Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Detection and Quantification of Anti-Inflammatory Cytokine in Sera and Urine of Sudanese Patients Infected with Schistosoma haematobium

Abstract Cytokines have been in focus of scientific in for more than decade now. Analyzing their expression has enabled a better understanding of pathogenesis of various diseases. Moreover, they are now for beyond their stage when they were of interest for pathophysiological research. In the present study, we used an assay to anti-inflammatory cytokines. One hundred and thirty sera and urine from egg positive individuals and 42 samples of healthy individuals in Eldeum locality-an endemic area of S. haematobum and 28 healthy individuals from non-endemic area were tested. Concentration of IL5 and IL10 is reverse. IL5 is low in serum but high in urine before treatment and high in serum and low in urine after treatment. IL10 is high in serum, low in urine before treatment and low in serum, high in urine after treatment

Synthesis and characterization of ZnO–TiO2–chitosan–escin metallic nanocomposites: Evaluation of their antimicrobial and anticancer activities

This work intended to formulate bio-nanocomposites of zinc oxide (ZnO), titanium oxide (TiO2), chitosan, and escin, characterize their physical properties, and evaluate their antimicrobial and anticancer properties. X-ray diffractometers (XRD) and scanning and transmission electron microscopes were applied to characterize the morphology and ultrastructure of chemically synthesized bio-nanocomposites. To investigate the functional groups of bio-nanocomposites, we used Perkin–Elmer spectrometers for Fourier transform infrared (FTIR) analysis and photoluminescence (PL) spectroscopy for PL spectrum analysis. Antimicrobial activities against bacterial and fungal strains were tested with agar well diffusion. Bio-nanocomposites were tested for anticancer effects on a MOLT4 blood cancer cell line using morphological analysis, methyl thiazole tetrazolium assay, apoptosis by acridine orange/ethidium bromide, and mitochondrial membrane potential (ΔΨm). In XRD, FTIR, and PL, the active compounds of ZnO–TiO2, chitosan, and escin peaks were observed. Our bio-nanocomposites demonstrated antimicrobial activity against bacterial and fungal pathogens. The bio-nanocomposite was cytotoxic to MOLT4 cells at an IC50 concentration of 33.4 µg·mL−1. Bio-nanocomposites caused cytotoxicity, changes in cell morphology, and mitochondrial membrane potential degradation, all of which resulted in apoptotic cell death. MOLT4 cells were found to be responsive to bio-nanocomposites based on ZnO–TiO2–chitosan–escin

Synthesis, Characterization, and Antimicrobial and Antiproliferative Effects of CuO-TiO2-Chitosan-Escin Nanocomposites on Human Leukemic MOLT4 Cells

Nanocomposites comprised of CuO-TiO2-chitosan-escin, which has adjustable physicochemical properties, provide a solution for therapeutic selectivity in cancer treatment. By controlling the intrinsic signaling primarily through the mitochondrial signaling pathway, we desired nanocomposites with enhanced anticancer activity by containing CuO-TiO2-chitosan-escin. The metal oxides CuO and TiO2, the natural polymer chitosan, and a phytochemical compound escin were combined to form CuO-TiO2-chitosan-escin nanocomposites. The synthesized nanocomposites were confirmed and characterized using FTIR spectroscopy, TEM, and UV-Vis absorption spectroscopy. A human leukemia cell line (MOLT-4) was used to assess the efficacy and selectivity of nanocomposites. Based on a cytotoxicity study, CuO-TiO2-chitosan-escin nanocomposites had inhibition concentrations (IC50) of 13.68, 8.9, and 7.14 µg/mL against human T lymphoblast cells after 24, 48, and 72 h of incubation, respectively. Compared with untreated MOLT-4 cells, CuO-TiO2-chitosan-escin nanocomposite-treated cells significantly increased (p < 0.05) caspase-3, -8, and -9 and decreased the levels of antioxidant enzymes GR, SOD, and GSH. Furthermore, MDA for lipid peroxidase and ROS levels significantly increased (p < 0.05) in the treated cells than in the untreated cells. Remarkably, CuO-TiO2-chitosan-escin nanocomposite-mediated control of cell cycles were mainly achieved through the activation of caspase-3, -8, and -9

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19

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