Search

Novel antimicrobials are urgently needed to combat methicillin-resistant Staphylococcus aureus (MRSA) infections. This study explores the potential of biosurfactants derived from Bacillus rugosus HH2 as a novel antibacterial agent against MRSA. The biosurfactant, identified as surfactin, demonstrated surface-active properties, reducing surface tension to 37.63 mN/m and lowering contact angles in a concentration-dependent manner. It remained stable across a wide range of pH (4-10), temperatures (30-80 °C), and salinity levels (3-18 %). The biosurfactant inhibited the growth of both methicillin-sensitive S. aureus and MRSA, with minimum inhibitory concentrations ranging from 128 to 256 μg/mL. Additionally, it showed anti-biofilm activity, preventing biofilm formation and dispersing established biofilms. Field-emission scanning electron microscopy revealed that the biosurfactant disrupted bacterial cell membranes, leading to leakage. Furthermore, it reduced the production of virulence factors in S. aureus, including hemolysin and lipase. Transcriptomic analysis indicated downregulation of genes associated with quorum sensing and cell adhesion in MRSA. Molecular docking studies showed strong interactions between surfactin and key MRSA proteins, underscoring its potential to overcome antibiotic resistance. Biocompatibility was confirmed through in vitro cytotoxicity and in vivo phytotoxicity tests. In summary, this study presents surfactin as a promising novel antibacterial agent against MRSA, providing insights into its mechanisms of action., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Various wound dressings are under development to accelerate wound healing, and hydrogels in particular have the potential to create ideal conditions for wound healing. In this study, we investigated a novel hydrogel based on gelatin/oxidized carboxymethyl cellulose loaded with fucoidan derived from Ecklonia cava (ECF) for wound treatment. The mechanical stability and self-healing ability of the hydrogel were optimized, and its cytocompatibility was demonstrated against RAW 264.7 macrophages and human dermal fibroblasts (HDF). Furthermore, sustained drug release from the fabricated hydrogels depending on ECF concentration exhibited radical scavenging ability, induction of collagen production, promotion of cell migration, reduction of nitric oxide levels, and cytoprotective effects against oxidative stress in the ROS microenvironment, attributing these effects to the wound healing potential of bioactive ECF. In an in vivo experiments, GOC/F5 hydrogel was shown to significantly reduce wound area in a full-thickness ICR mouse model, and promoted re-epithelialization and collagen deposition to rapidly repair wounds. These results suggest that GOC/F5 hydrogels could be potentially used as an ideal dressing for wound healing., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Study Objective: This study aimed to analyze the effects of two volatile anesthetic agents, desflurane and sevoflurane, on graft outcomes in patients undergoing deceased donor liver transplantation (DDLT) for cirrhosis, with a specific focus on fatty grafts., Design: A retrospective observational study., Setting: A tertiary hospital (Severance Hospital, Korea)., Patients: This study included 151 patients with liver cirrhosis who underwent DDLT for cirrhosis between January 2006 and December 2022., Interventions: Patients were grouped according to maintenance anesthesia received (desflurane or sevoflurane), the model for end-stage liver disease (MELD) score, and macrovesicular steatosis (MVS) of the liver graft., Measurements: Survival curves were constructed from the date of surgery to graft failure or death. After propensity score matching (PSM), Cox regression analysis was used to compare hazards ratios (HR) for 5-year graft and overall survival. Subgroup analyses were performed for the MELD score and MVS of the liver graft. Incidences of 1-month acute rejection and early allograft dysfunction (EAD) were also compared between the two groups., Main Results: Among 151 eligible patients, 49 patients remained in each group after PSM, with 14 (28.6 %) graft failures and deaths occurring in each group. In matched analysis, sevoflurane showed poorer 5-year graft and overall survival compared to desflurane in recipients of graft with ≥10 % MVS, and this trend was significant in patients with MELD score of ≥35. In Cox regression model, compared to desflurane sevoflurane showed a propensity score-matched HR of 5.8 (95 % CI, 1.13-30.50 for both 5-year graft and overall survival. Additionally, sevoflurane showed an increased risk of 1-month acute rejection; however, no difference was observed for EAD., Conclusions: Sevoflurane as a maintenance agent during DDLT in recipients with high MELD scores and fatty grafts may be associated with poorer outcomes compared to desflurane., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Although the correlation between hyperuricemia and cardiovascular disease (CVD) is well known, there have been limited data regarding the impact of hyperuricemia on long-term clinical outcomes in patients with peripheral arterial disease (PAD) after percutaneous transluminal angioplasty (PTA)., Methods: A total of 718 patients who underwent PTA for PAD were enrolled. The patients were divided into the hyperuricemia group (N = 168) and the normal group (N = 550). Hyperuricemia was defined as a uric acid level ≥ 7.0 mg/dL in men, and ≥ 6.5 mg/dL in women. The primary endpoint was major adverse cerebral and cardiovascular event (MACCE), including death, myocardial infarction (MI), any coronary revascularization, and stroke, up to 5 years. The secondary endpoint was major adverse limb event (MALE), including any repeated PTA, and target extremity surgery (TES). Inverse probability weighting (IPTW) analysis, derived from the logistic regression model, was performed to adjust potential confounders., Results: After IPTW matching analysis, compared to the normal group, the hyperuricemia group was not associated with increased MACCE but was associated with an increased incidence of MI (2.6 % vs. 0.5 %, p = 0.001), and coronary revascularization (6.7 % vs. 3.9 %, p = 0.018). Also, the hyperuricemia group was associated with a higher incidence of MALE (45.3 % vs. 28.9 %, p < 0.001), including target extremity revascularization (TER; 25.1 % vs. 15.9 %, p < 0.001), non-TER (11.5 % vs. 5.6 %, p < 0.001), and TES (22.8 % vs. 16.2 %, p = 0.002)., Conclusions: In the present study, hyperuricemia was associated with worse clinical outcomes in PAD patients following PTA during 5-year clinical follow-up. Further investigations should be made regarding the clinical benefit of controlling hyperuricemia on clinical outcomes., Competing Interests: Declaration of competing interest All authors have no financial conflicts of interest relevant to the manuscript to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Motor imagery (MI)-based brain-computer interfaces are widely employed for improving the rehabilitation of paralyzed people and their quality of life. It has been well documented that brain activity patterns in the primary motor cortex and sensorimotor cortex during MI are similar to those of motor execution/imagery. However, individuals paralyzed owing to various neurological disorders have debilitated activation of the motor control region. Therefore, the differences in brain activation based on the paralysis location should be considered. We analyzed brain activation patterns using the electroencephalogram (EEG) acquired while performing MI on the right upper limb to investigate hemiplegia-related brain activation patterns. Participants with hemiplegia of the right upper limb (n=7) and left upper limb (n=4) performed the MI task within the right upper limb. EEG signals were acquired using 14 channels based on a 10-20 global system, and analyzed for event-related desynchronization (ERD) based on event-related spectral perturbation and functional connectivity, using the weighted phase-lag index of both hemispheres at the location of hemiplegia. Enhanced ERD was found in the ipsilateral region, compared to the contralateral region, after MI of the affected limb. The reduced difference in the centrality of the channels was observed in all subjects, likely reflecting an altered brain network from increased interhemispheric connections. Furthermore, the tendency of distinct network-based features depending on the MI task on the affected limb was diluted between the inter-hemispheres. Analysis of interaction between inter-region using functional connectivity could provide avenues for further investigation of BCI strategy through the brain state of individuals with hemiplegia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Objectives: The risk factors for late-onset Pneumocystis jirovecii pneumonia (PCP) after liver transplantation (LT) have not been well studied. We aimed to analyze the clinical features preceding PCP in LT recipients that would guide individualized prophylaxis., Methods: Among 742 patients who underwent LT and routine PCP prophylaxis from January 2009 through December 2019 at Severance Hospital, 27 patients developed PCP. We conducted a retrospective case-control study matching each patient with four controls and analyzed the risk factors for late-onset PCP., Results: After 6 months, post-transplant PCP cases increased steadily with an overall incidence of 6.36 cases per 1000 patient-year. The PCP-related mortality was 37.0%. In the multivariate analyses, age at LT ≥65 years (odds ratio [OR], 13.305; 95% confidence interval [CI], 2.507-70.618; P = 0.002), cytomegalovirus infection (OR, 5.390; 95% CI, 1.602-18.132; P = 0.006), steroid pulse therapy (OR, 6.564; 95% CI, 1.984-21.719; P = 0.002), hepatocellular carcinoma recurrence (OR, 18.180; 95% CI, 3.420-96.636; P = 0.001), and lymphocytopenia (OR, 3.758; 95% CI, 1.176-12.013; P = 0.026) were independently associated with PCP., Conclusion: Late-onset PCP after routine prophylaxis after LT remains a lethal infection and is associated with age ≥65 years at LT, cytomegalovirus infection, steroid pulse therapy, hepatocellular carcinoma recurrence, and lymphocytopenia. Targeted prophylaxis considering these risk factors could improve the prevention of this potentially lethal complication., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background & Aims: The liver provides a unique niche of lymphocytes enriched with a large proportion of innate-like T cells. However, the heterogeneity and functional characteristics of the hepatic T-cell population remain to be fully elucidated., Methods: We obtained liver sinusoidal mononuclear cells from the liver perfusate of healthy donors and recipients with HBV-associated chronic liver disease (CLD) during liver transplantation. We performed a CITE-seq analysis of liver sinusoidal CD45 + cells in combination with T cell receptor (TCR)-seq and flow cytometry to examine the phenotypes and functions of liver sinusoidal CD8 + T cells., Results: We identified a distinct CD56 hi CD161 - CD8 + T-cell population characterized by natural killer (NK)-related gene expression and a uniquely restricted TCR repertoire. The frequency of these cells among the liver sinusoidal CD8 + T-cell population was significantly increased in patients with HBV-associated CLD. Although CD56 hi CD161 - CD8 + T cells exhibit weak responsiveness to TCR stimulation, CD56 hi CD161 - CD8 + T cells highly expressed various NK receptors, including CD94, killer immunoglobulin-like receptors, and NKG2C, and exerted NKG2C-mediated NK-like effector functions even in the absence of TCR stimulation. In addition, CD56 hi CD161 - CD8 + T cells highly respond to innate cytokines, such as IL-12/18 and IL-15, in the absence of TCR stimulation. We validated the results from liver sinusoidal CD8 + T cells using intrahepatic CD8 + T cells obtained from liver tissues., Conclusions: In summary, the current study found a distinct CD56 hi CD161 - CD8 + T-cell population characterized by NK-like activation via TCR-independent NKG2C ligation. Further studies are required to elucidate the roles of liver sinusoidal CD56 hi CD161 - CD8 + T cells in immune responses to microbial pathogens or liver immunopathology., Lay Summary: The role of different immune cell populations in the liver is becoming an area of increasing interest. Herein, we identified a distinct T-cell population that had features similar to those of natural killer (NK) cells - a type of innate immune cell. This distinct population was expanded in the livers of patients with chronic liver disease and could thus have pathogenic relevance., Competing Interests: Conflict of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: The purpose of the present study was to investigate which peri-transplant dental treatments were deemed necessary, and to determine retrospectively how often these treatments were actually performed, in patients who had received organ transplants., Materials and Methods: Medical records of the Department of Advanced General Dentistry at Yonsei University Dental Hospital were searched to identify liver or kidney transplant recipients who attended from 1st March 2014 to 31st December 2017. A total of 418 patients were identified, and their medical charts were reviewed. Sex, underlying systemic disease, oral hygiene status, dental treatment deemed necessary, dental treatment actually performed and durations of follow-up were tabulated., Results: More than half (53.8%) of the liver transplant recipients had poor oral hygiene, and poor oral hygiene was statistically significantly more prevalent in the liver transplant group than in the kidney transplant group (40.3%). In liver recipients in whom scaling was deemed to be required pre-transplant, the rate of it actually being performed pre-transplant was high (83.2%). By contrast, the rates of tooth extraction and prosthetic treatment actually being performed pre-transplant were low (12.8% and 0%, respectively). In kidney recipients, the rates of scaling, tooth extraction and prosthetic treatment actually performed pre-transplant, when deemed to be required, were 93.5%, 10.0% and 0.0%, respectively., Conclusions: We recommend that patients scheduled to receive an organ transplant be referred to a dental clinic as soon as possible beforehand, to remove any potential sources of oral infection. Educating physicians, as well as their patients, about the importance of early dental screening and pre-transplant dental treatment is essential., (© 2020 FDI World Dental Federation.)

Background and Aims: Sarcopenia is associated with fibrotic burden in patients with chronic hepatitis B. We investigated the dynamic association between fibrosis changes and appendicular skeletal muscle mass during antiviral therapy in patients with chronic hepatitis B., Methods: Between 2015 and 2018, chronic hepatitis B patients who received paired transient elastography to assess fibrotic burden in the liver and bioelectrical impedance analysis to assess appendicular skeletal muscle mass were recruited retrospectively. The sarcopenia index was calculated as total appendicular skeletal muscle mass/body mass index. Significant liver fibrosis was defined as a liver stiffness value≥8 kPa., Results: In total, 223 (53.7%) received antiviral therapy, whereas 192 (46.3%) did not. Appendicular skeletal muscle mass decreased significantly in the antiviral therapy group (mean 21.16→21.00 kg, P = 0.01), but not in the non-antiviral therapy group (mean 20.77→20.64 kg, P = 0.134). In a subgroup with significant liver fibrosis, similar findings were observed (mean 20.73→20.54 kg in antiviral therapy group, P = 0.037; mean 21.39→21.07 kg in the non-antiviral therapy group, P = 0.097). Older age, male gender, higher body mass index, and higher aspartate aminotransferase were significantly associated with the increased risk of appendicular skeletal muscle mass reduction (≥5% from the baseline)., Conclusions: Appendicular skeletal muscle mass significantly decreased during antiviral therapy in patients with chronic hepatitis B patients., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background & Aims: Mucosal-associated invariant T (MAIT) cells, the most abundant innate-like T cells in the human liver, can be activated by cytokines during viral infection without TCR stimulation. Here, we examined the mechanisms underlying TCR/MR1-independent innate-like cytotoxicity of cytokine-activated liver MAIT cells. We also examined the phenotype and function of MAIT cells from patients with acute viral hepatitis., Methods: We obtained liver sinusoidal mononuclear cells from donor liver perfusate during liver transplantation and examined the effect of various cytokines on liver MAIT cells using flow cytometry and in vitro cytotoxicity assays. We also obtained peripheral blood and liver-infiltrating T cells from patients with acute hepatitis A (AHA) and examined the phenotype and function of MAIT cells using flow cytometry., Results: IL-15-stimulated MAIT cells exerted granzyme B-dependent innate-like cytotoxicity in the absence of TCR/MR1 interaction. PI3K-mTOR signaling, NKG2D ligation, and CD2-mediated conjugate formation were critically required for this IL-15-induced innate-like cytotoxicity. MAIT cells from patients with AHA exhibited activated and cytotoxic phenotypes with higher NKG2D expression. The innate-like cytotoxicity of MAIT cells was significantly increased in patients with AHA and correlated with serum alanine aminotransferase levels., Conclusions: Taken together, the results demonstrate that liver MAIT cells activated by IL-15 exert NKG2D-dependent innate-like cytotoxicity in the absence of TCR/MR1 engagement. Furthermore, the innate-like cytotoxicity of MAIT cells is associated with liver injury in patients with AHA, suggesting that MAIT cells contribute to immune-mediated liver injury., Lay Summary: Immune-mediated liver injury commonly occurs during viral infections of the liver. Mucosal-associated invariant T (MAIT) cells are the most abundant innate-like T cells in the human liver. Herein, we have identified a mechanism by which MAIT cells circumvent conventional T cell receptor interactions to exert cytotoxicity. We show that this innate-like cytotoxicity is increased during acute hepatitis A virus infection and correlates with the degree of hepatocyte injury., Competing Interests: Conflict of interest The authors have no conflicting financial interests. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Regulatory T (Treg) cells are important in preventing acute rejection (AR) in solid organ transplantation, but the clinical relevance of the different kinetics early after liver transplantation (LT) in acute rejectors and non-rejectors is unclear. We analyzed peripheral blood samples of 128 LT recipients receiving basiliximab induction plus tacrolimus immunosuppression. Samples were obtained at pretransplant, D7, and D30 after LT. Frequency and phenotype of Tregs were analyzed by flow cytometry. The predictive value of Treg frequency at D7 was assessed for suspected acute rejection (SAR) and was validated for biopsy-proven AR (BPAR). We found that the frequencies of total and activated Tregs at D7 were significantly lower in recipients with SAR and BPAR. Treg was more reduced in BPARs by in vitro tacrolimus treatment in the presence of basiliximab. Moreover, an early reduction of Treg frequency in rejectors was associated with a greater increase in Treg apoptosis and further attenuated IL-2 signaling. D7 Treg frequency was an independent risk factor for SAR, which was also validated for BPAR. In conclusion, first-week peripheral blood Treg frequency correlates with AR after LT under tacrolimus-based immunosuppression, which needs to be proven in larger, geographically and clinically diverse populations., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background & Aims: Human liver CD69 + CD8 + T cells are ~95% CD103 - and ~5% CD103 + . Although CD69 + CD103 + CD8 + T cells show tissue residency and robustly respond to antigens, CD69 + CD103 - CD8 + T cells are not yet well understood., Methods: Liver perfusate and paired peripheral blood were collected from healthy living donors and recipients with cirrhosis during liver transplantation. Liver tissues were obtained from patients with acute hepatitis A. Phenotypic and functional analyses were performed by flow cytometry. Gene expression profiles were determined by microarray and quantitative reverse transcription PCR. PT-2385 was used to inhibit hypoxia-inducible factor (HIF)-2α., Results: Human liver CD69 + CD103 - CD8 + T cells exhibited HIF-2α upregulation with a phenotype of tissue residency and terminal differentiation. CD103 - cells comprised non-hepatotropic virus-specific T cells as well as hepatotropic virus-specific T cells, but CD103 + cells exhibited only hepatotropic virus specificity. Although CD103 - cells were weaker effectors on a per cell basis than CD103 + cells, following T cell receptor or interleukin-15 stimulation, they remained the major CD69 + CD8 + effector population in the liver, surviving with less cell death. An HIF-2α inhibitor suppressed the effector functions and survival of CD69 + CD103 - CD8 + T cells. In addition, HIF-2α expression in liver CD69 + CD103 - CD8 + T cells was significantly increased in patients with acute hepatitis A or cirrhosis., Conclusions: Liver CD69 + CD103 - CD8 + T cells are tissue resident and terminally differentiated, and their effector functions depend on HIF-2α. Furthermore, activation of liver CD69 + CD103 - CD8 + T cells with HIF-2α upregulation is observed during liver pathology., Lay Summary: The immunologic characteristics and the role of CD69 + CD103 - CD8 + T cells, which are a major population of human liver CD8 + T cells, remain unknown. Our study shows that these T cells have a terminally differentiated tissue-resident phenotype, and their effector functions depend on a transcription factor, HIF-2α. Furthermore, these T cells were activated and expressed higher levels of HIF-2α in liver pathologies, suggesting that they play an important role in immune responses in liver tissues and the pathogenesis of human liver disease., Competing Interests: Conflict of interest The authors have no conflicting financial interests. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

In a multicenter, open-label, study, 284 living-donor liver transplant patients were randomized at 30 ± 5 days posttransplant to start everolimus+reduced tacrolimus (EVR+rTAC) or continue standard tacrolimus (TAC Control). EVR+rTAC was non-inferior to TAC Control for the primary efficacy endpoint of treated BPAR, graft loss or death at 12 months posttransplant: difference -0.7% (90% CI -5.2%, 3.7%); P < .001 for non-inferiority. Treated BPAR occurred in 2.2% and 3.6% of patients, respectively. The key secondary endpoint, change in estimated glomerular filtration rate (eGFR) from randomization to month 12, achieved non-inferiority (P < .001 for non-inferiority), but not superiority and was similar between groups overall (mean -8.0 vs. -12.1 mL/min/1.73 m 2 , P = .108), and in patients continuing randomized treatment (-8.0 vs. -13.3 mL/min/1.73 m 2 , P = .046). In the EVR+rTAC and TAC control groups, study drug was discontinued in 15.5% and 17.6% of patients, adverse events with suspected relation to study drug occurred in 57.0% and 40.4%, and proteinuria ≥1 g/24 h in 9.3% and 0%, respectively. Everolimus did not negatively affect liver regeneration. At 12 months, hepatocellular recurrence was only seen in the standard TAC-treated patients (5/62; 8.1%). In conclusion, early introduction of EVR+rTAC was non-inferior to standard tacrolimus in terms of efficacy and renal function at 12 months, with hepatocellular carcinoma recurrence only in TAC Control patients. ClinicalTrials.gov Identifier: NCT01888432., (© 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background and Aims: Myocardial bridge (MB) and coronary artery spasm (CAS) can induce a sustained chest pain, acute coronary syndrome (ACS) and even sudden cardiac death. The aim of this study is to evaluate the relationship between MB and CAS and its impact on long-term clinical outcomes., Methods: A total of 812 patients with MB without significant coronary artery disease (CAD), who underwent acetylcholine (ACH) provocation test, were enrolled. Significant CAS was defined as ≥70% temporary narrowing by ACH test, and MB was defined as the characteristic phasic systolic compression of the coronary artery with a decrease of more than 30% in diameter on the angiogram after intracoronary nitroglycerin infusion. To adjust baseline confounders, logistic regression analysis was performed. The primary endpoint was incidence of CAS, and secondary endpoints were major adverse cardiac events (MACE) and recurrent angina requiring repeat coronary angiography (CAG) at 5 years., Results: MB is closely implicated in a high incidence of CAS, spontaneous spasm, ischemic ECG change and chest pain during ACH provocation test. In addition, MB of various severity and reference vessel size was substantially implicated in CAS incidence, and severe MB was a strong risk factor of CAS. MB patients with CAS were shown to have a higher rate of recurrent angina compared with MB patients without CAS, up to a 5-year follow-up. However, there were no differences regarding the incidence of MACE., Conclusions: Severe MB was associated with high incidence of CAS, and MB patients with CAS were likely to have a higher incidence of recurrent angina. Intensive medical therapy and close clinical follow-up are needed for better clinical outcomes in MB patients with CAS., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Although there have been several reports that prasugrel can improve clinical outcomes, the efficacy and safety of prasugrel is unknown in Korean patients with acute myocardial infarction (AMI) undergoing successful revascularization., Methods: A total of 4421 patients [637 patients were prescribed prasugrel (60/10 or 5mg, loading/maintenance dose) and 3784 patients clopidogrel (600 or 300/75mg)] with AMI undergoing successful revascularization were enrolled from the core clinical cohort of Korea Acute Myocardial Infarction Registry-National Institute of Health., Results: After propensity score matching (637 pairs), there were no significant differences in baseline clinical and procedural characteristics and in-hospital medications between the two groups. The primary efficacy endpoint, defined as the composite of cardiac death, MI, stroke, or target vessel revascularization at 6 months showed no significant difference between prasugrel and clopidogrel (2.4% vs. 2.9%, p=0.593). Also, no difference was observed in the composite of cardiac death, MI, or stroke during hospitalization between two groups (0.8% vs. 0.9%, p=0.762). However, the incidence of in-hospital Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding was significantly higher in prasugrel compared with clopidogrel (5.3% vs. 2.7%, p=0.015). In multivariate linear regression analysis, trans-femoral intervention, use of glycoprotein IIb/IIIa inhibitors, use of calcium channel blocker, and use of prasugrel were independent predictors of in-hospital TIMI major or minor bleeding [odds ratio (OR)=6.918; 95% confidence interval (CI)=2.453-19.510, OR=2.577; 95% CI=1.406-4.724, OR=4.016; 95% CI=1.382-11.668, OR=2.022; 95% CI=1.101-3.714]., Conclusions: Our study shows that the recommended dose of prasugrel had significantly higher in-hospital bleeding complications without reducing ischemic events compared with clopidogrel. However, further large-scale, long-term, randomized clinical trials are required to accurately assess the efficacy and safety of prasgurel and to find out the optimal dose for Korean AMI patients., (Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: Generally, immoderate alcohol consumption is associated with variant angina and accepted as one of the risk factors for coronary artery spasm (CAS), but evidence is lacking in this regard. The aim of this study is to evaluate the impact of alcohol consumption and drinking pattern on CAS by acetylcholine (ACH) provocation test and long-term clinical outcomes., Methods: A total of 5491 patients with typical or atypical chest pain, without significant coronary artery disease, who underwent intracoronary ACH provocation test, were enrolled prospectively, and retrospectively analyzed in this study. They were divided into two groups according to their alcohol drinking status; the current alcohol (CA) drinking group (n = 1792), and non-CA group (n = 3699). To adjust for potential confounders, a propensity score matching (PSM) analysis was performed. The primary endpoint was incidence of CAS, and secondary endpoints were major adverse cardiac events (MACE) and recurrent angina requiring repeat coronary angiography (CAG) at 5 years., Results: After PSM analysis, alcohol consumption was a strong risk factor for CAS. Furthermore, excessive alcohol consumption was correlated with a higher risk for CAS. As compared with the non-CA group, the CA group showed worse angiographic and clinical findings, including higher incidence of CAS (58% vs. 62%, p = 0.016), spontaneous spasm (17% vs. 22%, p = 0.004), multi-vessel spasm (31% vs. 37%, p = 0.009), proximal epicardial spasm (39% vs. 46%, p = 0.002), ischemic electrocardiography changes such as T-inversion (0.4% vs. 1.2%, p < 0.001) and chest pain (42% vs. 46%, p = 0.047) during ACH provocation test. However, the status and pattern of alcohol drinking had no influence on long-term clinical outcomes such as MACE or recurrent angina., Conclusions: Alcohol consumption is a strong risk factor for CAS, and excessive alcohol consumption was correlated with a higher risk for CAS. Further well-designed studies are needed to confirm the results., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Diabetes Mellitus (DM) is an important factor of adverse cardiovascular events in acute ST-segment elevation myocardial infarction (STEMI) patients. Renin-angiotensin-aldosterone system (RAAS) inhibitors is associated with improved clinical outcomes, however, there are limited data comparing the effectiveness of two different RAAS inhibitors in STEMI patients with DM undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES)., Methods: A total of 3811 eligible STEMI patients with DM were enrolled in Korea Acute Myocardial Infarction Registry (KAMIR). They were stratified into two groups: Angiotensin converting enzyme inhibitors (ACEI) group (n=2691) and angiotensin receptor blockers (ARB) group (n=1120). To adjust baseline confounding factors, we performed propensity score matching (PSM) analysis and evaluated individual and composite major clinical outcomes between the two groups up to 2years., Results: After PSM, a total of 1049 well-matched pairs were generated. Baseline clinical, angiographic and procedural characteristics were well-balanced between the two groups. The incidence of death, recurrent myocardial infarction (MI), revascularization and major adverse cardiac events (MACE) were not significantly different between the two groups up to 2years, CONCLUSION: In the present study, ACEI and ARB showed comparable effectiveness and safety on individual and composite clinical outcomes in STEMI patients with DM who underwent successful PCI with DES at least up to 2years., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Coronary artery spasm (CAS) and significant coronary stenosis are known to be major causes of myocardial ischemia. However, their association and the impact of insignificant coronary stenosis (ICS) on long-term clinical outcomes of CAS patients are largely unknown., Methods: A total of 2797 patients without significant coronary artery disease (CAD) who underwent the acetylcholine (ACH) provocation test between November 2004 and October 2010 were enrolled. Significant CAS was defined as having ≥70% of temporary narrowing by ACH test and ICS as having <70% of fixed stenosis on angiography. Patients were divided into two groups: ICS group (n=764) and non-ICS group (n=845). To adjust potential confounders, a propensity score matching (PSM) analysis was performed using the logistic regression model. Primary endpoint was the composite of total death, myocardial infraction (MI), de novo percutaneous coronary intervention (PCI), and cerebrovascular accidents (CVA). Secondary endpoint was the incidence of recurrent angina requiring repeat coronary angiography (CAG) at 3years., Results: After PSM analysis, two well-balanced groups (548 pairs, total=1096) were generated. The baseline clinical characteristics were similar between the two groups. During the ACH test, compared with the non-ICS group, the ICS group had smaller spastic narrowing diameter (0.69±0.35 vs. 0.73±0.37, P=0.039) and incidence of ST-segment depression (4.0% vs. 0.9%, P=0.001). The incidence of primary and secondary endpoints was similar between the two groups up to 3years., Conclusions: Although, the ICS group was expected to have more adverse long-term clinical outcomes, it was not associated with the increased incidence of major adverse clinical outcomes compared with the non-ICS group up to 3years. Longer term follow-up studies are needed., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Acute hyperglycemia on admission is common in acute myocardial infarction (AMI) patients regardless of diabetic status, and is known as one of prognostic factors. However, the effect of hyperglycemia on non-diabetic patients is still on debate., Methods: A total of 12,625 AMI patients (64.0±12.6years, 26.1% female) who were enrolled in Korea Acute Myocardial Infarction Registry-National Institute of Health between November 2011 and December 2015, were classified into 4367 diabetes (65.4±11.6years, 30.4% female) and 8228 non-diabetes (63.3±13years, 23.9% female). Patients were analyzed for in-hospital clinical outcome according to admission hyperglycemic status., Results: In diabetic patients, independent predictors of in-hospital mortality were old age, high HbA 1 C, pre-Thrombolysis In Myocardial Infarction (TIMI) flow 0, left ventricle ejection fraction<40%, cardiogenic shock and ventricular tachycardia. In non-diabetic patients, independent predictors of in-hospital mortality were old age, high admission glucose (≥200mg/dL), pre TIMI flow 0, failed percutaneous coronary intervention, low left ventricle ejection fraction<40%, cardiogenic shock, stent thrombosis and decreased Hb≥5g/dL. In hospital mortality was significantly higher in diabetic patients compared to non-diabetic patients (5.0% vs. 3.4%, p<0.001). However, non-diabetic patients with hyperglycemia have significantly higher mortality compared to diabetic patients (17.4% vs. 7.2%, p<0.001). Comorbidity including cardiogenic shock (p<0.001), cerebral hemorrhage (p=0.012), decreased Hb≥5g/dL (p=0.013), atrioventricular block (p<0.001) and ventricular tachycardia (p=0.007) was higher in non-diabetic with hyperglycemia than in diabetic patients., Conclusions: These findings underscore clinical significance of admission hyperglycemia on in-hospital mortality in non-diabetic AMI patients., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Vitamin D deficiency, defined as a serum 25-hydroxyvitamin D [25(OH)D] concentration <20 ng/mL, is correlated with a more atherogenic lipid profile. However, oral vitamin D supplementation does not lower LDL-cholesterol concentrations or raise HDL-cholesterol concentrations. This uncoupling between association and causation may result from a failure of oral vitamin D to mimic the effect of dermally synthesized vitamin D in response to ultraviolet type B (UVB) light. Objective: We tested the hypothesis that, in vitamin D-deficient adults, the replenishment of vitamin D with UVB exposure would lower LDL-cholesterol concentrations compared with the effect of oral vitamin D 3 supplementation. Design: We performed a randomized clinical trial in vitamin D-deficient adults and compared vitamin D replenishment between subjects who received oral vitamin D 3 ( n = 60) and those who received narrow-band UVB exposure ( n = 58) ≤6 mo. Results: There was no difference in the change from baseline LDL-cholesterol concentrations between oral vitamin D 3 and UVB groups (difference in median of oral vitamin D 3 minus that of UVB: 1.5 mg/dL; 95% CI: -5.0, 7.0 mg/dL). There were also no differences within groups or between groups for changes in total or HDL cholesterol or triglycerides. Transcriptional profiling of skin and blood, however, revealed significant upregulation of immune pathway signaling with oral vitamin D 3 but significant downregulation with UVB. Conclusions: Correcting vitamin D deficiency with either oral vitamin D 3 or UVB does not improve the lipid profile. Beyond cholesterol, these 2 modalities of raising 25(OH)D have disparate effects on gene transcription. This trial was registered at clinicaltrials.gov as NCT01688102., (© 2017 American Society for Nutrition.)

Background and Aims: The impact of vasomotion types on long-term clinical outcomes in patients with coronary artery spasm (CAS) induced by the acetylcholine provocation test (ACH-test) remains unclear., Methods: We evaluated 4644 consecutive patients with typical resting chest pain (CP), but no angiographically significant coronary artery lesion (<50% stenosis), who underwent an ACH-test. According to their vasomotor response, patients were categorized into four types: normal vasomotion (no CP, no ischemic electrocardiographic changes, and no vasoconstriction), microvascular spasm (CP with <75% vasoconstriction but with CP relief after nitroglycerin infusion), epicardial spasm (CP with ≥75% vasoconstriction), and ACH-test inconclusive (vasoconstriction and/or electrocardiographic changes, but no CP). We investigated CP recurrence requiring follow-up angiography and major adverse cardiovascular events (MACEs) during 5 years., Results: CP recurred in 7.9% of patients and was more frequent in abnormal vasomotion types (normal vasomotion, microvascular spasm, epicardial spasm, and inconclusive type: 5.4%, 9.8%, 10.9%, and 8.2%, respectively, log-rank p = 0.009). In multivariate analysis adjusted for medication use after the ACH-test, vasomotion subtype was not an independent predictor, whereas male sex, fixed lesion on baseline angiography, and medications including calcium channel blockers (CCBs), nitrates, and statins were independent positive predictors for recurrent CP. Alcohol consumption at the initial interview was a negative predictor. MACEs were observed in 1.6%, and the incidence was similar among subtypes (p = 0.421)., Conclusions: Recurrent CP and long-term outcomes are independent of vasomotion subtypes, but long-term use of CCBs, nitrates, and statins is a significant predictor for recurrent CP., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Although ticagrelor has been well-known to improve clinical outcomes in patients with acute myocardial infarction (AMI) without increased bleeding risk, its clinical impacts have not been well established in East Asian patients., Methods: Between November 2011 and June 2015, a total of 8010 patients (1377 patients were prescribed ticagrelor and 6633 patients clopidogrel) undergoing successful revascularization were analyzed from Korea Acute Myocardial Infarction Registry-National Institute of Health. The patients who discontinued or occurred in-hospital switching between two antiplatelet agents were excluded., Results: After propensity score matching (1377 pairs), no difference in the composite of cardiac death, MI, stroke, or target vessel revascularization at 6months was observed between two groups (4.2% vs. 4.9%, p=0.499). However, the incidences of in-hospital Thrombolysis In Myocardial Infarction (TIMI) major and minor bleeding were higher in ticagrelor than clopidogrel (2.6% vs. 1.2%, p=0.008; 3.8% vs. 2.5%, p=0.051). The in-hospital mortality was higher in patients with than those without TIMI major bleeding (11.3% vs. 0.9%, p<0.001). In a subgroup analysis, a higher risk for in-hospital TIMI major bleeding with ticagrelor was observed in patients≥75years or with body weight<60kg (odd ratio [OR]=3.209; 95% confidence interval [CI]=1.356-7.592) and in those received trans-femoral intervention (OR=1.996; 95% CI=1.061-3.754)., Conclusions: Our study shows that ticagrelor did not reduce ischemic events yet, however, was associated with increased risk of bleeding complications compared with clopidogrel. Further large-scale, long-term, randomized trials should be required to assess the outcomes of ticagrelor for East Asian patients with AMI., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

This study was conducted to develop a multiplex reverse transcription (RT) PCR for the detection of Anisakis allergens and to investigate the relationship between allergen profiles and anisakid larvae isolated from Scomber japonicus, Trichiurus lepturus, and Conger myriaster in Korea. The species of Anisakis was determined using Anisakis pegreffii-specific PCR and restriction fragment length polymorphism analysis. The prevalence and profiles of five Ani s allergens were examined by multiplex RTPCR. A. pegreffii and Anisakis typica accounted for 97.1 and 2.9%, respectively, of the 140 larvae examined. In A. pegreffii, allergen prevalence was 41.2% for Ani s 1, 72.1% for Ani s 2, 69.9% for Ani s 3, 86.7% for Ani s 4, and 93.4% for Ani s 5. Most A. pegreffii larvae had multiple allergen profiles, and 80.7% of A. pegreffii carried both Ani s 4 and Ani s 5, which are heat-resistant allergens. Fifty-two to 65% of A. pegreffii isolated from S. japonicus and C. myriaster carried all five Ani s allergens.

Objective: Shunt failure is common in hydrocephalic patients. The cerebrospinal fluid (CSF) infusion test enables the assessment of CSF absorption capacity, which is represented by the resistance to CSF outflow (ROUT) However, shunt failure may not only affect the CSF absorption capacity but also the intracranial compliance or compensatory properties. Spectral analysis of the ICP signal obtained during the infusion test may enable the comprehensive assessment of the overall deterioration caused by shunt failure., Material and Methods: A total of 121 hydrocephalic shunted patients underwent the infusion test with continuous intracranial pressure (ICP) and arterial blood pressure (ABP) recording. The maximum amplitudes of three major frequency bandwidths (0.2-2.6, 2.6-4.0 and 4.0-15 Hz, respectively) were calculated from the ICP. Statistical analyses were conducted to identify factors significantly associated with shunt failure, to construct an index (i.e., the shunt response parameter, SRP) for detecting shunt failure, and to define thresholds for ROUT and SRP., Results: The ROUT threshold for detecting shunt failure was 7.59 mmHg/ml/min, and this threshold showed an accuracy of 82.64%. All spectral parameters were found to be significantly associated with shunt patency (p<0.05). The SRP exhibited significantly better accuracy than ROUT in detecting shunt failure (91.74%)., Conclusion: The hydrodynamic assessment of shunted patients enhanced by spectral analysis during the infusion test detected shunt failure with high accuracy. Although further validation is needed, the SRP exhibited promising results., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Psoriasis is present in all racial groups, but in varying frequencies and severity. Considering that small plaque psoriasis is specific to the Asian population and severe psoriasis is more predominant in the Western population, we defined Asian small and intermediate plaque psoriasis as psoriasis subtypes and compared their molecular signatures with the classic subtype of Western large plaque psoriasis. Two different characteristics of psoriatic spreading-vertical growth and radial expansion-were contrasted between subtypes, and genomic data were correlated to histologic and clinical measurements. Compared with Western large plaque psoriasis, Asian small plaque psoriasis revealed limited psoriasis spreading, but IL-17A and IL-17-regulated proinflammatory cytokines were highly expressed. Paradoxically, IL-17A and IL-17-regulated proinflammatory cytokines were lower in Western large plaque psoriasis, whereas T cells and dendritic cells in total psoriatic skin area were exponentially increased. Negative immune regulators, such as CD69 and FAS, were decreased in both Western large plaque psoriasis and psoriasis with accompanying arthritis or obesity, and their expression was correlated with psoriasis severity index. Based on the disease subtype comparisons, we propose that dysregulation of T-cell expansion enabled by downregulation of immune negative regulators is the main mechanism for development of large plaque psoriasis subtypes., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aims: To evaluate the performance of the American College of Cardiology/American Heart Association (ACC/AHA) 2013 Pooled Cohort Equations in the Korean Heart Study (KHS) population and to develop a Korean Risk Prediction Model (KRPM) for atherosclerotic cardiovascular disease (ASCVD) events., Methods: The KHS cohort included 200,010 Korean adults aged 40-79 years who were free from ASCVD at baseline. Discrimination, calibration, and recalibration of the ACC/AHA Equations in predicting 10-year ASCVD risk in the KHS cohort were evaluated. The KRPM was derived using Cox model coefficients, mean risk factor values, and mean incidences from the KHS cohort., Results: In the discriminatory analysis, the ACC/AHA Equations' White and African-American (AA) models moderately distinguished cases from non-cases, and were similar to the KRPM: For men, the area under the receiver operating characteristic curve (AUROCs) were 0.727 (White model), 0.725 (AA model), and 0.741 (KRPM); for women, the corresponding AUROCs were 0.738, 0.739, and 0.745. Absolute 10-year ASCVD risk for men in the KHS cohort was overestimated by 56.5% (White model) and 74.1% (AA model), while the risk for women was underestimated by 27.9% (White model) and overestimated by 29.1% (AA model). Recalibration of the ACC/AHA Equations did not affect discriminatory ability but improved calibration substantially, especially in men in the White model. Of the three ASCVD risk prediction models, the KRPM showed best calibration., Conclusions: The ACC/AHA Equations should not be directly applied for ASCVD risk prediction in a Korean population. The KRPM showed best predictive ability for ASCVD risk., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Contrast-enhanced ultrasound is highly accurate in depicting the vascularity of liver nodules. The aim of this study was to evaluate the usefulness of contrast-enhanced ultrasound for the differentiation of hepatocellular carcinomas from dysplastic nodules in cirrhotic patients with small liver nodules showing atypical or not coincidental typical vascular pattern on two dynamic imaging techniques (computed tomography and magnetic resonance imaging)., Methods: A total of 46 patients with cirrhosis and a liver nodule smaller than 3cm showing an atypical or non-coincident typical vascular pattern on two dynamic imaging techniques, who underwent liver contrast-enhanced ultrasound and ultrasound-guided liver biopsy, were retrospectively reviewed. Contrast-enhanced ultrasound findings were compared with histopathological and clinical data, and with the two dynamic imaging findings., Results: Significantly different contrast-enhanced ultrasound enhancement patterns were observed among dysplastic nodules, Edmondson grade I and grade II-III hepatocellular carcinomas. Ten out of 11 (90.9%) non-hypervascular hepatocellular carcinomas on two dynamic imaging techniques showed a hypervascular pattern on contrast-enhanced ultrasound, and these made it possible to distinguish hepatocellular carcinomas from dysplastic nodules., Conclusion: Contrast-enhanced ultrasound is useful for the differentiation of hepatocellular carcinomas from dysplastic nodules in cirrhotic patients with small liver nodules., (Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Finite element analysis (FEA) is increasingly used to investigate the brain under various pathological changes. Although FEA has been used to study hydrocephalus for decades, previous studies have primarily focused on ventriculomegaly. The present study aimed to investigate the pathologic changes regarding sulcal deformation in normal pressure hydrocephalus (NPH). Two finite element (FE) models-an anatomical brain geometric (ABG) model and the conventional simplified brain geometric (SBG) model-of NPH were constructed. The models were constructed with identical boundary conditions but with different geometries. The ABG model contained details of the sulci geometry, whereas these details were omitted from the SBG model. The resulting pathologic changes were assessed via four biomechanical parameters: pore pressure, von Mises stress, pressure, and void ratio. NPH was induced by increasing the transmantle pressure gradient (TPG) from 0 to a maximum of 2.0 mmHg. Both models successfully simulated the major features of NPH (i.e., ventriculomegaly and periventricular lucency). The changes in the biomechanical parameters with increasing TPG were similar between the models. However, the SBG model underestimated the degree of stress across the cerebral mantle by 150% compared with the ABG model. The SBG model also overestimates the degree of ventriculomegaly (increases of 194.5% and 154.1% at TPG = 2.0 mmHg for the SBG and ABG models, respectively). Including the sulci geometry in a FEA for NPH clearly affects the overall results. The conventional SBG model is inferior to the ABG model, which accurately simulated sulcal deformation and the consequent effects on cortical or subcortical structures. The inclusion of sulci in future FEA for the brain is strongly advised, especially for models used to investigate space-occupying lesions., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: High dose atorvastatin is known to be associated with new onset diabetes mellitus (NODM) in patients with high risk for developing diabetes mellitus (DM). However, low dose atorvastatin is more commonly used as compared with high dose atorvastatin. The aim of this study is to investigate the impact of low dose atorvastatin (LDA, 10mg or 20mg) on the development of NODM up to three years in Asian patients., Methods: From January 2004 to September 2009, we investigated a total of 3566 patients who did not have DM. To adjust for potential confounders, a propensity score matching (PSM) analysis was performed using the logistic regression model. After PSM (C-statistics: 0.851), a total of 818 patients (LDA group, n=409 patients and control group, n=409 patients) were enrolled for analysis., Results: Before PSM, the cumulative incidence of NODM (5.8% vs. 2.1%, p<0.001), myocardial infarction (0.5% vs. 0.1%, p-value=0.007), and major adverse cardio-cerebral event (MACCE, 1.8% vs. 0.7%, p-value=0.012) at three-years were higher in the LAD group. However, after PSM, there was a trend toward higher incidence of NODM (5.9% vs. 3.2%, p=0.064) in the LDA group, but the incidence of MACCE (1.2% vs. 1.5%, p-value=1.000) was similar between the two groups. In multivariable analysis, the LDA administration was tended to be an independent predictor of NODM (OR: 1.99, 95% CI: 1.00-3.98, p-value 0.050)., Conclusions: In this study, the use of LDA tended to be a risk factor for NODM in Asian patients and reduced clinical events similar to the control group. However, large-scale randomized controlled trials will be needed to get the final conclusion., (Copyright © 2015. Published by Elsevier Ireland Ltd.)

Background: Coronary artery spasm (CAS) is known to be a risk factor of acute coronary syndrome and angina pectoris. However, there is no currently available data with larger study population regarding long-term clinical outcomes of CAS in real world clinical practice., Objectives: We evaluated the prevalence of CAS and the impact of CAS on 5-year clinical outcomes in a series of Asian CAS patients documented by intracoronary acetylcholine (Ach) provocation test., Methods: A total of 1413 consecutive patients without significant coronary artery disease (CAD) who underwent Ach provocation test between Nov. 2004 and Oct. 2008 were enrolled. Significant CAS was defined as >70% of narrowing by incremental intracoronary injection of 20, 50 and 100 μg. Patients were divided into two groups based on the presence of significant CAS (the non-CAS group: n=640, the CAS group; n=773). To adjust potential confounders, a propensity score matched (PSM) analysis was performed using the logistic regression model., Results: A total of 54.7% (773/1413) patients were diagnosed as CAS documented by Ach provocation test. After PSM analysis, 2 propensity-matched groups (451 pairs, n=902, C-statistic=0.677) were generated. Despite of similar incidence of individual hard endpoints including mortality, myocardial infarction and revascularization, the CAS group showed the higher trend of recurrent angina requiring follow up angiography than the non-CAS group up to 5 years (HR; 1.56, 95% C.I.; 0.99-2.46, p=0.054)., Conclusions: The prevalence of CAS was 54.7%. Although the cumulative incidence of recurrent angina requiring follow up coronary angiography seems to be increased up to 5 years in CAS patients, CAS patients was not associated with major individual and composite clinical outcomes such as mortality, MI, PCI, CVA with optimal medical therapy as compared with patients without CAS., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Although posterior wall of left atrium (LA) is known to be arrhythmogenic focus, little is known about the effect of posterior wall isolation (PWI) in patients who undergo radiofrequency catheter ablation (RFCA) for persistent atrial fibrillation (PeAF)., Methods: We randomly assigned 120 consecutive PeAF patients to additional PWI [PWI (+), n=60] or control [PWI (-), n=60] groups. In all patients, linear ablation was performed after circumferential pulmonary vein isolation (PVI). Linear lesions included roof, anterior perimitral, and cavotricuspid isthmus lines with conduction block. In PWI (+) group, posterior inferior linear lesion was also conducted. Creatine kinase-MB (CK-MB) and troponin-T levels were measured 1day after RFCA. LA emptying fraction (LAEF) was assessed before and 12 months after RFCA., Results: A total of 120 subjects were followed for 12 months after RFCA. There were no significant differences between two groups in baseline demographics and LA volume (LAV). The levels of CK-MB and troponin-T and procedure time were not significantly different between the groups. AF termination during RFCA was more frequently observed in PWI (+) than control (P=0.035). During follow-up period, recurrence occurred in 10 (16.7%) patients in PWI (+) and 22 (36.7%) in control (P=0.02). The change in LAEF was not significantly different between the groups. On multivariate analysis, smaller LAV and additional PWI were independently associated with procedure outcome., Conclusions: PWI in addition to PVI plus linear lesions was an efficient strategy without deterioration of LA pump function in patients who underwent RFCA for PeAF., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Major adverse cardiovascular events (MACEs) in patients with or without cardiovascular disease (CVD) are greatly affected by various factors associated with metabolism and inflammation., Objective: To determine which clinical parameters at treatment are associated with the development of 2-year and 5-year MACEs in high-risk patients with CVD who have undergone drug-eluting stent (DES) implantation., Method: The present study involved a total of 432 patients who underwent percutaneous coronary intervention with DES. Variables representing the average and absolute amount of change in clinical parameters over the 12-month follow-up were assessed for association with 2-year and 5-year development of MACE. The study population was divided into quartiles for the variable showing the highest correlation to MACE development. Estimated incidence of 2-year and 5-year MACEs for each of the quartiles was determined by survival curve analysis, and subgroup analysis was performed for patients with diabetes and statin users., Results: Absolute change in fasting plasma glucose (FPG) over 12 months showed the highest correlation with 2-year and 5-year MACE development. The estimated incidence of MACE increased with increasing quartiles for absolute change in FPG. The association between absolute change in FPG and MACE development exhibited a stronger relationship for the specific subgroups of patients with diabetes and statin users. Increases and decreases in FPG had a comparable contribution to MACE development., Conclusion: A greater absolute change in FPG over 12 months post-PCI is an independent risk factor for 2-year and 5-year MACE development in DES-implanted patients, especially in the diabetes and statin users., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Fermented seafood is popular in Asian countries. This study examined the survival of feline calicivirus (FCV) and murine norovirus (MNV) during oyster fermentation. Oysters spiked with FCV and MNV were fermented with 5% or 10% salt at 18 °C for 15 days, and MNV and FCV titers, lactic acid bacteria (LAB) populations, pH, and enzymatic activity were measured at 0, 1, 3, 5, 7, 10, and 15 days post-fermentation (DPF). Reductions in MNV and FCV were greater in 5% NaCl-supplemented oysters than in 10% NaCl-supplemented oysters. In 5% NaCl oysters, MNV and FCV titers significantly decreased by 1.60 log and 3.01 log, respectively, at 15 DPF. Populations of LAB increased from 3.62 log10 colony-forming units/g at 0 DPF to 8.77 log10 colony-forming units/g at 15 DPF during oyster fermentation supplemented with 5% NaCl supplementation, and the pH decreased gradually from 5.38 at 0 DPF to 4.17 at 15 DPF. During oyster fermentation, α-amylase, proteinase, and lipase were produced at higher levels in 5% salted oysters than in 10% salted oysters (P < 0.01). We concluded that many of the antimicrobial factors produced in fermented oysters could contribute to a reduction in foodborne viruses., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: In contrast to many studies comparing everolimus-eluting stent (EES) with paclitaxel-eluting stent (PES), data directly comparing EES with sirolimus-eluting stent (SES) are limited, especially in patients with acute myocardial infarction (AMI)., Methods: This study includes 2911 AMI patients treated with SES (n=1264) or EES (n=1701) in Korea Acute Myocardial Infarction Registry (KAMIR). Propensity score matching was applied to adjust for baseline imbalance in clinical and angiographic characteristics, yielding a total of 2400 well-matched patients (1200 receiving SES and 1200 receiving EES). One-year clinical outcomes were compared between the two propensity score matched groups., Results: Baseline clinical and angiographic characteristics were similar between the two propensity score matched groups. One-year clinical outcomes of the propensity score matched cohort were comparable between the EES versus the SES groups including the rates of cardiac death (4.8% vs. 4.8%, P=1.000), recurrent myocardial infarction (1.4% vs. 1.7%, P=0.619), target lesion revascularization (1.4% vs. 1.6%, P=0.737), target lesion failure (7.0% vs. 7.3%, P=0.752), and probable or definite stent thrombosis (0.5% vs. 0.9%, P=0.224) except for a trend toward lower incidence of target vessel revascularization (1.9% vs. 3.0%, P=0.087) and a lower rate of total major adverse cardiac events (9.3% vs. 11.9%, P=0.034) in the EES group., Conclusions: The present propensity score matched analysis performed in a large-scale, prospective, multicenter registry suggests that the second-generation drug-eluting stent EES has at least comparable or even better safety and efficacy profiles as compared with SES in the setting of AMI., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objectives: This study sought to investigate the association of beta-blocker therapy at discharge with clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PCI)., Background: Limited data are available on the efficacy of beta-blocker therapy for secondary prevention in STEMI patients., Methods: Between November 1, 2005 and September 30, 2010, 20,344 patients were enrolled in nationwide, prospective, multicenter registries. Among these, we studied STEMI patients undergoing primary PCI who were discharged alive (n = 8,510). We classified patients into the beta-blocker group (n = 6,873) and no-beta-blocker group (n = 1,637) according to the use of beta-blockers at discharge. Propensity-score matching analysis was also performed in 1,325 patient triplets. The primary outcome was all-cause death., Results: The median follow-up duration was 367 days (interquartile range: 157 to 440 days). All-cause death occurred in 146 patients (2.1%) of the beta-blocker group versus 59 patients (3.6%) of the no-beta-blocker group (p < 0.001). After 2:1 propensity-score matching, beta-blocker therapy was associated with a lower incidence of all-cause death (2.8% vs. 4.1%, adjusted hazard ratio: 0.46, 95% confidence interval: 0.27 to 0.78, p = 0.004). The association with better outcome of beta-blocker therapy in terms of all-cause death was consistent across various subgroups, including patients with relatively low-risk profiles such as ejection fraction >40% or single-vessel disease., Conclusions: Beta-blocker therapy at discharge was associated with improved survival in STEMI patients treated with primary PCI. Our results support the current American College of Cardiology/American Heart Association guidelines, which recommend long-term beta-blocker therapy in all patients with STEMI regardless of reperfusion therapy or risk profile., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Although a large isolated surface area of the left atrium (LA) may improve the success rate of catheter ablation (CA) for paroxysmal atrial fibrillation (AF), little is known about the relation between clinical outcomes and the amount of atrial mass reduction (AMR: ratio of total isolated and ablated areas to LA surface area) in different ablation strategies for patients with long-standing persistent AF (L-PeAF)., Methods: We randomly assigned 119 consecutive L-PeAF patients to adjunctive linear ablation (n=60) or complex fractionated atrial electrogram (CFAE)-guided ablation (n=59) after circumferential antral pulmonary vein isolation (PVI). Linear lesions included roof and anterior lines with conduction block. LA defragmentation was performed with an automated CFAE-detection algorithm. Cavotricuspid isthmus block was performed in all patients. Creatine kinase-MB (CK-MB) and troponin-T levels were measured 1 day post-CA., Results: CK-MB and troponin-T levels were higher, ablation time was longer, and AMR was greater in the CFAE-guided ablation group than in the linear ablation group. AF termination during CA was more frequently observed in the linear ablation group than in the CFAE-guided ablation group (P=0.031). Twelve months after a single procedure, recurrence occurred in 16 (26.7%) patients with linear ablation and 27 (45.8%) patients with CFAE-guided ablation (P=0.023). On multivariate analysis, LA volume and ablation method were the only independent risk factors for arrhythmia recurrence., Conclusion: Conduction block through linear lines+PVI was an efficient ablation strategy for L-PeAF, whereas the AMR amount did not influence clinical outcomes., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Introduction: The gold standard for evaluating stent expansion after percutaneous coronary intervention (PCI) is intravascular ultrasound (IVUS). However, the routine use of this modality is costly and time consuming. StentBoost is a new imaging technique that improves fluoroscopy-based assessments of stent expansion. The purpose of this study was to evaluate the effect of StentBoost imaging-guided PCI on mid-term angiographic and clinical outcomes., Methods and Results: A total of 870 consecutive patients were recruited (mean age: 64.34 ± 11.61; men: 64.5%), all of whom underwent PCI with drug-eluting stents (DESs). The subjects were divided into a no StentBoost group (n=569 patients) and a StentBoost group (n=301 patients). The 6-month angiographic and 12-month clinical outcomes were compared between the two groups. At 1 month, clinical outcomes were similar between the two groups. At 6 months, the StentBoost group had significantly lower rates of late loss (0.32 ± 0.40 vs. 0.48 ± 0.59; p=0.005) and binary restenosis (1.2% vs. 8.3%; p=0.029) compared with the no-StentBoost group. At 12 months, StentBoost group had significantly lower the incidence of target lesion revascularization (TLR) (1.7% vs. 7%; p=0.034) and TLR-major adverse cardiac events (6% vs. 13.2%; p=0.037) compared with the no-StentBoost group., Conclusion: We conclude that the routine clinical use of StentBoost during PCI can be useful, and results in better medium-term angiographic and clinical outcomes., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Insulin resistance (IR) is known to be a risk factor for coronary artery disease (CAD). We aimed to evaluate the impact of IR on 1-year clinical outcomes in non-diabetic CAD patients who underwent percutaneous coronary intervention (PCI) with drug-eluting stents (DESs)., Methods and Results: A total of 229 consecutive non-diabetic CAD patients treated with DESs were enrolled. Study population was divided into IR group [homeostasis model assessment (HOMA) index ≥ 2.5, n=54] and non-IR group (HOMA index<2.5, n=175). Baseline clinical and procedural characteristics were similar between the groups except higher incidence of high-sensitivity C-reactive protein and lower incidence of multivessel disease as the target vessel in the non-IR group. There was a trend toward longer restenosis lesion length in the IR group at 6 months angiographic follow up but composite major clinical outcomes up to 1 year were similar between the two groups., Conclusions: Despite worse trend in angiographic outcomes in the IR group (HOMA index ≥ 2.5), it was not translated into worse 1-year major clinical outcomes following PCI with DESs as compared to the non-IR group., (Copyright © 2012 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

High-dose aspirin has been reported to aggravate coronary artery spasm (CAS). However, it is unknown whether low-dose aspirin (LDA; 100 mg) has deleterious impact on CAS. We assessed the impact of LDA on CAS induced by intracoronary acetylcholine (ACh) provocation test. A total of 2789 consecutive patients without significant coronary artery disease who underwent ACh test between November 2004 and March 2010 were enrolled. The patients were divided into two groups: the aspirin group taking LDA before ACh test (n=221) and the no aspirin group not taking aspirin (n=2568). At baseline, the prevalence of old age, diabetes mellitus, hypertension, and hyperlipidemia were higher in the aspirin group. During the ACh test, the incidence of significant CAS, ischemic chest pain, as well as severe and multivessel spasm was higher in the aspirin group. The response rate to lower ACh dose was higher in the aspirin group. Multivariate analysis showed that the previous use of LDA was an independent predictor of CAS (adjusted odds ratio, 1.6, 95% confidence interval, 1.0-2.3; p=0.031). However, it is likely that the association of LDA and CAS that we have observed is not causal but may be hypothesis generating due to significant baseline differences. Further, male gender, old age, lipid-lowering drugs, baseline spasm, and myocardial bridge were independent predictors of CAS. LDA was more frequently associated with CAS and ischemic symptoms, as well as severe and multivessel spasm, suggesting the patients who have received LDA would require more intensive medical therapies and close follow up., (Copyright © 2012 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Objectives: This study sought to compare everolimus-eluting stents (EES) with zotarolimus-eluting stents (ZES) in patients with acute myocardial infarction (AMI)., Background: There is a paucity of data to exclusively evaluate the safety and efficacy of second-generation drug-eluting stents (DES) in the setting of AMI., Methods: The present study enrolled 3,309 AMI patients treated with ZES (n = 1,608) or EES (n = 1,701) in a large-scale, prospective, multicenter registry-KAMIR (Korea Acute Myocardial Infarction Registry). Propensity score matching was applied to adjust for differences in baseline clinical and angiographic characteristics, producing a total of 2,646 patients (1,343 receiving ZES, and 1,343 receiving EES). Target lesion failure (TLF) was defined as the composite of cardiac death, recurrent nonfatal myocardial infarction, or target lesion revascularization. Major clinical outcomes at 1 year were compared between the 2 propensity score-matched groups., Results: After propensity score matching, baseline clinical and angiographic characteristics were similar between the 2 groups. Clinical outcomes of the propensity score-matched patients showed that, despite similar incidences of recurrent nonfatal myocardial infarction and in-hospital and 1-year mortality, patients in the EES group had significantly lower rates of TLF (6.5% vs. 8.7%, p = 0.029) and probable or definite stent thrombosis (0.3% vs. 1.6%, p < 0.001), compared with those in the ZES group. Furthermore, there was a numerically lower rate of target lesion revascularization (1.2% vs. 2.2%, p = 0.051) in the EES group than in the ZES group., Conclusions: In this propensity-matched comparison, EES seems to be superior to ZES in reducing TLF and stent thrombosis in patients with AMI., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Casuarinin is a naturally occurring tannin that is isolated from the leaves of Hippophae rhamnoides. It has been shown to have anti-oxidant, anti-cancer, anti-viral, and anti-inflammatory activities. The aim of this study was to investigate the possible mechanism by which casuarinin inhibits TNF-α/IFN-γ-induced Th2 chemokines expression in the human keratinocytes cell line HaCaT. We found that casuarinin suppressed TNF-α/IFN-γ-induced expression of TARC and MDC mRNA and protein in HaCaT cells. Casuarinin significantly inhibited TNF-α/IFN-γ-induced activation of NF-κB, STAT1, and p38 MAPK. Furthermore, we observed that p38 MAPK contributes to inhibition of TNF-α/IFN-γ-induced TARC and MDC production by blocking NF-κB and STAT1 activation in HaCaT cells. Taken together, these results suggest that casuarinin may exert anti-inflammatory responses by suppressing TNF-α/IFN-γ-induced expression of TARC and MDC via blockage of p38 MAPK activation and subsequent activation of NF-κB and STAT1. We propose that it could therefore be used as a therapeutic agent against inflammatory skin diseases., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Whether low molecular weight heparin (LMWH) enoxaparin is equivalent to unfractionated heparin (UFH) in patients with non-ST-segment elevation myocardial infarction (NSTEMI) undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES) remains unclear., Methods: A total of 2397 NSTEMI patients who underwent PCI with DES received either LMWH [n=1178, subcutaneous enoxaparin 1 mg/kg, b.i.d., initiated after the patient's arrival and continued until 3-5 days after PCI plus reduced dose of UFH (50-70 U/kg) during PCI] or UFH (n=1219, 24,000U/day infusion, initiated after the patient's arrival and continued until at least 48 h after PCI). The bleeding events and clinical outcomes during in-hospital and at 8 months were compared., Results: Enoxaparin group had similar incidences of cardiac death, total death, and total major adverse cardiac events (MACE) at 8 months compared with UFH group. The incidences of major and minor bleeding events were also similar between the two groups. Multivariable Cox regression analysis showed that enoxaparin group had similar incidences of cardiac death [adjusted odds ratio (OR) 1.16, 95% confidence interval (CI) 0.64-2.10, p=0.620], total death (adjusted OR 1.08, 95% CI 0.66-1.76, p=0.760), and total MACE (adjusted OR 0.94, 95% CI 0.69-1.28, p=0.692) at 8 months as compared with UFH group., Conclusions: Enoxaparin with reduced dose of UFH only during PCI as an adjunctive antithrombotic therapy in NSTEMI patients undergoing PCI with DES was safe and showed comparable 8-month clinical outcomes as compared with UFH alone., (Copyright © 2011 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: Coronary artery calcification (CAC) is correlated with aortic calcification (AC) and predicts coronary atherosclerosis as well as obstructive coronary artery disease (OCAD). This study aims to investigate whether AC predicts OCAD independent of CAC and its incremental value in predicting OCAD with CAC., Methods: Among the consecutive patients who underwent 64-slice multidetector CT (MDCT), we enrolled 120 stable OCAD (luminal narrowing ≥ 50%) patients and 120 controls without OCAD, matched for cardiovascular risk factors. CAC, thoracic AC, and OCAD were determined by MDCT., Results: The prevalence of AC and CAC were significantly higher in OCAD patients than in controls (64% vs. 48%, p = 0.019; 57% vs. 32%, p < 0.001, respectively). There is a significant correlation between AC and CAC scores in the overall study population (r = 0.528, p < 0.001). In univariate analysis, the odds ratios (ORs) of AC and CAC in predicting OCAD were 1.91 (95% CI, 1.14-3.21) and 2.82 (95% CI, 1.67-4.78), respectively. When an adjustment was made for each other, AC did not maintain a significant association with OCAD, whereas CAC persisted the association (OR, 2.52; 95% CI, 1.42-4.47). Both AC and CAC present as compared to both absent was found to be a more potent predictor for OCAD (OR, 3.37; 95% CI 1.78-6.36, p < 0.001) than CAC alone., Conclusions: The presence of AC was associated with stable OCAD independently from cardiovascular risk factors, but the association seemed to be based on the close correlation between AC and CAC. However, AC might have an incremental value with CAC for predicting OCAD., (Copyright © 2010. Published by Elsevier Ireland Ltd.)

Hippophae rhamnoides has been extensively used in oriental traditional medicines for treatment of asthma, skin diseases, gastric ulcers, and lung disorders. In this study, we isolated casuarinin from the leaves of H.rhamnoides and examined the effect of casuarinin on the TNF-α-induced ICAM-1 expression in a human keratinocytes cell line HaCaT. Pretreatment with casuarinin inhibited TNF-α-induced protein and mRNA expression of ICAM-1 and subsequent monocyte adhesiveness in HaCaT cells. Casuarinin significantly inhibited TNF-α-induced NF-κB activation. In addition, casuarinin inhibited activation of ERK and p38 MAPK in a dose-dependent manner. Furthermore, pretreatment with casuarinin decreased TNF-α-induced pro-inflammatory mediators, such as IL-1β, IL-6, IL-8, and MCP-1. These results demonstrated that casuarinin exerts its anti-inflammatory activity by suppressing TNF-α-induced expression of ICAM-1 and pro-inflammatory cytokines/chemokines via blockage of activation of NF-κB and ERK/p38 MAPK and can be used as a therapeutic agent against inflammatory skin diseases., (Copyright © 2011 Elsevier Inc. All rights reserved.)

We previously demonstrated that celastrol, a quinone methide triterpenoid derived from the medicinal plant Tripterygium wilfordii, exerts its anti-inflammatory activity through up-regulation of heme oxygenase-1 (HO-1) expression in the keratinocytes. In this study, we examined the signaling pathways that lead to the up-regulation of HO-1 expression by celastrol. In HaCaT cells, celastrol-induced HO-1 expression was dependent on ROS generation. ERK and p38 MAPK were major MAPK pathways responsible for celastrol-induced HO-1 expression. Celastrol induced Nrf2 activation. Nrf2 knockdown using small interfering RNA (siRNA) inhibited celastrol-induced HO-1 expression. Treatment with celastrol resulted in a marked increase in antioxidant response element (ARE)-driven transcriptional activity, which was dependent on ROS generation and activation of ERK and p38 MAPK. Furthermore, Nrf2 siRNA significantly reversed the inhibitory effect of celastrol on IFN-γ-induced expression of ICAM-1 in the keratinocytes. Taken together, our results indicate that celastrol can activate the ROS-ERK/p38-Nrf2-ARE signaling cascades leading to the up-regulation of HO-1 which is partly responsible for its anti-inflammatory activity in the keratinocytes., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Depression is a risk factor for the development of coronary heart disease but the relationship between coronary endothelial dysfunction and depression is not yet known. This study investigated whether depressive symptomatology is associated with coronary endothelial dysfunction in patients without coronary artery disease (CAD)., Methods and Results: Incremental acetylcholine (Ach; 20, 50 and 100 microg/min) and nitrate (200 microg/min) were infused into the left coronary ostium of 52 patients (male 30, 51.8 years) with depressive symptoms as indicated by a Beck Depression Inventory (BDI) score of >or=10 and a Hamilton Depression Rating Scale (HAM-D17) of >or=7 but without overt CAD or any vasoactive medications. Vascular responses to each drug were measured quantitatively at the mid-segments of the left anterior descending artery (LAD) and compared to those of 103 matched control subjects (male 64, 51.3 years) with angiographically normal looking LAD and as estimated by BDI <10 and HAM-D17 <7. Patients in the depressive group showed significant vasoconstriction compared with patients in the non-depressive group (p=0.017, 0.090, 0.004 respectively). However, endothelium-independent vasodilatation to nitrates did not differ significantly between the two groups (p=0.461). No differences in risk factors were found between the two groups., Conclusions: Depressive mood is associated with coronary endothelial dysfunction in patients without CAD, suggesting a possible mechanism by which depressive mood may act as a cardiovascular risk factor., (Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.)