In this paper we investigate serum lipoprotein(a), an independent risk factor for cardiovascular disease in the Korean pediatric population. Visiting local clinics and hospitals, 600 lipoprotein(a) ...tests were performed on 416 Korean children and adolescents (124 boys and 292 girls), with a median age of 11.1 years (interquartile range, IQR, 9.8–13.9). The median lipoprotein(a) level was 21.5 nmol/L (IQR, 8.2–51.7). Among the 416 patients, the 90th percentile value of the initial lipoprotein(a) measurement was 107.8 nmol/L. The proportion of patients with lipoprotein(a) ≥ 100 nmol/L was 11.3%. The lipoprotein(a) level and the proportion of patients with lipoprotein(a) ≥ 100 nmol/L were not significantly different among sex, or age group. Among the 416 patients, 122 (29.3%, 21 boys and 101 girls) underwent at least two follow-up lipoprotein(a) measurements. The median follow-up period was 6.7 months (IQR, 5.5–11.8). The median lipoprotein(a) level across the 122 patients was 25 nmol/L (IQR 10.0–72.0). Among those patients, seven (5.7%) experienced an increase in serum lipoprotein(a) to ≥100 nmol/L during follow-up measurements. Further studies are needed in the Korean pediatric population in order to clarify the clinical significance of this change long-term.
A precise oncologic approach for head and neck squamous cell carcinoma (HNSCC) is necessary. We performed a genomic profile-based umbrella trial for the patients with platinum-refractory recurrent ...and/or metastatic HNSCC.
In this multicenter, open-label, single-arm phase II trial, we performed targeted next-generation sequencing (NGS). Patients were assigned to each treatment arm on the basis of their matching genomic profiles: arm 1, alpelisib, a PIK3CA inhibitor; arm 2, poziotinib, an epidermal growth factor receptor/HER2 inhibitor; arm 3, nintedanib, an fibroblast growth factor receptor inhibitor; and arm 4, abemaciclib, a CDK4/6 inhibitor. If there was no matching target, patients were allocated to arm 5, duvalumab ± tremelimumab, anti-PD-L1/cytotoxic T-cell lymphocyte-4 inhibitor. When progressive disease (PD) occurred in arms 1-4, cross over to arm 5 was allowed. The primary end point was disease control rate (DCR) in arm 1 and overall response rate (ORR) in arms 2-5 by investigator assessment.
Between October 2017 and August 2020, 203 patients were enrolled, including crossover. In arm 1, the ORR was 21.2% and DCR was 65.6%. The ORR was 0% for arm 2, 42.9% for arm 3, 0% for arm 4, and 15.6% for arm 5. In the case of PD with durvalumab, tremelimumab was added, and the ORR for durvalumab + tremelimumab was 2.2%. The median progression-free survival was 3.4, 3.2, 5.6, 1.6, and 1.7 months for each arm, respectively. The median overall survival was 12.4, 6.1, 11.1, 9.1, and 12.7 months, respectively. Overall, the toxicity profiles were manageable, and there were no treatment-related deaths.
To our knowledge, this study is the first biomarker-driven umbrella trial for platinum-refractory HNSCC using matched molecular targeted agents. We found that NGS-based genomic phenotyping was methodologically feasible and applicable.
Small dense low-density cholesterol (sdLDL) has been the focus of studies due to its potential as an independent risk factor for atherosclerotic cardiovascular diseases. We aimed to investigate the ...utilization of sdLDL testing by LDL particle size analysis and the prevalence of an sdLDL predominant phenotype in Korean adult patients by visiting local clinics and hospitals. Among 9222 Korean adults (4577 men and 4645 women) with a median age of 62.8 years (interquartile range, IQR 54.5 to 71.8 years) undergoing lipid profile testing using LDL particle size analysis, the prevalence of hypercholesterolemia (total cholesterol ≥ 240 mg/dL), hypo HDL cholesterolemia (<40 mg/dL), and hyper LDL cholesterolemia (≥160 mg/dL) was 7.8%, 12.9%, and 0.5%, respectively. The overall prevalence of the sdLDL predominant non-A phenotype of LDL was 46.8% of study subjects. Approximately 32.8% of the study subjects possessed lipid test results that did not exhibit increased risk except for sdLDL (only the sdLDL predominant non-A phenotype as a risk factor). In Korea, sdLDL testing was utilized in patients whose LDL cholesterol level was not increased. Future studies to clarify the clinical significance of this test in the Korean population are needed.
•Macro geometry of a helical gear pair was optimized.•The objective functions used were gear mass, efficiency, and transmission error.•All three exhibited a trade-off relation in the optimal design ...space.•Five combinations were set to compare the optimal solution performance according to the combinations of the objective functions.•The optimization considering all three objectives showed better performance than the other combinations.
When designing helical gears, the goal is to optimize gear weight, efficiency, and noise while simultaneously achieving the required strength. In this study, the macro geometry of a helical gear pair was optimized for low weight, high efficiency, and low noise; further, trends of optimal solutions for five combinations of the three objectives were analyzed. The gear mass and efficiency were directly used as the design objectives. However, since the calculation of the gear noise is generally very complicated and time-consuming, the gear noise has not been directly used as the design objective, and the peak-to-peak static transmission error (PPSTE), which is the main source of the gear vibration, was selected as the design objective for the gear noise in the optimization. The objectives exhibited a trade-off relation between each other in the optimal space. If one of them was omitted, the objective considerably deteriorated. To analyze the results, the objectives were normalized and scored. As a result, most of the top ranks were from the optimal solutions considering the mass, efficiency, and PPSTE. Therefore, all three objectives should be considered in the gear optimization for low weight, high efficiency, and low noise.
Abstract Purpose The aim of this study was to evaluate the efficacy and tolerability of rosuvastatin/ezetimibe combination therapy in Korean patients with high cardiovascular risk. Methods This was a ...12-week, randomized, double-blind, placebo-controlled, multicenter study. A total of 337 patients were screened. After a 4-week run-in period, 245 of these patients with high or moderately high risk as defined by the National Cholesterol Education Program Adult Treatment Panel III guidelines were randomly assigned. Patients received 1 of 6 regimens for 8 weeks as follows: (1) rosuvastatin 5 mg, (2) rosuvastatin 5 mg/ezetimibe 10 mg, (3) rosuvastatin 10 mg, (4) rosuvastatin 10 mg/ezetimibe 10 mg, (5) rosuvastatin 20 mg, or (6) rosuvastatin 20 mg/ezetimibe 10 mg. The primary outcome variable was percentage change in the level of LDL-C at week 8 of drug treatment. Secondary outcome variables included percentage changes of other lipid variables and achievement rates of LDL-C targets. Tolerability analyses were also performed. Findings The percentage change of LDL-C ranged from –45% to –56% (mean, –51%) in the monotherapy groups and from –58% to –63% (mean, –60%) in the combination therapy groups. The percentage change was greater in the pooled combination therapy group than in the counterpart ( P < 0.001 for the pooled groups); this difference was more obvious for regimens with a lower statin dose. The percentage reductions of total cholesterol and triglycerides were greater in the combination groups than in the monotherapy groups. The LDL-C target achievement rates were 64% to 87% (mean, 73%) in the monotherapy groups and 87% to 95% (mean, 91%) in the combination groups ( P = 0.01 for the pooled groups). The rates were significantly greater in patients receiving the combination therapy than in the monotherapy at lower doses of rosuvastatin. The proportions of patients with various adverse events were not significantly different between the groups. Implications Rosuvastatin/ezetimibe combination therapy has better efficacy and target achievement rates than rosuvastatin monotherapy in patients with high cardiovascular risk.
Programmed cell death ligand 1 (PD-L1) is an immune checkpoint protein involved in immune evasion of malignant tumors. Confirmation of PD-L1 expression in non-small cell lung cancer (NSCLC) is ...necessary for the determination of immunotherapy using immune checkpoint inhibitors (ICIs). PDL-1 expression is currently analyzed by immunohistochemistry and is the only available biomarker that can guide the treatment of NSCLC using ICIs. The present study was conducted to compare the expression of three different commercial clones of PD-L1 in order for immunohistochemistry (IHC) for these clones to become more reliable for surgical pathologists.
This study examined the expression of PD-L1 in 76 cases of resected lung cancer using IHC. Three clones were examined: SP263, SP142, and 22C3PharmDx, which are commercially approved for quantifying PD-L1 expression in lung cancer.
Of the 76 patients whose samples were evaluated for PD-L1 using the IHC 22C3pharmDx assay, 19 (25.0%) had a tumor proportion score (TPS) of ≥50% and 41 (53.9%) had a PD-L1 TPS of ≥1%. Furthermore, using the SP263, 48.7% had a TPS of ≥1% and 18.4% of >50%. The SP142 assay was used to evaluate tumor cells (TCs) and immune cells (ICs). Twenty (26.3%) cases were positive for TCs and 25 (32.9%) were reactive for ICs.
These three commercial PD-L1 clones are comparable for detecting primary targets for anti-tumor immunotherapies. Careful evaluation by a pathologist is necessary to minimize misinterpretation errors.
This study compared the characteristics and mortality of new implantation of cardiac implantable electronic device (CIED) between tertiary and non-tertiary hospitals. From national health insurance ...claims data in Korea, 17,655 patients, who underwent first and new implantation of CIED between 2013 and 2017, were enrolled. Patients were categorized into the tertiary hospital group (n = 11,560) and non-tertiary hospital group (n = 6095). Clinical outcomes including in-hospital death and all-cause death were compared between the two groups using propensity-score matched analysis. Patients in non-tertiary hospitals were older and had more comorbidities than those in tertiary hospitals. The study population had a mean follow-up of 2.1 ± 1.2 years. In the propensity-score matched permanent pacemaker group (n = 5076 pairs), the incidence of in-hospital death (odds ratio OR: 0.76, 95% confidence interval CI: 0.43-1.32, p = 0.33) and all-cause death (hazard ratio HR: 0.92, 95% CI 0.81-1.05, p = 0.24) were not significantly different between tertiary and non-tertiary hospitals. These findings were consistently observed in the propensity-score matched implantable cardioverter-defibrillator group (n = 992 pairs, OR for in-hospital death: 1.76, 95% CI 0.51-6.02, p = 0.37; HR for all-cause death: 0.95, 95% CI 0.72-1.24, p = 0.70). In patients undergoing first and new implantation of CIED in Korea, mortality was not different between tertiary and non-tertiary hospitals.
The commonly unattended and hostile deployments of WSNs and their resource-constrained sensor devices have led to an increasing demand for secure energy-efficient protocols. Routing and data ...aggregation receive the most attention since they are among the daily network routines. With the awareness of such demand, we found that so far there has been no work that lays out a secure routing protocol as the foundation for a secure data aggregation protocol. We argue that the secure routing role would be rendered useless if the data aggregation scheme built on it is not secure. Conversely, the secure data aggregation protocol needs a secure underlying routing protocol as its foundation in order to be effectively optimal. As an attempt for the solution, we devise an energy-aware protocol based on LEACH and ESPDA that combines secure routing protocol and secure data aggregation protocol. We then evaluate its security effectiveness and its energy-efficiency aspects, knowing that there are always trade-off between both.
To develop an external vehicle for skin hydration and enhanced dermal drug delivery, a hydrogel-based ultra-moisturizing cream (HUMC) was successfully formulated with carbopol 934P, urea, Tinocare ...GL, grape seed oil, and other excipients. The HUMC showed plastic flow behavior due to a gel structure with a cream base. Different types of drug-free vehicles such as a hydrogel, conventional cream (CC), and three HUMCs were prepared and subjected to an in vivo skin hydration test on a hairless mouse using a corneometer. Hydration effect (∆AU) was in the order of HUMC2>HUMC1 ≥ CC>HUMC3>hydrogel. Using nile red (NR) and 5-carboxyfluorescein (5-CF) as lipophilic and hydrophilic fluorescent probes, respectively, in vitro skin permeation and accumulation studies were conducted using Franz diffusion cells. The values of steady-state flux (Jss, ng/h/cm2) were obtained: 74.8 (CC), 145.6 (HUMC1), and 161.9 (HUMC2) for NR delivery; 6.8 (CC), 8.3 (HUMC1), and 10.9 (HUMC2) for 5-CF delivery. The amounts retained in the skin at 12 h (Qr, ng/cm2) were determined: 86.4 (CC) and 102.0 (HUMC2) for NR; and 70.1 (CC) and 195.6 (HUMC2) for 5-CF. Confocal microscopy was used to visualize the distribution of the fluorescent probes. NR tended to be localized into the deeper part of the skin with adipose tissue whereas 5-CF localized in the upper layer of the skin. Thus we propose that HUMC2 is an efficacious vehicle for skin hydration and enhances dermal delivery of lipophilic and hydrophilic drugs.
Abstract Objectives This study sought to evaluate the optimal percutaneous coronary intervention techniques using drug-eluting stents for bifurcation coronary lesions. Background The optimal ...bifurcation stenting technique needs to be evaluated. Methods The trial included 2 randomization studies separated by the presence of side branch (SB) stenosis for patients having non–left main bifurcation lesions. For 306 patients without SB stenosis, the routine final kissing balloon or leave-alone approaches were compared. Another randomization study compared the crush or single-stent approaches for 419 patients with SB stenosis. Results Between the routine final kissing balloon and leave-alone groups for nondiseased SB lesions, angiographic restenosis occurred in 17.9% versus 9.3% (p = 0.064), comprising 15.1% versus 3.7% for the main branch (p = 0.004) and 2.8% versus 5.6% for the SB (p = 0.50) from 214 patients (69.9%) receiving 8-month angiographic follow-up. Incidence of major adverse cardiac events including death, myocardial infarction, or target vessel revascularization over 1 year was 14.0% versus 11.6% between the routine final kissing balloon and leave-alone groups (p = 0.57). In another randomization study for diseased SB lesions, 28.2% in the single-stent group received SB stents. From 300 patients (71.6%) receiving angiographic follow-up, between the crush and single-stent groups, angiographic restenosis rate was 8.4% versus 11.0% (p = 0.44), comprising 5.2% versus 4.8% for the main branch (p = 0.90) and 3.9% versus 8.3% for the SB (p = 0.12). One-year major adverse cardiac events rate between the crush and single-stent groups was 17.9% versus 18.5% (p = 0.84). Conclusions Angiographic and clinical outcomes were excellent after percutaneous coronary intervention using drug-eluting stents with any stent technique for non–left main bifurcation lesions once the procedure was performed successfully.
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