Sex-based outcomes after PCI in highbleeding risk patients: Results from the onyx one clear trial

BACKGROUND: While dual antiplatelet therapy (DAPT) constitutes the cornerstone of post-PCI pharmacotherapy, duration of DAPT in high bleeding risk (HBR) patients has not been fully defined especially with regard to sex. The results from the Onyx ONE Clear trial demonstrated favorable safety and efficacy after PCI with 1-month dual antiplatelet therapy (DAPT) in HBR patients treated with Resolute Onyx drug-eluting stents (DES). We sought to evaluate impact of sex on clinical outcomes in this trial. METHODS: In this prespecified subgroup analysis from Onyx ONE Clear, patients were divided into 2 groups according to sex. Primary endpoint was cardiac death or myocardial infarction (MI) from 1 month to 1 year. RESULTS: A total of 487 female patients (32%) and 1019 males (68%) were free from major ischemic events 1-month after PCI and were transitioned to single antiplatelet therapy.Women were older (p<0.001), had more HBR criteria (p=0.02), and higher rates of moderate/severe calcific lesions (p=0.03) compared to men. Men had higher rates of previous MI (p=0.003), atrial fibrillation (p=0.001), and multivessel coronary artery disease (p<0.001). Clinical outcomes between 1 and 12 months are shown in (Figure) and were similar for males and females except for target vessel revascularization which was greater for males (p=0.04). CONCLUSIONS: In HBR patients treated with Resolute Onyx DES and an abbreviated DAPT course of one month, rates of the primary endpoint of cardiac death or MI between 1 and 12 months were low and did not show any sex-based differences. These data support the use of an abbreviated DAPT regimen in men and women with HBR after PCI with Resolute Onyx DES.

Exact vortex nucleation and cooperative vortex tunneling in dilute Bose-Einstein condensates.

With the imminent advent of mesoscopic rotating Bose-Einstein condensates in the lowest Landau level regime, we explore lowest Landau level vortex nucleation. An exact many-body analysis is presented in a weakly elliptical trap for up to 400 particles. Striking non-mean-field features are exposed at filling factors >>1. For example, near the critical rotation frequency pairs of energy levels approach each other with exponential accuracy. A physical interpretation is provided by requantizing a mean-field theory, where 1/N plays the role of Planck's constant, revealing two vortices cooperatively tunneling between classically degenerate energy minima. The tunnel splitting variation is described in terms of frequency, particle number, and ellipticity.

Specific detection of chikungunya virus using a RT-PCR/nested PCR combination.

Chikungunya (CHIK) virus is enzootic in many countries in Asia and throughout tropical Africa. In Asia the virus is transmitted from primates to humans almost exclusively by Aedes aegypti, while various aedine mosquito species are responsible for human infections in Africa. The clinical picture is characterized by a sudden onset of fever, rash and severe pain in the joints which may persist in a small proportion of cases. Although not listed as a haemorrhagic fever virus, illness caused by CHIK virus can be confused with diseases such as dengue or yellow fever, based on the similarity of the symptoms. Thus, laboratory confirmation of suspected cases is required to launch control measures during an epidemic. CHIK virus diagnosis based on virus isolation is very sensitive, yet requires at least a week in conjunction with virus identification using monovalent sera. We developed a reverse transcription-polymerase chain reaction (RT-PCR) assay which amplifies a 427-bp fragment of the E2 gene. Specificity was confirmed by testing representative strains of all known alphavirus species. To verify further the viral origin of the amplicon and to enhance sensitivity, a nested PCR was performed subsequently. This RT-PCR/nested PCR combination was able to amplify a CHIK virus-specific 172-bp amplicon from a sample containing as few as 10 genome equivalents. This assay was successfully applied to four CHIK virus isolates from Asia and Africa as well as to a vaccine strain developed by USAMRIID. Our method can be completed in less than two working days and may serve as a sensitive alternative in CHIK virus diagnosis.

Evaluation of urine and serum metabolites in miniature schnauzers with calcium oxalate urolithiasis.

To evaluate underlying causes of calcium oxalate urolithiasis, 24-hour excretion of urine metabolites was measured in 6 Miniature Schnauzers that formed calcium oxalate (CaOx) uroliths during periods when they were fed a standard diet and during periods when food was withheld. Serum concentrations of parathyroid hormone and 1,25-dihydroxyvitamin D also were evaluated. Serum calcium concentrations were normal in all 6 affected Miniature Schnauzers; however, during diet consumption, mean 24-hour urinary excretion of calcium was significantly (P = 0.025) higher than calcium excretion when food was withheld. In 1 dog, urinary calcium excretion was lower during the period of food consumption, compared with the period when food was withheld. Compared with clinically normal Beagles, Miniature Schnauzers that formed CaOx uroliths excreted significantly greater quantities of calcium when food was consumed (P = 0.0004) and when food was withheld (P = 0.001). Miniature Schnauzers that formed CaOx uroliths excreted significantly less oxalate than clinically normal Beagles during fed (P = 0.028) and nonfed (P = 0.004) conditions. Affected Miniature Schnauzers also excreted abnormally high quantities of uric acid. Excretion of citrate was not different between Miniature Schnauzers with CaOx urolithiasis and clinically normal Beagles. In 5 of 6 Miniature Schnauzers with CaOx urolithiasis, concentrations of serum parathyroid hormone were similar to values from age- and gender-matched Miniature Schnauzers without uroliths. The concentration of serum parathyroid hormone in 1 dog was greater than 4 times the mean concentration of clinically normal Miniature Schnauzers. Mean serum concentrations of 1,25-dihydroxyvitamin D in Miniature Schnauzers with calcium oxalate urolithiasis were similar to concentrations of clinically normal Miniature Schnauzers.

Point mutations in the L-type pyruvate kinase gene of two children with hemolytic anemia caused by pyruvate kinase deficiency.

The molecular alterations responsible for the characteristic enzyme abnormalities in pyruvate kinase (PK) deficiency were investigated in two unrelated children homozygous for PK deficiency. Both variant enzymes were characterized according to the recommendations of the International Committee for Standardization in Haematology. Genomic DNA was specifically amplified by the polymerase chain reaction. Normal and mutant alleles of the L-type PK gene were analyzed by nucleotide sequencing. Heterozygosity of the parents was confirmed by allele-specific oligonucleotide hybridization. In PK Linz a C to T base exchange at position 394 of the L-type PK gene was found. As a result, the 132nd amino acid of the mutant enzyme, arginine (CGC), is replaced by cysteine (TGC). The affected amino acid residue is located within the deduced active site of the protein and the enzyme variant shows strongly altered allosteric properties. PK Beirut shows a C for T substitution at position 1058, changing the 353 amino acid from threonine (ACG) to methionine (ATG). In contrast to PK Linz, this amino acid lies outside the deduced substrate binding site and kinetic parameters of PK Beirut are close to normal. Both enzyme variants show a markedly reduced specific activity and thermolability.

Current problems in the evaluation of chemical safety.

Current problems in the safety evaluation of chemicals, including species differences in chemical toxicity, the difficulty in predicting whether metabolism will result in detoxication or activation, the different metabolic roles of tissue cytochromes P-450, and the significance of oxygen radical formation, are reviewed. A number of specific chemical problems are discussed, including the safety evaluation of benzene, methylene dichloride, DDT, dieldrin, TCDD, the PCBs, and the hepatotoxic drugs: benoxaprofen and tienilic acid. Two novel methods for the prospective evaluation of chemical toxicity are described, namely (i) computer optimized parametric analysis for chemical toxicity (COMPACT) based on the computer graphic determination of chemical structure and its relationship to specific cytochromes P-450 and hence toxicity, and (ii) enzyme activation in chemical toxicity (ENACT) based on the induction of specific cytochromes P-450 by the chemical, from which toxicity can be predicted.

[Biochemical changes in vinyl chloride poisoning. I. Effect of different conditions of vinyl chloride exposure on lipid metabolism in rats]. / Zmiany biochemiczne w zatruciach chlorku winylu. I. Wplyw róznych warunków ekspozycji na chlorek winylu na przemiane lipidowa u szczurów.

Lipids metabolism was evaluated in rats chronically exposed to vinyl chloride concentrations of 50, 500 and 20 000 ppm. The studies involved: 1) estimation of lipids content in serum; 2) estimation of cholesterol and triglycerides content in some tissues (liver, muscles, connective tissue, aortic wall), 3) evaluation of the rate of incorporating 14C-acetate into 14C-cholesterol in liver and the rate of its transition into blood. The studies were carried out after 1, 3, 6 and 10 months of vinyl chloride exposure. The results prove that under effects of vinyl chloride exposure some tendencies of an increase in the total and esterified cholesterol in serum vary with the magnitude of exposure (vinyl chloride airborne concentration, intoxication time). As to triglycerides and phospholipids at the final phase of intoxication (after 10 months) a significant increase in their serum content is found at the 20 000 ppm. concentration, whereas there are no changes in the free fatty acids level. As to the examined tissue only in liver some tendencies are found of a decrease in cholesterol content and much greater decrease in triglycerides level, which is progressing with intoxication time and exposure magnitude. No effect of vinyl chloride on the level of lipids in muscles, aortic wall and connective tissue were found. Studies of cholesterol synthesis in liver showed some increase in the rate of building 14C-acetate into cholesterol only in two highest vinyl chloride concentrations (500 and 20 000 ppm) after 10 months of exposure. The results demonstrate that chronic vinyl chloride exposure only slightly affects lipid metabolism. The most significant changes occur only after 10 months of exposure at the concentration of 20 000 ppm. It is supposed that the disturbances in lipid metabolism have no important contribution to vinyl chloride poisonings pathology.

Influence of chronic carbon disulphide intoxication on the development of experimental atherosclerosis in rats.

Rats fed on atherogenic diets containing 2% cholesterol and 0.5% cholic acid with or without 0.15% thiouracil were exposed to carbon disulphide (CS2) vapours (1 mg/l of air), five hours a day, six days a week for 6-10 months. Serum and aorta lipid contents were determined, and the extent of atherosclerotic changes was investigated. The following effects of chronic exposure to CS2 were found: (1) slower gain in body weight when rats were fed on atherogenic diet; (2) greater increase in serum cholesterol content (after thiouracil supplemented diet); (3) moderate increase in total cholesterol content in the aorta wall with a significantly increased esterified cholesterol fraction but none in phospholipid level in this tissue; and (4) more advanced lipid infiltrates of coronary arteries and endocardium, the latter predominantly in the aortic valves. These results together with data from previous studies indicate that metabolism of arterial lipids participates in the process of artheroma formation after chronic exposure to CS2 vapours.

Seasat altimeter calibration: initial results.

Preliminary analysis of radar altimeter data indicates that the instrument has met its specifications for measuring spacecraft height above the ocean surface (+/- 10 centimeters) and significant wave height (+/- 0.5 meter). There is ample evidence that the radar altimeter, having undergone development through three earth orbit missions [Skylab, Geodynamics Experimental Ocean Satellite 3 (GEOS-3), and Seasat], has reached a level of precision that now makes possible its use for important quantitative oceanographic investigations and practical applications.