Our study demonstrated that EC-AIA has distinct tumor characteristics and a poorer survival outcome compared to EC-A. This suggests a benefit of recognition of this unique entity as an aggressive variant of endometrial cancer.
Tazobactam/piperacillin (TAZ/PIPC) is a useful antimicrobial agent with broad antibacterial activity. Hypokalemia is considered a rare side eŠect of TAZ/PIPC; however, it may occur more often than previously thought. In this study, hypokalemia frequency and risk factors were examined in 420 patients treated with TAZ/PIPC. Our results demonstrated that the hypokalemia incidence was 24.8% (grade 1 2: 18.3%, grade 3 4: 6.4%). In addition, multivariate analysis revealed that age [odds ratio 1.057, 95% conˆdence interval 1.024 1.090, cutoŠ value 80.5 years] is a risk factor. Although the``Daily dosage/creatinine clearance'' was not signiˆcant in multivariate analysis, univariate analysis indicated it be to be signiˆcant, with a cutoŠ value of 294.9 mg/mL/min. Furthermore, a``body mass index of 19.7 kg/m 2 or higher'',``serum potassium level before administration of 3.95 mEq/L or more'', and``no empirical treatment for administration purposes'' appeared to prevent the hypokalemia development. Overall, the hypokalemia incidence rate in TAZ/PIPC-administered patients was as high as 20%, with patients aged > 80.5 years considered a highrisk group. Thus, careful monitoring of potassium levels in patients treated with TAZ/PIPC, particularly those aged > 81 years, is warranted.
The effects of pyridoxalated hemoglobin polyoxyethylene conjugate (PHP) and other hemoglobin-related substances on arterial blood pressure (ABP) and heart rate (HR) were examined. Infusion of PHP and other hemoglobin-related substances elevated ABP and increased HR. The degree of the increase in ABP and HR did not differ among the groups. There were species' differences in responses to PHP. Pretreatment with various blockers did not abolish the elevation of ABP. The pretreatment of NG-monomethyl-L-arginine dose-dependently reduced the elevation of ABP but did not completely abolish it. PHP also elevated ABP in conscious rats. The magnitude of the ABP elevation was significantly smaller than in the anesthetized rats. Results indicate that inhibition of nitric oxide (NO) might be responsible in part for the elevation of ABP, and the degree of the elevation would be dependent on the degree of contribution of NO to the regulation of ABP.
Termed the “double-edged swords of innate immunity” by Kaplan and Radic, neutrophil extracellular traps (NETs) are vital contributors to innate defenses but also participate in the pathogeneses of manifold diseases including systemic lupus erythematosus, rheumatoid arthritis, thrombosis, and cancer. Despite their vast clinical impact, NETs have proven difficult to study in high quantity and isolation; indeed, over 1.9E9 neutrophils are required for full NET coverage of a 96-well plate. Our group has developed a novel NET-mimicking structure for adaptable and reproducible high-throughput analyses of NETs in vitro. Rooted in a base composition of DNA and histones interacted by slow diffusion across an aqueous two phase system, these structures exhibit the same 10–100 nm diameter fibers as their physiological counterparts and can incorporate additional NET-associated proteins and peptides. This platform therefore enables unprecedented high-throughput probes of the roles of individual NET components in health and disease. In a pilot study exploiting this opportunity, our group expanded upon the previously-reported protection of NETs from nuclease-mediated degradation by the peptide LL-37. The comparison between LL-37-containing structures and control structures without the peptide, a data point unavailable endogenously, revealed a 4.5-fold increase in structural half-life conferred by LL-37 after exposure to DNase I. Similar ongoing experiments are exploring the lupus-linked activation of plasmacytoid dendritic cells by NETs. In this way, the reported platform provides new investigative angles for NET studies while also conferring a reproducibility and statistical power unattainable with cell-based methods.
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