Relation of Liver Siderosis to Liver Fibrosis in Hemodialysis Patients With Severe Hyperferritinemia Secondary to High Doses of Intravenous Iron Supplementation.

OBJECTIVE: Aggressive iron substitution in hemodialysis (HD) patients leads to iron overload. The association between liver siderosis and fibrosis is still debatable. We studied the association of liver siderosis with liver fibrosis in HD patients. Furthermore, we studied the performance of liver stiffness measurements (LSMs) in identifying advanced liver fibrosis. We investigated the performance of biochemical indicators of iron status in identifying advanced liver fibrosis. METHODS: Fifty-five HD patients (average HD duration 6 ± 2 years) with hyperferritinemia secondary to intravenous iron supplementation (weakly iron dose 252.7 ± 63 mg; median blood transfusions 3 [2-5]) were recruited. The liver fibrosis grade was determined with Fibroscan, aminotransferase-to-platelet ratio index (APRI), and Fib-4 index. Liver iron concentration (LIC) was estimated with magnetic resonance imaging (MRI). Iron parameters and liver function biochemical indicators were also assessed. RESULTS: The median serum ferritin and transferrin saturation (TSAT) were 3531 µg/L and 77%, respectively. 34.5%, 20%, and 45.5% of the patients showed mild, moderate, or severe liver siderosis, respectively. All patients with severe liver siderosis showed advanced liver fibrosis. Patients with severe liver siderosis and advanced liver stiffness showed higher serum iron, TSAT, aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum bilirubin, APRI, and Fib-4 index scores than those with mild liver siderosis. Serum iron and TSAT showed good utility in identifying advanced liver fibrosis determined with Fibroscan, APRI, and Fib-4 index. Liver stiffness exhibited good utility in identifying advanced liver fibrosis diagnosed with APRI and Fib-4 index. CONCLUSIONS: High weekly intravenous iron dose associated with severe hyperferritinemia, high serum iron, and TSAT might lead to severe liver siderosis and concomitant liver fibrosis in HD patients. Serum iron, TSAT, Fibroscan, Fib-4, and APRI scores might offer noninvasive tools for identifying advanced liver fibrosis in those patients.

Antibodies against a mutated citrullinated vimentin in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by autoantibodies against citrullinated antigens. The anti-cyclic citrullinated peptide (Anti-CCP) test is commonly used to diagnose rheumatoid arthritis, whereas the anti-mutated citrullinated vimentin (Anti-MCV) is another anti-citrullinated antibody that reacts with mutated citrullinated vimentin. Therefore, we aimed to assess the diagnostic value of anti-MCV antibodies in RA patients and their relation to disease activity. This study included 60 RA patients and 25 normal controls. The disease activity of RA patients was assessed by disease activity score (DAS-28). ELISA was used to test patients and controls for anti-MCV and anti-CCP. The level of anti-MCV was significantly higher among patients with RA compared to the control group (1.56 ± 0.56 vs. 1.20 ± 0.19 mol/l; P< 0.001). Anti-MCV at cut-off point of > 1.2 mol/l had 76% sensitivity and 100% specificity, with an overall diagnostic accuracy of 83.2% for diagnosing RA. Regarding early RA diagnosis, anti-MCV at the cut-off point was > 1.2 mol/l with 70% sensitivity and 100% specificity. For diagnosis of late RA, the cut-off point was > 1.2 mol/l, with 93.3% sensitivity and 100% specificity, whereas the overall diagnostic accuracy was 96.3%. In this study, patients with positive anti-CCP had a marginally higher level of anti-MCV compared to those with negative anti-CCP (1.64 ± 0.28 vs. 1.48 ± 0.73 mol/l; P= 0.29). We concluded that serum levels of Anti-MCV can be used as a diagnostic test in RA. The increased serum levels of Anti-MCV, demonstrated the importance of Anti-MCV as an independent serum marker in predicting the outcome of RA.

Serum Galanin in Children with Autism Spectrum Disorder.

Recent studies have attempted to measure several biomarkers to understand the complex interactions of the anatomic systems that may be involved in autism spectrum disorder (ASD). In CNS, galanin takes part in a variety of pathological and physiological processes. Prior research has indicated it is involved in several neuropsychiatric disorders and has a role in inhibiting the neuronal firing and release of serotonin, norepinephrine, and acetylcholine. To date, serum galanin levels have not been investigated in the context of ASD. This study aimed, therefore, to compare the serum galanin levels of children with ASD and healthy controls and to reveal any association between galanin level and the severity of ASD, as well as other psychological and demographic parameters. Serum galanin levels were measured by radioimmunoassay in 116 children with ASD and 98 healthy children. We observed significantly increased serum concentrations of galanin in children with ASD relative to healthy children. Moreover, children with severe ASD had significantly higher galanin levels than those with less severe disease. We also confirmed significant positive correlations between galanin and psychiatric parameters in children with ASD. For the first time, we suggest a possible correlation between serum galanin and the degree of ASD severity. Increased galanin levels may play a role in the pathogenesis of ASD.

CXCR4 as a prognostic marker in Egyptian chronic lymphocytic leukemia patients.

Chronic lymphocytic leukemia (CLL) has variable clinical presentations, and molecular and biological prognostic markers. The C-X-C chemokine receptor 4 (CXCR4) and its ligand stromal cell-derived factor-1 (SDF-1) play an important role in trafficking of lymphocytes and monocytes. The aim was to study lymphocyte expression of CXCR4 and its prognostic value in CLL. A case control study was carried out on 30 newly diagnosed CLL cases and 30 healthy controls. Fludarabine, cyclophosphamide, and rituximab (FCR) was the standard treatment. Flowcytometric measurement of CXCR4 expression on lymphocytes was done. CXCR4 was significantly higher in patients than controls (81.67 ± 17.95 vs. 11.78 ± 2.78; P< 0.001). CXCR4 was significantly higher (P<0.001) in high risk CLL (93.63 ± 6.78) vs. intermediate risk (82.50 ± 7.13) and low risk (75.84 ± 12.23). CXCR4 was significantly higher (P<0.001) in non-responders (91.63 ± 6.98) vs. partial responders (83.11 ± 5.55) and complete responders (70.11 ± 4.44). CXCR4 was significantly lower in survivors vs. non-survivors (80.89 ± 5.09 vs. 85.43 ± 5.51; P< 0.001. CXCR4 had significant positive correlation with WBCs (r=0.45, P=0.01) and lymphocytes (r=0.40, P=0.01) measured at diagnosis. In conclusions, expression of CXCR4 in newly diagnosed CLL is significantly high. CXCR4 increased expression is associated with poor prognosis and resistance to the therapy.so it can be used as prognostic tool.

Diagnostic values of microRNA 27a in breast cancer patients.

Breast cancer is one of the most malignant tumors in women across the globe. Diagnosis of breast cancer at early stages is essential to improve treatment outcomes and decrease mortality rates. There is a pressing need for new non-invasive biomarkers to improve early diagnosis of breast cancer. This study aims to assess plasma miR-27a for the early diagnosis of breast cancer. miR-27a was evaluated in a total of 95 blood samples, 40 newly diagnosed cancer patients, 20 patients with benign breast lesions, 20 females with positive family history for breast cancer and 15 apparently healthy controls, using quantitative real time polymerase chain reaction. Our results exhibited significantly higher expression level of plasma miR-27a in breast cancer patients (median= 8.3 and 19 fold change for early and late stages respectively) compared to controls, high risk group and benign group with (P <0.001) for each. Plasma miR-27a was significantly higher in late breast cancer (median=19 fold change) compared to early breast cancer (median= 8.3) with (P <0.001). There was no statistically significant difference of plasmamiR-27a levels in benign group (median=1.8 fold change) compared to both control group and high risk group. There was no statistically significant difference of plasma miR-27a levels in high risk group (median= 1.2 fold change) compared to control group (median= 1 fold change). We performed Receiver Operating Characteristic (ROC) analysis for discriminating malignant from non-malignant cases. Plasma miR-27a yielded an area under the curve (AUC) of 0.983 with sensitivity 97.5%, specificity 91% and accuracy 94%.We concluded that miR-27a expression level represents sensitive and specific non-invasive molecular biomarkers for diagnosis of breast cancer.

Polymorphism of interleukin-1ß and interleukin-1 receptor antagonist genes in children with autism spectrum disorders.

In this study, we first investigated interleukin-1 beta (IL-1ß) and IL-1 receptor antagonist (IL-1RA) levels in a cohort of Egyptian children with autism spectrum disorder (ASD) and in healthy controls. Second, we examined the single-nucleotide polymorphisms (SNPs) at positions -31 and - 511 of the IL-1ß gene promoter and IL1RA and assessed the association between IL1B and IL1RA polymorphisms with ASD. We examined IL1ß promoter polymorphism at -511 (IL-1ß-511) and - 31 (IL-1ß-31) and IL1RA gene polymorphism in 80 children with ASD and 60 healthy children. The children with ASD had significantly higher levels of IL-1ß and IL-1RA than the controls. The children with ASD also had significantly higher frequencies of homozygous (CC) and heterozygous (TC) genotype variants of IL-1ß-511, and IL-1RA than the controls. Moreover, the frequency of the IL-1ß-511 allele (C) was higher in the ASD group than in the controls (p = .001). The homozygous and heterozygous variants of IL-1RA allele II were also significantly higher in the ASD group than in the control group. There was no significant association between the IL-1ß-31 genotype and autism classes. However, there were significant differences in the distribution of the IL-1RA heterogeneous genotype and allele II among children with severe autism. The inflammatory role of cytokines has been implicated in a variety of neuropsychiatric pathologies, including autism. Our data show alterations in the IL-1ß system, with abnormally increased serum levels of IL-1ß and IL-1RA in the children with ASD. Further, polymorphisms in the IL-1ß-511 and IL-1RA genotype variants correlated positively with autism severity and behavioral abnormalities. IL-1ß-511 and IL-1RA gene polymorphisms could impact ASD risk and may be used as potential biomarkers of ASD. Variations in the IL-1ß and IL-1RA systems may have a role in the pathophysiology of ASD.

Interleukin 18 as a new inflammatory mediator in left ventricular hypertrophy in children with end-stage renal disease.

Left ventricular hypertrophy (LVH) represents an important determinant of increased cardiovascular morbidity and mortality (CV) in end-stage renal disease (ESRD) patients. The role of inflammatory markers in pathogenesis of LVH in children with ESRD is not fully described. The aim of this study is to evaluate relation of some inflammatory markers [as hs C-reactive protein (hsCRP) and interleukin (IL) 18] with LVH in children with ESRD on regular hemodialysis (HD). This is a cross-sectional study performed on 50 children on regular HD. Demographic data were recorded. Echocardiography was performed at baseline to determine those with LVH. Biochemical parameters: hemoglobin (HB), hsCRP, IL 18, phosphorus, calcium, serum albumin, and lipid profile were evaluated and correlated with LVH. Data were analyzed using Student's t-test, and logistic regression to determine the relationship between LVH and other variables. LVH was present in 33 (66%) participants. Mean left ventricular mass index was 56.88 ± 22.23 g/m.2.7 Concentric remodeling, concentric hypertrophy, and eccentric hypertrophy were present in 4%, 22%, and 44% of the participants. In univariate analysis, children with LVH had significantly lower levels of HB and serum albumin but higher levels of hsCRP, and IL 18 compared to those without LVH. On multivariate analysis: only hsCRP, and IL 18 were significantly associated with LVH. This study shows that elevated hsCRP and IL-18 are independent determinants of LVH in HD children. Understanding the role of inflammatory molecules in the pathogenesis of LVH in ESRD is important for prediction of high-risk group and implementation of targeted anti-inflammatory therapies.

Evaluation of Serum Protein 14-3-3η (Eta) as a Novel Biomarker for Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is one of the most common systemic autoimmune diseases. New markers are needed for early diagnosis of RA as seronegativity in both early and established RA remains a major limitation of both anticitrullinated protein antibodies (ACPA) and rheumatoid factor (RF). The 14-3-3η protein may represent a novel biomarker for the detection of RA. We evaluated the diagnostic performance of serum 14-3-3η protein in early and established cases of rheumatoid arthritis and we compared the diagnostic accuracy of it with those of the well-known RA markers (e.g. RF and ACPA). Sera from 50 patients with RA (20 early and 30 established) based on the 2010 ACR / EULAR Rheumatoid Arthritis Classification Criteria, 15 patients with non-RA arthritis as diseases control group (8 patients with OA and 7 patients with SLE) and 14 healthy controls were enrolled in the study. Serum RF was determined by latex, ACPA and 14-3-3η protein were determined by ELISA. Serum 14-3-3η protein levels in patients with RA were significantly higher (P=0.001*) as compared to healthy individuals. For serum 14-3-3η diagnostic accuracy in RA; Receiver operating characteristic curves (ROC) analysis comparing patient with RA with healthy control showed AUC (0.916) at optimum cutoff of > 2.5ng/mL, and a sensitivity of 100%, a specificity of 78.57%, a PPV of 94.3, and an NPV of 100. No significant difference in 14-3-3η protein serum levels was found between early and established RA groups. It was positive in 100% of early and established RA patients who were seronegative for RF and ACPA. It is concluded that, 14-3-3η protein could improve the sensitivity of RA diagnosis and cover the shortage of detection of RF and ACPA in RA patients.