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Rivaroxaban Once-Daily vs. Dose-Adjusted Vitamin K Antagonist on Biomarkers in Acute Decompensated Heart Failure and Atrial Fibrillation (ROAD HF-AF): Rationale and Design of an Investigator-Initiated Multicenter Randomized Prospective Open-Labeled Pilot Clinical Study.
Cho, I, Oh, J, Kim, IC, Chung, H, Lee, JH, Kim, HM, Byun, YS, Yoo, BS, Choi, EY, Chung, WJ, et al
Frontiers in cardiovascular medicine. 2021;:765081
Abstract
Background: Clinical trials of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with chronic heart failure and atrial fibrillation (AF) have demonstrated reduced risks of stroke and bleeding compared with vitamin K antagonists (VKAs). Here, we aim to assess the clinical efficacy and safety of rivaroxaban, a NOAC, compared with warfarin, a VKA, and the effects of rivaroxaban on cardiovascular biomarkers in patients with acute decompensated heart failure (ADHF) with reduced ejection fraction (≤40%) and AF. Methods: Rivaroxaban Once-daily vs. dose-adjusted vitamin K antagonist on biomarkers in Acute Decompensated Heart Failure and Atrial Fibrillation (ROAD HF-AF) is a randomized, open-labeled, controlled, prospective, multicenter pilot study designed to assess cardiovascular biomarkers and the safety of rivaroxaban (20 or 15 mg in patients with creatinine clearance 30-49 mL/min per day) compared with VKA (target international normalized range: 2-3) in 150 patients hospitalized with ADHF and AF. The primary endpoint is the change in circulating high-sensitivity cardiac troponin (hsTn) during hospitalization. The secondary endpoints are bleeding, hospital stay duration, in-hospital mortality, and changes in cardiovascular, renal, and thrombosis biomarkers. Patients will be followed for 180 days. Conclusion: We hypothesize that rivaroxaban will reduce myocardial injury and hemodynamic stress, as reflected by the biomarker status, within 72 h in patients with ADHF and AF, compared with VKA. We hope to facilitate future biomarker-based, large-scale outcome trials using NOACs in patients with ADHF and AF, based on the results of this multicenter, randomized, controlled study.
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Hydrogen-rich water reduces inflammatory responses and prevents apoptosis of peripheral blood cells in healthy adults: a randomized, double-blind, controlled trial.
Sim, M, Kim, CS, Shon, WJ, Lee, YK, Choi, EY, Shin, DM
Scientific reports. 2020;10(1):12130
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Oxidative stress indicates a state where excessive reactive oxygen species (ROS) overwhelm the biological antioxidant capacity, leading to disruption of ROS homeostasis and cellular damage. The aim of this study was to investigate the effects of hydrogen-rich water (HW) consumption in healthy adults through the extensive analyses of antioxidant capacity, peripheral blood mononuclear cell subsets and their transcriptome profile and to compare the effects of HW consumption with those of plain water (PW) consumption. This study is a 4-week, parallel-designed, randomized, double-blind, and placebo-controlled trial. The enrolled participants were randomly assigned to either the PW group (n=19) or the HW group (n=22). Results show that four-week consumption of HW induced a substantial increase in the antioxidant capacity and a decrease in oxidative stress of DNAs, although no significant results were found in the comparison of an intervention (HW) and the placebo (PW) group. Furthermore, the frequencies of apoptotic cells were significantly reduced by HW. Authors conclude that consumption of HW may promote biological antioxidant capacity for adults >30 years more than younger individuals.
Abstract
The evidence for the beneficial effects of drinking hydrogen-water (HW) is rare. We aimed to investigate the effects of HW consumption on oxidative stress and immune functions in healthy adults using systemic approaches of biochemical, cellular, and molecular nutrition. In a randomized, double-blind, placebo-controlled study, healthy adults (20-59 y) consumed either 1.5 L/d of HW (n = 20) or plain water (PW, n = 18) for 4 weeks. The changes from baseline to the 4th week in serum biological antioxidant potential (BAP), derivatives of reactive oxygen, and 8-Oxo-2'-deoxyguanosine did not differ between groups; however, in those aged ≥ 30 y, BAP increased greater in the HW group than the PW group. Apoptosis of peripheral blood mononuclear cells (PBMCs) was significantly less in the HW group. Flow cytometry analysis of CD4+, CD8+, CD20+, CD14+ and CD11b+ cells showed that the frequency of CD14+ cells decreased in the HW group. RNA-sequencing analysis of PBMCs demonstrated that the transcriptomes of the HW group were clearly distinguished from those of the PW group. Most notably, transcriptional networks of inflammatory responses and NF-κB signaling were significantly down-regulated in the HW group. These finding suggest HW increases antioxidant capacity thereby reducing inflammatory responses in healthy adults.
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Prognostic Factors for Severe Coronavirus Disease 2019 in Daegu, Korea.
Jang, JG, Hur, J, Choi, EY, Hong, KS, Lee, W, Ahn, JH
Journal of Korean medical science. 2020;(23):e209
Abstract
BACKGROUND Since its first detection in December 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 infection has spread rapidly around the world. Although there have been several studies investigating prognostic factors for severe COVID-19, there have been no such studies in Korea. METHODS We performed a retrospective observational study of 110 patients with confirmed COVID-19 hospitalized at a tertiary hospital in Daegu, Korea. Demographic, clinical, laboratory, and outcome data were collected and analyzed. Severe disease was defined as a composite outcome of acute respiratory distress syndrome, intensive care unit care, or death. RESULTS Diabetes mellitus (odds ratio [OR], 19.15; 95% confidence interval [CI], 1.90-193.42; P = 0.012), body temperature ≥ 37.8°C (OR, 10.91; 95% CI, 1.35-88.36; P = 0.025), peripheral oxygen saturation < 92% (OR, 33.31; 95% CI, 2.45-452.22; P = 0.008), and creatine kinase-MB (CK-MB) > 6.3 (OR, 56.84; 95% CI, 2.64-1,223.78, P = 0.010) at admission were associated with higher risk of severe COVID-19. The likelihood of development of severe COVID-19 increased with an increasing number of prognostic factors. CONCLUSION In conclusion, we found that diabetes mellitus, body temperature ≥ 37.8°C, peripheral oxygen saturation < 92%, and CK-MB > 6.3 are independent predictors of severe disease in hospitalized COVID-19 patients. Appropriate assessment of prognostic factors and close monitoring to provide the necessary interventions at the appropriate time in high-risk patients may reduce the case fatality rate of COVID-19.
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In vivo bone formation by human alveolar-bone-derived mesenchymal stem cells obtained during implant osteotomy using biphasic calcium phosphate ceramics or Bio-Oss as carriers.
Park, JC, Oh, SY, Lee, JS, Park, SY, Choi, EY, Cho, KS, Kim, CS
Journal of biomedical materials research. Part B, Applied biomaterials. 2016;(3):515-24
Abstract
OBJECTIVES The aim of this study was to evaluate HA coated with different ratios of TCP as a carrier for hABMSCs obtained during implant osteotomy in comparison to slowly-resorbing biomaterial, Bio-Oss, as a negative control, using in vitro and in vivo experiments. MATERIALS AND METHODS Human ABMSCs (hABMSCs) harvested during implant osteotomy were transplanted using HA/TCP or Bio-Oss as carriers in a murine ectopic transplantation model (n = 12). Pore size and cell affinity were evaluated in vitro. The area of newly formed bone was analyzed histometrically, the number of osteocytes was counted, and immunohistochemical staining was conducted against several markers of osteogenesis, including alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX-2), osteocalcin (OCN), and osteopontin (OPN). Osteoclast formation was evaluated by tartrate-resistant acid phosphatase staining. RESULTS The carrier materials had comparable pore sizes. The cell affinity assay resulted in a high proportion of cell adhesion (>90%) in all experimental groups. Substantial new bone and osteocyte formation was observed on both HA/TCP carriers, whereas it was minimal with Bio-Oss. Positive immunostaining for ALP, RUNX-2, OCN, and OPN was observed with HA/TCP, but only limited expression of osteogenic markers with Bio-Oss. Conversely, there was a minimal osteoclast presence with Bio-Oss, but a significant presence of osteoclasts with both HA/TCP carriers. CONCLUSIONS Both types of scaffolds, BCP and Bio-Oss, showed high stem cell-carrying potential, but the in vivo healing patterns of their complexes with hABMSC could be affected by the microenvironment on the surfaces of the scaffolds.
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Prevalence of chronic cough and possible causes in the general population based on the Korean National Health and Nutrition Examination Survey.
Koo, HK, Jeong, I, Lee, SW, Park, J, Kim, JH, Park, SY, Park, HY, Rhee, CK, Kim, YH, Jung, JY, et al
Medicine. 2016;(37):e4595
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Abstract
Although chronic cough is very common, its prevalence and causes have been rarely reported in the large general population including smokers. This study aimed to identify the prevalence of possible causes of chronic cough and their clinical impact.From Korean National Health and Nutrition Examination Survey (KNHANES) data including 119,280 adults aged over 40 years, 302 individuals with chronic cough were recruited irrespective of smoking status. Data from questionnaire, laboratory tests including spirometry, chest radiographs, and otorhinolaryngologic examination were analyzed.The prevalence of chronic cough in adults was 2.5% ± 0.2%. Current smokers occupied 47.7% ± 3.8% of study population and 46.8% ± 3.9% of the subjects showed upper airway cough syndrome (UACS). Based on spirometry, chronic obstructive pulmonary disease (COPD) was identified in 26.4% ± 3.5%. Asthma explained for 14.5% ± 2.8% of chronic cough. Only 4.1% ± 1.6% showed chronic laryngitis suggesting gastro-esophageal reflux-related cough. Abnormalities on chest radiography were found in 4.0% ± 1.2%. Interestingly, 50.3% ± 4.5% of study subjects had coexisting causes. In multivariate analysis, only current smoking (odds ratio [OR] 3.16, P < 0.001), UACS (OR 2.50, P < 0.001), COPD (OR 2.41, P < 0.001), asthma (OR 8.89, P < 0.001), and chest radiographic abnormalities (OR 2.74, P = 0.003) were independent risk factor for chronic cough. This pattern was not different according to smoking status excepting the prevalence of COPD.Smoking, COPD, and chest radiographic abnormalities should be considered as causes of chronic cough, along with UACS and asthma. Gastro-esophageal reflux-related cough is not prevalent in study population.
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Calorie intake of enteral nutrition and clinical outcomes in acutely critically ill patients: a meta-analysis of randomized controlled trials.
Choi, EY, Park, DA, Park, J
JPEN. Journal of parenteral and enteral nutrition. 2015;(3):291-300
Abstract
BACKGROUND The appropriate calorie intake to be provided to critically ill patients via enteral nutrition (EN) remains unclear. We performed a meta-analysis of randomized controlled trials to compare the effect of initial underfeeding and full feeding in acutely critically ill patients. MATERIALS AND METHODS We searched the Medline, EMBASE, and Cochrane Central Register of Controlled Trials databases to identify randomized controlled trials that compared underfeeding with full feeding in critically ill patients. The primary outcome was overall mortality. The secondary outcomes included length of hospital stay, length of intensive care unit (ICU) stay, duration of mechanical ventilation, incidence of pneumonia, Clostridium difficile colitis, other infectious complications, and gastrointestinal intolerance. RESULTS In total, 4 studies were included in this meta-analysis. There was no significant difference in overall mortality between the underfeeding and full-feeding groups (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.74-1.19; I (2) = 26.6%; P = .61). Subgroup analysis of the underfeeding subgroup that was fed ≥33.3% of the standard caloric requirement indicated that overall mortality was significantly lower in this underfeeding subgroup than in the full-feeding group (OR, 0.63; 95% CI, 0.40-1.00; I (2) = 0%; P = .05). In contrast, no difference in overall mortality was noted between the underfeeding subgroup that was fed <33.3% of the standard caloric requirement and the full-feeding group. The length of hospital stay and length of ICU stay did not differ between the 2 groups. Moreover, no differences in other secondary clinical outcomes were noted. CONCLUSIONS None of the analyzed clinical outcomes for the acutely critically ill patients were significantly influenced by the calorie intake of the initial EN.
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Relationship between serum vitamin D concentrations and clinical outcome of community-acquired pneumonia.
Kim, HJ, Jang, JG, Hong, KS, Park, JK, Choi, EY
The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease. 2015;(6):729-34
Abstract
SETTING Hospitalised patients with community-acquired pneumonia (CAP) in a tertiary referral hospital in South Korea. OBJECTIVE To determine the burden of vitamin D deficiency in patients hospitalised with CAP and to investigate whether vitamin D deficiency affected clinical outcomes. DESIGN Serum 25-hydroxyvitamin D (25[OH]D) levels were measured at admission; vitamin D deficiency was defined as 25(OH)D <20 ng/ml. Data were retrospectively analysed for incidence of vitamin D deficiency. The primary outcome was the relationship between serum vitamin D concentration and 28-day all-cause mortality in CAP. RESULTS The mean age was 68.1 years (standard deviation [SD] ± 14.6), and the mean pneumonia severity index was 98.0 (± SD 28.6). Of the 797 patients (males 66.0%), 641 (80.4%) had vitamin D deficiency. Overall mean serum 25(OH)D level was 14.0 ± 7.4 ng/ml. The 28-day all-cause mortality rate in vitamin D-deficient patients was significantly higher than in non-deficient patients (8.3% vs. 2.6%, P = 0.01), and serum vitamin D level was negatively associated with risk of 28-day mortality in CAP after adjustment for pneumonia severity index and serum lactate levels (OR 0.94, 95%CI 0.90-0.99, P < 0.01). CONCLUSION The prevalence of vitamin D deficiency was ~80% in patients hospitalised with CAP. Vitamin D deficiency was also a significant predictor of increased 28-day all-cause mortality.
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Effect of onion peel extract on endothelial function and endothelial progenitor cells in overweight and obese individuals.
Choi, EY, Lee, H, Woo, JS, Jang, HH, Hwang, SJ, Kim, HS, Kim, WS, Kim, YS, Choue, R, Cha, YJ, et al
Nutrition (Burbank, Los Angeles County, Calif.). 2015;(9):1131-5
Abstract
OBJECTIVES Acute or chronic intake of polyphenol-rich foods has been reported to improve endothelial function. Quercetin, found abundantly in onion, is a potent antioxidant flavonoid. The aim of this study was to investigate whether consumption of onion peel extract (OPE) improves endothelial function in healthy overweight and obese individuals. METHODS This was a randomized double-blind, placebo-controlled study. Seventy-two healthy overweight and obese participants were randomly assigned to receive a red, soft capsule of OPE (100 mg quercetin/d, 50 mg quercetin twice daily; n = 36 participants) or an identical placebo capsule (n = 36) for 12 wk. Endothelial function, defined by flow-mediated dilation (FMD), circulating endothelial progenitor cells (EPCs) by flow cytometry, and laboratory test were determined at baseline and after treatment. RESULTS Baseline characteristics and laboratory findings did not significantly differ between the two groups. Compared with baseline values, the OPE group showed significantly improved FMD at 12 wk (from 12.5 ± 5.2 to 15.2 ± 6.1; P = 0.002), whereas the placebo group showed no difference. Nitroglycerin-mediated dilation did not change in either group. EPC counts (44.2 ± 25.6 versus 52.3 ± 18.6; P = 0.005) and the percentage of EPCs were significantly increased in the OPE group. When FMD was divided into quartiles, rate of patients with endothelial dysfunction defined as lowest quartile (cutoff value, 8.6%) of FMD improved from 26% to 9% by OPE. CONCLUSION Medium-term administration of OPE an improvement in FMD and circulating EPCs.
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Biochemical and clinical correlation of intraplaque neovascularization using contrast-enhanced ultrasound of the carotid artery.
Kim, HS, Woo, JS, Kim, BY, Jang, HH, Hwang, SJ, Kwon, SJ, Choi, EY, Kim, JB, Cheng, X, Jin, E, et al
Atherosclerosis. 2014;(2):579-583
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Abstract
OBJECTIVE Several biomarkers reflecting inflammatory or proteolytic activity have been known to represent plaque vulnerability. Moreover, a recent study confirmed that contrast-enhanced ultrasound (CEUS) can visualize intraplaque neovascularization (IPN) and demonstrate plaque vulnerability. In this study, we tried to demonstrate that IPN detected by CEUS was correlated with several well-known biomarkers and clinical outcome in patients with coronary artery disease (CAD). METHODS Patients with stable CAD were screened by conventional carotid ultrasound and patients with carotid plaque thickness more than 2 mm were performed by CEUS for the presence of IPN. Plasma levels of biomarkers and clinical outcomes were evaluated. RESULTS Among consecutive 89 patients fulfilled the inclusion criteria, 30 patients without IPN (group 1) and 59 patients with IPN (group 2) were analyzed. There were no significant difference in baseline characteristics except for mean age (62.9±10.1 yrs versus 68.4±9.6 yrs, p=0.015). On multivariate analysis, only MMP-9 (p=0.021, 95% CI 1.002-1.027) showed a significant association with IPN. But patients with IPN showed only trend for a history of cardiovascular disease (CVD) (44% versus 30%, p=0.19) and one-year cardiovascular events (CVE) (6.8% versus 3.3%, p=0.50) compared to group 1. Maximum plaque thickness (p=0.04, 95% CI 1.230-6.322) showed a significant correlation with the clinical outcome including CVD or CVE. CONCLUSION MMP-9 correlated with IPN on CEUS. For clinical implication, however, large prospective studies are needed.
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Resting heart rate as predictor for left ventricular dysfunction and heart failure: MESA (Multi-Ethnic Study of Atherosclerosis).
Opdahl, A, Ambale Venkatesh, B, Fernandes, VRS, Wu, CO, Nasir, K, Choi, EY, Almeida, ALC, Rosen, B, Carvalho, B, Edvardsen, T, et al
Journal of the American College of Cardiology. 2014;(12):1182-1189
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Abstract
OBJECTIVES The objective of this study was to investigate the relationship between baseline resting heart rate and incidence of heart failure (HF) and global and regional left ventricular (LV) dysfunction. BACKGROUND The association of resting heart rate to HF and LV function has not been well described in an asymptomatic multi-ethnic population. METHODS Resting heart rate was measured in participants in the MESA (Multi-Ethnic Study of Atherosclerosis) trial at inclusion. Incident HF was registered (n = 176) during follow-up (median 7 years) in those who underwent cardiac magnetic resonance imaging (n = 5,000). Changes in ejection fraction (ΔEF) and peak circumferential strain (Δεcc) were measured as markers of developing global and regional LV dysfunction in 1,056 participants imaged at baseline and 5 years later. Time to HF (Cox model) and Δεcc and ΔEF (multiple linear regression models) were adjusted for demographics, traditional cardiovascular risk factors, calcium score, LV end-diastolic volume, and mass in addition to resting heart rate. RESULTS Cox analysis demonstrated that for 1 beat/min increase in resting heart rate, there was a 4% greater adjusted relative risk for incident HF (hazard ratio: 1.04; 95% CI: 1.02 to 1.06; p < 0.001). Adjusted multiple regression models demonstrated that resting heart rate was positively associated with deteriorating εcc and decrease in EF, even when all coronary heart disease events were excluded from the model. CONCLUSIONS Elevated resting heart rate was associated with increased risk for incident HF in asymptomatic participants in the MESA trial. Higher heart rate was related to development of regional and global LV dysfunction independent of subclinical atherosclerosis and coronary heart disease. (Multi-Ethnic Study of Atherosclerosis [MESA]; NCT00005487).
