19 research outputs found
Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial
IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved
Relationships Between Simple Grain Quality Parameters for the Estimation of Sorghum and Maize Hardness in Commercial Hybrid Cultivars
Grain hardness affects sorghum and maize processing properties
especially for dry milling. A variety of simple grain quality parameters
were assessed on 17 sorghum and 35 white maize hybrid cultivars
grown in six and four locations, respectively, in South Africa. The purpose
was to determine tests that can be used to distinguish hardness in
commercial sorghum and maize. The grains were characterized by test
weight (TW), thousand kernel weight (TKW), decortication with the
tangential abrasive dehulling device (TADD), and kernel size. Maize
was also characterized for susceptibility to breakage, stress cracking,
and near-infrared transmittance (NIT) milling index. Principal component
analysis showed that, in nontannin and tannin sorghums, TADD
hardness and TW were closely correlated (P < 0.001). In maize, TADD
hardness was closely correlated (P < 0.001) with NIT milling index and
TW. Hence, TADD hardness and NIT milling index or TADD hardness
and TW would be suitable for maize hardness evaluation. A combination
of TADD hardness, TW, TKW, and kernel size >3.35 mm can be
used together to select sorghum grain for hardness. It thus appears that
TADD hardness is an excellent method of estimating both sorghum
and maize hardness that can be applied for routine batch analysis and
cultivar evaluation.The International Sorghum and Millet Collaborative Research Support Program (INTSORMIL).http://www.nonprofitjournals.org/journals/cereal_chemistry.ht
Combined Nivolumab and Ipilimumab in Octogenarian and Nonagenarian Melanoma Patients
International audienceData regarding elderly melanoma patients treated with anti-PD-1 or anti-CTLA-4 antibodies are in favor of tolerability outcomes that are similar to those of younger counterparts. However, there are very few studies focusing on elderly patients receiving nivolumab combined with ipilimumab (NIVO + IPI). Here, we ask what are the current prescribing patterns of NIVO + IPI in the very elderly population and analyze the tolerance profile. This French multicenter retrospective study was conducted on 60 melanoma patients aged 80 years and older treated with NIVO + IPI between January 2011 and June 2022. The mean age at first NIVO + IPI administration was 83.7 years (range: 79.3â93.3 years). Fifty-five patients (92%) were in good general condition and lived at home. Two dosing regimens were used: NIVO 1 mg/kg + IPI 3 mg/kg Q3W (NIVO1 + IPI3) in 27 patients (45%) and NIVO 3 mg/kg + IPI 1 mg/kg Q3W (NIVO3 + IPI1) in 33 patients (55%). NIVO + IPI was a first-line treatment in 39 patients (65%). The global prevalence of immune-related adverse events was 63% (38/60), with 27% (16/60) being of grade 3 or higher. Grade â„ 3 adverse events were less frequent in patients treated with NIVO3 + IPI1 compared with those treated with NIVO1 + IPI3 (12% versus 44%, p = 0.04). In conclusion, the prescribing patterns of NIVO + IPI in very elderly patients are heterogeneous in terms of the dosing regimen and line of treatment. The safety profile of NIVO + IPI is reassuring; whether or not the low-dose regimen NIVO3 + IPI1 should be preferred over NIVO1 + IPI3 in patients aged 80 years or older remains an open question
Phenolic acid content of sorghum and maize cultivars varying in hardness
The role of phenolic acids on sorghum and maize hardness was evaluated among eight cultivars of each of the cereals representing hard and soft classes. Bran and flour fractions were evaluated for monomeric and diferulic phenolic acids using high performance liquid chromatographic and mass spectrometric (LCâMS/MS) techniques. Bran samples of harder grains had more phenolic acids than those of soft types. Intra-class testing showed slight differences in cultivars within the hard and soft classes. The content of phenolic acids was a useful indicator of hardness distinguishing between hard and soft maize and sorghum cultivars. Correlation coefficients between monomeric acids of maize bran, mostly ferulic acid, and grain hardness were higher than those of sorghum. Maize bran ferulic acid content was strongly correlated with Tangential Abrasive Dehulling Device (TADD) hardness (r = - 0.776, p < 0.001). This study is the first to show that there is a relationship between bran phenolic acid content and sorghum and maize hardness.The Natural Science and Engineering Research Council of Canada (NSERC) Discovery Grant Program, Canada Foundation for Innovation (CFI) -New Opportunities Fund (CFI-NOF) and CFI-Leaders Opportunity Funds (CFI-LOF) .http://www.elsevier.com/locate/foodchemhb2016Food Scienc