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The Role of Exercise in Statin-Associated Muscle Symptoms Outcomes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Mangone, LA, Kwon, OS, Johnson, BT, Wu, Y, Pescatello, LS
Mayo Clinic proceedings. Innovations, quality & outcomes. 2024;(2):131-142
Abstract
OBJECTIVE To provide a synthesis of randomized controlled trials (RCTs) investigating statin-associated muscle symptoms (SAMS) in adults who underwent exercise training intervention. PATIENTS AND METHODS We systematically searched 5 electronic databases for placebo-controlled RCTs through January 31, 2023. We included short-term and long-term exercise interventions that compared the efficacy and safety of exercise+statin vs exercise+placebo in healthy adults and reported SAMS preintervention and postintervention. Publication bias and methodological study quality assessments were performed. RESULTS Five of 454 potentially qualifying RCTs met the inclusion criteria, all short-term exercise RCTs. Participants were predominantly physically inactive young to middle-aged (M=37.2 y) men (57%), 252 (49%) who were on statin therapy, and 271 (53%) on placebo. Of the 3 RCTs providing qualitative SAMS results, 19 (9%) out of 220 participants reported SAMS on exercise+statin and 10 (4%) out of 234 reported SAMS on exercise+placebo. There was no difference between exercise+statin vs exercise+placebo for maximal oxygen consumption (d=-0.18; 95% CI, -0.37 to 0.00; P=.06) or creatine kinase after short-term exercise (d=0.59; 95% CI, -0.06 to 1.25; P=.08). Participants in the exercise+statin group reduced low-density lipoprotein cholesterol vs exercise+placebo (d=-1.84; 95% CI, -2.28 to -1.39; P<.001). Most of the RCTs exhibited low levels of risk of bias (k=4, 80%) and achieved moderate methodological study quality (75.0%±5.2%). CONCLUSION Self-reported SAMs tended to be 5% greater after short-term exercise in statin users compared with placebo, although this difference did not achieve statistical significance. There remains an important need for placebo-controlled RCTs investigating the prevalence of statin-induced SAMS during exercise training.
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Reliability of the passive leg movement assessment of vascular function in men.
Groot, HJ, Broxterman, RM, Gifford, JR, Garten, RS, Rossman, MJ, Jarrett, CL, Kwon, OS, Hydren, JR, Richardson, RS
Experimental physiology. 2022;(5):541-552
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Abstract
NEW FINDINGS What is the central question of this study? Use of the passive leg movement (PLM) test, a non-invasive assessment of microvascular function, is on the rise. However, PLM reliability in men has not been adequately investigated, nor has such reliability data, in men, been compared to the most commonly employed vascular function assessment, flow-mediated vasodilation (FMD). What is the main finding and its importance? PLM is a reliable method to assess vascular function in men, and is comparable to values previously reported for PLM in women, and for FMD. Given the importance of vascular function as a predictor of cardiovascular disease risk, these data support the utility of PLM as a clinically relevant measurement. ABSTRACT Although vascular function is an independent predictor of cardiovascular disease risk, and therefore has significant prognostic value, there is currently not a single clinically accepted method of assessment. The passive leg movement (PLM) assessment predominantly reflects microvascular endothelium-dependent vasodilation and can identify decrements in vascular function with advancing age and pathology. Reliability of the PLM model was only recently determined in women, and has not been adequately investigated in men. Twenty healthy men (age: 27 ± 2 year) were studied on three separate experimental days, resulting in three within-day and three between-day trials. The hyperemic response to PLM was assessed with Doppler ultrasound, and expressed as the absolute peak in leg blood flow (LBFpeak ), change from baseline to peak (ΔLBFpeak ), absolute area under the curve (LBFAUC ), and change in AUC from baseline (ΔLBFAUC ). PLM-induced hyperemia yielded within-day coefficients of variation (CV) from 10.9 to 22.9%, intraclass correlation coefficients (ICC) from 0.82 to 0.90, standard error of the measurement (SEM) from 8.3 to 17.2%, and Pearson's correlation coefficients (r) from 0.56 to 0.81. Between-day assessments of PLM hyperemia resulted in CV from 14.4 to 25%, ICC from 0.75 to 0.87, SEM from 9.8 to 19.8%, and r from 0.46 to 0.75. Similar to previous reports in women, the hyperemic responses to PLM in men display moderate-to-high reliability, and are comparable to reliability data for brachial artery flow mediated vasodilation. These positive reliability findings further support the utility of PLM as a clinical measurement of vascular function and cardiovascular disease risk.
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Physical activity can reduce the prevalence of gallstone disease among males: An observational study.
Kwon, OS, Kim, YK, Her, KH, Kim, HJ, Lee, SD
Medicine. 2020;99(26):e20763
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Plain language summary
Gallstone disease (GD) is one of the most common digestive disorders and can cause acute abdominal pain, jaundice, and abnormal liver function due to stones deposited in the gallbladder or bile ducts. Metabolic syndrome is a known risk factor for GD and physical activity (PA) can reduce the incidence of metabolic syndrome. The aim of this observational study was to evaluate whether PA can reduce the risk of GD in a Korean population. 8908 subjects were included in this study, GD was diagnosed by ultrasound and PA was defined as moderate-intensity aerobic PA for at least 150 minutes, or vigorous-intensity activity for at least 75 minutes throughout the week. Participants underwent physical investigation and had blood samples taken to establish metabolic syndrome markers. In men, PA, old age and higher AST (aspartate aminotransferase, a liver enzyme) were independent risk factors for GD, whilst in women only a history of non-alcoholic fatty liver disease, but not PA, was independently associated with GD.
Abstract
Several previous studies have reported that physical activity (PA) levels can independently affect the prevalence of gallstone disease (GD) in Western countries. However, this association has not been reported in Eastern countries. Therefore, this study aimed to determine whether PA is an independent determinant of GD prevalence in a Korean population, according to the World Health Organizations Global Recommendations on PA for Health.A total of 8908 subjects who completed a questionnaire underwent medical examination and ultrasound scanning at the Health Promotion Center of the Jeju National University Hospital between January 2009 and December 2018. GD and fatty liver disease were diagnosed by abdominal ultrasound. Biochemical parameters and body mass index were determined, and metabolic syndrome status, age, and PA levels were extracted from medical records. Univariate and multivariate analyses were performed to identify independent factors affecting GD.The estimated rates of PA and GD among male subjects were 23.7% and 4.6%, whereas the rates among females were 18.4% and 4.2%, respectively. Multivariate analysis suggested that no PA, old age, and higher aspartate aminotransferase level in males and nonalcoholic fatty liver disease status in females were independent factors affecting GD.In our study, PA was associated with a reduction in GD among males but not females.
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Sorafenib with or without concurrent transarterial chemoembolization in patients with advanced hepatocellular carcinoma: The phase III STAH trial.
Park, JW, Kim, YJ, Kim, DY, Bae, SH, Paik, SW, Lee, YJ, Kim, HY, Lee, HC, Han, SY, Cheong, JY, et al
Journal of hepatology. 2019;(4):684-691
Abstract
BACKGROUND & AIMS Sorafenib is first-line standard of care for patients with advanced hepatocellular carcinoma (HCC), yet it confers limited survival benefit. Therefore, we aimed to compare clinical outcomes of sorafenib combined with concurrent conventional transarterial chemoembolization (cTACE) vs. sorafenib alone in patients with advanced HCC. METHODS In this investigator-initiated, multicenter, phase III trial, patients were randomized to receive sorafenib alone (Arm S, n = 169) or in combination with cTACE on demand (Arm C, n = 170). Sorafenib was started within 3 days and cTACE within 7-21 days of randomization. The primary endpoint was overall survival (OS). RESULTS For Arms C and S, the median OS was 12.8 vs. 10.8 months (hazard ratio [HR] 0.91; 90% CI 0.69-1.21; p = 0.290); median time to progression, 5.3 vs. 3.5 months (HR 0.67; 90% CI 0.53-0.85; p = 0.003); median progression-free survival, 5.2 vs. 3.6 months (HR 0.73; 90% CI 0.59-0.91; p = 0.01); and tumor response rate, 60.6% vs. 47.3% (p = 0.005). For Arms C and S, serious (grade ≥3) adverse events occurred in 33.3% vs. 19.8% (p = 0.006) of patients and included increased alanine aminotransferase levels (20.3% vs. 3.6%), hyperbilirubinemia (11.8% vs. 3.0%), ascites (11.8% vs. 4.2%), thrombocytopenia (7.2% vs. 1.2%), anorexia (7.2% vs. 1.2%), and hand-foot skin reaction (10.5% vs. 11.4%). A post hoc subgroup analysis compared OS in Arm C patients (46.4%) receiving ≥2 cTACE sessions to Arm S patients (18.6 vs. 10.8 months; HR 0.58; 95% CI 0.40-0.82; p = 0.006). CONCLUSION Compared with sorafenib alone, sorafenib combined with cTACE did not improve OS in patients with advanced HCC. However, sorafenib combined with cTACE significantly improved time to progression, progression-free survival, and tumor response rate. Sorafenib alone remains the first-line standard of care for patients with advanced HCC. LAY SUMMARY For patients with advanced hepatocellular carcinoma requiring sorafenib therapy, co-administration with conventional transarterial chemoembolization did not improve overall survival compared to sorafenib alone. Therefore, sorafenib alone remains the first-line standard of care for patients with advanced hepatocellular carcinoma. Clinical Trial Number: NCT01829035.
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Oxygen delivery and the restoration of the muscle energetic balance following exercise: implications for delayed muscle recovery in patients with COPD.
Layec, G, Hart, CR, Trinity, JD, Kwon, OS, Rossman, MJ, Broxterman, RM, Le Fur, Y, Jeong, EK, Richardson, RS
American journal of physiology. Endocrinology and metabolism. 2017;(1):E94-E104
Abstract
Patients with chronic obstructive pulmonary disease (COPD) experience a delayed recovery from skeletal muscle fatigue following exhaustive exercise that likely contributes to their progressive loss of mobility. As this phenomenon is not well understood, this study sought to examine postexercise peripheral oxygen (O2) transport and muscle metabolism dynamics in patients with COPD, two important determinants of muscle recovery. Twenty-four subjects, 12 nonhypoxemic patients with COPD and 12 healthy subjects with a sedentary lifestyle, performed dynamic plantar flexion exercise at 40% of the maximal work rate (WRmax) with phosphorus magnetic resonance spectroscopy (31P-MRS), near-infrared spectroscopy (NIRS), and vascular Doppler ultrasound assessments. The mean response time of limb blood flow at the offset of exercise was significantly prolonged in patients with COPD (controls: 56 ± 27 s; COPD 120 ± 87 s; P < 0.05). In contrast, the postexercise time constant for capillary blood flow was not significantly different between groups (controls: 49 ± 23 s; COPD 51 ± 21 s; P > 0.05). The initial postexercise convective O2 delivery (controls: 0.15 ± 0.06 l/min; COPD 0.15 ± 0.06 l/min) and the corresponding oxidative adenosine triphosphate (ATP) demand (controls: 14 ± 6 mM/min; COPD 14 ± 6 mM/min) in the calf were not significantly different between controls and patients with COPD (P > 0.05). The phosphocreatine resynthesis time constant (controls: 46 ± 20 s; COPD 49 ± 21 s), peak mitochondrial phosphorylation rate, and initial proton efflux were also not significantly different between groups (P > 0.05). Therefore, despite perturbed peripheral hemodynamics, intracellular O2 availability, proton efflux, and aerobic metabolism recovery in the skeletal muscle of nonhypoxemic patients with COPD are preserved following plantar flexion exercise and thus are unlikely to contribute to the delayed recovery from exercise in this population.
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Clinical efficacies of topical agents for the treatment of seborrheic dermatitis of the scalp: a comparative study.
Shin, H, Kwon, OS, Won, CH, Kim, BJ, Lee, YW, Choe, YB, Ahn, KJ, Eun, HC
The Journal of dermatology. 2009;(3):131-7
Abstract
Previous studies have shown that topical steroid and shampoo containing zinc pyrithione provide clinical benefits for treatment of scalp seborrheic dermatitis. But the clinical efficacy of topical tacrolimus, a newly developed calcineurin inhibitor on seborrheic dermatitis, is not well investigated yet. We wanted to compare the clinical efficacy of topical tacrolimus with that of conventional treatment (zinc pyrithione shampoo and topical betamethasone) for treatment of seborrheic dermatitis of the scalp. Patients with seborrheic dermatitis of the scalp were randomly allocated to receive topical betamethasone, topical tacrolimus or zinc pyrithione shampoo. Some patients were instructed to continue the treatments for 8 weeks and the others to discontinue the treatments at week 4. We evaluated the efficacy using a clinical severity score, dandruff score and sebum secretion at baseline, week 4 and week 8. All treatment groups showed significant improvements in clinical assessment after 4 weeks. While the patients treated by zinc pyrithione improved continuously even after cessation of the treatment, the patients treated by betamethasone lotion or tacrolimus ointment were aggravated clinically. Topical tacrolimus was as effective as topical betamethasone, and showed more prolonged remission than topical betamethasone. To treat seborrheic dermatitis of the scalp, we think that the combination therapy of topical steroid or topical tacrolimus, and zinc pyrithione is recommended.
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Human hair growth enhancement in vitro by green tea epigallocatechin-3-gallate (EGCG).
Kwon, OS, Han, JH, Yoo, HG, Chung, JH, Cho, KH, Eun, HC, Kim, KH
Phytomedicine : international journal of phytotherapy and phytopharmacology. 2007;(7-8):551-5
Abstract
Green tea is a popular worldwide beverage, and its potential beneficial effects such as anti-cancer and anti-oxidant properties are believed to be mediated by epigallocatechin-3-gallate (EGCG), a major constituent of polyphenols. Recently, it was reported that EGCG might be useful in the prevention or treatment of androgenetic alopecia by selectively inhibiting 5alpha-reductase activity. However, no report has been issued to date on the effect of EGCG on human hair growth. This study was undertaken to measure the effect of EGCG on hair growth in vitro and to investigate its effect on human dermal papilla cells (DPCs) in vivo and in vitro. EGCG promoted hair growth in hair follicles ex vivo culture and the proliferation of cultured DPCs. The growth stimulation of DPCs by EGCG in vitro may be mediated through the upregulations of phosphorylated Erk and Akt and by an increase in the ratio of Bcl-2/Bax ratio. Similar results were also obtained in in vivo dermal papillae of human scalps. Thus, we suggest that EGCG stimulates human hair growth through these dual proliferative and anti-apoptotic effects on DPCs.
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HPLC determination and pharmacokinetics of endogenous acetyl-L-carnitine (ALC) in human volunteers orally administered a single dose of ALC.
Kwon, OS, Chung, YB
Archives of pharmacal research. 2004;(6):676-81
Abstract
Acetyl-L-carnitine (ALC), a naturally occurring endogenous compound, has been shown to improve the cognitive performance of patients with senile dementia Alzheimer's type, and to be involved in cholinergic neurotransmission. Because ALC is an endogenous compound, validation of the analytical methods of ALC in the biological fluids is very important and difficult. This study was presented validation and correction for plasma ALC concentrations and pharmacokinetics after oral administration of ALC to human volunteers. ALC concentrations in human plasma were corrected by subtracting the concentration of blank plasma from each sample. Precision and accuracy (bias %) for uncorrected ALC concentrations were below 2.6 and 6.5% for intra-days, and 4.0 and 9.4% for inter-days, respectively. Precision and accuracy (bias %) for corrected ALC concentrations were below 10.9 and 6.0% for intra-days, and 10.5 and 16.9% for inter-days, respectively. Quantitation limit was 0.1 microg/mL. After oral administration of a 500 mg ALC tablet to 8 healthy volunteers, the principle pharmacokinetic parameters were 4.2 h of the half-life (t(1/2,beta)), the area under the curve (AUC(0-8)) of 9.88 microg.h/mL, and 3.1 h of the time (Tmax) to reach Cmax. This study first describes the pharmacokinetic study after oral administration of a single dose of ALC in human volunteers.