IntroductionHepatitis C virus (HCV) infection persists in most infected individuals and can lead to the development of chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) have a crucial role in various liver diseases, especially HCC. The expression profiles of circulating microRNAs have been studied aiming at the identification of novel non-invasive biomarkers. This study aims to develop a non-invasive diagnostic tool based on measuring the serum levels of different miRNAs in order to detect HCV-induced HCC at the early stages of the disease.Material and methodsFive main miRNAs (miRNA-122a, miRNA-125a, miRNA-139, miRNA-145, and miRNA-199a) were selected according to the literature that demonstrated their unique expression pattern during HCC development. Serum samples were collected from 42 cases of chronic hepatitis C (CHC) without cirrhosis, 45 cases of CHC with cirrhosis (LC), 38 cases of HCC with HCV, and 40 healthy individuals serving as a control. The five miRNAs were measured using real-time reverse transcription PCR. The conventional HCC markers α-fetoprotein (AFP) and des-γ-carboxyprothrombin (DCP) were measured with commercial kits.ResultsSerum levels of miRNA-122a, miRNA-125a, miRNA-139, miRNA-145, and miRNA-199a were significantly lower (p < 0.01) in HCC than in CHC and LC groups. As a single marker, miRNA-122a had the highest sensitivity for HCC, followed by miRNA-199a, miRNA-145, miRNA-139, and miRNA-125a.ConclusionsThese findings indicate that measurement of serum levels of miRNA-122a, miRNA-125a, miRNA-139, miRNA-145, and miRNA-199a can differentiate HCC from CHC and LC. Our results suggest that serum miR-122 might serve as a novel and potential noninvasive biomarker for HCV-induced HCC.

AimsWe prospectively studied the efficacy, incidence of adverse drug reactions and withdrawal from leflunomide in an outpatient population with rheumatoid arthritis in a setting of care-as-usual. MethodsIn this prospective case series study, from outpatient medical records a standard dataset was collected including patient and disease characteristics, data on leflunomide use and adverse drug reactions. ResultsDuring the study period 136 rheumatoid arthritis patients started leflunomide. Median (range) follow-up duration was 317 (11-911) days. Sixty-five percent of patients experienced at least one adverse drug reaction related to leflunomide. During followup 76 patients (56%) withdrew from leflunomide treatment, mainly because of adverse drug reactions (29%) or lack of efficacy (13%). The overall incidence density for withdrawal from leflunomide was 56.2 per 100 patient-years. Complete data for calculating efficacy using a validated disease activity score on 28 joints (DAS 28 ) was available for 48, 36, and 35% of patients at 2, 6, and 12 months follow-up, respectively. Within a 12-month period after start of leflunomide treatment 76% of the evaluable patients were classified as moderate or good responders according to the DAS 28 response criteria. ConclusionsIn the setting of care-as-usual, rheumatoid arthritis patients starting leflunomide frequently experienced adverse drug reactions. More than half of the patients withdrew from leflunomide treatment within a year after start of leflunomide treatment, mainly because of adverse drug reactions.

Aims  We prospectively studied the efficacy, incidence of adverse drug reactions and withdrawal from leflunomide in an outpatient population with rheumatoid arthritis in a setting of care‐as‐usual.Methods  In this prospective case series study, a standard dataset was collected from outpatient medical records, including patient and disease characteristics, data on leflunomide use and adverse drug reactions.Results  During the study period 136 rheumatoid arthritis patients started leflunomide. Median (range) follow‐up duration was 317 (11–911) days. Sixty‐five percent of patients experienced at least one adverse drug reaction related to leflunomide. During follow‐up 76 patients (56%) withdrew from leflunomide treatment, mainly because of adverse drug reactions (29%) or lack of efficacy (13%). The overall incidence density for withdrawal from leflunomide was 56.2 per 100 patient years. Complete data for calculating efficacy using a validated disease activity score on 28 joints (DAS28) was available for 48, 36, and 35% of patients at 2, 6, and 12 months follow‐up, respectively. Within a 12‐month period after start of leflunomide treatment 76% of the evaluable patients were classified as moderate or good responders according to the DAS28 response criteria.Conclusions  In the setting of care‐as‐usual rheumatoid arthritis patients starting leflunomide frequently experienced adverse drug reactions. More than half of the patients withdrew from leflunomide treatment within 1 year of starting leflunomide treatment, mainly because of adverse drug reactions.

The results indicated that the measurement of serum levels of miR-125a, miR-139, miR-145, and miR-199a can help to differentiate HCC from CHC and LC. Also, miR-16, miR-34a, and miR-221 serum levels would have a prognostic value. MiR-34a had the highest specificity and sensitivity, indicating that it might serve as a novel and potential non-invasive biomarker for HCV-induced HCC.

Extended-spectrum -lactamases (ESBLs) are plasmid encoded enzymes that confer resistance to -lactam antibiotics through the hydrolysis of the -lactam ring. ESBLs are distributed worldwide with an increasing incidence and prevalence in the Middle East due to the misuse of antibiotics and lack of coherent antimicrobial surveillance studies. The aim of study is to analyze molecularly the antimicrobial resistance mechanisms of 50 Escherichia coli and Klebsiella pneumoniae isolates from nosocomial infections in hospitalized patients in Oman. Screening for antimicrobial resistance (AR) and ESBL production was carried out with the disk diffusion and E-test methods following CLSI guidelines. ESBL producers were screened for bla CTX-M , bla SHV , and bla TEM resistance markers via PCR using gene-specific primers. All amplified PCR fragments will be sequenced to determine their allelic variants. In order to demonstrate the overall genotypic variation, Pulsed-Field Gel Electrophoresis (PFGE) analyses were done separately among all E. coli and K. pneumoniae isolates. According to the AR analysis, 82% (41/50) of isolates were determined to be ESBL producing bacteria. The percentages of isolates with genetic markers for bla CTX-M , bla SHV , and bla TEM were 73%, 24%, and 68%, respectively. Preliminary PFGE analyses demonstrated high level of variation among ESBL isolates compared to non-ESBL producers. Further surveillance studies are needed to describe better the AR situation in these hospitals in Oman.