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Mesenteric adipose tissue (MAT) has gained substantial attention as an active player in Crohn's disease (CD), but its clinical significance is poorly understood and likely reflects, in part, difficulties assessing MAT noninvasively. Recent radiologic studies have identified candidate surrogate markers that may reflect inflammatory alterations of MAT in CD and have found that certain features including visceral adipose tissue may inform risk of complicated disease behavior, risk for surgery, and postoperative outcomes. Additionally, emerging surgical data have suggested MAT may even be a therapeutic target to mitigate postoperative recurrence of CD. However, the current studies have variable results, reduced sample sizes, and methodological limitations that preclude incorporating the radiologic and surgical findings into clinical practice. Nonetheless, the results are promising and potentially have important implications for the medical and surgical management of CD, which merits that additional studies are warranted. Thus, we have reviewed the available literature on the medical and surgical implications of MAT in CD to summarize our current understanding and identify gaps in knowledge to inform future investigations.Alterations in the mesenteric adipose tissue are actively involved in Crohn’s disease, but their clinical significance is unclear. We review the literature to understand the medical and surgical implications of mesenteric adipose tissue in Crohn’s disease to inform future investigations.

Obesity is variably associated with treatment response in biologic-treated patients with inflammatory bowel diseases (IBD). We evaluated the association between obesity and risk of hospitalization, surgery, or serious infections in patients with IBD in new users of biologic agents in a large, multicenter, electronic health record (EHR)-based cohort (CA-IBD).We created an EHR-based cohort of adult patients with IBD who were new users of biologic agents (tumor necrosis factor [TNF-α] antagonists, ustekinumab, and vedolizumab) between January 1, 2010, and June 30, 2017, from 5 health systems in California. Patients were classified as those with normal body mass index (BMI), overweight, or obese based on the World Health Organization classification. We compared the risk of all-cause hospitalization, IBD-related surgery, or serious infections among patients with obesity vs those overweight vs those with normal BMI, using Cox proportional hazard analyses, adjusting for baseline demographic, disease, and treatment characteristics.Of 3,038 biologic-treated patients with IBD (69% with Crohn's disease and 76% on TNF-α antagonists), 28.2% (n = 858) were overweight, and 13.7% (n = 416) were obese. On a follow-up after biologic initiation, obesity was not associated with an increased risk of hospitalization (adjusted hazard ratio [aHR] vs normal BMI, 0.90; [95% confidence interval, 0.72-1.13]); IBD-related surgery (aHR, 0.62 [0.31-1.22]); or serious infection (aHR, 1.11 [0.73-1.71]). Similar results were observed on stratified analysis by disease phenotype (Crohn's disease vs ulcerative colitis) and index biologic therapy (TNF-α antagonists vs non-TNF-α antagonists).In a multicenter, EHR-based cohort of biologic-treated patients with IBD, obesity was not associated with hospitalization, surgery, or serious infections. Further studies examining the effect of visceral obesity on patient-reported and endoscopic outcomes are needed.

Background Data describing the effect of obesity on antitumor necrosis factor (anti-TNF) treatment response are inconsistent. Visceral adipose tissue (VAT) is a superior marker of adiposity to body mass index. However, its effect on treatment response is unclear. We aimed to evaluate the effect of VAT on anti-TNF treatment response. Methods Inflammatory bowel disease (IBD) patients starting anti-TNF agents between January 1, 2009, and July 31, 2019, were included. 3-dimensional measurements of VAT volume and visceral fat index (visceral:subcutaneous adipose tissue ratio; VFI) were obtained from computed tomography (CT) scans. Subjects were categorized by predefined volume cutoffs ( Results The final cohort included 176 patients. No significant differences in treatment response at 6 months was observed. At 12 months, compared with volume Conclusions We found VAT volume is associated with anti-TNF treatment response in a nondose dependent manner, and VFI may inform risk of surgery after anti-TNF initiation. If confirmed by prospective studies, VAT volumetrics are potentially useful biomarkers to inform IBD treatment decisions.

With an increasing number of available therapies for inflammatory bowel disease (IBD), little is known about patients’ attitudes regarding IBD-related direct-to-consumer advertising (IBD-DTCA) and its impact on treatment decisions in clinical practice. We administered a 58-item, mailed questionnaire to patients with IBD receiving Gastroenterology subspecialty care at a large academic health system. The survey assessed patient awareness and perception of IBD-DTCA and its effect on IBD treatment discussions and decisions. We used bivariate analysis to evaluate patient-level factors associated with awareness and favorable perception of IBD-DTCA. We achieved a response rate of 15.2% (n = 226 of 1486). Most patients (93.3%) reported awareness of IBD-DTCA, with adalimumab receiving the most exposure. A majority of respondents reported IBD-DTCA made them more aware of treatments they otherwise would not know about (53.6%), provided information in a balanced manner (63.5%), and taught them about new potential risks and side effects (64.5%). Patients without a college degree and those with a household income less than $75 k per year perceived IBD-DTCA more favorably. However, IBD-DTCA rarely changed IBD management, with only 7.6% of respondents having a discussion with their provider about the advertised drug and only two (0.9%) being initiated on the advertised drug. IBD patients were aware of IBD-DTCA and perceived it favorably; however, IBD-DTCA rarely led to patient-provider discussions or changes in treatment regimen.

Crohn's disease (CD) is chronic immune-related disease of the gastrointestinal tract hypothesized to be caused by an interplay of genetic predisposition and environmental exposures. With the global incidence increasing, more patients are exploring dietary exposures to explain and treat CD. However, most patients report minimal nutritional education from their provider, and providers report few nutritional resources to help them educate patients. This highlights the previous deficit of literature describing the role and influence of diet in CD. To address this need, this article reviews available literature on the possible roles of diet in the pathogenesis, exacerbation, and treatment of CD.

OBJECTIVES: Despite the importance of adequate bowel cleansing prior to colonoscopy, national societies provide little guidance regarding which bowel preps are best tolerated and most effective; this reflects a lack of comparative effectiveness studies that directly evaluate available preps in a “real-world” setting. To address this gap, we conducted a prospective, naturalistic, commercially unfunded, comparative effectiveness study of currently available bowel preps and measured their impact on bowel cleansing. METHODS: We included patients ≥18 years old who presented for an outpatient colonoscopy at a large medical center serving >70 academic and community-based endoscopists who are free to prescribe the bowel prep of their choice. The primary outcome was bowel cleansing quality as measured by the Boston Bowel Preparation Scale (BBPS). The secondary outcome was prep tolerability. We performed regression models with random effects on the outcomes to adjust for confounding. RESULTS: There were 4339 colonoscopies performed by 75 endoscopists. Magnesium citrate, Miralax® with Gatorade®, Moviprep®, Osmoprep®, Prepopik®/Clenpiq®, and Suprep® all had significantly higher prep tolerability compared to GoLYTELY® (all p

OBJECTIVE: Little is known about the agreement between referring providers' reason for specialty evaluation and patients' understanding of why they are referred for consultation. Here, we compared the reason for consult (RFC) documented by referring providers during usual care vs. the perceived RFC independently reported by patients through an e-portal just prior to the specialist visit. METHODS: We performed an observational study among patients referred for gastrointestinal (GI) evaluation. Patients referred to the specialty clinic submitted their self-reported RFC using an online patient agenda form prior to their visit. Therefore, each participant had a referring provider- and patient-documented RFC. Blinded physicians reviewed the RFCs in random order using a priori coding criteria. We then compared whether the provider and patient RFC pairs were concordant (i.e., ≥1 clinical topic[s] in the RFCs matched). RESULTS: Sixty patients completed the e-portal prior to their visit, leading to 60 provider-patient RFC pairs. The RFC pairs were concordant in only 52% of cases. CONCLUSIONS: There is poor agreement between referring providers' reason for GI referral and patients' understanding of why they are visiting the clinic. Future research examining whether electronic patient agenda forms impact diagnostic and management precision, patient satisfaction, and healthcare utilization is warranted.

OBJECTIVE Inflammatory bowel diseases (IBD) are associated with significant morbidity and economic burden. The variable course of IBD creates a need for predictors of clinical outcomes and health resource utilization (HRU) to guide treatment decisions. We aimed to identify clinical, serological or genetic markers associated with inpatient resource utilization in patients with ulcerative colitis (UC) and Crohn's disease (CD). METHODS Patients with IBD with available genetic and serological data who had at least one emergency department visit or hospitalization in a 3-year period were included. The primary outcome measure was HRU, as measured by the All Patient Refined Diagnosis Related Group classification system. Univariate and multivariate linear and logistic regression models were used to identify the associations with HRU. RESULTS Altogether 858 (562 CD and 296 UC) patients were included. Anti-CBir1 seropositivity (P = 0.002, effect size [ES]: 0.762, 95% confidence interval [CI] 0.512-1.012) and low socioeconomic status (P = 0.005, ES: 1.620 [95% CI 1.091-2.149]) were independently associated with a high HRU. CD diagnosis (P = 0.006, ES: -0.701 [95% CI -0.959 to -0.443]) was independently associated with a low inpatient HRU. CONCLUSION In patients with IBD who required at least one emergency department visit or hospitalization, anti-CBir1 antibody status may be a useful biomarker of HRU when formulating management strategies to reduce disease complications and resource utilization.

Background Increased visceral adipose tissue (VAT) is associated with systemic inflammation through amplified production of pro-inflammatory cytokines like TNF-α and interleukin-6. Higher visceral fat index (VFI), which is the ratio of VAT to subcutaneous adipose tissue (SAT) and reflects the degree of excess VAT in relation to SAT, is associated with complex IBD. However, its relevance to treatment response is unclear. We aim to evaluate the effect of VFI on treatment response and risk of surgery in IBD patients starting anti-TNF therapy. Methods IBD patients starting anti-TNF agents between 1/1/2009 to 7/31/2019 at two academic medical centers were included. Three dimensional VAT and SAT volumes were measured from CT scans with Aquarius (iNtuition, Foster City, CA). VFI was calculated with the ratio of VAT:SAT. Patients were categorized by predefined VFI cutoffs: 0.67. Primary outcomes included composite endpoint of corticosteroid-free response (CFR) at 6 and 12 months defined by meeting one of the following: a) clinical response based on Harvey Bradshaw Index for Crohn’s disease (CD) or Lichtiger score for ulcerative colitis (UC), b) endoscopic improvement based on ulcer healing for CD and Mayo score for UC compared to baseline, or c) 50% improvement or normalization of CRP or fecal calprotectin. Secondary outcomes included IBD-related surgery at 6 and 12 months. We performed a multivariable logistic regression on CFR and surgery, adjusting for age, gender, IBD diagnosis, disease duration, active tobacco use, and immunomodulator exposure, to calculate adjusted odds ratio (aOR) and 95% confidence interval (CI). Results We included 181 patients. Table 1 summarizes differences in baseline characteristics. There were no differences in disease severity or activity. There were no differences in CFR at 6 and 12 months (Figure 1a and b). With respect to surgery within 6 months, patients with VFI >0.67 were significantly more likely to undergo surgery (aOR: 41.92 [95%CI 5.09–345.59]), but no difference in patients with VFI 0.33–0.66 was observed when compared to patients with VFI 0.67 were more likely to undergo surgery (aOR: 15.55 [95%CI 2.85–80.56]) but no difference was observed in patients with VFI 0.33–0.66 compared to patients with VFI Conclusion In this retrospective, multicenter, cohort study, we found higher VFI is associated with increased odds of surgery in IBD patients starting anti-TNF therapy. If confirmed by future prospective studies, VFI may be employed as a biomarker to help identify IBD patients at risk for medically refractory disease and would benefit from an early surgical referral, especially considering the growing application of artificial intelligence in medical imaging.

Background Biological therapies are effective for inducing and maintaining remission in inflammatory bowel disease (IBD), but patients often require changes in biological agents over the course of their illness. We sought to evaluate the rate of and reasons for discontinuing biological agents and to identify risk factors for their discontinuation. Methods We performed a retrospective cohort study across 4 VA hospital systems (Dallas, TX; Houston, TX; Ann Arbor, MI; Richmond, VA). Patients with IBD who were started on biological therapy between 1998 and 2015 were identified, and their medical records were reviewed to confirm the diagnosis of IBD and to collect study data. Results Of 1969 patients with IBD; 256 were treated with 346 courses of therapy. By 6 months after initiation of therapy, 82 (24%) had stopped the biological agent. Among patients starting their first biological agent, 21.5% had stopped by 6 months. Patients taking a concomitant thiopurine and those with ileocolonic disease or a nonpenetrating, nonstricturing phenotype were less likely to discontinue biological therapy, whereas those taking 5-ASA concomitantly were more likely to discontinue biological therapy. The most common reasons for discontinuation were primary nonresponse (40%) and adverse drug reactions (29%). Conclusions In conclusion, in a large multicenter VA cohort, we found that 24% of patients who are prescribed a biological stop their treatment early, most commonly for primary nonresponse or for an adverse drug reaction. Consideration should be given to treating patients with a concomitant thiopurine if at all possible, as this reduces the likelihood of early discontinuation.

Predicting the risk of flare-ups for patients with inflammatory bowel disease (IBD) is difficult. Alterations in gut endothelial regulation of mucosal immune homeostasis might be early events leading to flares in IBD. Cell adhesion molecules (CAMs), in particular, are important in maintaining endothelial integrity and regulating the migration of leukocytes into the gut. We evaluated the mRNA expression of various tight junction proteins, with an emphasis on CAMs, in 40 patients with IBD in clinical remission. Patients were retrospectively assessed at 6, 12, and 24 months after baseline colonoscopy, and at the end of all available follow-up (maximum 65 mo), for flare events to determine whether baseline mRNA expression was associated with subsequent flares. At all follow-up points, the baseline expression of platelet endothelial cell adhesion molecule-1 (PECAM-1), ICAM-3, and VCAM-1 was significantly higher in patients who flared than in those who did not (2.4-fold elevation, P=0.012 for PECAM-1; 1.9-fold increased, P=0.03 for ICAM-3; and 1.4-fold increased, P=0.02 for VCAM-1). PECAM-1 and ICAM-3 expression was significantly increased in patients who flared as early as 6 months after baseline colonoscopy. In contrast, there were no significant differences between patients with and without flares in baseline expression of other CAMs (ESAM, ICAM-1, ICAM-2, E-selectin, P-selectin, and MadCAM1). Increased expression of PECAM-1, ICAM-3, and VCAM-1 in colonic biopsies from patients with IBD in clinical remission is associated with subsequent flares. This suggests that increases in the expression of these proteins may be early events that lead to flares in patients with IBD.

With an increasing number of available therapies for inflammatory bowel disease (IBD), little is known about patients' attitudes regarding IBD-related direct-to-consumer advertising (IBD-DTCA) and its impact on treatment decisions in clinical practice.We administered a 58-item, mailed questionnaire to patients with IBD receiving Gastroenterology subspecialty care at a large academic health system. The survey assessed patient awareness and perception of IBD-DTCA and its effect on IBD treatment discussions and decisions. We used bivariate analysis to evaluate patient-level factors associated with awareness and favorable perception of IBD-DTCA.We achieved a response rate of 15.2% (n = 226 of 1486). Most patients (93.3%) reported awareness of IBD-DTCA, with adalimumab receiving the most exposure. A majority of respondents reported IBD-DTCA made them more aware of treatments they otherwise would not know about (53.6%), provided information in a balanced manner (63.5%), and taught them about new potential risks and side effects (64.5%). Patients without a college degree and those with a household income less than $75 k per year perceived IBD-DTCA more favorably. However, IBD-DTCA rarely changed IBD management, with only 7.6% of respondents having a discussion with their provider about the advertised drug and only two (0.9%) being initiated on the advertised drug.IBD patients were aware of IBD-DTCA and perceived it favorably; however, IBD-DTCA rarely led to patient-provider discussions or changes in treatment regimen.

Breath testing (BT) has gained interest for diagnosing small intestinal bacterial overgrowth (SIBO) in IBD patients with irritable bowel syndrome (IBS) overlap. We aim to characterize the rate of SIBO and BT gas patterns in IBD patients with IBS-like symptoms compared to non-IBD patients. A database of 14,847 consecutive lactulose BTs was developed from patients with IBS-like symptoms between November 2005 and October 2013. BTs were classified as normal, H2 predominant, CH4 predominant, and flatline based on criteria established from the literature. BT data linkage with electronic health records and chart review identified IBD patients along with disease phenotype, location, severity, and antibiotic response. Poisson loglinear model evaluated differences in gas patterns between the two groups. After excluding patients with repeat breath tests, we identified 486 IBD and 10,505 non-IBD patients with at least one BT. Positive BT was present in 57% (n = 264) of IBD patients. Crohn’s disease (odds ratio (OR) 0.21, [95% confidence interval (CI) 0.11–0.38]) and ulcerative colitis (OR 0.39, [95% CI 0.22–0.70]) patients were less likely to produce excess CH4. IBD patients were more likely to have flatline BT (OR 1.82, [95% CI 1.20–2.77]). In IBD patients with SIBO, 57% improved symptomatically with antibiotics. In a cohort of IBD patients with IBS-like symptoms, a high rate of patients had positive BT and symptomatic improvement with antibiotics. In IBD, methanogenesis is suppressed and flatline BT is more frequent, suggesting excess hydrogenotrophic bacteria. These findings suggest methanogenic and hydrogenotrophic microorganisms as potential targets for microbiome-driven biomarkers and therapies.

Background Data describing the effect of obesity on anti-TNF treatment response in inflammatory bowel disease (IBD) are conflicting. This likely reflects the shortcomings of using body mass index (BMI) to capture an individual’s adipose stores. Recent studies have found visceral adipose tissue (VAT), not BMI, is associated with IBD-related complications and post-operative recurrence. However, the relationship between VAT and treatment response is unclear. We aim to evaluate the effect of VAT on anti-TNF treatment response. Methods IBD patients starting anti-TNF agents between 1/1/2009 to 7/31/2019 at two academic medical centers were included. Three-dimensional VAT volume was measured from CT scans with Aquarius (iNtuition, Foster City, CA). Patients were categorized by predefined volume cutoffs: 3000cm3. Primary outcomes included composite endpoint of corticosteroid-free response (CFR) at 6 and 12 months defined by meeting one of the following: a) clinical response based on Harvey Bradshaw Index for Crohn’s disease (CD) or Lichtiger score for ulcerative colitis (UC) b) endoscopic improvement based on ulcer healing for CD and Mayo score for UC compared to baseline or c) 50% improvement or normalization of CRP or fecal calprotectin. Secondary outcomes included IBD-related surgery at 6 and 12 months. We performed a multivariable logistic regression on CFR and surgery, adjusting for age, gender, IBD diagnosis, disease duration, active tobacco use, and immunomodulator exposure, to calculate adjusted odds ratio (aOR) and 95% confidence interval (CI). Results We included 182 patients. Table 1 summarizes differences in baseline characteristics. There were no differences in CFR at 6 months. Compared to those with VAT volume 3000cm3 (aOR 0.45, [95%CI 0.13–1.50], Figure 1b). With respect to surgery within 6 months, patients with volume >3000cm3 were significantly more likely to undergo surgery than those with VAT volume 3000cm3 having the highest risk of surgery (aOR: 3.55 [95%CI 0.87–14.61], Figure 1c and d). Conclusion In this retrospective, multicenter, cohort study, we found VAT influences treatment response but not in a dose-dependent manner as previously hypothesized. If confirmed by future prospective studies, VAT may be employed as a biomarker to better inform treatment decisions and improve outcomes, especially considering the growth of artificial intelligence in medical imaging.

Background Inflammatory bowel disease (IBD) patients often continue to experience nonspecific gastrointestinal symptoms despite quiescent disease. Unlike non-IBD patients, IBD patients with dyssynergic defecation (DD) may present with various symptoms such as diarrhea, fecal incontinence, constipation, and rectal discomfort. Despite its importance and treatability, DD in IBD patients is not well recognized in practice. We conducted a systematic review and meta-analysis on the prevalence, diagnosis, and management of DD in IBD patients with ongoing defecatory symptoms. Methods We searched MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews (from 1966 through February 2017) to identify relevant studies on the prevalence, diagnostic methods, or management of DD in IBD patients with and without ileal pouch-anal anastomoses (IPAAs). A random effects model was used to calculate the pooled estimates with 95% confidence intervals (CIs). Heterogeneity was assessed with I2 statistics, Cochran Q statistic, and sensitivity analyses. Results Seven studies (n = 442) were included. In patients with ongoing defecatory symptoms, the prevalence of DD without IPAA ranged from 45% to 97%, and in patients with IPAA, it ranged from 25% to 75%. The prevalence of DD in IPAA patients with and without pouchitis ranged from 17% to 67% and 29% to 50%, respectively. The pooled response rate to biofeedback therapy in patients without IPAA was 70% (95% CI, 55%-84%; I2 = 95%; P < 0.01), and it was 86% (95% CI, 67%-98%; I2 = 61%; P = 0.05) in those with IPAA. Conclusions Despite limited data, the current literature suggests that DD is highly prevalent in active or quiescent IBD patients with ongoing defecatory symptoms and is responsive to biofeedback therapy. Although more studies are needed, DD should be considered in IBD patients with persistent defecatory symptoms.

Inflammatory bowel diseases (IBD) are associated with significant morbidity and economic burden. The variable course of IBD creates a need for predictors of clinical outcomes and health resource utilization (HRU) to guide treatment decisions. We aimed to identify clinical, serological or genetic markers associated with inpatient resource utilization in patients with ulcerative colitis (UC) and Crohn's disease (CD).Patients with IBD with available genetic and serological data who had at least one emergency department visit or hospitalization in a 3-year period were included. The primary outcome measure was HRU, as measured by the All Patient Refined Diagnosis Related Group classification system. Univariate and multivariate linear and logistic regression models were used to identify the associations with HRU.Altogether 858 (562 CD and 296 UC) patients were included. Anti-CBir1 seropositivity (P = 0.002, effect size [ES]: 0.762, 95% confidence interval [CI] 0.512-1.012) and low socioeconomic status (P = 0.005, ES: 1.620 [95% CI 1.091-2.149]) were independently associated with a high HRU. CD diagnosis (P = 0.006, ES: -0.701 [95% CI -0.959 to -0.443]) was independently associated with a low inpatient HRU.In patients with IBD who required at least one emergency department visit or hospitalization, anti-CBir1 antibody status may be a useful biomarker of HRU when formulating management strategies to reduce disease complications and resource utilization.

Bipolar disorder is associated with high rates of substance use disorders. However, few treatment trials are reported in this population. The goal of this pilot study was to obtain randomized, placebo-controlled data on quetiapine in bipolar disorder and cocaine dependence. Twelve outpatients with bipolar disorder and cocaine dependence were randomized to 12 weeks of quetiapine or placebo as add-on therapy. Participants were titrated within one week to 400 mg/day with flexible titration to a maximum of 800 mg/day. Cocaine and other substance use, craving, mood symptoms, and safety/tolerability were assessed. No significant between-group differences were observed in cocaine use or craving. The quetiapine group had significantly fewer heavy drinking days than the placebo group and showed a trend toward longer treatment retention. Significant between-group differences in mood measures were not observed, although differences in depression scores, favoring quetiapine, showed a large effect size. Other than con...

Objective Elevated serum levels of the amino acid homocysteine (HCY) are associated with a variety of diseases. To resolve conflicting findings in studies that suggest a relationship between elevated serum HCY levels and depression, we examined the relationship between HCY levels and depressive symptoms in the largest sample studied to date. Method We conducted a cross-sectional study of 11,757 participants (68.9% men) aged 20 to 90 years who completed preventive health examinations at the Cooper Clinic, Dallas, Texas, from 2007 to 2010. Currently experiencing depression was defined as a 10-item Center for Epidemiologic Studies Depression Scale (CES-D) score of ≥ 10. Serum HCY levels were obtained. Data were analyzed in a multiple logistic regression model of CES-D score of ≥ 10. Results When controlling for age, sex, body mass index, exercise, education, smoking, antidepressant use, creatinine level, alcohol use, and chronic medical conditions, elevated HCY was associated with 26% greater odds of currently experiencing depressive symptoms (P = .007) as defined by CES-D score. Conclusions In the largest sample examined to date, we found a significant positive relationship between elevated serum HCY levels and currently experiencing depressive symptoms. Given the cross-sectional nature of the study, it is not possible to determine the direction of the relationship or whether lowering HCY levels will ameliorate depressive symptoms. Thus, longitudinal studies are needed.