Nilesh Chande

C-Reactive Protein, Fecal Calprotectin, and Stool Lactoferrin for Detection of Endoscopic Activity in Symptomatic Inflammatory Bowel Disease Patients: A Systematic Review and Meta-Analysis.

Objectives:Persistent disease activity is associated with a poor prognosis in inflammatory bowel disease (IBD). Therefore, monitoring of patients with intent to suppress subclinical inflammation has emerged as a treatment concept. As endoscopic monitoring is invasive and resource intensive, identification of valid markers of disease activity is a priority. The objective was to evaluate the diagnostic accuracy of C-reactive protein (CRP), fecal calprotectin (FC), and stool lactoferrin (SL) for assessment of endoscopically defined disease activity in IBD.Methods:Databases were searched from inception to November 6, 2014 for relevant cohort and case-control studies that evaluated the diagnostic accuracy of CRP, FC, or SL and used endoscopy as a gold standard in patients with symptoms consistent with active IBD. Sensitivities and specificities were pooled to generate operating property estimates for each test using a bivariate diagnostic meta-analysis.Results:Nineteen studies (n=2499 patients) were eligible. The pooled sensitivity and specificity estimates for CRP, FC, and SL were 0.49 (95% confidence interval (CI) 0.34–0.64) and 0.92 (95% CI 0.72–0.96), 0.88 (95% CI 0.84–0.90) and 0.73 (95% CI 0.66–0.79), and 0.82 (95% CI 0.73–0.88) and 0.79 (95% CI 0.62–0.89), respectively. FC was more sensitive than CRP in both diseases and was more sensitive in ulcerative colitis than Crohn’s disease.Conclusions:Although CRP, FC, and SL are useful biomarkers, their value in managing individual patients must be considered in specific clinical contexts.

Interventions for Treating Microscopic Colitis: A Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Review Group Systematic Review of Randomized Trials

OBJECTIVES:To conduct a systematic review to determine effective treatments for patients with collagenous colitis or lymphocytic colitis, the two subtypes of microscopic colitis.METHODS:Relevant papers were identified via the MEDLINE, PUBMED, and Cochrane Collaboration databases, manual searches of the references of identified papers and review papers on microscopic colitis, as well as searches of abstracts from major gastroenterological meetings.RESULTS:All studies assessing treatment of microscopic colitis had relatively small sample sizes. A total of 10 randomized trials included patients with collagenous colitis. Budesonide was studied for induction of response in three trials and for maintenance of response in two trials. The pooled odds ratio for inducing clinical response with budesonide was 12.32 (95% confidence interval, CI 5.53–27.46), and for maintaining clinical response was 8.82 (95% CI 3.19–24.37), with a number needed to treat (NNT) of 2 patients for each outcome. Budesonide also induced and maintained histological response and was well tolerated. Bismuth subsalicylate, prednisolone, and mesalamine with or without cholestyramine may be effective, whereas Boswellia serrata extract and probiotics were ineffective for treating collagenous colitis. Three randomized trials included patients with lymphocytic colitis. Budesonide was shown in one study to be effective for inducing clinical response (OR 9.00; 95% CI 1.98–40.93), with an NNT of three patients. Budesonide also induced histological response and was well tolerated. Bismuth subsalicylate and mesalamine with or without cholestyramine may be effective for treating lymphocytic colitis. No trials assessed maintenance of response in patients with lymphocytic colitis.CONCLUSIONS:Budesonide is effective and well tolerated for inducing and maintaining clinical and histological responses in patients with collagenous colitis, and for inducing clinical and histological responses in patients with lymphocytic colitis. Determining the magnitude of benefit is limited by the small sample sizes of the studies. The evidence for other agents, including bismuth subsalicylate, prednisolone, B. serrata extract, probiotics, and mesalamine with or without cholestyramine is weaker. It is not clear that any of these agents induce or maintain actual remission of collagenous or lymphocytic colitis, as opposed to clinical or histological response.

Collagenous colitis and lymphocytic colitis: Patient characteristics and clinical presentation

Objective. Collagenous colitis and lymphocytic colitis (collectively known as microscopic colitis) are characterized by chronic diarrhea, normal endoscopic and radiologic findings, and typical findings on histologic examination of colonic tissue. The purpose of this study was to define the background characteristics of patients with microscopic colitis, as well as to present symptoms, coexistent autoimmune diseases, and a possible association with the use of non-steroidal anti-inflammatory drugs (NSAIDs) and ticlopidine. Material and methods. A retrospective chart review was carried out on all cases of collagenous colitis and lymphocytic colitis diagnosed at a single center from July 1992 to July 2002. Results. Of the 104 patients identified, 66 had collagenous colitis, 35 had lymphocytic colitis, and 3 were diagnosed with both disorders at different times. The mean age of patients was 64 years (26–88 years), with a female:male ratio of 4.8:1. The most common presenting symptoms were diarrhea (95%), weight loss (41%), abdominal pain (40%), fecal urgency (29%), and nocturnal stools (22%). Autoimmune disease was diagnosed in 29% of patients, 35% were using an NSAID, and 2% were using ticlopidine. Conclusions. Collagenous colitis and lymphocytic colitis occur more often in females than in males, at a wide age range, with a mean in the seventh decade. Certain symptoms are characteristic, but are not specific to these disorders. There may be an association with the presence of a coexistent autoimmune disorder and the use of drugs such as NSAIDs.

Meta‐analysis: vasoactive medications for the management of acute variceal bleeds

Vasoactive medications such as vasopressin, somatostatin and their analogues (terlipressin, vapreotide and octreotide) are commonly used for the treatment of acute variceal bleeding. However, the risks and benefits of these interventions are not well understood.

Microscopic colitis associated with lansoprazole: Report of two cases and a review of the literature

Microscopic colitis causes chronic watery diarrhea. Many cases may be induced by medications, and lansoprazole, a commonly used proton-pump inhibitor, has been associated with collagenous colitis and lymphocytic colitis, the two subtypes of microscopic colitis. Two cases of collagenous colitis associated with lansoprazole are reported, both in older female patients, who each developed profuse watery diarrhea within weeks of starting lansoprazole to treat upper digestive disorders. Colonoscopy was normal and biopsies demonstrated typical features of collagenous colitis. There was a rapid clinical improvement upon switching from lansoprazole to rabeprazole, and histological normalization on follow-up biopsies. A review of the literature showed 14 other cases of lansoprazole-related microscopic colitis. There are no reported cases of microscopic colitis associated with other proton-pump inhibitors, suggesting a pathophysiologic mechanism specific to the pharmacology of lansoprazole. Clinicians must be aware of this association when prescribing this medication; when a patient taking lansoprazole develops diarrhea, substituting an alternative proton-pump inhibitor should allow resolution of the diarrhea.

Outcomes of a 5-year follow-up of patients with sessile serrated adenomas

Abstract Objective. Sessile serrated adenomas (SSAs) are precursors to colorectal cancer (CRC). The purpose of this study is to determine the occurrence of new polyps and CRC in patients with an SSA over a 5-year follow-up interval. Methods. This study is a retrospective chart review of patients with SSAs diagnosed at colonoscopy in 2005. Abstracted information included patient demographics, colonoscopy information, and polyp characteristics. Results. During 2005, 34 SSAs and 5 mixed SSAs were identified in 33 patients. The mean patient age was 66 years and 58% were female. There was a family history of CRC in 45%, prior polyps in 33%, and previous CRC in 15%. The mean SSA size was 11 mm. SSAs were located proximal to the splenic flexure in 70%. Low-grade dysplasia was present in 3% of SSAs and 80% mixed SSAs. Synchronous adenomatous and hyperplastic polyps occurred respectively in 45% and 21%. High-grade dysplasia was present in 12% of the adenomas. Twenty-two patients underwent subsequent colonoscopies with 20 new SSAs and 1 mixed SSA identified. In SSAs low-grade dysplasia occurred in 10% and high-grade dysplasia in 5%. Low-grade dysplasia was present in the mixed SSA. Synchronous adenomatous and hyperplastic polyps occurred respectively in 45% and 37%. High-grade dysplasia was present in 10% of adenomas and CRC occurred in 1 (5%) patient. Conclusions. SSAs occurred more frequently in females and in the right colon. Dysplasia occurred in a small subset of SSAs. There was a high rate of prior and subsequent CRC in patients with SSAs.

The safety and efficacy of antitumour necrosis factor-alpha therapy for inflammatory bowel disease in patients post liver transplantation: a case series

The role of antitumour necrosis factor‐alpha (anti‐TNF) therapy for inflammatory bowel disease (IBD) among liver transplant recipients is largely unknown given the rarity of this population and the paucity of literature on the subject.

Are there any differences in the efficacy and safety of different formulations of Oral 5-ASA used for induction and maintenance of remission in ulcerative colitis? evidence from cochrane reviews.

Background:We systematically reviewed and compared the efficacy and safety of oral mesalamine formulations (sustained release, delayed release, and prodrugs) used for induction and maintenance of remission in ulcerative colitis. The main objective of this review was to determine if there are any differences in efficacy or safety among the oral 5-ASA drugs. Methods:A literature search in February 2013 identified all applicable randomized trials. Study quality was evaluated using the Cochrane risk of bias tool. The Grading of Recommendations Assessment, Development and Evaluation criteria were used to assess the overall quality of the evidence. Studies were subgrouped by common mesalamine comparators for meta-analysis. Studies were pooled for analysis if they compared equimolar doses of oral 5-ASA. Results:Seventeen studies that evaluated 2925 patients were identified. The risk of bias was low for most factors, although 1 study was single blind and 3 were open label. No difference was observed between oral 5-ASA and comparator 5-ASA formulations in the proportion of patients with clinical remission (relative risk, 0.94; 95% confidence interval, 0.86–1.02), clinical improvement (relative risk, 0.89; 95% confidence interval, 0.77–1.01), or relapse at 12 months (relative risk, 1.01; 95% confidence interval, 0.80–1.28). Subgroup analyses showed no important differences in efficacy. No significant difference was demonstrated in rates of adverse events or withdrawal due to adverse events. Conclusions:There does not seem to be any difference in efficacy or safety among the various formulations of oral 5-ASA. Oral mesalamine is an effective and safe treatment of mild-to-moderate or quiescent ulcerative colitis regardless of the chosen formulation.

The human proton-coupled folate transporter (hPCFT): modulation of intestinal expression and function by drugs

Folic acid is a vitamin essential for thymidylate and purine synthesis. The human proton-coupled folate transporter (hPCFT) has recently been identified as a pH-dependent folic acid transporter, and mutations in this transporter have been linked to hereditary folic acid malabsorption. In this study, we assessed hPCFT-mediated transport activity in vitro, intersubject variability of intestinal expression in relation to blood folates, and the relationship of proton-pump inhibitor (PPI) therapy on hPCFT expression in vivo. We created a Madin-Darby canine kidney strain II (MDCKII) cell line stably expressing hPCFT to evaluate its drug substrates and inhibitors. Intestinal pinch biopsies (duodenum, ileum, colon) were collected from patients undergoing routine endoscopy procedures, and expressed levels of hPCFT were determined by RT-PCR. When assessed using MDCKII-hPCFT cells, folic acid and methotrexate were found to be high-affinity hPCFT substrates. Sulfasalazine and pyrimethamine were noted to inhibit hPCFT activity with Ki values of 42.3 and 161.7 micromol/l, respectively. hPCFT was localized to the brush-border membrane of enterocytes with highest expression in the duodenum and reduced levels in the ileum and colon. When we assessed hPCFT expression in a subset of patients who were receiving PPI therapy, a near 50% reduction in duodenal hPCFT mRNA expression was noted. These results suggest that hPCFT transporter activity can be modulated by many drugs in clinical use, and expression of this transporter in the gastrointestinal tract is higher in the duodenum than more distal sites (duodenum > ileum > colon). Importantly, we note that PPI drug use appears to be associated with reduced hPCFT expression in vivo.

Intestinal CYP3A4 and midazolam disposition in vivo associate with VDR polymorphisms and show seasonal variation.

Vitamin D, whose levels vary seasonally with sunlight, is activated to 1α,25-dihydroxyvitamin D(3) that binds the vitamin D receptor (VDR) and transcriptionally regulates intestinal CYP3A4 expression. We genotyped VDR polymorphisms and determined their associations with intestinal CYP3A4 and with midazolam pharmacokinetics, and whether intestinal CYP3A4 levels/activity varied seasonally. The VDR BsmIG > A (rs1544410) polymorphism was significantly associated with CYP3A4 jejunal expression/activity, with CYP3A4 duodenal mRNA, and with midazolam area under the curve (AUC). Intestinal CYP3A4 expression/activity was significantly higher in biopsies with the VDR promoter polymorphisms Cdx2-3731G > A and GATA-1012A > G that increase VDR activation of target genes. Duodenal CYP3A4 mRNA was significantly higher between April and September than between October and March. Midazolam p.o. AUC and oral bioavailability trended higher October through March compared to April through September. These data suggest VDR polymorphisms are predictors of intestinal CYP3A4, and that CYP3A4 intestinal expression varies seasonally--likely related to annual changes in UV sunlight and vitamin D levels.