Calcium administration correlated with adverse outcomes in critically ill patients receiving PN. The data suggest that administration of parenteral calcium to critically ill patients may be harmful.
Apoptosis can be triggered in two different ways, through the intrinsic or the extrinsic pathway. The intrinsic pathway is mediated by the mitochondria via the release of cytochrome C while the extrinsic pathway is prompted by death receptor signals and bypasses the mitochondria. These two pathways are closely related to cell proliferation and survival signaling cascades, which thereby constitute possible targets for cancer therapy. In previous studies we introduced two plant derived isomeric flavonoids, flavone A and flavone B which induce apoptosis in highly tumorigenic cancer cells of the breast, colon, pancreas, and the prostate. Flavone A displayed potent cytotoxic activity against more differentiated carcinomas of the colon (CaCo-2) and the pancreas (Panc28), whereas flavone B cytotoxic action is observed on poorly differentiated carcinomas of the colon (HCT 116) and pancreas (MIA PaCa). Apoptosis is induced by flavone A in better differentiated colon cancer CaCo-2 and pancreatic cancer Panc 28 cells via the intrinsic pathway by the inhibition of the activated forms of extracellular signal-regulated kinase (ERK) and pS6, and subsequent loss of phosphorylation of Bcl-2 associated death promoter (BAD) protein, while apoptosis is triggered by flavone B in poorly differentiated colon cancer HCT 116 and MIA PaCa pancreatic cancer cells through the extrinsic pathway with the concomitant upregulation of the phosphorylated forms of ERK and c-JUN at serine 73. These changes in protein levels ultimately lead to activation of apoptosis, without the involvement of AKT.
Aim:The aim of the present study was to formulate nano lipid vesicles of lornoxicam targeting to the specific site (inflamed area), and investigating it's in vivo anti-inflammatory activity in animals (rats). Methods: Liposomes of lornoxicam were prepared by thin film hydration method. Lornoxicam was loaded in stealth liposomes, conventional liposomes and coated conventional liposomes. Stealth liposomes were prepared by incorporating PEGylated lipids MPEGDSPE. Conventional liposomes Original Research Articlewere formulated using phospholipids Lipoid SPC-3 and cholesterol. Conventional liposomes were later coated with the hydrophilic biocompatible polymer chitosan which produced cationic liposomes. All the formulations were optimized to get the best entrapment efficiency. Results: The average size of the unsonicated liposomes was found to be 844.4 nm, whereas the average particle size of sonicated liposomes was found to be 195.5 nm. Coating of lipid vesicles was confirmed by zeta potential values using a nano zeta sizer instrument which showed that the chitosan coated liposomes exhibited a positive zeta potential compared to the uncoated liposomes which had a negative zeta potential values. The PDI was found to be 0.4, indicated good dispersion of uniformly sized lipid vesicles. All coated conventional, uncoated conventional and PEGylated liposomal formulations followed Higuchi model drug release profile. Stability study showed higher drug content at refrigeration temperature when compared to the formulations stored at room temperature, after a period of 4 weeks. Chitosan coated liposomes were found to be more stable as the coating with chitosan prevents the oxidation of phospholipids. In vivo study was carried out in rats for their anti rheumatoid which showed that there was a significant reduction in edema volume in the rat group administered with the liposomal formulation. Conclusion: PEGylated liposomes were found to be more effective and stable than the uncoated conventional liposomes.
Background The number of hospitals offering transcatheter aortic valve replacement (TAVR) programs has increased exponentially in the United States over past several years. Multiple prior studies indicate relationship between hospital volume and clinical outcomes for various cardiac procedures. Purpose The association between the hospital procedural volume and clinical outcomes for TAVR is yet poorly understood. In this study, we aim to examine the in-hospital outcomes after TAVR stratified by hospital volume within a nationally representative, large database. Methods The National Readmission Database (NRD) 2016–2019 was used to identify hospitals with established TAVR programs (performing ≥20 TAVRs/year). Based on annualized procedural volume of transfemoral TAVR, hospitals were stratified into tertiles of low, medium, and high volume TAVR centers. Rates of adverse in-hospital events (death, cardiac arrest, stroke, vascular complications, and permanent pacemaker), 30-day mortality, and 30-day readmission rates were examined. Multivariate logistic regression analysis was performed to compare overall outcomes following TAVR in low-, medium-, and high-volume centers; adjusted for baseline characteristics and comorbidity burden. Results Of 71 million discharge records reviewed, a total of 232,581 patients underwent transfemoral TAVR between 2016–2019. Of all the TAVR cases, 77,183 (33.2%), 75,987 (32.7%), and 79,411 (34.1%) were performed at low-, medium-, and high-volume hospitals respectively. The median number of annual TAVR procedures was 91, 229, and 456 in low-, medium-, and high-volume centers respectively. Adjusted in-hospital mortality was significantly higher in low-volume (OR: 1.40, 95% CI: 1.21–1.62, p<0.01) and medium-volume (OR: 1.29, 95% CI: 1.11–1.50, p<0.01) hospitals compared with high-volume centers. Similarly, adjusted 30-day mortality (OR: 1.45, 95% CI: 1.27–1.66, p<0.01), 30-day readmission rates (OR: 1.11, 95% CI: 1.05–1.18, p<0.01), and in-hospital cardiac arrest (OR: 1.20, 95% CI: 1.08–1.33, p<0.01) were significantly higher for centers in the lowest-volume tertile compared with those in the highest-volume tertile. There were no significant differences in hospital length of stay (mean, 4.3±6.5 days), in-hospital stroke, acute kidney injury, vascular complications, need for permanent pacemaker, or mechanical circulatory support post-TAVR between the three groups. Conclusion In the United States, an inverse volume-mortality relationship was observed for transfemoral TAVR procedures from 2016 through 2019. Mortality and readmission rates at 30 days post-TAVR were significantly higher at low-volume hospitals compared with high-volume hospitals. Further research focusing at establishing protocols and standardized training programs may help mitigate the discrepancy in TAVR outcomes amongst hospitals with discrepant procedural volume. Funding Acknowledgement Type of funding sources: None.
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