After Surgically Induced Remission, Ileal and Colonic Mucosa-Associated Microbiota Predicts Crohn's Disease Recurrence.

BACKGROUND & AIMS: Investigating the tissue-associated microbiota after surgically induced remission may help to understand the mechanisms initiating intestinal inflammation in Crohn's disease. METHODS: Patients with Crohn's disease undergoing ileocolic resection were prospectively recruited in 6 academic centers. Biopsy samples from the neoterminal ileum, colon, and rectosigmoid were obtained from colonoscopies performed after surgery. Microbial DNA was extracted for 16S rRNA gene sequencing. Microbial diversity and taxonomic differential relative abundance were analyzed. A random forest model was applied to analyze the performance of clinical and microbial features to predict recurrence. A Rutgeerts score ≥i2 was deemed as endoscopic recurrence. RESULTS: A total of 349 postoperative colonoscopies and 944 biopsy samples from 262 patients with Crohn's disease were analyzed. Ileal inflammation accounted for most of the explained variance of the ileal and colonic mucosa-associated microbiota. Samples obtained from 97 patients who were in surgically induced remission at first postoperative colonoscopy who went on to develop endoscopic recurrence at second colonoscopy showed lower diversity and microbial deviations when compared with patients who remained in endoscopic remission. Depletion of genus Anaerostipes and increase of several genera from class Gammaproteobacteria at the 3 biopsy sites increase the risk of further recurrence. Gut microbiome was able to predict future recurrence better than clinical features. CONCLUSIONS: Ileal and colonic mucosa-associated microbiome deviations precede development of new-onset ileal inflammation after surgically induced remission and show good predictive performance for future recurrence. These findings suggest that targeted microbial modulation is a plausible modality to prevent postoperative Crohn's disease recurrence.

Epithelioid Granulomas Associate With Increased Severity and Progression of Crohn's Disease, Based on 6-Year Follow-Up.

BACKGROUND & AIMS: Epithelioid granulomas are characteristics of a subset of patients with Crohn's disease (CD), but their significance, with regard to disease progression and severity, is unclear. We investigated the relationship between granulomas and CD severity over a 6-year time period in a large cohort of patients. METHODS: We performed a retrospective study of patients with CD seen at the Inflammatory Bowel Disease Center at the University of Pittsburgh; data were collected from 2009 through 2014 and patients were assigned to groups with and without histologic evidence of granuloma. Demographic, clinical (including disease activity, quality of life, medication use, and healthcare utilization), and laboratory data were used in association and survival analyses. Differences between groups were evaluated using the Mann-Whitney U-test for continuous variables. RESULTS: Of 1466 patients with CD, granulomas were identified in 187 (12.8%). In the subset of patients who underwent surgery, 21.0% had granulomas. The presence of granuloma was associated with increased serum levels of c-reactive protein (odds ratio [OR], 2.9; 95% CI, 2.078-4.208; P < .0001), younger mean age at diagnosis (23.6 ± 11.3 years in patients with granulomas vs 27.9 ± 13.3 years in patients without; P = .0005), higher rates of stricturing or penetrating disease phenotype, higher rates of steroid and narcotic use, and higher healthcare utilization. Among patients that underwent surgery, the presence of granulomas was associated with need for repeat surgery during the 6-year observation period (OR, 2.5; 95% CI, 1.54-4.02; P = .0002). Infliximab use was associated with detection of granuloma in a significantly lower proportion of surgical specimens compared to patients who had not been treated with a biologic agent (OR, 0.22; 95 CI, 0.05-0.97; P = .03). CONCLUSIONS: Epithelioid granulomas develop in less than 13% of patients with CD, and are associated with a more aggressive disease phenotype. Patients who have undergone surgery for CD and have granulomas are at increased risk for repeat surgery within 6 years.

Ileocecal Anastomosis Type Significantly Influences Long-Term Functional Status, Quality of Life, and Healthcare Utilization in Postoperative Crohn's Disease Patients Independent of Inflammation Recurrence.

OBJECTIVES: Anastomotic reconstruction following intestinal resection in Crohn's disease (CD) may employ side-to-side anastomosis (STSA; anti-peristaltic orientation) or end-to-end anastomosis (ETEA). Our aim was to determine the impact of these two anastomotic techniques on long-term clinical status in postoperative CD patients. METHODS: We performed a comparative effectiveness study of prospectively collected observational data from consented CD patients undergoing their first or second ileocolonic bowel resection and re-anastomosis between 2008 and 2012, in order to assess the association between anastomosis type and 2-year postoperative quality of life (QoL), healthcare utilization, disease clinical or endoscopic recurrence, use of medications, and need for repeat resection. RESULTS: One hundred and twenty eight postoperative CD patients (60 STSA and 68 ETEA) were evaluated. At 2 years postoperatively, STSA patients had higher rates of emergency department visits (33.3% vs. 14.7%; P=0.01), hospitalizations (30% vs. 11.8%; P=0.01), and abdominal computed tomography scans (50% vs. 13.2%; P<0.001) with lower QoL (mean short inflammatory bowel disease questionnaire 47.9 vs. 53.4; P=0.007). There was no difference among the two groups in the 30 day surgical complications and 2-year patterns of disease activity, CD medication requirement, endoscopic recurrence, and need for new surgical management (all P > 0.05). CONCLUSIONS: At 2 years postoperatively, CD patients with ETEA demonstrated better QoL and less healthcare utilization compared with STSA, despite having similar patterns of disease recurrence and CD treatment. These findings suggest that surgical reconstruction of the bowel as an intact tube (ETEA) contribute to improved functional and clinical status in patients with CD.

Telephone Encounters Predict Future High Financial Expenditures in Inflammatory Bowel Disease Patients: A 3-Year Prospective Observational Study.

BACKGROUND: Telephone activity is essential in management of complex chronic diseases including inflammatory bowel disease (IBD). Telephone encounters logged in the electronic medical record have recently been proposed as a surrogate marker of disease activity and impending health care utilization; however, the association between telephone calls and financial expenditures has not been evaluated. STUDY: We performed a 3-year prospective observational study of telephone encounters logged at a tertiary referral IBD center. We analyzed patient demographics, disease characteristics, comorbidities, clinical activity, and health care financial charges by telephone encounter frequency. RESULTS: Eight hundred one patients met inclusion criteria (52.3% female; mean age, 44.1 y), accounted for 12,669 telephone encounters, and accrued $70,513,449 in charges over 3 years. High telephone encounter frequency was associated with female gender (P=0.003), anxiety/depression (P<0.001), and prior IBD surgery (P<0.001). High telephone encounter categories had significantly more hospitalizations (P<0.001), IBD surgery (P<0.001), worse quality of life (P<0.001), more corticosteroid (P<0.001), biological (P<0.001), and opiate prescriptions (P<0.001). High telephone encounter frequency patients amassed higher total available charges in each year (P<0.001) and over the 3 years (P<0.001). Telephone encounters in 2009 (P=0.02) and 2010 (P<0.001) were significantly associated with financial charges the following year after controlling for demographic, utilization, and medication covariates. CONCLUSIONS: Increased telephone encounters are associated with significantly higher health care utilization and financial expenditures. Increased call frequency is predictive of future health care spending. Telephone encounters are a useful tool to identify patients at risk of clinical deterioration and large financial expense.

Low Rates of Dermatologic Care and Skin Cancer Screening Among Inflammatory Bowel Disease Patients.

BACKGROUND: Dermatologic manifestations of inflammatory bowel disease (IBD) are common, and certain IBD medications increase the risk of skin cancer. AIMS: To define the rates of care and factors associated with dermatologic utilization with a focus on skin cancer screening. METHODS: We utilized a prospective, natural history IBD research registry to evaluate all outpatient healthcare encounters from 2010 to 2016. Gastrointestinal, dermatologic and primary care visits per individual were identified. We calculated the proportion of patients obtaining care, categorized primary indications for dermatologic visits, determined the incidence of melanoma and non-melanoma skin cancers, and used logistic regression to determine factors associated with dermatology utilization. RESULTS: Of the 2127 IBD patients included, 452 (21.3%) utilized dermatology over the study period, and 55 (2.6%) had a total body skin examination at least once. The 452 patients incurred 1633 dermatology clinic visits, 278 dermatologic procedures, and 1108 dermatology telephone encounters. The most frequent indication was contact dermatitis or dermatitis. Factors associated with dermatology use were family history of skin cancer, employment, systemic steroids, longer disease duration, emergency room use, and the number of IBD-related clinic visits. Between 8.3 and 11% of IBD patients recommended for skin cancer screening visited dermatology each year, and the resulting incidence of non-melanoma skin cancer was 35.4/10,000 [95% CI 23.3-51.5] and melanoma was 6.56/10,000 [95% CI 2.1-15.3]. CONCLUSIONS: Less than one in ten IBD patients obtain dermatologic care. Given the increased risk of skin cancers among IBD patients, an emphasis on education, prevention, and screening merits attention.

Peripheral Eosinophilia in Patients With Inflammatory Bowel Disease Defines an Aggressive Disease Phenotype.

OBJECTIVES: Peripheral blood eosinophilia (PBE) in inflammatory bowel disease (IBD) is associated with ulcerative colitis (UC) and active disease. Little data exist on the long-term impact of PBE on disease course. We aimed to investigate the multi-year patterns of PBE and its impact on disease severity in a large IBD cohort. METHODS: We performed a registry analysis of a consented, prospective, natural history IBD cohort at a tertiary center from 2009 to 2014. Demographics, comorbidities, disease activity, healthcare utilization, and time to hospitalization or surgical resection of patients who displayed PBE were compared to patients without PBE. RESULTS: Of the 2,066 IBD patients, 19.2% developed PBE. PBE was significantly associated with UC (P<0.001), extensive colitis (P<0.001), and shorter disease duration (P=0.03). Over six years, PBE patients had more active disease (Harvey-Bradshaw Index P=0.001; ulcerative colitis activity index P<0.001), concurrent C-reactive protein elevation (P<0.001), healthcare utilization (hospitalization P<0.001, IBD surgery P<0.001), and more aggressive medical therapy (prednisone P<0.001, anti-TNF P<0.001). Patients with PBE had a significantly reduced time to hospitalization in both UC (P<0.001) and Crohn's disease (CD) (P<0.001) and reduced time to colectomy in UC (P=0.003). On multivariable modeling, PBE remained significantly associated with hospitalization and surgery in both CD and UC. New diagnosis of UC with PBE was associated with increased steroid (P=0.007) and anti-TNF (P=0.001) requirement. CONCLUSION: This multi-year study of a large IBD cohort suggests that peripheral blood eosinophilia represents a biomarker of a distinct IBD subgroup, with a unique inflammatory signature, and at risk for worse clinical outcomes.

Association of Vitamin D Level With Clinical Status in Inflammatory Bowel Disease: A 5-Year Longitudinal Study.

OBJECTIVES: Emerging data suggest that vitamin D has a significant role in inflammatory bowel disease (IBD). Prospective data evaluating the association of vitamin D serum status and disease course are lacking. We sought to determine the relationship between vitamin D status and clinical course of IBD over a multiyear time period. METHODS: IBD patients with up to 5-year follow-up from a longitudinal IBD natural history registry were included. Patients were categorized according to their mean serum 25-OH vitamin D level. IBD clinical status was approximated with patterns of medication use, health-care utilization, biochemical markers of inflammation (C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)), pain and clinical disease activity scores, and health-related quality of life. RESULTS: A total of 965 IBD patients (61.9% Crohn's disease, 38.1% ulcerative colitis) formed the study population (mean age 44 years, 52.3% female). Among them, 29.9% had low mean vitamin D levels. Over the 5-year study period, subjects with low mean vitamin D required significantly more steroids, biologics, narcotics, computed tomography scans, emergency department visits, hospital admissions, and surgery compared with subjects with normal mean vitamin D levels (P<0.05). Moreover, subjects with low vitamin D levels had worse pain, disease activity scores, and quality of life (P<0.05). Finally, subjects who received vitamin D supplements had a significant reduction in their health-care utilization. CONCLUSIONS: Low vitamin D levels are common in IBD patients and are associated with higher morbidity and disease severity, signifying the potential importance of vitamin D monitoring and treatment.

Delineation of Crohn's Disease Trajectories Using Change in Lémann Index: A Natural History Study.

BACKGROUND: Crohn's disease (CD) causes lifelong, progressive bowel damage, which may be quantified using the Lémann Index (LI). We aimed to analyze patterns of LI and its association with 5-year clinical course, in an independent cohort of CD patients. METHODS: CD patients with 5-year follow-up from a registry maintained at a tertiary center were included. LI was calculated using a computerized metric from the first (LI1) and last (LI2) clinical encounters during the 5 years. Groups were created based on change in score (LI2-LI1) or the delta Lémann Index (DLI) as showing improvement, no change, or deterioration and used for association analysis with patterns of health care utilization, disease activity, and quality-of-life scores. RESULTS: A total of 363 CD patients with 5-year follow-up formed the study population [median age 43 y (interquartile range (IQR), 33.3 to 55 y); 57% female; median disease duration 12 y (IQR, 3 to 19 y), overall surgical exposure 69.7%]. Median (IQR) LI1, LI2, and DLI were 8 (0 to 54), 9 (0 to 75), and 0 (-22 to -47), respectively. Patients were stratified based on DLI into 3 groups: A: DLI<0; B: DLI=0; and C: DLI>0; which comprised 16.5%, 35.3%, and 48.2% of the cohort, respectively. Patients in group C had significantly higher CD-related surgical exposure, health care utilization, and annual use of steroids and biological agents. DLI showed independent significant positive correlation with perianal disease (P=0.044), steroid use (P=0.007), clinical visits (P<0.001), and new surgeries (P=0.001). CONCLUSIONS: Change in LI over time could function as a marker of disease trajectory for risk substratification and prognostication in CD.

Five-Year Period Prevalence and Characteristics of Anemia in a Large US Inflammatory Bowel Disease Cohort.

BACKGROUND: Anemia is a common manifestation of inflammatory bowel disease (IBD), but its prevalence in the United States is not well defined. Aim of this study was to determine the prevalence and characteristics of anemia in IBD patients who were followed in a US referral center. MATERIALS AND METHODS: Demographic, clinical, laboratory, and treatment data from a prospective, consented longitudinal IBD registry between the years 2009 and 2013 were analyzed. Disease activity was evaluated using Harvey-Bradshaw index in Crohn's disease (CD) and ulcerative colitis (UC) activity index in UC as well as C-reactive protein and erythrocyte sedimentation rate. Anemia was defined based on the World Health Organization criteria. RESULTS: A total of 1821 IBD patients (1077 with CD, 744 with UC, median age 43.8 y, 51.9% female) were included. The 5-year period prevalence of anemia in IBD patients was 50.1%, (CD: 53.3% vs. UC: 44.7%, P=0.001). In multivariate logistic regression analysis, anemia was associated with surgery for IBD [odds ratio (OR)=2.77; 95% confidence interval (CI), 2.21-3.48; P<0.0001], female gender (OR=1.29; 95% CI, 1.04-1.61; P=0.02), C-reactive protein (OR=1.26; 95% CI, 1.16-1.37; P<0.0001), erythrocyte sedimentation rate (OR=1.02; 95% CI, 1.01-1.03; P=0.0002), and use of biologics (OR=2.00; 95% CI, 1.58-2.52; P=0.0001) or immunomodulators (OR=1.51; 95% CI, 1.21-1.87; P=0.0003). Iron replacement therapy was administered to 46.8% of the anemic patients. CONCLUSION: Anemia has a high period prevalence in IBD patients followed at a tertiary center. Anemia is more common in CD than in UC, is associated with disease activity, and in current practice is undertreated.

Association Between Long-Term Lipid Profiles and Disease Severity in a Large Cohort of Patients with Inflammatory Bowel Disease.

BACKGROUND: Inflammatory bowel disease (IBD) has been linked to an increased risk of coronary heart disease and stroke. Dyslipidemia is a well-established risk factor for cardiovascular disease. The aim of this study was to investigate the long-term lipid profiles in a large cohort of IBD patients. METHODS: Data of patients from an IBD registry who had more than one measurement of total cholesterol and triglyceride levels during the follow-up period were analyzed. The lipid profiles of IBD patients were compared to those of the general population according to National Health and Nutrition Examination Survey (2009-2012). Quartiles of cholesterol or triglyceride levels in relation to surrogate markers of disease severity were analyzed. RESULTS: Seven hundred and one IBD patients [54% Crohn's disease (CD), 46% ulcerative colitis (UC)] were included. IBD patients had less frequent high total cholesterol and high LDL cholesterol (6 vs. 13 and 5 vs. 10%) and more frequent low HDL and high triglycerides (24 vs. 17 and 33 vs. 25%) compared to the general population (all p < 0.001). Median total cholesterol levels were lower and median triglycerides higher in CD compared to UC (171 vs. 184; 123 vs. 100 mg/dL; both p < 0.001). In the multiple regression analysis, lipid profile was independently associated with hospitalizations (low cholesterol) and IBD surgeries (low cholesterol and high triglycerides). CONCLUSIONS: Low total cholesterol and high triglyceride levels are more frequent in IBD patients (in particular CD) compared to healthy controls and are independently associated with more severe disease.

Development of an Inflammatory Bowel Disease Research Registry Derived from Observational Electronic Health Record Data for Comprehensive Clinical Phenotyping.

BACKGROUND: Inflammatory bowel disease (IBD) is a heterogeneous collection of chronic inflammatory disorders of the digestive tract. Clinical, genetic, and pathological heterogeneity makes it increasingly difficult to translate efficacy studies into real-world practice. Our objective was to develop a comprehensive natural history registry derived from multi-year observational data to facilitate effectiveness and clinical phenotypic research in IBD. METHODS: A longitudinal, consented registry with prospectively collected data was developed at UPMC. All adult IBD patients receiving care at the tertiary care center of UPMC are eligible for enrollment. Detailed data in the electronic health record are accessible for registry research purposes. Data are exported directly from the electronic health record and temporally organized for research. RESULTS: To date, there are over 2565 patients participating in the IBD research registry. All patients have demographic data, clinical disease characteristics, and disease course data including healthcare utilization, laboratory values, health-related questionnaires quantifying disease activity and quality of life, and analytical information on treatment, temporally organized for 6 years (2009-2015). The data have resulted in a detailed definition of clinical phenotypes suitable for association studies with parameters of disease outcomes and treatment response. We have established the infrastructure required to examine the effectiveness of treatment and disease course in the real-world setting of IBD. CONCLUSIONS: The IBD research registry offers a unique opportunity to investigate clinical research questions regarding the natural course of the disease, phenotype association studies, effectiveness of treatment, and quality of care research.

Persistent or Recurrent Anemia Is Associated With Severe and Disabling Inflammatory Bowel Disease.

BACKGROUND & AIMS: Anemia is a common manifestation of inflammatory bowel disease (IBD) that can greatly affect patients' quality of life. We performed a prospective study of a large cohort of patients with IBD to determine if patterns of anemia over time are associated with aggressive or disabling disease. METHODS: We performed a longitudinal analysis of demographic, clinical, laboratory, and treatment data from a registry of patients with IBD at the University of Pittsburgh Medical Center from 2009 through 2013. Patients with a complete follow-up evaluation (at least 1 annual visit with laboratory results) were included. Anemia was defined by World Health Organization criteria. Disease activity scores (the Harvey-Bradshaw Index or the ulcerative colitis activity index) and quality-of-life scores (based on the short IBD questionnaire) were determined at each visit; laboratory data, including levels of C-reactive protein and erythrocyte sedimentation rates, as well as patterns of IBD-related health care use, were analyzed. RESULTS: A total of 410 IBD patients (245 with Crohn's disease, 165 with ulcerative colitis; 50.5% female) were included. The prevalence of anemia in patients with IBD was 37.1% in 2009 and 33.2% in 2013. Patients with IBD and anemia required significantly more health care and had higher indices of disease activity, as well as a lower average quality of life, than patients without anemia (P < .0001). Anemia (persistent or recurrent) for 3 or more years was correlated independently with hospitalizations (P < .01), visits to gastroenterology clinics (P < .001), telephone calls (P < .004), surgeries for IBD (P = .01), higher levels of C-reactive protein (in patients with ulcerative colitis, P = .001), and a higher erythrocyte sedimentation rate (P < .0001). Anemia was correlated negatively with quality-of-life scores (P < .03). CONCLUSIONS: Based on a longitudinal analysis of 410 patients, persistent or recurrent anemia correlates with more aggressive or disabling disease in patients with IBD.

Association between telephone activity and features of patients with inflammatory bowel disease.

BACKGROUND & AIMS: Telephone communication is common between healthcare providers and patients with inflammatory bowel disease (IBD). We analyzed telephone activity at an IBD care center to identify disease and patient characteristics associated with high levels of telephone activity and determine if call volume could identify individuals at risk for future visits to the emergency department (ED) or hospitalization. METHODS: We performed a prospective observational study in which we categorized telephone calls received by nursing staff over 2 years at a tertiary care IBD clinic (2475 patients in 2009 and 3118 in 2010). We analyzed data on 21,979 ingoing and outgoing calls in 2009 and 32,667 calls in 2010 and assessed associations between clinical factors and logged telephone encounters, and between patterns of telephone encounters and future visits to the ED or hospitalization. RESULTS: Telephone encounters occurred twice as frequently as office visits; 15% of the patients generated >10 telephone encounters per year and were responsible for half of all telephone encounters. A higher percentage of these high telephone encounter (HTE) patients were female, had Crohn's disease, received steroid treatment, had increased levels of C-reactive protein and rates of erythrocyte sedimentation, had psychiatric comorbidities, and had chronic abdominal pain than patients with lower telephone encounters. The HTE patients were also more frequently seen in the ED or hospitalized over the same time period and in subsequent years. Forty-two percent of patients with >8 telephone encounters within 30 days were seen in the ED or hospitalized within the subsequent 12 months. CONCLUSIONS: Based on an analysis of telephone records at an IBD clinic, 15% of patients account for half of all calls. These HTE patients are a heterogeneous group with refractory disease who are likely to visit the ED or be hospitalized.

Efficacy of Ustekinumab and Vedolizumab Among Postoperative Crohn's Disease Patients as Postoperative Prophylaxis and Rescue Therapy: Real-world Data.

BACKGROUND: Almost half of patients with Crohn's disease (CD) require bowel surgeries in their lifetime. Due to the high risk of postoperative disease recurrence and high rate of previous antitumor necrosis factor (anti-TNF) failure, often alternative therapy options such as ustekinumab (UST) and vedolizumab (VDZ) are used. We aimed to evaluate the efficacy of UST and VDZ among postoperative CD patients as postoperative prophylaxis and rescue therapy. METHODS: Consented CD patients who underwent initial ileocecal resection and were treated with UST and VDZ were included in this study. Demographics, clinical characteristics, health care utilization, endoscopy scores, and surgery outcomes were collected. Postoperative early CD recurrence was defined as a Rutgeerts endoscopic score ≥i2 within the first 2 years. The rescue therapy group was defined as patients who received either UST or VDZ after having Rutgeerts endoscopic score ≥i2 postoperatively. RESULTS: During 2009 to 2019, 98 CD patients were treated with UST or VDZ postoperatively. Postoperative early recurrence rates were 5% (n = 1 out of 20) and 6% (1 out of 15) for the UST and VDZ groups, respectively. Two patients from the UST group and 1 patient from the VDZ group required bowel surgery during follow-up with median drug exposure of 51 (95% confidence interval [CI], 29-61) and 30 (95% CI, 14-63) months, respectively; 55% and 69% of patients had at least 1 point of improvement on postoperative endoscopic Rutgeerts score, respectively, for UST and VDZ. Only 3 out of 40 and 1 out of 23 patients required bowel surgery during follow-up while receiving UST and VDZ as rescue therapy. CONCLUSIONS: Both UST and VDZ were effective as postoperative therapies either as prophylaxis or rescue therapy.

This retrospective 11-year data examines the efficacy of ustekinumab and vedolizumab among postoperative Crohn's disease patients. When utilizing postoperative Rutgeerts score, this study confirms that both ustekinumab and vedolizumab were effective as postoperative therapies either as prophylaxis or rescue therapy.

The IL17A and IL17F loci have divergent histone modifications and are differentially regulated by prostaglandin E2 in Th17 cells.

Prostaglandin E2 (PGE2), IL-23 and IL-1ß are implicated in inflammatory bowel disease susceptibility, likely in part by modulating IL-17 producing CD4(+) T helper (Th17) cells. To better understand how these three mediators affect Th17 cell memory responses, we characterized the gene expression profiles of activated human peripheral CD4(+) effector memory T cells and sorted Th17 memory cells from healthy donors concurrent with IL17A mRNA induction mediated by PGE2 and/or IL-23 plus IL-1ß. We discovered that PGE2 and IL-23 plus IL-1ß differentially regulate Th17 cytokine expression and synergize to induce IL-17A, but not IL-17F. IL-23 plus IL-1ß preferentially induce IL-17F expression. The addition of PGE2 to IL-23 plus IL-1ß only enhances IL-17A expression as mediated by the PGE2 EP4 receptor, and promotes a switch from an IL-17F to an IL-17A predominant immune response. The human Th17 HuT-102 cell line was also found to constitutively express IL-17A, but not IL-17F. We went on to show that the IL17A and IL17F loci have divergent epigenetic architectures in unstimulated HuT-102 and primary Th17 cells and are poised for preferential expression of IL17A. We conclude that the chromatin for IL17A and IL17F are distinctly regulated, which may play an important role in mucosal health and disease.

Recurrent blood eosinophilia in ulcerative colitis is associated with severe disease and primary sclerosing cholangitis.

BACKGROUND AND AIMS: Eosinophils are implicated in the pathogenesis of inflammatory bowel disease (IBD). A subset of IBD patients develops blood eosinophilia, and the clinical profile of these patients is undefined. We sought to characterize IBD patients with and without eosinophilia. METHODS: We studied a prospective registry of 1,176 IBD patients followed in a tertiary referral center. Patients who developed eosinophilia at any time were identified by electronic medical record query. We performed a chart review case-control study comparing patients with recurrent eosinophilia versus randomly selected disease-matched patients with no history of eosinophilia. Histological analysis was performed on selected cases and controls. RESULTS: Eosinophilia at any time was more prevalent in ulcerative colitis (UC) patients than Crohn's disease patients (22.2 versus 12.7%), as was recurrent eosinophilia (3.4 versus 0.7%). UC patients with recurrent eosinophilia were predominantly male compared with the control UC population (81.3 versus 46.9%) and had higher rates of colectomy for either medically refractory disease or dysplasia/cancer than control UC patients (56.3 versus 15.6%). Primary sclerosing cholangitis (PSC) occurred in 37.5% of UC patients with recurrent eosinophilia compared with only 3.1% in the UC controls. Histological analysis of random diagnostic samples from UC patients with recurrent eosinophilia demonstrated a normal eosinophil pattern as seen in the control UC population. CONCLUSIONS: Eosinophilia-associated UC is a subgroup of IBD associated with severe colitis and PSC. Further studies are warranted to characterize molecular mechanisms underlying eosinophilia-associated UC and to determine optimal approaches for therapy.

A Safe and Novel Outpatient Subcutaneous Vitamin B12 Desensitization Protocol in A Patient with Crohn's Disease and Vitamin B12 Allergy: A Case Report.

INTRODUCTION: Although rare, some patients may have a vitamin B12 allergy. Crohn's disease commonly leads to significant vitamin B12 deficiency, especially in those patients that have undergone ileal resection. In these difficult cases, vitamin B12 desensitization may be required. CASE PRESENTATION: Here, we report a successful case of a serial outpatient subcutaneous vitamin B12 desensitization protocol in a 35-year-old female with a past medical history of Crohn's disease status post ileal resection, subsequent vitamin B12 deficiency, and allergy to subcutaneous vitamin B12. CONCLUSION: This is the first subcutaneous vitamin B12 desensitization protocol reported to have been safely performed in the outpatient setting.

Granuloma Presence at Initial Surgery Predicts Need for Repeat Surgery Independent of Rutgeerts Score in Crohn's Disease.

BACKGROUND: Approximately half of Crohn's disease (CD) patients experience recurrence and need for repeat resections, highlighting need for prognostic biomarkers. Presence of epithelioid granuloma on surgical tissue and high Rutgeerts endoscopic score are associated with postoperative CD clinical recurrence. We sought to evaluate presence of epithelioid granuloma at first surgery and Rutgeerts score as a combined risk assessment for CD surgical recurrence. METHODS: Our study included consented CD patients who underwent initial ileocecal resection and were prospectively followed postoperatively. From 2009 to 2019, 418 CD patients underwent initial ileocecal resection with >4 years of follow-up, including postoperative endoscopic assessment (Rutgeerts score). RESULTS: Postoperative CD patients were grouped based on granuloma presence (30.6%; n = 128) or absence (69.4%; n = 290). Endoscopic recurrence (defined as Rutgeerts score ≥i2) was similar between the granuloma (26%) and no granuloma (25%) groups, respectively (P = .82). Patients with granuloma and CD endoscopic recurrence at first postoperative endoscopy had higher number of bowel surgeries compared with all other groups (no granuloma or CD endoscopic recurrence, P = .007; no granuloma but CD endoscopic recurrence present, P = .04; granuloma present and no CD endoscopic recurrence, P = .04). Epithelioid granuloma presence was associated with 1.65 times higher risk of subsequent surgery independently from first postoperative endoscopic recurrence Rutgeerts score. CONCLUSIONS: Granuloma presence on initial surgical histology is immediately available and identifies high-risk CD patients who may benefit from early postoperative treatment, and these precision intervention trials are warranted.

This study shows the presence of epithelioid granuloma as a risk factor for repeat Crohn's disease­related surgery, which is independent of first postoperative Rugteerts score. These 11-year observational data provide a risk factor that is immediately available after surgery and identifies high-risk CD patients who may benefit from early postoperative treatment.

Geriatric inflammatory bowel disease: phenotypic presentation, treatment patterns, nutritional status, outcomes, and comorbidity.

BACKGROUND AND AIMS: The U.S. population is aging and the burden of geriatric inflammatory bowel disease (IBD) patients has increased. Systematic data describing phenotypic presentation, treatment regimens, outcomes and comorbidities in elderly IBD patients is limited. We performed a retrospective observational study of IBD patients age ≥65 followed in a 20-hospital system to determine patterns of phenotypic presentation, treatment, polypharmacy, nutritional status and comorbidity. METHODS: Data were extracted from electronic medical record based on ICD-9 coding/indexed terms on Crohn's disease (CD) and ulcerative colitis (UC) patients. RESULTS: A total of 393 geriatric IBD patients were identified (49.1% males; 50.9% females; 61.8% UC; 38.2% CD; 73.4 ± 6.6 years old). Younger age at diagnosis of CD (≤64) was associated with greater prevalence of small bowel surgeries (63.6%) compared with those diagnosed after age ≥65 (20.9%) (p < 0.005). Fistulizing/penetrating disease was frequent in patients diagnosed with CD at a younger age (43.6% compared to 7%) (p < 0.005). IBD maintenance treatment included: 44% 5-ASA agents; 31.6% maintenance prednisone (defined as ≥6 months treatment duration); 4.8% steroid suppositories; 5.6% 6MP/azathioprine; 1.3% methotrexate; 1.3% adalimumab; 1.3% infliximab; 9.4% loperamide/diphenoxylate/atropine; 0.5% had no IBD medications. Longer duration of CD disease correlated with vitamin B12, vitamin D and iron deficiency. CONCLUSION: Geriatric patients diagnosed with CD earlier in life had greater small bowel involvement compared with new onset geriatric CD. There is low utilization of immunomodulator and biologic agents in geriatric IBD patients. Duration of CD correlates with nutrient deficiency. Prospective studies are warranted in this respect.

High Sugar-Sweetened Beverage Consumption Is Associated with Increased Health Care Utilization in Patients with Inflammatory Bowel Disease: A Multiyear, Prospective Analysis.

BACKGROUND: Dietary factors like sugar-sweetened beverage (SSB) consumption are known to influence disease course in a variety of illnesses; however, long-term outcomes are not well documented for inflammatory bowel disease. OBJECTIVE: Does high consumption of SSBs lead to high healthcare utilization (ie, hospitalizations and emergency department visits), inflammation, and disease severity in patients with inflammatory bowel disease? DESIGN: A prospective cohort study was conducted from 2015 to 2019. Patients enrolled in the discovery study cohort were followed for 3 years, whereas patients in the validation cohort were followed for 2 years. They underwent nutrition assessment and received routine care. Dietary intakes of SSBs and fiber were quantified by a validated, self-reported questionnaire. PARTICIPANTS/SETTING: For the discovery study cohort, 1133 adult patients were recruited from the University of Pittsburgh Medical Center Digestive Disease Clinic in Pittsburgh, PA. Eligible patients had a preexisting diagnosis of Crohn's disease or ulcerative colitis and had at least annual follow-up at this tertiary referral center. High SSB consumption was defined as 7 or more SSBs per week. Moderate was defined as > 2 but < 7 SSBs per week. Low SSB consumption was defined as 2 or fewer SSBs per week. MAIN OUTCOME MEASURES: Primary outcome was time to hospitalization and emergency department visits. Secondary outcomes assessed laboratory markers of disease severity and inflammation. Tertiary outcomes assessed time to hospitalization and emergency department visits in a subsequent independent cohort of patients. STATISTICAL ANALYSIS PERFORMED: Multivariable logistic regression, Kaplan-Meier, and Cox proportional hazards modeling RESULTS: The discovery cohort included of 1,133 adult patients with inflammatory bowel disease (58% women, 70% with Chron's disease, 30% with ulcerative colitis, median age 46 years). Low SSB consumption, moderate SSB consumption, and high SSB consumption occurred in 57%, 17%, and 26% in the discovery cohort, respectively. Among patients without active disease at enrollment, high SSB consumption was associated with decreased time to hospitalization and emergency department visits when compared with low SSB consumption (hazard ratio 1.55, 95% CI 1.06 to 2.27; and hazard ratio 1.53, 95% CI 1.10 to 2.13). In terms of disease severity and inflammatory biomarkers, high SSB consumption was associated with increase odds of elevated erythrocyte sedimentation rate (odds ratio 2.04, 95% CI 1.31 to 3.18), elevated C-reactive protein level (odds ratio 1.60, 95% CI, 1.07-2.37), eosinophilia (odds ratio 1.88, 95% CI 1.06 to 3.335), and monocytosis (odds ratio 1.81, 95% CI 1.18 to 2.79) when compared with low SSB consumption after adjusting for baseline differences. Lastly, the validation cohort produced similar results to our primary outcome (ie, high SSB consumption was associated with decreased time to hospitalization and emergency department visits when compared with low SSB consumption). CONCLUSIONS: High SSB consumption was associated with decreased time to hospitalization and emergency department visits. Furthermore, high SSB consumption is associated with disease severity biomarkers and inflammation. Prospective studies assessing the therapeutic influence of nutrition counseling and decreased SSB consumption on long-term inflammatory bowel disease clinical course are warranted.