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Characterising infusion/injection-related reactions in patients with rheumatoid arthritis treated with biologic agents
No full textOBJECTIVES: Biologic disease-modifying anti-rheumatic drugs (bDMARDs) have transformed the management of rheumatoid arthritis (RA), but their efficacy can be limited by infusion/injection-related reactions (IRRs). This study investigated demographic and clinical factors associated with IRRs in patients with RA using data from the Korean College of Rheumatology Biologics & Targeted Therapy (KOBIO) Registry. METHODS: We analysed 1,832 patients with RA, categorising them into IRR and non-IRR groups. Demographic, disease characteristics, and treatment histories were compared. A Sankey plot visualised bDMARD switching patterns, and multivariable logistic regression identified IRR-independent predictors. RESULTS: IRRs occurred in 9.7% of patients and were significantly associated with younger age (mean 49.9 vs. 54.9 years; OR=1.793, p=0.014), secondary Sjogren's syndrome (OR=2.175, p=0.035), and prior leflunomide use (OR=1.497, p=0.015). Abatacept (OR=0.263, p<0.001), tocilizumab (OR=0.419, p<0.001), and golimumab (OR=0.345, p=0.006) were associated with reduced IRR risk compared to infliximab. Following IRRs, use of etanercept, infliximab, and adalimumab declined, while tocilizumab and Janus kinase (JAK) inhibitors increased. CONCLUSIONS: IRRs are common among RA patients receiving bDMARDs, particularly in younger individuals or those with prior leflunomide use. Abatacept, tocilizumab, and JAK inhibitors represent safer alternatives, underscoring the need for individualised treatment strategies
Use of a Reentry Device for Endovascular Recanalization of Central Venous Occlusions Associated With Failing Hemodialysis Access
No full textINTRODUCTION: To evaluate the technical feasibility and safety of a reentry device for endovascular recanalization of central venous occlusions associated with dysfunctional arteriovenous fistulas. METHODS: Between January 2013 and December 2023, 20 patients (13 women; mean age, 61.1 years) with dysfunctional fistulas attributed to central venous occlusion underwent treatment using an Outback LTD reentry device. All patients had experienced unsuccessful recanalization attempts using conventional endovascular techniques. Symptoms included increased venous pressure during hemodialysis (N = 8), arm swelling (N = 8), absence of flow (N = 1), graft thrombosis (N = 2), and maturation failure (N = 1). The mean age of the fistulas was 56.1 months, and 11 patients had a history of angioplasty. An Outback LTD reentry device was used when conventional endovascular techniques were unsuccessful. FINDINGS: Occlusions were observed at the junction of the subclavian and innominate veins (N = 15) and in the right innominate vein (N = 2), subclavian vein (N = 1), and axillary vein of the arm (N = 2). The reentry device was introduced via the fistula (N = 11), femoral vein (N = 8), or internal jugular vein (N = 1). Technical success was achieved in 18 patients (90.0%), all of whom successfully underwent hemodialysis. Eight patients with arm swelling experienced symptom relief. In the 14 patients available for long-term follow-up, the mean intervention-free period was 5.0 months, and the mean functional period of the fistula, with or without subsequent endovascular treatment, was 23.0 months. No complications were observed. DISCUSSION: An Outback reentry device may be used for central venous occlusions when conventional techniques are unsuccessful
Integrative multi-omics deciphers the potential mechanism and microbial biomarkers for lymph node metastasis in colorectal cancer
No full textUnderstanding and accurate diagnosis of lymph node metastasis (LNM) for patients with colorectal cancer (CRC) is essential to determine treatment and follow-up strategies. Therefore, in this study, we aimed to elucidate the biological process and identify the potential biomarker for LNM in CRC.A total of 30 patients who received a histologically confirmed diagnosis of CRC with Stage I to III and a curative surgery between November 2020 and July 2021 at Kyung Hee university hospital at Gangdong were included. We performed multi-omics approach integrating the data on somatic mutation, transcriptomic expression, DNA methylation, and microbiome with tumor and adjacent matched normal tissues of each patient. In total, 12 significant DEGs between the patients with and without LNM were identified, consisting of significantly upregulated S100A8 gene, a proinflammatory gene. The GSEA revealed that gene sets involving "MULTI CANCER INVASIVENESS" in terms related to epithelial-mesenchymal transition was significantly upregulated in the patients with LNM. Integrated functional analysis of DNA methylation with transcriptome profile shows that significantly hypomethylated promoters of the genes are enriched for LNM. The phylum Proteobacteria, unassigned (p_PU) presented significantly higher proportions in cancer tissues from the adjacent normal tissues. Notably, when compared to the patients without LNM, the gut microbiota of those with LNM appears to exhibit a significantly lower abundance of the p_PU, indicating its potential as promising biomarker for LNM in CRC. We explained the mechanism of tumor spreading using multi-omics analysis and identified the relevant metagenomic biomarker to predict the LNM in CRC by the recognition of host-microbial interaction, thereby can make the cancer surveillance of the patients more individualized and convincing
Surgical outcomes of Ahmed valve implantation with mitomycin C in glaucoma with and without high myopia
No full textBACKGROUND: This study aimed to assess the surgical outcomes of Ahmed glaucoma valve (AGV) implantation in high myopic eyes (axial length [AL] of >/= 26.0 mm) and to determine whether high myopia independently poses a risk of surgical failure. METHODS: We retrospectively reviewed 68 eyes from 59 patients with refractory glaucoma who underwent AGV implantation. Eyes were categorised into high myopia (23 eyes, 33.8%) and control (45 eyes, 66.2%) groups. The primary outcome was the surgical success rate, defined as postoperative intraocular pressure (IOP) of 6-21 mmHg or a >/= 20% reduction from baseline. Surgical success was further classified into criterion A (postoperative IOP /= 26 mm was a significant risk factor for surgical failure under both criterion A (hazard ratio [HR] = 8.30, p = 0.026) and criterion B (HR = 6.26, p = 0.009). CONCLUSIONS: AGV implantation in glaucoma eyes with high myopia showed lower surgical success compared to those without high myopia. Longer AL is a significant risk factor for surgical failure, underscoring the importance of careful monitoring after AGV implantation in such cases
Effects of oral nutritional supplements plus mature silkworm pill on cognitive function in Korean adults with mild cognitive impairment: a 12-week randomized blinded clinical trial
No full textOBJECTIVE: This study aimed to determine whether mature silkworm pills plus commercial oral nutritional supplements (ONS) could improve cognitive function, especially in individuals with mild cognitive impairment (MCI). METHODS: A total of 62 participants (70.6 +/- 8.5 years, 48.4% female), aged >/=50 years diagnosed with mild cognitive impairment but not dementia, were randomly assigned into the 12-week ONS plus silkworm pill group (30 participants, commercial ONS with mature silkworm pills) or the placebo group (32 participants, placebo ONS containing protein, carbohydrates, and fats, with placebo pills containing dextrin). During the 12-week intervention, participants consumed the allocated pills and ONS once daily. Additionally, nutritional education related to the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet therapy and proper eating habits was provided at weeks 0, 3, 6, and 9. The primary outcome was interval change in the Korean version of the Repeatable Battery for the Assessment of Neuropsychological Status (K-RBANS) after the 12-week intervention. Secondary outcomes included interval changes in nutrient intake, nutrition-related blood test results, nutritional quotient, and MIND score evaluation. RESULTS: After 12 weeks, the interval change in the delayed memory domain score of the K-RBANS was improved in the ONS plus silkworm pill group (65.9 +/- 19.0 vs. 70.5 +/- 19.0, p = 0.011), and there was also a difference between the intervention and control groups (p = 0.018). The interval changes in the total scale and other cognitive domain scores of the K-RBANS were not statistically significant. There were no significant differences in the pre- and post-comparison results between the placebo and ONS plus silkworm pill groups in terms of other secondary outcomes, including nutrition-related blood test results, nutritional quotient, and MIND score. CONCLUSION: After the 12-week intervention, the ONS and silkworm pill group showed a significant improvement in delayed memory compared with the placebo group. However, no significant differences were observed in other cognitive domains or secondary outcomes, such as nutrient intake, blood test results, nutrition quotient, or MIND score adherence. These findings suggest that, while the combination may have a positive impact on specific cognitive functions, further research is needed to fully understand its potential benefits and mechanisms of action. CLINICAL TRIAL REGISTRATION: https://trialsearch.who.int/Trial2.aspx?TrialID=KCT0007304
Anthropometric Changes and Risk of Visual Impairment in Patients with Newly Diagnosed Type 2 Diabetes Mellitus
No full textComparison of oncologic outcomes between completion hysterectomy and no completion hysterectomy in patients who achieved complete response and completed childbearing after fertility-sparing treatment for early-stage endometrial cancer: Gynecologic Oncology Research Investigators coLLaborAtion study (GORILLA-3001)
No full textOBJECTIVE: This study evaluated oncological outcomes of completion hysterectomy versus no completion hysterectomy in patients who completed childbearing after achieving complete response (CR) with fertility-sparing treatment (FST) for early-stage endometrial cancer (EC). METHODS: Multicenter data were retrospectively reviewed for patients with presumed stage IA, grade 1 endometrioid EC who gave birth after achieving CR with FST using progestin from 2005 to 2022. Oncologic outcomes were compared between patients who underwent completion hysterectomy and those who did not. RESULTS: Of 338 patients who achieved CR with FST, including those with second or third CR after relapses, 79 (52.7 %, 79/150) became pregnant (seven miscarriages, 72 live births). Completion hysterectomy was performed in 14 of 72 patients after delivery. During a median follow-up time of 61.0 months (range, 13-144) for the entire cohort, recurrence rates were 0 % (0/14) in the hysterectomy group and 22.4 % (13/58) in the non-hysterectomy group (P = 0.055). Progestin re-treatment was administered to 8 of 13 patients who relapsed, and CR was achieved in all. One patient, after a second live birth following re-treatment, was diagnosed with stage IVB extra-uterine disease during follow-up without completion hysterectomy. Five patients underwent hysterectomy immediately after recurrence, and none had extra-uterine disease. In multivariate analysis, recurrence before childbirth (HR 3.8, 95 % CI 1.0-13.3; p < 0.05) was significantly associated with recurrence after pregnancy. CONCLUSION: Completion hysterectomy is associated with improved oncologic outcomes in patients who deliver after FST. Therefore, hysterectomy should be considered for patients who have completed childbearing after FST
Development of a novel gene set, HepScope, and a CNN-based model for identifying malignant hepatocytes using multi-omics data
No full textMasterI. Introduction 1
II. Methodology 4
A. Data description 4
B. Processing of data 5
1. Processing of scRNA-seq data 5
2. Processing of stRNA-seq data 6
3. Processing of bulk RNA-seq data 6
4. Processing of proteomics data 6
C. Establishment of new gene set, HepScope 10
D. Known gene sets to identify HCC 10
E. single sample Gene Set Enrichment Analysis 11
F. Generation of 1D-CNN model based on HepScope expression matrices: HepScope-CNN 12
G. Benchmarking with alternative models 13
H. Performance evaluation 14
I. Tumor Immune Microenvironment analysis 15
J. Cell-cell interaction analysis 15
K. Differentially expressed protein analysis 15
L. Gene ontology and KEGG analysis 16
M. Protein-protein interaction analysis 16
III. Results 17
A. Lack of existing tools to identify malignant hepatocytes at the single-cell level 17
B. Development of novel biomarker discriminating malignant hepatocytes at the single cell level 19
C. Validation of capability of HepScope geneset in multi-omic data 25
D. Development of novel AI model, HepScope-CNN 27
E. Benchmarking of HepScope-CNN with other AI-based models 29
F. Investigation of tumor immune microenvironment in HCC using HepScope 32
G. Exploration of role of HepScope protein upregulated in HCC 36
IV. Discussion 44
References 4
NLRP3 인플라마좀 억제를 통한 Aiouea padiformis 추출물의 항염증 효과 연구
No full textMasterI. Introduction 1
II. Materials and Methods 5
1. Reagents and antibodies 5
2. Plant sample collection 6
3. In vitro study 6
3.1 Cell culture and stimulation 6
3.2 In vitro cell viability assay 7
3.3 NF-κB luciferase activity reporter gene assay 7
3.4 Measurement of cellular ROS assay 8
3.5 Measurement of mitochondrial membrane potential 8
3.6 Immunoprecipitation 8
3.7 Measurement ATPase activity of NLRP3 9
3.8 ASC oligomerization and ASC speck staining 9
4. Statistical analysis 10
III. Results 11
1. Screening and Identification of Aiouea padiformis as a Potent NLRP3 Inflammasome Inhibitor 11
2. Cell Viability Assessment Confirming Non-Cytotoxicity of AP 14
3. Inhibition of NLRP3-Mediated IL-1β and IL-18 Secretion by AP 15
4. Selective Inhibition of NLRP3 Inflammasome Activation by AP, Independent of AIM2 and NLRC4 17
5. Suppression of NLRP3 Inflammasome by AP without Effect on NF-κB Signaling 19
6. Reduction of NLRP3 Activation Independent of K+ Efflux, ROS, and Mitochondrial Instability by AP 21
7. AP-mediated Inhibition of NLRP3 Inflammasome Assembly by Impeding ATPase Activity 24
8. Suppression of NLRP3 Inflammasome Assembly by AP, Confirmed by Reduced ASC Oligomerization and Speck Formation 26
IV. Discussion 29
V. References 32
국문 초록 3