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Background The influence of intensive glucose control in diabetic patients on the macrovascular outcomes is controversial. Thus, this study aimed to elucidate the effect of preprocedural hemoglobin A1c (HbA1c) on clinical outcomes after endovascular therapy for lower extremity artery disease (LEAD) in diabetic patients. Methods Diabetic patients were enrolled from the retrospective cohorts of a Korean multicenter endovascular therapy registry and were divided according to the HbA1c level during index admission into the optimal ( Results Of the 1103 patients enrolled (897 men, mean age 68.2 ± 8.9 years), 432 (39.2%) were classified into the optimal glycemic control group and 671 (60.8%) into the suboptimal glycemic control group. In-hospital events and immediate procedural complications were not different between the two groups. The suboptimal group showed a trend towards a higher incidence of MALE than the optimal group (log-rank p = 0.072). Although no significant differences were found between the two groups in terms of overall survival or amputation, the risk of reintervention was significantly higher in the suboptimal group (log-rank p = 0.048). In the multivariate Cox regression model, suboptimal glycemic control was one of the independent predictors for reintervention. When our data were analyzed according to the initial presentation, suboptimal preprocedural HbA1c significantly increased the incidence of MALE compared with optimal preprocedural HbA1c only in patients with intermittent claudication. Conclusion In diabetic patients undergoing endovascular therapy for LEAD, suboptimal preprocedural HbA1c is associated with an increased risk of adverse limb events, especially in patients with intermittent claudication. Further prospective research will be required to validate the role of more intensive glycemic control on the reduction of adverse limb events in diabetic patients undergoing endovascular therapy for LEAD.

Background The Korean Society of Hypertension (KSH) revised the local guidelines for hypertension in 2018. The present study sought to evaluate the potential impact of the 2018 KSH guidelines on hypertension management status among the Korean population in terms of prevalence of hypertension, antihypertensive medical treatment recommendations, and control status in Korean adults. Methods We used data from the Korea National Health and Nutrition Examination Survey to estimate the number and percentage of Korean adults who have hypertension according to blood pressure (BP) classification, are recommended to receive antihypertensive medical treatment, and are receiving medical treatment and have BP in the optimal range according to the new recommendations. Adults aged 30 years or older who participated in the survey between 2013 and 2015 were selected for this study. Results The prevalence of hypertension was 30.5% among Korean adults aged 30 years or older. The percentage of subjects who are recommended to be treated with antihypertensive medications substantially increased from 32.5 to 37.8%, which translates to 1.6 million adults. Among the hypertensive patients who were receiving medical treatment, 38.6% were shown to have adequate BP levels as recommended by the 2018 KSH guidelines compared with 51.8% according to the previous 2013 guidelines. Conclusions The present study reports the potential impact of the 2018 KSH guidelines on the prevalence of hypertension, antihypertensive medical treatment recommendations, and control status for Korean adults. The 2018 KSH guidelines recommend more intensive BP control compared with previous guidelines. This study suggests that there is large scope for improvement in hypertension management in the Korean population.

Background Detection of arrhythmias is crucial for the treatment of cardiovascular diseases. However, conventional devices do not provide sufficient diagnostic accuracy while patients should suffer from bothersome diagnostic process. We sought to evaluate diagnostic capability and safety of the new adhesive electrocardiogram (ECG) monitoring device in patients who need ECG monitoring during admission. Methods We enrolled 10 patients who admitted to Seoul National University Bundang Hospital and required continuous ECG monitoring between October 31, 2019 and December 18, 2019. New adhesive ECG monitoring device and conventional ECG monitoring device were simultaneously applied to the patients and maintained for 48 hours. From each patient, 48 pairs of ECG signal were collected and analyzed by two cardiologists independently. Discrepancy of diagnosis and frequency of noise or signal loss were compared between the two devices. Results From analyzable ECG data, discrepancy of arrhythmia diagnosis was not observed between the two devices. Noise rate was higher in conventional ECG monitoring device (2.5% vs. 17.3%, P < 0.001) and signal loss was not observed in new adhesive device while there was 9.4% of signal losses in conventional Holter recorder group. The new device was well-tolerated among 48 hours of monitoring period and no adverse event was observed. Conclusion A newer adhesive ECG monitoring device demonstrated similar diagnostic accuracy compared to conventional ECG monitoring device., Graphical Abstract

Limited data are available regarding long-term clinical outcomes of iliac artery endovascular therapy (EVT) in real-world practice. This study investigated long-term outcomes according to Trans-Atlantic Inter-Society Consensus (TASC) classifications.We analyzed data from 1,705 limbs of 1,364 patients from the retrospective cohort of the multicenter Korean Vascular Intervention Society Endovascular Therapy in Lower Limb Artery Disease registry. The primary endpoint was target lesion revascularization (TLR)-free survival.TASC A, B, C, and D lesions were present in 19.4%, 26.2%, 28.7%, and 25.7% of the treated limbs, respectively. The technical success rate was 96.2% and did not differ between TASC lesion types. Complications occurred in 6.8% of cases and more occurred in TASC D (11.8%). Iliac artery EVT showed a 5-year TLR-free survival of 89.2%. The TASC D group had the lowest TLR-free rate of 79.3%. TASC D (hazard ratio [HR], 1.75; 95% confidence interval [CI], 1.12-2.73; p=0.014), plain old balloon angioplasty (HR, 4.25; 95% CI, 2.03-8.88; p0.001), current smoker (HR, 1.89; 95% CI, 1.26-2.83; p=0.002), previous bypass surgery (HR, 3.04; 95% CI, 1.28-7.19; p=0.011), combined femoropopliteal treatment (HR, 4.89; 95% CI, 3.19-7.50; p0.001), combined below the knee treatment (HR, 2.20; 95% CI, 1.25-3.89; p=0.007), and complications (HR, 1.86; 95% CI, 1.07-3.24; p=0.028) were predictors for TLR.Iliac artery EVT achieved excellent technical success and 5-year TLR-free survival. TASC D showed a favorable but lower 5-year TLR-free survival rate and higher complication rate compared with other TASC groups.ClinicalTrials.gov Identifier: NCT02748226.

Data pertaining to the prognostic value of the combination of high neutrophil-to-lymphocyte ratio (NLR) and anemia on admission in patients with ST-segment elevation myocardial infarction (STEMI) are limited. The objective of this study was to investigate the clinical value of baseline NLR in combination with anemia in predicting clinical outcomes after STEMI.A total of 5,194 consecutive patients with STEMI within 12 hours of symptom onset from the Korea Acute Myocardial Infarction Registry-National Institute of Health database between 2011 and 2015 were categorized into 4 groups according to their NLR and hemoglobin levels: low NLR (4) without anemia (n=2,722; reference group); high NLR (≥4) without anemia (n=1,527); low NLR with anemia (n=508); and high NLR with anemia (n=437). The co-primary outcomes were 180-day and 3-year all-cause mortality.Mortality rates significantly increased at the 3-year follow-up across the groups (3.3% vs. 5.4% vs. 16.5% vs. 21.7% for 180-day mortality and 5.3% vs. 9.0% vs. 23.8% vs. 33.4% for 3-year mortality; allThis nationwide prospective cohort study showed that the combination of high NLR (≥4) and anemia is a strong predictor of all-cause mortality after STEMI.

Endovascular therapy (EVT) first strategy has been widely adopted for the treatment of chronic limb threatening ischemia (CLTI) patients in real-world practice. This study aimed to investigate long-term outcomes of CLTI patients who underwent EVT and identify prognostic factors.From the retrospective cohorts of a Korean multicenter endovascular therapy registry, 1,036 patients with CLTI (792 men, 68.8 ± 9.5 years) were included. The primary endpoint was amputation-free survival (AFS) defined as the absence of major amputation or death. Secondary endpoints were major adverse limb events (MALE; a composite of major amputation, minor amputation, and reintervention).Five-year AFS and freedom from MALE were 69.8% and 61%, respectively. After multivariate analysis, age (hazard ratio [HR], 1.476; p0.001), end-stage renal disease (ESRD; HR, 2.340; p0.001), Rutherford category (RC) 6 (HR, 1.456; p=0.036), and suboptimal EVT (HR, 1.798; p=0.005) were identified as predictors of major amputation or death, whereas smoking (HR, 0.594; p=0.007) was protective. Low body mass index (HR, 1.505; p=0.046), ESRD (HR, 1.648; p=0.001), femoropopliteal lesion (HR, 1.877; p=0.004), RC-6 (HR, 1.471; p=0.008), and suboptimal EVT (HR, 1.847; p=0.001) were predictors of MALE. The highest hazard rates were observed during the first 6 months for both major amputation or death and MALE. After that, the hazard rate decreased and rose again after 3-4 years.In CLTI patients, long-term outcomes of EVT were acceptable. ESRD, RC-6, and suboptimal EVT were common predictors for poor clinical outcomes.ClinicalTrials.gov Identifier: NCT02748226.

To compare the safety and efficacy of a new everolimus-eluting stent with an abluminal-coated biodegradable polymer (Osstem Cardiotec Centum) with those of the Xience Alpine stent (Xience).This randomized, prospective, multicenter, parallel-designed, single-blind trial was conducted among patients with myocardial ischemia undergoing percutaneous coronary intervention (PCI) from 21st September 2018 until 3rd July 2020. The primary efficacy endpoint was in-segment late lumen loss (LLL) at 270 days after the procedure and the primary safety endpoints were major adverse cardiac events (MACE), composite of cardiac death, myocardial infarction, and target lesion revascularization.We enrolled 121 patients and analyzed 113 patients who finished 270 days of follow-up for the primary efficacy endpoint. The mean age of the participants was 66.8 years. As for the primary efficacy endpoint, LLL of the Osstem Cardiotec Centum group was 0.09±0.13 mm and that of the Xience group was 0.12±0.14 mm (upper limit of 1-sided 95% confidence interval, 0.02; p for non-inferiority, 0.0084). This result demonstrates the non-inferiority of the Osstem Cardiotec Centum. As for the primary safety endpoint, MACE occurred in one patient (1.59% of the Xience group). Meanwhile, no MACE occurred in the Osstem Cardiotec Centum group.The Osstem Cardiotec Centum is non-inferior to the Xience Alpine® stent and is confirmed to be safe. It could be safely and effectively applied to patients with coronary artery disease undergoing PCI.

The aim of this study was to compare gastric cancer (GC) patients aged 80 years or older undergoing gastrectomy at two high-volume cancer centers in the US and China. Patients aged ≥ 80 years who underwent R0 resection at Memorial Sloan Kettering Cancer Center (MSKCC) in New York, USA (n = 159), and Fujian Medical University Union Hospital (FMUUH) in Fujian, China (n = 118) from January 2000 to December 2013 were included. Demographic, surgical, and pathologic variables were compared, and factors associated with survival were determined via multivariate analysis. The number of patients increased annually in the FMUUH cohort but not in the MSKCC cohort. Patients at MSKCC were slightly older (mean age 83.7 vs. 82.7 years), more commonly female (38 vs. 19%), and had higher average body mass index (BMI; 26 vs. 23). Treatment at FMUUH more frequently employed total gastrectomy (59 vs. 20%) and laparoscopic surgery (65 vs. 7%), and less frequently included adjuvant therapy (11 vs. 18%). In addition, FMUUH patients had larger tumors of more advanced T, N, and TNM stage. Morbidity (35 vs. 25%, p = 0.08) and 30-day mortality (2.5 vs. 3.3%, p = 0.67) were similar between the cohorts. For each TNM stage, there was no significant difference between MSKCC and FMUUH patients in 5-year overall survival and disease-specific survival (DSS). TNM stage was the only independent predictor of DSS for both cohorts. Patients ≥ 80 years of age selected for gastrectomy for GC at MSKCC and FMUUH had acceptable morbidity and mortality, and DSS was primarily dependent on TNM stage.

The 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension guideline lowered the threshold defining hypertension and treatment target from 140/90 mmHg to 130/80 mmHg. We compared the 2017 ACC/AHA guideline and the Eighth Joint National Committee (JNC8) report with regard to the current status of hypertension using the Korean National Health and Nutrition Examination Survey. The association between blood pressure (BP) control and long-term major cardiovascular outcomes (MACEs) was analyzed using the Korea National Health Insurance Service cohort. In the cross-sectional study with 15,784 adults, the prevalence of hypertension was expected to be 49.2 ± 0.6% based on the definition suggested by the 2017 ACC/AHA guideline versus 30.4 ± 0.6% based on the JNC8 report. In a longitudinal analysis with 373,800 hypertensive adults for the median follow-up periods of 11.0 years, the adults meeting the target goal BP goal of 2017 ACC/AHA guideline were associated with 21% reduced risk of MACEs compared with adults, not meeting 2017 ACC/AHA BP goal but meeting JNC8 target goal. In conclusion, substantial increase of prevalence of hypertension is expected by the 2017 ACC/AHA guideline. This study also suggests endorsing the aggressive approach would lead to an improvement in cardiovascular care.

Structured Abstract Background Percutaneous coronary intervention (PCI) for true ostial left anterior descending artery (LAD)-chronic total occlusion (CTO) lesions poses technical challenges owing to its inherent anatomical features. Methods In total, 270 consecutive patients who underwent PCI for ostial LAD-CTO at 13 major cardiac centers in South Korea were included. Ostial LAD-CTO was strictly defined as a LAD-CTO lesion the proximal cap of which was confined within 1 mm from the carina of the distal left main coronary artery (LMCA) bifurcation. Results Ostial LAD-CTOs were frequently accompanied by stumpless lesion entry (43.4%), whereas significant bending within the occluded segment was less frequent (14.4%). The overall technical success rate was 85.9%, and serious in-hospital adverse events occurred in 5.6%. The retrograde approach tended to contribute more frequently to success in patients with concomitant LMCA disease, stumpless CTO, interventional collaterals, and higher Japanese-CTO scores. Apparent dissection or hematoma requiring rescue procedure at the LMCA or left circumflex artery occurred in 14 patients (5.2%), with a higher tendency in patients who had LMCA disease (12.1% vs. 4.2%) and stumpless entry (9.4% vs. 2.0%) than in those without. Among patients who were successfully treated with an average number of 1.7 stents, target-vessel failure occurred in 23 patients (9.9%) during a median 3.3 years of follow-up. Conclusions In this first, large-scale analysis of true ostial LAD-CTO, PCI was feasible with a high technical success rate and favorable mid-term outcomes. Clinically relevant inflow vessel injury can occur during PCI and should be an important technical consideration regarding safety.

Background: TARGIT-A trial showed that intraoperative radiotherapy (IORT) using Intrabeam® concurrent with lumpectomy within a risk-adapted approach could be considered as an option for eligible patients with early breast cancer. To introduce IORT in clinical practice for Korean breast cancer patients, safety profiles for this new technique from clinical trial with Korean are required due to ethnic (anatomical) difference. Acute toxicity is a key hurdle for patients receiving IORT, because IORT may affect wound healing and increase wound complications. We conducted a phase II study as a feasibility test of IORT at the dose of 20 Gy for the replacement of boost-EBRT in Korean women who are candidates for breast-conserving treatment. Methods: This single-arm trial aimed to investigate acute toxicity occurred within 6 months after IORT. In 1,119 patients receiving EBRT from TARGIT-A trial, the incidence of acute toxicity within 6 months is 15%. Compared with WBRT, we aim to prove a non-inferiority of IORT with 20 Gy. A sample size of 195 achieves 80% power to detect a non-inferiority proportion (P0) of 0.2300 using a one-sided binomial test for non-inferiority. These results assume that the actual proportion (P1) is 0.1500. Considering a drop-out rate of 10%, the trial would need to enroll 215 patients in total. This trial is registered with ClinicalTrials.gov, number NCT02213991. Results: From August 2014 to November 2016, 233 women with early breast cancer were screened, and 215 undergoing IORT were enrolled. In 36 women, clinically significant complications during acute period are noted. The rate of patients experiencing acute toxicity was 16.7% (95% CI, 11.8-21.7%). The actual non-inferiority margin of our trial was 21.7% under the pre-specified margin as 23.0%. In details, There are 31 with seroma collection (more than 3 times when aspiration volume is over 10cc), 2 with wound infection, and 5 with skin break down. At a median follow-up of 17.8 months, there is no local recurrence. Conclusions: Targeted intraoperative radiotherapy using Intrabeam® is a safe procedure for Korean breast cancer patients with acceptable toxicity profile in acute period. Citation Format: Lee HW, Yoon C, Ahn SG, Kim JW, Cha YJ, Lee IJ, Jeong J. A prospective phase II study of TARGeted Intraoperative radioTherapy boost plus whole breast irradiation in breast cancer patients undergoing breast-conserving treatment [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-11-21.

Pluripotent stem cell (PSC) variations can cause significant differences in the efficiency of cardiac differentiation. This process is unpredictable, as there is not an adequate indicator at the undifferentiated stage of the PSCs. We compared global gene expression profiles of two PSCs showing significant differences in cardiac differentiation potential. We identified 12 up-regulated genes related to heart development, and we found that 4 genes interacted with multiple genes. Among these genes, Gata6 is the only gene that was significantly induced at the early stage of differentiation of PSCs to cardiomyocytes. Gata6 knock-down in PSCs decreased the efficiency of cardiomyocyte production. In addition, we analyzed 6 mESC lines and 3 iPSC lines and confirmed that a positive correlation exists between Gata6 levels and efficiency of differentiation into cardiomyocytes. In conclusion, Gata6 could be utilized as a biomarker to select the best PSC lines to produce PSC-derived cardiomyocytes for therapeutic purposes. [BMB Reports 2018; 51(2): 85-91].

Background/Aims: Currently, office blood pressure (OBP) is the most widely used method of measuring blood pressure (BP) in daily clinical practice. However, data on the diagnostic accuracy of OBP in reference to ambulatory blood pressure (ABP) are scarce in Korea. Methods: In retrospective and prospective cohorts, manual OBP and ABP mea surements were compared among ambulatory hypertensive patients. Hyperten sion was defined as systolic OBP ≥ 140 mmHg and/or diastolic OBP ≥ 90 mmHg, and systolic ABP ≥ 130 mmHg and/or diastolic ABP ≥ 80 mmHg. Results: In the retrospective cohort (n = 903), the mean OBP1 (before ABP mea surement) was higher than ABP in both systolic (138 ± 17 mmHg vs. 123 ± 13 mmHg, p < 0.001) and diastolic (84 ± 12 mmHg vs. 78 ± 11 mmHg, p < 0.001) mea surements. Interestingly, there was only a weak correlation between OBP and ABP (r2 = 0.038, p < 0.001). The overall discordance rate of OBP compared to ABP, which is the reference method for measuring BP, was 43.9%. The prospective cohort (n = 57) showed similar results. In a subgroup analysis, male patients had higher false negative results (masked or under-treated hypertension) than did female patients (26.1% vs. 17.8%, p = 0.003), whereas female patients had a higher false positive rate (white-coat or over-treated hypertension) than did male patients (28.7% vs. 15.2%, p < 0.001). Conclusions: The diagnostic accuracy of manual OBP is low in reference to ABP. Men and women have different patterns of discordance. These findings indicate that management of hypertensive patients with manual OBP measurements may be suboptimal and encourages the use of ABP in ambulatory hypertensive pa tients.

Objective Chest pain is one of the most common complaints in the emergency department (ED). Cardiac computed tomography angiography (CCTA) is a frequently used tool for the early triage of patients with low- to intermediate-risk acute chest pain. We present a study protocol for a multicenter prospective randomized controlled clinical trial testing the hypothesis that a low-dose CCTA protocol using prospective electrocardiogram (ECG)-triggering and limited-scan range can provide sufficient diagnostic safety for early triage of patients with acute chest pain. Methods The trial will include 681 younger adult (aged 20 to 55) patients visiting EDs of three academic hospitals for acute chest pain or equivalent symptoms who require further evaluation to rule out acute coronary syndrome. Participants will be randomly allocated to either low-dose or conventional CCTA protocol at a 2:1 ratio. The low-dose group will undergo CCTA with prospective ECG-triggering and restricted scan range from sub-carina to heart base. The conventional protocol group will undergo CCTA with retrospective ECG-gating covering the entire chest. Patient disposition is determined based on computed tomography findings and clinical progression and all patients are followed for a month. The primary objective is to prove that the chance of experiencing any hard event within 30 days after a negative low-dose CCTA is less than 1%. The secondary objectives are comparisons of the amount of radiation exposure, ED length of stay and overall cost. Results and conclusion Our low-dose protocol is readily applicable to current multi-detector computed tomography devices. If this study proves its safety and efficacy, dose-reduction without purchasing of expensive newer devices would be possible.

Secondhand smoke exposure (SHSE) in nonsmokers has been associated with premature cardiovascular mortality and ischemic heart disease. We conducted a cross-sectional, population-based study evaluating the relationship between SHSE, measured by subjective and objective methods, and conventional cardiovascular risks such as blood pressure, lipid profiles, and fasting glucose.We extracted information on 7376 healthy adults who had never smoked, for whom there were available urine cotinine levels, from the Korea National Health and Nutrition Examination Survey 2008-2011. SHSE was defined using self-report questionnaires and urine cotinine levels. The main outcomes included SBP and DBP, serum lipid profiles, and fasting glucose.The mean age of the study population was 45.4 ± 0.4 years and 75.2% were women. Self-reported SHSE had no significant association with study outcomes except for DBP, which had marginally positive relationships (P = 0.060). Unadjusted analysis showed higher cotinine levels were associated with lower SBP, total cholesterol, LDL cholesterol, and triglyceride. All associations lost statistical significance after multivariable adjustment. Fasting glucose had a positive relationship with urine cotinine in quartiles but not with logarithm-transformed cotinine.Although SHSE is associated with increased risk of cardiovascular mortality and morbidity, we did not find any consistent relationship among SHSE and blood pressure, lipid, or fasting glucose levels in this cross-sectional study. Using objective measurements of urine cotinine did not alter this relationship. Further long-term prospective studies are needed to evaluate the effect of SHSE as a cardiovascular risk factor.

Rac1, a Rho GTPase family member, is dysregulated in a variety of tumor types including gastric adenocarcinoma, but little is known about its role in cancer stem-like cells (CSCs). Therefore, Rac1 activity and inhibition were examined in gastric adenocarcinoma cells and mouse xenograft models for epithelial-to-mesenchymal transition (EMT) and CSC phenotypes. Rac1 activity was significantly higher in spheroid-forming or CD44+ gastric adenocarcinoma CSCs compared with unselected cells. Rac1 inhibition using Rac1 shRNA or a Rac1 inhibitor (NSC23766) decreased expression of the self-renewal transcription factor, Sox-2, decreased spheroid formation by 78%–81%, and prevented tumor initiation in immunodeficient mice. Gastric adenocarcinoma CSCs had increased expression of the EMT transcription factor Slug, 4.4- to 8.3-fold greater migration, and 4.2- to 12.6-fold greater invasion than unselected cells, and these increases could be blocked completely with Rac1 inhibition. Gastric adenocarcinoma spheroid cells were resistant to 5-fluorouracil and cisplatin chemotherapy, and this chemotherapy resistance could be reversed with Rac1 shRNA or NSC23766. The PI3K/Akt pathway may be upstream of Rac1, and JNK may be downstream of Rac1. In the MKN-45 xenograft model, cisplatin inhibited tumor growth by 50%, Rac1 inhibition by 35%, and the combination by 77%. Higher Rac1 activity, in clinical specimens from gastric adenocarcinoma patients who underwent potentially curative surgery, correlated with significantly worse survival (P = 0.017). In conclusion, Rac1 promotes the EMT program in gastric adenocarcinoma and the acquisition of a CSC state. Rac1 inhibition in gastric adenocarcinoma cells blocks EMT and CSC phenotypes, and thus may prevent metastasis and augment chemotherapy. Implications: In gastric adenocarcinoma, therapeutic targeting of the Rac1 pathway may prevent or reverse EMT and CSC phenotypes that drive tumor progression, metastasis, and chemotherapy resistance. Mol Cancer Res; 15(8); 1106–16. ©2017 AACR.

Objective The pathophysiology and natural course of coronary nonculprit plaques remain unclear. We investigated whether the short-term natural course of nonculprit plaques differs between ST-segment elevation myocardial infarction (STEMI) and chronic total occlusion (CTO) patients. Methods We performed serial virtual histology intravascular ultrasound on nonculprit plaques in 26 STEMI and 11 CTO lesions at baseline and the 6-month follow-up. Results At baseline, more lesions in the STEMI group were virtual histology intravascular ultrasound-derived thin-cap fibroatheromas (TCFA; 76.9 vs. 18.1%, P=0.002). During the follow-up period, the plaque composition changed dynamically in the STEMI group (fibrofatty: 9.8±1.9 to 17.3±2.9%, P=0.030; dense calcium: 12.7±1.8 to 8.1±1.7%, P=0.026; necrotic core: 21.1±1.8 to 15.4±2.2%, P=0.052), with a consistent plaque size. In the CTO group, the plaque composition and plaque size remained consistent without a significant change. Also, more lesions in the STEMI group remained as or progressed to TCFA, compared with the CTO group (67 vs. 11%, P=0.089). Factors associated with a persistent TCFA or with a new development of TCFA were a large necrotic core volume index and the diagnosis of STEMI, whereas new statin usage was a protective factor. Conclusion Nonculprit lesions in STEMI patients were more unstable at the baseline compared with those in CTO patients. During follow-up, nonculprit lesions in STEMI and CTO patients showed a distinct pattern of change; the former were stabilized in plaque composition, whereas the latter remained consistent. The diagnosis of STEMI and a large necrotic core volume were predictors of evolution to a TCFA, and new statin usage was a protective factor.

The biological functions of circular RNAs (circRNAs) in gastric cancer (GC) remain largely unexplored. Here, we identified that circ-RanGAP1 was significantly upregulated in both GC tissues and exosomes from the plasma of GC patients. High circ-RanGAP1 expression was closely associated with an advanced TNM stage, lymph node metastases, and worse survival. Inhibition of circ-RanGAP1 decreased GC cell invasion and migration in vitro. Overexpression of circ-RanGAP1 had the opposite effect. Additionally, circ-RanGAP1 silencing remarkably suppressed tumor growth and metastasis of GC in vivo. Mechanistically, circ-RanGAP1 sponged miR-877-3p to upregulate VEGFA expression. Overexpression of miR-877-3p reversed the biological functions mediated by circ-RanGAP1 in GC cells. Interestingly, we demonstrated that circ-RanGAP1 was upregulated in plasma exosomes from preoperative GC patients. More importantly, the plasma exosomes derived from these patients enhanced the migration and invasion potential of GC cells. Overall, the circ-RanGAP1-mediated miR-877-3p/VEGFA axis promotes GC progression. Our findings suggest that circ-RanGAP1 might act as a potential prognostic biomarker and therapeutic target for GC treatment.

Background To evaluate the association between retinal artery occlusion (RAO) and subclinical coronary artery disease (CAD). Methods We studied 41 patients with non-arteritic RAO without any history or symptoms of CAD, who had undergone coronary computed tomographic angiography (CCTA) for systemic atherosclerotic evaluation between 2007 and 2012. The age- and gender-matched control group comprised 4-fold subjects who were randomly selected from asymptomatic subjects who underwent CCTA during general health evaluation. Medical records and CCTA findings were compared between RAO patients and control groups. Multiple logistic regression analysis was carried out to assess the risk factors associated with CAD. Results Cardiovascular risk factors were not significantly different between RAO patients and control groups. RAO patients showed higher coronary artery calcium score than did control subjects (267.9 ± 674.9 vs. 120.2 ± 289.5). On CCTA, the prevalence of obstructive CAD (diameter stenosis ≥ 50%) in RAO patients was significantly higher than that in controls (29% vs. 15%; odds ratio [OR], 3.0). RAO patients demonstrated a significantly higher segment-involvement score (SIS) (2.6 ± 3.0 vs. 1.6 ± 2.4) and segment-stenosis score (SSS) (3.6 ± 4.8 vs. 2.0 ± 3.3) than did controls. After adjustment of associated factors, RAO showed significant association (OR, 3.0) with obstructive CAD and extensive CAD (SIS > 4: OR, 2.8; SSS > 8: OR, 3.4). Conclusion Patients with RAO had a higher prevalence of subclinical obstructive CAD with a more extensive and heavier burden of coronary artery plaques than did age- and gender-matched controls. Physicians should understand the potential risk of CAD in RAO patients., Graphical Abstract

Background/Introduction Physical activity has been shown to reduce mortality in a dose-response fashion. Current guidelines recommend 500 to 1,000 MET-min per week of regular physical activity. However, evidence is limited regarding the specific dose-response relationship in patients with cardiovascular disease. Purpose Our aim was to compare the impact of physical activity on mortality in primary versus secondary cardiovascular prevention. Methods We analyzed 441,798 individuals with complete information on physical activity levels between 2009 and 2015 were extracted from a population-based cohort (National Health Insurance Service-National Health Screening cohort). Physical activity measured by self-report questionnaires. A rating of 2.9, 4.0, and 7.0 METs were assigned for light-intensity, moderate-intensity, and vigorous-intensity activities, respectively. Physical activity-related energy expenditure (MET-min/week) was calculated by summing the product of frequency, intensity, and duration. The level of physical activity was classified into 0, 0 to 499, 500 to 999, 1,000 to 1,499, and ≥1,500 MET-min/week. Study participants were stratified by the presence of cardiovascular disease, defined as prior myocardial infarction, ischemic heart disease, prior stroke, and/or chronic heart failure. The main study outcome was all-cause mortality. The median follow-up duration was 5.9 years. Results Individuals with cardiovascular disease had lower physical activity levels and a higher risk of mortality than those without cardiovascular disease. There was an inverse relationship between the physical activity level and the mortality risk in both groups. The benefit in the secondary prevention group was shown to be greater than that in the primary prevention group: every 500 MET-min/week increase in physical activity resulted in a 14% and 7% risk reduction in mortality in the secondary and primary prevention groups, respectively (interaction P Adjusted risk of mortality Conclusion Individuals with cardiovascular disease may benefit from physical activity to a greater extent than do healthy subjects without cardiovascular disease. Clinicians should encourage patients with cardiovascular disease to maintain a physically active lifestyle as much as possible.

This study aimed to determine the association between achieved blood pressure at 6-month follow-up and cardiovascular outcomes at 2 years in patients treated with β-blockers and renin-angiotensin-aldosterone blockers after acute myocardial infarction (AMI).We analyzed data from 5503 patients enrolled in the national AMI registry. Patients with myocardial reinfarction (MrI), rehospitalization for heart failure (rHHF), or stroke before 6-month follow-up were excluded. Achieved blood pressures were categorized into 10-mm Hg increments. The primary outcome was all-cause death. The secondary outcome was a composite of all-cause death, MrI, and rHHF. Hazard ratios (HRs) were estimated with multivariable-adjusted Cox hazards models using 125- to 134-mm Hg systolic blood pressure (SBP) and 75- to 84-mm Hg diastolic blood pressure (DBP) subgroups as reference.After a median follow-up of 2.1 years, SBP115 mm Hg was associated with increased risks for all-cause death (adjusted HR: 2.202 [1.158-4.188]) and for a composite outcome (HR: 1.682 [1.075-2.630]). Likewise, DBP75 mm Hg tended to be associated with an increase in all-cause death (HR: 2.078 [0.998-4.327] for DBP of 65 to 74 mm Hg; HR: 2.610 [1.256-5.423] for DBP65 mm Hg). Even in patients75 years, the risk of a composite outcome was increased for DBP65 mm Hg (HR: 2.492 [1.401-4.434]).Low blood pressure achieved with β-blocker and renin-angiotensin-aldosterone blocker at 6 months was associated with an increased risk of all-cause mortality independently of confounding factors in patients with AMI. This finding suggests that caution should be taken for patients with AMI who use blood-pressure-lowering treatments.

Abstract Head and neck squamous cell carcinomas (HNSCCs) harbor a subset of cells that are CD44(+) and present with malignancy and radiotherapy resistance. As a key regulator of self-renewal, Nanog expression not only determines cell fate in pluripotent cells but also mediates tumorigenesis in cancer cells; thus, we examined the role of Nanog in CD44(+) HNSCC. Three HNSCC cell lines, tumor xenografts, and patient tumors were examined. Nanog levels were significantly higher in CD44(+) HNSCC spheroids than in CD44(−) spheroids, and further increased when grown as spheroids to enrich for CSCs. CD44(+) spheroids showed a 3.4–7.5-fold increase in migration and invasion compared with CD44(−) spheroids and were resistant to radiation therapy, which was reversed by inhibiting Nanog. Nanog knockdown also decreased spheroid formation by 66.5–68.8%. Moreover, a phosphokinase array identified upregulated ERK1/2 signaling in CD44(+) HNSCC cells compared with that in CD44(−) cells. ERK1/2 signaling was found to regulate Nanog expression, aiding tumor progression, metastasis, and radiotherapy resistance. In xenograft models, the combination of radiation and Nanog or ERK1/2 inhibition inhibited tumor growth by 75.6% and 79.1%, respectively. In lung metastasis models, CD44(+) cells injected into the tail vein of mice led to significantly more lung metastases and higher Nanog expression level compared with that by ERK1/2-knockdown CD44(+) cells. Finally, in tumor tissues, CD44 and Nanog expression levels were correlated with tumorigenesis in HNSCC patients. Thus, targeting Nanog and the ERK1/2 signaling pathway may prevent or reverse CSC phenotypes and epithelial–mesenchymal transition that drive tumor progression, metastasis, and radiotherapy resistance in HNSCC.

BACKGROUND Self-expandable stents, Absolute Pro® (ABS) and Complete SE® (COM), demonstrated safety and efficacy in previous studies. We aimed to determine which stent is more effective for the endovascular treatment of femoropopliteal artery disease. METHODS We enrolled patients who underwent endovascular intervention from 2010 to 2015 in our hospital. The primary endpoint was clinical primary patency, which is a composite of freedom from restenosis or clinically driven target lesion revascularization (TLR). RESULTS A total of 197 patients and 210 limbs were analyzed, with 96 limbs of 88 patients assigned to the ABS group and 114 limbs of 109 patients assigned to the COM group. Baseline and lesion characteristics were similar between the two groups. The number of stents per limbs were 1.28±0.55 and 1.29±0.51 in the ABS and COM groups, respectively (P=0.92). The postprocedure ankle-brachial index was significantly improved in both groups compared with the preprocedural one (P

Elevated blood pressure (BP) has been proposed as a possible pathophysiological mechanism linking exposure to ambient air pollution and the increased risk of cardiovascular mortality and morbidity. In this study, we investigated the hourly relationship between ambient air pollutants and BP. BP measurements were extracted from the electronic health record database of the Seoul National University Bundang Hospital from February 2015 to June 2017. A total of 98,577 individual BP measurements were matched to the hourly levels of air pollutants. A generalized additive model was constructed for hour lags of 0–8 of air pollutants adjusting for age, sex, meteorological variables, and time trend. Systolic BP was shown to be significantly lower at 2–4 hours and 3–5 hours after increased levels of SO2 and CO, respectively (0.24 mmHg and 0.26 mmHg for an interquartile range, respectively). In contrast, O3 and NO2 were associated with significantly increased systolic BP at 3–5 lag hours and at 0–2 lag hours, respectively. BP elevation in association with O3 and NO2 was shown to be significantly greater in hypertensive patients than normotensive subjects. Our findings suggest that short-term exposure to air pollution may be associated with elevated BP.

ObjectivesTo date, no research has investigated the association between cardiac complication and electrical injury; hence, we aimed to assess the consequences and relating factors of cardiac complications from electrical injuries in South Korea.DesignRetrospective single-centre study.Participants721 patients who had electrical injury–related admission during 2007–2017. An electronic medical record system was used to extract records of patients admitted for electrical injury treatment.ResultsCardiac complications included abnormal parameters of myocardial damage, abnormal regional wall motion detected via echocardiogram, dysrhythmia (eg, bradycardia, atrial flutter/fibrillation) and ventricular tachycardia or fibrillation. Overall, 107 patients (14.8%) experienced cardiac complications. The average admission duration and intensive care unit stay duration were significantly longer in patients with cardiac complications than in those without them (75.0±45.3 vs 56.6±48.0 days and 19.3±24.1 vs 10.4±15.5 days, respectively, p=0.01). All deaths occurred within 32 days, and the most common cause of death was septic shock. Total body surface area (TBSA) was only positively related factor to cardiac complications.ConclusionThis study is the first in South Korea to reveal that electrical accident patients with cardiac complications experience poorer in-hospital prognosis, and TBSA was the only risk factor of cardiac complications. And initial treatment for infection and inflammations could be important in electrical injury.

AIMS The aim of this study was to compare the outcomes between multivessel and infarct-related artery (IRA)-only percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI), multivessel disease (MVD), and severe renal dysfunction (RD) using the nationwide AMI registry. METHODS AND RESULTS Among 13,104 patients, 537 diagnosed with AMI and MVD who had severe RD at presentation (estimated glomerular filtration rate [GFR]

Aims Physical activity has been shown to reduce mortality in a dose-response fashion. Current guidelines recommend 500–1000 metabolic equivalent task (MET)-min per week of regular physical activity. This study aimed to compare the impact of leisure-time physical activity on mortality in primary versus secondary cardiovascular prevention. Methods and results This study included a total of 131 558 and 310 240 subjects with and without cardiovascular disease (CVD), respectively, from a population-based cohort. Leisure-time physical activity was measured by self-report questionnaires. The study subjects were followed-up for a median of 5.9 years, and the main study outcome was all-cause mortality. There was an inverse relationship between the physical activity level and the mortality risk in both groups. The benefit in the secondary prevention group was shown to be greater than that in the primary prevention group: every 500 MET-min/week increase in physical activity resulted in a 14% and 7% risk reduction in mortality in the secondary and primary prevention groups, respectively (interaction P < 0.001). In addition, while individuals without CVD benefited the most between 1 and 500 MET-min/week of physical activity, the benefit in those with CVD continued above 500 − 1000 MET-min/week. The adjusted mortality risk of individuals with CVD who performed a high level of physical activity (≥1000 MET-min/week) was shown to be comparable to or lower than that of their counterparts without CVD. Conclusion Individuals with CVD may benefit from physical activity to a greater extent than do healthy subjects without CVD.

Background/aims Whether the presence of chronic total occlusion (CTO) affects patency after stenting in femoropopliteal lesions is unknown. We determined the effects of plain balloon angioplasty (POBA) in comparison with those of stenting on patency for femoropopliteal CTO and stenosis (non-CTO). Methods We analyzed data from the Korean Vascular Intervention Society Endovascular Therapy in Lower-Limb Artery Diseases Registry, a multicenter cohort of patients with lower extremity peripheral arterial disease. Data from 1,329 patients and 1558 limbs treated with endovascular intervention for at least one femoropopliteal lesion were evaluated. Results Among the 1,558 limbs, 345, 432, 275, and 506 were in the non-CTO-POBA, non-CTO-stent, CTO-POBA, and CTO-stent groups, respectively. During follow-up, loss of clinical primary patency, a composite of freedom from restenosis or clinically driven target lesion revascularization, occurred in 65 (18.8%), 68 (15.7%), 62 (22.5%), and 113 limbs (22.3%) in the non-CTO-POBA, non-CTO-stent, CTO-POBA, and CTO-stent groups, respectively. The patients in the non-CTO-stent group showed a significantly better clinical primary patency than those in the no-CTO-POBA group, whereas those in the CTO-stent and CTO-POBA groups showed no significant differences. After inverse probability of treatment weighting to balance the differences among covariates between the non-CTO-stent and non-CTO-POBA groups, the non-CTO-stent group still showed superior clinical primary patency as compared with the non-CTO-POBA group. Conclusion In the patients with femoropopliteal stenosis without CTO, stenting resulted in better clinical outcomes than balloon angioplasty. The presence of CTO in the femoropopliteal lesion should be considered when selecting a suitable device for performing endovascular procedures.

Background With advances in peripheral artery disease ( PAD ) treatments such as endovascular treatment ( EVT ), personalized patient assessment is important. Data on sex differences in clinical outcome for PAD patients undergoing EVT have been limited, and studies have produced conflicting results. This study sought to compare midterm clinical outcomes between women and men in a large population of patients with PAD undergoing EVT . Methods and Results The K‐ VIS ELLA (Korean Vascular Intervention Society Endovascular Therapy in Lower Limb Artery Disease) registry is a nationwide, multicenter, observational study that includes 3073 PAD patients undergoing EVT . The study population was divided into men (n=2523) and women (n=550). The primary outcome was a composite of death, myocardial infarction, and major amputation; the secondary outcome included major adverse limb events. Women had more comorbidities and more severe and complex target lesions than men. Women showed higher rates of death, myocardial infarction, or major amputation than men (14.8% versus 9.8%, adjusted hazard ratio 1.350, 95% CI 1.017‐1.792, P =0.038), and higher rates of major adverse limb events (19.9% versus 14.5%, adjusted hazard ratio 1.301, 95% CI 1.014‐1.670, P =0.039) and procedural complications (10.2% versus 5.9%, P CI 1.421‐3.068, P CI 0.800‐1.694, P =0.426). A significant interaction ( P =0.035) between patient presentation and outcome was observed. Conclusions In a large population of patients with PAD undergoing EVT , women had higher rates of death, myocardial infarction, or major amputation than men and higher rates of complex lesions, procedural complications, and limb‐specific adverse events.

Background Graduate medical education is shifting from the traditional apprenticeship model to a competency-driven model. Here we describe the design and implementation of competency-based medical education (CBME) in an internal medicine residency program, and report satisfaction survey results. Methods We redesigned the residency curriculum as CBME to be resident-centred, systematic, focused on general internal medicine, to provide experience in various care setting, and work-based assessment. In the second year of this CBME transition, we surveyed residents' overall satisfaction using 5-point Likert scale. Feedback on their training program was also analysed. Results The overall satisfaction score was 3.24 and thirteen residents (61.9%) answered that the preceptor's practical training in an educational atmosphere and improvement through training were the merits of the training program. However, residents complained about the working condition such as work overload. Conclusion With the CBME implementation, most residents expressed satisfaction with the hospital's educational environment but they suffered from overwork. Further efforts to improve the educational program and environment are warranted.

Background Diabetes mellitus (DM) causes macro- and microvasculopathy, but data on cardiac microvascular changes in large animals are scarce. We sought to determine the effect of DM on macro- and microvascular changes in diabetic pigs and humans. Methods Eight domestic pigs (4 with type I diabetes and 4 controls) underwent coronary angiography with optical coherence tomography (OCT; at baseline and 1 and 2 months), coronary computed tomography angiography, cardiac magnet resonance (CMR) imaging, and histologic examination. Results The diabetic pigs had more irregular capillaries with acellular capillaries and a smaller capillary diameter (11.7 ± 0.33 μm vs. 13.5 ± 0.53 μm; P < 0.001) than those of the control pigs. The OCT showed no significant epicardial stenosis in either group; however diabetic pigs had a greater intima-media thickness. CMR results showed that diabetic pigs had a lower relative upslope at rest (31.3 ± 5.9 vs. 37.9 ± 8.1; P = 0.011) and during stress (18.0 ± 3.0 vs. 21.6 ± 2.8; P = 0.007) than the control pigs, implying decreased myocardial perfusion. Among the 79 patients with ST elevation myocardial infarction, 25 had diabetes and they had lower myocardial perfusion on CMR as well. Conclusion DM causes microvascular remodeling and a decrease in myocardial perfusion in large animals at a very early stage of the disease course. Early and effective interventions are necessary to interrupt the progression of vascular complications in diabetic patients., Graphical Abstract

Tobacco smoking causes cardiovascular diseases, lung disease, and various cancers. Understanding the population-based characteristics associated with smoking and the cause of death is important to improve survival. This study sought to evaluate the differential impact of smoking on cardiac or non-cardiac death according to age. Data from 514,866 healthy adults who underwent national health screening in South Korea were analyzed. The participants were divided into three groups: never-smoker, ex-smoker or current smoker according to the smoking status. The incidence rates and hazard ratios (HRs) of cardiac or non-cardiac deaths according to smoking status and age groups during the 10-year follow-up were calculated to evaluate the differential risk of smoking. Over the follow-up period, 6,192 and 24,443 cardiac and non-cardiac deaths had occurred, respectively. The estimated incidence rate of cardiac and non-cardiac death gradually increased in older age groups and was higher in current smokers and ex-smokers than that in never-smokers among all age groups. After adjustment of covariates, the HRs for cardiac death of current smokers compared to never-smokers were the highest in individuals in their 40’s (1.82; 95% CI, 1.45–2.28); this gradually decreased to 0.96 (95% CI, 0.67–1.38) in individuals >80 years. In contrast, the HRs for non-cardiac death peaked in individuals in their 50’s, (HR 1.69, 95% CI 1.57–1.82) and was sustained in those >80 years (HR 1.40, 95% CI 1.17–1.69). Ex-smokers did not show elevated risk of cardiac death compared to never-smokers in any age group, whereas they showed significantly higher risk of non-cardiac death in their 60’s and 70’s (HR, 1.29; 95% CI, 1.19–1.39; HR 1.22, 95% CI, 1.12–1.32, respectively). Acute myocardial infarction and lung cancer showed patterns similar to those of cardiac and non-cardiac death, respectively. Smoking was associated with higher relative risk of cardiac death in the middle-aged group and non-cardiac death in the older age group. Ex-smokers in the older age group had elevated risk of non-cardiac death. To prevent early cardiac death and late non-cardiac death, smoking cessation should be emphasized as early as possible.

Objective Although chronic kidney disease (CKD) and diabetes are important prognostic factors in patients with peripheral artery disease, there are limited data regarding the outcomes of endovascular treatment (EVT) according to the severity of CKD, especially in the presence of diabetes. This study sought to compare clinical outcomes of lower limb EVT between patients with and patients without CKD according to the presence of diabetes. Methods Patients were enrolled from the Korean multicenter EVT registry and were divided according to the presence of diabetes, then further stratified by CKD (estimated glomerular filtration rate 2 ). The primary outcome was major adverse limb events (MALEs; a composite of reintervention for target limb, reintervention for target vessel, and unplanned major amputation) at 2 years. Results A total of 3045 patients were eligible for analysis: 1277 nondiabetic patients (944 without CKD, 333 with CKD) and 1768 diabetic patients (951 without CKD, 817 with CKD). CKD was associated with a significantly increased risk of MALEs after EVT in diabetic patients (14.4% vs 9.9%; adjusted hazard ratio, 1.60; 95% confidence interval, 1.28-2.01; P P = .203; interaction P = .018). In analysis stratified by the severity of CKD among diabetic patients, end-stage renal disease was significantly associated with an increased risk of MALE. Conclusions CKD was associated with a significantly higher risk of MALEs after EVT in diabetic patients but not in nondiabetic patients. The increased risk of MALEs was mainly driven by patients with end-stage renal disease.

Chronic total occlusion (CTO) is a challenging lesion to cardiologists with limited success rate. The most difficult procedure is to pass a wire through the occluded lesion [1]. However, it is sometimes difficult to deliver devices along the positioned wire. This chapter overviews tips and tricks of successful stent delivery and implantation for the CTO intervention.

Background and Objective: Intra-operative X-ray angiography, the current standard method for visualizing and diagnosing cardiovascular disease, is limited in its ability to provide essential 3D information. These limitations are disadvantages in treating patients. For example, it is a cause of lowering the success rate of interventional procedures. Here, we propose a novel 2D-3D non-rigid registration method to understand vascular geometry during percutaneous coronary intervention. Methods: The proposed method uses the local bijection pair distance as a cost function to minimize the effect of inconsistencies from center-line extraction. Moreover, novel cage-based 3D deformation and multi-threaded particle swarm optimization are utilized to implement real-time registration. We evaluated the proposed method for 154 examinations from 10 anonymous patients by coverage percentage, comparing the average distance of the 2D extracted center-line with that of the registered 3D center-line. Results: The proposed 2D-3D non-rigid registration method achieved an average distance of 1.98 mm with a 0.54 s computation time. Additionally, in aiming to reduce the uncertainty of XA images, we used the proposed method to retrospectively visualize the connections between 2D vascular segments and the distal part of occlusions. Conclusions: Ultimately, the proposed 2D/3D non-rigid registration method can successfully register the 3D center-line of coronary arteries with corresponding 2D XA images, and is computationally sufficient for online usage. Therefore, this method can improve the success rate of such procedures as a percutaneous coronary intervention and provide the information necessary to diagnose cardiovascular diseases better.

The authors performed this analysis to examine whether the enhanced clopidogrel responsiveness in current smokers is maintained after adjusting the influence of hemoglobin on VerifyNow P2Y12 reaction unit (PRU).PRU is consistently reported to be lower in current smokers. However, PRU has a significant inverse relationship with hemoglobin level, and smokers have higher hemoglobin levels. Because the association between PRU and hemoglobin is likely to be an in vitro phenomenon, we hypothesized that the observed difference in PRU between nonsmokers and current smokers is the result of confounding effect of hemoglobin rather than true difference in platelet reactivity.Three cohorts were combined for the analysis (SNUBH [Seoul National University Bundang Hospital], n = 459; CILON-T [influence of CILostazol-based triple antiplatelet therapy ON ischemic complication after drug-eluting stenT implantation], n = 715; HOST-ASSURE [Harmonizing Optimal Strategy for Treatment of coronary artery stenosis - sAfetyeffectiveneSS of drug-elUting stentsantiplatelet REgimen], n = 1,357). The final combined cohort consisted of 1,314 patients who underwent percutaneous coronary intervention and had VerifyNow P2Y12 assay results. General linear model (analysis of covariance) was used to control the effect of hemoglobin on PRU.A significant inverse correlation was observed between PRU and hemoglobin (r = -0.389; p 0.001). Current smokers showed a significantly higher hemoglobin level (13.5 ± 1.6 vs. 14.4 ± 1.5; p 0.001) but lower PRU level (230.1 ± 90.7 vs. 212.2 ± 83.6; p 0.001). After adjusting the influence of hemoglobin on PRU, there was no difference in PRU between nonsmokers and current smokers (224.1 [95% confidence interval: 218.7 to 229.5] vs. 225.3 [95% confidence interval: 217.2 to 233.3]; p = 0.813).The observed difference in PRU between nonsmokers and current smokers is largely attributable to the difference in hemoglobin level. Enhanced clopidogrel responsiveness in cigarette smokers is not confirmed in this study and the concept of the smokers' paradox needs further validation.

Several studies have reported a high rate of RHOA mutations in the Lauren diffuse-type gastric adenocarcinoma (GA) but not in intestinal-type GA. The aim of this study was to determine if RhoA activity is prognostic for overall survival (OS) in patients with resectable GA.Retrospective review was performed on a prospective database of GA patients who underwent potentially curative resection between 2003 and 2012 at a single institution. Tissue microarrays were constructed from surgical specimens and analyzed for phosphorylated RhoA, a marker of inactive RhoA signaling. OS was estimated by the Kaplan-Meier method, and multivariate analysis was performed by Cox proportional hazards regression modeling.One hundred thirty-six patients with diffuse-type GA and 129 patients with intestinal-type GA were examined. Compared to intestinal-type GA, diffuse-type GA tumors were significantly associated with increased tumor size and advanced tumor, node, metastasis (TNM) classification system stage. In patients with diffuse-type GA, high RhoA activity was associated with significantly worse OS when compared to low RhoA activity (5-year OS 52.5 vs. 81.0 %, p = 0.017). This difference in OS was not observed in patients with intestinal-type GA (5-year OS 83.9 vs. 81.6 %, p = 0.766). On multivariate analysis of diffuse-type GA patients, high RhoA activity was an independent negative prognostic factor for OS (hazard ratio 2.38, 95 % confidence interval 1.07-5.28).Increased RhoA activity is predictive of worse OS in patients with diffuse-type GA who undergo potentially curative surgical resection. Along with findings from genomic studies, these results suggest RhoA may be a novel therapeutic target in diffuse-type GA.

Background and Purpose Left ventricular (LV) diastolic dysfunction, developed in relation to myocardial dysfunction and remodeling, is documented in 15%-25% of the population. However, its role in functional recovery and recurrent vascular events after acute ischemic stroke has not been thoroughly investigated. Methods In this retrospective observational study, we identified 2,827 ischemic stroke cases with adequate echocardiographic evaluations to assess LV diastolic dysfunction within 1 month after the index stroke. The peak transmitral filling velocity/mean mitral annular velocity during early diastole (E/e’) was used to estimate LV diastolic dysfunction. We divided patients into 3 groups according to E/e’ as follows

Hematopoiesis is regulated by crosstalk between long-term repopulating hematopoietic stem cells (LT-HSCs) and supporting niche cells in the bone marrow (BM). Here, we examine the role of CD82/KAI1 in niche-mediated LT-HSC maintenance. We found that CD82/KAI1 is expressed predominantly on LT-HSCs and rarely on other hematopoietic stem-progenitor cells (HSPCs). In Cd82(-/-) mice, LT-HSCs were selectively lost as they exited from quiescence and differentiated. Mechanistically, CD82-based TGF-β1/Smad3 signaling leads to induction of CDK inhibitors and cell-cycle inhibition. The CD82 binding partner DARC/CD234 is expressed on macrophages and stabilizes CD82 on LT-HSCs, promoting their quiescence. When DARC(+) BM macrophages were ablated, the level of surface CD82 on LT-HSCs decreased, leading to cell-cycle entry, proliferation, and differentiation. A similar interaction appears to be relevant for human HSPCs. Thus, CD82 is a functional surface marker of LT-HSCs that maintains quiescence through interaction with DARC-expressing macrophages in the BM stem cell niche.

Recent evidence suggests that the gut microbiome plays a role in the development of coronary artery diseases. In this study, we investigated whether microbial signature is detected in the coronary thrombus and how its composition is related with the oral and gut microbiome of the patients with ST

Coronavirus disease 2019 (COVID-19) is a highly contagious disease caused by the novel virus severe acute respiratory syndrome coronavirus-2. The first case developed in December, 2019 in Wuhan, China; several months later, COVID-19 has become pandemic, and there is no end in sight. This disaster is also causing serious health problems in the area of cardiovascular intervention. In response, the Korean Society of Interventional Cardiology formed a COVID-19 task force to develop practice guidelines. This special article introduces clinical practice guidelines to prevent secondary transmission of COVID-19 within facilities; the guidelines were developed to protect patients and healthcare workers from this highly contagious virus. We hope these guidelines help healthcare workers and cardiovascular disease patients around the world cope with the COVID-19 pandemic.

AIMS It is unclear whether a J-curve association exists in cardiovascular risk prediction and how independently systolic and diastolic blood pressure (BP) predict cardiovascular outcomes. This study evaluated the association of systolic and diastolic BP with major cardiovascular events to clarify these issues. METHODS AND RESULTS Antihypertensive medication-naive subjects with available BP measurements and no history of cardiovascular events were extracted from the National Health Insurance Services Health Screening Cohort. The study endpoint was a composite of cardiac death, myocardial infarction, stroke, and heart failure. The study population comprised 290 600 subjects (median follow-up duration 6.7 years). The risk for major cardiovascular events was lowest at systolic and diastolic BPs of 90-99 mmHg and 40-49 mmHg, respectively, above which BPs demonstrated a log-linear risk prediction. Systolic and diastolic BPs were highly correlated. The risk prediction of diastolic BP was inconsistent when stratified by systolic BP. A wider pulse pressure rather than a higher diastolic BP was significantly associated with cardiovascular outcomes among men aged ≥55 years. In addition, the difference between diastolic BPs of

Background We conducted a randomized controlled trial to investigate whether an additional platelet inhibition with tirofiban would reduce the extent of myocardial damage and prevent periprocedural myonecrosis in patients with Non-ST-elevation acute coronary syndrome (NSTE-ACS) with a high residual platelet activity (HPR). Methods Patients with an HPR, defined as P2Y12 reaction unit (PRU) > 230, were randomly assigned to group A (tirofiban treatment, n = 30) or C1 (n = 30) and patients without an HPR to C2 (n = 78). Periprocedural myocardial damage was assessed using the area under the curve (AUC) of serial cardiac enzyme levels from the time of the procedure to post-36 h. Periprocedural myonecrosis incidence was evaluated. Results The troponin I AUC was not different between the groups (197.2 [41.5395.7], 37.9 [8.9313.9], 121.3 [43.7481.8] h∙ng/mL; p = 0.088). The results did not change when the baseline levels were adjusted (365.3 [279.5, 451.1], 293.0 [207.1, 379.0], and 298.0 [244.7, 351.3] h∙ng/mL; p = 0.487). The rate of periprocedural myonecrosis was also not different between the groups (53.0% vs. 50.0% vs. 33.3%, p = 0.092). The CK-MB isoenzyme analysis showed similar results. No difference in complications was noted. Conclusion Additional tirofiban administration was not beneficial to patients with NSTE-ACS even with an HPR. Trial registration Clinical trial no. NCT03114995, registered 11 April, 2017, retrospectively. Electronic supplementary material The online version of this article (10.1186/s12872-018-0938-6) contains supplementary material, which is available to authorized users.

Sarcomas are malignant tumors derived from mesenchymal tissues and may harbor a subset of cells with cancer stem-like cell (CSC) properties. Platelet-derived growth factor receptors α and β (PDGFR-α/β) play an important role in the maintenance of mesenchymal stem cells. Here we examine the role of PDGFR-α/β in sarcoma CSCs. PDGFR-α/β activity and the effects of PDGFR-α/β inhibition were examined in 3 human sarcoma cell lines using in vitro assays and mouse xenograft models. In all three cell lines, PDGFR-α/β activity was significantly higher in cells grown as spheroids (to enrich for CSCs) and in cells sorted for CD133 expression (a marker of sarcoma CSCs). Self-renewal transcription factors Nanog, Oct4, and Slug and epithelial-to-mesenchymal transition (EMT) proteins Snail, Slug, and Zeb1 were also significantly higher in spheroids cells and CD133(+) cells. Spheroid cells and CD133(+) cells demonstrated 2.9- to 4.2-fold greater migration and invasion and resistance to doxorubicin chemotherapy. Inhibition of PDGFR-α/β in CSCs using shRNA or pharmacologic inhibitors reduced expression of certain self-renewal and EMT proteins, reduced spheroid formation by 74–82%, reduced migration and invasion by 73–80%, and reversed chemotherapy resistance. In mouse xenograft models, combining PDGFR-α/β inhibition (using shRNA or imatinib) with doxorubicin had a more-than-additive effect in blocking tumor growth, with enhanced apoptosis, especially in CD133(+) cells. These results indicate that PDGFR-α/β activity is upregulated in sarcoma CSCs and promote CSC phenotypes including migration, invasion, and chemotherapy resistance. Thus, the PDGFR-α/β pathway represents a new potential therapeutic target to reduce metastatic potential and increase chemosensitivity.