Chungnam National University Hospital

<h3>Importance</h3> Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data. <h3>Objective</h3> To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning. <h3>Evidence Review</h3> We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence. <h3>Findings</h3> In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572 000 deaths and 15.2 million DALYs), and stomach cancer (542 000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819 000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601 000 deaths and 17.4 million DALYs), TBL cancer (596 000 deaths and 12.6 million DALYs), and colorectal cancer (414 000 deaths and 8.3 million DALYs). <h3>Conclusions and Relevance</h3> The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care.

Despite the recent attention focused on the roles of the nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome in the pathogenesis of type 2 diabetes, little is known about the ex vivo profile of inflammasome activation in type 2 diabetic patients. In this study, we investigated patterns of NLRP3 inflammasome activation in monocyte-derived macrophages (MDMs) from drug-naïve patients with newly diagnosed type 2 diabetes. Type 2 diabetic subjects had significantly increased mRNA and protein expression of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), and proinflammatory cytokines in MDMs cultured with autologous sera compared with healthy controls. Upregulated interleukin (IL)-1β maturation, IL-18 secretion, and caspase-1 cleavage were observed in MDMs from type 2 diabetic patients after stimulation with various danger molecules (ATP, high-mobility group protein B1, free fatty acids, islet amyloid polypeptide, and monosodium uric acid crystals). Mitochondrial reactive oxygen species and NLRP3 were required for IL-1β synthesis in MDMs. Finally, 2 months of therapy with the antidiabetic drug metformin significantly inhibited the maturation of IL-1β in MDMs from patients with type 2 diabetes through AMP-activated protein kinase (AMPK) activation. Taken together, these data suggest that NLRP3 inflammasome activation is elevated in myeloid cells from type 2 diabetic patients and that antidiabetic treatment with metformin contributes to modulation of inflammasome activation in type 2 diabetes.

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.

OBJECTIVE: To determine the safety of laparoscopy-assisted distal gastrectomy (LADG) compared with open distal gastrectomy (ODG) in patients with clinical stage I gastric cancer in Korea. BACKGROUND: There is still a lack of large-scale, multicenter randomized trials regarding the safety of LADG. METHODS: A large-scale, phase 3, multicenter, prospective randomized controlled trial was conducted. The primary end point was 5-year overall survival. Morbidity within 30 postoperative days and surgical mortality were compared to evaluate the safety of LADG as a secondary end point RESULTS: : A total of 1416 patients were randomly assigned to the LADG group (n = 705) or the ODG group (n = 711) between February 1, 2006, and August 31, 2010, and 1384 patients were analyzed for modified intention-to-treat analysis (ITT) and 1256 were eligible for per protocol (PP) analysis (644 and 612, respectively). In the PP analysis, 6 patients (0.9%) needed open conversion in the LADG group. The overall complication rate was significantly lower in the LADG group (LADG vs ODG; 13.0% vs 19.9%, P = 0.001). In detail, the wound complication rate of the LADG group was significantly lower than that of the ODG group (3.1% vs 7.7%, P < 0.001). The major intra-abdominal complication (7.6% vs 10.3%, P = 0.095) and mortality rates (0.6% vs 0.3%, P = 0.687) were similar between the 2 groups. Modified ITT analysis showed similar results with PP analysis. CONCLUSIONS: LADG for patients with clinical stage I gastric cancer is safe and has a benefit of lower occurrence of wound complication compared with conventional ODG.

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.

BACKGROUND: Although intravascular ultrasound (IVUS) guidance has been useful in stenting for unprotected left main coronary artery stenosis, its impact on long-term mortality is still unclear. METHODS AND RESULTS: In the MAIN-COMPARE registry, patients with unprotected left main coronary artery stenosis in a hemodynamically stable condition underwent elective stenting under the guidance of IVUS (756 patients) or conventional angiography (219 patients). Patients with acute myocardial infarction were excluded. The 3-year outcomes between the 2 groups were primarily compared using propensity-score matching in the entire and separate populations according to stent type. In 201 matched pairs of the overall population, there was a tendency of lower risk of 3-year morality with IVUS guidance compared with angiography guidance (6.0% versus 13.6%, log-rank P=0.063; hazard ratio, 0.54; 95% CI, 0.28 to 1.03; Cox-model P=0.061). In particular, in 145 matched pairs of patients receiving drug-eluting stent, the 3-year incidence of mortality was lower with IVUS guidance as compared with angiography guidance (4.7% versus 16.0%, log-rank P=0.048; hazard ratio, 0.39; 95% CI, 0.15 to 1.02; Cox model P=0.055). In contrast, the use of IVUS guidance did not reduce the risk of mortality in 47 matched pairs of patients receiving bare-metal stent (8.6% versus 10.8%, log-rank P=0.35; hazard ratio, 0.59; 95% CI, 0.18 to 1.91; Cox model P=0.38). The risk of myocardial infarction or target vessel revascularization was not associated with the use of IVUS guidance. CONCLUSIONS: Elective stenting with IVUS guidance, especially in the placement of drug-eluting stent, may reduce the long-term mortality rate for unprotected left main coronary artery stenosis when compared with conventional angiography guidance.

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).

IMPORTANCE: Laparoscopic distal gastrectomy is gaining popularity over open distal gastrectomy for gastric cancer because of better early postoperative outcomes. However, to our knowledge, no studies have proved whether laparoscopic distal gastrectomy is oncologically equivalent to open distal gastrectomy. OBJECTIVE: To examine whether the long-term survival among patients with stage I gastric cancer undergoing laparoscopic distal gastrectomy is noninferior to that among patients undergoing open distal gastrectomy. DESIGN: The Korean Laparoendoscopic Gastrointestinal Surgery Study (KLASS) group, which includes 15 surgeons from 13 institutes, conducted a phase 3, multicenter, open-label, noninferiority, prospective randomized clinical trial (KLASS-01) of patients with histologically proven, preoperative clinical stage I gastric adenocarcinoma from January 5, 2006, to August 23, 2010. Survival and recurrence status of the patients was determined in December 2016. INTERVENTIONS: Patients were randomly assigned (1:1) to laparoscopic distal gastrectomy (n = 705) or open distal gastrectomy (n = 711). Of these patients, 85 received a surgical approach opposite the one to which they were randomized (63 randomized to the open surgery group and 22 to the laparoscopic group). MAIN OUTCOMES AND MEASURES: Difference in 5-year overall survival between the laparoscopic and open distal gastrectomy groups. The noninferiority margin was prespecified as -5% (corresponding hazard ratio of 1.54), with an assumed survival of 90% after 5 years in the open surgery group. RESULTS: Among the 1416 patients (mean [SD] age, 57.3 [11.1] years; 940 [66.4%] male) included in the study, the 5-year overall survival rates were 94.2% in the laparoscopic group and 93.3% in the open surgery group (log-rank P = .64). Intention-to-treat analysis confirmed the noninferiority of the laparoscopic approach compared with the open approach (difference, 0.9 percentage points; 1-sided 97.5% CI, -1.6 to infinity). The 5-year cancer-specific survival rates were similar between the 2 groups (97.1% in the laparoscopic group and 97.2% in the open surgery group, log-rank P = .91; difference, -0.03 percentage points; 1-sided 97.5% CI, -1.8 to infinity). Per-protocol analysis results were consistent with the intention-to-treat results for overall and cancer-specific survival rates. CONCLUSIONS AND RELEVANCE: The KLASS-01 trial revealed similar overall and cancer-specific survival rates between patients receiving laparoscopic and open distal gastrectomy. Laparoscopic distal gastrectomy is an oncologically safe alternative to open surgery for stage I gastric cancer. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00452751.

BACKGROUND: Several studies have compared the treatment effects of coronary stenting and coronary-artery bypass grafting (CABG). However, there are limited data regarding the long-term outcomes of these two interventions for patients with unprotected left main coronary artery disease. METHODS: We evaluated 1102 patients with unprotected left main coronary artery disease who underwent stent implantation and 1138 patients who underwent CABG in Korea between January 2000 and June 2006. We compared adverse outcomes (death; a composite outcome of death, Q-wave myocardial infarction, or stroke; and target-vessel revascularization) with the use of propensity-score matching in the overall cohort and in separate subgroups according to type of stent. RESULTS: In the overall matched cohort, there was no significant difference between the stenting and CABG groups in the risk of death (hazard ratio for the stenting group, 1.18; 95% confidence interval [CI], 0.77 to 1.80) or the risk of the composite outcome (hazard ratio for the stenting group, 1.10; 95% CI, 0.75 to 1.62). The rates of target-vessel revascularization were significantly higher in the group that received stents than in the group that underwent CABG (hazard ratio, 4.76; 95% CI, 2.80 to 8.11). Comparisons of the group that received bare-metal stents with the group that underwent CABG and of the group that received drug-eluting stents with the group that underwent CABG produced similar results, although there was a trend toward higher rates of death and the composite end point in the group that received drug-eluting stents. CONCLUSIONS: In a cohort of patients with unprotected left main coronary artery disease, we found no significant difference in rates of death or of the composite end point of death, Q-wave myocardial infarction, or stroke between patients receiving stents and those undergoing CABG. However, stenting, even with drug-eluting stents, was associated with higher rates of target-vessel revascularization than was CABG.

The triglyceride glucose (TyG) index, a product of triglyceride and fasting glucose, is a reliable marker for insulin resistance (IR). Obesity is also known to be closely related with IR. Recently, the efficiency of TyG-related markers that combine obesity markers with TyG index has been studied; however, earlier studies were limited in number and the results were inconsistent. Therefore, in this study, we investigated the efficiency of several combinations of TyG index and obesity indices, namely, body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR), in reflecting IR. Data were obtained from the Korean National Health and Nutrition Examination Survey from 2007-2010. A total of 11,149 subjects (4,777 men and 6,372 women) were included. IR was defined as the homeostasis model assessment for IR (HOMA-IR) of above the 75th percentile for each gender. Logistic regression analysis was performed after adjusting for confounding factors, to compare and identify the associations of the 4 parameters (TyG index, TyG-BMI, TyG-WC, and TyG-WHtR) with IR. For each parameter, odds ratios (OR) and 95% confidence intervals (CIs) of quartiles 2-4 were calculated and compared with quartile 1 as a reference. A receiver operating characteristic (ROC) curve analysis was conducted to evaluate the ability of each parameter to predict IR. The adjusted ORs of quartile 4 in comparison with quartile 1 (95% CIs) for IR were 7.60 (6.52-8.87) for TyG index, 12.82 (10.89-15.10) for TyG-BMI, 16.29 (13.70-19.38) for TyG-WC, and 14.86 (12.53-17.62) for TyG-WHtR. The areas under the ROC curve for each parameter were 0.690 for TyG index, 0.748 for TyG-BMI, 0.731 for TyG-WC, and 0.733 for TyG-WHtR. In conclusion, TyG-BMI was found to be superior to other parameters for IR prediction. We propose TyG-BMI as an alternative marker for assessing IR in clinical settings.

IMPORTANCE: Airflow obstruction on spirometry is universally used to define chronic obstructive pulmonary disease (COPD), and current or former smokers without airflow obstruction may assume that they are disease free. OBJECTIVE: To identify clinical and radiologic evidence of smoking-related disease in a cohort of current and former smokers who did not meet spirometric criteria for COPD, for whom we adopted the discarded label of Global Initiative for Obstructive Lung Disease (GOLD) 0. DESIGN, SETTING, AND PARTICIPANTS: Individuals from the Genetic Epidemiology of COPD (COPDGene) cross-sectional observational study completed spirometry, chest computed tomography (CT) scans, a 6-minute walk, and questionnaires. Participants were recruited from local communities at 21 sites across the United States. The GOLD 0 group (n = 4388) (ratio of forced expiratory volume in the first second of expiration [FEV1] to forced vital capacity >0.7 and FEV1 ≥80% predicted) from the COPDGene study was compared with a GOLD 1 group (n = 794), COPD groups (n = 3690), and a group of never smokers (n = 108). Recruitment began in January 2008 and ended in July 2011. MAIN OUTCOMES AND MEASURES: Physical function impairments, respiratory symptoms, CT abnormalities, use of respiratory medications, and reduced respiratory-specific quality of life. RESULTS: One or more respiratory-related impairments were found in 54.1% (2375 of 4388) of the GOLD 0 group. The GOLD 0 group had worse quality of life (mean [SD] St George's Respiratory Questionnaire total score, 17.0 [18.0] vs 3.8 [6.8] for the never smokers; P < .001) and a lower 6-minute walk distance, and 42.3% (127 of 300) of the GOLD 0 group had CT evidence of emphysema or airway thickening. The FEV1 percent predicted distribution and mean for the GOLD 0 group were lower but still within the normal range for the population. Current smoking was associated with more respiratory symptoms, but former smokers had greater emphysema and gas trapping. Advancing age was associated with smoking cessation and with more CT findings of disease. Individuals with respiratory impairments were more likely to use respiratory medications, and the use of these medications was associated with worse disease. CONCLUSIONS AND RELEVANCE: Lung disease and impairments were common in smokers without spirometric COPD. Based on these results, we project that there are 35 million current and former smokers older than 55 years in the United States who may have unrecognized disease or impairment. The effect of chronic smoking on the lungs and the individual is substantially underestimated when using spirometry alone.

RATIONALE: Bone marrow (BM)-derived mesenchymal stem cells (MSCs) hold great promise for cardiovascular cell therapy owing to their multipotency and culture expandability. OBJECTIVE: The aim of the study was to investigate whether MSCs can treat experimental acute myocardial infarction (MI) and diabetic neuropathy. METHODS AND RESULTS: We isolated mononuclear cells from mouse BM and cultured MSCs in a conventional manner. Flow cytometry analyses of these cultured cells at passage 4 showed expression of typical MSC markers such as CD44 and CD29, but not hematopoietic markers such as c-kit, flk1, and CD34. To determine the therapeutic effects of MSCs, we injected MSCs into the peri-infarct area after ligation of the left anterior descending coronary arteries of mice and, as separate experiments, injected the same batch of MSCs into hindlimb muscles of mice with diabetic neuropathy. During the follow-up at 4 to 8 weeks after cell transplantation, growing tumors were observed in 30% of hearts in the MI model, and in 46% of hindlimbs in the diabetic neuropathy model. Histological examination of the tumors revealed hypercelluarity, pleomorphic nucleoli, cytological atypia and necrosis, and positive staining for α-smooth muscle actin, indicative of malignant sarcoma with myogenic differentiation. Chromosomal analysis of these MSCs showed multiple chromosomal aberrations including fusion, fragmentation, and ring formation. CONCLUSIONS: Genetically unmodified MSCs can undergo chromosomal abnormalities even at early passages and form malignant tumors when transplanted in vivo. These results suggest that careful monitoring of chromosomal status is warranted when in vitro expanded MSCs are used for cell therapy such as for MI.

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.

PURPOSE Adjuvant chemotherapy after D2 gastrectomy is standard for resectable locally advanced gastric cancer (LAGC) in Asia. Based on positive findings for perioperative chemotherapy in European phase III studies, the phase III PRODIGY study (ClinicalTrials.gov identifier: NCT01515748 ) investigated whether neoadjuvant docetaxel, oxaliplatin, and S-1 (DOS) followed by surgery and adjuvant S-1 could improve outcomes versus standard treatment in Korean patients with resectable LAGC. PATIENTS AND METHODS Patients 20-75 years of age, with Eastern Cooperative Oncology Group performance status 0-1, and with histologically confirmed primary gastric or gastroesophageal junction adenocarcinoma (clinical TNM staging: T2-3N+ or T4Nany) were randomly assigned to D2 surgery followed by adjuvant S-1 (40-60 mg orally twice a day, days 1-28 every 6 weeks for eight cycles; SC group) or neoadjuvant DOS (docetaxel 50 mg/m 2 , oxaliplatin 100 mg/m 2 intravenously day 1, S-1 40 mg/m 2 orally twice a day, days 1-14 every 3 weeks for three cycles) before D2 surgery, followed by adjuvant S-1 (CSC group). The primary objective was progression-free survival (PFS) with CSC versus SC. Two sensitivity analyses were performed: intent-to-treat and landmark PFS analysis. RESULTS Between January 18, 2012, and January 2, 2017, 266 patients were randomly assigned to CSC and 264 to SC at 18 Korean study sites; 238 and 246 patients, respectively, were treated (full analysis set). Follow-up was ongoing in 176 patients at data cutoff (January 21, 2019; median follow-up 38.6 months [interquartile range, 23.5-62.1]). CSC improved PFS versus SC (adjusted hazard ratio, 0.70; 95% CI, 0.52 to 0.95; stratified log-rank P = .023). Sensitivity analyses confirmed these findings. Treatments were well tolerated. Two grade 5 adverse events (febrile neutropenia and dyspnea) occurred during neoadjuvant treatment. CONCLUSION PRODIGY showed that neoadjuvant DOS chemotherapy, as part of perioperative chemotherapy, is effective and tolerable in Korean patients with LAGC.

We report that vertically aligned ZnO nanowire arrays (ZnO NWAs) were fabricated on 3D graphene foam (GF) and used to selectively detect uric acid (UA), dopamine (DA), and ascorbic acid (AA) by a differential pulse voltammetry method. The optimized ZnO NWA/GF electrode provided a high surface area and high selectivity with a detection limit of 1 nM for UA and DA. The high selectivity in the oxidation potential was explained by the gap difference between the lowest unoccupied and highest occupied molecular orbitals of a biomolecule for a set of given electrodes. This method was further used to detect UA levels in the serum of patients with Parkinson's disease (PD). The UA level was 25% lower in PD patients than in healthy individuals. This finding strongly implies that UA can be used as a biomarker for PD.

BACKGROUND AND PURPOSE: The aim of this study was to investigate differences in risk factors and stroke mechanisms between intracranial atherosclerosis (ICAS) and extracranial atherosclerosis (ECAS) and between anterior and posterior circulation atherosclerosis. METHODS: A multicenter, prospective, Web-based registry was performed on atherosclerotic strokes using diffusionweighted magnetic resonance imaging and magnetic resonance angiography. Stroke mechanisms were categorized as artery-to-artery embolism, in situ thrombo-occlusion, local branch occlusion, or hemodynamic impairment. RESULTS: Onethousand patients were enrolled from 9 university hospitals. Age (odds ratio [OR], 1.033; 95% confidence interval [CI], 1.018-1.049), male gender (OR, 3.399; 95% CI, 2.335-4.949), and hyperlipidemia (OR, 1.502; 95% CI, 1.117-2.018) were factors favoring ECAS (vs ICAS), whereas hypertension (OR, 1.826; 95% CI, 1.274-2.618; P=0.001) and diabetes mellitus (OR, 1.490; 95% CI, 1.105-2.010; P=0.009) were related to posterior (vs anterior) circulation diseases. Metabolic syndrome was a factor related to ICAS (vs ECAS) only in posterior circulation strokes (OR, 2.433; 95% CI, 1.005-5.890; P=0.007). Stroke mechanisms included arterytoartery embolism (59.7%), local branch occlusion (14.9%), in situ thrombo-occlusion (13.7%), hemodynamic impairment (0.9%), and mixed (10.8%). Anterior ICAS was more often associated with artery-to-artery embolism (51.8% vs 34.0%) and less often associated with local branch occlusion (12.3% vs 40.4%) than posterior ICAS (P<0.001). CONCLUSIONS: The prevalence of risk factors and stroke mechanisms differ between ICAS and ECAS, and between anterior and posterior circulation atherosclerosis. Posterior ICAS seems to be closely associated with metabolic derangement and local branch occlusion. Prevention and management strategies may have to consider these differences.

The roles of adipokines, proinflammatory cytokines, and adipose tissue macrophages in obesity-associated insulin resistance have been explored in both animal and human studies. However, our current understanding of obesity-associated insulin resistance relies on studies of artificial metabolic extremes. The purpose of this study was to explore the roles of adipokines, proinflammatory cytokines, and adipose tissue macrophages in human patients with modest obesity and early metabolic dysfunction. We obtained omental adipose tissue and fasting blood samples from 51 females undergoing gynecologic surgery. We investigated serum concentrations of proinflammatory cytokines and adipokines as well as the mRNA expression of proinflammatory and macrophage phenotype markers in visceral adipose tissue using ELISA and quantitative RT-PCR. We measured adipose tissue inflammation and macrophage infiltration using immunohistochemical analysis. Serum levels of adiponectin and leptin were significantly correlated with HOMA-IR and body mass index. The levels of expression of MCP-1 and TNF-α in visceral adipose tissue were also higher in the obese group (body mass index ≥ 25). The expression of mRNA MCP-1 in visceral adipose tissue was positively correlated with body mass index (r = 0.428, p = 0.037) but not with HOMA-IR, whereas TNF-α in visceral adipose tissue was correlated with HOMA-IR (r = 0.462, p = 0.035) but not with body mass index. There was no obvious change in macrophage phenotype or macrophage infiltration in patients with modest obesity or early metabolic dysfunction. Expression of mRNA CD163/CD68 was significantly related to mitochondrial-associated genes and serum inflammatory cytokine levels of resistin and leptin. These results suggest that changes in the production of inflammatory biomolecules precede increased immune cell infiltration and induction of a macrophage phenotype switch in visceral adipose tissue. Furthermore, serum resistin and leptin have specific roles in the regulation of adipose tissue macrophages in patients with modest obesity or early metabolic dysfunction.

The Korea National Health and Nutrition Examination Survey (KNHANES) was initiated in 1998 to provide evidence for the development and evaluation of health policies and programs. The Korea Disease Control and Prevention Agency is responsible for the KNHANES and has conducted it as a series of surveys. Over the past 20 years, efforts to produce accurate, timely, and nationwide health statistics have been refined by establishing a continuous annual survey system with full-time field staff, incrementally expanding survey components, collaborating with relevant academic societies for quality control, and revising the survey methods. Additionally, the utility of the collected data was increased by linking the KNHANES data with related data from other government agencies or institutions and making the overall data publicly available on the official website of KNHANES (https://knhanes.kdca.go.kr). Additional long-term plans are being developed, including plans to continue producing nationwide health indicators and invigorating the utilization of the KNHANES data.

OBJECTIVE: We developed a Korean version of Mini-Mental Status Examination (MMSE) optimized for screening dementia (MMSE-DS) and its' short form (SMMSE-DS). METHODS: We constructed the MMSE-DS using the items of the two current Korean versions of MMSE and then construct the SMMSE-DS consisted of 13 items from the MMSE-DS based on the diagnostic accuracy of individual items for dementia. We investigated reliability and validity of MMSE-DS and SMMSE-DS on 1,555 subjects (1,222 nondemented controls, 333 dementia patients). We compared the diagnostic accuracy of the SMMSE-DS with that of the three full Korean versions of MMSE, and examined its' age- and education-specific optimal cutoff scores for dementia. RESULTS: The internal consistency obtained by Cronbach's coefficient alpha was 0.826. The inter-rater reliability and test-retest reliability were 0.968 (p<0.001) and 0.825 (p<0.001), respectively. It showed significant correlation with the Clinical Dementia Rating (CDR) (r=-0.698, p<0.05) and the three full Korean versions of MMSE (r=0.839-0.938, p<0.001). The area under the receiver operator curve for dementia of the SMMSE-DS was larger than those of the three full Korean versions of MMSE (p<0.001). Age, education and gender explained 19.4% of the total variance of SMMSE-DS scores. The optimal cutoff scores for dementia of the SMMSE-DS were estimated differently by age and educational attainment of the subjects. CONCLUSION: The SMMSE-DS was found to be accurate, brief and portable instrument for screening dementia in Korean elders, and may be particularly useful for screening dementia in elderly populations with wide variation in educational levels.