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Early hepatocellular carcinoma (HCC) diagnosis is challenging. Moreover, for patients with alpha-fetoprotein (AFP)-negative HCC, this challenge is augmented. MicroRNAs (miRs) profiles may serve as potential HCC molecular markers. We aimed to assess plasma homo sapiens—(hsa)-miR-21-5p, hsa-miR-155-5p, hsa-miR-192-5p, and hsa-miR-199a-5p—expression levels as a panel of biomarkers for HCC in chronic hepatitis C virus (CHCV) patients with liver cirrhosis (LC), especially AFP-negative HCC cases, as a step toward non-protein coding (nc) RNA precision medicine. Subjects and methods: 79 patients enrolled with CHCV infection with LC, subclassified into an LC group without HCC (n = 40) and LC with HCC (n = 39). Real-time quantitative PCR was used to measure plasma hsa-miR-21-5p, hsa-miR-155-5p, hsa-miR-192-5p, and hsa-miR-199a-5p. Results: Plasma hsa-miR-21-5p and hsa-miR-155-5p demonstrated significant upregulation, while hsa-miR-199a-5p demonstrated significant downregulation in the HCC group (n = 39) when compared to the LC group (n = 40). hsa-miR-21-5p expression was positively correlated with serum AFP, insulin, and insulin resistance (r = 0.5, p < 0.001, r = 0.334, p = 0.01, and r = 0.303, p = 0.02, respectively). According to the ROC curves, for differentiating HCC from LC, combining AFP with each of hsa-miR-21-5p, hsa-miR-155-5p, and miR199a-5p improved the diagnostic sensitivity to 87%, 82%, and 84%, respectively, vs. 69% for AFP alone, with acceptable specificities of 77.5%, 77.5%, and 80%, respectively, and AUC = 0.89, 0.85, and 0.90, respectively vs. 0.85 for AFP alone. hsa-miR-21-5p/hsa-miR-199a-5p and hsa-miR-155-5p/hsa-miR-199a-5p ratios discriminated HCC from LC at AUC = 0.76 and 0.71, respectively, with sensitivities = 94% and 92% and specificities = 48% and 53%, respectively. Upregulation of plasma hsa-miR-21-5p was considered as an independent risk factor for HCC development [OR = 1.198(1.063–1.329), p = 0.002]. Conclusions: Combining each of hsa-miR-21-5p, hsa-miR-155-5p, and hsa-miR-199a-5p with AFP made it possible to identify HCC development in the LC patients’ cohort with higher sensitivity than using AFP alone. hsa-miR-21-5p/hsa-miR-199a-5p and hsa-miR-155-5p/hsa-miR-199a-5p ratios are potential HCC molecular markers for AFP-negative HCC patients. hsa-miR-21-5p was linked, clinically and via in silico proof, to insulin metabolism, inflammation, dyslipidemia, and tumorigenesis in the HCC patients’ group as well as for an upregulated independent risk factor for the emergence of HCC from LC in the CHCV patients.

Purpose The authors aim to investigate the altered monocytes subsets distribution in liver cirrhosis (LC) and subsequent hepatocellular carcinoma (HCC) in association with the expression level of plasma Homo sapiens (has)-miR-21-5p and hsa-miR-155-5p. A step toward non-protein coding (nc) RNA precision medicine based on the immune perturbation manifested as altered monocytes distribution, on top of LC and HCC. Methods Seventy-nine patients diagnosed with chronic hepatitis C virus (CHCV) infection with LC were enrolled in the current study. Patients were sub-classified into LC group without HCC ( n  = 40), LC with HCC ( n  = 39), and 15 apparently healthy controls. Monocyte subsets frequencies were assessed by flow cytometry. Real-time quantitative PCR was used to measure plasma hsa-miR-21-5p and hsa-miR-155-5p expression. Results Hsa-miR-21-5p correlated with intermediate monocytes ( r  = 0.30, p  = 0.007), while hsa-miR-155-5p negatively correlated with non-classical monocytes ( r  = − 0.316, p  = 0.005). ROC curve analysis revealed that combining intermediate monocytes frequency and hsa-miR-21 yielded sensitivity = 79.5%, specificity = 75%, and AUC = 0.84. In comparison, AFP yielded a lower sensitivity = 69% and 100% specificity with AUC = 0.85. Logistic regression analysis proved that up-regulation of intermediate monocytes frequency and hsa-miR-21-5p were independent risk factors for LC progression to HCC, after adjustment for co-founders. Conclusion Monocyte subsets differentiation in HCC was linked to hsa-miR-21-5p and hsa-miR-155-5p. Combined up-regulation of intermediate monocytes frequency and hsa-miR-21-5p expression could be considered a sensitive indicator of LC progression to HCC. Circulating intermediate monocytes and hsa-miR-21-5p were independent risk factors for HCC evolution, clinically and in silico proved. Graphical abstract

Objective A cohort study was conducted with the support of the WHO, where a standardized WHO protocol was followed to assess vaccine effectiveness (VE) against symptomatic RT‒PCR confirmed SARS‒CoV-2 infection among hospital health workers (HWs) eligible for vaccination at Al-Azhar University hospitals. Methods A WHO-supported cohort study was conducted from July 2022 through September 2023 and included 1249 HWs who were randomly selected and followed up biweekly for one year. At enrollment, nasopharyngeal (NP) and blood samples were collected from each participant and evaluated to detect SARS-CoV-2 RNA via a real-time PCR assay (QIAGEN) and for the quantitative detection of SARS-CoV-2 binding antibodies via the Roche Elecsys Anti-SARS-CoV-2 S immunoassay (Roche Diagnostics, GmbH, Germany). During follow-up, NP samples were collected from anyone who developed symptoms consistent with the WHO definition of suspected cases of SARS-CoV-2 infection. Results At enrollment, SARS-CoV-2 RNA was detected in 119/1235 (9.6%) HWs and 89% of the participants with positive RNA were asymptomatic. COVID-19-binding antibodies were detected among 1245/1248 (99.8%) HWs, and 53.2% of them had titers > 2500 U/mL, regardless of vaccination status. During follow-up, 232 participants had COVID-19 symptoms, but only 108 provided NP samples, and 18 (16.7%) of them were positive for SARS-CoV-2 RNA. No hospitalization or mortality was recordedat enrollment or during the follow-up period. The cumulative incidence of COVID-19 infection was higher among HWs with incomplete vaccination compared to unvaccinated, fully vaccinated, or those who received booster doses ( P  = 0.025). There was no significant difference in VE among HWs who were fully vaccinated or had booster doses compared with unvaccinated HWs, with adjusted VE values of 68% (95% CI -28–92%) and 64% (95% CI -170–95%), respectively ( P  = 0.106 and 0.318 respectively). The adjusted VE increased to 89% (95% CI -33–99%) among HWs with hybrid immunity compared with those who were unvaccinated with a previous COVID-19 infection ( P  = 0.082). Conclusion This study indicates that VE against symptomatic lab-confirmed SARS-CoV-2 infection was quite high with over 60% protection and was higher among HWs with hybrid immunity (immunity due to a combination of previous infection and vaccination) compared to unvaccinated HWs with previous COVID-19 infection. The findings also highlight the importance of completing the primary vaccination series against COVID-19. This study reveals a high rate of asymptomatic COVID-19, a lower rate of confirmed cases, who showed marked decrease in hospitalization and fatality rates. Real-world VE studies are essential to address several unresolved issues, such as the appropriate number of booster doses and the longevity of protection.

Background: Spontaneous bacterial peritonitis (SBP) is associated with the highest mortality among end-stage cirrhotic liver disease patients. Neutrophil CD11b expression increases on the neutrophil surface within 5 min of exposure to bacteria. Paracentesis remains the only accepted method for accurate evaluation of patients, with many drawbacks; hence, a diagnostic noninvasive marker with a very high sensitivity and high diagnostic accuracy is very necessary. Aim of the study: to evaluate the neutrophil CD11b as a non-invasive biomarker for the diagnosis of SBP, comparing its sensitivity and specificity to other traditional methods. Patients and Methods: 200 patients who had liver cirrhosis with ascites were recruited to the Hepatology department inpatient wards of the National Liver Institute, Menoufia University. They were divided into Group I: 100 patients with SBP and Group II: 100 patients with non SBP ascites. All studied patients were subjected to full clinical examination, abdominal ultrasound, paracentesis, and laboratory investigations including ascetic fluid (AF) examinations. The CD11b expression and its mean fluorescence intensity (MFI) were assessed on peripheral blood neutrophils by flowcytometry. Results: There was a significant increase in the MFI of CD11b in the SBP group compared to the non SBP group. At cut off >20 for MFI of CD11b with a sensitivity of 100% and specificity of 100% can discriminate between SBP and non SBP cases followed by ascetic fluid TLC examination at a cut off 0.26 (×103) with a sensitivity of 92%, and specificity of 96%, then, AF neutrophil count at cut off 0.25 (×103) with a sensitivity of 80%, specificity of 100%, and AF culture examination with a sensitivity of 56% and specificity of 100%. Conclusion: The measurement of CD11b MFI on peripheral blood neutrophils is a useful non-invasive marker with high sensitivity and specificity to predict SBP compared with other methods. Further large-scale studies are needed to study the value of CD11b MFI level in the SBP follow-up therapy.