Objective: This study aimed to develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantify gentamicin residues in milk and to establish a withdrawal period for an intramuscular gentamicin product in dairy cows. Methods: Nine Holstein cows received a gentamicin product (50 mg gentamicin sulfate/ mL) at 0.1 mL/kg twice daily at 12 h intervals via intramuscular injection. Milk samples were collected before dosing and at 12 h intervals up to 168 h after the final administration and analysed with a validated LC-MS/MS method using heptafluorobutyric acid as an ion-pairing reagent. Results: The method showed recovery rates of 86%–104%, coefficients of variation of 3%–11%, and limits of detection and quantitation of 23 and 70 ng/mL, respectively. Mean gentamicin concentrations exceeded the maximum residue limit (MRL; 0.2 mg/kg) at 12 h during treatment and 12 h after the final administration, and were < MRL in all cows from 36 h after the last dose. Based on residue depletion data and a national non-statistical guideline, a withdrawal period of 40–48 h was derived, and the regulatory withdrawal period for this product was established as 3 days. Conclusions and Relevance: The validated LC-MS/MS method enables rapid quantitation of gentamicin residues in bovine milk. A 3-day regulatory withdrawal period for this product supports milk safety, regulatory compliance, and practical use in dairy herds.

Objective: To evaluate the association between atopic dermatitis (AD) and suicidal behaviors in adolescent defectors among residents who escaped from North Korean (adolescent defectors, n=423) and adolescents with South Korean parents (Korean adolescents, n=540,265). Methods: The study used data from the Korea Youth Risk Behavior Survey conducted from 2011 to 2019. Differences in general characteristics, health behaviors, suicidal ideation, suicide plans, suicide attempts, and AD between adolescent defectors and Korean adolescents were examined. Multiple logistic regression analysis was used to determine the association between AD and suicidal behaviors. Results: The adolescent defectors group had lower AD (16.3% vs. 24.2%), poorer subjective health (10% vs. 6%), smoked more (47% vs. 18%), drank more (60% vs. 43%), lived with family less frequently (56% vs. 96%), and were more than twice as likely to have depression (42% vs. 27%), suicidal ideation (30% vs. 14%), a suicide plan (23% vs. 5%), or have made a prior suicide attempt (19% vs. 3%) compared with the Korean adolescent group (p<0.001). The adjusted odds ratio for the adolescent defectors group compared to the Korean adolescent group was 1.66 for suicidal ideation, 3.59 for suicide plans, and 4.34 for suicide attempts (p<0.001). AD was found to be associated with suicide plans and attempts in adolescent defectors and associated with suicidal ideation in Korean adolescents. Conclusion AD was significantly associated with suicide plans and suicidal attempts among adolescent defectors and suicidal ideation in Korean adolescents, based on a random sample of middle- and high-school students.

Purpose: Programmed death-1 blockade with pembrolizumab has shown promising activity in relapsed/refractory (R/R) extranodal natural killer/T-cell lymphoma (NKTCL), but studies are limited, with small patient numbers. Materials and Methods: Thirteen institutes involved with the Consortium for Improving Survival of Lymphoma, a Korean lymphoma study group, collected the clinical data of 59 patients treated with pembrolizumab as salvage therapy between 2016 and 2022. Results: The median age of the patients was 60 years (range, 22 to 87 years), and 76.3% had advanced Ann Abor stage disease. Pembrolizumab was given to 35.6%, 40.7%, and 23.7% of the patients as second-, third-, and fourth- or higher-line chemotherapy, respectively. The overall response rate was 40.7%, with 28.8% having complete response. The estimated 2-year progression-free survival (PFS) and overall survival rates for all patients were 21.5% and 28.7%, respectively; for responders, the rates were 53.0% and 60.7%, respectively. Although not statistically significant, Eastern Cooperative Oncology Group performance status ≥ 2 (hazard ratio [HR], 1.91; 95% confidence interval [95% CI], 0.93 to 3.94; p=0.078) and stage III or IV disease (HR, 2.59; 95% CI, 0.96 to 6.96; p=0.060) were associated with a trend toward shorter PFS in multivariate analysis. Grade 3 or 4 adverse events (AEs) were noted in 12 patients (20.3%); neutropenia (10.2%), fatigue (6.8%), and pneumonitis (5.1%) were most common AEs. Conclusion In conclusion, while pembrolizumab had a modest effect on patients with R/R NKTCL, it may be a useful salvage therapy for patients with localized disease and good performance status.

Background: Type 2 diabetes mellitus (T2DM) induces endothelial dysfunction and inflammation, which are the main factors for atherosclerosis and cardiovascular disease. The present study aimed to compare the effects of rosuvastatin monotherapy and rosuvastatin/ezetimibe combination therapy on lipid profile, insulin sensitivity, and vascular inflammatory response in patients with T2DM. Methods: A total of 101 patients with T2DM and dyslipidemia were randomized to either rosuvastatin monotherapy (5 mg/day, n=47) or rosuvastatin/ezetimibe combination therapy (5 mg/10 mg/day, n=45) and treated for 12 weeks. Serum lipids, glucose, insulin, soluble intercellular adhesion molecule-1 (sICAM-1), and peroxiredoxin 4 (PRDX4) levels were determined before and after 12 weeks of treatment. Results: The reduction in low density lipoprotein cholesterol (LDL-C) by more than 50% from baseline after treatment was more in the combination therapy group. The serum sICAM-1 levels increased significantly in both groups, but there was no difference between the two groups. The significant changes in homeostasis model assessment of insulin resistance (HOMA-IR) and PRDX4 were confirmed only in the subgroup in which LDL-C was reduced by 50% or more in the combination therapy group. However, after adjusting for diabetes mellitus duration and hypertension, the changes in HOMA-IR and PRDX4 were not significant between the two groups. Conclusion Although rosuvastatin/ezetimibe combination therapy had a greater LDL-C reduction effect than rosuvastatin monotherapy, it had no additional effects on insulin sensitivity and vascular inflammatory response. Further studies are needed on the effect of long-term treatment with ezetimibe on insulin sensitivity and vascular inflammatory response.

Drug-induced liver injury (DILI) is considered to be a significant cause of drug wastage. Tomitigate clinical DILI risks, assessing drugs using human liver models is crucial since animal studies may fall short due to species-specific liver pathway variations. Cell-based preclinical hepatotoxicity testing is often pertinent. In the present study, cells from a human liver cancer line (HepG2 and HepaRG) were cultured in both formats of 2D and 3D spheroids to explore their responses to drugs. Liver-specific marker expressions across cell lines and culture formats were also examined to assess disparities in DILI marker expressions. After treating each cell with the drugs, cytotoxicity and liver injury markers aspartate aminotransferase and alanine aminotransferase were increased. In addition, liver specific markers albumin and urea decreased in a drug concentration-dependent manner. These findings were consistent with drug sensitivity. Additionally, mRNA expression levels of cytochrome P450 enzymes (CYPs) involved in hepatocellular drug metabolism were compared following treatment with enzyme inducers. CYP1A2 and CYP2C9 were not epxressed in HepG2 cells. HepaRG cells exhibited significantly increased expression of CYP1A2, 2C9, and 3A4 post-treatment. No-tably, enzyme expression was notably higher in 3D cultures than in 2D cultures. Collectively, these findings suggest that HepaRG cells and 3D cultures hold promise for evaluating DILI during early-stage drug development.

Purinergic P2Y Receptor Antagonists ; Consensus ; Cardiovascular System ; Cardiology ; Asia

Purpose: This study aimed to develop an intentional rounding protocol to enhance the clinical competence of nursing students. Methods: An intentional rounding protocol for nursing students’ clinical practice was developed following the ADDIE (Analysis, Design, Development, Implementation, and Evaluation) model. A convenient sampling method was used to select 23 junior year university nursing students during their clinical practice in adult nursing. The program evaluation included a quantitative assessment (communication and relationship efficacy, empathy, and patient safety competency) and focus group interviews. Results: The intentional rounding protocol focused on the 4Ps (pain, position, potty, and possessions) and encompassed aspects such as level of consciousness, pain management, personal care needs, intravenous injection, oxygen administration, nasogastricasoenteric tube care, maintenance of urine collection bags, and the identification of environmental fall risks. Nursing students performed intentional rounding at least twice a day. Following the implementation of this protocol, nursing students demonstrated a significant improvement in communication and interpersonal efficacy. The focus group interviews revealed four main themes: growth of human relationships, acquiring knowledge in and about the clinical field, becoming a nurse, and barriers in reality. Conclusion The intentional rounding protocol has the potential to enhance nursing students’ communication and interpersonal skills during clinical practice and to provide them with positive experiences in nursing clinical education. Therefore, it is recommended that this protocol be incorporated into nursing clinical practice education.

Background: Brentuximab vedotin (BV), a potent antibody-drug conjugate, targets the CD30 antigen.In Korea, BV has been approved for the treatment of relapsed or refractory Hodgkin lymphoma (HL), anaplastic large-cell lymphoma (ALCL), and cutaneous T-cell lymphomas, including mycosis fungoides (MF). However, there are limited data reflecting real-world experiences with BV treatment for HL, ALCL, and MF. Methods: This was a multicenter, non-interventional registry study of the efficacy and safety of BV in patients with relapsed or refractory CD30-positive lymphoma (CISL1803/BRAVO).Outcomes were determined based on the occurrence of relapse or progression and overall survival after BV treatment. Results: A total of 85 patients were enrolled in this study. The median number of BV cycles was 10 (range, 2‒16) in the patients with HL. The objective response rate (ORR) of patients with HL to BV was 85.4% (41/48), comprising 27 complete responses (CRs) and 14 partial responses (PRs). The ORR of ALCL was 88% (22/25), consisting of 17 CRs and five PRs, whereas the ORR of MF was 92% (11/12). At the median follow-up of 44.6 months after BV treatment, the median post-BV progression-free survival of HL, ALCL, and MF patients was 23.6 months, 29.0 months, and 16.7 months, respectively (P =0.641). The most common side effect of BV was peripheral neuropathy; 22 patients (25.9%, 22/85) experienced peripheral neuropathy (all grades). Conclusion The treatment outcomes of patients with relapsed or refractory CD30-positive lymphoma improved with BV treatment, and the safety profile was manageable.

Interstitial lung disease (ILD) involves persistent inflammation and fibrosis, leading to respiratory failure and even death. Adult tissue-derived mesenchymal stem cells (MSCs) show potential in ILD therapeutics but obtaining an adequate quantity of cells for drug application is difficult. Daewoong Pharmaceutical’s MSCs (DW-MSCs) derived from embryonic stem cells sustain a high proliferative capacity following long-term culture and expansion. The aim of this study was to investigate the therapeutic potential of DW-MSCs in experimental mouse models of ILD. DW-MSCs were expanded up to 12 passages for in vivo application in bleomycin-induced pulmonary fibrosis and collagen-induced connective tissue diseaseILD mouse models. We assessed lung inflammation and fibrosis, lung tissue immune cells, fibrosis-related gene/protein expression, apoptosis and mitochondrial function of alveolar epithelial cells, and mitochondrial transfer ability. Intravenous administration of DWMSCs consistently improved lung fibrosis and reduced inflammatory and fibrotic markers expression in both models across various disease stages. The therapeutic effect of DW-MSCs was comparable to that following daily oral administration of nintedanib or pirfenidone.Mechanistically, DW-MSCs exhibited immunomodulatory effects by reducing the number of B cells during the early phase and increasing the ratio of Tregs to Th17 cells during the late phase of bleomycin-induced pulmonary fibrosis. Furthermore, DW-MSCs exhibited antiapoptotic effects, increased cell viability, and improved mitochondrial respiration in alveolar epithelial cells by transferring their mitochondria to alveolar epithelial cells. Our findings indicate the strong potential of DW-MSCs in the treatment of ILD owing to their high efficacy and immunomodulatory and anti-apoptotic effects.

Background: Gestational diabetes mellitus (GDM) is the most common metabolic complication of pregnancy. To define the altered pathway in GDM placenta, we investigated the transcriptomic profiles from human placenta between GDM and controls. Methods: Clinical parameters and postpartum complications were reviewed in all participants.Differentially expressed canonical pathways were analyzed between the GDM and control groups based on transcriptomic analysis. CD4 + T, CD8 + T, and senescent T cell subsets were determined by flow cytometry based on staining for specific intracellular cytokines. Results: Gene ontology analysis revealed that the placenta of GDM revealed upregulation of diverse mitochondria or DNA replication related pathways and downregulation of T-cell immunity related pathways. The maternal placenta of the GDM group had a higher proportion of CD4 + T and CD8 + T cells than the control group. Interestingly, senescent CD4 + T cells tended to increase and CD8 + T cells were significantly increased in GDM compared to controls, along with increased programmed cell death-1 (CD274 + ) expression. Programmed death-ligand 1 expression in syncytotrophoblasts was also significantly increased in patients with GDM. Conclusion This study demonstrated increased proinflammatory T cells, senescent T cells and immune-check point molecules in GDM placentas, suggesting that changes in senescent T cells and immune-escape signaling might be related to the pathophysiology of GDM.