In chronic angina patients, ranolazine monotherapy was well tolerated and increased exercise performance throughout its dosing interval at all doses studied without clinically meaningful hemodynamic effects. One-year survival was not lower than expected in this high-risk patient population. This metabolic approach to treating myocardial ischemia may offer a new therapeutic option for chronic angina patients.

Background NUT midline carcinoma, renamed NUT carcinoma (NC), is an aggressive squamous cancer defined by rearrangement of the NUTM1 gene. Although a subset of patients can be cured, for the majority of patients the prognosis is grim. We sought to classify patients into risk groups based on molecular and clinicopathologic factors at the time of diagnosis. Methods Clinicopathologic variables and survival outcomes were extracted for a total of 141 NC patients from the NUT midline carcinoma Registry using questionnaires and medical records. Translocation type was identified by molecular analyses. Survival tree regression analysis was performed to determine risk factors associated with overall survival (OS). Results For 141 patients, the median age at diagnosis was 23.6 years. Fifty-one percent had thoracic origin compared with 49% nonthoracic sites (41% head and neck, 6% bone or soft tissue, 1% other). The median OS was 6.5 months (95% confidence interval [CI] = 5.8 to 9.1 months). Most patients had the BRD4-NUTM1 fusion (78%), followed by BRD3-NUTM1 (15%) and NSD3-NUTM1 (6%). Survival tree regression identified three statistically distinct risk groups among 124 patients classified by anatomical site and genetics: group A is nonthoracic primary, BRD3-, or NSD3-NUT (n = 12, median OS = 36.5 months, 95% CI = 12.5 to not reported months); group B is nonthoracic primary, BRD4-NUT (n = 45, median OS = 10 months, 95% CI = 7 to 14.6 months); and group C is thoracic primary (n = 67, median OS = 4.4 months, 95% CI = 3.5 to 5.6 months). Only groups A and B had long-term (≥3 years, n = 12) survivors. Conclusions We identify three risk groups defined by anatomic site and NUT fusion type. Nonthoracic primary with non-BRD4-NUT fusion confers the best prognosis, followed by nonthoracic primary with BRD4-NUT. Thoracic NC patients, regardless of the NUT fusion, have the worst survival.

Background— To explore potential interrelationships between lipoprotein-associated phosholipase A2 (Lp-PLA 2 ) , the metabolic syndrome (MetS), and incident cardiovascular disease (CVD). Methods and Results— MetS was defined by the National Cholesterol Education Program Adult treatment Panel III criteria in 4480 nondiabetic Malmö Diet and Cancer Study subjects without history of CVD. Incidence of first CVD event (stroke [130 cases] or myocardial infarction [131]) was monitored over 10 years of follow-up. Lp-PLA 2 activity and mass were significantly higher in subjects with MetS. Lp-PLA 2 activity compared with Lp-PLA 2 mass was more strongly correlated to individual components and increased more linearly with number of MetS components. Elevated Lp-PLA 2 activity (top compared with bottom tertile), but not elevated Lp-PLA 2 mass, increased risk for incident CVD (relative risk, RR: 1.54, 95% CI 1.07 to 2.24), as did MetS (1.42, 1.06 to 1.90) after taking possible confounders into account. Relative to those without either elevated Lp-PLA 2 activity or MetS, combination of MetS and elevated Lp-PLA 2 activity increased risk for CVD (1.97, 1.34 to 2.90). Elevated Lp-PLA 2 activity without MetS increased risk for CVD (1.40, 1.03 to 1.92) but not MetS without elevated Lp-PLA 2 activity (1.46, 0.94 to 2.27). Conclusion— Lp-PLA 2 is associated to the MetS. Higher plasma levels of Lp-PLA 2 increased risk for incident CVD regardless of MetS. The simultaneous presence of elevated Lp-PLA 2 activity and MetS may identify an especially high risk individual.

Lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) is an enzyme that is produced by inflammatory cells (macrophages, T-lymphocytes and mast cells) and hydrolyzes oxidized phospholipids in LDL. Several epidemiology studies indicate that Lp-PLA 2 appears to be an independent marker of cardiovascular risk. This study was conducted to define the distribution of Lp-PLA 2 in a large population-based cohort and to determine associations between Lp-PLA 2 and other risk factors for CVD. The study group consisted of participants from the Malmö Diet and Cancer study (1992)(1993)(1994). LpPLA 2 (activity and mass) was measured from samples obtained at baseline for 5,402 participants (3,167 women). A strong correlation was observed between LpPLA 2 activity and mass in this study (r=0.57). Highest correlations were observed between Lp-PLA 2 activity and LDL (r=0.45) and LDL/HDL ratio (r=0.54) and a strong inverse correlation to HDL (r=-0.31). The correlations between Lp-PLA 2 mass and lipids were not as strong as the correlation between activity and lipids.LpPLA 2 activity and mass were correlated with increased ultrasound determined carotid intima-media thickness. We conclude that LpPLA 2 is strongly correlated with several cardiovascular risk factors, especially lipid fractions, and with the degree of carotid artery atherosclerosis. However, the measured variables accounted for only 19% and 35% of the variation in Lp-PLA 2 mass and activity respectively. cardiovascular disease, epidemiology, Lp-PLA 2 , risk factor 3 INTRODUCTION