Real-Life Experience in the Efficacy and Safety of COVID-19 Vaccination in Patients with Advanced Cirrhosis.

COVID-19 infections accelerate liver decompensation and serious liver-related co-morbidities. The aim is to evaluate the safety and impact of COVID vaccines on hepatic disease progression in patients with advanced liver disease and to identify parameters that predict the occurrence of complications. The study involved 70 patients with advanced liver disease who were vaccinated with different COVID vaccines from January 2021 to April 2022. They were evaluated clinically. The laboratory investigation included a complete blood count, liver and kidney function tests, calculation of CTP and MELD scores, plasma levels of ammonia, abdominal ultrasound, and upper GI endoscopy. Twenty patients had experienced complications 64 ± 12 days from the last dose of a vaccination. Twenty patients (28.6%) developed hepatic decompensation and hypothyroidism (n = 11, 15.7%), and five (7.14%) patients developed splanchnic thrombosis. There were no COVID-19 reinfections except for two patients who received Sinopharm and developed vaccine-associated enhanced disease (2.9%). Complications after COVID vaccinations were correlated with ALT (r = 0.279, p = 0.019), serum sodium (r = -0.30, p = 0.005), creatinine (r = 0.303, p = 0.011), liver volume (LV) (r = -0.640, p = 0.000), and MELD score (r = 0.439, p = 0.000). Multivariate logistic regression revealed that LV is the only independent predictor (p = 0.001). LV ≤ 682.3 has a sensitivity of 95.24% and a specificity of 85.71% in predicting complications with an AUC of 0.935, p < 0.001. In conclusion, the hepatic reserve and prognosis in liver cirrhosis should be evaluated prior to COVID vaccinations using the MELD score and liver volume as promising risk stratification criteria. In summary, the research proposes a novel triaging strategy that involves utilizing the MELD score and liver volume as risk stratification parameters of the hepatic reserve and prognosis of advanced liver cirrhosis prior to COVID immunization to determine who should not receive a COVID vaccination.

Dapagliflozin, Liraglutide, and Their Combination Attenuate Diabetes Mellitus-Associated Hepato-Renal Injury-Insight into Oxidative Injury/Inflammation/Apoptosis Modulation.

In this study, we aim to explore the beneficial therapeutic impacts of dapagliflozin (Dapa), a highly potent, reversible, and selective sodium-glucose cotransporter-2 inhibitor, and liraglutide (Lira), a glucagon-like peptide-1 (GLP-1) receptor agonist, as hypoglycaemic agents for the management of diabetes mellitus (DM), as well as their combination against DM-induced complications, including hepato-renal injury. Indeed, the progression of DM was found to be associated with significant hepatic and renal injury, as confirmed by the elevated biochemical indices of hepatic and renal functions, as well as histopathological examination. Dapa, Lira, and their combination effectively attenuated DM-induced hepatic and renal injury, as confirmed by the recovery of hepatic and renal functional biomarkers. The administration of both drugs significantly reduced the tissue contents of MDA and restored the contents of GSH and catalase activity. Moreover, NF-κB and TNF-α expression at the protein and gene levels was significantly reduced in the liver and the kidney. This was in parallel with the significant reduction in the caspase-3 content in the liver and the kidney, as well as suppressed cleaved caspase-3 expression in the hepatic and renal specimens, as confirmed by immune-histochemical analysis. Notably, the combined Dapa/Lira treatment demonstrated an additive superior hepato-renal protective impact compared with the use of either drug alone. Thus, it appears that Dapa and Lira, through the coordinated modulation of oxidative, inflammatory, and apoptotic signalling, confer a significant hepato-renal protective impact against DM-induced complications and tissue injury.

Differential Effect of Three Macrolide Antibiotics on Cardiac Pathology and Electrophysiology in a Myocardial Infarction Rat Model: Influence on Sodium Nav1.5 Channel Expression.

Macrolides were reported to have cardiotoxic effects presented mainly by electrocardiogram (ECG) changes with increased risk in cardiac patients. We aimed to determine the impact of three macrolides, azithromycin, clarithromycin and erythromycin, on cardiac electrophysiology, cardiac enzyme activities, histopathological changes, and sodium voltage-gated alpha subunit 5 (Nav1.5) channel expression. We used eight experimental groups of male albino rats: vehicle, azithromycin (100 mg/kg), clarithromycin (100 mg/kg), erythromycin (100 mg/kg), MI + vehicle, MI + azithromycin (100 mg/kg), MI + clarithromycin (100 mg/kg) and MI + erythromycin (100 mg/kg); each group received chronic oral doses of the vehicle/drugs for seven weeks. ECG abnormalities and elevated serum cardiac enzymes were observed particularly in rats with AMI compared to healthy rats. Microscopic examination revealed elevated pathology scores for rats treated with clarithromycin in both experiments following treatment with erythromycin in healthy rats. Although rats with MI did not show further elevations in fibrosis score on treatment with macrolides, they produced significant fibrosis in healthy rats. Downregulation of cardiac Nav1.5 transcript was observed following macrolides treatment in both groups (healthy rats and rats with MI). In conclusion, the current findings suggested the potential cardiotoxic effects of chronic doses of macrolide antibiotics in rats with MI as manifested by abnormal ECG changes and pathological findings in addition to downregulation of Nav1.5 channels. Furthermore, in the current dose ranges, azithromycin produced the least toxicity compared to clarithromycin and erythromycin.

Serum Soluble Fibrinogen-Like Protein 2 Represents a Novel Biomarker for Differentiation Between Acute and Chronic Egyptian Hepatitis B Virus-Infected Patients.

Hepatitis B virus (HBV) infection is considered as one of the most serious public health problems worldwide including Egypt. Soluble fibrinogen-like protein 2 (sFGL2) is a well-known immunomodulator that is produced by the T cells and has a strong inhibitory effect on the proliferation of T cells and maturation of dendritic cells (DC). In the current study, serum levels of sFGL2 were assessed utilizing enzyme-linked immunosorbent assay (ELISA) technique among 20 acute HBV-infected patients, 55 chronic HBV-infected patients and 15 healthy individuals. In addition, serum levels of soluble FAS ligand (sFASL), soluble FAS receptor (sFAS) as well as interferon-γ (IFN-γ) were assessed and correlated to the levels of sFGL2. According to our results, serum levels of sFGL2 were significantly higher in the acute HBV-infected patients than in the chronic HBV-infected patients and healthy individuals. On the other hand, the serum levels of sFASL, sFAS and IFN-γ were significantly higher in the chronic than in acute HBV-infected patients. Also, serum sFGL2 levels were negatively correlated with the serum levels of sFASL, sFAS, IFN-γ and albumin as well as hemoglobin concentration. Furthermore, serum sFGL2 levels were positively correlated with the activities of ALT and AST and total bilirubin levels in serum. Thus, the current work highlights the possibility of utilizing serum sFGL2 level as a novel biomarker for the differentiation between acute and chronic Egyptian HBV-infected patients.

Application of the Box-Behnken design for the production of soluble curcumin: Skimmed milk powder inclusion complex for improving the treatment of colorectal cancer.

The main objective of this study was to develop a soluble product of the practically insoluble curcumin (CMN) to treat colorectal cancer more effectively than with pure CMN. To improve the solubility of CMN, various hydrophilic carriers of skimmed milk powder (SMP), polyvinylpyrrolidone (PVP), and mannitol (MNT) were utilized to prepare solid dispersion (SD) binary complexes. The prepared complexes were characterized in terms of their aqueous solubility and in vitro drug release and analyzed by Fourier transform infrared spectrophotometry, powder X-ray diffractometry, scanning electron microscopy, dynamic light scattering, and the novel dyeing test. Based on this characterization, the best SD complex was optimized using the Box-Behnken design (RSM-BBD). These results showed that the solubility of CMN was greatly improved in combination with SMP. The SD of CMN with SMP produced significantly improved solubility (0.646 ± 0.024 mg/ml) and dissolution (54.94 ± 3.21% at 5 min). Further, solid-state characterization revealed that the complex exhibited intermolecular inclusion of the drug and carrier. Also, the complex did not undergo any chemical modification owing to its amorphous form, and the novel dye test showed better coloring impact, indicating the solubility of CMN. The in vitro cytotoxicity of the complex showed that 50% inhibition (IC50) of SW480 and Caco-2 cells was achieved at a considerably lower concentration than that of pure CMN. Flow cytometry analysis confirmed that the cell cycle arrest was at G2/M phase (43.26% and 65.14%), and DNA fragmentation analysis investigation confirmed that the complex induced more DNA damage during apoptosis.