Kangbuk Samsung Hospital

Abstract The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-19 1,2 , host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases 3–7 . They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.

PURPOSE: To retrospectively evaluate the diagnostic accuracy of ultrasonographic (US) criteria for the depiction of benign and malignant thyroid nodules by using tissue diagnosis as the reference standard. MATERIALS AND METHODS: This study had institutional review board approval, and informed consent was waived. From January 2003 through June 2003, 8024 consecutive patients had undergone thyroid US at nine affiliated hospitals. A total of 831 patients (716 women, 115 men; mean age, 49.5 years +/- 13.8 [standard deviation]) with 849 nodules (360 malignant, 489 benign) that were diagnosed at surgery or biopsy were included in this study. Three radiologists retrospectively evaluated the following characteristics on US images: nodule size, presence of spongiform appearance, shape, margin, echotexture, echogenicity, and presence of microcalcification, macrocalcification, or rim calcification. A chi(2) test and multiple regression analysis were performed. Sensitivity, specificity, and positive and negative predictive values were obtained. RESULTS: Statistically significant (P < .05) findings of malignancy were a taller-than-wide shape (sensitivity, 40.0%; specificity, 91.4%), a spiculated margin (sensitivity, 48.3%; specificity, 91.8%), marked hypoechogenicity (sensitivity, 41.4%; specificity, 92.2%), microcalcification (sensitivity, 44.2%; specificity, 90.8%), and macrocalcification (sensitivity, 9.7%; specificity, 96.1%). The US findings for benign nodules were isoechogenicity (sensitivity, 56.6%; specificity, 88.1%; P < .001) and a spongiform appearance (sensitivity, 10.4%; specificity, 99.7%; P < .001). The presence of at least one malignant US finding had a sensitivity of 83.3%, a specificity of 74.0%, and a diagnostic accuracy of 78.0%. For thyroid nodules with a diameter of 1 cm or less, the sensitivity of microcalcifications was lower than that in larger nodules (36.6% vs 51.4%, P < .05). CONCLUSION: Shape, margin, echogenicity, and presence of calcification are helpful criteria for the discrimination of malignant from benign nodules; the diagnostic accuracy of US criteria is dependent on tumor size.

The rate of detection of thyroid nodules and carcinomas has increased with the widespread use of ultrasonography (US), which is the mainstay for the detection and risk stratification of thyroid nodules as well as for providing guidance for their biopsy and nonsurgical treatment. The Korean Society of Thyroid Radiology (KSThR) published their first recommendations for the US-based diagnosis and management of thyroid nodules in 2011. These recommendations have been used as the standard guidelines for the past several years in Korea. Lately, the application of US has been further emphasized for the personalized management of patients with thyroid nodules. The Task Force on Thyroid Nodules of the KSThR has revised the recommendations for the ultrasound diagnosis and imaging-based management of thyroid nodules. The review and recommendations in this report have been based on a comprehensive analysis of the current literature and the consensus of experts.

Abstract Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40–50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes 1 . Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel 2 ) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10–20% (14–24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.

Non-alcoholic fatty liver disease (NAFLD) is a potentially serious liver disease that affects approximately one-quarter of the global adult population, causing a substantial burden of ill health with wide-ranging social and economic implications. It is a multisystem disease and is considered the hepatic component of metabolic syndrome. Unlike other highly prevalent conditions, NAFLD has received little attention from the global public health community. Health system and public health responses to NAFLD have been weak and fragmented, and, despite its pervasiveness, NAFLD is largely unknown outside hepatology and gastroenterology. There is only a nascent global public health movement addressing NAFLD, and the disease is absent from nearly all national and international strategies and policies for non-communicable diseases, including obesity. In this global Delphi study, a multidisciplinary group of experts developed consensus statements and recommendations, which a larger group of collaborators reviewed over three rounds until consensus was achieved. The resulting consensus statements and recommendations address a broad range of topics - from epidemiology, awareness, care and treatment to public health policies and leadership - that have general relevance for policy-makers, health-care practitioners, civil society groups, research institutions and affected populations. These recommendations should provide a strong foundation for a comprehensive public health response to NAFLD.

BACKGROUND: Chronic kidney disease (CKD) is a frequent, under-recognized condition and a risk factor for renal failure and cardiovascular disease. Increasing evidence connects non-alcoholic fatty liver disease (NAFLD) to CKD. We conducted a meta-analysis to determine whether the presence and severity of NAFLD are associated with the presence and severity of CKD. METHODS AND FINDINGS: English and non-English articles from international online databases from 1980 through January 31, 2014 were searched. Observational studies assessing NAFLD by histology, imaging, or biochemistry and defining CKD as either estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 or proteinuria were included. Two reviewers extracted studies independently and in duplicate. Individual participant data (IPD) were solicited from all selected studies. Studies providing IPD were combined with studies providing only aggregate data with the two-stage method. Main outcomes were pooled using random-effects models. Sensitivity and subgroup analyses were used to explore sources of heterogeneity and the effect of potential confounders. The influences of age, whole-body/abdominal obesity, homeostasis model of insulin resistance (HOMA-IR), and duration of follow-up on effect estimates were assessed by meta-regression. Thirty-three studies (63,902 participants, 16 population-based and 17 hospital-based, 20 cross-sectional, and 13 longitudinal) were included. For 20 studies (61% of included studies, 11 cross-sectional and nine longitudinal, 29,282 participants), we obtained IPD. NAFLD was associated with an increased risk of prevalent (odds ratio [OR] 2.12, 95% CI 1.69-2.66) and incident (hazard ratio [HR] 1.79, 95% CI 1.65-1.95) CKD. Non-alcoholic steatohepatitis (NASH) was associated with a higher prevalence (OR 2.53, 95% CI 1.58-4.05) and incidence (HR 2.12, 95% CI 1.42-3.17) of CKD than simple steatosis. Advanced fibrosis was associated with a higher prevalence (OR 5.20, 95% CI 3.14-8.61) and incidence (HR 3.29, 95% CI 2.30-4.71) of CKD than non-advanced fibrosis. In all analyses, the magnitude and direction of effects remained unaffected by diabetes status, after adjustment for other risk factors, and in other subgroup and meta-regression analyses. In cross-sectional and longitudinal studies, the severity of NAFLD was positively associated with CKD stages. Limitations of analysis are the relatively small size of studies utilizing liver histology and the suboptimal sensitivity of ultrasound and biochemistry for NAFLD detection in population-based studies. CONCLUSION: The presence and severity of NAFLD are associated with an increased risk and severity of CKD. Please see later in the article for the Editors' Summary.

Obesity is a prevalent and complex disease. The prevalence of obesity in Korea increased from 29.7% in 2010 to 35.7% in 2018, with the prevalence of abdominal obesity being 23.8% in 2018. Obesity contributes to medical costs and socioeconomic burden due to associated comorbidities. The treatment and management of obesity is changing based on new clinical evidence. The 2020 Korean Society for the Study of Obesity Guideline for the Management of Obesity in Korea summarizes evidence-based recommendations and treatment guidelines.

BACKGROUND: The National Health Insurance Service (NHIS) recently signed an agreement to provide limited open access to the databases within the Korean Diabetes Association for the benefit of Korean subjects with diabetes. Here, we present the history, structure, contents, and way to use data procurement in the Korean National Health Insurance (NHI) system for the benefit of Korean researchers. METHODS: The NHIS in Korea is a single-payer program and is mandatory for all residents in Korea. The three main healthcare programs of the NHI, Medical Aid, and long-term care insurance (LTCI) provide 100% coverage for the Korean population. The NHIS in Korea has adopted a fee-for-service system to pay health providers. Researchers can obtain health information from the four databases of the insured that contain data on health insurance claims, health check-ups and LTCI. RESULTS: Metabolic disease as chronic disease is increasing with aging society. NHIS data is based on mandatory, serial population data, so, this might show the time course of disease and predict some disease progress, and also be used in primary and secondary prevention of disease after data mining. CONCLUSION: The NHIS database represents the entire Korean population and can be used as a population-based database. The integrated information technology of the NHIS database makes it a world-leading population-based epidemiology and disease research platform.

Thermal ablation using radiofrequency is a new, minimally invasive modality employed as an alternative to surgery in patients with benign thyroid nodules and recurrent thyroid cancers. The Task Force Committee of the Korean Society of Thyroid Radiology (KSThR) developed recommendations for the optimal use of radiofrequency ablation for thyroid tumors in 2012. As new meaningful evidences have accumulated, KSThR decided to revise the guidelines. The revised guideline is based on a comprehensive analysis of the current literature and expert consensus.

Importance: Data on P2Y12 inhibitor monotherapy after short-duration dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention are limited. Objective: To determine whether P2Y12 inhibitor monotherapy after 3 months of DAPT is noninferior to 12 months of DAPT in patients undergoing PCI. Design, Setting, and Participants: The SMART-CHOICE trial was an open-label, noninferiority, randomized study that was conducted in 33 hospitals in Korea and included 2993 patients undergoing PCI with drug-eluting stents. Enrollment began March 18, 2014, and follow-up was completed July 19, 2018. Interventions: Patients were randomly assigned to receive aspirin plus a P2Y12 inhibitor for 3 months and thereafter P2Y12 inhibitor alone (n = 1495) or DAPT for 12 months (n = 1498). Main Outcomes and Measures: The primary end point was major adverse cardiac and cerebrovascular events (a composite of all-cause death, myocardial infarction, or stroke) at 12 months after the index procedure. Secondary end points included the components of the primary end point and bleeding defined as Bleeding Academic Research Consortium type 2 to 5. The noninferiority margin was 1.8%. Results: Among 2993 patients who were randomized (mean age, 64 years; 795 women [26.6%]), 2912 (97.3%) completed the trial. Adherence to the study protocol was 79.3% of the P2Y12 inhibitor monotherapy group and 95.2% of the DAPT group. At 12 months, major adverse cardiac and cerebrovascular events occurred in 42 patients in the P2Y12 inhibitor monotherapy group and in 36 patients in the DAPT group (2.9% vs 2.5%; difference, 0.4% [1-sided 95% CI, -∞% to 1.3%]; P = .007 for noninferiority). There were no significant differences in all-cause death (21 [1.4%] vs 18 [1.2%]; hazard ratio [HR], 1.18; 95% CI, 0.63-2.21; P = .61), myocardial infarction (11 [0.8%] vs 17 [1.2%]; HR, 0.66; 95% CI, 0.31-1.40; P = .28), or stroke (11 [0.8%] vs 5 [0.3%]; HR, 2.23; 95% CI, 0.78-6.43; P = .14) between the 2 groups. The rate of bleeding was significantly lower in the P2Y12 inhibitor monotherapy group than in the DAPT group (2.0% vs 3.4%; HR, 0.58; 95% CI, 0.36-0.92; P = .02). Conclusions and Relevance: Among patients undergoing percutaneous coronary intervention, P2Y12 inhibitor monotherapy after 3 months of DAPT compared with prolonged DAPT resulted in noninferior rates of major adverse cardiac and cerebrovascular events. Because of limitations in the study population and adherence, further research is needed in other populations. Trial Registration: ClinicalTrials.gov Identifier: NCT02079194.

The current recommendations for the treatment of obese people include increased physical activity and reduced calories intake. When the behavioral approach is not sufficient, a pharmacologic treatment is recommended. In past years, numerous drugs have been approved for the treatment of obesity; however, most of them have been withdrawn from the market because of their adverse effects. In fact, amphetamine, rimonabant and sibutramine licenses have been withdrawn due to an increased risk of psychiatric disorders and non-fatal myocardial infarction or stroke. Even if orlistat is not as effective as other drugs in reducing body weight, orlistat is presently the only available choice for the treatment of obesity because of its safety for cardiovascular events and positive effects on diabetic control. Hopefully, more effective and better tolerated anti-obesity drugs will be developed through an improved understanding of the multiple mechanisms and complex physiological systems targeting appetite.

Introduction: A low body mass index (BMI) is associated with increased mortality and low health-related quality of life in patients with COPD. The Asia-Pacific classification of BMI has a lower cutoff for overweight and obese categories compared to the World Health Organization (WHO) classification. The present study assessed patients with COPD among different BMI categories according to two BMI classification systems: WHO and Asia-Pacific. Patients and methods: Patients with COPD aged 40 years or older from the Korean COPD Subtype Study cohort were selected for evaluation. We enrolled 1,462 patients. Medical history including age, sex, St George’s Respiratory Questionnaire (SGRQ-C), the modified Medical Research Council (mMRC) dyspnea scale, and post-bronchodilator forced expiratory volume in 1 second (FEV 1 ) were evaluated. Patients were categorized into different BMI groups according to the two BMI classification systems. Result: FEV 1 and the diffusing capacity of the lung for carbon monoxide (DLCO) percentage revealed an inverse “U”-shaped pattern as the BMI groups changed from underweight to obese when WHO cutoffs were applied. When Asia-Pacific cutoffs were applied, FEV 1 and DLCO (%) exhibited a linearly ascending relationship as the BMI increased, and the percentage of patients in the overweight and obese groups linearly decreased with increasing severity of the Global Initiative for Chronic Obstructive Lung Disease criteria. From the underweight to the overweight groups, SGRQ-C and mMRC had a decreasing relationship in both the WHO and Asia-Pacific classifications. The prevalence of comorbidities in the different BMI groups showed similar trends in both BMI classifications systems. Conclusion: The present study demonstrated that patients with COPD who have a high BMI have better pulmonary function and health-related quality of life and reduced dyspnea symptoms. Furthermore, the Asia-Pacific BMI classification more appropriately reflects the correlation of obesity and disease manifestation in Asian COPD patients than the WHO classification. Keywords: body mass index, COPD, comorbidity

BACKGROUND: Data regarding clinical outcomes after intravascular imaging-guided percutaneous coronary intervention (PCI) for complex coronary-artery lesions, as compared with outcomes after angiography-guided PCI, are limited. METHODS: In this prospective, multicenter, open-label trial in South Korea, we randomly assigned patients with complex coronary-artery lesions in a 2:1 ratio to undergo either intravascular imaging-guided PCI or angiography-guided PCI. In the intravascular imaging group, the choice between intravascular ultrasonography and optical coherence tomography was at the operators' discretion. The primary end point was a composite of death from cardiac causes, target-vessel-related myocardial infarction, or clinically driven target-vessel revascularization. Safety was also assessed. RESULTS: A total of 1639 patients underwent randomization, with 1092 assigned to undergo intravascular imaging-guided PCI and 547 assigned to undergo angiography-guided PCI. At a median follow-up of 2.1 years (interquartile range, 1.4 to 3.0), a primary end-point event had occurred in 76 patients (cumulative incidence, 7.7%) in the intravascular imaging group and in 60 patients (cumulative incidence, 12.3%) in the angiography group (hazard ratio, 0.64; 95% confidence interval, 0.45 to 0.89; P = 0.008). Death from cardiac causes occurred in 16 patients (cumulative incidence, 1.7%) in the intravascular imaging group and in 17 patients (cumulative incidence, 3.8%) in the angiography group; target-vessel-related myocardial infarction occurred in 38 (cumulative incidence, 3.7%) and 30 (cumulative incidence, 5.6%), respectively; and clinically driven target-vessel revascularization in 32 (cumulative incidence, 3.4%) and 25 (cumulative incidence, 5.5%), respectively. There were no apparent between-group differences in the incidence of procedure-related safety events. CONCLUSIONS: Among patients with complex coronary-artery lesions, intravascular imaging-guided PCI led to a lower risk of a composite of death from cardiac causes, target-vessel-related myocardial infarction, or clinically driven target-vessel revascularization than angiography-guided PCI. (Supported by Abbott Vascular and Boston Scientific; RENOVATE-COMPLEX-PCI ClinicalTrials.gov number, NCT03381872).

BACKGROUND: The triglyceride glucose (TyG) index is an inexpensive clinical surrogate marker for insulin resistance. However, the relationship between TyG index and atherosclerotic cardiovascular disease (CVD) remains unclear. We evaluated the relationship between TyG index and CVD using a large-scale population dataset from the National Health Information Database (NHID). METHODS: We performed a retrospective observational cohort study of 5,593,134 persons older than 40 years from 2009 to 2017 using the NHID. We divided the participants into TyG index quartiles. Outcome variables were stroke, myocardial infarction, and both. The incidence of outcomes was estimated for each TyG quartile over the total follow-up period. All outcomes were analyzed by Cox proportional hazards regression analysis while controlling for baseline covariates. RESULTS: During 8.2 years of mean follow-up, stroke was diagnosed in 89,120 (1.59%), MI in 62,577 (1.12%), and both stroke and MI in 146,744 (2.62%) participants. Multivariate-adjusted hazard ratios (HRs) for patients in the highest TyG index quartile demonstrated that these patients were at higher risk for stroke (HR = 1.259; 95% confidence interval [CI] 1.233-1.286), for MI (HR = 1.313; 95% CI 1.28-1.346), and for both (HR = 1.282; 95% CI 1.261-1.303) compared with participants in the lowest TyG index quartile. These effects were independent of age, sex, smoking, alcohol consumption, physical activity, body mass index, systolic blood pressure, and total cholesterol. CONCLUSIONS: In our large population study, TyG index, a simple measure reflecting insulin resistance, was potentially useful in the early identification of individuals at high risk of experiencing a cardiovascular event.

BACKGROUND AND AIM: Differences in the prevalence of non-alcoholic fatty liver disease (NAFLD) between Eastern and Western populations are primarily attributable to differences in definitions and biased population selection. Thus, the aim of the present study was to accurately determine the actual prevalence of NAFLD by sonography and to characterize the risk factors for NAFLD. METHODS: The present cross-sectional study was performed with data obtained from 6,648 subjects, all of whom were older than 20 years of age (3,530 men and 3,118 women). The term 'non-drinker' was applied to men who consumed less than 30 g alcohol/day and to women who consumed less than 20 g alcohol/day. Non-alcoholic fatty liver disease was defined as a sonographically detected fatty liver in the absence of viral hepatitis in a non-drinker. RESULTS: Of the 1,613 subjects who were diagnosed with sonographic fatty liver, 1,240 were non-drinkers and had no viral hepatitis. Overall, the unadjusted and age-adjusted prevalences of NAFLD were 18.7% (23% in men, 13.7% in women) and 16.1% (21.6% in men, 11.2% in women), respectively. Multivariate analysis revealed that several risk factors were profoundly associated with the prevalence of NAFLD, including obesity, insulin resistance, hyperlipidemia and hyperglycemia in both genders, as well as age, menopausal status and estrogen medication in women only. CONCLUSIONS: These results demonstrate that the prevalence of NAFLD in Korean adults, according to sonographic surveys, is comparable to that seen in more developed countries. From the perspective of increasing obesity, the high prevalence rates noted in the study may herald an increased burden of chronic liver disease in the Korean population.

Adipose-derived stem cells (ADSCs) have been shown to induce wound-healing effects. Because inflammation near the wound area induces oxygen deficiency, it is interesting to elucidate the effect of hypoxia on the function of ADSCs. In this work, we asked: (1) does hypoxia alter the wound-healing function of ADSCs? and (2) what are the major factors responsible for the alteration in the wound-healing function? Effect of hypoxia on the proliferation of ADSCs was first examined that hypoxia (2% O(2)) enhanced the proliferation of ADSCs in either the presence of serum or in the absence of serum. The conditioned medium of ADSCs harvested under hypoxia (hypoCM) significantly promoted collagen synthesis and the migration of human dermal fibroblasts, compared with that in normoxia (norCM). In the animal studies, hypoCM significantly reduced the wound area compared with norCM. Furthermore, mRNA and protein measurements showed that hypoxia up-regulated growth factors such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Inhibition of VEGF and bFGF using neutralizing antibodies reversed the migration of the wounded human dermal fibroblasts and the healing of wounds in animal experiment. Collectively, these results suggest that hypoxia increases the proliferation of ADSCs and enhances the wound-healing function of ADSCs, at least partly, by up-regulating the secretion of VEGF and bFGF.

BACKGROUND: Associations between hyperuricemia, cardiovascular diseases and diabetes have been reported, but few of the studies have been conducted in the Korean population. The present study examined a Korean adult population with respect to the relationships between serum uric acid concentrations and hypertension, insulin resistance, and the risk factors of metabolic syndrome. METHODS AND RESULTS: A total of 53,477 subjects were divided into 4 groups according to serum uric acid quartiles. The incidence of hypertension in all subjects was higher in the first quartile than in the third plus fourth quartile (odds ratio (OR) 1.192, p < 0.001). Homeostasis model assessment index was found to be associated with serum uric acid concentration in all subjects (OR 1.193, p < 0.001), and the serum uric acid concentration was positively correlated with the risk factors of metabolic syndrome. In addition, the number of metabolic syndrome variables increased as serum uric acid concentration increased. CONCLUSIONS: Serum uric acid concentration was found to be independently correlated with hypertension, insulin resistance and the risk factors of metabolic syndrome. In addition, even those with a serum uric acid concentration in the normal range showed an increased risk of metabolic syndrome as serum uric acid concentration increased.

Ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E) have antioxidant properties that could improve redox-sensitive vascular changes associated with hypertension. We determined whether vitamins C and E influence vascular function and structure in hypertension by modulating activity of NADPH oxidase and superoxide dismutase (SOD). Adult stroke-prone spontaneously hypertensive rats (SHRSP) were divided into 3 groups: control (C; n=6), vitamin C-treated (vit C, 1000 mg/day; n=7), and vitamin E-treated (vit E, 1000 IU/day; n=8). All rats were fed 4% NaCl. Blood pressure was measured weekly. After 6 weeks of treatment, the rats were killed, and mesenteric arteries were mounted as pressurized preparations. Vascular O(2)(-) generation and NADPH oxidase activity were measured by chemiluminescence. Vascular SOD activity and plasma total antioxidant status (TAS) were determined spectrophotometrically. Blood pressure increased from 212+/-7 to 265+/-6 mm Hg in controls. Treatment prevented progression of hypertension (vit C, 222+/-6 to 234+/-14 mm Hg; vit E, 220+/-9 to 227+/-10 mm Hg). Acetylcholine-induced vasodilation was improved (P<0.05), and media-to-lumen ratio was reduced (P<0.05) in the treated rats. O(2)(-) was lower in vitamin-treated groups compared with controls (vit C, 10+/-4 nmol. min(-1). g(-1) dry tissue weight; vit E, 9.6+/-3.5 nmol. min(-1). g(-1) dry tissue weight; C, 21+/-9 nmol. min(-1). g(-1) dry tissue weight; P<0.05). Both vitamin-treated groups showed significant improvement (P<0.01) in TAS. These effects were associated with decreased activation of vascular NADPH oxidase (vit C, 46+/-10; vit E, 50+/-9; C, 70+/-16 nmol. min(-1). g(-1) dry tissue weight, P<0.05) and increased activation of SOD (vit C, 12+/-2; vit E, 8+/-1; C, 4.6+/-1 U/mg; P<0.05). Our results demonstrate that vitamins C and E reduce oxidative stress, improve vascular function and structure, and prevent progression of hypertension in SHRSP. These effects may be mediated via modulation of enzyme systems that generate free radicals.

BACKGROUND: Procedural results for percutaneous coronary intervention (PCI) in coronary vessels with chronic total occlusion (CTO) have improved in recent years, and PCI strategies have moved toward more complete revascularization with more liberal use of CTO-PCI. However, evidence evaluating CTO-PCI is limited to observational studies and small clinical trials. METHODS: In this open-label, multicenter, randomized, noninferiority trial, PCI-eligible patients were assigned to receive either 1 of 2 strategies: PCI or no PCI for the qualifying de novo CTO lesion with the option for PCI of obstructive non-CTO lesions at the discretion of the operator. The primary end point was a composite of death, myocardial infarction, stroke, or any revascularization. Health-related quality of life was assessed at baseline and at 1, 6, 12, 24, and 36 months. Because of slow recruitment, the trial was stopped before completion of the 1284 planned enrollments. RESULTS: Between March 2010 and September 2016, 834 patients were randomly assigned to the CTO-PCI (n=417) or no CTO-PCI (n=398) strategy. Among the patients assigned to the no CTO-PCI strategy, 78 (19.6%) crossed over to receive staged CTO-PCI within 3 days of randomization. The overall CTO-PCI success rate was 90.6%. Serious nonfatal complications associated with CTO-PCI occurred in 3 patients (1 stroke, 1 cardiac tamponade, and 1 patient with recurrent episodes of ventricular tachyarrhythmia induced by intracoronary thrombus). Approximately half of the patients in each group underwent PCI for an average of 1.3 non-CTO lesions, resulting in a comparable residual SYNTAX score (Synergy Between PCI With TAXUS and Cardiac Surgery; 3.7±5.4 versus 4.0±5.9, P=0.42) confined to non-CTO vessels. During a median follow-up of 4.0 years (interquartile range, 2.4 to 5.1 years), there was no significant difference between the CTO-PCI and the no CTO-PCI strategies in the incidence of the primary end point (22.3% versus 22.4%, hazard ratio, 1.03; 95% CI, 0.77 to 1.37; P=0.86). Both CTO-PCI and no CTO-PCI strategy were associated with significant improvements but without between-group differences in disease-specific health status that was sustained through 36 months. CONCLUSIONS: CTO-PCI was feasible with high success rates. There was no difference in the incidence of major adverse cardiovascular events with CTO-PCI versus no CTO-PCI, but the study was limited by low power for clinical end points and high crossover rates between groups. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01078051.

OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) is highly prevalent in hospitals in many Asian countries. Recent emergence of community-associated (CA) MRSA worldwide has added another serious concern to the epidemiology of S. aureus infections. To understand the changing epidemiology of S. aureus infections in Asian countries, we performed a prospective, multinational surveillance study with molecular typing analysis. METHODS: We evaluated the prevalence of methicillin resistance in S. aureus isolates in CA and healthcare-associated (HA) infections, and performed molecular characterization and antimicrobial susceptibility tests of MRSA isolates. RESULTS: MRSA accounted for 25.5% of CA S. aureus infections and 67.4% of HA infections. Predominant clones of CA-MRSA isolates were ST59-MRSA-SCCmec type IV-spa type t437, ST30-MRSA-SCCmec type IV-spa type t019 and ST72-MRSA-SCCmec type IV-spa type t324. Previously established nosocomial MRSA strains including sequence type (ST) 239 and ST5 clones were found among CA-MRSA isolates from patients without any risk factors for HA-MRSA infection. CA-MRSA clones such as ST59, ST30 and ST72 were also isolated from patients with HA infections. CONCLUSIONS: Our findings confirmed that MRSA infections in the community have been increasing in Asian countries. Data also suggest that various MRSA clones have spread between the community and hospitals as well as between countries.