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Background Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Using a novel electronic reporting tool, we aimed to prospectively describe the onset of tofacitinib efficacy during induction therapy in a real-world study. Methods Patient-reported outcome data (PROs) including the simple clinical colitis activity index (SCCAI), PRO Measurement Identification Systems (PROMIS) measures, and adverse events were collected daily for the first 14 days and at day 28 and 56. Paired t tests and P for trend were utilized to compare changes in SCCAI over time. Bivariate analyses and logistic regression models were performed to describe response (SCCAI Results Of all included patients (n = 96), 67% had failed ≥2 biologics, and 61.5% were on concomitant steroids. Starting at day 3, PROs showed significant and persistent decline of the mean SCCAI (−1.1, P < 000.1) including significantly lower SCCAI subscores for stool frequency (−0.3; P < .003), bleeding (−0.3; P < .0002) and urgency (−0.2; P < .001). Steroid-free remission at day 14, 28, and 56 was achieved in 25%, 30.2%, and 29.2% of patients, respectively. Neither prior biologics nor endoscopic severity were independently predictive of response or remission in multivariate models. Numeric improvements in all PROMIS measures (anxiety, depression, social satisfaction) were seen through day 56. Rates of discontinuation due to adverse events were low. Conclusions In this prospective real-world study, tofacitinib resulted in a rapid and persistent improvement in UC disease activity PROs. The safety findings were consistent with the established safety profile of tofacitinib.

Background Several studies determined that autoimmune hemolytic anemia (AIHA) is a rare extraintestinal IBD manifestation, related to the underlying disease activity. However, evidence linking biologic therapy to AIHA is sparse. Methods This article reviews the evidence on the association of these clinical phenomena. Results There are two retrospective studies and a few case reports linking biologic therapies to AIHA. Conclusions While some autoimmune phenomenon triggered by our biologic therapies have been well recognized, we do not find the evidence associating these therapies to AIHA sufficiently compelling.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gut. Available drugs aim to suppress gut inflammation. These drugs have significantly delayed disease progression and improved patients’ quality of life. However, the disease continues to progress, underscoring the need to develop novel therapies. Aside from chronic gut inflammation, IBD patients also experience a leaky gut problem due to damage to the intestinal epithelial layer. In this regard, epithelial regeneration and repair are mediated by intestinal stem cells. However, no therapies are available to directly enhance the intestinal stem cells’ regenerative and repair function. Recently, it was shown that active vitamin D, i.e., 1,25-dihydroxyvitamin D or 1,25(OH)2D, was necessary to maintain Lgr5+ intestinal stem cells, actively cycling under physiological conditions. In this study, we used two strategies to investigate the role of 1,25(OH)2D in intestinal stem cells’ regenerative function. First, to avoid the side effects of systemic high 1,25(OH)2D conditions, we used our recently developed novel strategy to deliver locally high 1,25(OH)2D concentrations specifically to inflamed intestines. Second, because of the Lgr5+ intestinal stem cells’ active cycling status, we used a pulse-and-chase strategy via 5-bromo-2′-deoxyuridine (BrdU) labeling to trace the Lgr5+ stem cells through the whole epithelial regeneration process. Our data showed that locally high 1,25(OH)2D concentrations enhanced intestinal stem cell migration. Additionally, the migrated cells differentiated into mature epithelial cells. Our data, therefore, suggest that local delivery of high 1,25(OH)2D concentrations is a promising strategy to augment intestinal epithelial repair in IBD patients.

Helicobacterpylori (H. pylori) is a Gram-negative bacterium that colonizes gastric mucosa and is often transmitted through direct contact with saliva, contaminated food or water, and vomit. The majority of the infected individuals remain asymptomatic for a long period. Infection with H. Pylori often presents with dyspepsia, nausea, frequent belching, bloating, abdominal discomfort, burning abdominal pain, and peptic ulcer. A potential association between H. Pylori and recurrent aphthous stomatitis was previously reported; however, the presence of causative relationship between the two remained controversial. We are presenting a case of recurrent aphthous stomatitis of twenty-four-year history resolved after H. pylori treatment.

This research aims at investigating the motivational factors of university students towards English Language learning. A quantitative method using a descriptive design was recommended for this study. A questionnaire was used as the data collection tool. The population comprises all males and females third year English language learner at colleges of education and languages at Sudan University of Science and Technology. Thus, the researcher used a sample size of 100 English language learners at colleges of Education and languages in Sudan University of Science and Technology being selected as participants in the current study, 99 valid responses were collected. Collected data is entered and treated by using the Statistical Package for Social Sciences (SPSS) version 20. The following are some of important findings based on data analysis and discussion of the collected data: 1. There are many factors that have positive effect on students' attitudes and motivation to learn English language. The most important ones include, having a good English language teacher positively affects their attitudes to learn English, and Learning English is important, as it is one of the requirements for high- education.2. Students were highly motivated to learn English language. There are many factors, motivates the students, on the top of the motivates factors is that, the need for travelling around the world, and the second motivator is that, almost students confirm that, learning English makes them more knowledgeable as they can be able to communicate. Finally, the results of the study, do not detect any statistically significant variations between students of the current study perceptions regarding learning English language related to students’ gender and age.

With the early success of their trials for the treatment of ulcerative colitis, corticosteroids gained popularity as a treatment for inflammatory bowel disease (IBD). However, when used chronically, corticosteroids are not effective in maintaining remission and associated with toxic effects. Steroid-free remission has become a major treatment goal. Prolonged corticosteroid use is currently a sign of suboptimal quality of care. Trends over the past 2 decades, spanning the emergence of biologic therapies for IBD, are explored here in the University of Manitoba IBD Epidemiologic Database.

BACKGROUND Inflammatory bowel disease (IBD) patients with persistent symptoms despite no or minimal inflammation are frequently described as having an overlap of IBD and irritable bowel syndrome (IBD-IBS). Limited data are available on how IBS impacts the individual patient with IBD. In this study, we aimed to evaluate the prevalence of IBD-IBS and investigate its impact on patient-reported outcomes. METHOD We performed a cross-sectional analysis within the CCFA Partners Study. Bivariate analyses and logistic regression models were used to investigate associations between IBD-IBS and various demographic, disease factors, and patient-reported outcomes including anxiety, depression, sleep disturbances, pain interference, and social satisfaction. RESULTS Of the 6309 participants included, a total of 1279 (20%) reported a coexisting IBS diagnosis. The prevalence of IBD-IBS in this cohort was similar within disease subtypes. A diagnosis of IBD-IBS was associated with higher narcotic use compared with those with no IBS diagnosis for both Crohn's disease, 17% versus 11% (P < 0.001) and ulcerative colitis/indeterminate colitis, 9% versus 5% (P < 0.001). Quality of life, as measured by Short Inflammatory Bowel Disease Questionnaire (SIBDQ) was lower in patients with IBD-IBS compared with those without. IBD-IBS diagnosis was associated with anxiety, depression, fatigue, sleep disturbances, pain interference, and decreased social satisfaction. CONCLUSIONS In this sample of patients with IBD, high prevalence of concomitant IBS diagnosis was observed. IBD-IBS diagnosis was associated with increased narcotic use and adverse patient-reported outcome. Appropriate diagnosis, treatment, and counseling may help improve the functional status of IBD-IBS patients and decrease narcotic use.

Surveillance endoscopy of non-dysplastic Barrett's esophagus (NDBE) that fails to detect intestinal metaplasia (IM), or negative surveillance, is known to occur in clinical practice, although the frequency and possible outcomes in a large cohort in clinical practice is not well described. The goals of this study were to define frequency in which negative surveillance occurs and endoscopic outcomes in a screening cohort of short segment NDBE. A retrospective cohort (n = 184) of patients newly diagnosed with short segment NDBE at an outpatient academic tertiary care center between 2003 and 2011 were reviewed. Only those with one or more surveillance endoscopies were included to define a frequency of negative surveillance. Included patients were further assessed if they had two or more surveillance endoscopies and were classified into groups as sampling error or negative IM on consecutive surveillances based on the results of their surveillance endoscopies. The frequency of a negative surveillance endoscopy in all short-segment NDBE patients was 19.66% (92 endoscopic exams were negative for IM of 468 total surveillance exams). A negative surveillance endoscopy occurred in 40.76% (n = 75) patients. Sampling error occurred in 44.12% and negative IM on consecutive surveillance endoscopies in 55.88% of those with ≥ 2 surveillance endoscopies and an initially negative surveillance exam. The frequency of negative IM on consecutive surveillances was 19.00% of all patients who had two surveillance endoscopies. When the index diagnostic Barrett's esophagus segment length was < 1 cm, 32.14% (18/56) of all patients (with ≥ 2 surveillance endoscopies) had negative IM on consecutive surveillance endoscopies. Negative surveillance occurs frequently in short-segment NDBE. When an initial negative surveillance endoscopy occurs, it may be due to either a sampling error or lack of detectable IM on surveillance exam. When a

Budesonide is a synthetic corticosteroid characterized by enhanced topical potency and limited systemic bioavailability. Its use in ulcerative colitis (UC) was limited to rectal preparations until recently when the new oral budesonide formulation incorporating the multi-matrix system technology was introduced. The purpose of this review is to evaluate the current role of oral and rectal budesonide in managing UC patients Areas covered: In this paper, we described the chemical structure and pharmacologic characteristics of the different oral and rectal budesonide preparations, provided a summary of the published trials that evaluated the efficacy and safety of budesonide in UC, and discussed the current status of its use in this population Expert opinion: Budesonide is effective in inducing remission in a subset of patients with mild-moderate UC. Nevertheless, the current evidence suggests inferiority of oral budesonide to 5-aminosalisylates (5-ASA) and systemic steroids, whereas rectal applications are comparable to other rectal steroid preparations, but still inferior to rectal 5-ASA. In clinical practice, several issues need clarification including, its exact position in the line of induction agents; the role of combining budesonide and 5-ASAs; the role of combining oral and rectal budesonide; and the role of budesonide in maintenance therapy.

Summary Current guidelines for endoscopic surveillance of Barrett's esophagus (BE) recommend that patients with newly diagnosed BE undergo confirmatory esophagogastroduodenoscopy (EGD) to exclude the presence of dysplasia. The extent to which confirmatory endoscopy alters management and detects missed dysplasia in newly diagnosed BE has not been reported. The frequency with which confirmatory endoscopy changed surveillance management in patients with newly diagnosed BE was assessed. A two center cohort analysis was conducted on patients newly diagnosed with BE. The rate of dysplasia on confirmatory endoscopy for patients who had nondysplastic BE was obtained. Demographic and endoscopic variables were assessed for association with dysplasia detection using Firth logistic regression model. Out of the 146 patients newly diagnosed with BE and initially determined to be without dysplasia, 12 had dysplasia on the confirmatory second EGD (8.2%). Eleven of 12 cases with dysplasia on confirmatory endoscopy had long-segment BE (LSBE). Among all the LSBE cases in our cohort, 11 had newly diagnosed dysplasia on confirmatory EGD, 29.7% (11/37). The average number of biopsies obtained from the 11 LSBE cases with dysplasia was comparable with the rest of the LSBE cases without dysplasia (6.73 and 5.42, respectively, P-value 0.205). The rate of dysplasia detection in short-segment BE (SSBE) was much lower, 0.95% (1 out of 105). There were no cases of high-grade dysplasia (HGD) or cancer detected in any SSBE case. HGD was detected on confirmatory EGD in two cases, both were LSBE. Segment length was the only statistically significant factor to predict the presence of dysplasia on confirmatory endoscopy (odds ratio 9.158, P. 0.008). Confirmatory EGD in newly diagnosed LSBE had significant rate of dysplasia detection (29.7%) in this cohort. Among patients with SSBE, there was a low rate of dysplasia detection with confirmatory EGD, less than 1% of cases. No additional cases of HGD or esophageal carcinoma in SSBE cases were detected. This suggests that the yield of confirmatory EGD is greater in patients with LSBE.

Bleeding from duodenal varices is reported to be a catastrophic and often fatal event. Most of the cases in the literature involve patients with underlying cirrhosis. However, approximately one quarter of duodenal variceal bleeds is caused by extrahepatic portal hypertension and they represent a unique population given their lack of liver dysfunction. The authors present a case where a 61-year-old male with history of remote crush injury presented with bright red blood per rectum and was found to have bleeding from massive duodenal varices. Injection sclerotherapy with ethanolamine was performed and the patient experienced a favorable outcome with near resolution of his varices on endoscopic follow-up. The authors conclude that sclerotherapy is a reasonable first line therapy and review the literature surrounding the treatment of duodenal varices secondary to extrahepatic portal hypertension.

Adenosquamous carcinoma is a rare form of colorectal cancer. It is believed to be more aggressive and carries a poorer prognosis compared to the more typical colonic adenocarcinomas. Here we describe a case of primary cecaladenosquamous carcinoma invading into the terminal ileum along with a review of the literature.

Posttranscriptional gene silencing or RNA interference is a mechanism by which the expression of one or more genes is partially or fully suppressed by noncoding RNAs, particularly small RNAs. In the laboratory this concept has been utilized to introduce synthetic anti-microRNA (miRNA) oligonucleotides to downregulate or completely abrogate gene expression. MiRNAs are a group of small (~22 nucleotide), noncoding RNAs that confer such posttranscriptional regulation of gene expression.1 They have emerged as key regulators of a wide variety of biological processes and also as candidate therapeutic targets. MiRNAs silence genes by binding to target sites found within the 3′untranslated region (UTR) of the targeted mitochondrial RNA. This results in the suppression of protein synthesis and/or degradation of the transcript. A number of miRNAs have already been identified as regulators of pathways that underlie the pathogenesis of Crohn's Disease (CD).2 For example, miR-192, miR-122, miR-29, and miR-146a have been shown to target and repress NOD2, which has been implicated in CD.3, 4, 5, 6 Using small RNA-sequencing a suite of miRNAs were identified in colon tissue that stratify CD patients according to disease behavior independent of the effect of inflammation. Furthermore, levels of specific miRNAs in these patients could predict progression to penetrating and fistulizing CD.7 The purpose of this short review is to highlight the advances in using posttranscriptional gene silencing in understanding and treating CD.8, 9

Introduction: Advances in cross sectional imaging techniques have resulted in increased detection rates of indeterminate lung lesions (ILLs) during preoperative colorectal cancer staging. However detection of ILLs may result in diagnostic uncertainty, lead to unnecessary investigations with increased radiation exposure, or alter surgical or medical treatment plans. The aims of this study were to: (i.) identify the incidence of ILLs in a large cohort of patients diagnosed with colorectal adenocarcinoma; and, (ii.) evaluate the significance of these lesions. Method: A review was undertaken of consecutive patients with biopsy proven adenocarcinoma of the colon or rectum in one district general hospital over a five-year period (2002 2007; n=680). For all patients the following data were collected: number and size of lung lesions identified on preoperative thorax CT, findings of interval CT imaging, pathological staging, and disease status at final follow-up. Results: 102 (15%) of the 680 patients identified were found to have ILLs on initial preoperative CT thorax. In 44/102 cases, a solitary nodule was detected, while 35/102 had ≥ 5 nodules. 52/102 did not undergo interval evaluation of ILLs (35 had associated extra-colonic / pulmonary disease [stage 4 29; stage 3 6]). In contrast, 50/102 patients found to have ILLs on initial preoperative staging underwent interval assessment. For 20 patients, interval CT thorax (40%) demonstrated no change, in the remaining cases 17 (34%) patients were found to have decreased and 13 (26%) increased size/number of ILLs, respectively. 11/13 patients with increased ILL size / number developed pulmonary metastases (pathological stage 4 9; stage 3 1; stage 2 1). Of the 11 patients who developed lung metastases, 8 had 2 ≥ nodules at initial presentation, while bilateral ILLs were present in 6 cases. Conclusion. This study has demonstrated that ILLs can be detected by preoperative staging investigations for up to 15% of patients presenting with colorectal cancer. Progression of these lesions to recognized pulmonary metastasis was found to be associated with the presence of multiple / bilateral nodules and with the presence of nodal / distant metastases. We therefore recommend targeted surveillance in this highrisk group.