Gauree G. Konijeti

Long-term intake of dietary fat and risk of ulcerative colitis and Crohn's disease

Introduction Dietary fats influence intestinal inflammation and regulate mucosal immunity. Data on the association between dietary fat and risk of Crohns disease (CD) and ulcerative colitis (UC) are limited and conflicting. Methods We conducted a prospective study of women enrolled in the Nurses’ Health Study cohorts. Diet was prospectively ascertained every 4 years using a validated semi-quantitative food frequency questionnaire. Self-reported CD and UC were confirmed through medical record review. We examined the effect of energy-adjusted cumulative average total fat intake and specific types of fat and fatty acids on the risk of CD and UC using Cox proportional hazards models adjusting for potential confounders. Results Among 170 805 women, we confirmed 269 incident cases of CD (incidence 8/100 000 person-years) and 338 incident cases of UC (incidence 10/100 000 person-years) over 26 years and 3 317 338 person-years of follow-up. Cumulative energy-adjusted intake of total fat, saturated fats, unsaturated fats, n-6 and n-3 polyunsaturated fatty acids (PUFAs) were not associated with risk of CD or UC. However, greater intake of long-chain n-3 PUFAs was associated with a trend towards lower risk of UC (HR 0.72, 95% CI 0.51 to 1.01). In contrast, high long-term intake of trans-unsaturated fatty acids was associated with a trend towards an increased incidence of UC (HR 1.34, 95% CI 0.94 to 1.92). Conclusions A high intake of dietary long-chain n-3 PUFAs may be associated with a reduced risk of UC. In contrast, high intake of trans-unsaturated fats may be associated with an increased risk of UC.

Cost-effectiveness of Competing Strategies for Management of Recurrent Clostridium difficile Infection: A Decision Analysis

BACKGROUND Clostridium difficile infection (CDI) is an important cause of morbidity and healthcare costs, and is characterized by high rates of disease recurrence. The cost-effectiveness of newer treatments for recurrent CDI has not been examined, yet would be important to inform clinical practice. The aim of this study was to analyze the cost effectiveness of competing strategies for recurrent CDI. METHODS We constructed a decision-analytic model comparing 4 treatment strategies for first-line treatment of recurrent CDI in a population with a median age of 65 years: metronidazole, vancomycin, fidaxomicin, and fecal microbiota transplant (FMT). We modeled up to 2 additional recurrences following the initial recurrence. We assumed FMT delivery via colonoscopy as our base case, but conducted sensitivity analyses based on different modes of delivery. Willingness-to-pay threshold was set at

Physical activity and risk of inflammatory bowel disease: prospective study from the Nurses’ Health Study cohorts

50 000 per quality-adjusted life-year. RESULTS At our base case estimates, initial treatment of recurrent CDI using FMT colonoscopy was the most cost-effective strategy, with an incremental cost-effectiveness ratio of

Pretreatment 25-Hydroxyvitamin D Levels and Durability of Anti–Tumor Necrosis Factor–α Therapy in Inflammatory Bowel Diseases

17 016 relative to oral vancomycin. Fidaxomicin and metronidazole were both dominated by FMT colonoscopy. On sensitivity analysis, FMT colonoscopy remained the most cost-effective strategy at cure rates >88.4% and CDI recurrence rates <14.9%. Fidaxomicin required a cost <

Venous thromboembolism in patients with inflammatory bowel diseases: a case-control study of risk factors.

1359 to meet our cost-effectiveness threshold. In clinical settings where FMT is not available or applicable, the preferred strategy appears to be initial treatment with oral vancomycin. CONCLUSIONS In this decision analysis examining treatment strategies for recurrent CDI, we demonstrate that FMT colonoscopy is the most cost-effective initial strategy for management of recurrent CDI.

Vitamin D Supplementation Modulates T Cell–Mediated Immunity in Humans: Results from a Randomized Control Trial

Objective To examine the association between physical activity and risk of ulcerative colitis and Crohn’s disease. Design Prospective cohort study. Setting Nurses’ Health Study and Nurses’ Health Study II. Participants 194 711 women enrolled in the Nurses’ Health Study and Nurses’ Health Study II who provided data on physical activity and other risk factors every two to four years since 1984 in the Nurses’ Health Study and 1989 in the Nurses’ Health Study II and followed up through 2010. Main outcome measure Incident ulcerative colitis and Crohn’s disease. Results During 3 421 972 person years of follow-up, we documented 284 cases of Crohn’s disease and 363 cases of ulcerative colitis. The risk of Crohn’s disease was inversely associated with physical activity (P for trend 0.02). Compared with women in the lowest fifth of physical activity, the multivariate adjusted hazard ratio of Crohn’s disease among women in the highest fifth of physical activity was 0.64 (95% confidence interval 0.44 to 0.94). Active women with at least 27 metabolic equivalent task (MET) hours per week of physical activity had a 44% reduction (hazard ratio 0.56, 95% confidence interval 0.37 to 0.84) in risk of developing Crohn’s disease compared with sedentary women with <3 MET h/wk. Physical activity was not associated with risk of ulcerative colitis (P for trend 0.46). The absolute risk of ulcerative colitis and Crohn’s disease among women in the highest fifth of physical activity was 8 and 6 events per 100 000 person years compared with 11 and 16 events per 100 000 person years among women in the lowest fifth of physical activity, respectively. Age, smoking, body mass index, and cohort did not significantly modify the association between physical activity and risk of ulcerative colitis or Crohn’s disease (all P for interaction >0.35). Conclusion In two large prospective cohorts of US women, physical activity was inversely associated with risk of Crohn’s disease but not of ulcerative colitis.

Natural history of perianal Crohn's disease after fecal diversion.

INTRODUCTION Emerging evidence supports an immunologic role for 25-hydroxyvitamin D (25(OH)D) in inflammatory bowel disease (IBD). Here we examined if pretreatment vitamin D status influences durability of anti-tumor necrosis factor (TNF)-α therapy in patients with Crohns disease (CD) or ulcerative colitis (UC). METHODS All IBD patients who had plasma 25(OH)D level checked <3 months prior to initiating anti-TNF-α therapy were included in this retrospective single-center cohort study. Our main predictor variable was insufficient plasma 25(OH)D (<30 ng/mL). Cox proportional hazards model adjusting for potential confounders was used to identify the independent effect of pretreatment vitamin D on biologic treatment cessation. RESULTS Our study included 101 IBD patients (74 CD; median disease duration 9 years). The median index 25(OH)D level was 27 ng/mL (interquartile range, 20-33 ng/mL). One-third of the patients had prior exposure to anti-TNF-α therapy. On multivariate analysis, patients with insufficient vitamin D demonstrated earlier cessation of anti-TNF-α therapy (hazard ratio [HR], 2.13; 95% confidence interval [CI], 1.03-4.39; P = .04). This effect was significant in patients who stopped treatment for loss of response (HR, 3.49; 95% CI, 1.34-9.09) and stronger for CD (HR, 2.38; 95% CI, 0.95-5.99) than UC (P = NS). CONCLUSIONS Our findings suggest that vitamin D levels may influence durability of anti-TNF-α induction and maintenance therapy. Larger cohort studies and clinical trials of supplemental vitamin D use with disease activity as an end point may be warranted.

Stool DNA Analysis is Cost-Effective for Colorectal Cancer Surveillance in Patients With Ulcerative Colitis

Background:Inflammatory bowel disease (IBD) is a well-known risk factor for venous thromboembolism (VTE). Existing guidelines for thromboprophylaxis in hospitalized patients do not extend to other clinical scenarios that may also be associated with VTE risk. Our aim was to estimate the fraction of VTE events in patients with IBD that could be prevented. Methods:A retrospective analysis assessed all patients with IBD diagnosed with VTE at a single academic medical center from 2002 to 2012. Confirmed cases were analyzed for VTE risk factors, inpatient status, the use of deep venous thrombosis prophylaxis, and when applicable the reason for omission of prophylaxis. IBD VTE cases were compared with age- and sex-matched non-IBD VTE controls with regards to risk factors and potential opportunities for VTE prevention. Results:There were 204 patients with IBD (108 ulcerative colitis, 96 Crohns disease) diagnosed with VTE (110 deep venous thrombosis, 66 pulmonary embolism, 27 intra-abdominal thromboses, and 1 other). One-third of the VTE events occurred in hospitalized patients. Two-third of the medical inpatients and 44% of surgical inpatients who developed VTE did not receive prophylaxis. Importantly, 129 VTE events occurred in outpatients. The proportion of outpatients hospitalized within 4 weeks of developing venous thrombosis was higher in patients with IBD than non-IBD controls (33% versus 15%, P = 0.0003). One-third (36%) of patients were experiencing ambulatory disease flares at the time of VTE diagnosis. Conclusions:A substantial portion of VTE events in patients with IBD occurred in clinical scenarios is not routinely recommended for thromboprophylaxis. Further investigation of primary prophylaxis for patients with IBD in high-risk outpatients may be warranted.

Ustekinumab for Moderate-to-Severe Crohn's Disease

CONTEXT Although studies have linked vitamin D deficiency with immune-mediated diseases, data demonstrating a direct effect on T-cell function are sparse. OBJECTIVE Our objective was to determine whether oral vitamin D3 influences T-cell activation in humans with vitamin D deficiency. DESIGN This was a single-center ancillary study within Vitamin D Therapy in Individuals at High Risk of Hypertension, a double-blind, multicenter, randomized controlled trial. SETTING This study was undertaken in a single academic medical center. PARTICIPANTS Adults with vitamin D deficiency and untreated pre- or early stage I hypertension were included. INTERVENTION In Vitamin D Therapy in Individuals at High Risk of Hypertension, participants were randomized to either low- (400 IU daily) or high- (4000 IU daily) dose oral vitamin D3 for 6 months. In this ancillary study of 38 patients, we measured CD4+ T-cell activation estimated by intracellular ATP release after stimulation of whole blood with plant lectin phytohemagglutinin collected at baseline (pretreatment) and 2-month follow-up. MAIN OUTCOME MEASURE Determining whether ATP level changes were significantly different between treatment groups was the main outcome measure. RESULTS Treatment with 4000 IU of vitamin D3 decreased intracellular CD4+ ATP release by 95.5 ng/ml (interquartile range, -219.5 to 105.8). In contrast, 400 IU of vitamin D3 decreased intracellular CD4+ ATP release by 0.5 ng/ml (interquartile range, -69.2 to 148.5). In a proportional odds model, high-dose vitamin D3 was more likely than low-dose vitamin D3 to decrease CD4+ ATP release (odds ratio, 3.43; 95% confidence interval, 1.06-1.11). CONCLUSIONS In this ancillary study of a randomized controlled trial, we found that high-dose vitamin D3 significantly reduced CD4+ T-cell activation compared to low-dose vitamin D3, providing human evidence that vitamin D can influence cell-mediated immunity.

Sa1779 Vitamin D Modulates T Cell-Mediated Immunity: Results From a Randomized Controlled Trial of Low-Dose and High-Dose Vitamin D3

Background:Temporary fecal diversion has been used to allow severe perianal Crohns disease (CD) to heal. Most data on intestinal reconnection rates precede the biological era with limited patient follow-up after reconnection. We, therefore, sought to evaluate the natural history of perianal CD after fecal diversion. Methods:We identified 49 patients with CD and perianal involvement who underwent fecal diversion between 1991 and 2011 at a tertiary referral care center. Demographics, medication use, onset and extent of disease, and surgical interventions were abstracted. We determined the percentage of patients who were able to restore intestinal continuity and assessed the sustainability of this reversal. Time to intestinal reconnection and subsequent procedures were determined. We also examined temporal trends in the proportion of patients with perianal CD undergoing diversion or management with seton/EUA/fistulotomy between 2000 and 2011. Results:Fifteen of 49 patients (31%) reestablished intestinal continuity during the study follow-up period. Ten of 15 patients (67%) who had reestablished intestinal continuity required an additional procedure to divert the fecal stream. Of the 5 patients who remained reconnected, 3 patients required further procedures to control sepsis. The proportion of patients with CD requiring perianal surgical interventions declined between 2000 and 2011. Conclusions:Severe perianal CD remains a challenging problem. In patients with CD with perianal disease requiring fecal diversion, the likelihood of sustained intestinal continuity remains low, despite greater biological use. However, there has been a temporal decline in the rate of surgical interventions required for perianal CD from 2000 to 2011.