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Utilizing COsub2/subas one of the monomer resources, poly(vinylcyclohexene carbonates) (PVCHCs) are used as the precursor for preparing cationic PVCHCs (CPVCHCs) via thiol-ene click functionalization. Through the functionalization, CPVCHC-43 with a tertiary amine density of 43% relative to the backbone is able to display a significantly antibacterial ability against Staphylococcus aureus (S. aureus). Blending CPVCHC-43 with polyacrylonitrile (PAN), CPVCHC/PAN nanofiber meshes (NFMs) have been successfully prepared by electrospinning. More importantly, two crucial fibrous structural factors including CPVCHC/PAN weight ratio and fiber diameter have been systematically investigated for the effects on the antibacterial performance of the NFMs. Sequentially, a quaternization treatment has been employed on the NFMs with an optimal fibrous structure to enhance the antibacterial ability. The resulting quaternized NFMs have demonstrated the great biocidal effects against Gram-positive and Gram-negative bacteria. Moreover, the excellent biocompatibility of the quaternized NFMs have also been thoroughly evaluated and verified.

Rationale: The major cause of heart failure is myocardium death consequent to detrimental cardiac remodeling and fibrosis following myocardial infarction. The cardiac protective cytokine interleukin (IL)-33, which signals by ST2 receptor binding, is associated with group 2 innate lymphoid cell (ILC2) activation and regulates tissue homeostasis and repair following tissue injury in various tissues. However, the distribution and role of IL-33-responsive ILC2s in cardiac fibrosis remain unclear. In this study, we elucidated the roles of IL-33-responsive cardiac-resident ILC2s and IL-33-mediated immunomodulatory functions in cardiac fibrosis. Methods: We examined the distribution of cardiac ILC2s by using flow cytometry. The roles of IL-33-mediated ILC2 expansion in cardiac fibrosis was evaluated in the mouse model of catecholamine-induced cardiac fibrosis. ILC-deficient Rag2‒/‒IL2Rγc‒/‒ mice were implemented to determine the contribution of endogenous ILC in the progression of cardiac fibrosis. Histopathological assessments, speckle tracking echocardiography, and transcriptome profile analysis were performed to determine the effects of IL-33-mediated cardiac protective functions. Results: We identified the resident cardiac ILC2s, which share similar cell surface marker and transcriptional factor expression characteristics as peripheral blood and lung tissue ILC2s. IL-33 treatment induced ILC2 expansion via ST2. In vivo, ILC-deficient Rag2‒/‒IL2Rγc‒/‒ mice developed exacerbated cardiac fibrosis following catecholamine-induced stress cardiac injury. IL-33 treatment expanded cardiac ILC2s and revealed protective effects against cardiac tissue damage with reduced cardiomyocyte death, immune cell infiltration, tissue fibrosis, and improved myocardial function. Transcriptome analysis revealed that IL-33 attenuated extracellular matrix synthesis- and fibroblast activation-associated gene expressions. IL13-knockout or epidermal growth factor receptor (EGFR) inhibition abolished IL-33-mediated cardiac protective function, confirming IL-13 and EGFR signaling as crucial for IL-33-mediated cardioprotective responses. Moreover, ILC2-produced BMP-7 served as a novel anti-fibrotic factor to inhibit TGF-β1-induced cardiac fibroblast activation. Conclusion: Our findings indicate the presence of IL-33-responsive ILC2s in cardiac tissue and that IL-33-mediated ILC2 expansion affords optimal cardioprotective function via ILC2-derived factors. IL-33-mediated immunomodulation is thus a promising strategy to promote tissue repair and alleviate cardiac fibrosis following acute cardiac injury.

Pancreatic cancer is an aggressive malignancy associated with poor prognosis and a high tendency in developing infiltration and metastasis. K-ras mutation is a major genetic disorder in pancreatic cancer patient. RNAi-based therapies can be employed for combating pancreatic cancer by silencing K-ras gene expression. However, the clinical application of RNAi technology is appreciably limited by the lack of a proper siRNA delivery system. To tackle this hurdle, cationic poly (cyclohexene carbonate) s (CPCHCs) using widely sourced CO2 as the monomer are subtly synthesized via ring-opening copolymerization (ROCOP) and thiol-ene functionalization. The developed CPCHCs could effectively encapsulate therapeutic siRNA to form CPCHC/siRNA nanoplexes (NPs). Serving as a siRNA carrier, CPCHC possesses biodegradability, negligible cytotoxicity, and high transfection efficiency. In vitro study shows that CPCHCs are capable of effectively protecting siRNA from being degraded by RNase and promoting a sustained endosomal escape of siRNA. After treatment with CPCHC/siRNA NPs, the K-ras gene expression in both pancreatic cancer cell line (PANC-1 and MiaPaCa-2) are significantly down-regulated. Subsequently, the cell growth and migration are considerably inhibited, and the treated cells are induced into cell apoptotic program. These results demonstrate the promising potential of CPCHC-mediated siRNA therapies in pancreatic cancer treatment.

Background and aim Antibiotic prophylaxis should be instituted for cirrhotic patients with upper gastrointestinal bleeding (UGIB), but the benefit on compensated patients remains undetermined. We aimed to compare the clinical outcomes between cirrhotic patients without major complications with UGIB with and without antibiotic prophylaxis. Methods We conducted this population-based cohort study by using Taiwanese Longitudinal Health Insurance Database 2000 (LHID2000, between 1997 to 2013), aged 18 years or older with a hospital discharge diagnosis of cirrhosis (n = 64,506), UGIB (n = 7,784), and endoscopic therapy (n = 2,292). After strict exclusions, 1205 patients were enrolled and were divided into antibiotic exposure (n = 558) and non-exposure (n = 647) groups. The outcomes were rebleeding and mortality. Results After completing the analysis adjusted by death, the rebleeding rates within 4 weeks were significantly lower in patients with antibiotic prophylaxis (3.05% versus 6.03%, P = 0.0142) and those with endoscopic therapy (0.72% vs 3.09%, P = 0.0033) but not significant after 3 months and onwards. Male patients aged > 55, high CCI score ≧ 4, and UGIB of variceal etiologies were benefited from rebleeding. The use of antibiotics did not significantly impact 6-week mortality (adjusted hazard ratio: 1.07, 95%CI: 0.41~2.75; P = 0.8943). Old age, multiple comorbidities, and UGIB of variceal etiologies were risk factors of all-cause mortality. Conclusions The current study suggested that cirrhotic patients without major complications who suffered from UGIB were benefited by the use of antibiotics to prevent rebleeding within 4 weeks after endoscopic treatment of UGIB especially for those with age > 55, high CCI score ≧ 4, and UGIB of variceal etiologies.

Summary Background Cardiac implantable electronic device (CIED) infection, a major complication of a CIED implant procedure, can prolong hospitalization and cause mortality. Aim To evaluate the efficacy of a bundled skin antiseptic preparation for preventing infection after implantation of a complex CIED. Methods This study analysed 1163 consecutive patients who had received a bundled skin antiseptic preparation before CIED implantation from July 2012 to December 2017. According to the complexity of the CIED implant procedure, the patients were divided into a complex CIED group (N = 370) and a non-complex CIED group (N = 793). A complex procedure was defined as a pacemaker replacement, implantation of implantable cardioverter defibrillator and cardiac resynchronization therapy, device upgrade, or lead revision. Findings During a mean follow-up of 2.9 ± 1.7 years, CIED infection developed in 15 patients (1.3%), and the incidence of minor and major infection was 1.1% and 0.2%, respectively. The incidence of CIED infection did not significantly differ between the complex CIED group and the non-complex CIED group (1.1% vs 1.4%, respectively; non-significant). Multivariate analysis indicated that procedural complexity was not an independent predictor of CIED infection. After 2:1 propensity score matching, the matched non-complex CIED group and the matched complex CIED group still showed no significant difference in the incidence of CIED infection. Conclusion Bundled skin antiseptic preparation is an effective and widely applicable strategy for decreasing infection risk after a complex CIED implantation.

AIMS Pulmonary vein isolation (PVI) is an effective procedure for atrial fibrillation (AF). The role of additional cavotricuspid isthmus (CTI) block ablation remains controversial in AF patients without atrial flutter (AFL). Therefore, this study aimed to explore the clinical outcome of additional CTI block ablation in patients without AFL. METHODS Between January 2013 and December 2017, a total of 139 patients who did not have documented AFL and who underwent catheter ablation for AF were recruited. Fifty-seven patients were classified in additional CTI block ablation group and 82 patients were classified in without CTI group. The incidence of early-onset and late-onset atrial arrhythmia recurrence was compared between the two groups. RESULTS The additional CTI group had a higher prevalence of persistent or long-standing AF and larger left atrial volume. The additional CTI group had a higher incidence of late-onset atrial arrhythmia recurrence (38.6% vs 12.2%; P

Background Endocardial late fractionated potentials during sinus rhythm mapping may reflect abnormal "subendocardial" substrates associated with right ventricular outflow tract (RVOT) ventricular arrhythmias (VAs). The aim of this study was to explore the clinical outcomes of catheter ablation guided by these late fractionated potentials for RVOT VAs in patients without structural heart disease. Methods From January 2016 to March 2018, 28 patients underwent catheter ablation for RVOT premature ventricular contractions (PVCs) or ventricular tachycardia (VT), guided by the EnSite NavX or Velocity V5.0 three-dimensional mapping system (Abbott, St. Paul, MN, USA). Among them, 10 patients (35.7%) were found to have endocardial late fractionated potentials during sinus rhythm mapping (Group 1). Group 2 was composed of 18 patients in whom no endocardial late fractionated potentials were seen. The burden of VAs, acute procedural success, and 3-month clinical outcomes were analyzed. Results The average duration of late fractionated potentials after the end of QRS during sinus rhythm mapping in group 1 was 45.00 ± 17.15 ms. Baseline demographics and morphology and burden of PVCs were similarly distributed between both groups. Group 1 had higher acute procedural success compared to group 2 (100% vs 66.7%; P = .039). Moreover, at 3-month follow-up, group 1 had lower total PVCs (49 (1-5986) versus 4316 (1-23231); P = .048), PVC burden (0% (0-5.9) vs 4.3% (0-18.9); P = .055), and higher clinical success (100% vs 55.6%; P = .025) compared to group 2. Conclusion The identification and elimination of endocardial late fractionated potentials during sinus rhythm mapping could improve the acute success and short-term outcomes of ablation for RVOT VAs.

Background The association of postimplant tricuspid regurgitation (TR) and heart failure (HF) hospitalization in patients without HF and preexisting abnormal TR and TR pressure gradient (PG) remain unclear. Hypothesis This study aimed to explore the clinical outcomes of progressive postimplant TR after permanent pacemaker (PPM) implantation. Methods A total of 1670 patients who underwent a single ventricular or dual‐chamber transvenous PPM implantation at our hospital between January 2003 and December 2017 were included in the study. Patients with prior valvular surgery, history of HF, and baseline abnormal TR and TRPG were excluded. Finally, a total of 1075 patients were enrolled in this study. Progressive TR was defined as increased TR grade of ≥2 degrees and TRPG of >30 mmHg after implant. Results In 198 (18.4%) patients (group 1) experienced progressive postimplant TR and elevated TRPG, whereas 877 patients (group 2) did not have progressive postimplant TR. Group 1 had larger change in postimplant TRPG (group 1 vs. group 2; 12.8 ± 9.6 mmHg vs. 1.1 ± 7.6 mmHg; p

Background Cardiovascular disease is the most common cause of death in patients with rheumatoid arthritis. It is believed that using disease‐modifying antirheumatic drugs (DMARDs) to control inflammation can reduce the risk of cardiovascular disease. In this study, we investigated whether patients who responded differently to DMARDs might sustain different cardiovascular events. Methods and Results We designed a cohort study using the Chang Gung Research Database. We identified 7114 patients diagnosed with rheumatoid arthritis. After strict exclusion criteria, we collected 663 individuals as an inadequate response to DMARDs group. Then, 2034 individuals were included as the control group. The end point was composite vascular outcomes, including acute coronary syndrome or ischemic stroke. We used the inverse probability of treatment weighting to keep the covariates between these 2 groups well balanced. We compared the risk of these outcomes using the Cox proportional hazards model. The mean follow‐up time was 4.7 years. During follow‐up, there were 7.5% and 6.4% of patients with composite vascular outcomes in the DMARD‐inadequate response and control groups, respectively. There was no significant difference in the risk of composite vascular outcomes (95% CI, 0.94–1.41) and ischemic stroke (95% CI, 0.84–1.36). The risk of acute coronary syndrome was significantly higher in the DMARD‐inadequate response group (hazard ratio, 1.45; 95% CI, 1.02–2.05). Conclusions Patients with DMARD‐inadequate response rheumatoid arthritis have a higher risk of developing acute coronary syndrome than those whose disease can be controlled by DMARDs.

BackgroundThe association of post-implant tricuspid regurgitation (TR) and heart failure (HF) hospitalization in patients without HF and preexisting abnormal TR and TR pressure gradient (PG) remain unclear. This study aimed to explore the clinical outcomes about progressive post-implant TR after permanent pacemaker (PPM) implantation.Methods A total of 1,670 patients who underwent a single ventricular or dual-chamber transvenous PPM implantation at our hospital between January 2003 and December 2017 were included in the study. Patients with prior valvular surgery, heart failure (HF), and baseline abnormal TR and TRPG were excluded. Finally, a total of 1,075 patients were enrolled in this study. Progressive TR was defined as increased TR grade of ≥2 degrees and/or TRPG of >30 mmHg after implant.Results198 (18.4%) patients (group 1) experienced progressive post-implant TR and/or elevated TRPG. Group 1 had l larger changes in post-implant TRPG (group 1 vs. group 2; 12.8 ± 9.6 mmHg vs. 1.1 ± 7.6 mmHg; p < 0.001) than group 2 without progressive post-implant TR. Group 1 had a higher incidence of HF hospitalization compared to group 2 (13.6% vs. 4.7%; p < 0.001). Pre-implant TRPG (HR: 1.075; 95% confidence interval (CI): 1.032-1.121; p = 0.001) and post-implant left atrial dimension (HR: 1.076; 95% CI: 1.038-1.114; p < 0.001) were independent predictors of progressive post-implant TR. ConclusionsAfter a transvenous ventricular-based PPM implantation, 18.4% of patients experienced progressive post-implant TR and/or elevated TRPG. Higher pre-implant TRPG and larger post-implant LA dimension were independent predictors of progressive post-implant TR.

The relationship between left ventricular ejection fraction (LVEF) and cardiovascular (CV) outcome is documented in patients with low LVEF. Ventilatory inefficiency is an important prognostic predictor. We hypothesized that the presence of ventilatory inefficiency influences the prognostic predictability of LVEF in heart failure (HF) outpatients. In total, 169 HF outpatients underwent the cardiopulmonary exercise test (CPET) and were followed up for a median of 9.25 years. Subjects were divided into five groups of similar size according to baseline LVEF (&le, 39%, 40&ndash, 58%, 59&ndash, 68%, 69&ndash, 74%, and &ge, 75%). The primary endpoints were CV mortality and first HF hospitalization. The Cox proportional hazard model was used for simple and multiple regression analyses to evaluate the interrelationship between LVEF and ventilatory inefficiency (ventilatory equivalent for carbon dioxide (VE/VCO2) at anaerobic threshold (AT) &gt, 34.3, optimized cut-point). Only LVEF and VE/VCO2 at AT were significant predictors of major CV events. The lower LVEF subgroup (LVEF &le, 39%) was associated with an increased risk of CV events, relative to the LVEF &ge, 75% subgroup, except for patients with ventilatory inefficiency (p = 0.400). In conclusion, ventilatory inefficiency influenced the prognostic predictability of LVEF in reduced LVEF outpatients. Ventilatory inefficiency can be used as a therapeutic target in HF management.

Atrial fibrillation (AF) is an important complication of acute myocardial infarction (AMI). The association between AF and serum lipid profile is unclear and statin use for lowering the incidence of new-onset AF remains controversial. The objective of this study was to investigate whether statins confer a beneficial effect on AF after AMI. Data available in the Taiwan National Health Insurance Research Database on 32886 AMI patients between 2008 and 2011 were retrospectively analyzed. Total 27553 (83.8%) had complete 1-yr follow-up data. Cardiovascular outcomes were analyzed based on the baseline characteristics and AF type (existing, new-onset, or non-AF). AF groups had significantly higher incidence of heart failure (HF), stroke, all-cause death, and major adverse cardiac and cerebrovascular event (MACCE) after index AMI (all P

Background and Objectives: Non-selective &beta, blockers (NSBB) could prevent decompensation and hepatocellular carcinoma (HCC) in cirrhotic patients with clinically significant portal hypertension (CSPH), but remained uncertain for compensated cirrhotic patients without major complications. We aimed to compare the clinical outcomes between propranolol users and non-users of a CC group without major complications. Material and Methods: We conducted this population-based cohort study by using the Taiwanese Longitudinal Health Insurance Database 2000. Propranolol users (classified as cumulative defined daily dose (cDDD)) and non-PPL users were matched with a 1:1 propensity score in both cohorts. Results: This study comprised 6896 propranolol users and 6896 non-propranolol users. There was no significant impact on the development of spontaneous bacterial peritonitis between the two groups (aHR: 1.24, 95% confidence interval (CI): 0.88~1.75, p = 0.2111). Male gender, aged condition, and non-liver related diseases (peripheral vascular disease, cerebrovascular disease, dementia, pulmonary disease, and renal disease) were the independent risk factors of mortality. PPL users had significantly lower incidence of HCC development than non-users (aHR: 0.81, p = 0.0580, aHR: 0.80, p = 0.1588, and aHR: 0.49, p &lt, 0.0001 in the groups of 1&ndash, 28, 29&ndash, 90, and &gt, 90 cDDD, respectively). Conclusion: The current study suggested that high cumulative doses of propranolol could decrease the risk of hepatocellular carcinoma among compensated cirrhotic patients without major complications. Further large-scale prospective studies are still required to confirm the findings in this study. Results: It remained uncertain whether non-selective &beta, blockers (NSBB) could prevent decompensation and hepatocellular carcinoma (HCC) in compensatory cirrhotic patients without major complications. This study aimed to compare the clinical outcomes between propranolol users and non-users of the CC group without major complications.

BACKGROUND AND AIMS Colonoscopic polypectomy in end-stage renal disease (ESRD) patients are at risks of post-polypectomy bleeding and perforation, but evidences are limited. This study aimed to determine the incident polypectomy complications among ESRD patients. METHODS In the nationwide ESRD cohort, a propensity score matched case-control study design was conducted to assess risk associated with post-polypectomy bleeding and perforation using the Taiwanese National Health Insurance Research Database from 1997 to 2013 for adults aged 40 years and older; 7011 ESRD and 19 118 non-ESRD patients met the study criteria. A total of 5302 patients in each group were matched for further analyses. The primary endpoint was post-polypectomy bleeding or bowel perforation in 30 days. The secondary endpoint was mortality and length of hospital stay for the bleeding complications requiring hospitalization. RESULTS Overall incidences of post-polypectomy bleeding or perforation in patients with ESRD was higher than the non-ESRD group (5.83% vs 1.78%, P

The purpose of this population-based case&ndash, control study was to clarify the impact of cumulative dosage of nonsteroidal anti-inflammatory drugs (NSAIDs) on recurrent peptic ulcers among chronic users after Helicobacter pylori (H. pylori) eradication. We analyzed data of 203,407 adult peptic ulcer disease (PUD) patients from the National Health Insurance Research Database in Taiwan entered between 1997 and 2013. After matching for age/gender frequencies and the length of follow-up time in a ratio of 1:1, the matched case&ndash, control groups comprised 1150 patients with recurrent PUD and 1150 patients without recurrent PUD within 3 years of follow-up. More recurrent PUDs occurred in NSAID users than in the control group (75.30% versus 69.74%, p = 0.0028). Independent risk factors for recurrent PUD included patients using NSAIDs (adjusted OR (aOR): 1.34, p = 0.0040), H. pylori eradication (aOR: 2.73, p &lt, 0.0001), concomitant H2 receptor antagonist (aOR: 1.85, 0.0001) and anti-coagulant (aOR: 4.21, p = 0.0242) use. Importantly, in the initial subgroup analysis, the risk ratio of recurrent PUD did not increase in NSAID users after H. pylori eradication compared with that in non-users (p = 0.8490) but a higher risk for recurrent PUD with the increased doses of NSAIDs without H. pylori eradication therapy (aOR: 1.24, p = 0.0424, aOR: 1.47, p = 0.0074, and aOR: 1.64, p = 0.0152 in the groups of &le, 28, 29&ndash, 83, and &ge, 84 cumulative defined daily doses, respectively). The current study suggested that H. pylori eradication therapy could decrease the risk of recurrent PUD among patients with high cumulative doses of NSAIDs.

BACKGROUND: Controlling modifiable risk factors (MRFs) in patients with cardiovascular diseases has been shown to be effective in reducing re-hospitalization rates. The aim of this study was to investigate the rates of controlled MRFs and clinical outcomes after pharmacist interventions in patients with myocardial infarction (MI) after hospital discharge. METHODS: This prospective randomized clinical study was conducted at one medical center in Taiwan, and enrolled patients with MI from January 1, 2012 to December 31, 2014. Patients received medication reconciliation and education from a pharmacist before hospital discharge. The intervention group (IG) received continuous consultations from the pharmacist after discharge, whereas the control group (CG) did not. Primary outcomes included achieving blood pressure < 140/70 mmHg, low-density lipoprotein-cholesterol (LDL-C) < 70 mg/dL, and hemoglobin A1c (HbA1c) < 7% targets. The secondary outcome was major adverse cardiac events (MACEs), defined as re-hospitalization due to MI, unstable angina and stroke. RESULTS: Two hundred and eight patients completed the study protocol (106 in the IG and 102 in the CG). The rate of achieving blood pressure goal was similar between the two groups. More patients in the IG achieved LDL-C and HbA1c goals than those in the CG at 1 year and 2 years post discharge. However, there was no significant difference in the cumulative incidence of MACEs between the two groups (5.7% vs. 9.8%) (p = 0.262). Diabetes was the only independent predictor of re-hospitalization due to a MACE. CONCLUSIONS: Pharmacist interventions led to a higher rate of optimal controlled MRFs but did not significantly reduce the MACE rate in the patients with MI.

Hyperglycaemia causes endothelial dysfunction, which is the initial process in the development of diabetic vascular complications. Upon injury, endothelial cells undergo an endothelial-to-mesenchymal transition (EndMT), lose their specific marker, and gain mesenchymal phenotypes. This study investigated the effect of liraglutide, a glucagon-like peptide 1 (GLP-1) receptor agonist, on EndMT inhibition and neointima formation in diabetic mice induced by streptozotocin. The diabetic mice with a wire-induced vascular injury in the right carotid artery were treated with or without liraglutide for four weeks. The degree of neointima formation and re-endothelialisation was evaluated by histological assessments. Endothelial fate tracing revealed that endothelium-derived cells contribute to neointima formation through EndMT in vivo. In the diabetic mouse model, liraglutide attenuated wire injury-induced neointima formation and accelerated re-endothelialisation. In vitro, a high glucose condition (30 mmol/L) triggered morphological changes and mesenchymal marker expression in human umbilical vein endothelial cells (HUVECs), which were attenuated by liraglutide or Activin receptor-like 5 (ALK5) inhibitor SB431542. The inhibition of AMP-activated protein kinase (AMPK) signaling by Compound C diminished the liraglutide-mediated inhibitory effect on EndMT. Collectively, liraglutide was found to attenuate neointima formation in diabetic mice partially through EndMT inhibition, extending the potential therapeutic role of liraglutide.

Infective endocarditis (IE) is a severe disease with a hospital mortality rate of 17&ndash, 25%. Early identification of IE patients with high risk of mortality may improve their clinical outcomes. Patients with diabetes mellitus (DM) who develop infective diseases are associated with worse outcomes. This study aimed to define the impact of DM on long-term mortality in IE patients. A total of 412 patients with definite IE from February 1999 to June 2012 were enrolled in this observational study and divided into 2 groups: group 1, patients with DM (n = 72) and group 2, patients without DM (n = 340). The overall in-hospital mortality rate for both groups combined was 20.2% and was higher in group 1 than in group 2 (41.7% vs. 16.5%, p &lt, 0.01). Compared to patients without DM, patients with DM were older and associated with higher incidence of chronic diseases, less drug abuse, higher creatinine levels, and increased risk of Staphylococcus aureus infection (all p &lt, 0.05). Moreover, they were more likely to have atypical clinical presentation and were associated with longer IE diagnosis time (all p &lt, 0.05). In multivariable analysis, DM is an independent and significant predictor of mortality. The prognosis of IE patients with DM is still poor. Early identification and more aggressive treatment may be considered in IE patients with DM.

We investigated the accuracy of various bleeding risk scores to estimate the bleeding risk in patients with acute myocardial infarction (AMI) managed with percutaneous coronary intervention (PCI) access via the radial artery.We retrospectively enrolled 1,651 patients who were definitively diagnosed with ST-elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI). We assessed the predictive validities of 30-day bleeding events in various scoring systems using receiver operating characteristic curves.Overall, ACUITY-HORIZONS exhibited the highest area under the curve to predict 30-day bleeding, followed by ACTION and CRUSADE; HAS-BLED displayed the lowest score. With a cut-off of 17, ACUITY-HORIZONS demonstrated the best discrimination for the Thrombolysis in Myocardial Infarction (TIMI) 30-day serious bleeding rate. We observed significant differences among all-cause death, cardiovascular death, and major adverse cardiac events between the ACUITY-HORIZONS groups with a score of ≤ 17 and > 17. ACUITY-HORIZONS score > 17, initial systolic blood pressure (SBP) < 90 mmHg, and Killip III and IV upon admission positively predicted the 30-day bleeding risk, whereas myocardial infarction (MI) and TIMI major bleeding within 30 days, heart failure at admission, and initial SBP < 90 mmHg positively predicted the 30-day mortality.Comparatively, ACUITY-HORIZON is the most reliable system in predicting 30-day bleeding for patients with AMI via transradial PCI. In the transradial scenario, bleeding and MI within 30 days are substantially related to 30-day mortality.

AIMS Catheter ablation has become an effective treatment modality for atrial fibrillation (AF). However, the relationship between common pulmonary vein (PV) and recurrent atrial tachyarrhythmia (ATA) after PV isolation (PVI) remains controversial. This study aimed to explore the function of common PV on the risk of recurrent ATA after PVI. METHODS We identified a total of 191 patients who received radiofrequency catheter ablation for paroxysmal AF at our hospital between July 2010 and December 2017 for retrospective chart review. We collected the following data for analysis: results of preprocedural computed tomography, including the anatomy of PV and left atrial (LA) volume; the incidence of early- and late-onset recurrence of ATA. We compared these characteristics between the two groups defined by the presence or absence of the late-onset recurrence of ATA. RESULTS Compared to the no ATA recurrence group, the ATA recurrence group had larger LA size, larger LA end-diastolic and systolic volumes, larger maximal diameter of PV, higher prevalence of common PV, and higher incidence of early-onset recurrence of ATA. In multivariate logistic regression analyses, presence of common PV and early-onset recurrence were independently associated with late-onset recurrence of ATA. Compared to patients without common PV, patients with common PV had larger diameter of PV and higher incidence of late-onset recurrent ATA. CONCLUSION In patients with paroxysmal AF, early-onset recurrence of ATA and the presence of common PV were independently associated with late-onset recurrent ATA after radiofrequency catheter ablation.

This study investigated the efficacy and safety of ticagrelor compared with clopidogrel in patients with end-stage renal disease (ESRD) and acute myocardial infarction (AMI). We retrospectively enrolled patients who had received regular dialysis and had undergone percutaneous coronary intervention (PCI) for AMI at our hospital between January 2013 and December 2016. Outcomes analyzed included cardiovascular death, death from any cause, MI, stroke, and bleeding events. Patients were allocated to the ticagrelor group (N = 74) or the clopidogrel group (N = 116) according to the treatment they had received. No statistically significant differences were found between the groups in terms of in-hospital primary endpoint (composite of cardiovascular death, MI, and stroke: 12.2% and 15.5% for ticagrelor and clopidogrel, respectively; p = 0.518), secondary endpoint, or any bleeding events (39.2 vs. 34.5%; p = 0.511). No statistically significant differences were found for the 1-year primary endpoint (p = 0.424), secondary endpoint, and any bleeding events (p = 0.663). Risk factors for in-hospital cardiovascular death were shock and cardiopulmonary resuscitation at initial AMI presentation, lack of beta-blocker use, and in-hospital gastrointestinal bleeding. Risk factors for 1-year cardiovascular death were shock at initial AMI presentation and lack of beta-blocker use. Only respiratory failure was a risk factor for in-hospital and 1-year gastrointestinal bleeding. In patients with ESRD and AMI, ticagrelor resulted in numerically fewer but statistically nonsignificant rates of in-hospital and 1-year cardiovascular events with no significant increase in bleeding events compared with clopidogrel.

Background Although angioembolization increases the success rate of non-operative management in patients with blunt splenic injuries (BSI), the issue of contrast-induced nephropathy (CIN) due to serial administration of contrast medium remains unclear. We aimed to examine the risk factors of CIN and their clinical effect on mortality in patients with BSI. Method We retrospectively studied the complete data on 377 trauma patients with BSI who survived more than 48 h between July 2003 and June 2015. CIN was defined as the relative (≥25%) or absolute (≥0.5 mg/dL) increase in serum creatinine within 48 h after contrast administration. A multivariate logistic regression analysis was conducted to identify the independent predictors of CIN and mortality. Results CIN was independently associated with body mass index (BMI) ≥ 30 kg/m 2 (odds ratio [OR]: 3.25, 95% confidence interval [CI]: 1.20–8.76), injury severity score (ISS) ≥ 25 (OR: 6.08, 95% CI: 2.76–13.53), and 24-h hemoglobin (Hb) Conclusion In this study, we found that BMI ≥ 30 kg/m 2 , ISS ≥ 25, and 24-h Hb

We tested the hypothesis that transfusion of autologous peripheral blood-derived endothelial progenitor cells (PBDEPC) via the internal carotid artery could reduce brain-infarct zone (BIZ) and neurological deficit in rats following acute ischemic stroke (IS) induced by 50-min left middle cerebral artery occlusion.Adult male Sprague-Dawley rats (n=60) were equally divided into group 1 [sham control (SC)], group 2 [SC-PBDEPC (5.7 × 10(6)/kg)], group 3 (IS), group 4 [IS-low-dose PBDEPC (1.7 × 10(6)/kg)], group 5 [IS-high-dose PBDEPC (5.7×10(6)/kg)]. Groups 2 to 5 received G-CSF (35 μg/kg subcutaneously) for 4 days before drawing blood for PBDEPC culture.By day 90, BIZ determined by histopathology (area) and brain MRI (volume) were highest in group 3, lowest in groups 1 and 2, higher in group 4 than in group 5 (all p0.0001), and not significantly different between groups 1 and 2. Sensorimotor functional results exhibited an opposite pattern of BIZ among groups 3 to 5 (p0.005). Angiogenesis biomarkers (SDF-1α, CXCR4, VEGF, angiopoietin-1) significantly increased progressively from groups 1 and 2 to group 5 (all p0.0001). Oxidative-stress (NOX-1, NOX-2, oxidized protein), apoptotic (cleaved caspase 3 and PARP, mitochondrial Bax), inflammatory (MMP-9, TNF-α, AQP-4, GFAP, iNOS), and brain-damaged (cytosolic cytochrome-C) biomarkers showed an identical pattern, whereas anti-inflammatory (Bcl-2), mitochondrial preservation (mitochondrial cytochrome-C, PGC-1α), and endothelial function (CD31+, vWF+, eNOS) biomarkers, and vessel density showed an opposite pattern of BIZ among these five groups (all p0.001).Higher-dose was superior to lower-dose EPC treatment for reducing BIZ and improving neurological functional outcome.

Background: Diabetic cardiomyopathy (DCM) is characterized by cardiac fibrosis and stiffness, which often develops into heart failure. This study investigated the role of Ras protein-specific guanine nucleotide releasing factor 1 (RasGRF1) in the development of DCM. Methods: Forty-eight mice were divided into four groups (n = 12 per group): Group 1: Wild-type (WT) mice, Group 2: RasGRF1 deficiency (RasGRF1&minus, /&minus, ) mice. Group 3: Streptozotocin (STZ)-induced diabetic WT mice, Group 4: STZ-induced diabetic RasGRF1&minus, mice. Myocardial functions were assessed by cardiac echography. Heart tissues from all of the mice were investigated for cardiac fibrosis, inflammation, and oxidative stress markers. Results: Worse impaired diastolic function with elevation serum interleukin (IL)-6 was found in the diabetic group compared with the non-diabetic groups. Serum IL-6 levels were found to be elevated in the diabetic compared with the non-diabetic groups. However, the diabetic RasGRF1&minus, mice exhibited lower serum IL-6 levels and better diastolic function than the diabetic WT mice. The diabetic RasGRF1&minus, mice were associated with reduced cardiac inflammation, which was shown by lower invading inflammation cells, lower expression of matrix metalloproteinase 9, and less chemokines compared to the diabetic WT mice. Furthermore, less oxidative stress as well as extracellular matrix deposition leading to a reduction in cardiac fibrosis was also found in the diabetic RasGRF1&minus, mice compared with the diabetic WT mice. Conclusion: The deletion of RasGRF1 attenuated myocardial fibrosis and improved cardiac function in diabetic mice through inhibiting inflammation and oxidative stress.

Although established guidelines currently recommend the use of the CHA2DS2-VASc score for evaluating embolic risk in AF patients, few studies have evaluated the use of the CHA2DS2-VASc score for predicting cardiovascular outcomes in patients with acute myocardial infarction (AMI). The aim of this study was to determine whether CHA2DS2-VASc score is a predictor of a major adverse cardiocerebral vascular event (MACCE) in AMI patients. This study analyzed data in the Taiwan National Health Insurance Research Database from January 2008 to December 2012. Cardiovascular outcomes were analyzed according to the baseline characteristics, presence of AF, and CHA2DS2-VASc score. Twenty nine thousand four hundred fifty-two patients with non-fatal AMI, 1171 patients (8.3%) were with AF. The Cox regress model showed with the exception of women sex and peripheral artery disease, all the baseline characteristics considered risks in CHA2DS2-VASc scores were independently associated with the increased incidence of MACCE within 1 year after AMI. A CHA2DS2-VASc score of

Interleukin (IL)-33, a member of the IL-1 family of cytokines, is involved in innate and adaptive immune responses via interaction with its receptor, ST2. Activation of ST2 signalling by IL-33 triggers pleiotropic immune functions in multiple ST2-expressing immune cells, including macrophages, neutrophils, eosinophils, basophils, mast cells, type 2 helper T cells, regulatory T cells, and group 2 innate lymphoid cells. IL-33-mediated effector functions contribute to the tissue inflammatory and reparative responses in various organs including lung, skin, kidney, central nerve system, cardiovascular system, and gastrointestinal system. Endogenous IL-33/ ST2 signaling exhibits diverse immune regulatory functions during progression of different diseases. IL-33 likely functions as a disease sensitizer and plays pathological roles in inflamed tissues in allergic disorders that involve hyperreactive immune responses in the context of skin and pulmonary allergy. However, IL-33 also mediates tissue-protective functions during the recovery phase following tissue injury in the central nerve system and gastrointestinal system. Modulation of the IL-33/ST2 axis, therefore, represents a promising strategy for treating immune disorders that involve dysregulation of the cytokine signalling. In the past two decades, therapeutic strategies blocking IL-33/ST2 have been extensively studied for the treatment of diseases in animal models. In this review, the current progress on the development of therapeutic biologics for targeting IL-33/ST2 signalling in inflammatory diseases is summarized.

Aims To evaluate the efficacy of bundled skin antiseptic preparation to prevent cardiac implantable electronic device (CIED) infections. Methods and results From January 2010 to November 2013, 665 consecutive patients were divided into two groups according to the strategy of skin preparation. In Period 1 (January 2010 to June 2012), 395 patients received the standard skin antiseptic preparation. In Period 2 (July 2012 to November 2013), 270 patients received a triple-step skin antiseptic preparation, ‘bundled skin antiseptic preparation’, consisting of applying 75% alcohol over anterior chest on the night before the index day, povidone-iodine 10 min before operation, and the standard skin antiseptic preparation before incision. During follow-up, the occurrence of CIED infection was recorded. Multiple logistic regression analysis was used to determinate the risk factors of CIED infection. During a mean follow-up of 26.9 ± 16.2 months, 20 episodes of CIED infection developed in 19 patients (2.9%), and the incidence of minor and major infection episodes was 2.2% and 0.8%, respectively. Patients with the bundled skin antiseptic preparation had a significantly lower incidence of CIED infection, compared with patients with the standard preparation (0.7 vs. 4.3%, P = 0.007). In multivariate analysis, pocket haematoma ( P = 0.020), atrial fibrillation ( P = 0.033), and complex procedures ( P = 0.047) were independent predictors for CIED infection. In contrast, the bundled skin antiseptic preparation was a significant predictor against CIED infection ( P = 0.014). Conclusion Pocket haematoma was the most important risk factor for CIED infection. The bundled skin antiseptic preparation strategy significantly reduced the risk of minor CIED infection.

Despite high in-hospital mortality associated with acute respiratory distress syndrome (ARDS), there is no effective therapeutic strategy. We tested the hypothesis that combined melatonin-mitochondria treatment ameliorates 100% oxygen-induced ARDS in rats. Adult male Sprague-Dawley rats (n = 40) were equally categorized into normal controls, ARDS, ARDS-melatonin, ARDS with intravenous liver-derived mitochondria (1500 μg per rat 6 hr after ARDS induction), and ARDS receiving combined melatonin-mitochondria. The results showed that 22 hr after ARDS induction, oxygen saturation (saO2 ) was lowest in the ARDS group and highest in normal controls, significantly lower in ARDS-melatonin and ARDS-mitochondria than in combined melatonin-mitochondria group, and significantly lower in ARDS-mitochondria than in ARDS-melatonin group. Conversely, right ventricular systolic blood pressure and lung weight showed an opposite pattern compared with saO2 among all groups (all P < 0.001). Histological integrity of alveolar sacs showed a pattern identical to saO2 , whereas lung crowding score exhibited an opposite pattern (all P < 0.001). Albumin level and inflammatory cells (MPO+, CD40+, CD11b/c+) from bronchoalveolar lavage fluid showed a pattern opposite to saO2 (all P < 0.001). Protein expression of indices of inflammation (MMP-9, TNF-α, NF-κB), oxidative stress (oxidized protein, NO-1, NOX-2, NOX-4), apoptosis (mitochondrial Bax, cleaved caspase-3, and PARP), fibrosis (Smad3, TGF-β), mitochondrial damage (cytochrome C), and DNA damage (γ-H2AX+) exhibited an opposite pattern compared to saO2 in all groups, whereas protein (HO-1, NQO-1, GR, GPx) and cellular (HO-1+) expressions of antioxidants exhibited a progressively increased pattern from normal controls to ARDS combined melatonin-mitochondria group (all P < 0.001). In conclusion, combined melatonin-mitochondrial was superior to either treatment alone in attenuating ARDS in this rat model.

Aim: Sitagliptin, an oral glucose-lowering agent, has been found to produce cardiovascular protection possibly via anti-inflammatory and anti-atherosclerotic activities of glucagon-like peptide-1 receptor (GLP-1). The aim of this study was to investigate whether sitagliptin protected the kidney function from acute ischemia-reperfusion (IR) injury in rats. Methods: Adult male SD rats were categorized into 4 groups: sham control, IR injury, IR+sitagliptin (300 mg/kg) and IR+sitagliptin (600 mg/kg). Acute renal IR injury of both kidneys was induced by clamping the renal pedicles for 1 h. The drug was orally administered at 1, 24 and 48 h after acute IR. Blood samples and 24-h urine were collected before and at 72 h after acute IR. Then the rats were sacrificed, and the kidneys were harvested for biochemical and immunohistochemical studies. Results: Acute IR procedure markedly increased serum levels of creatinine and BUN and the ratio of urine protein to creatinine. The kidney injury score, inflammatory biomarkers (MMP-9, TNF-α and NF-κB) levels and CD68+ cells in IR kidneys were considerably increased. The expression of oxidized protein, reactive oxygen species (NOX-1, NOX-2) and apoptosis proteins (Bax, caspase-3, PARP) in IR kidneys was also significantly upregulated. All these pathological changes were suppressed by sitagliptin in a dose-dependent manner. Furthermore, the serum GLP-1 level, and the expression of GLP-1 receptor, anti-oxidant biomarkers (HO-1 and NQO-1 cells, as well as SOD-1, NQO-1 and HO-1 proteins), and angiogenesis markers (SDF-1α+ and CXCR4+ cells) in IR kidneys were significantly increased, and further upregulated by sitagliptin. Conclusion: Sitagliptin dose-dependently protects rat kidneys from acute IR injury via upregulation of serum GLP-1 and GLP-1 receptor expression in kidneys.

// Tzu-Hsien Tsai 1, 2 , Cheng-Jei Lin 1, * , Sarah Chua 1 , Sheng-Ying Chung 1 , Cheng-Hsu Yang 1 , Meng-Shen Tong 1 and Chi-Ling Hang 1 1 Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 2 Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan * Indicates equal contribution in this study compared with the first author Correspondence to: Chi-Ling Hang, email: samuelhang@hotmail.com Keywords: brain damage, chronic cerebral hypoperfusion, melatonin Received: January 30, 2017 Accepted: June 19, 2017 Published: August 22, 2017 ABSTRACT Background: Vascular cognitive impairment (VCI) is a spectrum of cognitive impairment caused by various chronic diseases including aging, hypertension, and diabetes mellitus. Oxidative and inflammatory reactions induced by chronic cerebral hypoperfusion (CHP) are believed to cause VCI. Melatonin is reported to possess anti-oxidation and anti-inflammation effects. This study was designed to investigate the effect and mechanisms of melatonin in CHP mice model. Results: The behavioral function results revealed that CHP mice were significantly impaired when compared with the control. Melatonin improved the cognitive function, but the addition of MT2 receptor antagonist reversed the improvement. The IHC staining showed melatonin significantly improved WM lesions and gliosis in CHP mice. Again, the addition of MT2 receptor antagonist to melatonin worsened the WM lesion and gliosis. Similar results were also found for mRNA and protein expressions of oxidative reaction and inflammatory cytokines. Materials and Method: Forty C57BL/6 mice were divided into four groups: Group 1: sham control; Group 2: CHP mice; Group 3: CHP with melatonin treatment; Group 4: CHP-melatonin and MT2 receptor antagonist (all groups n = 10). Working memory was assessed with Y–arm test at day-28 post-BCAS (bilateral carotid artery stenosis). All mice were sacrificed at day-30 post-BCAS. The immunohistochemical (IHC) staining was used for white matter (WM) damage and gliosis. The expression of mRNA and proteins about inflammatory and oxidative reaction were measured and compared between groups. Conclusions: Partially through MT2 receptor, melatonin is effective for CHP-induced brain damage.

We tested the hypothesis that, as compared with conventional door-to-balloon, shortened door-to-balloon time would further improve 30-day outcome in ST-elevation myocardial infarction patients undergoing primary stenting.Retrospective cohort studyAcademic tertiary care hospital with approximately 2600 bedsBetween January 2008 and December 2009, 266 ST-elevation myocardial infarction patients underwent primary stenting with conventional Door-to-baloon were consecutively enrolled as group 1, while 293 ST-elevation myocardial infarction patients underwent primary stenting with shortened door-to-balloon between January 2010 and December 2011 were consecutively enrolled as group 2.Shorten door-to-balloon time.The results showed that time from chest pain onset to door did not differ between two groups (p0.1), whereas door-to-balloon time was significantly reduced in group 2 compared with that in group 1 (p0.0001). The prevalences of successful reperfusion, acute and subacute stent thrombosis, 30-day death or combined endpoint (defined as congestive heart failure ≥ New York Heart Association functional class 3 or 30-d death), and left ventricular function did not differ between two groups (all p0.05), whereas the peak creatine phosphokinase level was significantly reduced in group 2 (0.05). Further analysis showed that shortening the chest pain-to-reperfusion time to less than 240 minutes was the most important factor in improving left ventricular function (p0.001) and 30-day combined endpoint. Multivariate analysis showed that congestive heart failure greater than or equal to New York Heart Association functional class 3, poor left ventricular function, and age (all p0.001) along with unsuccessful reperfusion (p = 0.25) were independently predictive of 30-day mortality.Shortening the duration between chest pain onset and reperfusion to less than 4.0 hours was critical in reducing myocardial necrosis and improving heart function and 30-day mortality.