Effects of Oral Supplementation With Nitrate-Rich Beetroot Juice in Patients With Pulmonary Arterial Hypertension-Results From BEET-PAH, an Exploratory Randomized, Double-Blind, Placebo-Controlled, Crossover Study.

BACKGROUND: The nitrate-nitrite-nitric oxide (NO) pathway may represent a potential therapeutic target in patients with pulmonary arterial hypertension (PAH). We explored the effects of dietary nitrate supplementation, with the use of nitrate-rich beetroot juice (BRJ), in patients with PAH. METHODS AND RESULTS: We prospectively studied 15 patients with PAH in an exploratory randomized, double-blind, placebo-controlled, crossover trial. The patients received nitrate-rich beetroot juice (∼16 mmol nitrate per day) and placebo in 2 treatment periods of 7 days each. The assessments included; exhaled NO and NO flow-independent parameters (alveolar NO and bronchial NO flux), plasma and salivary nitrate and nitrite, biomarkers and metabolites of the NO-system, N-terminal pro-B-type natriuretic peptide, echocardiography, ergospirometry, diffusing capacity of the lung for carbon monoxide, and the 6-minute walk test. Compared with placebo ingestion of BRJ resulted in increases in; fractional exhaled NO at all flow-rates, alveolar NO concentrations and bronchial NO flux, and plasma and salivary levels of nitrate and nitrite. Plasma ornithine levels decreased and indices of relative arginine availability increased after BRJ compared to placebo. A decrease in breathing frequency was observed during ergospirometry after BRJ. A tendency for an improvement in right ventricular function was observed after ingestion of BRJ. In addition a tendency for an increase in the peak power output to peak oxygen consumption ratio (W peak/VO2 peak) was observed, which became significant in patients reaching an increase of plasma nitrite >30% (responders). CONCLUSIONS: BRJ administered for 1 week increases pulmonary NO production and the relative arginine bioavailability in patients with PAH, compared with placebo. An increase in the W peak/VO2 peak ratio was observed after BRJ ingestion in plasma nitrite responders. These findings indicate that supplementation with inorganic nitrate increase NO synthase-independent NO production from the nitrate-nitrite-NO pathway.

Improved survival for patients with de novo metastatic prostate cancer in the last 20 years.

INTRODUCTION: During recent years, several new life-prolonging therapeutic options have been introduced for patients with metastatic prostate cancer (mPCa). The aim of the present study was to evaluate the changes in the survival of patients diagnosed with mPCa prior to and in the early period of the implementation of these new agents. PATIENTS AND METHODS: The study population consisted of 207 men diagnosed in 1997 and 316 men diagnosed in the period 2007-2013 with de novo mPCa and managed with initial endocrine therapy. Men were followed for overall survival and PCa-specific survival. RESULTS: At the time of diagnosis, men diagnosed in the period 2007-2013 had less co-morbidity, lower prostrate-specific antigen levels and lower clinical tumour categories than men diagnosed in 1997. A significantly higher proportion of men diagnosed in 1997 were managed with surgical castration (57% versus 9%). Only one patient diagnosed in 1997 received second-line therapy compared with 81 men (26%) diagnosed in the period 2007-2013. The median overall survival was significantly longer for men diagnosed between 2007 and 2013 compared with men diagnosed in 1997 (39.4 months versus 24.2 months, p < 0.0001). Likewise, the cumulative incidence of PCa-specific death was higher among men diagnosed in 1997 compared with men diagnosed between 2007 and 2013, with 5-year cumulative incidences of 72% and 47%, respectively (p < 0.0001). CONCLUSION: Survival in men diagnosed with metastatic PCa has improved significantly over time. The improved survival can in part be explained by lead-time bias, but also by the introduction of new life-prolonging treatments.