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Infliximab, a monoclonal antibody against tumor necrosis factor, reduces disease activity in patients with Crohn's disease. In this study of patients with fistulizing Crohn's disease who had a response to infliximab, continued infusions every 8 weeks were associated with a longer duration of response than were placebo infusions. After 54 weeks of treatment, 36 percent of patients in the infliximab group and 19 percent of those in the placebo group had no draining fistulas. Maintenance treatment reduced the likelihood of relapse. Fistulas occur in 17 to 43 percent of patients with Crohn's disease. 1 , 2 Perianal fistulas, the most common variant, decrease the quality of life and increase the likelihood of total colectomy. 3 Although widely used in the treatment of fistulas, antibiotics, immunomodulators, and dietary therapies have not been demonstrated to result in sustained closure of fistulas in Crohn's disease. 4 – 9 Surgical options are limited by the potential for compromise of anal continence. Surgical diversion of the fecal stream by a stoma often produces healing; however, many patients find a stoma to be undesirable, and the benefit of this approach is unlikely . . .

In the article titled “Low Body Mass Index Can Identify Majority of Osteoporotic Inflammatory Bowel Disease Patients Missed by Current Guidelines” [1], there was an error regarding the FRAX® tool, which should be clarified as follows.

SummaryMetronidazole is effective for the treatment of acute pouchitis after ileal pouch–anal anastomosis, but it has not been directly compared with other antibiotics. This randomized clinical trial was designed to compare the effectiveness and side effects of ciprofloxacin and metronidazole for treating acute pouchitis. Acute pouchitis was defined as a score of 7 or higher on the 18-point Pouchitis Disease Activity Index (PDAI) and symptom duration of 4 weeks or less. Sixteen patients were randomized to a 2-week course of ciprofloxacin 1,000 mg/d (n = 7) or metronidazole 20 mg/kg/d (n = 9). Clinical symptoms, endoscopic findings, and histologic features were assessed before and after therapy. Both ciprofloxacin and metronidazole produced a significant reduction in the total PDAI score as well as in the symptom, endoscopy, and histology subscores. Ciprofloxacin lowered the PDAI score from 10.1 ± 2.3 to 3.3 ± 1.7 (p = 0.0001), whereas metronidazole reduced the PDAI score from 9.7 ± 2.3 to 5.8 ± 1.7 (p = 0.0002). There was a significantly greater reduction in the ciprofloxacin group than in the metronidazole group in terms of the total PDAI (6.9 ± 1.2 versus 3.8 ± 1.7; p = 0.002), symptom score (2.4 ± 0.9 versus 1.3 ± 0.9; p = 0.03), and endoscopic score (3.6 ± 1.3 versus 1.9 ± 1.5; p = 0.03). None of patients in the ciprofloxacin group experienced adverse effects, whereas three patients in the metronidazole group (33%) developed vomiting, dysgeusia, or transient peripheral neuropathy. Both ciprofloxacin and metronidazole are effective in treating acute pouchitis with significant reduction of the PDAI scores. Ciprofloxacin produces a greater reduction in the PDAI and a greater improvement in symptom and endoscopy scores, and is better tolerated than metronidazole. Ciprofloxacin should be considered as one of the first-line therapies for acute pouchitis.

Background. Patients with inflammatory bowel disease (IBD) are at high risk of developing osteoporosis. Our objective was to determine the usefulness of IBD guidelines in identifying patients at risk for developing osteoporosis. Methods. We utilized institutional repository to identify patients seen in IBD center and extracted data on demographics, disease history, conventional, and nonconventional risk factors for osteoporosis and Dual Energy X-ray Absorptiometry (DXA) findings. Results. 59% of patients (1004/1703) in our IBD cohort had at least one risk factor for osteoporosis screening. DXA was documented in 263 patients with indication of screening (provider adherence, 26.2%), and of these, 196 patients had DXA completed (“at-risk” group). Ninety-five patients not meeting guidelines-based risk factors also had DXA completed (“not at-risk” group). 139 (70.9%) patients in “at-risk” group had low BMD, while 51 (53.7%) of “not-at-risk” patients had low BMD. Majority of the patients with osteoporosis (83.3%) missed by the current guidelines had low BMI. Multivariate logistic regression analysis showed that low BMI was the strongest risk factor for osteoporosis (OR 3.07; 95% CI, 1.47–6.42; P=0.003). Conclusions. Provider adherence to current guidelines is suboptimal. Low BMI can identify majority of the patients with osteoporosis that are missed by current guidelines.

Chronic antibiotic-refractory pouchitis (CARP) occurs more frequently in patients with ileal pouch–anal anastomosis (IPAA) with concomitant autoimmune disorders. The aim of this study was to assess the overlap between dysregulated immune features in patients with IPAA and their association with CARP.MethodsWe identified 150 symptomatic patients with IPAA who met inclusion criteria, including measurement of select autoimmune serology. Demographic and clinical variables were compared between patients with and without CARP.ResultsAutoimmune thyroid disease was more frequent among patients with CARP. The frequency of primary sclerosing cholangitis (16.7% versus 5.3%; P = 0.04) and serum positivity for microsomal antibody (25% versus 6.1%, P = 0.003) were significantly greater in patients with CARP compared with non-CARP patients, respectively. Increased tissue infiltration by IgG4-expressing plasma cells was detected in 17 of 31 patients (54.8%) in the CARP group as compared with 10/67 (14.9%) in the non-CARP group (P = 0.0001). Forty-seven percent of patients in the CARP group versus 22.8% in the non-CARP group had at least 2 immune features (P = 0.019). Among patients with IgG4 histology, 87% of patients in the CARP group versus 60% in the non-CARP group had at least 1 immune marker (P = 0.004). On multivariate analysis, microsomal antibody expression (odds ratio, 6.8; 95% confidence interval, 1.3–42.6; P = 0.02) and increased IgG4-expressing plasma cells tissue infiltration (odds ratio, 9.6; 95% confidence interval, 3.2–32.6, P = 0.0001) were risk factors for CARP.ConclusionsThere is marked overlap of certain immune markers in patients with pouch dysfunction, especially those with CARP. Microsomal antibody expression and elevated IgG4-positive plasma cell infiltration were independent risk factors for CARP.

Background Inflammatory bowel diseases (IBDs) are considered immune-mediated disorders with dysregulated innate and adaptive immunities. Secondary immunogloblin deficiency can occur in IBD and its impact on the disease course of IBD is not clear. Aims We sought to determine associations between low IgG/G1 levels and poor clinical outcomes in IBD patients. Methods This historic cohort study was performed on IBD patients with obtained IgG/IgG1 levels. The primary outcome was defined as any IBD-related bowel resection surgery and/or hospitalization. Subgroup analyses assessed particular surgical outcomes in Crohn’s disease (CD), ulcerative colitis (UC) or indeterminate colitis (IC), and ileal pouch–anal anastomosis (IPAA). The secondary outcomes included IBD drug escalations and C. difficile or cytomegalovirus infections. Results A total of 136 IBD patients had IgG/G1 levels checked and adequate follow-up, 58 (42.6 %) with normal IgG/G1 levels and 78 (57.4 %) having low levels. A total of 49 patients (62.8 %) with low immunoglobulin levels had IBD-related surgeries or hospitalizations, compared to 33 patients (56.9 %) with normal levels [odds ratio (OR) 1.28, 95 % confidence interval (CI) 0.64–2.56; p  = 0.49]. Low IgG/G1 levels were associated with IBD-related surgery in CD in univariate analysis [hazard ratio (HR) 4.42, 95 % CI 1.02–19.23; p  = 0.048] and in Kaplan–Meier survival curve analysis ( p  = 0.03), with a trend toward significance on multivariate analysis (HR 3.07, 95 % CI 0.67–14.31; p  = 0.15). IBD patients with low IgG/G1 levels required more small bowel resections (12.8 vs. 1.7 %, p  = 0.024) and 5-aminosalicylate initiations (28.2 vs. 13.8 %, p  = 0.045). Conclusions Our study demonstrated a possible association between low IgG/G1 levels and poor outcomes in CD including surgery. Future implications include using immunoglobulin levels in IBD patients as a prognostic indicator or boosting humoral immunity as a treatment in this subset.

Background Clostridium difficile infection (CDI) is known as a risk factor for exacerbation of inflammatory bowel disease (IBD). CDI has been most commonly tested with enzyme-linked immunosorbent assay for toxins, but with a suboptimal sensitivity. Compared with conventional ELISA, the polymerase chain reaction-based assay (PCR) is a highly sensitive detection technique for C. difficile . However, its pure detection of only the DNA of toxin B may lead to over-treatment. Aims The purpose of this study was to compare the frequency and clinical outcomes of IBD inpatients with CDI between the PCR and ELISA assays and to assess the factors associated with CDI. Methods The retrospective study was performed with the IBD inpatients at Cleveland Clinic from 2009 to 2011, who were tested by either ELISA or PCR or both. Outcomes under comparison included intensive care unit transfer, length of hospital stay, requirement for gastrointestinal surgeries and all cause re-hospitalization. Multivariable analysis was performed to assess the associated factors for the combined cohorts. Results A total of 255 patients were included, among them 222 had ELISA test, and 103 had PCR test. Thirteen (5.9 %) patients were ELISA positive, versus 14 (13.5 %) patients who were PCR positive ( P  = 0.02). With comparable demographic and clinical background, clinical outcomes of the ELISA and PCR positive groups showed no significant difference. Instead, the overall percentage of C. difficile positive patients had a much higher rehospitalization rate than C. difficile negative patients ( P  < 0.01). Multivariable analysis identified comorbidities ( P  = 0.03), extra-intestinal manifestations ( P  = 0.03) and PPI use ( P  < 0.01) as the associated factors for CDI. Conclusion There was a greater percentage of patients tested positive by PCR compared to ELISA. The outcomes of CDI diagnosed by PCR or ELISA, however, appeared comparable. The presence of comorbidities, extra-intestinal manifestations, and the use of PPI were found to be associated with CDI.

BackgroundPrimary sclerosing cholangitis (PSC) confers an increased risk of colon cancer in patients with inflammatory bowel disease (IBD). However, there is a scarcity of data to determine whether the rate of colon cancer changes after liver transplantation (LT) in IBD patients with PSC. The aims were 1) to estimate the risk of colon neoplasia after LT in IBD patients with PSC; 2) to identify the factors associated with colon neoplasia after LT in IBD patients with PSC.MethodsWe identified patients with IBD/PSC who underwent LT from 1998–2005 (n = 43). Two control groups were identified. Control 1 was IBD/PSC who did not undergo LT, matched 1:1 for age, gender, and type of IBD. Control 2 was patients with chronic liver disease other than PSC who underwent LT, matched 1:1 for age, gender, and follow-up time since LT. All patients were monitored by serial colonoscopy. Logistic regression analysis was used.ResultsDuring a mean follow-up of 54.7 ± 47.7 months, patients with IBD/PSC who underwent LT had similar rate of colon neoplasia compared to those who did not have LT (34% versus 30%, P = 0.24). The rate of colon neoplasia in LT recipients was higher in PSC patients compared to those with other forms of chronic liver disease (34% versus 0%, P = 0.018). Post-LT cytomegalovirus infection was associated with higher likelihood of colon neoplasia post-LT in IBD/PSC patients (hazard ratio = 4.4, P = 0.024). There was no significant difference in survival outcome between the three study groups.ConclusionsIBD/PSC patients remain at an increased risk of colon neoplasia after LT.