: This study investigated the changes in gene expression in retinal ganglion cells (RGCs) following ciliary neurotrophic factor (CNTF) treatment to elucidate the underlying mechanisms contributing to its neuroprotective effects. Methods: RGCs isolated from Sprague-Dawley rat pups were treated with recombinant CNTF. Gene expression was analyzed via microarray. Differentially expressed genes (DEGs) were defined as those with a fold change greater than 2 or less than –2. The DEGs were further explored using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Results: Our analysis identified 71 upregulated and 58 downregulated genes. A2m exhibited the highest increase, with a fold change of 4.97, whereas Rho displayed the most significant decrease in expression, with a fold change of –6.38. GO and KEGG pathway analyses revealed substantial involvement in sensory organ development and the phototransduction pathway. Conclusions This study provides new insights into the impact of CNTF on gene expression in RGCs, suggesting broader neuroprotective mechanisms that could inform future therapeutic strategies for retinal degenerative diseases. Our findings emphasize the importance of further investigation into the complex gene network responses to CNTF treatment.

Background/Aims: Studies on the clinical outcomes after detecting low-grade dysplasia (LGD) in patients with inflammatory bowel disease (IBD) are insufficient. This study evaluated the clinical features, frequency, and risk factors for advanced neoplasia in patients with IBD after an LGD diagnosis. Methods: The medical records of 166 patients with IBD from six university hospitals in Korea from 2010 to 2019 were reviewed retrospectively. LGD was diagnosed in all patients during surveillance. The frequency and risk factors for advanced neoplasia were evaluated, and the clinical features of patients with and without advanced neoplasia were compared. Results: Advanced neoplasia developed in 12 patients (six with large LGD, three with tubulovillous adenoma, and three with high-grade dysplasia), and all cases developed from UC. Patients with advanced neoplasia had significantly higher Mayo scores, and colitis-associated dysplasia was more common than sporadic lesions (83.3% vs. 29.9%; p<0.001). Multivariate analysis showed that colitis-associated LGD significantly increased the risk of developing advanced neoplasia (odds ratio [OR], 10.516; 95% confidence interval [CI], 2.064–53.577). Among patients with colitis-associated lesions, a significant risk factor for advanced neoplasia was a prior history of LGD (OR, 9.429; 95% CI, 1.330–66.863). Conclusions Advanced neoplasia developed in 7.2% of patients with IBD and LGD. Most advanced neoplasms developed from colitis-associated lesions, and the risk was higher in patients with a history of LGD before index colonoscopy.

Background/Aims: Elevated troponin levels predict in-hospital mortality and influence decisions regarding thrombolytic therapy in patients with acute pulmonary embolism (PE). However, the usefulness of high-sensitivity troponin T (hsTnT) regarding PE remains uncertain. We aimed to establish the optimal cut-off level and compare its performance for precise risk stratification. Methods: 374 patients diagnosed with acute PE were reviewed. PE-related adverse outcomes, a composite of PE-related deaths, cardiopulmonary resuscitation incidents, systolic blood pressure < 90 mmHg, and all-cause mortality within 30 days were evaluated. The optimal hsTnT cut-off for all-cause mortality, and the net reclassification index (NRI) was used to assess the incremental value in risk stratification. Results: Among 343 normotensive patients, 17 (5.0%) experienced all-cause mortality, while 40 (10.7%) had PE-related adverse outcomes. An optimal hsTnT cut-off value of 60 ng/L for all-cause mortality (AUC 0.74, 95% CI 0.61–0.85, p < 0.001) was identified, which was significantly associated with PE-related adverse outcomes (OR 4.07, 95% CI 2.06–8.06, p < 0.001). Patients with hsTnT ≥ 60 ng/L were older, hypotensive, had higher creatinine levels, and right ventricular dysfunction signs. Combining hsTnT ≥ 60 ng/L with simplified pulmonary embolism severity index ≥1 provided additional prognostic information. Reclassification analysis showed a significant shift in risk categories, with an NRI of 1.016 ± 0.201 (p < 0.001). Conclusions We refined troponin’s predictive value in patients with acute PE, proposing a new cut-off value of hsTnT ≥ 60 ng/L. Validation through large-scale studies is essential to offer clinically useful guidance for managing patient population.

The role of acetylated apurinic/apyrimidinic endonuclease 1/redox factor 1 (APE1/Ref-1) in ovarian cancer remains poorly understood. Therefore, this study aimed to investigate the combined effect of recombinant human APE1/Ref-1 (rhAPE1/Ref-1) and aspirin (ASA) on two ovarian cancer cells, PEO-14, and CAOV3.The viability and apoptosis of ovarian cancer cells treated with rhAPE1/Ref-1 or ASA were assessed. Our results demonstrated that ASA induced rhAPE1/Ref-1 acetylation and widespread hyperacetylation in PEO-14 cells. Additionally, co-treatment with rhAPE1/Ref-1 and ASA substantially reduced cell viability and induced PEO-14 cell apoptosis, not CAOV3, in a dose-dependent manner. ASA increased the expression and membrane localization of the receptor for advanced glycation endproducts (RAGEs). Acetylated APE1/Ref-1 showed enhanced binding to RAGEs. In contrast, RAGE knockdown reduced cell death and poly(ADP-ribose) polymerase cleavage caused by rhAPE1/Ref-1 and ASA combination treatment, highlighting the importance of the APE1/Ref-1-RAGE interaction in triggering apoptosis. Moreover, combination treatment with rhAPE1/Ref-1 and ASA effectively induced apoptosis in 3D spheroid cultures of PEO-14 cells, a model that better mimics the tumor microenvironment. These results demonstrate that acetylated APE1/Ref-1 and its interaction with RAGE is a potential therapeutic target for ovarian cancer. Thus, the combination of ASA and APE1/Ref-1 may offer a promising new strategy for inducing cancer cell death.

Background and Objectives: Outcomes of deferring percutaneous coronary intervention (PCI) without invasive physiologic assessment for intermediate coronary lesions is uncertain.We sought to compare long-term outcomes between medical treatment and PCI of intermediate lesions without invasive physiologic assessment. Methods: A total of 899 patients with intermediate coronary lesions between 50% and 70% diameter-stenosis were randomized to the conservative group (n=449) or the aggressive group (n=450). For intermediate lesions, PCI was performed in the aggressive group, but was deferred in the conservative group. The primary endpoint was major adverse cardiac events (MACE, a composite of all-cause death, myocardial infarction [MI], or ischemia-driven any revascularization) at 3 years. Results: The number of treated lesions per patient was 0.8±0.9 in the conservative group and 1.7±0.9 in the aggressive group (p=0.001). At 3 years, the conservative group had a significantly higher incidence of MACE than the aggressive group (13.8% vs. 9.3%; hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.00–2.21; p=0.049), mainly driven by revascularization of target intermediate lesion (6.5% vs. 1.1%; HR, 5.69; 95% CI, 2.20–14.73;p<0.001). Between 1 and 3 years after the index procedure, compared to the aggressive group, the conservative group had significantly higher incidence of cardiac death or MI (3.2% vs.0.7%; HR, 4.34; 95% CI, 1.24–15.22; p=0.022) and ischemia-driven any revascularization. Conclusions For intermediate lesions, medical therapy alone, guided only by angiography, was associated with a higher risk of MACE at 3 years compared with performing PCI, mainly due to increased revascularization.

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: The Korean guidelines for Helicobacter pylori treatment were revised in 2020, however, the extent of adherence to these guidelines in clinical practice remains unclear. Herein, we initiated a prospective, nationwide, multicenter registry study in 2021 to evaluate the current management of H.pylori infection in Korea. Methods: This interim report describes the adherence to the revised guidelines and their impact on firstline eradication rates. Data on patient demographics, diagnoses, treatments, and eradication outcomes were collected using a web-based electronic case report form. Results: A total of 7,261 patients from 66 hospitals who received first-line treatment were analyzed.The modified intention-to-treat eradication rate for first-line treatment was 81.0%, with 80.4% of the prescriptions adhering to the revised guidelines. The most commonly prescribed regimen was the 14-day clarithromycin-based triple therapy (CTT; 42.0%), followed by tailored therapy (TT; 21.2%), 7-day CTT (14.1%), and 10-day concomitant therapy (CT; 10.1%). Time-trend analysis demonstrated significant increases in guideline adherence and the use of 10-day CT and TT, along with a decrease in the use of 7-day CTT (all p<0.001). Multivariate logistic regression analysis revealed that guideline adherence was significantly associated with first-line eradication success (odds ratio, 2.03; 95% confidence interval, 1.61 to 2.56; p<0.001). Conclusions The revised guidelines for the treatment of H. pylori infection have been increasingly adopted in routine clinical practice in Korea, which may have contributed to improved first-line eradication rates. Notably, the 14-day CTT, 10-day CT, and TT regimens are emerging as the preferred first-line treatment options among Korean physicians.

Purpose: Thrombosis and bleeding significantly affect morbidity and mortality in myeloproliferative neoplasms (MPNs). The efficacy and safety of direct oral anticoagulants (DOACs) in MPN patients remain uncertain. Materials and Methods: We conducted a large, retrospective, nationwide cohort study using the Korean Health Insurance Review and Assessment Service database from 2010 to 2021. Results: Out of the 368 MPN patients included in the final analysis, 62.8% were treated with DOACs for atrial fibrillation (AF), and 37.2% for venous thromboembolism (VTE). The AF group was statistically older with higher CHA2DS2-VASc (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke, transient ischemic attack, or thromboembolism, vascular disease, age 65-74 years, sex category [female]) scores compared to the VTE group. Antiplatelet agents were used in 51.1% of cases, and cytoreductive drugs in 79.3%, with hydroxyurea being the most common (64.9%). The median follow-up was 22.3 months, with 1-year cumulative incidence rates of thrombosis and bleeding at 11.1% and 3.7%, respectively. Multivariate analysis identified CHA2DS2-VASc scores ≥ 3 (hazard ratio [HR], 3.48), concomitant antiplatelet use (HR, 2.57), and cytoreduction (HR, 2.20) as significant thrombosis risk factors but found no significant predictors for major bleeding. Conclusion Despite the limitations of retrospective data, DOAC treatment in MPN patients seems effective and has an acceptable bleeding risk.