20260 research outputs found
Sort by
Safety, Tolerability, Pharmacokinetics, and pharmacodynamics of YH35324, a novel Long-Acting High-Affinity IgETrap-Fc protein in subjects with Atopy: Results from the First-in-Human study
Get PDFBackground: YH35324, a long-acting IgETrap-Fc fusion protein, is a novel therapeutic agent for immunoglobulin E (IgE)-mediated allergic diseases. This randomized, double-blind, placebo/active-controlled, single ascending dose Phase 1 study assessed the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of YH35324 in subjects with atopy. Methods: Eligible subjects were healthy subjects or atopic adults with mild allergic rhinitis, atopic dermatitis, food allergy, or urticaria, and a serum total IgE level of 30–700 IU/mL (Part A) or > 700 IU/mL (Part B). In Part A, 35 subjects in 5 cohorts received YH35324 (0.3, 1, 3, 6, and 9 mg/kg), 8 received omalizumab (300 mg), and 9 received placebo. In Part B, 8 subjects received YH35324 and 8 received omalizumab. Results: Twenty subjects (38.5 %) in Part A (YH35324: 37.1 %, omalizumab: 50.0 %, placebo: 33.3 %) and 10 subjects (62.5 %) in Part B (YH35324: 100 %; omalizumab: 25.0 %) experienced treatment-emergent adverse events (TEAEs). TEAEs were mostly grade 1/2; no serious AEs, AE-related treatment discontinuation, or anaphylaxis were reported. YH35324 exhibited dose-proportional increase in Cmax and AUClast over the dose range of 0.3–9 mg/kg. YH35324 rapidly suppressed serum-free IgE levels to a significant extent (< 25 and < 82.8 ng/mL, both P < 0.05) and with longer duration than omalizumab. Conclusion: This study showed that YH35324 has a favorable safety profile and is effective in reducing serum-free IgE levels in subjects with atopic conditions
Deep learning-based metastasis detection in patients with lung cancer to enhance reproducibility and reduce workload in brain metastasis screening with MRI: a multi-center study
Get PDFObjectives: To assess whether a deep learning-based system (DLS) with black-blood imaging for brain metastasis (BM) improves the diagnostic workflow in a multi-center setting. Materials and methods: In this retrospective study, a DLS was developed in 101 patients and validated on 264 consecutive patients (with lung cancer) having newly developed BM from two tertiary university hospitals, which performed black-blood imaging between January 2020 and April 2021. Four neuroradiologists independently evaluated BM either with segmented masks and BM counts provided (with DLS) or not provided (without DLS) on a clinical trial imaging management system (CTIMS). To assess reading reproducibility, BM count agreement between the readers and the reference standard were calculated using limits of agreement (LoA). Readers’ workload was assessed with reading time, which was automatically measured on CTIMS, and were compared between with and without DLS using linear mixed models considering the imaging center. Results: In the validation cohort, the detection sensitivity and positive predictive value of the DLS were 90.2% (95% confidence interval [CI]: 88.1–92.2) and 88.2% (95% CI: 85.7–90.4), respectively. The difference between the readers and the reference counts was larger without DLS (LoA: −0.281, 95% CI: −2.888, 2.325) than with DLS (LoA: −0.163, 95% CI: −2.692, 2.367). The reading time was reduced from mean 66.9 s (interquartile range: 43.2–90.6) to 57.3 s (interquartile range: 33.6–81.0) (P <.001) in the with DLS group, regardless of the imaging center. Conclusion: Deep learning-based BM detection and counting with black-blood imaging improved reproducibility and reduced reading time, on multi-center validation
Obesity in Children and Adolescents: 2022 Update of Clinical Practice Guidelines for Obesity by the Korean Society for the Study of Obesity
Get PDFThe prevalence of obesity in children and adolescents has been gradually increasing in recent years and has become a major health problem. Childhood obesity can readily progress to adult obesity. It is associated with obesity-related comorbidities, such as type 2 diabetes mellitus, hypertension, obstructive sleep apnea, non-alcoholic fatty liver disease, and the risk factor for cardiovascular disease. It is important to make an accurate assessment of overweight and obesity in children and adolescents with consideration of growth and development. Childhood obesity can then be prevented and treated using an appropriate treatment goal and safe and effective treatment strategies. This article summarizes the clinical practice guidelines for obesity in children and adolescents that are included in the 8th edition of the Clinical Practice Guidelines for Obesity of the Korean Society for the Study of Obesity
Challenges and potential improvements in the Accreditation Standards of the Korean Institute of Medical Education and Evaluation 2019 (ASK2019) derived through meta-evaluation: a cross-sectional study
Get PDFPURPOSE: This study aimed to identify challenges and potential improvements in Korea's medical education accreditation process according to the Accreditation Standards of the Korean Institute of Medical Education and Evaluation 2019 (ASK2019). Meta-evaluation was conducted to survey the experiences and perceptions of stakeholders, including self-assessment committee members, site visit committee members, administrative staff, and medical professors. METHODS: A cross-sectional study was conducted using surveys sent to 40 medical schools. The 332 participants included self-assessment committee members, site visit team members, administrative staff, and medical school professors. The t-test, one-way analysis of variance and the chi-square test were used to analyze and compare opinions on medical education accreditation between the categories of participants. RESULTS: Site visit committee members placed greater importance on the necessity of accreditation than faculty members. A shared positive view on accreditation's role in improving educational quality was seen among self-evaluation committee members and professors. Administrative staff highly regarded the Korean Institute of Medical Education and Evaluation's reliability and objectivity, unlike the self-evaluation committee members. Site visit evaluators positively perceived the clarity of accreditation standards, differing from self-assessment committee members. Administrative staff were most optimistic about implementing standards. However, the accreditation process encountered challenges, especially in duplicating content and preparing self-evaluation reports. Finally, perceptions regarding the accuracy of final site visit reports varied significantly between the self-evaluation committee members and the site visit committee members. CONCLUSION: This study revealed diverse views on medical education accreditation, highlighting the need for improved communication, expectation alignment, and stakeholder collaboration to refine the accreditation process and quality
Real-world treatment patterns and clinical outcomes in patients with stage III NSCLC in Korea: The KINDLE study
Get PDFObjective: KINDLE-Korea is part of a real-world KINDLE study that aimed to characterize the treatment patterns and clinical outcomes of patients with stage III non-small cell lung cancer (NSCLC). Materials and Methods: The KINDLE was an international real-world study that explores patient and disease characteristics, treatment patterns, and survival outcomes. The KINDLE-Korea included stage III NSCLC patients diagnosed between January 2013 and December 2017. Results: A total of 461 patients were enrolled. The median age was 66 years (range: 24–87). Most patients were men (75.7%) with a history of smoking (74.0%), stage IIIA NSCLC (69.2%), and unresectable disease (52.9%). A total of 24.3% had activating EGFR mutation and 62.2% were positive for PDL1 expression. Broadly categorized, 44.6% of the patients received chemoradiation (CRT)-based therapy, 35.1% underwent surgery, and 20.3% received palliative therapies as initial treatment. The most commonly adopted approaches for patients with stage IIIA and IIIB disease were surgery and CRT, respectively. The median PFS was 15.2 months and OS was 66.7 months. Age >65 years, adenocarcinoma histology, and surgery as the initial treatment were significantly associated with longer OS. Conclusion: This study revealed the heterogeneity of treatment patterns and survival outcomes in patients with stage III NSCLC before durvalumab consolidation came into clinical practice. There is an unmet need for patients who are not eligible for surgery as an initial therapy. Novel therapeutic approaches are highly warranted to improve clinical outcomes
Review of COVID-19 Therapeutics by Mechanism: From Discovery to Approval
Get PDFThe global research and pharmaceutical community rapidly mobilized to develop treatments for coronavirus disease 2019 (COVID-19). Existing treatments have been repurposed and new drugs have emerged. Here we summarize mechanisms and clinical trials of COVID-19 therapeutics approved or in development. Two reviewers, working independently, reviewed published data for approved COVID-19 vaccines and drugs, as well as developmental pipelines, using databases from the following organizations: United States Food and Drug Administration (US-FDA), European Medicines Agency (EMA), Japanese Pharmaceutical and Medical Devices Agency (PMDA), and ClinicalTrials.gov. In all, 387 drugs were found for initial review. After removing unrelated trials and drugs, 66 drugs were selected, including 17 approved drugs and 49 drugs under development. These drugs were classified into six categories: 1) drugs targeting the viral life cycle 2) Anti-severe acute respiratory syndrome coronavirus 2 Monoclonal Antibodies, 3) immunomodulators, 4) anti-coagulants, 5) COVID-19-induced neuropathy drugs, and 6) other therapeutics. Among the 49 drugs under development are the following: 6 drugs targeting the viral life cycle, 12 immunosuppression drugs, 2 immunostimulants, 2 HIF-PHD targeting drugs, 3 GM-CSF targeting drugs, 5 anti-coagulants, 2 COVID-19-induced neuropathy drugs, and 17 others. This review provides insight into mechanisms of action, properties, and indications for COVID-19 medications
Nomogram for predicting in-hospital mortality in trauma patients undergoing resuscitative endovascular balloon occlusion of the aorta: a retrospective multicenter study
Get PDFRecently, resuscitative endovascular balloon occlusion of the aorta (REBOA) had been introduced as an innovative procedure for severe hemorrhage in the abdomen or pelvis. We aimed to investigate risk factors associated with mortality after REBOA and construct a model for predicting mortality. This multicenter retrospective study collected data from 251 patients admitted at five regional trauma centers across South Korea from 2015 to 2022. The indications for REBOA included patients experiencing hypovolemic shock due to hemorrhage in the abdomen, pelvis, or lower extremities, and those who were non-responders (systolic blood pressure (SBP) < 90 mmHg) to initial fluid treatment. The primary and secondary outcomes were mortality due to exsanguination and overall mortality, respectively. After feature selection using the least absolute shrinkage and selection operator (LASSO) logistic regression model to minimize overfitting, a multivariate logistic regression (MLR) model and nomogram were constructed. In the MLR model using risk factors selected in the LASSO, five risk factors, including initial heart rate (adjusted odds ratio [aOR], 0.99; 95% confidence interval [CI], 0.98–1.00; p = 0.030), initial Glasgow coma scale (aOR, 0.86; 95% CI 0.80–0.93; p < 0.001), RBC transfusion within 4 h (unit, aOR, 1.12; 95% CI 1.07–1.17; p < 0.001), balloon occlusion type (reference: partial occlusion; total occlusion, aOR, 2.53; 95% CI 1.27–5.02; p = 0.008; partial + total occlusion, aOR, 2.04; 95% CI 0.71–5.86; p = 0.187), and post-REBOA systolic blood pressure (SBP) (aOR, 0.98; 95% CI 0.97–0.99; p < 0.001) were significantly associated with mortality due to exsanguination. The prediction model showed an area under curve, sensitivity, and specificity of 0.855, 73.2%, and 83.6%, respectively. Decision curve analysis showed that the predictive model had increased net benefits across a wide range of threshold probabilities. This study developed a novel intuitive nomogram for predicting mortality in patients undergoing REBOA. Our proposed model exhibited excellent performance and revealed that total occlusion was associated with poor outcomes, with post-REBOA SBP potentially being an effective surrogate measure
Imeglimin attenuates NLRP3 inflammasome activation by restoring mitochondrial functions in macrophages
Get PDFImeglimin is a novel oral antidiabetic drug for treating type 2 diabetes. However, the effect of imeglimin on NLRP3 inflammasome activation has not been investigated yet. Here, we aimed to investigate whether imeglimin reduces LPS-induced NLRP3 inflammasome activation in THP-1 macrophages and examine the associated underlying mechanisms. We analyzed the mRNA and protein expression levels of NLRP3 inflammasome components and IL-1β secretion. Additionally, reactive oxygen species (ROS) generation, mitochondrial membrane potential, and mitochondrial permeability transition pore (mPTP) opening were measured by flow cytometry. Imeglimin inhibited NLRP3 inflammasome-mediated IL-1β production in LPS-stimulated THP-1-derived macrophages. In addition, imeglimin reduced LPS-induced mitochondrial ROS production and mitogen-activated protein kinase phosphorylation. Furthermore, imeglimin restored the mitochondrial function by modulating mitochondrial membrane depolarization and mPTP opening. We demonstrated for the first time that imeglimin reduces LPS-induced NLRP3 inflammasome activation by inhibiting mPTP opening in THP-1 macrophages. These results suggest that imeglimin could be a promising new anti-inflammatory agent for treating diabetic complications