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Mortality Risk of Colistin vs. Non-Colistin Use in Cancer Patients with Multidrug-Resistant Gram-Negative Bacterial Infections: Stratified by Resistance Profile and Concomitant Medications
No full textBackground and Objectives: Cancer patients are particularly susceptible to infections caused by multidrug-resistant Gram-negative bacteria (MDR GNB) due to chemotherapy- or radiation therapy-induced immunosuppression. Colistin is often prescribed as a last-resort agent for MDR GNB infection, but its clinical benefit in oncology patients remains unclear. This study aims to evaluate the mortality risk associated with colistin versus non-colistin regimens in cancer patient with MDR GNB infections, stratified by resistance profiles, infection sites, and concomitant medication use. Materials and Methods: A retrospective cohort study was conducted in adult cancer patients with MDR GNB infections that are resistant to at least three antibiotic classes and identified from at least two anatomical sites at a tertiary care hospital in Korea. Propensity score-matched in a 1:3 ratio either to the colistin group or non-colistin group and multivariate Cox hazard regression analyses were used to evaluate mortality in cancer patients with MDR GNB infections, primarily Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Results: A total of 85 patients (29 patients in the colistin and 56 patients in the non-colistin group) were included in the analysis. Overall, colistin use did not show a statistically significant mortality benefit compared to non-colistin regimens (hazard ratio (HR) 0.93, 95% CI 0.47-1.87). However, the subgroup analysis revealed that colistin had a potential association with significantly lower mortality in pneumonia patients with aminoglycoside-resistant infections (HR 0.04, 95% CI 0.002-0.69). Concomitant use of antipsychotics and benzodiazepines in selected resistance profiles also correlated with improved outcomes. In contrast, a potential association was found between concomitant macrolide use and increased mortality in patients with fluoroquinolone- or penicillin-resistant profiles. Conclusions: Colistin may offer survival benefits in selected high-risk cancer patients with MDR GNB pneumonia. Treatment outcomes are influenced by resistance profiles, infection sites, and concomitant medications, indicating the significant importance of individualized antimicrobial therapy and antimicrobial stewardship in oncology patients
Real-World Effectiveness of Omalizumab Treatment in Adult Asthma Patients
No full textPURPOSE: Omalizumab improves clinical outcomes for patients with severe asthma (SA), but its long-term effectiveness and potential biomarkers for predicting patient response require further investigation. This study aimed to evaluate the real-world effectiveness of omalizumab in treating SA and to identify potential biomarkers for predicting a favorable treatment response. MATERIALS AND METHODS: Clinical outcomes were compared between asthma patients receiving omalizumab (omalizumab group) and those on inhaled corticosteroid with long-acting beta-agonist (ICS-LABA) alone (ICS-LABA group). Propensity score matching and Cox proportional hazards model were used to calculate hazard ratios (HRs). Study outcomes included severe asthma exacerbation (SAE), incompletely controlled asthma, intravenous (IV) corticosteroid use, and asthma-related hospitalization. Incompletely controlled asthma was defined by blood eosinophil counts >/=150 cells/microL, fractional exhaled nitric oxide (FeNO) >/=25 ppb, forced expiratory volume in one second (FEV1%) <80%, or SAE occurrence. RESULTS: The omalizumab group had significantly lower risks of SAE (HR 0.17, p=0.03), incompletely controlled asthma (HR 0.56, p=0.04), IV corticosteroid treatment (HR 0.38, p=0.02), and asthma-related hospitalization (HR 0.27, p=0.05). Blood eosinophil count stayed lower in the omalizumab group. FEV1% was higher with the omalizumab group, while blood neutrophil count, FeNO, and serum total IgE showed no differences. Furthermore, subgroup analysis showed patients with treatment-favorable response (>50% reduction in systemic corticosteroid dose) exhibited decreased blood neutrophil counts but increased FEV1% and serum total IgE levels compared with the treatment-unfavorable group. CONCLUSION: Omalizumab treatment effectively reduces SAE and improves lung function and asthma control. Blood neutrophil counts and serum total IgE may be potential biomarkers for predicting favorable responses to omalizumab treatment
Pneumococcal Vaccination in Korean Adults: 2025 Recommendations by the Korean Society of Infectious Diseases
No full textThe 20-valent pneumococcal conjugate vaccine (PCV20) was approved by the Korean Ministry of Food and Drug Safety in October 2024. Despite the ongoing national immunization programs that include pneumococcal conjugate vaccines for children and 23-valent pneumococcal polysaccharide vaccine (PPSV23) for adults, the burden of invasive pneumococcal disease and pneumococcal community-acquired pneumonia remains high among the elderly and high-risk adults. Serotypes 3 and 19A, both included in 13-valent pneumococcal conjugate vaccine (PCV13), continue to be the most prevalent serotypes, and infections caused by non-PCV13 serotypes have increased. Given the need to broaden serotype coverage and simplify vaccination strategies, the Korean Society of Infectious Diseases recommends either a single dose of PCV20 or sequential vaccination with 15-valent pneumococcal conjugate vaccine followed by PPSV23 for adults aged 65 years and older, and for high-risk adults aged 19-64 years. These recommendations are based on immunogenicity, safety, and cost-effectiveness data from recent clinical trials. Vaccine selection, dosing intervals, and schedules should be determined according to individual underlying medical conditions and previous vaccination history to optimize protection against pneumococcal disease in the adult population
Impact of Annual Dry Weight Changes on Mortality and Cardiovascular Outcomes in Patients Undergoing Haemodialysis
No full textBACKGROUND: While obesity confers a survival advantage, weight loss adversely affects the survival of patients undergoing haemodialysis. However, given the limited information regarding its long-term effects on mortality and cardiovascular events, the health benefits of weight gain remain uncertain, particularly in Asian patients undergoing haemodialysis. METHODS: In a prospective multicentre cohort of patients undergoing haemodialysis in South Korea, patients whose dry weight was recorded at baseline and after 1 year were analysed. Patients were stratified into five groups according to annual dry weight change: stable (-2.0% to 1.9%, n = 245), mild (2.0% to 6.9%, n = 92) and moderate (>/= 7.0%, n = 20) dry weight gain and mild (-5.0% to -2.1%, n = 91) and moderate (< -5.0%, n = 77) dry weight loss. The associations of annual dry weight change with physical function and health-related quality of life were examined using cross-sectional analysis. The impact of annual dry weight changes on all-cause mortality and a composite of major adverse cardiovascular events (MACEs), defined as myocardial infarction, unstable angina, ischaemic stroke and peripheral artery disease requiring revascularization, was assessed in a longitudinal cohort of 525 individuals. RESULTS: In cross-sectional analysis, patients with diminished physical ability had a higher frequency of dry weight fluctuations. In longitudinal analysis, the mean age of the study participants was 59.9 years, and 62.3% were men. During a median follow-up of 3.1 years, death and MACE occurred in 105 (20.0%) and 31 (5.9%) patients, respectively. The risk of all-cause mortality was higher in patients with moderate dry weight gain or loss than in those with stable dry weight (adjusted hazard ratio [aHR] for moderate weight gain, 2.22; 95% confidence interval [CI], 0.96-5.13; p = 0.06; and aHR for moderate weight loss, 1.78; 95% CI, 1.07-2.95; p = 0.03). The risk of MACE was significantly higher in patients with weight gain (including mild and moderate) than in those with a stable dry weight (aHR, 3.02; 95% CI, 1.32-6.88; p = 0.009). Specifically, the increased risk of all-cause mortality attributable to moderate dry weight gain was limited to patients with obesity, whereas that for moderate dry weight loss was limited to patients with a normal body mass index. CONCLUSION: Moderate weight gain and loss were differentially associated with lower survival among patients undergoing haemodialysis, with the former in patients with obesity and the latter in normal-weight patients. Particularly, dry weight gain increased the risk of cardiovascular events
Lung-protective ventilation strategy in acute respiratory distress syndrome: a critical reappraisal of current practice
No full textRecognition of ventilator-induced lung injury has led to the development of lung-protective ventilation strategies, significantly influencing the management of acute respiratory distress syndrome (ARDS). By the end of the 20th century, five randomized controlled trials had compared the survival benefits of low tidal volume (VT) ventilation with those of traditional high VT ventilation. Two studies demonstrated favourable outcomes, most notably the landmark ARDS Network trial, which established the widely recommended VT of 6 mL/kg predicted body weight. However, the universal application of a fixed VT has been controversial, with poor adherence in clinical practice. The two trials used a greater contrast in VTs (6 vs. 12 mL/kg) than did the others (7-11 mL/kg) and incorporated methodological extremes, including toleration of elevated airway pressures or encouragement of unnecessary increases. In addition, disparities in underlying aetiologies and ventilatory parameters, such as unbalanced positive end-expiratory pressure and respiratory rates, may have influenced the results. There is no conclusive evidence to support the superiority of 6 mL/kg over intermediate VTs (7-10 mL/kg). Many subsequent studies have suggested that VT requirements should be individualized on the basis of lung mechanics and physiological status. The benefits of the current recommendations may be limited by factors such as the severity of hypoxemia, lung compliance, dead-space fraction, and inaccuracies in formula-based lung volume estimation. The goal of mechanical ventilation in ARDS patients is supportive rather than curative; therefore, a moderate approach is recommended in clinical practice. Further studies are needed to establish an individualized, patient-centred approach that allows more flexible and moderate settings
Psychometric Evaluation of the Self-Efficacy for Appropriate Medication Use Scale-Korean in People With Diabetes
No full textPurposeThe purpose of the study was to examine the psychometric properties of the Korean version of the Self-Efficacy for Appropriate Medication Use Scale (SEAMS-K).MethodsA cross-sectional design was used with 130 adults with type 2 diabetes taking medications from an outpatient clinic at a university hospital in Korea. Structured questionnaires were used for psychometric evaluation. The SEAMS-K validity was examined using exploratory factor analysis, and reliability was assessed using Cronbach's alpha and intraclass correlation coefficient. The original 13-item SEAMS was forward-translated and back-translated to ensure the translation equivalence of the SEAMS-K.ResultsFactor analysis for structural validity identified 3 dimensions of the SEAMS-K, explaining 71.2% of the total variance. The SEAMS-K showed significant associations with refilling and taking medication (r = -.58, P < .001), depressive symptoms (r = -.27, P = .002), and diabetes self-efficacy (r = .38, P < .001), thus, validating the construct validity hypotheses. As evidence of known groups' validity, there was a significant association between the SEAMS-K score according to A1C level (P = .042). The intraclass correlation coefficient for test-retest reliability was .91, and the alpha for internal consistency reliability was .92.ConclusionsThese results suggest that the SEAMS-K may be used clinically to assess the self-efficacy of appropriate medication use among Korean patients with type 2 diabetes
The Transfusion Timing of Plasma and Red Blood Cells in a 1: 1Ratio Is Relatedwith Survival and Functional Outcomes in Multiple Trauma Patients with Severe Traumatic Brain Injury
No full textOBJECTIVE: High-ratio plasma transfusion is proposed as a strategy for treating polytrauma with severe traumatic brain injury (TBI). This study analyzed outcomes based on the ratio and timing of plasma transfusion. METHODS: The clinical characteristics and results were collected from March 2016 to December 2022. Subjects included patients with severe TBI and polytrauma who underwent massive transfusion (MT). Severe TBI was defined as head abbreviated injury score (AIS) >/=3, and MT was defined as packed red blood cells (pRBCs) >/=4 units in the first 4 hours and >/=10 units in the first 24 hours. The 4-hour ratios were assigned to the "early group," and the 24-hour ratios to the "catch-up group." Next, the ratio of each group was divided into ">/=1 : 1 (plasma >/= pRBC)" and "<1 : 1 (plasma < pRBC)" groups, respectively. RESULTS: In this study, 532 patients participated. Mortality rates between the 1 : 2 and 1 : 1.5 ratios did not differ statistically; however, a significant difference was noted only at the 1 : 1 ratio (p=0.006). In the early group, outcomes did not significantly differ. The logistic regression for 30-day mortality identified independent risk factors, including advanced age, low Glasgow coma scale (GOS) scores, high AIS head scores, and a ratio <1 : 1. For the catch-up group, the odds ratio for a favorable GOS at >/=1 : 1 was 1.61, with a 30-day mortality rate of 0.60 when comparing >/=1 : 1 to <1 : 1 ratios. CONCLUSION: This study showed that maintaining a >/=1 : 1 plasma ratio for 24 hours improved functional outcomes and survival, without increased morbidity. Therefore, high-ratio plasma transfusion may be effective in the treatment of patients with polytrauma and severe TBI
Distal Oblique Bundle and Membranous Thickening: Morphology and Integration with the Triangular Fibrocartilage Complex
No full textBackground: The distal oblique bundle (DOB) of the interosseous membrane (IOM) has been recognized as an important stabilizer of the distal radioulnar joint (DRUJ). However, its prevalence, morphology, and distal attachments-particularly its relationship to the articular disc and the extensor carpi ulnaris (ECU) tendon sheath-remain inconsistently described. Clarifying these anatomical details is essential for understanding DRUJ stability and guiding surgical reconstruction. Methods: The distal IOM was examined in 48 specimens from 24 embalmed Korean cadavers. In 46 dissected specimens, the presence, morphology, and attachment sites of distal interosseous structures were documented, and attachment levels were measured. In 38 specimens, attachment to the articular disc was assessed. In addition, serial transverse sections from one cadaver were analyzed to confirm three-dimensional relationships. Results: Two morphological patterns were identified: a distinct DOB (21/46, 45.7%) and, when absent, a membranous thickening of the distal IOM (25/46, 54.3%). The mean attachment level was 39.1 +/- 9.7 mm for the DOB and 25.4 +/- 4.8 mm for the membranous thickening. Both structures assumed an oblique orientation, fanning palmarly toward the capsule and articular disc and dorsally toward the ECU tendon sheath and dorsal septum. In 26 of 38 specimens (68.4%), these structures attached to the proximal palmar portion of the articular disc. Serial transverse sections confirmed this oblique configuration, linking palmar and dorsal stabilizers of the DRUJ. Conclusions: The distal IOM consistently forms specialized structures-either a DOB or a membranous thickening-that integrate with the triangular fibrocartilage complex. By bridging palmar and dorsal stabilizers, these structures contribute to joint congruency and load transfer during forearm rotation. A refined anatomical understanding of these patterns provides clinically relevant insights for surgical preservation or reconstruction, with the potential to improve outcomes in patients with chronic DRUJ instability
Effect of systemic inflammation on the repair of damaged brains.
No full textDoctorI. INTRODUCTION 1
A. Overview of the neuronal and non-neuronal cells in the injured brain 1
1. Neurons 1
2. Astrocytes 2
3. Microglia 4
4. Monocytes 5
B. Major events in the injured brain 6
1. Cell death 6
2. Clearance of dead cells/Phagocytosis 7
3. Repair and inflammation 8
C. Effect of systemic inflammation on injured brains 9
1. Effect of systemic inflammation on blood and brain cells 9
2. Systemic inflammation and brain injury 11
3. Systemic inflammation and repair of injured brain 12
D. Aims of the study 14
II. MATERIALS AND METHODS 16
1. Animals and LPS-ip injection 16
2. Stereotaxic injection 16
3. Magnetic Resonance Imaging (MRI) 17
4. Tissue Preparation 18
5. Immunostaining 18
6. Isolation of peritoneal macrophages and peripheral blood mononuclear cells (PBMCs) 19
7. Total protein extraction and Western blotting 20
8. Quantitative real-time polymerase chain reaction (QPCR) and Reverse Transcriptase PCR (RT-PCR) 21
9. RNA sequencing and data analysis 22
10. Statistical analysis 23
III. RESULTS 26
A. Systemic inflammation attenuates the repair of damaged brains through reduced phagocytic activity of monocytes infiltrating brain. 26
1. Transcriptomic analysis of injured brains of mice with and without systemic inflammation 27
2. LPS-ip reduces initial brain damage but delays removal of dead neurons and repair of injured brains. 33
3. Systemic inflammation increases monocytes infiltration with scattered distribution in the injured brain 39
4. Systemic inflammation decreases phagocytic efficiency of monocytes in the injured brain 47
B. Systemic inflammation decreases initial brain injury but attenuates neurite extension and synapse formation in injured brains 53
1. Systemic inflammation reduces initial brain injury and increases the expression of defense and anti-apoptosis genes 53
2. LPS-ip significantly altered gene expression related to the repair and attenuates neurites regeneration 60
3. LPS-ip attenuated synapse formation in the injured brain. 62
IV. DISCUSSION 71
A. Systemic inflammation attenuates the repair of damaged brains through reduced phagocytic activity of monocytes infiltrating brain. 71
B. Systemic inflammation decreases initial brain injury but attenuates neurite extension and synapse formation in injured brains. 74
V. SUMMARY AND CONCLUSION 79
REFERENCES 8
DNA 손상 반응 과정에서 53BP1의 상분리와 p53 매개 전사 활성 조절에서의 RSF1의 역할
No full textDoctorCHAPTER I : Introduction 1
A. DNA damage response (DDR) 1
B. Mechanisms of DNA double-strand break repair 2
C. P53-mediated transcriptional regulation in the DNA damage response 6
D. The chromatin remodeling function of RSF1 10
E. 53BP1 function in DNA repair and transcription 12
F. Phase separation in the DNA damage response 16
G. Aims of this study 20
CHAPER II : RSF1 coordinates p300 and FACT to regulate p53-dependent transcription 22
A. Chapter Introduction 23
B. Materials and Methods 25
1. Cell culture 25
2. Plasmid and RNA interference 25
3. Western blot analysis 26
4. Antibodies and reagents 26
5. Flow cytometric (FACS) analysis 28
6. Whole-cell extraction 28
7. Immunofluorescence microscopy 28
8. Pull-down assay 29
9. Immunoprecipitation assay 29
10. Real-time PCR analysis 30
11. Reporter gene activity measurement using luciferase assay 30
12. Chromatin immunoprecipitation (ChIP) assay 30
13. Statistical analysis 32
C. Results 33
1. RSF1 promotes p53-dependent transcription and cell cycle arrest in response to DNA damage 33
2. RSF1 controls p53 transcriptional activity by regulating its acetylation at lysine 382 37
3. RSF1 facilitates p53-dependent transcription by coordinating p300 activity and pre-initiation complex assembly 41
4. RSF1 enhances p21 transcription by bridging the FACT complex and RNA polymerase II to promoter regions 45
CHAPER III : RSF1 supports 53BP1 repair condensate formation through chromatin remodeling 49
A. Chapter Introduction 50
B. Materials and Methods 52
1. Cell culture 52
2. Cloning and plasmids 52
3. siRNA sequences, antibodies, and chemicals 53
4. OptoDroplet assay 55
5. Fluorescence recovery after photobleaching (FRAP) 56
6. Laser microirradiation and immunofluorescence 56
7. Immunoblotting 56
8. Recombinant Protein Expression and Purification from Sf9 Insect Cells and E. coli 57
9. Poly-ADP-ribosylation in vitro assay 57
10. Quantitative real-time PCR 58
11. Reporter gene activity measurement using luciferase assay 58
12. Chromatin immunoprecipitation (ChIP) assay 59
13. Image quantification 59
14. Statistical analysis 60
C. Results 61
1. RSF1 predominantly comprises intrinsically disordered regions (IDRs) 61
2. RSF1 alone does not form liquid condensates 65
3. RSF1 is required for the 53BP1-mediated liquid condensate formation 69
4. The C-terminal IDR3 of RSF1 is required for 53BP1 condensate formation 73
5. RSF1 modulates 53BP1 condensate formation through PARylation dynamics 77
6. RSF1 is required for 53BP1 condensate formation but does not affect FUS-driven condensates 81
7. RSF1 facilitates timely PARG recruitment to DNA damage sites, independent of PARP1 accumulation 84
8. Delayed PARG recruitment underlies 53BP1 condensate defects in RSF1 C1-expressing cells 87
9. Disruption of phase separation attenuates p53 target gene transcription following DNA damage 90
10. RSF1-mediated condensates promote p53 recruitment to chromatin and transcriptional activation 93
CHAPER IV : Discussion 96
REFERENCES 106
국문요약 12