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The new resolution of the micro-ultrasound platform paired with the PRI-MUS protocol shows promise for real-time visualization of suspicious lesions and targeting of biopsies. The improved performance of the protocol in more significant disease is consistent with the focus of the field on decreasing insignificant diagnoses and detecting high risk disease early.

Abstract-Although the pathogenic mechanisms involved in predisposing individuals to hypertension are not well defined, evidence is accumulating that suggests a strong genetic transmission. Animal studies and some clinical investigations have revealed that aberrant NO production may be an important contributing factor. Indeed, a missense mutation in the endothelial NO gene caused by a Glu298Asp alteration has been strongly associated with essential hypertension, coronary artery spasm, and myocardial infarction. Recently, another point mutation caused by a T-7863 C transition in the 5Ј-flanking region of the endothelial NO synthase gene has been identified and, like the Glu298Asp mutation, is associated with coronary artery spasm. The present study was conducted to determine the effect of the T-7863 C point mutation on hypertension. We investigated the interaction between the endothelial NO synthase T-7863 C polymorphism and blood pressure in a large (nϭ705) clinically healthy population. Allele frequencies for the T and C alleles were 62% and 38%, translating into 39%, 46% and 15% of the population having the T/T, T/C, and C/C genotypes, respectively, for the T-7863 C point mutation. Subjects with the C/C genotype had significantly higher systolic blood pressures and were 2.16(95% confidence interval, 1.3 to 3.7) more likely to be hypertensive. Therefore, the Ϫ786 C/C genotype in NO synthase is a significant contributing factor for increasing the risk of essential hypertension. Key Words: nitric oxide Ⅲ hypertension, essential Ⅲ mutation Ⅲ blood pressure Ⅲ polymorphism Ⅲ nitric oxide synthase T he pathogenesis of hypertension is multifactorial and involves both genetic and environmental mechanisms. Accumulating evidence from clinical and animal studies suggests that an alteration in NO metabolism may be a contributing factor in the pathogenesis of hypertension. 1,2 The potent vasodilator properties of NO in the resistance arteries, coupled with the genetic basis of hypertension, suggests that mutations affecting the endothelial NO (eNOS) gene, and consequently impairing NO release, might contribute to increased vascular resistance and in turn an elevation in systemic blood pressure (BP). Recent investigations have demonstrated that mutations affecting the eNOS gene may lead to impaired NO release. The G-to-T conversion at nucleotide 894 in the eNOS gene, which introduces an aspartic acid in place of a glutamic acid residue (Glu298Asp), is associated with an increased risk for myocardial infarction, 3 hypertension, 4,5 and coronary artery spasm. 6 Another variant in the eNOS 5Ј-flanking region gene has been identified. The variant is a result of a thymidine being replaced by a cytosine at nucleotide Ϫ786 (T-7863 C). 7 Like the Glu298Asp mutation, one manifestation of the T-7863 C mutation is increased risk for the risk of coronary spasm. 7 In a Japanese population, subjects with the T-7863 C homozygous genotype were at 3 times the risk for coronary spasm compared with those with the C/T or the T/T genotypes. 7 The...

AbstactBackgroundMany men diagnosed with prostate cancer are active surveillance (AS) candidates. However, AS may be associated with increased risk of disease progression and metastasis due to delayed therapy. Genomic classifiers, e.g., Decipher, may allow better risk-stratify newly diagnosed prostate cancers for AS.MethodsDecipher was initially assessed in a prospective cohort of prostatectomies to explore the correlation with clinically meaningful biologic characteristics and then assessed in diagnostic biopsies from a retrospective multicenter cohort of 266 men with National Comprehensive Cancer Network (NCCN) very low/low and favorable-intermediate risk prostate cancer. Decipher and Cancer of the Prostate Risk Assessment (CAPRA) were compared as predictors of adverse pathology (AP) for which there is universal agreement that patients with long life-expectancy are not suitable candidates for AS (primary pattern 4 or 5, advanced local stage [pT3b or greater] or lymph node involvement).ResultsDecipher from prostatectomies was significantly associated with adverse pathologic features (p-values < 0.001). Decipher from the 266 diagnostic biopsies (64.7% NCCN-very-low/low and 35.3% favorable-intermediate) was an independent predictor of AP (odds ratio 1.29 per 10% increase, 95% confidence interval [CI] 1.03–1.61, p-value 0.025) when adjusting for CAPRA. CAPRA area under curve (AUC) was 0.57, (95% CI 0.47–0.68). Adding Decipher to CAPRA increased the AUC to 0.65 (95% CI 0.58–0.70). NPV, which determines the degree of confidence in the absence of AP for patients, was 91% (95% CI 87–94%) and 96% (95% CI 90–99%) for Decipher thresholds of 0.45 and 0.2, respectively. Using a threshold of 0.2, Decipher was a significant predictor of AP when adjusting for CAPRA (p-value 0.016).ConclusionDecipher can be applied to prostate biopsies from NCCN-very-low/low and favorable-intermediate risk patients to predict absence of adverse pathologic features. These patients are predicted to be good candidates for active surveillance.

Renal cell carcinoma (RCC) is a heterogeneous disease that is usually asymptomatic until late in the disease. There is an urgent need for RCC specific biomarkers that may be exploited clinically for diagnostic and prognostic purposes. Preoperative fasting urine and serum samples were collected from patients with clinical renal masses and assessed with 1H NMR and GCMS (gas chromatography-mass spectrometry) based metabolomics and multivariate statistical analysis. Alterations in levels of glycolytic and tricarboxylic acid (TCA) cycle intermediates were detected in RCC relative to benign masses. Orthogonal Partial Least Square Discriminant Analysis plots discriminated between benign vs. pT1 (R2 = 0.46, Q2 = 0.28; AUC = 0.83), benign vs. pT3 (R2 = 0.58, Q2 = 0.37; AUC = 0.87) for 1H NMR-analyzed serum and between benign vs. pT1 (R2 = 0.50, Q2 = 0.37; AUC = 0.83), benign vs. pT3 (R2 = 0.72, Q2 = 0.68, AUC = 0.98) for urine samples. Separation was observed between benign vs. pT3 (R2 = 0.63, Q2 = 0.48; AUC = 0.93), pT1 vs. pT3 (R2 = 0.70, Q2 = 0.54) for GCMS-analyzed serum and between benign vs. pT3 (R2Y = 0.87; Q2 = 0.70; AUC = 0.98) for urine samples. This pilot study suggests that urine and serum metabolomics may be useful in differentiating benign renal tumors from RCC and for staging RCC.

No association was found between homocysteine levels or anticardiolipin antibody and vascular access thrombosis in our patient population.

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