Purpose: Although gastric cancer (GC) exhibits significant genomic heterogeneity, the clinical implications of its immune microenvironment remain poorly understood. Materials and Methods: We retrospectively evaluated patients with GC who underwent gastrectomies between 2011 and 2014. The tumors were analyzed for Epstein–Barr virus (EBV), microsatellite instability-high (MSI-H), tumor-infiltrating lymphocytes (CD3), tumor-associated macrophages (CD68 and CD163), and programmed death-ligand 1 (PD-L1) expression. Tumors were classified using the modified The Cancer Genome Atlas scheme, and their clinical characteristics were compared. Results: A total of 567 patients were classified into EBV (6%), MSI-H (10%), chromosomal instability-like (36%), and genomically stable-like (48%) subtypes. EBV tumors exhibited the highest PD-L1 expression (85%) and immune infiltration by CD3+ T cells (86%), CD68+ macrophages (58%), and CD163+ macrophages (40%). High CD68+ macrophage tumors were associated with advanced stages and worse 5-year disease-free survival (83% vs. 95%; P<0.001);however, this association was not independently significant after adjusting for the tumor-nodemetastasis stage. PD-L1 expression did not significantly affect the survival outcomes. Conclusions GC subtypes have distinct immune microenvironments that influence prognosis. Our findings highlight the prognostic and therapeutic potential of immune profiling in GC.

Background: There are limited long-term clinical outcome data comparing first-generation (1G) versus second-generation (2G) drug-eluting stents (DES) in patients with single-vessel disease (SVD). We sought to compare the efficacy and safety of 1G- and 2G-DES in SVD patients who underwent successful percutaneous coronary intervention (PCI) over 10 years of clinical follow-up. Methods: A total of 2,312 consecutive patients with SVD who underwent PCI with 1G-DES (paclitaxel- or sirolimus-eluting stents, n = 811) or 2G-DES (zotarolimus [Endeavor, Endeavor Resolute]- or everolimus-eluting stents [Promus Element, Xience], n = 1,082) were enrolled.After propensity score matching, 2 matched groups (538 pairs) were generated. Study endpoints included individual and composite clinical outcomes through 10 years. Results: During the 10-year follow-up, the 2G-DES group had lower incidences of myocardial infarction (MI; hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.22–0.92; P = 0.028) and target lesion revascularization (TLR; HR, 0.54; 95% CI, 0.32–0.91; P = 0.021) than the 1G-DES group. Rates of total death, cardiac death, non-target vessel revascularization, stroke, major adverse cardiac events, and major adverse cardiac and cerebrovascular events were similar between groups. Conclusions In our single-center, all-comer registry, 2G-DES were associated with lower incidence rates of MI and TLR compared to 1G-DES in SVD patients over 10 years of followup, indicating a safer and more durable effect than 1G-DES.

Background: Oral cancer drugs, particularly tyrosine kinase inhibitors (TKIs), are increasingly popular due to their convenience.However, they pose challenges like drug interactions, especially with medications like azole antifungals. While the FDA providessome guidance, more detailed information is needed to manage these interactions effectively. A meta-analysis was conducted tounderstand the impact of interactions between TKIs and azole antifungals on adverse events during clinical studies. Methods: A meta-analysis followed PRISMA guidelines. Data from PubMed, EMBASE, and references were searched until November 30, 2021. Inclusion criteria encompassed studies on TKI-antifungal interactions in English. Study selection and quality assessment were conducted by two independent investigators. Results: Out of 158 articles, 11 were selected for analysis. Combination therapy showed a slight increase in adverse events but was not statistically significant (OR 1.02, 95% CI 0.49-2.13, p=0.95). AUC and Cmax fold changes did not significantly impact adverse event development. Both itraconazole and ketoconazole showed no significant difference in adverse event development compared to TKI alone. Conclusions Study finds TKI-DDI not significantlylinked to AE increase; azole antifungal types not related to AE. Future DDI research crucial for drug development.

Background: Oral cancer drugs, particularly tyrosine kinase inhibitors (TKIs), are increasingly popular due to their convenience.However, they pose challenges like drug interactions, especially with medications like azole antifungals. While the FDA providessome guidance, more detailed information is needed to manage these interactions effectively. A meta-analysis was conducted tounderstand the impact of interactions between TKIs and azole antifungals on adverse events during clinical studies. Methods: A meta-analysis followed PRISMA guidelines. Data from PubMed, EMBASE, and references were searched until November 30, 2021. Inclusion criteria encompassed studies on TKI-antifungal interactions in English. Study selection and quality assessment were conducted by two independent investigators. Results: Out of 158 articles, 11 were selected for analysis. Combination therapy showed a slight increase in adverse events but was not statistically significant (OR 1.02, 95% CI 0.49-2.13, p=0.95). AUC and Cmax fold changes did not significantly impact adverse event development. Both itraconazole and ketoconazole showed no significant difference in adverse event development compared to TKI alone. Conclusions Study finds TKI-DDI not significantlylinked to AE increase; azole antifungal types not related to AE. Future DDI research crucial for drug development.

Background: Oral cancer drugs, particularly tyrosine kinase inhibitors (TKIs), are increasingly popular due to their convenience.However, they pose challenges like drug interactions, especially with medications like azole antifungals. While the FDA providessome guidance, more detailed information is needed to manage these interactions effectively. A meta-analysis was conducted tounderstand the impact of interactions between TKIs and azole antifungals on adverse events during clinical studies. Methods: A meta-analysis followed PRISMA guidelines. Data from PubMed, EMBASE, and references were searched until November 30, 2021. Inclusion criteria encompassed studies on TKI-antifungal interactions in English. Study selection and quality assessment were conducted by two independent investigators. Results: Out of 158 articles, 11 were selected for analysis. Combination therapy showed a slight increase in adverse events but was not statistically significant (OR 1.02, 95% CI 0.49-2.13, p=0.95). AUC and Cmax fold changes did not significantly impact adverse event development. Both itraconazole and ketoconazole showed no significant difference in adverse event development compared to TKI alone. Conclusions Study finds TKI-DDI not significantlylinked to AE increase; azole antifungal types not related to AE. Future DDI research crucial for drug development.

Background and Objectives: Ultimaster™, a third-generation sirolimus-eluting stent using biodegradable polymer, has been introduced to overcome long term adverse vascular events, such as restenosis or stent thrombosis. In the present study, we aimed to evaluate the 12-month clinical outcomes of Ultimaster™ stents in Korean patients with coronary artery disease. Methods: This study is a multicenter, prospective, observational registry across 12 hospitals. To reflect real-world clinical evidence, non-selective subtypes of patients and lesions were included in this study. The study end point was target lesion failure (TLF) (the composite of cardiac death, target vessel myocardial infarction [MI], and target lesion revascularization [TLR]) at 12-month clinical follow up. Results: A total of 576 patients were enrolled between November 2016 and May 2021. Most of the patients were male (76.5%), with a mean age of 66.0±11.2 years. Among the included patients, 40.1% had diabetes mellitus (DM) and 67.9% had acute coronary syndrome (ACS).At 12 months, the incidence of TLF was 4.1%. The incidence of cardiac death was 1.5%, MI was 1.0%, TLR was 2.7%, and stent thrombosis was 0.6%. In subgroup analysis based on the presence of ACS, DM, hypertension, dyslipidemia, or bifurcation, there were no major differences in the incidence of the primary endpoint. Conclusions The present registry shows that Ultimaster™ stent is safe and effective for routine real-world clinical practice in non-selective Korean patients, having a low rate of adverse events at least up to 12 months.

BACKGROUND: Exosomes, nano-sized vesicles ranging between 30 and 150 nm secreted by human cells, play a pivotal role in long-range intercellular communication and have attracted significant attention in the field of regenerative medicine. Nevertheless, their limited productivity and cost-effectiveness pose challenges for clinical applications. These issues have recently been addressed by cell-derived nanovesicles (CDNs), which are physically synthesized exosome-mimetic nanovesicles from parent cells, as a promising alternative to exosomes. CDNs exhibit structural, physical, and biological properties similar to exosomes, containing intracellular protein and genetic components encapsulated by the cell plasma membrane. These characteristics allow CDNs to be used as regenerative medicine and therapeutics on their own, or as a drug delivery system. METHODS: The paper reviews diverse methods for CDN synthesis, current analysis techniques, and presents engineering strategies to improve lesion targeting efficiency and/or therapeutic efficacy. RESULTS: CDNs, with their properties similar to those of exosomes, offer a cost-effective and highly productive alternative due to their non-living biomaterial nature, nano-size, and readiness for use, allowing them to overcome several limitations of conventional cell therapy methods. CONCLUSION Ongoing research and enhancement of CDNs engineering, along with comprehensive safety assessments and stability analysis, exhibit vast potential to advance regenerative medicine by enabling the development of efficient therapeutic interventions.

Background: Oral cancer drugs, particularly tyrosine kinase inhibitors (TKIs), are increasingly popular due to their convenience.However, they pose challenges like drug interactions, especially with medications like azole antifungals. While the FDA providessome guidance, more detailed information is needed to manage these interactions effectively. A meta-analysis was conducted tounderstand the impact of interactions between TKIs and azole antifungals on adverse events during clinical studies. Methods: A meta-analysis followed PRISMA guidelines. Data from PubMed, EMBASE, and references were searched until November 30, 2021. Inclusion criteria encompassed studies on TKI-antifungal interactions in English. Study selection and quality assessment were conducted by two independent investigators. Results: Out of 158 articles, 11 were selected for analysis. Combination therapy showed a slight increase in adverse events but was not statistically significant (OR 1.02, 95% CI 0.49-2.13, p=0.95). AUC and Cmax fold changes did not significantly impact adverse event development. Both itraconazole and ketoconazole showed no significant difference in adverse event development compared to TKI alone. Conclusions Study finds TKI-DDI not significantlylinked to AE increase; azole antifungal types not related to AE. Future DDI research crucial for drug development.

Background and Objectives: Zonulin is a human protein that regulates intercellular tight junctions and increases the permeability of the intestinal epithelium. In light of the increasing focus on zonulin’s role in numerous chronic inflammatory diseases, this study aimed to investigate whether differences exist in serum zonulin levels and bronchial epithelium zonulin expression in vivo between asthma and normal groups, using a mouse model. Methods: Sixteen mice were utilized in this study, divided evenly between the normal and asthma groups. Serum zonulin levels, the expression of zonulin antibody in the bronchial epithelium, and serum cytokine levels were evaluated in both groups. Enzyme-linked immunosorbent assay and RNA in situ hybridization were utilized for the analysis. Results: The asthma group exhibited significantly higher levels of serum zonulin. High zonulin antibody expression was also observed in the bronchial epithelium of the asthma group. Given that our mouse model demonstrated a significant difference in interleukin (IL)-4 and IL-6 between the normal and asthma groups, zonulin may be associated not only with type 2 responses but also with various subtypes of asthma. Further studies are required to investigate this relationship in greater detail. Conclusion Zonulin may play a role in the complex pathophysiology of asthma and could serve as a biomarker in various asthma-related situations.

BACKGROUND/OBJECTIVES: This study analyzed the quality of lunches provided in senior leisure service (SLS) facilities and compared institutional foodservice (IF) and noninstitutional foodservice (non-IF). SUBJECTS/METHODS: Data of 390 adults aged 65 years or older who ate lunches in SLS facilities were analyzed using the information from the 2013–2017 Korea National Health and Nutrition Examination Survey. The participants were classified into IF (n = 129) and non-IF (n = 261) groups according to meal type provided. The intake of major food groups, energy and nutrients, and nutrient adequacy ratio (NAR) and mean adequacy ratio (MAR) were analyzed. The diversity of meals was evaluated by food group patterns, dietary diversity score (DDS) and dietary variety score (DVS). Energy intake was adjusted in model 1, while energy and sex were adjusted in model 2. All confounding variables were adjusted in model 3. RESULTS: The intake of seafoods (P < 0.001 in models 1, 2, and 3), seaweeds (P < 0.01 in models 1 and 2), and dairy products (P < 0.05 in models 1, 2, and 3) was significantly higher in the IF group. No significant difference existed in energy intake; however, the intake of all nutrients except carbohydrate and vitamin C was significantly higher in the IF group. NAR of all nutrients, excluding vitamin C, was higher in the IF group, and MAR was also higher in the IF group (P < 0.001 in models 1, 2, and 3). The IF group had significantly higher DDS and DVS than the non-IF group (P < 0.001). CONCLUSIONS The lunches provided in SLS facilities were better in terms of quantity and quality when provided through IF than through non-IF. More systematic foodservice programs should be implemented in SLS facilities, especially in facilities wherein users prepare their own meals.