This study examined the inhibitory effects of pluviatolide, a lignan derived from Podophyllum hexandrum, on mast cell activation and IgE-mediated type I hypersensitivity, focusing on FcεRI-dependent and calcium-mediated pathways. Using bone marrowderived mast cells (BMMCs) and rat basophilic leukemia (RBL)-2H3 cells, we found that pluviatolide significantly decreased β-hexosaminidase release and suppressed the expression and secretion of TNF-α and IL-6 in a concentration-dependent manner, without causing cytotoxicity. While we initially hypothesized that it would selectively modulate antigen-specific FcεRI signaling, pluviatolide also inhibited degranulation induced by calcium ionophore and thapsigargin, indicating its effects extend to receptorindependent, Ca2+-dependent activation mechanisms. Immunoblot analyses revealed decreased phosphorylation of proximal kinases (Lyn, Syk), adaptor proteins (LAT, PLCγ1), MAPKs (ERK1/2, JNK, p38), and NF-κB p65. In a passive cutaneous anaphylaxis (PCA) mouse model, oral administration of pluviatolide significantly reduced Evans blue extravasation and mast cell degranulation in ear tissues. These findings demonstrate that pluviatolide suppresses both early and late-phase mast cell responses through multi-nodal inhibition of activation pathways, highlighting its potential as a therapeutic candidate for both IgE-mediated and non-IgE-mediated allergic disorders.

Janus kinase (JAK) inhibitors are an important treatment option for ulcerative colitis, providing rapid onset of action, oral administration, and efficacy even after biologic failure. The 3 approved agents—tofacitinib, filgotinib, and upadacitinib—differ in JAK isoform selectivity, leading to clinically meaningful differences in efficacy and safety. Evidence from network meta-analyses, clinical trials, and real-world studies consistently shows that upadacitinib provides the highest efficacy for induction and maintenance of remission, whereas filgotinib demonstrates the most favorable safety profile. The strong efficacy of upadacitinib and tofacitinib is particularly relevant in patients with severe disease, including acute severe ulcerative colitis, and upadacitinib maintains high efficacy regardless of prior advanced therapy exposure. JAK inhibitors also benefit extraintestinal manifestations. Although risks such as herpes zoster, serious infection, thromboembolism, and major cardiovascular events differ among agents, long-term data suggest generally acceptable safety when used appropriately. Intraclass JAK-to-JAK cycling is feasible, with about half of patients achieving steroid-free clinical remission in retrospective cohorts. Based on mechanistic, clinical, and real-world evidence, filgotinib may be a first-line option for patients with lower disease activity or when safety is a priority, whereas upadacitinib or tofacitinib may be preferred in higher disease activity. Strategically selecting agents may improve durability and outcomes.

BACKGROUND: Data on drug-coated balloon (DCB) treatment in elderly patients are limited. This study was to evaluate the efficacy of DCB treatment in percutaneous coronary intervention (PCI) among elderly patients. METHODS: A retrospective analysis included 232 patients aged 75 years or older with coronary artery disease who underwent successful PCI using either DCB alone or in combination with drug-eluting stent (DES) based on pre-dilation results (DCB-based PCI). These patients were compared with 1818 elderly patients who underwent second-generation DES implantation (DES-only PCI). The endpoint was major adverse cardiovascular events (MACE) at 2-year follow-up. RESULTS: In the DCB-based PCI, 61.2% of patients received DCB-only treatment. Compared to DES-only PCI, the DCB-based PCI group had fewer stents (0.5 ± 0.7 and 1.7 ± 0.8, P < 0.001), shorter stent lengths (13.3 ± 20.9 mm and 37.4 ± 23.0 mm, P < 0.001), and lower usage of small stents with a diameter of 2.5 mm or less (15.6% and 28.7%, P = 0.010). The DCB-based PCI group exhibited lower rate of MACE (5.5% and 13.1%, P = 0.003), target vessel revascularization (1.1% and 5.6%, P = 0.017) and major bleeding (0.7% and 5.1%, P = 0.009) at 2-year follow-up. The reduced risk in 2-year MACE was consistently observed across various matching procedures, with the most significant reduction noted in target vessel revascularization and major bleeding. CONCLUSION The DCB-based PCI reduced stent burden, particularly in the usage of small diameter stents, and was associated with lower risks of MACE, target vessel revascularization, and major bleeding compared to DES-only PCI in elderly patients.

Background/Aims: The genetic expression in the active inflammatory regions is increased in ulcerative colitis (UC) with endoscopic activity. The aim of this study was to investigate the molecular activity of inflammation and tissue remodeling markers in endoscopically inflamed and uninflamed regions of UC. Methods: Patients with UC (n=47) and controls (n=20) were prospectively enrolled at the Seoul National University Bundang Hospital. Inflamed tissue was obtained at the most active lesion, and uninflamed tissue was collected from approximately 15 cm above the upper end of the active lesion via colonoscopic biopsies. The messenger RNA expression levels of transforming growth factor β (TGF-β), interleukin (IL)-1β, IL-6, IL-17A, E-cadherin, olfactomedin-4 (OLFM4), leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), vimentin, fibroblast-specific protein-1 (FSP1), and α-smooth muscle actin (SMA) were evaluated. Mucosal healing (MH) was defined according to a Mayo endoscopic score of 0, 1 or non-MH (Mayo endoscopic score of 2 or 3). Results: The messenger RNA expressions of TGF-β, IL-1β, OLFM4, FSP1, vimentin, and α-SMA were significantly higher, and that of E-cadherin was significantly lower in inflamed and uninflamed regions of patients with UC than those in controls. In the inflamed regions, patients in the non-MH group had significantly increased genetic expression of TGF-β, FSP1, vimentin, and α-SMA compared to patients in the MH group. Similarly, the non-MH group had significantly higher genetic expression of TGF-β, IL-1β, IL-6, vimentin, and α-SMA than the MH group in the uninflamed regions. Conclusions Endoscopic activity in UC suggests inflammation and tissue remodeling of uninflamed regions similar to inflamed regions.

Background: The treatment success rate for tuberculosis (TB) has stagnated at 80–81% in South Korea, indicating unsatisfactory outcomes. Enhancing treatment success rate necessitates the development of individualized treatment approaches for each patient. This study aimed to identify the risk factors associated with unfavorable treatment outcomes to facilitate tailored TB care. Methods: We retrospectively analyzed the data of patients with active TB between January 2019 and December 2020 at a single tertiary referral center. We classified unfavorable treatment outcomes according to the 2021 World Health Organization guidelines as follows:“lost to follow-up” (LTFU), “not evaluated” (NE), “death,” and “treatment failure” (TF).Moreover, we analyzed risk factors for each unfavorable outcome using Cox proportional hazard regression analysis. Results: A total of 659 patients (median age 62 years; male 54.3%) were included in the study.The total unfavorable outcomes were 28.1%: 4.6% LTFU, 9.6% NE, 9.1% deaths, and 4.9% TF. Multivariate analysis showed that a culture-confirmed diagnosis of TB was associated with a lower risk of LTFU (adjusted hazard ratio [aHR], 0.25; 95% confidence interval [CI], 0.10–0.63), whereas the occurrence of adverse drug reactions (ADRs) significantly increased the risk of LTFU (aHR, 6.63; 95% CI, 2.63–16.69). Patients living far from the hospital (aHR, 4.47; 95% CI, 2.50–7.97) and those with chronic kidney disease (aHR, 3.21; 95% CI, 1.33–7.75) were at higher risk of being transferred out to other health institutions (NE). Higher mortality was associated with older age (aHR, 1.06; 95% CI, 1.04–1.09) and comorbidities. The ADRs that occurred during TB treatment were a risk factor for TF (aHR, 6.88; 95% CI, 2.24–21.13). Conclusion Unfavorable outcomes of patients with TB were substantial at a tertiary referral center, and the risk factors for each unfavorable outcome varied. To improve treatment outcomes, close monitoring and the provision of tailored care for patients with TB are necessary.

Background: Over the last decade, extracorporeal membrane oxygenation (ECMO) use in critically ill children has increased and is associated with favorable outcomes. Our study aims to evaluate the current status of pediatric ECMO in Korea, with a specific focus on its volume and changes in survival rates based on diagnostic indications. Methods: This multicenter study retrospectively analyzed the indications and outcomes of pediatric ECMO over 10 years in patients at 14 hospitals in Korea from January 2012 to December 2021. Four diagnostic categories (neonatal respiratory, pediatric respiratory, postcardiotomy, and cardiac-medical) and trends were compared between periods 1 (2012–2016) and 2 (2017–2021). Results: Overall, 1065 ECMO runs were performed on 1032 patients, with the annual number of cases remaining unchanged over the 10 years. ECMO was most frequently used for post-cardiotomy (42.4%), cardiac-medical (31.8%), pediatric respiratory (17.5%), and neonatal respiratory (8.2%) cases. A 3.7% increase and 6.1% decrease in pediatric respiratory and post-cardiotomy cases, respectively, were noted between periods 1 and 2.Among the four groups, the cardiac-medical group had the highest survival rate (51.2%), followed by the pediatric respiratory (46.4%), post-cardiotomy (36.5%), and neonatal respiratory (29.4%) groups. A consistent improvement was noted in patient survival over the 10 years, with a significant increase between the two periods from 38.2% to 47.1% (P = 0.004). Improvement in survival was evident in post-cardiotomy cases (30–45%, P = 0.002).Significant associations with mortality were observed in neonates, patients requiring dialysis, and those treated with extracorporeal cardiopulmonary resuscitation (P < 0.001). In pediatric respiratory ECMO, immunocompromised patients also showed a significant correlation with mortality (P < 0.001). Conclusion Pediatric ECMO demonstrated a steady increase in overall survival in Korea;however, further efforts are needed since the outcomes remain suboptimal compared with global outcomes.

Background: Coronary artery disease patients undergoing percutaneous coronary intervention (PCI) often exhibit reduced left ventricular ejection fraction (LVEF). However, the impact of LV dysfunction status in conjunction with platelet reactivity on clinical outcomes has not been previously investigated. Methods: From the multicenter PTRG-DES (Platelet function and genoType-Related long-term prognosis in DES-treated patients) consortium, the patients were classified as preserved-EF (PEF: LVEF ≥ 50%) and reduced-EF (REF: LVEF< 5 0%) group by echocardiography. Platelet reactivity was measured using VerifyNow P2Y 12 assay and high platelet reactivity (HPR) was defined as PRU ≥ 252. The major adverse cardiac and cerebrovascular events (MACCEs) were a composite of death, myocardial infarction, stent thrombosis and stroke at 5 years after PCI. Major bleeding was defined as Bleeding Academic Research Consortium bleeding types 3–5. Results: A total of 13,160 patients from PTRG-DES, 9,319 (79.6%) patients with the results of both PRU and LVEF were analyzed. The incidence of MACCE and major bleeding was higher in REF group as compared with PEF group (MACCEs: hazard ratio [HR] 2.17, P < 0.001, 95% confidence interval [CI] 1.85–2.55; major bleeding: HR 1.78, P < 0.001, 95% CI 1.39–2.78).The highest rate of MACCEs was found in patients with REF and HPR, and the difference between the groups was statistically significant (HR 3.14 in REF(+)/HPR(+) vs. PEF(+)/HPR(-) group,P <0.01, 95% CI 2.51–3.91). The frequency of major bleeding was not associated with the HPR in either group. Conclusion LV dysfunction was associated with an increased incidence of MACCEs and major bleeding in patients who underwent PCI. The HPR status further exhibited significant increase of MACCEs in patients with LV dysfunction in a large, real-world registry.Trial Registration: ClinicalTrials.gov Identifier: NCT04734028

The outstanding development in contemporary medicine, highlighted by percutaneous coronary intervention (PCI), was achieved through the adoption of drug-eluting stents (DESs). Although DES is the established therapy for patients undergoing PCI for de novo coronary artery disease (CAD), their drawbacks include restenosis, stent thrombosis, and the requirement for dual antiplatelet therapy (DAPT) with an uncertain duration regarding its optimality. Drug-coated balloon (DCB) treatment leaves nothing behind on the vessel wall, providing the benefit of avoiding stent thrombosis and not necessitating obligatory extended DAPT. After optimizing coronary blood flow, DCB treatment delivers an antiproliferative drug directly coated on a balloon. Although more evidence is needed for the application of DCB treatment in de novo coronary lesions, recent studies suggest the safety and effectiveness of DCB treatment for diverse conditions including small and large vessel diseases, complex lesions like bifurcation lesions or diffuse or multivessel diseases, chronic total occlusion lesions, acute myocardial infarctions, patients at high risk of bleeding, and beyond. Consequently, we will review the current therapeutic choices for managing de novo CAD using DCB and assess the evidence supporting their concurrent application.Additionally, it aims to discuss future important perspectives.

Background/Aims: The genetic expression in the active inflammatory regions is increased in ulcerative colitis (UC) with endoscopic activity. The aim of this study was to investigate the molecular activity of inflammation and tissue remodeling markers in endoscopically inflamed and uninflamed regions of UC. Methods: Patients with UC (n=47) and controls (n=20) were prospectively enrolled at the Seoul National University Bundang Hospital. Inflamed tissue was obtained at the most active lesion, and uninflamed tissue was collected from approximately 15 cm above the upper end of the active lesion via colonoscopic biopsies. The messenger RNA expression levels of transforming growth factor β (TGF-β), interleukin (IL)-1β, IL-6, IL-17A, E-cadherin, olfactomedin-4 (OLFM4), leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), vimentin, fibroblast-specific protein-1 (FSP1), and α-smooth muscle actin (SMA) were evaluated. Mucosal healing (MH) was defined according to a Mayo endoscopic score of 0, 1 or non-MH (Mayo endoscopic score of 2 or 3). Results: The messenger RNA expressions of TGF-β, IL-1β, OLFM4, FSP1, vimentin, and α-SMA were significantly higher, and that of E-cadherin was significantly lower in inflamed and uninflamed regions of patients with UC than those in controls. In the inflamed regions, patients in the non-MH group had significantly increased genetic expression of TGF-β, FSP1, vimentin, and α-SMA compared to patients in the MH group. Similarly, the non-MH group had significantly higher genetic expression of TGF-β, IL-1β, IL-6, vimentin, and α-SMA than the MH group in the uninflamed regions. Conclusions Endoscopic activity in UC suggests inflammation and tissue remodeling of uninflamed regions similar to inflamed regions.

Background/Aims: The genetic expression in the active inflammatory regions is increased in ulcerative colitis (UC) with endoscopic activity. The aim of this study was to investigate the molecular activity of inflammation and tissue remodeling markers in endoscopically inflamed and uninflamed regions of UC. Methods: Patients with UC (n=47) and controls (n=20) were prospectively enrolled at the Seoul National University Bundang Hospital. Inflamed tissue was obtained at the most active lesion, and uninflamed tissue was collected from approximately 15 cm above the upper end of the active lesion via colonoscopic biopsies. The messenger RNA expression levels of transforming growth factor β (TGF-β), interleukin (IL)-1β, IL-6, IL-17A, E-cadherin, olfactomedin-4 (OLFM4), leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), vimentin, fibroblast-specific protein-1 (FSP1), and α-smooth muscle actin (SMA) were evaluated. Mucosal healing (MH) was defined according to a Mayo endoscopic score of 0, 1 or non-MH (Mayo endoscopic score of 2 or 3). Results: The messenger RNA expressions of TGF-β, IL-1β, OLFM4, FSP1, vimentin, and α-SMA were significantly higher, and that of E-cadherin was significantly lower in inflamed and uninflamed regions of patients with UC than those in controls. In the inflamed regions, patients in the non-MH group had significantly increased genetic expression of TGF-β, FSP1, vimentin, and α-SMA compared to patients in the MH group. Similarly, the non-MH group had significantly higher genetic expression of TGF-β, IL-1β, IL-6, vimentin, and α-SMA than the MH group in the uninflamed regions. Conclusions Endoscopic activity in UC suggests inflammation and tissue remodeling of uninflamed regions similar to inflamed regions.