Corrigendum to "Low Body Mass Index Can Identify Majority of Osteoporotic Inflammatory Bowel Disease Patients Missed by Current Guidelines".

[This corrects the article DOI: 10.1100/2012/807438.].

Impact of Low Immunoglobulin G Levels on Disease Outcomes in Patients with Inflammatory Bowel Diseases.

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.

Similar outcomes of IBD inpatients with Clostridium difficile infection detected by ELISA or PCR assay.

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.

Progressive primary sclerosing cholangitis requiring liver transplantation is associated with reduced need for colectomy in patients with ulcerative colitis.

BACKGROUND & AIMS: We investigated the association between the severity of primary sclerosing cholangitis (PSC) and clinical outcomes of patients with ulcerative colitis (UC) on the basis of need for colectomy. METHODS: We analyzed data from 167 patients with PSC and UC who were followed from 1985 to 2011. Patients with PSC and UC were divided into groups that received orthotopic liver transplantation (OLT) (n = 86) or did not (non-OLT, n = 81). Clinical and demographic variables were obtained, and patients were followed until they received OLT or the date of their last clinical visit. RESULTS: The OLT group had significantly more subjects with less severe symptoms of UC (59, 68.6%) than the non-OLT group (12, 14.8%; P < .001). The subjects in the OLT group had a median of 0 UC flares compared with 3 in the non-OLT group (P < .001); fewer subjects in the OLT group required use of azathioprine or mercaptopurine (1, 1.2%), compared with the non-OLT group (14, 17.3%; P = .006). More subjects in the non-OLT group required colectomies (61, 75.3%) than in the OLT group (23, 26.7%; P < .001). On the basis of Cox regression analysis, OLT for PSC independently reduces the need for colectomy (hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.25-0.75; P = .003), as does a high Mayo risk score at diagnosis (HR, 0.52; 95% CI, 0.37-0.72; P < .001). Development of colon neoplasia increased the risk for colectomy (HR, 2.47; 95% CI, 1.63-3.75; P < .001). CONCLUSIONS: Severe progressive PSC that requires liver transplantation appears to reduce the disease activity of UC and the need for colectomy.

Duration and severity of primary sclerosing cholangitis is not associated with risk of neoplastic changes in the colon in patients with ulcerative colitis.

BACKGROUND: Annual surveillance colonoscopy to detect colon cancer is recommended for patients with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC). Limited data currently support these recommendations. OBJECTIVE: To study whether a relationship exists between the severity and duration of PSC and the risk of colon cancer and dysplasia (colon neoplasia). DESIGN: Retrospective, longitudinal study. SETTING: Tertiary-care referral center. PATIENTS: Information pertaining to duration of PSC, UC, requirement for orthotopic liver transplantation, and time to diagnosis of colon neoplasia was obtained for patients with PSC and UC. Patients were evaluated and followed-up from 1985 to 2011 at a single institution. MAIN OUTCOME MEASUREMENTS: Association between the severity and duration of PSC-UC and the time of occurrence of colon neoplasia. RESULTS: Of 167 patients with a combined diagnosis of PSC-UC, 55 had colonic neoplasia on colonoscopy. Colonic neoplasia occurred more frequently within 2 years of a combined diagnosis of PSC-UC (6.6/100 patient-years of follow-up) than after 8 years from PSC-UC (2.7/100 patient-years of follow-up). On proportional hazards analysis, older age at PSC diagnosis (hazard ratio 1.23 for every 5 years; 95% confidence interval, 1.03-1.34; P = .014) increased the risk of colon neoplasia. LIMITATIONS: Retrospective study. CONCLUSION: In this study, the severity of PSC was not significantly associated with the risk of colon neoplasia. Patients with PSC and UC have a high risk of colon neoplasia soon after the coexistence of the two diseases is discovered. Older age at PSC diagnosis increases this risk.

Low body mass index can identify majority of osteoporotic inflammatory bowel disease patients missed by current guidelines.

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.

Risk factors for low bone mass in patients with ulcerative colitis following ileal pouch-anal anastomosis.

OBJECTIVES: Bone mineral density (BMD) can be adversely affected by the chronic nature of inflammatory bowel disease. Ileal pouch-anal anastomosis (IPAA) is the surgical treatment of choice for patients with ulcerative colitis (UC) who require proctocolectomy. There are few data on BMD in UC patients with IPAA. The aim of the study was to assess the prevalence and risk factors associated with low BMD in UC patients after IPAA. METHODS: A total of 327 eligible patients with UC and IPAA from the Pouchitis Clinic were enrolled. Dual-energy X-ray absorptiometry was performed. Patients were classified as having normal or low BMD, based on the criteria by the International Society for Clinical Densitometry. A total of 39 demographic and clinical variables were evaluated with logistic regression models. RESULTS: Of 327 patients with a median of 4 years after IPAA, 105 (32.1%) had low BMD. Fragility fracture was documented in 11 patients (10.5%) in the low BMD group and in 13 of 222 patients (5.9%) in the normal BMD group (P=0.14). In the multivariable analysis, covariate-adjusted factors associated with a low BMD were advanced age (odds ratio (OR) =1.64 per 5 years; 95% CI, 1.44-1.87), low body mass index (OR=0.43 per 5 kg/m(2); 95% CI, 0.30-0.62), and non-use of daily calcium supplement (OR=0.53; 95% CI, 0.29-0.96). Pouch-associated factors were not found to be significantly associated with the bone loss. CONCLUSIONS: Low BMD was common in patients with UC, even after colectomy and IPAA. Low BMD in this patient population was associated with certain risk factors, some of which may be modifiable.

Association between immune-associated disorders and adverse outcomes of ileal pouch-anal anastomosis.

OBJECTIVES: Autoimmune disorders (ADs) frequently coexist with inflammatory bowel disease. The aim of the study was to determine whether coexisting AD in patients with ileal pouches increases the risk for chronic antibiotic-refractory pouchitis (CARP) and other inflammatory conditions of the pouch. METHODS: A total of 622 patients seen in our Pouchitis Clinic were enrolled. We compared the prevalence of adverse outcomes of the pouch (including CARP, Crohn's disease of the pouch, and pouch failure) in patients with or without concurrent AD and assessed the factors for these adverse outcomes. RESULTS: There were seven pouch disease categories: normal (N=60), irritable pouch syndrome (N=112), active pouchitis (N=131), CARP (N=67), Crohn's disease (N=131), cuffitis (N=83), surgical complications (N=36), and anismus (N=2). The prevalence of AD in these pouch disease categories was 4.5%, 12.5%, 9.2%, 13.4%, 10.7%, 3.8%, 1.5%, and 0%, respectively. The presence of at least one AD at time of pouch surgery was shown to be associated with a twofold increase in the risk for CARP (hazard ratio=2.29; 95% CI: 1.52, 3.46; P<0.001) and for pouch-associated hospitalization (hazard ratio=2.39; 95% CI: 1.59, 3.58; P<0.001). The presence of AD was not associated with increased risk for irritable pouch syndrome, active pouchitis, Crohn's disease, cuffitis, surgical complications, or pouch failure. Patients with Crohn's disease of the pouch had a 2.42 times higher risk for pouch failure (P=0.042) than these without. Active smoking or a history of smoking was shown to be associated with an increased risk for pouch-associated hospitalization and pouch failure. CONCLUSIONS: AD appears to be associated with an increased risk for CARP, and the presence of the association between these AD and pouch disorders may stimulate further research on the link of these organ systems on an immunological basis.

A proposed classification of ileal pouch disorders and associated complications after restorative proctocolectomy.

Both medical and surgical therapies for ulcerative colitis have inherent advantages and disadvantages that must be balanced for patients with moderate to severe disease. Restorative proctocolectomy with ileal pouch-anal anastomosis has become the surgical treatment of choice for the majority of patients with ulcerative colitis who require proctocolectomy. However, adverse sequelae of mechanical, inflammatory, functional, neoplastic, and metabolic conditions related to the pouch can occur postoperatively. Recognition and familiarization of the disease conditions related to the ileal pouch can be challenging for practicing gastroenterologists. Accurate diagnosis and classification of the disease conditions are imperative for proper management and prognosis.

Using technology to promote gastrointestinal outcomes research: a case for electronic health records.

Electronic health records (EHRs) have been shown to reduce medication errors, improve patient outcomes, and create administrative efficiencies. Numerous public and private efforts are currently underway to achieve universal EHR adoption in the United States by the year 2014. EHRs hold a great potential to integrate clinical care and research by allowing input of clinical data in a structured format, facilitating electronic data capture for clinical trials and providing linkage with genomic information. The goal of this article is to inform the academic gastrointestinal community about the research opportunities created by the widespread adoption of EHRs and present a systematic approach in utilizing EHR-derived data for observational, experimental, or translational studies.

Severe complications of inflammatory bowel disease.

Patients who have inflammatory bowel disease occasionally develop severe complications or emergency situations that require expert and expedited medical care, including toxic colitis, fistulas, abdominal abscesses, malignancy, primary sclerosing cholangitis, and pouchitis. Morbidity and mortality rates of Crohn's disease and ulcerative colitis are increased over the expected rates in the unaffected population. Knowledge of the presenting features, natural history, and treatment of these complications should to lead to early and effective therapy and better outcomes.

Cost-effectiveness of quantitative fecal lactoferrin assay for diagnosis of symptomatic patients with ileal pouch-anal anastomosis.

BACKGROUND AND AIMS: To assess cost-effectiveness of fecal lactoferrin (FL) as the initial diagnostic approach to symptomatic patients with ileal pouch-anal anastomosis (IPAA). METHODS: Four competing strategies [empiric metronidazole therapy (txMTZ), initial pouch endoscopy with biopsy (testBiop), initial FL assay followed by metronidazole therapy (testFL+MTZ), and initial FL assay followed by pouch endoscopy and biopsy (testFL+Biop)] were modeled in a decision tree. RESULTS: In the base-case, the average cost per patient was $241 for testFL+MTZ, $251 for txMTZ, $405 for testFL+Biop, and $431 for testBiop. The testBiop strategy had greater effectiveness compared with txMTZ but at an incremental cost of $158 per day. The txMTZ strategy was slightly more costly and minimally more effective than testFL+MTZ with an incremental cost effectiveness of just over $12 per day. However, the testFL+MTZ strategy was associated with a 31% absolute reduction in antibiotic exposure compared with the txMTZ strategy. CONCLUSIONS: Compared with empiric metronidazole therapy, FL before treatment with metronidazole is less costly with less exposure to antibiotics and less need for endoscopy, with only marginal decrease in effectiveness.

Application of wireless capsule endoscopy for the evaluation of iron deficiency anemia in patients with ileal pouches.

BACKGROUND: Although wireless capsule endoscopy (WCE) is widely used in the assessment of small bowel pathology, its application in patients with ileal pouches has not been evaluated. Persistent anemia has been observed in patients with ileal pouches, for which identification of etiology can be challenging. AIM: To assess the utility of WCE in ileal pouch patients with persistent anemia in conjunction with other diagnostic modalities. METHODS: Ulcerative colitis patients with persistent anemia (hemoglobin <10 g/dL) at least 12 months after either ileal pouch-anal anastomosis or continent ileostomy surgery were studied. Esophagogastroduodenoscopy, pouch endoscopy, WCE, and celiac disease serology were studied. The final diagnosis of the etiology of anemia was based on the results from the combined assessment of clinical, endoscopic, histologic, and laboratory data. RESULTS: Seventeen ileal pouch patients (10 females, 7 males) with underlying inflammatory bowel disease were studied with a mean age 42.1+/-15.2 years. Nine patients (52.9%) had active pouchitis and 3 (17.6%) had Crohn's disease (CD). WCE was successfully completed in 16 patients (94.1%). Suspected causes of anemia were identified in 5 patients (29.4%): 2 patients with CD of the pouch and 1 patient with celiac disease, detected by esophagogastroduodenoscopy, pouch endoscopy, small bowel biopsy, and celiac disease serology, and 1 patient with CD of the small bowel and 1 patient with small bowel arterio-venous malformations shown on WCE only. CONCLUSIONS: WCE seemed to be feasible and well tolerated in patients with ileal pouches. WCE provided additional diagnostic information in the pouch patients with anemia.

Infliximab maintenance therapy for fistulizing Crohn's disease.

BACKGROUND: Infliximab, a monoclonal antibody against tumor necrosis factor, is an effective maintenance therapy for patients with Crohn's disease without fistulas. It is not known whether infliximab is an effective maintenance therapy for patients with fistulas. METHODS: We performed a multicenter, double-blind, randomized, placebo-controlled trial to evaluate the efficacy of infliximab maintenance therapy in 306 adult patients with Crohn's disease and one or more draining abdominal or perianal fistulas of at least three months' duration. Patients received 5 mg of infliximab per kilogram of body weight intravenously on weeks 0, 2, and 6. A total of 195 patients who had a response at weeks 10 and 14 and 87 patients who had no response were then randomly assigned to receive placebo or 5 mg of infliximab per kilogram every eight weeks and to be followed to week 54. The primary analysis was the time to the loss of response among patients who had a response at week 14 and underwent randomization. RESULTS: The time to loss of response was significantly longer for patients who received infliximab maintenance therapy than for those who received placebo maintenance (more than 40 weeks vs. 14 weeks, P<0.001). At week 54, 19 percent of patients in the placebo maintenance group had a complete absence of draining fistulas, as compared with 36 percent of patients in the infliximab maintenance group (P=0.009). CONCLUSIONS: Patients with fistulizing Crohn's disease who have a response to induction therapy with infliximab have an increased likelihood of a sustained response over a 54-week period if infliximab treatment is continued every 8 weeks.

Implementation of Clinical Pharmacogenomics within a Large Health System: From Electronic Health Record Decision Support to Consultation Services.

The number of clinically relevant gene-based guidelines and recommendations pertaining to drug prescribing continues to grow. Incorporating gene-drug interaction information into the drug-prescribing process can help optimize pharmacotherapy outcomes and improve patient safety. However, pharmacogenomic implementation barriers exist such as integration of pharmacogenomic results into electronic health records (EHRs), development and deployment of pharmacogenomic decision support tools to EHRs, and feasible models for establishing ambulatory pharmacogenomic clinics. We describe the development of pharmacist-managed pharmacogenomic services within a large health system. The Clinical Pharmacogenetics Implementation Consortium guidelines for HLA-B*57:01-abacavir, HLA-B*15:02-carbamazepine, and TPMT-thiopurines (i.e., azathioprine, mercaptopurine, and thioguanine) were systematically integrated into patient care. Sixty-three custom rules and alerts (20 for TPMT-thiopurines, 8 for HLA-B*57:01-abacavir, and 35 for HLA-B*15:02-anticonvulsants) were developed and deployed to the EHR for the purpose of providing point-of-care pharmacogenomic decision support. In addition, a pharmacist and physician-geneticist collaboration established a pharmacogenomics ambulatory clinic. This clinic provides genetic testing when warranted, result interpretation along with pharmacotherapy recommendations, and patient education. Our processes for developing these pharmacogenomic services and solutions for addressing implementation barriers are presented.

Autoimmune features are associated with chronic antibiotic-refractory pouchitis.

BACKGROUND: 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. METHODS: We 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. RESULTS: Autoimmune 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. CONCLUSIONS: There 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.

Colorectal cancer surveillance for patients with inflammatory bowel disease.

Although the cumulative prevalence of colorectal cancer among patients with ulcerative colitis is similar to that among patients with sporadic colorectal cancer, the younger age of ulcerative colitis patients with cancer accounts for the age-specific relative risk. Approximately half of ulcerative colitis patients with colorectal cancer die from metastatic disease. Pancolitis of long duration and coexistent primary sclerosing cholangitis are strong risk factors for cancer that should prompt entry into cancer surveillance programs. When done appropriately, cancer surveillance in patients with inflammatory bowel disease can be very effective, and at a reasonable cost.

Motion - colonoscopic surveillance is more cost effective than colectomy in patients with ulcerative colitis: Arguments for the motion.

Patients with ulcerative colitis (UC) are at increased risk for colorectal cancer (CRC), especially those with longstanding disease, pancolitis or primary sclerosing cholangitis. The incidence of colitis- associated cancer is increasing, and the mortality rates from CRC are higher in UC patients than in the general population. Case control studies have demonstrated that surveillance colonoscopy reduces the risk of dying from CRC. A well conducted decision analysis found that surveillance colonoscopy decreases cancer-related mortality and increases life expectancy. The results with surveillance programs were almost as good as with prophylactic colectomy. A subsequent cost effectiveness analysis using the same model found that, compared with a policy of no surveillance, colonoscopic surveillance was more effective at preventing death from CRC and was less costly. The best strategy appears to be to perform colonoscopies every three years. The analysis also showed that colectomy should be recommended in patients with low-grade dysplasia. Patients at very high risk for CRC should undergo yearly colonoscopy, and patients who are concerned about the limitations of this technique should be offered prophylactic colectomy.