Ascitic calprotectin as a diagnostic marker for spontaneous bacterial peritonitis in hepatitis C virus cirrhotic Egyptian patients

Background The gold standard for the diagnosis of spontaneous bacterial peritonitis (SBP) is a polymorphonuclear leukocyte (PMNL) count of 250/mm3or more. Accurate and early diagnosis of SBP is important to decrease the mortality and complications in patients with cirrhosis. Aims The aim of this study was to evaluate the accuracy of ascitic fluid calprotectin as a diagnostic marker for the detection of SBP. Patients and methods Seventy Egyptian patients with liver cirrhosis and ascites were enrolled; these patients were divided into two groups: 50 patients with SBP and 20 patients with no SBP on the basis of an elevated ascitic PMNL count of 250 cells/mm3 or more. Ascitic samples were examined for PMNL count, culture, chemistry, and calprotectin concentrations in all patients. Results Calprotectin levels in ascitic fluid were correlated significantly with PMNLs and significantly higher in patients with SBP than non-SBP (P<0.001), with the best cutoff value for the detection of SBP of 783 ng/ml with a sensitivity, a specificity, a positive predictive value and negative predictive value, and an accuracy of 90, 100, 100, 80, and 92.9%, respectively. Conclusion Elevated ascitic calprotectin levels in cirrhotic patients are a diagnostic and reliable marker for the detection of SBP and considered a surrogate marker for PMNL

Clinical significance of serum interleukin-6 and −174 G/C promoter polymorphism in Rheumatoid arthritis patients

AbstractAim of the workTo evaluate the clinical significance of serum levels of interleukin-6 (IL-6) and −174 G/C promoter polymorphism in Rheumatoid arthritis (RA) patients.Patients and methodsWe studied 37 RA patients and 10 age and gender matched healthy controls. Demographic, clinical and serological data were prospectively evaluated. Disease activity score (DAS28) and Health Assessment Questionnaire (HAQ) were assessed. Serum IL-6 level was measured and promoter (−174G/C) genotyped.ResultsSerum IL-6 levels were significantly higher in RA patients compared to control (p=0.04), especially those with CC promoter polymorphism. Twenty-four patients had GG IL-6 (−174 G/C) gene promoter polymorphism, 11 were GC and 2 CC. Nine controls were GG and 1 GC. In patients with more advanced polymorphism (−174 CC) there was a significantly increased functional impairment (HAQ score) (p=0.029) and platelet count (p=0.049). In those with GG genotype, there was a significant correlation between IL-6 and Morning stiffness duration (r=0.44,p=0.03), while those with GC genotype had a significant negative correlation of the IL-6 level with the parameters of disease activity and the DAS28 (r=−0.69,p=0.019). None of the studied parameters would predict the IL-6 promoter polymorphism.ConclusionSerum IL-6 levels and −174 G/C promoter polymorphism were higher in RA patients than in healthy controls. The inverse relation of IL-6 with the DAS28 in those with an increased IL-6 promoter polymorphism may confirm its increased involvement in the pathogenesis of RA and in the increased disease activity which may point to the need for considering of anti-IL-6 agents in their management plan

Multigene Panel Sequencing Reveals Cancer-Specific and Common Somatic Mutations in Colorectal Cancer Patients: An Egyptian Experience

This study aims at identifying common pathogenic somatic mutations at different stages of colorectal carcinogenesis in Egyptian patients. Our cohort included colonoscopic biopsies collected from 120 patients: 20 biopsies from patients with inflammatory bowel disease, 38 from colonic polyp patients, and 62 from patients with colorectal cancer. On top of this, the cohort included 20 biopsies from patients with non-specific mild to moderated colitis. Targeted DNA sequencing using a customized gene panel of 96 colorectal related genes running on the Ion Torrent NGS technology was used to process the samples. Our results revealed that 69% of all cases harbored at least one somatic mutation. Fifty-seven genes were found to carry 232 somatic non-synonymous variants. The most frequently pathogenic somatic mutations were localized in TP53, APC, KRAS, and PIK3CA. In total, 16 somatic mutations were detected in the CRC group and in either the IBD or CP group. In addition, our data showed that 51% of total somatic variants were CRC-specific variants. The average number of CRC-specific variants per sample is 2.4. The top genes carrying CRC-specific mutations are APC, TP53, PIK3CA, FBXW7, ATM, and SMAD4. It seems obvious that TP53 and APC genes were the most affected genes with somatic mutations in all groups. Of interest, 85% and 28% of the APC and TP53 deleterious somatic mutations were located in Exon 14 and Exon 3, respectively. Besides, 37% and 28% of the total somatic mutations identified in APC and TP53 were CRC-specific variants, respectively. Moreover, we identified that, in 29 somatic mutations in 21 genes, their association with CRC patients was unprecedented. Ten detected variants were likely to be novel: six in PIK3CA and four variants in FBXW7. The detected P53, Wnt/&beta;catenin, Angiogenesis, EGFR, TGF-&beta; and Interleukin signaling pathways were the most altered pathways in 22%, 16%, 12%, 10%, 9% and 9% of the CRC patients, respectively. These results would contribute to a better understanding of the colorectal cancer and in introducing personalized therapies for Egyptian CRC patients