Adequate sedation of the patient is required for diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP). The anesthetic propofol, with its shorter half-life, affording ...better control, offers an alternative to the benzodiazepine midazolam. The aim of this randomized, controlled, unblinded study was to compare prospectively the quality of sedation under propofol and midazolam in patients undergoing ERCP.
A total of 80 patients were randomized to sedation with propofol alone (n = 40) or midazolam alone (n = 40). Blood pressure, pulse, and oxygen saturation were measured. Midazolam was given by the endoscopist and titrated to the patients' response during ERCP, to a maximum dose of 15 mg per patient. In the propofol group an anesthetist was present to administer the propofol and to observe the patient. Standardized testing procedures (Steward score, Trieger test) were used to determine the length of postendoscopy recovery time. Efficacy of sedation was assessed by investigators and patients, using scoring systems.
Complete ERCP and adequate sedation was possible in 80% of patients (32 out of 40) with midazolam, and in 97.5% of patients (39 out of 40) with propofol (P<0.01). The average propofol induction dose was 1.24 mg/kg body weight, with maintenance requiring a mean dose of 9 mg/kg body weight per hour, or the equivalent of 354 mg in total. The average dose of midazolam administered was 0.12 mg/kg body weight; the total dose averaged 8 mg. Recovery time in the propofol patients was significantly shorter (P<0.01). The investigators (P<0.01) and the patients (P<0.05) both judged the quality of sedation to be better in the propofol group. There were no differences in blood pressure, pulse, or oxygen saturation between the two groups. One patient in the propofol group (79 years old) suffered a protracted apneic phase accompanied by hypotension that was managed by manual ventilation and drug therapy, and led to no complications.
Propofol proves to be an excellent sedative for ERCP and shows a shorter recovery time than midazolam. Because of the narrow therapeutic window, we recommend close patient monitoring.
Abstract Objectives This study describes the characteristics of a real-world Asian patient population treated with transcatheter aortic valve replacement (TAVR) and evaluates their clinical outcomes. ...Background No previously reported randomized or observational studies adequately assess the safety and efficacy of TAVR in an Asian population. Methods The Asian TAVR registry is an international multicenter study that enrolled patients with aortic stenosis who underwent TAVR in Asian countries. Results In total, 848 patients with mean STS score of 5.2 ± 3.8% were enrolled between March 2010 and September 2014 at 11 centers in 5 countries. The Edwards Sapien or Medtronic CoreValve was implanted in 64.7% and 35.3% of patients, respectively. The procedural success rate was 97.5%. The 30-day and 1-year mortality rates were 2.5% and 10.8%, respectively. There was no difference in 1-year mortality between devices (Sapien: 9.4%; CoreValve: 12.2%; log-rank p = 0.40). The rates of stroke, life-threatening bleeding, major vascular complications and acute kidney injury (stage 2 to 3) were 3.8%, 6.4%, 5.0% and 3.3%, respectively. Moderate or severe paravalvular leakage was significantly more common with the CoreValve than Sapien (14.4% vs. 7.3%; p = 0.001). According to the multivariate model, a higher STS score, lower body mass index, New York Heart Association functional class III–IV symptoms, diabetes mellitus, prior cerebrovascular accident, low mean gradient at baseline, and moderate or severe paravalvular leakage were significantly associated with reduced survival. Conclusions Despite anatomical features of concern, the clinical outcomes of TAVR in our Asian population were favorable in comparison with those of previously published trials and observational studies. (The Asian Transcatheter Aortic Valve Replacement Registry Asian TAVR; NCT02308150 )
Summary Fibronectin (FN), a large heterodimeric glycoprotein, can be found in soluble form in plasma or in insoluble form as an extracellular matrix protein. Cellular FN is produced by various types ...of benign and malignant epithelial and mesenchymal cells and is widely distributed in malignant tumors. We evaluated FN expression in cancer cells (epithelial FN; E-FN) and intratumor stroma (stromal FN, S-FN) of 1596 invasive breast cancer samples using immunohistochemistry on tissue microarrays. Correlations of FN expression with clinicopathologic factors and patient survival were investigated. Among 1512 informative cases, E-FN expression was observed in 355 (23.5%) cases, and S-FN expression showed no/weak staining in 362 (23.9%), moderate staining in 744 (49.2%), and strong staining in 406 (26.9%) cases. E-FN expression was correlated with advanced pT ( P < .001) and pN ( P < .001), histologic type ( P = .006), high histologic grade ( P < .001), lymphovascular invasion ( P < .001), hormone receptor negativity ( P < .001), and human epidermal growth factor receptor-2 (HER2) positivity ( P < .001). Strong S-FN expression showed an association with advanced pN ( P = .002), histologic type ( P < .001), high histologic grade ( P < .001), lymphovascular invasion ( P < .001), and HER2 positivity ( P < .001). Patients with E-FN expression showed worse overall survival ( P < .001) and disease-free survival ( P < .001) than did those with negative expression of FN. E-FN expression was an independent prognostic factor, especially in the hormone receptor–positive group. Expression of S-FN did not have a significant effect on patient survival. In conclusion, E-FN expression could be a promising prognostic marker in patients with invasive breast cancer.
Eu3+- and Sm3+-doped YVO4 phosphors were produced by microwave heating reaction. When the microwave heating method was used, the particle size was very small and the particles tended to agglomerate. ...However, as the main heating time increased, the particle size increased and the agglomeration decreased. In the photoluminescence analysis, the emission spectrum exhibited a weak band for 5D0- > 7F1 at 594.91 and 602.33nm and strong sharp peaks at about 616.77 and 620.08nm due to the 5D0- > 7F2 transition of Eu3+. Microwave synthesis can provide a product without long time sintering as well as good homogeneous distribution of activators.
ObjectivesFirefighters face exposures associated with adverse health outcomes including risk for multiple cancers. DNA methylation, one type of epigenetic regulation, provides a potential mechanism ...linking occupational hazards to adverse health outcomes. We hypothesised that DNA methylation profiles would change in firefighters after starting their service and that these patterns would be associated with occupational exposures (cumulative fire-hours and fire-runs).MethodsWe profiled DNA methylation with the Infinium MethylationEPIC in blood leucocytes at two time points in non-smoking new recruits: prior to live fire training and 20–37 months later. Linear mixed effects models adjusted for potential confounders were used to identify differentially methylated CpG sites over time using data from 50 individuals passing all quality control.ResultsWe report 680 CpG sites with altered methylation (q value <0.05) including 60 with at least a 5% methylation difference at follow-up. Genes with differentially methylated CpG sites were enriched in biological pathways related to cancers, neurological function, cell signalling and transcription regulation. Next, linear mixed effects models were used to determine associations between occupational exposures with methylation at the 680 loci. Of these, more CpG sites were associated with fire-runs (108 for all and 78 for structure-fires only, q<0.05) than with fire-hours (27 for all fires and 1 for structure fires). These associations were independent of time since most recent fire, suggesting an impact of cumulative exposures.ConclusionsOverall, this study provides evidence that DNA methylation may be altered by fireground exposures, and the impact of this change on disease development should be evaluated.
Abstract Objectives This study sought to evaluate the optimal percutaneous coronary intervention techniques using drug-eluting stents for bifurcation coronary lesions. Background The optimal ...bifurcation stenting technique needs to be evaluated. Methods The trial included 2 randomization studies separated by the presence of side branch (SB) stenosis for patients having non–left main bifurcation lesions. For 306 patients without SB stenosis, the routine final kissing balloon or leave-alone approaches were compared. Another randomization study compared the crush or single-stent approaches for 419 patients with SB stenosis. Results Between the routine final kissing balloon and leave-alone groups for nondiseased SB lesions, angiographic restenosis occurred in 17.9% versus 9.3% (p = 0.064), comprising 15.1% versus 3.7% for the main branch (p = 0.004) and 2.8% versus 5.6% for the SB (p = 0.50) from 214 patients (69.9%) receiving 8-month angiographic follow-up. Incidence of major adverse cardiac events including death, myocardial infarction, or target vessel revascularization over 1 year was 14.0% versus 11.6% between the routine final kissing balloon and leave-alone groups (p = 0.57). In another randomization study for diseased SB lesions, 28.2% in the single-stent group received SB stents. From 300 patients (71.6%) receiving angiographic follow-up, between the crush and single-stent groups, angiographic restenosis rate was 8.4% versus 11.0% (p = 0.44), comprising 5.2% versus 4.8% for the main branch (p = 0.90) and 3.9% versus 8.3% for the SB (p = 0.12). One-year major adverse cardiac events rate between the crush and single-stent groups was 17.9% versus 18.5% (p = 0.84). Conclusions Angiographic and clinical outcomes were excellent after percutaneous coronary intervention using drug-eluting stents with any stent technique for non–left main bifurcation lesions once the procedure was performed successfully.
Nanofluid is a kind of new engineering material consisting of nanometer-sized particles dispersed in base fluid. In this study, various nanoparticles, such as multi-walled carbon nanotube (MWCNT), ...fullerene, copper oxide, and silicon dioxide have been used to produce nanofluids for enhancing thermal conductivity and lubricity. As base fluids, DI water, ethylene glycol, and oil have been used. To investigate the thermo-physical properties of nanofluids, thermal conductivity has been measured. The experimental results of thermal conductivity of nanofluids are compared with the modeling results predicted by Jang and Choi model
14. The stability of nanofluid has been estimated with UV–vis spectrophotometer. Thermal conductivity of nanofluid has been increased with increasing volume fraction of nanoparticle except for water-based fullerene nanofluid which has lower thermal conductivity than that of base fluid due to its lower thermal conductivity, 0.4
W/mK. Stability of nanofluid has been influenced by the characteristics between base fluid and suspended nanoparticles.
Both arginase (ARG2) and human cytomegalovirus (HCMV) have been implicated in tumorigenesis. However, the role of ARG2 in the pathogenesis of glioblastoma (GBM) and the HCMV effects on ARG2 are ...unknown. We hypothesize that HCMV may contribute to tumorigenesis by increasing ARG2 expression.
ARG2 promotes tumorigenesis by increasing cellular proliferation, migration, invasion and vasculogenic mimicry in GBM cells, at least in part due to overexpression of MMP2/9. The nor-NOHA significantly reduced migration and tube formation of ARG2-overexpressing cells. HCMV immediate-early proteins (IE1/2) or its downstream pathways upregulated the expression of ARG2 in U-251 MG cells. Immunostaining of GBM tissue sections confirmed the overexpression of ARG2, consistent with data from subsets of Gene Expression Omnibus. Moreover, higher levels of ARG2 expression tended to be associated with poorer survival in GBM patient by analyzing data from TCGA.
The role of ARG2 in tumorigenesis was examined by proliferation-, migration-, invasion-, wound healing- and tube formation assays using an ARG2-overexpressing cell line and ARG inhibitor, N (omega)-hydroxy-nor-L-arginine (nor-NOHA) and siRNA against ARG2 coupled with functional assays measuring MMP2/9 activity, VEGF levels and nitric oxide synthase activity. Association between HCMV and ARG2 were examined in vitro with 3 different GBM cell lines, and ex vivo with immunostaining on GBM tissue sections. The viral mechanism mediating ARG2 induction was examined by siRNA approach. Correlation between ARG2 expression and patient survival was extrapolated from bioinformatics analysis on data from The Cancer Genome Atlas (TCGA).
ARG2 promotes tumorigenesis, and HCMV may contribute to GBM pathogenesis by upregulating ARG2.
Abstract Purpose The standard 60-mg dose of fimasartan, a newly developed selective angiotensin II receptor blocker, is effective and safe for use in patients with mild to moderate hypertension. This ...study aimed to compare the efficacy and safety of low-dose (30 mg) fimasartan and placebo or valsartan (80 mg) for 8 weeks in patients with mild to moderate hypertension. Methods In this randomized trial, 293 patients (219 men; mean age, 54.24 9.77 years) with mild to moderate hypertension were enrolled. After randomization to receive 30-mg fimasartan (n = 115), placebo (n = 117), or 80-mg valsartan (n = 61), the treatment dose was kept constant without dose escalation for 8 weeks. The primary end point was improvement in sitting diastolic blood pressure (SiDBP) from baseline to 8 weeks that was compared between treatments with low-dose fimasartan and placebo. The secondary end point was the overall efficacy and safety of low-dose fimasartan compared with that of placebo or valsartan. Findings At week 8, SiDBP changed by –9.93 (8.86) mm Hg in the fimasartan group and by –2.08 (9.47) mm Hg in the placebo group, which indicated significant antihypertensive efficacy ( P < 0.0001). Efficacy was shown at week 4 as measured by SiDBP (–9.96 7.73 vs –2.27 7.85 mm Hg; P < 0.0001) or sitting systolic blood pressure (SiSBP) (–16.18 14.44 vs –1.95 13.48 mmHg; P < 0.0001) and at week 8 as determined by SiSBP (–15.35 16.63 vs –2.30 14.91 mm Hg; P < 0.0001). The fimasartan group exhibited more potent antihypertensive efficacy than the valsartan group both at week 4 (SiDBP, –9.96 7.73 vs –6.53 9.58 mm Hg P = 0.0123; SiSBP, –16.18 14.4 vs –7.65 12.89 mm Hg P = 0.0002) and at week 8 (SiDBP, –9.93 8.86 vs –5.47 8.96 mm Hg P = 0.0021; SiSBP, –15.35 16.63 vs –7.49 13.68 mm Hg P = 0.0021). Most treatment-emergent adverse events (TEAEs) were mild (89 of 95), and there were no serious TEAEs. The incidence of TEAEs was 19.1% in the fimasartan group, 22.6% in the placebo group, and 13.6% in the valsartan group, with no significant differences. Implications Low-dose fimasartan (30 mg) was well tolerated during the study period with no significant TEAEs. Low-dose fimasartan had an effective blood pressure–lowering effect that was greater than that of 80-mg valsartan in patients with mild to moderate hypertension. ClinicalTrials.gov identifier: NCT01672476.