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AURA: Arthroscopic Ultrasound-Assisted All-Inside Repair of Lateral Ankle Ligament
No full textArthroscopic ultrasound-assisted all-inside repair of lateral ankle ligament is a minimally invasive procedure that addresses chronic lateral ankle instability. This technique uses ultrasound guidance to facilitate accurate anchor placement and precise suture positioning, potentially reducing the risk of iatrogenic injury and improving anatomical repair. The combination of arthroscopy and ultrasound is expected to be more accurate and safer. In addition, it enables simultaneous treatment of intra-articular pathologies. This study describes the surgical method and discusses its potential advantages in clinical practice
Dual role of p21 in regulating apoptosis and mitotic integrity in response to doxorubicin in colon cancer cells
No full textThis study explores the multifaceted role of p21 in mediating cellular responses to DNA-damaging agents, with a focus on doxorubicin treatment in HCT116 colon carcinoma cells. We investigated how different doses of doxorubicin affect cells with varied p21 and p53 statuses, revealing distinct roles for p21 depending on the drug dosage. At high doses (HD), p21 is more critical than p53 in mediating apoptosis, whereas at low doses (LD), p21 is essential for preventing mitotic defects and multinucleation. Notably, reintroducing p21 or pharmacologically inhibiting CDK1 reduced multinucleation. The absence of p21 upon LD doxorubicin exposure led to aberrant chromosome segregation, persistent DNA damage response (DDR) activation, and increased non-homologous end-joining (NHEJ) activity, resulting in unrepaired DNA accumulation and multinucleation. Additionally, mitotic defects in p21-deficient cells were associated with mislocalization of key mitotic regulators, Aurora B and mitotic kinesin-like protein 1 (MKLP1), exacerbating defective mitosis. In summary, p21 functions as a dual regulator in response to DNA damage, promoting apoptosis at HD and preventing mitotic failure at LD. These insights have significant implications for cancer therapy, highlighting the potential of targeting the p21 to enhance treatment efficacy
Urinary DNA Methylation Test for Bladder Cancer Diagnosis
No full textIMPORTANCE: An accurate noninvasive biomarker test is needed for the early diagnosis of bladder cancer. OBJECTIVE: To evaluate the performance of a urinary DNA methylation test (PENK methylation) and compare its diagnostic accuracy with that of the nuclear matrix protein 22 (NMP22) test or urine cytology test. DESIGN, SETTING, AND PARTICIPANTS: In this prospective multicenter study at 10 sites in the Republic of Korea, individuals 40 years and older with hematuria undergoing cystoscopy within 3 months between March 11, 2022, and May 30, 2024, participated. The study participants were evaluated for bladder cancer using a urinary DNA methylation test. EXPOSURE: Urinary DNA methylation test, NMP22 test, and urine cytology test. MAIN OUTCOMES AND MEASURES: The primary outcomes were the sensitivity and specificity of the urinary DNA methylation test for high-grade or invasive bladder cancer. Secondary objectives included the accuracy of the test for overall bladder cancer (all stages and grades) and the comparison of sensitivities and specificities for bladder cancer between the urinary DNA methylation test and the NMP22 test or urine cytology test. RESULTS: Among the 1099 participants, 614 (55.9%) were male; participants had a mean (SD) age of 65 (10) years. Of the 1099 participants, 219 and 176 participants had bladder cancer and high-grade or invasive bladder cancer, respectively. The urinary DNA methylation test had sensitivity and specificity for high-grade or invasive bladder cancer of 89.2% (95% CI, 84.6%-93.8%) and 87.8% (95% CI, 85.6%-89.9%), respectively. Sensitivity and specificity for overall bladder cancer were 78.1% (95% CI, 72.6%-83.6%) and 88.8% (95% CI, 86.7%-90.8%), respectively. The positive predictive value for high-grade or invasive bladder cancer was 61.3% (95% CI, 55.4%-67.3%), and the negative predictive value was 97.6% (95% CI, 96.6%-98.7%). In comparison with the NMP22 test or urine cytology test, the urinary DNA methylation test showed significantly superior sensitivity for high-grade or invasive bladder cancer and overall bladder cancer. CONCLUSIONS AND RELEVANCE: In this prospective multicenter study of individuals with hematuria, the urinary DNA methylation test showed 89% sensitivity for detecting high-grade or invasive bladder cancer, outperforming the NMP22 test or urine cytology test with high specificity. While this test had an excellent negative predictive value, its positive predictive value was suboptimal
Rituximab in systemic sclerosis-associated interstitial lung disease: A systematic review and meta-analysis
No full textBackground: Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is a prominent form of connective tissue disease-associated interstitial lung disease with high prevalence and poor prognosis. The therapeutic use of corticosteroids is often limited, and the efficacy of conventional treatment may be suboptimal in certain cases. This systematic review and meta-analysis assessed the clinical effects of rituximab in SSc-ILD compared to conventional treatments and investigated potential clinical benefits in patients with disease progression despite conventional therapy.
Methods: A comprehensive literature search was conducted in Ovid MEDLINE((R)), Cochrane Library, EMBASE, and KoreaMed databases to identify studies on rituximab in adult SSc-ILD patients. Comparative studies with complete trial results were included. The primary outcome was the effect of rituximab on disease progression, measured by the change in forced vital capacity (FVC) compared to conventional treatments.
Results: From 940 articles, six studies (two randomized, four non-randomized) were included for analysis. Standardized mean differences (SMD) were used in analyses due to the varied durations of the included studies. The meta-analysis demonstrated that rituximab reduced the FVC decline in patients with SSc-ILD compared to conventional treatment (SMD 0.65; 95% confidence interval, 0.08-1.22, P = .03), though no significant differences were found in lung diffusing capacity or modified Rodnan skin score. Rituximab showed a significantly lower incidence of leukopenia compared to cyclophosphamide (P = .02) and showed a non-significant trend toward fewer instances of pneumonia and urinary tract infections.
Conclusions: The meta-analysis revealed that rituximab may be clinically beneficial in SSc-ILD that progresses despite conventional treatment. Further research is necessary to validate the clinical benefits of rituximab in SSc-ILD
Enhanced alcohol metabolism and sleep quality with continuous positive airway pressure following alcohol consumption
No full textWe aimed to examine the effect of continuous positive airway pressure on sleep quality and alcohol metabolism after alcohol consumption. Men (n = 53) aged >/= 19 years with sleep disorders who regularly consumed an average of >/= 1.0 g of alcohol/kg of bodyweight, were free of serious diseases (including liver disorders), and underwent polysomnography and continuous positive airway pressure titration between January 2016 and July 2021 were included. Participants drank a high dose of a traditional Korean liquor at a rate of 1.0 g/kg of bodyweight for 1 h. The main outcome measures included polysomnography results and blood and breath ethanol and acetaldehyde concentrations after alcohol consumption before and after sleep. Statistical analyses were performed using R software, version 4.0.5 (R Foundation, Vienna, Austria). Continuous positive airway pressure enhanced sleep quality after alcohol consumption, with oxygen significantly improving the metabolism of acetaldehyde over that of ethanol. Breath and blood sample analyses and polysomnography results revealed that continuous positive airway pressure improved sleep quality by reducing apnea-hypopnea index by 27.32 +/- 24.87 (p < 0.001), increasing rapid eye movement sleep by 2.08 +/- 6.74% (p < 0.05), and enhancing acetaldehyde breakdown by 21.2% (p < 0.001), while its effect on ethanol breakdown (4-5%) was not statistically significant. Continuous positive airway pressure is recommended after alcohol consumption for individuals with sleep apnea to enhance sleep quality
Lipid-Lowering Effect and Safety of Ezetimibe and Atorvastatin 5 mg in Patients With Primary Hypercholesterolemia or Mixed Dyslipidemia: A Randomized, Double-Blind, Parallel, Multicenter, Phase 3 Clinical Trial
No full textOBJECTIVE: This study aimed to compare the lipid-lowering effect and safety of low-intensity atorvastatin (5 mg) plus ezetimibe (10 mg) combination therapy (A5E10) with monotherapy regimens-atorvastatin 5 mg [A5], ezetimibe 10 mg [E10], and atorvastatin 10 mg [A10])-in dyslipidemia patients. METHODS: A randomized, double-blind, placebo-controlled trial involving 252 dyslipidemia patients was conducted at 25 centers in South Korea (NCT05970679). Participants aged >/= 19 years were randomized into four groups: A5E10, A5, E10, and A10. The primary endpoint was the percentage change in low-density lipoprotein cholesterol (LDL-C) levels from baseline to 8 weeks. Secondary endpoints included changes in other lipid parameters, lipid ratios, LDL-C goal achievement rates and safety assessments. RESULTS: The mean age of the patients was 63 years, and 51.2% were male. The A5E10 group showed significantly greater LDL-C reduction (47.6%) compared with A5 (33.4%), E10 (19.4%), and A10 (40.1%) at 8 weeks (p < 0.0001). A5E10 also significantly reduced triglyceride, non-high-density lipoprotein cholesterol, and apolipoprotein B levels. In addition, a significant reduction in LDL-C levels was observed over the 4 weeks, with a 46.7% reduction in LDL-C levels after 4 weeks of A5E10 administration. No severe adverse events were observed in the A5E10 group. CONCLUSION: The combination of low-intensity atorvastatin and ezetimibe was more effective than moderate-intensity atorvastatin monotherapy in lowering LDL-C levels and improving other lipid parameters. It was well-tolerated and demonstrated rapid benefits within a month, offering a promising alternative for patients with low to moderate cardiovascular risk who do not achieve adequate control with statin monotherapy
KF-NIPT: K-mer and fetal fraction-based estimation of chromosomal anomaly from NIPT data
No full textBACKGROUND: Non-Invasive Prenatal Testing (NIPT) is a technique that allows pregnant women to screen for chromosomal abnormalities in their developing fetus without the need for invasive procedures like amniocentesis or chorionic villus sampling. However, current methods to detect anomaly from maternal cell-free DNAs (cfDNAs) that are based on the sequence read counts calculating z-scores face challenges with false positives and negatives. To address these challenges, we aimed to develop a novel NIPT algorithm named KF-NIPT, which is derived from the initials of k-mer and fetal fraction used in its development with the goal of significantly improving accuracy. RESULTS: We developed a KF-NIPT, a new algorithm that estimate chromosomal anomaly by calculating K-mer-based sequence depth and fetal fraction from the whole genome sequencing (WGS) data. Moreover, we implemented a modified preprocessing pipeline for the WGS data, correcting the biases of the genomic mapping quality and the GC contents. The performance of our method was evaluated using publicly available NIPT data. We could demonstrate that our method has better accuracy and sensitivity compared to those of the previous methods. CONCLUSIONS: We found that using k-mer and fetal fraction reduces errors in NIPT and have integrated this into a pipeline, showing that the traditional read count-based z-score method can be improved. KF-NIPT is implemented in the R and Python environment. The source code is available at https://github.com/eastbrain/KF-NIPT . KF-NIPT has been tested on Ubuntu Linux-64 server and Linux-64 on Windows using a WSL (Windows Subsystem for Linux)
Validation of the conceptual framework and intervention scope of oral function rehabilitation exercise
No full textOBJECTIVES: This study used a Delphi survey to define the concept of oral function rehabilitation exercise (OFRE) based on the International Classification of Functioning, Disability, and Health (ICF) and to categorise intervention domains for community-dwelling older adults. BACKGROUND: While numerous studies have been conducted to improve oral function through exercise interventions, the conceptual definition of oral exercise remains unclear and there is a lack of systematic categorisation of oral exercise intervention domains. METHODS: A preliminary model was developed based on the key findings of 19 papers selected from a prior systematic review. Its validity was confirmed through a Delphi survey conducted twice with eight expert panellists. Consensus was achieved by evaluating the validity of the OFRE conceptual framework, the accuracy of OFRE conceptual definitions, and intervention domains. RESULTS: Through expert consensus, an ICF-based OFRE conceptual framework was developed that includes 21 factors that affect the oral health status of the older adults. The OFRE intervention domain for improving the health status consisted of oral function rehabilitation warm-up exercise, masticatory function exercise, swallowing function exercise, articulatory function exercise, salivary function exercise, and oral function rehabilitation cool-down exercise, and 11 specific intervention methods were derived. CONCLUSIONS: The OFRE intervention can be used for planning and applying successful interventions to improve oral function and life function of older adults
Selection of cage height in oblique lateral interbody fusion: is a cage height larger than the adjacent level disc too much?
No full textPURPOSE: Distraction of the disc height using a large cage is essential for segmental reconstruction and indirect decompression in oblique lateral interbody fusion (OLIF). However, an oversized cage remains a risk factor for endplate injury and cage subsidence. The adjacent level disc height (AdDH) is a common anatomical reference for the original disc height at the index level. We aimed to evaluate whether a cage height (CH) larger than the AdDH is a risk factor for cage-related complications in OLIF. METHODS: This study involved a single-institution retrospective analysis of 176 consecutive patients who underwent one- or two- level OLIF. Each CH was categorized as group A (CH is larger than AdDH of > 2 mm), group B (CH is larger than AdDH of 0.05). CONCLUSION: Disc height distraction over the AdDH in OLIF was performed safely and effectively. Large cage insertion without cage-related complications is more dependent on the intraoperative distraction technique than on the preoperative conditions