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BACKGROUND Increases in aminotransferases (transaminitis) are potential major adverse reactions seen with long-term use of methotrexate (MTX). The aim of this study, therefore was to evaluate the incidence of MTX induced hepatotoxicity and its risk factors among rheumatoid arthritis (RA) patients. METHODS This retrospective study described 286 patients with RA who received ≥ 7.5 mg MTX weekly in an academic rheumatology clinic over a 15 year period. The results of serial liver function tests, concurrent MTX dose, cumulative dose and use of hepatotoxic drugs were collected and statistically analyzed according to a consecutive elevation in aminotransferases which occurred over at least a two week interval. RESULTS During the study period, 286 patients (84.4% female) with mean age of 46.6±12.7 years (18-84 years) were enrolled. Transaminitis occurred among 23.7% of patients (incidence: 6.9 per 100 person-years) during 40.5±34.6 month's exposure to MTX (989.6 person-years). The time difference between onset of therapy and occurrence of transaminitis was 22.1±22.0 months. The only significant factor related to the occurrence of transaminitis was the duration of MTX therapy. The average duration of treatment among patients with transaminitis (59.6±42.3 months) was greater than those with no transaminitis (p

Post-operative recurrence is a critical issue in the surveillance of Crohn's disease after ileocecal resection. This meta-analysis aims to assess the diagnostic yield of enterography techniques in post-operative recurrence of Crohn's disease. A systematic electronic bibliographic databases search was conducted. The inclusion criteria of original articles were: Utilized MR enterography or CT enterography after ileocolonic resection; Documented recurrence by ileo-colonoscopy (Rutgeerts' score ≥ i2); Provided crude data of diagnostic performance. A random-effect method was used for analysis. Relative risk and diagnostic value of each imaging feature were calculated. Eleven studies (11 populations and 589 patients) were included (4 CTE and 7 MRE with 248 and 341 patients, respectively). The pooled sensitivity and specificity of the enterography were 91% (95% CI: 0.85-0.95) and 75% (95% CI: 0.56-0.87), respectively. The pooled sensitivity and specificity of CTE were 93% (95% CI: 0.87-0.96) and 67% (95% CI: 0.35-0.90), respectively. MRE revealed pooled sensitivity and specificity of 90% (95% CI: 0.78-0.96) and 78% (95% CI: 0.57-0.90), respectively. The inter-study heterogeneity was low for sensitivity (I 2  = 29%, p-value = 0.17) and high for specificity (I 2  = 85%, p-value < 0.01). Wall enhancement, anastomosis wall thickening, anastomosis stenosis, pre-anastomotic dilatation, penetrating lesion, comb sign, and perivisceral edema were significantly higher in POR patients. Wall thickening and penetrating lesion were the most sensitive (81%) and specific (97%) findings, respectively. MRE and CTE exhibit high sensitivity and acceptable specificity (especially MRE) for detection of recurrence in Crohn's disease which makes them an effective initial screening tool and reserves ileo-colonoscopy for those patients with inconclusive enterography results., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Data on the epidemiology of inflammatory bowel disease (IBD) in the Middle East are scarce. We aimed to describe the clinical phenotype, disease course, and medication usage of IBD cases from Iran in the Middle East., Methods: We conducted a cross-sectional study of registered IBD patients in the Iranian Registry of Crohn's and Colitis (IRCC) from 2017 until 2022. We collected information on demographic characteristics, past medical history, family history, disease extent and location, extra-intestinal manifestations, IBD medications, and activity using the IBD-control-8 questionnaire and the Manitoba IBD index, admissions history, history of colon cancer, and IBD-related surgeries., Results: In total, 9746 patients with ulcerative colitis (UC) (n=7793), and Crohn's disease (CD) (n=1953) were reported. The UC to CD ratio was 3.99. The median age at diagnosis was 29.2 (IQR: 22.6,37.6) and 27.6 (IQR: 20.6,37.6) for patients with UC and CD, respectively. The male-to-female ratio was 1.28 in CD patients. A positive family history was observed in 17.9% of UC patients. The majority of UC patients had pancolitis (47%). Ileocolonic involvement was the most common type of involvement in CD patients (43.7%), and the prevalence of stricturing behavior was 4.6%. A prevalence of 0.3% was observed for colorectal cancer among patients with UC. Moreover,15.2% of UC patients and 38.4% of CD patients had been treated with anti-tumor necrosis factor (anti-TNF)., Conclusion: In this national registry-based study, there are significant differences in some clinical phenotypes such as the prevalence of extra-intestinal manifestations and treatment strategies such as biological use in different geographical locations., (© 2024 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Background: It is unknown if the clinical manifestations and phenotype of disease are comparable between early- and elderly-onset inflammatory bowel disease (IBD). We aimed to seek differences in disease phenotype, course, complications, and treatment between early- and elderly-onset IBD patients., Methods: This retrospective cohort study on registered IBD patients in the Iranian Registry of Crohn's and Colitis (IRCC) compared demographics, disease phenotype, disease activity, IBD-related surgery and medications between early- and elderly-onset IBD. A generalized linear regression model was used to investigate the relative risk of age at diagnosis adjusted for gender and disease duration for the outcomes., Results: From 10048 IBD patients, 749 with early-onset (7.5%), and 472 (4.7%) elderly-onset IBD were enrolled: 855 (63.1%) ulcerative colitis (UC) and 366 (26.9%) Crohn's disease (CD). Left-sided colitis was more frequent among elderly-onset UC patients ( P <0.001). Ileum and ileocolonic locations were the most common types in elderly-onset and early-onset CD patients, respectively. In comparison with elderly-onset UC, early-onset cases more often used prednisolone (22.1% vs. 11.4%, P =0.001), immunomodulators (44.9% vs 25.2%, P <0.001) and anti-tumor necrosis factors (TNF) (20.1% vs 11.9%, P =0.002). Elderly-onset UC patients had 0.7 times lower risk of aggressive phenotype (95%CI:0.6‒0.9, P =0.005). Early-onset CD was associated with higher use of prednisolone (27.7% vs 8.1%, P <0.001), immunomodulators (58.7% vs 41.8%, P =0.005) and anti-TNF (49.6% vs 35.4%, P =0.006)., Conclusion: Early-onset IBD was associated with a more aggressive phenotype and higher prednisolone, immunomodulators, and anti-TNF use., (© 2023 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Purpose: Given the association of inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC), we aimed to investigate the clinical relevance of abnormal hepatobiliary findings on magnetic resonance enterography (MRE) of IBD patients considering the risk of over- or underestimation of PSC at MRE., Material and Methods: Using the MRE dataset of patients referring to a tertiary hospital and the National Registry of Crohn's and Colitis, 69 MREs, including 23 IBD-PSC, 23 IBD-without PSC, and 23 healthy controls (HC), were retrospectively reviewed by 2 experienced radiologists blinded to the clinical data, to evaluate hepatobiliary abnormalities. Sensitivity, specificity, and likelihood ratios were calculated., Results: Bile duct irregularities were the most common finding in the IBD-PSC group, with a frequency of 91%. Intra- and extrahepatic bile duct (IHBD and EHBD) irregularities were observed in 87% and 78% of PSC patients, respectively. Higher frequency of IHBD and EHBD wall thickening, bile duct dilation, EHBD stricture, and periportal oedema were observed in the IBD-PSC group. Peribiliary T2-weighted hyperintensities and contrast-enhancement were significantly more common in the IBD-PSC group than in the IBD and HC groups (48% and 35%, respectively) ( p < 0.001). Detection of biliary irregularities on MRE had a specificity of 94% (95% CI: 82-99%), a sensitivity of 91% (95% CI: 72-99%), and a positive likelihood ratio of 14.0 (95% CI: 4.7-42.1) for the diagnosis of PSC., Conclusions: This study emphasizes the importance of assessing and reporting hepatobiliary abnormalities visible in the MRE of patients with IBD to avoid a delayed diagnosis of PSC., Competing Interests: Authors declare no conflict of interest., (© Pol J Radiol 2022.)

Background: The role of genetic and environmental factors in inflammatory bowel disease's (IBD) clinical course is not fully clear. We aimed to assess the clinical phenotype, disease course, and prognosis of familial IBD in comparison with sporadic cases., Methods: We conducted a prospective national matched case-control study of registered IBD patients in the Iranian Registry of Crohn's and Colitis (IRCC) recruited from 2017 until 2020. Sporadic and familial IBD patients were matched based on age, sex, and disease duration. Data on demographics, past medical disease, family history of IBD, disease type, clinical phenotype, extraintestinal manifestations, IBD medications, IBD activity using the IBD-control-8 questionnaire and the Manitoba IBD index, emergency visits in the past 12 months, admissions in the past 3 months, history of colon cancer, IBD-related surgeries, and aggressive phenotype were gathered. Variable distributions were compared between sporadic and familial cases., Results: Overall, 5231 patients with ulcerative colitis (UC, 18.3% familial) and 1438 patients with Crohn's disease (CD, 16.7% familial) were registered in the IRCC. Age at diagnosis was similar between familial and sporadic cases. After matching, 3523 UC patients and 908 CD patients were enrolled in the study. Extraintestinal manifestations, UC extent, CD location and behavior, anti-TNF use, disease activity, colon cancer, IBD-related surgeries and the aggressive phenotype were similar between these sporadic and familial cases., Conclusions: The prevalence of familial UC and CD cases in Iran was more similar to western countries, and family history did not show a predictive value for disease phenotype, course, and outcomes in our study., (© 2021 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To Evaluate the diagnostic performance of magnetic resonance enterography (MRE) for detecting colonic involvement of Crohn's disease (CD)., Materials and Methods: A systematic search of the electronic bibliographic databases was conducted. The inclusion criteria of published original articles were: (1) Utilized MRE to evaluate colon; (2) Patients with documented CD by colonoscopy; (3) Provided crude data of diagnostic performance in the large bowel; (4) Performed segmental evaluation. The colorectal segments were defined as the right colon, transverse colon, left colon, and rectum. A hierarchical bivariate method was used for analysis., Results: Eleven articles (12 populations and 987 patients) were included. The pooled sensitivity and specificity of the studies were 69% (95% CI: 0.52-0.82) and 95% (95% CI:0.92-0.97), respectively (AUC = 0.95). The pooled positive and negative likelihood ratios were 14 (95% CI:7.5-26.3) and 0.31 (95% CI:0.19-0.51), respectively. Regarding segments, the left colon had the highest sensitivity (60%) and lowest specificity (92%), while the transverse colon showed lowest sensitivity (49%) and highest specificity (95%). Comparing the age groups, MRE sensitivity and specificity was 80% and 95%, versus 62% and 94%, in pediatrics and adults respectively., Conclusion: MRE has a high specificity to detect colon pathologies in CD, while the sensitivity is low. Therefore, the test has a high value to rule in CD, while negative results are not sufficient to rule it out. Meanwhile, considering the higher sensitivity rate of the test in pediatrics, it has the potential to be used as a first-line investigation., (Copyright © 2021 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: COVID-19 has caused great concern for patients with underlying medical conditions. We aimed to determine the prognosis of patients with current or previous cancer with either a PCR-confirmed COVID-19 infection or a probable diagnosis according to chest CT scan., Methods: We conducted a case control study in a referral hospital on confirmed COVID-19 adult patients with and without a history of cancer from February 25th to April 21st , 2020. Patients were matched according to age, gender, and underlying diseases including ischemic heart disease (IHD), diabetes mellitus (DM), and hypertension (HTN). Demographic features, clinical data, comorbidities, symptoms, vital signs, laboratory findings, and chest computed tomography (CT) images have been extracted from patients' medical records. Multivariable logistic regression was used to estimate odd ratios and 95% confidence intervals of each factor of interest with outcomes., Results: Fifty-three confirmed COVID-19 patients with history of cancer were recruited and compared with 106 non-cancerous COVID-19 patients as controls. Male to female ratio was 1.33 and 45% were older than 65. Dyspnea and fever were the most common presenting symptoms in our population with 57.86 and 52.83% respectively. Moreover, dyspnea was significantly associated with an increased rate of mortality in the cancer subgroup (p = 0.013). Twenty-six patients (49%) survived among the cancer group while 89 patients (84%) survived in control (p = 0.000). in cancer group, patients with hematologic cancer had 63% mortality while patients with solid tumors had 37%. multivariate analysis model for survival prediction showed that history of cancer, impaired consciousness level, tachypnea, tachycardia, leukocytosis and thrombocytopenia were associated with an increased risk of death., Conclusion: In our study, cancer increased the mortality rate and hospital stay of COVID-19 patients and this effect remains significant after adjustment of confounders. Compared to solid tumors, hematologic malignancies have been associated with worse consequences and higher mortality rate. Clinical and para-clinical indicators were not appropriate to predict death in these patients.

BACKGROUND Measuring serum alanine aminotransferase (ALT) enzyme is a routine clinical test commonly used to evaluate abnormalities in the body in general, and in the liver function in particular. Higher ALT levels are associated with some metabolic disorders. The upper limit normal (ULN) is considered as a reliable threshold for the definition of high ALT., Objectives: To assess the existing evidence on the ULN for ALT in the general population., Data Source: PubMed (Medline), EMBASE, Scopus, and Web of Science (ISI) were searched using a specified search strategy., Eligibility Criteria: We collected documents published from 1980 to 2018 in the English language, focusing on human samples at the population level and extracted the data after qualitative evaluation. METHODS We conducted this study in accordance with the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. We used specific search terms and their combinations to find documents from relevant databases. We used a snowballing approach to find documents not captured in the main phase of the search. Two authors separately conducted the search, screened the articles, and selected documents that were qualified for data extraction based on the defined inclusion criteria. Finally, data extraction was conducted by two authors using PRISMA checklist. Reported ULNs for ALT and 95% confidence intervals (CIs) were documented in previously developed datasheets. RESULTS Out of 15242 studies, 47 articles were included for data extraction and analysis. Data were sparse and lacked the consistency to precisely estimate ULN for serum ALT. The ULN of ALT was significantly diverse across various geographical locations and sexes. The lowest value of ULN for ALT was 19 IU/L in Chinese children (age range: 7 to < 10 years), and the highest value of ULN for ALT was 55 IU/L in children from Ghana aged < 5 years., Limitations: The main limitation of the current systematic review was the scarcity of the reported measures for ULN of ALT. CONCLUSION Based on the results of the current systematic review, it is suggested that the normal range of ALT be redefined, but this redefinition should be done according to the localized data. In order to redefine the ULN for ALT, regional differences, methods used in ALT measurements, and ULN determination should be considered., Competing Interests: CONFLICT OF INTEREST The authors declare no conflict of interest related to this work., (© 2020 The Author(s).)

Background: It is increasingly common to collect and store specimens for future unspecified research. However, the effects of prolonged storage on the stability and quality of analytes in serum have not been well investigated. We aimed to determine whether the stability of liver enzymes extracted from frozen bio-samples stored at the baseline is affected by storage conditions., Methods: A total of four liver enzymes in the sera of 400 patients were examined following storage. After deter-mining the baseline measurements, the serum of each patient was aliquoted and stored at -70°C for three and six months, as well as one, two, and five years after collecting the original sample. The percent change from baseline measurements was calculated both statistically and clinically. Linear models were also used to correct the results of the samples based on the time they were frozen., Results: In almost all samples, liver enzymes were detectable until two years after the baseline, while in a signifi-cant proportion of samples, enzymes were not ultimately detectable five years after the baseline. Linear regression analysis on log-transformed levels of enzymes shows that the performance is acceptable until one year after the baseline. The performance of the prediction model declines substantially two and five years after the baseline, except for GGT., Conclusion: Long-term storage of serum samples significantly decreases the concentration of the liver enzymes from the baseline, except for GGT. It is not recommended to store samples for more than two years, as liver en-zymes are not detectable afterwards., (© 2020 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Background: Proton pump inhibitors (PPIs) with lipophilic nature may interact with lipid components of H. pylori cell membrane, disrupting cell structure and viability. In this study, the effect of PPIs on fatty acid and cholesterol components of H. pylori cell membrane was assessed., Methods: One H. pylori isolate was treated with 1X and 2X MICs (μg/mL) of lansoprazole (LPZ: 8 and 16) and pantoprazole (PAN: 128 and 256) in brain heart infusion broth plus serum. Treated H. pylori was cultured on brucella blood agar (BBA) and tetrazolium egg yolk agar (TEYA). Bacterial cells stained with Live/Dead kit were examined by fluorescent microscopy. Fatty acid and cholesterol contents of treated H. pylori were measured by gas chromatography., Results: PPI-treated H. pylori did not grow on BBA but grew on TEYA. Fluorescent microscopy showed H. pylori stained red. Analyses showed high frequency of saturated fatty acids, C14:0, C16:0 and C18:0. Among unsaturated fatty acids, C18:1 and C18:2c were increased, while five were eliminated and five were synthesized de novo. Cholesteryl-6-O-tetradecanoyl-α-D- glucopyranoside was detected as the only glycosylated cholesterol in treated H. pylori. Growth of PPI-treated H. pylori on cholesterol-rich TEYA showed that occurrence of cholesterol can reverse the growth inhibition by PPIs. Red- bacilli form of H. pylori showed dye entry through damaged cell membrane without lysis., Conclusion: Incorporation of lipophilic PPI into H. pylori cell membrane disrupted lipids and inhibited growth. However, H. pylori adjusted the defected membrane by replacing the lipid components and resisted lysis., (© 2020 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Vacuole of eukaryotic cells, beyond intracellular digestion plays additional roles such as storage of nutrients that provide favorable conditions for bacterial survival. In this study, occurrence of H. pylori inside the vacuole of Candida yeast was studied and the role of vacuolating cytotoxin A (VacA) in constructing the vacuole was discussed. One gastric Candida yeast was used for Live/Dead stain and fluorescence in situ hybridization (FISH) with universal bacterial probe. Yeast total DNA was used for amplification of full-length bacterial 16S rDNA as well as H. pylori-specific 16S rDNA and vacA alleles. Vacuoles were isolated from yeast cells and stained with fluorescent yeast vacuole membrane marker MDY-64. DNA extracted from vacuoles was used for amplification of H. pylori-specific 16S rDNA. Fluorescent microscopy showed occurrence of viable bacteria inside the vacuole of intact Candida yeast cells. FISH showed intracellular bacteria as fluorescent spots inside the vacuole of mother and daughter yeast cells, suggesting bacterial transmission to next generations of yeast. Sequencing of amplified products of bacterial 16S rDNA and amplification of H. pylori 16S rDNA and vacA confirmed the identity of intracellular bacteria as H. pylori. Isolated vacuoles were stained with membrane-specific marker and H. pylori 16S rDNA was amplified from their DNA content. Results of this study suggest yeast vacuole as a specialized niche for H. pylori. It appears that sequestration inside the vacuole may enhance bacterial survival., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: To assess small bowel abnormalities on magnetic resonance enterography (MRE) in adult patients with nonresponsive celiac disease (CD) and investigate their associations with endoscopic, histopathologic, serologic, and genetic features., Materials and Methods: This prospective study was carried out between September 2012 and August 2013. After approval by the Ethics Committee of our institution, informed consent was acquired from all participants. Forty consecutive patients with nonresponsive CD, aged 17-76 years, underwent MRE using a 1.5T unit. Sequences included T 2 -HASTE, True-FISP, pre- and postcontrast VIBE to assess the quantitative (number of ileal and jejunal folds) and qualitative (fold pattern abnormalities, mural thickening, increased enhancement, bowel dilatation, or intussusception) measures. Endoscopic manifestations were categorized as normal/mild vs. severe. Histopathological results were divided into mild and severe. Genotyping of HLA-DQ2 and DQ8 was performed. Serum levels of tissue-transglutaminase, endomysial, and gliadin antibodies were also determined. Logistic regression analysis and receiver operating characteristic (ROC) curve were used., Results: Twenty-nine (72.5%) cases showed abnormal MRE. Reversed jejunoileal fold pattern had significant association with severe endoscopic (odds ratio [OR] = 8.38, 95% confidence interval [CI] 1.73-40.5) and pathologic features (OR = 7.36, 95% CI 1.33-40.54). An increased number of ileal folds/inch was significantly associated with severe MARSH score and positive HLA-DQ8. (P < 0.001 and P = 0.026, respectively). Ileal fold number had the highest areas under the curve for prediction of severe endoscopic (AUC: 0.75, P = 0.009) and pathologic (AUC: 0.84, P < 0.001) findings and positive anti-transglutaminase antibody (AUC: 0.85, P = 0.027)., Conclusion: Fold pattern reversal on MRE is highly associated with endoscopic and pathologic features of refractory celiac disease (RCD). Increased ileal folds showed higher correlation with endoscopic-pathologic features, HLA-DQ8, and anti-transglutaminase level. MRE might be more sensitive for detection of increased ileal folds in CD rather than reduction of duodenal and jejunal folds due to better distension of ileal loops., Level of Evidence: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1096-1106., (© 2017 International Society for Magnetic Resonance in Medicine.)

Background: Recent data has proven that the WHO (world health organization) cut-off for obesity is not applicable to the Asian population. This study aims to estimate the prevalence of lean NAFLD (non-alcoholic fatty liver disease) in the capital of Iran and extract probable predictors for this growing health issue in this population., Methods: This is a population-based cross-sectional study on apparently healthy subjects over 18 years of age. The participants were interviewed for baseline demographic and clinical information. They were subsequently referred for physical examination and blood sampling. NAFLD was diagnosed using abdominal ultrasonography by a single expert radiologist., Results: Of 927 eligible participants who entered the study, 314 were lean; BMI (body mass index) <25 kg/m2. The prevalence of NAFLD was 17.52% (95% Exact CI: 13.48%-22.18%). BMI, SBP (systolic blood pressure), DBP (diastolic blood pressure), total cholesterol, HDL (high-density lipoprotein), LDL (low-density lipoprotein) and triglyceride were significantly different in patients with NAFLD. In the final multiple analysis, higher levels of triglyceride, upper SBP and higher BMI even in the range of less than 25 kg/m2 were independent predictors of NAFLD in lean participants. In lean participants with more components of metabolic syndrome, the prevalence of NAFLD increased significantly (all P < 0.01). BMI cut-offs in men and women along with waist circumference cut-off in men could significantly predict the presence of NAFLD in lean patients. After comparing these values, McNemar test showed that BMI cut-offs are more robust than waist circumference cut-offs for predicting the presence of NAFLD in lean subjects (P < 0.01)., Conclusion: The prevalence of NAFLD in lean subjects in a sample of Iranian population is 17.52%. Hypertriglyceridemia, higher SBP, and higher BMI especially over 23.2 are independent factors associated with the presence of NAFLD in lean subjects.

BACKGROUND Intestinal mast cells may cause gastrointestinal symptoms in patients with diarrhea-dominant irritable bowel syndrome (IBS). The objective of this study was to determine the effect of mesalazine on the number of lamina propria mast cells and clinical manifestations of patients with diarrhea-dominant IBS referred to Shariati Hospital affiliated to Tehran University of Medical Sciences. METHODS This was a randomized placebo-controlled double-blind trial conducted on 49 patients with diarrhea-dominant IBS. The patients were randomly assigned to one of the experiment or control groups. The patients in experiment group took 2400 mg mesalazine daily in three divided doses for 8 weeks and the patient in control group took placebo on the same basis. Our first targeted outcome was an assigned downturn of mast cells number to the safe colonic baseline and the next one was a marked palliation of disease symptoms. Data were analyzed conforming intention-to-treat method. We used MANCOVA test to compare our both assigned outcomes in the two groups. We also compared the data with baseline values in both groups.All statistical tests were performed at the significance level of 0.05. RESULTS There was no significant difference between Mesalazine and placebo groups regarding the number of mast cells ( p value=0.396), abdominal pain ( p value=0.054), bloating ( p value=0.365), defecation urgency ( p value=0.212), and defecation frequency ( p value=0.702). CONCLUSION Mesalazine had no significant effect either on the number of mast cells or on the severity of disease symptoms. This finding seems to be inconsistent with the hypothesis indicating immune mechanisms as potential therapeutic targets in IBS. The possible difference in this effect of Mesalazine should be evaluated in further studies among populations varying in race, ethnic, and geographical characteristics., Competing Interests: CONFLICT OF INTEREST The authors declare no conflict of interest related to this work

The indexed Iranian journals in ISI and PubMed at the end of 2012 with known impact factor (IF) were evaluated with regard to the number of articles published in 2010-2012, the number of citations by authors from inside and outside Iran, their IF as well as their ranking order among all other journals in their specialized categories. There were among 130 English journals, 21 indexed with known IF. The mean IF of these journals increased from 0.4 in 2010 to 0.68 in 2012. The number of citations per article by authors from outside Iran increased from 0.19 to 0.49 during the same time period. The rank of the majority of the indexed journals was in the lowest 20% of their category. Although some improvement has been observed in the quality and the number of citations of Iranian journals indexed in ISI during these two years, the quality of the manuscripts remains low. A reduction in the number of journals, a change of their structure as well as more financial resources for research is necessary for the improvement of the quality and better rank and status of Iranian science among an international audience.

BACKGROUND The cause of common bile duct (CBD) dilatation cannot be determined by imaging modalities in many patients. The aim of this study was to assess the value of endoscopic ultrasonography (EUS) in detecting the cause of CBD dilatation in patients in whom ultrasonography could not demonstrate the cause of dilation. METHODS Prospectively, 152 consecutive patients who were referred for evaluation of dilated CBD (diameter ≥7 mm) of undetermined origin by ultrasonography were included in this study. All the patients underwent EUS. Final diagnoses were determined by using endoscopic retrograde cholangiopancreatography (ERCP), EUS-guided fine needle aspiration (FNA), surgical exploration, or follow-up for at least 10 months. Patients with choledocholithiasis were referred for ERCP and sphincterotomy, and patients with operable tumors were referred for surgery.Patients with inoperable tumors underwent biliary stenting with or without tchemoradiotherapy. RESULTS 152 patients (54% female) with dilated CBD were included. Mean (±SD) age of the patients was 60.4 (±17.3) years. The mean CBD diameter for all study group in transabdominal ultrasonography and EUS were 11.7 millimeter and 10.1 millimeter, respectively. Most of the patients with dilated CBD and abnormal liver function test (LFT) had an important finding in EUS and follow-up diagnosis including peri-ampullary tumors. Mean diameter of CBD in patients with and without abnormal LFT were 10.5 IU/L and 12.1 IU/L, respectively. Final diagnoses included choledocholithiasis in 32 (21.1%),passed CBD stone in 35 (23%), opium-induced CBD dilation in 14 (9.2%), post-cholecystectomy states in 20 (13.1%), ampullary adenoma/carcinoma in 15 (15.8%), cholangiocarcinoma in 14 (9.2%), and pancreatic head cancer in9 (5.9%) patients. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of EUS for patients with abnormal EUS were 89.5%, 100.0%, 100.0%, 91.2%, and 90.9%, respectively. CONCLUSION After diagnosis of CBD dilation by transabdominal ultrasonography, EUS may be a reasonable choice for determining the etiology of dilated CBD and tumor staging.

BACKGROUND This study is the first study to evaluate the nonadherence rate and reasons of same patient with inflammatory bowel disease (IBD) in Iran. METHODS During 9 months, 500 patients with IBD were enrolled in the study. Patients were interviewed about their nonadherence behaviors. Factor analysis was used to analyze the collected answers. RESULTS The overall rate of nonadherence was 33.3% (27.6% intentional nonadherence and 5.7% unintentional nonadherence). 33.6% of the patients had at least one relapse after discontinuing treatment. The most frequent reason for intentional nonadherence was discontinuing the treatment after recovering from symptoms (42.7%). The most frequent reason for unintentional nonadherence was forgetfulness (5.2%). 19.8% of the patients did not visit their gastroenterologist on time and they purchased drugs from the drugstore. These patients reported that their clinics were too far and difficult to access. There was no significant relationship between nonadherence and demographic variables. CONCLUSION Multiple reasons are suggested as factors of medication nonadherence and they seem to be different among different populations. Determining these possible reasons, could lead to finding suitable strategies to overcome or reduce them.

BACKGROUND In some studies inflammatory bowel disease (IBD) and celiac disease were considered to be associated and some belive that this association may influence the prognosis of IBD. However, there is a cosiderable controversy regarding this association. Therefore ,we aimed to assess the association of these two common digestive diseases and evaluate the complications of this association. METHODS In this comparative study, 200 patients with ulceritive colitis (UC) and 206 patients with Crohn's disease (CD) were evaluated for celiac disease using relevant diagnostic tests and pathologic studies. Total IgA, IgA tissue transgulaminase antibody and specific IgA anti endomysial antibody were asseyed. In cases of IgA deficiency, total IgG and IgG tissue TG and IgG anti endomyseal Ab were measured. Patients with increased specific IgA and IgG antibodies for celiac disease, underwent endoscopy and 4 standard samples were obtained. Our results were compared with the results of the prevalence study of celiac disease in the general population. Data were analyzed using analytic and descriptive statistics at a significance level of 5%. RESULTS Among the studied patients, 1 patient with UC had elevated IgA anti tTG antibody and IgA anti-endomysial antibody who underwent endoscopy and celiac was confirmed on pathology. Hence, of the 200 patientswith UC, the diagnosis of celiac disease was confirmed in 1 patient (1:200) with no significant difference with the prevalence of celiac disease in the general population (1:166). However, none of our patients with Crohn's disease had celiac disease (0:206). CONCLUSION We found no significant difference in the prevalence of celiac disease between patients with UC and the general population. Since most of our participants had a mild level of Crohn's activation, none of those with Crohn's disease had celiac disease. Complications of IBD including sclerosing cholangitis, may be more common in patients with concurrent celiac disease. Therefore, it is recommended that celiac disease be considered in patients with severe and complicated IBD.

Purpose: This study investigated how the volume of hepatic metastatic lesions can affect liver haemodynamics and whether these perfusion parameters may help to differentiate benign and malignant liver lesions., Materials and Methods: The Doppler perfusion index (DPI the ratio of arterial to total liver blood flow) was measured in 46 patients aged 29-83 years, exhibiting up to four focal hyperechoic liver lesions at ultrasound examination. They comprised histopathologically proven liver metastasis of colorectal (19 cases) and gastric (10 cases) adenocarcinoma without local recurrence at the site of the previously resected primary tumour, along with 17 subjects with haemangioma. All patients underwent volumetric assessment using multislice computed tomography to calculate total volume of hepatic lesions., Results: The mean DPI of patients with colorectal (36 ± 2 %) and gastric (39 ± 6 %) metastasis was significantly higher than those with haemangioma (14 ± 2 %) (both p < 0.001), whereas metastatic groups did not exhibit any difference in terms of mean DPI. Statistically significant correlations were found between DPI values and calculated total volume of lesions in patients with colorectal and gastric metastasis (r = 0.55, p = 0.01 and r = 0.85, p = 0.002, respectively) while this correlation was not demonstrated in the haemangioma group. Simple linear regression analysis revealed that every 1 cm(3) increment in total volume of metastatic lesions increased DPI by 0.2 % [95 % confidence interval (CI) 0.1-0.3, p = 0.001]., Conclusion: Doppler perfusion index alterations are directly correlated with total volume of metastatic deposits, and DPI measurement can be a valuable method to distinguish haemangioma from hyperechoic colorectal and gastric metastatic lesions.

Background: Scientific progress is an important indicator for the social and economic developments of any country. According to various reports, worldwide, Iran has the most growth in the field of science due to a high increase in the numbers of publications during the past decade. The aim of this study is to assess not only the quantity, but also the quality of publications of indexed Iranian journals and compare them to Turkey, as an Islamic neighboring country, in addition to the contributions of these two countries to our knowledge. A number of international journals with high impact factors were selected to assess the contributions of scientists from Iran and Turkey to the medical sciences., Methods: English medical journals from Iran and Turkey indexed by the ISI Web of Sciences with known impact factors (IF) announced at the beginning of 2010 were included for evaluation. We calculated the number of all articles published from the beginning of 2007 until the October 2010, the number of total citations, and citations from authors outside both countries for each journal. In addition, we selected all articles cited at least six times by authors outside of both countries and discussed their content with regard to originality and novelty, as well as their contributions to current knowledge. Furthermore, 60 international journals in basic or clinical research with IF greater than 6 were selected for the magnitude of contributions of both countries to our scientific knowledge., Results: In 2010, out of a total of 21 Iranian journals indexed in ISI since 2007, only 12 have a known IF with a mean of 0.39 (range: 0.07-0.97), whereas out of 28 Turkish medical journals indexed in ISI, 15 have a known IF (mean: 0.35, range: 0.05-0.82). The total number of articles published since 2007 from Iran, total citations and total citations by authors from outside Iran were 2080, 1218, and 463, respectively. The same data related to Turkish journals were 4876, 2036, and 1331, respectively. Indeed, the mean citations per article by foreign authors for Iranian and Turkish researchers were 0.19 and 0.3, respectively. Of the total articles during this period, only seven from Iran and nine from Turkey have been cited at least six times by authors outside the two countries. Iran had 23 and Turkey 37 original publications in highly reputable international journals. Turkey was more represented in basic research and clinical observational studies than Iran., Conclusion: Despite high numbers of published articles, both countries have medical journals with very low comparable citation rates and IF. Only one out of three Turkish articles is cited once by authors outside of Turkey and one of five Iranian articles is cited by authors outside Iran. The few high-cited articles address new therapies and interventional studies or diseases commonly encountered regionally, and are the results of the efforts of a few individuals in highly specialized fields. Turkish scientists are inclined to publish their scientific works more than Iranians in distinguished international journals. These articles deal more with regional diseases that are not common in Western countries. Developing countries can only contribute to world science when they focus their efforts on teamwork in order to research ways to solve country-specific diseases and their own health problems.

Aim: To determine the sensitivity and specificity of endoscopic ultrasonography (EUS) in patients with inconclusive magnetic resonance imaging/magnetic resonance cholangiopancreatography (MRI/MRCP) in pancreatobiliary abnormalities., Methods: During 10 months, patients with pancreatobiliary diseases referred to endoscopic retrograde cholangiopancreatography (ERCP) because of inconclusive MRI/MRCP diagnosis were scheduled to undergo endoscopic ultrasonography. Patients were divided into four major groups: patients with (i) resectable periampullary neoplasms who were referred to a surgeon, (ii) unresectable periampullary cancer who underwent ERCP for biliary stenting, (iii) bile duct stone who were referred to ERCP for stone extraction, and (iv) normal pancreatobiliary tract. Reference standards for comparison were ERCP, surgery, a biopsy confirming malignancy, or the clinical course during follow up (at least 12 months) in cases without evidences of malignancy., Results: One hundred and seven patients (51 men; mean [SD] age 60.0 [15.5]) were included in the study. Final diagnoses were common bile duct (CBD) stone (n = 24), periampullary neoplasms (n = 46), others (n = 23) and no pathologic findings (n = 14). EUS determined the staging for clinical decision-making in 47 patients with neoplasms which showed that tumors in 34 patients (79.1%) were unresectable (advanced stage). After EUS, 47 patients (43.9%) did not require ERCP. The accuracy of EUS for the diagnosis of CBD stone and periampullary neoplasms were 96.3% and 99.1%, respectively., Conclusions: EUS is a useful modality in cases of inconclusive MRI/MRCP indicating pancreatobiliary disorders.

Iran as a developing nation is in epidemiological transition from communicable to non-communicable diseases. Although, cancer is the third cause of death in Iran, it;s mortality are on the rise during recent decades. This mini-review was carried out to provide a general viewpoint on common cancers incidence in Iran and to explain incidental differences that may help us to establish early detection programs and investigate population risk factors. A detailed PubMed, Scopus and Google scholar search were made from 2000 to 2009. The basic inclusion criteria were all relevant studies focused on cancer epidemiological data from Iran. Overall age-standard incidence rate per 100 000 population according to primary site is 110.43 in males and 98.23 in females. The five most common cancers (except skin cancer) are stomach, esophagus, colon-rectum, bladder and leukemia in males, and in females are breast, esophagus, stomach, colon-rectum and cervix uteri. The incidence rates of gastrointestinal cancers are high in Iran (it is one of the known areas with a high incidence of GI cancers). Breast cancer mainly affects Iranian women about a decade earlier than Western countries and younger cases are affected by an increasing rate of colorectal cancer in Iran, near the Western rates.

Background and Aims: To determine the time to normalization of common bile duct (CBD) diameter after endoscopic sphincterotomy and stone extraction in patients with choledocholithiasis., Methods: Patients with CBD dilation due to choledocholithiasis were enrolled. CBD diameter was measured by transabdominal ultrasonography before, and repeated after one, three, six and twelve months after endoscopic sphincterotomy and stone extraction, until normalization of CBD diameter., Results: Of 115 cases enrolled over a 36-month period, CBD diameter reversed to normal in 71 (61.7%) patients after one month. Of the remaining 44 patients, CBD diameter reversed to normal in 36 patients (including 3 in whom repeat ERCP revealed choledocholithiasis) at the end of three months. CBD diameter had not reversed to normal diameter in 8 (18.2%) patients; none of these patients had symptoms. Two of them had asymptomatic dilated CBD after 6 months with no abnormal liver function tests (LFT); the duct reversed to normal at the last follow-up (month 12)., Conclusions: Asymptomatic CBD dilation may persist in a minority of patients (18% at the end of 3 months) after removal of CBD stones. A dilated CBD can be attributed to retained choledocholithiasis within the first month, if it is associated with symptoms and abnormal LFT.

Background/aims: Endoscopic ultrasonography (EUS) is a useful modality to diagnose causes of pancreatitis. The role of EUS for prediction of pancreatitis severity has not been studied. The aim of this study was to identify the utility of EUS in determining the severity of acute pancreatitis (AP)., Methods: All patients diagnosed with pancreatitis consecutively underwent EUS on the 2nd day of their admission. Atlanta criteria were used as the severity index of pancreatitis., Results: During the study period, 114 patients (74 females, 40 males; mean age of 53.03 ± 17.7 years) were enrolled in the study. The most common cause of AP was gallstone (78.9%). According to the Atlanta criteria, pancreatitis was mild in 72 (63.2%) and severe in 42 (36.8%) patients. In univariate analysis, the presence of peripancreatic edema, pancreas inhomogeneity, common bile duct dilation and ascites were associated with severe pancreatitis. In multivariate analysis, only the presence of peripancreatic edema in EUS correlated with the severity of AP according to the Atlanta criteria (sensitivity, specificity and accuracy: 65.8, 75.7 and 72.2%, respectively)., Conclusion: EUS may be a new useful imaging modality for prediction of severity of AP and may have prognostic significance in the early phase of AP. and IAP., (Copyright © 2011 S. Karger AG, Basel.)

Background: Endoscopic retrograde cholangiopancreatography with endoscopic sphincterotomy has become widely available for the treatment of pancreatobiliary diseases; however, it has mortality and complications. The aim of this study was to compare the success rates and complications of two different methods of common bile duct cannulation., Methods: From June 2003 though February 2004, patients who were candidates for endoscopic retrograde cholangiopancreatography and/or endoscopic sphincterotomy were randomly divided into two groups: standard cannulation (group A) and suprapapillary needle-knife fistulotomy (group B). Postendoscopic retrograde cholangiopancreatography pancreatitis, cholangitis, bleeding, and perforation were evaluated., Results: Two hundred and eighteen cases (86 males and 132 females with a mean+/-SD age of 56.2+/-17.5 years) were enrolled in this study. Group A, contained 112 patients and group B included 106 patients. In group A, the final cannulation success was achieved in 100 patients (89.3%). Cannulation was successful in 88 patients (83.0%) in group B. Difficulty in cannulation occurred more frequently in group A (25.5% vs. 2.6%, P=0.002). There were two patients in group B and three patients in group A who developed pancreatitis after endoscopic retrograde cholangiopancreatography. Perforation occurred in one patient in group B, which was improved with medical support. Bleeding and cholangitis were not occurred in any of the groups. The overall complication rate was 3/112 in group A and 3/106 in group B., Conclusion: Needle-knife fistulotomy is safe and can be applied as an effective alternative to standard technique for common bile duct cannulation in expert hands.

Objective: Endoscopic ultrasonography has been accepted as a sensitive modality for preoperative tumor localization in pancreas. We have aimed to determine the performance characteristics of endoscopic ultrasonography in pancreatic insulinoma localization and evaluation of relationship between the tumor size and serum-c peptide level, lowest glucose level and insulin level., Methods: Patients suspicious to insulinoma according to clinical and laboratory findings were included. Endoscopic ultrasonography was performed and if a tumor was identified, the patient was referred for surgery., Results: A total of 52 patients (24 male and 28 female) with mean age of 42.4 years underwent EUS and 43 patients underwent surgery. In one patient, a tumor was identified both by transabdominal ultrasonography and abdominal CT scan. The overall sensitivity and accuracy of endoscopic ultrasonography for detection of insulinoma was 89.5% and 83.7% respectively. The sensitivity of endoscopic ultrasonography for detection of lesions in pancreatic head, body and tail was 92.6%, 78.9%, and 40.0%, respectively. There was no relationship between c-peptide, lowest blood glucose, insulin blood levels and tumor size in surgery., Conclusion: EUS is an accurate method for detection of insulinoma. The accuracy depends on the location of the tumor and is greatest for tumors in the pancreatic head.

Objectives: Acute pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). Many medications have been used to prevent this complication. We aimed to evaluate the efficacy of rectally administered indomethacin for the prevention of post-ERCP pancreatitis., Methods: During 18 months, all eligible patients who underwent ERCP were enrolled in this study. In a double-blind randomized trial, patients received a suppository containing indomethacin, 100 mg, or an inert placebo immediately before ERCP. Serum amylase levels and clinically pertinent evaluations were measured in all patients after ERCP., Results: A total of 490 patients entered the trial, of which half received indomethacin. Twenty-two patients developed pancreatitis; seven cases in the indomethacin group and 15 in the placebo group (P=0.06). Pancreatic duct injection (OR=3.0, 95% CI: 1.3-7.4), pancreatic duct cannulation more than once (OR=4.2, 95% CI: 1.7-10.0), and age less than 60 yr (OR=2.7, 95% CI: 1.0-7.1) were shown to be significant risk factors for developing post-ERCP pancreatitis. In patients who underwent pancreatography with or without cholangiography, the risk of pancreatitis was significantly lower in the indomethacin group compared with the control group (P=0.01, RRR=88%, ARR=0.16, NNT=6). Moderate to severe pancreatitis was significantly higher in the placebo group (P= 0.03)., Conclusions: This trial shows that rectal indomethacin given immediately before ERCP can reduce the incidence and severity of post-ERCP pancreatitis.

Objective: The purpose of this study was to evaluate the impact of substituting endoscopic ultrasonography (EUS) for endoscopic retrograde cholangiopancreatography (ERCP) in cases of a low to intermediate risk for choledocholithiasis., Methods: During a 16-month period, patients who were referred for suspected choledocholithiasis, biliary colic, or acute biliary pancreatitis on the basis of alterations in liver enzyme values with or without gallstones seen on transabdominal ultrasonography were included. Endoscopic ultrasonography was performed for all patients. Patients with common bile duct stones underwent ERCP. Cholecystectomy was recommended in all patients with symptomatic gallstones. Cases were followed for 12 months., Results: A total of 150 patients were included. Choledocholithiasis was diagnosed by EUS in 39 patients (26.0%) and was confirmed by ERCP in 30 (77.0%). Fifty-one patients had a normal common bile duct, and follow-up for 12 months showed no abnormalities except in 1 patient. Cholecystectomy without ERCP was recommended for the remaining 60 patients who had symptomatic gallstones or sludge. Endoscopic retrograde cholangiopancreatography was avoided by this approach in 110 patients (73.3%)., Conclusions: In a low to intermediate risk for choledocholithiasis, EUS can preclude the need for ERCP in most cases.