Comparison of partial and total cystectomy for colorectal cancer with histologically confirmed bladder invasion.

BACKGROUND: Although organs are preserved and quality of life is improved, insufficient evidence is available for the oncologic safety of partial cystectomy in patients with colorectal cancer with suspected bladder invasion. Therefore, we aimed to compare partial and total cystectomy outcomes in patients with pathologically confirmed or clinically suspected bladder invasion. METHODS: Patients with colorectal cancer with suspected bladder invasion who underwent R0 resection from 2000 to 2020 were evaluated. Long-term outcomes were determined in patients with histologically confirmed bladder invasion. RESULTS: Of the 151 consecutive patients, 96 (64.6%) had histologically confirmed bladder involvement, and 105 (69.5%) underwent partial cystectomy. Operative time, estimated blood loss, and reoperation rate in ≤30 days were significantly worse in the total cystectomy group than in the partial cystectomy group. The overall recurrence rate was significantly higher in the total cystectomy group than in the partial cystectomy group (39.1% vs 21.9%; P = .046). Five-year overall survival (75.8% vs 53.2%; P = .006) rates were higher in the partial cystectomy group than in the total cystectomy group; however, disease-free survival (60.8% vs 41.6%; P = .088) rates were similar in patients with suspected bladder invasion. In patients with histologically confirmed bladder invasion, 5-year overall survival rates (78.1% vs 52.1%; P = .017) were higher in the partial cystectomy group than in the total cystectomy group; however, disease-free survival rates (53.4% vs 41.2%; P = .220) did not differ significantly. CONCLUSION: R0 resection is associated with favorable long-term outcomes in patients with locally advanced colorectal cancer. If R0 resection is possible, partial cystectomy is considered safe.

A lipase from Lacticaseibacillus rhamnosus IDCC 3201 with thermostability and pH resistance for use as a detergent additive.

Lipases are important biocatalysts and ubiquitous in plants, animals, and microorganisms. The high growth rates of microorganisms with low production costs have enabled the wide application of microbial lipases in detergent, food, and cosmetic industries. Herein, a novel lipase from Lacticaseibacillus rhamnosus IDCC 3201 (Lac-Rh) was isolated and its activity analyzed under a range of reaction conditions to evaluate its potential industrial application. The isolated Lac-Rh showed a molecular weight of 24 kDa and a maximum activity of 3438.5 ± 1.8 U/mg protein at 60 °C and pH 8. Additionally, Lac-Rh retained activity in alkaline conditions and in 10% v/v concentrations of organic solvents, including glycerol and acetone. Interestingly, after pre-incubation in the presence of multiple commercial detergents, Lac-Rh maintained over 80% of its activity and the stains from cotton were successfully removed under a simulated laundry  setting. Overall, the purified lipase from L. rhamnosus IDCC 3201 has potential for use as a detergent in industrial applications. KEY POINTS: • A novel lipase (Lac-Rh) was isolated from Lacticaseibacillus rhamnosus IDCC 3201 • Purified Lac-Rh exhibited its highest activity at a temperature of 60 °C and a pH of 8, respectively • Lac-Rh remains stable in commercial laundry detergent and enhances washing performance.

Recent advances in earth-abundant transition metal-catalyzed dihydrosilylation of terminal alkynes.

Over the past few years, earth-abundant transition metal-catalyzed hydrosilylation has emerged as an ideal strategy for the synthesis of organosilanes. The success in this area of research has expanded to the advancements of alkyne dihydrosilylation reactions, offering broadened synthetic applications through the selective installation of two silyl groups. In particular, catalysts based on Fe, Co, and Ni have engendered enabling platforms for mild transformations with a range of distinct regioselectivity. This mini-review summarizes recent advances in this research field, highlighting the unique features of each system from both synthetic and mechanistic perspectives.

Nationwide Prevalence of Video Head Impulse Test Abnormality and its Risk Factors in South Korea.

OBJECTIVE: To identify the prevalence of and relevant information for video head impulse test (vHIT) abnormality in a large population. STUDY DESIGN: A cross-sectional design. SETTING: Korean National Health and Nutrition Examination Survey, 2021. METHODS: The sample was representative of the Korean population, with 2237 participants aged ≥40 years. A vHIT was performed to evaluate vestibular function. The vestibulo-ocular reflex (VOR) gain and the presence of reproducible catch-up saccades was assessed in a vHIT. Participants also completed questionnaires for demographics, socioeconomic status, and basic information regarding systemic diseases and dizziness and underwent hearing tests with automated pure-tone audiometry. RESULTS: The prevalence of vHIT abnormality was 22.5%, with unilateral (14.3%) being more common than bilateral (8.2%). The prevalence of vHIT abnormality increased significantly with age, with the highest rate observed in individuals aged >70 years (42.5%). Both hearing and VOR gain deteriorated with age, but the patterns of age-related progression were different. While hearing loss (HL) deteriorated gradually and progressively throughout adulthood, VOR gain deterioration was markedly evident after 70 years of age. CONCLUSION: Considering the high prevalence of vHIT abnormality, appropriate social and medical policies are needed to prevent associated injuries and improve patients' quality of life. The distinct age-related changes in HL and objective findings of vestibular dysfunction indicate the need for different approaches to address these social problems in aging countries.

Effect duration of lumbar sympathetic ganglion neurolysis in patients with complex regional pain syndrome: a prospective observational study.

Lumbar sympathetic ganglion neurolysis (LSGN) has been used for long-term pain relief in patients with complex regional pain syndrome (CRPS). However, the actual effect duration of LSGN has not been accurately measured. This prospective observational study measured the effect duration of LSGN in CRPS patients and investigated the relationship between temperature change and pain relief. After performing LSGN, the skin temperatures of both the maximum pain site and the plantar area in the affected and unaffected limbs were measured by infrared thermography, and pain intensity was assessed before and at 2 weeks, 1 month, and 3 months. The median time to return to baseline temperature was calculated using survival analysis. The skin temperature increased significantly at all-time points relative to baseline in both regions (maximum pain site: 1.4 °C ± 1.0 °C, plantar region: 1.28 °C ± 0.8 °C, all P < 0.001). The median time to return to baseline temperature was 12 weeks (95% confidence interval [CI] 7.7-16.3) at the maximum pain site and 12 weeks (95% CI 9.4-14.6) at the plantar area. Pain intensity decreased significantly relative to baseline, at all-time points after LSGN. In conclusion, the median duration of the LSGN is estimated to be 12 weeks.

Lesion-aware cross-phase attention network for renal tumor subtype classification on multi-phase CT scans.

Multi-phase computed tomography (CT) has been widely used for the preoperative diagnosis of kidney cancer due to its non-invasive nature and ability to characterize renal lesions. However, since enhancement patterns of renal lesions across CT phases are different even for the same lesion type, the visual assessment by radiologists suffers from inter-observer variability in clinical practice. Although deep learning-based approaches have been recently explored for differential diagnosis of kidney cancer, they do not explicitly model the relationships between CT phases in the network design, limiting the diagnostic performance. In this paper, we propose a novel lesion-aware cross-phase attention network (LACPANet) that can effectively capture temporal dependencies of renal lesions across CT phases to accurately classify the lesions into five major pathological subtypes from time-series multi-phase CT images. We introduce a 3D inter-phase lesion-aware attention mechanism to learn effective 3D lesion features that are used to estimate attention weights describing the inter-phase relations of the enhancement patterns. We also present a multi-scale attention scheme to capture and aggregate temporal patterns of lesion features at different spatial scales for further improvement. Extensive experiments on multi-phase CT scans of kidney cancer patients from the collected dataset demonstrate that our LACPANet outperforms state-of-the-art approaches in diagnostic accuracy.

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Pleural metastasis is the most common cause of malignant diseases involving the pleura, and characterized by pleural effusion, nodules, and thickening. Pleuroparenchymal fibroelastosis (PPFE) is a disease characterized by apical pleural thickening and subjacent parenchymal fibrosis. We report a case of a 60-year-old male with lung cancer in the left lower lobe and underlying PPFE combined with left apical pleural metastasis. Initially, asymmetric left apical pleural thickening due to pleural metastasis was mistaken for PPFE. Additionally, we describe the imaging and histopathological findings of PPFE, including MRI findings.

Effects of temperature, pH, and relative humidity on the growth of Penicillium paneum OM1 isolated from pears and its patulin production.

Patulin is a mycotoxin produced by several species of Penicillium sp., Aspergillus sp., and Byssochlamys sp. on apples and pears. Most studies have been focused on Penicillium expansum, a common postharvest pathogen, but little is known about the characteristics of Penicillium paneum. In the present study, we evaluated the effects of temperature, pH, and relative humidity (RH) on the growth of P. paneum OM1, which was isolated from pears, and its patulin production. The fungal strain showed the highest growth rate at 25 °C and pH 4.5 on pear puree agar medium (PPAM) under 97 % RH, while it produced the highest amount of patulin at 20 °C and pH 4.5 on PPAM under 97 % RH. Moreover, RT-qPCR analysis of relative expression levels of 5 patulin biosynthetic genes (patA, patE, patK, patL, and patN) in P. paneum OM1 exhibited that the expression of the 4 patulin biosynthetic genes except patL was up-regulated in YES medium (patulin conducive), while it was not in PDB medium (patulin non-conducive). Our data demonstrated that the 3 major environmental parameters had significant impact on the growth of P. paneum OM1 and its patulin production. These results could be exploited to prevent patulin contamination by P. paneum OM1 during pear storage.

Discovery and Validation of Survival-Specific Genes in Papillary Renal Cell Carcinoma Using a Customized Next-Generation Sequencing Gene Panel.

PURPOSE: Papillary renal cell carcinoma (PRCC), the second most common kidney cancer, is morphologically, genetically, and molecularly heterogeneous with diverse clinical manifestations. Genetic variations of PRCC and their association with survival are not yet well-understood. This study aimed to identify and validate survival-specific genes in PRCC and explore their clinical utility. MATERIALS AND METHODS: Using machine learning, 293 patients from the Cancer Genome Atlas-Kidney Renal Papillary Cell Carcinoma (TCGA-KIRP) database were analyzed to derive genes associated with survival. To validate these genes, DNAs were extracted from the tissues of 60 Korean PRCC patients. Next generation sequencing was conducted using a customized PRCC gene panel of 202 genes, including 171 survival-specific genes. Kaplan-Meier and Log-rank tests were used for survival analysis. Fisher's exact test was performed to assess the clinical utility of variant genes. RESULTS: A total of 40 survival-specific genes were identified in the TCGA-KIRP database through machine learning and statistical analysis. Of them, 10 (BAP1, BRAF, CFDP1, EGFR, ITM2B, JAK1, NODAL, PCSK2, SPATA13, and SYT5) were validated in the Korean-KIRP database. Among these survival gene signatures, three genes (BAP1, PCSK2, and SPATA13) showed survival specificity in both overall survival (OS) (p = 0.00004, p = 1.38 × 10-7, and p = 0.026, respectively) and disease-free survival (DFS) (p = 0.00002, p = 1.21 × 10-7, and p = 0.036, respectively). Notably, the PCSK2 mutation demonstrated survival specificity uniquely in both the TCGA-KIRP (OS: p = 0.010 and DFS: p = 0.301) and Korean-KIRP (OS: p = 1.38 × 10-7 and DFS: p = 1.21 × 10-7) databases. CONCLUSIONS: We discovered and verified genes specific for the survival of PRCC patients in the TCGA-KIRP and Korean-KIRP databases. The survival gene signature, including PCSK2 commonly obtained from the 40 gene signature of TCGA and the 10 gene signature of the Korean database, is expected to provide insight into predicting the survival of PRCC patients and developing new treatment.

Taguchi Optimization of Wetting, Thermal and Mechanical Properties of Sn-1.0wt.%Ag-0.5wt.%Cu Alloys Modified with Bi and Sb.

This study was conducted on SAC105 (Sn-1wt.%Ag-0.5wt.%Cu) lead-free solder modified with Bi and Sb. The wetting, melting point, and mechanical properties were analysed with the addition of 1~5 wt.%Bi and 1~5 wt.%Sb for SAC105 base alloy. The wetting characteristics were assessed by wetting time (zero cross time, ZCT) obtained from wetting balance tests. The mechanical properties were analysed by tensile tests. Considering two factors (Bi, Sb), a three-level (0, 1, 2 wt.%) design of experiment (DOE) method array was applied for Taguchi optimization. The results indicated that the solder wetting increased as Bi content increased, while it decreased with Sb. The ZCT decreased with increasing Bi content up to 4 wt.%, while it increased proportionally to Sb content. The melting point, measured using a differential scanning calorimeter (DSC), showed that the melting point tended to decrease according to Bi increase, while it increases depending on the Sb content. Increase in Bi and Sb levels resulted in enhanced tensile strength in the mechanical properties tests, with Bi having a more noticeable impact. The Taguchi optimized conditions for the Bi and Sb studies were found to be 2 wt.%Bi and 2 wt.%Sb. This led to an optimal set of 0.9 s of wetting time, a 222.55 °C melting point, a 55 MPa tensile strength, and a 50% elongation.

Enhancing the Internet of Medical Things (IoMT) Security with Meta-Learning: A Performance-Driven Approach for Ensemble Intrusion Detection Systems.

This paper investigates the application of ensemble learning techniques, specifically meta-learning, in intrusion detection systems (IDS) for the Internet of Medical Things (IoMT). It underscores the existing challenges posed by the heterogeneous and dynamic nature of IoMT environments, which necessitate adaptive, robust security solutions. By harnessing meta-learning alongside various ensemble strategies such as stacking and bagging, the paper aims to refine IDS mechanisms to effectively counter evolving cyber threats. The study proposes a performance-driven weighted meta-learning technique for dynamic assignment of voting weights to classifiers based on accuracy, loss, and confidence levels. This approach significantly enhances the intrusion detection capabilities for the IoMT by dynamically optimizing ensemble IDS models. Extensive experiments demonstrate the proposed model's superior performance in terms of accuracy, detection rate, F1 score, and false positive rate compared to existing models, particularly when analyzing various sizes of input features. The findings highlight the potential of integrating meta-learning in ensemble-based IDS to enhance the security and integrity of IoMT networks, suggesting avenues for future research to further advance IDS performance in protecting sensitive medical data and IoT infrastructures.

Enzymatically Oxidized Carbohydrates As Dicarbonyl Biobased Cross-Linkers for Polyamines.

Carbonyl cross-linkers are used to modify textiles and form resins, and are produced annually in megatonne volumes. Due to their toxicity toward the environment and human health, however, less harmful biobased alternatives are needed. This study introduces carbonyl groups to lactose and galactose using galactose oxidase from Fusarium graminearum (FgrGalOx) and pyranose dehydrogenase from Agaricus bisporus (AbPDH1) to produce four cross-linkers. Differential scanning calorimetry was used to compare cross-linker reactivity, most notably resulting in a 34 °C decrease in reaction peak temperature (72 °C) for FgrGalOx-oxidized galactose compared to unmodified galactose. Attenuated total reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS), and proton nuclear magnetic resonance (1H NMR) spectroscopy were used to verify imine formation and amine and aldehyde depletion. Cross-linkers were shown to form gels when mixed with polyallylamine, with FgrGalOx-oxidized lactose forming gels more effectively than all other cross-linkers, including glutaraldehyde. Further development of carbohydrate cross-linker technologies could lead to their adoption in various applications, including in adhesives, resins, and textiles.

A survey of current practices in post-polypectomy surveillance in Korea.

BACKGROUND/AIMS: We investigated the clinical practice patterns of post-polypectomy colonoscopic surveillance among Korean endoscopists. METHODS: In a web-based survey conducted between September and November 2021, participants were asked about their preferred surveillance intervals and the patient age at which surveillance was discontinued. Adherence to the recent guidelines of the U.S. Multi-Society Task Force on Colorectal Cancer (USMSTF) was also analyzed. RESULTS: In total, 196 endoscopists completed the survey. The most preferred first surveillance intervals were: a 5-year interval after the removal of 1-2 tubular adenomas < 10 mm; a 3-year interval after the removal of 3-10 tubular adenomas < 10 mm, adenomas ≥ 10 mm, tubulovillous or villous adenomas, ≤ 20 hyperplastic polyps < 10 mm, 1-4 sessile serrated lesions (SSLs) < 10 mm, hyperplastic polyps or SSLs ≥ 10 mm, and traditional serrated adenomas; and a 1-year interval after the removal of adenomas with highgrade dysplasia, >10 adenomas, 5-10 SSLs, and SSLs with dysplasia. In piecemeal resections of large polyps ( > 20 mm), surveillance colonoscopy was mostly preferred after 1 year for adenomas and 6 months for SSLs. The mean USMSTF guideline adherence rate was 30.7%. The largest proportion of respondents (40.8%-55.1%) discontinued the surveillance at the patient age of 80-84 years. CONCLUSIONS: A significant discrepancy was observed between the preferred post-polypectomy surveillance intervals and recent international guidelines. Individualized measures are required to increase adherence to the guidelines.

The Da Vinci Single-Port (SP) Treatment of Nutcracker Syndrome: A Case Report of a Novel Approach.

Nutcracker syndrome (NCS) is a rare disease affecting the left kidney. Surgical management is the only choice of treatment. Minimal invasive surgeries can be effective and may prevent complications of the major surgery. We present the case of a 33-year-old woman suffering from chronic left flank pain, diagnosed with NCS and treated with extravascular stents. Robotic-assisted extravascular stent insertion was performed using the Da Vinci single-port (SP) (Intuitive Surgical, Inc., Sunnyvale, USA) system. This approach offers the advantages of minimal invasiveness, precise stent placement, and reduced operative time. To our knowledge, this is the first case of using Da Vinci SP for this indication. Further studies are needed to evaluate the long-term outcomes and safety.

Association between traditional Korean fermented vegetables (kimchi) intake and serum lipid profile: using the Korean Genome and Epidemiology Study (KoGES) cohort.

PURPOSE: Dyslipidemia is a major health issue worldwide. There is growing interest in understanding the potential role of kimchi consumption on serum lipid profiles. However, there are limited epidemiological studies available on this topic. Therefore, this study aims to investigate the association between kimchi intake and serum lipid profiles. METHODS: We conducted an epidemiological study on participants (aged 40-69 years old) selected from the Health Examinees (HEXA) cohort study (n = 61,761). Four types of kimchi, including Baechu kimchi (cabbage kimchi), Kkakdugi (radish kimchi), Nabak kimchi/Dongchimi (a type of water kimchi made with fermented vegetables), and other kimchi, were assessed by a 106-food item semi-quantitative validated food frequency questionnaire (FFQ). Each kimchi intake is the average value calculated from the FFQ of the baseline and follow-up surveys. Fasting blood data were obtained at baseline and follow-up visits. Linear regression was used to examine the relationship between the intake of kimchi and the change in serum lipid profiles. RESULTS: The mean years between the baseline survey and a follow-up survey was 4.97 years. In this study, compared to the lowest category (< 1 serving/day), Baechu kimchi intake (2- < 3 servings/day) had more negative correlations with the change in values of total cholesterol (ß: -1.600, 95% confidence interval [CI, -2.744, -0.456]), triglycerides (ß: -3.372, 95% CI [-5.414, -1.330]), and low-density lipoprotein cholesterol (ß: -1.155, 95% CI [-2.214, -0.095]) in women. In men, Baechu kimchi intake (2- < 3 servings/day) had a more positive correlation associated with the changes in values of high-density lipoprotein cholesterol (ß: 0.049, 95% CI [0.031, 0.907]) compared to the lowest intake category (< 1 serving/day). CONCLUSIONS: Among Korean adults, consumption of kimchi, particularly Baechu kimchi, was found to be associated with improvements in serum lipid profiles. Further studies are required to conduct additional interventions to confirm the association between kimchi and serum lipid profiles.

Ticagrelor monotherapy for acute coronary syndrome: an individual patient data meta-analysis of TICO and T-PASS trials.

BACKGROUND AND AIMS: In patients with acute coronary syndrome (ACS), dual antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor is recommended for 12 months after drug-eluting stent (DES) implantation. Monotherapy with a potent P2Y12 inhibitor after short-term DAPT is an attractive option to better balance the risks of ischaemia and bleeding. Therefore, this study evaluated the efficacy and safety of ticagrelor monotherapy after short-term DAPT, especially in patients with ACS. METHODS: Electronic databases were searched from inception to 11 November 2023, and for the primary analysis, individual patient data were pooled from the relevant randomized clinical trials comparing ticagrelor monotherapy after short-term (≤3 months) DAPT with ticagrelor-based 12-month DAPT, exclusively in ACS patients undergoing DES implantation. The co-primary endpoints were ischaemic endpoint (composite of all-cause death, myocardial infarction, or stroke) and bleeding endpoint [Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding] at 1 year. RESULTS: Individual patient data from two randomized clinical trials including 5906 ACS patients were analysed. At 1 year, the primary ischaemic endpoint did not differ between the ticagrelor monotherapy and ticagrelor-based DAPT groups [1.9% vs. 2.5%; adjusted hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.56-1.13; P = .194]. The incidence of the primary bleeding endpoint was lower in the ticagrelor monotherapy group (2.4% vs. 4.5%; adjusted HR 0.54; 95% CI 0.40-0.72; P < .001). The results were consistent in a secondary aggregate data meta-analysis including the ACS subgroup of additional randomized clinical trials which enrolled patients with ACS as well as chronic coronary syndrome. CONCLUSIONS: In ACS patients undergoing DES implantation, ticagrelor monotherapy after short-term DAPT was associated with less major bleeding without a concomitant increase in ischaemic events compared with ticagrelor-based 12-month DAPT. STUDY REGISTRATION: PROSPERO (ID: CRD42023476470).

The changes in biethnic acceptance across daily settings and biethnic adolescents' psychological well-being during middle school transition.

INTRODUCTION: Patterns of biethnic adolescents' perceived biethnic acceptance across families, peers, and school contexts were examined during the transition from elementary to middle school in South Korea. We also examined how the transition patterns were related to their psychological outcomes during this period. METHODS: Utilizing 2-wave data (2017 and 2019) from the Panel Survey of Korean Multicultural Youth Adjustment, a latent transition analysis was conducted. Participants were biethnic adolescents who were in 5th or 6th grade at Wave 1 (N = 245; 51.02% female; Mage = 11.38). Their fathers were Korean, and mothers were immigrants from neighboring countries. Familial ethnic socialization, peer discrimination, and school multicultural climate scores were used as indicators of biethnic acceptance. Outcomes of self-esteem, depression, and biethnic affirmation were also examined. RESULTS: Latent profile and transition analyses yielded two groups (i.e., high acceptance and low acceptance) at each wave and four transition patterns (i.e., high-high, low-high, low-low, and high-low). Compared to high-high group, which was the most prevalent group, low-low and high-low groups reported lower self-esteem and ethnic affirmation, and greater depression at Wave 3. CONCLUSIONS: While for the majority of participants, their daily settings continued to be high in biethnic acceptance across the transition period, most at risk were those who perceived a decrease in biethnic acceptance in their daily settings. Results shed light on the need for support to maintain the context of high biethnic acceptance surrounding biethnic adolescents for their psychological well-being in school transitions.

Association Between Intracochlear Electrode Design and Electrically-Evoked Compound Action Potential Measures in Cochlear Implant Users.

OBJECTIVE: Cochlear implant (CI) electrode design has changed over time. Changes in intracochlear electrode design might influence the spread of neural activation along the auditory nerve and the number of independent channels. This study aimed to investigate the impact of intracochlear electrode design on the electrode-neuron interface using electrophysiological measures. STUDY DESIGN: Prospective cohort study. SETTING: A single tertiary hospital. METHODS: Fifty-two ears who were implanted with CI divided into 3 groups based on the design of intracochlear electrode arrays. Twenty-three ears were implanted with lateral wall straight electrodes. Eighteen ears were implanted with the slim perimodiolar electrode, and 11 ears were implanted with the old perimodiolar electrode. Various electrically-evoked compound action potential (ECAP) metrics were measured to quantify spread of excitation and channel interaction. RESULTS: ECAP threshold and slope were not significantly different among groups. ECAP spread of excitation (SOE) half-width and channel interaction index (CII) were significantly larger in subjects implanted with the lateral wall straight electrodes, indicating a wider spread of excitation compared to those with perimodiolar electrodes. Electrode impedance was significantly lower in subjects implanted with perimodiolar electrodes than those with lateral wall electrodes. CONCLUSION: Perimodiolar electrode groups yielded significantly narrower SOE half-widths and smaller CII than the lateral wall straight electrode group. This may indicate that the electrode array that hugged the modiolus had less overlap in neural excitation between adjacent electrodes, resulting in reduced channel interaction and potentially better spectral resolution than the electrode array positioned more laterally.

Pharmacokinetics of a Fixed-Dose Combination Product of Amlodipine, Losartan, Ezetimibe, and Rosuvastatin and Its Comparison with Co-administration of Four Individual Components in Healthy Participants.

BACKGROUND AND OBJECTIVE: This study aimed to assess and compare the pharmacokinetics, safety, and tolerability of a fixed-dose combination product (FDCP) comprising four different drugs (two antihypertensive drugs, amlodipine and losartan, and two lipid-lowering agents, ezetimibe and rosuvastatin) with their separate tablets. METHODS: A total of 60 participants were enrolled in this open-label, randomized, single-dose crossover study. Each participant received a single dose of FDCP and individual tablets during each period, with a 14-day washout period between the periods. The pharmacokinetic parameters of amlodipine, losartan, EXP3174 (an active metabolite of losartan), rosuvastatin, free ezetimibe, and total ezetimibe were evaluated and compared. RESULTS: The pharmacokinetic profiles of amlodipine, losartan, rosuvastatin, and ezetimibe after administration of the individual products were similar to those of FDCP. The geometric mean ratios and 90% confidence intervals for maximum concentration (Cmax) and area under the curve (AUC) of FDCP to individual tablets were within 0.8-1.25 for all six analytes. No clinically relevant changes were observed in the vital signs or physical, biochemical, hematological, electrocardiographic, or urinalysis findings during the study, and no serious adverse events were reported. CONCLUSION: This study demonstrated that a newly developed FDCP containing amlodipine, losartan, ezetimibe, and rosuvastatin exhibited pharmacokinetic equivalence with the individual products and met the regulatory criteria. Both formulations were well tolerated. CLINICAL TRIAL REGISTRATION: This trial (NCT04322266) was retrospectively registered on 9 September 2019.