Association of uric acid with mortality in patients with stable coronary artery disease

ObjectiveThe association between uric acid and cardiovascular disease is poorly studied. We undertook this study to assess whether uric acid level predicts clinical outcome in patients with stable coronary artery disease (CAD) treated with percutaneous coronary intervention (PCI).Materials/MethodsThis study included 8149 patients with stable CAD who underwent PCI. Uric acid was measured before angiography. The primary end point was 1-year mortality. Quartiles of quartiles of uric acid were: 1.49 to < 5.49 mg/dl (1st quartile; n=2032 patients), 5.49 to < 6.40 mg/dl (2nd quartile; n=1981 patients), 6.40 to < 7.50 mg/dl (3rd quartile; n=2093 patients) and 7.50 to 21.90 mg/dl (4th quartile; n=2043 patients).ResultsThere were 196 deaths during the 1-year follow-up. The numbers of deaths (Kaplan-Meier estimates) according to uric acid quartiles were: 35 deaths (1.8%) in the 1st quartile, 30 deaths (1.6%) in the 2nd quartile, 45 deaths (2.2%) in the 3rd quartile and 86 deaths (4.3%) in the 4th quartile (unadjusted hazard ratio [HR]=1.60, 95% confidence interval [CI] 1.38-1.86, P < 0.001 for each standard deviation [SD] increase in the logarithmic scale). After adjustment for traditional cardiovascular risk factors, renal function and inflammatory status, the association between uric acid and 1-year mortality remained significant (adjusted HR=1.26, 95% CI 1.07-1.48; P=0.005 for each standard deviation increase in the logarithmic scale). Uric acid improved predictivity of the multivariable model regarding mortality (P=0.040).ConclusionsElevated level of uric acid is an independent predictor of 1-year mortality in patients with stable CAD treated with PCI.     

A bi-functional hepatitis B virus core antigen (HBcAg) chimera activates HBcAg-specific T cells and preS1-specific antibodies

A major problem in chronic hepatitis B virus (HBV) infection is that treatment with specific antivirals is life-long since they rarely induce a sustained response. An attractive option is therefore to combine antiviral therapy with some type of immune stimulator, such as a therapeutic vaccine. Several lines of evidence suggest that a key target for the cellular immune response is the HBV core antigen (HBcAg). However, it may also be of advantage to simultaneously improve the neutralizing antibody response to the surface (S) region of HBV. We therefore generated chimeric HBcAg particles expressing preS1 residues 1-42 at the tip of the spike region. We could show that this chimeric HBcAg-preS1 protein primed both HBcAg-specific T cells and antibodies to preS1. This strongly suggests that this may be a viable approach to develop an effective bi-functional therapeutic vaccine as an add-on for the treatment of chronic HBV infections.     

Vascular function and the role of oxidative stress in heart failure, heart transplant, and beyond

Using flow-mediated vasodilation (FMD), reactive hyperemia, and an acute oral antioxidant cocktail (AOC; vitamins C and E and α-lipoic acid), this study aimed to provide greater insight into altered vascular function and the role of oxidative stress in chronic heart failure patients with reduced ejection fraction (HFrEF) and at several time points beyond heart transplantation (HTx). A total of 61 age-matched subjects (12 healthy controls, 14 New York Heart Association class II and III HFrEF, and 35 HTx recipients [<3 years post-HTx, 5-10 years post-HTx, and >14 years post-HTx]) ingested either placebo (PL) or an AOC before FMD and reactive hyperemia testing of the brachial artery. Vascular function, as measured by FMD, was not different among the controls (6.8±1.9%), recent <3-year post-HTx group (8.1±1.2%), and the 5- to 10-year post-HTx group (5.5±1.0%). However, PL FMD was lower in the HFrEF (4.5±0.7%) and in the >14-year post-HTx group (2.9±0.8%). The AOC increased plasma ascorbate levels in all of the groups but only increased FMD in the controls (PL, 6.8±1.9%; AOC, 9.2±1.0%) and >14-year post-HTx recipients (PL, 2.9±0.8%; AOC, 4.5±1.3%). There were no differences in reactive hyperemia in any of the groups with PL or AOC. This cross-sectional study reveals that, compared with controls, vascular function is blunted in HFrEF, is similar soon after HTx, but is decreased with greater time post-HTx with free radicals implicated in this progression.     

Gender differences in clinicopathological features and survival in surgically treated patients with renal cell carcinoma: an analysis of the multicenter CORONA database

Purpose

To investigate gender differences in clinicopathological features and to analyze the prognostic impact of gender in renal cell carcinoma (RCC) patients undergoing surgery.

Methods

A total of 6,234 patients (eleven centers; Europe and USA) treated by radical or partial nephrectomy were included in this retrospective study (median follow-up 59 months; IQR 30–106). Gender differences in clinicopathological parameters were assessed. Multivariable Cox regression models were applied to determine the influence of parameters on disease-specific survival (DSS) and overall survival (OS).

Results

A total of 3,751 patients of the study group were male patients (60.2 %), who were significantly younger at diagnosis and received more frequently NSS than women. Significantly, more often high-grade tumors and simultaneous metastasis were present in men. Whereas tumor size and pTN stages did not differ between genders, clear-cell and chromophobe RCC was diagnosed less frequently, but papillary RCC more often in men. Gender also independently influenced DSS (HR 0.75, p < 0.001) and OS (HR 0.80, p < 0.001) with a benefit for women. However, inclusion of gender in multivariable models did not significantly gain predictive accuracies (PA) for DSS (0.868–0.870, p = 0.628) and OS (0.775–0.777, p = 0.522). Furthermore, no significantly different DSS and OS rates were found in patients undergoing NSS.

Conclusions

This study demonstrates important gender differences in clinicopathological features and outcome of RCC patients with improved DSS and OS for women compared to men, even if solely patients with clear-cell RCC or M0-stage are taken into evaluation. However, inclusion of gender in multivariable models does not significantly gain PA of multivariable models.     

Perceptual analysis of speech and the activity in the lateral pharyngeal walls before and after velopharyngeal flap surgery

The purpose of this study was to investigate the effects of velopharyngeal flap surgery on speech and its relation with the activity in the lateral pharyngeal wall. Videofluoroscopic recordings made before and after operation were used in this retrospective study, which comprised 28 patients who had pharyngeal flap surgery between 5:5 and 14:3 (mean 8:6) years:months of age at the Sahlgrenska University Hospital, Göteborg, Sweden. Twenty-four patients had different types of clefts and four had velopharyngeal impairment (VPI) without a cleft palate. Eleven had additional malformations. Speech and activity in the lateral pharyngeal walls were rated perceptually preoperatively and postoperatively. The study confirmed that patients with VPI can be helped by a velopharyngeal flap operation. There seemed to be a relation with the activity in the lateral pharyngeal wall and speech. The later the postoperative assessment, the better the speech, but the age at operation did not affect the result. The impact of additional anomalies and syndromes should be investigated further.     

Lipopolysaccharides,but not Angiotensin ll,lnduces Direct Pro‐lnflammatory Effects in Cultured Mouse Arteries and Human Endothelial and Vascular Smooth Muscle Cells

Angiotensin II (Ang II) might induce pro‐inflammatory effects directly in the vascular wall independently of its haemodynamic effects. The aim of our study was to investigate the putative direct pro‐inflammatory and vasomotor effects of Ang II and compare to those of lipopolysaccharides (LPS) in mouse isolated mesenteric resistance‐sized arteries (MRA) supported by experiments in cultured human primary endothelial and vascular smooth muscle cells. Results showed that 24‐hr organ culture of mouse MRA with 10 nM Ang II had, unlike 100 ng/mL LPS, no effects on IL‐6 or MCP‐1 secretion, VCAM1 mRNA expression or endothelial function, while Ang II significantly decreased maximal vasomotor responses to phenylephrine. In support, 24‐hr organ culture of mouse MRA significantly suppressed Agtr1a mRNA and augmented Tlr4 mRNA along with attenuated vasomotor responses to Ang II. Moreover, contrary to LPS and TNF‐α, Ang II and [Sar1]‐Ang II had no concentration‐ or time‐dependent effects on IL‐6 and MCP‐1 secretion in human umbilical vein endothelial cells (HUVEC) and human aortic smooth muscle cells (HASMC). AGTR1 or AGTR2 mRNA expression was undetectable in HUVEC, whereas HASMC expressed only AGTR1 mRNA. In summary, contrary to previous studies and the observed effects of LPS, we could not demonstrate direct vascular pro‐inflammatory effects of Ang II ex vivo or in vitro. As indicated by our results, down‐regulation or desensitization of AT₁R during culture may explain our findings.