Greg Rosenfeld

Clinical Utility of Fecal Biomarkers for the Diagnosis and Management of Inflammatory Bowel Disease

Abstract:Diagnosis and monitoring of inflammatory bowel diseases rely on clinical, endoscopic, and radiologic parameters. Inflammatory biomarkers have been investigated as a surrogate marker for endoscopic diagnosis of inflammatory activity. Fecal inflammatory biomarkers such as calprotectin and lactoferrin are direct products of bowel inflammation and provide an accurate and noninvasive diagnostic and monitoring modality for Crohns disease and ulcerative colitis. This report contains an overview of the currently existing literature pertaining to clinical implications of fecal biomarkers for diagnosis, monitoring, and prediction of outcomes of inflammatory bowel disease.

The risks of post-operative complications following pre-operative infliximab therapy for Crohn's disease in patients undergoing abdominal surgery: A systematic review and meta-analysis

BACKGROUND Infliximab is an anti-TNF alpha blocker frequently utilized in the management of moderate to severe Crohns Disease. The immunosuppressive effects of infliximab may increase the risk for post-operative complications among Crohns Disease patients undergoing abdominal surgery. We conducted a systematic review and meta-analysis of studies comparing the rates of post-operative complications among Crohns disease patients treated with Infliximab therapy versus alternative therapies. METHODS We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and searched 4 electronic databases along with major conference abstract databases from inception of database until November, 2012. English-language articles and abstracts evaluating post-operative complications among Crohns disease patients were considered eligible. We applied meta-analysis with random effects model to calculate the overall odds ratio for total major complications as well as several secondary outcomes. RESULTS Data were extracted from six studies including 1159 patients among whom 413 complications were identified. The most common complications were wound infections, anastomotic leak and sepsis. There was no significant difference in the major complication rate (OR=1.59[95% CI: 0.89-2.86]; p=0.15), minor complication rate (OR=1.80 [CI: 0.87-3.71]; p=0.11), reoperation rate (OR=1.33 [CI: 0.55-3.20]; p=0.52) or 30 day mortality rate (OR=3.74 [CI: 0.56-25.16]; p=0.13) between the Infliximab and control groups. CONCLUSIONS This meta analysis provides some evidence that infliximab may be safe to continue in the pre-operative period without increasing the risk of post-operative complications for Crohns disease patients undergoing abdominal surgery.

The impact of patient education on the quality of inpatient bowel preparation for colonoscopy

BACKGROUND For patients requiring colonoscopy while admitted to hospital, achieving adequate cleansing of the colon is often difficult. OBJECTIVES To assess the impact of patient education, in the form of both counselling and written instructions, on bowel cleanliness at colonoscopy. METHODS A total of 38 inpatients at a tertiary care hospital in Vancouver, British Columbia, who were referred to the gastroenterology service for colonoscopy were enrolled in the present study. Sixteen patients were randomly assigned to the intervention group, while 22 patients comprised the control group. Both groups received a clear liquid diet and 4 L of a commercially available bowel preparation. The intervention group also received a brief counselling session and written instructions outlining the methods and rationale for bowel preparation before colonoscopy. Bowel cleanliness was assessed by the endoscopist using a five-point rating scale. RESULTS The two groups were similar with respect to demographics, the indication for colonoscopy and findings at colonoscopy. The median bowel cleanliness scores in the control group and the enhanced-instruction group were 3.0 and 2.0, respectively (P=0.001). CONCLUSION Patient counselling and written instructions are inexpensive, safe and simple interventions. Such interventions are an effective means of optimizing colonoscopy preparation in the inpatient setting.

Mycobacterium avium paratuberculosis and the etiology of Crohn's disease: a review of the controversy from the clinician's perspective.

Mycobacterium avium paratuberculosis (MAP) is an obligate intracellular organism that has frequently been associated with Crohns disease (CD). Because CD is a chronic inflammatory condition, many researchers have speculated that an infectious agent must be the cause of CD. MAP has often been proposed to be one such agent; however, despite considerable research, the evidence remains inconclusive. Higher levels of MAP have been found in the tissues and blood of CD patients than in controls, forming the foundation for much of the research into the role of MAP in CD and the primary argument in support of a causative role for MAP in CD. MAP is a slow-growing and fastidious organism that is difficult to grow in culture and, therefore, challenging to detect in patients. As a result, there has been variability in the results of studies attempting to detect the presence of MAP in CD patients, and considerable controversy over whether this organism has a causative role in the etiology of CD. Two main hypotheses exist with respect to the role of MAP in CD. The first is that MAP is a principal cause of CD, while the second is that MAP is more prevalent because of the immune dysfunction seen in CD but does not play a causative role. Clinicians are often faced with questions regarding the role of this organism and the need to treat it. The present article attempts to provide an overview of the controversy including the nature of the mycobacterium, the difficulty in detecting it, the use of antimycobacterial agents to treat it and the effect of immunosuppressive agents - all from a clinicians perspective. Although the role of MAP in CD remains controversial and an area of considerable research, it is currently only of academic interest because there is no clinically useful test to identify the presence of the organism, and no evidence to support the use of antibiotics to eradicate it for the treatment of CD.

The Impact of Dietary Interventions on the Symptoms of Inflammatory Bowel Disease: A Systematic Review

Diet may be a successful part of the treatment plan for improving outcome in patients with inflammatory bowel disease (IBD). This study aimed to systematically review all published clinical trials evaluating the effects of a regular diet on symptoms of IBD. Three medical databases were searched for clinical trials evaluating an intervention that involved dietary manipulation using a regular diet on adults with IBD whose symptoms were objectively measured before and after the intervention. The most common types of regular diet interventions that we observed in the literature fell into the following three categories: low residue/low fiber diets, exclusion diets, or other specific diets. Of all included studies, the few that were of higher quality and that observed a statistically significant improvement in symptoms in the diet group compared to the control group fell under the exclusion diet group or the other specific diet group. We were able to identify several high quality clinical trials evaluating dietary manipulations on symptoms of IBD. Exclusion diets and the low FODMAP diet are two areas identified in this review that show promise for having therapeutic benefits for patients with IBD.

Medical Imaging in Small Bowel Crohn's Disease-Computer Tomography Enterography, Magnetic Resonance Enterography, and Ultrasound: "Which One Is the Best for What?".

Background:Small bowel imaging in Crohns disease (CD) is an important adjunct to endoscopy for the diagnosis, assessment of postoperative recurrence, and detection of complications. The best imaging modality for such indications though remains unclear. This systematic review aims to identify the imaging modality of choice considering the use of ultrasound (US), computed tomography enterography (CTE), and magnetic resonance enterography (MRE). Methods:Databases were systematically searched for studies pertaining to the performance of US, CTE, and MRE, as compared with a predefined reference standard in the assessment of small bowel CD. Results:Thirty-three studies, from a total of 1427 studies, were included in the final analysis. A comparable performance was demonstrated for MRE, CTE, and US for the diagnosis of small CD. Ultrasound was found to have the highest accuracy in the differentiation of inflammation and fibrosis. Postoperative recurrence detection was feasible with the use of MRE and US. All 3 modalities were shown to have a role in the detection of small bowel CD complications. The radiation exposure associated with CTE can be minimized by using lower radiation protocols. Conclusions:Ultrasound, CTE, and MRE all play an important role in the diagnosis and management of small bowel CD, with preference for a particular modality being influenced by specific indication, institution resources, and patient preference.

Editorial: The Truth About Cigarette Smoking and the Risk of Inflammatory Bowel Disease

Abstract: The etiology of inflammatory bowel disease (IBD) is generally believed to be multifactorial in nature involving both genetic and environmental factors. Cigarette smoking has been shown through previous retrospective observational studies to be an environmental factor with both positive and negative influences in IBD. Smoking increases the risk of developing Crohns disease (CD) but not the risk of ulcerative colitis (UC). Meanwhile smoking cessation increases the risk of a UC flare while CD patients are more likely to show a decrease in disease severity. Unfortunately, these observational studies cannot control for bias the way a randomized controlled trial can, however, they still reveal meaningful truths about smoking and IBD. The study by Higuchi et al. (1) adds to our understanding of the impact of smoking on IBD in several ways. They showed that increasing exposure to smoking is associated with an increased risk of developing CD. They also showed that the risk of UC is highest in the first 2–5 years after smoking cessation but remains elevated for >20 years. This research also raises several new issues regarding the association between smoking and IBD, which hopefully will be answered through future well-designed observational studies.

Argon photocoagulation in the treatment of gastric antral vascular ectasia and radiation proctitis

Gastric antral vascular ectasia (GAVE) and radiation proctitis are two vascular disorders of the gastrointestinal tract that typically present with recurrent gastrointestinal bleeding. Although the pathogenesis of either condition is not known, they are unlikely to be similar. GAVE appears to be related to autoimmune disorders or cirrhosis, while radiation proctitis is the result of pelvic irradiation, most commonly used for the treatment of pelvic malignancies. Medical therapies for both conditions are not typically effective, and surgical therapies are usually not required because endoscopic treatment, aimed at coagulation of the underlying vascular lesions, has evolved as the most effective therapy. There is limited evidence in the literature for the use of medical and surgical therapies, with most of the evidence coming from case reports involving small numbers of patients. In the present article, we review the evidence for the use of argon plasma photocoagulation (APC, the most commonly used endoscopic modality) in the treatment of GAVE and radiation proctitis.

Treatment of Crohn's disease patients with infliximab is detrimental for the survival of Mycobacterium avium ssp. paratuberculosis within macrophages and shows a remarkable decrease in the immunogenicity of mycobacterial proteins

Dear Sir, The association between Mycobacterium avium ssp. paratuberculosis (MAP) and Crohns disease (CD) although debatable, is supported by several studies1 which have reported the detection or isolation of MAP from human tissues2 including serum,3 body fluids (breast milk),4 and high levels of TNF-α was found secreted by the gut mucosa in MAP-associated CD patients.5 Infliximab is a monoclonal antibody that specifically inhibits TNF-α and is used as a current therapy for CD. Recently, Nakase et al.6 demonstrated that THP-1 cells infected with MAP induced the production of a higher amount of TNF-α when compared to macrophages infected with either Mycobacterium avium or Mycobacterium smegmatis , suggesting that MAP is directly involved in the upregulation of this cytokine. Previously, we have reported that MAP is able to infect, reside, and multiply intracellularly in human macrophages,7,8 suggesting that the pathogen is able to subvert the hosts immune response to avoid its own demise even at the earliest stage of the infection. Moreover, we have reported that CD patients,8 but not …

Prevalence of Anxiety and Depression in Patients with Inflammatory Bowel Disease

Background Inflammatory bowel disease (IBD) patients are not routinely screened for depression and anxiety despite knowledge of an increased prevalence in people with chronic disease and negative effects on quality of life. Methods Prevalence of anxiety and depression was assessed in IBD outpatients through retrospective chart review. The presence of anxiety and/or depression was determined using the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7 self-report questionnaires or by diagnosis through psychiatric interview. Patient demographics, disease characteristics, and medication information were also collected. Multivariable analysis was used to determine associations between patient factors and depression and anxiety. Results 327 patient charts were reviewed. Rates of depression and anxiety were found to be 25.8% and 21.2%, with 30.3% of patients suffering from depression and/or anxiety. Disease activity was found to be significantly associated with depression and/or anxiety (p = 0.01). Females were more likely to have anxiety (p = 0.01). Conclusion A significant proportion of IBD patients suffer from depression and/or anxiety. The rates of these mental illnesses would justify screening and referral for psychiatric treatment in clinics treating this population. Patients with active disease are particularly at risk for anxiety and depression.