Monocytes subsets altered distribution and dysregulated plasma hsa-miR-21-5p and hsa-miR-155-5p in HCV-linked liver cirrhosis progression to hepatocellular carcinoma.

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.

Diagnostic Significance of hsa-miR-21-5p, hsa-miR-192-5p, hsa-miR-155-5p, hsa-miR-199a-5p Panel and Ratios in Hepatocellular Carcinoma on Top of Liver Cirrhosis in HCV-Infected Patients.

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.

Diffusion-Weighted MRI as Non-Invasive Diagnostic Tool for Rectal Cancer Aggressiveness and Correlation with KI-67 Expression in Tumor Tissue.

BACKGROUND AND AIM: Apparent diffusion coefficient (ADC) was suggested as a prognostic marker in rectal carcinoma (RC). However, reported data are inconsistent. The present study aimed to assess the relation between ADC value and Ki-67 expression index and other pathological parameters in Egyptian RC patients. MATERIALS AND METHODS: The study included 39 patients with newly diagnosed RC (non-mucinous adenocarcinoma). All patients underwent magnetic resonance imaging (MRI) scan by 1.5T magnet. Mean ADC value was calculated. Pathological features were assessed and Ki- 67 immunohistochemical expression was applied as a proliferative index (PI) biomarker. RESULTS: It was shown that patients with T4 tumors had significantly lower ADC values when compared with patients with T2 and T3 (0.903 ± 0.24 versus 1.157 ± 0.31 and 0.971 ± 0.26 respectively, p<0.001). Also, patients with circumferential resection margin (CRM) involvement had significantly lower ADC values when compared with patients without (0.905 ± 0.24 versus 1.109 ± 0.30, p=0.036). Patients with T4 tumors expressed significantly higher ki-67 PI when compared with patients with T2 and T3 tumors (75.71 ± 5.14 versus 46.25 ± 5.18 and 75.71 ± 5.14 respectively, p<0.001). Pearson's correlation coefficient identified a significant inverse correlation between ADC values and ki-67 PI (r=-367, p=0.027). CONCLUSION: ADC values of RC may reflect tumor staging and Ki-67 is closely related to the ADC value confirm this result.

Utility of Lung Ultrasound in Decision-making to Prioritize Hospital Admission for COVID-19 Patients: A Developing Country Perspective.

BACKGROUND AND AIMS: In the midst of this pandemic, planning the prioritization of hospital admissions for patients affected with COVID-19 should be of prime concern, particularly in healthcare settings with limited resources. Thus, in this study, we aimed to develop a novel approach to triage COVID-19 patients and attempt to prioritize their hospital admission using Lung Ultrasonography (LUS). The efficacy of LUS in triaging suspected COVID-19 patients and assessing the severity of COVID-19 pneumonia was evaluated; the findings were then compared with those obtained by chest computed tomography (CT). METHODS: This multicenter, cross-sectional study comprised 243 COVID-19 patients who presented to the emergency department in 3 major university hospitals in Egypt. LUS was performed by an experienced emergency or chest physician, according to the local protocol of each hospital. Demographic, clinical, and laboratory data were then collected from each patient. Each patient was subjected to chest CT scans and LUS. RESULTS: The mean age of the 243 patients was 46.7 ± 10.4 years. Ground-glass opacity, subpleural consolidation, translobar consolidation, and crazy paving were reported in the chest CT scans of 54.3%, 15.2%, 11.1%, and 8.6% of the patients, respectively. B-line artifacts were observed in 81.1% of the patients (confluent pattern, 18.9%). The LUS findings completely coincided with the CT findings (Kappa agreement value, 0.77) in 197 patients (81.1%) and offered a diagnostic sensitivity of 74%, diagnostic specificity of 97.9%, positive predictive value of 90.2%, and negative predictive value of 93.6% for the COVID-19 patients. Following the addition of O2 saturation to the lung imaging findings, the ultrasound method was able to demonstrate 100% sensitivity and specificity in accurately differentiating between severe and non-severe lung diseases. CONCLUSION: LUS with oxygen saturation might prove to be effective in prioritizing the hospital admission of COVID-19 patients, particularly in healthcare settings with limited resources.

Janus Kinase-2 Mutation Associated Portal Vein Thrombosis Complicating Liver Cirrhosis and Hepatocellular Carcinoma.

BACKGROUND: Portal vein thrombosis (PVT) might be a catastrophic event complicating liver cirrhosis and hepatocellular carcinoma (HCC). AIM: role of JAK2 RS V617F mutation as a risk factor for PVT development in liver cirrhosis and HCC. METHODS: A case control study conducted on 100 PVT patients (76 HCC and 24 liver cirrhosis) additionally, 100 healthy individuals used as a control group. PVT was diagnosed incidentally by Doppler ultrasound during routine follow-up HCC screening. Prothrombin G20210A mutation, MTHFR mutation, Factor V Leiden mutation (VFL), antithrombin III (ATIII), protein C, S, and antiphospholipid antibodies, along with JAK2 RS V617F  mutation by real-time polymerase chain reaction all were analyzed. RESULTS: Patients with PVT were significantly older (p <0.001), thrombocytopenic (p <0.001), with high alkaline phosphatase (p <0.001). JAK2 RS V617F mutation was found in 28/100 (28%) in idiopathic PVT complicating liver cirrhosis and hepatocellular carcinoma. Cases with positive JAK2 rs V617F mutation were significantly accompanied by protein S deficiency (P 0.03), LA absence (p 0.06), and high frequency of ascites (P 0.03). While, the MTHFR heterozygous mutation (p0.001), ATIII (P 0.02), and VFL (P 0.01) were more frequent with negative JAK2 rs V617F mutation. The comparison between demographic data and thrombophilic parameters in PVT cases revealed that no significant differences were recorded except for male gender, Diabetes Mellitus, splenomegaly significantly increased among HCC cases (p <0.05). CONCLUSIONS: JAK2 rs V617F mutation must be considered in any case of PVT with liver cirrhosis and hepatocellular carcinoma without identified thrombophilic risk factors, with potential considerations of evolving myeloproliferative disorders. New diagnostic and therapeutic implications are still awaited.