Short-term effect of gluten-free diet on disease severity, quality of life, and inflammatory markers among patients with mild to moderate ulcerative colitis: A triple-blind randomized placebo-controlled trial.

BACKGROUND AND STUDY AIMS: Diet is an important underlying factor in ulcerative colitis (UC) disease. The present study aimed to investigate the effect of a gluten-free diet (GFD) on disease severity, quality of life, and inflammatory markers in patients with UC. PATIENTS AND METHODS: In this triple-blind randomized placebo-controlled clinical trial, we evaluated the effect of a GFD on the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), fecal calprotectin, disease severity, and quality of life in patients with mild to moderate UC. Patients' quality of life and severity of symptoms were evaluated using the Inflammatory Bowel Disease Questionnaire (IBDQ) and Simple Clinical Colitis Activity Index (SCCAI), respectively. Patients received this regimen for six weeks and were evaluated before and after the intervention. RESULTS: The mean age of patients (n = 26) was 39.31 years (standard deviation = 9.34). In both study groups, the mean ESR, CRP, IBDQ, and SCCAI showed no statistically significant improvement with the dietary intervention. Fecal calprotectin was increased in both groups without statistical significance. CONCLUSIONS: We could not find any significant effect of GFD on inflammatory markers, quality of life, and disease severity among patients with mild to moderate UC. It is too early to suggest the gluten-free diet as a safe and beneficial regimen for UC patients. There is a need for further investigations with larger sample sizes and longer follow-ups as clinical trials and cohort studies to obtain more reliable results.

Gene expression biomarkers differentiate overall survival of colorectal cancer upon targeted therapies.

While monoclonal antibody-based targeted therapies have substantially improved progression-free survival in cancer patients, the variability in individual responses poses a significant challenge in patient care. Therefore, identifying cancer subtypes and their associated biomarkers is required for assigning effective treatment. In this study, we integrated genotype and pre-treatment tissue RNA-seq data and identified biomarkers causally associated with the overall survival (OS) of colorectal cancer (CRC) patients treated with either cetuximab or bevacizumab. We performed enrichment analysis for specific consensus molecular subtypes (CMS) of colorectal cancer and evaluated differential expression of identified genes using paired tumor and normal tissue from an external cohort. In addition, we replicated the causal effect of these genes on OS using validation cohort and assessed their association with the Cancer Genome Atlas Program data as an external cohort. One of the replicated findings was WDR62, whose overexpression shortened OS of patients treated with cetuximab. Enrichment of its over expression in CMS1 and low expression in CMS4 suggests that patients with CMS4 subtype may drive greater benefit from cetuximab. In summary, this study highlights the importance of integrating different omics data for identifying promising biomarkers specific to a treatment or a cancer subtype.

Gene signatures derived from transcriptomic-causal networks stratified colorectal cancer patients for effective targeted therapy.

Predictive and prognostic gene signatures derived from interconnectivity among genes can tailor clinical care to patients in cancer treatment. We identified gene interconnectivity as the transcriptomic-causal network by integrating germline genotyping and tumor RNA-seq data from 1,165 patients with metastatic colorectal cancer (CRC). The patients were enrolled in a clinical trial with randomized treatment, either cetuximab or bevacizumab in combination with chemotherapy. We linked the network to overall survival (OS) and detected novel biomarkers by controlling for confounding genes. Our data-driven approach discerned sets of genes, each set collectively stratify patients based on OS. Two signatures under the cetuximab treatment were related to wound healing and macrophages. The signature under the bevacizumab treatment was related to cytotoxicity and we replicated its effect on OS using an external cohort. We also showed that the genes influencing OS within the signatures are downregulated in CRC tumor vs. normal tissue using another external cohort. Furthermore, the corresponding proteins encoded by the genes within the signatures interact each other and are functionally related. In conclusion, this study identified a group of genes that collectively stratified patients based on OS and uncovered promising novel prognostic biomarkers for personalized treatment of CRC using transcriptomic causal networks.

Female gender and Helicobacter pylori infection, the most important predisposition factors in a cohort of gastric cancer: A longitudinal study.

BACKGROUND: Gastric cancer (GC) is one of the most common Cancers in the world and Helicobacter pylori (HP) infection is considered a causative factor. The aim of this study was to determine the characteristics and the associated factors of (GC) in a small cohort. METHODS: Overall, 54 patients with diagnosed gastric cancer were followed-up at the Department of Gastroenterology & Hepatology at Baqiyatallah University of Medical Sciences. 37 (68.5%) of them were positive for H pylori infection in histopathological evaluations. Univariate and multivariate regression analyses were used to determine the associations of demographic features and HP infection status with GC characteristics and prognosis. RESULTS: Univariate analysis showed female gender (odds ratio (OR): 6.53; 95% confidence interval (95%CI): 1.59-26.8; P=0.008), and illiteracy (compared to intermediate education; OR: 5.9, 95%CI: 1.37-25.43; p=0.05) were associated significantly with higher rate of HP infection. After a mean±SD follow-up duration of 254±329 months, only female gender was significantly associated with HP infection in GC (OR:4.56; 95% CI: 1.0-21.76; P=0.05). H pylori positive patients had significantly higher grade of GC (OR: 3.97; 95% CI: 1.0-16.16; P=0.05), and a trend toward greater GC stage (OR: 4.46, 95% CI: 9.39-21.23; p=0.06). There was no association between survival rate and H pylori infection. CONCLUSION: In the current study, we found a significant association of female gender with GN and an association of higher grade of GC with female gender. These findings may indicate a sex disparity in susceptibility to HP infection regarding GC future studies of larger populations are recommended.

Occult HCV Infection: The Current State of Knowledge.

CONTEXT: Occult HCV infection (OCI) is defined as the presence of HCV-RNA in hepatocytes and the absence of HCV in the serum according to usual tests. We aimed to define OCI and provide information about the currently available diagnostic methods. Then we focus on specific groups that are at high risk of OCI and finally investigate immune responses to OCI and the available treatment approaches. EVIDENCE ACQUISITION: PubMed, Scopus and Google Scholar were comprehensively searched with combination of following keywords: "occult", "hepatitis C virus" and "occult HCV infection". The definition of OCI, diagnostic methods, specific groups that are at high risk and available treatment approaches were extract from literature. An analysis of available articles on OCI also was done based on Scopus search results. RESULTS: OCI has been reported in several high-risk groups, especially in hemodialysis patients and subjects with cryptogenic liver disease. Furthermore, some studies have proposed a specific immune response for OCI in comparison with chronic hepatitis C (CHC). CONCLUSIONS: With a clinical history of approximately 11 years, occult HCV infection can be considered an occult type of CHC. Evidences suggest that considering OCI in these high-risk groups seems to be necessary. We suggest that alternative diagnostic tests should be applied and that there is a need for the participation of all countries to determine the epidemiology of this type of HCV infection. Additionally, evaluating OCI in blood transfusion centers and in patients who receive large amounts of blood and clotting factors, such as patients with hemophilia, should be performed in future projects.

Unfavorable survival rates in Iranian patients with gastric cancers: a single center experience from Tehran.

We examined the effect of potential interfering factors that play major roles in the outcome of our patients with stomach cancer. 100 consecutive patients diagnosed with gastric cancers were prospectively observed, treated and followed from November 2009 to January. Absence of Helicobacter pylori infection (P=0.027), absence of vascularisation (P<0.001), and undetermined histopathological type of adenocarcinoma (P=0.003) were factors significantly associated with higher grade of gastric lesions. Life tables were used to define survival of gastric cancers. Survival rates of these patients at 1st week, 1st month, 2nd month, 3rd month, and 6th month were 97%, 96%, 91%, 90%, and 82%, respectively. The only determinant of 6 months of survival was age over 68 (P=0.039). Our study confirms our previous knowledge that gastric cancers have unfavorable outcome in Iran.

Magnetic resonance imaging findings in epileptic children and its relation to clinical and demographic findings.

Epilepsy is an important disease with a cumulative incidence of 3% all over the life and more than half of them are started from childhood. In this study we surveyed magnetic resonance imaging (MRI) findings in epileptic children and its relation with clinical and demographic findings in order to find better diagnostic and treatment modalities for these children in the future. In this cross sectional study, we investigated consecutively all 1 to 15-year-old epileptic children who referred to the pediatric neurology outpatient clinic from 2004 to 2010. Two hundred children were enrolled for investigation. There were 85 (42.5%) girls and 115 (57.7%) boys, aged 1 to 15-year-old (7.7 ± 4). 196 (98%) of the children had abnormal electroencephalography (EEG). Abnormal MRI was seen in 57 (28.5%) patients and consisted of brain atrophy (10%), increasing white matter signal intensity in T2-weighted images (8%), benign cysts (5%), brain tumors (4%) and vascular abnormalities (1.5%). Abnormal MRI findings had significant relation with abnormal EEG, age, positive family history for epilepsy, dysmorphic appearance, and abnormal physical exam. Considering 98% EEG abnormalities in these epileptic children, benign nature of MRI findings in most of our cases, the high price of MRI and the small minority of patients who benefit from active intervention as a result of MRI, we suggest to use EEG for confirmation of epilepsy and perform MRI for patient with abnormal physical exams, focal neurologic deficits or focal EEG abnormalities.

Elevated alanine aminotransferase activity is not associated with dyslipidemias, but related to insulin resistance and higher disease grades in non-diabetic non-alcoholic fatty liver disease.

OBJECTIVE: To explore demographic and metabolic factors associated with increased alanine aminotransferase (ALT) activity in non-diabetic non-alcoholic fatty liver disease (NAFLD) patients. METHODS: Overall 372 patients who consecutively attended to Gastroenterology Clinic of Baqiyatallah University of Medical Sciences, Tehran, Iran awere diagnosed as NAFLD entered into analysis. Exclusion criteria were having diabetes mellitus and fasting blood glucose over 126 mg/dL, active hepatitis B virus infection, having hepatitis C virus positive serology, and to be under corticosteroid therapy. ALT levels were considered pathologically high when it was over 30 IU/L for men and over 19 IU/L for women. RESULTS: Bivariate analyses using t test and chi-square test showed that patients with pathologically augmented ALT levels had significantly higher NAFLD grades in their ultrasonographic evaluations (P=0.003). Moreover, these patients represented significantly higher homeostatic model assessment levels (P=0.003), levels of serum insulin (P=0.002), fasting blood glucose (P<0.001), and uric acid (P=0.02). The prevalence of insulin resistance was also higher in patients with increased serum ALT concentrations. Multifactorial logistic regression models showed that ultrasonographic grading of NAFLD (P=0.027) and insulin resistance (P=0.013) were the only variables significantly associated with abnormal ALT levels. CONCLUSIONS: This study shows that the associations of increased ALT serum levels in NAFLD patients are different from what are supposed before. By excluding diabetic patients from our population, we find that increased ALT levels are not associated with dyslipidemias but are independently associated with insulin resistance and NAFLD grading on ultrasonographic evaluations. Further studies are needed to confirm our results.