A Practical Index to Distinguish Backwash Ileitis From Crohn's Terminal Ileitis in MR Enterography.

BACKGROUND: Differentiating ulcerative colitis-associated "backwash" ileitis (BWI) from Crohn's terminal ileitis (CTI) is a diagnostic challenge and highly affects patient's management. This study aimed to investigate magnetic resonance enterography (MRE) features including ileocecal valve patency index (ICPI) in patients with BWI and CTI and distinguish these entities based on MRE findings. METHODS: After obtaining institutional review board approval, we reviewed 1654 MREs; 60 patients with pathologically proven BWI (n = 30) and CTI (n = 30) were enrolled. Two radiologists who were blinded to the clinical diagnosis analyzed MREs. We evaluated bowel wall thickness and enhancement pattern, ileocecal valve (ICV) diameter, and lip thickness. Ileocecal valve patency index-T and ICPI-C were calculated to normalize the ICV diameter with respect to terminal ileum (TI) and cecum, respectively. An additional group of non-BWI-UC patients (n = 30) was also included to validate indices. RESULTS: Circumferential mural thickening (90% vs 1%, P < .001) and inner-wall enhancement (P < .001) of TI were more frequent in BWI patients than CTI. Serosal irregularity (53% vs 13%, P = .002), higher mural thickness (5mm vs 3mm, P < .001), and asymmetric hyperenhancement (P < .001) of TI were more prevalent in CTI than BWI. Ileocecal valve patency and lip atrophy were significantly higher in BWI than CTI and non-BWI-UC groups (both P < .001). Ileocecal valve patency indices-C and ICPI-T indices were able to accurately distinguish BWI from CTI (area under the ROC curve [AUC], 0.864 and 0.847 for ICPI-T and ICPI-C, respectively) and non-BWI-UC (AUC, 0.777 and 0.791 for ICPI-T and ICPI-C, respectively). Ileocecal valve patency indices-T  ≥31.5% were 100% specific to distinguish BWI from CTI, but sensitivity was 63%. CONCLUSIONS: Magnetic resonance enterography features of ICV and TI can accurately differentiate BWI from CTI. Two practical indices introduced in this study showed high specificity to distinguish BWI from CTI.

The clinical significance of biliary findings in magnetic resonance enterography of patients with inflammatory bowel disease.

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.

Risk Factors Affecting 90-day Readmission of Patients with Inflammatory Bowel Disease.

BACKGROUND: The rate of hospital readmission is seen as a measure of quality and accountability. Knowing the risk factors that can be changed could reduce the cost burden on patients with inflammatory bowel disease (IBD) and the health system. METHODS: Retrospective analysis was performed on the data extracted from hospital records during a 4-year period. The study setting encompassed three referral hospitals in Tehran and the south of Iran. The primary outcome was hospital readmission of patients with IBD. The factors associated with binary and categorical dependent variables were analyzed using robust logistic regression and multinomial logistic regression, respectively. The significance level was set at P=0.05. RESULTS: 187 patients were admitted during the 4-year study period for an IBD-related reason, among whom 131 patients (70.1%) had ulcerative colitis (UC), and 56 patients (29.9%) had Crohn's disease (CD). Moreover, 29% (55) of the participants had been readmitted at least once during the study period, and seven patients with IBD had been readmitted five or more times during the study period. Corticosteroids (OR=4.55, 95% confidence interval CI: 1.65- 12.55) and chronic pain (OR=6.65, 95% CI: 1.73-25.62) were two factors associated with their readmission within 90 days. For the patients with five or more times of readmissions, Corticosteroids (RRR=5.68), chronic pain (RRR=5.05), length of hospital stay (RRR=0.69), and age (RRR=0.9) could significantly explain the hospital readmissions. CONCLUSION: About one in seven hospitalizations of patients with IBD leads to 30-day readmission. Moreover, younger patients with IBD and shorter length of hospital stay were more likely to be readmitted five or more times during the study period. The use of corticosteroids and the presence of chronic pain were predictors of 90-day readmission. More studies are needed to detect the best management plan for chronic pains.

Immunotherapeutic Effects of ß-D Mannuronic Acid on IL-4, GATA3, IL-17 and RORC Gene Expression in the PBMC of Patients with Inflammatory Bowel Diseases.

Inflammatory bowel diseases (IBD) are chronic relapsing immune-mediated disorders that result from an aberrant immunological response. IBD comprises of Crohn's disease (CD) and ulcerative colitis (UC). The precise aetiology of IBD has not been fully understood, however, recent studies support the hypothesis that patients with IBD have a dysregulated immune response to endogenous bacteria in the gastrointestinal tract (GIT). The increasing number of hospitalisation coupled with the high economic burden faced by IBD patients, calls for more concerted research efforts, to design a potent and credible treatment option for these strata of patients. This research was designed to test the efficacy and potency of ß-D Mannuronic acid (M2000) in the treatment of IBD. Ten ml of blood was aseptically collected from 24 IBD patients and 24 normal controls. PBMC was isolated and stimulated with 1 µg/mL of LPS and incubated for 4 hours. The cells were later treated with 10 µg/mL or 50 µg/mL of Mannuronic acid and incubated for 24 hours at 370C under 5% CO2 and 100% humidity. After the incubation, RNA was extracted from the cells, cDNA was synthesised, and the expression of the gene was evaluated using quantitative real-time PCR. The result indicated a significant down-regulation of RORC and IL-17 genes expression, while the expression of IL-4 and GATA3 genes were significantly up-regulated. These research findings have shown that M2000 a biocompatible agent, that has an immunotherapeutic, immunomodulatory and immunosuppressive effects on the PBMC of IBD patients.

Dietary fiber and risk of irritable bowel syndrome: a case-control study.

AIM: The purpose of this study was to determine the relationship between dietary fiber intake and risk of irritable bowel syndrome (IBS). BACKGROUND: Patients with IBS are usually concerned about their diet, which can exacerbate or relieve their symptoms. METHODS: In this case-control study, ninety cases and 355 controls were selected from a gastroenterology clinic. Dietary intakes of participants were assessed using a validated and reliable food frequency questionnaire (FFQ). Dietary fiber was calculated according to United States Department of Agriculture (USDA) food composition table. RESULTS: Dietary total fiber intake was significantly associated with lower risk of IBS. The adjusted odds ratio (OR) comparing the highest tertile of dietary total fiber with the lowest tertile was 0.14 (95% CI = 0.71-0.28; P-test for trend <0.001); however, there was no significant association or dose-response trend for higher intakes of soluble, and insoluble fiber separately with risk of IBS. CONCLUSION: Our data indicate that dietary fiber is inversely associated with the risk of IBS. Further prospective studies are needed to confirm these data.

Immunomodulatory effects of M2000 (ß-D-Mannuronic acid) on TNF-α, IL-17 and FOXP3 gene expression in patients with inflammatory bowel disease.

INTRODUCTION: Inflammatory bowel diseases (IBD) are immune-mediated disorders that result from an aberrant immunological response to the gut luminal antigen in genetically susceptible patients. IBD is categorized into two serotype, Crohn's diseases (CD) and ulcerative colitis (UC), both subtype are important cause of gastrointestinal diseases. The increasing rate of hospitalization, with the high economic burden experienced by the IBD patients, calls for more concerted research efforts to design a potent and affordable treatment option for the treatment of IBD. AIMS/OBJECTIVE: This research was designed to test the efficacy and potency of ß-D Mannuronic acid (M2000) and assess if it could serve as a better therapeutic option in the treatment of IBD. METHODOLOGY: Ten (10)ml of blood was aseptically collected into an EDTA container, from 24 IBD patients and 24 normal healthy controls. PBMC was isolated and stimulated with 1µg/ml of LPS in cell culture plate and incubated for 4h. The cells were later treated with 10µg/ml and 50µg/ml of ß-D Mannuronic acid (M2000) and incubated for 24h at 37°C under 5% CO2 and 100% humidity. The RNA extractions, cDNA synthesis, and QRT-PCR were performed. RESULTS: Our findings showed a significant down-regulation of TNF-α and IL-17 gene expression, while the expression of FOXP3 gene was significantly up-regulated. CONCLUSION: This result has indicated that ß-D Mannuronic acid (M2000) have immunoregulatory and anti-inflammatory effects on these cytokines that are pivotal in the pathogenesis of IBD.

A randomized, double blinded, placebo-controlled clinical trial of silymarin in ulcerative colitis.

OBJECTIVE: To evaluate the clinical efficacy of silymarin in ulcerative colitis (UC) patients. METHODS: A randomized double blinded placebo-controlled clinical trial was conducted in 80 UC patients whose disease had been documented and were in remission state between September 2009 and October 2010. Patients were assigned to silymarin group (42 cases) and placebo group (38 cases) using a random number table. Either silymarin (140 mg) or placebo (lactose mono-hydrate, corn starch magnesium stearate) tablets were given once daily for 6 months along with their standard therapy. The efficacies were assessed by disease activity index (DAI), frequency difference of the disease flare-up, and paraclinical data. RESULTS: Ten patients (4 in the silymarin group due to nausea and 6 in the placebo group due to disease flare-up and abdominal pain) discontinued the study. An improvement in hemoglobin level (11.8±1.6 g/dL vs. 13.4±1.2 g/dL,P<0.05) and erythrocyte sedimentation rate (23.7±11.5 mm/h vs.10.8±3.2 mm/h,P<0.05) was observed in the silymarin group but not in the placebo group. DAI significantly decreased in the silymarin group and reached from 11.3±3.5 to 10.7±2.8 (P<0.05). Thirty-five out of 38 patients in the silymarin group were in complete remission with no flare-up after 6 months as compared to 21 out of 32 patients in the placebo group (P=0.5000). CONCLUSION: Silymarin as a natural supplement may be used in UC patients to maintain remission.

Screening colonoscopy in first-degree relatives of patients with colorectal cancer.

BACKGROUND: Colorectal cancer (CRC), one of the most important causes of morbidity and mortality, has earned the attention of healthcare systems widely. Screening programs are designed to detect patients at risk as effectively as possible. One of the major CRC risk factors is having a family member with diagnosed CRC. AIM: To investigate the association between presence of polyps on colonoscopy and family history of CRC. METHODS: This was a retrospective cohort study in which the data was collected from colonoscopy reports of patients with/without familial history of CRC in Masoud private clinic, Tehran, Iran from October 1, 2011 to October 1, 2012. The association between presence of colorectal polyps on colonoscopy and family history of CRC was then assessed. RESULTS: A total of 210 patients were included in the study, constituting two groups with/without familial history of CRC with a 1:1 ratio (105 subjects in each group). Compared to subjects with a negative family history of CRC, a 2.7-fold (CI 95%: 1.2-6.24) fold increase was observed in those with a positive family history to have colorectal polyps. In multivariate regression analysis, family history of CRC was the only independent variable associated with presence of colorectal polyps (odds ratio: 3.12, CI 95%:1.22-8). CONCLUSION: A positive family history of CRC is a risk factor for colorectal polyps.

The trend of national and sub-national burden of gastrointestinal and liver diseases in Iran 1990 to 2013; study protocol.

BACKGROUND: It is expected that gastrointestinal (GI) and liver diseases inflict considerable burden on health systems in Iran; therefore, highlighting the significance of GI disorders across the other most burdensome diseases requires comprehensive assessment and regular updates of the statistics of such diseases in Iran. OBJECTIVE: To assess in-depth sub-national estimates and trends for the incidence and prevalence of selected GI and liver diseases by age, gender and province over the period 1990 - 2013 in Iran. METHODS: This is a national and sub-national burden of disease study on 21 GI diseases using all available data sources, including cancer registry, death registration system data, hospital data, and all available published data. Analyses will be performed separately by gender, age groups, year, and province. We will conduct 21 separated systematic reviews of the literature for 21 diseases categories through searching online international electronic databases (i.e. the Medline database of the National Library of Medicine, Web of Science, and Scopus), Iranian search engines (i.e., IranMedex, Scientific Information Database (SID), and IRANDOC), and gray literature. We will search the medical literature published between January 1985 and December 2013. We generated two models, Spatio-temporal and Multilevel Autoregressive models, to estimate mean and uncertainty interval for the parameters of interest by gender, age, year, and province. The models will be informed by data of gender, age, year, and province. Markov Chain Monte Carlo (MCMC) methods will be used to perform Bayesian inference in both modeling framework. All programs will be written in R statistical packages (version 3.0.1). RESULTS: We will calculate and present 1990 to 2013 trends in terms of prevalence, years of life lost due to premature mortality (YLLs), years lived with disability (YLDs), and disability-adjusted life years DALYs for the 21 selected GI diseases by gender, and province. We will also quantify the uncertainty interval for the estimates of interest. CONCLUSION: Results of the present study will have implications for policy making; as they allow for understanding geographic distributions of the selected GI diseases, and identifying health disparities across provinces.

Three common CARD15 mutations are not responsible for the pathogenesis of Crohn's disease in Iranians.

BACKGROUND/AIMS: Crohn's disease frequency has increased in recent years in Iran. Genetic and environmental factors predispose people to this disease. Mutation in Caspase Recruitment Domain 15 (CARD15) gene is the most well known genetic predisposing factor to this disease. Frequency of three common CARD15 mutations has been studied in different ethnic groups. We aimed to study the frequency of these mutations in Iranian patients affected with Crohn's Disease. METHODOLOGY: One hundred fifteen proved cases of Crohn Disease and 115 age and sex matched normal controls were recruited in this study. Lf1007fs, R702W and G908R mutations were studied by Polymerase Chain Reaction-Restriction Fragment Length Polymorphims (PCR-RFLP) followed by sequencing the positive cases. RESULTS: Lf1007fs and G908R mutations were not found in either patients or age-sex matched controls. Just in two patients, R702W mutation was proved by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) and sequencing. None of these patients had illeal or fibrostenotic type of disease while 14.7% of total patients had stricturing type of disease. No complication was seen in these two patients while 50.4% of patients had acquired complications during the course of disease. CONCLUSION: The three mutations described are not responsible for the pathogenesis of Crohn's Disease in Iranians. The results are in accordance with other Asian nations' studies on IBD Patients.

Comparison of colonic transit time between patients with constipation-predominant irritable bowel syndrome and functional constipation.

BACKGROUND/AIM: Functional constipation (FC) and constipation-predominant IBS (C-IBS) are two main subtypes of constipation. Using radio-opaque markers is an easy and cost effective method to measure colonic transit time (CTT). We designed this study to compare the CTT between these two groups of constipated patients. METHODS: Patients with chronic constipation of no organic etiology were classified as having FC or C-IBS according to the Rome II criteria. All patients ingested 10 radio opaque markers daily for six days. A plain abdominal X-ray was taken on the seventh day. To calculate the total and segmental colonic transit time in hours, number of markers in right and left colonic and rectosigmoid area were counted and multiplied by 2.4. The mean total and segmental colonic transit time were compared between the two groups. RESULTS: A total of 100 patients (50 FC and 50 C-IBS) were enrolled. The mean (SD) total CTT was not significantly different between FC patients (52.2 [35.5] h) and C-IBS patients (41.2 [31.6] h; p = 0.10). The mean rectosigmoid transit time was significantly slower in FC patients (19.9 [15.5] h) compared to C-IBS patients (11.9 [10.6] h; p = 0.003). CONCLUSION: Rectosigmoid transit time in FC patients is slower than in C-IBS patients.

A case-control study on risk factors of osteoporosisin patients with Crohn's disease.

BACKGROUND: Osteoporosis has been frequently reported in patients with inflammatory bowel diseases, especially Crohn's disease. METHODS: All consecutive Crohn's disease patients who attended the GI Clinics at Shariati Hospital, Tehran, Iran, from 2004 to 2007 were evaluated. A BMD-DEXA assessment was performed for all patients. Among those patients diagnosed with osteoporosis (T score

Epidemiologic characteristics of 500 patients with inflammatory bowel disease in Iran studied from 2004 through 2007.

BACKGROUND: Despite claims of rarity, some studies indicate that the prevalence of inflammatory bowel disease has increased in Iran during the past decades. Establishment of a registry and the clinical characteristics are presented in this study. METHODS: Two hundred ninety-three patients with ulcerative colitis and 207 with Crohn's disease, referred to tertiary referral gastrointestinal centers in Tehran from 2004 through 2007, were assessed. Demographic and clinical features, intestinal and extraintestinal manifestations, inflammatory bowel disease in relatives, measles infection and vaccination, nutrition during infancy, and drugs and surgical interventions were assessed. RESULTS: The mean+/-SD age at the diagnosis was 33.8+/-12.9 years in Crohn's disease and 37.1+/-13.7 years in ulcerative colitis. Male:female ratio was 0.9:1.0 for Crohn's disease and 0.7:1.0 for ulcerative colitis. A total of 177 (85.5%) patients with Crohn's disease, and 254 (86.7%) patients with ulcerative colitis had never smoked. Measles vaccination was mentioned in 150 (72.5%) of Crohn's disease and 214 (73%) of ulcerative colitis patients. Breastfeeding during infancy was reported in 178 (86%) and 257 (87.7%) of Crohn's disease and ulcerative colitis patients, respectively. Appendectomy was reported in 37 (17.9%) of Crohn's disease and 16 (5.5%) of ulcerative colitis patients, whereas tonsillectomy was reported in 11.6% of each group. CONCLUSION: Demographic and clinical characteristics of inflammatory bowel disease patients are similar to that of other developing countries, in this study, more inflammatory bowel disease cases have been assessed in comparison with previous studies, which may be due to different time scales of socioeconomic evolution and environmental factors in Iran.